 Carlos, we're going to start with Jim's presentation and we'll make it obvious when your presentation is up and then go through your slides. So thanks. That's a little loud, isn't it? Let me lower this. It's been a good discussion. We're turning now to the issue of minority enrollment and they've asked us to talk from NC Genes because we've had some experience with that in the course of the last three or four years. And the big lesson that I've really learned is that just having a study that's embedded perhaps in a population that is fairly rich in minorities still doesn't ensure robust minority participation. So we have to learn some lessons about how to target things and how to enrich that. I don't think I need to belabor why minority recruitment and the sustenance of participation is important, but I do want to just articulate both the social and the scientific reasons for it. One is simply social justice. In the realm of research, we have to ensure that what we learn is broadly applicable to the entire population. Medicine has certainly had a long history of not doing that and we don't want genetics to follow in the same footsteps. In the clinical realm, we also need to ensure that advances aren't just left to kind of make their own way and trickle down into other populations with all the research being in one particular population. And for their excellent scientific reasons as well that we need to ensure robust minority participation, this is data that Jonathan Berg has pulled from NC Genes and put together really nicely showing in a way, if you will, an ability to quantify the disparities that exist in variants. If you look at the average Caucasian individual that should read 110,000 variants in the typical exome, I'm sorry, in the African American, with about 90,000 in the typical Caucasian individual. So right off the bat, we have a significantly large amount of work to do that's additional, that's extra in an individual from minority population. This has obvious implications for interpreting the results of any given individual from the African American population, but it also has implications for all of us, right? Because understanding the variation in any one particular group is going to have an impact on our ability to interpret those variants across all groups. And therefore will benefit the entire field. We also have to remember, of course, that the meaning of minority is going to differ in different contexts. Now in CSER as a whole, we've seen about 5,000 individuals enrolled, and we're not doing horribly, but we could be doing better. What we see is slightly less than the national average for African Americans, substantially less than the 16, 17 percent national average for the Hispanic population, but this is a little deceptive in that because those numbers are lower and because the variants are higher in the populations, especially African American, we're going to need better recruitment and better studying of these populations to really interpret the variation that occurs. To NC Genes, the study centered at the University of North Carolina is embedded in a population that is about 64 percent white and non-Hispanic, about 22 percent African American, about 9 percent Hispanic. If we've tried to target both African American population and Hispanic populations, but the point being that those are different populations and one may need to make, have different strategies in order to do that. The major key to any success we've had in the African American recruitment has been through our partnership with a cardiology clinic in the eastern part of the state located in Greenville, North Carolina, a little bit more than a half a million people, and there's about a third of the individuals in Greenville or African American. We've teamed up with this cardiology clinic that's a large clinic with two advanced heart failure cardiologists whom we've worked with mostly. This is Hassan al-Hassani, who's been our major partner. They see about 6,500 patients a year, and they have plans to expand into a couple other counties that also have very robust African American and to a lesser extent Hispanic populations. Their present mix is 60 percent African American with few Hispanics. To target the Hispanic population, we took a different approach. One is the obvious necessary measure of having a scheduler, someone who's going to contact folks on the phone who's fluent in Spanish, and I think it helped. I don't have data specifically addressing this, that she's a native speaker. We have translated written materials that are available for enrollment and education, and ready access to the interpreter for all the visits including enrollment, return of results of visits, and phone calls. The phone surveys themselves are via the native speaker that we hired for that purpose. If you look at the cascade, that is what has happened to the eligible body of people that we have tried to enroll, and then the various steps along the way in which we see either an enrichment or a loss of particular populations, it's quite informative. Again, Jonathan Berg has put these data together. We see that there's a paucity, a deficit in the enrollment of African Americans and a commensurate increase in the non-enrolled individuals who are African American. We don't have big enough numbers and haven't really seen a difference in the Hispanic population. If you look at where that non-enrollment seemed to occur, because it could occur anywhere from they never answered your call in the first place to they just dropped out somewhere along the way, the most robust numbers are down here where we see that there's an enrichment of individuals who are not enrolled in the overtly declined population and an enrichment in those who have had incomplete visits. That is, they made it to one visit, but they canceled, they didn't show up, they've tried to be rescheduled and we haven't been able to do that. These in a way are people who have voted with their feet and said, you know, we're not going to really complete the study. Looked at another way, we can say that 18 of 62 visit canceled entries are African American where they actually canceled visits, 34 of 64 of the no show visits are African American. So although there are 23 percent African Americans within the nominees, the pool from which we have derived our subjects, they accounted for many more of the missed visits. That's in contrast to our experience in the clinic in