 Okay, so let's move along, getting double-duty out of Jeff this round, and we're on to the next presentation in 2017, the National Academies of Science, Engineering, and Medicine assembled a committee with multiple charges, and they were to review the current practices in return of results to participants, to review the current regulatory requirements for that, that type of research to assess the available information and potential benefits and harms to patients and to participants. And Jeff actually chaired that committee, and he graciously agreed to give a summary of the report, which was published in June or July. Yes, July. And we thought it would be of interest to many people around the table. So Jeff? Great, thanks, Rudy. And a lot of this discussion, of course, traditionally in recent years, has come out of the genetics genomics community. And as I'll say in a minute, our report was not focused on genetics per se, but folks in this community have generated quite a bit of the background issues that generated an interest in this report. So here's our committee members, just an outstanding group of folks, some of whom will be familiar to folks here, Wiley Burke, for example. But people from a variety of different backgrounds, and I would say going into this report, we had no, it was a consensus report. So the task was to achieve consensus and no guarantee at the beginning that that was going to occur, given the different perspectives that this group brought to the table. So we did achieve consensus. And so it really just was a pleasure to work with this group, outstanding staff from national academies who are just very knowledgeable and hardworking. And then we have several consultants, Christy Greeny from a law perspective, Rebecca Davies supported some of our laboratory recommendations, and then Javi Morim, who's a philosopher who helped us think through some of the ethical issues. These were the sponsors of the report, CMS, FDA and the NIH. So I think fair to say, and maybe the experience of many of the folks here that return of individual research results hasn't been a standard or common practice. I've been out of the IRB world, at least not on the panel for a few years, but it was pretty typical in the past that this consent form simply said, we're not going to give you results back. In fact, a lot of times they were silent on things like whether you get your pregnancy test result back. That part's gotten better, but fair to say that this just hasn't been a strong tradition. And for good reasons, if not conclusive reasons, risks associated with return of inaccurate results. Research is by its very nature uncertain, and folks may make life decisions based on what proves subsequently to be false results, or they may be hard to understand and they may be misunderstood and, again, inappropriate decisions made. Research courses for the benefit of society and not individuals. And so there's a real concern about blurring the line between clinical research and clinical care that folks may think as with this notion of the therapeutic misconception that the reason they've been assigned to this particular group in a study is because their doctor thinks that's the right group for them. When we know the reason is to try to answer a clinically relevant question. So there's some real concerns here. In addition, prompting the report were some fairly long standing conflicts in regulations that have just not been resolved. So you have CLIA, which has been absolutely critical to help support quality laboratory services and clinical medicine. But if your laboratory is not CLIA certified, you are prohibited from returning results to individuals. And that includes under CMS's interpretation any notion that we have something of interest that we would like to confirm in a CLIA lab. That from CMS's standpoint is in and of itself returning a result and is precluded. In conflict with that is HIPAA. Again, just essential regulation over time for protecting personal health information. And the PHI includes medical records and other info included in what's called the designated record set. And we'll talk a little bit more about that. So HIPAA requires return of results requested by a participant when the entity is a HIPAA-covered entity, regardless of whether they were generated in a CLIA certified lab or not. So you've got the investigator who's on the horns of a dilemma, if you will. If a participant comes forward, request their results. And your laboratory analysis as part of your research wasn't CLIA certified, then you've got to break one of these rules. And both of them have fairly significant penalties for violation. So here is our charge. This is a brief synopsis of a fairly long set of guidelines here. But determine when, if and when it's appropriate to return individual research results to participants by looking at current practices, evidence of benefits, risks and costs, and then thinking about the ethical, social, operational and regulatory aspects. Several things were clearly outside our scope. Results not generated from human biospecimen. So our focus really was biospecimen focused research. So social behavior research, imaging research, for example, were outside our scope. Now we think our recommendations are just as relevant to those domains, or at least applicable in many circumstances of those domains, but they were not part of our conversation. Biobanking and specimens that are anonymized or de-identified were not on our plate. Aggregate results. Many investigators now are returning aggregate results, meaning what did the study show? What were the findings of the study? That's very much a laudable direction to be moving, but that was not part of our discussion. Analysis of CMS's current interpretation of CLIA was off our plate, and laboratory developed test regulations through the FDA were not part of our portfolio either. Despite that, we got a 400 page report out of it, so. All right, so a number of potential benefits for the return of individual results, and we think the key one