 All right, so we're gonna get going. Thanks everybody for coming to the first portal and HMS Center for Bioethics Health Policy and Bioethics Consortium of the Year. It's great to see such a big turnout for this. We actually ended up getting 142 RSVPs. And so we're gonna be taping it and hopefully people who were not able to fit into the room will be able to catch it later. If you do want to tweet about anything that comes up, the hashtag that we use for this series is hashtag policy ethics. And we wanna also acknowledge the support provided by the Oswald Cayman Fund at Harvard University for this seminar series. So just to give you some background, so my name is Aaron Kessler. I'm a physician and lawyer and I'm the director of Portal. Portal is a research center based at Bring Women's Hospital that's focused on the study of the intersection of law therapeutics and public health. We have three full-time faculty members, five postdocs, one of which is gonna be the moderator today, Mike Sinha. Numerous students who work with us. So if you're interested in any of these topics, please reach out and let me know. You can see here some of the, this is some of the stuff that we do. This is a recent JAMA article on cost savings from using inexpensive generic drugs instead of expensive brand name combination medications. And there's an opinion piece that we wrote in Bloomberg. And we teach courses at the HMS Center for Bioethics, of which this serves as one as well. Here's our website and you can follow us on Twitter as well as sign up for the mailing list so that you can be alerted to subsequent policy ethics consortiums. So just to give you a background, the objectives of this consortium are to articulate key issues in the healthcare system and public health that involve ethically challenging policies or practices. Bring together experts and we've got two fantastic ones today with different perspectives or experiences to consider and propose solutions to these ethical and policy dilemmas. And then to try to stimulate conversation and further academic study of the topic to help advance the field. So these events occur every second Friday of the month during the school year. This is the first one and this is our agenda for the rest of the year. So save the date in October. Larry, Gostin and Vanessa Kerry are gonna be talking about global health security. In November, we're gonna be talking about provider consolidation with Lee Moore Daphne from the business school and Eric Gold from the US Attorney's Office in Boston. And then in December, talking about expensive medical treatments in the context of this drug called Luxterna with Steve Pearson and Jason Commander from NASA in here. And again, if you sign up with portal, you'll get notices of all of these. All right, so I wanna introduce our topic today, the US opioid epidemic. Where do we go from here? First, we're gonna hear from the moderator, Mike Sinha and then we'll hear from our two expert discussants and thank you all very much for joining us. All right, I'm gonna start off with a little introduction on the opioid crisis which at this point is really a public health crisis and is worsening as we speak. These are some of the most recent statistics from NIDA. National overdose deaths reached approximately 72,000 lives in 2017. You see that there are more males than females but they're both certainly on the rise. Overdose deaths involving opioid pain relievers have doubled since 2002 but are climbing at a far slower rate than some other drugs such as heroin. You're seeing a quite a substantial climb, 16,000 lives relating to heroin lost in 2017. And to give you some comparison, other synthetic opioids and predominantly fentanyl and you see here the fentanyl deaths in 2017 are approximately double the number of deaths from heroin and that's rising much more substantially. Another concern is polysubstance overdose. Opioid involvement in cocaine overdose is also climbing significantly. You'll see the yellow line there, cocaine in combination with any opioid and this is often due to illicit preparation of opioids fentanyl with cocaine. You're also seeing a significant rise in benzodiazepines which is likely due to a concomitant prescription of both benzodiazepines and opioids. In Massachusetts, I'm afraid the problem looks even more serious. It looks like we've got an approximate death rate of about three times the national average in the United States. And you can see here on this map that it's worsening over time and it's really affecting most areas of Massachusetts. In response, Governor Charlie Baker proposed his own bill known as the CARE Act. CARE is an acronym standing for C, Combating Addiction. One of his proposals was to introduce a commission to study medication assisted therapy such as methadone, buprenorphine and injectable naltrexone or Vivitrol. Accessing treatment, he sought to increase treatment in jails, prisons and emergency rooms among other things. A goal to reduce prescriptions of opioids across the commonwealth including partial fills for first time opioid prescriptions meaning that someone can be dispensed 10 pills and then if they need more later they can go back to the pharmacy and obtain the remainder of their script. And finally, enhancing prevention, increasing, strengthening the standing order for opioid antagonist including Narcan in pharmacies across the commonwealth. So Governor Baker's proposal had tremendous support from the Massachusetts Medical Society. One proposal in his initial bill that was not passed was a proposal to authorize medical professionals to hold a patient for up to three days for substance use treatment only and this was not included in the compromise. This was something I raised with the Massachusetts Medical Society and passed a resolution at their annual meeting in June. So again, as I said, standing order means you can walk into a pharmacy and obtain naloxone and this is what I did just a few weeks ago right across the Strait of Brigham and Women's Hospital and there's a local organization Western Massachusetts. We are allies, they give you a little package that you can carry along with you on your bag and it prompts you to ask questions. So it's fostering a dialogue about opioid addiction in Massachusetts and nationally. Congress is also on the verge of passing its own bipartisan opioid package. The Senate bill has gone through multiple committees, over 70 senators have contributed to the language. It seeks to increase access to treatment, heighten border control for fentanyl and derivative car fentanyl and increase research on non-opioid pain treatments. But a lot of advocates argue that it doesn't go far enough because it doesn't really pay for expanded addiction treatment. The CBO estimate for the bill is $8 billion over five years. Advocates are saying we need tens of billions of dollars infused to reverse the tide of the opioid crisis now. Other coming things, these are just news clips from the last few months, cost issues. Narcan Maker Adapt Pharma was acquired by Emergent Biosolutions. Who knows what that means for access or price of Narcan moving forward? Oxycontin's manufacturer Purdue Pharma obtained a patent for a drug to treat opioid addiction. As many of you know their drug Oxycontin, perhaps contributed to the rise of the epidemic in the first place. President Trump's opioid plan also focuses heavily on injectable naltrexone or Vivitrol, a very expensive drug for which the costs and benefits are not well established. In addition to access issues. So, New York Times recently ER treating at opioid addiction being very rare. Also in the New York Times, most doctors ill-equipped to deal with the opioid epidemic and few medical schools teaching addiction. And finally, and for the reasons given above, doctors have been slow to adopt medication-assisted therapy for opioid treatment. So with that introduction, I'd like to introduce our speakers. Our first speaker is Dr. Andrew Coladney, Senior Scientist at the Institute of Behavioral Health at the Hellerow School of Brandeis University and Co-Director of the Opioid Policy Research Collaborative. His primary area of focus is on the opioid and heroin crisis, which is devastating families and communities across the country. He is also the Executive Director of Physicians for Responsible Opioid Prescribing, an organization with a mission to reduce morbidity and mortality caused by overprescribing of opioid analgesics. Dr. Coladney previously served as Chief Medical Officer for Phoenix House, a National Non-profit Addiction Treatment Agency, and as Chair of Psychiatry for Maimanides Medical Center in New York City. He began his career working for the New York City Department of Health and Mental Hygiene in the office of the Executive Deputy Commissioner, where he helped develop and implement multiple programs, including citywide buprenorphine programs, naloxone overdose prevention programs, and emergency room screening, brief intervention and referral to treatment, also known as ESPR for drug and alcohol misuse. Dr. Coladney completed his medical training at Temple University in Philadelphia and his residency in New York City at Mount Sinai School of Medicine where he was Chief Resident. He completed a fellowship in Columbia University in New York and his board certified in psychiatry. Our second speaker is Dr. Jesse Gada, who is the Chief Medical Officer of the Boston Healthcare for the Homeless Program, where she has practiced internal medicine since 2002. She oversees the clinical practice of this unique community health center that serves 12,000 people annually across dozens of clinical sites, including homeless shelters, the street, and one of the first medical respite programs in the country. Dually Board certified in internal medicine and addiction medicine. Dr. Gada graduated from the University of Maryland School of Medicine in 1998, trained in internal medicine at Boston University Medical Center and served there as Chief Resident in 2002. She remains affiliated with Boston University School of Medicine as an assistant professor of medicine. She also completed a physician advocacy fellowship at the Columbia University College of Physicians and Surgeons in 2007. Dr. Gada has a long history of advocating for the needs of individuals experiencing homelessness. She has been published and spoken widely on the intersection of homelessness and health, and she directs BHCHP, Boston Healthcare for the Homeless Programs Institute for Research, Quality, and Policy in Homeless Health. She has led their efforts to respond to the opioid overdose crisis, which has been magnified among people experiencing homelessness in Boston. Her passions include ending homelessness and bending the curve on overdose deaths. We'll start with Dr. Colani. So