>> WELCOME TO DAY TWO OF THE ADVISORY COMMITTEE TO THE DIRECTOR OF NIH MEETING. WE'VE HAD A LITTLE SHIFTING AROUND OF OUR MEMBER LOCATIONS. WE HAVE A FEW OF YOU ON SITE AND A FEW MORE TODAY ONLINE, BUT I THINK WE DEFINITELY STILL HAVE A QUORUM SO WE'RE GOING TO GO AHEAD AND GET STARTED. OUR FIRST PRESENTATION THIS MORNING WE'RE VERY EXCITED TO SEE IS GOING TO BE FROM DR. NORA VOLKOW AND DR. WALTER KOROSHETZ ABOUT HELPING TO END ADDICTION LONG TERM, THE HEAL INITIATIVE. AN UPDATE FROM HEAL. YOU'RE UP. >> GOOD MORNING, EVERYONE. I'M GOING TO NEED HELP TO SET UP THE SLIDES. BUT WHILE THEY SET THEM UP, I WANT TO FIRST OF ALL THANK EVERYBODY FOR YOUR WORK AND YOUR WILLINGNESS TO GIVE US ADVICE, AND ALSO INDICATE THAT IT'S AN HONOR FOR ME TO BE PRESENTING ALONGSIDE OF DR. WALTER KOROSHETZ IN ONE OF WHAT HAS BEEN THE BOLDEST INITIATIVES THAT WE'VE UNDERTAKEN TARGETED VERY MUCH TO ADDRESS THE OVERDOSE CRISIS. THE OVERDOSE CRISIS THAT REALLY STARTED AT THE LATE 1990s AND HAS ACTUALLY PROCEEDED EXPANDING THE NUMBER AND CONSEQUENCES FROM OVERDOSES AND DEATH LINKED PREDOMINANTLY WITH OPIOIDS IS THE RESULT OF TWO AREAS OF TREMENDOUS NEGLECT. ONE OF THEM, THE NEGLECT OF HEALTHCARE SYSTEMS TO ADDRESS SUBSTANCE USE AND SUBSTANCE USE DISORDERS, AND THE OTHER ONE, THE NEGLECT THAT WE HAVE HAD IN ADDRESSING THE NEED OF PATIENTS SUFFERING FROM PAIN. THE DEVASTATING CONSEQUENCES OF THE OVERDOSE CRISIS HAVE MADE IT ABSOLUTELY CLEAR THAT WE CAN NO LONGER NEGLECT NEITHER THE IMPORTANCE OF ADDRESSING RESEARCH TO COME UP WITH SOLUTIONS BOTH FOR SUBSTANCE USE DISORDER AND PAIN, AND THAT'S ULTIMATELY WHAT THE HEAL INITIATIVE DOES. I'M GOING TO BE CONCENTRATING PREDOMINANTLY ON THE ELEMENTS OF THE RESEARCH THAT TARGET OVERDOSES RESULTANT FROM THE USE OF SUBSTANCES AND OPIOIDS, WHILE ALSO ADDRESSING THAT MANY OF THESE OVERDOSES AND SUBSTANCE USE DISORDERS ARE CONCOMITANT AND CO-MORBID WITH THE EMERGENCE OF PAIN AS WELL AS OTHER MENTAL HEALTH DISORDERS. THEY DO NOT -- RARELY DO THEY OCCUR IN ISOLATION. THE SLIDE HERE, I USE TO GIVE YOU A SENSE OF WE WHERE ARE CURRENTLY WITH THE LATEST NUMBERS FROM CDC AS IT RELATES TO OVERDOSE DEATHS IN OUR COUNTRY OVER A PERIOD OF 12 MONTHS THAT ENDS ON 12/20/23, AND IT'S BEEN IN THE NEWS BECAUSE EVEN THOUGH THE NUMBERS ARE GIGANTIC, 107,543 PEOPLE IN THE UNITED STATES HAVE DIED FROM AN OVERDOSE, THIS IS ACTUALLY WHICH REPRESENTS MORE THAN ONE OVERDOSE DEATH PER EVERY FIVE MINUTES. AND THESE OVERDOSE DEATHS, WHAT MAKES THEM VERY TRAGIC IS NONE OF THEM SHOULD HAVE HAPPEN. THEY TEND TO OCCUR IN INDIVIDUALS THAT ARE 24 TO 44 YEARS OF AGE, WHICH ACTUALLY HAS DEVASTATION -- DEVASTATING EFFECTS TO THEM, OF COURSE THEIR FAMILIES, AND MANY OF THEM, THEIR YOUNG CHILDREN. BUT WHAT WE HAVE BEEN HEARING IN THE NEWS WITH THE LATEST REPORTS IS THAT THERE HAS BEEN FOR THE FIRST TIME EVER A REPORT OF REDUCTION IN THE NUMBER OF OVERDOSE DEATHS TO 3.14% OVER THE PAST YEAR, WHEN COMPARED TO THOSE OF 12/20/22. IT'S NOT A LARGE NUMBER, BUT IT'S NOTABLE BECAUSE WE HAVE EVERY SINGLE YEAR, WE HAVE SEEN THOSE NUMBERS IN RED GOING UP AND UP AND UP. AND FINALLY, WE WANT TO BE OPTIMISTIC AND ADDRESS MAYBE WE'RE REACHING PLATEAUS AND CERTAINLY AS A RESPONSE OF MANY OF THE INTERVENTIONS THAT HAVE BEEN LAUNCHED WHILE AT THE SAME TIME RECOGNIZING THAT THE NUMBERS ARE STILL ENORMOUS. THE OTHER COLUMNS ACTUALLY IDENTIFIED WHAT ARE THE TYPES OF DRUGS THAT WERE ASSOCIATED WITH THE OVERDOSE -- THE PERSON THAT DIED FROM AN OVERDOSE. IN MANY INSTANCES, PEOPLE THAT DIE FROM OVERDOSES HAVE MORE THAN ONE DRUG AND THAT'S WHY WHEN YOU ADD UP THE COLUMNS, IT'S ACTUALLY MORE THAN 107,543 BECAUSE, FOR EXAMPLE, MORE THAN 75% OF THOSE PEOPLE THAT DIED WITH AN OVERDOSE FROM COCAINE AND MORE THAN 65% OF THOSE THAT DIED FROM AN OVERDOSE FOR METHAMPHETAMINE HAD FENTANYL IN THEM. AND REALLY, FENTANYL IS THE MAIN DRIVER OF THE OVERDOSE DEATHS, AND IT'S ESTIMATED THAT PERHAPS MORE THAN 75% OF ALL OF THE OVERDOSE DEATHS CONTAINED FENTANYL. MOST OF THE TIME, IN ASSOCIATION WITH OTHER DRUGS. AND ONLY 10% OF PEOPLE THAT DIE FROM OVERDOSES ARE DYING FROM OPIOID ANALGESIC MEDICATION, WHICH IS VERY, VERY DIFFERENT FROM WHEN WE STARTED IN 2000, AND CERTAINLY IT HAS CHANGED QUITE DRAMATICALLY, PARTICULARLY OVER THE PAST, I WOULD SAY, SINCE 2015, 2016, AND THEN ACCELERATED THOSE CHANGES DURING THE COVID PANDEMIC. AND THIS IS IMPORTANT FOR US AT HEAL, WHEN WE TRY TO IDENTIFY WHAT ARE THE RESEARCH AREAS THAT WE NEED TO COVER IN ORDER TO PREVENT OVERDOSES FROM HAPPENING, AND TO HELP PEOPLE ACHIEVE RECOVERY. WE KNOW FROM THE PERSPECTIVE OF WHAT IS DRIVING OVERDOSE DEATH THAT THE MAJORITY -- THAT THE GROUP THAT IS AT HIGHEST RISK FOR OVERDOSE DEATHS ARE PEOPLE THAT HAVE AN OPIOID USE DISORDER, AND WE ARE LUCKY JUST TO HAVE MEDICATIONS FOR TREATING OPIOID USE DISORDER THAT ARE VERY EFFECTIVE, WHICH ARE THOSE MEDICATIONS? NALTREXONE, METHADONE AND BUPRENORPHINE. AND HOW EFFECTIVE ARE THESE MEDICATIONS? YOU CAN SEE BY THE FIGURE TO THE RIGHT THAT IDENTIFIES THE NUMBER OF AVERTED OVERDOSES BASED ON THE NUMBER OF WEEKS THAT PREGNANT WOMEN WERE BASICALLY SUSTAINED ON BUPRENORPHINE TREATMENT. AND YOU CAN SEE THE PREGNANT WOMAN WAS RETRAINED IN TREATMENT FOR 40 WEEKS, THEY ACTUALLY REDUCE THEIR OVERDOSES. THESE ARE KNOWN FATAL OVERDOSES, BY 97%. IT'S HARD TO THINK OF OTHER MEDICATIONS OVERALL THAT HAVE SUCH A LARGE EFFECT SIZE, BUT IT INDICATES MEDICATIONS FOR OPIOID USE DISORDER IF YOU PROVIDE THEM TO THE PATIENTS AT THE CORRECT DOSES AND YOU SUSTAIN THEM IN TREATMENT, YOU ACTUALLY HAVE VERY EFFECTIVE INTERVENTIONS. UNFORTUNATELY, THE NUMBER OF PEOPLE THAT COULD BENEFIT FROM THESE MEDICATIONS THAT GET THEM IS VERY, VERY SMALL. AND THE LATEST NUMBERS THAT HAVE BEEN PUBLISHED IS 22% OF THOSE WITH AN OPIOID USE DISORDER RECEIVE THESE MEDICATIONS. AND THIS HAS BEEN A PROBLEM SINCE THE HEAL INITIATIVE STARTED IN 2018. AND SO ONE OF THE ELEMENTS THAT WE HAVE PRIORITIZED IS IMPLEMENTATION SCIENCE TO HELP ACTUALLY INCREASE THE NUMBER OF PEOPLE THAT CAN BE PLACED ON MED KAIGS FOR OPIOID USE DISORDER AND RETAINED IN TREATMENT. IT WAS CLEAR FROM DATA FROM CDC AND FROM OTHER RESEARCH DONE BY NIDA FUNDED INVESTIGATORS THAT THE NUMBER OF SPECIALIZED TREATMENT TO ADDRESS OPIOID USE DISORDERS IN THE UNITED STATES IS ABSOLUTELY INADEQUATE TO TAKE CARE OF THE NUMBER OF PEOPLE THAT SUFFER FROM AN OD AN OPIOIE DISORDER, BUT IT IS ALSO CLEAR THAT THERE IS NO JUSTIFICATION, SCIENTIFIC OR MEDICAL, TO ACTUALLY HAVE A SEPARATE SYSTEM TO ADDRESS THE TREATMENT OF SUBSTANCE USE DISORDER VERSUS THAT OF OTHER MEDICAL CONDITIONS. WHICH HAS BEEN THE CASE IN THE UNITED STATES. WE'VE SEPARATED THE TREATMENT OF SUBSTANCE USE DISORDERS INTO SPECIALIZED CENTERS. AND AS A RESULT OF THAT, WE'VE MISSED THE OPPORTUNITY OF TAKING ADVANTAGE OF THE STRONG OVERALL HEALTHCARE INFRASTRUCTURE THAT EXISTS IN OUR COUNTRY. SO CERTAINLY ONE OF OUR TOP PRIORITIES IN IMPLEMENTATION SCIENCE OVERALL HAS BEEN IN CLINICAL RESEARCH ENGAGEMENT OF THE HEALTHCARE PROVIDERS INTO DEVELOPMENT OF MODELS OF CARE IN HEALTHCARE SETTINGS THAT CAN BE UTILIZED TO INITIATE PEOPLE ON MEDICATIONS FOR OPIOID USE DISORDER AND RETAIN THEM. AND THIS HAS BEEN THE PRIORITY FOR THE CLINICAL TRIALS NETWORK, AND AS A RESULT OF THAT RESEARCH, IT HAS BEEN A ACCELERATED FROM FUNDING WHICH HAS BEEN MADE POSSIBLE BECAUSE OF THIS FUNDING. WE HAVE ACTUALLY BEEN ABLE TO START TO MODIFY THE CULTURE OF HEALTHCARE SYSTEMS SO THAT NOW, FOR EXAMPLE, THROUGH RESEARCH DONE BY THE CTN, THERE ARE MULTIPLE EMERGENCY DEPARTMENTS IN THE UNITED STATES THAT ACTUALLY ARE SCREENING AND TREATING PEOPLE WITH -- INITIATING THEM ON BUPRENORPHINE IN THE EMERGENCY DEPARTMENT ITSELF, AND THEN LINKING THEM TO TREATMENT. SIMILARLY THROUGH RESEARCH FRO FROM -- FUNDED IN VERY MUCH PART THROUGH HEAL, WE HAVE BEEN ABLE TO SHOW AND DOCUMENT THAT THE PRIMARY CARE PHYSICIANS ACTUALLY ARE BASICALLY -- CAN PLAY AN IMPORTANT ROLE IN IDENTIFYING AND INITIATING TREATMENT AND SUSTAINING PATIENTS IN TREATMENT FOR AN OPIOID USE DISORDER, SO THIS BECOMES VERY, VERY RELEVANT WHEN WE THINK ALSO OF THE NEW OPPORTUNITY THAT DR. BERTAGNOLLI SPOKE ABOUT YESTERDAY, ABOUT THE PRIMARY CARE RESEARCH NETWORK THAT WE HAVE, TO HAVE IT DIRECTLY AND INTIMATELY INVOLVED AND ENGAGED IN THE TREATMENT OF INDIVIDUALS WITH SUBSTANCE USE DISORDER IN GENERAL. SIMILARLY, ENGAGING INFECTIOUS DISEASE DOCTORS AND DEVELOPING COMPLETELY NEW MODELS OF CARE THROUGH THE HEALTHCARE SYSTEM THAT CAN BE UTILIZED TO PROVIDE WITH MEDICATIONS SUCH AS DEPLOYMENT OF MEDICATIONS AND OVERSIGHT THROUGH PHARMACIES, THROUGH MOBILE UNITS, THROUGH TELEHEALTH, ALL OF THESE HAS BEEN POSSIBLE NOW WITH EVIDENCE THAT HAS BEEN COLLECTED THROUGH RANDOMIZED CLINICAL TRIALS DONE THROUGH THE CTN. THE OTHER IMPORTANT INFRASTRUCTURE THAT EXISTS IN OUR COUNTRY THAT IF WE TOOK ADVANTAGE OF IT COULD ENABLE US EXPANDING ACCESS FOR MEDICATION TO PEOPLE WHO NEED IT IS OF COURSE THE JUSTICE SETTINGS. WHETHER IT IS JAILS, PRISONS OR INDIVIDUALS ON PAROLE, THIS IS AN INCREDIBLE OPPORTUNITY TO FIRST SCREEN THEM TO SEE IF THEY HAVE AN OPIOID USE DISORDER AND, IF SO, PROVIDE THEM WITH TREATMENT. HOW IMPORTANT IS THE POTENTIAL IMPACT OF JUSTICE SETTINGS? WELL, LOOK AT THOSE NUMBERS FROM LAST YEAR IN WHICH THEY ACTUALLY DOCUMENTED THAT 25%, 1 IN 4 PEOPLE THAT DIED FROM AN OVERDOSE HAD A PRIOR JUSTICE INVOLVEMENT, 25 OF% OF THEM. AND HAD THEY BEEN RECOGNIZED AND PLACED IN TREATMENT ON MEDICATION, IT IS VERY LIKELY THAT THEY MAY HAVE NOT DIED. THERE WAS A STUDY THAT WAS DONE THAT ACTUALLY INITIATED MEDICATIONS FOR OPIOID USE DISORDER IN JAILS AND PRISON FOR EVERYONE THAT NEEDED IT, AND THEN THEY EVALUATED THE IMPACT OF THAT INTERVENTION, AND THEY SHOWED AT THE STATE LEVEL THAT THERE WAS A REDUCTION OF 31% IN OVERDOSES. SO THIS IS HOW IMPACTFUL INTERVENING IN JUSTICE SETTINGS CAN BE. BEFORE WE INITIATED THIS JUSTICE COMMUNITY INNOVATION NETWORK THROUGH HEAL FUNDING, MOST OF THE JAILS AND PRISONS IN THE COUNTRY DID NOT PROVIDE ACCESS TO MEDICATIONS FOR OPIOID USE DISORDERS. AND THOSE THAT DID IT DID IT IN VERY CONSTRAINED FASHION AND ONLY FOR ONE MEDICATION, AND THERE WAS NO FOLLOW-UP FOR THOSE PEOPLE WHEN THEY WERE RELEASED OUT OF JAILS AND PRISONS. THROUGH THE DEVELOPMENT OF THE JCOIN, IT HAS BEEN POSSIBLE TO ACTUALLY SEE WHEN IT WAS STARTED IN 2019 TO 2024, WE HAVE SEEN SIGNIFICANT EXPANSION IN THE NUMBERS OF JAILS AND PRISONS THAT ARE NOW PROVIDING MEDICATIONS AVAILABLE. YOU CAN SEE DATA FROM 2019 TO 2022, WE DON'T HAVE THE DATA FOR 2024, BUT OVERALL, THERE IS A HIGHER UPTICK FOR SCREENING FOR OPIOID USE DISORDER AND THERE'S ALSO A HIGHER PERCENTAGE, THIS IS FOR JAILS THAT OFFER MEDICATIONS FOR OPIOID USE DISORDER. SO THE INTERVENTIONS BY ENGAGING THTHE PEOPLE THAT ARE INVOLVED N JAILS THEMSELVES WITH INTEGRATIONS WITH ACADEMICIANS HAS ENABLED AN INCLUSION AND THE ACCELERATION OF ACCEPTANCE OF THESE TREATMENTS TO PROVIDERS. SO WHAT HAS THE JCOIN DONE? IT HAS BASICALLY FOCUSED ON TWO ASPECTS. ONE OF THEM IS BUILDING THE EVIDENCE OF INTERVENTIONS THAT CAN BE DONE IN JAIL OR IN TRANSITION FROM JAIL INTO THE COMMUNITY. AND THE SECOND ONE IS BUILDING CAPACITY SO THAT THE INDIVIDUALS AND PRACTITIONERS IN JUSTICE SETTINGS CAN BE ACTIVELY INVOLVED IN RESEARCH. AND AS A RESULT OF THAT, BASED ON THIS NETWORK, IT HAS BEEN POSSIBLE TO SHOW PARTICULARLY IMPLEMENTATION OF BUPRENORPHINE IN EITHER ONE MONTH BEFORE THEY ARE RELEASED OR WHEN THEY COME INTO THE JAIL, AND PARTICULARLY IMPLEMENTATION OF EXTENDED RELEASE BUPRENORPHINE MEDICATIONS SIGNIFICANTLY IMPROVE OUTCOMES. IT PREVENTS PEOPLE FROM OVERDOSING, WHICH IS VERY, VERY HIGH RISK WHEN THEY LEAVE JAILS OR PRISONS SINCE THEY DON'T HAVE ANY TOLERANCE LEFT. AND THE SECOND ONE IS IT PREVENTS REINCARCERATION. SO IT'S A WIN-WIN, AND AS YOU PROVIDE EVIDENCE AND YOU WORK JOINTLY WITH THE INDIVIDUALS INVOLVED IN JUSTICE SETTINGS, YOU START TO SEE AN EMBRACING OF THESE POLICIES. I DO WANT TO HIGHLIGHT JCOIN WAS DONE IN PARTNERSHIPS, NOT JUST WITH ONDCP, BUT IN PARTNERSHIP WITH THE BROAD JUSTICE ADMINISTRATION, JUSTICE, STATISTICS, SAMHSA AND PRISONS, AND THAT HAS CREATED COLLABORATIONS THAT WE DID NOT HAVE IN THE PAST. FINALLY, THE THIRD LARGE INITIATIVE THAT WE LAUNCHED IS ONE THAT TAKES ADVANTAGE OF COMMUNITIES, AND AGAIN THIS WAS SOMETHING THAT DR. BERTAGNOLLI HIGHLIGHTED YESTERDAY IN HER PRESENTATION, WE NEED TO ACTUALLY ENGAGED MUCH, MUCH MORE ACTIVE COMMUNITIES. SUCH AS THIS ONE WHERE THEY ARE LEADING THE DEVASTATION OF THE OVERDOSE CRISIS. THESE COMMUNITIES HAVE NOT STAYED PASSIVELY. THEY BASICALLY ENGAGE WITH ONE ANOTHER TO TRY TO COME WITH SOLUTIONS. SO THIS IS WHAT THE HEALING COMMUNITIES STUDY AIMED TO DO, ACTUALLY FORMALIZE AND FACILITATE INTERACTIONS THAT COMMUNITIES HAVE WITH HEALTHCARE SYSTEMS, WITH JUSTICE SETTINGS, WITH THE STATE, WHILE PROVIDING THEM AND FACILITATING THEM ACCESS TO DATA SO THAT THEY CAN ON THE ONE HAND EVALUATE THE MAGNITUDE OF THE PROBLEM AND ITS CHARACTERISTICS, EVALUATE THE RESOURCES THAT THEY HAVE, AND CHOOSE IN PARTNERSHIP WITH ACADEMICIANS AMONG A MENU OF EVIDENCE-BASED PRACTICES THAT ARE TARGETED NUMBER ONE TO IMPROVE PRACTICES FOR THE MANAGEMENT OF PAIN, NUMBER TWO, TO INITIATE SCREENING AND INITIATION OF MEDICATIONS FOR OPIOID USE DISORDER, AND NUMBER THREE, TO EXPAND ACCESS TO NALOXONE, WHICH IS THE MEDICATION YOU USE TO REVERSE OVERDOSES. THIS WAS A RANDOMIZED 66 COMMUNITIES -- 67 COMMUNITIES FROM FOUR OF THE STATES WITH THE HIGHEST OVERDOSE RATES IN THE COUNTRY. MASSACHUSETTS, OHIO, KENTUCKY AND NEW YORK. OF THESE 67 COMMUNITIES, BOTH RURAL AND URBAN, THEY WERE RANDOMIZED, ONE OF THEM RECEIVED THE IMPLEMENTATION FROM THE HEALING COMMUNITIES AND THE OTHER ONE WAS JUST AS USUAL INTERACTIONS. AND THAT STUDY WAS STARTED ON JANUARY 2020. LO AND BEHOLD, MARCH 2020 COMES AROUND AND COVID HITS US. SO DESPITE COVID, WHICH LED ACTUALLY TO CLOSING FOUR RESEARCHERS, THE PRISON SYSTEMS AND JAIL SYSTEMS, YOU MAY IMAGINE WERE BASICALLY SOME OF THE SITES WITH THE HIGHEST RATES OF MORTALITY FROM COVID. SO MANY OF THE RESEARCHERS WERE NOT ALLOWED TO IMPLEMENT THE INTERVENTION, SO THIS DELAYED THE INTERVENTION. WHICH WAS AIMED TO ACTUALLY BE DONE OVER ONE YEAR. SO WE EXPANDED TO 18 MONTHS, AND AT THE END OF THOSE 18 MONTHS, THERE WAS INTERVENTION FOR THE HEALING COMMUNITY WAS GIVEN TO THE OTHER COMMUNITIES WHICH WERE DESIGNED AS WITH TWO COMMUNITIES AND THERE WAS COMPARISON INITIALLY BETWEEN WAVE ONE AND WAVE TWO. NOW WE HAVE THE RESULTS FINALLY. WHAT I CAN TELL YOU IS, YES, THE WAVE ONE COMMUNITIES HAVE SIGNIFICANTLY HIGHER NUMBER OF PEOPLE THAT WERE INITIATED INTO MEDICATIONS FOR OPIOID USE DISORDER. THERE WERE SIGNIFICANT INCREASES IN THE EXPANDED ACCESS TO NALOXONE AND DISTRIBUTION OF NALOXONE. THERE WAS ALSO IMPROVEMENT IN PRACTICES FOR MANAGEMENT OF PAIN. AND WE NOW ALSO HAVE THE MAIN OUTCOME, WHICH WAS FOR THIS INTERVENTION ACTUALLY REDUCE THE NUMBER OF OVERDOSES. THESE ARE THE RESULTS. NOW, KEEP IN MIND THAT THE INTERVENTION WAS DEPLOYED OVER 18 MONTHS AMIDST THE COVID PANDEMIC. WHAT WAS SHOWN WAS THERE WAS INDEED A REDUCTION IN OVERDOSE DEATHS IN WAVE ONE, WHICH IS THE ONE THAT GOT THE INTERVENTION FIRST. AND THAT WAS A 9% REDUCTION BUT IT WAS NOT SIGNIFICANT. IF YOU LOOK AT IT IN TERMS OF THE STATES, WHAT COMES ACROSS VERY STRONGLY IS THAT THERE ARE DIFFERENCES. ALL OF THE STATES SHOW A REDUCTION BUT NOT KENTUCKY. AND YET KENTUCKY IS ONE OF THE STATE THAT HAS BEEN MORE PROACTIVE IN PROVIDING ACCESS TO TREATMENT FOR SUBSTANCE USE DISORDERS. SO WHEN I THINK ABOUT WHY I SAID WE DID NOT SEE AN EFFECT IN KENTUCKY, ONE OF THE ANSWERS THAT AT LEAST I GET TO MY BRAIN WHICH IS SPECULATIVE IS THAT KENTUCKY ALREADY HAS AN INFRASTRUCTURE THAT WAS PROVIDING THE TREATMENT THAT THE OTHERS AT THE -- AT THE LEVEL THAT THE OTHER STATES HAVE NOT. AND THAT'S WHY THAT INTERVENTION HAD A LARGER EFFECT ON THE OTHER STATES. WHAT WAS INTERESTING, AND THIS WAS A SECONDARY NOTE, A PRIORI OUT COME THAT WAS SEEKED OUT, THEY DID REPORT DECREASE IN OVERDOSE DEATHS FROM THE COMBINATION OF OPIOID AND PSYCHOSTIMULANTS. IN THIS CASE, PSYCHOSTIMULANTS PERTAIN PREDOMINANTLY TO METHAMPHETAMINE AND THAT SHOWED A 37% REDUCTION. AND AS I THINK ABOUT IT, I MEAN, WHAT IS IT THAT DRIVES THAT? I BELIEVE THAT THAT REDUCTION IS PREDOMINANTLY PERHAPS, AGAIN SPECULATIVE ON MY PART, DRIVEN BY THE EXPANDED ACCESS TO NALOXONE. BECAUSE RIGHT NOW, CURRENTLY, THE WHOLE UNITED STATES, THE ILLICIT DRUG SUPPLY IS FREQUENTLY CONTAMINATED WITH FENTANYL, SO PEOPLE THAT ARE SEEKING OUT METHAMPHETAMINE OR COCAINE THAT DON'T HAVE PER SE AN OPIOID USE DISORDER CAN DIE FROM AN OVERDOSE FROM FENTANYL, AND IN THEM, OF COURSE, FENTANYL CAN SAVE THEIR LIVES. WHY IT WE NOT SEE A SIGNIFICANT EFFECT? I THINK THAT CLEARLY ONE OF THE ASPECTS WAS 18 MONTHS SUFFICIENT, WERE WE HAVING TOO LARGE OF AN EXPECTATION OF WHAT ONE CAN ACHIEVE IN A PERIOD WHERE THERE WAS ALSO A MASSIVE EXPANSION OF CONTAMINATION OF THE ILLICIT DRUG MARKETS WITH FENTANYL, AND ALSO WITH OTHER DRUGS. SO -- BUT OVERALL, WHAT WE -- WE LEARNED ALSO THAT THERE ARE -- I MEAN, MANY LESSONS LEARNED, AND WHAT IS INTERESTING, AND JUST -- DR. BERTAGNOLLI AND I WERE COMMENTING JUST BEFORE, THERE HAS BASICALLY REPORTS STATING THAT IN THREE OF THESE FOUR STATE, NOW WE ARE OBSERVING REDUCTIONS IN OVERDOSE DEATHS. SO THE EXTENT TO WHICH THE PRACTICES THAT WERE LEARNED BY THE HEALING COMMUNITY STUDIES ARE ACTUALLY CHANGING THE WAY THE STATES ARE INTERVENING IS LIKELY TO BE A DOWNSTREAM EFFECT. MEANWHILE, WE HAVE METHADONE, BUPRENORPHINE, AND NALTREXONE, AND WE HAVE NALOXONE TO REVERSE OVERDOSES AND THESE ARE VERY EFFECTIVE, BUT THEY ARE NOT SUFFICIENT. SO WE ARE ALSO VERY AWARE OF THE NEED OF ALTERNATIVE IP INTERVENTIONS TO REVERSE OVERDOSES. THIS IS BECAUSE -- AND I'M NOT GOING TO GO INTO THE DETAILS, BUT REVERSAL OF FENTANYL OVERDOSES HAS ITS OWN CHALLENGES. AND PARTICULARLY WHEN YOU HAVE TO REVERSE SOMEONE THAT HAS A METHAMPHETAMINE AND HIGH DOSES OF METHAMPHETAMINE AND FENTANYL, NALOXONE MAY NOT BE SUFFICIENT IN THOSE INSTANCES. SO WE DON'T HAVE ANYTHING LIKE THE MEDICATIONS THAT WE HAVE FOR OPIOID USE DISORDER, FOR COCAINE OR METHAMPHETAMINE, NOTHING. NOTHING HAS BEEN APPROVED BY THE FDA. SO