>> WELCOME, EVERYONE. I SEE MEMBERS OF THE HEAL EXECUTIVE COMMITTEE AND MEMBERS OF THE HEAL MULTI-DISCIPLINARY WORKING GROUP JOINING. THANK YOU, ESPECIALLY FROM THE WEST COAST, IT'S A LITTLE BIT EARLY. PARISA, ARE YOU ABLE TO TAKE US THROUGH ROLL. >> I'M HERE. HOPEFULLY YOU CAN HEAR ME. DR. TABAK IS HERE. LET'S SEE. WE HAVE DR. CRISWELL, DR. WEBSTER, DR. LANGEVIN, I SEE VOLKOW. >> DR. NUSSBAUM. >> CAN WE HAVE THE MEMBERS SAY GOOD MORNING AND MAKE SURE THEIR AUDIO WORKS? >> IT WORKS, I'M HERE. >> THANK YOU. >> KEEP GOING. >> DR. DONOFRIO? >> HERE. >> DR. DEBAR? >> HERE, THANKS. >> DR. GARLAND? >> I'M HERE, GOOD TO SEE EVERYONE. >> DR. JARREAU. >> GOOD MORNING, EVERYONE. >> DR. JERNIGAN. >> HI, I'M HERE, GOOD MORNING. >> DR. HENRY? >> GOOD MORNING. >> PERFECT. DR. KUNTZ? NOT ON YET, OKAY. DR. NU„EZ? OKAY. DR. PACE? >> HERE, GOOD MORNING. >> GOOD MORNING. DR. SMITH? >> HI. >> HELLO. AND CHRIS BEASLEY. >> -- CHRIS VEASLEY. >> GOOD MORNING. >> FROM NIH I SEE DR. GORDON ALSO JOINED. LET'S SEE HERE. OKAY. DR. KOROSHETZ IS HERE. HELLO. >> HEY. >> THAT'S PRETTY GOOD. THANK YOU. I WILL EXTEND A WELCOME TO THE MEMBERS OF THE HEAL EXECUTIVE COMMITTEE AND MEMBERS OF THE HEAL MULTI-DISCIPLINARY WORKING GROUP. THANK YOU FOR JOINING US AT THE END OF MAY FOR A BRIEF OPEN SESSION AND UPDATES AND INFORMATION ABOUT PROGRESS OF "HEAL" RESEARCH UNDERWAY. AND THEN WE'LL SWITCH TO CLOSED SESSION, WHERE WE WILL DISCUSS SOME HEAL RESEARCH PROJECTS UNDER CONSIDERATION. I'LL NOW TURN IT OVER TO DR. LAWRENCE TABAK, ACTING DIRECTOR OF THE NATIONAL NATIONAL INSTIF HEALTH, TO START US OFF. GO AHEAD, LARRY. >> THANKS, REBECCA. I APPRECIATE YOUR LEADERSHIP OF THIS RATHER LARGE AND COMPLEX ENDEAVOR, AND I REALLY WANT TO THANK YOUR TEAM AS WELL FOR ALL THAT THEY ARE DOING. WELCOME TO ALL THE MEMBERS OF THE GROUP. I THINK, YOU KNOW, IT'S NOT HYPERBOLE TO SAY THAT "HEAL" RESEARCH IS PROVIDING HOPE TO MILLIONS OF PEOPLE. AND WHAT WE DO WITH THIS WORKING GROUP IS WE SEEK A REALITY CHECK ON WHAT IT IS THAT WE'RE DOING. THIS GROUP IS ONE OF SEVERAL WHICH HELPS ENSURE THAT WHAT WE'RE DOING IS RELEVANT AND ALIGNED WITH THE STATE OF THE SCIENCE. PUBLIC HEALTH CHALLENGE, YOU ALL KNOW ALL TOO WELL, REMAINS URGENT. WE NEED TO BE STRATEGIC ABOUT OUR RESEARCH PROGRAMS. AND WE NEED TO GET RESULTS OUT TO SCIENTISTS AND COMMUNITIES AS QUICKLY AS POSSIBLE. I'M VERY PLEASED "HEAL" CONTINUES TO PUSH FORWARD NIH-WIDE EFFORTS FOR MORE OPEN SCIENCE, AND FOR MORE RAPID DISSEMINATION OF FINDINGS, AND ALL OF YOU CAN HELP US AMPLIFY THESE EFFORTS, AND WE THANK YOU FOR YOUR WILLINGNESS TO DO SO. NOW, AGAIN, I NEED NOT TELL THIS GROUP CHRONIC PAIN REMAINS AN ENORMOUS PUBLIC HEALTH CHALLENGE. AND WE KNOW CERTAINLY THAT CHRONIC PAIN IS JUST NOT A LONGER-LASTING VERSION OF ACUTE PAIN. I THINK WHAT EMERGES IS THAT WHEN YOU'VE SEEN A PATIENT IN CHRONIC PAIN, YOU'VE SEEN A PATIENT IN CHRONIC PAIN. AND THAT SORT OF GENERIC APPROACH WON'T NECESSARILY WORK. AND SO THE WHOLE-PERSON APPROACH THAT "HEAL" HAS EMBARKED ON DOES SEEM TO BE IN SYNCHRONY WITH WHAT WE THINK IS A NEED TO DEVELOP PERSONALIZED TREATMENT PLANS FOR PAIN. JUST A FEW WEEKS AGO, THE NATIONAL CENTER FOR COMPLEMENTARY AND INTEGRATIVE HEALTH PUBLISHED A PAPER ABOUT CHRONIC PAIN IN THE U.S. THE STUDY ANALYZED NATIONAL HEALTH INTERVIEW SURVEY DATA AND FOUND THAT CHRONIC PAIN IS MORE COMMON THAN EITHER DEPRESSION OR DIABETES. AND THAT I THINK REPRESENTS A CLEAR CALL TO ACTION FOR THE IMPORTANT WORK THAT WE'RE ALL DOING TOGETHER TO CONTINUE. UNTREATED PAIN CONTINUES TO BE A TROUBLESOME DRIVER OF OPIOID USE, AND ITS OBVIOUS CONSEQUENCES BUT WE'RE MAKING SOME HEADWAY. SO TODAY YOU'LL HEAR ABOUT PAIN MANAGEMENT RESEARCH THAT INCLUDES THE CONTINUING SEARCH FOR NEW DRUG PAIN -- NEW PAIN TARGETS, DEVELOPING BETTER PAIN MODEL SYSTEMS, AND TESTING DRUG-FREE PAIN MANAGEMENT STRATEGIES. "HEAL" HAS REALLY OPENED UP LOTS OF THINGS TO ADDRESS THIS MAJOR HEALTH PROBLEM, HURDLES ARE MANY. FOR EXAMPLE, INCLUDING FIGURING OUT HOW TO INCREASE ACCESS TO TREATMENTS THAT WORK, HOW TO PAY FOR THEM, HOW TO BE FAIR AND EQUITABLE. BUT "HEAL" IS ALSO WELL POSITIONED TO ADDRESS THESE CHALLENGES AS WELL AT MYRIAD OF WORKFORCE-RELATED ISSUES. "HEAL" HAS RECENTLY STOOD UP SEVERAL TRAINING PROGRAMS FOR INNOVATEIVE RESEARCH FOR ADDICTION AND PAIN. ONE IS THE SO-CALLED PURPOSE NETWORK, WHICH IS A BRAND-NEW NATIONAL PAIN RESEARCH NETWORK, BY CONNECTING PAIN SCIENTISTS FROM ALL DISCIPLINES AT VARIOUS CAREER STAGES, "HEAL" IS FILLING A MAJOR GAP BY DEVELOPING AND NURTURING A COMMUNITY OF PRACTICE AND MUTUAL LEARNING. AND JUST LAST WEEK A STUDY FUNDED BY THE NIH BRAIN INITIATIVE, HEAL, AND DARPA REPORTED ON BRAIN SIGNATURES FOR CHRONIC PAIN AND A SMALL NUMBER OF FOLKS USING SURGICALLY IMPLANTED ELECTRODES, TARGETING THEIR ANTERIOR CINGULATE CORTEX AND ORBITAL FRONTAL CORTEX, AS THE PARTICIPANTS ACTUALLY REPORTED ON CURRENT LEVELS OF PAIN. IT REALLY OPENS YOU WILL A WHOE NEW SET OF THINGS THAT CAN BE DONE IN THE FUTURE. THE FEDERAL RESPONSE, BECAUSE "HEAL" IS AN NIH-WIDE INITIATIVE DOES BENEFIT FROM A LARGE AND DIVERSE RESEARCH PORTFOLIO THAT IS SUPPORTED BY MANY OF THE NIH INSTITUTES AND CENTERS. AS YOU KNOW, NIH WORKS VERY CLOSELY WITH OUR FEDERAL PARTNERS, INCLUDING THE CDC, FDA, SAMHSA, DEA, AND OTHERS. SCIENTIFIC SOLUTIONS ARE REALLY IMPORTANT TO INFORM UNMET MEDICAL NEEDS, BUT CLEARLY LAWS AND POLICY INFORMED BY SCIENCE ARE ALSO CRITICAL. WE MEET MONTHLY WITH OUR FEDERAL PARTNERS AND OUR WORK TOGETHER WE FEEL IS HAVING AN IMPORTANT IMPACT ON THE NATIONAL LANDSCAPE ON WHICH HEAL RESEARCH IS CONDUCTED. AS YOU'VE HEARD IN MARCH, THE FDA APPROVED OVER THE COUNTER NALOXONE, AN IMPORTANT STEP GUIDED BY A PRODUCTER FEDERAL RESPONSE INCLUDING OUTREACH TO STATES THROUGH SAMHSA, AND WORK IS UNDERWAY TO FIGURE OUT HOW TO INCREASE ACCESS TO THIS LIFE-SAVING MEDICATION. UNFORTUNATELY COST REMAINS A BARRIER. AND SOME RESEARCHERS ARE USING THESE INNOVATIVE APPROACHES TAKING ADVANTAGE OF A.I. AND SOCIAL MEDIA TO SEE IF THEY CAN FIGURE OUT BETTER WAYS TO TRACK OVERDOSE AND DRUG USE PATTERNS SO THEY CAN MAP THE PLACE WHERE HELP IS MOST NEEDED. NOW, IN