Behind the Genes

In this explainer episode, we’ve asked Mathilde Leblond, Senior Design Researcher for the Generation Study at Genomics England, to answer some frequently asked questions that we received from parents who we engaged with for the design of the study.

You can hear more information about Generation Study via the study's official website and in our previous podcast episodes:

• How has design research shaped the Generation Study?

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

If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on [email protected].

You can download the transcript or read it below.

Naimah: You may have heard about the Generation Study. This research study led by Genomics England in partnership with NHS England will sequence the whole genomes of a hundred thousand newborn babies and will look for more than 200 rare conditions that could be treated in the NHS in early childhood. 

The study seeks to improve how we diagnose and treat rare genetic conditions to enable babies and families to have better outcomes. Today I'm joined by Mathilde Leblond, who leads design research for the Generation Study, and will be answering some of the frequently asked questions that we receive from parents who we engaged with for the design of the study — the same questions that expectant parents at participating hospitals might have before deciding if they want to take part. 

So first of all, Mathilde, can you tell me a little bit more about your role? 

Mathilde: Hello. So, I'm a design researcher. My role is to support my colleagues, understand our users deeply so that we can create experiences that are as positive and seamless as possible. 

So today we'll talk about the parents who are the ones invited to take part in the Generation Study, but our users also include the midwives who are approaching them and taking blood samples. The clinical scientists who are interpreting the results and the specialist paediatricians will be contacting the parents if a condition is suspected, and even many more users actually. 

So, we did a lot of research prior to launching to shape the Generation Study, and now that we're live, we continue doing more to keep improving the experience. 

Naimah: Okay, so can you give us a bit of background? How did you engage with parents in this study? 

Mathilde: Yeah, so today we've involved over 150 pregnant and recent parents in our co-design sessions. 

And these sessions were slightly different each time with different topics and exercises, but generally we spend around 90 minutes with one parent. And we asked them to bring someone who helped them make decisions about their baby during their pregnancy. So that meant that we had their mums, their sisters, their husbands, their wives and friends as well, taking part and discussing the Generation Study with us. 

During that time with them, we would test our materials. We listened out to what's important to them and what they asked about, and we got them to show us what would work better for them so that we could then shape the materials around that.  

Naimah: So you can find out a bit more about why it's important to involve users in co-design in our podcast ‘How has design research helped shape the Generation Study?’, which is available on our website.  

So, we have a list of frequently asked questions from some of the parents, and I wanted to post some of them to you today, Mathilde. So first of all, one of the questions was, why should my baby take part in this study? 

Mathilde: Yeah, I mean, that's really the key questions that all parents are asking themselves before they even spend any time finding out more about the Generation Study. And our materials do reflect that. So what tends to matter most to the parents we spoke to, is that there's a small chance that their baby may benefit directly from taking part because if a condition is suspected, they'll be invited for further specialised tests within the NHS, and they could receive treatment much sooner than if we had waited for the symptoms to develop and for a diagnosis to come, which can sometimes take years for some rare conditions. But for a large majority of the babies, 99%, they will have no condition suspected and so their involvement really is more altruistic. Taking part means that their parents agree to share the baby's healthcare records on an ongoing basis and their genome with researchers who can then look at this together with information from thousands of other babies and patients to help improve our understanding of genes and health. 

So taking part in the Generation Study also means that you might help uncover some life-changing early treatments for babies in the future. And finally, something that's super important to us is that people from Black, Asian and other minority ethnic communities have historically been underrepresented in this type of research. So, we're working hard to make the Generation Study as inclusive as possible to help genetic testing and treatments be improved for everybody in the future. So, there's many reasons to take part in the Generation Study.  

Naimah: You mentioned the word altruistic there. Can you tell me what that means?  

Mathilde: Yeah, so that's really to help society. They may not get benefits within their own lives or within their own family, but somebody somewhere will benefit from it in the future. And that's what altruistic means.  

Naimah: Thank you. So, some parents might also ask, will this test tell me every illness that my baby might have now and in the future? 

Mathilde: No. So first of all, we're still learning a lot about how genes work, how the environment affects them, and there's also many conditions that we still don't understand very well. So those are not in. Of the conditions that we do understand quite well. We did a big piece of public engagement in 2022 to try and decide which ones to include as part of the screening. 

And while some parents told us that they would want to know every single thing in advance, a lot of parents were worried about how much it would raise their anxiety to find out about a potentially incurable condition at such a fragile and beautiful moment when you have a new baby. So, for this reason and many other reasons, we've decided to proceed really cautiously so that the conditions that we'll be testing for have been chosen to reflect 4 key principles. And you can find them on the website. But the main gist is that we'll only be looking for conditions that normally start in childhood, first few years of life. So, nothing around Alzheimer’s, nothing around breast cancer, for instance. And another principle is that there's has to be already existing pathways within the NHS so that the babies can be seen and treated quickly. So, we're only including those conditions that start in childhood, and something can be done about them early on. 

Naimah: You can also listen to our podcast on our website 'Which conditions will we look for initially in the Generation study?’ to find out more about the list of 200 conditions, which we'll look for in the study and how this may change over the course of time as new evidence emerges. 

So, another common theme with the parents was that they are aware that the NHS is already under a lot of pressure, and they asked if my baby is flagged for more testing, will I really be able to get the support I need from the NHS in time?  

Mathilde: Yeah, that's a question that we've heard a lot actually, and it really makes sense considering the media coverage that's coming out daily, and that's been really in the papers for months now about how stretched the NHS is. 

We've worked really closely with the NHS to ensure that all the babies that have a condition suspected as part of the Generation Study can be seen as soon as possible. So, our team has been in touch with specialists from across the country to understand how ready they are to take in those babies, to run confirmatory tests and potentially start treating them sooner. 

So, it's been really key for us to make sure that we're not flagging up a baby for more testing and they just have to wait for months before they can get extra tests and attention. And that's so important for us to get right. In the long term, we hope that screening could actually relieve some pressure from the NHS if we can get babies to the correct doctor earlier on while their health is still good. 

Naimah: Some parents might also ask, this research sounds very new. Is my baby going to be a Guinea pig?  

Mathilde: Those two words, Guinea pig, came up again and again in almost every single session that I've had with parents, it was almost a freaky coincidence. I find that most parents use this wording to mean, will we inject anything into their baby or give them any medication that has not been tested and approved? 

And the answer to this is no. What does happen is that when a baby's born after the birth, we need to take a few drops of blood so that we can create their genome, their DNA, and normally we'll take a bit from their umbilical cords, and that is happening in most of the birth at the moment of the participants. 

But if for any reason we couldn't take that, maybe it was a complex labour, there was some emergency. The parents are asked a bit later if they would allow for a bit of blood to be collected using the heel prick methods. And that's a method that's been used in the babies in the UK within 5 days of birth for many, many years. And it looks for 9 conditions, as a current NHS test. So that's definitely safe. And usually when parents find out that that's all there is to it, they feel a lot more comfortable. A little disclaimer here because we mentioned the 5-day heel prick, while we use a similar method to get the blood, if we couldn't get blood from the umbilical cords, it's important to see that this is a different test, it's a proven test within the NHS which says many lives. So, parents who choose to take part in the Generation Study are very much encouraged to also agree to the day 5 newborn screen screening.  

With all of that being said, this is a new research study and there are some uncertainties. Most of them revolve around how quickly we can process the results, how will parents and the NHS react to receiving these results so early, but also will this be inclusive for everybody? And might we inadvertently create more inequities? We're actively listening to sites now that we have opened and we have a survey that our participants can fill out, and we're working with UCL to help evaluate the impact of the Generation Study in an unbiased way. 

Naimah: Okay. And another frequently asked question, if you have my baby's DNA, does that mean that you can clone them?  

Mathilde: Cloning comes up regularly in our interviews with parents, though sometimes I found that people can feel a little bit silly asking about it, but actually it's a quite big topic that's top of mind when we talk about DNA and genomes. 

Not least because of how much it comes up in sci-fi, it's just everywhere. So first of all, about cloning, it's important to remember that it's completely illegal, but it also has a whole host of other ethical concerns, which we don't take lightly at all here at Genomics England. So, the research that our study will support will be firmly within the bands of law and ethics and will only focus on discovering answers to questions that could help the health and wellbeing of babies, and really all of us in the future. No cloning involved. 

Naimah: Okay. And then the final question, how can I take part in the study? 

Mathilde: We've already opened in over 10 hospitals in England, which we are very excited about and we're actively working on opening more. You can visit our website, www.generationstudy.co.uk, to see an up-to-date list of hospitals which are currently taking part, and to read more about what taking part entails. Then you can contact your local research team to log your interest if you're planning on giving birth in one of our partner hospitals, and they'll be in touch to let you know about the next steps. 

Naimah: That was Mathilde Leblond answering some of the frequently asked questions from parents that we have engaged with for this study. If you've got any questions or you'd like to hear more, please contact us at [email protected], or you could find out more on the Generation Study website www.generationstudy.co.uk. 

Thank you for listening.

In this explainer episode, we’ve asked Callum Morris, Pharmaceutical Research and Development Insights Manager at Genomics England, to explain what happens in a clinical trial.

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

If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on [email protected].

You can download the transcript or read it below.

Florence: What happens in a clinical trial? I'm joined with Callum Morris, Pharmaceutical Research and Development Insights Manager for Genomics England, to find out more. So, Callum, first things first. What is a clinical trial?  

Callum: So, a clinical trial is a study that looks to people to answer a specific medical research question. 

So, this involves gathering a group of participants that are willing to participate in providing evidence on how to improve clinical care. And so, the main purpose for a clinical trial is to evaluate health related outcomes between different groups of participants. If it's an interventional clinical trial, you change clinical care for one group and not another. 

And evaluate whether the change you made improved health outcomes for that group, or if it's an observational clinical trial, you might focus on different groups but not change anything about their clinical care and collect real world data to understand how outcomes differ across the groups. 

Florence: Can you briefly explain what we mean by real world data?  

Callum: Sure. So real world data relates to data collected routinely as part of standard clinical care. So, it could be collected from your electronic health records, data from product or disease registries, or data gathered from other sources such as digital health technologies. 

And all of this can inform on particular groups from the population you're interested in. 

Florence: And are there different types of clinical trials?  

Callum: Yes. Clinical trials can take many forms depending on the medical research question you're trying to answer. They could be related to understanding the risk of disease. So, evaluating a potential risk factor that you may be concerned with. They might evaluate preventing disease. So, what different approaches can you take to people who have never had the disease, and does this prevent its occurrence? You can have a clinical trial that looks at screening for disease. For cancer, that's really important. 

Does a new screening approach mean more people with cancer can be identified earlier? And importantly, does this lead to an improvement in survival? You can have clinical trials that evaluate the different approaches to diagnosing a disease and can you diagnose a patient earlier and better? 

And then the classical clinical trial is revolving therapeutics or different treatments, and you can have treatments that are addressing the disease itself. Or you'd have treatments that are controlling the symptoms of side effects you might get from another treatment you might be taking.  

So even within a specific medical research question, you can have different clinical trials depending on how much evidence you already have regarding that question. For clinical trials involving the assessment of new treatments and therapies, these are broken down into three stages and we call these phases. 

So, you have phase one, phase 2, and phase 3. 

Florence: Can you explain a bit more about these phases?  

Callum: Sure. So, the overarching medical research question might be, what is the safety profile of this new therapy, and does it work improving on the current standard of care? So, you'll break this down depending on the phase, and with each phase you expand your clinical trial to a larger population. 

Phase ones are typically on a small group of people around, let's say 20 to 50, and are designed to check the safety of a new drug that's being entered into humans for the first time. Sometimes, especially in early phase cancer trials, you're trying to find the right dose for your patients. 

So, you might take a small group, test them on a low dose, and if there are no severe reactions to the new drug, you start incrementally increasing your dose a little bit more. And this gives you a really good idea of the safety profile of your drug as you try it for the first time in a human population. 

Next, you'll move on to a phase 2. And these are typically larger than your phase one, around 50 to 200 people. And, usually you use the dose recommended by the phase one. So instead of slowly adjusting your dose and just focusing on the drug safety profile, the phase 2 will evaluate the safety of the medicine in a large population, but also have an additional focus on health-related outcomes. 

Is the medicine causing the effect you want? Whether that's relief of symptoms or for cancer reduction in the size of your cancer. If the data is really promising from your phase two, it will move to a phase 3. And the idea is the same, increasing the size of the population. typically phase threes can be from 300 to 3000 participants. 

And the key thing here is that you will evaluate the potential benefit of your new treatment against the current standard of care. Normally, meaning the treatments that are already available in the clinic. Health regulators will need to look at all the data collected from all the trials before they approve it for the general population. 

And typically, they need a phase 3 to do this. They need a phase 3 to confirm that the benefit provided by the treatment outweighs the potential risks associated with it, across a fairly large cohort of participants. And this is to ensure the therapy is appropriate to be given to the general patient population. 

But also, a phase 3 is needed to see that if the new treatment is moving clinical care forward in the right direction and in providing improvements for patients against what is already available in the clinic. And this is the process by which we call it evidence-based changes, to make improvements to clinical care. 

Florence: So then how do people join clinical trials? 

Callum: So firstly, it's about becoming aware of the clinical trial. You might be referred to a clinical trial by your doctor who's been aware of it and where it is. Or you might be able to find a clinical trial using clinical trial databases or finding about them through patient advocacy groups. 

And they should be able to tell you which hospitals are taking part in the clinical trial. So, the next step might be your doctor can contact someone on the research team, and there is always a principal investigator per research site that is always a medical professional. 

The study team at the site have all undergone training from the people organising the trial to run through the protocols necessary to keep the trial consistent in different sites. 

Once they've been contacted, you'll undergo a screening process, and what they'll determine is your eligibility for the trial. They might assess medical history or your health status. And if you're eligible for the trial, the next step is to provide informed consent. The healthcare team should provide detailed information about the trial, its risks and benefits, the aim of the trial, and who's funding it. 

And what are the treatment options for participating and not participating in the trial? How long is the follow-up in the clinical trial? And what will happen if you leave the clinical trial? And then also what are the safety concerns for the clinical trials and the possible side effects if it's something to do with a new treatment. Once you've been informed of all these details and you agree to be part of the clinical trial, you'll sign a consent form, and that means you're officially enrolled in the clinical trial. 

Florence: And what happens once someone is enrolled in a clinical trial?  

Callum: Once you are in the trial, you'll follow the procedures outlined in the trial protocol. This can take many forms, but normally it involves more regular follow-ups and check-ins with the clinical care team. And this is to establish safety concerns and to enable lots of data collection. 

There also may be additional checks related to health outcomes during the trial, and so the study team may want to take additional samples to understand what is happening physiologically during the study. There also may be additional questionnaires for you to fill out, to capture patient reported health outcomes. 

And this is to understand the patient's quality of life whilst they're on the trial. So, depending on the protocol, you may be followed up for a set period of time, and that may get less frequent as time goes on. And of course, you may pull out of the trial at any point after which the follow up will stop. 

So, following data collection, there may be a while before you see anything, but results should be published following analysis of the data.  

Florence: And finally, why might someone want to be involved in a clinical trial?  

Callum: Clinical trials are all about providing evidence to improve clinical care. At any time we want to make a change to healthcare, we want it to be evidence-based. And so, this requires lots of people all contributing in a group effort to generate a data set large enough to determine how to change our approach to healthcare and move the field forward for improving people's lives. 

Florence: That was Callum Morris explaining what happens in a clinical trial. If you'd like to hear more explainer episodes like this, you can find them on our website www.genomicsengland.co.uk. Thank you for listening. 

In this explainer episode, we’ve asked Nicole Chai, Research and Development Bioinformatician at Genomics England, to explain what X-linked inheritance is.

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

If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on [email protected].

You can download the transcript or read it below.

Florence: How does X-linked inheritance work? I'm joined by Nicole Chai, Research and Development Bioinformatician for Genomics England, to find out more. So firstly, Nicole, can you explain a bit about the X and Y chromosomes?  

Nicole: Sure. So, the X and Y chromosomes are what we call sex chromosomes. And chromosomes are packages of DNA in our cells that are inherited from our parents, and they contain information about our physical and biological traits. 

Some examples of traits that are determined by our chromosomes include what colour our hair is and what colour our eyes are. And each of these individual traits are determined by smaller sections on the chromosome called genes. Genes can also determine what medical conditions we may inherit from our parents. 

As humans, we all typically have 23 pairs of chromosomes in each of our cells. One of these pairs consists of the sex chromosomes, and as their name suggests, sex chromosomes determine sex of an individual. And typically, females will have two X chromosomes and males will have one X and one Y chromosome. 

Florence: So then, what do we mean by the term X-linked condition? 

Nicole: So, an X-linked condition means that the condition is associated with genetic changes on the X chromosome. And what we mean when we say genetic changes are changes to the normal sequence of DNA on the gene. And this can sometimes lead to medical disorders. 

Florence: Do you have a specific example of an X-linked condition?  

Nicole: Sure. So, an example of an X-linked condition is Duchenne muscular dystrophy. 

And with this condition you get a progressive loss of muscle due to the lack of a protein known as dystrophin. Another example of an X-linked condition is red-green colour blindness. And this is where people affected with the condition can't see shades of red and green the way most people see them.  

Florence: Could you explain how X-linked conditions are inherited?  

Nicole: Sure. So, for many conditions, there are two ways they can be inherited, either dominantly or recessively. Dominant inheritance is usually when you just need one copy of the gene to be affected by the condition, whereas recessive inheritance is when you need two copies of the gene to be affected by the condition. 

However, this works slightly differently with X-linked conditions, and most X-linked conditions are inherited recessively. 

Florence: So why does inheritance work differently for X-linked conditions? 

Nicole: So the reason that inheritance works differently for X-linked conditions is down to the differences between sex chromosomes, between females and males. As females have two X chromosomes and males have X and Y, this means that for recessive excellent conditions, males only need one altered gene to have the condition. 

So, because males only have one X chromosome, if they inherit a faulty copy of a recessive gene, they don't have another healthy copy to compensate. 

On the other hand, as females have two X chromosomes, if they inherit just one faulty copy, they do have a healthy one that can compensate for that one. So as a result, what we tend to see is that males are more commonly affected by X-linked recessive conditions. 

Florence: That was Nicole Chai explaining the term X-linked inheritance. If you'd like to hear more explainer episodes like this, you can find them on our website www.genomicsengland.co.uk. Thank you for listening. 

In this explainer episode, we’ve asked Arina Puzriakova, Scientific Curator at Genomics England, to explain what a polygenic disorder is.

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

If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on [email protected].

You can download the transcript or read it below.

Florence: What is a polygenic disorder? I'm joined by Arina Puzriakova, Scientific Curator for Genomics England to find out more. So, Arina, first things first. How can our genes affect our health?  

Arina: So, genes are short sections of DNA that contain information that the cells in your body need in order to make proteins. Each gene carries the instructions for making a specific protein, and each protein performs a different task that allows the body to develop and function properly, depending on the genes that we inherit from our parents. Also determines our unique physical features such as our eye colour, hair colour, and height. 

When a gene contains a change that disrupts the gene's instructions, also known as a gene variant, in some cases, this can lead to the production of a defective protein or prevents a protein from being made altogether. A missing protein or one that is not working properly can have a knock-on effect on how the body functions and this can result in health issues or the development of a genetic disorder. 

Florence: So then how can a gene variant lead to a disorder?  

Arina: So the genetics of each disorder are unique. In some cases, a change in a single gene is enough to cause a genetic disorder, and these are known as monogenic disorders. These conditions often occur in childhood and tend to cause severe illness. individually, they are more rare affecting a smaller number of people in the population, and usually they run in families as parents pass the damaging variance onto their children. 