WE ARE TARGETING RESEARCH TO ADDRESS THAT GAP NEED, AND ONE VERY EXCITING PROJECT IS THE USE OF MOLECULES THAT CAN TRAP METHAMPHETAMINE AND FENTANYL IN THE BLOOD VERY, VERY RAPIDLY, INTERFERING THEN THEIR DELIVERY INTO THE SORT OF RESPIRATORY CENTERS INTO THE BRAIN. SO THAT IS ONE EXAMPLE, THE USE OF MONOCLONAL ANTIBODIES ALSO TO TRAP RAPIDLY THESE SUBSTANCE IS ANOTHER ONE, THE USE OF MONOCLONAL ANTIBODIES THAT HAVE LONG LASTING HALF LIVES CAN ALSO BE SEEN AS A TREATMENT FOR METHAMPHETAMINE USE DISORDER OR ALSO OPIOID USE DISORDER OR COCAINE USE DISORDERS. THERE'S ALSO A LOT OF EXCITEMENT IN THE WHOLE MENTAL HEALTH FIELD OF POWER OF NEUROMODULATION TECHNOLOGIES, WHETHER THEY ARE NONINVASIVE LIKE TMS OR DIRECT ELECTRICAL CURRENT STIMULATION OR INVASIVE LIKE DEEP BRAIN STIMULATION. IN THE DEVELOPMENT OF NEW TECHNOLOGIES LIKE LOW INTENSITY OR HIGH INTENSITY ULTRASOUND THAT CAN BE USED TO SPECIFICALLY TARGET THOSE CENTERS IN THE BRAIN THAT HAVE BEEN AFFECTED BY DRUGS AND THAT WE KNOW ARE DIRECTLY INVOLVED IN MANY OF THE SYMPTOMATOLOGY. AND SOME OF THE THIS RESEARCH, ACTUALLY INTERESTING HOW SCIENCE LEANS AND COMES TOGETHER IN WAYS THAT ARE UNPREDICTABLE ARE POSSIBLE BECAUSE OF FINDINGS FROM THE BRAIN INITIATIVE, WHICH ACTUALLY HAS HELPED US IDENTIFY THOSE CONNECTIONS IN THE BRAIN, AND HAS ALSO PRIORITIZED RESEARCH FOR TOOLS TO MODIFYING THOSE SYSTEMS. SO THAT'S A VERY EXCITING AREA, AND THERE'S DATA THAT HAS ACTUALLY SHOWN VERY PROMISING RESULTS, VERY PRELIMINARY, FOR THE TREATMENT OF INDIVIDUALS WITH OPIOID USE DISORDERS, SEVERE OPIOID USE DISORDER WITH THESE TECHNOLOGIES. AND THEN IT'S ALSO -- IT'S BEEN OBVIOUSLY CLEAR FROM WHAT THE CHARACTERISTICS OF THE OVERDOSES, THAT WE NEED TREATMENT FOR POLYSUBSTANCE USE DISORDERS. IT IS VERY RARE TO HAVE A PERSON THAT ONLY USES ONE SUBSTANCE, AND IT'S ALSO FROM WHAT WE KNOW IN SCIENCE, IT'S NOT THAT YOU HAVE VERY SPECIFIC CIRCUITS THAT ARE DISRUPTED BY ONE DRUG OR NOT THE OTHER. SO TARGETING THAT COMMON ELEMENT LIKE FOR EXAMPLE, AS I HAVE HERE SOME EXAMPLES, PEPTIDES, RECEPTOR ANTAGONISTS, MGLUR5, THOSE ARE EXAMPLES OF MOLECULES OR DRUGS ACTUALLY AIMED TO TREATING ADDICTION IN GENERAL, REGARDLESS OF WHAT TYPE OF DRUG. AND THE BEAUTY OF SOME OF THESE LIKE THE PEPTIDE RECEPTOR AGONIST IS THAT THEY ARE ALREADY APPROVED BY FDA FOR OTHER INDICATIONS AS RECEPTOR AN TALLNISTS ANTAGONISTS. SO IF RESEARCHERS SHOW THERE IS A BENEFIT WITH RANDOMIZED CLINICAL TRIALS, THEN IT WILL BE EASIER TO GET APPROVAL FASTER FOR TREATMENT OF SUBSTANCE USE DISORDER. NOW, IN THE LAST TWO PARTS OF MY PRESENTATION, I JUST WANT TO HIGHLIGHT THE ELEMENT THAT I STARTED BY SAYING WE'RE ALL EXCITED BY A 3% DECLINE IN OVERDOSE DEATHS. BUT I DO WANT TO POINT THE FACT THAT THE OVERDOSE DEATHS ACTUALLY AND THE WAY THAT IT'S CHANGING IS ACTUALLY QUITE HETEROGENEOUS. AND WHILE WE'RE SEEING SIGNIFICANT IMPROVEMENT IN SOME AREAS LIKE IN WHITE AMERICANS THAT IS DISPLAYED HERE, I'M SHOWING THE OVERDOSE DEATHS BY RACE/ETHNICITY, EXPRESSED PER 100,000 OF THE POPULATION. WHIELT WHITEWATER PEOPLE, YOU WHITE PEOPLE, THEY'RE GOING DOWN. LOOK AT THE BLACK AMERICANS, THEY HAVE 50% HIGHER RATE OF OVERDOSE MORTALITY. AND THEN LOOK AT THE AMERICAN INDIAN ALASKA NATIVE, THEY HAVE DOUBLED THE RATE OF OVERDOSE MORTALITY. AND WHAT IS ALSO NOTABLE, YOU DON'T SEE ANY PLATEAUING IN THOSE CURVES. THEY ARE GOING WAY UP. SO THE INTERVENTIONS THAT WE'RE DOING THAT WHILE THEY MAY BE BENEFICIAL FOR A LARGE SEGMENT OF THE WHITE POPULATION, THEY ARE NOT NECESSARILY POSITIVELY INFLUENCING YET UNDERREPRESENTED GROUPS. SIMILARLY, IF YOU LOOK AT WHAT STARTED THE WHOLE OVERDOSE CRISIS, WHICH WAS THE NEGLECT OF PAIN SYNDROMES THAT PUT PEOPLE AT RISK FOR SEEKING OUT SORT OF DRUGS THAT COULD ALLEVIATE THOSE PAINS, WE ALSO CAN SEE THAT THE AMERICAN INDIAN ALASKA NATIVES ARE OVER, OVERREPRESENTED AND YET OUR RESEARCH DONE ON NATIVE AMERICANS AND ALASKA NATIVES ACTUALLY HAS BEEN VERY DIFFICULT TO PENETRATE CERTAINLY OVERALL AT THE NIH. SO WE'RE TAKING PERHAPS ONE OF THE BOLDEST INITIATIVES TO BRING CAPACITY AMONG TRIBES AND TRIBE-SERVING ORGANIZATIONS TO ACTUAL LITTLE ENABLE THEM AND EMPOWER THEM TO DO RESEARCH THAT CAN BE TARGETING TO ADDRESS THE DEVASTATING CONSEQUENCE OF THE OVERDOSE CRISIS IN THESE COMMUNITIES, AND ALSO ADDRESS THE NEED THAT THEY HAVE FOR BETTER MANAGEMENT OF PAIN AND THIS IS WELCOME TO THE NATIVE COLLECTIVE RESEARCH EFFORT TO ANNOUNCE WELLNESS, N CREW, WE'RE GOING TO BE PROVIDING THE FUNDING THIS YEAR FOR INITIALLY A TWO-YEAR -- IT'S DIVIDED INTO TWO PHASES, PHASE ONE WILL BE TWO YEARS, TO ALLOW THAT COMMUNITY COMMUNITIES TO FORM NETWORKS AND PARTNERSHIPS AND DEVELOP PROJECTS AND BASED ON THAT COMPETE TWO YEARS FROM NOW TO ACTUALLY BE ABLE TO DEPLOY THEM. AND THEN THE OTHER GROUP THAT I WANTED TO ALL MAKE YOU AWARE BECAUSE IT ALSO FORCES US INTO LOOKING AT INITIATIVES THAT NEED TO BE ADDRESSED IN TERMS OF RESEARCH WHERE THERE IS NEED IS THAT OF AGE DEMOGRAPHICS. I MENTIONED THAT THE HIGHEST RATE OF OVERDOSES ARE BETWEEN 24 AND 44 YEARS OF AGE, WHICH IS WHEN PEOPLE ACTUALLY HAVE THE HIGHEST PREVALENCE OF OPIOID USE DISORDERS AND OTHER SUBSTANCE USE DISORDER, BUT DURING THE COVID PANDEMIC, WE SAW BASICALLY MORE THAN A DOUBLING IN OVERDOSE DEATHS AMONG ADOLESCENTS. AND ALSO, THAT'S IN THE UPPER ONE, AND LOOK AT THE LOWER ONE. WE ALSO STARTED SEEING SINCE 2015 A SIGNIFICANT RISE IN OVERDOSE MORTALITY ON PEOPLE THAT ARE MORE THAN 65 YEARS OF AGE. WHAT I CAN TELL YOU, PEOPLE MORE THAN 65 YEARS OF ALL OVERALL HAVE PROTECTION AGAINST SUBSTANCE USE DISORDER. SO THEY HAVE THE LOWEST RATES OF OVERDOSE MORTALITY IN GENERAL, AND THIS IS CHANGING. SO THE QUESTION IS, WHAT'S HAPPENING? AND IF WE LOOK AT IT AGAIN IN A WAY THAT'S SPECULATIVE BECAUSE WE DON'T HAVE RESEARCH THAT HAS BEEN ABLE TO DOCUMENT WHAT IS DRIVING THESE TRENDS IS THERE HAS BEEN A MAJOR CHANGE IN THE WAY THAT FENTANYL GETS INTO THE COUNTRY. AND IT IS DISGUISED IN ILLICIT MANUFACTURE -- PSYCHOTHERAPEUTICS, OPIOID, BENZODIAZEPINES. YOU CAN SEE THE NUMBER OF PILLS THAT HAVE BEEN SEIZED ENORMOUSLY DURING THE COVID PANDEMIC CONSISTENT WITH A VERY SIGNIFICANT ACCELERATION OF OVERDOSES, BOTH I IN ADOLESCENTS AND OLDER ADULTS. AND THEY DO SEEK OUT PSYCHOTHERAPEUTICS, AND IT IS VERY LIKELY THAT JUST BY THE FACT THAT YOU CAN GET THESE THINGS IN THE WEB AND THEY ARE LOWER COST THAN THE REAL THING, THAT EITHER THEY PURCHASE THESE THEMSELVES OR THEY ARE GIVEN TO THEM BY FRIENDS. AND ELDERLY PEOPLE THAT MAY NOT BE ABLE TO GET THEIR PAIN MEDICATIONS, AGAIN, HIGHLIGHTING WHY WE CANNOT NEGLECT IT, MAY SEEK OUT THESE IN THE WEB AND PUTTING THEM AT RISK. AND I ALSO WANT TO PAY ATTENTION TO THIS BECAUSE I DO THINK THAT WE CAN SORT OF NEED TO FOCUS ON IT, IF YOU LOOK AT THE CURVES OF PEOPLE THAT ARE 65 YEARS OF AGE, LOOK AT THE CURVE THAT JUMPS AT YOU AT HAVING THE HIGHEST MORTALITIES. THESE ARE BLACK OLDER AMERICANS THAT ARE ACTUALLY DYING THE MOST. SO WE -- WITHIN THIS LAND SCALE ACTUALLY REALLY NO DEMOGRAPHIC IS BEING SPARED IN OVERDOSE DEATH. IT BECOMES CLEAR THAT ADDRESSING TREATMENT OF OPIOID USE DISORDERS AND OTHER USE DISORDERS IS CRUCIAL BUT IT'S NOT SUFFICIENT. WE NEED TO ADDRESS PREVENTION INTERVENTIONS THAT ARE TARGETING WHETHER IT IS AN ADOLESCENT OR OLDER PERSON, IN ORDER TO PROTECT THEM FROM GETTING THEIR HANDS ON THESE ILLICITLY MANUFACTURED PILLS. THIS ENTAILS WE WORK VERY, VERY CLOSELY WITH DEVELOPMENT OF INTERVENTIONS FOR PATIENTS THAT ARE SUFFERING FROM PAIN BY ITSELF, OR IN PAIN CO-MORBID WITH A SUBSTANCE USE DISORDER, BECAUSE OTHERWISE, WE ARE ALWAYS GOING TO BE HAVING AND FIGHTING AGAINST THIS OVERDOSE CRISIS. IT ALSO REQUIRES THAT WE RECOGNIZE THAT WHILE TREATMENT AND RECOVERY IS THE IDEA, THERE ARE INSTANCES WHERE PATIENTS DON'T WANT TO BE IN TREATMENT AND IN THE MEANTIME, WE NEED TO DEVELOP INTERVENTIONS THAT CAN PROTECT THEIR LIVES, SO THAT EVENTUALLY WE CAN BRING THEM INTO TREATMENT. AND THAT'S ULTIMATELY WHAT THE HEAL IS AIMING TO DO, ACTUALLY EXPANDING AND DIVERSIFYING THE AREAS OF RESEARCH, WHERE THERE IS NEED OF MORE EVIDENCE, AND ACCELERATING THE DEVELOPMENT OF THIS EVIDENCE INTO PRODUCT THAT CAN BE DEPLOYED FOR TREATMENT AND PREVENTION OF THOSE THAT ARE AT RISK. THANKS VERY MUCH FOR YOUR ATTENTION, AND I THINK THAT NOW WE GO TO DR. WALTER KOROSHETZ. >> THANK YOU VERY MUCH, NORA, AND SO TH I'M THE DIRECTOR OF NS SPEAKING ON BEHALF OF A LARGE GROUP OF IC DIRECTORS WHO ARE INVOLVED IN THE HEAL INITIATIVE WITH A FOCUS ON THE CROSS-CUTTING THINGS THAT NORA ENDED UP WITH ABOUT HOW TO TREAT PAIN AND PEOPLE WHO HAVE OVERUSE DISORDER, HOW TO TREAT CHRONIC PAIN AND PREVENT OPIOID OVERUSE DISORDER, AND WE RUN THE PROGRAM ON THE PAIN SIDE WITH TWO OTHER CO-CHAIRS, DR. LINDSAY CRISWELL FROM NIAMS AND HELENE LANGEVIN FROM NCCIC. AND JUST TO SAY THAT WE STARTED TAKING OVER THIS AFTER LARRY GAVE IT UP ABOUT -- JUST A LITTLE LESS THAN A YEAR AGO, BUT EVERYTHING YOU HEARD SO FAR WAS REALLY SET UP BY DR. TABAK IN THE FIRST FIVE YEARS OF THE HEAL INITIATIVE SO HE HAS TO TAKE SOME OF THE HEAT ON THIS ONE. OKAY. SO NORA KIND OF SET UP THE ISSUE THAT'S FACING THE COUNTRY WITH THE OPIOID OVERUSE DEATHS AND THIS STARTED DUE TO, UNFORTUNATELY, THE MEDICAL SYSTEM THE OVERPRESCRIBING OPIOIDS. PEOPLE THOUGHT THAT THESE LONG-ACTING OPIOIDS WERE NOT GOING TO BE SO ADDICTIVE. NOT SO. WE MADE MISTAKES BY THIS BEFORE. I DON'T KNOW IF PEOPLE KNOW, BUT HEROIN WAS FIRST MARKETED AS A MEANS TO REDUCE ADDICTION DUE TO MORPHINE. SO WE'VE BEEN HERE BEFORE, AND THE QUESTION IS, IN HEAL, WHERE THE L STANDS FOR HELPING AND ADDICTION LONG TERM, IS THAT REALLY THE ONLY WAY OUT OF THIS MESS ON THE LONG TERM IS TO TRY AND DEVELOP BETTER MEANS OF MANAGING PAIN WITHOUT PUTTING PEOPLE AT THE RISK OF ADDICTION. UNTIL WE GET TO THAT STATE WHEN WE CAN REPLACE THESE OPIOIDS IN THE ARMAMENTARIUM, I THINK WE'RE GOING TO BE CONTINUOUSLY FACING THESE PROBLEMS. AS NORA SAID, WHAT HAS HAPPENED OVER THE LAST FIVE TO SIX YEARS IS THAT THERE'S BEEN AN EXPLOSION IN DEATHS DUE TO ILLICIT DRUGS, AN ACTUAL FACT IS NORA KIND OF ENDED UP WITH THE DEATHS IN PEOPLE -- THE ELDERLY AND ACTUALLY IF YOU LOOK AT THE NUMBERS, THE DEATHS DUE TO PAIN PILLS HAVEN'T CHANGED. THEY BASICALLY PLATEAUED, BUT THE MARKET HAS NOW BEEN PLACED WITH FENTANYL, SO WE STILL HAVE PEOPLE DYING BECAUSE THEY CAN'T GET THEIR PAIN TREATED AND THEY THEN MOVE TO OPIOIDS. NOW, SEPARATE FROM THE OVERDOSE CRISIS, PAIN IS A HUGE PROBLEM IN THE U.S. AND FOR PEOPLE WITH CHRONIC PAIN, THERE ARE REALLY NOT VERY GOOD TREATMENTS. OPIOIDS ARE REALLY GOOD FOR ACUTE PAIN, NONSTEROIDALS FOR ACUTE PAIN, BUT TAKING THESE THINGS CHRONICALLY PUTS YOU AT RISK FOR LOTS OF PROBLEMS AND ACTUALLY THE EVIDENCE SUGGESTS THAT CHRONIC OPIOID USE ACTUALLY MAKES CHRONIC PAIN WORSE, NOT BETTER. BUT PAIN IS COMMON, THEY COME TO THEIR PHYSICIAN, PRIMARILY PRIMARY CARE PHYSICIANS, AND IF YOU'VE GOT TO SEE A PATIENT 15 MINUTES AND THEY GOT PAIN, THEY'RE GOING TO LEAVE THE OFFICE PROBABLY WITH A PRESCRIPTION FOR A PAIN MEDICINE. AND SO WE REALLY NEED TO KIND OF CHANGE THE SYSTEM TO TRY TO ATTACK THE PROBLEM OF BOTH PAIN AND OPIOID USE DISORDERS AND HATS OFF TO MONICA THAT THIS IS REALLY A PROBLEM IN THE PRIMARY CARE SETTING. WE'LL TALK A LITTLE BIT ABOUT THE LACK OF PAIN SPECIALTY IN A SECOND. SO THE PROBLEM IS TREMENDOUS IN TERMS OF NUMBERS WHERE YOU'RE TALKING ABOUT 24 MILLION PEOPLE IN THE U.S. WITH CHRONIC PAIN. MANY IN WHICH THE CHRONIC PAIN IS ACTUALLY PROHIBITING THEM FROM DOING WHAT THEY WANT TO DO WITH THEIR LIFE, AND IT ALSO AFFECTS PEOPLE OF ALL DIFFERENT AGES BUT IT TENDS TO BE PEAKING IN MID LIFE AND THEN GOES ON INTO THE ELDERLY, AND IT'S ASSOCIATED WITH A LOT OF CO-MORBIDITY. SO ONE THING TO KNOW IS THAT THE PEOPLE WITH CHRONIC PAIN, IF YOU LOOK AT THEIR COMORBIDITIES, THEY'RE KIND OF THE SICKEST PEOPLE IN THE COUNTRY, WHICH MAKES IT DIFFICULT TO DEVELOP NEW TREATMENTS BECAUSE YOU'VE GOT TO THREAD THAT NEEDLE AND NOT MAKE SOME OF THEIR OTHER CONDITIONS WORSE. THE COST OF CHRONIC PAIN IN THE U.S. IS GIGANTIC. IT'S ACTUALLY BIGGER THAN HEART DISEASE, STROKE, DIABETES, ARTHRITIS, DUE TO LOST WAGES AND LOST PRODUCTIVITY. SO IT'S A TREMENDOUS ECONOMIC PROBLEM. AND IT'S COMPLICATED, IT'S CHALLENGING FOR LOTS OF DIFFERENT REASONS, SOME OF WHICH ARE RELATED TO THE WAY REIMBURSEMENT OCCURS IN THE U.S., SO THERE'S BEEN A DERTH OF PEOPLE WHO SPECIALIZE IN THE TREATMENT OF CHRONIC PAIN. MANY OF THE REIMBURSEMENT FOR PAIN IS DEPENDENT UPON DOING PROCEDURES THAT CAN BE BILLED SO HEAVILY ON THE PROCEDURAL SIDE, BUT FOR PEOPLE WITH MOST OF THE CHRONIC PAIN CONDITIONS, THAT'S ACTUALLY NOT GOING TO HELP THEM, SO WE HAVE A PROBLEM THERE WITH ACCESS TO SPECIAL CARE. WE HAVE A LOT OF DISPARITIES ACROSS THE COUNTRY IN TERMS OF HOW PEOPLE ARE TREATED. SOME OF THESE ARE SOCIOECONOMIC, MANY OF THESE ARE ACTUALLY RURAL. THERE'S ACTUALLY PAIN IN RURAL AMERICA IS ACTUALLY A GREATER PROBLEM PER PERSON THAN IT IS IN URBAN AREAS. THERE'S VERY LIMITED TRAINING IN MEDICAL SCHOOL ABOUT HOW TO MANAGE PAIN, EVEN -- I'M A NEUROLOGIST, WE GOT VERY LITTLE TRAINING IN FORMAL MANAGEMENT OF PAIN. ALTHOUGH WE SEE A LOT OF PATIENTS WITH PAIN, THAT'S FOR SURE, BUT THE ACTUAL BODY OF KNOWLEDGE FOR TREATMENT WAS REALLY QUITE WEAK COMPARED TO, SAY, THINGS LIKE STROKE, THINGS LIKE THAT. THE WORKFORCE AS I MENTIONED IS A PROBLEM, AND ACTUALLY MANY OF THE PAIN SPECIALISTS IN THIS COUNTRY ARE ACTUALLY HITTING RETIREMENT AGE AND THERE'S A BIG WORRY THAT THAT'S GOING TO MAKE IT HARD TO BUILD THE SPECIALTY BACK UP AGAIN, AND I TALKED ABOUT THE COMPLEXITY AND THE ISSUES ACROSS THE LIFESPAN. SO WITH THE HEAL INITIATIVE, WE HAVE THIS TREMENDOUS OPPORTUNITY TO DO SOMETHING IN THE PAIN SPACE THAT HAS REALLY TRANSFORMED WHAT NIH CAN DO HERE. SO WHAT HEAL DOES IS IT BRINGS -- IN ALL THE INSTITUTES, NOW THERE'S 14 INSTITUTES THAT SIT AROUND THE TABLE AND MAKE THE DECISIONS ON HOW TO MOVE THE PAIN FIELD FORWARD, BUT THE REASON THERE'S 14 INSTITUTES, BECAUSE THERE'S 14 INSTITUTES THAT HAVE PAIN PORTFOLIOS, AND SOME OF THEM ARE BIG, SOME OF THEM ARE SMALL, AND OUR KIND OF PHILOSOPHY HERE IS THAT WITH HEAL, WE CAN DO THINGS THAT ARE MORE TO THE RIGHT THAT NO SINGLE INSTITUTE CAN DO. HEAVILY ON THE THERAPY DEVELOPMENT, THERAPY TESTING, AND ALSO SOME PROJECTS THAT MAY BE MORE BASIC THAT NO ONE INSTITUTE CAN DO ON THEIR OWN. SO WE WANT THE INSTITUTES TO CONTINUE THE PAIN RESEARCH THEY'VE DONE IN THE PAST, BUT THIS ALLOWS THEM TO KIND OF PLUG IN TO A SYSTEM THAT MOVES THINGS MORE TOWARDS TRANSLATION. SO WE DON'T DO A LOT OF DISCOVERY OF NOVEL TARGETS, BUT WE WILL FUND VALIDATION OF NOVEL TARGETS TO THE POINT WHERE THEY CAN COME IN TO THAT PIPELINE, EITHER BE TAKEN BY INDUSTRY OR WORKED UP BY US TO DEVELOP NEW THERAPIES. SO WE HAVE TRANSLATIONAL THERAPEUTICS DEVELOPMENT PROGRAMS I'LL TALK TO YOU ABOUT. WE HAVE PLATFORMS FOR COMPANIES OR ACADEMICIANS THAT COME IN AND TEST THEIR DRUGS AGAINST DIFFERENT ANIMAL MODELS. WE HAVE NCATS WORKING CELL-BASED ASSAYS FOR PAIN MEDICATIONS. AND WE HAVE ALSO A GROUP THAT'S WORKING TO DEVELOP BETTER DEVICE MANAGEMENT OF PAIN, BETTER BIOMARKERS FOR DIFFERENT PAIN CONDITIONS. ONE OF THE MAJOR THINGS THAT KEEPS THE INDUSTRY OUT OF THE PAIN FIELD IS THAT THE OUTCOMES ARE -- ON A SCALE OF ONE TO 10, HOW BAD IS YOUR PAIN, WHICH IS NOT A REALLY GOOD WAY TO DEVELOP DRUGS. THE INDUSTRY IS JUST DESPERATE FOR BIOMARKERS OF TARGET ENGAGEMENT SO THAT THEY CAN UNDERSTAND WHETHER THEIR DRUGS ARE ACTUALLY HITTING THE TARGET BEFORE GOING INTO THESE EXPENSIVE KIND OF LARGE TRIALS BASED ON CLINICAL SUBJECTIVE MEASURES. WE SPEND QUITE A BIT OF EFFORT ON UNDERSTANDING BACK AND NECK PAIN. TURNS OUT THAT IF YOU LOOK AT THE GLOBAL DISABILITY ADJUSTED LIFE YEARS, THE GREATEST DRIVER OF DISABILITY ADJUSTED LIFE YEARS IS BACK AND NECK PAIN IN THE ENTIRE WORLD, LET ALONE THE UNITED STATES. NOT REALLY BEEN DEEPLY STUDIED BUT IN THE BAC PAC PROGRAM, WE'RE DOING THAT. CLINICAL TRIALS, TESTING NOVEL THERAPIES ALL THE WAY TO THERAPIES IN RURAL SETTINGS, IN HEALTHCARE SYSTEMS, LOOKING AT TRYING TO IMPROVE EQUITY, HEALTH EQUITY IN PAIN, AND THEN AS NORA ENDED UP WITH, HOW TO REALLY DEAL WITH THIS REALLY TOUGH PROBLEM WITH TREATING PAIN IF PEOPLE HAVE OPIOID OVERUSE DISORDER. SO ONE OF THE CHALLENGES IN TERMS OF DEVELOPING THE THERAPIES WAS THAT THERE WAS A REAL RETREAT BY THE INDUSTRY FROM DEVELOPING NEW PAIN THERAPEUTICS. THIS WAS DRIVEN HEAVILY BY THE HEAVY RISK AND LOSSES THAT THEY TOOK WHEN THEY TRIED TO DEVELOP THESE PROGRAMS, WERE FOUND TO HAVE SIDE EFFECTS AND THE FDA SHUT THEM DOWN. SO WE WORK WITH THE FDA AND OUR PHILOSOPHY IS TO WORK WITH BIOTECHS OR ACADEMICIANS OR IN NICHE AREAS WHERE THE RISK TO BENEFIT RATIO IS MORE CLEAR AND THE FDA FEELS MORE COMFORTABLE APPROVING PRODUCTS IN THOSE NICHE AREAS THAN IT WOULD, SAY, FOR A PILL THAT 25 MILLION PEOPLE ARE GOING TO TAKE THE NEXT DALE FOR ANY KIND OF PAIN. SO THAT'S KINDS KIND OF OUR PHILOSOPHY. NCATS IS A REALLY FABULOUS PROGRAM DEVELOPING NEW THERAPEUTICS WITH CELL ASSAYS. I MENTIONED -- WILL MENTION A COUPLE OF THE OTHER THINGS THAT WE DO. WE HAVE DEVELOPED -- WE DEVELOPED THIS IN NINDS AND THEN WE ALSO OPENED IT UP FOR ALL THE NEUROSCIENCE INSTITUTES AND BLUEPRINTS FOR NEUROSCIENCE AND NOW FOR THE HEAL INITIATIVE, IT'S A PROGRAM WHERE WE HELP ACADEMICIANS AND BIOTECH COMPANIES MOVE THEIR PRODUCTS TO THE POINT WHERE THEY CAN GET AN IND FROM THE FDA. SO THERE'S MANY DIFFERENT STAGES WHICH THIS GOES THROUGH, AND WE'VE BEEN LUCKY TO BE ABLE TO HIRE PEOPLE IN FROM THE PHARMACEUTICAL INDUSTRY WHO HELP US DO THIS, AND WHAT WE DO IS WE SET UP CONTRACTS WITH DIFFERENT CROs SO THAT THE INVESTIGATOR GETS MONEY TO WORK OUT OF THEIR LAB, BUT THE BIG ADVANTAGE IS THEY GET ACCESS TO DO THE PK, THE PD, THE TOXICOLOGY WITH THE CRO, SO THEY HAVE ACCESS TO COMPANIES THAT HELP THEM MOVE ALONG THIS PATH TO GET AN IND. WE ALSO HAVE THIS PLATFORM FOR SCREENING PAIN MEDICATIONS IN MULTIPLE DIFFERENT ANIMAL MODELS TO ENSURE THAT THE DATA YOU GET IS REALLY RIGOROUS, BECAUSE THEY'RE DOING THESE MODELS EVERY DAY, THEY KNOW EXACTLY HOW THESE MODELS ARE GOING TO PERFORM, AND THEN YOU CAN TEST AND SEE WHAT YOUR DRUG DOES IN MULTIPLE DIFFERENT MODELS THAT AK ACADEMIC LAB REALLY WOULDN'T