ADDITION, JUST LAST WEEK FDA APPROVED TWO NEW MEDICATIONS TO HELP PEOPLE KEEP SAFE AND FIND LONG-TERM RECOVERY. ONE IS A NALOXONE ALTERNATIVE, A NASAL SPRAY VERSION OF NALOPHANE THAT CAN QUICKLY RESUSCITATE USERS AND PROTECT FROM RELAPSE, USED FOR DECADES TO REVERSE OVERDOSES OF HEROIN, FENTANYL, AND PRESCRIPTION PAIN KILLERS, AND THIS UNLIKE NALOXONE ENTERS THE BRAIN VERY QUICKLY AND REMAINS LONGER IN THE BODY. THE SECOND APPROVAL PROVIDES A NEW BUPRENORPHINE DOSING OPTION, SPECIFICALLY THE FDA APPROVED THE EXTENDED RELEASE BUPRENORPHINE INJECTION TO TREAT MINOR TO SEVERE OPIOID USE DISORDER, AVAILABLE IN DIFFERENT FORMULATIONS THAT COULD BE ADMINISTERED WEEKLY OR MONTHLY, REFLECTING A REAL AND MEANINGFUL COLLABORATION ONGOING BETWEEN THE NIH AND THE FDA. BUT OBVIOUSLY WE CAN'T JUST REST ON THESE RECENT SUCCESSES. THERE ARE MANY NEW THREATS LIKE XYLAZINE AND DRUG COMBINATIONS THAT MAKE OUR ONGOING WORK CHALLENGING AN UNPREDICTABLE. XYLAZINE IS A MAJOR CHALLENGE FOR PUBLIC HEALTH. THIS NON-OPIOID ANIMAL TRANQUILIZER, HENCE THE NICKNAME TRANQ ON THE STREET IS MIXED WITH OTHER DRUGS SUCH AS FENTANYL ARE NO GOOD ANTIDOTE FOR THIS. IT CAN LEAD TO SERIOUS TISSUE DAMAGE AT THE INJECTION SITE. PREVIOUSLY XYLAZINE WAS MAINLY USED IN A FEW CITIES ON THE EAST COAST BUT NOW THIS DEVASTATING DRUG HAS SPREAD RAPIDLY ACROSS THE COUNTRY. JUST LAST MONTH THE WHITE HOUSE OFFICE OF NATIONAL DRUG CONTROL POLICY DESIGNATED FENTANYL ADULTERATED WITH XYLAZINE AS AN EMERGING THREAT. THE BIDEN ADMINISTRATION WILL BE RELEASING A RESPONSE PLAN AND IMPLEMENTATION GUIDANCE TO ADDRESS THIS THREAT. THE PLAN WILL INVOLVE TESTING, EPIDEMIOLOGY, PREVENTION, TREATMENT, AND CARE, AS WELL AS THE NECESSARY DATA SYSTEMS AND STRATEGIES TO ADDRESS SUPPLY CHAIN ISSUES. THE PLAN WILL CALL FOR COLLABORATION ACROSS FEDERAL AGENCIES AND WILL CALL FOR RESEARCH, INCLUDING STUDIES TO UNDERSTAND INTERACTION BETWEEN FENTANYL AND XYLAZINE. FEDERAL POLICY CERTAINLY AFFECTS "HEAL" RESEARCH AND THE POPULATION RESEARCH AND POLICY SURROUNDING TELEHEALTH LOOM LARGE. NOW, MEMORIES OF THE PANDEMIC LIFE ARE STILL VERY FRESH IN ALL OF OUR MINDS, AND MANY PEOPLE HAVE COME TO APPRECIATE THE FLEXIBILITY OF THE VARIOUS TELEHEALTH PLATFORMS FOR RECEIVING CARE FROM PHYSICIANS AND OTHER HEALTH CARE PROVIDERS TO ACCESS MEDICATIONS AND MENTAL HEALTH TREATMENT. YOU MAY HAVE HEARD THAT THE DEA IN CONCERT WITH HHS ISSUED A TEMPORARY RULE EXTENDING ALL THESE FLEXIBILITIES BUT TELEHEALTH PRESCRIBING SERVICES THROUGH NOVEMBER 11 INCLUDES BOTH PRESCRIPTION OF METHADONE AND BUPRENORPHINE. DEAE AND HHS HOSTED A TOWN HALL IN MARCH TO DISCUSS BUPRENORPHINE AVAILABILITY WITH PHARMACEUTICALS ORGANIZATIONS, WHOLE WHOLESALERS. TELEHEALTH IS A FLUID ENVIRONMENT THAT WILL BENEFIT FROM RESEARCH AND POLICY PRACTICE, AND NO DOUBT WHEN THIS GROUP MEETS AGAIN WE'LL HAVE AN UPDATE ON THE STATUS OF TELEHEALTH. WHEN YOU MET IN FEBRUARY YOU HEARD ABOUT NEW LEGISLATION THAT AFFECTS THE CONTEXT OF "HEAL" RESEARCH, THE MAINSTREAMING ADDICTION TREATMENT ACT AND MEDICATION ACCESS AND TRAINING EXPANSION ACT PROVIDED HISTORIC FUNDING FOR MENTAL AND BEHAVIORAL HEALTH PROGRAMS. THE LAWS WILL UPDATE TRAINING REQUIREMENTS FOR CLINICAL WORKERS, AND PUT MORE DOLLARS INTO THE GROWING BEHAVIORAL HEALTH WORKFORCE WHICH AS YOU ALL KNOW IS UNDER SEVERE STRESS. "HEAL"'S EFFORTS TO STRENGTHEN THE PAIN WORKFORCE ARE AN IMPORTANT ADJUNCT TO THESE NEW LAWS. NOW, TO CONCLUDE, THE NATIONAL CRISIS OF UNDERTREATED PAIN SUBSTANCE USE AND OVERDOSE IS A SIGNIFICANT CHALLENGE, TO BE SURE. SEEMS THAT EVERY FEW MONTHS A NEW WRINKLE EMERGES, COMPLICATED AN ALREADY COMPLEX SUITE OF HEALTH CONDITIONS, INFLUENCED BY OF COURSE MANY SOCIETAL FACTORS. WHAT RESEARCHERS HOPE, IT IS IMMENSELY GRATIFYING TO SEE MAJOR RESULTS NOW COMING THROUGH, AND REBECCA WILL SHARE MANY OF THESE WITH YOU SHORTLY. THROUGH THE POWER OF SCIENCE AND EMPOWERING COMMUNITIES, "HEAL" IS MAKING A DIFFERENCE IN LIVES OF INDIVIDUALS AND COMMUNITIES ACROSS THE NATION. I WANT TO THANK YOU AGAIN FOR YOUR TIME, FOR YOUR TALENT, AND YOUR DEDICATION TO THESE PROGRAMS. WE CERTAINLY RELY ON YOU TO HELP ENSURE THAT WE'RE ON THE BEST PATH FORWARD, TO ACHIEVE THE "HEAL" MISSION OF ENDING ADDICTION LONG TERM. AND SO WITH THAT I THANK YOU AND, REBECCA, I WILL TURN IT BACK TO YOU. >> THANK YOU SO MUCH, DR. TABAK. IT'S NOW MY PLEASURE TO TURN IT OVER TO DR. WALTER KOROSHETZ, DIRECTOR OF THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE. TAKE IT AWAY, WALTER. >> THANKS VERY MUCH, REBECCA. THANKS VERY MUCH, LARRY. AND, YES, I'M GOING TO TALK ABOUT THE OVERVIEW OF THE CLINICAL PAIN REVIEW. NEXT SLIDE. SO, JUST TO -- I'M NOT MUTED, AM I? NO, OKAY. >> WE HEAR YOU. >> OKAY. YEAH, JUST TO GO BACK A SECOND, AS WE STARTED "HEAL," THE PURPOSE WAS TO DEVELOP NON-ADDICTIVE TREATMENTS FOR PAIN, AND THAT WAS DEVELOPING NOVEL TREATMENTS BUT ALSO TESTING THINGS THAT ARE ALREADY, YOU KNOW, IN THE ARMAMENTARIUM TO IMPROVE MANAGEMENT OF PAIN, WHICH LARRY TOLD US HOW BIG A PROBLEM IT IS, BUT ALSO TO REDUCE ADDICTION AS A CONSEQUENCE BECAUSE THAT'S KIND OF HOW WE GOT INTO THE EPIDEMIC OF OPIOID OVERUSE DISORDERS IN THE FIRST PLACE. SO IN THE PAIN SPACE, THE DISCOVERY PART IS DONE PRIMARILY BY THE INSTITUTES. BUT THEN "HEAL" HAS PROGRAMS TO MOVE DISCOVERY THROUGH THE PRE-CLINICAL DEVELOPMENT SPACE, TO DEVELOP A NOVEL THERAPY THAT WOULD HOPEFULLY GET PICKED UP BY INDUSTRY FOLKS AND BROUGHT TO COMMERCIALIZATION. NOW, UNFORTUNATELY, THAT IS A PROBLEM BECAUSE THERE'S VERY LITTLE INTEREST ON THE PART OF THE INDUSTRY DUE TO PREVIOUS FAILURES. BUT THERE ARE BIOTECH COMPANIES IN THIS SPACE, AND WE'RE HOPING TO DE-RISK SOME OF THIS PROCESS SO EVENTUALLY PATIENTS WILL SEE MUCH MORE EFFECTIVE TREATMENTS FOR CHRONIC PAIN THAT DON'T CAUSE ADDICTION. BUT IN THAT SPACE WE DO SOME CLINICAL TRIALS, SAY EPPIC-NET PHASE 2 STUDY OF NOVEL THERAPIES, WE ARE DOING CLINICAL TRIALS TO TEST DIFFERENT WAYS MANAGING DIFFERENT TYPES OF PAIN IN A MUCH MORE EFFECTIVE MANNER, AND ALSO IN DOING SO REDUCING THE RISK OF ADDICTION. SO, IN TERMS OF THE SPACES THAT WE'RE IN NOW, WE'RE LOOKING HEAVILY AT CLINICAL BIOMARKERS BECAUSE