I WANT TO WELCOME EVERYONE TO THE 130TH MEETING OF THE NATIONAL ADVISORY COUNCIL ON DRUG ABUSE. I WANT TO WELCOME OUR AD HOC MEMBERS AND HERE THEY ARE. BASICALLY WE HAVE NEW MEMBERS, I PILE JIEZ FOR THOSE THAT HAVE HEARD THE PRESENTATION BEFORE BUT BECAUSE THIS IS RECORDED AND MANY PEOPLE ARE NOT PART OF THE GOVERNMENT, THEY DIDN'T SEE THE CLOSED ONE, SO I'M GOING TO INTRODUCE YOU ALL AGAIN. SO BEAR WITH ME. FIRST IT'S A PLEASURE TO HAVE DR. GAIL PROFESSOR AND CHAIR OF THE DEPARTMENT OF EMERGENCY MEDICINE AT YALE UNIVERSITY SCHOOL OF MEDICINE AND PHYSICIAN IN CHIEF OF EMERGENCY SERVICES AT THE YALE NEW HAVEN HOSPITAL. SHE'S INTERNATIONALLY KNOWN FOR HER RESEARCH IN ADDICTIONS WORKING WITH EMERGENCY DEPARTMENT POPULATIONS AND FOR MENTORING PHYSICIAN SCIENTISTS TO DEVELOP INDEPENDENT RESEARCH CAREERS. FOR THE PAST 25 YEARS, SHE HAS DEVELOPED AND TESTED PSYCHOSOCIAL AND PHARMACOLOGICAL INTERVENTIONS FOR ALCOHOL, OPIOID AND OTHER SUBSTANCE USE DISORDER AND SHE HAS ALSO TRANSFORMED OUR PERSPECTIVE ABOUT HOW TO USE THE EMERGENCY DEPARTMENT FOR THE SCREENING AND EARLY INTERVENTIONS FOR OPIOID USE DISORDER. SO GAIL, IT'S A PLEASURE TO HAVE YOU. OUR SECOND AD HOC MEMBER IS A PROFESSOR OF PHARMACOLOGY AND BIOLOGICAL SCIENCES AT MOUNT SINAI WITH APPOINTMENTS IN PHARMACOLOGY AND SYSTEM THERAPEUTICS, PSYCHIATRY AND NEUROSCIENCES. SHE'S ALSO THE DEAN FOR ACADEMIC DEVELOPMENT AND ENRICHMENT AS WELL AS THE DIRECTOR OF THE INTERDISCIPLINARY TRAINING IN DRUG ABUSE RESEARCH PROGRAM. IN HER RESEARCH, SHE HAS PURSUED SEVERAL LINES OF INVESTIGATION, INCLUDING RECEPTOR DIMARY STATION, BIOSYNTHESIS AND OPIOID ADDICTION. HER CURRENT WORK USES A COMBINATION OF CLASSIC AND MODERN TECHNIQUES IN MOLECULAR PHARMACOLOGY TO EXPLORE THE NOVEL PROPERTIES OF RECEPTOR ENTERODIMERS AND CUTTING EDGE NEUROPROTEOMIC TECHNIQUES TO ANALYZE MORPHING INDUCED CHANGES INTO THE LEVEL OF SYNAPTIC -- AND NEUROPEPTIDES. SO WELCOME. THE THIRD PERSON I WANT TO INTRODUCE IS DR. CARLOS DELL RIO, HUBER PROFESSOR AND CHAIR OF THE HUBER DEPARTMENT OF GLOBAL HEALTH AND PROFESSOR OF EPIDEMIOLOGY AT THE SCHOOL OF PUBLIC HEALTH AT EMORY UNIVERSITY. HE'S ALSO PROFESSOR OF MEDICINE IN THE DIVISION OF INFECTIOUS DISEASES AT THE SAME UNIVERSITY. HIS RESEARCH FOCUSES ON THE EARLY DIAGNOSIS, ACCESS TO CARE, COMPLIANCE ARE ANTIRETROVIRAL THERAPY AND THE PREVENTION OF HIV INFECTIONS. HE HAS WORKED OVER TWO DECADES IN HOSPITALS AND CLINICS WITH HARD TO REACH POPULATIONS TO IMPROVE OUTCOMES OF THOSE INFECTED WITH HIV AND TO PREVENT INFECTIONS OF THOSE AT RISK. ASIDE FROM HIS WORK IN LANT TA, HE CONDUCTS HIV WORK INTERNATIONALLY IN KENYA, ETHIOPIA, THAILAND AND THE COUNTRY OF GEORGIA. AND THEN SO CARLOS, WELCOME. THEN LAST BUT NOT LEAST IS DR. DR. CHRISTIAN, CHIEF SCIENTIFIC OFFICER WHICH AIMS TO DEVELOP PRODUCTS AND SERVICES THAT ADDRESS THE NEEDS OF PATIENTS WITH DRUG ADDICTION. HE BEGAN HIS CAREER AT THE UNIVERSITY IN BELGIUM AND THEN CAME TO THE NATIONAL INSTITUTE FOR DRUG ABUSE IN BALTIMORE IN OUR INTRAMURAL PROGRAM FROM WHERE HE ACTUALLY THEN DID RESEARCH AT PRINCETON UNIVERSITY, AND AT THE FEDERAL INSTITUTE OF TECHNOLOGY IN ZURICH. HE HAS MORE THAN 25 YEARS OF LEADERSHIP EXPERIENCE IN THE NEUROSCIENCE, SPANNING THE ACADEMIC, GOVERNMENTAL, AND INDUSTRIAL SECTORS. ACROSS BOTH EUROPE AND THE UNITED STATES. SO CHRISTIAN, WELCOME. THIS IS THE BAD PART, ACTUALLY WE HAVE TO SAY GOODBYE TO OUR VERY APPRECIATED COUNCILMEMBERS, AND I HAVE HERE DIPLOMAS TO GIVE YOU, AND SO ACTUALLY THESE ARE DIPLOMAS THAT ARE SIGNED BY FRANCIS COLLINS ACTUALLY, SO -- AND IT IS A REFLECTION OF HOW MUCH WE VALUE YOUR PARTICIPATION PARTICIPATION, SO IT'S SYMBOLIC. WE'RE ACTUALLY LETTING GO OF FIVE OF YOU, WE'RE NOT GOING TO REALLY LET YOU GO BECAUSE WE'RE GOING TO CONTINUE TO COUNT ON YOU FOR YOUR SCIENTIFIC EXPERTISE AND ADVICE IN MANY OF THE THINGS WE HAVE AHEAD, BUT AS PART OF THE COUNCIL IS THE TIME FOR US TO SAY GOODBYE, AND I'M GOING TO BE GIVING YOUR NAMES SO WHEN YOU COME OVER, I'LL GIVE YOU YOUR DIPLOMAS AND THEN I THINK THERE'S A PHOTOGRAPH TO BE TAKEN, RIGHT? SO FIRST ONE IS JUDITH AUERBACH. JUDY? DO WE TAKE PICTURES? ALL TOGETHER? THEN JULIE BLENDE. BLENDY. TIME PASSED SO RAPIDLY, IT'S HORRIBLE! THANKS VERY MUCH. THIRD ONE IS JOHN CARNEVALE, ALSO THE SAME, I CAN'T BELIEVE, JOHN, THIS TIME HAS PASSED AND YOU'RE LEAVING US FROM COUNCIL, BUT I KNOW WE CAN ALWAYS COUNT ON YOU, SO THANK YOU VERY MUCH. THEN ARTHUR DEAN, TOO, IT'S SHOCKING IN MY BRAIN, BUT ARTHUR, WHAT CAN I SAY? AND FINALLY, STEFFANIE STRATHDEE, I AM SAD TO SEE YOU GO FROM COUNCIL BUT I WILL SEE YOU IN MANY OTHER THINGS. SO ALL OF YOU COME HERE SO JOSIE CAN TAKE A PICTURE. COME ON, GUYS. >> I ASSUME NEW MEMBERS DON'T GET A PICTURE UNTIL THEY ARE OFFICIAL? >> YES, THEY SHOULD NOT -- NOT UNTIL THEY'RE OFFICIAL. >> PROBABLY IN 2020? [LAUGHTER] >> SADLY, THAT MAY BE TRUE. >> NO, HOPEFULLY NOT. NOW, I HAVE TO READ, GUYS. THE GOVERNMENT IN THE SUNSHINE ACT AND THE FEDERAL ADVISORY COMMITTEE ACT REQUIRES THAT AS MANY ADVISORY COMMITTEE MEETINGS AS POSSIBLE BE OPEN TO THE PUBLIC. THIS INCLUDES MEETING OF THE NATIONAL ADVISORY COUP ON DRUG ABUSE. TODAY'S MEETING IS OPEN TO THE PUBLIC AND IS AVAILABLE TO THE PUBLIC VIA WEBEX. IN ADDITION, TODAY'S SESSION IS BEING AUDIO RECORDED AND TRANSCRIBED. MINUTES OF THE MEETING WILL BE AVAILABLE ON THE NIDA HOME PAGE. ALL OF YOU COUNCILMEMBERS ALREADY RECEIVE THE MINUTES ELECTRONICALLY AND THE COPY IS IN THE COUNCIL BOOK UNDER NIDA. NOW WE NEED TO VOTE ON NIDA MAY 2018 COUNCIL MEETINGS AND MAY 2018 -- MINUTES. ASK FOR MOTION FOR APPROVAL. SECOND? ALL OF THOSE IN FAVOR? AND MOTION IS CARRIED. I'M GOING TO ANNOUNCE THE FUTURE COUNCIL DATES, AND SO THE NEXT ONE FOR THE FIRST ONE FOR NEXT YEAR IS FEBRUARY 13TH, 2019. THEN ON MAY 14, WE HAVE THE NIDA ADVISORY COUNCIL MEETING AND THE FOLLOWING DAY ON MAY 15TH, THE CRAN JOINT COUNCIL MEETING AND ONE YEAR FROM NOW, ON SEPTEMBER 5, WE'LL HAVE THE LAST MEETING OF THE YEAR. WITH THAT, I'M GOING TO GO AHEAD AND PRESENT THE COUNCIL. THIS ACTUALLY IS A PARTICULARLY ACTIVE TIME FOR ALL OF US BECAUSE OF THE OPIOID CRISIS AND THE FACT THAT BASICALLY NOW THERE HAVE BEEN RECOGNITION BY HHS OF THE IMPORTANCE OF RESEARCH IN HELPING ADDRESS THE OPIOID CRISIS AND, OF COURSE, THIS FALLS CLEARLY WITHIN THE MISSION OF THE INSTITUTE, AND WE HAVE BEEN GRANTED SIGNIFICANT AMOUNT OF RESOURCES TO ADDRESS SOME OF THE GAP AREAS THAT CAN HELP US ADVANCE OUR INITIATIVES. AND IF I CAN ASK YOU TO TURN ON THE LIGHTS A LITTLE BIT, LIGHTS DOWN ACTUALLY PROMOTES SLEEPY SLEEPINESS, SO I WANT ALERTNESS. SO THIS IS THE STRUCTURE OF THE INSTITUTE CURRENTLY. WE HAVE ALL OF THE DIRECTORS AND THE LEADERSHIP POSITIONS. AS YOU KNOW, THE LAST POSITION WE HAVE FILLED WAS THE ONE OF THE DIVISION OF THERAPEUTICS AND MEDICAL CONSEQUENCES, AND WE WERE VERY LUCKY TO BRING HIM FROM WHERE HE HAD ACTUALLY ALREADY PLAYED A VERY IMPORTANT ROLE IN THE DEVELOPMENT OF MEDICATIONS RELATED TO BRAIN DISEASES, AND LAST COUNCIL HE WAS NOT HERE BUT TODAY HE IS, SO CAN YOU RAISE YOUR HAND SO THAT THEY CAN -- THOSE IN THE WEB CAN LOOK AT YOU. HE HAS BEEN HERE FOR THREE MONTHS BUT IN THAT PERIOD OF TIME, I ACTUALLY WAS JUST THINKING ABOUT IT, IT'S SORT OF LIKE HE ALREADY HAS DONE WHAT I WOULD HAVE EXPECTED TO TAKE SOMETHING LIKE 10 OR 12 MONTHS. SO WE'RE VERY, VERY PLEASED TO HAVE HIM HERE, AND IN -- DIRECTING AND LEADING THE DIVISION THAT IS FUNDAMENTAL FOR OUR ABILITY TO ACTUALLY HELP INDIVIDUALS SUFFERING FROM A SUBSTANCE USE DISORDER. BUDGET UPDATE, THERE ARE MANY THINGS THAT ARE NOT IN OUR BUDGET UPDATE. BASICALLY THIS IS THE ACTUAL ON 2017 AND OPERATING PLANS, BUT ON 2018, THERE WERE $250 MILLION NEW MONEY ALLOCATED TOWARDS THE OPIOID CRISIS, SPECIFICALLY RELATED TO OPIOID USE DISORDER, AND ANOTHER $250 MILLION THAT WERE ALLOCATED BUT TO ADDRESS THE ISSUES THAT RELATE TO BETTER TREATMENT OF PAIN, AS A MECHANISM AND A STRATEGY TO DECREASE THE PRESCRIPTION OF OPIOIDS AND THE AVAILABILITY THAT THEN FAVORS THEIR DIVERSION AND ABUSE. THE MONEY WAS ALLOCATED TO NIH, AND THE NAME NIDA FOR THE OPIOID COMPONENT, AND NIDS FOR THE PAIN COMPONENT, BUT THE PROJECTS ARE BEING DECIDED AT THE DIRECTOR'S LEVEL, BUILDING 1 ACTUALLY EVALUATES PROJECTS THAT ARE SUBMITTED BY THE DIFFERENT INSTITUTES, AND THEN THE MONEY IS ALLOCATED SO THEY CAN BE CARRIED ON. THIS MONEY IS BASICALLY AS I SAY ASSIGNED AS AN INSTITUTE TO US, BUT THE FUNDS THEMSELVES, HOW THEY ARE GOING TO BE USED, WILL BE DEPENDENT ON THE MERITORIOUS PROPOSALS. THAT'S WHY I HAVE NOT PUT THEM ON OUR BUDGETS FOR 2018 ITSELF. EVEN THOUGH THIS MONEY IS FOR 2018, WE HAVE THE CAPABILITIES OF ACTUALLY USE IT ALSO FOR 2019 PROJECTS, WHICH IS VERY USEFUL DUE TO THE FACT THAT WE HAVE VERY, VERY LIMITED TIME TO BE ABLE TO DEPLOY THEM IN A WAY THAT IS -- ENSURES US THAT WE WILL BE SUCCESSFUL IN BRINGING UP THE BEST PROJECTS, AND THAT REQUIRES AN ENORMOUS AMOUNT OF EFFORT FROM NIDA STAFF AND ALSO FROM ALL OF YOU WHO HAVE HELPED WITH SOME IDEAS AND WITH REVIEWS REVIEWS. THIS JUST GETS YOU A PERSPECTIVE OF THE RELEVANT INVESTMENT OF THE MAIN AREAS OF SCIENCE THAT WE SPEAK. THE DIVISION OF NEUROSCIENCE AND BEHAVIOR, THAT IS VERY APTLY LED BY DR. VAL TINO, ACCOUNTS FOR ABOUT 38% OF OUR BUDGET. ONE OF THE THINGS I WANT TO HIGHLIGHT IS THAT WE WANT TO ACTUALLY TRANSLATE -- AND EVEN THOUGH THESE SEEM TO BE SORT OF LIKE BOUNDARIES, WE ACTUALLY WANT TO ENHANCE THE TRANSLATION OF BASIC SCIENCE RESEARCH INTO THE OTHER ARENAS. CLEARLY AS IT RELATES TO THE DIVISION OF THERAPEUTICS AND MEDICAL CONSEQUENCES, THIS IS A VERY NATURAL PROGRESSION. THE FUNDINGS THERE ARE 15%, WE HAVE ALWAYS BEEN VERY, VERY PROACTIVE TO TRY TO INCREASE OUR FUNDING FOR MERITORIOUS PROPOSALS, BUT THIS IS, AGAIN, CHALLENGING TO BE ABLE TO SUCCESSFULLY BRING MEDICATIONS INTO THE CLINIC. THEN THE DIVISION OF EPIDEMIOLOGY SERVICES AND PREVENTION RESEARCH THAT IS VERY ABLY LED BY CARLOS BLANCO IS 28% 28%, AND THAT, TOO, PROVIDES US AN OPPORTUNITY NOT JUST TO TRANSLATE SOME OF THE FINDINGS FROM THE BASIC NEUROSCIENCE BUT ALSO IMPORTANTLY TO LEAD US INTO A BETTER UNDERSTANDING ABOUT HOW MEDICATIONS THAT ARE BEING USED ACTUALLY ULTIMATELY AFFECT OUTCOMES. AND INCREDIBLY IMPORTANT FOR US IS THE CENTER FOR THE CLINICAL TRIALS NETWORK, WHICH IS 4% OF OUR FUNDING, AND THAT'S VERY ABLY LED, CLINICAL TRIAL NETWORKS THAT WE'RE ABLE TO RAPIDLY DEPLOY NEW TREATMENTS AND INTERVENTIONS TO EVALUATE THAIR EFFECTIVENESS ONCE THERE HAS BEEN DATA TO SHOW THEIR EFFICACY. IT'S ALSO AN EXTRAORDINARY RESOURCE TO GENERATE PARTNERSHIPS WITH HEALTHCARE, AND IN THE PROCESS, TRAIN AND EDUCATE RESEARCHER -- IN RESEARCH THAT RELATES TO CLINICAL WORK ON SUBSTANCE USE DISORDERS. IMPORTANTLY TOO, THE LAST ONE IN OUR INTRAMURAL RESEARCH THAT ALSO HAS BEEN INCREDIBLY LED, NOT JUST THE DEVELOPMENT OF KNOWLEDGE, PREPREDOMINANTLY MOST OF THE EFFORT HAS BEEN ON BASIC NEUROSCIENCE BUT THERE'S ALSO EXPANDING IN THE CLINICAL COMPONENT. AND AN OPPORTUNITY FOR US TO PARTNER WITH MEDICATION DEVELOP. SO WHAT'S NEW AT THE NIH? WHAT I WANT TO HIGHLIGHT BECAUSE IT'S SO VERY RELEVANT FOR US IS THE BRAIN INITIATIVE. IT PROVIDES US WITH TOOLS AND CHARACTERIZATION OF NEURONS THAT ALLOW US TO UNDERSTAND BETTER AND TO APPLY THEM TO THE INVESTIGATION OF EFFECTS OF DRUGS IN THE BRAIN AND ULTIMATELY OF THE CONSEQUENCES OF REPEATED DRUG USE, INCLUDING ADDICTION. WHAT HAS BEEN THE MONEY DEPLOYED FOR THESE, THERE'S BEEN BASICALLY AS OF NOW 345 TOTAL BRAIN AWARDS, IN 2017, THERE'S 110 IN NEW INVESTIGATORS IN 2017, 178 FOR A TOTAL OF 504 SINCE THE BRAIN WAS INITIATED IN 2014. THE TOTAL INVESTMENT AS OF NOW IS $548.3 MILLION. MOST OF THE MONEY THAT HAS BEEN ALLOCATED FOR BRAIN HAS NOT BEEN DEPLOYED. YOU CAN SEE IT'S ACTUALLY NOT HOMOGENEOUS BUT IT HAS UPS AND DOWNS, BUT IMPORTANTLY IN 2023, THERE WOULD BE A MASSIVE INFLUX OF MONEY FOR $700 MILLION FOR DEVELOPMENT OF -- AND TECHNOLOGIES AND NOWT OPPORTUNITY HAS BEEN EXPANDED TO TRY TO ACTUALLY UTILIZE THESE TOOLS TO UNDERSTAND BETTER THE PAIN ITSELF AS A NEUROBIOLOGICAL PROCESSES, AND ALSO WE WANT TO INCENTIVIZE RESEARCHERS TO USE THESE BRAIN TOOL SET TECHNOLOGIES TO APPLY IT FOR THE INVESTIGATION OF OPIOID USE DISORDERS. BECAUSE OF THE SIGNIFICANT INCREASE IN BUDGETS THAT HAVE BEEN GIVEN ON BRAIN AND THE COMPLEXITY OF WHAT IT'S DOING, IT'S ACTUALLY BECOME CLEAR THAT THEY NEEDED A SPECIFIC DIRECTIVE TO OVERSEE BRAIN THAT WILL BE PART OF THE NATIONAL I INSTITUTE OF NEUROLOGICAL DISEASES, BUT THAT COULD WORK WITH ALL OF THE INSTITUTES THAT ARE PART OF BRAIN. SO FOR THE PAST YEAR, WE HAVE HAD TWO SEARCHES ACTUALLY TO IDENTIFY THE DIRECTOR FOR BRAIN. WE FINALLY HAVE SUBMITTED THE RECOMMENDATION OF A FEW CANDIDATES TO WALTER KOROSHETZ, WHO IS IN THE PROCESS OF MAKING THAT DECISION, SO I PREDICT THAT HOPEFULLY BY THE END OF THE YEAR, WE WILL HAVE THAT POSITION FINALIZED AND OFFICIALLY ACTUALLY MADE PUBLIC. WHAT ABOUT NIDA? WELL, NIDA IS ACTUALLY IN THE MIDST OF MULTIPLE THINGS, AND I THINK I STARTED BY ADDRESSING THE ISSUE OF THE OPIOID CRISIS, BUT EVEN THOUGH THE OPIOID CRISIS IS DEMANDING ENORMOUS AMOUNT OF OUR ATTENTION AS IT SHOULD, AT THE SAME TIME, MANY OTHER THINGS ARE HAPPENING IN THE COUNTRY THAT ARE SIGNIFICANT -- OF GREAT SIGNIFICANCE OVERALL BY THEMSELVES THAT WE CANNOT IGNORE. AND THAT RELATE, OF COURSE, TO SUBSTANCE USE DISORDERS, EXTRAORDINARY NOTABLE IS CHANGES IN LEGALIZATION PATTERNS WE HAVE FOR CANNABIS, AND THIS IS A NEW MAP, RIGHT NOW 30 STATES HAVE LEGALIZED MEDICAL MARIJUANA ALONG WITH D.C. , GUAM AND PUERTO RICO, BUT ALSO THOSE IN BLACK ARE ONES THAT ARE RECREATIONAL MARIJUANA. WHAT ARE THE CONSEQUENCES OF THESE CHANGES IN LEGALIZATION PATTERNS, THE CONSEQUENCES ARE THERE ARE MANY MORE PEOPLE SMOKING MARIJUANA, SO THE NUMBERS ARE PARTICULARLY NOTABLE IN INDIVIDUALS THAT ARE 18 OR OLDER. INTERESTINGLY THE DATA ON MONITORING THE FUTURE -- THE SAMHSA SURVEY, THEY HAVE CONSISTENTLY SHOWN THAT THERE ARE NOT INCREASES PER SE STABLE IN ADOLESCENTS BUT EVERYONE ELSE, THE RATE OF USE OF MARIJUANA IS GOING UP. AND THAT'S THE RATE OF USE THAT RELATES TO OCCASIONAL USE OR TO REGULAR DAILY USE. I THINK THIS IS EXTREMELY IMPORTANT BECAUSE WE HAVE TO ACTUALLY UNDERSTAND WHAT ARE ITS CONSEQUENCES. IN THE PROCESS, BECAUSE OF THE DIVERSITY BY WHICH THE STATES ARE LEGALIZING EITHER RECREATIONAL OR MEDICAL MARIJUANA, IT OFFERS US THE OPPORTUNITY TO INVESTIGATE WHAT ARE THE CONSEQUENCES OF THOSE POLICIES IN TERMS OF THE PREVALENCE RATES OF MARIJUANA USE AS WELL AS ITS ADVERSE EFFECTS OF. VERY IMPORTANTLY, I THINK IT ALSO HIGHLIGHTS THE NEED TO UNDERSTAND BETTER WHEN A STATE IS APPROVING MARIJUANA FOR ITS MEDICAL PURPOSES, HOW WIDELY UTILIZED IT IS AND HOW DOES THAT ULTIMATELY INFLUENCE THE OUTCOMES OF THOSE CONDITIONS FOR WHICH MARIJUANA IS BEING GIVEN. AS YOU KNOW OF PARTICULAR INTEREST HAS BEEN THE NOTION OF WILL THE USE OF MARIJUANA FOR THE TREATMENT OF PAIN AND YOU'VE ALREADY SEEN SEVERAL PAIBS THAT HAVE EMERGED AND HAVE SAID THIS IS THE SOLUTION FOR THE OPIOID CRISISMENT DON'T WORRY ABOUT IT, JUST PRESCRIBE MARIJUANA AND THEN YOU WON'T PRESCRIBE OPIOID MEDICATIONS. UNFORTUNATELY WHILE IT WOULD BE WONDERFUL FOR THESE TO BE TRUE, THE REALITY IS MUCH MORE COMPLEX THAN THAT AND IT INDICATES THAT, IN FACT, YOU HAVE TO RECOGNIZE THAT WHILE THERE MAY BE SOME INS STANCES ON INDIVIDUAL CASES WHERE THE USE OF MARIJUANA MAY HELP A PATIENT SERVING FROM CHRONIC PAIN THAT DOESN'T RESPOND TO ANYTHING ELSE, ON OTHER SITUATIONS, THE USE OF MARIJUANA MAY ACTUALLY MAKE SOMEONE MORE VULNERABLE TO THE USE OF ARE OTHER DRUGS INCLUDING OPIOIDS. THAT'S WHY FOR HIGHLIGHTING IN TERMS OF RESEARCH, I PICKED UP THIS PAPER THAT WAS RECENTLY PUBLISHED ON THE JOURNAL OF INTERNAL MEDICINE THAT ACTUALLY IDENTIFIED -- IT'S A PRIMARY CARE POPULATION IN WASHINGTON STATE THAT ACTUALLY LOOKS AT INDIVIDUALS AS A FUNCTION OF THEIR EXPOSURE TO CANNABIS, WHETHER IT IS KNOWN LESS THAN DAILY OR DAILY, AND THE PREVALENCE OF DIFFERENT CONDITIONS, AND CLEARLY YOU SEE THE DOSE-RELATED EFFECT ON TOBACCO USE, IT'S THE DAILY USERS THAT HAVE BASICALLY THREE TIMES, MORE THAN THREE TIMES THE TOBACCO USE. SAME THING, WHAT INTRIGUED ME ABOUT IT, ANY SUBSTANCE USE MARIJUANA TO EVERY DAY SIX FOLD HIGHER. WHEN YOU LOOK AT IT FROM ALSO ILLICIT DRUG USE, IT'S BASICALLY EIGHT FOLD HIGHER IN DAILY USERS. OF COURSE WHEN YOU HAVE DATA LIKE THIS ONE, YOU CANNOT DISSECT WHETHER THESE REFLECT THE FACT THAT PEOPLE THAT OVERALL ARE MORE VULNERABLE TO TAKE DRUGS, THEY MAY TAKE MARIJUANA BUT THEY MAY TAKE SOMETHING ELSE, AS OPPOSED TO A -- LINK. BUT THIS IS THE DATA THAT DISCLOSESNOT AS SIMPLE AS WE WOULD LIKE IT TO BE, THAT MARIJUANA ITSELF MAY BE PROTECTIVE, AND IN FACT IT BEGS THE QUESTION IN SOME INSTANCES IT MAY MAKE YOU MORE VULNERABLE TO THE ADDICTIVENESS OF OTHER DRUGS FOR WHICH OF COURSE THERE IS TWO BASIC NEUROSCIENTIFIC RESEARCH TO INDICATE THAT IS POSSIBLE. ALSO IT IS INTRIGUING ME A LOT AND I THINK WE HAVE TO KEEP AN EYE ON THIS BALL IS THE VERY FREQUENT ASSOCIATION THAT WE'RE SEEING BETWEEN DEPRESSION AND CANNABIS USE DISORDERS, AND THIS IS VERY RELEVANT BECAUSE AS WE'RE LOOKING AT THE OPIOID CRISIS AND THE OVERDOSE DEATHS, WE'RE ALSO RECOGNIZING THAT THERE IS A SIGNIFICANT INCREASE IN SUICIDALITY IN OUR COUNTRY. AND RECOGNIZING THAT DEPRESSION IS VERY FREQUENTLY CO-MORBID WITH SUBSTANCE USE DISORDER AND THAT INCLUDES CANNABIS AND OPIOIDS, AGAIN PROVIDES US THE OPPORTUNITY AND THAT DETERMINED WELL, WHAT IS THE NEUROBIOLOGY BUT IMPORTANTLY HOW DO WE ADDRESS IT AND WHAT ARE THE UNIQUE NEEDS OF THIS POPULATION. SO CLEARLY, CANNABIS IS SOMETHING THAT WE HAVE TO PAY ATTENTION AS A VERY IMPORTANT AREA AND MISSION WITHIN THE INSTITUTE THE. I THINK THAT IT'S CLEAR WE DON'T HAVE ANY TREATMENT FOR CANNABIS USE DISORDERS AND THERE IS AN URGENCY TO DEVELOP THEM SINCE OTHER THAN FROM THE LEGAL DRUGS IS THE HIGHEST NUMBER OF SUBSTANCE USE DISORDERS ARE CANNABIS USE DISORDERS, WE DON'T HAVE MEDICATIONS, BUT ALSO WE NEED TO RECOGNIZE THAT THERE OTHER MAJOR PROBLEMS EMERGING OF WHICH I JUST WANT TO MENTION ELECTRONIC DEVICES, AND THAT ARE BASICALLY OPENING UP THE DOOR FOR PEOPLE THAT OTHERWISE WHO HAVE NOT BECOME ADDICTED TONIC TEEN, TO TO NICOTINE THAT NOW HAVE AN ENTRY THAT INCREASES THEIR RISK FOR TOBACCO CONSUMPTION. TOBACCO CIGARETTES ARE ACTUALLY VERY, VERY PREVALENT, IT'S A NEW TECHNOLOGY BUT IT'S ADOPTED VERY, VERY RAPIDLY INFLUENCING ALL SEGMENTS OF THE POPULATION BUTPREDOMINANTLY YOUNG KIDS. SO WE CANNOT IGNORE THESE NEW DEVELOPMENTS ON TECHNOLOGY, NOR CAN WE IGNORE WHAT WE'RE STARTING TO SEE OVER THE PAST FEW YEARS OF A SIGNIFICANT INCREASE IN A NUMBER OF INDIVIDUALS THAT ARE OVERDOSING WITH DRUGS SUCH AS COCAINE AND THE EMERGENCE OF MET AMPHETAMINE IN THE UNITED STATES. WE CANNOT IGNORE THIS BECAUSE& MANY OF THE OVERDOSES THAT WE'RE ALSO SEEING ARE ACTUALLY PRESENTING THEMSELVES WITH A COMBINATION OF DRUGS. AND I TRAVEL THROUGH THE COUNTRY, THIS IS ONE OF THE THINGS THAT I HEAR WHEN I MEET WITH PEOPLE IN THE HOSPITALS, THAT THEY ARE WHAT IS MOST AN EVERYDAY OCCURRENCE RATHER THAN EXCEPTION, THE PATIENTS COMING IN WITH OVERDOSES ARE COMING IN WITH MULTIPLE DRUGS AND THIS IS CONSTANTLY CHANGING. OF COURSE THIS POSES AN ENORMOUS CHALLENGE WHEN IT COMES TO REVERSAL OF OVERDOSES, BUT ALSO WHEN IT COMES TO ACTUALLY TREATMENT OF INDIVIDUALS SUFFERING FROM OPIOID USE DISORDER BECAUSE THEY ARE CONFOUNDED WITH THESE OTHER ONES. AND I'M JUST SAYING, THESE TWO ILLUSTRATE THE THAT WHILE I'M GOING TO BE SPEAKING MOST OF THE REST OF MY PRESENTATION ON THE HEALING INITIATIVE FOR THE OPIOID CRISIS, WE CANNOT IN ANY WAY KEEP OUR EYES OFF THE OTHER VERY IMPORTANT ISSUES AFFECTING THE LIFE OF AMERICANS THAT GET EXPOSED TO THESE DRUGS. SO AS A BIGGER IMPORTANT COMPONENT IN RECOGNITION THAT ONE OF THE MOST IMPORTANT POPULATIONS THAT WE NEED TO PROTECT FROM THE EFFECTS OF DRUGS IS YOUNG INDIVIDUALS, CHILDREN AND ADOLESCENTS. THE ABCD WAS CONSTRUCTED AND INITIATED TO TRY TO GET US INFORMATION THAT IS SUBJECTIVE AND THAT IS SUFFICIENTLY POWERED TO LET US UNDERSTAND, FOR EXAMPLE, HOW THE EXPOSURE TO DRUGS DURING THAT TRANSITION FROM CHILDHOOD INTO ADULTHOOD INFLUENCED THE DEVELOPMENT OF THE HUMAN BRAIN. THIS IS A STORY THAT IS NOW BEING ABLE TO RECRUIT 1,100 -- 11,174 INDIVIDUALS, AND THE DEADLINE -- I MEAN THE THRESHOLD FOR RECRUITMENT IS 11,900, AND THIS, WE HAD TO OH INCREASE THE NUMBER OF RECRUITMENTS IN ORDER TO BE ABLE TO OVERSAMPLE FOR AFRICAN-AMERICANS AND TO OVERSAMPLE FOR KAU CAUCASIANS THAT COME FROM LOW SOCIOECONOMICAL ENVIRONMENTS. IT HAS BEEN ON TRACK AND NOW THE DATA HAS BEEN RELEASED, THE FIRST RELEASE OF THE DATA OCCURRED ALREADY, AND THERE IS A PATCH DATA RELEASE ANTICIPATED BY MID OCTOBER 2018, WHICH HOPEFULLY WE WILL GET THE WHOLE OF ALL OF THE DATASETS THAT HAVE BEEN COLLECTED AS CLOSE AS UP TO NOW. SO WE WOULD WELCOME AND ACTUALLY WE ARE DISCUSSION SCUSINGING WAYS TO FACIL ITATE AND TRAIN AND EDUCATE PEOPLE IT TO USE THIS DATABASE SO THAT IT CAN BE USED TO ASK IMPORTANT QUESTIONS ABOUT BRAIN DEVELOP DEVELOPMENT. THERE WAS A VOLUME THAT ACTUALLY CONTAINED A DIFFERENT DEVELOPMENT OF THE ABCD, ASSESSMENT STRATEGY THAT WAS PUBLISHED IN AUGUST 2018 AS A SPECIAL ISSUE, BUT DOWN THERE I'M HIGHLIGHTING WE HAVE OUR FIRST ORIGINAL DATA PAPER PUBLISHED OUT OF THE ABCD AND IT WAS PUBLISHED ON JAMA PSYCHIATRY A COUPLE OF MONTHS AGO. SO IT'S VERY EXCITING THIS PROJECT HAS ALREADY STARTED TO LEAD TO WHERE WE AIM IT TO DO FOR IT TO PROVIDE BASICALLY DATA FOR OTHERS TO UNDERSTAND HOW THE BRAIN DEVELOPS AND HOW IT'S AFFECTED BY SUBSTANCES AND HOW IT RELATES TO MENTAL ILLNESS. WE HAVE BEEN ON DISCUSSIONS, AGAIN, SUSAN WEISS -- IN TERMS OF HOW CAN WE DO A SIMILAR PROJECT THAT GOES FROM OUR LESSONS FROM -- BUT ALSO INFANCY BECAUSE THAT WOULD BE EXTRAORDINARY VALUABLE AND IN PARTICULAR, IT WOULD ENABLE US TO UNDERSTAND SOMETHING THAT HAS CHALLENGED MANY RESEARCHERS, WHICH IS WHAT ARE THE CONSEQUENCES OF FETAL EXPOSURE TO DRUGS. AS AN INFANT IS BORN. AND WE KNOW THAT, OF COURSE, THAT FOR THE CASE OF ALCOHOL, THAT THERE ARE VERY SERIOUS EFFECTS, WE ALSO KNOW BASED ON BEHAVIORAL CONSEQUENCES THAT NICOTINE EXPOSURE ALSO NEGATIVELY INFLUENCES OUTCOMES. BUT AS IT COMES TO OTHER DRUGS, THE DOCUMENTATION OF OBJECTIVE MARKERS OF DESTRUCTION OF NEUROCIRCUITRY HAS YET NOT BEEN AVAILABLE SO THERE'S SORT OF BEEN DISCUSSIONS IN TERMS OF HOW COULD ONE MOUNT SUCH A STUDY THAT COULD HELP US UNDERSTAND ULTIMATELY TO HOW THAT FETAL DEVELOPMENTAL STAGE ULTIMATELY INFLUENCES THE DEVELOPMENT OF TRAJECTORIES THROUGH NEONATES INTO INFANCY AN THEN INTO EARLY ADOLESCENCE. AND ULTIMATELY AS THESE CHILDREN GROW UP, HOW THEIR INFLUENCES OF THE ENVIRONMENT, EDUCATION, AND GENETICS ULTIMATELY DETERMINE THEIR BRAIN FUNCTION AND ARCHITECTURE. WITH THAT, I WANT TO JUMP INTO THE OPIOID CRISIS BECAUSE IT'S ACTUALLY WHAT HAS KEPT US BUSY OVER THE PAST I WOULD SAY OVER THE PAST MORE THAN ONE YEAR, BUT IT HAS JUST SORT OF -- THE INTENSITY IS GOING UP AND UP AND UP, HAS BEEN THE OPIOID CRISIS. RECOGNITION THAT RESEARCH CAN HELP US ADDRESS IT. THIS WAS ACTUALLY DESCRIBED ON HHS, THESE ARE THE FIVE PILLARS FOR ADDRESSING THE OPIOID CRISIS. ONE OF THEM IS, OF COURSE, HOW DO WE EXPAND ACCESS OF TREATMENT FOR OPIOID USE DISORDER AND PREVENTION OF OPIOID USE DISORDER, A SECOND ONE IS EXPANDING NALOXONE, A THIRD ONE IS WE OBVIOUSLY NEED TO STRENGTHEN THE PUBLIC HEALTH DATA AND REPORTING IN ORDER TO ACTUALLY BE ABLE TO MONITOR WHAT THE CONSEQUENCES OF WHAT WE ARE DOING IS HAVING ON OUTCOMES, BUT ON THERE BASICALLY SHOULD BE FOUR SINCE THEY HAVE TWO 1'S THERE, SUPPORT CUTTING EDGE RESEARCH, AND THAT'S WHERE NIH PLAYS A ROLE. THEN ON THE FIFTH ISED VANING THE PRACTICE OF IS ADVANCING THE PRACTICE OF PAIN MANAGEMENT. NIDA FALLS SQUARE INTO THE FOUR TOP ONES AND WE'VE ALSO BEEN -- ON PAIN MANAGEMENT, INVESTMENTS THE TRYING TO UNDERSTAND WHAT MEDICATIONS THAT TARGET OPIOIDS& CAN BE NON-ADDICTIVE AS WELL IMPORTANTLY HOW CAN YOU ADDRESS THE PAIN MANAGEMENT IN PATIENTS THAT HAVE BECOME ADDICTED TO THEIR OPIOID MEDICATIONS. IN JULY, FRANCIS COLLINS, WALTER KOROSHETZ AND MYSELF HAD A COMMENTARY IN JAMA TO ADDRESS THE $500 MILLION THAT I MENTIONED TO YOU OF WHICH 250 MILLION WOULD GO MORE OR LESS FOR OPIOID USE DISORDER-RELATED PROJECTS AND $250 MILLION WOULD GO TO PAIN-RELATED PROJECTS. OF COURSE THERE IS BLENDING BETWEEN THEM. IN THE OPIOID USE DISORDER, THERE IS PRIORITY BOTH FOR TREATMENTS FOR ADDICTION, THAT INCLUDES TREATMENTS FOR REVERSAL OF OVERDOSES, AS WELL AS IMPLEMENTATION SCIENCE THAT CAN MAXIMIZE OUR ABILITY TO ACTUALLY TAKE ADVANTAGE OF EVIDENCE-BASED INTERVENTIONS TO ACTUALLY MAXIMIZE THE LIKELIHOOD THAT WE CAN REVERSE THE CURRENT OPIOID CRISIS. AND THERE WAS ALSO IDENTIFIED AS A PRIORITY THE NEONATAL ABSTINENCE SYNDROME IN TERMS OF THE NEED TO DEVELOP BETTER INTERVENTIONS THAT CAN MINIMIZE THE NEED FOR NEONATAL INTENSIVE CARE UNIT OR MINIMIZE THE NEED OF GIVING OPIOIDS TO NEONATES. AND FINALLY, THE AREA ON ENHANCING PAIN MANAGEMENT, IT WAS RECOGNIZED THAT