 We'll go ahead and get started with our presentation today. So Dr. Stagg and I are very excited today for the presentation. I know Dr. Rostro spent quite a bit of time arranging this as well. So Alicia, so thank you all for making that time come in today. I think today we have a really unique discussion and presentation to kind of go over. So it's kind of going to be a two-part thing. First we'll be Dr. Botkin on his topic of consent necessary for research with bioethics. And then after that we'll have an open discussion led by Dr. Jacobson with regards to some of the points that Dr. Botkin raises. So you can certainly interrupt Dr. Botkin if you would like to during this presentation. But we'll also have a very time for plenty of discussion for this afternoon so you can feel free to hold your questions till the end if you would like. To say that I feel insufficient to be able to introduce Dr. Botkin I think is a very fair statement. Dr. Botkin is very accomplished. As you can see from our notes in terms of the letter here he has a number of positions here at the university which he's a professor of pediatrics. He's also the chief of the division of medical ethics here at the university and is an associate vice professor or vice president for research here at the university. His expertise in this area at the university level is obvious but I think also important to know is sort of his national expertise in the area. So he is a former chair of the Committee for Bioethics for the American Academy of Pediatrics. He's worked with the NIH, their embryonic stem cell working group and has been the chair of that in the past. He's worked with the FDA and the Pediatric Ethics Advisory Committee as a fellow of the Hastings Center which is a nonpartisan bioethics sort of foundation and he's also served on multiple committees for the as a secretary advisor to the health cabinet. So his expertise in the area of bioethics is I think unmatched in terms of anything that we have here and I'm very excited for the opportunity to present it. Thanks a lot. Thank you so much for that introduction. This is a great pleasure and great pleasure to work with my colleague and mentor Jay Jacobson who's been so instrumental in my career here at the university. So I'm going to talk about a set of issues this morning that I think are some of the most interesting and conceptually interesting as well as important in the interface between ethics and biomedical research. So no external financial relationships that have anything to do with my talk today. So here's my objectives. I'm going to talk a little bit about federal regulations and some of the proposed changes in federal regulations that many of you may be familiar with that may come to fruition a little bit later this year. Talk about some of the challenges relevant to informed consent and then talk about what I think is a creative approach to think about our obligations and opportunities in this respect. Now these objectives could probably hardly be more boring and so again I want to emphasize that this is for the reasons I'm going to try to emphasize one of the most conceptually interesting and challenging areas. The proposed federal regulations that came forward last year were several hundred pages and half of that had to do with biospecimens and how we engage patients as well as research participants about use of their biospecimens. So here's a question that's going to frame the talk more broadly. Is it ethically appropriate for academic health centers to retain and use residual clinical biospecimens for research purposes? How much, and if we do so, how much should patients know about this practice? And further, should patients be asked their permission? So here's why this is particularly challenging. Research with biospecimens is removed in time and place from the source individual. The research regulations were written at a time where they had quite a few brilliant and experienced individuals who were participating in the development of those regulations that didn't anticipate the full spectrum of research, particularly as it has evolved over time. And most of those regulations are framed with the expectation that you would have the investigator sitting with the potential research participant and talking about the proposed protocol. You'd have an opportunity to walk through the basic elements of informed consent if folks would make a choice about whether to participate or not. So that direct interface is an assumption that is sort of baked into the informed consent pie, if you will. So biospecimens challenges that paradigm. You've got the biospecimens that may be acquired initially in a research context or may be acquired in a clinical context, and then they're sent off to a biobank. Somebody else is going to access those biospecimens and use them for research purposes that may not have been anticipated at the time that those specimens were acquired. So what does that mean in terms of the informed consent process? How do we engage people properly to get their permission to use specimens in such a fashion? So it's that distance between the specimens and the original source of those specimens that creates this challenge around knowledge and permission. In addition, there is no question a certain public sensitivity about the personal nature of biospecimens. And the proposed research regulations actually make a fairly significant distinction between people's data and their biospecimens with somewhat less proposed requirements for permission around use of data. I think a lot of us don't see that distinction, particularly because the data may well contain pretty highly sensitive information, where it's quite arguable whether you'll find anything of particular sensitivity in the analysis of the biospecimen. But yet there's this sense that this is a part of me supported by the research where folks have a greater sensitivity about how biospecimens are managed compared to how their data is managed. High scientific yield. This is a huge enterprise, the use of biospecimens, particularly in this era of genetic research, have proven to be extraordinarily valuable for a whole host of reasons. And low risk, and I'm going to emphasize this a little bit more here in a second. So the controversies focus for the most part on secondary uses of biospecimens originally obtained for other purposes. You have an opportunity to sit with a participant, you've got a protocol that you're going to be running, you're going to be a biobanking element, or a tissue analysis part of that protocol. You have the opportunity, obviously, to speak with folks about the use of their tissues and how that was going to play out in the context of research. So that's a regular informed consent sort of process. It's got its own challenges that we'll talk about, but for the most part that's fairly straightforward. It's the issues that arise when that biospecimen is then put in a biobank and used for purposes for which perhaps the original source didn't have a clear idea of what was going to be done because nobody had an idea of what might be done at that point. And then the secondary use of clinical specimens. People come into the hospital, they have tissue removed for one purpose or another that's used for its clinical purpose, but then it is stored by pathology regulations, but then maybe access for research purposes. Here is where we have an even larger gulf between what people understand is going to happen with their biospecimens and what may actually happen consistent with how the regulations are structured. So it's these secondary uses I want to focus on primarily. So the risk. Here's my claim. There are really no instances of welfare harm related to research with biospecimens. That's a pretty bold statement and we don't have obviously full coverage, full reporting system of the entire field, but in tracking this field pretty closely over the years, there simply are not instances in which there's been any significant breach of privacy or confidentiality or what I would call sort of tangible welfare harms. In other words, have people been injured in some concrete way by the conduct of this research? And I think the answer is for the most part, no. But yet there's this whole second category of concerns that we need to be sensitive to as well. There's a lot of dignitary harms here. Now in other words, people get upset when biospecimens are used in ways that they don't think are ethically justified. So there have been a number of cases where this has been illustrated. They have a supia tribal case. Arizona State University had a project with the Havasupai Indians who live in the Grand Canyon, a small tribe, high incidence of diabetes, and they acquired specimens after negotiation with the tribe to conduct research with diabetes, or at least as far as the tribe was concerned. The consent form had language that suggested that there may be a broader enterprise with those biospecimens. Nevertheless, the tribe understood that this was the nature of the research. Well, lo and behold, the biospecimens were used for a variety of other projects in the future. One related to mental health disease. And another that was particularly interesting was used for tracking the... What's the right tune? Evolutionary history, but the travels of... Where did the tribe come from originally? Fascinating domain of research has been particularly prominent in recent years. So these investigators found that, well, these individuals were from across the Bering Strait, Siberia. Well, interesting, but of course, the tribe has its own explanation for where its people came from. And it wasn't from Siberia. So they were particularly upset that the specimens had been used for a purpose that was contrary to the interest of their group. So even though the individuals in the Havasupai tribe were de-identified, their notion was that the tribe itself was harmed by virtue of the secondary uses of these biospecimens. And this is a particularly problematic area because our human