ONE THING THAT'S KEEPING THE COMPANIES OUT OF THE PAIN SPACE IS THAT THIS RELIANCE ON PAIN ASSESSMENT 1-10 SCALE HOW MUCH PAIN DO YOU HAVE, THERE AREN'T THE KIND OF BIOLOGICAL MARKERS THAT YOU NEED TO TEST YOUR DRUG AGAINST A TARGET TO KNOW IF YOU HAVE TARGET ENGAGEMENT OR PROOF OF PRINCIPLE. SO WE HAVE A BIOMARKER PROGRAM, AGAIN VERY DIFFICULT IN THE PAIN SPACE BUT WE'RE MAKING SOME PROGRESS. NOW, MUSCULOSKELETAL PAIN ESPECIALLY LOW BACK PAIN AND NECK PAIN ARE LEADING CAUSE OF DISABILITY IN THE U.S. AND WE HAVE A PROGRAM BACPAC WHICH IS RUN BY DR. CRISWELL'S INSTITUTE, NIAMS, TRYING TO GET AT THE UNDERLYING DIFFERENT CAUSES OF THIS VERY TROUBLESOME PROBLEM, AND DEVELOPING KIND OF CUSTOMIZED TREATMENTS DEPENDING ON WHAT IS THE NATURE OF THE CONDITION. AS I MENTIONED, WE HAVE THE EPPIC-NET PROGRAM TO BRING THINGS IN USUALLY FROM BIOTECH COMPANIES INTO FIRST-IN-HUMAN TRIALS, A VERY INTERESTING STUDY IN PEOPLE ON DIALYSIS WHO SUFFER PAIN, VERY COMMONLY, TO GET MORE EFFECTIVE NON-ADDICTIVE TREATMENTS. WE HAVE A NUMBER OF EFFECTIVENESS TRIALS, THE EARN NETWORK TESTING DIFFERENT WAYS OF TESTING PAINING WITH PHARMACOLOGICAL, AND A SUITE OF PRAGMATIC TRIALS RUN BY DR. LANGEVIN'S GROUP PRIMARILY, TESTING MOSTLY NON-PHARMACOLOGICAL THERAPIES IN HEALTH CARE SYSTEMS, WE HAVE RESEARCH TO IMPROVE HEALTH EQUITY IN TERMS OF TREATMENT OF PAIN. AND THE BIG PROBLEM IS HOW TO MANAGE PEOPLE WHO HAVE A COMBINATION OF PAIN AND OPIOID OVERUSE DISORDER, OR PAIN AND CHRONIC OPIOID USE. AND A BIG PUSH TO TRY TO MOVE INTO RURAL POPULATIONS WHERE THE PAIN PROBLEM IS ACTUALLY WORSE THAN IT IS IN URBAN AREAS, AND, AGAIN, ACCESS TO THERAPIES IS NOT AS GOOD. A NUMBER OF THINGS THAT WE DO I THINK IS GOING TO REALLY TRANSFORM THE FUTURE OF PAIN RESEARCH. WE'RE DEVELOPING SYSTEMS TO ENGAGE PATIENTS LIKE NEVER BEFORE. OF COURSE FOR PAIN THIS IS SO INCREDIBLY IMPORTANT BECAUSE IT'S THAT EXPERIENCE OF PAIN IS WHAT WE'RE TRYING TO GET AT, AND SUFFERING CAUSED BY THE PAIN NOT NECESSARILY SENSATION OF PAIN BUT THAT SUFFERING THAT GOES ALONG WITH IT. THE PAIN WORKFORCE IS ALSO SOMETHING THAT WE'RE CONCENTRATING ON, PARTICULARLY IN THE CLINICAL SIDE. AS CLINICIANS SPECIALIZING IN PAIN ARE BECOMING QUITE RARE, BUT YET THE RESEARCH THAT'S COMING OUT OF THE DISCOVERY PAIN SCIENCE IS REALLY QUITE STRIKING, ADVANCED, TRYING TO MATCH UP A CLINICAL WORKFORCE THAT CAN TAKE ADVANTAGE OF THESE EXPLOSIONS IN THE NEUROSCIENCE I THINK IS WHAT WE'RE HOPING TO DO. AGAIN, WE'RE TRYING TO IMPROVE THE DIVERSITY OF THE WORKFORCE AND THROUGH ALL THIS THE IDEA IS TO TRY AND BRING ALL THE DATA TOGETHER SO THAT ONE CAN COMPARE ACROSS DIFFERENT PAIN CONDITIONS, DIFFERENT TREATMENTS. SO THIS IS KIND OF THE CLINICAL PAIN PROGRAM IN TOTO AS IT STANDS RIGHT NOW, NOT WITH ALL THE DETAILS BUT IN BROAD STROKES. NEXT SLIDE. THE NEXT SLIDE SHOWS WHERE WE ARE IN TERMS OF TYPE OF PAIN CONDITIONS. IN TERMS OF LOOKING AT THE BIOMARKERS AND THE DIFFERENT BIOMARKER ASSAYS PEOPLE ARE LOOKING AT IN FLUIDS, MULTI-MODALITY BIOMARKERS, EVEN SOME EEG BIOMARKERS, MANY OF THEM GETTING AT PROGNOSTIC, PARTICULARLY IN POST-SURGICAL PAIN WHERE YOU LIKE TO KNOW WHO IS AT RISK FOR DEVELOPING POST-SURGICAL PAIN AND POTENTIALLY DO SOMETHING TO PREVENT IT. THANKS TO HELENE LANGEVIN WE HAVE AN AMBITIOUS PROGRAM LOOKING AT MYOFASCIAL TISSUES AND THE CAUSE OF PAIN THERE. VERY UNDERSTUDIED AREA. I HAVE EXPERIENCE IN IT PERSONALLY, AND IT'S NOT FUN. BUT WHAT CAUSES IT IS REALLY QUITE A MYSTERY. YOU KNOW, IT'S THE JOINTS, MUSCLES, FASCIA, ASSOCIATED SOFT TISSUES, AND REALLY GETTING AT THIS IN A WAY THAT'S NEVER BEEN ACCOMPLISHED BEFORE, PARTICULARLY IN GETTING BIOMARKERS OF THE CONDITION, WE'RE USING THINGS LIKE ULTRASOUND, PET, ELECTROPHYSIOLOGY, M.R., MEASUREMENTS OF STIFFNESS, O2 PERFUSION, MARKERS OF FIBROSIS, PARTICULARLY ULTRASOUND, BRINGING INTO MULTI-SCALE MODELING TYPE OF ENVIRONMENT IS POTENTIALLY GOING TO BE TRANSFORMATIVE, HOW WE THINK ABOUT IT. THE MOST COMMON PAIN CONDITION IS MUSCULOSKELETAL PAIN CONDITIONS. NEXT SLIDE. HELENE WILL CORRECT ME IN I MADE MISTAKE, EPPIC-NET HAS WHO TRIALS ONGOING, ARTHRITIS AND DIABETIC PRIVILEGE NAIL -- PERIPHERAL NEUROPATHY, THERE'S INTEREST ON A BUNCH OF COMPANIES OUT THERE TO TEST THEIR THERAPIES IN THIS DIABETIC PERIPHERAL NEUROPATHY CONDITION. NEXT SLIDE. THIS IS GOING TOWARDS EFFECTIVENESS RESEARCH NETWORK, RUN HEAVILY OUT OF NCATS AND JANE ATKINSON I SHOULD HAVE MENTIONED FROM THE BEGINNING ALL THESE PROGRAMS ARE RUN BY TEAMS, THAT HAVE PROGRAM DIRECTORS FROM MULTIPLE INSTITUTES ON THEM, AND JANE ATKINSON AND LINDA PORTER ARE KIND OF THE CHAIRS OF THOSE TEAMS, AND THAT'S WHERE THE PEOPLE HERE WHO ARE DOING ALL THE WORK. IN THE EFFECTIVENESS RESEARCH SPACE WE HAVE LOOK -- LOOKING AT DIFFERENT TRIALS ON A NUMBER OF CONDITIONS, ACTUALLY ARTHRITIS, POST-CESAREAN, POST MASTECTOMY, CHRONIC MUSCULOSKELETAL, RURAL AREAS, CHRONIC PAIN AND OUD, CANCER PAIN, PERIOPERATIVE PAIN IN ADULTS AND ADOLESCENTS, IF YOU FACTOR IN ACUTE TO CHRONIC PAIN PROGRAM BEING RUN OUT OF THE COMMON FUND. THE INTERVENTIONS ARE STEPPED UP MEDICAL INTERVENTIONS AS MIGHT OCCUR IN THE PRACTICE SITUATION, SHARED DECISION MAKING AND USE OF OPIOIDS AND REALLY CAUTIOUS AND DELIBERATE MANNER, DRUG INTERVENTIONS, DRUG AND BEHAVIORAL INTERVENTIONS, AND BEHAVIORAL INTERVENTIONS. NEXT SLIDE. IN THE PRAGMATIC STUDIES, AGAIN HEAVILY RUN OUT OF NCCIH, IN FACT HELENE LANGEVIN'S INSTITUTE, LOOKING AT NERVE STIMULATION, PHYSICAL THERAPY, ACUPUNCTURE, RELAXATION, MINDFULNESS, DECISION SUPPORT, MOSTLY NON-PHARMACOLOGICAL TREATMENTS IN THESE DIFFERENT PAIN CONDITIONS AND MANY ARE RUN IN HEALTH CARE SYSTEMS, EFFECTIVENESS RESEARCH NETWORKS ARE PRIMARILY IN ACADEMIC INSTITUTIONS. NEXT SLIDE. HERE YOU SEE THE DIFFERENT PAIN CONDITIONS AND NUMBER OF AWARDS AND DIFFERENT PAIN CONDITIONS, SO THEY ARE PRETTY MUCH ALL CHRONIC PAIN, NOT DOING A LOT IN THE ACUTE PAIN SPACE, BUT BECAUSE CHRONIC PAIN AS LARRY MENTIONED IS THE PROBLEM AT HAND THAT GETS YOU INTO TROUBLE WITH OPIOIDS BUT ALSO IS WHAT CAUSES THE LONG-TERM SUFFERING. BACK PAIN IS SEVERAL AS I MENTIONED THE BIGGEST OF ALL. POST-SURGICAL PAIN, CANCER