WELCOME TO THE FIRST MEETING OF THE "HEAL," HELPING TO END ADDICTION LONG-TERM INITIATIVE MULTI-DISCIPLINARY WORKING GROUP, I'M REBECCA BAKER, WHO HAS BEEN SENDING YOU E-MAILS AND REQUESTS FOR INFORMATION AND DOCUMENTS, AND WANTED TO START BY SAYING THANK YOU VERY MUCH FOR VOLUNTEERING FOR SERVICE ON THIS REALLY IMPORTANT WORKING GROUP. YOU'LL HEAR MORE TODAY FROM OUR DIFFERENT INSTITUTE AND CENTER DIRECTORS AND NIH LEADERS ABOUT WHAT THE INITIATIVE IS, BUT SUFFICE IT TO SAY IT'S VERY AMBITIOUS, WE'RE MOVING FAST, AND WE NEED YOUR HELP IN CRAFTING AND GUIDING THE BEST PORTFOLIO OF RESEARCH PROGRAMS IN "HEAL." SO I WILL BE THE DESIGNATED FEDERAL OFFICIAL FOR THIS PANEL, MEANING IF YOU HAVE QUESTIONS ABOUT POTENTIAL CONFLICTS OR THE AGENDA, OR OTHER ISSUES RELATED TO THE FUNCTION OF THE WORKING GROUP PLEASE FEEL FREE TO CONTACT ME AT ANY TIME, EVEN DURING THE MEETING, YOU CAN COME OVER AND ASK ME A QUESTION. WE WILL MEET TODAY FOR THE DURATION, TALKING ABOUT "HEAL" IN THE BROADEST TERMS, PRESENTING A SELECTION, IT'S JUST A SELECTION OF THE RESEARCH PROGRAMS THAT THE INITIATIVE INCLUDES. WE HAVE QUITE A FEW, AS YOU'LL HEAR, AND WHAT WE'RE TRYING TO DO WITH THIS WORKING GROUP IS TO SELECT A SUBSET OF THE PROJECTS WITHIN THE INITIATIVE, WHERE THE INPUT AND GUIDANCE FROM YOU ALL WILL BE ESPECIALLY VALUABLE IN HELPING US CRAFT THE INITIATIVE AND SELECT THE BEST OVERALL DISTRIBUTION OF PROGRAMS TO INCLUDE. SO, TODAY YOU'LL HEAR ABOUT SOME OF THEM. THERE ARE ALSO SOME MATERIALS IN YOUR FOLDERS THAT REPRESENT THE FULL LIST OF FUNDING OPPORTUNITY ANNOUNCEMENTS THAT HAVE COME OUT THROUGH "HEAL," AND THEN DOCTORS COLLINS, VOLKOV AND KOROSHETZ WILL GO THROUGH THE INITIATIVE AT A HIGH LEVEL AND PRESENT YOU TO AN OVERVIEW. THEN, AFTER THAT WE'LL GET INTO SOME OF THE SPECIFICS OF THE PROGRAMS WITH THE SCIENTIFIC EXPERTS AT NIH LEADING SOME PROGRAMS WITHIN "HEAL." SO, WE WILL HAVE LOTS OF TIME FOR DISCUSSION AND QUESTIONS, SO PLEASE DO NOT HESITATE TO PUT YOUR VOICE BOX ON AND ASK A QUESTION OF ANY OF US. BUT WE'RE LOOKING FORWARD TO A REALLY PRODUCTIVE GROUP AND THANK YOU VERY MUCH FOR JOINING ON. NOW, I KNOW THAT LAST WEEK WE HELD A CONFLICT OF INTEREST TRAINING SESSION BY WEBEX, AND THANK YOU FOR THOSE WHO WERE ABLE TO JOIN. WE ALSO ARE FORTUNATE TO HAVE HERE TODAY DR. TABAK, OUR DEPUTY -- PRINCIPAL DEPUTY DIRECTOR AND ETHICS COUNSELOR HERE AT NIH TO GO THROUGH SOME OF THE PARTICULARS TO REMIND YOU OF WHAT WE DISCUSSED. AND THEN AFTER THAT WE'LL HAVE A CHANCE TO GO THROUGH THE GROUP AND ALL INTRODUCE OURSELVES AND TALK ABOUT EXPERTISE AND BACKGROUNDS THAT WILL HELP US INFORM THE HEAL INITIATIVE AND THIS WORKING GROUP. I'LL HAND IT OVER TO DR. TABAK. >> GOOD MORNING, EVERYBODY. I'D LIKE TO ADD MY WELCOME AND THANKS TO EACH OF YOU. AND I DO APPRECIATE THE FACT THAT MANY OF YOU DID PARTICIPATE IN THE WEBINAR LAST WEEK. BUT FOR THOSE WHO DIDN'T AND JUST AS A REFRESHER, FOR THOSE WHO DID, MANY OF YOU HAVE SERVED ON NIH STUDY SECTIONS AND NIH COUNCILS, AND SO THESE ARE FAMILIAR THINGS TO YOU. BUT THIS IS A WORKING GROUP. IT IS NEITHER A STUDY SECTION NOR COUNCIL. AND SO IT'S HELPFUL, I THINK, TO JUST GO THROUGH THE PRINCIPLES. SO, PEOPLE ARE ALWAYS ASKING ME AS A DEPUTY ETHICS COUNSELOR FOR THE AGENCY, WELL, HOW DO YOU DECIDE WHO SHOULD BE IN THE ROOM, AND WHO SHOULDN'T BE IN THE ROOM, AND, YOU KNOW, EXPERTS, NON-EXPERTS. OKAY. SO THERE'S A FUNDAMENTAL PRINCIPLE OF ETHICS FOR THE -- WITH COMMON SENSE. THAT MAY SOUND OXYMORONIC TO SOME OF YOU, BUT ETHICS, COMMON SENSE, TO JUST REMEMBER THIS PRINCIPLE. WITHOUT TENSION, THERE CAN BE NO MUSIC. SO, I COULD MAKE THIS A CONFLICT-FREE ENVIRONMENT, AND THERE WOULD NOT BE A SINGLE EXPERT IN THE ROOM. ALL THAT WOULD BE LEFT IS ME, OKAY? I COULD TALK TO MYSELF, BUT -- BECAUSE I'M THE ONLY ONE WHO LIST TONS ME, SO THAT WOULDN'T WORK EITHER. SO-- BUT ALL KIDDING ASIDE, THE GOAL HERE IS TO IDENTIFY POTENTIAL CONFLICTS, REAL OR PERCEIVED, AND TO MANAGE THEM. AND WITH ALL OF YOUR HELP, THAT'S EXACTLY WHAT WE'RE GOING TO DO, SO THAT THE AGENCY CAN HEAR COMMENTS FROM YOU, DISCUSSION FROM YOU. YOU, WHO ARE EXPERTS, THAT'S REALLY WHAT THIS IS ALL ABOUT. AGAIN, TO THOSE WHO KNOW THIS STUFF, PLEASE FORGIVE ME BUT SOME OF YOU MAY BE LESS FAMILIAR WITH THIS. AN NIH WORKING GROUP IS A FACT-FINDING BODY. YOU'RE HERE TO GATHER INFORMATION. YOU CAN CONDUCT SOME RESEARCH, ANALYZE WHATEVER RELEVANT ISSUES ARE PUT BEFORE YOU. AND YOU CAN INDEED DRAFT PROPOSED POSITION PAPERS. BUT THOSE HAVE TO BE DELIVERED FOR DELIBERATION BY A FEDERAL ADVISORY COMMITTEE, SO-CALLED FACA COMMITTEE. AND MANY OF YOU HAVE SERVED ON FACA COMMITTEES, SO YOU ARE AWARE OF THAT. WE HAVE TWO TYPES OF PEOPLE ON WORKING GROUPS. AND INDEED, IN THIS ROOM, THERE ARE TWO TYPES OF YOU. SOME OF YOU ARE SPECIAL GOVERNMENT EMPLOYEES, SGEs. YOU ARE SERVING CURRENTLY ON AN NIH FEDERAL ADVISORY COMMITTEE, PROBABLY A NATIONAL ADVISORY COUNCIL. AND YOU'RE ALSO CONCOMITANTLY SERVING ON THIS WORKING GROUP. AS A SPECIAL GOVERNMENT EMPLOYEE, YOU HAVE -- YOU MAY BE WEARING TWO HATS BUT YOU ONLY HAVE ONE HEAD. AND SO YOU WILL REMAIN AN SGE EVEN THOUGH YOU'RE HERE ON THIS WORKING GROUP. AND SO AS SUCH, YOU WILL CONTINUE TO BE COVERED BY THE CONFLICT OF INTEREST STATUTES AND REGULATIONS. YOU'RE THE FOLKS FILING CONFIDENTIAL FINANCIAL DISCLOSURE REPORTS, YOU CAN'T DO THOSE ELECTRONICALLY, A BIG STEP FORWARD BUT THAT'S ANOTHER DISCUSSION FOR LATER IN MY DAY. AND YOU DO OF COURSE PROVIDE US WITH QUARTERLY UPDATES AS APPROPRIATE, AND YOU WILL FOLLOW THE DESIGNATED FEDERAL OFFICIAL'S DIRECTIONS, DR. BAKER, REGARDING RECUSAL OPERATIONS. EVEN THOUGH YOU'RE ON A WORKING GROUP YOU'RE STILL AN SGE, IF YOU ARE IN THAT BUCKET. THE OTHER GROUP OF YOU ARE NOT SGEs. AND YOU ARE HERE BECAUSE OF YOUR UNIQUE EXPERTISE AS IT RELATES TO THE NEEDS OF THE WORKING GROUP. NOW, OBVIOUSLY THE SGEs ARE ALSO EXPERTS, BUT YOU JUST HAPPEN TO BE ON NATIONAL ADVISORY COUNCILS, THEREFORE PROVIDE A GOOD LINK BACK TO FACA COMMITTEES. YOU'RE NOT HELD TO THE SAME ETHICS RULES AND REGULATIONS BUT YOU STILL ARE REQUIRED TO COMPLETE A CERTIFICATION PROCESS AS MANAGED BY THE DESIGNATED FEDERAL OFFICIAL. SO, WHAT ARE POTENTIAL SOURCES OF BIAS? I UNDERLINE POTENTIAL, BECAUSE PERCEPTION IS JUST AS IMPORTANT AS REALITY HERE. AND SO WE NEED TO BE COGNIZANT OF BOTH. IF IT COULD LOOK LIKE A BIAS, THEN WE NEED TO RAISE OUR HANDS AND, YOU KNOW, DISCUSS IT. SO, FOLLOWING INTEREST AND RELATIONSHIPS ARE POTENTIAL SOURCES OF BIAS, FOR YOURSELF OR MEMBER OF YOUR IMMEDIATE FAMILY. THAT IS NOT EMANCIPATED CHILDREN USUALLY. IF YOU HOLD A FINANCIAL EQUITY OR PATENT OR OTHER PROPRIETARY INTEREST IN AN ORGANIZATION WHOSE PRODUCT OR PRODUCT CONCEPT IS SUBJECT OF AND/OR COMPETES WITH A PRODUCT OR PRODUCT CONCEPT THAT IS SUBJECT TO DELIBERATIONS. IN OTHER WORDS, IF YOU HAVE AN EQUITY, THAT TOUCHES UPON WHAT'S BEING DISCUSSED, JUST LET US KNOW. DOESN'T MEAN THAT WE ASK YOU TO LEAVE THE ROOM. BUT IT DOES MEAN THAT YOU ACKNOWLEDGE THAT YOUR VIEW MIGHT IN SOME WAY EITHER BE POTENTIALLY BIASED OR THERE IS A PERCEPTION OF THAT BIAS. AND SECONDLY, IF YOU WOULD UNIQUELY BENEFIT FROM THE RESEARCH EMPHASIS IN A DEFINED AREA. WEL, THAT MAY BE ALL OF YOU, BECAUSE OF YOUR EXPERTISE, AND WE UNDERSTAND THAT, BUT, AGAIN, WHEN IN DOUBT, JUST LET'S TALK ABOUT IT. AND, AGAIN, IT'S NOT THAT YOU WOULD BE NECESSARILY EXCUSED FROM ANY OF THE DISCUSSIONS BUT AT LEAST WILL YOU HAVE ACKNOWLEDGED THAT THIS IS THE CIRCUMSTANCE. AND, AGAIN, THE OTHER SOURCE OF BIAS OR PERCEPTION OF BIAS IS IF EITHER YOU OR MEMBERS OF YOUR IMMEDIATE FAMILY ARE SEEKING EMPLOYMENT IN AN ORGANIZATION THAT IS EITHER INVOLVED WITH THE PRODUCT CONCEPT THAT'S THE SUBJECT OF DISCUSSION OR IMPORTANTLY COMPETES WITH A PRODUCT OR PRODUCT CONCEPT TO BE DISCUSSED. SO, IT'S NOT ONLY THAT YOU ARE INVOLVED WITH COKE ZERO, BUT YOU ALSO HAVE BEEN A POTENTIAL BIAS WITH PEPSI. I THINK I GOT THAT RIGHT. SO, OKAY. OKAY. SO, HOW TO IDENTIFY AND RESOLVE CONFLICTS, IF YOU'RE AN SGE, PLEASE EXCUSE YOURSELF FROM DISCUSSIONS OF SPECIFIC MATTERS THAT COULD AFFECT INTEREST AND RELATIONSHIPS IDENTIFIED ON YOUR RECUSAL LIST BECAUSE YOU ALREADY HAVE THAT. IF YOU'RE NOT SURE, DR. BAKER CAN DISCUSS THAT WITH YOU. AND OBVIOUSLY WE'D LIKE YOU TO COMPLETE THE CERTIFICATION PROCESS, AS DR. BAKER OUTLINES, AND FOR YOUR NON-SGEs, PLEASE READ THE CONFLICT OF INTEREST AND CONFIDENTIALITY INFORMATION FOR WORKING GROUP PARTICIPANTS, REVIEW THE WORKING GROUP CHARGE AND MEETING AGENDA. THAT GIVES YOU THE LAY OF THE LAND. DO THE INTERSECTION IN YOUR BRAIN, TO SEE IF THERE'S ANY POTENTIAL FOR BIAS OR REAL BIAS. PLEASE READ CERTIFICATION YOU HAVE A POTENTIAL OR ACTUAL COI WITH AN AGENDA ITEM FOR EACH MEETING, AND THEN PLEASE DISCLOSE THAT TO THE DESIGNATED FEDERAL OFFICIAL, DR. BAKER, AND THE WORKING GROUP, PRIOR TO ANY DISCUSSIONS. SO IN OTHER WORDS, BY THE WAY, TEN YEARS AGO I WAS RESEARCHING SOMETHING RELATED TO Y. OKAY? THAT'S USUALLY WHAT HAPPENED. OR 26 YEARS AGO, A FRIEND OF MINE, YOU KNOW, THAT'S SORT OF THING. BUT, AGAIN, PLEASE DO DISCLOSE. LET'S ERR ON THE SIDE OF OVERDISCLOSURE. AND THAT WAY, THERE CAN BE NO PLACE IN THE MINUTES SO THAT INDEED IT WAS DECLARED -- YOU DECLARED EITHER PERCEPTION OR REAL BIAS, AND ALSO THE DETERMINATION AS TO HOW WE WOULD HANDLE THAT. IN SOME INSTANCES WE'LL ASK YOU TO EXCUSE YOURSELF, OR YOU MAY SAY IT'S APPROPRIATE FOR ME TO RECUSE MYSELF. THAT'S FINE. YOU'LL STEP OUT FOR A FEW MOMENTS. THOSE IN STUDY SECTIONS AND ON COUNCIL KNOW HOW THAT WORKS. ONCE THE DISCUSSION IS CONCLUDED THEN OF COURSE YOU'LL BE INVITED BACK IN. SO, FINALLY, JUST AS A REMINDER, THE MATERIALS MADE AVAILABE ARE STRICTLY CONFIDENTIAL, AND MAY NOT BE DISCLOSED OR DISCUSSED WITH ANYONE WHO HAS NOT BEEN OFFICIALLY DESIGNATED TO PARTICIPATE IN THE WORKING GROUP MEETING, AND YOU WILL CERTIFY THAT YOU'LL MAINTAIN THAT CONFIDENTIALITY. AND SO, WITH THAT, I WILL TURN IT BACK TO DR. BAKER UNLESS THERE ARE ANY SPECIFIC QUESTIONS. I'LL BE SORT OF ON CALL TOGETHER WITH MY COLLEAGUES, HOLLY BECKERMAN JAFFE AND DR. TARA SCHWETZ. IF ANY SPECIFIC QUESTION COMES UP WE NEED TO NAVIGATE DR. BAKER WOULD LIKE ADDITIONAL CONSULTATION WITH, WE WILL BE AVAILABLE AND CAN COME DOWN AND HAVE A QUICK SIDEBAR. SO WITH THAT, I'LL TURN IT BACK TO -- >> THANK YOU, DR. TABAK. FOR THIS MEETING WE DID NOT PROVIDE ANY MATERIALS THAT SHOULD REMAIN CONFIDENTIAL. THAT MAY BE IN FUTURE MEETINGS. SO, EVERYTHING THAT WE'RE DISCUSSING TODAY IS PUBLIC. IT IS BEING VIDEOCAST. AND THE MATERIALS WERE POSTED ONLINE, SO THIS IS A PUBLIC MEETING AND ALL OF OUR DISCUSSIONS WILL BE MADE PUBLIC. WITH THAT I'D LIKE TO GO AROUND THE TABLE AND GIVE EVERYONE A CHANCE TO INTRODUCE THEMSELVES. I'M REBECCA BAKER, DIRECTOR OF HEAL INITIATIVE, HERE AT NIH. AND VERY GRATEFUL TO BE GETTING TO KNOW THIS WORKING GROUP, AND LOOKING FORWARD TO OUR DISCUSSIONS. DR. BIANCHI? >> DIANA BIANCHI, DIRECTOR OF THE EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT WITH PARTICULAR INTEREST IN NEONATAL OPIOID WITHDRAWAL SYNDROME, BUT OUR INSTITUTE ALSO COVERS A LOT OF ISSUES RELATED TO REPRODUCTIVE HEALTH, AND SO WE'RE PARTICULARLY INTERESTED IN THE PAIN PART AS WELL, BECAUSE WE HAVE A RESEARCH PORTFOLIO IN SOME PAINFUL GYNECOLOGIC CONDITIONS SUCH AS ENDOMETRIOSIS. >> GOOD MORNING, EVERYBODY. IT'S A PLEASURE TO BE HERE WITH YOU. I'M NORA VOLKOW, I DIRECT THE NATIONAL INSTITUTE ON DRUG ABUSE. >> GOOD MORNING, I'M FRANCIS COLLINS, DIRECTOR OF THE NATIONAL INSTITUTES OF HEALTH, SPEAKING TO YOU IN A BIT ABOUT THE SORT OF 30,000-FOOT VIEW OF THE HEAL INITIATIVE. I WILL TELL YOU THIS IS AN ALL-CONSUMING EFFORT ACROSS NIH, WELL IT SHOULD BE. THIS IS A NATIONAL CRISIS THAT DESERVES EVERY BUILT OF ENERGY WE CAN PUT IT INTO. WE'LL IN THE ALL-HAND-ON-DECK APPROACH, AND THIS WORKING GROUP IS A CRITICAL PART OF HOW WE HOPE IN THE NEXT FEW MONTHS TO MAKE MAJOR INVESTMENTS OF ABOUT $850 MILLION TO TRY TO BE SURE WE'RE BRINGING ALL THE BEST IDEAS, BOTH TO THE TREATMENT AND PREVENTION OF ADDICTION, AND TO THE DEVELOPMENT OF OTHER APPROACHES TO MANAGE CHRONIC PAIN THAT ARE NOT ADDICTIVE. >> SO, AGAIN, LARRY TABAK, DEPUTY DIRECTOR, I DO A NUMBER OF THE THINGS THAT FRANCIS CAN'T DO, OR DOESN'T WANT TO DO. AND AS DEPUTY ETHICS COUNSELOR, AS YOU JUST HEARD, I TELL EVERYBODY ELSE THEY CAN'T DO WHAT THEY DO WANT TO DO. [LAUGHTER] >> I'M WALTER KOROSHETZ, DIRECTOR OF THE NEUROLOGIC INSTITUTE, AND HAVE THE PRIVILEGE OF WORKING WITH THE OTHER I.C. DIRECTORS COORDINATING PAIN RESEARCH AT NIH IN TERMS OF THE PAIN CONSORTIUM, WHICH IS A GROUP THAT'S BEEN IN ACTION FOR ABOUT A DECADE, COORDINATING PAIN RESEARCH, AND THEN CHAIR THE INTERAGENCY PAIN RESEARCH COORDINATING COMMITTEE. SO WE'VE BEEN WORKING WITH FRANCIS AND REBECCA AND LARRY ON TRYING TO PUT FORWARD SOME OPPORTUNITIES TO DEVELOP BETTER AND MORE EFFECTIVE PAIN MEDICINES THAT ARE NON-ADDICTIVE. THANKS. >> GOOD MORNING, DIRECTOR OF NATIONAL CENTER FOR COMPLEMENTARY AND INTEGRATIVE HELD, INTERESTED IN NON-PHARMACOLOGIC APPROACHES TO PAIN AS WELL AS ASSISTING IN MANAGEMENT OF OPIOID USE DISORDERS. >> HI, THANK YOU FOR ALL YOUR EFFORTS. IT'S GOING TO BE AMAZING. I'M DIRECTOR OF -- I'M MARTHA SOMERMAN. AS MANY OF YOU HAVE EXPERIENCED DENTAL PAIN, WE'RE INTERESTED IN ALTERNATIVE APPROACHES AS WELL. THANK YOU. >> SHARON HENRY, UNIVERSITY OF VERMONT, BACKGROUND AS NEUROBIOLOGY IST AND PHYSICAL THERAPIST, WORKING WITH CHRONIC LOW BACK PAIN FOR 30 YEARS, SINCE RETIRING I HAVE BEEN AT THE UNIVERSITY OF VERMONT MEDICAL CENTER WHERE I WAS INTERFACING WITH PRIMARY CARE AND PHYSICAL THERAPY, TRYING TO GET THEM TO COLLABORATE MORE AND USE TOOLS AVAILABLE TO HELP THIS POPULATION, AND SO I HAVE A NEW APPRECIATION FOR IMPLEMENTATION SCIENCE. SOME OF THE CHALLENGES THAT FACE US AS WE TRY TO USE THE GREAT SCIENCE WE'RE GOING TO DISCUSS GETTING INTO THE CLINIC IN THE HANDS OF CLINICIANS ON THE FOREFRONT. I'M LOOKING FORWARD TO WORKING WITH THIS COMMITTEE AND ALL THE DISCUSSIONS. THANK YOU. >> I'M WALLY SMITH, GENERAL INTERNIST BY TRAINING, HEALTH& SERVICES RESEARCHER, IMPLEMENTATION SIGNIST, SICKLE CELL DOC, INHERITED UNWANTED PATIENTS IN 198 AT UNIVERSITY TENNESSEE, LEFT THERE TO GET AWAY FROM THAT, RAN INTO IT AGAIN AT VIRGINIA COMMONWEALTH UNIVERSITY IN 1991, HAVE BEEN TAKING CARE OF SICKLE CELL PATIENTS FOR 30-SOME YEARS, BACKED INTO PAIN BECAUSE OF THE OBVIOUS HIGH PAIN BURDEN IN SICKLE CELL DISEASE, WE CONDUCTS THE PISCES STUDY WHICH LAID OUT EPIDEMIOLOGY, DISCOVERED PAIN PREDOMINATES IN SICKLE CELL DISEASE, LEADING TO NEUROLOGY RFA IN NHLBI ON SICKLE CELL PAIN AND SO WE HAVE BEEN DOING A LOT OF WORK WITH THE IPRCC AND A LOT OF OTHER AGENCIES LOOKING TO TRY TO TAKE CARE OF CHRONIC PAIN WHILE SAFELY PRESCRIBING AND USING OPIOIDS APPROPRIATELY AND FINDING PATIENTS WHO ARE AT RISK FOR ADDICTION AND MANAGING THEM. >> GOOD MORNING, ROB GIREAX, WASHINGTON UNIVERSITY ST. LOUIS, DIRECTOR OF WASH U PAIN CENTER, INVOLVED IN TOUCHING ON ALL ASPECTS OF PAIN RESEARCH EDUCATION AND TREATMENT AND VERY INTERESTED IN THE WORK WE'RE GOING TO DO HERE. THANKS. >> JUDY PAICE, ADVANCED PRACTICE NURSE ON FACULTY AT NORTHWESTERN UNIVERSITY FEINBERG SCHOOL OF MEDICINE MOSHINGS OF -- MOST OF MY WORK IS CLINICAL CARE, CANCER, SICKLE CELL, HEMOPHILIA, RESEARCH ON LONG-TERM TREATMENT CAUSING PAINFUL SYNDROME. >> GOOD MORNING, KEN VERBURG, WITH PFIZER. I'VE BEEN IN THE RESEARCH AND DEVELOPMENT AREA FOR PFIZER FOR MANY, MANY YEARS, A COUPLE DECADES AT LEAST. HAD BROAD RESPONSIBILITIES OVER A NUMBER OF THERAPEUTIC AREAS OVER TIME BUT SPENT THE LION'S SHARE FOCUSED ON PAIN THERAPEUTICS, AND SO PARTLY TO BLAME FOR WHERE WE ARE TODAY. AND HOPEFULLY WE CAN WORK TOGETHER TO MOVE FORWARD. >> HI, CHRIS VEASLEY, I'VE HAD CHRONIC PAIN FOR 30 YEARS BEING INVOLVED IN A CAR ACCIDENT AT A TEENAGER, I DO NEUROSCIENCE RESEARCH AT HOPKINS, OUR ORGANIZATION FOCUSES ON PATIENT POPULATION THAT HAS MULTIPLE COEXISTING CHRONIC PAIN CONDITIONS. W ADVANCE RESEARC ON THOSE DISORDERS, WORK ON THE KNOWLEDGE TRANSLATION PIECE TO REDUCE TIME IT TAKES FOR RESEARCH FINDINGS TO ENTER CLINICAL CARE AND WORK WITH FEDERAL AGENCIES IN BIOPHARMACEUTICAL INDUSTRY TO ADVANCE TREATMENTS FOR THESE CONDITIONS. >> HI, LYNN DEBAR, KAISER PERMANENTE WASHINGTON HEALTH RESEARCH INSTITUTE IN SEATTLE, WHICH UNTIL RECENTLY WAS GROUP HEALTH. ALSO AFFILIATE POSITION IN PSYCHIATRY AT UNIVERSITY OF WASHINGTON. I'M A BEHAVIORAL HEALTH RESEARCHER, CLINICAL PSYCHOLOGIST BY TRAINING, I DO LARGE SCALE EPIDEMIOLOGICAL AND PRAGMATIC TRIALS, PRIMARILY FOCUSED ON COMPLEX PATIENTS WITH COMORBID CONDITIONS, WITH CHRONIC PAIN. MOST OF IT EMBEDDED INTO PRIMARY CARE SETTINGS. I'M ALSO ON COUNCIL AT NCCIH. >> RICK KUNTZ, CARDIOLOGIST, WORK IN MEDICAL TECHNOLOGY INDUSTRY. WE HAVE VARIOUS DEVICES FOR PAIN THERAPY. >> TERRY JERNIGAN, PROFESSOR AT UC SAN DIEGO, AND DIRECTOR OF AN INTERDISCIPLINARY RESEARCH UNIT, CENTER FOR HUMAN DEVELOPMENT, RESEARCH IS COGNITIVE NEUROSCIENCE, A RELEVANT ROLE FOR MY PARTICIPATION IS MY ROLE AS CO-DIRECTOR WITH SANDRA BROWN OF ADOLESCENT BRAIN AND COGNITIVE DEVELOPMENT, ABCD STUDY. IT'S A LARGE SCALE LONGITUDINAL STUDY, CONDUCTED AT 21 U.S. INSTITUTIONS OF ALMOST 12,000 YOUNGSTERS AND THEIR FAMILIES, WHICH IS A DEEP DIVE INTO THE PROMISE AND PERILS OF ADOLESCENCE, SHALL WE SAY, FROM A BIOMEDICAL PERSPECTIVE. AND I PREVIOUSLY SERVED ON NIDA COUNCIL AND COUNCIL OF COUNCILS. >> HELLO, ERIC GARLAND, THANK YOU FOR BRINGING ME HERE. IT'S A HUGE HONOR. I'M A PROFESSOR AND ASSOCIATE DEAN FOR RESEARCH UNIVERSITY OF UTAH COLLEGE OF SOCIAL WORK, AND DIRECTOR OF THE CENTER ON MINDFULNESS AND INTEGRATIVE HEALTH INTERVENTION DEVELOPMENT. I'M A LICENSED CLINICAL SOCIAL WORKER BY TRAINING, BUT A BIOBEHAVIORAL CLINICAL RESEARCHER, MY WORK FOCUSES ON TRANSLATING FINDINGS FROM COGNITIVE AND AFFECTIVE NEUROSCIENCE INTO BEHAVIORAL THERAPIES FOR THE TREATMENT OF CHRONIC PAIN AND ADDICTION PARTICULARLY OPIOID MISUSE, I'M VERY INTERESTED IN MINDFULNESS THERAPIES AND EFFECT ON STRUCTURING THE REWARD SYSTEM. >> GOOD MORNING, PATRICE HARRIS, PRESIDENT ELECT OF THE AMERICAN MEDICAL ASSOCIATION AND ALSO CHAIR THE AMA OPIOID TASK FORCE, THAT WAS CONVENED IN 2014 WITH PURPOSE OF BETTER COORDINATING AND COLLABORATING EFFORTS OF THE PHYSICIAN COMMUNITY TO ADDRESS THIS ISSUE, AND ALSO TO COORDINATE AND COLLABORATE WITH MULTI-DISCIPLINARY PARTNERS TO ADDRESS THIS ISSUE. I'M A CHILD AND ADOLESCENT PSYCHIATRIST BY TRAINING, WITH SOME EXPERTISE IN ADDICTION AS WELL. CURRENTLY I SEE A LOT OF CHILDREN AND ADOLESCENTS IN MY PRACTICE WHO HAVE BEEN TRAUMATIZED, AND I SEE A LOT OF CHILDREN WHO ARE CURRENTLY IN THE CHILD WELFARE SYSTEM, PARTLY AS A RESULT OF PARENTS WHO MAY BE DEALING WITH ADDICTION AND OTHER SUBSTANCE USE DISORDERS. >> GOOD MORNING, MY NAME IS CHRISTIAN HEIDBREDER, CHIEF SCIENTIFIC OFFICER, FOR TEN YEARS. BACK IN 2010, WE DEVELOPED AND GOT REGULATORY APPROVAL OF (INDISCERNIBLE) AND IN 2017 THE APPROVAL OF THE FIRST MONTHLY BUPRENORPHINE INJECTABLE FOR THE TREATMENT, AND I'M VERY PLEASED TO BE HERE WITH YOU TODAY. >> GOOD MORNING, DR. ANDRE JONES, PROFESSOR IN OBSTETRICS AND GYNECOLOGY UNC-CHAPEL HILL, AN HONOR TO BE HERE. I'M A PSYCHOLOGIST BY TRAINING, EXPERIMENTAL AND CLINICAL, AND MY EXPERTISE PERTINENT TO THIS COMMITTEE WILL BE AROUND LOOKING AT PRENATAL OPIATES AND OTHER TYPES OF EXPOSURES. WE'VE DONE RANDOMIZED CONTROL TRIALS COMPARING BUPRENORPHINE TO METHADONE, RELATIVE SAFETY AND EFFICACY FOR FETUS, MOTHER, AND CHILD, IN TERMS OF HOW THESE MEDICATION ALSO HAVE SHORT-TERM AND LONG-TERM OUTCOMES, AND THEN WE'RE ALSO LOOKING AT OTHER TIMES OF MEDICATIONS, INCLUDING NALOXONE TO TREAT OPIOID USE DISORDER IN PREGNANT WOMEN, WE'RE VERY -- I ALSO RUN A CLINIC THAT SERVES A NUMBER OF ABOUT 250 WOMEN AND THEIR CHILDREN EVERY YEAR, THAT'S A COMPREHENSIVE INTEGRATED CLINIC, I BRING CLINICAL EXPERTISE SO IT'S NOT MOTHER VERSUS CHILD BUT MOTHER AND CHILD AND HELPING TO FIND THE BEST SOLUTIONS FOR BOTH. >> I'M NED NUNES, ADDICTION PSYCHIATRIST AND PROFESSOR OF PSYCHIATRY AT COLUMBIA UNIVERSITY MEDICAL CENTER IN NEW YORK STATE, SPENT MY CAREER DOING CLINICAL TRIALS FOR ADDICTIONS, PARTICULARLY OPIATE USE DISORDER. PRINCIPAL INVESTIGATOR IN THE NIDA CLINICAL TRIALS NETWORK WHICH IS GEARING UP TRYING TO GEAR UP TO DO A NUMBER OF STUDIES TO CONTRIBUTE TO FIGURING OUT HOW TO BETTER TREAT OPIATE USE DISORDER, PARTICULARLY HOW TO KEEP PATIENTS ON THE MEDICATIONS THAT WE HAVE THAT WE KNOW WORK WELL AND IF WE CAN KEEP PATIENTS ON THEM, AND I ALSO SIT ON NIDA COUNCIL. >> HI, CONNIE WEISNER, AT THE DIVISION OF RESEARCH, KAISER PERMANENTE NORTHERN CALIFORNIA, AND ALSO AT UCSF DEPARTMENT OF PSYCHIATRY. I'M HAPPY TO BE HERE, SUCH AN IMPORTANT TIME AND TOPIC. I'M A P.I. OF ONE OF THE CLINICAL TRIAL NETWORK NODES THAT'S MADE UP OF 18 HEALTH SYSTEMS ACROSS THE COUNTRY, AND THROUGH THAT AND AT KAISER PERMANENTE NORTHERN CALIFORNIA WE ARE DOING A VARIETY OF STUDIES. WE JUST FINISHED A TRIAL LOOKING AT DIFFERENT WAYS OF HELPING PEOPLE WITH PAIN AS THEY ARE BEING TAPERED FROM MEDICATIONS. IT'S A HUGE INITIATIVE HAPPENING THROUGHOUT THE HEALTH SYSTEM. ANOTHER TRIAL LOOKING AT LENGTH OF TIME, I MEAN, EXCUSE ME, INTENSITY OF PSYCHOSOCIAL TREATMENTS TO GO ALONG WITH SUBOXONE, AND WE HAVE AN OPIOID REGISTRY THAT'S BEING EXPANDED TO OTHER SITES TO LOOK AT RISKS FOR ADVERSE EVENTS AND SOME PREDICTIVE MODELING THERE. AND I'M ON THE NIAAA COUNCIL RIGHT NOW AND HAVE BEEN ON THE NIDA COUNCIL. THANK YOU. >> I'M JESSICA NICOL, FOUNDER OF ADDICTION POLICY FORM, WORK WITH FAMILIES STRUGGLING WITH SUBSTANCE USE DISORDER, HELP TRANSLATE KNOWLEDGE AND SCIENCE TO OUR PATIENTS AND FAMILY AND FIELD COMMUNITY, WE'RE WORKING HARD ON ADVOCACY AND AWARENESS PARTICULARLY HOW WE TACKLE STIGMA, HONORING TO HERE TODAY. >> GOOD MORNING. LAST AND MAYBE LEAST, BOB CARTER, NATIONAL INSTITUTION OF ARTHRITIS AND SKIN DISEASE. PAIN IS ALMOST THE DEFINITION OF SOME DISORDERS, BUT OUR ROLE IN THE HEAL INITIATIVE IS BACPAC, A BACK PAIN CONSORTIUM. THANK YOU. >> OKAY. THANK YOU, EVERYONE. I CAN TELL THAT WE ARE READY TO GET TO WORK BECAUSE WE ARE GOING REALLY FAST, AND GOOD ON TIME. BEFORE I ASK JESSICA NICKEL TO SPEAK, IS ALLAN BASBAUM ON THE LINE? WE HAVE ONE ADDITIONAL WORKING GROUP MEMBER, DR. ALLAN BASBAUM OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO. HE HAD A CONFLICT TODAY BUT WAS POSSIBLY GOING TO JOIN BY PHONE. ALLAN, ARE YOU THERE? OKAY. THANK YOU. JESSICA HULSEY NICKEL. >> THANK YOU SO MUCH. I THOUGHT IT WOULD BE HELPFUL AND I WAS SO GLAD TO BE INVITED TODAY SO WE CAN CHAIR A LITTLE BIT ABOUT OUR PATIENT AND FAMILY PERSPECTIVE. WE'RE A RELATIVELY NEW ORGANIZATION, AND I'M SORRY, I HAVE THAT SPECIAL COLD THAT'S GOING AROUND. I'M NOT HICCUPPING, I'M TRYING TO COVER UP MY SINUS INFECTION. WE'RE RELATIVELY NEW ORGANIZATION. THIS MONTH IS OUR FOURTH BIRTHDAY. AND WE'RE TRYING TO FOLLOW THE FOOTSTEPS OF EVERY OTHER PATIENT ADVOCACY GROUP THAT'S OUT THERE. AND REALLY REPRESENT OUR PATIENTS AND FAMILIES, TRANSLATE INFORMATION THAT CAN BE COMPLICATED FOR THE LAYPERSON, BUT ALSO REALLY COMPLICATED WHEN YOU'RE IN CRISIS OR YOU HAVE A COGNITIVE DISORDER. AND WE WORK REALLY HARD TO MAKE SURE THAT WE REACH PEOPLE HAVING THEIR DARKEST DAY, IN CRISIS, DROWNING, FIGURING OUT HOW TO HELP A LOVED ONE OR HELP THEMSELVES, AND NOT ALWAYS KNOWING WHERE TO GO. I HAVE BEEN IN THIS FIELD FOR LONGER THAN FOUR YEARS, I'M NOT GOING TO SAY HOW MANY. I'LL GIVE MY AGE AWAY. BUT I AM AN IMPACTED FAMILY MEMBER. I LOST BOTH MY PARENTS TO HEROIN USE DISORDER AND GOT INVOLVED TO CHANGE WHAT HAPPENS WHEN THIS DISEASE HITS YOUR FAMILY. BECAUSE IT IS ISOLATING, AND STIGMATIZED, AND DIFFICULT TO NAVIGATE. WE'RE MORE LIKELY TO BE TAKEN ADVANTAGE OF THAN TO FIND ONE OF THE AMAZING MEDICAL CENTERS OR PHYSICIANS AROUND THIS TABLE. WE HAVE A BIG VISION TO BRING HELP TO PEOPLE IN CRISIS IT'S, ALSO AIM ADDICTION AS A HEALTH PROBLEM, AIMING FOR THE STARS, WE BELIEVE WORKING WITH SCIENTISTS, RESEARCHERS, FOLLOWING THE SCIENCE IS INCREDIBLY IMPORTANT. WE'RE MIRED IN MYTH AND MISCONCEPTION WITH THIS DISEASE. WHAT WE'VE LEARNED WITH WORKING WITH PATIENTS AND FAMILIES, IT'S NOT ONLY THAT WE HAVE TO EDUCATE, WE HAVE TO UNEDUCATE AND REEDUCATE. THERE ARE SO MANY MYTHS FROM THIS BEING A MORAL FAILING TO BEING ABLE TO FIX IT IN 28 DAYS, THAT'S ONE OF MY FAVORITE ONES, LIKE THE EXIT DOOR OF FANCY SPA-LIKE TREATMENT CENTERS ARE MAGIC PORTALS TO HEALTHINESS. LIKE DISMANTLING SOME OF THE MYTHS AND THEN FOLLOWING UP WITH THE REAL INFORMATION THAT'S SO IMPORTANT. ONE OF OUR FIRST PIECES THAT WE DID WAS TO TAKE NORA'S SCIENCE AND RESEARCH AND TURNED IT INTO CARTOONS AND SENT IT INTO THE WORLD, AND HAVE COMMUNITY TRAINERS OUT THERE MAKING SURE WE'RE BETTER DESCRIBING ADDICTION, ADDICTION AS A BRAIN DISEASE, BRAIN DISORDER, TAKING TIME TO MAKE SURE THAT STICKS. BRIEFLY BEFORE I GET INTO PATIENT AND FAMILY STORIES, WE TRY TO HELP PATIENTS AND FAMILIES IN CRISIS WITH A 24/7 TELEHEALTH CENTER MANNED BY LICENSE WORKERS. LAST YEAR WE HELPED CONNECT THEM TO THE RIGHT SERVICES. WE HOPE THAT ONLY GROWS. ADVOCACY AND EDUCATION IS SO IMPORTANT BECAUSE LOTS OF STIGMA, RIGHT? HOW DO YOU -- HALF OF THE COUNTRY DOES NOT BELIEVE ADDICTION IS A HEALTH CONDITION. AND SO WE'RE REALLY FOCUSED ON THAT HALF OF THE COUNTRY AND HOW DO WE MAKE SURE WE CHANGE THOSE MINDS. MAKING SURE THAT WE BRING THIS MORE INTO MEDICINE, INSTEAD OF EXTERNAL TO MEDICINE, WE DON'T FIND THE DOCTORS, WE DON'T HAVE ACCESS TO THE TREATMENTS AND MEDICINES THAT ARE THERE IS A HIGH PRIORITY. THAT TRANSLATING THE SCIENCE IS SO IMPORTANT TO US. ONE OF THETHINGS THAT'S IMPORTANT FOR US IS TO BE FACE AND VOICES FOR OUR PATIENTS AND FAMILIES. AND AS YOU ALL KNOW, WE KNOW THE NUMBERS ARE STILL GOING IN THE WRONG DIRECTION OVERDOSE DEATH, 192 PEOPLE A DAY, BUT DON'T ALWAYS DIG DOWN INTO THESE ARE REAL FAMILIES AND LOVED ONES, REAL ADOLESCENTS AND ADULTS, SIBLINGS AND SONS AND DAUGHTERS. I THOUGHT I WOULD SHARE A LITTLE BIT OF OUR STORIES AND WHO WE ARE. CASSIDY'S MOM DESCRIBES HER AT PURE SUNSHINE, AND SHE DIED WAY TOO EARLY FROM AN OVERDOSE FROM FENTANYL. AND HER MOM WROTE A BEAUTIFUL LETTER FOR OUR 192 A DAY CAMPAIGN, AND DESCRIBES HOW HER LAUGHTER WOULD FILL THE ROOM WITH SUNSHINE. THIS IS ANTHONY, HIS BROTHER GENO WROTE A LETTER, HE LIKED TO COOK FOR HIS FAMILY, DIED WAY TOO YOUNG FROM OVERDOSE. HIS BROTHER DESCRIBES ADDICTION AS A MERCYLESS DEVIL. THIS IS EMMITT. EMMITT'S MOTHER AMY RUNS OUR SERVICES AND PROGRAMS IN MASSACHUSETTS, HE WAS IN COLLEGE, 19 YEARS OLD, AND HE HAD STARTED STRUGGLING WITH ADDICTION IN HIGH SCHOOL FROM K-2 SPICE, SO SYNTHETICS, BUT THOUGHT THEY TACKLED THAT. HE WENT TO COLLEGE, FAMILY UNAWARE HE RELAPSED. AND AFTER THEY LOST HIM TO A HEROIN OVERDOSE THEY LEARNED HE HAD SEVEN OVERDOSES REVERSED IN AREA HOSPITALS, THERE HAD NEVER BEEN NOTIFICATION OF HIS FAMILY OR EVEN HIS PRIMARY CARE PROVIDERS BECAUSE OF MISINTERPRETATION OF HIPAA REQUIREMENTS. SO HOW DO WE MAKE SURE WE CHANGE AND USE NON-FATAL OVERDOSES AS A WARNING SIGN TO INITIATE TREATMENT AND TO WRAP UP THAT PATIENT AND THAT FAMILY? THIS IS APRIL. APRIL'S MOTHER SAID THE WORST PART OF LOSING HER DAUGHTER WAS SHE HAD TO TELL HER 4-YEAR-OLD GRANDDAUGHTER HER MOMMY WASN'T COMING HOME. WE ALSO HAVE FOUND HEART-BREAKINGLY WE'RE LOSING MORE THAN ONE FAMILY MEMBER AT A TIME. PARTICULARLY WE KNOW THAT IF IT'S AN OLDER SIBLING WHO STARTS TO DEVELOP SUBSTANCE USE DISORDER CAN HAVE AN IMPACT ON YOUNGER SIBLINGS. AND WE KNOW THE LOSS OF A FAMILY MEMBER CAN ALSO BE A TRIGGER FOR RELAPSE. SO THIS IS MATTHEW AND DILLON. THEY WERE FOUR YEARS APART, BORN ON THE SAME DAY. AND THEIR MOTHER IS AMAZING. SHE WROTE THIS BEAUTIFUL LETTER, SHE SAID, HAD THEY STRUGGLED WITH SKIN CANCER, THERE WOULD HAVE BEEN THE DOCTORS AND TREATMENTS AND FOLLOW-UP. AND THE CARE THEY NEEDED. BUT THEY STRUGGLED WITH ADDICTION. SHE LOST BOTH HER BOYS. AND WOULD LIKE TO USE THAT FIRE IN HER BELLY AND THAT GREASE TO CHANGE WHAT HAPPENS FOR OTHER FAMILIES. SO IN TERMS OF JUST GIVING SOME GENERAL FEEDBACK FROM WHERE WE SIT AS PATIENTS AND FAMILIES, NOT JUST THOSE THAT HAVE LOST A LOVED ONE, LIKE ME, AND AMY, AND GENO AND OTHERS, BUT ALSO FOR OUR PATIENTS WHO ARE IN RECOVERY, FOR FAMILIES IN RECOVERY, AND WE HAVE A GROWING POPULATION WITHIN OUR ORGANIZATION OF THOSE THAT HAVE AN ACTIVE USE DISORDER. WHICH CAN FEEL VERY STIGMATIZING AND ISOLATING. AND WHAT WE REALLY WANT IS WHAT OTHER DISEASES HAVE, RIGHT? TAKE, FOR EXAMPLE, CANCER. WE WOULD LIKE TO HAVE INDIVIDUALIZED CARE, NOT ONE-SIZE-FITS-ALL. WE WOULD LIKE TO BE ABLE TO FIND THE DOCTORS AND SPECIALISTS THAT CAN TREAT OUR ILLNESS. WHEN YOU GO ON GOOGLE THE FIRST 83 PATIENTS ARE BAD ACTORS AND PATIENT BROKERRERS, MORE LIKELY TO CONNECT US TO SOMEONE TO TELL US HOW TO GET A SECOND MORTGAGE OUR HOME THAN GET CARE. DOZENS OF FAMILIES HAVE GONE BANKRUPT, LIQUIDATED 401(k) ACCOUNTS FOR CARE THAT DIDN'T WORK. IT WASN'T THE RIGHT INDIVIDUALIZED CARE. OFTENTIMES THERE ISN'T EVEN A PHYSICIAN OR PROPER NUMBER OF PATIENTS TO PHYSICIAN RATIO IN CENTERS THEY FIND. WE WOULD LIKE TO HAVE MORE MEDICATIONS, NOT FEWER, RIGHT? WE WOULD LIKE TO HAVE MORE MEDICATIONS PARTICULARLY MORE METHAMPHETAMINE USE DISORDER, FAMILIES ARE TELLING US IS ON THE RISE, FOR ALCOHOL USE DISORDER, WHICH CONTINUES TO BE A REALLY SERIOUS CONCERN, SORT OF -- WE FIND NOT A LOT OF OUR PATIENTS ARE JUST USING ONE SUBSTANCE. WE HAVE A POLY DRUG ISSUE, THE MORE MEDICINES THE BETTER. ALSO PUT UP SOMETHING ABOUT TESTING YOUR BLOOD, WE WOULD LIKE TO HAVE WHAT MAY BE DIABETES, TYPE 2 DIABETES PATIENTS HAVE, UNDERSTANDING THIS IS A CHRONIC CONDITION, AND HOW WE HAVE LONG TERM CARE AND MYTHS LIKE 28 DAYS FOR THE MAGIC PORTALS OF HEALTHINESS AND I WAS TALKING TO AMAZING PHYSICIAN, THEY ARE LIKE, YOU KNOW, YOU DON'T GO TO SOMEONE'S SCHIZOPHRENIA GRADUATION CEREMONY, OR YOU DON'T SAY, OH, I'M SO SORRY YOU WERE DIAGNOSED WITH DIABETES, SO GLAD YOU'RE GOING TO BE DONE IN 30 DAYS, THAT WILL BE CURED. SO WE'D REALLY LIKE TO FIGURE OUT AND HAVE ACCESS TO THE PIECES THAT HELP US MANAGE THIS CHRONIC CONDITION TO HAVE BETTER PATIENT OUTCOMES. LAST I WOULD FOLLOW UP WITH SOME GENERAL STUFF. THERE'S SO MUCH STIGMA AROUND THIS DISEASE, AND IT IS NOT JUST IN THE MEDIA AND MOVIES OR IN OUR SCHOOL SYSTEMS. IT'S IN MEDICINE AS WELL. IT'S IN CHILD WELFARE SYSTEMS, CRIMINAL JUSTICE SYSTEMS, IT'S IN OUR HOMES, OUR SCHOOLS, OUR CHURCHES, OUR COMMUNITIES. TAKING ON HALF OF THE COUNTRY WHO SEES THIS AS A MORAL FAILING, IT'S TRICKY. HOWEVER, STIGMA KEEPS US FROM COMING OUT OF THE SHADOWS, AND ASKING FOR HELP, FROM INTERVENING EARLY. I HAVE THREE SONS AT HOME. IF I HAVE A HEALTH THING I'M WORRIED ABOUT, SOMEONE HAS FLU OR BROKEN ANKLE, I GO TO FACEBOOK, ASK MY FRIENDS. WHEN OUR FAMILIES ARE STRUGGLING WITH SUBSTANCE USE DISORDER, THEY DON'T GO TO FACEBOOK. OFTENTIMES THEY DON'T TELL THEIR FRIENDS, THEIR FAMILY, THEIR OWN NETWORKS, BECAUSE OF THE SHAME AND STIGMA THAT EXISTS. WE SEE WHERE THAT COMES FROM, BECAUSE OF THE RIDICULE AND THE NASTINESS THAT COMES BACK ON OUR FAMILIES WHEN THIS IS MADE PUBLIC. AND WE LIKE TO FIGURE OUT HOW WE CAN CHANGE THAT AND WE BELIEVE WHOLEHEARTEDLY THAT CHANGING THAT COMES FROM EXPLAINING HOW THIS IS A HEALTH CONDITION, HOW IT AFFECTS THE BRAIN AND HOW TREATMENT WORKS AND RECOVERY IS POSSIBLE. THANK YOU. >> THANK YOU, JESSICA. I'M GOING TO BRING THIS TO YOU. >> BEFORE I GET STARTED I WANT TO THANK DR. COLLINS, DR. TABAK, DR. KOROSHETZ, DR. VOLKOW, PORTER AND THOMAS. I HATE GOING AFTER JESSICA BECAUSE IT'S VERY EMOTIONAL BUT FIND A LOT OF SIMILARITIES IN OUR PRESENTATIONS AND WHAT OUR PATIENT POPULATIONS ARE STRUGGLING WITH. THANK YOU FOR THAT. VERY ELOQUENTLY STATED. SO-- UH-OH. THERE WE GO. I GRAPPLED WITH THIS FIRST SLIDE ABOUT TEN TIMES, I RETITLED IT BECAUSE I ASKED MYSELF WHAT EXACTLY ARE WE DEALING WITH? IT'S NOT JUST OPIOID MISUSE. IT'S NOT JUST PAIN. BUT IT'S REALLY AN EPIDEMIC OF CHRONIC ILLNESS IN OUR SOCIETY OF WHICH ADDICTION AND PAIN ARE BOTH INCLUDED. AND FOR THE MAJORITY OF PEOPLE STRUGGLING, IT'S INVISIBLE, UNLESS WE CAN HEAR THEIR WORDS OR SEE DIAGRAMS THEY WRITE DOWN IN TERMS OF WHAT THEY ARE FEELING, TRY TO DRAW, OR EXPRESS ANYTIME SOME SORT OF ARTISTIC WAY, IT'S HARD FOR ANY OF TO US LOOK AT ANY IN THIS ROOM AND IDENTIFY WHO MAY BE HAVING PAIN AND WHO DOESN'T. OUR SOCIETY IS REALLY STRUGGLING WITH A FAILURE TO UNDERSTAND WHAT PAIN IS. AND AS JESSICA SO ELOQUENTLY STATED, THIS IS LEADING TO STIGMA AND BIAS IN THESE PATIENT POPULATIONS. AND THIS MISUNDERSTANDING IS REALLY CREATING A STATE OF CONFUSION. I WAS RECENTLY REMINDED WORDS REALLY DO MATTER. LANGUAGE WE USE IN TALKING ABOUT THESE THINGS REALLY MATTERS AND CONTRIBUTE TO A LOT OF ISSUES THAT JESSICA MENTIONED. THE FIRST AND FOR MOST IS WITH PAIN. I'M NOT TALKING ABOUT WHAT'S GOING ON IN A SCIENTIFIC LEVEL BUT BOOTS ON THE GROUND, WHAT TO PEOPLE UNDERSTAND AND THINK ABOUT WHEN WE SAY THE WORD "PAIN" I CAN'T THINK OF ANYTHING ELSE IN MEDICINE WHERE THIS IS THE CASE BUT WE'RE TALKING ABOUT PAIN AS A SYMPTOM, AND A DISORDER. THAT'S CONFUSING. PEOPLE SAY, WELL, I THOUGHT PAIN IS NORMAL. WE'RE SUPPOSED TO HAVE PAIN. IT'S A NORMAL WARNING SYSTEM SO WE DON'T GO ON AND HURT OURSELVES. THAT'S TRUE. HOW DOES THAT DIFFER FROM PEOPLE WHO HAVE A PAIN DISORDER? WE NEED ACUTE PAIN AS A WARNING SIGNAL TO TELL US WHEN SOMETHING IS WRONG SO WE DON'T BURN OUR HAND ON THE STOVE BUT WE'RE TALKING ABOUT A SECONDARY PROCESS FROM UNDERLYING CONDITIONS MAYBE LIKE CANCER, AS WELL AS PAIN THAT MAY BE A NEUROLOGIC DISEASE IN AND OF ITSELF. THAT'S REALLY CONFUSING TO MOST PEOPLE. IN ADDITION, LIKE MYSELF AFTER HAVING CHRONIC PAIN FOR 30 YEARS, GETTING A NUMBER OF DIAGNOSES, AT SOME POINT WE SAY WE HAVE PAIN. IT'S AN UMBRELLA TERM FOR A LOT OF DISORDERS. SOME PEOPLE SAY THEY HAVE ARTHRITIS, IBS, I HAVE MIGRAINES, THEY ARE ALL CHRONIC PAIN CONDITIONS. ALL OF WHICH HAVE A CENTRAL COMPONENT OF PAIN DESCRIBED DIFFERENTLY, IF YOU LOOK AT DESCRIPTIVE WORDS PEOPLE USE THERE'S DOZENS OF THEM. CRAMPING, SHARP, SHOOTING, GNAWING, ELECTRIFYING, IT'S CONFUSING DEPENDING WHERE YOU EXPERIENCE PAIN, OTHER BODY SYSTEM-SPECIFIC SYMPTOMS YOU MAY HAVE. IF YOU HAVE BOWEL PAIN YOU'LL HAVE ISSUES WITH BOWEL. IF YOU HAVE JAW PAIN YOU'LL HAVE ISSUES WITH CHEWING, TALKING, SO ON AND SO FORTH AND THAT'S CONFUSING TO MOST PEOPLE AS WELL. IN ADDITION WE'RE ALL INDIVIDUALS. WE ALL EXPERIENCE PAIN VERY DIFFERENTLY. AND THERE ARE A LOT OF NON-PAIN COMORBIDITIES ASSOCIATED WITH IT. MOOD DISORDERS, SLEEP DISORDERS, FATIGUE ISSUES, COGNITION, AND SO WHEN YOU LOOK AT US WE DON'T ALL LOOK THE SAME. SOMEBODY WITH OSTEOARTHRITIS ALONE WILL NOT LOOK LIKE SOMEONE WITH DIABETIC NEUROPATHY WHO HAS DIABETES, OBESITY, MAYBE A SLEEP DISORDER WHO WON'T FUNCTION LIKE SOMETHING WITH MULTIPLE CHRONIC OVERLAPPING CONDITIONS, MOOD DISORDER, CHRONIC FATIGUE, SLEEP DISORDER, COGNITIVE IMPAIRMENT WHICH IS CONFUSING. AND ALL OF THIS MISUNDERSTANDING, LACK OF COMMUNITY THE COMMUNITY HAS LED TO STIGMATIZATION AND BIAS. IT'S PERPETUATED BY THESE TYPES OF SLOGANS, IF YOU WANT TO CALL THEM, NO PAIN NO GAIN, MIND OVER MATTER. WE HAVEN'T GOTTEN PAST THESE AND THEY SOMEHOW COMMUNICATE PAIN IS A NECESSARY THING THAT WE NEED TO EXPERIENCE IN ORDER TO GET BETTER, DO BETTER, BE BETTER IN SOCIETY. I THINK BECAUSE OF THE SOMEWHAT ADVANCE OF SCIENCE WE HAVE SOME UNDERSTANDING THIS IS A LEGITIMATE CONDITION, IT'S NOW BECOME SOMEWHAT ACCEPTABLE