The Festival of Genomics and Biodata is just around the corner, and we’ve had the opportunity to sit down with some of our expert speakers to get a sneak peek into what they’ll be discussing, and why they think you should come along to the event.
In today’s interview, we speak to Jason Vassy (Associate Professor and Director – Genomes2Veterans Research Program, Harvard Medical School) about how the Million Veteran Program is leveraging large-scale genomic and clinical data to build a “genomics-enabled learning health system.”
Register for the Festival of Genomics and Biodata here.
Please note transcript has been edited for brevity and clarity.
FLG: Hi everybody. Today, we’re joined by Jason Vassy from the Genomes2Veterans Research Program at Harvard Medical School. Jason will be joining us next month in Boston for the Festival of Genomics and Biodata, and ahead of his talk, we’ve got a little bit of time today to have a chat about his work, and I’m really excited to hear about it. So Jason, could you introduce yourself to the audience and tell us about your background and what it is that you work on?
Jason Vassy: Sure, well, thank you for this opportunity. I am a primary care provider trained in internal medicine, so I do primary care for adult patients. I’m also an Associate Professor of Medicine at Harvard Medical School, and my clinical practice is at the VA Boston healthcare system, part of the Veterans Healthcare System here in the United States. My background is as a generalist, I am interested in, generally, many of the things that cause health or disease for my patients. And in my training, certainly, we learn about coaching our patients on how to eat better, exercise more, stop smoking. But I was struck by some of the patterns; there were some people who were overweight, and some of those got diabetes more readily than others, or some individuals who might have a lifetime [history] of smoking but never get lung cancer, whereas those who never smoke might get lung cancer. So, it got me very interested in how genetics might explain some of those patterns of disease I see in my patients, which has led to my research career for the last 15 years, looking at how genetics or genomics might pick up some of these patterns of disease that we primary care providers otherwise are not very well trained to pick up. Some of my research tries to bring genetics and genomics to the point of care, specifically in primary care kind of settings.
FLG: It must be so striking seeing that as a clinical care practitioner, seeing those patterns, and it must be such a unique perspective to have seen it from both sides, in the clinic and in the research. Now, your talk at the Festival of Genomics is going to focus on using data specifically from the Million Veteran Program in healthcare. Could you tell us a little bit about what the Million Veteran Program is?
Jason Vassy: The Million Veteran Program is really a landmark achievement of research in the VA system here. So we, in the last year and a half, celebrated enrollment of our 1,000,000th participant. These are veterans who receive health care in our VA system, which is a nationwide system that currently cares for more than 9 million veterans in every US state and territory. And these veterans, these patients, these participants, have continued their service to biomedical science, in a way, to the greater community, in voluntarily consenting for the research use of their clinical data that we have in our electronic medical records here at the VA, in addition to providing responses to surveys about family history, diet, exercise, lifestyle, military exposures and a DNA specimen. So, because of that, we now have genetic data on almost a million veterans and we can now perform pretty impressive discovery for the underpinnings of genetic health and disease by analysing the genetic data, with the survey data, with the electronic health record data, spanning 25 years. So, it really has become a biobank with an impressive ability to generate genomic discovery. It really has contributed not only to veteran research, but really global research in genomics.
FLG: And by its size alone, it sounds like it must be a really unique resource, but the fact it has that electronic healthcare record link as well, it must make it so valuable. What advantages does that have over other genetic research databases?
Jason Vassy: It really is. The VA was really a pioneer in developing electronic medical records, and so, like I said, this 25 years of EHR data on more than 20 million individuals now, 1 million of whom are in the Million Veteran Program, is really unparalleled, specifically for US-based health, but also for global health. The trillions plus data points that we have in terms of prescriptions, in terms of laboratory values, vital signs, health care conditions, really is unparalleled. It really has enabled a lot of discovery in this area.
FLG: Something that you will be mentioning in your talk is the concept of a ‘genomics-enabled learning health system’, and I think that sounds really intriguing. Could you elaborate on what that entails and why that could be such a game changer for health care?
