1 >> Ran Gilad Bachrach: Delighted to host here today Dr. Dennis Turk. Dr. Turk is a John and Emma Bonica Professor of Anesthesiology and Pain Research and Director of the Center For Pain Research on Impact, Measurements and Effectiveness at the University of Washington School of Medicine. He was previously he was previously associate professor at Yale and professor at the university of Pittsburgh School of Medicine. He's a founding member of the American Pain Society. Dr. Turk is a fellow of the Academy of Behavioral Medicine Research, Society of Behavioral Medicine and American Psychological Association. Dr. Turk has been active for many years in organizations and is past president of the member of the Council of the International for six years. He is a special government States Food and Drug Administration. national and international American Pain Society and was a Association for the Study of Pain employee advisor to the United He has received a number of awards, including recipient of the Award for Outstanding Scientific Contribution. He's contributed over 550 publications to the healthcare literature and is currently editor-in-chief of the Clinical Journal of Pain. Dr. Turk has authored 20 volumes in the areas of pain, chronic illness and clinical decision making. Going over the list of all your achievements and awards will take the entire time slot. So I think I'll stop here and give you the stage to talk about chronic pain, technological challenges and opportunities. >> Dennis Turk: Thanks, Ran. Thanks for the nice introduction. All that means is that I'm old. I got gray hair. The longer you do things, the more degrees and awards and stuff that you get. I've been given an interesting and dubious task, to speak to a very different audience than I'm used to speaking to, to try to talk about, get you sort of a brief overview, but fairly quickly, and I talk quickly, you'll notice, on what do we know about chronic pain. What's the current status, current situation. And then to talk about hopefully with us, but don't. One definition less and less until he challenges and opportunities that are available to you, you because you have the technological knowledge that we of an expert is someone who knows more and more about or she knows nothing about everything. 2 And I have thaw distinction on the pain side, but we can flip it around and have the distinction that I know nothing about the technology and the future of what's going to be happening, and you guys do. So in a sense, I'm the worst of both worlds. I know nothing about pain and I know absolutely nothing about the technology. So given that, it could be a very short talk or a very long talk. Let's see if I can sort of catch you up. You though, ask the experts. And if you ask the experts, the only thing they'll agree on is that the third expert is incompetent, and you'll notice that one of the experts you have here is in the picture. So I'm going to try to demonstrate I know a little bit something about at least the first part of this talk and hopefully won't discourage you from listening, because I think from my talking to some people already, it would be nice if we had real simple answers to things, and unfortunately I'm going to make them more complex than simple, and your task is going to be to figure out how can you take that complexity and get it down to something that's manageable, given the technologies that you have. And you have tremendous opportunities. So it is a great pleasure to be here to speak to you. So let me tell you a little bit about pain, just so you understand the ground work. And I'm going to be talking about exclusively about chronic pain. And chronic pain is usually defined as pain of six months' duration or longer and beyond the expected period of healing. So, for example if you injure your knee and we expect you to be healed within six weeks and you're still reporting pain in three months, that's begun to become a chronic problem. However, it also could be the case you have progressive disease. So, for example if you have arthritis, it might be progressive over time and it will get progressively worse. So those are chronic conditions. Anything beyond the expected period of healing or three to six months is what I'll be talking about. And I really am not going to focus on children, and I'm not going to focus much on cancer pain, but a lot of what I'm going to say conceptually is just as relevant for pain associated with cancer and any non-cancer related pain. And you'll understand the kinds of pains I'm talking about. 3 So just to give you some big overview picture, in case you were thinking this is a small problem or if you, yourself, have the problem and thought you were alone, I think you'll find out very quickly you're not. Nearly one half of Americans see a physician with a primary report of pain each year. One half. So if you look around the room, assuming that this is a normal distribution of population in the United States, about half of you, when you go to a physician, pain's going to be the symptom. And this is separating out your normal annual visits, but just when you go to a doctor, why you're there. Usually, pain is one of the major reasons. The proportion of all physician visits, just for back pain, which is the most common kind of pain in the United States, with arthritis being second although back pain and arthritis you could have back pain associated with arthritis, so it's a little tricky to say that. But back pain alone accounts for somewhere in the neighborhood of 20 million visits a year to physicians. And approximately, if you think what's the impact of these numbers have on the real world, 149 million work days are lost each year due to back pain. So if you think about the time, you've ever had back pain or you know somebody who's had back pain who hasn't gone to work, then you'll understand what these costs are. And that's estimated to be almost $20 billion in just lost productivity, lost time on the job, other people filling in for you, et cetera. We can look at different pain conditions. Arthritic pain, back pain, migraine headaches and cancer related pain. And approximately 35 percent of the U.S. adult population or, roughly 100 million people are predicted to have some type of chronic pain. The United States is not different from the rest of the world. Somewhere in the neighborhood of between 19 and 35 percent of each one of the European countries that this has been looked at also reports significant pain problems. And usually, that's pain sufficient, depending upon how the wording of the questions are, to impair some activity you're engaging in. So it's not just oh, yeah, I have a pain but I do everything I'm supposed to do. It actually has an impact on your life. And you can see the relative proportion of the different types. Remember, I said arthritis is going to potentially also be back pain. Although back pain is the most common part of that, may be captured in the arthritis 4 world. But those are millions of people, so it's a lot of people. And if you've got family members, if you, yourself, have a pain problem, you're talking about one third of the population. And if we want to look at this by age, this will make all of you people feel very good. It's getting worse, because as you age, you're going to see that the frequency or the prevalence of having some type of pain increases proportionally, and it's going up nicely. It's not going down in any way. So any of you in the room, depending upon where your age, you can see where you are on that, males versus females. And in every instance at every age, females tend to report more pain than males do, and we can get into lots of interesting discussions about why that may be. If you want to ask me about that later, there are some speculations that we could talk about. But there's no need to. Population is aging. So everybody in this room has this to look forward to. If you make it to age 65, the likelihood that you're going to have a pain problem is about 75 percent. If you get to be 85, it's more likely to be 85 percent so if you live long enough, you're going to have a pain problem. >>: Why did the male figure go down? >> Dennis Turk: They're dying off younger. that's what's happened. >>: Hate to give you bad news, but I used to think that the female have children so [indiscernible]. >> Dennis Turk: Wrong, in that there's not good evidence one may or another whether they're more tolerant. However, part of the problem is in how people report and how men and women are treated in society and how they respond, how they report symptoms. When it cluster minute, because comes to pain in treatment, in every medical condition except for headaches, the prevalence is more high -- I'll get your question in a is higher on women than on men. But that's in clinical populations, women more likely come for treatment for their problems than men do. So if you do a community survey, the difference between males and females isn't nearly as great as it is in community samples. Yes, ma'am? 5 >>: The label that you have on the graph, 95 percent CI. >> Dennis Turk: This is -- that's what that is. confidence interval. >>: What is that? That's referring to the Okay. >> Dennis Turk: And if you want to look at some other conditions by millions of people, there's just some more numbers. This is to give you an idea, compared to some other conditions. So strokes, blindness, visual problems, diabetes, other problems. By far, the largest percentage of people have pain problems. So everybody gets very exercised about cancer, by the way. If you noticed several slide back. Cancer and pain is very dramatic. You'll notice proportionately, that's a small peanut compared to what these other chronic pain conditions are. And that's, again, 33 percent of the population has some type of joint related symptoms. So arthritis is definitely a big and important player. That's arthritis, OA, osteoarthritis is very much related to wear and tear on your body. So all you healthy people who are jogging and doing all those good things for yourself, trust me, you're going to have arthritis problems if you don't already have them. So what's the annual cost? Given these numbers, what does this actually cost a society? That's estimate per year. Anywhere from 560 to 635 billion dollars a year is spent on health-related problems, related to pain. And we can look at it compared to other kinds of conditions. So again, these are different medical conditions, and here we're looking at cost. We're going down to chronic pain, which I haven't filled in for you, and chronic pain. And if with we go up to include indirect costs as well, there's that 500 billion dollar number. So you can look proportionally. Again, look at cancer, which everybody gets very exercised about. Look at proportionate costs, and that's because of the denominator. It's much fewer people are going to have cancer than have some type of chronic pain. So it's a big problem. 