But these changes can also happen spontaneously without a known cause. An example of a monogenic disorder, which some may be familiar with, is cystic fibrosis. Cystic fibrosis affects one in every 2,500 babies born in the UK, meaning that there's about 11,000 people living with cystic fibrosis. 

Florence: So, we've just talked through monogenic disorders. What do we mean by polygenic disorder?  

Arina: So polygenic disorders are on the other end of the spectrum for disorders. 

They are caused by the combined effects of multiple different genes. Individually, each gene has a very small effect on causing the disease, but many variations in different genes can act together to have a great impact on individual's susceptibility to that condition. Environmental and behavioural factors such as your lifestyle and diet also often have an effect. 

Polygenic disorders are much more common, typically affecting millions of people in the population, and they're usually diagnosed in adulthood.  

Florence: Could you give me an example of a polygenic disorder?  

Arina: A common example of a polygenic disorder is type two diabetes. It affects almost 4 million people in the UK. 

So this means that we know there are many genetic variants that could have made these individuals more susceptible to diabetes, but there are also other factors such as age or being overweight that could have increased their risk. 

Florence: Are there specific challenges when it comes to diagnosing or treating polygenic disorders? 

Arina: So, if I start with monogenic disorders, these are much easier to test for because we simply need to look for the presence or the absence of a faulty gene in order to determine whether someone is a carrier of a genetic disorder. On the other hand, testing for a polygenic disorder is a lot more complex as they are influenced by the combined effects of many genes. 

Meaning there is no single genetic test or treatment that will work for all patients with the same condition. We need large and diverse groups of patients to study in order to accurately determine which genes are important and which ones are not. 

And this can be challenging to obtain. Also accurately measuring and comparing lifetime environmental factors and exposures further complicates the assessment. 

Another challenge with polygenic disorders is that even though they can cluster in families, the inheritance is not as clear cut or predictable as it is with monogenic disorders. Carrying a specific combination of genetic variants that are already known to be associated with polygenic disorder does not necessarily mean that you will definitely develop that disorder. 

However, this information can be used to calculate something known as a polygenic risk score, and this provides an estimate for the risk of developing polygenic disease at some point in life based on individual's unique genetic profile. 

Florence: And why can knowing apologetic risk score be helpful? 

Arina: So, by being informed about the probability of developing a particular polygenic disease, an individual can make behaviour or lifestyles changes that could help reduce their risk. To go back to the previous example, somebody who is more likely to develop type two diabetes based on their genetic makeup can do things like maintain a healthy weight. And eat a healthy diet to help reduce their risk of developing type two diabetes in the future. 

Florence: That was Arina Puzriakova explaining what we mean by polygenic disorder. If you'd like to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk. Thank you for listening. 

The Generation Study is a research initiative aiming to explore the use of whole genome sequencing in newborns, to screen for more than 200 rare genetic conditions. This study will recruit 100,000 babies across England, and you can learn more about the Generation Study via the study's official website.

Design research has played a vital role in shaping the Generation Study. Parents, NHS staff, and the public have been involved from the start, providing input through public dialogues and usability testing to guide the development of the study.

In this episode, our guests discuss the use of design research in the Generation Study, and the importance of designing a robust and inclusive consent process, focusing on building trust and engaging diverse communities. They also discuss how the design of study materials such as posters, videos, and written content was shaped by community feedback.

Our host, Öznur Özkurt, Director of design and research at Genomics England is joined by Mathilde Leblond, Senior Design Researcher at Genomics England, Rebecca Middleton, a rare condition patient, and Chair of the recruitment working group of the Generation Study and Sandra Igwe, CEO/founder of The Motherhood Group.

"It’s not enough to just ask people afterwards. It’s also not enough to engage just at the beginning and then stop listening once we’re live, once it gets hairy and a bit difficult. So, we are very excited to find out all the things that we hadn’t considered before we launched, and just continue to learn."

You can hear more information about Generation Study in our previous podcast episodes too:

• Genomics 101 with David Bick - What is the Generation Study?

You can download the transcript or read it below.

Öznur: Welcome to Behind the Genes. 

Sandra: Every community’s different and every patient is different as well, and so that may require different focuses or different formats, or different messages for different groups. And so we like to have people with lived experience from the community representing that, and also driving the uptake of consent as well. But failing to engage diverse voices can lead to perpetuating inequalities in access and uptake, so it’s really important to have representation because the lack of it in research can overlook communities’ specific concerns and needs. 

Öznur: My name’s Öznur Özkurt and I’m the director of design and research at Genomics England. On today’s episode, I’m joined by Mathilde Leblonde, senior design researcher at Genomics England, Rebecca Middleton, and Sandra Igwe, CEO and founder of the Motherhood Group. Today we’ll be discussing how design research was used in the Generation Study by involving participant and users’ voices to address ethical considerations, implementation and consent. If you enjoy today’s episode, we’d love your support. Please like, share and rate us on wherever you listen to your podcasts. 

So, before we dive into our questions, would our guests like to briefly introduce yourselves to our listeners? Sandra, let’s start with you. 

Sandra: Hi everyone, I’m Sandra Igwe and I’m the founder and chief exec at the Motherhood Group. The Motherhood Group is a social enterprise that supports black mothers, birthing people in their pregnancy and beyond. 

Öznur: Great to have you on the podcast, Sandra. Rebecca? 

Rebecca: Hi everyone, I’m Rebecca, I’m a rare condition patient, and I also have the pleasure of chairing the recruitment working group of the Generation Study. 

Öznur: Fantastic, thank you, Rebecca. And over to you, Mathilde. 

Mathilde: Hi, I’m Mathilde. I’m leading design research on the Generation Study, and I have had the pleasure of working with Sandra and Rebecca and many others, trying to shape the processes and materials of recruitment and consent in the Generation Study. 

Öznur: Fantastic, thank you. Mathilde, let’s start with our first question. What is the Generation Study? 

Mathilde: Sure. So, whole genome sequencing is a technology that’s improving. We’re finding new ways of using that, and there’s interest globally to explore the use of this technology to screen for rare genetic conditions in babies, so that we can treat them earlier on, so they’re not having two different departments trying to figure out what’s wrong with them. And because we can look for hundreds of conditions with whole genome sequencing, it’s really much more efficient, and we’re able to look at these rare conditions, so it’s really exciting. There’s still a lot of questions about implementing this operationally within the NHS, and so the Generation Study is aiming to explore this. We’re going to be aiming to recruit 100,000 babies across England to take part in this, and they will be staying on the Generation Study for 16 years, or until they withdraw, so that we can see how their health develops, and really understand how genes affect their health. 

Öznur: Thanks Mathilde. And if you’d like to learn more about the Generation Study, you can listen to our previous Genomics 101 podcast called What is the Generation Study, and Which Conditions Will We Look for Initially in the Generation Study. 

Mathilde, can you briefly outline for us what we mean by design research? 

Mathilde: So, design research is a design and research methodology, which involves users from scoping through iteration. So, even back when we didn’t know this would be called the Generation Study and we weren’t even sure of the boundaries of that, we were involving parents, NHS staff and other users of the service to try and understand what it might be. And later down the line it went all the way through to iterations once we started having materials and a better idea of what it could be like (inaudible 0:04:18) with users outside of the company to understand what their needs are, what would work well for them, and how we can shape the whole service to do things better. 

Öznur: And how have we implemented design research in the Generation Study? 

Mathilde: Yep, so we’ve also done a lot of engagement, which was bringing public views in the form of public dialogues, so understanding which conditions should be looked for, what principles should be guiding that work, but also we’ve been involving users in regular rounds of codesign and usability testing to understand what works and what doesn’t work. It’s been around 105 people now that have taken part, and it’s only going to be growing. Involving users has been shown to improve the implementation of interventions in the healthcare context, so we really hope that this will help the Generation Study when it launches. And regular rounds of codesign have had to be balanced with ethics, operations, feasibility, but I’m proud to say that user perspectives have been central to the decisions of the programme throughout.  

Öznur: That’s fantastic to hear. I’m going to come to Rebecca and ask, why is it important for us to be guided by the patients and the participants? 

Rebecca: It’s absolutely central, and the public dialogue that really underpinned this, which started in 2020, the messages from that have really come through to the whole codesign process of the project. The public consultation really told us that people were genuinely keen about the project, but wanted to ensure that they were part of the process, and that coproduction really began from day one. This is a new world leading project. This has not been done before, so we needed a whole new approach to how we produced and how we designed this with patients and with parents, and that’s exactly what we’ve done. And why we have done it is because we know ultimately it leads to trust within the project, within the research study, which is essential, as I say, ‘cos this is a world first. But it also leads to better consent, a better pathway through the study, a better results pathway as well, and all the way through, ensuring that expectations are managed, that there is transparency, and people are fully informed and can make the right decision for themselves and for their baby.

Öznur: Thank you. And would you like to add something, Sandra? 

Sandra: Yeah, so I know from my community that we represent black mothers and black ethnic minority patients and participants, and we have very unique lived experiences that many research may not be privy to or just do not understand. And so engaging with patients from the community ensures that research is grounded in real authentic community needs and priorities. And also involving women like myself and those from my community, it can really help to identify and overcome barriers to inclusion or getting mums involved. I know I always hear, you know, “Sandra, black mothers are so hard to reach, they don’t really get involved in research.” Well, if you include those from the community to lead in the research or support in engagement, you will have a lot more uptake, and it leads to more accessible inclusive research, which of course everyone really, really desires to have more of.  

And then also participants from the community can flag issues and suggest solutions that researchers may miss, because it’s not knowledge, it’s experience. It’s, you know, having someone go through the experiences without necessarily studying it, but again lived experience to me, it’s more crucial than any other experience that you could possibly have. 

Öznur: 100 percent, lived experience is really, really crucial for us to make the services that we’re making really speak to the actual context of our users. Thank you for that. And Rebecca, how has this process been different to the 100,000 Genomes Project? What was your experience?

Rebecca: I was consented onto the 100,000 Genomes Project back in 2015, and I can remember that experience very vividly, on a cold, wet December afternoon, going off to meet my genetic counsellor, and receiving the consent form for the 100,000 Genomes Project, which was very much like War & Peace. Scratching my head at the time, going, “Gosh, I’m going to have to (inaudible 0:08:54) to go through this.” And then going home that evening and sitting on the sofa, and, you know, considering myself an educated woman, just realising I had so many questions. I really didn’t understand it, and I needed somebody to help me unpack this, and translate it. And I’m pleased to say that our consent process and our recruitment process is very different to this, which is a fantastic thing.

And what’s really key about the lessons that we have learnt from the 100,000 Genomes Project is that, to really build trust in a research programme and a new research programme, you need to manage expectations, and that’s wrapped up in building trust around the programme as well. And with the 100,000 Genomes Programme, there have been challenges and issues around that expectation management, and some expectations weren’t managed. And even now nearly ten years on, we are still feeling the effects of that, and patients and families are still feeling hurt because of that. So, we have learnt from that and therefore we have designed a process with patients and with parents. We know that no two experiences are the same, that we have to ensure that we remain flexible, and we have to ensure that we are addressing any misconceptions, any misunderstandings.

Perception and reality have to be treated the same. We have to understand how people are understanding genomics, because outside of pockets, genomics is not a standard NHS piece of healthcare. So, people come to this study with different assumptions, and we have to learn to go beyond them. We have to understand what their health literacy needs are, and how we can help manage that, how we can help translate, so that nobody is stuck at home on a cold, wet December evening, scratching their head, going, “Well, I don’t know what this actually means.” We are ensuring that the NHS professionals and everybody involved in the pathway is fully aware of how to explain the project, explain the risks, explain the benefits, and be fully transparent. And we know what the risks and the benefits are that need to be addressed because we’ve asked parents and patients as well.

So, we know the challenges and we’re trying to address them head on, and that’s essential. It’s essential in building trust, and that’s one of the key learnings from the 100,000 Genomes Project. And it has been brilliant to be involved in this project and really kind of learn from that past experience, but move forward in such a unique and fresh way that really will have benefit to those new parents.

Öznur: Thank you, Rebecca.

And we have been talking about the consent process in the context of newborns, and we know that, while consent given for newborn screening is really high in the UK, parents often leave this conversation relatively uninformed. Sandra, can you tell us a little bit about what you think the risks of not designing this consent moment appropriately might be?

Sandra: I guess not designing appropriately can break down trust. So, I think engaging in a variety of parents in this research and design is crucial for trust. And that’s a topic that’s come up many times in our community is that they believe that there is a lack of trust between research practitioners and this wider system as a whole, and the community of marginalised patients, parents, mothers. So, I think it’s really important that communities have this. But also researchers must make the effort to meet parents where they are at, not just physically but also conceptually, as well as emotionally. So, hosting conversations in familiar, comfortable community spaces is essential. We had our session in our hub, our community hub, and mothers were really familiar with the space and with each other as well. And so partnering with local grassroots organisations and leaders to create inroads is so beneficial, and I can hand on say that when you connect with the community, you’ve already done the first step in building trust.

And consent conversations should be guided by what matters most to each parent within each community, ‘cos every community’s different and every patient is different as well, and so that may require different focuses or different formats, or different messengers for different groups. And so we like to have people with lived experience from the community representing that, and also driving the uptake of consent as well. But failing to engage diverse voices can lead to perpetuating inequalities in access and uptake, so it’s really important to have representation because the lack of it in research can overlook communities’ specific concerns and needs.

Öznur: Absolutely, and that inclusion is really important for the study. Is there anything you’d like to add, Mathilde?

Mathilde: Yes. When we talk about consent, oftentimes we think about that one moment, the moment of conversation with a clinician, and signing on the dotted line, and I think what we have done here in the Generation Study is to consider recruitment from the very first time that they hear about the Generation Study all the way down to that moment. And it’s been really important because, yes, the moment of consent - you know, during pregnancy, you’ve got a lot of information coming in, a lot of different priorities, so you may be a little bit all over the place and not understand specific things, or not have the time to really spend thinking and understanding jargon, etc. And that presents a big risk because, when you may receive results, there may be confusion. There may be a loss of trust if there’s media coverage that talks about the Generation Study in a way different from what you had understood it. So, these are some of the risks that we’re trying to avoid. 

But the big risk is also, as Sandra has said, the risk of not engaging a wide variety of parents, not just in the moment of consent but the whole process. So, if we’re thinking about where we’re using the word genomic and how are we using that, this is a word that’s actually really scary for a lot of people. And we might be very proud of the cutting edge technology that we’re using, but actually it can sound very science-y and almost sci-fi to people. So to us, the moment of consent is really from the first time that you hear about the Generation Study, you start creating a mental model about what that means, all the way down to the consent moment, when the samples are taken, the results and beyond. It’s really been looking at this whole journey holistically.

Öznur: And that language point is a really interesting one. I know that the study is obviously being communicated to the public through posters, leaflets, websites, which speak to how the study works, you know, the conditions we test for, and the benefits and risks of joining. There’s a lot of language. There’s written words in there, there’s audiovisual content, videos, images. How did we inform what type of content is needed to communicate the depth of the study?

Mathilde: I think the example of the introduction video is a really good one, and I want to discuss this a bit with Sandra, because actually it was quite a crucial turning point. We tested the video several times in user research before and after the Motherhood Group workshop, but the thoughts that her community gave us really helped change the tone of this video from something very professional to a conversation between parents raising questions. I wonder, Sandra, if you remember what your community’s feedback had been, and if you can talk a little bit about that.

Sandra: Yes. So, the mothers from our community at the Motherhood Group definitely gave lots and lots of feedback that the initial posters didn’t really resonate with mothers from our community. They said that the visuals and the language felt a little bit generic and also too clinical, and it didn’t speak directly to our community. They also expressed that seeing more black parents and more black families represented signals for us too as well – so, seeing people like look like us in the posters and the media would have allowed a lot more uptake. So, narratives and videos featuring real people that looked like members of our community, they expressed that would go a lot further. And also it made them feel a lot more relevant, and again it goes back to the notion of having more trust and feeling less abstract, but more like an authentic way of engaging or directly communicating with our community.

They also appreciated the effort to be more upfront, but the risk and also the downside, not just selling only the positives. You know, members from our community were saying they wanted to know the real deal. And also our community have been misled in the past. You have to understand that. The history kind of shows that there has been a breakdown in trust, and so transparency, they shared, was really, really key to rebuilding that trust, as well as materials that are culturally tailored and designed for different formats for our community.

Mathilde: It’s really exciting how much this feedback has pushed all of us in the team and the designers – pushed us to think about how to talk about the Generation Study, what narratives to use, what tone of voice, but also you’ll see on the posters there’s space there to have photos of several different family types and people of different backgrounds. It’s not just one photo. And there’s also some very small tweaks, it seems like, but it actually has a very big impact, about what it is that you’re trying to say and what people understand in a split second when they’re seeing that.

Öznur: Absolutely, and that open dialogue is definitely key to keeping on bringing those perspectives in, and keeping updating and moving the language of the study as well. Obviously, the study will keep being shaped. I’m curious about how will design research continue to shape the Generation Study going forward.

Mathilde: Yep, so we will have an iterative process, where we’re still listening to the sides as they’re launching to hear what are the questions that are being raised, what are some of the challenges that they’re facing. At the same time, we have a survey that parents will be able to fill in, and we have an evaluation partner, UCL, who is doing an independent review of how well all of this is landing, and evaluating the work that we’ve been doing to see is it really hitting all of these points, and what we may need to be iterating or changing as we learn.

Rebecca: I should also point out that the recruitment working group is very much in the background, but we are still very much alive, and we will come back to look at those first pieces of feedback and to look at what the experiences have been, and how we can learn and how we can help kind of shape what comes next. Because it’s critically important that we have this always learning philosophy. It’s critically important that now, you know, the rocket has launched, how will it land, and we don’t know until we’ve actually had that feedback. So, we can plan and absolutely plan to the nth degree, but actually how it exists out there in the real world, we won’t know until the project goes live and that feedback comes through. And that’s what we’re also really excited about is to actually learn those first lessons and see how we can support going forward, and see what needs a tweak here, a change there. And again, it’s that dialogue that started with the public dialogue back in 2020, and here we are in 2024 and that dialogue will still continue, and we are still listening and we are still learning.

Öznur: Thanks Rebecca. I’d like us to reflect on the importance of continuous learning. What’s the importance of continuous learning in this project? I’ll start with Sandra.

Sandra: Continuous learning to me and my community really means listening to the voices that are often seldom heard. It means trusting and placing trust in the community to be a part of or lead or be involved in research, changes that affect our community. It also means actively and proactively working to rebuild that trust, because there’s been a lack of trust from the community, and that means transparency. It also means honesty, and it also means continuous involvement as well. There’s no point in involving us at the end of a study for our feedback, but at the very start to show that you are trying to be authentic. 

Rebecca: Ultimately, genomics is the science of people. Genomics is people, so we have to keep talking to the very people that we are looking to try and support, help, care for, and ultimately impact them and their families as well. So, I completely agree with Sandra, continuous learning, it’s a continuous dialogue, and understanding how our opinions differ, how our opinions may shape and grow as the general conversation about genomics continues as well in the public discourse. So, we have to understand and we have to stay sort of on our feet, that this is a dynamic conversation, therefore we need to change and we need to remain flexible as well. And if we keep our ears open and if we keep our minds open, then we will continue to build that trust, and we will continue to ensure that we have a robust study that will ultimately fulfil its research aims.

Öznur: Thank you. And Mathilde? 