WE NEED TO HAVE MUCH MORE RESEARCH ON THE BASIC UNDERSTANDING ABOUT WHAT ARE THE FACTORS THAT LEAD IN A TRANSITION FROM ACUTE TO CHRONIC PAIN. CLEARLY RECOGNIZING THAT WE NEED TO ACCELERATE THE DEVELOPMENT OF PAIN MEDICATIONS THAT ARE EFFECTIVE, THAT ARE SAFE, INCLUDING NON-ADDICTIVE OPIOID MEDICATIONS OR NON-OPIOID MEDICATIONS THAT ARE VERY, VERY EFFECTIVE. THERE'S ALSO RECOGNIZED AND WE'VE BEEN WORKING NOW FOR MORE THAN A YEAR ON A PUBLIC-PRIVATE PARTNERSHIP WITH INDUSTRY THAT WOULD HELP US ACCELERATE THE OPPORTUNITY TO ENERGIZE THE INTEREST ON NEW PRODUCTS THAT CAN ULTIMATELY GET INTO THE MARKET. SO THOSE ARE THE ACTIVITIES HIGHLIGHTED AS PART OF THE HEAL INITIATIVE. SO WHAT ABOUT NIDA? SO WHAT I'M GOING TO GO DO NOW IS I'M GOING TO BASICALLY GO TOWARDS THOSE PROJECTS THAT WERE AOF PROVED BY THE NIH FOR FUNDING THIS HEEL MALE HEAL MONEY. THE DIRECTOR ULTIMATELY MAKES THE DECISION ON WHAT PROJECTS ARE MERITORIOUS. THIS REQUIRED THE CALL OF NIDA STAFF, WHICH THEY DID, THE INSTITUTE HAS BEEN WORKING EXTREMELY HARD TO COME UP WITH THESE PROPOSALS THAT THEN HAD TO BE REVIEWED AT BUILDING 1 AND ALSO DIFFERENT INSTITUTES THAN THOSE THAT WERE SELECTED. SO WE WERE ONE OF THE FIRST ONE THAT WAS SELECTED, THE NEED FOR PROTECTING RESOURCES TO ENHANCE MEDICATION DEVELOPMENT RESEARCH. AND THIS IS HIGHLIGHTED BY THE FACT THAT EVEN THOUGH WE HAVE BUPRENORPHINE, METHADONE AND EXTENDED RELEASE NALTREXONE, THAT UTILIZATION OF THESE MEDICATIONS IS VERY LIMITED AND THERE ARE ARE FACTORS THAT LEAD TO STIGMA THAT PLAY A ROLE INTO IT AS WELL AS LACK OF INFRASTRUCTURE, BUT ALSO THE DIFFICULTY AND THE LACK OF IN THE FACT THAT NOT ALL OF THE PATIENTS RESPOND TO THESE MEDICATIONS. ANOTHER IMPORTANT CHALLENGE WE HAVE IS IF YOU LOOK AT THE NUMBER OF INDIVIDUALS THAT ARE ABLE TO STAY ON TREATMENT WHEN THEY ARE GIVEN A MEDICATION IS THE APPROXIMATELY 50% AT SIX MONTHS, SO THE LATE OF RELAPSE IS RATE OF RELAPSE IS VERY, VERY HIGH, CAN WE DEVELOP ALTERNATIVES THAT IMPROVE THE LIKELIHOOD OF PATIENTS BEING KEPT ON TREATMENT FOR LONGER PERIODS. THE OTHER BIG CHALLENGE WE'VE OBSERVED IS AS THERE IS AN INCREASED LACING OF OPIOID DRUGS, WHETHER IT'S PRESCRIPTION OPIOIDS OR HEROIN WITH SYNTHETIC OPIOIDS LIKE FENTANYL OR THE ANALOGS, WE'RE BEING -- WITH SIGNIFICANT -- FOR OVERDOSING. ACTUALLY SOME OF THE PRESCRIPTIONS IN THE BLACK MARKET ARE BEING LACED WITH FENTANYL. ALSO DRUGS LIKE COCAINE AND METHAMPHETAMINE ARE ALSO BEING LACED WITH SYNTHETIC OPIOIDS. SO MOST OF THE CHALLENGE THAT EVERYBODY HAS BEEN DISCUSSING HAS BEEN THE DIFFICULTY OF REVERSING THE DOSES FROM FENTANYL WITH NALOXONE. SO YOU MAY BE ABLE TO REVERSE IT IN SOME INSTANCES JUST TO HAVE THAT INDIVIDUALS GOA GO BACK INTO UNCONSCIOUSNESS TWO, THREE, FOUR HOURS LATER, IN ONE INSTANCE ACTUALLY THERE IS A WRITTEN REPORT OF A PATIENT THAT WENT UP ACTUALLY AFTER THEY WERE REVERSED FROM AN OVERDOSE, EIGHT HOURS LATER, WENT INTO A COMA. AND THERE'S ALSO REPORTS OF THE NEED TO ACTUALLY SUSTAIN A NALOXONE DRIP FOR ACTUALLY LONGER THAN 24 HOURS. THESE ARE THE TYPE OF CHALLENGES THAT WE HAVE. SO THE NASAL NARCAN OR EVEN THE INJECTION -- ONE INJECTION PRODUCT ARE NOT BEING SUFFICIENTLY TO GUERIN TEET SURVIVAL OF PATIENTS OVERDOSING. AGAINST A UNIQUE OPPORTUNITY OF DEVELOPING ALTERNATIVES. SO THE GOAL OF THIS PARTICULAR INITIATIVE IS TO ADVANCE RAPIDLY THE DEVELOPMENT OF COMPOUNDS TO PREVENT AND REVERSE OVERDOSES AND TREAT THE DIFFERENT STAGES OF OPIOID USE DISORDERS. SO WHAT ARE SOME OF THE INCLUDED AREAS OF INTEREST? NEW FORMULATIONS OF CURRENTLY AVAILABLE MEDICATIONS. AND THIS IS THE LOW HANGING FRUITS BECAUSE IF YOU CAN EXTEND THE DURATION, FOR EXAMPLE, OF THE EXTENDED RELEASE NALTREXONE INSTEAD OF ONE MONTH, EVEN IF YOU EXTEND IT TO TWO MOBTS, YOU'RE ACTUALLY DOUBLING THE LIKELIHOOD OF THAT PATIENT BEING IN TREATMENT IN THE FIRST TWO MONTHS. AND WHILE THERE IS A SIGNIFICANT RATE OF RELAPSE OR IN THE FIRST SIX MONTHS, IF YOU LOOK AT THE TRY JEK TREES, MOST OF THOSE THOSELAPSES ARE OCCURRING WITHIN THE FIRST TWO MONTHS. SO IF YOU CAN SUSTAIN PATIENTS THERE, YOU ARE GAINING TIME AND I CREASE THE LIKELIHOOD THAT THEY WILL SUCCEED AND EVENTUALLY RECOVER. THERE'S ALSO CLEARLY -- WE NEED TO HAVE LONGER ACTING OPIOID ANTAGONISTS, WHETHER IT IS NALOXONE BY GIVING IT IN ENTIRE DOSES OR A WAY OF GIVING IT SEQUENTIALLY OR LONGER ACTING ANTAGONISTS. THERE IS CLEARLY A NEED, AS WELL AS DRUGS THAT WILL STIMULATE RESPIRATION OR THAT WILL IMPROVE OXYGENATION THROUGH THE LUNGS. IT'S ANOTHER IMPORTANT ONE BECAUSE INDIVIDUALS THAT ARE OVERDOSING ARE ALSO OVERDOSING WITH COMBINATION OF DRUGS THAT BY THEMSELVES ARE HAVING A RESPIRATORY DEPRESSING EFFECT THAT IS NOT COUNTERACTED BY AN OPIOID ANTAGONIST. AND THEN THERE IS OBVIOUSLY THE IMPORTANT ROLE THAT BASICALLY HAS BEEN HIGHLIGHTED BY BASIC SCIENCE THAT IDENTIFIED MULTIPLE -- VERY INTERESTING TARGETS THAT COULD BE USED FOR THE TREATMENT OF OPIOID ADDICTION SUCH AS IS THE CASE, FOR EXAMPLE, OF DOPAMINE D3 RECEPTOR ANTAGONIST AND MANY OTHER TARGETS AND THE IMPORTANCE OF IMMUNOTHERAPIES WHETHER IT'S VACCINES OR MONOCLONAL ANTIBODIES. FINALLY AN AREA THAT WE HAVE BEEN VERY, VERY PROACTIVE IN ENGAGING IS THE DEVELOPMENT OF MEDICATIONS THAT, BY THEMSELVES, MAY NOT JUST ACHIEVE THE MAIN OUTCOME, WHICH IS ABSTINENCE AND CLEAN URINES, BUT ACTUALLY GO AFTER SPECIFIC CONSTRUCTS THAT ARE PART OF THE PHENOTYPE OF OPIOID ADDICTION, AND THAT MAY BE INSOMNIA, THAT MAY BE CRAVING, DYSPHORIA, COGNITIVE IMPAIRMENT. AND BY NOD GUYING BY MODIFYING THEM, WE MA Y BE ABLE TO IMPROVE THE LIKELIHOOD OF PATIENTS BEING ABLE TO RECOVER. SO WHAT IS IT THAT WE HAVE DONE UP TO NOW? WE HAVE BASICALLY -- LET ME GO FIRST TO THE LOWER CHANGE IN FUNDS AVAILABLE, BECAUSE OF THE EXTRA MONEY THAT CAME THROUGH HEAL. WE HAVE TO CHANGE FROM -- TO COMMIT $10 MILLION IN EACH FISCAL YEAR IN DEVELOPMENT OF MEDICATIONS FOR OWED YOID USE DISORDER TO 70 MILLION IN THIS FISCAL YEAR OF DEVELOPMENT OF MEDICATIONS FOR OPIOID USE DISORDER. THE OTHER ISSUE WE'D HAD TO CHANGE HAS TO DO WITH SOME OF THE REQUIREMENTS OF THE HEAL MONEY. THE HEAL MONEY REQUIRES THAT MONEY COMES OUT OF THIS POTIPHAR FOR PROFIT -- DIRECTED IN MONEY OR IN KIND. AND SO WE HAD TO CHANGE ALL OF THOSE NOTICES OF REQUIREMENTS, WHETHER IT WAS THE DEVELOPMENT OF MEDICATIONS TO PREVENT OPIOID OVERDOSE OR STRATEGIC ALLIANCE OR THE GRANT OPPORTUNITIES AS THAT RELATES TO OPIOID TO HAVE THIS REQUIREMENT. AND THIS IS AGAIN ALSO PERTINENT FOR STTR OR FROM ANY OTHER TYPE OF -- THAT DOES PROVIDE FOR PROFIT. IN THE SCIENCE, I DO WANT TO HIGHLIGHT AN EXTREMELY INTERESTING FINDING THAT WAS PUBLISHED ON SIGH EBBS TRANSLATIONAL MEDICINE ON JUNE OF THIS YEAR, BECAUSE IT ACTUALLY SHOWS THE OPPORTUNITY THAT WE HAVE AND WHY BASIC SCIENCE IS SO VERY, VERY RELEVANT. IN THIS CASE, THE INVESTIGATORS ANALYZED POSTMORTEM BRAINS OF FIVE INDIVIDUALS THAT HAD DIED WITH A HEROIN USE DISORDER AND SEVEN CONTROLS AND THEY FOUND ACTUALLY THAT IN THE LATERAL HYPOTHALAMUS AND OTHER AREAS WHERE YOU EXPRESS -- EXPRESSING CELLS, THERE WAS A SIGNIFICANT INCREASE IN THE NUMBER OF -- IN THE BRAIN SO INDIVIDUALS WITH A HEROIN INDUCED DISORDER, AND THEY INCREASE BY 54%. THE SIZE OF THE CELLS WERE SMALLER BUT IT'S A SIGNIFICANT INCREASE. AND YOU CAN SEE THERE ARE THE NUMBERS AND ACTUALLY SOME EXAMPLES OF IMMUNO -- ON A POSTMORTEM BRAIN PATIENT CLEARLY INDICATING A SIGNIFICANT INCREASE IN THE CELLS THAT ARE NOW EXPRESSING HYPOCRETIN. THEN THEY TAKE THIS FINDING AND THEY DETERMINE CAN WE ACTUALLY REPLICATE THIS IN A CLINICAL MODEL, SO THEY ACTUALLY TREATED ANIMALS WITH MORPHINE AND SHOWED CHRONIC TREATMENT WITH MORE TEEN SIGNIFICANTLY INCREASED THE NUMBER OF CELLS EXPRESSING HYPOC RE. HYPOC -- HYPOCRETIN, ACTUALLY FOUND NON-EXISTENT IN THE BRAINS OF PEOPLE WITH NARCOLEPSY, WHO BASICALLY FALL ASLEEP, AND AS A ACTUALLY TARGETING AS ANTAGONISTS THE HYPOCRETIN RECEPTOR TO KEEP YOU AWAKE. SO ONE OF THE THINGS THAT BECOMES VERY RELEVANT IS IF YOU DON'T HAVE HYPOCRETIN AND YOU'RE ACTUALLY FALLING ASLEEP, IF YOU JUST FOLLOW THE CONTRARY LOGIC, BASICALLY IT MEANS YOU CANNOT FALL ASLEEP. AND THE QUESTION IS, COULD THIS HELP US WITH THE SEVERE PROBLEMS OF INSOMNIA THAT PATIENTS WITH OPIOID DISORDERS SUFFER FROM, AND THAT INCLUDES NOT JUST INDIVIDUALS THAT ARE ACTUALLY HEROIN USERS WITHOUT TREATMENT BUT EVEN INDIVIDUALS THAT ARE BEING TREATED WITH OPIOID AGONISTS, THE FACT THAT OPIOIDS AGONISTS MAY HAVE THIS DOWNSTREAM EFFECT. AND AGAIN, HIGHLIGHTING HOW PERHAPS THE HYPOCRETIN ANTAGONIST, WHICH IS ONE OF THE THINGS -- WHY DON'T WE TRY TO SEE IF A HYPOCRETIN ANTAGONIST CAN IMPROVE THE SLEEPING PATTERNS IN PEOPLE SUFFERING FROM AN OPIOID USE DISORDER WHICH IN PRINCIPLE COULD ALSO IMPROVE OUTCOMES. SECOND PROJECT THAT HAS BEEN APPROVED IS BASICALLY THE INTEGRATED TREATMENT, THE HEALING COMMUNITIES STUDIES. THIS IS A PROJECT THAT IS BEING LED BY DR. RADONA CHANDLER, AND SHE WILL BE GIVING AN UPDATE AND A PRESENTATION ON IT. IT HAS BECOME ONE OF THE HALLMARKS FOR THE WHOLE HHS AS A PROJECT TO ILLUSTRATE HOW THERE IS AN OPPORTUNITY TO USE SCIENCE NOT JUST TO ADVANCE KNOWLEDGE BUT ACTUALLY TO IMPLEMENT INTERVENTIONS THAT CAN DECREASE OVERDOSE MORTALITY, WHICH IS THE MAIN GOAL, TO SHOW THAT IF WE INTEGRATE EVIDENCE BASED INTERVENTIONS THAT RELATE TO TREATMENT AND PREVENTION, WE CAN SIGNIFICANTLY AFFECT THE MORTALITY ASSOCIATED WITH OPIOID OVERDOSES. AND USE THESE AS A PARADIGM ALSO TO DOCUMENT AND DEMONSTRATE WAYS BY WHICH THE AGENCIES CAN WORK WITH ONE ANOTHER, SO THIS PROJECT IS DONE IN VERY CLOSE COLLABORATION WITH SAMHSA, AS WELL AS OTHER AGENCIES, AND IT WILL TARGET TO GIVE BASICALLY GRANTS TO THREE SITES ACROSS THE UNITED STATES IN THREE DIFFERENT STATES THAT ACTUALLY DEMONSTRATE THEY HAVE A HIGH RATE OF MORTALITY THAN THAT OF THE GENERAL POPULATION, AND THEY WILL ALSO HAVE AT LEAST 30% OF THE COMMUNITIES THAT ARE GOING TO BE INCORPORATED INTO IT ARE BEING ROLLED OUT. IT WILL REQUIRE THAT IT ENGAGE THREE ELEMENTS: AND IT USES THE CASCADE OF CARE TO GUIDE THE INTERVENTIONS. RSM. WE HAD REQUESTS FOR INFORMATION, WE HELD A MEETING TO TRY TO OH GET AS MUCH INPUT AS POSSIBLE, AND WE HAD A NOTICE OF INTENT FOR THE FUNDING OPPORTUNITY ANNOUNCEMENT AND ESTIMATED PUBLICATION FOR THE ACTUAL FUNDING OPPORTUNITY TO BE IN SEPTEMBER. THERE'S GOING TO BE TWO OF THEM. ONE FOR A DATA COORDINATING CENTER AND THE OTHER ONE FOR RESEARCH SITES. THE THIRD PROJECT APPROVED AS PART OF THE HEAL INITIATIVE WAS EXPANDING THE CLINICAL TRIAL NETWORK. IT BECAME CLEAR THAT ONE OF THE MOST POWERFUL TOOLS THAT WE HAVE TOO ADDRESS THE OPIOID CRISIS IS LET'S TAKE ADVANTAGE OF THE HEALTHCARE SYSTEM. BUT BECAUSE IT HAS NOT TBRAN DIGSALLY VERY MUCH INVOLVED IN THE SCREENING OF SUN STANCE USE DISORDER, THAT REQUIRES THE DEVELOPMENT OF TESTING AND TRAINING ON HEALTHCARE PERSONNEL, IN THAT RESPECT TAKING ADVANTAGE OF THE CLINICAL TRIAL NETWORK WHICH IS VERY, VERY ABLY LED, PROVIDES US A BACKBONE WITH WHICH TO EXPAND OUR CONNECTIVITY WITH HEALTHCARE IN GENERAL AND IN FACT THE CLINICAL TRIAL NETWORK HAS BEEN DOING THAT OVER THE PAST YEAR, AND IT HAS SHIFTED FROM BEING PREDOMINANTLY A NETWORK THAT WORKS WITH TREATMENT PROGRAMS INTO A NETWORK THAT WORKS EXTENSIVELY WITH HEALTHCARE INCLUDING EMERGENCY DEPARTMENT AND PRIMARY HEALTHCARE PHYSICIANS. SO WE AIM TO HAVE A GREATER CAPABILITY OF SUCCESS WITH HEALTHCARE PROVIDERS INCLUDING SPECIALTY AREAS, BUT ALSO ACCESS TO AREAS IN RURAL COMMUNITIES WHERE THE CHALLENGES FOR TREATMENT ARE ACTUALLY MUCH MORE SIGNIFICANT AND ALSO IMPORTANTLY TO BE ABLE TO DEVELOP TRAINING FOR RESEARCHERS THAT CAN ACTUALLY HELP DEVELOP THOSE MODELS. FINALLY ULTIMATELY, WE HAVE A REGISTRY TO UNDERSTAND ULTIMATELY WHAT ARE THE TRAJECTORIES LONG TERM ON SUBSTANCE USE DISORDER AND OPIOID USE DISORDER VERY IMPORTANTLY, AND THE SECOND ONE THAT IS ALSO VERY RELEVANT IS WHAT ARE THE STANDARDS OF CARE ASSOCIATED WITH THE BEST OUTCOMES, AND HOW CAN WE MONITOR THE QUALITY OF CARE THAT IS BEING PROVIDED WITH PATIENTS SUFFERING FROM AN OPIOID USE DISORDER AND/OR A SUBSTANCE USE DISORDER. SO AMONG THE PROJECTS THAT ACTUALLY ARE GOING CERTAINLY AS YOU EXPAND ON THE CLINICAL TRIAL NETWORK, WE WANT TO TAKE ADVANTAGE OF ITS UNIQUE CAPABILITIES, WHICH IS GETTING ACCESS TO HEALTHCARE BUT ALSO BEING ABLE TO RUN COMPLEX PROJECTS IN A TIMELY FASHION. AND ONE OF THE QUESTIONS THAT HAS EMERGED THAT HAS NOT BEEN ADDRESSED THAT WOULD BENEFIT FROM THE CTN IS WHAT SHOULD BE THE DURATION OF TREATMENT ON SOMEONE GIVEN MEDICATION FOR AN OPIOID USE DISORDER. TRADITIONALLY WHEN YOU ASK THAT QUESTION, SOME PHYSICIANS SAY MAYBE FOR LEAVE. BUT LIFE. BUT WE HAVE NOT TESTED THAT. WE NOW HAVE EXTENDED RELEASE NALTREXONE, IT IS POSSIBLE FOR US TO CONDUCT A CLINICAL TRIAL THAT WOULD ENABLE US TO DETERMINE HOW LONG TO PATIENTS NEED TO BE ON MEDICATION AND WHAT ARE THE CHARACTERISTICS THAT DETERMINE WHEN CAN A PATIENT BE CONSIDERED THAT THEY CAN BE WEANED OFF THEIR MEDICATION OR NOT. AND ANOTHER EXTREMELY IMPORTANT AREA OF RESEARCH IDENTIFIED LAST YEAR IN ONE OF OUR MEETINGS FOR WHICH THE CTN CAN PLAY AN EXTREMELY IMPORTANT ROLE IS THAT OF WHAT DO WE DO WHEN SOMEONE HAS AN INCIPIENT OPIOID USE DISORDER? WHAT ARE THE BEST INTERVENTIONS? UNFORTUNATELY WE HAVE NO EVIDENCE WHATSOEVER WHAT IS THE BEST STRATEGY TO DO AN INTERVENTION THAT CAN BASICALLY PREVENT FURTHER DEVELOPMENT OF OPIOID ADDICTION IN SOMEONE THAT IS AT THOSE EARLY STAGES. SO WE HAVE RELEASED A NOTICE OF INTENT TO PUBLISH A FUNDING OPPORTUNITY FOR EXPANSION OF THE CTN. WE EXPECT THE FUNDING OPPORTUNITY ANNOUNCEMENT ITSELF TO BE PUBLISHED IN SEPTEMBER AND THE EXPECTED APPLICATION DATE IS IN NOVEMBER 2018. THE FOURTH INITIATIVE THAT WAS APPROVED IS BASICALLY THE JUSTICE COMMUNITY OPIOID NETWORK. SO THE HEALTHCARE INFRASTRUCTURE IS A VERY POWERFUL ONE FOR US TO TAKE ADVANTAGE FOR THE TREATMENT AND SCREENING OF OPIOID USE DISORDER BUT ALSO VERY IMPORTANTLY IS THE JUSTICE SETTINGS, JUST BECAUSE OF THE NUMBER OF INDIVIDUALS IN THE JUSTICE SYSTEMS SUFFER FROM OPIOID USE DISORDER. I WAS ACTUALLY TRYING TO GET SOME NUMBERS AND IT'S HARD FOR ME TO KNOW EXACTLY WHAT THE NUMBERS ARE, BUT THIS MORNING I WAS READING SOMETHING THAT IF YOU COMPARE THE RATE OF AN OPIOID USE DISORDER IN PEOPLE THAT ARE IN A JUSTICE SETTING VERSUS NOT IS FOUR FOLD HIGHER, AGAIN ILLUSTRATING THE UNIQUE OPPORTUNITY WE HAVE THERE TO DO AN INTERVENTION THAT CAN IMPROVE OUTCOMES. WE HAVE BEEN FUNDING RESEARCHERS THAT HAVE SHOWN THAT WHEN YOU INITIATE TREATMENT, WHETHER IT'S BUPRENORPHINE OR METHADONE WHILE IN THE PRISON SYSTEM, YOU ACTUALLY SIGNIFICANTLY IMPROVE YOUR OUTCOMES. THERE'S ALSO RESEARCH THAT I PRESENT IN COUNCIL IN THE PAST SHOWING THAT IF YOU INITIATE ACTUALLY AND YOU SUSTAIN THE TREATMENT FOR THE MEDICATION OF AN OPIOID USE DPIS DISORDER WHILE IN JAIL, YOU SPECIFICALLY REDUCE THE MORTALITY. SO HOW DO WE GENERATE MO MODELS THAT CAN EXPAND THE INTEGRATION OF CARE WHEN A PERSON IS RELEASED FROM PRISON OR JAIL INTO THE HEALTHCARE SYSTEM, WHAT ARE THE MODELS THAT ARE OPTIMAL FOR WORKING IN THIS SPACE? WE ALSO COME TO REALIZE THAT THE JUSTICE SETTINGS ARE EXTREMELY DIVERSE. AS A RESULT OF THAT, THERE HAVE BASICALLY -- THERE'S ALWAYS BEEN AN INTEREST IN JUSTICE SETTINGS AND RESEARCH. RADONNA CHANDLER, WHEN SHE WAS IN HER OTHER CAPACITY AT NIDA, DEVELOPED A VERY STRONG PROGRAM, WHEN WILSON COMPTON WAS THE DIRECTOR. NOW THEY'RE TAKING OVER AND ACTUALLY REALLY ENERGIZING THIS WHOLE AREA OF RESEARCH AND RECOGNIZING THAT WE NEED TO START TO KNOW FOR EXAMPLE HOW FREQUENTLY ARE MEDICATIONS BEING GIVEN IN PRISONS OR JAILS. YOU REALLY DON'T HAVE MUCH OF AN IDEA. WE KNOW IT'S VERY, VERY MINIMAL. IN, FOR EXAMPLE, WHAT ABOUT DRUG CORES, WHAT PERCENTAGE OF PEOPLE THAT GO THROUGH DRUG COURT ARE OFFERED MEDICATIONS FOR OPIOID USE DISORDER? IT'S RECOMMENDED BUT NOW WHAT WILL ULTIMATELY ARE THE OUTCOMES. SO WE NEED TO START TO UNDERSTAND WHY IS THE LANDSCAPE OF THE USE OF MEDICATIONS AND THE NATURE OF THE MAGNITUDE OF THE PROBLEM AND CREATE A NETWORK THAT THEN WILL ALSO LIKE WE HAVE WITH A CLINICAL TRIAL NETWORK FACILITATE OUR ABILITY TO IMPLEMENT RESEARCH AND ON THE ONE HAND GENERATE EVIDENCE BUT ALSO SHOW EFFECTIVENESS. WHERE ARE WE WITH -- ALL OF OUR PRIORITIES ARE ON TOP OF THAT SO IF YOU WANT TO LOOK AT IT WITH MORE DETAIL, BUT WE AWARDED A SUPPLEMENT TO CHESTNUT HEALTH SYSTEM TO CONDUCT A SURVEY OF THE AVAILABILITY OF MEDICATION-ASSISTED TREATMENT AND I'M TRYING TO GET RID OF THAT TERM AT LEAST IN MY LEXICON AND SPEAK ABOUT MEDICATION FOR OPIOID USE DISORDER IN JAILS AND PRISONS, AND I DO THAT IN ORDER NOT TO STIGMATIZE MEDICATIONS ANYMORE. I THINK THAT WE HAVE TO RECOGNIZE THAT THEY ARE MEDICATIONS. THE P.I. IS CHRISTY SCOTT AND THEN FOR THE -- WE HAVE A NOTICE TO INTENT FUNDING OPPORTUNITIES ANNOUNCEMENT FOR THE HEAL JUSTICE COMMUNITY OPIOID INNOVATION NETWORK ADVANCED ANALYTICS AND METHODOLOGY CENTER. WE ESTIMATE PUBLICATION FOR THE FUNDING OPPORTUNITY ANNOUNCEMENTS BY OCTOBER 1ST. HOPEFULLY WE CAN GIVE THE AWARD APRIL 1ST, 2019, AND TO START ON JUNE 1ST, 2019. THIS DOES NOT MEAN WE'RE NOT GOING TO BE DOING RESEARCH ON OTHER AREAS ON OPIOID USE DISORDER AND IN FACT, DR. VAL TINO AND HER TEAM HAVE ACTUALLY IDENTIFIED A SERIES OF PROJECTS THEY WOULD ACTUALLY LIKE TO BE ABLE TO LAUNCH TO UNDERSTAND MUCH BETTER THE NEUROBIOLOGY OF THE INDODGE JUST ENDOGENOUS OPIOID SYSTEM, THE MOLECULAR SYSTEM BY WHICH IT SIGNALS THE NEUROCIRCUITRY AND TAKE ADVANTAGE OF BRAIN TOOLS AND TECHNOLOGY. SO WE WILL, INDEPENDENT OF THIS MONEY, BE USING FUNDS FROM NIDA ITSELF TO ADVANCE BASIC ASPECTS OF NEUROSCIENCE THAT RELATES IT TO OPIOIDS. NOW, FROM THE ASPECT OF PAIN, WHAT WERE THE AREAS THAT WERE IDENTIFIED? AN AREA THAT WAS IDENTIFIED AS A PRIORITY IS THE NEUROBIOLOGY THAT LEADS ON THE TRANSITION FROM ACUTE TO CHRONIC PAIN. AND THIS WAS A PROPOSAL, WE HAVE BEEN WORKING ON AN ANNUAL BASIS FOR MANY YEARS, SO -- THE COMMON FUND AND DAVE THOMAS HAS BEEN A WARRIOR, NEVER GIVING UP, BUT EVERY TIME HE SUBMITTED A PROPOSAL, WE SAID NO, IT DIDN'T GET APPROVAL UNTIL THIS YEAR, WE FINALLY GOT A PROPOSAL FOR THE COMMON FUND, AND IT WAS DONE, OF COURSE, AS PART WITH PAIN CONSORTIUM OF WHICH, AGAIN, DAVID HAS REPRESENTED US AND I'M PART OF IT. AND IN THIS PROPOSAL, THE IDEA IS TO UNDERSTAND, FOLLOW PROSPECTIVELY PATIENTS THAT ARE GOING TO BE ON THEIR SURGERY AND DETERMINING WHICH OF THEM ARE GOING TO BE TRANSITIONING INTO CHRONIC PAIN AND DOING AN IN DEPTH CHARACTERIZATION, AND ANOTHER WILL BE PATIENTS SUFFERING FROM A RECENT MUSCULOSKELETAL TRAUMA, WHICH WILL BE FOLLOWED PROSPECTIVELY, WHICH GOES ON TO DEVELOP CHRONIC PAIN AND WHICH DO NOT, THERE WILL BE PHENOTYPE, GENOTYPE, IMAGE, OMICS OF ALL DIFFERENT CLASSES AND THE IDEA IS TO ACTUALLY TRY TO IDENTIFY BIOMARKERS THAT CAN UNDERSTAND PREDICTERS OF VULNERABILITY ON MARKERS THAT ENABLE US TO UNDERSTAND RESILIENCE, AND BASED ON THAT KNOWLEDGE, OF COURSE, WE CAN TRY TO IDENTIFY WAYS OF MANIPULATING IT AND DOING PREVENTION INTERVENTIONS AND THERAPEUTICS. SO BOTH NINDS AND NIDA ARE LEADING ON THIS COMMON FUND PROJECT. THIS IS CONSIDERED PART OF THE HEAL INITIATIVE. HEAL MONEY WILL BE DONE ON THE OTHER HAND TO INVEST ON A LARGE STUDY TO DETERMINE AND HELP IDENTIFY BIOMARKERS FOR PAIN. SO CURRENTLY WE ALL KNOW THAT THE WAY PAIN IS ASSESSED IS BY A SUBJECTIVE RATING SCALE ANSWERING THE QUESTION HOW MUCH ARE YOU IN PAIN FROM ZERO TO 10, ZERO BEING NONE, 10 BEING THE WORST IT HAS EVER BEEN. YOU CAN DO IT VERBALLY OR SQUEEZE A BALL. BUT IT IS VERY SUBJECTIVE, AND THAT IN ITSELF HAS SLOWED THE DEVELOPMENT OF MEDICATIONS BECAUSE YOU CANNOT NECESSARILY PREDICT THE EXTENT TO WHICH THESE SUBJECTIVE MARKERS WILL DETERMINE IF A MOLECULE HAS ANALGESIC PROPERTIES OR NOT. ALSO THESE SUBJECTIVE MARKERS DO NOT GIVE US AN UNDERSTANDING OF ABOUT THE CHARACTERISTICS OF THE PATIENTS, NOR DO YOU KNOW NOR CAN YOU DETERMINE WHETHER A PARTICULAR INDIVIDUAL MAY BE MA LIN DPERRING OR NOT. SO THERE IS A NEED OF BIOMARKSERS FOR DEVELOPMENT FOR ACCELERATING DEVELOPMENT OF MEDICATIONS. THE BIOMARKERS TO HELP US ADDRESS PERSONALIZED INTERVENTIONS FOR MANAGE. PAIN, AND THEN, OF COURSE, THERE IS A NEED OF BIOMARKERS FOR EVERYDAY CLINICAL PRACTICE. THE USE OF BIOMARKERS IS BASICALLY AGNOSTIC AND IT'S ACTUALLY WHAT OUR OBJECTIVE MARKERS THAT CAN BE DEVELOPED, IT CAN GO FROM IMAGING TO PHENOTYPIC CHARACTERIZATION TO OMICS. THE STUDY WILL AIM TO DO THAT, IT WILL TAKE ADVANTAGE OF ONE OF THE TWO CLINICAL TRIAL NETWORKS THAT NINDS IS PROPOSING IN ORDER TO BE ABLE TO ADVANCE RESEARCH INCLUDING DATA BIOMARKERS BUT NOTHER ONE IN ORDER TO ACCELERATE -- WHICH YOU CAN ACTUALLY DO FACE TREAT CLINICAL TRIALS. SO THIS IS THE THIRD MAJOR INITIATIVE, HERE IT IS, CLINICAL TRIAL TO IMPROVE QUALITY, EFFICIENCY,, THIS WILL ALLOW FOR A NETWORK FOR INVESTIGATING THE VALUE OF ANALGESICS FOR RARE PAIN CONDITIONS AS WELL AS FREQUENT PAIN CONDITIONS, BUT RARE PAIN CONDITIONS WAS IDENTIFIED AS STRATEGY BY THE FDA THAT MAY ACCELERATE AND BRIQING INVESTIGATIONS TO THE CLINIC IN THAT IF YOU AIM A MEDICATION FOR A RARE CONDITION, IF IT HAS SIDE EFFECTS, IT IS NOT AS IMPACTFUL AS IF YOU HAVE MEDICATION THAT WILL GIVEN TO MANY, MANY PEOPLE. SO THEY WANT TO CREATE A CLINICAL TRIAL NETWORK THAT WILL ALLOW TO RECRUIT THOSE PATIENTS IN A TIMELY MANNER. THE OTHER CLINICAL TRIAL WILL BE MORE ENGAGED ON PHASE 2 CLINICAL TRIALS AND WILL BE UTILIZED, BOTH OF THEM, FOR THE DEVELOPMENT OF BIOMARKERS. SO THIS IS WHERE WE ARE WITH THE HEAL INITIATIVE AND THE OPIOID CRISIS AND YOU WILL BE HEARING CONSTANTLY FROM US BECAUSE WE ARE AT THE END OF 2018 FISCAL YEAR BUT NOW WE HAVE TO GEAR OURSELF TO LAUNCH THE INITIATIVES FROM 2019. AGAIN I'M GOING TO HIGHLIGHT THE MONEY WE GOT FOR 2018 CAN BE SPENT IN 2018 AND 2019, BUT WE NOW ARE GOING TO BE GETTING US TO BASICALLY DEPLOY NEW PROJECTS AS PART OF HEAL. THOSE PROJECTS AGAIN HAD TO GO THROUGH THE DIRECTOR'S OFFICE FOR FOR APPROVAL BY DIFFERENT INSTITUTES. THE MOMENT THEY GET APPROVED, WE'LL MAKE YOU AWARE OF IT, OF COURSE. THE OTHER COMPONENT I DO WANT TO HIGHLIGHT BECAUSE CERTAINLY OUR FUNDING FOR HIV HAS BEEN GOING DOWN AS A RESULT OF THE REORGANIZATION OF WHAT THE PRIORITIES OF THE NIH ARE OF THE HIV, A SIGNIFICANT PORTION OF OUR BUDGET IS ACTUALLY A LITTLE BIT MORE THAN -- 25% GOES TO HIV RESEARCH. AND THIS IS EXTREMELY RELEVANT BECAUSE OBVIOUSLY DRUG USE, MOST NOTABLY INJECTION JUG DRUG USE IS ASSOCIATED WITH INFECTIVITY BUT ALSO USAGE OF DRUGS IS ASSOCIATED WITH VERY NEGATIVE OUTCOMES IN PATIENTS THAT HAVE AN HIV-POSITIVE. SO I WANT TO HIGHLIGHT A STUDY, IT ALSO BRINGS FORWARD THE UNIQUENESS AND HOW SOMETIMES ALL ISSUES ARE ARTIFICIAL. WE'VE SPOKEN A LOT ABOUT THE OVERDOSES AND THE CONSEQUENCES OF THE CRISIS. BUT THERE THE CONSEQUENCES WAS FELT IN INDIANA WITH THESE VERY FAST INFECTION AMONG -- WITH HIV IN A VERY SMALL COMMUNITY IN INDIANA, SCOTT COUNTY, DUE TO THE FACT THAT THEY WERE INJECTING WITH CONTAMINATED MATERIALS, AND THE INFECTIVITY HAPPENED VERY, VERY RAPIDLY. WE'RE SEEING NOW THAT WITH WITH HEPATITIS C WE DON'T SPEAK MUCH ABOUT IT BUT THE INCIDENT DENS RATE IS GOING SIGNIFICANTLY UP AND EACH THOUGH WE HAVE CURES FOR HEPATITIS C, PATIENTS THAT HAVE A SUBSTANCE USE DISORDER AND VERY MUCH -- MOST OF THEM BEING AN OPIOID USE DISORDER, ARE NOT BEING GIVEN ACCESS TO THESE MEDICATIONS. SO EVEN THOUGH THERE ARE CURES, IT'S COST DOES NOT BENEFIT PATIENTS WITH HEPATITIS C CONSEQUENCES ARE -- WORSE, NUMBER ONE, AND SECOND THAT THEY INFECT OTHERS IF THE SOURCE IS NOT UNDER CONTROL. THE PAPER PUBLISHED THIS YEAR ILLUSTRATES HOW IMPORTANT IT IS TO ADDRESS THE CO-MORBIDITY OF THE OPIOID USE DISORDER WITH THE TREATMENT, WITH THE ANTIRETROVIRAL FOR HIV. IN THIS CASE IT'S EXTENDED RELEASE NALTREXONE, YOU CAN SEE THOSE AT BASELINE VERSUS IN THE FOLLOW-UP. YOU CAN CLEARLY SEE WHEN YOU DO THE EXTENDED RELEASAL TREX ZONE A -- VIREMIA. AGAIN THIS ILLUSTRATES WHAT WE'VE ALREADY KNOWN ALL ALONG FOR BUPRENORPHINE AND METHADONE, THAT YOUR OUTCOMES WHERE YOU HAVE HIV-POSITIVE ARE MUCH BETTER IF YOU ARE ON TREATMENT THAT YOU ARE NOT ON TREATMENT. BUT I DO WANT TO HIGHLIGHT THIS PARTICULAR ONE BECAUSE NALTREXONE IS AN AN ANTAGONIST, AND IT CAN ALTER THE IMMUNE RESPONSES AND NEGATIVELY EFFECT THE FUNCTION OF GLIAL CELLS IN THEIR INTERACTION WITH NEURONS, SO IT BEHOOVES US TOO -- SOMEONE THAT IS HIV-POSITIVE OF RECEIVING AN OPIOID ANTAGONIST TREATMENT AS OPPOSED TO AN AGONIST -- LIKE BUPRENORPHINE. THESE ARE THREE DIFFERENT DRUGS WITH VERY DISTINCT PHARMACOLOGICAL EFFECTS. AS OF NOW, I DO NOT KNOW OF ANY STUDY THAT HAS ACTUALLY EVALUATED WHETHER THERE ARE DIFFERENCES IN TERMS OF HIV OUTCOMES RELATED TO THE MEDICATIONS WITH THE THREE DIFFERENT CLASSES. I THINK THIS STUDY BRINGS THE QUESTION TO LIGHT THAT THIS IS ACTUALLY SOMETHING THAT WE SHOULD EVALUATE AT GREATER DEATH. DEPTH. THEN THE FINAL TWO SLIDES I WANTED TO ACTUALLY ADVERTISE AND ACTUALLY TWO EVENTS THAT WE'RE ALWAYS VERY PROUD, ONE OF THEM IS THE INTEL INTERNATIONAL SCIENCE AND ENGINEERING FOR ADDICTION SCIENCE AWARD