6 So given that big problem, of course, we would assume that we can take care of these people very well. A couple of saying we have good treatments for pain and I'm going to hopefully -- not hopefully. I'm going to convince you, I think that we don't have such good treatments for pain. But what are some of the impediments to people getting good treatment for pain? Well, it's often viewed as a symptom and it's secondary. So it's not a disease. So therefore if you go to the National Institute of Health, there is no Institute of Pain. There is a National Institute of Arthritis, Musculoskeletal and Skin Diseases. There's a National Cancer Institute. There's a National Heart, Lung and Blood Institute. Those are disease-specific. So the reason pain doesn't get the attention is people get very concerned about the disease, and they want to cure the disease, but they tend to forget that almost all of the diseases that are particularly important have pain as an important symptom related to that. There's little consensus about how do you treat people with pain. If you go to different medical specialists in different parts of the United States in different parts of the state of Washington, you'll get different treatments depending upon who you go to. In different states in the United States, there's a ten-fold difference in the number and types of surgeries you get for back pain. It's highly related to the number of surgeons available. The more surgeons, the more likely you're going to get surgery. Does that mean that you really need it? That's some of the discussion. Inadequate knowledge by the primary providers. How should a primary care provider, we were talking earlier about the typical primary care provider, you're going to see, has estimated that they're going to have 7 to 15 minutes of time to spend with you, and assuming that they have 35 to 40 patients to see in one day, how much time do they have to spend with you to talk about your chronic pain problem and the impact it's having on your life? So there's not a whole lot of knowledge about how to handle it, and they don't have the time. My colleague who is sitting over there, [indiscernible] Patel's wife is a pediatrician. She doesn't have time to deal with these complex problems, because she's got to get you in and out pretty quick. And imagine your appointment is for 8:30 in the morning and you have a chronic 7 pain problem. What is that going to do to the rest of the schedule for the rest of the day? So when you're waiting and your 4:00 appointment is turning out to be 6:00 at night, now you know why, because somebody shifted -- and it's not likely it's the physician's fault. It's likely what the presenting symptoms are that created a problem. It's perceived as very time-consuming. It takes a lot of time to see these patients and a lot of primary care providers want you out as fast as possible. There's a lack of really trained specialists, except if you're in university medical centers or large cities. So if you happen to live in the Yakima or Walla Walla, there's not a whole lot of specialists in pain care. You have to come all the way to Seattle, which is a problem because it's a long trip. Chronic pain, by definition, there's no cure. Chronic means it lasts for a long time. Forever, potentially, as long as you're going to live. Therefore, you're going to have to keep coming back and forth across the mountains to see your provider to deal with your pain, and that's part of the problem. You look at the distribution of the United States, pain specialists are in big cities and universities. They are not in rural areas. Prohibitive costs, specialty trained treatments are expensive and a lot of insurers don't cover them. So even if we know what all the appropriate treatments are, it doesn't mean that the insurance companies are going to pay for those. That includes different types of medications, different types of surgical intervention, different types of other types of interventions. Geographic distances to travel to get to specialists, it's very costly for people to have to come from Yakima to Seattle. It's time off of work. It's travel time. And in addition to the healthcare cost, there's those indirect costs. And there's no cures. There are no cures for chronic pain. And make you feel worse, there are no cures anytime in the future you're going to see for chronic pain. I've been doing this since my hair was black. If you can't see my hair, it's gray. I've spent approximately 30 some years working with pain patients. The same patients I saw 35 years ago are essentially getting the same variations of the treatments that they got 35 years ago, and they're still waiting for the cure. And if I came back here in 35 years, that would be nice, I think I'll be giving you the same message. 8 We'll have some more technological advances on how to do the surgeries and different medications may be developed as variations of the same classes. I think I was telling somebody this morning, I forget who it was, Matt or Randy, but what's the most potent medication we have right now? Opioids. When were opioids first found and used? In the Ebers papyrus in 4 BC was the first time there was reference of using opioids for headaches. Nonsteroidals, aspirin, Aleve, these kinds of drugs, they're based on acetylsalicylic acid. Willow bark, Hippocrates used willow bark for pain in 400 BC. So we haven't gotten very far in the major classes of medication. There are two other classes that have come along that are slightly improvements on what we had 400 to 4,000 years ago, but they're not that much better, as I'm going to show you some data on. Functional disabilities for a long time, and they're going to limit your ability to get to care. So an important thing is if, in fact, you have a chronic disease, a chronic problem of any kind and you come into a rehabilitation type of facility and we provide you some type of treatment and we didn't cure you what does that mean? And what that means is that people are going to have to do a lot of self-managing over a long time. So if the average age of a person who has a chronic pain problem is 44, which it is, if you look at people coming to pain specialists, that means they're going to have a long time -- they're not going to die, typically, from chronic pain. They may be living 30, 40, 50 years with a chronic pain problem. How are we going to treat those people over that time if we don't have cures? And we'll get to that when we talk about some challenges that may be available. What are some of the assumptions that physicians and probably lay people make that are important to think about, and this is probably an over simplification. It assumes, by medical perspective, that there's a close correspondence between the objective pathology, the impairment, and the amount of symptoms or the impact it has and disability. The more pathology I have, the more pain I should experience, right? And the more pane I have, and the more impairment I have the more disabled I should be, right? There should be a close association. There's not. And we can understand that. 9 It assumes that if and when the symptom generator, the cause or the symptom is identified, the treatment is going to remove it, cut it out, cut that nerve, cut out that painful body part, or we take some medication to pharmacologically block the signals. Pain signals have sentry information from the periphery of the body, go centrally and the brain is where we interpret something as being painful. There's no pain with no brain. If I have you totally anesthetized, you go for a major surgery, do you experience any pain during the surgery? How would we know? Can I ask you? You're anesthetized. Can I measure some physiological responses? They're not related. Can I observe your behavior? You're totally anesthetized. So how will I know how much pain you have? So therefore, we don't know, but the assumption is that when you're totally anesthetized, you don't experience any pain. So therefore, that requires a conscious organism, conscious human to report on their pain. It assumes that patients with the same symptoms and a diagnoses should be treated with comparable intervention and have the same outcome. Two people, same problem, same sorts of pathology, assuming we can find something. We treat them the same way, and they should have the same response, right? It's not true. Same people have the same diagnosis have the same surgical intervention performed by the same competent surgeon in the same successful way will report very differently on whether they got a benefit from that surgery. Less than 20 percent of people who have surgery for back pain report that they're pain-free after the back surgery. It assumes that the symptoms that persist, despite appropriate treatment, are likely psychologically caused or psychogenic. If, in fact, we blocked or cut the pain signals, pathways, how could you have any pain? So if there's no physiological basis, then it must be, ipso facto, it's psychological. Psychogenic. Second gain, because I want to get insurance payments. I want disability, or I want to receive medication that have euphoric effects, like opioids can. So that's an assumption. Now, are those assumptions valid? No. And I'll demonstrate this to you, and I'll show you just shortly that an assumption is 10 that patients objectively determined equivalent degrees and types of pathology vary widely in their reports of pain. Three of you here, I put you into procedure, I get widely different the same stimuli, electric shock, hurting you. If we try those and we'll get a wide variation. a laboratory through the same pain induction responses. Now how could that be? If I do heat, cold, we've got a lot of ways of I bring any two or three of you in there, There were some funny studies that I always like to mention back in the 1960s in which they brought people into laboratories, college students into laboratories and did some kind of laboratory induction of pain, and then they would say to the students, you know, you Yale students, people at Harvard, for some reason, we don't understand why, their tolerance for pain is much higher. And then they redid the test, and what do you think happened? The tolerance went up. And then they told the people from Stanford that the people at Harvard had -- and the numbers went up. And then they told the males that the females, and vice versa. And then told Catholics and Protestants and Jews and they went around. And every time, in every instance, the instruction led to changes in how people reported their willingness to tolerate pain and their thresholds for pain. Lots of variation. Asymptomatic people, people who don't have symptoms of pain, often reveal objective evidence of structural abnormalities. You see all the different kind of imaging procedures and I'll show that to you. This is -- this graph is showing you, these are lumbar myelograms, CT scans, disco grams and MRIs. These are asymptomatic people, and these are what they found on those different laboratory procedures. So for example, 24 percent of people who have no symptoms, who had lumbar myelograms, had sufficient abnormalities that you would expect that they should experience pain and you can see the different numbers. These are people who have no symptoms. So you've got pathology with no symptom. How would you understand that from that traditional model of pain, that there should be a nice relationship? 