Behind the Genes

In this explainer episode, Dr Jude Hayward, GP and Principal Clinician for Primary Care at Genomics England, explains what we mean by pharmacogenomics.

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, let us know on podcast@genomicsengland.co.uk.

You can download the transcript or read it below.

Florence: [00:00:00] What do we mean by pharmacogenomics? My name is Florence Cornish, and today I'm here with Jude Hayward, who is principal clinician for primary care here at Genomics England, and she is going to be telling us much more about the topic.

So, Jude, thanks so much for being here. It's great to have you.

Jude: Thank you, Florence, and thank you for the invitation, delighted to be here. I'm Dr. Jude Hayward. I am principal clinician for primary care, and that's my role within Genomics England. I am a GP, and I work half-time as a GP, and I also work as a GPER, a GP with an extended role in clinical genetics. I have other roles nationally, working as primary care lead for the Genomics Education Programme, and also representing genomic medicine for the Royal College of General Practitioners.

And really, this is through my interest in implementing genomic medicine into primary care, supporting my primary care colleagues, and this most recently has led me to have an interest in pharmacogenomics.

Florence: [00:01:00] And so, Jude, when we say the word pharmacogenomics, we're actually saying a combination of two words, right? We're saying pharmacology, combined with genomics.

And so, it might be helpful if we could start by explaining each of those on their own first. Could you talk through what we mean by the word genomics?

Jude: Yes, absolutely. And genomics will be familiar to the listeners of the podcast. The genome is our full set of DNA. Part of the genome is genes, and each of these genes acts as an instruction, so the genome acts as an instruction manual for everything about us. Genomics is the study of this genome, and genomic medicine is how the genome can impact their health.

Florence: Mm-hmm.

Jude: Moving on to pharmacology, this is the study of how medicines and chemicals interact with and affect the body and how we process and handle medications within our bodies.

Florence: And so if we combine both of these together, genomics and pharmacology, we get this pharmacogenomics, which is presumably kind of a mashup of the two, right? Looking at how a person's genes can affect their response to medicines.

[00:02:00] Would you say that that's accurate? Can you tell us a little bit more about it?

Jude: Yes. I think that's a great description, Florence. So yes, essentially, pharmacogenomics is a study of how a person's genome interacts with the way that they respond to medication. So, it is a type of personalized medication. We all carry the same genes. We all carry the genes which affect the way that we respond to medications, and we carry changes or variants in these genes which affect the way that we handle certain medications.

[00:02:30] But these only become relevant if we are prescribed a medication which is going to interact and form what's called a gene-drug pair.

Florence: Yeah. So, tell me a little bit more about that. Why do medicines work differently for different people? Why do we see this happening?

Jude: Well, there's a variety of different reasons for this. There's multiple factors which affect how an individual may respond or react to a certain medication. So pharmacogenomics is one, and even there, there are multiple different variants that may occur. And so there are multiple different ways in which our genomic information, our genomes, can affect how we respond.

[00:03:00] But in addition to that, there's all sorts of other things as well. So, what we eat affects how we might react to medication. Other genes, maybe other conditions that we have will affect how we react to a medication, other medications we're taking will affect how we react to a medication and there's all sorts of other environmental factors as well.

Florence: Do you have any real-world examples that we know of, of genes that people have that might affect their response to specific medications?

Jude: [00:03:30] Yes. The one that I'm going to talk about is one called CYP2C19. Now, that's how it's said, but it's actually spelt C-Y-P-2-C-1-9, which is just essentially a reference number for the gene CYP2C19.

This is one that people may have heard of because it's been in the news over the last couple of years. So, we know that if people have a stroke or a mini stroke, that at the moment the usual practice is to offer them a prescription of a medication that can thin their blood down, and one of the common ones is one called clopidogrel.

Florence: [00:04:00] Mm-hmm.

Jude: And this has been prescribed for people for many, many years, and it can help reduce the chances of them having a second stroke or a second TIA. However, certain variants in the CYP2C19 gene can affect the way that people process clopidogrel in the body. And there are some groups of people, and I can go on to discuss this in more detail, but there are some groups of people in whom it is less effective.

[00:04:30] And therefore, if we test the CYP2C19 gene, it can give us information as to whether somebody should be given a standard dose of clopidogrel or whether it's less likely to be effective for them, in which case they may be recommended an alternative medication or even a different dose of clopidogrel.

Florence: You mentioned earlier something called a gene-drug pair. That's a term I've actually never heard before. Could you tell me a little bit more about what that is?

Jude: So a gene-drug pair is formed when somebody has a variant in a relevant gene and they are prescribed a medication, and the medication prescribed is affected by the variant that they have in that gene.

Florence: [00:05:00] Right.

Jude: So in that instance, a gene-drug pair is formed. There's two main ways that it may be important. It may be that it means that somebody is more or less likely to develop a side effect to that medication, or it may give us information that the medication is going to be more or less effective in them.

Florence: Right.

Jude: It can never tell us in a black-and-white way that somebody will or won't have a reaction or if they will or won't benefit from the medication, but it helps us predict who's more likely to have a side effect and who is more likely to benefit.

Florence: And so, tell me about how a specific genetic variant can mean that a drug is less or more effective in that individual.

Jude: So, I'm going to carry on with the example of CYP2C19 that we've been talking about. The CYP2C19 gene codes a protein, which is an enzyme, which processes certain medications in the body.

[00:06:00] So variants affect the level of function of this enzyme. So certain variants mean that the enzyme works much more quickly and therefore processes or metabolizes medications much more quickly.

And if that happens, people are termed rapid metabolizers or ultra-rapid metabolizers because of the speed that they're metabolizing. Conversely, other variants in the CYP2C19 gene can reduce the function of that enzyme, which then means that people metabolize or process medications more slowly and then tend to be called poor metabolizers.

So people who are poor metabolizers of clopidogrel, they don't process clopidogrel to the active medication in the body, and so there is less available of the active medication in the body and therefore that means that it's less effective for them.

Florence: Right. And all of that information will affect the amount that they're prescribed or the drug that they're prescribed?

Jude: [00:07:00] It could affect either. So clopidogrel, the guidance that exists at the moment tends to recommend an alternative medication. But in some circumstances, if an alternative medication isn't appropriate or isn't safe either, then it may be a change in dose that's recommended. But this could vary between medication and vary between gene.

Florence: So is pharmacogenomics being used in the clinic day to day to help inform our routine care?

Jude: Yes. There are a few examples where pharmacogenomic testing is recommended and done in the clinic.

[00:07:30] One is a gene called DPYD, and variants in this gene can help predict whether someone has a serious, possibly even fatal reaction to certain chemotherapy agents.

Another example is a gene called MT-RNR1, which helps predict whether someone may develop hearing loss to certain very strong broad-spectrum antibiotics. So yes, there are already examples where a test is available to be ordered, and it can help guide choice of medication and predict serious significant side effects.

Florence: [00:08:00] Well, I think we'll finish there. Thank you so much, Jude, for coming on. It's been so interesting.

Jude: Thank you very much, Florence. I've really enjoyed it. And thank you very much for the invitation and for having me on the podcast.

Florence: If you want to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk or wherever you get your podcasts.

We'd also love to hear what you think. Do you have experience with any of the topics we've covered, or is there anything else you want us to explore?

[00:08:30] Let us know by commenting wherever you listen. See you next time

Advances in genomics are making it possible to develop treatments for individual patients with rare genetic conditions. But how can we get these treatments to the people who need them when traditional medicine development is designed for much larger groups of patients? 

In this episode, our guests explore the challenges of developing and approving personalised medicines, and how researchers, regulators and patient advocates can work together to bridge the gap between scientific advances and patient access. 

Our host Sharon Jones is joined by: 

Dr Dan O’Connor, Executive Director Regulatory, Association of the British Pharmaceutical Industry (ABPI) 

Julia Vitarello, founder and CEO of Mila’s Miracles Foundation 

Professor Rich Scott, CEO of Genomics England 

If you enjoyed today’s conversation, please like and share wherever you listen to your podcasts. 

 “The technology's there, and it's now just saying, "Well, actually, can the system catch up?" And that's really the clear message I think we have to do. We've got to somehow align with the fast-evolving opportunities that new technology will offer us, and ensure that patients get the medicines they really need.”

 

You can download the transcript, or read it below.

Sharon Jones: Hello and welcome to Behind the Genes, the podcast that brings you the stories, research, and innovations shaping the future of genomic healthcare. For decades, medicines have been developed and tested for large groups of people, but advances in genomics are opening up new possibilities, including treatments tailored to an individual's genetic condition.

So how do you adapt a system built for thousands of patients when there may only be a handful of people in the world who could benefit from a  particular treatment?

[00:00:30] Today, we're exploring how researchers, regulators, and patient advocates are working together to rethink the way new medicines are developed and approved.

I'm Sharon Jones, and joining me today are Dr. Dan O'Connor, executive director regulatory, the Association of the British Pharmaceutical Industry; Julia Vitarello, Mila's mum, and founder and CEO of Mila's Miracles Foundation; and Professor Rich Scott , CEO of Genomics England.

[00:01:00] By the way, you're going to hear a powerful story from Julia about her daughter, Mila.