is better relationships between investigators and participants. What I don't say here, I think I have on another slide, there's a lot of research that shows that people actually do want these results, or many people do. And you can say in the consent form we're not going to return any results, but then still as the study winds up, it's like, so okay, where are my results? How come you guys aren't talking to me about my results? So they want it and they sort of expect it as part of the relationship. And so meeting that need, we think is going to have some real advantages. So better relationships between investigators and participants, more transparency and trust about what the enterprise is about. We think then potentially better recruitment and retention, which could lead to cost savings, or maybe not cost savings, at least partially offset the cost of returning the results. And as everybody knows, recruitment and retention are a huge issue with clinical research. So anything that improves that maybe have some significant beneficial impacts. So improvements in efficiency, generalizability, participant centeredness, etc. So what are the risks and costs? Again, participants may make decisions based on inaccurate or misinterpreted information. People may well be harmed by this process. Adverse psychosocial effects, negative impacts on individuals, negative impacts on families may occur. That's been a big focus of the whole LC enterprise from pretty early on. Literature tends to show people do pretty well with adverse information. But nevertheless, has to be a concern. Legal liabilities for research institutions. So this though goes both ways. If you fail to return a result that you have that could be critically important for somebody's life and health care, maybe there's a liability claim there. At the same time, if you do return something that proves to be false, and people make a critical decision based on that information, then maybe there's some liability on that side as well. So there are legal dimensions here on both sides of the equation. No question that this is a time, personnel, resources, expertise, enterprise. This is something additional investigators are going to have to do beyond what they've done before. And that leads to potentially opportunity costs. We heard specifically from some lay advocates in the community who said, if this means you're not going to be doing more research about my baby's condition, I don't want the results. Don't spend a lot of money on that. That was one person's input. But the point being that there's opportunity costs and will we decrease the total volume of research being done by focusing some resources on this set of issues? So in general, we think the early evidence suggests benefits have been understated of return and that the risk overstated, or at least in many circumstances, the risk can be mitigated. But we don't have a lot of good data. And the costs are real, but no doubt variable. So what are the ethical considerations here? And I think our group really has some wonderful input from a variety of folks who are pretty experienced in the bioethics domain. And it's a difficult subject to tackle. But I think what we concluded was that there is an obligation to return results in a pretty narrow set of circumstance when there's sort of imminent danger to somebody that can be averted through the return of those results. And that's not a particularly common circumstance, but it's a rescue duty to war and sort of phenomenon. Another circumstance is probably not an ethical duty to return, but really comes down to an opportunity to demonstrate our respect for values that are at the core of the clinical enterprise. And that's respect for person's beneficence and justice going back to the Belmont report principles. And as mentioned, research demonstrates many participants want and expect their results. So not ethically required, but an opportunity we think to enhance respect for participants and transparency. But having said that this last bullet critical, there's certainly many circumstances where it may be inappropriate to return results for a variety of reasons. So a couple of guiding principles we identified because research results have value to many participants, return of results should be routinely considered as a matter of reciprocity, respect, transparency and trust. I'll go back to this notion of routinely considered. When assessing the value of returning results, trade offs for all the stakeholders should be considered. And that's all the stakeholders, meaning the participants, the sponsors, the investigators, the institution, etc. When results are offered, participants can decide whether to receive or share their results. This is pretty boiler plate. We're not forcing results on anybody, they get an opportunity to learn them if they want them. Communication is key to promoting understanding in the meeting and limitations of the information. Volatility and reliability will touch on quite a bit the crucial to providing value of this information to a variety of stakeholders and inclusion of diverse populations critical to the conduct of high quality research. So researchers should seek input from participants and communities to accommodate the full spectrum of needs and preferences around this particular issue, along with other issues. So decisions on return are going to vary depending on the characteristics of the research, the nature of the results and the interests of the participants. So here's sort of three different sets of issues that we want investigators to think about. One is the planned offer. One you're going to offer people the results as they're generated or at some point in the research enterprise. Secondly, how are you going to respond if you're not offering, but they're requesting? Talked about hip access, right? How do you deal with that? And then the third one that's been so prominent in the genetics domain, unanticipated findings. Something crops up that you hadn't anticipated and hopefully as folks began to think