 On behalf of the McLean Center for Medical Ethics, I am pleased to welcome you to the first lecture in the winter quarter in the seminar series on ethical issues in end-of-life care. One very important message to the regulars here, there will not be a session next week. I repeat, there will not be a session a week from today on the 14th. We will resume our regular weekly sessions on January 21. I'll repeat that announcement for those who are out of the room at the time. It's my pleasure to introduce today's speaker, Dr. Tracy Kugler. Dr. Kugler is an associate professor of pediatrics and the vice chair of the Institutional Review Board. Dr. Kugler received her MD from the University of Virginia, completed her residency at the University of Cincinnati, and then completed fellowship training in pediatric critical care at Children's Hospital of Philadelphia, and then did a clinical medical ethics fellowship here at the McLean Center. From 2007 to 2013, Tracy directed the Pediatric Intensive Care Unit here at the University, and also directed the Pediatric Burn Unit. Currently, Tracy is co-director of the Ethics Consultation Service. Dr. Kugler is nationally recognized for her expertise in thermal injury and pediatric organ donation, and has done extensive research on challenges and end-of-life care. She co-authored a paper called A Call for Full Public Disclosure for Donation After Circulatory Determination of Death in Children that was published in Pediatric Critical Care Medicine. Dr. Kugler has also published on parents' reactions to participating in end-of-life decision-making on decisions regarding their children. Today, Tracy is gonna talk to us on the topic that you see up on the board, research on the dead organ donor, consent and regulation conundrums. Please join me in giving a warm welcome to Dr. Tracy Kugler. Thank you all for that warm welcome. As a disclosure statement, I have switched my topic. If you all saw the earlier ones, I was gonna do donation after cardiac death, which I've done about a dozen times in various forms throughout this institution. And I have changed the topic because I am currently involved on a national committee to figure this out that is set up by HRSA. And we are probably moving towards a national central IRB to do this. And I wanna get some thoughts about where we're going. I will tell you that most of our conversation has been about the recipient. So I'm going to try to talk about the donor today. But after I have a discussion period, after we talk about the donor, I'll talk about, if we still have time, I can talk about the recipient issues and discuss those as well. But since we're talking, this is a death and dying seminar, I'm gonna talk about the dying donor and the donor issues is where it's gonna come from. So first of all, just to go back through where organ donation has come and started. The first kidney transplant was in the 1950s. And then in 1967, we had the first heart transplant by Christian Bernard. In 1968 was when we first defined the Harvard criteria for brain death that has recently. And then in the 1970s, the United States developed the United Network for Organ Sharing. This is the national organization under HRSA that fundamentally, that keeps the database of everyone that is awaiting an organ and helps determine which organs go to which recipients we're across the country and sets all the rules and regulations as to how those organs are allotted to the different areas. In 1981, the guidelines for the determination of brain death were determined for this country for adults. The pediatric data did not come out until 1987. In the last three years, both the adult world and the pediatric world have changed these criteria. In the 1980s, immunosuppression really became available. And that was when these transplants really started to take off and work because the immunosuppressants of the 50s, 60s and 70s were fundamentally just steroids. And that fundamentally just did not provide enough for long-term survival. But with the advent of the new immunosuppressants of the 1980s, we had long-term survivors. And then in 1992, in the United States, we had required request legislation, which means that every patient that dies, their family is supposed to be asked about request. A lot of feedback. And then that has been moved to even first person consent and first person consent means that now in all 50 states, if you have signed your donor license, if you have signed your driver's license that you want to be a donor and you're 18 years of age or older, then that is going to be respected. And it's no longer asking your family if you can be a donor but notifying your family that you will be a donor. And that has now gone through in all 50 states. So I alluded to this, but just to make it totally clear, the Oregon Donation Policy in the United States is fundamentally run by the federal government. And it goes under HRSA. HRSA is under the Department of Health and Human Services and they set all the policies and they set how all of this works. They have a vested interest in this because if you're on dialysis, you qualify for Medicare and Medicare falls under HRSA as well. So they are trying to get people off the kidney transplant wait list and get them transplanted. And so that is why they have a vested interest in doing this. They have set up UNOS and UNOS is the organization that sets all the policies for where the organs go. And there's been a huge evolution of that over the years. It used to be that you, they fundamentally started in the local area and that is rapidly changing to essentially any organ can go anywhere in the country. And that's a big change