subjects' regulations don't look at group harms. They only look at individual harms. Won't go through each of these, but the Moore case in California, there was a fight over whether Mr. Moore owned his specimens that the investigator had acquired in the conduct of research and then turned into a fairly lucrative commercial product. And Mr. Moore said, so where's my cut of the pie? This resolution of that case is why we have, within our consent forms now, consistently across the country, a line that says, we may develop a commercial product out of this research, and if we do, you don't get a piece of the pie, basically. A little bit better stated, but that's the notion. Henrietta Lacks' case. How many folks have read the Henrietta Lacks book? Great. Strongly encouraged for everybody. Not because I think it's the best depiction of how the world is or perhaps should be, but fascinating discussion that's directly relevant here. She had cervical cancer. That tissue was turned into HeLa cells, extraordinarily useful for an enormous range of research over time. And family, and of course Henrietta Lacks herself, were not aware of these secondary uses. The book is a little unclear what the claim is, but there seem to be some justice issues. Should this family have benefited in some way from the enormous enterprise that developed out of Henrietta's cells? New board screening lawsuits I'm going to talk about here in just a second as a particularly interesting and important domain that's raised these questions. So what are the federal regulations? If the individual source of a biospecimen is not readily identifiable to the investigator, the research is not considered human subjects research. If you don't know who you're dealing with, it's not human subjects. You're dealing directly with a person, and that's clearly human subjects research, but you can be dealing with their data or their biospecimens, and if you know who that person is or that person can be readily identified, then it's human subjects research. But the regulations were designed to say if you don't know who that is, then that person cannot possibly be injured by virtue of that research, and therefore we're not going to consider that human subjects research. So that's a pretty reliable standard. I mean, that's a pretty low standard. HIPAA is much more stringent with 18 identifiers. It must be removed to consider it de-identified, but the common rule standard in the federal rigs, remarkably low, and despite that remarkably low standard, we haven't had instances of harm. So why is that? That's probably a much longer discussion, but I think my bottom line is these things just aren't very valuable unless you've got a training to make use of those specimens in ways that can be creative. You know, this is not Fort Knox. A biospecimen bank is not Fort Knox. It's only valuable to people who have the expertise to use it. So identifiable specimens, if they are identifiable, then consent can often be waived if an IRB determines that the criteria are met, and I'll show you what those waiver criteria are. Similarly, consent can be simplified or altered if the research meets the waiver criteria. So a lot of choices for investigators and IRBs in this particular domain. De-identify them, then it's not human subjects research, or if it's identifiable, make the claim that you've met the criteria for waiver. Excuse me, here are the waiver criteria. You have to fulfill all of these, and if you do, you can waive foreign consent or simplify it. It has to be minimal risk. It will not adversely affect the rights or welfare of the subjects. Nobody's quite sure what that one means. Not practicable to obtain consent, and when appropriate, subjects are given pertinent information after participation. So, it's really the minimal risk and the not practicable that are the two key ones in this particular domain. In general sense is, if you've got 500 biospecimens that you've collected over a 5 or 10-year period of time, is it feasible to go back to those people and get their permission for some future research project? Generally, the investigator in the IRB will agree that's just not practicable. And you could try, but the burden to the research enterprise would be so great that it's not appropriate to do so. So, waivers are really pretty easy to get in this particular domain. Again, if you're using identifiable samples. So, here's a particular question. I'm framing down to this particular debate, and this is where a lot of our own research has been going forward in recent years. So, is it ethically appropriate for state health departments to save residual blood spots after newborn screening for biomedical research purposes? How much should parents know about this practice, and should parents be asked their permission? Okay, so one subset of this larger debate. So, here's what happens across the country at this point. In terms of what state health departments do. So, folks, I think this little maybe outside your domain. So, in this day and age, every baby that's born within the first few days gets a heal prick and blood spots obtained. And more than 30 different conditions across the country then are evaluated for early diagnosis and treatment as part of the newborn screening process. So, there's almost always residual blood left over. So, here's what states do with those blood spots. This one, if you can't read it, is one to six months. So, that's pretty much long enough to do your clinical tests and then you don't save them after that. If you save them longer than six months, then chances are pretty good you're saving them for some other purpose. So, you see increasingly long periods of time and you've got six states that save them indefinitely. And these are some of the largest states in the country, including California and New York. So, a fairly large percentage of babies in the country have their blood spots saved for decades. So, what do people use these things for? A variety of purposes. Probably the single most common use is for quality assurance purposes. Particularly the positive specimens are very valuable when you're trying to develop new screening platforms to have true positives and true negatives extremely useful for that purpose. Forensic purposes rare, but sometimes this is the only specimen left for a baby who's died and you can match remains with the baby's original specimen. Or sometimes you have a first child that dies and maybe the explanation is SIDS. Second child comes along with a heritable condition and they say, ah, maybe we missed the diagnosis that first time. Let's go back to that blood spot from that first baby do an analysis and find out whether in fact there was a heritable condition perhaps it was the explanation for that first death. Again, unfortunately those are rare. Biomedical research is the main one and the main controversial one. Genetic epidemiology how common are certain variants within the population. Myriad access Utah's blood spots and a de-identified passion back in the 1990s and asked the question, how often does BRCA1 mutations occur within the Utah population? Pretty interesting de-identified blood spots, but now got an obvious ethical issue there. You've identified babies who have a BRCA1 mutation and a future risk of breast reverian cancer in a family that presumably shares that variant. De-identified so nobody pursued that, but interesting. It illustrates the that particular use. Looking at metabolic disorders, endocrine disorders that are focused on newborn screening. Infectious diseases. Mothers and babies share the same environment. The HIV epidemic is a good example of how these biospecimens were used early in the 1980s in New England to say, so how many women are infected with HIV? And what types of women are these? Are these urban populations? Are these suburban populations? And how is it developing over a period of time? You've got those blood spots saved. You can say over the last 5 or 10 years, here's what we're seeing in terms of the incidence of HIV in the population. I suspect what we're going to see within the next few years is that these blood spots are going to be extremely useful for following the Zika infection in pregnant women. Very useful for that and also toxicology. Again, baby and mom share the same environment. You can measure toxins, potential toxins that are transferred from the mother to the baby project around the Great Lakes that looked at mercury in babies with mothers who live next to the lake versus those who lived further away from the lake with the notion that if you live next to the lake, chances are you're eating more fish. And as higher fish consumption leads to higher mercury exposure for babies. And indeed that was found to be the case. So there's a whole bunch of things you can do with toxicologists. You can see how useful these things are. We're currently doing a literature review. We've identified so far 2400 studies published literature using dried blood spots and when we finish with this project we'll have a breakdown of what those uses were over a period of time. So newborn screening dried blood spots. What do parents know about this? Nothing. And that's because newborn screening itself is conducted as part of a mandatory state program where parents are not asked for permission. There's some degree of notice and the ability for parents to opt out but for the most part folks don't know that they can opt out so they don't do so. So newborn screening itself is conducted without parental permission so there's no vehicle by which folks are effectively informed. Newborn screening brochures may have a sentence in here that says the state may save these and use them but when you've just had a baby are you reading all the brochures that are provided to you in the bottom of the bag? Of course you're not. Not dissimilar for example for the admission agreement to the University of Utah that does have a line in there whether it's 10 font or 11 font that says we will use or dispose of the residual samples in a manner