 Dr. Tracy Kugler who's an associate professor of pediatrics. Tracy's board certified in pediatrics and pediatric critical care medicine, completed a fellowship here at the McLean Center as well. Tracy's the medical director of pediatric intensive care unit, director of the pediatric burn care at the University of Chicago. She's an assistant director of the McLean Center and she co-directs the Ethics Consultation Service and Tracy is also the vice chair of the University of Chicago Medicine and Institutional Review Board. She is a nationally recognized expert in the area of thermal injury, pediatric organ donation, particularly after cardiac death and Tracy is going to talk this afternoon on research on organ donors. Tracy. Thank you. I'm no longer the medical director of the PICU. We had to get rid of something. That's okay, not a problem. The person that's doing it is well qualified and I wish her the best on a daily basis. Okay, so I'm the non-surgeon in the group but I have been on a national organization, a national committee for HRSA to help try to figure out how to answer the question of how do we do research on dead organ donors and these will be brain dead donors not donation after cardiac death donors. So we'll make our lives a little bit easier today. I'm also a paid consultant for Gift of Hope's critical care committee but I actually started getting paid for them after I really finished most of my work for HRSA and they really don't intersect at any point at this point if they may in the future if HRSA gets federal funding to do what our committee finally suggested. So what's the issue? And we've heard several transplant talks today. The issue is that there's not enough organs for all the patients on the organ donor list. Most the biggest being the kidney list. The kidney list is over a hundred thousand. We talked about how living kidney donors are at risk earlier this morning and so fundamentally we're still trying to find ways to get more organs out of the same number of donors for the dead donors. If we look at brain dead donors there's about 8,000 a year. That number really has not changed despite lots of different things. So now they're going to the next thing. How do we increase the number of organs per donor? Each donor could donate up to seven organs but fundamentally I will tell you that's the healthy teenager. Most donors donate three. So the transplant surgeons primarily are now looking at ways to try to get from three to seven on more donors without having to essentially have the totally healthy donor who has some sort of wayward tragedy, gunshot wounds, car accidents, etc. that lead to them being an organ donor. And there's currently many innovations because surgeons love to use them to innovate instead of research. Many innovations and some research protocols that are being done by individual organ procurement agencies as well as individual transplant surgeons all over the country and this has been happening since the beginning of transplant time. It is how we got where we are today so it's all good and retrospect. But moving forward the studies are going to get more complicated and more risky to the other organs and how are we going to deal with that? So this is some of the research that's been done. Region five which is these are all OPO regions. There's 11 regions I think. Don't quote me on that because I'm thinking about it now. They just wanted to see if meeting donor management goals increased expanded criteria donor kidney, expanded donor criteria organs. So fundamentally if you actually did at the bedside when you were preparing a brain dead donor to donate, if you did everything you were supposed to do, did it actually lead to more organs or was it really just a waste of time? Because it now takes them 24 to 48 hours to repair a brain dead donor to donate. They've also looked at dopamine for kidney transplant. They looked at imocidal cysteine for liver transplant and imocidal cysteine is what we typically use for Tylenol and overdoses. Methopritinus alone which is a steroid for liver transplant. They're taking lungs actually out of the donors and putting them in a perfusion box and calling it lung in a box. This is actually a formal research project across the country. And the surgeons at the meeting kept talking about do we start doing immunosuppressives in the donor? And would that work? Immunosuppressives in the donor are an interesting idea, but I will tell you that most immunosuppressives hurt the kidney. And I'm not sure that and I wasn't really talking to a lot of kidney transplant doctors. And so I think they get a little nervous all of a sudden giving immunosuppressives to the donor when immunosuppressives are going to be removed from the body by the kidney and maybe that's actually going to harm the kidney in the long run. So how do we start setting this up? So I think the primary question is whose organ is it? And I will tell you when you sit in a room with a group of OPO people and transplant surgeons and HRSA people and lawyers, it really gets interesting as to whose organ is it anyway. I think most of us think it belongs to the donor. And the donor's dead. So then the body goes back to the family. So it's the family of the donor. So that seems pretty simple. But then at some point it's out of the donor. And on the recipients back table of their OR. So is it then the recipients? The organ procurement agencies and the United Network for organ sharing clearly believe that at some level they have some control over these organs as well because it's under the federal guidelines that all of this occurs. And so they would like to have some control over it. And it's the OPO employees that are doing the things to the donor to prepare them for the OR for donation. And so it's their employees that are going to be doing whatever has to happen if there's research done during the pre donation period. The donor hospital may actually think they have some claim to it because the patient that is donating is sitting in their hospital. And so do they have some claim. And then the transplant surgeon wants the