for transplanters and for organ procurement organizations across the country. And then another organization, what am I running into? Another organization that's important is the Organ Donation and Transplantation Alliance. And this organization is set up essentially of all the organ procurement organizations and various transplanters that are interested in promoting organ donation. And by doing that, it is that organization with HRSA that is looking at what we should be doing about research on these organ donors. Some terminology that I'm gonna use just to make sure everybody is clear. Heart beating dead donors are brain dead donors. I'm gonna call them brain dead donors, but if you are reading the literature, it may say heart beating. Donation after circulatory death or DCD. I actually am not gonna talk about this very much in this talk, but it may come up. And so those are patients that die from cardiac deaths. And then expanded criteria donation is essentially loops together all patients that don't fit into the ideal criteria. So all the donation after cardiac death patients, but also the older patients or the patients that have got pre-existing illnesses that may make them not as great of a candidate as we might think otherwise. If you've got significant hypertension, all your organs may be somewhat affected. If you have HIV, if you have hepatitis B, all of those things can be affected, but at this point, all of those organs are potentially used in some recipients. So brain dead donors. We've done lots over 30 years to try to increase the number of brain dead donors because they are essentially the gold standard of what we want for donation. But despite that, we're essentially at 8,000 a year. Why are we at 8,000 a year? Number one, I think it's the number of patients that die from brain death criteria in the United States. And we don't really want that to increase. It's mostly trauma patients. So it's mostly gunshot wounds and car accidents and other significant injuries. It can also be stroke patients and aneurysm patients. But fundamentally, it's a very small group of diseases, so to say that patients lead to brain death. We've increased organ donation rates and we're trying to approach 75% across this country. We are definitely doing better than we have been, but fundamentally, I think we've sort of reached a nadir at that level as well. So the only other thing we have left is to improve the number of organs per donor. Seven organs per donor is possible. In my 15 to 18 year old patients in the PICU, we get seven donors a lot, seven organs a lot. But in the 40 to 70 age group, you don't rarely get seven organs. And the reason you don't get seven organs is that we've been drinking, we've been eating bad food, we're overweight, we've done all the things that make our organs not so great by that point in time. But my teenagers haven't done enough of to get there yet. So for most of them, the most number of organs is two or three. So what have we done to try to improve this? We've done lots of things and most of what's been done has been done in the name of innovation or has been done in the name of research. But it's a little unclear to me as I even read some of these early papers as to exactly what some families were told there was research. Some families weren't told there was research. And sometimes we just publish this as our experience and this is the innovation. So the first thing that came up when the 1980s, the University of Wisconsin started, had developed their own preservative which became known as the University of Wisconsin solution or bias fan. And there have been subsequent changes to this but this fundamentally is one of the gold standards that many transplant institutions still use to preserve the organs. In the 1990s, there's lots of case discussion about endocrine therapies and they started using endocrine therapies, thyroid replacement. Insulin therapies, steroid replacement. And lots of people were doing it in lots of different ways. I was in training at that time and as I changed institutions, our policies with our OPOs changed and even coming here they changed. Every OPO has their own way of doing this. It's slightly different. There's some data out there but again it's many times case reports. There's not a lot of randomization. And then in the 2000s, all of a sudden all of my organ donation patients are getting lots of antibiotics that my infectious disease colleagues think are crazy. To protect the gut, to protect the lungs, to protect all sorts of things. And I don't know that there's a lot of data out there. It's 24, 48 hours of broad spectrum antibiotics that we haven't given in the past but they think are going to make the transplant a better thing. And what happens to a brain dead donor? On a routine basis, none of this is research. In 2018, and this is mostly for the adult donors. We actually don't have to do all this in a pediatric donor because again, their organs work. So they all get critical care for 24 to 48 hours while the organs are placed, while all of these tests are done, while the transplant teams are brought in. They all undergo an echo or multiple echoes. Adults undergo cardiac cath. If they're a potential lung transplant candidate, they undergo a bronchoscopy. If they're a liver transplant candidate and they're an adult, they undergo a liver biopsy. And for many of the larger organ procurement organizations like Gift of Hope, Gift of Life in Philadelphia, they actually have now set up some freestanding surgery centers for lack of a better term that have ICU's and OR's and they will transfer the adult sub-patients to those units and actually manage