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Discussion Guide and Transcript

Episode Seven

Research Ethics Reimagined Episode Seven “Exploring the VA’s Million Veteran Program with Sumitra Muralidhar, PhD, and Dr. Jason Vassy, MD”

  • In this episode of PRIM&R's podcast, "Research Ethics Reimagined," we explore the Million Veteran Program (MVP), one of the world's largest research databases of genetic, clinical, lifestyle, and military exposure information. Our guests are Dr. Sumitra Muralidhar, Director of the VA's Million Veteran Program, and Dr. Jason L. Vassy, Director of the Genomes to Veterans Research Program. (Transcript available) Listen on Spotify | Listen on Apple| Listen on Amazon Discussion Questions
  • 1.) Research Infrastructure and Trust
  • The MVP has enrolled over one million veterans who have voluntarily shared their genetic and health information. What elements of the program's design have helped build and maintain participant trust?
  • Vassy describes the MVP as a "research platform built on participant trust and partnership." How does the program's approach to data security and participant engagement demonstrate this commitment?
2.) Diversity and Representation
  • The MVP includes one of the largest cohorts of Black participants in any research program worldwide. How might this level of diversity benefit research outcomes and healthcare delivery?
  • The study known as “Million Veteran Program Return of Actionable Results (MVP ROAR)” emphasizes returning research results to participants and their healthcare providers. What are the benefits and challenges of this approach to participant engagement?
3.) Research Ethics and Innovation
  • What lessons can other research programs learn from the MVP's approach to participant recruitment, data management, and research translation?
  • How might the MVP's model of integrating research with healthcare delivery influence future approaches to biobank development and management?
Key Terms and Acronyms
Biobank: A repository that stores biological samples and associated data for research purposes
Precision Medicine: Healthcare approach that considers individual variability in genes, environment, and lifestyle.
Million Veteran Program (MVP): A VA research program studying how genes, lifestyle, and military exposures affect health and illness.
MVP ROAR (Million Veteran Program Return of Actionable Results): A study examining the feasibility of returning medically actionable genetic results to MVP participants and their healthcare providers.
Additional Resources

Transcript

Transcript, Ep7: “Exploring the VA’s Million Veteran Program with Sumitra Muralidhar, PhD, and Dr. Jason Vassy, MD” Host: Ivy R. Tillman, EdD, CIP, Executive Director of PRIM&R Guests: Sumitra Muralidhar, PhD, and Dr. Jason Vassy, MD A transcript generator was used to help create written show transcript. Written transcript of podcast is approximate and not meant for attribution.
Ivy Tillman: Today, I'm very pleased to have Dr. Sumitra Muralidhar with us. Dr. Muralidhar, who goes by Suma, serves as Director of the U. S. Department of Veterans Affairs Million Veteran Program at the VHA Office of Research and Development, which, as we will explore today, is one of the world's largest databases of genetic, clinical, lifestyle, military experiences, and exposure data from more than one million veterans. As the programs director, she oversees the policy. Funding and implementation of data collection, secure storage and use of MVP data. She's also the director of the Veterans Affairs Department of Energy Joint Research Program. Suma served as the liaison of the VA's Office of Research and Development to the White House Precision Medicine Initiative under President Obama and continues to serve the VA in the federal inter-agency work groups on precision medicine. She received her PhD in molecular biology. from the University of Maryland and her Master's in Genetics from Bangalore University, India. We also have with us Dr. Jason Vassy, who serves as attending physician at the VA Boston Healthcare System. He is an MVP researcher and director of the Genomes to Veterans Research Program. He is also an associate professor of medicine in Harvard Medical School. The Genomes to Veterans Research Program, which is based at the VA Boston Healthcare System, conducts biomedical research to determine the role of genetic and genomic technologies in improving the care and health outcomes of veterans and other patients. Jason earned his M. D. degree from Washington University School of Medicine. Before completing an internal medicine residency at the University of Pennsylvania. So welcome Suma and Jason to our podcast. We are so happy to have you and to discuss the MVP programs. Sumitra Muralidhar: Well, thank you, Ivy. Thank you for the invitation. I'm really happy to be here. Jason Vassy: This is a real treat to be able to share some of the work we do. Ivy Tillman: I have background in having been with IRBs that were the affiliate IRBs for our local VAs. So, this means a lot to me, too. And I thank you for your time and the work you're doing. Many may view the VA solely as a health care provider for America's veterans, that is far from the case. While the VA provides more than 9 million veterans with a wide range of care, at more than 1, 200 health facilities across the United States, the VA does much, much more. From research on tuberculosis in the 1940s to today's developments in advanced robotic prosthetics, the Department of Veterans Affairs is one of the nation's leaders in health research. This research is what we're going to discuss today. First, I'd like to share some successes of