Mathilde: I think there’s only so much that we could really cover in theory before we launched, and now, you know, it’s going to go out into the world, and there’s many things that we couldn’t have predicted that will happen. We have that humility to understand that. And what’s super important going forward is that we have a team there to keep kind of staying on our toes, listening to what’s happening, to make sure that we respond to that, so that, as Sandra said, it’s not enough to just ask people afterwards. It’s also not enough to engage just at the beginning and then stop listening once we’re live, once it gets hairy and a bit difficult. So, we are very excited to find out all the things that we hadn’t considered before we launched, and just continue to learn.

Oznur: We will wrap up there. Thank you to our guests, Rebecca Middleton, Sandra Igwe and Mathilde Leblonde for joining me today as we discussed the use of design research in the Generation Study. If you’d like to hear more episodes like this, please subscribe to Behind the Genes on your favourite podcast app. I’ve been your host, Öznur Özkurt. This podcast was edited by Bill Griffin at Ventoux Digital, and produced by Naimah Callachand.

In this explainer episode, we’ve asked Amanda Pichini, Clinical Director at Genomics England and Genetic Counsellor, to explain which healthcare professionals you may come into contact with in your genomic healthcare journey.

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

If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on [email protected].

You can download the transcript or read it below.

Florence: Which healthcare professionals are involved in my genomic healthcare journey? I'm joined with Amanda Pichini, Clinical Director for Genomics England, and genetic counsellor to find out more. So firstly, when someone has a genetic or genomic test, what kind of healthcare professionals might they come into contact with? 

Amanda: Well, everyone has a different journey, and it can depend on the type of test you have and the reason for having it. Some tests might only look for a single gene. Some might look at many genes, and some look for a very specific gene change that's already known to be in someone's family. Some genomic tests are there to find the cause of a person's diagnosis, understand more about their cancer, or maybe to predict a future health problem that they may have or that's in their family. 

So usually people start with their GP, who they go to with a question about their health or their child's health, and this could lead to them being referred to a clinical genetic service or perhaps another specialist team.  

Florence: So, then what is the purpose of a clinical genetics team? 

Amanda: Well, a clinical genetics team, in brief, aims to provide people that have a genetic condition or are at risk of one with health information, including information about prevention, counselling support, and genomic testing, and they focus on the whole family. 

Adults and children can both be seen in a genetic service. Clinical genetics teams tend to focus on rare conditions and rare predispositions to certain types of cancers, so really anything that might have a strong genetic basis and could impact someone at any stage of their life. A clinical genetics team is made up of a range of roles, and that could include clinical genetics, doctors, genetic counsellors, clinical scientists, and administrative staff. 

Florence: Could you tell me a little bit more about each of those roles?  

Amanda: Sure. I am a genetic counsellor, so I'll start with that. Genetic counsellors are specially trained healthcare professionals that help patients and families understand information about their genomic health, as well as provide guidance and emotional support. 

So, this could be about understanding their family history, making informed choices about having a genetic or genomic test, or helping them to come to terms with a result or a new diagnosis and the impact that could have on them or their family. Clinical geneticists are medically trained doctors that specialise in genetic conditions. 

They understand the underlying ways that genetics can affect health, and they use that to help make diagnoses for patients. How about genomic scientists? These are often not seen directly by patients, but they're vital to someone's genomic healthcare journey. So clinical genomic scientists and genetic technologists work in labs, and they're involved in processing patient samples, working with those other healthcare professionals to select the most appropriate genomic tests to perform and interpreting those results based on the variance or genetic changes that are seen in patients, which are usually summarised in a lab report. 

There's lots of other healthcare professionals that can also, um, be in a clinical genetics team. That could include administrative staff, family history coordinators, genomic practitioners or genomic associates. They might help arrange appointments, gather medical and family history details after a referral to help the clinical team know what might be done next. 

Some genetic services also have psychologists, nurses, or other allied health professionals embedded in their team or in specialty clinics that they work with, and it's really important that everyone is working together as a multidisciplinary team to help those patients and families in their healthcare journey. 

Florence: So, we know there are lots of different healthcare professionals within the clinical genetics team. Are there any other professionals involved in genomic healthcare as well?  

Amanda: Absolutely. As genomics becomes part of routine healthcare, that means there's lots of other healthcare professionals involved in arranging genomic tests and giving back results, or at least having initial discussions about genomic tests before referring on to another specialist. 

So, some examples might be midwives, arranging screening tests for women in pregnancy, a number of those screening tests have a genetic or genomic basis. They might also refer families with a history of a genetic condition whilst they're pregnant for more specialist genetic testing. Many paediatricians are ordering genomic tests for children that might be suspected to have a syndrome or an underlying cause for their health or developmental issues. 

And many nurse specialists like those who work with people with cardiac conditions or neurological conditions. Might be involved in arranging or discussing genetic testing. Final example in the cancer world is oncologists who might often arrange genetic tests that will help give information about someone's cancer. 

The last thing to call out isn't necessarily healthcare professionals, but patient charity organisations are super crucial to someone's genetic healthcare journey. It's really important for families when they've had a new diagnosis or when they're seeking information, and there are some charities that do have healthcare professionals that work for them, like a nurse or genetic counsellor or psychologist that may help to run a helpline, for example. 

Florence: That was Amanda Pichini explaining which healthcare professionals are involved in a genomic healthcare journey. If you'd like to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk. Thank you for listening. 

Digital consent models, language barriers, and cultural differences are just a few factors that can exclude people from participating in genomic research. In this episode, our guests discuss these issues, and explore alternative methods such as in-person discussions and the use of trusted community figures to engage with their communities to increase awareness of genomic research. They also highlight the importance of communicating consent in ways that respect cultural dynamics, such as family involvement in decision-making.

Our host, Naimah Callachand is joined by Maili Raven-Adams, researcher in bioethics and policy at Nuffield Council on Bioethics, Niharika Batra, Community Projects Manager at Southall Community Alliance and Trupti Patel, Policy Manager at Genomics England.

"I think it is about finding language to involve people, and figure out how the benefits of them donating data can relate to them and their community"

You can download the transcript or read it below.

Niharika: People are usually comfortable giving their data when they feel that there is transparency from the data collector, they’re being completely transparent, they come with you with clear benefits, how it’s going to benefit the community.  And you are equally sort of agent of your own data and you feel involved in the research and you feel that you have power to give out your data and have control over the journey of that research.

Naimah: My name is Naimah Callachand, and I’m the Head of Product Engagement and Growth at Genomics England. On today’s episode, I’m joined by Maili Raven-Adams, researcher in bioethics and policy at Nuffield Council on Bioethics, Niharika Batra, Community Projects Manager for Southall Community Alliance, and Trupti Patel, Policy Manager at Genomics England.  Today, we’re going to be discussing some of the ethical, legal and social implications of genomics research for diverse communities, and how we might overcome them to address the challenge of diverse communities health needs.  If you enjoy today’s episode, we’d love your support, please like, share and rate us on wherever you listen to your podcasts.  First of all, I’m going to ask each of our guests to briefly introduce themselves.

Maili: I’m Maili Raven-Adams, I lead on work at the Nuffield Council on Bioethics to do with genomics.  This has predominantly been looking at how to develop a best practice approach for genomics, and looking at the ethical implications of AI and genomics when they’re used together in healthcare.  Before here, I worked at the Global Alliance for Genomics and Health, where I developed policies related to diversity in datasets and genomic discrimination, so I have a particular interest in this area.

Naimah: Niharika, can we come to you?

Niharika: Hello, everyone, I’m Niharika Batra, I’m the Community Projects Manager at Southall Community Alliance.  We are a charity based in Southall.  Prior to joining the charity, I was working as a Youth Community Engagement Assistant in United Nations Development Programme in India, and I have a background in gender and development.  I also bring with me lived experience of being a South Asian immigrant woman, and I’m really passionate about working with the immigrant communities in the UK.

Naimah: It’s lovely to have you.  And Trupti, can we come to you?

Trupti: Hi, I’m Trupti Patel, I’m a Policy Manager at Genomics England.  I work primarily within the diverse data initiative and I lead the equity in health research workstream.  My background is in responsible research and innovation, as well as co-production, and more ethical ways in which members of the public can shape the direction of scientific advancements.

Naimah: So, first of all, Trupti, can we talk about the challenges around equity in data, and what this means for diverse groups in the context of genomics?

Trupti: Yes, as I mentioned, I lead the equity in health research workstream.  Now we talk very specifically about equity in health data.  As Genomics England, we are a biobank, and we hold health data on individuals who have consented to be a part of genomic research. When we talk about equity, primarily we’re talking about those of non-European ancestry, and there are very specific reasons as to why that is.  So firstly, there’s a wider issue about representativeness within health datasets more widely.  We know that across all health data sets that are located within Global North countries, the data held within them tends to not be representative of their populations. And what I mean by that is that they tend to overrepresent those of European ancestry, and underrepresent anyone who is not of European ancestry.  The consequences of this is that healthcare innovation might stand to leave these population groups behind.

One of the other reasons that we talk about equity specifically, as opposed to things like equality, is that we’re also aware that if we look at research on a global level, the majority of research funding is given out through grant bodies located in Global North countries.  So we already know that research portfolios can actually be quite skewed towards population groups who live in those countries themselves.  We know that there’s a lack of financial investment as well within developing economies.  So it’s natural to assume that health innovation projects which address the needs of these communities are more likely to be conducted by researchers who are based in developing economies.  However, their access to funding is very limited, and on top of that they tend to have much smaller life sciences sectors, so their access for private funding, as well as opportunities to collaborate with industry can actually be quite limited in itself as well.

Another reason that we care about equity is that we actually know that there are some sub-populations that are very diverse within themselves.  So a good example is the genetic diversity of Africa as a whole is much larger than those who live outside of Africa itself.  And for that reason there tends to be a focus on actually oversampling from people who are of these ancestries.  And another example being South East Asians as well.  The final challenge when it comes to equity is that we also know that there has to be a need for medical innovation for these population groups, and a desire for people to actually buy this type of innovation.  So there’s a need for demand for these therapies and medications.  Now if we already know that developing economies might be less likely to be able to afford these medications, then the demand will always be lower for these population groups.  And therefore the demand for innovation might also be lower population groups.  But as a country, because we would want to make sure that we’re able to provide medication to everyone equally, we need to take an equitable approach.

So one thing about the lack of diversity within datasets actually means that we can’t always accurately predict whether or not someone does or doesn’t have a condition.  So we’re still at the stage where accuracy is not as good for these population groups as it is for others, and it leads to things that we call false positives and false negatives.  So where we think that someone does or doesn’t have a condition, and in fact, they might or they might now.  The incidence rates of that happening for anyone of non-European ancestry are higher.  That’s one of the tensions that we’re playing with at the moment, especially when it comes to providing genomic healthcare via a healthcare service.  Understanding people’s cultural background and nuances I think is really important.  For example, a lot of those cultural practices can actually play into whether or not someone decides to receive or not receive a form of healthcare.  And it’s also important to understand things like timing, so the decision around whether or not someone decides whether or not they’re going to take a preventative medication might be based upon cultural timings around things like giving birth or something.

Naimah: How can we ensure equitable access to genomic medicine for all of these communities?

Maili: So I think we need to understand that there are several understandable reasons that people might not have been involved in genomic research to date.  Efforts have been made to engage with different communities, but this has sort of been piecemeal and we need to see how that engagement can feed into research practices. So that people feel as if their information that they’ve given has been taken on board, and that those research practices have been co-developed, and they feel more willing to engage so that that representation can increase.  There’s also been examples where research has been actively untrustworthy in the past.  You know, there’s well known stories of Henrietta Lacks, whose cancer cells were taken without her consent, and then used to develop research.  And there’s different examples across the globe that kind of mirror that sort of exploitation.  So we kind of need to take note of these, and understand why people aren’t there, and then allow that to inform engagement practices.  So that research practice can change over time and be more inclusive and encourage people to get involved and give good reason for them to get involved in that.

Niharika: Also, to add on to what Trupti and Maili mentioned.  First of all, why this data gap exists, why is there inequity in genomic data?  It’s because historically South Asian communities or the marginalised communities have been used to extract a lot of data, be it social research or medicine research.  So when a researcher approached them or a data collector approaches them, they feel that they’re just going to collect the data and there will be no feedback process, or it might not benefit the community.  The communities do not understand what the clear benefits of these researches are.  And in terms of genomics, when we talk about medicine research, historically these communities have been exploited.  There has been information asymmetry, and we have observed a case in 1960s where in Coventry Punjabi women, or South Asian women, were given radioactive rotis, and they weren’t even aware what they were consuming.  And it was in the name of research.  So there’s always this hesitancy when it comes to medicine research.

One way to tackle the problem of the data gap in genomic research is by co-production . So when you're approaching the communities, it sort of helps who is collecting the data, there is no skewed power dynamic involved.  People are usually comfortable giving their data when they feel that there is transparency from the data collector, they are being completely transparent, they come with you with clear benefits, how it’s going to benefit the community.  And you are equally sort of agent of your own data, and you feel involved in the research, and you feel that you have power to give out your data and have control over the journey of that research.

So it is also important how you frame the message when you're collecting the data.  In our communities, the idea of sevā or Kismet is very embedded in the communities, which mean either giving out your services or your time for the benefit of the communities.  So it’s not just donation, but it’s just spending more time or just working with the communities for a common or a collective benefit.  So when the message is framed in such a manner that you are doing a sevā or you are helping your communities bridge the health inequalities and there might be a collective benefit for the communities, people are more motivated to give their data.  But when the word donating data is used, then it puts a sort of emotional burden on the participant.  So it all depends on the messaging, how you frame your messages when you're collecting the data, and it’s important to be cognisant of the cultural sort of ideas.  And this is something that can be used with South Asian communities, sevā and giving back to the communities.

Maili: I was just going to say, I completely agree with that, like 100%, it’s really important as well that the global majority don’t feel pressurised into giving that data because of the language that’s being used.  You know, the global majority are not represented in these datasets, so it could be that the language used might put pressure on people to donate that data to fill that gap, but that’s not the right language.  I think it is about finding language to involve people, and figure out how the benefits of them donating data can relate to them and their community, so it just wanted to say that.  And also, it’s important when we’re using language like genetic ancestry that those aren’t conflated with things like race or ethnicity, which are social uses of that language.  So I think this is just another area where it is really important to think about language and work with communities, to figure out what the right language to use it, and understand the benefits of using certain types of language.

Naimah: And it just kind of highlights how many different nuances there is, and areas that need to be considered.

Maili: Yes, I was just going to say, within that, we need to think about barriers to participation as well that might affect certain communities.  You know, there might be some language barriers, to making sure that we’ve got translators, or there’s investment in making sure that the resources are there to make the engagement and also the research accessible to people.  There’s things like people have lives, they have childcare, they have jobs, so making sure that they can donate data if they want to, at times that work for them and environments that work for them.  And things like transport costs and that sort of thing might be covered by a research organisation, so that people are empowered to get involved, and there’s not too many barriers to become involved if they want to be.  I think that’s really important to address as well.

Naimah: Trupti, did you have something to add?

Trupti: Yes, I was just going to say, I think it was really interesting that Niharika actually framed the benefit around community benefit.  Because within the policy sphere, and actually even within wider conversations on data and health, people use frame benefit in terms of patient benefit specifically.  And what we find is that when we engage with diverse communities, most of their concerns around harms are actually not harms necessarily to themselves specifically, but harms around their whole community.  And I do wonder whether there needs to be a slight reframing in how we talk about benefit when it comes to genomics in particular.  Because most people when they donate their data they know that it has consequences for those who are related to them.

Naimah: So I wanted to talk about research governance as well.  And in the context of history of medical racism, with medical innovation now heading towards personalised healthcare, what are they key considerations we should have when it comes to rules around access to data?

Trupti: So, I mean, one of the rules that we have within our biobank, when it comes to access to data, is that we don’t want it to lead to any discrimination, and we won't allow access for things, for research projects, that do lead to discrimination.  However, we already know that there are lots of unintended consequences when it comes to research in general.  And when it comes to medical research in particular, and thinking about genomics in particular, lots of communities are aware that because in the past there has been a lot of research outputs have been used in ways that actually don’t benefit these communities, and actually have negative consequences for these community groups, it means that the barrier to encourage people to take part is actually quite high.  When it comes to genomics in particular, obviously there’s been a history of eugenics, and at the moment, that’s quite a big area that lots of universities, especially in the UK, are going through eugenics inquiries.  It has effects upon people’s perceptions of genomics as an area, and whether or not people can be confident that those types of research won't be repeated, and the types of research that will happen will actually benefit them.

I mean, there’s a good example that one of the community members gave, not directly to do with genomics, but actually they knew that if you're first name is Mohammed, your car insurance is actually much higher, your premiums are much higher.  And so they were concerned that if you were grouping people within genomic ancestries, or genetic ancestries, what consequences that has for them can be quite nuanced in the first instance.  But in the long-term it would actually mean that people might be grouped within these ancestries and policies and things that are created as a consequence were quite concerning for them.

Naimah: And Maili, I wonder if you could tell me how people might feel more comfortable in the ways in which their data is being used?

Maili: I guess if there’s transparent governance mechanisms in place and they can understand how their data is being protected, you know, that goes right through data access committees.  There’s one at Genomics England that as Trupti said reviews data.  So if they can understand what sorts of considerations that committee are thinking about in respect to genetic discrimination, and they can understand that certain considerations have been taken into account when their data is being used, that’s one thing.  Another could be through consent processes.  So there’s different sorts of consent models that could be explored with communities to figure out which one they’d be more comfortable with.  So broad consent I think is the one that’s used at Genomics England at the moment.  So that means that people give their consent once, and then that data can kind of be used for a broad range of purposes.  But it’s not always clear to people what those purposes are, or where that might be used over time.

So there’s different sorts of mechanisms that could be explored, like dynamic consent, where people are updated over time about what their data is being used for, and they can either opt out or opt in to those research practices.  Or forms like things like granular consent, where when people give their consent there’s different options of people that they’d be happy for their data to be shared with.  So we know that people are less trusting of private companies, for example, so people might be able to say, “Yes, my data can be shared with nonprofit organisations or research organisations affiliated with universities or the government, but I don’t want my data to be shared with private companies.”  And that might make people feel more comfortable in donating their data, because they might feel like they have some more control over where that is ending up.  And I think transparency there is really important, so people can understand when they give their data or they donate their data, they can understand what benefit might be coming from that.  And that might encourage people to get involved as well.

Trupti: I was just going to add to that comment about dynamic consent.  So actually an interesting thing that Niharika mentioned earlier was this feeling that the people that we engage with actually really wanted a sense of control over their own data still.  Obviously when you give broad consent, your giving your consent, as Maili said, to a wide range of research that will happen or can happen in the future.  But interestingly, dynamic consent, I think culturally it is really valuable for some population groups, partly because it fits in very nicely with the idea that your biological data is actually a part of who you are. And that cultural philosophy can still exist within a lot of these communities that we’re engaging with and a lot of these communities that we’re trying to encourage to actually provide us with data.  Do you ever think that there could be like a medium position, where it was actually dynamic withdrawal?

Maili: Yes, I guess that is something that could be explored, and I think that’s one of the models that sometimes is talked about in academia or in these sorts of forums.  I think if people were dynamically kind of withdrawing, it might be interesting to understand why they’re withdrawing and their reasons for that, so that research practice can change and take account of why people maybe no longer want to get involved in a certain type of research.  And I know that’s something that you’ve spoken about in your community engagement groups.

Naimah: Niharika, do you have something you want to add?