Jason Vassy: You might get a few definitions, depending on who you ask, but one helpful definition, I think, is if you have a healthcare system linked to a biobank, like the National VA Health Care System is linked to the Million Veteran Program, that offers not only opportunity for discovery – enabling massive genome-wide association studies to identify novel genetic variants associated with, say, prostate cancer – but because it’s also a healthcare system that’s taking care of patients, those discoveries offer the opportunity to somehow translate that information back into clinical care. To actually improve the care that the patients in that healthcare system are receiving. So, not purely just for ‘discovery, publish a paper, put it on the shelf’, but to actually now use that information in a virtuous cycle of bringing it back to patient care, and ideally change the way we take care of patients, and ideally that improves their outcomes. There are some regulatory hurdles for this. There are some scientific hurdles for this. And so, the science of a learning healthcare system is overcoming some of those barriers and hurdles to really make sure that we’re delivering. We’re doing this in the service of improving the quality and the safety and the outcomes of the care we deliver.
FLG: It sounds really like it could be revolutionary, a really great way to integrate new things into healthcare for people. But you did mention there are a lot of hurdles. Do you think that you can overcome those hurdles and this sort of approach could become mainstream at any point in the near future?
Jason Vassy: What we mean by mainstream, I think is to be defined. But I think absolutely this is where the healthcare system should move. One example that I’ll talk about at the Festival of Genomics is a prostate cancer study we’re doing. In the Million Veteran Program, we identified new genetic variants associated with prostate cancer. We were able to put together a prostate cancer risk model based on MVP data, based on these genetic variants, based on family history, just for good measure. We then took that model, went to other cohort studies outside the VA that have prostate cancer cases and controls, and showed that the model validated. We worked with a clinical laboratory to develop a clinical test to test this model, and we’re now bringing it back into patient care in the VA and doing a clinical trial where we’re identifying men who are eligible for prostate cancer screening, offering them the opportunity to get this novel genetic test and this score to help better risk stratify them for prostate cancer. That might help them make more tailored decisions for prostate cancer screening in a way that improves upon the current standard of care. So, in the process of doing that, we’ve started to overcome some of those hurdles that exist. And I think other healthcare systems, including the VA, are doing this in other different disease areas and other avenues. I really do think this is an active area, so some of these challenges will be overcome by these projects that are starting to implement them and working out the kinks and figuring out how this really can improve care.
FLG: And, correct me if I’m wrong, but I believe that’s the ProGRESS study that you were discussing there? I believe you’re also discussing another study called ROAR at the Festival. Could you tell us a little bit about that study as well, and some of the key challenges that you’ve faced and some of the lessons that you’ve learned from that?
Jason Vassy: That’s right. I didn’t maybe say it at the top, but initially, the Million Veteran Program was really just designed purely as a biobank for discovery. It always had that eye towards, ‘we want to make discoveries that then go on to improve veteran health.’ But the initial concept wasn’t that MVP participants themselves would necessarily directly benefit from their participation in the research. So, like I said, they volunteer, they voluntarily consented to providing the DNA sample, survey results and their electronic health record data without any expectation that this would directly benefit their healthcare That got off the ground in in the very early 2010s, and a lot has changed about our understanding of genetic disease, research ethics and our understanding of the human genome and what it means for an individual’s disease risk. By the late 2010s, the Million Veteran Program was thinking, we’re actually identifying some variants in these individuals’ research data that might have implications for their health. What would it look like, at least in a small pilot, for us to start reaching back out to some of these participants and offer them the opportunity to learn about some of these potential disease risk-related results they might have in their research data. So, MVP ROAR was that first step towards returning results back to MVP participants.
We started small, specifically with the disease familial hypercholesterolemia. This is a disease that’s characterised by markedly high elevations of so-called bad cholesterol, LDL cholesterol. It runs in families in an autosomal dominant pattern, and these individuals really should be identified, because they need much more aggressive, intensive treatment for their LDL cholesterol levels to lower their risk of heart attacks. Many of these individuals, untreated, might have heart attacks early in their 40s or 50s, much earlier than the general population. It also has a benefit for their family members; if an individual is identified to carry a genetic variant associated with this disease, cascade testing in their family members should be considered because first grade family members have a 50/50, chance of also carrying the variant. So, when MVP realised that we might be identifying FH associated variants in our participants that they don’t know about clinically, we designed a study to model what it would look like to reach back out to these individuals. This wasn’t initially what they signed up for, but we thought we needed to start exploring how we might return these results responsibly. We learned a lot of lessons in doing that, many of which I’ll share at the Festival of Genomics, but overall, it was an incredibly rewarding experience, not only for the participants themselves, who are very grateful and very appreciative of learning this information, but we also learned a lot as a programme, and it helped us think about what next steps might be in this area, and how to bring that value to the point of care.