Sharon Jones: If you want to hear it in full, the episode is called Mila to Millions, and you can find it in the episode description. Julia, I'd like to start with you. You've shared your story with us on the podcast before, but for listeners who may not know it, can you briefly explain what's brought you here today?

Julia: Yeah. Thank you, Sharon.

[00:01:30] My daughter, Mila was born completely typical and was running around and hiking and singing and playing like other children until she was six when she was diagnosed with 100% fatal rare genetic disease called Batten Disease. And I was told in just one minute that my daughter would lose all of her abilities and die in the next few years.

As you can imagine, my life in many ways ended in that moment. All my hopes and dreams of my daughter just were erased in one minute to the next.

[00:02:00] But I saw her fighting. I saw her lose her vision. I saw her lose her ability to eat by mouth and have a G-tube put in and start having up to 30 seizures a day, and she was still smiling and laughing.

And I just said, "You know, if she can fight, I can fight." And I started a foundation and raced against time alongside Boston Children's Hospital and Dr. Timothy Yu. And in a very miraculous, Herculean effort to save my daughter's life, we moved to Boston one year later, and my daughter started receiving a medicine called Milasen that was named after her.

And the reason it was named after her is because while her condition was already very small with only 25 children in the world at the time, she was the only one that shared that specific mutation and the only one that could benefit from that medicine. And at that time, my daughter then became the first person in the world to receive a medicine for one person.

It stopped her disease for the first year, um, but it wasn't in time for her. When she was 10, she died.

[00:03:00] And the reason that I am still here is because my daughter showed what was possible, that we now have the incredible science and technology to be able to find the root cause of disease, often a single mutation, and design a medicine, even if it's unique to one person.

And so I have been on a mission here to try to figure out how to help the millions of other families like mine in need.

Sharon Jones: Julia, thank you for sharing that. I mean, you know, it's a difficult listen and, you know, thank you for kind of going through what you've been through for, you know, numerous times on this podcast and sharing with listeners how, how hard that was.

Milia's story is incredibly powerful, and what really comes through is how much you fought to find answers. You know, that advocating, that determination, and how that journey has gone on to open up possibilities for, for many others. So, thank you for sharing that.

So Dan, to help us understand the system that families are currently navigating, can you talk us through what happens when a treatment is discovered and what currently has to happen before a patient can receive it?

Dan: Yeah. Thanks, Sharon, and thanks, Julia, for highlighting Milia's story. It's been really inspirational, I think, for some of the work that we've seen in the UK. Yeah, so when you, when you get a discovery, it's just the beginning of, of the journey to patient access, and I think sometimes patients and families, I'm sure Julia can understand this as well in her story, that it seems frustratingly slow.

[00:04:30] There's a lot of different hoops and jumps that you have to go through to ensure what we all want for the medicines, that the medicine works, it's got what's called efficacy and that it's safe. And those are really important aspects to any new medicine. So once you've got that discovery, there's a number of things that have to happen, as you move through that medicine through initially what are called non-clinical studies.

[00:05:00] So those are the studies before you enter the clinic, and then hopefully you learn sufficient information about the medicine during clinical trials that you progress through to a medicine that you hope the benefits are gonna outweigh the risks. And it's really important that we do those tests so that we don't create medicines that don't work as well as they should.

But equally, we have to balance the timing, that we have to try to really be careful around missing the opportunity to treat children as early as possible because that can be really important in their disease.

Sharon Jones: [00:05:30] And in terms of kind of how long that takes, what kind of timeframe are we looking at?

Dan: I think traditionally we always said it takes almost 10 years, sometimes longer, to develop a medicine. I'm really pleased to say that I think things with the really exciting 21st technology that we've got, things are definitely moving faster now, and I think we are seeing the huge opportunity, the advances in diagnostics, in the life sciences, using even synthetic data is really coming through.

[00:06:00] So data that is generated using different computer programs. All of those, I think, are converging in a way that's really, really exciting. And then we have these new treatment therapy modalities. So cell therapies using I'll call oligonucleotides, so genetic therapies, gene therapies. So we're at an amazing time of opportunity.

I think what we really need to do, and we've done a lot of this thinking in the UK but also in other countries, is so how do we really bridge the science to the patient, and how do we ensure that we don't put up barriers, but we, we make sure that the journey to treatment is as safe as possible.

Sharon Jones: [00:06:30] Thank you. And so one of the initiatives around putting that into practice is the Rare Therapies Launchpad. So Rich, can you explain to listeners what the Rare Therapies Launchpad is, and how is that helping to deliver this new era of individualized medicines?

Rich: So the Rare Therapies Launchpad is a collaboration of a number of different parts of the system in the UK and people who really want to change how rare therapies can have an impact for patients and families. [00:07:00]

We've heard from Julia, and Julia's been at the heart of the Rare Therapies Launchpad from the outset, really setting that, the clarity on the challenge. As we've heard, these rare conditions can be really serious from the outset. The potential impact on and, and often with quite high level of confidence we can say there will be a, you know, really difficult course for someone with a particular diagnosis.

[00:07:30] What we need to do is look at that journey, which we know we've heard can be, you know, months, in fact years, substantial numbers of years in the standard way in which therapies are identified, tested, and validated in terms of their impact, and really say, "How can we bring together different bits of the system and look end to end and say, 'How can we speed this up?'"

Because the balance here for serious rare conditions that have really challenging and, you know, bad outcomes for patients means that we need to do better than we are today. So it's looking across the end to end. So saying, "How can we find answers for people soon enough that we can even be thinking about finding a treatment?"

Then, how can we move from just finding an answer to very quickly, and not just in families, in situations like Julia, where Julia had to be so proactive and creative in finding a path and finding a group like Tim's, all of this was above and beyond, outside the norm.

How can we make that process with the new science that's coming along, with our ability and the infrastructure we have in the UK to hold data in ways that should make it possible to find these answers sooner? How can we streamline that and how can regulators and policymakers adapt the approaches so that they're proportionate and work, and that this is a cost-effective approach end to end?

And finally, how do we do that not just thinking about it one patient, one family at a time. How can we actually recognize that the current setup is really challenging for rare therapies? The UK is uniquely placed to provide quite a few of those links in the chain that are already there, some of the basics.

But also, for example, our regulator, the MHRA, has shown real open-mindedness in terms of saying, you know, "We want to look at what, what needs to change so that this can work, so that this is sustainable, and so that the evidence is there. This isn't about saying we move away from expecting that evidence.

[00:10:00]  It's about learning from early experience how we can create a system that really works in that joined-up way, and that's what the Rare Therapies Launchpad is about.

Sharon Jones: Thank you. It feels like there needs to be - you've touched on that kind of collaboration piece and, you know, the stuff around funding and the cost of it all and the speed this needs to happen.

Meanwhile, it does make you sort of wonder how, how possible this is and how quickly this can happen.

[00:10:30] So Julia,  having seen this current process from the sort of patient and the advocacy side, what do you think regulators and the wider healthcare system need to understand about the lived experience of families trying to access these kinds of therapies?

You were racing around trying to find answers, raising your other children. What do you think needs to change?

Julia: That's a good question. I mean, I think the reality, what I learned in this was that the system was obviously made for population medicine, for large diseases. And when it comes to genetic conditions, there aren't that many that are large that fit the current system, and one might say that that works really well if you have tens or hundreds of thousands, or probably hundreds of thousands and more probably per patient, patients per medicine.

But for genetic diseases, maybe that's a dozen that are large. And there are 10,000 that are small. My daughter's was just one of those, right?

[00:11:30] And a system made for, like Dan said, for 10 years, maybe even if it's less, it's still, you know, eight years and probably nearly a billion dollars or pounds, and it's just too much, right?

And even when you whittle it down to a smaller clinical trial, unfortunately, we not only have 10,000 small genetic conditions, but those patients are being further sub grouped, like we saw with Mila, by mutation, which means now we have tens of thousands of very, very, very small groups of one or a few or a dozen or so, and the system was really not made for that.

[00:12:00] And so I think that regulators and the system in whole needs to understand that science is changing, and we have the ability now to pinpoint this root cause. And then as a result, we now are going to have extremely small cohorts of patients, and we're gonna have 10,000 plus of them, you know?

So we're gonna need to change the way we do things, and I think what I've learned is a few things.

[00:12:30] One of them is parents selling  cookies and lemonade and raising millions, and clinicians becoming drug developers and also having to raise money, often with grants, and somehow dropping everything they're doing for, you know, a one or two-year sprint for a single child, is there's nothing sustainable or even scalable about that.

So, what I've also learned is that changing a mindset is extraordinarily difficult for almost all humans, and it is very hard after many, many decades of doing things a certain way to accept that the status quo is just not acceptable. And parents are learning that their children are amenable to today's incredible science and that they just can't access it, not because of science anymore.

That used to be the problem. You couldn't find Milas and you couldn't certainly make medicines for them, but now you can. And so I think when parents realize that, it really becomes an incredible moral imperative and, and you can't have the regulator, for example, impede access just because they say that this is just how you do it.

[00:13:30] So I think the MHRA is doing a really great job at starting to open that door and starting to shift the mindset, but that's what we need.