Niharika: Yes, so when we were engaging with our communities, we primarily engaged with Hindi speaking people from Indian origin, Punjabi speaking people from Indian origin, and Urdu speaking people from Indian origin, and we spoke to them about genomic research.  We also spoke to them about the branches of genomic research and how their data could be used.  So while their data could be used for innovation in pharmacogenomics, which seemed to be more palatable for the people as this is an extension for treatments they’ve already been using.  For example, treatment for a chronic condition like hypertension or diabetes.  Whereas they were quite reluctant when it came to their data being used for gene editing.  So in Hindu religion, humans are considered the creation of Brahma, who is one of our main Gods.  And similarly in Islam, humans are called (Islamic term), which means God’s greatest creation.  So when it comes to gene editing, some people believe that it means you are playing God, it means that you're tampering with the DNA, you're tampering with God’s creation.  So they were really reluctant in providing their data for an innovation that entails gene editing or genetic screening or gene therapy.

And when it comes to consent, I know Genomics England takes a broad consent, and there’s scope of dynamic consent.  Where people are constantly engaged on where their data is being used, how their data is being used, which innovation their data is being used for, which research their data is being used for.  And they have an opportunity to withdraw their data if they’re uncomfortable with any aspect of research.

Maili: I was just going to say something else about consent models.  When we’re thinking about different forms of consent, like dynamic consent, it’s also important to consider the accessibility of those, lots of those models would rely on the internet and people having access to laptops or phones.  And so when we’re exploring those models, we need to make sure that people have access, and if they don’t have access that there’s other ways that that sort of consent model might be able to be replicated, or there is an alternative way, so that people aren’t excluded through that.

Naimah: Is there a question around language barriers as well with the consent models?

Maili: Yes, when verbal consent is taking place, the same problems of language barriers are there within the online version.  You know, how do you make sure that things that are translated, and translated well as well?  Because genomics is a complicated area with lots of jargon and complex language.  So how can we make sure that we translate that language in a way that’s done, where the meaning is kind of translated as well.

Trupti: The language thing was something that came up within some of our community workshops.  And I think one of the things that really came out was that genomics research itself has so much technical language that often you simply cannot translate the word into other languages.  And different ways in which you can convey information, so that you're still making sure that you're getting informed consent from participants I think is really important for these groups, beyond simply translating written material.  Whether that’s through analogies or visuals that convey information, I think that’s quite an underexplored area actually, within research more generally, but as a starting point genomics.

Naimah: And did any of those community groups identify any preferences for what way they wanted to be communicated with, for consent and things like that?

Trupti: I mean, certainly having online consent was a huge barrier.  So the idea that you log into a platform online in order to provide your consent to something wasn’t something that people were that comfortable with.  Especially since these participants are often very reluctant to take part in the first place, so you're almost creating a barrier to them as well, it’s an extra thing that they have to do.  They did feel that consent should really be in person.  They also preferred the idea of being able to discuss genomics widely within less formal settings, so outside of healthcare settings, or outside of research settings.  Because it meant that they felt that they were primed for the questions that they might have.

One of the things that I was going to add is actually for genomics in particular, I mean, I mentioned before about when people decide whether or not they would like to consent to take part in genomic research..  They feel like they’re not just consenting for themselves, they’re also consenting for people within their network.  And so these are people that they would consult probably as to whether or not they should or shouldn’t take part.  And so when you are making that decision and you're having those consenting conversations, whether that be within a research setting or a healthcare setting, it’s important I think for people to understand that those decisions have been taken not just by an individual, they are actually reaching out to a much wider range of people within their own communities.

Naimah: And is there something around that these decisions are often made with family members as well?

Trupti: Yes.  So in situations where there are people from some cultures who are much more likely to take part in cousin marriages, these particular populations have scientifically been shown to have much higher likelihood to develop genetic conditions.  Now if that is the case, that can lead to a lot of stigmatisation, and it can proliferate a lot of discrimination that these population groups might be facing already.  So I think that’s something to be considerate of.  And it might influence their decision making as to whether or not they or their family members should or shouldn’t take part.

Niharika: Yes, just to add onto what Trupti and Maili actually said, while language plays a very important role in terms of consent, how consent is being taken, it also depends on the setting.  In our areas where we engage with communities, usually the consent, or consent regarding medical research or genomic research is taken via the GPs.  And the GP services here in our areas are so overwhelmed at the moment, there are long waiting lists, like three months.  And when people actually get through the waiting list and go to their GP, they’re so done with the process of waiting that when their GPs ask them for consent, they just either feel that they need to succumb to the pressure of, okay, giving the consent.  Because there’s this skewed power dynamic over them as their white man or white doctor asking for the consent.  But also, they don’t know what exactly to do in that moment, they’re very frustrating from the long waiting line.  And they feel they’re okay, they might need a little time to sort of cool down, go back home, look at the consent form, what is it about?   

And in South Asian settings usually the decision making is done in family setting, where you consult your families.  And when we spoke to older South Asian women and asked them how would they give their data and why would they give data, they mentioned that they would give data because their children or husbands have advised them to do so.  So yes, it’s important to see the setting of where the consent is being taken, who is taking the consent, and if they have enough time to think about it and go back and give their consent.  Also, it came up during the workshops that it helps if the consent is being taken by someone the communities already trust.  So having accredited community champions seek the consent.  So once they’re trained, once they have enough knowledge about genomic research and how it can benefit their communities, they’re able to better bridge the gap between the researchers or the research organisations and the communities. 

Maili: Yes, I completely agree.  And I was just going to add that it’s important that healthcare professionals are properly informed and open and aware of those different cultural or contextual dynamics within those consenting conversations.  So that they can properly listen and understand where people are coming from and give that time.  And I get that that’s difficult in pressurised situations, where healthcare professionals are under a lot of time pressure.  But that needs to really be built into that healthcare professional training over time so that carries on and people can talk about genomics in a really accessible way.  And that carries through as well to genetic counsellors who give results to families, they need to be able to do that in the right sort of way.  And they need to ask the right questions and understand the patient that they’re talking with so that that information can be translated or got across in the best possible way.   

And that’s even more important I think where there is a lack of diverse data that’s informing research and informing healthcare outcomes.  I think healthcare professionals should be transparent with patients about some of the accuracy of certain things or how different results might mean different things for different people.  And it’s really important that those conversations are had very openly and for that to happen, healthcare professionals also need to get the training to be able to do that. 

Naimah: Okay.  So we’re going to move on to talk a bit about developing countries.  Niharika, I wanted to come to you for this question.  Why would diverse communities benefit from research being more collaborative with developing countries? 

Niharika: So in recent times, we have witnessed growing diaspora in the UK.  And when it comes to collaboration with developing countries, there’s increased collaboration with these developing countries.  It can be a win-win situation for both the countries, for example, there can be increased innovation for these developing countries in exchange of information.  And at the same time, people in the developing countries, if they provide their data, they have the sense that they are helping their own communities who are living abroad. 

Naimah: You’ve touched on a few points already, but, Trupti, I wonder if you could talk about the considerations we should have when considering international partnerships? 

Trupti: Yes.  So one of the things that Genomics England has tried to do in the past and is still trying to do is increase the number of international academics that can have access to our biobank.  Now we already know that internationally, especially in developing economies, there’s often a lack of data purely because the resource to do things like whole genome sequencing is so expensive.  The resource to even have or host a biobank itself is so costly that the barrier to even developing the infrastructure is so high.  So one way that we’re looking to encourage innovation within those settings is actually to allow access through particular partnership agreements to academics who are based abroad.  Now obviously that means that there’s a benefit for them in terms of being able to do the research in the first place.  But one of the things is that as a biobank we’re also known for being a very highly secure biobank, compared to others.  So that’s something that as a data store people actually highly respect, and in particular, a lot of the data regulation within the UK is highly respected by other countries.   

One of the things that we have seen happening recently is that essentially some of our data security laws and data protection regulations are being reproduced in other countries as a way to ease working with research datasets across geographic political boundaries.  When it came to engaging members of local primary communities they have three primary asks when it came to the international partnerships that we might be developing in the future.  One of them was that at the very least there would be tiered pricing.  If we ever came to a situation where we were charging for access to our data, that pricing should be tiered to address the fact that if you are someone based in a developing economy, your access to financial resource to do research is much lower.   

The second ask was that there’d be some way for us to foster collaborations.  Now, whether that be led by an academic who is based abroad or an academic based in the UK was up for debate.  It was more that those collaborations have to continue and have to be enabled in some capacity.  And then the third thing that was a big ask was actually around IP sharing.  So what happens to the financial benefits of doing this type of research?  And also, more equitable basically knowledge sharing across these regions was what was asked.  So what we’re looking at in the near future is whether or not these principles could be used in order to guide some of our international partnerships’ work. 

Naimah: And I think just on that point you raised about fostering collaborations, Maili, I wonder if you could comment on how we could foster collaborations between the researchers and the communities that they serve? 

Maili: Yes.  I think here is when engagement is really important, and we need to get researchers and communities speaking to each other, to have some sort of meaningful dialogue that doesn’t just happen once but is embedded into whole research practices.  So there’s many different opportunities to feed in and that practice is shaped based on the feedback the researchers receive.  I think engagement is a really amazing thing, but it does need to be done well, and there needs to be clear outcomes from that engagement.  So people need to feel that the information that they’re giving and the time that they’re giving is respected, and that those practices do change as a result of that.  So I think we really need to make sure that engagement and practices are done well.  And I was just going to say something on collaboration between different researchers.  When researches are happening across borders, it’s really important that that’s done in a really equitable way, and that those conversations are had between different researchers to figure out what’s going to work well.   

We need to avoid instances of things like helicopter science, and sometimes it’s called other things.  Where researchers for example from the UK would go into a developing country and undertake research and then leave, taking all the benefits with them and not sharing them.  And that’s something that we really need to avoid, especially in the UK, we don’t want to exacerbate colonial pasts.  And I think it's really important in this context that those benefits are shared with communities.  And again, we can do that through engagement and understanding that relationship and making sure that collaboration really is collaboration, and that we can provide things that maybe others need or want in the right sort of way. 

Niharika: Just to reiterate our communities are still haunted by the colonial pasts.  There’s always this constant fear that our data might be misused, there might be data breaches and we won't be protected.  And your DNA data contains a lot of personal information, so there’s constant anxiety around your DNA or genetic data.  So it’s important that the researchers maintain utmost transparency.  There’s a constant focus on flattening the hierarchies, where you sort of bridge the power gap between the researchers and the communities.  And it can be done through, again, as I mentioned before, having community champions on board who understand the communities better, who are constantly in touch with the communities.  And they provide that sort of semi-formal settings, where they know that where they’re in constant touch with the authorities or the GPs or NHS, but also at the same time have very good relationship with the communities.  So this is something that should be taken into consideration.  And then just be cognisant of the cultural values, and not have very imperial ideas when you sort of approach communities. 

Maili: I think this becomes even more important as genomics continues to evolve and new genomic techniques are developing.  For example, with things like polygenic scores, where we can look at people’s genomic data and predict how susceptible someone might be to developing a certain disease or trait or outcome, in relation to the rest of the population.  Those are developing, and people are interested in them, but the data that they’re based off again is that European genetic ancestry data, and therefore is not accurate or applicable to lots of communities.  And it’s not just genes that we need to be aware of, it’s people’s environments, and that data is really important to integrate with things like polygenic scores.  I think we need to really address these issues now and make sure that as genomics develops that these things aren’t perpetuated and existing health inequalities aren’t continued to be exacerbated. 

Naimah: Okay, we’ll wrap up there.  Thank you to our guests, Maili Raven-Adams, Niharika Batra and Trupti Patel, for joining me today as we discussed the ethical, legal and social implications of genomics research for diverse communities.  If you’d like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app.  Thank you for listening.  I’ve been your host and producer, Naimah Callachand, and this podcast was edited by Bill Griffin at Ventoux Digital.

For Sickle Cell Awareness Month, our sickle cell Patient Voice Group discuss their lived experiences with sickle cell, shedding light on how organisations need to be considerate when engaging with patients. They emphasise the need for genuine engagement and transparency from researchers, while highlighting the importance of building trust within communities that have historically been overlooked. The discussion looks to the future, advocating for more personalised support, better treatment options and a stronger focus on the diverse experiences of those affected by sickle cell.

Marie Nugent, Community Manager for the Genomics England Diverse Data Initiative co-hosts this episode with Natasha Gordon-Douglas, sickle cell patient advocate for the Genomics England Diverse Data Initiative and Lead Mentor at the Sickle Cell Society. They are joined by Oleander Agbetu, who cares for her son with sickle cell, and is also a member of the Solace sickle cell and thalassaemia support group board, and Jayson Kupoluyi, sickle cell advocate and volunteer for the Sickle Cell Society.

The episode also features insights from some of the other members of the Patient Voice Group; Hazel Attua, Samuel Chuku and Zainab Garba-Sani.

The Patient Voice Group are a group of people affected by sickle cell who share with Genomics England their expertise, based on their lived experience, to inform our sickle cell programme within the Diverse Data Initiative.

"If we as parent/carers and advocates and all the rest of it can even make a little slight difference to someone’s care, that’s what I want to do. That’s why I’m here."

You can download the transcript or read it below.

Marie: Welcome to Behind the Genes. 

Natasha: I think the fact is that people do want to hear from patients, and they do understand that actually you need the patient’s voice in order to make things better, and not just be in a room where you’ve got all board members that think, “Okay, this is what is good for the patient.” No, actually, they’ve got the patients there to help support that voice, and saying, “Well actually, this is the reality,” rather than what you think might be the reality. 

Marie: My name is Marie Nugent and I’m the community manager for diverse data at Genomics England. I’ll be co-hosting today’s special patient takeover episode of Behind the Genes with Natasha Gordon-Douglas, who is a member of our sickle cell patient voice group. On this episode, we’re going to be speaking to two people who are also part of our patient voice group, Oleander Agbetu and Jayson Kupoluyi. Today we’ll be discussing what it’s like to live with sickle cell, and how organisations who wish to engage with patients need to be considerate of what is going on in people’s lives, and what good advocacy and support for patients who want to be involved in research looks like. If you enjoy today’s episode, we would love your support. Please like and share, and rate us on wherever you listen to your podcasts. 

Welcome everyone, thank you very much for your time today to talk about the patient involvement and engagement work we’ve been doing as part of our sickle cell and genomics programme at Genomics England. My name’s Marie, I’m the community manager for the diverse data initiative, and I am really involved in doing the sickle cell engagement work. I’m going to pass straight to Natasha now, who’s going to be my lovely co-host for this podcast. So, over to you, Natasha. 

Natasha: Thank you, Marie. I’m Natasha. I would say my background is nothing to do with the medical side. My background is in marketing and the corporate world. That’s how actually I got introduced by John James, because I actually got him into our workplace to do a podcast about sickle cell. So, you know, just – I’m working in an environment, which obviously – it’s about people understanding about my illness, so I actually got him in speaking, and then he mentioned about a project, “Oh, you might be interested in this.” So, that was kind of the introduction I got from John James. But as I said, doing patient work and engagement stuff was completely new to me, so this is my – I’m a rookie, I should say. But I feel like now after the two years, I know now, I understand [laughter]. But yeah, that’s kind of a quick background. And how I got introduced to Marie is from John James at the Sickle Cell Society. 

Marie: Great, thank you, Natasha. So, coming straight to you now, Oleander, I think it’s a bit different for you. So, you joined this particular group not too long ago, but from what I know, you’ve been doing this kind of advocacy work and engagement work for quite a while. So, tell us a bit about yourself. 

Oleander: Well, I’m a parent/carer of a teenager, young man with sickle cell, and I think I’ve been part of the Solace sickle cell and thalassaemia support group board for more than ten years now. And what we do is we support patients through our WhatsApp group, as well as through inviting different people to come and talk. We’ve had doctors, nurses, etc. And I have supported people who have called me personally to ask me questions, from advice, for help. Also written a letter to the hospital, which we are now working on with the hospital itself, to try and get things moving and make improvements for the patients who are actually patients there at Homerton Hospital and Royal London Hospital. 

Marie: And then over to you, Jayson. So, similar to Oleander, you joined this group fairly recently actually, but just tell us a little bit about the kind of work that you’ve done before. 

Jayson: My name’s Jayson Kupoluyi. My background is totally different from the sickle cell background. Because of the plight that I have with my health, I now decided that I wanted to make a change, so I – unbeknown to me – I didn’t know what advocacy was. I just – when I meet people, I ask them questions, and, you know, thankfully enough, they really try and help and support in terms of advising me and those kind of things. So, I took that advice on board, and through the years I’ve met fantastic people, i.e. Oleander and her son. I met her son during a trip – we took the kids to a trip for a week for self-discovery, self-awareness, teaching them how to cope, and probably to see where – you know, try to make them open up. 

So, I now decided to volunteer for the Sickle Cell Society and give them seven years of my time, in which I’ve met fantastic kids and fantastic people. And through that, I’ve learnt to be able to teach people and the kids under 16 – well, I’m teaching from 26 year olds down to 13 year olds on how to advocate for themselves in hospital now. I teach the adults how to fill in application forms for PIP. I also write complaint letters and help them deal with complaints. And I also – sometimes I have the chance, from Royal London and Queen’s Hospital, to enter and view the situation, and ask information from the patients, from the nurses, carers and things like that, to be able to compile my own findings. And all in all, it’s been rewarding, because I just wanted to give back. 

Marie: That’s incredible, you know, because something that we’ve been talking about more recently as part of our sickle cell patient voice group is this idea of advocacy, and I’m just reminded that I’m with a great group of people to actually explore this because of the experience that you’ve got, so this is wonderful. Now, you’ve all just said you’ve got varying like degrees of previous experience of being part of advocacy work. Natasha, I’ll come straight to you, what were your initial expectations as to what it would mean or look like to be part of like a patient voice group?  

Natasha: To be honest, very sceptical [laughter]. I was like, “What are they really going to – are they really going to take our voice on board, and is it just another tick box that they could say, “Okay, we’ve funded a group for you to – with sickle cell,”” and I was very, yeah, sceptical. But actually I would now advocate for everybody to be part of a patient voice group. I think it’s so important. And the collaboration that happens with all these different organisations as well that you open up your mind to – ‘cos I didn’t know – you know, especially for this particular project that we’re working on, you’ve got the James Lind Alliance, never knew this organisation existed. I think the fact is that people do want to hear from patients, and they do understand that actually you need the patient’s voice in order to make things better, and not just be in a room where you’ve got all board members that think, “Okay, this is what is good for the patient.” No, actually they’ve got the patients there to help support that voice and saying, “Well actually, this is the reality, rather than what you think might be the reality.” 

So yeah, I would definitely champion anybody regardless, even – yeah, you’ve got sickle cell, of course, but any kind of illness, if there’s any kind of projects, trying to get involved, to really be able to try and shape what can happen. Because, you know, I guess what we’re working on at the moment, the opportunities for development within sickle cell are endless. And yeah, it’s just being part of that steering group, part of that voice to actually make change, especially with sickle cell. You know, it’s one of the ones that has never had anything – hasn’t had change for I don’t know how many years - I’m going to give away my age, for at least 40-odd years, I’ll say [laughter]. But yeah, so from what I can see, it’s slowly now changing and we’re in that wave, and I’m so excited to be part of that. 

I know Oleander, so you with your son, you’ve obviously seen the kind of – if there has been change for you. I guess for me as a patient, I might see it slightly differently, whereas you as a carer, a parent, you might see it completely differently. So I guess for you, what would you say for a person who might be considering joining a patient group or a parent/carer group? 

Oleander: I too was sceptical at first, but at the same time I can say that I’m really happy that I have been involved, because it means that all the information that I find out about that might be relevant to other parent/carers, I can pass that on, and vice versa. Any questions that they might have or issues that they might be going through, I can also get those considered. And I just think that it can be quite sad when a patient goes into hospital and they are on their own, they don’t have anyone with them. And so for me, for example, when my son was in paediatrics, and I’m sure the two of you would also know that, the treatment is just very different to when you become an adult. I could see from my son’s face, he just was not impressed with the adult care at all. And he more or less says, “Mummy, I’m not coming back to hospital unless it’s really like a dire situation. I just don’t want to go back.” And that’s quite sad because really we’re supposed to be able to support our loved ones in hospital. When they need the care, they absolutely need the care. 

