 I'm Tos Cochran, I am the Director of Neuroethics at the Center for Bioethics, and I'm glad to welcome you all here for the first time, or if not, welcome back from the summer. I hope you all had a lovely summer. I'm very excited about the topic for tonight's Neuroethics Seminar. There's a great way to kick off the fall series. We've got a number of topics this fall. The next is called At the Frontier, the Ethics of Innovative Neurosurgery, but before I dive into the topic and introduce our speakers and commentators, let me just sort of give you a flavor of what's to come for the rest of the fall. On Tuesday, September 29th, we have a seminar on the Ethics of Disordered Consciousness and the implications of neuroimaging in disorders of consciousness. On Wednesday, October 21st, the topic is DIY Brain Stimulation, and we have our guest speaker is Julian Saviolescu from Oxford. On Thursday, November 5th, we'll be talking about the Ethics of Presumed Consent to IVTPA in Acute Stroke. And then December 3rd, we're going to be talking about Brain-Computer Interfaces. So we've got an exciting lineup, and hopefully you can return if you're able. I want to acknowledge the entities that make this possible through their financial support, and those are the Mind-Brain Behavior Interfaculty Initiative here at Harvard, and the Harvard Brain Initiative Collaborative Seed Grant Program. We're also supported by the International Neuroethics Society, which supports our ability to webcast these seminars. So in a moment, I'm going to describe the case that we're going to be used to focus our remarks about innovative neurosurgery, but first, let me introduce our commentators tonight. Paul Ford is our visiting professor. He is the director of the Neuroethics program and the education director for the Department of Bioethics at the Cleveland Clinic, and is associate professor in the medical school at Case Western. He has a PhD in philosophy and is a professional ethicist. He's an extremely experienced ethics consultant. In his primary research interest center on ethical issues raised by neurosurgical interventions, which makes him a perfect commentator for us. He also brings us the case that we're going to be using. For more than 10 years, he's been part of a deep brain stimulator team and the epilepsy surgery program, providing ethical advice in clinical cases and on research. Our second commentator is Dr. Darren Doherty, who is an associate professor of psychiatry here at Harvard and at Massachusetts General Hospital. He's the director of the Neurotherapeutics division in the Department of Psychiatry at MGH, and the associate director of the MGH Psychiatric Neuroimaging Group. He co-directs the Harvard Catalyst Masters program in clinical and translational investigation, and co-chairs the MGH Psychiatric Neurosurgery Committee, and as you'll see, that makes him likewise a perfect commentator for tonight's session. And last but not least is Elizabeth Homan. Libby is an associate professor of medicine and an expert in infectious disease at MGH. She's an experienced researcher in her own right, but more importantly, for our purposes tonight, she is the chair and physician director of the Partners Human Research Committees, the IRBs at Partners Hospitals, which is a big job, and you've held it for many years. So very experienced in the regulatory aspects of innovative neurosurgery and other research. So with that said, I'm going to introduce the case for tonight and then let our speakers take it from there. Our case has to do with consideration of deep brain stimulation for an adolescent with Tourette's syndrome. A little background on Tourette's syndrome, it is a spontaneous disorder characterized by motor and phonics ticks with an onset in childhood. The severity often peaks in early adolescents, although about a third will improve as they become adults. Some patients are disabled with respect to daily functioning, partly because of the social aspects of their ticks. They can be quite visible and audible and can interrupt social functioning. Some of them are actually painful and can interrupt physical function. So it can be a very, very severe disorder. There's a high rate of mental health comorbidities associated with disease. In particular, obsessive compulsive disorder has a high prevalence among patients with Tourette's syndrome, but depression and attention deficit disorders are also common in that population. Deep brain stimulation, which Paul will introduce to us a little bit more shortly, is a technique that has been used in Tourette's syndrome, although not in a very large cohort of patients. About 120 patients have received DBS. Only nine of them were under 18. And it is the experience of people doing this, is that there is symptom improvement, but the evidence is still class three. And so we don't have any scientific proof in scare quotes that it improves symptoms. There is no standard brain location for the insertion of the DBS leads, the basal ganglia is the most common location of stimulation. And then there are thalamic targets as well. The case for tonight is a, what is it right to say, it's a slightly fictionalized case that Dr. Ford brings to us. Patient we'll call Mike is 15 and was diagnosed with Tourette's syndrome at age 10. He has motor and phonic ticks that include severe head snapping ticks, so head movements that can be very disruptive. And they can actually be dangerous if they're severe enough. They can actually cause trauma to the neck. And in severe cases, they can cause dissection of arteries in the neck. A panel of experts in movement disorders viewed video of his symptoms and agreed that his ticks were related to Tourette's syndrome. But it seemed to them that some of his head snapping behavior was likely embellished and included a psychogenic component. His ticks have worsened to a level that he is now homeschooled, which is something that he and his family and the school district agreed was necessary. So it gives you a flavor of the severity of his ticks. His family is worried about his social and emotional development quite naturally, as well as the potential health consequences of the ticks. He's tried all of the major classes of medical therapies without sufficient relief. The family, it's been suggested that he undergo cognitive behavioral therapy, which is a standard part of the therapy for Tourette's syndrome. But the family doesn't believe in psychological therapies and has rejected the idea of CBT. Mike saw a news story that reported deep brain stimulation as, again, in scare quotes, curing a man of his Tourette's. He's under the impression that this is a miracle technology and he just wants to have a normal life. And he is constantly asking his parents if he can receive the surgery. The medical center in our hypothetical discussion tonight, it has an active deep brain stimulation program. But no current active research protocol for DBS in Tourette's syndrome. The parents have reluctantly brought Mike to be evaluated for DBS. There are any number of ethical questions that we could ask at this point. And I'm not going to try and set that up. I'm going to leave that job to Paul Ford. And unless there are any fact questions about the case, I will sit down and leave it to Paul. I'm sorry, there's a last little bit of detail. The Tourette's syndrome specialist who evaluated him thinks that his ticks are unlikely to remit. But there's no scientific method for knowing whose ticks will remit. And there also aren't any studies that tell us what the long-term implications of DBS in young patients with Tourette's syndrome are. There is some experience in children who receive DBS for dystonia. I wasn't sure if you were gonna, but if you could tell us a little bit more about the device and the- Paul's gonna tell us a bit about that and that's you. So I'll tell, I'll say a bit about the device. And Dr. Doherty will be able to fill in the details that I can for more sophistication. Probably, thank you. So thank you, Toss. And thanks to the program for inviting me. It's a delight to be here. I had an opportunity to visit Mass General a number of years ago and sit in on the psychiatric, neuropsychiatric surgery committee which is the longest standing program, multidisciplinary program for these kind of neuropsychiatric surgeries and done very well. So it was a delight to come and participate with this group. Now I want to say a minute more about thank yous. I think it's good to be appreciative of where you've come from. You know, there's a lot of people who have helped educate me about being a philosopher in neurosurgery, neuropsychological, psychiatric illnesses, challenges, the decisions that arise from these. I'm also humbled by the opportunity to help clinicians, families, patients make some of these tough decisions. And so, you know, most of all I put patients and families first because they trust often to disclose things and allow me to help with some of the decisions. So the case we have today is one that is published in literature and then I added in elements