it's a pleasure to have this opportunity to talk with you about the opioid crisis. I know the title for today's seminar is Where Do We Go From Here? And I'm not gonna, in my opening remarks, really answer that question. I'll touch on it briefly. I think we'll be discussing. What I'm gonna really start with though is talking about what the opioid epidemic really is because I don't really think we can talk about where we go from here if we're not really all on the same page about where we are right now and what's actually going on and what is the opioid crisis. The opioid crisis is sometimes described as a drug abuse problem. This is the way the pharmaceutical industry likes to frame the crisis, that this is an issue of people taking dangerous drugs because it feels good. Abusing these dangerous drugs and they're accidentally killing themselves and we've gotta stop that bad behavior. That's the opioid crisis. People trying to get high off of these really good medicines is the way they would frame it. You'll also hear the opioid crisis frame sometimes as really a problem of despair that the real issue is socioeconomic distress and middle class white Americans and that as their plight has gotten worse over a few decades, that they're drugging themselves and drinking themselves and committing suicide and that that's really what the opioid crisis is just a symptom of this broader societal problem. You'll also hear the opioid crisis described really as an overdose death epidemic. Which I think is really a mistake to just really zero in on the overdose deaths in my view that would be like framing the AIDS epidemic as an epidemic of PCP pneumonia. PCP pneumonia was how many people with AIDS were dying but we had an epidemic of people with HIV infection. That's really what the AIDS epidemic was. So I think the correct way to frame our opioid crisis is as an epidemic of opioid addiction. It's an epidemic of opioid addiction meaning that all of these different health and social problems, the soaring increase in overdose deaths, the increase in infants born opioid dependent, the large increase in children entering the foster care system, the soaring increase in deaths involving fentanyl, the impact on the workforce. The driver behind all of these health and social problems that we are really talking about when we talk about the opioid crisis I believe has been a very large increase in the prevalence, the number of Americans suffering from the condition of opioid addiction and that's what's really driving all of these different problems. And I'm gonna show you the opioid addiction epidemic happening over time with a series of maps. So I believe our opioid addiction epidemic began in 1996. This is three years into the epidemic. And on this graph the states that show up as red or maroon are the states that have the highest rate of people showing up at a state licensed drug or alcohol treatment programs saying that the primary drug that they're addicted to is a prescription opioid. So the states with the most serious problems show up as red or maroon. And you could see that three years into the epidemic in 1999 there were a few states lighting up with a pretty serious problem. And I want you to watch what happens to the color of the map as we go forward in time. So this is 99, 2001, 2003, 2005, 2007, and 2009. So by 2009 in every state in the country there had been a very sharp increase in the prevalence, the number of Americans suffering from the condition of opioid addiction. When you have a sharp increase in a disease over a short period of time that is the definition of an epidemic. Now what's caused the maps to turn red like that and what's really caused our opioid addiction epidemic? Let me just move ahead a little bit. Actually I'll get to it in a moment. That's the slide's a little out of order. So I'm gonna explain what's caused the maps to turn red in a moment. But we have three groups of Americans who are opioid addicted. And this is something that really gets lost in the discussion because particularly when we focus in on overdose deaths or the drug involved in an overdose death we're really forgetting that there really isn't a single population of drug users who shift from one drug to another. We have I believe roughly three groups of Americans who are opioid addicted. The first group is a group that's primarily white. They're in their 20s, 30s, early 40s. Their addiction begins with prescription opioids and many of them wind up turning to heroin after becoming addicted to prescription opioids because if you're a young, healthy looking person, even if your addiction began with medical use of pills as opposed to recreational use, it's hard for a healthy looking 25 year olds to get a lot of pills from a doctor on a monthly basis so they wind up on the street where prescription opioids are very expensive and so they switch to heroin. And this is a group that has been transitioning to injection heroin use as well at a very high rate. The second group also affected post 1995, also developing its addiction through use of prescription opioids or middle-aged and up. And this is a group that really doesn't have to switch to heroin after becoming addicted to the pills. It's a group that is able to get pills pretty easily from doctors and many in this group are really developing their opioid addiction through medical use. And then the third group are individuals who really are survivors of the heroin epidemic of the 1970s. They're more likely to be non-white. They're more likely to be male than female. It's mostly these older men. And in the first group and the third group we're seeing overdose deaths soaring because of fentanyl in the heroin supply. And in this third group you have these men who managed to survive despite their heroin addiction. For 40 or 50 years, many of them survived AIDS which killed tens of thousands of injection drug users. They've seen many of their friends die of overdoses over the years. They've made it to their 50s and 60s despite their heroin addiction, probably with periods of abstinence or treatment and then relapses and in this group the deaths are going up very rapidly now because of fentanyl in the heroin supply. So in inner city DC, North Philly, South Bronx and many different parts of the country where you'll find that population, the deaths are going up. Now this is a slide I don't like. It comes from the CDC's website and it's based on sort of a new framework for the opioid crisis which I don't think is very helpful where the opioid crisis is described as happening in sort of these three waves. A prescription opioid wave and then a heroin wave and then a fentanyl wave and the reason you might frame it this way is if you're just looking at the drugs involved in the deaths instead of really understanding that there are different populations affected and if you think of the opioid crisis as really just an overdose death problem, maybe that makes sense but again overdose deaths are really one piece of this problem. There are many other problems associated with an epidemic of opioid addiction aside from the fact that we've got record high overdose deaths. So I don't think this is very helpful. I think that we really do have to think about the opioid crisis in a more complex way. Let me just go back to this also. The explanation for this trend that's very popular, you see the top line which is prescription opioid deaths. You see how it's sort of leveled off at the same time that deaths involving illicit opioids began to take off. The explanation you'll hear for this trend is that the drug users switched. So there was a crack down on the pills so the drug users went from the pills to heroin and that's what's going on. That's what explains these overdose death trends and that's a conclusion you would draw if you're only looking at overdose deaths but that really isn't what's going on at all. The reason we've seen this sharp rise in deaths involving illicit opioids is because the illicit opioid supply became so dangerous with fentanyl and even though you see this lag between heroin and fentanyl which shows up as black, that lag may have more to do with the fact that fentanyl wasn't being tested for regularly when it first emerged and then medical examiners began to test for it. It is not true that there was a sudden shift from prescription opioids to heroin in the context of a so-called crack down. The rise in heroin use, the switching began much earlier. And you see that here on this slide. On the right is non-Hispanic blacks. On the left is whites. And I want you to look at the red line which is the age group 20 to 34 years old and you'll see among young whites in the United States heroin use began rising very rapidly at the beginning of the prescription opioid crisis. These were young people who were switching and if you look as well on that graph if you look at the green line for whites, middle-aged white people, you don't see rising use of heroin. Again, that's a group that is more easily able to get pills from doctors even after they've become addicted. Something that many people don't realize is that when you compare the rate of overdose deaths or the number of overdose deaths that have been occurring in this young white group that switches to heroin when you compare their deaths to the middle-aged and older whites who don't switch to heroin up until the fentanyl emerged, we were seeing many more deaths in the people getting pills from doctors than we were in the young people out there using heroin on the street. And you could see that on this graph. So the light blue are opioid pain reliever deaths, the dark blue is heroin. And you could see significantly more deaths involving prescription opioids than heroin and the age group where we were seeing the most deaths was that middle-aged group. This is an infographic that the New York Times put together and what it's really showing you is this young group now catching up. And the young group has surpassed the older group now that we have this extremely dangerous heroin supply. And you can see over time with fentanyl, many more deaths now occurring in that young white group and in the older non-white group. So this was the slide I meant to talk about previously, what's causing our opioid addiction epidemic? What caused those maps to turn red? And this is a CDC slide. And the CDC has been perfectly clear about what's causing our opioid addiction epidemic. The CDC is showing us here that as the prescribing of opioids, the consumption of prescription opioids began to increase in the United States, which is the green line, that rates of death, which is the red line involving prescription opioids and addiction to prescription opioids, the blue line, that they went up in parallel. The CDC has really been saying that