VA research over the years. And I find these accomplishments quite fascinating. According to the VA's Office of Research and Development, VA research has contributed to many crucial advances in health care, including the development of microelectronics and robotics to create artificial limbs that look, feel, and work like natural arms and legs, the creation of the nicotine patch to help people stop smoking, the invention of the cardiac casemaker, the first successful liver transplant, the development of the CAT or CT scan, and the development of new drugs and treatments for diseases such as HIV, AIDS, diabetes, Alzheimer's, and osteoporosis. Today, we're going to learn about the VA's Million Veteran Program. As I understand it, the VA's Million Veteran Program is a national research program that looks at how genes, lifestyle, military experiences, and exposures affect health and wellness in veterans. For And, since launching in 2011, one million veterans and counting have joined the Million Veteran Program, making it the largest research effort at the VA to improve health care for veterans and one of the largest research programs in the world studying genes and health. So, in essence, it's a massive database of genetic, military exposure, lifestyle and health information of veterans. Which can be used to research how to prevent and treat illness of veterans and people throughout our country. So, I'd like to start with a simple question, which I'm sure has a complicated answer. How does this program work and what are the goals of the Million Veteran Program? Sumitra Muralidhar: It's a great question to start. I'm going to start off with your second question. You know, our overarching goal is really to help improve the health and wellbeing of our veterans by enabling personalized or precision healthcare approaches. And by that, I mean, rather than using a one size fits all, we take into consideration all the different factors that really account for our risks for different illnesses, as well as for wellbeing. That's, that could be genetic, it could be lifestyle, military experiences or exposures. And your health history and family history as well. To achieve this goal, we really set out with the specific objective of establishing this large database by enrolling over 1 million veterans and counting to contribute their health data, contribute a biospecimen, a blood sample, so we can generate all the genetic and other molecular information, complete surveys about their lifestyle, health, family history, health history. Because a lot of these things are not captured very well in the electronic health record. Although the VA has one of the best electronic health records that goes back over 30 years and very comprehensive. But the surveys kind of help to fill in the gaps that are in the healthcare records themselves. And so, we launched this back in 2011, and the program is essentially sending out invitational mails, emails. We do a lot of surround sound communications. Now we've evolved from the mail only to reaching out to veterans by different methods, social media, as well as paid advertisements to tell them about the program. And it's a voluntary national research program. And so, if they are invited, if they are willing to enroll, then they can enroll at one of our VA medical centers. We have about approximately 70 of those right now that are enrolling in person, or they can enroll online. The online portal was just established before the pandemic, fortunately. So, we actually leveraged that platform during the pandemic. So, they enroll, complete the informed consent and authorization, provide their blood specimen, surveys completed at home, we have several of them, and they give us access to their health records, and they agreed to be recontacted in the future. Ivy Tillman: Amazing. And, you know, in the intro, I mentioned just the number of veterans who have voluntarily participated in the study, and that's remarkable in and of itself. I'm sure we'll talk about that more, but from what we learned about the Million Veteran Program, the VA is working on mental health issues. Preventions and treatments for PTSD, depression, anxiety, and suicide, heart health, cancer, nutrition, diabetes, Alzheimer's, and more. But what do you think are some of the most significant accomplishments of the VA's Million Veteran Program over the last 13 years? Sumitra Muralidhar: Well, there are several of them. I'll get started and perhaps Jason can add to them, but I think one main accomplishment is that we have established a way that researchers can come to the data in a secure, central, scientific computing environment and access the data, conduct the analysis, that we provide all the tools and are able to take away the results to publish. So that's one significant achievement that has allowed the science to flourish. We have over 400 publications. They have come out of the program in all as in all various disease areas. They've been able to conduct some of the largest studies, for example, a study looking at genetic risk of PTSD in over 165,000 veterans, a study of anxiety, genetics of anxiety in over 200,000 veterans. So, conducting a genetic study and not only looking at how genetics contributes to risk, but also adding in other factors now like lifestyle and other nutrition and so on to this analysis in, it requires such large data sets. And so, we've been able to do this kind of research at scale because of what we've established here. Jason Vassy: I was, I was just going to weigh into there that, you know, one of the amazing features of MVP is we are uniquely positioned to study many of the health conditions that are unique