11 Conversely, patients with minimal objective evidence of pathology often complain of intense pain. So on one hand, you've got people who have pathology and no pain. Then you have people with pain and no pathology. So I guess -whoops, I guess what we must have is a disease deficit disorder. Can't find anything wrong with you. So here's the fundamental problem that we have. We look at these individuals, and the patient reports back pain, and we look at their spines, it's an MRI, and that's a perfect -- you're not radiologists, but that's about as clean as you could possibly see, okay? Then we've got an asymptomatic person who shows significant constriction on the nerve, which if you saw that and you were a radiologist, you would predict this person's got significant pain. But they may be asymptomatic? How could that be? 86 percent of people with chronic back pain have normal MRIs. 86 percent of people who have normal MRIs report back pain. Are they all faking? They're all making it up? How could that be? 30 percent of people with abnormal diagnostic images do not report any pain. So you've got these numbers, they don't make sense if you take that traditional, nice, physical model of pain. So some more challenges for us, surgical procedures designed to inhibit the symptoms by severing the neurological pathway, cut from the periphery up centrally to the spinal cord to doing phlebotomies, which we've done as of the 1940s to try and prevent pain, and it didn't cure any problems. So you've cut the nerves all the way up, how can the signals be getting to the brain? How can you experience pain? How come you're not anesthetized? >>: [indiscernible] so as far as I understand from the pain system is [indiscernible] another system of the body [indiscernible] this is the purpose. >> Dennis Turk: You put your hand on a hot stove, you pull it off. >>: That's right. So it's supposed to surface. In some cases, people indeed have some problems, say [indiscernible]. In some cases, I don't have any problem, but I reported pain. So that means that I might have a problem in the pain. 12 >> Dennis Turk: You're mixing up pain and chronic pain. Acute pain, that reflexive response, everything is working the way it's supposed to. Over time -- let's say back pain. Say you had an injury. We can see the injury. It's the acute phase. You've now recovered, and most of the time for any kind of back injury you're going to have, work in the garden and hurting yourself, it's going to be gone in a couple weeks. So the pathology's gone. The pain system is still somehow operating. What is causing the pain system to keep firing if, in fact, the pain generator is now resolved? And that's what we don't know. >>: So this is what I'm suggesting, that the pathology is the pain system itself in my back. >> Dennis Turk: Exactly. Well, the pain is never in your back. It's always in your brain. But yes, the pain system is altered and that's sometimes referred to as central sensitization or the plasticity of the nervous system. What's changed now is not the periphery. What's changed is the nerves and there's something going on that's refiring and people have looked. Remember, if we keep cutting the nerves, where is that system breaking down? We can't do a total brain removal, lobotomy and thalamotomy, those are pretty extreme surgical procedures and people still report pain. >>: Do they work? >> Dennis Turk: They don't. They don't work, because pain's distributed -- if you understood the pain system, it's widely distributed so you couldn't remove enough chunks of the brain to get rid of it all. So the pain -- there's a theory. This isn't well proven. There's a theory that there's a change in the nervous system that's perpetuating these signals getting to the brain or being recorded in the brain, even though the initial cause of the pain is no longer present. And if you look at the example of phantom limb pain, someone will have an arm removed, and they'll report pain in the part of the limb that's not there. So something is changing upstream for them. So you're right that that's what people are trying to understand. We've been looking for the last 20 years on this central sensitization theory, and we're not getting too far. So hang in 13 there. Have me back in 20 years and maybe we'll be able to answer it. The key dilemmas, there's modest associations with the impairment, pain reports, disability and response to treatment. To give you an example of this -- I'm going to skip that one for now. So this is a person who's had above the knee amputation. No question about it. This person has an impairment. And an impairment is an objective alteration, functional or structural aspect of the body. Structurally, they're missing a limb. No question. That person impaired. Is this person impaired? Well, he's impaired, but he's not disabled. Skins Randy's here and he came from Israel, I'll refer to Itzhak Perlman, who is a very famous violinist who some of you may know of, concert violinist, internationally known, who had polio when he was a child. He had very heavy braces on his legs and uses of crutches and canes. He was asked by a journalist if he thought that having polio had interfered with his career in any way. And his response to them was, if I played the fiddle with my feet, it would have interfered with my career. Is he disabled? I'm sorry. Is he impaired? Absolutely. Is he disabled? He would say no. So there's not equal. You can't assume that these are going to be the same thing, which is what our key dilemma is going to be. You're always stuck, and I was talking to Ran this morning. We always have this dilemma of how do you know how much pain someone has, and how do you decide whether you believe that or not. Because we really have this fundamental problem. Self-report scale, on a zero to ten scale, rate your pain so I got a verbal report from you, and then I can look at that x-ray, that MRI, and lo and behold, and you've got facial expressions. So what's the relationship between the self-report, the physical pathology and the facial expression? Everybody would guess this guy is experiencing some pain, right? So what's the relationship? Okay. Well, what we find out, unfortunately, they're not highly correlated. Well, if they're not correlated, what are you going to do? Which one's right? Do you trust the report, do you trust the x-ray? Do you trust the face? And this is the dilemma that healthcare providers have had and insurers have and 14 attorneys have and disability claims people have, because how do you know? I know by what people tell me, or I know by their behavior, both of which are under voluntary control of the person who experiences them. So can I trust them? Pathology says they've got nothing wrong them. But the patient complains of a lot. He or she's faking? Look at their ratings, and it looks like they got real pain, but their facial expression may be more stoic. So which one do you believe? And this is the problem that I have for the last 35 years but everybody has had sips the beginning of time. How do you know how much pain somebody has, and how much do you believe them? So what's an unintended consequence? If we've got all this pain, it's so costly and we're not treating it very well, well what's happening is we expose patients to increasingly invasive diagnostic treatments, procedures that are iatrogenic in and of themselves believe it or not, CT scans, exposure to significant amounts of radiation. Giving you plane x-rays give you a significant amount of radiation. PET scans, if I would show you those, we're injecting radiographic material into you. These are not benign procedures. False positives and negatives lead to inappropriate care. We see something on the x-ray that could be related to pain, and we treat it. But I just showed you that 30 something percent of people who have abnormalities don't have any pain. So how do you know there's a correlation, pain report and the x-ray, but they don't necessarily fit together. So how do you know you're treating the right thing, or is it a chance finding? Contribute to patient passivity, frustration and continuing quest for cures. You keep searching for the next one. And when you have nothing better to do, go on Bing and put some pain conditions in there and look at all the desperate people telling you about all the things that they need and they're not getting treated. We got a lot of people -- 30 percent of the U.S. population. Adult population. The Ds. Deconditioning, deterioration, depression, disability, and demoralization. This is how I spend my time. This is who I see every day at my job. And you want to know why I got gray hair. That's why. I'm really only 30 years old. We divert resources, time, effort and we get away from self-management, which I'm going to come back to, because I think that's where you have a tremendous opportunity to help us. Self-management. 15 If, in fact, we can't cure these people, if, in fact, they're going to have symptoms for long periods of time, then it's dependent upon the person -patient, if you will. Patient when they're in my office, person when they're out there, to do things to make their lives better, to function even if we can find something to reduce, if not eliminate, their pain. There are a lot of different treatments out there that are tried for people with pain problems, and I'm not going to go through all the details. My favorite is the sulphur mud baths that we talked about, which is a treatment in Germany for fibromyalgia, which is quick successful, but we don't understand why. There's a lot of different treatments. Everything from pharmacological, surgical, nerve blocks, pumps, implantable pumps and stimulaters. Electronic systems put into the body to block symptoms of the pain, not only spinal cord stimulators, it's inserted into patient's back. There's a generator that looks like a cell phone. There are wires that are tunnelled up along the spinal cord. There are electrodes on the spinal cord. You send electric signals to try to block the pain. The implantable drug delivery systems, we implant reservoirs of opioids, usually opioids, can be something else into the person's body, usually the catheter is going up along the spine, and the medication is being dribbled out in an attempt to block, get rid of the pain. So lots of different things are done, and all the complementary, but a few of them, acupuncture, spinal manipulation, nutraceuticals, et cetera nutraceutical. Oh, and I should go back. And then there are behavioral or psychologically oriented treatments. Cognitive behavior therapies, what CBT is, biofeedback, hypnosis and there's something that became very popular in the 1980s, '90s, call it multi-disciplinary or inter-disciplinary pain rehabilitation programs. These are non-curative. They're rehabilitation. They're not called pain cure programs. They're called pain rehabilitation programs. Okay. So nihlism or reality? How good are these treatments? We've been dealing with pain since at least earliest recorded memory, so you would think by now we're doing really good, okay. So pharmacological treatments. By the way, all these are cited. So if you want the references for these, despite the variety of pharmacological agents, effective pain relief with conventional medical management is achieved in less than half of patients with chronic pain. 16 And that's usually about 30 percent improvement. That's about what opioids, nonsteroidals, anti-convulsants, antidepressants, some of the other common treatments that are used for drug treatments. About 50 percent of people get about a 30 percent benefit. 