from the various families that I've met with. So all the elements are true. It just wasn't a single patient. And although sometimes we meet patients that have all these complexities all in one. And certainly the clinicians, too many to list, but pediatric psychiatrists like Tatiana Falcone, adult psychiatrist Dr. Jimenez, Malone, Pandia, neurosurgeons like Dr. Machado, neuropsychologists like Dr. Kaboo, neurologists, these all collaborate and help me understand. So I want to frame this and give a framing for the discussion today of justifications. So when I think of ethics, I think of scenarios, dilemmas where we're forced to balance values in an appropriate way. What values are we going to preserve? Which values are we going to give up as important to our patients? So the three framings that I'll use as a theme for this, we want to ask ourselves what is the justification for offering a surgery to this child and family? If we offer it, what's the justification for which framework that we're going to use in order to say how we're going to perform it? And then finally, and this may be a little bit different than usual, the justification for putting special conditions or requirements on the patient in order to get the surgery. That's probably the most unusual of these three. So just a very thumbnail layman's understanding of deep brain stimulation. So people often talk about it as a pacemaker for the brain. And in fact, one of the largest manufacturers took a heart pacemaker, modified it, refined it. There's a generator that gets implanted in your chest. It's hooked to wires that there's burr holes usually on two sides, sometimes unilateral, but often bilateral. And then electrodes are placed deep in the brain usually around the basal ganglia. And then there's for at least the standard indications, high frequency continuous stimulation into the brain. Indications include a central tremor, Parkinson's, human device exemptions for dystonia and OCD. And then there's lots of experimental experiments. But those are the main, the biggest experience, 100,000, almost 200,000 DBS leads implanted worldwide. Okay, so I'm going to frame even more and frame what the salient features I want to pull out of the case that I thought are particularly important. It's deep brain stimulation for Tourette's, an approved device, but not approved for this indication. We really have limited availability of data available. Shrek had us writing for a big collaborative in movement disorders. Just this spring had this wonderful review of all of the published cases. And again, in your case write up, those are number of published instances. We don't know how many people are actually doing this off-label, but at least they found those numbers as a minimum. This is a 15-year-old with a developing brain. The other interesting thing about the Shrek et al. article is that they reversed their stance on whether kids should be eligible potentially for DBS for Tourette's. The previous iteration of this group was it shouldn't be done under 25. They moved that to say with special consideration and special oversight, it is permissible. This is in a little bit of contrast to the 1977 psychosurgery and that's the term they used in 1977, report that sort of suggested that children ought not to be and if they are you needed at least a court finding that they'd be eligible for. And we have this interesting developmental window. So people say why not wait? Well, we have this developmental window that we're shaped deeply in our adolescent years the rest of our lives. Opportunity to educate, opportunity to socialize, developing the developing brain and opportunity. This idea of managing expectations on media, magical thinking, the team's expectations. And then this twist I threw in about potentially some of these are psychogenic, psychological, functional movements that might not be helped with a surgery and the family for whatever beliefs, core beliefs, religious or otherwise is rejecting cognitive behavioral therapy. The very therapy that's most likely to help with a psychogenic component. So we have some contrasting values at stake here. So again, justifications. I'm going to start with the very quickly with the justifying offering surgery and then I'll go through the other three. But I want you to ask yourself what's at stake in making these decisions of which framework, which offering, which requirements? Who has something at stake and what are the values either lost or preserved? So justifying the even offering. So oftentimes committees like the one here at Harvard, they meet and the first stage is even whether it's ethically justifiable within their conscience even to offer the surgery to this child and the family. And we use some of the usual kinds of things. Is there a reasonable chance of benefit? Well, is a developmental benefit enough justification when it's not a life-threatening condition? In the case it was given, there could be an avoidance of physical harm if he's snapping his neck. Is it only going to be for those who have physical harm that we're going to offer this to? Or is this developmental enough? Does the dystonia experience or the adult threat experience really translate to the kids? My pediatric colleagues make sure that I know that kids aren't little adults. They're different, particularly their brains developing in different ways. Do we know the uncertainties involved of a lifelong of deep brain stimulation in this kind of brain? And are you going to exacerbate those other potential underlying psychological illnesses? Or are you going to unmask more? And then we can look at this not just for this type of patient, now this kid's specific circumstances. And then I want to say that every center should ask themselves is this the right center to do this? If our focus is a lot of other things, maybe there's a center a thousand miles away that specializes in this. And we have to have the humility sometimes to say the higher volume center might be a better fit for this indication. So once you decide, yeah, okay, we're going to offer it and let's say our team thinks it's justified to offer it to this family, this patient. The next step I think is to say where along the innovation and research continuum does it fall? Under what conditions? Am I going to offer it simply as an off-label use just for this person's benefit and every decision will be based just on what I think is going to maximize the benefit of this kid? And I list up on the screen what I see as various versions of this. And a continuum. It's not binary. It's not either research or maybe you do it and then you submit there's a big registry, data registry, national data registry, international data registry now that they've created for Tourette's. Maybe you submit and then you send all the information to this registry and that part is research. Or maybe you add a few extra tests or how much extra do you do to say, okay, if we're going to do it in one we need to learn and benefit others. Right down to the full should this only be done in a rigorous controlled randomized sham or placebo controlled trial? That decision then will carry through all of the rest of the decisions you make. In terms of the framework it says what kind of consent process. If you're going to do a full controlled trial with a sham you may require a greater level of consent. And that's where you do actually involve a court appointed person. I doubt that that's really needed in most places. But this will change. Particularly in an adolescent that this is a quality of life surgery. You're going to put their life at some risk small but any neurosurgery has its risk. Is this justified and what consent would we need? And then what evaluation process? Actually how many hoops do you have the patient come through? You know I want to say just a minute about vulnerability. It's easy to say well this child is vulnerable. And you know this was a definition that I like put together. I think vulnerability is when you run into a circumstance where the usual safeguards for fair and just action aren't usually sufficient enough. So vulnerability should be just a signal to say the usual circumstances aren't going to protect fairness and justice the right way. So do we need to not do it or maybe just put in new safeguards. And vulnerability I think is negatively associated with both voluntariness and appreciation of implications for consent. And I also want to stop people from using vulnerability as a catch all term that's a conversation stopper. You know here is six ways. Kipnis and a couple of nice articles, I list them as seven. I reduced it to six. But I want to if I have a discussion with a surgeon I stop and say vulnerable do you mean he's under the control of his parents? Vulnerable in that this fancy institution of Cleveland Clinic or Harvard is not letting them make good decisions. Is it that they have no option? Which of these vulnerabilities do we need to protect against? Not just one big grouping. Okay, my final justify. So we've decided that we're going to offer it. We've decided