or particular to veterans because of their various exposures, their military service, but also veterans are people. So, they also get cancers and heart disease and other conditions too that are really important for the rest of human health. And so, we are uniquely able to study diseases like PTSD that are particularly burdensome to the veteran population. And at the same time, study the common conditions that, that is just part of, of human health and disease. So, it really is kind of a twofer in that we're fulfilling our mission to veterans to really improve their health specifically, but really we think the entire scientific community benefits also. Ivy Tillman: Absolutely. Absolutely. So, really trying to understand like, what is the process for veterans enrolling in the program, you mentioned it earlier, Suma, that some, they actually can enroll online. What does that involve? And specifically in a study that we'll discuss later, Jason described this MVP program as a research platform that's built on participant trust and partnership. And for those who are familiar with PRIM&R, that's, you know, central to who we are and why we exist is to advance that trust in science and research. So, can you explain how this is important to participants and MVP? Sumitra Muralidhar: Yes. So even before we launched the program, we conducted focus groups and surveys of our veterans to really understand, you know, what is their attitude about genetic research? What are their major concerns? What are their expectations? And so on. And so, what stood out as a big concern is the privacy and security of their data that they will be donating. So, we built the entire program considering taking into consideration this concern that they had expressed. And so, from the point of collection, whether it's a blood tube where we collect the blood specimen or the survey data that we collect or the health record data we bring in, we do not use direct identifiers. You know, the data is coded. There's a barcode on the test tube that we collect the blood specimen in or there's the same code on a different code rather in on the survey form that we bring, collect surveys through and so on and so forth. So, this way we have at the back end a core group of staff that can actually link it back to the identity. But during the process of collection, it is coded. And similarly, when we provide the data to researchers, it's all coded. We remove all the direct identifiers, such as name, you know, social security number, the date, part of the date of birth. Those kinds of things are removed from the data set. So, researchers also see a coded data set. And so, we did this to ensure that we respect the wishes of our participants. Jason Vassy: And I'll add, as a researcher who then has access to MVP data and analyzes it to try to learn more about health and disease, knowing that there was already that, that foundation of trust and MVP has really tried to honor that trust by implementing these really state of the art privacy and security methods, I, as a researcher, know that I'm working in an infrastructure that is going to honor that trust. There are protections in place and that, you know, that I am now as, as a researcher who has access to the data, can continue that, that line of trustworthiness within that optimized for success to make sure that we maintain that trust and that we honor it. Ivy Tillman: And, you know, you're going to hear me probably say this word a lot, but model, because as we were researching and learning about this program, I just see this as a model for similar types of research programs, large scale, but also small scale. When you speak of, you know, the trust and actually getting, or having the conversations with the potential participants and understanding what their concerns are and then building your research program around that, I think is amazing, and a model that we should be using not just in this program, but throughout research. So, I thank you for that on behalf of the research ethics community. So, you mentioned a lifestyle survey, and can you describe the type of information that's collected and how that's helping researchers? You talked about it a little bit. Sumitra Muralidhar: Yes. So, a lot about the lifestyle, you know, exercise habits, how often they exercise, what types of exercise they do, nutrition, what kind of food intake, all that is converted to the value in terms of nutrition. And we have one of the largest nutrition database actually as part of MVP, over 400, 000 veterans completed that and that's available for research, sleep patterns, smoking, other substance use, you know, all of this is captured, health history, family history, and this is very important because again, then researchers are able to add these as components and pieces to their analyses and see how these factors interact with each other and how they impact health and wealth. Jason Vassy: And it's so important, even if you're doing a mostly genetic study, we like to say often that it's more your zip code instead of your genetic code that determines a lot of your risk for disease, and so without having that context about who is this particular, who are these, who's this population, what kind of lifestyle, exposures or other exposures are they seeing, in addition to any genetic susceptibility they might have, it's really important context. Ivy Tillman: So, staying along that line with genetic research. And in terms of thinking about a genetic research database, a gene is the basic unit of heredity and is made up of DNA. Genes may also contribute to our risk for disease, including common illnesses like heart disease, diabetes, and