TO HAVE PAIN, BUT IT'S NOT ACCEPTABLE TO BE WEAK ENOUGH TO ALLOW YOURSELF TO BE IMPACTED BY IT. THE MOMENT THAT YOU SAY THAT YOU'RE UNABLE TO PARTICIPATE IN WORK OR SOCIAL ACTIVITIES OR VOLUNTEER, GO TO SCHOOL PTO MEETING, YOU'RE LABELED, YOU'RE JUDGED, AND YOU'RE MISUNDERSTOOD. IT REALLY BECOMES THIS. I AM WHAT YOU SEE. FROM WHAT YOU'RE EXPERIENCE IS, WHAT YOU THINK ABOUT PAIN, BECOMES WHO I AM. IT'S INTERESTING, RECENTLY I HEARD SOMEONE SPEAK, A PROMINENT NEUROSCIENTISTS STUDYING PAIN FOR THREE DECADES, ALSO A CLINICIAN WHO TREATED THOUSANDS OF PATIENTS. HE SAID, IT WAS NOT UNTIL HE RECENTLY HAD HIS OWN EXPERIENCE WITH CHRONIC BACK PAIN THAT HE REALLY UNDERSTOOD WHAT HIS PATIENTS WERE GOING THROUGH, WHICH WAS KIND OF MIND BLOWING THAT YOU COULD STUDY THAT, NO DISREGARD TO HIM, JUST THE FACT THIS IS SUCH A PERSONAL THING. WE HAVE SO MANY BIASES AND JUDGMENTS AND BELIEFS ABOUT THIS IN OUR SOCIETY THAT YOU REALLY DON'T UNDERSTAND UNTIL YOU EXPERIENCE IT. AT THE SAME TIME WE'RE EXPERIENCING -- PATIENTS ARE EXPERIENCING CHAOS IN THE SYSTEM, NO WORK FORCE, WE'RE NOT SURE IF WE'VE CLASSIFIED THEM CORRECTLY BY LOCATION OR BODY SYSTEM, WE HAVE A SYMPTOM BASE VERSUS MECHANISM-BASED CLASSIFICATION, LACK OF UNDERSTANDING ABOUT THESE CONDITIONS, LACK OF OBJECTIVE MEASURES, MARKERS AND DIAGNOSTICS. AND THIS HAS LED TO A NATIONAL CRISIS IN TERMS OF NUMBERS, PREVALENCE, COST, DISABILITY AND EVEN DEATHS. WHICH HAS LED TO PERSONAL CRISES FOR MILLIONS OF PEOPLE LIKE SUSAN WHO SAY TO LIVE IN PAIN IS TO LIVE IN ISOLATION. AND AT THE SAME TIME WE HAVE AN EXPLOSION OF THERAPIES OUT THERE BUT WE REALLY HAVE NO IDEA OF WHAT WORKS FOR WHOM AT WHAT COST AND AT WHAT RISK. FORMER FDA COMMISSIONER SAID UNFORTUNATELY THE FIELD OF CHRONIC PAIN TREATMENT IS STRIKINGLY DEFICIENT AND HIGH QUALITY SCIENTIFIC EVIDENCE. WHICH IS BASICALLY LEFT THE SCENARIO WHERE WE HAVE LITTLE TO NO COST-RISK/BENEFIT RATIO, AND LED CLINICIANS TO FEEL IT'S A GAME OF BLINDFOLDED DARTS WHICH MAY BE GOOD FOR PEOPLE BUILDING AT YOUR JOB BUT NOT GOOD FOR PERSONALIZED MEDICINE. A FRIEND AND COLLEAGUE WHO RUNS A MAJOR PAIN CENTER SAID WITHOUT DATA WE'RE JUST DOCS WITH OPINIONS. SO WHAT DOES PAIN RESEARCH MEAN TO PATIENTS? WE ASKED A THOUSAND PATIENTS WHAT DOES -- WHAT WORD COMES TO MIND WHEN YOU THINK OF INCREASING PAIN RESEARCH INVESTMENT? THEY SAID "HOPE." BY AND LARGE THE NUMBER ONE ANSWER WAS "HOPE." AND I RECENTLY CAME ACROSS THIS QUOTE, SOME PEOPLE CANNOT BE CURED, WHICH I THINK IS WHAT WE EXPERIENCE IN THE PAIN COMMUNITY, BUT EVERYONE CAN HEAL. WHICH IS WHY HEAL IS SO IMPORTANT, I CAN'T THINK OF A BETTER ACRONYM FOR WHAT'S NEEDED AS SCIENCE ADVANCES IN THIS FIELD AS THESE CONDITIONS ARE MORE LEGITIMIZED AND HEALING THAT NEEDS TO TAKE PLACE IN THE CHRONIC PAIN AND ADDICTION COMMUNITIES. SO WHAT ARE SOME HOPES FOR PATIENT RESEARCH AS "HEAL" ADVANCES? AS I MENTIONED WE SHALL LOOKING FOR MEASURES, MARKERS, PREDICTORS, OUTCOME MEASURES THAT ACCOUNT FOR COMPLEXITY, HOW DO WE DEFINE IMPROVEMENT, WHAT DOES THE SCORE MEAN? HOW DO WE DEVELOP MORE WELL-ROUNDED MEASURES THAT TAKE INTO ACCOUNT FUNCTION AND QUALITY OF LIFE, SLEEP, MOOD? YOU KNOW, YOU CAN GIVE SOMEONE A MEDICATION SO THE PAIN LEVEL GOES TO 1 BUT THEY MAY BE VEGETATED ON THE COUCH, IS THAT BETTER? THIS AFFECTS NEUROLOGIC AND IMMUNE SYSTEM, UNDERSTOOD BIDIRECTIONALITY IMPACT OF SLEEP AND MOOD ON PAIN AND CHRONIC DISEASE STATES. DEPARTMENT OF HEALTH AND HUMAN SERVICES HAS SAID MULTI-MORBIDITY IS NUMBER ONE HEALTH CONDITION IN THE UNITED STATES. WE ARE A POPULATION WHO HAS CHRONIC ILLNESS AND NEED TO UNDERSTAND BIDIRECTIONAL IMPACT OF THAT ON PAIN. WE NEED TRIALS THAT ACCOUNT FOR THE COMPLEXITY AND INDIVIDUALITY OF THE PAIN EXPERIENCE. I WANT TO KNOW WHAT'S GOING TO WORK FOR ME, IT'S GOING TO BE DIFFERENT THAN WHAT WORKS FOR YOU. WE NEED TRIALS THAT LOOK AT BOTH IMPACT OF COMORBID PAIN AND NON-PAIN CONDITIONS, AS WELL AS TREATMENT COMBINATIONS, VERY RARE FOR SOMEONE WITH CHRONIC PAIN TO JUST BE TAKING ONE THING ALONE. WE DON'T UNDERSTAND MAYBE SYNERGISTIC EFFECT OF PHARMACOLOGIC AND NON-PHARMACOLOGIC TREATMENT AND TRIALS THAT TAKE INTO ACCOUNT FUNCTION AND QUALITY OF LIFE, GOAL SETTING, WHAT'S IMPORTANT, WHAT I WANT TO ACCOMPLISH WITH THERAPY MAY BE DIFFERENT THAN WHAT YOU MAY WANT TO. ALSO, REVERSE TRANSLATION AND BROAD INCLUSION, INCLUDE LEARN FROM, LISTEN TO PATIENTS, INCLUDE OTHER STAKEHOLDERS EARLY AND OFTEN WHICH IS WHAT WE'RE DOING HERE TODAY. AND I THANK YOU AGAIN FOR YOUR LEADERSHIP. THAT REQUIRES MUTUAL VALUE AND RESPECT. YOU MAY HAVE SEEN THIS, PLEASE DO NOT CONFUSE YOUR GOOGLE SEARCH WITH MY MEDICAL DEGREE. A PATIENT'S RESPONSE SAID DON'T CONFUSE THE ONE HOUR LECTURE YOU GOT ON MY CONDITION WITH MY 20 YEARS OF LIVING WITH IT. RIGHT? WE ALL HAVE A ROLE TO PLAY. WE ALL HAVE A SEAT AT THE TABLE, HAVE VALUE IN TERMS OF DOING THAT. THE NUMBER ONE THING PATIENTS WANT TO SEE IS THIS CHART CHANGE. IT'S NO LONGER ACCEPTABLE FOR IT TO TAKE TWO DECADES FOR RESEARCH TO TRANSLATE INTO CARE. 17 YEARS TO TURN 14% OF RESEARCH INTO THE BENEFIT OF PATIENT CARE, WE'VE ALL SEEN THE STATISTIC. AND TO DO THAT, WE NEED TO INCLUDE ALL STAKEHOLDERS LIKE THE NIH IS DOING TODAY. TO BRIDGE THAT TRANSLATIONAL DIVIDE, TO ENSURE THAT WE'RE SUCCESSFULLY IMPLEMENTING RESERVE FINDINGS COMING OUT OF "HEAL," AND TO REDUCE THE KNOWLEDGE TRANSLATION GAP BECAUSE IT DOES TAKE A VILLAGE TO HEAL. THANK YOU. [APPLAUSE] >> THANK YOU TO JESSICA AND CHRISIN. WE'VE GOT AN IMPORTANT REMINDER WHY THE RESEARCH THROUGH "HEAL" MTTERS AND SOME VERY SPECIFIC SUGGESTIONS I HOPE WE REMEMBER DURING THE DAY'S DISCUSSION, AS WE GO THROUGH SOME OF THE MORE PARTICULAR ELEMENTS OF "HEAL" RESEARCH. SO SINCE WE'RE SCHEDULED FOR A BREAK, I THINK MAYBE WE CAN TAKE THIS. FRANCIS, WOULD YOU LIKE TO SAY ANYTHING? >> I WONDER IF THE WORKING GROUP WOULD LIKE TO COMMENT ON THESE TWO VERY POWERFUL PRESENTATIONS BEFORE WE TAKE A BREAK. WE ARE BLESSED WITH A LITTLE EXTRA TIME, AND IT WOULD BE ENTIRELY APPROPRIATE TO REFLECT A MINUTE ON WHAT WE'VE JUST HEARD. IT WAS REALLY IMPORTANT, I THINK THAT WE START OFF THIS MEETING WITH THESE PERSPECTIVES. WE'LL DIVE DEEPLY INTO ALL KINDS OF ISSUES ABOUT SPECIFIC PROJECTS INVOLVING RESEARCH, BUT WE NEED TO KEEP FOCUSED THROUGHOUT THE COURSE OF TODAY AND EVERYTHING THIS WORKING GROUP DOES ON THE REAL POINT OF THIS. THANK YOU, JESSICA AND CHRISTIN, YOU'VE GIVEN US A CLEAR REMINDER OF THAT AND HOW FAR WE HAVE TO GO TO ADDRESS THE CONCERNS OF FAMILIES AND PATIENTS. I'D BE CURIOUS IF ANYONE WOULD LIKE TO COMMENT ON THE CHARGE THIS WORKING GROUP FACES IN THE CONTEXT OF WHAT'S BEEN DESCRIBED. SO COMMENTS FROM ANYONE? WALLY? >> THE WORD THAT I HEARD THAT STUCK WITH ME THE MOST WAS "STIGMA." >> YES. >> THE PAIN COMMUNITY HAS TAKEN A SCIENTIFIC APPROACH TO FINDING TREATMENTS, AND IMPLEMENTING TREATMENTS FOR PAIN. BUT HAS NOT RECOGNIZED HOW PATIENTS ARE HIDING AND AREN'T COMING TO TREATMENT. THE ADDICTION COMMUNITY SOUNDS LIKE THEY HAVE DONE THE SAME THING. I'M NOT IN THE ADDICTION SPACE. AT LEAST NOT KNOWINGLY. BUT IT SOUNDS LIKE BOTH OF THOSE WORLDS SHARE THIS KIND OF STIGMA. I THOUGHT ABOUT SICKLE CELL DISEASE, NOT QUITE AS BAD, THEY WILL TALK TO ONE ANOTHER ON THE INTERNET. THEY WILL NOT TALK TO ME, BY THE WAY, ABOUT COMPLEMENTARY AND ALTERNATIVE MEDICINES THEY ARE USING, ABOUT ANYTHING THAT THEY ARE DOING THAT THEY WORRY I WON'T APPROVE OF, SMOKING THAT THING. AND SO TO ME, ONCE WE DO ALL THE SCIENCE, THERE'S A WHOLE OTHER IMPLEMENTATION SCIENCE PART THAT WE STILL NEED TO WORK ON, TO ACTUALLY GET PEOPLE TO COME OUT FROM HIDING, TAKE ADVANTAGE OF THE RESOURCES, TELL THEIR COMMUNITIES THAT THERE'S HELP. HAS HIV DONE IT WELL? I GUESS. BUT MAYBE WE NEED TO LEARN FROM THAT COMMUNITY AND COMMUNITIES LIKE IT, ON HOW TO GET OUR PATIENTS TO REALLY SAY DESPITE DECADES OF BEING PUT DOWN EVERY TIME I GO TO GET TREATMENT, OR COME OUT, I NOW WILL TRUST THAT I CAN GET TREATMENT AND THAT I WON'T BE STIGMATIZED. >> THANK YOU. YES, PATRICE. >> WELL, FIRST OF ALL, THANK YOU FOR MAKING SURE THAT WE HAD BOTH PRESENTATIONS TODAY. I CAN SAY THAT OFTENTIMES I'VE BEEN IN MEETINGS, WE WOULD EITHER HEAR FROM ONE OR THE OTHER, BUT NOT BOTH. I THINK THAT'S AN IMPORTANT MARKER TO PUT DOWN. I WILL SHARE MY OWN EXPERIENCE, INITIALLY TRAVELING AROUND THE COUNTRY, ON AIRPLANES, SOMEONE MIGHT LOOK AT MY MATERIALS AND SHARE A STORY ABOUT A LOVED ONE THEY LOST TO AN OVERDOSE DEATH. AND THAT WAS MY EXPERIENCE EARLY ON. NOW, WHAT I HEAR ABOUT MOST OFTEN, IF SOMEONE GLANCES AT MY MATERIALS IT'S ABOUT SOMEONE EXPERIENCING CHRONIC PAIN AND REALLY FEELING LIKE -- A WOMAN SHARED THAT SHE WAS MADE TO FEEL LIKE A CRIMINAL WHEN SHE WENT TO THE PHARMACY TO GET HER MEDICATIONS. AND SO, THOSE ARE THE STORIES THAT I'M HEARING NOW. I THINK PART OF REASON IS THAT WE REALLY DIDN'T HAVE ENOUGH OF THESE CONVERSATIONS IN CONTEXT EARLY ON IN IN THE EPIDEMIC AND NOW WE'RE EXPERIENCING SOME UNINTENDED CONSEQUENCES, AND SO IT IS VERY IMPORTANT TO HAVE THE CONVERSATIONS WITH THE LENS OR THROUGH THE LENS OF BOTH OF THESE ISSUES, AS WE LOOK AT, AGAIN, OPIOID USE DISORDER, AND CHRONIC PAIN. >> YES, CONSTANCE. >> ONE OF THE THINGS I THINK THAT'S BEEN VERY IMPORTANT IN OUR RESEARCH IN THIS AREA HAS, WHAT WE'VE LEARNED FROM PCORI, USING PATIENT AND STAKEHOLDERS, PATIENTS AND CLINICIAN AND SO FORTH. SO I AGREE WITH WHAT DR. SMITH SAID, BUT I THINK IT'S ALSO REALLY GOOD TO INVOLVE THE PATIENT PERSPECTIVE IN THE RESEARCH DESIGN IN TERMS OF THE STIGMA PIECE RATHER THAN AFTERWARDS, THAT HAS MADE A REALLY BIG DIFFERENCE IN SOME OF THE QUESTIONS WE'VE ASKED, AND HOW TO THINK ABOUT IMPLEMENTATION. SO THANK YOU. THOSE ARE REALLY GOOD IDEAS. >> I'M STRUCK BY THEMES OF MISCONCEPTIONS AND LACK OF PROVIDERS THAT ARE EVIDENCE-BASED, AND WE NEED TO FOCUS IN PART ON EDUCATING PHYSICIANS AND OTHER PRESCRIBERS, BOTH PEOPLE CURRENTLY PRACTICING AS WELL AS MEDICAL SCHOOLS, NURSING SCHOOLS, SOCIAL WORK SCHOOLS AND SO FORTH. MOST OF THE COUNTRY DOESN'T -- THERE'S HARDLY ANY ACCESS TO THESE EVIDENCE-BASED TREATMENTS, SO THAT EDUCATION OF THE CLINICIAN COMMUNITY I THINK IS REALLY VERY IMPORTANT. >> OVER HERE AND OVER HERE. >> YES, JUST TO FOLLOW UP ON WHAT MANY OTHERS HAVE SAID, I THINK THAT A LOT OF THESE FOAs ARE COOPERATIVE AGREEMENTS, THERE WEREN'T PCORI BUILD-INS, THERE MIGHT BE WAYS TO DO THAT THAT COULD BE FRUITFUL. THE OTHER THING THAT OCCURS TO ME IS THAT A LOT OF TIMES WE'RE STILL TREATING OUD AND PAIN IN THEIR SEPARATE SILOS, THERE'S SO MUCH OVERLAP BETWEEN THE TWO, WAYS WE CAN BETTER RECOGNIZE AND REALLY ADDRESS THE ADDICTIONS AND PAIN PIECE SIMULTANEOUSLY I THINK ARE IMPORTANT. >> THAT'S VERY MUCH WHAT WE WILL BE TRYING TO DO IN THE COURSE OF TODAY AS WE WILL SEEK YOUR ADVICE ON HOW TO BE SURE WE DON'T MISS THOSE AREAS OF TOUCH AND DON'T THINK THAT WE'RE TALKING ABOUT TWO SEPARATE ENTERPRISES. HEATHER? >> YEAH, ADDING ON TO THE PROVIDER EDUCATION, I THINK THERE NEEDS TO BE A PAYER EDUCATION. AND TO MAKE SURE THAT WE HAVE PRIVATE AND PUBLIC PAYERS AT THE TABLE BEING PART OF THE SOLUTION, BECAUSE WHEN I KNOW WHEN I GO TO TRY TO IMPLEMENT EVIDENCE-BASED PRACTICE, INTO THE CLINIC THAT I HAVE, THE FIRST THING WE RUN INTO, THERE'S NO CODE FOR THAT. THE REIMBURSEMENT IS TOO LOW. HOW DO YOU EN IMPLEMENT? THINGS WE NEED TO DO. AND THE OTHER THING I HEARD FROM OUR POWERFUL PRESENTATIONS WAS A WORD YOU DIDN'T SAY, WHICH IS "DISCRIMINATION." I HEARD STIGMA BUT NOT DISCRIMINATION, AND I THINK THAT UNFORTUNATELY IS ALIVE AND WELL AND TO BRING THAT TO THE LIGHT TO HELP ERADICATE IT IN MULTIPLE WAYS. THANK YOU. >> POINT TAKEN. YES? >> WHAT REALLY STRUCK ME WAS THE URGENCY FOR TRANSLATION. THIS WORK NEEDS TO GET OUT FAST. IT'S NOT GETTING OUT FAST ENOUGH. AND I KNOW WE'RE ALL HERE WORKING TOWARDS ADVANCING NEW DISCOVERIES, BUT EVEN THE DISCOVERIES WE'VE ALREADY MADE WHICH WE KNOW FROM DATA ARE PROMISING OR EFFICACIOUS ARE NOT GETTING OUT. SO I THINK WE NEED TO HOLD THAT IN THE FOREFRONT OF OUR MIND. I KNOW THAT THE FOAs AND RFAs ARE REALLY ORIENTED TOWARDS RAPID TRANSLATION, AND I THINK THAT'S WISE, BECAUSE PEOPLE NEED IT FASTER. >> AGREED. YES? >> SO, I'M INTERESTED TO KNOW WHAT -- THANK YOU BOTH FOR YOUR POWERFUL PRESENTATIONS BUT I'M INTERESTED TO KNOW HOW YOU'RE DEVELOPING YOUR MATERIALS TO SHARE WITH YOUR RESPECTIVE CLIENTS WHO COME TO YOU BECAUSE I THINK PROVIDERS NEED TO SO THESE AS WELL BECAUSE EDUCATING PROVIDERS ON NEUROSCIENCE IS AN UPHILL CLIMB, WE NEED TO DO IT IN SCHOOLS, PROGRAMS, ACCREDITING BODIES AS WELL FOR EACH OF THOSE PROGRAMS, AND THAT'S A CHALLENGE AS WELL BECAUSE IF THAT GOES IN, SOMETHING ELSE HAS TO COME OUT OF THE PACKED CURRICULA. BUT I THINK THE PATIENT-CLIENT EDUCATION PIECE IS SO CRITICAL. AND IN ADDITION TO INSURANCE OR PAYERS, WE ALSO NEED TO THINK ABOUT EMPLOYERS. SO IN THE LOW BACK PAIN WORLD WHERE PEOPLE ARE ON WORKERS' COMPENSATION THEY ARE OFTEN STIGMATIZED AS WELL, AND THEIR CO-WORKERS, MANAGER, SUPERVISOR, UP THE CHAIN, CAN ALSO HAVE A HUGE INFLUENCE ON HOW THEY ARE STIGMATIZED. SO I DON'T KNOW WHERE WE ARE WITH DEVELOPING PARTNERSHIPS AND THINKING BROADLY BUT THOUGHT I WOULD PUT THOSE ON THE TABLE AS WELL. >> POINT TAKEN. >> JESSICA? >> IN TERMS OF THE FOCUS GROUPING OR TESTING, INFORMATION FOR THE PATIENT SIDE AND FAMILY SIDE, THERE'S USUALLY A REALLY WORRIED MOM OR DAD EARLY ON, IN THE DEVELOPMENT OF A SUBSTANCE USE DISORDER, WHO IS AT THE HELM TRYING TO FIGURE OUT WHERE TO GO AND WHAT TO DO, SOMETIMES ON A SIBLING, SPOUSE OR PARTNER, BUT WHEN WE STARTED THIS I THOUGHT, GREAT, WE'RE GOING TO BUILD THIS, YOU KNOW, VIDEO EXPLAINER, BOOKLET, PAMPHLET, WE'RE GOING TO GET IT OUT IN A FEW WEEKS. BUT THE REALITY OF WHAT WE FOUND, IT'S NOT JUST A DIFFERENCE IN TRYING TO EXPLAIN NEUROSCIENCE OR COMPLICATED SCIENCE PIECES BUT OUR FAMILIES WHEN THEY ARE LOOKING FOR THIS INFORMATION ARE IN CRISIS. SO THEY THEMSELVES ARE PATIENTS IN A WAY, AND SO THEY ARE LIKE LIMBICALLY ENGAGED, SO I THINK LEARNING CHANGES, RIGHT? YOU'RE NOT NECESSARILY WORKING FROM THE RIGHT SIDE OF YOUR BRAIN AND IN A CALM STATE OF MIND, LOOKING AT THE MINDFULNESS GUY DOWN HEAR, IT'S IMPORTANT. INSTEAD OF THE FIRST PIECE OF INFORMATION WE PUT OUT WHEN WE STARTED ABOUT EXPLAININGED BRAIN SCIENCE, INSTEAD OF TAKING NINE DAYS OR -- IT TOOK NINE MONTHS TO GET IT RIGHT. WE FOCUS GROUP WITH FAMILIES IF IT'S FAMILY FOCUS. IF IT'S PATIENT FOCUS WE HAVE A SEPARATE GROUP, ACTIVE USE DISORDER, DIFFERENT CATEGORIES IN THOSE WITH ACTIVE USE DISORDER. LANGUAGE YOU USE REALLY MATTERS, PARTICULARLY ON SORT OF WHERE ARE YOU IN YOUR DISEASE PROGRESSION. AND YOU NEED TO HAVE SMALLER PACKETS OF INFORMATION INSTEAD OF OVERWHELMING PEOPLE. WE'VE STARTED TO TRY TO TRANSLATE SOME TO PROVIDERS, SO WE WELCOME FEEDBACK FROM THE HEAL INITIATIVE AND ANYONE THAT'S ON THIS WORKING GROUP. BECAUSE I DO THINK THIS INFORMATION NEEDS TO BE PROVIDED TO OTHERS AS WELL. IT IS A REALLY HIGH PRIORITY FOR US. THANKS FOR ASKING THE QUESTION BECAUSE MAKING SURE YOU GET IT RIGHT, THAT IT'S ACTUALLY -- THE INFORMATION IS CONSUMED AND UNDERSTOOD IS A LITTLE BIT MORE OF A SENSITIVE AND TIME-CONSUMING PROCESS THAN WE INITIALLY ASSUMED. >> SO, I WOULD BE ALSO INTERESTED TO KNOW IF EITHER ONE OF YOU ARE WORKING ON MATERIALS FOR PATIENTS OR CLIENTS FROM LOW-RESOURCE SETTINGS OR LOW SOCIOECONOMIC STRATA AS WELL, BECAUSE THE PATIENT EDUCATION MATERIALS I'VE SEEN FOR PARTICULARLY CHRONIC PAIN EDUCATION AND PAIN NEUROSCIENCE, THEY ARE ABOVE AN EIGHTH GRADE LEVEL, AND, AGAIN, TO THE POINT OF INCLUSION, WE NEED TO THINK ABOUT THAT. AND I CAN'T EMPHASIZE ENOUGH IN MY EXPERIENCE OF FOLLOWING PEOPLE WITH CHRONIC PAIN, THE NUMBER OF PEOPLE THAT THEY TOUCH IN THEIR JOURNEY WHO CONTRIBUTE TO THEIR PAIN-RELATED DISABILITY IS ENORMOUS. IT'S THE SPOUSE, PARTNER, FRIENDS AND SO FORTH. SO THE OTHER THING TO ADD IS THE P.R. CAMPAIGN. >> YEAH, I WOULD DEFINITELY AGREE. ONE THING I WAS GOING TO SAY OF COURSE WHEN WE DEVELOP OUR MATERIALS DEVELOP THEM WITH PATIENTS, CLINICIANS, SCIENTIFIC ADVISORY BOARD. BUT THE ISSUE IS THAT THE VERY -- THIS IS ACROSS THE BOARD FOR DISEASE ADVOCACY IN GENERAL, THE PERCENTAGE OF PEOPLE THAT ARE ASSOCIATED WITH ANY NON-PROFIT ORGANIZATION OR ADVOCACY MOVEMENT IS SMALL COMPARED TO THE POPULATION YOU'RE DEALING WITH. WITH PAIN IN PARTICULAR, IT'S CHALLENGING BECAUSE THERE'S DIFFERENT POPULATIONS. SO IN THE CHRONIC PAIN POPULATION, THE MESSAGE IS MORE ABOUT LEARNING TO LIVE WITH PAIN AND UNDERSTANDING THAT IT'S NOT A WARNING SIGNAL FOR SOMETHING, A TUMOR, CANCER OR SOMETHING THAT MAY BE GOING ON BUT IN A GENERAL INITIAL CONSULT WITH PEOPLE WHO JUST DEVELOP PAIN, THAT IS -- YOU CAN'T USE THAT MESSAGE BECAUSE THAT'S -- SO THERE'S DIFFERENT MESSAGING FOR DIFFERENT POPULATIONS. AND IT'S CHALLENGING TO GET THEM ACROSS THE BOARD TO THOSE GROUPS. BUT I COMPLETELY AGREE WITH YOU, WE DEVELOPED CONTINUING MEDICAL EDUCATION PROGRAM FOR PRIMARY CARE PROVIDERS, FIRST LINE PROVIDERS, ALONG WITH PATIENT EDUCATION PIECE SO THERE'S BEEN A LOT OF MATERIALS THAT HAVE BEEN DEVELOPED BUT GETTING THEM OUT INTO THE GRAND PUBLIC, ESPECIALLY WHEN IT COMES TO PAIN, ESPECIALLY WHEN IT COMES TO STIGMATIZED DISORDERS CAN BE VERY CHALLENGING SO I AGREE DEFINITELY A PUBLIC RELATIONS AND MASS MEDIA TYPE CAMPAIGN IS WHAT'S NEEDED IN THE AREA. >> SO, I DO THINK WE HAVE TO DEVELOP MATERIALS FOR LOW RESOURCE OR IN CRISIS PATIENTS AND FAMILY -- SORT OF KIND OF POCKETS OF OUR -- THEY ARE VERY DIFFERENT BACKGROUNDS, EVEN THOSE WITH HIGHER EDUCATION LEVEL ARE IN CRISIS SO THEY CAN'T TAKE THE SAME AMOUNT OF INFORMATION TO CONSUME AT ONCE ANYWAY, SO WE HAVE TARGETED TO HAVE ALL PATIENT AND FAMILY MATERIALS DEVELOPMENT AT A FOURTH GRADE LEVEL, AND IT'S NOT JUST FOURTH GRADE LEVEL. WE'VE FOUND CERTAIN WORDS OR TERMS WILL SHUT A PATIENT OR FAMILY MEMBER DOWN. I CAN'T SAY THE WORD "RECEPTOR." I LOSE THEM. THEY ARE GONE IN A SECOND. I CAN'T GET INTO CERTAIN NITTY-GRITTIES BECAUSE I'M DONE. THEY ARE NOW SORT OF IN THAT MOMENT OF FEELING OVERWHELMED AND NOT KNOWING WHERE TO GO. WHEN YOU GIVE THEM INFORMATION THAT FEELS LIKE IT'S A BRICK WALL, I'VE LOST MY ABILITY TO EDUCATE. MAKING SURE IT'S NUANCED, YOU TAKE THE TIME TO HOLD THE HANDS AND SEE WHAT WORKS. I'M WORKING ON MY NEXT CARTOON WITH NORA, WHICH WILL BE REALLY EXCITING. WE'RE DOING ONE ON THE 28-DAY MYTH. WE DID A SERIES ON THE MYTHS LAST YEAR. WE HAVE FOUND THESE -- IT SEEMS OVERLY SIMPLISTIC BUT THE CARTOON OR WHITE BOARD EXPLAINERS HELP BREAK DOWN COMPLICATED INFORMATION AND MAKE IT FEEL REACHABLE. HOWEVER, THE WORDS WE USE AND TERMS THAT WE CAN TACKLE ARE STILL LIMITED, EVEN IN THAT FORMAT. AND WE'VE ALSO FOUND THOUGH THAT AS WE BOIL THIS DOWN, SOMETIMES WE BOIL TOO FAR DOWN TO BE ABLE TO USE THIS WITH OUR PROVIDER COMMUNITY. SO HOW DO WE MAKE SURE, LIKE THE DOCS AND NURSES WE'RE WORKING WITH DON'T WANT TO WATCH CARTOONS, TRYING TO FIGURE OUT -- NEITHER DO LAW ENFORCEMENT. AND CRIMINAL JUSTICE PROFESSIONALS, BY THE WAY. IN NUANCING, TAILORING THIS INFORMATION, I THINK OUR PATIENT AND FAMILY PIECES ARE GOING TO BE STAND-ALONE AND THEN IT NEEDS TO BE A PRIORITY TO MAKE SURE OTHER STAKEHOLDERS HAVE ACCESS TO THAT INFORMATION, BUT MAYBE IN A DIFFERENT FORMAT. I'D LOVE TO SHARE WITH YOU SOME OF THE STUFF. >> ADD ONE MORE THING, THE OTHER CHALLENGE IS WHAT DR. JONES MENTIONED, IS THAT THE RESOURCES THAT ARE AVAILABLE IN CLINICAL CARE RIGHT NOW, WE MAKE RECOMMENDATIONS ABOUT MULTI-DISCIPLINARY TEAM-BASED MEDICAL CARE BECAUSE WE KNOW THAT'S, YOU KNOW, WHAT WORKS FOR PATIENTS WITH CHRONIC PAIN. THE PROBLEM IS THAT THERE IS AN INSUFFICIENT WORKFORCE. WE DON'T HAVE THE PROVIDERS THAT WE NEED. WE DON'T HAVE THE SYSTEM SET UP, DON'T HAVE REIMBURSEMENT POLICIES AND PRACTICES IN PLACE. SO YOU CAN ONLY GO SO FAR ON WHAT YOU'RE RECOMMENDING AND TO PATIENTS TO, YOU KNOW, WHAT THEY CAN ACTUALLY ACT ON OR DO WITH THE CURRENT HEALTHCARE SYSTEM SETTING THE WAY IT IS. IT'S A MAJOR CHALLENGE. >> VERY GOOD POINT. IT'S BEEN A VERY IMPORTANT AND RICH DISCUSSION. I'M GLAD WE HAD TIME TO HEAR FROM ALL OF YOU AND TO REFLECT ON WHAT WE HEARD FROM JESSICA AND CHRISTIN'S REALLY THOUGHTFUL AND SOBERING PRESENTATION. IT GIVES US ALL KINDS OF REASONS TO ROLL UP OUR SLEEVES AND SEE WHAT WE CAN DO TO TRY TO ADDRESS THOSE ISSUES. LET'S TAKE A 10-MINUTE BREAK, AND WE'LL RECONVENE AT TEN MINUTES OF 10:00, AND GET BACK ONTO THE AGENDA WHICH MEANS WE START TO GET INTO THE NITTY-GRITTY OF WHAT THESE RESEARCH OPPORTUNITIES MIGHT LOOK LIKE AND HELP WE NEED FROM ALL OF YOU. WE'LL RECONVENE IN TEN MINUTES. I WOULD LIKE TO MOVE US INTO THE OVERVIEW OF "HEAL," THIS HELPING TO END ADDICTION LONG-TERM. I HOPE YOU LIKE YOUR VISUAL, BY THE WAY. YOU HAVE NO IDEA HOW MUCH TIME WENT INTO TRYING TO FIGURE OUT EXACTLY WHAT WE COULD COME UP WITH THAT WOULD NOT MAKE PEOPLE CRINGE AND MAKE SOME PEOPLE SMILE. YOU CAN SAY THE IMAGES IN THE BACKGROUND, PEOPLE IN VARIOUS SETTINGS, WHICH SUGGEST WHERE WE'RE TRYING TO DO AND THE WAY THE WORD IS PUT FORWARD WITH THE HANDS REACHING OUT TO HELP EACH OTHER, CLEARLY WHAT WE HAVE TO DO TO ACCOMPLISH WHERE WE NEED TO GO. I'M GOING TO GIVE AN OVERVIEW FROM THE TOP LEVEL WHAT THIS INITIATIVE LOOKS LIKE. NORA AND WALTER WILL DRILL DOWN INTO THE COMPLEX INITIATIVES. BECAUSE OF THE COMPLEXITY WE'RE NOT GOING TO ASK ALL OF YOU TO COMMENT ON EVERYTHING, THERE WOULDN'T BE TIME IF WE KEPT YOU HERE FOR WEEKS BUT WE WANT TO GET A SENSE OF THE LANDSCAPE, AND THEN AFTER WE HAVE THAT OVERALL LANDSCAPE WE WILL BE DRILLING DOWN INTO FIVE SPECIFIC INITIATIVES WHERE WE DO THINK GETTING SOME INPUT FROM YOU IS GOING TO BE HELPFUL AS WE TRY TO BALANCE THIS PROGRAM APPROPRIATELY TO TACKLE THE VERY LARGE LIST OF OBJECTIVES WE'RE TRYING TO ACHIEVE. DON'T BE ALARMED IF IT SEEMS OVERWHELMING IN THE BIG LANDSCAPE PICTURE. AGAIN, WE WILL TRY TO GET INTO MORE AND SPEAK YOUR EXPERIENCE. WE'LL NEED MORE INPUT FROM YOU TO START TO HELP US THINK ABOUT THIS. I DON'T HAVE TO TELL THIS AUDIENCE HOW SEVERE THIS CRISIS IS, HOWEVER YOU CHOOSE TO DISPLAY THE FACTS, COMPARING 1999 TO 2016 BREATHTAKING CHANGES WITH HOT SPOTS IN CERTAIN AREAS LIKE THE APPALACHIAN AREA AND THE SOUTHWEST, BUT THERE'S NO PART OF THE COUNTRY NOT TOUCHED BY WHAT'S HAPPENING. IN 2017, 70,000+ OVERDOSE DEATHS, MAJORITY FROM OPIOIDS, AND GOING UP. THERE MAY BE SOME SUGGESTION THAT THIS LEVELED OFF, CDC SUGGESTS WE MAY HAVE HIT THE HIGHEST, BUT THAT'S WAY TOO HIGH. NOT MUCH TO CELEBRATE BUT SOMETHING TO POINT TO WE'RE STARTING TO SEE IMPACT OF THINGS DONE BUT MUCH MORE REMAINS. WHAT IS "HEAL"? WE BELIEVE THAT SCIENCE HAS A LOT TO CONTRIBUTE TO THIS NATIONAL PUBLIC HEALTH CRISISEL. WE WANT TO BRING THE BEST STRATEGIES AS WELL AS ENHANCING PAIN MANAGEMENT FOR PEOPLE WITH CHRONIC PAIN. SO, THOSE ARE BOTH INCLUDED WITHIN THIS ENTERPRISE WHICH HAS INVOLVED VAST NUMBER OF HOURS AND LOTS AND LOTS OF SENIOR LEADERS AND PEOPLE ALL THE WAY ACROSS THE COUNTRY HELPING US THINK THROUGH WHAT THIS MIGHT LOOK LIKE IN TERMS OF ALL-HAND-ON-DECK EFFORT TO BRING SCIENCE TO BEAR ON THE CHALLENGE. THE GOALS ARE SCIENTIFIC SOLUTIONS TO THE OPIOID CRISIS. WE'RE COORDINATING WITH THE HHS SECRETARY, ALEX AZAR IS INCREDIBLY FOCUSED, AS BRETT GIREAX WHO SPENT HALF HIS TIME AT HHS FOCUSED ON THIS. THE SURGEON GENERAL, JEROME ADAMS, COUNTLESS HOURS EVERY WEEK IN COMMUNITIES SPREADING THE WORD ABOUT THE NEED TO INTERVENE. OTHER PARTNERS AND OFFICIALS AND COMMUNITIES, THIS HAS TO BE LINKED IN AN EFFECTIVE WAY. SO, WHAT WE HAVE IN TERMS OF RESOURCES IS VERY SUBSTANTIAL. THAT'S TO BE POINTED OUT TO AND WE NEED TO RECOGNIZE THE CONGRESS OF THE UNITED STATES SAW THIS AS A VERY HIGH PRIORITY. JUST A LITTLE LESS THAN A YEAR AGO PART OF THE CONGRESSIONAL DELIBERATIONS ABOUT THE FISCAL YEAR 18 BUDGET WHICH YOU KNOW IT WAS LATE BECAUSE OF OTHER MANEUVERS, BUT AT THAT POINT WE DID LEARN THAT WE WERE GOING TO BE GIVEN A $500 MILLION ALLOCATION FOR ADDRESSING THE OPIOID AND CHRONIC PAIN CRISIS, AN ALLOCATION THAT'S NOT JUST FOR ONE YEAR. IT GOES INTO THE BASE FUNDING, SO AT LEAST UNTIL THEY CHANGE THEIR MINDS, WE HAVE HALF A BILLION DOLLARS SPECIFICALLY DEVOTED TO THIS EFFORT. TO ADD TO WHAT WE'VE ALREADY BEEN SPENDING. WHEN THAT CONSIDERS ROUGHLY $600 MILLION THAT WAS BEING SPENTED A NIDA FOR OPIOID CRISIS AND MORE UNDERSTANDING PAIN THIS IS STILL A BIG INCREMENT AND SPECIFICALLY TARGETED INCREMENT THAT WE WELCOMED. I SHOULD TELL YOU GOVERNMENT BUDGETARY MINUTIA, WHEN YOU GET MONEY FROM THE CONGRESS YOU HAVE TO SPEND IT BY OCTOBER 1 OR IT GOES AWAY. RECOGNIZING THAT THEY DIDN'T COME UP WITH THIS UNTIL HALFWAY THROUGH THE YEAR, THEY DID SAY WE COULD CARRY OVER SOME OF THOSE FUNDS IN FY19, AND OF COURSE IN FY19 WE GOT ANOTHER $500 MILLION, AS I SAID THIS IS IN THE BASE. THAT'S WHERE THE $850 MILLION COMES FROM. $350 MILLION WAS FROM FY 18 WE DID NOT SPEND BY OCTOBER 1, BECAUSE WE WANTED TO SPEND IT WISELY, THE REST IN FY19 ALLOCATION. THAT'S A SUBSTANTIAL AMOUNT OF FUNDS THAT WE'RE NOW SEEKING TO PUT INTO THE PROGRAMS THAT WE'RE GOING TO TALK TO YOU ABOUT. AND THIS WAS A VERY ALL-HAND-ON-DECK EFFORT AT NIH TO TRY TO IDENTIFY IN THE SITUATIN WHAT ARE THE SCIENCE OPPORTUNITIES THAT WE MIGHT OTHERWISE NOT HAVE TRIED TO TACKLE. LARRY TABAK LED THE EFFORT THAT BROUGHT TOGETHER VIRTUALLY EVERY INSTITUTE TO SEE WHAT IDEAS THEY HAD TO CONTRIBUTE THIS. WE ENDED UP WITH 12 INSTITUTES AND CENTERS LEADING 26 "HEAL" RESEARCH PROJECTS, INVOLVING AS COLLABORATIONS OVER 20 INSTITUTES, CENTERS AND OFFICES. THIS COVERS THE GAMUT FROM PREVENTION RESEARCH, BASIC AND TRANSLATIONAL RESEARCH, CLINICAL TRIALS AND ALL THE WAY TO IMPLEMENTATION SCIENCE, MULTIPLE THINGS SUCH AS CRIMINAL JUSTICE, HEALTH CARE, ET CETERA, RESULTING IN RELEASE WHICH WAS QUITE A BIT OF WORK TO PUT TOGETHER MORE THAN 40 FUNDING ANNOUNCEMENTS FOR FY19 THAT ARE THE STREETS, SOME HAVE NOW ALREADY RESULTED IN DEADLINES AND APPLICATIONS AND REVIEWS, MANY OF WHICH WILL BE COMING ALONG IN THE NEXT FEW MONTHS FOR DECISION MAKING ABOUT HOW TO SPEND THE FUNDS. LET ME TRY TO DESCRIBE EVEN THOUGH IT'S 40 PROJECTS IN A WAY THAT WILL MAKE SENSE HOW THIS FITS TOGETHER. I APPRECIATED COMMENTS THAT WE NEED TO REMEMBER WHAT WE'RE TRYING TO DO ABOUT ENHANCING PAIN MANAGEMENT FOR 25 MILLION PEOPLE WITH CHRONIC PAIN EVERY DAY IS CONNECTED WITH TREATMENTS AND PREVENTION FOR MISUSE AND ADDICTION. IT'S ONE BIG CIRCLE BUT ATTACHED IN A WAY WE'VE TRIED TO ORGANIZE 40+ PROJECTS, SIX THEMES THAT PULL TOGETHER SOME OF THESE AREAS. AGAIN, UNDERNEATH THIS DIAGRAM THAT YOU SEE HERE IS MUCH LONGER LIST OF SPECIFIC PROJECTS. LET ME JUST TRY TO WALK YOU THROUGH, AGAIN, IN A PRETTY SUPERFICIAL LEVEL BUT HOPEFULLY TO GIVE A SENSE OF THE LANDSCAPE WHAT'S UNDERNEATH EACH SUBBULLET, EXPAND THERAPEUTIC OPTION AT 9:00 ON THE CLOCK, WE'LL MOVE AROUND THIS CIRCLE IN COUNTERCLOCKWISE FASHION AND SAY A LITTLE BIT ABOUT WHAT IS UNDERNEATH EACH OF THOSE. SO EXPANDING THERAPEUTIC OPTIONS, WELL, WE NEED NEW MORE USER FRIENDLY FORMULATIONS OF EXISTING MEDICATIONS. AGAIN NORA WILL TALK MUCH MORE IN DETAIL ABOUT SOME OF THE SCIENCE UNDERNEATH HERE THAT WE'RE SEEKING TO TRY TO INSPIRE. LONGER DURATION, MORE POWERFUL OVERDOSE REVERSERS, TO REDUCE RESPIRATORY DEPRESSION, IMMUNOTHERAPIES, VACCINES TO PREVENT RELAPSE AND OVERDOSE, WHICH WORK HAS BEEN DOWN BUT WE NEED TO PUSH THAT FORWARD. AND NEW TARGETS, NEW APPROACHES FOR TREATING OPIOID USE DISORDER. ALL OF THOSE WORDS THAT YOU SEE THERE REPRESENT SIGNIFICANT RESEARCH PROJECTS NOW IN THE PHASE OF SEEKING OPPORTUNITIES TO FUND RESEARCHERS TO DO MORE OF THIS. I THINK WHAT JESSICA SAID EARLIER ABOUT THE IMPORTANCE OF BEING ABLE TO OFFER TO INDIVIDUALS WAYS TO HELP THEM THAT IS NOT ONE-SIZE-FITS-ALL IS A LOT OF WHAT WE'RE TRYING TO DO HERE BECAUSE PEOPLE ARE DIFFERENT AND PEOPLE NEED DIFFERENT APPROACHES TO ASSIST THEM. THE NEXT THEME, DEVELOPING NEW AND IMPROVED PREVENTION AND TREATMENT STRATEGIES, WE ARE CONCERNED ABOUT HOW ADOLESCENTS TRANSITION INTO OPIOID USE DISORDER, AFTER EXPERIMENTATION, HOW DO WE PREVENT THAT. WE NEED TO UNDERSTAND THE ROLE OF SLEEP DYSFUNCTION. IT'S VERY MUCH IN THERE. IN THE DISORDER AND THE RECOVERY. WE TALK ABOUT PEOPLE WHO ARE CLEARLY FALLING INTO ADDICTION ZONE BUT WHAT ABOUT PEOPLE WHO AREN'T QUITE IN THAT PLACE? BUT ARE GOING THROUGH MISUSE, LOW SEVERITY DISORDERS, MAY BE AT RISK FOR GETTING FURTHER DOWN THAT PATH, WE HAVEN'T DONE A LOT TO TRY TO FIGURE OUT WHAT THOSE INTERVENTIONS OUGHT TO BE. HERE IS A BIG ONE. HOW LONG SHOULD MEDICATION TREATMENT FOR OUD BE SUSTAINED? I KEEP ASKING NORA THESE QUESTIONS, AND THE ANSWER USUALLY IS WE DON'T REALLY HAVE RIGOROUS DATA TO KNOW. AGAIN, IT'S PROBABLY DIFFERENT FROM PERSON TO PERSON. MY GOSH, IF WE HAVE 2 MILLION PEOPLE AND DON'T EVEN KNOW HOW TO RECOMMEND TO THEM HOW LONG THEY NEED TO BE IN TREATMENT, WE REALLY HAVE A BIG EVIDENCE GAP. IT'S MORE THAN 28 DAYS, CERTAINLY. IT'S PROBABLY A LOT MORE THAN THAT. WE NEED A BETTER UNDERSTANDING HOW THAT WORKS. COLLABORATIVE CARE FOR PEOPLE WITH COMMON MENTAL DISORDERS, ESTIMATES ARE 40% OF PEOPLE WITH OPIOID USE DISORDER HAVE A DIAGNOSEABLE MENTAL DISORDER, AND WE HAVE NOT DONE ENOUGH TO UNDERSTAND THE INTERSECTIONS THERE. THE NEXT THEME IS MORE ABOUT OPTIMIZING EFFECTIVE TEAMS, HOW DO WE ENHANCE THE CLINICAL TRIALS NETWORK WHICH WE'RE GLAD IS THERE TO ADDRESS OPIOIDS. A BIG ISSUE ABOUT CRIMINAL JUSTICE SYSTEM, OUGHT TO BE AN OPPORTUNITY FOR INTERVENTIONS, MANY PEOPLE WITH OPIOID USE DISORDER END UP INTERACTING WITH THE CRIMINAL JUSTICE SYSTEM, THAT'S AN INTERVENTION MOMENT. IT DOESN'T ALWAYS GET UTILIZED THAT WAY. UNDERSTANDING THE ROLE OF BEHAVIORAL HEALTH INTERVENTIONS, YOU'LL HEAR ABOUT BRIM, WHAT COULD WE BE DOING IN ADDITION TO MEDICATION, THAT WOULD MAKE THESE PROGRAMS EVEN MORE EFFECTIVE. THERE'S A LOT OF ANECDOTAL DATA, THERE'S NOT NEARLY AS MUCH IN THE WAY OF RIGOR. AND THEN A BIG ONE THAT WE ARE EXCITED ABOUT AND ALSO VERY MUCH IN THE MIDST RIGHT NOW OF REVIEWING, THERE ARE SITE VISITS GOING ON THIS WEEK, NEXT WEEK. >> NEXT WEEK. >> NEXT WEEK. THE IDEA HERE IS IF YOU REALLY WANT TO SAY YOU'RE PUTTING EVERY KNOWN POTENTIAL INTERVENTION TOGETHER IN A COMMUNITY WHAT WOULD THAT LOOK LIKE, PRIMARY CARE DOC, EMERGENCY ROOM, CRIMINAL JUSTICE SYSTEM, POLICE, EMTS, STATE HEALTH DEPARTMENT FOCUSED IN A SPECIFIC GEOGRAPHIC AREA WORKING TOGETHER, WHAT COULD YOU ACCOMPLISH? WE'VE DONE A LOT OF, WELL, LET'S TRY THIS OR THAT. LET'S TRY IT ALL AT ONCE AND SEE WHAT MIGHT HAPPEN. THAT'S CALLED THE HEALING COMMUNITY STUDY, AND THAT REVIEW OF VERY SIGNIFICANT NUMBER OF GEOGRAPHIC AREAS THAT APPLIED IS UNDERWAY NOW BOTH AS PAPER REVIEW AND SERIES OF SITE VISITS AND HOPE TO BE ABLE TO MAKE DECISIONS BY APRIL ABOUT WHICH COMMUNITIES ARE GOING TO GET THOSE FUNDS. THIS IS GOING TO BE SOMETHING WE HOPE WILL BE REALLY PROFOUNDLY IMPORTANT AND EXTRAPOLATED TO THE REST OF THE COUNTRY. THEN THERE'S THIS HEARTBREAKING SITUATION HOW BEST TO MANAGE NEWBORNS WITH NEONATAL OPIOID WITHDRAW SYSTEM, NAS OR NOWS, YOUR FAVORITE WAY OF DESCRIBING. I THINK IT'S OPIOID WITH WITHDRAWAL SYNDROME, TO FIGURE OUT NOT ONLY ACUTE WAY TO BEST MANAGE THAT CIRCUMSTANCE FOR THOSE BABIES WHO ARE, AS YOU KNOW, FOUND IN EVERY NEONATAL ICU THESE DAYS. BUT ALSO WHAT'S THE LONG-TERM CONSEQUENCE? WE KNOW FAR TOO LITTLE ABOUT THAT. IT'S A HARD QUESTION TO ASK BECAUSE OF ALL KINDS OF OTHER ENVIRONMENTAL AND SOCIAL CIRCUMSTANCES THAT ARE LIKELY TO BE INVOLVED IF PARENTS SUFFERED FROM OPIOID ADDICTION, WHAT HAPPENS TO THE CHILD'S FAMILY ENVIRONMENT, SO THAT'S ANOTHER STUDY, THE HEALTHY BRAIN AND COGNITIVE DEVELOPMENT STUDY, BCD. WE GOT AROUND THE CURVE IN TERMS OF THE GREEN ZONE, NOW WE'RE GOING TO THE BLUE ZONE, ENHANCING PAIN MANAGEMENT, RECOGNIZING THE OVERLAPS HERE. THE PAIN MANAGEMENT, YOU'LL HEAR MORE ABOUT THIS PART FROM WALTER IN A LITTLE BIT, WE NEED AN OPPORTUNITY TO UNDERSTAND ORIGINS OF CHRONIC PAIN. THERE'S A COMMON FUND PROJECT ALREADY UNDERWAY WHICH WAS NOT SPECIFICALLY PART OF THE HEAL INITIATIVE, BUT SO NICELY LINKED WE THINK OF IT THAT WAY, TRYING TO UNDERSTAND WHAT HAPPENS IN THAT TRANSITION FROM ACUTE TO CHRONIC PAIN. WHY IS IT THAT SOME PEOPLE WHO HAD A KNEE REPLACEMENT SEVERAL MONTHS LATER WOULD TELL YOU THEY ARE DOING WELL, AND OTHERS END UP IN A CHRONIC PAIN SITUATION THAT'S HARD TO BREAK, WHAT HAPPENS? WHAT'S THE SIGNATURE? WHAT CAN WE DO TO BLOCK THAT TRANSITION? ONCE IT HAPPENS IT'S HARD TO TAKE IT BACK. WE NEED MORE TARGETS FOR SAFE AND EFFECTIVE PAIN TREATMENT AND TO PURSUE THOSE WITH APPROPRIATE THERAPEUTIC DEVELOPMENTS. WE NEED TO ENGINEER PRE-CLINICAL SCREENING PLATFORMS IN ORDER TO ASSIST TO IDENTIFY TARGETS WE DON'T KNOW ABOUT YET AND HOW BEST TO PUT THAT INTO PLACE IN TERMS OF COMING UP WITH THERAPEUTICS THAT WORK. AND THEN TRANSLATE ALL OF THAT, NOT JUST FOR DRUGS BUT INTO DEVICES FOR PAIN TREATMENT WHICH IS ALSO SIGNIFICANT PART OF "HEAL"'S INTERESTS, AND WE HAVE I THINK AS A RESULT OF THAT TRIED TO INTEGRATE INTO ANYTHING AS FAR AS INTERVENTION NOT JUST DRUGS, NOT JUST DEVICES BUT ALSO NON-PHARMACOLOGICAL AND NON-DEVICE APPROACHES INVOLVING COMPLEMENTARY INTEGRATIVE HEALTH. IN TERMS OF HOW WE'RE GOING TO ADVANCE THESE TREATMENTS THROUGH CLINICAL RESEARCH, YOU ARE GOING TO HEAR ABOUT EPPIC-Net, A CLINICAL NETWORK SET UP TO TEST OUT THESE NOVEL TREATMENTS IN A NEW NETWORK. YOU'LL HEAR A LITTLE BIT ABOUT THE BACK PAIN RESEARCH CONSORTIUM, BACPAC. AND THEN TRYING TO FIGURE OUT HOW BEST TO ESTABLISH STRATEGIES FURTHER DOWNSTREAM FOR MANAGEMENT OF ACUTE AND CHRONIC PAIN, THE PAIN ERN, INTEGRATED APPROACHES FOR HEMODIALYSIS PATIENTS, AND PRAGMATIC AND IMPLEMENTATION STUDIES FOR MANAGEMENT OF PAIN, SOMETHING CALLED PRISM, ALL OF THESE ARE ACRONYMS THAT YOU'LL GET USED TO IN THE COURSE OF THE PRESENTATIONS OVER THE COURSE OF TODAY. SO THOSE WERE THE ITEMS IN THAT SERIES OF SIX THEMES, AND, AGAIN, IF YOU DIDN'T GET YOUR MIND AROUND ALL OF THOSE DON'T FEEL BADLY, WE'RE ALL STRUGGLING FROM DAY TO DAY OURSELVES TO BE SURE WE REALLY KNOW WHAT WE'RE TALKING ABOUT WHEN WE PUT FORWARD SUCH A COMPLICATED MULTI-COMPONENT PROJECT. FORTUNATELY THERE ARE EXPERTS AT NIH WHO ARE DEEPLY ENGAGED IN EVERY ONE OF THOSE, AND HAVE BECOME SO OVER THE COURSE OF THE PAST YEAR. SO I'M PRETTY CONFIDENT WE'RE MOVING THIS FORWARD IN A FASHION THAT'S GOING TO PRODUCE RESULTS. IF YOU THOUGHT THAT WAS COMPLICATED, LET ME NOW SAY SOMETHING ABOUT THE GOVERNANCE OVERVIEW BECAUSE THIS IS MAYBE MORE ELABORATE THAN WHAT YOU ARE USED TO, IF YOU'VE BEEN PART OF OUR USUAL PROCESS. JUST REMIND YOU, THE USUAL PROCESS, STUDY SECTION, THEY REVIEW THE APPLICATIONS FOR THEIR SCIENTIFIC MERIT, SECOND LEVEL OF REVIEW IS ONCE OF THE INSTITUTE ADVISORY COUNCILS WHICH THEN DECIDES BASED ON PROGRAM PRIORITIES SHOULD THEY JUST GO BY THE PRIORITY SCORES OR SHOULD THEY DO ADJUSTING TO SORT OF HIGHLIGHT SOME AND MAYBE DOWNGRADE OTHERS WHERE THERE'S ALREADY A LOT GOING ON. THAT'S JUST A TWO-LEVEL REVIEW PROCESS. FOR THIS PROGRAM, IT'S MORE COMPLICATED. AND FOR REASONS THAT I THINK YOU'LL UNDERSTAND WHICH INCLUDE THE REASON YOU'RE ALL HERE BECAUSE I THINK WE DO NEED IN SUCH AN IMPORTANT PUBLIC HEALTH CIRCUMSTANCE, AND WHEN IT INVOLVES SO MANY DIFFERENT INSTITUTES TO HAVE A WAY OF LOOKING ACROSS THE LANDSCAPE OF THE HEAL INITIATIVE INITIATIVE TO ACHIEVE THE RIGHT BALANCE OF HOW WE'RE UTILIZING THIS SUBSTANTIAL AMOUNT OF MONEY TO GET THE MOST SIGNIFICANT IMPACT. SO, THAT MEANS THAT MANY OF WHAT GOES ON, PROJECTS THAT GO ON AT NIH, ARE KIND OF CONDUCTED