this is an epidemic that's been caused by us, the medical community, that as we started to prescribe opioids much more aggressively as the prescribing went up, rates of addiction and overdose deaths went up right along with the increase in the prescribing. And the CDC's message has been very clear as well. Their message to us is that we may not be able to bring this epidemic under control until the prescribing trends much more cautious, until we really get to the levels of prescribing where we were before we had this epidemic. I can tell you that pharmaceutical companies that manufacture opioids don't agree with the CDC. And initially, up until around 2004, they were actually arguing that this association didn't exist. And scientists who were getting paid by pharmaceutical companies were putting out papers saying that the prescribing is going up, but we see no adverse public health consequences associated with the increase in prescribing. And when it became starting to become clear that there was an association, they were arguing that these are not pills from doctors prescriptions, but they're pills being stolen from pharmacies. And they've now stopped making those arguments. They've now acknowledged the association between the increase in prescribing and these adverse public health consequences. What they're arguing is that the prescribing doesn't have to come down. They're saying that if we make the pills hard to crush for snorting or injecting, if we teach doctors to monitor their patients more closely, we can have our K-Koneta too. The green line can stay high. It can continue to go up, but we can make the red line and blue line go down. And unfortunately, that won't work. And it's not just that the manufacturers are saying these things or they're experts that they pay are saying these things. They're also putting their money where their mouth is. They're spending quite a bit to try and block state and federal interventions that might result in more cautious prescribing. This data comes from an investigation by the Associated Press in the Center for Public Integrity, which found that over the past 10 years, the opioid lobby, the manufacturers and distributors, outspent the gun lobby. They spent eight times more than the gun lobby in their efforts to block regulations that might result in more cautious prescribing. They had spent 880 million over the past 10 years. I mentioned earlier the pharmaceutical industry, frames are opioid crisis as a problem of drug abuse. This is more specifically how they'll frame the problem for policy makers. And this is a slide that was shown at an FDA meeting by the head of a pain org, making the argument that FDA shouldn't put drugs containing hydrocodone like Vicodin, hydrocodone combination products, shouldn't put them into the Schedule 2 category, which is more restrictive. They were, the point of this slide was to argue that FDA, if you put the drug in a more restrictive category so that doctors can't do six months' worth, five refills on a prescription and phone it in easily, if you do that, you're gonna be punishing the pain patient for the bad behavior of these drug abusers. It was framed as if all of the harms were limited to so-called abusers, which of course was never the right way to frame this problem. And millions of people with pain have become opioid addicted, thousands have died of overdoses, and these are lousy drugs for chronic pain. Prescribing has started to come down, fortunately. This is the drop in oxycodone prescribing in the United States, the blue line. And you can see the comparison to oxycodone prescribing per capita in Europe. And despite the drop, we are still not even close to the levels of prescribing in Europe. This is just oxycodone. This is more data showing you all opioids and morphine equivalents, and you do see that the prescribing has started to trend down, but we have a very long way to go before we're at the levels, the pre-1996 levels. There was a federal review. Federal government looked at all of the evidence to support long-term use of opioids for chronic non-cancer pain. This is the review that they published, and the conclusion is highlighted here. They looked at all of the evidence, and the conclusion was we cannot find evidence that putting patients with chronic pain on long-term opioids is helpful. We did find evidence it's dangerous in the higher of the dose. The more dangerous it is. If you think about that for a moment, if you think about any medical intervention where you don't have evidence that that medical intervention is gonna help a patient, but you do have evidence that that medical intervention is dangerous, those are medical interventions that we should prescribe rarely. Opioids are still routinely prescribed, though, for chronic pain. There's been a focus, and we're gonna be talking about this, I think in a moment, a focus on more cautious prescribing for acute pain, states passing, limits on first-time prescriptions. One of the reasons why thinking about more cautious prescribing for acute pain is so important is many of the people who wind up on long-term opioids began not with long-term chronic pain, they've tried everything and a doctor said, okay, let's see if opioids will work for you. Often it begins with an acute pain problem, even post-op or injury, and this was a study published by the CDC. They found that if a, they looked at the initial prescriptions, initial episode of opioid use, they found that if a patient took an opioid every day for 10 days, one in five patients were still on an opioid one year later, and they looked at patients who had taken an opioid every day for 30 days, and if you took an opioid every day for 30 days, 40% of patients were still on an opioid one year later. This doesn't necessarily tell us these people all were addicted, but it certainly speaks to the physiological dependence, that's a serious problem with these drugs. How do we end our opioid addiction epidemic? Well, I think one of the reasons it's really important to frame the problem in the right ways, because if you do frame this as an epidemic of opioid addiction, what we need to do about it becomes much more clear. We have to prevent more people from becoming opioid addicted. More than anything else, the interventions there will be interventions that result in much more cautious prescribing so that we don't directly addict patients, and so that we don't stock homes with a highly addictive drug where family members can become addicted. And then of course we have to see that people who have this disease are receiving effective treatment. These first two bullets are really similar to how you would respond to any disease epidemic. Think about an infectious disease outbreak, an Ebola outbreak, what would you do? You'd contain it to prevent more people from getting the infection, and you'd see that the people with the infection are getting life-saving treatment so it doesn't kill them. It's really very similar for our opioid addiction epidemic. The difference, though, is that there is a role, I think, for reducing the supply. And I'm not, by saying that, speaking in favor of a war on drugs, I think it's pretty clear that the war on drugs failed and it contributed significantly to mass incarceration. But there is a role for law enforcement. You do want the black market price for pills and heroin to be high. You do want efforts to try and keep fentanyl out of the country. Making it harder for people who are opioid addicted to access prescription opioids from pill mills or to access heroin while making treatment easier to access would result in many more people seeking treatment. And we could talk a little bit more about that in the discussion. A couple of final points. This is the AIDS epidemic. And you're really looking at deaths from AIDS. And you can see we peaked around 1995 with about 45,000 deaths from AIDS at the peak of the AIDS epidemic. And that's where we are right now with deaths involving opioids. We're at about 45,000. Total number of drug overdose deaths is higher, but opioid deaths are at about 45,000. We're basically where we were at the height of the AIDS epidemic. And if you look at this slide, you'll see that deaths from AIDS plummeted. And why did they plummet? We had the introduction of antiretroviral therapies, medications that would allow us to finally treat HIV infections so that it wasn't a terminal disease that became a chronic condition. I believe that we have medications available today that if there was better access, we could see a similar trend. And the medication that I think really would be most valuable in that regard is buprenorphine or suboxone. And when I say that better access to buprenorphine might allow us to see a similar plummet in deaths, I'm not just speculating. It happened in France. In France, buprenorphine was released in the mid-90s. And there were no limits on who could prescribe it. Doctors didn't have to take a special class an eight-hour course. There were no cap on the number of patients they could treat. It was out there. Doctors began to prescribe it very widely. And within six years of the release of buprenorphine there, you had a 79% drop in deaths from heroin. And you could see here the line going up is buprenorphine prescriptions, the black line going down, or deaths involving heroin. These are some of the different interventions. We'll talk a little bit more about them in the discussion. These are states where prescribing is trending up or down. You see Massachusetts, the prescribing of Massachusetts is in dark blue. We're in the best category. And by the way, Massachusetts is doing a little bit better right now. One would predict that Massachusetts would have a much higher death rate than other parts of the country because we have much more fentanyl. Almost all of our heroin has fentanyl in it or is fentanyl being sold as heroin. So you would predict that the opioid crisis would be worse, which it is, in terms of overdose deaths. But you'd also predict that the trends would be moving in the wrong direction and they're moving in the right direction. So overdose deaths in Massachusetts have stopped going up for the past year, year and a half, may even be trending in the right direction. It's too soon to celebrate. But I don't think it's necessarily because of the drop in prescribing. That helps prevent new people from getting addicted. I think it has more to do with the fact that in Massachusetts there is better access to buprenorphine into treatment than in other parts of the country. Washington State has also done a really good job of focusing early on before other states were on the issue of high dosage prescribing. Back in 2010, the state put out a policy requiring doctors who had patients on doses greater than the equivalent of 120 