consistent with state or federal law. Well okay we've informed our patients about what's going to happen, right? Similarly nobody reads that nor if they were to read it would they understand what that means. So research with dried blood spots is almost always conducted with de-identified spots though and therefore it's no longer human subjects research. Many states do have the IRB look at it anyhow because it's a somewhat sensitive domain. So here's what's happened. The public got wind of this and made t-shirts help. The government has my DNA and that's how it was portrayed of course. The government, the state is developing a DNA biobank on the state population and as you can imagine a lot of folks didn't think that was a very good idea. So two lawsuits were brought both in 2009 both interesting on their own BACIS Minnesota's suit was based on a state genetic privacy law that said if you're doing genetic testing you need to get informed about how to do a genetic test. Well parents said newborn screening or secondary research biospecimens that's genetic how come you didn't get our consent. Court initially said well newborn screening is different covered with different set of laws but ultimately the public pressure was such that the complainants won that one. Texas was brought on a different basis constitutional claim of illegal search and seizure. You're taking this stuff and you're using it for purposes that I don't know about without my permission as a parent that's unconstitutional. The state hustled to solve this or resolve this out of court because you can be sure that the state did not want the court to come forward and say secondary uses of biospecimens without permission is unconstitutional. We understand what an effect that would have on the research enterprise. So both these suits were pretty complicated but for the most part Texas ended up destroying 5 million samples that they had retained over a period of time. So what happened? Newborn Screening Saves Lives Reauthorization Act people have been waiting for this for a while federal legislation provides resources to help states with newborn screening in a variety of different ways. So this was reauthorized in 2014 and literally at the last minute there was an additional provision 12 stuck into this law and I don't have his common knowledge that this was Rand Paul who had worked to insert this and he's got a libertarian perspective and this sort of reflects to some extent the sensitivities of folks from a more libertarian perspective. So research it says research with newborn screening without spots is human subjects research whether or not the spots are de-identified. So this whole business about de-identifying and getting outside the regs is no longer active and waiver of parental consent for research use is not permissible. So all the criteria to allow waiver are specifically invalidated with this law. So what does that mean? Any secondary uses for residual biospecimens in this context needs to be conducted with parental permission. And as I'll show you that's pretty consistent with what the public wants but I'll also tell you that this landed with a bombshell on newborn screening world. It is simply arrested research in this domain because of the lack of infrastructure to get parental permission for these uses. So very difficult to implement a new consent provision because we're not getting consent for newborn screening itself. Now postpartum period is not the best time to, I mean there's a lot of bad times in medicine to try to get consent. This is one of them. Postpartum period, short, hectic other priorities. People are worried about other stuff. Appropriately. The consent process is likely result in a substantial decrease in available dried blood spots for research. So Michigan now has a Biotrust where they get informed consent for the acquisition of newborn screening blood spots in secondary research units. Their uptake is just about 60%. California when they made a transition in their newborn screening program to adopt tandem mass spectroscopy as a infrastructure tool was required by the IRB to have an informed consent process. Their uptake was also about 60%. Now is that because 40% of parents are saying no? It's not. It's because a large percentage of people aren't being asked the question. The staff and the nursery are too busy. It's not their thing. Research is not their thing. They got clinical care to provide. The secondary consent process is an extra burden and extra workload. And many individual nurses, many units and many whole hospitals said we're not doing it. Now if that 40% dropout was random in the population then 60% you probably still have a good sample set. If it's not random and you have certain communities that have decided not to participate then you really lost the fundamental value of this specimen which is that it's everybody. Right? All geographic locations all racial and ethnic backgrounds etc. This is a serious problem at this point in this particular domain. So we're seeing this values conflict between our normal understanding that permission for research uses is foundational important. But yet we see that that process so severely affects the research enterprise and the infrastructure developed that it may invalidate the research that is being proposed. So how do we resolve that dilemma is sort of the key issue. So in a similar vein the notice of proposed rulemaking came out this last year. Comment period ended early this year and the Health and Human Services the Office of Human Research Protection is working hard to try to get the final rule out by September of this year. So we may well see before the end of this year changes in the federal regulations that have been in place for 25 30 years or so. So this notice of proposed rulemaking proposed to extend the definition of human subject to biospecimens again whether or not they're identifiable. Broad consent from individuals would be necessary before biospecimens could be used for research and this is for specimens acquired prospectively. All the stuff we have in our bank wouldn't be impacted it would be prospective acquisition. Broad consent what they mean is you ask folks some general questions we're going to we would like to do research in the future with your specimens we don't know what kind of research that is is that okay with you. Now maybe it's a little bit less broad than that maybe if you're acquiring specimens in a Huntsman Cancer Institute you would say we want to use it for cancer research maybe in this domain we would say we want to use it for investigating eye diseases but the notion is we don't know what we're going to use it for so do we have your permission to use it for stuff. Similarly the criteria for waiver would be quite limited under this proposal so this too would change how we approach this whole domain and again emphasize not so much an issue with the research context where you have an opportunity to ask folks you know can we use the stuff for other purposes in the future but the clinical context and this would say that patients coming through your system would need to be asked their permission for secondary uses of biospecimens and if you don't ask if you don't have it documented yes then those specimens are not available I want you to think about what the implications would be for the research that's being done in your domain. So here's my summary of the literature. Longer talk we could walk through some of the studies but I have to trust me on for the most part the study's been remarkably consistent here the majority of individuals when you talk to them about this support secondary use of biospecimens people get it they say I understand I'm supportive of research and particularly patient groups understand this people want to know but people want to know about it right doing this stuff without any transparency is not acceptable to people and people want a choice just ask me I'll say yes but I want you to ask me I want you to ask me and what the literature also shows if you ask them on an equal basis there's different ways we could ask you one would be to say we want your permission and we need you to sign this form in order for you to be in or you can have an opt out system which says here's how the system works if you don't like it let me know and you'll be out and as you might guess opt in tends to have a substantially lower uptake and opt out there's a professional group Christine Grady who runs the bioethics program at the NIH put together a group of folks to look at this set of issues I was part of that group but I didn't sign on to the final statement for reasons that I'll illustrate for you in a second but their question was is this broad consent ethically appropriate and their workshop participants in the statement they published this last year said the broad consent for research use is ethically permissible and in many cases optimal when it includes the following components initial broad consent a good process of oversight and approval and when feasible ongoing process of providing information or communicating with donors I think this last one is particularly relevant to sort of smaller shop type of circumstances if you've got a particular clinic with a particular set of patients who are coming through on a regular basis then some sort of meaningful longitudinal communication is a little easier than in other contexts so this is what they had to say they like the notion of broad consent so as I mentioned the OHRP where the feds put forward this notice of proposed rulemaking there always is a public comment period so they got public comment and then they're going to publish the final rule later this year well here's an analysis of the public comment as of a couple weeks ago more than 2400 comments received that's a huge number anytime you propose federal regulations you get a smattering of people who comment this is enormous people are very interested in this issue so 2400 with specifically on the biospecimen stuff this was what folks