them there because they can go to the OR when they want to go to the OR and they don't have to wait till midnight because here all donors go to the OR between midnight and six a.m. It's when they go because all of the other cases have to be done for the day and you have to get it done before the 730 started the regular schedule. So all the donors go between midnight and six a.m. And this way you can actually go when you want to go. So I just have some cartoon slides just to... I'd like to be an organ donor. You don't have the guts. No, you're thinking of the lion and am I. So how do we do organ donation? What is the basis of organ donation? It's the Uniform Anatomical Gift Act, which was last amended in 2006. And this amendment essentially allowed the first person consent. This is a federal guideline that then has to be enacted in every state. Not all parts of it have been enacted in every state as the last view that I was able to look at online from 2015. There's like three states that haven't enacted it in its entirety. It allows for individuals to gift all organs and tissue for transplant research or education and therapy. I'm not quite sure what therapy is, but for therapy. But it's the research, and fundamentally most states we really concentrate on the transplantation and the other two sort of get forgotten. But fundamentally this act allows you to donate your body for research and allows you to donate your body for education. So this is how we all get cadavers for our anatomy labs and for the surgeons and for other people that wanna continue to use cadavers for their ongoing education and potential research. It also allows for donor registries in all states and these donor registries are now first person consent. And so as I said, if you sign your driver's license you now are an organ donor. If you qualify medically to be an organ donor it's not a question for your families. And now the organ procurement organizations actually have access to the state registries. Now it is my understanding that Gift of Hope does not have access to California state registry, but they have access to Illinois and Indiana's because they also cover Northern Indiana. So what do these registries do? It's amazing, they're very different. In 14 states the registries actually ask you about research. 14, not the state of Illinois. So in Illinois, when you go to the registry website it says do you wanna register as an organ tissue donor? And that's really all it says. And you mark yes or you don't fill it out and then you're a no. There's no discussion at all of researcher education. It does discuss that it's first person consent and it does discuss that if you're 13 to 18 so I guess actually 13 year olds in the state of Illinois can actually register on this registry even though they wouldn't have driver's license. That your parents will make the final decision about donation. So I called Gift of Hope and I said, so how do you do this? So Gift of Hope has changed their authorization form which I'm actually quite thankful for and they sent me a new copy yesterday. So this is what is filled out by the family when they go to tell the family that your loved one has asked to be an organ donor. It says at that point they ask I authorized tissues and blood samples in any organs not eligible or able to be used for transplant to be used for medical education, research and development or stored for such use in the future and they can answer it yes or no. So fundamentally it becomes the wishes of your family for you. It states that all your medical records are gonna be reviewed. It states that there's gonna be infectious disease testing which is gonna be your HIV and hepatitis, et cetera. It states that there's recovery of additional specimens to verify medical suitability and it talks about transportation to a possible surgical center and it states that there's gonna be certain diagnostic tests and the certain diagnostic tests equals the bronchoscopy, the liver biopsy, the cardiac cath, the echo. They don't get individual consents for those things. So I've just mattered some others. So Virginia, when you go to their website it says I donate all organs, eyes and tissues for transplantation, research, education and therapy. That's what Virginia says. That's what you say okay to when you sign your consent. Or it says I would like to specify my gift on the next page. I couldn't get to the next page because I couldn't register in the state of Virginia but essentially that would be the process you have to undergo. Texas also says all organs and tissues for transplant and for research, education or therapy purposes if they are determined unsuitable for transplant. Or you can choose all organs for transplant only or you can specify your gift of donation on the next page. And then they have another question. Have you signed up for a body donation program? And if so, which one? And then they list like 20. So this would be do you wanna be a cadaver? So I found that interesting. Now remember, you're probably doing this at the DMV. And the last time I went to the DMV and I signed my organ donor card, the lady looked at me and she said, oh, you don't wanna do that. You have no idea what they do if you're an organ donor. And I worked about five seconds, thought about a long discussion and then said, no. I said, I do, I appreciate your comment, I do. But I don't think the people at the DMV are gonna be particularly helpful in helping you fill this out or explaining what this is. And there are little pamphlets that maybe will be at the DMV and there is additional education on these websites. But I don't know how many people go to the education on the