>> I'M NORA VOLKOW, I'M THE DIRECTOR OF THE NATIONAL INSTITUTE ON DRUG ABUSE, AND IT IS MY PLEASURE TO WELCOME YOU TO THE DAY 3 NIH HEAL MEETING. DURING THIS STUDY TODAY WE HAVE COVERED AN ENORMOUS AMOUNT OF GROUND THRA IS PERTAINING TO OPIOID AND PAIN. ON MONDAY WE HEARD A REALLY INSPIRING OPENING BETWEEN DR. FRANCIS COLLINS AND DR. MURPHY ON EMOTIONAL WELL BEING AND THE IMPACT OF SOCIAL ISOLATION DURING THE PANDEMIC BOTH ON OUR MENTAL HEALTH AS WELL AS ON SUBSTANCE USE DISORDERS IN GENERAL. THIS WAS THEN FOLLOWED BY PRESENTATIONS AND DISCUSSIONS RELATED TO NUMBER 1, STRENGTHS IN THE OPIOID CRISIS, 2 WAYS TO IMPROVE DATA HARMONIZATION AND 3, RESEARCH TO ADVANCE TREATING PAIN AND OPIOID USE DISORDERS. YESTERDAY WE SPOKE ON SOME WAYS HEAL IS ENGAGING COMMUNITIES IN RESEARCH DESIGN AND IMPLEMENTATION AND ADVANCES IN EQUITY AND INCLUSION. THERE WAS ALSO ROBUST DISCUSSION ON A NUMBER OF CROSS KITTING ISSUES SUCH AS ARTIFICIAL INTELLIGENCE, TRANSLATIONAL PIPELINE AND RESEARCH DISSEMINATION. TODAY, OUR FINAL DAY OF THE MEETING, WE WILL BEGIN WITH A PLENARY SESSION ON THE COMPLETION OF NATIONAL PUBLIC HEALTH CRISIS FOLLOWED BY A PANEL DISCUSSION ON ADAPTING IN A TIME OF CHANGE. BOTH SESSIONS WILL BE FACILITATED BY MY COLLEAGUE DR. SHANNON PHAM, DIRECTOR OF THE NATIONAL INSTITUTE OF NURSING RESEARCH. BEFORE JOINING NIH SHE WAS A NURSING COLLEGIATE PROFESSOR IN THE DEPARTMENT OF POPULATION HEALTH AT NURSING SCIENCES AT THE UNIVERSITY OF ILLINOIS CHICAGO COLLEGE OF NURSING AND A FELLOW AT THE UNIVERSITY OF OF ILLINOIS CHICAGO INSTITUTE FOR HEALTH RESEARCH AND POLICY. DR. SANS OWN RESEARCH FOCUSES ON SOCIAL INEQUITIES AND HEALTH AND ALSO IDENTIFYING EFFECTIVE MULTILEVEL APPROACHES TO IMPROVE HEALTH AND ELIMINATE RACIAL ETHNIC AND SOCIOECONOMIC HEALTH DISPARITIES. IT IS MY GREAT PLEASURE TO TURN THINGS OVER TO HER TO FACILITATE THIS NEXT PLENARY PANEL. DOCTOR, WELCOME. >> THANK YOU, NORA, AND I WANT TO THANK MY PARTNER FOR THESE SESSIONS, DR. TISHA WILENTIOUS Y FROM THE CENTER ON DRUG ABUSE. SO WELCOME TO TODAY'S FIRST PLENARY, THE COVID PANDEMIC AND OVERDOSE HAS CHALLENGED OUR SOCIETY IN UNPRECEDENTED WAYS THROUGH ECONOMIC AND OTHER STRESSORS, SOCIAL ISOLATION, JUGGLING WORK WITH CARE GIVING RESPONSIBILITIES AND THE LIST GOES ON. AS WE'VE MOVED FORWARD IT'S IMPORTANT TO REFLECT ON WHAT WE CAN TAKE AWAY TO IMPROVE OUR RESPONSE TO THESE ONGOING AND FUTURE PUBLIC HEALTH CRISIS. AT THE NATIONAL INSTITUTE OF NURSING RESEARCH, THESE PUBLIC HEALTH CRISIS HAVE REINFORCED OUR COMMITMENTS TO RESEARCH THAT ADVANCES HEALTH EQUITY. THAT PROVIDED THE PERFECT STORM FOR THESE CRISIS TO ARISE AND COLLIDE. NURSES PLAY A CRITICAL ROLE IN PREVENTION, DIAGNOSIS AND TREATMENT AND CARE ACROSS A HOST OF THE CLINICAL AND COMMUNITY SETTINGS, INCLUDING HOSPITALS AND CLINICS, PEOPLE'S HOMES, SCHOOLS, WORKPLACES AND JUSTICE SETTINGS THAT ARE KEY TO ADDRESSING THESE CRISIS. AND THIS REACH ALONG WITH NURSES WHOLISTIC PERSPECTIVE AND CULTIVATED KNOWLEDGE OF PEOPLE, FAMILIES AND COMMUNITIES IDEALLY POSITIONS NURSING SCIENCE TO MEANINGFULLY CONTRIBUTE TO ADDRESSING THESE CRISIS. THIS INCLUDES DEVELOPING TREATMENT STRATEGIES FOR PAIN AND SUBSTANCE USE THAT WORK WITHIN THE REALITIES OF PEOPLE'S LIVES. AND IDENTIFYING PREVENTION STRATEGIES THAT PROMOTE--THAT BOTH ALLEVIATE THE CONDITIONS OF DAILY LIFE THAT MAKE PEOPLE VULNERABLE TO PAIN AND SUBSTANCE USE IN THE FIRST PLACE, AND BOLSTER PEOPLE'S RESILIENCE. THE SPEAKERS IN THE PLENARY AND PANEL SPAN THE ENTIRE CONTINUUM FROM PAIN TO ADDICTION AND SETTINGS AS DIVERSE AS EMERGENCY, PRIMARY CARE, PREVENTION AND JUSTICE DEPARTMENTS. ALL OF THESE SETTINGS HAVE BEEN PRECEPTED WITH CHALLENGES IN THE LAST YEAR YET RESEARCH TEAMS HAVE PIVOTED, FOUND OPPORTUNITIES TO ADAPT AND PRESS FORWARD, FOSTER THEIR PARTNERSHIPS AND ULTIMATELY CONTINUE TO FIND WAYS TO CONDUCT RESEARCH THAT CAN HELP US BEGIN TO REDUCE DEATHS FROM THE OPIOID CRISIS. OUR SPEAKERS WILL EACH SHARE LESSONS LEARNED, CREATIVE RESPONSES AND EVEN SOME SILVER LININGS FROM THE COLLISION OF PUBLIC HEALTH CRISIS. I'M VERY EXCITED TO HEAR FROM OUR 2 PLENARY SPEAKERS ON THEIR THOUGHTS ABOUT WHAT MIGHT BE ENDURING CHANGES FROM COVID-19 FOR RESEARCH IN CLINICAL PRACTICE RELATED TO PAIN AND SUBSTANCE USE. AND NOW I'M PLEASED TO INTRODUCE OUR FIRST PLENARY SPEAKER DR. LYNN DEBAR IS A KISER PERMANENTE WASHINGTON HEGHT RESEARCH INSTITUTE, AS A BEHAVIORIAL RESEARCHER HER WORK IN RECENT YEARS HAS FOCUSED ON HEALTHCARE SERVICE NEEDS OF PATIENTS WITH CHRONIC PAIN. PARTICULARLY THOSE WITH COMPLICATING CO MORBID CONDITIONS. HER PROJECTS INCLUDE LARGE SCALE EPIDEMIOLOGIC STUDIES, EXAMINING THE IMPACT OF HEALTHCARE POLICIES ON PATIENT RECEIPT OF PAIN RELATED NONPHARMACOLOGICAL TREATMENTS INCLUDING COMPLIMENTARY AND INTEGRATIVE HEALTHCARE SERVICES. HER PROJECTS ALSO INCLUDE PRAGMATIC TRIALS OF BIOPSYCHOSOCIAL TREATMENT APPROACHES FOR PATIENTS WITH PAIN IN PRIMARY CARE SETTINGS. WELCOME DR. DEBAR. >> THANKS SO MUCH SHANNON AND THANKS VERY MUCH TO REBECCA BAKER AND FOR LINDA PORTER FOR THE INVITATION TO PRESENT TO YOU ALL TODAY. WE DECIDED WE WOULD SPLIT THIS AND I WOULD PRIMARILY FOCUS ON PAIN AND HE WOULD PRIMARILY FOCUS ON ADDICTIONS BUT THERE'S PROBABLY SOME OVERLAP HERE. NEXT SLIDE, PLEASE. SO I WANTED TO RECOGNIZE THAT WE'VE BEEN REALLY FORTUNATE TO HAVE 3 LARGE PRAGMATIC TRIALS THAT ARE HEAL SUPPORTED AND I'VE LISTED THOSE HERE, 1 THROUGH THE PAIN, EFFECTIVENESS RESEARCH NETWORK OF 2 TELEHEALTH MODEL CITIZENNA DALLASCOWBOYS.COMITYS FOR CBT, FOCUSING ON REALLY MAKING SERVICES ACCESSIBLE IN RURAL AREAS. MY CARE AS STATED THAT I'M CO LEADING WITH CATHY BRADLEY OKAYING AT OPIOID USE DISORDER AND CONCOMITANT MENTAL HEGHT AND USING A COLLABORATIVE PEER APPROACH AND PRIME AREY KACCT IRB AND BACK IN ACTION IS A STUDY I'M COLLATING WITH THOSE FOLKS. I WILL NOT FOCUS ON THOSE, YOU CAN DO THE NEXT SLIDE, BECAUSE WHEN I WAS ASKED TO GIVE THIS DAWK, I SAID THERE ARE PROBABLY PEOPLE THAT HAVE BEEN A LOT MORE IN THE TRENCHES WHERE THEY WERE RIGHT IN THE MIDDLE OF THEIR PRAGMATIC TRIALS AS COVID WAS HITTING AND HAVE A LOT TO SAY ABOUT THIS SO I WILL PULL FROM A BROADER SET OF EXPERIENCES AND FOR COLLEAGUES AND I WANTED TO POINT OUT A COUPLE OF RESOURCES THAT I SUGGEST PEOPLE LOOK AT, 1 IS THE NIH HEALTHCARE SYSTEMS COLLABRATORY AND I'VE HIGHLIGHTED HERE A TALK THAT WAS GIVEN IN THE LAST COUPLE MONTHS. I WILL COME BACK AND TALK MORE ABOUT MULTIFACTORIAL PLATFORM TRIALS AND MAYBE THE ROLE THEY PLAY IN THESE DOMAINS. THERE'S ALSO AN NIH, D.O.D. B.A, THE PAPER OUT OF THAT AND LOOKING AT WHAT'S COMING OUT OF THE PANDEMIC FOR NONPHARMACOLOGICAL TREATMENT FOR PAIN AND SUGGIEST PEOPLE LOOK AT THAT. NEXT SLIDE. SO I WILL QUICKLY TALK ABOUT 3 DOMAINS WHERE THESE PANDEMICS ESSENTIALLY HAVE COLLIDED AND ENCOURAGE US TO LOOK AT THESE ENDURING EFFECTS. FIRST REALLY WHAT ARE THE IMPACTS ON SYMPTOMS, PAIN BUT ALSO SOME OF THE WAYS IN WHICH WE CHANGE OUR BEHAVIOR AND MAY HAVE AN INSIDIOUS EFFECT ON PAIN AND SUBSTANCE USE. ENDURING CHANGE IN CLINICAL CARE AND LOOKING AT HOW THIS MIGHT CHANGE OUR CLINICAL RESEARCH APPROACH. NEXT SLIDE. SO THERE'S BEEN A LOT OF DISCUSSION, I WILL NOT BELABOR WHAT SOME OF THE IMPACTS ARE OF THE PANDEMIC ON A VARIETY OF BEHAVIORIAL HEALTH SYMPTOMS BUT IT'S BEEN QUITE PROFOUND AND I LISTED HERE, A FEW OF THE STATISTICS OF TOP ABOUT INCREASED SUBSTANCE USE, SUICIDALLITY, ANXIETY AND DEPRESSION SYMPTOMS, IN TERMS OF PAIN, THIS HAS BEEN REALLY HARD ACTUALLY TO NAIL DOWN. THERE IS A STUDY IN SPAIN THAT SUGGESTED WITH PEOPLE, THAT HAVE CHRONIC PAIN, 70% SAID THAT THEY HAD AN INCREASE IN DISABILITY PAIN RELATED INTERFERENCE AND SEVERITY. WE KNOW FROM STUDIES LOOKING AT HOW ACUTE PAIN CROSSES OVER INTO CHRONIC PAIN THAT IT'S NOT--THE STRESS HAS KIND OF A MORE MODEST ROLE AND IT REALLY IS SOME OF THE SOCIAL DETERMINANTS OF HEALTH THAT MAY HAVE A BIG IMPACT AND WE KNOW A LOT OF THOSE THINGS WERE IMPACTED, SO FINANCIAL STRESSORS IN PEOPLE, JOB RELATED STRESSORS, HOUSING, FOOD, INSECURITY, SO THOSE THINGS MAY BE PLAYING AN OUTSIDE ROLE. DAN CLAW RECENTLY DID A TOPICAL REVIEW IN PAIN CONSIDERING PROTENTIAL CHRONIC PAIN INCREASES AFTER THE COVID PANDEMIC WHICH I ENCOURAGE PEOPLE TO TACK A LOOK AT, THE OTHER THING TO KEEP IN MIND ABOUT PAIN IS THAT PEOPLE MAY BE MORE SUSCEPTIBLE TO CONTRACTING COVID. MANY ARE IMMUNE O COMPROMISED AND HAVE OTHER CO-MORBIDITIES AND THERE'S BEEN AN ENORMOUS IMPACT ON THE INTERRUPTION OF SERVICE TO RELY ON. WE ALREADY KNOW THAT THE PRESCRIBING OF OPIOIDS WAS DECREASED OVER TIME, THAT'S CONTINUED, BUT A LOT OF THE INTERVENTIONAL SERVICES LIKE INJECTIONS AND SURGERIES WERE EITHER UNAVAILABLE OR PUT OFF AND IT'S IMPACTED THE RECEIPT OF NONPHARMA CO THERAPY SERVICES AS WELL, PARTICULARLY THOSE THAT REALLY RELY ON TOUCH. WHAT I DIAGRAMMED HERE THAT I WANTED TO POINT OUT BEFORE SHIFTING GEARS HERE IS THAT WE ALSO KNOW THAT PEOPLE COPE WITH THINGS, THE BEST THEY CAN, AND MANY OF US HAVE USED LESS THAN OUR HEALTHIEST, I WILL SAY COPING STRATEGIES DURING THIS WE'VE SEEN A LOT MORE USE OF UNHEALTHY EATING AND DRUG, AND A LOT LESS INTERACTIVE AND THOSE MAY HAVE ADAPTIVE SHORT-TERM EFFECTS, PAIN, REDUCED NEGATIVE AFFECTS BUT IN THE LONG-TERM ARE QUITE MALADAPTIVE AND FOR A COLLEAGUE AT DUKE REALLY MAKE ME AWARE THAT THERE ARE ACTUALLY CAN BE REMODELING OF PAIN AND REWARD CIRCUITS THAT ARE REALLY RELATED TO THIS BEHAVIORIAL PATTERNS AND THAT IN TURN MAY REALLY EXACERBATE THESE THINGS SO THAT'S SOMETHING TO KEEP IN MIND. NEXT SLIDE. SO IN EMERGING ITS OF CLINICAL CARE, WE'VE HAD A LOT ABOUT VIRTUAL DELIVERY OF NONPHARMAICOLOGICAL TREATMENTS AND OTHER KINDS OF TREATMENTS. KISER SAID THEY HAVE COMPACTED 5 YEARS OF EXPECTED MOVEMENT TOWARDS TELEHEALTH IN AS MANY MONTHS. AND A LOT OF THOSE THINGS HAVE VERY IMPRESSIVE TECHNOLOGY DRIVEN REMOTE ISHT VENTIONS. NOW WHILE SOME OF THOSE THINGS ARE, I WOULD SAY SHALLOW AND NONTAYLORRED, I THINK THERE ARE VERY, VERY IMPRESSIVE EFFORTS WHERE YOU CAN REALLY TAYLOR THOSE THINGS AND I WILL HIGHLIGHT JUST A COUPLE. ALICIA [INDISCERNIBLE] FROM THE WEST HAVEN VA AND YALE WHO HAS 1 OF THOSE PMC COLLABRATORY PROGECS HAS A STUDY LOOKING AT 2 FORMS OF CBT AND 1 OF THEM IS DEPEND END ON INTERACTIVE VOICE RESPONSE TECHNOLOGY SO DAILY IT MAKES CALLS OUT TO PEOPLE AND HAS THEM REPORT ON 7 DEFINITE PARAMETERS, PAIN, STEPS TAKEN, SLEEP, AND A NUMBER OF OTHER THINGS. THOSE THINGS ARE COMPILED AND THEN DELIVERED BACK TO PEOPLE THROUGH THAT IBR PLATFORM WEEKLY AND THEN THAT IS USED TO REALLY REFINE THAT CBT APPROACH AND IT'S--FRAIRCHG KEITH AND OTHERS HAVE BEEN INVOLVED IN VIRTUAL REALITY PAIN TREATMENTS AND THIS GENTLEMEN HERE SHOWS THAT YOU CAN HAVE SOMETHING, WHERE YOU'RE USING SOMETHING LIKE IMAGERY BUT DOING IT IN A DEEP WAY WHERE YOU ARE--YOU CAN HAVE THE VISUALS THAT PEOPLE ASSOCIATE WITH RELAXATION, YOU COULD HAVE AUDITORY INPUT, YOU CAN HAVE WAVE MACHINES THAT PEOPLE STAND ON SO YOU MAKE IT QUITE IMMERSIVE AND THEREBY REALLY INCREASE PEOPLE'S ABILITY TO DO THAT. WE ALSO KNOW THAT THERE ARE AT LEAST TEMPORARILY LOWER REGULATORY AND PAYMENT BARRIERS TO TELEHEALTH SERVICES THAT ARE ALLOWING SERVICES TO BE CROSSED, INTERSTATE AND US TO BE ABLE TO DO THINGS MORE CENTRALLY BUT CERTAINLY OTHERS TALK ABOUT THE RISK OF EXACERBATING HEALTH INDIVIDUALS, AND BUT EVEN PEOPLE'S RELIABLE ACCESS TO TELEPHONE AND SO WE MAY NEED TO PAY FOR MINUTES, THERE ARE MEDICAID PROVISIONS THAT YOU CAN DO THAT KIND OF THING BUT WE NEED TO KEEP THAT IN MIND. I WOULD ALSO SUGGEST THERE'S A REAL HUNGER FOR FACE-TO-FACE SERVICES AND WE HEAR MANY PEOPLE SAY THAT THEY HAVE NOT HUGGED ANYBODY, THEY HAVE LIVED INDEPENDENTLY, MAYBE THEIR PET IS THE ONLY 1 THEY'VE INTERACTED WITH SO WE MAY HAVE A HINT OF DEMAND FOR TOUCH THERAPY AND THINK ABOUT THAT. NEXT SLIDE. AND I'M GOING TO END WITH THE CHANGING LANDSCAPE OF RESEARCH. THERE ARE ALL KINDS OF REALLY CREATIVE ADAPTATIONS, PEOPLE HAVE MADE IN THE SHORT-TERM BUT SOME OF THE THINGS THAT MAY BE LONGER TERM THAT ARE WORTH THINKING ABOUT ARE 3 THINGS I WILL HIGHLIGHT BRIEFLY HERE, 1 IS THE USUAL CARE IS IN CONSTANT FLUX RIGHT NOW, SO I MENTIONED WE HAVE A TELEHEALTH TRIAL COMPARING A TRAINER WHICH WE TALKED ABOUT YESTERDAY, A VERY IMPRESS OFLY INTERACTIVE SKILLS TRAINING KIND OF COGNITIVE BEHAVIORIAL BASED PROGRAM TO TELEPHONIC AND VIDEO PRESENTATION PRESENTATION AND WHAT WE FOUND IS THAT IN THE BACK DROP, MANY IN HEALTHCARE HAVE STOOD UP ONLINE KINDS OF PROGRAMS MAYBE NOT WITHIN THE STRONG EVIDENCE BASE AND THAT OFTEN TIMES ARE REALLY GREAT AT DELIVERY INFORMATION AND NOT SO GREATA REALLY HELPING PEOPLE WORK THROUGH THE BARRIERS OF LEARNING YOUR SKILLS. BUT PEOPLE FEEL LIKE THAT I HAVE ALREADY SEEN THOSE BEFORE, SO I'M CO-OPTING A TERM THAT MY COLLEAGUE TALKED ABOUT IS THAT WE NEED TO BE CAREFUL OF WEAK INOCULATIONS WHERE PEOPLE HAVE EXPOSURE TO THESE THINGS, THINK THEY'VE SEEN IT BUT HAVE NOT HAD THE SUPPORT OF WORKING 32 YOU THEM. THERE ARE ALSO A NUMBER OF ANALYTIC ISSUES THAT OVENG BROUGHT UP PARTICULARLY FOR STUDIES THAT WERE MIDTRIAL AND PATRICK KENNEDY AND OTHERS THAT ARE PART OF THE BIOSTATS CORE FOR THE NIH HEALTHCARE SYSTEMS COLLABRATORY PRISM AS PART OF THAT HAVE HELPED PEOPLE THINKING ABOUT TIME DEPENDENT CO VARIANTS TO LOOK AT NOT JUST SOMEBODY WHO WAS EXPOSED TO COVID OR CONTRACTED THE ILLNESS BUT THE PLETHORA OF IMPACTS ON PEOPLE IN TERMS OF SOME OF THOSE SOCIAL DETERMINANTS OF HEALTH AND PSYCHOLOGICALLY THAT COULD REALLY IMPACT THINGS LIKE PAIN. SO HOW WE THINK ABOUT THAT. AND THEN I WILL END WITH AN ABSOLUTELY BRILLIANT TRIAL THAT'S CONDUCTED INTERNATIONALLY CALLED REMAP CAP AND REMAP IS RANDOMIZED EMBEDDED, SO EMBEDDED IN THIS CASE, HOSPITAL SYSTEMS SO ALIGNED WITH CARE, LEVERAGING THE EHR, MULTIFACTORIAL, MEANING THAT IT'S LOOKING SIMULTANEOUSLY% AT A NUMBER OF DIFFERENT TREATMENTS AND TREATMENT REGIMES AND CAN LOOK AT SORT OF MULTIMODAL TREATMENTS IN WAYS THAT ARE QUITE MIND BOGGLES. ADAPTIVE IN THAT IT MATCHES--IT'S BUILT ON A BASIAN DECODERRIAN PROBABILITY KIND OF MODELING AND AS MORE INFORMATION COMES INTO THE SYSTEM THE RANDOMIZATION IS MATCHED BY THOSE TREATMENTS THAT ARE MORE PROMISING AND SO IT ALSO HAS A SYSTEM WHERE YOU CAN GET JUST ENOUGH PEOPLE TO ANSWER YOUR QUESTION, WHETHER IT'S 1 OF EQUIVALENCY, SUPERIORITY, INFERIORITY AND THEN GET RID OF TREATMENTS THAT ARE NOT SEEMING TO WORK AND ADD NEW THINGS TO THE PLATFORM AND THE P-IS FOR PLATFORM, YOU CAN KEEP DOING THIS RATHER THAN BELLING AN INFRASTRUCTURE RATHER THAN DISMANTLING IT FOR A SINGLE CLINICAL TRIAL. CAP IS IT WAS DEVELOPED FOR COMMUNITY ACQUIRED PNEUMONIA. THIS WAS A GROUP OF INVESTIGATORS AFTER H1N1 THAT REALIZED THEY DIDN'T HAVE THE INFRASTRUCTURE TO RESPOND QUICKLY SO THEY PUT THIS TOGETHER AND WITHIN MONTHS OF HAVING THIS PLATFORM STOOD UP, COVID ARRIVED SO THEY USE THIS AS A PLATFORM IN MORE THAN A HUNDRED--IT'S SILOED IN OUR OWN DOMAINS AND WE DON'T LOOK OUTSIDE AT THE KIND OF REALLY FABULOUS WORK THAT'S BEING DONE THAT WE MIGHT ADOPT IN OUR--FOR MAIN AND ADDICTION. I THINK IT WOULD REPLY ON THE KIND OF THING LIKE IVR TO DO REGULAR ASSESSLETS LETS--ASSESSMENTS THAT WOULD FEED INTO THIS BUT I ENCOURAGE PEOPLE TO LOOK AT THE GRAND ROUNDS THAT DERRICK ANGUS PRESENTED FROM UPMC AND IT'S A FABULOUS MODEL. SO NEXT SLIDE. FINALLY, I WILL END AND THIS IS AIAN LITTLE ORTHOGONAL TO WHAT I WAS TALKING ABOUT BUT LOOKING FORWARD, WHAT ARE THE ISSUE? S, THESE ARE THINGS THAT HAVE BEEN TALKED ABOUT. WE NEED TO REACH MORE DIVERSE POPULATIONS AND ADDRESS HEALTH INIQUITIES, WE KNOW COVID REALLY SHOWED THE INIQUITIES AND THE I AM - -IMPACT IT IS ON PAIN COULD BE QUITE SUBSTANTIAL. THERE'S MORE ATTENTION ALL THE TIME TO MULTIMORBIDITY LOOKING AT CHRONIC PAIN AND OPIOID USE DISORDER TOGETHER, EMPOWER JUST CAME OUT THAT WAS REALLY FOCUSED ON THAT, NED WILL TALK A LOT MORE ABOUT ADDICTION BUT I WILL JUST SAY THERE HAVE BEEN SEVERAL DEVELOPMENTS THAT REALLY AS RESEARCHERS AND CLINICIANS HELP US TO POTENTIALLY DO BETTER WORK IN THAT DOMAIN, TALK AGAIN ABOUT THE ELIMINATION OF X-WAIVER FOR FEW, ALTERATIONS TO CFR, SO THERE MAY BE MORE ABILITY TO LISTEN SERVICES AND I WILL SAY IN OUR NIMH SUPPORTED MY CARE, WE'RE REALLY WORRIED ABOUT THE CUTTING WITH 3 DRUGS, WELL, NOT ONLY FENTANYL AND THE EFFECT ON THE DOPA MINERGIC PATHWAYS AND WILL WE BE ABLE TO SEE SHORTER TERM DEPRESSION WHEN WE'RE TRYING TO TREAT IT. SO THERE'S ALL KINDS OF THINGS GOING ON, BOTH OPPORTUNITIES AND CHALLENGES AND THEN FINALLY, I WOULD SAY AND THIS HAS BEEN HIGHLIGHTED THAT WE REALLY NEED TO PAY ATTENTION TO THE CROWN ROYAL OF STIGMA AND HOW DOES THAT IMPACT PEOPLE AND THEIR WILLINGNESS TO SEEK CARE AND WE HAVE WONDERFUL PRESENTATIONS YESTERDAY MORNING ABOUT COMMUNITY EFFORTS AND THE HEALING COMMUNITY TO REALLY HIGHLIGHT COMMUNICATION EFFORTS IN THAT REGARD. SO THANK YOU VERY MUCH. OH AND I SHOULD SAY, THIS IS--THIS TAKES SO MANY PEOPLE AND I WANT TO RECOGNIZE THE SCIENCE INVESTIGATORS AND OUR VERY IMPORTANT PROJECT MANAGERS THROUGHOUT THESE PROJECTS THAT HAVE MADE A HUGE DIFFERENCE AND HIGHLIGHTED JUST A FEW OF THE THE PEOPLE I COLLABORATED WITH CLOSELY FROM THE NIH D.O.D. MANAGEMENT COLLABRATORY, THANKS. >> THANKS SO MUCH LYNN FOR YOUR PRESENTATION. AS YOU NOTED WE CAN'T IGNORE THE IMPACT OF HEALTH INEQUIET IS IN PAIN, AND I LOOK FORWARD TO MORE RESEARCH IN DHS AREA TO REACH DIVERSE POPULATIONS WITH INTERVENTIONS. THANK YOU. LET'S TURN TO OUR SECOND PLENARY SPEAKER DR. NED NUNES, DIRECTOR CO UMKCBIA UNIVERSITY IRVING MEDICAL CENTER, NEW YORK STATE PSYCHIATRIC INSTITUTE, THE NIDA CLINICAL TRIALS NETWORK AND CO-DIRECTOR OF THE CHOSEN CENTER AT COLUMBIA UNIVERSITY. HE'S A PRACTICING PSYCHIATRIST, BOARD CERTIFIED IN ADDICTION, PSYCHIATRY AND ADDICTION MEDICINE. HE DEVOTED HIS CAREER TO RESEARCH ON THE TREATMENT OF SUBSTANCE USE DISORDERS, AND IS BEST KNOWN FOR HIS WORK ON CO-OCCURRING DEPRESSION AND OTHER PSYCHIATRIC DISORDERS AS WELL AS COMBINED PHARMAICOLOGICAL AND BEHAVIORIAL TREATMENTS FOR SUBSTANCE USE DISORDERS, TECHNOLOGY BASED BEHAVIOR WILLIAL INTERVENTIONS AND EXTENDED RELEASE INJECTABLE OR IMPLANT FORMULATIONS OF NALTREXONE, AND BUPRENORPHINE. IN THE HEAL INITIATIVE THROUGH THE KLINEICAL TRIALS NETWORK AND THE HEALING COMMUNITY STUDY, HE'S LEADING RESEARCH ON INTERVENTION TO IMPROVE RETENTION, TREATMENT, EFFECTIVENESS AND IMPLEMENTATION OF MEDICATIONS FOR TREATMENT OF OPIOID USE DISORDER. WELCOME DR. NUNES. >> THANK YOU SO MUCH AND I APPRECIATE THE OPPORTUNITY TO BE PART OF THIS PLENARY. I WILL TALK ABOUT THE COLLISION OF COVID-19 AND THE OPIOID EPIDEMIC IN TERMS OF SUBSTANCE USE DISORDER ANDS FOCUSING SPECIFICALLYOT IMPACT RESEARCH, DESIGN AND LOGISTICS AND ALSO ON THE CONDUCT AND LOGISTICS OF TREATMENT ITSELF AND THE THEMES ARE REALLY THE WAY COVID-19 HAS DISRUPTED HOW WE DO RESEARCH AND HOW WE DO TREATMENT OF SUBSTANCE USE DISORDERS AND WHAT CAN WE LEARN FROM THAT. OKAY, NEXT SLIDE. THINKING BACK TO MARCH 2020 FOR A MINUTE, THERE WAS THIS DANGEROUS--TALKING ABOUT HALTING ALL RESEARCH THAT'S NOT SPECIFICALLY FOCUSED ON COVID-19 BECAUSE OF THE DANGERS OF THE EPIDECKIC SOPHISTICATEDY WE HAD TO THINK ABOUT HOW TO KEEP RESEARCH PARTICIPANTS SAFE AND PATIENTS SAFE. IF I COULD HAVE THE NEXT SLIDE. SO IN EMERGING ITS OF RESEARCH PARTICIPANTS, WE NEEDED TO DEVELOP WAYS OF SOCIAL AND PHYSICAL DISTANCING, WHAT ABOUT INTERVIEWS, NEUROPSYCHE TESTING, PROCEDURES, LIKE MRI, EVEN TRAVEL TO A CLINICAL CENTER FOR RESEARCH BECOMES A RISK. THE RISK OF COVID-19 ITSELF BECOMES A RISK RESEARCH PARTICIPATION. IT'S A WHOLE NEW RISK WE HAVEN'T THOUGHT ABOUT AND THEN THERE'S ALSO RISK TO THE RESEARCH PERSONNEL. NEXT SLIDE. SO WHAT WERE THE KINDS OF ADAPTATIONS? WELL AS LYNN MENTIONED ALREADY AND WE HEARD A LOT OF THAT OVER THIS WEEK, A LOT OF REMOTE AND VIRTUAL PROCEDURES BUT IN TERMS OF RESEARCH, REMOTE CONSENT WITH ELECTRONIC SIGNATURE, REMOTE ASSESSMENT WITH ZOOM OR OTHER VIDEO CONFERENCING, WEB BASED DATA COLLECTION, REMOTE NEUROPSYCHOLOGICAL TESTING, REMOTEY BIEVER HAL INTERVENTIONS WE'VE HEARD A LOT ABOUT OVER THE COURSE OF THE WEEK. USING DELIVERY TO HOMES BY FEDEX, HOME DELIVERY AND PICK UP OF BIOLOGICAL SAMPLES, URINE TESTS,A ALL THESE PRACTICAL ADAPTATIONS TO THE EPIDEMIC. NEXT SLIDE. AND IN TERMS OF IN-PERSON PROCEDURES, WE HAD TO THINK ABOUT PROTECTING STAFF AND ALL OF A SUDDEN VOLUNTEERS AND STUDENTS AND A LOT OF DIFFERENT KIND EVER RESEARCH ASSISTANTS WERE NONAPOPTOTIC THE ALLOWED TO COME ON SITE ANYMORE. IN MANY CASES THESE FOLKS ARE KIND OF GLUE THAT FOLDS RESEARCH EFFORTS TOGETHER. AND SO THAT--THAT WAS REALLY A LOSS IN ADDITION TO BEING MANDATED TO HAVE A LOWER LEVEL OF TRAFFIC AND PARTICIPANTS COMING THROUGH OUR SITES AND THEN THERE WERE QUESTIONS OF HOW TO CONDUCT OTHER PROCEDURES LIKE MRI SAFELY. IF I COULD HAVE THE NEXT SLIDE. SO WHAT HAVE WE LEARNED? FIRST OF ALL FROM THE EXAMPLE OF THE COVID-19 TRIALS AND I MUST SAY THAT I WAS STUNNED BY THE SPEED WITH WHICH THE FIELD MOUNTED TRIALS BOTH FOR THE TREATMENT OF COVID-19 AND ALSO FOR THE VACCINES AND I FOUND THIS VERY NICE PAPER BY TUTTLE WHO RUNS CLINICAL RESEARCH AT A LARGE MEDICAL CENTER SUMMARIZING WHAT THEY DID THERE BUT SOME OF THE KEY BULLET POINTS EXPEDITED PROTOCOL PREPARATION, REVIEW AND APPROVAL. ACCELERATED CONTRACTING AND BUDGETING. HOW OFTEN DO OUR EFFORTS TO MOUNT A TRIAL BOG DOWN IN CONTRACTING AND BUDGETING? FIRST PARTICIPANT ENROLLED LESS THAN 1 WEEK FROM PROTOCOL RECEIPT. THAT WAS A GOAL. THAT'S AMAZING. TO SET THAT AS A GOAL AND REALLY TRY TO SWEEP AWAY SO MANY OF THE USUAL DELAYS AND ALSO A STUDY FOR EVERY PATIENT. SO IT MAKES ME THINK ABOUT THE KIND OF PLATFORM TRIALS THAT LYNN HIGHLIGHTED. AND THEN THERE ARE A NUMBER OF ADAPTATIONS TO OUR HEAL INITIATIVE TYPES OF TRIALS FOR SUBSTANCE USE DISORDERS, REMOTE CONSENT, REMOTE MONITORING, REMOTE DELIVERY OF MEDICATIONS AND WHAT WE'RE HEARING IS THAT THESE WERE PRETTY WELL ACCEPTED BY RESEARCH STAFF. THERE'S EVIDENCE IN THE LITERATURE SURVEYS AND THINGS LIKE THAT, THAT RESEARCH STAFF LIKE THIS. NEXT SLIDE. AND SO WHAT'S--WHAT'S--WHAT DO WE KNOW ABOUT THE IMPACT OF ALL THESE CHANGES AND HOW WE DO BUSINESS ON SUBSTANCE USE DISORDERS RESEARCH AND I LOOK AT THE LITERATURE AND I FOUND A LOT OF .ARE ON HERE TEMPTING THEM , DOZENS OF .ARE ON HERE TEMPTING THEM AND ANECDOTAL REPORTS BUT LIMITED HARD DAT A. RESEARCH HAS SLOWED FOR A LOT OF TRIALS. RECRUITMENT HAS BECOME MORE DIFFICULT, AND ALSO, WHAT'S THE IMPACT OF ALL THIS REMOTE, THESE REMOTE METHODS ON ENGAGEMENT AND RETENTION. LYNN SPOKE OF THE HUNGER FOR FACE-TO-FACE CONTACT AND YOU HAVE TO WONDER HOW MUCH OF THAT FACE-TO-FACE CONTACT IS A KIND OF GLUE THAT HOLDS CLINICAL RESEARCH EFFORTS TOGETHER. BUT CERTAINLY WE ARE LEFT WITH THE BIG QUESTION, CAN THE--CAN THE ADAPTATIONS THAT WE SAW APPLY TO COVID-19 RESEARCH BE HARNESSED THE BOARD FOR HEAL AND OTHER RESEARCH? MORE EFFICIENT, CAN WE ACHIEVE MORE FLEX ELIMINATED, NIMBLE SPEEDY RESEARCH PROCESS? NEXT SLIDE, PLEASE. SO WHAT ABOUT CLINICAL PRACTICE? WHAT HAPPENED IN MARCH 2020 THERE WERE THESE SUDDEN DRAMATIC CHANGES IN THE RULES GOVERNING TREATMENT FOR SUBSIDIARY STANCE USE DISORDERS, DEA AND SAMSHA, SWIFTLY RELAXED THE RULES GOVERNING TREATMENT AND TELEHEALTH WAS FACILITATED BUPRENORPHINE WAS ALLOWED TO BE INITIATED BY TELEHEALTH WITHOUT AN IN-PERSON VISIT EXPANDED METHADONE TAKE HOMES FOR PATIENTS THAT WERE STABLE, SUDDENLY PATIENTS THAT WERE REQUIRED TO COME TO A CLINIC, 5, 6, 7, DAYS A WEEK IF THEY'RE STABLE IS GIVEN A MONTH'S SUPPLY OF METHADONE AND ONLY HAS TO COME ONCE A MONTH. AND THESE ADAPTATIONS CERTAINLY HAVE THE POTENTIAL TO MAKE MEDICATION TREATMENTS AND OTHER TREATMENTS FOR SUBSTANCE USE DISORDER MORE CONVENIENT, MORE ATTRACTIVE TO PATIENTS AND ANECDOTALLY THESE CHANGE VS BEEN WELL-ACCEPTED BY PASHTS, WELL-ACCEPTED BY PROVIDERS, [INDISCERNIBLE] A POST DOC AT COLUMBIA RAN A SURVEY OF 227 ADMINISTRATORS OR CLINICIANS AND OUTPATIENT TREATMENT OR PARM REDUCTION PROGRAMS IN NEW YORK STATE AND FOUND THAT THE MAJORITY SUPPORTED CONTINUING THESE PRACTICE AND ADAPTATIONS ALTHOUGH THERE WAS SOME VARIATION IN ACCEPTANCE AND SUPPORT WHEN YOU GET INTO IT. NEXT SLIDE. SO WHAT ARE THE OUTCOMES OF THESE PRACTICES OF ADAPTATIONS AND AND FOR THIS WE WILL WAIT FOR THE RESULTS OF THE CLINICAL RILES, THERE ARE TRIALS THAT ADDRESS THESE QUESTIONS. SOME WERE ALREADY UNDERWAY BEFORE COVID HIT, AND SOME HAVE BEEN DESIGNED AND STOOD UP DURING COVID, BUT THESE ARE JUST A COUPLE OF EXAMPLES, CLINICAL TRIALS NETWORK, TRIAL 102, RURAL EXPANSION OF MEDICATION, WHICH IS TESTING TELEMEDICINE VERSUS USUAL IN-PATIENT--IN-PERSON CARE FOR BUPRENORPHINE TREATMENT FOR OPIOID USE DISORDER. CTN-100 WILL TEST DIFFERENT SMART PHONE BASED APPS THAT WE HEARD LISA MARSH TALK ABOUT YESTERDAY, TO IMPROVE, TO LOOK AT THE IMPACT ON RETENTION AND OUTCOME OF BUPRENORPHINE AND NALTREXONE, AND THE HEAL COMMUNITY STUDY WE HEARD A LOT ABOUT. CTN112 THE OPTIMAL STUDY IS A CHART WITH THIS STUDY THAT WILL TRY TO UNDERSTAND WHETHER WHAT THE IMPACT OF THE SUDDEN CHANGES IN RELAXATION METHADONE RULES, WHAT WAS THE IMPACT OF THAT ON RETENTION, TREATMENT OF METHADONE, DRUG USE, OUTCOME AMONG METHADONE PATIENTS AND THE CONCERN ABOUT DIVERSE OF METHADONE AND THESE ARE A HANDFUL OF EXAMPLES OF TRIALS THAT WILL BE INFORMATIVE AROUND THE QUESTION OF WHAT WERE THE OUTCOMES OF THESE ADAPTATIONS AND HOW WELL DID THEY ACTUALLY WORK. AND MY LAST SLIDE, PLEASE? SO IN SUMMARY, COVID-19 AND SUBSTANCE USE DISORDERS THERE HAS BEEN ALL THIS DISRUPTION AND FROM THAT, THE ADAPTATIONS TO RESEARCH PROCEDURES AND METHODS, PARTICULARLY REMOTE PROCEDURES, IT CERTAINLY SEEMS TO MAKE--HAVE THE POTENTIAL TO MAKE RESEARCH PARTICIPATION NOR ATTRACTIVE AND CONVENIENT BUT HOW WELL DOES IT REALLY WORK AND AGAIN TO WHAT EXTENT DOES THE HUMAN TOUCH THAT LYNN TALKED ABOUT ALSO HAVE, TO WHAT EXTENT IS THAT ACTUALLY IMPORTANT TO THE RESEARCH PROCESS? AND WE HAVE OF COURSE THE EXAMPLE OF THE INCREDIBLY SWIFT CONDUCT OF COVID-19 CLINICAL TRIALS, WHAT CAN WE LEARN FROM THAT TO MAKE OUR WORK IN THE HEAL INITIATIVE FASTER AND MORE EFFICIENT. AND FINALLY, THESE MORE FLEXIBLE RULES GOVERNING TREATMENT FOR SUBSTANCE USE DISORDERS, IT BEINGLY MEDICATION, TREATMENTS BUT ALSO TELEMEDICINE, THEY HAVE A POTENTIAL TO MAKE TREATMENT MORE CONVENIENT, MORE AVAILABLE, MORE ATTRACTIVE BUT WE NEED EVIDENCE ON THEIR EFFECTIVENESS WHICH HOPEFULLY WILL SEE ROLLING OUT IN THE COMING