were most concerned about in these proposed changes substantial majority of commenters oppose these proposals and this is what this is how OHRP itself describes this most comments were from patients in the public opposition across all subgroups patients opposed it the general public opposed it and research affiliated organizations proposed it opposed it now what's interesting is they opposed it for different reasons so it'll be very interesting to see how they come forward so here are the reasons what were the patients concerns well patients and I think what we mean by patients in this context is advocacy groups for patients with one disease or another didn't like this at all because they thought it would slow down research which it will they like the research enterprise they understand that this is important for making progress with their disease in contrast general public and Rebecca Skloot who wrote the Henrietta Lacks book published an article in the New York Times before the end of the comment period that said hello folks be aware this is coming if you're concerned write the feds and there was a wave of comment after that New York Times article well the general public was somewhat more supportive even though the general public opposed it in general but opposed broad consent and any waiver of consent so their notion was we want to know exactly what you're doing and we don't think you should be able to waive consent talk to me so completely opposite and then research affiliated individuals overwhelmingly opposed and really on the basis of several arguments enormous complexity of the tracking decisions and we tried to think this through certainly from the University of Utah over the last couple of years how would you set up a process where you would have a database that would track every patient that came through the institution and what their choice is understanding that a lot of people come in multiple times and they may well change their mind or not sign the form this time when they signed it a month ago if you don't sign the form then you're out so extremely complicated tracking mechanism very expensive lack of risk of biospecimen research we're not talking about stuff that's dangerous and really this is a central ethical concern the lack of a meaningful consent versus broad consent now particularly if you're offering this to everybody who walks through the institution it will quickly collapse into what a lot of us perceive the HIPAA process to be sign these forms and the doctor will see you you know in 20 minutes or so nobody reads this stuff, nobody understands it but you get a signature and what the federal proposed federal regulation said once you get that signature you don't have to have any sort of IRB oversight there's no oversight left at all you can do whatever you want with those literally whatever you want with those specimens so the advisory committee on human research protections is an advisory committee to the secretary of health and human services about the whole range of human subject protection legislation I currently chair this so I had the opportunity to work with the group to prepare the statement on the NPRM we oppose the proposals regarding biospecimens for these, for this reason subjects would not be sufficiently informed to make a knowledgeable and educated decision about participation in undefined future research while researchers would rely on a vague broad consent to conduct unfettered, unsupervised and unlimited future research on subjects, biospecimens and data so one might expect we said therefore that broad consent would be less a commitment to individual autonomy than a license to researchers for unfettered use so here's the challenge and I'm going to take a step back here for a minute to talk about informed consent general and how we might approach this issue so you have full informed consent with the form up here, this is the sort of ideal maximal engagement, you could have broad consent so less specific information with the form, you could have a simplified consent form, a simplified consent process with or without a form and now all the way down here you got waiver informed consent which of course isn't informed percent at all, it's nothing so here's the domain that I'm interested in thinking about, do we have an opportunity to think about other ways to address this issue in that particular context, so let's talk about informed consent and specifically the issue of comprehension it's intrinsically difficult when I came to SACARP as chair now four years ago this was going to be my mission to try to improve the informed consent process because everybody recognizes that it's seriously problematic, people call it broken and I think that's not an unfair but it turns out it's actually very hard people have very poor scientific literacy the general public I'm talking about they don't know about biomedical subjects highly variable literacy in general and highly variable numeracy of course being how people understand numbers you say something simple like 10% of people might have this adverse you know, 10% people don't understand what that means, a lot of people don't content is difficult for investigators to simplify it's part of our acculturation process to lose the ability to frequently talk in normal people speak and it's much easier with your consent form to kind of take the language from the proposal and kind of plunk it into the consent form and you're good to go forms are crafted with limited attention to comprehension that's not a priority long high reading levels dense limited use of graphics these are all how our consent forms are structured and the IRBs do not push back and force people to use what we do know so what do we know and I'm going to show you that in a second so I think there's few incentives for any of the stakeholders to improve comprehension other than the research participants themselves which of course are a pretty key stakeholder but the claim here is sponsors investigators IRBs all gain benefits and avoid burdens through high complexity there's simply no effective pressure within the system and part of that is the fact that my efforts with SACCARP to try to make a significant change here have failed and part of that failure to some extent is just pushback but it's also the current regulations actually don't require people to be able to understand they require you to say stuff to folks they don't require that they understand what you said and so there's no hook you put out a 40 page consent form at a graduate school level there's no way the feds to come in and say we're going to cite you for non-compliance because you've got a lousy consent form there's simply no hook to do that now the new proposed regulations have one line in there that says consent process will be done in a fashion that is understandable to research participants so that one line is going to be a hook for actually forcing some change down the road but here's one of the hooks despite extensive evidence that research participants often have a very limited understanding of key elements of research people agree to participate anyhow so this problem with comprehension would have been solved a long time ago if folks were of the mode to say I have no idea what you just said I don't understand what this research is about why would I sign up with you they don't say that they don't understand but they sign anyhow so we allow research to go forward with often a modest level of understanding so what have we learned over the years there's been some good research although not enough revising forms for simplicity and processability and graphic presentation does show some efficacy it's not revolutionary but it helps use of multimedia tools is promising but also not dramatic teach back and one on one discussions are promising so teach back is where you say I want to understand whether I was communicating effectively with you can you tell me what you understand to be the risks of this research participation or tell me what you understand the purpose of this research and if they don't get it right then you readdress the problem until they understand this is good therapeutic misconception I won't talk about but it's a serious concern this is where people misconstrue research intentions for clinical intentions they think they're allocated to one research group or another because that's what their doctor think is best for them as a person but really the whole issue is why people agree is for trust and that's true probably both in general clinical realm trust is central if they trust you as an investigator if they trust University of Utah Moran Eye Center then they're likely to agree whether or not they have a real understanding of what the enterprise is about so that's a good thing to a certain extent it's not a good thing if in fact you don't deserve that trust so obviously incumbent upon us to deserve the trust that people place in us so what should be the nature of the informed consent for the clinical context for secondary biospecimen use so again I'm interested in this issue of what we do with people who are coming through for clinical care and we're going to use their specimens for biospecimen use if we want to get consent for that it's a large new commitment of time and who's going to do this you know people at the front desk are they the right people to engage in this conversation you got to have knowledgeable staff it's really a low priority people are concerned about their health they're coming in here for other reasons this is not a priority either for the clinicians or the patients need for large investment in tracking database and a complete lack of risk so given these facts or at least perceptions of reality what's justified what should we be doing here so informed consent obviously a foundational principle first one in the Nuremberg Code part of the Belmont report respect for persons and what Faden and Beecham has said as we need to be thinking about consent as intentional with understanding and