cancer. With that in mind, can you explain for our listeners more about the human genome? And what advantages does this massive database give researchers? Sumitra Muralidhar: So, I'll start with that and maybe Jason can continue. So, the human DNA has about 3 billion base pairs or letters that, together, you know, have different codes in them. And all these base pairs sort of amount to about 20,000 to 25,000 genes. And maybe there's a little bit more than that now. So, there's a lot of there are variations. There are some common variants and there are other more rare variants, you know, that contribute to illness and genetics may be only part of the risk for any disease that may not be, you know, there are some exceptions, but by and large, especially for chronic diseases, it's not just a single, variant, and it could be a combination of different variants coming together. So, what's more popular now is what's called a polygenic risk score, taking into account a number of variants that together could contribute to a certain percentage of the risk for an illness. And so, to study, you know, what is the genetic risk for any condition, you really need very large numbers of people with a particular condition. And an equal or even larger number of people without that. So, you can compare them in your analyses. And so traditionally what used to happen is that, you know, researchers would enroll maybe a few hundred or a few thousand even, participants in a genetic study, but that was not sufficient to really have the power, the statistical power to detect these genetic variants that could be contributing. And so, establishing a mega database like this, where if you're doing a study of blood lipids and the genetics, we had 300, 000 individuals as cases, and then we have the rest of it, like you know, the 700, 000 could be controlled. So, this massive amount of cases and controls is what this type of a database provides. So, you can detect these differences in genetics that could be associated with a condition. And beyond that, I think it's the diversity as well. So, you're, it's not just the numbers, you know, largely, primarily in genetic research, it's mostly people of European descent that have been studied previously. And so that may not apply across the board to people from all different ancestries, you know, races and ethnicities and gender. And so, creating a mega database like this now allows researchers to look at what's, you know, what's different and what specific populations, what type of risk specific populations may have for these illnesses. And in fact, in a number of our publications that have come out, we are beginning to uncover new genetic variants, specifically in veterans of African ancestry or in a Hispanic population. Ivy Tillman: Fascinating. So, Jason, could you walk us through, and Suma, could you walk us, walk us through. How do researchers get permission to use MVP? Jason Vassy: Sure, I'll start and then Suma can weigh in also. So, MVP data is accessible to VA investigators who are, you know, who have already been research credentialed. They've been approved to be researchers and to be able to access VA data, including MVP. There are additional trainings for the appropriate use of MVP data to make sure that we maintain that trust, that we continue to maintain the information security and privacy measures that are in place. And then with approval overseen by the MVP program with the relevant IRBs, with our research and development committees, locally, we are able to then apply or access MVP data with approval in a protected environment. So, we go to the data instead of bringing the data to us, we go into the MVP environment to analyze the data, for the questions that some of the pressing questions for veteran health. Sumitra Muralidhar: And I'll just add that, you know, we started small, we started, I mean, of course, the VA research program is an intramural research program, so we can only fund VA researchers. And we have a number of mechanisms already within the VA Office of Research and Development for VA researchers to apply for funding. So, MVP basically leverages what's already there within the VA research enterprise. So, researchers have to get funded, approved, and then go through all the processes that Jason mentioned. We more recently opened up VA researchers applying to external federal funding, like NIH funding or GOD funding, to be able to use the MVP data. Our ultimate goal is really to be able to make this data more broadly available to the research community. And towards that end, we're looking at a number of efforts right now, and one of them is the VA data commons, that's outside the VA firewall, if you will, it's actually through a contract with the University of Chicago. And here we will have a copy of de identified MVP data and where we can allow researchers from outside the VA to also access this data, but in the de identified manner. And so, we will be piloting that activity this current fiscal year. And this is more of where researchers can put in their requests. They don't actually touch the data per se. They can put in their requests for what kind of analysis they want to do. And the analysis is run behind the scenes by the analytical pipelines, and they get active results. So that's the model we're looking at for external researchers. Ivy Tillman: Oh, fascinating. And along that line, Suma, I believe you mentioned in our podcast planning call that this MVP program has a collaboration with the Department of Energy's Oak Ridge National Lab, analyzing thousands of health characteristics and tens of millions of genetic markers. Can you elaborate on that and share what possible