websites versus filling out their donor card when I go to the DMV. Organ is the third one I'm gonna show you. It has donor limitations. You can put a checkbox. And if you check it, it says you can check which of these organs you do not want donated. You're gonna list heart, lungs, liver, kidney, pancreas, small intestine eyes, cornea, heart valves, and associated tissue, skin and bone and connective tissue. I'm not even sure everyone's gonna understand what all those words are. Or there's another limitation that you can check box that says my gift of organs, eyes, and tissues may not be, I'm sorry, it says many, may not be used for medical research. And there is an explanation that states that the medical research is only going to occur if the organs aren't transplantable. But we're talking that these organs that may be other research. So Calvin thinks he can do a mucus transplant. His mother tells him that's not such a great idea. So, organ donor research. Signing your organ donor card, does it really cover it? Is saying you can use my body for research, is that good enough? And is that what anybody really, are we reading the fine print when we're signing our organ donor card? And do we understand it? So organ donor research that's been done recently and has been published. Region five of the UNO setup, because UNO says 11 regions, and this is essentially the Southwest, California, Nevada, New Mexico, Arizona, and Utah. Got $2 million from the federal government to see how we can maximize organ donors in the ICU. What a great study. It took them forever to get anything done because what happened was is every potential hospital is an organ donor center. So do you have to go through every single IRB? Do you have to tell every single hospital? Because their nurses are taking care of the patients, so their nurses, therefore, are participating in research. Or do you have to send them all to a surgery center? And just do the research at the surgery center. And then all of a sudden transplant surgeons went, we give that to organ donors? I don't want that for my patient. How can we be doing that? It was just total chaos. And I will tell you, it was probably this $2 million that led to the committee that I won. Because the head of the committee is the trans planner that fundamentally had that $2 million. And he's like, this is driving me crazy. He's gotten some publications out of it, but let me tell you, it's been hard. And fundamentally, it was doing what we need to do to try to increase the number of organ donors. They've used dopamine and have looked to see how that affects kidney transplants. Now, if you're an ICU doctor, you know that dopamine used to be the best thing since sliced bread, and now it's, we don't want to use it at all. And so now they're gonna be restarting it in some donors that we wouldn't have used when they were progressing to brain death. But all they looked at was the kidneys. They didn't look at the lungs or the heart. And we think dopamine is now bad for the heart. I don't really know, but, because the data goes up and down, depending on what cycle of the data you're in. But all they looked at was the kidneys. And was that really okay? Because we used other organs out of those donors. Somebody else used anesthetial cysteine for liver transplant. So they put anesthetial cysteine into the donor. What's an anesthetial cysteine? It's what we use for Tylenol ingestions. And it's also what we use to protect kidneys when kidneys that are already damaged when you're undergoing a CT scan to protect you from the dye of the CT scan. So they find that it improved liver transplants, but we don't know what it did to the other transplants. And some surgeons, when they found out that the patient had gotten anesthetial cysteine because the liver transplant people had said, oh, give them anesthetial cysteine because that's the research we're doing. They went, oh, why weren't we told about this? Methoprednis alone for liver transplant again. Many places use steroids. This was actually a study using bolus steroids versus a continuous infusion of steroids. But when it came up, there were pancreas people who said, what do you mean donor gets steroids? Plus if the donor gets steroids, does that affect how much steroid the recipient should get the first night? Because almost all recipients get steroids in the OR too. And so should we be somehow or another calculating the difference if you get more steroids in the donor? And then another one is lung in a box. So we've been perfusing kidneys for years, but now they're perfusing hearts and they're doing research study to perfuse lungs. So they're taking the lungs out and they're putting them in a perfusion box and they're keeping them in the perfusion box to see if they can be used. But that means they're taking lungs out of a patient that they may or may not use for donation. So what do they wanna do in the future? Potentially give immunosuppressives to the donor. But again, is that gonna hurt some organs while helping others? Could it be organ specific? What, how are we gonna do this? In looking things up, Hopkins with the assistance of Dr. Gottlieb, who I don't see here in the room, but his name's on the paper. They looked at taking the chest wall thymus and a heart vascularized composite allograft, which fundamentally is like the front of the chest for use in pediatric heart recipients so that they could take potentially bigger hearts for pediatric patients and to help improve the compliance of the chest wall. They've only done this, all they wanted to do was prove that they could take all of this out in a cadaver. But it was a two-hour surgery. And