milligrams of morphine that they would have to take this extra step and seek a consult from a pain specialist. They basically legislated an upper dose limit and that's been, appears to have been very effective in reducing overdose deaths in the state of Washington involving prescription opioids. This is the national overdose death trend. It's flattening. It's possible we're beginning to turn a corner nationally in overdose deaths, it's too soon to tell but this is the best it's looked in a very long time. So maybe overdose deaths are not, I have a feeling they're gonna go up again when we have the 2018 full data but maybe if we're lucky 2018 will be the worst year in history and we'll begin turning a corner on the epidemic. So I'll stop here in summary. This is the worst drug addiction epidemic in the United States history. To bring the problem under control we need evidence-based interventions and we're really not there yet. Thank you. Good afternoon everyone. Just wanna thank Michael, Dr. Seenhot for inviting me here today for all to come. This is like a passion subject for me and also was grateful to meet Dr. Kaladney and all of you. So I'm gonna sort of bring this big picture that Dr. Kaladney has painted of the epidemic down to the Boston streets to try to give you a very downstream, desperate street level first responder perception of what's going on and where we need to go from here. And I'll just very briefly mention that the program that I work for has a very simple mission which is just to provide or short access to the highest quality healthcare for homeless men, women and children in the greater Boston area. And to kind of frame a little bit this problem from my vantage point I thought I needed to give you some context to explain a little bit about what this practice is like and to sort of explain more about the homeless population in Boston which is for whom this epidemic is really magnified and was seen quite a bit earlier. Just the case in so many different conditions. So just to give you some context for me and my colleagues at the intersection of Mass Ave and Albany Street in Boston this is an epidemic that still has not led up and even though the statewide numbers are flattening for the first time that's not happening in our population yet which is not surprising. So drug overdoses actually we know this we're so lucky to have data like this on our own practice. Drug overdoses are actually the leading cause of death. We know this from a very large scale mortality study that we conducted actually a whole decade ago now. So between the years 03 and08 this disease killed more people in the homeless population in Boston than anything else. That study was we published it eventually in JAMA Internal Medicine in 2013 and we started to see this data come back in 2012 and it was just so highly motivating for us. I think I even have a colleague in the audience from those years, Dr. Danji here. I think we were feeling that anecdotally but to see this data come back for us was a big driver. We at that point in our history had been primarily a primary care practice that had grown out of the departments of medicine at Mass General and Boston Medical Center. And this data really we took a very hard look at ourselves. We took a very hard look at our own prescribing practice, wanted to know how much we might be contributing to this epidemic in a population with a very disproportionate amount of chronic pain. We also just sort of took to own addiction as a core part of our program's identity. So there are 30 doctors in my practice, 16 of us have gone back to do to become board certified in addiction medicine. We began in 2012 really prescribing naloxone or Narcan rescue kits to just very broadly across our practice to everyone. We started to triple quadruple the size of our office-based addiction treatment, OBAP programs in which we provide either buprenorphine or suboxone or injectable naltrexone or vivitrol. So these programs were just growing by leaps and bounds in the aftermath of seeing this data. In fact, in the building where I spend most of my time, there are still today between two and five overdoses every single week. It's so common that I wear Narcan on my chain here because I don't always have a bag with me. I'm frequently stopping next to the parking lot where I park to resuscitate someone. I'm very often resuscitating people in public bathrooms nearby when I go to grab a lunch somewhere. I mean, so we are just drowning in overdoses despite a lot of shift in programming in recent years. And so this is just the key figure from the mortality study I mentioned, which I think paints this beautiful picture in one figure of the evolution of a new epidemic in this population. So what we're looking at here are mortality rate ratios. So a rate ratio of one on the x-axis there means that mortality from the causes that you see on the left was the same in two different time periods because we had actually done the same study about 15 years earlier. So this is looking at the rates of death for these causes compared for 03 to 08 compared to 88 to 93. And what you see is that in 88 to 93, so a rate ratio to the left of one means that it was more common in the previous time period. So the rate ratio for HIV and HIV related deaths was far to the left there. There's been a big mitigation in deaths as Dr. Kaladini showed you nationally in this population in Boston. I think the reasons for that as have been mentioned include obviously the advent of highly effective antiretroviral therapy. In my mind they also include things like the Ryan White program that allowed us to bring meds and impressive sort of medication adherence work right to the street. It also included policies having to do with prioritization of people with HIV for housing and many other policies. So deaths from HIV, this was the good news in the study, were mitigated to a large extent but they were almost perfectly offset by a shift to the right in the same amount of death from drug overdose. The size of the box here by the way corresponds to the number of deaths from each cause. I point out just because it's interesting that cancer and heart disease in the very center of this figure were a very close second and third most common cause of death and those did not move across the two time periods which is kind of devastating to see if you're a primary care doc working in this practice. Very motivating data. To paint the picture I thought it would be good to share some photos with you as well. From a news article that the globe ran on the front page and several subsequent pages that was just kind of devastating article in I think this was June of 2016. The title of this article I thought was just so stigmatizing and so nihilistic, life and loss on methadone myel. And the reason people refer to this part of town as methadone myel is that is really stigma. There's so much stigma in lots of different segments here in Boston against methadone which is arguably the most effective treatment that we have for opiate use disorder. And there is a clustering of clinics that can treat people with methadone and other addiction programs in this part of town. There's also interestingly a clustering of homeless shelters. So within about 500 feet of the building that I work in there are 1,100 homeless shelter beds for adults. There's a real clustering of both addiction services and homeless services in this part of town and it's gotten this sort of moniker of methadone myel which is very negative. So all of the pictures in this story are my patients that we know well. They all have the same hopes and fears as you and I do. Some of them are avid readers and their stories are just tremendous. The article focused though in a very negative way and this was a difficult article for us to see. So that's sort of a little bit about the context of where I'm coming from. And I guess what I wanna move to next is explaining two different recent innovations that we've kind of out of desperation really put into place in our practice. And so again I'm explaining that we're seeing an unprecedented number of overdoses in fact every single day. We're growing as quickly as we can access to treatment. So we now have a census in our practice of about 500 people at a time who were treating with buprenorphine, about 100 who were treating with injectable naltrexone or Vivitrol. So we have, Al hasn't been there for a few years and that number is tremendously larger. We're doing this inside of many of the shelter clinics that we work in. We're doing it on the street. We're trying to decrease every barrier basically to getting access to this treatment and behavioral therapies as possible. But despite all of that, the numbers really aren't coming down in my world. And so, and that's sort of the place where we start thinking about innovation and the need for different things. So I'm gonna describe to you, and I thought I would just read a short couple paragraphs that I wrote to explain this about why we started what turns out to be a very provocative program called SPOT in our building. SPOT stands for the supportive place for observation and treatment. I'm gonna tell you about it in a minute. But I wrote this recently. So I think what I began to believe about being innovative is above all else, recognizing and responding to needs that have gone unarticulated, that haven't been voiced or haven't been heard or sometimes needs that have been silenced. And so there are a couple stories that kind of illustrate these unvoiced and unheard needs. The first story is one that plays on repeat for the last several years now and that kind of ultimately led to the creation of SPOT. I can see it so clearly in my mind because it's happened so many times. I'm on the floor of a public restroom in our building. I'm hunched over a young person who I've just revived from an overdose using Narcan and rescue breaths. And as he begins to wake up below me, he's feeling the withdrawal from opioids acutely. He's both disoriented and, one second, my phone's a little funky. There we go. He's both disoriented and afraid. He's half dressed at this point because we've taken off his shirt. He's shaking like a leaf. He's dripping in sweat and he's really completely vulnerable in that moment. And I feel frustrated as do the staff around me because this person is a stranger to us. He isn't well engaged in our clinic because even our services, which are so far from mainstream, are fairly structured. It's hard to imagine that this man sitting in the waiting room of our clinic, there are elements of the way that we operate in the larger healthcare system that simply make him reluctant to engage with us. So when he refuses to go with EMS, and by the way, in Boston right now, in 2018 year to date, 60% of people who