this through at the beginning, more carefully, that'll be less common than it's been with. And I think the genetic research enterprise where you had samples collected under one set of consent forms and expectations. And now it's five years later, and you've got a result that you think is clinically relevant. What are you going to do with that? So here's our general rubric. Justification for return becomes stronger as a potential value of the results to participants and the feasibility of return increase. So fairly straightforward. If it's of limited value to participants under their articulation and the feasibility is low, then there's a weak justification for return and the converse being true. Now we use the term value to participants and that's going to be clinical utility to a significant extent. But it's also this notion of personal utility. We don't want to get into that whole debate about unpacking those two kinds of concepts, you know, personal utility being I'm going to use it for my life planning, even though the doctor can't do anything with it. And clinical utility, of course, being the doctor's view of the world. So we're trying to collapse both of those into value of participant concept here. And this is central. The need for a quality management system for research laboratories, and I'm interested in feedback from a lot of members of this group. Confidence and the validity of the research results is critical. But many research labs do not have quality systems in place. So CLI is not appropriate. We don't think for everybody. I think CLI is the answer to a lot of the CLI problems is just get CLI certified. But a lot of investigators are fairly resistant to that solution. But where does that leave the community? And I think as we heard, there are research laboratories that are not CLI certified that really perform at the highest level of quality standards equivalent to exceeding CLI. But there's other mom and pop shops where folks don't pay a whole lot of attention to quality. And how does that, where does that leave us with respect to thinking about results emerging from that laboratory environment? So we think it's a worthwhile effort for government agencies to develop an externally accountable quality management system for research laboratories. Such a little bit more on that here in a minute. In addition, need to harmonize federal regulations, as mentioned, HIPAA CLIA are in conflict. We don't know how institutions are interpreting those, how they're acting based on those conflicts. In addition, FDA regulations are unclear regarding how return of results impacts the IDE process. And then regulatory conflicts create, we think, inconsistent and equitable access for participants and dilemmas for labs, investigators and institutions. So recommendations, and I'm not going to go through them in order. We have 12 recommendations. I'm going to give you a sort of a synopsis of them in different categories. So determining conditions under which individual research results will be returned. Investigators and institutions should routinely consider whether and how to return individual research results on a study-specific basis through a thoughtful decision-making process. So one of the directions we could have taken with this report was to try to say, you know, here's the types of results that are most appropriate for return. Here's the types of results that are less appropriate for return. Sort of try to create buckets of that sort as a way of guidance. We didn't we made no progress on that because of the number of variables in the conduct of research. And so it really is a matter of thinking this through on a study-specific basis. So investigators should include plans and protocols that describe whether results will be returned. And if so, when and how. Again, understanding that the decision might be we're not returning results in here, but you have to have a reason for it at least at this point. Research sponsors and funding agencies should require that applications for funding consistently address the issue. And maybe what this means for NIH applications is including another element in the application, you know, like your data sharing policy. Now you got to say something about that. Maybe you need to say, are you going to return results to participants or not? And again, if the answer is no, fine, but describe why that is. And the peer reviewers can take a look at that and make a decision about whether that looks like the right decision. Institutions and IRB should develop policies to support the review of plans to return results. And this is a new task for IRBs because they'll need additional types of expertise to be able to assess these plans as they come forward. So we really finger the National Institutes of Health here as should be the lead effort to do an interagency effort, including non-governmental stakeholders to develop an externally accountable QMS quality management system for non-CLEA certified research laboratories. And this isn't coming completely out of left field, as I understand. NCI and other institutes have done some work in this particular area. Been thinking about this issue. European colleagues are working on the whole notion of quality management systems for the research lab. So this isn't, this is a familiar concept to some extent. So here's one of the central set of considerations then. Institutions and IRBs should permit investigators to return individual research results if testing is conducted in a CLEA certified lab, okay, straightforward, or results are not intended for clinical decision making in the study protocol and testing is conducted under an externally quality management system for research labs once that thing gets developed. Or the IRB determines that potential benefits are sufficiently high, risks of harm are low, quality analysis is sufficient and information will be provided regarding the limits on test validity and interpretation. So this set of considerations below the CLEA certified lab criterion is probably most applicable