BY A SINGLE INSTITUTE WITH THEIR COUNCIL AND STUDY SICKS. SECTION. THIS IS MULTI-INSTITUTE TRANS-NIH RESEARCH, WITH THE BOXES I WANT TO WALK YOU THROUGH TO HELP YOU UNDERSTAND YOUR ROLE IN THAT PURPLE BOX OVER THERE BECAUSE THAT'S YOU, THE HEAL MULTI-DISCIPLINARY WORKING GROUP. A SPECIALIZED WORKING GROUP OF NINDS, NIDA AND OTHER IC COUNCILS TO TRY TO PROVIDE INPUT. HOW DOES THIS PLAY OUT IN PRACTICE? I'LL BLOW THIS UP IN A MINUTE. LET ME EXPLAIN WHAT THE FOUR BOXES ARE HERE. THAT'S YOU. I'LL SAY MORE ABOUT THAT. AT THE TOP OF THIS IS "HEAL" EXECUTIVE COMMITTEE, WHICH INVOLVES SEVERAL NIH INSTITUTE DIRECTORS, MOST HERE AROUND THE TABLE OR WILL BE AT OTHER TIMES WHEN THE GROUP MEETS BECAUSE AFTER A COUNCIL MADE A RECOMMENDATION ABOUT WHAT TO FUND, USUALLY THEN THERE'S AN INSTITUTE DIRECTOR WHO SAYS, YES, CHECKS AND SIGNS OFF. AGAIN HERE IT'S NOT JUST ONE INSTITUTE IT'S A DOZEN OF THEM, WE NEED TO HAVE THAT ROLE PLAYED OUT IN A CORPORATE FASHION, THE COMMITTEE IS ABOUT RECEIVING INPUTS FROM ALL REVIEWS AND RECOMMENDATIONS AND THEN ULTIMATELY SAYING THIS IS WHAT WE'RE GOING TO DO. WE HAVE TO DO THAT AS OUR GOVERNMENT RESPONSIBILITY. THAT GROUP HAS ALREADY STARTED TO MEET ONCE A MONTH, I THINK WE'VE HAD A GOOD START. ALSO GETTING OURSELVES CLEAR ABOUT WHAT THE ROLES OF THE VARIOUS GROUPS WILL BE, AND THEIR PRESENCE HERE TODAY IS AN INDICATION ABOUT HOW MUCH THEY ARE VERY MUCH DEDICATED TO MAKING SURE THIS SOMEWHAT COMPLICATED PROCESS PLAYS OUT EFFECTIVELY. IN THE YELLOW BOX IS A REPRESENTATION OF MULTIPLE FEDERAL PARTNERS TO JUST LET YOU KNOW THAT WE RECOGNIZE WE'RE NOT IN THIS PARTICULAR ENTERPRISE ALL BY OURSELVES, IN HHS WE HAVE A CRITICAL ROLE WORKING WITH SAMHSA, ELLIE MCCANNTZ KATZ TO LING UP WITH THEIR RESPONSIBILITIES IN TERMS OF HOW THEY ARE SUPPORTING TREATMENT EFFORTS IN THE STATES, WE SPEND TIME WITH ELLIE AND HER TEAM. I MENTIONED BRETT GIREAX, ASSISTANT SECRETARY FOR HEALTH WHO DEVOTED PERSONAL TIME, SURGEON GENERAL, CDC, THE FDA IS GOING TO BE CRITICAL FOR A LOT OF WHAT WE'RE DOING, AND THEY HAVE AGREED TO PLAY A SIGNIFICANT ROLE IN ALL OF THE DISCUSSIONS WE'VE HAD SO FAR AND WILL E GOING FORWARD AS WELL. CMS HAS ALREADY COME UP THIS MORNING AS CRITICAL PART OF NOT ONLY WHAT DO WE FIGURE OUT WORKS BUT HOW DOES IT GET REIMBURSED, A JOINT LEADERSHIP FORUM IS TACKLING THOSE ISSUES, WE WANT TO BE SURE TO DO SO. OUTSIDE OF HHS THOUGH THERE'S OTHER PARTNERS. WE HAVE TO THINK CLOSELY ABOUT -- AND I WOULD PARTICULARLY HIGHLIGHT THE V.A., DEPARTMENT OF JUSTICE. AND AGAIN THE CRIMINAL JUSTICE SYSTEM AS AN OPPORTUNITY HERE FOR INTERACTIONS IS IMPORTANT. WE DON'T NEED YOU TO NECESSARILY HELP US BUILD THOSE LIAISE ANSWER. -- LIAISONS, IT'S IN PLACE, BUT IT MAY COME UP, IT DID THIS MORNING, HOW TO MAXIMIZE OUTCOMES. WE'RE PAYING CLOSE ATTENTION. THE BLUE BLOCKS IS MORE WHAT HAPPENS IN THE FACE OF WE HAVE NOW FUNDED THIS BIG COMPLICATED PORTFOLIO OF INTERSECTING RESEARCH PROGRAMS, HOW DO WE BE SURE IT WORKS? THAT MEANS WE NEED TO BRING TOGETHER SENIOR NIH SCIENTIFIC STAFF, PROGRAM STAFF GENERALLY, FROM 12 DIFFERENT INSTITUTES WHO WILL HAVE THE RESPONSIBILITY FOR TRACKING HOW THESE PROGRAMS ACTUALLY PLAY OUT, CHECKING TO SEE WHETHER THEY ARE RUNNING INTO OBSTACLES, LOOKING AT THEIR REPORTS OF PROGRESS AND SO ON. AND ALSO BRINGING THE PROGRAM STAFF TOGETHER SO THAT THEY ARE ALL CLEAR ABOUT WHAT WE'RE TRYING TO ACCOMPLISH. THAT MEANS THOSE TEAMS ARE GOING TO BE BROKEN DOWN INTO SORT OF SIX SUBGROUPS, THEY WILL FIT THE SIX CIRCLES YOU SAW AROUND THE BIG CIRCLE, AND THEY HAVE MET ONCE TO BEGIN TO FIGURE OUT HOW THEY ARE GOING TO FUNCTION EVEN THOUGH THEY ARE WAITING AT THE MOMENT FOR GRANT DECISION MAKING TO HAPPEN, SO THEY CAN TAKE ON THEIR APPROPRIATE APPROPRIATE ROLE, OVERSEEING AND MANAGING RESULTS. NOW WE'LL COME BACK TO THE PURPLE BOX, WHICH IS YOU, IN TERMS OF WHY DID WE PUT YOU TOGETHER AND WHY DID WE ASK YOU TO SPEND ALL THIS TIME WITH US AND WHAT IS IT WE'RE SEEKING TO GET FROM YOU? IN A NUTSHELL, IT'S TO HELP US ACHIEVE THE RIGHT BALANCE SO THAT WE ARE TAKING THE RESOURCES WE'VE BEEN GIVEN AND GETTING THE MAXIMUM BENEFIT FROM IT. WE WANT TO BE GOOD STEWARDS OF THESE RESOURCES, ON BEHALF OF THE PUBLIC. SO, LET ME BLOW UP A LITTLE BIT MORE ABOUT WHAT'S IN THAT PURPLE BOX. YOU PROBABLY ALREADY HEARD THIS. I'LL SAY IT ONE MORE TIME. YOU'RE NOT A COUNCIL. YOU'RE A WORKING GROUP. THAT HAS ADVANTAGES IN TERMS OF YOUR FUNCTIONS BECAUSE THOSE OF YOU WHO WERE NOT ALREADY SGEs DIDN'T HAVE TO BECOME SGEs IN ORDER TO SERVE ON THIS WORKING GROUP. IF YOU'VE NOT GONE THROUGH THAT PROCESS, YOU WILL BE GLAD YOU DIDN'T HAVE TO THIS TIME BECAUSE IT IS THAT DREADED DOCUMENT, 450, WHICH DOES REQUIRE -- I'M SORRY, LARRY. I'M DUMPING ALL OVER OUR ETHICS PROCESS. IT IS KIND OF A BIG DEAL. BUT IT ALSO MEANS THAT YOU HAVE A BIT MORE OF A NIMBLE ATTITUDE IN TERMS OF THINGS THAT YOU CAN DO SWIFTLY TO HELP US, BUT IT DOES MEAN THAT EVERY DELIBERATION THAT COMES OUT OF THIS MULTI-DISCIPLINARY WORKING GROUP HAS TO THEN BE PASSED ON TO A COUNCIL, OTHERWISE WE'RE NOT LIVING UP TO THE REQUIREMENTS IN STATUTE OF HOW DECISIONS ARE MADE. A LOT WILL GO TO NINDS AND NIDA COUNCIL, A LOT IS IN THEIR ZONE, BUT THERE WILL BE OTHER I.C. COUNCILS LIKE NCATS THAT WILL PROVIDE EXPERT INPUT IN VARIOUS TIMES SO YOU'LL HAVE THAT KIND OF REPORTING PROCESS AS WELL. SO, YOU CAN READ IN THE PRINT THERE UNDERNEATH SOMETHING ABOUT YOURSELVES. YOU ARE A SPECIALIZED WORKING GROUP. THERE'S 16 WORKING GROUP MEMBERS. SOME OF YOU ARE COUNCIL MEMBERS ALREADY. SOME ARE AD HOC. I SAID AT THE BEGINNING WE WILL NOT ASK YOU, YOU'LL BE GLAD, TO REVIEW EVERY ONE OF THE 40+ FOAs OR PROGRAMS. SOME WILL GO DIRECTLY TO THE RELEVANT I.C. COUNCIL BECAUSE IT'S VERY CLEAR THAT'S WHERE THEY FIT. THE ONES WE NEED YOUR HELP ON ARE THE ONES THAT ARE MORE TRANS-INSTITUTE, TRANSDISCIPLINARY, WHERE WE COULD DECIDE TO GO ONE WAY OR THE OTHER IN TERMS OF EXACT BALANCE OF FUNDING. THAT'S WHERE WE'RE GOING TO SEEK YOUR SPECIFIC GUIDANCE. YOU'LL PROVIDE US WITH INPUT THEN ON THE STATE OF THE SCIENCE, IN "HEAL" RESEARCH AND PAIN CONDITIONS, INCLUDING THE THINGS YOU SEE LISTED THERE. "HEAL" IS SUPPOSED TO BE BROKEN UP INTO A PAIN FOCUS SUBGROUP AND ADDICTION FOCUS SUBGROUP, WE'LL DO MORE IN FUTURE MEETINGS. THIS TIME WE'RE DOING A PLENARY ALL THE WAY THROUGH. BUT AS WE GET INTO SPECIFIC CONSIDERATIONS ABOUT THE RESULTS OF VARIOUS REVIEWS THAT YOU WILL BE ASKED TO LOOK AT, IN MAY, WE WILL HAVE MORE OF AN OPPORTUNITY TO DO THAT KIND OF DIFFERENTIATION. THERE'S MORE. SO, A VERY IMPORTANT PART OF THE HEAL INITIATIVE, ONE THAT WE'RE SPENDING A LOT OF TIME MAKING SURE WE'VE SET UP IN AN IDEAL FASHION IS THE OPPORTUNITY FOR PUBLIC/PRIVATE PARTNERSHIP. IF WE'RE SERIOUS ABOUT TRYING TO FIND REALLY NOVEL APPROACHES FOR CHRONIC PAIN AND FOR ADDICTION, THERE ARE A LOT OF RESOURCES, A LOT OF ASSETS, A LOT OF TALENT THAT DOES NOT EXIST CURRENTLY IN ACADEMIA BUT EXISTS IN THE PRIVATE SECTOR. WE PARTNERED WITH THE PRIVATE SECTOR IN OTHER CIRCUMSTANCES TO CONSIDERABLE BENEFIT. THE ACCELERATING MEDICINES PARTNERSHIP, AMP, WHICH I HAD THE PRIVILEGE OF SERVING A CO-LEAD WITH PFIZER, PARKINSON'S, LUPUS, NOW CONSIDERING ANOTHER PROJECT ON SCHIZOPHRENIA, THOSE HAVE BEEN I IN THE PRE-COMPETITIVE SPACE PROVIDING OPPORTUNITIES FOR INDUSTRY AND ACADEMIC SCIENTISTS TO SIT AROUND THE SAME TABLE AND WORK TOGETHER IN A FASHION THAT'S BEEN QUITE CATALYTIC, IN THOSE INSTANCES COSTS HAVE BEEN SHARED BETWEEN NIH AND INDUSTRY, AND SO THE IDEA OF DOING SOMETHING LIKE THIS FOR "HEAL" WAS VERY MUCH ON THE TABLE FROM THE VERY BEGINNING. THERE ARE, AS WE UNDERSTAND IT, AND YOU'LL LEARN MORE AS WE GO THROUGH, AS MANY AS 60 POTENTIALLY PROMISING PHARMACOLOGICAL INTERVENTIONS FOR CHRONIC PAIN THAT ARE SOMEWHERE IN THE SPACE BETWEEN PRE-CLINICAL ANALYSIS AND SOME OF THEM ALREADY IN PHASE 1 OR EVEN PHASE 2 TRIALS, BUT HAVE BEEN MOVING AT A RELATIVELY MODEST PACE, WITHOUT A LOT OF SHARING BETWEEN INDUSTRY IN TERMS OF WHAT THEY HAVE LEARNED WHICH MEANS IT'S POSSIBLE THAT SOME TARGETS ARE BEING APPROACHED THAT WERE ALREADY KNOWN NOT TO BE WORKING, AND OTHERS MAY BE APPROACHED NOT NEARLY WITH THE VIGOR THEY SHOULD BECAUSE IT LOOKS LIKE THEY MIGHT BE QUITE PROMISING. THE IDEA OF TRYING TO DO THIS KIND OF SHARED ENTERPRISE AND BRINGING TO BEAR UPON IT THINGS LIKE NIH AND ITS TRIAL NETWORKS YOU'LL HEAR ABOUT EPPIC-Net, SEEMED LIKE SOMETHING WE REALLY SHOULD FOCUS ON AND MAKE A PRIORITY OF "HEAL." THERE WAS A DEBATE ABOUT A YEAR AGO, OF CONSIDERABLE INTENSITY, ABOUT WHETHER IN FACT THERE WAS A SITUATION HERE THAT WE SHOULD BE THOUGHTFUL ABOUT IN TERMS OF RECEIVING NOT JUST ASSETS, NOT JUST COMPOUNDS, BUT ALSO MONEY FROM INDUSTRY TO CO-SUPPORT THIS EFFORT. THE FOUNDATION FOR NIH WHO HAS BEEN THE PROJECT MANAGER FOR THE PUBLIC/PRIVATE PARTNERSHIPS AND WE'LL BE HERE AS WELL CONVENED THEIR BOARD AND ULTIMATELY FELT THIS WAS NOT THE KIND OF THING THAT THE BOARD WOULD SUPPORT, THAT THEY WERE CONCERNED GIVEN THE FACT THAT INDUSTRY PLAYED SOUGHT ROLE IN THE OPIOID CRISIS, THAT NOW RECEIVING MONEY FROM INDUSTRY TO DEVELOP ALTERNATIVES MIGHT PRESENT A REPUTATIONAL RISK. NIH HAD ITS OWN WORKING GROUP THAT LOOKED AT THIS INTENSIVELY OVER THE COURSE OF A COUPLE MONTHS AND CAME TO THE SAME CONCLUSION. THAT WAS NOT REALLY QUITE THE CONCLUSION I ULTIMATELY EXPECTED BUT IT WAS CLEARLY PUT FORWARD AND WE DID DECIDE THE PARTNERSHIP IS CRUCIAL, WE HAVE OPPORTUNITIES BUT WE'LL FUND THIS BY NIH CONTRIBUTIONS, WHAT WE'RE ASKING FROM INDUSTRY IS IDENTIFICATION OF ASSETS, PROMISING COMPOUNDS, DEVICES, DATASETS, COULD BE CONTRIBUTED TO THIS KIND OF PARTNERSHIP EFFORT DONE IN AN OPEN ACCESS WAY, AND THAT NIH WOULD FUND THE EFFORT, FNIH WOULD PROVIDE PROJECT MANAGEMENT. THAT'S WHAT'S HAPPENED. THAT MEANS THAT WE HAVE A GROUP THAT HAS TO NOW LOOK AT THAT PORTFOLIO OF POSSIBLE ASSETS AND DECIDE HOW TO GO FORWARD. THAT'S WHAT THE "HEAL" PARTNERSIP COMMITTEE IS. IT IS A SUBGROUP OF YOU ALL. SOME OF YOU ARE ON IT. IN FACT THREE MEMBERS OF THIS GROUP ARE ALSO PART OF THE "HEAL" PARTNERSHIP COMMITTEE, WHICH WILL HAVE ITS FIRST MEETING TOMORROW. AND THE INITIAL EFFORTS THERE WILL BE TO DEVELOP A PROCESS WHICH MEANS TEMPLATE OF EVALUATING THE VARIOUS ASSETS BEING OFFERED UP BY INDUSTRY. IT'S A VERY IMPRESSIVE LIST, TRYING TO FIGURE OUT WHICH OF THOSE ARE MOST APPROPRIATE TO PUT THE HIGHEST PRIORITY INTO AND THE FINANCES INTO TO TEST HOW TO MOVE THEM FORWARD ULTIMATELY IN A WAY THAT MIGHT BENEFIT THE PUBLIC. SO THAT'S WHAT THE HEAL PARTNERSHIP COMMITTEE IS. THEY REPORT OFFICIALLY THROUGH YOU, YOU IN TURN REPORT THROUGH THOSE COUNCILS. THE COUNCILS IN TURN REPORT TO THE EXECUTIVE COMMITTEE. YOU'RE GETTING WORRIED ABOUT ALL THE LAYERS. WE HAVE WORRIED ABOUT THAT A LOT, ESPECIALLY BECAUSE, REMEMBER, THAT 8 $50 MILLION HAS TO SPENT BY OCTOBER 1. WE DON'T HAVE CARRYOVER AUTHORITY THIS YEAR. IT'S GOING TO BE CRAZY. THIS MEETING TODAY SEEMS FAIRLY RELAXED. WE'RE NOT ASKING YOU TO MAKE BIG DECISIONS, BUT IT'S GOING TO START TO ESCALATE HERE, WHEN WE MEET IN MAY AND AUGUST IT WILL BE AT A HIGHER FEVER PITCH IN TERMS OF MAKING THE RIGHT DECISION. BUT I'M CONFIDENT WE CAN MAKE THAT ALL WORK. I SHOULD HAVE SAID AT THE BEGINNING, DR. REBECCA BAKER, WHO YOU HEARD FROM IN THE INITIAL WELCOME, AS DIRECTOR IN THE OFFICE OF DIRECTOR IS A PERSON OF CONSIDERABLE TALENT AND DETERMINATION TO DRIVE THIS PROCESS, SO WATCH OUT IF SHE GIVES YOU A RECOMMENDATION, IT'S PROBABLY SOMETHING YOU'LL NEED TO DO. >> DR. COLLINS -- >> ONE MORE THING. THE HEAL PARTNERSHIP FORUM, THE PURPLE BOX, IS ANOTHER OPPORTUNITY WITH INDUSTRY TO HAVE AN OPEN DISCUSSION WHICH WE WILL DO ROUGHLY EVERY SIX MONTHS ABOUT HOW THIS IS ALL GOING.& THE HEAL PARTNERSHIP COMMITTEE IS GOING TO BE REALLY DRILLING DOWN INTO THE NITTY-GRITTY OF HOW DO YOU PRIORITIZE VARIOUS ASSETS. THIS TARGET OR THAT TARGET. THE PARTNERSHIP FORUM IS AN OPPORTUNITY TO DISCUSS WHETHER WE'VE GOT THIS MODEL RIGHT IN TERMS OF INTERACTIONS BETWEEN INDUSTRY AND ACADEMIA AND NIH. YES, WALLY? >> ONE CONCERN THAT I HAVE, MAYBE YOU'VE ALREADY ADDRESSED IT, IF YOU HAVE A PROPRIETARY ASSET, WHY WOULD YOU SHARE IT WITH THE REST OF THE WORLD? AND ANOTHER WAY OF SAYING THAT IS ONLY YOUR CASTOFFS WOULD GET SHARED AND YOU WOULD KEEP THE BEST FOR YOURSELF. YOU PROBABLY THOUGHT THIS THROUGH BUT I'M INTERESTED IN HOW -- AND THIS IS SPEAKING FROM PERSONAL EXPERIENCE. WE GOT UG3/UH3 FUNDED, AND AN ASSET THAT WAS SAID TO HAVE BEEN AVAILABLE WAS THEN WITHDRAWN, AFTER FUNDING. >> YEAH, THAT MUST HAVE BEEN FRUSTRATING. VERY PERCEPTIVE QUESTION. WHEN YOU LOOK AT THE LIST OF 60 ASSETS THAT HAVE BEEN TENTATIVELY PUT FORWARD, I SUSPECT THERE ARE SOME DOGS IN THERE THAT MAYBE AREN'T WORTH PURSUING BUT FOR THE MOST PART THESE ARE COMPOUNDS THAT HAVE BEEN MOVING VERY SLOWLY OR GOT DROPPED BECAUSE THE MARKET DIDN'T LOOK LIKE IT WAS APPEALING OR THERE WAS SOME OTHER HANGUP ALONG THE WAY SO I THINK MOST OF THESE ARE HIGHLY WORTHWHILE, CONSIDERING. BUT NOW TAKE THAT AS IT IS, WE WILL HAVE THIS PROCESS. THAT'S WHAT THE HEAL PARTNERSHIP COMMITTEE IS GOING TO START DOING TOMORROW, SIFT THROUGH, IF THERE ARE THINGS OFFERED UP THAT ARE CLEARLY CLUNKERS THEY ARE NOT GOING ANYWHERE. SOMEWHERE IN THE GROUP I SUSPECT THERE ARE SOME PRETTY EXCITING OPPORTUNITIES THAT WOULD OTHERWISE SIT ON THE SHELF AND CAN NOW BE ACCELERATED. WALTER MAY WANT TO SAY SOMETHING HERE. >> YEAH, SO, I WOULD GO WITH FRANCIS' ANSWER IN TERMS OF WHAT THE BIG COMPANIES WOULD BE DOING, AND THERE ARE SOL -- SOME BIG COMPANY AROUND THE TABLE WHO CAN MAYBE PITCH IN THAT WE'LL HAVE THE ABILITY TO TEST THINGS IN COHORTS THAT THEY MAY NOT ACTUALLY HAVE ON THEIR RADAR SCREEN OR FOR VARIETY OF DIFFERENT REASONS SO A DRUG THAT'S BEING, YOU KNOW, PIONEERED FOR ONE TYPE OF PAIN BY THE INDUSTRY WE MIGHT BE ABLE TO FIND IT'S REALLY VALUABLE IN AN AREA OF HIGH UNMET NEED. I THINK THE OTHER THING FROM OUR EXPERIENCE DOING TRANSLATION AT NIH A LOT OF SMALL BIOTECH COMPANY WHO IS DON'T HAVE THE RESOURCES TO DO A PHASE 2 TRIAL WE WILL MAKE THOSE RESOURCES AVAILABLE. IF SUCCESSFUL, THEN THEY CAN ACTUALLY RAISE CAPITAL OR THEY CAN MAKE DEALS WITH BIGGER COMPANIES. SO I THINK THERE WILL BE A LOT OF ACTIVITY IN THAT SPACE, AND WE CAN TALK ABOUT THE DEVICE WORLD AS WELL, WHICH IS HEAVILY SMALL BIOTECHS WORKING ON THINGS AS WELL. >> GOOD POINT. JESSICA? >> A QUESTION ABOUT THE 60 ASSETS IDENTIFIED, ARE THEY ALL IN THE PAIN SPACE, ARE THERE ANY FOR TREATMENT OF SUBSTANCE USE DISORDER OR OPIOID USE DISORDER? >> MOSTLY IN THE MAIN SPACE BUT SOME ARE PERHAPS BIFUNCTIONAL. THAT'S AN IMPORTANT ISSUE WE NEED TO KEEP LOOKING AT. SO THAT WAS MY HOPEFULLY NOT TOO SCARY REPRESENTATION HOW YOU FIT INTO THIS SCHEME. AGAIN, YOU THERE AS MULTI-DISCIPLINARY WORKING GROUP ARE IN A CRITICAL PLACE TO HELP US AS WE GO THROUGH THESE MONTHS OF DECISION MAKING. LET ME TURN IT OVER TO NORA. NO ONE WILL BE SURPRISED THAT WE WERE AHEAD OF TIME UNTIL THE DIRECTOR STARTED SPEAKING AND NOW WE'RE BEHIND. >> FRANCIS, GOOD MORNING. AGAIN, THANKS TO ALL OF YOU FOR YOUR WILLINGNESS TO SERVE IN THIS MULTI-DISCIPLINARY WORKING GROUP. I DO ALSO WANT TO THANK MY COLLEAGUES AT THE NIH AND CERTAINLY IN PARTICULAR FRANCIS BECAUSE I'VE BEEN DIRECTOR OF NIDA FOR 16 YEARS, COMING INTO 16 YEARS, SO THAT INSTITUTE ULTIMATELY HAS BEEN WORKING ON HOW DO YOU PREVENT AND TREAT SUBSTANCE USE DISORDERS, ADDICTION INCLUDING OPIOIDS BUT HAS NEVER BEEN UNTIL FRANCIS BECAME DIRECTOR THAT THE NIH ITSELF HAS BEEN CENTERED ON TRYING TO ADDRESS THE CRISIS AND I'M THANKFUL, NOT JUST BECAUSE OF HIS LEADERSHIP AND ENERGY BUT BECAUSE HE HAS BROUGHT US ALL TOGETHER. HE HAS EVERYBODY THINKING IN INSTITUTES IN THE PAST NEVER THOUGHT THEIR KNOWLEDGE COULD BE VALUABLE TO THE PROBLEM OF ADDICTION AND PAIN. WE'RE ALL THINKING TRYING TO MAXIMIZE HOW EXPERTISE TO ADDRESS THE CRISIS BECAUSE INDEED THE CRISIS ACTUALLY FORCING US TO RECOGNIZE TIME IS NOT ON YOUR SIDE. WE'RE DEALING WITH AN URGENT CRY IS. I THANK DR. LARRY TABAK AND REBECCA, IT'S AMAZING TO HAVE THE DIVERSE GROUP OF PEOPLE, AND MY TEAM AT NIDA, JACK STEIN, AND MEMBERS FROM THE CLINICAL TRIALS NETWORK, BETTY TAI, YOU'LL BE HEARING FROM HER. THE REALITIES, WE'VE BEEN DEVELOPING MEDICATIONS, NEW CLINICAL TRIAL PROJECTS, WE'VE BEEN WORKING WITH CRIMINAL JUSTICE SYSTEM FOR MANY, MANY YEARS. WHAT THE HEAL INITIATIVE ALLOWS US TO DO, BRINGS UP MANY MORE RESOURCES ON THE ONE HAND, BUT IMPORTANTLY IT ALSO CREATES ACCELERATES OUR ABILITY TO DO PARTNERSHIPS. AND IN PONDERING IN THE REMARKABLE PRESENTATIONS THAT WE HEARD THIS MORNING, THAT REPRESENT THE VOICES OF ADDICTION AND PAIN. IT HIT ON ME THAT WERE THREE SUBJECT THINGS, THE NOTION OF STIGMA. STIGMA IS SOMETHING THAT OF COURSE WE'VE BEEN STRUGGLING ALL ALONG, AS A PHYSICIAN MY PERSPECTIVE HAS BEEN IF WE CAN CHANGE STIGMA THEN PEOPLE WILL BE MUCH MORE WILLING TO NOT JUST ACCEPT ADDICTION AS A DISEASE BUT IMPORTANTLY A DISEASE THAT NEEDS TO BE TREATED IN THE HEALTHCARE SYSTEM. WITH THE CRISIS WHAT WE'VE BEEN SEEING, AN OPENING ON THE ONE HAND OF WILLINGNESS OF HEALTHCARE SYSTEM TO RECOGNIZE THAT THEY CAN AND SHOULD PARTICIPATE IN ITS TREATMENT, ON THE ONE HAND. AND AT THE SAME TIME, FOR THE LAY PUBLIC TO RECOGNIZE THAT THERE'S NOTHING TO BE INTIMIDATED ABOUT ADDICTION, AND SO YOU ALWAYS SEE THESE AS AN OPPORTUNITY. AND THEN WEEK AGO MONDAY I WAS VISITING ONE NEW FACILITY FOR THE TREATMENT OF ADDICTION, INPATIENT FACILITY, REALLY PRETTY SPECTACULARLY WELL BUILT, AND I'M SPEAKING WITH THE DIRECTOR WHO HAS BUILT SEVEN OF THESE FACILITIES IN PENNSYLVANIA, NEW YORK, AND MARYLAND. SHE SAID, NORA, EVERY SINGLE TIME I BRING ONE OF THESE FACILITIES, I'VE BEEN THREATENED BY MULTIPLE PEOPLE, THREATENED BY MY LIFE. AS RECENTLY AS A FEW MONTHS AGO. THIS BROUGHT IT TO MY NOTION, THAT'S WHERE THE STIGMA IS. PEOPLE DON'T WANT TREATMENT IN THEIR NEIGHBORHOODS. THAT'S A REFLECTION OF WHAT WE'RE AFTER. ONE OF MY PERSPECTIVES, WE'RE IN A POSITION TO CHANGE IT. I THINK THE HEAL INITIATIVE HAS THE CAPACITY, ONE, TO MODIFY THAT STIGMA BECAUSE KNOWLEDGE, AS WAS MENTIONED BEFORE IN HIV, WAS ULTIMATELY WHAT LED TO A DESTIGMATIZATION OF THE DISEASE RAPIDLY. WE CAN DO IT. I'LL SHOW YOU SOME INITIATIVES FRANCIS ALLUDED TO THAT GIVE US THAT OPPORTUNITY. THE OTHER IS PARTNERSHIPS. WE'RE NOT GOING TO ADDRESS IT UNLESS WE BUILD UP NOT JUST PARTNERSHIPS AMONG AGENCIES AND BETWEEN AGENCIES, PUBLIC/PRIVATE PARTNERSHIPS, AND PARTNERSHIPS WITH PATIENT GROUPS. HEAL INITIATIVE OFFERS OPPORTUNITY OF DEVELOPING NEW PROCEDURES. WE DO SCIENCE. IT IS A VALID QUESTION WHAT ARE THE STRATEGIES OR MECHANISMS THAT WE CAN DO TO ACCELERATE THOSE PARTNERSHIPS. AND FINALLY THE THIRD POINT, HOW LONG IT TAKES TO TRANSLATE SCIENCE INTO PRODUCTS THAT CAN HELP PREVENT AND TREATMENT, I AGREE, 14 YEARS IS UNACCEPTABLE. I THINK THAT WHAT WE NEED TO DO IS HOW DO WE MODIFY? GUYS, WE'RE IN THE POSITION TO MODIFY. THESE THINGS ARE DONE BY ALL OF US IN DIFFERENT LEVELS. MY CHALLENGE IS LET'S TAKE THESE AS AN OPPORTUNITY TO SAY WE CAN DO BETTER. IN FACT WE HAVE A TRACK RECORD ALREADY OF BRINGING A PRODUCT FROM ITS INCEPTION INTO THE CLINIC IN THREE YEARS. THE NASAL NARCAN. BY WORKING WITH INDUSTRY, WITH RESEARCHERS SO YES, WE HAVE DONE THINGS IN THE PAST A CERTAIN WAY, BUT IT STRIKES ME THAT RIGHT NOW THE CRISIS IS TELLING. WE CANNOT CONTINUE TO DO THINGS THE WAY WE DID THEM IN THE PAST. I THINK THE HEAL INITIATIVE PUSHES US IN THERE. WHERE ARE WE WITH THE CRISIS? AGAIN, MY VIEW IS WE GATHER DATA, THAT'S WHAT SHOULD LEAD US TO UNDERSTAND BETTER AND PLAN BETTER. THIS IS THE CRISIS, THE OPIATE CRISIS IS CHANGING RAPIDLY. WHAT WORKED IN 2005 IS NO LONGER SUFFICIENT. CRISIS, NUMBER OF FATALITIES FROM OVERDOSES, I'M NOT IN ANY WAY EVEN TOUCHING THE OTHER NARRATIVE CONSEQUENCES, WHICH ARE MULTIPLE, PRESCRIPTION OPIOIDS, WAS THE MAIN DRIVER UNTIL 2011. IF WE MODIFIED THE WAY WE WERE PRESCRIBING OPIOIDS AND MAKING THEM AVAILABLE WE COULD HAVE SOLVED THE CRISIS. WE WOULD HAVE REDUCED DRAMATICALLY THE DEATHS. THAT'S NO LONGER SUFFICIENT. IN FACT MODELERS HAVE ACTUALLY DETERMINED THAT RIGHT NOW WE WILL DECREASE THE MORTALITY BY VERY LITTLE, NOW IT'S BEING TAKEN OVER BY VERY PURE HEROIN AT LOW COST, VERY HIGH QUANTITIES, ALSO THE THIRD LINE, BLACK LINE, IN TERMS OF MORTALITY DRIVING INCREASES OVER THE PAST FOUR YEARS, SYNTHETIC OPIOIDS, WITH ALL SYNTHETIC DRUGS, CANNABINOIDS AND STIMULANTS, THEY ARE TO STAY. THIS IS THE LINE OF THE FUTURE. THEY ARE MORE POTENT THAN OTHER DRUGS OF ABUSE, EASIER TO BRING IN, MUCH HARDER TO REGULATE. NOW WE NEED TO ADDRESS IMPORTANCE OF PROVIDING PATIENTS WITH PAIN, WITH PROPER TREATMENT, BECAUSE OTHERWISE IT WOULD JUST SORT OF STIGMATIZE EVERYTHING. THEY WILL GO TO THE BLACK MARKET TO GET OPIOIDS. WE NEED TO ADDRESS THEIR NEEDS. WE NEED TO ADDRESS THE ISSUE OF HOW DO WE CONTROL HEROIN ADDICTION, SO WE'RE SEEING SIGNIFICANT INCREASES IN THE NUMBER OF INDIVIDUALS THAT NOW ARE BECOMING ADDICTED TO OPIOIDS, NOT AS WE WERE SEEING IT FIVE YEARS AGO FROM TRANSITION OF PRESCRIPTION TO HEROIN BUT INITIATING ADDICTION TO OPIOIDS WITH HEROIN AND THEREFORE THE SAME THING WITH FENTANYL. AS WE DEAL WITH PREVENTION, BETTER PRESCRIPTION PRACTICES ARE FUNDAMENTAL, BUT WE NEED TO ALSO ADDRESS THE NOTION OF HOW DO WE PREVENT SUBSTANCE USE IN INDIVIDUALS SO THEY DON'T END UP TAKING HEROIN OR FENTANYL. THAT IS THE CHALLENGE THAT WE HAVE. IT'S MUCH MORE COMPLEX. AS WAS MENTIONED ALREADY, WHAT WE'RE SEEING, IF YOU GO INTO THE COMMUNITIES, EFFECTIVE, PARTICULARLY APPALACHIAN AREAS, NORTHERN, EASTERN PARTS OF THE CORRIDOR OF THE UNITED STATES. THEY SAY, WHAT WE'RE SEEING IS MORE AND MORE DRUG COMBINATIONS, AND THE THING THAT'S CHALLENGING IS TYPE OF DRUGS PEOPLE ARE COMBINING ARE ACTUALLY CONSTANTLY CHANGING. FROM THE THERAPEUTIC PERSPECTIVE OF COURSE THAT IS A BIG CHALLENGE BUT WE NEED TO BE AWARE THAT IT'S THERE AS WE BUILD UP INTERVENTIONS. SO, WHERE ARE WE? WHERE YOU ARE RIGHT NOW IT'S LIKE I HAD THE MOMENT, OVER TWO YEARS FRANCIS AND LARRY AND I AND WALTER HAVE BEEN THINKING IN THE SAME ORDER WITH MANY, MANY MEETINGS, WHICH HAVE BEEN TO TRY TO ADDRESS WHAT ARE THE MOST URGENT NEEDS AS IT RELATES TO THE TREATMENT AND PREVENTION OF OPIOID DISUSE ORDER AND ADDRESSING NEEDS OF PATIENTS FROM PAIN. SO, THAT LEAVES AN ENORMOUS AMOUNT OF INFORMATION THAT WE'RE NOW COMPRESSING TO TRY TO IDENTIFY WHAT ARE SOME OF THE MAIN INITIATIVES THAT WE'RE GOING TO BE LAUNCHING WITH THE DOLLARS THAT CONGRESS GAVE US. SO, FOR THOSE OF YOU THAT ARE NOT ON THE OPIOID WORLD, WE'RE VERY, VERY LUCKY TO HAVE MEDICATIONS FOR THE TREATMENT OF OPIOID ADDICTION. WE DON'T HAVE THEM FOR METHAMPHETAMINES, WHICH BY THE WAY IS INCREASING. WE DON'T HAVE THEM FOR COCAINE. BY THE WAY, NUMBER OF DEATHS FROM COCAINE ARE ALSO SKYROCKETING. WE DON'T HAVE THEM FOR MARIJUANA. EVERYBODY IS LEGALIZING, BUT WE HAVE THEM FOR OPIOIDS. AND THEY ARE QUITE EFFECTIVE. YOU COMPARE MEDICATIONS WE HAVE FOR OPIATE ADDICTION AGAINST THE OTHER ONES, COME TO REALIZE THERE ARE AS GOOD AS ANTI-HYPERTENSIVES, ANTI-DIABETICS, SOMETIMES BETTER, BUT NOT BEING USED. NOT JUST IS THERE STIGMA FOR ADDICTION OR MEDICATIONS WE USE TO TREAT ADDITION, WE HAVE METHADONE, BUPRENORPHINE, NALOXONE. THESE THREE CLASSES OF MEDICATIONS HAVE BEEN DEVELOPED, REALLY VERY MUCH IN VERY, VERY PRODUCTIVE PARTNERSHIPS THAT HAVE GONE BETWEEN THE GOVERNMENT RESEARCH, MOST DONE AT NIDA, ALSO AGAIN WITH WILLINGNESS OF SOME COMPANIES THAT DESPITE STIGMA THERE IS AGAINST THE TREATMENT OF ADDICTION HAVE BEEN WILLING TO TAKE THE DRUG AND DEVELOP THEM. SO EVERY SINGLE STUDY THOSE THESE MEDICATIONS IMPROVE NEGATIVE OUTCOMES. EVERY ONE OF THEM. AND THEY IMPROVE SOCIAL FUNCTIONING, RETENTION AND TREATMENT. THEY DECREASE MORTALITY. HOW GOOD ARE THEY AT DECREASING MORTALITY? IF YOU'RE ON MEDICATION, YOU'RE TWO OR THREE TIMES LESS LIKELY TO DIE THAN NOT. AS CATEGORICAL AS THAT. WHY DON'T WE USE THEM? STIGMA. AS MENTIONED THROUGH THE HEAL INITIATIVE WE MATE BE ABLE TO ADDRESS IT. YOU MAY HAVE SUGGESTIONS. THAT'S GOING TO BE IMPORTANT. BUT THE OTHER COMPONENT TO IT IS WE DON'T HAVE SUFFICIENT INFRASTRUCTURE TO TREAT PATIENTS WITH THESE MEDICATIONS. THAT HAS WILL BE STUDIED BY MULTIPLE INVESTIGATORS. PART OF THE REASON WHY WE ARE IN SUCH A GAP IS THAT THE HEALTHCARE SYSTEM HAS NOT REALLY BEEN INVOLVED IN THE USE OF THESE MEDICATIONS FOR TREATMENT OR SCREENING ADDICTION, THANKED IS NOW FORCING THEM TO CHANGE BECAUSE THEY CAN NOT AFFORD NOT TO DO IT. AS A HEAL INITIATIVE, WE'RE SEEING AS A PRIORITY HOW DO WE DEVELOP IMPLEMENT STRATEGIES THAT ARE GOING TO WARNING? AND THEN I'M GOING THROUGH THE LAST ONE, MEDICATIONS ARE WONDERFUL, HOW EFFECTIVE THEY ARE BUT 50% OF PATIENTS WILL RELAPSE WIN SIX MONTHS AND THEIR RISK OF OVERDOSE DEATH IS VERY HIGH. HOW DO WE IMPROVE RETENTION? IF YOU LOOK AT BIG CHALLENGES, HOW DO WE EXPAND ACCESS TO TREATMENT FOR PATIENTS, THE SECOND ONE HOW DO WE ENSURE THAT THEY ARE IN TREATMENT, HOW DO WE DO THAT? THAT BRINGS US TO THE COMPONENT OF BASIC SCIENCE, PHARMACOLOGICAL STUDIES, DEVELOPMENTAL MEDICATIONS, IMPLEMENTATION AND SERVICES RESEARCH, AND THAT'S WHERE WE ARE HEADING. THAT'S HOW WE ACTUALLY MADE THE DECISIONS IN TERMS OF INITIATIVES. YOU SAW THESE FROM FRANCIS' PRESENTATIONS. IN THE OPIOID USE DISORDERS THERE ARE FOUR BUCKETS, EXPAND THERAPEUTIC OPTIONS WHICH RELATES TO THE CONCEPT OF NEW FORMULATIONS, ALTERNATIVE TARGETS FOR MEDICATIONS, APART FROM THE ONES WE HAVE. ALTERNATIVE DEVICE INTERVENTIONS THAT WE HAVE NOT REALLY PROPERLY EXPLOITED. ALTERNATIVE MEDICATIONS TO REVERSE OVERDOSES, ALTERNATIVE DEVICES, ACTUALLY ARE WAYS TO DEAL WITH BEHAVIORAL INTERVENTIONS THAT OTHERWISE COULD HELP US IMPROVE THE OUTCOMES IN PATIENTS. OPTIMIZE EFFECTIVE TREATMENT STRATEGIE. I MEAN, WE HAVE A LOT OF EVIDENCE THAT THINGS ARE WORKING BUT NOT BEING IMPLEMENTED BECAUSE IN MANY INSTANCES THE SYSTEMS THAT COULD IMPLEMENT THEM DON'T HAVE THE KNOW-HOW. THE THIRD BUCKET, DEVELOP NEW/IMPROVED PREVENTION AND TREATMENT STRATEGIES, WE'RE FACED IN THE PREVENTION WORD THAT OPIOID USE DISORDER, PREVALENCE IS LOW AMONG ADOLESCENCE AND SKYROCKETS IN THE TRANSITION TO ADULTHOOD AND HAVE NOT HAD EXPERIENCE WITH PREVENTIONS IN THAT AGE GROUP, SO THAT'S ONE OF THE STRATEGIES WE NEED TO EXPAND. THE FINAL ONE, ENHANCE TREATMENTS FOR INFANTS WITH NEONATAL ABSTINENCE SYNDROME, I WOULD BASICALLY REPHRASE THAT AND SAY IMPROVE OUTCOMES FOR INFANTS EXPOSED TO OPIOIDS, BUT ALSO IMPROVE OUTCOMES OF THOSE INFANTS POSTNATALLY IF THEY LIVE WHERE ONE OR BOTH PARENTS HAVE OPIOID USE DISORDER. THE NEGATIVE CONSEQUENCE MAY BE AS BAD OR EVEN WORSE POSTNATALLY THAN JUST EXPOSURE TO THE DRUGS. AND I THINK WE HAVE TO ADDRESS THAT. EXPAND THERAPEUTIC OPTIONS, OPIOID USE DISORDER, OVERDOSE REVERSAL, SOMETHING WE'VE BEEN DOING FOR MANY YEARS. WHAT NIDA HAS DONE IS ACTUALLY INCENTIVIZE PHARMACEUTICAL COMPANIES IN ORDER TO ACTUALLY BUY THE RISKING PRODUCTS TO GO IN AND TAKE FUNDING FROM RESEARCH AND BRING THEM INTO THE CLINIC. WE'RE PRIORITIZING PRODUCTS THAT COME IN RAPIDLY, WE NEED SOLUTIONS RAPIDLY. IN THAT SPACE THE HIGHEST PRIORITY IS NEW FORMULATIONS. AND AS CHRISTIN MENTIONED BEFORE, THERE'S A ONE-MONTH FORMULATION OF BUPRENORPHINE LIKELY TO MAKE IT MUCH EASIER FOR PATIENTS TO BE COMPLIANT WITH THEIR MEDICATIONS, AND REALLY SURE THEY ARE COVERED FOR AT LEAST A MONTH AS OPPOSED TO HAVING TO MAKE THE DECISION TO TAKE THE DRUG ON A DAILY BASIS. THIS WILL MAKE IT MUCH EASIER, EASY EASIER TO TREAT PATIENTS IN RURAL FACILITIES. WOULDN'T IT BE WONDERFUL IF WE COULD DEVELOP FORMULATIONS THAT CAN COVER FOR THREE MONTHS OR SIX MONTHS EVEN, AND I THINK THIS IS WHERE IT BEHOOVES US TO BE CREATIVE AND TECHNOLOGICAL ADVANCES. THE SAME ISSUE WITH OVERDOSE REVERSALS. THE NASAL SPRAY IS THE MAIN WAY NALOXONE IS BEING DELIVERED BUT WE'RE FINDING THAT CLINICIANS AND FIRST RESPONDERS ARE STATING THEY CAN NOT REVERSE PATIENTS THAT HAVE OVERDOSED. THEY CAN NOT REVERSE THEM, EVIDENTLY MANY ARE ON FENTANYL, MANY ARE ON DRUG COMBINATIONS, SO THE NEED TO ACTUALLY DELIVER HIGHER DOSES OF NALOXONE FROM THE ONES CURRENTLY AVAILABLE IN THAT NASAL SPRAY, TO DELIVER AN ANTAGONIST WITH A LONGER LIFE, OR TO DELIVER COMBINATION OR DRUGS THAT INTERACT OTHER THAN BEING ANTAGONISTS IN ORDER TO BE MORE SUCCESSFUL, TWO MAJOR, MAJOR PRIORITIES IN TERMS OF USING THE MEDICATION DEVELOPMENT FUNDS, WHICH BASICALLY THROUGH THE HEAL INITIATIVE HAS ALLOWED US TO DOUBLE RESOURCES WE HAVE TO DO IT AND ACCELERATE IT. WE'RE ALSO ENCOURAGING RESEARCHERS TO PARTNER WITH INDUSTRY TO DEVELOP ALTERNATIVE TARGETS FOR THE OPIOID USE DISORDER, AS WELL AS NEW INTERVENTIONS LIKE VACCINES AND IMMUNOTHERAPY, WE'RE ALSO REACHING OUT TO DEVICE COMPANIES TO HELP US DEVELOP SOLUTIONS. FOR EXAMPLE, ONE OF THE CHALLENGES WHEN PEOPLE OVERDOSE IS THAT THERE'S NOBODY AROUND. THEY MAY BE SLEEPING, NOBODY SEES THEM, NOBODY CAN ADMINISTER NALOXONE. SO WOULDN'T IT BE DESIRABLE TO HAVE A BIOSENSOR THAT COULD DELIVER NALOXONE WHEN SOMEONE IS GOING INTO AN OVERDOSE OR THAT CALLS IN A SAFETY SYSTEM TO DO AN INTERVENTION. THIS IS WHERE WE ARE BRINGING TOGETHER VERY DIFFERENT PERSPECTIVES AND HOW TO ADDRESS THIS PROBLEM IN MEDICATION DEVELOPMENT DEVICES TO IMPROVE OUTCOMES FOR PEOPLE SO THEY CAN STAY IN TREATMENT LONGER AND THEY ALSO CAN REVERSE OVERDOSES. AS AN AGENCY FORCED US TO RECOGNIZE WE NEED TO COME UP WITH MECHANISMS TO ACCELERATE THE PROCESS BY WHICH WE DO OUR REVIEW AND CAN DELIVER THE FUNDING. SO, WE HAVE ACTUALLY VERY -- WE'RE PROUD BECAUSE WE'VE DECREASED THAT TIME LINE IN ONE INSTANCE FOR THREE MONTHS. SO WE'RE ACCELERATING, PUTTING EVERYBODY THAT IS IN THE REVIEW PROCESS TO WORK IN ORDER TO BE ABLE TO MAKE THESE AND DEPLOY THESE RESOURCES FASTER. THEN DEVELOP IMPLEMENTATION STRATEGIES, BRING THE HEALTHCARE SYSTEM TO START TO SCREEN AND TREAT PATIENTS WITH SUBSTANCE USE DISORDER, AND WE'RE TAKING ADVANTAGE OF OUR CLINICAL TRIAL NETWORK LED BY LED BY BETSY TAI, PENETRATING THE HEALTHCARE SYSTEM TOE DEVELOP MODELINGS OF CARE FROM EMERGENCY DEPARTMENTS TO INFECTIOUS DISEASE DOCTORS TO PRIMARY CARE PHYSICIANS TO GENERATE MODELS WHERE YOU CAN TREAT THE PATIENTS AND SUPPORT THEM. ENGAGING IN THE PROCESS NURSES. THE MONEY THAT WE'RE GETTING WHICH IS DOUBLING FOR THE CLINICAL TRIAL NETWORK WILL BE DONE TO EXPAND AND CREATE MORE BRIDGES WITH OTHER HEALTHCARE SYSTEMS, AS WELL AS TO START TO GET INTO RURAL AREAS TO EXPAND ACCESS TO OPIOID USE DISORDERS, TO DEVELOP MODELS FOR LINKAGE TO CARE AND WE'RE ALSO EXPANDING OUR ABILITY TO GENERATE OPIATE REGISTRIES. THERE ARE A COUPLE SYSTEMS THAT HAVE BEEN SUCCESSFUL BUT IT HAS NOT ALWAYS BEEN EASY BECAUSE OF ISSUES OF PRIVACY AND WE DON'T KNOW WHAT ARE THE LONG-TERM OUTCOMES OF THE MANY PATIENTS WITH ADDICTION. AS YOU WILL HEAR FROM BETSY TAI LATER THIS AFTERNOON. ANOTHER AREA THAT WE HAVE BEEN WORKING FOR MANY YEARS IS THE JUSTICE SETTING, WE HAVE HAD TWO JUSTICE NETWORKS, ADULTS AND ADOLESCENTS, AND THESE ENABLE THOSE TO START TO CREATE A CADRE OF RESEARCHERS FROM ACADEMIA THAT WORK WITH JUSTICE DEPARTMENTS TO BRING IN EVIDENCE TREATMENTS INTO THE CRIMINAL JUSTICE SYSTEM. DESPITE THIS LESS THAN 3% OF PRISONS AND JAILS IN THE UNITED MEDICATIONS FOR OPIATE USE DISORDERS. WE WANT TO USE THE HEAL INITIATIVE AS AN OPPORTUNITY TO TRY TO CHANGE THIS. SO WE'RE NOW EXPANDING OUR ADULT NETWORK WITH JUSTICE, WORKING WITH THE JUSTICE DEPARTMENT, TO ACTUALLY USE IT NOT ONLY TO BRING INTO THOSE SITES BUT IMPORTANTLY TO CHANGE THE CULTURE THAT HAS TYPICALLY REJECTED THE USE OF MEDICATIONS OF THESE PATIENTS. AND THESE PATIENTS, PRISONERS, PEOPLE IN JUSTICE SETTINGS. A CRUCIAL ELEMENT, RESONATING WITH PARTNERSHIP, FOR US TO SUCCEED IS NOT JUST TO DELIVER THE TREATMENTS IN THE PRISONS AND JAILS BUT TO GENERATE THE BRIDGES INTO THE HEALTH CARE WHEN THE PRISONERS LEAVE PRISON, OTHERWISE 30 TO 40 TIMES HIGHER ONCE THEY LEAVE PRISON BECAUSE OF RISK OF OVERDOSE. THE THIRD, THE HEALING COMMUNITY STUDIES THAT FRANCIS WAS MENTIONING, AN OPPORTUNITY OF BEING BOLD AND SAYING WE HAVE ALL OF THIS EVIDENCE-BASED INTERVENTIONS, BUT IT HAS ALWAYS BEEN DONE IN ISOLATION. SO WHAT ABOUT TAKING IT TOGETHER, INTEGRATING IT, AND WHICH WILL FORCE THESE COMMUNITIES TO WORK, NOT JUST WITH THEIR CLASSICAL PEOPLE THAT THEY ARE WORKING ON, FORCE THEM TO WORK WITH JUSTICE SETTING WITH POLICE DEPARTMENT, WITH FAITH GROUP ORGANIZATIONS, WITH SUBSTANCE ABUSE TREATMENT, IN ITEMS OF AGENCIES FOR US TO WORK CLOSELY WITH SAMHSA, WITH JUSTICE DEPARTMENT, WITH THE STATE, TO BRING TOGETHER THIS EVIDENCE-BASED INTERVENTIONS IN A WAY WE CAN SHOW WE CAN REDUCE OVERDOSE MORTALITIES BY 40% IN THREE YEARS. CAN WE DO IT? I DON'T LIKE THE IDEA OF PUTTING NUMBERS LIKE THAT BECAUSE THEY CAN COME TO BIAS BUT IF YOU LOOK AT SOME TRACK RECORDS OF SOME COMMUNITIES THAT HAVE BEEN ABLE TO SHOW THEY CAN DO THIS MY ANSWER IS YES. WE CAN DO IT. I MEAN, CERTAINLY WE CANNOT CONTROL THE ENTRY OF CERTAIN DRUGS IN AN AREA WHICH COULD TURN THIS UPSIDE DOWN OR CHANGE THE WAY WE ARE REIMBURSING FOR THE TREATMENT OR SUSTAINING THIS TREATMENT BUT OVERALL BASED ON CONDITIONS THAT WE HAVE, THIS IS A DOABLE APPROACH. WE WANT TO SHOW IT, TO INSPIRE OTHERS, BECAUSE IF YOU CAN SEE THAT THESE INTERVENTIONS WORK THEN OTHERS CAN LEARN FROM IT. AND IN THE PROCESS BY THE WAY I THINK THIS COULD DO WONDERS FOR STIGMA BECAUSE IF WE CAN DEMONSTRATE THAT ULTIMATELY WE CAN TREAT IT, AND WE AS A COMMUNITY WORKING TOGETHER ARE SUPPOSED TO STIGMATIZE IT THEN AGAIN THAT WILL SERVE AS AN EXAMPLE TO OTHERS. THEN WE HAVE THE CONCEPT, ONE OF THE ASPECTS WE HAVE TO KEEP OUR EYES ON, HOW DO WE PREVENT HIGH RISK OF OPIOID USE DISORDER IN THE TRANSITION FROM ADOLESCENCE TO ADULTHOOD, AND FOR THAT PURPOSE WE'RE GOING TO WORKING WITH THE EDUCATIONAL SYSTEM, JUSTICE SYSTEM AND HEALTHCARE SETTING. IMPORTANTLY, ALSO RECOGNIZE, THIS IS SOMETHING THAT IS PREVALENT BOTH IN PAIN AS WELL AS IN ADDICTION, PRODUCES SIGNIFICANT DISRUPTION OF CIRCADIAN RHYTHM AND SLEEP PATTERN THAT CONTRIBUTE TO RELAPSE. PATIENTS CANNOT SLEEP AND TAKE DRUGS, RELAPSE TO OVERCOME IT. AS FRANCIS SAID, THESE QUESTIONS CAME OUT IN ONE OF THE MEETINGS, AND THEN GOT REITERATED IN OTHERS, HOW DO YOU TREAT SOMEONE THAT IS STARTING TO MISUSE OPIOIDS? DO YOU GIVE THEM BUPRENORPHINE? IS THAT JUSTIFIED? DO YOU GIVE THEM METHADONE? WE REALLY DO NOT HAVE THE EVIDENCE BASE TO ACTUALLY DETERMINE WHAT IS THE BEST INTERVENTION. YET IT'S IMPORTANT, EXTREMELY IMPORTANT, BECAUSE THERE ARE 30 MILLION PERSONS MISUSING OPIOIDS. THERE'S 2.4 WITH OPIOID USE DISORDER. 