PAIN, TRAUMA PAIN, PARTICULARLY OF INTEREST TO NIDCR IS TEMPOROMANDIBULAR DISORDER. AGAIN, FOCUSING SIMILARLY IN ON WHAT WE TALKED ABOUT WITH MYOFASCIAL PAIN, WHERE YOU HAVE A VERY COMPLEX JOINT, YOU HAVE MULTIPLE DIFFERENT TISSUES INVOLVED, MUSCLE, FASCIA, NERVED, AND IS A FOCUS OF A NUMBER OF OUR PROGRAMS. WE ALSO HAVE PROGRAMS IN SICKLE CELL DISEASE, A VERY COMMON PAIN CONDITION, AND ONE WHICH DOES REQUIRE OPIOIDS TO TREAT THE ACUTE STAGES. SO, KIND OF THREADING THAT NEEDLE OF GETTING REALLY GOOD EFFECTIVE PAIN CONTROL, AND REDUCING THE CHANCE OF ADDICTION IS A REAL CHALLENGE BUT ONE THAT'S REALLY BEEN TAKEN ON BY A NUMBER OF PROJECTS IN THE HEAL INITIATIVE. NEXT SLIDE. AND THE INTERVENTIONS, WE MENTIONED IN THE PREVIOUS SLIDE WHAT THE INTERVENTIONS ARE. THE SETTINGS, YOU KNOW, MAJORITY ARE DONE IN THE OUTPATIENT CLINIC, CERTAINLY CHRONIC PAIN IS PRIMARILY GOING TO BE SEEN IN THE OUTPATIENT CENTER. ACADEMIC MEDICAL CENTERS ARE, YOU KNOW, THE DRIVERS OF RESEARCH IN OUR SYSTEM HERE, LARGELY OUTPATIENT CLINIC BASED AND BASED OUT OF HOSPITALS, PRIMARY CARE. WE HAVE A PRETTY INTERESTING COMPONENT OF TELEHEALTH, PARTICULARLY WHEN IT GETS OUT TO GETTING TREATMENTS IN RESEARCH IN THE RURAL SPACE, SOME, AS MENTIONED, PARTICULARLY PRISM PRAGMATIC STUDIES, WE WORK WITH THE V.A. DR. LANGEVIN RUNS A PROGRAM IN PAIN WITH THE DoD AND V.A. HERE IS THE DIALYSIS CLINIC FOR THE H.O.P.E. STUDY. WE'RE HOPING TO DO MORE DENTAL PAIN. ENCOURAGED AT EVERY OPPORTUNITY AND SHOULD BE DOING THAT. THAT'S HOW MOST OF US RUN INTO SERIOUS PAIN ISSUES. NEXT SLIDE. I STILL REMEMBER AS A KID GOING TO THE DENTIST AND WAS NOT GOOD FOR ME BECAUSE I AVOIDED DENTISTS THEREAFTER. AND NOW THE MOST VEXING PROBLEM THEN IS BEING ATTACKED BY THESE "HEAL" TRIALS INTEGRATED MANAGEMENT OF CHRONIC PAIN OPIOID OVERUSE DISORDER. SO WE HAVE, YOU KNOW, 2 MILLION PEOPLE ARE OPIOID OVERUSE DISORDER, 40 TO 60% HAVE CHRONIC PAIN. THIS IS SOMETHING THAT THE PHYSICIANS, PRIMARY CARE PHYSICIANS, REALLY TRY AND STAY AWAY FROM AND UNFORTUNATELY THESE PEOPLE ARE POORLY SERVED. IT PROBABLY MAKES THEIR -- DEFINITELY MAKES THEIR PAIN WORSE, PROBABLY ALSO LEADS TO WORSE OPIOID OVERUSE DISORDER, LESS CHANCE OF GETTING INTO AND GETTING A RECOVERY, GOOD RECOVERY STATUS. BUT WE HAVE A NUMBER OF POPULATIONS THAT WE'RE LOOKING AT IN THIS SPACE. MAT IS MEDICATION-ASSISTED THERAPY. AND THE INTERVENTIONS SEEN HERE. AGAIN, THEY SPAN MEDICAL, BUT ALSO COMBINING WITH SELF-MANAGEMENT, PAIN SELF-MANAGEMENT, MINDFULNESS AND EXERCISE, FOR INSTANCE. AND THE SETTINGS SEEN HERE GOING TO BE A PLACE WHERE THESE FOLKS ARE POTENTIALLY RECRUITABLE, PRIMARY CARE, AND THE V.A. AND SOMETIMES HOSPITAL SETTINGS AS WELL. NEXT SLIDE. TRYING TO ADVANCE HEALTH EQUITY IN THE PAIN SPACE, I THINK WE HAVE TO THINK ABOUT THIS AS A SYSTEMIC ISSUE THAT HAS DIFFERENT FACTORS, EACH OF WHICH HAVE TO BE INCORPORATED INTO ANY PLAN. SO THERE ARE INDIVIDUAL BIOSOCIAL FACTORS WHICH PROBABLY AFFECT HOW PEOPLE PERCEIVE PAIN AND HOW MUCH SUFFERING IS ASSOCIATED WITH DIFFERENT NATURAL STIMULI, PROBABLY CULTURAL VARIATIONS NOT ONLY WHAT PEOPLE EXPERIENCE, REALLY HARD TO UNDERSTAND, BUT MAYBE MORE SO IN HOW PEOPLE COMMUNICATE WHAT THEY ARE EXPERIENCING. THIS CAN CERTAINLY LEAD TO REAL HEALTH INEQUITIES IF PEOPLE -- IF THE PERSON IN FRONT OF YOU IS NOT QUESTIONED TO GET AT THE BASIS OF WHAT DEGREE OF SUFFERING THEY ARE HAVING. INTERPERSONAL PATIENT-PROVIDER INTERACTIONS ARE IMPORTANT, SUCCESS RELIES ON TRUST OF PROVIDER AND PATIENT, HOW TO BUILD TRUST, PARTICULARLY WHEN THE WORKFORCE DOESN'T LOOK LIKE THE PERSON WHO IS TRYING TO COME TREATMENT OF PAIN.MS OF THE%- AND SO HOW TO WORK THIS SO WE GET THE BEST OUTCOMES IS REALLY IMPORTANT. THEN THERE ARE COMMUNITY AND SOCIOECONOMIC FACTORS IN A HAVE TO BE TAKEN INTO ACCOUNT, SOME OF THESE ARE, YOU KNOW, ACCESS TO THERAPY. IF YOU CAN'T TAKE OFF FROM WORK TO GET TO THE CLINIC OR YOU DON'T HAVE THE FUNDING TO GET THE TRANSPORTATION, AGAIN, THESE ARE THINGS THAT YOU DON'T THINK ABOUT THEM, THEY CAN REALLY AFFECT THE RESEARCH OUTCOME AND ALSO AFFECT THE POPULUS THAT YOU'RE ACTUALLY RELEVANT TO. AND WE HAVE TO WORK WITHIN THE SYSTEMS THAT WE HAVE, BUT WE HAVE THE OPPORTUNITY AS THE NIH TO WORK WITH HEALTHCARE SYSTEMS TO GENERATE KIND OF BETTER WAYS OF DEALING WITH CHRONIC PAIN THAT BENEFITS THE PATIENTS AND BENEFITS THE HEALTHCARE SYSTEM. AGAIN, POPULATIONS THAT WE'RE TRYING TO ENGAGE IN OUR EFFORTS TO IMPROVE HEALTH EQUITY, AND THE PAIN CONDITIONS AND THE INTERVENTIONS THAT ARE BEING TESTED AND DIFFERENT SETTINGS AT WHICH THESE ARE OCCURRING, AND THEN, AGAIN, THESE TABLES WERE BUILT BY CLINICAL RESEARCH TEAMS WHO KNOW EXACTLY WHICH GRANT IS TESTING WHAT AND WHAT SETTING AND FOR WHAT POPULATION. NOW, I MENTIONED EARLIER THAT THE WORKFORCE, PARTICULARLY IN THE CLINICAL PAIN SPACE, NEEDS TO BE STRENGTHENED GREATLY. AS I MENTIONED EARLIER, THERE'S BEEN EXPLOSION IN THE NEUROSCIENCE OF PAIN. LARRY TALKED TO YOU ABOUT, YOU KNOW, THIS NEW STUDY THAT JUST CAME OUT WHERE YOU CAN ACTUALLY SEE SIGNATURES IN THE OSCILLATORY PATTERNS, ELECTRICAL ACTIVITY IN CERTAIN PARTS OF THE BRAIN. NOT ONLY THAT, YOU CAN STIMULATE REGIONS TO CHANGE THAT OSCILLATORY ACTIVITY AND IMPROVE THE PERCEPTION OF PAIN. THIS WAS, YOU KNOW, AS WAS MENTIONED A VERY SMALL GROUP, PEOPLE WHO HAD PAIN DUE TO DAMAGE TO THEIR BRAIN, SO NEUROGENIC PAIN REALLY, BUT THIS IS WHAT -- THIS IS THE ORIGIN OF THE PAIN PERCEPTION THAT WE'RE FINALLY GETTING AT, AND TAKING THIS KIND OF KNOWLEDGE AND PUTTING IT TO PRACTICE TAKES REALLY SPECIALTY HIGH-EXPERIENCE PEOPLE AND NEED TO BUILD THAT. "HEAL" HAS A NUMBER OF PROGRAMS, I DON'T THINK THEY ARE EVEN ALL ON THIS LIST, K FELLOWSHIP PROGRAMS, ADMINISTRATIVE SUPPLEMENTS OF SUPPORT FOR CAREER ENHANCEMENT, MID-YEAR INVESTIGATOR AWARD, PATIENT-ORIENTED RESEARCH, A NEW K-12 PROGRAM RUN BY UNIVERSITY OF MICHIGAN, AND THEY RECRUIT PEOPLE AND THEY WILL MENTOR OVER THE YEARS AND DEVELOP THEIR CAREERS IN PAIN RESEARCH. AND AS LARRY MENTIONED, THIS ACROSS THE COUNTRY, COORDINATING ALL OUR TRAINING PROGRAMS UNDER THIS PURPOSE GROUP WHICH IS ACTUALLY A COMPANY THAT DOES EDUCATION, HEALTH EDUCATION, SO