to the request for information and for the incidental findings. And this sort of gets us out of the handcuffs that CLEA has provided that says if it's not CLEA certified, you don't say anything. Now we're trying to provide a path forward to say this ought to be an IRB reviewed sort of phenomenon. And many sorts of results aren't the, you know, are you going to get cancer or you're not going to get cancer sort of result, much lower valence types of considerations. And so that would be part of the formula that the review process would look to to see whether in this circumstance return is appropriate. I'm not going to go through this in detail. You'll be happy to know. But does study protocol state results will be used for clinical decision making up here at the top. If you go to yes, then CLEA certified lab is the appropriate way to go. If it's no, then we want to provide some opportunities again for the laboratory result to be generated in a CLEA certified lab. And again, this gets out of the handcuffs I mentioned a little bit earlier with CLEA where they want to say even telling somebody that we found something that we need to confirm in a CLEA certified lab environment, we need to get a new blood sample and test it in a more rigorous environment. Again, the CLEA folks say that's not permissible because that in and of itself right now is considered the return of a result of sorts. So this breaks down that problem and allows results to be obtained in a CLEA certified laboratory environment or perhaps in the environment that will be generated with this new externally accountable quality management system. On the far side here where you see the red box, will the results be generated in a laboratory using alternative quality management system processes? The answer is no, then no return of results. So we still trying to maintain quality laboratory analysis as a crucial criterion for communication. So investigators should seek information on the attitudes of the participant group being engaged for this research protocol. Now, that doesn't mean always you have to have a focus group orientation and go out and talk to people directly, although in many circumstances that will be appropriate. You got a big study like all of us that's going to be returning results. That would be entirely appropriate enterprise. In other circumstances, folks may well have adequately dealt with this community. They know community attitudes. They have people who have can speak in a knowledgeable way about community attitudes. Then you review the literature, you have an advisory board, etc. And we think research institutions should facilitate that. If you're left as an individual investigator saying, okay, what do I do to engage this community about this issue? I'm a molecular geneticist. I don't know about such things. You ought to have institutional support. A CTSA organization would be one example of institutions that are supposed to be developing these sorts of community engagement resources. So that you turn to the institutional resource to help you manage that communication. Sponsors also should engage community and participant representatives in a development of policy and guidance. So communication in the consent process, clarity is essential. Investigators should communicate in clear language to research participants, which individual research results they can access under HIPAA, and which, if any, results will be offered. So this is new, too. I'm pretty sure a lot of institutions are not routinely telling participants that they have a HIPAA access right to certain data sets, right? Because very few people access their information. Is that because they don't want it? Maybe, but maybe because they don't know they can get it if they ask for it. So routinely telling people actually then is we think is going to actually increase the number of folks who are interested in this information. If results are going to be offered, then the consent should state in brief, concise terms, clear terms, risks and benefits, when people might get urgent results, the time and process by which results will be communicated, whether results be placed in the medical record or communicated to the clinician, and when relevant to participants the option to have results here with family members that the participant becomes incapacitated or deceased. And this last one would be most relevant to certain types of research where you're dealing with participants who may well have a shorter lifespan and might die during the conduct of the research. So the time and process, I don't think I make this point otherwise, critical that we emphasize nobody's thinking that this return of results should ever threaten the integrity of the research itself. So you're not going to be returning results that might reveal which group they've been randomized to, that sort of thing. So may well be many results are going to be communicated towards the tail end of the project when those sorts of issues then become unproblematic. So effective communication strategies, investigators and institutions should communicate results in ways that explicitly convey clear takeaway messages, statements of action ability, should pair results, communications with reference information so that people can understand it. How do I, what does this number mean for me? What other people sit with this number? How do I interpret it as a notion here? Should include caveat statements about uncertainties and limitations of the results and aligned communication approaches to the different needs, resources, backgrounds of the participants. Let me just, I think the environmental research folks have really done, have been at the forefront of this over a number of years for whatever reason they've had more of a tradition of proactively returning results from environmental research studies. Folks have developed some very clever, innovative strategies to help communicate results to across communities. Sponsors and funding agencies support additional research to better understand the benefits