30 percent it's what's decided by some learn people to be a clinically meaningful improvement. >>: What does it mean, 30 percent? >> Dennis Turk: >>: On a zero to ten scale, if you say your pain is -- Self-report? >> Dennis Turk: Your self-report scale, there will be a 30 percent -- if you look at any of the drug literature, that's the way that they're reported is percentage of your pain that's reduced. Surgical intervention, so maybe they're really good. Pain and function, by the way, in 30 percent and 17 percent are pain-free after spinal fusion, which is the most common type of surgery for back pain. Neuroaugmentive, meaning nerve blocks, steroids, facet joint injection, epidural steroids, trigger point injections, all kinds of other injections have not clearly shown to be effective and can consequently not be recommended, and that's a cited from these different citations down there. None of what I'm showing you is single studies. They're all review papers, meta analysis on and Cochrane collaboration, which is a not-for-profit group that goes out from England and actually develops, evaluates the available research so that's where these are coming from, in case you're wondering. Physical modalities, transcutaneous electrical nerve stimulation. I won't go into the details. Ultrasound. The net benefit for any of these different physical modalities is unclear and the evidence that is available is poor. >>: Is the 30 percent increase 30 percent more than [indiscernible] decreased it, or is that just 30 percent? >> Dennis Turk: I'm glad you asked me that question. It depends, first of all, on whether you're talking about an inactive placebo or an active placebo. An inactive placebo has no side effects. An active placebo mimics the side 17 effects of the true drug. If you look at the inactive placebos, compared to opioids, the reduction pie inactive placebos is about 10 to 12 percent. So you've got 30 percent versus 10 to 12 percent. If you use an active placebo, the active placebo is about 22 percent. So now you're 22 percent to 30 percent. So there's a big difference, and for those of us that work in this world and read that literature, you have to be very careful to what the placebo condition was, because the inactive placebo, if I'm a pharmaceutical company, I want to demonstrate my product is more effective than placebo, I'm going to use an inactive placebo, okay? And almost all the studies are inactive placebos. So that's the placebo rate. Somewhere between -- and it will depend on the study by study, but somewhere between 12 and 20 percent placebo response. 30 to 35 percent for the -- for on opioid. It's about the same for nonsteroidals, for anti-convulsants. >>: What does that mean, an active placebo, like for an opioid? it -- Does it mean >> Dennis Turk: It means I give you diphenhydramine, which will give you dry mouth and some of the dizziness, which is comparable to the side effects you'll see with an opioid. That's what I mean. Active, it tries to mimic some of the side effects of the specific drug you're taking. >>: This is so fascinating. So if you give the passive placebo but tell the people that they might have these side effects ->> Dennis Turk: I could talk for a long time on a lot of different topics, and that's a very interesting one. The patient expectation is extremely important on these things. So therefore, if you're in a study, you have to fill out a consent form. And that consent form, it starts describing all the side effects and all the possibilities. You will see that the side effects people have will mimic the side effects of the active treatment, and they won't come up with side effects that weren't mentioned in there. So there's obviously something that goes on. For those of you that ever watch television, I'm sure none of you ever do, but there's something called direct to consumer marketing. You see drug companies are trying to tell you products. And they list all the possible side effects as fast as they can possibly talk, faster than me. What they're trying to do, by the way, they're trying to 18 legally protect themselves. But they're telling you everything. Now what do you think happens to a patient when he or she hears about that stuff? They start having some of the side effects. So there's called no-cebo, which is the opposite of placebo, which is a negative effect of taking an active drug. That's another story. We can go off on that if you want to talk some other time. Exercise. Maybe if you just gave people the right physical exercises that would take care of all the problems, right? Well, if the criteria for clinically meaningful difference is 30 percent for pain and 20 percent for function, none of the published randomized control trials would have a difference between a treatment and a control group. Not one. If that's your criteria of success. Now, if you use statistical significance, whether it's a statistically significant benefit, we can get a statistically significant benefit, but that's not the same thing as saying what change you have. And to give you just a little humor on the aside, if you want, in most clinical trials, the entry criteria to be in a criminal trial for pain is your pain must be at least a four on a zero to ten scale. Zero is no pain, ten is the worst pain you can imagine, worst pain possible. The reason for the four is that's the cut-off between mild and moderate. If you look at the percentage of patients after the study who are now pain below four, it's a very small percent, which means that even though the drug was successful, you'd be eligible for the next study because your pain was still above four. So therefore, the successful treatment wasn't so successful. Complementary, spinal manipulation, I won't read these to you, but bottom line is they fail. Chiropractic manipulations, other kind of spinal manipulation, I'm sorry if I'm offending anybody. I'm just citing the data. The data isn't very good, and it's not good for all kinds of things. Back pain, headaches, neck pain, carpal tunnel syndrome, dysmenorrhea, lateral epicondylitis, pain in your arm here, musculoskeletal pain, nonspinal pain. Doesn't help. Especially in the long-term. Yes, ma'am? >>: Being someone who's had lots of physical therapy that's always helped a lot. 19 >> Dennis Turk: That's the trouble [indiscernible]. >>: What I get told a lot by the physical therapist is that most people don't go and do the exercises the way you do. So I will always religiously do them every day after I leave the ->> Dennis Turk: You are a compliant or adherent person, and we will talk a lot about that, because that's one of the major concerns is that when people are asked to do things for long periods of time, they tend to drift and not continue. Since we don't cure people, you have to do these forever. And you have to do them forever if you've had a chronic problem. I don't know what the condition was, but if it was following a sports injury, you don't have to do it forever. But if it was following a car accident, you're probably going to be doing it forever. So yes, you have to be compliant. And exercise can work. And exercise, by the way, is a generic term. There are 50 different schools of thought about what kinds of exercises you should be doing. No evidence that any one is any better than the other. Acupuncture, maybe that's the solution. improvement. Little to no clinically significant Uh-oh. Drugs don't work. Surgery doesn't work, exercise doesn't work, complementary approaches don't. Spinal surgery, nerve blocks don't work. Acupuncture doesn't work. What do we do? 30 million people. What are you going to do with them? I'm sorry, 30 percent of the population, a hundred million people. Well, recent studies document over the last decade, 529 percent increase in Medicare expenditures for epidural steroids, which don't work. 423 percent increase in opioids for back pain. 307 percent increase in lumbar MRIs. 220 percent increase in spinal fusions, which don't work. They work for -- they don't work for pain. They work for spinal deformities. If a patient has a spinal deformity then, in fact, that's an appropriate treatment, but it's probably not an appropriate treatment. And if you live in the state of Washington and you're on one side of the mountain to the other, 20 the likelihood of your having spinal fusion surgery goes up tenfold for the same condition. How should pain be treated? Well, according to Cochrane review, and Cochrane is this group from England, U.K., that brings together all this information and tries to be a non-biased presentation. They said that cognitive or psychological interventions combined with exercise, so it's a combination, is what should be used for chronic pain. And fusion may be considered only in carefully selected patients after active rehabilitation. Not before. And I'm going to show you that most of the time, the surgery comes before the rehabilitation instead of the other way around. And it's got to be at least two years. So what you should be doing is a combination of some behavioral health and exercise. That's probably the most effective treatment for back pain. Common features of what is cognitive behavior. I said cognitive behavioral. And what they tend to do are the following. I'll show them quickly so you can see what they are. Those are the characteristics of what these treatments are. Importantly, they try to change the patient's view of him or herself from having a condition that's uncontrollable. People who have a chronic pain, any chronic disease, feel out of control. They can't do anything. Since we don't have a cure, you'd better learn how to do something, and these programs try to teach you. They foster optimism and try to deal with demoralization, encourage patients to attribute success to their own efforts. They teach certain skills. They emphasize active patient responsibility. This is really an important one. It's the active patient involvement. It is not what the physical therapist does to the patient. You doing the exercise is what helped you. It wasn't the physical therapist doing massage. And you've got to individualize some aspects of this. And cognitive behavioral treatments, so they're pretty effective, relatively. And cognitive behavioral treatments have modest benefits. Long over short-term, long-term effect are not known because there are no long-term studies. And they're usually, these behavioral health treatments are usually incorporated within rehabilitation programs and not usually done by themselves, instead of physical therapy, instead of medication. They're done in combination with. 21 Okay. And MPRP is multi-pain rehabilitation programs, and what are they? They just have a lot of stuff. I don't want to go through them. They involve PT, psychologist, all kinds of different physicians, lots of physical conditioning, et cetera. So that's sort of what they do, but notice it's not a cure. It's rehabilitation. Often trying to stop the opioids, which is another lecture I could give you about opioids. Opioids, in the long-term, may have bad consequences, and I don't mean abuse and misuse. I mean physiological bad effects. So we need responds? percentage people did to give attention to who's the responders to these treatments. Who One of the troubles with all of the slides I showed you about the of pain reduction is the average, but the average means that some really well. And we haven't got a clue as to who they are. So when you talked about physical therapy, we know you're a responder. What do we know about you? Well, that's what whole bunch of other things. But what about the people who didn't respond? We don't know. Right now, we don't know who gets what treatment. Right now, whatever treatment you get, it's the hammer in the nail. Wherever you go, whatever their preferred treatment is, you're getting it. And maybe it works very well for 30 percent. percent get minimal benefit. Miserably for 30 percent and 40 Long term follow-ups, we don't really know. There aren't long-term studies. In the pharmaceutical industry, the long-term studies are three months. So put people on chronic medication for the rest of their lives and it's based on research that took place in three months. What happens over time? We have no clue what happens to these. Why three months? Because that's what the FDA requires for a drug to get approved. So therefore, the drug companies are going to do whatever they need to do to get a drug approved because it stands to make them billions of dollars. We have long-term -- there's a few long-term follow-ups. Maintenance is a major problem. Generalization beyond the clinic is a major problem. We bring people into a clinic, and then we send them home. And we didn't cure them, so what happens at home? They relapse. 