Sharon Jones: Yeah. Thank you. And, and one of the things you touched upon is evidence. Dan, what counts as enough evidence where there may only be, like, a handful of patients worldwide?

Dan: I think as Julia said, I think it's increasingly recognized by regulators and others that it's just not feasible to collect the type of evidence that we would have done in the past.

[00:14:00] And in rare diseases, you have many different challenges when you're thinking about collecting that evidence. As highlighted, you've got small numbers of patients.

It's harder to design the clinical studies. Many rare diseases are positioned in the paediatric setting, so for children, and that adds to the complexity. Smaller populations mean that the data that you get is often more likely you'll have missing data, so you might have the wrong interpretation of that, of that data.

[00:14:30] And, and often in rare diseases, we don't really always understand the natural history, so how, how does the disease progress? So it's really important that when we're thinking about collecting that data, we measure the right things that are important to patients. And sometimes that's missed because we don't know what to measure, and we don't know how to measure those really important things.

And it's often families and the patients themselves that will tell the regulators, "No, no, I saw a difference in my child. I saw that difference." And the question is, how do we capture that in a meaningful way?

[00:15:00] But I think the really good news is that we increasingly have the tools to do that using digital technology and what are called wearables, so you can sort of have opportunities that we didn't have in the past to be able to, to monitor and collect that evidence.

But there is definitely a need for that mindset change. I think we are seeing that mindset change with regulators. I think regulators want to authorize drugs that work well in patients, but they also wear the hat of ensuring safety for those patients.

[00:15:30] And I think we are seeing a shift in the thinking around how we measure the benefits and risks of medicines development.

But I think there are still a number of challenges that we still need to try to resolve to make sure that patients get the medicines as soon as they possibly can.

Sharon Jones: What else is needed? What do you think will sort of, you know, move the dial even further?

Dan: There's, there's no doubt there's a need for a sort of cultural shift across the ecosystem. You know, some drug development is considered to be quite conservative.

[00:16:00] It's always done a certain way, and so it's kind of moving through thinking about a new way of working. I think what we really need is some good examples of how we can get it to work. As Rich said, that end-to-end pathway, how do we really ensure that we can demonstrate that we can do this, and that we can do this in a way that is safe and proportionate, and then we can scale that, and we can bring out the right roles and responsibilities, the right accountability, and that we can deliver these medicines at the right time to the right patient using the 21st-century science that we now have in our hands.

[00:16:30] And I think we are getting there. We're starting to see some really good examples of where treatments are coming through to patients. But we really need to accelerate that. Ninety-five percent of rare disease patients don't have any opportunity for therapy. And we, if we continue down the current approach to how we develop drugs, I mean, we'll be here for thousands of years before we've managed to reach every single patient, and I think we collectively all think that's completely unacceptable.

[00:17:00] We have to work harder to try to think, "How can we move faster, but how can we move faster in a way that is proportionate and safe and really has the patient focus in mind?"

Sharon Jones: Yeah. There's also something about access as well. I know, Julia, you touched on that point about access and how do people find their way through what seems like a very complicated and not necessarily joined up system at the moment.

Sharon Jones: So making this work requires a huge amount of collaboration, as we've kind of just touched upon.

[00:17:30] Rich, with that in mind, how important is it that organisations across research, healthcare, regulation, and patient advocacy work together as these rules change and develop?

Rich: It's absolutely crucial. As, as we've been saying, this is about a sort of an end-to-end long journey.

You heard from Julia right at the beginning about what she had to go through and how much of that took that, that tenaciousness, that ability to navigate a really complicated process all the way from a family back to a family receiving something that should have some benefit via healthcare, via researchers, understanding all of the different pieces in the chain.

You know, the first thing, and you've heard it really clearly here, the current system was not designed to work in this setting for, for rare therapies. The first thing that's really important is to, and that's happening through the Rare Therapy Launchpad and the work more  broadly on rare therapies here in the UK, is recognising that the current system is not set up to work for this.

The status quo is not okay. We need to have this as something that is the expectation for patients and families with rare conditions. We've got a number of the links in the chain that mean that we're relatively well-placed in the UK, but that doesn't mean  that we have all of them.

[00:19:00] So there are gaps, and there are linkages between the different pieces of the chain that need joining up. And it's only when you really come together and look, align on where you're all aiming to head and really do the, that detailed work to identify where you need to get better alignment, or whether you need to fill in a gap, whether you need to work with another group, another organization to make sure that that piece really works.

[00:19:30] And crucially, to have the families and the families' voice there to be at the heart of it and really be clear. This is about balancing risk and benefit. And the people who are going to be making those choices, they need experts to support and think about where we are, how we establish and use some of these technologies.

But the bottom line is this is putting people in a position to make the right choices with enough information about what we know about the benefits and what we know about the risks.

These are families in a situation where the risks of no action are often very clear. What we need to do is create a system that puts them in a position to be empowered to make choices without having to become experts themselves.

What's so exciting that it really is realistic for us to think about rare therapies being the norm for rare conditions. How can we get to that position?

Sharon Jones: Thank you. I mean, Julia, reflecting on what Rich has just said, what do you feel about that, having been through this yourself?

Julia: I mean, I think what Rich is saying is, is spot on, and I think that going back to the difficulty of changing mindsets, it really starts with that. So if people in positions of power at all the different pieces along the way of that chain that Rich described don't change their mindset then and just sort of default to how we've always done things, then we'll be here having this podcast and having the same discussion in 10 years, which is what that means actually is millions of children's lives around the world.

[00:21:00] It's been 10 years next month since Mila was diagnosed, and I've seen great progress in some ways, and I've also seen and experienced incredible frustration at the inability to realize that Science and technology are changing, and the system has to change with it. And I think that the Rare Therapies Launchpad was really started - I remember talking with Dan for the first time, and we sort of, like, picked it up and ran with it and put all the people, including Rich and Genomics England at the table to think, instead of just talking about this, how do we demonstrate it?

That's really where things change, 'cause it's great having the discussions, but until you actually start treating dozens and then hundreds and eventually more of children that have fatal and life-threatening conditions starting in the UK and, and you won't really see the system change because you might see words on paper and, and we have seen that with the MHRA, and it's really exciting.

It absolutely opens the door to doing things differently.

[00:22:00] But until you actually push these cases through and force everyone at the table to figure out something that's never been done, it just becomes hypothetical, and I've watched that now for so many years, and the only measure that I use to see whether or not we're successful, we as in the whole field, is very simple.

It's – are there exponentially more children like Mila being treated? And the answer is no. So whatever we're doing is not working. So we need to take it a step further now that people are actually changing their - they're looking over there and not over here, then now we need to actually make it possible for companies which can't exist in this space 'cause these medicines are not approved.

They're Hail Mary, one-off academic experiments until they're approved and until we're able to group many, many medicines that have a commonality within parameters at the same time. You know, going one by one, we can do the math. We'll be here in, I don't know, a few thousand years. So I think we've opened that door.

[00:23:00] Now we have to actually demonstrate, and I think to Rich's point, the UK is very, very well positioned to be the one to demonstrate that, but that does mean actually doing it and not just saying it

Sharon Jones: Yeah. And Dan, are you, are you in agreement with that?

Dan: Yeah, fully, aligned with that. I think we've got a really exciting opportunity in the UK.

I think we've got many of the pieces of the jigsaw, we've got to really pull them together, and we've got to demonstrate we can work it, at scale and then in a way that's really sustainable. Because if we treat one or two patients, that's of course excellent for those patients and their families.

But ultimately, with the fantastic work that Rich and the teams at Genomics England do and elsewhere, we're going to find more and more of these patients as we scale up our diagnostic capabilities in newborn screening and other opportunities. So we really have to fix this disconnect between the science and the patient.

We really have to do that.

[00:24:00] And I think through initiatives like the Rare Therapies Launchpad, the MHRA's new rare disease framework, there's really an opportunity to think differently. But not only to think differently, but to act differently. And I think if we can bring all those together, and we can demonstrate that we can do this, and as Julia says, if we can start to treat those patients and demonstrate visibly that we can do this and that we can do this at scale, then hopefully everything else will fall into place, and we can persuade policymakers and others that actually this is really something that we can do, and we can do it really well.

Dan: [00:24:30] And it makes an impact  not only to patients, but broader public health and the UK as a whole from an economic perspective because we can drive innovation in life sciences by creating the opportunities to develop and access medicines in the UK.

Sharon Jones: Yeah. It sounds like there's, there is that opportunity. It's just that drive and that thought into action and that collaboration piece just all coming together, and we're not quite there yet. So Rich, looking to the future, how can advances in diagnosis, screening, and personalised treatments work together as one connected system to deliver better outcomes for patients with rare conditions and the NHS?

Rich: Just reflecting on a number that we just heard, which is that 95% of patients with a rare condition don't have a specific targeted treatment that we can offer. I think, genuinely think, as I said before, we can shift from that, that being the exception to that being the norm, and to that being something which the whole health system is just able to deliver in the standard flow, and that we can continue to learn as we go so that this doesn't always have to be in a sort of very separate sort of trial setting.

We've heard from Julia, this is about sort of recognising that in many ways, each of the individual people who benefit from these treatments, often they're unique. We need to be able to continue to learn so that we can build that knowledge for those patients and those in the future.