THAT WAS INITIATED BY CAROL KRAUSE AS OUR INSTITUTE 10 YEARS AGO AS PART OF -- AND JACK STEIN HAS BEEN VERY, VERY SUPPORTIVE, WHERE WE ACTUALLY GIVE PRIZES IN THE INTEL FAIR TO HIGH SCHOOL OPPORTUNITIES THAT ACTUALLY HAVE A PROJECT THAT RELATES TO SAN BERNARDINO STANCE TO A SUBSTANCE USE DISORDER, IN COLLABORATION IN PARTNERSHIPS WITH NIDA, BUT ACTUALLY -- IT'S ALWAYS INCREDIBLE TO HEAR THESE YOUNG PEOPLE BECAUSE IT REMINDS US OF CREATIVITY AND INNOVATION AND THE POWER OF SCIENCE AND CURIOSITY. SO THIRD PRIZE WAS SAADH AHMED, FROM GEORGIA, HE GOT THE THIRD AWARD FOR DEVELOPMENT OF A DRUG LIKENESS RULE FOR NATURAL PRODUCTS. SO WE OF COURSE TRYING TO IDENTIFY WHICH CHARACTERISTICS OF A CHEMICAL IS LIKELY TO BE A GOOD MEDICINE, BUT SUCH A STORY HAS NOT BEEN DONE FOR NATURAL PRODUCTS, SO USING SIMILAR TYPES OF ALGORITHM, HE DEVELOPS A NEW ALGORITHM THAT MAXIMIZES THE LIKELIHOOD OF NATURAL PRODUCTS MAY HAVE MEDICINAL PROPERTIES, EXTREMELY KREE ATI. THE SECOND ONE CAME TO THREE FROM AMERICAN HIGH SCHOOL IN FREMONT, CALIFORNIA, THEY DEVELOPED A LABTRACK, A MICRO-TELEMETRY DEVICE FOR MODELING MICE BEHAVIOR. YOU CAN SAY WELL, THERE ARE ALREADY MANY CAGES THAT MONITOR BEHAVIOR IN MICE. THIS IS A NANOTRIP YOU PUT IN THE LITTLE NANOCHIP YOU PUT IN THE LITTLE CREATURE. IT APPEARS TO BE MUCH LESS COMPLICATED MECHANISMS THAN THE ONE THAT ARE CURRENTLY AVAILABLE. THEN THE FINAL, THE FIRST PRIZE WENT TO TWO HIGH SCHOOL STUDENTS FROM SALT LAKE CITY TRYING TO DETERMINE ONE OF THE BIG CHALLENGES ON DETECTED SUICIDE. CLASSIFICATION OF UNDETERMINED DRUG-RELATED DEATHS USING MACHINE LEARNING TECHNIQUES. I MEAN, SO WE HAVE ALL OF THESE HOAFER DOSES AND IN MANY CASES WE DON'T KNOW WHAT PERCENTAGE OF OVERDOSES ARE ACTUALLY PURSUANT IT TO SUICIDE VERSES THOSE WHO ARE NOT. IT'S IMPORTANT TO RECOGNIZE BECAUSE ULTIMATELY INTERVENTIONS TO PREVENT OVERDOSES ARE GOING TO HAVE TO TAILOR DOSE CIRCUMSTANCES WHERE THERE WAS SUE SUICIDAL INTENT. SO TAKING DATA INFORMATION THAT ACTUALLY WAS CLEAR THAT A PATIENT HAD DIED FROM A SUICIDE THAT TOOK THOSE INDICATORS AND APPLIED IT TO TWO DIFFERENT DATABASES TO ACTUALLY IDENTIFY WHERE THEY KNEW ACTUALLY WHERE IT WAS, WHERE IT WAS NOT, WHETHER THEY COULD EXTRACT THOSE THAT HAVE COMMITTED SUICIDE. IN FACT THEIR ALGORITHM WAS QUITE GOOD. I THINK ABOUT THIS TYPE OF STRATEGY TO APPLY IT, OF COURSE, NOT WHEN YOU ALREADY HAVE DIED BUT HOW WE COULD USE THESE INFORMATION TOOLS TO PREDIECT PREDICT WHO MAY BE AT HIGHER RISK OF SUICIDALITY. SO IT WAS VERY EXCITING TO SEE IT, IT'S ALWAYS EXCITING TO SEE THE PARENTS HOW PROUD THEY ARE, SOMETIMES THEY BRING THE TEACHERS, THEN THEY GO TO OUR INTRAMURAL PROGRAM AT THE CLINICAL CENTER AND THEY ALSO GO TO BALTIMORE AND WE TRY TO HELP THEM NETWORK SO THAT IF IN THE FUTURE THEY WANT TO DO RESEARCH, WE CAN FACILITATE THAT. AND THEN THE FINAL SLIDE I HAVE FOR TODAY IS AN ADVERTISEMENT FROM OUR FRONTIERS IN ADDICTION RESEARCH THAT IS THE SYMPOSIUM THAT'S BASICALLY DONE AS A SATELLITE THE DAY BEFORE WE INITIATE THE SOCIETY OF NEUROSCIENCE. IT'S LED BY THE DIVISION OF BASIC NEUROSCIENCE, AND WE'VE BEEN DOING IT FOR THE PAST THREE IN PARTNERSHIP WITH THE -- WE ALWAYS HIGHLIGHT AREAS WHERE WE ACTUALLY ENCOURAGE RESEARCHERS TO COME IN TO THE SPACE TO EXPLORE OUR DATA SIGH EN, NUMBER ONE. NUMBER TWO, EFFECTS OF EARLY LIFE ADVERSITY ON SUBSTANCE USE DISORDER-RELATED CIRCLE TRY, AND THE THIRD ONE, NOVEL OIP YOID RECEPTOR SIGNALING IN ADDICTION AND PAIN. IN GENERAL, RECEPTOR SIGNALING IS EXTREMELY IMPORTANT FOR EVERYTHING THAT RELATES TO GPCRs, VERY RELEVANT TO NEUROSCIENCE, INCREDIBLY RELEVANT FOR WHAT WE'RE LIVING ON WITH OPIOIDS AS ADDICTIVE DRUGS. WHO HAS WON, I DON'T KNOW YET BUT IT WILL BE ANNOUNCED AT THIS TIME. AGAIN I WANT TO THANK YOU ALL FOR YOUR ATTENTION BUT I ALSO WANT YOU TO MAKE AWARE, I STAND UP AND I SPEAK BUT BEHIND ALL OF THIS PRESENTATION, ALL OF THIS CONCEPT IS THE WORK OF NIDA STAFF WHICH HAS BASICALLY -- IS INCREDIBLE, THEY DON'T STOP TO SURPRISE ME, AND IT'S BASICALLY WHAT KEEPS ME AWAKE AT NIGHT IS WILL I BURN THEM OUT. AND IT IS, BECAUSE IT'S ACTUALLY -- IT'S THIS CONSTANT, CONSTANT NEED TO ACTUALLY KEEP ON OUR TOES BECAUSE THINGS ARE MOVING SO RAPIDLY. WHAT WE'RE LIVING IS A TRAGEDY, IT'S A TERRIBLE TRAGEDY, BUT WE ARE ALSO IN A UNIQUE POSITION, AND THAT ALSO INCLUDES NOT JUST NIDA BUT ALL OF YOU AS SCIENTIST SCIENTISTS TO REALLY MAKE A DIFFERENCE TO CHANGE IT, AND THIS IS OUR ABILITY TO COORDINATE OUR EFFORTS WITHIN NIDA, OUTSIDE NIDA, THAT ULTIMATELY CAN GET THIS THING UNDER CONTROL. AND IT IS THAT COMMITMENT THAT WE CAN DO IT THAT ULTIMATELY WILL LEAD US TO ACTUALLY SHOW THAT ADDICTION HAS HORRIFIC DEVASTATING CONSEQUENCES, BUT IT CAN BE PREVENTED AND TREATED. WHEN WE HAVE KNOWLEDGE, WE CAN ACTUALLY OF COURSE IMPROVE, BUT IN THE MEANTIME, WE ALSO HAVE TO RECOGNIZE THAT, AND WE HAVE TO EDUCATE OUR SOCIETY SO THIS FACILITATES THE ABILITY TO PREVENT NOT JUST THOSE WITH OPIOID USE DISORDER, SUBSTANCE ABUSE DISORDER IN GENERAL. THANKS VERY MUCH FOR YOUR ATTENTION. [APPLAUSE] I THINK WE HAVE TIME FOR QUESTIONS. >> THANK YOU AS ALWAYS, NORA, FOR A COMPREHENSIVE AND THOUGHTFUL AND THOUGHT-PROVOKING PRESENTATION. I JUST WANT TO TAKE THIS OPPORTUNITY SINCE I'M ROLLING OFF THE COUNCIL TO THANK YOU, NORA, AND ALL OF THE NIDA STAFF FOR THE INCREDIBLE WORK THAT YOU DO. WE DON'T OFTEN GET TO INTERACT AS COUNCILMEMBERS WITH ALL THE BUT IT'S REALLY IMPORTANT THAT YOU KNOW HOW MUCH WE APPRECIATE HOW YOU TOIL, PARTICULARLY IN VERY CHALLENGING CIRCUMSTANCES. THEY ALWAYS ARE, AS FEDERAL EMPLOYEES AND AS CIVIL SERVANTS, BUT THEY'RE PARTICULARLY CHALLENGING NOW WITH BOTH BUDGET AND POLICY ISSUES, OF WHICH WE ARE ALL QUITE AWARE, AND AS NORA MENTIONED, YOU HAVE A CHALLENGE AND AN OPPORTUNITY AT THE SAME TIME WITH THIS OPIOID EPIDEMIC, SO I KNOW YOU'RE ALL WORKING DOUBLELY AND TRIPLY HARD SO I WANT TO EXTEND MY APPRECIATION FOR ALL THE WORK YOU DO. ONE QUESTION FOR NORA. PERHAPS I MISSED THIS, BUT IN THE HEAL FOUR PROJECT AREAS, TO WHAT EXTENT IS ANY OR ALL OF THEM INTERSECTING THE OPIOID USE DISORDERS WITH INFECTIOUS DISORDERS AND MENTAL HEALTH LIKE SUICIDALITY, ARE THOSE INITIATIVES ABLE TO ADDRESS THINGS BEYOND JUST OPIOID USE DISORDERS? >> INDEED, AND IT BEHOOVES US TO ACTUALLY MAKE THEM PART OF THE WHOLE PACKAGE, EVEN THOUGH THERE'S BEEN MAIN FOCUS IN DECREASE IN OVERDOSE FATALITIES, WE WANT TO EMBED AS OUTCOMES THAT WILL DECREASE -- AND IMPROVE OUTCOMES IN GENERAL IN MEDICAL CARE. SO FOR EXAMPLE IN THE HEALING COMMUNITY STUDIES, WE ARE REQUESTING GOING TO BE EVALUATING, TAKING ADVANTAGE OF THAT INTEGRATED -- TO EXPAND INTERVENTION FOR OPIOID USE DISORDER TO SEE HOW THAT ULTIMATELY IMPROVES OUTCOMES AND HOW IT MAY AFFECT THE INCIDENCE OF HEPATITIS C IN THE CLINICAL TRIAL NETWORKS, AGAIN, THE PROJECTS, ONE OF THE PARAMETERS THAT ARE BEING MEASURED IS UL MATTLY MEDICAL HEALTH OUTCOMES THAT INTERWE'VES VERY CLOSELY WITH INFECTIOUS DISEASES. AMONG THE MEDICAL MODELS THAT WE'RE TILE TEULLY VERY INTERESTED IN I WAS SPEAKING ABOUT PRIMARY CARE, BUT GENERATING NEW WAYS FOR SPECIALTY MEDICAL PRACTICE TO ACTUALLY BE ACTIVELY ENGAGED IN GIVING AND PROVIDING MEDICATION FOR OPIOID USE DISORDER, AND I THINK THAT ACTUALLY CARLOS HAS BEEN ONE OF OUR GRANTEES IN THAT SPACE, HOW DO YOU MAKE IT HAPPEN, WHAT LEVEL OF SUPPORT TRAINING DO YOU REQUIRE. IMPORTANTLY, HOW DO WE BRING THESE COMPONENTS OF ENGAGEMENT -- I MEAN INTERCEDING OF ADDICTION WITH INFECTIOUS DISEASES, ALSO VERY DIFFICULT AND HARD TO REACH POPULATIONS SUCH AS RURAL COMMUNITIES OR AMERICAN INDIAN COMMUNITIES WHERE THE RATE OF INFECTIONS ARE HIGHER, SO THIS IS, AGAIN, WE HOPE THE HEAL COMMUNITY, WHETHER IT IS THROUGH HEAL COMMUNITY OR THE C TN OR ALSO, TOO, THROUGH MEDICATION DEVELOPMENTS THAT -- I WAS MENTIONING IT WITH EXTENDED RELEASE NALTREXONE, UNIQUE ADVANTAGES FOR MANAGING PATIENTS THAT ARE ON ANTIRETROVIRAL TREATMENT. IT'S ACTUALLY A DEFAULT COMPONENT OF WHAT WE DO. EVEN IF IT'S NOT EXPLICITLY STATED AS THE MAIN OUT COME, THE MAIN OUT COME AS WE HAVE TO DESCRIBE IT ALL ALONG IS DECREASE THE OVERDOSE FATALITIES, AND TO YOUR LAST POINT ON SUICIDALITY, YES, THIS IS SOMETHING THAT WE ARE EXTREMELY INTERESTED. THROUGH THE EMERGENCY DEPARTMENTS, HOW DO YOU ASSESS SUICIDALITY -- THAT IS ONE OF THE PROJECTS WE WOULD LIKE TO SEE HOW ONE COULD ACTUALLY DEPLOY THE SCREENING AND WHAT WOULD BE THE BLOCKS AND WHAT WOULD YOU DO IF IT'S A POSSIBLE SCREENING, SO THIS IS A COMPONENT THAT WE'RE VERY, VERY INTERESTED, NIMH AND WE AND NIGH PUT IN A PROPOSAL TO TRY TO ADDRESS THESE COMORBIDITIES. >> HI. AS ALWAYS, I MEAN, I THINK I COME AWAY WITH AS MANY QUESTIONS AS I DO NEW INFORMATION. I REALLY APPRECIATE IT. TWO THINGS. ONE, THE REVERSAL DRUGS THAT ARE AVAILABLE, JUST UNDERSCORING HOW IMPORTANT FROM OUR PERSPECTIVE, GROUP THAT I'M WORKING WITH RIGHT NOW, FOUNDATION, FAMILY GROUP, WHERE THAT EXTRA ACTIVITY, INCREASING THE ACTIVITY PERIOD FOR AS MUCH AS TWO MONTHS, BECAUSE HOW MANY PEOPLE LEAVE THE EMERGENCY DEPARTMENT AND REALLY WITHIN THAT PERIOD AND MAYBE SUICIDALITY IS PART OF IT, I DON'T KNOW, BUT THEY OVERDOSE AGAIN AND ULTIMATELY DIE. SO KNOWING THAT THERE'S THAT -- LEAVING THAT WINDOW OPEN FOR TWO MONTHS IS A REAL GIFT, SO JUST UNDERSCORING HOW IMPORTANT THAT IS. THEN THE OTHER THING, AND SOMEWHAT RELATED TO IT IS THE WORK ON MARIJUANA AND CANNABIS. MY CONCERN ABOUT HOW THE PUBLIC VIEWS IT BECAUSE THE HISTORY OF MEDICAL MARIJUANA AND EVEN THAT TERM, I THINK I STRUGGLE WITH SUSPICION AROUND IT. I DON'T TRUST -- I DON'T HAVE A BIG TRUST LEVEL FOR WHAT COMES OUT BECAUSE I THINK IT'S BEEN MISREPRESENTED FOR SO LONG, AND IF THERE'S INCREASED USAGE, DOES THAT CREATE MORE ISOLATION WITHIN THE PERSON'S LIFE? DEPRESSION, AGAIN, THAT SORT OF DOWNHILL SPIRAL. AND I DON'T KNOW WHERE THE SCIENCE IS ON THAT, OR WHAT WE COULD EVEN TALK ABOUT IN TERMS OF WHAT WE KNOW AND DON'T KNOW, BUT I THINK IT'S MORE THAN JUST THE CHEMISTRY, THINK IT'S JUST THE PERCEPTION OF THE TRUST THAT PEOPLE HAVE IN THAT BIG CONVERSATION. OFTENTIMES WHEN SOMEBODY TALKS ABOUT LEGALIZING MEDICAL PAIR MA WANNA, THERE'S A MARIJUANA, PLEAS THERE'S A GRIN. WHAT OTHER DRUG TO WE TALK ABOUT THAT WE DISCUSS IN THOSE SAIMS TERMS? SO I'M PUTTING THAT AS A CHALLENGE. >> THERE'S UNFORTUNATELY VERY LITTLE RESEARCH AND AGAIN, THIS IS AN AREA THAT WE RECOGNIZE IT IS IMPORTANT TO ACTUALLY LOOK INTO BECAUSE PATIENTS ARE TAKING THIS MARIJUANA WITH THE BELIEF THAT IT'S MEDICALLY BENEFICIAL AND WE OWE THEM EVIDENCE SO THEY CAN GO WITH KNOWLEDGE OF WHETHER SOMETHING HAS POTENTIAL NEGATIVE EFFECTS. >> THINK THE OTHER ISSUE IS A CREDIBILITY ONE IN THAT THE GOVERNMENT DOES NOT HAVE A LOT OF CREDIBILITY WHEN WE TALK ABOUT MARIJUANA. UNFORTUNATE LIT INDUSTRY IS NOT LOOKED AT THE SAME WAY THE TOBACCO INDUSTRY IS, SO A LOT OF THE MESSAGES THAT ARE COMING OUT ARE NOT THE BEING VIEWED, PUBLIC HEALTH MESSAGES ARE NOT BEING VIEWED AS SERIOUSLY AS MEMBERS OF THE JURY MESOPOTAMIAAGES THAT SERIOUSLY AS MESSAGES DEALING WITH LEGALIZATION. >> I WANT TO COMMEND YOU FOR YOUR PRESENTATION, OF COURSE STAFF FOR COMING UP WITH THE VARIOUS IDEAS. PARTICULARLY WANT TO ACKNOWLEDGE YOUR FOCUS ON PAIN, THE JUSTICE JUSTICE -- >> THIS CONFERENCE APPEARS TO BE INACTIVE AND WILL END SOON. IF YOU'RE THE HOST AND WISH THIS CONFERENCE TO CONTINUE, PLEASE PRESS ANY KEY ON YOUR TELEPHONE TOUCH PAD. >> WHOEVER THAT PERSON IS -- [LAUGHTER] >> ALL RIGHT. TECHNOLOGY NOT WITHSTANDING, PAIN -- THE JUSTICE SYSTEM AND MEDICATIONS. WHAT YOU'RE SHOWING IN YOUR SPECTRUM OF ACTIVITIES IS THIS IS A VERY PLEX ISSUE. THERE IS THIS VIEW THAT ADDICTIVE MEDICINE IS SIMPLE, IT'S A REDUCTIONIST VIEW. IN YOUR BLOG, YOU CITE SARAH WICKMAN'S VIEW THAT EIGHT HOURS OF TRAINING IS TOO MUCH FOR PRIMARY CARE TO DEAL WITH ADDICTION, THAT BASICALLY PRACTITIONERS SHOULD JUST BE ABLE TO HAND OUT MED KAITIONS WILLY-NILLY WITHOUT ANY CONSEQUENCES FOR WHAT THEY'RE DOING, ANY KNOWLEDGE ABOUT WHAT THEY'RE TREATING, AND LATER IN YOUR BLOG, YOU POINT OUT THAT THERE ARE THOSE WHO FEEL THAT THEY'RE NOT GETTING ADEQUATE TRAINING. SO EIGHT HOURS OF TRAINING UNDER DATE OF 2000 IS IN MY MIND VERY DE MINIMUS, AS I'VE POINTED OUT TO OTHERS. I'M RENEWING MY LICENSES, I HAVE TO DO 50 HOURS OF CONTINUING EDUCATION EVERY TWO YEARS, SO I CAN'T UNDERSTAND WHY EIGHT HOURS OF TRAINING IN AN AREA WITH WHICH I HAVE LITTLE FAMILIARITY IS TOO MUCH WHEN MY MEDICAL BOARDS ARE REQUIRING ME TO DO 50 HOURS EVERY TWO YEARS JUST TO MAINTAIN MY LICENSE, AND IF YOUR NUMBER COMES UP AND YOU CAN'T DOCUMENT THAT 50 HOURS, YOU LOSE YOUR LICENSE. SO WHAT'S HAPPENING IS THAT PEOPLE ARE VIEWING ADDICTION MEDICINE, ADDICTION ACTIVITY AS SIMPLISTIC, I LIKE THE NOTION OF INTEGRATED CARE WHERE YOU BRIQ THE SCIENCE, THIS IS WHAT YOU'RE DOING, TO INFECTIOUS DISEASE AND OTHER COMORBIDITIES. WE'RE GOING TO HAVE TO DEAL WITH THE ISSUE OF STIGMA AND DISCRIMINATION AS A PART OF THE CONSTRUCT. THAT IS MISSING FROM THIS DISCUSSION, PARTICULARLY IN THE JUST TI ARENA, WHERE YOU HAVE IN SOME CASES ABUSES OF THE EXERCISE OF DISCRETION IN DECIDING WHO HAS A PROBLEM, WHO DOESN'T HAVE A PROBLEM. I'M DOING A PRESENTATION IN NEW ORLEANS IN BATON ROUGE NEXT WEEK AND I WAS LOOKING AT WHO GETS ARRESTED FOR WHAT SUBSTANCES AND IT TURNS OUT POOR PEOPLE AN AFRICAN-AMERICAN PEOPLE GET ARRESTED FOR MARIJUANA USE WHEREAS WHITE PEOPLE DON'T AND GUESS WHO USES MORE MARIJUANA? WHITE PEOPLE, ACCORDING TO THEIR OWN DATA. SO WE HAVE TO DEAL WITH THIS ABUSE OF EXERCISE OF DISCRETION IF WE'RE GOING TO DEAL WITH SOME OF THESE ISSUES, AND HOPEFULLY YOUR WORK WITH THE CRIMINAL JUSTICE SYSTEM CAN HELP FACILITATE THAT BECAUSE IT INTERFERES WITH PEOPLE'S VIEW OF WHAT THE REAL AGENDA IS WHEN IN FACT RACE, ETHNICITY AND POVERTY BECOME CHARACTERISTICS OF THE DECISION-MAKING PROCESS RATHER THAN WHAT'S GOING ON PSYCHOLOGICALLY AND FISCALLY AND ECONOMICALLY. SO AS YOUR STAFF, BUDGET NOTWITH STANDING AND TOO MUCH WORK NOT WITHSTANDING WORKING WITH THE JUSTICE COMMUNITY, HOPEFULLY YOU'LL LOOK AT THESE ISSUES THAT UNDERMINE OUR ABILITY TO HAVE AN IMPACT. AS SUSAN POINTED OUT, IF WE DON'T DO THAT, THEN THE TRUST FOR THE PUBLIC HEALTH SYSTEM IS UNDERMINED. WHEN PUBLIC HEALTH TAKES A VERY ANTICOMMUNITY PERSPECTIVE, I.E., IGNORES WHAT'S ACTUALLY GOING ON IN THE COMMUNITY, THEN PUBLIC HEALTH HAS NO LEGITIMACY, AND IF PUBLIC HEALTH HAS NO LEGITIMACY, ALL OF WHAT WE DO GETS EVISCERATED AND WEAK ENDED, SO I WANT TO COMMEND YOU AGAIN, YOUR FASTIDIOUSNESS WITH A BROAD SPECTRUM OF ISSUES AND JUST WANTED TO INTRODUCE THESE THEMES SINCE WE WON'T BE HAVING ANOTHER MEETING THIS YEAR. >> THANKS A LOT. AND WE ARE VERY MUCH SENSITIVE TO THE ISSUE OF GETTING A BETTER UNDERSTANDING ABOUT FIRST OF ALL WHAT ARE THE PRACTICES AND WHAT ARE THE ROAD BLOCKS THAT ACTUALLY RESULT ON THE WAY THAT INDIVIDUALS END UP IN JAIL OR PRISON AS IT RELATES TO SUBSTANCE USE DISORDER AND GET ACCESS TO MEDICATION. THIS IS WHY WE ARE STARTING BY LAUNCHING FAIRLY LARGE SUR FAYS TO GET AN FAY VAIS SURVEYS TO GET AN IDEA OF THE CHALLENGES THAT WE HAVE. YOU'RE ABSOLUTELY RIGHT, THERE IS STIGMATIZATION IN THE JUSTICE SETTING IS MUCH MORE PREVALENT THAN IN THE HEALTHCARE SYSTEMS, SO HOW DO YOU FIRST OF ALL FIND OUT AND HOW DO YOU CHANGE THAT SYSTEM. THAT IS WHAT WE HAVE IN OUR HANDS AS A CHALLENGE. WHAT I WOULD LIKE TO DO, TAKE ADVANTAGE OF THE HEALING COMMUNITIES BY MAKING ACTIVE AND ENSURING THAT AS MANY OF THE PRISONS OR JAILS ARE GIVEN MEDICATION-ASSISTED THERAPY AS WE CAN OF THE THREE STATES THAT ARE GOING TO BE SELECTED THAT WE CAN CLEARLY SEE HOW THAT SIGNIFICANTLY IMPACTS ON THE OUTCOMES. SO IF WE CAN SHOW THAT, THEN HOPEFULLY OTHERS WILL THEN GET INSPIRED TO DO THE SAME. THAT'S THE PURPOSE BUT IT IS A CHALLENGE BECAUSE IT'S HETEROGENEOUS AND IT HAS A STRONG TRADITION, IT'S DIFFERENT THAN ACADEMIC CENTERS AND HEALTHCARE. >> AND DON'T FORGET COST AND REIMBURSEMENT, HOW WE PAY FOR SOME OF THESE SERVICES, WOOR AT A WE'RE AT A DELICATE TIME PERIOD WITH REGARD TO HOW YOU -- IF PEOPLE CAN'T GET PAID, THOSE MODELS AREN'T USED. >> WE ARE VERY AWARE, AND IN FACT, BOTH JCOIN AND THE HEALING COMMUNITIES ARE GOING TO HAVE AN ECONOMIC ANALYSIS IN THEM BECAUSE THE IDEA IS WE ACTUALLY WANT TO DO -- EVIDENCE WHEN IT'S INTERVENTIONS THAT ARE SUSTAINABLE OTHERWISE IT'S A THEORETICAL EXERCISE. >> THANK YOU VERY MUCH FOR YOUR PRESENTATION AND ALSO TO THE DIVISION DIRECTORS FOR PRESENTATIONS THIS MORNING. IT'S ALWAYS REMARKABLE TO SEE THE BREADTH OF ACTIVITY AT NIDA, PARTICULARLY NOW WITH THIS DRAMATIC SURGE IN ACTIVITY A AND I JUST WANT TO UNDERSCORE JUDY'S POINT OF A BIG DEEP THANKS TO THIS GROUP IN THIS ROOM FOR ALL THE INCREDIBLE WORK, AND IT'S GREAT TO SEE THAT THERE'S BEEN APPROVAL FOR SOME INCREASE IN STAFFING, WE HEARD ABOUT SOME OF THAT TODAY, BUT I JUST WANT TO UNDERSCORE THE IMPORTANCE OF THE STAFFING INFRASTRUCTURE HERE TO ACCOMMODATE THIS SPIKE IN ACTIVITY. TWO QUESTIONS REGARDING THE HEAL INITIATIVE, ONE IS WHAT THOUGHTS OF SPECIFIC INITIATIVES IN HEAL. IT'S GREAT THE TO HEAR ABOUT THE ABCD, REALLY A REMARKABLE PROJECT, BUT IN THE CONTEXT OF HEAL, ARE THERE SOME PLANS AROUND YOUTH ACTIVITIES? AND THE SECOND QUESTION IS, CAN YOU TALK A LITTLE BIT ABOUT THE EXPECTED DURATION OF THE SUMMIT MENTAL HEAL FUNDING SUPPLEMENTAL HEAL FUNDING AND ABOUT NEW INITIATIVES THAT MIGHT BE LAUNCHING, AND WHAT HAPPENS TO THEM IF THE FUNDING ENDS IN A FEW YEARS, LIKE FOR EXAMPLE, THESE CLINICAL RESEARCH CENTERS, SHOULD WE BE HAVING A DIALOGUE AROUND PROTECTING -- JUST LIKE WE DID WITH LONG-STANDING SORT OF DOLLARS DEDICATED TO HIV/AIDS RESEARCH, SHOULD WE BE THINKING ABOUT IN THE CONTEXT OF HEAL A SIMILAR KIND OF MECHANISM TO HAVE DEDICATED FUNDING AS NEEDED TO SOME PERIOD TO SUSTAIN THESE THINGS THAT ARE BEING LAUNCHED IN THE NEXT YEAR OR TWO? >> THE FIRST QUESTION, AS WE'RE COMPETING FOR THE 2,019-DOLLARS, AND AREA WE HIGHLIGHTED, THE WHOLE CONCEPT OF PREVENTION. SO YOU LOOK AT PREVENTION OF OPIOID USE DISORDER, A LOT OF WORK HAS GONE INTO PREVENTION FOR BETTER PRESCRIPTION PRACTICES FOR OPIOIDS, BUT THE EPIDEMIC HAS CHANGED AND NOW WE KNOW A SIGNIFICANT NUMB OFFER OF INDIVIDUALS THAT WILL STARTING TO TAKE HEROIN OR SYNTHETIC OPIOIDS AREN'T NECESSARILY GOING TO PRESCRIPTION OPIOIDS, AND HIGHLIGHTING THE IMPORTANCE OF DOING PREVENTION FOR A SUBSTANCE USE DISORDER. THE OTHER THING ABOUT IT, IF YOU LOOK AT THE DATA WE HAVE FROM SURVEYS, WE SEE THAT ADOLESCENTS HAVE VERY, VERY LOW RATES OF OPIOID USE DISORDER. I MENTIONED THIS IN COUNCIL IN THE PAST. BUT THEN YOU GO 18 TO 25, AND IT JUMPS. SO THAT TRANSITION IS ONE WHERE WE'RE SEEING A VERY SIGNIFICANT UPTICK ON THE OPIOIDS, FROM EX-PAIR MENTATION, THEN YOU SEE IT'S REFLECTED IN THE OVERDOSES IN THAT YOUNG AGE GROUP, WHICH BRINGS TO NOTION, MADE US VERY, VERY AWARE, WHAT ARE THE PREVENTION STRATEGIES THAT ARE NECESSARY TO IMPACT THIS GROUP OF YOUNG PEOPLE AND THE GOOD THING ABOUT ALL OF THIS, WE'RE WORKING VERY HARD, BUT THEY ARE FORCING US TO THINK AND IT'S SORT OF WHAT OUR STRATEGIES, OF COURSE, THROUGH COLLEGE IS ONE AND THE ALCOHOL INSTITUTE AND WE'RE PARTNERING WITH THE ALCOHOL INSTITUTE FOR THAT, IT HAS A LONG TRADITION AND SUCCESS FOR PREVENTION. HEALTHCARE IS ANOTHER ONE WHERE WE CAN ACTUALLY TARGET PREVENTION, BUT WE NEED MODELS. AND FINALLY, WE NEED PREVENTION AND THE JUSTICE SETTING BECAUSE YOU'RE GOING TO GET YOUNG PEOPLE THERE. SO THOSE THREE SPACES ARE THE ONES WE'VE BEEN DISCUSSING BACK AND FORTH FOR OPIOID USE DISORDER WHILE KEEPING ALSO IN MIND THAT THE STUDIES WITH THE ABCD AND TRYING TO EXPAND INTO BABIES AND IS LEARNING -- WILL ALSO BE VERY, VERY RELEVANT, SO WE'RE HIGHLIGHTING THE THIS AS AN AREA OF RESE. VERY IMPORTANT. WITH RESPECT TO HOW LONG IS THE MONEY THAT IS GOING TO BE COMING FOR HEAL FOR THE PROJECTS, SOME OF THE PROJECTS HAVE TIME CONSTRAINTS, FOR EXAMPLE, THE HEALING INITIATIVES WE'RE SAYING THREE OR FOUR YEARS, PERHAPS FIVE. BUT THREE OR FOUR YEARS. WITH THE MEDICATION DEVELOPMENT, THE MONEYS ALLOCATED FOR CERTAIN AMOUNT OF TIME, BUT ONE CAN SEE THAT THE PROJECT ITSELF CAN GO ON IN PERPETUITY IF THERE IS A STRONG PIPELINE AND THERE IS ACTUALLY MERITORIOUS SCIENCE GOING ON. I ACTUALLY DISCUSSED THIS ISSUE WHERE THE MONEY HAS NOT BEEN APPROPRIATED FOR ONE OR TWO YEARS, IT'S JUST BEEN APPROPRIATED TO NIH, SO THE ISSUE IS, WHAT HAPPENS WHEN WE ACTUALLY CONTROL THE OPIOID CRISIS? IT WILL BE FANTASTIC WHEN WE CONTROL THE OPIOID CRISIS AND I HOPE BY THEN, WE DON'T HAVE A MAJOR GROWING -- BECAUSE OF ALL THE NEGATIVE -- THE INCREASED USE AND ABUSE OF CANNABIS, COCAINE, METHAMPHETAMINE, THE INCREASED PROBLEMS WITH ELECTRONIC CIGARETTES, I THINK THAT THE INCREASED PRESENCE OF SYNTHETIC DRUGS ACTUALLY BEING MANUFACTURED WITH EXTREMELY HIGH REWARDING EFFECTS. I WISH I COULD SORT OF SAY I BELIEVE WE WILL OVERCOME ADDICTION. I THINK THAT'S WHAT WE'RE AIMING FOR, BUT IT IS LIKE WITH INFECTIOUS DISEASES. THERE IS ALWAYS AN UNKNOWN OF AN EMERGING TREND THAT WILL HAPPEN. AND SO WE HAVE TO BE AT THE ALERT SO THAT WE CAN USE SCIENCE AS THESE NEW EMERGING TRENDS COME AROUND SO WE CAN DO INTERVENTIONS TO UNDERSTAND THEM AND TO TREAT THEM. THAT REQUIRES RESOURCES. SO I THINK THAT ULTIMATELY HOW THE FUNDING, THAT $500 MILLION, WILL ULTIMATELY BE ALLOCATED BECAUSE IT'S ALL GOING THROUGH THE OFFICE OF THE DIRECTOR FOR ALLOCATION IS NOT COMPLETELY KNOWN RIGHT NOW BUT I CAN TELL YOU THAT EVEN I PREDICT WE'RE GOING TO HAVE THE LINGERING EEIVELGT OF SYNTHETIC OPIATES, PLUS OTHER ASPECTS THAT ARE STARTING TO EMERGE CHALLENGING US AS A FIELD, LIKE FOR EXAMPLE, THE RECOGNITION THAT THERE ARE ADDICTION TO CERTAIN BEHAVIORS LIKE VIDEO GAMING, WE DON'T KNOW WHAT THE FUTURE ACTUALLY -- WHAT THE SURPRISES OF THE FUTURE ARE WITH RESPECT TO ADDICTIVE BEHAVIORS. >> NORA, ALL THESE EXCITING AREAS, IT'S EXCITED TO HE ZOO THE RENEWED INTEREST IN PSYCHIATRIC CO-MORBIDITY AND ADDICTION. I'M WONDERING WHAT YOU'RE THINKING ABOUT HOW TO WORK WITH NIMH, BECAUSE THE CO-MORBIDITY, DEPRESSION, PTSD AND SO FORTH HAS ALWAYS BEEN IN BETWEEN NIDA AND NIMH. I'M WONDERING IF YOU'RE THINKING ABOUT WORKING WITH NIMH TO MOUNT STUDY. >> I THINK IT'S AN OPPORTUNITY. I THINK SOMETIMES CIRCUMSTANCES MAKE IT SO CLEAR YOU CAN NO LONGER IGNORE IT. IN CO-MORBIDITY, WE HAVE HAVE WORKED A LOT WITH SCHIZOPHRENIA AND NICOTINE, BUT I THINK WHAT HAS EMERGED, THERE'S A LOT OF INTEREST IN CANNA BUSINESS IN PTSD, BUT RIGHT THE NOW WHAT'S EXTREMELY WILL IMPORTANT FOR BOTH IS DEPRESSION, AND IN APRIL THEY BROUGHT THE PATIENTS TO THE FDA TO TRY TO FIGURE OUT WHERE RELIABLE INTERVENTION, DEPRESSION WAS ONE OF THEM. THAT'S ONE OF THE FACTORS THAT LEADS TO RELAPSE. SO ALSO THE NEUROBIOLOGY AND THE NEUROCIRCUITRY IS SO INTER -- THAT -- I BASICALLY PREDICT THE DIRECTIONALITIES IN BOTH DIRECTIONS FROM DEPRESSION TO TAKING DRUGS BECAUSE THEY MAKE YOU FEEL BETTER TEMPORARILY TO BEING ADDICTED MAKING YOU FEEL VERY DEPRESSED DURING THE WITHDRAWAL STAGES. SO I THINK THIS IS A VERY, VERY GOOD OPPORTUNITY, VERY IMPORTANT FOR NEUROSCIENCE RESEARCH, SO WE -- ONE OF THE PROJECTS THAT IS BEING DISCUSSED AS I MENTIONED BEFORE IS THAT ONE OF CO-MORBIDITY OF OPIOID USE DISORDER WITH MENTAL ILLNESSES. PARTICULARLY ALSO VERY INTERESTED ON FIGURING OUT THE COMPONENT OF SUICIDALITY AND FIGURE OUT WHAT INTERVENTIONS YOU NEED TO ACTUALLY DO WHEN SOMEONE OVERDOSES THAT HAS SUICIDAL INTENT. YOU CAN HAVE DIFFERENT GRADATIONS, BUT YOU NEED TO ADDRESS IT, AND SO YES, FROM THE BASIC TO THE CLINICAL, TO THE EPIDEMIOLOGICAL, WE NEED MORE INFORMATION. >> I WANT TO THANK YOU FOR THE OPPORTUNITY TO BE A PART OF YOUR COUNCIL. I'M THE NOT SURE WHAT HAPPENED, BUT YOU DID LET A NON-SCIENTIST SERVE, AND IT'S BEEN A PLEASURE TO DO THAT, SO THANK YOU FOR THAT OPPORTUNITY. SECONDLY, I WANT TO THANK YOU FOR YOUR RENEWED EMPHASIS ON PREVENTION. I WOULD SAY IN ALL RESPECT THAT IT HAS BEEN A LITTLE LATE COMING BUT I'VE BEEN VERY APPRECIATIVE TO SEE YOUR LEADERSHIP OVER THE LAST YEAR PARTICULARLY IN PREVENTION BECAUSE IT'S SO CRITICAL THAT, YES, WE NEED NEW MEDICATIONS, YES, WE NEED EFFECTIVE TREATMENT, BUT WE CERTAINLY ARE NEVER GOING TO TREAT OUR WAY OUT OF THIS PROBLEM, SO THANK YOU FOR THAT. ALSO THANK YOU FOR PARTNERING WITH US. WE HAVE, AS DR. JACK STEIN SAID, WE HAVE A NEW PUBLICATION JUST HITTING THE STREET THIS WEEK THAT YOU GUYS HELPED US WRITE AND FUND. TO GIVE OUR MORE THAN 5,000 COALITIONS A HEAD START ON THE SCIENCE AROUND OPIOIDS THAT IS WRITTEN FROM A COMMUNITY PERSPECTIVE AND WE APPRECIATE THAT, AND WE'RE IN THE PROCESS NOW OF WRITING ONE ON ELECTRONIC CIGARETTES, AND I KNOW THE PEOPLE AROUND THIS TABLE UNDERSTAND THAT THAT ISSUE IS REALLY KILLING OUR HIGH SCHOOLS, THIS THINGS CALLED JULING, TEACHERS DON'T KNOW HOW TO MANAGE IT, SO WE APPRECIATE THAT TOO. I WOULD SAY, YOUR LAST COMMENT I THINK IS A VERY APPROPRIATE COMMENT THAT WE DON'T KNOW WHAT THE KNEW TOUR FUTURE HOLDS. CATCA IS NOW ABOUT 26 YEARS OLD BUT GUESS HOW WE WERE CREATED? WE WERE CREATED BECAUSE THERE WAS A CRISIS, IT WAS AN EPIDEMIC, IN THE MID EIGHTIES, THE PRESIDENT HAD A DRUG