and harms and enable the development of Beth's practices. So kind of boiler plate. We need more research in this domain to find out how best to do this and to avoid the pitfalls. Harmonized regulations to revise and harmonize relevant regulations in a way that respects the interests of participants, balances competing considerations of safety quality and the burdens to the research enterprise. This became a big topic of discussion and we think that's important. HHS should ensure that all regulations refer to research participants rather than research subjects in accordance with the ethical principles of autonomy and respect for persons. So this is kind of a seems like a small thing, but in fact it's it's very important to people. So specifically with regulations, we think the Office of Civil Rights, which is the governor of HIPAA, should define the designated record set to include only individual research results generated in a certified lab or under this new externally accountable quality management system. So the notion of the DRS is that this is information that might be used for decision making about people. And that's a big universe of data and information. But if we're specifically saying experimental results that have not been generated quality lab should never be used for any sort of decision making, then let's define that as being outside the DRS, meaning folks don't have access to it under their HIPAA access rights. Require HIPAA covered entities to conduct research on human biospecimen to develop a plan for the release of individual in the DRS to participants. Like a lot of institutions at this point just don't have a lot of experience with this because nobody commonly asks, but institutions ought to think through how they're going to do this in an efficient way. CMS, now the governors of CLIA should revise CLIA such that when there's a legal obligation on HIPAA access right to return research results, a laboratory will not be considered in violation of CLIA and need not obtain CLIA certification. Also, it should allow research results to be returned from non-CLIA certified laboratory when they're not intended for clinical decision making, etc. And this is just reinforcing the flow diagram that I showed previously. Here's a HIPAA diagram. And again, I won't take the time to go into any detail here but basically reiterates the recommendations just made about how HIPAA ought to be revised and access rights there. So a couple final thoughts. What we're looking for here is really a process-oriented approach. Again, we're not categorizing results, types of research as returnable not returnable. We want folks to think this through from early in the research protocol development process, working with sponsors to fund it if it needs to be a funded part of the activity, work with the IRB so that they're familiar and can review the protocol appropriately and make decisions in a careful manner. We think over time this is going to increase the return of individual research results as people develop the necessary expertise, infrastructure, policies and resources to do this. So important to emphasize, our committee wasn't suggesting that there would be a revolution out there, but there'd be an evolution. This is going to take a little bit of time. We want enough pressure that there's some movement in that direction, but not to suggest that tomorrow folks need to be jumping into this activity without having fully considered. So I think the initial investments will be significant, but there's going to be return on those investments in terms of, we hope, enhancing participant trust and engagement and higher quality standards for research laboratories. And of course, the emphasis with this presentation is talking about quality, allowing the return of results in certain circumstances, but probably a much bigger point is enhanced laboratory quality is going to be a huge boon to the research enterprise more generally as folks are concerned about the whole challenge of reproducibility. And so this will have quality management systems will have many advantages well beyond this issue of return of results. So there is a PDF available and I checked a couple of days ago and we had that point 4,673 downloads. So I think there's pretty significant interest in this topic. And this has been pretty briskly downloaded to this point. So I'm going to stop here. A little long, do we still have questions? Thanks, Jeff, for that report. And one of the things I'm interested in is if there are specific recommendations for return of results over time. So our understanding of the significance of specific genetic variants is going to change. And so a variant that we may have unknown may have an unknown function now may have a direct relevance to a patient care down the road. And was this specific topic addressed in these recommendations for how best to do that? Well, probably only somewhat tangentially. We recognize that problem. And it's, of course, a problem in genetics, but it's a problem in almost any experimental field where you're going to have moving understandings of what previous research had shown. We felt that the obligation of investigators and institutions specifically around the returns out probably ends with the end of the research project itself, at least from sort of a more formal structural sense of obligation. Now, it depends on the circumstance, obviously. And if you're an investigator and the clinician for a small number of folks who you've been working with around a particular health condition, then you probably have an ethical obligation to follow up with them and reinterpret. But that's not going to be the most common circumstance. And so I think that does raise some real challenges for folks who may have an understanding based on five-year-go interpretation and a whole new domain now. I've got Steve and then I'll go down. So as one of the 4673 downloaders, I have to say it's an important step forward. And the 30-plus page executive summary was also important. I would like to go back what