>> GOOD MORNING, WELCOME BACK TO THOSE WHO WERE HERE YESTERDAY. WELCOME TO THOSE JOINING US TODAY. I'M STILL GETTING USED TO HOW WE SWITCH WHERE PEOPLE ARE. WE'LL FIGURE THAT OUT. TODAY WE'RE GOING TO SWITCH A LITTLE BIT FROM SOME OF THE TOPICS WE WERE TALKING ABOUT YESTERDAY AND LOOK AT DIFFERENT KINDS OF OUTCOMES RELATED TO TECHNOLOGIES. AARON WILL BE OUR FIRST MODERATOR. LEAVE IT UP TO YOU TO INTRODUCE YOURSELF AND SPEAKERS. >> THANK YOU, THANKS EVERYONE FOR COMING BACK BRIGHT AND EARLY THIS MORNING. MY NAME IS AARON SPANEIL HEALTH SCIENCE POLICY ANALYST AT NIH. I WAS PREVIOUSLY AT OFFICE OF BEHAVIORAL SOCIAL SCIENCES WITH MY COLLEAGUES HERE. I'M NOW IN THE IMMEDIATE OFFICE OF DIRECTOR WORKING ON HEEL INITIATIVE, HELPING TO END ADDICTION LONG TERM INITIATIVE. HEAL. MY BACKGROUND IS IN OCCUPATIONAL THERAPY AND NEUROREHABILITATION AND ASSISTIVE TECHNOLOGY WHICH IS WHY I'M VERY EXCITED FOR THIS NEXT PANEL WHERE WE WILL BE FOCUSING ON THE USE OF TECHNOLOGY TO INFORM PAIN OUTCOMES. YESTERDAY WE SPENT A LOT OF TIME TALKING ABOUT THE SHORTCOMINGS OF THE ONE TO TEN PAIN SCALE. THERE'S A RELIABILITY ISSUE, ESPECIALLY IN CASES WHERE PEOPLE ARE NON-VERBAL OR UNABLE TO EXPRESS THEIR PAIN BECAUSE OF A MEDICAL CONDITION OR LANGUAGE BARRIER. IT JUST MAKES YOU THINK WOULDN'T IT BE BRAT IF TECHNOLOGY COULD AUGMENT OR SUPPORT SOME OF THE MEASURES WE CURRENTLY HAVE. OUR PANEL WILL FOCUS JUST ON THAT. I WOULD LIKE TO INTRODUCE FIRST DR. KAREN LOMOND. SHE WILL BE OUR FIRST SPEAKER. DR. LOMOND IS A BIOMECHANICKIST TRAINED IN MOTION CAPTURE AND MOVEMENT ANALYST WHO STUDIES INFLUENCE OF CHRONIC PAIN, MOVEMENT PATTERNS FOR THE LAST TEN YEARS. IN HER WORK SHE CONTRIBUTES TO SURFACE EMG DATA TO STUDY UNDERLYING HAS BEEN RENT MOVEMENT, ASSOCIATED WITH VARIOUS MUSCULOSKELETAL DISORDERS AND INJURY, PRIMARILY CHRONIC BACK PAIN. RECENTLY SHE BEGIN TO EVALUATE EFFECTIVENESS IN DETECTING MOVEMENT AND BALANCE RELATED IMPAIRMENT IN PERSONS WITH LOW BACK PAIN IN HOPE TO IMPROVE TARGET TREATMENT OUTCOMES. THANK YOU VERY MUCH. >> THANK YOU. HANKS TO THE ORGANIZERS FOR INVITING ME HERE, I LOOK AROUND THE TABLE AND A LITTLE HUMBLED TO BE A INCLUDED IN MISGROUP. I DON'T TYPICALLY CONSIDER MYSELF A TRADITIONAL PAIN RESEARCHER, THOUGH I WORK WITH CHRONIC PAIN POPULATIONS FOR MOST OF MY CAREER BUT WHAT I AM IS SOMEBODY WHO ENJOYS PUSLESS AND BREAKING DOWN WHERE OUR PATHOLOGICAL MOVEMENTS WHICH PORTIONS OF PATHOLOGICAL MOVEMENTSES MAYBE ASSOCIATED WITH DISEASE OR PAIN STATE AND WHICH AREN'T, HOW WE CAN THEN TARGET TARGET THOSE INTERVENTIONS SO I SPENT THE BULK OF MY CAREER IN PHYSICAL THERAPY AT UNIVERSITY OF VERMONT, CENTRAL MICHIGAN AND NOW COLLEGE PHYSICAL THERAPY DEPARTMENT. SO I MAKE THIS DISCLAIMER ALL THE TIME, I'M NOT ACTUALLY A PHYSICAL THERAPIST, I WORK WITH THEM. SO I CANNOT TREAT YOUR CHILDREN NECK PAIN, I GET THAT A LOT, LET'S GET THAT OUT OF THE WAY EARLY. MY TALK I TOOK A BRIEF SUGGESTED TITLE LITERALLY AND WHEN I WAS ASKED TO TALK ABOUT WEARABLES IN REHABILITATION SETTINGS I LOOKED DOWN THE AGENDA AND SAW FIRST AND MANY OTHERS COMING, DAVID WILL TALK BIOMARKERS AND LOW BACK PAIN TO I TRIED TO TAILOR MY TALK TO THE DAY AND REALLY GIVE A SENSE OF WHAT IS AVAILABLE IN MARKET FOR MEASURING FUNCTIONAL OUTCOMES HOW THEY MAY RELATE TO PAIN. SO I'LL TALK ONE TOKEN SLIDE ON PAIN SPECIFICALLY IN THE PRESENTATION, I WILL SHOW YOU EXAMPLESES THAT RELATE TO PAIN AS WELL. SO WE'LL TALK ABOUT THE ROLE OF (INAUDIBLE) VERY CHALLENGING TO WORK WITH, ISLE SHOW YOU SOME OF THE CURRENT TECHNOLOGIES IN ACCELEROMETERS AND IMUs, TALK TO A FEW PRIMARY CLINICAL APPLICATIONS THAT RELATE SPECIFICALLY TO PAIN AND THAT I THINK AT LEAST RELATES SPECIFICALLY TO PAIN. I WILL TOUCH ON SOME EMERGING TECHNOLOGIES AND WHERE THE FIELD MAY BE GOING AND HAVE SOME INSIGHT TO SOME OF THE PROBLEMS YOU ALREADY PULLLY DOES CUSSED AND TALK ABOUT -- DISCUSSED AND HOW WE CAN TALK ABOUT COMPLETE INTEGRATION. THAT'S THE PLAN FOR THE DAY. AS I SAID, I DO MOST OF MY WORK IN THE PHYSICAL THERAPY WORLD WORKING WITH PHYSICAL THERAPISTS AND SO IN THAT WORLD AND IN THE REHABILITATION WORLD IN GENERAL WE THINK ABOUT THE PHYSICAL PERSON AND PHYSICAL FUNCTION OF THE PERSON SO FOR ANYONE MEASURING PAIN, IT IS GENERALLY PAIRED WITH SOME FUNCTIONAL MEASURE. SOP I'M USED SEEING PATIENT WHOSE COME TO CLINIC, SEEK TREATMENT, THEY ARE IN A HIGHER PAIN STATE AND RELATIVELY LOW FUNCTIONAL STATE FOR WHATEVER CONDITION THEY ARE IN. SO THE GOAL OF THE CLINICIAN IS WORK WITH IS TYPICALLY TO IMPROVE FUNCTION AND THE HOPE IS THAT PART AND PARCEL WITH THAT WE WILL SEE REDUCTIONS IN PAIN. CERTAINLY PHYSICAL HER MISTAKING GOOD STRIDES TO START TO LOOK AT PATIENT AS A WHOLE AND APPROACH FROM BIOPSYCHOSOCIAL MODEL BUT THE PRIMARY INTERVENTIONS ARE SOMEWHAT PHYSICAL AND YOU ARE DOING SOME OTHER THINGS LIKE SOME PATIENT EDUCATION, GRADED EXPOSURE THERAPY, SO CERTAI LEISTERING TO TRY TO ADDRESS PSYCHOSOCIAL FACTORS BUT ROOM FOR IMPROVEMENT THERE. WE KNOW SOME CONDITIONS IN PARTICULAR TALK ABOUT NEUROMUSCULAR AND MUSCULOSKELETAL CONDITIONS TODAY IN PARTICULAR AS EXAMPLES WHICH MAY OR MAY NOT BE TRADITIONAL PAIN POPULATIONS BUT JUST TO GIVE YOU A SENSE OF WHAT WE CAN AND CAN'T MEASURE, I WILL HIGHLIGHT WHERE SOME OF THESE IMPAIRMENTS ARE ACTUALLY VERY SIMILAR TO SOME MORE TRADITIONAL PAIN POPULATIONS. I WILL USE AN EXAMPLE OF CHRONIC LOW BACK PAIN, AN ISSUE NEAR AND DEAR TO MY HEART, I GOT INTO THIS BUSINESS BECAUSE MY MOM WAS CHRONIC PAIN PATIENT WITH LOW BACK PAIN AND IT'S REALLY RICH AREA FOR STUDY, COMPLEX PROBLEM SO TICKLES THAT PART OF MY PSYCHE AS WELL TO SOLVE PROBLEMS. BUT BACK PAIN IN PARTICULAR IS THAT IT'S A PROBLEM THAT AFFECTS 85% OF THE AMERICANS AND HIGHLY RECURRENT SO WHEN YOU TO TREATMENTS PARTICULAR LIPPIESCAL THERAPY AND SHOW IMPROVED FUNCTION REDUCTION IN PAIN, WE OFTEN CAN'T MEASURE DIFFERENCE BETWEEN DIFFERENT TYPES OF PHYSICAL THERAPY INTERVENTIONS BECAUSE WE THINK POPULATIONS ARE HETERO GENIUS SO SUBGROUPING TO BETTER TARGET TREATMENT BUT STILL DESPITE EFFORTS THE PROBLEM COMES BACK AGAIN AND AGAIN SO MANY MONTHS OR YEARS SO THE ISSUE IN THE FIELD I THINK IS ONE WHERE WE HAVE FUNCTIONAL MEASURES WE ARE TARGETING AND WE HAVE MAY NOT BE DIRECTLY LINKED TO THE PAIN EXPERIENCE AS WE THINK SO WILL'S WORK TO BE DONE. WEARABLE SENSORS IS INTRIGUING TO TACKLE THIS PROBLEM BECAUSE THEY GIVE US DIRECT MEASURE OF FUNCTION, WHEN I SAY FUNCTION IT'S MOTION, WHEN THE MOTION OCCURS TOO MUCH OR TOO LITTLE. THOSE KINDS THINGS AND SOME INSIGHT IN NEURAL CONTROL OF MOTION. AND HOW WE PLAN MOVEMENTS PREPARE FOR MOVEMENTS AND BY USING THESE SENSORS IN MORE ECOLOGICAL CONDITIONS AND OUT IN THE WORKPLACE RATHER HE THAN JUST CLINIC WE CAN GET A BETTER SENSE OF HOW MOTION IS ALTERED AND MAKE A LONGER MORE LASTING IMPACT ON THAT MOTION. SO WE HAVE SEEN A LOT OF EXAMPLES OF WEARABLE SENSORS SO I WILL PUT THE SLIDE UP TO GIVE A SENSE OF OVERALL THESE ARE THE KINDS OF THINGS WE CAN MEASURE. WE TALK ABOUT THE SMART WATCH INTERVENTIONS AND BASIC ACTIVITY RACING, I'LL SPEND TIME TODAY FOCUSING ON HOW WE CAN MEASURE ASPECTS OF MOVEMENT PRIMARILY TALK ABOUT THE MOST FUNCTIONAL BIGGEST FUNCTIONAL ACTIVITY PHYSICAL THERAPISTS START TO DEAL WITH, TALK ALSO ABOUT TIMED UP AND GO SO STANDING FROM A CHAIR WALKING, THOSE SORTS OF REALLY BASIC FUNCTIONAL ACTIVITIES THAT GET YOU LIE THE DAY. THROUGH THE DAY. WE LIKE THE SENSORS THEY HAVE GOTTEN CHEAP, RELATIVELY DISCRETE, PROBABLY HAVE THE ROOM IS WEARING AN APPLE WATCH OR SOMETHING LIKE THAT, VERY UBIQUITOUS IN THE MARKETPLACE AND THEY ALWAYS GET EVERYBODY FROM SEVERE MOBILITY IMPAIRED TO ELITE ATHLETES AND TRACK WHAT THEY ARE DOING IN A RELATIVELY ECOLOGICAL ENVIRONMENT AS THEY GO ABOUT THEIR DAY GIVING MORE OPTIONS FOR DATA COLLECTION. THE TECHNOLOGY I'LL FOCUS ON THE MOST AND WILL SET UP DAVID'S TALK THIS AFTERNOON IS TECHNOLOGY THAT IS INCORPORATION OF LEE TYPES OF SENSORS. AND THIS IS SOMETHING THAT YOU ARE INHERENTLY FAMILIAR WITH, THEY LIVE INSIDE YOUR CELL PHONE, PROBABLY IN YOUR POCKET OR BAG RIGHT NOW. SO THEY ARE GYRO SCOPES WHICH SHOW ANGULAR VELOCITY, MULTIPLE DIRECTIONS SO BASICALLY GIVING MEASURE OF ROTATION, LINEAR ACCELEROMETERS WHICH AGAIN IN MULTIPLE DIRECTIONS TELL US ABOUT LINEAR ACCELERATION AND THESE AS YOU CAN SEE EACH HAVE SOME ADVANTAGES AND DISADVANTAGES, ONE OF THE BIG ISSUES IN TERMS OF ACCELEROMETERS IS THE IDEA OF SIGNAL DRIFT BECAUSE THEY ARE QUITE SUSCEPTIBLE TO INFLUENCE OF GRAVITY SO WE COMBINE WITH THE GYRO SCOPE AND IT GIVES YOU A COME PASS HEADING TO HELP UNDERSTAND THE INFLUENCE OF GRAVITY AND TOGETHER THEY CAN ACTUALLY COMBINE INTO ONE SENSOR REFERRED TO AS IMU OR INERTIAL MEASUREMENT UNIT. THERE'S COULDN'TLESS EXAMPLES ON THE MARKET PACKAGED FOR VERY SPECIFIC TASKS, ANYTHING FROM -- THERE'S A COMPANY THAT DOES ONE THAT SITS IN A SLEEVE ON THE ELBOW THAT MEASURES DURING PITCHING AND THROWING MOTIONS, TO A SYSTEM LIKE THIS THIS IS ONE I WORKED WITH QUITE A BIT, IT'S A (INAUDIBLE) GROUP OUT OF OREGON AND IT'S CLINICAL SYSTEM SO YOU HAVE ANYWHERE FROM 4 TO 8 SENSORS, AS A RESULT A FULL BODY, WHEN SHE HAS DONE IS GREAT STRIDES INSTRUMENTING THE ASSESSMENTS IN PARKINSON, I'LL SHOW YOU THAT DATA IN A MINUTE AS WELL. AGAIN, THERE ARE MANY VERSIONS OF THESE, NOT ENDOSERMENT OF ANY ONE PARTICULAR SYSTEM BUT JUST ONE EXAMPLE KIND OF WHAT THEY LOOK LAKE AND HOW HEADACHE BE USED. SO LET'S -- HOW THEY CAN BE USED. LET'S LOOK AT CLINICAL APPLICATIONS, THIS LIST IS NOT EXHAUSTIVE, I HAD A LIST OF SEVEN OR EIGHT SOY WHITTLED IT DOWN SO I WHITTLED IT DOWN TO THIS MEETING. THE FIRST ARE ASSESSMENT BASED AND LAST IS BIOFEEDBACK IS MORE TREATMENT BASED THOUGH YOU CAN ARGUE ALL HAVE PATIENT IN TREATMENT. SO I WILL GO THROUGH THOSE RELATIVELY EFFICIENTLY TO SEE WHAT EACH DOES. WE HAVE GOTTEN TO THE POINT OF SUFFICIENT DATA ANALYSIS TECHNIQUES AND MATHEMATICAL TECHNIQUES TO TAKE THIS RAW ANGULAR ACCELERATION AND LINEAR ACCELERATION DATA AND GET MEANINGFUL NUMBERS FOR THE CLINICIAN. WHICH CAN HELP US HOPEFULLY PROVIDE MORE DETAIL SENSITIVE OUTCOME MEASURES. I WENT TO PHYSICAL THERAPY WHERE STANDARD FIELD SOMETHING I TOLD MY STUDENTS I CALL IOMETRY OR VISION IF YOU HAVE BEEN BEEN TO A PHYSICAL THERAPIST THE FIRST IS YOU WATCH YOU MOVE. MUCH DATA COLLECTION IS SIMPLE OBSERVATION. SO I WILL SHOW YOU EXAMPLES AS WE GO FORWARD WHERE WE DON'T -- THERE'S A LOT OF SOFT TISSUE MOVEMENT THAT HAPPENS TO UNDERSTANDING WHAT'S HAPPENING AT JOINT OVERALL TISSUE IS A COMPLEX TASK AND NOT FAIR OF US TO ASK CLINICIANS TO MAKE SENSITIVE JUDGMENTS SO THERE IS A ROLE FOR THIS TECHNOLOGY AND HELPING TO AID SOME OF THAT CLINICAL DECISION MAKING AND CLINICAL EXAMPLE. SO JUST AN EXAMPLE OF THE PROTOCOL BASIC FUNCTIONAL MOW BUILT FORWARD RISK ASSESSMENT SO HAPPENS IN A WIDE VARIETY OF POPULATIONS FROM LOW BACK PAIN TO PARKINSON TO STROKE AND BASICALLY IF YOU HAVEN'T SEEN IT BEFORE YOU HAVE SOMEBODY SIT IN A CHAIR WITH ARMS THEY STAND UP, THEY WALK A SET DISTANCE ABOUT THREE METERS, THEY TURN BACK AND SIT DOWN. THE CLINICIAN WATCHES ANT OBSERVES BUT PRIMARY OUTCOME MEASURE IS A SOP WATCH, HOW LONG DOES IT TAKE YOU TO DO THIS. THERE'S REASONABLE DATA THAT SHOWS YOU CAN SORT OF TALK ABOUT THERE'S NO IMPAIRMENT, MODERATE IMPAIRMENT, MODERATE TO SEVERE IMPAIRMENT AND PUT PEOPLE IN BOXES BASED ON THIS. SO YOU SEE WE CAN INSTRUMENT THIS TEST AND USE ACCELERATION DERIVED MEASURES FROM THESE IMUs THAT CAN PREDICT BETTER THAN TOTAL TIME. WHICH TELLS US THAT CLINICIANS MAY BE MISSING VALUABLE INFORMATION, MAYBE MOVEMENT IMPAIRMENTS IN SOME OF THESE PATIENTS THAT WE ARE NOT ABLE TO ASSESS USING THESE OLD SCHOOL STOPWATCH TECHNIQUES SO WE CAN DIG DEEPER TO THAT ACCELEROMETER DATA AND FIND THOSE IMPAIRMENTS EARLIER AND TARGET TREATMENTS THERE. SIMILARLY, I DID A STUDY WITH MULTIPLE SCLEROSIS PATIENT, NOT A PAIN POPULATION BUT THE IDEA IS SIMILAR WHERE WE DID A FULL BALANCE AND DATA ASSESSMENT USING IMUs AND IN PARTICULAR LOOK AT POSTURAL -- STANDARD STANDING FOR 30 SECONDS EITHER ON OR OFF SURPASS TO CHANGE THE SOMATOSENSORY INPUT. WE FOUND SOME OF THOSE POSTURAL IMPAIRMENTS WERE MORE SENSITIVE TO IDENTIFYING MOVEMENT IMPAIRMENT IN PEOPLE WITH MS THAN WHAT'S STANDARD FOR THE FIELD WHICH IS 25-FOOT WALK TEST. 25-FOOT WALK TEST IS WHAT IT SOUNDS LIKE, PATIENT WALKS 25 FEET AND YOU TIME HOW LONG IT TAKES AND AGAIN PEOPLE INTO A BUCKET THERE WITH NORMAL RANGE, THEY HAVE A SLIGHT IMPAIRMENT, MODERATE TO SEVERE IMPAIRMENT. SO AGAIN GIVING US MORE GRANULARITY IN TERMS OF UNDERSTANDING WHAT'S HAPPENING IN A PARTICULAR PATIENT. THESE BASIC, THE ABILITY TO STAND WITHOUT RISK OF FALL, THE ABILITY TO WALK AND TRAVERSE YOUR ENVIRONMENT WITHOUT RISK OF FALL. THESE ARE THE MOST BASIC OF FUNCTIONAL ACTIVITIES SO IMPORTANT PLACE TO LOOK FOR GOING FORWARD. WE CAN ALSO IDENTIFY PATHOLOGICAL MOVEMENT PATTERNS, THIS IS SOMETHING NEAR AND DEAR TO MY HEART FOR BACK PAIN FOR SURE. MANY CONDITIONS NOT JUST LOW BACK PAIN ARE HIGHLIGHTED BY MOVEMENT IMPAIRMENT OR HAS BEEN RENT MOVEMENT PATTERNS DEPENDING WHO READS THE LITERATURE. SO THE ABILITY TO MORE CLOSELY ANALYZE AND MEASURE WITH GREATER PRECISION CAN HELP POTENTIALLY