ADVISORY COUNCIL THAT MET FOR THREE YEARS, PEOPLE LIKE THE ONES IN THIS ROOM, GO BACK 20 OR 25 YEARS AGO, BECAUSE A YOUNG PROMISING BASKETBALL PLAYER FROM THE UNIVERSITY OF M.D. NAMED ELEMENTARY EN BIAS DIED OF AN OVERDOSE, WAS DRAFTED NUMBER ONE IN THE NBA AND NEVER GOT A CHANCE TO PLAY ONE DAY. SO I GUESS MY POINT FOR THAT LONG STORY IS THAT -- AND HERE WE ARE NOW DEALING WITH THE OPIOIDS. BUT WE HAVE TO BE CAREFUL IN THIS ENVIRONMENT TO HAVE EVERYONE UNDERSTAND THAT WE'RE JUST NOT FACING AN OPIOID CRISIS, WE ARE FACING MULTIPLE DRUG CRISIS, COCAINE IS ON THE RISE AGAIN, METH IS ON THE RISE AGAIN, OBVIOUSLY WE'RE DEALING WITH THE ISSUES AROUND MARIJUANA, ET CETERA, SO IT'S AN ONGOING BATTLE, BUT I WOULD SAY THAT WHERE WE'RE GOING TO SOLVE IT IS AT THE COMMUNITY. ULTIMATELY, WE NEED ALL OF THE SCIENCE, FEDERAL SUPPORT, WE NEED STATEHOUSING SUPPORT, BUT ALL OF THE CRISES THAT HAVE EVER BEEN SOLVED HAVE BEEN SOLVED AT COMMUNITY AND WE NEED TO ALWAYS FIGURE OUT WHAT CAN WE GIVE THOSE PEOPLE OUT IN THE COMMUNITY TO TRULY SOLVE THESE PROBLEMS. AND I WILL CON CLYDE CLEUD BY CONCLUDE WE ARE JUST SO PROUD OF THE DATA ON OUR DRUG COMMUNITIES PROGRAM, THE PRESIDENT ANNOUNCED LAST WEEK THE GRANTS -- EVER INCREASING GRANTS FOR THAT PROGRAM. WE HAVE INDEPENDENT DATA FROM ICF THAT SAYS THAT WHEN WE GET ONE OF THESE COALITIONS, TRAIN THEM, THAT THEIR 30-DAY US A EUS ACROSS ALCOHOL, TOBACCO, MARIJUANA AND PRESCRIPTION DRUGS, THIS IS BASED ON EACH OF THE DRUG COALITIONS AND WHAT OTHER RATES ACROSS THOSE CATEGORIES ON 30-DAY USE. AND THEN HOW WE WOULD EVALUATE THEM ANNUALLY IS HOW ARE THEY BRINGING THOSE RATES DOWN. AND WHEN YOU ROLL ALL OF THAT MORE THAN 10,000 COALITIONS THAT HAVE EER BEEN IN THIS PROGRAM, ON AVERAGE, THEY HAVE DRIVEN THOSE RATES DOWN MORE THAN 20% FOR ALCOHOL, MORE THAN 30% FOR TOBACCO, NEARLY 10% FOR MARIJUANA, AND ALMOST 20% FOR PRESCRIPTION DRUG ABUSE. SO WHEN YOU PUT SOMETHING OUT IN THE COMMUNITY, YOU TREAT IT PROPERLY, GIVE IT THE RIGHT SCIENCE, THAT'S THE KIND OF RESULT YOU CAN GET. SO I WILL CONCLUDE MY DIALOGUE BY SAYING THANKS AGAIN, I APPRECIATE THE EMPHASIS ON PREVENTION, AND WE NEED TO WORK THE WHOLE CONTINUUM BUT UNDERSTAND THAT STOPPING IT BEFORE IT STARTS IS THE MOST COST-EFFECTIVE WAY TO DO THAT. >> ARTHUR, THANKS FOR YOUR COMMENTS. ANY MORE QUESTIONS? >> THE ONE THING TO ME, THE OPIOID EPIDEMIC REMINDS ME A LOT ABOUT THE BEGINNINGS OF THE HIV WE HAVE THE SAME PROBLEMS, WE HAVE OVER 2 MILLION PEOPLE ALREADY STARTING TO TACKLE THIS, WE HAVE MORE DEATHS FROM THE OPIOIDS THAN WE HAVE EVER HAD FROM HIV. WE HAVE STIGMA, WE HAVE ALL THE THINGS WE SAW IN THE EARLY HIV EPIDEMIC AND CONTINUE TO SEE. I THINK THAT THIS TO TAKE TO DR. COLLINS A ND OTHERS, I THINK THIS EPIDEMIC IS GOING TO REQUIRE A RESPONSE SIMILAR TO WHAT WE HAD FOR HIV HIV. IT'S NOT GOING TO BE OVER ANY TIME SOON, AND IF AND WHEN IT'S OVER, WE'LL HAVE YOU OR COLLINS IN AN AIRCRAFT CARRIER WITH A "MISSION ACCOMPLISHED" SIGN BEHIND YOU, BUT IN THE MEANTIME, IT'S GOING TO TAKE A WHILE. THIS IS GOING TO BE A LIFETIME OF WORK JUST LIKE IT'S BEEN WITH HIV. WE HAVE NOT GOTTEN THE HIV EPIDEMIC OVER. AND I REALLY THINK I WOULD ENCOURAGE YOU, NIH AND OTHERS TO THINK OF AN INTERDISCIPLINARY APPROACH, I THINK THIS IS GOING TO -- OPIATES COULD BE AT THE CENTER, BUT I THINK IT'S THE TIME TO TAKE AN APPROACH TO ADDICTION SIMILAR TO WHAT WE HAD FOR HIV BECAUSE OTHERWISE WE'RE SQUEEZING THE BALLOON HERE AND IT POPS OVER HERE. SO LET'S HAVE A BROADER VIEW, LET'S HAVE AN INTERDISCIPLINARY APPROACH AND, YOU KNOW, WITH NIMH, WITH NIND, WITH EVERYBODY, AND THINK ABOUT AN O RA. KIND OF APPROACH TO REALLY ADDRESSING THIS EPIDEMIC AT THE NIH LEVEL. I THINK ONLY THEN WILL WE REALLY HAVE THE KIND REEF SPONS WE'VE IN WITH INCREDIBLE DISCOVER REE MULTIPLE ADVANCES, ET CETERA, ET CETERA. >> I APPRECIATE YOUR COMMENTS AND ABSOLUTELY, AND THAT'S IN PART THE REASON WHY AS OF NOW, THE PROJECTS ARE BEING DRIVEN BY BUILDING 1, AND THEY'RE ACTUALLY ON ALL OF THESE PROJECTS, THEY ARE ENCOURAGING AND FAVORING PROJECTS THAT ENGAGE MORE THAN ONE INSTITUTE. I THINK YOUR POINT IS ALSO VERY WELL TAI TOO AS YOU'RE ADDRESSING THE ISSUE OF HOW DO YOU DEAL WITH THE OPIOID CRISIS AND THE HIV CRISIS, YOU NEED THE PARTNERSHIPS BETWEEN AGENCIES AND THE PARTNERSHIPS WITH PRIVATE INDUSTRY. AND THE COMMUNITIES BY ALL MEANS. AND THE HHS AND BRETT THE GIROIR HAS BASICALLY TAKEN THE BEAD LEED AND VERY AGGRESSIVELY BROUGHT US TOGETHER IN A VERY COMPREHENSIVE WAY TO FIGURE OUT THE STRATEGIC PLAN THAT BRINGS IT TOGETHER IN A WAY I ACTUALLY THINK HAVING GONE THROUGH THE SUCCESS OF T HE HIV BECAUSE EVEN THOUGH YOU STILL ARE BATTLING WITH IT, YOU WERE ABLE TO CONTAIN THAT EPIDEMIC AND SIGNIFICANTLY TO CHANGE THE WAY -- THE STIGMA AROUND IT AND TO DEVELOP TREATMENTS VERY RAPIDLY. WE DON'T HAVE THE LEVEL OF INVESTMENTS BUT I STILL THINK WE CAN EMULATE ALL OF THOSE THAT WERE VERY SUCCESSFUL WITH THE HIV AND THAT REQUIRES YESINTEGRATION OF OUR EFFORTS HERE WITHIN THE NIH BUT ALSO WITH THE AGENCIES, AND ACTUALLY CERTAINLY SAMHSA HAS BEEN KEY COLLABORATOR, CDC, HRSA, THE FDA, ALL OF THE DIFFERENT AGENCIES CAN PLAY EXTREMELY IMPORTANT ROLES. BUT I THINK WE CAN LEARN INDEED HOW WE DID THE HIV. >> AS FAR AS OPIOIDS AND INFECTIOUS DISEASE, IT SOUNDS LIKE SELF-PROMOTION BUT BECAUSE OF ADMIRAL GIROIR, THE NATIONAL ACADEMY OF SCIENCES ENGINEERING MEDICINE PUT TOGETHER A WORKSHOP THAT I CHAIRED AND THE PROCEEDINGS OF THE WORKSHOP HAVE BEEN RECENTLY RELEASED SO I WOULD PASS IT TO EVERYBODY. SAMMY SPRINGER -- I WROTE AN EDITORIAL THAT BASICALLY HAS FIVE ACTION STEPS TO INTEGRATE INFECTIOUS DISEASE TO THE OPIOID EPIDEMIC, AND I WOULD ENCOURAGE EVERYBODY TO HAVE THOSE. >> VERY TIMELY POINT. THE OTHER THING RADONNA CHANDLER, ALSO HER OTHER HAT IS AS DIRECTOR OF THE HIV -- ONE OF THE THINGS THAT SHE'S PLANNING TO DO IS TO BRING A GROUP OF SCIENTISTS TO ACTUALLY IDENTIFY WHAT ARE GOING TO BE ONE OF THE PRIORITIES ON HOW THIS CAN ACTUALLY VERY MUCH DOVETAIL WITH THE OPIOID CRISIS. SO THIS IS VERY MUCH IN LINE WITH WHAT WE'RE ACTUALLY THINKING TO MOVE FORWARD. IN OUR HIV PORTFOLIO. ROBERT? >> NORA, JUST A VERY BRIEF COMMENT. BEING IN THE JUSTICE SYSTEM, WE'RE HEARING A LOT ABOUT THINGS RELATING TO THE JUSTICE SYSTEM. ONE OF THE THINGS THAT HAS ALWAYS AMAZED ME IS AS A JUDGE IS LACK OF MANDATORY TRAINING. WE HAVE AS JUDGES IN MEDICATION ASSISTED TREATMENT ADDICTION, PERIOD, TRAUMA RELATED ACTIVITIES, CO-MORBIDITY, ALL OF IT. AND I THINK ONE OF THE SUGGESTIONS I WOULD MAKE IS MAYBE TO REACH OUT TO THE CONFERENCE OF CHIEF JUSTICES, THAT THEY NEED TO HAVE MANDATORY CONTINUING LEGAL EDUCATION AS IT RELATION TO IN JUDICIAL TRAINING MEDICATION-ASSISTED TREATMENT. BECAUSE I THINK ONE OF THE DISCONNECTS IS WHEN THE PEOPLE DO APPEAR BEFORE US IN THE COURTS ON A DAILY BASIS, THE LACK OF KNOWLEDGE I THINK A LOT OF JUDGES HAVE IN THAT AREA. SO THAT WOULD JUST BE A SUGGESTION. >> THAT'S AN EXTREMELY IMPORTANT POINT, AND I DO KNOW CERTAINLY WILL WILSON HAS DONE IT, CARLOS HAS DONE IT TOO AND RADONNA AND TISHA HAVE BASICALLY SPOKEN IN MEETINGS FOR FEDERAL JUDGES AND PROSECUTORS, BUT THAT IS ONE COMOANT, WHAT YOU ARE SAYING IS COULD THERE BE LIKE A SYSTEMATIC NEED OF TRAINING. AND I DON'T KNOW SUFFICIENTLY TO ACTUALLY BE ABLE TO RECOMMEND WHAT IS THE BEST WAY TO MOVE THAT FORWARD, BUT WE WOULD WELCOME YOUR SUGGESTIONS IN TERMS OF WHAT IS IT THAT NIDA COULD DO TO HELP MAKE THIS HAPPEN. WE'RE GOING TO START BY DOING THIS SERVICE AND GETTING A PERSPECTIVE OF WHAT ARE THE ROAD BLOCKS FOR IMPLEMENTING MEDICATIONS AND I PREDICT THAT ONE OF THEM IS LACK OF TRAINING, AMONG OTHER THINGS, BUT FROM THERE, HOW DO UP CHANGE -- I MEAN, HOW DO YOU CREATE A MANDATE FOR EDUCATION. WE HAVE NOT BEEN SO VERY SUCCESSFUL WITH A MANDATE FOR EDUCATION OF MEDICAL STUDENTS OR RESIDENTS IN PSYCHIATRY. HOW DO YOU GET TOUCH INTO JUDGES. BUT I THINK WE SHOULD BRAINSTORM AND SEE WHAT ARE THE ROLES THAT WE HAVE TO BE ABLE TO GET THEM INCENTIVIZED TO DO THAT, BECAUSE I SUSPECT THEY ARE NOT GOING TO BE DOING IT BECAUSE NIH SAYS. I SUSPECT IT HAS TO COME THROUGH THEM BECAUSE THEY SEE THE VALUE. LINDA. >> JUST A COMMENT ABOUT WHEN I SEE THIS, ESPECIALLY WITH THE BASIC SCIENCE RESEARCH, THEY OFTEN ONLY LOOK AT A SINGLE DRUG OR MEDICATION AND THE TREATMENT APPROACHES OFTEN TARGETING ONLY ONE RECEPTOR OR ONE DRUG, AND YET IN THE REAL WORLD OR OF OUR DRUG USING POPULATION ARE USING, YOU KNOW -- INCLUDING THE LEGAL DRUGS TOO, TOBACCO, ALCOHOL, JUST LIKE WHAT WAS SAYING, IT'S CERTAINLY A WHACK MOLE THING, YOU TRY TO HAVE THEM DECREASE THE USE OF ONE DRUG THEN THEY END UP USING MORE, SMOKE MORE OR DRINK MORE, AND SO I THINK MAYBE IT WOULD BE INTERESTING TO HAVE SOME MORE FOCUS ON TREATING ADDICTION AS A WHOLE INCLUDING THE POLY-DRUG USING BEHAVIOR AND PATTERN. I DON'T REALLY -- I DON'T HAVE THE ANSWER FOR IT, BUT I'M THINKING LIKE -- BECAUSE EVERY TIME I SEE AN ANIMAL MODEL STUDY, IT'S VERY, VERY SPECIFIC FOR ONE DRUG ONLY, AND IF IT WORKS FOR THAT, IT DOESN'T ALWAYS WORK IN THE HUMAN CONDITION. PLAWSH SOSO I DON'T KNOW IF THERE COULD BE A SPECIAL MECHANISM THAT FOCUSES ON HOW TO EVALUATE TREATING POLYSUBSTANCE WITH MORE THAN ONE COMBINATION. JUST LIKE WE TREAT INFECTIONS WITH MORE THAN ONE ANTIBIOTICS AND YOU GET BETTER EFFECTS. SO I'M JUST WONDERING IF THEY'RE KIND OF THINK -- THAT KIND OF THINKING CAN BE APPROACHED, ESPECIALLY IN BASIC SCIENCE RESEARCH. BECAUSE I NEVER SEE ANIMAL MO MODELS WHERE THEY LOOK AT MORE THAN ONE DRUG AT A TIME. >> LINDA, THIS IS SOMETHING THAT WE'VE BEEN VERY SENSITIVE TO, AND IN FACT, ONE OF THE FIRST PROJECTS WITH THE CRAN WHICH IS ALCOHOL AND NCI AND NIDA, PROGRAM TOGETHER WAS EXACTLY TO DO THAT, TO CREATE ANIMAL MODELS THAT ALLOWED US TO INVESTIGATE THE CO-MORBIDITY BETWEEN NICOTINE AND ALCOHOL AND ALCOHOL AND OTHER DRUGS. I'VE BEEN PUSHING THAT AND I REMEMBER AND WHEN I HAD JUST GONE TO NIDA FROM THE BEGINNING AND GEORGE COUP WAS INVESTIGATOR AND SAYS NORA, WE PUT THESE GRANTS AND IN THE STUDY SECTIONS ACTUALLY RATES THEM VERY POORLY, SO I WENT TO SUSAN AND I SAID SUSAN, CAN WE LOOK INTO WHETHER THIS IS THE CASE OR NOT, WHETHER GRANTS THAT ARE AIMING TO STUDY MORE THAN ONE SUBSTANCE ARE DOING WORSE, AND SHE LOOKED INTO IT AND WE COULDN'T REALLY IDENTIFY THAT THERE WAS A -- ITSELF SO THAT WE COULD INTERVENE AT THE LEVEL OF THE STUDY SECTION. WE ENCOURAGE RESEARCHERS TO COME UP WITH MORE COMPLEX MODELS, SO ANIMAL MODELS THAT RELATE BETTER TO THE REALITIES OF SUBSTANCE USE DISORDERS. IN THE CLINIC, WE ARE ACTUALLY ALSO ENCOURAGING RESEARCHERS TO JUST EVEN AS A NON-BRAINER, TO UNDERSTAND THE INFLUENCE THAT THE INTERVENTION HAS ON THE CONSUMPTION OF OTHER DRUGS BECAUSE THIS IS SOMETHING THAT YOU HAVE THE DATA AND IT'S NOT NECESSARILY BEING LOOKED AT, SO FOR EXAMPLE, YOU DO AN INTERVENTION FOR AN OPIOID USE DISORDER, WHAT DOES DO TO SMOKING, TO DRINKING? THAT IS NOT -- I MEAN, UNFORTUNATELY, SYSTEMATICALLY EVALUATED, SO WE'RE TRYING TO CHANGE THAT MENTALITY. BUT ALSO I THINK AS WE LOOK FORWARD IN THE WAY THAT WE CONCEIVE ALL TREATMENTS FOR ADDICTION IN GENERAL IS THE RECOGNITION THAT -- AND AGAIN, IT'S NOT JUST ABOUT ABSTINENCE, IT'S ABOUT DISSECTING THE NEUROCIRCUITRY AND THE SYMPTOMS THAT LEAD A PERSON TO SEEK THE DRUGS AND THEY'RE GOING TO BE COMMON AND THEY'RE GOING TO BE SPECIFIC. THEY'RE GOING TO BE SPECIFIC BECAUSE FOR EXAMPLE, WITH OIP YOID USE, OF COURSE, YOU DEVELOP THE PHYSICAL DEPENDENCE AND THE TOLERANCE THAT CONTRIBUTES TO WITH WITHDRAWAL, BUT THEY'RE GOING TO BE COMMON, LIKE THE WHOLE DISRUPTION OF THE MOOD CIRCUITRY THAT LEADS TO DYSPHORIA AND TO ANXIETY. THE DISRUPTION OF COGNITIVE OPERATIONS THAT LEADS YOU TO COMPULSIVE BEHAVIORS. SO TARGETING INTERVENTIONS THAT CAN STRENGTHEN THAT NEUROCIRCUITRY COULD HELP YOU BUFFER ADDITION IN GENERAL. WE ARE ACTUALLY ENCOURAGING RESEARCHERS AND THIS COULD BE THROUGH A MEDICATION THAT IT IMPROVES COGNITIVE PERFORMANCE, THINGS THAT ACTUALLY STRENGTHENS THIS PROCESS OR ARE SIMULATION TECHNOLOGIES LIKE DIRECT ELECTRICAL CURRENT STIMULATION, MAGNETIC STIMULATION, CREATE AN ARMAMENT OF INTERVENTIONS THAT CAN STRENGTHEN THE NEUROCIRCUITRY AND THEREFORE THE LIKELIHOOD OF THE PERSON EXCEEDING. BY ITSELF, WE ARE ALSO VERY INTERESTED ON THE POTENTIAL USE OF SOME OF THESE MEDICATIONS ACTUALLY FOR TREATMENTS OTHER THAN MARIJUANA, SO IN THE SCIENTIFIC PERSPECTIVE, IT MAKES NO SENSE TO VERY NICELY DELINEATE AND SEPARATE THEM BECAUSE THESE NEUROCIRCUITRIES INTERACT WITH ONE ANOTHER AND DRUGS -- AS WE WERE DISCUSSING BEFORE, IT'S NOT A REALITY, PEOPLE DON'T JUST WANT ONE DRUG, THAT'S NOT THE WAY IT COMES. SO THE POINT IS VERY WELL TAKEN LIKE THE POINT ABOUT ACTUALLY THIS IS THE TIME TO RECOGNIZE THAT WE NEED TO TACKLE ADDICTION AND THAT'S WHY I SAY YES, GUYS, I'M SPEAKING ABOUT THE HEAL, BUT WE HAVE CANNA BUSINESS, WE CANNABIS, ELECT RONIC CIGARETTES, COCAINE, METHAMPHETAMINE, SIN THEY TICS. THIS IS THE SYNTHETICS. YOU SAY OKAY, YOU HAVE THE MONEY FOR HIV, THEN THE INFECTIOUS DISEASE INSTITUTE WILL -- THEY CONTROL IT, THEY HAVE CURE, NO MORE NEED. THEN COME -- IT'S ACTUALLY THAT RECOGNITION THAT THIS IS UNFORTUNATELY A VULNERABILITY IN TERMS OF NEUROCIRCUITRY, OUR SOCIETY, ACCESS TO THESE DRUGS THAT KISS RUPT BEHAVIOR OR DISRUPT BHIEF D ISRUPT BEHAVIOR. >> FIRST THANK YOU FOR INVITING ME TO JOIN THE COUNCIL. LET ME ALSO THANK YOU AND THE ENTIRE NIDA COMMUNITY FOR DRIVING YOUR NOBLE VISION AND MISSION. TO REALLY SUPPORT A POPULATION THAT IS AND IS STILL UNDERSERVED. TWO POINTS. THE FIRST ONE IS DURATION OF TREATMENT. YOU MENTIONED THAT IN YOUR PRESENTATION, AND TODAY IN THIS COUNTRY, PATIENTS THE WHO HAVE ACCESS TO TREATMENT ARE TREATED FOR ON AVERAGE TWO OR THREE MONTHS. IT IS ABSOLUTELY MIND BLOWING TO THINK THAT PATIENT ARE BEING TREATED FOR OPIOID USE DISORDER ON AVERAGE FOR TWO OR THREE MONTHS. SO THE REASON WHY I'M SAYING THAT IS THAT THERE IS A NEED FOR LONG TERM STUDIES, THESE ARE PATIENT OUTCOMES, RESEARCH STUDIES, IN REAL WORLD, WHERE WE CAN REALLY FOLLOW THOSE WHO HAVE ACCESS TO TREATMENT VERSUS THOSE WHO DO NOT HAVE ACCESS TO TREATMENT, AND CLEARLY DEMONSTRATE THAT M.A.T. WILL HAVE AN IMPACT ON THE QUALITY OF LIFE, BUT WE NEED TO GENERATE THE DATA AND WE DON'T HAVE ENOUGH DATA RIGHT NOW. SO WE ARE TALKING ABOUT NOT FOLLOWING PATIENTS FOR SIX MONTHS, WE ARE TALKING ABOUT FOLLOWING PATIENTS FOR ONE YEAR, TWO YEARS, THREE YEARS, FOUR YEARS, FIVE YEARS, IDEALLY, THAT IS ABSOLUTELY REQUIRED ALSO IN ORDER TO CONVINCE PAYORS THAT THIS IS NOT A TWO OR THREE-MONTH DEAL. PATIENTS WILL HAVE TO STAY IN TREATMENT FOR EXTENSIVE PERIODS OF TIME. AND WE OWE TO THE PAYORS TO GENERATE THE DATA TO CONVINCE THEM THAT THIS IS WHAT'S GOING TO BE REQUIRED. THE SECOND POINT, YOU MENTIONED MEDICATION -- END POINTS OTHER THAN OH ABSTINENCE. YOU MENTIONED INSOMNIA, CRAVING, DYSPHORIA, DYSFUNCTION, AND I THINK THIS IS A VERY, VERY IMPORTANT POINT. I SAW SOME ENCOURAGING STATEMENTS FROM THE FDA COMMISSIONER, DR. SCOTT GOTTLIEB, MENTIONING MORE SPECIFICALLY CRAVING, BUT THE KEY QUESTION IS WHAT CAN WE DO TOGETHER IN ORDER TO INCENTIVIZE THE FOOD AND DRUG ADMINISTRATION TO REALLY NOT LOOK AT THESE END POINTS AS EXPLORATORY END POINTS, BUT REALLY LOOK AT THEM AS PRIMARY CLINICAL END POINTS SO THAT WE WILL MOVE AWAY FROM AN ABSTINENCE-ONLY FOCUS. I THINK IT IS ABSOLUTELY CRITICAL AND I AM CONVINCED THAT WE CAN WORK TOGETHER IN ORDER TO VALIDATE SOME OF THESE NEW END POINTS, BUT THAT IS GOING TO BE CRITICAL FOR MEDICATIONS DEVELOPMENT. >> CHRISTIAN, THANKS FOR THOSE POINTS, I ABSOLUTELY AGREE, THAT WAS ONE OF THE, I THINK, POSITIVE OUTCOMES THAT CAME OUT OF PUBLIC-PRIVATE PARTNERSHIP MEETINGS THAT WE HAD, IT BROUGHT TO LIGHT THE IMPORTANCE OF THE FDA WORKING CLOSELY WITH ACADEMIA AND PRIVATE INDUSTRY AND TO HELP DEVELOP ALTERNATIVE OUTCOMES THAT WILL BE ACCEPTED BY THEM, SO YES, WE HAVE TO DEMONSTRATE THAT THEY HAVE MEANINGFUL SIGNIFICANCE, SO THAT'S WHERE RESEARCH COMES INTO PLAY AND WE ARE VERY AWARE OF THE IMPORTANCE ALSO OF DOING LONG TERM STUDIES OF OUTCOMES AND COMPLETELY RECOGNIZE THAT THREE MONTHS OF TREATMENT IS ACTUALLY MALPRACTICE, IF YOU THINK ABOUT IT IN TERMS OF THE VERY HIGH RISK OF MORTALITY ASSOCIATED WITH AN OPIOID USE DISORDER, YOUR CHANCES OF DYING ARE AT LEAST THREE FOLD HIGHER THAN IF YOU'RE NOT TREATED. WE KNOW THAT. WHAT WE DO NOT KNOW IS SO YOU NEED TO BE TWO YEARS, THREE YEARS, FOUR YEARS, FIVE YEARS, AND WHAT ARE THE CHARACTERISTICS, AND DO YOU NEED TO BE ALWAYS ON THE SAME MEDICATIONS OR IS THERE AN OPPORTUNITY TO ACTUALLY MODIFY. NONE OF THAT WORK HAS BEEN -- IT HAS BEEN DONE FOR OTHER AIRS MEFD SIN BUT IT'S ABSOLUTELY CLEAR THAT WE DON'T NEED TO DO ANY MORE STUDIES, WE KNOW LESS THAN SIX MONTHS OF TREATMENT ACTUALLY IS ASSOCIATED WITH HIGHER MORTALITY. SUSAN IS TELLING ME WE SHOULD END. SO ACTUALLY IT IS END FOR THE TIME BEING, AND WE ARE GOING TO WANT YOU TO COME BACK AT 1:30, AND WE ARE GOING TO -- ERIC DISHMAN WHO DIRECTS THE ALL-OF-US PROJECTS IS GOING TO BE COMING UP AND GIVING YOU AN A UPDATE, AND THIS IS EXTREMELY INTERESTING STUDY. SO 1:30 HERE. YOU ARE IN FOR A TREAT AND IT'S REALLY A PLEASURE FOR US TO HAVE DR. ERIC DISHMAN COME AND SPEAK TO YOU. HE'S THE DIRECTOR OF THE ALL-OF-US RESEARCH PROGRAM AT THE NIH AND YOU HAVE ACTUALLY HEARD ALREADY ABOUT THIS PROGRAM. I WAS PROMISING -- SO I'M DELIVERING THE PROMISE. DR. DISHMAN JOINED THE NATIONAL INSTITUTE OF NIH IN 2016 AS DIRECTOR FOR ALL-OF-US RESEARCH. IN THIS ROLE, HE LEADS THE AGENCY TO BUILD A NATIONAL RESEARCH COHORT OF 1 MILLION OR MORE U.S. PARTICIPANTS TO ADVANCE PLEA SITION MEDICINE. PREVIOUSLY HE WAS INTELFELLOW GENERAL MANAGER OF THE HEALTH AND LIFE SCIENCES GROUP IN THE DATA CENTER AND CONNECTED SYSTEMS GROUP, WHERE HE WAS RESPONSIBLE FOR DRIVING INTEL'S BUSINESS STRATEGY, RESEARCH AND DEVELOPMENT AND PRODUCT AND POLICY INITIATIVES FOR HEALTH AND LIFE SCIENCES SOLUTIONS. HE'S RECOGNIZED AS A GLOBAL LEADER IN HEALTHCARE INNOVATION WITH SPECIFIC EXPERTISE IN HOME AND COMMUNITY-BASED TECHNOLOGIES AND SERVICES FOR CHRONIC DISEASE MANAGEMENT AND INDEPENDENT LIVING. HE'S ALSO KNOWN FOR PIE OWE NEARING INNOVATION TECHNIQUES THAT INCORPORATE THE ANTHROPOLOGY, AND OTHER SOCIAL SCIENCES METHODS INTO THE DESIGN AND DEVELOPMENT OF NEW TECHNOLOGIES. ERIC, THANKS VERY MUCH FOR TAKE THE TIME AND COMING TO SPEAK WITH COUNCIL. >> THANK YOU SO MUCH FOR HAVING ME. CAN YOU HEAR ME OKAY? I HAD TO GO MOBILE. I THINK IT'S THE WAY I SORT OF WORK OUT MINER VUS MY NERVOUSNESS. IT IS A GREAT HONOR TO BE HERE. HONESTLY, BASICALLY I'M A SOCIAL SCIENTIST WHO WANTED TO STUDY THE OBSCURITIES OF CONVERSATION, I'M TRAINED IN AN AREA CALLED CONVERSATION ANALYSIS. IN THOSE DAYS WE DIDN'T HAVE COMPUTERS THAT CAN TRANSCRIBE HUMAN SPEECH AS IT CAN NOW, SO THE GRADUATE NUMBER OF HOURS I SPENT TRYING TO GET THE HU HU, HA, HA, IT ENDED UP BEING A POTENTIALLY INTERESTING VITAL SIGN THAT YOU COULD ACTUALLY LOOK AT, SO THAT WAS EARLY WORK I DID, THAT WAS A LONG TIME AGO, SO I'VE BEEN IN SILICON VALLEY FOR 25 YEARS, HERE FOR TWO, SO THAT WAS A A REALLY LONG TIME AGO. BUT FUNDAMENTALLY I'M A PATIENT AND PATIENT ADVOCATE, I'LL SHARE A LITTLE ABOUT YOU WITH MY OWN 23-YEAR CANCER JOURNEY, IT WAS GREAT FUN. I DO A LOT OF PATIENT ADVOCACY FOR PATIENTS MOSTLY DEALING WITH KIDNEYS, KIDNEY CANCER, TO UNDERSTAND THE HEALTH SITUATION DEEPLY AND BROADLY. SO MANY OF WHAT WE HAVE HAD SORT OF SOUND BITES ABOUT PATIENTS' LIVES AND IT'S LIKE I WANT THE FULL MOVIE, NOT THE SOUNDBITE, BECAUSE THE MULTIPLE FACTORS IN PEOPLE'S LIVES HAVE SO MUCH TO DO WITH THE PRESENCE OR ABSENCE OF HEALTH. I WANT TO THANK DR. JOANIE RUDDER FROM MY TEAM, LIAISON TO NIDA, ALSO EMILY EINSTEIN, THE LIAISON FROM NIDA TO OUR GROUP. WE ARE A SMALL STARTUP GROUP BUT WITH 27 INSTITUTES AND CENTERS, WE TRY TO MAKE SURE WE HAVE AT LEAST SOME CONNECTION POINT, SO THIS IS OUR WHOLE LIAISON TEAM ACROSS ALL THE 27 INSTITUTES AND CENTERS SH SO REALLY APPRECIATE THEM SORT OF MAKING THOSE CONNECTIONS AND HELPING TO CONNECT OUR WORK BROADLY ACROSS THESE TWO AREAS. ALSO SITTING WITH THEM IS MY COLLEAGUE WHO HELPS ME PREPARE FOR ALL OF THESE, I SHOULD GIVE HER ALL CREDIT FOR THE STUFF THAT GOES WELL, AND NEXT TO HER IS HER FIFTH HOUR ON THE JOB, OUR CHIEF MEDICAL AND SCIENTIFIC OFFICER DR. KELLEY JIBO, JOHNS HOPKINS, ESPECIALLY IN THE AREA OF AIDS AND REALLY EXCITED TO HAVE HER JOIN OUR SENIOR LEADERSHIP TEAM TO HELP PLAN THE SCIENTIFIC ROAD MAP OVER TIME. THIS IS HER FIRST COUNCIL MEETING. SO THIS IS ME AT AGE 19 IN THE SUMMER OF 1989 IN VERY HOT, HUMID CHAPEL HILL, MUCH LIKE IT IS TODAY. WE NEED TO STOP THIS WEATHER TODAY IF WE CAN GET RID OF IT. I STARTED CHEMO -- MY WIFE WAS LIKE I'VE GOT TO DISTRACT HIM. THEY SAID YOU HAVE NINE MONTHS TO LIVE, YOU HAVE A RARE FORM OF KIDNEY CANCER, I WENT INTO A DEEP DEPRESSION, AND ASHLEY WAS DOING ANYTHING SHE COULD TO SAVE MY LIFE AND SHE'S LIKE, I'LL GET HIM A PUPPY, AND IT HELPED. IRONICALLY, THAT DOG LIVED FOR 14 YEARS, ABBY, AND SHE DIED OF KIDNEY CANCER, STRANGELY ENOUGH. BUT THE WHOLE EXPERIENCE, SOME OF YOU MAY HAVE HEARD ABOUT MY CANCER STORY. YES, IT LASTED 23 YEARS, I HAD 57 ROUNDS OF CHEMOTHERAPY MIXED IN WITH SOME RADIATION, IMMUNOTHERAPY, AFTER THE FIRST 10 YEARS I SAID STOP TELLING ME I'M GOING TO DIE IN NINE MONTHS, YOU'RE NOT DOING WELL ON YOUR BATTING AVERAGE. IF PEOPLE CAN'T SHAKE THEMSELVES OUT OF THAT NUMBER, THEY ALMOST DIE ON TIME AS IF IT'S A PRESCRIPTION SO I REALLY GET PEOPLE TO FIGHT IT. BUT THE LESSON I LEARNED EARLY ON, THE WOMAN WHO TAUGHT ME TO YOU HOWE DO PATIENT ADVOCACY, WE WENT OVER TO THE DUKE MEDICAL LIBRARY WE WERE TRYING TO PULL OUT THE STUDYS THAT HAD BEEN DONE ON THIS RARE KIDNEY CANCER, FINALLY AFTER TWO HOURS -- SHE WAS AN ACTUARY SO HER STATISTICS WAS MUCH BETTER THAN MINE. SHE POPS UP AND SAYS, ERIC, THEY DON'T UNDERSTAND ANYTHING ABOUT YOU. I SAID WHY DO YOU SAY THAT? SHE SAID THEY'VE HAD THREE STUDIES IN EXISTENCE ABOUT THIS SUPPOSED DISEASE YOU'VE HAD, ALL OF THEM WERE OVER 65 AND THE VAST MAJORITY OF THE PEOPLE WERE 75 OR 80. SO WE DON'T KNOW ABOUT YOUNG PEOPLE AGED 19 GETTING THIS DISEASE AND YOU'VE GOT TO STOP LETTING THAT YOU'RE GOING TO DIE IN NINE MONTHS. REALLY, I DIDN'T KNOW THAT, BUT LOOKING BACK ON IT, IT WAS WELL-INTENTIONED IMPRECISION MEDICINE. WE WERE USING THE BEST TOOLS, BEST SCIENCE, BEST DATA THAT WE HAD. I WAS TREATED IN SOME OF THE BEST PLACES AROUND THE COUNTRY FOR ONCOLOGY BUT AT THE END OF THE DAY, WE DIDN'T HAVE THE SCIENCE, WE DIDN'T HAVE THE DATA TO BE ABLE TO TREAT ME AS AN INDIVIDUAL. AT THE END OF THAT LONG STORY, HERE I WAS VICE PRESIDENT AT INTEL, RUNNING THIS BIG HEALTH AND LIFE SCIENCE BUSINESS ACROSS ALL THESE COUNTRY, FINALLY THE CANCER WIPED OUT BOTH KIDNEYS, I WAS IN KIDNEY FAILURE FOR THREE YEARS BUT NOT ON DIALYSIS, I WAS LIKE I'M FINE, I CAN MAKE IT, BUT IT WAS FINALLY CATCHING UP WITH ME, AND IT WAS MY LAST BUSINESS TRIP DOWN TO -- WE WENT UP TO BOSTON, ONE OF THE HOT BEDS OF PARTICULARLY GENOMICS, TRYING TO DO PROCESSING OF LARGE EHR DATA, AS WELL AS SAN DIEGO. IN SAN DIEGO, THERE WAS A STARTUP COMPANY, ONE OF THE FIRST VISUALIZATION TOOLS FOR RESEARCHERS, ON TRYING TO UNDERSTAND LOOKING AT WHOLE GENOME SEQUENCING DATA, EHR DATA, TRYING TO CAMPAIGN THEM, AND THE CTO OF THAT COMPANY SAID, ERIC, YOU DID SPEAK AT A KIDNEY CONFERENCE AS A PATIENT LIKE 10 YEARS AGO? I SAID YES, HE SAID ARE YOU DOING OKAY? I SAID YOU'RE PROBABLY GOING TO NEVER SEE ME AGAIN, ONCE I WENT ON DIALYSIS, IT WAS NOT GOING TO BE A PRETTY PICTURE. HE SAID WELL, WE'LL HELP YOU THE GET ALL YOUR EHR DATA TOGETHER AND WE'D BE HAPPY TO DO A WHOLE GENOME SEQUENCE FOR YOU. THEY WANTED INTEL TO INVEST IN THEIR COMPANY SO THEY WERE DOING EVERYTHING THEY COULD TO IMPRESS ME. I ASKED FOR MY DATA, SO I HAD THREE 1 TERABYTE HARD DRIVES SHOW UP, I WAS LIKE, I AM AN INTEL GUY AND I DON'T KNOW WHAT THE HELL TO DO WITH THIS. THEN THEN THEY CAME BACK AND AFTER FOUR MONTHS, I JUST HAD THE A.V. FISTULA IN FOR KIE AL CYST, DIALYSIS, THEY SAID WAIT, WAIT, WE'RE TRYING TO UNDERSTAND WHAT THIS MIGHT MEAN AND THE LONG STORY SHORT IS WE THINK MORE THAN 90% OF WHAT WE PUT YOU ON WAS DESTINED NEVER TO WORK. I WAS LIKE, GREAT, BECAUSE INTERLEUKIN 2 IS SO MUCH FUN. BUT THEY SAID WE THINK THE MECHANISM THAT MIGHT MITING CAUTIOUS THE CANCER IN YOUR KIDNEY IS SOMEWHAT RELATED TO THOSE FOR PANCREATIC CANCER, COULD YOU WITHHOLD TWO MORE MONTHS ON DIALYSIS AND UNDERGO CHEMO FOR PANCREATIC CANCER? I CAME OUT IT OF IT UTTERLY CANCER-FREE FOR THE FIRST TIME IN 23 YEARS. THE INTEL EMPLOYEE WHO DID NOT KNOW MEADOW NATEED A KIDNEY TO ME, AND I JUST TURNED 50, SO THIS IS MY MONTH, MY ANNIVERSARY MONTH, SEVEN YEARS AGO TODAY ROUGHLY I BECAME CANCER-FREE, AND SIX YEAR AGO TODAY ROUGHLY I GOT MY KID CAN KNEE KIDNEY TRANSPLANT. ON THE TABLE, MY WIFE RECORDED TO, I'VE LISTENED TO IT, IT'S IMBEARSING, YOU'RE WAKING UP FROM ANESTHESIA FROM A KIDNEY TRANSPLANT, I'M LIKE, WE'VE GOT TO FIGURE OUT HOW TO THIS TO EVERYBODY ELSE. HERE I AM A WHITE GUY, WEALTHY, I BARELY GOT