REAL PROFESSIONALS. I WAS HAPPY TO GO TO THE LAUNCH OF THEIR FIRST MEETING WHERE THEY BROUGHT IN TRAINEES AND MENTORS FROM ALL OVER THE COUNTRY IN THE HEAL INITIATIVE AND DID A FANTASTIC JOB KIND OF CREATING THE IMPORTANT CONVERSATIONS AND DISCUSSIONS AND I THINK IT'S A REALLY UNIQUE BUT REALLY POWERFUL PROGRAM THAT "HEAL" IS PILOTING HERE. NEXT SLIDE. AND, YES, WE MENTIONED ALREADY THAT IN THE PAIN SPACE WE ARE ATTEMPTING TO REDUCE THE SUFFERING THAT'S RELATED TO THIS ACTIVATION OF THE NOCICEPTIVE SYSTEMS, WHICH THEN CHANGE WITH CHRONIC PAIN OVER TIME. AND SO PAIN IS BY DEFINITION A VERY SUBJECTIVE EXPERIENCE, AND TO UNDERSTAND HOW WE MOVE FORWARD WE REALLY NEED TO BE LISTENING TO THE PEOPLE WHO ARE ACTUALLY THE PARTICIPANTS IN THE RESEARCH, AND PEOPLE WITH LIVED EXPERIENCE, AND WE HAVE A GREAT "HEAL" COMMUNITY PARTNERSHIP COMMITTEE THAT IS GIVING I THINK REALLY AMAZING INPUT ON KEY ISSUES, NOT ONLY FOR THOSE AFFECTED BY PAIN BUT ALSO SUBSTANCE ABUSE AND CLEARLY THERE'S THAT INTERACTION BETWEEN THESE TWO ISSUES. AND THEY HELPED US TO IDENTIFY, REFINE, PRIORITIZE ENGAGEMENT ACTIVITIES IN THE "HEAL" PROGRAMS. WHEN I LOOK ACROSS WHAT WE DO AT NINDS, "HEAL" IS REALLY THE ROLE MODEL RIGHT NOW FOR COMMUNITY ENGAGEMENT. WE'RE TRYING TO TAKE THIS WORK PACKAGE AND EXPORT IT TO A LOT OF THINGS THAT WE DO AT NINDS, BECAUSE WE THINK IT'S SO IMPORTANT. AND WE ALSO MAKE SUPPLEMENTS TO THE PROGRAM. YOU CAN'T ASK PEOPLE TO DO THIS JUST ON ALTRUISM. WE NEED TO PAY PEOPLE WITH LIVED EXPERIENCE THAT TAKE PART IN THE RESEARCH LIKE WE WOULD PAY ANYBODY ELSE IN THE RESEARCH PROGRAM. THEIR INPUT IS NO LESS VALUABLE THAN ANYONE ELSE'S, AND SO THESE SUPPLEMENTS ARE I THINK IMPORTANT IN BUILDING COMMUNITY PARTICIPATION INTO THE "HEAL" PROGRAM. NEXT SLIDE. AND JUST TO SAY THAT THE HOPE TRIAL IS COMPLETING ITS RECRUITMENT, 643, IN 2023, A HIGHLY ENGAGED PATIENT POPULATION. WE TALK ABOUT PATIENT ENGAGEMENT, "HEAL" IS A MODEL FOR NINDS, THE HOPE PROJECT WAS A MODEL FOR "HEAL." SO WE REALLY LEARNED A LOT BY WORKING WITH THE FOLKS IN THE HOPE PROJECT. NEXT SLIDE. ALSO, THE PRESCRIPTION AFTER CASAREAN TRIAL, WOMEN ARE PRESCRIBED AFTER C-SECTIONS, 20 TABLETS, 15 TABLETS, AND THE IDEA IS TO SHOW AND THEY SHOWED ONE WEEK POST-DISCHARGE. AND THERE WAS NO DIFFERENCE IN FULFILLING REFILLS. THE RESOLVE STUDY WHICH I THINK IS LINDA, IF I'M NOT MISTAKEN, MULTI-CENTER TRIAL FROM KAISER WASHINGTON, NORTHWEST, AND GEORGIA, AND ESENTIA HEALTH, TELEPHONE AND VIDEO CONFERENCE SO COULD WORK DURING COVID, A WEB PROGRAM, PAIN TRAINER, 3-ARM PARALLEL INTERVENTION DESIGN, COMPLETE ENROLLMENT OF 2231 PATIENTS, MANY RURAL AND OLDER ADULTS, 30% REDUCTION OVERALL PAIN SCORE. SO HOPEFULLY THESE KIND OF THINGS CAN THEN -- THEY ARE IN THE KAISER SYSTEM, HOPEFULLY THE HEALTHCARE SYSTEM CAN ADAPT THESE PROGRAMS WHEN WE SHOW THEM TO BE SUCCESSFUL. NEXT SLIDE. AND WITH THAT I WANT TO CONCLUDE AND CAN'T CONCLUDE WITHOUT THANKING ALL THE PEOPLE WHO DID SO MUCH WORK TO BUILD THE HEAL INITIATIVE, BOTH IN THE OFFICE OF THE DIRECTOR, MULTIPLE DIFFERENT INSTITUTES, DIFFERENT I.C. DIRECTORS, SUCH A VIBRANT PROGRAM, AND IT'S BEEN JUST A JOY TO BE PART OF IT. THANK YOU. >> THANK YOU FOR THE BROAD AND DEEP OVERVIEW. DO WE HAVE DR. CRISWELL? >> YES, I'M HERE. CAN YOU HEAR ME? >>I'M GOING TO JUST POINT OUT WE'RE A LITTLE BIT OVER TIME RIGHT NOW. AND SO PLEASE KEEP THAT IN MIND AS YOU GIVE US THIS MUCH-AWAITED UPDATE ON THE BACK PAIN CONSORTIUM RESEARCH PROGRAM, WHAT WE CALL BACPAC. ONE OF THE MORE FOCUSED PAIN MANAGEMENT RESEARCH EFFORTS BUT HIGHLY COLLABORATIVE AND INTERDISCIPLINARY EFFORTS UNDERWAY LED BY NIAMS. >> THANKS FOR THE OPPORTUNITY TO PROVIDE THIS UPDATE. "HEAL" IS CONCERNED NOT ONLY WITH OPIOID ADDICTION BUT CAUSES OF OPIOID ADDICTION, CERTAINLY CHRONIC PAIN IS A COMMON CAUSE OF OPIOID ADDICTION, AS YOU HEARD ALREADY BACK PAIN IS A VERY COMMON CAUSE OF ACUTE AND CHRONIC PAIN. SO HENCE THE FOCUS OF THE PROGRAM. NEXT SLIDE. SO, THE BACK PAIN CONSORTIUM, BACPAC, AIMS TO PROVIDE TREATMENT FOR INDIVIDUALS THROUGH DISCOVERING MECHANISMS OF CHRONIC LOW BACK PAIN AND IDENTIFYING AND TESTING NEW INTERVENTIONS TARGETED TO INDIVIDUAL PATIENTS, A REALLY IMPORTANT FEATURE. SO, ON THE NEXT SLIDE, BACPAC IS A PATIENT CENTERED RESEARCH PROGRAM, AT THE BASIC RESEARCH LEVEL BACPAC WILL DEVELOP AN INTEGRATED THEORETICAL MODEL OF CHRONIC LOW BACK PAIN BASED ON IMPROVED UNDERSTANDING OF MECHANISMS AND CLINICAL TRIALS AND MULTI-MODAL, CREATING CLINICAL COHORTS WITH VERY DEEP PHENOTYPING INCLUDING PATIENT-REPORTED OUTCOMES, AND AT THE CLINICAL LEVEL BACPAC AIMS TO CREATE ALGORITHMS TO MATCH EACH PATIENT TO THE BEST TREATMENTS BASED ON THEIR PHENOTYPE AND THEIR PSYCHOSOCIAL CONTEXT. SO, NEXT SLIDE. SO, TO ADDRESS THESE VARIOUS ELEMENTS BACPAC INCLUDES SEVERAL COMPONENTS, THREE RESEARCH CENTERS, EACH RUN THEIR OWN STUDIES, COLLECT BIOLOGICAL, MECHANICAL, PSYCHOSOCIAL, AND OTHER DATA FROM PATIENTS TO IDENTIFY DIFFERENT PHENOTYPES, AND HENCE POSSIBLE MARKERS OF TREATMENT RESPONSE. THE TECHNOLOGY RESEARCH SITES CREATE, TEST, AND DISTRIBUTE TECHNOLOGY AND METHODS TO TEST AND QUANTIFY AND RELIEVE CHRONIC LOW BACK PAIN. AND THEN THERE ARE THREE PHASE 2 CLINICAL TRIALS ADDRESSING DIFFERENT INTERVENTIONS. IMPORTANTLY THERE'S A DATA INTEGRATION ALGORITHM DEVELOPMENT AND OPERATION CENTER THAT PLAYS A CRUCIAL ROLE TO COORDINATE AND HARMONIZE DATA AND CONSORTIUM ACTIVITIES. I'M GOING TO VERY BRIEFLY TOUCH UPON THESE COMPONENTS IN THE NEXT FEW SLIDES, IF YOU CAN GO ON. SO FIRST THE MECHANISTIC RESEARCH CENTERS, REACH MRC EXAMINING BIOSOCIAL, RELIES UPON TWO OBSERVATIONAL COHORTS, AS SHOWN ON THE SLIDE, AND THE HEALING LB3P IS COLLECTING DATA WITH OVER 750 ENROLLEES TO DATE, AND THEN THE THIRD MECHANIC MEC CENTER IS RUNNING WITH A SMART DESIGN TO IDENTIFIED PREDICTING RESPONSES TO FOUR INTERVENTIONS, MINDFULNESS, PHYSICAL THERAPY, ACUPRESSURE AND DULOXETINE, WITH A SIGNIFICANT AMOUNT OF WORK BEFORE THE STUDIES BEGAN. FOR EXAMPLE ALL THE DATA COLLECTION APPROACHES WERE STANDARDIZED AND HARMONIZED ENSURING VERY RICH DATASETS THAT CAN BE ACCESSED AND INTEGRATED ACROSS EFFORTS. SO ON THE NEXT