30 MILLION. SHOULDN'T WE KNOW BETTER HOW TO DEAL WITH IT? FRANCIS BRINGS THIS, I DON'T FORGET IT BECAUSE I'M A VERY OBSESSIVE PERSON BUT ON TOP OF THAT FRANCIS IS ALSO OBSESSIVE KEEPS ON SAYING, NORA, HOW LONG DO WE HAVE TO TREAT? BETSY ABOUT SPEAK ABOUT IT. IT'S A CHALLENGING QUESTION. THAT'S WHY I BASICALLY WHEN REBECCA CAME TO ME, NORA, WHAT DO YOU THINK WOULD BE MOST VALUABLE, THIS ONE WOULD BE THE MOST VALUABLE BECAUSE AS I HAVE THOUGHT INITIALLY AND I HAD TO CHANGE THE SLIDE A LITTLE BIT, RANDOMIZED CLINICAL TRIAL TO SEE HOW LONG DO WE DISCONTINUE, RAPIDLY THE EXPERTS COMING TOGETHER PUTTING THEIR HEADS REALIZED THIS WAS A MAGICAL THINKING TO THINK WE WOULD BE ABLE TO ADDRESS IT THAT WAY. SO THEY HAVE BEEN WORKING AT IT, I WANT YOU TO HEAR WHERE THEY ARE AT AND RECOGNIZE HOW TO GO ABOUT COMING, GETTING THIS INFORMATION THAT IS SO IMPORTANT IN GUIDING PATIENTS. COLLABORATIVE CARE MODEL, THIS IS SOMETHING THAT BEHOOVES US ACROSS THE HEALTHCARE SYSTEM. WE HAVE TO DEVELOP CARE MODELS THAT NOT ONLY ARE EFFECTIVE BUT SUSTAINABLE BECAUSE OTHERWISE IT BECOMES A PIE IN THE SKY. THEN THIS IS THE LAST SLIDE, WHICH I LOVE THIS SLIDE, IT'S A BABY AND ALWAYS MAKES ME SMILE TO SEE A BABY. I CHANGED THE TITLE TO IMPROVE OUTCOMES OF INFANTS WITH NEONATAL ABSTINENCE SYNDROME, OPIOID WITHDRAWAL, AND OPIOID AFFECTED FAMILIES. WE HAVE TO RECOGNIZE THAT IT'S NOT JUST THE ABSTINENCE SYNDROME BUT WHAT HAPPENS TO THE INSTANTS ONCE THEY GET DISCHARGED FROM THE HOSPITAL. THE ADVANCING CLINICAL TRIAL NEONATAL OPIOID WITHDRAWAL SYNDROME IS BEING LED BY MY COLLEAGUE DIANA BIANCHI TO MY LEFT, AND IT'S SOMETHING THAT WE HAVE AT NIDA BEEN WORKING ON FOR MANY YEARS, HOW DO WE DEVELOP BETTER MEDICATIONS AND CLEAR-CUT EVIDENCE THAT THERE'S BEEN SIGNIFICANT IMPROVEMENT BUT THERE'S MUCH MORE TO BE DONE. THE SECOND ONE IS HEALTHY BRAIN AND CHILD DEVELOPMENT STUDY, AND THIS IS TO ACTUALLY VERY AMBITIOUS, HOW ABOUT FOLLOWING, NOW THAT WE HAVE THE TECHNOLOGY, 10,000 INFANTS AS THEY TRANSITION FROM EARLY CHILDHOOD INTO ADOLESCENCE BY SYSTEMATICALLY AND REGULARLY MONITORING THEIR COGNITIVE BEHAVIORAL, SOCIAL, PHYSICAL, AND BRAIN DEVELOPMENT, WITH AMONG THEM AN OVERREPRESENTATION OF INFANTS THAT HAVE BEEN EXPOSED TO OPIOIDS BY THEMSELVES OR IN COMBINATION WITH ALCOHOL AND TOBACCO WHICH IS THE MOST COMMON PRESENTATION. IMPORTANTLY, HOW DO ADVERSE FAMILY ENVIRONMENTS AFFECT THAT DEVELOPMENT. AND THAT WILL ENABLE US TO UNDERSTAND IT BETTER SO WE CAN OF COURSE DO INTERVENTIONS TO REMEDIATE AND STRENGTHEN AND PROVIDE RESILIENCE TO THESE INFANTS. SO WE'VE DONE A LOT OF WORK BEHIND EACH ONE OF THESE INITIATIVES. AS FRANCIS WAS SAYING, MANY OF THEM ARE CURRENTLY REVIEWING, HEAL INITIATIVE IS ON ITS SECOND WEEK OF SITE VISITS, THIRD WILL BE NEXT WEEK. WE'VE HELD SEVERAL MEETINGS FOR THAT HEALING BRAIN AND CHILD DEVELOPMENT STUDY. JUSTICE SETTING. SO ALL OF THESE ARE ONGOING, AND WE -- AND THEY ARE BEING SEEN ALSO AS PROJECTS THAT ARE ALIVE, IN THAT EVEN THOUGH WE'RE FUNDING THESE INITIATIVES WE ARE KEEPING A CLOSE EYE AND HOPE WE CAN GET YOUR INPUT IN TERMS OF HELPING US IDENTIFY THE OPPORTUNITIES TO MAXIMIZE THE OUTCOMES OR TO IMPROVE THEM. WITH THAT I WANT TO THANK YOU FOR YOUR ATTENTION. >> THANKS, NORA. MAYBE WE SHOULD GO TO WALTER AND WE'LL HAVE TIME FOR DISCUSSION ABOUT BOTH OF THESE BUT IMPORTANT TO SEE HOW THEY FIT TOGETHER. WALTER, ARE YOU READY? >> THANK YOU. CONTINUING THE THEME, AS NORA MENTIONED, AND PROBABLY PEOPLE AROUND THE TABLE KNOW, ONE OF THE MAIN DRIVERS OF THE PROBLEM THAT WE HAVE NOW WAS THE OVERUSE OF OPIOIDS IN THE MANAGEMENT OF PAIN, AND I THINK THAT THE PEOPLE WHO PRACTICE MEDICINE AROUND THE TABLE REALIZE THAT THIS IS A SYMPTOM OF A BIGGER PROBLEM IN HEALTHCARE SYSTEM WHERE VERY DIFFICULT PATIENTS, IT'S SO MUCH EASIER FOR A PHYSICIAN TO WRITE A PRESCRIPTION THAN TO ACTUALLY, YOU KNOW, DO WHAT'S NECESSARY. UNFORTUNATELY WITH A PATIENT WITH CHRONIC PAIN, IT'S A VERY -- THE PATIENT NEEDS A LOT OF TIME TO GO THROUGH AND HELP THEM MANAGE THEIR ISSUES. AND SO THEY ARE REACHING FOR THE PRESCRIPTION, I THINK GOT US INTO THE PLACE WE ARE NOW, NORA MENTIONED THAT, YOU KNOW, IT'S A LITTLE BIT DIFFERENT NOW BUT IF WE WANT TO CHANGE THE PARADIGM LONG TERM WE THINK IT'S NECESSARY TO DEVELOP MORE EFFECTIVE PAIN TREATMENT IT'S, TO GIVE THE EVIDENCE TO PHYSICIANS AND HEALTHCARE SYSTEMS ON WHAT IS THE BEST MANAGEMENT OF PAIN AND TO DEVELOP NEW EFFECTIVE PAIN TREATMENTS THAT ARE NOT ADDICTIVE. THAT'S THE OVERALL GOAL OF THE PAIN SIDE OF THE HEAL INITIATIVE. SO, DELVING DOWN A LITTLE BIT, WE'RE INTERESTED IN UNDERSTANDING THE BIOLOGICAL UNDERPINNINGS OF CHRONIC PAIN TO MANIPULATE THOSE FOR HEALTH, AND THIS GOES FROM MOLECULAR TO BIOPSYCHOSOCIAL THAT LEADS TO THE BURDEN OF PAIN. WE'RE INTERESTED IN MOVING WHAT WE -- NIH HAS DONE AND IS STRONG SUIT, ACCELERATING DEVELOPMENTS TO COMMERCIALIZE FOR THE BENEFITS OF PATIENTS. WE'D LIKE TO TRY TO WHAT WE CALL DE-RISK THIS PIPELINE MOVING THINGS THROUGH FROM DISCOVERY TO COMMERCIALIZATION, AND ACCELERATE THE PROCESS AS BEST WE CAN, AND THEN THAT IS KIND OF THE LONG-TERM GOAL THAT WILL TAKE TIME BUT WE ALSO HAVE WHAT WE CONSIDER SHORT TERM WINS IN FUNDING RESEARCH THAT WILL ESTABLISH THE BEST PAIN MANAGEMENT STRATEGIES FOR ACUTE PAIN AND FOR NUMEROUS CHRONIC PAIN CONDITIONS, SO THE LAST WOULD GIVE EVIDENCE TO PHYSICIANS AND PATIENTS ON HOW BEST TO MANAGE THEIR PAIN CONDITION GIVEN THE CURRENT AVAILABILITY OF TREATMENTS. NOW, AT NIH, AS FRANCIS MENTIONED, PAIN RESEARCH IS SPREAD ACROSS ALMOST ALL OF INSTITUTES, A CONSIDERABLE FUNDING THAT'S BEEN GOING ON FOR MANY YEARS, AND I THINK HAS LED TO AN IMPROVEMENT, SIGNIFICANT IMPROVEMENT OR KNOWLEDGE OF HOW PAIN CIRCUITS WORK. AND THE HEAL INITIATIVE WILL BRING TOGETHER THE POWER OF ALL THE INSTITUTES TO WORK TOGETHER ON THIS PROBLEM AND THEN I THINK IN AND OF ITSELF IS A VERY FAVORABLE TURN BECAUSE WHEN THE INSTITUTES GET TOGETHER MAGIC CAN HAPPEN LIKE IT CAN'T IN OTHER WAYS. NOW, I WANT TO TALK QUICKLY ABOUT A SERIES OF PROGRAMS AND THESE AS I MENTIONED EARLIER, THEY SPAN FROM DISCOVERY SCIENCE THROUGH PRE-CLINICAL DEVELOPMENT, INTO CLINICL TRIALS AND THEN INTO IMPLEMENTATION, DISSEMINATION. AND SO WE HAVE I THINK KIND OF PUT FUNDING ACROSS THIS ENTIRE SPECTRUM TO LEAVE NO GAPS, BUT CERTAIN AREAS WILL CERTAINLY BE AREAS OF GREATER INVESTMENT THAN OTHERS. THE FIRST ONE AS WAS MENTIONED BY FRANCIS IS COMMON FUND PROJECT TO STUDY THE ACUTE TO CHRONIC PAIN SIGNATURES. AND THE IDEA HERE IS TO TRY TO GET SOME BIOSIGNATURES THAT IDENTIFY THE SUSCEPTIBILITY TO DEVELOPING CHRONIC PAIN AFTER AN ACUTE EVENT, OR ACTUALLY TO UNDERSTAND RESILIENCE, WHY DO SOME PEOPLE DEVELOP CHRONIC PAIN, OTHERS DON'T. IS IT THE TYPE OF INJURY? IS IT THE SUBSTRATE ON WHICH THE INJURY OCCURS? OR IS IT THE TREATMENTS THAT THEY ARE GETTING IN THE HOSPITAL? OR IN THE SHORT TERM THAT LEAD TO CHRONIC PAIN? THIS IS GOING TO BE INVOLVING THE PHENOTYPING, GENOTYPING, OMICS, OUTCOMES HOPEFULLY IN UNDERSTANDING MECHANISMS THAT GIVE RISE TO CHRONIC PAIN AFTER ACUTE EVENT, IF WE'RE REALLY LUCKY WE'RE HOPING SOME MECHANISMS WILL ALLOW TO US INTERVENE TO PREVENT CHRONIC PAIN FROM OCCURRING IN A HIGH RISK SITUATION. BUT EVEN IN THE SHORT TERM I THINK WE WILL LEARN A GREAT DEAL ABOUT WHO IS AT RISK FOR DEVELOPING CHRONIC PAIN AND INDIVIDUALIZE THEIR THERAPIES. AND THIS OF COURSE INCLUDES IDENTIFYING WHO IS AT GREATEST RISK FOR NEEDING OPIOIDS OVER THE LONG TERM AND DEPENDENCY. OKAY. THE NEXT SET OF PROGRAMS ARE ALL IN THIS PRE-CLINICAL DEVELOPMENT OF NON-ADDICTIVE PAIN TREATMENT SPECTRUM. AND THE FIRST OF THESE IS DISCOVER AND VALIDATE NOVEL TARGETS FOR SAFE EFFECTIVE PAIN THERAPY, SOMETHING THAT NIH HAS BEEN DOING FOR DECADES. AND IN FACT AS I MENTIONED THE SCIENCE OF PAIN HAS REALLY CHANGED OVER THE LAST I WOULD SAY TWO OR THREE DECADES TO IDENTIFY DIFFERENT STEPS IN THE PAIN CIRCUITS THAT ARE POTENTIALLY PLACES WHERE ONE MIGHT INTERVENE. AND THESE ARE MOLECULAR TARGETS BUT ALSO TARGETS OF THE CIRCUIT LEVEL. SO THIS RESEARCH WILL ENCOURAGE AND KIND OF ADVANCE THIS KIND OF DISCOVERY RESEARCH TO REVEAL NOVEL TARGETS FOR SMALL MOLECULES, NATURAL PRODUCTS, BIOLOGICAL DEVICES, WITH DEVICES WE THINK THAT -- I'LL TALK ABOUT THIS IN A SECOND, WE HAVE SOME REALLY VERY INTERESTING RESEARCH THAT WILL LEAD US TO TECHNOLOGIES THAT CAN MANIPULATE THE PAIN SYSTEM LIKE WE NEVER COULD BEFORE. AND THE SECOND PART OF THIS IS THAT IN ADDITION TO WHAT WE'VE PREVIOUSLY FOCUSED ON IS THAT ONE OF THE MAJOR BARRIERS IN GOING FROM BENCH TO BEDSIDE HAS BEEN THE VALIDATION OF TARGETS, SO IT'S PRETTY COMMON TO SEE A PAPER PUBLISHED KNOWING FIVE YEARS, WHAT HAPPENED TO THAT, WHERE DID IT GO, AND SO WE WILL INVEST ON VALIDATING TARGETS KNOWING HOW ROBUST IS THE EFFECT, HOW DOES IT GENERALIZE AMONG DIFFERENT PAIN CONDITIONS, IS IT REPRODUCIBLE? AND I THINK THESE ARE THE VALIDATION STEPS THAT WILL MOVE THINGS, REALLY PROMISING TARGETS TOWARDS THERAPEUTIC DEVELOPMENT. THE AREAS OF INTEREST WITH REGARD TO MANIPULATING THE CIRCUITS, ALSO USING CIRCUITS AS TARGETS THEMSELVES ARE THE TWO MAJOR PROJECTS GOING ON, ONE IS THE BRAIN INITIATIVE, WHICH IS BRAIN RESEARCH TO ADVANCE INNOVATIVE NEUROTECHNOLOGIES, SO THIS HAS REALLY CHANGED THE GAME IN MONITORING AND MODULATING BRAIN CIRCUITS, THIS CAN ALSO BE APPLIED TO SPINAL CORD CIRCUITS, AND WE'RE HOPING THAT THIS WORK IN FOCUSING ON PAIN WILL LEAD TO MUCH MORE EFFECTIVE WAYS OF ACTUALLY DIRECTLY INTERVENING THE CIRCUITS OR POTENTIALLY DEVELOPING SMALL MOLECULES OR BIOLOGICS BECAUSE THEY CHANGE THE CIRCUIT IN A BENEFICIAL WAY. AND ON THE PERIPHERAL SIDE, NIH IS ALSO FUNDING STIMULATING PERIPHERAL ACTIVITY TO RELIEVE CONDITIONS PROJECT WHICH SIMILAR TO BRAIN INITIATIVE IS FOCUSED ON PERIPHERAL NERVE MONITORING AND STIMULATION IN MULTIPLE CONDITIONS, AND, AGAIN, PERFECT SETUP TO USE THOSE TECHNOLOGIES FOR THE TREATMENT OF PAIN. WITH OUR PARTNERS IN THE NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCE, THERE'S A MAJOR PROGRAM GOING ON TO SUPPORT THE PRE-CLINICAL OPTIMIZATION AND DEVELOPMENT OF SAFE EFFECTIVE AND NON-ADDICTIVE THERAPIES BASED ON HUMANS CELL AND TISSUE MODELS, SO MUCH -- WE'LL TALK ABOUT THIS IN THE NEXT SLIDE AS WELL, THAT MUCH OF THE RELUCTANCE ON THE PHARMACEUTICAL COMPANIES TO BE INVOLVED IN PAIN HAS BEEN BECAUSE OF THE LACK OF CONFIDENCE IN ANIMAL MODELS THEY HAVE BEEN RELYING ON TO GO FROM TESTING IN ANIMALS AND THEN TO PATIENTS. THERE'S VERY MUCH INTEREST IN THE FACT THAT IF WE MOVE TOWARDS HUMAN CELLS, THAT SOME OF THIS PROBLEM WILL GO AWAY, AND SO THE NCATS HAS A VERY ROBUST PROGRAM USING iPS CELL DERIVED NEURONS, 3D PRINTED ORGANOIDS OR TISSUE CHIPS TO SCREEN FOR POTENTIAL PHENOTYPIC ACTION OF DIFFERENT MOLECULES THAT MAY BE IMPORTANT FOR PAIN. IT'S ALSO THESE TECHNOLOGIES ARE USEFUL IN ADVANCING INVESTIGATIONAL DRUGS FOR NEW TARGETS, SO NCATS HAS HUMAN TISSUE CONSTRUCTS TO IDENTIFY NEW PROBES, DRUG LEADS AS WELL AS TO LOOK AT SAFETY, AND THEY HAVE MEDICINAL CHEMISTRY, AUTOMATED CHEMICAL SYNTHESIS AVAILABLE TO MANIPULATE MOLECULES, TO IMPROVE THEIR ABILITY TO HIT YOUR TARGET, AND PROGRAMS THAT WILL BE AVAILABLE THROUGH NCATS AND ALSO THROUGH NINDS TO OPTIMIZE THE NON-ADDICTIVE THERAPIES. THESE ARE PROGRAMS TO DO THE -- THAT GO THROUGH STEPS NEEDED TO GET TO FDA APPROVAL TO GO INTO PATIENTS WITH IDE OR IND, SO SWITCHING TO THE NEXT PLATFORM IS THE ANIMAL PLATFORM SO I MENTIONED DIFFICULTIES IN THE PAST AND WE THINK THAT NIH CAN MAKE A MAJOR CONTRIBUTION BY SETTING UP A HIGH-QUALITY ANIMAL TESTING PLATFORM, AND WE WOULD BE REFINING ANIMAL MODELS OF PAIN CONDITIONS TO BETTER MIRROR WHAT OCCURS IN HUMANS AND TO CONTINUOUSLY LEARN ON HOW THE ANIMAL RESULTS PREDICT WHAT HAPPENS IN THE HUMAN, WHETHER IN A POSITIVE WAY OR NEGATIVE WAY, SO WE CAN HOPEFULLY HAVE A REAL CHANGE IN THE ABILITY TO FIND TREATMENTS THAT WILL MOVE FROM THE ANIMAL TO THE HUMAN. I MENTIONED THE DEVICE SPACE WE THINK IS REALLY OPEN FOR INNOVATIVE NEW TREATMENTS. CURRENTLY ELECTRICAL STIMULATION, SAY THE SPINAL CORD, FOR SOME PAIN RELIEF. IT'S QUITE CRUDE COMPARED TO THINGS COMING OUT OF THE BRAIN INITIATIVE AND SPARC INITIATIVE, THEY HAVE MORE PRECISION AND HOPEFULLY EFFECTIVENESS TO OFFER. AND VALIDATION IS IMPORTANT, BUT ONE OTHER THING THAT IS -- CHRISTINE MENTIONED THIS, IS THAT THERE IS A NEED FOR MOVING FROM THE ANIMAL INTO THE HUMAN TO HAVE THE RIGHT TYPE OF OUTCOME MEASURES. NOW, CLEARLY IN THE LATE PHASE STUDIES IT'S FUNCTIONAL OUTCOME THAT YOU'RE TRYING TO ACHIEVE. IN THE EARLY PHASE WE NEED BIOMARKERS OF TARGET ENGAGEMENT SO WHEN YOU GIVE A DRUG OR DEVICE AND YOU WORKED IT OUT ON THE ANIMAL, YOU KNOW WHAT YOU WANT TO DO, WHEN IT GOING INTO THE HUMAN DOES IT DO WHAT YOU WANTED IT TO DO? SO EVIDENCE OF TARGET ENGAGEMENT, PROOF OF PRINCIPLE, THESE THINGS WOULD BE VERY HELPFUL ESPECIALLY IN EARLY PHASE TRIALS TO KNOW VERY QUICKLY WHETHER YOUR DRUG OR DEVICE IS DOING WHAT YOU THINK IT'S DOING, SO YOU CAN EITHER FAIL FAST OR MOVE FORWARD MORE QUICKLY. SO A BIOMARKER EFFORT, IF SUCCESSFUL, COULD ALSO BE A SIGNIFICANT GAME CHANGER FOR THE FIELD. SO THESE ARE KIND OF WHERE WE ARE NOW. WE'RE DOWN TO THIS IDEA OF EARLY PHASE PAIN INVESTIGATION CLINICAL NETWORK, WHICH WE CALL EPPIC-Net. SO HAVING MOVED THROUGH THE PATHWAYS TO EARLY PHASE STUDIES, WE THINK THAT NIH CAN BRING VALUE TO THE TABLE BY SETTING UP A NETWORK OF SOPHISTICATED PAIN RESEARCHERS THAT CAN DO EARLY PHASE TESTING OF NEW TREATMENTS WITH DEVICES OR SMALL MOLECULES OR BIOLOGICS, AND TO LEARN, REITERATIVELY FROM SUCCESSING OR FAILURES AS THEY MOVE ALONG. MUCH OF THE RESEARCH IN THE PAIN AREA IS DONE BY CROs WITH SPECIFIC CHARGE TO THEM, BUT WE THINK THAT DEEP PHENOTYPING OF PATIENTS, SOMETHING THAT CAN BE DONE IN THE UNIVERSITY SETTING BETTER, THE USE OF BRINGING IN BIOMARKERS TO STUDY PAIN CONDITIONS, IN THE SETTING OF A TREATMENT CAN BE DONE MUCH BETTER IN THIS TYPE OF AN ENVIRONMENT. AND HOPEFULLY WE CAN AGAIN DE-RISK WHAT WE CALL ASSETS WHICH CAN COME IN FROM COMPANIES, FROM ACADEMIA. THE IDEA IS OPEN DOOR PROCESS FOR SUBMITTING ASSETS FROM INDUSTRY OR ACADEMIA. THESE ASSETS WILL BE PRIORITIZED BY A STUDY SECTION WITHIN NIH, WITH JUST THE SAME KIND OF CONTROL, WE HAVE ON ALL STUDY SECTIONS, AND THAT THE MOST PROMISING OF THE ASSETS WILL THEN BE WORKED ON BY THE CLINICAL TRIAL NETWORK WITH THE OWNER OF THE ASSET TO BUILD A PHASE 2 CLINICAL TRIAL, THE PURPOSE OF WHICH WILL BE TO SEE IF THAT ASSET HITS THE CRITERIA TO GO TO PHASE 3. THIS IS KIND OF A CORE OF THE PAIN PROGRAM FOR THE PRE-CLINICAL DEVELOPMENT. AND, AGAIN, IT REQUIRES, AS YOU CAN IMAGINE FOR THIS TO BE SUCCESSFUL, WE HAVE TO BE WORKING WITH A PARTNERSHIP WITH THE INDUSTRY SIDE BECAUSE WE DON'T WANT TO BECOME A PHARMACEUTICAL COMPANY. WE WANT TO DE-RISK SO THAT AFTER EPPIC-Net THESE THINGS CAN GO TO PHASE 3s, RUN BY THE COMPANIES, AND BECOME COMMERCIALIZED. WE HAVE A COUPLE OF PAIN AREAS THAT HAVE BEEN IDENTIFIED, AS SPECIAL NEED. AND THE FIRST OF THESE IS BACK PAIN RESEARCH CONSORTIUM, KNOWN AS BACPAC. THE U.S. BURDEN OF DISEASE COLLABORATORS PUBLISH ON A REGULAR BASIS WHAT ARE THE MAJOR CAUSES OF U.S. YEARS LIVED WITH DISABILITY, AND NUMBER ONE IS BACK PAIN. IT HAS BEEN BACK PAIN FOR OVER 20 YEARS, ABOVE DEPRESSION AND DIABETES, TWO AND THREE. NUMBER FOUR IS OTHER MUSCULOSKELETAL DISORDERS, THAT COMES ABOVE MIGRAINE, NUMBER FIVE. ABOVE NECK PAIN, NUMBER SIX; ABOVE OPIOID ABUSE. THESE ARE MAJOR CAUSES OF DISABILITY WHICH WE VERCHT FOCUSED ON, AND NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL DISEASE, BOB CARTER IS HERE, COORDINATING WITH EPPIC-Net. THE NET AREA THAT'S BEEN PULLED OUT -- LET ME JUST GO IN ORDER OF SLIDES. NOW GETTING TO THE RESEARCH THAT WILL INFORM PHYSICIANS AND PATIENTS ON THE BEST TREATMENT IS A CALL FOR RESEARCH IN PAIN, AS YOU CAN SEE MOST OF THE WORK THAT WE'RE DOING IS WE HAVEN'T CHOSEN EXCEPT FOR THE BACK PAIN AND WE'LL TALK ABOUT HEMODIALYSIS PAIN, IT'S OPEN TO WHAT OPPORTUNITIES ARE AVAILABLE FOR THE BIGGEST IMPACT SO THE PAIN CONDITION IS NOT PRESCRIBED BUT THERE'S A CALL FOR STUDIES, THIS NETWORK WILL BE RUN IN COLLABORATION WITH NATIONAL CENTER FOR ADVANCEMENT OF TRANSLATIONAL SCIENCES, I SEE JANE OVER. THERE JANE ATKINSON FROM NCATS AND LINDA PORTER FROM NINDS. I THIS WILL COORDINATE CLINICAL RESEARCH AND ALSO I THINK BRING PAIN TO A HIGHER PROFILE WITHIN THE POWERFUL RESEARCH THROUGH THE NETWORKS THE CPSAs ENCOMPASS. THIS IS HEMODIALYSIS, THE OTHER CONDITION CYCLED OUT FOR CALL FOR GRANTS. PAIN IS A MAJOR PROBLEM IN HEMODIALYSIS, 64% OF PEOPLE UNDERGO HEMODIALYSIS, RECEIVE OPIOIDS, 23%, ONE HIGH DOSE PRESCRIPTION, METABOLISM CHANGED BY RENAL FAILURE AND HEMODIALYSIS, UP AND DOWN IN TERMS OF WHAT DOSE THE PATIENT IS SEEING, THIS HAS LED TO CHANGES IN MENTAL STATUS, FALLS AND FRACTURES. THEY HAVE SPECIAL HEADACHE, A BIG PROBLEM, DUE TO FLUID SHIFTS, MUSCULOSKELETAL A BIG PROBLEM, IDENTIFIED AS AREA OF HIGH UNMET NEED WHERE HEAL INITIATIVE CAN MAKE A BIG IMPACT. FINALLY AT THE END IMPLEMENTATION RESEARCH, IT'S THE BEGINNING OF THE WORK THAT WORK TO CHANGE THE HEALTHCARE SYSTEM THROUGH HELEN, GROUP AT NCCIH, AND THE COLLABORATORY THEY HAVE ESTABLISHED, AND THEY ARE ALSO WORKING ON A MAJOR EMPHASIS FOR THE PRISM PROGRAM. WITH THAT, EPIDEMIC END WITH THE SLIDE AGAIN SHOWING ALL THE DIFFERENT THINGS. THERE ARE MANY INSTITUTES TAKING PART. IT REALLY IS AN OPPORTUNITY TO ADVANCE PAIN THERAPY, AND WE STAND READY TO TAKE FULL ADVANTAGE OF THIS. >> THANKS, WALTER. MIND BOGGLING IS THE THEME OF THE MORNING. WE'VE DONE IT AGAIN. REACTIONS ABOUT WHAT YOU'VE HEARD FROM NORA AND WALTER? WE'RE GOING TO NEXT GO INTO FIVE OF THESE IN MORE DETAIL. YOU'VE SEEN THE BIG LANDSCAPE REVEAL. COMMENTS OR QUESTIONS? >> A COMMENT AND QUESTION. VERY EXCITING, THE WORK AND PLANS. I DIDN'T HEAR SPECIFICS BUT IT WILL BE VERY IMPORTANT TO MAKE SURE THAT WE INCORPORATED THE HEALTH EQUITY LENS ON THE BEGINNING RATHER THAN GETTING DOWN THE ROAD AND TRYING TO TAILOR PARTICULAR INTERVENTION TO DIFFERENT COMMUNITIES, DIVERSITY OF COMMUNITIES, IT'S IMPORTANT AT THE BEGINNING THAT THAT IS SET AS A MARKER, WE'LL HAVE A FOUNDATION TO MAKE SURE HEALTH EQUITY LENS IS THERE. A SUBSET WOULD BE WHAT I CALL A CONCERN AROUND MIDDLE CLASS SOLUTIONS WHICH SOMETIMES WE GET TO, AN EXAMPLE, TALKING ABOUT FEATURE ON THE -- TALKING ABOUT PHYSICAL THERAPY ON THE WAY HERE, MY TOOLS MY BE A CONSIDERATION OF OPIOID PRESCRIPTION OR PHYSICAL THERAPY. ON THE SURFACE THEY SEEM EQUITABLY AVAILABLE BUT THEY ARE NOT BECAUSE PHYSICAL THERAPY MAY REQUIRE A VISIT THREE TIMES A WEEK WHICH COULD MEAN THREE CO-PAYS, YOU KNOW, CO-INSURANCE, OFTEN TRANSPORTATION, PERHAPS PAID TIME OFF FROM WORK. WE GET TO SOLUTIONS THAT SEEM EQUITABLE BUT IN PRACTICE THEY ARE NOT EQUITABLY AVAILABLE SO I THINK IT'S IMPORTANT TO AGAIN JUST SHINE A LIGHT ON THE NEED FOR THE HEALTH EQUITY LENS AT THE BEGINNING, AND RATHER THAN THE END OF THE PROCESS. >> GREAT POINT. >> KNOWN IF ANYONE -- I DON'T KNOW IF ANYONE HERE IS REPRESENTING THE HEALTHCARE SYSTEM. HER POINT HIGHLIGHTS AN ISSUE, IF THAT CO-PAY IS A BARRIER, REGARDLESS OF WHAT MODALITY MIGHT HAVE BEEN CHOSEN, HOW DO WE DEAL WITH THAT? BECAUSE EVEN IF THE BEST SCIENCE SAYS THAT'S THE WAY TO GO, IF WE CAN'T GET OUR PATIENT TO X, Y OR Z, IT WILL NOT HAVE THE IMPACT YOU'RE HOPING TO HAVE. SO HEALTH CARE ADMINISTRATORS NEED TO BE HERE AT THE TABLE BECAUSE THEY NEED TO SET UP THESE SORTS OF CLINICS AND OPTIONS. >> POINT TAKEN. AGAIN, I MENTIONED WE HAVE A CLOSE RELATIONSHIP WITH CMS IN THAT REGARD, WITH LEADERSHIP FORUM I CO-LEAD WITH SEEMA VERMA, AND WE SPEND A LOT OF TIME TALKING ABOUT WAYS IN THIS SPACE REIMBURSEMENT COULD BE BETTER ADAPTED TO THE NEED BECAUSE IT'S NOT RIGHT NOW, ESPECIALLY WHEN IT COMES TO MANAGEMENT OF CHRONIC PAIN. CMS WILL COME BACK AND HAMMER ON, WELL, WE'RE NOT GOING TO REIMBURSE FOR SOMETHING UNLESS YOU SHOW US EVIDENCE IT CHANGES OUTCOMES. THAT'S A LOT OF WHAT I THINK THESE PROGRAMS SHOULD BE TRYING TO DO AND WE SHOULD THINK ABOUT HOW WE'RE FUNDING THESE IN THE FASHION WOULD THIS PRODUCE THE KIND OF EVIDENCE CMS WOULD SAY, OKAY, NOW YOU'VE CONVINCED US, NOW WE'LL START TO REIMBURSE FOR THAT KIND OF INTERVENTION. I WOULD HAVE THOUGHT BY NOW EVIDENCE WOULD BE CONVINCING ENOUGH THAT NON-PHARMACOLOGICAL INTERVENTIONS FOR CHRONIC PAIN WOULD HAVE BEEN TO THE POINT WHERE THEY COULD BE REIMBURSED, MOSTLY THAT'S NOT THE CASE. AND AGAIN IT DEPENDS ON THE EYE OF THE BEHOLDER, IT LOOKS LIKE THERE'S PRETTY STRONG EVIDENCE BUT NOT STRONG ENOUGH, THEIR DEFAULT IS TO SAY NO, BECAUSE THEY ARE TRYING NOT TO SPEND ANY MORE MONEY THAN THE VAST SUMS ALREADY THERE ARE ALREADY SPENDING. THERE'S A LOT MORE THAN CMS BUT CMS HAS A BIG INFLUENCE ON WHAT THE REST OF THE HEALTH SYSTEM DECIDES THEY WILL PAY FOR. >> IF I MAY PROJECT, ONE OF THE OPPORTUNITIES THAT'S WHY I SAY WITH "HEAL" WE MAY BE ABLE TO CHANGE THIS THROUGH THE HEALING COMMUNITIES, CMS HAS AN INNOVATION FOUND IDENTIFY UNIQUE RESOURCES FOR THINGS THEY NORMALLY PAY. ONE OF THE BIG CHALLENGES PEOPLE WITH OPIATE ADDICTION HAVE IN URBAN CENTERS IS HOMELESSNESS, WITHOUT THE HOME THEY CAN NOT GO TO TREATMENT. THIS IS AN OPPORTUNITY IN THE TYPE OF EVIDENCE THAT WE CAN BUILD SO THAT YOU CAN ULTIMATELY CHANGE PRACTICES. AS WE DEPLOY THE HEALING COMMUNITIES I THINK IT'S GOING TO BEHOOVE US TO LISTEN TO OPPORTUNITIES TO MAKE CHANGES SO THINGS ARE EQUITABLE AND WE HAVE REIMBURSEMENT FOR THINGS NORMALLY NOT COVERED. >> I WAS GOING ADD THAT I AGREE WITH YOU. I'VE BEEN TO MANY MEETINGS WITH CMS, SHARI LING WILL TELL YOU IT'S NOT JUST 65 AND OLDER BUT COMORBID CONDITIONS, IT'S ALSO IMPORTANT TO UNDERSTAND THE POPULATIONS THAT WE'RE RESEARCHING, AND ROUTINELY IN CLINICAL TRIALS WE SEE PATIENTS THAT DON'T NECESSARILY RESEMBLE WHAT WE SEE IN REAL WORLD SETTINGS. AND TO UNDERSTAND HOW IMPORTANT THAT IS IN TERMS OF CHANGING REIMBURSEMENT PRACTICES AS WELL. THE OTHER ISSUE THAT I SEE NOT HERE IS AGAIN THE WORKFORCE, INSUFFICIENT WORKFORCE ON THE ADDICTION SIDE AND PAIN SIDE. AND THERE'S A REAL NEED FOR TRAINING OF INDIVIDUALS, ALSO TRYING TO ATTRACT PEOPLE INTO THIS AREA. I WAS IN A MEETING LAST YEAR WITH PATIENTS WITH PAIN, PARKINSON'S, M.S., EACH WROTE WHAT THEIR EXPERIENCE WAS, WHAT THEIR PAIN FELT LIKE. AT THE END OF THE DAY WE HAD AN ENTIRE WALL COVERED. THIS PATIENT WITH PARKINSON'S SAID WHY WOULD ANY DOCTOR WANT TO GO INTO THIS? IT'S SO COMPLICATE AND COMPLEX. IT'S NOT VERY CLEAR HOW I ACTUALLY HELP SOMEONE IN THIS SITUATION. SO, WE DEFINITELY NEED TO ADDRESS THAT TRAINING ISSUE AS WELL, AND JUST QUICKLY WANT TO SAY I NEGLECTED TO THANK YOU, DR. BAKER, AS WELL EARLIER. I'M GOING, OH, NO, I DIDN'T! YOU'VE BEEN A PLEASURE TO WORK WITH AND VERY INVITING, INCLUSIVE AND PROFESSIONAL AND I APPRECIATE YOUR LEADERSHIP WITH THIS. >> HEAR, HEAR. YES? >> JUST AS WE'RE HAVING THESE CONVERSATIONS I KNOW THERE'S BEEN A TREMENDOUS AMOUNT OF EMPHASIS ON PREVENTION AND TREATMENT, AND I WANT TO MAKE SURE WE'RE THINKING ABOUT RECOVERY. SO HOW DO PEOPLE LIVING WITH CHRONIC PAIN AND/OR SUBSTANCE USE DISORDER IN PARTICULAR OPIOID USE DISORDER WHICH IS THE FOCUS TODAY, HOW DO WE HELP PEOPLE STAY WELL, AND AGAIN PUSHING CMS FOR RECOVERY ORIENTED SYSTEM OF CARE AND I KNOW NORA WITH YOUR HEALING COMMUNITIES YOU'RE GOING TO GET AT THAT BUT SO IF WE CAN START USING THAT LANGUAGE BECAUSE TREATMENT IS DISTINCT FROM RECOVERY. AND SO HOW DO WE HELP PEOPLE STAY WELL? AND CONTINUE TO INFUSE THE HOPE THAT PEOPLE DO GET WELL AND DO STAY WELL? >> OTHER OF ANOTHER GREAT POINT. YES, JUDITH? >> THANK YOU FOR ALL THIS AMAZING WORK IN THESE EXCELLENT PRESENTATIONS. NOT TO BE PROVINCIAL BUT DOES THE NCI HAVE A SEAT AT THE TABLE? TWO EXAMPLES, ONE IS NOT EXACTLY NEONATAL ABSTINENCE SYNDROME BUT I THINK ABOUT THE CHILDREN WITH PEDIATRIC CANCERS WHO HAVE BEEN EXPOSED TO OPIOIDS, THEY HAVE SLEEP DISORDERS, THEY HAVE KIND OF A PTSD FROM THE MEDICAL TREATMENTS THAT WE'VE INFLICTED, THEY MAY BE A GROUP THAT SHOULD BE STUDIED FOR SOME OF THE BIOMARKERS AND WE ALREADY HAVE CLINICAL TRIAL GROUPS IN ONCOLOGY THAT MIGHT FACILITATE SOME OF THOSE KINDS OF STUDIES, SECONDLY WITH OUR ADULTS WHO ARE BEING TREATED FOR CANCER AS WELL SIMILAR CLINICAL TRIAL EFFORTS, WE NEED TO USE OPIOIDS FOR SOME OF THESE INDIVIDUALS, FOR SOME OF THE PAIN SYNDROMES, AND SOME OF THE PAIN SYNDROMES WE CAN EVEN PREDICT AND FOLLOW. AND MAYBE EVEN PREVENT. SO JUST A THOUGHT. THANK YOU. >> WE SHOULD SAY THROUGH EFFECTIVENESS RESEARCH NETWORK HAD A PROGRAM WOULD WORK WITH NCI CLINICAL TRIALS BUT IT'S IMPORTANT TO CONTINUE TO DISCUSS IT. >> YES? >> SO A COUPLE POINTS. ONE TO FOLLOW UP ON PAIRED ISSUES AND HOW COMPLEX THAT CAN GET, WE HAVE A BIG PCORI STUDY LOOKING AT A NATURAL EXPERIMENT IN OREGON WHERE MEDICAID IS CHANGING WHAT THEY ARE REIMBURSING, NON-PHARMACOTHERAPY AND RESTRICTING CONVENTIONAL CARE. PAYMENTS ARE AVAILABLE FOR PEOPLE WITH BACK AND NECK PAIN, TREATMENT ENVIRONMENT, HAVING PROVIDERS AVAILABLE, PHYSICIANS KNOWING HOW TO HAVE THOSE CONVERSATIONS, THINGS ABOUT IMPLEMENTING THAT WORK THAT WE'RE FINDING COMPLICATED. THE OTHER THING I WANTED TO BRING UP, I WAS REALLY IMPRESSED WITH THE COMPREHENSIVENESS OF THE INITIATIVE, AND I WILL ALSO SAY, MAYBE PART IS BEING IN WASHINGTON STATE, BUT THE NUMBER OF -- WE LOOK AT WHAT PATIENTS ARE ACTUALLY USING, WHAT THEY ARE REPORTING, THE AMOUNT OF CANNABIS AND CBD USE AND NUMBER OF DOCS SAYING WE DON'T KNOW WHAT TO SAY TO OUR PATIENTS, THEY ARE USING THESE AGENTS, AND HOW QUICKLY THAT IS ALL CHANGING THE TYPES OF PREPARATIONS PATIENTS ARE USING, AND DISCONNECT, IT SEEMS STILL BETWEEN WHAT'S AVAILABLE THROUGH NIST SITE AND CBD PREPARATIONS AND WHAT'S IN THE COMMUNITY, A STICKY WICKET WITH DEA BUT IT FEELS LIKE A REAL UNCONTROLLED EXPERIMENT GOING ON, AND SOMETHING THAT WE REALLY NEED DATA ABOUT. >> GOOD POINT. ONE MORE QUESTION OR TWO AND WE SHOULD MOVE ON. YES? >> ONE THING THAT I SAW ON THE NORA'S SLIDES ABOUT NEW MEDICATIONS OUTCOMES, AND IN DRUG DEVELOPMENT IT'S GOING TO BE ABSOLUTELY ESSENTIAL THAT WE PARTNER WITH THE FDA, TO GO FAR BEYOND ABSTINENCE AND RETENTION IN TREATMENT, ANYTHING RELATED TO CRAVING, SLEEP DISORDER, DEPRESSION, ANXIETY, WILL BE ESSENTIAL. WE NEED A WORK GROUP TO PERHAPS MAKE A CASE TO COME UP WITH CREATIVE NEW CLINICAL OUTCOMES IN SUBSTANCE USE DISORDER OR TREATMENT. >> SCOTT GOTTLIEB HAS INDICATED AN OPENNESS TO THAT CONVERSATION. SO IT'S TIMELY INDEED. LAST QUESTION, YES? >> I JUST WANTED TO RAISE A QUESTION IN RESPONSE TO SOMETHING YOU SAID, DR. COLLINS, ABOUT NON-PHARMACOLOGICAL TREATMENTS FOR PAIN. MY READ ON THE LITERATURE IS SIMILAR TO YOURS THAT IT SEEMS WE HAVE EVIDENCE. SO I KNOW THERE'S LESS EVIDENCE IN TERMS OF THE BEHAVIORAL SIDE FOR OPIOID USE DISORDER, AND THAT'S PART OF THE INTENTION IN THIS PROCESS TO BUILD MORE OF THAT EVIDENCE. BUT SO THE QUESTION IS WHAT DO WE NEED TO DO THEN UNDER THESE CIRCUMSTANCES WHERE THERE ARE ACTUALLY DECADES OF EVIDENCE FOR THE EFFICACY OF NON-PHARMACOLOGICAL FOR CHRONIC PAIN, WHAT MORE TO FACILITATE THIS TRANSLATION? WE COULD FIND OURSELVES GENERATING EVIDENCE FOR EFFICACIOUS NEW TREATMENTS AND STILL SLOW UPTAKE DESPITE ALL THIS WORK WE'VE DONE. THAT'S JUST A QUESTION FOR ALL OF US. >> IT'S A VERY APPROPRIATE QUESTION. IT'S ONE THAT WE ARE POSING TO OUR COLLEAGUES AT CMS. IF YOU DON'T HAVE ENOUGH DATA WHAT WOULD IT TAKE AND LET'S BE SURE WE'RE DESIGNING FOLLOW-UPS HERE TO GENERATE THAT KIND OF EVIDENCE AND THEN YOU CAN'T SAY WE DIDN'T GIVE IT TO YOU. THIS IS A GOOD DISCUSSION. AND I HOPE WE HAVE A LANDSCAPE OPPORTUNITY, WE CAN BEGIN TO DRILL DOWN INTO THE FIVE AREAS THAT WE THOUGHT WOULD BE PARTICULARLY APPROPRIATE TO HEAR ABOUT TODAY, AGAIN NOT THAT WE'RE AT THE POINT OF MAKING ACTUAL DECISIONS BUT IT WILL BEGIN TO GET YOU INFORMED ABOUT THE KINDS OF THINGS WE'RE GOING TO BE ASKING YOU ABOUT LATER ON IN THIS COURSE OF THE VERY BUSY YEAR. WE'LL START WITH BETTY TAI. WE'VE MENTIONED CRITICAL NEED TO UNDERSTAND MORE ABOUT THE OPTIMAL LENGTH OF MEDICATION TREATMENT FOR OPIOID USE DISORDER, AND HOW IMPORTANT IT IS TO HAVE BETTER ANSWERS TO THAT. THIS IS NOT A TRIVIAL KIND OF QUESTION TO DESIGN A RESEARCH STUDY TO ADDRESS BUT YOU'LL HEAR WHERE WE ARE. WITH EACH OF THESE FIVE TOPICS WE'VE ASKED THE PRESENTERS TO SPEAK FOR ONLY 15 MINUTES, GIVING US PLENTY OF TIME FOR DISCUSSION, SO WE'LL TRY TO LIVE UP TO THAT. WITH THAT LET ME TURN IT OVER TO DR. TAI. >> GOOD MORNING. I'LL START HERE, WE DON'T HAVE A MICROPHONE OVER THERE. SO, I WILL CONTINUE THE PRESENTATION WITH MORE DRILLED DOWN EXPLANATION OF ONE OF THE RESEARCH TOPICS THAT NORA HAS MENTIONED EARLIER. IN FACT, DR. COLLINS ALSO MENTIONED EARLIER. THIS IS ABOUT OPTIMUM LENS OF DRUG USE MEDICATION TREATMENT. I DIRECT NIDA'S CLINICAL TRIALS NETWORK. SO, WHAT IS CTM? ENTERPRISE, CLINICAL RESEARCH INFRASTRUCTURE TO UNITE MEDICAL AND SPECIALTY TREATMENT PROVIDERS, RESEARCHERS, PATIENTS, AND PATIENT FAMILIES AND NIDA, NIH. WE STARTED THIS TO IMPROVE THE NATION'S ADDICTION TREATMENT USING THE SCIENCE-BASED TREATMENT PREVENTION INTERVENTION. IT HAS BEEN OUT THERE FOR A WHILE SINCE OCTOBER 1999 TILL NOW. THE APPROACH, THE STRATEGY TO CONDUCT RIGOROUS MULTI-SITE CLINICAL TRIALS TO DETERMINE EFFECTIVENESS OF TREATMENTS IN BROAD RANGE OF TREATMENT SETTINGS AND DIVERSE PATIENT POPULATIONS, WE INTEND TO DISSEMINATE IN A TIMELY FASHION TO CLINICIANS, PROVIDERS, THEIR PATIENTS AND FAMILIES. THIS IS THE DIAGRAM SHOWING OUR RESEARCH NODE, REGIONAL RESEARCH AND TRAINING CENTERS, CONCENTRATED ON THE COAST WITH A FEW ON THE CONTINENT. IT DEPENDS ON STUDY AND KIND OF PATIENT AND STRATEGY AND WHETHER THERE'S A GEOGRAPHIC FACTOR IMPACTING THE RESEARCH. WE DO HAVE FOR INSTANCE OHIO VALLEY NODE DOES HAVE LINKAGE TREATMENT PROVIDERS IN KENTUCKY, INDIANA, WEST VIRGINIA, IN PENNSYLVANIA. IT IS SOMEWHAT DISTRIBUTED NETWORK, GIVEN MORE RESOURCES I THINK WE CAN REALLY ENRICH THIS NETWORK. SO HERE I WANT TO DIVE IN, DIVE DOWN TO EXPLAIN THE RATIONAL AND THOUGHT BEHIND THE STUDY, AND ALSO THE DESIGN AND STRATEGY APPROACH WE USE TO DEFINE THIS RESEARCH STUDY. RIGHT NOW IT'S CALLED RETENTION DISCONTINUATION STUDY, WHICH IS TWO PHASE RANDOMIZED CONTROL TRIALS, HAS A PHASE 1, PHASE 1 WE WANT TO STUDY HOW TO BEST RETAIN PATIENTS IN TREATMENT IN MEDICATION TREATMENT, TO REDUCE DROPOUT, OUTCOME MEASURES IS RETAINING FOR SIX MONTHS. AND THEN THERE'S A SECOND PHASE CALLED DISCONTINUATION PHASE, OF THE RETAIN PATIENT BASICALLY TO STUDY HOW WE CAN BEST DISCONTINUE MEDICATION, RETAIN PATIENT THAT WOULD MINIMIZE THE RISK OF RELAPSE AND MINIMIZE RISK OF THE BAD CONSEQUENCES DUE TO RELAPSE OF OUD. WE ARE GOING TO GOING TO STUDY STRATEGY HOW TO TAPER PATIENT FROM MEDICATION AND STUDY MORE IMPORTANTLY I HEAR A LOT OF DISCUSSION THIS MORNING IS THE ROLE OF SUPPORTIVE COUNSELING IN TREATING MANAGING THE PATIENTS, OUTCOME MEASURE IS NO RELAPSE WITHIN SIX MONTHS OF DISCONTINUATION. I WANT TO EXPLAIN THE THOUGHT AND EFFORT BEHIND THIS, TREATMENT DISCONTINUATION INSTEAD OF STUDYING THE OPTIMIZED DURATION OF MOUD TREATMENT. WHEN WE WERE BESTOWED WITH THIS RESEARCH ASSIGNMENT BACK IN NOVEMBER 2018 WE IMMEDIATELY TWO THINGS. ONE TO ISSUE RFI, AND THE OTHER IS TO CONVENE AN EPSCoR PANEL IN NOVEMBER TO REACH OUT TO RESEARCH IN THE PROVIDER COMMUNITY TRYING TO SOLICIT THE WIDEST INPUT FROM THE COMMUNITY, AND TO TELL US HOW THEY THINK THIS CAN BE TARGETED, HOW TO MOST EFFECTIVELY ADDRESS THE RESEARCH QUESTION? WE RECEIVED QUITE A BIT OF RESPONSES, WE'VE HEARD IT WITH IMPROVE TREATMENT RETENTION AND REDUCE BAD CONSEQUENCES. WE ALSO LEARNED THAT WHETHER IN CLINICAL TRIAL OR CLINICAL TREATMENT THERE'S HIGH DROPOUT RATE, AT LEAST 40 TO 50% DROPOUT IN THREE TO SIX MONTHS. AND THESE DROPOUT PATIENTS ARE GUARANTEED ALMOST TO 80 TO 90% TO RELAPSE. AND IF WE ARE GOING TO DO A RANDOMIZED CONTROL TRIAL TO STUDY DURATION OF WHEN THEY ARE DROPPING OUT, THE OPTIMUM, WE FACE ETHICAL AND SAFETY CHALLENGES. I'LL EXPLAIN MORE TO YOU LATER ON. WE'RE CURRENTLY NOT VERY WELL INFORMED HOW TO RETAIN PATIENTS IN TREATMENT OR HOW CAN THEY BE SUCCESSFULLY DISCONTINUED THE TREATMENT. WE REVISED RESEARCH QUESTION HOW TO ENHANCE RETENTION AND SAFELY DISCONTINUE MEDICATION ONCE A PATIENT HAS SO DECIDED. IN OTHER WORDS WHEN THEY ARE OUT OF THE TREATMENT, THEY DECIDED TO DISCONTINUE THE TREATMENT, WE WANT TO IDENTIFY WHO ARE THESE PATIENTS, AND ALSO IDENTIFY WHAT WOULD BE THE BEST APPROACH TO MINIMIZE THE RISK OF RELAPSE, AND HOW CAN WE CAPTURE THEM IN TIME IF THEY RELAPSE, BECAUSE THE RELAPSE CONSEQUENCES ARE DIRE. HERE I'M EXPLAINING WHY DOING A RANDOMIZED CONTROLS TO DETERMINE THE OPTIMUM TREATMENT DURATION IS CHAN BE. -- CHALLENGING. THERE'S HIGH RELAPSE RATE WITH MEDICATION DISCONTINUATION. CONSEQUENCES OF RELAPSE ONCE THEY DISCONTINUED MEDICATION TREATMENT IS DIRE. THE CONSEQUENCES ARE DIRE. THEY INCLUDE OVERDOSE, ESPECIALLY WHEN THEIR TOLERANCE WAS REDUCED, AND OVERDOSE CAUSES MORTALITY. AND HIV HCV TRANSMISSION AND INFECTION, SOCIAL AND CJS, CRIMINAL JUSTICE CONSEQUENCES, ALL THESE CONSEQUENCES ARE SEVERE. AND COULD LEAD TO MORTALITY. AND WE HAVE VERY LITTLE KNOWLEDGE IN THE RESEARCH TO DEMONSTRATE HOW TO BEST HELPING PATIENTS TO DISCONTINUE IF THEY SO DO WISH TO. THE ADDICTION TREATMENT FIELD LARGELY FEEL THAT RECOGNIZE THAT I DON'T THINK WE HAVE ROBUST EVIDENCE IN SUGGESTING THAT IS THAT PATIENT MUST BE KEPT ABSTINENT IN TREATMENT AT LEAST THREE TO FIVE YEARS, STABILIZE THE PATIENT, THEY ALSO HAVE DEVELOPED GOOD SOCIAL FUNCTIONING AND IMPROVE THEIR QUALITY OF LIFE TO BEGIN TO CONSIDER THE DISCONTINUATION. AND ALSO, THERE IS A LOT OF DATA TO SUPPORT, IT IS FOR THE PATIENT'S BEST INTEREST TO RECOMMEND OR ENCOURAGE THEM TO DISCONTINUE THE MEDICATION TREATMENT. THAT BEING SAID, MANY PATIENTS CHOOSE TO DISCONTINUE ON THEIR OWN. SO, IT IS RESEARCH QUESTION THAT NEEDS TO BE ANSWERED BADLY, AND THE INFORMATION IS LACKING OUT THERE. AND MANY OF THE RESEARCHERS, RESEARCH COMMUNITY, ALSO SUGGEST THAT MAXIMUM OPTIMUM DURATION OF TREATMENT IS IMPORTANT QUESTION BUT THAT CAN BE OBTAINED BY DOING LARGE DATA BASE MINING. WE TALKED ABOUT CMS DATA AND WE ALSO HAVE PROPOSAL ON TABLE SUGGESTING THAT TO USE THE FDA MINI SENTINEL, POST-MARKETING DATA TO COME BACK AND FIND THE RELATION WITH DURATION OR TREATMENT AS WELL AS THE EXTENT OF MORTALITY. SO, FOR ALL THOSE REASONS WE DECIDED TO LAUNCH THE STUDY THAT HAS TWO PHASES, THE FIRST PHASE IS TO STUDY HOW TO BEST RETAIN PATIENT IN TREATMENT. WE WILL ACCEPT THE PATIENT FROM A WIDE TREATMENT SETTING, PRIMARY CARE, SPECIALTY CARE, MENTAL HEALTH OR EVEN CRIMINAL JUSTICE SYSTEM, PATIENT WHO ARE SEEKING TREATMENT, AND ONCE THEY CAME INTO THE TREATMENT STUDY WE WILL NOT RANDOMIZE THEM INTO EITHER SELECTING PARTIAL TREATMENT OR ANTAGONIST TREATMENT BECAUSE OUR EXPERIENCE IN DATA SUGGESTS PATIENT HAS STRONG PREFERENCE FOR EITHER ONE. RANDOMIZATION MAY NOT BE THE BEST WAY TO RETAIN PATIENT. ON THE BUPE ARM, THE PARTIAL AGONIST ARM, WE WANT TO STUDY THE STRATEGY OF MODIFYING CHANGE IN INCREASED DOSE AS A WAY TO IMPROVE RETENTION AND REDUCE NON-RESPONDING PATIENT TO THE TREATMENT. AND ALSO WE USE THIS OPPORTUNITY TO STUDY THE NEW SUSTAINED RELEASE FORMULATION WHICH WE BELIEVE ALSO RELEASE BUPRENORPHINE, IMPROVE COMPLIANCE AND REDUCE DROPOUT. IN THIS PARTICULAR STUDY DESIGN IS A THREE BY TWO FACTORIAL, WE WANT TO REALLY STUDY BY ENHANCING THE PSYCHOSOCIAL SUPPORT PLATFORM BY USING A VERY AGGRESSIVE ASSERTIVE CASE MANAGEMENT TO SPECIFICALLY ADDRESS EACH PATIENT DROPOUT REASONS OR RETENTION DIFFICULTIES, AND MANAGE ALL THOSE AREAS. WE ROAD TEST THE SAME BEHAVIOR SUPPORT SYSTEM FOR PATIENT CHOOSE TO BE RETAINED BY ANTAGONIST, AND THE TREATMENT IS PLANNED FOR TWO YEARS, AND OUTCOME MEASURE IS SIX MONTHS RETAIN IN TREATMENT AS A SUCCESS. FOLLOW-UP WILL BE FOR ONE YEAR. FOR THE SECOND PHASE IS THE DISCONTINUATION PHASE, IN THIS CASE WE WANT TO BE ABLE TO ENROLL PATIENTS THAT CAME OUT OF THE RETENTION STUDY THAT THEY ARE ABLE TO DEMONSTRATE GOOD RETENTION RATE AND IMPROVE THE SOCIAL FUNCTION AND IMPROVED QUALITY OF LIFE. FOR THOSE PATIENTS WE WILL RECEIVE THEM INTO THE STUDY AND, AGAIN, RANDOMIZE THEM INTO TWO BY TWO FACTORIAL STUDY THE STRATEGY FOR TAPERING, EITHER BY DIRECTLY TAPERING FROM THE PARTIAL AGONIST OR TRANSITION PATIENTS FROM PARTIAL AGONIST INTO ANTAGONIST USING THAT AS A DIFFERENT TACTIC HERE TO SEE WHETHER THAT WOULD EASE THE DISCONTINUATION. AND