22 >>: Does this characterizing responders, is this a direction that people are heading, or are you saying this is something people should be doing. >> Dennis Turk: Some of us are doing it. Some of us at NIH fund grants for us to do it, but not everybody is doing it. The pharmaceutical industry doesn't want to do that, because they want 100 percent of the market. So if they find out it works for 30 percent of the patients, you mean we're only going to be able to use our drug for 30 percent of the people. We want to use it for 100 percent. So they don't want to know. So that's partially the problem. But NIH has been funding a number of studies, and there is -- I don't know. It's starting to be more and more people are talking about this is stupid what we're doing. We're giving people generic treatments, and we need to find out more about it. And if I come back, I'll give you another lecture on how we're trying subdivide patient. >>: That's kind of parallel to things you could think of and see in cancer, for example, where chemotherapy responders and not responders is coming down to the peculiar genetic malformation that was responding to that particular patient's cancer. >> Dennis Turk: One way to subdivide patients is based on genetic factors. One may be based on physical pathology factors. You could subdivide them on a whole range of different possibilities. Again that's another lecture that I could give you. But people are looking for that. >>: Right, what makes a responder? A responder is -- >> Dennis Turk: It's unknown at this point what they are, and it's not for some of us not trying to identify. As I said, if I had more time, I could give you a lecture on some of the research that's out there. >>: What makes people who have anomalies and don't experience pain. makes them -- What >> Dennis Turk: Thank you. If you want to write a letter to NIH to support the grants that I write, I'd be more than happy to use that letter, because I've been submitting those grants. And they've been getting funded so I can't complain too much. 23 >>: That's okay. >> Dennis Turk: Okay. That is exactly the future of what we have to be doing. But don't think it's going to happen in the pharmaceutical world, because there's no incentive. So it has to happen through somebody else funding the research. And trust me, the pharmaceutical industry does not really underfund research on exercise. They're not going to fund research on spinal cord stimulators unless they're device manufacturer. They're going to fund research on drugs. So that's why you see a lot of attention given to drugs and much less given to any other type of treatment that's out there. But another lecture. >>: Not a good business model. >> Dennis Turk: It's not a good business -- and poor physical therapists, they don't have a whole lot of people out there rushing to support and pay for their research to demonstrate that they're doing something beneficial to help you out. So we're not curers. We're not going to eliminate pain in all the patients. And we should not be naive to assume that these major life style changes are going to last for long periods of time. Just to give you an idea, these are people who go to rehabilitation programs. These are characteristics. Notice the duration of their pain. 85 months. So that means they've been living with it for a long time. And they've all had surgery before so instead of -- it's the opposite of what their recommendation is. Their recommendation is have the surgery only after rehabilitation. It's the converse. They're having surgery first, and then they go for rehabilitation. I'm going to pass these things. And are these treatment programs, rehab programs any good? Standard care, pain rehabilitation, opioids, antidepressant or anti-convulsant medication, which are two other classes of drugs that are used for pain and spinal cord stimulators, this is pain reduction and this is what you would expect. This strange one over here, spinal cord stimulaters. In very select patients, that's a small numbers of highly selected patients if, in fact, we put these in dwelling catheters along the spine, 30,000 to 50 thousand dollars per patient per five years, and it has to be redone. So it's a very expensive procedure. 24 >>: I didn't understand the rehabilitation thing and the cognitive behavioral. >> Dennis Turk: Cognitive behavioral therapy is -- doesn't include exercise, doesn't include medication, doesn't include physician education or information. It's just focusing on patients learning self-management skills. That approach is often embedded within rehabilitation programs where they get physical therapy, medication management, information from physicians, exercise and that. So it becomes a component. I'm sorry, I'm rushing because I'm seeing my time is not going well. By the way, although statistically significant, pain is not eliminated. Notice pain gone. Very, very, very few people. It's good to feel better, but it's better to feel good. So these people feel better, but they don't really feel very good, because imagine the worst pain you've ever had. You're going to have it 24 hours a day, 365 days a year, for 7 to 20 to 30 years. And I can reduce it by 30 percent. You'd be happy to get the 30 percent, but you've still got a lot of problem, which is why I'm so interested in the kind of things you do and I'm going to get past this. So let's remember the person that's between these symptoms, between the pathology and the symptoms, and this is where that individual difference is that you're talking about starts coming in. This is common and this may be common, but what's different is who's in there. And pain affects all aspects of people's lives. I don't have to tell you that. This is just showing you, as pain goes up, what happens to how it interferes with your life. So, for example, on a zero to ten scale, if you rate your pain a three, you will also say that their enjoyment in life goes down. If you say your pain is a four, enjoyment goes down, and it affects your ability to work and goes up. As pain goes up, things are more impacted. So by the time you get here, if you rate your pain as an eight or a patient rates their pain an eight, it's affecting their enjoyment of life, their work, their mood, their activities, their ability to sleep, their ability to walk, and interact with people. So it's a big problem. And I'm going to have to do this quick because of time. I just want to remind you of the average person who comes to a pain clinic has had their pain for seven years. Their average age is 44. So that means their pain began when 25 they were 37. So by the time that I see them, rehabilitation sees them, they've had seven years to have to live with their pain. And don't forget that people have histories, genetics, anatomy, physiology and learning history. They had 37 years to get to be the person they were before their pain developed. Does that matter? Do you think any of this influences how people adjust, adapt, respond to their pain? And we're going have people live for a longer period of time and they have different resources, and all this happens in a social context. People don't live alone. Social context are family members, next door neighbors, other relatives, what have you. Doctors, nurses. So this is what it's like. So even though I might see them cross-sectionally here, if I forget all of this, I'm going to not be very successful with that patient. And if I saw them even farther, I have to understand that since I'm not curing them, they're going to be going this way. So what am I going to be doing for them here? I'm going to get rid of this stuff because of time. I want to show you about depression, but you don't need to see that. So self-management. Main health and wellness dates back to at least the 18th century. John Wesley, for any of you at methodist or know about methodist, John Wesley was the founder of methodism. He actually was talking about self-management for health back in 1647. So it's not a new concept. Forget the cartoon because of time. So what do these have in common, smoking cessation substance abuse treatment, weight loss, new year's resolution, diabetes care, stroke rehabilitation, management of chronic pain. When do they have in common? They're all chronic. They involve self-management. New Year's resolutions. What happens to most New Year's resolutions? They fail very soon. What happens to weight loss programs, substance abuse programs, diabetes care, et cetera? It doesn't get maintained. Requires long-term maintenance or else it doesn't have any beneficial effect. There's poor adherence to them. High relapse rates, poor maintenance of any initial beneficial effects. And here's a typical pre/post, short-term follow up, long-term follow up. The patient starts with their symptoms, whatever they are, I assume it's pain up here. By the end of the treatment, it would be nice if they came down this low. What happens is the starts relapsing and then it 26 goes back. Because we didn't cure them. So what can you do, if this is a good benefit a good outcome, how can you make the curve go like that, versus like that? Well, Niels Bohr, predictions are difficult, especially about the future. Some of you know Neils Bohr. And if, in factors we're going to start switching now from just the pain to what could we do about the problem, and I'm running out of time so I better talk even faster, well, for consideration of a successful intervention, meaning something successful beyond what we're doing, and here I'm thinking about technological, we've got to think of clinical consideration, technical considerations, and acceptance by the clinician, the patient, the payer, and policymakers. So let's assume we could develop some new intervention. We'd have to be able to make sure it took care of these kinds of things. You have to deal with all the technological -- this is where you guys are the experts. And we'd have to find a way to make these people accept it. So some considerations. And these are not independent, and this is where I'm going to start getting into deep water. So if you start hearing me mumbling and bumbling, you'll know why. Clinical considerations. Well, here's easy. But we do have to worry about who is the population. Is it for everybody? Do we have to worry about are there specific physical limitations, specific symptoms? Would the treatment to be different? So let's assume we're going to develop some technological approach to help people do some type of exercise. Does everybody get the same one? Do the symptoms matter? Do limitations matter? How about the variables and demographics, learning style, computer skills and experience, fears of being abandoned that if you use this technology, I won't see the physical therapist. No support. Sensory or cognitive limits. That means what happens if they have visual or hearing problems. Therefore if you're going to start thinking about developing some type of technological applications, you're going to have to take into consideration this variability. Treatment content, you're going to start tailoring it. Are different people going to get different content? Should everybody get the same thing, or do we use machine learning and artificial intelligence to learn about people and 27 start modifying, customizing the treatment. What's the dose? How much do they need? Is more always better? And I'm going to suggest to you not always. And what's the timing? When does this occur? Is it early in rehabilitation? Is it late in rehabilitation? Would it be different if you got people in the seven or eight months after their pain began than if you got them seven years? Would that differ? What about usability, engagement, connectedness. Can you get the person to engage in this activity. We've been talking or I've been talking about Ran about using Kinect. How do you keep