IDENTIFY MOTIONS ON SOONER AND TRACK THEM TO HELP US WITH EFFORTS ACTUALLY DOING WHAT WE WANT THEM TO DO. SO I USE THE EXAMPLE OF CHRONIC LOW BACK PAIN, THERE IS A SCHOOL OF THOUGHT NOT ENDOSING THIS BUT ONE TREATMENT APPROACH IS BASED ON WORK OF SHE SHIRLEY SIMON AND CHAMPIONING THIS WORK, SYSTEM IMPAIRMENT. BACK VERY EXPENSIVE HETERO GENIUS POPULATION. THE THOUGHT IS THAT CERTAIN SUBGROUPS OF PEOPLE WITH LOW BACK PAIN WITH SIMILAR MOVEMENT IMPAIRMENTS YOU MAYBE MORE LIKELY TO EXPERIENCE PAIN OR HAS BEEN RENT MOVEMENT PATTERNS FOR FLEXION OR EXTENSIONS BASED MOVEMENT, WE RYE TO PUT PATIENTS IN BUCKETS AND GIVE THEM EXERCISE TO IMPROVE MOTOR CONTROL AND STRENGTH TO STABILIZE THE SPINE IN THOSE PARTICULAR DIRECTIONS. SO AGAIN THIS IS BASED VERY MUCH ON CLINICIAN USING THEIR IOMETRY, THEIR VISION, SO IF WE WANT TO CATEGORIZE PEOPLE WE IMMEDIATE TO KNOW WHAT THE CLINICIAN IS SEEING IS IN FACT PATTERN THE PATIENT HAS SO WE SET OUT TO DO THIS USING MSI APPROACH UNIVERSITY OF VERMONT, THIS IS A BUSY SLIDE TO SHOW THIS IS ONE EXAMPLE SUBJECT NOT REPRESENTATIVE OF THE HOLD FIELD BUT A SENSE OF TWO ACTIVITIES FROM MSI EXAM, SO ON ALL FORCE LIFT THE IRON, NEW EXTENSIONS ON THE RIGHT SO EXACTLY WHAT IT SOUNDS LIKE. WE TRACK SIGNS AND SYMPTOMS, IT MAY OR MY NOT ELICIT A PAIN RESPONSE IN PATIENT. REPORTS PAIN WITH MOVEMENT. DURING THESE TASKS WE WILL SEE SOMEBODY WITH BACK PAIN, I WILL COME HERE AND HOPEFULLY VIDEO PEOPLE WILL FORGIVE ME SO ARM RAISE NORMALLY WHAT YOU BE ABLE TO LIFT THAT ARM FORWARD AND MAINTAIN A STABLE LUMBAR SPINE. (INAUDIBLE) ROTATION IMPAIRMENT LOW BACK PAIN THIS I SHOULD BE ABLE TO SIT AND NOT HAVE ANY SIDE (INAUDIBLE) LOW BACK PAIN, TEND TO SEE COMPENSATIONS SO THEY WILL TRY TO HAVE HAS BEEN RENT MOVEMENT PATTERNS WITHIN THE LUMBAR PELVIC REGION. THE CLINICIAN IS MEANT TO NOTE THESE, THE DIRECTION OF THE IMPAIRMENT AND WHETHER OR NOT ELICIT SYMPTOMS. CLINICIAN COMES IN, GIVES TACTILE FEEDBACK, AUDITORY QUEUES THINGS LIKE THAT. SAYS NOW PATIENT PRACTICE THAT AND THINK ABOUT DRAWING BELLY BUTTON INTO YOUR SPINE, SIT UP NICE AND TALL, STABILIZE THAT TRUNK REGION DOWN TO KNEE EXTENSIONS AND HOPEFULLY DO THE MOVEMENT WITHOUT HAVING COMPENSATION. DO YOU HAVE PAIN ON THIS MOVEMENT, IDEALLY USUALLY PATIENTS SAY NO, MY PAIN WENT AWAY AND SO WE TAKE THAT AS THAT'S A MOVEMENT THAT'S CONTRIBUTING TO THEIR PAIN. AGAIN ALL THIS IS RELYING ON CLINICIAN IDENTIFYING THE IMPAIRMENT, AND GIVING APPROPRIATE QUEUES. WHAT WE FOUND IN THIS STUDY, BLACK LINES ARE UNMODIFIED OR BASELINE CONDITION, THE GRAY ARE MODIFIED OR POST CLINICIAN INTERVENTION AND QUEUING. WE CAN SEE WE DIDN'T MAKE A BIG DIFFERENCE, IN PARTICULAR IF YOU LOOK AT T 12 L 1 THE UPPER LUMBAR SPINE IN CONDITION YOU SEE THE BIGGEST CHANGES WHERE WE STARTED TO DEFINITELY REDUCE MOVEMENT IN PARTICULAR IN THE FLEXION EXTENSIONS DIRECTION RIGHT HERE. WE GOT THEM BACK CLOSER AND TO ZERO SO THAT'S WHAT WE WANT TO SEE, THE SPINE NOT ROTATING OR NOT MOVING WHILE THEY ARE DOING LIMB MOVEMENTS. THE CLINICIANS REPORTED ROTATION BASED IMPAIRMENTS. THE DATA SHOW PARSING THROUGH IS MOST EXTRANEOUS MOVEMENT AND BIGGEST MOVEMENTS ARE FLEXION EXTENSIONS DIRECTION. THERE'S A FUNDAMENTAL INABILITY OR INACCURACY IN PERCEPTION OF MOVEMENT THAT MAYBE EFFECTING HOW BEDELIVER TREATMENT AND MAYBE CONTRIBUTING TO SOME OF THESE RESEARCH FINDINGS. AGAIN THIS IS EARLY DATA AND WE HAVEN'T PUBLISHED YET BUT CERTAINLY THERE'S SOME WORK TO DO ACROSS 20 PATIENTS WE LOOK AT, WE HATTED PERCENT AGREE WITH SENSOR AND CLINICIAN THAT RANGE ANYWHERE FROM 23 TO 85% SO QUITE A BIT OF VARIABILITY IN THAT DATA THAT WE NEED TO SORT OUT WHAT IS ACTUALLY HAPPENING. IF YOU THINK ABOUT RYING TO ASSESS LUMBAR SPINE MOVEMENT ALL OF THE FASCIA, ALL THE MUSCLES SUBCUTANEOUS TISSUE THAT SIT OVER TOP OF THAT SPINE, NO WONDER THAT CLINICIAN VERSUS A HARD TIME DETECTING THE SMALL RANGE OF MOTION. MANAGEMENT IS SOMETHING THAT PROBABLY DOESN'T CROP INTO YOUR MIND ADS ISSUE FOR PAIN PATIENTS BUT RISK IS ONE OF THE LEADING PREDICTORS OF DISABILITY AND ONE OF THE LEADING COSTS ASSOCIATED WITH DISABILITY IN AMERICA. WHETHER THROUGH STROKE OR AGING, AGING POPULATION IN THE U.S. IS WORTH CHATTING ABOUT. CHRONIC PAIN CAN BE -- ASSOCIATED WITH PAIN BEING A DISTRACTTOR AND HAVING ISSUES WITH THE COGNITION, THINGS LIKE THAT. SO IF YOU HAVE ON HERE AS WELL, WE HAVE A LOT OF BASED TECHNOLOGIES THAT IS AIMED AT LOOKING AT FALLS WHETHER PARKINSON PATIENT OR STROKE PATIENTS. I CAN TELL RECENTLY IN THE LAST FOUR OR FIVE MONTHS THAT SHOWS THAT IN ADDITION TO SHORTER STRIDE, WALKING SPEEDS WE CAN MEASURE IN CLINIC WE CAN DO œSOONERS DERIVE MEASUREMENTS. WE CAN ALSO LOOK AT ACTIVITY RECOGNITION SO WHEN IS SOMEBODY DOING EXERCISE, SITTING, WHEN ARE THEY NOT, PERHAPS THAT WILL COME UP LATER AS WELL. THIS IS REALLY IMPORTANT TO TRY TO IDENTIFY ARE PATIENTS DOING THE HOME EXERCISE WE WANT AND MORE IMPORTANTLY ARE THEY DOING THEM CORRECTLY. PATIENTS IN PARTICULAR LOW BACK PAIN IS AN EXAMPLE, WORK SHOWS THEY HAVE A REALLY WORK SENSE OFFER KIN AESTHETIC AWARENESS, THEY HAVE TROUBLE FEELING THE MOTIONS SO USING THE GAIN TECHNOLOGY TO TELL YOU HOW MUCH YOUR BACK IS MOVING TO TRACK THE NUMER OF REPS YOU ARE DOING AND HOW CORRECT AND TO ADJUST TASK DIFFICULTY IS THOUGHT TO HELP IMPROVE EXERCISE ADHERENCE, IMPROVE MOTIVATION AND IMPROVE OUTCOMES. THAT LEADS TO BIOFEEDBACK MOBILITY TRAINING USED WITH A VARIETY OF TECHNOLOGIES TO EXTEND REHAB SETTING OUT OF CLINIC, OUT OF A PLACE PEOPLE ARE PROBABLY HAVING THAT WHITE COAT SYNDROME, MAYBE NOT PERFORMING MOVING IN WAYS THEY DO WHEN THEY ARE MALLLY AT HOME AND WHEN THEY START TO SEE WHAT'S HAPPENING AS THEY MOVE AT HOME PRIMARILY USING THIS THUS FAR THOUGH THERE ARE SOME OTHER TECHNOLOGIES OUT THERE. BUT CERTAINLY WE ARE SEEING THAT ACCEPTSORS ARE BETTER ABLE TO ADDRESS ISSUES OF ASYMMETRY MANY PEOPLE WITH STROKE THAN NOT. WE HAVE SEEN IMU FOR FEEDBACK ON AT THE KNEE FOR MEDIAL OA AND HELPING PEOPLE AS PRECURSOR TO OSTEOARTHRITIS AND KNEE REPLACEMENT SO GOOD EVIDENCE WE CAN USE THESE TOOLS IN THOSE KINDS OF WAYS. GOING FORWARD SOME OF THE THINGS ON THIS LIST WE TALKED ABOUT, THERE'S ANOTHER TALK ON BIOMARKERS LATER BUT I WANT TO HIGHLIGHT A COUPLE OF THINGS THAT ARE REALLY IMPORTANT. ONE IS THE IDEA OF MOTOR RESTITUTION VERSUS COMPENSATION, I.E. AM I RECOVERING TO A EPRE-PATHOLOGICAL STATE OF MOVEMENT? GOING BACK TO BASELINE? IN CLINIC NEW POST PATHOLOGY COMPENSATION BASED MOVEMENT STRATEGY, WITH CHRONIC PAIN PATIENTS WE IDENTIFIED SEVERAL TIMES YESTERDAY WE DON'T SEE THESE PATIENTS UNTIL WELL INVOLVED MANY PAIN EPISODES RYING TO TEASE THIS INFORMATION OUT. CAN BE QUITE CHALLENGING. HAVING A BETTER UNDERSTANDING WHAT SORTS OF MOVEMENT PATTERNS ARE ASSOCIATED WITH PAIN RELATED BEHAVIORS MAY HELP UNDERSTAND WHETHER PATIENTS ARE TRENDING IN THE RIGHT DIRECTION. ARE THEY ACTUALLY CHANGING THE PATTERN IN A WAY WE WANT OR REINFORCING MOVEMENT PATTERN. I TOUCHED ON TELEREHABILITATION WITH GAMING AND CERTAINLY THE ABILITY TO EXTEND CLINIC TO THE WORLD IS VERY HELPFUL. EMG BASED SENSORS GIVE AN IDEA OF MOTOR CONTROL IS HELPFUL AND I WANT TO HIGHLIGHT THE HYBRID SENSORS SO NOW COMBINING SENSORS WITH INERTIAL MEASUREMENT UNITS TO GIVE SENSE OF QUALITY NOT JUST QUANTITY OF MOVEMENT SO ARE PATIENTS MOVING THE WAY WE EXPECT THEM TO MOVE. THE LAST THING I WANT TO MAKE SURE I HIGHLIGHT BECAUSE IT'S SPEAKS DIRECTLY TO THIS TALK YESTERDAY IS THE IDEA OF STRETCHING FABRIC AND GARNET BASED TECHNOLOGIES WITH PLACEMENT AND THINGS LIKE THAT. THERE'S EXAMPLES THINGS TO MEASURE, STUFF LIKE THAT AND KNOWING THAT I THOUGHT OF IMMEDIATELY TALKING YESTERDAY SMART SKIN BASED SENSORS THAT COMBINE EMS AND EEG SIGNALS, THERE'S ACTUALLY A GROUP IN TEL AVIV THAT STARTED TO UNITED STATES THESE TO TRACK SLEEP PROPERTIES, NOT JUST CHRONIC PAIN PATIENTS BUT IN GENERAL TO ATTACK ISSUES YOU WERE TALKING ABOUT WITH WHY IT'S HARD TO DO THESE STUDIES IN PATIENTS. I WILL FINISH WITH THE IDEA WE ARE ON THE PATH MOVING TO THIS COMPLETE INTEGRATION NOT JUST GIVING INFORMATION TO THE PERSON OR MEDICAL STAFF POST DOC OFFLINE BUT USE MACHINE LEARNING TO INTELLIGENTLY MANAGE REHABILITATION GOING FORWARD AND POTENTIALLY SOME AT SECRETARIES TRIGGERING RESPONSES SO SOMEBODY FALLS TRIGGERING AMBULANCE CALL OR IN A HEIGHTENED PAIN STATE TO TRIGGER MEDICAL FOLLOW-UP TO HELP MANAGE PAIN IN A MORE INCLUSIVE WAY. I'LL LEAVE YOU WITH THIS NOTION THERE ARE SOME CLEAR ISSUES TO THINK ABOUT GOING FORWARD. THE METRIC PROPERTIES OF SENSORS IS HUGE, ACCURACY RELIABILITY VALIDITY, ARE WE MEASURING WHAT WE THINK AND CONSISTENTLY IN PARTICULAR WHEN WE LOOK AT SMALL SUBTLE MOVEMENT PATTERNS. DATA SAFETY AND PRIVACY CONCERNS HIGHLIGHTED YESTERDAY I CAN'T SAY ENOUGH WE NEED TO THINK BIG AND LONG ABOUT WHAT ARE THE IMPLICATION OF SOME OF THIS TRACKING THAT WE ARE DOING. AND THEN SORT OF I FOCUS ON IS DEFINING WHAT ARE THE KEY OUTCOME MEASURES, WHAT IS CLINICALLY RELEVANT AND WHAT MATTERS WORK TO MAKE IMPACT ON PATIENT'S LIFE. SO APOLOGIES FOR BEING SLIGHTLY OVER. THANK YOU. [APPLAUSE] >> NEXT ASSISTANT PROFESSOR OF SPALDING NEUROIMAGING LAB AT HARVARD MEDICAL SCHOOL WILL BE DISCUSSING MOLECULAR IMAGING OF CENTRAL PAIN PROCESSES. DR. LINNMAN IS PSYCHOLOGY TRAINED IN POSITRON EMISSION TOMOGRAPHY AND MAGNETIC RESONANCE IMAGING WITH 15 YEARS EXPERIENCE IN MULTI-MODAL PAIN AND AFFECT. HE USED PET WITH MULTIPLE TRACERS TO DEFINE MONOANALGESIC AND DETERMINIC AND INFLAMMATORY ASPECTS OF CLINICAL PAIN IN CLINICAL ANXIETY. HE HAS FURTHER USED FMRI AND PET FMRI TO STUDY PAVULONIAN CONDITIONING MECHANISMS FOR DEFINING EMOTIONAL CIRCUITS IN PSYCHIATRIC DISEASE STATES. WELCOME. LOOK FORWARD TO YOUR PRESENTATION. >> THANK YOU. Q. I WAS GOING TO PUT UP THE IASP DEFINITION OF PAIN BUT THOUGHT IT WAS A STRONGER STATEMENT, NOT AFRAID OF DEATH BUT I WANT TO LIVE. IT'S PAIN THAT I CAN'T STAND. THIS IS -- WHO SUFFERED A LIFE OF CHRONIC -- AS A CHILD, PARTIALLY PARALYZED AT 6 YEARS OLD THEN IN 8 SHE WAS IN A HORRIBLE ACCIDENT, THAT CRUSHED HER PELVIS SPINAL CORD AND HAD A METAL ROD WE PUSHED THROUGH HER PELVIS AND ALMOST DIED AND DEVELOPED MULTIPLE CHRONIC PAIN SYNDROMES. DESPITE THIS SHE STILL HAS THAT ALMOST IMPAIRED LOOK, THIS IS ANY SITUATION, LOOK AT ME AND UNDERSTAND ME. SO I THINK WE REALLY NEED TO FOCUS ON PATIENT EXPERIENCE AND AS A PSYCHOLOGIST I COULDN'T AGREE MORE WITH THE PREVIOUS SPEAKERS ON THE EMOTIONAL IMPACT OF PAIN AND HOW MUCH THAT MODULATES YOUR PAIN BEHAVIOR. OF COURSE, I WANT TO START AS PAR FROM THE BRAIN AS POSSIBLE. SO WE HAVE BEEN LOOKING AT WAYS OF MEASURING CHRONIC LOW BRAID INFORMATION THIS IS A 42-YEAR-OLD MALE NURSE, HE SUFFERED A SLIGHT SACRAL INJURY. HE REPORTED BARELY ANY PAIN ON 0 TO 100 SCALE, 10 TO 15 AT REST BUT COULDN'T PUT ANY WEIGHT ON HIS FOOT. WE INVESTIGATED HIM USING PET CT WITH 11 DEPRINOL A MONOAMEAN OX DAYS B INHIBITOR. AND WE RACED PATIENTS RELATIVELY ACUTELY, COUPLE OF DAYS AFTER INJURY, FOUR WEEKS AND SIX MONTHS AFTER INJURY. HERE YOU SEE HIS OWN PAIN REPORTS, SO THREE LITTLE SPOTS WHICH WERE PARTICULARLY PAINFUL AND THE NICE THING ABOUT SPRAIN ANKLES, THEY RECOVER QUICKLY IN THE MAJORITY OF CASES AND WE HAVE CONTRALATERAL FOOT WITHIN SUBJECT CONTROL. HERE IS PET SCAN. FOUR WEEKS LATER STILL THERE SLIGHTLY REDUCED AND NOW ABLE TO PUT SOME WEIGHT ON HIS FOOT. SIX MONTHS OUTS THERE'S ABNORMAL UPTAKE. HE'S BACK PLAYING SOCCER AND HIS OTHER FOOT HE ACTUALLY HAD A SLIGHT SPRAIN ON HIS OTHER FOOT SO FULLY FUNCTIONAL THOUGH REPORTS SOME STIFFNESS IN THE MORNING. WE STILL SEE SOME TYPE OF PATHOLOGICAL UPTAKE SIX MONTHS LATER. HERE IS ANOTHER SUBJECT FIVE DAYS AFTER INJURY. HE FELL OFF A LADDER TWO AND GOT PINCHED BEHIND THE LADDER, FELL INTO A PIT, HE WAS UNABLE TO PUT ANY WEIGHT ON HIS FOOT, PAIN RATINGS THROUGH THE ROOF IF YOU WERE TO PALPATE HIM OBVIOUSLY. HE'S A PROFESSIONAL TANSER SO HE SAYS I'LL JUST HAVE TO DANCE ON MY LEFT FOOT. SO 40 DAYS LATER THE SWELLING HAS GONE DOWN A LOT, HE'S DANCING ON HIS LEFT FOOT, AND THE PET IMAGE IS ACUTELY MASSIVE INPROGRAMTORY RESPONSE. 