Sharon Jones: [00:26:00] So we've covered a lot today from the challenges of developing treatments for a very small number of patients to how genomics, regulation, and collaboration could find a way forward.

Sharon Jones: But before we finish, I'd like to ask each of you the same question. What are you most hopeful about when it comes to innovation in medicines? And I'll start with you, Julia.

Julia: [00:26:30] I am most hopeful that the UK will be the place that actually will demonstrate regulatory shifts that instead of approving one medicine for one disease for one child at a time, it will really approve the process, a standardized process for developing those medicines, and that will allow for exponentially more children to access today's technology when they're actually amenable to it.

I think the MHRA's recent rare disease framework that came out earlier this year is very, very promising and opens the door.

[00:27:00] It's not all the way there, so it's gonna require even further shift. And my hope is that when sponsors, whether they are for-profit, non-profit, doesn't matter, show up to the MHRA, that they respond well to that and that they work over the next few years to really demonstrate that shift towards what I would call process approval.

I think the door is open to do that, so I'm very hopeful that the UK will create a blueprint and then other countries around the world, it'll be easier for them to understand what this is 'cause it's a concept right now, and then be able to replicate a version of that in other countries and then now we start seeing what we all hope, which is exponentially more sick and dying children to start with accessing today's incredible science and technology.

Sharon Jones: Yeah. Thank you. And Dan.

Dan: Difficult to follow that one, I think, but I would say, I mean, we live in an amazing time of new opportunity, and innovation is embedded in that. It's in, it's embedded in the science, it's embedded in the technology, it's embedded in the regulators. And so to me, I think we just need that clear alignment.

We need that shared vision that we can use the fantastic science that exists, the opportunity to treat patients with these new therapeutic modalities, and we can find this end-to-end pathway which will allow us to treat patients at scale in a sustainable way.

And I think if we look where we were maybe twenty or thirty years ago, the, you know, the blockers was the science.

[00:28:30] The blocker was the fact we couldn't do this. We just technically couldn't do it. That's no longer the case. In many disease areas actually, we've seen a fundamental shift in the opportunities. Have we got it all right? No. And there are areas we still need to learn so much more.

But the technology's there, and it's now just saying, "Well, actually, can the system catch up?" And that's really the clear message I think we have to do. We've got to somehow align with the fast-evolving opportunities that new technology will offer us, and ensure that patients get the medicines they really need.

Sharon Jones: Yeah. There's definitely something about pace there. And Rich?

Rich: So our vision as an organisation, and, and shared with the NHS from a genomics perspective, is a world where everyone can benefit from genomic healthcare. And I think what Julia describes is what we need to do for people with rare conditions and their families.

It's to really live up to that where that is a democratised routine access to what the science can allow with the evidence, with the support around it, with a health system able to provide it, and I'm really optimistic that we can get there.

Sharon Jones: Thank you. And on that positive note, we'll wrap up there.

Sharon Jones: A huge thank you to our guests, Dr Dan O'Connor, Julia Vitarello, and Professor Rich Scott for joining me today as we discussed whether we can change the rules of medicine.

Julia: Thank you.

Dan: Thanks for the opportunity. Thank you.

Sharon Jones: [00:30:00]  If you enjoyed this episode and you'd like to hear more, please subscribe to Behind the Genes on your favourite podcast app.

Sharon Jones: I've been your host, Sharon Jones. Behind the Genes is produced by Deanna Barac, Sophie McLachlan, Florence Cornish, and Patrick Wallace at Bespoken Media. Thank you for listening.

In this explainer episode, Rachel Brucoli, Deputy Director at the Medicines and Healthcare products Regulatory Agency, explains how we make sure that medicines stay safe and work properly. 

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, let us know on podcast@genomicsengland.co.uk.

Read more about the MHRA via their website.

You can download the transcript or read it below.

Florence: How do we make sure that our medicines stay safe and work properly? My name is Florence Cornish, and today I'm joined by Rachel Brucoli, who is a Deputy Director at the Healthcare products Regulatory Agency, also known as the MHRA.

And Rachel is here to tell us much more about the topic Well, firstly, Rachel, thank you so much for joining us today. It's great to have you on.

Rachel: Thank you. Nice to be here.

Florence: The first question I wanted to ask you is quite a big question and I guess the crux of this entire episode really. Um, but how do we ensure that medicines are safe and work properly before they get to patients?

Rachel: Yeah, it's an important question, isn't it? So in the UK, medicines are regulated by the Medicines and Healthcare Products Regulatory Agency or MHRA for short. And that's to ensure they, they are safe, they work correctly in a specified disease, and they're made to a high standard before they reach the public. In line with the relevant law, which is the Human Medicines Regulation, before a medicine is allowed to be placed on the market in the UK, the MHRA reviews safety information from clinical trials to ensure that the medicine does not cause unexpected or unacceptable effects.

We also review efficacy data from clinical trials to make sure that the medicine works in the disease or condition and in the patient population that the manufacturer claims it does. Um, another important aspect that's reviewed is how the medicine's manufactured. It's very important that the medicine is made consistently and that every batch meets agreed specifications.

Florence: And so you used that word regulation a few times. When we say that medicines are regulated, how do we do that? What does that process actually look like?

Rachel: Yeah. So different countries have different laws that govern how medicines are regulated. And as I mentioned before, in the UK, the relevant legislation is the Human Medicines Regulations.

In addition, different countries have different pathways or procedures for licensing of medicines, but it's worth noting that the types of data looked at by regulators is similar, and we've got harmonised standards in, in many respects. In the UK, different types of application can be submitted depending on the type of medicine under review.

So for example, the data submitted for a brand-new medicine containing a new active substance that hasn't been approved in the UK would differ from that submitted for a generic medicine.

The licensing process is triggered when a marketing authorisation application is submitted to the MHRA by a pharmaceutical company or a biotech company. And for new medicines, this application contains a significant amount of data that's been generated over, um, a large number of years.

Florence: Mm-hmm. Can you tell us a little bit more about that? What types of information are submitted to you in this process?

Rachel: Yes. So there's three main types of information that, that we receive.

Um, the first is quality data, and that provides evidence that the medicinal product can be made safely, reliably, and to a high standard. It describes what the medicine's made of, how it's made, and provides evidence that the medicine can be produced consistently.

The second body of data contains the results of the non-clinical studies, and there they characterize the pharmacology, and the safety profiles of the active ingredient of the medicine.

And the third section of the application is the results and analyses of all the clinical studies conducted with the proposed medicine. These clinical studies will have been conducted in phases, and they're designed to determine the optimal dose of the medicine needed to treat the specific disease and to provide evidence that the medicine works, or as we would say, is efficacious, and that's usually compared to placebo.

So, what's being measured in clinical studies are clinical endpoints, and they are specific outcomes or events that are measured to determine if a new treatment works.

So, I guess giving an example of that is a cancer medicine, um, where a relevant endpoint that could be measured might include overall, an increase in overall survival or a reduction in tumour size. Additionally, some other important, outcomes could be patient-reported, such as effects on quality of life. So these clinical data will be analysed using appropriate statistical methods, and then this analysis will be presented to the MHRA as evidence to show that the medicine works or is efficacious.

Another important aspect is the data from clinical studies in respect of safety, so they're also used to determine the safety profile. Standard clinical development programs can involve at least a thousand patients, so a reasonable amount of data can be collected on common and less common side effects.

In terms of what kind of happens when we receive the application, different assessors of different disciplines, so for example, doctors, pharmacists, toxicologists, scientists, chemists, review the data received. We check the accuracy of what is being given to us by the, the applicant, and we take a decision on the overall approvability of the medicine.

What is really important to note is that a medicine will only be approved if the MHRA, um, believe the evidence of benefit outweighs any identified risks.

It's also important for people to know where they can get information on the data that's been reviewed by the MHRA. So, if anyone would like to know more about the data that's been considered and the assessment decisions, then they could look on the MHRA website where we routinely publish public assessment reports for all the applications, and that's including those that we refuse. 

Florence: You mentioned clinical trials a couple of times, and I should say for any listeners who might not know that a clinical trial is, is a research study that involves volunteers who are essentially testing out a new medication or a new intervention, and the results from that, as you mentioned, um, will kind of give you information about its safety and, um, any side effects and whether it's working.

I was wondering, are there any other ways that you get information about a medication aside from these trials? Is there anywhere else that you're looking for data as well?

Rachel: So there could be literature data that people submit to us. I mean, primarily for very new, um, drugs, the information comes from clinical studies.

However, you know, once we have approved something, um, we do continue to collect safety data on, on products. So, um, at the time of licensing, we will, yeah, that the main, the main part of the, the clinical data comes from those controlled clinical studies. But in terms of kind of post-marketing, we do encourage patients and healthcare professionals to report any suspected side effects to us through our yellow card system.

In actual fact, companies can continue to carry out kind of further studies, um, after they've got their approval, and that can be to collect more, more safety or even efficacy data.

It's important, I think, to say that once we've given something a licence, that's not where it stops. That we do, and can take regulatory action if, you know, during the life cycle of a product, it emerges that the risks associated with that product start to outweigh the benefit that, that we originally saw.