people engaged in something like that. How do you keep them going. If the we want them to do this not for three weeks or four weeks, but we want them to do this for seven, ten, 20 years, what are you going to do to make that specific? How are you going to motivate them, encourage maintenance and generalization? I think you have tremendous opportunities to use the technologies that you guys are good at to help us, because we, health providers, are miserable at doing this. What about monitoring? We've got to worry about the clinician and the patient, monitoring what's going on, feedback that they're getting. How about flare-ups? What should happen if a patient has a good day or a bad day? What about deterioration? What happens if the patient starts doing well and then starts getting worse? What should they do? Who's going to be responsible for that person? Is the clinician still involved? What about red flags? If you see something bad happening, what should happen? Are there parameters? Are there cut points? Are there decision points about if, in fact, certain things happen, you stop doing that. What about feedback. Should you give confirmatory feedback, corrective feedback, diagnostic feedback, explanatory, prescriptive, elaborative? How do you give people information? So they've done an activity, they've engaged in it. Now you want to tell them, you did well, you did wrong. You varied in some way. That's useful for us to know, but it means you're doing something different. How are you going to use that information? So you're going to have to program that in some way to try to decide what kind of feedback are you going to give people. So that's what the clinician is thinking about, how much clinician time can these be free standing or do you have to have clinicians 28 involved in some way, shape or form and how much contact does the clinician have with the patient? So if somebody's gone through a three-week rehabilitation program and now they're going to go home, can they go home for the next seven, 20 years, or do they need to come back periodically? So those are some clinical considerations. For you guys, and here's where I'm in really deep water, you need to be able to personalize the needs and desires of the patients and how do you query these patients and how do you learn about them and test them? And what I mean by the needs and desires, if you develop a very nice excess program that is of little interest to the person you're trying to get to use it, if I have a 75-year-old woman, I'll use that, who is very interested in learning how to be -- has had some type of arthritis, would like to improve her sewing activities, and you think that a good activity is to do something with her hands, and you have a little game in which she gets to follow the fish around like this, how long do you think she's going to be interested in doing that? Unless you find some way to get her to buy in, that this is going to be leading toward what she wants to do, and I think that's going to be a challenge that you're going to have to -- or you should focus on. Format, platform, organization, multimedia, you're going to using text, audio, graphics, pictorial, video. Is it live, is it animated? Those are the kind of things you want to build into this. Pattern recognition is going to be particularly important as you're making decisions about when to modify criteria that you want. Is the patient in or out of bounds or range. Do you want learning and automated adaptation to maintain your engagement? Can you design in such a way that other time, it starts doing things differently and leading to different kinds of innovations that will keep the people engaged. You're getting them closer to things you want to do. You're switching to other activities. So you're going to deal -- you're going to interact with your clinician friends who want to tell you, here's the skills, here's the exercises we need these people to do, and your job is to say okay, how do I take what they need to do and put that into a gaming format that they can, in fact, use and expand over time and also build in the patient's interests to make it relevant for them. 29 Dynamic tailoring to match the clinical needs to the patient's interests. I just said that. Intelligent and conditional prompts. When do you prompt, how do you prompt, what do you say? Again, this is going back to the feedback. Integration of feedback, guidance, reinforcement and finally, what's the frequency and appropriate use of these kinds of things. How are you using this kind of feedback? And then for the acceptance standpoint, is it clinically effective? You have to convince the clinician who you want to use this that, in fact, this is useful. And you have to also be a little bit careful you're not displacing them. Oh, we're going to put all the physical therapists out of business? They don't want to hear that. What they want to hear is that they're still needed. What's the patient's engagement and satisfaction. From the payer, is it cost effective? Doesn't it have to be -- it doesn't have to be perfect. It only has to be worthwhile. So if they can save money on this, even if it's not perfect, it's cheaper, accomplishing even partially what you're going to accomplish with the face-to-face. It may be worth their effort to do it. And you need to be able to look at it. Policymakers are worried about service demand, utility, variability, efficiency, resource sharing, and burden. I could go on to all of these, and I'm assuming you're familiar with some of these concepts. And then chronic pain, why is there an opportunity for you? And there are technological solutions. It's huge in growing population. A lot of people. They're not going away. No significant advance in treatment. So self-care and self-control is going to continue to be essential for a long time. So you've got a lot of people who need to be doing things over long periods of time and we don't have ways right now. We, the health providers, don't have ways of doing it. There's wide variability in response to the existing treatments, and we need to look at the responder analysis and customization of treatment. Can we find out different characteristics of people and then can we customize the treatment whether you do this through artificial intelligence or whether you do it through machine learning. These may be equivalent terms or have unique meanings, but you understand you're learning about the person. And you're modifying things so that not everybody gets the same thing. It may be at base 30 you start the same point, and then as you learn about the person, you start modifying it. Maintenance enhancement benefits over time, using ought made mated knowledge-based reasoning, strategy matching, motivation for different prompts. And this is an important one. This empathy concept, because one of the things that they've done some focus groups on patients using gaming devices about what would be useful and helpful to them, and what they're worried about, and what they're mostly worried about is lack of support. If they're face-to-face with a therapist or if they're in a group of other people receiving therapy, they're getting support. What happens if I'm at home and I did some consulting in New Zealand a long time ago and we had a rehabilitation program and they were sending people back to their homes, and the last day of an inpatient treatment, I ran the group and we had 12 patients, and they sat around. I said Mary, what do you think it's going to be like when you go home? And Mary started crying. So they'd been there for three weeks. I'm there the last day. They brought me from the United States to make the patient cry. So I finally calmed her down. We asked her what's going on. She said I just hadn't started thinking about that. I live on a farm. It's cold and it's damp and I have two little kids. My husband's on a tractor all day. What do I do? And no attempt had been made to say how are we going to transfer this to the Mary's existence. Opportunities. More individualization. You guys can do this. I don't want to go through all these details because of time. It's in, by the way, the handout. The symptoms are going to persist. There will be flare-ups. Going to monitor these things so you can potentially have all types of ways to provide useful information. And that information from some demonstration I've seen, can give reports back to the clinician, who can be monitoring from a distance and make decisions along the way and you can interact with them. Identification of slips and intervene. When is somebody getting out of range. You can develop different parameters, different rules, govern behaviors about when you decide to intervene. Now, be careful, some challenges of methodolatry and technophilia. These are dread diseases for people in your field. You get so caught up with the beauty 31 and the lovely things you can do, the technology, but you got to make sure that that meets with the clinical needs of the patients. Got to make sure that the clinicians are interacting with you as you're evolving those. It's very exciting to see some of the things you guys can do. Then the next question is, can that be translated into a clinical context that's useful. The gee whiz factor is gee whiz, but it's got to have some practical use. Optimize the treatment, and individualize and customize so those are some challenges for you. And determine optimal dosage. I'm not going to go over those. There's more. This we've talked about. Because of time, I'm going to get out of those. I'm going to get to basically what you're trying to do is this. You're going to have to find some way to balance the clinical needs of security, support, discipline, low tech skills that some people may have and how are you going to match that to what happens at home. In the clinic, these things are well controlled. If they're doing these things at home, what are you going to do and how are you going to deal with fatigue, the advantages -- you have to deal with the advantage of flexibility, convenience and availability, but you don't have -- so how are you going to balance those things in the future? And demonstrate successful intervention, depend on systematic and programatic research and we just put it all down there. These are the kind of studies -- I hate to scare you -- that you're going to need to do to be able to demonstrate that your device, your treatment is going to be beneficial if, in fact, you want them to be adopted by anybody out there. Adopted means you want the clinicians to -- I'm making an assumption that all of you care about the things you develop being an I applied and being used out there to make a change in people's lives. And if you don't think that, then you came to the wrong talk. So I'm assuming that about you. In, in fact, you want to do that you're going to have to have the patients accept it. You're going to match things to them. The clinicians have to accept it. The payers have to be willing to pay for it, and the decision maker is going to have to make these things available. And to convince them, you're going to have to do these kinds of things. So what I tried to do, and unfortunately way too much information, all too 32 quickly, pain's a big problem. We don't have a cure. Treatments that we have, have to be maintained over long periods of time. We, the healthcare providers, do not have good ways of keeping these people involved and engaged in the treatment. You have the technological knowledge and abilities to address the concerns in the questions that we have and to make these things real. But the only way it's going to happen is if we do some interacting. So it's been a pleasure to have the opportunity to come out and talk to you about this. And I do apologize for the speed, because I planned too much, which is normally my problem. I don't talk too much, just a lot. >>: Thanks a lot. Any questions? Your slide said life expectancy of 76 years. >> Dennis Turk: There was a plus. >>: I presume that's [indiscernible] is that an approximation of life expectancy at age 44? >> Dennis Turk: Actually, yes. That wasn't -- it was 76-plus, and the reason for the plus, it's getting longer. If you get past the first six months of life, you will potentially live longer. In the United States right now, I believe the age is, if you get past the first five years, is somewhere about in the neighborhood of 82 to 84, and it's different for males or females. So that's assuming that you've got -- you made it to age 44. You got a good chance you're going to live -- depending upon medical problem that are going to develop, car crashes and what have you. But if we don't have that, yeah, you're okay. You and I are okay. >>: I want to get back to this question again of different patients who will respond differently and is there a way to identify which ones will respond well, won't respond well. So we're used to dealing with data, right? So if we have the data of, you know, every treatment applied to every person, whether it worked or not, this has sort of become trivial -- trivial is probably too strong. But it would probably become really easy to identify some patterns about which people are responding well. I assume that data is not available. 