overdose, for whom 911 is called, do not go to the hospital. That's how much of a problem we have with people accessing any kind of healthcare for this disease. And there's so many reasons for that. So when he refuses to go with EMS to the hospital because of fears of being stigmatized there and also because he's really not sure what the heck they can do for him, I'm afraid to see him walk out the front door. I don't know whether I'll ever see him again. And all I feel is desperation really to let him know somehow that we're gonna be there for him no matter what happens in the coming hours and days. I wanna know him better. On another morning, like so many others, as I'm walking from the parking garage to our building, I have to steer folks who are heavily sedated away from the dangers of that very busy intersection. So all around me, people are crippled by addiction, by this epidemic of addiction. They are making their way from street to street with heavy bags slung over their shoulders. They're seeking ways to appease their addiction today to keep it at bay just a little longer to soothe themselves for weeks, months, and years of unimaginable trauma. It was countless mornings like this that gave birth to SPOT. Just mornings kind of registering these unvoiced needs of people around our building. Sometimes even my own not fully articulated needs as a doctor. And so let me tell you about SPOT and sort of what's unfolded. So this is an explicitly harm reduction program within a healthcare setting, which is not an easy thing to pull off. It has three simple aims. The first is to prevent fatal overdose. The second is to try to engage a very high-risk population that we're not well engaged with to get to know them better, ultimately to try to help them access treatment and to try to tackle stigma even within our own program. And I'll just say kind of outright that even in a very mission-driven place like a healthcare for the homeless program, there's so much stigma about and really against opiate use disorder in people who use opioids that that is not an insignificant task even in my microcosm. So we essentially kind of dreamt up a space that we knew needed to be street level, a very low barrier to walk into. And we just had a conference room, really is the only space that we could use to convert into this kind of programming. We have space for only 10 people at a time and essentially people use heroin and fentanyl and other sedating substances around our building. And afterwards, they either walk in or are brought in by a peer or brought in by an outreach worker or wheeled in by a police officer, whatever the case may be, but they come in typically still able to talk but already heavily sedated. And they often say, listen, I took a little bit more of this and that than I usually do and I'm not really sure what's gonna happen. Do you mind if I stay here? And it's sort of that simple. And at the point where a person can't walk or talk anymore, we start to monitor their vital signs continuously. So we know exactly when we need to use supplemental oxygen, Narcan, IV fluids even. Our hope though is, and our hope obviously is that people are gonna be able to walk out for another day and that we can engage with them when they're more awake on the way in and on the way out and that we could create some pipelines that are pretty fast track into various types of treatment people might be interested in. So we staff for the medical folks in the room, we staff this space with a registered nurse who specializes in addiction. We have quite a bit of non-clinical staffing and really our harm reduction specialist we call her is sort of the linchpin to the program. The person that most people trust the most and are willing to engage with more. Sometimes we have peers in the room and then we have a rapid response clinician in the background, in the building to respond when things go south, which is not uncommon. So these are some pretty striking and worrisome vital signs that are common in this room. So in yellow here are blood pressures, you're seeing a few here that are just quite low. The pulse is in green and it's common in this room for us to see pulses in the 30s and 40s. And then in blue here is oxygen level and these are actually normal oxygen levels. So one of the first things we started to learn when we could actually monitor people in the course of an overdose is that at least in our microcosm on the corner of Albany Street and Mass Ave, people are combining five substances. They're sold together as a cocktail, they're called the cocktail. And they consist of an opioid of any sort, most typically heroin or actually fentanyl. A benzodiazepine of any sort, although clonazepam or clonopin is definitely preferred and has the highest market value. Gabapentin or Neurontin. Clonidine, which is another prescription medication with several different indications that I think is driving a lot of the vital sign abnormality we see and we're trying to show that at the moment. But that prescribers aren't really aware of the way that it's being used. And the fifth one at the moment is Prochlorperazine or Fenergan, which is an anti-nausea medication that we use for lots of reasons. And so, and what I'm learning in this room, what we're learning is, and people are talking to us here in a very different way than they do in any other clinical setting that I've been in. What I'm learning is that when people have a tolerance to a certain amount of heroin or fentanyl or whatever opioid that they can not get additional euphoria or high, but they can get additional sedation. And my patients basically say, I am trying to check out. I don't wanna see this environment around me. I don't wanna exist in this world today. I want to be asleep through the most of today. And it's sedation that they're actually after. And that's absolutely happening. There's some examples of the kinds of things we're beginning to learn in this room. The cohort who use the program are extremely high risk. They're experiencing repeated overdoses. They are not engaged with healthcare providers in general. Again, the nature of the relationship in the program is very different than in any other clinical setting I've been in. And I've just explained to you a bit about the cocktail. So we've actually been open now for a little over two years. And I'll say it was a battle to be able to open. NPR ran a story that we were planning to do this and out of the blue, that same day, the mayor of Boston had 75 phone calls from people who live in the South End. The governor got asked about it at a press conference in Worcester three days later. And it sort of blew up as something much more controversial than we were naively thinking it would be. And so we had to kind of go back to the drawing board and for about six months we did a lot of community processing. I think we probably attended 55 community meetings. We brought people into the space. We explained what we were going to try to do. And we tried to build some community buy-in and that eventually happened. So we opened in April of 2016. And in this tiny room with just space for 10 people we've had actually at this point now two and a quarter years and we've had about 8,000 encounters with about 700 unique people. And I think some of the outcomes that most people are interested in are how often do we connect people to treatment? And I'll say that I think there's value in this kind of service, this kind of harm reduction work even when we can't connect people to treatment. This is a day that they are going to live. There's gonna be a tomorrow. We're gonna make sure that they're not gonna die. My hope eventually for everyone is that they connect to treatment but there is value even when that doesn't happen. Our success rate in connecting people to treatment in the first year was only about 10% which doesn't surprise me too much. And by the end of the second year now we're at 22%. I'll tell you that it happens on average at the 13th encounter which really says something about building trust and relationship and engagement over time. We just launched a really neat campaign, public campaign to try to combat stigma, the kind of overlapping intersecting stigmas of homelessness and addiction. It's called the Boston Underdogs Campaign and we had this amazing marketing firm Hill Holiday help us out with it. And so if you're interested in hearing a couple stories from people who have been to spot and learn more about it, you can check us out on that website. So I'm gonna tell you briefly about a second, a second recent intervention that's only about seven months old now that is again coming from a place of desperation. So despite the fact that again, we've been trying to lower every barrier we can to people being able to access buprenorphine treatment or suboxone treatment, we're still finding that there are wait times even in our clinic. If you walk in and say, I am looking for treatment with this medication, it's gonna take us about eight weeks to actually write the first prescription. And there are typically hoops that you jump through while you're waiting those eight weeks. And by the way, death rates from overdose are the highest in the wait list period for both buprenorphine and methadone. So we decided to try something new and we're lucky enough to have a group of funders sort of be willing to pilot this and this primarily being funded by the Kraft Center for Community Health and the GE Foundation and a few others. But we basically decided that we wanted to create a mobile program of addiction treatment in which we would combine a clinical partner, in our case addiction medicine people from our community health center with a harm reduction partner. The harm reduction partner here is our state's largest syringe exchange program, a hope. And that partner by the way to me is like absolutely key. We wanna be mobile and we wanna be able to hotspot. We wanna be able to go geographically to the parts of Boston where the most overdoses are happening. So we looked at a ton of maps like this. This is a heat map dated now in that it's 2016 but it basically shows you for that year the hotspots of overdose. And this comes from Boston EMS data. These are incidents of what they call narcotic related illness which is overdose. And to me, this is a map of homelessness in Boston. Although I'm sure that doesn't tell the whole story because we're looking at first of all, the part of town where I was telling you about the clustering is here. I'm gonna call it recovery road instead of that other moniker. And then lots of these other dots are T stops, T stations, North stations, South station. These are places where my patients stay. They use the bathrooms. They're hidden in alleyways of the T stops that you would never know about. These