BE ABLE TO DO ON THEIR OWN AND MOST BIOTECHS CAN'T DO ON THEIR OWN EITHER SO WE THINK THIS WILL BE HELPFUL IN THE FIELD. THERE'S VERY MUCH INTEREST BY THE PHARMACEUTICAL COMPANIES TO TRY AND UNDERSTAND PAIN MECHANISMS IN HUMANS, FEELING THAT THEY GOT TOTALLY BURNT IN THE PAST BY RELYING ON ANIMAL MODELS OF PAIN. ON THE OTHER HAND, THERE'S NO PAIN MED THAT'S MARKETED THAT DIDN'T WORK IN ANIMALS BUT THERE'S A LOT OF MEDS THAT WORKED IN ANIMALS THAT DIDN'T WORK IN HUMANS, SO THAT'S WHERE THIS COMES FROM. BUT INTERESTINGLY, THERE ARE NOW WAYS IN WHICH WE CAN GET INFORMATION FROM HUMANS ON THEIR PAIN ME CAN NICHES, AND THIS WAS ONE OF THEM, WHICH I WAS REALLY QUITE SURPRISED THAT THIS COULD WORK, BUT THERE ARE CONDITIONS WHERE YOU CAN TAKE DORSAL ROOT GANGLION, YOU CAN GET AUTOPSY MATERIAL FROM PEOPLE WHO HAVE DIED, LOOKING AT HOW PAIN CHANGES THE CIRCUITS, SO THE BEST INSTANCE IS A PAPER THAT SHOWS WHERE YOU TAKE THE DORSAL ROOT GANGLION CELLS OUT, PUT THEM IN CULTURE AND YOU RECORD FROM THEM, THEY'RE VERY QUIET IF YOU DON'T HAVE PAIN IN THAT DISTRIBUTION OF THE NERVE, BUT IN PEOPLE WHO HAD RADICULOPATHY, THOSE NERVES WERE FIRING CONTINUOUSLY AND IT'S A REALLY STRIKING DIFFERENCE, WHICH AGAIN WAS QUITE SURPRISING, BUT IT REALLY GOES TO THE HUMAN CONDITION. AND SO THE PROGRAMS THAT WE HAVE, THIS IS A LIST, WE REALLY ARE CAREFUL ON WHAT WE PICK. THESE ARE ALL WHAT WE CALL MILESTONE PROJECTS, SO THEY'RE JUST LIKE ANYTHING THAT WOULD OCCUR IN A DRUG COMPANY. IF YOUR FORMULATION IS NOT GOOD AND IT'S NOT GETTING INTO THE BLOODSTREAM, YOU GET SHUT DOWN AND YOUR PROJECT STOPS. SO WE HAVE A NUMBER THAT HAVE BEEN DISCONTINUED, BUT WE HAVE HAD PRETTY GOOD SUCCESS IN GETTING INDs AND ALSO ON THE DEVICE SIDE FROM GETTING DEVICES THAT ARE GETTING IDEs FOR PAIN MANAGEMENT. NORA YOU HEARD YESTERDAY AND JOHN AND I ABOUT WORK THAT'S BEING DONE TO RECORD FROM THE BRAIN AND TO TRY AND GET IN THIS CASE SIGNATURES OF PAIN, SO INSTEAD OF WHEN I FEEL PAIN, YOU KNOW, HOW MUCH IS IT, ONE, TWO, THREE, FOUR, TURNS OUT THAT AT LEAST IN THIS STUDY, THIS THEY WERE ABLE TO SEE AN OSCILLATION IN THE ORBITOFRONTAL GYRUS IN PEOPLE WHO WERE INSTRUMENTED IN THEIR RECORDING FROM THE BRAIN TISSUE THAT INDICATED WHEN THE PERSON WAS IN PAIN. NOW THIS IS NOT SOMETHING THEY DO JUST TO RECORD FROM INSIDE SOMEONE'S BRAIN, BUT IT'S DONE TO DEVELOP A CLOSED LOOP SYSTEM WHEREBY WHEN YOU SEE THAT SIGNAL, YOU CAN STIMULATE THE BRAIN TO TURN OFF THE PAIN. THERE WAS A PRESENTATION BY A GENTLEMAN WHO HAD ONE OF THESE PLACED AT THE UNIVERSITY OF CALIFORNIA SAN FRANCISCO, IT WAS REALLY QUITE STRIKING. WHAT HE SAID WAS, I'VE HAD CHRONIC PAIN FOR I DON'T KNOW HOW MANY YEARS, BUT HE SAID I CAN FEEL IT COMING AND THEN, BOOM, IT GOES AWAY. AND IT GOES AWAY FROM THE STIMULATOR TURNS ON. SO THESE CAN BE QUITE EFFECTIVE IF WE CAN UNDERSTAND IN THE INDIVIDUAL PERSON WHERE TO GO, BUT IT'S A REALLY NICE EXAMPLE OF HOW THE BRAIN INITIATIVE AND HEAL WORK TOGETHER IN ADDITION TO WHAT NORA MENTIONED IN TERMS OF THE ADDICTION CIRCUIT. SO AS I SAID, WHAT WE'D LIKE TO DO IS IMPROVE THE MANAGEMENT OF PAIN IN MULTIPLE DIFFERENT AREAS THAT WILL IMPROVE THE HEALTH OF THE COUNTRY. SO WE HAVE A NUMBER OF DIFFERENT CLINICAL TRIAL NETWORKS SET UP AND THESE AGAIN ARE THINGS THAT NO INSTITUTE COULD HAVE DONE ALONE. CERTAINLY NOT AT THIS SCALE. BUT WE HAVE EFFECTIVENESS STUDIES THAT ARE GOING ON, MOSTLY IN ACADEMIC CENTERS. LOOKING AT DIFFERENT MEDICATIONS, DIFFERENT NON-PHARMACOLOGICAL TREATMENTS. WE HAVE A PRISSMM NETWORK FOR PRAGMATIC AND IMPLEMENTATION STUDIES THAT'S GOING ON PRIMARILY IN HEALTHCARE SYSTEMS RUN BY NCCIH. I SHOULD HAVE SAID THAT EFFECTIVENESS NETWORK HAVE BEEN RUN THROUGH NCATS THROUGH THEIR CTA PROGRAMS, THE PRISSMM IS RUN THROUGH HEALTHCARE NETWORKS AND LOOKING ALMOST ENTIRELY RIGHT NOW AT NON-PHARMACOLOGICAL TREATMENTS, ONE OF WHICH IS ACUPUNCTURE FOR THE ELDERLY WITH BACK PAIN, THAT'S ACTUALLY DONE IN COLLABORATION WITH CMS, AND OF COURSE THEY'RE LOOKING FOR DATA ON APPROVING THIS AND OTHER KINDS OF TREATMENTS FOR PAIN. THESE ARE THE CONDITIONS THAT WE'RE CURRENTLY STUDYING, SO WE'RE HEAVILY WEIGHTED ON THE CHRONIC PAIN SIDE FOR THE IMPLEMENTATION STUDIES. BACK PAIN IS CERTAINLY ONE OF THE BIGGEST, AND THESE AS YOU CAN SEE ARE THE NETWORKS THAT WE HAVE GOING ON. ONE THAT RECENTLY GOT LAUNCHED, AND I FEEL BAD THAT IT TOOK SO LONG, IS A STUDY, A NETWORK TO STUDY PAIN IN CHILDREN. IT'S BEEN REALLY HEAVILY NEGLECTED, NOT VERY MUCH KNOWN ABOUT HOW TO DO THAT RIGHT, AND SO WE THINK THAT COULD MAKE A REALLY BIG DIFFERENCE. SO PACK PAIN, THERE'S A PROJECT CALLED BAC PAC, RUN PRIMARILY BY NIAMS. THIS IS TRYING TO DEEP PHENOTYPE PEOPLE WITH BACK PAIN TO TRY AND FIND OUT WHAT ARE THE DIFFERENT PHENOTYPES, HOW TO SUBSET THEM AND UNDERSTAND WHAT TREATMENT WORKS BEST FOR WHAT PARTICULAR PHENOTYPE. WE HAVE AS I MENTIONED A CONCERN ABOUT THE WORKFORCE, AND SO WE'VE PUT A LOT OF EFFORT INTO DEVELOPING YOUNG INVESTIGATORS COMING INTO THE FIELD OF PAIN RESEARCH, PARTICULARLY ON THE CLINICAL SIDE, ACTUALLY THE BASIC SCIENCE OF PAIN HAS EXPLODED, THE CLINICAL SIDE IS WHAT'S LAGGING SO WE REALLY NEED TO GET THOSE KIND OF MESHED TOGETHER. WE ACTUALLY HIRED AN EDUCATION COMPANY TO ACTUALLY TILE THESE TOGETHER. IT'S REALLY BEEN QUITE AMAZING, THEY KIND OF BUILT THIS COMMUNITY SPHERE AMONG THE YOUNG PEOPLE, GOT THEM MENTORS, GOT THEM COMING TO MEETINGS. THERE'S A LOT OF EXCITEMENT NOW IN THE FIELD, DOING SOMETHING THAT WITHOUT HEAL, I COULD NEVER HAVE THOUGHT ABOUT DOING. AND AGAIN, THE NEXT THING I WANT -- MAYBE THE LAST THING I WANTED TO MENTION IS THE DATA. SO LARRY THOUGHT REALLY HARD ABOUT WHAT HEAL SHOULD DO WITH DATA, AND I THINK HAD A REALLY FORWARD-LOOKING IDEA, WHICH WAS NOT TO PUT IT IN SOMEBODY'S CELLAR AND ASK PEOPLE TO GO AND GET IT WHEN YOU NEED IT, BUT TO BUILD A DATA ECOSYSTEM. AND THE IDEA ABOUT THIS ONE IS THAT AT NIH, EVERYONE HAS TO MAKE THEIR DATA AVAILABLE. THAT'S THE GOOD NEWS. THE BAD NEWS IS, GOOD LUCK FINDING IT. BUT WITH THIS SYSTEM, YOU HAVE A DATA ECOSYSTEM WHICH IS BASICALLY LINKING TO ALL THE DATABASES IN HEAL, SO YOU CAN PUT YOUR DATA IN MULTIPLE DIFFERENT AREAS AND THEN THE CENTRAL PORTAL IS BASICALLY DEVELOPING APIs TO LINK TO THESE DIFFERENT DATASET, AND THEN DEVELOPING THE TOOLS THAT YOU WOULD BE ABLE TO AN LIEDZ ANALYZETHEM ACROSS MULTIPLE DA . IT'S A PILOT, IT'S SOMETHING THAT SEEMS LIKE IT MIGHT BE A SOLUTION FOR BIGGER PROBLEMS OF HOW TO DEAL WITH DATA, NOT BRINGING IT CENTRALLY BUT LINKING THINGS TOGETHER AND WITH THESE KNOWLEDGE GRAPHS WHERE YOU CAN ACTUALLY THEN EXPLORE DATA IN DIFFERENT AREAS OF INTEREST RELATED IN THIS CASE TO PAIN AND OUD. I'M JUST GOING TO END UP BY SAYING THAT WE'RE NOW, AFTER FIVE YEARS OF THE HEAL INITIATIVE, AND AS OPPOSED TO THE OPIOID DISORDERS WHERE THERE'S A WHOLE INSTITUTE AND THEY'RE ALL ORGANIZED AND THEY HAVE STRATEGIC PLANS, THERE IS NO PAIN INSTITUTE. THE HEAL INITIATIVE IS ACTUALLY BRINGING ALL THAT TOGETHER, AND THE PLAN -- FROM ALL THE DIFFERENT INSTITUTES, PAIN INTEREST, SO WE'RE EMBARKING ON A STRATEGIC PLAN TO DEVELOP A ROAD MAP FOR GOING FORWARD. LIKE JOHN NGUI SAID YESTERDAY ABOUT THE ROAD MAP FOR THE BRAIN INITIATIVE, WE HAVE TWO CO-CHAIRS WORKING WITH OVER THE NEXT YEAR, THEN WE'LL BE WORKING WITH NORA TO KIND OF BRING TOGETHER WHAT'S COMING OUT OF THIS GROUP WITH HER STRATEGIC PLANNING AND PUT TOGETHER A UNIFIED STRATEGIC PLAN FOR THE HEAL INITIATIVE, BOTH THE PAIN AND THE OUD SIDE. SO IT'S REALLY BEEN AN EXCITING PROJECT. THAT'S ONE OF THE MOST FUN THINGS AT NIH, U.S. GET TO WORK WITH THE OTHER NIH DIRECTORS AND INSTITUTES AND THEIR FOLKS, AND I THINK IT'S BEEN THANKS TO LARRY AND FRANCIS WHO STARTED THIS, IT'S BEEN A REALLY GREAT PROGRAM. SO THANKS VERY MUCH. HAPPY TO ANSWER QUESTIONS. >> SO THANKS TO BOTH OF YOU. FOR ACKNOWLEDGING AND BLAMING ME FOR VARIOUS THINGS. AND THAT'S FAIR. I THINK WE WOULD BE REMISS IF WE DIDN'T ACKNOWLEDGE REBECCA BAKER, WHO REALLY WAS SO INSTRUMENTAL IN TYING THIS ALL TOGETHER. FIRST FOR FRANCIS AND THEN FOR ME. SINCE NEITHER FRANCIS NOR I REALLY HAD THE TIME THAT WAS NECESSARY. I THINK MOVING THE LOCUS OF CONTROL TO THE INSTITUTES WHERE THE RESOURCES WERE ALWAYS PLACED BECAUSE THAT'S WHERE CONGRESS PUT THEM MADE A LOT OF SENSE AS THE PROGRAMS MATURED, AND I THINK TODAY, YOU HAD THE OPPORTUNITY TO REALLY SEE HOW THESE THINGS CONTINUE TO EVOLVE IN A VERY SIGNIFICANT WAY, SO CONGRATULATIONS TO BOTH YOU, NORA, AND TO YOU, WALTER. THE ECOSYSTEM THAT YOU MENTIONED AT THE END HOPEFULLY HAS CATALYZED AN INTRODUCTION PROFESSIONALLY BETWEEN THE PAIN RESEARCHERS AND THE OPIOID USE DISORDER RESEARCHERS, HO I WHO I UNDERSTAND MAYBE HERETOFORE MAYBE PASSED THROUGH THE NIGHT BY ACCIDENT, BUT NOW SEEM TO HAVE A NASCENT, AT LEAST, MAYBE MORE, COMMUNITY OF INVESTIGATORS. I DON'T KNOW IF EITHER OF YOU WANT TO SPEAK TO THAT, BUT I THINK IT'S IMPORTANT TO GET THEM IN CONVERSATION WITH ONE ANOTHER. >> YEAH, I THINK DEFINITELY THAT ONE AND THE OTHER CROSS-CUTTING PIECES THAT I HAVE NOT SEEN AT THIS LEVEL BEFORE, I WOULD SAY THE PATIENT ENGAGEMENT PIECE ALSO IN HEAL REALLY OPENED MY EYES TO HOW MUCH YOU CAN IMPROVE WHAT YOU'RE DOING BY BRINGING PEOPLE WITH LIVED EXPERIENCE IN, SO WE'VE HAD A PROGRAM RIGHT FROM THE BEGINNING WHERE WE HAD HEAL COMMUNITY PARTNERSHIP COMMITTEE WITH PEOPLE WITH EXPERIENCE MEETING AND GIVING US INPUT, AND SO I THINK THAT WAS ANOTHER THING THAT I'M TRYING TO KIND OF PUT THAT INTO A LOT OF THE NINDS STUFF WE DO AFTER WHAT WE SAW IN HEAL. AND THEN I THINK OTHER PROGRAMS LIKE THE EMPOWER THAT SHE MENTIONED AND N CREW, WE'RE REALLY GOING OUT INTO THE COMMUNITY, NATIVE AMERICAN COMMUNITIES, AND TRYING TO MAKE A DIFFERENCE THERE. AND WE'RE DOING THAT TOGETHER. SO THERE'S A LOT OF CROSS COMMUNICATION AND WORK. >> AND THE ISSUE THAT I WOULD HIGHLIGHT, THOUGH, IS THAT TO YOUR QUESTION, LARRY, THE NOTION OF HAVING A DATA ECOSYSTEM THAT ALLOWS US TO EXPLORE HOW PATIENTS THAT ARE CLASSICALLY SEEN WITH PAIN OR WITH SUBSTANCE USE DISORDER INTERSECT. AND I THINK THAT THIS OPENS THE OPPORTUNITY TO START TO MERGE MORE AND MORE WHAT APPEARS TO BE A REALITY THAT IN GENERAL, MEDICAL CONDITIONS RARELY ARE IN ISOLATION, AND YET WE DIVIDE AND NOW WITH TOOLS WITH ACCESS TO DATABASES, WE CAN START TO UNDERSTAND HOW THEY INTERACT. WE HAVE KNOWN ALL ALONG THAT PEOPLE WITH A SUBSTANCE USE DISORDER HAVE A MUCH MORE HIGHER PREVALENCE OF PAIN THAN THOSE WITHOUT SUBSTANCE USE DISORDER. WE DIDN'T REALLY COMPLETELY UNDERSTAND WHY, BUT IT HAS BEEN RECOGNIZED AS A I HAOER RISK. ALSO WE KNEW PEOPLE THAT HAVE CHRONIC PAIN WHEN IT IS NOT PROPERLY TREATED ARE AT EXTREMELY HIGH RATE OF MISUSING SUBSTANCES BECAUSE THEY ARE TRYING TO ESCAPE THAT MENTAL STRESS. SO THE DATA ECOSYSTEM IS OPENING UP THAT VENUE FOR US TO TRY TO LOOK IN A MORE REAL WAY, THE WAY THAT DISEASES FREQUENTLY OCCUR TOGETHER AND TO TRY TO UNDERSTAND WHY AND HOW TO PROPERLY TREAT THEM. FLEURNL >> YES. >> THANK YOU VERY MUCH, VERY INTERESTING AND VITALLY IMPORTANT WORK. I'M JUST WONDERING ALSO THE POTENTIAL FOR COLLABORATION WITH THE CARE FOR HEALTH NETWORK BECAUSE THE RURAL CONNECTION MIGHT BE INTERESTING AND MAYBE PRIORITIZING TRIALS THAT ARE RELEVANT TO PAIN MAYBE IN THOSE CONTEXT, SO JUST CAME TO MIND AS I WAS LISTENING. AND QUESTION IS IT LOOKED TO ME LIKE THERE ARE MORE WOMEN WHO REPORT CHRONIC PAIN, BUT YET I GUESS WE HAVE MORE MEN WHO ARE OVERDOSING. I'M SURE YOU CAN CONNECT THE DOTS, BUT I'M JUST CURIOUS WHY DO YOU THINK THAT IS? >> WE'VE LOOKED AT IT FROM THE PERSPECTIVE OF WHY IS IT THAT THE OVERDOSE MAR TA MORE TALTS E TIMES MORE COMMON AMONG MALE THAN FEMALES. IT'S NOT THAT SUBSTANCE USE DISORDER IS THREE TIMES MORE COMMON AMONG MALES AND FEMALES, IT APPEARS TO BE MORE THAT THE MALES ENGAGE IN RISKIER BEHAVIORS THAT ACTUALLY INCREASES THE LIKELIHOOD THAT THEY MAY END UP WITH AN OVERDOSE, AND IT ALSO HAS BEEN RECOGNIZED OVERALL THAT WOMEN HAVE HIGHER PREVALENCE OF CERTAIN CHRONIC PAIN CONDITIONS. AND INDEED WHAT WAS INTERESTING WHEN THE OVERDOSE CRISIS STARTED IS THAT THE OVERDOSE DEATHS AMONG WOMEN THAT WERE BETWEEN 45 AND 54 WERE EQUIVALENT TO THAT OF MALES, WHICH WE HAVE NEVER SEEN THAT, AND IT WAS BECAUSE THEY WERE MUCH MORE LIKELY TO BE PRESCRIBED OPIOID MEDICATIONS. SO YES INDEED, AND AS TO YOUR POINT ACTUALLY, THE IMPORTANCE OF TARGETED INTERVENTIONS INTO THE RURAL AREA, THAT'S ABSOLUTELY A VERY GOOD SUGGESTION, AND WE'RE ALSO VERY EXCITED ABOUT THE PRIMARY CARE RESEARCH NETWORK, BECAUSE THAT WILL GIVE US FINGERS INTO A MUCH MORE VAST ARRAY OF RURAL COMMUNITIES THROUGH PRIMARY CAROL HEALTH PROVIDERS AND SO INDEED, THANKS FOR THAT SUGGESTION. >> BRIAN. >> I WAS CURIOUS ABOUT THE FINDING ABOUT THE MIXED DEATHS DUE TO METHAMPHETAMINE, COCAINE AND FENTANYL TOGETHER, AND I THINK THAT THE CHANNELS PROBABLY TO ADDRESS THOSE OVERDOSES LOOK PROBABLY DIFFERENT THAN MAYBE THEY WOULD IN PEOPLE WHO ARE EXPERIENCING CHRONIC PAIN OR CHRONIC -- OR LONG-STANDING USE OF OPIOIDS. I'M ASSUMING THAT'S MAYBE LIKE UNINTENTIONAL EXPO SEU EXPOSURD COCAINE AND THERE WAS FENTANYL MIXED IN, THEY DIDN'T KNOW IT, THERE MIGHT BE LESS CONSISTENT USE OF DRUGS BUT STILL HIGH OVERDOSE POTENTIAL AND I THINK THE APPROACHES TO ADDRESSING THAT ARE PROBABLY VERY DIFFERENT THAN SOME OF THE THINGS THAT WERE TALKED ABOUT HERE. SO I'M WONDERING IF YOU CAN SAY A LITTLE BIT ABOUT INITIATIVES TO SORT OF ADDRESS THAT PART OF THE -- VERY SUBSTANTIAL PART OF THE PIE AS IT COMES TO OVERDOSES. >> THANKS FOR ACTUALLY PICKING UP ON THAT WHOLE ISSUE, BECAUSE TECERTAINLY THE CHARACTERISTICSF INDIVIDUALS THAT ARE SEEKING OUT COCAINE OR METHAMPHETAMINE, WHETHER THEY HAVE A USE DISORDER OR NOT IS VERY DIFFERENT FOR THE TARGET INTERVENTIONS THAT WE HAVE WITH SOMEONE WITH AN OPIOID USE DISORDER. THAT'S WHY I ENDED UP WITH THAT SLIDE IN TERMS OF WE NEED TO ADDRESS PREVENTION THAT TARGETS THE DIVERSE DEMOGRAPHICS. AND CERTAINLY ONE OF THE KEY THINGS WE CURRENTLY HAVE IS TO TAKE EVERY OPPORTUNITY THAT WE HAVE TO PROVIDE WITH NALOXONE TO PEOPLE THAT COULD BE AT RISK. SO FOR EXAMPLE, METHAMPHETAMINE, AS YOU KNOW, IS USED AS SOMETIMES IN RELATIONSHIP WITH RISKY SEXUAL PRACTICES. SO IF INFECTIOUS DISEASE DOCTORS OR CLINICS CAN PROVIDE ALONG WITH THE MEDICATIONS FOR HIV NALOXONE, YOU COULD BE ABLE TO COVER THAT POPULATION. SO THAT'S WHERE IT BECOMES SO VERY CRUCIAL TO ENGAGE PHYSICIANS OR CLINICIANS WITH DIFFERENT SPECIALTIES. >> THAT SOUNDS REALLY PROMISING, I THINK ALSO PREP PROVIDERS AND -- YEAH, BECAUSE WE MONITOR FENTANYL EXPOSURE IN OUR COHORT, AND THE TRENDS ARE NOT SIGNIFICANT YET BUT WE'RE SEEING UPTAKE -- INCREASED UNINTENDED EXPOSURE IN YOUNG GUY A GAY AND BISEXUAL MEN IN CHICAGO, AND I DON'T THINK THERE'S JUST AWARENESS -- AND ALERTING PEOPLE THAT THEY MIGHT NEAT NALOXONE, PEOPLE THAT HAVE NO IDEA NA LOCATION OWN MIGHT BE SOMETHING THEY SHOULD BE HAVING ACCESS TO. >> BASICALLY IDENTIFYING WE'RE DOING THIS RESEARCH ON HARM REDUCTION PRACTICES, BECAUSE ONE OF THE INTERVENTIONS IS FENTANYL TEST STRIPS. SO THAT IF YOU DON'T WANT TO GET FENTANYL, YOU CAN ACTUALLY DETERMINE IF THE DRUG THAT YOU'RE BUYING HAS FENTANYL OR NOT. SO THIS IS THE TYPE OF INTERVENTION THAT WE'RE AIMING TO UNDERSTAND BETTER HOW TO DEPLOY IT. >> QUICK? YEP. WE HAVE A LITTLE COFFEE BREAK RIGHT NOW. WE'RE GOING TO TAKE A BREAK, GRAB SOME COFFEE, AND THEN WE'LL BE BACK TO HEAR A PRESENTATION ABOUT RECOVER. THANK YOU. >> OKAY, EVERYBODY, COME ON BACK. I THINK WE'RE READY TO MOVE ON. WE HAVE DR. HUGH AUCHINCLOSS THAT'S GOING TO START US OFF WITH OUR UPDATE ON LONG COVID, THE RECOVER PROGRAM. >> ARE YOU READY FOR ME TO GO? >> YEP. >> MY NAME IS HUGH AUCHINCLOSS, PRINCIPAL DEPUTY DIRECTOR AT NIAID. LET ME APOLOGIZE FOR BEING SOMETHING OF AN IMPOSTER HERE. WHEN THE RECOVER PROGRAM WAS FIRST FORMED, IT WAS IMAGINED THAT THE SENIOR LEADERSHIP WOULD BE THREE PEOPLE, GARY GIBBONS FROM HEART, LUNG AND BLOOD, WALTER KOROSHETZ FROM NEUROLOGY AND TONY FAUCI FROM NIAID. IT BECAME VERY APPARENT VERY QUICKLY THAT TONY WAS TOO BUSY WITH TOO MANY OTHER RESPONSIBILITIES. SO HE WAS REPRESENTED BY JOE GREEN, A PROGRAM OFFICER IN OUR INSTITUTE WHO'S BEEN FOLLOWING FOR MANY YEARS DEEPLY INVOLVED WITH THOSE ISSUES, SO HE REALLY REPRESENTED NIAID, HE WOULD BE HERE TODAY BUT HE'S OUT OF THE COUNTRY. RECENTLY, GEN JEANIE WOULD HAVEN HERE TODAY BUT SHE AS ALSO OUT THE THE COUNTRY. SO THEY HANDED ME SOME SLIDES AND SENT ME UP HERE TO INTRODUCE THE RECOVER PROGRAM. >> SO MAYBE, HUGH, CAN I INTERRUPT YOU JUST FOR A SECOND, BECAUSE I JUST ALSO WANT TO GIVE JUST A VERY BRIEF FRAMING OVERALL ON THE RECOVER INITIATIVE AND THE OVERALL LONG COVID WORK. I MEAN YOU ALL REALIZE, IT'S NOT BEEN VERY LONG SINCE THIS NEW DISEASE LANDED. IT REALLY IS A COMPLETELY NEW DISEASE. RECOVER NEEDED TO COMPLETELY DISCOVER -- BE ABLE TO UNDERSTAND THIS NEW DISEASE IN A WAY THAT COULD LEAD TO EFFECTIVE PREVENTION AND TREATMENT. AND THAT MEANT AT A LABORATORY FUNDAMENTAL BIOLOGY LEVEL, IT ALSO MEANT AT CLINICAL CHARACTERIZATION AND IN TREATMENT. SO WHAT RECOVER HAS DONE, WHICH YOU'RE GOING TO HEAR TODAY FROM THE TEAM HERE, HAS DONE THIS, CHARACTERIZED THIS COMPLETELY NEW DISEASE, AND PRODUCED A REALLY -- IT'S PRODUCED A WEALTH OF PRELIMINARY DATA THAT ALLOWS US TO THEN MOVE FORWARD IN THE NEXT WAVE, WHICH IS NOW GOING TO BE COMING AFTER THIS. SO THIS IS KIND OF OUR, YOU KNOW, INTERIM PROGRESS, READY TO GO, AND THEN MOVING FORWARD TO A NEW STAGE OF ENHANCED FOCUS, NOW THAT THIS DISEASE IS SO MUCH BETTER UNDERSTOOD ON TREATMENT AND PREVENTION. SO TAKE A LOOK AT THIS BECAUSE THIS IS THE ORIGINAL CHARACTERIZATION OF A BRAND NEW DISEASE THAT NEVER EXISTED. SO THANK YOU, HUGH. >> ACTUALLY THE FIRST TIME I HEARD THE TERM "LONG COVID" WAS FROM TONY FAUCI AND PARTLY BECAUSE OF HIS FRIENDSHIP WITH SENATOR KANE FROM VIRGINIA WHO DEVELOPED ONE OF THE FIRST CASES OF COVID IN THIS COUNTRY IN EARLY 2020. TONY HAD REGULAR CONVERSATIONS WITH HIM, AND WEEKS AFTER HE SUPPOSEDLY HAD RECOVERED FROM HIS INFECTION, HE WAS STILL COMPLAINING OF BRAIN FOG AND CHRONIC FATIGUE, AND VERY EARLY ON, PEOPLE THEN BEGAN TALKING ABOUT LONG COVID FOR SOME PEOPLE WHO GOT THE INFECTION, AND TONY -- NIAID AT THAT POINT, WE WERE VERY CONCERNED ABOUT PHENOTYPING THE PEOPLE WHO