whether it's going to be research or clinical practice and what kind of innovation, what we're along the spectrum. And then there's this odd dance I think that we don't often recognize between how we were able to put conditions or requirements on the patient. The conditional is you will get surgery if, if what. And do patients and families have obligations in this kind of innovative neurosurgery? Where you're very expensive to do a surgery, lots of resources, high risk potentially to the institution in many ways. Does that put obligations on patients and families? And what do obligations mean in this context? So what justifies conditions being placed on the patient? You might think some of these might be ones that you'll, you'll trot out. Standards of practice. It's standard of practice to have everyone have a neuropsychiatric evaluation, hence it's a duty protected as a physician, it's your duty to protect. I have a responsibility to protect the reputation of my program and colleagues so I can continue to help other patients or outcomes reimbursements attached to outcomes these days. Maybe I have a duty to responsibility to have good outcomes. Maybe I have a responsibility to avoid futile or wasteful interventions. Maybe I want to say that the patient in fact has obligations to others or obligations to others with a similar disorder. You know, I had an interesting conversation with Zeke Emanuel one time where he, you know, outright rejected that one criterion pediatric research if it's a benefit to other people with the same disease. Does that hold water? Do any of these justifications hold water and for what kinds of conditions? I'm trying to set this up for a conversation that we can draw on these. So what kind of conditions, conditionals might we have? The first one and most prominent is you have to fail all other therapies first before we'll offer this innovation. And you already see with the way I wrote this case up. I tried to call that in the question. Is it because this is the last resort therapy that's unlikely to help and so we're going to need to be sure that everything else has been exhausted. Is it that you have to demonstrate less risky attempts and you notice I didn't put less invasive. You know, I want to reject less invasive as a good criteria. I think it's less risky because there's lots of things we think of as noninvasive that have pretty significant side effects. I saw a person with the same Natasha Tardive dyskinesia after antipsychotic and it was so horrible that she was breaking teeth, right? It's not invasive, but you know. So the metric I want to use is demonstrate less risky have failed or is it that you want to demonstrate that all proven therapies have failed and you're not keeping them away from a proven therapy or you're really demonstrating compliance. If we're going to give you the opportunity to have this expensive, innovative thing, we want you to earn the right. Now nobody is going to say that outright. I'm trying to get at what's perhaps some of our underneath assumptions we may not recognize. So what kind of conditionals? Agreed additional things, safeguards, after care, before care. There's been some discussion about a parent having to sign over all of their decision-making, parental decision-making because they were non-compliant with their kid. Is that a condition that the kind of condition that's justified? You have to get these unrelated health benefits that will be beneficial for you and I'll hold this surgery over the head until you do. And finally, most interestingly, agree to be a research subject. And I think this is often missed in the conversation that we say, we jump right to, well, we have to do this under research. So research affords perhaps some extra protections but it also creates an extra burden in most cases. Extra tests, you have to share your data, your personal information. So research has a burden to it that are we really justified in saying, the only way I'm going to give this to you is if we create a little research protocol. I'm going to save this for discussion but simply I think that outcome measures are pretty important if we're going to study these things and maybe we need to think about neuropsychiatric indications as a grouping of domains and symptoms and we could be satisfied with just helping at least one symptom rather than the ham D having to be improved all for depression. Maybe it's there's some subscales that would be sufficient just like in tremor, tremor for Parkinson's and maybe the severe neuropsychiatric illnesses need a multimodal approach. I think of the analog of cancer. Many times it's radiation and chemotherapy or surgery, radiation and adjuvant chemotherapy. So I push back on one famous neurosurgeon when he wanted to talk of DBS as a cure for OCD without any further therapy. He may be right, what do I know but I suspect there are some people who DBS in conjunction with psychiatric therapy might beneficial. So maybe we need to think of this not as one but as a treatment program and then you ask yourself can you order off the menu or is it a package deal? Okay, we need to think about are we justified in offering the surgery are we justified in which framework and when we choose a framework are these conditions we're going to place on the patient and the patient's families are they justified and reasonable? So thank you. So Darren I think that tees us up nicely for what you've got to say. As I mentioned you're part of a group actually doing these a term that some folks don't like psychosurgery. Psychiatric neurosurgery. Psychiatric neurosurgery at MGH and I think your insights about this case and Paul's remarks would be welcome. All right, great. So the psychiatric neurosurgery committee at MGH has been in place since the 1960s believe it or not and I've been part of the committee since 2000 so for 15 years and currently serve as co-chair with the Mod Eskandar neurosurgery and we meet once a month and we review cases they have to be referred by a physician patients cannot refer themselves they provide all of the records that we need in order to evaluate the case and usually at the meeting we'll sometimes outright reject we'll rarely approve at the first meeting usually we would end up happening to something in the middle where we either ask for clarification on issues or we have additional recommended treatments before we would proceed with surgery. If they go through all of that then we will invite them for an on-site evaluation that if it goes well we'll end with a surgical procedure and the committee itself includes neurosurgeons neurologists and psychiatrists and all three of those groups see the patient when they come on site as well and we reserve the right that if we detect anything during the on-site visit that makes them ineligible to revoke their candidacy we also do lab tests neuropsychological testing, brain imaging, etc the majority of our cases are for two indications and we have two different procedures that we use the major indications for the psychiatric neurosurgery committee are major depression and OCD we've done a blade of limbic system procedure since the 1960s which is stereotactic ablation of small areas of the brain that we know that are effective for both OCD and depression we've published extensively on that and that procedure is called an anterior singulotomy and we ablate a small couple of cc's bilaterally dorsal anterior singulate tissue and that's effective and for many years that's really what we did with the advent of deep brain stimulation now over the last decade that's been added to the mix and we've been involved in doing some of the OCD cases that led to FDA approval for intractable OCD by the FDA under humanitarian device exemption which is kind of the device equivalent of an orphan drug approval and we've also done open-label trials at targets for major depression those looked promising depression because of its higher prevalence could not be approved under an HDE orphan it needed a full pivotal trial in order to go forward and so we just recently published the results of that trial and it was negative so it was not effective for major depression and I guess bringing it back to this case so that's kind of the framework that we work in and hopefully I've done it for 15 years and it's been around for 50 plus years this committee and Paul's joined us before at our meetings for this particular case I would say our experience we've done in the time that I've been on the committee we have done surgery for Tourette syndrome in two cases the one I remember most vividly because it's the most recent but also the most graphic was a postdoc researcher within the partner system that had such severe movements ticks over her heads that she was detaching her retina and the ophthalmologist were going in and reattaching it but it kept detaching and they said we're not going to keep reattaching this unless we can somehow get the Tourette syndrome under control now she had tried pretty much all medication trials that are known to have any efficacy for Tourette's