best organ for his or her patient. And so therefore he or she is going to say that they have some claim to it. And at some point that organ is in the recipient hospital. And so does the recipient hospital have some claim to it. So let's start with the uniform anatomical gift act, which is our federal guideline that sets this up. The act allows for individuals to gift all organs and tissues for transplant, research, education and therapy. And it sets it up through donor registries in all the states. It's primarily with driver's licenses, although in all states now you can actually go to the website and sign up even if you don't have a driver's license. And in doing the study I've now signed up in several states that I don't have a driver's license. They respect first person consent, which means that if you have signed up to be a donor, it is supposed to be respected if you're 18 years or older and you signed it at 18 years or older. And you're not really supposed to be requesting from the family, but you're supposed to be notifying the family. And OPO's now have access to the state registries, which in the past they did not. But there's lots of state variation about how we actually sign our organ donor cards. And fundamentally we never really give informed consent for these donor cards, because no one at DMB or even at the website really explains what happens if you're an organ donor. So in Illinois you register as an organ tissue donor. In Virginia, and I didn't do all 50, but here's four examples. In Virginia it actually says all organs, eyes and tissues for transplantation, research, education and therapy. But if you don't like that wording you can specify your gifts on the next page. In Texas you say all organs and tissues for transplant and for research, education or therapy purposes if they are determined unsuitable for transplant or you can click all organs for transplant only or you can specify your gift on the next page. And then in Oregon under other limitations where you can click is a positive click. My gift of organs, eyes and tissues may not be used for medical research. And there is an explanation there that states that research and education only occur if they're not transplantable. So you have to click that you're not interested. And I'm sure if I went to the other 56, 46 states I'd have even more different views, but that gives you a broad range. So that helps but it doesn't completely help and I will tell you that the OPOs don't want to go back to all 50 states and get it uniform in all 50 states because that's problematic in and of itself. So then who's going to review these protocols? If the uniform anatomical death access, yeah you can do it but it's not perfect. So do we look at the use in individual institutional review boards? Number one that's a lot. Gift of hope has over a hundred donor hospitals. So from a donor side that's over a hundred hospitals. But the bigger issue is institutional review boards don't review research on dead bodies. They only do it on human subjects that are living individuals. So most IRBs are going to say we don't want to touch this. Or if they do want to touch it, it's fundamentally does not fall under the federal guidelines for the IRB and they're doing it as something extra. So you can get an ethics committee to look at it and some people's ethics committees are very willing to look at it. The University of Pittsburgh wasn't real excited about having their ethics committee look at it either. So they actually came up with a new committee that was a policy on research of the newly dead. And that's the committee that looks at it at their institution. But probably the hundred hospitals that include a lot of small hospitals at gift of hope are not going to set up those committees. And their ethics committees are going to be a little nervous and their IRBs are going to be a little nervous because they don't review a lot of research. The big hospitals can probably figure something out. And we're going to have OPO's that need to review it. We're going to have donor hospitals and we've also got the recipients hospitals. Although most of those again are big teaching hospitals that are transplant center so that will be a little bit easier. So let's back it down a little bit more and let's go back to the ethical principles. So let's go back to the Belmont report which is where research looks at. And it's respect for persons, beneficence and justice. So who are we respecting when we're respecting the people. We have to respect the donor even though the donor is now dead as well as respect the recipient and also perhaps the donor's family because they're in the mix here. Beneficence do no harm. Well if we're doing something on a donor body are we harming one organ in order to make another organ more usable. And justice, are we making recipients research subjects whether they want to be or not because is the only way they're going to get these organs is if they're research subjects and is that fair. Or do we not do the research unless all seven potential recipients say oh yeah that's okay. And how do we figure that out because many times this research would start fundamentally before those seven people are identified. We need to respect the gift because many people that sign their organ donor cards really do want to be organ donors. So we want to respect that gift. We also want to respect what their thoughts are on research. But for the most part that's not really asked. Or it's asked in a very short format on your driver's license that you may or may not understand. But we also do need to respect the survivors. We need to respect the families. They're the ones at the bedside as those of us that work in the ICU know that we actually need to respect because they're going through a lot of person's death. So I think I've talked about a lot of this. Donors autonomy to make the gift and it's donors altruism is fundamentally what it is. It also frees the family from hard decisions. There's one less decision the family actually has to make. And there are many studies that show that people are more likely to