WE ALSO HAVE TESTING TWO DIFFERENT PLATFORMS FOR BEHAVIOR INTERVENTION THAT WILL STRONGLY DISCOURAGE RELAPSE AND FOLLOW A PATIENT CLOSELY, AND RESCUE PATIENTS IF THEY SHOW THEY ARE AT VERGE OF RELAPSING OR DROPPING OUT, REENGAGE THEM BECAUSE THE RISK OF DROPPING OUT AT THIS STAGE WHEN THEY DISCONTINUE THE MOUD HAS VERY HIGH RISK OF RELAPSE AND CONSEQUENCE IS DIRE. ANOTHER PATIENT POOL IS COMING FROM RETENTION STUDY FOR THOSE PATIENTS WHO CHOOSE TO UNDERGO TREATMENT WITH ANTAGONIST. WE WILL DO THE SAME KIND OF STRATEGY TESTING THE BEHAVIOR PLATFORM. SO, THE STUDY IS PLANNED FOR ONE YEAR, AND SIX MONTHS WITHOUT RELAPSE AS A SUCCESS. BUT IF YOU LISTEN TO THIS PARTICULAR FLOWCHART YOU MAY WORRY THAT WE HAVE TO WAIT UNTIL TWO YEARS THAT PATIENT COME OUT FROM THE RETENTION STUDY SO WE ALSO PLAN TO RECRUIT PATIENT AT SAME TREATMENT SITE THAT PARTICULARLY IN THE STUDY, THEY ARE ALSO DOING WELL, WITHOUT PARTICIPATING IN OUR STUDY. THERE ARE PATIENTS WHO ARE DOING WELL, FOR FEAR CRITERIA OF WHAT WE SAID DOING WELL STABILIZE AND THEN ALSO RECRUIT THEM INTO THE STUDY AND THAT CAN BE ONGOING IN PARALLEL, SO THAT IS THE THOUGHT OF THE PLAN RETENTION, DISCONTINUATION, TWO PHASES, RANDOMIZED CONTROL TRIALS. THANK YOU. >> THANK YOU FOR WALKING US THROUGH A VERY CHALLENGING KIND OF DESIGN TO TRY TO TAKE ACCOUNT OF THE REALITIES THAT YOU'VE NICELY OUTLINED. OBVIOUSLY THAT MEANS THAT SOME ASPECT OF THE RANDOMIZATION COULD NOT BE DONE IN THE SQUEAKY CLEAN FASHION THAT YOU MIGHT OTHERWISE TRY TO ACHIEVE BUT YOU'RE TRYING TO COMPENSATE FOR THAT BY CONTINUING TO KEEP RANDOMIZATION IN SOME PARTS OF THIS. SO THIS IS OPEN FOR COMMENTS, DISCUSSION, THIS IS OBVIOUSLY A REALLY IMPORTANT QUESTION WITH A CREATIVE APPROACH. RICK? >> DO YOU WANT COMMENTS ABOUT THE TRIAL DESIGN ISSUES? >> SURE. ANYTHING ELSE. >> I WAS TRYING TO FOLLOW THROUGH. IT'S CREATIVE TO KIND OF THREAD THE NEEDLE OF ETHICS AND PREFERENCE. YOU MAY WANT TO DO STRATIFICATION ON THE FIRST PART THOUGH BECAUSE THE MIX OF HOW THEY COME IN FROM THE RIGHT AND LEFT UPPER SIDES WOULD HAVE SOME IMPLICATION ON DISTRIBUTION IN THE RANDOMIZATION, AND MAY BE SIMPLY STRATIFYING PATIENTS THERE. >> THIS IS JUST A CONCEPT. IT'S IN THE PROCESS OF DEVELOPING PROTOCOL. ALL THESE POINTS I WILL BRING BACK TO OUR INVESTIGATORS. THANK YOU VERY MUCH. >> OTHER COMMENTS? >> I WAS JUST WONDERING, I MIGHT HAVE MISSED IT, THE OUTCOME WOULD BE RELAPSE ONTO OPIOIDS? IS THAT THE OUTCOME MEASURE? >> FOR THIS -- FOR THE DISCONTINUATION PHASE, YES. >> IS THERE EVIDENCE OF SOMETHING THAT WOULD PREDICT THAT AHEAD OF TIME, SO, YOU KNOW, AS YOU COME OFF THE MEDICINE IS THERE SOMETHING YOU CAN SCREEN FOR THAT WOULD BE PREDICTIVE OF, YOU KNOW, GOING BACK ON TO THE OPIOIDS? JUST BECAUSE THE RISK OF THE OUTCOME MEASURE IS SO HIGH. >> TOTALLY. I DIDN'T WANT TO FURTHER COMPLICATE IT FLOWCHART. I THINK THERE'S A LOT OF CHATTERING ABOUT DEVELOPING A PARALLEL BIOMARKER PHENOTYPING KIND OF STUDY TO IDENTIFY SOME OF THE RISK FACTORS, ESPECIALLY FROM THE RETENTION STUDY PART. BECAUSE THESE PATIENTS, YOU KNOW, HAVE TO GO THROUGH THE RETENTION. SO THE DEFINITION OF VERY WELL RETAINED PATIENT WAS STABILIZED CONDITION AND GOOD SOCIAL FUNCTION, ALL THAT REALLY NEEDS TO BE IDENTIFIED, AND DEFINED I DON'T KNOW IF I ANSWERED YOUR QUESTION. >> YEAH, I GUESS I WAS HOPING THERE WAS A CRAVING SCALE WHEN YOU TAKE THEM OFF, THAT WOULD PREDICT THEY ARE GOING TO RUN INTO TROUBLE. THE ADVANTAGE, YOU HAVE SOMEBODY STABLE, THEN YOU MAKE A CHANGE SO PROBABLY THERE ARE TWO OR THREE THINGS THAT HAPPENED BEFORE THEY GO ON TO OPIOIDS AGAIN, AND BECAUSE THE RISK OF DEATH IS SIGNIFICANT WHEN THEY -- YOU KNOW, I'D LIKE TO HAVE SOMETHING. >> YES. AND ONE OF THE THINGS, WALTER, THIS IS ONE OF THE BIG CHALLENGES THAT WE HAVE, HOW DO YOU PREDICT WHEN SOMEONE IS GOING TO RELAPSE, WE OVERRELY ON CRAVING BUT THAT'S CONSCIOUS, YOU DECIDE A DRUG, IN MANY INSTANCES IF YOU'RE CRAVING VERY MUCH, IT WILL INCREASE YOUR RISK BUT SOME PATIENTS WILL TELL, I WILL NOT CRAVE. THE STUDY IS VALUABLE. BY DOING PHENOTYPIC CHARACTERIZATION YOU CAN DETERMINE PARAMETERS THAT MAY LEAD TO RISK. AND WE KNOW FROM PATIENTS ENGAGEMENT ONE OF THE FACTORS THEY CLAIM, TWO FACTORS CONTRIBUTE APART FROM CRAVING TO RELAPSE, THAT THEY FEEL DEPRESSED, AND THE SECOND ONE IS THEY CAN NOT FALL AASLEEP. THERE'S A PROFOUND DISRUPTION OF SLEEP PATTERN. THIS IS PATIENT PERSPECTIVE. I THINK THIS IS ANOTHER OPPORTUNITY TO ENGAGE THE PATIENTS THEMSELVES IN THE STUDY. >> EXACTLY. SO WE WANT TO IDENTIFY FOR PATIENTS WHO ARE THEY AND ASSERTIVE CLINICAL MANAGEMENT, CASE MANAGEMENT, BASICALLY WANT TO ADDRESS THAT VERY SPECIFICALLY, WHY CAN'T YOU STAY OR WHY DID YOU -- WHY ARE YOU GOING TO REUSE? MANY PEOPLE HAVE MANY DIFFERENT REASONS THAT NEED TO BE ADDRESSED VERY SPECIFICALLY. >> CAN I ASK YOU ABOUT THE DISCONTINUATION PHASE, THE NEXT SLIDE. I APPRECIATE YOUR SAYING WE DON'T HAVE TO WAIT TWO YEARS TO BEGIN TO TEST THIS PART OUT BECAUSE THERE ARE PEOPLE WHO HAVE ALREADY BEEN ON TREATMENT, EVEN THOUGH THEY WEREN'T PART OF YOUR RETENTION PHASE. BUT WHAT'S THE NUMBER OF INDIVIDUALS THAT YOU MIGHT EXPECT TO BE ABLE TO ENROLL WHO HAVE AD AD ACHIEVED THAT MILESTONE, WILL WE KNOW SOMETHING WITHIN A YEAR ABOUT THE APPROPRIATE APPROACH TO DISCONTINUATION? WILL WE NOT HAVE ENOUGH POWER? >> YES, SO PROCESS IS SUCH, AFTER WE DEVELOP THE PROTOCOL, THE NEXT STEP IS REALLY LOOKING INTO THE PARTICIPATING SITES. WE CANNOT HAVE A STUDY SO EXOTIC THAT NO PLACE CAN DO THE STUDY. ONCE WE STARTED LOOKING INTO THE SITE, WHETHER IT'S PRIMARY CARE NETWORK, OR IT'S A SPECIALTY CARE NETWORK, GOING THERE, IT'S AN OPPORTUNITY TO STUDY THEIR PROFILE. THEY HAVE TO COME IN TO BE QUALIFIED. AT THAT POINT WE WILL SIT DOWN AND NEGOTIATE WITH EACH OF THEM. AND THIS IS AMBITIOUS STUDY THAT WE ARE PLANNING ON GOING TO 20 TO 25 DIFFERENT SITES, THAT IS HARD WORK. WE WILL HAVE TO LOOK INTO THAT. AND THIS IS THE SAME THING, AS WHEN WE'RE TALKING ABOUT DISCONTINUATION. THERE ARE PATIENTS ON THEIR OWN DISCONTINUE SUCCESSFULLY, THE PATIENTS ARE DIFFERENT. AND THERE ARE PATIENTS WHO STAY ON TREATMENT FOR A NUMBER OF YEARS, AND DOING WELL. AND THEY WANTED TO STAY ON. SO WE HAVE TO LOOK INTO THAT. IT IS CHALLENGING. THANK YOU, YES. >> DO YOU THINK IT'S POSSIBLE TO, AS OPPOSED TO CHECKING TO SEE IF THEY GO AND USE HEROIN, TO MAKE A SAFER OPIOID AVAILABLE SO IF THEY ARE GOING TO CHOOSE TO ABUSE OPIOIDS THAT THERE'S SOMETHING SAFER THAN HEROIN, IS THAT POSSIBLE TO DO AS A STUDY? >> WELL, THAT BECOMES VERY DIFFICULT. CERTAINLY WE DO HAVE METHADONE, DO HAVE BUPRENORPHINE. BUT WE DON'T HAVE LIKE HEROIN, LIKE THEY DO IN EUROPE, SO NO. I DON'T THINK THAT IS PRACTICALLY REALISTIC IN THE CURRENT SITUATION, BUT WE DO HAVE MEDICATIONS THAT CAN DEAL WITH THE CRAVINGS, AND SO THAT'S WHAT WE'RE GOING TO BE ENGAGING, TO GIVE THEM ANOTHER OPIOID THAT IS AIM, RATHER THAN CURRENT MEDICATIONS, ACTUALLY TO -- >> (INAUDIBLE) OUTCOME MEASURES AS OPPOSED TO HEROIN. >> THE ISSUE IS WHAT YOU END UP TAKING IS GOING TO BE VERY MUCH DEPENDENT ON WHAT IS IN YOUR ENVIRONMENT. SO IF YOU'RE IN A SETUP WHERE HAVE YOU ACCESS TO SOME OPIOID DRUGS THAT MAY BE LESS POTENT THAN FENTANYL, YOU MAY BE SAFER THAN IN YOU'RE IN AN ENVIRONMENT WHERE EVERYTHING ALMOST IS LACED WITH FENTANYL, THAT'S OUT OF OUR CONTROL. >> (INAUDIBLE). >> WE WILL BE -- WE ARE EVALUATES, STATES ARE EVALUATING BECAUSE IT'S IMPORTANT TO KNOW WHAT IS THE NATURE OF THE DRUGS THAT PEOPLE ARE DYING FROM. SO THIS IS BEING -- AND THE HEALING COMMUNITIES WILL BE DOING THESE AT GREATER DEPTH THAN MANY OF THE STATES ARE CURRENTLY DOING. >> ONE MORE COMMENT ABOUT THE -- ONE OF THE PROBLEMS WITH THE KNOWN BAD OUTCOME FROM STANDARD FOLLOW-UP, THE FACT IT'S NOT BLINDED, THERE'S A BIG OPPORTUNITY FOR PLACEBO EFFECT OR HAWTHORNE EFFECT, AFFECTING PATIENTS WHO MAY KNOW THEY GOT STANDARD FOLLOW-UP AND THAT'S NOT -- THAT'S KNOWN TO HAVE A BAD OUTCOME. ONE CONSIDERATION MIGHT BE CLUSTER RANDOMIZATION, IF YOU HAVE ENOUGH SITES, TO DO THAT. THEREFORE THERE IS NO KIND OF INTERSITE ISSUE, GOOD AND BAD, ESPECIALLY OPEN RANDOM SITE. >> THANKS, RICK. HEATHER? >> HOW ARE PATIENTS GETTING MEDICATIONS, PAYING FOR THEM OR ARE THEY PROVIDED BY THE STUDY? I COULD SEE THAT MAKING A DIFFERENCE. >> I THINK OUR CURRENT PLAN IS TO PROVIDE BY STUDY. >> OTHER QUESTIONS? >> THANK YOU. THANK YOU VERY MUCH. >> I THINK WE MIGHT HAVE ARRIVED AT THE POINT WHERE CRAVING FOR LUNCH IS BEGINNING TO KICK IN. IT IS NOON. REBECCA, WHAT'S THE LUNCH PLAN? >> FOLKS SHOULD HAVE PRE-ORDERED LUNCHES, AND I'M NOT QUITE SURE IF THE BOXES ARE HERE YET BECAUSE WE'RE A LITTLE BIT AHEAD OF SCHEDULE, BUT CERTAINLY THEY WILL BE DELIVERED AND AVAILABLE. AND SHOULD WE STICK TO OUR PLANNED TIME TO RECONVENE, 1:10? >> SINCE WE'RE STARTING LUNCH EARLY, WE COULD CONVENE EARLIER. COULD WE AIM FOR 1:00? >> 1:00 P.M. >> OKAY. >> WE'LL HEAR ABOUT BRIM. THANK YOU ALL. IT'S BEEN GREAT START TO THIS DAY >> NOW WE'LL PLUNGE IN WITHOUT A BREAK PLANNED FOR THE AFTERNOON, ALTHOUGH WE MIGHT HAVE TO INDUCE SOMETHING IN THERE. WE'LL SEE HOW WE DO. GOING NOW TO THE SECOND OF THE FIVE SPECIFIC PROPOSALS, THIS ONE TO BE PRESENTED BY DR. DAVID SHURTLEFF, TALKING ABOUT BEHAVIORAL RESEARCH TO IMPROVE HEAD INDICATION-BASE TREATMENT FOR OPIOID USE DISORDER, BRIM. >> AS SOON AS I GET THE SLIDES READY, WE'RE GETTING THERE. YEAH, HALF THE EFFORT WAS DEVELOPING THE ACRONYM, BRIM, WE'RE HAPPY WITH IT. CONTINUING THE DISCUSSION WE'VE HAD, HOW TO IMPROVE TREATMENT OUTCOMES FOR OPIATE USE DISORDER, THE FIRST SLIDE WE DISCUSSED THIS MORNING, SUGGESTING ACCESS TO RETENTION MEDICATION-BASED TREATMENT IS PROTECTIVE AGAINST MORTALITY. WHY WE NEED TO GET MORE PEOPLE INTO TREATMENT. TREATMENT SAVES LIVES, IN REALITY HERE. ADHERENCE AS WE TALKED ABOUT IS A MAJOR CHALLENGE. AND AS BETTY BROUGHT UP, AND OTHERS, THERE'S EXTENSIVE DROPOUT IN THE FIRST SIX MONTHS, 60% OF PEOPLE WHO ENTER TREATMENT DROP OUT. OF COURSE WE IT'S IMPORTANT TO KEEP PEOPLE IN TREATMENT, MAYBE FOREVER, STABILIZED TO PREVENT RELOS RE-- RELAPSE. IT'S AN INCENTIVE-BASED PROGRAM, MANY TREATMENT FINDERS PROVIDE DISTASTEFUL IS ONE WAY TO SAY IT, THERE NEED TO BE OTHER APPROACHES TO ENGAGE INDIVIDUALS IN LONG-TERM BEHAVIOR CHANGE, WHERE WE THINK ABOUT NOT ONLY FOR RELAPSE PREVENTION, BUT FOR COMORBIDITY. WE KNOW 40 TO 80% OF INDIVIDUALS IN MOUD EXPERIENCE CHRONIC PAIN, AND AFTER THEY RECEIVE INADEQUATE EVIDENCE-BASED CARE FOR CHRONIC PAIN, THERE'S CROSS-TOLERANCE WITH MEDICATION TO TREAT PAIN -- TREAT OPIATE USE DISORDER WITH THOSE TREATING FOR PAIN. OF COURSE BY VIRTUE OF BEING ON AN OPIOID YOU HAVE INCREASED HYPERALGESIA AND SENSITIVITY TO PAIN. INDIVIDUALS ARE COMORBID FOR MANY CONDITIONS, WHETHER DEPRESSION, SLEEP DISORDERS AND OTHER CONDITIONS. TO TREAT THIS APPROACH WITH ANAY- INTEGRATIVE APPROACH, TO ADDRESS UNDERLYING COMORBID CONDITIONS INCLUDING CHRONIC PAIN, MOOD DISORDERS, ANXIETY, SLEEP, FUNCTIONAL DIFFICULTIES. FROM THE SMOKING CESSATION LITERATURE WE KNOW BOTH TOGETHER ARE BETTER THAN EITHER ALONE. COMBINATION OF PHARMACOTHERAPY WITH MEDICATION IS THE ANSWER TO THIS PROBLEM. SO, AN EXAMPLE HOW WE THINK AT LEAST ONE APPROACH, MINDFULNESS BASE THE INTERVENTION FOR SUBSTANCE ABUSE AND PAIN MANAGEMENT CAN ADDRESS A LOT OF ISSUES PATIENTS ARE FACING WHEN THEY HAVE USE DISORDER AND CHRONIC PAIN. INTERVENTIONS PROMOTE COGNITIVE CONTROL, ENHANCE AWARENESS, CRITICALLY IMPORTANT, NORA BROUGHT UP THE POINT THAT PEOPLE DON'T OFTEN REPORT CRAVING, PART OF THAT IS THEY HAVE LOST THEIR ABILITY TO MONITOR THEIR OWN SELF AWARENESS, THEIR OWN BODILY FUNCTION. CERTAINLY MINDFULNESS BASED INTERVENTION CAN HELP. THEY RESTRUCTURE REWARD, FACILITATE EXTINCTION TO DRUG USE, WITH MINDFULNESS YOU'RE FACED WITHOUT THE NECESSARY EMOTIONAL STATE THAT LEADS TO DRUG INTAKE. THEY CAN REDUCE PAIN CATASTROPHIZING, CRITICALLY IMPORTANT, INCREASE PSYCHOLOGICAL FLEXIBILITY, WHICH WE KNOW IS IMPORTANT FOR DAILY LIFE AND JUST GENERAL WELL-BEING. AND ENHANCE TOP-DOWN MODULATION NOCICEPTIVE INPUT, REFRAMING, NO LONGER AS EMOTIONAL AND STRESSFUL AS WITHOUT THESE INTERVENTIONS. TO PUT A NEURAL BASIS ON THIS, MINDFULNESS-BASED INTERVENTION ENGAGE A VARIETY OF NEURAL NETWORKS AND RANGE OF COGNITIVE PROCESS SUCH AS ATTENTION AND EMOTIONAL CONTROL, AN EXAMPLE WHEN A PATIENT -- WHEN A PERSON IS FOCUSING, FOCUSED ATTENTION, ENGAGING A SERIES OF NETWORKS INCLUDING THALAMUS, PREFRONTAL CORTEX AND PARIETAL CORTEX IN THE FIRST IMAGE AT THE TOP. THAT'S SUSTAINING ATTENTION AND KEEPING THEM ALERT, AND AWARE OF THEIR BODILY FUNCTION. THE EXECUTIVE NETWORK IN YELLOW IS ENGAGING THE BASAL GANGLIA, ANTERIOR CINGULATE CORTEX, IMPORTANT FOR DECISION MAKING, PRE-FRONT CORTEX AND LATERAL VENTRAL CORTEX WE KNOW IN THE PROCESS OF MEDICATION, PROCESS OF LETTING GO AND OPEN MONITORING OF THESE EVENTS, SO YOU DON'T REACT TO THEM BUT YOU'RE AWARE OF THEM. THESE ARE CRITICAL THINKS THINKING ABOUT CHRONIC PAIN AND OPIATE USE DISORDER. WE THINK THEY ARE SO CRITICALLY IMPORTANT, IT'S PART OF THE TREATMENT FOR OPIATE USE DISORDER. SO, THE PURPOSE OF THE BRIM PROGRAM IS TO BRING IN AND INTEGRATE BEHAVIOR AND SOCIAL INTERVENTIONS INTO MEDICATION-BASED TREATMENT FOR OPIATE USE DISORDER TO INCREASE ADHERENCE TO MOUD, ALSO TO PREVENT RELAPSE AND DEAL WITH SOME OTHER ISSUES, IMPROVE ABSTINENCE IN TREATMENT. IN ADDITION WE LAUNCHED THIS IN FISCAL YEAR 18, FORTUNATE THAT GETTING SUBSTANTIAL AMOUNTS OF FUNDS FOR OPIATE CRISIS AND LAUNCHED STATE TARGETED RESPONSE AND THE TWO ARE A PHASE WE PUT OUT, 1801 AND 1802, TO WORK WITH STATES, WITH THE PUBLIC HEALTH SYSTEM, TO OVERLAY THIS BEHAVIORAL INTEGRATIVE APPROACH WITH ONGOING EXISTING EXPANSION OF THE PROGRAM, WE THOUGHT AN IMPORTANT THING TO DO AT THE TIME AND TIMING WAS JUST PERFECT. THE OTHER THING BRIM WE WANTED TO DO, I TALKED ABOUT THIS IN THE PREVIOUS SLIDES, WE WANT THESE BEHAVIORAL INTERVENTIONS TO DEAL WITH COMORBID CONDITIONS, PAIN, DEPRESSION, SLEEP DISTURBANCE AND A TRIGGER FOR OPIATE RESPONSE AND TO BE INTEGRATIVE, ENGAGING FAMILIES, CAREGIVER PROVIDERS AND OTHERS HOW TO APPROACH THIS PROBLEM. WE WERE FORTUNATE IN THE FIRST TWO WAYS TO GET SIX APPLICATIONS FOR FUNDING. YOU CAN SEE FROM THE TITLES THEY REALLY ADDRESS ISSUES AROUND MIND-BODY INTERVENTION FROM BEHAVIOR, BODY AWARENESS, CYNTHIA PRICE IS DOING TO ENHANCE THAT INTROCECPTIVE, PSYCHOSOCIAL PAIN, ACCEPTANCE AND COMMITMENT THERAPY AND COGNITIVE BEHAVIORAL THERAPY. WE HAVE MINDFULNESS ORIENTED RECOVERY ENHANCEMENT WHICH DR. GARLAND HAS DEVELOPED THAT'S BEING TESTED IN A MORE BROAD PERSPECTIVE. MINDFULNESS TRAINING, MINDFULNESS FOR MINDS, YOGA-BASED MINDFULNESS RELAPSE SUPPRESSION IN PREGNANT WOMEN WHICH WE THINK IS REALLY IMPORTANT A VULNERABLE POPULATION THAT NEEDS OUR ATTENTION. CBT CONTINGENCY MANAGEMENT IS THE LAST BY DR. NUNES HERE INVOLVED IN THAT PROJECT. GIVEN SUCCESS OF FY 18 INITIATIVE DECIDED TO CONTINUE THIS, FIGURED THAT SIX APPLICATIONS WAS A GOOD START BUT WE COULD DO MORE IN THIS SPACE. WE WANT TO START 1906, THE SAME INITIATIVE THAT WE LAUNCHED IN FY 18, A FIVE-YEAR AWARD USING THIS TRANSITION AWARD, R61 FOR PLANNING AND MILESTONE-DRIVEN PLANNING FOR ONE TO TWO YEARS AND THEN IMPLEMENTATION PHASE UP TO FOUR YEARS AND ENGAGE MANY MORE INSTITUTES AND CENTERS AND OFFICES ACROSS THE NIH. THIS INITIATIVE HAS CLOSED. WE RECEIVED A ROBUST RESPONSE TO THIS INITIATIVE WHICH WE'RE HAPPY ABOUT. WE ANTICIPATE FUNDING SIX TO EIGHT AWARDS. I THINK YOU'LL BE SEEING THE OUTCOME OF THOSE REVIEW IN THEIR AUGUST -- YOUR AUGUST MEETING HERE SO YOU'LL HAVE A CHANCE TO ACTUALLY WEIGH IN ON WHAT YOU WOULD THINK ARE THE MOST CRITICAL APPLICATIONS TO MOVE FORWARD WITH. IN ADDITION, WE LAUNCHED A LIMITED COMPETITION, THOSE SIX STUDIES I SHOWED YOU PREVIOUSLY ALONG WITH FOUR STUDIES THAT NIDA FUNDED UNDER A SEPARATE RFA WOULD BE ELIGIBLE FOR EXPANSION OF THOSE STUDIES, A WAY TO INCREASE POWER TO LOOK AT EFFICACY IN A MORE ROBUST WAY, INCREASE RECRUITMENT OF UNDERREPRESENTED POPULATION, TO DO THINGS THEY COULDN'T DO A SMALLER BUDGET, GIVING THEM A CHANCE TO EXPAND, APPLICATIONS DUE MARCH 15, WE'RE WAITING TO SEE WHAT THE RESPONSE WILL BE. THAT'S ALL. I'LL TAKE ANY QUESTIONS YOU MIGHT HAVE. >> THANKS, DAVID, FOR A QUICK AND CONCISE SUMMARY BUT I'M SURE THE GROUP HAS COMMENTS. WELL, I THINK THEY DO. YES? CAN YOU TURN ON THE MICROPHONE. >> OKAY. I HAD SOME COMMENTS. I THINK DAVID KNOWS THIS IS NOT DIRECTED NECESSARILY AT THIS PARTICULAR PRESENTATION BUT TO GET A COUPLE OF ISSUES ON THE TABLE THAT I WOULD KIND OF LIKE TO BE THINKING ABOUT AS WE'RE HEARING ABOUT THESE DIFFERENT INITIATIVES. >> SURE. >> AND, YOU KNOW, REALLY THERE'S TWO ISSUES I WANTED TO TALK ABOUT. ONE HAS TO DO WITH WHETHER WE'RE DOING ENOUGH TO ACCELERATE THE SCIENCE, AND THE SECOND ONE ON THE OTHER HAND IS MORE ABOUT ARE WE MAKING RIGHT STRATEGIC INVESTMENTS NOW THAT WOULD ADDRESS SOME OF OUR SORT OF INEVITABLY LONGER-TERM GOALS WITH THIS LARGE NUMBER OF PROGRAMS, AND SO WITH RESPECT TO THE FIRST OF THOSE, I'M KIND OF CURIOUS, HOW WE ARE LEVERAGING IN SOME RESPECTS THE URGENCY OF THIS INITIATIVE TO MOVE TOWARD SORT OF MORE AGGRESSIVE DATA SHARING, AND OPEN SCIENCE PRACTICES IN THE SCIENCE. OBVIOUSLY IF EVER THERE WAS A PROBLEM THAT HAS URGENCY WE SHOULD BE MOVING AS QUICKLY AS POSSIBLE TO MAKE THE DATA THAT ARE BEING COLLECTED AVAILABLE TO THE WIDER WORKFORCE, SCIENTIFIC WORKFORCE SO WE CAN MAKE MORE RAPID PROGRESS, I MEAN, THIS IS THE INITIATIVE I THINK CALLS OUT FOR THAT. AND OF COURSE THE OTHER -- THE REAL ADVANTAGE FOR ACCELERATING THE SCIENCE FOR RAPID DATA SHARING AND AGGREGATION IS BEING ABLE TO AGGREGATE DATA ACROSS THE POSSIBLY -- AGGREGATE ACROSS THE INITIATIVES SO THE RESULTS YIELDED FROM THESE INITIATIVES IS MORE DEFINITIVE RESULTS. SO I THINK WE'RE BOTH -- BOTH OF THOSE WAYS OF MOVING TOWARD STRONGER DATA SHARING AND OPEN SCIENCE POLICIES WOULD ACCELERATE THE SCIENCE. I'M JUST WONDERING IF THAT IS BEING BUILT INTO ANY OF THE INITIATIVES. I HAVEN'T HEARD YET ANYTHING ABOUT THAT, I THOUGHT I WOULD RAISE IT AND PUT IT ON THE TABLE BECAUSE I THINK IT MIGHT BE SOMETHING I'D LIKE TO HEAR ABOUT WITH RESPECT TO NUMBER OF INITIATIVES. >> I THINK THAT WOULD BE FOR THE NETWORKS COMING, WE'LL HAVE DATA COORDINATING CENTERS, THEY ARE TRYING TO SHARE INFORMATION. I THINK JANE WILL TALK A LOT ABOUT THAT. I IMAGINE JANE AND MAYBE OTHERS. CERTAINLY FOR THIS PROGRAM A LOT OF THE RESEARCH IS LINKED TO STATE HEALTH CARE, TO PUBLIC HEALTH SYSTEMS. SO I THINK IT'S EVEN BETTER THAN DATA SHARING. IF THE RESULTS TURN OUT TO BE POSITIVE, IT'S RELATIVELY EASY FOR THE PUBLIC HEALTH AGENCIES TO ADOPT THESE PROGRAMS BECAUSE IT'S PART OF THEIR ONGOING EXPANSION, SO THAT'S AN ADVANTAGE TO DOING IT THIS WAY WITH SAMHSA ACTUALLY AS PART OF THIS PROGRAM. SUCH AS ADDRESSING THAT PIECE OF GETTING THE TRANSLATION AS QUICKLY AND AS SOON AS POSSIBLE TO THE PATIENTS WHO NEED IT. >> SO FOLLOWING UP, OBVIOUSLY WE HAVE A DIVERSE SET OF INITIATIVES THAT WILL REQUIRE DIFFERENT DATA POLICIES, BUT BUILT ON EACH ONE OF THEM, FOR EXAMPLE, ON THE HEALING COMMUNITIES OR JCOIN, CRIMINAL JUSTICE SETTING OR CLINICAL TRIALS NETWORK, WHICH ARE THE LARGEST LARGE INTEGRATED INITIATIVES, THEY HAVE A DATA CENTER THAT IS -- ONE OF THE FIRST THINGS THEY ARE GOING TO DO IS HARMONIZE THE COLLECTION SO THAT THEY CAN BE INTEGRATED, AND ALSO DEVELOP THE METHODS TO GIVE DIFFERENT ACCESS OF INFORMATION TO DIFFERENT TYPE OF RESEARCHERS. AND THIS IS VERY SENSITIVE IN THE WHOLE ADDICTION FIELD BECAUSE OBVIOUSLY SOME OF THE STATES PENALIZE USE OF DRUGS SO WE HAVE TO COME BACK WITH A PROCEDURE THAT ACTUALLY PROTECTS THE PARTICIPANTS. SO THIS IS EMBEDDED INTO THE THREE LARGE PROJECTS. AND AS YOU KNOW, AS ONE OF THE CHANGING STRATEGIES WE HAVE HAD IN OUR INSTITUTE AND FOLLOWING WHAT OTHERS HAVE DONE WITH -- PERHAPS OPENED BY THE HUMAN GENOME IS DEVELOPMENT OF OPEN ACCESS AS MUCH AS WE CAN, FOR THE ABCD, OR HEALINGBCD, PREDICATED ON OPEN PLATFORM, BUT FOR THE CLINICAL TRIALS AND FOR THE JUSTICE SYSTEM WE'RE GOING TO BE WORKING WITH NOT NECESSARILY AS OPEN A SYSTEM, SOMETHING WE WORK WITH. THE OTHER THING WE WERE TASKED BY FRANCIS TO ACTUALLY THINK OF OPPORTUNITIES WHERE IF WE HAD ACCESS AT OTHER DATASETS THAT ARE CURRENTLY MORE RESTRICTED LIKE CMS, COULD WE EXPAND ON THE TYPE OF THINGS THAT WE DO, AND SO WE'RE TRYING TO ALSO USE THE HEALING COMMUNITIES AS AN OPPORTUNITY TO CREATE AN ENVIRONMENT WHERE THAT BECOMES ACCESSIBLE AND AVAILABLE BECAUSE THE TRUTH IS RIGHT NOW WITH THE URGENCY OF WHAT WE'RE DEALING, NOT TO SHARE THE DATA IS UNETHICAL, IF YOU THINK ABOUT IT. >> I AGREE. I THINK IT'S VERY IMPORTANT. >> I APPRECIATE YOUR RAISING IT. AS NORA SAID THIS IS A TOPIC NIH WANTS TO LEAD ON, NOT FOLLOWING ON, WE ARE WRESTLING WITH WHAT KIND OF REQUIREMENTS SHOULD WE PLACE ON EVERY GRANTEE BEFORE WE GIVE THEM MONEY, ABOUT SHARING DATA. IT'S EASIER FOR SOME DATA TYPES THAN OTHERS, LIKE GENOMICS, WE KNOW WHAT THE ANSWER IS WHEN IT COMES TO CLINICAL DATA. IT GETS MORE COMPLICATED AS NORA JUST SAID BUT THAT'S NOT AN EXCUSE FOR HAVING THE DATA UNAVAILABLE. I PROMISE YOU WE WILL PUSH REALLY HARD ON THIS. GO AHEAD. >> THAT'S GREAT. AND THE OTHER THING THAT I WAS -- THE OTHER ISSUE ABOUT STRATEGIC INVESTMENT, IT OCCURRED TO ME LOOKING AT ADDICTION, PREVENTION OF ADDICTION SIDE, LISTENING TO THE PAIN INITIATIVES AND SO ON I'M WONDERING, YOU KNOW, ARE WE -- IS IT POSSIBLE WE COULD BE COLLECTING CRITICAL DATA ELEMENTS WITHIN THESE DIFFERENT INITIATIVES THAT WOULD FILL GAPS THAT WE HAVE CURRENTLY TO ADDRESS LONGER-TERM QUESTIONS, LIKE, YOU KNOW, PEOPLE TALK A LOT ABOUT THE VARIABILITY THAT'S OBSERVED IN PAIN SENSITIVITY PHENOTYPES, OR PAIN REGULATION PHENOTYPES. BUT WHEN YOU LOOK AT THE LITERATURE, IT'S NOT CLEAR WE HAVE A LOT OF INFORMATION ABOUT THE GENETIC ARCHITECTURE OF THESE PHENOTYPES, AND SO IT'S PROBABLY DIFFICULT TO ACQUIRE ENOUGH DATA OF THIS TYPE AND SO I'M JUST WONDERING IF EVEN ACROSS THE ADDICTION PAIN SPECTRUM OF THIS INITIATIVE IF SOME KEY PHENOTYPE SHOULD BE BEING COLLECTED IN ALL OF THEM OR SOMETHING LIKE THAT, YOU KNOW, SO WE GET CLOSER TO THOSE CRITICAL LEVELS OF, YOU KNOW, DATASET SIZES NEEDED TO ADDRESS GENETIC ARCHITECTURE OF THESE ULTIMATELY PRETTY MUCH PSYCHOLOGICAL CONSTRUCTS. I MEAN THAT'S ONE EXAMPLE BUT SEEMS LIKE THAT'S PROBABLY ONE OF MANY EXAMPLES WHERE THE LONGER-TERM DATA NEEDS COULD BE ADDRESSED IN A WAY OF HARMONIZATION ACROSS THE INITIATIVES. >> GREAT POINT. WALTER? >> GREAT POINT. AND ON THE PAIN SIDE, WE ARE INVESTING IN A DATA CENTER, WHICH IS CENTERED IN THE EPPIC NETWORK, COLLECTING FROM MULTIPLE HEAL PROGRAMS AND INDUSTRY FOLKS WHERE THERE IS A LARGE AMOUNT OF DATA ON HOW PEOPLE RESPOND TO DIFFERENT THERAPIES, IN PAIN TRIALS. SO ONE STRENGTH OF THE HEAL IS TO BUILD UP A BIG ONE PLACE, YOU KNOW, ONE-STOP SHOPPING FOR THAT KIND OF DATA. >> CHRONIC PAIN INITIATIVE, LOOK AT GENETIC MARKERS, PREDICTORS WHO TRANSITIONS FROM ACUTE TO CHRONIC, PART OF THE GOAL IS PROSPECTIVE STUDY TO LOOK AT THAT ISSUE DIRECTLY. >> IN THE BRIM STUDIES, IS THERE A FOCUS ALSO ON RETENTION WITH MINDFULNESS INTERVENTION? >> EXACTLY. >> WE HAVE THE SAME ISSUE IN THOSE INTERVENTIONS AS WE DO WITH MEDICATION, RETENTION. >> YES. ONE OF THE STUDIES I DIDN'T HAVE TIME TO GO INTO LOOKING AT THAT, STARTS WITH A MORE MODEST -- INTERVENTIONS ARE TIME CONSUMING, BROUGHT UP BY SOMEONE IN TERMS OF ENGAGEMENT. THE TYPICALLY 8 TO 12 WEEKS, THE ONE STUDY IS LOOKING AT WAYS OF SORT OF FADING THIS PROCESS IN, WITH A LOWER DOSE TO START, AND THEN SLOWLY RAMP UP THE BEHAVIORAL ENGAGEMENT SO THAT THAT KIND OF ISSUE RAISED, CONNIE, IS EXACTLY THAT. MANY PEOPLE WOULD FIND THE INITIAL INTENT TRAINING WOULD BE RATHER RESISTANT, SO WE HAVE TO THINK ABOUT HOW TO TITRATE AS WE DO WITH HOW BLOOD PRESSURE MEDICATION, WE DON'T START WITH OPTIMAL DOSE, WE BUILD UP TO A POINT WHERE IT'S TOLERABLE BUT YET EFFECTIVE AND I THINK THE SAME KIND OF APPROACH NEEDS TO HAPPEN HERE AS WELL. YOU'RE RIGHT. >> AND ALSO AT THE STAGE OF -- MAYBE THAT'S NOT THE RIGHT WORD, OF OPIOID USES, FOR INSTANCE TAPERING INITIATIVE, THAT THE HEALTH SYSTEMS ARE DOING WITHOUT HAVING A LOT OF PAIN CLINICS AND EVERYTHING IN PLACE, IS A PLACE WHERE WE FOUND THIS TO BE HELPFUL, TO TAPER IN, MAYBE THE PSYCHOSOCIAL THINGS LIKE MINDFULNESS AS THE TAPERING IS GOING. >> YES, I'VE BEEN TALKING TO BETH DARNELL AT STANFORD DEALING WITH THIS TAPERING APPROACH. SHE'S A CLINICAL PSYCHOLOGIST BY TRAINING AND THINKING ABOUT THE BEHAVIORAL INTERVENTIONS AND ALSO WITH TAPERING IT'S ABSOLUTELY SPOT ON. THAT'S IMPORTANT. >> I'M VERY ENCOURAGED TO SEE SOMETHING LIKE BRIM BEING ADVANCED, AND I THINK IT'S GOING TO MAKE A SIGNIFICANT CONTRIBUTION TO HELPING US UNDERSTAND THE BEHAVIORAL TECHNOLOGY THAT WE DEVELOPED THUS FAR, WHO WHAT EXTENT THEY HAVE ALLEVIATE THE ISSUE AND A NEED FOR SECOND GENERATION OF MINDFULNESS-BASED INTERVENTION OR MIND-BODY INTERVENTION, SO WE'RE TALKING ABOUT CBT AND MBSR-ISH TYPE OF THERAPIES THAT WERE DEVELOPED DECADES AGO, AND I KNOW THERE HAVE BEEN SIGNIFICANT ADVANCES IN BEHAVIORAL SCIENCE FROM COGNITIVE AND AFFECTIVE SCIENCE IN INTERVENING DECADES, I WONDER WHAT OTHER INITIATIVES COULD BE BROUGHT FORWARD AT SOME POINT TO FURTHER DEVELOPMENT OF THESE BEHAVIORAL THERAPIES. >> IT'S A MAJOR FOCUS FOR OUR INSTITUTE, OUR CENTER, AS YOU WELL KNOW TO SORT OF REALLY START TO LOOK AT THE ACTIVE INGREDIENT AND THINK OF NEW APPROACHES THAT COULD BE BENEFICIAL FOR TRAINING. IT'S A BEHAVIORAL TRAINING APPROACH, AND ONE OF THE APPROPRIATE INGREDIENTS NECESSARY. AT THE END OF THE DAY WHAT WE'RE TRYING TO GET TO HERE, A LITTLE BIT DIFFERENT WITH BRIM, THAN MAYBE SOME OF THE OTHER INITIATIVES, THE SELF CARE MODEL THAT WE'RE REALLY GIVING THE INDIVIDUAL THE TOOLS TO MANAGE THEIR OWN HEALTH AND THEIR OWN DISORDER IN A WAY THAT YOU CAN'T O 24/7 IN A HEALTHCARE SYSTEM. THE DOCTOR SNOT GOING -- IS NOT GOING TO BE THERE EVERY STEP OF THE WAY. PROVIDING STRATEGIES AND TECHNIQUES ALLOWS THE INDIVIDUAL TO BECOME PROFICIENT IN WAYS TO MANAGE THEIR HEALTH AND BEHAVIOR, AND THAT'S THE GOAL HERE. WE THINK, AGAIN, THIS HAS LONG-TERM IMPLICATIONS FOR NOT ONLY THINKING ABOUT OUD, DEALING WITH MANY STRESSES IN LIFE BEYOND THEIR ADDICTION OF COURSE, AND BY PROVIDING THESE TOOLS AND SELF-CARE APPROACH, THEY CAN ADAPT TO OTHER CONDITIONS IN THEIR LIVES. AND THAT CAN CERTAINLY LEAD TO BETTER HEALTH OUTCOMES GENERALLY. THAT'S THE REAL GOAL HERE. >> THANK YOU. >> DAID, THANK YOU VERY MUCH. THANKS TO THE WORKING GROUP FOR COMMENTS. OKAY. WE'RE NOW GOING TO SHIFT INTO THREE PRESENTATIONS THAT ARE MORE IN THE ZONE OF DEVELOPING NEW ALTERNATIVES FOR MANAGEMENT OF PAIN THAT ARE NOT ADDICTIVE. AND THE FISHES OF THOSE -- FIRST IS PRE-CLINICAL RESEARCH EFFORT. WALTER, YOU AND AMIR ARE LISTED HERE TO PRESENT THAT, SO HOW DO YOU WANT TO GO? >> AMIR, DO YOU WANT TO COME TO THE TABLE? AMIR TAMIZ IS DIRECTOR OF DIVISION OF TRANSLATIONAL RESEARCH AT NINDS. AND I'LL TAKE THAT FIRST. AND SO WE'RE GOING TO TALK ABOUT TWO AREAS THAT HAVE BEEN TEED UP, AND WHICH WE WOULD BE INTERESTED IN INPUT FROM THE GROUP, THE FIRST OF WHICH IS THE EFFORTS TO KIND OF ACCELERATE THE DISCOVERY AND VALIDATION OF TARGETS FOR NEW NOVEL PAIN THERAPIES, SO THIS GOES BACK A WHILE. SOME PEOPLE AROUND THE TABLE WERE HERE NOT LAST SUMMER BUT THE SUMMER BEFORE, THREE MEETINGS, YOU SEE IN THE BOXES THERE, AND THE BOTTOM TWO, DEVELOPMENT OF SAFE EFFECTIVE NON-ADDICTIVE PAIN TREATMENTS, AND LAST ONE UNDERSTANDING NEUROBIOLOGICAL MECHANISMS OF PAIN, KIND OF WAS A FOUNDATION OF OUR THINKING AND DEVELOPING THESE PROJECTS. SO WE CONSULTED WITH EXPERTS ACROSS GOVERNMENT, INDUSTRY AND ACADEMIA IN THOSE MEETINGS, PRIMARILY BASED ON PHARMACOLOGICAL AREAS THAT COULD BEST BE ADDRESSED BY PUBLIC/PRIVATE PARTNERSHIP, BUT WE HAVE KIND OF INCORPORATED THE DEVICE WORLD INTO THIS THINKING AS WELL. AND AS I MENTIONED, THE STRENGTH OF NIH HAS BEEN DISCOVERY OF NEW TARGETS, AND THAT'S BEEN QUITE ROBUST IN THE PAIN FIELD, SOME MEETINGS PEOPLE WOULD SAY WE HAVE ENOUGH TARGETS, PLENTY OF TARGETS. THE ISSUES IS WHICH ARE THE GOOD ONES TO GO AFTER, GETTING US TO VALIDATION STUDIES TO TELL WHICH OF THESE BIOLOGICAL TARGETS THAT PEOPLE FIND IN THE PAIN PATHWAY ARE GOING TO BE POTENTIALLY EFFICACIOUS TO HIT. VALIDATION HAS BEEN AN ISSUE FOR MANY OF THE THERAPY DEVELOPMENT PROJECTS, AND SO WE WILL PUT EMPHASIS INTO VALIDATION FOR THIS PURPOSE SO THAT WHEN A POTENTIAL TARGET COMES OUT WE'LL FUND STUDIES TO GET TO ROBUSTNESS OF TARGET. DO YOU SEE THE SAME EFFECTS WITH MULTIPLE DIFFERENT SITES, IN DIFFERENT STRAINS AND SPECIES, WHEN YOU CHECK DIFFERENT AGES, GENDER OF ANIMALS AND GENERALIZABILITY TO SEE IF THE EFFECT IS SEEN IN ONE OR MULTIPLE PAIN MODELS, HOW GENERALIZED IT IS ACROSS THE KIND OF CONSIDERATIONS THAT YOU WOULD HAVE TO UNDERSTAND BEFORE YOU BROUGHT IT INTO PATIENTS. AND THE HOPE IS WE CAN LOWER THE RISK OF ADOPTING THE TARGET INTO TRANSLATIONAL PROJECTS, WHETHER MOLECULES, NATURAL SUBSTANCES OR DEVICES. AND THERE HAVE BEEN SOME REALLY INTERESTING AREAS, AS I SAID, THAT HAVE DEVELOPED OVER THE LAST 10 YEARS OR SO. CERTAINLY IN THE SMALL MOLECULE FIELD, THERE ARE MULTIPLE TARGETS, CHANNELS, LIPIDS, ENZYMES, RECEPTORS, THERE'S NEW WAYS DESIGNING INTERACTING WITH THESE RECEPTORS, YOU KNOW, STRUCTURAL PROTEIN CHEMISTRY AND IMAGING, IN SILICO DOCKING, AND ALLOW YOU TO IN SILICO SCREEN MILLIONS OF COMPOUNDS FOR ABILITY IT REACT WITH YOUR RECEPTOR OF INTEREST ONCE YOU HAVE THE STRUCTURE. AND BIOLOGICS, THE BIOLOGICS FIELD IS CERTAINLY EXPANDED, EVEN IN THE NERVOUS SYSTEM WITH ANTIBODIES, CELL-BASED THERAPIES, THE BRAIN INITIATIVE IS HEAVILY INVESTED IN DEVELOPING MEANS OF EITHER TURNING ON OR TURNING OFF SPECIFIC CELL TYPES IN THE BRAIN, AND THIS CAN BE DONE INVASIVELY BUT ALSO IF YOU CAN GET THE GENE OF INTEREST INTO THE BRAIN, YOU CAN USE CHEMICALS TO TURN ON AND TURN OFF SPECIFIC NEURON TYPES, VERY PRECISELY. ONE RECENT EXAMPLE THAT, YOU KNOW, IS JUST KIND OF -- PULLS AT YOUR IMAGINATION IS A STUDY BY MARK SCHNITZER AT STANFORD, IDENTIFIED NEURONS IN THE BASAL AMYGDALA, WHEN THEY TURN OFF THE NEURONS THE ANIMALS FEEL PAIN FINE BUT DON'T CARE. THEY HAVE NO KIND OF AFFECTIVE RESPONSE TO THE PAIN. SO TRYING TO DISSECT THE CIRCUITS NOW I THINK IS POSSIBLE LIKE NEVER BEFORE. SO WITH THAT I'M GOING TO TURN IT OVER TO AMIR, WHO IS GOING TO TALK ABOUT THE PRE-CLINICAL SCREENING PLATFORM FOR PAIN. >> THANKS, WALTER. I ONLY HAVE A FEW SLIDES HERE, BUT I'LL VERY QUICKLY -- YOU'LL RECOGNIZE THIS SLIDE. THAT'S GOOD. SO, THE PRE-CLINICAL SCREENING PLATFORM FOR PAIN HAS BEEN INTENSIVELY DEBATED AT THE NATIONAL ACADEMIES FOR TRANSLATIONAL RESEARCH, AND INTERNALLY WITH NINDS AND OTHER INSTITUTES. AND THE GOAL AND STRATEGIES ARE PRETTY WELL DEFINED AT THIS STAGE, SO THE MISSION FOR THE PROGRAM IS TO ACCELERATE DRUG DISCOVERY AT THE PRE-CLINICAL STAGE AND DE-RISK ASSETS SO THEY HAVE A QUICK ACCESS TO ADDITIONAL RESOURCES AND CLINICAL TRIALS. WORKING BACKWARDS ACROSS THE BULLETS HERE, WE WANTED TO GENERATE HIGH QUALITY DATA TO DE-RISK PROJECTS, DEVICES, SMALL MOLECULES, BIOLOGICS, NATURAL PRODUCTS, TO REALLY COME UP WITH NEW THERAPIES THAT CAN ADVANCE TOWARDS CLINICAL TRIALS. THE WAY IS ACQUIRE NEW MODELS FOR PAIN, AND WE'VE REACHED OUT TO THE COMMUNITY. WE'VE HAD TWO SPECIFIC WORKSHOPS, SOME OF YOU HAVE BEEN GRACIOUS ENOUGH TO REALLY PUT A LOT OF INPUT INTO THESE WORKSHOPS, AND GIVEN US GUIDING PRINCIPLES TO FOLLOW. AND TO DO ALL THIS WE WANT TO ESTABLISH THIS PRE-CLINICAL TESTING PARADIGM, AND TO IDENTIFY THE PROTOCOLS THAT ARE INDUSTRY STANDARD THAT ARE WELL KNOWN, THAT ARE WELL ESTABLISHED, AND BRING THEM ALL TOGETHER SO THAT ALL WITHIN THE SAME ROOM, SAME ORGANIZATION, WE CAN ACTUALLY GENERATE REALLY ROBUST DATA. SO, WE HAVE A LOT OF EXPERIENCE, BASED ON A SIMILAR PROGRAM, WE'VE HAD SUCCESSFUL ANTI-CONVULSANTANT SCREENING PROGRAM NOW CALLED ETSB. AS YOU SEE ON THE RIGHT THE PROGRAM WAS ESTABLISHED VERY EARLY ON 1970s BUT IMMEDIATELY AFTER ITS ESTABLISHING HAS CONTRIBUTED TO SEVERAL DRUGS BEING ABLE TO FIND THEIR WAY TOWARDS CLINICAL TRIALS AND TO PATIENTS, MOST RECENTLY EPIDILEX WAS A THERAPY STUDIED WITHIN THIS NETWORK, WE HAVE A LOT OF EXPERIENCE, WE KNOW WHAT THE BEST PRACTICES ARE, WE'RE HOPING TO ADAPT LEARNING TO QUICKLY SET UP EPSD AND GET IT OPERATIONALIZED. THIS WILL BE A CONTRACT MECHANISM, SET UP PRE-CLINICAL TESTING. PART WILL HAVE A PUBLIC DATABASE WHERE WE'LL PUBLISH ALL OUR FINDINGS, OUR PROTOCOLS, A WAY OF HARMONIZING THE THINGS KNOWN IN THE COMMUNITY, PUBLISHES A LOT OF DATA THAT PERHAPS HAS BEEN CONTROVERSIAL BUT ESTABLISHING STANDARDS WE CAN RELY ON. THESE ARE THE GOALS WE SET FORTH. FIVE-YEAR PROGRAM THAT WE THINK WILL HAVE A HUGE CATALYTIC IMPACT, SO FOR LAST YEAR WE SET FORTH TO RECRUIT AN ADVISORY GROUP WHICH WE'VE DONE. WE HAD TWO SPECIFIC WORKSHOPS TO BETTER UNDERSTAND THE PAIN MODELS, AND HOW THEY FIT IN AS PART OF THE PROGRESS TOWARDS CLINICAL TRIALS. AND WE HAVE WORKED WITH THE ETSB GROUP AND THE ADVISORY GROUP TO REALLY BETTER UNDERSTAND WHERE THE WORKING FUNNELS ARE AND ESTABLISH THE ROBUST PROTOCOLS THAT WE NEED TO GET GOING. WE'RE WELL WITHIN OUR ACTIVITIES WE PROMISED TO DO FOR 2019. WE HAVE ALREADY STARTED TESTING THROUGH A SUBCONTRACT TO OUR ETSB GROUP, AND WE'VE STARTED DEVELOPMENT OF NEW MODELS AND SPECIFICALLY REALLY FOCUSING ON ENDPOINTS THAT A LOT OF THESE MODELS HAVE IN COMMON. WE'RE VERY CLOSE TO PUBLISHING A REQUEST FOR PROPOSALS FOR THE LARGER AWARD THAT WE'D LIKE TO HAVE AS PART OF THE NEXT FIVE YEARS. WE PLAN TO BE UP AND RUNNING IN THE NEXT FEW MONTHS, BRINGING NEW MODELS, AT THE SAME TIME SETTING UP REALLY ROBUST PROTOCOLS TO START TESTING COMPOUNDS AND DEVICES AND BIOLOGICS, ALL WITHIN THE SAME PLATFORM, AND WE HOPE TO BE VERY GOAL DRIVEN AND WITHIN A FEW YEARS WE'D LIKE TO LOOK BACK AND TO REALLY MAKE SURE THAT WE HAVE SET FORWARD MEANINGFUL MILESTONES WE WANT SET FORWARD, NOT ONLY SETTING UP BUT MAKING SURE WE ACHIEVE THEM. WE UNDERSTAND THE PROGRAM IMPACT AND ALSO DECIDE WHAT THE NEXT STEPS MAY BE FOR US BEYOND 2023. >> I WANT TO SAY SOMETHING ABOUT HOW THINGS GET INTO THAT PLATFORM. >> SO, WE SHOULD BE UP AND RUNNING VERY SHORTLY. WE'RE HOPING TO ACTUALLY START RECRUITING FOUR NEW COMPOUNDS, BIOLOGICS AND DEVICES THAT COME IN. THIS IS REALLY AN OPEN INVITATION FOR ANYONE TO SUBMIT GOOD IDEAS TO US. THIS IS OPEN NATIONWIDE AND ACTUALLY BEYOND UNITED STATES, FOR ANYBODY THAT HAS GOOD IDEAS ABOUT THERAPIES THAT MAY HAVE A GOOD POTENTIAL TO GO FORWARD. WE HAVE TWO STAGES AT WHICH WE WILL TEST THINGS. ONE, WE WANT TO MAKE SURE THESE ARE NOT ADDICTIVE SO WE HAVE IN VITRO AND IN VIVO MODELS TO ASSESS FOR THEIR SPECIFIC MECHANISM OF ACTION. WE HAVE SET UP BATTERY OF PRE-CLINICAL ANIMAL MODELS TO ESTABLISH EFFICACY FOR THESE COMPOUNDS. BUT IT'S REALLY OPEN FOR THE LARGER COMMUNITY TO COME IN AND FOR US TO TEST MOLECULES. >> GREAT. NOW JONI RUTTER WILL TALK ABOUT THE PROGRAM OUT OF NCATS DEVELOPING DRUGS AND TESTING PLATFORMS FOR PAIN ADDICTION AND OVERDOSE. >> OKAY. THANK YOU. HELLO, I'M JONI RUTTER, DEPUTY DIRECTOR OF THE NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES, ALSO KNOWN AS NCATS. I'M GOING TO GIVE A BRIEF OVERVIEW OF NCATS'S ROLE IN HEAL INITIATIVE ON TESTING PLATFORM FOR PAIN ADDICTION, OVERDOSE, AND THE NCATS COMPONENT FOR THIS SIDE OF THE HOUSE INCLUDES BOTH INTRAMURAL AND EXTRAMURAL COMPONENTS. SOME OF THE PROGRAMS ARE THROUGH THE EXTRAMURAL ONLY SIDE WHICH IS