WERE GETTING INFECTED, TRYING TO FIGURE OUT WHY SOME PEOPLE STAYED LARGELY ASYMPTOMATIC AND OTHER PEOPLE WENT ON TO DEVELOP REALLY DISASTROUS RESPIRATORY SYMPTOMS. SO TONY SAID THEN, IF WE'RE PHENOTYPING THESE PEOPLE, WE SHOULD CONTINUE TO FOLLOW MANY OF THEM IN THE LONG TERM BECAUSE SOME OF THEM ARE GOING TO DEVELOP THIS NEW SYNDROME. SO IT TURNS OUT THAT AT THIS POINT, ABOUT 17% OF PEOPLE WHO ARE ADULTS IN THIS COUNTRY HAVE EXPERIENCED SYMPTOMS OF LONG COVID. THAT DOESN'T MEAN THAT 1 IN 6 ADULT AMERICANS AT THIS POINT HAVE LONG COVID BECAUSE SOME PEOPLE DO, IN FACT, IMPROVE. BUT IT'S A STAGGERING NUMBER TO REALIZE HOW MANY PEOPLE HAVE EXPERIENCED THIS SYNDROME. SO RECOVER WAS INITIATED IN 2021 WITH THE IDEA OF UNDERSTANDING LONG COVID AND THE LONG TERM CHRONIC ILLNESSES ASSOCIATED WITH POST INFECTION. SO WE REALLY FROM THE VERY BEGINNING THOUGHT THAT THERE WOULD BE OVERLAP BETWEEN THIS AND THE MACFS SYNDROME. THE KEY SCIENTIFIC AIMS WERE OF COURSE TO UNDERSTAND THE CLINICAL SPECTRUM OF THIS SYNDROME, TO DEFINE RISK FACTORS FOR WHO WOULD DEVELOP IT AND WHO WOULD NOT, TO STUDY THE PATHOGENESIS OVER TIME, AND TO IDENTIFY INTERVENTIONS AND TREATMENTS THAT WOULD PREVENT OR TREAT THE SYNDROME. SOME GUIDING PRINCIPLES INCLUDED THAT IT BE PATIENT-CENTERED, THAT IT BE NATIONAL IN SCOPE WITH AN EMPHASIS ON DIVERSITY, PARTICIPATION OF THE COMMUNITY, THAT WE WOULD WORK WITH PLATFORMS THAT USED COMMON DATA ELEMENTS AND STANDARDIZED METHODOLOGIES SO THE DATA COULD BE COMPARED ACROSS MULTIPLE STUDIES, AND THAT THERE WOULD BE AN ADAPTIVE APPROACH BASED ON EMERGING SCIENTIFIC INFORMATION. THE RECOVER PROGRAM TRULY HAS BEEN NATIONAL IN SCOPE WITH OVER 155 LOCATIONS ACROSS THE COUNTRY WHERE PEOPLE CAN BE ENROLLED. THERE ARE NOW MORE THAN 60,000 PATIENT RECORDS AND THERE ARE COHORTS THAT INCLUDE ADULTS, PREGNANT PEOPLE, PEDIATRIC POPULATIONS, AND AUTOPSIES. AGAIN, THE GUIDING PRIPS PEL PRINCIPLEFROM THE BEGINNING HASO ENGAGE THE PATIENTS WITH COMMUNITY REPRESENTATIVES THAT ARE PART OF THE PROCESS OF DEVELOPING THE SCIENTIFIC AGENDA AND THE RESEARCH PROTOCOLS. AND THIS HAS BEEN TRUE ALL THE WAY THROUGH INCLUDING COMMUNITY REPRESENTATIVES WHO CAN ALSO THEN REPRESENT MEMBERS OF THE PATIENT COMMUNITY. LET ME JUST BEGIN WITH A BRIEF CHARACTERIZATION OF SOME OF THE OBSERVATIONAL COHORTS THAT HAVE COME OUT OF THE RECOVER PROGRAM. THESE COHORTS HAVE ENABLED PROPOSED DEFINITIONS OF WHAT LONG COVID IS, WHICH IS A STANDARDIZED DEFINITION, AND THAT INCLUDES THE DEFINITION OF THE PEDIATRIC SYNDROME. WE HAVE LEARNED THAT VACCINATION REALLY DOES DECREASE THE RISK OF DEVELOPING LONG COVID. WE'VE DEMONSTRATED WITH THESE COHORTS THAT THERE IS A HIGHER PREVALENCE OF SYMPTOMS OF LONG COVID IN BLACK AND HISPANIC POPULATIONS. AND THERE'S BEEN QUITE A LOT OF INTERESTING WORK WITH IMMUNOLOGIC CHARACTERIZATION OF THE PATIENTS WHO DEVELOP LONG COVID. LET ME NOW TURN THIS OVER TO WALTER KOROSHETZ, WHO WILL TALK FURTHER ABOUT THE FINDINGS. >> THANKS, HUGH. YEAH, IT'S BEEN, AGAIN, AN AMAZING EFFORT PUTTING THIS TREMENDOUS PROGRAM TOGETHER, AND I'M GOING TO SAY NH -- IT'S BEEN ON THE BACKS OF NHLBI THROUGHOUT AND NIND AND NINDS HAS BEEN INVOLVED FROM THE BEGINNING AND REALLY PROUD OF WHAT'S BEEN ABLE TO HAPPEN. SO I'M GOING TO TAKE A LITTLE BIT OF OBJECTION TO WHAT WAS MENTIONED, THAT THIS IS ACTUALLY A NEW DISEASE. I THINK IT ACTUALLY IS AN OLD DISEASE, BUT WE'LL SEE. THE REASON WHY I SAY THAT IS BECAUSE NIND, PARTICULARLY JOE GREEN WHO WAS MENTIONED BY YOU AND NINDS FOLKS HAVE BEEN WORKING ON MYALGIC ENCEPHALOMYELITIS CHRONIC FATIGUE SYNDROME FOR A NUMBER OF DECADES, AND THE SYMPTOMS THAT PEOPLE WHO WITH LONG COVID HAVE EXPRESSED, ALMOST IDENTICAL TO WHAT PEOPLE WITH ME/CFS HAVE EXPERIENCED. THERE ARE DIFFERENCES, IT'S NOT CLEAR IF THE DIFFERENCES ARE RELATED TO THE TIME FRAMES IN WHICH WE'RE TALKING TO PEOPLE. MOST OF THE PEOPLE WITH ME/CFS, WE ARE LOOKING AT HAVE BEEN SICK FOR YEARS. LONG COVID PEOPLE HAVE BEEN SICK FOR MONTHS, A YEAR OR TWO, AND WE'LL HAVE TO SEE HOW THINGS PAN OUT OVER TIME, BUT THE NEUROLOGIC SYMPTOMS, MEMORY, WORD-FINDING DIFFICULTIES, CONCENTRATION DIFFICULTIES, EXECUTIVE FUNCTION DIFFICULTIES, THESE ARE THE BRAIN FOG THINGS THAT FOLKS COMPLAIN OF, BUT THESE ALSO OCCUR IN ME/CFS. SLEEP DISORDERS IN BOTH, PAIN SYNDROMES, MUSCLE/JOINT PAIN, ABNORMAL SENSATIONS. I THINK SENATOR KANE COMPLAINED OF A TINGLING AND PAIN IN HIS EXTREMITIES. STATIC TACHYCARDIA IS A SIGN OF AUTONOMIC TROUBLE. THE TASTE AND SMELL ARE PRIMARILY COVID RELATED BECAUSE COVID DOES AFFECT THE NASAL MUCOSA SO THAT WAS SOMEWHAT UNIQUE. THE CARDIOPULMONARY ISSUES INTERESTINGLY ARE EXERCISE AND TOLERANCE, SOMETHING THAT YOU SEE IN ME/CFS AND LONG COVID, BUT A LOT OF THE OTHER ONES, THE DYSPNEA, COUGH, CHEST PAIN, ARE -- AND MYOCARDITIS AND FIBROSIS ARE RELATED TO THE FACT THAT COVID REALLY DID SOME DAMAGE TO THE LUNG, AND IMPORTANTLY WHEN YOU LOOK AT LONG COVID, IT'S REALLY IMPORTANT TO SEPARATE PEOPLE WHO ARE IN THE HOSPITAL WHO HAD TISSUE DAMAGE WHICH HAD THE HIGHEST RISK OF DEVELOPING LONG COVID SYMPTOMS BUT MAYBE MORE ON THE CARDIOPULMONARY SIDE COMPARED TO THE PEOPLE WHO HAD MILD COVID, ACUTE SYMPTOMS, BUT THEN DEVELOPED LONG COVID. THEY'RE A LITTLE BIT DIFFERENT, AND ONE MIGHT EXPECT THAT BECAUSE IN ACTUAL FACT, COVID CAUSED ARDS, ARDS IS KNOWN TO CAUSE SERIOUS PROBLEMS THAT TAKE YEARS IF NOT LONGER TO REHABILITATE, AND SO THE INITIAL POST COVID CLINICS WERE BUILT FOR PEOPLE COMING OUT OF INTENSIVE CARE UNITS, BUT THE BIG SURPRISE WAS THEY WERE BEING FILLED BY PEOPLE WHO WERE NEVER IN THE HOSPITAL WHO HAD MILD DISEASE AND THEN THEY STARTED FILLING UP THESE CLINICS, SO THE MAJORITY OF PEOPLE WITH LONG COVID WERE NOT HOSPITALIZED FOLKS, AND THEY HAVE A LITTLE BIT OF A DIFFERENT SYNDROME. SO THERE WERE ALSO GASTROINTESTINAL, MENTAL HEALTH AND A NUMBER OF OTHER SYMPTOMS OPEOPLE COMPLAIN. NOW THE BIG QUESTION IS, WHAT IS CAUSING THIS PROBLEM? AND IN ME CSF, WE'VE NEVER BEEN ABLE TO GET TO THE BOTTOM OF IT. HOWEVER, IN ME/CFS, MOST OF THE EVIDENCE POINTS TO THE FACT THAT THE CONDITION STARTED WITH WHAT SOUNDED LIKE AN INFECTIOUS CONDITION, AND THEN PEOPLE JUST NEVER GOT BETTER OR THEY WOULD GO UP AND DOWN AND THEY WERE CONSTANTLY SICK FOR YEARS, AND IT WAS IMPOSSIBLE TO KIND OF FIGURE THIS OUT BECAUSE YOU WERE SEEING PEOPLE MONTHS OR YEARS AFTER WHAT THE INFECTION WAS, SO COVID IS KIND OF A NATURAL EXPERIMENT TO TRY AND GET AT THIS PROBLEM BECAUSE IN RECOVER, WHAT WE DID IS WE RECRUITED PEOPLE WHO WERE ACUTELY SICK SO WE COULD FOLLOW THEM AND FIND OUT WHAT DIFFERENTIATES THE PEOPLE WHO GET BETTER VERSUS THOSE WHO DON'T, AND WE COULD FIND PEOPLE AND RECRUIT PEOPLE WHO WERE SICK MONTHS OR A COUPLE MONTHS EARLIER WHO HAVE SYMPTOMS WITH THEIR APPROPRIATE CONTROLS. SO THIS IS A REAL -- THANK GOODNESS HOPEFULLY IT A ONCE-EVER OPPORTUNITY TO STUDY THIS CONDITION. BUT I THINK THAT'S REALLY WHAT OUR OPPORTUNITY IS HERE AND WANT TO MAKE THE MOST OF IT. RECOVER WAS PUT TOGETHER WITH THE IDEA THAT IT WAS GOING TO BE A HARD ONE LIKE ME/CFS HAS BEEN, AND SO TO DO KIND OF A LARGE EFFORT NOT TO LEAVE ANY STONE UNTURNED IS KIND OF HOW WE LOOKED AT THIS, WE THOUGHT THAT IF THIS WAS GOING TO BE A SIMPLE FIX, SOMEONE ELSE WOULD FIGURE IT OUT AND WE WOULDN'T BE IN THE SPOT WE'RE IN NOW, WHERE WE'RE YEARS LATER AND WE STILL DON'T REALLY UNDERSTAND WHAT THE PROBLEM IS, BUT WE HAVE THIS ARMAMENTARIUM, THIS ARMY OF DATA, PEOPLE, SAMPLES, AND INVESTIGATORS WHO ARE REALLY WORKING HARD ON THE PROBLEM. WE DON'T KNOW WHAT THE CAUSE IS, BUT AS I'LL SHOW YOU, PEOPLE HAVE FOUND LOTS OF ABNORMALITIES, PEOPLE WITH LONG COVID. THE MAJOR IDEAS THAT ARE COMING OUT IN TERMS OF DRIVERS ARE VIRAL REACTIVATION, SO WHEN YOU HAVE ACUTE COVID, YOU GET REACTIVATION OF MULTIPLE DIFFERENT VIRUSES THAT ARE DORMANT IN YOU, PARTICULARLY EPSTEIN BARR VIRUS, THE CAUSE OF INFECTIOUS MONONUCLEOSIS, AND OF COURSE INFECTIOUS MONONUCLEOSIS CAN CAUSE YEARS-LONG SYMPTOMS VERY SIMILAR TO CHRONIC FATIGUE SYNDROME, AND IS ACTUALLY A CAUSE OF LONG TERM CHRONIC FATIGUE SYNDROME, BUT THAT'S NOT THE ONLY ONE THAT GETS REACTIVATED. THE OTHER ONE IS PERSISTENT VIRAL INFECTION OR MAYBE PERSISTENT VIRAL ANTIGEN EMIA, NOT NECESSARILY INFECTION. THE IDEA HERE IS THAT YOU HAVE THE VIRUS, IT MAY TAKE A LONG TIME TO CLEAR THE ACTUAL REPLICATING VIRUS, AND SOME PEOPLE MAYBE WE CAN'T CLEAR IT. THAT'S AN OPEN QUESTION. THE OTHER OPTION IS THAT THE INFECTION IS SO PROMISCUOUS IN OUR BODIES THAT THERE'S ANTIGEN AND MEMBRANES IN MULTIPLE DIFFERENT CELLS, MULTIPLE DIFFERENT CELL TYPES AND THE IMMUNE SYSTEM IS CONTINUOUSLY RESPONDING TO THIS. THE THIRD ONE IS IMMUNE DYSREGULATION, SO A PRIMARY DEFECT, IMMUNE DYSREGULATION. VIRAL REACTIVATION, PERSISTENT VIRAL INFECTION AND PERSISTENT ANTIGENEMIA WILL DEFINITELY JAZZ UP THE IMMUNE SYSTEM, LEAD TO SECRETION OF LOTS OF THINGS THAT WE KNOW CAUSE FATIGUE LIKE CYTOKINES AND OTHERS, BUT THERE COULD ALSO -- BECAUSE COVID AFFECTS THE IMMUNE SYSTEM, BE A RESET OF THE IMMUNE SYSTEM THAT OCCURS IN SOME PEOPLE THAT LEADS TO THIS KIND OF CHRONIC POST INFECTIOUS SYNDROME. SO THERE HAVE BEEN STUDIES OF AUTOIMMUNITY IN MOST ACUTE SEQUELAE OF COVID. THERE ARE CERTAINLY STUDIES LIKE THIS ONE SHOWING EPITOPE OVERLAP BETWEEN THE VIRUS AND MULTIPLE PROTEINS THAT OCCUR NORMALLY IN PEOPLE. THERE'S A WHOLE BUNCH OF STUDIES, MOST OF THESE ARE SMALLER STUDIES THAT HAVE CLAIMED TO SEE SOME EVIDENCE OF AUTOIMMUNE ACTIVATION IN PEOPLE WITH LONG COVID. AND AGAIN, THE BEAUTY OF THE RECOVER PROGRAM IS WE HAVE 15,000 PEOPLE THAT WERE ENROLLED, AND WE CAN ACTUALLY TEST WHETHER THESE HYPOTHESES COMING OUT OF THE SMALLER STUDIES CAN BE SEEN ACROSS THE BOARD SO WE CAN VALIDATE THINGS THAT ARE M KOLLING UP FROM SMALLER STUDIES. THEN THE QUESTION IS WHETHER THERE IS PERSISTENCE OF VIRAL MATERIAL ACTUALLY ACTIVE VIRUS, AND GARY WILL TALK A LITTLE BIT ABOUT HOW WE LOOK AT THIS IN THE CLINICAL TRIAL, BUT THIS FIRST CAME OUT OF MICHELLE'S LAB WHERE THEY LOOKED AT INTESTINAL BIOPSIES AND SAW EVIDENCE OF VIRAL PERSISTENCE IN MULTIPLE PATIENTS WITH LONG COVID, AND ALSO SHOWED THAT THE IMMUNE SYSTEM, CHARACTERISTICS OF THE IMMUNE SYSTEM INDICATED THERE WAS STILL CLONAL GENERATION OF IMMUNE CELLS THAT LOOKED LIKE THEY'RE BEING STIMULATED BY CONTINUOUS EXPOSURE TO VIE US ARE. SO THE CLONES WERE CONTINUINGLY TO EVOLVE, SUGGESTED THAT THERE WAS STILL CHRONIC STIMULATION. THEN THERE WAS THIS STUDY FROM THE NATIONAL CANCER INSTITUTE IN INTRAMURAL NIH WHERE THEY LACKED AT AUTOPSIES OF PEOPLE WHO -- LOOKED AT AUTOPSIES OF PEOPLE WHO DIED WITH COVID OR DIED AFTER COVID. THE CAVEAT IS MOST OF THESE PEOPLE WERE PRETTY SICK. THESE WERE MOSTLY ALMOST ALL HOSPITALIZED PATIENTS, BUT THEY WERE ABLE TO FIND REPLICATING VIRUS OUT TO 230 DAYS OUT TO SYMPTOM ONSET, AND THERE WAS A PAUCITY OF INFLAMMATION EXCEPT FOR IN THE LUNG. SO THIS BROUGHT UP THE QUESTION EARLY ON THAT THERE COULD BE PERSISTENT VIRUS, WHICH WOULD THEN TRIGGER THE CLINICAL TRIAL GARY TALKED ABOUT USING ANTIVIRAL AGENT. NOW, THIS IS A RECENT STUDY FUNDED BY CHINA, THIS IS NOT FUNDED BY US, BUT THIS IS INTERESTING IN THAT THEY LOOKED AT SURGICAL BIOPSIES FOR PEOPLE IN CHINA, LARGE NUMBERS OF PEOPLE, IN THE COUPLE HUNDREDS, AFTER THEY HAD A COVID INFECTION, AND WHAT THEY FOUND IS THAT THERE WAS EVIDENCE OF PERSISTENT RNA FOR SOME OF THE VIRAL GENES, THE N AND THE ORF1A AND ALSO SUBGENOMIC RNA WHICH SUGGESTS THERE'S ACTUALLY REPLICATING VIRUS GOING ON IN THE TISSUES THAT THEY COLLECTED FROM THESE SURGICAL BIOPSIES. AND THIS WAS -- AND THEN IF YOU LOOK A AT HOW THE FINDING OF VIL PERSISTENCE AFFECTS YOUR CHANCE OF LONG COVID, THAT'S WHAT YOU SEE ON THE RIGHT-HAND SIDE, SO VIRAL PERSISTENCE IS THE LOWER BAR IN EACH OF THESE GRAPHS, AND AT TWO MONTHS AND -- ONE MONTH AND TWO MONTHS, IF YOU SEE VIRAL PERSISTENCE, THAT'S A VERY HIGH RISK FACTOR FOR DEVELOPING LONG COVID, IT DROPS DOWN AT FOUR MONTHS, AND IF YOU LOOK AT THE BAR GRAPHS ON THE LEFT AND THE BOTTOM, WHAT YOU SEE IS THAT THE FINDING OF VIRAL PERSISTENCE IS DROPPING OVER TIME. SO IT MAY BE THAT FROM THIS DATA, THAT IT TAKES TIME FOR THE VIRUS -- ACTIVE VIRUS TO ACTUALLY BE CLEARED FROM THE BODY, THAT THIS IS A RISK FACTOR BUT IT'S NOT LIKE A ONE-ON-ONE. IT'S NOT LIKE IF YOU HAVE VIRUS, YOU HAVE LONG COVID. BUT IT'S A RISK FACTOR, AND OVER TIME, YOU LOSE THE CHANCE OF SEEING THE VIRUS, AND THE QUESTION IS THEN HOW DOES THAT AFFECT YOUR RECOVERY. OF INTEREST IS A RECENT PAPER THAT CAME OUT FROM THE V.A. WHICH SHOWED THAT WITH ELECTRONIC HEALTH RECORD DATA, IT'S NOT THE KIND OF DATA THAT WE HAVE OF PATIENTS THAT COME IN TO RECOVER, BUT WHAT THEY SHOW IS IT'S A BIG DROPOFF IN DISABILITY RELATED TO COVID BETWEEN YEAR TWO AND THREE. SO IT DROPPED FROM LIKE 22.9 DAILIES PER 100,000 TO NINE, SO WHAT WE CAN SAY IS I THINK WE'RE LOOKING AT A MOVING TARGET HERE, AND IT WOULD BE GREAT IF EVERYBODY GETS BETTER, THE WORRY IS WE'RE GOING TO HIT A PLATEAU AND WE'LL END UP WITH A LOT OF PEOPLE WHO HAVE THIS MYALGIC ENCEPHALOMYELITIS CHRONIC FATIGUE SYNDROME. THERE WERE A NUMBER OF STUDIES LOOKING AT IMMUNE DYSFUNCTION. DIFFERENCES IN INTERFERON PRODUCTION. AND DIFFERENCE IN MONO NUCLEAR CELLS, PEOPLE WHO HAVE LONG COVID COMPARED TO PEOPLE IN BLUE, MCs WHO MADE A RECOVERY FROM COVID. THERE'S A LOT OF OVERLAP IN SOME OF THESE THINGS BUT CLEARLY ABNORMALITIES HAVE BEEN DISCOVERED AND IN THIS PAPER, IF YOU PUT TOGETHER THE MOST INFORMATIVE MARKERS, YOU GET TO ABOUT A 78% ACCURACY IN DIAGNOSING LONG COVID IN SOMEBODY FROM THESE MARKERS AT A SINGLE POINT IN TIME. IT'S NOT CLEAR THAT THIS WOULD WORK AT FOUR MONTHS AS WELL AS IT WORKS AT ONE MONTH, EIGHT MONTHS OR TWO YEARS. THERE HAS BEEN A LOT OF WORK ON T-CELL ABNORMALITIES IN PEOPLE WITH LONG COVID, AND I THINK A COUPLE OF PAPERS HAVE SEEN THESE KIND OF RESULTS. SEX-SPECIFIC PERTURBATIONS, SO THE IMMUNE SYSTEM IN MALES AND FEMALES ARE DIFFERENT, MANY DIFFERENT ASPECTS, BUT YOU SEE DIFFERENCES IN THE INTRAMURAL STUDY HERE IN LONG COVID, YOU SEE BIG DIFFERENCES BETWEEN MALES AND FEMALES, SO YOU HAVE TO ACTUALLY BREAK THE DATA DOWN AND LOOK AT IT SEPARATELY. EVEN THOUGH IT'S SMALLER Ns, YOU GET MUCH BETTER SIGNALS IF YOU SEPARATE THE DATA INTO MALES AND FEMALES. THERE'S ALSO THIS INTERESTING FINDING, A COUPLE GROUPS, THAT THERE'S A MISCOORDINATION BETWEEN THE IMMUNE REACTION OF B CELLS AND T CELLS. AND MANY OF THE INSTANCES INCLUDING THIS ONE THAT THERE ARE INCREASED NUMBER OF CD8 POSITIVE T CELLS THAT ARE SHOWING SIGNS OF EXHAUSTION, SO THEY HAVE PD-1 MARKERS, TIM3 MARKERS, SO LYMPHOCYTES, T LYMPHOCYTES IN THE EXHAUSTIVE STATE ARE A FOCUS OF ANTICANCER THERAPY BECAUSE THEY PREVENT THE T CELLS, THEY'RE EXHAUSTING T CELLS FROM REACTING AGAINST THE CANCER, AND THEY SECRETE A LOT OF CYTOKINES. THAT'S ONE POSSIBILITY NOW THAT'S RISING UP, TH THAT THIS CONSTANT IMMUNE STIMULATION HAS LED TO EXHAUSTION OF T CELLS AND THAT MAY BE CONTRIBUTING TO THE IMMUNE SYSTEM AND THE PATIENT SYMPTOMS. THERE'S A COUPLE OF PAPERS LOOKING AT THE BRAIN, AND THIS ONE LOOKED IN ANIMAL MODELS FOR PERSISTENT MICROGLIAL REPLICATION AND SPREADING IN BRAIN TISSUE IN MICE MONTHS AFTER THE INFECTION, AND ALSO THAT IS RELATED TO OR COULD BE RELATED TO INCREASED LEVELS OF CCL11, WHICH ACTIVATES MICROGLIA, AND THEY FOUND THIS IN THE SPINAL FLUID OF PEOPLE WHO HAVE LONG COVID COMPARED TO THOSE WHO RECOVERED, SO THESE ARE AGAIN INTERESTING FINDINGS THAT NEED TO BE REPLICATED. WE'VE GOT TO GET SPINAL FLUID, AND IN TERMS OF THE BRAIN, THERE'S ALSO -- ONE OF THE STUDIES ON THE RIGHT WAS FUNDED THROUGH RECOVER LOOKING AT A MARKER, IT'S NOT THE GREATEST MARKER FOR MICROGLIA, BUT IT'S THE BEST WE HAVE NOW AVAILABLE. WHAT THEY'RE FINDING, YOU LOOK AT THE CONTROL VERSUS THE PEOPLE WITH LONG COVID, YOU CAN SEE IN THE RED INCREASED BINDING OF THIS MARKER TO MICRO DPLEE YA IN THE BRAIN, MAYBE REACTIVE ASTROCYTES IN THE BRAIN. ON THE LEFT IS A REPORT OUT OF THE NETHERLANDS WHICH THEY MAY HAVE JUST GOTTEN, THEY JUST PUBLISHED TWO PEOPLE AND THEY SAID BECAUSE THE SIGNAL WAS SO AMAZING, THEY FIGURED THEY COULD JUST PUBLISH IT. BUT YOU CAN SEE ON THE TOP, THIS IS THAT MARKER, RADIO LIGAND MARKER FOR MICROGLIA LIGHTING UP THE BRAIN IN TWO PATIENTS. YOU CAN SEE ON THE BOTTOM IN THE BLUE WHAT THE HEALTHY CONTROL SHOULD LOOK LIKE. MY GUESS IS THEY HAPPENED TO SEE SOME REALLY UNUSUAL CASINGS CASS BECAUSE THE MASS GENERAL GROUP ON THE RIGHT DIDN'T SEE THAT LEVEL OF INTENSITY OF SIGNAL. BUT AGAIN, THESE ARE THE KIND OF THINGS THAT CERTAINLY COULD BE IMPLICATED IN THE LONG COVID SITUATION. THERE'S ALSO A PAPER OUT OF IRELAND WHERE THEY LOOKED AT BRAIN BARRIER BREAKDOWN. AS YOU KNOW COVID WAS REALLY NASTY ON THE ENDOTHELIAL CELLS, AND THIS GROUP ACTUALLY -- THEY GIVE A DYE AND THEY SCAN THE BRAIN WITH MRI SCAN, THEY SEE THE DYE GO OUT INTO THE BRAIN AND FIND THAT THERE'S REALLY A LEAKAGE OF THE BLOOD BRAIN BARRIER IN PEOPLE WITH LONG COVID WHO HAVE COGNITIVE IMPAIRMENT, NOT THOSE WHO HAVE LONG COVID WITHOUT COGNITIVE IMPAIRMENT. AGAIN, THIS NEEDS TO BE REPLICATED. THE SIGNAL-TO-NOISE IS ACTUALLY PRETTY LOW IN THIS ONE SO IT REALLY DOES NEED TO BE REPLICATED. SO I THINK WE HAVE A LOT OF CULPRITS OUT THERE, NOW WE'VE GOT TO FIGURE OUT WHO DO WE ARREST AND PUT IN JAIL AND HOPEFULLY MAKE THIS -- MAKE PEOPLE BETTER QUICKER. THANKS. GARY? >> HOPEFULLY, WALTER, WE'RE NOT GOING TO JAIL AS PART OF THAT. SO MY TASK IS TO DESCRIBE THE CLINICAL TRIAL PLATFORM COMPONENT OF RECOVER. AND THE DEVELOPMENT OF NOT ONLY THE INFRASTRUCTURE, BUT AN APPROACH TO DEVELOPING THOSE PROTOCOLS THAT CAN TEST SOME OF THOSE HYPOTHESES. ONE OF THE CHALLENGES, OF COURSE, IN THE VERY BEGINNING THAT GAVE US ALL A SENSE OF APPROACHING THIS WITH GREAT HUMILITY HAS BEEN ALLUDED TO BY MY TWO COLLEAGUES AS HUGH MENTIONED, TONY WAS AN EARLY OBSERVER OF THE NOTION OF THAT OVERLAP BETWEEN ME/CFS AND NIAID AND NINDS HAVE BEEN STUDYING ME/CFS FOR MANY, MANY YEARS, DECADES OR MORE, AND YET WE DON'T HAVE FDA-APPROVED DRUGS FOR THAT. SO THERE'S NOT A LOT OF SUCCESS IN THIS POST INFECTION CHRONIC CONDITION SPACE. AND IN PARTICULAR, WHERE IT'S SO PLEIOTROPIC AND HETEROGENEOUS THAT EVEN A CASE DEFINITION WAS LESS THAN CLEAR. SIMILARLY, THE REGULATORY PATHWAY FOR AGENTS THAT WOULD AFFECT THIS