and had done the cognitive behavioral therapy but it was really life changing for her she's still ticks but it's much more gentle no risk not nearly violently enough to detach her retina they've both been reattached and have remained reattached attached for the last five years so we saved her sight essentially but we've never done an adolescent so I guess that's the gist of this now we have done the anterior singleotomy in patients as young as 16 so we do have that experience we've done two kids one of the difficulties with kids and adolescents is usually the time it takes from onset of illness to correct diagnosis to going through each of the treatments each one can take months and then the behavioral therapy usually by the time they meet treatment criteria they're not a kid anymore so that happens so that's probably why we don't see it a lot of course if you were to lower your threshold as to what you required in order to proceed with surgery then it would not take as long and that's happened in the epilepsy field the resections and the like were all the adults and then they realized kind of comparable to this case for this epilepsy these people are in their developmental trajectory and what we're doing is we're waiting for that all to finish and then we intervene what would be the implications if we were able to intervene earlier and change that trajectory for the better and so epilepsy surgery has moved into the pediatric realm and then as Paul said in dystonia dystonia these people can get stuck in a certain position like this for example that they can't get out of and you can imagine a 14-year, 15-year old kid who's tried all the medications and the like you wait until they're 18 years old or do you leave them stuck in this position unable to move any other way for three to five years so I'm happy to answer any questions about our psychiatric neurosurgery committee and how we've done but that's kind of a framework on how at MGH we would handle this case it would come to the psychiatric neurosurgery committee and we would address it in that format trying to figure out how to turn this on but I can yell too you've got a good voice Libby I have teenagers at home I'll make it work all right one of my questions for you is how many cases do you do a year we do two to six ablated procedures and two to six DBS cases per year so we probably average one every one to three months and we're a high volume tertiary care center our referrals are from all over the United States in the world so it's not like this is a high volume business very good point so but your DBS program for non psychiatric indication is a high volume very high volume I believe Ahmad himself are the neurosurgeon that I've worked with for 15 years he's done five to 700 cases himself so very much higher volume I just want to give a context that this isn't a place that does a couple of these surgeries a year they know this technique are expert in the world for this indication it's very selective yeah that's an important point because it's the same device that's used and has been implanted in over 100,000 people for Parkinson's disease for example I think they passed that milestone a couple of years ago so it's even higher now it's the same device the only difference is the target is to where the electrode is placed for these alternate indications so where do you put it in Tourette and how did you figure out in that case you mentioned well the good news for us is we weren't the first and there were two targets where there is literature that suggests it can be helpful for Tourette's and interestingly on the two cases we tried one target for one patient and one target for the other and found them both to be helpful anecdotally but the two targets are the Globus pallidus interna so that's in the basal ganglia it's also a common target for Parkinson's disease usually use the GPI or the subthalamic nucleus STN for Parkinson's the target is the central nucleus of the thalamus there's a lot of evidence in a lot of cases have been done at that target for Tourette's as well and so we've done a case at one case each of those two targets do you have any focused ultrasound on the way that's another technology so I'll say two things one thing before I answer that also just remembering what Paul had on the slides we did these cases as pure clinical cases we didn't feel right given that there were kind of one-offs like humanitarian exemptions for us going out of our standard diagnoses that we should have any type of research the benefit should all be for the patient and so we did not add any research burden to either of those two cases and then your question was the focus ultrasound there's new technology now where it's already been developed in the gamma knife neurosurgery for example where you have thousands of gamma rays going through the brain and any one of them the energy level is low enough it doesn't affect the brain tissue but stereotactically you can within a millimeter or two define where the intersection of those gamma rays occur and at that intersection the energy level is high enough that you can ablate brain tissue without having to do the burr holes in craniotomy a new technology is the low field ultrasound ultrasound is already used in a comparable manner about a lithotripsy for renal stones but now stereotactically you can also use these ultrasound rays to do the same things with gamma that you can with the gamma knife the advantage of the ultrasound is the lesion is immediate and it doesn't require radiation what happens with the gamma knife is there's a high dose of radiation delivered at the intersect and the lesion doesn't develop immediately it takes some months to develop and if you look at the literature occasionally it will over develop and they'll develop cyst so you'll have a lesion larger than you wanted to and low field ultrasound looks like a way for us to achieve what we do with the gamma knife without the radiation and overly enlarged lesions happening so we're on the way to getting that technology as well so can I follow up with one question the you did the two cases for clinical purposes didn't change anything to collect extra data right but do you think given that there are 1's and 2's and 3's across the country now that there is a Tourette syndrome DBS database being is there a positive obligation for you to contribute to that yes and does that require you to go back and get consent from the patients or do you think that that should be is that a a special thing for the patients to do or do you think that's sort of their duty because they benefited from a therapy like this I think it's our duty to ask them and for them to consider it but we would never if they were ever against us publishing or including their data in a database we wouldn't do that so in both of these cases that's exactly what happened Paul is after we saw that they had improved we got their consent to write them up and we published them both as case reports and then we the Tourette syndrome association of America the TSA maintains and curates the Tourette syndrome DBS registry which just gets all of the cases what the target was what type of changes on the scales we used to monitor Tourette symptoms and we added both of these patients again with their consent to the Tourette to the TSA registry I think this becomes interesting if you now in your next case if you know what the data fields are for the registry I imagine there's a temptation to say this could contribute even more if we just collected make sure we collected the fields that we otherwise may not have collected and maybe it's good practice maybe it's extra but is there that incentive or temptation there is fortunately most of what the fields that are populated in the TSA registry a lot of it is demographic a lot of it is the target and then where it gets tricky is the outcome measures and so what we argue and we can talk a little bit about this is there's a TS scale that measures the severity of ticks and a quantitative measure and it's used clinically what we're doing with medication or with the specific type of CBT habit reversal therapy that's used for Tourette's and so we justify using it because it's used for those things but conveniently it does fit nicely into the registry so there's a fine line there we do think we're justified but it would be the case would almost be useless to the registry without that outcome data so there's no doubt about that and I think well positioned to let Libby talk to us about the regulatory environment for this sort of thing and Libby there's any number of angles on this but I think we love to hear a little bit about when innovative surgery has to be done under the auspices of research when an off-label indication really crosses the line into something that needs to have a new investigative device protocol that is associated with what the consent process might look like especially for an innovative surgery that's only been done once or twice or a few times and what implications arise when the subject is an adolescent so lots to