Jonathan had brought up earlier with the polygenic risk score being so now incredibly used in not only in myocardial infarction, diabetes, and so forth. It's going to be used probably as a screening tool to say that you're at high genetic risk. You should be screened more often and so forth. The technology is such that probably the variants used in this are not clinically actionable. So how do you consider this process? Or should the academy start considering this over again? Now with respect to the polygenic risk score, where you say, what is it that we return? How do we return if requested and the entire aspect of trying to communicate this aspect of complex human disease where high genetic risk doesn't mean you're destined to get the disease, but you may want to check on your levels of biomarkers more often. Yeah. Can you do a polygenic risk score in a CLIA approved lab? Is that something CLIA labs can do? A thousand-snip polygenic risk score. Thanks very much for leading this very important topic. My question, though, is to whether or not there's a discussion in your group regarding some unintended liability issues. For example, most large institutions are self-insured and they secure their self-insurance, their reinsurance, through the assumption that they're performing clinical studies. And when there's clinical misadventure, the liability would not naturally accrue to that institution. Now, if in fact these are research results that were not secured during a clinical interaction and the research results are returned and there is a decision that was inappropriate based on that particular research results, was there discussion in your group regarding how these decisions should be communicated with risk management so that when they secure insurance, they secure insurance knowing that they're not only maybe clinical misadventures, but their potential could be research misadventures, which are usually not covered under your clinical self-insurance trusts. No, and I would say we did not develop that or analyze that set of concerns, which certainly sounds important. I think the process that we're looking for, though, is one in which at least an investigator would have substantial backup through a peer review process to say the peer reviewers thought this was acceptable. The IRB gave you approval to do this. You engage the appropriate folks to communicate the information, et cetera. So at least it wouldn't look negligent in terms of how it would be approached. And as we see the evolution of this practice evolve, then you might well say that's more consistent with the standard of care now to return these kinds of results than it would be perhaps at that point than it would be right now. So if you have an individual investigator that makes their personal decision to go ahead and do this and somebody is harmed in a current environment, it seems to me that's where liability could be substantial. I mean, I think the approach is very reasonable. I mean, I am supportive. It makes sense. I'm glad this is done. I just think that it's important that whomever takes the lead, takes this on, certainly should make certain that it is an added component of the self-insurance component because there could be research misadventures, which typically is not a part of your clinical trust. Good. Thank you. Sharon. And then, Wendy. Well, I had a separate question, but relevant to that, most of our IRB protocols actually do have language about harm. So and that you won't be compensated for harm from participating in the protocol. So the institutions must have thought about it because they're all kinds of potential harms that come from research projects, not just this potential harm. I mean, I think it's a great question, but I think there has been some look at the insurance around research harms for human subjects research. My question is, is I'm one of those researchers in the middle. And I think the report is excellent, but what's the plan for the interim? There are thousands of patients who have or some participants who have given samples for often very serious illnesses where the lab won't have fallen under this new structure. And I haven't read the report yet, but is there some discussion of the interim? Because there are definitely people in my own genetic studies who have Hipporites and had language about returns of results that won't have met this new standard, which I think is a great idea. Yeah. And I would say no, we'd have not dealt with the complexities of the interim in which, you know, as mentioned, the old consent form says one thing, the new science is proposing new dilemmas. I will say, though, that Barbara Bierer's group has come out with a nice statement. And I can email reference to you. I can't remember the name of the group that she worked with to do that. But basically, to some extent, it was also a process-based organization by setting up what they called some institutional informed consent support groups or something. But basically, it was a notion of experts who can help advise institutions and IRBs on how to deal with incidental circumstances or unanticipated findings as they come up now, specifically with this conflict. I would argue that it's not always incidental. In fact, the results I've returned over the last 15 years have more been actually finding the cause of a disorder where the child has now died. And there's no possibility of having a clear sample, but for which it's highly relevant for the rest of the family. So I don't think these are all. I think incidental findings are important, but I don't think we should ignore that most people and our research studies because they have an interest in a particular disease in the family. Yeah. Well, I'd refer you to that Barbara Beers work on that that might give some additional guidance on the awkward period we're in. Wendy. It seems to me to be able to scale this, especially for folks that are non-geneticists. There are three components that could centrally be built to enable this. Part of it is data generation. Another