DISORDER WAS UNCL UNCLEAR. QUITE FRANKLY, THE FDA WAS CHALLENGED BY DEVELOPING A REGULATORY PATHWAY THAT WOULD INCLUDE BIOLOGICS, SMALL MOLECULES, DEVICES FOR A CONDITION THAT STILL DIDN'T HAVE A CASE DEFINITION, IT WAS AFFECTING THE ENTIRE BODY. IT WASN'T ONE LITTLE DIVISION OF FDA THAT WAS REALLY SET UP FOR THIS SORT OF THING. SO THIS PRESENTED A NUMBER OF DIFFERENT CHALLENGES, NOT THE LEAST OF WHICH WAS ALSO GETTING A CONSENSUS ON THE END POINTS THAT WOULD BE IMPORTANT FOR AN APPROVAL BE OF NOT ONLY SAFETY BUT EFFICACY. SO IN SETTING UP THE NOTION OF TREATING THESE FOLKS, THERE WERE A NUMBER OF CHALLENGES TO OVERCOME. SIMILARLY, WE RECOGNIZED THAT WE WERE IN THE MIDST OF ACUTE COVID, AND THE PANDEMIC, AND THE NOTION THAT ONE OF THE LESSONS LEARNED IN THAT PERIOD WAS D DOING -- LETTING A THOUSAND FLOWEBLOOM, IF YOU WILL, WITH AT OF SMALL STUDIES THAT CROPPED UP DURING COVID, MANY OF WHICH DID NOT HAVE THE COMMON SHARED DATA ELEMENTS OR END POINT OR INCLUSION TRY TIER YA AND CRITEY SLOWED AND GUMMED UP THE WORKS IN A LOT OF OUR ACUTE COVID INTERVENTIONS AS PART OF THE ACTIVE PLATFORM. SO WE CLEARLY DIDN'T WANT TO DO THAT FOR LONG COVID, SO IT WAS REALLY IMPORTANT TO HAVE A PROCESS WHEREBY WE GOT ALL THESE DIFFERENT DISCIPLINES TOGETHER. LIKE THE THREE INSTITUTES HERE, BECAUSE IT COVERED SO MANY ORGAN SYSTEMS, NEARLY EVERY ORGAN SYSTEM, AND THAT WE WOULD NEED CROSS DISCIPLINARY TEAMS TO DEVELOP THESE PROTOCOLS. SO THE APPROACH IN MANY WAYS WAS VERY INCLUSIVE OF THAT INCLUDING ALL THE VARIOUS STAKEHOLDERS, PERHAPS THE MOST IMPORTANT OF WHICH WERE PATIENTS AND FRONT LINE PROVIDERS WHO PROVIDE GREAT EXPERTISE WITH THEIR LIVED EXPERIENCE, AND WE WERE SURE TO ALSO INCLUDE NOT ONLY OUR COLLEAGUES AT FDA AND OTHER AGENCIES AN IN AN ALL OF GOVERNT APPROACH, BUT ALSO THE PRIVATE SECTOR, A KEY PART IN THOSE EARLY DAYS WAS TO LITERALLY DO A LISTENING TOUR WHERE WE ENGAGED NEARLY TWO DOZEN COMPANIES AS WE EXPLORED THEIR INTEREST AND SHARED INTEREST IN PURSUING THERAPEUTICS TO ADDRESS THE SUFFERING OF THESE PATIENTS AND THE INCREDIBLE UNMET NEED THAT WE ARE OBVIOUSLY APPROACHING WITH MILLIONS OF PATIENTS BEING AFFECTED. SO THIS ALSO WAS TO BE INFORMED BY THE PATHOBIOLOGY STUDIES, SOME OF WHICH WALTER ALLUDED TO, AND IN ADDITION, AS WE WERE BUILDING THESE COHORTS, AND LEARNING THAT CLINICAL SPECTRUM, THAT WAS GIVING US INSIGHTS AS TO HOW TO SHAPE AND DEVELOP THE CLINICAL TRIAL PLATFORM. SO ALL THESE DIFFERENT PIECES WERE COMING TOGETHER AS WE TRIED TO ESTABLISH AN ADAPTIVE SET OF MASTER PROTOCOLS THAT WOULD ENABLE US TO HAVE -- WITH EFFICIENCY AND CONSISTENCY, ROBUST SET OF CLINICAL TRIALS THAT WE COULD ASSESS AND FIND OUT RELATIVELY EFFICIENTLY WHAT'S WORKING, WHAT'S NOT, AND HAVE A MEANS OF TESTING A VARIETY OF INTERVENTIONS. AGAIN, WITH PATIENTS ACTUALLY PROVIDING A LOT OF THAT EARLY INPUT AS TO HOW WE WOULD GO WITHOUT IT, INCLUDING AN UNDERSTANDING OF WHICH SYMPTOMS WERE MOST IMPORTANT TO THEM IN WHICH RELIEF WOULD MAKE THE GREATEST IMPACT ON THEIR LIVES. AND THAT REALLY SHAPED THE STRUCTURE OF THE FIVE MASTER PLATFORMS THAT AGAIN WAS INFO INFORMED BY THE CLUSTERING SYMPTOMS THAT WE DISCERN FROM THE OBSERVATIONAL STUDIES AND THAT REALLY SHAPED THESE FIVE PLATFORMS BASED ON THOSE SYMPTOM CLUSTERS PRIORITIZED BY THE PATIENTS, AND AGAIN, PATIENTS WERE PART OF THE PROTOCOL DEVELOPMENT AS WELL OF THESE DIFFERENT PLATFORMS. THE FIRST ONE, VITAL, RELATED TO THE HYPOTHESES AROUND VIRAL PERSISTENT ANTIGEN AND POTENTIAL REPLICATION AS WELL AS IMMUNE DYSREGULATION. AND THE FIRST INTERVENTION IS PAXLOVID THAT RELATES TO THAT. SIMILARLY, NEURO AGAIN WAS RELATED TO PATIENTS' COMPLAINTS ABOUT THE BRAIN FOG AND COGNITIVE DYSFUNCTION. AUTO, RELATED TO THE DISTURBANCES OF THE AUTONOMIC SYSTESYSTEM, TH CLEARLY THE SLEP DISORDERS WAS ANOTHER ELEMENT. THAT PATIENTS IDENTIFIED AND WHICH WAS CLEARLY PROBLEMATIC, BOTH EXCESSIVE SLEEP AND DISRUPTED SLEEP AS MAJOR PROBLEMS, AND THEN FINALLY, THE ENERGIZE PLATFORM THAT RELATED TO THE EXERCISE AND TOLERANCE, POST EXERTIONAL MALAISE AND FATIGUE. AND SO THESE FIVE ADAPTIVE PLATFORMS REALLY INVOLVED EIGHT CLINICAL TRIALS. WHEN YOU LOOK AT THE SUBGROUPS. AND 13 INTERVENTIONS WERE DEVELOPED AS PART OF THE PROTOCOL DEVELOPMENT PROCESS. ALL OF WHICH HAD SHARED CLINICAL END POINTS AND COMMON DATA ELEMENTS AND INSTRUMENTS THAT WE NOW CAN EXERCISE LITERALLY AS PART OF THESE VARIOUS PLATFORMS, AND INDEED, EACH CAN INFORM THE OTHER, CERTAINLY THE PLACEBO GROUPS, IN THAT REGARD. SO MANY WAYS WE REALLY HAVE NOW ESTABLISHED A PLATFORM WITH OUR FDA COLLEAGUES, A REGULATORY PATHWAY WHERE THESE SORTS OF END POINTS AND INCLUSIONS AND CASE DEFINITIONS NOW PROVIDE A FRAMEWORK THAT WE ANTICIPATE WILL ENHANCE OTHER REGISTRATION TRIALS AFTER THE PAXLOVID TRIAL. THIS JUST PROVIDES A LITTLE BIT MORE DETAIL IN WHICH THE VARIOUS INTERVENTIONS ARE ENUMERATED. I WON'T GO THROUGH THAT IN MUCH DETAIL EXCEPT THAT YOU CAN SEE NOW THE SPECIFIC AGENTS THAT ARE ON EACH PLATFORM WITH THE NOTION THAT THIS IS OUR FIRST WAVE OF 13 INTERVENTIONS, AND JUST LIKE EVERYTHING ELSE, WE'RE LEARNING AS WE GO AND ADAPTING IN THAT WAY, AS WALTER ALLUDED TO, WE ANTICIPATE THAT THE ONGOING INVESTMENTS IN PATHOBIOLOGY STUDIES THAT ARE ALSO UNDERWAY IN RECOVER WILL CONTINUE TO PROVIDE MORE MECHANISTIC INSIGHTS THAT WILL FURTHER IDENTIFY TARGETS AND PATHWAYS THAT WILL INFORM THE NEXT WAVE OF INTERVENTIONS. AND WE'RE POISED TO DO SO NOW THAT WE HAVE AN INFUSION OF NEW RESOURCES FROM HHS, 515 MILLION THAT WE ANTICIPATE WILL BE TARGETED WITH A MAJOR EMPHASIS ON THOSE SUBSEQUENT WAVES OF CLINICAL TRIALS. SO JUST TO CONCLUDE, I THINK WHAT WE'VE TRIED TO BRIEFLY DESCRIBE COLLECTIVELY WITH THE THREE INSTITUTES THAT HAVE BEEN CHARGED TO LEAD THIS AS PART OF A TRANS-NIH EFFORT IS THAT WE'VE MADE IMPORTANT PROGRESS CERTAINLY IN ESTABLISHING A VERY ROBUST INFRASTRUCTURE OF COHORT STUDIES, NOT ONLY AT THE ELECTRONIC HEALTH RECORD TO SEE THINGS AT SCALE, 60 MILLION RECORDS THAT PROVIDED DOZENS AND DOZENS OF PUBLICATIONS THAT HAVE PROVIDED INSIGHT INTO INCIDENCE, PREVALENCE, RISK FACTORS, PARTICULAR SUBGROUPS, NEW ONSET DISEASES, REALLY CHARACTERIZING AT A POPULATION SCALE LEVEL WHAT LONG COVID IS, AND HAS REALLY DRIVEN THE FIELD IN THAT REGARD, ALONGSIDE OTHER DATASET LIKE THE VA, BUT SIMILARLY ALSO THE 60,000 INDIVIDUALS WHO WERE CAPTURED IN COMMUNITY-BASED COHORT LIKE IN CHILDREN, ABCD AND OTHERS, IN ADUR ADULT COHORS WELL AS THOSE WHO ENROLLED, 30,000 AS WAS MENTIONED OF CHILDREN, ADULTS, PREGNANT PEOPLE, THE AUTOPSY COHORTS, REALLY A COMPREHENSIVE AND VERY ROBUST DISCOVERY INFRASTRUCTURE TO CHARACTERIZE LONG COVID. AND NOW THOSE ADDITIONAL CHARACTERIZATION IS PROCEEDING AT PACE IN WHICH NOT ONLY ARE WE CHARACTERIZING BASIC CLINICAL PARAMETERS OF SYMPTOMS AND PULMONARY FUNCTION AND VARIOUS PARAMETERS LIKE THAT, BUT ALSO AS WALTER ALLUDED TO, WERE INCREASINGLY SOPHISTICATED AND TO A CERTAIN EXTENT INVASIVE ASSESSMENTS AT BIOPSIES AND VARIOUS FORMS OF SCANS THAT WE THINK WE'LL BE ABLE TO FURTHER DEEPLY PHENOTYPE THESE LONG COVID PATIENTS. SIMILARLY, WE'RE EXCITED ABOUT THE INVESTMENTS BEING MADE IN PATHOBIOLOGY, IN WHICH AS WALTER ALLUDED TO, WE'RE GETTING A FURTHER AND DEEPER UNDERSTANDING WITH IN DEPTH IMMUNOPHENOTYPING AND CHARACTERIZATION. SOME OF THE MECHANISTIC DRIVERS OF THESE SICTS THAT, AGAIN, SHOULD BEAR FRUIT IN DESCRIBING POTENTIAL NEW TARGETS FOR THERAPY. SIMILARLY WE'RE LAUNCHING REALLY A SYSTEMS BIOLOGY STRATEGY THAT WILL TAKE A MULTI-OMIC APPROACH TO UNDERSTANDING THIS IN EVEN GREATER DETAIL AT THE MOLECULAR LEVEL THROUGH THIS ENTIRE COHORT. SO NOT ONLY VALIDATING SOME OF THOSE SMALLER OBSERVATIONS BUT GOING AT SCALE TO FULLY CHARACTERIZE THE PROTEOMICS, TRANSCRIPTOMICS, EPIGENOMICS, ET CETERA, THAT IS HAPPENING IN THESE PATIENTS AS THEY BOTH RECOVER AND/OR HAVE PERSISTENT SYMPTOMS, AND ALL OF THAT IN A COMPLEMENTARY WAY DRIVING WHERE WE ARE WITH OUR CLINICAL TRIALS HOPEFULLY INFORMING THE NEXT WAVE THAT WE'RE POISED TO TEE UP MOVING FORWARD. IN THAT REGARD, A KEY PART OF MOVING FORWARD IS THE ONGOING RELEASE OF THE DATA. NOW THAT WE'VE ESTABLISHED THIS INCREDIBLE PLATFORM, THE LARGEST, MOST DIVERSE AND DEEPLY CHARACTERIZED COHORTS OF LONG COVID WE THINK EXIST IN THE WORLD, AS WELL AS A PLATFORM WITH EIGHT TRIALS AND 13 INTERVENTIONS THAT, AGAIN, IS NOT MATCHED BY ANY OTHER PROGRAM ANYWHERE IN THE WORLD, THAT ALL THIS DATA WILL BECOME AVAILABLE OR IS AVAILABLE TO THE BROADER EXTRAMURAL COMMUNITY. INDEED THE FIRST 12,000 INDIVIDUALS IN THE ADULT DATASET WAS PUT IN A CLOUD-BASED DATA RESOURCE, BIODATA CATALYST, IN WHICH THAT DATA IS NOW OPEN AT AN INDIVIDUAL PARTICIPANT LEVEL AND DE-IDENTIFIED AND CONTROLLED ACCESS WAY FOR INVESTIGATORS IN THE BROAD COMMUNITY. WE'RE ALSO ANTICIPATING, NOW THAT WE'VE SECURED THE $515 MILLION FROM HHS, A WHOLE NEW ROUND OF NOFOs SUMP THAT THERE WILL BE AWARD OPPORTUNITIES, AGAIN, TO THE BROADER COMMUNITY TO FURTHER MINE THIS INCREDIBLE DATA RESOURCE. SO WE'RE VERY EXCITED NOW THAT THIS INCREDIBLE INFRASTRUCTURE HAS BEEN ESTABLISHED, THAT WE'LL BE IN A PHASE OF RAPID DISCOVERY THAT WE THINK WILL FUEL THE NEXT WAVE OF CLINICAL TRIALS WITH INTERVENTIONS THAT ARE ROBUSTLY DESIGNED, AND ARE POISED TO HAVE AN IMPACT IN A WAY TO TRY TO ADDRESS THE SUFFERING OF THESE PATIENTS AS QUICKLY AS POSSIBLE. WITH THAT, THANK YOU ALL FOUR YFORYOUR ATTENTION, MY COLLEAGUS WELL. >> OKAY. QUESTIONS FOR THE TEAM? >> GARY, SINCE THE TRIALS WERE STAGGERED, THE ONE THAT BEGAN FIRST PRESUMABLY WILL READ OUT FIRST, DO YOU HAVE A GUESS TAMENT GUESSTIMATEABOUT WHEN YOG READOUTS FROM THE PAXLOVID TRIALS? >> WELL, IT IS MAKING EXCELLENT PROGRESS. IT'S ACTUALLY MOVING FAIRLY BRISKLY IN TERMS OF HITTING ITS ACCRUAL AND ENROLLMENT TARGETS. AS I'M SURE YOU'RE YOU'RE AWARS ONE THING TO ACCRUE AND HIT THE TARGET, BUT AN IMPORTANT ASPECT OF THESE STUDIES AS WAS ALLUDED TO HAVE TRACKING THE RESPONSE AND SYMPTOMS, AND SO AS WALTER INDICATED, PARTICULARLY FOR MANY OF THESE PATIENTS, THAT CLINICAL COURSE MAY WAX AND WANE, SO THERE REALLY OUGHT TO BE FAIRLY GOOD FOLLOW-UP TO BE SURE THAT A GIVEN INTERVENTION, WHICH IN THE CASE OF PAXLOVID, WAS EITHER 15 DAYS OR 25 DAYS OF THERAPY, MUCH LONGER THAN THE STANDARD SORT OF FIVE-DAY COURSE GIVEN IN ACUTE COVID, AND TO BE SURE THAT THAT HAS A LASTING DURATION OF RESPONSE. SO NEST WHY IT SHOULDN'T BE IF YOU ENROLLED THEM, WHERE'S THE ANSWER. IT A MATTER OF BEING SURE THAT WHAT WE'RE SEEING IN FOLLOW HAD, SO THAT WILL TAKE US CLEARLY INTO 2025 TO START TO SEE THAT. WE HAVE DATA SAFETY MONITORING BOARDS THAT ARE ALWAYS TRACKING THESE THINGS TO SEE IF WE ARE SEEING A SIGNAL OR NOT, AND I THINK IT WOULD BE BEST TO JUST SAY WE'RE BEING VIGILANT FOR THOSE END POINTS AS WELL AS THE FDA AND OUR PARTNER AT THE ADVISOR REGARDING THAT FINAL READOUT. >> HOWARD. >> GREAT. SO THANK YOU FOR ALL THE PRESENTERS FOR HAVING THIS REALLY IMPORTANT AND IMPRESSIVE ARRAY OF EFFORTS AT NIH TO DEAL WITH THIS IMPORTANT PROBLEM. I THINK THE SCOPE OF THE CLINICAL TRIALS ARE AMAZING. CAN YOU SAY MORE ABOUT THE DIVISION OF RESOURCES TO TRIALS WHICH I ASSUME TAKE MUCH MORE RESOURCES THAN PATHOBIOLOGY BECAUSE AS YOU POINTED OUT, IT'S STILL NOT VERY CLEAR, WE HAVE TO MANY CANDIDATE MECHANISMS AND IT'S UNCLEAR WHAT IS REALLY GOING ON, AND WHAT IS THE PROCESS IN THE TRIALS TO CONTINUE TO BRING IN ALL THESE MECHANISTIC STUDIES TO GET INSIGHTS INTO WHAT A -- IS ACCOMPLISHING -- SYMPTOMOLOGIC END POINTS. >> OH, BOY. HOWARD, I CAN TAKE THIS ONE BECAUSE YOU JUST HIT A CENTRAL ISSUE THAT I WAS DANCING AROUND WHEN I WAS GIVING THE INTRODUCTION. YEAH, THERE'S JUST A WEALTH OF INFORMATION HERE. THE INITIAL PATHOPHYSIOLOGY STUDIES, MANY DIFFERENT DIRECTIONS TO GO THERE. I MEAN, YOU KNOW, I COULD SIT AND MAKE A LIST OF 30 DIFFERENT AT LEAST POTENTIAL WAYS, POTENTIAL THERAPEUTICS TO PURSUE. AND I DON'T THINK -- THE HONEST ANSWER IS, WE DON'T HAVE AN ANSWER FOR YOU YET BECAUSE WHAT IS GOING TO HAPPEN NOW IS A VERY RAPID AND INTENSE PERIOD OF PLANNING FOR HOW WE STRATEGIZE TO USE THE NEW RESOURCES WE HAVE RECEIVED. WE RECEIVED $515 MILLION NOW TO MOVE FORWARD. THE FOCUS OF THAT IS GOING TO BE TO PRODUCE TREATMENTS FOR THIS DISEASE, BUT EXACTLY WHAT'S THE BEST STRATEGY TO ACHIEVE THAT IS GOING TO BE SOME INTENSE FOCUS OVER THE NEXT COUPLE MONTHS. YOU KNOW, I MEAN, DID I SAY THIS RIGHT, GUYS? AND SO WE'RE TAKING THIS ACTIVITY, THIS INTENSE PLANNING ACTIVITY INTO THE OFFICE OF THE DIRECT, TO AND WE'RE PULLING OUT ALL THE STOPS TO COME UP WITH THE SMARTEST POSSIBLE PLAN. KNOWING WHAT WE KNOW TODAY. AND THE BEST POSSIBLE WAY TO USE THIS NEW INFUSION OF MONEY THAT WE'VE GOTTEN. AS I'M SURE YOU KNOW, IT'S CHALLENGING, WE WANT TO KEEP THE COHORTS GOING BECAUSE WE'RE GOING TO GET SO MUCH MORE IMPORTANT NATURAL HISTORY INFORMATION OUT OF THOSE, SO WE HAVE TO PUT SOME FUNDING INTO THE COHORTS, WE'D LIKE TO SEE THE BASIC SCIENCE CONTINUE, OF COURSE, BUT WE ALSO KNOW, WE REALLY DO HAVE A NUMBER OF SOLID HYPOTHESES NOW THAT CAN BE PURSUED WITH CLINICAL TRIALS. SO LET ME TURN IT BACK OVER TO THE EXPERT. ANY OTHER -- ADD ANYTHING TO THAT? >> I THINK WHAT WE DID IN THE BEGINNING WAS WE HAD A CALL FOR IDEAS AND PEOPLE SUBMITTED IDEAS AND THEN WE HAD THEM REVIEWED AND WE PICKED THE ONES TO GO IN, AND I THINK AS GARY MENTIONED SOME OF THE TRIALS ARE GOING TO BE ENDING UP IN LATE 24, EARLY 25, SO IT'S A GREAT TIME TO THINK ABOUT WHAT YOU WOULD WANT TO TRY NEXT. THE HOPE IS THAT -- THE HOPE FROM THE BEGINNING WAS THAT WE'D HAVE SOME BIOMARKER TO GO AFTER. TRYING TO TREAT A DISEASE WITHOUT KNOWING WHAT PATHOLOGIC MECHANISM YOU'RE AFTER AND HOW YOU KNOW IF YOU ENGAGE THAT TARGET, THAT'S TREACHEROUS. IT LIKE JUST SHOOTING IN THE DARK. BUT HOPEFULLY NOW, WE CAN MAKE SOME MORE KIND OF RATIONAL DECISIONS IN THAT SPACE. PLUS THE OTHER THING, IT'S BEEN AROUND, WE TALK TO A LOT OF PRIMARY CARE DOCS WHO ARE TAKING CARE OF THESE FOLKS, THEY CLAIM THERE ARE SOME THINGS THEY THINK ARE WORKING. WE'VE GOT TO TAKE THAT SERIOUSLY. A LOT OF MEDICATIONS WE USE IN PSYCHIATRY AND NEUROLOGY, THEY WEREN'T RATIONALLY DESIGNED, THEY WERE JUST KIND OF SERENDIPITOUSLY DISCOVERED SO WE HAVE TO KEEP OUR EYES AND EARS OPEN AND REFRESH. >> THOSE ARE GOOD POINTS, AND MY -- BIOBANKING THESE SAMPLES FOR THESE TRIALS THAT WILL POTENTIALLY OPEN FOR FUTURE MECHANISTIC INVESTIGATION. >> I DON'T WANT TO BE MISQUOTED ON NUMBERS OF VIALS BUT IT'S TENS OF MILLIONS OF VIALS AT THIS POINT THAT ARE IN OUR BIOREPOSITORY FOR RECOVER, SO THAT'S NOT ONLY THE OBSERVATIONAL STUDY BEING DONE SERIALLY IF PEOPLE HOPEFULLY CONTINUE TO RECOVER OR NOT, IT ALSO EMBEDDED WITHIN A NUMBER OF THE CLINICAL TRIALS AS WELL. SO WE THINK WE HAVE A FAIRLY ROBUST INFRASTRUCTURE FOR ONGOING INVESTIGATION BY THE BROAD COMMUNITY, NOT ONLY THOSE WHO ARE CURRENTLY RECOVERING INVESTIGATORS BUT THOSE WHO CAN HAVE HYPOTHESES AND, AGAIN, LEVERAGE THE DATA RESOURCE THAT'S OUT THERE THAT HAS THE PATIENTS AS WELL AS THE BIOSPECIMENS AS A POWERFUL LINKAGE THAT WILL -- AND COMPREHENSIVELY PHENOTYPE. SO WE THINK IT WILL BE A RICH DATA RESOURCE FOR THIS PARTICULARLY POST INFECTION CHRONIC CONDITION. >> THANK YOU. >> THANK YOU VERY MUCH FOR THE PRESENTATION AND THIS WEALTH OF WORK. IT'S AMAZING. I'M WONDERING, WHAT ARE THE LESSONS LEARNED FROM ME CSF? I MEAN, WE'VE HAD THAT FOR A LONG TIME, AND ARE THERE LESSONS LEARNED THAT SORT OF MOVE US TO TRYING TO IDENTIFY SPECIFIC INTERVENTIONS VERSUS SYMPTOMATIC INTERVENTIONS? I'M JUST CURIOUS ABOUT THE HISTORY OF ME CSF AND WHAT THAT TEACHES US. >> WELL, I THINK AS GARY SAID, THERE'S NO APPROVED THERAPY FOR ME CSF. IT'S TOUGH BECAUSE PEOPLE WAX AND WANE, SO SOME PHYSICIANS, SOME PATIENTS BELIEVE THAT CERTAIN THINGS HELP THEM, BUT THEY'VE NEVER BEEN DEMONSTRATED IN A RANDOMIZED CLINICAL TRIAL. SO THERE MIGHT BE THINGS THERE THAT WE NEED RANDOMIZED CLINICAL TRIALS TO DO. I THINK THE LESSON FROM ME/CFS WAS THAT YOU'RE NOT GOING TO FIX THE PROBLEM WITH A LOT OF SMALL STUDIES, THAT YOU REALLY NEED TO COLLECT A REALLY WELL PHENOTYPED COHORT, COLLECT THE SAMPLES, AND GO AFTER IT IN A VERY SYSTEMATIC FASHION. WE JUST CAME FROM -- WE HAVE A CONSORTIUM WITHIN NIAID FOR ME/CFS RESEARCH, WE JUST CAME BACK FROM MEETINGS THERE. AGAIN, AS I DEMONSTRATED HERE, THERE'S LOTS OF FINDINGS BUT ACTUALLY WHICH ONE YOU PUT YOUR MONEY ON IS DIFFICULT TO KNOW. SO I THINK THAT THE RECOVER WAS REALLY INFORMED BY ME/CFS RESEARCH. >> AND I'LL ADD ONE THING TO THAT. YOU KNOW, I THINK ANOTHER LESSON LEARNED FROM ME/CFS IS THAT WE NEED TO DO BETTER. WE REALLY NEED TO DO BETTER FOR PEOPLE WITH THESE CHRONIC POST INFECTIOUS SYMPTOMS. I THINK THE COMMUNITY OF PEOPLE SUFFERING FROM THAT DISEASE FEEL LIKE THERE HASN'T BEEN AN URGENCY TOWARD TRULY TRYING TO SOLVE THAT PROBLEM, AND SO NOW THAT WE HAVE THIS OPPORTUNITY, WE DON'T WANT TO WASTE THE OPPORTUNITY TO CLUP THEM AND MAKE SURE THAT WE UNDERSTAND HOW TO SOLVE THIS FOR THAT ENTIRE COMMUNITY. I THINK THAT'S REALLY CRITICAL. >> JUST MAYBE TO UNDERSCORE THAT, I THINK THAT'S ONE OF THE OPPORTUNITIES OF THE ADDITIONAL FUNDING WE HAVE BEEN PROVIDED WITH, IS TO ENGAGE IN SOME OF THOSE MORE COMPARATIVE STUDIES. AS WALTER IS ALLUDING TO, AND HUGH AS WELL, UNDERSTANDING THOSE OVERLAPS, AND IT MAY BE AN OPPORTUNITY NOT ONLY TO TAKE WHAT WE'VE LEARNED IN LONG COVID, BUT HOPEFULLY INFORM THOSE OTHER POST INFECTION CHRONIC CONDITIONS LIKE ME/CFS. I'M. THAT'S AN OPPORTUNITY WE CAN DO OVER THESE NEXT FEW YEARS WITH THIS ADDITIONAL CAPITAL. >> SORRY, ONE OTHER COMMENT THAT THE PATIENT WITH ME/CFS ARE INCREDIBLY FRUSTRATED BY THE LACK OF INTEREST BY PHYSICIANS IN TAKING CARE OF THEM. SO FOR YEARS, THEY HAVE BEEN FIGHTING A PERCEPTION THAT PEOPLE DON'T THINK THEY HAVE ANYTHING WRONG WITH THEM. AND IT'S IN THEIR HEAD, QUOTE-UNQUOTE. SO HOPEFULLY LONG COVID HAS GOTTEN RID OF THAT. AFTER WHAT WE'VE SEEN IN THE LONG COVID FROM THE COVID PANDEMIC, THIS IS CLEARLY AN IMMUNE DISORDER, THERE'S NO QUESTION ABOUT IT. SO I THINK WE KIND OF GET OVER THAT. I THINK IN THE ME/CFS COMMUNITY, WE DON'T HAVE THE WORKFORCE. WE'RE TALKING ABOUT PAIN RESEARCH BEING TOUGH. ME/CFS -- BUT NOW WE HAVE HUNDREDS OF PEOPLE WORKING ON LONG COVID. THE HOPE IS THAT THEY SEE THIS DISEASE AS SOMETHING THAT THEY CAN PURSUE AS A