Florence: Yeah. Um, and obviously, the MHRA play a vital role in deciding whether to grant a licence for a medicine. Um, but is there anyone else as well that has a level of responsibility or plays a role in this process too?

Rachel: Yes. So during that initial licensing phase when we're reviewing that application, we will, um, have the opportunity to ask questions of or even raise objections with, with the, the applicant of the company that submitted that application.

They will have a few opportunities to provide further data or different analyses that might allay our concerns. But a really important, um, group of people that do contribute to our decision-making, um, are our independent experts that we can use to, to get advice.

So we have expert advisory groups and also the Commission on Human Medicines or CHM as, as we would commonly refer to it. And these are very important because many of the experts on CHM, for example, are practicing clinicians, and so they do give us insightful advice because they're the people that are treating the patients on a daily basis.

We also, um, where possible, try and bring in patients and public perspectives into consideration at various stages throughout the kind of regulatory life cycle of a, of a medicinal product.

And so patient public involvement engagement is very important to gain wider perspectives, and it helps us to kind of put patients first, which is really at the heart of what, of what we do.

Florence: And finally, of course, I have to bring us back to genomics because this is a, a Genomics 101 podcast. Are there ways that genomics is playing a role in the way that we develop medicines?

Rachel: Yeah. I mean, genomics plays a vital role in many ways. Um, mapping human genes and identifying DNA mutations that cause disease allows companies to develop targeted treatments and personalised therapies. I mean, one such area that a lot of people may be familiar with is pharmacogenomics, and that's where DNA can be used to understand how an individual's body will break down a medicine and can help set appropriate doses for that particular patient, and therefore reduce any kind of potential unwanted effects.

Genomics can also help diagnose rare genetic conditions or even guide the treatment of specific types of cancer. And a good example of this is breast cancer. Um, so where understanding the activity of specific genes inside the tumour tissue that's taken at biopsy, that can help guide treatment options to give the best outcome for that particular patient.

I mean, moving on into kind of terms of rare diseases, 3 and a half million people live with a rare disease in the UK. That equates to 1/17. Um, lots of stats, but eighty percent of these rare diseases have a genetic cause, unfortunately, though, less than 5% of these have an approved treatment at the moment, and that's largely because there's lots of challenges with developing medicines for rare diseases.

It's just simply not possible to do those kind of large-scale clinical trials that we were talking about earlier. Um, and so it's, it's not easy to get a sufficient amount of evidence of safety or indeed of efficacy. I mean, in some cases, the, the, a genetic disease could actually just affect one person.

So the MHRA does realise this is a pressing need, and it's a growing area at the moment. And so we've developed a rare disease, um, therapies regulatory framework, and that aims to provide a flexible regulatory approach to ensure that efficient development of medicines, addresses this high unmet, clinical need.

It's probably worth noting the pathway is not specific to any particular technologies, but we do anticipate that several gene therapies and individualised medicines will come through this pathway. And so it's a really, really exciting time in this field.

Florence: Yeah. Well, I think we'll finish there. Thank you very much, Rachel, for joining us today. It's been such an interesting conversation.

Rachel: No, thanks for having me.

Florence: If listeners want to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk or wherever you get your podcasts. Thank you for listening.

In this episode of Behind the Genes, we explore Black communities and health research. Our guests discuss why some people feel research is not intended for them, how historical mistrust affects participation, and what needs to change to make research more inclusive, transparent and beneficial for everyone. 

Our host, Sharon Jones, is joined by: 

Professor Segun Fatumo - Professor and Chair of Genomic Diversity at Queen Mary University of London

Christella Matoko - Project manager at Genomics England

Hazel Attua - member of the Participant Panel at Genomics England

We also hear from Mica and Mary, who took part in the Our health, our stories video on YouTube, who share their reflections on why taking part in research matters for Black communities. 

As mentioned in the episode, you can also listen to our latest Genomics 101 episode, What is equity in healthcare?, to learn more about what equity means and why it matters in health research and care. 

“Engaging in research is bigger than you. It shapes your community, and it shapes the lives of the children coming in the future.” 

You can read the transcript below.

Sharon Jones: [00:00:00] Hello, and welcome to Behind the Genes, the podcast that brings you the stories, research, and innovations shaping the future of genomic healthcare. Today, we're exploring Black communities and health research. Why do some Black people feel that research isn't intended for them? What role does trust play in participation?

Sharon Jones: And what needs to change to improve health outcomes now and in the future? I'm Sharon Jones, and joining me today are Christella Matoko from Genomics England, [00:00:30] Segun Fatumo, Professor and Chair of Genomic Diversity at Queen Mary's [University of] London, whose work focuses on improving representation and equity in genomic research, and Hazel Attua, who's a member of the Participant Panel at Genomics England.

Sharon Jones: A warm welcome to everyone. So before we dive into these topics, let's start first to try and understand how people perceive research and how that can often influence whether they feel it's something for them. So Christella, I'd love to come to you [00:01:00] first. What comes to mind when you hear the words health research?

Christella: I think when I'm talking about health research, what comes to mind is the opportunities to understand certain health conditions in different communities, and it's about understanding that we can get better treatments, and these treatments can prevent health inequalities. Although I might look at it from this lens, the whole of the Black community might not.

Christella: I have the knowledge of medical care. I work in Genomics England, [00:01:30] so I understand the benefits of, um, health research and how it can improve outcomes within the healthcare. But when you speak about it in terms of the Black community, research doesn't necessarily sit naturally because of all of the historical mistrust that we've, you know, encountered.

Sharon Jones: Yeah.

Christella: So for me, good healthcare research should ultimately lead to better outcomes for everyone. And I think when I hear [00:02:00] health research, that's like what I like to think about.

Sharon Jones: Yeah. Thank you. Thank you for sharing that. And, and Hazel, like coming to you, does that reflect what you've seen or experienced?

Sharon Jones: You know, do you feel that research feels relevant to Black communities and why do you think some people may feel hesitant in, in taking part?

Hazel: Yeah, I mean, I completely agree with Christella. I think it's difficult for people in the Black community to sometimes trust when research comes out [00:02:30] because previously there's been a lot of mistrust around research because there hasn't always been a lot of research within the Black communities.

Hazel: Like when we talk about research, when we talk about, um, for example, with National Genomic Research Library, so when I used to do work with Genomics England-

Christella: Mm.

Hazel: I specifically was, um, working on the National Genomic Research Library within, um, diverse data. [00:03:00] And so our role was to get more diverse data into the National Genomic Research Library.

Hazel: And so for those that don't know what that is, it's like a biobank. And so a biobank is essentially, um, where you help collect samples. So if you've decided to get into research, it's collecting samples, processing samples. So when we decided to do the initiative or when Genomics England decided to do this initiative, I thought it was [00:03:30] amazing because essentially not that much research was done previously for the Black communities.

Hazel: And specifically for sickle cell. So to be able to do this, to be able to help understand the background for sickle cell for the Black communities, it's amazing. To be able to get more treatments and interventions, it's great. But like Christella is saying, like, it's interesting to see different people's [00:04:00] perspectives because, again, the trust and the misconceptions around research is different in everybody's eyes because of the, the lack of research that's been done before.

Hazel: And so the hesitation around it is like, "Why, why is it only coming about now?" Like, "Why are we doing it now?" But that's the thing about the UK, we're such a diverse population, and it's amazing. So research needs to reflect that. [00:04:30]And so I think hopefully going forward, it actually does do that because we do need treatments and interventions that actually reflect the community.

Hazel: Otherwise, we're not gonna get anywhere when it comes to medications, like, health data that actually reflects everyone.

Sharon Jones: So we're gonna hear from Mary now, who's a research nurse and midwife, who shares her thoughts on why people [00:05:00] may be hesitant in taking part in research.

Mary (Clip): Within the Black community, historically, the lack of participation in research stems from a lack of trust. Historically, I guess the best way to put it is why would I go to a party I've never been invited to? And it's trying to get people to understand that narrative has changed. The lack of trust should never be dismissed.

Mary (Clip): It's not a, a myth. It stems from [00:05:30] somewhere. However, there's been so, so, so much change, and I'm hoping that people can see that there are people that really want to make this change for you, for me, for us, for our community. It's so important that, yes, we still hold on to the history of where research is coming from, but we need to paint the picture of the future.

Sharon Jones: So Mary's analogy of being invited to a party you've never been to really gets to the heart of that question around trust. So [00:06:00] Segun, I'd love to bring you in at this point. From your experience working to improve representation in genomic research?

Sharon Jones: Can you explain to listeners why historically Black communities have felt disconnected to research, and what needs to change to make it feel like it's something for the community rather than something that's being done to the Black community?

Segun: So I think we need to get to a point where we acknowledge that there's mistrust.

Segun: So some Black community are fed the old, kind of research that is being done on them and not being done with them. You cannot just show up in a community and start asking for their blood sample or asking for their data, and you just do research on them without, uh, proper community [00:07:00] engagement, without getting them involved, without asking them what are the things that are really very, very important, uh, to them.

Segun: I think, uh, we researchers and also institution and as well as a nation, UK, where we are taking a lead in global genomics, needs to get to a point where we understand that the trust h-has gone, and, uh, we should not expect the Black community to [00:07:30] give us their trust.