40 DAYS LATER IT IS REDUCED BUT STILL QUITE LARGE. THEN FOUR MONTHS LATER IT'S ALMOST RESOLVED, YOU CAN SEE THE BEGINNING OF WHAT I THINK OF AS A OVERUSE INJURY, APPEARING IN HIS OTHER FOOT PROBABLY FROM DANCING ON HIS LEFT FOOT. SO OVER TIME LOOKING AT GROUP LEVEL, THIS IS THE RATIO BETWEEN THE UPTAKE IN INJURED FOOT AND CONTRALATERAL CORRESPONDING LIGAMENT. AND ACUTELY WE HAVE A BINDING THAT IS TEN TIMES AS HIGH. AS THE CONTRALATERAL FOOT. RESOLUTION WOULD BE RATIO GOING DOWN TO ONE. BUT EVEN SIX MONTHS LATER WE STILL HAVE UPTAKE THAT IS TWICE AS HIGH IN THE INJURED FOOT. CONTRALATERAL. THERE'S NO REAL CORRELATION BETWEEN THE UPTAKE AND NDVS PAIN RATINGS. THAT'S IN PART BECAUSE OF THE NON-VALIDITY OF VAS BUT ALSO DO WE ASK THEM AT REST OR AS SANDING ON HAIR FOOT, OR DO WE ATTEMPT TO FLEX THE ANKLE AND DETERMINE INJURY EXTENT THAT WAY. THERE WAS A RELATIONSHIP BETWEEN INITIAL UPTAKE AND SUBSEQUENT VISITS. I THINK THE MOST TELLING THING IS THIS CLEAR SPATIAL CORRELATION, SEE IF THIS WORKS. NOPE. THE SELF-REPORT AND WHERE WE SEE THE UPTAKE IN THE PATIENT. SO WE THINK THIS IS A GOOD MARKER OF LOW GRADE PERIPHERAL INFLAMMATION. WE DECIDED TO STUDY WHIPLASH PATIENTS WHICH IS A COMPLEX CONDITION TO SAY THE LEAST. THE MAJORITY OF PATIENTS WE COVER 50 TO 90% BUT -- THERE'S HARDLY ANY PATHOLOGY VISIBLE ON CT OR MRI. AND IF THERE ARE CHANGES IN THE DEEP NECK MUSCLE THEY ARE QUITE COMMON OVER 30 SO IT'S HARD TO ATTRIBUTE ANY PATHOLOGICAL CHANGES TO ACTUAL INJURY. THE INJURY MECHANISM IS THOUGHT TO BE CONTRARY TO THE NAME, IT'S NOT THE OVEREXTENSIONS OF FLEXION BUT RATHER IF YOU ARE IN YOUR CAR AND YOU ARE TAILGATED YOUR BODY IS THRUST FORWARD AND THERE'S A SHARING MOTION BECAUSE YOUR HEAD IS INERT SO ABOUT 75 MILLISECONDS INTO IT YOU HAVE S SHAPE OF THE SPINE THAT'S THOUGHT TO BE PATHOLOGICAL MECHANISM OF THE INJURY. HERE ARE PATIENTS, PET CT SCAN. SO THERE IS NORMAL UPTAKE IN SPIT GLANDS BUT YOU SEE A SPOT RIGHT THERE. WHICH IS ABNORMAL. LOOKING AT THE CT, IT'S QUITE CLEAR IN THE DEEP MUSCLE THERE'S ELEVATED UPTAKE. LOOKING AT 22 PATIENTS WE SEE THIS SEEMS TO BE A SPOT WHERE THERE IS CHRONIC LOW GRADE INFLAMMATION IN PATIENTS, THIS IS IN RED YOU SEE PATIENTS AND THIS IS THE UPTAKE CURVE OVER TIME OF THE PET TRACER. IN BLUE YOU SEE SEVEN HEALTHY CONTROLS SO IT'S MUCH LOWER UPTAKE IN PATIENTS. WE SPENT TIME LOOKING AT ARE WE LOOKING AT MONOAMEAN OX DAYS WHICH IS NOT EXPRESSED IN PERIPHERY OR INFLAMMATORY STATES, WE DON'T THINK THAT'S WHAT WE ARE SEEING BUT THE TRACER IS BINDING TO ANOTHER PROTEIN BUT NOT SPECIFIC TO MAOB OR MAOA FOR THAT MATTER SO NOT SURE WHAT WE ARE SEEING BUT THERE'S SOMETHING THERE. ANOTHER APPROACH HAS BEEN TO LOOK AT PERIPHERAL INFLAMMATION AND TREATMENT. WE ARE USING A TRACER CALLED GOB WHICH BIND TOP THE NEUROENDOCRINE RECEPTOR SUBSTANCE P BINDING SITE. AND WE STUDIED PATIENTS WITH CHRONIC -- THREE MONTHS LATE AT THESE THREE MONTHS OF CHRONIC TENNIS ELBOW INJURY. AND WE PLACED THEM LIKE THIS MANY THE SCANNER TO CAPTURE THEIR ARMS AND THEIR BRAIN ALSO SO WE'LL GET INTO. AND IN NINE OF TEN PATIENTS WE SEE ELEVATED UPTAKE IN THE AFFECTED LIMB. IS THIS RESPONSIVE TO TREATMENT? WE TREATED THEM WITH DAILY EXERSIZE, BASICALLY A WATER BOTTLE THAT YOU LIFT THEN EXTEND DOWN AND CONCENTRIC LIFT AND LOWER IT DOWN YOURSELF. EVERY WEEK WE ADD SOME WATER TO THE BOTTLE SO INCREASING LOAD. OVER THREE MONTHS. AND IN THE LARGE GROUP WE HAD A GOOD SUCCESS 23 POINTS ON 0 TO 100 SCALE BOTH AS LOADING THEIR ARMS SO WHEN THEY WERE -- WHEN WE WERE PROVOKING PAIN. BUT THE RECEPTOR EXPRESSION IN INJURED ARM DID NOT CHANGE ALL THAT MUCH. SO IF WE PLOT CORRELATION BETWEEN REDUCTION IN BAS PAIN AND THE REDUCTION IN NEUROKININ 1 RECEPTION IN THE PERIPHERY, THERE MAYBE CORRELATION THERE JUST NOT A SIGNIFICANT RELATIONSHIP SO ONE OF THE CONCLUSIONS IS AS WE DOES CUSSED BEFORE, THIS PERIPHERAL INJURY IS MAYBE NOT RELATED TO PAIN EXPERIENCE BUT THERE'S CERTAINLY SOMETHING THERE. I THINK MEASURING THAT SOMETHING ADDS A LOT OF VALUE. ET CETERA SPECIALLY TO PATIENTS. THERE'S A LOT OF WHIPLASH PATIENTS HAVE GONE THROUGH YEARS OF LITIGATION AND THEY ARE NOT BELIEVED BY THEIR PHYSICIANS THEN WE SHOW THEM THIS PET IMAGE, THERE'S SOMETHING GOING ON WE CAN'T TREAT IT BUT YOU ARE RIGHT, THERE IS A -- PROBABLY A PERIPHERAL DRIVER. I THINK OF THIS AS THAT KID, IN THE SEAT BEHIND YOU ON THE AIRPLANE KICKING YOUR SEAT. MINDFULNESS IS GREAT BUT YOU WANT THAT KID TO STOP SOMEHOW. MINDFULNESS GETS YOU FAR BUT NOT ALL THE WAY. SO I THINK WE SHOULD FOCUS, WE SHOULDN'T DISREGARDED THE PERIPHERAL INJURY DRIVING THE PAIN STATES. I THINK THERE ARE MECHANISMS OF CENTRAL SENSITIZATION, OR DA TAS STRAY ADVERTISING. I FOR ONE CANNOT STOP WAITING FOR THAT KID TO START KICKING AGAIN WHICH IS ANTICIPATION OF CHRONIC PAIN REAPPEARING BUT I THINK BECAUSE WE ARE NOT OBSERVING PERIPHERAL DRIVER OF INJURY, DOESN'T MEAN IT'S NOT THERE SO WE MAY BE ABLE TO MEASURE THAT. SWITCH GEARS, THIS IS WORK CHAMPIONED BY (INAUDIBLE) USING PBR 28 WHICH BINDS TO ACTED MICROGLIA, SO MICROGLIA ARE STAR LIKE, HENCE THEIR NAME AND SENSING NEURONS CHECKING IN ON THEM, DETERMINING PERIPHERAL OR CENTRAL PATHOLOGY. MIGRATE TOWARD A INJURY, WHEN THEY DO THAT THEY START EXPRESSING SURFACE PROTEIN, THERE ARE ACTIVE MICROGLIA. WE ARE STUDYING PATIENTS WITH NEUROPA THICK PAIN AT LEVEL OR BELOW LEVEL. MOST OF THEM HAVE OTHER TYPES OF PAIN GOING ON EITHER FROM WHEELING AROUND OR SITTING OR JUST BEING IMMOBIL AND BEING IN A CHAIR, LOWER BACK PAIN IS QUITE COMMON, IF THEY ARE ABLE TO SENSE LOW BACK. AND ON A GROUP LEVEL, WE SEE THAT THE HIPPOCAMPUS APPEARS INFLAMED IN THE PATIENTS. WE REPLICATED THIS IN AN ANIMAL MODEL AND BOTH WITH PET IMAGING WHICH IS SO 55 DAYS POST CONTUSION INJURY, THERE IS ELEVATED HIPPOCAMPAL MICROGLIAL ACTIVITY IN ANIMALS ALSO. LOOKING AT HISTOLOGY THERE IS THROUGHOUT THE NEUROAXIS FROM PAG FROM THE SITE OF LESION ALL THE WAY UP TO THE SOMATOSENSORY CORTEX, THERE IS A LOT OF ACTIVATED MICROGLIA. WE HAVE NO CLEAR RELATION IN THIS DATA YET TO NEUROPATHIC PAIN PARTLY BECAUSE WE DON'T HAVE ENOUGH PATIENTS, WE ARE UP TO 15 AND RATHER BE ABLE TO SEPARATE GROUP OF 30 PATIENTS OR SO WITH OR WITHOUT NEUROPATHIC PAIN. WE DO HOWEVER HAVE FUNCTIONAL IMAGING, WE ALREADY TALKED FUNCTIONAL CONNECTIVITY, I'M USING A MEASURE CALLED AMPLITUDE OF LOW FREQUENCY FLUCTUATIONINGS SO IT'S A RESTING STATE METRIC BUT NOT ACTIVITY BETWEEN REGIONS, RATHER IT'S THE POWER OF FLUCTUATION IN BOLD SIGNAL, REGION BY REGION. IF WE RELATE THIS TO PAIN RATINGS, WHICH RANGE FROM 0 TO 8 ON VAS SCALE, WE SEE THAT THE PERIDUCTILE GRADE, THE PRIMARY SOMATOSENSORY CORTEX IN THE LOWER TRUNK REPRESENTATION REGION, PREFRONTAL CORTEX ARE CORRELATED TO BAS RATINGS IN THESE PATIENTS. WE HAVEN'T LOOKED AT CATATRAPHIZING YET, WE HAVE COLLECTED THAT DATA -- WE HAVEN'T COLLECTED THAT DATA BUT CERTAINLY ON THE TO DO LIST TO NETWORK IN SILICA ACTIVITY, IS REPLICATING ALSO IN THIS PATIENT POPULATION. NOW WE ARE USING EXERCISE AS A TREATMENT, IT'S A BROAD TREATMENT. THIS IS A PATIENT ROWING FOR THE FIRST TIME SINCE INJURY. SO WE PUT ELECTRODES ON HIS LEGS. FES STIMULATION. QUITE LIKES IT THIS IS HIS FIRST TIME MOVING HIS LEGS SINCE INJURY. GOOD FEELING FOR A LOT OF PATIENTS TO BE ABLE TO DO THAT. THIS IS A DIFFERENT SUBJECT BUT CASE WITH C 7 COMPLETE INJURY, WE DID FIRST PET MR SEVEN MONTHS POST INJURY, HE UNDERWENT 12 WEEKS OF ROWING, HAD TO WALK 26% INCREASE, MAXIMAL OXYGEN UPTAKE SO PUSHED HIMSELF AND HAD A HUGE INCREASE. HIS PAIN RATINGS WENT FROM 19.5 TO ZERO ON THE MCGILL PAIN RATING SCALE. THIS IS ON A GOOD DAY AT THE SECOND -- NOT PAIN FREE BUT WE CAPTURED HIM ON A GOOD DAY AT SECOND PET MR. LOOKING AT THE STRUCTURAL SCANS PRE-POST INTERVENTION WE SEE A CHANGE IN HIPPOCAMPAL VOLUME, NOT SURE IF WE CAN CALL THAT NEUROGENESIS, 12 WEEKS SEEMS OVER TOP, BUT IT WAS SURPRISING TO SEE SIGNIFICANT CHANGES IN STRUCTURE THERE. LOOKING AT PBR 28 WE SEE 5% REDUCTION AGAIN IN THE HIPPOCAMPUS. CURRENTLY RYING TO REPLICATE IN MUCH LARGER STUDY, STUDYING ABOUT 35 PATIENTS IN RANDOMIZE CONTROL STUDY SO RANDOMIZING TO TREATMENT AS USUAL FOR THIS FES INTERVENTION. AND TRACKING WITH GLIAL IMAGING AND OPIOID PET IMAGING SO THE OUTCOME MEASURES, CAN WE SEE REDUCED NEURAL INFLAMMATION, CAN WE SEE INCREASE IN OPIOID RECEPTOR BINDING POTENTIAL SO ARE WE ENABLING ENDOGENOUS OPIOID SYSTEM TO BE MORE RESPONSIVE. WE ARE DOING QST AND MORE COMPREHENSIVE PAIN ASSESSMENTS IN PATIENTS. WE ARE ALSO LOOKING AT EXOSKELETON AS TREATMENT. THIS IS STUDY WITH LESLIE MOORE'S AT CRAIG HOSPITAL AND SHE'S NOW AT UNIVERSITY OF MINNESOTA. PATIENTS ARE WALKING IN EXO SKELETON SIX MONTHS, STUDY IS ON BONE HEALTH BUT MANAGED TO GET MRI IN THERE. BASELINE AND P TREATMENT AND PRELIMINARILY WE SEE TREATMENT INTERVENTION CHANGES FUNCTIONAL ACTIVITY PERIDUCTILE GRADE AND LEFT AND RIGHT SIDE. IN TERMS OF PAIN RATINGS, THERE'S NO CLEAR REDUCTION IN THE SMALL SAMPLE COMPLETING STUDY, I THINK HALF A YEAR FROM NOW WE'LL HAVE A FULL SAMPLE TO TELL YOU MORE IF IT'S REALLY BENEFICIAL BUT YOU HAVE TO REMEMBER PATIENTS HAVE MULTIPLE PAIN ISSUES SO THE INTERVENTION IS MORE WALKING THAN TARGETING THE PAIN PER SE. TO CONCLUDE WE ARE OBSERVING ELEVATED GLIAL RESPONSE IN HIPPOCAMPUS AND CHRONIC SPINAL CORD INJURY. WE THINK THIS MIGHT BE TREATABLE WITH GOOD BOUGHT OF EXERSIZE SO ROWING IS GREAT BECAUSE ENGAGES ENOUGH MUSCLES TO STRESS YOUR HEART SO YOU HAVE ACTUAL AEROBIC RESPONSE, WHEREAS UPPER BODY PSYCHING FOR EXAMPLE DOES NOT ENGAGE ENOUGH MUSCLES TO HAVE THAT STRONG ANTI-INFLAMMATORY BENEFIT. NEUROPATHIC PAIN LEVELS WERE CORRELATED TO PAG PREFRONTAL AND S 1 SIGNAL POWER. WE WILL LOOK DEEPER TO SEE HOW THAT CHANGES WITH TREATMENT. THE CONCLUSION IS THESE INTERVENTIONS METRICS CAN INFORM WHAT IS GOING ON WITH PATIENTS. IT ADDS NEW LEVEL OF INSIGHT TO WHAT MIGHT BE GOING ON. WE WANT TO GET TO MECHANISMS SO CARDIO VASCULAR EXERCISE ANTI-INFLAMMATORY OR ARE YOU STRENGTHENING ENDOGENOUS OPIOID SYSTEM, ARE YOU GROWING ARE FEELING BETTER? THAT IS CERTAINLY A POSSIBILITY. THESE PATIENTS WILL BE ENGAGED IN COMMUNITY OF OTHER ROWERS DO SOMETHING DAILY, IT'S A ROUTINE SO THAT MIGHT BE THE REAL REAL BENEFIT. I THINK GOING FORWARD WHAT I WOULD LIKE TO DO IS TRACK NOCICEPTION FROM THE PERIPHERY FROM THE START PICTURE TO THE WHOLE BODY PET MR. SO CAN WE TRACK THE WHOLE PAIN PATHWAY FROM A PERIPHERAL LOW GRADE INFLAMMATION TO CENTRAL RESPONSE AND THEN ON TO HOW DOES THAT IMPACT BEHAVIOR. THIS WORK WAS DONE BY SUPPORT OF NIH. SOME OF THE PERIPHERAL IMAGING WAS SUPPORTED BY INSURANCE COMPANY. WORK ON PERIPHERAL -- CENTRAL GLIAL IMAGING IS SUPPORTED BY DOD. THE NEW STUDY WE ARE DOING EXERCISE INTERVENTION IS SUPPORTED BY NICHD. THAT IS ALL. THANK YOU. [APPLAUSE] >> THANK YOU VERY MUCH. THE FINAL PRESENTER FOR THIS PANEL IS DR. LUCA FASCHINI, CO-FOUNDER AND INNOVATION SCIENTIST FOR DATA HEALTH, DATA ANALYSTS AND REHAB DEVELOPMENT HE'S DRIVEN RESEARCH COLLABORATIONS RESULTING IN PUBLICATIONS IN THE FIELD OF MACHINE LEARNING, BEHAVIORAL ECONOMICS AMEND MEDICAL INFORMATICS. PREVIOUSLY, DR. FASCHINI HELD RESEARCH POSITIONS IN INDUSTRY AND ACADEMIC INSTITUTIONS, INCLUDING GOOGLE, ZURICK AND UC SAN A BARBARA. HE CO-AUTHORED PAPERS AND PATENTS ON EFFICIENT ALGORITHMS FOR PARTITIONING AND DETECTING ANOMALIES IN MASSIVE NETWORKS. THANK YOU VERY MUCH FOR BEING HERE TODAY. >> THANK YOU, EVERYONE, THANKS FOR INVITING ME. MY PERSPECTIVE WILL BE DIFFERENT TALKING MOSTLY ABOUT THE DATA PART OF THINGS AND VERY FAR AWAY FROM MECHANISM, BACKGROUND IS IN COMPUTER SCIENCE, I HAVE NO CLINICAL TRAINING IN PAIN. SO BEAR WITH ME IF I SAY SOMETHING THAT DOESN'T RESONATE FROM A CLINICAL PERSPECTIVE, HAPPY TO CHAT AFTER FOR CLARIFICATION. SO THE PRESENTATION IS IN THREE PARTS. FIRST TALK ABOUT ABOUT THE PROMISE OF PERSON GENERATED HEALTH DATA AS NEW DATA THAT CAN INFORM MEASURES OF MULTIPLE THINGS INCLUDING PAIN, WE LOOK AT SPECIFIC STUDIES THAT USES PERSON GENERATED HEALTH DATA TO INFORM MEASURE OF PAIN SPECIFICALLY AND THEN A CASE STUDY BUILT ON THAT DATA SET. PERSON GENERATED HEALTH DATA PGHD IS ACRONYM I HAVE LEARNED TO CALL THEM SO IT MEANS ACRONYM RETROFITTED TO DIFFERENT MEANING THAN INITIALLY WAS. HE USED TO BE CALLED PATIENT GENERATED HEALTH DATA BY DEFINITION OF ONC. THE WHOLE SET OF DATA THAT CAN -- THAT ARE COLLECTED AND MEDIATED BY A PATIENT AND CAREGIVER TRACKING HEALTH. YOU CAN HAVE A FUTURE UM TAKE WHAT THIS DATA IS LIKE, FOR THAT I REFER TO THIS INFO GRAPHIC FROM SCIENCE NATURE MEDICINE A COUPLE OF YEARS AGO, SMART SENSOR AND IMPLANTABLE WEARABLE OF COURSE YOU ARE SMART HOME AND AUTOMOBILE WILL COME AND MEASURE HEALTH BUT ONE FUNDAMENTAL PIECE OF PGHD IS PATIENT REPORTED OUTCOME. THE VOICE OF THE PATIENT. WE WILL TALK ABOUT THAT IN THIS PRESENTATION. WE BELIEVE REALLY DATA COLLECTED SPECIFICALLY PGHD COLLECTED OUTSIDE THE CLINIC WALLS CAN INFORM WHAT'S GOING ON WITH LIFE OF A PATIENT, OF A PARTICIPANT IN RESEARCH STUDY, OF A USER, OF APPLICATION IN BETWEEN THOSE SPORADIC AND BIASED TOUCH POINTS WE HAVE WITH THE HEALTHCARE SYSTEM. I HOPE THEY ARE SPORADIC WHEN IT COMES TO HEALTH PRACTICE AND STILL SPORADIC WHEN IT COMES TO HEALTH RESEARCH. THE TOP IS LIKE A ILLUSTRATION HOW RARE THE TOUCH POINTS ARE AND BOTTOM IS WHAT DATA FILLS IN AND TELL US. THERE'S MANY WAYS TO COLLECT THE DATA, THERE'S SOME OF THOSE ARE BETTER THAN OTHER. IT'S REALLY EASY TO TO IT THE WRONG WAY IF YOU COME FROM TECHNOLOGY, WHICH IS WITHOUT PATIENT PERMISSION. WE HAVE CREATED THIS PLATFORM, THIS APP THAT IS NOW IN THE HANDS OF 3.5 MILLION USERS IN THE UNITED STATES AND LARGEST RESEARCH COHORT IN THE UNITED STATES. IN WHICH PARTICIPANTS ARE ENGAGED WITH THEIR WELLNESS BY CONNECTING ANY WEARABLE DEVICE AND APPS OUT THERE AND THEY RECEIVE POINTS FOR THAT CONNECTION. BUT DURING THE INTERACTION WITH THEIR WELLNESS THEY GET OFFERED RESEARCH OPPORTUNITIES. SO AT THAT POINT JOIN RESEARCH STUDIES LIKE ONE I WILL TALK ABOUT IN A MINUTE ON CHRONIC PAIN. AND THEN IT BECOMES A RESEARCH STUDY SO INFORMED CONSENT IRB APPROVAL, EVERY DATA POINT IS CONSENTED FOR A SPECIFIC USE OF THE STUDY SO IF I SAY I'M COLLECTING YOUR DATA TO STUDY PAIN BUT LATER ON I WANT THE SAME DATA TO UNDERSTAND FLU, WE WILL