when the surgeons come for a donation, you've got all potentially seven surgeons on a pediatric patient waiting around for their organs. And let me tell you, the heart's gotta come out first and if they're gonna wait two hours for the heart surgeons to do their part of it, they're not gonna be happy. But that's potentially what's gonna happen. Plus you're gonna end up taking the chest wall. So the kid's chest isn't gonna look exactly normal. We always say you can have an open casket. You can still have an open casket because the kid's gonna have some sort of a shirt or dress or something on, right? But the chest is not gonna look like it normally would because you're taking the anterior ribs. And then we still need some critical evaluation of some of our current practices because we're doing a lot of things that we don't really know if they help or don't help, but we're doing a lot of things. So how long have we been doing research on the newly dead or neomorphs? And all of these studies that I'm gonna talk about are on brain dead patients. So the earliest one I could find was in Journal and Pediatrics in 1980. It's amazing to me that we started out in kids. Like really, inappropriate secretion of anti-diuretic hormone and the effect of lithium in its treatment. And this was in Spain. And essentially they took a brain dead child and they watched her anti-diuretic hormone levels go crazy and then they gave her lithium to see what that would do. She spent an additional 24 hours in the ICU. Now in 1980, there was no criteria for brain death in pediatric patients that was published. There was no criteria in adults. The criteria in adults was in 1981. The Harvard criteria was 1968, but that's when the million was a permanent comatose state. And the pediatric data came out in 1987. And Norm Faust, who is a well-known pediatric ethicist, wrote an editorial to this stating, what are we doing here? We don't even know what brain dead is in a pediatric patient in 1980. In 1981, at the University of Florida, they did an esophageal operator airway study in brain dead children. So this was some new fangled airway that was going to be used when you couldn't intubate a patient. So they wanted to see if it worked. So brain dead kids were intubated. So they said, well, we can take the breathing tube out, we can put this in, we can hook it up to the ventilator, and we can see if it works. And then the discussion was, well, after they had figured out if it worked or not, do you take it out and put in a breathing tube again, or do you just let them stop everything because they're dead? But again, in 1981 in the United States, we didn't even have good criteria. They did just let the patients die. And then inhibition of human platelet function in vivo with a monoclonal antibody. This was at the University of New York. This was in adults. They took, again, just one adult. It's always just one to two to three patients and gave monoclonal antibody to see what it would do on the dead body that was still in the ICU. And then MD Anderson and, MD Anderson and the University of Pittsburgh both had big articles in 2002 that actually led to New York Times and Chicago Tribune articles and lots of other articles and led to lots of discussion. So MD Anderson took cancer patients who were dying in the ICU or were brain dead. And they stated that they decided to do this because there were lots of families in the ICU that were saying we wish our patients could, our family members could be organ donors and if you have active cancer, you can't be an organ donor for the most part. So they asked the families, well, can we use them for research? And they infused a large number of peptides into their bodies and let them circulate for a period of time and then allow them to die and then looked at their bodies to see where those peptides went. And those peptides are probably what's being used today for specialized cancer therapies, but they were using brain dead donors. This was reviewed by the IRB at MD Anderson. They thought it was a good thing for them to do and we'll get to why that may or may not have been. The University of Pittsburgh did the same thing. They had a new device and it's interesting they're trying to keep it but potentially like an artificial heart or something that they had tested in large animals but they wanted to test it in ideally dead humans before they tested it in live humans. So they said, well, we can do it on brain dead patients. They sent it to their IRB and their IRB said, we don't do dead people. That doesn't fall under IRB protocols and it doesn't and I'll go through that later. So they didn't feel qualified to do it. So then they talked to their ethics committee and their ethics committee, Honda and Haw and said, well, maybe, maybe not, we're not sure. So they developed a third committee called the Committee on Research Involving the Dead and this committee reviewed these type protocols. The University of Pittsburgh does a lot of dead research on dying patients and on the nearly dead. So they actually had nine protocols in one year which I think is a lot but I think it may just be because of the research that that institution is known for doing. So how do we set up this review? Who sets it up? What should we be doing? Because a lot of stuff is going on and it's sort of a mishmash as to what we're actually doing and what we're actually saying. So the Institutional Review Board, the federal guidelines state that we're only supposed to be looking at research on the human subject which is the living individual, which is not the donor. It will be the recipient if we're also looking at the recipient but it's not on a