Segun: We need to get to a point that where we earn that trust from them, and we're able to do our study on them. So currently in the UK, if you look at some of those, uh, very successful, uh, Black community is really underrepresented. And one of the reason why you hear that is they say that the Black community, they are very hard to reach.

Segun: So they're hard to reach because of the same issue. Community engagement has to [00:08:00] be done in a proper way. Yeah, you need to do research in a way that you go to those Black community and don't expect them to come to you.

Segun: And we see a lot of that during, uh, during COVID. You see that many, uh, Black community were very hesitant to participate in any vaccine. So we need to get to a point where Black community earn our trust.

Sharon Jones: Thank you. Christella, [00:08:30] what do you think about the role that trust plays in deciding whether to participate in research?

Sharon Jones: You, you know, given that you've worked on the Generation Study.

Christella: I think trust has to be earned, and I think Segun has said it perfectly here in terms of working with the community and coming into the community to understand how the community works. This mistrust that we're talking about is not something of today.

Christella: It's something which has been reported on. It's something which we have seen. It's something which has-- it's not a made-up thing. [00:09:00] So when, um, when organisations say Black communities are harder to reach, there is reason for it. That cannot be an excuse not to actually participate with those people in the community to show the difference in which we have made over the years, to understand that we are making changes with the transparency of what we do, you know, creating, um, work which you know where your data is going, because at the end of the day, I'm giving away my [00:09:30] sample.

Christella: I want to know who will have access to that sample, where that sample will go. And until we get to a point where we understand that trust has to be earned, it's always gonna be quite difficult if we think Black community are just gonna participate because there's a research available.

Sharon Jones: And that's a really fair point. And what do you think, given your sort of experience, what do you think helps build that trust in practice?

Christella: I think first of [00:10:00] all, um, not telling and actually going into communities and understanding. So when we talk about the Black community, it's not just a small group of people.

Christella: There are Black Caribbeans, there are Black Africans, there are people from different tribes within different countries. So it's not just a, a one-size-fits-all kind of thing here. Yeah. So it's understanding what you're actually trying to achieve, going into places where the Black community [00:10:30] actually congregate, so whether that is church, whether that's community events, whether that's, uh, Black-based events, actually going in and understanding what is it that you would like us to do to show that we are not the research of, you know, the, the early 19th century?

Christella: What have we done to show that we are progressing in terms of equality? What have we done in terms of how we're using your data? All those things there, it's not about [00:11:00] things being done to the Black community. It's the, it's the partnership, I think, that needs to be at the forefront of what we do now.

Sharon Jones: Yeah. Yeah, and Hazel, coming to you, what do you think enables that participation?

Hazel: Again, 100% agree with Chrisella and Segun that it's all about coming to the community and building that trust because it's, it's difficult, and it's about showing up and not just [00:11:30] showing up once.

Hazel: It's about consistently showing up and consistently building that trust because it's easy to do a workshop or do an engagement once and tell everyone this is what you're trying to achieve. But if you consistently show everyone who you are, what the research that you're trying to do is, it's not just about telling them about the research, it's understanding who they are before you actually trying to gauge them about the research because, like, [00:12:00] it's breaking down their walls and breaking down their barriers.

Hazel: As a Black community, we build up these walls, and I say it as we because we've been let down so many times and-

Hazel: like, I say this from my experience, from times where, from the sickle cell community, for example We had treatments that were brought in, so there was, for example, crizanlizumab and [00:12:30] voxelotor that were brought in, and they were approved in, uh, like, 2023, 2024.

Hazel: But then in 2024, they were then taken away. So early '24, crizanlizumab was then taken off the shelf.

Sharon Jones: Right.

Hazel: And then late September, October, voxelotor was then taken off the shelf, and that's very disheartening for patients with sickle cell. And in the Black community, you can see how also people have been let down [00:13:00] again and again

Sharon Jones: Yeah.

Hazel: in not just healthcare, but in general, like the stigma, the discrimination. And so to come in and just ask people to just get involved in research and then done and dusted-

Sharon Jones: Mm-hmm ...

Hazel: it's all about treating them as people before asking them to get involved in research. We have to be treated as people before we get involved in anything.

Hazel: So it's, I think that's how you get [00:13:30] people to be involved and enable them to get involved in research.

Sharon Jones: Yeah.

Hazel: It's just treating them as people before anything else.

Sharon Jones: And were there any factors for you that, you know, at first you might not have felt comfortable taking part, and what were sort of deciding factors that made you to get involved and participate?

Hazel: So for me, coming from, like, a personal point of view, 'cause I was on voxelotor, um, for me It, again, it was very disheartening- Mm-hmm ... um, when it was taken off the shelf, [00:14:00] and it was done very quickly overnight.

Sharon Jones: Right.

Hazel: And so for me, it's kind of one of those things where it's like, hmm, what do I do? Do I just not trust the system anymore?

Sharon Jones: Yeah.

Hazel: But then, like the flip side to that is, okay, we've had this drug, and it actually worked for me very well. And the look of that is, okay, so we've had this drug. It was amazing. The potential is we'll get more drugs that will be like this. And so [00:14:30] going into the Diverse Data program and thinking about how we approach people to say, "If you can get involved in this study, the likelihood is we actually might get more drugs, more treatments, more interventions that are going to be as amazing as Voxzelator was."

Hazel: Because the likelihood is we've had a drug that was great, and we could actually get more drugs that could be available.

Sharon Jones: Yeah.

Hazel: But we need research to do it because at the end of the [00:15:00] day, it's research. It's gonna take time, and the results are always gonna shift up and down. So yes, it can be disheartening, but at the end of the day, we've got to keep trying.

Hazel: Otherwise, if we don't keep trying, then we're not gonna get anywhere.

Sharon Jones: Yeah.

Hazel: So I had to ... You have to bite the bullet sometimes, and that's all you can do. So yeah, I think that was what shifted my mindset from not [00:15:30] -from being upset about it to then actually looking at the positives around it.

Sharon Jones: Yeah. Yeah. I mean, that is a difficult reframe when something that is working so effectively is suddenly kind of shelved, uh, very quickly like that.

Sharon Jones: So changing your mindset couldn't have been, couldn't have been easy. Christella?

Christella: When we're talking about what, what, um, Hazel has just said in terms of something was available to everyone and then it wasn't available, and then that goes again to what I say about [00:16:00] transparency. I think if there was more transparency about what was happening with this particular drug in the community, there would be that, that trust that would have, there would be more of an understanding, there would be more of a, like Hazel's taken the, the stance of, "Okay, I will still trust in the research because I believe something better will come along."

Christella: It's because of also her knowledge within the research. She's been around- she's been around Genomics England, she's been with people that research has really helped. But those in the [00:16:30] community who haven't, they feel disheartened about this, and this is why I say transpare- transparency about what is happening is so important with our community 'cause we-- so we don't feel like things are just being done to us, we actually understand the reasons behind it.

Christella: So for me, there's a few points. It's having people who represent the community actually being clinicians, um, being researchers, you know, leading in these community spaces, the transparency, the [00:17:00] long-term relationship that Hazel was talking about within the community. It's not you come in once and then, you know, you get what you want, and then you leave again.

Christella: It's also sharing the findings, and it's also having a trusted message constantly in order for the Black community to actually participate in these research.

Sharon Jones: Thank you, Christella. So we've got these themes of, like, consistency around trust, around communication, transparency. So Segun, I wanted to come to you now.

Sharon Jones: So why-- if people at [00:17:30] home are still trying to understand why this is important, can you explain to them why representation matters in research, and what happens when communities are not adequately represented in research? What is the impact, and how does that show up?

Segun: So representation matters in research because eventually a decision about our health will need to be made, uh, with this.

Segun: I give you an example of, uh, a, a drug that we have today, medication we have today that is helping to lower cholesterol. So that medication came to be because some African ancestry individuals were involved in a study. So in that study, they found that those African individual, they have, uh, some genetic variation that is helping them to naturally, uh, lower their cholesterol.

Segun: So because they included those African ancestry individuals, so we had, uh, PCSK9 inhibitor where the medication was derived. Now this medication is not only useful for, uh, people of, uh, Black community, but for everybody globally. So helping to lower cholesterol and prevent heart attack.

Segun: So we are doing ourself harm if we continue to exclude some people from, uh, from res- from research. Diagnosis is very important. So some tool for [00:19:00] diagnosis might not be appropriate for an ethnic group or, or ancestry or maybe, for example, in this case, a, a Black community.

Segun: In a research where we get the right diagnosis, uh, the right treatment, uh, for the right people, for the right community. So we cannot just do, uh, all the research on one particular community, and it posts the finding on another community. So representation is really, really very important, not only among, uh, people that participate in research and also in research leadership.

Segun: It is much more easier for Black community, uh, to show interest in research if they see somebody that look like them. So the, the representation has to be at every layer, both the [00:18:42] participant and also at the, at the leadership level.

Sharon Jones: Yeah.

Segun: I give an example for, for my study, uh, genetic risk score, in most of the study that we've done, we've seen that where you develop a genetic risk score from one population, and you try to, uh, transfer that, uh, genetic risk score to a Black community, they do very poorly.