are also shelters. Pine Street Inn is a small blip on this map, et cetera. And so Dudley Square as well over here which is a part of town in which there are fewer outreach services, fewer addiction treatment options. So we basically decided we wanna go to these places. We wanna kinda take it down to the street level. We wanna make it possible to engage with people outside, networks of injection drug users. We wanna learn the networks. We want to be able to find people. And if they don't want treatment right now, there's actually quite a bit that we can do. We can do syringe exchange. We can make sure that they're gonna use a clean unused needle every single time that they inject. We can take the used needles so they're not thrown away because there's no other place to dispose of them. We can distribute Narcan. We can give water. We can give all the rest of the works, so to speak, that it takes to inject heroin without the risk of infection with HIV and Hep C. So we can do a lot, even if someone doesn't want treatment. But if you want treatment, we're gonna do it right here right now. No barriers. I'm gonna make sure you have health insurance right here right now. I'm gonna sign you up if you don't. I'm gonna take you myself to the pharmacy. We're gonna fill this prescription together. We're gonna do an induction right here on the street. We're gonna just try to get rid of every barrier. And this is sort of what our amazing fund van looks like. We got the Winnebago company to build it for us. It has a very small examination room in the back. It has a phenomenal kind of wifi router, computer. I have access to Epic printer or label printer. It has a vaccine refrigerator. So at the moment I'm doing a ton of Hepatitis A and B vaccines because there are outbreaks of both of those infections in this exact population. I am able to hand out post-exposure prophylaxis for HIV to start people on pre-exposure prophylaxis for HIV. It's sort of like a addiction one stop. Doing a ton of wound care, taking care of abscesses that people develop when they inject. In the reception area, that's sort of the part where most of the syringe exchange work is happening. And by the way, I'm learning so much. We're learning so much in doing this project. We're learning that there are so many people who never make it into the doorways of our hospitals and community health centers. And we're learning about things like secondary syringe exchange where you can engage a key person in a network of injection drug users. That person is willing to take more needles distributed in their network, bring back more from their network in the same thing with Narcan. So this is sort of what our version of patient-centered care looks like. We go out in teams of three and four, the prescriber and the outreach workers, public health advocates from the syringe exchange program. We tend to park in a very quiet, try-to-be-subtle place and then we blanket a neighborhood. We are mostly working in alleyways. We bring people back to the van when that's necessary. I think I'm not gonna bore you with some of our early data because it's only been about six months now. But you'll see in these different neighborhoods that we're going to some of these hotspots, we've actually distributed quite a few needles and we're actually bringing back more than that. So our exchange rate is about 112% right now. We've distributed close to 1,000 Narcan kits. We're having clinical encounters now with about 100 people so far. And actually I should tell you we're only working half time on the van. So at the moment we've started and have a census of about 30 patients on buprenorphine and we're prescribing it even in a very different way. It's, we'll call it sort of low threshold buprenorphine, low threshold to start to try it to keep working with people beyond relapse. And that's sort of what we're interested in doing. So where do we go from here? Which is really kind of the interesting topic of the day. I would say first and foremost that we need a massive infusion of resources for this epidemic to manage it in this country. Something akin even to the Ryan White Care Act. We obviously need a multifaceted approach and I would add continuing to try to tackle stigma with public campaigns and the stigma not only of the addiction itself but the stigma associated with the treatments like buprenorphine and methadone. I think there can be a lot done as Dr. Kaladani also alluded to on the prevention side. But I am so far downstream that I'm focused right now on expanding access to low barrier treatment. And finally, and I think just as importantly on harm reduction. I think these services play a crucial and complementary role really in a treatment continuum. I think we have to be willing to build trusting relationships with people who use drugs that might need to take us out of our comfort zones. I think there's the offer of the promise of discovering and tailoring interventions that have high impact that we should be testing everywhere right now. And then finally, as part of a robust harm reduction strategy I do think that in certain parts of the US and certain urban areas in particular that supervised injection or supervised consumption sites make a lot of sense. And I'm happy to say a little more about those in the discussion period. I think I'm gonna stop here. Thank you. So I'm gonna start us off with a couple of questions. First question relates to a lot of the work that we do at Portal, which is drug pricing. We do have some concerns about price increases in the high costs. So as I mentioned, Narcan being acquired by another company, concern that mergers often lead to price increases soon after acquisitions. And then also concern about the president's plan to include Vivitrol, which is of course a very expensive branded medication as part of the response. Do you guys have any thoughts about that? So, let me start with Vivitrol. And there's three medications that are used for treating opioid addiction, buprenorphine methadone and extended release naltrexone, which is called Vivitrol. And we don't really have good evidence to tell us how to position the treatment, which medicine is right for which patient. And unfortunately, what we hear from the National Institutes of Drug Abuse or from American Society of Addiction Medicine, when they discuss the different medications, often they talk about all three as if they're all equal, like they don't wanna pick favorites. And that's not a good idea because even though we don't have great evidence about how to position treatment, we do have evidence that opioid agonist treatment with buprenorphine and methadone maintenance is more effective than Vivitrol. Problem with Vivitrol is that you see very high dropout rates and the manufacturer sat on the results of a registry trial with about 400 patients that showed that within the first few months of treatment, about 75% of the patients had dropped out. They didn't come back for their injection. And when, if you give somebody naltrexone, the brain, one of the ways in which the brain compensates by having its opiate receptors blocked is that it upregulates opiate receptors. It produces more opiate receptors, which isn't a problem having a brain with lots of extra opiate receptors if you get your injection every month. But if you miss your injection and you have a brain with lots of extra opiate receptors, you've created an individual who's super sensitive to opiates. It's somebody who doesn't just have a normal tolerance, like someone who got out of jail, you've made them super sensitive. And there are many reports now, including one published paper showing high rates of deaths in patients treated with Vivitrol. We don't have good evidence about how to position the treatments where I, based on my clinical experience and the evidence we do have, I think extended release naltrexone makes some sense in patients who haven't been addicted for very long, a young person who's been dabbling, short history of opioid addiction, low physiological dependence on opiates. It's worth giving the medicine a try, but in patients moderate to severe opioid use disorder, for example, heroin injectors are the type of patient you're more likely to encounter in the criminal justice system. These are patients who are better, more appropriately treated with buprenorphine or methadone maintenance. And yet in the criminal justice system is where you see a very strong bias against opioid agonist treatment and drug court judges who'll say, we're only gonna use Vivitrol in our court and our drug court program. And the manufacturer has been very good about playing up the fears of buprenorphine and methadone, and they've been very effective on Capitol Hill, which is why we had inserted into federal legislation, not even equal footing for Vivitrol, but really giving the promoting of extent release naltrexone. I'm just on Narcan and we've got the expert here, so I'm gonna really defer to Jesse on this. But we've made very good progress in the United States over the past 10, 15 years in making naloxone more available. And in many municipalities, it's carried by first responders, it's being distributed by syringe exchange programs. And there are other states that have made it available over the counter, and all of that is sort of a no brainer. We absolutely have to do that and we have to keep doing it and we can do even better. Anyplace, even in a Starbucks, there should be naloxone because people are overdosing in the restroom there on airplanes. We should be doing this, but despite these great efforts, and despite the fact that we're saving many lives by making naloxone more available, as you know, opioid crisis has really been continuing to worsen and so it's necessary, but not sufficient. If you rescue somebody with naloxone and you don't see that they get treated for their opioid addiction, you just have to hope somebody's around with naloxone the next time they overdose. And many overdoses occur without a peer around or without somebody who can rescue you. And many deaths occur and people sleep, particularly prescription opioid deaths. People don't wake up in the morning. There is no opportunity to administer naloxone so it's only gonna get us so far. I just, I thought I would tell you how much Narcan cost at the moment. I'm terrified about the cost going up with this shift. So a year ago, we were paying directly the company that makes the high-dose Narcan, which is what you need in Massachusetts. These are four milligrams of Narcan in a 0.1cc of fluid, which is just very potent. And I typically need three of these to reverse one overdose right now. That tells you a lot about the supply here. But a box of two of these was costing us $150. So we have to buy them for our staff. Our patients are mostly covered