segment is data interpretation. And then the third is actually a mechanism to return the information in a responsible way. Did the committee think about that or foresee that that's the way the community would go? Or is this going to be each study sort of out for themselves in all three components? No, I think we've thought quite a bit about the kinds of expertise that are going to be necessary here. And particularly those elements that were somewhat new to the landscape. And I would say the laboratorians and understanding laboratory science and laboratory standards is not something IRBs for the most part have familiarity with. So they're going to either bring in experts or seat somebody on the panels with that level of expertise. In addition, very impressed with our communication scholars who could help us understand better ways, standard ways to communicate stuff. And I think a lot of us in medicine and sciences think we're communicating effectively. But there's lots of research and principles out there that we very much benefit from. And a lot of times those folks are at our very same universities, but we've never talked to them, right? So that's sort of this notion of bringing other folks in and potentially doing that very much on a research basis as we get into this. So instead of just returning results, why not return results under an experimental protocol so that you're actually collecting data on that piece too while you proceed forward. So I think we did recognize that there's new faces at the table with this. Nancy? So just a final comment on the polygenic risk scores. They've really flown under the radar in all of this stuff. And it's a little bit crazy that it's not being addressed at all in any context in terms of do you know, clear? And it's not even, I mean, people have to be aware it's not just in return of results. It's actually in the use of the information in this hole under the radar space of, you know, all of the modeling that learning health systems already do, the prospect of just adding genetics to that, is there going to be any, I mean, is there regulation needed or not? And, you know, are people just going to start doing it in the absence of any further discussion? It's a little bit of the wild west out there with respect to this. And I think because so much of the LC space has been in large effect variance and the people who've been working on this, it really has flown under the radar very quickly. And it seems like somebody needs to draw attention to this space sooner rather than later. Well, and I've been very impressed just with the discussion over the last hour about this particular issue. And I guess I would make just a couple of comments in this context. It seems to me that I don't know what with the various findings that are being published now, what would one consider to be the clinical validity of those findings at this? But what's the analytic ability to begin with? I don't know. What's the clinical validity? And when is it right for return? It seems to me I would be reluctant to have individual IRBs and investigators try to make calls on some of those things at this point. And this seems to me pretty right for professional societies to sort of pick this up and say, here's the state of the art here. We think this is the best thing since sequencing. And everybody ought to be doing it or whatever the professional opinion is to give guidance to the whole community about this emerge. Domino. Any time. What is the policy? So enough has been said about that to highlight the idea that it's there, it's coming. And whether it's validity and it's clinical applicability is still there, but there it is. The other thought that I had as I was listening to you and that echoes a little bit what Wendy said is that we're returning results now in part of a large emerge project to participants. Use the right word. And one of the things they do as part of that protocol is go off and discuss the results with their primary care physicians. And the group that is giving us the biggest pushback right now is the primary care physicians. I didn't ask for this. I didn't want to do with it. And yet they are a critical part of how people will handle that information and their health care going forward. So some mechanism to engage in. We've said this at this meeting and many other places over and over again. But some it becomes more and more urgent as you start to return results to patients. And they have this expectation that somebody is going to help them. Somebody beyond a website is going to help them understand what to do for themselves and their families. It can't all be genetic specialist because there just aren't enough in the world. Jay. So I mean, just if you look at that graph of the number of people who've had genotyping done primarily for ancestry reasons, it's like somewhere between 10 and 20 million and going up at a very fast rate. And so at some point in the next year or so, someone is going to put up a website where anyone can go and plug in their results, which will primarily really not be obtained through the medical system, but rather through these ancestry or whatever it is, and get some prediction. And there's a little bit out of scope of return of results, but it's going to happen inevitably create headaches. And I'm just curious. I mean, I don't know if anyone's really thinking about this yet. I'm sure people are thinking about it, but it does seem like an area which merits some regulation or at least some close attention. So interviewed in The New York Times after his article came out, Sake said he's putting up that website. There you go. Please say it right now. And I trust him to do a good job of it, but I'm sure other people will put similar websites up. And yeah. All right, thank you very much, Jeff. Thank you. I'm so anticipated it was of interest to this group. So let's adjourn for lunch. Can we be back at one 15 in this room? And again, for the council members, we're bringing the food into you. See you at one 15. So you guys are on lunch right now.