33 So what's standing in the way of ->> Dennis Turk: Well, what stands in the way is we have to decide since you can't have an infinite number of variables, because you have an infinite number of subjects that we would need, you would have to say, what are the potential predictors that could be important. Genetic factors, demographic factors, physical factors, learning history factors, support factors. Okay, that's big classes. Within those, there's a huge number of variables. So what's holding back -- I wouldn't say holding back, but where the research is going is trying to identify what's the best predictor. So assuming that I had a sample of a thousand patients and I said that 30 percent of these people responded to treatment X, whatever treatment X was, I could then say can I look at the information I have and predict who those people are. That's the beginning point. The next point would be, okay, now what I have to do is say okay, can I give the treatments uniquely to that group and will they do better, because we can always find predictors, but it's got to make a difference. So that's the research that we're trying to do. That's the research that a number of people are trying to do. The trouble is that there's a lot of -- I just use the word demographic. There's a huge amount of potential -- it's age, sex, pain history, work history, social. You can go on. That's just demographics. The same thing would apply to all the categories. Genetics, which sounds wonderful. Remember when we had the human genome and it was going to solve everybody's problem? Have you seen any recent treatments developed? No. It's going to be a long time, because it's not simple. It's not one gene. >>: A lot of those characteristics, like age, whatever, are in the patient record already, right? So if you had a lot of, I don't know if one hospital is enough data or a lot of hospitals. But it's in there. So you're saying the hard part is this follow-up pass where okay, you found some potential predictors, now you want to do the clinical trials. >> Dennis Turk: predictor side. And you have to do a clinical trial. First of all, even the Let's take the predictor side. If it was just looking at 34 demographics, hospitals collect that information routinely. at demographics. So we could look But let's assume I thought, well, maybe patients' levels of depression were important predictors of who responded. Those are not standardly captured. So that means -- let's assume there's ten or X number of those out there. That means you would have to get different facilities willing to administer questionnaires or do clinical interviews. Very costly. Then you have patient burden; that is, how many questions, how much can we ask people to do? So there are a lot of -- it sounds nice, yeah. We have -- the V.A. system is the largest medical system in the United States. They have wonderful medical records so they ought to be answer these questions. They can on demographic, but as my friend who works in the V.A. said, you've seen one V.A., you've seen one V.A., because they're all different in how they actually do things. Even though they're supposed to be collecting things in the same way, it would be nice if it was as simple as I wish it was. But even on the demographics, it's not so simple. Then there's all these other variables that we don't even -- we don't even know what we don't know. So I said physical pathology or physical functioning. Gait analysis. We think gait is important in predicting who responds to treatment. As we were talking, how many parameters are there potentially available to try to analyze gait so that you have to put all those in there. Every time you increase one of those predictors -- I'll use a crude rule of thumb. How many, what, 10-to-1, 100-to-1? Ten patients to every one variable you would put. So imagine you've got a hundred variables. You could see what happens. And then that only identifies a predictor. Than you have to do a clinical trial. When you do a responder analysis clinical trial, like on the power calculation, how many subjects do you need to do this study escalates dramatically. >>: You've been doing this for a long time, though, so if you were making kind of an intuitive guess, and you must have made a million of them. >> Dennis Turk: are. I have. I know. I know the truth. I know who the responders 35 >>: Do you know the truth? >> Dennis Turk: >>: I know the truth, with a capital T. I've been looking for it for a long time. >> Dennis Turk: Let me give you one bit of information. We have a 61-item questionnaire that asks people about the impact -- how many pain they have, impact on their life, their ability to function, the activities they engage in, and how much support they get from a significant other and how people respond to them. We did a statistic called a cluster analysis to see if, in fact, you'd find patterns of responses within those -- how patients respond to that 61-item questionnaire. We found three different types of patients. We then looked at three different types of patients to see whether those types differed by physical pathology. No. Do they differ on anything else we could find out about them? No. We looked across different diseases, the same three types. Cancer -metastatic cancer, [indiscernible] cancer, lupus, back pain, headaches, fibromyalgia and one more that I can't think of. We found the same three sub-groups of patients occur. We then did a clinical trial in which we gave all those patients a standard rehabilitation treatment. We found that one of those sub-groups of patients, two-thirds of the patients got significant benefits, one of the other groups, only a third got a significant benefit. So we now know, we could predict who was going to do well with that particular treatment on that one study. So we got one study to show that we can, in fact, identify responders. We can then tailor -- we can give a standard treatment, identify who responded to the treatment. The next step would be to say okay, now that we know these three sub-groups, can we have a specific treatment that's different for each one of those three. That hasn't been done yet. So that's to be -- have me come back, and we will have the answer for you within the next three years. So we know, at least for rehabilitation oriented treatment -- but remember, I showed you drug treatments. 36 >>: I have some curiosity. one cluster group that -- Tell us about that one group. So you found this >> Dennis Turk: Okay. We looked at patients who came to a pain rehabilitation program. So they were all referred. Now the thing you need to be aware of is who gets referred to those programs? They're not the average person on the street who has arthritis in their shoulder. They're the people who are the most difficult to treat. So we're getting a very difficult population. So we're looking at, within that set of people, there are three sub-types. One type we referred to, based on their response, as being, quote, dysfunctional. They have a lot of pain, interfere as lot with their life. They have high levels of mood problems, mood, distress, depression and anxiety. They say they get modest support from people in the environment, and they're very inactive. My first thought and your first thought should have been, well, that's all of them. Aren't they all like that? No. Another third of the patients had those characteristics but what was most unique about them, they said they got no or limited support from people in the environment. People are very negative to them. They don't get encouragement from family members so that the social support system seemed to be very different than that group of people. A third group of people we referred to as being, quote, adaptive copers. They're all coming pain clinics. They're all the worst of the worst. Relative to these other two groups, they were doing better. For the people who were dysfunctional, a lot of pain, a lot of distress, a lot of mood problems, inactive, this rehabilitation program, at least for two-thirds of them, seemed to be pretty good treatment. Pretty good doesn't mean cure, remember. Pretty good means we got 30 to 40 percent benefit, statistically significant. For the people who somewhere inter-personally distressed, less than half of that other group got that kind of benefit. The treatment that we had did nothing about inter-personal problems, did nothing about social support, did nothing about how to communicate with family members. So for that group of people, maybe what we need to do is take some of the part of the other treatment and add on a module that focuses on that. >>: [indiscernible]. >> Dennis Turk: No, no, no, we don't give lobotomies. We don't do that. We 37 stopped that in 1944. Last lobotomy I heard of. They still do ECT, electro convulsive shock therapy for patients. You had a question in the back? >>: Yes, I was watching from downstairs. So I wanted to ask you about the [indiscernible] technological involvement and serving tools that exist in that space. So some of us use crowd sourcing tools like Mechanical Turk and a few other sites of that nature. Given that these chronic pain conditions are so common within just any kind of group, is there any experience on using those kinds of [indiscernible] tactics to assess the effectiveness of anything, or do you actually have to go to much more [indiscernible]. >> Dennis Turk: In my experience, in my reading literature, very little effort has been done to use that, except for one minor area. People are interested in misusing opioids have used crowd sourcing techniques to go in to try to learn about those groups. But as a general rule, it has not been a technology -- I haven't seen anything that's used -- I'm embarrassed to say that 99 percent of the things that you guys can do, I don't see it being used very well in the healthcare world, in the rehabilitation world. Not just pain. I would say the same thing about the way if we were talking about diabetic patients. People with diabetes don't get cured by our treatments for diabetes. Their symptoms get normalized, which means that they've got to continue to watch their diet. They've got to test their urine or their blood. They've got to watch their exercise