RE-CONSENTTOR DIFFERENT USE TO THE SAME PERSON. WHAT THIS DATA CAN DO, THIS IS NOT A PRESENTATION WE TALK ABOUT THAT, SO JUST GOING TO THROW OUT A FEW IDEAS THERE. . IT CAN REALLY HELP MEASURE DIFFERENT THINGS. , THINGS MEASURED IN REAL WORLD SETTING BEFORE, FOR INSTANCE HERE ARE TWO EXAMPLES COMPARING A TYPE 2 DIABETES PATIENT WITH TYPE 2 DIABETES COMPARED WITH MATCH CONTROL, YOU CAN SEE THAT USUALLY YOU COMPARE THEM IN CO-MORBIDITY BURDEN, AGE DEMOGRAPHICS, OTHER MEASURE OF HEALTH, A 1C WILL BE ONE OF THOSE. BUT HEY, IF YOU HAVE JUST A FIT BIT LIKE THE LOWEST GRADE WEARABLE COMMERCIAL DEVICE YOU HAVE OUT THERE YOU CAN GET THE SLEEP DURATION, PROBABLY NOT STAGING BOATABLE TIME SLEEPING AND YOU CAN SEE PEOPLE WITH TYPE 2 SLEEP LESS, THEY SLEEP LESS REGULARLY SLEEP REGULARITY INDEX, YOU CAN MEASURE RESTING HEART RATE AND COMPARE DURING COHORTS, THE SAME YOU CAN DO PATIENT WITH MULTIPLE SCLEROSIS, THAT'S THE RIGHT HAND SIDE OF THE SLIDES AND MATCH CONTROL IN THAT PARTICULAR CASE THE VARIABLE STANDS OUT SIGNIFICANTLY DIFFERENT WEAN THE TWO COHORTS IS TIME TO FALL ASLEEP WHICH IS NOT UNEXPECTED BUT IS NICE TO BE ABLE TO MEASURE THAT IN THE WILD. JUST ANOTHER EXAMPLE BEFORE WE GO INTO PAIN SPECIFICALLY, ONE OF THE BIG POWER IN MY OPINION OF PGHD IS THAT IT'S EASY TO CONTINUOUSLY COLLECT IT. SO AT THE POINT YOU CAN CREATE A HISTORY OF MEASUREMENT, AND WHEN YOU HAVE CONTINUOUS DATA YOU CAN COMPETE DERIVATIVES LOOK AT CHANGES. YOU CAN USE FOR INSTANCE IN THIS PARTICULAR CASE STEP COUNTS AT THE DAILY LEVEL AND RESTING RATE AT DAILY LEVEL TO STUDY THE EVOLUTION OF FLU. ON A POPULATION LEVEL. FLU IS A VERY ACUTE EVENT. THAT GETS PEOPLE TO NOT WALK AS MUCH. AND THIS TELLS YOU THIS TELLSES YOU HOW MUCH IS MUCH. ALSO SIGNIFICANTLY CHANGING YOUR RESTING HEART RATE. AS YOU CAN SEE IN THE RIGHT HAND SIDE OF THE SLIDE. INCIDENTALLY A FEW WEEKS AGO, A PUBLICATION CAME OUT THAT USES SIMILAR DATA SETS AND USES A CHANGING RESTING HEART RATE TO ESTIMATE THE NUMBER OF PEOPLE THAT ARE ACTUALLY BEING UNDER FLU EVENT. THEREFORE CAN ESTIMATE THE PEAK OF FLU INFECTION AT THE CDC WOULD BE INTERESTED IN. NOW, SWITCHING GEARS, LET'S GO TO PAIN. ONE OF THE STUDIES -- RAN STUDY MOSTLY FOR SPONSOR, PHARMA COMPANY, ACADEMICS, PROVIDERS, COME AND RUN THE STUDY, AND RUN A STUDY SO WE COLLECT DATA, DESIGN STUDY. WE DO A LOT OF THAT, THAT'S OUR MAIN BUSINESS. WE ALSO SPONSOR STUDY OURSELVES. AND DISCOVER I IS ONE OF THOSE. DISCOVER IS DIGITAL SIGNALING IN CHRONIC PAIN IS ONE YEAR LONG TUESDAYNAL COHORT STUDY CONNECTED VIRTUALLY. SO FULLY VIRTUALLY IN THE UNITED STATES, WITH 58,000 -- SORRY 5800 INDIVIDUALS SELF-REPORT CHRONIC PAIN AND 4200 CONTROL MATCHED SLIGHTLY MATCH DEMOGRAPHICS. THAT IS A MAP OF THE UNITED STATES WITH YELLOWS AND GREEN POINTS WHERE PEOPLE WITH PAIN AND WITHOUT PAIN LIVE AND POINT OF THAT MAP IS THAT IT LOOKS LIKE A POPULATION MAP OF THE UNITED STATES. PRETTY SPREAD OUT, NOT JUST CALIFORNIA, SAN FRANCISCO WHERE WE ARE. AND HAS BEEN REALLY NICE TO BE ABLE TO SEE A DAY DIVERSITY OF DATA YOU CAN COLLECT. I WILL GO THROUG A FEW READ OUTS, THIS WAS PRESENTED LAST YEAR AT I SPORE IN MAY. SO FOR EVERYONE WE COLLECTED BASELINE INFORMATION AROUND DEMOGRAPHICS, QUALITY OF LIVING, ANXIETY DEPRESSION BUT CO-MORBIDITY BURDEN YOU CAN SEE MORE THAN 6% OF CHRONIC PAIN SUFFER IN OUR POPULATION DISCOVER SUFFER FROM MIGRAINES. THERE IS A HYPERLENS OF FIBROMYALGIA AND RHEUMATOID AREOLITIS AS WELL REPRESENTED THERE. THIS IS THE DISTRIBUTION ON THE HUMAN BODY WHERE PAIN MOSTLY COMES FROM, A LOT OF HEAD AND MEMBERS OF THE JURY, SHOULDER, AND MOSTLY THE PAIN HIGHEST PREVALENCE PAIN REPORTED IS LOWER BACK IN OUR POPULATION. HERE WHAT GETS INTERESTING, WHAT GETS MORE INTERESTING IS PART OF THE INFORMATION WE COLLECT IS AROUND TREATMENT AND TREATMENT PREFERENCES. SO A LOT OF PEOPLE REPORT TAKING OFF THE COUNTER MEDICATION, PRESCRIPTION BASED MEDICATIONS AND ALTERNATIVE THERAPIES, ON THE LEFT, PREVALENCE OF THOSE VERY INTERESTING TO SEE THE DIGITAL APPS ARE MORE THAN 40%, CLEARLY TELLING YOU THIS POPULATION IS NOT REPRESENTATIVE OF THE WHOLE CHRONIC PAIN POPULATION IN THE UNITED STATES, THESE ARE PEOPLE THAT ARE VERY ENGAGED WITH TECHNOLOGY. BUT THAT BECOMES MORE INTERESTING MEMBER YOU COMPARE WHAT PEOPLE ARE USING. WHAT PEOPLE THINK IS WORKING WHICH IS THE RIGHT HAND SIDE. SO SELF-REPORTED EFFECTIVENESS OF THIS SELECT PAIN STRATEGY YOU SEE THAT OPIOIDS ARE OUT THERE BOTH CT LOSES A LOT OF POWER, AND MASSAGE THERAPY IS UP THERE WITH OPIOIDS MANY THE SPECIFIC POPULATION WHICH IS I FIND IT INTERESTING ONLY TO BE ABLE TO COMPARE TO BE ABLE TO MEASURE& THIS. A GOOD MAJORITY OF THE PARTICIPANTS ALSO HAD CONNECTION PRE-EXISTING CONNECTION WITH COMMERCIAL WEARABLE DEVICES MOSTLY FIT BIT DATA. SO WE CAN MEASURE ACTIVITY IN IN SOMEWHAT OBJECTIVE WAY. YOU CAN SEE THERE ARE NUMBERS PER DAY, AND THE HOUR SPANS AND THE RESTING HEART RATE ARE LIKE CHANNELS THAT YOU ANALYZE THE MOST IF YOU HAVE A FIT BIT HEARTED RATE, THERE IS A BIG DIFFERENCE IN ACTIVITY PROFILES FOR PEOPLE WITH CHRONIC PAIN AND WITHOUT CHRONIC PAIN IF THEY DIFFER IN DEMOGRAPHIC IS SMALL, TWO YEARS OF AGE. I'M GOING TO TALK MORE ABOUT THE RELATIONSHIP BETWEEN PAIN AND ACTIVITY LATER ON. IN TWO WAYS. ONE IS AS DIRECT CORRELATION. SO CAN WE USE ACTIVITY AS MAYBE MEASURE TO PROXY, CONVERGENT VALIDITY CORRELATES WITH PAIN BUT ALSO I SHOW ACTIVITY DATA COULD BE USED TO CONTROL UNDERSTANDING OF PAIN. SO THE READ OUTS AGAIN THIS IS MOSTLY DATA THAT WAS READ OUT LAST YEAR AT AS FOR MAYBE TAKE AWAYS CHRONIC PAIN IN OUR COMORBID WITH A VARIETY OF HEALTH CONDITIONS OF THE RELIEVERS ARE COMMONLY USED BUT DEEMED NOT SO EFFECTIVE. OPIOIDS ARE BUT SO ARE OTHER TREATMENTS PROBABLY LESS ADDICTIVE. YOU CAN SEE SIGNIFICANT DIFFERENCE BETWEEN PEOPLE REPORTING CHRONIC PAIN AND MATCH CONTROL ON ACTIVITY SPECIFICALLY STEP SLEEP AND HEART RATE ONE MEASURE COMMERCIALLY AVAILABLE DEVICESES IN THE WILD, EVERY DAY LIFE CONDITION. A LITTLE MORE CASE STUDY IN DEPTH OF WHAT CAN YOU DO WITH THIS DATA. WE WILL GO INTO WHAT CAN WE DO WITH THIS DATA. ONE OF OUR BIG INTERESTING RUNNING THE STUDY IS ABILITY OF BRINGING IN RESEARCHERS THAT CAN ASK QUESTIONS ABOUT CHRONIC PAIN NOT EASILY ANSWEREDDED IN CLINIC BUT ARE MORE -- CAN FIND A BETTER ANSWER IN REAL WORLD LARGE DATA SETS LIKE ONE I'M PRESENTING HERE. THIS IS PRESENTED LAST YEAR, A FEW MONTHS AGO SOCIETY FOR -- IT'S LOOKING AT WHERE BASICALLY FINDING THE SAME FINDINGS THAT HAVE BEEN FOUND IN THE LITERATURE THAT AFRICAN AMERICAN EXPERIENCE HIGHER BURDEN OF PAIN WITH RESPECT TO NON-HISPANIC WHITES AND WE ARE ABLE TO SHOW THAT THAT HAPPENS ALSO WHEN YOU CONTROL FOR ACTIVITY DATA WHICH IS SOMETHING YOU CAN ONLY DO IF YOU HAVE A DATA SET THAT HAS BOTH. SO THE SPECIFIC STUDY HERE IS WE LOOK AT THIS TWO OUTCOME VARIABLES, ONE PAIN SEVERITY MEASURE WITH BPI AND THE OTHER ONE IS PAIN INTERFERENCE, AGAIN, A MEASURE FROM 0 TO 10 OF HOW PAIN IS INTERFERING WITH YOUR GENERAL ACTIVITY MOOD WALKING NORMAL WORK RELATIONSHIP. WE CONSIDER ONLY PEOPLE THAT HAVE ACTIVITY DATA FROM COMMERCIAL WEARABLE DEVICES AND THAT DATA IS DENSE MEANING NO MORE THAN SEVEN CONSECUTIVE DAYS WITH NO ACTIVITY SO THEY HAVE TO WEAR DEVICE TO MAKE ANY INFERENCE FROM THAT. THIS IS INCLUSION CRITERIA, THE POPULATION WE GOING TO ANALYZE IN THE END IS AROUND 2000 PEOPLE. THIS IS THE RACIAL DISTRIBUTION. YOU CAN SEE SELF-REPORTED BLACK AFRICAN AMERICAN ARE 4%, BLACK BIRACIALS ARE UP TO 6%, BY NO MEAN CLOSE TO NATIONAL PREVALENCE WHICH IS AROUND 12% FOR AFRICAN AMERICAN BUT OUR CLAIM IS BETTER THAN A LOT OF THE RICHER STUDIES WE HAVE IN TERMS OF REPRESENTATION OF DIVERSITY. IN FACT, IT ALLOWS US TO TO BE ABLE TO MAKE THIS COMPARISON ACROSS RACE ETHNICITIES THAT USUALLY ARE NOT AMENABLE TO BEING DONE DUE TO TOO LOW NUMBERS, SMALL POWER. COUPLE MORE SLIDES, MAIN FINDINGS HERE. FIRST OF ALL REGARDLESS OF RACE, THE OBVIOUS, REGARDLESS OF RACE, ACTIVITY DATA NEGATIVELY CORRELATES WITH SELF-REPORTED PAIN, THE MORE PAIN YOU FEEL LESS YOU WALK AND THE DATA IS REPORTED THERE. THAT IS NOT SURPRISING AT ALL. AND IT'S ALSO MOSTLY FOR US IT'S A REINFORCEMENT THAT THE DATA WE COLLECT HAS VALIDITY, IT TELLS YOU THE EXPECTED. NOW, REGARDING THE POINT I WAS MAKING ABOUT DIFFERENTS IN RACE, WE CAN SEE THAT EVEN WHEN CONTROLLING FOR ACTIVITY, AGE AND GENDER, BLACK AFRICAN AMERICANS REPORT 0.8 POINTS OF PAIN HIGHER THAN NON-WHITE AMERICANS SO THEY EXPERIENCE A BURDEN OF PAIN ABOVE AND BEYOND CO-VARIANTS SUCH AS DIFFERENT PHYSICAL ACTIVITY WE HAVE TO WALK MORE AND CONTROLLING FOR THAT. THAT'S ONE OF THE BEAUTIES OF THIS VERY HIE VARIETY DATA SETS ALLOWS POTENTIAL CONFOUNDERS YOU WOULDN'T MEASURE OTHERWISE IN THE WILD CONDITION. THE SAME WE SEE WITH PAIN INTERFERENCE THE EFFECT SIZE IS SMALLER IN TERMS OF DIFFERENCES BETWEEN RACES. 0.5 POINTS HIGHER EXPERIENCE PAIN INTERFERENCE WHEN CONTROLLING FOR EVERYTHING ELSE. WHAT'S INTERESTING HERE IS THAT NOW IF YOU LOOK AT CORRELATION BETWEEN PAIN INTERFERENCE AND PHYSICAL ACTIVITY, NUMBER OF STEPS SPECIFICALLY, THEN OF COURSE IT'S HIGH AND SIGNIFICANT BUT EFFECT SIZE IS TWICE AS MUCH ALMOST THREE TIMES IT WAS FROM STEPS AND PAIN PERCEPTION WHICH ALSO MAKES SENSE SO LIKE YOU -- THE PAIN INTERFERENCE IS MORE OF A MEASURE OF HOW PAIN IS IMPAIRING YOUR BEHAVIOR WHICH IS MUCH MORE CLOSE TO THE NUMBER OF STEPS YOU TAKE THAN THE PAIN SEVERITY ITSELF. SO THAT IS ALSO LIKE ADDITIONAL VALIDATION TO US OF THIS DATA MAKES SENSE, THIS DATA GOES IN THE RIGHT DIRECTION AS YOU EXPECT. SO LIMITATION OF COURSE THERE ARE MANY, THIS IS A STUDY IN THE REAL WORLD SO EVEN THOUGH YOU CAN CLAIM PGHD YOU CAN MEASURE MORE THINGS YOU CAN MEASURE BEFORE, THERE'S STILL A LOT OF CONFOUNDERS OUT THERE. I HAVE BEEN TALKING A LOT ABOUT PHYSICAL ACTIVITY BUT IN REALITY THE MEASURE OF USE IS STEP COUNTS, WHICH IS JUST A PROXY FOR THAT. THERE ARE MANY OTHER WAYS OF MEASURING AND WE ACTUALLY ARE WORKING ON THOSE. SO THOSE ARE THE MAIN LIMITATION. OF COURSE THE GROUP THAT I'M STUDYING IS A SPECIFIC GROUP OF PEOPLE CHRONIC PAIN THAT USE DIGITAL HEALTH TRACKERS, THIS IS NOT EVERYONE THAT HAS CHRONIC PAIN IN THE UNITED STATES BY NO MEANS. WAS INTERESTING TO SEE, THE BURDEN OF PAIN, BE ABLE TO DEMONSTRATE CONFIRM PREVIOUS LITERATURE IN THE WILD SETTING IS BURDEN OF PAIN FOR DIFFERENT RACES GO ABOVE AND BEYOND DIFFERENT LEVEL OF PHYSICAL ACTIVITY. REALLY TELLS YOU THE EXPERIENCE OF PAIN IS AN INDIVIDUAL ONE. WHEN WE WANT TO MEASURE IT WE NEED TO CONSIDER THAT PAIN PERCEPTION IS HIGHLY INDIVIDUALIZED LIKE IT DEPENDS ON THINGS LIKE RACE. THOSE THINGS HAVE TO BE TAKEN INTO CONSIDERATION. TO MAKE TREATMENT RECOMMENDATION THAT ARE SENSIBLE TO THE INDIVIDUAL LIKE WE DON'T HAVE TO BE COLOR BLIND OR ERASE VARIABLE WE HAVE TO CONSIDER THEM ESPECIALLY, ESPECIALLY IF WE HAVE AUTOMATIC DECISION MAKING ALGORITHMS WHICH COULD DISTRIBUTE INEQUALITY AT A VERY LARGE SCALE. THERE IS A LOT TO DO, THAT'S REASON I'M HERE IS TO EXTEND THE INVITATION TO ANYONE WHO WANTS TO WORK ON THIS DATA SETS TO LET'S GET TOGETHER, LET'S PROPOSE IDEAS. I HAVE SHOWN THE TIP OF THE ICEBERG OF THE DATA WE COLLECTED. SO WEARABLE QUESTIONNAIRES ON VALIDATED INSTRUMENTS OF MENTAL HEALTH, VALIDATED INSTRUMENTS ON QUALITY OF LIVING. EFFECTIVENESS MEDICATION BUT IN REALITY FOR SUB COHORTS WE ARE ALSO COLLECTING IMMUNOASSAYS, WE ARE COLLECTING DAILY QUESTIONNAIRES OF MIGRAINE STATUS, COLLECTING VOICE, SUB COHORTS BUT THERE'S ADDITIONAL COLLECTION GOING ON THAT I HAVEN'T SHOWN TODAY AND I WILL BE EXCITED TO REPORT ABOUT IN THE FUTURE. SO IF YOU HAVE IDEAS, IF YOU HAVE IDEAS FOR ADDITIONAL DATA COLLECTION THIS POPULATION IS NOT ONLY RECONTACTABLE BUT FULLY ENGAGE WITH THE RESEARCH. SO IT'S WE CAN BUILD A CONTINUOUS RESEARCH EXPERIENCE WITH THEM. SO BACK WITH MORE QUESTION IS WHERE WE WANT TO GO IN THE FUTURE. THANK YOU. [APPLAUSE] >> WEAVED ABOUT 20 MINUTES FOR QUESTIONS SO I'LL OPEN TO THE GROUP TO SEE IF ANYONE WOULD LIKE TO ASK ANY OF THESE PANELISTS ANY QUESTIONS. >> FOLLOWING UP WHAT KAREN SAID ABOUT THE IMPORTANCE OF LOOKING AT THE E CONO METRIC PROPERTIES OF SENSORS WHEN YOU TAKE IN DATA, FROM CONSUMER LEVEL ACTION DO YOU DO ANY CORRECTIVE ACTION FOR CONSUMER RELIABILITY AS MUCH >> BETTER NOW? I GET THAT QUESTION A LOT. THAT WILL BE AN UNDERSTATEMENT. OF COURSE THE VALIDITY OF THIS SENSOR IS TO BE DEMONSTRATED. IS DEAF MITTLY TO BE DEMONSTRATED FOR END POINTS THAT GO TOWARD DIRECTION OF SOMEONE WAS TRYING TO MEASURE AMPLITUDE OF MEASUREMENTS LIKE SPEED OF GATE, THOSE THINGS ARE COMPLETELY NOT POSSIBLE. BUT WHEN YOU ARE TRYING TO ESTIMATE AVERAGE MOBILITY OF AVERAGE LEVEL OF ACTIVITY OVER LONG PERIOD OF TIME, THEN THOSE ARE MORE RELIABLE. IF YOU DO CORRECTION OF KIND OF SHOW SO MAKE SURE THEY ARE NOT TOO MANY HOMES. MAKE SURE THERE'S -- TOO MANY HOLES. YOU TRY TO TAKE THE SAVAGER SO WE HAVE DEVISED A WHOLE SET OF DATA VERIFICATION AND VALIDATION TESTS FOR THIS KIND OF COMMERCIAL WEARABLE DATA THAT ALLOWS YOU TO DO VERY BASIC INFERENCES LIKE THE ONE I SHOWED. >> VERY INTERESTING PRESENTATIONS. THANK YOU VERY MUCH. I'M CURIOUS, SO VERY CLEAR THAT THE DATA -- THE ACQUISITION PROCESSES