I actually spoke to a parent today of a young man in hospital right now. His PCA was failing, which is, you know, the pump that gives the medication, right? And they actually asked her, “Is he still in pain?” If he’s been put on a PCA, how can you ask that question? So, you know, it’s so good that she was there to advocate on his behalf. He couldn’t even talk. And, you know, I know for my son also, when he’s in really, really deep pain, he stops talking, just doesn’t talk. And if he’s there by himself, it’s a real issue. And so, you know, I think from that point of view, all of these kinds of stories are really important to bring to forums like this, so that people can understand that of course, yes, it first affects the actual patient themselves, but it has a knock-on effect for the families, and the carers and the people that are involved with that person’s care. So, if we as parent/carers and advocates and all the rest of it can even make a little slight difference to someone’s care, that’s what I want to do. That’s why I’m here. 

Marie: Thank you so much, Oleander. I think that’s a really powerful story as well, and it just shows so – I couldn’t help but think, as you were talking there, about this idea of – we use the word community quite a lot in this kind of engagement space, but I must admit, you know, I’ve been working in public engagement with health and research for well over ten years, and I must say that I really felt the sense of community in this sickle cell space, particularly with patients and the wider sort of community, and that feels like it’s a really important part actually. And it kind of speaks to what Jayson mentioned about, you know, he’s now reached this point in his own life where he wants to be actively kind of contributing back to the community. So, I’ll come to you now, Jayson. Again, what was your expectations about joining a group like this, and what were you thinking when you joined? And how has that maybe transformed now? Or potentially not? How has your experience been so far? 

Jayson: It’s been great actually, pleasant people, likeminded people working towards a common goal. When I first heard about this group, I said to myself, “Do I have space for another WhatsApp group?” It’s not because I don’t have space on the phone. It’s because getting calls in the middle of the night at the same time – and you can’t turn it down sometimes, especially if it’s in the family, ‘cos I have these people – I have - you know, it’s in our family and it’s very, very rampant. And when you say community, you can have a mother of your nephew, your niece call you, knowing fully well that you’ve gone through that, this sort of thing, what’s going on, blah-blah-blah, “Okay, this is what you need to do. This is what you need to do.” Then getting to the hospital is another ballgame, do you understand? And you just have to say, “Okay, you know what, if I take a moment of my time and say, “I’ll see you in the morning…”” I’ve had two incidents that I didn’t make it, and it’s a guilt trip to me, because I was thinking, “Hold on, if I had gone…” And then I was okay – if I wasn’t feeling okay then, yeah, but I was okay. I was just tired.  

And when I started, I was a one-man band, and I realised the last 20 years that it’s definitely not going to work, hence the community comes in. And the time I tapped into this community, I met people – “Okay, so, you could help me out, you could help me out, you could help me out.” And the more I meet people, the more my voice goes bigger, louder and reaches more people that I want to reach. So, when I first met Hazel, she was in pain, so I called her and I was like, “Madam, you don’t know me, but I know that you’re in pain, are you okay?” And she goes, “No, I just wanted to sit down.” I just sat down beside her, didn’t speak to her, just sat down, and she didn’t utter a word, but she came to a conference and I’m thinking, if you’re in pain, you know, okay, I’m the same – I just started explaining myself to her, “I have this, I’ve gone through this,” blah-blah-blah, and she was looking at me and she was like, “You don’t look like (inaudible 0:15:54).”  

So, meeting and coming to this group, my expectation was a bit elevated actually because, when I was speaking to Hazel, she said, “No, Jay, seriously, you need to be in this group because we need the other…” And I was like, “Not another one,” and blah-blah-blah. Hazel said to me, “Can you join the Solace group?” I was like, “Who’s in it?” She goes, “Oleander.” I was like, “Oleander’s good.” And everybody keeps on calling me, and I do appreciate that people want my advice sometimes, but this health is very precious to us. I am looking forward to greater things with this group. I am looking forward for us to reach some targets, some funding, some people out there, to be able to change so many things. And any time I see a sickle cell person in good health, no pain, no nothing, I give myself thumbs up. You don’t want to see anybody in that kind of pain, and people don’t recognise or have that empathy to share or say, “Just another sickler.” 

Sickler, that’s a word, hmm, I don’t like it. So, whenever I go to hospital, Queen’s or Royal London, they know, “Jayson, are you here to cause problem?” “As long as you answer the question, I will be fine. As long as we’re okay, I’ll be fine.” And, you know, we’re now friends. In the midst of adversity, we’re now friends.   

Marie: There is just so much I think in what you’ve just said, and I think that again something that I’m really struck by – so obviously, you know, I don’t come from any lived experience. I didn’t have people in my life that I knew that had sickle cell before starting to work on this as part of my job. And something that I’m really struck by is, first and foremost, from the No One’s Listening Report, the quite staggering evidence that, as a community of people, people living with and affected in some way by sickle cell are very neglected, and there’s all sorts of complex layers of like challenges and difficulties that people have to deal with, and it seems to come from all sorts of places and all sorts of kind of parts of life. 

I was just really struck by this really daunting situation actually to be put in. As someone who’s part of, you know, let’s be honest, quite a sort of – maybe quite far down the road in terms of direct benefits, like piece of work – so we’re here, I’m part of an organisation that is interested in supporting research and providing good quality research data, and research is a really important part of this whole system, but again it’s something that maybe will take five, ten-plus years before you’re seeing any direct benefit from in terms of the data that we’re creating.  

But something that I’m really struck by is this idea of, if we know that there’s going to be maybe a bit of a delay in the kind of benefits that we can bring to patients through the data that we’re generating, how can I try and build in as much benefit right now for the people that we’re engaging with and we can bring into this work right now? And that’s something that we’ve talked about and we’re about to initiate a bit of a project around exploring a bit further, but I just wonder if I can now come to you all and get your thoughts on what can organisations like Genomics England or other research based organisations – what in your view does being a good supporter or a good advocate for people living with sickle cell – what could that look like from a research organisation in your view? I’ll come to you first, Oleander. 

Oleander: I think a really massive thing is to support the removal of barriers. There’s so many people who would love to get involved with this, that and the other, but actually the barriers are there and the barriers are real. Even like from a personal point of view, the thing I was interested in attending, I can’t. It’s just not within my means. So, things like that are really important, because most people who are living with sickle cell, we are from marginalised groups. We’re from groups that are not known to be flushed, and we need the support from – you know, if you really want our help in terms of research and so on, we absolutely need your support and your help to provide you with that research and that help. So, it’s real. Giving someone a £20 voucher is nice and dandy, but actually if they’ve had to pay for whatever, accommodation or travel costs and all these things, they’re out of pocket before they even start. 

Marie: Yeah, this is something that we’ve been talking about recently, isn’t it? I know that organisations like ours do want to do better, but sometimes there’s just that not quite as good an understanding as to what these barriers really look like for people. Over to you, Natasha, what do you think about that? 

Natasha: There’s a couple of things I wanted to pick up on. One is definitely, yeah, the barriers. It’s funny, I was at a hospital this morning and I was talking to one of the consultants. He asked me the question, which I thought was quite weird, but he asked me, “Why do you think that sickle cell patients have to pay for prescriptions?” Like that alone, prescriptions, we’re on medication forever, you know, from the moment you’re diagnosed, which for me was at six months, so in my entire life, and you’re paying for prescription, that’s going to keep happening over and over, and you’re just – you know, there’s people, because of their sickle cell, they can’t work. There’s, you know, barriers of not being able to work. And then you’ve got potential – you apply and say your disability, and sometimes that’s not even taken on board either. So, you’ve just got these barriers in place that just make living day to day so exhausting, so tiring, and basically you’re fighting those barriers at every – you think you’ve passed one, you’ve come onto another. 

And I guess also the research side, which – it’s funny because I would say, when it comes to research, it’s fantastic, yes, that organisations like yourself are looking into it, but actually sometimes it’s not even – you can’t make the change where it’s going to matter immediately. It’s literally the frontline, you go into hospital and A&E, that’s your first barrier is trying to just get some pain relief or get any treatment. You’re sitting there for four hours. Four hours in pain for a person with sickle cell, that can really, you know, make things worse. And that’s the kind of – you kind of want the immediacy – like the frontline, those kind of things to change. And of course, yes, we do want more research and we do want people to take part, but it’s those things where you might not necessarily have the power to make those changes immediately that people will be willing to take part in research like this, because you can’t even just get the treatment that you need from the moment you step into a hospital. 

That’s kind of what I was thinking of as you are speaking about this. I’m like, you know, yes, this is great, but we just need sometimes just going into hospital to make it easier. Like what Oleander said, it’s unfortunate that the persons being asked about their PCA, if they’re in pain – well, what do you think? Like that’s just the basic [laughter], you know. It’s kind of like, how can you ask that question and you’re a healthcare professional being on the frontline? And that’s the worst. It’s the frontline staff sometimes which actually need the education. So, some of this research, it needs to go to education in these staff actually, you know. That’s maybe an area that needs to be sorted.  

Marie: For me, I completely have a whole new deeper appreciation for almost seeing people as the whole, how you work with the person. And it’s never been clearer to me - as I say, you know, in ten-plus years’ experience of doing this kind of work, it has never been clearer to me how important that is than now I work on sickle cell and how important that is. And I think that actually you’ve touched on a really important point there, which is that, you know, I know for sure that there’s incredible work going on through NHS England, through the inequalities workstream and in response to the No One’s Listening Report. There seems to be, you know, a huge increase in sort of focused action being taken to address a lot of these challenges that are being brought up in our conversation now.  

But actually, what you said, Natasha, did kind of really hit the nail on the head a little bit for me, which is that actually we kind of still look at this as kind of separate organisations, like, “Well, this is my bit and that’s your bit, so you stay over there.” And I think that something that we’re trying to start working towards through the Sickle Cell Society is actually how do we bring together a better sort of alliance of work and of people who are across research and healthcare, because these things feed into each other, right? So, how can we do better to sort of show that we are all aligned, that there isn’t just this one person or one group over here looking just at this little bit and then there’s a completely separate group, that we are all actually united in our, you know, intentions here to really improve the lives of people that are living with this condition. But of course, there’s just so much work to do, isn’t there? I think that’s another overwhelming thing, that everything needs to be better when it comes to sickle cell. 

Oleander: The thing I wanted to just add to this whole talk about what researchers can do in terms of supporting advocates, etc. Two things, understand that there is an issue for trust from our communities, because we’ve been burnt. And the second one is, we need transparency. So, be real when you talk to people about the information you’re gathering, what you’re going to do with it, how it’s going to impact the research, timetable of whatever’s happening, all of those things which will help people to gain more trust. 

Natasha: Yeah, Oleander, that’s so – yeah, I think definitely, that’s been echoed throughout this whole project, hasn’t it? It’s always about gaining that trust, because it is a case of, is this another where we’re going to have support and we’re going to be let down, or, you know, lied to, whatever you’re going to find out. And trust is a huge part of that, definitely, yeah. I think, yeah, definitely. Thanks Oleander for saying that, it is.  

Marie: Yeah, thank you all. So again just to say that I’m always blown away by just how generous you all are actually with what you say and with what you share, and with the messages that you’re ultimately trying to get across. And it’s very humbling, you know, to be able to work with you all, ‘cos you all are so incredibly passionate and driven, despite so many challenges, and it is nothing but inspiring. So, I can see absolutely why, you know, people living with sickle cell, for example, are called warriors, because you need to have that sort of fighting spirit to just keep going, and I have nothing but, you know, boundless like respect and admiration for people who are able to do that and contribute to the community in the ways that you all do.  

And I just think that again, you know, so talking now back to this idea of how research is set up, you know, I myself am part of an initiative that’s been, you know, initiated and only kind of guaranteed funding for this kind of iteration, for three years. It’s very difficult to sort of initiate and establish really good long-term relationships, and have like a longer term strategic sort of way in which you’re bringing in people and taking that long sort of like approach to building relationships, but it’s something that I’ve tried to be really mindful of actually, and to address a lot of the things that you just mentioned. 

You’ve heard us refer to other members of our patient voice group. Let’s now take a moment to hear from them. 

Samuel: Hello, my name is Samuel and I’m from Leicester. I have had the great privilege of working with some amazing people in Genomics England over the last few months, to hopefully one day be a part of something that takes down this condition that I struggle with known as sickle cell. Since John James of the Sickle Cell Society introduced me to Marie from Genomics England, there has been a door opened where the voice of a person dealing with the condition matters and holds weight, to help know what is required to further improve matters for people dealing with said condition. Hopefully, after reading the blog and hearing this podcast, you will know more about the work we’ve been doing, and feel as encouraged as we do. We don’t just want to stop here. There’s a long way to go, and we need all the help we can get to reach our goal together. 

Hazel: Hi everyone, I’m Hazel. I hope you enjoyed the podcast. Now we’re not done just yet. Keep your eyes out for our sickle cell and Genomics England patient takeover blog, where Natasha, Sam and I take you through what we’ve been up to and the future of genomics.  

Zainab: Hi, my name’s Zainab and I co-chair the Genomics England diverse data advisory board. I also have the pleasure of being part of the patient engagement group for this important piece of work. I’ve been a sickle cell advocate since before I even knew what advocacy was. As a child with sickle cell, I was exposed to different ways to help the community pretty early on, and have loved working with others to transform care for the better. Today, I hold a number of advocacy related leadership positions, including being a trustee of the Sickle Cell Society, chair for NHS England’s patient advisory group for sickle cell health inequalities improvement, and a member of faculty for Medscape’s committee on rare diseases. I also contribute to global sickle cell policy, practice and research. 

I’m super excited about the work we do with Genomics England because I think they’re a blueprint for what good patient centred work really looks like. My background is in health policies specifically related to research and innovation, so to see sickle cell being prioritised in this space is really special to me. We have an incredible opportunity to advance equity through research and innovation, especially related to genomics, and I myself am lucky to experience the transformative power of regenerative medicine. I’m excited for this group to continue to advocate for and enable better access for such incredible science. 

Marie: We’re very lucky to have such a wonderful group of people who are part of our patient voice group, and I hope you enjoyed meeting them. Just going back now to sort of what can be achieved, and if we, say, come back together in a year’s time, knowing the kinds of things that we’ve just talked about briefly that we maybe want to look at – we’ve mentioned things like doing more family sessions, looking at how we can engage young men in particular, doing what is needed to kind of give that really strong message about how you support people to be part of these kind of patient advocacy roles. But what would you really like to see that we’ve achieved together by say this time next year? I’ll come to you first, Jayson, this time. 

Jayson: Thank you very much. Going straight to the point, I would like us to have more one to one with the patients and family in terms of – mainly I think to move towards the male, because, you know, I’m a living experience of some of the things that’s happening, and put the awareness out there, and let them know that – not to scare them, but to give them adequate information to be able to arm and tool themselves for a better life for themselves, a better respite for themselves, and a better understanding of the situation. I know if sickle cell patients have enough time at work, at uni, at school, during their exams, they will achieve great results, and I would want that to be one of the forefronts of this campaign, to make sure that, you know, the male side – I do know a bit of the female side but I’ll leave that to Oleander and Natasha, but the male side of what they should expect, and how to – if I could put this in (inaudible 0:33:59), I am making myself a role model for them, because I have leapt over barriers and over so many expectations, and if I could do it, with the science and the support we have now, they can double it, they can triple it, they can do more. My journey hasn’t ended yet, but before it does, I want to tap into every organisation to hear more voice, to just give me five minutes to hear my voice. 

Marie: Thank you so much, Jayson. I can’t think of a better role model for young men who are dealing with this than you, so it’s brilliant to see your dedication to that. Over to you, Oleander, what would you like to see – if we’re here together in a year’s time, looking back on what we’ve done over the last year and what’s been achieved, what would you really like to see? 

Oleander: I’d like to see sickle cell actually being taken seriously, that people don’t make assumptions that, “Oh, it’s just a small, you know, blood thing, it’s nothing that deep, nothing that big,” whatever. Because the reality is, for a lot of indigenous people here, the majority ethnicity in this country, sickle cell is spreading because more people are mixing, more people have come over, refugees, economic migrants, etc, and mixing, and so they will find that actually it isn’t just a tiny minority of people. We’re told it’s 17,000 people in the UK, but actually that number’s going up. So, you know, it is a bit of a shame that it takes it to affect the ethnic majority in this country that anything would change, however this is the reality we live in. So for me, that’s what I would like to see, that sickle cell is taken seriously, that we’re not just stuck with one or two authorised drugs for people living with sickle cell, and actually one of them is not even a sickle cell specific drug. 

So yeah, we want sickle cell to be taken seriously, and so that people can actually trust the process and trust the people who are genuinely trying to research issues to do with sickle cell, so that we can make the difference that we need to make for people’s lives. 

Marie: Thank you, Oleander. That just reminds me that, you know, hopefully – so, one of the projects that you are also involved in that we’re doing is – and that’s been already mentioned, the James Lind Alliance and the Sickle Cell Society partnership that we’ve got, the priority setting partnership. Hopefully, one of the things that’s part of doing that is that we do create that sort of focused priority areas, and that’s really strongly centred on the voices of people living with the condition, supporting people with the condition, whether they’re parents, carers, healthcare professionals. So yeah, I completely agree, you know, really putting it on the map, taking it seriously, raising the understanding, raising it as a priority, I think that would be great to see in a year’s time for sure. So of course, last but not least, over to you, Natasha. 

Natasha: Well, Oleander has literally taken the words out of my mouth. That is exactly what I would want to see in the next year, and to me, it can be done. There should be no reason why it can’t be, with all the technology, with all the advancements that’s happening. There is no reason why sickle cell should not be leaps and bounds with the information, with the project, of getting this information from sickle cell patients. It should come to a point where actually no one has to suffer from sickle cell because, you know, the – what’s it called, the medication, that one that’s recently come out, that’s way overdue. I can’t even believe it’s taken this long to just come up with that one, you know. The stem cell treatments and what they give as an alternative, it’s not good enough basically. And, you know, we had this new one come out – I say new one, but this hydroxycarbamide, it’s like that wasn’t even for us. It was all by mistake that, “Oh actually, this might help sickle cell, let’s see.” And that’s what’s the afterthought, and we shouldn’t be an afterthought. It should be a priority.  

And yeah, having that priority setting that we’re doing with the James Lind Alliance – it’s funny, ‘cos I remember, we had a call in our patient voice – I think he mentioned – I think it was something about maybe the questionnaire that we were going to give people, or – I can’t remember the particular thing which I said to you, you’re having trouble – you know, we’re underrepresented, there’s no data on us for a reason, and you had a template, and it’s like this template’s not going to work, because you have to approach it differently. Like you have to literally rip it up and start from the very beginning, because what you’ve tried to do in the past hasn’t worked, or, you know, the majority of people, especially in the European world, it works for them, great, but you’re coming to an underrepresented community and you’re thinking, “Oh actually, we can just use that thumbprint and put it on this.” No, you’ve got to start again. 

And I think it brings the importance of actually taking part in things like this, is that without actually knowing this, you would have thought, “Oh actually, people just aren’t interested, you know. Patients don’t want to know. They don’t want to give any information over to us.” But it’s like, well no, it’s not that at all, it’s just that you need to approach us differently. You need to, you know, understand what actually we’re going through before you can then try and fix anything or provide information, or get, you know, medication advancements. Like these things need to be done and the groundwork first, and not thinking, “Oh okay, we can just put a little plaster and that’ll heal that.” 