SHOWN HERE IN BLUE, SOME ARE THROUGH EXTRAMURAL AND INTRAMURAL COLLABORATIONS WHICH ARE SHOWN IN GREEN, AND SOME ARE JUST THROUGH INTRAMURAL COLLABORATIONS AND THOSE ARE THE ONES IN PURPLE. SO FIVE OF THE SIX INCLUDE INTRAMURAL COLLABORATIONS HERE. I WANT TO FOCUS A LITTLE BIT ON THOSE INTRAMURAL COLLABORATIONS BECAUSE IT'S A LITTLE BIT DIFFERENT THAN WHAT WE'VE HEARD BEFORE. THROUGH THESE PROGRAMS, THERE ARE OPPORTUNITIES TO COLLABORATE WITH THE INTRAMURAL AND NCATS RATHER THAN FUNDING. THESE ARE COLLABORATIONS WITH THE NCATS SCIENTISTS, THEIR RESOURCES AND EXPERTISE IN THE PRE-CLINICAL ASSAY AND THERAPEUTIC DEVELOPMENT SPACE. APPLICANTS CAN TAKE ADVANTAGE TO MOVE FINDINGS FORWARD THROUGH TRANSLATIONAL PATH. NCATS HAS EXPERIENCE TO DEVELOP SYSTEMS APPROACHES THAT IMPROVE EFFICIENCY AND EFFECTIVENESS OF THE TRANSLATIONAL PROCESS. AND SO APPLICANTS CAN THEN ACCESS OUR STATE-OF-THE-ART TECHNOLOGIES, TO MAKE PRE-CLINICAL RESEARCH MORE EFFECTIVE, AND MORE PREDICTIVE AND MORE EFFICIENT, OR DE-RISK POTENTIAL DRUG TARGETS OR RESEARCH PROJECTS TO MAKE THEM MORE ATTRACTIVE FOR COMMERCIAL INVESTMENT. THE WORK DONE WITH THE APPLICANT IN THIS, THROUGH THIS COLLABORATION, THE GOAL IS TO BUILD A COLLABORATION PLAN WITH THE INVESTIGATOR TOGETHER WITH NCATS TEAM, AND THEN THE NCATS TEAM WITH THE P.I. THEN WORKS THROUGH THAT PLAN TO PUSH THE PROJECT FORWARD. SO IT'S A COLLABORATION, NOT NECESSARILY SOMETHING THAT'S FUNDED THROUGH A GRANT CONTRACT OR COOPERATIVE AGREEMENT. SO, THROUGH THIS WORK THERE ARE TWO GENERAL PATHS I WANT TO DRAW YOUR ATTENTION TO. ONE IS ON THE TOP ROW WHERE WE'RE TALKING ABOUT USING HUMAN-BASED PLATFORMS FOR TESTING NEW TREATMENTS OR MODULATING BIOLOGICAL MECHANISMS, DEVELOPING ASSAYS THAT WILL BETTER HELP UNDERSTAND PARTICULAR COMPOUNDS OR THERAPIES BEING EXAMINED, AND SO THESE CELL-BASED ASSAYS CAN RUN FROM VERY SIMPLE ASSAY, THROUGH SINGLE-CELL-BASED ASSIST OR SCREENS TO IMPROVE PREDICTION OF IN VIVO HUMAN EFFECTS OF COMPOUNDS THROUGH HERE iPSC DERIVED NEURONS, FOR EXAMPLE FOR PAIN AND REWARD PATHWAYS. SO FOR EXAMPLE, YOU COULD IMAGINE IT'S POSSIBLE NOW TO TAKE FIBROBLASTS FROM A PATIENT SUFFERING FROM PAIN AND CREATE AN iPS CELL FROM THAT PARTICULAR PATIENT, AND DERIVE PAIN SENSORY NEURONS, NOCICEPTORS, TO STUDY THERAPEUTIC APPROACHES MOST EFFECTIVE FOR THAT PATIENT, BEFORE GIVING THE PATIENT THAT DRUG SO YOU CAN TEST IN IN VIVO SYSTEMS THERE ARE THERE TO BETTER MIMIC THAT ACTIVITY. SO WE'RE TALKING ABOUT SINGLE CELL-BASED DERIVED ASSAYS PLUS 3D OR MORE COMPLEX 3D BIOFABRICATED TISSUE MODELS, OR EVEN MULTI-ORGAN-BASED PLATFORMS TO MODEL MULTI-CELLULAR TISSUES THAT WOULD SORT OF REFLECT THOSE DISEASE STATES FOR DRUG RESPONSES. AND THEN THE OTHER THING ON THE BOTTOM HERE, THE ROW ON THE BOTTOM, IS PUTTING POTENTIAL COMPOUNDS THROUGH THEIR PACES THROUGH THE PRE-CLINICAL REGULATORY REQUIREMENTS. AND SO THIS IS SORT OF ANOTHER GROUP IN WHICH THE NCATS INTRAMURAL PROGRAM CAN REALLY ASSIST. THE GOAL HERE IS TO ACCELERATE TRANSLATION OF NOVEL COMPOUNDS TO ENABLE INDS FOR SUBSEQUENT CLINICAL TESTING FROM THE VERY EARLY PHASES OR STAGES OF PRE-CLINICAL DEVELOPMENT, AND SO FOR DEVELOPMENT OF NEW CHEMICAL STRUCTURES TO MODULATE NOVEL TARGETS, SORT OF BY THE BRUTE FORCE EFFORTS THAT COMBINE ARTIFICIAL INTELLIGENCE, MACHINE LEARNING, WITH SYNTHETIC CHEMISTRY AND BIOLOGIC TESTING TO SCREEN THESE COUNTS OF COMPOUNDS BETTER, FASTER, CHEAPER, IF YOU WILL. OR ALL THE WAY THROUGH DEVELOPMENT OF PHARMACOLOGICAL PROBES, FOR NOVEL TARGETS, WE WOULD EMPLOY HIGH-THROUGHPUT ASSIST, SCREEN LARGE COMPOUND, ARSENAL OF CHEMISTS IN HOUSE, WE HAVE THE LARGEST MEDICINAL CHEMISTRY PROGRAM AT THE NIH, AND THEY CAN HELP TO OPTIMIZE AND VALIDATE THESE PROMISING COMPOUNDS AND DO INITIAL ADME AND TOX TESTING, FOR EXAMPLE. LATER STAGES TO PRE-CLINICAL DEVELOPMENT WHICH IS DEVELOPMENT OF INVESTIGATIONAL DRUGS, FOR READY CLINICAL TESTING, AND, AGAIN, REGARDLESS OF THE CLINICAL MODALITY OR THERAPEUTIC MODALITY OF THE SMALL MOLECULES OR BIOLOGICS OR GENE OR CELL-BASED THERAPIES, FOR EXAMPLE, NCATS IS READY TO PROVIDE A VARIETY OF CAPABILITIES FOR STUDYING, FOR EXAMPLE, PK/PD SOMETIMES OF STUDIES, GLP SAFETY, EVALUATION, FORTY TOXICOLOGY OR GNP SCALING TO DO GNP TO PREPARE, NCATS IS POISED AND READY TO PROVIDE. IN A NUTSHELL, THE PROGRAMS ARE MEANT TO ENABLE INVESTIGATORS WITH THE PROMISING FINDINGS TO THEN TRAVERSE THAT SORT OF VALLEY OF DEATH OF THAT TRANSLATIONAL PIPELINE, WHICH IS THE SPACE THAT NCATS IS MOIST COMFORTABLE IN WORKING. AND WE HAVE CONSIDERABLE EXPERTISE IN THIS SPACE AND CAN BRING THIS TO BEAR FOR THE HEAL PROGRAM. AND I -- JUST TO REHAPPEN HERE, THE NCATS COMPONENTS OF THE HEAL INITIATIVE BOTH ARE TO THE EXTRAMURAL AND INTRAMURAL PROGRAM, BUT I FOCUS HERE MORE ON THE INTRAMURAL SIDE SINCE THEY NOT BE AS FAMILIAR TO YOU BUT I WANT TO POINT OUT THE EXTRAMURAL FUNDING OPPORTUNITIES HERE AT THE BOTTOM LOOKING AT THE BIOFABRICATED 3D TISSUE MODELS AS WELL AS TISSUE CHIPS, AND WE ALSO HAVE A CHALLENGE FOR THE SORT OF DEVELOPING INNOVATIVE AND CATALYTIC APPROACHES TOWARDS SOLVING OPIOID CRISIS. AND THAT'S ONE THAT'S NOW OPEN. THE OTHER TWO RFAs ARE NOW CLOSED. SO I'LL END WITH WHAT -- WHAT MAKES THE INTRAMURAL COLLABORATION'S APPROACH SO APPEALING, DESPITE THE FACT THERE'S NO MONEY CHANGING HANDS FOR THIS SIDE OF THE COIN, IS SINCE IT'S NOT A GRANT, IT'S A COLLABORATION, SO THERE'S ACCESS TO THESE RESOURCES AND EXPERTISE THAT THE SUCCESSFUL APPLICANT DOESN'T HAVE TO PAY FOR. THIS MEANS THAT THE INVESTIGATOR CAN USE THE FUNDING THAT THEY GET FROM THE GRANTS AND CONTRACTS OR OTHER PROGRAMS, WHILE THE NCATS COLLABORATIONS THEN WORK IN PARALLEL. SO THAT'S A REAL ADVANTAGE. THERE ARE BUILT-IN MILESTONES TO HELP FAST AND MAKE SURE ANY PROJECT THAT CONTINUES THROUGH THE COLLABORATION PIPELINE HAS A HIGH LIKELIHOOD OF SUCCESS AND IN A SENSE THE HEAL PROJECTS THAT DO PROGRESS, IT ALLOWS A PROCESS BY WHICH THERE CAN BE ON-RAMPS INTO THIS TRANSLATIONAL PIPELINE, WITH THIS DEEP EXPERTISE AND RESOURCES TO MOVE THOSE PROJECTS FORWARD, AND EVEN PROVIDE THE OFF-RAMPS, THE HAND-SHAKES TO LATER COMMERCIALIZATION STAGES FOR CLINICAL TESTING OR CLINICAL TRIALS OR THOSE COMMERCIALIZATIONS. SO IT'S THE END TO END PROCESS WE'RE TRYING TO ADDRESS FOR THE NCATS INTRAMURAL COMPONENT HERE AND THEIR COLLABORATIONS. I WILL SAY TOO THAT AT THE MAY MEETING IN A FEW MONTHS THERE WILL BE MORE EXTENSIVE DISCUSSIONS ABOUT THE PROJECTS THAT ARE ONGOING THERE, THROUGH THIS PROGRAM. AND YOU'LL HEAR MORE ABOUT IT THEN. SO I'LL LEAVE IT THERE AND MOVE FORWARD. >> TERRIFIC. THANKS, WALTER, AMIR AND JONI. WE'RE OPEN FOR DISCUSSION, QUESTIONS. LET ME START BY ASKING, WALTER, YOU MADE THE POINT EARLY ON THIS IS NOT JUST ABOUT DISCOVERY OF NOVEL TARGETS BUT VALIDATION OF THOSE TARGETS. AND MUCH COMMENTARY ALSO AS PART OF WHAT WAS PRESENTED HERE ABOUT WHAT KIND OF MODELS ARE THERE THAT YOU MIGHT BE ABLE TO DEPEND UPON. HOW GOOD ARE THE MODELS? GIVE US A QUICK RUNDOWN, IF YOU HAD TO TRUST A MODEL TO TELL YOU A PARTICULAR TARGET IS LIKELY TO LEAD TO A SUCCESSFUL PAIN THERAPEUTIC, WHAT MODEL WOULD YOU PICK? THERE MUST BE MANY DIFFERENT ONES THAT MODEL DIFFERENT TYPES OF PAIN BUT WHERE ARE WE? IS THIS A SOLVED PROBLEM? OR IS THIS A POTENTIAL MAJOR POTHOLE? IS IT SOMEWHERE IN BETWEEN? >> I WOULD GUESS WE'RE KIND OF IN BETWEEN OR A MAJOR POTHOLE. WHEN IT COMES TO CHRONIC PAIN, I THINK. ACUTE PAIN I THINK THE MODELS FOR ANALGESIA ARE PROBABLY PRETTY WELL TREAD. THERE IS NO PAIN MEDICINE ON THE MARKET THAT DIDN'T WORK IN ANIMALS, SOMEONE SAID. I THINK YOU CAN SEE HOW THAT HAPPENED. IN CHRONIC PAIN, YOU KNOW, THERE ARE SOME THAT ARE SPECIFIC TO CERTAIN TYPES OF PAIN, SO ONE THAT'S USED MOST COMMONLY, WAS USED IN THAT BRAIN PAPER I MENTIONED, WAS A PARTIAL LIGATION OF SCIATIC NERVE WHICH GIVES A NEUROPATHIC PAIN MODEL. DOES THAT APPLY TO OSTEOARTHRITIS? MAYBE NOT. I THINK FOR SOME OF THESE THINGS WE'LL HAVE TO GO TO, YOU KNOW, A MODEL THAT'S MUCH MORE RELEVANT. I DON'T KNOW IF KEN WANTS TO PIPE IN HERE IN TERMS OF, SAY, OSTEOARTHRITIS MODELS, BACK PAIN MODELS, I DON'T KNOW OF ANY GOOD BACK PAIN MODELS THERE ARE IN ANIMALS. THERE WERE, YOU KNOW, POST-CHEMOTHERAPY MODELS ARE PRETTY GOOD, SIMILAR TO THE POST-NEUROPATHIC PAIN YOU GET FROM CHEMOTHERAPY DRUGS, CAN YOU MODEL THOSE PRETTY WELL IN AN ANIMAL. DIABETIC NEUROPATHY, SIMILARLY. SO I THINK WHAT WE'LL BE DOING IS TRYING TO MATCH UP THE ASSET WITH THE POTENTIAL POPULATION AND THE BEST ANIMAL MODEL, AND THEN TRY TO DEVELOP BETTER ONES AS WE GO ALONG. AND IF WE CAN GET THE DATA FROM INDUSTRY, ON WHAT THEIR DRUG SHOWED IN ANIMAL MODELS AND WHAT HAPPENED IN HUMANS, I THINK THAT KIND OF MASSIVE AMOUNT OF DATA MIGHT POINT TO SOME LESSONS. >> OKAY. >> DO YOU WANT TO BASH ME FOR ANYTHING I SAID? >> LET'S HEAR WHAT KEN LAST TO SAY. >> I THINK YOU'RE RIGHT. IT OPENS MORE QUESTIONS. MOST OF THE TRANSLATION IN THE PAIN SPACE HAS BEEN REVERSE TRANSLATION, TAKE A NON-STEROIDAL AL WHICH WORKS IN HUMANS, AND TEST IT IN ANIMAL MODELS. IF IT WORKS YOU GOT A GOOD ANIMAL MODEL. THAT'S THE TRANSLATION WE'VE GOT. WE'VE NEVER TAKEN ANYTHING THAT WORKED IN ANIMALS THAT'S A NEW MECHANISM OF ACTION OUTSIDE NSAIDs, OPIOIDS, TRICYCLIC ANTI-DEPRESSANTS, PUT IT THROUGH, TRANSLATED IN THE ANIMAL ALL THE WAY THROUGH. THERE'S A COUPLE EXAMPLES BUT NOT MANY >> THE EPILEPSY PLAN WE DID HAVE PAIN MODELS, FOR A LONG TIME, BECAUSE IT WAS PRETTY CLEAR COMPANIES WERE NOT INTERESTED IN MAKING ANOTHER ANTI-CONVULSANT, THEY WANTED TO MAKE ONE THAT WORKED FOR PAIN. SO THE PAIN MODELS IN THE EPILEPSY PROGRAM WENT BACK TEN YEARS. >> DIANA? >> WALTER, TO WHAT EXTENT IS SEX AS A BIOLOGICAL VARIABLE BAKED INTO ALL THESE MODELS? I KNOW THAT THERE ARE NIH-WIDE GUIDANCE, THERE IS NIH-WIDE GUIDANCE, BUT WHAT ABOUT THE CELLULAR LEVEL? ARE THERE GOING TO BE OVERALL EFFORTS LOOKING AT HOW MALE CELLS VERSUS FEMALE CELLS REACT TO PAIN? >> WELL, I HAVEN'T THOUGHT ABOUT THE CELL, AT THE CELL LEVEL. AT THE SYSTEM LEVEL THERE'S TREMENDOUS DIFFERENCE. I JUST AT NOON WENT TO A TALK WHERE THE FINDINGS ON RESILIENCE AND VULNERABILITY WERE COMPLETELY DIFFERENT IN MALES AND FEMALES. SO AS YOU GET TO THE ANIMAL MODELS IN THE CIRCUITS, THAT'S REALLY CRITICAL. >> IN SOME DOWN SYNDROME WORK WE'RE SEEING DIFFERENCE AT THE CELLULAR LEVEL IN MALE VERSUS FEMALE CELLS. THAT'S WHY I ASKED. >> GREAT POINT. >> YES, WALLY? >> SEEMS LIKE A HUGE GAP THAT CUTS ACROSS DISEASES IS MODELS FOR CENTRALIZED PAIN. NOBODY SEEMS TO WANT TO TALK ABOUT IT BECAUSE IT'S, A, DIFFICULT TO DEFINE. THERE ARE NO PHARMACOLOGIC AGENTS, THAT I KNOW OF, THAT ARE SPECIFICALLY AIMED AT THAT. BUT IT IS A HUGE PROBLEM. IT IS A PROBLEM IN MANY, MANY DISEASES THAT BEGAN AS NOCICEPTIVE INPUT, BUT THEY TRANSFORM, AND BECOME CHRONIC CENTRALIZED PAIN. EVEN POST-SURGICAL. SO IT IS A HUGE GAP. I DON'T KNOW OF ANY ANIMAL MODELS. IF THERE ARE I WOULD LIKE TO SEE THEM. YOU WOULD MAKE ONE UP FOR POST-TRAUMATIC PAIN BUT FROM NOCICEPTIVE LIKE RHEUMATOID ARTHRITIS, SICKLE CELL DISEASE, ON AND ON, I DON'T KNOW OF ANYTHING. >> IT'S A REALLY GOOD POINT. A NUMBER OF GOOD POINTS RAISED ABOUT VALIDITY, PREDICTIVE VALUE OF ANIMAL MODELS. AND THERE'S A LOT OF ANIMAL MODELS USED CONTINUOUSLY, HAVE BEEN FOR MANY YEARS, USED IN INDUSTRY AND IN ACADEMIA. AND I THINK WHERE THE FIELD IS COMING AROUND NOW IS THAT THERE ARE A LOT OF CASES WHERE WE'RE MEASURING BASICALLY SENSITIZATION TO NOCICEPTIVE INPUT BUT WE DO LESS WELL AT ASSESSING ONGOING OR SPONTANEOUS PAIN IN THE ANIMAL MODELS. A NUMBER OF MEETINGS RELATED TO PRE-CLINICAL SCREENING PLATFORM AND OTHER THINGS THAT'S BEEN A MAJOR POINT OF DISCUSSION. ONE THING THAT NEEDS TO COME OUT OF THAT IS A RIGOROUS LOOK AT THESE ENDPOINTS WE'VE USED FOR A LONG TIME, HYPERSENSITIVITY TO HEAT, TOUCH, COLD, COMPARED TO ONGOING PAIN OR SPONTANEOUS PAIN. THERE'S SOME ASSUMPTION THOSE THINGS GO TOGETHER, THE IDEA OF BACK-TRANSLATION, EVERYTHING THAT WORKS CLINICALLY IN HUMANS WORKS FOR CHRONIC PAIN IS EFFECTIVE BUT NOT NECESSARILY TRUE IN OTHER ACTION. TO WALLY'S POINT MODELS OF CENTRALIZED PAIN THERE ARE A NUMBER OF MODELS THAT SHOW TRANSITION FROM KIND OF ACUTE PHASE TO ONE WHERE THERE ARE ROBUST CHANGES NOTICE CENTRAL NERVOUS SYSTEM, THOSE ARE TARGETED BY A NUMBER OF DRUGS, THINGS WE USE CLINICALLY LIKE SNRIs ARE MODERATING CENTRAL CIRCUITS, THE QUESTION IS HOW IS THAT RELATES TO PATHOLOGY BUT THERE'S A TARGET CENTRALLY FOR SURE. ONE OF THE IMPORTANT ASPECTS I THINK OF THAT PRE-CLINICAL SCREENING PLATFORM THAT I REALLY BELIEVE STRONGLY NEEDS TO BE INFORMED BY DATA NOT IN THE PUBLIC DOMAIN, WHAT'S MENTIONED EARLIER, FOR THE PROGRAMS IN INDUSTRY THAT HAVE BEEN TRIED AND SEEM TO HAVE FAILED CLINICALLY, WHAT ARE THE DATA ON ANIMAL MODELS, PRE-CLINICAL MODELS. SO WE CAN LEARN FROM THOSE FAILURES. AND I THINK WE CAN LEARN A LOT FROM FAILURES, BUT THAT ALL NEEDS TO BE USED TO INFORM WHAT'S DONE IN THE PRE-CLINICAL SCREENING PLATFORM. >> I THINK IT WAS KEN'S IDEA, IF I REMEMBER RIGHT, TO BUILD THIS DATABASE SO NOT ONLY WE COULD LEARN BUT THE INDUSTRY PEOPLE COULD LEARN FROM EACH OTHER, AND AVOID MAKING THE SAME MISTAKES AS ANOTHER COMPANY PREVIOUSLY HAD DONE. SO THERE'S A LOT OF ENTHUSIASM ON THE PART OF THE PEOPLE WE'VE TALKED TO IN INDUSTRY, WHETHER OR NOT THE LAWYERS WILL GO ALONG WITH IT IS STILL TO BE TEST THE. EVERYBODY WANTS TO DO THIS SO WE'LL SEE WHAT HAPPENS. >> JUST QUICKLY, I HEARD THAT IT WAS A PRIORITY TO FIND NEW ANALGESICS THAT ARE NOT ADDICTIVE BUT I WONDER IF THE CANNABINOIDS WHICH THC, FOR EXAMPLE, SEEMS PRETTY CLEAR IS AN ANALGESIC, CANNABIDIOL MAYBE NOT SO SURE, BUT WHAT'S THE APPROACH TO CANNABINOIDS IN TERMS OF DEVELOPMENT? >> WELL, WE HAVE RESEARCHERS LOOKING AT THIS. THINK CERTAINLY ONE OF THE QUESTIONS THAT HAS NOT BEEN ADDRESSED CLEARLY, THERE ARE SOME SYNDROMES THAT RESPOND BETTER TO CANNABINOIDS LIKE THE PAIN FROM SPASTICITY, I DON'T THINK ANYBODY WOULD QUESTION IT. FOR CHRONIC PAIN THE QUESTION IS DO YOU BECOME TOLERANT TO THE CANNABINOID, IT'S ALSO UNCLEAR IN CERTAIN MODELS CANNABIDIOL MAY HAVE A BETTER ANALGESIC EFFECT THAN THC, THERE'S RESEARCH. A LOT OF WORK, FOR EXAMPLE, THAT WE'RE PROMOTING IS NOT JUST SO MUCH THE WORK WITH RECEPTOR AGONIST WHICH WILL LEAD TO DOWNREGULATION OF RECEPTOR BUT TO WORK WITH MODELS, ENZYMES ARE SYNTHESIZED OR DEGRADE KA CANNABINOIDS TO BUFFER, PHARMACEUTICAL INDUSTRY IS INTERESTED IN DEVELOPING. AT THE SAME TIME JONI WAS DISCUSSING, WHAT NCATS CAN BRING, ONE OF THE AREAS THAT HAS BEEN DIFFICULT FOR US TO EXPAND RESEARCH IS EXACTLY FOR CANNABIDIOL, GNP PRODUCED SUCH THAT WE CAN GIVE IT TO RESEARCHERS AND SO I THINK MY UNDERSTANDING IS THAT OUR INSTITUTES GOT STARTED TO DISCUSS FEASIBILITY OF HAVING NCATS WORK ON DEVELOPING GNP MATERIAL FOR CANNABIDIOL SO WE CAN TEST BOTH FOR ADDICTION, ANALGESIA AND ANTI-INFLAMMATORY. >> I'LL AGREE WITH THAT. ALSO GET BACK TO WALLY'S POINT ABOUT THE IDEAS LONGER-TERM EXPOSURE TO INSULT, ACUTE TO CHRONIC PAIN, HAVING MODELS. THE PROMISE OF THE HUMAN CELL BASED SYSTEM LEND THEMSELVES TO LOOKING AT THAT AT THE CELLULAR LEVEL, AND THEN WORKING TOGETHER WITH ANIMAL MODELS ONCE WE CAN GET AN IN VIVO CELL-BASED ASSAY GOING, THAT WE WOULD LOOK AT 30 DAY, 60 DAY EXPOSURE TO KEEP THE CELLS AND BIOFABRICATED MODELS ALIVE FOR THAT LONG. WE'RE ABLE TO LOOK AT THAT, THAT LENGTH OF TIME OR THAT EXPOSURE, WHATEVER THE INSULT MIGHT BE, LENDING THEMSELVES TO MOVING INTO ANIMAL MODELS TO DO FURTHER TESTING. SO I THINK THERE ARE WAYS WHICH CAN START TO RECAPITULATE THAT BETTER AS WELL. I WANTED TO MAKE SURE I CIRCLED BACK AROUND. >> I HAVE A QUESTION TO YOU AND AMIR BECAUSE ONE OF THE THINGS WE'VE SEEN IN ADDRESSING WHAT WE EXPECT IN HUMANS, IT'S CLEAR IT'S NOT JUST SENSITIVITY OF THE PAIN BUT THE PERSON CAN BE FUNCTIONALLY PERFORMING PROPERLY. SO IF WE ARE CONCEIVING OF THAT AS TARGET FOR ANALGESIA IN HUMANS, ARE WE ALSO RETHINKING OUR ANIMAL MODELS SO WE HAVE OUTCOMES THAT ARE RELATED TO FUNCTIONAL PERFORMANCE. >> A LOT OF THE SPONTANEOUS ACTIVITY MODELS IN PAIN NOW HAVE BEEN PEOPLE MOVING TOWARDS A KIND OF GETTING INTO THAT SPACE. NOW YOU HAVE THE ABILITY TO RECORD BEHAVIORS, LIKE WE NEVER COULD BEFORE, BOTH IN ANIMALS AND PEOPLE. SO ONE OF THE BIOMARKERS IN PEOPLE MIGHT BE, YOU KNOW, DOES YOUR LEFT KNEE WHICH IS GIVING YOU TROUBLE, IS IT ACTUALLY MOVING MORE THAN IT DID BEFORE THE TREATMENT? YOU COULD POTENTIALLY MEASURE THAT IN A HUMAN. AND SIMILARLY, YOU KNOW, THE PAPER I MENTIONED ABOUT TURNING OFF THE NUCLEAR CELLS, LOOKING AT THE NATURAL BEHAVIOR OF ANIMALS IN THE CAGE AND FOUND THAT THEY COULD TELL ONE SIDE WAS HIGHER THAN THE OTHER BUT DIDN'T CARE, THEY HAD THIS BEAUTIFUL DATA THAT THE ANIMAL SPENDS JUST AS MUCH TIME ON THE HOT SIDE AS NORMAL SIDE, SO I THINK GETTING BACK TO THE NATURAL BEHAVIOR I THINK THAT'S WHAT MAYBE ROB WAS SAYING IS WHERE THE TREND SEEMS TO BE GOING AS OPPOSED TO WITHDRAWAL TYPE OF NOCICEPTIVE THING RELATED TO SENSORY PATHWAY AS OPPOSED TO HOW THE ANIMAL PROCESSES AND REACTS WHICH IS WHAT GETS YOU TO FUNCTION. >> NORA, YOU MAKE A REALLY IMPORTANT POINT. ONE OF THE MAJOR RECOMMENDATIONS AT BOTH WORKSHOPS WAS NOT TO NECESSARILY GO OUT AND DEVELOP A NEW MODEL, BUT TO IDENTIFY VALIDATE ENDPOINTS THAT ARE MORE PREDICTIVE OF WHAT HAPPENS NAP HUMANS. AND WORK BACKWARDS AND FIGURE OUT WHAT WE NEED. THAT'S WHAT WE'LL FOCUS ON, PARALLEL TRACK SCREENING EFFORT TO ADVANCE OUR UNDERSTANDING OF THESE THERAPEUTICS AND DE-RISK AS WE GO FORWARD, TO DIVE IN AND FIND OUT ENDPOINTS, WHAT ARE THE MARKERS, PERHAPS BEYOND PHENOTYPE, PERHAPS BIOMARKERS THAT COULD BE REALLY ESSENTIAL TO IDENTIFYING THE EFFICACY AND PREDICTING VALIDITY OF THESE THERAPIES THAT COME INTO OUR PLATFORM. >> AND ALSO ONE POSSIBILITY TO THINK ABOUT IS MOVING INTO SOME NON-HUMAN PRIMATE LIKE THE MARMOSET MODEL WHERE NOT ONLY IS ANATURALTY SIMILAR TO HUMANS, NEUROAFFECTIVE COMPONENT MAY BE MORE SIMILAR. THERE MAY BE OPPORTUNITIES, GOING INTO NEW TERRITORY, BUT COULD BE HELPFUL. >> THAT'S COME UP IN SEVERAL OCCASIONS. WE'VE BEEN FOCUSING ON RODENTS, PARTICULARLY RATS, THAT HAS A LOT OF VALIDITY AND CROSS-SPECIES. BUT THINKING HAS BEEN TO GO SMALLER ANIMALS TO ZEBRAFISH, THAT CAN BE DONE QUICKLY, BUT ALSO PRIMATES THAT CAN BE A LOT MORE PREDICTIVE OF WHAT HAPPENS. SO WE'RE ENTERTAINING THE BROADER SPECTRUM TO FIND OUT WHERE REALLY THE SWEET SPOT IS FOR REALLY CHARACTERIZING WHAT'S AVAILABLE TO US. >> ESPECIALLY FOR BACK PAIN, SUCH A HUGE PROBLEM IN HUMANS. MARMOSET IS NOT QUITE UPRIGHT BUT MORE UPRIGHT THAN MICE. SO IT COULD BE HELPFUL ANATOMICALLY THERE. >> I GUESS FOR DEVICES I GUESS WE HAVE TO REALLY -- THAT'S A SPACE WE HAVEN'T BEEN INTO BEFORE, SO TO TRY TO THINK ABOUT HOW TO SET UP SO THAT WE CAN TEST DEVICES IN THIS PLATFORM IS ALSO SOMETHING BRAND NEW TO TRY. >> ANY OTHER COMMENTS? THANK YOU. WE CAN MOVE ALONG TO EARLY PHASE PAIN INVESTIGATION CLINICAL NETWORK, KNOWN AS EPPIC-Net, AND CLINT WRIGHT IS GOING TO BE THE PRESENTER. >> GREAT. CLINTON IS DIRECTOR OF THE DIVISION OF CLINICAL RESEARCH AT NINDS, AND WORKING WITH A TEAM TO PUT TOGETHER THIS NETWORK TO DO EARLY PHASE TRIALS OF BOTH DEVICES, BIOLOGICS AND SMALL MOLECULES. >> HI, EVERYBODY. THANK YOU FOR HAVING ME. I APPRECIATE EVERYONE BEING HERE TODAY. SO WE'LL TALK ABOUT EPPIC-Net AND THE CHARGE THAT'S BEFORE US IN TERMS OF PUTTING TOGETHER THIS NETWORK. THE GOAL WE'RE ALL FAMILIAR WITH, WE WANT TO IMPROVE THE TREATMENT OF ACUTE AND CHRONIC PAIN, BUT REDUCE THE RELIANCE ON OPIOIDS, AND WE WANT TO ACCELERATE THE EARLY PHASE TESTING OF THESE NON-ADDICTIVE THERAPEUTICS AND INCLUDE DEVICES IN THAT PROGRAM. SO, TO DO THIS WE HAVE TO DEVELOP SOLID INFRASTRUCTURE, WE NEED TO PULL TOGETHER THE CORRECT EXPERTISE, WHICH INCLUDES A LOT OF PAIN EXPERTISE, IN DIFFERENT AREAS OF THE PAIN SPACE, WE'VE GOT A LOT OF BALLS IN THE AIR. WE HAVE PUBLIC HEALTH CRISIS GOING ON, TRYING TO DO WHAT WE CAN AS QUICKLY AS WE CAN, WE'RE DOING THINGS WITH MODELS, WITH CLINICAL TRIALS, A LOT OF THINGS SIMULTANEOUSLY. I THINK IN THAT TYPE OF SITUATION WE WANT TO MAKE SURE THAT OUR MODELS, OUR INFRASTRUCTURE IS ITERATIVE, AND ABLE TO INCLUDE NEW THINGS AS WE LEARN ALONG THE WAY. THE NETWORK NEEDS TO BE A LEARNING NETWORK. YOU'LL SEE MORE OF THAT IN A MINUTE. WE ALSO WANT TO TRAIN NEW INVESTIGATORS. IT WAS SAID EARLIER THAT WE DON'T HAVE A LOT OF PEOPLE IN THIS SPACE, WE WANT TO MAKE SURE THAT WE'RE CREATING OPPORTUNITIES FOR PEOPLE TO BE BROUGHT INTO THE SPACE, AND GET INTERESTED IN PAIN, AND START TO STUDY PAIN. AND THERE'S A LOT OF OPPORTUNITIES WE SAW ONE CLINICAL TRIAL DESIGN THAT WAS MENTIONED EARLIER, THERE ARE A NUMBER OF VERY INNOVATIVE TRIAL DESIGNS THAT CAN BE USED, SOMEONE MENTIONED CLUSTER, RANDOMIZED TRIALS, AND WE SAW COMPLICATED ALGORITHM EARLIER AS WELL, AND THERE'S MANY OTHERS. THERE'S ADAPTIVE RANDOMIZATION, SO THERE ARE MANY THINGS WE CAN USE FROM THE CLINICAL TRIAL ARENA, TO PUSH THIS FIELD FORWARD. ONE OF THE THINGS THAT -- KEN AND I WERE CO-CHAIRING A COMMITTEE ABOUT A YEAR AGO, ONE OF THE THINGS THAT CAME UP FROM INDUSTRY WAS THE NEED TO HAVE VERY WELL PHENOTYPED PATIENTS. THAT'S SOMETHING THAT HAS BEEN LACKING IN SOME EFFORTS, SO WE WANT TO MAKE SURE WE HAVE WELL PHENOTYPED PATIENT COHORTS THAT WE DEFINE THOSE PAIN CONDITIONS THAT WE'RE GOING AFTER AND WE'RE ABLE TO PHENOTYPE THEM WELL. AND THEN THE PROGRAMS AND BIOMARKERS WE TALKED ABOUT, ENDPOINT DEVELOPMENT, WE WANT TO MAKE SURE WE'RE INCORPORATING THOSE INTO THE NETWORK AS WELL. SO THAT'S A PRETTY TALL ORDER. BUT I'M VERY EXCITED ABOUT IT AND I THINK THERE'S A LOT OF EFFORT GOING INTO THIS RIGHT NOW. SO THE EPPIC NETWORK INFRASTRUCTURE WILL BE SIMILAR TO OTHER CLINICAL TRIAL NETWORKS AT NINDS, WE'VE RUN THREE IN DIFFERENT SPACES, AND THIS IS KIND OF MODELS ALONG THAT. HOWEVER, BECAUSE OF THE URGENCY OF THIS WE WANTED TO BUILD IN SOME ABILITY TO BE MORE FLEXIBLE AND SOME ABILITY TO MOVE QUICKER BECAUSE ANOTHER THING WE HEARD FROM THE INDUSTRY PARTNERS WAS THAT IT'S DIFFICULT SOMETIMES TO WORK WITH PROGRAMS THAT REQUIRE LONG RUNWAYS FOR GETTING THINGS OFF THE GROUND ASSOCIATION WE TRIED TO LOOK AT THOSE OPPORTUNITIES AND CREATE FASTER FLEXIBILITY. SO, THE NETWORK WOULD INCLUDE A DATA COORDINATING CENTER, CLINICAL COORDINATING CENTER, AND THEN A BUNCH OF HUBS AND SPOKES SPECIALIZED IN DIFFERENT PAIN AREAS. I WANT TO MENTION THAT THE DATA COORDINATING CENTER WOULD ALSO ALLOW US TO DO SOME OF THE THINGS THAT WERE JUST DISCUSSED IN TERMS OF DATA SHARING AND ALLOWING DIFFERENT PROGRAMS TO PROVIDE DATA INTO THE NETWORK, THE NETWORK WOULD SUPPORT THAT REPOSITORY, AND THEN IT WOULD ALLOW FOR DATA SHARING AND TRANSFER ACROSS THE DIFFERENT INSTITUTES, FOR EXAMPLE. THE CLINICAL COORDINATING CENTER WOULD OVERSEE AND KIND OF MANAGE THE HUBS AND SPOKES, BUT THEY WOULD ALSO REALLY PULL ON THE EXPERTISE OF THOSE SPECIALIZED CLINICAL CENTERS THAT MIGHT NOT NECESSARILY BE PRESENT IN THE CLINICAL COORDINATING CENTER. SO THAT'S GOING TO BE REALLY IMPORTANT. SO THE INFRASTRUCTURE, ONE OF THE THINGS I MENTIONED EARLIER WAS THE NEED TO MOVE QUICKLY ON THIS. AND, YOU KNOW, IN OUR TRADITIONAL CLINICAL TRIAL NETWORKS, WE HAVE STANDARD REVIEW PROCESSES WHERE WE BRING IN USUALLY GRANT APPLICATIONS, SOMETIMES THEY ARE DONE THROUGH CONTRACTS, IN THE GRANT EXAMPLE WE BRING IN THE APPLICATION, IT GETS REVIEWED, MAY GO BACK TO THE APPLICANTS, WITH SOME SUGGESTIONS, THEY MAY COME BACK IN AGAIN, IT MAY TAKE A WHILE TO GET THOSE THINGS. WHAT WE WANTED TO DO HERE BECAUSE SOME OF THE APPLICANTS MAY BE FROM INDUSTRY, AS WALTER MENTIONED, THEY MAY BE FROM BIGGER COMPANIES, FROM SMALLER COMPANIES, FROM ACADEMIA, WE HAVE A LOT OF DIFFERENT -- WE WANT TO OPEN THE DOOR TO ANYBODY WHO WANTS TO BRING IN AN ASSET SO WE WANT TO CREATE A LOW BAR FOR BRINGING THOSE ASSETS IN AND BECOMING AWARE OF THEM. SO, WE HAVE SET UP A STRUCTURE TO TRY AND DO THAT. I'M GOING TO JUST SORT OF FLOW THROUGH THIS, BUT THE IDEA IS THAT WHATEVER THE ASSET IS, IF IT IS A DRUG, IF IT IS A BIOLOGIC, IF IT IS A DEVICE, IT WOULD COME IN THROUGH A TEMPLATE THAT REQUIRES NOT A LOT OF INFORMATION BUT THE BASIC AMOUNT OF INFORMATION THAT WE FEEL IS NECESSARY TO DECIDE WHETHER WE CAN MOVE FORWARD WITH MORE DETAILED INFORMATION. AND THAT WAY, THE ASSET HOLDER IS NOT HELD BACK BY A LENGTHY APPLICATION PROCESS. AND THEY CAN FIND IT EASILY ONLINE, THEY CAN ENTER THE INFORMATION QUICKLY. WE CAN BRING IT INTO THE SYSTEM. AND THEN THAT WOULD BE REVIEWED, IN AN INDEPENDENT WAY, AND USING SIMILAR ETHICAL FIRE WALLS WE USE HERE AT NIH TRADITIONALLY, AND THEN ONCE THE BASIC INFORMATION WAS ASSESSED, AND IT WAS DECIDED THROUGH THE COMMITTEES WHICH ASSETS SHOULD MOVE FORWARD TO GET MORE INFORMATION, THEN WE WOULD GO TO THE NEXT STAGE WHICH WOULD BE TO WORK WITH THE ASSET HOLDER TO DEVELOP A VERY COMPLETE VIEW OF THE ASSET, THAT'S WHAT WE'RE CALLING A DOSSIER. AND THOSE DOSSIERS WOULD COME BACK IN, BE REVIEWED VERY EXTENSIVELY, AND THEN ONCE THE DOSSIERs HAD BEEN PRIORITIZED AND DECIDED WHICH ONES WERE READY FOR PRIME TIME TO MOVE INTO A CLINICAL TRIAL, THEN WE WOULD DEVELOP -- ASK THEM TO DEVELOP A PROTOCOL. AND THE CLINICAL COORDINATING CENTER WOULD WORK WITH THE SPECIFIC SITE THAT HAD THE PAIN EXPERTISE, WHATEVER PAIN EXPERTISE THAT WAS NEEDED FOR THAT ASSET, DEVELOP A PROTOCOL, THAT PROTOCOL WOULD BE REVIEWED. AND WE WOULD MOVE FORWARD. THE IDEA OF ROLLING REVIEW TO GET THIS ACCOMPLISHED QUICKLY, NOT SOMETHING A VERY LENGTHY PROCESS. WE HOPE TO GET ASSETS IN QUICKLY, ASSESSED AT DIFFERENT LEVELS AND BE ABLE TO MOVE FORWARD. I WANTED TO GO BACK TO THE COMMENT ABOUT DATA SHARING, SO THE IDEA IS THAT EPPIC-Net WOULD HAVE THE INFRASTRUCTURE TO HOLD BIOSAMPLES THAT WOULD BE PRODUCED AS PART OF THE TRIALS, ALSO HOLD BIOSAMPLES THAT COULD BE BROUGHT BY INDUSTRY TO HELP LEVERAGE THE WORK THAT'S GOING ON, NOT ONLY IN EPPIC-Net BUT IN THE OTHER NIH PROGRAMS. AND SEVERAL OF THE OTHER NIH PROGRAMS WOULD BE ABLE TO PROVIDE DATA THAT WOULD THEN BE SCORED IN EPPIC-Net SO WE'RE SETTING UP THE INFRASTRUCTURE TO STORE THAT DATA. SO WHERE WE ARE IN THE PROCESS IS THE INFRASTRUCTURE IS READY TO BE REVIEWED IN MAY, AND WE HAVE APPLICATIONS IN ALREADY. WE PLAN TO HAVE ONE MORE ROUND OF APPLICATIONS FOR THE CLINICAL SITES AS WELL. AND THEN ONCE WE GET THE INFRASTRUCTURE FOR THE NETWORK SET UP, THEN TO FUND THE INDIVIDUAL FILES THAT WILL BE DONE USING AND OTHER TRANSACTIONAL AUTHORITY MECHANISM THAT WILL ALLOW US TO REALLY HIT THE GROUND RUNNING. WE'LL HAVE THE INFRASTRUCTURE READY TO GO. AND THEN THE TRIALS WILL BE FUNDED THROUGH THE CLINICAL COORDINATING CENTER AND THEY WILL -- WE WILL BE ABLE TO MOVE QUICKLY WITH THOSE AND BE ABLE TO MOVE THE ASSETS AROUND AS NEEDED. SO THAT'S IT. AND I'M HAPPY TO TAKE QUESTIONS. >> THANKS. ALLAN BASBAUM, DID YOU JOIN THE MEETING? >> I THOUGHT I HEARD HIM. >> OKAY. WELL, IF YOU CAN UNMUTE YOURSELF, WE CAN INTRODUCE YOU. >> HI. YEAH, IT'S ALLAN. I JUST FINISHED TEACHING STUDENTS ABOUT PAIN FOR TWO HOURS. [LAUGHTER] >> WE'VE BEEN TEACHING OURSELVES FOR A LITTLE LONGER BUT I'M GLAD YOU COULD JOIN US NOW, ALLAN. >> JUST KIDDING. >> JUST LISTENING TO THE RAMPING UP OF EPPIC-Net PRESENTATION, NOW OPENING THAT UP FOR QUESTIONS. >> I WAS JUST SAYING I WAS ACTUALLY LISTENING TO THE WHOLE MORNING SESSION WHILE I WAS DRIVING IN TO NORA'S AND YOUR TALK, TO WALTER'S TALK. IT WAS GREAT. SO THANK YOU. >> OH, THANK YOU. CLINTON, IN TERMS OF THE TYPE OF PAIN CONDITIONS THAT THESE TEN CLINICAL CENTERS ARE AIMING TO TRY TO HAVE READY TO GO WHEN SOMEBODY HAS A POSSIBLE TRIAL IN MIND, HOW'S THAT GOING TO WORK? SO SOME COMPOUND, SOME ASSET FINDS ITS WAY THROUGH THE PROCESS, TEMPLATE, DOSSIER, LOOKS GOOD, CLINICAL TRIAL DESIGN, MOST APPROPRIATE FOR DIABETIC NEUROPATHY, IT LOOKS LIKE, OR CHRONIC REGIONAL PAIN SYNDROME. WHAT WILL BE THE CIRCUMSTANCE THEN IN TERMS OF HAVING CANDIDATES ALREADY LINED UP TO ASK FOR INTEREST IN PARTICIPATING IN CLINICAL TRIAL, DOES THAT HAVE TO START AT THAT POINT? IN WHICH CASE THERE MIGHT BE A LONG TIME FOR ENROLLMENT. >> WELL, I MEAN, I THINK IT WILL DEPEND ON SPECIALIZED CLINICAL CENTERS THAT COME IN THROUGH THIS MECHANISM TO BE FUNDED. IF IT'S LIKE DIABETIC NEUROPATHY FOR EXAMPLE OR BACK PAIN, BAKED INTO THE SYSTEM, ALSO COMMON CONDITIONS, RELATIVELY EASY TO ENGAGE ALL OF THE CENTERS FOR BACK PAIN, WE COULD ENGAGE ALL THE CENTERS FOR DIABETIC NEUROPATHY, MOST OF THEM. WHEN IT COMES TO COMPLEX REGIONAL PAIN, THAT WILL BE MORE DEPENDENT ON WHO COMES IN. WE CAN -- IF WE DON'T HAVE THAT EXPERTISE CAN PARTNER WITH CTSA SITE, AS WITH OTHER SITES, AND FIND GOOD SITES WHERE WE CAN BRING THOSE PATIENTS IN. WE MAY NEED TO PUT OUT MORE CALLS AT SOME POINT FOR SPECIFIC PAIN AREAS IF WE SEE ASSETS COMING DOWN THE PIKE. >> RICK AND CHRISTIN. >> I THINK IT'S GREAT. I'M TRYING TO GET MY HEAD WRAPPED AROUND THE PROCESS. ALL THOSE ELEMENTS EXISTING IN INDUSTRY, DATA COORDINATING CENTERS AND NETWORK. YOU BRING THE INDUSTRY CRITICAL INSIGHT AND SHARED INSIGHT WHICH IS VERY CRITICAL. WHEN YOU GO THROUGH THE CLINICAL TRIAL, YOU WANT IT POWERED AND ROBUST TO ANSWER A QUESTION, THAT'S ALSO GOING TO BE REQUIREMENT FOR REGULATORY AGENCY TO APPROVE A DRUG OR DEVICE. SO IS THERE A WAY WE CAN GET THE BOTTLENECK OF REGULATORY REVIEW, LOA, MAYBE TOGETHER? BECAUSE YOU WOULD WANT TO -- UNLESS YOU WANT TO LOOK AT YOUR STUDY AS PRELIMINARY STUDY THAT HAS A PHASE 1 LEVEL POWER, THEN YOU WOULD GO TO THE PIVOTAL STUDY, THEN REGULATORY AGENCY, I'M TRYING TO FIGURE OUT IF YOU THOUGHT ABOUT THAT PROCESS TO -- MAYBE WE GET A PARTNERSHIP WITH FDA TO STREAMLINE THIS AS WELL. >> RIGHT. WE DO HAVE A PARTNERSHIP WITH FDA GOING, THAT WILL HELP. WE'LL BE IN CONSTANT CONTACT WITH THEM ABOUT IT. SO THAT'S GOING TO BE CRITICAL. ALSO THE ASSET HOLDERS WILL HAVE AN OPEN COMMUNICATION WITH FDA, ABOUT THAT, AND WHAT THE HURDLES MIGHT BE. THE HEAL PARTNERSHIP COMMITTEE, ONE OF THE OTHER COMMITTEES HAS FDA INPUT SO I THINK IT'S GOING TO BE REALLY IMPORTANT TO FIND OUT FROM THEM WHAT THE BAR IS GOING TO BE. >> THAT'S RIGHT. (INAUDIBLE). >> YEAH, ALSO SO THESE WILL BE -- PROTOCOL WILL BE DEVELOPED AND THEN YOU HAVE TO GO TO THE FDA, THEY WILL BE ON IND OR IDE, SO WE CAN'T FORCE OURSELVES ON THE FDA BUT IF WE'RE INVITED BY THE COMPANIES WE CAN GO TO THE FDA. THAT'S ACTUALLY ONE THAT WORKS BEST, WHEN WE JOIN THE COMPANIES AT THE PRE-IND OR IND MEETINGS. >> CHRISTIN AND THEN -- >> (INAUDIBLE). >> RIGHT. >> (INAUDIBLE). >> SO WE ARE HOPING THAT WE WILL BE ABLE TO WORK, LOOKING AT EFFICACY MARKERS IN A PHASE 2, THAT WOULD BE OUR TOP PRIORITY FOR THE THINGS WE WOULD LIKE TO FUND. SO WE WOULD LIKE -- BUT TO GET YOUR -- I WOULD SAY TO GET YOUR PROTOCOL APPROVED TO GO FORWARD WITH THE FDA THAT'S WHERE WE WOULD MEET WITH THE FDA AND THE INVESTIGATOR WHO OWNS THE ASSET. WE'RE HOPING THAT THE -- IN MANY INSTANCES SAFETY HAS BEEN DONE ALREADY, POTENTIALLY EVEN THE PHASE 1 WORK HAS BEEN DONE BY THE COMPANY BEFORE IT COMES IN TO US. >> IT'S POSSIBLE THOUGH THAT IF A COMPOUND COMES IN AND DOES MEET PHASE 1 WORK, YOU NEED DOSE RANGING SINGLE DOSE, MULTIPLE DOSE, IT'S NOT I DON'T THINK WHERE WE WANT TO BE TOO OFTEN BUT WE COULD THINK ABOUT WHETHER WE COULD USE SOME EVOKED PAIN MODELS IN NORMAL HUMAN VOLUNTEERS WHILE WE'RE CAPTURING PK DATA, UVB RADIATION, COLD PRESSOR TEST. I FOUND THOSE HAVE SOME UTILITY, THEY NEED A LOT MORE INVESTIGATION TO TUNE THEM UP TO MAKE SURE YOU DON'T GET A FALSE NEGATIVE, FALSE POSITIVE, YOU GO ON WITH THEM. BUT YOU COULD THINK ABOUT THAT. AGAIN, TRYING TO KILL TWO BIRDS WITH ONE STONE, GET TO THE FINISH LINE QUICKER, DO SOMETHING VALUABLE IN PHASE 1 BESIDES CHECKING WHERE YOUR TEAM X IS. >> UH-HUH, UH-HUH. >> I HAVE A QUESTION ABOUT THE WELL-PHENOTYPED PATIENT POPULATIONS OUTSIDE A FEW SPECIALIZED CENTERS AND STUDIES LIKE MAP AND OPERA. WE DON'T UNDERSTAND THE IMPORTANT FACTORS AND MEASURES IN PHENOTYPING CHRONIC PAIN IN GENERAL AND THEN IT WILL BE DIFFERENT FOR DIFFERENT TYPES OF PAIN CONDITIONS. SO I'M CURIOUS IF YOU COULD SPEAK A LITTLE BIT MORE ABOUT THAT, DOES THAT MEAN INTERNALLY YOU'RE DEVELOPING KIND OF A SET OF MEASURES THAT YOU FEEL WOULD BE USEFUL IN PHENOTYPING PATIENT POPULATIONS AS THEY COME IN OR ARE YOU LOOKING FOR CENTERS AND STUDIES, POPULATIONS THAT HAVE BEEN PHENOTYPED? >> WELL, THIS PROGRAM IS NOT SET UP TO, SAY, IMPROVE ON THAT. THE EPPIC-Net IS NOT -- WE DON'T HAVE PROGRAMS SPECIFICALLY TO ADDRESS THAT ISSUE. I THINK THERE MAY BE OTHER NIH PROGRAMS THAT ARE GOING TO BE WORKING ON THAT. IT'S IMPORTANT FOR US TO HAVE A TRANS-NIH DISCUSSION ABOUT HOW PEOPLE ARE PHENOTYPED AND HOW PAIN CONDITIONS ARE PHENOTYPED SO WE CAN BRING THAT INTO THE NETWORK. THAT'S WHAT I MEANT WHEN I SAID A LEARNING NETWORK. AS YOU POINT OUT, AS I SAID EARLIER, THERE'S THERE'S SO MUCH GOING ON AT THE SAME TIME WE'RE NOT NECESSARILY WHERE WE WANT TO BE IN THESE DIFFERENT PAIN CONDITIONS, BUT HOPEFULLY IF WE CAN BRING THAT INFORMATION IN THROUGH THE DATA SHARING, THROUGH THE REPOSITORY, WE CAN START TO USE THAT INFORMATION AS IT COMES IN, IF THAT MAKES SENSE. I AGREE WITH YOU, THAT IT'S NOT PERFECT IN TERMS OF THE PHENOTYPING AVAILABLE IN THE DIFFERENT PAIN CONDITIONS. BUT I THINK TO THE EXTENT THAT WE CAN DO GOOD PHENOTYPING, WE HAVE A LOT OF EXPERIENCE WITH RUNNING NETWORKS, YOU KNOW, COLLECTING REALLY GOOD PATIENT DATA. I THINK THAT WAS REALLY MORE WHAT I WAS TRYING TO GET AT, BECAUSE SOMETIMES THE COMPANIES OUT THERE THAT BRING PATIENTS IN THROUGH INDIVIDUAL CLINICS AND SOMETIMES THEY DON'T PHENOTYPE THE PATIENTS FULLY, THAT'S BEEN A LIMITATION OF THE TRIALS THAT HAVE BEEN RUN IN INDUSTRY TO SOME EXTENT BECAUSE IF YOU HAVE DATA THAT'S NOT VERY GOOD GOING IN, YOU'RE GOING TO HAVE NOT VERY GOOD DATA COMING OUT. >> AN IMPORTANT POINT IN THAT TO USE KIND OF THE INTERSTITIAL CYSTITIS CLINICAL TRIALS NETWORK, REGENERATION OF MAPP, MILLIONS OF DOLLARS ARE SPENT IN THE CLINICAL TRIALS NETWORK TO FIND NOTHING EFFICACIOUS, AND THAT'S WHY THEY TOOK A STEP BACK AND SAID, OKAY, WE NEED TO INVESTIGATE THIS MORE BECAUSE WE KNOW IN DIFFERENT PAIN POPULATIONS THAT THERE'S VARIABLE SUBGROUPS THAT DON'T RESPOND EQUALLY TO TREATMENT, WE DON'T UNDERSTAND UNDERLYING MECHANISMS THAT ARE AVAILABLE IN THE PHENOTYPING IS GOING TO BE THE MOST IMPORTANT PART OF IDENTIFYING A GROUP OR CLUSTERS OF PATIENTS THAT ARE RESPONSIVE TO TREATMENTS THAT YOU'RE USING IN THE NETWORK. THAT'S IN MY OPINION A VERY IMPORTANT PIECE IN HOW IT'S GOING TO BE DONE. >> REALLY GOOD POINT. >> ROB? >> I WANT TO ASK A QUESTION ABOUT SPEEDING DISCOVERY AND PROGRESS. WHAT I JUST HEARD ABOUT, WHAT'S HAPPENING WITH EPPIC-Net, WALTER CAN CORRECT ME IF I'M WRONG, DID YOU SAY THE PRESUMPTION IS PHASE 1 DOSE FINDING AND SAFETY WILL ALREADY BE COMPLETE? >> IS THAT A BAR TO ENTRY? >> I GUESS THE WAY WE PUT IT, IF WE GET 100 THINGS AND 10 LOOK GOOD, AND TWO HAVE SAFETY DATA IN HUMANS ALREADY, THOSE WILL PROBABLY GO IN QUICK. >> OKAY. >> NOW THERE'S OTHER ISSUES OF POTENTIALLY EVEN TESTING WHAT WE CALL TWO COMPOUNDS, WHERE THAT DRUG OR DEVICE MAY NOT BE THE ONE THAT ACTUALLY ENDS UP BEING COMMERCIALIZED, BUT IF THE TRIAL WORKS THAT IT WOULD OPEN UP A WHOLE NEW AVENUE FOR PEOPLE TO BUILD ON THAT AND BRING NEW THINGS IN, THAT WOULD WORK. SO THAT MIGHT BE A SECOND LEVEL. AND THEN ON THE THIRD LEVEL THERE ARE THINGS THAT LOOK REALLY GOOD, BUT THEY NEED MORE WORK, SO THEY MIGHT NEED SAFETY WORK IN PEOPLE. OR THEY MIGHT NEED ADDITIONAL CHEMISTRY, THOSE WOULD PROBABLY BE -- YOU KNOW, FACTORING THE