SCIENTIFIC CAREER. THAT WOULD BE GREAT FOR LONG COVID, ME/CFS, WHATEVER THE NEXT INFECTION POST, YOU KNOW, NASSEM CALLED IT -- POST CHRONIC -- WHAT WAS THAT NASSEM TITLE? >> MONICA, JUST TO MENTION THAT AS WE DISCUSSED BEFORE, WE DO HOPE TO HAVE A MAJOR INVESTIGATOR AND PATIENT PARTICIPATION MEETING BY EARLY IN THE FALL TO REVIEW DIRECTIONS GOING FORWARD. >> WONDERFUL. ALL RIGHT. THANK YOU SO MUCH. YES, ATUL. >> I THINK THERE'S STILL A LOT OF SKEPTICISM ABOUT LONG COVID. IT'S A TRAGEDY ACTUALLY THAT THERE'S SKEPTICISM, BUT I SENSE THERE'S STILL SKEPTICISM. BUT THERE'S ALSO SKEPTICISM ABOUT RECOVER IT SO THE, NOT THE ARTICLES. MONICA, YOU'RE MENTIONING YOU PUT OFFICE OF THE DIRECTOR INTO THIS. IS THERE A NEW OVER SIGHT OF RECOVER THROUGH THE OFFICE OF THE DIRECTOR, OF THE WHOLE PROJECT? I THINK A LOT OF -- AGAIN, JUST SPEAKING PERHAPS OUT OF TURN, THERE'S MAYBE A LITTLE BIT OF A REQUEST FOR MORE TRANSPARENCY AS TO HOW THE FUNDS ARE GETTING SPENT, I THINK IT'S FAIR TO SAY. IS THERE A NEW OVERSIGHT, IS THAT WHAT YOU MEANT BY BRINGING OD INTO THIS? >> TRANSPARENCY IS FAIR. I MEAN, WE REALLY NEED TO BE TRANSPARENT ABOUT HOW WE'RE SPENDING OUR FUNDING. I THINK I CAN VERY, VERY EASILY DEFEND WHAT RECOVER HAS DONE. I MEAN, AGAIN, YOU JUST SAW IT, RIGHT? I MEAN, THESE ENORMOUS COHORTS, UNDERSTANDING OF THIS DISEASE, AND YOU KNOW, I'VE ALSO SEEN THE LIST OF REALLY AMAZING MANUSCRIPTS THAT ARE GOING TO START TO EMERGE RIGHT OVER THIS SUMMER FINALLY. I THINK PEOPLE WILL START FEELING MUCH BETTER ABOUT RECOVER, ITS FIRST WAVE ONCE THE MANUSCRIPTS REALLY START FLOWING, WHICH THEY ARE DEFINITELY COMING. AND I THINK THE OTHER LESSON IS, NOW THE INFRASTRUCTURE HAS BEEN BUILT, AND IT IS AN INFRASTRUCTURE ON A SCALE THAT HAS NEVER HAPPENED BEFORE IN RESEARCH, EVER. SO I CAN CERTAINLY DEFEND ALL OF THAT. THE REASON FOR MOVING IT INTO THE OD IS TO GET EVERYONE TOGETHER TO NOW TAKE A LOOK AT EVERYTHING WE'VE LEARNED AND THEN COME UP WITH A STRATEGY FOR MOVING FORWARD. THAT -- RECOVER IS NOT MOVING INTO THE OD. I MISSPOKE. RECOVER IS DEFINITELY NOT MOVING INTO THE OD. WHAT'S MOVING INTO THE OD IS THIS BIG PLANNING ACTIVITY. AND WHY? WHY DID I THINK THAT NEEDED TO LAND IN THE OD? BECAUSE OF HOW CRITICALLY IMPORTANT THIS IS AS AN INITIATIVE THAT IS DOING THINGS WE'VE NEVER, EVER DONE BEFORE, AND WITH THE ABILITY TO KIND OF ENGAGE IN EVEN BROADER -- BROADER COMMUNITY. SO ONLY PLANNING. AND THEN WE'LL MOVE FORWARD WITH THE NEXT WAVE OF RESEARCH COMING OUT OF WHAT WE'VE LEARNED WITH THE FIRST WAVE. >> THANK YOU. >> [INAUDIBLE] >> WELL, YOU KNOW, THIS IS A BIG CENTRAL PLANNING ACTIVITY. AND I WANT TO SIGNAL TO THE COMMUNITY, I THINK THAT'S ALSO REALLY IMPORTANT, WE'RE SIGNALING TO THE COMMUNITY THAT WE ARE GOING TO, YOU KNOW -- WE'VE BUILT AN AMAZING INFRASTRUCTURE AND NOW WE'RE GOING TO SIT DOWN AND TAKE A VERY DEEP LOOK AT WHAT WE'VE LEARNED AND THEN COME UP WITH A PLAN TO GO FORWARD AND BE VERY TRANSPARENT ABOUT THAT AND BE VERY CLEAR ABOUT THAT, AND FRANKLY, WE CAN BE THAT WAY NOW BECAUSE WE'VE LEARNED SO MUCH. OTHER QUESTIONS? OKAY. MAYBE WE'LL GO AHEAD AND MOVE ON. I THINK THAT'S ME. OKAY. >> THANK YOU, EVERYBODY. MOVING FORWARD. WE'RE GOING TO TALK ABOUT THE NATIONAL LIBRARY OF MEDICINE AND SOME THOUGHTS THAT WE HAVE ABOUT A NEW VISION FOR THIS REALLY IMPORTANT COMPONENT OF NIH. WHAT IS THE NLM, WHAT'S ITS MISSION OVERALL? BASICALLY ACCELERATING DISCOVERY AND DATA-POWERED HEALTH. THESE COME FROM SOME WORK THAT WAS DONE BY DR. PATTI BRENNAN AND THE REST OF THE TEAM AT NLM TO REALLY -- TO ORGANIZE THE RESEARCH EFFORTS IN THE LATEST STRATEGIC PLAN FOR NLM AND REALLY TO DEFINE A VISION FOR THE FUTURE, TO ACCELERATE DISCOVERY AND ADVANCE HEALTH THROUGH DATA-DRIVEN RESEARCH, REACH MORE PEOPLE IN MORE WAYS THROUGH ENHANCED DISSEMINATION AND ENGAGEMENT AND TO BUILD A WORKFOAWORK FOR DATA-DRIVEN RESH AND HEALTH. AND I THINK THE QUESTION IS, ARE WE ACHIEVING THIS AT THE LEVEL THAT WE REALLY THINK WE SHOULD BE? AND I WOULD ARGUE, YOU CAN TELL RIGHT NOW, THAT WE'RE NOT. AND THIS IS GOING TO TAKE A SIGNIFICANT NEW REFRESH AND FRANKLY A SIGNIFICANT NEW INVESTMENT IN THIS VERY IMPORTANT AREA OF NIH. SO WHAT DOES NLM, COUPLE OF THE SIGNATURE PROGRAMS THAT IT OFFERS NOW? I'M SURE YOU'RE ALL VERY AWARE OF PROGRAMS LIKE MEDLINEPLUS, PUBMED CENTRAL, GENBANK, DBGAP, SEQUENCE READ ARCHIVE. YOU CAN SEE A LIST OF THE THREE OF HHS'S TOP FIVE WEBSITES ALL HAPPEN TO BE, THREE OF THE HOP TIEF FIVE WEBSITES ARE ALL OUT OF THE NATIONAL LIBRARY OF MEDICINE. AND THE NLM HAS EVOLVED, AS IT SHOULD, OVER MANY DECADES. STARTED IN 1836. IT WAS A COLLECTION OF BOOKS AND JOURNALS WITH ROOTS IN THE OFFICE OF THE U.S. ARMY SURGEON GENERAL AND CONGRESSIONAL AUTHORIZATION THEN MOVED NLM TO THE PUBLIC HEALTH SERVICE. IT OPENED ITS DOORS ON THE NIH CAMPUS HERE IN 1962. THEN KIND OF THE NEXT ITERATION OF NLM WAS '68 THROUGH 2000, MODERN LIBRARY EXPANSION WITH THE LISTER HILL NATIONAL CENTER FOR BIOMEDICAL COMMUNICATIONS AND THE NATIONAL CENTER FOR BIOTECHNOLOGY INFORMATION ARRIVING AT NLM, AND THEN THE NEXT YOU SEE HERE, THIS IS IN THE CURRENT VISION STATEMENT FOR NLM THE FIRST 21ST CENTURY LIBRARY WHICH NEEDS TO BE ABLE TO LEAD INNOVATIVE RESEARCH TO ACCELERATE NIH'S MISSION AND REACH SCIENTISTS AND SOCIETIES WITH TRUSTED HEALTH INFORMATION. NLM DID A STRATEGIC PLANNING PROCESS THAT WAS TO SPAN A DECADE. YOU CAN SEE HERE PREVIOUS DIRECTOR PATTI BRENNAN DESCRIBED THE NLM AS BEING POISED TO ADDRESS THE CHALLENGES LAID OUT SINCE ITS INCEPTION BY KNITTING TOGETHER THE BEST OF SEVERAL SERVICES TO EFFICIENTLY AND EFFECTIVELY ADVANCE HEALTH AND BIOMEDICAL DISCOVERY THROUGH INNOVATION. THAT WAS 2017. THINGS HAVE CHANGED A LOT SINCE 2017. I THINK THAT THREE PILLARS REMAIN VERY IMPORTANT TO INNOVATE CREATE AND MAINTAIN A SUSTAINABLE DATA ECOSYSTEM TO KEEP PACE WITH THE DATA DEMANDS OF OUR RESEARCH ENTERPRISE. THAT CLEARLY REMAINS REALLY IMPORTANT. TO ENGAGE A WIDE RANGE OF AUDIENCES TO ENSURE THE RIGHT INFORMATION GETS DELIVERED TO THEM AT THE RIGHT TIME, AND TO INSPIRE AND EMPOWER THE DATA-DRIVEN WORKFORCE OF THE FUTURE. BUT ESPECIALLY THAT MAYBE THE FIRST ONE AND THE THIRD ONE HAVE CHANGED ENORMOUSLY SINCE 2017, WHEN THIS STRATEGIC PLAN WAS FIRST -- WAS DEVELOPED. AND WE KNOW WE'VE BEEN TALKING ABOUT THE BASIC SCIENCE LABORATORY, THE CLINIC AND THE COMMUNITY AND THE IMPORTANCE OF INTEGRATING EVERYTHING THAT NIH DOES ACROSS THOSE THREE MAJOR FEATURES, THOSE THREE MAJOR RESEARCH AREAS, AND WHAT BINDS THAT ALL TOGETHER AND MAKES THAT TOGETHER MAKES IT POSSIBLE OBVIOUSLY ARE DATA, AND I WOULD ASK THE QUESTION DO WE REALLY HAVE THE DATA ECOSYSTEM NEEDED TO MAKE THIS WORK FOR US IN 2024 AND BEYOND? THERE'S ALSO A VERY BIG DISCUSSION OCCURRING ON A NATIONAL LEVEL, THE NATIONAL -- THIS IS JUST ONE EXAMPLE THAT I'M SURE YOU ALL KNOW ABOUT, THE NATIONAL AI RESEARCH RESOURCE, A SHARED RESEARCH INFRASTRUCTURE TO FACILITATE ACCESS TO COMPUTE, SOFTWARE, DATASETS, MODELS, TRAINING AND USER SUPPORT FOR RESEARCHERS AND STUDENTS. THIS IS AN ENTERPRISE ACROSS AS YOU SEE THERE ON THE BOTTOM MULTIPLE FEDERAL AGENCIES. IT'S LED BY THE NSF. THE OBJECTIVE IS TO STRENGTHEN AND DEMOCRATIZE THE U.S. AI INNOVATION ECOSYSTEM IN WAYS THAT PROTECT PRIVACY, CIVIL RIGHTS AND CIVIL LIBERTIES. SO OBVIOUSLY THE MAJOR CHANGE WE SEE IS THE ARRIVAL OF MACHINE LEARNING THAT IS REALLY -- THESE METHODS ARE NOW JUST PROLIFERATING AT AN UNPRECEDENTED PACE, AND THAT REALLY HAS CHANGED THE WAY WE THINK ABOUT DATA COMPLETELY. IT CERTAINLY DRAMATICALLY CHANGED THE WAY WE THINK ABOUT THE DEMAND FOR VERY DIVERSE AND VERY INCLUSIVE DATA ON A SCALE THAT WE'VE NEVER SEEN BEFORE. AND THAT WE KNOW WE DON'T HAVE. AND YOU CAN SEE THE GOALS LISTED HERE OF THIS NEW -- OTHERWISE KNOWN AS NAIR, NATIONAL AI RESEARCH RESOURCE, I WOULD ALSO SAY INCREASE THE DIVERSITY OF THE DATA WE ARE USING TO INFORM THESE NEW METHODS, IMPROVE U.S. CAPACITY FOR RESEARCH AND DEVELOPMENT, AND ADVANCE ARTIFICIAL INTELLIGENCE METHODS IN A TRUSTWORTHY MANNER. SO WHAT DO WE PROPOSE FROM NLM? I'LL JUST GO OVER SOME VERY SPECIFIC THOUGHTS. WHAT CAN NLM BE? A FEDERATED BIOMEDICAL RESEARCH SHARING, DATA SHARING INFRASTRUCTURE. PUBLICATION DATASETS FOR ALL NIH-FUNDED RESEARCH. A CENTRALIZED CATALOG OF DATA HOLDINGS AND USE MODELS. DRAMATIC EXPANSION OF DATA STORAGE CAPABILITIES, AND AN HHS INTEGRATED INFRASTRUCTURE TO OBTAIN DATA FROM THE CLINICAL CARE ENVIRONMENT. SO WE'RE AT AN INFLECTION POINT WHERE EVERY ENTERPRISE, EVERY LABORATORY, EVERY INSTITUTE AND CENTER ACROSS NIH HAS NEEDED ITS DATA SYSTEM, HAS BUILT ITS OWN DATA SYSTEM, HAS PAID FOR ITS OWN INFRASTRUCTURE. AND NOW WE'RE AT AN INFLECTION POINT WHERE WE'RE MOVING TO A BIG AND SHARED SPACE, AND HOW DO WE CATALYZE THAT SHIFT PROPERLY? HOW DO WE CONTINUE TO MAINTAIN THE AGENCY AND ACTIVITY OF INDIVIDUAL EFFORTS WHILE ALLOWING EVERY INDIVIDUAL EFFORT TO CONTRIBUTE TO THE BIGGER WHOLE. SO THIS IS THE INFRASTRUCTURE ISSUE THAT WE'RE STRUGGLING WITH AS WE THINK ABOUT THE NEW ITERATION OF THE NLM. WHAT ELSE DO WE NEED TO SEE? WELL, WE NEED TO SEE COLLABORATIVE DATA SHARING AND USE VIERPTS. I MEAN, WE DON'T WANT JUST TO SHARE DATA. WE WANT THE DATA TO BE USED, AND THAT'S A VERY DIFFERENT THING. DATA SHARING IS ONE THING. ACTUALLY MAKING SURE THAT THOSE DATA ARE CONFIGURED AND APPROPRIATELY PRESENTED SO THAT THEY CAN ACTUALLY BE USED AS CRITICAL. AND WE HAVE SOME GREAT EXAMPLES OF THIS ALREADY. THAT WE CAN EXPAND UPON. GENOMIC SCIENCE -- ANVIL. EVERYONE KNOWS ANVIL, AND OTHER INITIATIVES YOU SEE HERE. I'LL GIVE YOU ANOTHER GREAT EXAMPLE, THE NATIONAL COVID COHORT COLLABORATIVE, A RELATIVELY NEW ONE HERE HAS MADE SOME MAJOR CONTRIBUTIONS TO OUR UNDERSTANDING OF WHAT'S HAPPENING NATIONWIDE IN RESPONSE TO THE NEW PANDEMIC, AND YOU CAN SEE THE OTHERS LISTED HERE. THESE ARE ALREADY INCREDIBLY SUCCESSFUL SUCCESSFUL, PRODUCTIVE DATA SHARING INITIATIVES, BUT AS I SAID THEY LIVE WITHIN THEIR OWN ENVIRONMENTS, THEY'RE MAINTAINED IN MANY DEGREES BY MANY ICs. WHAT'S THE ROLE OF THEM WITH RESPECT TO A BIGGER NATIONAL LIBRARY? AND THEN, OF COURSE, WE NEED -- WHAT ABOUT EDUCATION PROGRAMS? WHAT ABOUT EDUCATION PROGRAMS THAT CAN HELP PROMOTE EQUITABLE RESOURCE AVAILABILITY AND USE? A DATA SCIENCE LEARNING CENTER, FOR EXAMPLE, UNDERSTANDING THAT DATA SCIENCE AND DATA SCIENCE WORKFORCE DEVELOPMENT IS A CRITICAL NEED OF BIOMEDICAL RESEARCH. SO THE OTHER EXAMPLE YOU HEARD ABOUT THE HEAL INITIATIVE TODAY AND I THINK THIS IS A GREAT EXAMPLE OF YET AGAIN ANOTHER WAY THAT THE THINKING HAS COMPLETELY CHANGED. I DON'T THINK WE REALIZE HOW DIFFERENT THIS IS THAN THINGS WERE JUST 10 YEARS AGO. AND SO AN INITIATIVE LIKE HEAL HAS BEEN BUILT FROM THE VERY BEGINNING TO PRODUCE ITS OWN DATA EEBCO ECOSYSTEM AND SETS AN EXAMPLE FOR OPEN SCIENCE. AND YOU CAN SEE HERE THIS LITTLE DIAGRAM FROM OUR HEAL COLLABORATORS SHOWING HOW ONE OF THE PRIMARY GOALS FROM THE BEGINNING OF THE HEAL INITIATIVE WAS A USER-FRIENDLY INFRASTRUCTURE AND CENTRALIZED DAVE DATA MANAGEMENT RESOURCES O TRANSLATE INDEPENDENT DISCONNECTED DATA INTO CONNEC CONNECTED, WELL ANNOTATED INSIGHTS. WELL, I COULD TAKE THAT SAME LITTLE SENTENCE THERE THAT YOU SEE ON THE RIGHT AND SAY, WELL, WOULDN'T IT BE GREAT IF WE HAD NLM DOING THAT AT SCALE FOR EVERYTHING THAT WE DO IN BIOMEDICAL RESEARCH? SO HERE YOU SEE A LITTLE DIAGRAM OF SOME -- THERE'S BEEN SOME DEEP THINKING ABOUT THIS, SOME WORK ALREADY, AND A PROPOSAL, SOME THOUGHTS ABOUT WHAT THE NLM OF THE FUTURE MIGHT LOOK LIKE. A PLATFORM FOR BIOMEDICAL DISCOVERY AND DATA POWERED HEALTH. WHERE ELSE IS THIS GOING TO BE? WE ARE THE LARGEST FUNDER OF BIOMEDICAL RESEARCH IN THE WORLD, AND WE HOUSE THE NATIONAL LIBRARY OF MEDICINE. I CAN'T THINK OF ANYWHERE ELSE MORE APPROPRIATE TO REALLY MOVE INTO THE FUTURE AND BE A PLATFORM FOR BIOMEDICAL DISCOVERY AND DATA POWERED HEALTH IN A MUCH BIGGER WAY THAN WE'VE BEEN BEFORE. AND I'M GOING TO GO THROUGH A FEW -- SOME OF THESE CONCEPTS THAT ARE UNDERLYING THIS NEW VISION FOR NLM INDIVIDUALLY. SO FIRST, SERVE AS AN INTERACTIVE AND PRODUCTIVE LEADER WITHIN THE INTERNATIONAL COMMUNITY OF BIOMEDICAL DATA SCIENCE ORGANIZATIONS. WORKING TO PROVIDE STABILITY AND FUNCTIONALITY OF THE BROADER BIOMEDICAL DATA ECOSYSTEM. I'M STARTING RIGHT THERE BY SAYING THAT THE NLM ALSO NEEDS TO THINK OF ITSELF AS A MEMBER, YOU KNOW, AS A CITIZEN OF THE WORLD. AND AS A RESOURCE. AND YOU CAN SEE HERE THAT WE WOULD LIKE -- ONE OF THE -- PART OF THE VISION FOR THE NLM IS TO REALLY BE AN INTERACTIVE AND PRODUCTIVE LEADER IN THE INTERNATIONAL COMMUNITY. HERE'S ANOTHER, PROVIDE A FRONT DOOR WHERE BIOMEDICAL OR CLINICAL RESEARCH DOMAIN EXPERTS, TRAINEES, PATIENT, ADVOCATES OR ANYBODY SEEKING ANSWERS TO NOVEL RESEARCH QUESTIONS CAN OBTAIN ACCESS TO REQUIRED DATA AND ANALYTIC TOOLS AS WELL AS CONSULTATION IN DATA SCIENCE. OF COURSE, WE WILL HAVE OUR CONTROLLED ACCESS DATASETS FOR VARIOUS REASONS. THERE ARE -- WHILE THE DEFAULT IS ALWAYS TO SHARE DATA, BE AS OPEN AS POSSIBLE, THERE WILL ALWAYS BE REASONS WHY TO BE RESPECTFUL TO OUR PATIENTS, TO PEOPLE WHO PARTICIPATE IN RESEARCH, WE WILL HAVE SOME CONTROLLED ACCESS. YOU KNOW, TO PROTECT CONFIDENTIALITY, ET CETERA. BUT THE THAT CAN'T INHIBIT THE ABILITY OF SCIENCE SO GO FORWARD. SO THERE'S GOT TO BE A PLACE WHERE ACCESS IS UNDERSTOOD, IT'S PROPERLY MANAGED, AND THE ATTITUDE IS, WE WANT THE DATA TO BE USED AS OFTEN AND AS MUCH AND AS THOROUGHLY AS POSSIBLE. SO THAT IS THE DEFAULT. ALWAYS PROTECT THE PEOPLE THAT WE HAVE A COMMITMENT TO HONOR, BUT ONCE THAT IS DONE, REALLY TRY TO MAKE SURE THAT THIS IS USED AS BROADLY AS POSSIBLE. AND THEN HERE'S ANOTHER ONE. WE CAN'T IMAGINE THE OLD LIBRARY, THE OLD BOOKS ON THE SHELF IS NOT GOING TO BE -- IS NOT THE LIBRARY OF THE 21ST CENTURY. AND WE DON'T ENVISION ALL THE BIOMEDICAL DAY TALL OF THE U.S N THE NLM ITSELF, MAINTAIN AN OPEN, SCALABLE, FEDERATED DIGITAL ECOSYSTEM FOR ACCESS TO BIOMEDICAL DATA AND ANALYTICS. I CAN GIVE YOU -- I'LL GIVE YOU A GOOD EXAMPLE ABOUT THIS IN THE NEXT SLIDE. THIS IS ALSO ANOTHER VERY CRITICAL NEED THAT I THINK THE M CAN PLAY AN ABSOLUTELY ESSENTIAL ROLE. WE HAVE NEEDED THIS FOR SO LONG. THAT IS TO PROVIDE A FOCUS FOR COLLECTION OF DATA FROM THE CLINICAL CARE ENVIRONMENT. IN OTHER WORDS, REAL WORLD DATA. THERE IS NOW A CROSS-AGENCY INITIATIVE WITHIN HHS THAT IS ADDRESSING AN URGENT NEED FOR HIGH QUALITY COMPREHENSIVE DATA FROM THE CLINICAL CARE ENVIRONMENT TO GENERATE EVIDENCE REQUIRED FOR DECISION-MAKING TO IMPROVE HEALTH. OUR DATA SYSTEM, OUR CLINICAL DATA SYSTEM RIGHT NOW IS VERY, VERY FRAGMENTED, BUT THERE HAS BEEN A MANDATE WITH THE 21ST CENTURY CURES ACT TO REALLY BEGIN TO USE THE ELECTRONIC HEALTH RECORD TO CREATE A LEARNING HEALTH SYSTEM, AND USE DATA WIDELY FOR HEALTH. THIS INITIATIVE ACROSS HHS ATTEMPTS TO BUILD THE INFRASTRUCTURE THAT CAN ALLOW THIS TO HAPPEN. WE THINK THAT FACILITATING LEARNING HEALTH SYSTEM INITIATIVES WILL ACHIEVE -- BY ACHIEVING BETTER ACCESS -- DATA TO ASSESS HEALTH OUTCOMES THAT MATTER TO INDIVIDUAL PEOPLE AND TO SOCIETY OVERALL IS A MAJOR COMPONENT OF BEING ABLE TO DRIVE BETTER HEALTH. WE WANT TO ELIMINATE COSTLY DATA FORMATTING AND COLLECTION REDUNDANCIES THAT CREATE SILOS. REDUCE CLINICAL CARE SITE BURDEN FOR DATA SUBMISSION, INCREASE DATA QUALITY AND SPEED TIME TO DATA ACCESS FOR USE IN AGENCY DECISION-MAKING, AND BE ABLE TO APPLY NEW MACHINE LEARNING METHODS TO HEALTH DATA THAT ARE COMPREHENSIVE AND REPRESENT THE DIVERSITY OF THE U.S. POPULATION. SO NOW I'LL GIVE YOU AN EXAMPLE AND IT ALSO SPEAKS TO THE PREVIOUS SLIDE ABOUT WHY THIS SYSTEM WILL BE FEDERATED. THE SEER REGISTRY. THE SEER REGISTRY IS REALLY IMPORTANT. THAT'S WHERE WE GET OUR REPORT CARD EVERY YEAR ABOUT HOW ARE WE DOING WITH CANCER IN THE UNITED STATES. SEER REGISTRY IS INCREDIBLY IMPORTANT AND VALUABLE, BUT IT WAS CREATED QUITE A LONG TIME AGO WITH THE OLD WAY WE USED TO THINK ABOUT DATA. WHAT HAPPENS TODAY? EVERY INSTITUTION HAS A PILE OF DATA MANAGERS, AND THEY ARE INPUTTING DATA FROM THEIR ELECTRONIC HEALTH RECORDS INTO A SEER REPORTING SYSTEM WHICH GOES TO A LOCAL PUBLIC HEALTH SYSTEM REPORTING SYSTEM AND THEN IS GATHERED IN THROUGH -- GOES THROUGH MORE LEVELS OF CURE RANGE OF MOTION AND MANAGEMENT N AND MANAGEMENT AND EVENTUALLY ENDS UP IN THE SEER DATASET. BY THE TIME WE GET THE SEER DATA, IT'S THREE YEARS OLD. BECAUSE OF ALL THAT STUFF BECAUSE OF ALL THAT STUFF THAT HAS TO HAPPEN. AND EVERY INSTITUTION IS PAYING FOR NOT ONE OR TWO OR THREE BUT THE BIG ONES, 10 OR 20 FTEs JUST TO REPORT FOR SEER. THIS DOESN'T MAKE A LOT OF SENSE IN 2024. SO BUT TOGETHER WITH THAT, THERE IS ALSO NOW DATA THAT'S BEING COLLECTED BY CMS FOR AN ENHANCED ONCOLOGY MODEL. UM DATA. IT'S HEALTH QUALITY, CARE QUALITY. IT COLLECTS, BECAUSE IT'S CANCER, SO ONCOLOGY, IT COLLECTS THE SAME DATA, MUCH OF THE SAME DATA THAT THE SEER REGISTRY IS COLLECTING. BUT WHAT DO WE DO TODAY? THEY HIRE MORE PEOPLE. NOW THESE PEOPLE ARE DOING THE ENHANCED ONCOLOGY MODEL DATA SUBMISSIONS AND IT GOING THROUGH A TOTALLY DIFFERENT SYSTEM. HERE'S WHAT WE'RE TRYING TO ACHIEVE. WE WILL HAVE ONE SYSTEM OF COLLECTING BOTH OF THESE DATA. IT WILL COME SEAMLESSLY FROM THE ELECTRONIC HEALTH RECORD RATHER THAN THROUGH ALL OF THESE REDUNDANT POLICIES, AND I WON'T SAY WE WILL COMPLETELY ELIMINATE HUMAN INVOLVEMENT IN THIS PROCESS, THAT'S ASKING FOR WAY TOO MUCH. BUT I THINK YOU CAN SEE THE IDEA HERE. AND WE HAVE SO MANY TOOLS NOW THAT CAN MAKE THIS POSSIBLE. SO WE WANT TO SEE -- AND FINALLY, WHAT IS THIS? THIS IS A FEDERATED DATA SYSTEM. WHY? WE WOULD NEVER HOLD ALL OF THE SEER DATA OR ALL OF THE DATA FOR EVERYONE IN THE UNITED STATES. SO WHAT WOULD HAPPEN IS THERE WOULD BE A CALL FOR SEER REGISTRY DATA 2024, THAT DATA WOULD COME IN AND FORM A DATASET. BUT THE DATA ITSELF WOULD LIVE WITHIN THE ELECTRONIC HEALTH RECORDS OF THE TREATING INSTITUTIONS. IF YOU THINK ABOUT THIS, IF YOU THINK ABOUT DATA NOW FROM THE CLINICAL CARE ENVIRONMENT AND EVERYTHING WE WANT TO USE IT FOR, ACCORDING TO THIS NEW MODEL, I THINK YOU CAN SEE THE BENEFIT OF WORKING TO ACHIEVE THIS. SO WHERE WOULD THIS HAPPEN? THIS WOULD YET BE ANOTHER INITIATIVE THAT WOULD FALL UNDER THE NEW NLM. ANOTHER IMPORTANT POINT, SERVE AS AN EPICENTER FOR NIH-FUNDED RESEARCH TO ADVANCE