ARE THERE. AND WORKING WELL. TRYING TO BRING THIS NOW TO THE CLINIC, I KNOW THE CAPTURE IS IN THE HOME ENVIRONMENT BUT TRYING TO -- AND EVEN FOR SOME OF THE PET DATA, WHAT ARE SOME OF YOUR THOUGHTS ON HOW TO REDUCE THE DATA IN TO VARIABLES THAT CAN BE IMPORTED INTO DECISION MAKING TOOLS THAT A CLINICIAN AND PATIENT WOULD HAVE IN A CLINIC? SO ARE THERE THOUGHTS AND ARE THERE WORK BEING DONE TO TRY TO REDUCE SOME OF THIS, TO A POINT WHERE A CLINICIAN, A PATIENT CAN SEE A SCORE ON STEPS OR WHAT HAVE YOU. AND WHAT BARRIERS ARE YOU FACING IN GETTING THINGS INTO CLINICAL RECORD? WHAT WOULD BE HELPFUL IN THAT AREA? >> I'M SURE OTHERS HAVE THOUGHTS AS WELL BUT I CAN TELL YOU WEARABLE DEVICES ARE STARTING TO SEE LARGE META ANALYSIS, THE MOST RESEN IS FALL RISK AND INERTIAL BASED SENSORS AND FROM THERE WE GET A SHORT LIST OF KEY VARIABLES AND THE NEXT STEP NOW IS TO VALIDATE THOSE CLINICALLY. FOR PHYSICAL THERAPY, NOTHING TO CLINICAL PRACTICE UNTIL THERE'S A GUIDELINES BY ATPA. SO I THINK NEXT WORK IS TO SORTS OF DO THAT AND GET THEM ON BOARD. I STARTED TAKING A GRASSROOTS APPROACH, I TEACH A CLASS ON PATHOKINESIOLOGY, AND I TELL MY STUDENTS WE WILL GO TO LAB AND USE THIS TECHNOLOGY BECAUSE IN THE NEXT FIVE YEARS YOU WILL SEE TOOLS IN CLINIC WILL PURPORT TO DO THIS AND YOU NEED TO UNDERSTAND WHAT THE LIMITATIONS ARE NOW SO YOU CAN GET A SENSE WHAT THE MESSAGE I GET FROM CLINICIANS EVERY TIME I SHOW THEM THESE ARE THE THINGS I CAN MEASURE FOR YOU, THEY GET EVEN THE SHORTENED BRIDGED REPORTS I TAKE OUT OF SOMETHING LIKE THE APDM SOFTWARE THAT ARE VERY MUCH DESIGN WITH A CLINICIAN IN MIND, IT WILL REDUCE ALL THAT DATA DOWN TO SOMETIMES AS MUCH AS 30 VARIABLES SO THE STUDENTS LOOK AT THAT REPORT AND SAY THAT'S COOL BUT WHAT DO I DO, WHERE DO YOU LOOK? IT'S NOT AN UNCOMMON PROBLEM. PEOPLE HAVE DONE INSTRUMENT AND GATE ANALYSIS LIKE SHRINERS HOSPITAL DOES MOTION CAPTURE FOR GATE AND HAVE BEEN FOR 20, 30 YEARS NOW. THOSE REPORTS COME OUT SAME THING, THE QUESTION IS IT'S TRAINING CLINICIANS WHERE TO LOOK IN THE DATA. SO WE NEED TO START BY STUDYING IT, FINDING THE PARAMETERS, GOING BACK AND CORRELATING THOSE WITH THE ACTUALIOUS COMES TO PREDICT BEHAVIOR AND INCORPORATE THOSE INTO THE CLINICAL PRACTICE GUIDELINES. BUT THERE'S MUCH WORK TO BE DONE, THERE'S NOT A SOLID FRAMEWORK TO DO IT YET, AT LEAST NOT IN PHYSICAL THERAPY, I CAN'T SPEAK FOR OTHER FIELDS. >> MAYBE JUST A QUICK COMMENT. THE WHOLE QUESTION ABOUT VALIDITY AND HOW THIS DATA SHOULD BE PROCESS AND DONE USED TO EXPLAIN AND MAKE DECISION ON BUT MAYBE THERE'S AN OVERARCHING THEME OF DATA USE THAT ACTUALLY COULD DECIDE WHERE DATA SHOULD SIT AND HOW IT SHOULD BE COLLECTED AND AGGRAVATED SO YOU SEE TWO TRENDS THERE, YOU SEE THE EHR SYSTEM, TRYING TO GET WEARABLE DATA AND THEN YOU SEE HUBS IN THE CONSUMER WORLD LIKE APPLE HEALTH, TRYING TO GET EHR IN. PERSONALLY AND PROBABLY AS COMPANY WE ARE FOCUSED ON GETTING THE PATIENT THE PARTICIPANTS CONTROLLING THEIR OWN DATA SO WOULD BE NICE IF FUTURE EVERYONE HAD THEIR OWN HEALTH ROLES IN THEIR PHONE AND CAN GO TO CLINICIAN AND DISCUSSION THIS DATA TOGETHER. THAT IS ASPIRATIONAL, IT COMES BACK TO THE ORIGINAL CONCEPTS, WHAT'S IN A NUMBER, HOW THAT NUMBER IS GENERATED. I THINK PATIENTS AND CLINICIANS WHEN THEY HAVE 30 VARIABLES TO LOOK AT AND TRY TO INTERPRET, IT'S DIFFICULT. BUT IF THERE IS SOME TYPE OF METRIC WHICH PROVIDS A VALID NUMBER OF WHATEVER MEASUREMENT YOU ARE TRYING TO TAKE, MAYBE NOT GET INTO ALL THE UNDERLYING COMPONENTS IT MAY HAVE GREATER UPTAKE IN THE CLINICAL SETTING. >> I WANTED TO CONGRATULATE YOUR TALK KAREN, IT WAS FASCINATING AND VERY EXCITING WHEN YOU THINK ABOUT FUTURE AND KINDS OF THINGS WE CAN DO. ONE OF THE POPULATIONS I WORKED WITH A LOT IS PEOPLE WITH OSTEOARTHRITIS. YOU MAY BE FAMILIAR WITH MICROCLOUT SEINESS THAT WAS COIN AD NUMBER OF YEARS AGO TO REFER TO ADJUSTMENTS IN MOVEMENT PATTERNS THAT PEOPLE MAKE WHEN THEY DEVELOP OA, APPARENTLY SOME PEOPLE ARE PRONE TO ENGAGE IN THESE BEHAVIORS WHICH IN TURN ALTERATIONS HOW THEY WALK BELIEVE CONTRIBUTE TO PROGRESSION OF THE DISEASE. I HAVE BEEN FASCINATED WHAT'S GOING ON THERE, PERCEPTIONS OF PAIN, DOES OTHER PAIN, PSYCHOLOGICAL FACTORS PLAY A ROLE IN THOSE PEOPLE, SO ON. THE EXCITING PART OF MONITORING THESE PATTERNS EARLY IS THE POSSIBILITY FOR PREVENTION IF THAT INDEED IS PREDICTOR OF LATER PROBLEM. SO I'M WONDERING IS ANYBODY WORKING WITH THESE SENSORS IN PREVENTION WAY TO CAPTURE PEOPLE EARLY WITH OA OR OTHER CONDITIONS, IN A WAY TO ALTER PROGRESSION OF THE CONDITION? >> I CAN'T SPEAK DIRECTLY TO OA, I HAVE NOT DONE A LOT OF WORK MANY THAT FIELD. I WOULD EXPECT CERTAINLY THERE'S SOME HAPPENING BECAUSE THERE'S MONITORING OF THINGS LIKE DYNAMIC LOAD AND USING THAT AS A SCREENING FOR PREVENTION OF ACL INJURY, A PRE-CURSOR TO OA IN SOME CASES. I CAN TELL YOU FROM OTHER FIELDS LIKE STUDY I WAS INVOLVED IN ON MULTIPLE SCLEROSIS, THAT WAS THE INTENT, THAT WAS A UNIQUE POPULATION. SO FOR MS THEY RATE SEVERITY OF DISEASE ON THE EDSS SO THESE WERE ALL PEOPLE EDSS I WANT TO SAY UNDER 25, VERY MILDLY IMPAIRED IN TERMS OF GROSS FUNCTION. SO THAT WAS INTEREST OF NEUROLOGIST LEADING THE CHARGE, TO SEE ISSUES IN BALANCE AND GATE PARAMETERS HIS CLINICAL TESTS WEREN'T PICK UP HE SUSPECTED HE COULD HONE IN ON MOVEMENT IMPAIRMENTS HAS BEEN RENT MOVEMENT PATTERNS WHATEVER TERM YOU LIKE EARLIER AND MANAGE THOSE WITH TREATMENT AND PHARMACOLOGY THINGS LIKE THAT IN TERMS OF BETTER OUTCOMES. THAT'S WHAT WE SHOW THE 25-FOOT WALK TEST IS PRIMARY MEASURE OF FUNCTION OTHER THAN QUESTIONNAIRE BASED DATA DIDN'T DO IT, DIDN'T GIVEN ENOUGH GRANULARITY BUT BALANCED DATA DID SO IT'S HAPPENING IN VARIOUS POPULATIONS, THE PROBLEM WITH PREVENTION IS THAT UNTIL YOU KNOW WHAT PROGRESSION AND WHAT BOX THEY FALL IN, CHRONIC LOW BACK PAIN WE HAVE THE ISSUE ARE PEOPLE SUPER LOOSE AND UNSTABLE, WHICH IS WHAT THE MSI BASED TREATMENT APPROACH TELLS YOU AND YOU HAVE ANOTHER CAMP OF PEOPLE STILL AND NOT MOBILE ENOUGH TO TEACH TO RELAX AND DO MORE BEHAVIOR GRADED EXPOSURE, SO THEY CAN EXPLORE RANGE OF MOTION. THAT'S A SIMPLISTIC DEFINITION OF TWO DISTINCT TYPES OF LOW BACK PAIN. THERE'S HETEROGENEITY TO UNDERSTAND WHAT MOVEMENT PATTERNS ARE THERE, WHICH ONES CAN CONTRIBUTE TO PAIN PERCEPTION, PAIN BEHAVIOR, WHICH DON'T BEFORE WE START TO SCREEN FOR THOSE EARLIER. I THINK THAT'S SORT OF WHERE THE MUSCULOSKELETAL CONDITIONS, THAT'S WHERE WE ARE. BUT I CAN'T SPEAK DIRECTLY TO OA. I EXPECT THEY ARE IN A SIMILAR AREA, THESE ARE SIMPLER TO HONE DOWN TO BE AHEAD OF THE CURVE ON THAT I WOULD EXPECT. >> THANKS TO ALL THREE, GREAT TALKS. JUST WANT TO I GUESS FOLLOW-UP ON A POINT ABOUT INTERPRETATION OF THIS DATA BECAUSE I KNOW IN MY OWN WORK WE STRUGGLE WITH BOTH HOW TO INTERPRET INTENSITY OF MOVEMENT INTO CATEGORIES OF SEDENTARY VERSUS MODERATE EXERCISE BECAUSE NORMS DON'T EXIST ACROSS AGE GROUPS CONSISTENTLY IN THE FIELD. BUT SIMILARLY FOR PERFORMANCE BASED MEASURES, I'M NOT AWARE OF ANY NORMS IN KIDS FOR EXAMPLE SIT OR STAND OR METERED WALK. BUT WANT TO ASK HOW MUCH IS DONE IN PROVIDING NORMATIVE VALUES BY AGE AND SEX AS WELL AS BY CONDITIONS AND WHERE ARE THOSE GAPS THAT YOU SEE. >> GOOD ONE. I TRY TO STICK WITH ADULTS PERSONALLY BECAUSE THEY COME CLOSER AND CHRONIC LOW BACK PAIN IS BIGGER POPULATION THOUGH I WILL TELL YOU I HAVE DONE A RECENT STUDY I HAD AN AVERAGE AGE OF 22, THESE PEOPLE HAD SEVEN YEARS OF EXPERIENCE OF LOW BACK PAIN SO THERE'S A NEED TO LOOK AT YOUNGER POPULATIONS, CERTAINLY A MESSAGE OF TAKEN FROM THIS WEEKEND. I THINK THAT ENOUGH SOME OF THE MORE STANDARDS DISTANCE TIME WALK TEST AND THINGS LIKE THAT, SOME AGE NORMATIVE DATA AND COLLEAGUES IN PEDIATRICS ARE HOLLERING AT ME TELLING ME WHICH ONES BUT THEY ARE FEW AND FAR BETWEEN. THESE IF YOU THINK ABOUT POPULATION SEEKING TREATMENT FOR THESE CHRONIC CONDITIONS, SUCH A SMALL NUMBER AND SUCH A SMALL FOCUSED GROUP WITHIN THE THERAPY WORLD WE JUST DON'T HAVE LARGE ENOUGH NUMBERS TO GET TO THOSE DATA YET. THE IDEA OF SOMETHING LIKE WEARABLES LARGE DATA TRACKING LIKE LUCA IS DOING WOULD BE A GREAT WAY TO TARGET THE DATA AND FIND FOR ACTIVITY LEVEL LUCA'S PLATFORM WOULD BE A GREAT WAY TO GO AFTER THAT, THE PRIVACY CONCERNS WITH CHILDREN ARE WHOLE OTHER GLAD THE LAWYERS ARE NOT HERE TO HEAR ME SUGGEST THAT BUT IT WOULD BE A RICH DATA SET TO EXPLORE TO GET TO THAT QUESTION. THAT'S THE PROBLEM, IT'S RELATIVELY SMALL PORTION OF CHRONIC PAIN, A SMALL PORTION OF REHAB AND SPREAD OUT THROUGH THE U.S., RESEARCHERS ARE HAVING TROUBLE GETTING ENOUGH PEOPLE IN THE DIFFERENT AGES TO ACCOUNT FOR THE FUNDAMENTAL CHANGES BUT IT'S ABSOLUTELY IMPORTANT AND NEEDS TO BE DONE. >> I KNOW OCCUPATIONAL THERAPY WE LOOK AT COMPENSATORY STRATEGIES. NOT EVERYONE IS GOING TO HAVE A TYPICAL MOVEMENT PATTERN. THE DISEASE PROGRESSION, IT'S UNPREDICTABLE SO I'M WONDERING EVEN WITH BIG DATA PLATFORMS, IF YOU CAN LOOK AT ACTIVITY BASED ON ACTIVITIES OF DAILY LIVING OR WHAT IS MEANINGFUL TO PEOPLE AND HOW DO PAY RATINGS CHANGE THERE. BECAUSE IT'S -- DOESN'T ALWAYS FOLLOW THESE STANDARD PATTERNS. >> ONE THING I WAS GOING TO SAY, MAYBE WE HAVE THE OPPORTUNITIES HERE TO THROW NORMATIVE DATA OUT OF THE WINDOW. SINCE YOU HAVE CONTINUOUS DATA THE NORMATIVE DATA CAN BE YOURSELF IN THE PAST. YOU CAN LOOK AT CHANGES WITH YOURSELF IN THE PAST. NORMATIVE DATA IF IT'S BASED ON AGE AND GENDER YOU SHALL USUALLY IS BROKEN DOWN BY THAT'S REALLY NOT ENOUGH, PAIN IS AS WE SAID REALLY PERSONAL EXPERIENCE. RACE SHOULD BE ANOTHER DIMENSION NOW. EVERYTHING ELSE YOU ARE DOING SHOULD BE ANOTHER DIMENSION. SO IF YOU HAVE THE OPPORTUNITY TO BE ABLE TO STANDARDIZE TO YOURSELF, IF YOU HAVE CONTINUOUS DATA THEN YOU GET VALUE BETWEEN 0 AND 1 THAT TELLS YOU HOW WHAT YOUR CHANGE IS COMPARED TO WHERE YOU ARE. >> THAT WAS A BIG TAKE HOME FROM LUCA'S TALK, WE TALK SO MUCH ESPECIALLY YESTERDAY ABOUT WE HAVE A HARD TIME UNDERSTANDING WHERE PEOPLE START BECAUSE BY THE TIME WE SEE A CHRONIC PAIN PATIENT THEY HAVE DEVELOPED A LOT OF PAIN BEHAVIORS PARTICULARLY COMPENSATION SO WE DON'T KNOW WHERE WE STARTED AND WITHOUT KNOWING WHERE YOU START IT'S HARD TO KNOW WHERE YOU ARE GOING SO THE ABILITY TO LOOK BACK AND SAY SIX MONTHS AGO BEFORE I HAD ISSUES OF PAIN, THIS IS HOW MUCH I MOVED WHERE I MOVE, THIS IS REAL POTENTIAL TO GROW THAT WAY. I KNOW ALSO IN PHYSICAL THERAPY, SOME OF THE CLINICAL TRIALS LOW BACK PAIN WE USE PATIENT SPECIFIC FUNCTIONAL SCALE WHICH AGAIN IT IS NOT THE MEASURE ON PAIN BUT IT ADDS A NICE DIMENSION TO PAIN DATA BECAUSE IT ROUTES -- TRIES TO BASE TREATMENT IN ACTIVITIES THAT ARE MEANINGFUL TO THE PATIENT. SO WE WERE IN VERMONT, WE HAD PEOPLE WHO WANTED TO GET BACK SKIING OR GARDEN OR WANT TO RIDE BAKE TO FARMERS MARKET SO THOSE ARE GOALS YOU SET WITH THE CLINICIAN. AND PART OF THE TREATMENT TAILORING IS THEN MAKING SURE THAT YOU ARE DOING REHABILITATION EXERCISES THAT WILL HELP YOU ADDRESS TO NOSE GOALS. WE DIDN'T HAVE LARGE ENOUGH DATA SET TO STRATIFY BASED ON WITH AND WITHOUT PATIENT SPECIFIC FUNCTIONAL SCALE AND ANECDOTALLY THE PATIENTS SAID THEY APPRECIATED THAT COMPONENT TO THE TREATMENT. AND THEY SAW VALUE IN THAT AND HELPED THEM FEEL LIKE THE CLINICIAN WAS REALLY TAKING INTEREST WHAT THEY NEED TO DO AND PUTTING THEIR MOVEMENT GOALS FIRST. SO THERE'S SOME TENDENCY TO THAT AS WELL. >> A TECHNICAL QUESTION FOR CLAS. I'M INTERESTED IN MICROGLIAL ACTIVATION. AND PBR 28. I JUST DROVE ASKING THE QUESTION, THIS IS IMPLICATIONS OF COURSE FOR NOT JUST PAIN BUT FOR CENTRAL NEURODEGENERATIVE DISEASE LIKE ALZHEIMER'S DISEASE, PARKINSON DISEASE. MY UNDERSTANDING IS THAT WITHIN THE POPULATION, THERE ARE LOW AFFINITY AND HIGH AFFINITY BINDERS TO TRANSLOCATED PROTEIN. WHERE PBR 28 BINDS. WONDERING HOW YOU TAKE THAT INTO ACCOUNT IN STUDYS? >> YOU CAN HAVE BASICALLY 0 AFFINITY LOW OR HIGH AFFINITY, IT'S A POLYMORPHISM, SO WE ACCOUNT FOR THAT BY EXCLUDING THE LOW AFFINITY. WE ONLY MEDIUM TO HIGH AFFINITY BINDERS. IN THIS POPULATION WE -- THE DATA I SHOW WAS BASED OFF OF 14 PATIENTS. I DID NOT INCLUDE THAT AS A CO-VARIANT ANALYSIS BECAUSE YOU DON'T WANT TOO MANY -- WE HAVE SO MANY OTHER THINGS GOING ON SUCH AS LEVEL OF INJURY AND TIME INJURY. THAT'S ONE VARIABLE WE WANT TO INCLUDE. SO GOOD THING LONGITUDINAL DATA IS THAT WE CAN -- WITHIN SUBJECT CONTROL FOR THAT. >> QUESTION FOR LUCA. I'M WONDERING IF YOU THOUGHT ABOUT ADS BILL MENTIONED, LOOKING AT PREDICTIVE VALUE OF THE DATA THAT YOU HAVE AND THE REASON I ASK IS BECAUSE FAMILIAR WITH ANOTHER COMPANY THAT'S DONE WORK IN DEPRESSION AND THEY TRACK DIFFERENT DATA, PASSIVE DATA OFF THEIR iPHONES SO HOW LONG ARE THEY TEXTING HOW FAR FROM HOME, ARE THEY SLEEPING OR NOT BUT THEY ARE ABLE TO PREDICT LONGITUDINALLY FULL 24 HOURS BEFORE DEPRESSION PATIENT SPIRALED. AND THE DATA FED BACK INTO A LARGE HEALTHCARE CLINICK THEY HAD A NURSE CARE MANAGER WHERE THEY CHECK IN BE PATIENTS PREVENTIVELY AND SAY WHAT'S GOING ON AND DO A CLINICAL INTERVENTION. THEY SHOW OVER TIME ABLE TO REDUCE HOSPITALIZATIONS, ER VISITS, IMPROVE DEPRESSIVE SYMPTOMS AND MANAGEMENT OF MAJOR SPIRALS. SO I CAN REALLY SEE AN AREA LIKE THIS BEING VALUABLE FOR TRAIN, WHETHER ACTIVITY TRACKING