YEARS, SO THANKS FOR YOUR ATTENTION. I APPRECIATE THE OPPORTUNITY. >> THANK YOU SO MUCH, NED. IT'S INTERESTING TO HEAR ABOUT THE ADAPTATIONS AND HOW THEY CAN MAKE SUBSTANCE USE DISORDER TREATMENT MORE ACCESS BELIEVE IN THE FUTURE. IT'S INTERESTING TO LEARN ABOUT. SO WE'RE A LITTLE BIT BEHIND SCHEDULE SO WHEY WILL ASK IS THAT WE HOLD THE QUESTIONS FOR AFTER THE PANEL AND WE WILL DO THE PLENARY SPEAKERS AND THE PANELISTS ALTOGETHER FOR QUESTIONS. SO THANKS AGAIN DR. DEBAR AND NUNES FOR SHARING YOUR INSIGHTS WITH US AND HOW THEY ADAPTED THEIR PROJECTS IN RESPONSE TO THE COVID PANDEMIC. OUR PANELISTS WILL PROVIDE ADDITIONAL REFLIKSS ON LESSONS LEARNED OVER THE PAST 14 MONTHS UNDER THE COLLIDING COVID-19 AND PAIN AND OVERDOSE CRISIS. SO I FIRST WANT TO INTRODUCE THE MODERATOR FOR THE SESSION, DR. FRANCIS O'OKEEFE, HE IS PROCESSOR AND DIRECTOR OF THE DUKE UNTIL CENTER'S PAIN PREVENTION AND TREATMENT RESEARCH PROGRAM. HE'S PUBLISHED OVER 450 ARTICLES ON PAIN AND PAIN MANAGEMENT. HE'S EDITOR IN CHIEF OF PAIN, THE PREMIER JOURNAL DEVOTED TO PUBLISHING BASIC AND APPLIED PAIN RESEARCH AND I'LL NOW INTRODUCE THE DISTINGUISHED PANELISTS, DR. SHARON WALSH IS A PROFESSOR OF BEHAVIORIAL SCIENCE, PSYCHIATRY, PHARMAICOLOGY AND PHARMA SUITICAL SCIENCES AND THE DIRECTOR OF THE CENTER ON DRUG AND ALCOHOL RESEARCH AT THE SHE'S CONDUCTED NIH FUND TD RESEARCH ON OPIOID USE DISORDER AND TREATMENT FOR SEVERAL DECADES IS THE PRINCIPAL INVESTIGATOR ON THE KENTUCY HEALING COMMUNITY STUDY. DR. FAYE TAX-MAN IS A UNIVERSITY PROFESSOR IN THE SCAR, SCHOOL OF POLICY AND GOVERNMENT AND DIRECTOR OF THE CENTER FOR ADVANCING CORRECTIONAL EXCELLENCE AT GEORGE MASON UNIVERSITY. SHE'S A HEALTH SERVICES CRIMINOLOGYST AND HAS CONDUCTED NIH AND DEPARTMENT OF JUSTICE FUNDED STUDIES ON CRIMINALLY INVOLVED POPULATIONS FOR OVER 3 DECADES. SHE'S PI FOR THE JCOIN ACCORD NATION AND TRANSLATION CENTER. DR. KEVIN VOWLES, CURRENTLY HOLDS A CHAIR AS PROFESSOR OF CLINICAL HEALTH PSYCHOLOGY IN THE SCHOOL OF PSYCHOLOGY AT QUEEN'S UNIVERSITY BELFAST. HIS CLINICAL AND ACADEMIC WORK HAS FOCUSED ON THE ASSESSMENT AND EFFECTIVE REHABILITATION OFFED HAVES WITH CHRONIC PAIN. HE'S PUBLISHED OVER A 110 SCIENTIFIC ARTICLES AND THESE AREAS, WITH RECENT WORK CONCENTRATING ON IDENTIFYING THE CHARACTERISTICS OF EFFECTIVE TREATMENT AND DIFFERENTIATING PROBLEMATIC FROM NONPROBLEMATTIC OPIOID AND ALCOHOL USE IN THOSE WITH CHRONIC PAIN. AND DR. ELIZABETH D'AMICO AND A BEHAVIORIAL SCIENTIST AT THE RANDOMIZED TRIAL CORPORATION AND A LICENSED CLINICAL PSYCHOLOGIST. SHE'S NATIONALLY RECOGNIZED FOR HER WORK DEVELOPING, IMPLEMENTING AND EVALUATING INTERVENTIONS FOR ADOLESCENTS AND YOUNG ADULTS. SHE HAS SEVERAL GRANTS FOCUSED ON PREVENTION OF ALCOHOL AND DRUG USE FOR URBAN NATIVE AMERICAN ADOLESCENTS AND YOUNG ADULTS THAT INTEGRATE MOTIVATIONAL INTERVIEWING WITH TRADITIONAL PRACTICES SUCH AS UPON EATING AND NATIVE AMERICAN COOKING. CLEARLY AN IMPRESSIVE GROUP DOING IMPORTANT WORK AND I KNOW OUR ATTENDEES ARE EXCITED TO HEAR FROM YOU ALL SO LET'S GET RIGHT TO IT AND I WILL TURN THE FLOOR OVER TO DR. O'KEEFE, AND TH PANELISTS,. >> SURE, WILL HAVE BRIEF PRESENTATIONS BY EACH OF THE PANELISTS AND THEN WE WILL OPEN IT UP FOR DIS DISCUSSIONS AND QUESTIONS. >> SO WITHOUT FURTHER ADO, SHARON COULD YOU LEAD US OFF? >> SURE. MY PURPOSE IS TO GIVE YOU AN OVERVIEW OF THE HEALING COMMUNITY STUDIES SO YOU'RE ORIENTED FOR THE DISCUSSION, BUT IF YOU'VE BEEN PARTICIPATE NOTHING IN MEETING, YOU HAVE HEARD THIS IN 2 DAYS PRECEDING THIS BECAUSE WE HAD SPEAKERS TALKING ABOUT THIS STUDY. SO CAN YOU GO TO THE NEXT SLIDE. JUST VERY BRIEFLY, HEALING COMMUNITY STUDY IS A 5 YEAR MULTISITE PARALLEL GROUP CLUSTER RANDOMIZED WEIGHT LIST CONTROLLED STUDY WITH A TOTE AFRONS OF 67 COMMUNITIES THAT WERE HIGHLY IMPACTED BY THE OPIOID OVERDOSE CRISIS, IT'S A MIX OF URBAN AND RURAL COMMUNITIES AND COVERS A POPULATION OF OVER 10 MILLION PEOPLE. CAN YOU SEE THAT THE STATES THAT ARE PARTICIPATING ARE NEW YORK, OHIO, MASSACHUSETTS AND KENTUCKY AND THE OBJECTIVE IS TO REDUCE OPIOID DEATHS THROUGH A COMMUNITY ENGAGED AND IMPLEMENTATION SCIENCE BASED EXPANSION OF EVIDENCE-BASED PRACTICES ACROSS MULTIPLE SECTORS INCLUDING BELGT'RE HEALTHCARE, BEHAVIORIAL HEALTH, CRIMINAL JUSTICE TO REACH VULNERABLE POPULATIONS. THE TIMELINE IS SHOWN ON THE FIGURE IN THE BOTTOM, AND SO RIGHT NOW JUST TO ORIENT YOU, WE ARE IN THE MIDDLE OF THE INTERVENTION WITH OUR WAVE 1 COMMUNITIES. THOSE ARE THE 1S THAT WERE RANDOMIZED TO GO FIRST AND I CAN SAY THAT WE DEFINITELY FELT THE IMPACT OF COVID. NEXT SLIDE. AND THEN JUST TO REMIND YOU ABOUT THE INTERVENTION ITSELF, THE INTERVENTION IS CALLED COMMUNITIES THAT HEAL INTERVENTION. THESE LEAD THE COMMUNITIES TO RECOGNIZE WHAT THEIR STRENGTHS AND WEAKNESSES ARE AND WHAT THE GAPS ARE AND WHAT IS NEEDED REALLY TO FILL THOSE GAPS AS FAR AS IMPLEMENTING EVIDENCE-BASED PRACTICES THAT WILL REDUCE OPIOID OVERDOSE DEATHS. WE ALSO HAVE A PUBLIC HEALTH COMMUNICATIONS CAMPAIGN THAT'S MEANT TO DRIVE DEMAND IN DECREASED STIGMA AND YOU HEARD ABOUT THAT ARE FROM JENNIFER REYNOLDS YESTERDAY AND THE THIRD PART TELEVISION IS EVIDENT-BASED STRATEGIES THAT ARE IMPLEMENTED THROUGH IMPLEMENTATION SCIENCE, WORKING WITH AGENCIES AND COMMUNITIES AND AND THE 3 GENERAL CATEGORIES OF EVIDENCE-BASED PRACTICES ARE INCREASING OPIOID OVERDOSE EDUCATION AND NALOXNE DISTRIBUTION AND ENHANCING DISTRIBUTION OF MEDICATIONS FORROID USE DISORDER AND FINALLY IMPROVING PRESCRIPTION OPIOID SAFETY. AND THAT'S IT. >> THANK YOU. OUR NEXT SPEAKER IS FAYE, AND COULD YOU SUMMARIZE YOUR PROJECT? >> THANK YOU. I AM ALSO TALKING ON BEHALF OF THE JUSTICE COMMUNITY OPIOID INNOVATION NETWORK, JCOIN WHICH IS FUNDED UNDER THE HEAL INITIATIVE TO REALLY FOCUS ON A VERY LARGE POPULATION IN THE U.S. THAT HAS A HIGHER RATE OF [INDISCERNIBLE] DISORDER AND MENTAL HEALTH DISORDERS. NEXT SLIDE, PLEASE. SO FOR THOSE WHO ARE UNAWARE, ABOUT 20% OF THE AMERICAN ADULT POPULATION IN THE UNITED STATES HAS HAD SOME INVOLVEMENT WITH THE CRIMINAL JUSTICE SYSTEM DIRECTLY BUT THAT ALSO MEANS THAT THERE ARE FAMILIES, CHILDREN, WHO ARE ALSO INVOLVED AND FROM THIS BUSINESS THIS IS A NEED--CARE AND QUALITY OF--LARGE VISION THAT'S TRANSFORMATIVE ABOUT THE ROLE OF PROVIDING CARE TO PEOPLE WHO WERE INVOLVED IN THE JUSTICE SYSTEM. AND SO WE IDENTIFIED A VISION THAT'S REALLY ABOUT USING THE JUSTICE SYSTEM AS A MEANS TO PROVIDE EFFECTIVE TREATMENT JCOIN AS A COOPERATIVE ACTUALLY HAS A LOT OF DIFFERENT COMPONENTS TO IT. MAINLY COMPONENTS RELATED TO RESEARCH DEVELOPING COLLABORATIVE NETWORKS THAT WILL FACILITATE ACCESS SERVICES AND QUALITY SERVICES, ENGAGING THE STAKEHOLDER COMMUNITY AND DISSEMINATION FOR THE PURPOSE OF TRANSFORMING THE FIELD AND ALSO, YOU KNOW TRAINING OUR NEXT GENERATION OF RESEARCHERS AND PRACTITIONERS AS PARLIAMENT OF A REVISED ENTERPRISE FOR THE JUSTICE SYSTEM. SO AS PART OF JCOIN, THERE ARE 13 CLINICAL TRIALS MANY OF THOSE HAVE TO DO WITH INCREASINGK SESES AND RETENTION IN MEDICATIONS FOR OPIOID USE DISORDERS, MANY USING PEER NAVIGATORSAs A MEANS ALSO TO IMRIEWF ACCESS AND PILOTING AND TESTING NEW IDEAS ABOUT HOW TO TRANSFORM THE JUSTICE SYSTEM YOU CAN SEE HERE THAT THE REACH IS VERY LARGE IN TERMS OF THE PROJECTS. WE HAVE 37 STATES. WE HAVE, YOU KNOW OVER SEIVET THOUSAND INDIVIDUALS WHO ARE INVOLVED IN JCOIN RELATED EFFORTS TO ENGAGE STAKEHOLDER SYSTEM REALLY AROUND NOT ONLY OUR RESEARCH PARTNER, EACH OF THE JCOIN RESEARCH TEAMS HAD TO BRING ON AT LEAST 5 PARTNER AGENCIES, 5 COMMUNITIES, SORRY THAT INCLUDED HEALTH AND JUSTICE PARTNERS AND BUT MORE SO THE JCOIN CTC WHICH I AM RESPONSIBLE FOR, WE ARE ENGAGING THE STAKEHOLDERS ACROSS 67 DIFFERENT LANES, IN TERMS OF WAYS TO FACILITATE SUSTAINED CHANGE. AND SO THE ENTERPRISE IS REALLY DESIGNED AROUND A DIFFERENT VISION WHERE THE JUSTICE SYSTEM--I'M NOT GOING TO GO INTO THIS BUT OUR RESEARCHERS HAVE BEEN EXTREMELY ACTIVE IN, DATA PROTECTIONING TO COVID. MANY, YOU HEARD ED NUNES BEFORE US TALK ABOUT THE ADAPTATIONS THAT HAVE OCCURRED. MANY OF THOSE ADAPTATIONS IN THE JCOIN INITIATIVE HAVE INCLUDED IN THE INTERVENTION ASPECTS, CHANGING HOW THE INTERVENTIONS WERE GOING TO ACTUALLY BE DELIVERED USING TELEHEALTH, ZOOM ROOMS, MOBILE VANS AND THEN WE HAVE ENHANCED DATA COLLECTION PROCEDURES, THAT ARE REALLY DESIGNED AROUND USING AGAIN TELEHEALTH PLATFORMS FOR ALL PHASES OF RESEARCH AND FINALLY REACH, WE HAVE FOUND THAT THE COLLABORATIVE PROCESS, THAT INVOLVES STAY HOLDERS AT THE LOCAL LEVEL HAVE FACILITATED THE CONTINUATION OF RESEARCH REGARDLESS OF WHETHER WE'RE IN A COVID PANDEMIC STATE OR NOT. SO THESE ARE LONG LASTING SUSTAINABLE EFFORTS AND YOU KNOW WE HAVE ALSO FOUND THAT THROUGH THE MECHANISMS THAT WE'RE USING, THAT WE'RE ABLE TO ACTUALLY ENGAGE STAKEHOLDERS IN A WAY IN WHICH THEY FEEL VERY CONNECTED TO THINKING ABOUT HOW TO ACTUALLY DO THIS TRANSFORMATIVE WORK. SO WITH THAT I WILL STOP BECAUSE WE'RE GOING TO GET IN HAD MORE DETAILS ABOUT THE COVID ADAPTATIONS BUT I JUST WANTED TO GIVE YOU A QUICK OVERVIEW AND ALSO TO EMPHASIZE HOW IMPORTANT IT IS FOR THIS PARTICULAR POPULATION JUST BECAUSE OF THE PREVALENCE OF THOSE SUBSTANCE USE DISORDERS, PAIN, ELATION AND THE NEED TO REALLY TRANSFORM A SETTING IN WHICH ITS ILL PREPARED TO PROVIDE EVIDENCE-BASED TREATMENTS. >> I'M GETTING A LITTLE INTERFERENCE SO IF ANYBODY THAT'S SHOWING UP ON THE SCREEN HAS NOT MUTED YOUR MIC, IF YOU COULD DO THAT ISSUES THAT WOULD BE GREAT. OUR NEXT SPEAKER IS KEVIN, DO YOU WANT TO TAKE CHARGE NOW? >> SURE. THANK YOU VERY MUCH, FRANK FOR THE INTRODUCTION AND THANKS FOR THE INVITATION TO BE HERE TODAY. I AM KEVIN VOWLES, I AM 1 OF 2 PIs FOR A STUDY I WILL BRIEFLY DESCRIBE HERE, THE OTHER PI IS PROFESSOR KATIE WITKIEWITZ. THIS STUDY IS CALLED THE PAIN AND OPIOID INTEGRATED TREATMENT IN VETERANS OR POSITIVE STUDY AND IN ESSENCE WHAT WE ARE SEEKING TO DO IN THIS STUDY IS EXAMINE THE EFFICACY OF AN INTEGRATED BEHAVIORIAL TREATMENT THAT SEEKS TO REDUCE CHRONIC PAIN RELATED INTERFERENCE AND OPIOID MISUSE IN VETERANS WITH CHRONIC PAIN AND IN AN OPIOID USE DISORDER, NEXT SLIDE, PLEASE. AND WHOEVER IS ADVANCING THE SLIDE, I HAVE A FEW LINES IN HERE SEQUENT QUALLY SO IF YOU HIT RETURN 4 TIMES, I THINK THAT WILL BRING UP ALL MY INFORMATION. THANK YOU VERY MUCH. GIVEN THAT WE'VE BEEN ASKED TO BRIEFLY DESCRIBE THIS STUDY, I THOUGHT I WOULD PROVIDE JUST A BIT BRIEF BACKGROUND SPECIFIC TO CHRONIC PAIN, OPIOIDS AND VETERANS AND WHAT WE KNOW IS THAT CHRONIC PAIN IS COMMON, NUMBER OF LARGE SCALE WELL DESIGNED STUDIES IS ARE INDICATE THAT SOMEWHERE TBEEN 20 AND 25% OF ADULTS IN THE WORLD WE KNOW THE EXPERIENCE OF CHRONIC PAIN IS ASSOCIATE WIDE SUBSTANTIAL DIRECT ASK INDIRECT HEALTHCARE COSTS AND THAT CHRONIC PAIN IS RELIABLY ASSOCIATED WITH CLINICALLY SIGNIFICANT LEVELS OF DISTRESS AND DISABILITY. EVERYONE WHO'S AT THIS MEETING WILL KNOW THAT PRESCRIPTION RATES INCREASED SUBSTANTIALLY OVER THE PAST FEW DECADES AND THAT CO INSIDED WITH SUBSTANCIAL INCREASES IN OPIOID RELATED MORBIDITY AND MORTALITY. IN THE AREA OF CHRONIC PAIN WHERE MANY PEOPLE WITH CHRONIC PAIN WERE HISTORICALLY PRESCRIBED OPIOID AS PART OF THEIR TREATMENT REGIMEN WHAT WE HAVE SEEN OVER THE PAST FEW DECADES IS AN INCREASE OF HAZARDOUS OPIOID USE OR THAT WE'RE MORE AWARE OF HAZARDOUS OPIOID USE AS WE'VE BEEN ASSESSING FOR IT MORE FREQUENTLY. NOW AS I NOTED THIS IS A STUDY IN VETERANS AND WHAT THE EVIDENCE SUGJUDGEST SYSTEM THAT THESE PROBLEMS OF RON CHRONIC PAIN BEING CONSTANTLY BILLITATING INCREASING SUBSTANTIALLY THAT THESE PROBLEMS ARE MORE PRONOUNCED IN VETERANS IN THE U.S. UP TO 2/3RDS OF VETERANS HAVE CHRONIC PAIN, HALF OF THOSE HISTORICALLY RECEIVE AN OPIOID PRESCRIPTION AND HALF OF THOSE HAVE RECEIVED OPIOID DOSES, PRESCRIPTION DOSES THAT ARE WELL IN EXCESS OF RECOMMENDED GUIDE LINES FOR MAXIMUM DOSE. IN A PRAGMATIC CLINICAL PROBLEM IS SUMMARIZED TO OFFER INTEGRATED INTERVENTION OR PAIN RELATED INTERFERENCE AND POIGN-RELATED OPIOID USE. AND THAT'S WHAT THE TRIAL SEEKS TO EXAMINE IN A FULLY POWERED 2 ARM EFFICACY STUDY. THIS WORK BUILDS ON A PREVIOUS CLINICAL PILOT STUDY OF OURS THAT WAS FUNDED BY NCCIH WHICH SUGGESTED THIS INTEGRATED INTERVENTION IS FEASIBLE, ACCEPTABLE AND HAD SOME EVIDENCE OF EFFECT IN RELATION TO TREATMENT AS USUAL. SO THE LAST LINE OF THIS SLIDE IBDICATE THIS IS IS A 2 ARM STUDY, OUR INTEGRATED INTERVENTION IN COMPARISON TO AN ACTIVE EDUCATION CONTROL CONDITION, EDUCATION CONTROL CONSISTS OF PAIN NEUROSCIENCE EDUCATION, AS WELL AS OPIOID SAFETY AND USE EDUCATION, IT'S A TRUE SITE STUDY, COMING ACROSS 2 VA HEALTHCARE SYSTEMS, PIEWJET SOUND AND NEW MEXICO AND WE ARE PLANNING TO FOLLOW THIS UP THROUGH A PERIOD OF 1 YEAR. NEXT SLIDE. AND FRANK, I'M ALMOST DONE BECAUSE I KNOW YOU ARE TIME KEEPER AND KEEPING TRACK OF EVERYTHING. WE HAVE BEEN READY TO BEGIN TO RECRUIT FOR THIS STUDY FOR SEVERAL MONTHS BUT OF COURSE THERE HAVE BEEN COVID RELATED DELAYS, 1 SUBSTANTIAL PROSPECT PROBLEM THAT WE FACE IS THAT OUR INTERVENTION WAS INTENDED TO BE CONDUCT INDEED A GROUP FORMAT IN PERSON, WE HAVE SEVERAL BEAUTIFUL ADVERTISEMENTS AND RECRUITMENTS, FLYERS WHICH ARE ON YOUR SCREEN RIGHT NOW, BUT AWZ OF THE COVID RELATED DELAYS WE HAVE ALTERED THE STUDY IN SOME WAYS. NEXT SLIDE, PLEASE. AND THOSE SLIDES SPECIFICALLY ARE TO ADD-ON FEASIBILITY AND ACCEPTABILITY STUDY TO THE PARENT TRIAL TO DETERMINE WHETHER OR NOT TELEHEALTH INTERVENTION IS FEASIBLE AND ACCEPTABLE. BECAUSE OF THE DELAYS WE HAD THAT WERE NOUGHT ABOUT A YEAR AND A HALF INTO THIS GRANT AND A LITTLE BIT OF BUDGET LEFT OVER DISP WHAT WE HAVE DONE HAS GOTTEN IRB APPROVAL FOR TELEHEALTH STUDY, THE PRIMARY AIMS OF THIS STUDY ARE FEASIBILITY AND ACCEPTABILITY. WE PLAN TO RUN 1 GROUP, WOKNOW CONTROL GROUP, 1 TREATMENT GROUP AT EACH OF OUR 2 SITES SO 4 GROUPS IN TOTAL TO RECRUIT A TOTAL N-40 TO EXAMINE THESE ISSUES. NEXT SLIDE, PLEASE. THAT'S IT FOR ME. THANK YOU VERY MUCH FOR YOUR ATTENTION. >> THANK YOU VERY MUCH. OUR FINAL PANELIST IS LIZ D'AMICO, IF YOU COULD GO AHEAD. LIZ, CAN YOU HEAR ME. >> SORRY, YSES, HAVING INTERNET ISSUE, CAN YOU HEAR ME NOW? NWE CAN, THANKS. >> GREAT. SO I'M HERE TODAY TO TALK TO YOU ABOUT TACUNA WHICH IS TRADITIONS AND CONNECTIONS FOR URBAN NATIVE AMERICANS. AS WAS NOTED EARLIER I'M A CLINICAL PSYCHOLOGIST AND I'M PART OF THE MOTIVATIONAL INTERVIEWING NETWORK OF TRAINERS AND I'M PI ON THIS PROJECT WITH DR. DAN DICKERSON WHO'S AN ALASKA NATIVE INVESTIGATOR WHOSE KNOWN FOR INTEGRATING TRADITIONAL PRACTICES TO TREAT SUBSTANCE USE PROBLEMS. NEXT SLIDE, PLEASE. IN TERMS OF OUR INTERVENTION, IT'S A RANDOMIZED CONTROL TRIAL WITH 3 SEIVET AMERICAN INDIAN AND ALASKA NATIVE ADULTS WHO LIVE IN URBAN CITIES. WHAT'S IMPORTANT ABOUT THIS TRIAL IS THAT ALL PEOPLE RECEIVE CULTURALLY APPROPRIATE TREATMENT. HALF RECEIVE TACUNA PLUS A WELLNESS GATHERING AND THAT I WILL EXPLAIN IN A MINUTE AND HALF RECEIVE A CULTURALLY SENSITIVE OPIOID EDUCATION WORKSHOP AND THEN WE,A SESES OUTCOMES OVER A YEAR. WHAT WE'VE DONE WITH TACUNA IS CREATE 3 WORKSHOPS BASED ON OUR PREVIOUS WORK WITH THIS POPULATION AND WE'VE INTEGRATED MI WITH TRADITIONAL HEALING PRACTICES, SUCH AS DISCUSSING CULTURAL IDENTITY, NATIVE COOKING AND PRAYER AND BURNING SAGE. AND WE ALSO TALK ABOUT SOCIAL NETWORK INFLUENCES, INFLUENCES THAT MAYBE PUT US AT RISK FOR SUBSTANCE USE, INFLUENCES THAT CAN HELP PROTECT US FOR EXAMPLE BY ENGAGE NOTHING TRADITIONAL PRACTICES. NEXT SLIDE, PLEASE. AS MANY OF THE PROJECTS DISCUSSED WE'VE HAD TO MAKE ALLOT OF ADJUSTMENTS DUE TO COVID-19 PANDEMIC, THE MAIN ASHES JUSTMENT AS MANY PROJECTS HAD TO DO WAS VIRTUAL IMPLEMENTATION. SO WE WERE SUPPOSED TO BE IN-PERSON GROUPS IF ARE THIS SPECIAL WE NOW MOVED TO VIRTUAL AND IT TOOK MORE PLANNING WITH THE PLATFORM, WE HAD TO PILOT TEST IT BUT WE DID FIND IN TERMS OF FEASIBILITY THAT IT WAS INCREASED CONVENIENCE FOR PARTICIPANTS AND THEY ACTUALLY PREFERRED BEING IN THEIR HOME. IT LOWERS SOME OF OUR TRANSPORTATION COSTS SO INSTEAD OF HAVING TO PAY FOR PEOPLE TO COME TO THE GROUPS, WHAT WE NOW DO IS MAIL ALL OF OUR WORKSHOPPA--THEY GET ALL THEIR COOKING INGREDIENTS, THEY GET THEIR SAGE AND THEN WE USE THE COOKING INGREDIENTS TOGETHER AND COOK VIRTUALLY AND IT'S ACTUALLY WORKED REALLY WELL. WE HAD TO CHANGE OUR RECRUITMENT PROCEDURES AND EVERYTHING WENT TO ONLINE RECRUITMENT AND THAT ACTUALLY HAS GONE REALLY WELL. DAN AND I EXPECTED APPROXIMATELY 12 PEOPLE PER MONTH AND AFTER OUR SOCIAL MEDIA ADVERTISING WE GOT 146 PARTICIPANTS IN A WEEK. SO IT'S BEEN GOING VERY WELL. WE'VE CONDUCTED 45 WORKSHOPS SO FAR AND THE PARTICIPANTS ARE ACTUALLY REALLY ENJOYING THE VIRTUAL EXPERIENCE BEING ABLE TO MEET OTHER NATIVE AMERICAN YOUNG ADULTS EERVE THOUGH IT'S VIRTUALLY AND BEING ABLE TO PARTICIPATE IN THESE TRADITIONAL PRACTICES TOGETHER. THANK YOU. THANK YOU VERY MUCH LIZ AND I WOULD LIKE TO THANK EVERYONE FOR THE FORMAT AND THE SPEAKERS FOR THEIR BRIEF PRESENATIONS, THEY CLEARLY COULD HAVE TALKED A LOT MORE BUT AS A GROUP WE THOUGHT IT WOULD BE BEST TO DEVOTE THIS TIME AS MUCH AS POSSIBLE TO INTERACTION WITH THE AUDIENCE BECAUSE WE KNOW THAT EACH OF YOU ARE INVOLVED IN PROJECTS WHERE YOU HAVE HAD TO MAKE ADAPTATIONS AND THERE ARE PROBABLY VERY INTERESTING LESSONS LEARNED AND THEMES THAT HAVE COME OUT, CUT ACROSS PROJECTS AND EVEN WITHIN PROJECTS THAT NEED TO BE RAISED AND DISCUSSED AS A GROUP. SO I WOULD LIKE ALL THE PRESENTERS AS WELL AS THE PANELISTS, WE WANT TO INVOLVE THE PANELISTS TO TURN ON YOUR VIDEO AND MAYBE ADDRESSING FIRST OF ALL QUESTIONS THAT ARE RAISED IN THE CHAT. SO I WOULD ENCOURAGE YOU IF YOU'RE A MEMBER OF THE AUDIENCE TO--IF YOU DO HAVE A QUESTION, WE ALREADY HAVE A COUPLE. WE WILL PRIORITIZE THOSE QUESTIONS FROM THE AUDIENCE AND THEN GO TO SOME PREPARED QUESTIONS THAT WE PULLED TOGETHER THAT WILL HIGHLIGHT SOME OF THESE THEMES. SO WITHOUT FURTHER ADO, AND I HAD MENTION FOR THE SPEAKERS IF YOU ARE--IF YOU HAVE A GOOD RESPONSE AND YOU WANT TO RESPOND TO 1 OF THE POINTS, PLEASE RAISE YOUR HAND AND I WILL BE SURE THAT YOU GET A CHANCE TO GO AHEAD AND OPT INTO THAT PARTICULAR DISCUSSION. THE FIRST QUESTION IS A VERY INTERESTING 1 FROM MEGAN MURPHY, SHE'S SAYS, 1 OF THE MAJOR ISSUES DURING COVID HAS BEEN GETTING INTERNET ACCESS TO COMMUNITIES THAT TYPICALLY HAVE POOR OR NO INTERNET INFRASTRUCTURE. SHE MENTIONED RURAL COMMUNITIES WE'VE HEARD ABOUT OTHER COMMUNITIES IN PRESENTATIONS, TODAY. SO, COVID CERTAINLY HAS BROUGHT ATTENTION TO THE LACK OF ACCESS TO THESE RESOURCES. AND SO SOME OF THE OTHER AKACCT TININE PATHWAYATIONS MAY ULTIMATELY LEAD TO MORE CAPACITY TO DELIVER HEALTH SERVICES PARTICULARLY THOSE THAT ARE REMOTELY DELIVERED. AND I THOUGHT I WOULD THROW THIS TO SHARON SIN SHE WORKS WITH COMMUNITIES FOR FIRST RESPONSE AND THEN MAYBE FAYE, YOU COULD FOLLOW UP ON IT. >> THANK YOU, FRANK. THIS IS A MULTIPRONGED QUESTION WITH RESPECT TO THE ACTUAL TECHNOLOGICAL SUPPORT. IN THE HEALING STUDY THERE WAS KIND OF A SPEEDY MOVE IN SOME COMMUNITIES TO DEVELOP HOT SPOTS THAT COULD BE USED WHEN BROAD BAND ACCESS WAS LESS AVAILABLE. EVEN ACCESS TO PHONE SERVICES RELIABLE CELL SERVICES ESPECIALLY IN RURAL AREAS CAN BE REALLY PROBLEMATIC AND SO, IN MASSACHUSETTS WHEN THEY WERE WORKING WITH [INDISCERNIBLE] EARLY ON IN THE PANDEMIC 1 OF THE THINGS THAT THEY SAID WAS A GREAT NEED WAS ACTUALLY JUST TO HAVE SOME ADDITIONAL CELL PHONES THAT COULD BE USED FOR PATIENT CONNECTION. IN OHIO 1 OF THE THINGS THEY WORKED ON WAS REIMBURSEMENT FOR MINUTES WHICH HADN'T BEEN AVAILABLE BEFORE TO ALLOW FOR ONGOING SERVICES. IN SOME CASES WE ACTUALLY HAD TO DO PROVIDE TECHNICAL ASSISTANCE TO THE COMMUNITIES AND THE COALITIONS BECAUSE THEY WERE THE LISTEN TO THE REST OF THE COMMUNITY TO INSURE ONGOING ACCESS TO TRANSFER OF INFORMATION AND THEN THE OTHER WAY THAT WE REALLY LEVERAGED IT WAS WE MOVED A LOT OF RECOVERY SO WE STARTED NEW MEETINGS WHERE THEY DIDN'T EXIST BEFORE AND WE NEEDED TO LEVERAGE THE INTERNET IN ORDER TO DO THAT. AND SO IN CASES WHERE THERE WERE RECOVERY PROGRAMS, WHERE THERE'S ACTUALLY LIKE A BRICKS AND MORTAR PLACE PEOPLE COULD GO AND USE THE INTERNET THERE TO JOIN TO A MEETING IN ANOTHER COMMUNITY. SO THERE WAS A LOT OF PIVOTING AROUND THIS AND THE WAY THAT LOOKED DIFFERENT IN EACH COMMUNITY, YOU KNOW DEPENDING ON THEIR LOCATION AND NEEDS. >> THANKS, SHARON SO IT SOUNDS LIKE YOU WOULD CONCLUDE THAT YES, THIS MAY INCREASE ACCESS, ALL THESE TYPES OF ADAPTATIONS COULD INCREASE ACCESS DOWN THE LINE, SO LET ME GET FAYE TO WEIGH IN BECAUSE I KNOW YOU ALSO WORK WITH POPULATIONS WHERE ACCESS HAS BEEN AN ISSUE. >> RIGHT. THANK YOU. SO I DON'T WANT TO REPEAT ALL OF THE MECHANISMS THAT PEOPLE USE TO BE ADAPTIVE DURING COVID THAT SHARON RAISED BECAUSE MANY OF THOSE APPLIED TO THE STUDIES THAT ARE CONDUCTED AS PART OF JJOIN JCOIN BUT WHAT'S MORE IN OUR PERSPECTIVE BECAUSE WE'RE IN TYPICAL SETTINGS, JAILS, COURTHOUSES, YOU KNOW PROBATION OFFICES, SOME OF THE THINGS THAT APPEAR IS THAT THE TELEHEALTH WHICH WASN'T REALLY RECOGNIZED AS A WAY OF DELIVERING SERVICES SEEMS TO HAVE FOUND ACCEPTABILITY VERY MUCH SO BY JUSTICE ACTORS. AS A MEANS BY WHICH PEOPLE COULD ACTUALLY ONLY GET ACCESS TO CARE. AND 1 OF OUR MEETINGS WE HAVE A JUDGE WHO TOLD US THAT HE WAS ABSOLUTELY AMAZED HOW MUCH MORE RELAXED CLIENTS WERE HAVING COURT HEARINGS VIA TELECOMMUNICATIONS AS COMPARED TO IN-PERSON. AND THAT IT REDUCED STRESS OF CLIENTS TO A DEGREE THAT HE COULD REALLY RECOGNIZE THAT. AND I THINK THAT, YOU KNOW SUGGESTS THAT SOME OF THE BURDENS THAT OUR POPULATIONS EXPERIENCE GETTING THE PLACES, RIGHT? THE TRANSPORTATION, MAKING ARRANGEMENTS, ALSO THE SETTINGS THEMSELVES BECAUSE, YOU KNOW IF YOU'VE BEEN IN A JAIL OR IN A COURTHOUSE OR MANY PROBATION AGENCIES, THEY'RE NOT THE MOST WELCOMING PLACES TO BE AND YET, YOU KNOW THE TELEHEALTH SORT OF ADAPTATIONS HAS PROVIDED A NEW INFRASTRUCTURE FOR COURTS AND OTHER JAILS TO REALLY CONSIDER WAYS IN WHICH TO ENGAGE KIENTS AND TO MAKE IT MORE ACCESSIBLE FOR CLIENTS. SO THAT'S 1 ASPECT THAT I THINK IS REALLY INTERESTING IS THAT, YOU KNOW THE ADAPTATION, NOW OF COURSE COMES WITH THAT, IS AS, YOU KNOW AS SHARON INDICATED, A LOT OF OUR PATIENTS IN THE JUSTICE SETTINGS DO NOT HAVE ACCESS TO CELL PHONES THAT HAVE CAPABILITIES LIKE IPHONES OR ANDROIDS, THEY HAVE OLD STYLE PHONES OR MEDICAID ELIGIBILITY PHONES AND THEREFORE THERE HAS BEEN A NEED TO REALLY PROVIDE ACCESS TO IPADS AND DIFFERENT TYPES OF CELL PHONES FOR CLIENTS SO THEY COULD ACTUALLY ACCESS THE SERVES AND AGAIN THE GENEROSITY OF MANY OF THE JUSTICE SETTINGS WERE SUCH THAT, YOU KNOW THEY TAPPED INTO THEIR OWN RESOURCES TO BE ABLE TO PROVIDE THE CLIENTS WITH THESE--WITH THE TECHNOLOGY BUT THEY ALSO, YOU KNOW DEVOTED TIME TO HELPING PEOPLE UNDERSTAND HOW BEST TO USE THAT TECHNOLOGY. SO WE'VE SEEN A NUMBER OF ADAPTATIONS EVEN TO THE DEGREE OF MANY--A COUPLE OF OUR STUDY SITES THEY HAD WHAT THEY CONSIDERED JOHN SNYDER FROM THE UNIVERSITY OF CHICAGO CALLS IT THE ZOOM ROOMS WHERE IN THEIR CLINICS THEY SET UP A ROOM WHERE PATIENTS CAN GO AND THEN NEXT TO THEM, IN A DIFFERENT ROOM IS A RESEARCH ASSISTANT OR A CLINICIAN TO BE ABLE TO PROVIDE SERVICES. AND YOU KNOW THAT SHOWS ADAPTATIONS THAT PEOPLE HAVE BEEN ABLE TO DO AND THINK ABOUT, WE'VE HAD OTHERS THAT HAVE SET UP TENTS IN PARKING LOTS AS PLACES THAT PEOPLE CAN ACTUALLY GET ACCESS TO SERVICES AND OF COURSE, YOU KNOW, WE'VE SEEN ED NUNES TALKED ABOUT, WE'VE SEEN HOME DELIVERIES OF EDUCATIONS, AND SOME OF OUR PROBLEM SOLVING. >> I THINK LONG-TERM IMPLICATIONS ON IMPROVING ACCESS AND. >> INTERESTING. LIZ HAD HER HAND UP AND SHE HAS INTERESTING THINGS TO SAY, GIVEN THE ADAPTATIONS. >> AND I THINK 1 OF THE THINGS WE HAVE FOUND IS DAN AND I IS THAT IT'S INCREASED OUR ABILITY TO REACH VULNERABLE POPULATIONS, DAN'S BEEN DOING THIS WORK FOR OVER 2 DECADES AND I'VE BEEN WORKING WITH HIM FOR ABOUT A DECADE AND FOR URBAN NATIVE AMERICANS THEY'RE SPREAD OUT AND SO USUALLY WAWE DO IS GO FROM CITY TO CITY AND WORK WITH DIFFERENT ORGANIZATIONS NIEGZATIONS AND WHATIA BEEN GREAT IS BEING ABLE TO USE SOCIAL MEDIA TO CONNECT PEOPLE ACROSS THE UNITED STATES IN THESE WORKSHOPS AND I TALKED ABOUT NETWORKS BUT HAVING THE POSITIVE HEALTHY CONNECTIONS AND HAVING IT BE SPREAD SO MUCH LIGHTER. --SO IT'S BEEN AN INTERESTING JOURNEY AND YOU KNOW I THINK OUR COMMUNITY PARTNERS HAVE ALSO SEEN THAT'S IT'S REALLY A GREAT WAY TO HAVE PEOPLE BE ABLE TO ACCESS RESOURCES THAT MAYBE THEY COULDN'T EASILY GET TO, I MEAN THIS IS HUGE AND FINDING YOUR WAY TO THE RESOURCE IS HARD, IT'S A GREAT WAY TO CONNECT. >> NED, I THOUGHT YOU WERE GOING TO SAY SOMETHING EARLIER SO I WANT TO THROW IT BACK TO YOU. >> NO, I'M--ALTHOUGH I HAD 1 THOUGHT WHICH IS THAT WHAT WE FOUND IN SOME OF OUR RESEARCH IS THAT SETTING A PARTICIPANT UP WITH A CHEAP CELL PHONE OR CHEAP DEVICE CAN BE DONE PRETTY CHEAPLY. PARTICULARLY IF IT'S JUST A DEVICE THAT WILL CONNECT TO THE INTERNET, LET'S SAY AT A LOCAL LIABLEERARY FOR 50 BUCS OR SOMETHING YOU CAN IMIF SOMEBODY A DEVICE THAT'S NOT A FANCY SERVICE IT'S SOMETHING THAT A STUDY OR A CLINICAL PROGRAM CAN EASILY AFFORD. >> I THINK THAT'S A REALLY IMPORTANT POINT BECAUSE I THINK A LOT OF PEOPLE ARE PROBABLY THINKING HOW COST EFFECTIVE ARE THESE, THERE'S A LOT OF TECHNOLOGY HERE, HOW COST EFFECTIVE IS THIS AND I THINK YOU'RE EMPHASIZING THE VALUE OF LOW TECH APPROACHES WHICH I THINK LYNN BROUGHT OUT IN HER TALK, THE WORK BY CANNED WHAT USING IVR APPROACHES WHICH ARE INCREDIBLY INEXPECTATIONS PENSIVE AND ANYBODY THAT'S EVER USED A PHONE HAS USED IT. LET ME TAKE THIS IN A SLIGHTLY DIFFERENT DIRECTION, IF WE TALK PRECOVID, IF YOU TALK TO CLINICIANS AND I THINK FOR SURE INSURANCE CUTCHES, THEY REALLY THINK OF TELEHEALTH OR REMOTE ISHT VENTIONS AS A SECOND CLASS WAY OF TREATING PEOPLE AND YOU KNOW SOMEHOW IT'S OFFERING LESS THAN WHAT CAN BE OFFERED IN PERSON. AND WHAT I WOULD LIKE YOU EACH TO TALK ABOUT IS ARE THERE WAYS THAT TELEHEALTH REMOTE INTERVENTIONS AND THEY CREATE OPPORTUNITIES TO PROVIDE MORE THAN WHAT CAN BE PROVIDED IN PERSON. SO I AM GOING TO THROW IT INENTIALLY TO LIZ BECAUSE I THINK YOU HAVE SOME OF THE MOST CREATIVE WAYS OF GETTING A LITTLE BIT MORE AND THEN I WOULD LIKE LENOIR TO RESPOND NEXT BASED ON SOME OF HER--SO LIZ COULD YOU ADDRESS THIS? CAN WE DO MORE WITH THIS REMOTE APPROACH THAN WE CAN IN PERSON? >> I THINK THERE'S 2 SIDES TO EVERYTHING, AS I SAID, WE HAVE BEEN REALLY PLEASANTLY SURPRISED WITH HOW ENGAGED PEOPLE HAVE BEEN. I THINK