by Medicaid. We do have some people without health insurance that we buy these for and was costing us $150. Recently talked them down to a public interest price of $75 a box. So it's still actually really costly, especially when you think of how much we're going through here. So, and that's like considered a great price, $75 for eight milligrams of Narcan. So I'm very worried about it going up. And I think the Department of Public Health is as well in Massachusetts. A related question. What are your thoughts on the FDA's role both in creating and mitigating the opioid crisis? And do you agree with their approach to new opioid drug approval, which is largely centered around the development and approval of abuse deterrent formulations of opioids? So I don't think, I honestly do not believe that we would have an opioid addiction epidemic today if the FDA had been doing its job properly. If it had properly enforced existing federal law, I don't believe we'd be here. The Food Drug and Cosmetic Act and Aaron is really an expert on this, but what that law says is that a drug company is not allowed to promote a medication for conditions where it hasn't been proven safe and effective. And if FDA had been enforcing that law, when Purdue introduced OxyContin, and it really hits the market in 96, it gets approved in 95, had they properly enforced the law, they would have told Purdue, great, you've got extended release Oxycodone. The benefits of that drug may outweigh its risks when it's used in palliative care. We're gonna give you an indication for palliative care. We're gonna let you send your sales reps and out to the hospices and to the oncologist's offices and the palliative care docs. But there is no evidence that the benefits outweigh the risks when it's used for low back pain with a normal spine, chronic headache, fibromyalgia, wisdom teeth extraction. The risks sound like they outweigh the benefits and we don't have evidence of safety and efficacy. So no, we're not gonna let you promote for those conditions. Had they done that, I don't think we would be here today, but they didn't do that. And very immediately Purdue was promoting OxyContin and other opioid manufacturers with their opioids started to do the same thing for long-term use as safe and effective and FDA allowed that. And by 2002, it was very clear that prescribing had taken off at a level far greater than clinically, could be clinically needed. There were reports of overdose to acid and addiction coming out of New England and Appalachia and members of Congress were beginning to hear from constituents and FDA is beginning to hear from members of Congress and they start to hold hearings and they start to hold an advisory committee meeting and they invite some experts to consult to sit on this advisory committee. And they asked the experts a couple of good questions. They said, should we narrow the indication so that the drugs can't be promoted so broadly? And should we change the way we're approving these drugs because at this point, lots of drug companies like this model of taking an old generic drug and repackaging it as an extended release and promoting it for chronic pain. It's become a billion dollar blockbuster drug for Purdue. They want to get their product. So a lot of companies have their applications in and FDA says, should we be changing the way we're approving them and should we narrow the indication? And the experts who they brought together to consult happened to be some of the same experts who were leading this campaign in the medical community to increase prescribing who had helped usher in the pain is the fifth vital sign and had been teaching the medical community that we shouldn't worry about the risk of addiction. And so they asked the champions of this crusade for more opioid prescribing, should we better regulate the manufacturers, experts who were getting paid by the manufacturers? And of course they said, no, don't change a thing. And the FDA actually went in the opposite direction. Instead of making it harder for new opioids to enter the market, they changed the way clinical trials were being done to demonstrate efficacy in a way that made it much easier. And we wound up with a steady stream of new opioids and each time a new opioid hit the market, the manufacturer costs a lot of money to bring a drug to market. The only way you're gonna recoup that investment is by getting doctors to prescribe your new product. And they're only way they're gonna know about your new product is if you're out there promoting it, visiting doctors and advertising it. And so each time a new opioid hit the market, it was like pouring fuel on the fire. And now the FDA still hasn't really changed anything. They're sort of latching onto abuse deterrent formulations which are really not much better than a gimmick. Making a pill harder to crush for snorting or injecting is not making that active ingredient any less addictive. This was a question submitted via Twitter a few days ago. How do you propose balancing, reducing opioid abuse and illegal use with reducing the stigma for those who need opioids for chronic pain and who use them properly and responsibly? So I mean, I think the way that question is framed suggests really a misunderstanding of the opioid crisis. And there are many people with chronic pain who believe and they've been led to believe this in part who believe that they're being punished for the bad behavior of the drug abusers and where we take our opioids responsibly. Opioids are helping us and there's those drug addicts. I hate that term, but that's basically what they say. And we're patients, not addicts. And because of those addicts, we're having a harder time and so that there should be this balanced approach. What about us? And the reality is these individuals who are on chronic opioids, particularly those who are on very high doses, are beginning to have a harder time finding doctors who will continue them on such high doses. And it is very hard for people to come off and the medical community is beginning to get the message that we shouldn't have put all of these people on opioids. But that doesn't mean that opioids are really helping them. Some of these people who are doing okay, I believe they're doing okay despite being on opioids, not because of the opioids. And I don't believe we should be forcing them off of opioids now that we've realized we made this horrible mistake. I think a good way of thinking about this is if you think about estrogen replacement therapy. When I was in medical school, working in the primary care clinic as a medical student, we were taught basically to twist the arms of our patients, post-metapausal women, and get them on estrogen replacement therapy. And we were told that we were taught that when they said, well, what about increased risk of breast cancer to let them know that there really isn't good evidence suggesting that and heart disease is the biggest killer of women. And this is gonna lower your risk of heart disease. And we put every patient, and when you got a woman to agree to go on it, you felt like you did something good. And a couple of years later, in 2002, I think, a paper comes out, I think in JAMA, and the medical community figures out, wow, boy, were we wrong. It wasn't an insignificant increased risk of breast cancer. There was a very significant increased risk of estrogen-sensitive breast cancer, and it wasn't reducing risk of heart disease. And almost on a dime, we were able to stop. And when you look at the epidemiology of estrogen-sensitive breast cancer, you can see where medical practice begins to change, and you see estrogen-sensitive breast cancer rate starts to drop. We're at a similar point with opioids. The difference is we can't really stop on a dime. Millions of these people who were put on long-term opioids, really victims of our era of aggressive prescribing, are not gonna be able to come off easily simply because we figured out that we made a horrible mistake and we haven't really had a good discussion or good policies really about how to address the needs of that population. I mean, I do think that there is a place for opioids in treating chronic pain. I think there are patients who need opioids for chronic pain to be able to function. I think we've gone way overboard as a prescribing community. I think we have not recognized just how high the risks are as we've initiated opioids over actually now many decades. And I think that that's getting better. I do think there's a balance. I still don't think we're there yet, though. I think we're, my own personal opinion is we are probably still over prescribing more than we should be. I think we're, I mean, I have a skewed vantage point because I see the risk side. Way downstream. But I also recognize that there are, there is some pain for which chronic opioid therapy is helpful and it helps people function well. So I think there is a balance, but I don't think we've reached where we need to be yet. And we can open it up for audience questions. We're kind of running out of time, but maybe if there are a few questions, I can take a few and then we can have our experts respond to all of them. So any hands? Thank you. Hi, I'm the director of patient advocacy at Boston Medical Center. So we live this daily as well. Thank you both very, very much. I'm just wondering about supervised injection facilities. What are the current barriers to having them legislated and are those barriers insurmountable or will we see them? Couple more. Thanks, Erin. Hi, my name is Martha Yorchak. I'm at Pergamon Women's Hospital in charge of the ethics service. The data you reported in France about buprenorphine availability was very impressive and I wonder if you can speak to one of the resistances here and do you see them being overcome? Maybe one more? Thanks. Hi, I'm Corey Gerlach. I'm a PhD student at Harvard Medical School and I was wondering, Dr. Gayeta, you talked about treatment and I was wondering how you define treatment and whether you mean patients that are taking Vivitrol or whether you're talking about 12-step programs and to both of you, just what do you think, do you think this is a problem that could be solved by the medical community and the drug industry alone or is there a role in 12-step programs and things like that? That's a lot. So we start with a question about supervised injection. You asked really about barriers and I would say that, I mean, so legally there are, there is a federal controlled substances act that has a crack house statute created in the late 80s really in response to a cocaine epidemic that makes it illegal for anyone to operate a facility in which an illegal substance is used. So there's a federal law that is in place to prevent that from happening and then each state has its own