without controlling influences but what if this autonomous authorization is really not a realistic goal can we define more limited goals that permit research when fully autonomous authorization can't be achieved particularly from a full understanding standpoint some other different ways to think about our obligations to sources of biospecimens so here I'm going to rely on an interesting proposal or set of ideas by Frank Mellon and Albert Wertheimer that they articulated a couple years ago it's called the Fair Transaction Model and what they say is the criteria for assessing the validity of consent transactions should be based on fair terms of cooperation for the respective parties that reflect the contact of the activity so they want to focus on both sides of that agreement not just how much do people understand but what's fair in terms of both sides of the agreement what fairness entails they say well very reasonably depending on their risk benefit profiles presented in the clinical trial so if you're doing chemotherapy if you've got a phase one chemotherapy trial you better have high expectations for understanding for the individuals because they're making a very serious and potentially life threatening commitment on the other hand minimal risk research accordingly would impact what your obligations are for low risk transactions they use the example of signing forms for mortgages and car rentals and software purchases I mean how many times a day or a week do you click through a consent agreement you check into a hotel in order to get online you click through their agreement anybody ever read one of those no why is that okay and would it be reasonable for me at a new hotel to call down to the front desk and say I'd like somebody to come up here and explain this consent form for me and I want to understand what the risks and benefits are of my joining your system right nobody expects that to happen and nobody's built the infrastructure to do that but yet somehow we feel okay about that why is that okay now legitimately you might say somebody really ought to be writing this in ways that I could understand if I wanted to but for the most part we feel okay about checking through those things and what they claim is that indeed that is a legitimate transaction but it's heavily dependent on institutional protections that justify these agreements to begin with I mean I feel okay about clicking there because I don't really think this is a high risk enterprise because I have a certain amount of trust that there's been checks and balances elsewhere in the system that are protecting me so in this particular context it seems to allow for a limited disclosure of information when the risks are low institutional protections are in place seems to allow for a limited or no assessment of whether people actually understand what they're signing up for secondary research biospecimens extremely low risk low burden for the sources and good institutional protections in place high scientific value highly burdensome system to actually obtain fully autonomous authorization if you could do it it would take an enormous enterprise so the conclusion would be a modest level of authorization acceptable no assessment of comprehension is probably accessible but a complete lack of transparency is not and I think where we as an institution and I'm thinking broadly of not only University of Utah but really all of the biomedical enterprise we don't let we don't tell folks what's going on they have very little opportunity to sort of understand what happens with their biospecimens or data etc so there's been almost a complete lack of transparency there I think where again this proposal is going to go into that space here's what sacchar proposed with relate related to biospecimens recommended a requirement for provision of notice of research practices let folks know what you're doing with an opt out mechanism no signature required allow people to exercise their opt out rights I mean it can't be some Byzantine telephone system that works on Tuesday mornings to allow people to opt out you have to give them some legitimate level of choice and you track people who opt out you don't have to track everybody you track that small percentage of people who are concerned who do care who ask some questions and say this isn't for me fine and you're not going to we're not going to wave that opt out if they've opt out they're opted out so still requires for investment in institutional tracking but at least theoretically far less than an opt in so I think the notice an opt out approach promotes transparency and choice but the ethical justification is contingent upon a real effort to do this in the right way the problem with notice an opt out is that you can put it in a brochure right that sits on the clerks desk and say okay we're done we told people well in fact you have it so you really need to make a legitimate effort to try to help folks to understand I think this approach is appropriately calibrated to level of risk and the challenges of actually obtaining a fully autonomous authorization here so we did a focus group couple years ago series of focus groups around the west here specifically on this issue the university was thinking at the time and still is about how to approach this issue so we did 12 focus groups which is pretty robust for a focus group study we told them what happens in this day and age with respect to access to their records for research purposes and what happens to secondary biospecimens and of course folks had no idea it's like well I thought my record was in a chart in my doctor's office and I thought they I didn't know what they did with the specimens I kind of sort of thought they destroyed them after they used them so you tell folks this stuff and it's like wow okay that's a big deal but you also tell them what's been the national experience in terms of risk and also that there's institutional safeguards in place and this notion that if you have a research project you have to go to this group called the IRB in order to make sure that that research is being conducted ethically and folks say well that's a pretty good idea that's a good I like that that's reassuring when folks learn that kind of stuff which they of course don't know so large majority of participants supported this opt-out we said here's what we're thinking about so we phrased it a little bit differently we didn't say you know all other things being able to prefer opt-in opt-out we said we'd like to do the notice an opt-out approach would that be acceptable for you as a user of the system and folks said yeah as long as you tell me as long as I have a choice that's fine seem to be there we go so conclusions Consent with biospecimens represents really important and interesting and truly problematic conflict in values we do want to respect people's autonomous making decision we know people do care about this or many people do we also want research to go forward it's a legitimate clash in those values Bates relevant to other contexts where we're using stuff away from the bedside data not much difference with data and biospecimens but there's big data studies cluster randomized trials a lot of interesting areas where it's very difficult to get individual consent I think notice an opt-out may be inappropriate when the risks are low and institutional safeguards are in place but we need more innovative ideas we need more research in this domain we need to figure out how better to do what we really want to do which is make sure folks are adequately making decisions about this aspect of their health care alright stop there so thank you so then next thing Dr. Jacobson if you want to help now we thought we have about 30-40 minutes left we had a discussion and I think there's probably lots of questions that people had I think Brian and I had an opportunity to review Dr. Bakken's slides ahead of time and there's some things that we thought of and obviously we're interested in what other people thought I think from your presentation and I think one of the more interesting discussions is for me personally is the question of sort of the opt-in versus opt-out consent process I'm concerned with the opt-out that like you said there's got to be mechanisms in place to make sure that that's actually effectively done and I think in a lot of places that would be ineffectively done which I think some people may have a concern with but I think you're right if you have an opt-in policy it's harder to track I'd be interested to see potentially what discussion points may come from that the other thing that I'm thinking about sort of bioethics and sort of different things related to there's sort of the four quarter stones that we always talk about which is autonomy, justice, beneficence, non-malificence and I think you raised a very good point that most of the biospecialist research has been really individual non-malificence that's been shown I think the question most interesting to me is this concept of autonomy and if you have de-identified data is that then considered not to be human research and so thus you don't really have autonomy concerns because it's no longer a person's actual specimen so I'd be curious about Dr. Jacobson's discussions about that as well I don't know if you had anything else Yeah, so we were just hoping to kind of Russ and I, our role is just to present the issues that we thought of and then Dr. Jacobson is going to help kind of facilitate a discussion the way he does so well and so a couple points to Russell have thought of Dr. Jacobson So another important consideration here is the needs of the general society and a case in point which is recently published and these are people who have gone through very broad databases to try to find out individuals who have clear genetic risk who are dominant or they are both side recessive dual recessive there should be 100% incidental disease and have no clinical disease and they have come up with these they're calling them superhuman superhuman people