problems, they've got to be careful about infections. They've got to worry about travelling in time zones and changes. That means self-responsibility, self-management for any chronic disease. And I don't think, to my knowledge -- we are so far behind what you have the opportunity and the tools available to help us with that we have essentially lost out on all the things that you guys are doing. I'm delighted that there was any interest in me even coming to talk to you because if, in fact, I could get any of you interested in doing that, you potentially could have -- that's why I was trying to hit you with the numbers. A lot of people, it's very expensive. It's getting worse. So there's an opportunity here, and to the extent that you can use any of the technologies that you have, there's really virgin territory. It's just all -everything you want to do needs to be done, and hasn't been. That's good news and bad news. The good news is you've got a lot of opportunity. The bad news is you've got to do a lot of stuff. Yes, sir? 38 >>: This is a random idea. Have you come across [indiscernible]? name ring a bell? Look him up. He can ->> Dennis Turk: >>: Spell his last name. V-o-n-a-h-n. >> Dennis Turk: Does the Two words. Okay. >>: He set up a game to make people identify pictures on the web and he had to shut down his website because oversubscribed, and I think he sold it Google. >> Dennis Turk: What I would want to do is take that knowledge in finding a way to craft it so that it becomes appropriate for the kind of things -- again, I did it fast, but I showed you all the individual variation things that a clinical person is going to be concerned about that's different from if you just go to people on the web in general. So I think there's going to have to -- get out of the silos, you know. We're over here doing it at the University of Washington, department of medicine or healthcare and you're offer here in Microsoft Research. And if we don't talk to each other, if we don't learn about the things that you're being able to do, and if you don't see the kinds of concerns and problems we're having, we're going to keep going parallel. We're not going to get to it. So thank you for having us come out. We greatly appreciate it. So thank you for that bit of information and the question is going to be how do you take that technology and craft it so that it can be used for these populations. So good for you. I hope I answered your question. >>: So you mentioned clustering populations, you mentioned trying to predict effectiveness. This is sort of getting into an area a lot of us are familiar with in machine learning. So this is a question for you. The clustering approach is beneficial because you can see, okay, here's a group of people that it's not effective on and why. What's different between these clusters. So it's very interpretable. Would it be useful if you had something that instead of was very good at predicting, but you have no idea why it predicted this? 39 >> Dennis Turk: >>: I don't care why. High accuracy, this will work well, this will not work well. >> Dennis Turk: I don't care why initially. Show me that something has that ability, then I'll work backwards and try to understand why. Going forward -let's assume I gave a complicated rehabilitation treatment program, which has a lot of components to it. First, I want to see can I make that work. Then I want to see what's necessary and sufficient from that. I want to dismantle it so it's not the psychologist, it's not the physical therapist. It's only what they really need is support from people in the group. Maybe that's all that's really important. First, let's see it works. Then we'll work backwards and try to get those -- and the content and the predictors all that we worked out to be continued. >>: I don't know if I explained very well. What you're saying, well, once we know that it works then you can back up. Instead if I was only able to tell you what you've come up with already, it will work for that person, it won't work for that person, and I can't tell you why is that useful? >> Dennis Turk: It's useful in the short-term, because I could prescribe, okay, people with these characteristics get that treatment. People get that treatment. But I, as a scientist, I want to know what's the mechanism by why that is working. What is there special about -- what's different or special about this person? So I don't want to use demographic, I think, but let's use, over simplify it. People who are more educated do well with this than do well with that. But I want to work backwards to understand what that is. But if tomorrow I was going my office and you said to me I can predict with an 80 percent accuracy that people like this do well with this, and you have good data to support that, let's do it. I mean, let's help the patient, but then I want to start -- the scientific part of me says let me understand that. >>: Okay. 40 >>: I think there is a patient acceptance in that sort of thing. Certainly, if you tell me I'm in this group and I want to give you this treatment, I'm going to really push back on why. And if it's just, you know, well, the machine learning said such and such versus we determined that it's because you have this particular physical attribute, which one's going to make me happier? >> Dennis Turk: What if I said to you, we have two different treatments we could offer you. With one treatment, given what we know about you, you have a 70 percent chance of really getting a benefit that's important to you. If we give you this other treatment, we have about a 30 percent chance. Which one would you prefer? >>: As long as you've got enough to convince whatever -- >> Dennis Turk: I have to convince you. So if we have the data -- if [indiscernible] knows with a certain amount of predictability that the likelihood you're going to benefit, I'm still going to have to be a clinician. I still have to explain it. I would never bring a patient in and say machine said do it. What I'm going to have to say is I've go the to help you get to the point, which is where I've rushed through, kind of things the clinician is thinking about are not necessarily the things you're thinking about but if you work with them, they can start saying, this technology is great. What you've just said is we've got to figure out how are we going to get that into the hands of patient. >>: How do you get the information, and how do you communicate with the patient. >> Dennis Turk: That's my training. That's what I do. My training as a behavioral health psychologist so I know how to do that, and there's good literature to help on that. What I don't have any clue on is how do I take the opportunities that the technology provides to be able to get to the point where I can say to the patient, hey, let's have this conversation. I don't have that conversation. Right now what happens is depending upon what specialty doctor you go to, or where you go to them, you're going to get that treatment because that's what they like. You need biofeedback. I'm recommending it. Now, a discerning patient says wait a second, how do you know? The average 41 patient says the doctor thinks I should have that, maybe I ought to have that. That's when I get. I don't think the average patient is going to be -- when patients go to see a doctor, they are usually at the point of needing somebody, some help and support, and they're happy for somebody to give them guidance and tell them what to do. So it's not -- more information and more choice is not always what people want. If you developed a problem of some type of cancer, and you went to an oncologist and the oncologist said, well, it's up to you, what treatment would you like? I have a hunch that that you would probably say, well, you're the expert, what would you give a family member if you had a family member? And you'd probably be happy to have that, because you're not the expert in oncology. So there's some -- in the same way if I come to you and talk about machine learning, different stuff like that, and you say, well, you should use this approach, I'm not going to say well, no, I don't know if I like that approach. It doesn't sound too good. My Aunt Mary told me that if I use the Wii system, it's better than the Kinect system. I'm not going to do that. I'm going to trust. If a plumber comes to my house, I know nothing about plumbing, plumber says I need something, fix it. Mechanic says I need something, fix it. I know nothing about cars. So if you know nothing about it, you're dependent upon the, quote, expert who came, who knows everything about nothing, to answer your problem. But I think don't lose sight of that clinical interaction is a very different one than if you're selling a product, buying used cars or selling insurance. There's something about a doctor or a healthcare provider patient interaction. There's a power to that interaction, and the acceptance level from the patient of all kinds of horrible things being done to people, we've done terrible things to people. But there's an acceptance of that, because you're trusting that the healthcare person has your best interest at heart. They're more knowledgeable than you are. But sure, I've got to explain it to you. I wouldn't just say shut up, which I used to do, by the way. Come into the doctor. When women were going to have babies, they weren't given choices about what kind of anesthetic or -- they were told, this is what you're getting. There was no choice given to them. 42 That's changed. So you do have some choice, but you do still listen to the provider, to some extent, and balance what they're saying. You're a highly educated person so you may be a little bit more critical. But the average person who goes to the doctor pretty much wants the doctor to tell them what do I need, fix -- help me to get rid of this problem. >>: There is a lot of evidence also showing that having choice is also important. So you want to have, yes, you want to have the experience, but you still want to control. >> Dennis Turk: If the choice is between two treatments that are reasonably comparable, yes. If the choices are between you could have surgery or you could have sulphur mud baths, I don't know ->>: Something that has 70 percent of helping you, but might have this side effect. Versus this has 30 percent but have that side effects. >> Dennis Turk: Some people like choice. Some people get very stressed by having to make that decision, because they would prefer to have an expert tell them so choice is not always -- we have to be very careful of stereotypes of assuming everybody wants. I think there's huge variability in what people want, and I think a good clinician, without realizing it, is actually sort of deciding what information to give and how much to give based on his or her perceptions of you and the kind of questions you're asking and how anxious you're looking. They're paying a lot of attention. And touching you. Believe it or not, physically being touched, from when they surveyed patients about what they did and didn't like about the distant learning kinds of stuff was there's something about somebody touching me and making sure, reassuring me that I'm doing it, that, you know, you can send me a message over the phone or send me a graphic telling me I'm doing fine, but there's something about that clinics. So that's a little bit of -- and I think where the fun's going to be is how can you have some type of monitoring by a clinics periodically going on so the patient feels they're getting some, but it's not all the time that they're constantly be given. And I think that will be creative what we can come up with. 43 Thanks for hanging in there. >> Ran Gilad Bachrach: Thank you very much.