dead donor necessarily. So how do we look at that? The Ethics Committee, I think that's a great possibility especially if you've got a research ethics committee. It's a great possibility. And some institutions actually have policies on the research on the newly dead. The University of Chicago doesn't but some institutions do and then you can also follow that protocol. But then who should review it? Does the OPO review it? Or does every donor hospital review it? Which is fundamentally almost every hospital in the country. There's 150 hospitals that have the most number of donors but is it every single hospital that has to review it? And do the recipient hospital, should they review it from a different standpoint? And does the average IRB have any idea how any of this works? So the ethical principles as I thought about it. I said well let me go back to the Belmont Report because that's what we use as our basis for research on people. This is respect for persons. So we could change that a little bit to respect for the dead person. Or respect for the dead or making sure that we don't disrespect the body and the gift. Beneficence, again make sure there's no harm, make sure we are benefiting. Which means we need to make sure that the research makes sense and then we're not doing something that seems just crazy just because we can because. And justice which means that we are making sure that we're not picking out certain populations to do this on because it's easier than other populations. So that everybody has an equal chance to participate and an equal chance to be protected. So I revised it a little bit so I think we need to respect the gift. The body whether it's given as a cadaver whether it's given for transplant is a gift. And we need to prize that gift because they're precious and actually very few people give that gift. And we need to respect the survivors, i.e. the family, whatever that family looks like. Because they sometimes are at the bedside for that 24 to 48 hours. And they're putting off their funerals and they're putting off lots of other things. They're putting off part of that warning process in order to do this. I also think we have to respect the first person gift when we feel like it's been adequately done. And I'm not sure how we can guarantee that. Illinois guidelines, there's no discussion of research. So we clearly can't say that signing our driver's license has anything to do with research. But 14 states do. But I think the donors had the autonomy to make the gift and we have to respect that. And we have to respect that that fundamentally is an altruistic gift and we need to respect their altruism. It also frees up the family from these hard decisions because families really don't like to make these hard decisions. And in the ICU they've already potentially made lots of hard decisions or they've heard lots of hard things. And this frees up the family from that. And there has actually been a study where they interviewed family, interviewed people and said, would you donate your body for research? And many of them said yes. Would you donate your loved one's body for research? And they all said no. It's easier to say yes or no for yourself than it is for somebody else. So what do I think the respect means? We have to ensure that the science makes sense. But again, we don't have a researcher that's like, oh, well I could do this, but that the science really doesn't make sense. I think we do need to notify the family when the interventions are going to change things that are important to the family. Whether it's changing the normal process, whether it's gonna take longer, additional tissues taken, additional time is used, additional studies, especially if they're high risk. But who's really authorized to say no? Can the donor family overrule the first consent? I don't think so. But I think that they need to be notified. Is there a time, and is there a time that the donor family really shouldn't be able to overrule? What if the recipient agrees to a study that fundamentally is gonna be done on the organ on the back table before it goes into the recipient? Whose heart is it? Whose lung is it? Is it still the donors? Or is it the recipients? Because it's now on the back table, the recipients are. I will tell you, we had this discussion in a meeting because the OPO person said it's still the donors and the recipient surgeons said, oh no, it's my, because it's on my table now. Who does it belong to at that point? Can a medical examiner overrule? Because 95% of my organ donors in my unit go to the medical examiner afterwards. And that's a whole other issue. And can a recipient surgeon overrule? Because the recipient surgeon may be in California and the research is being done in New York. How do we figure this out? Consent issues for the donor. The average consent is what, 18, 20 pages. Our consents are crazy for IRB consents, right? Do we really wanna take a mourning family and give them another 20 page consent? And does that really make sense? I personally am not convinced it does. The family's mourning, the family is exhausted. The family is not thinking straight. The family doesn't want to be inundated with lots and lots of details necessarily. They wanna donate or their loved one wants to donate. And I think fundamentally whatever has to be involved in that they go along with because they go along with cardiac casts and liver biopsies and bronchoscopies. And the kids in my unit get bronchoscopies and echoes and the parents are there. They go along with all this stuff. It's a lot of big stuff. And do we think the first person consents sufficient? And if so, do we need to come up with a way