advances might be coming from this collaboration? Sumitra Muralidhar: Sure. So, we established a partnership with the Department of Energy back in 2016. And the goal was really to leverage not only their supercomputing infrastructure that they have, but also their expertise in computer science. And so, a copy of the entire VA corporate data warehouse data and some limited MVP data are now at the Oak Ridge National Laboratory. They have the same security parameters as they do within the VA. And, all of the other processes are the same for how people obtain access, you know, permission to use the data and access the name. All of that is the same as it is within the VA. But here are what this interesting project was that we had access to their supercomputer, a couple of the supercomputers, and what we were able to do was take about 45 million genetic markers and about 2000 health characteristics, and all together, look at how they associate with one another using the supercomputers. Now, this would, this was like about 350 billion analyses. And this would typically take about eight to 10 years to complete. If you were going one disease at a time and looking at what, you know, markers are there and so on. So, this was the first time we were doing it there. It did take us about a couple of years, but a lot less time. And what came out were a lot of interesting confirmations of existing associations and a lot of new associations as well, including some opportunities for drug repurposing, you know, genetics-based identification of potential targets for various chronic diseases, including diabetes, prostate cancer, and others. We're looking at these potential targets, new targets for treatment that could be acted upon by medications that are already approved by FDA. Of course, they need to go through validation and clinical trials, et cetera, all of that. But here are lots of new opportunities for drug repurposing and finding new treatments for chronic diseases. A couple of other things that have come out of there is the partnership on a project on suicide risk prediction. I mean, sadly, as you know, the rate of suicide in veterans is much higher than in the civilian population. And the VA has an algorithm called the reach vet that it uses to estimate suicide risk. So, working with our DOE scientists in this environment, we were able to identify additional factors that could affect suicide risk. And in fact, these are now in the process of being incorporated into new versions of the restrat, which will be coming out in the next year or two. So, this is a significant contribution to the field, this partnership. Ivy Tillman: Directly impacting the lives of veterans. Jason Vassy: And I'll say, you know, I, as a primary care provider in the VA, patients who have a certain threshold of REACH VET score, I am notified about that and we put additional clinical protective measures in place to ensure the safety of that veteran. So, this is a real-world impact. This is how we practice medicine in the VA and MVP and DOE is helping to shape that. Ivy Tillman: Excellent model. So, we mentioned earlier, one of you did, when we began, just about the footprint of this MVP program and the number of VA facilities currently participating. It looks like all the regions of the country are covered and veterans are also able to join online as we discussed. Can you tell me more about just how large the program is and the footprint in particular in the facilities participating. Sumitra Muralidhar: So, there are roughly about 70 VA medical centers that actually have staff boots on the ground that actually interact with veterans. And, you know, take them through the informed consent process and enroll them, get the blood specimen on site. And they also reach out to over a hundred community-based outpatient clinics. So, the footprint itself is much larger than the major VA medical centers. And there are, you know, gaps somewhere in the Midwest and some of the rural areas. We haven't actually expanded in person. But having the online footprint has helped, you know, so that veterans anywhere can enroll. The issue there, of course, is getting a blood specimen. And so, as I mentioned earlier, you know, this sort of, we just launched this portal before the pandemic. And so, we had to come up with some innovative ways of getting a blood specimen, and we piloted an at home blood collection kit called the Tassel Plus. It really, you know, it's a small amount of blood, but you can still get enough DNA from this biospecimen to do some baseline genetics. And so, that has helped, that has expanded, and we are looking in the future how we can, you know, take MVP to all veterans. You know, it may be other ways of taking the program around the country in different places where we don't have a physical presence. Yeah, but the footprint is pretty large and going forward because we're going to be focusing on enhancing the diversity of the population. And, you know, any underrepresented communities, we want to enhance that, we are looking at how we can come up with innovative ways to increase this footprint even more. Jason Vassy: So, is it safe to say that we have veterans from every state and territory in the program? Sumitra Muralidhar: Actually, we have veterans from every state. That we have checked. Yes. Jason Vassy: Oh, wow. Yeah. It's remarkable. Ivy Tillman: That is. It is. And along the lines, like you mentioned, Suma, about increasing diversity, once again, using that word model, we learned that more than 100,000 women are a part of MVP and over 25 percent of participants in MVP represent minority racial and ethnic backgrounds, a very diverse racial