ACCESS TO THIS PRECISION MEDICINE, WHAT ABOUT EVERYBODY ELSE? SO WHEN THIS OPPORTUNITY CAME ALONG TO LEAD THIS PROGRAM, I KNEW I WAS ON THE PLANET TO DO THIS AS I GO FORWARD. BUT WHAT PEOPLE DON'T KNOW ABOUT THIS, STORT EE THAT I TELL IS, THEY DON'T KNOW ABOUT MY STORY OF CHRONIC PAIN, AND THE CHRONIC PAIN THAT I HELPED MANY PEOPLE WITH KIDNEY PROBLEMS AND CANCER DEAL WITH. FOR THE EIGHT YEARS INITIALLY OF MY DISEASE, I DID NOT HAVE ANY EVIDENCE I REALLY THIS OTHER THAN THE DIAGNOSTICS THEY WERE DOING. THEY COULD SEE THE SCANS, I COULD SEE THE TUMOR WAS GETTING SMALLER, WHEN IT JUP JUMPED TO THE RIGHT, BUT EVENTUALLY IT STARTED PRESSING ON THE RADIAL NERVE AND I HAD PAIN. I WAS RELIEVED, THERE WAS BODILY JUSTIFICATION FOR WHAT YOU'VE DONE TO ME, BUT FOR THE WEEKS THAT CAME AFTER, IT WAS LIKE, MAN, THIS IS A FUNDAMENTAL CHOICE TO MAKE, AND FOR A VERY LONG TIME, I WOULD HAVE TO MAKE DAILY DECISIONS ON WHETHER I WANTED TO BE IN PAIN, DOPED UP OR BALANCING THOSE THINGS AS WE WALKED THROUGH THERE. THE CHRONIC PAIN JOURNEY, I COULD TELL YOU AN HOUR'S WORTH OF STORIES JUST ABOUT THAT AND MY OWN CHRONIC PAIN JOURNEY AND KINDS OF THINGS I DO. I'VE LEARNED SOME MEDITATION TECHNIQUES WHICH HELPED ME WITH ALLEVIATION. I CAN TAKE PAIN FROM MY BODY, PUT IT DOWN IN MY LEFT ANKLE THAT WAS MORE MANAGE AFNLT REALLY WEIRD THING TO SAY, BUT I LEARNED HOW TO DO THIS. THAT CHRONIC PAIN STRUCK WITH ME AND FIRST TIME THAT NORA AND I SPOKE, STARTED TO UNDERSTAND HOW MUCH WE REALLY DON'T UNDERSTAND THE TRANSITION FROM ACUTE PAIN TO CHRONIC PAIN, AND THEN THE VARIETY OF FACTORS THAT MAY COME TO BEAR TO HELP AN INDIVIDUAL EITHER PREVENT THAT TRANSITION OR TO DEVELOP A PROGRAM THAT'S GOING TO WORK FOR THAT UNIQUE INDIVIDUAL, IT SEEMED LIKE A RIPE OPPORTUNITY FOR THE ALL-OF-US RESEARCH PROGRAM. AND ONE OF THE REASONS I WANT TO SHARE THIS PROGRAM WITH YOU TODAY, YOU WHO KNOW FAR MORE ABOUT THIS THAN I DO, HELPING TO UNDERSTAND WHAT WE'RE DOING ENOUGH TO THEN START IMAGINING HOW COULD YOU USE THIS FOR THINGS TO REALLY ADVANCE, THE BROADER ISSUES AROUND SUBSTANCE ABUSE AND A LOT OF THE CHRONIC PAIN THAT UNDERLIES THOSE. SO THIS IS THE ESSENCE OF OUR PROGRAM. HOW DO WE ACCELERATE HEALTH RESEARCH AND MEDICAL BREAKTHROUGHS TO ENABLE INDIVIDUALIZED PREVENTION, TREATMENT AND CARE FOR ALL OF US, AND TO DO THIS, I COME FROM A WORLD WHERE WE HAVE STRATEGIC OBJECTIVE, ALL OF OUR MONTHLY OBJECTIVES LINE UP TO THOSE, WE'RE CREATING THAT CULTURE FOR OURSELVES. FIRST AND FOREMOST, WE NEED TO NEWER TEU RELATIONSHIPS WITH A MILLION OR MORE PEOPLE AS PARTICIPANTS IN OUR PROGRAM FOR ALL WALKS OF LIFE FOR DECADES. I SAY THIS IS KIND OF LIKE FRAMINGHAM BUT MUCH LARGER, MUCH MORE DIVERSE AND MUCH MORE FOCUSED ON A WIDE RANGE OF CONDITIONS OTHER THAN JUST HEART DISEASE AND TO DO THAT, WE HAVE TO BUILD FRAMINGHAM-LIKE LOCAL RELATIONSHIPS BUT ON A NATIONAL SCALE. PEOPLE ARE NOT GOING TO STAY IN THIS FOR THE DECADES AND HAVE THE TRUST AND THE STAYING POWER TO BE WITH US FOR THE DECADES THAT WE HOPE THIS BECOMES. IF WE DO THAT WELL, WE'LL DELIVER ONE OF THE RICHEST BIOLOGICAL MEDICAL RESOURCES EVER, AS SAFE AND FREE AND EAZ EE TO USE, WE'RE WORKING ON CERTAIN AMOUNTS OF THAT TO SAY, HEY, EVERYBODY CAN USE THIS. IF WE DO THAT, IF WE BUILD IT, WILL THEY COME, RIGHT? I DON'T WANT A FIELD OF DREAMS WHERE WE BUILD A LARGE COHORT PROGRAM WITH ALL THIS DATA AND WE HAVE TO ADMIT, SOME OF OUR LARGE INVESTMENTS IN COHORTS HAVE NOT BEEN ADEQUATELY USED TO JUSTIFY THEIR EXPENSE. HOW DO WE CATALYZE A RESEARCH ECOSYSTEM THAT'S GOING TO BE HUNGRY AND OTHER FUNDERS WHO ARE GOING TO DO THIS? WE DO NOT HAVE THE FUNDING TO FUND THE SCIENCE. WE HAVE THE FUNDING TO BUILD THIS NATIONAL PUBLIC RESOURCE AND THE OTHER 27 INSTITUTES AND CENTERS AS WELL AS OTHER FOUNDATIONS AND SO FORTH. IF WE'RE NOT BUILDING SOMETHING THAT'S VALUABLE TO YOU AN THAT YOU CAN ACTUALLY CARRY YOUR AGENDA FORWARD, THEN WE'RE GOING TO BE IN TROUBLE, AND AT THE SAME TIME, WE CAN'T BE ALL THINGS TO ALL PEOPLE, SO HOW DO WE BALANCE ALL THE NEEDS AND REQUIREMENTS AND CHANGE OUR PROTOCOLS OVER TIME TO ADD MORE AND MORE LAYERS OF SCIENTIFIC DISCOVERY THAT IT CAN ENABLE AS WE GO FORWARD. THESE ARE THE FUNDAMENTAL ELEMENTS OF IT, SO ALL OF THE DATA GOES TO A PUBLIC CLOUD ENVIRONMENT IN THE GOOGLE ENVIRONMENT, BUT THAT AWARD OF THE DATA AND RESEARCH CENTER. THIS IS ALL THE TOOLS THE RESEARCHERS WILL USE, ALL THE CLEANING AND CURATING OF THE DIE TA, AN AWARD TO VANDERBILT -- ALL OF THE BIOBANKING SAMPLES, RIGHT NOW I THINK THERE'S ABOUT 1.7 MILLION SPEAMS IN THE BIOBANK, BUT THAT'S AT THE MAYO CLINIC. THE PARTICIPANT KNOWLEDGE SYSTEM -- A PARTICIPANT PORTAL WHERE PEOPLE CAN INTERACT AND LOOK AT THEIR DATA AND ALL OF THAT AS WE BUILD THOSE TOOLS TO GIVE DATA BACK TO PEOPLE. WE HAVE PARTICIPANTS INVOLVED IN OUR GOVERNANCE FROM TOP DOWN, EVERY PLAYER HAS TO HAVE A PARTICIPANT ADVISORY BOARD INVOLVED ON WHAT THEY'RE DOING BEING AND WE'RE FOCUSED ON GETTING 75% UNDERREPRESENTED AND 50% AROUND A RACIAL -- WE DON'T HAVE THE SCIENCE OF DIVERSE COMMUNITIES AROUND THE COUNTRY AND THUS WE'RE OFTEN NOT INCLUDING THEM IN THE SCIENCE AND THEN THE CURE. SO THESE ARE AGGRESSIVE VERY STRONG GOALS AND COMMITMENTS TO ACHIEVING A VERY DIVERSE COHORT. WE'RE DOING THAT THROUGH THREE NETWORKS. WE HAVE A SET OF PARTNERS AROUND WHAT WE CALL THE DIRECT VOLUNTEER NETWORK. MANY PEOPLE COMING IN TO OUR PROGRAM ARE CALLING A 1800 NUMBER OR JOINING ALLOFUS.ORG, NOT AFFILIATED WITH BUT SAYING I WANT TO JOIN AND THEY CAN. THOSE PEOPLE MAY OR MAY NOT HAVE A DOCTOR, MAY OR MAY NOT HAVE INSURANCE, WE MAY NOT HAVE A PATH TO GET THEIR ELECTRONIC MEDICAL RECORD IN THE LONG TERM, BUT SOME OF THESE ARE NATIONAL PLAYERS LIKE QUEST, OR WALGREENS OR A COMPANY CALLED EMSI WHO DOES IN-HOME PHYSICALS FOR ALMOST EVERY MAJOR INSURANCE COMPANY AND CAN REACH LITERALLY EVERY ZIP CODE WITH A HOME VISIT FROM TRAINED CLINICIAN. I CAN'T AFFORD TO TURN ALL THAT CAPACITY ON IN THE COUNTRY AT ONE TIME BUT IN ADDITION TO THIS NETWORK OF HEALTH PROVIDER ORGANIZATIONS WHO ARE RECRUITING FROM THEIR PATIENTS, THESE DIRECT VOLUNTEER PARTNERS CAN SAY, HEY, WE'VE GOT THIS AREA OF THE COUNTRY, CAN YOU OPEN UP CAPACITY FOR SIX TO NINE MONTHS, WE HAVE A NETWORK OF NATIONAL AND LOCAL COMMUNITY PARTNERS AND WILL COME TO TOWN FOR SEVEN MONTHS TO BE ABLE TO PROCESS PEOPLE THROUGH AND GET THEM SOME TEMPORARY CAPABILITIES POPPED UP IN REMOTE AREAS, IN RURAL AREAS AND IN PLACES WHERE WE JUST DON'T HAVE A HEALTH PROVIDER ORGANIZATION WHO HAS APPLIED FOR OUR PROGRAM AND JOINED THAT EFFORT. SO THESE THREE COMMUNITIES ARE KEY TO US ACHIEVING NOT ONLY THE MILLION OR MORE BUT ALSO TO ACHIEVING THAT DIVERSITY. THESE ARE GRAND EXPERIMENTS, NOBODY'S REALLY DONE THIS AT QUITE THIS SCALE, BUT YOU CAN IMAGINE, IF WE FIGURE THIS OUT, SUDDENLY YOU HAVE THE ABILITY TO REACH PEOPLE WHO DON'T JUST HAPPEN TO LIVE NEAR AN ACADEMIC MEDICAL CENTER FOR SOME PRETTY INTENSE DATA CAP UR TOO, THEN IT COULD BE GAME CHANGING FOR HOW WE APPROACH THIS. IT'S A BIG EXPERIMENT, WE'VE GOT A LONG WAY TO GO AS WE GET THERE. THIS IS THE VERSION 1 PROTOCOL. WHAT I TELL PEOPLE IS, HEY, THIS IS VERSION 1, I THINK OF IT AS A NEW APPLE UPDATE. IF WE CAN GET PEOPLE THAT EXCITED ABOUT, HEY, IN FOUR YEARS WE'RE RELEASING VERSION 2 OF THE ALL-OF-US RESEARCH PROTOCOL AND IT'S GOING TO FOCUS ON THESE PROBLEMS AND AREAS, THAT WOULD BE REALLY EXCITING. SO FOR VERSION 1, THIS IS BASICALLY RIGHT NOW WE'RE RECRUITING 18 AND ABOVE, WE'RE WORKING ON OUR PLANS FOR CHILDREN AND OTHER SPECIAL POPULATIONS AND HOPE TO AT LEAST START WITH ZERO TO SIX YEARS OF AGE IN ABOUT SUMMER NEXT YEAR. THERE'S AN ONLINE INTERACTIVE CONSENT OR PEOPLE WALKING THROUGH THAT CONSENT PROCESS IF THEY CAN'T DO THAT FOR THEMSELVES. WE PAY A LOT OF ATTENTION TO INFORMEDNESS. I'VE BEEN PART OF 17 CLINICAL TRIALS AND STUDIES, I'VE NEVER, EVER GOTTEN MY OWN DATA BACK AND THE ONES THAT SAY I'M GOING TO SHARE YOUR EHR DATABASEICALLY SAY CLICK HERE TO SHARE YOUR EHR DATA. THEY NEVER REALLY TOLD ME WHAT'S IN MY EHR. SO THROUGH VIDEO ANIMATIONS WITH LANGUAGE DOWN TO FIFTH GRADE READING LEVELS, WE'RE HELPING PEOPLE UNDERSTAND WHAT THE TRUE RISKS ARE. WE'LL PROBABLY WRITE SOME PAPERS SOON ABOUT JUST WHAT WE'RE LEARNING AND IT MEANS WE LOSE SOME PEOPLE BUT I WOULD RATHER DO THAT THAN HAVE THEM WALK IN HERE AND NOT KNOW WHAT THEY'RE SIGNING UP FOR. THERE ARE THREE INITIAL SURVEYS, THE BASE,, OVERALL HEALTH AND PERSONAL HABITS, HEALTHCARE ACCESS AND UTILIZATION HAVE BEEN RELEASED, SO IF YOU'VE BEEN IN THE PROGRAM FOR A WHILE, AFTER LIKE 90 DAYS AND YOU'VE DONE ALL THE OTHERS, YOU'LL BE INVITED TO DO THAT. FAMILY MEDICAL HISTORY, WE'RE ABOUT TO HAVE PERSONAL HEALTH HISTORY LAUNCH. ALL OF THESE, WE'RE NOT INVENTING OURSELVES, WE'RE LEVERAGING INSTITUTES AND CENTERS AND OA BUT OFTEN FOR A LOT OF THE LANGUAGE, WE'RE HAVING TO DO WORK TO BOTH REDUCE IT AND GET IT DOWN TO THE FIFTH GRADE READING LEVEL AND ALSO TRANSLATE INITIALLY TO SPANISH. WE HAVE OTHER LANGUAGES BUT RIGHT NOW EVERYTHING IS IN ENGLISH AND SPANISH. BASIC PHYSICAL MEASUREMENTS. IF WE HAD 10 MILLION PEOPLE SIGN UP, WE DON'T HAVE THE THE FUNDS TO GO IN AND ACTUALLY SAY WE CAN DO 10 MILLION EHR RECORDS AND WHOLE GENOME SEQUENCES SO WE HAVE TO SELECT, AND OUR SELECTION CRITERIA ARE AROUND DIVERSITY OF GEOGRAPHY, DIVERSITY OF DEMOGRAPHICS, AND THEN DIVERSITY OF HEALTH STATUS. BUT IF YOU'RE INVITED TO COME DO PHYSICAL MEASUREMENTS, IT'S NO THE A PHYSICAL, I'VE HAD PEOPLE START TO SAY, WHAT IF, YOU KNOW, SOMEBODY SEES THAT THE WOMAN HAS A BREAST TUMOR? IT'S LIKE, SHE'S GOING TO HAVE HER CLOTHES ON, THIS IS NOT REPLACING THE PHYSICAL WITH YOUR DOCTOR, RIGHT? SO IT'S BMI, HEART RATE, HEIGHT, HIP CIRCUMFERENCE AND WEIGHT, A BLOOD AND A URINE SAMPLE. IF YOU WANT ALL THE DETAILS, THE WHOLE PROTOCOL IS ON OUR WEBSITE SWELTS AS WELL AS HOW MANY TUBES THIS IS SPLIT INTO, THE DIFFERENT TUBES, THE BIOBANK FOLKS ARE VERY GOO AT EXPLAINING THAT, AND THEN WE'RE WORKING ON THINGS WITH WEARABLES. WE'RE ALREADY DOING SOME PILOTING WORK WITH FITBIT, YOU'LL SEE SOME OTHER ANNOUNCEMENTS SOON. FOR THE FIRST PHASE, IT'S A BRING YOUR OWN DEVICE PHASE AND WE'LL PROBABLY DO THIS FOR A COUPLE OF YEARS. AT SOME POINT, WE'LL NEED TO FIGURE OUT WHETHER THE CONSUMER MARKET ITSELF IS GOING TO HAVE THE CAPABILITIES WE NEED TO ANSWER THE SCIENTIFIC QUESTIONS OR DO WE NEED TO HAVE SOMETHING BUILT AS THE WEARABLE FOR THE ALL-OF-US RESEARCH PROGRAM. THIS IS AN AREA THAT I FUNDED A LOT OF RESEARCH ON IN MY PREVIOUS LIFE AND KNOW A LOT ABOUT, AND YES, WE ARE, WOULDING ON SOME OF THOSE DONATIONS SO THAT WE CAN GIVE THEM TO PEOPLE WHO DON'T HAVE THEM, BUT RIGHT NOW I THINK IT WILL BE YEARS BEFORE WE MAKE A DECISION ABOUT WHAT'S THE WEARABLE DEVICE THAT WE'RE GOING TO PUT IN PLACE FOR ALL MILLION PEOPLE AND WE'RE GOING TO LEARN FROM WHAT'S ALREADY OUT THERE FIRST BEFORE WE GET TO THAT POINT. SO THIS IS THE BASICS, WE STARTED SOME OF THESE OTHER EFFORTS. I JUST DID A CONGRESSIONAL BRIEFING FOR STAFFERS THIS MORNING AND I TOLD THEM I PREDICT THAT THE COST ULTIMATELY OF WHAT IT TAKES TO GET A HIGH QUALITY COMPLETE ELECTRONIC HEALTH -- OR AS COMPLETE AS POSSIBLE ELECTRONIC HEALTH RECORD WILL BY FAR SUPERSEDE THE COST OF WHAT IT'S GOING TO TAKE TO GET GENETICS AND WHOLE GENOME SEQUENCING. RIGHT NOW IT'S HARD FOR ME TO SAY THAT, GIVEN THE PRICING I'VE SEEM COME IN FOR OUR GENOME CENTERS, BUT I THINK THAT CHALLENGE, CURATING THAT DATA, MAKING IT RESEARCH-READY, WILL END UP BEING OUR BIGGEST COST IN TERMS OF TECHNOLOGY. I THINK OUR TRUE BIGGEST COST IS RECRUITING, MAINTAINING AND RETAINING THOSE RELATIONSHIPS FOR THE LIFELONG PART OF THE STUDY. WE LAUNCHED NATIONALLY MAY 6TH. WE DID A YEARLONG BETA PHASE AS DIFFERENT CLINIC SITES. WE HAVE AS OF TODAY 105,000 PEOPLE WHO HAVE SIGNED UP AND ARE SOMEWHERE IN THE PROCESS. 55,000 OF THOSE HAVE FINISHED THAT WHOLE VERSION 1 PROTOCOL AND WE'RE RUNNING AT ABOUT 77% OF THAT 55,000 WHO ARE UNDERREPRESENTED IN BIOMEDICAL RESEARCH, WHICH IS PRETTY DARN& GOOD. YOU CAN IMAGINE SOME OF OUR PARTNERS WERE LIKE, LET'S JUST SEE WHO WE GET AND WE'LL FOE FOCUS ON DIVERSITY LATER. IF YOU DON'T FOCUS THAT FROM THE BEGINNING, WE WILL NEVER CATCH UP WITH THE GAP THAT WE WILL CREATE FOR OURSELVES. SO I THINK THOSE NUMBERS WILL DIP AT TIMES AND WE'LL BE LIKE, OKAY, WE'VE GOT TO ADJUST, AN THERE WAS SO LITTLE LITERATURE THAT COULD REALLY GUIDE US ON ANYTHING AT THIS SCALE THAT WE'RE HAVING TO DO A LOT OF INVENTING AND TESTING ON OUR OWN AS WE MOVE FORWARD IN TIME. SO WE LAUNCHED IN SEVEN VERY DIFFERENT COMMUNITIES AROUND THE COUNTRY, ALL IN A SIEM YOU CAST ON MAY 6 AFTER THAT BETA PHASE AND NOW WE'VE GOT PEOPLE COMING IN FROM ALL 50 STATES, EVEN THOUGH WE DON'T HAVE THE ABILITY TO DO BIOSPECIMEN CAPTURE IN ALL 50 SPEIGHTS, WE'RE 50 STATES. WE'RE JUST STARTING TO TEST THIS THING CALLED BURST OR POP-UP CAPACITY WITH OUR VOLUNTEER PARTNERS. SO LET'S GO INTO AN AREA WHERE WE DON'T KNOW ANYTHING HOW DO WE DO THE RIGHT MARKETING AND AWARENESS AND BUILD RELATIONSHIPS WITH PEOPLE, AND THEN HOW DO WE PUT THAT CAPACITY UP TO COME AND CATCH QUALITY SAMPLES DURING THAT PERIOD OF TIME AND WHAT EAR WHAT OTHER EVENTS OF VALUE CAN WE DO FOR THAT COMMUNITY AS WE GO THROUGH. SO IN LESS THAN TWO YEARS, WE DEVELOPED AND UPDATED THE PROTOCOL, BUILT THESE NETWORKS, 200 CLINICS, 20 STATES, GROWING ARE MO OF THOSE. THE BIOBANK IS DOING A 24-HOUR SHIPPING PROCESS. WE'RE TRYING TO DO AS MANY NIGHTS AND WEEKENDS LOCATIONS AS POSSIBLE. THE CHALLENGE RIGHT NOW IS GETTING THOSE SAMPLES WITHIN THE 24-HOUR WINDOW TO THE BIOBANK, ESPECIALLY ON THE WEST COAST. WE'RE HAVING HUGE PROBLEMS WITH COURIERS AND THE TOTAL COST PER PERSON, SO WE'RE GOING TO HAVE TO SORT OF DEAL WITH THAT PROBLEM AND FIGURE OUT STRATEGIES FOR THAT OVER TIME. THE LAST THING I WOULD JUST SORT OF TALK A LITTLE ABOUT, PEOPLE ARE LIKE WHEN ARE YOU GOING TO RELEASE THE RESEARCH DATA? WHEN IT'S READY. I MEAN THAT IN ALL SERIOUSNESS. WE'VE CLEANED IT AND CURATED THE DATA AND MADE SURE IT IS WHAT IT SAYS IT IS BUT RIGHT NOW I'M LIKE, FOLKS, WE ARE AT THE TI KNEE FIRST STEPS OF A LONG, LONG JOURNEY, AND IF WE DON'T GO BACK TO THAT FIRST STRATEGIC OBJECTIVE OF BUILDING TRUST AND GETTING THEM ENGAGED, THERE WON'T BE ANY DATA OR SUSTAINED DATA, SO WE'RE TRYING TO BALANCE THIS. OUR CURRENT PLAN IS WE WOULD OPEN A PUBLIC DATA BROWSER OPEN TO LITERALLY ANYBODY WITHOUT A LOG-IN WHERE YOU COULD AT LEAST GET GENERAL CHARACTERISTICS ABOUT THE COHORT THAT WE HAVE PROBABLY -- HOPEFULLY AS A CHRISTMAS PRESENT TO ALL OF US THIS YEAR. RIGHT NOW WE'RE TARGETING SORT OF MID SUMMER OR SO NEXT YEAR FOR THE RELEASE OF THE FIRST CURE AITD DATA REPOSITORY, BUT I MAY CHANGE THAT SIGNIFICANTLY BECAUSE IF WE DECIDE OUR CHILDREN PROTOCOL NEEDS SOME FUNDAMENTAL NEW CAPABILITY THAT WE'RE NOT DOING FOR THE ADULTS, THEN IT'S LIKE, OH, THERE'S A LEAD TIME TO BUY THAT EQUIP MENT, PUT IT INTO THE BIOBANK AND TEST IT, SO I'VE GOT SOME BIG CAVEATS HERE ON DOING THAT, BUT IN GENERAL, WE WANT TO GET THE DATA OUT. THERE ARE PEOPLE ON OUR ADVISORY PANEL FROM THE U.K. BIOBANK THAT SAYS COLLECT THE DATA FOR SEVEN YEARS AND DON'T GIVE ANYBODY ANY DATA UNTIL THE END OF THAT. I'M LIKE, THAT'S NOT POLITICALLY VIABLE IN THE WORLD IN WHICH WE LIVE AND I WOULDN'T WANT THAT, WE WANT THE SCIENTIFIC COMMUNITY ENGAGING ALL THE WAY THROUGHOUT, BUT AT THE SAME TIME, I'M LIKE FIRST THINGS FIRST, BUILD THOSE RELATIONSHIPS, START CATCHING QUALITY DATA, THE CHALLENGES OF CURATION AND ALL THAT CAN WAIT A LITTLE BIT IF WE NEED TO PUSH THAT OUT A LITTLE BIT. I'M HOPING BY SUMMER OF NEXT YEAR, THAT'S THE BEGINNING OF RELEASES OVER TIME AS WE GO THROUGH. SO I DON'T KNOW WHERE I AM IN TIME, I'M PROBABLY LOST IN TIME AS USUAL. I HAD OTHER SLIDES I COULD SORT OF TALK ABOUT BUT I WON'T. LET ME JUST SOP IT STOP IT THERE AND OPEN IT UP FOR ANY QUESTIONS, AND I'LL STAY AS LONG US A LIKE IN THE NORA KICKS ME OUT. [APPLAUSE] >> YOU SHOULD NEVER SAY THAT, I'LL KEEP YOU HERE FOREVER! >> THANKS SO MUCH, REPLI APPRECIATE YOUR ENERGY AROUND THIS TOO, IT'S FANTASTIC. DEFINITELY WANT TO SUPPORT YOUR RECRUITMENT STRATEGY ABOUT STARTING AT THE BEGINNING WITH DIVERSITY RATHER THAN MAKING IT AN ADD-ON. THAT'S HUGELY IMPORTANT AND VERY OFTEN NOD DONE. NOT DONE. IF I'M A REGULAR PERSON OUT THERE, I HEAR ABOUT THIS PROJECT, I PROBABLY THINK IT'S GOING TO BE A LITTLE LIKE 23 ME OR SOMETHING WHERE I'M GOING TO GIVE YOU SOMETHING AND I'M GOING TO IMMEDIATELY KNOW SOMETHING ABOUT MYSELF. IS THAT WHAT'S GOING TO HAPPEN? WHAT IS THE INDIVIDUAL WHO'S PARTICIPATING -- AND WHAT -- WHEN AND WHAT ARE THEY GETTING? >> ONE OTHER CONGRESSWOMAN ASKED ME THIS MORNING WHAT'S MY BIGGEST CHALLENGE? HONESTLY, IT'S EXPECTATION MANAGEMENT WITH ALL OF OUR STAKEHOLDERS. AND PARTICULARLY WITH PARTICIPANTS. THE NUMBER OF INTERVIEWS I'VE HAD TO DO AS A RESULT OF THE GOLDEN -- WHATEVER THE GUY WAS CALLED, THAT THEY CAUGHT THROUGH THAT TEST, THE NUMBER OF EVEN SCIENTIFIC PRESS WHO SHOULD KNOW BETTER WHO THEN SAID ALL-OF-US EQUALS 23 AND ME AND IT'S LIKE, LET'S SEE. NO, WE'RE NOT THE SAME, WE'RE A FEDERALLY PROTECTED RESEARCH, THERE ARE LAWS CALLED CERTIFICATES OF CONFIDENTIALITY THAT WERE BEEFED UP IN THE 21ST CENTURY CURES BILL THAT WE FOUGHT FOR THAT MADE CERTIFICATES OF CONFIDENTIALITY MANDATORY, SO IT WILL TAKE US LONGER TO GIVE THAT INFORMATION BACK TO PARTICIPANTS, AND BLUNTLY I WILL TELL YOU, AS WE APPROACH SOME OF THE VENDORS, I DON'T WANT NIH TO MEAN "NOT INVENTED HERE." I'D FAR RATHER LEVERAGE COMMERCIAL THINGS THAT ARE OUT THERE, BUT IF THEY'RE NOT GOING TO PLAY BY OUR DATA USE RULES, MANY OF THEM ARE LIKE, WELL, WE WANT THE ACTUAL DATA AND WE WANT TO BE ABLE TO SELL IT AND ALL OF THAT, AND I'M LIKE, NO, AND THEN A LOT OF THEM ARE LIKE, HEY, UH, WE WANT FIRST DIBS ON THE DATA. IEN LIKE, WE'RE NOT EVEN LETTING OUR OWN CONSORTIUM P.I.s HAVE FIRST DIBS OUTSIDE OF DEMONSTRATION PROJECTS JUST TO PROVE TO US THAT THE DATA IS VALID AND USEFUL FOR WHAT HE WITH SAY IT IS. SO THOSE ARE SOME OF OUR CHALLENGES IN THAT REGARD. AND WHAT WE'RE TRYING DO AND COMMUNICATE VERY OPENLY AND TRANSPARENTLY WITH OUR PARTICIPANTS IS LIKE, THERE'S GOING TO BE MORE VALUE FOUR OVER TIME. WE'RE ABOUT TO RELEASE SIMPLE COMPARATIVE SURVEYS SO THAT US A FILL OUT YOUR SURVEY OR AFTER YOU FILL IT OUT, YOU CAN AT LEAST COMPARE YOURSELF TO THE COHORT AND I THINK THE -- DATA EVENTUALLY. IT'S ACTUALLY PRETTY HARD TO DO. SO IT'S LIKE, NO, YOU'RE NOT GOING TO IMMEDIATELY SORT OF GET BACK WHAT YOU WOULD GET WITH 23 AND ME, BUT AT THE SAME TIME, FOR OUR GENOME CENTERS, WE'RE GOING TO DO -- FOR ALL MILLION, WE'RE GOING TO DO GENOTYPING AND WHOLE GENOME SEQUENCING AND WE HAVE COMMITTED TO GIVING ANCESTRY DATA BACK, BUT RIGHT NOW WE'RE FOCUSING ON THE HARDER PROBLEMS OF HOW DO OH YOU GIVE PATHOGENIC VARIANT INFORMATION BACK TO PEOPLE IN APPROPRIATE WAYS, ESPECIALLY IF THEY HAVE NO DOCTOR WHATSOEVER, AND YOU'LL SEE OUR AWARDS ABOUT TO COME OUT FOR GENETIC COUNSELING RESOURCE. I DON'T KNOW WHAT THE RESPONSE TO THAT IS GOING TO BE. EVEN SOME OF OUR TOP END HEALTH PROVIDER ORGANIZATION ON THE CUTTING EDGE OF PRECISION MEDICINE ARE LIKE, YOU CAN'T USE THE COUNSELORS BECAUSE THEY'RE TAXED COMPLETELY WITH THE CLINICAL COUNSELING WE NEED TO DO. SO THERE'S A ROAD MAP OF VALUE THAT WE'RE TALKING TO OUR PARTICIPANTS ABOUT. YOU DON'T WANT TO TAKE IT SO FAR THAT IT'S BECOMING COIR SIEVE, THE IRB IS REALLY SENSITIVE TO THAT AND SHOULD BE, AT THE SAME TIME WE'RE TRYING TO GET THEM UNDERSTAND THE LONGER YOU'RE IN, THE MORE MEANINGFUL THE DATA WILL BE TO BOTH YOU AND OTHER TOOLS. BUT STARTING CERTAINLY BY NEXT SUMMER THIS TIME, I WOULD EXPECT US TO HAVE HAD THE RETURN OF SOME EHR DATA AND ALL OF THAT TO PARTICIPANTS AND WE'LL BE WELL ON OUR PATH TO PILOTING THE RETURN OF GENOME DATA AND SOME OF THE WHOLE GEE NO, MA'AM SEQUENCING DATA. WE'RE PIE LOGHT RETURN OF RESULTS OF THE MORE COMPLICATED CLINICALLY ORIENTED RESULTS WITH 20,000 OF OUR PARTICIPANTS CHOSEN VERY DIVERSELY AND SOME COMPARATIVE METHODS TO SEE HOW TO DO THAT BECAUSE ONCE AGAIN, WE REACHED OUT TO TOP PEOPLE DOING THIS AND THEY'VE GIVEN US GREAT INFORMATION BUT ALMOST NONE OF THEM ARE DOING IT ACROSS THIS SCALE ACROSS THE COUNTRY, AND WE'RE LIKE, OWE KAI YOU DID IT FOR BOSTON BUT BOSTON IS KIND OF UNIQUE IN THE AREA OF GENOMICS, PROBABLY KANSAS CITY IS NOT THE SAME AS BOSTON, SO HOW ARE WE GOING TO DO THAT. >> THANKS VERY MUCH. REALLY ENJOYED YOUR PRESENTATION, AND KUDOS TO YOU IN YOUR PROFESSIONAL LIFE AND YOUR PERSONAL LIFE COLLIDE, YOU MADE LEMONADE OUT OF LEMONS. I KNOW SOMETHING ABOUT THAT TOO SO I'LL SEND YOU A SEPARATE EMAIL, MOST OF PEOPLE HERE KNOW IT. I'M REALLY STRUCK BY THE FACT THAT THIS IS WHAT YOU'RE DOING IS IMPLEMENTATION SCIENCE. AND MANY OF US AROUND THIS ROOM HAVE STRUGGLED WITH TRYING TO CONVEY THIS TO THE POPULOUS AND OTHER RESEARCHERS WHO KIND OF CONFUSE THE UNIT OF ANALYSIS, AND SO YOU COULD ACTUALLY DO THE SCIENCE OF THE SCIENCE, RIGHT? AND YOU COULD COULD COULD RESEARCH THE PROCESS, ROLL THIS OUT, BROKE IT INTO STEPS AS TO WHAT YOU WOULD DO NOW IF YOU KNEW THEN, THAT KIND OF THING. I WAS WONDERING IF YOU ACTUALLY ARE GOING TO BE PUBLISHING SOME OF THIS PROCESS SO THAT YOU CAN SHOW US -- >> WHAT I KEEP HEARING FROM PEOPLE IS, LIKE, EVEN WHAT YOU JUST SAID WOULD BE NEWS AND I'M LIKE, OH, SO I WAS JOKING, I SAID, I NEED TO HIRE ONE OF MY MEDICAL ANTHROPOLOGIST FRIENDS JUST TO COME IN AND STUDY US AND OUR DECISION-MAKING, AND THEN ALSO ASK SOMEBODY TO PUT SOME AWARDS OUT THAT CAN STUDY US IN THE PROCESS THAT WE'RE DOING. WE ARE MAKING DECISIONS AS WELL INFORMED WE CAN BUT WE'RE TRYING TO MAKE THEM QUICKLY AND I FEAR THAT WE'RE LOSING SOME -- WE HAD GOOD REASONS FOR NOT DOING THINGS AND PARTICULARLY WHEN WE'VE TRIED THEM. I THINK CERTAINLY WITH THE DESIGN OF THE RETURN OF GENETIC INFORMATION AND DET DESIGN OF SOME OF OUR APPROACHES WE'RE DOING WITH MESSAGING AND MARKETING FOR DIVERSE COMMUNITIES, THAT IS BEING -- WE NOW HAVE THE INFRASTRUCTURE IN PLACE TO DO THOSE AS MORE PROPER COMPARATIVE STUDIES AND WE'LL BE ABLE TO PUBLISH MORE OF THOSE. BUT I'VE BEEN BUGGING MY TEAM SAYING EVEN BEFORE YOU DO THE PEER REVIEWED PAPERS, I THINK WE OUGHT TO OPEN UP SOME BLOGS WHERE PEOPLE ARE JUST TALKING ABOUT THE STRUGGLES AND THEN THE CHOICES WE MADE, IN THE SPIRIT OF TRANSPAREN Z BUT ALSO TRANSPARENCY, FOL KS LIKE THE MILLION VETERANS PROGRAM HAVE BEEN GIVING US VERY PRACTICAL KNOWLEDGE, SO WE REACH OUT TO THESE OTHER COHORTS, BUT A LOT OF THEM HAVEN'T DONE COMPLETELY OPEN DATA FOR RESEARCHERS SO THEY'RE NOT DEALING WITH THE SAME DEIDENTIFICATION THAT WE ARE AND ALMOST NONE ARE DOING RETURN OF INFORMATION LIKE THIS. WE'RE LIKE, WE DON'T EVEN HAVE PARTICIPANT ADVISORY BOARD, WE CAN'T HELP YOU ON THAT ONE SO IT'S LIKE, ALL RIGHT, WE'LL FIGURE IT OUT. >> IS THERE A CENTRAL LAB THAT& DOES ALL THE GENETIC ANALYSIS LIKE FOR ALL 1 MILLION SAMPLES? >> YEAH, SO WE PUT OUT A CALL, AND WE ARE EVALUATING AND YOU'LL SOON HEAR THE RESULTS FOR THE GENOME CENTERS THAT ARE DOING THE GENOTYPING AND WHOLE GENOME, AND WE SET IN A CALL ONE TO TWO INITIAL CENTERS. YOU'LL SEE THAT ANNOUNCEMENT. THEN THE FUNDING ANOWSMENT IS COMING OUT SOON FOR THE GENETIC COUNSELING RESOURCE AND THEN WE'LL SEE WHAT WE GET AND HAVE TO REVIEW ALL OF THOSE. BUT IT WON'T BE ONE PLACE. WE'LL WANT PLACES TO DO CROSS VALIDATION OF ONE ANOTHER, BOTH IN TERMS OF DATA QUALITY, ACMG VARIANTS THAT COME BACK, ANOTHER LAB THAT THEN RUNS ADDITIONAL BEFORE WE RETURN THAT INFORMATION FOR THOSE 1 TO 2% THAT WOULD HAVE A KNOWN PATHOGENIC VARIANT. SO IT'S GOING TO CERTAINLY TAKE MORE THAN ONE CENTER TO BE ABLE TO PULL THAT OFF. >> I WAS WONDERING ABOUT THAT JUST BECAUSE WE HAVE THE ABCD STUDY WITH SUCH A BIG COHORT ALSO THAT WE WOULD NEED -- ARE THEY GOING TO OPTIMIZE IT AND STANDARDIZE IT SO RIGOROUSLY THAT MAY BE GOOD TO USE THE SAME LAB? >> NORA AND I HAVE ALREADY HAD PART OF THAT CONVERSATION AND, YOU KNOW, I THINK FROM MY POINT OF VIEW, I'M TRYING TO SORT OF REACH OUT TO INSTITUTES AND CENTERS LIKE, LOOK, IF YOU'VE ALREADY GOT A KNOWN WAY OF DOING SOMETHING, WE'LL JUST GO LEVERAGE YOURS AND IF WE'RE DOING SOMETHING THAT CAN HELP YOU WITH WHAT YOU'RE DOING. I GET A LITTLE NERVOUS BECAUSE PEOPLE ARE LIKE LOOK, BY YOUR SHEER SIZE, YOU'RE GOING TO START TO DRIVE STANDARDS. I'M LIKE, OH, MY GOD, LET US MESS UP A LITTLE MORE BEFORE YOU'RE COPYING US AS STANDARDS. ALL WE'RE DOING IS TRY AND LESH, TRY AND LEARN, PEOPLE HAVE DONE IT ON SMALL SCALE, BUT WHEN A STUDY SHOWS YOU HEY, WE RECRUITED 300 REALLY DIVERSE PEOPLE, KEPT THEM -- AND IT TOOK TWO FT Es AND I'M LIKE THAT IS GREAT BUT NOT FOR A MILLION PEOPLE. >> LONGITUDINAL STUDY FOR 15 YEARS, HOW OFTEN DO YOU COLLECT THE BLOOD AND URINE SAMPLES? AND I PRESUME THE URINE IS GOING TO BE MET BLOWME TAB -- >> WE ARE CAPTURING THE BLOOD AND URINE -- WE JUST MADE A CHANGE IN THE WAY WE WERE ACTUALLY DOING OUR TUBES TO GET -- YOU'LL HAVE TO CORRECT ME, I KNOW IT'S BIC PLIK BUT CIRCULATING FREE SELL DNA OR WHATEVER THE HECK IT'S