Segun: So we need to include-- We need to be able to get to a point where we involve a Black community adequately in studies so that we can [00:20:30] be able to develop, uh, the right genetic risk score to every, every community.

Sharon Jones: Yeah.

Segun: So represent-representation is really, is really key. Uh, it's not just about fairness.

Segun: It's about the, you know, accuracy. It's about, uh, you know, precision. It's about better healthcare.

Sharon Jones: Yeah, and it's like you say, it's sort of holistically, it's from participants, but also for people who are working in research that also aids the sort of uptake in participation if you see people who look like you.

Sharon Jones: We're now gonna hear from Mica, who is a mum who took part in a Generation study, and she's gonna talk about why getting involved was so important.

Mica (Clip): I think as a Black woman, as a Black person, put yourself forward because the narrative at the moment is there's not enough research, and we're getting all these sort of doom and gloom headlines about, you know, Black maternal outcomes, Black men and prostate cancer, for example. And I feel like if we as a community don't put ourselves out there and make ourselves available for research, that narrative isn't gonna change.

Sharon Jones: So, Segun, I'd like to come back to you again. On the flip side of that, how can research organisations better involve Black communities? And are there concerns that we've talked [00:20:38] about today that have, uh, been acknowledged and addressed effectively?

Segun: So the first thing is that we need to acknowledge there's a problem.

Sharon Jones: Yeah.

Segun: And we see the Black people are not really, you know, participating in research because of trust. So how do we overcome that? One major thing is relationship or what I call, uh, community engagement. So community engagement is not community consultation. You know, you want to do research, you just [00:22:30] show up at that time you want to do research.

Segun: You know, take people's blood sample and go away. So community engagement starts much more years ahead before... So when you have the right relationship with the community, it's much more easier to be able to do research with them.

Segun: So we have to ensure that, uh, people that are doing the research are also well represented. So we have people that, that look similar, people that understand the community, uh, people that live among the community, so it's much more easier to help, help us to boost the trust. So the third one that people don't talk a lot about is benefit.

Segun: I've done a lot about recruiting people into research [00:21:43] in, in Africa, and there's a benefit sharing component. What we, what we have done in Uganda is that if you have high blood pressure, we have medication. We refer you to, uh, the clinic that is under our own control.

Segun: So we support you with your diabetes, support you with your high blood pressure or whatever thing that you have. If we cannot take care of you, that is where we now refer you to either to a doctor or a general, uh, general hospital. This is [00:25:00] really very important that there's a benefit. And also, uh, recently we've been working with, uh, some, uh, big pharmacy company, and we talk about benefit sharing.

Segun: Uh, for example, if we done some study, uh, we find some drug and med-medication, and the, the company had make millions of, of USD. So what come back to the community? So now we talk about, okay, can you now build an hospital here in this, uh, village? So we have to think about an appropriate benefit sharing also for the Black community in the UK.

Sharon Jones: Thank you. And I know, Christella, you touched upon some of those similar points that Segun made there. What does meaningful community engagement look like for you?

Christella: The benefit sharing is so important because we have to understand there is a problem, first and foremost, okay? And we have to understand the impact of that problem.

Christella: We have to bring solutions for that problem, but we also need to show those benefits in these communities that we're actually trying to engage with. And for me, when I'm talking about engagement, I'm really looking at co-designing, you know, not just consulting and telling them what to do, but the real difference is between being able to actually co-design the studies around Black people, so you can understand the nuances within the, the communities.

Christella: So understanding how to actually engage with these communities is, is really important And I think it's also being honest about the limitations that we have, that we've seen in the past.

Christella: You know? It's not about creating engagement which says you are the knight in shining armour and, and you're here to, you know, put a magic wand and [00:24:00] make everything okay. It's literally being honest about, you know, the preconceptions that people have. You know, what you're trying to achieve in the community, that you're actually trying to benefit the community.

Christella: It's important that those who are creating these studies don't go into a room and assume how these communities work. It's really about understanding the experience of Black people and letting them be experts of their own experience, using that to then find ways to better engage with, with communities.

Sharon Jones: Thank you. And Hazel, is there anything you would like to add?

Hazel: I think Cristella and Segun have hit the nail completely on the head. I think co-design is so important when it comes to engaging with the Black community. And I also think that [00:24:49] when it comes to research, it shouldn't just be about the research.

Hazel: It should be about, like, essentially giving back to the community as well. So e- exactly what Segun and Cristella were saying. So if we're talking about we need to do questionnaires or giving samples, the community, whoever is, whoever this research is for, should be able to [00:28:30] see results from this. It shouldn't just be a couple of years down the line they still don't know what is coming from this research.

Hazel: Because sometimes we do research and people don't understand what's happened to, to this research, and sometimes that is off-putting to people.

Sharon Jones: Thanks, Hazel, and we're gonna hear again from Mica, who captures that idea so powerfully

Mica (Clip): The research isn't for the NHS, it isn't for any medical institution, it's not for the government. It's for our community. We're at the heart of that research, and, like, we've got a chance to do something about it, and if you're not gonna put yourself out there, then who else is going to?

Sharon Jones: So, Segun, how can we ensure the future of healthcare innovations benefit everybody and they don't deepen health inequalities?

Segun: I would say that, so what is the benefit of, uh, innovation, if it does not benefit everyone, particularly people that need it the most? Uh, give an example, maybe Hazel will know a lot about this.

Segun: So now we have a sickle cell gene therapy. Of course, a few people have benefited, so this probably costs about, uh, millions of USD for one person. This is a great innovation, but who can benefit from it? It's too expensive. No-nobody's able to afford that. So we need to get a point where, so the so-called innovation can get to the right people, people that actually need it, and it's actually cost-effective.

Segun: In my own, uh, domain of work, we're trying to develop a new, uh, gene-genomic test or genetic risk score. So what we have seen from the data that is currently available is that, you know, when you develop this, the score from one particular population, it doesn't transfer to other population. So it-- the genetic testing, uh, is a great innovation, but it doesn't, it doesn't really do well in the, in the Black community.

Segun: So I think we should have to think much more at the beginning of innovation, uh, whether who is this innovation being prepared for? Who is going to benefit from this innovation? If innovation is not gonna, uh, benefit people that need it most, it doesn't really make any sense.

Sharon Jones: That's a good point. And Christella, you also had an example of what happens when communities are not adequately represented in research.

Christella: Yeah. So recently, um, in the NHS, they've started to, um, test for [00:27:45] a specific enzyme, which is, which is found in the Black community, um, for cancer patients going through chemotherapy. Originally, there were four enzyme that they tested for, um, in the genes, and they found that there's actually a fifth one which affects Black people within the community.

Christella: And it's so important that this happened because Black patients were having, you know, severe side effects to the chemotherapy, and some patients unfortunately passed away due to this particular enzyme. So understanding that our genes do have variants in it and some, as Segun said, some things which work in one community will not always work, um, in a different community.

Christella: So now before anyone undergoes a chemotherapy, the cancer patients across England undergo genetic testing, which can then lead into a change of treatment and reduce adverse, um, side effects for the chemo. Now that the NHS can test for this, it's gonna bring better outcomes to those in the Black community going through chemotherapy.

Christella: We all know chemotherapy is hard enough to go through, so making it a little bit better for those in our community that are going through it is so important, and that's why we need to be part of this research, 'cause without us, they won't know what's best for us.

Sharon Jones: Thank you for sharing that. And if you'd like to understand more about equity, please listen to our Explainer podcast, What Is Equity?

Sharon Jones: So let's hear from Mary with a message she'd like listeners to leave with today.

Mary (Clip): Thinking about my experiences, I would love listeners to take away the fact that engaging in research is bigger than you. It shapes your community, and it shapes the lives of the children coming in the future. Black communities, we need to know our baseline.

Mary (Clip): We need to know where we are starting. It's bigger than us. My engagement helps the granddaughter I don't have, and that's what I need people to know.

Sharon Jones: And given what Mary said, I'd like to ask you all, what message would you [00:29:34] like to leave for listeners who are interested in learning about research? I'll come to Christella first .

Christella: I think first of all, we have to acknowledge that the questions and the hesitations within the community are very valid, and we have to understand that this makes sense given the history of research.

Christella: But I would love listeners to be left with the knowledge that history shouldn't be the final word of our relationship with research. We ask the hard questions that we need to ask and invite those who need to also benefit from this research. And like Mary said, "I'm helping my grandchild that I don't even have yet."

Christella: And I think that's how we need to look at it. It's not so much just about us, but it's the future generation. It's about having better outcomes for each and every one of us, and that includes the Black community. So help shape further research, and medicine will actually benefit us in the future.

Sharon Jones: Hazel, what message would you like to leave listeners today?

Hazel: I think going into research can sometimes be hard. However, I do think research is incredibly important, [00:31:14] especially for the younger generation.

Hazel: So I do think that we should get involved.

Sharon Jones: Thank you. And Segun?

Segun: Yeah, I would like to, uh, recall what, uh, Christella was saying, uh, particularly saying that for everybody, uh, listening to me right now, if you are invited to participate in the research, please participate, you know.