So for me, definitely, more options when it comes to treatment. And, you know, that we’re not the minority when it comes to data. Because especially with sickle cell, it affects different people in so many different ways, and they’re just trying to understand, “Oh, why does it affect this person this way but it hasn’t done it in this person?” And it’s just like, great, you’re asking these questions, but now let’s move it forwards. Like let’s not keep talking and let’s start the action. And that’s probably one of the other things is, I want to see the action. It’s the action now. You know, of course, if you want us to talk, we’ll talk, you know. We won’t stop, and we can keep going. But ultimately let’s actually have some movement. Let’s have an action that you’re – I say you as in you as an organisation, but wider, everybody that’s part of the process comes and says, “Look, this is what we’ve been able to achieve.” And, you know, then you know you have been listened to. A bit like Jayson said, you know, still not listening. Actually, now you can say, “Yes, we’ve heard and now this is what’s come from it.” So yeah, that’s probably I think for me the biggest utopia is that actually sickle cell just won’t exist. It’s done. They’ve been able to sort it out [laughter], it’s no longer an issue at all. But yeah, we won’t get to that next year, but, you know, hopefully eventually down the line there is that cure or change that they can do. 

Marie: I think for me, it kind of just brings me back to this point that there needs to be a united front in terms of like dealing and addressing with this. And also importantly, it needs to come from the community itself in terms of setting the priorities of what is done now, what is immediately needed to be done now, what can be looked at maybe a little bit later down the line, as there’s maybe a bit more information, a bit more understanding, a bit more knowledge to kind of maybe base some things on. But yeah, every time I hear, you know, people speak about all the various challenges that, you know, of course, come from their own lived experience and having to see how this affects their community, and yes, there are steps being made in the right direction, but I think we all probably agree that we could all probably be doing more to just improve the way we’re uniting this work, and we’re doing it in a way that is really coming from the community themselves and saying, “We want this to happen now and in this way, and this is what we want you to look at addressing.” 

We’ll wrap up there. Thank you to my co-host Natasha Gordon-Douglas, and guests Oleander Agbetu and Jayson Kupoluyi for joining me today as we discussed engaging people with lived experience of sickle cell in research and advocacy. If you’d like to hear more about this, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. I’ve been your host, Marie Nugent. This podcast was edited by Bill Griffin at Ventoux Digital, and produced by Naimah Callachand. 

In this episode of Behind the Genes, we explore the challenges diverse communities face in accessing genomic medicine. The discussion focuses on issues including language barriers, cultural differences, and socioeconomic disparities that hinder marginalised communities from accessing and benefitting from genomic medicine.

Our guests delve into successful strategies for engaging these communities in healthcare research and decision-making, highlighting the importance of building trust with groups that have historically been underserved or mistreated. The episode also emphasises the need for culturally sensitive communication from healthcare professionals and how meaningful community engagement can foster collaboration and trust within genomic research.

Our host, Naimah Callachand is joined by Aman Ali, a Community Ambassador at Genomics England and Community Engagement Manager at Our Future Health, Anna Smith, Child and Adolescent Integrative Psychotherapist at Rareminds, and Moestak Hussein who works for Bristol City Council in Public Health & Communities, working directly to build and imbed cohesion, inclusion and social justice approaches in her role.

"If we talk about co-production, true co-production is really creating a power balance where there’s no hierarchy. It’s an empowering model. It empowers both the researchers or the person that comes in, but also the communities that participate, and you all start on the same level, on the same outcomes and the same goals and aims that you want to achieve."

You can download the transcript or read it below.

Naimah: Welcome to Behind the Genes. 

Aman: It’s really important to engage community leaders who are really well embedded within the communities, who are attached to organisations or institutions which are well trusted in the community as well, so that we can get a wider perspective of how communities feel about genomic medicine and accessing services that we want people to engage with. 

Naimah: My name is Naimah Callachand and I’m Head of Product Engagement and Growth at Genomics England. On today’s episode, I’m going to be joined by Anna Smith, child and adolescent integrative psychotherapist for Rare Minds, Aman Ali, a community ambassador for Genomics England, and Moestak Hussein, community coordinator at Bristol City Council. Today, we’ll be discussing the disparities in access to genomic medicine amongst diverse communities. If you enjoy today’s episode, we’d love your support. Please like, share and rate us on wherever you listen to your podcasts. 

Aman: Hi, my name’s Aman Ali, I am an ambassador at Genomics England, a person very passionate about health research and ensuring that diverse communities are involved in health research, and I work as a community engagement manager at Our Future Health. 

Anna: My name’s Anna Smith, I’m a psychotherapist. I work in private practice and also with Rare Minds, who are a company who provide therapy to people with rare and genetic conditions. 

Moestak: Hi, my name is Moestak Hussein and I have a background in community development, and I’m passionate about tackling health inequalities, and building social justice and inclusive approaches to address health inequalities. I work at Bristol City Council in the public health team, and I’ve participated in the Bristol workshops around equity in research in genomics. 

Naimah: So, let’s jump in and first of all I want to talk about barriers to access for diverse communities. I want to talk about how there are language barriers, cultural differences and socioeconomic factors that impact access to genomic medicine for marginalised communities. Anna, I wonder if you maybe could talk to me a bit about this. 

Anna: Yeah. So, I’m talking about the traveller community, and we refer to this community as a GRT community, which is Gypsy, Romany and Traveller, so it encompasses people in the UK, people living in Ireland as well. And some of the barriers to accessing healthcare are a lack of understanding of culture. There’s been studies done where it says that people from GRT communities show up lower on all markers for poor healthcare and poor mental healthcare, and part of the reason for that is things like illiteracy. You know, you’re dealing with people who can’t read or write. They can’t read appointment times. They don’t have access to public transport. A lot of women don’t drive in this community, and also women are not very well supported within the community by the people who can drive and who can get them places, because it’s not seen as something that they need access to. Because the community is so closed, everything sort of takes place within the community.  

In terms of genomic healthcare, access right from the start of life, if people are not accessing healthcare right from birth, they’re not getting the genetic testing that’s needed, so then a lot of these things don’t even show up until the illness presents itself, and then accessing healthcare from there is really difficult. You know, it’s something that – it doesn’t happen a lot. Only 67 percent of people from the GRT community were able to get a doctor’s appointment when they needed it, compared to nearly 90 percent from other communities, and that’s through things like not having a fixed address. Lots of GPs don’t offer temporary registration, which means that if you are travelling, you do not have access to a GP, which is your first port of call if you need any access to healthcare. So, many people from the GRT communities are using A&E services in order to get healthcare, which – you know, they are not set up for dealing with long-term life changing conditions. They’re there to deal with what’s right in front of them and then they move on. There’s no sort of continuity of care. 

Naimah: Thanks Anna, that’s really highlighted a lot of barriers for the GRT community. And I wonder, Aman, if you want to come in now and maybe discuss some of the barriers that maybe the Muslim community might experience. 

Aman: Yeah, I think anyone involved in medicine or anyone who’s a doctor is really well respected in the Muslim community. That profession is something that every parent aspires for their children to get involved in. They at least want one of their children to be a doctor. Having said that, there’s this willingness to engage with the space, but there’s a lack of knowledge, which is a huge issue here. People don’t know what the word genomics means or genes, or understand DNA. Some of this language is a huge barrier to understanding and then eventually accessing some of the services that could be available to people from Muslim communities. Because when we speak about Muslim communities, we’re talking about a huge, diverse group of people from South Asia, from North Africa, from the Middle East, and they all have their nuances and different cultural experiences as well. 

Just to kind of point out maybe one or two, most people in the UK have grown up in the UK, where access to healthcare is free, whereas this is quite a strange phenomenon for people who may have not been born in the UK and then access healthcare services in the UK. And the context being here is usually they pay for healthcare in other countries, and whenever any public or free healthcare is provided, it’s usually seen as kind of not very good or suboptimum, or yeah, it’s not going to be very helpful for us. So, when they see free healthcare in the UK, there’s that kind of apprehension, “Actually, is this going to be worthwhile? I’m not paying for this, so it’s not going to be very much good for me.” So, those are some of the cultural nuances that certain communities where healthcare is not for free in certain countries that poses a barrier. 

Language in terms of speaking and reading is an issue. So, a lot of people, they may speak a language, but they don’t know how to read a language. So, even when services are translated – I, for example, can speak Bangla, but I can’t read or write Bangla, and not a word of Bangla at all. So for my parents, who can speak Bangla very well, their reading level is actually quite good, but I know that many within the community, they didn’t get education back home, and therefore reading and writing is a challenge as well. And then you have the issue of dialects. There’s so many dialects within so many different communities, so when a language is spoken or written in a particular way, if that dialect isn’t your mother tongue or a dialect that you’re familiar with, then that causes challenges to access as well. 

Naimah: Moestak, how do cultural beliefs and values influence attitudes towards genomic medicine within each of these different cultural communities? 

Moestak: I think Aman and Anna touched on it a lot, and it’s about communities being able to coproduce that historically hasn’t been there. The supremacy of certain communities to have a voice and be able to express how they would like to shape their healthcare, but also access to healthcare barriers have been part of having a barrier in access. And I think Aman touched on like even the term genomics, I don’t think it exists in particularly my community. I come from the Somali community, and I’ve tried to look at historical kind of words and terms. I mean, our language only got developed in 1973, the written language, so you can imagine that there’s a lot of gaps or there’s other terminologies. 

So, the cultural beliefs and values is also communities’ recognition to be driving their own health needs and priorities is not valued within those sectors such as healthcare. I mean, we’re still talking about holistic medicine. People go to their faith leaders in the first instance to have support around prayer. That’s not necessarily recognised by mainstream health provision. And I think it’s about how do we build on those strengths and how do we recognise that that is a really great part of communities. And it’s also tradition and customs within childbirth, from birth, understanding what children and young people and families will need. I know there’s customs and traditions for women to stay at home, for example, for 40 days, and those are the kind of traditions that could be built on. And I think it’s about making sure that the child doesn’t pick up bacteria or things like that.  

So, there is an understanding and knowledge within communities of genomics. It’s the awareness and the training around patient centred approaches are still missing, in my opinion. And I think that influences how people view genomic medicine. It goes back to the lack of trust and historic past abuses and cases, that communities has resulted in lower participation and a reluctancy to be part of genomic testing, but also that lack of understanding. 

Naimah: Anna, did you have something you wanted to add in there? 

Anna: What you were just saying about keeping it within the community, that’s something that we see with the GRT community massively is everything is handled within the family, and I think that’s not necessarily valued outside of that community. If you arrange an appointment with someone and the whole family turns up, it’s like, “Woah, what’s going on here? You know, how is this managed?” And it becomes a safeguarding issue, when actually that is how it's managed, and very often you need to get the whole family on board before you can start working with an individual. Because within the GRT communities, individuals do not exist outside of their families. Even what we’re saying about language, a lot of the GRT community who live in England now speak English, but the words that they use for mental health are very different.  

You talk about mental ill health, that translates as psychosis in the GRT community, whereas if you’re talking about depression and anxiety, somebody might say that they’ve got bad nerves. So, if you come up and say, “We’re dealing with mental health now,” people would say, “Well, I don’t have psychosis, I don’t have that, this is not an issue for me.” And it’s like you’re speaking different languages even though you’re using the same words. 

Naimah: From what all of you have said as well, it does sound like there are a lot of similarities in the barriers in each of the different cultural communities. 

I wanted to move on to ask about what strategies have been effective at engaging these diverse communities in healthcare research and decision making processes. 

Aman: There are a number of ways I’ve seen best practice take place in regards to kind of community engagement. The approaches have been one of two approaches. One, either inviting the community to come to your spaces, i.e. organising events or having opportunities where people can engage with your service. Or the alternative approach, which I think is actually more effective, is actually going to the spaces where communities are most familiar with. So, whether that’s holding a focus group at a community centre, at a church or at a mosque, or engaging in coproduction with a community organisation, to come together, to come up with an idea of how to best engage communities. And I also feel like there’s a difference between PPI, patient and public involvement, versus community engagement.  

And those are the two major approaches that I’ve seen when it comes to community engagement, and I’m a big advocate of community engagement, because you’re going into spaces which are authentic to the very communities that we are hoping to engage, but you’re going into an unfamiliar environment as opposed to bringing that community into an unfamiliar environment, where they might be a bit guarded with what they want to share and how comfortable they feel. So, those are some reflections on good practices in community engagement. 

And I think one of the key things that we need to do is understand who are the key community leaders within that community, ‘cos it’s one thing being within that community, and being able to speak about that community are two different things altogether. So just to articulate what I mean by that, I live in Luton, but I’ve just moved to Luton two months ago, so if you ask me about what life is like in Luton, I’ll be able to speak about my experience, but if I was to live here for 20, 30 years then I’d be in a better position to speak about how people in Luton live and what their experiences are like, and that’s two different perspectives you’re going to get. So, it’s really important to engage community leaders who are really well embedded within the communities, who are attached to organisations or institutions which are well trusted in the community as well, so that we can get a wider perspective of how communities feel about genomic medicine and accessing services that we want people to engage with. 

Naimah: Thanks Aman. I think you made a couple of really good points there, and I think you kind of have this overarching feeling of building trust, which is what Moestak mentioned in the previous question as well. I thought maybe now would be a good time to discuss your first responders project, Aman, if you could tell us a bit about that. It’d be good to hear the kind of developments from that community work. 

Aman: Yeah, so one of the ideas that came about from engagement actually that we had with some community leaders within the Muslim community, primarily some imams, they heard about the work of Genomics England, they heard about the work of research in particular, and they were really keen to get involved even further, but they were honest in saying that, “I know very little about this space. And it’s one thing for me not to know much, but then if I don’t know anything then I’m not able to then advocate for this within the community. So, two things you need to help me with. One, help me understand this space, but also allow me to then be able to advocate for services or information that my community can benefit from.” 

So, that’s where the inception of this first responders idea came about. The idea being that community engagement happened with some imams from all across the country, where we trained them to understand a bit more about genomics, and genomic healthcare and medicine, but also to be able to navigate a number of scenarios that they may face in the community. For example, there’s a mother who has been recommended by their GP to go see a genetic counsellor, but they’re really worried about broaching that conversation with their husband or their family, because of the challenges that they may face. So, how would you support someone in the community when that scenario comes up? Or for example, someone like Genomics England or Our Future Health or another organisation has approached you about a research study, and they want to engage your community, how would you have that conversation with that particular organisation, advocate for those health programmes within your community? 

So, we just presented a number of scenarios. But I think the main thing that we ended with was giving the imams in this particular incident the ability to signpost to services, be it helplines that are available for communities to access more information, or websites that people can access in order to understand more information about different issues to do with health conditions, or whether it be better understanding issues like cousin marriages or kind of accessing genetic testing. 

Naimah: That sounds like you’re empowering the leaders to advocate for healthcare and share this with their communities through this work. I wonder, Anna, is that something that you could do in the GRT community as well, like empower the leaders of the family to disseminate these healthcare messages, and how would we do that? 

Anna: Yeah, I think so. I think a lot of it would need to be outreach, and there are people out there who can help bridge that gap. For example, there’s a great team called Family Friends & Travellers, and if you get in contact with them and let them know which community you’d like to go into, they can help arrange, or they will come with you to go into that community. Because the GRT community, you know, is very mistrustful of anyone coming in, and rightly so. It was only in 2011 that they were included on the national census as an option to say you’re from that community, so I think there’s massive mistrust there of anyone coming into the community. 

So, if you want to engage the leaders of the families or of the communities, you’re going into a settled traveller site, there will usually be somebody who is in charge of that site, not officially, but maybe their family might be the biggest family or they might be the most important family. And there are people out there who will allow you to start to engage with that person, who can then disseminate the information. But it needs to be outreach care, and the information that you disseminate, it needs to be tailored to people who have left school at primary age, who don’t have the skills to read or write, or to manage appointments or read prescriptions, or have access to that type of healthcare. That’s where it really needs to be tailored. 

And I think confidentiality as well needs to be tailored a lot, because gossip and reputation and shame is huge in the GRT community, and if you are seen to be engaging with someone outside of the community, that is something that can bring a lot of shame to you and your family, so it needs to be handled really, really carefully. 

Naimah: Just to kind of go along with this theme of trust that you’ve all now mentioned, Moestak, I wonder if you could maybe comment on what strategies can healthcare organisations and researchers employ to build trust with these communities who have historically been underserved or mistreated? 

Moestak: Yeah, I think I mentioned earlier about the hierarchy of power around superiority and also mistrust of medical professional generally, and I touched there on how safeguarding concerns are triggered on not understanding cultural norms and practices within communities, and misconstruing that with safeguarding. There is generally that mistrust is there. And I think what Aman touched on there is really the importance of asset based approaches, and really building on transparent and really embedding transparent and inclusive practices from the onset. I mean, if we talk about coproduction, true coproduction is really creating a power balance where there’s no hierarchy. It’s an empowering model. It empowers both the researchers or the person that comes in, but also the communities that participate, and you all start on the same level, on the same outcomes and the same goals and aims that you want to achieve. 

And I think it’s important to embed those kind of approaches, and it’s Covid-19 – I mean, we took part in Bristol in King’s Fund research around the community champions model. It’s exactly that, about engagement, about community driving their own solutions, and being able to collectively collaborate, drive their health piece forward, but also increase the capacity of communities. We worked with clinicians who come from those communities, and it’s no surprise that the uptake of covid-19 vaccine increased as a result of working with those trusted voices.  

Quite often, those really effective programmes and engagement often are not funded adequately. They’re not sustained. And what happens is that we constantly are having to rebuild and restart, and that really does affect trust as well with communities. And when something works, why not build on it? And even now with that Covid-19 learning from the community champion model, the resource is not there anymore. It’s not valued anymore, sadly. That in itself is a risk, I think, in building the trust, but also the strength to continue that work and adapt in other ways around genomic medicine, and even increasing and diversifying the genomics data pool, helping communities understand and drive that. And that first responders project, communities being trained to capacity build and then being able to drive that within their communities, that’s the only way that we’re going to have effective strategies. 

Aman: I think adding onto what’s been mentioned, with regards to building trust, it’s really important to understand the motivations of communities, and to understand what messaging is going to resonate with different communities, and it’s going to be a different message for each community. You can’t have the same approach for all communities. A recurrent theme that I’ve come across when engaging different communities is this difference between messaging which is individualistic and then messaging which is about the community and more the collective message, and how that resonates a lot more with certain communities that I’ve engaged with, particularly within Muslim communities. And that’s something that I think is a bit untapped in regards to kind of any materials that are created, be it posters or videos or any content looking to reach out to communities. 

When we did some focus groups with some communities in Watford, who are primarily from the Pakistani community but also other parts of Asia in that region, the biggest response or biggest positive response that we got was when we posed the question, “If you were to know that people who look like you, from wherever your parents are, family may be from, would you be motivated to take part in that research?” And the biggest yes came on the back of that question. And that speaks to the fact that, “If I know that my family or my community, not just in the UK but abroad can benefit, then that would really motivate me and build trust that actually you’re not just here to benefit me as an individual, but you’re here to benefit my community as a whole, and therefore, yes, I’m going to be more trusting of this programme and be more motivated to take part.” 

Naimah: I just wanted to go briefly back, Moestak, you mentioned cultural norms, and I wanted to talk about the cultural norm in societies where maybe people may marry someone from the same ancestor, and what the societal fallout from these practices might be. 