FLG: It is so important to remember that when people make these discoveries, it’s not just impacting that individual, it does impact their families. There’s such a far-reaching impact of studies like this and resources like this. Something I thought was so interesting that you mentioned there was that this wasn’t initially set up with the goal of actually impacting these people’s health care. It’s so altruistic, isn’t it? That people would just sign up and not expect anything in return. Was that complicated? Or did you find it was quite easy to get people sign up for that?
Jason Vassy: I can’t take credit for the Million Veteran Program, it has really been, since its conception, a partnership with veterans from the very beginning. Veterans as a population are exactly that – altruistic. Very service oriented, constantly thinking about, how can I give more of myself to help, help the community, help fellow Americans. It’s just kind of in their DNA, so to speak. And as a trusted partner, the VA had many discussions very early on. What would this look like? What would your concerns be? What would your hopes be? What would your preferences be on how to launch a programme with us? So, there was a lot of in the early days, before my time, the surveys, interviews, focus groups, really teasing out what veterans value in a programme like this. That trust is hard earned, and trust can be easily lost. The MVP, we really pride ourselves in constant communication, interaction, and engagement with veterans to make sure we are keeping their needs top of mind and that this really is a partnership with them. With ROAR, we wanted to think about, how do we turn this around and start delivering value back to the participants? Again, veterans were very much a part of that conversation. So, absolutely it’s a privilege to work with veterans for that very reason, they are a very altruistic population, and it’s just a privilege to work with them.
FLG: That word partnership, it’s so important that you’re doing this work with people, you’re not doing it for them, and assuming that you know what’s best, and that’s one of the most important things to remember, I suppose. What do you think people can take from the experiences and the successes of these studies, especially when it comes to integrating genomics into clinical care?
Jason Vassy: There are a lot of implementation opportunities that need to be worked out. And some of those will really be healthcare-system specific. At The Festival of Genomics, I’ll talk about some of those challenges unique to the VA. Some will be unique to the VA, and some will be generalizable. We’ve already talked about trust, and if you don’t have trust with your patient population, it might be a non-starter, or certainly not as effective as you might otherwise want.
There can be other challenges introduced by the particular EHR or informatics ecosystem at a given institution. The culture of an institution can be important. So, primary care providers and other clinicians are very busy. If there’s not some of that constituent buy in for a programme like this, it’ll also be difficult to implement, and myriad other numbers of challenges or considerations that need to be thought of prior to implementing a programme like this. There’s also the ‘so what’ question. There have been 1000s of discoveries in the Million Veteran Program data, but not all of those discoveries would we say ‘this is now ready for prime time’, to be brought to the point of care, as in primary care. For example, me and my colleagues are already swamped with the things we’re trying to achieve in an encounter with a given patient – their cancer screenings, their mental health screenings, the treatment of their chronic conditions – we can’t be then told 1000 different things that may have been found in their MVP data. So, there needs to be a little bit of prioritisation. That’s also a discussion. Some it is a partnership between clinicians, the healthcare system, the patients, participants themselves, about the results or some of the outcomes of a project like this that most align with the values of all of those constituents, and what would you do that information? Some of it’s interesting to know, but if it wouldn’t change what you do, it may not have as much utility as something like familial hypercholesterolemia.
FLG: It does sound like there are definitely complexities. And in your opinion, what is the most significant hurdle in bridging the gap between the research and the everyday clinical practice?
Jason Vassy: There are many. If you ask a lawyer, they might give you a different answer. If you ask an informatician, they might give you a different answer. But as a clinician, I would say it really is making use of that information easy at the point of care, and I think a lot of that hinges on the electronic health record systems that are set up to allow a busy clinician to receive the information with the patient in a readily digestible way that seems actionable, and you immediately know what the next step is. I’m speaking from the point of view of a primary care provider who is not an expert in genetics or genomics. They need to know enough to understand the result and what to do with it. Does that mean refer to a specialist, order another test? What is the ‘so what?’ What do I do with that information? That’s a pretty complex clinical workflow, but it needs to be just right to make it easy for the patients and doctors and nurses to use.. That’s my primary care provider centric response for at least one of the most significant implementation challenges.