for all 50 states to do it on your driver's license? And is that really okay? So I think the research is potentially gonna impact the family. Anytime that you extend the donor in the ICU or the OR so that two or three hours if we do the cardiac block. And I went back and looked, our first run of this at the national level is to look at brain dead donors. We're not looking at DCD, but I know that in two years we're gonna be looking at DCD. So I went back and looked at the study in Colorado where infants use DCD hearts, which meant that the donors died in the operating room without their parents. It was probably a minute or a minute and a half and then their organs were taken and the hearts were placed in a child in the next OR. At that point in time, the only organs that were taken from neonates were these hearts. So fundamentally, this was a research project in which your child was not going to die in your arms because you had decided that your child would be an organ donor. But it was unclear when I read the New England Journal article that the donor families were told that this was a research project. The parents of the recipients were told and were signed to consent, but it is unclear to me that the donor family said anything more than I want my child to donate. And they said, this is how it's done. But that was fundamentally a research project. And fundamentally those family members were not there for the death of their children. And as a PICU doctor, I have concerns about that. Now, I have had families that don't wanna be there. And I have had colleagues that have rocked babies until they died because their parents don't wanna be there. But this is really a different situation. And it's unclear to me what Colorado did. Potentially some of these research projects may damage some organs while protecting others. And so that's going to reduce the gift. And so how do we set up this priority system and how do we set this up and how do we ensure that that doesn't happen? And I don't think we can be 100% certain that it doesn't happen. I can't be 100% certain that it hasn't already happened because we don't know what anesthetical system and dopamine and steroids did to these other organs because we didn't look. We just looked at the organ we were interested in. And again, does the timing of the study matter? So if it's an ICU intervention, the family might very well be there. If it's in the operating room, it may affect some families wanna see the body after the OR. If it's during the transportation to the recipient hospital, who owns it? Whose organ is it at that point? And if it's on the back table of the recipient OR, whose organ is it? Who owns it? And what's gonna be the outcome of the publicity of this research? Eventually it's gonna get out there, right? Someone's gonna hear about it and call somebody. It's gonna happen, just like it did in 2002 when it got to the New York Times and it got to the trip. It's gonna happen again. Is it gonna decrease organ donation rates? I don't know. Is there gonna be confusion? Is there a way we can create clarity? So for the donor family, if we decide they need to consent to something, how are we gonna do that? Is the OPO representative gonna do it? Is the physician in charge of the research gonna do that? And if it's the physician in charge of the research, if they're not at their institution, how do we do that? Or is it the recovery surgeon? If the research is being done by the recovery surgeon. So where are we doing it in person? Which means that we're gonna do it at midnight right before they go to the OR if it's the recipient surgeon, recovery surgeon. Are we gonna do it over the phone? Are we gonna create some version of Skype? How are we gonna do this? When? Are we doing this at the time of authorization? And I will tell you some of this research we may not even know about at the time of authorization. When the issue comes up, whenever that is. Or when the recovery team arrives. So there was a consensus panel that was developed by the University of Pittsburgh in MD Anderson after we looked at, after they had those issues and had the publicity about their two studies. And this is what they came up with what the research for the newly dead should look like. And it's very similar to what I've already talked about. Scientific and ethical review and oversight. It's that involve the community of potential research subjects. So what's the best way to do that? When fundamentally it's all potential organ donors, everyone who signed a donor card. Do we do some sort of education at DMV? Who does it? Who pays for it? How do we set that up? It needs to be coordinated with organ procurement agencies. It needs to not conflict with organ donation or required autopsy, or which is medical examiners. We need to use procedures that are respectful of the dead. Any research needs to be limited to no more than one day. First person consent is preferred. But general advanced research directives in surrogate consent are acceptable. We need to try to protect confidentiality. We need to make sure we don't impose any costs on the estate or on the family. But also no payments or inducements. And we need to make sure that we clearly explain to the family the ultimate disposition of the body and approximately when we think that's gonna happen. So what we think, so what HRSA has suggested we set up is a central IRB for donor management research. But this is gonna be a little bit more than a central IRB because it's going to discuss the donor and the donor doesn't fall under the federal guidelines for a central IRB, for an IRB. And it's also going to really strongly look at the scientific