INFORMATION SCIENCE, ANALYTICS AND DATA SCIENCE. NLM CAN BE -- IS TODAY BUT CAN BE EXPANDED IN MAJOR WAYS AS BOTH EXTRAMURAL AND INTRAMURAL RESEARCH PROGRAMS TO CONDUCT INNOVATIVE RESEARCH AND TRAINING IN COMPUTATIONAL BIOLOGY AND HEALTH SCIENCES. AND YOU CAN SEE HERE SOME CRITICAL AREAS OF IMPORTANCE IN BEING ABLE -- THAT COULD BE COORDINATED THROUGH THE NLM FOR THAT. AND THEN FINALLY, PROVIDE EDUCATIONAL PROGRAMS TO EQUITABLY EXPAND THE BIOMEDICAL INFORMATICS AND DATA SCIENCE CAPABILITIES OF THE RESEARCH WORKFORCE, HEALTH IT AND HEALTH DATA STANDARDS. WELL, THAT'S REALLY CRITICAL IF THIS VISION I GAVE YOU ABOUT THE ENHANCED ONCOLOGY MODEL VERSUS SEER, THERE'S GOT TO BE A PRAYS, A FOCAL POINT WHERE WE CAN MAKE SURE WE CONTINUALLY LEARN AND UPDATE OUR DATA STANDARDS. YOU'RE NEVER GOING TO BE FINISHED WITH THAT. THAT WILL BE CRITICAL. NLM MAKES CONTRIBUTIONS TO THIS TODAY. IT CAN DO SO MUCH MORE. UNIFIED MEDICAL LANGUAGE SYSTEM TERMINOLOGY SERVICES, AND THEN MOST IMPORTANT, BIOMEDICAL INFORMATICS TRAINING PROGRAM. SO YOU CAN SEE THESE ACTIVITIES THAT CURRENTLY ECK SIT UNDER NLM CAN BE DRAMATICALLY EXPANDED. SO I'M JUST GOING TO END AND SAY YOU HEARD ME TALK ABOUT YESTERDAY WHEN DR. MON MOONEY WS HERE, WE ARE CURRENTLY RECRUITING A NEW DIRECTOR OF THE NATIONAL LIBRARY OF MEDICINE. WE REALLY LOOK FORWARD TO HAVING A NEW PERSON COME. IT CAN BE A PARTNER TO DR. SHAWN MOONEY IN BUILDING THIS NEW VISION FOR NLM FOR NLM TO BE WHAT WE REALLY NEED TO OPTIMALLY PROVIDE A NEW DATA ECOSYSTEM FOR THE 21ST CENTURY. THANK YOU, AND I'D BE HAPPY TO TAKE ANY QUESTIONS. >> I THINK THIS IS EXACTLY THE VISION THAT WE'VE BEEN HOPING FOR, FOR THE NLM, AND THAT INDIVIDUALLY WE DO IN OUR INS INSTITUTIONS AT A SMALLER SCALE. I MUST ALSO SAY THAT WITH NLM'S TRAINING PROGRAMS AND RESEARCH GRANTS, MANY THINGS THAT WELL WE DEVELOPED FOR RESEARCH USED IN OPERATIONS THESE DAYS, THAT'S HOW VALUE BASED CARE IS BASED ON HAVING ALL THAT DATA AND INFORMATION, SO VERY EXCITING TIMES. >> WELL, THANK YOU FOR THAT, AND OBVIOUSLY IF WE'RE GOING TO MOVE ON TO THIS VISION, IT REALLY HAS TO INVOLVE EVERYONE ACROSS THE BIOMEDICAL RESEARCH INFRASTRUCTURE, AND IT WILL HAVE TO BE -- BECAUSE OF THAT, IT WILL HAVE TO BE A LEARNING ENVIRONMENT ITSELF. AT NLM TO MAKE SURE THE STANDARDS, THE STRUCTURES, EVERYTHING IS DEVELOPED OR PROPERLY COORDINATED SO WE REALLY LOOK FORWARD TO WORKING WITH ALL THOSE OUT THERE WHO ALREADY ARE DOING THIS, MAYBE AT A SMALLER SCALE IN THEIR OWN INSTITUTIONS. ATUL. >> SO FIRST OF ALL, I'LL JUST SAY I WAS BLOWN AWAY BY THIS PRESENTATION. YOU HAD SOMETHING INCREDIBLY VAGUE ON THE AGENDA, LIKE DATA SHARING COMMUNITIES. I HAD NO IDEA THIS WAS COMING. SO I'VE BEEN DILIGENTLY TAKING NOTES, ABSOLUTELY BLOWN AWAY. OF COURSE THERE'S NO REASON TO ARGUE AGAINST ANYTHING YOU SAID. I MEAN, THIS HAS BEEN LONG IN COMING, I THINK EVEN THIS WORD LIBRARY HAS WEIRD CONNOTATIONS TO PEOPLE, SO I REALLY CAN'T ADD TO ANYTHING YOU SHOWED. IF I HAD TO ADD ONE THING, THOUGH, AND I THINK YOU MIGHT RESONATE WITH THIS AS WELL, LET'S KEEP THE PUBLIC FACING SIDE OF A LIBRARY PUBLIC FACING, AND THAT ALSO MEANS PATIENTS AND THE WORLD AND THE COMMUNITIES, SO NOT JUST THE RESEARCHERS, YOU KNOW AS WELL AS I DO, A PATIENT TODAY WITH A RARE DISEASE OR SOME CONDITION THAT NEEDS A COMPLEX NEXT SET OF THINKING TURNS TO GOOGLE TODAY, AND THEY'LL FIND HEALTH SYSTEMS THAT ARE PAID-FOR ALZHEIMER'S DISEASES THAT GET THAT RARE DISEASE PATIENT TO THEIR CENTER. THERE'S NO REASON IN THE WORLD WE COULDN'T BUILD PORTALS THAT ARE PATIENT FACING OUT OF THE NLM THAT USE THIS FEDERATED DATA RESOURCE OF THE FUTURE, AND A PATIENT WITHOUT A LOT OF PRIVILEGE CAN SEARCH AND FIND WHICH HEALTH SYSTEMS ARE THE BEST AT TAKING CARE OF THAT DISORDER AND HOPEFULLY GET SOME CARE NEARBY OR FAR BUT LET'S CONTINUE TO REALLY EMPOWER PATIENTS IN THE COMMUNITY, I KNOW YOU HAVE THAT IN MIND. I'M NOT SAYING THIS AT ALL CRITICALLY, BUT I'M JUST AGAIN BLOWN AWAY BY THIS PRESENTATION, ABSOLUTELY SURPRISING. >> THANK YOU. ALSO WHEN WE WERE FIRST TOSSING AROUND THIS IDEA, I SAID WOW, WOULDN'T IT BE AMAZING IF A HIGH SCHOOL STUDENT IN WIE HOMING, WYOMING, AHIGH SCHOOL STUDENT CE SOME BRILLIANT IDEA FOR THEIR SCIENCE PROJECT AND BE ABLE TO GO INTO THE NLM AND ACTUALLY GET THE DATA THEY NEED TO DELIVER AN AMAZING INSIGHT. WHY NOT? AND ALSO BE ABLE TO GO TO THE NLM AND FIND LINKS AND ACCESS TO THE TOOLS THAT WILL HELP THEM DO IT. I MEAN, YOU COULD REALLY THINK ABOUT CROWDSOURCING, CROWDSOURCING RESEARCH IN A WAY WE NEVER HAVE BEEN ABLE TO DO BEFORE. WELL, THIS IS GOING TO TAKE A LOT. I DO NOT UNDERAPPRECIATE THE FACT THAT WE'VE STILL GOT SOME OBSTACLES TO OVERCOME. WE'VE GOT SOME FORMATTING, WE'VE GOT -- BUT I AM SO -- GIVEN WHAT'S HAPPENED JUST EVEN IN THE LAST YEAR, I'M SO OPTIMISTIC THAT WE'RE READY FOR THIS, AND IT'S TIME FOR US TO STEP UP. NIH IS NOT IN THE MOST GENEROUS FUNDING ENVIRONMENT THAT IT'S BEEN IN FOR A WHILE, BUT WE CAN'T WAIT. WE CAN'T WAIT FOR A BIG INFUSION OF CASH INTO NLM, SO LIKE WE'RE DOING WITH THESE OTHER URGENT THINGS, WE'RE COORDINATING, REPURPOSING. WE HAVE BEEN -- THE PRESIDENT'S BUDGET IN THIS NEXT COMING YEAR IS PROVIDING A $30 MILLION UPGRADE TO NLM AND THAT WILL HELP US GET STARTED. AND THEN CERTAINLY WITH COLLABORATION ACROSS ALL OF OUR INSTITUTES AND CENTERS, WE'RE GOING TO GO FULL IN ON THIS. >> DR. SOLOMON PUT A COMMENT IN THE CHAT. PERHAPS YOU CAN REPEAT IT, DR. SOLOMON, BECAUSE DR. BERTAGNOLLI IS NOT ABLE TO SEE THE CHAT BOX RIGHT NOW. >> THANKS. >> SURE. I JUST WANTED TO SAY THAT I AGREE WITH EVERYTHING ATUL SAID, AND IN CONSIDERATION OF THE GENERAL PUBLIC, KEEP IN MIND THE LIMITATIONS OF THE DIGITAL WORLD AND OUR ROLE IN REMOTE COMMUNITIES, AND WITH THAT, THE SKILLS IT TAKES TO SEARCH AND USE THE LIBRARY. I MISS THE BOOKMOBILE. I KEEP TRYING TO PUT THIS IDEA FOR THE BOOK MOBILE 2.0 THAT WOULD DRIVE INTO YOUR NEIGHBORHOOD AND YOU COULD CHECK OUT BOOKS, AND IF YOU CAN THINK OF THAT, THAT SAME GIFT THAT IT GAVE TO CHILDREN ALL OVER THE UNITED STATES, BUT IN A 2.0 VERSION OR MAYBE WE'RE AT 5.0 VERSION, I'M NOT SURE, BUT JUST REALLY ACCELERATING, AND WITH THAT, YOU KNOW, I WAS AMAZED ONE TIME ON THE RESERVATION WORKING WITH SOME ELDERS WHO DIDN'T SPEAK. SO ENGLISH WAS NOT THEIR FIRST LANGUAGE. THEY SPOKE THEIR TRADITIONAL LANGUAGE AND THEY WORE THEIR TRADITIONAL GOWNS AND GARBS, AND WE WERE TALKING ABOUT TRADITIONAL HEALING, SO I COULDN'T UNDERSTAND ANYTHING. BUT IN THE MIDDLE OF THE CONVERSATIONS, RICKEY MARTIN SONG COMES ON THEIR CELL PHONES AND THEY KNOW HOW TO USE THEIR CELL PHONES. THAT'S A SOURCE THAT THEY KNOW HOW TO USE. SO IT'S ABOUT TAKING THE TECHNOLOGY THAT'S SO ADVANCED AND MAKING IT REALLY USABLE FOR THOSE COMMUNITIES WHO DON'T REALLY HAVE THAT KIND OF ACCESS LIKE I DO SITTING HERE AT MY HOUSE. LISTENING TO ALL THIS WONDERFUL STUFF YOU GUYS ARE DOING. SO THAT'S JUST MY COMMENT. THANK YOU. >> THANK YOU. I THINK THIS IS WHY PEOPLE KEEP SAYING, WELL, DON'T CALL IT THE NATIONAL LIBRARY OF MEDICINE ANYMORE. CALL IT THE NATIONAL -- I DON'T KNOW -- BIOTECHNOLOGY DATA CENTER. AND I'VE BEEN PUSHING BACK ON THAT BECAUSE REMEMBER THE LIBRARIAN WHEN YOU WERE A KID AND NEEDED TO DO YOUR REPORT, YOU ASK THE LIBRARIAN WHERE YOU FOUND WHAT YOU NEEDED. SO I THINK THE CONCEPT OF THE NATIONAL LIBRARY OF MEDICINE NOT ONLY BEING THE REPOSITORY WHERE ALL THIS STUFF SITS, BUT BEING THE ASSISTANT TO HELP RESEARCHERS GET THE ACCESS THEY NEED AND UNDERSTAND WHAT'S THERE IS ALSO A CRITICAL PART OF THIS. AND I THINK YOU JUST ILLUSTRATED THAT, SO THANK YOU. WELL, I'LL JUST SAY IT AGAIN, WE'RE LOOKING FOR A NEW DIRECTOR, SO WHO CAN WE GET OUT THERE? I'LL PUT A CALL OUT TO THE WHOLE COMMUNITY. WE NEED A REALLY, REALLY BRILLIANT FORWARD-THINKING PERSON WHO CAN BE DR. MOONEY'S PARTNER TO BRING THIS TO REALITY. SO PUTTING OUT A CALL FOR ANYONE WHO'S INTERESTED TO LET US KNOW. THANK YOU SO MUCH. ARE WE GOOD? ANYBODY ELSE? >> WE'RE GOOD, AND I THINK WE COULD PROBABLY GO TO THE NEXT TOPIC BECAUSE IT'S TO FORM A WORKING GROUP PROPOSAL. SO WE'RE A LITTLE AHEAD BUT I THINK WE'RE OKAY HERE. TO TALK ABOUT CREATION OF AN AI WORKING GROUP. >> SO THANKS, MO MONICA. JUST TO TAKE TWO SECONDS TO FRAME THIS FOR SUSAN'S PRESENTATION, SOME OF YOU MAY RECALL THAT WE'VE HAD A PRIOR ACD WORKING GROUP ON ARTIFICIAL INTELLIGENCE AND MACHINE LEARNING, AND SUSAN WILL ACTUALLY REVIEW A LITTLE BIT OF THAT AND IT WAS A VERY PRODUCTIVE WORKING GROUP, BUT TO SAY THE OBVIOUS, THIS FIELD IS MOVING SO FAST THAT WE FELT THAT A REFRESH WOULD BE IN ORDER, PARTICULARLY GIVEN THE NEXUS OF WHAT'S GOING ON IN CIT THAT YOU'VE HEARD YESTERDAY, WHAT WILL BE GOING ON IN NLM AS YOU JUST HEARD FROM THE NIH DIRECTOR, SO THE TIMING, WE THINK, SEEMS RIGHT, BUT AS WE DO WITH WORKING GROUPS, WE PRESENT TO THE COUNCIL FOR THEIR CONSIDERATION. SO WITH THAT, I WILL TURN IT OVER TO SUSAN TO DO THE PRESENTATION, THEN I'LL COME BACK AT THE VERY END WITH THE PROPOSED CHARGE. SO SUSAN, PLEASE. >> THANK YOU SO MUCH, DR. TABAK. JUST CHECK, YOU CAN HEAR AND SEE ME OKAY, CORRECT? >> YES. YOU'RE COMING IN WELL. >> I APOLOGIZE THAT I CANNOT BE THERE IN PERSON TODAY. BUT I AM JUST THRILLED TO BE HERE VIRTUALLY, AND I'M ALSO REALLY THRILLED TO WORK ACROSS NIH ON THE WORK THAT WE'RE DOING IN ARTIFICIAL INTELLIGENCE AND WHAT YOU'RE GOING TO SEE IN JUST THIS FEW 30 MINUTES IS AN IMPRESSIVE ARRAY OF ACTIVITIES THAT WE HAVE DONE SINCE 2019, SO WE REALLY TOOK THOSE RECOMMENDATIONS TO HEART. YOU'LL SEE THEM IN A MOMENT. AND THANK YOU SO MUCH FOR THE OPPORTUNITY. SO FOR THE NEXT SLIDE, IT'S JUST TO FRAME HOW IMPORTANT THIS ACTIVITY OF TRUSTWORTHY AI IS ACROSS OUR ADMINISTRATION, AND WITHIN HHS AND WITHIN NIH. THERE'S A CLICK I THINK YOU NEED TO DO ONE MORE CLICK TO BRING UP THE EXECUTIVE ORDER ON SAFE AND TRUSTWORTHY AI. WHAT I CAN TELL YOU IS THAT THIS IS THE LONGEST EXECUTIVE ORDER TO DATE. I CAN'T CERTAINLY ENUMERATE EVERYTHING THAT'S IN THE EXECUTIVE ORDER. I JUST WANT TO HIGHLIGHT A FEW ACTIVITIES THAT IMPACT HHS AND CERTAINLY NIH INVESTING IN ARTIFICIAL INTELLIGENCE RELATED EEDUCATION, TRAINING, DEVELOPMENT, RESEARCH AND CAPACITY BUILDING. TO IDENTIFY AND ATTRACT TOP TALENT AND OTHER CRITICAL EMERGING TECHNOLOGIES, DR. BERTAGNOLLI TALKED ABOUT THIS, I'LL GIVE YOU A LITTLE BIT MORE INFORMATION ON THE NAIRR, TO SUPPORT THE 2024 LEADING EDGE ACCELERATION PROJECT, A PROJECT THAT'S SUPPORTED BY THE OFFICE OF THE NATIONAL COORDINATOR THAT ADDRESSES AND DOCUMENTS FAST AND EMERGING TECHNOLOGIES THAT WILL REALLY PROMOTE THE DEVELOPMENT USE AND ADVANCEMENT IN INTEROPERABLE HEALTH HERE CERTAINLY AT NIH AS WELL, AND FINALLY TO ACCELERATE THE NATIONAL INS TEULTS OF HEALTH ARTIFICIAL INTELLIGENCE MACHINE LEARNING CONSORTIUM TO ADVANCE HEALTH EQUITY AND RESEARCH DIVERSITY. I WILL TELL YOU A LITTLE ABOUT THAT AS WELL, BUT LET ME GO TO THE NEXT SLIDE. I REALLY WANT TO THANK DR. TABAK AND DR. GLAI GLAZER WHO WERE CR OF THE WORKING GROUP. THE REPORT CAME OUT IN 2019. FLAGSHIP DATA GENERATION EFFORTS, YOU'LL HEAR ABOUT THAT WITH THE BRIDGE2AI, CRITERIA FOR MACHINE LEARNING FRIENDLY DATASETS, DATA SHEETS AND MODEL CARDS, AND CONSENT AND DATA ACCESS STANDARDS, IN A RELATED EFFORT WE'VE DONE AMAZING WORK THERE. TO REALLY DEVELOP THOSE ETHICAL PRINCIPLES THAT HOLD ACCOUNTABLE INFORMED REPRESENTATION OF OUR POPULATION REALLY AT THE FOREFRONT OF THE DEVELOPMENT OF AI AND BIOETHICS. FINALLY TO ATTRACT, TO TRAIN AND TO RETAIN TALENTED WORKFORCE BY DEVELOPING CURRICULA, BY FOCUSING ENTREE KNEES AND FELLOWS AND BY CONVENIENT CROSS DISCIPLINARY COLLABORATORS. SO THAT WAS THE RECOMMENDATIONS AND HERE'S WHAT WE'VE DONE WITH THOSE RECOMMENDATIONS ACROSS NIH SINCE 2019. SO THE NEXT SLIDE IS OUR BRIDGE2AI PROGRAM, OUR FLAGSHIP PROGRAM THAT GENERATES FLAGSHIP DATASETS FOR GRAND CHALLENGES. WE ARE WORKING ON PREPARING AI AND ML-FRIENDLY DATA ACROSS NIH BUT CERTAINLY WITHIN THE BRIDGE2AI PROGRAM EMPHASIZING ETHICAL BEST PRACTICES AND PROMOTING A DIVERSE TEAM. LET ME JUST TELL YOU ABOUT THOSE GRAND CHALLENGES REALLY QUICKLY, BECAUSE THEY'RE SUPER IMPORTANT. THE FIRST ONE IS CLINICAL CARE INFORMATICS. IT'S REALLY ABOUT USING IMAGING AND CLINICAL AND OTHER DATA THAT ARE COLLECTED IN INTENSIVE CARE UNITS AND SETTING THE STAGE FOR DIAGNOSIS, AND ALSO FOR RISK PREDICTION. THERE'S THE RETURN TO HEALTH OR THE PROGRAM REALLY THINKING ABOUT HOW DO WE UNCOVER THE DETAILS OF HOW HUMAN HEALTH IS RESTORED AFTER DISEASE, SO THIS PROJECT FOCUSES ON USING FOR EXAMPLE TYPE 2 DIABETES AS A MODEL FOR UNDERSTANDING HEALTH FROM DISEASE. THE FUNCTIONAL GENOMICS PROJECT, IT'S MAPPING THE SPATIAL AND TEMPORAL ARCHITECTURE OF THE HUMAN CELLS TO INTERPRET CELL STRUCTURED FUNCTION IN HEALTH AND DISEASE. THIS IS REALLY CREATING A CELLULAR MAP OF PROTEIN-PROTEIN INTERACTIONS, PROTEIN SUBCELLULAR DISTRIBUTIONS AND TRANSCRIPTION STATES, THAT'S FAIRLY NEWLY COMPREHENSIVE ACROSS ALL OF THE CHROMATIN REGULATORS ENCODING BY THE HUMAN GENOME. AND FINALLY, A PRECISION PUBLIC HEALTH PROJECT, THIS IS THE VOICE PROJECT THAT USES VOICE AS A BIOMARKER FOR HUMAN HEALTH, REVEALING HOW GENETIC AND GENOMIC VARIATIONS AND HUMAN DEVELOPMENT BEHAVIOR AND ENVIRONMENT ARE ALL FACTORS THAT AFFECT INDIVIDUALS AND POPULATIONS IN OUR HEALTH. SO THOSE ARE THE FOUR GRAND CHALLENGES AND THE NEXT SLIDE TELLS YOU WHERE WE ARE WITH THE BRIDGE2AI. SO YOU'LL SEE THEY'RE IN THE THREE MAIN AREAS, DATA, WE'VE MADE GREAT PROGRESS. YOU CAN SEE THERE'S A PUBLIC PORTAL UP THERE IN THE FRONT OF THE SLIDE, BRIDGE2AI.ORG. WE NOW HAVE EXTERNAL RESEARCHERS THAT ARE WORKING WITH THE DATA SINCE THE PAST TWO MONTHS. THERE ARE FIVE INTERNSHIP PROGRAMS THAT TRAIN RESEARCHERS IN BOTH AI AND BIOMEDICINE. I'LL TALK A LITTLE ABOUT PARTNERSHIPS WITH BRIDGE2AI. FINALLY, THERE'S A PAPER THAT'S BEEN SUBMITTED, IT'S UNDER REVIEW THAT DISCUSSES THE ETHICAL CONSIDERATIONS AS PART OF AI AND THE AI LIFECYCLE, WHICH I CAN'T WAIT TO SEE THAT PAPER COME OUT BECAUSE IT CERTAINLY WILL BE IMPACTFUL ACROSS NIH. THE NEXT SLIDE IS HOW DO WE BUILD A VERY LARGE RESEARCH CONSORTIUM AND COHORT THAT CANNOT ONLY USE AI BUT ALSO CONTRIBUTE TO IT SO THIS IS THE AIM AHEAD PROGRAM. IT'S REALLY ABOUT THE PARTICIPATION AND REPRESENTATION OF RESEARCHERS IN COMMUNITIES THAT ARE CURRENTLY UNDERREPRESENTED IN THE DEVELOPMENT AND USE OF AI AND FOCUSING ON HEALTH DISPARITIES RESEARCH AND INEQUITIES USING AI AND FINALLY IMPROVING THE CAPABILITIES OF THESE EMERGING TECHNOLOGIES IN THESE COMMUNITIES. JUST WANT TO GIVE A SHORT OUT TO DR. LAURA BIVEN, SHE WORKED TO HELP SET UP THIS PROGRAM IN 2019 AND IT'S JUST BEEN A PLEASURE WORKING WITH HER AND WORKING WITH THE TEAM ON THIS PROGRAM. THIS IS KIND OF A BUSY SLIDE TELL YOU WHERE WE'VE BEEN IN TWO YEARS. IN JUST TWO YEARS WE'VE DEVELOPED A VERY LARGE CONSORTIUM ACROSS THE UNITED STATES THAT INCLUDED OVER 274 AWARDS TO RESEARCHERS TO REALLY ADDRESS AI AND DATA, DEVELOP THOSE ALGORITHMS AND WORK TO BUILD COMMUNITIES, AND COMMUNITY ENGAGEMENT IS A VERY CRITICAL COMPONENT OF THE AIMENM AHEAD PROGRAM. THERE'S A NUMBER OF FELLOWSHIPS BOTH LEADERSHIP FELLOWSHIPS AND RESEARCH FELLOWSHIPS, AS WELL AS PILOT PROJECTS. I'M A REAL BIG FAN OF DEVELOP PILOTS AND TRY DIFFERENT THINGS OUT FROM THAT NEW INITIATIVES AND NEW CAPABILITIES CAN EMERGE. I ALSO WANT TO TALK A LITTLE BIT ABOUT PARTNERSHIP SO THE AIM AHEAD PROGRAM IS A PARTNERSHIP PROGRAM, WE PARTNER WITH THE ALL-OF-US PROGRAM, WE HAVE OVER 25 TRAINEES THAT ARE WORKING WITHIN THE ALL-OF-US PLATFORM. AND WE ALSO PARTNER WITH THE N3C SPONSORED BY NCATS, THE NATIONAL CORE COLLABORATIVE. IT'S REALLY IMPORTANT TO PROVIDE TRAINEES AND RESEARCHERS WITH DIFFERENT TYPES OF DATA AND PLATFORMS SO THEY CAN INVESTIGATE WHAT IS REALLY GOING TO WORK WELL TO ANSWER THEIR RESEARCH QUESTIONS. FINALLY, THERE'S AN IMPRESSIVE AIM AHEAD CONNECTS PROGRAM THAT DEVELOPS MENTORS AND MENTEES ACROSS 1,306 INSTITUTIONS AND THANK YOU FOR ALL OF OUR MENTORS WHO REALLY PARTICIPATE WITH US IN THE AIM AHEAD PROGRAM. JUST WANT TO VERY QUICKLY IN THE NEXT SLIDE GIVE YOU AN INDICATION OF SOME OF THE TYPES OF RESEARCH THAT IS IN PARTNERSHIP WITH THE AIM AHEAD PROGRAM AND THE FIRST IS THE AIM AHEAD ETHICS AND EQUITABLE PRINCIPLES, THIS CAME OUT EARLIER I THINK LAST YEAR THAT PRODUCES PRINCIPLES THAT COMPROMISE FIVE CORE AREAS TO THINK ABOUT WHEN LOOKING AT DEVELOPING AN ETHICAL AI FRAMEWORK. WE ARE ALSO WORKING -- AND THIS IS SUCH A FUN PROJECT IN THE NEXT LITTLE VIGNETTE IS A PARTNERSHIP WITH THE ALEXANDRIA PUBLIC SCHOOL SYSTEM AND GEORGE WASHINGTON UNIVERSITY TO REALLY RAISE AWARENESS OF AI IN MEDICINE AMONGST SCHOOL KIDS. SO THIS IS TRULY A HANDS-ON TRAINING ACTIVITY. THESE KIDS ARE FROM UNDERREPRESENTED BACKGROUNDS AND THEY REALLY LEARN ABOUT AI, THEY ACTUALLY HELP HELP DEVELOP AI AD THEY TEST IT OUT. THERE'S A NICE PAPER THAT DESCRIBES THAT IN THE JOURNAL OF CYOF -- OF SI STE MIX AND CYBERNETICS. THIS IS LOOKING AT THE SIMPLE CLINICAL RISK MODEL FOR THROMBOSIS EMBOLISM IN CANCER PATIENTS TO IMPROVE THE ACCURACY IN USING DATA IN THE HARRIS HEALTH SYSTEM. SO JUST A SMALL VIGNETTE OF SOME OF THE WORK THAT WE'RE DOING IN AIM AHEAD THAT IMPACTS TRAINING AND RESEARCH. AND ETHICAL AI. THERE ARE A NUMBER OF NIH-WIDE COLLABORATIVE PROGRAMS ACROSS ALL OF OUR INSTITUTES, CENTERS AND OFFICES THAT DEVELOP ETHICAL BIAS AND TRANSPARENCY LOOKING AT THE ETHICAL AND TECHNICAL SOLUTIONS OF EMBEDDING ETHICS IN THE AI LIFECYCLE DEVELOPMENT OF APPLICATIONS. THIS IS SUPER IMPORTANT. YOU'LL HEAR THIS AGAIN AND AGAIN THAT WE NEED TO DEVELOP A NEW WAY OF THINKING ABOUT AI IN SCIENCE THAT IS EMBEDDING ETHICS IN THE DEVELOPMENT AND USE OF AI. THERE'S ALSO WORK WE'VE DONE WITH AND ACROSS THE ICs TO IMPROVE THE AI READINESS OF EXISTING DATA, AND YOU'LL SEE QUICKLY HOW THAT IS GOING FORWARD AND FINALLY ADDRESSING WORKFORCE GAPS IN DATA GOVERNANCE AND AI FOR BIOMEDICINE. YOU CAN SEE THE NUMBER OF INSTITUTES, INVESTIGATORS AND WORKSHOPS THAT HAVE BEEN SUPPORTED THE LAST TWO YEARS THROUGH PROGRAMS TO COLLABORATE ACROSS THE AGENCY. THE NEXT SLIDE IS REALLY A VIGNETTE OF SOME OF THE HIGHLIGHTS OF THE IMPACT OF THE WORK THAT WE'VE DONE, FOR EXAMPLE, ALEX FENERMAN'S WORK TO EXAMINE -- THE SECOND ONE IS DRO IMPUTE MISSING BRAIN IMAGES, AN ACTIVE AREA OF RESEARCH, AND ORTIZ'S