CALLED, SO OUR TUBES HAVE CHANGED SO WE CAN SORT OF MAKE SURE WE GET THAT IN THE RIGHT WAY. THE FREQUENCY IS GOING TO DEPEND ON -- SO WEE GONE THROUGH A SCIENTIFIC REQUIREMENTS GATHERING PROCESS THAT NIH HAS BEEN INCREDIBLY HELPFUL ON WHERE WE'VE BEEN GATHERING REQUIREMENTS FROM PEOPLE OF LIKE WHAT WOULD YOU LIKE TO AIM THIS RESOURCE AT, AND WHAT WE'RE LOOKING FOR ARE A LOT OF CAPABILITIES THAT WOULD SERVE MULTIPLE AREAS OF SCIENCE. AND THEN ONES THAT CAN SCALE IN A DATA QUALITY-DRIVEN WAY, AND OUTSIDE OF THAT THEN, IF IT'S ONE THAT'S SO UNIQUE TO A PARTICULAR DISEASE OR INSTITUTE, INVITING THEM TO PROPOSE ANCILLARY STUDIES, TO DO THAT PARTICULAR THING. SO WE ARE WORKING ON OUR SORT OF ENVIRONMENTAL PLAN SO HE WITH HAVE COMBINATIONS OF WHAT WE'RE GOING TO CAPTURE. WE'RE ABOUT TO DO A BUY PAI LOT OF PILOT ASSAYING, BUT CAN I THINK WE'LL DO A COUPLE PILOTS ON ASSAY APPROACHES, THE ONES WE'RE GOING TO PAY FOR FOR ALL MILLION PEOPLE, AND OBVIOUSLY PEOPLE WILL APPLY TO USE THE COHORT FOR SOME STUDIES OR ACTUALLY GET ACCESS TO THE SAMPLES RIECHT SAM SAMPLES. WE'RE WORK THROUGH OUR COMMITTEES AND OUR IRB, WE'RE NOT REALLY READY, BUT WE'LL MAKE DATA AVAILABLE HOPEFULLY MID NEXT SUMMER BUT I DON'T THINK IT WILL NECESSARILY BE SAMPLES YET. WE'LL HAVE TO STILL WORK OUT THE LOGISTICS OF THAT AS WE GO. >> WHY NOT FECAL SAMPLES? >> BECAUSE WE GOT FEEDBACK FROM OUR PARTICIPANTS THAT IT'S LIKE, YOU WANT TO WALK DOWN THAT ROAD, YOU'D BETTER DO SOME OTHER THINGS WITH US FIRST, BUT WE'RE VERY INTERESTED IN THE MICROBIOME. WE HAD LISTENING SESSIONS EVEN BEFORE THE PROGRAM EXISTED AND BELIEVE ME, I'M REALLY INTERESTED IN IT SIEBTIVEICALLY AS SCIENTIFICALLY AS WELL BUT THIS IS LIKE BACK TO BUILD THAT TRUST. YOU'VE GOT TO REMEMBER, SOME OF THE PEOPLE IN OUR PROGRAM HAD BEEN IN OTHER -- WE DID NOT HAVE ENOUGH FREQUENTLY ASKED QUESTIONS AT LAUNCH ABOUT WHAT IS RESEARCH, WHAT DOES THE WORD BIOMEDICAL MEAN. SO IF WE'RE GOING TO REALLY BE TRUE TO THOSE COMMUNITIES, WE'VE GOT TO BUILD THAT TRUST AND RELATIONSHIP AND GO FOR SOME OF THOSE THINGS LATER. WE'RE NOT DOING HAIR OR FINGERNAIL INITIALLY, BUT WE COULD SAVE THOSE FOR VERSION 2 PROTOCOL. ARE WHAT ARE WE GOING TO CAPTURE AGAIN, WHAT WAS A UNIQUE ONE-TIME THING, AND THERE'S LOTS OF DEBATES ABOUT THAT IN OUR CONSORTIUM. IT'S ALL IN THE HR. YOU SHOULDN'T TRUST THE EHR AT ALL! IT'S JUST LIKE, OKAY, LET'S COME TOGETHER AND FIGURE OUT SOME MIDDLE GROUND. >> ERIC, IT'S JUST AMAZING, THERE ARE SO MANY THINGS ONE CAN LEARN FROM HOW DO YOU COMMUNICATE, HOW DO YOU ENGAGE, HOW DO YOU GENERATE TRUST. BUT THERE'S SOMETHING TOO THAT JUST JUMPED, WE WERE DISCUSSING THE ISSUE OF PERSONALIZED MED SON BUT WHAT YOU ALSO ARE LIKELY TO BE ABLE TO DWELL ON IS THE SYSTEMS THEMSELVES, BECAUSE YOU'RE GOING TO HAVE PROSPECTIVE DATA, AND WE ARE AT THE STATE IN HEALTHCARE WHERE WE CANNOT KEEP THE RATE THE WAY THAT WE ARE DOING HEALTHCARE BECAUSE IT'S NOT SUSTAINABLE. SO HOW DO YOU GENERATE NEW MODELS WITH THOSE GIGANTIC COSTS? SO HOW ARE YOU GOING TO INCORPORATE THE INFORMATION REGARDING TO THE QUALITY AND THE SYSTEM THAT THE PARTICIPANTS ARE GETTING? >> IT'S REALLY FUNNY THAT YOU ASK THAT BECAUSE I'VE BEEN ASK ASKING EVEN IN MY INTEL WORLD, WE WERE DOING ETHNOGRAPHIC STUDIES IN 50 COUNTRIES AROUND THE WORLD AND WE WERE LIKE WE NEED A NOMENCLATURE BY WHICH WE CAN NAME THESE THINGS AND COMPARE THEM, AND WE WANTED TO ASSOCIATE THEM WITH IT. ONE OF THE THINGS I ASKED OUR HEALTHCARE UTILIZATION TEAM IS DO YOU HAVE ANY KIND OF SEGMENTATION MODEL SO WE CAN CAPTURE WHAT KIND OF CARE PARADIGM ARE PEOPLE IN? AND TRY TO START TO GET AT THOSE SETTINGS. I HAVE NOT FOUND A GREAT EXISTING SEGMENTATION MODEL THAT COMPARES THE SORT OF CARE PARADIGMS THAT YOU'RE IN, BUT I THINK WE CAN AT LEAST START COLLECTING SOME, QUOTE-UNQUOTE, METADATA ABOUT -- AND GETTING FROM PETE PEEM AN PEOPLE AN UNDERSTANDING OF CONDITIONS OF THEIR CARE THAT COULD LEAD TO AT LEAST A QUALITATIVE SEGMENTATION THAT TREATS THE CARE SYSTEM THAT YOU'RE IN AS VARIABLE IN AND OF ITSELF. WHICH I THINK WOULD BE REALLY FASCINATING, BUT IF YOU LOOK AT LARGE EMPLOYER DATABASE, IT WAS REALLY HARD TO COMPARE THE INTEL PARADIGM OF CARE TO THE GOOGLE PARADIGM OF CARE AND WE WERE DOING SOME OF THE MOST INNOVATIVE MODELS ON THE PLANET. WHAT ARE THE VARIABLES THAT MATTER THAT YOU WOULD WANT TO CAPTURE THAT YOU WOULD KNOW ABOUT THE SYSTEM OF CARE THAT YOU COULD THEN COMPARE LATER ON AS YOU GO THROUGH IT. >> BUT BECAUSE YOU'RE SWIMMING IN AN UNSWUM OCEAN -- >> THAT'S ANOTHER ONE, JUST SET THE STANDARD. I ASKED FOR THE SAME THING FOR AN ENVIRONMENTAL SEGMENTATION, BECAUSE WE WANT GEOGRAPHIC DIVERSITY FOR DIFFERENT EXPOSOMES SO I WAS LIKE SURELY YOU GUYS HAVE A SEGMENTATION MODEL THAT TELLS US THESE ARE THE 40 QUADRANTS OF THE COUNTRY YOU NEED TO MAKE SURE YOU COVER. AND WHILE THEY EXISTED FOR LIKE ONE POLLUTANT VERSUS ANOTHER, THERE WAS NO GENERAL THAT SAYS WELL WHAT WOULD BE THE CRITERIA WE WOULD USE TO MAKE SURE THAT WE'VE GOT GEOGRAPHIC DIVERSITY FROM THE STANDPOINT OF EXPOSOME, BOTH SOCIAL AND PHYSICAL, AND THEY'RE LIKE, YOU SHOULD MAKE ONE. AND I'M LIKE, OKAY, RIGHT NOW WE'RE JUST GOING TO TRY TO RECRUIT PEOPLE, WE'RE A STARTUP WE'RE TRYING TO RECRUIT PEOPLE. BUT I DO THINK YOU'RE ON TO SOMETHING THAT COULD BE BOTH DISCOVERABLE -- I THINK WHEN YOU RUN BIG DATA ANALYSIS ON THESE THINGS, YOU WILL COME UP WITH GOOD HYPOTHESES THAT CAN BE TESTED IN WAYS CARRYING FORWARD THAT YOU'D BE LIKE, OH, YOU'LL SEE SOME INTERESTING CLUSTER ANALYSIS AND THEN BE LIKE, OKAY, LET'S THE START WITH THAT AS YOUR SEGMENTATION MODEL AND THEN START TO SEE IF IT BEARS OUT IN TIME, AND I THINK THAT WILL BE SOME WAYS THAT WILL HAVE INSIGHTS THAT WE WON'T HAVE KNOWN ABOUT ANY OTHER WAY. >> ERIC THEY'RE SAYING NORA, YOU HAVE TO MOVE IT. THERE ARE SO MANY QUESTIONS AND I THINK IT'S REALLY SO VERY EXCITING. >> HAPPY TO COME BACK. >> OKAY. AGAIN, SO DON'T MAKE THOSE STATEMENTS BECAUSE I'LL TAKE ADVANTAGE -- >> THAT'S FIEFNLT HAPPY TO FINE. >> THANKS VERY MUCH FOR TAKE THE TIME FOR ACTUALLY THE LEADERSHIP THAT YOU HAVE AND FOR SHARING YOUR VERY POIGNANT STORY, AND I THINK THAT IT SPEAKS TO ITSELF, AND I WAS VERY TAKEN BY THE FACT THAT THE FIRST THING WHEN YOU WAKE UP IS HOW DO WE MAKE THIS AVAILABLE TO OTHERS. THAT GENEROSITY -- >> I WAS AWARE OF ALL THE PRIVILEGE I HAD AND IT WAS ALMOST IMPOSSIBLE EVEN WITH THAT PRIVILEGE, SO WE ARE FAR FROM READY WITH PRECISION MEDICINE FOR ALL BUT HOPEFULLY THIS WILL -- >> ERIC, THANKS A LOT, JOANIE, THANKS VERY MUCH TO YOU ALSO FOR ENSURING THAT ADDICTION IS ON THE FOREFRONT. >> WE APPRECIATE THE HELP THAT YOU'RE GIVING US ON OUR SUBSTANCE USE MODULE. AGAIN, WE WOULDN'T DO THAT ONE WITHOUT YOU. THAT'S COMING PROBABLY MONTHS OUT STILL, BUT THAT'S ONE WE'VE BEEN WORKING WITH YOU ON AND APPRECIATE YOUR SUPPORT OF THAT. THANK YOU. >> ERIC, THANKS ALO. >> ALL RIGHT. SEE YOU. [APPLAUSE] >> IT'S ALSO OUR PLEASURE TO INTRODUCE TO YOU CHRIS AUSTIN, WHO IS THE DIRECTOR OF THE NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCE, NCATS ACTUALLY, AND THIS IS A COMPLETELY NEW CONCEPT OF AN INSTITUTE THE, AN INITIATIVE THAT WAS BROUGHT UP BY FRANCIS AND CHRIS HAS BEEN THE ABLE LEADER OF THAT ORGANIZATION, AND CHRIS HAS ALSO HELPED US IN MANY WAYS, INCLUDING CHAIRING OUR SEARCH COMMITTEE FOR THE DIVISION OF MEDICATION DEVELOPMENT FOR WHICH WE ARE VERY, VERY GRATEFUL FOR THE OUTCOME, SO THANKS A LOT. AND AS I SAID, HE'S THE FIRST AND CURRENT DIRECTOR OF THE NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SIGH SIGH SCIENCES OR NCATS WHOSE MISSION IS TO ENHANCE THE DEVELOPMENT, TESTING AND IMPLEMENTATION OF DIAGNOSTICS AND THERAPEUTICS ACROSS A WIDE RANGE OF HUMAN DISEASES AND CONDITIONS. THE CENTER COLLABORATES WITH OTHER GOVERNMENT AGENCIES, INDUSTRY, ACADEMIA AND THE NON-PROFIT COMMUNITY. BEFORE JOINING NIH OF IN 2002, CHRIS DIRECTED RESEARCH AND DRUG DEVELOPMENT PROGRAMS AT MERCK WITH A FOCUS ON SCHIZOPHRENIA. IN 2016, HE WAS ELECTED CHAIR OF THE INTERNATIONAL RARE DISEASE RESEARCH CONSORTIUM, RDIRC. I EARNED M.D. FROM HARVARD MEDICAL SCHOOL AND COMPLETED TRAINING AT MASSACHUSETTS GENERAL HOSPITAL AND RESEARCH FELLOWSHIP IN GENETICS AT HARVARD. SO CHRIS IT'S A PLEASURE TO HAVE YOU HERE. THANKS VERY MUCH FOR DOING IT. >> THANKS FOR HAVING ME, NORA AND CREW. AS NORA MENTIONED, I'M A NEUROLOGIST BY TRAINING AND I STILL THINK LIKE A NEUROLOGIST, AT LEAST I'D LIKE THINK I DO, SO I SHARE YOUR FASCINATION WITH THE BRAIN AND PARTICULARLY THE DIFFICULTY OF WHAT ARE CALLED FUNCTIONAL DISORDERS. NEUROLOGISTS DIVIDE THEIR WORLD INTO BRAIN DISORDERS WHICH CAUSE STRUCTURAL LESIONS IN THE BRAIN LIKE A STROKE OR ALZHEIMER'S DISEASE, AND ONE IN WHICH THE BRAIN LOOKS RELATIVELY NORMAL, AT LEAST STRUCTURALLY, BUT DOESN'T FUNCTION AS WELL AS WE'D LIKE AND CERTAINLY THE DISEASES THAT YOU ALL STUDY FALL IN THE LATTER CATEGORY. MY OWN INTEREST WAS IN SCHIZOPHRENIA, WHICH SHARES THAT QUALITY. SO WHAT I'M GOING TO TELL YOU ABOUT IS WHAT NCATS' MISSION IS, AND WAYS THAT I WOULD LIKE NIDA AND NCATS TO WORK EVEN MORE CLOSELY TOGETHER THAN IT CURRENTLY DOES, AND THAT'S WHAT NORA ASKED ME TO SPEAK ABOUT, AND WHAT NORA SAID IS RIGHT, NCATS WAS STARTED TO BE A RATHER FUNDAMENTALLY DIFFERENT ORGANIZISM IN THE RESEARCH ECOSYSTEM IN A VARIETY OF WAYS. WE THINK ABOUT WHAT IS COMMON TO DISEASES, NOT WHAT'S DIFFERENT ABOUT THEM, WE THINK ABOUT WHAT'S COMMON TO THE TRANSLATIONAL PROCESS, NO WHAT'S DIFFERENT, AND THERE ARE MANY MORE COMMONALITIES THAN THERE ARE DIFFERENCES. WE'RE FULLY AWARE THAT TRANSLATION IS A TEAM SPORT, AND AS A RESULT, WE DON'T DO EVERYTHING BY OURSELVES. EVERY PROJECT WE DO IS A COLLABORATION WITH SOMEBODY. WE HAVE A GREAT A TRANSLATIONAL EXPERTISE BUT AS A RESULT, WE CAN'T POSSIBLY HAVE EXPERTISE IN ALL 7,000 DISEASES WHICH AFFECT THE HUMAN FAMILY, AND WE RELY ON OUR HUMAN COLLEAGUES FOR THAT, INCLUDING JONATHAN POLLACK AND OTHERS AT NIDA. SO LET ME DIVE RIGHT IN. SO THIS IS THE WORLD WE LIVE IN, IT'S THE WORRELL THAT YOU LIVE IN. WE LIVE IN ALMOST HEARTBREAKINGLY PARADOXICAL TIME WHERE WE KNOW MORE ABOUT OURSELVES AND HEALTH AND DISEASE THAN WE EVER HAVE, PERHAPS EXEMPLIFIED BY THE GENOME PROJECT AND THE WONDERS OF PLEUR OWE POTENT STEM CELLS WHICH YOU SEE ON THE LEFT, AND ONE COULD ADD FUNCTIONAL IMAGING AND ANY NUMBER OF THINGS TO THAT. BUT THE FACT IS, AND YOU KNOW THIS BETTER THAN MOST INSTITUTES, OUR ABILITY TO HAVE A POSITIVE IMPACT ON PATIENTS SUFFERING WITH DISEASE HAS IN NO WAY KEPT UP WITH THAT EPICAL UNDERSTANDING -- WHETHER IT'S IN COMMON DISEASES SUCH AS IN THE UPPER RIGHT, RARE DISEASES IN THE BOTTOM RIGHT, SO THIS CREATES A REALLY UNPRECEDENTED OPPORTUNITY AND NEED TO ASK HOW DO WE DO THIS BETTER AND HOW DO WE APPROACH THIS PROBLEM FOR THE FIRST TIME, INTERESTINGLY, AS A SCIENTIFIC PROBLEM? TO BE STUDIED AS A SCIENTIFIC PROBLEM, MUCH LIKE NEUROSCIENCE OR ENGINEERING OR GENETICS, AND THAT'S NEVER HAPPENED BEFORE, CURIOUSLY. WE COULD TALK ABOUT WHY THAT IS, IT'S AN INTERESTING SORT OF SOCIOLOGICAL HISTORICAL HISTORY, BUT IT IS THE CASE. BUT BECAUSE IT'S ALSO THE CASE WE KNOW SO MUCH MORE ON THE LEFT SIDE, THE OPPORTUNITY TO DELIVER FOR SCIENCE FOR PATIENTS IS GREATER THAN IT'S EVER BEEN, AND IF YOU THINK ABOUT WHAT WE'RE CONFRONTING IN HEAL, IT'S A GREAT EXAMPLE. WHERE WE KNOW AN ENORMOUS AMOUNT ABOUT THE BRAIN, NOT AS MUCH AS WE LIKE, BUT CERTAINLY MORE THAN WE USED TO, AND OUR ABILITY TO INTERVENE IS NOT GREAT AND HOW DO WE FIX THAT AS RAPIDLY AS POSSIBLE. NIDA DOES NOT THE HAVE A LOT OF RARE DISEASES, AND I PROMISED NORA I WOULD WORK WITH HER TO MAKE DRUG ABUSE A RARE DISEASE. MOST OF THESE ARE ACTUALLY RARE DISEASES, BUT IT'S AN INTERESTING NUMBER IF YOU JUST THINK ABOUT WHEN YOU GOT YOU OUT OF TRAINING, BEFORE THE MID EIGHTIES, WHICH IS CERTAINLY WHEN I DID, AND BACK THEN, IT WAS EASY TO STUDY FOR THE BOARDS BECAUSE THE NUMBER OF HUMAN DISEASES, THE MOLECULAR BASIS OF WHICH WAS KNOWN WAS LESS THAN A DOZEN. SICKLE CELL DISEASE, THALASSEMIA, THOSE KINDS OF THINGS, BUT NOW THAT NUMBER IS WELL OVER 6,000 NUMBER OF HUMAN CONDITIONS, THE MOLECULAR BASIS THAT WE UNDERSTAND, IT'S NOT THE SAME THING AS TREATING IT, JUST REMIND YOURSELF OF THE HISTORY OF SICKLE CELL ANEMIA THAT WAS THE FIRST HUMAN DISEASE THAT WAS DISCOVERED IN 1949, AND WE STILL DON'T HAVE A DRUG DIRECTED AGAINST THAT PLEAK MOLECULAR PATHOGENESIS BUT IT CERTAINLY HELPS. THE ISSUE, HOWRVETION FROM PATIENTS POINT OF VIEW IS THAT THIS IS WHERE THEY SEE, WHEN THEY GO TO THE DOCTOR, THEY WANT NOT ONLY A DIAGNOSIS, THEY WANT A TREATMENT, AND ON THAT SIDE, WE'RE NOT DOING TOO WELL. THERE WAS ONLY ABOUT 500 OF THEM THAT HAVE ANY FDA-APPROVED TREATMENT AT ALL AS A NEUROLOGIST, I USED TO SEE PREDOMINANTLY UNTREATABLE DISEASES. THE ONLY THING I COULD TREAT WAS SEIZURES AND PARKINSON'S DISEASE. I LOVED SEEING THOSE PATIENTS BECAUSE THEY WERE THE ONLY ONES I COULD DO SOMETHING FOR, AND I WOULD GO THROUGH ENTIRE DAYS OF HAVING WHOLE SLATES OF PATIENTS FOR WHOM I COULD DO NOTHING. THAT'S ACTUALLY WHAT DROVE ME INTO RESEARCH, THIS PARADOX, AND I'VE BEEN LIVING IN THIS PARADOX EVER SINCE AND TRYING TO DO SOMETHING ABOUT IT, AND THAT'S REALLY WHAT NCATS WAS FORMED TO DO, SO YOU MIGHT SAY, GOSH, WE'RE NOT DOING TOO BAD NECESSARILY BECAUSE WE ALL KNOW IT TAKES 10 TO 15, 20 YEARS TO MAKE AN INTERVENTION OR DRUG, WHATEVER IT IS, TO GET IT APPROVED FOR HUMAN USE, SO MAYBE WE JUST GOT TO WAIT 15 YEARS AND WE'LL SEE A SIMILAR INCREASE IN THERAPEUTICS. UNFORTUNATELY THAT WOULD BE WRONG. I'M GOING TO DEPRESS YOU AT THE BEGINNING THEN I'M GOING TO RESCUE YOU. I'M GOING TO GIVE YOU -- I PROMISE I'M GOING TO RESCUE YOU. BUT WE'VE ALL LIVED THROUGH THIS, THIS IS DURING OUR LIFETIME, THIS IS THE REASON YOU CAN FIT A SUPER COMPUTER THAT I DID MY THESIS ON, I WROTE MY SENIOR THESIS ON IN COLLEGE, INTO ONE OF THESE. INCREASED NUMBER OF TRANSISTORS ON A MICRO PROS ARE SO, IT'S CHANGED OUR LIVES ENORMOUSLY. BUT AT THE SAME TIME, IT'S DONE EXACTLY THE OPPOSITE. THAT IS, THE PRODUCTIVITY HAS BEEN NEGATIVE SINCE THE 1950s, THE NUMBER OF DRUGS ONE GETS PER BILLION DOLLARS SPENT HAS GONE DOWN BY 50% EVERY NINE YEARS SINCE 1950. YOU IMAGINE ANY ORGANIZATION, WHETHER IT'S MAKING DRUGS OR BALL BEARINGS OR SHOES, THAT HAS THIS DRAMATICALLY PRODUCTIVITY GRAPH IS GOING TO GO OUT OF BUSINESS, THEY ARE GOING TO MERGE WITH EACH OTHER AND THE PRODUCTS THEN DO MAKE ARE GOING TO BE EXORBITANTLY EXPENSIVE AND I JUST DESCRIBED THE PHARMACEUTICAL INDUSTRY FOR YOU. WHEN I WAS AT MERCK, THE APPROACH TO THIS PROBLEM WAS WHAT WAS CALLED SHOTS ON GOAL, THAT IS, YOU JUST HAVE TO TAKE MORE SHOTS. WELL, THE PROBLEM WITH SHOTS ON GOAL IS THAT IF YOU HAVE A REASONABLE CHANCE, YOU KNOW WHERE THE GOAL IS AND YOU HAVE SOME IDEA WHAT THE RULES ARE, IT'S NOT A BAD STRATEGY. IF YOU HAVE NO IDEA WHAT THE RULES ARE, YOUR SUCCESS IS IN THE NEGATIVE EX-POANTS, EX-POANTS, DOUBLIN G THE SHOTS ON GLOAL GIVE YOU TWO TIMES NEGATIVE EX-POANTS. WHAT YOU HAVE TO DO IS THINK ABOUT THE PROCESS AS A SYSTEMS ENGINEER WOULD OR BIOSYNTHETIC CHEMIST AND DEVELOP CATALYSTS TO THE LIMITING STEPS. IT'S NEVER BEEN DONE IN TRANSLATION, CURIOUSLY, BUT THAT'S WHAT WE'RE TRYING TO DO. SO ONE OF THE THINGS I LEARNED EARLY ON, AND I ALWAYS TELL TRAINEES THIS, THIS IS WHAT I WAS TOLD I WAS SUPPOSED TO DO. I WAS TRAINED AS A NEUROLOGIST, I'VE GOT TO DIAGNOSE PEOPLE, THAT'S A STROKE UP THERE, IN CASE YOU DON'T RECOGNIZE THAT, AND -- OR I WAS SUPPOSED TO DIAGNOSE GENETIC DISEASE PATIENTS AND PUBLISH A PAPER AND THAT WAS IT. NEUROLOGISTS ARE FAMOUS FOR DOING THIS, AS YOU PROBABLY KNOW. BUT WHAT I DISCOVERED ACTUALLY, WHAT PATIENTS ALL KNOW IS, THAT DOESN'T EQUAL THIS. AS A MOM OF A PATIENT WITH A RARE DISEASE SAID TO ME ONCE A COUPLE YEARS AGO, SHE SAID I LOVE FUNDAMENTAL DISCOVERY, BUT WHEN MY DAUGHTER IS SICK, I CAN'T GIVE HER A PUBLICATION. I THINK ABOUT THAT ALMOST EVERY DAY. BECAUSE WE TEND TO THINK IT DOES. WE CONGRATULATE OUR SERS AND WE SHOULD CONGRATULATE OURSELVES. WHAT'S ON THE LEFT SIDE IS WONDERFUL STUFF, BUT FOR OUR PATIENTS, IT'S NOT. SO HOW DO WE IMPROVE THAT ON A SYSTEMATIC LEVEL? THE THING I FIND THROUGH MY CAREER IS THEY'RE THE SAME ISSUES, WHETHER WE'RE TALKING ABOUT DRUG ABUSE, PSORIASIS, CARDIOVASCULAR DISEASE, THEY'RE ALL THE SAME ISSUES, BUT IT'S NOT ONLY DEVELOPING A DRUG OR DEVICE THAT'S A DISCONTINUITY WITH THE BASIC DISCOVERY, BUT IT'S ALSO GETTING IT TO PATIENTS. AS YOU KNOW BETTER THAN ANYBODY, MODELS OF CARE, DISSEMINATION, IMPLEMENTATION, ARE ABSOLUTELY CRITICAL, SO THAT YOU CAN HAVE WHAT'S IN THE MIDDLE AND IT DOESN'T MATTER TO THE PATIENT, THEIR HEALTH DOESN'T IMPROVE BECAUSE THEY CAN'T GET IT OR THEY CAN'T GET IT EFFECTIVELY. SO THOSE DISCONTINUITY, YOU CAN THINK ABOUT IT AS NCATS' MISSION MISSION. I JUST WANT TO EMPHASIZE THESE WORDS, INNOVATIVE WAYS OF DOING THINGS, AND WE'RE A CATALYST THAT IS WE WORK TOGETHER WITH OTHER ORGANIZATIONS TO HELP THIS WHOLE PROCESS WORK BETTER, BUT AS WE ALL KNOW, I THINK, THE REAL REVOLUTIONS IN SCIENCE HAVE COME FROM NEW WAYS OF DOING THINGS, WHETHER IT'S AN MRI SCAN OR A PCR, SO WE THINK ABOUT THOSE SYSTEMATIC IMPROVEMENTS WHICH WILL GIVE US LOGARITHMIC OR EXPONENTIAL TENFOLD, 20 FOLD, 100 FOLD IMPROVEMENTS IN EFFICIENCY IN THE LIMITING STEPS OF THE TRANSLATIONAL PROCESS. SO WE HAVE THIS REALLY INTERESTING PROBLEM AT NCATS THAT UNHAPPILY YOU DON'T HAVE, THAT EVERYONE IN THE WORLD, I HOPE, KNOWS WHAT DRUG ABUSE IS. NOBODY KNOWS WHAT TRANSLATION IS. SO WE WERE STUCK WITH A CENTER THAT HAS A NAME THAT NOBODY UNDERSTANDS, SO WE ACTUALLY HAD TO DEFINE WHAT OUR NAME IS. WHICH WAS AN INTERESTING EXERCISE. THAT IS, FOR OUR DEAF ANYTHING, IT'S THE PROCESS OF TURNING AN OBSERVATION THAT A SCIENTIST MAKES IN A LAB, A DOC MAKES IN THE CLINIC OR A COMMUNITY HEALTH WORKER MAKES IN A COMMUNITY, THAT OBSERVATION WHERE A LIGHT BULB GOES ON AND SAYS THIS EVENT IN FRONT OF ME THAT NOBODY HAS EVER SEEN, IF I CAN SHOW IT'S ROBUST AND REPRODUCIBLE AND& DEVELOP AN INTERVENTION OF DRUG -- TO REVERSE THAT, I WILL HAVE AN IMPACT ON THE TARGET, THE DISEASE, THE COMMUNITY HEALTH PROBLEM THAT'S IN FRONT OF ME. SO THE WHOLE PROCESS FROM THAT IDEATION, THAT OBSERVATION, TO AN INTERVENTION THAT IS SHOWN TO IMPROVE HUMAN HEALTH IN THE COMMUNITY, THAT'S TRANSLATION. HEALTH DOESN'T HAPPEN IN A CLINICAL TRIAL, IT HAPPENS IN THE COMMUNITY, SO WE HAVE TO KEEP GOING ALL THE WAY TO THE COMMUNITY. SO WHAT'S TRANSLATIONAL SCIENCE? IT FOLLOWS FROM THIS, IT'S THE FIELD OF INVESTIGATION THAT SEEKS TO UNDERSTAND THE GENERAL PRINCIPLES BY WHICH THIS PROCESS HAPPENS. INTERESTINGLY TRANSLATIONAL SCIENCE IS A NEW FIELD, DIDN'T EXIST BEFORE NCATS. SO IT'S A PRETTY EXCITING PLACE TO BE EXCEPT THAT NOBODY UNDERSTANDS IT, AND THAT'S OUR CHALLENGE. IF PEOPLE UNDERSTOOD IT, WE WOULDN'T HAVE THIS PROBLEM. ONE OF THE REASONS QUESTION HAVE THIS PROBLEM IS THAT IF FOLKS LIKE ALL OF US, AND I WAS IN THAT SITUATION FOR MANY, MANY YEARS, I DIDN'T UNDERSTAND WHAT THE DYNAMICS WERE, AND SO THE COMMUNICATION CHALLENGE FOR US IS CONSIDERABLE AND THAT'S WHY I'M GLAD TO TALK TO YOU ABOUT THIS. BUT TRANSLATION IS NOT ONLY A SCIENTIFIC PROBLEM, IT'S ALSO AN ORGANIZATIONAL PROBLEM. SO WHAT ARE THE PROBLEMS THAT WE WORK ON? IF YOU WANT TO THINK ABOUT NCATS HAVING TRANSLATION AS ITS DISEASE, THAT'S OUR DISEASE, WHAT IS THE PROBLEM LIST OF THE TRANSLATIONAL PATIENT? TRANSLATION FAILS 99% OF THE TIME SO IT'S A PRETTY SICK PATIENT, BUT WHAT EXACTLY ARE THE PROBLEMS? THESE ARE THE PROBLEMS, AT LEAST SOME OF THEM, THAT PREVENT FUNDAMENTAL DISCOVERIES FROM GETTING TO PATIENTS, DOESN'T MATTER WHAT THE DISEASE IS, THEY'RE ALL THE SAME PRETTY MUCH, AND FIRST THREE ARE THE REASONS THAT DRUGS FAIL OR INTERVENTIONS FAIL BEFORE THEY GET IN TO PEOPLE, OTHERS GO BETWEEN THE PRE-CLINICAL AND THE CLINICAL WORLD, AND OTHERS ARE MORE CLINICAL OR PUBLIC HEALTH, AND WHEN YOU LOOK AT THIS LIST, YOU REALIZE THERE ARE NO DISEASE NAMES ON IT AND THAT'S ON PURPOSE BECAUSE THEY'RE ALL THE SAME NO MATTER WHAT DISEASE YOU'RE WORKING ON. THEY ALSO FIT INTERESTINGLY INTO WHAT ECONOMISTS CALL THE TRAGEDY OF THE COMMONS. THIS IS AN OBSERVATION THAT PROBLEMS THAT ARE EVERYONE'S PROBLEM IN GENERAL IS NO ONE'S PROBLEM IN PARTICULAR, SO NO ONE TAKES RESPONSIBILITY TO SOLVE IT IT. THIS IS CLASSIC. SO WHOSE PROBLEM -- WAS THIS NIDA'S PROBLEM TO SOLVE? NO. IS IT PFIZER'S? NO. THE CYSTIC FIBROSIS FOUNDATION? NO. THERE'S NEVER BEEN AN ORGANIZATION IN THE WORLD WHOSE JOB WAS TO DO THESE THINGS. WHICH IS KIND OF MIND BOGGLING WHEN YOU THINK ABOUT IT, BUT IT'S THE WAY HUMAN SOCIETIES WORK. INTERESTINGLY. AND IT'S TRUE, CLEAN WATER AND CLEAN AIR ARE CLASSIC EXAMPLES. BUT ON THE CULTURAL SIDE -- THOSE ARE THE SIGN TERRIFIC PROBLEMS. DATA TRANSPARENCY I.P., PROJECT MANAGEMENT, CREDIT FOR TEAM SCIENCE, EDUCATION, TRAINING, COLLABORATIVE STRUCTURES, ALL THESE THINGS, BECAUSE IT'S CLEAR, EVEN IF WE GET THE SCIENCE RIGHT, TRANSLATION STILL FAILS ABOUT HALF THE TIME BECAUSE WE GET THESE THINGS WRONG. SO WE INNOVATE ON THESE PROBLEMS TOO EVERYBODY BIT AS MUCH ON TOXICOLOGY -- SO ON THE PRE-CLINICAL SIDE, WHAT DO WE ACTUALLY DO? WE DIVIDED IT BASICALLY INTO PRE-CLINICAL, CLINICAL AND TECHNOLOGY, SO I'M GOING TO GIVE YOU EXAMPLES OF EACH. IN EACH CASE, THE SCIENCE IS DIFFERENT AND MODEL IS DIFFERENT. AND I'M GOING TO TRY TO MAKE THAT CLEAR, I HOPE. SO ON THE PRE-CLINICAL SIDE, THIS WHOLE PART OF THE ORGANIZATION IS ACTUALLY AN INTRAMURAL PROGRAM, BUT IN THE INTRAMURAL PROGRAM, WE HAVE NO PRINCIPAL INVESTIGATORS, NO TENURE, NO TENURE TRACT, EVERYBODY WORKS ON PROJECT TEAMS, EVERYBODY PROJECT IS A COLLABORATION WITH SOMEBODY, SOMEWHERE IN THE WORLD. SO HOW DOES THIS WORK? HOW IT WORKS IS THAT WE HAVE PROJECT TEAMS OF PEOPLE WHO HAVE LARGELY BEEN IN PHARMA AND BIOTECH, AND I KNOW YOU MET CURT, SO CURT IS A FELLOW TRAVELER HERE, I WAS AT MERCK, HE WAS AT LILI, SO WE SPEAK THIS IDIOSYNCRATIC LANGUAGE THAT WE MAY DELVE INTO, IT'S THE PHARMA EQUIVALENT OF PIG LA 10, LATIN, BUT I LEARNED A LOT IN THAT ENVIRONMENT I NEVER COULD HAVE LEARNED IN ACADEMIA, BUT THE PEOPLE IN ACADEMIA HAVE A DEEP KNOWLEDGE OF DISEASE AND FARGTS THAT IS VERY TARGETS THAT IS VERY HARD TO SUSTAIN IN A PHARMA OR BIOTECH DEPARTMENT, SO THE IDEA IS WE HAVE THESE PROJECT TEAMS, THE TEAMS AT OUR PLACE, THAT COLLABORATE WITH EXTRAMURAL OR INTRAMURAL PEOPLE, PEOPLE OUTSIDE OF NCATS, AND THE PEOPLE WHO WERE STUCK AT VARIOUS STAGES ALONG THE THERAPEUTIC DEVELOPMENT PROCESS EVERYWHERE FROM IDENTIFYING A TARGET TO A PRE-CLINICAL DEVELOPMENT CANDIDATE. DEPENDING ON WHERE THEY'RE STUCK, THEY GO THROUGH YOU A PEER REVIEW PROCESS, AND IF THEY SUCCEED, THEY GET INTO ONE OR ANOTHER OF THESE LITTLE BOXES HERE, AND EACH OF THESE BOXES IS A DIFFERENT PROGRAM, BUT THE MODEL IS THE SAME. JOINT PROJECT TEAM, THEY DON'T GET MONEY, IF WE GIVE THEM MONEY, THEY TONIGHT HAVE DON'T HAVE THE TECHNOLOGY OR EXPERTISE TO DO THIS. TAKE THAT PERSON, PUT THEM ON A JOINT PROJECT TEAM, GIVE THEM A BUDGET, SO IF THEY KEEP GOING, YOU KEEP FUNDING THEM. THAT'S HOW THIS WORKS. AND IDEA IS TO MOVE EACH PROJECT DOWN THE PIPELINE HERE, BUT ALSO DOWN HERE. EVERY PROJECT IS TO TEACH US SOMETHING ABOUT HOW TO DO THE PROCESS BETTER. THAT'S THE TRANSLATIONAL SCIENCE PART OF THIS. THERE ARE DATA OR TOOLS OR REPURPOSED DRUGS OR TECHNOLOGIES OR WHAT HAVE YOU, OFTEN MANY OF THOSE THINGS LEADING TO MORE EFFICIENT EFFECTIVE TRANSLATION. SO LET ME GIVE YOU TWO EXAMPLES OF HOW THIS WORKS. RELEVANT TO THE NIDA MISSION. THIS HAPPENS TO BE A COLLABORATION WITH LAWRENCE BRACKET AT DUKE, WORKING ON RECEPTORS, AND WHAT WAS NECESSARY HERE WAS A VERY SPECIFIC KIND OF PHARMACOLOGY TO MANIPULATE THE GHRELIN RECEPTOR IN A WAY THAT MIGHT BE USEFUL FOR REWARD DISORDERS AND ADDICTION. AND OUR FOLKS, THESE FOLKS HERE, THEY DON'T KNOW ANYTHING ABOUT GHRELIN. THEY PROBABLY DON'T EVEN KNOW HOW TO SPELL IT. BUT THAT'S OKAY BECAUSE LAWRENCE DOESN'T NEED TO KNOW ANYTHING ABOUT ALL THE THINGS THAT THEY DO, HIGH THROUGH PUT SCREENING, CHEMICAL INFORMATICS, ALL THAT STUFF, SO IT'S A JOINT PROJECT TEAM AND THE POINT IS TOGETHER, THEY'VE DEVELOPED A SERIES OF COMPOUNDS THAT ACTUALLY DO WHAT WE'D LIKE THEM TO DO, DEVELOPED AN ASSAY, SCREENED IT ACROSS 40,000 COMPOUNDS IN THAT CASE, DID ABOUT TWO YEARS OF MED CHEM, AND THERE'S CURRENTLY AN ANALOG FROM THE ORIGINAL SKIN THAT'S ACTIVE IN SOME ANIMAL MODELS OF ADDICTION AT A REASONABLE DOSE. THIS IS NOT READY FOR PRIME TIME YET, BUT THE POINT IS THAT THIS TOOK AN IDEA OF AN INVESTIGATOR THAT WOULD HAVE SAT AS AN IDEA OR HE WOULD HAVE TRIED TO DO IT REALLY INEFFICIENTLY AND VIA THIS KIND OF COLLABORATION, THIS HAPPENED VERY RAPIDLY. AND IT BENEFITS EVERYBODY, OF COURSE. LET ME GIVE YOU A SECOND EXAMPLE, THIS IS SOMETHING THAT NORA STARTED, SHE CALLED ME UP A FEW YEARS AGO AND SAID THERE'S THIS REALLY INTERESTING PROJECT WE'D LIKE YOUR HELP WITH IN ANOTHER PROJECT -- ANOTHER PROGRAM FARTHER DOWN THE ROAD, SOMETHING CALLED BRIDGES, WHICH WORKS ON THE -- WELL, LET ME JUST SHOW YOU, WORK WORKS ON THE PRE-IND ENABLING TASK OF CNC