eastern North Carolina where we've had 59 nominees, 88 percent of whom are African American, and we've had an enrollment success there of 50 percent consistent with success rates for other populations at other centers in NC genes. Among non-Vitant nominees, we've had a much more dismal success rate, 28 percent with African Americans. Suggesting the importance of having an outreach clinic and reflects a close relationship I think in many ways that this clinic has with their patients and I think we've learned some lessons from going through this. There are a lot of practical barriers to individuals within minority populations to participating in a study. These involve time, money, transportation, health, language. They have trouble getting out of their, getting time off from their jobs. They have less money in the first place so they have, so things like the gas to get there, loom much larger, they're usually sicker and we know that from health disparity research so everything else takes a back seat. And historically there's some less tangible but nevertheless just as important issues and such as trust and active aggressive targeted measures have to be taken to ensure good participation. So trust can be surmounted in some ways I think by working with a really dedicated community clinic that provides care to the people. So if you can combine the research and the clinical care you will really augment I think the participation in studies. In doing this however you run into real challenges working with non-academic clinics. Everything from IRBs to workflows become loom much larger and much more difficult. The health of minority participants are sicker than their non-minority counterparts and thus coordinating clinic visits with the research visits is really essential. And you need to go to where the patients are. We take, it's a four hour round trip, road trip when we go out and recruit and give patient results back. Language obviously for the Hispanic population especially is going to be very important. Using facile and easy interpreter access in person and on the phone is really important along with participation materials that are translated. And then you have to pay for the incidentals that you might not think of in many contexts. You have to be able to write notes for people to get out of work, provide monetary incentives for surveys. And the minority populations have a higher rate of changing contact information so you need to have backup information for that. And the thing I would end with is this means that it's more expensive per patient to enroll minorities and we have to take that into account as we go forward with Cesar. So thanks. I think we have a few minutes for questions as we transfer over to Carlos who is going to be presenting by phone. So Jim thanks for a great presentation and one of the things that strikes me is that the lessons that you've learned through your project is really lessons that have been learned in several other settings. And I just wonder what thoughts you might have about how to build upon that collective knowledge and experience to have a different outcome as things move forward. Yeah. I think it's instructive what you say is really true, right? How many times do we have to learn this lesson? Because one of the overarching goals for NC Genes was to ensure robust minority participation. We have expertise at UNC in doing that and yet we still had to relearn some of these lessons and I think that reflects perhaps both, you know, some deficits in our planning but I think it also reflects the difficulty of getting some of these fairly basic lessons out there. And I think that for CSER 2.0 we just really have to be aware that it's not going to be good enough just to say that, okay, we're going to create these grants, these efforts within areas that have minority populations. We're going to have to use targeted, conscious, methodical approaches to ensuring enrollment and then continued sustaining those populations in the study. Jim, as you know, we're going to have a session at the CSER meeting tomorrow on this topic and so I had to review our data because I'm at the site that has enrolled the most Hispanics. And I just want to emphasize your issue about loss of work. I think that we have to be incredibly sensitive to issues around, you know, all of us have jobs that if I go for an extra appointment I don't lose my job and I actually don't lose any income. That is not true of much of America and I think that we really have to be extraordinarily sensitive to that. This came up on the Pediatric Think Tank with a recommendation about how to disclose results and recommendations that you disclose in two visits. I know that the parents we deal with could never make two visits. So I do think there are ways in which we have to think about it in all steps of our protocol but I do think we've underestimated the importance of not having people miss additional work to carry out our studies. Yeah, I couldn't agree more. I was blown away when I was at an intern years ago realizing people had to take vacation time, precious vacation time just to come to a rock. I wonder if you want to comment on the role or importance of having people from ethnic groups that you're interested in recruiting as part of the research team. Yeah, I don't have actual data on that, right? We haven't done a trial that shows that. It's hard to imagine it isn't important. Now that said, so especially for example, that's why I put down Native Speaker, right? I suspect that having a Native Speaker helped our Hispanic recruitment. Having said that, it's really interesting the clinic we've worked with, the cardiology clinic in eastern North Carolina, Hassan al-Hassani, is Syria, right? And his team is almost all Caucasian and yet they have an unbelievable rapport with their patients. So I don't think it's, and there may be actual data on this, but at least from our observations that isn't, perhaps necessary, it might be desirable, but the key is having a trusting relationship and that's what makes it so effective to go into a clinic that really cares for these people day in and day out so they don't see the researchers as some foreign body that's intrusive into their lives. So I see one, two, three. I'm wondering if we should maybe try and get Carlos' talk. Perhaps some of his slides might address these same points. Carlos, I think we're ready for you. We have somebody ready here to advance their slides.