ACTIVITY DATA OR COMBINATION OF BOTH, WHERE YOU HAVE PREDICTIVE VALUE AND ALERT THEM THEMSELVES, CHECK IN BEFORE A PATIENT MAY BE EXPERIENCING A SEVERE SPIRAL. I'M CURIOUS IF YOU THOUGHT ABOUT THAT OR DOING WORK IN THAT AREA. >> Q. I'M FAMILIAR WITH THE WORK YOU ARE MENTIONING. THERE'S WORK IN MENTAL HEALTH, THERE'S STRONG SIGNALS THERE IF YOU HAVE ABILITY TO GATHER THE DATA FROM SOMEONE'S PHONE, ESPECIALLY LOCATION IS ONE OF THE TELLING ONE WHERE PEOPLE SPEND TIME. PAIN IS DIFFERENT IN THE SENSE MORE HETERO GENIUS, CHRONIC PAIN, IT'S CHRONIC, ALWAYS THE SAME AND WHERE YOU CAN MAKE A DIFFERENCE IS CONDITION WHERE YOU HAVE FLAIR UPS, AND SO WE WORK AD LITTLE BIT ON MIGRAINES SPECIFICALLY. WHICH IS PREVALENT IN OUR POPULATION, 461% HAS SUFFERS FROM MIGRAINES. THERE ARE -- I CAN SAY THE WORK IS EARLY ON AND THERE'S NOTHING PUBLISHED YESTERDAY SO I HAVE TO BE HIGH LEVEL BUT IT IS -- THE TRIGGERS USUALLY REPORT AS BEING TRIGGERS THEY FEEL FOR MIGRAINE WHICH TENDS TO BE STRESS, LACK OF SLEEP AND ENVIRONMENTAL. THEY CAN DETRACT BY PHONE AND BY WEARABLE DEVICE AND THOSE CAN GIVE THE SAME LEVEL OF SIGNAL THAT YOU WERE MENTIONING FOR MENTAL HEALTH CONDITIONS. SO ABILITY OF INTERVENTION THERE IS NO MUCH MORE OF GOING TO THE CLINIC AND PREVENTING AN ER HOSPITALIZATION BECAUSE THAT DOESN'T HAPPEN WITH MIGRAINE BUT IS REALLY MUCH MORE ABOUT INFORMING SOMETHING IS GOING TO HAPPEN SO YOU CAN CHANGE PLAN FOR THE NEXT DAY, WHICH IS POSHES IN QUALITIES OF LIVING. >> RELATED TO THAT, HAVE YOU LOOKED AT -- I KNOW SOCIAL MEDIA HAS BEEN USED AS PREDICTOR. POSH RELAPSE AND THINGS LIKE THAT. ANY ONGOING WORK LOOKING AT WHAT PEOPLE ARE POSTING ON SOCIAL MEDIA OR SEARCHING ON THE WEB? >> NOT BY US. I THINK THERE'S SOMETHING GOING ON AROUND THE SENT KNOLL PROGRAM MIGHT BE LOOKING AT SOMETHING LIKE THAT IN CONTEXT OF ADVERSE EVENT MONITORING BUT NOT ANYTHING MANY THAT DIRECTION. >> SOCIAL MEDIA, IF YOU GO BACK TO PRIVACY CONCERN, SOCIAL MEDIA IS A DATA IN RESEARCH STUDY THE PERSON IS NOT SO WILLING TO CONTRIBUTE. IN OUR EXPERIENCE. >> >> I HAVE SEEN STUDIES THEY WEREN'T AWARE THEY WERE PARTICIPATING. >> THAT'S THE PROBLEM, WE DON'T DO THOSE STUDIES. MIGHT BE THE SHORT ANSWER. >> THIS IS GREAT. LOT OF EMERGING TECHNOLOGIES IN FASCINATING TO UNDERSTAND HOW FAST THE DEVELOPMENT OF THESE TECHNOLOGIES HAVE GONE ON AND THE VALIDATIONS HAVE LAGGED BEHIND. SO IT'S GOOD TO SEE THAT HERE REFLECTED. THE QUESTION THAT I HAD IS IN TERMS OF FALSE POSITIVES AND HOW BEST DO YOU REALLY ASSESS THAT, ARE YOU REALLY MONITORING AND HOW DO YOU HAVE THOSE CHECKS AND BALANCES ON FALSE POSITIVE? >> FALSE POSITIVES ARE A BIG PROBLEM. WE DON'T HAVE ANY PRODUCTION PREDICTION SYSTEM AT THIS POINT SO IT'S NOT DODGE CERTAIN RIGHT NOW BECAUSE WE ARE NOT DEVELOPING THAT YET. IF YOU GO THAT DIRECTION IT'S PROBABLY THE MAIN THING TO CARE ABOUT AND SOMETHING I FEEL LIKE SOMETIMES THERE'S BLANKET STATEMENT WHAT IS A FALSE POSITIVE IS AND WHAT IS BAD OR GOOD BUT DEFENDS APPLICATION. IF YOU HAVE A PRE-SCREENING SYSTEM LIKE ECG APPLE WATCH YOU CAN TOLERATE HIGHER BECAUSE THE NEXT IS YOU HAVE TO TALK TO SOMEONE WHO WILL LOOK AT YOU BUT IF IT'S IN ICU IN CLINIC SYSTEM THAT NEEDS TO GO UP WHEN HAVING SEPTIC SHOCK THAT'S A DIFFERENT SORRY SO THE SHORT ANSWER, WE DON'T HAVE PREDICTIVE SYSTEMS IN PLACE YET SO WE DON'T TACKLE THAT YET, IT'S REALLY APPLICATION SPECIFIC. >> TRYING TO WRAP THIS UP AT TEN O'CLOCK BUT I WILL JUMP IN ANYWAY. SO IN PREPARATION FOR THIS MEETING I ASSUMED WE WOULD HEAR ABOUT USE OF SENSORS FOR FUNCTIONAL INTERFERENCE AND IMPAIRMENT SOME OF WHAT YOU HAVE PRESENTED MAKES ME THINK THAT MAYBE THERE'S SOME SIGNAL THERE FOR PAIN INTENSITY LOCATION EVEN QUALITY CERTAIN LEVEL. I'M PROBABLY REACHING THERE AND YOU DON'T WANT TO REACH BUT SOME OF THE EARLY NUANCE COMPENSATORY MOVEMENTS, SOME OF THE STUFF YOU HAVE GOTTEN, THE PET SCAN WORK, CAN JUST TALK A MINUTE ABOUT IS THAT REACHING TOO FAR? ARE THERE POSSIBILITIES ASSESSING PAIN INTENSITY AND INFER BACKWARDS FROM SOME OF THE EARLY THINGS YOU ARE SEEING? >> FROM THE PET DATA, WHAT WE DID IS WE -- IN THE SPRAINED ANKLES WE SCAN PATIENTS AND THEN I ASK THEM AND PALPATED THE PATIENTS, AND THEN I WENT AND LOOKED AT THE SCAN. AFTER LOOK AT IF SCAN YOU CAN ASK PATIENT WHAT ABOUT YOUR LEFT FOOT, HOW IS YOUR TOE? SURE ENOUGH YEAH MY TOE IS OKAY. BUT HOW DO YOU KNOW AS MUCH SO I THINK IT'S A VERY -- THAT WAS A SENSITIVE MARKER OF NOT JUST THE MAIN INFLAMMATORY RESPONSE BUT WE COULD ACTUALLY GO IN AND POINT OUT THINGS THAT PATIENTS WERE AWARE OF THAT WERE NOT REPORTING. THE FALSE POSITIVE THERE MIGHT BE AN ISSUE. >> I WANTED TO CHIME IN, I PURPOSEFULLY LEFT OUT A HOST OF SENSORS TRACKING PAIN IN IN PATIENTS AND THAT'S A WHOLE SEPARATE FIELD OF STUDY. I STUCK TO WHAT ARE WE USING IN REHAB. THAT'S WHY I WENT FROM A MOVEMENT PERSPECTIVE. THAT IS A TECHNOLOGY BUT I THINK THE INHERENT PROBLEM AND BIAS IS IT IS APP BASED TECHNOLOGY USING THE SAME VAS AND OTHER PAIN MEASURE WITH INHERENT PROBLEMS. THE ADVANTAGE I SEE IS THAT IT IS A UBIQUITOUS WAY FOR RESEARCHERS AND PHYSICIANS TO ASK THOSE QUESTIONS AT DIFFERENT TIMES SO AT HOME IN HOME ENVIRONMENT DOING ACTIVITIES OF DAILY LIVING AND TRYING TO GET A SENSE OF WHERE YOU ARE, MAYBE COMBINING WITH SOME BIG DATA, WHERE IS YOUR LOCATION, HOW MANY STEPS ARE YOU TAKING HAVE YOU BEEN ACTIVE TODAY AND CAN YOU CORRELATE AND TRY TO GET A SENSE OF WHAT THE CURVE OF SOMEBODY'S VAS SCORE IS DURING THE DAY. WHAT ARE THE THINGS TO MAKE REPRODUCIBILITY MAKE IT GO UP FOR INDIVIDUAL PERSON, SO EXPLORING THAT WAY BUT I PURPOSEFULLY IGNORED THAT CAN OF WORMS FOR THAT SPECIFIC REASON. >> JUST A QUICK COMMENT ABOUT ASSESSMENT OF PAIN INTENSITY. FUNCTION AND ENJOYMENT IN IN LIFE, THE NATIONAL PAIN STRATEGY IS ADVOCATING THE THREE ITEM PEG IT IS VERY QUICK, EASY FOR i PHONES AND MAYBE A ME RICK YOU CAN USE TO LOOK FOR RELATIONSHIPS OR SIGNALS WITH INTENSITY FUNCTION AND ENJOYMENT IN LIFE. A SIMPLE 0 TO 10 SCALE, THOSE THREE DOMAINS. >> VERY INTERESTING. THANK YOU FOR SUGGESTING. A QUICK COMMENT, TO THE COMMENT AND TO THE POINT MADE EARLIER. I MISS AD FULL DAY OF WORKSHOP SO MAYBE THIS POINT WAS IT RATED YESTERDAY. BUT MY FEELING, WHAT WE SEE IN THE DATA, PAIN EXPERIENCE IS REALLY FUNDAMENTALLY A PERSONAL THING, NOT SOMETHING THAT CAN BE INFERRED FROM SENSOR, NOT SOMETHING THAT WE WILL BE ABLE TO INFER EVEN IF ABLE TO MEASURE EVERYTHING IN THE FUTURE. SO SIT'S MORE EMOTION, YOU CANNOT PREDICT EMOTION EVEN IF YOU HAVE MRI. YOU CAN TELL POE LAYERTY HAPPY AND SAD BUT CAN'T TELL PERTINENT VERSUS ANNOYED THAT IS DEEPLY DEPENDING ON SO MANY OTHER THINGS NOT MEASURABLE. SO WE THINK MORE AUGMENTING REALLY THINK PANT ADDING ANOTHER DIMENSION TO SUBJECTIVE PAIN WHICH COULD BE YOUR FUNCTIONAL MOBILITY WHICH COULD BE MEASURE OBJECTIVELY AND THEN YOUR OVERALL NUMBER TO DEVELOP A DRUG COULD BE THE AREA IN THAT PLANE DEFINE BID SUBJECTIVE AND OBJECTIVE MEASURE. BUT SUBJECTIVE IS NOT GOING TO GO AWAY, CAN'T GO AWAY. >> ARE YOU SEEING CHANGES IN YOUR METRICS DRUGS, I SAW YOU HAD DATA ON PRESCRIPTION AND NON-PRESCRIPTION MEDICATIONS BE ABLE TO TRACK WHEN THEY TACK THEM AND HOW THAT CHANGES BEHAVIOR? >> NOT IN THE STUDY BUT WE HAVE DONE OTHERS THAT ARE NOT PUBLISHED IN WHICH WE WERE LONGITUDINALLY WITHIN SUBJECT TRACKING PERCEPTION OF PAIN AND INTERVENTIONS IN THE -- THERE WERE A FEW OF THEM, DIGITAL HEALTH APPS WERE ONE OF THEM, OVER THE COUNTER MEDICATION IS ANOTHER ONE. NOT TALK TOO MUCH ABOUT THAT, THE PAPERS IN DISCUSSION BUT YEAH, YOU CAN SEE LIKE WHEN YOU GO TO INDIVIDUAL LEVEL YOU CAN SEE SIGNIFICANT CHANGES IN BPI DEPENDING INTERVENTION YOU DO BUT IF YOU GO BACK TO CROSS SECTIONAL LEVEL THERE'S SO MUCH NOISE YOU CAN'T TELL. >> THANK YOU AGAIN TO OUR PANELISTS. [APPLAUSE] I'M DAVE THOMAS, OFFICE OF WOMEN'S RESEARCH WOMEN'S HEALTH AND FOUNDING MEMBER OF THE NIH PAIN CONSORTIUM. I WANT TO THANK WENDY BILL AND OBSSR FOR THIS REALLY INTERESTING MEETING, FASCINATING AND IT'S SO IMPORTANT, YOU GUYS ARE LEADING CHARGE TO MAKE SURE WE LOOK -- WHEN LOOKING AT SPAGHETTI WE LOOK BEYOND JUST BIOLOGICAL, IT'S SO MUCH MORE WITH PAIN, THE WHOLE PICTURE. OUR FIRST SPEAKER IS DR. DR. ROY FREEMAN, TOLD ME NOT TO SAY TOO MUCH, HE'S DIRECTOR AND PROFESSOR OF NEUROLOGY, AT THE CENTER FOR AUTONOMIC AND PERIPHERAL NERVE DISEASE AT BETH ISRAEL DEACONESS CENTER AUTONOMIC NERVOUS SYSTEM. OKAY. HE'S ALSO EXECUTIVE COMMITTEE OF THE ACTION GROUP SO >> FOR THOSE INTERESTED THERE'S DETAIL ON THE HAND OUTS FOR THOSE NOT INTERESTED THEY HAVE TESTING WIT H FOCUSING ON BACKSIDE, MY DATES CLOSURES. LET ME BEGIN WITH BACKGROUND, THIS IS A PSYCHOPHYSICAL TEST WHICH IS TO SAY THAT IT IS SUBJECT TO -- WE WERE TALKING ABOUT REFORMULATING SUBJECTIVE GIVING IT A NEW NAME. THIS IS A NAME THAT DATES BACK 150 YEARS. IT APPLIES FOR A GROUP OF TESTS WHICH POSSIBLY MOST ARE MORE FAMILIAR WITH THEM, SENSORY TESTING ODOMETRY FOR EXAMPLE, VISUAL TESTING, AND SENSORY TESTING IS MORE COMPLICATED THAN THESE BUT IT IS WITHIN THE SAME FAMILY. NOW, UNLIKE THE NEUROLOGICAL SENSORY EXAMINATION WHICH IS HETERO GENIUS YOU CAN HAVE TEN NEUROLOGISTS IN THE ROOM, EACH ONE OF THEM WOULD DO SENSORY EXAMINATION IN A SOMEWHAT DIFFERENT WAY. QUANTITATIVE SENSORY TESTING ATTEMPTS TO STANDARDIZE THE TEST, NO T TO REMOVE THE SUBJECTIVITY BUT AT LEAST TO REMOVE THE VARIANT. SO STIMULUS IS STANDARDIZED CALIBRATED CONTROLLED, DELIVERY SYSTEM IS IN ACCORDANCE WITH VERY FIXED ALGORITHMS, THAT DATE BACK A HUNDRED YEARS. I WILL TALK ABOUT THEM BRIEFLY BECAUSE THIS IS RELEVANT WITH RESPECT TO THE CONTRAST BETWEEN LABORATORY BASED AND BEDSIDE SENSORY TESTING. ONE OF THE BIG DIFFERENCES IS THE STATIC VERSUS DYNAMIC. BY STATIC, WE MEAN STIMULUS IS GIVEN, PATER GETS OPPORTUNITY TO SAY WHETHER THEY FEED IT, HOW PAINFUL IT IS, HOW STRONG IT IS VERSUS DYNAMIC WHEN THERE IS A COMPUTERIZED RAM WHICH OCCURS AT A SPECIFIC RATED, ONE DEGREE PER SECOND, AND PATIENT SAYS WHEN THEY FEEL THE STIMULUS. EACH ONE OF THESE DELIVERY SYSTEMS IS IN ACCORDANCE WITH VARIOUS TEST PARADIGMS, I WILL GIVE YOU NAMES. FOR EXAMPLE, THERE IS THE METHOD OF LIMITS WHICH IS THAT GRADUAL INCREASE, THERE'S THE METHOD OF LEVELS WHEN THERE ARE STIMULI ON VARIOUS GRADES GIVEN AND THE PATIENT GETS A CHANCE TO REFLECT AND SAY YES I FEEL THIS OR NO, I DON'T AND HOW STRONG IT IS AND THEN FINALLY THERE IS THE FIRST CHOICE PARADIGM, OFTEN GIVEN TWO INTERVALS WHERE ONE INTERVAL STIMULUS IS GIVEN, ANOTHER THERE IS A NULL STIMULUS AND THE PATIENT IS ASKED TO SAY WHEN THEY PERCEIVE THE STIMULUS. DELIVERY SYSTEM IS STANDARDIZED H IN ACCORDANCE WITH WELL WORKED OUT AL ALGORITHMS AND THE RESPONSES ARE STANDARDIZED AS WELL. SO EVERYTHING HAS MUCH AS POSSIBLE WITH SENSATION IS STANDARDIZED. QUANTITATIVE SENSORY TESTING ALLOWS YOU TO ASSESS LOSS OF FUNCTION AND GAIN OF FUNCTION, DISADVANTAGES ARE THAT ALTHOUGH WE CAN ASSESS VARIOUS POPULATION OF NERVE FIBERS THE LOCALIZING ABILITY IS LIMITED. YOU CAN HAVE A PROBLEM ANYWHERE FROM THE RECEPTOR TO THE CENTRAL NERVOUS SYSTEM AND QUANTITATIVE SENSORY TESTING REALLY NOT DIFFERENTIATE, CORE SUBJECT BIAS AND ATTENTION YOU NEED TO HAVE A WELL FOCUSED AND WELL MOTIVATED PATIENT. FOR THOSE WHO WANT TO READ MORE, THE GROUP PUT TOGETHER A CONSENSUS PAPER TALKING ABOUT IT NOT ONLY IN PAIN BUT ALSO IN FACT QUANTITATIVE SENSORY TESTING IN THE MODERN ERA BEGAN NOT IN THE PAIN FIELD BUT IN THE DISEASE MODIFYING FIELD FOR PERIPHERAL NEUROPATHY, MOST PROMINENTLY DIABETIC NEUROPATHY WHEN THERE WERE VARIOUS STRATEGIES AND I SAY WERE BECAUSE THERE'S NOT MUCH ACTION AT THE MOMENT TO CHANGE NATURAL HISTORY DIABETIC NEUROPATHY. SO TO MOVE FROM THAT, HOW DID IT -- WHAT CAUSE THIS INTEREST WITH RESPECT TO PAIN? IT GOES BACK TO A PAPER WRITTEN BY -- IN FACT EDITORIAL WRITTEN BY MITCHELL MAX AND CLIFF FORD WOLF NOW ALMOST 20 YEARS AGO IN WHICH THEY SPOKE ABOUT MECHANISM BASED DIAGNOSIS. I WILL IN A CARTOON FORM TAKE YOU THROUGH WHAT HYPOTHESES UNDERLIE MECHANISM BASED HYPOTHESES. AND IN ESSENCE IT IS TREATING THE ENGAGEMENT BETWEEN A CLINICAL WITH CLINICIAN AND PATIENT AND A PATIENT AS A MATCH MAKER. OLD STYLE MATCH MAKER FROM THE 18TH CENTURY NOW OF COURSE TAKEN OVER BY NUMBER OF ACTS WHICH PERHAPS WE HEARD A LITTLE ABOUT TODAY. NOT SURE IF THIS IS ONE OF THE POSSIBILITIES WITH THE APP THAT WE HEARD IN THE EARLIER SESSIONS BUT ESSENTIALLY CLINICIAN IS ATTEMPTING TO MATCH A PATIENT WITH DRUG. AND HOW DO WE DO THAT? WHAT WE ARE ATTEMPTING TO DO IS TO MATCH THE MECHANISM BY WHICH THE DRUG ACTS WITH THE MECHANISM OF PAIN. THE MECHANISM BASED TREATMENT OF PAIN, HAS THE UNDERLYING HYPOTHESIS THAT THE CLINICAL PHENOTYPE THE PRESENTATION OF THE PAIN, THE FLAVOR OF THE PAIN REFLECTS THE UNDERLYING MECHANISM, AND IF WE CAN THEN GO BACKWARDS AND SAY WELL, WE CAN TWO FROM PHENOTYPE TO MECHANISM, MECHANISM TO DRUG AND FIND THE PERFECT MATCH FOR THE PATIENT. NOW, OF COURSE YOU NEED TO SUSPEND DISBELIEF TEMPORARY TO MENTION THAT THIS IS AS SIMPLE AS THAT, MULTIPLE MECHANISMS THAT UNDERSTOOD LIE PHENOTYPE AND MULTIPLE MECHANISMS ADS WELL. BUT IN THE PERFECT WORLD THAT WOULD BE WHAT ONE WOULD DO WITH QUANTITATIVE TESTING, MATCH THE