OPPORTUNITY AND IMPACT, THOSE THINGS WOULD GO INTO PRIORITIZATION. BUT ANYWAY, GO AHEAD. >> I'M THINKING ABOUT SPACE WHERE THE INNOVATION HAPPENS, A LOT HAPPENS BEFORE THAT POINT. ONE OF THE THINGS THAT'S A BARRIER TO ADVANCING THAT STUFF IS OPPORTUNITIES WHERE WE CAN HELP ASSETS IN EARLIER PHASE, I WAS LOOKING BACK AT THE NOTES THINKING I REMEMBERED THERE'S HELP ACROSS THE WHOLE SPECTRUM BUT WHAT ABOUT THINGS IN THAT SPACE? HOW CAN THIS WHOLE PROGRAM OFFER OPPORTUNITIES TO LOWER THE BAR TO GET THINGS TO THAT NEXT LEVEL? WHAT EXISTS IN THE PROGRAM WE HAVE NOW? THERE'S DISCUSSION THERE'S NO SHORTAGE OF TARGETS BUT I SORT OF DISAGREE WITH THAT. >> YEAH. >> AND I THINK THERE'S A -- >> I DISAGREE AS WELL. >> AMIR, DO YOU WANT TO TALK ABOUT THE PRE-CLINICAL PROGRAMS THAT GET YOU TO IND? AMIR RUNS FOURA AND BLUEPRINT. >> HOW THIS CAN WORK WITH BLUEPRINT AS A WAY TO -- >> YEAH, THAT'S A REALLY GOOD POINT. WE DO HAVE MANY PROGRAMS THAT ALLOWS US TO DO PRE-CLINICAL TESTING AT EARLY PHASE CLINICAL TRIALS TO GET READY FOR PHASE 2. WE'VE BEEN THINKING ABOUT OFFERING THOSE RESOURCES BECAUSE THEY ARE CONTRACTS, WE CAN DO THAT TO THIS PROGRAM, TO GET READY FOR PHASE 2 TRIALS. SO WE CAN DO THAT. THERE'S GOING TO BE LENGTHY DISCUSSION TOMORROW ABOUT WHAT WE PROVIDE, WHAT WOULD BE MEANINGFUL TO THE COMMUNITY, WHAT TYPE OF RESOURCES ARE REALLY MUST-HAVE SO WE CAN GET MEANINGFUL PHASE 2 TRIALS. >> I THINK IN HAVING GONE THROUGH THE BLUEPRINT REVIEW PROCESS, THINKING THAT IN THE EARLY PHASE PAIN INVESTIGATION SPACE THERE'S A PERCEIVED DIFFICULTY THERE IN TERMS OF VALIDITY OF MODELS AND THINGS IN PUSHBACK, THIS IS AN OPPORTUNITY FOR HEAL - - I DON'T KNOW HOW THAT WORKS, TO PRIORITIZE THINGS FOCUSED ON PAIN OR ON OPIOID USE DISORDERS, AS A WAY TO FACILITATE THAT PROCESS OR PRIORITIZE AT THE BLUEPRINT LEVEL TO WHERE IT HELPS GET THINGS FORWARD FOR THESE HIGH PRIORITY MISSION-BASED THINGS. >> NOT ONLY NINDS HAS THE CADRE OF CONTRACTS THAT WE'RE PLANNING TO MAKE AVAILABLE FOR PROJECTS COMING IN BUT JONI HAS HER -- >> I'M STARTING A TREND. >> EXTENSIVE COLLABORATION WITHIN NCATS, WE CAN TAP INTO THEIR RESOURCES ALSO TO DO SOME OF THE EARLY TOXICOLOGY STUDIES, MANUFACTURING, AND GET US READY, ACTUALLY DO MEANINGFUL PHASE 1 TRIAL SO WE CAN BUILD A PROTOCOL AROUND AN EFFICACY TRIAL. >> NCATS COMPONENT IS THE TIME LINE OF HEAL INITIATIVE, RAMPS CAN HAPPEN AT ANY TIME. SO IF THESE PRIORITIZATIONS GET BOGGED DOWN THERE MIGHT BE SPACES NCATS CAN STEP IN AND FACILITATE PUSHING THOSE PROJECTS FORWARD WHILE OTHER PROJECTS ARE THEN MOVING AHEAD IN PHASE 2. >> I'M IMAGINING IF THAT IS ADVERTISED JUST THE WAY WE TALKED ABOUT. THAT WILL OPEN UP THE DOOR FOR SMALLER COMPANIES WITH ASSETS THAT ARE RISKY TO JUMP IN, AND ACTUALLY PRESENT THEMSELVES AS OPPOSED TO LARGER COMPANIES THAT HAVE ALREADY DE-RISKED THEIR ASSETS TO SOME EXTENT AND JUST NEED A NETWORK IN WHICH TO TEST IT. YOU WANT EARLY WINS. THAT'S A BIG COMPANY, DE-RISKED ASSETS, JUST NEED PHASE 2 AND MOVE ON. YOU WANT THAT FLEXIBILITY, SO THE BEST DISCOVERY, AS YOU JUST WERE IMPLYING, SOME OF THE BEST DISCOVERY IS IN THE HIGH-RISK SPACE. >> THOSE ARE EXCELLENT POINTS. YEAH, SURE. >> ONE LAST QUESTION FOR TIM. TO FOLLOW ON CHRISTINE'S POINT ABOUT PHENOTYPING, WHO IS HOLDING THE ISSUE OF THE ELECTRONIC MEDICAL RECORD AND THE MESS IN EPPIC VERSUS CERNER, I WAS HOPING YOU ADDRESSED THAT, YOUR EPPIC MEANS SOMETHING DIFFERENT. >> YEAH, THANKFULLY. >> LUCKY YOU. >> I MEAN THE WAY WE NORMALLY HANDLE THAT IS WITH THE DCC, SO THE DATA COORDINATING CENTER, WE USUALLY HAVE A SYSTEM BUILT IN. DEPENDS WHO THE DCC IS AND WHAT SYSTEM THEY USE BUT THE DATA COMES IN THROUGH WHATEVER SYSTEM THEY ARE USING, AND IT'S OF COURSE FIREWALLED AND EVERYTHING. NOW, WHEN YOU START TO TALK ABOUT THE ELECTRONIC HEALTH RECORD AND HOW TO PLUMB THAT AND MAKE USE OF THAT, THAT'S A SLIGHTLY DIFFERENT ISSUE WHICH I THINK NIH IS GRAPPLING WITH, YOU KNOW, IN MANY DIFFERENT REALMS. AND I THINK IT'S A REALLY IMPORTANT ISSUE BECAUSE IT IS SOMETHING THAT WE COULD REALLY LEARN A LOT FROM. BUT IN THIS SITUATION, IT'S PROBABLY A LITTLE BIT LESS. IT WILL BE APPLICABLE WHEN YOU START LOOKING AT THE LAST SLIDE, THINKING ABOUT ALL THE DIFFERENT PROGRAMS AND HOW THEY MIGHT BENEFIT, BIG SKY, BUT FOR THE PHASE 2 STUFF IT'S REALLY MORE -- EARLY PHASE STUFF I SHOULD SAY IT'S MORE PROPRIETARY SYSTEM YOU CHOOSE THROUGH THE DCC. >> ONE OTHER QUESTION ABOUT BIOMARKERS, WHAT'S YOUR NOTION HERE, ONCE YOU HAVE A COMPOUND THAT LOOKS PROMISING, YOU WANT TO RUN THE TRIAL, WHAT ARE YOU GOING TO MEASURE AND HOW ARE YOU GOING TO DECIDE? ARE WE GOING BACK TO THE USUAL ONE TO TEN SCALE OR SOMETHING ELSE IN MIND HERE? >> WELL, I THINK THAT THAT'S A GREAT POINT. SO BIOMARKERS ARE A BIG PART OF THE NETWORK. AS AN OPPORTUNITY. SO, WE WANT TO BE ABLE TO RUN BIOMARKER STUDIES AS PART OF THE NETWORK, WE HAVE EXPERIENCE DOING THAT IN OUR OTHER NINDS NETWORKS, THERE ARE OTHER NETWORKS ACROSS NIH THAT DO THAT. SO IF THERE ARE EITHER OUTCOME OR BIOMARKER STUDIES THAT CAN BE DONE IN THE NETWORK, THAT'S ONE OPPORTUNITY. THE OTHER IS IF THERE ARE BIOMARKERS THAT ARE PUTATIVE THAT EXIST IN THE BIOSAMPLE REPOSITORY THAT CAN BE TESTED THAT COME OUT OF THE TRIAL NETWORK OR COME IN FROM INDUSTRY, BECAUSE WE ARE SETTING UP THIS REPOSITORY TO TAKE IN THE BIOSAMPLES, SO THERE'S OPPORTUNITIES THERE AS WELL. >> CAN I MAKE A COMMENT? >> YES PLEASE, ALLAN. >> WELL, OBVIOUSLY THERE'S YET NO BIOMARKERS WHICH IS A BIG PROBLEM, CLEARLY ONE OF THE OBJECTIVES OF HEAL , BUT IT'S MORE THAN JUST -- THE VAS WORKS BUT THERE ARE MANY OTHER SCALES, QSP, AUTONOMIC ENDPOINTS, A VARIETY OF THINGS ONE COULD USE, BUT YOU WOULDN'T NOT DO THE STUDY BECAUSE WE DON'T HAVE A BIOMARKER. I WOULDN'T BE THAT OPTIMISTIC. MARK HUTCHERSON PRESENTED AT THE INTERNATIONAL ASSOCIATION FOR PAIN MEETING, WORKING WITH A CHEMIST DOING COMPARABLE THINGS IN CSF, I THINK THERE'S AN EFFORT THERE BUT IT'S PROBABLY ONE OF THE BIGGEST UNMET NEEDS. >> ONE OF THE OPPORTUNITIES HERE, WE RUN OUR TRIALS, CAN HAVE A SECONDARY OUTCOME SOME QST AND OTHER PUTATIVE BIOMARKERS AND CAN FOLD THEM INTO THE TRIALS AND SEE WHAT WE CAN LEARN FROM THEM, IN SPECIFIC PAIN CONDITIONS. EVEN THOUGH THEY ARE NOT THE PRIMARY FOCUS OF THE STUDY OR PURPOSE OF THE STUDY. SO I THINK WE REALLY SHOULD DO THAT. THAT'S, AGAIN, BACK TO MY POINT ABOUT ITERATIVENESS AND BEING ABLE TO LEARN AS WE GO ALONG. >> I'M SORRY I DID MISS THE TALK, I WAS TEACHING AND JUST JOINED. ARE YOU GOING TO BE GENOTYPING THE PATIENTS? >> WE'LL PROBABLY HAVE THE BLOOD. WE DO NOT HAVE GENOTYPING AS A COMPONENT AT THE MOMENT AS AN EXISTING FUNDING OPPORTUNITY BUT THE BLOOD WILL BE THERE. >> IT'S GETTING REAL CHEAP. >> YEAH, YEAH. >> WON'T TAKE MUCH. >> I THINK THERE'S CLEARLY THE DISCUSSION INDICATING THAT WE'RE TREADING ON GROUND THAT'S A LITTLE UNSETTLED, AND HOPEFULLY THE PEOPLE WHO DO THIS WORK ARE COMFORTABLE WITH THAT. BUT I THINK, YOU KNOW, THE HOPE IS THAT OVER TIME IT BECOMES MORE SETTLED SO THE PHENOTYPING AS CHRISTINE SAID, A LOT OF THESE AREAS WE DON'T HAVE GREAT PHENOTYPES BUT THEY ARE GOING TO BE FORCED TO PHENOTYPE THE PATIENTS FOR THE STUDIES, AND SO I THINK MUCH MORE KNOWLEDGE ABOUT THE PHENOTYPES WILL COME OUT OF THE TRIALS. ALSO WHO RESPONDS TO WHAT WILL ALSO COME OUT OF THE TRIALS. SO YOU HAVE AN OPTION OF DOING NATURAL HISTORY STUDIES WHICH GO ON FOR TEN YEARS AND THEN YOU TEST. WE'RE TRYING TO GO FASTER, TRYING TO INCORPORATE THE PHENOTYPING WITH THE INTERVENTIONS, BACPAC IS ANOTHER GOOD EXAMPLE. THEY ARE TRYING TO LEARN MORE ABOUT BACK PAIN BY UNDERSTANDING WHO RESPONDS AND WHO DOESN'T, WHAT KIND OF DETERMINES THE RESPONSES, BOTH MECHANISTICALLY AND PSYCHOSOCIALLY. SO WE'RE TRYING TO GET THESE INTERVENTIONS TO GET AT SOME OF THESE THINGS. >> THE MORE YOU READ IN THAT SPACE, THE MORE DIFFICULTY BECOMES, SECONDARY IDENTIFICATION OF OUTCOMES IS PROBLEMATIC. HOW YOU INTEGRATE OBSERVATIONAL DATA WE KNOW PITFALLS AROUND ESTROGENS, YOU HAVE TO TAKE THE DATA TO BUILD HYPOTHESIS YOU CAN BUILD PRELIMINARY ALGORITHM AND THEN BUILD ON THAT, IMPROVE IT OVER TIME AS YOU GET MORE DATA, PARTICULARLY MORE PHENOTYPIC DATA, BUT IT'S A SPACE THAT I THINK NIH HAS A LOT OF WORK TO DO, IT'S NOT DONE WELL BECAUSE OF THE PROBLEM OF SECONDARY DATA ANALYSIS. >> I TAKE THE ISSUE ABOUT TRYING TO COME UP WITH OUTCOME FOR PAIN, PROBABLY PRIMARY OBJECTIVE FOR THIS GROUP, IT'S AN ISSUE WE STILL USE THE VAS SCALE WHICH IS SO SUBJECTIVE. AND IF WE LOOK AT THE EXISTING INSTRUMENTS LIKE THE SCALE FOR BACK PAIN AND SO ON, THEY ARE 20 AND 30 YEAR OLD INSTRUMENTS, SOME PEOPLE USE mL 36, SOME AREAS OF THAT. IF WE WERE TO INCORPORATE THE STATE OF THE ART fMRI CORRELATE, AND DEVELOP PROCESS TO DEVELOP BETTER PAIN OUTCOME MEASUREMENTS IT WILL ELEVATE THE ENTIRE EFFORT OF THE GROUP. >> THAT'S GREAT TO KNOW. IMAGING STUDIES ARE EXPENSIVE. SO WE NEED TO KNOW WHAT IT'S GOING TO COST. >> ARE WE HANDLING ANY OF THIS THROUGH THE ACUTE TO CHRONIC PAIN TRANSITION? WILL WE GATHER SOME OF THE DATA, WALTER? >> THE ACUTE TO CHRONIC PAIN TRANSITION STUDY, WILL THIS BE A VEHICLE FOR DEVELOPING SOME OF THESE MEASURES? >> I THINK THAT THAT'S A REALLY INTERESTING THING TO THINK ABOUT, TO ACTUALLY SAY DO YOU HAVE CHRONIC PAIN, DON'T HAVE CHRONIC PAIN, THERE'S A TRANSITION THAT OCCURS, INTERESTING TO EXPLORE HOW -- WHAT HAPPENS OVER THAT TIME FRAME. I THINK IN TERMS OF THE BIOMARKER, THE LOW-HANGING FRUIT SEEMS TO BE BASICALLY MARKERS THAT RELATE TO THE HUMAN PAIN CONDITION, SO I MENTION ACTIVITY, MOVEMENT AROUND THE FREE, YOU CAN MENTION FACIAL EXPRESSION, PEOPLE WITH TIC DOLAREAUX, MAY BE THE LOW-HANGING FRUIT MOVING QUICKLY THAN WAITING SIX MONTHS, GIVING A PAIN SCORE COLLECT ONE GROUP, HOW MUCH DID THEIR ACTIVITY LEVEL CHANGE OVER THREE MONTHS, MIGHT BE BETTER THAN THE OTHER. SO I THINK I'M MORE OPTIMISTIC ON THE HUMAN BEHAVIORAL ASSESSMENT SIDE FOR EARLY BIOMARKERS. THE MRI WE KNOW THERE ARE CIRCUITS IN THE BRAIN CHANGING WITH CHRONIC PAIN, AND WITH CHANGE WHEN THE PAIN IS ALLEVIATED, AND THERE IS A GROUP THAT HAS BEEN WORKING MULTI-CENTER TO TRY AND REFINE THAT TECHNOLOGY, SO THAT IT COULD BE USEFUL IN, YOU KNOW, IN A CLINICAL TRIAL SETTING, AND WE HAVE A BIOMARKER PROGRAM WHICH WE TALKED ABOUT THIS MORNING, WE DIDN'T TALK ABOUT THIS AFTERNOON, THAT WE'LL BE TRYING TO MOVE THOSE KIND OF THINGS TO THE POINT WHERE THEY CAN BE BROUGHT IN TO THE EPPIC-Net PLATFORM. SO AS CLINT SAID WE HAVE A LOT OF BECAUSE -- A LOT OF LOT OF BALLS IN THE AIR. WE'LL HOPE TO WIN THIS BATTLE. >> THE OTHER THING THAT IS UNIQUE ABOUT THE PROJECT, ACUTE TO CHRONIC PAIN, IT WILL ENABLE US TO TRY TO IDENTIFY PERHAPS BIOMARKERS, IT BECOMES RELEVANT BECAUSE A KEY COMPONENT IS HOW DO YOU PREVENT THAT TRANSITION FROM HAPPENING. AND THEN THE OTHER ASPECT ABOUT IT, WE'RE, AGAIN, NEUROIMAGING IS ONE OF THE BIOMARKERS THAT WILL BE TESTED, IT WILL NOT BE THE ONLY ONE, BUT ANOTHER ONE THAT'S IMPORTANT, DISCUSSED BACK AND FORTH IS RELATED TO THE HETEROGENEITY OF THE PAIN SYNDROMES AND EXTENT YOU MAY BE IDENTIFYING THEM, WE MAY BE SPEAKING ABOUT NEUROPATHIC PAIN, MAY IN AND OF THEMSELVES NOT BE NECESSARILY NEUROBIOLOGICALLY HOMOGENOUS AND THROUGH ACUTE TO CHRONIC PAIN WOULD PROVIDE US THAT INFORMATION TO SEE IF BASED ON THIS IS BIOLOGIC PARAMETERS CAN COME UP WITH GROUPINGS THAT MAKE MORE PREDICTIVE SENSE OF OUTCOMES. >> THERE WAS ONE OTHER -- A COUPLE OTHER THINGS THAT CAME OUT OF DISCUSSIONS FROM THE PAIN RESEARCH GROUP THAT MET FOR ALMOST TWO YEARS WITH LINDA. AND IT TENDS TO BE FORGETTEN, WE ASSUME WE'RE TALKING ABOUT TRANSITION FROM ACUTE TO CHRONIC BUT THERE MAY BE INDIVIDUALS, IT'S CHRONIC FROM THE GET-GO. IT'S NOT A QUESTION OF AN ACUTE TRANSITION THAT OBVIOUSLY THAT'S THE ASSUMPTION BUT WE REALLY DON'T KNOW IT MIGHT BE THERE ALL THE TIME. THE OTHER COUPLE INTERESTING THINGS THAT CAME OUT OF THAT WHICH I THOUGHT WERE PROVOCATIVE, FOR EXAMPLE, IN PHN, POSTHERPETIC NEURALGIA, THE THING I LEARNED, I DIDN'T KNOW THIS, CHILDREN WHO GET SHINGLES ALMOST NEVER TRANSITION TO PHN. IT'S ONLY OLDER ADULTS AND SO THE QUESTION OF RESILIENCE COMES IN, OBVIOUSLY OTHER FACTORS CONTRIBUTING. SO I THINK WE NEED TO SORT OF THINK OF THE TRANSITION FROM ACUTE TO CHRONIC, FAR MORE COMPLEX THAN HERE IT IS, NOW IT'S CHRONIC. >> THANKS, ALLAN. >> SO, YES, TOTALLY. AND I THINK ESPECIALLY FOR MUSCULOSKELETAL PAIN I THINK WE SHOULD NOT FORGET THE MUSCULOSKELETAL TISSUES, CHRONIC MUSCULOSKELETAL PAIN HAS A CENTRAL NERVOUS SYSTEM COMPONENT, I THINK IMAGING OF STATIC AND DYNAMIC, LOOKING AT TISSUE MOBILITY, MUSCLE FUNCTION, REALLY UNDERSTANDING THAT AS THE PATIENT DOES TRANSITION TO CHRONIC PAIN, VERY IMPORTANT. >> COLLECT ALL THE DATA YOU CAN, ABSOLUTELY. IT'S BEEN A GREAT DISCUSSION OF THIS EPPIC-Net PROPOSAL. I HOPE YOU GET THE SENSE WE'RE KIND OF MARCHING IN THESE THREE PROPOSALS THIS AFTERNOON FROM THE PRE-CLINICAL TO EARLY CLINICAL AND NOW WE'RE GOING TO PAIN ERN, MORE IN THE PAIR ACTIVE EFFECTIVENESS ZONE. JANE ATKINSON IS GOING TO TALK TO US ABOUT THAT. BY THE WAY, SOME OF THE QUESTIONS YOU ASKED, HOW WE'RE GOING TO PRIORITIZE POSSIBLE COMPOUNDS TO FIT INTO EPPIC-Net, THAT IS GOING TO BE VERY MUCH THE TOPIC FOR TOMORROW WHEN THE HEAL PARTNERSHIP COMMITTEE WHICH I TOLD YOU ABOUT THIS MORNING, WHICH IS CHARGED WITH THIS EFFORT TO SIFT THROUGH THE POSSIBLE ASSETS THAT MIGHT BE INVESTED IN WILL BE TRYING TO FIGURE OUT HOW TO DO THAT PRIORITIZING SETTING UP THE TEMPLATE MODEL AND FIGURING OUT HOW FOR ONES TO LOOK PROMISING TO GET THE FULL DOSSIER, REVIEWS, WHO TO PLACE OUR BETS. THE GROUP WILL REPORT TO YOU, THREE OF YOU ARE ON IT, A DEEPER DIVE THAN WE OBVIOUSLY ARE ABLE TO DO WITH THE PLENARY GROUP HERE TODAY BUT REST ASSURED THERE'S A LOT OF EFFORT PUT INTO TRYING TO MAKE THOSE PRIORITY DECISIONS WITH THE ASSETS PUT FORWARD. WE EXPECT THERE WILL BE QUITE A LOT. I TAKE THE POINT ABOUT ANYTHING WE CAN DO TO TRY TO FREE UP CONTRIBUTIONS FROM SMALL COMPANIES THAT MAY NOT HAVE GOTTEN THEIR COMPOUND ALREADY TO THE POINT OF BEING READY FOR PHASE 2, WELL, WE SHOULD NOT MISS THE CHANCE TO SEE WHAT'S THERE. AND IT WAS GOOD TO HEAR SOME OTHER POSSIBLE WAYS WE MIGHT ADDRESS THINGS STILL PRE-CLINICAL BUT LOOK REALLY PROMISING AND WE WOULD NOT WANT TO MISS THAT. THANKS FOR THAT WISE ADVICE. OFF TO YOU, JANE ATKINSON FROM NCATS. >> IT GIVES ME PLEASURE TO TALK ABOUT THE PAIN MANAGEMENT EFFECTIVENESS RESEARCH NETWORK, PAIN ERN, BECAUSE THAT'S A MOUTHFUL. THIS IS THE TRANS-NIH EFFORT AND CO-LED BY NINDS AND NCATS BUT LINDA PORTER, MY COMPADRE, IS NOD ABLE TO JOIN US TODAY. SO, THE GOALS OF THIS PROGRAM ARE TO COMPARE EFFECTIVENESS OF EXISTING THERAPIES, OR NOVEL APPROACHES FOR DELIVERING CURRENT THERAPIES, TO PREVENT AND MANAGE PAIN WHILE REDUCING RISK MUCH ADDICTION. WE WANT TO STRENGTHEN AND INFORM OUR CURRENT PRACTICE-BASED GUIDELINES FOR PHARMACOLOGIC AND NON-PHARMACOLOGICAL METHODS TO MANAGE PAIN. WE WANT TO GENERATE GUIDELINES BOTH FOR MANAGEMENT OF ACUTE OR CHRONIC PAIN IN PEOPLE ACROSS DIVERSE COMMUNITIES, PROVIDE PATIENTS AND PROVIDERS WITH SUITE OF EFFECTIVE STRATEGIES, IF ONE STRATEGY DOESN'T WORK WHAT SHOULD BE MY NEXT STRATEGY TO TRY. AND IMPROVE QUALITY OF LIFE FOR PATIENTS AND THEIR FAMILIES. SO, WHY DO WE ESTABLISH THE HEAL -- THE PAIN ERN? THERE'S INEFFICIENT HIGH QUALITY EVIDENCE FOR EFFECTIVENESS OF MANY STRATEGIES THAT ARE CURRENTLY USED TO MANAGE PAIN. AND THIS WAS HIGHLIGHTED IN AT LEAST THREE HIGH QUALITY SYSTEMATIC REVIEWS. THE GUIDELINE FOR PRESCRIBING OPIOIDS FOR CHRONIC PAIN, AHRQ SYSTEMATIC REVIEW FOR NON-PHARMACOLOGICAL TREATMENT FOR CHRONIC PAIN, AND THE FEDERAL PAIN RESEARCH STRATEGY. SO, TO RAPIDLY RESPOND TO THIS NATIONAL NEED, WE ARE GOING TO CONDUCT THE TRIALS IN WHAT WE CALL THE HEAL PAIN MANAGEMENT ERN, WHICH WILL BE BUILT ON TOP OFS EXISTING INFRASTRUCTURE THAN NCATS HAS THROUGH CLINICAL AND TRANSLATIONAL SCIENCE AWARDS PROGRAMS, ALLOWING NIH TO ADDRESS PAIN QUESTIONS FROM MULTIPLE CONDITIONS IN ONE NETWORK. WE HAVE RELEASED FUNDING OPPORTUNITY ANNOUNCEMENTS SOLICITING TRIALS, NECESSRY TO CAME UP WITH A DEFINITION FOR "EFFECTIVENESS. WE'RE CALLING IT THE CONDUCT AND SYNTHESIS OF RESEARCH COMPARING BENEFITS AND HARMS OF DIFFERENT INTERVENTIONS AND STRATEGIES TO PREVENT, TREAT, MANAGE PAIN CONDITIONS IN REAL-WORLD SETTINGS. SO WHAT INTERVENTIONS WOULD WE CONSIDER? WE'LL TAKE ALMOST ANYTHING. THIS IS A VERY COMPREHENSIVE LIST. BUT WE'RE NOT SUPPORTING TRIALS WHOSE PRIMARY PURPOSE IS TO GAIN APPROVAL BY THE FDA FOR NEW DRUG OR DEVICE SO NO PHASE 3 PIVOTAL CLINICAL TRIALS. OUR STRUCTURE, WE'LL HAVE INDIVIDUAL AWARDS FOR STUDY TEAM AND COST FOR PARTICIPANTS, ADDRESSING QUESTIONS ACROSS MULTIPLE NIH INSTITUTES, CENTERS AND OFFICES. IF YOU READ THE RFA WE RELEASED, ALMOST EVERY I.C. PUT LANGUAGE INTO THAT RFA. WE'RE ALSO GOING TO INCORPORATE TWO ADDITIONAL TRIALS INTO THE ERN, AGAIN LEVERAGE SOME NIH INVESTMENTS WE'VE ALREADY MADE. ONE WILL COME FROM MATERNAL-FETAL MEDICINE UNIT OF THE HEALTH AND HUMAN DEVELOPMENT, THE OTHER FROM THE VERY BROAD WIDE-REACHING NCI COMMUNITY ONCOLOGY RESEARCH PROGRAM. THE NCATS TRIAL INNOVATION NETWORK WHICH IS AN EXISTING NETWORK TO SUPPORT CLINICAL TRIALS, WHICH IS INTEGRATED INTO THE CTSA PROGRAM, WILL PROVIDE CLINICAL AND BIOSTATISTICAL COORDINATION, SUPPORT FOR STUDY RECRUITMENT. AND WE WILL INCORPORATE PAIN EXPERTS INTO OUR EXISTING INFRASTRUCTURE. THE TRIALS WILL BE CONDUCTED WITHIN THE CTSA PROGRAM NETWORK WHICH INCORPORATES 200 CLINICAL SITES, AND OTHER CLINICAL SITES IDENTIFIED BY TRIAL STUDY TEAMS, ALLOWING RECRUITMENT OF PATIENTS WITH MULTIPLE CONDITIONS. THIS IS A LIST OF WHAT A TRADITIONAL CLINICAL COORDINATING CENTER AND DATA COORDINATING CENTER WOULD PROVIDE FOR LARGE NET WORK. BUT I WANT TO POINT OUT TWO ASPECTS OF THIS STRUCTURE THAT I THINK WILL BENEFIT US. THE FIRST IS WE WILL HAVE RECRUITMENT AND RETENTION PLANS DEVELOPED BEFORE THESE TRIALS ARE LAUNCHED, WITH RECRUITMENT INNOVATION CENTER HEADEDDED BY CONSUELA AND PAUL, CONDUCTING STUDIOS WITH PATIENTS, POSSIBLE PARTICIPANTS, POSSIBLY THEIR FAMILIES, BEFORE THE TRIAL DESIGNS ARE FINALIZED TO MAKE SURE THESE TRIALS MEAN SOMETHING TO THESE POSSIBLE PATIENTS WHO WOULD ENROLL IN THE TRIALS. AND SECONDLY, WE WILL HAVE THE ABILITY TO ADD ADDITIONAL SITES AS NEEDED THROUGH THE CTSA PROGRAM HUBS. PART OF THE TRIAL INNOVATION NETWORK IS WE HAVE TRIAL INNOVATION NETWORK LIAISON TEAMS AT EACH CTSA PROGRAM, WE'VE ALREADY SET UP A WEBSITE, AND PROCESS FOR SOLICITING ADDITIONAL SITES IF AN INVESTIGATOR SUBMITS A REQUEST. AND THE SITES WILL USE ELECTRONIC COHORT ASSESSMENT TOOLS TO SEE WHAT POSSIBLE PARTICIPANT POPULATION MIGHT BE AND THEN TRY TO FIND A LOCAL P.I. TO SEE IF THEY ARE INTERESTED. WE CAN RAPIDLY ADD NEW SITES AS NEEDED. SO THIS SCHEMATIC SHOWS HOW AN INDIVIDUAL STUDY TEAM WILL WORK IN THIS INFRASTRUCTURE. OUR PINK CIRCLE IS THE INDIVIDUAL STUDY TEAM WITH THE TRIAL DESIGN AND THEIR INDIVIDUAL AWARD. THAT DESIGN WILL BE FINALIZED BY THE TRIAL INNOVATION NETWORK THAT WILL PROVIDE THE CLINICAL COORDINATION, DATA COORDINATION, WE ALSO HAVE THREE SINGLE IRBs WE SPONSOR IN TRIAL INNOVATION NETWORK. AND THE ABILITY TO ADD THESE ADDITIONAL CLINICAL SITES. USING THE CURRENT INFRASTRUCTURE, THE TIM WILL INTERACT WITH THE CTSA CLINICAL SITES AND NON-CTSA CLINICAL SITE THEY WANT TO BRING IN IN OF IF THEY USE THE MASTER AGREEMENT FOR THE TRIAL INNOVATION NETWORK STUDIES SO WE CAN RAPIDLY BRING SOMEBODY ON. AND THEY HAVE TO AGREE TO THE SINGLE IRB POLICY. SO THIS IS OUR YEAR IN WHAT LOOKS LIKE A SIMPLE DIAGRAM, NOT THAT SIMPLE. THE TRIAL APPLICATIONS HAVE BEEN SUBMITTED THAT WERE SOLICITED THROUGH RFA, NS 19021, WE'RE WAITING FOR REVIEW OF THAT, THEY WILL BE PEER REVIEWED, OUR COLLEAGUES AT NCI AND NICHD ARE WORKING WITH TWO NETWORKS TO DEVELOP THEIR STUDY CONCEPT, CLINICAL TRIAL STUDY CONCEPTS, THOSE WILL GO THROUGH THEIR EXTERNAL SCIENTIFIC REVIEW PROCESS. THOSE PEER-REVIEWED DOCUMENTS WILL GO TO OUR TRANS-NIH SCIENTIFIC TREMENDOUSES. -- TEAMS. OUR JOB WILL BE EVALUATE AND PRIORITIZE AND WORK WITHIN OUR INSTITUTES TO IDENTIFY THE KNOWLEDGE GAP WE BELIEVE IS ADDRESSED BY A PARTICULAR TRIAL. THOSE EVALUATIONS WILL COME TO THIS GROUP SO YOU'RE GOING TO BE HEARING FROM US AGAIN IN AUGUST. AND THEN THEY WILL GO TO THE DIFFERENT IC COUNCILS AND FINALLY TO THE NIH HEAL EXECUTIVE COMMITTEE. AND THE TRIALS MUST BE FUNDED BY THE END OF SEPTEMBER OF 2019. IT WILL BE A BUSY YEAR. WHERE WE ARE, OUR SOLICITATION FOR THE INDIVIDUAL TRIALS WAS RELEASED IN EARLY DECEMBER. THAT SOLICITATION HAS ALREADY WE WILL BE COMING BACK TO YOU, AS I SAID, IN AUGUST. THE COUNCIL SECONDARY REVIEW IN SEPTEMBER OF 2019, THE PLANNING YEAR, A PHASED AWARD, UG3, A YEAR, FOR PLANNING A TRIAL. UH3 YEARS THEY CAN HAVE UP TO FOUR, FOR IMPLEMENTATION OF THE TRIALS. THE PLANNING YEAR WILL BEGIN OCTOBER 2019, A KICKOFF MEETING IN NOVEMBER OF 2019 FOR ALL OF OUR AWARDEES. AND ALL THE NIH STAFF MANAGING THESE TRIALS. SO THERE WAS A QUESTION ABOUT INTEGRATON AND DATA SHARING. OUR GOAL IS TO BE ABLE TO INTEGRATE THE PAIN ERN WITH THE OTHER HEAL CLINICAL RESEARCH NETWORKS. WE HAVE REGULAR MEETINGS OF THE NIH STAFF OVERSEEING THE TRIALS, AS WAS DESCRIBED EARLIER THIS MORNING. WE WANT TO HAVE STANDARDIZATION ACROSS THE NETWORKS AS MUCH AS POSSIBLE, AND APPROPRIATE, USING VALIDATED PATIENT-REPORTED OUTCOMES. WHEN WE TALK ABOUT IT TAKES 17 YEARS FOR AN EFFICACIOUS TREATMENT TO BE ADOPTED BY PRACTICE., WE'RE ALREADY SPENT QUITE A BIT OF TIME AND RESOURCES VALIDATING AND NOW IT'S TIME TO IMPLEMENT THEM. WE WANT TO USE COMMON DATA ELEMENTS AS MUCH AS POSSIBLE. I THINK WE SHOULD ALSO TRY TO USE COMMON DATA STANDARDS AS MUCH AS POSSIBLE, IT MAKES COMBINING THE DATA SO MUCH EASIER. AND SO THE PAIN ERN, THE TIN, TRIAL INNOVATION NETWORK, WAS ALREADY GIVEN MONEY TO DEVELOP SYSTEMS THAT ARE USING THE CDISC STANDARDS, SO WE'LL BE USING THOSE FOR ERN STUDIES AND SHOULD USE COMMON ADVERSE EVENT CODING SO WE CAN LOOK AT THE ADVERSE EVENT PROFILE CONSISTENTLY ACROSS OUR TRIALS. AT THE END OF THE TRIALS THIS DATA WILL BE DEPOSITED INTO THE EPPIC-Net CENTRAL DATA REPOSITORY, FOR FUTURE PUBLIC USE. WE'RE ALSO ASKING INVESTIGATORS WHO PLAN TO COLLECT BIOSPECIMENS TO SEND WHATEVER THEY DON'T USE IN THEIR STUDY TO THE CENTRAL DATA REPOSITORY FOR ALSO FUTURE PUBLIC USE. SO, I WILL BE HAPPY TO ENTERTAIN QUESTIONS. >> JANE, THANKS A LOT. QUESTIONS, COMMENTS? >> I HOPE THE MDWG, THAT'S YOU, GET THIS SENSE THIS IS A PARTICULARLY IMPORTANT ROLE WE'RE GOING TO BE ASKING YOU TO PLAY COME ABOUT AUGUST, BECAUSE WE KNOW WE'RE GOING TO GET MORE TRIAL APPLICATIONS THAT SCORE WELL THAN WE CAN PROBABLY AFFORD TO FUND BECAUSE THESE ARE NOT CHEAP. EVEN THOUGH THIS IS CAPITALIZED, IT'S NOT GOING TO DO EVERYTHING THAT COMES THROUGH AND LOOKS GOOD TO PEER REVIEW. SO HERE'S -- I'VE BEEN SAYING THE WORD "BALANCE," PARTICULARLY IN THIS CASE WE'LL WANT TO BE SURE WE'RE DOING SOMETHING ALONG THOSE LINES. WE DON'T WANT ALL TRIALS FOCUSED ON DIABETIC NEUROPATHY OR TMJ PAIN. WE WANT TO FIGURE OUT HOW TO DIVERSIFY, THAT DOESN'T ALWAYS TURN OUT AS OUTCOME AFTER PEER REVIEW. THIS IS WHERE YOUR INSIGHTS INTO HOW WE CAN BE SURE TO GET MAXIMUM BENEFIT FROM THE DOLLARS WE HAVE WITH THE TRIALS WE'RE ABLE TO SUPPORT ARE GOING TO BE IMPORTANT, AND THAT IS THE WAY WE'RE GOING TO PRESENT THIS TO YOU IN AUGUST AT THAT POINT THERE WILL BE A LOT MORE DETAIL OBVIOUSLY ABOUT WHAT WILL HAVE HAPPENED BY THAT TIME WITH REVIEW AND HOW NCATS AND NINDS ARE PLANNING TO STAND THESE THINGS UP BUT WE STILL WILL NEED YOUR HELP FIGURING OUT WHETHER WE'VE GOT THE MIX RIGHT. IS THAT FAIR, JANE? >> VERY GOOD POINT. NOT JUST WITHIN OUR OWN NETWORK, WE'LL HAVE RFAs FOR NEW DEVICES, WHAT ARE THEY FOCUSED ON? MULTIPLE WAYS TO BRING IN CLINICAL TRIALS THAT MAY ADDRESS THE SAME PAIN CONDITION. >> YES. >> SO, THIS SOUNDS TERRIFIC, AS A WAY OF REALLY BRINGING THE DATA TOGETHER AND HARMONIZING. SOUNDS LIKE A LOT OF EFFORT TO HARMONIZE THE ASSESSMENT PROTOCOLS AND SO ON. THAT SOUNDS GREAT. I'M NOT TOO FAMILIAR WITH THESE KINDS OF CLINICAL TRIALS, SO I'M WONDERING WHAT'S THE TIMELINE? WHEN WOULD THE DATA TYPICALLY BE SHARED? >> WELL, YOU CAN'T COMPROMISE TRIAL INTEGRITY. >> WELL, OBVIOUSLY. >> RIGHT. I GUESS BEING A VERY -- IF WE WANT TO BE OPTIMISTIC, FIVE OR SIX YEARS. >> SORRY? >> FIVE OR SIX YEARS. TYPICAL TIMELINE FOR CLINICAL TRIAL THAT ENROLLS SIX, FIVE, SIX HUNDRED PEOPLE, IS, I WOULD SAY, FIVE YEARS. >> I WASN'T QUITE SURE WHETHER THE DATA WERE BEING CENTRALLY CAPTURED. >> IT IS. >> OKAY. >> ONE DATA SYSTEM. >> SO, DOES THAT MEAN THAT SOME PARTICULAR DATA ELEMENTS COULD BE MINED FOR SOME PURPOSES? NO? >> AHEAD OF TIME? >> YEAH, I MEAN I WAS TALKING ABOUT THE POSSIBILITY OF, YOU KNOW, LIKE WE'VE TALKED ABOUT THERE BEING LOW PHENOTYPE AND GENOTYPE INFORMATION AVAILABLE, IF YOU'RE TRYING TO HAVE PEOPLE AGGREGATING ACROSS THESE DIFFERENT INITIATIVES PULLING OUT PARTICULAR DATA ELEMENTS THAT MIGHT ALLOW YOU TO HAVE A BETTER LOOK AT THE HERITABILITY OF A CERTAIN PHENOTYPE OR SOMETHING LIKE THAT, SO IS THE IDEA THAT NONE OF THE DATA, EVEN THOUGH CENTRALLY CAPTURED, WOULD BE AVAILABLE TO ANYONE UNDER ANY CIRCUMSTANCES UNTIL THE END OF THE CLINICAL TRIALS, FIVE OR SIX YEARS DOWN THE LINE? >> GO AHEAD, RICHARD. >> OBVIOUSLY THERE ARE ELEMENTS YOU CAN'T EXPOSE BECAUSE OF TYPE 1 ERROR ISSUES WHICH IS HOW MANY TIMES CAN YOU TEST A RESULT. SO PRIMARY POINT OF THE STUDY FOR EXAMPLE CAN'T BE LOOKED AT EARLY. THERE WOULD BE OPEN TO THE PUBLIC BECAUSE IT WOULD BE MASSIVE PROBLEM. BUT YOUR CONCEPT OF HAVING METADATA, OTHER DATA THAT DON'T, YOU KNOW, GO TO PRIMARY AND SECONDARY PRE-SPECIFIED ENDPOINT ANALYSIS SOUNDS LIKE SOMETHING WE COULD DO. THAT MIGHT BE WHAT YOU'RE TALKING ABOUT, THERE MIGHT BE ELEMENTS OF RECRUITMENT, CHARACTERISTICS OF PATIENTS, MAY NOT BE SO CRITICAL IN THE PRIMARY AND SECONDARY ANALYSIS WHICH WOULD HAVE TO BE HELD TOGETHER. THE OTHER ELEMENT IS SHARING COMPONENT, NATIONAL ACADEMY OF MEDICINE, THE GENERAL CONSENSUS THEY GO THROUGH STAGES ABOUT SHARING. PEOPLE DON'T SHARE MUCH NOW. BUT THE GENERAL CONSENSUS NOW IS THAT AUTHORS WOULD LIKE TO HAVE THEIR DATA AVAILABLE FOR ABOUT SIX MONTHS TO TWELVE MONTHS BEFORE THEY SHARE SO THEY CAN GET IT PUBLISHED AND SUBMIT FOR JOURNALS, IT'S A PROCESS YOU HAVE TO THINK ABOUT, MAYBE WE'LL GET TO THE POINT TO SHARE IMMEDIATELY BUT THE PRACTICAL NEXT STEP IS PROBABLY GOING TO BE TO HOLD DATA FOR MAYBE UP TO A YEAR BEFORE SHARED, AFTER THE TRIALS FINISH, FOR THE SENSITIVE DATA. >> OF COURSE clinicaltrials.gov WILL APPLY HERE. SO ALL OF THE SUMMER RESULTS WILL NEED TO BE DEPOSITED WITHIN ONE YEAR AFTER COLLECTION OF LAST DATA POINT UNLESS THERE'S AN EXEMPTION REQUESTED AND RECEIVED SO THAT'S ANOTHER STIMULUS TO MOVING ALONG WITH DOING THE ANALYSIS AND GETTING THE PUBLICATION WRITTEN. OTHER COMMENTS? NORA? >> YEAH, THIS IS SOMETHING THAT I ALWAYS ASK MYSELF. IN TERMS OF PARTICULARLY SINCE WE'RE DOING THESE THINGS, IT TAKES FIVE OR SIX YEARS, MY PERSPECTIVE IS DOES IT HAVE TO TAKE FIVE OR SIX YEARS? IS THERE SOMETHING WE CAN DO TO ACCELERATE IT? WHAT WE'VE DONE IN SOME INSTANCES TO ACCELERATE, FOR EXAMPLE, DEVELOPMENT OF TRIALS IS PUT MUCH MORE MONEY IN A SHORTER PERIOD OF TIME PROVIDING THE MECHANISM TO RECRUIT A LARGER SAMPLE SIZE, FASTER, SO YOU CAN OBVIATE THE VERY LONG TURNAROUNDS, AND I THINK I MEAN WE SHOULD THINK ABOUT IT. IS THERE SOMETHING THAT WE CAN DO TO ACCELERATE? >> I THINK -- SO I HAVE TWO THOUGHTS ON THAT. SOMETIMES I GET NERVOUS WHEN I SEE THESE TRIALS THAT HAVE 40 SIDES, HOW CAN YOU CONTROL QUALITY? ISN'T IT BETTER TO HAVE FEWER SITES, HIGHER ENROLLERS, PEOPLE KNOW HOW TO DO IT? BUT IF WE'RE TALKING ABOUT CHRONIC PAIN, AND WE'RE TALKING ABOUT SOMETHING THAT IS A FAIRLY SIMPLE QUESTION, THEN I DO AGREE WITH THAT MODEL. THAT WE NEED TO PUT A LOT MORE RESOURCES IN, GET CLINICS INVOLVED, ENROLL QUICKLY, WE PROBABLY WILL HAVE OUTCOMES COLLECTED SIX MONTHS AFTER ENROLLMENT. MAYBE A YEAR. BUT THESE SHOULD NOT BE TRIALS THAT HAVE A LONG, LONG OBSERVATION. BUT I THINK ALSO YOU HAVE TO THINK ABOUT NOT OVERWHELMING THE CLINICAL AND DATA COORDINATING CENTER AS YOU RAMP UP, DOING THINGS AT A PACE FOR WHICH YOU CAN KEEP QUALITY. YOU KNOW, I DON'T THINK WE WANT TO -- AND THAT'S SOMETHING YOU JUST HAVE TO DO BY TITRATION. ALSO WE'RE GOING TO BE STARTING SEVEN TRIALS AT ONE TIME. SO WE WILL HAVE TO -- IT'S AN ALL-HAND-ON-DECK APPROACH, WE DO HAVE FIVE DATA COORDINATING CENTERS THAT WE CAN PULL FROM IN THE TRIAL INNOVATION NETWORK, BUT STILL WE HAVE TO MAKE SURE THAT WE DO THINGS SO THAT WE CAN TRUST THE DATA THAT WE COLLECT. I KNOW WE ALWAYS HAVE IMPATIENT FOR TRIAL RESULTS. >> NO, I MEAN I THINK THIS IS -- WE SHOULD ALWAYS BE IMPATIENT. MY PERSPECTIVE THERE'S AN URGENCY FOR MANY THINGS. BUT I ALSO THINK IN TERMS OF, FOR EXAMPLE, WHEN ONE APPLIES PUTTING MORE RESOURCES IT IMPLIES PUTTING MORE RESOURCES IN THE DATA COORDINATING CENTER. AND DOING THIS IN A MORE EXPEDITIOUS FASHION IN NO WAY SHOULD BE IMPLYING THAT IT WOULD BE LESS QUALITY, NEEDS NOT BE. TWO, WE NOW HAVE ACCESS TO PLATFORMS WE DIDN'T HAVE BEFORE SO YOU CAN HAVE OVERSIGHT AT DISTANCE WITH GREAT ACCURACY, WE CAN USE NEW TECHNOLOGY TO AC SELLING -- ACCELERATE. I THROW AT YOU BECAUSE I THROW AT MYSELF ALL THE TIMES, WHAT CAN WE DO. >> WE WON'T BE DOING ON-SITE MONITORING FOR EVERY SITE. THESE ARE EFFECTIVENESS TRIALS. WE'LL BE USING ELECTRONIC MEANS TO GENERATE DATA REPORTS TO SEE WHICH SITES WE NEED TO GO OUT AND VISIT. THE QUALITY OR THE RISK BASED MONITORING MODEL NOW GAINING A LOT OF FAVOR, SO -- AND PROBABLY REMOTE TRAINING OF STUDY PERSONNEL AS MUCH AS POSSIBLE, WEB-BASED TRAINING. MAXIMIZING TOOLS TO GET SITES UP AND GOING AS SOON AS POSSIBLE AND ACCELERATE ENROLLMENT. >> JANE, CAN YOU TALK ABOUT THE BIOSPECIMEN COLLECTION AND STORAGE THAT WILL HAPPEN? IS THAT GOING TO BE CONSISTENT ACROSS THE TRIALS? >> NO. >> OKAY. >> THE WAY THE RFA WAS WRITTEN WAS IF SOMEBODY WANTED TO COLLECT A BIOSPECIMEN AND LOOK AT IT, INSIDE A CYTOKINE MARKER AS SECONDARY OUTCOME, WOULD COLLECT THOSE, DO THEIR TESTING, AND WHEN THEY ARE DONE WITH TESTING THAT WOULD BE SHIPPED TO THE CENTRAL BIOREPOSITORY. BUT AT THE MOMENT WE HAVE NOT COLLECTED -- WE HAVE NOT CONSIDERED COLLECTING LIKE AT LEAST THE SAMPLE FOR DNA FROM EVERYBODY. BUT THAT, YOU KNOW, SOMETHING WE CAN ADD. >> I WAS CURIOUS, SOMETIMES IT'S WORTH THINKING ABOUT THAT DOWNSTREAM TESTS THAT YOU CAN DO ON A SPECIFIC INDIVIDUAL IN THE CLINICAL TRIAL, YOU HAVE SO MUCH INFORMATION ON THEM ALREADY, TO THINK ABOUT THE CELLULAR BASED ASSAYS YOU COULD DO OR GENETICS YOU COULD DO MIGHT ALSO PAY DIVIDENDS. >> YEAH, QUICKLY, SORT OF A HIGHER LEVEL COMMENT, THINKING ABOUT THE RANGE OF THESE RFAs AND OVERLAPS, I THOUGHT I HEARD REVIEWERS COULDN'T BE INVOLVED IN HEAL INITIATIVE IF THEY WERE REVIEWERS, WONDERED IF THAT WAS TRUE OR HOW, GIVEN THE REAL EXPANSE OF DOMAINS YOU'RE GOING TO FIND REVIEWERS WHO AREN'T AT SOME LEVEL INVOLVED IN A LOT OF THESE. >> WOULD YOU CARE TO COMMENT? >> I DON'T THINK THAT IT'S TRUE ACROSS ALL OF HEAL . I THINK IT'S PROBABLY -- I CAN'T COMMENT WHETHER IT'S ONLY FOA BY FOA, BUT CERTAINLY WE CAN'T GET AWAY WITH EXCLUDING EVERYONE APPLYING FOR ANY OF OUR 40+ FOAs. >> YEAH, AGAIN, THOSE ARE THE RIGHT KINDS OF QUESTIONS TO RAISE, IN SPECIFIC INSTANCES. OUR DEPUTY ETHICS COUNSELOR, DR. BAKER, WILL FIGURE OUT THE RIGHT WAY TO HANDLE, DISCLOSURE BEING THE FIRST, TRADITIONALLY IF YOU'RE AN APPLICANT INVOLVED IN A PARTICULAR FOA THEN YOU SHOULD HAVE NO INVOLVEMENT IN THAT FOA BECAUSE OBVIOUSLY IT'S RATHER DIRECTLY IMPORTANT BUT GOING OUTSIDE OF THAT I THINK WE'RE WANTING TO KNOW ABOUT IT BUT NOT EXPECTING THAT YOU WOULD PROBABLY BE EXCLUDED FROM CONSIDERING OTHER PARTS OF THIS VERY LARGE SPRAWLING HEAL INITIATIVE, OTHERWISE WE WOULD HAVE ALMOST NOBODY WHO IS KNOWLEDGEABLE ENOUGH TO ADVISE US. YEAH, ROB? >> WHILE WE'RE ON THE SUBJECT OF FOAs, IT'S BECOME KNOWN BY MY COLLEAGUES THAT I'M ON THIS GROUP, THERE'S BEEN A LOT OF QUESTIONS ABOUT FOAs TO I WITH I DON'T KNOW THE ANSWERS, ONE IS STATUS OF FOAs ISSUED AND ARE EXPIRED, OR EXPIRING. ARE THEY BEING REISSUED, OR WHAT I THE -- THERE WAS A SHORT LEAD TIME AND PEOPLE -- I JUST DIDN'T HAVE TIME TO RESPOND. SORRY, THAT'S A COMMON QUESTION THAT I'VE HEARD. >> AGAIN, IT'S A LITTLE BIT HARD TO SAY. UNEQUIVOCALLY ACROSS ALL OF HEAL . WE'RE STILL GETTING THE APPLICATIONS IN. WHAT WE'RE ANTICIPATING IS OBLIGATING ALL OF THOSE $850 MILLION, WE WOULDN'T BE RAMPING UP AND BRINGING IN NEW RESEARCH, THE NEXT FISCAL YEAR. HOWEVER, THERE MAY BE CASES WHERE THE BALANCE REQUIRES THAT WE RELEASE NEW ONES OR THAT TO SUSTAIN THE INVESTMENT WE MAIN WE'LL RELEASE NEW ONES, I WOULD ASK NORA AND WALTER AND THE OTHER INSTITUTE DIRECTORS PRESENT TO ADD TO THAT. >> IT'S GOING TO BE SOME OF THEM LIKE FOR THE MEDICATION DEVELOPMENT WHERE WE'RE ASKING EVERY THREE MONTHS THERE IS AN OPPORTUNITY FOR SUBMITTING PROPOSAL FOR THE CLINICAL TRIALS NETWORK, WE HAD A REQUEST FOR EXPANDING THE CTN, DEPENDING WHICH NOTES ARE SELECTED MAY NEED TO COME UP AND REQUEST AGAIN BUT WE'RE HOPEFUL WE'LL BE GETTING GOOD CASES. FOR THE HEALING COMMUNITIES, IT'S CURRENTLY BEING REVIEWED, THAT'S IN PRINCIPLE. SO VERY MUCH DEPENDS WHICH PARTICULAR INITIATIVE AND TYPE OF RESPONSES THAT WE GET. >> WOULD YOU SAY IT'S APPROPRIATE SINCE THE FOAs HAVE THE NAME OF A PERSON AT THE END OF THE FOA IF YOU HAD A SPECIFIC QUESTION ABOUT ONE OF THEM, ONE COULD POSE THE QUESTION YOU MIGHT NOT ENCOUNTER SOMEBODY WHO IS QUITE SURE OF THE ANSWER YET, BUT AT LEAST IT WOULD BE A BIT MORE THAN THIS VERY GENERAL RESPONSE WE'RE PROVIDING RIGHT NOW. >> THAT'S RIGHT. IT IS IMPORTANT TO INTERFACE WITH THE PROGRAM OFFICIALS, AND THE SCIENTIFIC STAFF, BECAUSE THIS IS NOT JUST A ONE TIME BOWL OF MONEY. THE BASE ON ONGOING BASIS CRAFTING PORTFOLIO, DOWN THE ROAD THERE WILL BE NEW OPPORTUNITIES, SO KEEPING THAT CONNECTION IS IMPORTANT. >> A QUICK QUESTION AS LONG AS WE'RE TALKING ABOUT THE FOAs, AND PEOPLE APPLYING. SOMEONE FOUND OUT I WAS ON THE COMMITTEE, THE FIRST THING THEY SAID WHAT DO YOU THINK THE PAYLINE WILL BE. [LAUGHTER] I SAID I HAVE NO IDEA. BUT A FAIR QUESTION, IF SOMEBODY IS DECIDING SHOULD I GO THROUGH THE TYPICAL R01 ROUTE OR SOME OTHER ROUTE VERSUS THROUGH HEAL , YOU OBVIOUSLY HAVE SOME SENSE, I WOULD IMAGINE, OF THE NUMBER OF APPLICATIONS THAT MIGHT COME IN AND GIVEN FUNDING, DO YOU HAVE ANY IDEA WHERE THAT MIGHT BE? IS IT COMPARABLE OR DOUBLE WHAT TYPICAL PAYLINE MIGHT BE? >> WE'RE STILL ACCEPTING APPLICATIONS FOR A LOT OF THESE AWARDS, SO WE HAVE -- WE CERTAINLY DON'T KNOW HOW MANY WE'VE GOT IN, WHAT THE PAYLINE IS GOING TO BE, HOW MERITORIOUS BUT I WOULD ENCOURAGE YOU TO TELL YOUR FRIENDS TO APPLY BECAUSE WE WILL FUND A LOT OF GRANTS THROUGH THEM. >> WE USUALLY DON'T FUND THINGS NOBODY SENT IN AN APPLICATION FOR. APPLY NOW, BY ALL MEANS. >> FAIR ENOUGH. >> I MIGHT JUST SAY THE -- CLINTON MENTIONED THIS, WE WILL PUT OUT THE FOA FOR THE CLINICAL SITES EPPIC-Net AGAIN BECAUSE WE DIDN'T GET ENOUGH SITES APPLYING. THAT'S ONE THING THAT -- AND THE OTHER THING REBECCA SAID THIS MONEY CAME TO THE BASE OF THE INSTITUTES, YOU KNOW, I MEAN WE'RE VERY OPTIMISTIC BUT WE'RE NOT GOING TO SOLVE THIS IN FIVE YEARS SO I THINK WE'RE GOING TO LEARN AND KEEP BUILDING UNTIL WE SOLVE THE PROBLEM SO I THINK THE OPPORTUNITY IS JUST ENORMOUS FOR US TO USE THESE FUNDS TO MAKE A DIFFERENCE AS FAST AS WE CAN, BUT THE MAIN THING IS WE MAKE A