REGULATORY SCAPE UL, SCALE UP, THIS IS WITH A COMPANY WORKING ON A TAMPER-RESISTANT OXYCODONE FORMULATION. IT'S REALLY COOL IDEA OF A CLEAVAGE THAT HAS TO GO ON THE STOMACH, PSYCH LIEIZATION -- IT LIB RATES THE OXYCODONE, SO APPARENTLY AS FAR AS I UNDERSTAND, NO MATTER HOW MANY KITCHEN COOKS YOU HAVE, NO ONE HAS BEEN ABLE TO LIBERATE ACTIVE OXYCODONE FROM THE ORIGINAL ORIGINALAGENT. SO WE DID ALL OF THIS WORK DOWN HERE. INTERESTING, I'M SURE SOMETHING YOU'VE TALKED ABOUT, EVEN THOUGH IT GOT FAST TRACK STU STATUS, BECAUSE OF THE BUSINESS MODEL PROBLEM OF THESE KINDS OF COMPOUNDS, IT'S STUCK, I GATHER, OR AT LEAST NOT AS FAST AS WE WOULD LIKE. BUT THE POINT IS THE INITIAL PROBLEM WAS RESOLVED EXTRAORDINARILY QUICKLY BECAUSE OF THE COMBINATION OF NIDA'S EXPERTISE AND OUR EXPERTISE AND THIS COMPANY'S EXPERTISE THAT GOT THEM OVER THIS TRANSLATIONAL ROADBLOCK. WE'RE SPENDING A LOT OF TIME ON NEW WAYS TO IDENTIFY THERAPEUTICS, WHICH ARE STARTING OUT WITH MORE PHYSIOLOGICALLY RELEVANT SCREENING SYSTEMS OR BIOLOGICAL SYSTEMS. THE STATE OF THE ART CURRENT LIE LI IN THE FIELD IS TO DO TESTING DRUGS OR COMPOUNDS IN THIS FORMAT. THIS IS A SAME KIND OF PLATE AS A 96 BUT IT HAS 1,536 WELLS IN IT, VERY, VERY SMALL VOLUMES. FANTASTIC FOR DOING HIGH THROUGHPUT SCREENING BUT VERY HARD TO MAKE A NIZ LOGICALLY RELEVANT CONSTRUCT IN THERE MULTICELLULAR, ET CETERA, AN THEN AT THE OTHER END, THERE ARE TISSUE CHIPS WHICH I'LL TELL YOU ABOUT IN A SECOND IN BETWEEN THINGS LIKE SPHERE OIDS, ORGAN OIDS, PRINTED TISSUES, AND WE'RE DOING ALL OF THESE. AGAIN, ALL OF THESE ARE DONE BY COMBINING THE TECHNOLOGY WE HAVE, WHICH IS IN THE TISSUE PRINTING AND ORGANS ON A CHIP AND DRUG SCREENING AND ALL THOSE TECHNOLOGIES, WITH THE DISEASE EXPERTISE THAT THE INDIVIDUAL I.C. OR INDEPENDENT INVESTIGATOR HAS. SO WE'VE STARTED WITH SKIN, RETINA, AND BLOOD VESSEL, BUT WE'RE MOVING TO THESE, EASY TO PRINT LAMINAR TISSUES, THAT'S WHERE WE STARTED. THE TISSUE CHIP PROGRAM IS SOMETHING YOU MIGHT HAVE HEARD ABOUT. THE IDEA HERE IS THAT INSTEAD OF USING ANIMALS, IF WE CAN USE MUCH LIKE IN THE TISSUE PRINTED SETTING, IF WE CAN HAVE MULTICELLULAR CONSTRUCTS WHICH HAVE THE SAME STRUCTURE AND FUNCTION OF THE UNIT PRODUCTION OF AN INDIVIDUAL HUMAN TISSUE MADE OUT OF HUMAN CELLS, PRIMARY CELLS OR IPS CELLS, AND USE THOSE TO TEST FOR SAFETY AND EFFICACY OF NOVEL THERAPEUTICS, NOT ANIMALS, SO JUST IMAGINE A NEPHRON, A NEPHRON IS A TUBE, SO YOU CAN MAKE A MICRO TUBE THE DIAMETER OF A NEPHRON AND THEN LINE THOSE WITH IPS-DERIVED PROXIMAL TUBULE CELLS AND AMAZINGLY, THEY RECAPITULATE THE PHYSICIAN YOLG THE PHYSIOLOGY AMAZINGLY WELL. WE'VE GOTTEN TO THE POINT NOW WHERE IN CHIP HERE, SORRY FOR THE NAME BUT WE COULDN'T RESIST, SO CHIP IS ON OUR WEBSITE, AND IF YOU CLICK ON ANY OF CHIP'S OREGONS YOU CAN FIND HIS INDIVIDUAL ORGANS, AND WE'VE -- BY WE, I MEAN OUR INVESTIGATORS, FOLKS LIKE LINDA GRIFFITH AND DON AND OTHERS, WHO HAVE DONE THIS, IT'S A TOTALLY EXTRAMURAL PROGRAM, BUT HAVE LINKED THESE TOGETHER INTO A MICRO FLEW I TICK ARE -- ACTIVATE WITH EACH OTHER AND ART VISUAL BLOOD CARRIES THE ANALYTES FROM ONE TO THE OTHER. THIS WAS IN ADDITION TO BEING A REALLY DIFFERENT TECHNOLOGY, WHICH AIMED FOR, AGAIN, LOGARITHMIC IMPROVEMENT IN TIME, EFFICACY AND COST. IT ALSO WAS A NOVEL COLLABORATIVE STRUCTURE. SO THIS NEVER WOULD HAVE WORKED, JUST LIKE THE OTHERS I SHOWED YOU, IT NEVER WOULD HAVE WORKED IF WE TRIED TO DO THIS ON OUR OWN. WE DID IT WITH DARPA AND THE FDA AND A WHOLE SUITE OF EXTRAMURAL INVESTIGATORS, AND THAT'S REALLY WHY THIS WORKED. I JUST WANT TO GIVE YOU ONE EXAMPLE OF WHERE WE ARE NOW. THIS HAPPENS TO BE A PROJECT MOVING ON FROM CREATING NORMAL TISSUES TO DISEASE TISSUES, THIS HAPPENS TO BE PARKINSON'S DISEASE AT CEDARS-SINAI, AND THE IDEA IS CAN ONE USE IPSC DERIVED BE USED WHERE WE HAVE BONE MARROW EPITHELIAL CELLS AND NEURONS, DOPAMINERGIC NEURONS IN THIS CASE TO MODEL THE FUNDAMENTAL PHYSIOLOGY OF PARKINSON'S DEGREES. I DON'T HAVE TIME TO GO THROUGH ALL THE DETAILS BUT I'LL SKIP THROUGH THIS TO TELL YOU HE'S ALREADY CREATED THIS ON A PLATFORM THAT WAS ORIGINALLY CREATED BY A COMPANY -- IT WAS THE -- INSTITUTE, SPUN OUT TO A COMPANY CALLED EMULATE WHICH MODELS THIS SYSTEM, THEN HE'S GOING TO SCREEN ON THIS PLATFORM ALL THE COMPOUNDS THAT EXIST IN THE INTRAMURAL PROGRAM I SHOWED YOU BEFORE, ALL DRUGS APPROVED FOR HUMAN USE WORLDWIDE. THIS GIVES YOU A SENSE, THE TYPICAL PRETTY PICTURES THAT THIS KIND OF RESEARCH ALLOWS YOU TO DO, LOOKING AT THE T.H. CELLS AND THE ENDOTHELIAL CELLS THAT ARE DERIVED FROM THE SAME IPS CELLS, SAME IPS LINE. ONE OF THE THINGS WE'VE BEEN PARTICULARLY EXCITED ABOUT ALTHOUGH IT'S REALLY HARD TO SCALE UP FOR TECHNICAL REASONS IS THE BLOOD-BRAIN BARRIER CHIP. IT'S ONE OF THE FIRST THINGS WE WORKED ON, AND IT WORKS FAIRLY ROBUSTLY BUT IS VERY FIN ICKY, SO TRYING TO GROW THIS UP, TRIKING TO MAKE IT ROBUST AND ENOUGH FOR INDIVIDUAL INVESTIGATORS TO USE, THAT'S WHERE WE ARE NOW. BRAIN CHIPS, THAT'S BEEN INTERESTING TO WORK WITH SOME OF THESE FOLKS. AS YOU MAY KNOW, NOT EVERYONE APPRECIATES THE COMPLEXITY OF THE BRAIN, SO THEY THINK THEY'RE GOING TO CREATE A BRAIN CHIP. YOU THINK, BRAIN CHIP, WHAT PART OF THE BRAIN ARE YOU TALKING ABOUT? YOU MOVE 2 MILLIMETERS, YOU GET TO THE THALAMUS TO A PART OF THE CORTEX, SO WHAT'S BEEN DONE SO FAR, IF YOU SEE THIS IN THE LITERATURE, THEY'RE ESSENTIALLY OVERGROWN NEUROSPHERES WHICH SPONTANEOUSLY LAMINATE, AND IF YOU HALLUCINATE ENOUGH, YOU CAN SORT OF IMAGINE THAT THERE MIGHT BE SOME BRAIN-LIKE ACTIVITY GOING ON AND YOU CAN ACTUALLY MEASURE SPONTANEOUS NEURAL ACTIVITY BUT ONE OF THE IDEAS THAT I'VE WANTED TO DO AND I HAVEN'T MANAGED TO CONVINCE NORA TO DO THIS, THE ONLY IDEA THAT I'VE THOUGHT OF THAT IS SO CRAZY, EVEN NORA WON'T DO IT, WHICH IS REALLY SAYING SOMETHING, BECAUSE SHE'S PRETTY AMBITIOUS, YOU THINK ABOUT HOW WE'VE CREATED THIS THANK YOU THIS CREATED BY ARTIFICIAL BLOOD. IN THE BRAIN, YOU DO HAVE BLOOD DMOACTING THE DIFFERENT PARTS BUT WHAT YOU REALLY HAVE IS ELECTRICAL ACTIVITY, SO COULD YOU CREATE A BRAIN OF DIFFERENT NUCLEI AND PARTS OF THE CORTEX, ALL THE DIFFERENT PARTS OF THE BRAIN YOU CAN IMAGINE, COULD YOU CREATE THAT. IT'S SOMETHING WE'RE VERY INTERESTED IN AND IT'S PERHAPS PHASE 2 OF THE BRAIN PROJECT AND I THINK WE'LL BE READY BY THEN. ON THE CLINICAL SIDE, MANY OF YOU ARE PROBABLY AWARE OF THE CTSA PROGRAM THAT'S ALSO PART OF NCATS. THIS IS A PROGRAM THAT WORKS ON THE CLINICAL SIDE OF THE TRANSLATIONAL DIVIDE WE TALKED ABOUT, 57 OR SO ACADEMIC RESEARCH INSTITUTIONS ALL OVER THE WORLD THAT WOK TOGETHER TO TRY TO SOLVE THESE MAJOR PROBLEMS IN TRANSLATIONAL EFFICIENCY, ALSO THERE'S A LOT OF DOMAIN-SPECIFIC TRAINING. THERE'S MANY, MANY, MANY THINGS THAT THIS PROGRAM DOES, BUT THE ONE THING THAT I WANTED TO JUST MENTION TO YOU, OF ALL THE THINGS THAT THE PROGRAM IS DOING, BECAUSE I THOUGHT IT WOULD BE PARTICULARLY RELEVANT, SOMETHING WE'VE BEEN WORKING ON FOR ALMOST THREE YEARS NOW, THE IDEA BEING IF EACH OF THESE CENTERS IS WONDERFUL IN ITS OWN RIGHT, WHICH IT IS, IF WE TIE THEM ALL TOGETHER, THEY WILL BE AN UNSTOPPABLE FORCE FOR TRANSFORMING CLINICAL TRANSLATION INTO SOMETHING WHICH IS MORE EFFICIENT, MORE EFFECTIVE AND SERVES PATIENTS. AND THAT'S TURNED OUT TO BE THE CASE, SO THIS IS PAFORT PROGRAM PART OF TH E PROGRAM, THE IDEA WAS COULD WE FOCUS ON RECRUITMENT AND ALL THE- LOGISTICAL ISSUES AROUND DOING AN IRB, CONTRACTING, BUDGETING, GOOD CLINICAL PRACTICE, ALL THOSE THINGS, THOSE ARE ADDITIONS TO THE PROGRAM IN ADDITION TO ALL THE HUBS, BUT ALL THE HUBS ARE CONNECTED TO THOSE PIECES OF THE TRIAL INNOVATION NETWORK, AND THEY ALL WORK TOGETHER TO INNOVATE ON THE PROCESS OF DOING CLINICAL TRIALS. AS THIS SAYS, EMPLOYEE NOVEL STUDY DESIGNS, NOVEL STRATEGYIES TO RECRUIT PATIENTS, INTERVENTIONS TO INCREASE RECRUIT AND GET DONE ON TIME AND ON BUDGET WHICH IS UNFORTUNATELY LESS COMMON THAN WE WOULD LIKE, AND SO THIS PROGRAM IS COMPLETELY COLLABORATIVE, AGAIN, IT DOESN'T DO ANY TRIALS WITHOUT AN INVESTIGATOR OR AN IC COMING TO US SAYING WE WANT TO WORK WITH YOU ON THIS, AND IT'S SOMETHING THAT NORA AND I HAVE BEEN WORKING VERY HARD ON AROUND THE HEAL INITIATIVE, TAKING ADVANTAGE OF THIS PROGRAM. SUGGEST MAY HAVE HEARD ABOUT BUT MAY NOT KNOW THAT IT CAME FROM THIS PROGRAM IS THE SINGLE IRB SMART IRB PLATFORM. ONE OF THE FIRST THINGS THAT I TOOK ON WHEN I BECAME DIRECTOR WAS TO TRY TO SOLVE THIS LONG-STANDING PROBLEM OF MULTISITE IRB REVIEW, AND AT LEAST THE FIRST STAGE OF THIS IS DONE, SO THERE'S NOW ABOUT 450 INSTITUTIONS ALL OVER THE COUNTRY WHICH HAS SIGNED ESSENTIALLY THIS TREATY THAT ALLOWS THEM TO RELY ON ANY OF THE OTHERS AND DESIGNATE ANY OF THE OTHERS FOR A TRIAL, SO IT'S A GREAT EXAMPLE OF SOMETHING THAT WHEN IT'S FULLY IMPLEMENTED, THIS SHOULD INCREASE THE EFFICIENCY BY WHICH THIS PROCESS HAPPENS, SO TWO OR THREE YEARS, IT SHOULD BE POSSIBLE IN A MONTH. WE HAVE EXAMPLES OF THAT ALREADY. THAT'S THE KIND OF CHIENG CHAING WE'RE LOOKING FOR. I'M NOT GOING TO READ ALL THIS STUFF OF COURSE, BUT THIS IS WHAT NCATS IS DOING IN THE HEAL INITIATIVE, IT MIGHT -- PROBABLY WON'T SURPRISE YOU NOW THAT WHEN HEAL CAME AROUND, WE THOUGHT, GOSH, WE HAVE ALL OF THESE TECHNOLOGIES, PROJECT TEAMS AND EXPERTISE IN THIS GENERAL PROCESS, WHAT IF WE TOOK THESE BIG GUNS AND WE POINTED THEM AT THE OPIOID PROBLEM AND DID IT IN A COLLABORATIVE MODEL THE WAY WE DO EVERYTHING, AND THAT'S WHAT WE'RE DOING, SO EVERYTHING THAT I TOLD YOU AND A FEW THINGS I DIDN'T TELL YOU ABOUT, INCLUDING STEM CELLS, 3D TISSUES, TISSUE PRINTING, AND ALL THE DRUG DEVELOPMENT WORK COMPLIMENTING WHAT CURT AND HIS TEAM DO, WE'RE WORKING ON THIS IN HEAL. SO I HOPE WE HAVE SOME TIMES FOR QUESTIONS IF YOU WANT TO FOLLOW US, WE HAVE ALL THE USUAL EXPERTISE, CONNECTIONS FOR. SO THANK YOU FOR HAVING ME. [APPLAUSE] >> THANKS VERY MUCH. I ACTUALLY OPEN IT UP FOR ANY QUESTIONS COUNCIL MAY HAVE. >> THANK YOU FOR VERY INSIGHTFUL AND WELL DONE. YOUR ORGANIZATION, NCATS, IS HOW OLD NOW? >> SEVEN YEARS. >> SEVEN YEARS? >> 7 1/2. >> SO IT'S QUITE YOUNG, I GUESS. >> WE LIKE TO THINK WE'RE IN KINDERGARTEN, FIRST GRADE NOW. WE'RE PRECOCIOUS BUT WE VNTD REACHED OUR POTENTIAL YET. >> SO WHAT DO YOU THINK TOOK THE SCIENTIFIC -- WHY DO YOU THINK IT TOOK THE SCIENTIFIC COMMUNITY SO LONG TO REALIZE THE IMPORTANCE OF YOUR MISSION? >> BOY, IS THAT GREAT QUESTION. I WISH I KNEW FOR SURE. IT COMES FROM THE FACT THAT, I THINK, FOR A VARIETY OF REASONS, THIS COMMUNITY HAS HISTORICALLY HAD THE HINDU FABLE BLIND MAN AND THE ELEPHANT PROBLEM. AND ALL THE INCENTIVES, WHETHER THEY'RE ACADEMIC OR PHARMA INCENTIVES, KEECH ONE FOCUSED ON ONE'S PART OF THE ELEPHANT. AND ARE EITHER WILLFULLY OR UNWILLFULLY BLIND TO THE OTHER PARTS. AND IT'S ACTUALLY VERY HARD FOR MOST ACADEMIC INVESTIGATORS OR MOST FOLKS, EVEN A BIOTECH OR A PHARMA, TO APPRECIATE THE OTHER PARTS, AND SO WHAT THEY TEND TO DO, AND WE SEE THIS OVER AND OVER AND OVER AGAIN, BUT THEY WILL DO GREAT WORK IN ONE STAGE OF THE PROCESS, BUT WHAT THE OTHER PERSON NEEDS IS NOT WHAT THEY CREATED. IT'S FINE AS IT IS, YOU CAN PUBLISH IT, IT HELPS THEIR CAREER, BUT IF YOU THINK ABOUT THIS AS A PROCESS WHICH ENDS IN THE PATIENT, WHAT YOU'VE REALLY GOT TO THINK ABOUT IS NOT WHAT YOU NEED BUT WHAT YOUR PARTNER NEEDS. WHAT DOES THE NEXT PHASE IN THE PROCESS NEEDS? IF I'M A BASIC RESEARCHER, WHAT DO MY CLINICAL COLLEAGUES NEED? IF I'M A REGULATORY PERSON, WHAT DO MY PUBLIC HEALTH COLLEAGUES NEED? THEY ALL SPEAK DIFFERENT LANGUAGES, DIFFERENT GOVERNMENT AGENCIES, SO IT'S A REALLY HARD PROBLEM TO ADDRESS. I THINK WHAT'S EVEN WORSE THAN THAT OR COMPOUNDS IT IS THAT THERE'S A LOT OF REALLY MART PEOPLE OUT THERE, AND THEY UNDERSTANDABLY BELIEVE AS WE ALL DO THAT THE WORLD WE SEE IS THE WORLD AS IT EXISTS. WE ALL HAVE THAT "NEW YORKER" CARTOON PROBLEM BUT WE ALL HAVE DIFFERENT POINTS OF VIEW. AND THAT WORKS FINE FOR A LOT OF THINGS, BUT IT DOESN'T WORK IN TRANSLATION. AT ALL. SO CONVINCING PEOPLE THAT, FANTASTIC, WE LOVE WHAT YOU'RE DOING, IT'S AN ENORMOUS VALUE, BUT IT COULD EVEN BETTER IF IT WENT TO THIS STAGE AND THAT'S WHAT IT NEEDS TO GET TO A PATIENT. IT'S BEEN A DIFFICULT THING FOR PEOPLE TO ACCEPT. THE HIGHER UP THEY ARE IN ANY ORGANIZATION, THE HARTDER IT IS THE HARDER IT IS FOR THESM THE TRAINEE, THEY GET IT. DEPARTMENT CHAIRS, VPs IN COMPANIES, OH, BOY. REALLY HARD. >> THANK YOU VERY MUCH. EVERYTHING YOU SAID SOUNDS FAMILIAR TO US IN THE HIV WORLD AND MAYBE ELSEWHERE, WHERE IMPLEMENTATION SCIENCE IS SORT OF THE NEW, NEW THING, AND IT'S PROBABLY THE NEXT STEP ON YOUR BASIC TO CLINICAL TO TRANSLATIONAL AND IMPLEMENTATION SCIENCE AND IT SUFFERS FROM THE SAME PROBLEM AS THE COMMONS, THE DOESN'T BELONG TO ANYBODY, AND THERE'S BEEN AN ARGUMENT ONGOING AROUND WHAT IS NIH'S GOAL AROUND IMPLEMENTATION SCIENCE, WHERE REALLY WHAT YOU'RE TALKING ABOUT IS SCALE UP, SO BASIC TO INTERVENTION, WHICH IS YOUR DOMAIN, BUT IT'S TAKING THOSE INTERVENTIONS AND MAKING SURE PROGRAMS ARE AVAILABLE TO EVERYBODY WHO NEEDS THEM AND THAT THE SYSTEMS EXIST AND FUNCTION EFFICIENTLY TO MAKE THAT HAPPEN. SO I'M JUST CURIOUS ABOUT WHAT YOUR THOUGHTS THE ARE ABOUT IMPLEMENTATION SCIENCE AT THE NIH WHERE THERE IS NO CENTER OR UNIT RESPONSIBLE? >> US A MIGHT IMAGINE, I DIDN'T TALK ABOUT IT AS MUCH BECAUSE THERE'S NO HAD -- PEOPLE LOVE SEEING TISSUE CHIPS SO I LIKE TO SHOW THOSE, BUT THERE'S NO TISSUE CHIP EQUIVALENT FOR IMPLEMENTATION SCIENCE. BUT WE SPEND A LOT OF TIME THINKING ABOUT THIS, AND THE WAY I PUT IT IS TO OUR FOLKS, I CARE, BUT ULTIMATELY I DON'T CARE. IF THEY DO WONDERFUL WORK BUT IT DOESN'T REACH THE PATIENT, THEY HAVE FAILED. AND WE HAVE FAILED. SO THAT PART, THAT LAST MILE OR LAST 10 MILES IS EQUALLY IMPORTANT TO CREATING A COOL NEW TISSUE CHIP. SO PART OF THE PROGRAM IS NOW DIRECTED IN THAT DIRECTION. IT ALWAYS HAD A COMMUNITY ENGAGEMENT PIECE, BUT IT DIDN'T HAVE THIS KIND OF INTERVENTIONAL LET'S CHANGE THE SYSTEM FOCUS THAT YOU REALLY NEED IN IMPLEMENTATION SCIENCE. IT ALSO DIDN'T APPROACH IT OFTEN AS A SIGNS. WE THINK ABOUT THIS, IF YOU'RE TRYING TO IMPLEMENT SOMETHING IN A SYSTEM AND IT DOESN'T WORK, THEN YOU SHOULD HAVE A HYPOTHESIS WHY IT DOESN'T WORK, YOU NEED TO TEST -- AMAZINGLY NOT AS COMMON AS ONE WOULD LIKE. AS FAR AS THE NIH PIECE, IT'S INTERESTING WHEN I FIRST TOOK OVER NCATS, IT WAS RIGHT IN THE MIDDLE OF THE CONGRESSIONAL HOO-HA OVER ECONOMICS, AND SHOULD NIH DO IMPLEMENTATION SCIENCE, AND WE ACTUALLY DIDN'T DO ANY OF THIS WORK FOR THE FIRST COUPLE YEARS. THAT'S NOW DIED DOWN, AND I THINK PROBLEMS LIKE HIV AND HEAL ARE PERFECT REASONS WHY THIS HAS TO BE PART OF WHAT WE DO, I THINK, IF WE ARE GOING TO BE THE NATIONAL INSTITUTES OF HEALTH. LET ME >> LET ME ASK YOU A QUESTION BECAUSE IT JUST RESONATED WHEN YOU SHOWED THAT SLIDE, THE RETURN IS GOING DOWN AND DOWN IN TERMS OF SUCCESS TO BRING PROJECTS OUT THERE. THE WAY WE'RE DOING THINGS IS NOT TENABLE NEITHER BECAUSE IT'S ACTUALLY WHERE EVEN THOUGH WE HAVE MUCH MORE KNOWLEDGE, AND I ALL THINK WE CAN JUST DESCRIBE IT TO INCREASE IN REGULATORY BURDEN, I THINK THERE'S MORE FUNDAMENTAL CHANGES THERE, AND SO I'M CURIOUS TO ACTUALLY -- WHAT YOUR THINKING IS, BECAUSE WE HAVE TO WORK WITH A DIFFERENT -- IT'S NOT JUST THE -- WE HAVE TO GENERATE A NEW WAY FOR US TO INTERACT WITH INDUSTRY, BECAUSE IF WE DON'T DO IT, THEN CREATE NEW MODELS, IT'S GOING TO BE EXTRAORDINARILY SLOW. IT'S ALMOST LIKE WE HAVE TO TRANSFORM THE WAY THAT WE VIEW BOTH THE ACADEMIC WORLD AND THE INDUSTRY DEVELOPMENT WORLD. WHAT ARE YOUR THOUGHTS? >> I COMPLETELY AGREE. WE THINK ABOUT PHARMA AND BIOTECH AS OUR CUSTOMERS, EVERY BIT AS WE THINK ABOUT THE IMPLEMENTATION SCIENCE FOLKS. IF WE DO SOMETHING, IT OUGHT TO RELEVANCE TO THEM, AND SOLVE SOME OF THE PROBLEMS THAT THEY HAVE. ON OUR COUNCIL, SO IF I WAS IN OUR COUNCIL, OUR EQUIVALENT IS ACTUALLY A THIRD BIOTECH VC PHARMA PEOPLE ON OUR COUNCIL, AND A THIRD ARE PATIENTS AND A THIRD ARE ACADEMICS, NON-PROFITS. SO MUCH OF WHAT WITH HE DO IS WITH PHARMAS, WE HAVE WHOLE PROGRAMS MUCH LIKE YOU DO WITH SMALL BUSINESSES AND LARGE BUSINESSES TO DO THESE PROGRAMS COLLABORATIVELY, AND THIS IS ONE OF THE REASONS THAT IT HAS BEEN SOMEWHAT DISPERIOD OF TIMING TO SEE WHAT'S HAPPENING RECENTLY ABOUT NORA VOLKOW WORKING WITH THE PRIVATE SECTOR. I UNDERSTAND THE REASONS, I UNDERSTAND ALL OF THAT, BUT THIS IS GOING TO HURT PATIENTS. IF WE'RE GOING TO GET THESE THINGS TO PATIENTS, WE HAVE GOT TO HAVE A WAY TO DO THESE KINDS OF COLLABORATIONS EFFECTIVELY, AND I THINK THERE ARE WAYS TO DO THEM, BUT YOU'LL NOTICE ON THE LIST OF CULTURAL PROBLEMS THAT I LISTED THERE, NOVEL COLLABORATIVE STRUCTURES WERE PART OF THAT, SO WE ACTUALLY DO PROJECTS, WE'VE DONE THEM IN THE PAST, PROJECT THE SO -- THE COLLABORATIVE STRUCTURE IS REALLY UNUSUAL. AND IF WE CAN MAKE THAT WORK -- BUT THE PROBLEM THAT IT DOESN'T JUST STOP THERE, BUT WE CAN'T FORGET ABOUT WHAT COMES AFT PHARMA, BECAUSE WHAT HAPPENS AFTER THE PHARMA ARE THINGS LIKE COMPARATIVE EFFECTIVENESS, WE SPEND A FAIR A TIME WORKING ON AT HEERNS TOO ADHERENCE TOO. >> WE WORK ON IT BUT I'M ALSO VERY MUCH FOCUSED ON THE NOTION AND THE IMPORTANCE ON HOW AS A CHALLENGE, IT'S VERY EASY TO DEMONIZE INDUSTRY BECAUSE THE COSTS ARE SO VERY HIGH, BUT THE REALITY IS, INDUSTRY IS NOT INVOLVED, WE ARE NOWHERE. AND SO HOW DOES ONE -- AND I THINK WE HAVE TO BE FORCED TO THINK IN WAYS WHERE WE CAN WORK WITH INDUSTRY AND NOT CREATE OBSTACLES, BECAUSE THAT'S MY FEAR. I KNOW THAT THERE'S BEEN CONCERN, BUT AT THE SAME TIME, I LIVE IN THE OTHER WORLD WHERE INDUSTRY HAS NOT BEEN INTERESTED. >> THAT'S WHAT WE STARTED DOING TO TRY TO HELP WITH THIS, IS WE STARTED WRITING CASE REPORTS OF PROJECTS THAT WE DO WHERE THE CASE REPORT IS NOT ABOUT THE DRUG OR DEVICE OR WHATEVER IT IS. IT'S HOW DID WE DO IT. I LIVE IN FEAR OF HAVING SOME PERSON CALL ME UP AND SAY YOU SHOULDN'T HAVE WORKED WITH THAT EVIL PHARMA COMPANY, BUT THOSE OF US WHO KNOW THIS IS TRUE HAVE TO WILLING SAY TO SAY WHAT YOU JUST DID, UNLESS WE WORK WITH PHARMA, WE'RE NOWHERE. THOSE OF US WHO HAVE BEEN IN PHARMA, CURT WILL TELL YOU, IT'S ALL THE SAME PEOPLE. CURT WAS AN ENEMY OF THE PEOPLE, WHAT, A MONTH AGO. AND NOW HE'S A SAINT. BUT THEY'RE ALL THE SAME PEOPLE, THEY WANT TO DO THE RIGHT THING, THEY HAVE PRESSURES JUST LIKE WE DO, THEY'RE NOT GRANT PRESSURES, THEY'RE OTHER PRESSURES, BUT THAT'S WHY THIS DEMONIZATION OF EITHER SIDE IS JUST -- IS JUST DRAMATICALLY COUNTER PRO DUCK TI. BUT I THINK WHAT WE NEED TO HAVE IS MODELS OF SUCCESS. WHAT YOU TEND TO DO IS THE ONLY THING YOU HEAR IS WHEN THEY GO WRONG. ALL THE THINGS THAT GO RIGHT, NOBODY EVER TALKS ABOUT. SO THAT'S WHAT WE'RE TRYING TO DO. >> CHRIS, AND I REALLY APPRECIATE IT AND I'M SORRY TO PUT YOU ON THE SPOT BECAUSE I WANTED YOU TO GO WITH ME INTO THE RECORD. I DO THINK IT IS -- >> OH, BOY, WE THINK ABOUT IT ALL THE TIME. >> IT'S EXTREMELY IMPORTANT. AND I ACTUALLY -- CHRIS, THANKS VERY MUCH. I THINK THERE ARE MANY -- I MEAN, YOU SPOKE OF TWO EXTREMELY IMPORTANT PROJECTS, SO I WOULD SORT OF -- THE WAY THAT I DEAL WITH THE HEEL IS DHRB WILL GIVE US THE OPPORTUNITY, HOW WE CAN MAKE OUR ACTIVITIES MUCH MORE EFFICIENT, HOW WE CAN INTEGRATE. BUT THANKS VERY MUCH FOR COMING AND FOR SUPPORT OF THE MISSION. >> THANK YOU. SEE YOU. THANK YOU. [APPLAUSE] WE ARE LATE BUT WE ARE GOING TO GIVE YOU A 10 MINUTE BIOLOGICAL BREAK. IT IS 3:00. BE BACK AT 10 PAST 3:00 PLEASE. THANKS A LOT. DR. REDONNA CHANDLER, HEALING INITIATIVE, WHICH SHE IS DOING WITH SAMHSA, AND REDONNA BASICALLY HAD BEEN AT NIDA, THEN LEFT NIDA FOR NCATS AND THEN CAME BACK AS THE DIRECTOR OF THE AIDS RESEARCH PROGRAM. SHE BRINGS EXTENSIVE SCIENTIFIC AND ORGANIZATIONAL LEADERSHIP AND RECENTLY SERVED AS THE DEPUTY DIRECTOR FOR THE DIVISION OF CLINICAL INNOVATION AT THE NCATS THAT YOU JUST HEARD ABOUT THAT CHRIS WAS GIVING A PRESENTATION ON. HER RESEARCH EXPERTISE SPANS MULTIPLE AREAS, INCLUDING RESEARCH WITHIN THE INDIVIDUALS INVOLVED WITH THE CRIMINAL JUSTICE SYSTEM, AND SHE HELPED DEVELOP THAT PROGRAM AT NIDA. CLINICAL TRIALS. IMPROVING ADHERENCE TO DRUG ABUSE TREATMENT AND HIV CARE, AND IMPLEMENTING EVIDENCE-BASED TREATMENTS INTO ROUTINE PRACTICE SETTINGS. IT IS THIS DEPTH OF EXPERIENCE AND EXPERTISE WHICH PROVIDE HER WITH THE NEEDED BACKGROUND TO THE HEALING COMMUNITY PROGRAM SO SHE'LL GIVE US A MORE DETAILED DESCRIPTION OF THE PROJECT AND WHERE WE ARE AND WHAT WE AIM TO ACHIEVE. REDONNA, THANK YOU. >> THANK YOU, NORA. THEE ALL FOR ALLOWING ME TO PRESENT. I'M GOING TO TALK ABOUT THE HEALING COMMUNITY STUDY ON BEHALF OF NIDA AND NIH AND ALSO I'M REPRESENTING MY OF SELF AND MY SCIENTIFIC COLLABORATOR, DR. CHRIS JONES WHO IS AT SAMHSA. THE HEALING COMMUNITY STUDY IS BEING DONE IN PARTNERSHIP WITH SAMHSA. IT IS A PART OF THE NIH HEAL INITIATIVE, WHICH IS HAPPYING IS HELPING E ND ADDICTION LONG TERM AND IT'S A PARTNERSHIP WITH NIH, NIDA AND SAMHSA. SO I'M GOING TO GIVE YOU A LITTLE MORE INFORMATION. WE'RE ALL AWARE OF THE PROBLEM OPIOID RELATED OVERDOSE FATALITIES CONTINUE TO RISE AND THAT THERE IS A RECOGNIZED GAP BETWEEN THOSE WHO COULD BENEFIT FROM SOME TYPE OF AN INTERVENTION AND THOSE WHO ACTUALLY RECEIVE INTERVENTIONS. IN SPITE OF THE FACT WE HAVE AN ARM MEN TEAR YUM OF EVIDENCE-BASED PREVENTION TREATMENT AND RECOVERY SUPPORT INTERVENTIONS THAT HAVE BEEN DEVELOPED OVER THE DECADES AT NIDA AND OTHER PLACES THAT SUPPORT RESEARCH, WE KNOW THERE IS VERY LITTLE PENETRATION OF THOSE INTERVENTIONS BEYOND CLINICAL RESEARCH SETTINGS INTO COMMUNITIES, SO WE FEEL THERE IS A NEED FOR STRATEGIES THAT WILL HELP COMMUNITIES TO BE ABLE TO UNDERSTAND THEIR UNIQUE NEED WITH REGARD TO THEIR OPIOID CRIES AND TO DEVELOP A RESPONSE STRATEGY THAT WILL INTEGRATE INTERPREVENTIONS ACROSS MULTIPLE SETTINGS THAT COULD OR ARE CURRENTLY DELIVERING CARE. CURRENTLY THERE ARE FOUR MAIN GOALS FOR THE HEALING COMMUNITY STUDY. ONE IS TO DEVELOP THOSE STRATEGIES THAT WILL HELP COMMUNITIES TO RESPOND RAPIDLY AND EFFECTIVELY TO THEIR OPIOID CRISIS AND TO FOCUS SPECIFICALLY ON OPIOID OVERDOSE FATALITIES AND IMPROVE OUTCOMES, TO MEASURE THE IMPACT THAT INTEGRATING EVIDENCE-BASED PREVENTION AND TREATMENT CONTINUUM FOR OPIOID MISUSE, OUD, OVERDOSE AND OVERDOSE FATALITIES ACROSS MULTIPLE SETTINGS, INCLUDING HEALTHCARE, BEHAVIORAL HEALTH AND JUSTICE BUT WE ALSO WRECK REC. NIEZ THERE ARE OTHER SETTINGS INCLUDING FIRE DEPARTMENTS, POLICE DEPARTMENTS, FAITH-BASED ORGANIZATIONS, ET CETERA, AND WE WANT TO REALLY BE ABLE TO DETERMINE THOSE FACTORS THAT CONTRIBUTE BOTH TO SUCCESSFUL IMPLEMENTATION AND SUSTAINABILITY, WHETHER THERE ARE STRUCTURAL FACTORS, ORGANIZATIONAL FACTORS, POLICY, BUT PARTICULARLY FINANCING AND PAYMENT STRUCTURES, AND FINALLY TO DETERMINE THE INCREMENTAL COST AND THE COST-EFFECTIVENESS OF THE COORDINATED INTEGRATED EVIDENCE-BASED PREVENTION AND TREATMENT SYSTEM COMPARED TO THE STANDARD OF CARE OR WHAT CURRENTLY EXISTS WITHIN COMMUNITIES. SO WE HAVE A SINGLE PRIMARY OUT COME AND THAT'S A LITTLE UNUSUAL FOR AN NIH FUNDED STUDY IN THAT IT HAS A VERY AMBITIOUS GOAL ATTACHED TO IT, WHICH IS NOT JUST TO SIGNIFICANTLY REDUCE OPIOID-RELATED OVERDOSE FATALITIES BUT TO DO IT BY 40% IN THREE YEARS. WE HAVE NUMEROUS SECONDARY OUTCOMES THAT WE'VE BEGUN TO THINK ABOUT, BUT THERE WILL LIKELY BE OTHER SECONDARY OUTCOMES THAT WILL BE IMPORTANT THAT WILL BE PART OF APPLICATIONS. THE CRITERIA FOR A SECONDARY OUTCOME IS THAT WE WANT THEM TO BE A PART OF THE LOGIC MAP THAT WOULD HELP US WITH THE OVERALL GOAL OF REDUCING OVERDOSE FATALITIES, THINGS LIKE INCREASING THE NUMBER OF PEOPLE THAT ARE RECEIVING TREATMENT FOR OPIOID USE DISORDER, SUSTAINING THEM IN CARE FOR BEYOND SIX MONTHS, INCREASING THE NUMBER OF INDIVIDUALS THAT WILL BE RECEIVING RECOVERY SUPPORT SERVICES, AND ON THE FRONT END, TRYING TO INCREASE THE NUMBER OF INDIVIDUAL WHO ARE RECEIVING SOME TYPE OF EVIDENCE BASED PREVENTION INTERVENTION TO PREVENT MISUSE AND FURTHER MOVEMENT INTO ADDICTION. WE HAVE SOME STRUCTURAL CHANGES WITHIN COMMUNITIES THAT WE THINK ARE GOING TO BE IMPORTANT IN BEING ABLE TO REDUCE OPIOID OVERDOSE FATALITIES INCLUDING THINGS LIKE REDUCING THE NUMBER OF OPIOIDS THAT ARE AVAILABLE WITHIN THE COMMUNITY BY CHANGING PRESCRIBING PATTERNS, EBBS PANING EXPANDING SERVICES IN MULTIPLE SETTINGS SIMULTANEOUSLY, INCREASING THE NUMBER OF SPECIALIZED TREATMENT PROGRAMS THAT ARE OFFERING MEDICATION TO ADDRESS OPIOID USE DISORDER, THE NUMBER OF PROVIDERS THAT PRESCRIBE AND MONITOR THE USE OF MEDICATION, AVAILABILITY OF NALOXONE, ENSURING THAT HEALTHCARE SETTINGS ARE ACTUALLY SCREENING FOR OPIOID MISUSE, AND TRYING TO DETERMINE WHAT A BRIEF INTERVENTION MIGHT LOOK LIKE FOR PEOPLE WHO DON'T HAVE OPIOID USE DISORDER BUT YOU HAVE SOME PROBLEMATIC USE THAT'S BEGINNING, INCREASING PARTNERSHIPS BETWEEN SETTINGS WHERE YOU SEE PEOPLE THAT ARE AT VERY HIGH RISK OF AN OIP OIP YOID RELATED OVERDOSE LIKE THE JUSTICE SYSTEM TO DELIVER INTEGRATED CARE AND OTHER SYSTEMS BASED ON NEED BY THE COMMUNITIES AND THE INVESTIGATOR TEAMS. WE INTEND TO FUND UP TO THREE RESEARCH SITES, AND THESE