FOR A LOT OF PEOPLE, YOU KNOW IT'S EXCITING TO RECEIVE THIS PACKAGE IN THE MAIL FILLED WITH INGREDIENTS FOR THEIR COOKING WORKSHOP, THEIR SAGE THAT'S PICKED BY OUR COMMUNITY PARTNER AND I THINK, YOU KNOW COOKING TOGETHER EVEN THOUGH IT'S A VIRTUALLY AND BEING ABLE TO TALK IS--PEOPLE HAVE BEEN ABLE TO CONNECT. I THINK WHAT OTHER PEOPLE MENTIONED THOUGH ABOUT JUST BEING IN PERSON AND BEING ABLE TO LIKE TOUCH AND BE AROUND PEOPLE AND ALSO IMPORTANT AND SINCE WE HAVE THIS SOCIAL NETWORK PIECE, WE THEN HAD TO THINK REALLY HARD OF HOW WE CAN CONNECT PEOPLE WITH THEIR SOCIAL NETWORKS VIRTUALLY BECAUSE IN PERSON IT MIGHT BE EASIER SO WE HAD TO THINK CREATIVELY ABOUT HOW TO GET PEOPLE TO CONNECT SOCIALLY IN THIS VIRTUAL WORLD. AND MAYBE, YOU KNOW CREATE THESE POSITIVE NETWORKS GIVEN--YOU KNOW WE'VE DONE 45 WORKSHOPS AND I HAVE BEEN REALLY IMPRESSED. WE ALSO HAVE WELLNESS GATHERING THAT WE DO ONCE A MONTH WHERE SOMEONE COMES FROM THE COMMUNITY AND THEY DO SINGING OR DANCING OR TALK ABOUT HEALTH AND IN A COUPLE OF MONTHS WE WILL HAVE THE GREAT GRANDSON OF SITTING BULL DO 1 OF OUR WELLNESS GATHERING SO IT'S A REAL WAY FOR THE COMMUNITY TO COME TOGETHER AND TALK ABOUT YOU KNOW HOW TO HAVE HEGHT AND WELLNESS AND IT'S BEEN VERY SUCCESSFUL. -- >> EMERGING EFDEPT THAT I WOULD LIKE TO BE MADE AWARE OF THAT SOME OF THE CONNECTIONS THAT PEOPLE EXPERIENCE WHEN THEY CONNECT REMOTELY ARE NOT THERAPEUTIC ALLIANCE IS NOT QUITE AS STRONG AND SO ON AND CERTAINLY WITH SOME OF THE TECHNOLOGIES, WE'RE RAISING A QUESTION, MAYBE IT WAS, BUT I'M WONDERING IN YOUR EXPERIENCE, WHAT DO YOU SEE? IS IT MORE THAN OR LESS THAN OR THE SAME DOING IT REMOTELY VERSUS IN PERSON? >> YEAH. IT'S SUCH A GOOD QUESTION THAT BOB RAISED. AND I THINK IT CAN BE BOTH, RIGHT? SO 1 OF THE THINGS I HIGHLIGHTED IN MY TALK WAS ALL THE WAYS YOU CAN PARTICULARLY WITH BEHAVIOR CHANGE, SKILLS TRAINING KINDS OF INTERVENTIONS REALLY CUSTOMIZE AND TAYLOR AND PERSONALIZE AND YOU CAN SEE PEOPLE'S HOUSE, CAN YOU FIGURE OUT WHAT KIND OF ADAPTATIONS ARE NEEDED SOPHISTICATED FRANK, THE WORK YOU'VE DONE WITH VIRTUAL REALITY KINDS OF VERY CHEAP SET UPS THAT WORK WITH IPHONES THAT ALLOW YOU TO DO THAT SO IT CAN FEEL VERY, VERY PERSONAL. ON THE OTHER HAND, YOU KNOW SOMETIMES PEOPLE DON'T WANT THAT, YOU KNOW THEY'RE NOT LIVING IN PLACES WHERE IT FEELS LIKE THEY CAN HAVE A PRIVATE CONVERSATION. THEY MAY REFER THE LOW TECHNESS OF PHONE TO ACTUAL--THE VIDEO FEED AND MAYBE THERE ARE WAYS THAT WE CAN--RATHER THAN IT BEING EITHER OR WE CAN DO BOTH AND. CAN WE FACILITATE SOME IN-PERSON CONTACT AND THEN USE THESE TECHNOLOGIES TO REALLY AUGMENT IT OR, YOU KNOW I THINK AS I DO MORE COLLABORATIVE CARE, I BECOME AWARE THAT IT REALLY IS THIS NETWORK OF SERVICES, RIGHT? AND SO YOU'RE CONNECTING PEOPLE TO PEER SUPPORT THAT'S VERY LOCAL AND YOU'RE WORKING WITH THEM AS A THERAPIST REMOTELY. ONE OF THE--1 OF THE INTERVENTIONS THAT WE HAVE, THAT WE'RE TESTING RIGHT NOW AND FRAIRCHG'S WORKING WITH US ON IS LOOKING AT PAIN TRAINER WHICH IS WONDERFUL ONLINE PLATFORM WHERE WE HAVE SOME SUPPORT, PEOPLE ARE HAVING TECHNICAL PROBLEMS OR SEEMING TO DROP OFF WITH THE VIRTUAL COACH AND SO, FOR WHAT KINDS OF PEOPLE AND WHAT CIRCUMSTANCES DO YOU NEED A LITTLE BIT MORE OF THAT LIVE PERSON FOR? SO THERE ARE A NUMBER OF REALLY RICH WAYS TO JUST EXPLORE THESE THINGS, SO THANKS. >> COOL. I WOULD LIKE TO TEE UP A QUESTION FOR KEVIN HERE AND 1 THING THAT STRUCK ME IS JUST THE NAME OF THE PROJECT THAT HE'S INVOLVED IN AND PART OF THE REASON IT STRUCK ME AS I LISTEN TO THE PRESENTATION, THE PLENARIES AND THE PANELISTS THERE IS A KIND OF THEME ABOUT BEING MORE POSITIVE, ABOUT WHAT WE DO AND BUILDING STRENGTH AND RESILIENCE AND THIS IS REALLY COUNT TORE OFTEN WHAT GOES ON IN WORKING WITH THESE POPULATIONS WHERE IT'S LIKE, LET'S FIND OUT THE PROBLEMS, REDUCE THE PROBLEMS, DIMINISH THE PROBLEMS, MORE OF A PROBLEM FOCUS THAN RESILIENCE FOCUSED AND KEVIN, I WONDER IF YOU COULD TALK SOME ABOUT THAT, START US OFF ON THAT AND THEN I MAY ASK OTHERS TO RAISE THEIR HAND AND CHIME IN AS TO WHY IS THAT IMPORTANT. >> SURE. THANKS, FRANK FOR THAT QUESTION. PART OF THE BASIS OF THE TREATMENT APPROACH WE'RE USING IS TO HELP PEOPLE WITH PERSISTENT PAIN THAT IS NEVER GOING AWAY, REALLY, BUILD LIVES THAT ARE FILLED WITH MEANING AND EFFICACY AND VITALITY AND VALUES. AND WHAT WE FOUND OVER THE YEARS IS THAT THAT APPROACH SEEMS TO REASONABLY WELL, EVEN WITH PEOPLE WHO WILL HAVE PAIN FOR THE FORESEEABLE FUTURE AND THAT HAS BEEN AN EMPHASIS OF PSYCHOLOGICAL OR BEHAVIORIAL INTERVENTIONS ALL ALONG AND I THINK IT'S BECOMING AN INCREASE BIT OF EVIDENCE BUT AN OPINION BASED 1 THAT SEEMS PARTICULARLY RELEVANT WHEN WE ARE TALKING ABOUT INDIVIDUALS WITH OPIOID USE DISORDER OR OPIOID USE A POPULATION THAT HAS INCREASED BEEN MARGINALIZED BECAUSE OF ALL KINDS OF THINGS GOING ON, OFTEN LIVING IN IMPOVERISHED CIRCUMSTANCES, WE HAVE DATA IN NORTHERN IRELAND WHERE THEY COME FROM THE MOST DEPRAVED SOCIOECONOMIC CIRCUMSTANCES, SIGNIFICANT RISK FACTOR AND I- THINK THE PANELISTS ON HERE AND THE ATTENDEES OF THIS MEETING, THAT WILL RING TRUE FOR EVERYONE. --DEPRIVED, I DON'T KNOW WHAT I SAID BUT THANK YOU VERY MUCH, FRANK, FROM DIFFICULT CIRCUMSTANCES, WHY DON'T I JUDGE UTV SAY THAT. >> YEAH. >> AND THE PILOT WORK WE'VE DONE AS WELL AS OTHER STUDIES THAT ARE OUT THERE INDICATE THAT INDIVIDUALS WITH THE SIGNIFICANT CO-MORBIDITIES RESPOND REASONABLY WELL TO TREATMENT IN OVERALL QUALITY OF LIFE IMPROVES AND AS QUALITY OF LIFE IMPROVES, HAZARDOUS UNHEALTHY BEHAVIORS TEND TO DECREASE. THE OTHER THING I WOULD JUST LIKE TO ADD BRIEFLY IN RELATION TO THE FIRST QUESTION ABOUT INCREASING CAPACITY IS WHAT I HAVE SEEN AS A RESULT OF THESE COVID INDUCED CHANGES IN PRACTICE IS THAT THERE'S MUCH MORE APPETITE FROM FUNDERS AND HEALTHCARE SYSTEMS TO PROVIDE TELEHEALTH INTERVENTION ASKS THAT IS SOMETHING WE SHOULD ALL SEEK TO CAPITALIZE ON BECAUSE IT JUST ENHANCES REACH AND OF COURSE THERE'S OTHER QUESTIONS AND THERE'S OTHER PROBLEMS BUT IF YOU'VE EVER DONE RESEARCH IN A VA, IT'S REALLY HARD TO GET THINGS THROUGH IRB AND WE WERE ABLE TO GET THEM TO APPROVE A TELEHEALTH STUDY IN RECORD TIME IN PART BECAUSE OF COVID RELATED PRESSURES. THE NATIONAL HEALTH SERVICE IN THE UK WHICH HAS BEEN HOSTILE TO TELEHEALTH DISTANCED INTERVENTIONS HAS HOW EMBRACED IN TECHNOLOGY SO THERE IS ONLY--THERE ARE A NUMBER OF UNANSWERED QUESTIONS, BUT 1 OF THE THINGS WE NEED TO CAPITALIZE ON HERE IS THE INCREASED REACH AND PENETRATION TO THE RURAL AND IMPOVERISHED AREAS. >> I THOUGHT NED DID SUCH A GOOD JOB OF EMPHASIZING, IT'S ALMOST HEAD SWIMMING HOW QUICKLY THINGS CHANGED AND PEOPLE OPENED UP TO THESE APPROACHES AND IT'S JUST REMARKABLE. SO, JUST, YOU KNOW IT'S REALLY QUITE STRIKING AND YOU DO WONDER ARE WE GOING TO SEE IT MOVING BACK OR ONCE YOU OPEN THE DOOR AND WONDER WHAT YOU ARE THINKING ABOUT THAT, NED? >> I HOPE WE DON'T MOVE BACK BUT I EMPHASIZED THAT WE NEED EVIDENT AND THERE ARE A NUMBER OF STUDIES THAT WILL GENERATE EVIDENCE ON YOU KNOW THE COMPARATIVE EFFECTIVENESS OF IN PERSON VERSUS REMOTE, YOU KNOW THE NEW WAYS OF DOING THINGS WITH TECHNOLOGY AND VIRTUAL CONTACT AS OPPOSE TO IN-PERSON BUT I THINK TAKING ADVANTAGE OF THE REMOTE TECHNOLOGY AND THE DIGITAL INTERVENTIONS, IT JUST MAKES SO MUCH SENSE AND RIGHT NOW, YOU KNOW MOSTLY WE HAVE ANECDOTES BUT I WAS ON THE PHONE A COUPLE DAYS AGO WITH A COLLEAGUE I TALK WITH OCCASIONALLY WHO RUNS A NOT FOR PROFIT ADDICTION TREATMENT PROGRAM IN THE NEW YORK AREA AS THE ADMINISTRATOR AND HAS DONE SO FOR 30 YEARS AND SHE SAID, OH, WE'RE TWICE THE TWICE THAT WE WERE BEFORE COVID STARTED. WE'VE DOUBLED OUR VOLUME. WE CAN'T HIRE ENOUGH THERAPISTS, THEY'RE GOING GANG BUSTERS AND THEY'RE JUST DOING THERAPY OVER ZOOM. SO I THINK THE CAT'S OUT OF THE BAG, THIS STUFF IS WELL ACCEPTED AND WE JUST NEED MORE RESEARCH ON HOW WELL IT WORKS AND HOW TO REALLY OPTIMIZE HOW WELL IT WORKS. ONE OF MY WORRIES ABOUT SOME OF THE DIGITAL INTERVENTIONS THAT IS THAT YOU KNOW AN APP OR SOMETHING LIKE THIS BY ITSELF, THERE'S IN NOTION IN THE FIELD OF APPS, THAT THE LAW OF ATTRITION WHICH IS THAT THE PEOPLE SIGN UP FOR AN APP AND THEN THEY YOU KNOW OFTEN ABANDON IT FAIRLY QUICKLY AND MY HYPOTHESIS IS THAT FOR A LOT OF THESE KINDS OF HEALTH APPS, YOU WILL NEED THE HUMAN TOUCH. YOU WILL NEED A HUMAN THERAPIST, IT WILL WORK BETTER AS THE CLINICIAN EXTENDER MODEL RATHER THAN AS A STAND ALONE. BECAUSE YOU STILL NEED THE HUMAN TOUCH THERE, BUT I--I THINK--I HOPE WE CAN LEARN HOW TO GET PAST SOME OF THOSE OLD BARRIERS IN TERMS OF RESEARCH PRACTICE. >> YEAH, WELL, LET ME ASK FAYE AND LYNN TO CHIME IN ON THIS PARTICULAR ISSUE, IT'S MORE OF THE RESEARCH, BUT EACH OF YOU BECAUSE OF THE WORK THAT YOU'VE DONE, YOU'VE REALLY BEEN DOING THIS FOR A WHEEL OR DOING IT ACROSS MULTIPLE PROJECTS AND I THINK FUNDERS ARE ALWAYS INTERESTED, YOU KNOW CAN YOU RECRUIT, CAN YOU SCREEN, CAN YOU ENROLL, CAN YOU DATA COLLECT REMOTELY AND I'M SURE THAT YOU BOTH HAVE LEARNED LESSONS AS TO WHAT THE ADVANTAGES AND DOWN SIDES OF THIS REMOTE APPROACH TO THESE RESEARCH IMPORTANT ACTIVITIES AND PAIB WE COULD START OFF WITH FAYE? WHAT'S THE EXPERIENCE IN YOUR NETWORK WITH HOW IT'S GOING? WHAT ARE THE PROS AND CONS OF DOING THIS THING REMOTELY? >> WELL, BEFORE WE MOVE ON TO THAT, I JUST WANT TO FOLLOW UP ON WHAT NED WAS TALKING ABOUT IN TERMS OF SOME OF THE DIGITAL. SO, YOU KNOW IN 1 OF THE STUDIES THAT WE HAVE WHERE WE'RE TESTING OUT A TELEHEALTH ZOOM THERAPY WE ACTUALLY HAVE ASSIGNED SOCIAL WORKERS TO BE PEER NAVIGATORS TO WORK WITH CLIENTS BECAUSE, YOU KNOW WE FIND THAT THOSE WHO ARE READY TO ENGAGE IN THERE SEEM TO DO BETTER WITH THE TECHNOLOGY BUT THOSE WHO ARE HAVING DIFFICULTIES, IN THEIR LIVES OR NEED SOME ADDITIONAL, YOU KNOW SUPPORT, NEED ACTUALLY SOME OF THE PEER NAVIGATORS OR SOME SORT OF, YOU KNOW CLINICAL ASSISTANCE. SO I REALLY THINK WE'RE ON THE VERGE OF RETHINKING HOW WE DELIVER SERVICES TO THESE INDIVIDUALS WITH VARIOUS NEEDS, AND USING KIND OF THE VARIETY OF TOOL KITS TO REALLY DEAL WITH THAT. SO I JUST--I WANTED TO DO THAT AND SAY THAT. NOW TO GET TO YOUR QUESTION ABOUT ENGAGING, SO, YOU KNOW I THINK THAT WE'VE HAD--SOME OF THE STUDIES HAVE DONE REALLY WELL WHEN PEOPLE ARE INCARCERATED AND THEY'VE BEEN ABLE TO ACTUALLY, YOU KNOW PEOPLE ARE ABLE TO, YOU KNOW CONSENT TO CARE AND PEOPLE HAVE USED VARIOUS ALTERNATIVE SIGNATURE FORMS FOR CONSENTS BUT WE'VE ALSO SEEN SOME DIFFICULTIES IN COMMUNITIES BECAUSE OF TRYING TO FIND WAYS IN WHICH WE COULD FIND PEOPLE TO ACTUALLY TRY AND RECRUIT IN SOME OF THE MORE DIFFICULT COMMUNITIES BUT YET THE RESEARCHERS, YOU KNOW HAVE DONE SOME VERY CREATIVE, I THINK THEY'RE VERY SIMILAR TO WHAT LIZ HAS TALKED ABOUT HERE, WAYS OF TRYING TO ENGAGE PATIENTS BY SENDING DIFFERENT YOU KNOW THINGS TO THEIR HOUSE OR ELECTRONICALLY BY REALLY TRYING TO USE AS I SAID SOMEONE--1 OF OUR SITES, THE CHEST NUT SITE IN CHICAGO SET UP A CENTER IN A GARAGE AND HAD A VERY ELABORATE SORT OF LIGHTS AND, YOU KNOW SOMETHING VERY APPEALING THAT WOULD REALLY MAKE PEOPLE FEEL COMFORTABLE TO COME THERE. SO, YOU KNOW IT'S BEEN MIXED BUT MORE ON THE POSITIVE SIDE AND THE SENSE THAT IT'S GIVEN ALL OF US, I THINK AS RESEARCHERS, OPPORTUNITIES TO BE CREATIVE. THE OTHER THING I WANTED TO NOTE IS 1 OF THE THINGS THAT WE HAVE FOUND, A LOT OF OUR STUDIES ARE ORGANIZATIONAL CHANGE, IMPLEMENTATION SCIENCE STUDIES AND THE PLATFORMS HAVE ACTUALLY MADE IT A LITTLE BIT EASIER TO OBSERVE TEAM PROCESSES AND EVEN TO COLLECT QUALITATIVE DATA ON WHAT'S GOING ON IN THE TEAM PROCESSES. OUR UNIVERSITY INDIANA TEAM BASICALLY HAS INDICATE THAD YOU KNOW THEY'RE ABLE TO REALLY REVIEW LOCAL PLAYERS AND HOW THEY DO, YOU KNOW TEAM WORK THAT HAS REALLY ACCELERATED SOME OF THEIR OWN RESEARCH IN TERMS OF UNDERSTANDING TEAM PROCESSES. SO THERE ARE SOME REAL UPSIDES BUT, YOU KNOW THE ISSUES ABOUT HOW TO RECRUIT AND KEEP PEOPLE RETAINED AND STUDIES ARE CHALLENGES, I THINK PEOPLE ARE WORKING THROUGH. >> YEAH, I'M SORRY BUT WE DO NEED TO TRANSITION, SO LYNN I WILL NOT BE ABLE TO GIVE YOU A CHANCE TO RESPOND. WE NEED TO TRANSJUST A BIT EARLY. I WANT TO THANK THE PRESENTERS AND THE PANELISTS. THIS HAS BEEN A TERRIFIC DISCUSSION AND I HOPE THAT EACH OF YOU WILL BE WILLING TO ENTERTAIN FOLLOW UP QUESTIONS. FASCINATING. THANK YOU SO MUCH FOR THIS. >> THANK YOU. >> AND FOR THE OPPORTUNITY TO GET US ALL TOGETHER. >> THANK YOU. >> THANK YOU. >> THANK YOU. >> THANKS TO ALL OF THE PANELISTS. THAT BRINGS THIS SESSION TO AN END. WHAT AN EXCITING LOOK AT EFFORTS TO ADAPT HEAL RESEARCH, TO DEAL WITH THE REALITIES OF COVID-19 AND ITS IMPACTS ON PAIN OVERDOSE AND THE ADDICTION CRISIS. I WOULD NOW LIKE TO GET STARTED WITH OUR NEXT SESSION AND INVITE DR. LARRY TABAK TO JOIN US, ARE YOU ON? >> YES I AM REBECCA. >> OKAY, THANK YOU. >> CAN YOU HEAR ME? >> YES, I CAN. I WANTED TO MAKE SURE WE HAVE OUR PANELISTS INERED ONER FOR THIS NEXT SESSION. AND I THINK I SEE EVERYONE ON. IF YOU ARE PANELISTS FOR THIS NEXT SESSION, COULD YOU PLEASE TURN YOUR VIDEO ON. >> OKAY, THANK YOU. SO IT'S NOW PLIE PLEASURE TO INTRODUCE DR. LARRY TABAK, PRINCIPLE DIRECTOR OF THE NIH, HE SERVED AS THE DIRECTOR OF THE NATIONAL INTUITY OF DENTAL AND CRANEIO FACIAL RESEARCH FROM 2000 TO 2010 EMPLOY HE HAS PROVIDED LEADERSHIP FOR NUMEROUS TRANSNIH ACTIVITIES SUCH AS NIH ROADMAP EFFORT ON TEAM SCIENCE, AND NIH EFFORT TO ENHANCE RIGOR AND PREPRODUCE ABILITY AND RESEARCH AND LEAD NIH EFFORTS IN NEXT GENERATION RESEARCHERS AND REWARD RESEARCH, ARTIFICIAL INTELLIGENCE AND DATA SCIENCE PLANNING EXPOSURE TO RADIATIONS. HE HAS OVERSEEN THE EVOLUTION OF PAIN RESEARCH AND NIH OVER THE PAST SEVERAL DECADES AND HE--WE ARE SO GRATEFUL TO HAVE HIM AS A LEADER IN THE NIH HEAL INITIATIVE. DR. TABAK WILL NOW FACILITATE THIS PANEL OF LEADERS WITHIN THE U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES WHO WILL SHARE THEIR RESPECTIVE AGENCIES ARE EVOLVING TO ADDRESS THE DUAL PAIN AND OPIOID CRISIS IN THE WAKE OF COVID-19 COLLABORATING WITH PARTNERS, AND OTHER FEDERAL AGENCIES TO ADDRESS THESE CRISIS. AND THEY WILL ALSO SHARE THEIR PERSPECTIVES ON HOW NIH AND NIH HEAL INITIATIVE RESEARCH COMMUNITY CAN FRAME RESEARCH RESULTS IN A WAY THAT'S MEANINGFUL AND DIVERSE STAKEHOLDERS AND INFORM THEM TO USE DIVERSE POLICY AND PRACTICE. WELCOME DR. TABASH --TABAK. >> THANK YOU VERY MUCH FOR THE INTRODUCTION AND THE INTRODUCTION TO THE SESSION AND GOOD MORNING EVERYBODY. IT'S A GREAT PLEASURE TO BE HERE WITH YOU LET ME BRIEFLY INTRODUCE MY COLLEAGUES FROM ACROSS GOVERNMENT WHO WILL BE THE PANELISTS TODAY AND THEN WE WILL INVITE EACH OF THEM TO PROVIDE THEIR PERSPECTIVE AND SO TO BEGENERATED THE FIRST PANELIST IS MR. TOM CODERRE, WHO IS THE ACTING ASSISTANT SECRETARY FOR THE SUBSTANCE ABUSE AND MENTAL HEALTH SERVICES ADMINISTRATION. MR. CODERRE HAS DECADES IN PRIVATE AND NONPROFIT SERVICE AND HE IS THE FIRST PERSON IN RECOVERY TO LEAD SAMHSA. HIS CAREER HAS BEEN INFLUENCED BY HIS PERSONAL JOURNEY AND PHILOSOPHY THAT ACKNOWLEDGES THE ESSENTIAL ROLE THAT PEER RECOVERY SUPPORT SERVICES PLAY THIS HELPING PEOPLE WITH MENTAL AND SUBSTANCE USE DISORDERS REBUILD THEIR LIVES. WELCOME MR. CODERRE. WE ALSO HAVE WITH US DR. DEBORAH HOURY, WHO JOINED THE CENTERS FOR DISEASE CONTROL AND PREVENTION IN OCTOBER OF 2014 AS THE DIRECTOR FOR THE CENTER FOR INJURY PREVENTION AND CONTROL AND IN THIS ROLE, SHE LEADS INNOVATIVE RESEARCH AND SCIENCE BASED PROGRAMS TO PREVENT INJURIES IN VIOLENCE AND TO REDUCE THEIR CONSEQUENCES. AND THEN OUR THIRD PANELIST DR. JANET WOODCOCK WHO WAS NAMED ACTING COMMISSIONER, FDA, DR. WOODCOCK OVERSEES THE FULL BREDTH OF THE FDA PORTFOLIO AND EXECUTION OF THE FEDERAL FOOD, DRUG AND COSMETIC ACT AS WELL AS OTHER APPLICABLE LAWS. A PERSONAL NOTE. I WANT TO JUST LET EVERYBODY KNOW HOW MUCH I VALUE DR. WOODCOCK'S EXTRAORDINARY LEADERSHIP OF OUR NATION'S RESPONSE TO THE COVID-19 PANDEMIC AND OF COURSE THE MANY OTHER THINGS I'VE HAD THE PRIVILEGE TO INTERACT WITH HER OVER THE YEARS. SO WITH THOSE INTRODUCTIONS WHAT I WOULD LIKE TO DO NOW IS TO INVITE EACH PANELIST TO MAKE SOME INTRODUCTORY COMMENTS IF WE COULD LIMIT THOSE TO ABOUT 10 MINUTES EACH IN TWHA INTRODUCTORY SET OF COMMENTS IF YOU COULD SORT OF SKETCH YOUR AGENCY'S EFFORTS TO RESPOND TO THE OPIOID CRISIS I'M SURE OUR PARTICIPANTS WOULD INCREASE IN BODY QUITE INTERESTING AND SO, WHY DON'T WE JUST GO IN ALPHABETICAL ORDER AND WE WILL BE BEGIN WITH MR. CODERRE. >> THANK YOU SO MUCH DR. TABAK AND GOOD AFTERNOON TO EVERYONE. IT'S GREAT TO JOIN MY COLLEAGUES DR. WOODCOCK AND DR. HOURY ON THIS PANEL THIS MORNING, LEADING INTO THIS AFTERNOON. I WANT TO THANK DR. COLLINS ALSO AND NIH FOR SAMHSA'S INVITATION TO SPEAK AT TODAY'S PANEL AT THE SECOND ANNUAL NIH HEAL INVESTIGATOR MEETING. AT SAMHSA, WE WORK TO HELP ALL AMERICANS UNDERSTAND THAT THEIR BEHAVIORIAL HEALTH IS ESSENTIAL TO OVERALL HEALTH, PREVENTION WORKS, INTERVENTION IS CRITICAL, TREATMENT IS EFFECTIVE AND THAT PEOPLE RECOVER. PEOPLE JUST LIKE ME AND PERHAPS JUST LIKE SOME OF YOU. YOU SEE I JOINED TODAY AS DR. TABAK NOT ONLY AS ACTING ASSISTANT SECRETARY FOR MENTAL HEALTH AND FOR ME, THEY HAVEN'T USED DRUGS SINCE MAY OF 2003 SO I CELEBRATED 18 YEARS ON THIS JOURNEY THIS PAST WEEKEND, SO I'M HONORED TO BE ABLE TO BRING MY EXPERIENCE TO LEAD ING THIS IMPORTANT AGENCY. MY STORY AS YOU HEARD, I LOST MY JOB AS A STATE SENATOR IN RHODEI LAND, LOST RELATIONSHIPS WITH THOSE I LOVED AND SOCIAL OUTGOING, ENGAGING SOUTH TO SOME YOUNG MAN WHO RESEMBLED ME BUT WHO HAD BECOME ALONE AND SICK, A GUY WHO HAD LOST ALL HOPE. I FOUND HOPE AGAIN THROUGH TREATMENT AND RECOVERY SUPPORTS THAT ABSOLUTELY UNEQUIVOCALLY SAVED MY LIFE. HOPE ISN'T SOMETHING WE CAN GET BY WITHOUT BAUDS WE'RE ALL LEARNING DURING THIS PANDEMIC. ALTHOUGH I DIDN'T KNOW IT AT THE TIME, SAMHSA WAS HARD AT WORK AT HELPING ME GET MY HEALTH BACK, THE TREATMENT I RECEIVED WAS FUNDED BY SAMHSA DOLLARS, AND RECOVERY I RECEIVED POST TREATMENT WAS FUNDED BY A DISCRETIONARY GRANT KNOWN AS THE RECOVERY COMMUNITY SERVICES PROGRAM. THE BOTTOM LINE IS I WAS ABLE TO GET THE HELP I NEED. IN MY LIFE, IT'S GOTTEN A WHOLE LOT BETTER AND IN FACT, BEING IN RECOVERY HAS NOT ONLY ENABLED ME TO CREATE A BETTER LIFE FOR MYSELF, BUT IT'S ENABLED ME TO CREATE A BETTER LIFE FOR ME AND MY FAMILY AND ULTIMATELY FOR MY ENTIRE COMMUNITY BECAUSE RECOVERY IS SO MUCH MORE THAN JUST NOT USING ALCOHOL AND DRUGS, IT'S CREATING A BETTER LIFE, IT'S CHANGING EVERYTHING AROUND YOU, IT'S A PROCESS, A PROCESS OF REGAINING, RECLAIMING AND REIMAGINING 1'S LIFE. IT'S NOT LOST ON ME THAT I WAS 1 OF THE PRIVILEGED 1S, 1 OF THE ROUGHLY 10% OF AMERICANS WITH A SUBSTANCE USE DISORDER WHO RECEIVED TREATMENT. WHILE THE NUMBER WHO RECEIVED TREATMENT FOR O. U. D. IS CLOSER TO 30% IT'S STILL AN UPACCEPTABLE GAP AND WE MUST DO BETTER AND THAT'S WHAT EXCITES ME MOST ABOUT HEAL AND AS PART OF THE NIH HEAL INITIATIVE, SAMHSA HAS BEEN ENGAGED ALSO KNOWN AS HCS FOR THE LAST 2 YEARS HAS BEEN A PLEASURE FOR SAMHSA TO HAVE THIS COLLABORATION WITH NIDA AND THE FULL CONSORTIUM OF GRANTEES IN KENTUCKY, OHIO, NEW YORK, MASSACHUSETTS, AND THE DATA COORDINATION CENTER AT RTA INTERNATIONAL WHO HAVE WORKED ON THIS STUDY. THE HCS STUDY'S GOAL IS TO REDUCE OPIOID FATALITIES BY 40% OVER A 3 YEAR PERIOD. AND IT'S AMBITIOUS TO SAY THE LEAST. I KNOW INDIVIDUALS ACROSS THE HCS CONSORTIUM HAVE WORKED CREAMILY HARD TO LAWRCH THIS PROJECT AT THIS MEETING. THE WORK YOU ARE DOING IS VITALLY IMPORTANT TO PEOPLE STRUGGLING WITH OPIOID DISORDER, AND HCS WILL HELP TO INFORM THE INTERVENTIONS AND EVIDENCE-BASED PRACTICES THAT SAMHSA SUPPORTS AND HIGHLIGHTS THROUGH OUR GRANT PROGRAMS AND THROUGH OUR TECHNICAL ASSISTANCE SERVICES. AS A SERVICE DELIVERY AGENCY, SAMHSA UTILIZES RESEARCH FROM NIH TO IMFORMAUR SERVICE MODELS, SAMHSA LOOKS FOR TO USING THESE THAT INTERVENTION RATHER BEING TESTED IN HCS WILL INFORMURE GRANT PROGRAMS, I ALSO WANT TO ACKNOWLEDGE THE IMPORTANCE OF THE HCS WORK AND ALL OF THE HEAL INITIATIVE WORK THAT NIH SUPPORTS HAS BEEN SUPPORTING DURING THE PANDEMIC AS WE HAVE SEEN BY RECENT DATA, COVID-19 HAS EXACERBATED THE HEALTH MEANS TO WHO WE SERVE IN AMERICA. I WANT TO HIGHLIGHT SOME OF SAMHSA PRIORITIES AND INITTIAIVE ITS TO ADDRESSING THE OPIOID CRISIS THAT MAY BE HELPFUL FOR YOU TO KNOW ABOUT. IF YOU DO NOT ALREADY, WHICH I'M SURE MANY OF YOU DO BECAUSE YOU WORK SO CLOSELY WITH US ON THESE. THE FIRST IS OUR STATE OPIOID RESPONSE GRANTS. SHAM CONTINUES TO FUND THE STATE OPIOID ABUSE PROGRAM ALSO KNOWN AS SOAR BUILDING ON THE CARE ACT AUTHORIZED STATE TARGETED RESPONSE PROGRAM, STR BACK IN 2017. THE SOAR INITIATIVE PROVIDED 1.5 BILLION DOLLARS TOTAL TO STATES TRIBES AND TERRITORIES TO DEVELOP AND IMPLEMENT TO COMBAT THE OPIOID CRISIS IN THEIR JURISDICTIONS, SAMHSA MAKES OPIOID USE DISORDER AVAILABLE TO CLIENTS WITH O. U. D. THEY ALSO PREPORT STRATEGIES TO INSURE THAT THE FULL SPECTRUM OF SERVICES ARE BEING ADDRESSED. IN THE MOST RECENT ITERATION OF SOAR, SAMHSA PROVIDED ADDITION ALEX FROMMIBILITYS FOR USE OF STIMULANT ABUSE, AS YOU KNOW CONGRESS GAVE US THAT EXEMPTION LAST YEAR. AND THIS IS SUPER IMPORTANT OF COURSE BECAUSE WE KNOW POLYDRUG USE HAS BEEN ON THE RISE AND CONTRIBUTING TO OVERDOSE DEATHS IN THE REASON YEARS. THE SECOND POINT I WANT TO MAKE IS AROUND FENTANYL STRIPS. WE WORK CLOSELY WITH COLLEAGUES AT THE CDC AND ANNOUNCE ON APRIL 7th OF THIS YEAR THAT PROGRAM FUNDS FROM BOTH AGENCIES MAY NOW BE USED FOR RAPID TESTING. THIS POLICY CHANGE INTENDS TO HELP CURVE THE DRAMATIC SPIKE IN DRUG OVERDOSE DEATHS LARNLLY DRIVEN BY THE USE OFOIDS INCLUDING FENTANYL THIS POLICY ARRANGES TO BOTH SAMHSA AND CDC AS WELL AS TEST STRIPS IS CONSISTENT WITH THE PURPOSE OF THE PROGRAM AND THEN I WAS PLEASED TO BE ABLE TO DO AN OPED RECENTLY WITH DIRECTOR WOLINSKI AND LABELL AT OMDCP TALKING ABOUT THE IMPORTANCE OF THIS INTERVENTION AND HOW WE CAN USE IT TO CONNECT WITH PEOPLE IN COMMUNITIES AND ENGAGE THEM. I WAS HEARING PREVIOUS PANEL TALK ABOUT ENGAGEMENT STRATEGIES EARLIER AND HOW WE CAN USE THESE IMPORTANT TOOLS FOR ENGAGEMENT OF PEOPLE TO GET THEM THE HELP THAT THEY NEED ULTIMATELY. THE THIRD MING I WANTED TO MENTION TODAY WAS THE [INDISCERNIBLE]. ON APRIL 27th, HHS IN PARTNERSHIP WITH MANY OF OUR AGENCIES ANNOUNCED THAT IT WOULD EXEMPT ELIGIBLE PROVIDERS FROM OBTAINING A WAIVER TO TREAT UP TO 30 PATIENTS WITH BUPRENORPHINE FOR OPIOID USE DISORDER. THIS WAS NOT JUST FOR PHYSICIANS BUT IT WAS ALSO FOR ALL THE GROUPS OF PRESCRIBERS, PHYSICIAN ASSISTANTS, NURSE PRACTICE RESEARCH IGDZERS, CLINICAL NURSE, SPECIALISTS, CERTIFIED NURSE, REGISTERED NURSE, AN ESTIMATE THAD THEY--THIVITIES AND CERTIFIED NURSE, THIS POLICY CHANGE INTENDS TO REDUCE BARRIERS IF ARE PROVIDING BUPRENORPHINE FOR INDIVIDUALS WITH OPIOID USE DISORDER AND THUS INCREASE ACCESS TO TREATMENT FOR THOSE WHO DPEED NEED IT. ESPECIALLY IN RURAL AREAS WHERE TREATMENT IS A LOT MORE SPARSE. FOURTH THING I WANT TO MENTION IS AROUND BLOCK GRANT FUNDING. SINCE DECEMBER SAMHSA HAS AWARDED NEARLY 5.5 BILLION DOLLARS IN FUNDING TO STATES. IN FACT WE,A NOUNSED 3 BILLION--IN SUBSTANCE USE INCLUDING OPIOID, MENTAL ILLNESS, THAT CO OCCURS FREQUENTLY WITH THESE CONDITIONS WHICH HAVE WORSENED SINCE THE COVID PAN DEMI SAMHSA DIRECTED 2.5 FROM THE COVID RELIEF BILL AND 3 MILLION FROM THE RESCUE PLANS TO STATES AND TERRITORIES IN 1 TRIBE AS I MEPGZED, WE PROVIDED GUIDANCE TO THE STATES ABOUT HOW TO USE THESE RESOURCES TO MAKE REAL INVESTMENTS IN THE FULL CONTINUUM OF PREVENTION, INTERVENTION, TREATMENT AND RECOVERY SUPPORT. THE FIFTH THING I WANTED TO MENTION TODAY WAS OTHER DISCRETIONARY PROGRAMS. A FEW ADDITIONAL DISCRETIONARY SAMHSA WHICH ADDRESS OPIOIDS THAT I WANT TO HIGHLIGHT INCLUDE THE NEW EMERGENCY DEPARTMENT ALTERNATIVE TO OPIOID GRANT. THIS PROGRAM INTENDS TO IDENTIFY ALTERNATIVES TOOIDS FOR PAIN MANAGEMENT IN ADDITION SAMHSA COLLABORATIVE TO CDC TO EVALUATE PRESCRIPTION DRUG OVERDOSE GRANT PROGRAM. THE PROGRAM. SINCE 2016. THE PURPOSE OF THIS PROGRAM IS TO REDUCE THE NUMBER OF PRESCRIPTION DRUG AND OPIOID OVERDOSE RELATED DEATHS AND ADVERSE EVENTS IN INDIVIDUALS 18 YEARS OF AGE OR OLDER. THE PROGRAM ALSO INTENDS TO FOCUS ON SECONDARY PREVENTION STRATEGIES INCLUDING THE PURCHASE AND DISTRIBUTION OF NALOXONE TO FIRST RESPONDERS AND THEN THE LAST PROGRAM I WANT TO MENTION WAS AROUND EVIDENCE-BASED PRACTICES. THE 21st CENTURY CURES ACT DIRECTS SAMHSA TO PROMOTE ACSETIONZ TO RELIABLE, AND VALID INFORMATION ON EVIDENT-BASED PROGRAMS AND PRACTICES AND SHARE INFORMATION ON THE STRENGTH OF EVIDENCE ASSOCIATED WITH SUCH PROGRAMS AND PRACTICES RELATED TO MENTAL ILLNESS AND DRUG AND CONTROL ADDICTION. TO FULFILL THIS CHARGE, SAMHSA DEVELOPED EVIDENT BASED PRACTICE RESOURCE CENTER WHICH PROVIDES BEHAVIORIAL HEALTH, INFORMATION ON EVIDENCE-BASED PROGRAMS AND PRACTICES TO STATES, LOCAL COMMUNITIES, NONPROFIT ENTITIES AND OTHER STAKE TOLDERS, PRODUCTS IN THE EVIDENT BASED RESOURCE CENTER THAT ARE RELEVANT TO OUD INCLUDE IMPLEMENTATION OF MEDICATIONS FOR OPIOID USE DISORDER IN EMERGENCY DEPARTMENTS AND AS WELL AS IMPLEMENTATION OF MEDICATIONS FOR MEDICAID USE DISORDER IN CRIMINAL JUSTICE SETTINGS, I WANT TO END BY SAYING SAMHSA LOOKS FORWARD TO CONTINUING WITH NIH NIDA AND HCS AS WELL AS OTHER FEDERAL PARTNERS INCLUDING THE CDC, FDA, SURGEON GENERAL WHO HAVE ALL BEEN SPEAKING TO YOU GUYS THROUGHOUT THIS IMPORTANT CONFERENCE THIS WEEK. WE ARE REALLY LOOKING FORWARD TO WORKING TOGETHER TO END THE OPIOID CRISIS. THANK YOU. >> WELL, THANK YOU SO MUCH MR. CODERRE, THAT GOT US OFF TO A GREAT START. AND NOW, I WOULD LIKE TO TURN TO DR. HOURY FROM THE CDC. >> THANK AND YOU GOOD AFTERNOON ALL, THANK YOU FOR THE OPPORTUNITY TO SPEAK ABOUT CDC'S EFFORTS TO PREVENT OVERDOSE AND AREAS FOR POTENTIAL COLLABORATION. I'M THRILLED TO JOIN YOU ALL VIRTUALLY TODAY, AND I REMEMBER JOINING YOU IN PERSON 2 YEARS AGO AND HOPEFULLY WE WILL GOET TO THAT SOON, THE HAT I WEAR AND I'M AN EMERGENCY PHYSICIAN AND I WORK IN A CLINIC WITH MEDICATIONS FORROID USE DISORDER SO I THINK THAT'S A NICE SYNERGY FOR THE WORK AT CDC IS TO REALLY HAVE THAT PRACTICE BASED EXPERIENCE AS WELL. SO I LOOK FORWARD TO ENGAGING WITH MY PANELISTS AND ALL OF YOU AFTER THESE PRESENTATIONS IN A ROBUST DISCUSSION, BUT AS WITH MANY OF YOU, OUR FOCUS THIS YEAR AS BEEN ON THE EVOLVING OVERDOSE EPIDEMIC BEING CHALLENGED BY COVID-19 AND THE CHANGE IN DRUG LANDSCAPE. OUR