Segun: Ask the right question, "What is the research for?" And, uh, how does it benefit you? Maybe not you directly, maybe your children or maybe your grandchildren. Everyone should remember that, uh, so research is ultimately for the people, for better healthcare.

Segun: So our contribution really matter. So you're contributing your sample really matter and can change, uh, somebody's life, can change generation. Every participant has something valuable, which is really key. So I would encourage all the listener to participate in research if you are invited.

Segun: Thank you.

Sharon Jones: I think that's a very salient point. We'll wrap up there. We've covered a lot today, from trust to participation and what is needed to change to ensure that healthcare is for everyone. A huge thank you to our guests, Christella, Segun, and Hazel, for joining me today as we discussed how Black communities are being served in health research.

Sharon Jones: If you enjoyed this episode and you'd like to hear more, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. I've been your host, Sharon Jones, and Behind the Jeans is produced by Deanna Barac, Sophie McLachlan, Katie Revell, Adam Wavy, and Patrick Wallace at Bespoken Media.

Sharon Jones: Thank you for listening.

In this explainer episode, we’ve asked Sasha Henriques, Director of Equity Assurance at Genomics England, to explain what we mean by the word equity in healthcare and genomics.

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, let us know on podcast@genomicsengland.co.uk.

You can download the transcript or read it below.

Florence: What do we mean by the word equity? My name is Florence Cornish, and today I'm joined by Sasha Henriques, who is Director of Aquity assurance here at Genomics England, and also has a PhD specifically looking at social justice in genomics. And Sasha is here with us today to tell us much more about the topic. 

So Sasha, I think with this topic, when it comes to discussing equity in healthcare, a good place to start might be by acknowledging that not everyone has the same experience with accessing healthcare or the same outcomes even when they do access it.  

Could you maybe tell us a bit more about why that is and what factors are at play there? 

Sasha: Hi, Florence. Thanks. It's a really interesting question because it's a really big problem. So, the reasons that we don't have access to the same things can have multiple different ways that we're affected, from where we're born, to the schools that we go to, to the education that we have access to. Lots of those things are outside of our control, and they're determined by the political landscape that we're born into, whether we're born in a rich country or a poor country, or a rich part of the country or a poorer part of the country. 

So those are kind of the structural things that might make things different. So, when we come to access healthcare, there might be different healthcare that's available to us. We might be able to negotiate the system differently because of what we understand about how healthcare works and what's available to us. 

And then there might be personal things about us that make those things more challenging, so the abilities that we have or don't have, both kind of the ways that we learn, the ways that we hear, the ways that we see. All of those things kind of change our access, so the way the system treats us, but also how we show up in the system are all things that can affect us when we come to engage with healthcare. 

Florence: And obviously, the topic of this podcast is equity, and  we hear this word equity a lot, especially in conversations around healthcare and genomics. But could you explain for any listeners who maybe aren't quite sure what exactly equity actually means?  

Sasha: Yeah. So I think lots of times people hear equity, and they think it's just about fairness, and it's just about treating everybody the same way. 

But what equity does is that conversation, that question that you asked me about, like, why do people experience healthcare different, there are all sorts of places in our lives where we will have different access, different benefits, different ways that we can participate.  

And what equity says is that because we're all different in those different ways and we have different needs, different ways that we're discriminated against, and different ways that we're privileged, what equity means is how do we design a system, how do we offer something or do something that enables everyone to have the same outcome of that benefit? 

So for example, you could make a research leaflet really easy for everybody to access. And what that would mean is that everybody gains more access to that information. But if you are discriminated against because of the way that you read information or the way that you access information, that's not really helped you. 

So it's helped everybody, so we can move everybody along, and that's kind of what we would call equality. But actually, you don't all get the same outcome at the end. And what equity means is that we understand the different needs that people have so that when we look at where everybody arrives to at the end, that's where we see the benefit, rather than just making a change that's the same for everybody.  

Florence: Can we dive a little bit deeper into that? That difference between equity and equality. Could you maybe explain a little bit more about that specifically?  

Sasha: Yeah. I guess there are different ways that people illustrate the difference between equality and equity. 

And so equality could mean, for instance that everybody needs to get to a certain position, like from position A to position B, and everybody needs a particular bike to get from position A to position B. And so equality would be that we give everybody the same bike. So we make sure that your bikes have the same speed, your bikes are the same make, that your bikes are as new as each other, so nobody is given a worse bike than the other to get from position A to position B. 

But it might be actually that you've given this bike to somebody who isn't able to ride a bike because they have a problem with their legs, or it might be that you've given a bike of everybody's bike is the same size, but some people are shorter than other people.  

And so while equality means kind of treating everybody the same, equity actually means that we take consideration of the fact that we may need to treat people differently, so that they can get the outcome. 

So everybody can make the journey, but not everybody's going to make the journey in the same way. And equity is about what do we do so that people can all experience things and benefits in the same way, rather than treating everybody the same way.  

Florence: Mm-hmm. And do you think there are any challenges in equity specifically to the field of genomics? 

Sasha: Yeah. So I think that's a really simple explanation that I gave between the difference of equality and equity, and genomics is a really interesting point to show why that's a really simplified version of thinking actually what equity means.

So when we think about genomics, there are a number of particular things about genomics and the history of genetics that make that equity conversation and the way that people's benefits and outcomes may be shaped really critical when we think about genetics. 

So one is, I spoke before about, you know, where you're born in the world can have a really big impact on what you're able to access and what you're not. And genetics is one of those things that kind of really changed the world but hasn't changed the world for everybody. And so the people who were studied, the people whose DNA was looked at, all of the things that give us the knowledge about how genetics should work, was largely done in only particular places in the world, so particular northern European countries, parts of the US, some of those studies have been done in Japan. 

So lots of the knowledge that we have around what genetics means for different groups and different people doesn't actually think about all of the people in the world. So when it comes to genetics, we're kind of using references and data that actually are already not equal with the people that we want to serve. 

So there's something like really embedded in the way that genetics works, that we're kind of already starting from an uneven landscape.  

And then genetics sits within healthcare, it sits within research, it sits within all these other places, which again, are affected by things like money and things like politics, political stability, geography, whether your country has legislation or policies for those things. So, I guess those are the kind of structural things that make genetics kind of different and more challenging when we think of those inequities that already exist. 

Florence: Yeah.  

Sasha: But then genetics itself is about finding information that, yes, is about you, but might also be information that we share with lots of other people, so people within our families, people within our populations. And so actually thinking about who has the rights over genetic information, how genetic information is shared, how the genetic information benefits everybody that it should, are other, like, really particular questions that come with genetics. 

So, there are all these different ways that the structure can build inequity into what we're thinking about genetics because of the history of where genetics has come from, but also the ways that the system kind of uses genetics, and the ways that genetics can be used against us. So I think it's really important, that conversation about equity in genetics, that it's not just about getting from place A to place B, it's about what is the road like? And what experience will you have? And when you get to the end of the road, what are people going to do with the information?  

Yeah. So actually, that really simple explanation that I gave can become really quite complicated when you think about something like genetics.  

Florence: And so you took on the role of director of equity assurance at Genomics England. Tell me a little bit more about that. What’s the purpose of this role? Do you have anything specific that you'd like to work towards or achieve?  

Sasha: So the reason that that role came about is because of some of those problems that I've mentioned, that you want organisations like Genomics England, research organisations, healthcare organisations, we often have missions and strategies that are about the benefit for society, that we do this work for the benefit of all, for the benefit of society. We want a world where everyone can benefit from genomic healthcare, for instance.  

These are really common kind of strategies, motivations, and intentions that organisations have, but they're so top level that actually what does that mean on a practical day-to-day?  

So my role really came about from Genomics England being really committed to the idea of equity and wanting to achieve it. But actually, in reality, how you make that happen in the different functions of an organisation can be really quite tricky. 

So how do we think about equity when we think about the science, when we think about the research, when we think about the data, when we think about recruitment, when we think about someone's experience of being part of research? There are equity questions in all of those places.  

Florence: Mm-hmm  

Sasha: Importantly, the thing that I want to achieve is to really appreciate the fact that everyone thinks that this is important, and give them some of the skills so they can think about what kind of dealing with inequity in their area kind of means.

But also kind of importantly, what the role also means is, like, there's equity and also there's assurance. So one of the things that doesn't quite always get attached to sometimes these conversations about equity, is that actually you can measure those things.  

So you can measure patients' experience. You can measure whether there was a benefit. You can measure whether there was a change in clinical outcome. 

So again, kind of using that example of the people on the bike, we can change things to meet people's needs, but actually we need to then kind of measure the times at the end of the race to see whether actually we improved the times for people now that we've made those adjustments. So that's what the equity and the assurance means, right? 

So the equity is kind of putting things in the system or in the design that we want to have the impact of fairness, but the assurance is, and how am I monitoring and measuring that so that I can say, "Well, actually, that was a successful change. I would do that again, or I wouldn't do that again." 

Florence: Well, I think we'll finish there, but that was such an interesting conversation, Sasha, thank you so much for coming on and, and taking the time to talk to us.  

Sasha: No problem. Thank you.  

Florence: If you want to hear more Explain episodes like this, you can find them on our website at www.genomicsengland.co.uk or wherever you get your podcasts. 

Thank you for listening.