SLIDE, THIS HIGHLIGHTS THE EXCITING TECHNOLOGY DEVELOPMENT SITES, THERE ARE SEVEN OF THESE. I WON'T GO THROUGH ALL BUT STARTING AT THE LOWER LEFT YOU'LL SEE THAT THESE DEVELOP ROBOTIC APPAREL, DIGITAL PLATFORM EFFORTS, MEASURING END PLATE PATHOLOGY, MEASURING DENSITY IN THE BRAIN, USE OF NANOCOMPOSITE SENSORS IN ADDITION LASTLY TO USE OF FOCUSED ULTRASOUND, EXCITING TECHNOLOGIES THAT ARE BEING STUDIED, AND SOME OF THESE RESULTS HAVE BEEN PUBLISHED SUCH AS IMPROVEMENTS IN THE TECHNOLOGY AROUND SPINE MRIs. SO IF YOU GO TO THE NEXT SLIDE, THE THIRD COMPONENT IS THE THREE PHASE 2 CLINICAL TRIALS, DEPICTED ON THE SLIDE EXAMINING VIRTUAL REALITY PROTOCOLS TO MANAGE BACK PAIN, EXPLORING COMBINATION OF ANTIDEPRESSANTS AND ENHANCED FEAR AVOIDANCE REHABILITATION PROTOCOL FOR PATIENTS WITH LOW BACK PAIN AND DEPRESSION OR ANXIETY, AND A TRIAL BY FRITZ AND COLLEAGUES THAT LOOKS FOR WHETHER A COMPREHENSIVE PROGRAM TO IMPROVE THE PATIENT'S ABILITY AND CONFIDENCE IN MANAGING THEIR OWN PAIN BEFORE SURGERY CAN REDUCE RISK OF POST-SURGICAL OPIOID USE. NEXT SLIDE JUST ILLUSTRATES THE THREE VIRTUAL REALITY PROTOCOLS FOR THAT FIRST TRIAL THAT I MENTIONED, ONE BEING SHAM INTERVENTION, ANOTHER BEING AN IMMERSIVE DISTRACTIVE INTERVENTION AND THEN THE THIRD IS IMMERSIVE SKILLS-BASED VIRTUAL REALITY PROTOCOL. WE'RE REALLY EXCITED ABOUT ALL OF THESE EFFORTS. ON THE NEXT SLIDE, COLLABORATION IS VERY IMPORTANT AT "HEAL," AND IMPORTANT IN BACPAC, AIMING TO CAPITALIZE ON DATA AND BRAINPOWER ACROSS THE CONSORTIUM TO ENABLE NEW PARADIGMS IN THE TREATMENT OF CHRONIC LOW BACK PAIN, THIS INCLUDES OF COURSE HARMONIZING DATA COLLECTION AS I'VE MENTIONED, CREATING THEORETICAL MODEL OF CHRONIC LOW BACK PAIN AND ALSO LAUNCHING A COLLABORATIVE MULTI-SITE CLINICAL TRIAL CALLED THE BEST TRIAL, WHICH I'LL ALSO DESCRIBE IN JUST A MINUTE. BUT TO ENSURE HARMONIZATION OF THE DATA COLLECTION MEASURES AND PROTOCOLS, WORKING GROUPS WERE CREATED TO STANDARDIZE BIOBEHAVIORAL, BIOMECHANICAL, BIOSPECIMEN AND IMAGING AND DATA COLLECTION IN BACPAC, MADE PUBLICLY AVAILABLE. I MENTIONED THIS THEORETICAL MODEL, AN IMPORTANT ASPECT OF THE EFFORTS, SHOWN ON THE NEXT SLIDE. THE BACPAC INVESTIGATORS ESTABLISHED THIS FOR PHENOTYPES, INTERVENTIONS, EXPLANATORY THEORIES, MACHINE LEARNING, ET CETERA. THE MODEL AIMS TO INTEGRATE FACTORS INTERNAL AND EXTERNAL, THAT AFFECT PAIN PROCESSING. THIS INCLUDES MECHANISMS IN THE LOWER BACK, THAT'S REPRESENTED IN THE BOTTOM CIRCLE, DORSAL HORN AND SPINAL CORD, REPRESENTED IN THE MIDDLE CIRCLE, AND THEN THE BRAIN CAPTURED IN THE UPPER CIRCLE. SO THESE ALL CONTRIBUTE TO AN INDIVIDUAL'S EXPERIENCE OF PAIN, AND THIS EXPERIENCE CAN BE INDIRECTLY ASSESSED USING VARIOUS MEASURES OF PAIN AND DISABILITY. SO THE MODEL WAS DERIVED BY INTEGRATING EXPERT OPINIONS ON THE RISK AND PROGNOSTIC FACTORS WITH RESULTS OF EXTENSIVE LITERATURE REVIEW WHICH ASSESSED OVERALL STRENGTH OF EVIDENCE FOR IDENTIFIED RISK FACTORS AND OF COURSE OVER THE COURSE OF THIS PROGRAM THE MODEL WILL BE REFINED BASED ON BACPAC DATA AND OTHER DATA TO REFLECT A STATE-OF-THE-ART MODEL FOR CHRONIC LOW BACK PAIN. AND AS THE SLIDE INDICATES, THE MODEL AND PROCESS TO DEVELOP WERE RECENTLY PUBLISHED. SO IF YOU GO TO THE NEXT SLIDE. I MENTIONED ANOTHER FEATURE OF THIS PROGRAM THAT WE'RE EXCITED ABOUT WHICH IS THE BEST TRIAL, THE BIOMARKERS FOR EVALUATING SPINE TREATMENTS, A FOUR-ARM SMART TRIAL, DESIGNED TO ESTIMATE AN ALGORITHM, ASSIGN SEQUENCE OF TWO TREATMENTS FOR CHRONIC LOW BACK PAIN, BASED ON A PATIENT'S PHENOTYPIC MARKERS SO THE TRIAL IS EXPLORING FOUR INTERVENTIONS THAT HAVE BEEN SHOWN TO HAVE SOME EFFECTIVENESS FOR CHRONIC LOW BACK PAIN PATIENTS. THIS INCLUDES ENHANCED SELF-CARE, ACCEPTANCE AND COMMITMENT THERAPY, EVIDENCE BASED EXERCISE AND MANUAL THERAPY, AND THEN DULOXETINE. IMPORTANTLY THE TRIAL IS POWERED TO IDENTIFY WHICH TREATMENT WILL BE BEST FOR WHICH SUBGROUP OF PATIENTS, INSTEAD OF FOCUSING ON AVERAGE EFFECTS ON A GROUP OF PATIENTS. NEXT SLIDE, WHICH I WON'T GO OVER IN DETAIL, SHOWS THE PROTOCOL. THERE ARE TWO TREATMENT PERIODS, ALL PARTICIPANTS ARE RANDOMIZED TO ONE OF THE FOUR IN THE FIRST PERIOD, TREATMENT IN SECOND PERIOD DEPENDS ON INITIAL RESPONSE TO FIRST TREATMENT. PARTICIPANTS ARE PHENOTYPED AT THREE TIME POINTS, IMPORTANT GIVEN THE GOALS, BEFORE EACH OF THE TWO TREATMENT PERIODS, DURING THE FOLLOW-UP. ALL PARTICIPANTS UNDERGO LIGHT PHENOTYPING BASIC BIOMECHANICS, CLINICAL SPINE MRI FINDINGS, X-RAY IMAGES, AND A SUBSET ALSO UNDERGO DEEP PHENOTYPING ADVANCED BIOMECHANICS, ADVANCED MRI, BRAIN MRI, QUANTITATIVE SENSORY TESTING RESULTS. NEXT SLIDE. THIS SHOWS THE TIMELINE. THE TRIAL WAS LAUNCHED LAST SEPTEMBER. WE ANTICIPATE ENROLLMENT TO END IN SEPTEMBER OF THIS YEAR ALLOW THE TRIAL TO COMPLETE IN SEPTEMBER OF 2024. AND LASTLY, THINKING ABOUT THE WHOLE SYSTEM, AS YOU'VE HEARD, MOVING FORWARD, NEXT SLIDE, SORRY, WE AIM TO BUILD ON BACPAC AS WELL AS OTHER "HEAL" PROGRAMS SUCH AS REJOIN THAT SOME OF YOU MAY HAVE HEARD ABOUT TO DEVELOP A WHOLE JOINT PERSPECTIVE. SO, WE RECOGNIZE THE NEED TO INTEGRATE INFORMATION ACROSS ALL DOMAINS, MANY ARE DEPICTED HERE, ENVIRONMENT, BEHAVIOR, MECHANICS, AS WELL AS TISSUE, CELLULAR, MOLECULAR PROCESSES, TO MAINTAIN HEALTH, PREVENT OR ADDRESS PAIN AND PREVENT ADDICTION. SO, THIS WILL BEGIN BY INTEGRATING INFORMATION FROM THE VARIOUS "HEAL" PROGRAMS, I'VE TALKED ABOUT BACPAC THIS MORNING BUT WE ALSO HOPE TO LEARN ABOUT KNEE AND TMJ INNERVATION TO REJOIN, APPLY TO BACK PAIN AND OTHER JOINT PAIN, BUILD ON BIOMARKERS THAT YOU ALSO HEARD ABOUT TO DEVELOP BIOMARKERS FOR PAIN IN OTHER JOINTS, EXPLORING HOW CELLULAR MOLECULAR AND GENETIC INFORMATION FROM THE PRO SITUATION PROGRAM WILL INFORM DEVELOPMENT OF BIOMARKERS FOR OTHER TYPES OF PAIN AND EXAMINE WAYS TO SHARE CLINICAL DATA, TISSUES, AND OTHER RESOURCES ACROSS PROGRAMS TO BETTER LEVERAGE RESEARCH OPPORTUNITIES. MY LAST SLIDE, WHICH IS MOSTLY BLANK BUT REPRESENTS MANY, MANY, MANY PEOPLE, I WANT TO THANK THE RESEARCHERS PARTICIPATING IN BACPAC, BACPAC STAKEHOLDERS AND BOARD MEMBERS, I CERTAINLY WANT TO ACKNOWLEDGE THE NIH PROGRAM STAFF WHO MANAGE THIS COMPLEX -- THESE COMPLEX