PATIENT WITH THE DRUG. ALSO UNDERLYING THIS IS THE NOTION PAIN MECHANISM TRANSCENDS THE DISEASE ITSELF. MORE IMPORTANT THAN THE DISEASE DIABETIC PERIPHERAL NEUROPATHY, POST HER PETTIC NEUROALGIA IS THE MECHANISM UNDERLYING THE PAIN. SPARSE THIS IS CONCERNED, I REMAIN AGNOSTIC BUT I WANT TO TAKE YOU THROUGH THE ARGUMENT BY USING A VERY OLD MICROGRAPH OF A PERIPHERAL NERVE IN THE MICROGRAPH OF PERIPHERAL NERVE WHICH THERE ARE -- IF YOU LOOK OVER THERE A PATIENT WHO HAS A TOTALLY NORMAL PERIPHERAL NERVE, HERE YOU HAVE NEUROPATHY, YOU CAN SEE LOSS OF FIBERS WITH LARGE AND SMALL, A LITTLE MORE, TOTAL DEVASTATION. EVEN THE NON-AFICIONADO CAN SEE THIS IS NOT THE SAME AS THAT. THESE ARE PATIENTS WITH VARYING GRADE OF NEUROPATHY AND YOU CAN HAVE PAINFUL DIABETIC NEUROPATHY OR IN THE SETTING OF DIABETES IN THIS SETTING AND THAT AND THAT AND THAT. AND ONE WOULD BE VERY HARD PRESSED TO IMAGINE THESE PATIENTS WHO OLE I CREATE THE ANALOGY, ALL HAD PAIN WOULD HAVE THE SAME MECHANISM UNDERLYING THEIR PAIN. MAKING THE CASE THAT PERHAPS THE ARGUMENT DOES HOLD SOME WATER THAT MECHANISM IS AT LEAST AS IMPORTANT AS DISEASE AND PERHAPS IN SOME PATIENTS MORE IMPORTANT THAN DISEASE. I WANT TO TALK NOW ABOUT LABORATORY BASED QUANTITATIVE SENSORY TESTING. THIS IS REGARDED AS THE GOLD STANDARD. THE GROUP THAT'S DONE THE BEST BODY OF WORK IS THE GERMAN RESEARCH NETWORK WHICH HAVE OVER THE PAST 15 YEARS, ACCUMULATED A LARGE NUMBER OF PATIENTS STANDARDIZE THE TESTS AND HAVE REALLY DONE THIS I THINK AS BEST IT COULD POSSIBLY BE DONE. AND THEY HAVE A INVESTIGATOR OF TESTS THAT ARE PART OF THEIR REPERTOIRE, THERMAL DETECTION, COLD AND HOT PAIN, MECHANICAL DETECTION, MECHANICAL PAIN SENSITIVITY, STIMULUS RESPONSE FUNCTIONS AND PANNES MISSION, TEMPORAL SUMMATION. EXTENSIVE BATTERY OF TESTS BEAUTIFULLY STANDARDIZED IN ORDER TO CARRY OUT THIS IS PART OF THE DFNS GROUP YOU SPEND A DAY OR TWO IN MAN HEIM TRAINED BY RALPH AND THE TEST ITSELF LASTS ROUGHLY TWO HOURS. AND THE EQUIPMENT IS 20 TO $25,000. AS A RESULT OF THIS WORK PUBLISHED IN EXTENSIVE BODY OF WORK THEY HAVE ADOPTED A CLUSTER APPROACH AND MOST RECENTLY DIVIDED THEIR PATIENT DATA SET AND AGAIN, THIS NOTION OF PAIN PHENOTYPE TRANSCENDS DISEASE DIVIDED TO THREE CLUSTERS, CLUSTER ONE THE MOST PREVALENT SENSORY LOSS CLUSTER. CLUSTER 2 NEXT PREF LEEPS IS THERMAL HYPERALGESIA AND CLUSTER 3, MECHANICAL HYPERALGESIA. DOES THIS NOTION ACTUALLY WORK? AND THE POSTER CHILD FOR THIS NOTION WORKING IS A STUDY CARRIED OUT BY THE DANISH GROUP LED MY CHARLES JENSON LOOKING AT NON-SELECTED SODIUM CHANNEL BLOCKER, AND THEY SHOWED THAT IN PATIENTS WHO HAD WHAT THEY CALL D NOSEYS ACCEPTTOR WHICH GO BACK ONE SLIDE, SORRY. I'M MOVING FORWARD. WHICH -- TO SOME EXTENT CORRELATES WITH THE THERMAL CLUSTER 2 AND CLUSTER 3, SO THERE ARE NON-IRRITABLE NOCICEPTOR GROUP DIDN'T RESPOND WELL TO OXCARBAZOPENI THE NOCICEPTOR HYPE ACTIVITY RESPONDING TO HER MALL AND MECHANICAL STIMULI RESPONDED WELL. OXCARBAZAPEME WAS A DRUG I FORGET WHO THE COMPANY WAS, PERHAPS NOVARTIS IN MULTI-CENTER CLINICAL TRIALS WHICH FAILED THIS SUGGESTS IF THE DRUG WAS USED THE SODIUM CHANNEL BLOCKER WAS USED IN EARLY PATIENTS WHO HAD IRRITABLE NOCICEPTOR, THE DRUGS COULD HAVE BEEN -- THE TRIALS WOULD HAVE BEEN SUSCEPTIBLE. THIS IS THE POSTER CHILD, NOT EVERY TRIAL HAS SHOWN THIS MECHANISM BASED APPROACH DOES WORK. AS I MENTIONED, TWO DAYS IN IN MAN HEIM TESTS THAT LAST TWO HOURS, EQUIPMENT THAT LASTS -- COSTS $25,000, ONCE IN A MEETING WITH PFIZER THAT CLIFF FORD WOLF WAS THERE AS WELSHING WE DISCUSSED THE POSSIBILITY THAT THERE MIGHT BE ANOTHER WAY OF DOING THAT TO BRING THIS TWO HOUR PROTOCOL TO THE MASSES. SO I DEVELOPED A PROTOCOL THAT THIS COULD BE DONE BEDSIDE BUT IT WAS IMPORTANT THIS WAS DONE WITH THE PSYCHOPHYSICAL PRINCIPLES THAT AS I MENTION DATE BACK TO 1800s AND WILL YOU SEE THE ELEMENTS OF PSYCHOPHYSICS BY FETNA, REGARDED AS THE FATHER OF PSYCHOPHYSICAL TESTING AND PRINCIPLES AND THIS IS ALSO ONE OF THE CLASSIC SIGNAL DETECTION THEORY IN PSYCHOPHYSICS WHICH HAS IMPLICATIONS NOT JUST WITH PHYSIOLOGY AND PAIN BUT ALSO WITH RADAR, VARIETY OF WAYS OF DETECTING SIGNAL FROM NOISE. SO TO DEVELOP A PROTOCOL CONSISTENT WITH THESE PRINCIPLES, BUT EXPENSIVE TRAINING AND WOULD BE SUITABLE FOR CLINICAL TRIALS, MULTI-CENTER CLINICAL TRIALS WHICH THESE DAYS ARE CONDUCTED BY INDIVIDUALS WHOP DO NOT HAVE QUANTITATIVE SENSORY LABORATORIES AND ARE NOT EVEN PAIN EXPERTS. THE AIM WAS SIMILAR IN LAB TO HAVE RIGOROUS CONTROL OF THE ENVIRONMENT, STANDARDIZE AND CALIBRATE STIMULI, FIXED DELIVERY PARADIGM AND HAVE THAT STANDARDIZED RESPONSE BASED ON PRE-SPECIFIED INSTRUCTIONS SO TO DO EVERYTHING THAT IS DONE IN THE LABORATORY BUT HAVE THE EQUIPMENT COSTING SUB SANNIALLY LESS. SO WOULD IT DEVELOP, A GROUP OF TEST CASE WHICH YOU SEE OVER HERE, ONE METAL RODS AND THERMOMETER TAP WATER CONTAINERS, TO HOLD ICE AND BOILING WATER AND A SCALE. THIS IS QUANTITATIVE SENSORY TESTING EQUIPMENT AND IT LOOKS LIKE THIS. IF YOU THINK THIS IS THE THING YOU MIGHT FIND IN YOUR GRANDMOTHER'S HOUSE, IT IS EXACTLY THAT. EVERYTHING CAN BE PURCHASED AT HOME DEPOT, THE KETTLE I DON'T THINK YOUR GRANDMOTHER WOULD WANT IN HER HOUSE. THIS IS THE KIT. WE ARE CAPABLE WITH THIS TEST OF TESTING SENSORY THRESHOLDS, STATIC MECHANICAL ALLODYNIA, DYNAMIC MECHANICAL ALLODYNIA, HYPERALGESIA, TEMPORAL SUMMATION AND VARIETY OF THERMAL TESTS WHICH IS JUST ABOUT EVERYTHING THAT CAN BE DONE BY THE GERMAN PROTOCOL. HERE ARE, I'M JUST GOING TO NOW TALK QUICKLY THROUGH THIS. THERE ARE GENERAL PRINCIPLES THAT WHEN WE HAVE DONE THIS IN MULTI-CENTER TRIALS, THIS IS THE TRAINING RESEARCH COORDINATORS GET, TO EMPHASIZE RESEVERAL COORDINATORS NOT TRAINED IN LABORATORY QST BUT ENVIRONMENT, COMFORTABLE TEMPERATURE, 30 SECONDS IN BETWEEN TESTS. I WILL DO THIS FROM THE TOP. THIS IS THE SENSORY THRESHOLD DETERMINATION USING BRONFREI HAIRS, THE TESTING READ THIS IS IN STANDARDIZED WAY TO SUBJECT, I WILL NOW PLOT FILAMENTS OF VARIOUS THICKNESS TO THE AREA OF MAXIMAL PAIN. I WON'T READ THE WHOLE THING BUT YOU GET THE SENSE THIS IS CAREFULLY STRUCTURED, SAME WITH STATIC MECHANICAL ALLODYNIA. THERE'S A VIDEO -- EXCUSE ME. THERE IS A VIDEO OUT COULD YOU PRESS, BEFORE YOU ABLE TO DO THAT? IF YOU CAN TOUCH THE FOOT. THERE YOU GO. YOU CAN HIT THE ARROW. CAN YOU HIT THE ARROW? IF YOU CAN. NOT THE END OF THE WORLD. I CAN DO IT. GREAT. FROM I WAS SAYING IS DIFFICULT TO DO. SO AGAIN, INSTRUCTIONS, THIS IS FROM A KIT THAT IN MULTI-CENTER TRIALS THE COORDINATORS HAVE GIVEN SO IT'S VERY CLEAR EXACTLY THOUSAND DO IT. TEN SECONDS PRESSURE SUFFICIENT TO PUPPINGTURE THE SKIN, IT'S CLEAR EXACTLY HOW TO DO IT. ONCE AGAIN, THE TESTER READINGS THIS TO THE PARTICIPANT AND AT THE END RATING THE PAIN PRODUCED BY THE PLASTIC PRESSURE BUT THE PAIN OR THE PRESSURE, NOT GIVING YOU THE WHOLE APPROACH BUT THIS IS HOW IT IS DONE. DOES THIS WORK? IN THE PFIZER TRIAL LOOKED AT FOUR GROUPS, YOU CAN SIGH ACROSS THE GROUPS PATIENTS HAVE A VARIETY OF DISEASES, HIV DBM SEEN AT THE BOTTOM AND YOU CAN SEE I WON'T GO THROUGH DETAILS BUT THREE PATIENT POPULATIONS, AND YOU CAN SEE THE PHENOTYPE IS NOT DRASTICALLY DIFFERENT ACROSS THE PATIENT POPULATION. REINFORCING NOTION THE PAIN PHENOTYPE IS MORE MECHANISM DRIVEN THAN DISEASE DRIVEN. CAN THIS BE USED AS A RESPONSE PREDICTOR? MY POSTER CHILD IS HIV NEUROPATHY TRIAL, A NEGATIVE TRIAL, HOWEVER, IN THOSE PATIENTS WHO HAD HYPERALGIERSIA WHO SCORED GREATER THAN 8 IN A NEGATIVE TRIAL ADS YOU SEE AT THE BOTTOM 2.24 GREAT IMPROVEMENT COMPARED TO PLACEBO. SO IF IN THIS TRIAL THEY ONLY INCLUDE PATIENTS WHO HAD QUOTE UNQUOTE IRRITABLE NOCICEPTOR THEY WOULD HAVE BEEN, IT WOULD HAVE BEEN POSITIVE TRIAL. AND IN THE OTHER MULTI-CENTER TRIAL, IN THE -- THESE MULTI- CENTER TRIALS THINGS ALSO A PATIENT POPULATION TWO OF THE THREE NEGATIVE TRIALS IN PATIENT POPULATION THAT HAD IMPROVEMENT IN PLACEBO OF 1.34 STATISTICALLY SIGNIFICANT, THE -- WAS FAILING WITH THAT GROUP THEN IN A SECOND ANALYSIS CONFIRMATORY USING THE SAME CRITERIA, THERE WAS -- THIS WAS A SPINAL CORD INJURY, STUDY, AGAIN, NEGATIVE STUDY, IMPROVEMENT, STATISTICALLY SIGNIFICANT IMPROVEMENT IN THOSE WITH THE PHENOTYPE AND THOSE THAT DID NOT. WE TOGETHER WITH ROB EDWARDS KRISTEN HAVE DONE VALIDATION STUDIES, YOU CAN SEE HERE, LOOKING AT REPRODUCIBILITY, THERE IS FOR A PHYSIOLOGICAL TEST PRETTY GOOD REPRODUCIBILITY BETWEEN TWO VISITS SPACED DAYS APART. WEAK CORRELATIONS WITH HEAT AND THIS IS ALSO SEEN IN THE LABORATORY BASED TESTING AND WE ARE TRYING TO REFINE AND IMPROVE THIS BUT THIS IS TWO POINTS, ONE NOT BAD FOR PHYSIOLOGICAL TEST, AND MUCH BETTER THAN SIMULTANEOUSLY CONDUCTED MPSI SO A SYMPTOM SCORE. I THINK IT'S IMPORTANT TO NOTE, I CANNOT TALK ABOUT PAIN ASSESS MENT TOOLS WITHOUT BEAR IN MIND THE POINT MADE BY CHRIS YESTERDAY ABOUT HOW PATIENTS DO NOT FEEL THESE PAIN ASSESSMENT TOOLS ASSESS THEIR PAIN EXPERIENCE, NEVERTHELESS WE SEE THEY EVOKE PAIN HAVING HAVING GOOD EMPHASIS ON HOWEVER NPSI H POSSIBLE THIS IS THE COMPARISON BETWEEN LABORATORY BASED QSD SO CALLED GOLD STANDARD SO CALLED I'LL ELABORATE ON THE LAST SLIDE, YOU CAN SEE REASONABLE CONCORDANCE AS WELL THE WEAKEST IS BETWEEN DYNAMIC MECHANICAL WHICH SHOWS BECAUSE THERE'S NOT PRECISE TEST, PERFECTION IN TERMS OF SAYING THIS EXACTLY TESTS AND YOU SEE WHAT I MEAN WHEN I DO THAT, WHEN I TALK ABOUT THAT, IN A SECOND, BUT THIS IS THE WAY IT'S DONE IT'S A VERY DIFFERENT TEST BUT THERE IS REASONABLE CONCORDANCE. WE LOOK AT THE RELATIONSHIP BETWEEN THE MPSI AND TESTING TO LOOK AT INTERNAL VALIDITY. LET ME TAKE YOU THROUGH THIS BRIEFLY. HERE YOU LOOK AT PAIN PROVOKED ON MPSI AND YOU LOOK AT COLD HYPERALGESIA AND YOU CAN SEE LOOKING USING THAT SCALE, PRE-TY GOOD CORRELATIONS. SAME THING WITH PAIN PROVOKED AGGRESSION AND DYNAMIC ALLODYNIA. AND PAIN PROVOKED BY PRESSURE AND STATIC ALLODYNIA. WE ACKNOWLEDGE LOOKING AT A QUESTIONNAIRE PATIENT'S DAILY EXPERIENCE OF PAIN VERSUS A MOMENT IN TIME IN CONCORDANCE AND OUR CONCLUSION WAS ONE THIS VALIDATES APPROACH AND WHO YOU IMMEDIATE TO DO BOTH TO CAPTURE THE ENTIRE PAIN PHENOTYPE. WE JUST LOOKED AT THAT AS A WAY OF ASSESSING INTERNAL VALIDITY A PAPER PUBLISHED A MONTH OR TWO AGO FROM THE GERMAN GROUP, PAIN MECHANISM AND LOOKED AT THE LEADS AND NEUROPATH iIC PAIN SCALE AND CAME TO THE SAME CONCLUSION, BOTH ARE COMPLIMENTARY FOR PAIN ASSESSMENT. ATTEMPT TO CAPTURE THE PAIN EXPERIENCE. I WANT TO AS I CLOSE TALK ABOUT THE CONTRAST BETWEEN THE TESTS. FIRST OF ALL OBVIOUSLY WITH THE EXCEPTION OF -- WHICH COSTS $120 LESS THAN $20 FOR THE WHOLE KIT. STATIC STIMULI VERSUS DYNAMIC STIMULI, WHAT TO I MEAN? I TOLD YOU ABOUT THAT METHOD LIMITS ONE DEGREE PER SECOND, RAMP INCREASING VERSUS A STATIC STIMULUS YOU PLACE COLD ROD OR HOT ROD ON THE PATIENTS PAINFUL AREA AND YOU SAY HOW PAINFUL IS THIS OR DO YOU FEEL IT IS PAIN, ONE CAN ARGUE THAT PERHAPS THIS IS BETTER WHAT DO I MEAN THAT BY THAT? METHOD OF LIMITS JUST SAY YOU HAVE THE PATIENT WHO IS I DON'T KNOW THE -- DO I FEEL IT TO BE OR NOT TO BE, MAYBE I TO, MAYBE I DON'T. MEANWHILE THIS RAMP IS INCREASING AND IT'S WAY BEYOND THE THRESHOLD YOU HAVE PERHAPS AN ARGUMENT IN SUPPORT OF NOT USE METHOD OF LIMITS BUT USING METHOD OF LEVELS AND MOST PEOPLE USE LABORATORY BASED QST USE METHOD OF LIMITS. LABORATORY BASED REACTION TIME DEPENDENT QST INDEPENDENT. WE AND AGAIN THIS IS A LITTLE BIT OF ELABORATION, THEY LOOK AT THE THRESHOLD WHEN DO YOU FEEL IT, WHEREAS WE RIP THE PAIN INTENSITY, SUPERIOR, TEST DURATION WE DO THIS MANY 20 MINUTES THEY DO IT IN TWO HOURS H. CALIBRATION. CALIBRATION IS IMPORTANT. IF YOU ASK PEOPLE WHO DO LABORATORY TESTING WHEN LAST DID YOU CALIBRATE EQUIPMENT TO BE SURE THAT 15-DEGREES IS 15-DEGREES, THEY WON'T GIVE DIRECT ANSWER. MOST DON'T CALIBRATE THEIR EQUIPMENT. I SPOT IS I SPOT FOUR DEGREES IS FOUR DEGREES AN SICKLE CENTER VERSUS MULTI-CENTER. EASILY DONE IN A MULTI-CENTER TRIAL. SO CONCLUSIONS AND ROADMAP. SOME SUPPORT FOR THE PHENOTYPE TO MECHANISM HYPOTHESIS, WE TO HAVE TEST RETEST RELIABILITY, TEMPORAL STABILITY, GOOD CORRELATIONS, THE SYMPTOMS SHOWED GREATER VARIABILITY. THAN EVOKED PAIN. I THINK THIS SUPPORTS THE NOTION TO PHENOTYPE AND OBLIGATE FOR ALL TRIALS, IT'S A WONDERFUL OPPORTUNITY FOR ACADEMIA INDUSTRY DIRECTION AND MECHANISM FOR POOLING DATA ACROSS A VARIETY OF STUDIES LOOKING AT DRUGS WHICH HAVE MULTIPLE MECHANISMS. I WENT OVER TIME. THANK YOU FOR LISTENING. [APPLAUSE] >> OUR NEXT SPEAKER HAS A REAL LONG INTRODUCTION. JUST KIDDING. NEXT SPEAKER IS DR. DAVID BOONE, A BIOMECHANICAL ENGINEER AND CURRENTLY CEO OF ORTHO CARE INTERVENTIONS IN SEATTLE. ASSOCIATE PROFESSOR OF BIOINFORMATICS AT THE HONG KONG POLYTECHNICAL POLYTECHNIC UNIVERSITY, DR. BOONE AND HIS TEAM ARE DEVELOPING WEARABLE SENSORS AND APP BASED INTERVENTIONS FOR PHYSICAL REHABILITATION AND PHARMATRON. >> THANK YOU. GOOD MORNING. I WOULD LIKE TO THANK THE ORGANIZERS FOR THE INVITATION. I CERTAINLY LEARNED A LOT ABOUT PAIN. IT MADE ME REALIZE MY ENTIRE CAREER HAS BEEN AROUND PROSTHETICS RESEARCH AND I HAVE BEEN FOCUSED ALWAYS ON COMFORT. THE USE OF A PROSTHESIS IS REALLY MODERATED BY DISCOMFORT. SO I GUESS I'M HERE FROM