background. We understand that MVP also has the largest cohort of black participants of any research program in the world. Number one, how did NVP achieve that? Number two, how does that level of diversity really help researchers? And, you know, how are you looking to continue that, to diversify the data set? A lot of questions right there. If you need me to break it down, I will. Sumitra Muralidhar: No, I think so. The thing is that we did not really have any targeted mechanisms up to a million. Getting to a million, it was all comers. And so, it just happened that we aligned with the demographic representation of veterans that seek care at the VHA. And that's how we ended up with 10 percent of veterans in VHA are women. And we ended up with roughly the same percent of women in MVP. But we did much better on veterans of African descent. You know, it's about 14 percent in the VHA. We have almost 18%. And, that again just happened, you know, it really just using all the different methods we have for reaching out to veterans and telling them about the program. And so, it's over, if you think about that, it's over 180,000 Blacks that are in MVP. And that is why we have been able to make some of these new discoveries of new genetic markers that are specific to veterans of African descent for PTSD, for anxiety, for depression. And for glaucoma, we have a polygenic risk score that's specific to the Hispanic population. So, in many of these studies that we're coming up with now, where genetic markers that are specific to a population, and that's how you know, that's our goal. We want this to be, you know, sort of, it's equitable. Every veteran should really gain from what we do with MVP. And we want to be able to provide that equitable health care in the future. So that is, that's how it came about. Now going beyond a million, if you look at some of the other populations, like Native Americans, Pacific Islanders, Asian Americans, now those are in very small percentages in the VA, as well as in MVP. And so, we will be looking at enhancing those populations as well. We've been conducting some insight sessions with veterans from different backgrounds to better understand how, you know, what, what would resonate with them? How do they want us to reach out to them? You know, what would make sense for them? And we will build our recruitment packages for those populations based on that. Ivy Tillman: Amazing. So, I'm going to shift gears a little bit and ask you, Jason, about a study that you co-wrote, and it was entitled Design and Pilot Results from the, Million Veteran Program Return of Actionable Results Study. It's called MVP ROAR. According to your abstract, you state, as a mega biobank linked to a national healthcare system, the MVP can directly improve healthcare of participants. To determine the feasibility and outcomes of returning medically actionable genetic results to MVP participants, the program launched this MVP ROAR study. And your conclusion states, while underscoring the importance of clinical confirmation of research results, the pilot phase of MVP ROAR marks a turning point in MVP and demonstrates the feasibility of returning genetic results to participants and their providers. This is so important. And so, I'm getting to my question. What do you mean when you say it's a turning point? And can you share more about your conclusions? Jason Vassy: Well, before I kind of discuss the turning point issue, I think it's important for the listeners to understand the difference between the N equals a million and the N equals one. So, you know, as Suma has talked a lot about how it really takes a biobank of this size where you have hundreds of thousands of cases and hundreds of thousands of controls to make genetic discovery. And when you do that, it's okay if 900 or, I'm going to get the math wrong, 99,999 are right and one of them is a little off because you'll still identify that important genetic pattern and make discovery about how genetics is associated with disease. It's a whole different story within you're talking about N of one patient in front of you or the participant in this case, and you're going to give that person his or her result, so to speak, and make that that might have importance for their health. The kind of standard of evidence that you need to make that call for one individual is much higher, should be much more stringent than when you're making scientific discovery claims in a biobank of a million of a million individuals. So, MVP was a research enterprise built on trust, but it really initially was for that discovery. We then, a lot has changed since 2010, 2011, when the program got off the ground. And so, the scientific community was starting to learn more about the genetic underpinnings of health and disease. We realize that there are some things that are thought to be medically actionable and important that if identified in research data should be considered for return back to participants. But for all the reasons I just mentioned, it's not a given that you could just take those research data off the shelf without critically examining them and then just giving them back wholesale to participants. So, MVP Roar was really that first pilot experience in what would it look like to identify a small subset of genetic results that we think are medically actionable and get them back into the hands of the participants and their health care providers. I think that's particularly important for an institution like the VA because yes, we're a research enterprise and at the same time, we are their doctors and their health care system. So, we have kind of that dual role. So, we started small with one