OVERDOSE PREVENTION EFFORTS HAVE BEEN PRIORITIZE INTO 6 AREAS INCLUDING ADVANCING RESEARCH, MONITORING TRENDS ISSUES USING OUR DATA, REALLY BUILDING STATE AND TRIBAL, LOCAL AND TERRITORIAL CAPACITY TO FILL UP EVIDENCE-BASED PREVENTION PROGRAMS, CONTINUING TO SUPPORT HEALTH SYSTEMS PROVIDERS AND PAYORS TO IMPROVE PATIENT SAFETY, AND THEN ENGAGING THE PUBLIC THROUGH PUBLIC AWARENESS CAMPAIGNS WHILE MAKING SAFE CHOICES AND THEN FINALLY PARTNERING WITH PUBLIC SAFETY AND COMMUNITY ORGANIZATION, SO WE'RE REALLY GRATEFUL FOR COLLABORATIONS FOR PARTNERS AND ORGANIZATIONS FOR THIS ENDEAVOR. NEXT SLIDE. THE COMPLEX AND CHANGING NATURE OF THE OVERDOSING EPIDEMIC SHOWS THE COMPREHENSIVE APPROACH AND WE LIKE TO USE DATA TO FORM ACTION, SO THIS IS CALLED OVERDOSE DATA TO ACTION AND IT SUPPORTS 66 RECIPIENTS, 47 STATES, PUERTO RICO AND DC AND 60 COUNTIES AND OBTAINING MORE TIMELY DATA ON--GIVEN THE IMPACT COVID-19 HAS HAD, WE ANNOUNCED A FOURTH YEAR OF FUNDING FOR THESE RECIPIENTS AND LIKE TOM MENTIONED WE ALSO RECEIVED ARK DITIONAL LANGUAGE TO BE ABLE TO ADDRESS STIMULANTS AND POLYSUBSTANCE USE AND WE'VE MODIFIED THAT IN OUR PROGRAM AS WELL. NEXT SLIDE. SO I WANTED TO HIGHLIGHT DATA THAT HOPEFULLY IF YOU'RE NOT FAMILIAR WITH, YOU CAN USE IN THE WORK THAT YOU DO. THE SURVEILLANCE COMPONENT OF OUR GRANT PROGRAM REALLY AIMS TO HELP RECIPIENTS WHICH IS TIMELY COMPREHENSIVE AND ACTIONABLE DATA AND WE SUPPORTED TOCKICOLOGY TESTING, MEDICAL EXAMINER, CORONER REPORTS TO REALLY HAVE MORE ROBUST DATA AROUND CIRCUMSTANCES AND TESTING RELATED TO FATAL OVERDOSES AND THESE DATA ENHANCEMENTS ASSIST US IN IDENTIFYING LOCAL PUBLIC HEALTH ALERT AND PREVENTION STRATEGIES SUCH AS ROB EDUCATIONAL RESPONSES TO SPIKE. AN EXAMPLE OF THIS IS THE MARYLAND OVERDOSE FATALITY REVIEW TEAM USE THESE DETAILS DATA TO CONDUCT CONFIDENTIAL DATA CASE REVIEWS OF OVERDOSE TO PREVENT FUTURE DEATHS AND THE TEAMS HAVE BEEN ABLE TO IDENTIFY ADDITIONAL OPPORTUNITIES FOR PREVENTION AS WELL AS GAPS IN THE ASKS AND AREAS FOR INCREASED COLLABORATION AMONG STAKEHOLDERS AT THE LOCAL LEVEL. NEXT SLIDE. AND WE HAVE ALSO ACCELERATED NONFATAL DATA. WE IDENTIFY GRANT FUNDS TO DO THIS AND NOW MORE THAN 40 SITES ARE REPORTING DATA WITHIN 2-4 WEEKS FOR OUR NONFATAL OVERDOSES IN COMMUNITIES AND STATES. THIS,A LOWS COMMUNITIES TO REALLY USE THAT DATA TO PIVOT AND ADDRESS SURGES AS THEY SEE THEM. OHIO USED THIS TO DETECT ANOLLLIES AND HOW HAS AUTOMATED REPORT FUNCTIONS THAT LOCAL HEALTH DEPARTMENTS USE TO QUICKLY INFORM ACTION AND THE HEALTH DEPARTMENT ALSO DEVELOPED GUIDANCE AT THE LOCAL HEALTH DEPARTMENT TO DEVELOP COMMUNITY RESPONSE PLANS TO INCREASES IN SUSPECTED DRUG OVERDOSE. NEXT SLIDE. AND SO WE WOULD LIKE TO BE ABLE TO USE THAT DATA TO HAVE TOOLS THAT THE PUBLIC CAN USE, THIS IS ON OUR WEBSITE NOW CALLED FRED, THE FRAMEWORK FOR RECONSTRUCTING EMDEEMIO LOGICAL DISCIPLINARY MEDICARE AND MEDICAIDICS AND IT WAS USED ORIGINALLY TO STIMULATE INFECTIOUS DISEASE EPIDEMICS AND AFTER A 2 YEAR INVESTMENT FROM CDC, WE ARE LOOKING AT PREVENTION AND MITIGATION EFFORTS AT STATE AND COUNTY LEVELS AROUND OVERDOSE AND YOU CAN SEE ON THE LEFT OF THE SLIDE, AND THE SIMULATION FOR ALGENERATEDY COUNTY, OVER 4 YEARS NO INTERVENTION, THAT WILL BE AN ESTIMATED 68,000 OPIOID USE DISORDER CASES AND AROUND 2700 OVERDOSE DEATHS. AND THENOT RIGHT SIDE, CAN YOU SEE WHAT HAPPENS IF THERE'S INCREASE IN NALOXOE OVER AND RESULTING IN DECREASE IN CASES AND IN DEATH. THIS SIMULATION ARROWS TO YOU INCREASE THE AMOUNT OF NALOXONE, AND MOUD AT DIFFERENT LEVELS TO SEE WHAT THE IMPACT WOULD BE. NEXT SLIDE. WE REALLY TRY TO ENGAGE DIFFERENT COMMUNITY PARTNERS AND 1 OF THOSE GROUPS WE HAVE REALLY BEEN WORKING WITH CLOSELY LATELY IS PUBLIC SAFETY THROUGH DATA SHARING AND WE CAN SEE WHAT SOME OF THE DIFFERENT DRUG SEIZURES ARE SO WE CAN INFORM COMMUNITIES. REALLY WORKING ON EDUCATING HARMS OF AMONG CRIMINAL JUSTICE POPULATIONS AND TRAINING AROUND MOUD BEFORE RELEASE TO REALLY MAKE SURE THAT WE'RE PREVENTING THOSE OVERDOSES AND DOING TRAINING ACTIVITIES ON THINGS LIKE COMPASSION FATIGUE AND RISK REDUCTION AS WELL AS INCORPORATING THEIR EFFORT AND POST OVERDOSE OUTREACH. WE WORK WITH SOME OF OUR PARTNERS AS WELL TO DEVELOP A DOCUMENT THAT'S NOW AVAILABLE ON OUR WEBSITE ON HARM REDUCTION ON ACTIVITIES DURING COVID AND SOME OF THE INNOVATIONS THAT A LOT OF LOCAL ORGANIZATIONS HAVE IMPLEMENTED. NEXT SLIDE. AND JUST LOOK SIDE AS WE WELCOMER WITH CDC AND THE RAPID RESPONSE FRESHMAN AND THIS IS AN INTERAGENCY COORDINATED EFFORT TO REDUCE OVERDOSE RISK AMONG PATIENTS IMPACTED AND REALLY USES, WHEN LAW ENFORCEMENT COMES IN THAT MIGHT DISRUPT ACCESS TO PRESCRIPTION OPIOIDS OR MOUD, THESE COORDINATORS WORK IN CONJUNCTION WITH LOCAL PRACTITIONERS TO REALLY BE ABLE TO LINK PATIENTS TO CARE AND REDUCE SOME OF THESE UNINTENDED CONSEQUENCES SO NOW WE'RE WORKING WITH THE NEW MEXICO ECHOITUTE FOR RAPID RESPONSE TRAINING AND SUPPORT FOR TA SO THE LOCAL PROVIDERS HAVE THE SKILLS AND TOOLS NECESSARY TO TREAT PATIENTS ON OPIOID TEPENDENT PATIENT FIST THERE'S A DISRUPTION IN CARE. NEXT SLIDE. THIS SLIDE HAS BEEN THE 2016 GUIDELINE FOR STRIEBING OPIOID FOR CHRONIC PAIN AND WITHIN THAT GUIDELINE WE DID SAY THAT AS NEW EVIDENCE EMERGED WE WOULD CONSIDER UPDATING OUR GUIDELINE. WE FUNDED THE AGENCY FOR HEALTHCARE RESEARCH AND QUALITY CONDUCT SYSTEMATIC REVIEWS AND PUBLISHED SEVERAL NEW REVIEWS AND BASED ON THAT EVIDENCE WE ARE UNDERGOING AN UPDATE OF OUR GUIDELINE, WE'VE ENGAGED THE COMMUNITY TO DATE IN 2-POINTS OF ENGAGEMENT, 1 IS THROUGH PUBLIC COMMENT PERIOD AND THE OTHER IS A SECOND FEDERAL NOTICE WHERE WE DID INDIVIDUAL FOCUS GROUPS AND MEETINGS WITH PATIENTS WITH ACUTE OR CHRONIC PAIN, FAMILY MEMBERS AND CAREGIVERS AND CLINICIANS WHO CARE FOR PATIENTS TO REALLY HELP INFORM IN UPDATED DEVELOPMENT. SO STAY TUNED FOR MORE ON THIS. WE WILL CERTAINLY ENGAGE YOU ALL AND SEND OUT NOTICES, AND WHEN THERE'S OPPORTUNITY TO COMMENTOT GUIDELINE ITSELF, IT'S STILL CURRENTLY IN DRAFT GUIDANCE BUT THERE WILL BE OPPORTUNITY FOR FULL PUBLIC COMMENT. NEXT SLIDE. WE ALSO HAVE THE RX AWARENESS CAMPAIGN AND WHAT I WANTED TO HIGHLIGHT IS WHATY WOO WILL BE DOING. WE HAD UPDATED THIS CAMPAIGN TO REALLY FOCUS ON GROUPS LIKE REGNANT WOMEN, AND VETERANS AND YOUNGER ADULTS BUT GIVEN A LOT OF THE CHANGE TO FENTANYL AND POLYSUBSIDIARY CONSTITUTES WE'RE NOW GOING TO HAVE AN UPDATED CAMPAIGN TO FOCUS ON TOOLS THAT COMMUNITIES CAN USE TO HIGHLIGHT THESE CHANGES. NEXT SLIDE. AND THE DRUG FREE COMMUNITIES, WE HAVE PARTNERED WITH ONDCP AND WE ARE NOW DOING THE DAY-TO-DAY MANAGEMENT ROLL ON THIS, IF YOU ARE INTERESTED IN WORKING WITH A DRUG FREE COALITION IN OUR AREA, WE HAVE A SURGICAL LIST OF FUNDED ORGANIZATIONS BY CITIES ON OUR WEBSITE, THESE ARE 700 COMMUNITY COALITIONS, REALLY FOCUS ON PRIMARY PREVENTION AND I KNOW THIS WILL BE A GREAT, I THINK SIN EMBRYONIC STEMY WITH NIH HEAL IF NOT ALREADY ENGAGED. NEXT SLIDE. I DID JUST WANT TO HIGHLIGHT SOME OF OUR RECENT PUBLICATIONS AROUND THE OVERDOSE EPIDEMIC. AS YOU ARE AWARE IT WAS INCREASED IN PREPANDEMIC AND RELEASE A HEALTH ADVISE ROY NOTICE IN DECEMBER ON EXPANDING DISTRIBUTION AND USE OF NALOXONE, AND EXTENDING TREATMENT FOR SUBSTANCE USE AND ISHT VENING EARLY FOR THOSE INDIVIDUALS HIGH RISK OF OVERDOSE GIVEN THAT WE'RE SEEING CONTISSUE AND MACROPHAGES NATION IN CO-USE AND STIMULANTS AND COCAINE USE WITH FENTANYL. NEXT SLIDE. AND THESE ARE JUST SOME OF THE ACTIONS THAT WE HAVE WORKED WITH OUR GRANTEES TO REALLY UPDATE AND RESPOND TO THE CHANGE IN EPIDEMIC. TOM HIGHLIGHTED WE ARE DELIGHTED TO PARTNER WITH SHAM ON EXTENDING FEDERAL FUNDING TO ALLOW THE UTV TESTING WE ALLOWED A LOT OF THE FLEXIBILITIES WITH GRANTEES ON THINGS LIKE DRIVE-THROUGH AND NALOXONE, AND ALSO SHIFTING TO VIRTUAL. NEXT SLIDE. AND THIS IS JUST A TAKE AWAY FOR YOU ALL WITH OUR RECENT PUBLICATIONS, AND LAST SLIDE. I JUST WANT TO SAY THIS PAST YEAR WAS NOT WHAT WE HAD ANTICIPATED ACROSS THE BOARD, BUT I THINK THE PANDEMIC HAS ALLOWED ALL OF US TO RESPOND TO DIFFERENT CHALLENGES AND WHILE THERE'S STILL A LONG ROAD OF RECOVERY, I KNOW THAT WORKING TOGETHER WITH NIH SAMHSA, FDA AND ALL OF THE GRANTEES, THAT WE WILL BE ABLE TO PREVENT DRUG OVERDOSE AND THE IMPACTS OF SUBSTANCE ABUSE. THANK YOU. >> THANK YOU DR. HOURY, THAT WAS VERY HELPFUL AND INFORMATIVE AND NOW, I WOULD LIKE TO TURN TO DR. WOODCOCK. >> THANK YOU DR. TABAK, CAN YOU HEAR ME? I'M GETTING AN ODD MESSAGE ON YOUR SCREEN. >> YES I AM ABLE TO HEAR YOU, I AM SEEING NODDING HEADS. >> GREAT. VERY GOOD. THANK YOU FOR INVITING ME TO JOIN TODAY'S DISCUSSION, THE HEAL INITIATIVE IS AN IMPORTANT EFFORT TO HELP'D VANCE SOLUTIONS TO THE NATION'S OPIOID CRISIS AND OF COURSE I'VE BEEN SUPPORTIVE SINCE THE BEGINNING. IT REALLY UNDERSCORES THE PUNISHES OF COLLABORATION IN THIS AREA, BOTH ACROSS GOVERNMENT AS WE'RE JUST HEARING, AND WITH PATIENTS AND THEIR FAMILIES. COLLABORATION AND COMMUNICATION REALLY ARE OBVIOUSLY MORE NEEDED THAN EVER WITH THE ADDITIONAL CHALLENGES POSED BY THE SARS-COV-2 VIRUS. THE RESULTING PUBLIC HEALTH EMERGENCY DISRUPTED ALMOST EVERY ASPECT OF OUR LIVES AND UNFORTUNATELY, IT DID NOT MAKE OTHER PUBLIC HEGHT CHALLENGES LIKE THE OPIOID CRISIS VANISH. WE'RE ALL TOO FAMILIAR WITH THE LATEST MEMBERS SHOWING THE RECEIPT INXREES IN OVERDOSE RELATED DEATHS. PRESCRIPTION DRUGS TO INCREASINGLY INVOLVES AS WE JUST HEARD OTHER ILLICIT DRUGS INCLUDING SOME VERY POTENT VERSIONS OF FENTANYL AND ANALOGUES OF FENTANYL. AND AS YOU KNOW WE ARE NOW SEEING WIDE SPREAD USE OF STIMULANTS, PARTICULARLY METHAMPHETAMINE IN COMBINATION WITH OPIOID AND RECOGNIZE THERE'S AN URGENT NEED FOR REVERSAL OF FOR STIMULANT OVERDOSE AND STIMULANT USE DISORDER AND WE'RE WORKING HARD TO ACCELERATE DEVELOPMENT IN THIS FIELD. ONE QUESTION IS HOW MUCH OF THIS RECENT INCREASE IN DUE TO THE DOCUMENTED PSYCHOLOGICAL STRESS CAUSED BY IMPOSED ISOLATION DURING THE PANDEMIC. AND A PARTICULAR AREA OF CONCERN FOR US WAS THE IMPACT OF INCREASED ISOLATION ON THOSE BATTLING THE BURDEN OF SUBSTANCE USE DISORDER. WE LOOK CLOSELY AT WHAT WE COULD DO TO SUPPORT EFFORTS TO MAINTAIN TREATMENT AND PERSONAL CONTACT FOR MEMBERS OF THESE VULNERABLE GROUPS. AS 1 INDIVIDUAL IN LONG RECOVERY TOLD US, THE OPPOSITE OF ADDICTION IS CONNECTION, NOT ISOLATION. TO PROVIDE SUPPORT FOR THOSE SEEKING TREATMENT WE EXTENDED OUR LONG STANDING COMMITMENT TO SUPPORT DIGITAL HEALTH IN PART TO OUR RECENTLY ESTABLISHED DIGITAL CENTER OF HEALTH EXCELLENCE. AS WE'VE LEARNED THE AVAILABILITY OF DIGITAL HEALTH DEVICES LIKE MOBILE MEDICAL APPS CAN PLAY A UNIQUE AND IMPORTANT ROLE IN TREATMENT EFFORTS THIS CAN BE VALUABLE IN KEEPING INDIVIDUALS ENGAGED IN THEIR MEDICATION ASSISTED TREATMENT PROGRAMS AND PROVIDING CLINICIANS WITH NEW WAYS TO INTERVENE AND TO SUPPORT TREATMENT AND WE'VE SEEN SIGNIFICANT PROGRESS RECENTLY IN ADVANCING USE OF TELEHEALTH AND HEALTH INFORMATION TECHNOLOGY AS WELL AS A REGULATORY EXPANSION OF TELEHEALTH, ANY PRESCRIBING TO INCLUDE TREATMENT OF OPIOID USE DISORDER. AND WE REALLY APPLAUD THE IMPORTANT WORK TO DRIVE THESE EFFORTS BY OUR FEDERAL COLLEAGUES INCLUDING DEA, SAMHSA AND CMS. FDA CENTER FOR DEVICES PERMITTED MARKETING THE FIRST MOBILE MEDICAL APPLICATION TO HELP TREAT SUBSTANCE USE DISORDERS IN 2017. THE RESET APPLICATION IS INTENDED TO BE USED WITH OUTPATIENT THERAPY TO TREAT ALCOHOL, CO TIANYL, MARIJUANA AND STIMULANT SUDs. JUST A FEW YEARS AGO, THE DEVICE CENTER LAUNCHED AN INNOVATION CHALERG TO HELP SPUR DEVELOPMENT OF MEDICAL DEVICES INCLUDING DIAGNOSTIC TESTS AND DIGITAL HEALTH TECHNOLOGIES TO HELP COMBAT THE OPIOID CRISIS. EIGHT PARTICIPANTS WERE SELECTED AND THE DEVICES INCLUDED THOSE INTEBDED TO PREDICT THE USE OF OUD, DETECT OPIOID OVERDOSE, DISPENSE MEDICATION AND PRACTICES VIED TREATMENT ALTERNATIVES FOR PAIN THAT ARE NONOPIOID. ANOTHER AREA FOR FOCUS FOR THE FDAs ARE CONTINUING EFFORT TO DEVELOP A BETTER FRAMEWORK FOR MEDICAL PRESCRIBING OFOIDS AND REDUCE THE ACCESSIVE NUMBER OF PRESCRIPTIONOID DRUGS THAT STILL FLOOD THE MARKET. PRESCRIBERS AND PATIENTS NEED TO BE FULLY INFORMED ABOUT RISKS AND BENEFITS OF THESE DRUGS BUT WE ALSO HAVE TO MAKE SURE THERE'S ALIGNMENT BETWEEN THE PATIENTS CLINICAL NEED AND THE PRESCRIPTION. WE CONTINUE TO WORK WITH OUTSIDE GROUPS TO DEVELOP EVIDENCE-BASED GUIDELINES TO HELP IEE, AUDIENCE DENTIFY AND ADDRESS GAPS AND UNDERSTANDING AND SUPPORT MORE APPROPRIATE PRESCRIBING PRACTICES. THESE GUIDELINES ARE VERY SPECIFIC FOR EXAMPLE, WORKING WITH THE ORAL SURGEONS COMMUNITY ON THIRD MOLAR EXTRACTION FOR EXAMPLE SO THAT WE CAN TRY TO GET TO BEST PRACTICES AND SOME OF THESE AREAS WHERE OPIOIDS ARE STILL WIDELY USED PARTICULARLY IN ADOLESCENTS. WE ALSO CONTINUE TO STRENGTHEN THE CONTENT OF THE DRUG LABEL ITSELF. LAST SEPTEMBER WE ISSUED DRUG SAFETY COMMUNICATION ANNOUNCING THE REQUIREMENT THAT THE BOX WARNING WILL BE UPDATED FOR ALL BENZO DIAZ PENES AND THIS FEBRUARY WE INSTITUTED CLASS WIDE SAFETY LABELING CHANGES FOR THE BENZO-LABEL TO INCLUDE MORE ABOUT THE SERIES RISKS ASSOCIATED WITH THESE MEDICINES. WE ALSO ISSUED A SAFETY LABELING CHANGE AND DRUG SAFETY COMMUNICATION ANNOUNCED THE REQUIREMENT THAT DRUG MANUFACTURES WERE ALL OPIOID PAIN RELIEVERS AND MEDICINES TO TREAT OUD THAT ARE OPIOID LIKE MUST ADD NEW RECOMMENDATIONS ABOUT NALOXONE. --THE NEED FOR NALOXONE WHEN OPIOID ARE GIVEN AND ASSESS EACH PATIENT'S NEED FOR NALOXONE WITH WHEN OPIOID PAIN RELIEVERS OR CERTAIN MEDICINE TO TREAT OUD ARE BEING PRESCRIBED OR RENEWED. FDA APPROVED 3 DIFFERENT FORMS OF NALOXONE, IRBING, AUTOINJECTOR AND NAISAL SPRAY ALL OF WHICH ARE APPROPRIATE FOR COMMUNITY USE AND WE CONTINUE TO SUPPORT EXPANDING ACCESS TO THIS LIFE SAVING TREATMENT. WE ARE CONTINUING TO WORK ON OF COURSE OVER THE COUNTER VERSIONS WHICH MUST RELY UPON MANUFACTURES FOR SUBMISSION. ON THE TREATMENT FRONT WE'VE PUBLISHED 2 GUIDANCES FOR INDUSTRY, THE FIRST IS CALLED OPIOID USE DISORDER END POINTS FOR DEMONSTRATING EFFECTIVENESS FOR DRUGS FOR TREATMENT, AND IT'S INTENDED TO HELP RESPONSESSORS DEVELOP DRUGS FOR TREATMENT OF OUD BY IDENTIFYING CLINICAL END POINTS THAT WOULD BE ACCEPTABLE FOR DEMONSTRATING DRUG EFFECTIVENESS. THE SECOND FINALIZED NEW POLICY TO ENCOURAGE WIDE SPREAD INNOVATION AND DEVELOPMENT OF NEW AND TREATMENTS FOR AND I WANT TO BRIEFLY MENTION OUR WORK ON RISK EVALUATION AND MITIGATION STRATEGIES ALSO KNOWN AS REMs FOR VARIOUS OPIOID ANALGESICS. WE KNOW THE IMPORTANT ROLE THAT REMs CAN PLAY IN PROVIDING PATIENTS AND PRESCRIBERS WITH,A DITIONAL KNOWLEDGE AND SAFETY INFORMATION. WE NEED TO CONTINUE TO ENCOURAGE PARTICIPATION IN THESE PROGRAMS AND WHERE POSSIBLE, LINK IT WITH OTHER TYPES OF TRAINING ON TREATING PAIN AND OUD. WE WILL ALSO CONTINUE TO EXPLORE WAYS TO BROADEN ACCESS TO TRAINING AND WORK WITH OUR FEDERAL PARTNERS TO PROMOTE AND IMPROVE TRAINING PARTICIPATION IN BOTH AREAS. WE'RE COMMITTED TO INCREASING ACCESS TO MEDICAL TREATMENT FOR OUD THAT HAVE DEMONSTRATD SAFETY AND EFFICACY. AND WE'RE WORKING WITH OUR GOVERNMENT PARTNERS TO ADDRESS BARRIERS TO ACCESS. PRIORITIZING EDUCATION AND TRAINING CAN HELP ADDRESS ISSUES OF STIGMA, AMONG PROVIDERS, INCREASE AVAILABILITY OF TREATMENT, AND BRING OUD TREATMENT CLOSER IN LINE WITH HOW OTHER CHRONIC DISEASES ARE TREATED. FINALLY, I WANT TO MENTION THAT EVEN AS WE WORK TO FIND NEW TREATMENT, STRENGTH AND SAFETY MEASURES AND ULTIMATELY LOWER THE NUMBER OF OPIOID AND STIMULANT OVERDOSE DEATHS WE CONTINUE OUR RIGGOUS EFFORTS TO CRACK DOWN ON THE ILISOTOPEIT MARKET FOR OPIOID AND ILLEGAL DRUGS AND SECURE THE SUPPLY CHAIN FOR LEGITIMATE MEDICATIONS INCLUDING OPIOIDS. THIS INCLUDES COMBATING ILLEGAL ONLINE SALES OF OPIOIDS AND OTHER CONTROLLED SUBSTANCES AS WELL AS INCREASING OUR ENFORCEMENT INTERDICTION WORK TARGETING ILLEGAL, UNAPPROVED COUNTERFEIT AND POTENTIALLY DANGEROUS PRODUCTS THAT ARE SHIPPED ILLEGALLY THROUGH INTERNATIONAL MAIL FACILITIES INTO THE UNITED STATES. SO, FDA HAS A BROAD RANGE OF ACTIVITIES, FROM ALL THE WAY FROM DRUG DEVELOPMENT FOR ALTERNATIVES TO TREATS PAIN AS WELL AS TREATMENT FOR OPIOID USE DISORDER AND OTHER SUDs, ALL THE WAY TO INTERDICTION OF THESE SUBSTANCES INTO THE UNITED STATES AND IN THAT WE WORK WITH ALL THE DIFFERENT FEDERAL AGENCIES. SO THANK YOU VERY MUCH AND I LOOK FORWARD TO OUR DISCUSSION. >> THANK YOU VERY MUCH DR. WOODCOOK AND I THINK ALL OF OUR BENEFITS ITED HAVE BENEFITED FROM THESE COMPREHENSIVE REVIEWS FROM THE 3 DIFFERENT AGENCIES. I GUESS, TO START THE CONVERSATION WE HAVE WITH US SEVERAL HUNDRED INVESTIGATORS, HEAL INVESTIGATORS AND I--THESE ARE ACTION ORIENTED PEOPLE THAT'S THE THING THAT IS REALLY THEY WANT TO RAPIDLY MOVE EVIDENT FROM THE BENCH TO THE BODY SIDE AS IT WERE. IF YOU IF I WOULD PLEASE ADDRESS HOW CAN THESE HEAL INVESTIGATORS BETTER ADDRESS THE NEEDS OF YOU, THE FEDERAL POLICY MAKERS IN YOUR RESPECTIVE DOMAINS TO EFFECT THAT MORE RAPID TRANSITION FROM RESEARCH EVIDENCE TO PRACTICAL TANGIBLES TO HELP OUR PATIENTS. SO, I DON'T KNOW WHO WOULD LIKE TO TAKE THAT 1 FIRST? >> I CAN START IT, I'M SURE MY COLLEAGUES WILL HAVE SOME COMMENTS. >> --PROVIDE GUIDANCE TO THE FIELD SO WE'RE IN THAT ACTION ORIENTED SPACE, TOO, AND TRY TO GET OUR GRANTEES TO BE USING THE MOST UPTO DATE AND BEST EVIDENCE THAT EXISTS. OFTEN TIMES, YOU KNOW WE ARE--WE RELY ON FOLKS SUCH AS THE HEAL INVESTIGATORS FOR INFORMATION ABOUT WHAT'S HAPPENING IN THE FIELD AND I THINK, YOU KNOW IF THEY CAN SHARE THAT WITH US, ON A REGULAR BASIS THEN I KNOW WE HAVE--WE BENEFIT FROM REGULAR CALLS WITH OUR COLLEAGUES AT NIDA AS I MENTIONED, DR. HAVE, OLKOW AND SEVERAL OTHER FOLKS JOINING US TODAY BUT HAVING THAT INFORMATION THAT WE CAN THEN GET BACK OUT TO GRANTEES TO SHARE MORE BROADLY, I THINK CAN BE REALLY, REALLY HELPFUL FOR US AND WE WOULD WANT TO BE ABLE TO KNOW WHAT'S HAPPENING OUT IN THE FIELD ON A REGULAR BASIS. FEDERAL GOVERNMENT, YOU KNOW IS GOING TO COME AS A SURPRISE TO ALL OF YOU IS NOT TERRIBLY NIMBLE AND SO, THE MORE INFORMATION WE HAVE, THE QUICKER WE CAN START TO PROCESS THAT, SO THAT WE CAN GET IT OUT TO THE FIELD IN AIAN QUICKER WAY SO THAT IT CAN INFORM WHAT THESE GRANTEES ARE DOING. GRANTEES ON THE OTHER HAND CAN BE RATHER NIMBLE. THEY DON'T HAVE--YOU KNOW TRADITIONALLY THEY DON'T HAVE THE SAME KIND OF BUREAUCRATIC HOOPS TO JUMP THROUGH IN LOCAL ESPECIALLY LOCAL COMMUNITY BASED ORGANIZATIONS AND SO, THEY CAN TYPICALLY TURN AROUND AND CHANGE AND PIVOT SOME OF THE STUFF THEY'RE DOING IF YOU GUYS ARE FINDING OUT THAT WE SHOULD BE DOING SOMETHING, 1 PARTICULAR WAY VERSUS ANOTHER, IF SOMETHING IS HAPPENING IN THE FIELD RIGHT NOW, WE WOULD BENEFIT FROM KNOWING THAT SO WE COULD GET THAT INFORMATION AND PUSH IT OUT TO GRANTEES. >> GREAT. THANK YOU. VERY HELPFUL WOULD ANY OF THE OTHER PANEL MEMBERS CARE TO ADDRESS THAT. >> WELL, I WOULD. THIS IS JANET. SO MY COLLEAGUE ROB KALIFF WHO IS A FORMER FDA COMMISSIONER ONCE WROTE A PAPER SHOWING THAT IN CARDIOLOGY, WHICH IS 1 OF THE MOST STUDIED AREAS IN MEDICINE ONLY 5% OF THE CLINICAL GUIDELINES WERE EVIDENCE-BASED. AND THE 95% OF THE REST OF THE WERE IN EXPERT OPINION AND OF COURSE, THE FIELD OF USE DISORDERS AND BEHAVIORIAL DISORDERS, AND SO FORTH IS EVEN--HAS BEEN LESS STUDIED AND LESS EVIDENCE-BASED EVEN FOR INTERVENTIONS. SO, I WOULD PLEA THAT EVERYONE REALLY WORK ON MAKING SURE THAT SOLID EVIDENCE IS GENERATED TO GIVE PRACTICE RECOMMENDATIONS, NOT ONLY FOR THE TREATMENT OF PAIN IS A REALLY IMPORTANT 1 BECAUSE WE HAD THE PAIN MOVEMENT, EVERYONE WAS URGED TO TREAT PEOPLE WITH PAIN, RIGHT? AND PRETTY SOON CAME ALONG THAT SAID WE SHOULDN'T GIVE YOU NSAIDS BECAUSE THEY'LL GIVE YOU HEART ATTACKS AND GI BLEEDS AND TYLENOL MIGHT GIVE YOU LIVER FAIL AND YOU ARE PRETTY SOON PEOPLE WERE JUST WRITING LEFT AND RIGHT'RE RIGHT FOR THESE OPIOIDS. SO I THINK WE STILL DON'T HAVE SPECIFIC UNDERSTANDING OF THE TREATMENT OF PAIN. YOU KNOW THE CDC GUIDELINE I THINK DID A GREAT JOB BUT IT WAS VERY GENERAL, OKAY, IT'S NOT ABOUT THIS PARTICULAR CONDITION AND WHAT IS THE BEST TO TREAT IT. SO I WOULD SAY THAT IN ALL AREAS OF THIS FIELD, WHICH MUCH OF WHICH HAS BEEN PERMINATEIATED BY THIS STIGMA. THERE'S A LACK OF EVIDENCE AND SO WHAT IS BEING DONE IS TREMENDOUS WORK AND JUST NEEDS TO BE REALLY STIMULATED SO THAT WE HAVE EVIDENCE TO GUIDE BOTH RECOMMENDATIONS, AS WELL AS PRACTICE. >> THANK YOU SO MUCH. DEBWOULD YOU LIKE TO ADD? >> YES, I WOULD AGREE AND I WOULD SAY WITH EVOLVING EPIDEMIC, WE WILL HIT THE RECORD NUMBER OF DEATHS EVER, THIS IS THE TIME WHERE WE NEED ALL OF THE RESEARCHERS AND PRACTICE RESEARCH IGDZERS TO BE REALLY WORKING WITH US AROUND INNOVATIONS AND STRATEGIES. WE KNOW THERE'S VERY LIMITED EVIDENCE ON HOW DO WE TREAT PEOPLE WHO NEED STIMULANTS. WE ARE LOOKING TO YOU ALL TO GUIDE US ON THAT AS WE RECEIVE MORE POLYSUBSTITUTIONS, AND THOSE WITH FENTANYL HOW DO WE TRACK THAT? GET THE MESSAGE OUT? AS YOU'RE DEVELOPING THESE INNOVATIVE INTERVENTIONS IN THE FIELD WE NEED TO BE ABLE TO SHARE THAT ACROSS THE STATE AND WITH OUR GRANTEES SO IT'S LIKE JANET SAID, TOO WE NEED A LOT MORE OF THE RESEARCH TO DRIVE-- >> OF ALL OF OUR HEAL INVESTIGATORS HERE THEY WOULD WANT TO KNOW FROM YOU WHAT SPECIFIC ADDITIONAL RESEARCH DO YOU NEED THEM TO CONDUCT GOING FORWARD? YOU MENTIONED POLYUSE AND SO FORTH AND BEST DELIVERY SYSTEMS AND WHAT WORKS AND HOW TO DISSEMINATE AND THAT'S A GREAT START BUT WHAT IN ADDITION CAN WE TAKE ADVANTAGE OF THIS OPPORTUNITY TO SPEAK DIRECTLY WITH THIS LARNL NUMBER OF INVESTIGATORS SO THAT THEY GET A BETTER SENSE OF SOME OF THE REAL WORLD PROBLEMS THAT EACH OF YOU FEEL WE NEED THE EVIDENCE FOR TO HELP MOVE THE AGENDA FORWARD. SO, I DON'T KNOW WHO WOULD LIKE TO BEGIN FIRST? >> I'LL JUMP IN AGAIN, IF YOU GUYS WOULD LET ME. THIS WILL CAN AM AS NO SURPRISE TO YOU BUT I OBVIOUSLY THINK TAKEN--THEY WE NEED MORE EVIDENCE ON RECOVERY SUPPORT SIDE OF THE CONTINUUM. OF COURSE DEB'S ABSOLUTELY RIGHT, WE NEED MORE TREATMENTS THAN INTERVENTIONS FOR STIMULANTS AND FOR EMERGING SUBSIDIARY STANCES BUT WE KNOW A LOT ABOUT TREATMENT AND WHAT WORKS FOR PEOPLE, AND THESE INTERVENTIONS HAVE BEEN STUDIED A LOT MORE THAN WE KNOW ABOUT INTERVENTIONS FOR RECOVERY SUPPORT AND GIVEN THE FACT THAT THIS IS NOT AN ACUTE CONDITION, THIS IS A CHRONIC CONDITION THAT SOMEBODY HAS OVER A PERIOD--OVER THEIR LIFETIME, PARTICULARLY AND IT TAKES 5 YEARS FOR SOMEBODY TO GET TO THE 15% REMISSION PARK. YOU NEED TO OBTAIN A LOT MORE EVIDENCE ABOUT WHAT WORKS IN RECOVERY. I REMEMBER SPEAKING AT A PRESS CONFERENCE 1 YEAR, IT HAPPENED IN SEPTEMBER EVERY YEAR TO KICKOFF RECOVERY MONTH AND I WAS THE RECOVERY SPEAKER AT IT AND IT WAS GREAT, WE WERE USING THE NISDA DATA, THE NATIONAL SURVEY - DRUG HIEWS AND HEALTH DATA ANDY COULD TELL YOU WHAT DRUG IS BEING USED ON WHAT TREAT CORNER AT WHAT TIME IN THE UNITED STATES, YOU KNOW TO A LOT OF SPECIFICITY BUT WE COULDN'T TELL YOU HOW PEOPLE WERE FINDING AND SUSTAINING THE RECOVERY OVER THE LONG-TERM AND I THINK EVIDENCE AROUND THAT WOULD REALLY BE HELPFUL, IT WOULD HELP US NOT ONLY IMPROVE PEOPLE'S LIVES LIKE MINE AS BEEN IMPROVED BUT IT WILL ALSO HELP US FIGHT TO GET THE KINDS OF RESOURCES AND PUBLIC POLICIES IN PLACE THAT WILL ADVANCE THESE TYPES OF INTERVENTIONS FOR THE LONG-TERM BECAUSE I'M--YOU KNOW I THINK A LOT OF US ARE PRETTY FRUSTRATED, YOU KNOW THE NUMBERS ARE CONTINUING TO RISE, THIS IS REALLY SAD IN TERMS OF THE LIVES WE'VE LOST, THE FAMILIES THAT HAVE BEEN DESTROYED AND WHOLE COMMUNITIES HAVE BEEN DESTROYED BECAUSE OF THE EPIDEMICS AND WE'RE SEEING THIS REVOLVING DOOR SOMETIMES OF PEOPLE BACK INTO TREATMENT BECAUSE THEY DON'T GET THE PSYCHOSOCIAL AND RECOVERY SUPPORTS THAT THEY NEED TO SUSTAIN THEIR RECOVERY FOR THE LONG-TERM. AND SO FOR ME, THAT WOULD BE MY REQUEST TO THE INVESTORS, PLEASE HELP US DEVELOP MORE AND THIS IS MY REQUEST TO NIH, TOO, PLEASE HELP US DEVELOP MORE EVIDENCE AROUND RECOVERY SUPPORTS. WE HAVE A--WE HAVE AN ENTIRE CHAPTER IN THE SURGEON GENERAL'S REPORT IN ALCOHOL RELATED TO RECOVERY SUPPORT AND THE LAST THING IN THAT CHAPTER SAYS WE NEED MORE RESEARCH SO PLEASE HELP US GET THAT RESEARCH. >> THANK YOU VERY MUCH. JANET YOUR COMMENTS ON THIS. >> I CERTAINLY AGREE WHOLE HEARTEDLY. WE FOCUS ON THE OVERDOSE STATS BUT ONCE PEOPLE GET INTO RECOVERY HOW ARE THEY SUSTAINED? IT IS A CRITICAL PIECE IN PREVENTING RELAPSE AND THEN DEATH FROM OVERDOSE AND DESTRUCTION AGAIN OF PEOPLE'S LIVES, SO, I COULDN'T AGREE MORE, I THINK THIS WHOLE AREA HAS BEEN HELD BACK BECAUSE OF THE STIGMA ASSOCIATE WIDE IT AND WE HAVE TO GET OVER THIS AND TREAT IT AS A CHRONIC ILLNESS AND TREAT IT THROUGH THE ENTIRE TRAJECTORY AND LIFE SPAN OF THE ILLNESS, ALL RIGHT, RATHER THAN SAYING OH WELL WE GAVE YOU BUPRENORPHINE AND YOU'RE OKAY NOW AND YOU KNOW, THAT'S IT. ON THE OTHER HAND FROM THE FDA SIDE, I THINK WE'RE STILL LOOKING AT THE INITIATION AND TRIGGERS FOR INITIATION AND 1 OF THOSE OF COURSE IS UCIBOLLITYY OR AVAILABILITY OF DIFFERENT SUBSTANCES AND THEY'RE--I THINK WE NEED MORE EVIDENCE ON AND STRONG GUIDELINES BASED ON EVIDENCE ON THE USE OF OPIOID PAIN MEDICATIONS IN DIFFERENT SITUATIONS. YOU KNOW, WHEN I WAS A KID, AND I KNOW THIS SOUNDS LIKE A GEEZER TALKING ABOUT YOU I HAD AN ACCIDENT, I TORE MY ACL, TORE MY MCL AND WHAT DID THEY GAVE ME? THEY GAVE ME CRUTCHES. THAT'S WHAT THEY GAVE ME. RIGHT? NOW I'M NOT SAYING WE SHOULD BE THAT HEARTLESS IN THIS DAY AND AGE, BUT YOU KNOW WE DON'T HAVE TO GIVE PEOPLE 60 TABLETS WHEN THEY'RE IN A VULNERABLE STAGE OF DEVELOPMENT, WE DON'T HAVE TO DO THINGS LIKE THAT BUT WE NEED VERY STRONG VERY SPECIFIC GUIDANCE ON HOW TO TREAT PEOPLE WITH VARIOUS KINDS OF ACUTE PAIN IS A BIG PART OF THE SORT OF INTRODUCTION PROBLEM BECAUSE THESE DRUGS ARE SO UBIQUITOUS IN TREATMENT OF VARIOUS ACUTE PAIN INCIDENCE. SO A LOT OF FOCUS HAS BEEN ON CHRONIC PAIN, THAT'S A WHOLE DIFFERENT KIND OF PROBLEM THAT ALSO NEEDSA I LOT OF STUDY. SO THAT'S WHAT I THINK, I THINK THE WHOLE FIELD NEEDS CONTINUED RESEARCH IN MUCH MORE EVIDENCE-BASED AS I SAID EARLIER. >> GREAT. THANK YOU VERY MUCH. DEB, YOU ARE GOING TO GET THE LAST WORD ON THIS TOPIC, GO AHEAD, PLEASE? >> SO, I THINK IF I HAD A MAGIC WAND, I WOULD CERTAINLY GRANT TOM AND JANET THEIR WISHES AND MY THIRD WISH TO IT WOULD BE REALLY FOCUSING EVEN EARLIER ON PRIMARY PREVENTION, I THINK BY NOW WE'RE SEEING ALL THE NUMBER OF CHILDREN BEING EXPOSED TO DRUGS IN THE HOME, ALL THESE ADVERSE CHILDHOOD EXPERIENCES WE KNOW WILL PREDISPOSE PEOPLE TO POTENTIALLY