handle and if you've got other topics you want to tackle those are good too wow first I'll say either of you guys can join my IRB anytime love to have you these are really challenging areas and difficult to understand from a regulatory perspective I think it's very challenging and I'm not sure if everybody is familiar with the HUDs, Humanitarian Use Devices or HDEs Humanitarian Device Exemptions which is a relatively new thing at the FDA probably since about 2000 or so where devices which are not anticipated to be used in more than 4,000, that's a pretty big number 4,000 people in the United States can go through this other pathway to approval and essentially what it requires is the company to generate some basic effectiveness and safety data in a small number of people and the neuro psychiatric devices are one example of this the dystonia approval that was mentioned another approval is just a few things so you get the flavor of these a valve that's implanted in a one-way valve for people who keep having recurrent pneumothoracies sort of really weird sort of things that don't happen very often a device used under these needs to come through the IRB they can't be used at the institution until there is IRB review and it has to be full panel review we used to be able to do this with the clinical care sort of but they've changed that so it has to go full panel and then we get into the issue of whether you can use HDE devices off label for care not as labeled and you can see how we get into these very complicated sort of decision trees and thought processes you know we at the IRB do not regulate the practice of medicine so there are certain things you can do with appropriate mechanisms and oversight and decision making groups at centers and Darren's group is sort of like that another group that functions in that way are some of the committees that oversee challenging transplants at our institution so you don't get a kidney transplant until you know that multidisciplinary kidney group looks at all of these different aspects of your case which include some fairly squishy things like your psychosocial situation and are you going to be able to afford and take your immunosuppressive drugs so these are really challenging areas and I think it is incumbent upon us to have to do some of this work under clinical auspices but have a very formalized way of deciding who gets this and who's appropriate and it is a multidisciplinary thing and one of the questions I wanted to ask Darren was and I think I know the answer to this or all you do is what input does the kind of insurance you have or the ability to pay for these things play in these decisions and I'm familiar with cases at both of the institutions where the physicians the surgeons, the staff and sometimes the companies will chip in and do some of these things and people who are so severely affected and it appears that this is the best course of care in the situation where the person doesn't have a nickel and doesn't have insurance and those are really challenging areas and probably the topic of a whole other discussion in terms of deciding when to do something as care versus move into a formal clinical study I think that's a really tough thing to make and a tough decision to make and we have to think carefully about that and then you have to think about the design of the study which is some of the things you were mentioning how much does it add, how much burden how much sham, how much everything and how do we decide to do that and that's really challenging and something we we occasionally see although I have to say I think the majority of this work is currently proceeding as care we do and Children's Hospital has another mechanism for oversight that we call innovative diagnostics and therapeutics and we've had this on our books for a long time and essentially what it does is allows a physician investigator to come to us with something that they believe is primarily directed at the care of the individual but they'd also like to do some research component to it and sometimes it can be even a fairly significant research component in terms of blood sampling, scales mandated follow up and so forth and that is a mechanism that we've used and Children's has also kind of glommed on to for want of a better word to provide some additional oversight of challenging cases that span this bridge between something that's done exclusively for clinical care and something that's research in our policy we have a very strict limit of three is the maximum number of these that you can do we have a way that they're reviewed it requires multiple physicians agreeing that it's an appropriate approach for the patient we think about how consent is obtained and so on so that is one way to look at these challenging situations I would caution that you need to be pretty careful to be sure you're staying on the right side of the FDA regs in not sort of doing de facto device research requiring an IDE and I will also maybe one of my final comments after I talk a little bit about the consent I will say that the FDA has been clear in my dealings with it that they want the IRB to make their best decision about whether they need to interact with them or not so we get first crack at it if we don't know we can refer it to the FDA for their opinion and then the investigator or physician is obligated to go to the FDA I will say we've made a lot of these decisions I think most of the time we make them right there's a couple situations where we've made them wrong where we at the IRB said no we don't think an IDE is needed there we think you can go ahead this is close enough to the label we think this is good enough and I'll just give you an example of this I'm not sure if you're familiar with the power more salation thing where you put a stick blender into somebody's abdomen and grind up uterine tumors and suck them out and so you only have to have a tiny little incision instead of a huge one to take out that football sized fibroid we actually said that doing that inside a plastic bag that's labeled for intra-abdominal use does not require an IDE we made that decision the FDA came back to us and said you're wrong we think that plastic bag requires an IDE and I said yes sir but they did not cite us or inspect us or in any way criticize us because we had carefully thought through that and made our decision and documented it and thought about it carefully so these are challenging things to do I think the functional neurosurgery is a lot easier than the plastic bag for fibromas but we do take our job pretty seriously and if necessary we can get outside consultants and others to opine on particularly challenging things that we get I guess my final comment before we open it up would be hearing the case I was personally quite disturbed by the concept that somebody could reject CBT and I think our IRB would really choke a bit on that one and to say that we're going to go into a teenage brain where perhaps the parents have rejected a modality that might benefit this child that might be something where I would be thinking about an independent advocate a guardian, other ways to think about how we might treat such a patient in a multimodal way and the fact that you could out of hand reject something that at least from my knowledge is fairly effective in many different areas of psychiatric disease including things like OCD I would have some serious concerns about that and I think our neuropsychology folks would as well so I guess I'll stop there and maybe we'll open it up I'm hoping that we can pick up that thread in a moment but just before we leave you could you just say a word for the folks who aren't real familiar with consent in the context of research protocols when it comes to children and adolescents what the standard is I think in this case it would be one parent and the child a senting but could you sort of lay out the landscape for everyone? I have to look it up every time we do it because we don't do that much pediatric research but there's the 404 to 407 criteria in the federal regs that we need to look at in terms of minimal risk, minor increase over minimal risk and whether or not there's a benefit to the individual child or the group of children or for example children with Tourette's and we need to consider who consents and who ascends in that context and essentially if there's presumed benefit to the child and a minimal increase over minimal risk we can have one parent I think with more than minimal risk you need both parents and then we need to consider the ascent issue and certainly as a 15 year old we would always require ascent we generally stick with the sort of standard age of 7 being an age where a child can at least verbally ascent we usually in a study like this we would certainly request a written ascent process and we would also likely require that the child sign the full on consent form because our consent forms are supposed to be written at a 8th to 9th grade reading level so unless the child were severely developmentally delayed or some other reason you