WORK, HOW YOU DEVELOP FAIR AND READY AI DATA WITH APPLICATIONS TO IMPROVE DIAGNOSIS OF CANCER IN HISPANIC POPULATIONS. SO JUST A FEW VIGNETTES OF SOME OF THE WORK THAT WE'VE DONE ACROSS THE AGENCY TO SUPPORT AI READY DATA, ETHICAL AI, AND TRAINING. THE NEXT SLIDE IS REALLY THE SORT OF NEW FRONTIER. MOST OF US ARE FAIRLY FAMILIAR WITH WHAT WE CALL UNIMODAL AI MODELS FAI FAIRLY TYPICAL, BUT WHAT'S REALLY EMERGING AS A NEW FRONTIER IN AI IS MULTIMODAL AI, MULTIMODAL AI IS MORE THAN JUST COMBINING DIFFERENT INDEPENDENT TRAINING MODELS, IT'S REALLY INTEGRATING DIFFERENT MODALITIES INTO THE TRAINING AND LEARNING PROCESS IN ORDER TO MAKE A BETTER PREDICTION. THIS IS A PILOT THAT WE'RE DOING FOR TWO YEARS ACROSS THE AGENCY TO DEVELOP NEW SYSTEMS TO LEVERAGE BIOMEDICAL RESEARCH USING MULTIMODAL AI TECHNOLOGIES. IT IS A NEW FIELD OF STUDY. IF YOU GO TO ANY AI CONFERENCE, MANY TALKS ABOUT MULTIMODAL AI. WE ALSO WANT TO EU LEWIS DATE -E OPPORTUNITIES AND CHALLENGES IN USING MULTIMODAL AI IN BIOMEDICINE, A FIELD THAT IS A LITTLE UNDERREPRESENTED IN THOSE CONFERENCES, AND FINALLY, WHAT ARE SOME OF THE CONSIDERATIONS THAT WE WOULD NEED TO THINK ABOUT WHEN WE'RE DEVELOPING MULTIMODAL AI FOR BIOMEDICINE, WHAT ARE THE ETHICAL AND TRANSPARENCY CONSIDERATIONS. THE NEXT SLIDE, THERE IS A PLETHORA OF AI RESEARCH SUPPORTED BY THE NIH INSTITUTES, SO I JUST WANTED TO HIGHLIGHT ONE EXAMPLE FROM NIDA BECAUSE WE WERE TALKING ABOUT IT EARLIER IN TERMS OF WHAT ARE WE DOING RIGHT NOW TO SUPPORT ARTIFICIAL INTELLIGENCE DEVELOPMENT. FOR EXAMPLE, IN HUMAN NEUROSCIENCE. ONE OF THE THINGS THAT WE'RE LOOKING AT IS BRAIN ACTIVITY CAN BE COLLECTED USING DIFFERENT TYPES OF AI MODELS AND THEN THEY CAN BE USED TO PREDICT HEALTH OUTCOMES TO DO THAT. THESE MARKERS HAVE TO BE RELIABLE, AND WHAT RESEARCHERS ARE DOING RIGHT NOW IS THAT THEY'RE DEVELOPING AI ALGORITHMS ON VERY LARGE DATASETS AND THEN THESE CAN BE TRAINED ON LARGE DATASETS AND THEN APPLIED TO SMALLER ONES. SO THIS IS JUST A PARTICULAR EXAMPLE FROM THE WORK OF YANG WU AND OTHERS. WE COLLABORATE WITH A NUMBER OF AGENCIES, FOR EXAMPLE, WE WORK ACROSS HHS ON THE HHS AI TASK FORCE TO DEVELOP THE STRATEGIC PLAN AS WELL AS ACTIVITIES TO ADDRESS THE EXECUTIVE ORDER ON ARTIFICIAL INTELLIGENCE. WE COLLABORATE WITH DOE TO ADVANCE CANCER USING ARTIFICIAL INTELLIGENCE. SO I JUST WANT TO HIGHLIGHT A FEW OF THE WORK THAT WE DO ACROSS AGENCIES. THE NATIONAL AI RESEARCH RESOURCE OR THE NAIRR, IT'S A COLLABORATION WITH A NUMBER OF AGENCIES. NSF IS THE LEAD. YOU'LL SEE OUR WORK PERMANENTLY HIGHLIGHTED IN THE NAIRR SECURE WORK. SO THE NEXT SLIDE IS WHAT ARE WE BRINGING TO THE TABLE FOR NAIRR? FIRST OF ALL, WE HAVE THE LARGEST AMOUNT OF HIGHLY CURATED AND IN MANY CASES INTEROPERABLE AI-READY DATA THROUGH MANY OF THE PROGRAMS THAT I'VE JUST DISCUSSED AND A COUPLE OTHERS THAT I'LL BRING UP. WE KNOW HOW TO PROTECT PATIENT PRIVACY AND USE PATIENT DATA RELIABLY AND SECURELY AT NIH. THERE IS NO OTHER AGENCY I THINK THAT CAN REALLY HANDLE PATIENT DATA IN THE WAY THAT NIH CAN. NOT ONLY THAT, WE DEVELOP AND WE ARE THE LEADERS OF TRUSTWORTHY AND ETHICAL AI, NOT ONLY ADOPTING ETHICAL PRACTICES BUT REALLY THINKING DEEPLY ABOUT HOW DO YOU EMBED ETHICAL AI INTO THE DEVELOPMENT AND APPLICATION OF AI TO THE COMMUNITY. AND WE ARE A LARGE COMPONENT OF THE TRAINING CAPABILITIES OF RESEARCHERS AND STUDENTS IN ARTIFICIAL INTELLIGENCE IN BIOMEDICINE AND UTILIZING SOME OF THE ACTIVITIES I'VE JUST MENTIONED TO REALLY INCREASE AND BROADEN THAT PARTICIPATION OF AI IS REALLY WHERE NIH LEADS. SO THE NEXT SLIDE IS JUST A FEW OF THE ACTIVITIES, AND I'LL GO THROUGH EACH AND EVERY ONE OF THESE IN TERMS OF WHAT WE'RE DOING WITH THE OPEN DATASETS AND THE OPEN COMPUTATIONAL CAPABILITIES OF THE NATIONAL AI RESEARCH RESOURCE. I'LL TALK A LITTLE BIT ABOUT NAIRR SECURE. THIS IS A PARTNERSHIP WITH THE DEPARTMENT OF ENERGY TO REALLY THINK ABOUT HOW DO YOU USE AI IN A SECURE ENVIRONMENT. THERE'S OTHER WORK THAT WE'RE DOING IN DEVELOPING AI SOFTWARE IN CLASSROOMS. I WANT TO HIGHLIGHT CLOUDLAB IS A PLATFORM THAT CAN LEVERAGE TOOLS AND CAPABILITIES TO TRAIN STUDENTS AND RESEARCHERS IN AI AND FINALLY WE HAVE THE ABILITY TO OUTREACH IN AI THROUGH AIM AHEAD, THROUGH BRIDGE2AI, THE NATIONAL AI -- THROUGH THE NATIONAL COVID COHORT COLLABORATIVE AND OTHER ACTIVITIES. SPEAKING OF THAT, THE NEXT SLIDE, THANK YOU TO NCATS FOR THEIR PARTICIPATION IN THE NAIRR. THE NATIONAL COHORT COLLABORATIVE, YOU CAN SEE SOME OF THOSE STATISTICS ON THE SIDE, IS REALLY BRINGING THAT DIVERSE REPRESENTATIVE AND HARMONIZED DATASET THAT IS FOUNDATIONAL FOR BUILDING TRUSTWORTHY AND ROBUST AI. WE NOW HAVE A NUMBER OF RESEARCHERS UTILIZING THE N3C AS WE CALL TO DEVELOP AI ALGORITHMS, FOR EXAMPLE IN PREDICTING PHENOTYPES IN LONG COVID FOR RECOVERY, ONE EXAMPLE THAT REALLY HIGHLIGHTS THE DEPTH AND BREADTH OF WHAT YOU CAN DO WHEN YOU COLLECT CLINICAL RELATED DATA AND WORK WITH IT WITH ARTIFICIAL INTELLIGENCE, BUT WE'VE JUST TOUCHED THE SURFACE OF THAT CAPABILITY, AS DR. BERTAGNOLLI HAS SAID. THE NEXT SLIDE IS CREATING AI MEDICAL IMAGES. THIS IS THE WORK OF NIBIB, AND THANK YOU SO MUCH FOR PARTICIPATING IN THE NAIRR. MEDICAL IMAGES HAVE REALLY QUITE A GREAT CAPABILITY, AND THIS IS THE SWEET SPOT FOR ARTIFICIAL INTELLIGENCE LINKING THOSE MEDICAL IMAGES WITH CLINICAL DATA, AND THIS ACTUALLY HAPPENS WITHIN THE NC3 AND WITHIN THE NAIRR SO THAT RESEARCHERS HAVE NOT ONLY THE ABILITY TO INVESTIGATE ARTIFICIAL INTELLIGENCE USING THE MIDRC OR THE MEDICAL IMAGING AND DATA RESOURCE CENTER, BUT ALSO LINKING THOSE WITH CLINICAL DATA, WITH PHARMACY DATA, AND WITH OTHER DATA SUCH AS CMS DATA, THAT PROVIDES SUCH A RICH APPLICATION OF DATA FOR ARTIFICIAL INTELLIGENCE, AND YOU CAN CERTAINLY UNDERSTAND WHY WE WOULD LIKE TO HAVE THE CAPABILITY WITHIN A SECURE ENVIRONMENT, AND HENCE THIS IS WHY WE ARE LEADING THE NAIRR SECURE FOR BIOMEDICINE. THE NEXT SLIDE IS STARTING TO DISCUSS A LITTLE BIT ON WHAT WE'RE DOING WITH THE OPEN DATASETS. THERE ARE REALLY WONDERFUL OPEN DATASETS THAT CAN BE MADE AVAILABLE TO RESEARCHERS THROUGH THE NAIRR. I JUST WANT TO CALL OUT IMMPORT, A LONG-STANDING DATA RESOURCE THAT PROVIDES AND SUPPORTS ARTIFICIAL INTELLIGENCE IN IMMUNOLOGY, THERE'S SOME WONDERFUL STATISTICS, AND I WANT TO THANK NIAID AND THE RESEARCHERS WHO PARTICIPATE IN THE NAIRR THROUGH IMMPORT. AND THE NEXT SLIDE IS THE WORK THAT WE'RE DOING WITH NIMHD, AND THANK YOU SO MUCH FOR PARTICIPATING IN THE NAIRR. IT'S THE SCHARE PLATFORM. THIS PLATFORM SCHARE IS A CLOUD-BASED PLATFORM. IT HOSTS OVER 245 NATIONALLY FEDERATED DATASETS THAT FOCUS ON POPULATION SCIENCE, SOCIAL DETERMINANTS OF HEALTH AND ENVIRONMENTAL AND BEHAVIORAL DATA. IN PARTICULAR, WE'RE BRINGING THE HEALTH EQUITY ACTION NETWORK TO THE NAIRR. IT FOCUSES ON CHRONIC DISEASE. IT'S A NUMBER OF INVESTIGATOR INITIATED PROJECTS THAT WILL BRING DATA FOR THE NAIRR AND IT ALIGNS WITH OUR GOALS AT NIH TO CREATE COMMON DATA ELEMENTS THAT CAN BE SHARED ACROSS RESOURCES, FOR EXAMPLE, IN THIS PARTICULAR CASE, WE'RE LOOKING AT SOCIAL DETERMINANTS OF HEALTH COMMON DATA ELEMENTS. SO ENHANCING AND INTEGRATING THOSE DATA, MAKING THEM MORE INTRAOPERABLE ACROSS NOT JUST SCHARE BUT ACROSS NIH PLATFORMS AND PUSHING THESE OUT THROUGH THE NAIRR IS A GOAL OF WHAT WE'RE DOING IN AI. WE'VE DONE A LOT HERE AT NIH, AND THE NEXT SLIDE SORT OF HIGHLIGHTS SOME OF THE ACTIVITIES. YOU'VE SEEN THAT EVERYTHING I PRESENTED HAS HAPPENED SINCE 2019. IT'S A TREMENDOUS AMOUNT OF WORK. WE ARE NO EARLY BIRDS TO AI, WE ARE AT THE CUTTING EDGE. THERE'S STILL MORE THAT WE CAN DO. WE CERTAINLY LACK THE SCALE OF DATA RESOURCES TO OPTIMALLY USE AI. YOU PROBABLY KNOW THAT GOOGLE JUST PUT OUT A LARGE LANGUAGE MODEL JUST RECENTLY. IT'S HUGE. LLAMA 4 IS COMING OUT PRETTY SOON. I THINK IT'S MAYBE JULY. WE NEED THAT DATA SKILL FOR BIOMEDICAL RESEARCHERS. WE NEED DATA THAT'S RELEVANT FOR INDIVIDUAL PATIENTS. WE NEED IT IN A TIMELY FASHION, AND WE NEED IT AT A QUALITY THAT WE JUST DON'T HAVE RIGHT NOW, THAT'S EXACTLY WHAT DR. BERTAGNOLLI WAS TALKING ABOUT JUST A MOMENT AGO. THAT DATA DRIVES INNOVATION, IT DRIVES TECHNOLOGY DEVELOPMENT, IT WILL ALLOW FOR NEW THERAPEUTICS, IT WILL HELP US THINK ABOUT PREVENTIVE METHODS AND MEDICINE AND IT WILL IMPROVE OUR CARE OF DELIVERY. WE ALSO NEED THAT DATA TO REALLY BE ACROSS THE UNITED STATES, NOT JUST INCLUSIVE OF PEOPLE LIKE ME, BUT INCLUSIVE OF PEOPLE WHO LIVE IN RURAL ENVIRONMENTS, WHO ARE ELDERLY OR PERHAPS YOUNG, ADOLESCENTS, THEY NEED TO -- WE NEED TO REALLY THINK ABOUT WHAT IT LOOKS LIKE TO CREATE AI WITH HEALTH DISPARITIES IN MIND, AND ALSO WITH DISABILITIES IN MIND. AI IS PARTICULARLY CHALLENGED WHEN IT COMES TO DEVELOPING MODELS OF DISABILITIES. WE INTEND TO AND WE MUST RESPECT AND ENGAGE PEOPLE AND EARN TRUST WHEN WE'RE THINKING ABOUT ARTIFICIAL INTELLIGENCE. AND THAT MEANS THAT DIVERSITY IS CRITICAL. WE OF COURSE WISH TO PROMOTE HEALTH WITHIN OUR POPULATION SO WE NEED TO DRAMATICALLY INCREASE THE DATA COLLECTIONS FROM OUR CLINICAL CARE ENVIRONMENT TO INCLUDE ALL POPULATIONS AND TO FACILITATE AN OPTIMAL AND ETHICAL USE OF AI. THIS IS MY CALL TO YOU. I'M ASKING YOU TO THINK ABOUT A NEW FIELD OF SCIENCE IN ETHICAL AI THAT REALLY EMBEDS DIFFERENT TYPES OF TRAININGS AND LEARNINGS WHEN WE'RE THINKING ABOUT BIOMEDICINE AND APPLICATIONS TO HEALTH, I THINK THAT IT SHOULDN'T BE BUSINESS AS USUAL. I THINK WE REALLY NEED TO THINK DEEPLY ABOUT WHAT ARE SOME OF THE NEW SCIENCES THAT CAN UTILIZE NEW OPPORTUNITIES IN AI, BUT PUSH IT FORWARD IN BIOMEDICINE. SO WITH THAT, I AM GOING TO TURN IT OVER TO DR. TABAK FOR THE NEXT AND LAST SLIDE. >> THANKS VERY MUCH. AND SO WITH THAT BRIEF BUT VERY COMPREHENSIVE OVERVIEW OF WHAT'S BEEN GOING ON AT NIH RECENTLY, WE OFFER THE FOLLOWING PROPOSED CHARGE FOR AN AI WORKING GROUP. THE GROUP WOULD BE CHARGED WITH ARTICULATING A STRATEGIC AND INTEGRATED VISION OF BIOMEDICAL RESEARCH OPPORTUNITIES THAT WOULD BENEFIT FROM DEVELOPING AN APPLICATION OF NOVEL AI METHODS, CONSIDERING THIS CHARGE, THE AI WORKING GROUP'S RECOMMENDATIONS SHOULD ADDRESS THE FOLLOWING THREE POINTS. FIRST, ASSESS PROGRESS TO DATE AND DEVELOP A FRAMEWORK TO SUPPORT STRATEGIC PRIORITIES AND BIOMEDICAL RESEARCH OPPORTUNITIES IN AI. PARTICULARLY INVOLVING THE DEVELOPMENT AND APPLICATION OF NOVEL METHODOLOGIES, FOREKNOWLEDGE DISCOVERY AND HUMAN HEALTH. THIS SHOULD INCLUDE THE NECESSARY DATA AND COMPUTING RESOURCES THAT WILL BE REQUIRED FOR USING AND SCALING AI IN BIOMEDICINE, ALLOWING FOR INTERDISCIPLINARY COLLABORATION ACROSS FIELDS. SECOND, WITH RESPECT TO THESE PRIORITIES, DEFINE THE POTENTIAL PRIVACY, SECURITY, ETHICAL, POLICY AND COST CHALLENGES THAT NIH SHOULD CONSIDER IN SUPPORTING AND DEPLOYING AI TO MAXIMALLY BENEFIT THE BIOMEDICAL ENTERPRISE. CONSIDER POTENTIAL APPROACHES FOR MITIGATING THESE CHALLENGES, INCLUDING NEW AREAS OF SCIENCE THAT COULD BE DEVELOPED. AND THEN FINALLY, RECOMMEND STRATEGIES FOR ENSURING EQUITABLE BENEFITS RESULT FROM THESE STRATEGIC PRIORITIES INCLUDING EQUITABLE BENEFITS IN INCLUSIVE ALGORITHMIC DEVELOPMENT, THE APPLICATION OF TRANSPARENT AND EXPLAINABLE AI, AND COLLABORATIVE TRAINING PROGRAMS TO ENABLE A HEALTH LEARNING ENVIRONMENT USING AI AND AI-ENABLED TOOLS. THREE POINTS, BUT LOADED THREE POINTS, AND WITH THAT, WE CAN OPEN IT FOR SOME QUICK DISCUSSION BEFORE DR. BERTAGNOLLI WOULD CALL THE QUESTION. SO COMMENTS OR QUESTIONS? >> I CAN COMMENT ON THE ACD AND AI HAPPENING JUST BEFORE GENERATIVE AI CAME ABOUT. AND THEREFORE, YOU KNOW, UPDA UE IS DEFINITELY NECESSARY SO THAT IS COVERED IN THE NEW CHARGE, VERY EXCITING TIME. >> GREAT, THANK YOU. I GUESS I SHOULD HAVE MENTIONED, I THINK WE HAVE FOUND SOMEONE -- TO THE ACD, SO THANK YOU FOR AGREEING TO BE AT LEAST ONE PERSON. >> YOU KNOW, I JUST -- I WOULD LIKE TO ADD, WE UNDERSTAND THAT OUR BIGGEST -- ONE OF OUR BIGGEST -- I MEAN, THIS IS ABOUT AI, BUT WHAT WE'RE LOOKING FOR, TOO, IS ALSO THE DATA WE NEED TO DELIVER. IN ADDITION TO HOW DO YOU USE THESE TOOLS. SO IT'S NOT JUST, WELL, WE HAVE THESE TOOLS NOW, FIND THEM AND USE THEM. IT'S ABOUT WHAT DATA DO WE NEED TO DELIVER. SO I'M THINKING OF THE NEW PRIMARY CARE NETWORK, RIGHT? WHY ARE WE GOING INTO THESE REALLY CHALLENGING COMMUNITIES? WE'RE GOING BECAUSE THAT'S WHERE PEOPLE NEED US, BUT WE'RE ALSO UNDERSTANDING THAT THESE KINDS OF TECHNOLOGIES, I THINK ARE GOING TO HELP US SO MUCH BE THERE TOO. SO PROPERLY UNDERSTANDING HOW TO RESOURCE AND BE ABLE TO DELIVER THOSE DATA FROM THOSE ENVIRONMENTS IS ALSO A LITTLE BIT ABOUT THIS CHARGE. WHAT DATA DO WE NEED AS WELL AS HOW WOULD AI BE DEPLOYED. TEST TEST TEST I WANT TO THANK SUSAN FOR THE GREAT DEAL OF ATTENTION TO THE ETHICS AND SECURITY AROUND ALL OF THIS, THE DATA AND THAT APPLIES TO THE PREVIOUS CONVERSATION,A ROUND THE LIBRARY AND THE DATA AS WELL EMPLOY REALLY IMPORTANT AND REALLY APPRECIATE IT AND THE IDEAS YOU HAVE AROUND IT OR REALLY TERRIFIC, THANK YOU. HARD TO HAVE ANYTHING MORE BUT THE AI PROBLEM AND CHALLENGE DOES GO BEYOND THE FUNDAMENT AMILLIO METHODS, FAIR AND EQUALLY DIVERSE DATA SETS AND CERTAINLY REACHES THE USERS, I THINK WE'RE ALREADY PERHAPS AT A POINT WHERE WE HAVE MORE DATA SETS THAN ACTUAL BIOMEDICAL AI PRACTITIONERS AND 1 IS GROWING LINEARLY, AND 1 EXPOTENTIALLY, THE DATA SETS, AND THIS FALLS BETWEEN AN NSF AND NIH PROBLEM, WHERE WE NEED NEW METHODS AND PRACTITIONERS AND THAT GAP IS WIDENING WAY TO UNCOMFORTABLY, I'M REALLY TBLAD WE CAN START TO NARROW THAT GAP BETWEEN THESE 2 FIELDS. >> YES, PLEASE, BRIAN. >> FOCUS ON THE DATA GENERATED, I WONDER ABOUT THE WAYS AI MIGHT HELP WITH MANAGING RESEARCH ACTIVITIES AS WELL, SO WHEN YOU'RE DOING A MULTISITE TRIAL, THAT HAS A LOT OF COMPLEXITY, HOW DO YOU TRACK PARTICIPANTS THROUGH ENROLLMENT WITH WHO ARE MORE ENGAGING WITH THE PARTICIPANTS AND ALLOW THEM TO UNDERSTAND THEIR ROLE IN THE PROJECT AND WHEN THEY NEED TO IN AND ALL THE OTHER INVESTIGATORS INVOLVED AND YOU KNOW THE RESEARCH IS MORE AND MORE COMPLEX, THERE'S MORE REGULATION THAT PIs HAVE TO MANAGE AND SO THE EXTENT TO WHICH AI CAN HELP WITH RESEARCH ACTIVITIES AS WELL AS DATA THAT ULTIMATE LE COMES WILL BE GOOD TO HAVE AS PART OF THE CHARGE. >> THAT IS A REALLY GREAT IDEA THAT I HADN'T THOUGHT ABOUT, SO THANK YOU VERY MUCH FOR THAT 1. BECAUSE THAT WILL TAKE CONCERTED EFFORT IF WE'RE GOING TO DEVELOP TOOLS THAT HELP US TO DO BETTER RESEARCH, SO THANK YOU FOR THAT. >> GOOD POINT. AND INDEED, I'LL TELL YOU THAT MANY OF THE INSTITUTES AND CENTERS HAVE ADOPTED THOSE TYPES OF EFFORTS AND OF COURSE THEY ARE VERY WILLING TO SHARE ACROSS THE AGENCY, SO THEN 1 GROUP DEVELOPS AND THEN EVERYBODY ELSE OBVIOUSLY BENEFITS BUT THANK YOU FOR ARTICULATING THAT. HOWARD, YOU HAVE A COMMENT OR QUESTION? NYES INDEED, SO THIS AI WORKING GROUP AND VERY TIMELY, I IT'S REALLY FANTASTIC AND REALLY A RAPIDLY GROWING TREND, 1 OF THE NEW DIVIDES THAT'S EMERGING IS SOME OF THE COMMERCIAL AI MODELS ARE ACTUALLY THINKING ABOUT FOR EXAMPLE, THE RECENT ALPHA FOLD 3 FROM GOOGLE, THE UNDERLYING MODEL IS NOT PUB LIKELY ACCESSIBLE. SO WE MAY REALLY SOON HAVING PEOPLE USING THESE TOOLS. THEY WILL END UP IN THE LITERATURE, SO IT GOES BACK TO THE NLM CONVERSATION, BUT IT'S ACTUALLY A BLACK BOX RIGHT? AND SO I THINK THE EMPHASIS ON ETHICS AND ACCESS AND FAIR USE IS VERY IMPORTANT GOING FORWARD. >> ABSOLUTELY, THANK YOU VERY MUCH FOR THAT AS WELL. THIS HAS BEEN A PROBLEM ACTUALLY THIS HAS BEEN A PROBLEM WE'VE ALREADY HAD WITH FOR EXAMPLE, DATA FROM THE CLINICAL CARE ENVIRONMENT WHICH HAS BEEN WAY TOO MUCH OF A BLACK BOX WITH CURATED DAILY BASIS--DATA SETS FOR INSTANCE AND THERE HASN'T BEEN ENOUGH ATTENTION THAT YOU WOULD NEVER DELIVER A RESULT OR BELIEVE A RESULT UNLESS YOU KNEW YOU COULD DIVE THOROUGHLY INTO THE DATA THAT WAS USED TO GENERATE IT AND THAT NEEDS TO BE 1 OF THE GUIDING PRINCIPLES HERE. >> OKAY, I THINK THE TIME HAS COME. >> SO LET ME THEN CALL THE QUESTION. DO I HEAR A RECOMMENDATION TO ENDORSE CREATION, A MOTION TO ENDORSE CREATION OF THIS NEW WORKING GROUP. OKAY, AND THE SECOND, I THINK I GOT BOTH, ANY FURTHER DISCUSSION? OKAY ALL IN FAVOR SAY AYE AND RAISE YOUR HAND. >> AYE. >> ANY OPPOSED? OKAY, WELL, THERE WE GO. WE GOT A NEW WORKING GROUP. THANK YOU VERY MUCH. AND WITH THIS, I THINK THIS BRINGS OUR MEETING TO A CLOSE, I JUST HAVE TO SAY A FEW WORDS AS WE END HERE. WE'VE TRIED TO GIVE YOU A LOOK AT SOME OF THE INNOVATIVE SCIENCE THAT'S GOING ON. WE'VE TRIED TO GIVE YOU A LOOK AT INFRASTRUCTURE NEEDS THAT WE THINK ARE REALLY IMPORTANT, EXCITING AND NEW AND THAT WE'RE MOVING FORWARD WITH AND I HOPE WE'VE GIVEN YOU A VIEW THAT WE INTEND TO BE BOLD AND DO SOME THINGS THAT PEOPLE NEED. WHY? BECAUSE PEOPLE NEED US TO STEP UP AND TO TAKE LEADERSHIP IN SOME REALLY CRITICAL AREAS THAT I DON'T THINK ANYBODY ELSE, I DON'T THINK ANY ORGANIZATION BUT THE NIH CAN REALLY TAKE THE LEADERSHIP HERE. SO IT'S REALLY INCREDIBLY HELPFUL AND WE SO APPRECIATE YOUR SUPPORT AND INPUT INTO THIS. I WILL REMIND YOU THAT IF ANYTHING, IF YOU THINK OF ANYTHING LATER, WE'RE ALL HAPPY TO HEAR COMMENTS IF YOU THINK ABOUT THEM LATER BECAUSE YOUR INPUT INTO THIS IS ABSOLUTELY CRITICAL, WE COULDN'T DO ANY OF--ANYTHING THAT WE DO ESPECIALLY NOT IN A NEW BOLD INITIATIVES WITHOUT THE REALITY CHECK WE GET FROM OUR ACD, SO SO MUCH APPRECIATE THAT. I WANT TO THANK EVERYBODY WHO WAS INVOLVED IN PULLING OFF TODAY'S MEETING, IT REALLY DOES TAKE A HUGE TEAM TO MAKE SURE THAT EVERYTHING GOES SMOOTHLY AND WE'RE SO GRATEFUL, THANKS TO LARRY FOR HIS PIVOTAL ROLE IN ORGANIZING AND CO LEADING, ACTUALLY ORCHESTRATING THE MEETING AND I ALSO WANT TO SHARE MY THANKS TO THE PRESENTERS FOR SHARING THEIR IMPORTANT TOPICS, CERTAINLY ALL OF THE ACD MEMBERS FOR GIVING US YOUR VALUABLE FEEDBACK AND INSIGHT AND TIME, AND FINALLY ALL THE OTHER PEOPLE WHO WORKED BEHIND THE KEENS INCLUDING THE TEAM FROM THE IMMEDIATE OFFICE, CINDY, JACQUELINE, AND TYROAN, THE VIDEOCAST TEAM, ASL INTERPRETERS AND CONTRACT SUPPORT, PARTICULARLY KARLY SULLIVAN AND JORDAN [INDISCERNIBLE]. AND LAST I WANT TO THANK EVERYONE ELSE WHO TUNED IN OVER THE PAST 2 DAYS. WE ALSO VERY MUCH APPRECIATE YOUR INTEREST AND INVOLVEMENT IN WHAT WE'RE DOING AT NIH. SO THANK YOU ALL SO VERY MUCH AND WITH THAT, I'M GOING TO HIT THE GAVEL AND SAY WE'RE ADJOURNED. THANK YOU.