FLG: And you mentioned there are challenges in every different area, the legal side, the scientific side, the clinical side, but are there any ethical considerations that need to be addressed in that space?
Jason Vassy: Yes. Some of these came up in some of our studies, in the research ethics space. Initially, as I said, these participants didn’t initially consent to receiving their individual genetic results. It’s not that they declined either, it’s just that the question was not asked when they initially enrolled in the programme. We could overcome that, by re-contacting these individuals, giving them a tiered, graduated amount of information consistent with their consent, giving them the option to not learn about the opportunity or move forward with it, so that we were able to navigate. Ethicists will also point to the concern that if you focus too much on some novel programmes like this, does that detract from some of the other activities that a health care system needs to be undertaking? Mental health care screenings, cancer screenings? So, there’s a question of balance and priority that becomes an ethical question, if you are really detracting from the health care that we already know should be taking place. Typically, I tend not to consider health care as a zero-sum game like this, but healthcare resources are finite, and as is clinician’s time. That’s another consideration
Certainly, there is at least the hypothesised concern about patient anxiety about results. I’m usually able to counter that concern by relying on trusted colleagues in the genetic counselling field. Genetic counsellors, this is their profession, to do that pre-test counselling before results are received, to help with some anticipatory guidance with the patient or participant, to really assess and make sure that consent is truly informed, that the person’s eyes are wide open about the potential risks, benefits, whether that individual might be prone to being anxious about the results. And is getting genetic results aligned with their values and preferences. So, I think there are ethical concerns that must be considered. I think none of them are barriers that cannot be overcome, though.
FLG: It does sound like there are a lot questions that need answered. But as you say, it sounds like perhaps they can be answered, and it’s not a pipe dream. It would be amazing not to have to consider prioritisation, it’d be great to just be able to do everything. But it’s such a great point that choices have to be made. But it does sound like it’s all very hopeful, and it leads me to my next question. What personally motivates you in this field, and what personally motivates your desire to see this research applied in healthcare?
Jason Vassy: I really feel like I’m in an exciting nexus of genetics and genomics. Here in Boston, we are at, I think, the epicentre of omics technology in the world. And with my other hat as a bread and butter primary care clinician, I’m able to be right at the centre of amazing discoveries coming down the pipeline, and there’s a burdened primary care system that doesn’t have enough time or resources, and we are trying to do our best by our patients. How can I help design the systems that will bring these potentially groundbreaking, maybe even lifesaving, discoveries to primary care where the rubber meets the road? And really make it easy, where possible, for my primary care colleagues and their patients to take advantage of these new discoveries in a way that is practical, implementable, sustainable. So, that I find an exciting challenge, that’s probably a career’s worth of projects and goals. I just find it very rewarding to be at that nexus. And then, as I mentioned, doing that work in the VA and working with the veteran population is just even more rewarding. On top of that, just such a service-oriented place and such a deserving population to work with.
FLG: Rewarding was the word that came into my head when you were talking about it.
Jason Vassy: Yeah, it really is.
FLG: And it’s hard to deny your point about Boston being the epicentre of this field! It brings me nicely onto the final question I have for you, which is, what are you most looking forward to about the Festival of Genomics and Biodata in Boston next month, and why would you encourage people to come along to the event?
Jason Vassy: I am looking forward to welcoming everybody to our city. I think in June the weather will be nice, hopefully you’ll get some time to go out and enjoy the city, let alone the Festival. I am really excited not only to share my experience and the work we’re doing here in the VA, but also interact with attendees who might be doing similar things in their institutions, and really having some fruitful conversations about how that might work. The Festival of Genomics, the breadth of the expertise of its attendees is one of the main draws. So, you’ll have individuals from data science, clinicians, laboratory scientists, industry, healthcare, business. It really could be this crucible for some really impactful conversations, networking, collaborating. The fruit of which would just then grow over time, long after people depart from Boston. That’s why I’m excited, certainly to share the work that we’re doing, and to hear about the work that others are doing too. It’s really an exciting event to take part in. I couldn’t be more pleased.
FLG: Well, I think you’ve sold it to the audience. Thank you so much for taking the time to speak to me today, and we’re really looking forward to seeing you next month in Boston.
Register for the Festival of Genomics and Biodata here.