would expect that this 15 year old would actually be reading and signing an adult consent form. In just a moment I'm going to open it up but I don't want to lose the thread of the issue of whether the family needs to ascent to trying all non-surgical therapies before they can proceed to a semi-innovative perhaps part of a research protocol brain surgery and Paul I know this is partly a deliberate technique so that we can sort of pick that up and consider it are there types of reasons that the family could give that you think would be compelling and types of reasons where you think we would have to override their refusal of CBT or is it all one way or all the other way or? I perfectly appreciate that and you look at the paradigm of blood products for to hold witness patients and oftentimes they'll override a parent's objection. In this case if it's the core belief of the parents and the child is disposing this as a core belief do you think that cognitive behavioral therapy is going to be helpful in a child who rejects it and won't participate? Is it sufficient that a treatment has failed if a patient has been non-compliant or doesn't want that modality there's a certain even in epilepsy they'll say well they failed it because they didn't like the regimen of so many times a day they couldn't keep it track so I think one way to ask yourself is that what's the likely success so you ask the psychiatrist and psychologist even if they were compliant what would be the success and are you asking them to do a futile thing if not only do they don't want it if you force them to do it they won't really try or they'll only pretend to try and how successful is cognitive behavioral therapy if you don't try blood you put it in the veins and there this is a therapeutic relationship so follow me at the outset the interesting question for my mind is how persuasive convincing, coercive should the clinician be to get the child and the parents to agree what is the boundary between being an advocate as a physician and changing their mind for what you think is less risky, better and when does it become more central beliefs about talk therapy or behavioral therapy yeah I'll say what I know what our committee would do so I'll throw it out there and then we can talk about it we would probably do what Libby said, we would say that we're not going to proceed with this case if you don't try one of the gold standard first line treatments the habit reversal therapy is at least as beneficial as medications look at the effect size as it might even be a little more beneficial so they've been through a lot of medication trials with a certain likelihood of being effective but the whole other side the other first line treatment which might even be a little more effective they're refusing to do and it does come down to autonomy because then they're saying no I'm not going to do it we're saying you need to do it but at the end of the day they don't have to do it they just won't get the procedure and then just one other point I'm not going to do therapy I'm not going to do therapy they go to therapy I'm not going to do therapy the second session I'll kind of try this therapy the third session they're doing therapy so I think it would be worthwhile to kind of push that kid into therapy so I end up seeing the 0.1% of a population where best efforts fail and the ethicist comes in when there's intractable conflict many times so if there really is intractable conflict and you know that you have a window to help them through this developmental stage you're willing to say we're not going to offer you this potentially therapy during this window if you're not going to do this other therapy we're going to withhold knowing that you'll never try the best thing we're still going to withhold this second best thing that would likely be our committee's decision historically we've made exceptions sometimes if there's a really good reason sometimes we've had people I mean one way through this are people who either don't want to or aren't good at doing the behavioral therapy component they'll try it and they'll say it wasn't effective or their therapist will say they weren't motivated and then we say they try it there starts to be some gray area there same for ECT for depression we typically require we've had a few cases where the individual the individual just is firmly against doing ECT which we typically require before neurosurgery for depression and so we do take a case by case it is variable but most of the time we would require that they do the treatment with rare exceptions wonderful talk to say a quick question I recall a case when we do neuro pathology at the Boston City Hospital one guy had a bilateral you know proteinosis on the amygdaloids both sides and they report a curfew like syndrome licking everything in the bed before he died and my quick question is that when you mention you use abrasion to remove the central part of the output of the amygdalamus alphalamus I might have said wrong but it's a central mid place so there's still a lot of bearings on the side and my quick question is that what kind of adverse event after the cycle or neurosurgery mostly you'll come in and find the procedure is usually done while patients are awake they have a stereotactic frame all they require is lidocaine but you have the lidocaine where you screw the frame onto the skull the bone and the brain don't have any sensory neurons so all you really need to do is desiccize the skull and then you do an incision and retract the scalp and then you drill bilateral burr holes because of the frame and imaging you know an x, y and z coordinates within about a millimeter as to where you're going to put your tip and that tip can either be put in place and it's insulated except for the tip and you heat it up in a plate or it can be an electrode where you know where the tip is going and you leave it in place patients are awake and they usually go home within 24 to 48 hours yeah so it's actually a pretty standard procedure with low risk but not no risk patients will experience seizures one percent of patients will develop an infection those rates are no higher or lower than craniotomy for any other purpose whether it's for hematoma evacuation or AVM fix but you do have that risk but other than that other than the standard craniotomy risk there's no higher than other craniotomies therefore the psychiatric indications are you doing postoperative adjustments of which leads are on you know what the firing rates are yeah I could describe that as well that's quite intensive what we have is bilateral we have electrodes with the tip at a specific target and each electrode has four contacts and each of those contacts is going to hit different fibers of passage that connect brain networks different brain areas and the idea for DBS is to hit white matter fibers of passage in a circuit because it allows us to better affect the whole circuit instead of just one node and there's anatomic variability as to where people's fibers that connect different brain regions are so we have to spend three to six hours usually in multiple sessions exploring each of the different electrode combinations at different frequencies pulse widths and amplitude and 90% of the time we'll try settings and nothing happens and the 10% is really where the money is because then we'll see either adverse events stimulating the ventral contacts for psychiatric illness can cause autonomic symptoms and fear heart rate you've probably seen that before Paul and we also find the ones where they say oh wow I feel better and it's pretty dramatic these people will say oh I haven't felt this good in 10 years and we're like bingo and we'll identify a few of those and the one with the biggest effect is plan A and we'll leave it on and chronically stimulate the ventral contacts and most of the time that will be effective but if it doesn't we have from having screened the entire parameter space we have other parameters that also had beneficial effects and we can then move to a prolonged trial at plan B, C, etc Thanks my question is for Dr. Ford I wanted to ask you if you could say a little bit more about core beliefs which you raise as a way to sort of out the case with wanting to reject cognitive behavioral therapy but I'm curious what is the core belief and how do you sort of distinguish that from other beliefs and why does that what does that matter So I used the language of core belief opposed to religious belief because I take religious belief for many people to be an expression of their most central beliefs that they don't want to violate so think about those things that you're not willing to give up willing to give up very little of in order to accomplish other goals So how do you tell when you talk to people you know this is what I think our conversations are often what are you unwilling to risk you know a patient, a Parkinson's patient who said his favorite thing to do was to tell stories to his kids if he can come to Sartre because of the surgery he chose not to move forward it was so core to tell