merit. And IRBs look at the scientific merit, but you may have, but many times our IRB, if we're questioning the scientific merit, we send it back to the researcher and say find three experts that say this makes sense. This committee is going to be that expert panel. They're not gonna say send it back to find three experts. They're also going to sit and actually do that piece. So to me, it's almost like a research committee, like a NIH section committee and an IRB. And I think that's gonna get really interesting and dicey and I always think we need to have two stages, but we're still working on it. We're gonna do ethical review, ethical review for the donors because I think that's what the donor is, is the ethical review. But we're gonna look at the risk to the donors and the recipients for all potential organs. We're gonna examine informed consent models because it's gonna get really dicey for the recipients as well, which I try not to go into necessarily today. And we also need to develop some sort of communication so that OPOs know what these research projects are and transplant surgeons know what these research projects are and ICU doctors know what these research projects are because right now there's really no central way to communicate and as organs are being flown across the country, you're gonna have, all of a sudden surgeons are gonna be saying, they're doing what in Chicago or they're doing what in New York? So we need some way to figure this out. OHRP has been multiple of our meetings and they just keep confirming, yeah, you don't have to worry about the dead donor. But we do think we need to worry about the dead donor. So who's gonna be on this IRB? Still up for debate? I get the first, I get to write up the first version of it. So this is my first plug at what the first version is gonna look like. All IRBs need scientists and non-scientists. So I've been told we have to have a representative, at least one representative from each of the 11 regions. I would argue we need two and then two alternates. And I think one representative from each region will be a scientist and one will be a non-scientist. The scientists will look at, they will be representatives from each transplant organ system. There will be a representative from the ICU. There has to be a representative from pediatrics because it's an IRB. The non-scientists, I think we have to have OPO representatives. I think we have to have donor families. I think we have to have recipients or families of recipients. I think we need to have an ethicist. I think we need to have a lawyer because all 50 states are slightly different in their rules right now, as I pointed out. So I think we have to have a lawyer to keep all 50 states rules straight. We have to have a prison representative if prisoners are involved and prisoners are involved. And we have to have a VA representative if any of this is happening in VA hospitals. And guess what, it all happens in VA hospitals. We have to have a VA representative. So that's a lot of people. So I'm seeing this as like a 30 member committee, which I think is gonna be crazy. Maybe we can do it with 24 because some of these people might be able to be two things. You know, I mean, technically, I can be ICU doctor and pediatrics and ethicist. I don't think I should be all three of those things, but I could. So we could have some doubling up. So I'm just gonna conclude for the donor stuff and open it up to discussion. Right now the consent really is an explanation of the gift. An acknowledgement of using the gift for research and education and is that sufficient? It's unclear what's most ethically appropriate and it's probably protocol dependent. And a central research review committee, IRB, can explore and improve these issues possibly protocol by protocol. I don't think we can set up something that's gonna work all the time. So I'm interested in comments. The scientists will look at, they will be representatives from each transplant organ system. There will be a representative from the ICU. There has to be a representative from pediatrics because it's an IRB. The non-scientists, I think we have to have OPO representatives. I think we have to have donor families. I think we have to have recipients or families of recipients. I think we need to have an ethicist. I think we need to have a lawyer because every all 50 states are slightly different in their rules right now, as I pointed out. So I think we have to have a lawyer to keep all 50 states rules straight. We have to have a prison representative if prisoners are involved and prisoners are involved. And we have to have a VA representative if any of this is happening in VA hospitals. And guess what, it all happens in VA hospitals. So we have to have a VA representative. So that's a lot of people. So I'm seeing this as like a 30 member committee, which I think is gonna be crazy. Maybe we can do it with 24 because some of these people might be able to be two things. You know, I mean, technically I can be ICU doctor and pediatrics and ethicist. I don't think I should be all three of those things, but I could. So we could have some doubling up. So I'm just gonna conclude for the donor stuff and open it up to discussion. Right now the consent really is an explanation of the gift. An acknowledgement of using the gift for research and education and is that sufficient? It's unclear what's most ethically appropriate and it's probably protocol dependent. And a central research review committee, IRB can explore and improve these issues possibly protocol by protocol. I don't think we can set up something that's gonna work all the time. So I'm interested in comments.