consent to things for their own body than they are to consent for people. That they love. Which is one reason why the new data comes out that families that have to decide to withdraw life support on their family members in the ICU. Have post traumatic stress. And making decisions about organ donation may end up doing some of that too or it may be why some families just say no because they just don't want to deal with it. So what does that respect me. I think we have to make sure the science is sound. And we have to notify the family when interventions are going to change the normal donation process. If additional tissue is going to be taken it's going to take additional time. Or if there's going to be additional studies especially if they're high risk because right now we're already doing bronchoscopies and liver biopsies and sometimes even cardiac caths on donors before they become donors in the OR in order to make sure those hearts and lungs and livers are appropriate for donation. So who can say no. Can the donor family overrule the first person consent that's very general for research. And or even for donation even at times the debate comes up about donation. Most OPOs are really trying to hold the line that they're holding it up for donation but what about for research. Is there a time that the donor family cannot overrule. So the discussion at the meeting was well the family says no to research the family says no to research. And the transplant surgeon said well if the liver is on my back table and the recipient has agreed to be in a research project in which I'm going to do something to deliver on the back table before it is inserted into him. I'm going to do that research. Because it's now my recipients liver it's not the donors liver and it's not the donor family that makes the decision. I don't know. To me that makes some sense but when does it become the recipients liver and not the donors liver. And who makes that decision. And so the organs after recovery I think are much different research projects than the organs pre-recovery. Can a recipient overrule and how are they going to overrule. When are we going to tell them. Can a medical examiner overrule. Because in some jurisdictions they like to overrule lots of things. And can the recipient surgeon overrule. So you have seven surgeons you have seven opinions. Who are you going to listen to. The kidney doctor because there's fewer kidney there's more people on the kidney waiting list. Or the heart surgeon because he says he's got a patient on an LVAD he's going to die in 48 hours if we don't get the heart. How do we make these decisions. So consent issues for the donor. Some people want the long detailed research consent. I think this is not going to be helpful for a recipient family. I mean for a donor family. They're already morning they're already exhausted. I will tell you they've already gone through a three page consent for donation. They want to donate that the person wants to donate if the research helps wouldn't they just say yes. And they already get asked do you want to use the organs for research is that I think that's sufficient for them. But I do think they may need to know about special things. And if the person consenting for research is efficient. This is not part of the registry. Studies going to potentially harm some organs to protect others. So it's going to potentially decrease the gift. It's going to potentially decrease the availability of the organs. How do we set up this priority system. This timing of the study matter I've already talked about this pre donation post donation operating room. What's going to be the outcome of the publicity of this research when it gets published what is the public going to think. Is it going to increase donation rates. Is it going to decrease donation rates. I think that's a big question. I don't know. So who don't can sense the donor family if we're going to do a formal consent. Is it going to be the same OPO representative. Is it going to be the physician in charge of the research by Skype. Is it going to be a recovery surgeon. 15 minutes before the recovery. How is this going to happen. I think fundamentally it's going to have to be the OPO. But the recipient consent issues also become an issue. So we're going to have to discuss the potential recipients ahead of time. So right now potential recipients are already are talked to by their surgeons about expanded criteria. Donation after circulatory desk. And high risk donor such as HIV or with high risk donor behaviors known HIV or have B positive. And recipients already have to make decisions about those prospectively. So now I think they're going to have to ask about research organs. But how much risk is a research organ going to have. I think some of them are going to have no risk. But they still will have had research done on the donor body. Some are going to be minimal risk and others may unfortunately moderate risk. The we talked about that the high risk would not be envisioned in the current system at least starting out. But the problem is that organs are allocated nationally. So California may be doing a research project and the kidneys may go to Virginia. And so how are we going to do that consent. When are we going to learn what the actual study was and notify the recipient that there's an offer. But he may have to participate in a research project. He may have to get extra studies done. We can't mandate participation in the research study. We have to follow recipients of organs. Mandatory goal of research is to determine outcomes of the donated organs. So we have to follow them. So how do we do that. Thankfully UNOS maintains a database. Is that going to be sufficient. We can't refuse organ recipients because they don't want to participate in research. We have to ensure the safety of the recipient. So we may have to have some sort of safety of follow-ups that's mandatory. And then we have to attempt to consent in a stress-free level which is not going to be at the time that the organ becomes available. And so how do we do that. So I'm going to end it there.