controlled substances act and in Massachusetts we have a very similar statute to the crack house statute and so the barriers, and I'm just gonna tell you the local barriers in this state, although it's a little bit different in California, a little bit different in New York, a little bit different in Philadelphia and in Washington state right now. Those are the places that are sort of leading on this possibility. In Massachusetts, I think one strategy that I think we need at this point in the epidemic, especially that it's, especially to address the fentanyl epidemic, I think we need to be able to be with people at the point of injection because fentanyl is so fast acting and so I would argue that we could ask our state legislature or our governor for an amendment in the setting of a public health crisis to at least pilot a medically supervised injection facility. I think that there's more than enough evidence from other countries where these facilities exist to strongly suggest that the outcomes would be favorable. But even if that happened, and of course there's, I think that the legislature in Massachusetts struggles with this, I think the administration struggles with this, but even if we were to convince our state legislators and elected officials to try this, we then would have to have some level of reassurance from the federal government that they wouldn't come in to stop and actually the opposite is true. So we now have the U.S. Attorney General's office very explicitly in the New York Times two weeks ago threatening anybody who tried to open such a facility of being shut down and jailed. So there's quite a bit of barrier right now on the federal level. I'd say there's less barrier in a few different states. Massachusetts is one of them. So the governor's most recent opioid care act 3.0 that passed this past in mid-August, there was an addendum that are an amendment to that law that almost squeaked through to ask the state to pilot a SIF. It got watered down to creating a commission to look at the possibility and the feasibility of opening a SIF in Massachusetts and that commission is supposed to give recommendations to the legislature in February. So there's quite a bit of barrier. And I think the main thing that people struggle with in this concept is, and I hear this all the time, is that they worry that if you open a facility like this that people will be enabled to use heroin that will somehow encourage use even. And I just have the exact opposite view that the use is happening anyway. And in my world it's happening in very dark alleyways and in bathrooms and in places where there's some privacy and trying to sort of escape. And so I think we need to bring it out of that shadow and into the light. I think I've got so many examples of cases from spot where someone walks out that day, I know they're gonna use, they know they're gonna use. I wanna be able to say to them, you know what, you have worth and I'm just gonna be with you today. Even though that's what's gonna happen, just stay. You're gonna be safe. I'm gonna keep you here. I don't know what will happen in the future but right now at this injection you are not going to die. So any case, quick answer about barriers to SIF legally and then just in terms of public opinion and stigma about that intervention. There's the evidence base for SIFs from other countries is pretty dramatic. And they've actually ways to try to study this enabling question that I think have more than given us of enough evidence that we should be trying this right now in the U.S. in the middle of a fentanyl epidemic. Do you have anything on that one? I'd like to see some SIFs piloted in urban areas. I don't, I agree with you that they wouldn't enable or that's not government sanctioning use. I don't see any downsides to SIFs and I think they could potentially be helpful. The data isn't as clear as it is, for example, with syringe exchange and we understand that clean syringes can reduce HIV infection. Doesn't work as great for a hep C but we had good evidence on syringe exchange. We don't have the same evidence and some of their papers are conflicting but I think we should be piloting this. I get a little concerned because of the controversy around it, I think it can be a distraction. And while I do think that they'd be useful in urban areas where people are injecting in public spaces where you have needle parks and I do think that they could be good places to link people to treatment, some of the debate is raging in places where I think it makes no sense for a safe injection facility like Ethica New York. In rural or suburban communities, I don't believe people are gonna commute into town multiple times a day. Even though it might be safer to inject in a supervised area, I don't think they'd use them. I don't think they'd risk being seen by their neighbors and I think where people have homes, even though it's riskier, I think many people would inject there and I think that they'd sit empty. And yet in Ethica New York, you had this debate raging between the mayor and the harm reduction community and the press was covering this. And meanwhile in Ethica New York, there was a waiting list for people to access buprenorphine treatment with people dying of overdoses on that waiting list. I'm not sure what the mayor was doing about that. Yet he was the champion of the harm reduction community for proposing a safe injection facility in a place where I think it would have sat empty. I think the focus on it, I think the media likes to focus on controversial issues, but I think the discussion is a little bit of a distraction. There are things we could be doing that we're not doing that would be saving lives that I think would save many more lives. Second question. So that's a good lead into the second question. The case in France and whether there are barriers to implementing that similar scenario here in the U.S. So I think the single biggest barrier and what really more than anything else makes the United States different from France. There are different barriers to buprenorphine like patient caps. For a while we wouldn't let physician, nurse practitioners or physicians, assistants prescribe. There are different barriers. We don't have really good addiction treatment integrated into primary care, but I think the single biggest barrier, the biggest problem is the eight hour training requirement. Not that it's bad for people to learn about a medication before prescribing it, but when you have an eight hour training requirement and a waiver process where a doctor then has to apply to the federal government, what happens is most prescribers will never take that course and in the United States only 94% of physicians are not eligible to prescribe. And so what that means is that a patient who's opioid addicted who may wanna open up to their primary care doc and discuss this highly stigmatized condition and ask that prescriber, that physician or clinician for help if they do that. Many don't, but if they do that and in all likelihood their primary care clinician is gonna have to say, well let's find you someplace to go. And if it weren't for that eight hour training requirement, that primary care clinician could say, well let's figure out how to get you on this medicine. Maybe I need to learn a little bit about it, but I'll try and do it. And it'd be far easier to integrate this into primary care setting. So more than any other barrier, I think that's what makes us different from France where doctors just started to prescribe it. I will mention that in France it wasn't a perfectly rosy story. They were using subutex, which is the pure buprenorphine, which is the easier to inject version. You can still inject suboxone, buprenorphine with naloxone in it, but it's a little less attractive for injection use. And a lot of it did wind up diverted onto the black market people. You can get a high if you inject it. And there was a fair amount of injection use, but because the pharmacology of buprenorphine is unique, it's a partial agonist, even if you're injecting it, it's pretty difficult to overdose on it. And so the overdose death rate dropped. And of course many people who got it weren't injecting it, but were taking it appropriately in a way in which it dramatically improved the quality of their life and their ability to function. I'll just mention a couple other barriers in addition to the training that you focused on. I mean, one is stigma. I think that we've talked about this already a couple of times. The opiate agonist treatments both are just highly stigmatized by law enforcement. They're actually still stigmatized by the DEA. And if you just look at the way that the regulation in place around both the prescribing of buprenorphine and even more so methadone, they make it difficult to provide these treatments. I mean, it is just an example. As a primary care doctor, I've had at least three now random visits from a DEA officer to ask me in a very intimidating way about what I'm doing to prevent diversion and how I'm making sure that I'm below my cap of X number of patients and that type of thing. So the message is very different with the prescribing of these medications than anything else that we prescribe. And the stigma exists even among patients and in families where there's worry that if you're using an open agonist to treat addiction that it's no different than that person taking heroin, for example, when it's absolutely different. In fact, just by the very definition of addiction being compulsive use of a substance despite harm, when the compulsion goes away, the behaviors change and the very nature of addiction itself can go away for some people and that's what we're aiming for. But there's a lot of stigma even beyond the, there's a lot of stigma in society about these treatments. There's other issues too which is that from the point of view of a primary care doctor that this is very intensive work. It's not unlike treating chronic complex heart disease. And I need a team of people to help me do this. I can't do it alone. In fact, even some of the regulation around what's expected of me every time I write that prescription is that visit is taking me much longer than so many other things I do. I think combining buprenorphine, for example, with office-based behavioral therapies and the cognitive behavioral therapy is ideal and yet the opportunity to do that is limited by space and resources and additional team members. So I think there are some logistical reasons why it can be hard or overwhelming to have a lot of patients on buprenorphine in your practice as a primary care doc. So there are a lot of barriers still. So I think we're unfortunately at the end of our time. So thank you very much to the experts and the moderator and thanks everybody for coming.