ARE SOME OF THE REQUIREMENTS THAT WERE A PART OF THE NOTICE OF INTENT TO PUBLISH. THE RESEARCH MUCH TAKE PLACE IN HIGHLY AFFECTED COMMUNITIES, COULD BE DEFINED AS COUNTIES, CITIES OR TOWNS. ALL THE COMMUNITIES MUST BE WITHIN A SINGLE STATE THAT IS BURDENED WITH HIGHER THAN AVERAGE RATES OF OVERDOSE MORTALITY AND OPIOID-RELATED MORBIDITY AND OTHER COMPLICATIONS, AND 30% OF THE COMMUNITIES MUST BE CONSIDERED RURAL, AND DEAF NIGMSS WILL BE PROVIDED IN THE FUNDING OPPORTUNITY ANNOUNCEMENTS. THEY MUST LEVERAGE FEDERAL, STATE, LOCAL FOUNDATION AND OTHER RESOURCES AND INFRASTRUCTURE FOR TWO REALLY IMPORTANT PIECES OF THE STUDY. FIRST IS TO COLLECT DATA, BECAUSE HELPING A COMMUNITY UNDERSTAND THEIR LOCAL EPIDEMIC MEANS THEY HAVE TO BE ABLE TO COLLECT DATA TO DO SO, AND THEN TO DEVELOP A RESPONSE STRATEGY AND DELIVER PREVENTION AND TREATMENT SERVICES. ONE OF THE RESEARCH SITE KEY PERSONNEL IS GOING TO BE REQUIRED TO BE A GOVERNMENT OFFICIAL. AND THAT PARTICULAR INDIVIDUAL SHOULD BE ABLE TO INFLUENCE THE WAY THAT SUBSTANCE ABUSE PREVENTION AND TREATMENT WILL BE DELIVERED ACROSS MULTIPLE COMMUNITIES THAT ARE GOING TO BE A PART OF THE RESEARCH SITE. EACH RESEARCH SITE WILL HAVE TO INCLUDE HEALTHCARE, BEHAVIORAL HEALTH AND JUSTICE SETTINGS. WE ARE CONCEPTUALIZING THIS AS APPLYING CLUSTER RATHER TAN INDIVIDUAL TRIAL DESIGNS. WE'RE NOT TRYING TO DEVELOP AND TEST NEW INTERVENTIONS, WE'RE TRYING TO FIGURE OUT HOW TO TAKE THOSE INTERVENTIONS TO SCAIM AND HOW TO TEACH COMMUNITIES HOW TO DO THAT, AND THEY WILL BE IMPLEMENTING COMMON DATA ELEMENTS, MEASURES AND APPROACHES. WE'LL FUND ONE DATA COORDINATING CENTER. THE DATA COORDINATING CENTER WILL SUPPORT COMMUNICATION AND COLLABORATION, THEY WILL ALSO HAVE A HUGE DATA ASPECT, WHICH WILL INCLUDE MANAGEMENT OF DATA, THE WAY IN WHICH DATA GETS COLLECTED FOR THE CROSS SITE RESEARCH QUESTIONS, THEY'LL BE RESPONSIBLE FOR LEADING THE ANALYSES FOR THE CROSS-SITE RESEARCH QUESTIONS AND MODELING, AND THEN THEY WILL BE RESPONSIBLE FOR LEADING THE HEALTH ECONOMICS RESEARCH AND CONDUCTING THE HEALTH ECONOMICS RESEARCH. AND IMPORTANT FOR THE DATA MANAGEMENT PIECE IS THAT THE RESEARCH SITES THAT ARE GOING TO BE COLLABORATING WITH COMMUNITIES WILL HAVE A LOT OF DATA. THEY'LL BE DOING A LOT OF THEIR OWN ANALYSES, BUT THERE ARE SOME THINGS FOR WHICH THERE WILL BE SOME OVERARCHING ANALYSES DONE BY THE DATA COORDINATING CENTER. WE ALSO WANT TO MAKE SURE THAT WE ARE EXECUTING THIS STUDY QUICKLY, EFFECTIVELY, SO THE DATA COORDINATING CENTER WILL WORK WITH THE RESEARCH SITES IN ORDER TO DEVELOP A PROCESS FOR COLLECTING METRICS FOR DEVELOPING METRICS AND COLLECTING METRICS TO MONITOR THE STUDY IMPLEMENTATION AND PROGRESS AND ALSO FOR COLLECTING AND REPORTING ON ENSURING THAT THOSE COMMUNITY STRUCTURAL CHANGES THAT ARE A PART OF THE LOGIC MODEL ARE ACTUALLY HAPPEN HAPPENING, THAT WE EXPECT WOULD BE ASSOCIATED WITH DECREASING OPIOID-RELATED OVERDOSE FATALITIES. HERE'S A FEW OF THE ACTIVITIES THAT HAVE BEEN UNDER WAY TO DATE ON JUNE 18TH, WE HAD PLANNING MEETING WHERE WE INVITED KEY STAKEHOLDERS, INVESTIGATORS AS WELL AS PEOPLE FROM DIFFERENT CONSTITUENCY GROUPS AND OTHER FEDERAL COLLABORATORS. THAT MEETING WAS RECORDED, AND YOU CAN GO TO THE NIDA WEBSITE AT THE URL LISTED HERE IN ORDER TO LISTEN TO THOSE PROCEEDINGS. WE PUT OUT A REQUEST FOR INFORMATION IN JUNE THAT CLOSED IN JULY, AND THE SUMMARY OF THAT MEETING IS GOING THROUGH THE FINAL APPROVAL -- I'M SORRY -- THE SUMMARY OF THAT INFORMATION FROM THE REQUEST IS GOING THROUGH FINAL APPROVAL AT THE NIDA O.D.'S OFFICE AND WILL BE AVAILABLE ON THE NIH HEAL WEBSITE AS WELL AS THE NIDA WEBSITE. WE HOPE WITHIN THE NEXT -- WE HOPE SOON. WE ISSUED TWO NOTICES OF INTENT TO PUBLISH THAT PROVIDED MUCH OF THE INFORMATION I'VE PRESENTED SO FAR, ALTHOUGH I'VE GIVEN YOU A LITTLE BIT OF ADDITIONAL INFORMATION IN JULY, AND NORA ALREADY TALKED ABOUT OUR ANTICIPATED DATE FOR PUBLISHING THE FUNDING OPPORTUNITY ANNOUNCEMENT, ANTIPATED DATE IS DECEMBER 17TH, SO WE CERTAINLY HOPE THE FOIAs WOULD COME OUT IN SEPTEMBER. REVIEW WILL COME OUT THIS WINTER AND MY HOPE IS WE'LL BE ABLE TO STAND THIS UP AND HAVE OUR FIRST THREE-DAY KICKOFF PLANNING MEETING THE END OF FEBRUARY TO THE BEGINNING OF MARCH. NOW DO WE HAVE TIME FOR QUESTIONS AND COMMENTS? OKAY. >> THANKS, RED DONNA, THAT WAS VERY GOOD. I WAS INTRIGUED BY THE GOAL OF 40%, AND I KNOW THAT WAS PROBABLY IN THE AUTHORIZING LEGISLATION FOR THE BILL SO YOU HAVE THREE YEARS OR IS THAT -- LET ME GO THROUGH THAT AND BACK IN THE TAI YOU HAD TO SET GOALS FOR THE COUNTRY IN HOW YOU WERE GOING TO REDUCE DRUG USE, I GOT A WHOLE INTERAGENCY TOGETHER AND THEY SAID MAYBE OVERALL USE 10%. THAT PERSON SLAMMED HIS TABLE ON THE TABLE AND SAID GREAT, IT'S GOING TO BE 50% IN FIVE YEARS, AND IN FIVE YEARS, BY THE WAY, I WON'T BE HERE. BUT THAT GOAL INTRIGUED ME BECAUSE OF ALSO THE REQUIREMENT AROUND I THINK YOU SAID THREE RESEARCH SITES THAT WILL BE GEOGRAPHICALLY SELECTED, CITY, TOWNS OR COUNTIES, I THINK IT WAS, WITH THE HIGHEST RATES OF OVERDOSE MORTALITY. I'M SEEING ABOUT THE MATH ON THAT GOING, SOME OF THE AREAS HAVE THE HIGHEST RATES OF OVERDOSE, DEATHS, MAY NOT BE THE MOST POPULATED AREAS OF THE COUNTRY, SO YOU'VE GOT A MATH PROBLEM. MAY END UP SELECTING AREAS FOR RESEARCH SITES THAT SIMPLY WON'T DRIVE YOU TO THE 40% GOAL. IF YOU MOVE TOWARDS THE GOAL, IN TODAY'S WORLD, THAT'S GOOD ENOUGH, BUT I'M JUST CURIOUS ABOUT, I GUESS IN THE END SORT OF THIS MATH PROBLEM, I DON'T THINK ANYBODY CAN ANSWER THAT, BUT I'M MORE CURIOUS ABOUT HOW YOU INTEND TO SELECT THE RESEARCH SITES THEMSELVES. ACROSS STATES AND THINGS LIKE THAT. SO YOU CAN THINK ABOUT GETTING TO THOSE NUMBERS. >> SO LET ME BREAK THIS DOWN A LITTLE BIT AND PROVIDE THE INFORMATION THAT AT THIS POINT I'M ALLOWED TO PROVIDE BECAUSE SOME OF THE QUESTIONS YOU'RE ASKING ASKING ABOUT HOW WE'RE GOING TO SELECT SITES, I CAN'T SPEAK TO BECAUSE WE HAVE FUNDING OPPORTUNITY THE ANNOUNCEMENTS THAT HAVEN'T EVEN BEEN RELEASED YET. WHAT I CAN SAY IS THAT IT IS 40% ACROSS ALL OF THE COMMUNITIES THAT ARE PARTICIPATING IN THE STUDY COMPARED TO BASELINE. SO IT'S THE NOT INTENDED TO DECREASE OPIOID-RELATED OVERDOSE -- THE STUDY IS AMBITIOUS BUT IT'S NOT SO AMBITIOUS AS TO THINK THAT IT IS GOING TO BE THE END ALL AND BE ALL TO THE ENTIRE OPIOID CRISIS ACROSS THE COUNTRY. THE SECOND THING IS WE ARE GOING TO FUND UP TO THREE RESEARCH SITES. THOSE RESEARCH SITES WILL BE PARTNERING WITH MULTIPLE COUNTY, TOWNS, CITIES, WHICH THEY WILL DEFINE AS COMMUNITIES. AS THEY COME IN FOR AN APPLICATION. THEY WILL PARTNER WITH THOSE IN SAYING EL STATE. THERE WILL BE MORE INFORMATION ABOUT THOSE ISSUES IN THE FOIA. I'M LOOKING AT SUSAN AND SHE'S SAYING I SHOULDN'T SAY A LOT MORE THAN THAT UNTIL THE FUNDING ANNOUNCEMENTS OFFICIALLY COME OUT. SO WE'VE WORKED REALLY HARD TO MAKE SURE THAT WE PROVIDED A LOT OF CLARIFICATION. IF YOU'RE ASKING ABOUT THE 40% NUMBER AND YOU'RE TRYING TO DO IT IN A VERY TACTFUL WAY, I GUESS WHAT I WOULD SAY ABOUT THE 40% COMPARED TO BASELINE IS THAT WE WANTED TO MAKE SURE THAT THIS WAS SOMETHING THAT WAS GOING TO ACTUALLY HAVE A MEANINGFUL IMPACT ON THE LIVES OF AMERICANS, AND IN THE LIVES OF THESE PARTICULAR COMMUNITIES. IT IS A SIGN IT TISK QUESTION ABOUT WHETHER OR NOT WE CAN ACHIEVE IT, BUT IF WE DON'T SET THAT TYPE OF GOAL, WE DON'T STRIVE IT AND DON'T DESIGN THE SCIENTIFIC STUDY IN A WAY TO GET THERE, THERE'S ONE THING FOR SURE, WE WON'T GET THERE. IF WE SET THE GOAL SMALLER THAN THAT, THAT'S WHAT WE WOULD WORK FOR, BUT IF WE SET SOMETHING THAT IS TRULY THAT ASPIRATIONAL, THAT BIG AND AMBITIOUS, AND WE DRIVE EVERYTHING TOWARD THAT, THEN WE CAN ONLY HOPE THAT WE CAN BE EVEN MORE SUCCESSFUL AND A LOT OF THINGS FOR A LOT OF PEOPLE WILL IMPROVE. DRIEFING THIS LEVELDRIVING THIS LEVEL WILL ALSO HELP PEOPLE STRUGGLING WITH ALCOHOL, PEOPLE THAT ARE STRUGGLING WITH COCAINE, STRUGGLING WITH METHAMPHETAMINES, SO IN THAT SENSE, IT IS A MULTI-SUBSTANCE USE BECAUSE THE WAY IN WHICH THE STUDY IS CONCEPTUALIZED, ALL BOATS WILL RISE TOGETHER AND CAN AND WILL I THINK THINK RISE TOGETHER. >> SO THE 40% IS AN ASPIRATIONAL GOAL BUT THE APPLICANTS WHO COME IN HAVE TO HAVE A PLAN TO GET TO THAT GOAL, SO THE BURDEN IS ON THEM TO FIGURE THAT OUT AS PART OF THE PROCESS. THAT'S A WHOLE DIFFERENT -- THAT MAKES A LOT ARE MO SENSE. >> I THINK THE BURDEN WILL BE ON ALL OF US TO COME TOGETHER AFTER THE APPLICATION TO APPLICATIONS HAVE COME IN, REVIEWERS WILL CERTAINLY BE LOOKING AT THE FEASIBILITY THAT THE APPLICANTS HAVE PUT TOGETHER FOR ACHIEVING THAT PARTICULAR GOAL, WE'LL BE LOOKING AT THAT, THEN IT'S A UM1 MECHANISM THAT'S PUBLICLY AVAILABLE, IT'S A COOPERATIVE AGREEMENT, SO CHRIS AND I WILL BE INVOLVED IN HELPING SHAPE AND DEVELOP THE SCIENCE, BUT HAVING THAT GOAL ALSO TIGHTENS WHAT WE NEED TO DO IN THAT EVERYTHING NEEDS TO MAP LOGICALLY ON TO BEING ABLE TO ACHIEVE THAT GOAL AS WELL. SO I THINK IT WILL KEEP US VERY FOCUSED. >> SOME OF THE SPACES WE'RE GOING TO BE GOING, WE WANT TO DO EVIDENCE-BASED INTERVENTION BUT THE LEVEL OF EVIDENCE VARIES FROM ONE TO THE OTHER BUT ON THE OTHER HAND, WE DON'T HAVE TIME ON OUR SIDE, SO THERE IS AN URGENCY, SO IN THAT RESPECT IT'S NOT YOUR CLASSICAL TYPICAL ACADEMIC STORY. IT'S GOING TO REQUIRE FOR US TO BE VERY CREATIVE, AND TO GENERATE A SYSTEM WHERE WE CAN RAPIDLY LEARN AND MODIFY IT, SO IN THAT RESPECT, IT WILL BE DIFFERENT, AND I'M BASICALLY MAKING IT VERY CLEAR IN TERMS OF THE DECISION PROCESS, YES, WE WANT TO BE ABLE TO PICK UP STATES THAT ARE AFFECTED IMPORTANTLY BY THE EPIDEMIC, BUT WE ALSO HAVE TO BE ABLE TO PICK UP PLACES WHERE THERE IS AN INFRASTRUCTURE THAT WILL ENABLE YOU TO DO IT, BECAUSE OTHERWISE IT'S JUST A THEORETICAL EXERCISE. AND THAT'S WHERE THE REVIEWERS ARE GOING TO HAVE TO BE ABLE TO EVALUATE THE LIKELIHOOD THAT THOSE SITES WILL BE ABLE TO DELIVER AND WHY ALSO WE ARE HIGHLIGHTING THE IMPORTANCE OF THAT PERSON THAT WORKS IN THE STATE THAT HATS CAPABILITY TO PUT THEIR RESOURCES FOR TREATMENT AND PREVENTION. AND THE OTHER ISSUE THAT CAME ALONG AND WAS DISCUSSED BACK AND FORTH BECAUSE OF THE GEOGRAPHICAL HETEROGENEITY ACROSS THE COUNTRY AND HOW IT'S BASICALLY CHANGING, SO A COMMUNITY WHERE FENTANYL CAME IN VERY EARLY ON, SO THAT RISES VERY RAPIDLY, BUT ONE WHERE FENTANYL HASN'T GOT THERE WILL START TO SEE AN INCREASE. SO WE ARE CONSIDERING THAT THERE ARE CERTAIN VARIABLES THAT ARE GOING TO BE OUTSIDE OF OUR CONTROL WHICH RELATE, FOR EXAMPLE, THE INPUT OF DRUGS, AND THE P.I.s ARE GOING TO BE TASKED TO ACTUALLY IDENTIFY THEIR RESOURCES, HOW ARE THEY GOING TO ACHIEVE, BUT ALSO WHAT MAY BE THE RISKS THAT -- WHAT RIXES THEY IDENTIFY THAT COULD INTERFERE WITH THEIR CAPACITY TO SUCCEED. I THINK THE OTHER ASPECT THAT IS VERY GOOD, AND REDONNA BRINGS TO LIEPT IS FIRST OF ALL HER ABILITY BY HAVING PLAYED SUCH AN IMPORTANT ROLE WITH A JUSTICE SETTING AND ALSO AT THE CITY, AT NCATS WITH THE CTSA, TO TAKE ADVANTAGE OF THE INFRASTRUCTURE THAT EXISTS ALREADY IN THOSE STATES. CARLOS? >> RELATED TO THAT, OUR PRIOR INITIATIVES, YOU KNOW, RETAIN THE OTHER INITIATIVE -- STTR, ET CETERA, THAT YOU'VE DONE, AND MY GOING TO BE BUILDING ON OTHER THINGS THAT WERE DONE PREVIOUSLY, AND HOW WOULD YOU SEE THAT INCORPORATING? >> IN MY MIND, THE MODEL THAT WE ESTABLISH FOR STTR IS SOMETHING THAT DEFINITELY IS KIND OF BUILT IN TO THIS, IN THAT WE FOUND A WAY -- ST IT R WAS A LITTLE DIFFERENT BECAUSE WE HAD DIFFERENT FUNDING OPPORTUNITY ANNOUNCEMENTS THAT BROUGHT TOGETHER INVESTIGATORS THAT HAD INDEPENDENT R01s AND WE FOUND SOME DIFFERENT WAYS TO HARMONIZE AND DLAB RATE AROUND DATA. THIS IS GOING TO BE A LITTLE DIFFERENT IN THAT AT LEAST IN THE BEGINNING, WE'RING GO TO HAVE TWO FUNDING OPPORTUNITY ANNOUNCEMENTS, WE'RE GOING TO FUND THREE RESEARCH CENTERS THAT ARE GOING TO BE A PART OF A COOPERATIVE AGREEMENT, BUT THERE WILL BE SOME DATA CAPTURE THAT WILL BE UNIQUE TO EACH OF THE RESEARCH CENTERS AND TO THE COMMUNITIES AND THERE WILL BE SOME OVERALL HARMONIZATION, SO I DEFINITELY AM THINKING ABOUT THE LESSONS THAT WE LEARNED FROM STTR AND HOW WE CAME TOGETHER AS A GROUP IN SOME OF THOSE. WE DEVELOPED SOME BEAUTIFUL GUY GIEDING PRINCIPLES FOR COLLABORATION THAT I DEFINITELY WANT TO CARRY FORWARD AND APPLY. >> [INAUDIBLE] >> IT WAS GREAT. AND IT CONTINUES TO BE. WE'RE CONTINUING TO PUBLISH PAPERS FROM THAT COLLABORATION. IT'S BEEN REALLY TREMENDOUS. >> ANY OTHER QUESTIONS? MARY? >> YOUR POINT, IN COMMUNITIES WHERE MAYBE FENTANYL IS NOT VERY PREVALENT BUT COULD BE, IN THE FOLLOWING YEAR, THAT DRAMATIC SHIFT, SOMEHOW, AND I DON'T KNOW HOW YOU BUILD THIS IN TO THE WORK, BUT IF THAT'S TRUE IN A COMMUNITY THAT'S BEING FUNDED, THAT THAT'S ACKNOWLEDGED BECAUSE THINGS HAVE TO SOMETIMES GET WORSE BEFORE THEY CAN GET BETTER AND NOT BE SEEN AS A SETBACK. >> CORRECT. AND SO WE WILL NEED TO HAVE THE TYPE OF DATA THAT WILL ALLOW US TO TRACK ANY KIND OF CHANGE, IT COULD BE THE PRESENCE OF SIN THEY TICS, IT COULD BE THE LOSS OF HEALTH COVERAGE, IT COULD BE A NEW EMPLOYER COMING IN AND GIVING PEOPLE VIABLE EMPLOYMENT. IT COULD BE A POSITIVE TOO, BUT YES, WE CAN HAVE DIFFERENT THINGS THAT WILL IMPACT THE OUTCOMES. >> THANK YOU. >> REDONNA, THANKS VERY MUCH. [APPLAUSE] WITH THAT, WE GO INTO THE EXOANT OF COMPONENT OF THE CONCEPT CLEARANCES. DR. TANYA RAMI IS GOING TO BE GIVING THE PRESENTATION FOR THIS CONCEPT. >> IT'S CONCEPT CLEARANCES TIME. I JUST WANT TO BRING YOU ALL BACK INTO THE AREA OF REAL DRUG DEVELOPMENT. THIS IS THE CONCEPT THAT HAS BEEN PUT FORWARD BY DIVISION OF THERAPEUTICS AND MEDICAL CONSEQUENCES, AND THIS IS ABOUT SUPPORT FOR LABORATORIES FOR EARLY CLINICAL EVALUATION OF PHARMACOTHERAPIES FOR SUBSTANCE USE DISORDERS. FIR OF ALL IT'S GOOD TO GIVE EVERYBODY A LEG LITTLE BACKGROUND AND JUSTIFICATION FOR THIS CONCEPT BEING PUT FORWARD. WE FELT THAT THERE'S AN URGENT NEED, ESPECIALLY IN CURRENT ENVIRONMENT, FOR SPECIALIZED LABORATORIES WITH KNOWLEDGE AND EXPERTISE TO TIMELY AND EFFICIENTLY CONDUCT PHASE 1 AND PHASE 2 CLINICAL TRIALS IN SUBSTANCE USE DISORDERS. AND YOU KNOW, THERE ARE SOME PECULIARITIES IN HOW DRUG DEVELOPMENT GOES ABOUT FOR SUBSTANCE USE DISORDERS, AND ACTUALLY THAT ONLY UNDERSCORES THE NEED FOR SUCH LABORATORIES. PHASE 1 CLINICAL TRIALS, THEY COULD, FOR EXAMPLE, IN SUBSTANCE USE DISORDERS, THEY MUST EVALUATE FIRST OF ALL THE MEDICAL SAFETY OF THE COMPOUNDS BEING TESTED, ESPECIALLY IN COMBINATION WITH ABUSED SUBSTANCE. OTHER AREAS OF DRUG DEVELOPMENT OUTSIDE OF ADDICTION WHICH IS NOT A MUST. SO THEN ALSO PHASE 1 TRIALS AT THE SAME TIME COULD INVOLVE SINGLE, MULTIPLE STUDIES, AND THIS IS NOT EXHAUSTIVE, YOU KNOW, THERE COULD BE OTHER CLINICAL TRIALS DURING THE PHASE 1. PHASE 2 CLINICAL TRIALS, THEY'RE KIND OF BROADER, AND THEY START TO FOCUS ON SAFETY AND EVEN ON EARLY EFFICACY OF THE COMPOUNDS. THIS STUDY IS CONDUCTED IN OUTPATIENT SETTINGS AND TREATMENT-SEEKING POPULATIONS, AND THEY MIGHT NOT REQUIRE THAT STRINGENCY IN TERMS OF MEDICAL SAFETY THAT IS PRESENT DURING PHASE 1 CLINICAL DEVELOPMENT DEVELOPMENT, FOR EXAMPLE, INPATIENT UNIT, WHERE YOU NEED TO HAVE ALL EQUIPMENT AVAILABLE IN CASE SOMETHING HAPPENS. HERE, YOU COULD CONTACT OUTPATIENT SETTINGS BUT STILL YOU ARE IN EXPLORING STAGE. SO YOU'RE GOING TO HAVE TO RUN AN EXPERIMENT, YOU ARE GOING TO HAVE VERY STRINGENT INCLUSION CRITERIA AND YOU'RE GOING TO FOCUS ON SPECIFIC TREATMENT BEFORE YOU CAN GO AND GENERALIZE IT FURTHER INTO PHASE 3. SO OUR GOAL IS TO INCREASE THE AVAILABILITY OF SUCH LABORATORIES, THOSE WHO WOULD BE ABLE KIND OF -- WELL PHASE 1 AND 2 CLINICAL TRIALS, AND THIS IS NOT AN EASY TASK, SO OF COURSE WE'LL DO THAT BASED ON MERIT, AND THERE ARE SOME EXPECTATIONS THAT ARE PRETTY STRINGENT. EACH LABORATORY WE EXPECT TO BE GCP-COMPLIANT, WE EXPECT THEM TO HAVE EASY ACCESS TO IRB, AND THEY MUST HAVE A TRACK RECORD OF SUCCESS IN OPERATIONAL ASPECTS, WHICH IS NOT AN EASY TASK. THEY CANNOT JUST -- THEY NEED TO BE GOOD ENROLLERS, AND THEY NEED TO ENROLL POPULATIONS THAT ARE NOT SEEKING TREATMENT AND THOSE FROM THOSE POP LAYINGS WHO ARE POPULATIONS WHO ARE SEEKING TREATMENT IN PHASE 2. SO THE OTHER THING THAT THEY NEED TO BE ABLE TO COMPLETE CLINICAL STUDIES, CLINICAL TRIALS, WITH STANDARDS AND TIME LINES COMPARABLE TO THE PHARMACEUTICAL INDUSTRY, WHICH IS ALSO SEPARATE BUT VERY IMPORTANT ISSUE THAT YOU CANNOT DRAG SOMETHING FOR 18 MONTH IF YOU HAVE A SMALL STUDY BECAUSE TRIAL -- THE CHARACTER OF THE TRIAL CHANGES AND THEN THE RESULTS MAY NOT BE -- MAY NOT REPLICATE AS A RESULT. ALSO WE'RE KIND OF VERY FOCUSED ON ACTION AND NOT ALLOWING LABORATORIES TO BE IDLE. THEY NEED TO BE CONSTANTLY WORKING. WE HAVE PUT THAT FORWARD THAT AT THE MOMENT, WHEN THEY MOVE FORWARD WITH THE LABORATORY, AT THIS POINT, THEY MUST HAVE ONE OR TWO CLINICAL TRIALS WITH COMPOUNDS READY TO START. THIS IS MY LAST SLIDE AND THIS IS KIND OF TO EMPHASIZE THE GOALS. THE GOAL IS TO PROVIDE SUPPORT FOR BASIC RESOURCES AND SERVICES NECESSARY TO CONDUCT PHASE 1, AND PHASE 2 TRIALS, ANDS A I SAID, I WILL EMPHASIZE AGAIN, THOSE RESOURCES, THEY SHOULD HAVE THE INPATIENT UNION, THEY SHOULD HAVE ACCESS TO PEOPLE WHO ARE SEEKING TREATMENT, NOT SEEKING TREATMENT, AND THEY SHOULD HAVAGING NECESSARY FOR PHASE 2 IN THE CONTEMPORARY DRUG DEVELOPMENT, ALSO STAND ALONE SITE OR COORDINATING CENTER. THAT MEANS THAT WE ARE EMPLOYING THE PRINCIPLE OF HUB AND SPOKES. SO THEY COULD BE A HUB AND THEN THERE COULD BE OTHER SIDES, KIND OF LIKE AN AIRLINE, THEY HAVE A HUB AND THEY HAVE OTHER SITES. BUT THOSE LABORATORIES, THEY EACH SHOULD HAVE ALSO THE INFRASTRUCTURE AND OPERATIONAL CAPABILITIES, BUT THOSE SITES, AT LEAST THEY SHOULD BE OPERATIONALLY VERY AGILE. AGAIN, WE ARE TRYING TO REDUCE OR EVEN ELIMINATE PERIODS OF INACTIVITY. WITH THAT, WE PUT FORWARD AN EXPECTATION THAT EACH LABORATORY WILL PARTICIPATE AT LEAST IN ONE CLINICAL TRIAL GIVEN TIME WITHOUT AN ACTIVITY PERIOD. AND WITH THAT COMES THE MOST -- ONE OF THE MOST IMPORTANT REQUIREMENTS, IS THAT DMEUNDZ COULD COME UP FROM ACADEMIA, FROM INDUSTRY OR GOVERNMENT SPONSORS. THIS IS THE MOST CRITICAL BECAUSE FROM WHERE THOSE PERIODS OF INACTIVITY COME FROM, THEY COME FROM DIFFICULTIES IN OBTAINING THOSE COMPOUNDS. AND SO WE ARE PLANNING TO SELECT THOSE WHERE THEY COULD HAVE THAT STREAM OF COMPOUNDS AND WE, OF COURSE, WILL SET UP THE STRUCTURES THAT COULD HELP THEM TO ACCOMPLISH THAT. THERE WON'T BE MANY OF THOSE LABORATORIES, THERE WILL BE A FEW, AND AS I SAID WE WILL USE THE KIND OF HUB AND APPROACH SPOKE APPROACH TO THAT, BUT SETTING UP THOSE CENTERS THAT WE COULD UTILIZE THEIR BROAD RANGE OF POTENTIAL SOURCES WHERE THOSE COMPOUNDS ARE COMING FROM. OF COURSE THEY COULD BE NORMAL COMPOUNDS AND ALSO -- COMPOUNDS, AND THEY WOULD ENTER CLINICAL DEVELOPMENT AT THE LATER STAGE, THE NEW CHEMICAL ENTITIES WILL ENTER THE PHASE 1, ET CETERA, AND THIS IS MY LAST SLIDE, I THINK I HAVE COVERED ALL, AND NOW I'M OPEN FOR QUESTIONS. [APPLAUSE] >> THANKS VERY MUCH. QUESTIONS? TANYA, THANKS INVESTMENT THE SECOND CONCEPT CLEARANCE IS GOING TO BE PRESENTED BY VIRTUAL REALITY TOOLS, EVIDENCE BASED TREATMENTS OF SUBSTANCE DISORDERS. >> THANK YOU, NORA, FOR THE INTRODUCTION. I'D LIKE TO BRING YOU TO THE SPACE OF SCIENCE IMPLEMENTATION AND POTENTIAL CUSTOMIZATION. AND IT'S MY PLEASURE TO PRESENT THE TOM IK FOR THE SMALL BUSINESS PROGRAM. AT THE BEGINNING, I'D LIKE TO ACKNOWLEDGE MY COLLEAGUES FROM DESPAR BECAUSE THEY INITIALLY PROPOSED AND DEVELOPED THE VIRTUAL REALITY CONCEPT FOR THEIR CONTRACTS IN 2016. OVER THE LAST FEW YEARS, WE SEE LANDSCAPE FOR DIGITAL TECHNOLOGY HAS SIGNIFICANTLY CHANGED. SO THIS IS WHY WE LIKE TO REVISIT THIS TOPIC AND LIKE TO BRING ATTENTION OF FULL POTENCY OF THIS TECHNOLOGY AND WE'D LIKE TO PROPOSE THIS TOPIC AS GRANT INITIATIVES BASED ON THE LESSONS WHICH WE LEARN. YOU DON'T HEAR? OH. OKAY. SORRY. AS YOU KNOW CURRENTLY, THERE ARE SEVERAL TYPES OF DIGITAL TECHNOLOGY GEES THAT CAN FACILITATE TREATMENT AND ENHANCE EVIDENCE-BASED PRACTICE, SPECIFICALLY APPLICABLE FOR RURAL AREAS AND UNDERSERVED POPULATIONS. THE EXAMPLES OF THIS TECHNOLOGY, TELEMEDICINE, COMMUNICATION SUPPORT, TO WEB-BASED OR MOBILE INTERVENTIONS. BUT BY NOW, PROVIDERS BECOME MORE INTERESTED IN TECHNOLOGY, BECAUSE WE SEE THE PATH, THIS MAY HAPPEN AFTER NEW FDA AND CMS GUIDELINES FOR DIGITAL TOOLS AND DIGITAL HEALTH. HOWEVER, TO FULLY ADAPT TECHNOLOGY, WE HAVE A CHALLENGE TO SUSTAIN PATIENT ENROLLMENT AND ENGAGEMENT TO THIS TECHNOLOGY. WE BELIEVE WHAT VIRTUAL REALITY HAS THE POTENTIAL TO SOLVE THIS PROBLEM, BECAUSE VIRTUAL REALITY REALITY -- IT CAN RE-CREATE SOME ELEMENTS OF SOCIAL SITUATION AND BEHAVIORAL ENVIRONMENT FOR THE PATIENT AND RESPOND WHICH THEY CAN ADAPT IN REAL LIFE SITUATION, SO ALSO VIRTUAL REALITY CAN HELP THEM TO EXPERIENCE AND CAN ADOPT NEW LIFE SKILLS TOOLS. SO AS TREATMENT APPROACHES, WE THINK THEY CAN ADOPT VIRTUAL REALITY AND WE CAN EXTEND THIS TOOL EVEN TO TREAT -- FOR TREATMENT OF CHRONIC PAIN. IN ADDITION, I'D LIKE TO MENTION VIRTUAL REALITY MIGHT BE A GREAT TOOL FOR THE CLINICAL RESEARCH STUDIES, BECAUSE IT CAN HELP TO GENERATE DIGITAL MARKETERS OR PATIENT DIGITAL PHENOTYPE AND HELP RESEARCHERS TO MODEL THE SITUATION. SO WHY TO PROPOSE THIS INITIATIVE FOR SMALL BUSINESS FIRST WE HAVE EVIDENCED WITH VIRTUAL REALITY DEFINITELY CAN ENHANCE EVIDENCE-BASED PRACTICE, AND THIS WAS DETERMINED AND EVALUATED IN THE DOMAIN OUTSIDE OF SUD FOR DIFFERENT HEALTH CONDITIONS INCLUDING OBESITY, PTSD, ANXIETY AND DIFFERENT DISORDERS, SO WE TRULY BELIEVE THIS TECHNOLOGY AND THIS SUCCESS MIGHT BE ADOPTED TO SUD FIELD. THE SECOND POINT IS VIRTUAL REALITY IS FULLY SCALABLE, BECAUSE BEFORE IT WAS HIGHLY EXPANSIVE BUT NOW WITH NEW REGULATION AND TECHNOLOGY IMPROVE, WE SEE VARIOUS MARKETING STRATEGIES, SO WE SEE POTENTIAL FOR PRESCRIBEING OR FOR DIGITAL TOOL AND WE SEE THE WAY OF THE REIMBURSEMENT, SO WE HAVE THREE FORWARD PATHS WITH HE SEE OPPORTUNITY FOR SMALL BUSINESS TO COMMERCIALIZE A PRODUCT. AND BASED ON ABOVE STATEMENT, WE HAVE ALREADY PIPELINE OF INVESTIGATORS, COMPANIES, THAT MIGHT -- TO THE SUD SPACE. SO WE NEED TO USE THE POTENTIAL. WA WE NEED FROM THE SMALL BUSINESS TO INTEGRATE AND ENHANCE BEST PRACTICE TO THE REAL CLINICAL PRACTICE? WE'RE LOOKING FOR DATA, VIRTUAL REALITY CAN ENHANCE EVIDENCE BASED PRACTICE. WE'RE LOOKING FOR AND WE NEED THE PLATFORMS FOR PROVIDERS TO MANAGE VIRTUAL REALITY EXPERIENCE OF PATIENTS. ENDING IN SOLUTIONS THAT STRUCTURALLY WILL CHALLENGE SUCH FOR REGULATION, REIMBURSEMENT, POTENTIAL INTEGRATION INTO ELECTRONIC MEDICAL RECORDS, WE NEED A GOOD SOLUTION AND I THINK SMALL BUSINESS WILL BE CAPABLE TO DO IT. WE BELIEVE FOR ALL THIS AND ALL THE NEWS THAT FACILITATED THE PIPELINE WILL HELP SMALL BUSINESS TO DEVELOP TECHNOLOGY AND ALL THOSE REQUIREMENTS WILL BE FULLY ACHIEVABLE. SO WITH THAT, I WOULD LIKE TO THANK YOU FOR YOUR ATTENTION AND I'M READY FOR YOUR QUESTIONS. [APPLAUSE] >> ANY QUESTIONS? >> HI. WITH VIRTUAL REALITY AS FAR AS CONVERSATION IN THE ROLE OF TREATMENT, ARE YOU SAYING THE MORE RURAL COMMUNITIES AS A MAJOR TARGET? >> WE SEE THE EVIDENCE WITH TECHNOLOGY BEING APPLIED FOR RURAL COMMUNITY, BUT WE'RE NOT LOOKING FOR LIMITATION ONLY FOR RURAL COMMUNITY. WE ARE LOOKING TO EXPAND. I GAVE THE EXAMPLE BECAUSE THAT'S -- THAT PRINCIPAL IS BEING INTRODUCED AS A SOLUTION FOR A RURAL COMMUNITY, BUT WE'RE REALLY NOT GOING TO LIMIT IT ONLY BECAUSE I THINK THIS TOOL CAN BE EXPANDED TO ANYONE, ANY TREATMENT PROTOCOLS. >> OK. I AGREE, BECAUSE I JUST -- I'M NOT AWARE OF ANY RESEARCH THAT SHOWS THAT THIS PARTICULAR PLATFORM IS READILY ADAPTED IN A RURAL COMMUNITY. >> YES, BECAUSE WE TALK ABOUT TECHNOLOGY IN DIFFERENT DISEASES AND DIFFERENT FIELDS, AND IDEALLY FOR SUD BUT WE WOULD LIKE SMALL BUSINESS TO WORK ON THAT. BECAUSE NOW, TECHNOLOGY WILL ALLOW US TO DO IT BECAUSE TECHNOLOGY IS MOVING SO FAST. >> THANK YOU. >> ANY OTHER QUESTIONS? THANKS VERY MUCH. >> THANK YOU. [APPLAUSE] NOW WE COME TO THE STAGE OF THE MEETING THAT IS OPEN FOR PUBLIC COMMENTS, SO IF THERE'S ANYONE THAT WANTS TO MAKE A PUBLIC COMMENT, THE MICROPHONE IS THERE. PLEASE IDENTIFY YOURSELF, WHO YOU BELONG TO, AND LIMIT YOUR REMARKS TO LESS THAN FIVE MINUTES. I DON'T THINK THERE ARE ANY PUBLIC COMMENTS, IN WHICH CASE I CAN THEN END THE DAY BY THANKING YOU ALL FOR YOUR INPUT AND I LOOK FORWARD TO SEEING YOU NEXT TIME. AND IN THE MEANTIME, AS WE DEPLOY THE HEAL INITIATIVES, PLEASE BE UP FRONT AND PROACTIVE IN TERMS OF WHAT YOU THINK WOULD BE VALUABLE. WE DEPEND ENORMOUS IN THE SCIENTIFIC COMMUNITY, YOU HAVE BEEN CHOSEN BECAUSE OF YOUR EU NOOK PERSPECTIVE, AND BEING IN COUNCIL, IT GIVES YOU AN IDEA OF THE DIFFERENT AREAS OF THE PORTFOLIO WE'RE TRYING TO MOVE. SO PLEASE FEEL FREE AND I ENCOURAGE YOU TO ACTUALLY THINK PROACTIVELY IN TERMS OF THINGS THAT WE MAY NOT BE THINKING THAT COULD BE VALUABLE THAT WE SHOULD. YOU CAN ALWAYS EMAIL ME AND REACH OUT TO ME, NOT JUST WAIT FOR COUNCIL TO COME ALONG. SO I COUNT ON YOU FOR THAT, AND IN THE MEANTIME, I THANK YOU FOR EVERYTHING THAT YOU'VE DONE, AND I WISH YOU A GOOD TRIP BACK HOME, AND THANKS A LOT. [APPLAUSE]