SUBSTANCE MISUSE LATER SO HOW CAN WE LOOK AT INDIVIDUAL AND COMMUNITY LEVEL RESILIENCE TO PREVENT THIS EPIDEMIC FROM CONTINUING? >> GREAT. WELL, THANK YOU. SO SEVERAL OF YOU MENTIONED THE CHALLENGE THAT STIGMATIZATION PRESENTS, PARTICULARLY IN THIS SPACE. AND I WONDER IF YOU COULD OFFER YOUR REFLECTIONS ON HOW WE MIGHT WORK TOGETHER TO OVERCOME THIS, IT'S SUCH A CRITICAL PIECE OF THIS PUZZLE AND YET, HERE WE ARE STILL, YOU KNOW WE'RE ABLE TO MAP EVERY GENE IN A CELL AND SO FORTH BUT AT THIS VERY BASIC HUMAN REACTION IS NOT 1 WE'VE BEEN ABLE TO OVERCOME WOULD ANY OF YOU LIKE TO SHARE YOUR PERSPECTIVES ON THAT PLEASE? >> SURE. WE WOULD BE RICH IF WE WERE ABLE TO COME UP WITH THAT 1 DR. TABAK. I THINK IT WOULD SOLVE ALMOST EVERYTHING, IT WOULD SOLVE FOR PEOPLE BEING WILLING TO GET HELP A LOT EARLIER, IT WOULD SOLVE FOR DOCTORS BEING WILLING TO TREAT THIS DISEASE AND WE KNOW SO MANY, EVEN WITH THE RELEASE OF OUR NEW X-WAIVER PRACTICE GUIDELINES ISSUES THE CHALLENGE WILL BE TO GET DOCTORS TO AGREEN CELLS TO TREAT PATIENTS WITH OPIOID USE DISORDER. AND WE ALSO KNOW THAT YOU KNOW WE'RE DOING A LOT OF WORK IN THE OVERDOSE PREVENTION SPACE, WITH BUPRENORPHINE, OTHER KINDS OF ACTIVITIES, HARM REDUCK ACTIVITIES WHICH AREN'T NECESSARILY GETTING YOU KNOW, THEY'RE KEEPING PEOPLE FROM DYING WHICH IS REALLY IMPORTANT BECAUSE YOU CAN'T GET INTO RECOVERY IF YOU'RE DEAD BUT THEY'RE NOT NECESSARILY GETTING PEOPLE WELL. SO IT HAS THIS IMPACT THAT'S UNINTENDED CONSEQUENCE OF YOU KNOW ALMOST PERPETUATING THIS MYTH THAT PEOPLE DON'T GET BETTER FROM THESE DISORDERS. SO THAT'S 1 OF THE REASONS I SHARE MY RECOVERY STORY AS OFTEN AS I CAN BECAUSE I THINK IT'S IMPORTANT FOR PEOPLE TO HEAR THAT WE GET WELL. SO I THINK THAT'S A HUGE PIECE OF IT BUT IT'S NOT THE ONLY PIECE. I THINK INTEGRATING THIS MORE INTO PRIMARY CARE OF COURSE IS A BIG PART OF WHAT WE NEED TO DO MOVING FORWARD. OF COURSE, THERE WILL ALSO BE A NEED FOR SPECIALTY CARE AROUND THESE DISORDERS, BUT, THERE'S NO REASON WHY THESE THINGS SHOULDN'T BE INTEGRATED INTO PRIMARY CARE MORE. SAMHSA I DIDN'T MENTION IT IN MY REMARKS BUT SAMHSA HAS 2 PROGRAMS 1 CALLED PC SS, PHYSICIANS CLINICAL SUPPORT NETWORK FOR UNIVERSITIES AND SOMETHING CALLED PRAGMATIC TRIALS HEAD WHERE WE'RE TRYING TO INTEGRATE TRAINING INTO MEDICAL SCHOOLS WHICH IS INCREDIBLY IMPORTANT TOWARD THE HOPE THAT THIS CAN--THESE CONDITIONS CAN BE RECOGNIZED BY PRIMARY CARE DOCTORS AND OTHERS IN THE MEDICAL FIELD, MUCH SOONER AND AS YOU KNOW DEBPOINTED OUT ALTHOUGH SHE WAS TALKING ABOUT PRIME REGIMEN WITH YOUTH, PRIMARY PREVENTION WITH ADULTS IF YOU CAN DO THAT KIND OF--WITH DR. KOH YESTERDAY, YOU ALL KNOW DR. KOH, THE FORMER ASH. HE SAID AN OUNCE OF PREVENTION IS WORTH A TON OF HARD WORK. AND IT'S--IT'S REALLY HARD WORK BUT IT'S THE WORK THAT WE'VE NEED TO DO IN SOME SPACE. >> THANK YOU VERY MUCH. ANYTHING TO ADD TO THOSE COMMENTS FROM EITHER THE OTHER PANELISTS? >> WELL, I GUESS, MY THOUGHT, LARRY, YOU KNOW I ALWAYS LIKE AIAN LITTLE OUT FROM LEFT FIELD FROM EVERYBODY ELSE, I HAVE ALCOHOLISM IN MY FAMILY WITH SOME VERY SEVERE DISEASE, AND BUT RECOVERY IN SOME CASES WHICH IS VERY GOOD. BUT I WAS STRUCK GOING THROUGH THIS BECAUSE THEY TURN TO THE MEDICAL PERSON IN THE FAMILY TO HELP. I WAS STRUCK HOW IN RECOVERY AS--FIRST OF ALL THE STIGMA IS APPALLING AND DEADLY AND PERVASIVE AND JUST AMAZING AND SECOND OF ALL, I DON'T KNOW, I THINK THOSE HAVE TO BE--THOSE HAVE TO BE A WHOLE SOCIETAL EDUCATION BUT THE HEALTHCARE WORKERS SEEM TO BE THE WORST PEOPLE AT THIS AND WHAT I WAS MOSTLY STRUCK BY IN RECOVERY IS HOW THE PEOPLE IN RECOVERY HAVE TAKEN THIS ENTIRE AREA AND THEY MANAGE RECOVERY BECAUSE IT SEEMS LIKE THE HEALTHCARE SYSTEM AND MEDICALIZATION OF THIS HASN'T BEEN SUCCESSFUL AND THE MORE SUCCESSFUL INTERVENTIONS HAVE BEEN BY COMMUNITIES THEMSELVES, COMMUNITIES OF PEOPLE IN RECOVERY AND SO I THINK THAT NEEDS TO BE EXPLORED MORE, I'M NOT SURE. I'M NOT REALLY SURE HAVING GONE THROUGH THIS PERSONALLY SOME THAT MEDICALIZATION OF THIS IS THE RIGHT PATH FORWARD FOR RECOVERY. CERTAINLY THE MEDICAL HEALTHCARE SYSTEM HAS TERRIBLIBLE STIGMA EMBEDDED IN IT AND HAS TO SOMEHOW GET OVER THAT AND THAT IS IMPORTANT FOR COMPASSIONATE INITIAL TREATMENT AND PROBABLY PREVENTION AS WELL MPLET BUT AS FAR AS RECOVERY, I THINK, I'M SOCIAL MEDE WRA AND ALL THE DIFFERENT WAYS PEOPLE HAVE CONNECTING NOW, I JUST--I JUST WONDER IF MEDICAL IMPLEMENTATION IS NOT A PATH TO USE AND I HOPE THAT THAT IS STUDIED QUITE A BIT. >> THANK YOU SO MUCH. I DON'T THINK THAT'S OUT IN LEFT FIELD AT ALL. >> OH, OKAY. >> BUT OKAY, DEBANY FINAL COMMENT ON THAT POINT AND THEN WE ARE A COUPLE QUESTIONS IN THE CHA THE BOX THAT I WOULD LIKE TO TURN TO BUT PLEASE, DEBIF THERE ARE ANY OTHER THINGS YOU WOULD LIKE TO SAY. >> I THINK I WOULD JUST ADD FROM WHAT I HAVE SEEN IS IN CLINIC IS JUST EMPLOY EARS REALLY NEED TO ENGAGE IN THIS MORE BECAUSE MY PATIENTS TALK ABOUT THE STIGMA AND TRYING TO ASK TIME OFF, TO COME TO CLINIC FOR THEIR MOUD AND/OR THE SCREENING, URINE TESTS THAT I HAVE TO DO THEY'RE CONCERNED THEIR MOUD WILL HAVE TO SHOW UP AND THEY'LL HAVE TO EXPLAIN THEY'RE IN TREATMENT BECAUSE OF THE STIGMA. SO THE MORE WE CAN NORMALIZE IT AND SUPPORT PEOPLE IN RECOVERY AND IN TREATMENT, THAT HELPS. IT NORMALIZES IT AND I HEAR THAT OVER AND OVER FROM PATIENTS AND I THINK THE MORE WE CAN SUPPORT THEM IT'S REALLY IMPORTANT. >> GREAT. THANK YOU. ALL THOSE PERSPECTIVES ARE I THINK ARE VERY, VERY HELPFUL. THERE ARE A COUPLE OF QUESTIONS IN THE CHAT BOX, THE FIRST, I THINK PROBABLY JANET IS DIRECTED TO YOU ABOUT THE FDA INNOVATATION CHALLENGE WHICH THE WRITE INDICATE CITIZEN A VERY EXCITING PROGRAM. HOW CAN WE INCREASE VISIBILITY OF SIMILAR OPPORTUNITIES AMONG THE HEAL COMMUNITY. IS THERE SOMETHING YOU WOULD LIKE TO SPEAK TO ON THAT? >> WELL, I WOULD--I THANK THE QUESTIONER FOR THAT. I WILL GET BACK TO THE DEVICE PROGRAM AND SEE IF THEY PROBABLY NEED A LITTLE BIT MORE MONEY TO FIGURE OUT HOW TO HAVE ANOTHER ROUND OF THIS AND PERHAPS NIH COULD CONSIDER THIS, TOO, THIS KIND OF CHALLENGE. PEOPLE, I DON'T THINK HAD UNTIL FAIRLY RECENTLY THOUGHT OF MEDICAL DEVICES AND SOFTWARE AND THINGS LIKE THAT, AS PERHAPS CONTRIBUTING TO HELPING WITH THIS PROBLEM, BUT REALLY THAT'S WHERE A LOT OF INNOVATION IS GOING ON, SO I WILL FOLLOW UP WITH THAT, AND IF I GET ANY SPECIFIC INFORMATION, I CAN GET BACK TO YOU FOR THE PROGRAM. >> THANK YOU VERY MUCH. THE NEXT QUESTION PERHAPS EACH OF YOU WOULD LIKE TO COMMENT AND IT IS--SAMHSA MAY WANT TO TAKE THE LEAD ON THIS, THE QUESTION ASKS: YOU KNOW WE KNOW THAT POVERTY, EXPOSURE--SORRY INTERGENERATIONAL PROBLEMS, HOW DO WE COLLECTIVELY ADVOCATE FOR ACROSS THE BOARD ECONOMIC SOCIAL SUPPORTS IF ARE WOMEN, CHILDREN AND FAMILIES AS PART OF SUBSTANCE ABUSE PREVENTION? SO, WHO WOULD LIKE TO? >> IT'S A GREAT QUESTION. I DON'T KNOW THAT I HAVE THE ANSWERS FOR IT BUT WE CERTAINLY HAVE LOTS OF DATA TO SUPPORT AS DEBWAS TALKING ABOUT EARLIER WITH ACES AND OTHER SAMHSA PROGRAM DATA WE'RE HAPPY TO PROVIDE PEOPLE TO USE FOR ADSOPHISTICATED CASSIE BECAUSE WE THINK IT'S INCREDIBLE LOAMACYY IMPORTANT. THIS IS COMPLEX. I REMEMBER READING THE BOOK DREAM LAND AND WALKING AWAY THINKING WOW, THIS IS--THIS ISN'T JUST A PUBLIC HEALTH PROBLEM, THIS IS A COMMUNITY PROBLEM, IT'S AN ECONOMIC PROBLEM, IT'S AN INTERGENERATIONAL PROBLEM, I READ HILL BILLY EUOLOGY, WHERE I SAW THE SAME THINGS, SO YEAH, WE WOULD BE HAPPY TO HELP TO PROVIDE DATA AND RESOURCES SO THAT THIS CAN BE EXPLAINED MORE TO A POLICY MAKERS AND APPROPRIATORS SO THAT THEY SUPPORT YOU KNOW A LOT MORE FUNDING AND RESOURCES FOR BROAD BASED PREVENTION EFFORTS AND TRYING TO HELP INCREASE THE, YOU KNOW INCREASE THE KINDS OF SERVICES AND COMMUNITIES TO PREVENT THESE ISSUES FROM OCCURRING IN THE FIRST PLACE NGREAT.-- >> GREAT. THANK YOU. DEBDID YOU WANT TO WEIGH IN ON THAT TOPIC? , WE HAVE ADVERSE CHILDHOOD EXPERIENCES CLASSES OR SET OF STRATEGIES THAT VERY MUCH HIGHLIGHTS THE NEED FOR ECONOMIC SUPPORTS AND IT SHOWS A LOT OF THE EVIDENCE OF STUDIES THAT SUPPORT IT. I THINK YOU HAVE TO HAVE THOSE POLICY AND COMMUNITY LEVEL CHANGES, WE ALSO HAVE A REPORT THAT WE DID WITH ANOTHER PARTNER LOOKING AT EASTERN KENTUCKY AND IT SHOWS THAT AS RATES OF OVERDOSES ARE GOING UP ELSEWHERE, YOU KNOW KENTUCKY AND SURROUNDING AREAS AND EASTERN KENTUCKY THEY WERE ABLE TO DEE CREASE THEM AND EVEN SUSTAIN THOSE DECREASES AS WE SEE INCREASES BECAUSE THEY DID EXACTLY THAT. THEY PROVIDED SUPPORT TO COMMUNITIES, FINANCIAL AID, JOB SUPPORT, HOUSING, REALLY THE WHOLISTIC PACKAGE, THAT'S HOW YOU HAVE TO ADDRESS THIS. >> THAT'S GREAT. THANK YOU. SO WE HAVE TIME FOR 1 FINAL QUESTION AND JANET, IT IS TO YOU FROM DR. VOLKOW, HOW CAN WE ACCELERATE THE APPROVAL FOR MEDICATIONS FOR SUBSTANCE USE DISORDER NOW THAT WE OBSERVED HOW FAST TREATMENT CAN BE BROUGHT TO THE CLINIC WITH THE CURRENT PAN DEPRIVATIONIC? >> [LAUGHTER] WELL, OF COURSE, I HAVE GREAT EXPERIENCE IN HAVING GOTTEN LIKE 7 TRIALS UP AND RUNNING, YOU KNOW PRODUCTS THROUGH DURING THE PAST YEAR, I WOULD SAY THAT THE URGENCY FOR THIS EPIDEMIC IS VERY SIMILAR TO THE PANDEMIC. WHAT REALLY GREASED THE SKIDS HERE WAS MONEY, JUST TO BE TOTALLY BLUNT AND HONEST, OKAY? YOU KNOW RESOURCES WERE PROVIDED THE WAY IT WAS SMOOTH, ANY NEED FOR EXAMPLE, MATERIALS OR SUPPLIES, THOSE ISSUES WERE SOLVED. EVERYTHING--SETTING UP CLINICAL TRIALS STILL TAKES A WHILE UNDER ANY CIRCUMSTANCES BUT IT'S CLEAR IT CAN BE DONE MUCH FASTER THAN WE HAVE DONE AND I DON'T THINK THIS WILL HAPPEN FOR EVERY DISEASE ACROSS THE BOARD BUT SOME OF THESE DISEASES THAT ARE EPIDEMICS IN THEMSELVES SUCH AS SUBSTANCE USE SUCH AS ALZHEIMER'S DISEASE AND MANY OTHERS, WE REALLY SHOULD CONSIDER A SIMILAR ALL-OUT ASSAULT ON THAT DISEASE. >> THANK YOU SO MUCH AND I THINK THAT WOULD REALLY BE A WAY TO END THIS SESSION. YOU KNOW WE'RE SLIGHTLY OVER TIME BUT THANK YOU ALL VERY MUCH FOR YOUR CONTRIBUTIONS AND I WILL TURN THIS BACK TO DR. BAKER. >> ACTUALLY I WILL BE DR. BAKER. >> THANKS, JACK. >> YOU'VE CHANGED. [LAUGHTER] >> SO-- >> WAYS TO RESPOND ON A DIME HERE, THANK YOU. DR. TABAK AND THE TERRIFIC PANEL OF FEDERAL COLLEAGUES. WE ARE NOW GOING INTO BOTH A BREAK AND AN OPPORTUNITY TO VIEW POSTERS WHICH WILL YOU FIND IN THE CONFERENCE WEBPAGE AND THEN WE WILL BE RETURNING IN SMALL DISCUSSION GROUPS AT 1:00 O'CLOCK. CHECK OUT THE SESSIONS THAT WILL BE HELD CONCURRENTLY AND WILL IFING THAT WE WILL RETURN AS A LARGE GROUP SO CHECK OUT THE AGENDA AND HOPE YOU HAVE A RELAXING BREAK AND WE WILL SEE YOU BACK THIS AFTERNOON SO THANK OUR NEXT SESSION IS LED BY DR. MICHAEL OSHINSKY, NINDS, TWO OVERSEES PROGRAM IN PAIN AND MIGRAINE. >> THANK YOU, JACK. I'M THE PROGRAM DIRECTOR, ALSO CO-CHAIR FOR THE PRE-CLINICAL AND TRANSLATIONAL PAIN PORTION OF THE HEAL INITIATIVE. TODAY WE HAVE THIS SESSION, HARNESSING INNOVATION IN PAIN AND ADDICTION RESEARCH. THE REAL EMPHASIS ON THE NEXT FIVE PRESENTATIONS THAT YOU'RE GOING TO SEE IS INNOVATION IN PROVIDING NEW AVENUES AND NEW METHODS FOR TREATING PAIN AND ADDICTION THAT HAVE VERY LITTLE OR NO ADDICTION LIABILITY. THE TYPES OF APPROACHING YOU'LL SEE ARE SMALL MOLECULES THAT HIT MULTIPLE RECEPTOR SYSTEMS, AND SEVERAL DIFFERENT APPROACHES FOR TAKING ADVANTAGE OF NON-NEURONAL TARGETS FOR TREATING PAIN AND ADDICTION, REALLY LOOKING AT THE IMMUNE SYSTEM. SO, WHAT I WANT YOU TO TAKE OR EMPHASIZE WHEN YOU SEE THESE PRESENTATIONS IS HOW THE RESEARCHERS HAVE INNOVATED A NEW METHOD FOR EITHER VALIDATING THEIR TARGET OR DEVELOPING A THERAPEUTIC WITH A NEW TARGET IN ORDER TO OVERCOME, YOU KNOW, THIS VERY DIFFICULT PROBLEM WE HAVE OF TREATING PAIN AND ADDICTION, OPIOID USE DISORDER. SO THE FORMAT FOR THE SESSION IS THAT IN ADDITION TO MYSELF THERE'S ALSO A P.I. FACILITATOR, DR. DR. MARCO PRAVETONI, WHO WILL INTRODUCE EACH SPEAKER. THERE'S A SHORT TALK OF FIVE MINUTES EACH. WE WANT TO INSPIRE EVERYONE TO SUBMIT QUESTIONS AND THERE WILL BE A LIVELY DISCUSSION AMONG PANELISTS. IN ORDER TO BRIDGE THIS GAP OF PAIN AND ADDICTION RESEARCH, REALLY DISCUSS WHERE THERE ARE POSSIBILITIES FOR INNOVATION HERE. I'LL PASS IT OVER TO DR. PRAVETONI. >> THANK YOU, MICHAEL. MARCO HERE FROM UNIVERSITY OF MINNESOTA. IT'S MY PLEASURE TO INTRODUCE OUR FIRST SPEAKER, DR. SANDRA COMER, FROM COLUMBIA UNIVERSITY, PROFESSOR OF NEUROBIOLOGY, DEPARTMENT OF PSYCHIATRY AND RESEARCH SCIENTIST AT SHE WILL BE TALKING TO APPROACH TO OPIOID USE DISORDER. >> THANK YOU FOR THE INTRODUCTION. I'D LIKE TO THANK EVERYONE FOR ATTENDING THIS SESSION. SO TODAY I'M GOING TO TALK ABOUT A NEW CHEMICAL ENTITY, WE CALL IT ITI-333. I'M WORKING ON THIS COMPOUND IN COLLABORATION WITH MY COLLEAGUES AT INTRACELLULAR THERAPIES, GRETCHEN SNYDER AT THE COMPANY IS THE CONTACT P.I. ON THIS PROJECT. NEXT SLIDE. THESE ARE SOME OF OUR DISCLOSURES. ITI-333, WHICH I'LL CALL 333 THROUGHOUT THE PRESENTATION, HAS A UNIQUE PHARMACOLOGY, BINDS WITH LOW NANOMOLAR AFFINITY TO SEROTONIN, MU OPIOID RECEPTORS WITH VERY ALSO AT OTHER RECEPTORS. IT FUNCTIONS AS A PARTIAL AGONIST, PRIMARY SIGNALING THROUGH G-PROTEIN PATHWAYS, ANTAGONIST, SEROTONIN 2A RECEPTORS, IMPLICATIONS FOR EFFECTS ON MOOD AND PSYCHIATRIC DISORDERS. AND IT MAY ACT SYNERGISTICALLY AT THIS RECEPTOR WITH MU OPIOID RECEPTORS TO REDUCE PAIN AND, ANTAGONIST AT D1 RECEPTORS, IMPLICATIONS FOR TREATING SUBSTANCE USE DISORDERS. IT HAS EXCELLENT PK PRODUCTS, AND GOOD BRAIN PENETRATION. IT DOES NOT APPEAR TO PRODUCE PHYSICAL DEPENDENCE, AND IT HAS APPARENTLY NO EFFECTS ON G.I. MOTILITY OR RESPIRATORY FUNCTIONING. SO, THE COMBINED RECEPTOR PHARMACOLOGY OF 333 SUGGESTS IT MIGHT BE FOR TREATING PAIN, SUBSTANCE USE DISORDERS AND CO-OCCURRING PSYCHIATRIC DISORDERS. NEXT SLIDE. SO HERE I'M SHOWING YOU THE BINDING PROFILE OF THIS COMPOUND, SO YOU CAN SEE THAT IT'S -- IT BINDS WITH LOW NANOMOLAR AFFINITY TO THREE RECEPTORS I DESCRIBED, TESTED IN A PANEL OF MANY OTHER RECEPTORS AND HAD VERY LITTLE OR NO ACTIVITY AT THESE OTHER SITES. NEXT SLIDE. SO I'M SHOWING YOU HERE THE ANALGESIC EFFECTS OF THIS COMPOUND IN MICE, USING A TAIL FLICK ASSAY. ON THE LEFT I'M SHOWING YOU THE ANALGESIC EFFECTS AFTER SUBQ, ON THE RIGHT YOU CAN SEE AFTER ORAL ADMINISTRATION, IT PRODUCED DOSE-RELATED INCREASE BY BOTH ROUTES OF ADMINISTRATION, THE BLACK BARS ARE SHOWING EFFECTS OF MORPHINE, EEFFECTS BLOCKED BY NALOXONE. NEXT SLIDE. THERE APPEARS TO BE VERY LITTLE TOLERANCE DEVELOPMENT AFTER CHRONIC ADMINISTRATION, SO ON THE LEFT IS CHRONIC VEHICLE ADMINISTRATION, IN THE MIDDLE IS LOW DOSE OF REPEATED ADMINISTRATION OF 333. GIVEN OVER TWO WEEKS. AND THEN THE RIGHT PANEL SHOWS THE HIGH DOSE. SO, THERE IS SOME DECREASE IN EFFECTS BUT IT'S NOT VERY ROBUST. SO THE ANALGESIC EFFECTS OF THIS COMPOUND ARE SUSTAINED. NEXT SLIDE. SO, AS A PARTIAL AGONIST, PARTIAL MU OPIOID AGONIST, OF COURSE WE'RE WORRIED ABOUT ITS ABUSE LIABILITY. SO TWO STUDIES WERE CONDUCTED. ONE WAS DONE IN RATS, ANOTHER DONE IN RHESUS MONKEYS, USING THE GOLD STANDARD PROCEDURE SO THIS WAS AN INTRAVENOUS SELF-ADMINISTRATION PARADIGM USED IN BOTH RATS AND MONKEYS. IN THE LEFT PANEL, THE RED TRIANGLE SHOWS SELF-ADMINISTRATION OF HEROIN. YOU CAN SEE THE COMPOUND HAD NO REINFORCING EFFECTS IN RATS. AND IN RHESUS MONKEYS WE SAW SIMILAR OUTCOME, BLACK BARS SHOWING YOU EFFECTS OF SELF-ADMINISTRATION OF HEROIN, AND NONE OF THE DOSES OF THE COMPOUND UP TO THE SOLUBILITY LIMIT WAS SELF-ADMINISTERED. NEXT SLIDE. SO JUST TO SUMMARIZE IN TERMS OF ITS EFFICACY, AGAIN, IT HAS THIS REALLY KIND OF UNIQUE PHARMACOLOGY WITH ACTIVITY AT THESE THREE RECEPTOR SUBTYPES. IT IS AN ANTAGONIST AT SEROTONIN AND D1 RECEPTORS, PARTIAL AGONIST AT MU. THE ACTIVITY AT MU IS THROUGH THE G-PROTEIN SITE, WHICH IS IMPORTANT IN TERMS OF, YOU KNOW, ADVERSE EFFECTS THAT OPIOIDS CAN PRODUCE. IT HAS EXCELLENT PK PROFILES. IT'S POTENT AND EFFICACIOUS AS AN ANALGESIC. I DIDN'T SHOW THESE DATA BUT IT IS ALSO EFFECTIVE AT SUPPRESSING HEROIN Q INDUCED RESPONDING IN RATS AND ALLEVIATES PHYSICAL WITHDRAWAL SYMPTOMS IN ANIMALS MADE DEPENDENT ON OXYCODONE. NEXT SLIDE. AND VERY IMPORTANTLY, THERE'S NO EVIDENCE OF ABUSE LIABILITY IN THESE MODELS. THIS IS IMPORTANT BECAUSE THERE'S GOOD TRANSLATION GENERALLY BETWEEN THE PRE-CLINICAL AND CLINICAL MODELS FOR ABUSE LIABILITY FOR OPIOIDS. AND IT APPEARS TO BE PRETTY SAFE. IT DOES NOT INCREASE LOCOMOTOR ACTIVITY, DOES NOT INHIBIT G.I. MOTILITY AND ALSO DOESN'T PRODUCE RESPIRATORY DEPRESSION. NEXT SLIDE. SO WE HAVE BEGUN TESTING IN HUMANS. SO WE'RE IN THE MIDST OF THE SINGLE ASCENDING DOSE STUDY. WE ARE JUST ABOUT TO ENROLL COHORT 4, I THINK ON JUNE 4 WHEN WE WILL ADMIT THAT GROUP. THUS FAR IT'S BEEN VERY WELL TOLERATED. SO, AFTER THE STUDY WE'LL INITIATE A MAT STUDY AND ALSO PET STUDY, AND IN THE UH3 PHASE WE'LL CONDUCT SOME EARLY PHASE 2 STUDIES TO LOOK AT PRELIMINARY EFFICACY IN PEOPLE. THANK YOU. I'D LIKE TO THANK NIDA FOR SUPPORTING THIS RESEARCH. >> I'M DAVID CLARK FROM STANFORD UNIVERSITY, I'D LIKE TO SPEAK FOR A FEW MINUTES ABOUT A NOVEL TARGET THAT WE THINK MIGHT BE USEFUL IN DESIGNING NOVEL THERAPEUTIC. MY THANKS TO THE NIH AND FOR BEING INVITED TO SPEAK TO YOU FOR A FEW MINUTES ABOUT THIS PROJECT. VERY RECENTLY INITIATED WITH MY CO-INVESTIGATORS DR. ANGST AND MARCELIN-LITTLE AT UC-DAVIS. THE CONCEPT IS THE IDEA AUTOIMMUNE CONTRIBUTIONS MIGHT BE SIGNIFICANT IN CERTAIN PAINFUL DISEASES, AND THAT MIGHT SEEM A LITTLE HERETICAL AT FIRST BUT FEW DOUBT IT HAS TO DO WITH DISEASES, THERE ARE SPECIFIC DISEASE, SOME NEUROLOGICAL, GUILLAIN-BARRƒ OR ANTI-LIKE PROTEIN NEUROPATHY WHERE NEURONS ARE ATTACKED SPECIFICALLY LEADING TO PAIN AS PART OF THE DISEASE PHENOTYPE. THERE ARE RARER SYNDROMES WHERE THINGS LIKE POTASSIUM ION CHANNEL COMPLEXES CAN BE TARGETED, PAIN IS ONE OF THE FIRST SYMPTOMS DISPLAYED IN RESPONSE TO AUTOANTIBODIES IN SO-CALLED PERINEOPLASTIC SYNDROMES. FOR SEVERAL YEARS OUR GROUP WORKED WITH THE HYPOTHESIS AFTER TRAUMA AND IN THE SETTING OF FAIRLY UNCOMMON PAIN SYNDROME, COMPLEX REGIONAL PAIN SYNDROME, AUTOIMMUNE PHENOMENA MIGHT BE AT WORK IN THE MECHANISM ON THE RIGHT-HAND SIDE OF THE SCREEN DESCRIBING SOME OF THAT WORK, WE BELIEVE THERE'S NEURAL CONTROL OF THE ACTIVATION OF BOTH INNATE AND ADAPTIVE IMMUNE SYSTEMS, FOCUSING ON ADAPTIVE WE SEE PRODUCTION OF IMMUNOGLOBULIN TYPE M, RESULTING IN COMPLEMENT ACTIVATION CYTOKINE PRODUCTION AND WE BELIEVE THE EXPERIENCE OF PAIN. AS PART OF THE PROJECT WE'RE UNDERTAKING, A TARGET VALIDATION PROJECT, WE'LL BE LOOKING AT OTHER DISEASE MODELS BOTH IN HUMANS AND IN ANIMAL MODELS FOR POSSIBLE IMMUNE CONTRIBUTIONS. NEXT SLIDE PLEASE. SO SOME OF THE DATA AS FOLLOWS. THE UPPER LEFT-HAND CORNER YOU CAN SEE AFTER WE TRACK TIBIAS OF MICE, IMMOBILIZE FOR THREE WEEKS, REMOVE CASE, ALLODYNIA LASTING FOUR OR FIVE MONTHS, LIKEWISE UNWEIGHTING OF ANIMAL AS WE ASK IT TO STAND ON OPPOSED SCALES, LESS SENSITIZATION IF ANIMALS OF THE MU MT STRAIN WHICH DON'T PRODUCE MATURE CELLS, RUNNING ON EXERCISE ARE ALSO IMPAIRED AFTER MANEUVERS. WHEN WE WENT LOOKING FOR THE PUTATIVE AUTOANTIBODIES WE FOUND IgM HIGH LEVELS IN THE SKIN AND SCIATIC NERVE, SPINAL CORD TISSUE FOR DURATION OF SENSITIZATION, WE COULD MEASURE BEHAVIORALLY, SUCCESSFUL IN TRANSFERRING SERA AND PURIFIED IMMUNOGLOBULINS FROM FRACTURED WILDTYPE ANIMALS TO THE B CELL-LESS MU MT ANIMALS RECONSTITUTING PAIN PHENOTYPE, WHEN WE INJECT IgM INTO THE FRACTURED ANIMALS WE CAUSE TRANSIENT SENSITIZATION WITH DURATION OF THE SAME PERIOD OF TIME WE WOULD EXPECT FOR THE HALF-LIFE OF THAT ANTIBODY. FINALLY WE'VE DONE SOME WORK TRANSLATIONALLY WHERE IN HUMANS WITH COMPLEX REGIONAL PAIN SYNDROME IF WE TAKE THEIR SERA AND GIVE IT TO THE MICE, SO THAT'S HUMAN TO MOUSE TRANSFER OF SERUM OR PURIFIED IMMUNOGLOBULIN, THOSE WITH RELATIVELY ACUTE COMPLEX REGIONAL PAIN SYNDROME, LESS THAN A YEAR, ALMOST UNIVERSALLY CAUSE DESENSITIZATION, VERY FEW FROM A YEAR OUT CAUSE THAT. PART OF THE INNOVATION THAT WE HOPE WILL BE SUCCESSFUL IN OUR PROJECT IS TO FOCUS ON TRANSLATION. WE HAVE OF COURSE ANIMAL MODEL WE'VE WORKED WITH FOR SEVERAL YEARS BUT WE'LL BE WORKING WITH DR. ANGST ON COLLECTING BOTH BEHAVIORAL DATA AND SERUM SAMPLES FROM PATIENTS UNDERGOING KNEE REPLACEMENT SURGERY, AS A TYPE OF SURGERY THAT'S ASSOCIATED WITH CHRONIC PAIN IN ABOUT 25% OF CASES. HERE YOU SEE PILOT DATA SHOWING SOMEWHERE BETWEEN 40 AND 50% OF THOSE PATIENTS SIX WEEKS OR MORE AFTER SURGERY CONTINUE TO HAVE THESE PRO NOCICEPTIVE, I'LL CALL THEM, SERA. AND WE TRY TO DETERMINE WHETHER THERE'S CORRELATION BETWEEN HAVING PRO NOCICEPTIVE SERUM AND PERSISTENT PAIN IN THOSE PATIENTS. I DON'T KNOW THE ANSWER. LIKEWISE WE HAVE A PARTNERSHIP WITH A VETERINARY SURGEON, DR. MARCEL-LITTLE AT UC-DAVIS VETERINARY SCHOOL, COLLECTING SPECIMENS FROM DOGS UNDERGOING KNEE SURGERY. THEY HAVE A TENDENCY TO HAVE KNEE PROBLEMS, THERE'S ANS OSTEOTOMY AND TRY TO CORRELATE PRESENCE OF IMMUNE PHENOMENA WITH PERSISTENT DIFFICULTIES IN RECOVERY AFTER SURGIES. LAST SLIDE PLEASE. IN OUR PROJECT WE WANT TO VALIDATE OR INVALIDATE THE B CELL AS A TARGET FOR ANALGESIC PURPOSES, IN ADDITION TO EXPERIMENTS I'VE SHOWN TO YOU WE'LL LOOK AT SYMPATHECTOMY, ANTI-IL, REDUCING B CELL AVENUES,' EFFECTS OF SEX AND AGE TO SEE IF IN FACT THESE ARE GENERALIZABLE TO THOSE POPULATIONS AS WELL. WE'RE GOING TO DETERMINE WHETHER NOM -- PHENOMENA ARE UNIQUE TO POSTTRAUMATIC SYNDROME. LUMBAR DISC INJURY WE BELIEVE WE'LL HAVE SOME LUCK, OSTEOARTHRITIS, INTERESTING OBSERVATIONS, PERHAPS LESS SO FOR STRAIGHT INCISION. FINALLY WE HOPE THAT IT WILL BE INFORMATIVE AND TRANSLATIONALLY HELPFUL TO HAVE DATA FROM CANINE AND HUMAN SAMPLES. THANK YOU, THAT CONCLUDES MY REMARKS. >> I'M GOING TO INTRODUCE THE NEXT SPEAKER, DR. PAUL KENNY, ICAHN SCHOOL OF MEDICINE. THANK YOU. >> THANK YOU, MARCO. THANK YOU, MICHAEL, AND THE ORGANIZERS FOR THE INVITATION. I'M GOING TO SHOW A FEW SLIDES ON A PROGRAM THAT WE HAVE IN THE LAB SPONSORED BY NIDA TO DEVELOP NOVEL THERAPEUTICS, FOCUSED ON MODULATION OF GPR151. NEXT SLIDE PLEASE. SO, WHY ARE WE FOCUSED ON GPR151? WELL, THE REASON IS BECAUSE RECEPTOR IS HIGHLY ENRICHED IN REGION OF THE BRAIN CALLED, EVIDENCE HAS EMERGED SUGGESTING THAT THE MEDIA HABENULA PLAYS A CRITICAL ROLE IN REGULATING ANALGESIC PROPERTIES OF OPIOIDS, VERY LIKELY INVOLVED IN MANY ADDICTIONAL RELEVANT PROPERTIES OF OPIOIDS. ACTUALLY COMPELLING EVIDENCE SUGGESTING IF YOU MANIPULATE, YOU AFFECT THE TWO IMPORTANT RESPONSES. WE THINK IF WE CAN MANIPULATE THE HABENULA MAY BE ABLE TO GENERATE NON-OPIOID ANALGESICS AND ADDRESS WHAT WE THINK HELPS TO DRIVE AND SUSTAIN OPIOID ADDICTION, OPIOID DEPENDENCE. HOW DO WE MANIPULATE THE HABENULA? THERE'S A RECEPTOR THAT'S REALLY ENRICHED IN THE HABENULA, IT'S EXPRESSED ALMOST EXCLUSIVELY IN THE HABENULA. THE ONLY OTHER REGION THIS RECEPTOR IS KNOWN TO BE EXPRESSED IN IS THE DORSAL ROOT GANGLIA, THAT RECEPTOR IS AN ORPHAN G COUPLED RECEPTOR, GPR151, ORPHAN BECAUSE UP UNTIL NOW THE ENDOGENOUS LIGAND THAT MODULATES GPR151 ACTIVITY HAS NOT BEEN KNOWN. ON THE LEFT IS SHOWN ACTIVITY, AND IN HUMAN HABENULA, ON THE RIGHT FROM THE BRAIN ATLAS, SCREEN GRAB, LONG BROWN LINE IS BASICALLY THE MEDIAL HABENULA, AND PROJECTIONS TO THE SITE TO WHICH THE NEURONS PROJECT, WHICH IS THE IPN, AND IN THOSE NEURONS THERE'S SIGNIFICANT ENRICHMENT IN RECEPTORS CONSISTENT WITH WHAT WE THINK HABENULA IS DOING, WHICH IS PLAYING AN IMPORTANT ROLE IN REGULATING RESPONSES TO ADDICTIVE DRUGS LIKE OPIOIDS. SO NEXT SLIDE PLEASE. SO, THERE'S NOW EVIDENCE SUGGESTING THAT GPR151 PLAYS A ROLE IN REGULATING PAIN STATES, NUMBER OF PAPERS PUBLISHED SHOWN IN KNOCKOUT MICE, THAT PAIN PROCESSING IS VERY MARKEDLY QUITE PROFOUNDLY ALTERED IN THOSE ANIMALS. THERE'S ALSO NOW DATA SUGGESTING GPR151 IN THE HABENULA IS ONE OF THE MOST UPREGULATED GENES ACROSS ANY BRAIN REGION IN ANIMALS SUBJECTED TO PAIN, SAME TRUE FOR DORSAL ROOT GANGLIA, IN TERMS OF GENE EXPRESSION. WE'VE COLLECTED DATA, ROCKEFELLER UNIVERSITY IS OUR COLLABORATOR ON THIS PROJECT. WE FOUND BEHAVIORAL RESPONSES TO OPIOIDS SUCH AS MORPHINE, HEROIN, OXYCODONE, ARE REALLY MARKEDLY ALTERED IN GPR151 KNOCKOUT MICE, SO SHOWN IN THE MIDDLE IS STIMULANT RESPONSE TO OPIOIDS, IN THIS CASE MORPHINE, KNOCKOUT MICE ARE VERY RESISTANT TO THIS BEHAVIORAL RESPONSE TO THE OPIOID. ON THE RIGHT IS INTRAVENOUS SELF-ADMINISTRATION BEHAVIOR, WE MAKE OXYCODONE AVAILABLE TO ANIMALS AND WHAT WE FIND IS MARKED INCREASE IN TERMS OF SELF-ADMINISTRATION BEHAVIOR IN KNOCKOUT MICE WHICH WE INTERPRET AS DIMINISHED SENSITIVITY TO THE MOTIVATIONAL PROPERTIES OF THE DRUG, REWARDING PROPERTIES OF THE DRUG, FORCING THE KNOCKOUT TO COMPENSATE BY CONSUMING MORE OF THE DRUG THAT'S AVAILABLE. SO WE'VE GOT MUCH MORE DATA SUPPORTING A ROLE FOR GPR151 AND HABENULA IN REGULATING BEHAVIORAL RESPONSES TO OPIOIDS. NEXT SLIDE PLEASE. SO, BASED ON THESE DATA THAT WE'VE BEEN COLLECTING IN THE PUBLISHED LITERATURE SUGGESTING THAT THIS IS A REALLY INTERESTING TARGET WE SET UP, ESTABLISHED A HOST OF CELL-BASED FUNCTIONAL ASSAYS WHEREBY WE CAN TRACK THE ACTIVITY OF GPR151, AND MORE IMPORTANTLY WE CAN SCREEN GPR151 AND THESE FUNCTIONAL ASSAYS AGAINST VARIOUS SMALL MOLECULES, THIS IS SOMETHING WE'VE BEEN DOING INTERNALLY, ALSO WE'VE PARTNERED WITH NCATS WHO HAVE BEEN HELPING US TO SCREEN ALSO, AND BASED ON THOSE EFFORTS WE'VE IDENTIFIED A NUMBER OF SMALL MOLECULE REGULATORS OF GPR151, AND ALSO SERENDIPITOUSLY BELIEVE WE'VE DEORPHANNIZED RECEPTOR, WE HAVE A GOOD IDEA WHAT WE THINK ACTIVATES THE RECEPTOR ENDOGENOUSLY, AND WHAT IT'S DOING ENDOGENOUSLY. AND SO THAT'S NICE INTERESTING BIOLOGY BUT THE AIM OF THE PROGRAM IS DEVELOP NOVEL THERAPEUTIC, AND SO WITH THE SUPPORT OF NIDA, WE'RE FOCUSING MEDICINAL SERIES OVER THE NEXT 18 MONTHS, AND MAKING I THINK QUITE GOOD PROGRESS IN THAT REGARD. THAT'S IT. THANK YOU. >> THE NEXT SPEAKER DR. CAO, ASSOCIATE PROFESSOR, DEPARTMENT OF ANESTHESIOLOGY, WASHINGTON UNIVERSITY IN ST. LOUIS. DR. CAO, IF YOU WANT TO START YOUR PRESENTATION. >> I SEE DR. CAO IS UNMUTEDDED BUT I CANNOT HEAR HER. >> YOU CAN TRY AT THE BOTTOM LEFT, THERE SHOULD BE A MUTE BUTTON, COLLECT THE UP ARROW TO SELECT A DIFFERENT MICROPHONE. I WOULD TRY THAT FIRST. WE STILL CANNOT HEAR YOU UNFORTUNATELY. >> DID THAT WORK? >> YES. THERE WE GO. WE CAN HEAR YOU. >> OKAY. SORRY FOR WASTING ALL THESE TIMES. NEXT SLIDE PLEASE. SO WE'RE TRYING TO REVISE NEURONAL SENSITIZATION UNDERLYING SEVERAL CHRONIC HEADACHE DISORDERS, INCLUDING CHRONIC MIGRAINE POSTTRAUMATIC HEADACHE AND MEDICATION