AWARDS, INCLUDING LESLIE AND ERIN, CHUCK, TED, AND MANY OTHER PROJECT SCIENTISTS AND PROJECT COORDINATORS FROM MULTIPLE INSTITUTES, CENTERS, OFFICES, AND OF COURSE ACKNOWLEDGE THE PATIENTS WITHOUT WHOM WISH THIS WOULDN'T BE POSSIBLE. OUR HOPE IS DEVELOP CLEAR GUIDELINES TO INDIVIDUALIZE TREATMENT FOR CHRONIC LOW BACK PAIN. BACK TO YOU, DR. BAKER. >> THANK YOU, DR. CRISWELL. I WOULD LIKE TO MAKE SURE WE HAVE TIME FOR DISCUSSION. I'LL GO THROUGH MY SLIDES NOW QUICKLY AND THOSE OF YOU WHO HAVE QUESTIONS FOR DR. KOROSHETZ OR CRISWELL PLEASE SAVE THEM FOR THE GENERAL DISCUSSION THAT WILL FOLLOW MY BRIEF TALK NOW. YOU HAVE HEARD A LOT ABOUT SPECIFIC PROGRAMS AND PROJECTS WITHIN "HEAL." I'LL NOW TAKE A STEP OR TWO BACK AND JUST REMIND YOU IN THE NEXT SLIDE OF WHAT THE OVERARCHING VISION IS FOR THIS, HELPING TO END ADDICTION LONG-TERM INITIATIVE TO COMBINE SCIENCE, EFFORTS OF SCIENTISTS AND RESEARCH COMMUNITY TO THE STRENGTHS AND POWER OF THE COMMUNITIES IN WHICH OUR PATIENTS AND STAKEHOLDERS LIVE TO PROVIDE SCIENTIFIC SOLUTIONS AND HELP END ADDICTION LONG TERM. THIS MISSION INCLUDES EFFORTS TO ACCELERATE DEVELOPMENT OF NEW TREATMENTS, SAFE, NON-ADDICTIVE STRATEGIES TO PREVENT AND TREAT PAIN, OPIOID MISUSE, ADDICTION, TO REVERSE OVERDOSE. IN THE NEXT SLIDE I SHOW JUST -- DR. TABAK MENTIONED THESE SO I'LL BE QUICK, BUT CHRONIC PAIN IS NOT GOING AWAY. IT AFFECTS SO MANY MILLIONS OF AMERICANS, HAS INCREDIBLE BURDEN OF DISEASE AND REALLY AFFECTS QUALITY OF LIFE FOR MANY PEOPLE AND MANY PEOPLE WITH OTHER HEALTH CONDITIONS. AND A PARALLEL TRACK, WE HAVE RECORD NUMBERS OF DRUG OVERDOSES AFFECTING FAMILIES, COMMUNITIES, INDIVIDUALS ACROSS THE COUNTRY, DRIVEN BY THE INCREASING ACCESSIBILITY OF FENTANYL AND CONTAMINATION OF FENTANYL AND DIFFERENT DRUGS, BUT ALSO A LACK OF INFRASTRUCTURE AND COMMUNITY SUPPORT FOR SOME OF THE EFFECTIVE INTERVENTIONS THAT WE HAVE. AND THEN LASTLY WE HAVE OUR BIOPHARMACEUTICAL PARTNERS WHO HAVE INTERESTING, INNOVATIVE APPROACHES AND ABILITY TO COMMERCIALIZE THESE TO PROVIDE THESE NEW TREATMENTS, AND YET WE'RE NOT SEEING INVESTMENTS AND PROGRESS OF MANY OF THE PROGRAMS THAT WE'RE AWARE OF AND THAT COULD BE SCIENTIFIC SOLUTIONS WE'RE SEEKING FOR PEOPLE WITH PAIN AND ADDICTION. SO THIS IS OUR LANDSCAPE. AND NEXT SLIDE, I BEGIN TO TALK ABOUT SOME OF THE WAYS "HEAL" RESEARCH IS MEETING THIS CHALLENGE. THE FIRST EXAMPLE, NEXT SLIDE, IS THE STUDY, YOU WILL RECALL THE GROUP OF NEONATOLOGISTS AND NURSES WHO CONTRIBUTED TO THIS STUDY LED BY THE ECHO PROGRAM WITH NICHD, NATIONAL INSTITUTE ON CHILD HEALTH. WE HAVE INFANTS BORN EXPOSED TO OPIOIDS, UNDERGOING WITHDRAWAL IN THE NICU, RESEARCH UNDERWAY TO UNDERSTAND THE BEST WAY OF EVALUATING THEIR LONG-TERM DEVELOPMENT BUT IN THE SHORT TERM WAYS TO ADDRESS WITHDRAWAL SYSTEMS; THE EAT, SLEEP, CONSOLE APPROACH, WHETHER THEY ARE ABLE TO EAT, SLEEP, BE CONSOLED WAS TESTED, RANDOMIZED CLINICAL TRIAL FOUND TO REDUCE TIME IN THE HOSPITAL AND REDUCE AMOUNT OF OPIOID MEDICATIONS NEEDED TO ADDRESS THOSE WITHDRAWAL SYMPTOMS. NEXT SLIDE. FINDINGS THAT DR. KOROSHETZ MENTIONED, I WON'T LINGER ON, BUT THERE ARE BEGINNING TO BE STUDIES THAT CAN IMAGE THE BRAIN AND UNDERSTAND THE CHRONIC PAIN SIGNATURES THAT ARE DIFFERENT AMONG INDIVIDUALS, IN THIS CASE PAIN CAUSED BY STROKE OR AMPUTATION, AND THESE PATIENT-SPECIFIC SIGNALS CAN GIVE A PROMISE TO OUR COMMUNITY IN TERMS OF WHAT WE COULD BEGIN TO ADDRESS, HOW WE COULD BEGIN TO PERSONALIZE THE TREATMENT FOR PEOPLE WITH CHRONIC PAIN. NEXT SLIDE PLEASE. WE ALSO HAVE -- DR. D'ONOFRIO IS ONE OF THE LEADS FOR THIS TRIAL, OR THE LEAD, THRUST WITHIN HEAL, BUPRENORPHINE FOR TREATMENT OF OPIOID USE DISORDER, IN THE EMERGENCY DEPARTMENT, HOPEFULLY RESULTING IN GREATER ACCESS AND USE OF THE LIFE-SAVING MEDICATIONS FOR TREATMENT OF OPIOID USE DISORDER THAT WE HAVE, WE KNOW WORK, AND WAYS TO INTEGRATE INTO CLINICAL CARE. SO, SIGNS OF PROGRESS TO ADDRESS THE REALLY SIGNIFICANT CHALLENGES WE'RE FACING AS A COUNTRY IN OUR PAIN AND ADDICTION CRISES. NEXT SLIDE PLEASE. A REMINDER OF WHAT WE'RE SEEKING TO DO. THIS KIND OF IS INTENDED TO PROVIDE INTRODUCTION TO SOME OF THE RESEARCH PROGRAMS YOU'LL HEAR ABOUT IN THE SECOND HALF F THE MEETING, STRATEGIES TO REDUCE RISK OF ADDICTION AND INTEGRATE EFFECTIVE AND SUSTAINABLE PREVENTION AND TREATMENT STRATEGIES, INCLUDING IMPLEMENTING INTO COMMUNITY AND SUSTAINABLE FRAMEWORKS THAT CAN BE TAKEN UP AND USED TO SAVE LIVES. RESEARCH TO SUPPORT HEALTHY DEVELOPMENTAL PATHS FOR BABIES EXPOSED TO OPIOIDS USING UNDERSTANDING HOW A MOTHER'S SUBSTANCE USE CAN CONTRIBUTE TO THEIR LONG-TERM HEALTH AND NEW THERAPEUTICS FOR THE CYCLE, WITHDRAWAL, OPIOID USE DISORDER, AND OVERDOSE. NEXT SLIDE PLEASE. PLEASE GO TO OUR WEBSITE, YOU'LL SEE A LOT MORE INFORMATION ABOUT THE RESEARCH FINDINGS THAT ARE COMING THROUGH, AND ALSO THE WAYS THAT WE'RE SEEKING TO BUILD THE RESEARCH COMMUNITY TO BETTER PREPARE FOR THESE CRISES AS THEY CONTINUE TO EVOLVE. NEXT SLIDE PLEASE. A LITTLE BIT OF WHERE WE ARE NOW IS IN THE FOLLOWING SLIDE. WE HAVE AN ANNUAL REPORT THAT DETAILS A LOT MORE PROGRESS AND UPDATES ON THE RESEARCH THAT WE HAVE LAUNCHED SINCE YOU STARTED WORKING WITH US, DEVELOPING AND BUILDING THE HEAL INITIATIVE, INCLUDING SOME OF THE SCREENING PLATFORMS, DECISION TOOLS, COMMUNITY-BASED APPROACHES TO HELP END ADDICTION LONG TERM AS WELL AS SOME WAYS WE'RE LEVERAGING OUR DATA ECOSYSTEM, I HOLD YOU ABOUT THOSE IN THE PAST, AND CONTINUING TO BUILD CONNECTIONS WITH THE USERS AND PRACTITIONERS WHO ARE GOING TO TAKE RESEARCH FINDINGS AND TURN THEM INTO SOLUTIONS FOR PEOPLE WITH PAIN AND ADDICTION. NEXT SLIDE PLEASE. WE CONVENED THE "HEAL" INVESTIGATORS COMMUNITY, THERE WERE OVER 600 PEOPLE THERE, VIRTUAL AND IN PERSON, FOCUS ON EARLY STAGE INVESTIGATORS AND SOME OF THE EXCITING AREAS OF SCIENCE THAT ARE COMING THROUGH. SO THANK YOU FOR THOSE WHO TOOK PART AND TUNED IN. NEXT SLIDE PLEASE. AND WHERE ARE WE NOW? WITH OVER $2.5 BILLION DIRECTED TOWARDS RESEARCH IN PAIN AND ADDICTION, OVER 1,000 PROJECTS, ALL 50 STATES, YOU HEARD ABOUT OVER 300 CLINICAL TRIALS THAT WE HAVE UNDERWAY, INCLUDING OVER 100 PROJECTS ADDRESSING BACK