common genetic disease called familial hypercholesterolemia. These individuals have very high levels of cholesterol that runs in the family and can lead to premature heart attacks in your thirties or forties, and premature death as a result. And there are some individuals who have this disease, but kind of go under the radar. You know, their doctors are checking their cholesterol. It's noted to be high. Maybe they put them on a cholesterol medication, but they don't take it as seriously as maybe a healthcare provider might if they knew it was actually a genetic disease, this particular genetic disease called familial hypercholesterolemia. So, MVP Roar was designed around reaching back out to individuals whose MVP research data suggested they might have this condition and getting those results clinically confirmed in a clinical lab. And if confirmed, then getting them connected to appropriate care. So, a turning point in the MVP program in that it was one of the first times we reached back out to participants to give them individual level results. But, you know, not really a turning point in the sense that it's still kind of a continuation of that relationship of trust. I think the veteran and, you know, we were trying to honor that trust in every step of the way, doing something we think is in their best interest. Ivy Tillman: Wow. And so, once again, that model statement in question, do you think that this process of sharing the data back with the participants and their healthcare provider could be incorporated in other research models outside of the VA? Jason Vassy: I do, at least certain aspects of it. We are, we have that dual privilege of being researchers and clinicians. So, other biobanks that are linked to healthcare systems could do similarly. We have the blessing and the challenge of scale. We are at national scale. And so that is, it is such an awesome environment to work in. And it's also pretty complicated when you then think about trying to initiate a return of results program at a national scale. But yeah, I think there's, there's certainly lessons that can be drawn from our experience so far. Ivy Tillman: Absolutely. Well, last question for you both. Next year, I understand it's the 100th anniversary of VA research. Which is remarkable. That's a remarkable milestone. Thinking back, are there elements of VA's research that kind of stand out to you as some of the most important advances for veterans healthcare and more broadly, healthcare in general? Sumitra Muralidhar: That's a great question. And yeah, we're really excited to be, to be around for a hundred years. To be celebrating it next year, you know, you mentioned some of those earlier when you introduced the program. The first liver transplant, you know, the nicotine patch, there are others like the cardiac pacemaker, aspirin to prevent heart attack, that trial was done at the VA, the shingles vaccine. There are so many of these that actually came out of the VA but are actually applicable to the larger community. And I think in the field of prosthetics, research and development, the VA really leads the nation as there's a lot that's come out again in terms of robotic arms and functionalities, the new functionalities that have been developed and that's going to continue. And I think now with this new wave of precision medicine, we have a precision oncology program within the VA, increasing lung cancer screening, prostate cancer, germline genetics. Again, they're doing this at the clinical level to estimate who might be at a higher risk for prostate cancer and other cancers as well. And in just precision medicine in general, precision mental health. And so, I think going forward, there will be more such efforts that come out of the VA that will inform the larger community. And, I'll actually look to Jason to tell us a little bit about his recently funded study from the NHGRI, which looks at this implement a genomic medicine implementation. Jason Vassy: I think, like Suma was saying, I think maybe that's the kind of the next generation of some of this line of work is increasingly moving some of these discoveries into the clinic. So, two initiatives I'm involved in, one VA is participating in a NIH funded consortium of other learning healthcare systems to come together, identify common challenges and opportunities, to create so called genomics enabled learning healthcare systems. How can we use genetic and genomic data available for our patients to improve the care that we deliver and the outcomes of that care. Another example is using a prostate cancer prediction model that we have built using MVP data validated in external data sets. And then developed a clinical test to be able to measure that risk model. We're now bringing that back to the VA to launch a randomized controlled trial of prostate cancer screening. Either by usual care, as is currently practiced, or as informed by this new genetic marker and this risk score. And so, we can then follow to see which approach to prostate cancer screening can identify the people who don't need prostate cancer, maybe, or who don't need screening, perhaps, and therefore don't have to undergo unnecessary biopsies and tests. And those men who are really at high risk of prostate cancer and really do need to be screened and identified early, to make sure that we detect disease early or prevent disease. So, I think that's what I'm excited about, bringing the N of a million to some of these N of ones in the clinic. Ivy Tillman: Amazing, amazing work that's done at the VA. And I just want to again, just reiterate our thanks here at PRIM&R for the work you're doing and for sharing your time with us today.