Moestak: The stigma and the stereotypes often for communities comes from those beliefs and messages that are often sometimes not even backed up with scientific evidence. It can be seen as Islamophobic sometimes of Muslim communities that practice that. But also I think what’s important to understand is that concept around hereditary conditions and how that can determine one’s health, and it’s not really fully appreciated or desired. And so as a result, for example, a lot of people refuse to even have those early onset maternal testing for the foetus. My personal experience, I have three children, teenagers now, and I refused those tests as well, because my belief and my religious beliefs would kind of not align with being able to terminate a foetus if there were some genetic conditions. And so I think that is often not understood and made very clear to communities, and build on their beliefs and attitudes and values. And so those are the kind of cultural norms that are not fully understood. 

But also the opposite side of that actually around being able to prevent a good life for somebody or a bad life for somebody, and being able to prevent genetic conditions is also part of the religion on the flipside, but again it’s not creating that link. That cultural beliefs is not understood. I think also the community implications around the stigma. I mean, autism’s a big issue in the Samali community, and I remember years ago when I was working in education, we had a big issue around even acknowledgement of diagnosis and referrals, and it’s because of the stigma. Those perceptions do exist within communities that if someone has a genetic condition or ill health or a disease, it’s almost like being a black sheep in the community. And so it’s being able to build on those desires of the community wanting to be healthy and well, I think is not often understood. 

Naimah: And do you think it’s partly as well education of healthcare professionals to communicate in a really culturally sensitive way? 

Moestak: Yes, exactly, that’s exactly what it is. It’s missed opportunities really that we can build on. In that particular example of autism within the community, I was able to do a really positive piece of work with the community, and building on their interest and their skills, but using my own lived experience and understanding and knowledge, and being able to inform that within education sector but also the health sector, and providing that training and upskilling. And there is unfortunately a lack of diversity within the workforce if you look at the NHS. The lower level kind of cleaning and porter staff are ethnic minorities. And so it is about using those clinicians, as I mentioned earlier, that are coming from those communities are the forefront. 

We’ve recently had a really positive piece of work in Bristol around let’s talk about MMR, and we had a cohort of unvaccinated community, a Somali community, young people between the age of 16 to 25, and we worked with a Somali clinician, who led on that piece of work, and it was absolutely amazing. The young people as a result trusted her information and took up – but again also another thing that’s important is that a lot of data in the medical system is missing. I for one migrated here from the Netherlands, where I came there as a refugee at the age of three years old. My medical history is completely missing in both the UK records but also in the Netherlands, so I didn’t know if I had MMR vaccine. So, it’s a lot of gaps in information that people have, newly arrived communities that still need to constantly be updated and informed and education awareness raised with those communities. 

Naimah: Anna, I wonder if you wanted to add anything onto that point. 

Anna: It’s really difficult with that mistrust and sort of how closed the GRT community is to getting that information in, and I think to getting that information understood as well and to make it seem like it’s important. Because family is the most important thing, people are accepted the way that they are. You know, if we’re talking about autism, people are accepted the way that they are, and it is a bit like, you know, “There’s nothing wrong with my child, how dare you suggest that there is?” That testing isn’t done because the access to healthcare is so difficult, because people can’t register with GPs, because they can’t access maternity care, they can’t access postnatal care. Because they can’t register with the GP, they’re not on the system, and then the records don’t exist. Still now there’s birth records and death records that do not exist for these people within the communities, never mind medical history throughout their lives. 

Naimah: I think it really highlights a lot of gaps, doesn’t it? Aman, do you want to add anything to that question? 

Anna: Your opening remarks is that it’s a cultural norm in all societies, and we see even within the royal family in the UK, that it seems to be that any disparaging comments are targeted towards certain communities, and even then unfairly. I mean, often it’s associated with Muslim communities, but I would say the majority of Muslim communities don’t practice marrying someone from within the same ancestor. It’s certain cultural communities who do practice this. Having said that, even that practice shouldn’t be seen in a disparaging way, because it’s how those communities live their lives, and so we should be respectful of that and not speak in any way disparaging towards that community. And I think we have responsibility – ‘cos obviously nationally the conversation then moves onto increased risks of genetic disorders, and so we should be very matter of fact about what the percentage increase is when it comes to the likelihood of genetic disorders within families who marry with the same ancestor.  

Because what happens is, if we’re not very clear with what the actual facts are with regards to the increased risk of genetic order then even within the community which practices marrying someone from the same ancestor, that figure can be inflated, and so this perpetuates fear and perpetuates the stigma even more. Whereas if we are just matter of fact, “This is the increased risk of genetic disorders,” and leave it there, then the communities can decide and they’ll have a more informed position. I think the figures are an increase from two to six percent increase, but if you were to ask people within the community, “What’s the increase of genetic disorders if you’re marrying someone from the same ancestor?” they might think it’s 40 percent or 50 percent or a really high figure. So, that’s something that we need to work towards better understanding, which will lead to removal of that stigma as well. 

Anna: Again, that’s something that we see in the GRT community as well, there’s been research done by a woman called Sally Anne Lynch into cousin marriage within the Irish travelling community, and when they tested people, they found more than 90 genetic conditions that are present within people’s DNA within that community that just aren’t tested at birth. And I think, you know, you’re right, it’s something that is not talked about, because outside of these communities it’s seen as wrong and it’s not seen as something that’s normal. It’s seen as abnormal. But within this community, it is very normal and it’s very accepted. But then the testing isn’t done because of the access to healthcare. 

Naimah: I think it just seems like it does kind of boil down to education and educating healthcare professionals that it is kind of normal practices. Aman, did you want to add something else? 

Aman: Yeah, Anna made a really good point about testing. I think there’s something that is a gap in the service that we probably don’t provide more widely is that, when it comes to people who practice marriage within the same ancestor in other countries, testing is very normal. So, I know there’s many countries around the world where it’s very standard practice and even a requirement in certain countries that you must be tested before you get married, and so maybe that’s something that we can learn from in the UK. 

Moestak: I think it’s important to understand that some communities, decision making of consent is sometimes done by the head of the family, and I think that that is not fully understood as well, and often can be a barrier to participation. And I think that there’s an element of empowerness that is needed, particularly around women that need that empowerment model around consent of decision making around their testing and genetic testing, and just medical consent. 

Naimah: That’s an excellent point as well, thanks Moestak. 

So, I know we’ve touched on aspects of this already, but I wanted to finish on this question, how can meaningful community engagement foster trust and collaboration in genomic research and healthcare initiatives? 

Aman: I think one of the things that I would really improve is just awareness around genomic healthcare and genomics in general. It’s a learning curve that’s going to happen within communities at different rates, and we need to be mindful of this because that rate will determine also health inequities that are experienced by those communities as well. So, we need to make sure that we are adequately approaching all communities to the best of our abilities. Having said that, target maybe more resourcing and educational opportunities for communities which have been underrepresented in health research and in genomic health research as well primarily, so we need to sort of prioritise certain communities in regards to our community outreach, because then we’ll dispel any myths that people might have and work towards chipping away at the mistrust that certain communities may feel towards just healthcare in general, but more particularly about genomic healthcare, ‘cos genomic healthcare brings up some unique challenges and some unique perspectives within communities. 

So, there’s a number of fears about the future, but also misgivings about healthcare in the past as well that we need to acknowledge. So, by having community engagement initiatives, which are prioritised from the beginning and not just an afterthought, we can go a long way towards getting over some of the challenges of the past, but also not making new challenges for us in the future.  

Anna: I think as a whole, the UK has got a long way to go with building trust with the GRT community. I think it’s going to take some time. They still are one of the most marginalised communities. For example, in the area that I live, there was a GRT funeral going on a few weeks ago, and all the pub shut because they didn’t want GRT communities in their establishments, and there is no other community or minority that that would happen with now. So, I think there is still quite a long way to go to gain the trust of the GRT community. And in terms of healthcare, I think we need to go right back to the start and learn about these communities, and understand their cultures and their practices, and how they work without that judgement. Living a nomadic lifestyle is still criminalised. There needs to be a decriminalisation around these communities before we can even start to begin to work out how to go there and allow them to access healthcare and knowledge and information around genetic conditions, and around health and mental health.  

It’s going to be a very long road from here, but I think what we can start doing is to start that destigmatisation. If you are a doctor and somebody turns up in your surgery identifying as someone from the GRT community, understanding the background they come from, and not having all those prejudices, you know, which is very difficult to do, to get rid of those thoughts that you already have about someone. I think we need to make a real effort to start, and I think there needs to be changes within the NHS in order for people to access healthcare better. I think the resources that are given and the information that goes out needs to be more specifically tailored to these communities if that’s who you’re trying to engage with, because there’s so much that goes on in the community that’s not known outside of the community, and it’s not spoken about, and within different GRT communities as well. You know, there are different GRT communities all around the UK, and what goes on in them is not known to other GRT communities either.  

So, it’s about being specific with the information that you’re getting out, with who you’re actually targeting. And I think a bit like we were saying earlier, it’s the women, you know. The women have childcare responsibilities almost all of the time, and they are the ones who bring up the children, but they’re not necessarily the ones that make the decisions about the children or the child healthcare. You know, women are expected to do jobs in the morning. Women are not available before 11 o’clock in the morning. So, think about when you’re making appointments for. Think about when you’re going. I think it is going to be a long, long road before we get there, you know, with building trust and getting the information out there, but I think we can make a start. 

Naimah: Yeah, it does seem like there is lots of ways we can start tackling it slowly. Moestak, I wonder if you had anything you wanted to add. 

Moestak: As a public health specialist, you know, we’ve not been taught genomic medicine or genomic health at all in terms of how that can benefit and radically change the NHS and improve determinants of health, so that’s a massive gap of knowledge within the healthcare sector and professionals. But I think in terms of addressing the historic mistrust, I think there needs to be an acknowledgement and a real openness around the historic, you know, abuse and unethical practices that have existed within health. There are other countries that are much more advanced in that and really embedding that within communities through pledges. That long-term kind of piece of work for me is missing. You know, it’s that wider education piece that’s missing that needs to be really embedded in the culture. 

But I think also investing in the infrastructure in the community. Like far too often, if the long-term vision is not there, communities are reluctant to get involved and have trust within that, so I think that’s an important part as well. And I think it’s also about demonstrating the benefits of genomic medicine. I think that needs to be done in a community level way, through storytelling. I know that there’s now a lot of development around cancer treatments around genomics, but I think it’s about having those people who have those lived experiences from different communities to be able to share the benefits and demonstrate that through their way, and being appropriately reimbursed as well. I think that’s really important. 

I think generally, I think there’s a long way we’ve got to go. I’ll never forget when I went to Vancouver on a conference around health, and there was a lot of reconciliation there, where there was really acknowledgement, and the indigenous communities there that have a lot of health disparities were able to kind of overcome some of that and start building as a community and addressing tackling health inequalities because that trust was built and that acknowledgement from high up, from government level, all the way trickled down to local. I think also patient centred approaches around – like we mentioned, we talked about linking the cultural norms and the values and the beliefs that people have, and the skills and the assets that they have to be able to lead on these solutions themselves, that really needs to be embedded to build trust.  

Aman touched on the perception around what could be done with genomic data. I don’t know if Aman wants to elaborate a bit on that, but that’s really important. It’s a big barrier. It’s how do we create transparent ways of storing data, but also use various ways of communication. It doesn’t have to be traditional reports. It could be through podcasts. It could be like community messaging.  

Naimah: Yeah, I think that’s a really important point. Aman, did you want to come in on that? 

Aman: Yeah, I think sharing the stories of the past in an appropriate setting, in an appropriate manner as well – ‘cos it’s a bit of a double edged sword, ‘cos you don’t want to scare people who are unfamiliar with these stories, but at the same time there’s a moral responsibility for all of us involved in this space to speak about these issues, one from the perspective of acknowledging what’s happened in the past, so then people feel like, “Okay, you’re not trying to hide anything here,” but from the perspective of also that we need to make sure that we don’t repeat some of the mistakes in the future, and that as people involved in genomic healthcare and involved in this space, that we’re cognisant of these misgivings in the past, and we’re cognisant of our responsibility to safeguard communities in the future. 

Naimah: Okay, so we’re going to wrap up there. Thank you so much to our guests, Anna Smith, Aman Ali and Moestak Hussein for joining me today as we discussed the barriers to access to genomic medicine for diverse communities, and the impact it has on these communities. If you’d like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. I’ve been your host and producer, Naimah Callachand, and this podcast was edited by Bill Griffin at Ventoux Digital.

Pharmacogenomics plays a critical role in personalised medicine, as some adverse drug reactions are genetically determined. Adverse drugs reactions (ADRs) account for 6.5% of hospital admissions in the UK, and the application of pharmacogenomics to look at an individuals response to drugs can significantly enhance patient outcomes and safety.

In this episode, our guests discuss how genomic testing can identify patients who will respond to medications and those who may have adverse reactions. We hear more about Genomics England's collaboration with the Medicines and Healthcare products Regulatory Agency in the Yellow Card Biobank and our guests discuss the challenges of implementing pharmacogenomics into the healthcare system.

Our host Vivienne Parry, Head of Public Engagement at Genomics England, is joined by Anita Hanson, Research Matron and the Lead Research Nurse for clinical pharmacology at Liverpool University Hospitals NHS Foundation Trust, and Professor Bill Newman, Professor of translational genomic medicine at the Manchester Center for Genomic Medicine, and Professor Matt Brown, Chief Scientific Officer at Genomics England.

"I think we’re moving to a place where, rather than just doing that one test that might be relevant to one drug, we’d be able to do a test which at the same price would generate information that could be relevant at further points in your life if you were requiring different types of medicine. So, that information would then be available in your hospital record, in your GP record, that you could have access to it yourself. And then I think ultimately what we would really love to get to a point is where everybody across the whole population just has that information to hand when it’s required, so that they’re not waiting for the results of a genetic test, it’s immediately within their healthcare record."

You can watch this video learn more about Jane's lived experience with Stevens-Johnson syndrome, on The Academy of Medical Sciences' (AMS) YouTube channel. The story, co-produced by Areeba Hanif from AMS, provides an in-depth look at Jane's journey.

Want to learn more about personalised medicine? Listen to our Genomics 101 episode where Professor Matt Brown explains what it is in less than 5 minutes: Genomics 101: What is personalised medicine? 

You can download the transcript or read it below.

Vivienne: Hello and welcome to Behind the Genes. 

Bill: What we’ve seen is that the limited adoption so far in the UK and other countries has focused particularly on severe adverse drug reactions. They’ve been easier to identify and there’s a clear relationship between some drugs and some genetic changes where that information is useful. So, a good example has been the recent adoption of pharmacogenetic testing for a gene called DPYD for patients undergoing cancer treatment, particularly breast and bowel cancer. And if you have an absence of the enzyme that that gene makes, if you’re given that treatment, then you can end up on intensive care and die, so it’s a really significant side effect. But as you say, the most common side effects aren’t necessarily fatal, but they can have a huge impact upon people and on their wellbeing. 

Vivienne: My name’s Vivienne Parry and I’m head of public engagement at Genomics England, and today we’ll be discussing the critical role of pharmacogenomics in personalised medicine, highlighting its impact on how well medicines work, their safety, and on patient care. I’m joined today by Professor Bill Newman, professor of translational genomic medicine at the Manchester Centre for Genomic Medicine, Anita Hanson, research matron, a fabulous title, and lead research nurse for clinical pharmacology at the Liverpool University Hospital’s NHS Foundation Trust, and Professor Matt Brown, chief scientific officer for Genomics England. And just remember, if you enjoy today’s episode, we’d love your support, so please like, share and rate us on wherever you listen to your podcasts. 

So, first question to you, Bill, what is pharmacogenomics? 

Bill: Thanks Viv. I think there are lots of different definitions, but how I think of pharmacogenetics is by using genetic information to inform how we prescribe drugs, so that they can be safer and more effective. And we’re talking about genetic changes that are passed down through families, so these are changes that are found in lots of individuals. We all carry changes in our genes that are important in how we transform and metabolise medicines, and how our bodies respond to them. 

Vivienne: Now, you said pharmacogenetics. Is it one of those medicine things like tomato, tomato, or is there a real difference between pharmacogenetics and pharmacogenomics? 

Bill: So, people, as you can imagine, do get quite irate about this sort of thing, and there are lots of people that would contest that there is a really big important difference. I suppose that pharmacogenetics is more when you’re looking at single changes in a relatively small number of genes, whereas pharmacogenomics is a broader definition, which can involve looking at the whole genome, lots of genes, and also whether those genes are switched on or switched off, so the expression levels of those genes as well would encompass pharmacogenomics. But ultimately it’s using genetic information to make drug prescription safer and more effective. 

Vivienne: So, we’re going to call it pharmacogenomics and we’re talking about everything, that’s it, we’ll go for it. So Matt, just explain if you would the link between pharmacogenomics and personalised medicine. And I know that you’ve done a big Genomics 101 episode about personalised medicine, but just very briefly, what’s the link between the two? 

Matt: So, personalised medicine’s about using the right dose of the right drug for the right individual. And so pharmacogenomics helps you with not only ensuring that you give a medication which doesn’t cause problems for the person who receives it, so an adverse drug reaction, but also that they’re actually getting the right dose. Of course, people’s ability to metabolise, activate and respond to drugs genetically is often genetically determined, and so sometimes you need to adjust the dose up or down according to a person’s genetic background. 

Vivienne: Now, one of the things that we’ve become very aware of is adverse drug reactions, and I think they account for something like six and a half percent of all hospital admissions in the UK, so it’s absolutely huge. Is that genetically determined adverse drug reactions? 

Matt: So, the answer to that is we believe so. There’s quite a bit of data to show that you can reduce the risk of people needing a hospital admission by screening genetic markers, and a lot of the very severe reactions that lead to people being admitted to hospital are very strongly genetically determined. So for example, there are HLA types that affect the risk of adverse drug reactions to commonly used medications for gout, for epilepsy, some HIV medications and so on, where in many health services around the world, including in England, there are already tests available to help prevent those leading to severe reactions. It’s likely though that actually the tests we have available only represent a small fraction of the total preventable adverse drug reactions were we to have a formal pre-emptive pharmacogenomics screening programme. 

Vivienne: Now, I should say that not all adverse drug reactions are genetic in origin. I mean, I remember a rather nasty incident on the night when I got my exam results for my finals, and I’d actually had a big bee sting and I’d been prescribed antihistamines, and I went out and I drank rather a lot to celebrate, and oh my goodness me, I was rather ill [laughter]. So, you know, not all adverse drug reactions are genetic in origin. There are other things that interact as well, just to make that clear to people. 

Matt: Yes, I think that’s more an interaction than an adverse drug reaction. In fact frankly, the most common adverse drug reaction in hospitals is probably through excess amounts of water, and that’s not medically determined, that’s the prescription. 

Vivienne: Let me now come to Anita. So, you talk to patients all the time about pharmacogenomics in your role. You’ve been very much involved in patient and public involvement groups at the Wolfson Centre for Personalised Medicine in Liverpool. What do patients think about pharmacogenomics? Is it something they welcome? 

Anita: I think they do welcome pharmacogenomics, especially so with some of the patients who’ve experienced some of the more serious, life threatening reactions. And so one of our patients has been doing some work with the Academy of Medical Sciences, and she presented to the Sir Colin Dollery lecture in 2022, and she shared her story of having an adverse drug reaction and the importance of pharmacogenomics, and the impact that pharmacogenomics can have on patient care. 

Vivienne: Now, I think that was Stevens-Johnson syndrome. We’re going to hear in a moment from somebody who did experience Stevens-Johnson’s, but just tell us briefly what that is. 