his grand kids stories that he didn't want to interfere with his voice Joel the witness what I often think about is that some people in Joel the witness phase their core belief is not to have blood problems so we picked up on my language of core belief because I want to sort of expand it to say the things that center us and that we want to that we all want to violate in one level that we should respect The case is written in an interestingly intricate way the kid sees the thing on television and says I want this surgery you've got a developmental window for his adolescent development to be sure but you also have an adolescent window of their ability to interpret the news so the kids now pushing for it the family brings him reluctantly the parents bring him reluctantly and the text says the family doesn't believe in CVT now I don't know what the kid thinks about all this and of course it's almost impossible to figure out what the kid thinks if the parents are saying they all feel something else and I mean he's not a emancipated minor he's a kid brought by his parents I don't know who's running the show here but I feel very uncomfortable as many of you do in this juxtaposition of things complicated I must say the decision making process I found it absolutely fascinating so if the rest of the group doesn't want to go to the core values I can't understand but whose core values count the 15 year old or the reluctant parents so the answer is yes and yes so in our in our setting we also have multidisciplinary committee that I'm a member of we have neuropsychologists we have psychiatrists we have neurologists we have physicians and often times they will bring a case like this to the committee for discussion and then we'll have a variety of us talk with in this case the kid his parents to try to get out how do we balance not just the core values in any one person but the core values of the team the surgeon needs to balance his value of a benefit for a social benefit right so that it's a great question you have to talk to people to see where that intersection is maybe there's an intersection between the child and the parent but not between that mode that node and the team and so it may be that this is the wrong center or maybe the team has an obligation to convince them otherwise an obligation to send them to another center that their core values may match up but the answer is each member where on the table the patient the parents all are moral agents with different roles and obligations and responsibilities depending on where they're sitting in which hat they have on and we need to find a way to talk with these and come to an agreement and transparent about the justification and consistency from this patient with assurance with this patient with insurance so this was not my actual question but I want to follow up with you Sai I think you were pointing a little bit to the difference between the core values of a 15 year old and the core values of the parents so we've had cases in which we've allowed 15 year old to refuse selective brain surgery for eliminating seizures that his parents very much wanted him to have and the question here would be could the child ask for something and could his parents be the veto on the basis of their core values thinking maybe that his core values aren't really deeply grounded in the same way that perhaps his parents are is that what you were trying to get outside the difference between the parents that's part of it where this question comes up for me is when you have a standard temporal lobe epilepsy lesion with MRI abnormalities the spec scan everything points that the state of the art best thing for this kid is to get this you know that standard at least one randomized control trial only one but the ideal candidate when it's an innovative neurosurgeon I think we hold this to a different standard and I think that all parties have to be in some agreement this is really the best interest of this child because the very decision making questions that you don't think you can demand in that way you bring up a really interesting question let's say the whole resistance to the behavioral therapies of the parents and the kids gung-ho he would try it out is there a mechanism by which you can offer cognitive behavioral therapy to the kid against the parents wishes I don't know but that's interesting right because then you first of all it complicates the matter because you have different opinions within the family but the patient wants it and then how if you can can you get access to said therapy to a minor against his parents wishes I don't know the answer to that against the parent he comes home after a very successful session and his parents do nothing but stop and how effective is that yeah could also they could undermine it so in some states in Ohio is one of them adolescents can get psychiatric care for a limited amount of time without a disclosure of their parents for alcohol drugs and certain psychiatric implications as well as a reproductive now the question always comes how do you do that and for the parents not to find out and is that really going to be effective so I think it's this nice set of questions good questions I'd love to hear a little bit more about what we think would constitute sort of genuinely informed consent in this case and what the obligation of the care team looks like so we've talked a little bit about the difference between the expectations of the parents and the child so maybe one obligation would be to bring them a bit closer together and the expectations but what about risk then what would it take to really adequately inform this family about the risk of the surgery so there's been nine published cases of this do you go through each kind of case with them and describe the different situations behind these cases or do you just kind of say look we really don't know given the evidence we have what the long-term risks are and maybe we don't really know what the short-term risks are either given the limited evidence we're working with I can address that if you guys want me to so for the OCD cases it was approved by under an HDE based on 26 open-label study of 26 patients and so this would be nine instead of 26 and what we have in our consent form is because that's not a large number we also include the risk associated with DBS for we just think for relatively equivalent procedures so we present the known risk for a much larger data set for DBS for other indications so just putting an electrode at a target but a target non-specific we include in the risk risk section the ablated procedure risk because it's another craniotomy for this risk and then of course we include any of the adverse events that were reported in those 26 patients and then every year when we do our continuing review if there's any new evidence that's come out or any more we have to add so that it's constantly updated and so that's how we handle it and it's actually a pretty long section we also for these psychiatric indications require a third-party independent consent monitor to be present and they attend the session and then we leave the room and they have a formalized weighted debrief to make sure that understanding was there for this you know more vulnerable population with psychiatric illness so that third-party consent I'm not sort of under so I do some of that I'm not really third-party but I'm also not paid for through the Neuro Institute I'm paid for through the Chief of Staff's office and so I have an independence although not complete independence but they employ sort of not employ they have me meet with many of their research subjects for OCD and previously for depression they try to give this even-handed discussion not try to convince them not to have surgery but one technique I would use in this case is that the highlight to them nine cases are reported in literature in general the literature tends to report the positive the more positive cases so we can't assume there's a lot more but anecdotally we know there are others and we have to realize that those others may be worse in fact so maybe I lay crape a bit it's my job to tell them that I can send to say that news story you saw those magical stories are not the typical and even those folks the literature say still struck it's not that they're magically cured it's to help the child and the parents assess that there is genuinely unknown risk and it's probably not as good as what is and if the thing were to come to the full IRB the full study we have the option to acquire an advocate an independent person to fulfill that role to be consultant to the patients the families an advocate can have different roles either sometimes to educate, assess inform independently they're often very sophisticated individuals they often have psychiatric or ethics training formally so they can really assess understanding and vibes and the like very uncommon that we actually mandate that but occasionally we do an example of a case where we did that was the total artificial heart study way back when that was done at one