and they have found that there are these people out there clearly should have awful diseases and all the events they have and they should have had about a time they have the blood but it's all de-identified and now they can't go back and find those people and these people I think are incredibly valuable and they're tearing their hair out from hundreds and hundreds of thousands of specimens and here society has also a need in association with now we can't easily go back and find out what these people have that potentially could be a treatment of awful and just barely come out it was actually listed in just last week's Economist about this effort and that's the big single thing the thing to do for exciting work so there's a society societal side to this that also loses out and that kind of goes along with I thought one of the interesting things from your presentation was that the group that was really in support of the proposed regulations because they wanted fewer regulations were the patients who want more research to be easier and I thought that was really interesting and kind of highlights that we can benefit from research well we found this in our own research with the blood spot issue we did a large national survey of just general public attitudes and again a lot of folks were very supportive but they wanted to know about it and wanted a choice we then took a second and much smaller group of parents kids with parents of kids who had had leukemia and parents of kids with PKU one of the conditions of course on a newborn screening panel and asked them the very same set of questions and as you might guess they were much more supportive of research the first group was supportive this group really got it and so once you've had a disease experience in the family then your attitudes changes but that group actually had pretty much the same group of attitudes and privacy protections as well so that piece seems to be a core interest Dr. Morris I'd like to hear Dr. Barton's comment about Dr. Olson's recognition of the community Ruth Layton and their colleagues have written recently and claimed that it's not fair for people in the community to be freeloaders in other words to participate in the reception of the benefits of medical research but not to contribute to medical research to freeload because their neighbors in the community have participated in research we've learned better how to manage patients they now benefit from that new information but they're not they're not engaged that's directly linked to Dr. Olson's comment about the community obligation well there are I wouldn't say a strong theme of communitarian philosophy out there within the U.S. system but that's an entirely legitimate approach and some of the members of our SACARP committee wanted to very much push that exactly that notion all of us have benefited from people's contributions to the research enterprise in the past if you're coming to an institution like this you're benefiting from what those folks did it's your obligation to contribute to that enterprise in some way that if the risks are in fact very small I mean you don't have a big obligation to put yourself at risk but in fact the risks are extremely small and there's good safeguards in place you have an ethical obligation to contribute to that and therefore we're going to take advantage of that obligation and not necessarily talk to you about it or ask you about it the question is whether that I think can be ethically justified but it doesn't fly very well with the general public the general public doesn't so much say they don't get that piece they do want to know about it and they do want some choice about it so I think that it would be an uphill climb over time to try to reestablish the research regulations on a more communitarian basis and I would say that there's a bit of a black history going against two not too many years ago the notion was well you're a charity patient at our institution you're going to pay us back by being a research participant and we're not going to tell you about it but we may well apply substantial risk I mean that was common terminology in the 50s even into the 60s so we got to be guard against that sort of abuse of that philosophy as well Jay maybe you can ask with my add a chair and be available for commenting and questions I don't try to drive those let me just pop up here for a minute and say first of all I'd like to nod to Jeff and say what a lovely job that was covering both a very long and complicated ethical and legal history we both have a colleague piggybatten a philosopher who reminds us that what we call hard cases in ethics often are cases where there's one ethical theory that drives one conclusion and another valid ethical theory which goes in exactly the opposite direction and I think that Randy's question and Alan's follow up kind of remind us that two very big theories about what is right are in conflict here the first one is very very American this idea about autonomous choice is a principle based theory with huge weight on the principle of autonomy the way to think about what Jeff talked about is to think about how this looks for example across cultures not all cultures value autonomy or that principle as much as we do and we'll ask you to talk a little bit about that in other places the other one is to think about the ethical theory called utility or utilitarianism which gets a little closer I think to the idea of weighing the community's interest what's best for the most as opposed to what does one individual choose where choice is so important and I think when you think about the scientific enterprise we tend to lean toward that utilitarian approach right the things that we're looking at many of us are clinicians but on the research side our goal I think is to improve things for large numbers of people and we think about the results of our research that way that is the research that makes a difference for a large number of people tends to be more exciting and more compelling than something that might affect the single individual so as soon as we begin to weight the consequences to the many think about the topic that Jeff is talking about that is if you look at risk benefit what you utilitarian would do add up the harms and add up the goods that are included it's really hard to find any individual harm from research on things like blood spots or retained specimens on the other hand if you look at the collective benefit it gets bigger and bigger over time it's almost unbounded as we can't fully describe it but a utilitarian would measure real consequences that are observable and the weight tilts tremendously toward the general benefit of so much greater than the individual harm I mean it's not even close so you have to really look at what the claim is for harm and the claim I think rests around that tremendous value in our country of autonomy and individual choice and another one which is kind of a more recent value which is this idea of privacy a constructed value it's not a constitutionally main principle but Americans care a lot and the T-shirt tells a really big story the last thing that I wanted to say is that I mentioned looking broadly how does this look in other cultures the other one is over time and I think that and again Jeff mentioned on one of the slides that lack of trust or having trust in a body is a critical element many of you I think can appreciate that in our lifetime a huge erosion of trust in institutions and particularly the government so I think you just want to recall all of the things that kind of government does that went unresisted for so long for example a draft where there's no opt out there's a government choice to take not just your tissues but your whole life and put those at risk and the counter argument is for the benefit of the larger society so there's an argument where you have government control of much more than a blood spot but we haven't seen that for a very long time and I would gamble that there would be more resistance to that in the 21st century than there was in the 19th or the 20th so I think those are really important background issues and I see this issue as a very American issue and the argument about insufficient trust in government that is when you talk about the child's DNA isn't that interesting the government also has the child's birth certificate in terms of data we do know who that child is and there's often a fingerprint on the birth certificate so we actually have a lot of reliable data that people haven't focused on but I think that the kind of confrontation between genetic technology which is very confused in people's minds in terms of what it identifies and this idea of government distrust has really kind of combined to make what in many places I will argue would be a trivial issue that is I think there are many cultures that would have no controversy over the goodness of the identified and learning things about the public but those are just kind of across and vertical ways of looking at this problem Jeff what about that across cultures you have colleagues internationally how does this look in other countries yeah that's a great question and I think that the fact that the biomedical world is in such close communication we all publish in the same journals it's probably not as as large of distinct differences in other cultures as you might guess on this particular issue I do think the dialogue is different and where I think other countries have probably done a better job than we have done or probably could do is with the gauge of the community in other words the notion might be so how do the English people think about this particular enterprise and I think sort of crafting ways to go forward is a more comfortable way within those societies to say we've done due diligence we understand what the public has to say and now we're crafting this national policy accordingly here it's a much more Balkanized or atomized sort of system where you would have to engage your local community and you