Anita: Stevens-Johnson syndrome is a potentially life threatening reaction that can be caused by a viral infection, but is more commonly caused by a medicine. There are certain groups of medicines that can cause this reaction, such as antibiotics or anticonvulsants, nonsteroidal anti-inflammatories, and also a drug called allopurinol, which is used to treat gout. Patients have really serious side effects to this condition, and they’re often left with long-term health complications. The morbidity and mortality is considerable as well, and patients often spend a lot of time in hospital and take a long time to recover.  

Vivienne: And let’s now hear from Jane Burns for someone with lived experience of that Stevens-Johnson syndrome. When Jane Burns was 19, the medicine she took for her epilepsy was changed. 

Jane: I remember waking up and feeling really hot, and I was hallucinating, so I was taken to the Royal Liverpool Hospital emergency department by my parents. When I reached A&E, I had a temperature of 40 degrees Celsius. I was given Piriton and paracetamol, and the dermatologist was contacted. My mum had taken my medication to hospital and explained the changeover process with my epilepsy medication. A decision was made to discontinue the Tegretol and I was kept in for observation. Quite rapidly, the rash was changing. Blisters were forming all over my body, my mouth was sore and my jaw ached. My temperature remained very high. It was at this point that Stevens-Johnson syndrome, or SJS, was diagnosed. 

Over the next few days, my condition deteriorated rapidly. The rash became deeper in colour. Some of the blisters had burst, but some got larger. I developed ulcers on my mouth and it was extremely painful. I started to lose my hair and my fingernails. As I had now lost 65 percent of my skin, a diagnosis of toxic epidermal necrolysis, or TEN, was made. Survivors of SJS TEN often suffer with long-term visible physical complications, but it is important to also be aware of the psychological effects, with some patients experiencing post-traumatic stress disorder. It’s only as I get older that I realise how extremely lucky I am to have survived. Due to medical and nursing expertise, and the research being conducted at the time, my SJS was diagnosed quickly and the medication stopped. This undoubtedly saved my life. 

Vivienne: Now, you’ve been looking at the development of a passport in collaborating with the AMS and the MHRA. Tell me a bit more about that. 

Anita: Yes, we set up a patient group at the Wolfson Centre for Personalised Medicine approximately 12 years ago, and Professor Sir Munir Pirmohamed and I, we wanted to explore a little bit more about what was important to patients, really to complement all the scientific and clinical research activity within pharmacogenomics. And patients recognised that, alongside the pharmacogenomic testing, they recognised healthcare professionals didn’t really have an awareness of such serious reactions like Stevens-Johnson syndrome, and so they said they would benefit from having a My SJS Passport, which is a booklet that can summarise all of the important information about their care post-discharge, and this can then be used to coordinate and manage their long-term healthcare problems post-discharge and beyond. And so this was designed by survivors for survivors, and it was then evaluated as part of my PhD, and the findings from the work suggest that the passport is like the patient’s voice, and it really does kind of validate their diagnosis and raises awareness of SJS amongst healthcare professionals. So, really excellent findings from the research, and the patients think it's a wonderful benefit to them. 

Vivienne: So, it’s a bit like a kind of paper version of the bracelet that you sometimes see people wearing that are on steroids, for instance. 

Anita: It is like that, and it’s wonderful because it’s a handheld source of valuable information that they can share with healthcare professionals. And this is particularly important if they’re admitted in an emergency and they can’t speak for themselves. And so the passport has all that valuable information, so that patients aren’t prescribed that drug again, so it prevents them experiencing a serious adverse drug reaction again.  

Vivienne: So, Stevens-Johnson, Bill, is a really scary side effect, but what about the day to day benefits of pharmacogenomics for patients? 

Bill: So, what we’ve seen is that the limited adoption so far in the UK and other countries has focused particularly on severe adverse drug reactions. They’ve been easier to identify and there’s a clear relationship between some drugs and some genetic changes where that information is useful. So a good example has been the recent adoption of pharmacogenetic testing for a gene called DPYD for patients undergoing cancer treatment, particularly breast and bowel cancer. And if you have an absence of the enzyme that that gene makes, if you’re given that treatment, then you can end up on intensive care and die, so it’s a really significant side effect. But as you say, the most common side effects aren’t necessarily fatal, but they can have a huge impact upon people and on their wellbeing.  

And it’s not just in terms of side effects. It’s in terms of the effectiveness of the medicine. Because if a person is prescribed a medicine that doesn’t or isn’t going to work for them then it can take them longer to recover, to get onto the right medicine. That can have all sorts of detrimental effects. And so when we’re thinking about introducing pharmacogenetics more broadly rather than just on a single drug or a single gene basis, we’re thinking about that for common drugs like antidepressants, painkillers, statins, the drugs that GPs are often prescribing on a regular basis to a whole range of patients. 

Vivienne: So, to go back to you, Anita, we’re really talking about dose here, aren’t we, whether you need twice the dose or half the dose depending on how quickly your body metabolises that particular medicine. How do patients view that? 

Anita: Well, the patient in question who presented for the Academy of Medical Sciences, I mean, her take on this was, she thinks pharmacogenetics is wonderful because it will allow doctors and nurses to then prescribe the right drug, but also to adapt the dose accordingly to make sure that they get the best outcome, which provides the maximum benefit while also minimising any potential harm. And so from her perspective, that was one of the real benefits of pharmacogenomics. But she also highlighted about the benefits for future generations, the fear of her son taking the same medicine and experiencing the same reaction. And so I think her concerns were, if we have pharmacogenetic testing for a panel of medicines, as Bill mentioned then, then perhaps this would be fantastic for our children as they grow up, and we can identify and predict and prevent these type of reactions happening to future generations. 

Vivienne: And some of these drugs, Bill, are really very common indeed, something like codeine. Just tell us about codeine, ‘cos it’s something – whenever I tell this to friends [laughter], they’re always completely entranced by the idea that some people don’t need nearly as much codeine as others. 

Bill: Yeah, so codeine is a drug that’s very commonly used as a painkiller. To have its real effect, it needs to be converted in the body to a different drug called morphine, and that is done by an enzyme which is made by a gene called CYP2D6. And we all carry changes in CYP2D6, and the frequency of those variants, whether they make the gene work too much or whether they make it work too little, they vary enormously across the world, so that if you go to parts of Africa, about 30 percent of the population will make more of the CYP2D6, and so they will convert the codeine much more quickly, whereas if you go to the UK, maybe up to ten percent of the white population in the UK just won’t be converting codeine to morphine at all, so they won’t get any benefit from the drug. So at both ends, you have some people that don’t respond and some people that respond a little bit too much so that they need either an alternative drug or they need a different dose. 

Vivienne: So, all those people who say, you know, “My headache hasn’t been touched by this painkiller,” and we say, “What a wimp you’re being,” actually, it’s to do with genetics. 

Bill: Yeah, absolutely. There’s a biological reason why people don’t – not for everybody, but for a significant number of people, that’s absolutely right, and we can be far more tailored in how we prescribe medication, and get people onto painkillers that work for them much more quickly. 

Vivienne: And that’s so interesting that it varies by where you come from in the world, because that means we need to give particular attention – and I’m thinking, Anita, to working with patients from different community groups, to make sure that they understand the need for pharmacogenomics. 

Anita: I think that’s really important, Vivienne, and I think we are now having discussions with the likes of Canada SJS awareness group, and also people have been in touch with me from South Africa because people have requested the passport now to be used in different countries, because they think it’s a wonderful tool, and it’s about raising awareness of pharmacogenomics and the potential benefits of that, and being able to share the tools that we’ve got to help patients once they’ve experienced a serious reaction. 

Vivienne: So, pharmacogenomics clearly is important in the prevention of adverse drug reactions, better and more accurate prescribing, reduced medicines wastage. Does this mean that it’s also going to save money, Bill, for the NHS? 

Bill: Potentially. It should do if it’s applied properly, but there’s lots of work to make sure that not only are we using the right evidence and using the right types of tests in the laboratory, but we’re getting the information to prescribers, so to GPs, to pharmacists, to hospital doctors, in a way that is understandable and meaningful, such that they can then act upon that information. So, the money will only be saved and then can be reused for healthcare if the whole process and the whole pathway works, and that information is used effectively. 

Vivienne: So, a lot of research to make sure that all of that is in place, and to demonstrate the potential cost savings. 

Bill: Yes. I mean, there are very nice studies that have been done already in parts of the world that have shown that the savings that could be accrued for applying pharmacogenetics across common conditions like depression, like in patients to prevent secondary types of strokes, are enormous. They run into hundreds of millions of pounds or dollars. But there is an initial investment that is required to make sure that we have the testing in place, that we have the digital pathways to move the information in place, and that there’s the education and training, so that health professionals know how to use the information. But the potential is absolutely enormous. 

Vivienne: Matt, can I turn now to the yellow card. So, people will be very familiar with the yellow card system. So, if you have an adverse reaction, you can send a yellow card in – I mean, literally, it is a yellow card [laughter]. It does exactly what it says on the tin. You send a yellow card to the MHRA, and they note if there’s been an adverse effect of a particular medicine. But Genomics England is teaming up with the MHRA to do something more with yellow cards, and we’re also doing this with the Yellow Card Biobank. Tell us a bit more. 

Matt: So, yellow card’s a great scheme that was set up decades ago, initially starting off, as you said, with literally yellow cards, but now actually most submissions actually come online. And it’s important to note that submissions can come not just from healthcare providers, but majority of submissions actually come from patients themselves, and that people should feel free, if they feel they’ve had an adverse drug reaction, to report that themselves rather than necessarily depending on a medical practitioner or the healthcare provider to create that report. So, Genomics England is partnering with the MHRA in building what’s called the Yellow Card Biobank, the goal of which is to identify genetic markers for adverse drug reactions earlier than has occurred in the past, so that we can then introduce genetic tests to prevent these adverse drug reactions much sooner than has occurred previously.  

So, what we’re doing is basically at the moment we’re doing a pilot, but the ultimate plan is that in future, patients who report a serious adverse drug reaction through the Yellow Card Biobank will be asked to provide a sample, a blood sample, that we then screen. We do a whole genome sequence on it, and then combine these with patients who’ve had like adverse drug reactions and identify genetic markers for that adverse drug reaction medication earlier, that can then be introduced into clinical practice earlier. And this should reduce by decades the amount of time between when adverse drug reactions first start occurring with medications and us then being able to translate that into a preventative mechanism. 

Vivienne: And will that scheme discover, do you think, new interactions that you didn’t know about before? Or do you expect it to turn up what you already know about? 

Matt: No, I really think there’s a lot of discovery that is yet to happen here. In particular, even for drugs that we know cause adverse drug reactions, mostly they’ve only been studied in people of European ancestry and often in East Asian ancestry, but in many other ancestries that are really important in the global population and in the UK population, like African ancestry and South Asian ancestries, we have very little data. And even within Africa, which is an area which is genetically diverse as the rest of the world put together, we really don’t know what different ethnicities within Africa, actually what their genetic background is with regard to adverse drug reactions. 

The other thing I’d say is that there are a lot of new medications which have simply not been studied well enough. And lastly, that at the moment people are focused on adverse drug reactions being due to single genetic variants, when we know from the model of most human diseases that most human diseases are actually caused by combinations of genetic variants interacting with one another, so-called common disease type genetics, and that probably is similarly important with regard to pharmacogenomics as it is to overall human diseases. That is, it’s far more common that these are actually due to common variants interacting with one another rather than the rare variants that we’ve been studying to date. 

Vivienne: So, it’s a kind of cocktail effect, if you like. You know, you need lots of genes working together and that will produce a reaction that you may not have expected if you’d looked at a single gene alone. 

Matt: That’s absolutely correct, and there’s an increasing amount of evidence to show that that is the case with medications, but it’s really very early days for research in that field. And the Yellow Card Biobank will be one of many approaches that will discover these genetic variants in years to come. 

Vivienne: Now, Matt’s a research scientist. Bill, you’re on the frontline in the NHS. How quickly can this sort of finding be translated into care for people in the NHS? 

Bill: So, really quickly is the simple answer to that, Viv. If we look at examples from a number of years ago, there’s a drug called azathioprine that Matt has used lots in some of his patients. In rheumatology, it’s used for patients with inflammatory bowel disease. And the first studies that showed that there was a gene that was relevant to having bad reactions to that drug came out in the 1980s, but it wasn’t until well into this century, so probably 30-plus years later that we were routinely using that test in clinical medicine. So, there was an enormous lot of hesitancy about adopting that type of testing, and a bit of uncertainty. If you move forward to work that our colleague Munir Pirmohamed in Liverpool has done with colleagues in Australia like Simon Mallal around HIV medicine, there was this discovery that a drug called abacavir, that if you carried a particular genetic change, that you had a much higher risk of having a really severe reaction to that. The adoption from the initial discovery to routine, worldwide testing happened within four years.  

So, already we’ve seen a significant change in the appetite to move quickly to adopt this type of testing, and I see certainly within the NHS and within other health systems around the world, a real desire to adopt pharmacogenetics into routine clinical practice quickly and at scale, but also as part of a broader package of care, which doesn’t just solely focus on genetics, but thinks about all the other parts that are important in how we respond to medication. So, making sure we’re not on unusual combinations of drugs, or that we’re taking our medicine at the right time and with food or not with food, and all of those other things that are really important. And if you link that to the pharmacogenetics, we’re going to have a much safer, more effective medicines world. 

Vivienne: I think one of the joys of working at Genomics England is that you see some of this work really going into clinical practice very fast indeed. And I should say actually that the Wolfson Centre for Personalised Medicine, the PPI group that Anita looks after so well, they’ve been very important in recruiting people to Yellow Card Biobank. And if anyone’s listening to this, Matt, and wants to be part of this, how do they get involved? Or is it simply through the yellow card? 

Matt: So at the moment, the Yellow Card Biobank is focusing on alopurinol.  

Vivienne: So, that’s a medicine you take for gout. 

Matt: Which I use a lot in my rheumatology clinical practice. And direct acting oral anticoagulants, DOACs, which are used for vascular disease therapies and haemorrhage as a result of that. So, the contact details are available through the MHRA website, but I think more importantly, it’s just that people be aware of the yellow card system itself, and that if they do experience adverse drug reactions, that they do actually complete a report form, ‘cos I think still actually a lot of adverse drug reactions go unreported. 

Vivienne: I’m forgetting of course that we see Matt all the time in the Genomics England office and we don’t think that he has any other home [laughter] than Genomics England, but of course he still sees some patients in rheumatology clinic. So, I want to now look to the future. I mean, I’m, as you both know, a huge enthusiast for pharmacogenomics, ‘cos it’s the thing that actually, when you talk to patients or just the general public, they just get it straight away. They can’t think why, if you knew about pharmacogenomics, why you wouldn’t want to do it. But it’s not necessarily an easy thing to do. How can we move in the future, Bill, to a more proactive approach for pharmacogenomics testing? Where would we start? 

Bill: Yes, so I think we’ve built up really good confidence that pharmacogenetics is a good thing to be doing. Currently, we’re doing that predominantly at the point when a patient needs a particular medicine. That’s the time that you would think about doing a genetic test. And previously, that genetic test would only be relevant for that specific drug. I think we’re moving to a place where, rather than just doing that one test that might be relevant to one drug, we’d be able to do a test which at the same price would generate information that could be relevant at further points in your life if you were requiring different types of medicine. So, that information would then be available in your hospital record, in your GP record, that you could have access to it yourself. And then I think ultimately what we would really love to get to a point is where everybody across the whole population just has that information to hand when it’s required, so that they’re not waiting for the results of a genetic test, it’s immediately within their healthcare record. That’s what we’d call pre-emptive pharmacogenetic testing, and I think that’s the golden land that we want to reach. 

Vivienne: So for instance, I might have it on my NHS app, and when I go to a doctor and they prescribe something, I show my app to the GP, or something pops up on the GP’s screen, or maybe it’s something that pops up on the pharmacist’s screen. 

Bill: I think that’s right. I think that’s what we’re looking to get to that point. We know that colleagues in the Netherlands have made some great progress at developing pathways around that. There’s a lot of public support for that. And pharmacists are very engaged in that. In the UK, the pharmacists, over the last few years, have really taken a very active role to really push forward this area of medicine, and this should be seen as something that is relevant to all people, and all health professionals should be engaged with it. 

Vivienne: And on a scale of one to ten, how difficult is it going to be to implement in the NHS? 

Bill: So, that’s a difficult question. I think the first thing is identifying what the challenges are. So I have not given you a number, I’ve turned into a politician, not answered the question. So, I think what has happened over the last few years, and some of our work within the NHS Network of Excellence in pharmacogenetics and some of the other programmes of work that have been going on, is a really good, honest look at what it is we need to do to try to achieve pharmacogenetics implementation and routine use. I don’t think the challenge is going to be predominantly in the laboratory. I think we’ve got phenomenal laboratories. I think we’ve got great people doing great genetic testing. I think the biggest challenges are going to be about how you present the data, and that data is accessible. And then ensuring that health professionals really feel that this is information that isn’t getting in the way of their clinical practice, but really making a difference and enhancing it, and of benefit both to the healthcare system but more importantly to the patients. 

Vivienne: Now, when I hear you both talk, my mind turns to drug discovery and research, and Matt, I’m quite sure that that’s right at the top of your mind. Tell us how pharmacogenomics can help in drug discovery and research. 

Matt: So, pharmacogenomics, I think actually just genetic profiling of diseases in itself just to start off with is actually a really good way of identifying new potential therapeutic targets, and also from derisking drug development programmes by highlighting likely adverse drug reactions of medications that are being considered for therapeutic trials, or targets that are being considered for therapeutic development. Pharmacogenomics beyond that is actually largely about – well, it enables drug development programmes by enabling you to target people who are more likely to respond, and avoid people who are more likely to have adverse drug reactions. And so that therapeutic index of the balance between likely efficacy versus likely toxicity, genetics can really play into that and enable medications to be used where otherwise they might have failed. 

This is most apparent I think in the cancer world. A classic example there, for example, is the development of a class of medications called EGFR inhibitors, which were developed for lung cancer, and in the initial cancer trials, actually were demonstrated to be ineffective, until people trialled them in East Asia and found that they were effective, and that that turns out to be because the type of cancers that respond to them are those that have mutations in the EGFR gene, and that that’s common in East Asians. We now know that, wherever you are in the world, whether you’re East Asian or European or whatever, if you have a lung adenocarcinoma with an EGFR mutation, you’re very likely to respond to these medications. And so that pharmacogenomic discovery basically rescued a class of medication which is now probably the most widely used medication for lung adenocarcinomas, so a huge beneficial effect. And that example is repeated across multiple different cancer types, cancer medication types, and I’m sure in other fields we’ll see that with expansive new medications coming in for molecularly targeted therapies in particular. 

Vivienne: So, smaller and more effective trials rather than larger trials that perhaps seem not to work but actually haven’t been tailored enough to the patients that are most likely to benefit. 

Matt: Yeah, well, particularly now that drug development programmes tend to be very targeted at specific genetic targets, pharmacogenetics is much more likely to play a role in identifying patients who are going to respond to those medications. So, I think many people in the drug development world would like to see that, for any significant drug development programme, there’s a proper associated pharmacogenomic programme to come up with molecular markers predicting a response. 

Vivienne: We’re going to wrap up there. Thank you so much to our guests, Bill Newman, Anita Hanson, Matt Brown, and our patient Jane Burns. Thank you so much for joining us today to discuss pharmacogenomics in personalised medicine, and the benefits, the challenges and the future prospects for integrating pharmacogenomics into healthcare systems. And if you’d like to hear more podcasts like this, please subscribe to Behind the Genes. It’s on your favourite podcast app. Thank you so much for listening. I’ve been your host, Vivienne Parry. This podcast was edited by Bill Griffin at Ventoux Digital and produced by the wonderful Naimah. Bye for now.