of our institutions which is actually a Massachusetts company had actually built that into their project and the person was a physician who had psychiatric training and they actually were paid to perform that role I have a quick clarification question Darren you mentioned that the protocol the procedures that you've done were not done under a research protocol and the consent process being using a document that gets continuing review each year which suggests that that is an IRB approved consent form I'm glad for the clarification that's for the OCD cases which is IRB approved under the HD for the Tourette's we handled it as a standard clinical consent Hi, thanks I was wondering if you could say a little bit more about what special role if any DBS is playing in this case or is it kind of a placeholder for any innovative neurosurgery say if it was Gamma Knife would you think about the case similarly for example often one thing that's brought up is people say well DBS that's more reversible than some of these other surgeries That's a good point, do you want that or do you want me to highlight it's a reversible but also modifiable Gamma Knife you drop it in and expand or even the other way of surgery you're difficult to reverse so people are less hesitant perhaps to do put this in knowing that it's probably going to leave a small lesion even though there's infection risk and so it pushes the risk assessment so maybe it's a little more permissible to think of burning a hole in this kids brain but maybe a little hole with lead in it might be justified Yeah, micro lesion during implantation which usually has no clinical sequelae and then it's reversible for a kid I think you would want to go that way it's interesting though in the cases that come to our committee about half the people we give options to do in a blade or deep brain stimulation half of the participants or the candidates say you know I really like the idea of this being able to take this out if it doesn't work and just return to normal I don't want to have a lesion burned in my head that's not reversible I like the idea that there's parameter space that you can explore instead of binary just you have tissue or you don't and that's perfectly reasonable then we have people who say wait if I have deep brain stimulation you have to leave this in my brain the rest of my life and I have to come in and have it adjusted and sometimes you have to change the battery and I have to undergo general anesthesia I'm thinking I like this one and done deal and so it's very interesting people and I think they're both entirely reasonable conclusions but people it's funny how people tease out into one or the two and we typically typically they're eligible for one or the other and we just usually you know respect their wishes and do the procedure that they choose I just had a quick question about your thoughts on the sort of responsibility or ethics of the manufacturer in this case it was just sort of surprising to me that you haven't after all this experience don't have as much systematic evidence about these patients to to provide to this patient because of you know it seems you know it's entirely dependent on your publishing your experience with this and not the manufacturer who that is you know getting the profits from this device being implanted maintaining its own registry or helping in this process at all and just I guess I was just interested in you know if there's any role I mean I know that there are some responsibilities that HDs then give to manufacturers to do studies and stuff like that and I guess I was just wondering what their relationship is with all this. Yeah they're really only on the hook for things where they have the FDA indication and if any clinician uses it off label they're off the hook just to same with medications. So equally though I think that there's a really interesting initiative with the brain initiative and NIH part of the reason that you see this is it's very difficult often for individual clinicians researchers to use to get an IDE on a device that's already been approved because they need to get a letter of right of reference from the drug company or manufacturer that will allow the FDA to use the past data so if you're a surgeon who wants to say I'm going to do this the best way I'm going to do this in a rigorous trial the amount of paperwork and negotiations with a big company is incredible it'll never happen there's initiative right now with the NIH and the brain initiative that devices that already have one indication that they'll standardize the legal agreements the intellectual property the right of references they try to fund and encourage individual researchers to do something like a new indication so the protect liability of the company it's not an indication it's going to be enough to justify the millions and millions of dollars of research but also gives them an opportunity to stand aside and let the individual researcher get NIH funding and actually do it so there's this disincentive that we need to remove if we expect people to do more research that's individually do oh yeah right on target and I know you went to the industry NIH I think that was essential to that now this is a morass and the companies view it as just a downside for them and you know we've spent a fair amount of time wrangling with some of these companies to let us do things even do things that seem like no brainers like putting somebody's replacing somebody's battery and you know who's benefited from one of these devices so this is a really challenging area and I might add the right to try legislation that's coming forward which kind of blows my mind as a physician where they're saying you know and this is moving forward in a number of states where you as a patient have a right to demand access to certain therapies or devices and there's no consideration of you know what it would actually take a caregiver would actually need to do how this goes through the FDA who bears responsibility the manufacturer, the investigator the patient so it's sort of a clash of cultures and very challenging area to negotiate so I have one last question but I want to just tell everyone that we do have dinner available at 6 in the modell room which is right back behind this auditorium all are welcome whether you told us that you wanted to come or not whether you knew about it beforehand or not we'll have enough food for everyone and it'll be a chance for everyone to continue the conversation in a slightly less formal fashion sorry webinar participants you can't come to the dinner so Darren when you first said that we did these procedures for the Tourette's cases outside the context of research I bristled said really you aren't contributing that research to the field and then I was mollified when you said that you published the cases and they agreed to publish the cases so I'm curious maybe this would be an unusual family but if you had had a family that said we don't want you to share information about us with other centers we don't want you to publish information even if it's de-identified I could imagine if I were in the position of doing this surgery I might feel tempted to insist that you allow us to share de-identified information about your procedure just because it's this is novel other people are doing it and they need to benefit from this knowledge what's your take on that? it's a real tension because you're giving the individual patient opportunity and access to a treatment that's not often available we wouldn't be offering unless we thought it was helpful so we're giving them it doesn't mean that there aren't unpublished cases and maybe it's literature looks better than the real deal but still we're offering that and it seems it would seem somewhat petty for that individual completely de-identified to not allow us to share that to help with the general good so we would be bothered by that but at the end of the day because we're doing it for clinical care we'd have to just bite the bullet swallow and offer the clinical care but it would be a tragic loss of information for the scientific literature but we would not let that deter us from going forward for what is primarily a clinical indication so does it change your mind if the patient and their family doesn't have insurance and you've cobbled together your resources that you could give to one family to give them access you've gotten the device company to donate it doesn't make any difference to their obligation to share it if you now have the opportunity to give them the resources and when does that become unduly coercive and an invasion of privacy yeah I have to take the patient who's in front of me so that would be my answer and sometimes to do that cobble like can we please have a free device hospital can we still please have some free or time but you have to treat the person in front of you so I think you just have to take the hit so we are right on time that was a perfect ending to I think a really terrific session I'd like us all to thank our speakers for a great seminar