OVERUSE HEADACHE BY MODULATING INTERACTIONS RATHER THAN RAPIDLY, YOU KNOW, TARGETING NEURONS THEMSELVES. SO, PREVIOUS STUDIES SHOW THAT NEURONS IN THE TRIGEMINAL VASCULAR SYSTEMS CAN BE SENSITIZED BY MANY TYPES OF IMMUNE CELLS, AND BY THE VARIOUS INFLAMMATORY MEDIATORS SECRETED BY THESE CELLS. WE REASON THAT TARGETING THE INDIVIDUAL CELLS OR INDIVIDUAL MOLECULES LIKELY WILL, YOU KNOW, REVERSE SENSITIZATION, ONLY SMALL SUBSET OF PATIENTS. SO IN ORDER TO FIND THE TREATMENT FOR BROADER SPECTRUM OF PATIENTS, WE TURN TO T REGS, A SPECIAL SUBPOPULATION OF CD4 POSITIVE T CELLS THAT EXPRESS TRANSCRIPTION FACTOR FOX FOXP3 ON A THE PLASMA MEMBRANE, KNOWN TO EMPLOY MULTIPLE MECHANISMS TO SUPPRESSION FUNCTION OF IMMUNE CELLS TO MAINTAIN HOMEOSTASIS. WE WANTED TO KNOW WHETHER ENHANCING ENHANCING TREG CELL FUNCTIONING CANS USED TO TREAT CHRONIC HEADACHE DISORDERS. TURNS OUT LOW DOSE INTERLEUKIN-2 TREATMENT HAS BEEN USED IN CLINICAL TRIALS TO PREFERENTIALLY EXPAND AND ACTIVATE TREG CELLS IN PATIENTS WITH AUTOIMMUNE CONDITIONS, SHOWING EXCELLENT SAFETY PROFILE WITH INDICATIONS OF EFFICACY AGAINST MULTIPLE AUTOIMMUNE DISEASE. WE ASKED WHETHER LOW DOSE INTERLEUKIN-2 CAN BE REPURPOSED. WE TREATED MIKE WITH 1 MICROGRAM EVERY DAY, DOUBLED THE NUMBER OF TREG CELLS IN THE PERIPHERAL BLOOD SIMILAR TO HUMAN TRIALS ON THE LEFT. NEXT SLIDE PLEASE. AND HERE WE MODELED CHRONIC MIGRAINE STATE IN MICE WITH NITROGLYCERIN, REPEATED ALSO IN INDUCES FACIAL SKIN HYPERSENSITIVITY IN HUMANS AND MICE. THE FIGURE ON THE LEFT AS YOU CAN SEE LOW DOSE INTERLEUKIN-2 TREATMENT CAN REVERSE NITROGLYCERIN-INDUCED BEHAVIORAL SENSITIZATION. ON THE RIGHT WE SHOW REPEATED LOW DOSE INTERLEUKIN-2 DOES NOT INDUCE DEVELOPMENT OF TOLERANCE. NEXT SLIDE PLEASE. AND SIMILARLY ON THE LEFT LOW DOSE INTERLEUKIN-2 ACCELERATES RESOLUTION OF BEHAVIORS RELATED TO POSTTRAUMATIC HEADACHE AFTER MILD TRAUMATIC BRAIN INJURY, AND ON THE RIGHT LOW DOSE INTERLEUKIN-2 REVERSES BEHAVIORAL SENSITIZATIONS RELATED TO MEDICATION OVERUSE HEADACHE, IN THIS CASE REPEATED INJECTION OF SUM TRIPTAN. WE CONFIRMED EFFECT OF LOW DOSE INTERLEUKIN-2 IS INDEED THROUGH THE ENDOGENOUS TREG CELLS, CAN BE ABOLISHED BY DEPLETION. LOW DOSE INTERLEUKIN-2 INCREASES NUMBER OF TREG CELLS BUT DID NOT SEE TREG CELL INCREASE IN THE BRAIN, SUGGESTING LOW DOSE INTERLEUKIN-2 SITE OF ACTION IS AT PERIPHERAL TISSUES. NEXT SLIDE PLEASE. SO LASTLY, IN THE MOUSE MODEL OF CHRONIC MIGRAINE AND POST TRAUMA HEADACHE NUMBER OF TRIGEMINAL GANGLIA NEURONS THAT RESPOND IS INCREASED SHOWN BY THE RED BAR AND LOW DOSE INTERLEUKIN-2 MECHANISM OF ACTION IS THROUGH REVERSING PERIPHERAL SENSITIZATION. NEXT SLIDE PLEASE. SO IN SUMMARY WE HAVE IDENTIFIED TREG AS A CELLULAR TARGET AND LOW DOSE INTERLEUKIN-2 AS POTENTIAL THERAPY FOR SEVERAL CHRONIC HEADACHE DISORDERS. IN ENHANCING TREG CELL FUNCTION HAS BEEN SHOWN TO ALLEVIATE NEUROPATHIC PAIN-RELATED BEHAVIORS IN MOUSE MODELS, SO ALL THESE SUGGEST THAT TARGETING NEURO-IMMUNE INTERACTION WOULD ALLOW US TO IDENTIFY NEW THERAPIES FOR CHRONIC PAIN AND IN FUTURE STUDIES WE'D LIKE TO FOCUS ON UNDERSTANDING THE MECHANISMS UNDERLYING THE THERAPEUTIC EFFECTS OF LOW DOSE INTERLEUKIN-2 AND TREGS, ALSO INTERESTED IN TRIUNE MODIFIED OF INTERLEUKIN-2 WITH LONGER HALF-LIFE AND BIOLOGICS WITH HIGHER SELECTIVITY TO TREGS, AND LASTLY ENGINEERING TREG CELLS TO MAKE THEM SAFE AND EFFECTS FOR CHRONIC PAIN THERAPY. THANK YOU VERY MUCH FOR YOUR ATTENTION. >> THANK YOU. I'M GOING TO TALK ABOUT OUR EFFORTS IN DEVELOPING VACCINES, MONOCLONAL ANTIBODIES TO REDUCE OPIOID USE DISORDERS AND OVERDOSE. SO THROUGH ACTIVE AND PASSIVE IMMUNIZATION, VACCINES AND MONOCLONAL ANTIBODIES PROVIDE THE PATIENT WITH ANTIBODIES THAT WILL SELECTIVELY BIND TARGETED OPIOID AND PREVENT ITS CROSSING IN THE BLOOD-BRAIN BARRIER, REDUCING DRUG EFFECTS SUCH AS FOR INSTANCE MANUAL MODELS WE HAVE SHOWN REDUCTION OF ANTI-NOCICEPTION, LETHALITY. WITH MONOCLONAL ANTIBODIES WE PROVIDE LONG LASTING SAFE AND SELECTIVE THERAPEUTIC AND PROPHYLACTIC INTERVENTION FOR BOTH PATIENTS, WITH OPIOID USE DISORDER, OR SUBSTANCE USE DISORDER, THEY MAY ENCOUNTER COMPOUNDS LIKE FENTANYL, FOR INSTANCE, OR PROFESSIONALS THAT RISK WITH DELIBERATE EXPOSURE SPECIFICALLY IN CONCERT, CAR FENTANYL USE, COMBINED WITH NALOXONE, BUPRENORPHINE, AS WELL MONOCLONAL ANTIBODIES COULD BE POTENTIALLY CO-ADMINISTERED IN OVERDOSE RESCUE SITUATIONS IN COMBINATION WITH NALOXONE AND OTHER AGENTS. IN ORDER TO DEVELOP VACCINES THIS IS AN OVERVIEW OF OUR BLUEPRINT, OUR PLATFORM, SO EACH COMPONENT IS VERY IMPORTANT FOR INDUCING EFFECTIVE SELECTIVE AND LONG LASTING ANTIBODY RESPONSES AGAINST THE TARGET DRUG. FOR INSTANCE, HERE WE HAVE THE DRUG MODIFIED WITH LINKER TO LARGER IMMUNOGENIC CARRIERS TO ALLOW SMALL MOLECULE TO BE RECOGNIZED BY THE IMMUNE SYSTEM AND PACKAGED IN DIFFERENT WAYS. FOR INSTANCE WE'RE -- GO BACK TO THE PREVIOUS SLIDE. YES, THANK YOU. SORRY. SO FOR INSTANCE SOME OF OUR ILL-FUNDED PROJECTS ARE EVALUATING CARRIERS SUCH AS PROTEINS, OTHER NANOPARTICLES, IMMUNE MODULATORS SUCH AS TOLL LIKE RECEPTOR AGONIST OR CYTOKINE MODULATORS TO IMPROVE VACCINE RESPONSES AGAINST A TARGET AND COULD PACKAGE TO IMPROVE ITS EFFECTS. NEXT PLEASE. HERE JUST EXAMPLE, VACCINES USED TO REDUCE FENTANYL INDUCED PHARMACOLOGICAL AND BEHAVIORAL EFFECT COMPARED TO CONTROL SHOWN OVER A RANGE OF MODALITIES OF EXPOSURE TO FENTANYL, VACCINES CAN BE USED TO TREAT OPIOID USE DISORDER AS SHOWN IN THE BOTTOM LEFT PANEL WHERE WE HAVE RAT SELF-ADMINISTRATION AND START IMMUNIZING THEM WITH FORMULATION, AND OVER TIME SHOWN VACCINATION REDUCED THE EXTENT OF INFUSIONS AND ANIMALS DO NOT COMPENSATE OR NOT TRYING TO OVERCOME EFFECTS OF THE VACCINE. ALSO VACCINES CAN PROTECT AGAINST EXPOSURE TO UNKNOWN MIXTURES, FOR EXAMPLE RATS ARE PROTECTED AGAINST A MIXTURE OF FENTANYL AND CARFENTANIL, AND DO NOT INTERFERE WITH RESCUE FROM THE LIFE-SAVING MITIGATION NALOXONE. WE'RE FINALLY STARTING TO SEE MERGING INTO THE CLINICAL SPACE, OUR MOST ADVANCED PROJECT THANKS TO "HEAL," A VACCINE, AN OXYCODONE-BASED UPTIN, EQUIPPED WITH A LINKER CONJUGATED TO SUBUNIT IN CARRIER PROTEIN, PARTICULAR VACCINE TARGETS OXYCODONE, HYDROCODONE, DOESN'T INTERFERE WITH METHADONE, BUPRENORPHINE, NOR ENDOGENOUS OPIOIDS, WE HAVE COMPLETE CAMPAIGNS, OBTAINED IND LAST APRIL AND ENROLLED FIRST PATIENTS LAST FALL. WE'RE EVALUATING THIS PARTICULAR PRODUCT IN A PHASE 1, 1B CLINICAL TRIAL OF THIS VACCINE, THE P.I. IS DR. SANDRA COMER. YOU CAN ASK HER QUESTIONS, SHE'S PART OF THE PANEL, AND MYSELF. AND WE'RE LOOKING AT SAFETY AND IMPROVEMENT EFFICACY AGAINST TARGET DRUG. BETWEEN GROUPS, PLACEBO-CONTROLLED DESIGN INVOLVING TWO DOSES TESTED IN SUBJECTS, WITH OPIOID DISORDER. YOU CAN SEE IN THE CARTOON AFTER SCREENING PHASE WE'RE INVOLVING SEQUENTIAL INPATIENT AND OUTPATIENT WHERE WE VACCINATE SUBJECTS OR CHALLENGE THEM AND WE EVALUATE THEM FOR A VARIETY OF PROFILES. WE'RE MOVING INTO THE CLINICAL SPACE WITH OTHER CANDIDATE VACCINES, FOR INSTANCE A HEROIN VACCINE AND COLLEAGUES AT UNIVERSITY OF MONTANA MOVING FORWARD WITH FENTANYL CONJUGATE VACCINE CONTAINING PROTEINS, DIFFERENT FORMULATION INCLUDES NOVEL AGONISTS, THE GOAL TO COME UP WITH MULTIVALENT FORMULATION THAT CAN TARGET. IN THE YEARS WE LOOK AT THE IMMUNOLOGICAL MECHANISM UNDERLYING VACCINE EFFICACY SO THAT COULD IDENTIFY POTENTIAL BIOMARKERS THAT CAN INFORM AND SUPPORT VACCINE DEVELOPMENT AND TRANSLATION. WE LOOK AT THE ENTIRE CONTINUUM FROM BEFORE TO AFTER VACCINATION, INNATE AND ADAPTIVE PROCESSES, IMMUNE SYSTEM THAT WILL THEN CORRELATE TO ANTI-DRUG ANTIBODIES AND VACCINE EFFICACY. SO THE IDEA HERE IS THAT IF WE IDENTIFY BIOMARKER WE CAN ALSO IDENTIFY AND SELECT THOSE PATIENTS THAT WILL MOST LIKELY SHOW EFFICACY. HERE WE'RE SHOWING IN MICE HOW EARLY ANTIBODY RESPONSES IN CELLS PRIOR TO VACCINATION CAN PREDICT INDIVIDUAL EFFICACY AGAINST OXYCONTIN. FINALLY WE GET TO PLAY WITH THE REAL POPULATION, SO GOING TO THE NEXT SLIDE PLEASE, CREATE A A PLATFORM, IT TAKES A VILLAGE, AND SO ESSENTIALLY WITH PARTNERSHIP WITH A LOT OF KEY PLAYERS HERE WE DEVELOPED THESE PLATFORMS THAT CAN SUPPORT THE CLINICAL TRIAL AND CAN HELP OTHER IMMUNOTHERAPEUTICS DEVELOPED BY OUR GROUP AND OTHERS, SO WE'RE LOOKING AT A HOST OF ASSAYS FOR IMMUNOPROFILING OF ANTIBODY B CELLS, CYTOKINE ANALYSIS, STRUCTURAL BIOLOGY COUPLED WITH SEQUENCING, FOR EXAMPLE B CELL RECEPTOR. BOTTOM LEFT SHOWING HOW IN INDIVIDUALS WITH OPIOID USE DISORDER, THE FREQUENCY OF OPIOID SPECIFIC B CELLS, CONFIRMING THE DATA WITH SEQUENCING OF B CELL RECEPTOR AS WELL AS STRUCTURAL BIOLOGY THAT FIGURE RIGHT THERE IS ONE OF THE ANTIBODY BINDING REGIONS IN A CRYSTAL WITH OXYCONTIN. TO GAIN FUNCTION, WE'RE LOOKING AT CYTOKINE PANEL, IDENTIFY FUNCTIONAL CLUSTERS OF CYTOKINES IN KEY ROLES IN INNATE OR ADAPTIVE IMMUNITY ASSOCIATED WITH DRUG USE. AND THIS WILL BE SUPPORTIVE, THE ACTUAL STUDY OF PLACEBO VERSUS ACTIVE VACCINE, AND HOPEFULLY WILL IDENTIFY BIOMARKERS PREDICTIVE OF VACCINE EFFICACY. NEXT SLIDE PLEASE. FINALLY WE'RE INTERESTED IN DEVELOPMENT OF MONOCLONAL ANTIBODIES TO COUNTERACT DIFFERENT ASPECTS OF OVERDOSE, CREATING A PLATFORM THAT ENABLE US TO IDENTIFY, AND THEN THIS PLATFORM ENABLES TWO PATHS, ONE CLASSICAL FUSION FOR MONOCLONAL ANTIBODIES SCREENING OR SORTING, SEQUENCING AND CLONING THE ANTIBODY REGIONS, ENABLE SCALING UP FOR TESTING, AND THIS PARTICULAR APPROACH MORE IMMUNOLOGY BASED IS PAIRED UP WITH I GUESS MONOCLONAL ANTIBODIES ENGINEERING SHOWN IN THE CARTOON IN LIKE A HEROIN ANTIBODY. EFFICACY, DEMONSTRATED MONOCLONAL ANTIBODIES CAN PREVENT IN FENTANYL, OXYCONTIN, HEROIN, IN PRE-EXPOSURE SCENARIOS, HERE UNPOLISHED DATA, WE'RE SHOWING MONOCLONAL ANTIBODIES CAN REVERSE FENTANYL INDUCED NOCICEPTION IN RATS EXPOSED TO A VARIETY OF FENTANYL DOSES. THANK YOU. THE LAST SLIDE PLEASE, AS YOU CAN IMAGINE, THIS TAKES A LOT OF COLLABORATORS, I'M THANKFUL TO ALL OUR COLLABORATORS AS WELL AS THE HEAL INITIATIVE THAT ENABLED ALL THESE STUDIES. THANK YOU VERY MUCH. >> THANK YOU TO ALL THE SPEAKERS FOR REALLY EXCELLENT TALKS. THERE'S A LOT OF POINTS HERE WE CAN BRING UP FOR DISCUSSION. THERE'S SOME LISTED ON THE SLIDE. I WANT TO START WITH THE DISCUSSION OF SOMETHING THAT DR. CLARK MENTIONED. YOU MENTIONED A COMPANION ANIMAL STUDY FOR VALIDATING YOUR TARGET OR VALIDATING IN A CLINICAL POPULATION. I WAS WONDERING IF ANY OF THE OTHER SPEAKERS -- PLEASE SPEAK A LITTLE BIT ABOUT THAT A LITTLE MORE AND THEN IF THE OTHER PANELISTS COULD TALK ABOUT WHETHER OR NOT THE USE OF COMPANION ANIMALS COULD DE-RISK THEIR TARGETS OR DE-RISK METHOD FOR TREATING PAIN AND HELP US GET INTO PATIENTS FASTER. >> SO, THE INCORPORATION OF THE COMPANION ANIMALS HAS BEEN ONE OF THE -- REALLY THE MOST, TO ME, INTERESTING PARTS OF THIS WHOLE THING. I HOPE IT TURNS OUT TO BE HELPFUL IN AN INNOVATIVE WAY. BUT, YOU KNOW, I HAVE HAD NOTHING BUT POSITIVE INTERACTIONS WITH THE VETERINARY COMMUNITY PARTNERING ON THESE PAIN QUESTIONS. IT IS A BIG CONCERN TO VETERINARIANS AND OTHER OWNERS, MANY ARE COMPANION ANIMAL OWNERS, THERE ARE MANY PAINFUL CONDITIONS, MANY ORTHOPEDIC OR SURGERY RELATED OR SO ON. I FOUND THE LEVEL OF MEDICAL AND BIOLOGICAL EXPERTISE TO BE VERY HIGH. THE INTEREST AMONGST THE COMMUNITY IN PURSUING IT VERY HIGH, SOME METHODOLOGIES TO BE MORE ADVANCED THAN I HAD PERHAPS THOUGHT, SO I LOOK FORWARD ESPECIALLY WITH OWNER-PROVIDED OBSERVATIONS OF ANIMAL BEHAVIOR. I THINK WE'RE IN VERY GOOD POSITION TO LEARN SOMETHING FROM THE ANIMALS AND THEY HAVE COME FORWARD IN SAYING THAT EVEN COMPANION ANIMAL OWNERS WOULD BE WILLING TO INVOLVE THEIR ANIMALS IN CLINICAL TRIALS OF THE THIS OF COURSE IS DISTINCT FROM DOGS USED AS LABORATORY ANIMALS. THESE ARE YOUR HOME PET. AND I THINK IT WILL BE VERY FERTILE GROUND IN THE FUTURE. >> CLINICAL POPULATIONS THAT'S NOT HUMAN, IT'S A POPULATION IN THE WILD, I THINK THERE'S A PLACE FOR THAT. DR. COMER, DO YOU THINK THERE'S A PLACE FOR THAT IN THE DEVELOPMENT OF YOUR COMPOUND ALSO FOR REDISCKING? I KNOW YOU'RE IN IN A LATER STAGE, DO YOU THINK THAT COULD BE HELPFUL FOR DE-RISKING? >> POSSIBLY. WE HAVEN'T REALLY DISCUSSED IT. SO, YOU KNOW, I'LL TAKE IT BACK TO THE TEAM AND WE'LL TALK ABOUT IT, BUT IT'S AN INTERESTING IDEA. >> SURE, SURE. ANY OF THE OTHER SPEAKERS IN THEIR PROGRAM? >> WELL, YES. I MEAN, I DON'T KNOW IF IT WOULD CLASSIFY FOR MY COMPANION ANIMALS BUT IN OUR PROGRAM ONE OF THE THINGS WE'VE BEEN STUDYING PARTICULARLY IN THE SPACE OF THE TOLL-LIKE RECEPTOR, LOOKING AT MINI PIGS AS A MODEL TO TEST FENTANYL INDUCED, AND WE STARTED WORKING WITH VETERINARIANS SPECIFICALLY THERE'S ONE OF OUR COLLEAGUE THAT ESSENTIALLY IS VETERINARIAN BUT PHARMACOKINETIC SPECIALIST, HIS ABILITY TO PUT TOGETHER LIKE THIS MODEL, PIGS WITH FENTANYL EXPOSURE, WAS AMAZING. THE OTHER THING I WOULD MENTION PROBABLY NOT AS RELATED TO "HEAL" BUT IN GENERAL DISCUSSIONS ESPECIALLY IN THE FENTANYL/CARFENTANIL EXPERIENCE USING WORK DOGS LIKES POLICE DOGS, AIRPORT, TO SEE IF THAT WOULD BE A WAY TO FIRST GET STRAIGHT TO THE FDA BUT LIKE USDA AND MAYBE THAT HELPS MOVING FORWARD. >> VERY INTERESTING. ANYONE ELSE? YOUR PROGRAM? EITHER LARGE ANIMAL STUDIES OR COMPANION ANIMAL STUDIES? DO YOU SEE THAT AS A PATHWAY FOR GETTING INTO HUMANS FASTER? >> STANDARD ANIMAL PROCEDURES USED IN ADDICTION FIELD, ONE THING WE SPENT TIME THINKING ABOUT FROM A RELATED PROGRAM WE HAVE A COLLABORATION WITH ASTRAZENECA WHICH BEHAVIORS, ENDPOINTS, TRANSLATE MOST ROBUSTLY, HOW DO YOU USE AN ANIMAL TO ACCURATELY PREDICT HUMAN DOSES, WHICH IS ALSO A REAL KEY ISSUE. IT'S BEEN EDUCATIONAL GOING BACK AND FORTH WITH THE PK/PD PEOPLE AT ASTRAZENECA USING ANIMALS IN A WAY NEW FOR ME, BEING AN ADDICTION BIOLOGIST TO LOOK AT DATA DIFFERENTLY. THE ISSUE WE HAVE OF COURSE IS SO FEW MOLECULES TRANSLATE INTO HUMANS IT'S HARD TO USE HUMAN DATASET TO REFINE ANIMAL PROCEDURE BUT HOPEFULLY AS THESE PROGRAMS MATURE INTO HUMAN CLINICAL TESTING THAT WILL HELP US REFINE ANIMAL PROCEDURES TO DEVELOP NEW MOLECULES. >> EXCELLENT. I'M HEARING COLLABORATIONS WITH VETERINARIANS OR THOSE WITH EXPERTISE IN LARGE ANIMALS WILL HELP. SOMEBODY ELSE. >> YEAH, THIS IS SANDY. I WANT TO -- JUST A WORD OF CAUTION. I THINK IT'S ALWAYS GOOD TO EXPLORE DIFFERENT TYPES OF ASSAYS AND SPECIES, TO ENRICH THE KNOWLEDGE THAT WE GAIN FROM THESE SUBSTANCES, BUT I ALSO WANT TO CAUTION ABOUT EVEN WITH THE EXISTING SPECIES WE HAVE, WE ALWAYS WORRY ABOUT THE TRANSLATABILITY AND SO THAT MIGHT INCREASE THE CONFUSION BECAUSE THERE'S -- FOR OPIOIDS IT'S USUALLY PRETTY GOOD, YOU KNOW, TRANSLATION FROM RATS TO MONKEYS TO PEOPLE, FOR EXAMPLE. BUT FOR OTHER DRUG CLASSES IT'S NOT THE CASE. SO WE HAVE TO BE REALLY CAREFULLY THINK. >> GOOD POINT. THANK YOU SO MUCH. OKAY. SO, THE NEXT DIRECTION I WANT TO GET THE DISCUSSION TO GO IN WAS TO REALLY TALK ABOUT, YOU KNOW, VALIDATING TARGETS AND HOW WE CHOOSE TARGETS FOR EITHER TREATING OUD OR IN PAIN, AND, PAUL, YOU CHOSE AN ORPHANED GPCR, GPR, BECAUSE OF ITS -- IT LOOKED LIKE YOU WERE MAKING A POINT FOR ITS LOCATION IN THE DRG, HABENULA, IMPORTANT FOR BOTH PAIN AND OUD. IF YOU COULD COMMENT A BIT ABOUT THAT TARGET SELECTION AND HOW YOU WENT THROUGH THE VALIDATION PROCESS. >> YEAH, I THINK THAT'S CRITICAL. I MEAN, FROM MY PERSPECTIVE THE HUMAN GENETICS IS ALWAYS A GREAT STARTING POINT. IF YOU'VE GOT CLEAR ALLELES IN A GENE THAT'S DRUGGABLE, THAT'S ASSOCIATED WITH A PARTICULAR DISORDER AND DISEASE, THAT'S ALWAYS A GREAT STARTING POINT. THE GENETICS, HUMAN GENETICS AROUND OPIOID USE DISORDER, AROUND PAIN, PAIN RESPONSES, NOT AS STRONG. IT'S CURRENTLY GOING TO, IN MY VIEW, BE MORE CHALLENGING TO IDENTIFY WELL VALIDATED TARGETS BY HUMAN GENETICSES ALTHOUGH THINGS ARE IMPROVING. THE OTHER APPROACH I LIKE TO CONSIDER, CIRCUIT THERAPEUTICS APPROACH, IF WE HAVE AN IDEA, REASONABLY CONFIDENT OF THAT PARTICULAR GROUP OF CELLS IN THE BRAIN ARE INVOLVED IN A DISORDER, IT WOULD BE NICE TO TARGET THOSE CELLS. EITHER THROUGH MECHANISMS LIKE DEEP BRAIN SIMULATION OR LIKE THE APPROACH WE'RE TAKING, THERE'S A RECEPTOR THAT'S SELECTIVELY EXCLUSIVELY ALMOST EXPRESSED IN THE CELLS THAT WE THINK ARE IMPORTANT, AND IF WE CAN TARGET THAT RECEPTOR WE HAVE THIS VERY KIND OF PRECISION TYPE APPROACH TO CIRCUIT THERAPEUTICS. WE'LL SEE IF THAT WORKS, BUT THERE'S A NUMBER OF COMPANIES INTERESTED IN DEVELOPING COMPOUNDS FOR NEUROPSYCHIATRIC ILLNESS IN THIS MANNER BY UNDERSTANDING CIRCUITRY BETTER AND LEVERAGING THAT INFORMATION TO IDENTIFY HOPEFULLY TARGETS THAT YOU CAN GO AFTER IN THOSE CIRCUITS AND MANIPULATE THEM IN INTERESTING WAYS. >> EXCELLENT. DOES ANYBODY ELSE WANT TO ADD TO THE DISCUSSION OF VALIDATION? AND TARGET SELECTION? THE TARGETS THAT YOU ARE USING IN YOUR WORK, YOU KNOW, HOW MUCH EVIDENCE DID YOU NEED BEFORE YOU THOUGHT IT WAS APPROPRIATE TO START DEVELOPING A THERAPEUTIC? >> FROM MY PERSPECTIVE, AGAIN. >> SURE. >> ULTIMATELY WHAT I'M SURE MANY OF THESE PROGRAMS, YOU'VE GOT TO BE ABLE TO PARTNER WITH PHARMA TO MOVE THESE INTO HUMAN. THAT, AGAIN, THE RELATIONSHIP WE'VE HAD WITH PHARMA HAS BEEN VERY EYE OPENING BECAUSE YOU GET THEIR PERSPECTIVE IN TERMS OF TYPE OF EVIDENCE THEY WILL REQUIRE BEFORE THEY -- THEY NEED TO SEE BEFORE THEY INVEST AND CONSIDER THESE LARGER SCALE HUMAN CLINICAL TRIALS WHICH ARE SO EXTENSIVE. AND SO, YEAH, THEY HAVE A WHOLE BATTERY OF EVIDENCE THAT THEY WANT TO SEE, AND SO THAT'S SOMETHING THAT WE WORK ON IN PARALLEL WITH THE, FOR EXAMPLE, CHEMISTRY EFFORTS, HUMAN GENETICS, POSTMORTEM SEQUENCE DATA, STRATIFYING PATIENT POPULATIONS TO SAY IT'S THIS GROUP LIKELY TO BENEFIT. AND SO I THINK THAT'S REALLY KEY TO KEEP THAT TYPE OF PROCESS IN MIND AS YOU'RE DEVELOPING THESE PROGRAMS BECAUSE ULTIMATELY THERE ARE QUESTIONS WE'LL BE ASKED BY PHARMA AND THOSE WE NEED TO PARER IN WITH -- PARTNER WITH TO MOVE THIS INTO THE CLINIC. >> OUR PARTICULAR PROJECT IS A LITTLE UNUSUAL. I THINK PAUL'S APPROACH IS REALLY GOING TO BE THE MORE COMMON AND BETTER MODEL. WE CHOSE A B CELL. THERE'S NOTHING SECRET ABOUT B CELLS, THERE ARE LOTS OF TOOLS TO ATTACK THE IMMUNE SYSTEM, RHEUMATOLOGY COLLEAGUES HAVE MADE GREAT PROGRESS ON THAT OVER THE LAST SEVERAL DECADES. SO IN MANY SENSES, WHAT WE'RE UNDERTAKING IN MY SHOP IS MUCH MORE STRAIGHTFORWARD, IN THAT SENSE. AND I ACTUALLY FIND THE LAYOUT OF THE EXPERIMENTS WAS RELATIVELY STRAIGHTFORWARD. WE HAD A DIFFERENT PROBLEM THOUGH THAT CAME UP, MIGHT COME UP FOR PAUL. I HOPE IT DOESN'T, CONSEQUENCES OF DRUGGING YOUR TARGET. IT'S ONE THING TO BE ABLE TO MANIPULATE THE ACTIVITY MOLECULE OR CELL, ANOTHER FOR THAT TO BE A THING WHICH ON BALANCE IS GOOD FOR BALANCE BUT DOESN'T JEOPARDIZE ANOTHER ASPECT OF HEALTH. YOU WIPE OUT SOMEBODY'S IMMUNE SYSTEM, THERE ARE CONSEQUENCES, SO I THINK WE'RE GOING TO BE CHALLENGED WITH THIS BIG QUESTION OF SELECTIVITY AND DEGREE, VERY QUICKLY. WE'VE NOT ESCAPED THE VERY IMPORTANT ASPECT OF VALIDATION, WHICH IS THE SAFETY OF TARGETING THAT PARTICULAR STRUCTURE. >> GREAT POINT, DAVE. >> I AGREE WITH WHAT YOU SAID, DAVE. I WAS GOING TO MENTION THAT AS WELL. I HAVE A KIND OF UNIQUE BACKGROUND IN PRE-CLINICAL RESEARCH AND THEN I MOVED INTO THE CLINICAL ARENA, AND, YOU KNOW, I THINK THERE'S BEEN NOT ENOUGH ATTENTION PAID TO SAFETY-RELATED ISSUES IN A LOT OF MODELS WE USE FOR CHARACTERIZING SOME OF THESE SUBSTANCES, AND FOR CERTAIN, YOU KNOW, CLASSES OF MEDICATIONS THEY HAVE DONE A LOT BETTER JOB OF PAYING ATTENTION TO THE SAFETY-RELATED ISSUES, BUT IN THIS SPACE FOR SUBSTANCE USE DISORDERS WE NEED TO BE A LITTLE BIT MORE OR A LOT MORE -- PAY A LOT MORE ATTENTION TO THAT IN THE PRE-CLINICAL MODELS. I MEAN IF SOMEONE ASKED A QUESTION ACTUALLY IN THE Q&A, YOU KNOW, ABOUT SEDATING EFFECTS, THAT'S NOT ROUTINELY ASSESSED IN A LOT OF THE ANIMAL MODELS, FOR EXAMPLE. AND, YOU KNOW, THERE'S SO MANY, YOU KNOW, EXAMPLES OF MEDICATIONS THAT LOOK REALLY GOOD, YOU KNOW, IN THE PRE-CLINICAL STUDIES AND THEN THEY JUST DON'T MAKE IT IN CLINICAL TESTING. EITHER FOR, YOU KNOW, ADVERSE EFFECTS LIKE SEDATION OR FOR JUST TOLERABILITY, YOU KNOW, THE PEOPLE JUST WON'T TAKE THE MEDICATION. SO WE REALLY NEED TO PAY ATTENTION. >> WE TRIED TO ADDRESS THAT FROM NIH PERSPECTIVE IN SOME OPPORTUNITIES FOR THERAPEUTICS DEVELOPMENT TO MAKE SURE TESTS ARE INCLUDED IN THE FORM OF CONTRACTS THAT WE GIVE ACCESS TO THE RESEARCHERS WHO CAN DO THAT FOR YOU OR IN PSPP PROGRAM, THE PROFILING. DR. CAOU, A FEW QUESTIONS WERE POSED RELATED TO SEX DIFFERENCES IN THE EFFECTS THAT YOU WERE SHOWING. COULD YOU ADDRESS ANY SEX DIFFERENCES THAT YOU'VE SEEN OR WHAT KIND OF SEX DIFFERENCES YOU'VE LOOKED AT? >> RIGHT. CHRONIC HEADACHE DISORDERS ARE KNOWN TO AFFECT WOMEN, A LOT MORE WOMEN THAN MEN, THREE TIMES MORE WOMEN. SO IN OUR TEST WE TESTED BOTH MALE AND FEMALE INBRED AND OUTBRED STRAIN MICE. IN TERMS OF LOW DOSE INTERLEUKIN-2 WE SAW EFFECT ACROSS THE BOARD SO IN TERMS OF THERAPEUTIC THE FACT WE DIDN'T SEE A SEX DIFFERENCE IN THAT REGARD, BUT, YOU KNOW, WE ALWAYS HAVE KEEP IN MIND I THINK EVERY EXPERIMENT THAT WE RUN WE ALWAYS RUN LIKE MALE AND FEMALE IN PARALLEL. >> THANK YOU. FROM DR. KOROSHETZ, INTERLEUKIN-2 IS KNOWN TO HAVE A DOSE-RESPONSE, PREDICTS THAT CHEMOTHERAPY AND INTERLEUKIN-2 COULD INDUCE HEADACHE. COULD YOU COMMENT ON THAT? >> RIGHT, RIGHT. SO, YEAH, ACTUALLY INTERLEUKIN-2 WAS FDA APPROVED TO TREAT CANCER, SO THAT IS FOR HIGH DOSE INTERLEUKIN-2. THAT ACTUALLY IS A PROBLEM WHEN WE'RE TRYING TO DO LIKE, YOU KNOW, CLINICAL TRIALS FOR LOW DOSE INTERLEUKIN-2 BECAUSE YOU HAVE TO HAVE PHARMACIST ON SITE TO DO THE INTERLEUKIN-2 TO THE DOSE THAT WE WANT. 1,000 TIMES DILUTION, IF I REMEMBER CORRECTLY, SO, YOU KNOW, THE INTERLEUKIN-2 DOSE FOR CANCER TREATMENT IS TARGETING FOR THE EFFECTOR T CELLS TO KILL CANCER CELLS BUT LOW DOSE IS TRYING TO NOT -- NOT TRYING TO TARGET TREG CELLS PREFERENTIALLY WITHOUT ACTIVATING THESE ACTIVATED T CELLS, AT LEAST THAT'S IT THE HOPE. SO, YEAH, WE'RE TALKING ABOUT VERY LOW DOSE. ANOTHER QUESTION THAT COME UP WHEN WE TALK TO HEADACHE SPECIALISTS ABOUT THE POTENTIAL CLINICAL TRIAL IS ACTUALLY THEY BRING UP THE ISSUE THAT BECAUSE INTERLEUKIN-2 HAS TO BE INJECTED DAILY, AT LEAST FIVE DAYS, FIVE DAYS CONSECUTIVE, THEY THINK THAT IS A BIG OBSTACLE FOR RECRUITING PATIENTS BECAUSE NOT THAT MANY PEOPLE WOULD LIKE TO COME TO THE OFFICE LIKE EVERY DAY FOR FIVE DAYS TO RECEIVE INJECTIONS. THAT ACTUALLY, YOU KNOW, MAKES US MORE MOTIVATED TO TEST THESE LONGER-ACTING INTERLEUKIN-2. >> EXCELLENT. THANK YOU VERY MUCH. EXCELLENT ANSWER. IS THERE ANY QUESTIONS FOR MARCO OR THE -- FROM MARCO OR THE PANELISTS THAT YOU WANT TO POST TO THE REST OF THE GROUP? >> THERE WAS ONE QUESTION FROM A PANELIST ABOUT MONOCLONAL ANTIBODIES, REDUCING OVERDOSE. SO THE QUESTION IS FROM ROBERT, THERE ARE SOME DATA SUGGESTING SOME OPIOIDS IS NOT REVERSED BY NALOXONE, AND IS ASKING IF WE HAVE DATA ABOUT REVERSAL AND POTENTIALLY EQUIVALENT OR SUPERIOR TO NALOXONE IN THE CHEST RIGIDITY AND SO AS FAR AS LIKE I'M CONCERNED IN OUR STUDIES WE'VE SEEN THAT REVERSAL BRACHYCARDIA, LOOKED AT CHEST VOLUME, AND SOME OTHER SURROGATE DID NOT DIRECTLY LOOK LIKE EMG BUT ALSO BELIEVE OTHER GROUPS IN OUR SPACE HAVE SHOWN SOMEWHAT OF A POTENTIAL EFFECT IN REVERSING EFFECTS THAT ARE KNOWN OPIOID MEDIATED SO I BELIEVE THERE IS LIKE POTENTIAL, POTENTIAL FOR THAT. >> THANK YOU. MARCO, SINCE YOU ASKED, I'LL FOLLOW WITH A DIFFERENT ONE. YOU MENTIONED BIOMARKER STUDY YOU WERE DOING IN PARALLEL WITH YOUR THERAPEUTICS DEVELOPMENT STUDY. CAN YOU TALK ABOUT THE ROLE FOR THAT? YOU MENTIONED PATIENT SELECTION FOR THE CLINICAL TRIALS. IS THERE ANOTHER ROLE YOU HAVE FOR THE BIOMARKER AND COULD IT BE MORE APPLICABLE TO OTHER STUDIES? AND THEN THE OTHER PANELISTS, IF YOU COULD ALSO DISCUSS THE NEED OR ANY PROGRESS IN DEVELOPING BIOMARKERS FOR A PAINFUL CONDITION OR IN PARALLEL WITH YOUR THERAPEUTICS DEVELOPMENT PROJECTS. >> YES, SO SOME I SHOWED TODAY LOOKING AT IMMUNOLOGICAL BIOMARKER, WHEN WE STARTED PROGRAM WE ARE KIND OF LIKE IN NARROW VIEW, IF YOU WILL, LOOKING AT OPIOID-SPECIFIC B CELLS AND OTHER IMMUNE TARGETS AND HOW THAT WOULD PREDICT VACCINE EFFICACY SO WITH THE IDEA OF LIKE APPLYING THAT TO THE CLINICAL TRIAL FOR THE OXYCODONE VACCINE AND OTHER VACCINES IN THE SPACE, BUT BEFORE DOING THAT SINCE FOR PRIOR TO INITIATE STUDY ACCESS TO IMMUNIZED PATIENTS, WE SIMPLY ASKED THE QUESTION OF COMPARING NAIVE VERSUS SUBJECTS WITH USE DISORDER AND ASKED IF WE COULD FIND A SIGNAL. THE FOCUS WAS STILL IN THE CONTEXT OF VACCINES BUT THEN AS WE COLLECT MORE DATA AND WE'RE SEEING MORE OF THIS DIFFERENCE, NOW I START LOOKING AT THIS AS SOMETHING THAT GOES BEYOND VACCINES, SO FOR EXAMPLE IF WE IDENTIFY SPECIFIC CYTOKINES THAT ARE MODIFIED OR LIKE ASPECTS, THOSE PROBABLY COULD NOT JUST BECOME A BIOMARKER FOR THE VACCINE BUT ALSO BIOMARKER OF DISEASE AND POTENTIALLY PHARMACOLOGICAL TARGETS FOR OTHER INTERVENTION. SO FOR EXAMPLE DR. CAO'S TALK SHOWED INTERVENTION BASED UPON INTERLEUKIN-2, SPENT QUITE A BIT SOME TIME LOOKING AT MANIPULATORS OF THE IL-4, 13 PATHWAY, WE HAVE OPPORTUNITY TO LOOK AT NEW ONES, I WONDER IF MANIPULATION OF THE PATHWAYS COULD HAVE SOME VALUE EITHER IN PAIN OR ADDICTION, AND SO I THINK THIS IS JUST SORT OF SCRATCHING THE SURFACE BUT ALSO OTHER PEOPLE LOOKING AT SIMILAR CYTOKINE PROFILES IN DIFFERENT POPULATIONS. SO IT WOULD BE NICE TO ALSO DO THIS IN COLLABORATION, WITH OTHER HEAL-FUNDED INVESTIGATORS, SO WE CAN EXPAND OUR POPULATION BASE, NOT TO BE TOO LONG WINDED, APPRECIATED COLLECTING CLINICAL SUBJECTS IN THE PAST YEAR ESPECIALLY WITH COVID IS NOT EXACTLY SIMPLE. SO CREATING LIKE EITHER INITIAL REPOSITORY WHERE MULTIPLE GROUPS FEED INTO THE PIPELINE AND CAN HAVE MULTIPLE SAMPLES FOR DIFFERENT CLINICAL POPULATIONS SO WE CAN EXPAND THE SEARCH. I THINK THERE'S LOTS OF POTENTIAL THERE. >> SURE. >> JUST TO ELABORATE ON WHAT MARCO IS DESCRIBING, JUST FOR THE BENEFIT OF PEOPLE IN THE AUDIENCE NOT FAMILIAR WITH VACCINE HISTORY, THE REASON THE BIOMARKERS ARE SO INCREDIBLY IMPORTANT IS THAT THERE WERE, YOU KNOW, COCAINE AND NICOTINE VACCINES THAT MADE IT TO PHASE 3 TESTING, AND BOTH OF THEM FAILED ACTUALLY BECAUSE OF JUST TOO LARGE INDIVIDUAL VARIABILITY, AND THE ANTIBODY RESPONSE. SO THE IDEA IS THAT WE'RE HOPING THAT WE CAN IDENTIFY PEOPLE BEFORE THEY ARE VACCINATED WHO MIGHT BE GOOD VACCINE RESPONDERS. SO WITH BOTH NICOTINE AND COCAINE VACCINES THE ONES THAT GENERATED HIGH ANTIBODY LEVELS SHOWED REDUCTIONS IN USE OF NICOTINE AND COCAINE. SO IF WE CAN IDENTIFY THAT GROUP