DIFFERENCE. >> FROM MY PERSPECTIVE FROM BACPAC, THIS IS NEW TO PUT SOMETHING TOGETHER ON THIS SCALE WITH THIS LEVEL OF INTEGRATION ACROSS DIFFERENT MODALITIES, NEW TO THE COMMUNITY AS WELL. SO ACTUALLY IT'S REALLY IMPORTANT FOR PEOPLE TO GET APPLICATIONS IN. WHAT WE MAY HAVE TO DO IS FOR SOME APPLICATION THAT ISN'T GREAT BUT HAS SOME COMPONENT LIKE ALGORITHM BUILDING, SOME CENTER HAS INFRASTRUCTURE FOR ALGORITHM DEVELOPMENT WE CAN GRAB THAT PIECE EVEN IF WE DON'T FUND THE WHOLE CENTER AS IT APPLIES. SO ACTUALLY WE ARE REALLY ENCOURAGING PEOPLE TO APPLY AND WE PROBABLY -- WE HAVE ONE OF OURS WHICH IS CLOSED WHICH WE MAY RE-OPEN SIMILARLY. BUT IF YOU HAVE SOMETHING GOOD, EVEN IF YOU CAN'T PUT THE WHOLE THING TOGETHER, AS LONG AS YOUR APPLICATION IS RESPONSIVE WE'RE GOING TO TRY TO LOOK AT ALL OF THEM TO FIND THE BEST PIECES BECAUSE WE'RE GOING TO NEED COMPONENTS THAT ARE NOT NORMALLY PART OF OUR PORTFOLIO. >> THANKS. THE ANSWER IS IT DEPENDS. >> IS REVISION POSSIBLE? >> SAY AGAIN. >> IN TERMS OF THE REVIEW PROCESS, BECAUSE IT'S SO FAST TURNAROUND, WILL THERE BE OPPORTUNITIES FOR REVISED PROPOSAL OR IS IT ONE SHOT? >> THAT DEPENDS TOO. AGAIN, THINK AS WITH EVERYTHING ELSE, THIS WILL GO THROUGH A SECOND ROUND OF REVIEW, AND IF THERE'S SOMETHING THAT LOOKS LIKE, WOW, THERE'S A HOLE HERE THAT COULD BE FILLED WITH AN APPLICATION BUT IT'S ONE THAT SEEMS TO HAVE A SIGNIFICANT FLAW THAT NEEDS TO BE REVISED, WELL, WE WOULD DO WHAT WE DO, WHICH IS TO ASK FOR A REVISED FORM OR GIVE SUGGESTIONS HOW BEST TO DO THAT. WE'LL TRY TO PLAY THIS AS FLEXIBLY AS WE CAN RECOGNIZING HOW IMPORTANT THE ISSUE IS. >> THAT'S GREAT. >> THANKS. WELL, YOU HAVE BEEN AT IT FOR ALL DAY. AND NO BREAK SINCE LUNCH. YOU'VE DONE FANTASTICALLY WELL BECAUSE WE'RE WELL AHEAD OF SCHEDULE WHICH IS ALWAYS A GOOD THING BECAUSE I'VE NOTICED IN MY TEN YEARS AS NIH DIRECTOR IT'S RARE THAT MEETINGS SUPPOSED TO ADJOURN AT 5:00 P.M. HAVE EVERYBODY STILL IN THE ROOM AT 5:00 P.M. THERE'S AIRPORTS AND TAXIS THAT GET IN THE WAY. ONE OF THE MY TRADITIONS IF I HAVE THE OPPORTUNITY TO BE PRESENT FOR THE ENTIRE MEETING WHICH DOES OCCASIONALLY HAPPEN, I'M GLAD IT DID THIS TIME, IS TO TRY TO THEN CAPTURE WHAT I HEARD FROM ALL OF THE PRESENTATIONS. IT'S A MEANS OF KEEPING MINUTES BUT ALSO MAYBE WILL BE A QUICK REFRESHER FOR YOU ABOUT WHETHER I AM ACCURATELY REFLECTING THE WISDOM YOU HAVE PUT ON THE TABLE. LET ME QUICKLY WALK THROUGH WHAT I HEARD PARTICULARLY ABOUT THE FIVE SPECIFIC PROJECTS THAT WE TALKED ABOUT. AND THEN I WANT TO ENGAGE YOU BRIEFLY IN SOME SENSE OF HOW THIS HAS BEEN FOR YOU, AS PART OF THIS NEW MULTI-DISCIPLINARY WORKING GROUP, A DIFFERENT MODEL, I'D LIKE TO HEAR HOW THIS WORKED IN TERMS OF INFORMATION YOU GOT, WHAT WAS MISSING, WHAT COULD HAVE BEEN HANDLED IN OTHER WAYS BECAUSE WE'RE GOING TO GET TO KNOW EACH OTHER WELL OVER THE COURSE OF THIS INTENSE YEAR. MAYBE BEFORE EVERYBODY SCOOTS WE WILL TRY TO TAKE A QUICK PHOTO BECAUSE THERE'S SOMEBODY WHO HAS A CAMERA IN HERE SOMEWHERE. SHE'S WAITING OUTSIDE. QUICKLY IN TERMS OF BY WAY OF SUMMARY OF TODAY'S DISCUSSION, YOU SURVIVED A NUMBER OF THE OPENING COMMENTS ABOUT THE COMPLEXITY OF THIS ENTERPRISE INCLUDING THIS DIAGRAM WHICH REPRESENTS 40+ DIFFERENT PROGRAMS, NOT ALL OF WHICH OF COURSE YOU HEARD ABOUT IN ANYTHING OTHER THAN SKETCHY FASHION AND SURVIVED GOVERNANCE OVERVIEW TO TELL WHERE YOU YOU FIT IN THE SCHEME OF THING IN THE PURPLE BOX AND HOW THIS ACTUALLY DOES MAKE SENSE ONCE YOU LOOKED AT IT, I HOPE YOU FEEL THAT WAY TRYING TO CAPTURE INPUTS WE NEED TO BE SURE WE'RE DOING THIS RIGHT. IN TERMS OF THE SPECIFIC FIVE PROJECTS WE HAD PRESENTED TO YOU FOR SPECIFIC DISCUSSION, LET ME QUICKLY SUMMARIZE WHAT I HEARD BUT THIS IS NOT ALL THE POINTS THAT ARE THERE, PLEASE DON'T BE OFFENDED IF I DIDN'T CAPTURE THE ONE YOU MADE. FIRST OF ALL THE FIRST PRESENTATION ABOUT OPTIMAL LENGTH FOR TREATMENT, FOR MEDICATION, FOR OPIOID USE DISORDER, YOU SAW THIS CREATIVE APPROACH ABOUT HOW TO DESIGN SUCH A STUDY IN A FASHION WHERE A PURELY RANDOMIZED APPROACH WAS JUDGED NOT TO BE PRACTICAL OR EVEN ETHICAL. AND SO TRYING TO ENHANCE RETENTION AND TREATMENT, ONE PART OF THE DESIGN, THE OTHER HOW TO SAFELY DISCONTINUE MEDICATION, THAT STRAW MODEL WHICH YOU SAW EVERYBODY SEEMED TO BE REASONABLY SUPPORTIVE BUT NOW IT'S GOT TO BE CONVERTED TO DETAILED PROTOCOL. THERE WAS AN INTERESTING SUGGESTION ABOUT CLUSTER RANDOMIZING WHEN YOU GET DOWN TO THE ARMS WHERE YOU'RE COMPARING STANDARD FOLLOW-UP VERSUS SOMETHING MORE INTENSE, ORDER OF RELAPSE PREVENTION, THERE MIGHT BE A REAL POTENTIAL THERE IN ORDER NOT TO HAVE THE WHOLE PROCESS CONTAMINATED BY PROFESSIONALS WHO PROBABLY BELIEVE THEIR SPECIAL INTERVENTIONS ARE SUPPOSED TO BE BETTER THAN STANDARD FOLLOW-UP. WE DO HOPE THERE WILL BE LOTS OF PEOPLE WHO CAN ALREADY GET INTO THE DISCONTINUATION PHASE SO WE DON'T HAVE TO WAIT TWO YEARS TO EVEN START THAT. I GUESS WE HEARD REASSURANCES THAT SOMEWHERE OUT THERE IN THE CPN THERE ARE THERE OUGHT TO BE ENOUGH OF THAT SORT. SO JUST A FEW OF THE COMMENTS RAISED AT THE END OF THAT PRESENTATION. THE BRIM WHICH WAS THIS ADDING BEHAVIORAL RESEARCH TO MEDICATION VERY IMPORTANT POINT MADE THAT NOT ONLY COULD THIS IMPROVE THE ABILITY FOR PEOPLE TO GET THROUGH OPIOID USE DISORDER TREATMENT BECAUSE IT HELPS WITH THE CRAVINGS AND OTHER ASPECTS OF OPIOID ADDICTION ITSELF BUT ALSO BECAUSE A LARGE ENHANCING PERCENTAGE OF THOSE PEOPLE HAVE PAIN THAT WILL STILL BE THERE, IF YOU DON'T WANT THEM TO STAY ON OPIOIDS THEY ARE GOING TO NEED SOMETHING TO BASICALLY KEEP THEM FROM SLIPPING BACK INTO RELAPSE AND BEHAVIORAL RESEARCH ENTITIES COULD BE A VERY IMPORTANT PART OF THIS. EVERYBODY FELT THIS WAS A REALLY IMPORTANT PART OF HEAL , TO INCLUDE THIS, STRONG SUPPORT FOR THAT. THE IMPORTANCE OF RETAINING NOT ONLY MEDICATION TREATMENT BUT IN BEHAVIORAL RESEARCH INTERVENTION WHICH MAY IN SOME INSTANCES BE DIFFICULT TO ACHIEVE BECAUSE OF DEMANDS ON PARTICIPANTS. QUESTION ABOUT WHETHER WE SHOULD INCLUDE NEW KINDS OF MIND-BODY INTERVENTION ON TOP OF WHAT IS BETTER TRAVELED TERRITORY WITH CBT AND MINDFULNESS, I DON'T THINK WE GOT A CLEAR ANSWER TO THAT BUT IT'S PROBABLY APPROPRIATE TO HAVE IT ON THE TABLE AS APPLICATIONS BEGIN TO BE ASSESSED. AGAIN, OVERARCHING GOAL HERE TO ENHANCE SELF CARE, AN IMPORTANT PERSPECTIVE TO FOLD INTO BRIM. GETTING INTO THE THREE PRESENTATIONS HOW WE'RE GOING TO DEVELOP, DISCOVERY, VALIDATE AND TEST PAIN TREATMENTS, PRE-CLINICAL RESEARCH VERY MUCH FOCUSING ON DISCOVERING NEW TARGETS AND VALIDATING THEM, BIG QUESTIONS ABOUT HOW DO YOU VALIDATE, ARE PAIN MODELS GOOD FOR CHRONIC PAIN AS OPPOSED TO ACUTE PAIN, DEPENDS ON TYPE OF CHRONIC PAIN, WE ARE ALL WONDERING CAN WE COME UP WITH BETTER MODELS FOR CENTRAL PAIN, WHAT IS IT ANYWAY? WHAT KIND OF MODELS WOULD FIT, COMBINATION OF CELLS, FISH, RATS, NON-HUMAN PRIMATES, NOT CLEAR IN ANY GIVEN INSTANCE WHAT THE RIGHT ANSWER IS. CLEAR EXHORTATION FROM ALL OF YOU THIS SHOULD BE MORE THAN JUST, OKAY, IS THE PAIN SOMEWHAT BETTER BUT ALSO WHAT IS THE LEVEL OF ACTIVITY AND FUNCTIONALITY OF THE INDIVIDUAL AFTER THAT KIND OF INTERVENTION HAS HAPPENED. AND WHAT CAN WE LEARN ABOUT THE WAY WHICH ANIMAL MODELS HAVE HELPED OR NOT HELPED FROM FAILED INDUSTRY PROJECTS IF WE COULD INDUCE SOME MORE SHARING IN THAT REGARD WHICH IS SOMETHING PERHAPS WE'LL HEAR MORE ABOUT TOMORROW IN THE HEAL PARTNERSHIP COMMITTEE. THE POTENTIAL ROLE OF CANNABINOIDS IN TERMS OF SERVING SOME POTENTIAL BENEFIT HERE STILL NOT AS WELL WORKED OUT AS WE ALL WISH IT WAS. AND LET'S BE SURE ALONG WITH THAT POTENTIAL COMPOUNDS THAT WE'RE PUTTING FORWARD AS ALTERNATIVES TO OPIATES ARE NOT JUST AS ADDICTIVE IF WE HAD ELEGANT WAYS TO BE SURE OF THAT. WE GOT TO EPPIC-Net, AND SORT OF AN INTERESTING DILEMMA HERE, WE WANT TO LOOK FOR EARLY WINS, AND, AGAIN, THE HPC TOMORROW WILL LOOK FOR EARLY WINS TO DESIGN THIS. COMPOUNDS READY FOR PHASE 2 THAT LOOK LIKE THEY ARE ON THE RIGHT PATH COULD BE VERY HIGH IN OUR PRIORITY IF THEY HAVE REASONABLE EVIDENCE THEY ARE GOING TO BE EFFECTIVE. BUT COULD WE CONSIDER COMPOUNDS FOR EPPIC-Net THAT STILL NEED PHASE 1 OR PARTS OF PHASE 1? IF SO MAYBE AS WAS POINTED OUT WE SHOULDN'T JUST DO A STRAIGHTFORWARD PHASE 1 BUT ADD MEASURES THAT MIGHT SHED LIGHT WHILE DOING THAT IN THE PHASE 1 PART. WHAT HAPPENS IF THERE ARE LOTS OF COMPOUNDS THAT LOOK PROMISING BUT STILL IN THE PRE-CLINICAL PHASE? DOES NOT SOUND LIKE EPPIC-Net IS SET UP TO DO A LOT OF THAT. DO WE HAVE OTHER THINGS TO STEP IN HERE, WE DON'T WANT TO MISS THOSE OPPORTUNITIES ESPECIALLY COMING FROM BIOTECH COMPANIES THAT MAY NOT HAVE THE RESOURCES TO DO THIS THEMSELVES BUT SITTING ON SOMETHING PRETTY GOOD. BLUEPRINT SEEMS TO HAVE SOME ASSETS HERE THAT COULD BE USEFUL. NCATS WAS VOLUNTEERED TO TAKE CARE OF SOME THINGS LIKE ADME TOX AND MORE THAN THAT. CLEARLY FOR EPPIC-Net TO BE SUCCESSFUL WILL NEED TO RAPIDLY ENROLL, HOW QUICKLY THAT CAN HAPPEN IS A FUNCTION OF THE TEN CLINICAL CENTERS AND HOW CONNECTED THEY ARE TO THE PAIN SUFFERERS OUT THERE IN THE COMMUNITY TO CONVINCE THEM THIS IS SOMETHING THEY WANT TO ENROLL IN. PRECISE PHENOTYPING BECAUSE OTHERWISE YOU DILUTE YOUR SIGNAL, AND WE'RE GOING TO HAVE TO BE CHALLENGED IN EVERY KIND OF PAIN PHENOTYPE TO KNOW HOW TO DO THAT. AND GENOTYPING WOULD BE NICE. I WAS ASKED TO COME UP WITH THE MONEY, NOT THAT MUCH SO LET'S THINK ABOUT WHAT IT WOULD TAKE. YOU CAN GET A SNP GENOTYPE THESE DAYS IF YOU DO IT AT SCALE FOR MAYBE $15 OR $20 PER PARTICIPANTS, A MODEST FRACTION OF THE TOTAL COST OF ANY OF THE TRIALS WE'RE TALKING ABOUT. I'M JUST SAYING. PARTNERSHIP WITH FDA, OBVIOUSLY CRUCIAL TO BE SURE WE DON'T END UP STUMBLING ON THOSE BE ON -- OBSTACLES. JANET WOODCOCK AND OTHERS AT FDA ARE MOTIVATED TO BE PARTNERS IN THIS SPACE AND MOVE THINGS ALONG. EVERY TIME WE ASK FDA FOR PARTICIPATION AND HELP THEY SAY YES AND THEY SAY YES QUICKLY. I DON'T THINK THIS IS GOING TO TAKE A BIG ARM TWIST BUT WE GOT TO BE SURE WE DO IT RIGHT. AND THIS THORNY QUESTION, WHAT ARE THE WAYS WHICH YOU'RE GOING TO ASSESS THE EPPIC-Net TRIALS, WHAT IS GOING TO BE THE PRIMARY OUTCOME, WHAT KIND OF BIOMARKERS, HAVE ANY VALID, DO WE GET STUCK WITH VAS OR SOMETHING MORE TO TRACK, A BIG DISCUSSION OF THE EPPIC-Net PROGRAM. FINALLY PAIN ERN, I HAD TO DO THIS WHILE WE WERE STILL HAVING A DISCUSSION SO I DIDN'T QUITE CAPTURE THE LAST BULLET ABOUT BIOSPECIMENS BUT THAT WAS A GOOD ONE TO ALSO PUT DOWN AS PROBABLY AN IMPORTANT THING TO AT LEAST COLLECT IF NOT PLAN TO SPEND A LOT OF MONEY ON DOING LAB TESTS QUITE YET. WE'LL BE CRITICAL, MDWG, TO GET BALANCE ONCE THROUGH REVIEW, THAT FIVE OR SIX YEARS TO GET RESULTS I THINK CAUSED SOME PEOPLE TO HAVE A SUDDEN INTAKE OF BREATH SO THE MORE WE CAN COME UP WITH ACCELERATED WAYS WITHOUT COMPROMISING THE RIGOR OF THE DATASET, AND ALSO WAYS TO LEARN ALONG THE WAY WITH METADATA AND THE TRIALS THAT I THINK WOULD HAVE SOME INSTANCES WHERE THAT COULD BE DONE WOULD BE A REALLY GOOD THING. AND THE LAST SLIDE IS GENERAL ISSUES THAT WEREN'T ATTACHED TO THE FIVE SPECIFIC PROJECTS, BUT I THINK POINTS WERE MADE, MANY MADE IN THE COURSE OF DISCUSSION THIS MORNING AFTER THE REALLY REMARKABLE PRESENTATIONS FROM JESSICA AND CHRISTIN AND A FEW OTHERS KEEPING HEALTH EQUITY ISSUES IN MIND IN ALL PROJECTS, THAT'S NOT THE AFTERTHOUGHT. REIMBURSEMENT, EVIDENCE TO CONVINCE CMS, ANYTHING NEEDS TO BE THOUGHT OF, WILL IT BE ENOUGH FOR SEEMA VERMA TO SAY WE'RE GOING TO PAY FOR THIS. WORKFORCE TRAINING, WE'RE WAY SHORT ON EXPERTISE IN TERMS OF RESEARCH AND PRACTICE. THE IDEA THAT OPIOID USE DISORDER JUST NEEDS TREATMENT AND EVERYTHING IS FINE IS WAY TOO SIMPLISTIC, SUPPORT FOR RECOVERY PROGRAMS, ONGOING PROGRAMS, NEEDS ALSO TO BE FACTORED IN HERE. DATA SHARING CAME UP NUMEROUS TIMES, WELL IT SHOULD, AND I WANT TO PROMISE YOU WE WILL WATCH THAT CLOSELY AND WITHIN THE LIMITS THAT WE CAN DO SO WE'LL BE PUSHING APPLICANT INVESTIGATORS TO GO BEYOND THE USUAL TRADITIONS BEING BURIED WITH YOUR DATA, IT'S NOT WHAT WE HAD IN MIND. THIS IS REALLY SOMETHING WHERE WE HAVE TO LEARN AS MUCH AS WE CAN AS SOON AS WE CAN. I THINK WE NEED TO CONSTANTLY, WE DID IT TODAY, KEEP UP AND AVOID TENDENCY FOR THIS TO BE TWO DISCONNECTED COMPONENTS ON HEAL, ONE ON OPIOID ADDICTION, ONE ON FINDING ALTERNATIVES FOR CHRONIC PAIN. THEY ARE CONNECTED. WE SAW WAYS THAT WAS THE CASE. BUT WE HAVE SOMEWHAT SEPARATE TEAMS AND SEPARATE FOAs, IT'S UP TO US, I'M TALKING TO MYSELF AS WELL AS ALL OF YOU, TO KEEP LOOKING FOR THOSE AREAS OF OVERLAP. AND THEN DIANA RAISED THIS ISSUE ALL OF THESE ISSUES ABOUT SEX AS A BIOLOGICAL VARIABLE, CERTAINLY IN CLINICAL TRIALS WE'RE PRETTY USED TO NOW THINKING ABOUT THAT, WE SHOULD BE, BUT ALSO ANIMAL STUDIES AND EVEN IN CELLS THIS TURNS OUT TO BE A HUGE ISSUE. IF YOU DON'T DESIGN YOUR ANALYSES TO LOOK FOR THAT THEN YOU WON'T FIND IT. YOU WOULDN'T WANT TO MAKE THAT MISTAKE. THAT WAS MY SUMMARY OTHER THAN TO SAY THANK YOU FOR A REALLY GREAT MEETING. THIS IS INCREDIBLY VALUABLE DISCUSSION FOR ME AND I THINK I'M SPEAKING FOR ALL THE INSTITUTE DIRECTORS HERE GETTING YOUR INPUT. AGAIN I THINK THIS WAS A SOMEWHAT GENTLE VERSION OF WHAT'S GOING TO BE HAPPENING LATER IN THE YEAR WITH MORE DECISIONS AND MORE INTENSITY BUT IT WAS CERTAINLY GREAT FOR ME AS SORT OF FIGURING OUT HOW WE'RE GOING TO MOVE THIS FORWARD TO SEE IT TAKE SHAPE IN THE CONTEXT OF THIS CONVERSATION AND HEAR ADVICE FROM YOU, THE KIND OF GROUP I THINK WE'RE GOING TO NEED GOING FORWARD. I FEEL ENCOURAGED. WITH THAT LET ME ASK YOU FOR YOUR PERSPECTIVE, MEMBERS, ABOUT HOW THIS IS TAKING SHAPE, THINGS THAT YOU'RE WORRIED ABOUT, THINGS YOU'RE EXCITED ABOUT, ANYTHING YOU WANT TO SAY TO ME, TO REBECCA BAKER, NORA VOLKOW, WALTER KOROSHETZ, OTHER DIRECTORS HERE ABOUT WHAT WE'VE ASKED YOU TO DO THAT WOULD HELP US MAKE THIS INTO A SUCCESSFUL ALBEIT SOMEWHAT CRAZY YEAR. WALLY? >> THE NIH PAIN CONSORTIUM HAS BEEN AROUND FOR QUITE SOME TIME. BUT A WAY OF CONTINUING THIS DIALOGUE BETWEEN THE OPIOID USE DISORDER TEAMS AND THE PAIN TREATMENT AND DISORDER TEAMS IS TO THINK ABOUT CONSORTIUM OF SOME SORT OF STANDING CONSORTIUM WITH NIH THAT HEAL WOULD OVERSEE OR SPONSOR TO CONTINUE THE DIALOGUE SO NOT JUST THE WORKING GROUP IS ADVISING BUT THE CONSORTIUM IS SHARING INFORMATION AS IT COMES AVAILABLE. THE CONSORTIUM MEETS ONCE A YEAR RIGHT NOW, IT'S A PRETTY GOOD SCIENTIFIC MEETING. I'M NOT SURE THERE'S A MEETING LIKE THAT WHERE OPIOID USE DISORDER FOLKS, PAIN FOLKS ARE TALKING TO ONE ANOTHER. >> UH-HUH. >> GOOD POINT. THE PAIN CONSORTIUM, WE HAVE THIS SYMPOSIUM ONCE A YEAR, THAT'S ACTUALLY, YOU'RE RIGHT, THERE WILL BE A LOT MORE ACTIVITY WE COULD LEVERAGE THERE. WE ALSO HAVE THE PAIN CONSORTIUM WITHIN NIH, TRYING TO FIGURE OUT HOW TO INCORPORATE THE HEAL FOCUS AND INCLUDE ALL THE PAIN CONSORTIUM MEMBERS SO WE HAVE THE ABILITY TO REACH OUT ACROSS ALL THE ICs SO I THINK THIS IS GOING TO STRENGTHEN THAT PAIN CONSORTIUM IN GENERAL. THE PAIN CONSORTIUM, NORA IS THE MAIN -- SHE'S THE MAIN -- ONE OF THE MAIN CONTRIBUTORS SO I THINK WE DID HAVE A GROUP. MAYBE AWAY HAVE RENAME IT, NORA. >> THAT'S PROBABLY THE MOST EFFICIENT WAY OF DOING IT BECAUSE IN THE PAIN CONSORTIUM WE HAVE THE EXPERTISE OF THE INSTITUTES THAT ARE DEALING WITH BOTH SIDES OF THE OPIOID USE DISORDERS AND PAIN. CONSIDERING WITH BEING SENSITIVE TO THE FACT OVERALL MANY TIMES THERE'S PERCEPTION WE HAVEN'T PAID SUFFICIENT TO PAIN, BUT IF WE CAN COME UP WITH A NAME. THE OTHER THING BY THE NATURE OF WHAT WE DID TODAY I THINK THAT THERE IS EXACTLY THE OPPORTUNITY OF CREATING THESE BRIDGES ACROSS BOTH OF THESE FIELDS, IN A WAY THEY ARE MORE INTEGRATED AND IF YOU LOOK AT THE PLAN FOR THE GOVERNANCE OF THE HEAL YOU ARE THE PURPLE, AND THEN WE HAVE THE YELLOW BARS WHICH THE OTHER AGENCIES, ADDICTION AND PAIN, AND BELOW THEM ARE A LOT OF OUR PROGRAM OFFICERS AT INSTITUTES THAT ARE GOING TO BE WORKING TOGETHER WITH A LOT OF THINGS HAPPEN SO WE HAVE A STRUCTURE THAT IS QUITE SOLID THAT IF IT DOES NOT LOOK LIKE WE'RE BEING ABLE TO SUCCEED IN BRINGING THEM TOGETHER SHOULD RECONSIDER IT. WE'VE BEEN THINKING, WE, IT'S REBECCA WHO HAS DONE A LOT OF THE THINKING TO COME WITH A PROCESS THAT WILL INTEGRATE SUCH A DIVERSE GROUP OF INDIVIDUALS, SPEAKING ABOUT PAIN AND OPIATE USE DISORDERS, PHARMACOLOGY, PRIVATE INDUSTRY, DEVICES, THAT DIVERSITY BECOMES A BIG CHALLENGE. >> WHAT ABOUT THE ANNUAL MEETING, WALTER? YOU ALREADY HAVE THIS FOR THE PAIN CONSORTIUM. CAN THIS ABSORB THIS INCREDIBLE ACTIVITY THAT'S NOW GOING TO BE INSPIRED BY THE HEAL INITIATIVE OR DO WE NEED TO THINK ABOUT ADDITIONAL GATHERINGS TO SHOWCASE THE WORK THAT'S BEING DONE? >> I THINK WALTER'S POINT WAS MAYBE WE NEED TO ADD SOME ADDITIONAL MEETINGS WHERE SIMILAR TO THE PAIN CONSORTIUM MEETING WE COULD INCORPORATE DIFFERENT ASPECTS OF HEAL AND I THINK THAT'S YOUR POINT. I WOULD AGREE WITH THAT, YEAH. >> I THINK AS WE START MAKING THESE AWARDS TOO WE'LL HAVE A GRANTEE COMMUNITY THAT WE'LL WANT TO BRING TOGETHER, THAT WILL BE THE APPROPRIATE VENUE. >> YEP. >> A QUESTION PLEASE. I DON'T KNOW IF THIS CAME EARLIER, I READ IN THE "NEW YORK TIMES" A COUPLE DAYS AGO, I DON'T KNOW WHAT PART OF GOVERNMENT IS PLANNING TO DO THIS, THERE'S A BIG DISCUSSION ABOUT GETTING TO THE QUESTION OF THE USE OF OPIOIDS FOR CHRONIC NON-CANCER PAIN, AND PEOPLE IN THE FIELD, IT'S NOT EFFECTIVE, I KNOW PEOPLE IN THE FIELD WHO THINK IT'S VERY EFFECTIVE, AMONG THE MOST CONTROVERSIAL AREAS, THINGS LIKE BACK PAIN, OA, ET CETERA. MY UNDERSTANDING IS THERE'S SOME PUSH IN SOME GOVERNMENT AGENCY, I DON'T THINK IF IT'S RELATED TO HEAL AT ALL, TO ACTUALLY DO STUDIES DIRECTING LITERALLY TO GET AT THE QUESTION OF EFFICACY, IS THAT SOMETHING THAT'S UNDER THE HEAL INITIATIVE OR INDEPENDENT OF IT? >> THIS IS REBECCA. MY UNDERSTANDING THAT CAME THROUGH THE SUPPORT ACT, AND IT WAS FOR FDA TO TACKLE BECAUSE WE DO HAVE THESE GOOD RELATIONSHIPS, I'M SURE WE'LL BE IN TOUCH WITH THEM AS THEY TAKE ON THAT PROJECT, BUT STRICTLY SPEAKING IT'S NOT PART OF HEAL . >> IT SEEMS LIKE IT SHOULD BE. >> SOME COMPARISONS -- WHERE IS JANE? SOME OF THE -- IN THE PRISM STUDY, MAYBE MORE COMPARATIVE EFFECTIVENESS, THAT THE UTILITY OF OPIOIDS VERSUS NON-OPIOIDS OR OPIOID SPARING THAT WILL COME UP AS POTENTIAL QUESTIONS TO BE ADDRESSED BY THAT RESEARCH. >> YOU KNOW, JUST TO AARON KREBS DID THE SPACE STUDY FAIRLY RECENTLY, NICELY DONE. WHICH IS LOOKING AT THAT. >> (INAUDIBLE). >> TURN YOUR MIC ON. >> THE SPACE STUDY WAS LOW BACK PAIN, OSTEOARTHRITIS OF THE KNEE I THINK, A COUPLE OTHER CONDITIONS, MULTI-CONDITIONS. AND IT WAS ONE YEAR. OPIOID VERSUS NON-OPIOID THERAPY. AND THE RESULTS CAME OUT IN JAMA. >> YES. >> AND SHOWED NO DIFFERENCE IN EFFICACY, AND SHOWED HARMS WITH REGARD TO SIDE EFFECTS FOR OPIOIDS. >> YES. YEAH, THAT WAS PRETTY COMPELLING. >> THAT WAS THE FIRST, I THINK, EVER STUDY OF OPIOIDS BEYOND 12 WEEKS, CHRONIC OPIOID THERAPY BEYOND 12 WEEKS FOR ANY CONDITION, RANDOMIZED CONTROL TRIAL. A BIG DEAL. >> HEATHER? >> I WAS THINKING ABOUT DISSEMINATION EFFORTS, YOU'RE LAUNCHING THIS NOW, I'M THINKING FAR DOWNSTREAM BUT I THINK YOU NEED TO THINK ABOUT THE INFRASTRUCTURE FOR IT NOW SO THAT YOU'RE READY. BECAUSE WE HAVE THAT 14-YEAR LAG IN GETTING RESEARCH TO PRACTICE, HOW WE SHORTEN THAT RUNWAY AND THINKING ABOUT MAPPING ALL OF THE AREAS THAT WE ALREADY HAVE, WITH LIKE ACOG AND CPDD AND THE PAIN MEETINGS, A LOT OF EFFORTS THERE, AND THINKING ABOUT SAMHSA AND THINKING ABOUT PLACES LIKE NASA DAD, LIKE UNIVERSITIES, IS THERE SOME KIND OF ALREADY INFRASTRUCTURE WORKING GROUP THAT CAN REALLY TRULY THINK ABOUT WHAT IS THE RUNWAY FOR DISSEMINATION EFFORTS? EACH OF THE INSTITUTES HAVE PUBLIC MEDIA FOLKS, HOW CAN YOU UNIFY LEVERAGE THAT SHOULD REALLY MAKE THE SEAMLESS RUNWAY BECAUSE IF YOU CAN DO THAT NOW THEN YOU'VE GOT THIS WHOLE MECHANISM NOT JUST FOR THE NEXT FIVE YEARS BUT A LONG TIME. >> YEAH, THAT'S A GOOD POINT. AGAIN, THAT YELLOW BOX OF FEDERAL PARTNERS IS CRITICAL FOR TRYING TO GET THAT IN TRAIN WITH LIKE FDA AND PARTICULARLY CDC, CMS. BUT I THINK IT'S PROBABLY A GOOD TOPIC FOR THE EXECUTIVE COMMITTEE OF NIH INSTITUTE DIRECTORS TO THINK, GOOD POINT. >> IT'S ONE OF THE ADVANTAGES THAT I THINK WE'VE LEARNED WITH CLINICAL TRIAL NETWORK OF USING MULTI-SITES, MUCH MORE OF A CHANCE THAT PEOPLE ADOPT THINGS STUDIED, AND ONCE MANY PLACES ARE ADOPTING THEM, ANYWAY, JUST ONE. THE QUESTION I HAD WAS JUST A LITTLE BIT OF A CLARIFICATION WHICH I PROBABLY SHOULDN'T NEED BY NOW, BUT IN TERMS OF ADDICTION AND OPIOID USE DISORDERS, ARE WE REALLY FOCUSING PRIMARILY ON THOSE THAT ARE CAUSED BY PAIN? ARE WE -- YOU KNOW, I MEAN I'M JUST WONDERING, I DON'T THINK WE ARE, I DON'T THINK THAT'S THE ANSWER BUT KIND OF THE FOCUS TODAY. >> THE REASON THINGS LIKE THAT, THAT'S HOW THE OPIATE CRISIS STARTED BUT TRANSFORMED ITSELF. HEAL IS END ADDICTION LONG-TERM SO EVENING THOUGH WE'RE ADDRESSING OPIOIDS IT DOES RECOGNIZE SOME ADVANCES WILL BE BENEFICIAL IN ADDRESSING ADDICTION BECAUSE WE'RE SEEING MORTALITY GOING UP FOR COCAINE AND METHAMPHETAMINE. SO NO, IT'S NOT JUST LIMITED FOR THE PAIN. IT SO HAPPENS THAT IN THE PROCESS OF ADDICTION AND YOUR WORK HAS BEEN ONE OF THE FIRST ONES TO DOCUMENT THAT, THAT YOU HAVE A MUCH HIGHER PREVALENCE OF PAIN IN PATIENTS SUFFERING FROM ADDICTION THAN IN THE GENERAL POPULATION, AND YET WE DO NOT PER SE DEAL WITH IT AS THE MORBIDITY, LIKE COMORBIDITY OF MENTAL ILLNESS, HOW DO WE TACK AM IT, WE NEED TO TACKLE IN AN INTEGRATED FASHION. BUT, NO, IT'S NOT JUST -- >> NO, GOOD TO HAVE THAT CLARIFIED. RICK? >> A HOUSE KEEPING ISSUE. THE CTSA REQUIREMENT FOR C DASH AND CDISC IS FANTASTIC. CAN WE REQUIRE APPLICANTS TO USE THOSE SO DATA CAN BE SHAREABLE AND PROVIDE A CDISC PLAY BOOK, IF YOU THOUGHT ABOUT REQUIREMENTS FOR APPLICATIONS TO USE THOSE STANDARDS. >> I ASSUME PAIN ERN WILL, RIGHT? WHAT ABOUT -- YES? >> THE WAY WE WENT ABOUT THAT WE THOUGHT ABOUT IT A LOT, BUT DECIDED NOT TO -- THERE WAS A PUBLICATION MAYBE A YEAR OR TWO AGO THAT CAME OUT OF THE PAIN CONSORTIUM, A SET OF WHAT YOU SHOULD REPORT IN BACK PAIN STUDIES AS COMMON -- COMMON REPORTED ITEMS. BUT EVEN THERE THERE'S ALWAYS SOME PEOPLE WHO PUSH BACK AND SAY NO, THAT'S NOT QUITE RIGHT. WHAT WE DECIDED IS IN A FIRST MEETING ONCE THE BACK PAIN CONSORTIUM IS SET UP THE INVESTIGATORS WILL MAKE THOSE DEFINITIONS, DEFINE LOW BACK PAIN TO START WITH, DEFINE THE COMMON DATA ELEMENTS, DEFINE OUTCOME MEASURES USED ACROSS THE NETWORK. OUR APPROACH WASN'T TO PRE-SPECIFY IN THE FOA BUT TO& HAVE THAT IN THE FOA AS A FIRST TASK FOR THE INVESTIGATOR ONCE THE CONSORTIUM IS FORMED. >> MAYBE WE COULD LOOK AT THE NON-PAIN ELEMENTS AND MAKE SURE THEY ARE STANDARDIZED, BECAUSE THE PROBLEM WITH COMBINING DATA, METANALYSIS, INDIVIDUAL PATIENT LEVEL, IS THAT WHEN THE STANDARDS ARE DIFFERENT IT'S ALMOST IMPOSSIBLE TO COMBINE THE DATA TO GET POWER. SO JUST A SUGGESTION. >> I THINK LINDA IS NOT HERE BUT SHE'S WORKED-- LINDA PORTER RUNS THE PAIN POLICY AND PLANNING, IS TRYING TO GET THE GROUPS TOGETHER TO DEVELOP COMMON DATA EEMENTS THAT COULD BE USED ACROSS HEAL . NOW THE CDISC PART, YOU IMAGINE THERE ARE CDISC ELEMENTS FOR DIFFERENT PAIN SYNDROMES, YEAH, OKAY. THAT WOULD BE GOOD TO INCORPORATE. I WAS GOING TO ASK PATRICE IN TERMS OF HENDREƒ'S QUESTION ABOUT DISSEMINATION, CAN YOU GIVE ADVICE ON HOW WE SHOULD THINK AT LEAST IN TERMS OF DISSEMINATING INFORMATION TO THE PHYSICIANS. >> FIRST OF ALL, THAT'S A GREAT SUGGESTION. IT'S GOOD TO KEEP THAT IN MIND AT THE BEGINNING. WE'RE HAPPY TO HELP YOU THINK THROUGH THAT MORE AND MAKE SURE WE CAN HELP DEVELOP WAYS TO GET IT THROUGH BUT CERTAINLY SPECIALTY SOCIETY MEETINGS ARE GREAT AT THE STATE AND LOCAL LEVELS, FOR THOSE WHO DON'T KNOW WE HAVE A MICROSITE, OPIOID TASK FORCE HAS A MICROSITE ON AMA WEBSITE, AND WE ARE ALWAYS WILLING TO HAVE ADDITIONAL RESOURCES ON THAT WHERE PHYSICIANS CAN GO TO EITHER STATE SPECIFIC INFORMATION OR SPECIALTY SPECIFIC INFORMATION OR GENERAL INFORMATION SO WE WOULD BE HAPPY TO HAVE INFORMATION ON THAT SITE, FOLKS CAN GET ACCESS THERE AND WE'LL BE HAPPY TO BRING THIS UP AT OUR NEXT TASK FORCE MEETING AND THINK THROUGH AND I WANTED TO SAY EARLIER IN ADDITION TO THE AMA OPIOID TASK FORCE WE HAVE CONVENED A PAIN TASK FORCE, AND NOW WE'RE THINKING AHEAD, AT SOME POINT IN THE FUTURE WE'LL PROBABLY COMBINE THE TWO TASK FORCES AS WE'VE BEEN CHATTING ABOUT THE -- HOW THOSE TWO ISSUES ARE SO INTERWOVEN BUT WE WOULD BE HAPPY, AGAIN, TO USE THOSE VEHICLES TO GET THE INFORMATION OUT AS WELL. >> THAT WOULD BE GREAT. I THINK WE HAVE, SPEAKING FOR THE OTHER IC DIRECTORS, PRETTY GOOD TIES TO SUBSPECIALTY GROUPS BUT NOT WITH THE PRIMARY CARE PHYSICIANS WHO ARE THE MAJOR PLAYERS IN THE SPACE, SO WE REALLY NEED HELP THERE. >> SO WE TALKED ABOUT PAIN, WE TALKED ABOUT MENTAL HEALTH BUT HAVEN'T TALKED SO MUCH ABOUT SOCIETAL OR COMMUNITY-RELATED ISSUES THAT EITHER CONTRIBUTE TO THE CRISIS OR AREAS WHERE THERE'S RESILIENCE, AND I'M JUST WONDERING IS THIS SOMETHING OBSSR IS GOING TO TACKLE? WHERE DOES THIS FIT IN THE BIG PICTURE? >> THAT RELATES TO SOCIOECONOMIC ASPECT OF DISEASE, YEAH, BUT IT'S ALSO -- IT HAS A SHORT AND LONG TERM, SHORT TERM STRUCTURE OF RESOURCES AND LONG TERM OF COURSE RELATES TO ALL OF THE RISK AND VULNERABILITY. AND THIS IS AGAIN IN MANY WAYS MUCH HARDER TO ADDRESS BUT BEHOOVES US TO DO IT. THE PROJECT WOULD BE A LONG-TERM PROJECT, THE BCD PROJECT WHERE WE'RE GOING TO BE ABLE TO MONITOR INDIVIDUAL BRAIN TRAJECTORIES OF CHILDREN THAT WILL BE DEEPLY PHENOTYPED FROM ENVIRONMENT, SOCIAL FACTORS, PARENT FACTORS, GAIN KNOWLEDGE HOW ENVIRONMENT INFLUENCE THE BRAIN AND HOW THAT INFLUENCES YOUR BEHAVIOR AND HOW THAT INFLUENCES OTHER DISEASES. IT'S VERY AMBITIOUS. FROM THE HEAL PROJECT WHERE I SEE AN OPPORTUNITY, ONE OF THE AREAS WE HAVEN'T DISCUSSED HERE IS ANYTIME WE GET MONEY FROM CONGRESS THERE'S A CERTAIN PORTION THAT HAS TO GO FOR SBIR AND STTRs, THAT'S TO HELP SMALL BUSINESSES TO COME UP WITH PRODUCTS THAT CAN MAKE THE MONEY BUT VERY IMPORTANTLY ADDRESS QUESTIONS. AND THERE IS SBIR/STTR FOR HEAL , ONE AREA WE'RE HAVE HAD IS TO REQUEST PROPOSALS ABLE TO TACKLE SOME OF THE SOCIOECONOMICAL ASPECTS THAT WERE HINTED AT, FOR EXAMPLE HOW DO YOU PROVIDE, HOW DID YOU EXPAND ACCESS TO PLACES PEOPLE CAN STAY IF THEY ARE HOMELESS TO STRAIN TREATMENT, ASPECTS WE HAVEN'T ENGAGED IN THE PAST BUT THE CRISIS IN THE WAY FORCED TO THINK, OFFERING AN OPPORTUNITY TO USE THOSE RESOURCES IN WAYS TO ADVANCE IT. >> I WAS THINKING ABOUT LIKE JUST READING DREAMLAND RIGHT NOW SO IT'S VERY MUCH ON MY MIND, BUT COMMUNITY CHANGES THAT PROFOUNDLY AFFECT THE WAY PEOPLE INTERACT, AND THEN MAY PREDISPOSE TO ADDICTION. >> AGAIN, IMMEDIATE AND LONG TERM, ONE OF THE VERY EXCITING ASPECTS OF THE HEALING COMMUNITY IT AIMS -- THE COMMUNITIES WORK TOGETHER AND THEY ACTUALLY IDENTIFY WHAT THE PLAN OF ACTION IS GOING TO BE. THE IDEA IS THAT KNOWLEDGE THEN COULD BECOME AVAILABLE FOR OTHERS TO TAKE. ABSOLUTELY. THAT IS ONE OF ITS MAIN PURPOSES, THE COMMUNITIES WORK WITHIN THEIR OWN COMMUNITY RESOURCES BUT ALSO WITH EDUCATION DEPARTMENT, WITH, AS I MENTIONED, HEALTH AND JUSTICE SYSTEM, BEHAVIORAL HEALTH, SO HEALING COMMUNITIES WILL BE A PERFECT COMMUNITY TO DO IT. >> ONE MINOR POINT, I THINK OBSSR, OFFICE OF BEHAVIORAL AND SOCIAL SCIENCE RESEARCH AT NIH, SIGNED ON TO A LOT OF THE HEAL FOAs, SO THEY HAVE, YOU KNOW, AT THIS ENTRY LEVEL INDICATED THEIR INTEREST IN PARTICIPATION, AND FROM THE NIH INTERNAL SIDE IT'S UP TO US TO MAKE SURE THAT WE AS WE MOVE FORWARD WITH SCIENTIFIC TEAMS MEANINGFULLY INTEGRATE THOSE CONCEPTS INTO THE AWARDS WE MAKE AND THE PLANS FOR THOSE STUDIES. >> SO ONE OF THE THINGS I'VE REALIZED, FROM THE DENTAL OF THIS, WE TALK ABOUT AMA, ADA, NIDA, NIDCR PUTTING ON A CEP NON-PHARMACOTHERAPY -- PUTTING ON A WEBINAR, IT'S AN AREA, SO AS WE'RE WORKING TODAY, AND I ENJOYED THE INTERACTIONS HERE, BUT WHEN YOU TALK ABOUT INSURANCE COMPANIES DON'T FORGET THE DENTAL SIDE OF IT AND ALSO I THINK ONE OF THE THINGS THAT WE NEED TO DO IS GET BACK TO THE SCHOOLS AND TO THE STUDENTS AND THAT REALLY IS AN IMPORTANT PART OF THE COMMUNICATION AS WELL THAT WE'RE TRYING TO DO FOR DENTAL BUT NEED TO DO IT IN MEDICINE, NURSING, EVERYTHING. >> (INAUDIBLE). >> I THINK IT'S BEEN A GREAT DAY. I'M EXCITED ABOUT THE WORK. I'M WORRIED HOW WE'LL DO IT BUT REBECCA WILL FILL US IN, IN A MINUTE. WE HAVE A MAY DATE BUT MAYBE AN AUGUST DATE TOO. ONE THING I'M CONCERNED ABOUT IS ESPECIALLY AFTER JANE'S PRESENTATION IS ONCE THE GRANT MONEY DRIES UP, P.I. IS NO LONGER BREATHING DOWN THE CLINICIAN'S NECK, COLLECT THESE DATA IN STANDARDIZED WAY, HOW IS PRACTICE SUSTAINED? I DIDN'T HEAR ANYTHING ABOUT SUSTAINABILITY, AGAIN IMPLEMENTATION SCIENCE SIDE OF IT AND WHO AT THE TABLE HAS EXPERTISE, SO THAT CLINICAL SITES CAN BE SUCCESSFUL. SO, I DON'T KNOW IF ANYONE HAS A THOUGHT. WE BROUGHT IT UP SEVERAL TIMES TODAY. I THINK THAT IF WE DON'T ADDRESS SUSTAINABILITY ASPECT NO MATTER HOW MUCH MONEY WE THROW WE HAVE TO SUSTAIN THE CLINICIAN'S BEHAVIOR TO SUSTAIN THE PATIENT'S CHOICES AND BEHAVIOR AS WELL. >> SOME OF THE PRISM CLINICAL IMPLEMENTATION TRIALS IN REAL WORLD CLINICAL PRACTICE WILL ADDRESS SOME OF THAT. I DON'T KNOW ABOUT YOU'RE TALKING ABOUT SUSTAINING OVER A LONG TIME BUT IT WILL BE HOW DOES THIS WORK IN A CLINICAL PRACTICE, THAT'S WHAT THOSE STUDIES, WE DIDN'T TALK ABOUT THEM BUT YOU'LL HEAR TODAY. >> ISN'T IT THE CASE WITH THE NIH DoD VA PAIN COLLABORATORY TRIALS THERE'S MORE MONEY TO LOOK AT THAT IN A SYSTEMATIC WAY? >> YES. >> GOOD EXAMPLE. WE WERE FORTUNATE CONGRESS GAVE THIS HALF A BILLION DOLLARS TO NIH IN THE BASE, SO IF WE NEED TO CONTINUE BEYOND THIS CURRENTLY OUTLINED SET OF PROGRAMS TO DO NEW IMPORTANT THINGS INCLUDING IMELEMENTATION RESEARCH WE SHOULD BE ABLE TO HAVE THE RESOURCES TO DO THAT. >> YES, ROB? >> GIVEN MEETINGS ABOUT PUBLIC/PRIVATE PARTNERSHIPS, HOW THAT WAS A BIG PART OF WHAT WE'RE DOING, I WAS SURPRISED TO HEAR ABOUT THE WAY THAT'S BEING ROLLED OUT. I'M CURIOUS TO KNOW WHERE THE PARTNERSHIP PART IS BECAUSE IT SOUNDS LIKE WE'RE SETTING UP A BIG INFRASTRUCTURE, A LOT OF PUBLIC INVESTMENT BASICALLY GOING TO CONDUCT A CLINICAL TRIAL FOR AN ASSET THAT'S ALREADY BEEN DEEMED SAFE AND SO FORTH SO SOUNDS LIKE PUBLIC INVESTMENT BASICALLY IN PRIVATE COMPANIES. SO WHERE IS THE PARTNERSHIP PART? A COROLLARY, THERE SHOULD BE INSISTENCE ON INFORMATION IN THE OTHER DIRECTION REGARDING CLINICAL TRIAL FAILURES AND PRE-CLINICAL PACKAGE THAT GOES WITH IT. MAYBE THIS IS A PROMPT FOR DISCUSSION TOMORROW, WHICH I WILL NOT BE PART OF, SHOULD THAT BE A MANDATED PART OF THAT PARTNERSHIP? >> I THINK THAT'S A VERY APPROPRIATE POINT THINKING HOW TOMORROW IS GOING TO GO. THE HEAL PARTNERSHIP COMMUNITY HAS REPRESENTATION IN THE SPACE. I THINK INDUSTRY IS EXPRESSING CONSIDERABLE WILLINGNESS TO OPEN U ABOUT LOTS OF THINGS THAT NORMALLY THEY WOULD NOT. INCLUDING CONTRIBUTION OF INFORMATION AT SOME LEVEL OF DETAIL ABOUT THESE POTENTIAL ASSETS THAT MIGHT ULTIMATELY TURN OUT TO BE REALLY IMPORTANT FOR TREATMENT OF PAIN. IT IS A LITTLE TOUGHER WHEN IT COMES TO OPENING UP INFORMATION ABOUT FAILED PROJECTS. I THINK THERE IS WILLINGNESS ON THE PART OF QUITE A FEW OF THE INDUSTRY PARTICIPANTS TO DO SO. I'M NOT SURE IT'S UNIVERSAL BUT BELIEVE ME WE'LL BE PUSHING HARD ON THAT. AGAIN AS I SAID AT THE BEGINNING INITIALLY THE IDEA WE WOULD HAVE A SHARED COST MODEL HERE WHERE INDUSTRY WOULD COVER SOME COST. THE SENSE WAS OF THE GROUPS THAT REVIEWED THE RISKS THERE WAS THAT WAS SOMETHING THAT WE SHOULD NOT UNDERTAKE AND THIS IS ONE OF THOSE CIRCUMSTANCES WHERE THE CONTRIBUTIONS FROM INDUSTRY SHOULD BE OF BE A SETS AND NOT DOLLARS, THAT WAS THE CONCLUSION OF THE FOUNDATION FOR NIH AND MY OWN ADVISORY COMMITTEE SO THAT'S THE ROLE WE'RE GOING WITH. WE WILL NOT BE SHY POINTING OUT IMPORTANCE OF SHARING EVERYTHING THAT IS POSSIBLE TO KNOW FROM WHAT'S GONE ON IN INDUSTRY IN ORDER TO MAKE THIS WHOLE ENTERPRISE SUCCEED, I APPRECIATE YOUR HIGHLIGHTING THAT AS SOMETHING THAT DESERVES ATTENTION TOMORROW >> THE THREE MEMBERS OF THE HEAL PARTNERSHIP COMMITTEE WHO ARE ON THIS GROUP ARE KRISTIN, KEN AND JUDY. THEY WILL BE THE EMISSARIES WHO WILL REPORT BACK FROM THAT COMMITTEE AND TELL US ABOUT THE DISCUSSIONS THEY HAVE HAD, AND PROVIDE ANY MATERIALS OR PRODUCTS THAT HAVE BEEN DEVELOPED THROUGH THAT COMMITTEE FOR THIS GROUP TO HAVE A ROBUST DISCUSSION AND WE WILL HOLD THAT IN MAY. I WOULD ALSO ADD I THINK SOME OF THE REALLY INTEGRATED AND LEARNING APPROACHES THAT CLINT DESCRIBED FOR EPPIC-Net, THAT'S WHAT WE GET OUT OF IT AS A RESEARCH COMMUNITY. WE TEST THE ASSETS BUT WE GET ALL THE INFORMATION AND THE INTEGRATION OF DIFFERENT BIOMARKER STUDIES OR INTEGRATION OF DATA TYPE HARMONIZATION, WE LEARN FROM THE TESTING AND SO AS A COMMITTEE AND AS A WORKING GROUP WE'LL TURN TO YOU TO SAY HOW DO WE DO THIS IN A WAY THAT'S MOST FRUITFUL FOR RESEARCHERS FOR THOSE THAT ARE NOT PART OF THE NETWORK BUT PART OF THE BROADER COMMUNITY. >> I WANT TO GET BACK TO THE POINT THAT DIANA RAISED ABOUT RESILIENCE. WHAT ABOUT PEOPLE WHO DO MANAGE TO RECOVER FROM EPISODE OF ACUTE PAIN WHO DO NOT TRANSITION, WHAT ARE THE BIO, SOCIAL CHARACTERISTICS, SOCIAL ARE IMPORTANT BUT OTHER WITHIN THE INDIVIDUAL, MIND AND BODY, SAME FOR OPIOIDS, PEOPLE ABLE TO RECOVER AND THEN NOT RELAPSE, SO WE SHOULD FOCUS ON POSITIVE OUTCOMES AS WELL AS OF COURSE NEGATIVE ONES TOO. >> POINT WELL TAKEN. >> ONE OF THE THINGS WE KNOW, WE KNOW FOR MANY YEARS, IT WAS A LESSON TO ME, ONE ON ONE, WHEN I STARTED TO WORK IN THE FIELD, ONE MARKER OF SUCCESS IS SOCIAL STRUCK STRUCTURE. IF YOU HAVE FAMILY AND MEDICAL SUPPORT YOU DO BETTER THAN IF YOU HAVE A MUCH LESS SEVERE ADDICTION, YOU DON'T HAVE THAT, YOU'RE LOST AND WITHDRAWN. IT IS CATEGORICAL. BRINGING FORTH DISCUSSIONS THINKING INTO RECOVERY, ENSURING PLATFORMS OF SUPPORT ARE AVAILABLE FOR THOSE THAT ARE ADDICTED. >> I THINK WE'RE WINDING DOWN. AND REBECCA, MAYBE I COULD ASK YOU TO TELL US WHAT THE NEXT STEPS AND PLANS ARE, WE'LL TAKE A PHOTO IN FRONT OF OUR NOW FAMOUS ARTWORK. >> THANK YOU, FRANCIS. THANK YOU TO THE GROUP FOR PARTICIPATING TODAY. ALSO FOR YOUR PATIENCE, AND CAN-DO SPIRIT IN THE PAST COUPLE MONTHS WHEN WE'VE BEEN CALLING ON YOU A LOT FOR YOUR TIME AND FILLING OUT FORMS AND WE'RE GOING TO CONTINUE TO ASK FOR THAT. I WILL CONTINUE TO ASK FOR THAT. JUST SO IT DOESN'T GET LOST WE DID SET THE DATE OF OUR NEXT MEETING, MAY 17, HERE IN BETHESDA, MARYLAND. NEXT STEP WILL BE POLLING FOR THIS AUGUST MEETING, THAT'STHE ONE BECAUSE OF THE TIMING OF OUR FISCAL YEAR AND TIMING OF THE DIFFERENT INSTITUTE AND CENTER ADVISORY COUNCILS THROUGH WHICH THIS GROUP WILL MAKE ITS RECOMMENDATIONS AND FINDINGS, IT'S LIKE LIKELY THIS WILL LAND IN LAST TWO WEEKS OF AUGUST, WHEN EVERYONE IS AT THE BEACH, WE'LL ASK FOR YOUR FLEXIBILITY AND ALSO TURN TO YOU AND FRANCIS ALLUDED TO THIS BUT THIS WAS OUR FIRST MEETING SO WE WANTED TO GIVE YOU AN OVERVIEW OF ALL OF THE THINGS THAT HEAL IS DOING BUT WE DON'T KNOW ALL THE DIFFERENT KINDS OF CONTRIBUTIONS THAT YOU'RE GOING TO BE ABLE TO MAKE AND SO IF AFTER DIGESTING AND THINKING ABOUT TODAY'S MEETING THERE ARE WAYS OUTSIDE OF WHAT WE'VE OUTLINED YOU FEEL WOULD BE APPROPRIATE, ENGAGING WITH HEAL RESEARCH, WITH US, PLEASE FEEL FREE TO DROP ME A LINE OR SET UP A CALL TO DISCUSS IT BECAUSE I THINK THERE WERE A COUPLE THREADS AN THEMES TODAY THAT WE MIGHT WANT TO PURSUE. SO PAY ATTENTION TO THE E-MAIL THAT COMES FOR POLLING FOR AUGUST, DON'T LEAVE BECAUSE WE'LL HAVE A GROUP PHOTO, BUT THANK YOU VERY MUCH. [APPLAUSE]