have to pay attention to those small number of voices in the community it might really have something different to say so I think here we're more sensitive to making sure that there's individual choice even for those folks who tend to be at their particular point of view so Vanderbilt would be a good example they did a wonderful job with their bio view that engaged the community over a period of time in a very robust way and acquired community feedback they have a very high stature within the community and they set up a system that was a notice and opt out that functioned quite well with very high levels of engagement so they took seriously that sort of community engagement the way I think a lot of the Europeans have done interestingly though I think the Europeans probably have a higher degree of concern over some of the privacy issues than a lot of US folks do for some reason the privacy issues have been very prominent in that particular domain and have restricted some of the otherwise communitarian sort of philosophy that may be part of those societies more generally yeah I just had kind of one question and just observation and I felt like throughout your presentation you talked about how the general public actually really has kind of a similar opinion for it and I got the sense that that didn't really vary so much by you might guess that it would vary by political background or ideological background but it sounded almost like the public is pretty much in consensus that they want to know and that they want to be informed they need informed consent and all of that is that your observation or does it kind of vary well actually one of the interesting things we did with our large public survey 3,800 folks across the country on the newborn screening blood spots we worked with our political science department here at the university and got measures of political background religious background of course we had race income that sort of background as well and probably the single biggest predictor well it was a single biggest predictor of concern about the access to blood spots was a conservative political philosophy so those sorts of things are relevant we did not find that race or income or education level ended up having much of an impact it was really political philosophy that ended up having the most significant impact so you're right a lot of times when we talk about you know overall 80% of people think this is a good idea well you break down that 80% the 20% and those are different people in ways that you can sometimes describe one of the things that I think is so interesting is that if you don't ask you don't know and if you do ask you can't always predict what you're going to learn a relevant connection to this I think is if you think about garbage so we know that in the computer language of garbage and garbage out right a lot of us I think might think about specimens that are harvested from patients as garbage that is they let go of them I think the blood spot is not a bad example that is if the sheet was soiled right with a drop of blood you throw that away and nobody actually asks questions about the drop of blood on the sheet so I think a lot of us actually could be modeled that way and it looks really differently but watch what happens if you were to ask people can we investigate your garbage can we look through your garbage for things that might prove valuable many of you must know that there are archeologists who actually do this and it's a fascinating model because what they find often by large communities is very useful information about people's behavior right so if you went to people and said we're going to use your garbage to do something that would be very valuable in the long run to the community how do you feel about that I will speculate then in America you find a significant number of people who would say I really like to know who's looking through my garbage and Jeff didn't talk about money very much in this presentation but you want to remember in the background particularly the more case when somebody's making a lot of money of something that you discarded that has no personal use to you at least again I'll speculate a lot of people in America would like a part of that so I think the garbage stories are really interesting when you look at and here just a couple things because common law has to deal with all of these things garbage and blood specimens or tissue specimens so somebody finds a ring in your garbage is it theirs so just kind of think about that for a little while what the courts have done is just fascinating the details are always important well if you threw away the ring you were angry this is a marital discord and a ring hit the garbage right you threw it away it pretty much belongs to the finder right as soon as you say it was an accident or I didn't know that you know it was going to wind up in the garbage there's at least a debate and that goes on and it wouldn't matter if it was de-identifiable that is if the finder melted it down I think there still would be a fight so the fact that it's not identifiable as you're already probably less important the key is around value and who owns what there are actually some famous cases about garbage where a movie script was thrown away and the person who discovered it knew they had something really valuable here and an argument ensued eventually this showed up in law and it was decided that it was in the garbage not because the owner of the script threw it away but someone who wasn't authorized to do that with the script did so so that became relevant so just kind of going back to the idea of consent European countries and other countries have dealt with organ donation you want to think about that it's very much like tissue it's organized tissue and so there are places that have this opt out phenomenon that Jeff is talking about where the greater good is an argument over things like autonomy and choice that as so many people could benefit from the organs that are available at your death that people have made the choice of saying let's assume that people have agreed to do that ours is quite opposite and again it's a very relevant analogy that is now the source of the tissue is dead but we still fight about the idea of autonomy even as a surrogate so even in this country where people have decided to donate their organs when family members are resistant to that more often than not to be acknowledged now let's hear some of your questions I think it's really important what you were saying about education and community engagement I think the people do want some research done I think it's really difficult this is even coming from some of my own personal experience organ donation to opt in or out during a really stressful hospital setting I think it would be amazing it sounds a little strange but if we could educate people more even like in high school biology classes have a little bit of a blurb or a little bit of a time where kids study about research and learn about issues ethical issues about tissue donation and I think it would be amazing organ donation being tied in driver's licenses if people could be educated and maybe given a chance to opt in not to just organ donation but tissue usage with a driver's license you have that opportunity now when you're checking into a hospital you would be able to show or scan in the future of your driver's license and say what your individual wishes are something like that could be done I think the public wants to be educated and maybe something like that in the future could be done I think one of the things we have to get over first is our own reluctance to talk about research and I think as an academic institution we often don't really want to highlight that because it does make some people nervous and parents may not want that in education and the way kids learn more about that in like a high school biology class well I agree entirely it was nice to see as I came up the elevator from the parking lot this morning you got a big billboard down by the elevator that highlights research so we have to do that piece of it but I also think there's lots of creative ways using new technologies that we can engage folks that don't involve a nurse sitting down with the patient in the hospital to let me tell you about this very very difficult and I was asked away and I was mental and I was with my mother-in-law and nobody asked me about do I want to donate this tissue and I honestly have regretted it to this time I was too scared to say why isn't anybody asking me I'd like to donate the tissue nobody asked me and I was in that setting too afraid to bring it up let me collect several comments we'll bank them and then we'll get to responses a question maybe sort of bringing it down into the world we live in so you mentioned garbage so we refer to cataract surgery perhaps the cataract surgery is surgical whips and on our consent forms we actually have one little line that says you know an agreement to have a cataract surgery you will agree to having anything removed from your rod that would otherwise be discarded that you give us permission to use should we be rethinking this I mean right now we collect it and it's de-identified and we don't think of it really as a matter of specimen we think of it in surgical ways and just through this whole conversation how does it affect us or should we be thinking differently about this that's a great example let's bank that question and I think the residents kind of would be helpful to them maybe others in the audience to respond yes so Dr. Botkin I was very interested in your focus did you were you able to get a sense of the literacy level on science on scientific methods of your participant like in other words do people have an understanding that science is exploratory and sometimes in the future we really it's hard for us to say we're going to use it for this because we haven't discovered that this would be cool for that and how that might differ from like policy or what politicians