OF PEOPLE, YOU KNOW, BEFORE THEY EVEN GET VACCINATED, THEN WE CAN HAVE AN ENRICHED POPULATION POTENTIALLY WHO MIGHT BE, YOU KNOW, GOOD VACCINE RESPONDERS. SO THAT'S KIND OF WHAT WE'RE HOPING THAT WE'LL BE ABLE TO IDENTIFY. >> THANKS, SANDY. DR. CLARK, SO THE B CELLS THAT YOU'RE LOOKING AT, OR THE SERUM YOU'RE LOOKING AT EXCHANGING, LOOKS LIKE THERE COULD BE A MARKER OR AT LEAST SOMETHING WE CAN QUANTIFY WHICH TRANSFER IN THE PAIN BETWEEN ONE ANIMAL AND ANOTHER. >> YEAH, SIMPLISTICALLY THE BIOMARKERS ARE -- IT WOULD BE CUMBERSOME AND OLDTIME ASSAY, HE COULD DO A SERUM TRANSFER STUDY TO AN ANIMAL, THAT'S HOW WE'RE TRYING TO TRANSLATE THIS BETWEEN SPECIES BUT IT IS A BIOLOGICAL SAMPLE BEING USED TO IDENTIFY THE PRESENCE OF THIS PRO NOCICEPTIVE STUFF. WHAT WE'RE TRYING TO ASSEMBLE IS AUTOANTIGENS. THE PROBLEM IS THERE AREN'T A LOT OF GREAT CANDIDATES FOR THIS. TRY AS WE HAVE, IT'S NOT THAT THERE IS A SINGLE PROTEIN BEING ATTACKED. WE HAVE NO EVIDENCE. THIS IS MUCH BROADER, A SORT AUTOIMMUNOLOGYICAL. NEVERTHELESS THE PROPER PANEL MIGHT ALLOW YOU TO SCREEN PATIENTS FOR THE LIKELIHOOD OF HAVING CONTRIBUTING ANTIBODIES WHICH THEN MIGHT HELP JUSTIFY RISKY OR EXPENSIVE THERAPY. SO THE BIOMARKER IDEA IS VERY MUCH IN LINE WITH OUR GOALS. >> EXCELLENT. ANYBODY ELSE WANT TO DISCUSS BIOMARKERS AND THEIR PROGRAM AT ALL? >> YEAH, I TOTALLY AGREE. I THINK, YOU KNOW, IN TERMS OF CHRONIC HEADACHE TREATMENT I THINK HAVING A BIOMARKER IS EXTREMELY IMPORTANT, ESPECIALLY IN PREDICTING THE TREATMENT OUTCOME LIKE SANDRA SAYS. THE REASON WE GO TO INTERLEUKIN-2 AND TREG WE CAN BYPASS THIS STEP, YOU KNOW, JUST TO HAVE A MORE GENERALIZED TREATMENT. BUT I THINK AT THE END OF THE DAY, YOU KNOW, WHAT YOU REALLY WANT IS STILL THE PRECISION MEDICINE, RIGHT? TO DIRECT THE PATIENT TO THE, SAY, CYTOKINE ANTIBODY THAT WOULD WORK FOR THEM. YEAH, SO IN THAT REGARD I THINK BIOMARKER HAS TO BE CO-EVOLVED ALONG WITH TARGET VALIDATION, ALL THESE RESEARCHES. >> VERY IMPORTANT POINT. PAUL? >> YEAH, THE BIOMARKER WE'RE WORKING IS HOPEFULLY REFLECTION OF TARGET ENGAGEMENT, AUTONOMIC NERVOUS SYSTEM TRANSLATION. WE FOUND ONE OF THE WAYS WE THINK THE MEDIAL HABENULA IS REGULATING BEHAVIORAL RESPONSES TO DRUGS OF ABUSE IS VIA THESE POLY SYNOPTIC PROJECTIONS INTO SYMPATHETIC AND PARASYMPATHETIC NEURONS SO IF WE MODULATE HABENULA FUNCTION WE CAN GET QUITE STRIKING CHANGES IN PERIPHERAL PHYSIOLOGIC RESPONSES THAT REFLECT CHANGES TO SYMPATHETIC TRANSMISSION. BLOOD GLUCOSE, UNDER THE CONTROL OF GLUCAGON AND SYMPATHETIC TRANSMISSION. SO THE WAY WE'RE HOPING OBVIOUSLY IT'S MARKEDLY DISRUPTED PARTICULARLY IN WITHDRAWALS, THE ONES MORE SENSITIVE TO HABENULA-FOCUSED DRUG AND TRACKING CHANGES GIVING US THE IDEA THE DRUG IS HITTING THE TARGET IN VIVO. >> EXCELLENT POINTS. OKAY. >> ALSO SOMEBODY WAS TALKING ABOUT SIDE EFFECTS, IMPORTANCE OF LOOKING INTO, FOR EXAMPLE LIKING IN BIOLOGICS, FOR EXAMPLE INTERLEUKIN, ANTIBODIES OR B CELL OR T CELL AUTOIMMUNE OR AUTORESPONSES AGAINST THE PRODUCT, ACTUAL BIOLOGICS. SO BIOMARKERS COULD POTENTIALLY HAVE A ROLE IN SCREENING THOSE PATIENTS MORE LIKELY DOWN THE YEARS DEVELOP A RESPONSE THAT WOULD PREVENT THE BIOLOGIC TO WORK WHILE OTHERS MAY NOT. AND SO SIMPLE LIKE AUTOANTIBODIES AGAINST MONOCLONAL OR INTERLEUKIN TO PREVENT FURTHER REPEATED FORMULATION THAT COULD BE IMPORTANT, COULD HAVE APPLICATION BEYOND ADDICTION AND PAIN CERTAINLY. >> GOOD POINTS. I'LL SHIFT TO A DIFFERENT TYPE OF QUESTION HERE FOR THE PANEL. AND ASK, YOU KNOW, WHAT KIND OF GAPS IN POTENTIAL FUNDING MECHANISMS DO YOU SEE? WHAT PART OF THE RESEARCH THAT YOU'RE DOING, YOU DON'T SEE AN AVENUE FOR FUNDING, IS THERE OPPORTUNITIES FOR ACCELERATING IT THAT YOU THINK THAT FUNDING OPPORTUNITIES FROM NIH COULD BE HELPFUL? I'LL LEAVE IT FOR ANY OF YOUR GUYS TO ANSWER, OR SOMEBODY FEEL FREE TO TYPE A SUGGESTION IN THE QUESTION AND ANSWER AREA. EVERYBODY ALWAYS WANTS MORE MONEY, I GOT THAT. >> YOU HAVE MONEY, BOY, YOU'RE GOING TO FINDS SOME APPLICATIONS COMING IN, I'M SURE. >> TRUE. >> I THINK THAT -- I WILL POINT OUT THIS IS SPECIFIC TO MY OWN NARROW HORIZON, BUT TRANSLATION IS REALLY A KEY AREA THAT I'VE FOUND INTIMIDATING TO APPROACH. SO I THINK THERE IS HELP AVAILABLE FOR MANY TYPES OF LABORATORY STUDIES, MAYBE NOT ENOUGH, BUT WHEN WE GET TO THAT POINT OF WANTING TO DO SOMETHING EARLY PHASE OR PROOF OF CONCEPT, THAT'S REALLY AN AREA WHERE I THINK BOTH FINANCIAL RESOURCES ARE IMPORTANT BUT ALSO INTELLECTUAL ONES, THOSE THAT PARTNER WITH INDUSTRY TO UNDERSTAND WHAT IS FEASIBLE, WHAT THE NEXT STEP WOULD BE. I THINK NIH DOES SOME OF THAT. I'M JUST UNFAMILIAR WITH IT. BUT TO EMPHASIZE THE AVAILABILITY OF THAT KIND OF HELP, BE IT FINANCIAL OR INTELLECTUAL OR ORGANIZATIONAL, IT WOULD BE ESSENTIAL TO SOME OF THESE THINGS MAKING IT EVENTUALLY TO -- >> ON THE CURRENT SLIDE THAT'S UP THERE, UNDER THE THIRD MAIN CHECK, RFA NF 21, LATE STAGE, SOME BIOLOGIC PREPARING FOR YOUR IND FILING. FOR THOSE TYPE OF PROJECTS WE BUILD CONSULTANT TEAM TO HELP THE RESEARCHER AND GIVE THEM ACCESS TO CONTRACTS WITH CROs, WHICH HAVE TREMENDOUS AMOUNTS OF EXPERTISE IN FORMULATION, TOXICOLOGY TESTING, PK/PD STUDIES, ET CETERA, WE DO SEE THAT AS A NEED. OUTSIDE THE PAIN AREA THERE'S ALSO THE BLUEPRINT NEUROTHERAPEUTIC PROGRAM, THIS RFA IS FASHIONED AFTER. THAT'S A GREAT POINT YOU BRING UP. SOMETIMES ACADEMICS NEED THAT EXTRA HELP OF CONSULTANTS OR ACCESS TO COMPANIES THAT JUST DO THIS WORK WELL, TRANSLATIONAL RESEARCH. YEAH, THAT'S A GREAT POINT. ANYBODY ELSE? >> JUST TO ELABORATE ON THAT POINT, DAVE, I COMPLETELY AGREE THAT THAT IS A CRITICAL QUESTION. I KNOW THERE ARE MANY PEOPLE AT NIDA WHO ARE INTERESTED IN THIS TOPIC. BUT, YOU KNOW, THERE'S TRANSLATION FROM -- AT ALL LEVELS, RIGHT? I THINK YOU'RE TALKING MAYBE ABOUT PRE-CLINICAL TO CLINICAL TRANSLATION, ALSO WITHIN THE CLINICAL AREA THERE'S HUMAN LAB TO, YOU KNOW, CLINICAL TREATMENT TRIAL TO, YOU KNOW, LIKE CTM-TYPE STUDY, IN THE GENERAL POPULATION. AND THERE ARE PITFALLS ALL ALONG THAT PROCESS AS WELL. SO I THINK IT WOULD BE -- THESE ARE KINDS OF STUDIES THAT TYPICALLY DON'T RECEIVE FUNDING FROM, YOU KNOW, NIH BECAUSE IT'S NOT NECESSARILY LIKE GROUND BREAKING OR WHATEVER BUT IN TERMS OF DISCOVERY, BUT IN TERMS OF PRACTICALITIES THEY ARE REALLY IMPORTANT. LIKE WHAT, FOR EXAMPLE, I DO A LOT OF LAB-BASED RESEARCH AND WE USE MODELS OF SELF-ADMINISTRATION THAT WERE DEVELOPED IN PRE-CLINICAL LAB. AND SOMETIMES THEY PREDICT PRETTY WELL WHAT HAPPENS IN A TREATMENT TRIAL BUT SOMETIMES THEY DON'T. AND SO IT WOULD BE NICE TO SPEND SOME FUNDS TO REALLY ESTABLISH WHICH PROCEDURES IN THE LAB ARE THE BEST PREDICTIVE OF WHAT HAPPENS IN A TREATMENT AREA. I'M JUST GIVING A PLUG FOR THAT KIND OF STUDY BECAUSE IT'S -- YOU KNOW, LIKE I SAID, IT'S NOT NECESSARILY GROUNDBREAKING BUT IT'S JUST REALLY IMPORTANT PRACTICAL IMPLICATIONS. >> SURE. INSIDE OUR PSPP PROGRAM SCREENING, SO THERE ARE OPPORTUNITIES INSIDE NIH THROUGH A CONTRACT THAT WE HAVE. THAT'S THE PLATFORM SCREENING PROGRAM FOR PAIN, PSPP PROGRAM. MARCO, THERE WERE A FEW QUESTIONS ADDRESSED TO YOUR PROJECT. WAS THERE CONCERN FOR WITHDRAWAL WITH THE MONOCLONAL ANTIBODIES? >> YEAH, SO NOT -- WE TEST WITH VACCINES AND MONOCLONALS, SELF-ADMINISTRATION STUDIES OR STUDIES WHERE WE GIVE FENTANYL AND THEN NALOXONE, WITH MONOCLONAL ANTIBODIES WE DID NOT SEE ANY EVIDENCE OF WITHDRAWAL, SO WE DON'T REALLY BELIEVE THAT. ALSO OTHER INVESTIGATORS IN THE NICOTINE FIELD FOR INSTANCE HAVE SHOWN SIMILAR STUDIES, SO WE DON'T BELIEVE THAT CROSSING THE BLOOD-BRAIN BARRIER, FAST ENOUGH FOR THE RECEPTOR SO WE JUST DON'T SEE ANY EVIDENCE OF THAT. THAT WAS A GREAT QUESTION. THAT'S A GREAT CONCERN FOR TRANSLATION. >> CAN YOU ELABORATE ON THE FOCUS OF GOOD RESPONDERS FOR VACCINES? IS THIS FOR THE PURPOSE OF DEVELOPMENT OR WOULD THERE BE SOME COMPANY'S DIAGNOSTIC TOOL TO HELP DETERMINE WHO SHOULD RECEIVE THE VACCINES POST-APPROVAL, LET'S CALL THAT PATIENT SELECTION. >> THAT'S ALSO A GREAT QUESTION. I WOULD SAY BOTH. THE NEED FOR EVIDENCE, FOR RESPONSE, COULD HAVE LIKE INPUT ON DEVELOPMENT, SO EVEN IN ANIMAL MODELS BEING ABLE TO IDENTIFY GOOD RESPONDERS BUT IN CLINICAL TRIALS, MAYBE NOT IN PHASE 1 BUT IF YOU DO PATIENT STRATIFICATION IN PHASE 2 AND PHASE 3 THAT COULD HELP TO ENROLL THE RIGHT TARGET POPULATION. AND THEN AS FAR AS CLINICAL IMPLEMENTATION, COMMERCIALIZATION, COMPANION DIAGNOSTIC DEFINITELY WOULD HELP TO IDENTIFY THOSE PATIENTS THAT WOULD RESPOND, AND THEN OBVIOUSLY WE HAVE TO SEE THE ECONOMICAL FEASIBILITY OF HAVING A COMPANION DIAGNOSTIC, FOR EXAMPLE FOR SOME OF THE CANCER TREATMENT COMPANION DIAGNOSTICS ARE PRETTY MUCH STANDARD FOR SOMETHING LIKE ADDICTION, I DON'T KNOW HOW THAT WOULD ACTUALLY TRANSLATE INTO THE COMMERCIAL SPACE BUT THAT WOULD BE THE IDEA OF USING A COMPANION TICKET. I MEAN, COMPANION DIAGNOSTIC. SO WE'VE DONE A LOT OF WORK WITH FLOW CYTOMETRY, IT'S NOT A GOOD DIAGNOSTIC COMPANION ASSAY BUT IF YOU ARE LOOKING AT CYTOKINES OR SOME OTHER LIKE QUICK KIND OF LIKE BLOOD DROP, A FEW MINUTES, THAT COULD BE ECONOMICALLY FEASIBLE AND IMPLEMENTED IN THE CLINIC. >> THANKS, MARCO. WE HINTED ON EARLIER, AND SANDY MADE A GREAT POINT, ABOUT SOME OF THE SHORTCOMINGS OF THE SMALL ANIMAL MODELS, AND THE LARGE MODELS. CAN WE DISCUSS THIS A LITTLE MORE AND SAY ANY THOUGHTS ON THE DISEASE MODELS OR PARTICULAR OUTCOME MEASURES IN THOSE MODELS THAT CAN HELP IN US SPEEDING THE DEVELOPMENT OF A THERAPEUTIC TO THE CLINIC OR HELPING IN THE PREDICTION OF WHETHER OR NOT IT WOULD BE HELPFUL? I'M ASKING TO TALK ABOUT IT IN A POSITIVE WAY. THERE'S A LOT OF NEGATIVE THINGS WE COULD SAY, WE HAVE TO USE THE CAVEAT, LET'S HEAR PAUL AND THEN DAVE, MARCO, SANDY. >> YEAH, MY PERSPECTIVE IN ANIMAL PROCEDURES IS THAT THEY CAN BE VERY, VERY USEFUL DEPENDING ON HOW YOU USE THEM OF COURSE. THE ONE PROCEDURE WE USE EXTENSIVELY IN THE LAB IS INTRAVENOUS SELF-ADMINISTRATION BEHAVIOR, SANDY IS VERY FAMILIAR WITH THAT. THERE'S MANY FLAVORS OF ADMINISTRATION AND YOU CAN USE IT IN WEIRD AND WONDERFUL WAYS. YOU CAN ASK VERY INTERESTING QUESTIONS. THE QUESTION IS THE DATA YOU SELECT RELEVANT TO THE HUMAN DISEASE, HUMAN CONDITIONS YOU'RE TRYING TO ADDRESS? AND SO I'D LIKE TO KEEP IT SIMPLE. I KNOW ONE OF THE MOST REPRODUCED FINDINGS IN PSYCHIATRY, GENETICS OF PSYCHIATRY, TO FIND THE ALLELE IN THE NICOTINIC RECEPTORS INCREASES SUSCEBILITY TO TOBACCO RECEPTION. IN THE MICE THE PHENOTYPE WE SEE IS THEY SELF-ADMINISTER MORE DRUG DURING THE SESSION, TRANSLATES FROM HUMAN GENETICS INTO HOUSE. -- MOUSE. I'VE GOT CONFIDENCE WHAT I SEE IN MOUSE AND RAT IS RELEVANT TO HUMAN. I THINK WE'LL BE ABLE TO USE ANIMALS IN CLEVER AND BETTER WAYS WHEN WE HAVE MORE HUMAN GENETICS AND MORE HUMAN DATA THAT WE CAN LINK IN TO WHAT WE ACTUALLY SEE IN OUR ANIMALS SO WE JUST NEED MORE HUMAN DATA TO HELP US IN THAT REGARD. >> GREAT POINTS. >> I'LL TAKE A STAB, A FEEBLE ONE, FOR MUSCULOSKELETAL PAIN, HOTLY DEBATED, POORLY UNDERSTOOD. ALLODYNIA MEASURES ARE LIMITED, WE DON'T HAVE TO REVISIT FAILURES IN TRANSLATION THAT LEAD TO CONCERN. WE'RE TURNING WITH HOPE BUT PERHAPS INCOMPLETE JUSTIFICATION AT THIS POINT TO FUNCTIONAL ONES. WE SPEND TIME DOING PLACE PREFERENCE STUDIES, PUTTING ANIMALS ON RUNNING WHEELS. I WOULD SAY JUST TO BE HONEST WITH THE COMMUNITY WE FOCUSED ON PLACE PREFERENCE, I DON'T THINK TO DATE WE'LL HAVE SEEN SOMETHING IN PLACE PREFERENCE WE DIDN'T SEE LOOKING AT ALLODYNIA. IT DOESN'T MEAN THAT WILL ALWAYS BE THE CASE BUT WE'RE MORE INTERESTED NOW IN FUNCTION BECAUSE PART OF MY WORK IS WITH THE V.A., REHABILITATION EMPHASIS HERE IS LARGE. AND I THINK WE CAN JUSTIFY FUNCTIONAL ENDPOINT THAT OVERLAPS WITH PAIN, LEARNING IN THE COURSE OF OUR "HEAL" STUDIES WHETHER THEY GIVE US THE SAME ANSWER, PUT ANIMALS ON WHEELS AND ASK THEM TO DO TASKS, AS WE WOULD HAVE GOTTEN DOING SOMETHING SIMPLER. WE'RE TRYING TO CIRCUMVENT BY GOING TO THE DOGS, A DIFFERENT SPECIES, SORT OF GETTING -- UNASKING THE QUESTION AND GOING AROUND IT BUT THAT'S OUR FORTUNE. >> DR. COU, DO YOU WANT TO COMMENT ON HEADACHE MODELS? >> PARTICULARLY WEEK IN THIS REGARD, NO WAY WHETHER WE KNOW THEY HAVE A HEADACHE OR NOT. IN A WAY, EVERYTHING WE LOOK AT HAS TO BE INFERRED. WE SORT OF LEARNED TO DEAL WITH THAT. I COMPLETELY AGREE, WITH DAVE CLARK, A SINGLE REFLEX TO HAVE STRENGTH BECAUSE IT'S ROBUST. ROBUST IS WHAT WE'RE LOOKING FORWARD IN THE TEST. ANOTHER THING IS I THINK MORE AND MORE KNOWLEDGE THAT WE KNOW ON THE SPECIES DIFFERENCE BETWEEN, SAY, MOUSE AND HUMANS, LIKE HOW CGRP IS EXPRESSED, P33 DIFFERENTIALLY EXPRESSED, WITH ALL THE BACKGROUND KNOWLEDGE, VALIDATE BEHAVIOR AND SETTLE DATA WE COLLECT FROM MICE AND TRY TO VALIDATE, AND THAT WILL, YOU KNOW, ACTUALLY MAKE THE MOUSE WORK MORE TRANSLATABLE IN THE FUTURE. >> GOOD POINTS. SANDY, IN THE CASE OF COMPOUND THAT YOU GUYS HAVE, PRETTY LATE DEVELOPMENT, YOU SHOW DATA FOR THE TAIL FLICK. I WAS WONDERING IF THAT MATCHES THE TARGET POPULATION YOU'RE LOOKING FOR WITH THE COMPOUND OR IF YOU HAVE SOME OTHER ANIMAL MODEL DATA THAT YOU DIDN'T HAVE TIME TO SHOW? >> I MEAN, THAT WAS PART OF THE GENERAL DEVELOPMENT OF THE COMPOUND. YOU KNOW, THE GRANT THAT WE'RE RUNNING NOW IS FOCUSED ON SUBSTANCE USE DISORDER, NOT ANALGESIA PER SE. THAT WOULD HAVE A WHOLE DIFFERENT KIND OF DEVELOPMENT PROFILE. BUT I JUST WANTED TO GO BACK AND HIGHLIGHT SOMETHING THAT PAUL SAID, WHICH I COMPLETELY AGREE WITH. BASICALLY WHAT HE WAS SAYING IS THAT HE PAYS ATTENTION TO REVERSE TRANSLATION, RIGHT? AND I JUST CAN'T EMPHASIZE THAT MORE. HAVING DONE THE PRE-CLINICAL, YOU KNOW, RESEARCH AND STILL INVOLVED WITH IT NOW, BUT THE -- WHEN I MADE THE JUMP FROM PRE-CLINICAL TO CLINICAL, THERE'S A WHOLE HOST OF FACTORS THAT ARE IN PLAY WITH, YOU KNOW, THE DISORDER. SUBSTANCE USE DISORDER, OPIOID USE DISORDER. THAT ARE JUST NOT CAPTURED IN THE ANIMAL MODELS. I HEAR WHAT, YOU KNOW, DR. CAO AND DR. CLARK ARE SAYING ABOUT WANTING TO HAVE THE SIMPLE MODELS AND I GET THAT BECAUSE IT JUST MAKES IT EASIER TO DO THE STUDIES THAT WILL GIVE US A SIGNAL BUT ON THE OTHER HAND, YOU KNOW, FOR EXAMPLE, I WAS INVOLVED IN DOING ANALGESIC -- ANALGESIA RESEARCH WITH THE DELTA SUBTYPE OF OPIOID RECEPTOR, FOR EXAMPLE, AND, YOU KNOW, I DID A LOT OF ANALGESIA TESTS WAY BACK WHEN, WHEN I WAS IN GRADUATE SCHOOL, AND, YOU KNOW, USED ALL THE USUAL MODELS, TAIL FLICK TEST, AND WITHOUT REALLY PAYING ATTENTION TO THE FACT THAT IN THE PAIN WORLD YOU GIVE THESE ANALGESICS IN PEOPLE WHO ARE EXPERIENCING PAIN, RIGHT? PAIN IS ALREADY THERE. WHEREAS I WAS USING NAIVE ANIMALS TO ASSESS ANALGESIC EFFECTS OF COMPOUNDS, AND THEY HAVE VERY DIFFERENT EFFECTS POTENTIALLY, IN AN ANIMAL ALREADY IN CHRONIC PAIN VERSUS NAIVE ANIMAL. AND WITH SUBSTANCE USE DISORDERS, IT'S THE SAME THING. IT'S LIKE THE MEDICATIONS THAT WE'RE DEVELOPING FOR SUBSTANCE USE DISORDERS WILL MORE LIKELY THAN NOT BE GIVEN REPEATEDLY, WHERE AS A LOT OF STUDIES THAT WERE DONE PRE-CLINICALLY ARE ACUTE ADMINISTRATION TO SEE IF YOU GET A SIGNAL. IF YOU DO, THAT'S GREAT. BUT I REVIEWED GRANT APPLICATIONS WHERE THEY HAVE GIVEN IT REPEATEDLY AND YOU SEE A VERY QUICK TOLERANCE TO THAT EFFECT. AND THAT WOULD NOT BE VERY USEFUL IN A CLINICAL SITUATION. SO, AND THEN I GUESS ANOTHER AREA THAT WE'VE TALKED ABOUT IN THIS, YOU KNOW, MEETING, THIS CONFERENCE, IS POLYSUBSTANCE USE, RIGHT? THAT'S THE NORM IN SUBSTANCE USERS. IT'S LIKE, YEAH, YOU GET PEOPLE WHO ARE ONLY OPIOID USERS, BUT MORE OFTEN THAN NOT PEOPLE ARE USING COMBINATIONS OF OPIOIDS AND STIMULANTS AND ALCOHOL AND BENZOS. WE DON'T REALLY CAPTURE THAT VERY WELL AT ALL IN THE PRE-CLINICAL AREA. SO I GUESS FOR PEOPLE WHO ARE DOING A LOT OF THE PRE-CLINICAL RESEARCH I URGE YOU TO PAY ATTENTION TO SOME OF THOSE IMPORTANT FACTORS AND DO THE -- TRY TO REVERSE TRANSLATION TO DEVELOP MODELS THAT MORE ACCURATELY REFLECT WHAT DRUG USERS ARE DOING. >> YEAH, I COMPLETELY AGREE. I THINK THAT'S A REALLY GOOD POINT. ONE ADDITIONAL THING ABOUT THE ANIMAL MODEL THAT BOTHERED ME IS ACTUALLY HOW ROBUST THESE MODELS ARE. YOU KNOW, LIKE IN THE WORLD OF MIGRAINE HEADACHE, NOT EVERYONE RESPONDS TO THE SAME TRIGGER. YOU ALWAYS HAVE RESPONDERS AND NON-RESPONDERS BUT WHENEVER WE HAVE A NEW MODEL, THE MORE OFTEN THAN KNOW WE SEE HOW ROBUST THIS MODEL IS WHICH IS GREAT, BUT THEN I'M CRAVING FOR A MODEL WHICH WE HAVE RESPONDERS VERSUS NON-RESPONDERS, YOU KNOW, THIS TO ME IS MORE CLOSER TO THE REAL WORLD SITUATION IN WHICH WE CAN ACTUALLY TEST, YOU KNOW, DRUGS, DIFFERENT EFFECTS OF DRUGS, SO ON AND SO FORTH. >> OKAY. SO MAYBE WE CAN DO ANOTHER PIVOT AND SHIFT AND TALK ABOUT IRB AND FDA REGULATORY PATHWAYS AND THERAPEUTICS DEVELOPMENT FOR OPIOID USE DISORDER OR FOR PAIN, SOME HURDLES YOU'RE SEEING AT LEAST IN THE GROUPS DOING THE PRE-CLINICAL RESEARCH. HOW ARE YOU PLANNING FOR THOSE SUBMISSIONS AND THOSE QUESTIONS YOU EXPECT TO HEAR FROM THE FDA? SANDY, YOU PROBABLY HAVE THE MOST EXPERIENCE HERE, IF YOU WANT TO ADDRESS THAT. >> YEAH, IT'S HARD. >> I'M SORRY, IT'S NOT AN EASY QUESTION. THAT WAS NOT A SOFTBALL. >> NO, IT'S JUST NAVIGATING THE PROCESS IS VERY COMPLICATE AND DIFFICULT. HAVE YOU TO BE VERY PERSISTENT. YOU WANT TO SAY SOMETHING. >> NO, IT'S SOMETHING WE'RE DEALING WITH RIGHT NOW. >> IS IT A CONSULTANT, MAKING SURE YOU HAVE SOMEBODY ON THE TEAM THAT'S GONE THROUGH THE PROCESS MULTIPLE TIMES? HOW ARE YOU DOING IT FROM A PRACTICAL LEVEL? >> NIDA'S FANTASTIC. THEY HAVE A WHOLE REGULATORY BRANCH, BOB HAS BEEN WITH NIDA FOR A LONG TIME, AND FOR THE ACADEMIC RESEARCHERS THEY ARE A FANTASTIC RESOURCE I WOULD SAY. THEY ACTUALLY EVEN GO TO FDA MEETINGS, STAY SILENT IN THE BACK GROUND BUT MAY HELP US INTERPRET WHAT THE FDA IS SAYING. YOU KNOW, WITH DRUG COMPANIES WHO HAVE EXPERIENCE WITH THE PROCESS AND THEY HAVE A REGULATORY TEAM, IT MAKES IT EASIER BUT NOT ALL COMPANIES ARE LIKE THAT. GETTING REGULATORY HELP THROUGH NIH OR THROUGH THE COMPANY'S REGULATORY TEAM IS JUST REALLY CRITICAL. THE IRB PROCESS IS SORT OF THE -- YOU KNOW, IT'S A WHOLE DIFFERENT THING. IT'S RELATED OF COURSE BUT I THINK THE FDA REGULATORY APPROVAL IS WHERE IT REALLY GETS IMPORTANT TO GET INPUT FROM REGULATORY EXPERTS I WOULD SAY. >> HOW ABOUT BALANCING PATIENT SELECTION WITH, YOU KNOW, DEVELOPING A THERAPEUTIC THAT CAN WORK FOR A LOT OF PATIENTS? LET'S SAY IT THAT WAY. I SAW SOME DEVELOPMENT YOU'RE DOING, MARCO DOING A BIOMARKER MORE PATIENT SELECTION PROBABLY THINKING ABOUT THAT ALSO WITH YOUR COMPOUND, SANDY, ON THE FRONT END. HOW DO YOU -- AND PAUL. WHO ARE THE RIGHT PATIENTS FOR THIS THERAPY? >> WELL, THAT'S WHERE, YOU KNOW, HAVING SOME REGULATORY HELP IS REALLY IMPORTANT. FOR EXAMPLE, WITH THE OXYCODONE VACCINE I'M WORKING ON WITH MARCO, WE DESIGNED OUR PHASE 1 STUDY IN A PRE-IND MEETING TO BE LIKE THE NORMAL HEALTHY VOLUNTEERS, SINGLE DOSES, TO GET A SENSE OF SAFETY AND PRELIMINARY EFFICACY. THE FDA SAID IN VERY STRONG LANGUAGE NO WAY. YOU CANNOT TEST THIS VACCINE IN A NORMAL HEALTHY VOLUNTEER POPULATION. YOU HAVE TO DO IT IN OPIOID USERS WHICH IS OBVIOUSLY MORE COMPLICATED. AND SO WE HAD A LOT OF BACK AND FORTH AND DISCUSSED WITH NIDA AND CAME UP WITH A PLAN THAT ULTIMATELY THE FDA ACCEPTED BUT IT'S -- YEAH, IT'S HARD. DID YOU INCLUDE OUTCOME SAFETY MEASURES? >> THIS IS WHERE THE ACADEMIC ME AND THE INDUSTRY EXPERIENCE ME COLLIDE BECAUSE AS AN ACADEMIC, WITH PRIMARILY (INDISCERNIBLE) I TRY TO MAXIMIZE AMOUNT OF INFORMATION I COLLECT WHEREAS I KNOW IN STANDARD PHASE 1 STUDIES YOU DON'T INCLUDE ANY KIND OF EFFICACY ENDPOINTS, RIGHT? IT'S JUST SORT OF NOT DONE WHICH I DON'T COMPLETELY UNDERSTAND WHY. I THINK IT HAS TO DO WITH STATISTICAL ANALYSES, BUT -- AND SO WE ENDED UP PROPOSING PRELIMINARY ENDPOINT EFFICACY IN OUR PHASE 1 STUDY, AND THE FDA ACCEPTED IT. SO I GUESS I WOULD JUST RECOMMEND THAT IF YOU CAN SNEAK IT IN, THEN TRY. TRY TO DO THAT. >> WE'VE SEEN SOME OF THAT ON THE PAIN SIDE, ALSO, THAT THERE'S AN INTEREST IN THAT. IF THERE'S SOMEBODY WHO IS ATTENDING THAT WANTS TO PUT A COMMENT IN THE QUESTION AND ANSWER BOX, FEEL FREE. IS THERE ANYBODY ELSE FROM THE PANEL WHO WANTS TO COMMENT ON PHASE 1 STUDIES AND APPROPRIATENESS OF OUTCOME MEASURES OR JUST TO BE -- SAFETY OR ANYTHING ABOUT THE FIRST-IN-HUMAN STUDIES THAT YOU WANT TO COMMENT ON? >> I WAS GOING TO SECOND SANDY'S POINT. THE NIDA GROUP HAVE BEEN SPECTACULAR BECAUSE OF THE ADVICE THEY CAN OFFER. THEY GOT TREMENDOUS EXPERIENCE AND THEY RAISED ISSUES THAT WE NEVER WOULD HAVE CONSIDERED BECAUSE OF THE EXPERIENCE. IT'S CRITICAL IF YOU'RE MOVING TOWARDS THOSE KIND OF EFFICACY STUDIES THAT YOU GET IN TOUCH WITH THEM AS SOON AS YOU CAN. THEY OFFER WORDS OF WISDOM. ALSO OF COURSE THE OPIOID DEPENDENT INDIVIDUALS THAT WE'VE BEEN LOOKING TO TARGET ARE DIFFERENT. SO AGAIN THE SAFETY STUDIES ARE DIFFERENT. YOU HAVE TO DO YOUR SAFETY STUDIES IN THAT POPULATION. SO IT'S NOT LIKE OTHER TYPES OF DRUG DEVELOPMENT PROGRAMS. YOU HAVE TO SHOW THAT THESE COMPOUNDS ARE SAFE. ALSO THAT THEY DON'T EXACERBATE OPIOID RELEVANT ENDPOINTS LIKE RESPIRATORY, AND NUMBER OF ENDPOINTS AVAILABLE NOT WHAT WE WOULD WANT. FOR EXAMPLE, TYPICAL CLINICAL TRIAL THAT THE FDA WOULD LIKE TO SEE IS PERHAPS NOT THE ONE BASIC SCIENTISTS -- WOULD NOT BE THE ONE I WANT TO DESIGN. PERHAPS WE WANTED TO DEVELOP SOMETHING TO PREVENT RELAPSE, THAT DESIGN IS GOING TO LOOK DIFFERENT FROM TYPICAL DATA PACKAGE THE FDA WILL SEE. THESE ARE ALL HURDLES WE'LL FACE AS A FIELD IN THE COMING YEARS AS WE DEVELOP NEW MEDICATIONS AND DESIGN THOSE MEDICATIONS FOR DIFFERENT ASPECTS OF OPIOID USE DISORDER AND PAIN OF COURSE, MANY HURDLES LIE AHEAD UNFORTUNATELY. >> BIG HURDLES, THAT'S FOR SURE. WE'RE GOING TO JUMP TO A QUESTION THAT CAME FROM THE GROUP OVER HERE. I WAS HOPING OPIOID USE DISORDER PEOPLE COULD ADDRESS IT. IT'S SOMETHING UNDERLYING THAT I'M NOT SURE I'M GETTING. OPIOID USE DISORDER WE HAVE EFFECTIVE MEDICATIONS, FOR SOME PATIENTS THAT'S THE CASE, OTHERS NOT. WHEN IT COMES TO NEW DRUG DEVELOPMENT FOR OPIOID USE DISORDER WOULD COMPOUNDS ULTIMATELY NEED TO BE SUBJECTED TO NON-INFERIORITY TRIALS AGAINST EXISTING MEDICATIONS, HEAD TO HEAD STUDIES, IN ORDER TO REACH MARKET OR TO GET ACCEPTANCE IN THE MEDICAL FIELD? DO YOU THINK HEAD TO HEAD TRIALS ARE NEEDED OR -- YEAH, I'LL LEAVE THAT TO THE PANEL AND SEE WHICH DIRECTION IT GOES. >> I CAN TAKE THIS QUESTION. THANKS FOR POSING IT BECAUSE IT'S A REALLY IMPORTANT ONE. IT DEPENDS ON WHAT KIND OF MEDICATION, WHAT KIND OF MECHANISM IT LAST. I AGREE THAT WE DO HAVE REALLY EFFECTIVE MEDICATIONS, ALL OF THEM HAVE BEEN METHADONE, BUPRENORPHINE, NALOXONE, SHOWN TO BE EFFECTIVE IN SHORTER TERM FOR TREATING THE DISORDER, ALSO FOR PREVENTENING OVERDOSE. SO, IF YOU HAVE AN OPIOID BASED MEDICATION, THEN MAYBE THERE WOULD BE SOME COMFORT AT THE FDA, LIKE ANOTHER FORM OF AGONIST OR ANTAGONIST, SORT OF LIKE THE 333 COMPOUND THAT I TALKED ABOUT. YOU KNOW, IT LOOKS LIKE IT HAS POST PARTIAL AGONIST AND ANTAGONIST TYPE EFFECTS. SO, MAYBE THE FDA WOULD BE MORE COMFORTABLE WITH THAT. YOU KNOW, AND THEY WOULD REQUIRE A NON-INFERIORITY TRIAL BUT FOR SOMETHING LIKE A VACCINE I MEAN I PERSONALLY WOULD BE REALLY NERVOUS ABOUT JUST GIVING THE VACCINE ALL BY ITSELF TO SOMEBODY WHO IS AN OPIOID USER BECAUSE, YOU KNOW, WELL, I SHOULDN'T SAY THAT SO QUICKLY BECAUSE THE VACCINE ALSO -- MARCO HAS SHOWN IT'S EFFECTIVE REVERSING RESPIRATORY DEPRESSIVE EFFECTS OF OPIOIDS, MAYBE IT IS OKAY AND IT IS SAFE FROM THAT PERSPECTIVE. IT CAN BE GIVEN IN COMBINATION WITH BUPRENORPHINE, METHADONE OR NALOXONE, I WOULD FEEL COMFORTABLE STARTING THERE AS AN ADJUNCT TO SEE WHETHER WE CAN INCREASE PERCENTAGE OF PEOPLE WHO ARE, YOU KNOW, RESPONDERS WHO ARE ABSTINENT AFTER SIX MONTHS. USUALLY ABOUT 50% OF PATIENTS WILL RELAPSE AT THE SIX-MONTH MARK, BUT IF A VACCINE IS ON BOARD, YOU KNOW, SOMEBODY WHO IS RECEIVING BUPRENORPHINE IF WE CAN EXTEND THE TIME PERIOD OUT TO A YEAR OR LONGER I THINK THAT WOULD BE A BIG ADVANCE. >> ARE YOU SUGGESTING CLINICAL TRIALS BE DONE IN COMBINATION WITH BUPRENORPHINE TREATMENT? >> UH-HUH. THAT WOULD BE SAFER AND, YOU KNOW, UNTIL WE GET A BETTER HANDLE ON HOW EFFECTIVE SOMETHING LIKE THE VACCINE WOULD BE IN TERMS OF PREVENTING SOMEBODY FROM OVERDOSING. >> LEARNING FROM OTHER FIELDS IF YOU LOOK AT CLINICAL TRIALS IN THE CANCER SPACE OFTEN YOU HAVE YOUR NEW IND, NEW BIOLOGIC OR SMALL MOLECULE OFTEN GIVEN WITH STANDARD TREATMENT, AND SO JUST LIKE IN PRE-CLINICAL STUDIES, FOR EXAMPLE THE VACCINE WITH VIVITROL, WHY NOT DO IT IN THE CLINICAL SPACE AS WELL, ASSURING SAFETY FOR PARTICIPANTS, ALSO ASSURE DEMONSTRATE CLINICAL FEASIBILITY BRINGING NEW THERAPY INTO THE CLINIC, AND THEN THE LAST POINT I WOULD LIKE TO MAKE I DO AGREE SHOWING IT'S COMPARE ANNUAL OR SUPERIOR TO SOMETHING THAT'S ALREADY APPROVED, BUT SOMETIMES CAN BE HARD. FOR EXAMPLE, IF YOU WANT TO DESIGN A STUDY FOR REVERSAL AGENTS OF OVERDOSE THAT WOULD BE TRICKY TO GET APPROVED TO DO THAT. WHEN YOU LOOK AT COMPOUNDS LIKE FENTANYL, FOR INSTANCE, HOW YOU DESIGN THAT, FOR EXAMPLE IF YOU LEARN FROM OTHER FIELDS, LOOK AT, FOR EXAMPLE, ANTIDOTES FOR, I DON'T KNOW, NERVE AGENTS, ET CETERA, SOME OF THOSE PRODUCTS, THEY SHOW SAFETY IN CLINICAL TRIALS BUT THEN THEY DON'T SHOW EFFICACY BECAUSE TEST COMPOUND, NERVE AGENTS OR SOMETHING SIMILAR, TOXIC ENOUGH, WOULDN'T BE GIVEN TO PARTICIPANTS. FOR EXAMPLE YOU COULD GET ANTIDOTE FOR SAFETY BUT ALSO EFFICACY LOTTERY -- WILL BE DONE IN ANIMALS. >> OR LARGE ANIMALS, GET THE MOST AMOUNT OF DATA FROM PRE-CLINICAL MODELS, GOOD POINT. >> SO THAT SHOULD BE ACCOUNTED FOR IN THE STUDIES, EVEN IN ADDICTION SPACE. >> EXCELLENT. SO, WE HAVE JUST A FEW MINUTES LEFT HERE. I WANTED TO LEAVE THESE FEW MINUTES FOR ANYTHING YOU FEEL THE PANEL WANTS TO GIVE OVER TO THE COMMUNITY, ANYTHING THEY WANT TO SAY ABOUT THEIR PARTICULAR STUDY OR HOW "HEAL" CAN ACCELERATE INNOVATION THERAPEUTICS AND THE OPIOID USE DISORDER. HOW ABOUT THE ORDER OF THE SPEAKERS, SANDY, YOU WOULD GO FIRST. >> SURE. I GUESS I JUST WOULD RECOMMEND THAT WE CONTINUE HAVING DIALOGUES BETWEEN THE PRE-CLINICAL AND CLINICAL RESEARCHERS BECAUSE THAT'S SO, SO IMPORTANT. AND CLINICAL TREATMENT PROVIDERS. BECAUSE THAT'S ANOTHER STEP ALONG THE WAY THAT THEY RAISE ISSUES THAT WE DON'T EVEN THINK ABOUT IN THE CLINICAL RESEARCH AREA. LIKE, YOU KNOW, WE CAN TEST A MEDICATION IN THE HUMAN LAB THAT LOOKS GREAT, IT SHOWS A SIGNAL, BUT IT'S JUST NOT WELL TOLERATED IN A CLINICAL POPULATION. SO HAVING DISCUSSIONS LIKE WHAT WE'RE HAVING RIGHT NOW IS