PAIN, THIS HAS LED TO OVER 40 FDA APPROVALS FOR INVESTIGATIONAL NEW DRUGS AND DEVICES. THESE ARE IND SUBMISSIONS TO THE FDA THAT SEEK TO BRING FORWARD THOSE INNOVATIONS TO PRODUCTS THAT CAN BE USED BY PATIENTS, AND OF COURSE ACTIVE ONGOING PARTNERSHIPS WITH FEDERAL AGENCIES AND OUR PARTNERS IN PRIVATE SECTOR, ACADEMIA, AND COMMUNITIES. NEXT SLIDE PLEASE. HERE IS WHERE OUR FUNDING GOES IN TERMS OF BREAKDOWN INTO DIFFERENT AREAS OF RESEARCH FOCUS. YOU'LL SEE OVER TIME AN EXPANSION OF THE PRE-CLINICAL AND TRANSLATIONAL RESEARCH IN PAIN MANAGEMENT. AND ONGOING EFFORTS IN ALL OF THE DIFFERENT DOMAINS OF THE HEAL INITIATIVE AS OUR BUDGET HAS GROWN OVER TIME. NEXT SLIDE PLEASE. AND SOME OF OUR ONGOING PRIORITIES THAT WE'VE DISCUSSED WITH THIS GROUP IN THE PAST, AND KEEP IN MIND FOR TODAY THE NEEDS TO SET THE RIGHT BALANCE FOR PAIN AND ADDICTION RESEARCH, RECOGNIZING THAT THERE'S A LOT OF OVERLAP BOTH OF THE MOLECULAR LEVEL AND AT THE POPULATION LEVEL. FOCUS ON CO-OCCURRING CONDITIONS BECAUSE NO ONE INTERVENTION IS GOING TO BE STRONG ENOUGH TO SOLVE EVERY HEALTH PROBLEM, AND SO WE HAVE TO BE LOOKING AT THE WHOLE PERSON AND CONSIDERING THAT IN OUR RESEARCH. RESEARCH FOCUSED ON STIGMA AND INEQUITIES IN OUR HEALTH CARE SYSTEM BEING REALISTIC IN THE RESEARCH WE CONDUCT SO WE BEGIN TO BREAK DOWN THOSE BARRIERS TO HIGH-QUALITY CARE FOR ALL, INTEGRATING VOICE OF LIVED EXPERIENCE IS A REALLY IMPORTANT TALL TOWARD THAT GOAL, BUT NOT THE ONLY ONE. WE'RE ALSO LEVERAGING THE POWER OF THE DATA COMING OUT OF OUR STUDIES, TO PROVIDE NEW LINES OF INQUIRY AND BETTER UNDERSTAND THE CONDITIONS WE'RE STUDYING, AND OF COURSE TRAINING THE NEXT GENERATION OF RESEARCHERS, YOU HEARD FROM DR. KOROSHETZ, IT'S A KEY TOOL FOR LONG TERM AND SUSTAINABLE INITIATIVE TO ADDRESS THESE CHALLENGES. NEXT SLIDE PLEASE. THIS IS OUR AGENDA. WE'RE OVER TIME, AS YOU'LL SEE. BUT I DO WANT TO MAKE SURE THAT WE HAVE A MOMENT FOR DISCUSSION, BOTH OF WHAT WE HEARD ABOUT FROM THE PREVIOUS SPEAKERS AND ALSO THE OVERVIEW I JUST PROVIDED. WE'LL MAKE A FEW TWEAKS TO THE AFTERNOON'S PROGRAM BUT THE KEY QUESTION WILL BE ASKING HOW DO THESE PROGRAMS FIT TOGETHER, HOW DO THE NEW RESEARCH PROJECTS THAT THE TEAMS HAVE COME TOGETHER TO PROPOSE AND ADVANCE THE OVERALL GOAL OF SCIENTIFIC SOLUTIONS TO HELP BRING ABOUT AN END TO THE OPIOID CRISIS, INCLUDING STRATEGIES, TREATING PAIN, ENHANCED OUTCOMES FOR INFANTS EXPOSED TO OPIOIDS DURING A MOTHER'S PREGNANCY. I'LL NOW PAUSE AND INVITE QUESTIONS FROM THE MULTI-DISCIPLINARY WORKING GROUP AND OTHERS ON THE CALL. THANK YOU VERY MUCH FOR YOUR ATTENTION. >> I'LL START. >> GO AHEAD. >> VERY AMBITIOUS PORTFOLIO, IT'S VERY EXCITING. THERE ARE -- I THINK THAT YOU'VE HIT ON ALL THE DIFFERENT AREAS, EVERYONE HAS, WALTER'S PRESENTATION, I THINK WE'RE LOOKING FORWARD TO SEEING RESULTS OF MORE OF THESE STUDIES. >> THANK YOU, GAIL. GO AHEAD, ERIC. >> THANKS. I'M VERY IMPRESSED BY THIS ENTIRE PORTFOLIO. I HAD A QUESTION ABOUT THE BACPAC INITIATIVE WITH RESPECT TO THE CLINICAL TRIALS. HOW ARE THE MECHANISTIC EFFORTS IN THE OTHER STAGES AND PHASES OF THE BACPAC PROGRAM BEING ROLLED INTO THESE CLINICAL TRIALS? ARE WE GOING TO BE USING THE METHODOLOGY -- IN PARTICULAR THE NEUROSCIENTIFIC METHODOLOGIES THAT ARE BEING PUSHED FORWARD IN THE EARLIER FOUNDATIONAL STAGES OF BACPAC INTO THESE CLINICAL TRIALS? >> YEAH, THANK YOU FOR THAT QUESTION. SO, I THINK YOU'RE TALKING IN PARTICULAR ABOUT THE TECHNOLOGY CENTERS THAT ARE IDENTIFYING AND TESTING NEW TECHNOLOGIES. WE HAVE TO UNDERSTAND FIRST THEIR EFFECTIVENESS, EFFICACY, BEFORE WE CAN INCORPORATE THEM INTO FUTURE WORK WHICH I THINK SPEAKS TO THE FACT THAT FOR US TO FULLY BENEFIT FROM WHAT WE'RE LEARNING IN THE FIRST PHASE WE'LL CONTINUE TO FOCUS ON TAKING TECHNOLOGIES AND APPLYING THEM IN FUTURE STUDIES. THAT I THINK IS PART OF THE REASON WE SPENT SO MUCH TIME FOCUSING ON THE INFRASTRUCTURE AND ESTABLISHING DATA COLLECTION METHODS, ET CETERA, SO THAT NOT ONLY ARE WE HARMONIZING EFFORTS IN THIS CURRENT PHASE BUT SO WE CAN FULLY LEVERAGE AND INTEGRATE FUTURE STUDIES WITH THE CURRENT DATA. SO, I HOPE THAT ADDRESSES TO SOME EXTENT YOUR QUESTION. WE FULLY INTEND TO CONTINUE WORK IN THIS AREA BUT AS I MENTIONED WE WANT TO MAKE SURE WE'RE ALSO LEVERAGING NOT ONLY WHAT WE'RE LEARNING THROUGH THE TECHNOLOGY AND MECHANIC MECHANISTIC CENTET REJOIN, MYOFASCIAL PAIN, THINKING ABOUT THE LANDSCAPE TO FORMULATE OUR PLANS MOVING FORWARD. >> THAT'S REALLY HELPFUL. I GUESS I'M HOPING THAT THE DEEP PHENOTYPING THAT'S HAPPENING AT MULTIPLE BIOPSYCHOSOCIAL LEVELS INCLUDING NEUROBIOLOGICAL LEVEL, I'M HOPING THAT WE'LL SEE SOME DEEP PHENOTYPING FOLLOWING THESE VARIOUS INTERVENTION PACKAGES AND TREATMENTS SO WE CAN SEE IF THE MULTIVARIATE SIGNATURE OF RESPONSIVENESS TO THIS INTERVENTION, IF IT CHANGES ACROSS THESE DEEP PHENOTYPES. I THINK THAT WOULD BE REALLY INTERESTING AND PUSH THE FIELD FORWARD. >> ABSOLUTELY. I THINK THIS THEORETICAL MODEL THAT I MENTIONED ACKNOWLEDGES OR RECOGNIZES THE FACT THERE ARE SO MANY DIMENSIONS TO THE PROBLEM, WHY IT'S SO DIFFICULT TO TACKLE. WITHOUT DATA WE CAN'T ANSWER QUESTIONS, SO I DEGREE IT'S IMPORTANT BUT THE INDIVIDUALIZATION, SO HOW THESE DIFFERENT PHENOTYPES CORRESPOND OR RELATE TO DIFFERENT SUBGROUPS OF PATIENTS IS GOING TO BE REALLY IMPORTANT AND INFORMATIVE SO WE CAN BE EFFICIENT MOVING FORWARD. >> THANK YOU. WONDERFUL PROGRAM. >> THANKS. >> THANK YOU, ERIC. OTHER QUESTIONS FOR THE GENERAL DISCUSSION IN THE OPEN SESSION OF TODAY'S MEETING? >> A SMALL COMMENT. IT WAS REALLY IMPRESSIVE. IT MIGHT BE WORTH TELLING THE PUBLIC THERE'S A BIG EFFORT NOW TO LOOK AT THE, IF YOU WILL, TRANSCRIPTOMES AND PROTEOMES IN HUMAN TISSUE WITH THE HOPE IT WILL SPEED UP DEVELOPMENT OF THERAPIES SPECIFICALLY DIRECTED AT HUMAN, CERTAINLY OBVIOUSLY I ENDORSE THE ANIMAL MODELS BUT AT SOME POINT WE'RE GOING TO TRANSLATE IT. >> THANK YOU. YEAH, WE'LL THINK ABOUT WAYS TO WORK TO COMMUNICATE THAT. I AGREE IT'S SOMETHING WE'VE BEEN WORKING ON IN "HEAL" AND EVERYONE KNOWS. OKAY. I THINK IF THERE ARE NO ADDITIONAL QUESTIONS WE CAN END THE OPEN SESSION OF TODAY'S HEALTH MULTI-DISCIPLINARY WORKING GROUP MEETING