might be using sound bytes and yet a lot of what it said there's still uncertainty but somehow it seems that more credibility is placed into someone who sounds confident about this I'm going to be able to stop talking about something like that as opposed to science which we tend to say well we don't know we're going to explore again we hold on to that one and it's a question about kind of their literacy and comprehension and how things are presented yeah since our residents traveled with us we've seized a lot of work to do so I wanted to to open my mind here American exceptionalism is to discuss much in international press recently national exceptionalism is something we should be acutely aware of as you know recently Pfizer was taking to task with carrying out experiments collecting specimens in Nigeria which they couldn't be what gives us you a right to do that internationally when traveling locally all residents remember the same questions which have informed concerns from some of you living in the capital all Nigeria and Ghana etc same principles should apply but you apply locally and I do take exception to this that Americans have a high standard of personal independence whereas other cultures don't I'm sorry that's not the case in international these days every culture has a very high standard of personal responsibility I like their comment about community responsibility you can't just have the latest drugs because they were developed in Nigeria and Ghana used them in England or America I think you have to this is where we must inculcate from when children are very young the principle of supporting the community at all times especially when you have minimal damage collecting a flood spot there's really no risk to you whatsoever I think we sometimes they will get and continue to create problems if we shouldn't we say I'm sorry this is unlikely to cause any harm to anybody you have to draw the line somewhere and say there's only so much permission you can ask when there is absolutely no risk I think that will generate more support and respect we'll take one more question fine let's go ahead and do that start with the question about trust and presentation and we'll go to the cataracts that are harvested what else did you learn from the focus groups yeah so a couple of things so I'll take that sort of question first I'll say we had some members of the focus group with some health care background and they had a pretty good understanding of how the system works folks without a health care background had zero understanding really have some basic issues and so part of what we did with this study was work with the genetic science learning center developed a 12 minute movie but actually talked about illustrated animated ways in which data are used and distributed and the research enterprise had a good understanding about how the system works so we've used that in a number of different circumstances and found that to be very useful for health care so folks were on the one hand surprised and concerned that these things were going on but on the other hand reassured because people's understanding of research probably is largely dominated by bubbling beakers in the basement sort of phenomenon and to understand that we take the oversight seriously was very helpful in terms of the international angle basically the regulations at least require us not to function at levels that are below US requirements in international circumstances but does also require engagement with local communities to honor their sensibilities and approach to the conduct of ethical research so decision making and consent differs in some societies with how permission is granted and so it should be designed to be sensitive to the local community in that regard but no question there's ongoing concerns about not exactly biopiracy but going elsewhere applying different standards and then utilizing that for the benefit of our society and not returning any of those benefits to the community where the research was conducted I wonder if I could start with the residents with your question do you know what the fate is of the material that is harvested from patients and what sense do you have about what information patients comprehend about the same thing so I think I know the project that Dr. Orozco is talking about and so I know what happens to it so you're talking about the capsules and we're doing gene testing on it looking for comparing patients that have pseudo-exfoliation with patients that don't I probably don't know all the details on exactly what genetic testing you're doing and where it's going for that I think the patients don't really I think we're just taking it on the informed consent that they're okay with us doing it so I don't think that they know that that's happening but am I wrong Dr. Orozco? So it's actually for the capsules we're looking at protein so it's not even genetic in Syria so let's get Jeff's comment on that too actually I wonder if I could ask a group of me, the residents know the fate of cataracts in general that is without a particular research project, arguably again because of unforeseen things you might want to retain material like that because someone has an idea that maybe later we could discover something so are they in fact treated as waste and OK so absolutely no question that other than situation there's enough of it and a lot of it coming through that it's destroyed waste So if you have an expert from the institution and I think your question is so apt it's kind of every level of concern does this constitute research what's the standard for disclosure informed consent, opt in, opt out Jeff that's a perfect question I think so my understanding is, at least with respect to pathology laws, if you are sending a sample to pathology in order for them to make some sort of ascertainment diagnosis then those do need to be retained, sounds like these are things that aren't being evaluated in that sense Yeah You know we still it's interesting because these issues come up all the time in pathology we gather specimen of patients with tumors and then we have people approach us and say we want to do a study on these tumors and what's going on with them and we want to do the studies and get specimens and it's unclear it depends on which part of the mechanism you go through you get different answers we were going to send some specimens of somebody else to do some tumor markers and we had to go through the IROV and they came up with all kinds of different things it was a six month process in order to do this where we've done another study and they said ok so long as you just get them by everything you can just send it to us directly and if it's not clear to this day how exactly we go through this particular process Yeah well hopefully we're getting a little more consistent but that's a good question you know I think if I understand how the project is going you're doing research that is basically benign with respect to and not informative for the patient's clinical status otherwise that might have future implications for that person and so the risk is low obviously the tissue acquisition is low but then the analysis or any secondary research would confer no significant risk so you know at least according to this sort of analysis I think some transparency and disclosure certainly appropriate doesn't need to be particularly robust and there probably ought to be some system in place that if folks don't like that idea they can opt out now you don't have to do that if things are being de-identified because that's still the regulations that are in place. I think just the other angle quickly that's changing some of this dialogue is the increasing set of obligations to return results to participants and I think that we as a community have not done much thinking about this until relatively recently and that's sort of the results of the research on the one hand just to contribute back to people's honor and for their contribution but then also more importantly the secondary findings and that's becoming a huge complicated debate and so if you were doing analysis on those tissues that might in fact indicate whether they're at future risk for worsening disease or prognosis or whatever then that would entail a much higher level of responsibility to let folks know that here's what we're going to do we may be calling you later here's the implications etc so it's those sort of factors that I think influence the level of engagement I think that's actually what we know and it's kind of a future oriented note and I just want to end with a paradox and I think Randy's question kind of brings it up one of the solutions to the problem of privacy has been de-identification on the other hand one of the costs of that has been the inability to feed back to people information that could be later acquired from their specimen maybe I think is a fascinating example our knowledge keeps growing and it's not inconceivable that from a blood spot in the future one might identify a condition which doesn't manifest until later in life and therefore is preventable or treatable because of new knowledge but the investigator doesn't have the way to go back to that baby that's a great thing to think about at the end and I think that's such an interesting model because it's the mom that we're asking there getting back to Jess's point about direct discussions it's a very different thing on the issue of privacy dignity etc to ask an individual who has maybe very little or even a lot of literacy and it is to ask a mom and I would venture that moms would kind of see this a little differently that is for them it might be a greater concern to give up that future benefit because of non de-identification that to participate in the social benefit that might accrue but specifically exclude their child so I think this has been a wonderful discussion your questions are great would you join me in thanking Jeff Jeff thank you thank you thank you thank you don't want to go home don't want to go home with it