SO, SO IMPORTANT. WE NEED TO KEEP DOING IT. >> GREAT POINTS. THANKS. NEXT? >> I GUESS I'M NEXT. >> YEP. >> I'M SORRY FOR THE CIRCUMSTANCES THAT LED TO THE CREATION FIELD IN A WAY BECAUSE THEY ARE SO TRAGIC, BUT THE COHERENCE OF THE PROGRAM I'M OPTIMISTIC WILL PAY DIVIDENDS. I THINK IT'S GREAT TO REALLY AS A SCIENTIST BE LEFT LARGELY TO YOUR OWN DEVICES AND LET FIELDS EVOLVE ORGANICALLY AND I DON'T MEAN TO SACRIFICE THAT BUT TO HAVE A HEAL-LIKE INITIATIVE, I THINK IT WILL BE AN IMPORTANT THING IN THE END TO PROVIDE SOME STRUCTURE ON TRANSLATION AND REALLY WELL-INFORMED CONVERSATIONS ABOUT WHAT MIGHT WORK OUT IN THE END AS WAS JUST MENTIONED. AT THE SAME TIME FOR THOSE INVOLVED IN CLINICAL WORK TO UNDERSTAND THE CHALLENGES AND HOW THEY MIGHT BECOME INVOLVED IN STEPS IN THE DEVELOPMENT AND TRANSLATION OF THE MOLECULES AND TARGETS WOULD BE HELPFUL. I APPRECIATE THE CONVERSATION. I LOOK FORWARD TO SIMILAR ONES HOPEFULLY NEXT YEAR I EXPECT ABOUT THIS TIME. >> NOW DR. KENNY? >> I'D LOVE TO SEE MORE BASIC SCIENTISTS BEING DRAWN IN TO TRANSLATIONAL WORK, PARTICULARLY IN THE ADDICTION FIELD. THERE'S VERY FEW LARGE COMPANIES FOCUSED ON ADDICTION AS AN ENDPOINT. AND IF WE DON'T BEGIN TO TACKLE IT, WHO WILL? THERE'S MANY FABULOUS TARGETS OUT THERE, MANY THINGS THAT WE COULD GO AFTER. I THINK THE RESOURCES AND EXPERTISE AVAILABLE AT NIH IS AVAILABLE, NIDA IS AMAZING, IF WE COULD DRAW MORE BASIC SCIENCE LABS IN THE AREA IT WOULD BE TO THE BENEFIT OF EVERYONE. MORE PANELS LIKE THIS WOULD HELP, EVANGELICALLIZING BUT CRITICAL IF WE BEGIN TO TACKLE THE EPIDEMIC. >> I TOO REALLY ENJOYED THE CONVERSATION HERE. I WISH WE HAD MORE CONVERSATIONS LIKE THIS IN THE COMING YEARS. I THINK IT'S REALLY HELPFUL FOR PRE-CLINICAL STUDY LIKE RESEARCHERS TO HAVE AN IDEA WHAT EXACTLY THE CLINICAL STUDY IS LOOKING FOR TOO SO THAT WE CAN SORT OF LIKE TRY TO BRIDGE THE TWO, TO MAKE A SMOOTHER TRANSITION. AND I THINK DOING A GOOD JOB COMING UP WITH MECHANISMS BUT I HOPE, REALLY HOPE THIS KIND OF CONVERSATION WILL COME ON A REGULAR BASIS. >> THANK YOU, DR. CAO. AND MARCO, MY CO-FACILITATOR HERE. >> YEAH, SURE. WELL, OBVIOUSLY LIKE THIS HAS BEEN GREAT. I ALWAYS THINK ABOUT BEFORE THERE WAS HEAL, WE HAVE THE COVID PANDEMIC, WE SAW THE LAST YEAR PUTTING TOGETHER ACADEMICS, INDUSTRY, BASIC AND TRANSLATIONAL SCIENCE TO GET THE VACCINE INTO PEOPLE. AND SO I THINK LIKE "HEAL" IS DOING SOMETHING SIMILAR, PEOPLE FROM THE BEST SCIENCE, PEOPLE INTERFACE WITH THE IND, WE ARE CLINICIANS, INDUSTRY PARTNERS, SO EVERYBODY LIKE KIND OF LIKE IS PUTTING EFFORT TOGETHER TO REACH THE SAME GOAL. I'M GRATEFUL THIS IS HAPPENING. SO THANK YOU. >> EXCELLENT. THANK YOU TO THE PANEL AND FOR ALL THE ATTENDEES FOR SUBMITTING EXCELLENT QUESTIONS. FEEL FREE TO FOLLOW UP WITH THE PANELISTS OR MYSELF AFTERWARDS IF YOU DIDN'T GET YOUR QUESTION ANSWERED, AND WE'RE ALL LOOKING FORWARD TO DR. COLLINS AND DR. BAKER'S NEXT SESSION, WHICH IS AT 4:30 P.M. THANK YOU FOR REALLY A GREAT SESSION. MORE THAN AN HOUR OF DISCUSSION, YOU GUYS DID AN EXCELLENT JOB. >> THANKS FOR YOUR HOSTING, MICHAEL. >> THANK YOU. >> THANKS. >> MICHAEL, THANK YOU. MARCO, THANK YOU, TERRIFIC SESSION. WE'RE GOING TO TAKE A QUICK STRETCH, AND AT 4:30 WE'LL RESUME. SO THANK YOU. >> WELCOME BACK, EVERYONE. THANK YOU FOR THOSE WHO HAVE REMAINED WITH US FOR THESE THREE DAYS. IT'S BEEN CHOCK FULL OF RESEARCH FINDINGS, AND ROBUST DISCUSSIONS, REALLY GREATLY APPRECIATE OUR LAST SESSION. WE'RE FOCUSED ON SOME OF THE NUANCES OF OUR BASIC RESEARCH PORTFOLIO THAT MAKES UP A BIG PART OF THE HEAL INITIATIVE. WE'VE COME TO THE END OF OUR FORMAL PRESENTATIONS, AND WE'D LIKE TO HAVE A FINAL SESSION WITH DR. REBECCA BAKER AND DR. FRANCIS COLLINS, AND SO WITH THAT I'M GOING TO TURN THINGS BACK OVER TO DR. BAKER TO TAKE% US THROUGH OUR FINAL WRAP-UP. DR. BAKER? >> THANK YOU, JACK. THANK YOU TO MICHAEL AND MARCO FOR A TERRIFIC DISCUSSION. I FEEL LIKE WE FINALLY CRACKED THE NUT OF HOW TO HAVE THESE DISCUSSIONAL SESSIONS AT THE END OF DAY 3. OH MY GOODNESS, IT'S BEEN SUCH A RICH SET OF PANELS AND DISCUSSIONS, AND I'M EXCITED TO BE ABLE TO SUMMARIZE IT FOR YOU HERE. HOPEFULLY WE CAN ADVANCE THE SLIDES AND YOU HAVE MY SLIDES. THANK YOU. SO, AS A REMINDER, THESE ARE THE QUESTIONS WE ASKED YOU BEFORE WE EVEN PLANNED THIS MEETING, WHAT ARE THE THINGS YOU WANT TO HEAR ABOUT FROM YOUR COLLEAGUES IN "HEAL." AND WHAT WOULD YOU LIKE TO BE THE FOCUS OF THIS YEAR'S SECOND ANNUAL HEAL INVESTIGATORS MEETING. YOU TOLD US THAT YOU WANT TO HEAR ABOUT HOW RESEARCH IS ADAPTING TO THE COVID-19 PANDEMIC AND THE NECESSARY CHANGES TO RESEARCH AND CARE ON ACCOUNT OF THE PANDEMIC. HOW WE CAN SUPPORT PATIENT ENGAGEMENT AND RESEARCH, HOW WE CAN LEARN BEST PRACTICES OF TREATING OUR PARTICIPANTS AS PARTNERS IN THE RESEARCH. WITH A RECOGNITION THAT HEALTH EQUITY IS AN URGENT GOAL FOR THE NIH, HOW CAN HEAL BE PART OF THE SOLUTION. STRENGTHENS PARTNERSHIPS IN RESEARCH AND WITH OUR FEDERAL COLLEAGUES YOU HEARD FROM EARLIER TODAY. AND THEN SHARING RESULTS, WITH ONE ANOTHER, WITH THE BROADER "HEAL" COMMUNITY, CLINICIANS, CARE GIVERS, PEOPLE WHO TURN DATA INTO IMPROVEMENTS FOR PATIENTS. NEXT SLIDE PLEASE. HERE'S WHAT WE HEARD ABOUT. WE HEARD ABOUT TERRIFIC RESILIENCE AND INGENUITY IN THE SCIENTIFIC COMMUNITY. I WAS IMPRESSED WITH APPROACHES WE LEARNED ABOUT, HOW RESEARCHERS WERE ABLE TO TURN ONE PLAN INTO A COMPLETELY DIFFERENT PLAN AND HAVE THE RESEARCH PARTICIPANTS REALLY LOVE IT AND THINK IT WAS BETTER THAN THE ORIGINAL. THE LANDSCAPE IS CHANGING. PEOPLE WITH SUBSTANCE USE DISORDERS ARE AT GREATER RISK FOR COVID. THEY ARE USING OTHER SUBSTANCES. WE ARE A COMMUNITY THAT'S BEEN ABLE TO PIVOT AND RESPOND TO EMERGING TRENDS. WE GOT -- KIND OF WENT -- [ NO AUDIO ] IN TREATING THEIR CARE. NEXT SLIDE PLEASE. YOU HEARD FROM DR. COLLINS AND U.S. SURGEON GENERAL VIVEK MURTHY ABOUT HOW EMOTIONAL WELL BEING CUTS ACROSS PAIN, SUBSTANCE USE, HOW THE COVID PANDEMIC HAS MADE THIS ESPECIALLY CHALLENGING, YET WE CAME TOGETHER AND ASKED QUESTIONS AND THOUGHT ABOUT HOW THE RESEARCH COULD BE ASSETS TO OUR INVESTIGATORS AND COMMUNITIES INCLUDING A FOCUS ON HOW CAN WE GIVE PROVIDERS THE RESOURCES THEY NEED TO PROVIDE ETCHED EAVED PRACTICES AND TREATMENTS TO THEIR PATIENTS. I LOVED THIS QUOTE, LOVE, COMPASSION AND KINDNESS ARE SOURCES OF STRENGTH, AND WE KNOW THIS BUT DON'T ALWAYS ACT ON IT. SO THIS IS JUST REDOUBLING OUR COMMITMENT TO ACT ON THAT KNOWLEDGE IN "HEAL." LASTLY, WE NEED YOUR VOICE AND EXPERTISE WE HAVE A TERRIFIC COLLECTION OF RESEARCHERS IN THE HEAL INITIATIVE AND YOU'RE COLLECTIVELY IN AN ASSET IN TELLING STORIES AND MAKING NEEDED CHANGES. NEXT SLIDE. WE HEARD ABOUT TRENDS AND PERSPECTIVES, HOW THE OPIOID CRISIS IS CHANGING DURING THE TIMES OF COVID, RISE OF SYNTHETIC OPIOIDS AND STIMULANTS. HOW THAT DRIVES US TO FOCUS ON SUSTAINABLE MODELS OF CARE THAT DON'T JUST FOCUS ON ONE DRUG OR ONE INTERVENTION BUT REALLY CAN TREAT THE WHOLE PERSON. WE HEARD ABOUT THE BALANCING ACT TREATING PAIN, KNOWING OPIOIDS ARE POWERFUL AND EFFECTIVE BUT CAN CARRY RISKS. AND HOW CHRONIC PAIN SITS IN THE WEB OF DISORDERS INCLUDING MENTAL HEALTH AND POTENTIALLY SUBSTANCE USE. AND HOW OUR ROLE AS A COMMUNITY IS TO PROVIDE THE NEEDED RESOURCES TO PRACTITIONERS TO GIVE THE BEST TREATMENTS TO THEIR PATIENTS. NEXT SLIDE PLEASE. WE'VE HEARD ABOUT THE HEAL DATA ECOSYSTEM, INFORMATION SHARING IS A CROSS-CUTTING THEME FOR "HEAL" OVERALL. BUT WE HEARD ABOUT A VISION FOR HOW AN INTEGRATED FAIR ECOSYSTEM TO DRIVE NEW INNOVATION IN TRANSLATION OF RESEARCH INTO PRACTICE WHILE ACCELERATING NEW DISCOVERIES. NEXT SLIDE PLEASE. AND THEN WE GOT INTO THE HARD STUFF, INTO THE SCIENCE THAT ALL OF YOU ARE WORKING ON IN YOUR INDIVIDUAL PROGRAMS AND PROJECTS. WE TALKED ABOUT THE DIFFERENT PAIN CONDITIONS THAT HEAL RESEARCH IS INTERROGATING AND COMING UP WITH ENHANCED KNOWLEDGE FOR TREATMENT. AND THAT INCLUDES PAIN MANAGEMENT AMONG ADOLESCENTS, FOLLOWING CASAREAN, CHRONIC LOW BACK PAIN AND WHEN THE PATIENT IS AT RISK WHEN OPIOIDS MIGHT BE REDESCRIBED. LINKAGE IS ESSENTIAL, WE TALKED ABOUT MODELS AND HOW RESEARCH CAN TEST THEM AND PROVIDE A ROAD TOWARDS SUSTAINABILITY AS THEY GET INTEGRATED AND THAT INCLUDES THE ROLE OF NURSE CARE MANAGERS, LEVERAGING ELECTRONIC HEALTH RECORDS, INNOVATIVE WAYS OF FOLLOWING UP, ENGAGEMENT THROUGH TELEMEDICINE, POSTERS AND MEDIA DESCRIBED WAYS TO EXPAND ACCESSIBILITY NOT JUST FOR RECRUITMENT EFFORTS BUT BUILDING STRONGER COMMITMENTS WITH RESEARCH COMMITMENTS, BASED ON THE NEEDS OF THE INDIVIDUAL STUDY AND WHERE IT'S CARRIED OUT AND AMONG THE PATIENT POPULATION THAT WE'LL STUDY. NEXT SLIDE PLEASE. ON SECOND DAY OF THE MEETING WE MOVED INTO TERRIFIC DISCUSSION ABOUT ENGAGING COMMUNITIES IN RESEARCH, LED BY DR. KOROSHETZ. WE HEARD FROM REAL LEADERS IN THIS AREA ABOUT WHAT CAN BE ACCOMPLISHED WHEN COMMUNITY ENGAGEMENT IS TAKEN SERIOUSLY AND INCORPORATED IN ALL PARTS OF A RESEARCH STUDY. AND HOW THESE INTENTIONAL CONNECTIONS BETWEEN THE RESEARCHERS PROVIDERS AND NON-JUST A FEW RESEARCH PARTICIPANTS BUT COMMUNITY ORGANIZATIONS THAT SURROUND THEM AND ARE GOING TO HAVE SUSTAINABLE CONNECTIONS WITH THEM HELPS BUILD TRUST WE NEED TO CARRY OUT OUR RESEARCH. AND IT'S GOING TO DEPEND ON THE COMMUNITY, IT'S NOT THE SAME EVERYWHERE. SUCCESS IS NOT THE SAME EVERYWHERE. AND SO WE HAVE TO BE READY TO BE ADAPTABLE AND TARGET OUR EFFORTS TO DIFFERENT INDIVIDUALS AND DIFFERENT COMMUNITIES IN NEED. AND THEN LASTLY SUSTAINABILITY IS ALWAYS AN ISSUE, ESPECIALLY AN ISSUE HERE. WE RELY ON THESE GRASS ROOTS GROUPS AND THEIR CONNECTIONS WITH INDIVIDUALS BUT WE ALSO NEED TO FIND WAYS THAT ONCE SOMETHING IS FOUND TO BE EFFECTIVE WE KEEP DOING IT AND DON'T KIND OF LET THAT PROJECT RUN OUT AND START ANEW, AND THEN ALSO INCLUDES SUSTAINED CONNECTIONS WITH THE INDIVIDUALS IN THOSE COMMUNITIES AND IN THOSE STUDIES. THE STUDY ENDS, STAYING CONNECTED FOR DISSEMINATION AND THE NEXT OPPORTUNITY ARE JUST AS IMPORTANT AS THE FIRST GO AROUND. SO NEXT SLIDE PLEASE. IN THE ADVANCING HEALTH EQUITIES SECTION WE STARTED WITH SOME SOBERING STATISTICS ABOUT JUST HOW THE OPIOID CRISIS AND UNDERTREATMENT OF PAIN ARE, ESPECIALLY DAMAGING AND PROBLEMATIC IN COMMUNITIES OF COLOR, UNFORTUNATELY WE DON'T HAVE ALL THE DATA WE NEED TO REALLY KNOW WHAT'S GOING ON BUT WE SEE VERY PROBLEMATIC TRENDS. THERE WAS ASSUMPTION IT WAS TRUE IN WHITE RURAL COMMUNITIES, NOT TRUE, CURRENT TRENDS ESCALATE WE NEED TO BE ESPECIALLY FOCUSED ON HOW "HEAL" CAN BE PART OF THE SOLUTION, PART OF ADDRESSING HEALTH EQUITY THROUGH RESEARCH. THERE ARE FORTUNATELY A LOT OF USEFUL TOOLS WE CAN TAKE UP IN THIS EFFORT AND THAT INCLUDES PRINCIPLES OF COMMUNITY-BASED PARTICIPATORY RESEARCH, OPPORTUNITIES FOR LEVERAGING NEW DATA SOURCES, AND THE PEOPLE INTEGRATING PEOPLE LIVED EXPERIENCE AND NOT JUST LIVED EXPERIENCE IN A PAIN CONDITION OR SUBSTANCE USE BUT SPECIFIC SETTINGS, INCARCERATED NOT JUST AS PARTICIPANTS BUT IN THE GOVERNANCE AND CONDUCT AND COMMUNICATION AROUND THE STUDY. AND THAT WAS ANOTHER TERRIFIC PANEL DISCUSSION. NEXT SLIDE PLEASE. WE THEN BROKE UP AND HAD A BUNCH OF FOCUSED AND REALLY DYNAMIC DISCUSSIONS ON SPECIFIC ISSUES IN HEAL RESEARCH. AS YOU ALL KNOW, DATA THAT WE COLLECT IS OFTEN HIGHLY SENSITIVE AND CAN REALLY GET IN THE WAY OF SOMEONE'S LIFE IF IT GETS MISCOMMUNICATED OR MISINTERPRETED. AND SO STUDIES NEED TO CONSIDER HOW THE WAY THEY COLLECT DATA RELATED TO SUBSTANCE USE CAN PREVENT MANDATORY REPORTING REQUIREMENT, UNINTENDED CONSEQUENCES, AND WE NEED TO CONTINUE TO RESEARCH THAT. COMMUNITY ADVISORY BOARDS WE KNOW THEY ARE REALLY HELPFUL BUT WE CAN STRENGTHEN OUR EFFORTS IN INCLUDING THEM AND ALSO IN OUR WORK FORCE BUILDING A WORKFORCE THAT MATCHES THE POPULATIONS WE SEARCH AND BUILDING MEANINGFUL ENGAGEMENT THAT WAY. AND THEN ALSO RECOGNIZING THE CURRENT LANDSCAPE, ADOPTING INTERVENTIONS TO REMOTE DELIVERY, IT'S GOING TO STAY THAT WAY, WE NEED TO KNOW WHAT WORKS AND UNDERSTAND HOW DISPARITIES AND ACCESS PLAY INTO ACCESSIBILITY OF THESE NEW INTERVENTIONS AND IN THE VIRTUAL ERA. NEXT SLIDE PLEASE. YOU ARE HEARD IN THE LAST SESSION, WE LIKE TO ISOLATE THINGS AND POSE RAZOR SHARP QUESTIONS BUT OUR PATIENTS DON'T LOOK LIKE THAT. COMORBIDITIES POSE BARRIERS, WE HAVE TO INCORPORATE INTO THE STUDY BOTH AT THE BEGINNING AND END AND IN BETWEEN AND POLY SUBSTANCE USE IS A REALITY, WE HAVE EVIDENCE FOR MANAGEMENT, DESPERATELY NEED MEDICATIONS THAT TREAT STIMULANT USE DISORDER, HELPFUL IN POPULATIONS AND INDIVIDUALS WHO USE MORE THAN ONE SUBSTANCE, SO WE'LL CONTINUE WORKING WITH THE FDA TO DEFINE THAT AREA. AND THEN DISSEMINATION, WE TEND TO BE THE CHORUS, WE'RE CAREFUL ABOUT THE LANGUAGE BUT THERE ARE OPPORTUNITIES TO BE PROMISING PRACTICES IN THAT AREA AND USE OUR RESOURCES AND MATERIALS WE'VE CREATED TO CORRECT NEGATIVE OR STIGMATIZING IMAGES THAT HAVE THESE DEADLY AND DEVASTATING CONSEQUENCES. NEXT SLIDE PLEASE. THIS MORNING WE STARTED WITH A TERRIFIC SET OF PRESENTATIONS. I WAS JUST ENTHRALLED HEARING ABOUT THE WAYS THAT POSITIVE CHANGES IN HEALTH CARE AMID THE PANDEMIC HAVE REALLY EMPOWERED COMMUNITY AND RESEARCHERS AND CONNECTIONS WITH ONE ANOTHER. SO VIRTUAL DELIVERY HAS INCREASED THE REACH OF CERTAIN EVIDENCE-BASED INTERVENTIONS, IT'S LOWERED REGULATORY BARRIERS AND SOME PAYMENT BARRIERS. THERE ARE SIGNS THAT ONLINE RECRUITMENT AND ENGAGEMENT ARE NOT JUST KIND OF A FLASH IN THE PAN BUT ARE GOING TO STAY AND BE EFFECTIVE IN PEOPLE THAT WE'RE RECRUITING INTO STUDIES LIKE THESE AND CAN EVEN HELP WITH SOME OF THE TEAM-BASED PROGRESS AND WAYS THAT WE ESTABLISH INTERDISCIPLINARY CONNECTIONS BUT NEED TO BE CAREFUL. WE KNOW PEOPLE DON'T ALWAYS HAVE INTERNET CONNECTIONS, MINUTES ON THEIR CELL PHONES, AND THERE MAY BE CHEAP AND EASY WAYS TO PROVIDE OUR PARTICIPANTS AND TAKE AWAY SOME BURDEN OF THESE NEW VIRTUAL INTERVENTIONS WHILE ALSO MEETING CULTURAL AND COMPLEX NEEDS. WE THEN CONNECTED WITH OUR FEDERAL PARTNERS, YOU CAN SEE DR. TABAK LED THE PANEL DISCUSSION. WE KNOW NEXT YEAR IS GOING TO BE THE HIGHEST NUMBER OF DRUG OVERDOSE DEATHS EVER, SO COLLABORATION AND COORDINATION IS NEEDED NOW MORE THAN EVER. THE DEPARTMENT OF HEALTH AND HUMAN SERVICE AND AGENCIES WITHIN RELY ON YOU ALL, ON THE HEAL RESEARCHERS, TO DEVELOP EVIDENCE TO INFORM PRACTICE. AND WE NEED MORE RESEARCH IN THE AREAS OF POLYSUBSTANCE USE, IN RECOVERY SERVICES, IN UNDERSTANDING HOW TO TREAT SUBSTANCE USE DISORDERS IN PRIMARY CARE AND IN SPECIFIC PAIN CONDITIONS MAKING GUIDELINES STRONGER IN PRACTICE, MORE EVIDENCE-BASED. AND WE MOVED INTO OUR LAST SESSION WHICH WAS HIGHLY INTERACTIVE AND REALLY FRUITFUL. CONNECTING THE PRE-CLINICAL TO THE TRANSLATIONAL IN UNDERSTANDING NEW EFFECTIVE USER FRIENDLY TREATMENTS FOR BOTH PAIN AND OPIOID USE DISORDER, A NUMBER OF DIFFERENT CONDITIONS UNDER INVESTIGATION BUT A LOT OF COMMONALITIES IN WHAT'S NEEDED IN THOSE RESEARCH STUDIES AND THAT INCLUDES PREDICTIVE MODELS, NOT JUST ONE ANIMAL BUT THINGS THAT ARE GOING TO NARROW THAT GAP FROM BENCH TO BEDSIDE BIOMARKERS, OPPORTUNITIES FOR TRANSLATION, FINDINGS THAT DO COME THROUGH TO SAVE TIME NEXT GO ROUND AND FDA REGULATORY PROCESS, SO GRATIFIED TO HEAR HOW OUR COLLEAGUES ACROSS NIH ARE REALLY EDUCATED RESOURCES. I KNEW THIS, THOSE OF YOU WHO WORK WITH THEM KNOW THIS, BUT IT'S A TERRIFIC RESOURCE TO INVESTIGATORS. PLEASE GET IN TOUCH WITH THEM, AS YOUR CITIES MOVE TOWARDS THAT PHASE BECAUSE THEY BRING A WEALTH OF EXPERIENCE AND CAN BE REALLY HELPFUL IN NAVIGATING THIS PROCESS AND WE REALLY NEED IT. NEXT SLIDE PLEASE. THIS WAS A THREE-DAY VIRTUAL MEETING. IT'S SAD NOT TO BE TOGETHER. WE HAVE OTHER VIRTUAL WAYS THAT WE HOPE TO CONTINUE TO CONNECT INCLUDING THE HEAL IDEA SCALE PLATFORM BUT, NEXT SLIDE PLEASE, WE HAVE A NUMBER OF OPPORTUNITIES OUT THERE THAT I HOPE YOU CHECK OUT, THAT SEEK TO ENHANCE DIVERSITY OF WORK FORCE IN TERMS OF AGE, RACE AND ETHNICITY, AND THOSE WILL CONTINUE TO BE OUT. IF YOU'RE LOOKING TO STRENGTHEN YOUR TEAM THIS WAY PLEASE TAKE A LOOK AT THESE OPPORTUNITIES. AS WELL AS, NEXT SLIDE PLEASE, ONGOING MEDICATION DEVELOPMENT OPPORTUNITIES RELEVANT TO THE DISCUSSION WE JUST HAD. ONE MORE SLIDE. THANK YOU. THIS IS ALL ON OUR WEBSITE WHICH WILL CONTINUE TO BE UPDATED AS MORE OPPORTUNITIES COME WE TRANSLATE ALL OF THIS DISCUSSION INTO NEW IDEAS AND NEW VEHICLES FOR RESEARCH. SO NEXT SLIDE PLEASE. THIS IS MY FAVORITE PART WHERE I SAY THANK YOU TO EVERYONE WHO TOOK PART IN PLANNING THIS MEETING. THIS WAS NOT LIKE THE FIRST MEETING WHERE WE WERE ALL GETTING ON THE SAME PAGE. WE HAD ACTIVE AND CREATIVE CONNECTIONS WITH THE INVESTIGATORS, ALL OF YOU, PLANNING THE MEETING. NEXT SLIDE PLEASE. THE P.I.s ON THE P.I. PLANNING TEAM GAVE US TERRIFIC ADVICE, AND YOU CAN SEE FROM HOW WELL THE MEETING WENT HOW WELL THEY THOUGHT THROUGH WHAT WAS GOING TO BE ENGAGING AND INTERESTING. THANK YOU. NEXT SLIDE PLEASE. THE NIH STAFF, ON THE PLANNING TEAM, THANK YOU TO THE WHOLE GROUP OF STAFF. THESE ARE YOUR PROGRAM OFFICERS AND LEADS OF THE DIFFERENT "HEAL" PROGRAMS. THERE ARE A LOT OF PEOPLE WHO HELPED IN THIS REGARD. THANK YOU. NEXT SLIDE PLEASE. HERE ARE ALL OF THEIR NAMES. NEXT SLIDE PLEASE. AND OF COURSE THE MEETING CO-CHAIRS, A SMALL AND MIGHTY TEAM, LINDA PORTER AND JACK STEIN. ERIN, THANK YOU, IN THE OFFICE OF THE DIRECTOR. IF YOU GAVE A PRESENTATION, YOU INTERACTED WITH HER. THANK YOU, ERIN. NEXT SLIDE PLEASE. AND THANK YOU TO THE HEAL EXECUTIVE COMMITTEES, NIH DIRECTORS WHO OVERSEE ALL OF "HEAL" AND MANY OF THEM WERE ABLE TO MODERATE AND TAKE PART IN THE DISCUSSIONS OVER THE PAST THREE DAYS. SO NEXT SLIDE PLEASE. HERE IS DR. COLLINS AGAIN WHO IS ABLE TO JOIN US. DR. COLLINS, WOULD YOU LIKE TO SAY ANYTHING TO THE GROUP NOW THAT WE ARE RECONVENED? >> I WOULD VERY MUCH LIKE TO SAY SOMETHING TO THE GROUP, ALTHOUGH THE PICTURE MAY SUGGEST THERE'S SOMETHING COMING. HOLD ON A MOMENT BEFORE YOU START THAT ONE UP. YOU WERE THANKING ALL SORTS OF PEOPLE, I NEED TO ADD A THANK YOU TO YOU, DR. BAKER, AS OUR DIRECTOR OF THE HEAL INITIATIVE FOR NIH FOR ALL THE AMAZINGLY CREATIVE WAYS THAT YOU STEERED THIS ENTERPRISE AND PUT THIS REMARKABLE MEETING TOGETHER WITH LOTS OF HELP, AS YOU SAID, BUT THEM DEPENDING ON YOU AND YOUR WISE VISION TO CARRY THIS FORWARD. I'VE BEEN ABLE TO SAMPLE A LITTLE BIT OF WHAT WAS HAPPENING. NIH DIRECTOR'S LIFE RIGHT NOW IS PARTICULARLY INTENSE, TALKING TO YOU TODAY FROM MY HOME OFFICE, I SPOKE TO YOU FROM NIH TWO DAYS AGO. IN BETWEEN, I THINK I'VE DONE ABOUT AT LEAST A DOZEN PRESS INTERVIEWS, ALL ARE FOCUSED ON VACCINE HESITANCY AND TRYING TO CONVINCE VARIOUS GROUPS STILL ON THE FENCE THAT THIS IS SOMETHING THAT THEY DON'T WANT TO MISS OUT ON. SO I'VE TALKED TO SOME CHAMPION OF WRESTLEMANIA, TALKED TO MANY PEOPLE WHO ARE LEADERS IN THEIR COMMUNITIES, IN THEIR CHURCHES, TO TRYING TO GET THAT WORD OUT. THAT DISTRACTED ME FROM BEING ABLE TO SOAK UP A LOT OF THE GREAT SCIENCE THAT YOU ALL DISCUSSED BUT I'M GLAD THAT I GOT TO HEAR DR. BAKERS'S SUMMARY AND WHAT HAPPENED IN EACH OF THESE REMARKABLE SESSIONS. I SEE THERE'S STILL 159 OF YOU THAT HAVE MANAGED TO STICK WITH IT. THAT'S A TESTIMONY TO THE FACT THAT THIS MEETING MUST HAVE BEEN PRETTY DARN GOOD, AFTER THREE DAYS OF ZOOMING THAT CAN TEND TO CAUSE A LITTLE ATTRITION. YOU HAVE 160, HAVE MANAGED TO STICK WITH IT. I THINK THAT'S BECAUSE YOU REALLY CARE ABOUT THIS. YOU REALLY WANT THIS TO BE SOMETHING THAT YOU CAN CONTRIBUTE TO. YES, I KNOW MORE OF YOU ON THE VIDEOCAST AS WELL, SO I'M UNDERESTIMATING BY SIGNIFICANT NUMBERS THOSE WHO ARE WATCHING RIGHT NOW. THINKING ABOUT WHERE WE ARE RIGHT NOW, THINKING ABOUT THIS IN THE COURSE OF THIS WHOLE MEETING, IT REALLY IS RATHER STUNNING THAT THIS INITIATIVE, "HEAL," FINDS ITSELF RIGHT IN THE NEXUS OF WHAT I WOULD SAY ARE THE THREE MOST CHALLENGING PUBLIC HEALTH CRISES OF OUR ERA. ONE OF THEM OF COURSE IS THE EPIDEMIC OF OPIOID USE DISORDER AND OPIOID OVERDOSE DEATHS ASSOCIATED WITH THE PROBLEM OF CHRONIC PAIN AND NEED TO FIND BETTER ANSWERS TO THAT. BUT THEN THAT INTERSECTS WITH THE COVID-19 CRISIS, AS WE'VE TALKED ABOUT EXTENSIVELY IN THE COURSE OF THIS MEETING. BUT IT ALSO INTERSECTS WITH THIS OTHER CRISIS WHICH HAS BECOME PARTICULARLY OBVIOUS ALTHOUGH% IT'S BEEN THERE ALL ALONG, IN THE COURSE OF THE LAST YEAR WITH THE MURDER OF GEORGE FLOYD, RECOGNITION THAT OUR SOCIETY IS STILL VERY MUCH CARRYING THE BAGGAGE OF 400 YEARS OF THE AFTERMATH OF SLAVERY, AND THAT WE DO HAVE THIS ISSUE OF STRUCTURAL RACISM THAT IS PRETTY MUCH WRITTEN INTO ALL OF OUR INSTITUTIONS, ALL THE WAYS IN WHICH OUR HEALTH CARE IS DELIVERED. SO WE HAVE A HEALTH EQUITY PROBLEM. I'M REALLY GLAD YOU LOOKED CLOSELY AT THAT IN THE COURSE OF THIS MEETING AND FROM WHAT DR. BAKER JUST SAID IT SOUNDS AS IF THERE HAVE BEEN SOME ADDITIONAL REVELATIONS THERE AS WELL. FOR THOSE INDIVIDUALS WHO ALREADY SUFFERED AN UNDUE BURDEN OF HEALTH DISPARTIES AND NOW SUFFERING UNDUE BURDEN FROM COVID, IT'S CLEAR THAT THE EPIDEMIC OF SUBSTANCE USE DISORDER IS ON THAT LIST AS WELL. SO YOU GOT TO BE REAL PIONEERS TO JUMP INTO THIS SPACE WHERE YOU HAVE THESE THREE MAJOR PUBLIC HEALTH CRISES ALL COMING TOGETHER IN A WAY THAT IS CREATING TERRIBLE TRAGEDY, LOSS OF LIFE, CERTAINLY ENORMOUS STRESS ON HUMAN EXPERIENCE. AND YET WE ARE THE RIGHT TEAM AT THE RIGHT TIME, FEARLESSLY ROLLING UP YOUR SLEEVES DEMONSTRATING YOU CAN TAKE THIS ON. I'M GLAD DR. BAKER MENTIONED IN TERMS OF THE HEALTH EQUITY ISSUES SOMETHING WE NEED TO FOCUS ON IS OUR OWN WORKFORCE, TO MAKE SURE WE HAVE THE DIVERSITY IN THE HEAL INITIATIVE INVESTIGATORS TO WELL REFLECT THE CONCERNS THAT WE MUST NOW PAY ATTENTION TO IN TERMS OF DIVERSITY OF THE NEEDS OUT THERE. I'M GOING TO PERSONALLY BE VERY MUCH EXCITED TO SEE THAT GO FORWARD. SO YOU'VE HAD TO SHOW IN A WAY I DON'T THINK ANY OF US SAW COMING WE WE HAD OUR FIRST MEETING 16 MONTHS AGO, THE KIND OF FLEXIBILITY AND CREATIVITY, KIND OF ABILITY TO WORK ACROSS DISCIPLINES, YOU HAD TO BUILD ON THINGS WE ALREADY KNEW BUT NOT BE LIMITED. LOOK WHAT YOU'VE DONE WITH THE ADVENT OF TELEMEDICINE TO TURN COVID, SUCH A DARK EXPERIENCE IN SO MANY OTHER WAYS, INTO SOMETHING THAT WAS REALLY PROFOUNDLY BENEFICIAL AND CAN NOW CONTINUE TO BE. YOU HAVE TO BE BOLD. WE'VE TRIED TO BE AS MUCH AS WE CANNOT LIKE, YOU KNOW, THOSE DUSTY OLD BUREAUCRATS WHO DON'T WANT YOU TO DO OTHER THAN WHAT IT SAID IN THE PAPER. WE WANT YOU TO REALLY BE READY TO CHALLENGE US WITH NEW IDEAS, NEW APPROACHES, AND WE WANT TO BE YOUR PARTNERS. THE VERY END OF DR. BAKER'S PRESENTATION, YOU SAW A LIST OF GRANT OPPORTUNITIES, YOU HOPE YOU LOOK AND THINK ABOUT THOSE, THERE MAY BE MORE TO COME. WE DON'T KNOW. NEXT WEEK I'LL BE A WITNESS IN FRONT OF THE HOUSE AND SENATE APPROPRIATIONS COMMITTEES, TRYING TO FIGURE OUT WHAT TO DO WITH THE NIH BUDGET FOR FISCAL YEAR 22, WHICH WILL BEGIN THEORETICALLY IN OCTOBER, PROBABLY MORE LIKE DECEMBER. IT WILL BE VERY INTERESTING TO SEE WHAT HAPPENS BECAUSE I KNOW THOSE MEMBERS OF CONGRESS ARE DEEPLY CONCERNED ABOUT THE CRISIS OF SUBSTANCE USE DISORDER AND PAIN AND ARE LIKELY TO BE ASKING YOU A LOT OF QUESTIONS. THINK OF ME NEXT TUESDAY, WEDNESDAY, AS I'M GETTING GRILLED ABOUT WHAT WE'VE DONE. I'M GOING TO COME TO THOSE HEARINGS WITH A GREAT DEAL OF CONFIDENCE THAT I CAN REPORT ON WHAT THE HEAL INITIATIVE HAS DONE IN A WAY THAT THEY SHOULD BE INSPIRED BY BECAUSE I'M INSPIRED BY THAT. SO YOU'VE HEARD A LOT OF WORDS, PROBABLY YOU'RE PROBABLY ABOUT AT THE POINT OF SAYING THAT'S ABOUT ENOUGH WORDS. BEFORE WE GO THOUGH I DO REMEMBER VERY FONDLY WHEN WE MET FOR THE FIRST TIME IN JANUARY OF 2020, IT WAS A SPONTANEOUS IDEA AT THE LAST MINUTE BUT MAYBE THIS GROUP THAT CAME TOGETHER FOR THE FIRST TIME GETTING TO KNOW EACH OTHER, DEVELOPING RELATIONSHIPS AND COLLABORATIONS, IT WAS BECOMING LIKE A FAMILY. FOR ME, WHAT A FAMILY DOES WHEN YOU KIND OF COME TO THE PLACE OF CLOSING UP AN EXPERIENCE, YOU SHOULD SING TOGETHER. BACK IN, BEFORE ZOOM, I GOT YOU ALL TO SING A SONG CALLED "IF NOT NOW, TELL ME WHEN." BECAUSE IT SEEMED LIKE A GOOD KIND OF IDEA FOR A PROJECT THAT WAS GETTING STARTED AT A TIME OF GREAT NEED. THAT'S CERTAINLY BEEN THE CASE FOR THESE LAST 16 MONTHS. IT DOESN'T WORK TO DO GROUP SINGING BY ZOOM. I DON'T KNOW IF YOU'VE EVER TRIED TO SING HAPPY BIRTHDAY TO SOMEBODY WHEN YOU HAD 20 PEOPLE ON A ZOOM CALL. IT'S ABOUT AS PAINFUL AS ANYTHING I'VE EVER HEARD IN MUSIC. YOU'RE OFF THE HOOK. I'M NOT GOING TO EXPECT A GROUP PARTICIPATION THIS TIME. ZOOM INCIDENT EVEN GREAT FOR LIVE PERFORMANCE OF VOICE AND GUITAR WHICH IS WHAT REBECCA THOUGHT MAYBE I COULD PRODUCE. INSTEAD, WITHIN THE LAST 24 HOURS, A SONG EMERGED. MY WIFE DIANE RECORDED IT ON HER iPHONE, IT WILL APPEAR HERE IN A MOMENT. THIS TIME IT'S A DIFFERENT SONG. BUT IT'S A SONG THAT'S A BIT MORE THINKING OPTIMISTICALLY ABOUT GETTING THROUGH THIS COVID CHALLENGE INTO A NEW PLACE, PAST THE PANDEMIC, THEN WHAT, SOMEWHERE, SOUNDS LIKE MAYBE A SONG IN THERE SOMEWHERE. PAST THE PANDEMIC. WELL, MAYBE WE'LL SAY A BRIEF WORD OF FAREWELL. ERIN, IF YOU HAVE THE CONTROLS, ROLL THAT SONG. * * SOMEWHERE PAST THE PANDEMIC, WHEN WE'RE FREE * THERE'S A LIFE I REMEMBER FULL OF ACTIVITY * SOMEWHERE PAST THE PANDEMIC * NO MORE QUARANTINE * WE'LL ALL STAY WELL AND HEALTHY * THANKS TO THOSE SAFE VACCINES * SOMEDAY WITH ALL THE "HEAL" P.I.s, WE'LL MEET TOGETHER AND DEVICE NEW WAYS FOR REVEALING * CURES FOR OPIOIDS AND PAIN, CURES FOR PATHWAYS IN THE BRAIN THAT POINT TOWARDS HEALING * SOMEWHERE PAST THE PANDEMIC * LIFE WILL RESUME * WE'LL ALL COMPLAIN ABOUT THE TRAFFIC * FORGETTING HOW WE LIVED ON ZOOM * SOMEWHERE PAST THE PANDEMIC * I'LL HUG MY FRIENDS * AND THANK ALL THE HEROES AROUND * THAT BROUGHT THE PANDEMIC'S END * WITH MANY THANKS TO ALL OF YOU * THE WORLD IS WAITING * ONWARD GO TEAM "HEAL" GO TEAM HEAL! >> WELL, OKAY. THAT WAS A ONE-TIME THING. YOU HEARD THE ONE AND ONLY RENDITION OF THAT PARTICULAR SOMEWHERE PAST THE PANDEMIC. WE ALL DREAM OF GETTING TO THAT PLACE, AND WE'RE ON THE WAY. WITH YOUR HELP, WE'LL MAKE THE MOST OF THAT TOO. JUST AS YOU HAVE MADE THE MOST OF THIS INCREDIBLY CHALLENGING TIME. SO, YEAH, AS I SAID IN THOSE LAST THREE WORDS, GO TEAM HEAL, GO! WE'RE COUNTING ON YOU. YOU'VE DONE AMAZING THINGS ALREADY, I KNOW THERE'S MUCH MORE TO COME. BACK TO YOU, REBECCA. >> THANK YOU, EVERYONE. THANK YOU, DR. COLLINS, FOR A BEAUTIFUL SONG. NEXT YEAR WE WILL BE TOGETHER, I KNOW, AND THANK YOU TO ALL OF THE PARTICIPANTS AND ORGANIZERS. SEE YOU NEXT YEAR.