SLIGHTLY DIFFERENT ANGLE. I ALSO WANTED TO SAY HAPPY VALENTINE'S DAY. ESPECIALLY DEBRA WHO IS WATCHING THE WEBCAST. DISCLOSURES, I WANT TO THANK NICHD AND NIA FOR SPONSORING THE RESEARCH INTO HOW WE HAVE BEEN LOOKING AT AMBULATORY ACTIVITY AND VAR AND D. WE HAVE LOOKED OVER THE LAST 30 YEARS AT AMBULATORY ACTIVITY IN PROSTHETICS. AND MANY ASPECTS KINETICS AND KIN MA TICKS AND PRECISE EVALUATIONS OF MOTION AND COMPENSATORY MOTION WITH PROSTHESIS THAT AREN'T WORKING WELL. I WILL TALK ABOUT THE STEP. TOTAL STEP COUNTS, FROM FROM FIT BITS AND THINGS. THERE'S A LOT OF VALUE IN THE STEP. I WANT TO MEASURE TALK ABOUT THAT FIRST, FIRST IT'S MEASURABLE. WE CAN PRETTY ACCURATELY MEASURE STEPS SO YOU HAVE TO BE CAREFUL HOW YOU DO IT. IT'S DATA EFFICIENT BECAUSE IT IS A SUMMARY MEASURE, A STEP SO MANY THINGS HAPPENED FOR YOU TO DECIDE THE TAKE A STEP EMOTIONALLY, PHYSICALLY GET UP AND DO IT FOR THE MUSCLE CONTROL TO WORK, NOT TO FALL DOWN. SO IF YOU SUCCESSFULLY HAVE TAKEN STEPS, IT'S DATA EFFICIENT TO COMPACT TO SAY WE HAVE DONE THOSE THINGS. IT'S INTERPRETABLE. WHAT I MEAN IS THAT A STEP HAS A MEANING TO EVERYONE IN THIS ROOM ALREADY. IF I TALK ABOUT A SPECIFIC KIN MATTIC MEASURE, MOST IN THIS ROOM WOULD BE LOST TO WHETHER THAT WAS A VALID OR VALUABLE INDICATOR. YOU KNOW STEP MEANS YOU MOVE AT LEAST ONE STEP FROM HERE TO THERE. IT'S SCALABLE. THIS WAS THE MOST IMPORTANT THING IN OUR RESEARCH THAT DROVE US TO FOCUS ON ACCURATE STEP COUNT. A STEP OF SOMEONE IMPAIRED WITH PARKINSON DISEASE, MULTIPLE SCLEROSIS AND AMPUTATION. SOMEONE HEALTHY, ATHLETIC, A CHILD, EVERY PERSON IN THIS ROOM CAN UNDERSTAND THE STEP OF A THREE-YEAR-OLD WHO IS EXCITED VERSUS A NINE-YEAR-OLD WITH A WALKER. SO A STEP ITSELF IS SCALABLE TO DIFFERENT CONDITIONS AND DIFFERENT SOMETIMES IN LIFE. STEPS THEN TEND TO BE BROKEN DOWN INTO METRICS. HERE VERY COMMON METRIC USE SUBSIDIZED, ACTUALLY PROBABLY ONE OF THE LEAST SENSITIVE TO CHANGE. BUT TOTAL COUNTS CAME OUT OF MED METERS TO START WITH AND HAY GAVE YOU TOTAL COUNT. SO THERE'S A LOT OF RELYING ON HISTORY FOR THAT. THE SIMPLE MESSAGE IS MOBILITY TURNS OUT IS INVERSELY PROPORTIONATE TO PAIN. THAT'S NOT JUST LIMITED TO MUSCULOSKELETAL PAIN WHICH IS CERTAINLY THE FOCUS OF MY RESEARCH, BUT ALSO THINGS LIKE MIGRAINE OR ANY OTHER EXPERIENCE OF PAIN THAT KEEPS YOU FROM WANTING TO MOVE. MOBILITY ITSELF IS REALLY ESSENTIAL ELEMENT OF INTERACTION WITH INDIVIDUAL'S ENVIRONMENT SO THAT IS AN IMPORTANT THING. BECAUSE OF THAT, WE LONG ADVOCATED FOR MOBILITY AS A PRIMARY SECONDARY OUTCOME. THE TRIAL Z BECAUSE IF YOU CAN INTERACT WITH YOUR ENVIRONMENT, THAT OPENS UP MANY OTHER OF THE OUTCOME BOLES YOU MIGHT WANT FOR MANY DIFFERENT CONDITIONS. I THINK UNDER 21ST CENTURY EXCUSER ACT AND ABILITY TO HAVE NEW CLINICAL OUTCOMES ASSESSMENT SOME OF THIS BEING RECOGNIZED AND BROUGHT IN. TO PLAY IN LOOKING AT INTERVENTIONS. THE TOPIC OF THIS SECTION IS LOOKING AT TRIALS SO WHEN I GRABBED A FEW FDA CURRENT TRIALS THAT I CAN TALK ABOUT, I HAVE PERMISSION TO MENTION THESE ARE ONGOING AND USING STEP COUNT PRIMARY SECONDARY MEASURE. THESE ARE ALL PROPRIETARY FOR THE PHARMA COMPANIES, I CAN'T GO INTO DETAIL BUT WHAT THEY ARE FINDING OR WHATEVER. I WANTED TO MENTION THERE IS TRACTION NOW. FOR USING AN OUTCOME. EVEN A PRIMARY OUTCOME. I ALSO WANTED TO MENTION THAT I -- BECAUSE I COULDN'T TALK A ABOUT THESE I DID DIG INTO THE CURRENT LITERATURE ABOUT WHAT WAS -- THIS IS AN OLDER SESSION OF MY PRESENTATION BUT I WILL GO THROUGH IT QUICKLY. IF WE LOOK AT MUSCULOSKELETAL PAIN, THERE IS -- THIS GROUP LOOKED AT HIP INJURIES. SHOW PAIN DIDN'T INFLUENCE WALKING, THAT'S NOT A REALLY STRIKING FINDING BUT IT IS NICE TO SHOW THAT THE MEASUREMENT OF ACCURATE WALKING IS REFLECTED AND CORRELATES WITH PAIN, THE AMOUNT OF PAIN THE PEOPLE THAT HAD HIP INJURIES REPORTED. LARGE STUDY OF BAREIA RICK SURGERY PAIN IS A PREDICTOR WHEN YOUR POSTOP SIFT LEVEL SO I WAS LOOKING A SLIGHTLY DIFFERENT WAY. THAT PAIN ITSELF AND AMOUNT OF PAIN YOU HAD PRE- AND POST SURGICAL, WOULD BE PREDICTOR FOR HOW MUCH YOU WOULD, IF YOU ARE ACCURATELY MEASURING HOW MUCH YOU ARE WALKING THAT IS INDICATION INVERSELY OF PAIN. FINALLY, WE JUST RECENTLY LOOKING AT COPD POPULATION UP IN TORONTO. INCLUDED PAIN LED TO LOWER PHYSICAL ACTIVITY. GOING ON QUICKLY THROUGH SOME OTHER STUDIES THAT I THINK WILL QUITE INTERESTING. THIS IS FOR SHARK TOOTH WHICH HAS PAIN COMPONENT ASSOCIATED WITH IT THOUGH IT'S NEUROPATHY. TO ME THIS IS QUITE INTERESTING BECAUSE THIS GROUP DECIDED TO -- PAST TRIALS OF DRUGS FOR CMT NOT SHOWN POSITIVE RESULTS. THEY DECIDED OUTCOME MEASURES. BEING USED. IN THIS CASE THIS ACTIVITY MONITOR STEP WATCH AND 12 MONTH LONGITUDINAL STUDY DID SHOW THAT THE AS A DISEASE PROGRESS CHANGE IN PHYSICAL ACTIVITY. DASHEENS MUSCULAR DISROOFIE LOOK AT ADOLESCENT BOYS, DIFFERENT POPULATION, SO REALLY HIGH CORRELATIONS IN ACTIVITY BIOMARKERS AS DISEASE PROGRESSED. NOW, THIS ISN'T DIRECTLY RELATED TO PAIN THOUGH AGAIN PAIN IS A COMPONENT OF DECREASING ACTIVITY. IN DUE SHEN. PARKINSON DISEASE WHICH WAS MENTIONED EARLIER, VERY HARD ACTIVITY TO MEASURE. SO ONE OF THE THINGS OUR PREVIOUS FUNDED RESEARCH WAS ABOUT, ESPECIALLY NIH FUNDING, LOOKING AT IMPAIRED GATE, HOW DO YOU QUANTIFY A STEP FROM SOMEONE WHO HAS SUCH A SHAPE TRAJECTORY. IN THIS CASE CAFF GNAW FOUND A WHOLE SLEW OF NORMAL OUTCOME MEASURES, INSIGNIFICANT TO SHOW CHANGE AFTER A YEAR PARKINSON DISEASE BUT IN FACT VERY HIGH EFFECT SIZE, LARGE EFFECT SIZE, LOOKING AT THE STEP ACTIVITY. NOW IN MY TITLE I TALK ABOUT DOSE RESPONSE, THIS GETS INTO THE CHALLENGES WE HAVE. MEASURING STEP ACTIVITY. FROM MS.FIRST OF ALL ONE OF THE THINGS WE LEARN WITH STEP ACTIVITY IS ACTIVITY PREDOMINATE. WHERE DO YOU GO TO SCHOOL, IF YOU WORK WHAT KIND OF PHONE YOU HAVE, WHETHER OR NOT YOU I PLEA, WHETHER OR NOT YOU HAVE A PET, A DOG IS A HUGE INDICATOR OF STEP ACTIVITY. THESE PREDOMINATE AND SET A BASELINE. CHANGES IN PAIN, CHANGES IN OTHER INTERVENTIONS CAN EFFECT THAT BASELINE. AS LONG Z YOU OARLOCK AT IT LONG ENOUGH SO AGAIN, LOOKING AT FREE ROAMING DATA IN THE COMMUNITY FOR LONG PERIODS OF TIME ARE VERY IMPORTANT SINGLE EPISODE IN A CLINIC, YOU'RE NOT GOING TO MEASURE A DIFFERENCE HERE, IN SOMEBODY'S ABILITY TO WALK. AS LONG AS YOU HAVE AT LEAST A FULL WEEK, WE TEND TO RECOMMEND NINE TO 14 DAYS. YOU GET OUT OF BASELINE, THIS WILL TAKE INTO ODD DAY WHERE YOU ARE NOT FEELING WELL AND YOU CAN FILTER THOSE OUT. WHAT I MEAN BY DOSE RESPONSE IS VERY CLEAR THAT PATIENTS SELF-TITRATE THEIR GATE ACTIVITY BASED ON DISCOMFORT AND ABILITY. IF YOUR -- ITs A A DIFFICULT HINGE TO GET AT PAIN WITH SOMEONE BASED ON ACTIVITY BECAUSE THEY ARE GOING TO DO LESS. SO THAT'S AN INDICATOR OF PAIN BUT THEN THEY'LL REPORT LESS PAIN BECAUSE THEY HAVE DONE LESS. SO SO BUT YOU HAVE TO CONSIDER THAT THE MEASUREMENT OF ACTIVITY IS INDICATOR NOT NECESSARILY HOW MUCH PAIN THEY HAVE BECAUSE THEY PROBABLY REDUCE PAIN LEVEL BY NOT WALKING, BUT MAYBE INDICATOR THAT YOU SHOULD GO LOOK AT ARE THEY REDUCING ACTIVITY. FOR US IT'S IMPORTANT TO LOOK AT ACTIVITY OCCURS THROUGHOUT THE DAY. SO HERE IS ONE DAY FROM MIDNIGHT TO MIDNIGHT, SLEEPING, THEY HAD SOME ACTIVITY, FIRST THING IN THE MORNING SOME EXERCISE ACTIVITY, THERE'S OFFICE WORK. BY LOOKING CLOSELY AT HISTOGRAM OF ACTIVTY OVER TIME YOU HAVE A RICHER EVALUATION SOMEBODY MODULATING PAIN -- MODERATING PAIN BY REDUCING ACTIVITY. ANOTHER IMPORTANT CONFOUNDER IS DEPRESSION. SO AS NOTED, DEPRESSION OFFICE CHANGES AND SUPERBOWL WE SAW THAT EVERY YEAR, PEOPLE WITH NO ACTIVITY FOR FOUR HOURS. HERE IS A CASE STUDY THATD DOES SALT LAKE CITY REPORTED ON, IING THEY WERE LOOKING AT POST AMPUTATION PAIN. THIS IS WEEKS POST AMPUTATION WITH PROSTHESIS. AND LOOKING AT THE WALKING ACTIVITY. THEY FOUND A HUGE DROP IN THE SIX WEEK OF THE TREATMENT OF THIS PATIENT. THE CLINIC TEAM MET AND WITH THE PATIENT THEY FOUND THE PATIENT WAS DEPRESSED. SO FIRST TIME THESE REHAB PHYSICIANS BECAME FAMILIAR WITH THE FACT THIS PATIENT HAD THIS BUILDING DEPRESSION WAS FROM THEIR ACTIVITY LEVEL. THAT'S CONFOUNDER IN A WAY THE TEE PRESENTATION THAT CAUSE HEM TO DROP THIS, THE GOOD NEWS IS IT DID ALTER THE TREATMENT AND ALERTED MENTAL HEALTH SERVICE SALT LAKE DA, THEY STARTED TREATMENT AND THEN YOU CAN SEE FROM THAT POINT RETURN TO THE LEVEL OF FUNCTION THE PAIN HAD BEFORE. FINALLY, ASSAYS OF ACTIVITY ARE NOT ALL EQUAL. SO EVERYONE HAS HAIR SOAP BOX. MINE IS ABOUT THIS VALIDITY OF STEP -- IT'S DANGER OF WORKING TOO LONG IN ANY ONE THING AND YOU GET OBSESSIVE ABOUT IT. STEP COUNTERS ARE NOT EQUAL. WE NEED TO CONSIDER HOW ACTIVITY OCCURS, THIS IS ACTUALLY WORK PART OF IT IS PATIENTS DO UNIT WALK MORE THAN JUST VAGUE LINE. IF YOU LOOK AT ACTIVITY COUNTERS FOR CONSUMER BASE THEY ARE TYPICALLY FOR EXERCISE ACTIVITY, IF YOU RUN ON A TREADMILL THAT'S RUNNING IN A STRAIGHT LINE. AND IT'S TYPICALLY A CONSTANT SPEED. THE GAIN OF DAILY LIVING INVOLVES INITIATION OF GATE. ACCELERATION, DECELERATION, MANEUVERING, THINGS SO YOU ARE RUNNING AROUND ALL THE TIME TRYING TO STOP. ANOTHER WAY TO LOOK AT THIS IS THAT GATE ACTIVITY WALKING ACTIVITY IS REALLY OCCURS IN SHORT INTERVALS. SO THE MOST COMMON BOUTS, THIS IS NUMBER OF STEPS TAKEN IN THE ROOM VERTICAL ACCESS IS THE FREQUENCY. SO HOW OFTEN DID YOU TAKE THOSE STEPS? TURNS OUT FOUR STEPS IS THE MOST COMMON WAY YOU WALK. YOU START YOU TAKE FOUR STEPS AND THEN STOP. THINK ABOUT THAT, AT HOME, IN THE KITCHEN, REFRIGERATOR AND YOU STOP. YOU WALK TO THE SINK TO THE TABLE AND YOU STOP. IN YOUR OFFICE YOU GO TO THE PRINTER TO THE DESK AND ROW STOP. CONTINUOUS WALKING IS NOT A GREAT BAY TO VALIDATE. IN TERMS OF STEP COUNTING. WE LOOK AT 75% FOR ONLY 40 STEPS, HARDLY GET ME OUT OF THE ROOM. ARE ENVIRONMENT WHETHER OFFICE ENVIRONMENT, HOME ENVIRONMENT, IS TOKING TO BE THAT KIND OF TIME. WE ARE SPENDING 75% OF OUR TIME DOING THOSE SORTS OF ACTIVITIES. AND REALLY WE LOOK AT MORE LIKE EXERCISE ACTIVITY, MIGHT CALL THAT EXERCISE. WE ARE TALKING FRACTION OF A PERCENT OF OUR TIME. DURING THE DAY. SO THIS IS WHY STEP COUNTERS THAT YOU MIGHT GO OUT AND BUY CONSUMER LEVEL ARE NOT ACCURATE. ANOTHER THING DETERMINED NOT MOVING STRAIGHT AHEAD. TYPICALLY A PERSON TURNS EVERY FIFTH STEP. SO NOT STRAIGHT AHEAD WE NEED TO THINK LATERAL MOTION WITHIN THAT STEP AS WELL. FROM THE ENGINEERING SAND POINT, DESIGNING A SENSOR, THIS IS REALLY IMPORTANT. THIS IS TRACING 2017, A LOT OF EVIDENCE COMING OUT ABOUT THIS, THAT WAS SOAP BOX PART. IF I'M LOOKING AT A POPULATION THAT I'M RECORDING PHYSICAL ACTIVITY WITH SOMETHING THAT'S A FIT BIT MAYBE 30% ACCURATE, THAT INTRODUCING A LOT OF ERROR. UNFORTUNATELY IS NOT JUST ONLY 30% ACCURATE BUT ALWAYS UNDERCOUNTING STEPS. SO WE REALLY ARE NOT GETTING THE ACCURACY. THE POINT LUCA MADE BACK IS VALID, WE ARE LOOKING AT A PATIENT USING THEIR ORNATE VICE OVER TIME, THERE'S A SEQUENCE HERE HA YOU CAN GET INFORMATION ABOUT HOW THE CHANGE IS OCCURRING. BUT ANY OTHER CLINICAL ASSAY YOU ALWAYS WANT TO TRY TO GET ACCURACY, RELIABILITY, TREATABILITY. PART OF THIS IS BECAUSE OF SPEED. SO IF WE LOOK AT PERSONS WHO HAVE ANY KIND OF IMPAIRMENT INCLUDING PAIN, THEIR SPEED DECREASES. THE MORE SPRITELY YOU WALK YOU CAN ENVISION THIS, IN THE STEP, YOU ARE FEELING HEALTHY AND BOUNCING ALONG, AS SPEED DECREASES THIS IS WHERE DIFFERENT TYPES OF SENSORS TEND TO FALL DOWN. SO AGAIN, ATTUNED SORT OF VERY IN MOST CASES VERY DELIBERATELY FOR EXERCISE. HIGH VELOCITY, REPEATABILITY STRAIGHT LINE. WE LOOK HERE, THIS WAS A VERY INTERESTING STUDY WHERE THEY TOOK THEY MOUNTED A -- THE LITTLE CAMERA RYING TO THINK OF THE TRADE NAME. GO PRO NOT GO P -- A GPRO THAT POINTED DOWN AT YOUR FEET AND THEN THEY HAD ALL OTHER SUBJECTS GO OUT AND THEY RECORDED THEIR ACTIVITIES OF DAILY LIVING. ED FROM SO THEY WENT OUT INTO THE FIELD. SO THIS TO ME HAS THE BEST ECOLOGICAL VALIDITY BECAUSE THE TESTING WAS SCORED AFTERWARDS BY LOOKING AT DID THE FOOT TAKE A STEP. VISUALLY THEY CAN SEE EVERY STEP EVERY SUBJECT TOOK AND AGAIN YOU SEE UNDERCOUNTING, OVERCOUNTING, VARIABILITY. SO TO ME IMPORTANCE OF ASSESSING WHETHER OR NOT ACTIVITY IS AN ASSAY HA CAN BE USED FOR PAIN OR ANY OTHER TREATMENT, IMPORTANT TO HAVE THAT ACCURACY. SO THIS SHOWS HOW THE VIDEO IS POINTED DOWN ON THE SUBJECTS. I WOULD LIKE TO MENTION DR. TERRY CHO WHO PROBABLY SHOULD BE MENTIONED IN THIS IS MY COLLEAGUE THAT WORKS IN THIS AREA THE MOST. IF YOU ARE INTERESTED FURTHER CONTACT HER. THE STEP WATCH WE DEVELOP UNDER NIH FUNDING IS FDA CLASS 2 DEVICE WHICH IS SIGNIFICANT FOR A LOT OF THESE TRIALS AS WELL. THIS IS NOT A CONSUMER DEVICE, IT'S A MEDICAL DEVICE. THERE ARE OVER 400 PEER REVIEWED ORIGINAL RESEARCH ARTICLES NOW USING THAT. BECAUSE OF IT. ALSO POINT OUT TO THEIR CREDIT, FIT BIT IS ONE OF OUR CUSTOMERS WHICH USES STEP WATCH AS CRITERION MEASURE FOR THEIR OWN DEVELOPMENT. HOTCH. I PUT ALL THE DETAILED REFERENCES INTO THE PACKAGE. THANK YOU. [APPLAUSE] >> THANK YOU. >> VERY INTERESTING. OUR NEXT SPEAKER IS DR. DENNIS TURK. DENNIS IS JOHN AND EMMA PROFESSOR OF ANESTHESIOLOGY AND PAIN RESEARCH AND DIRECTOR OF CENTER FOR PAIN RESEARCH ON IMPACT MEASUREMENT AND EFFECTIVENESS AT THE UNIVERSITY OF WASHINGTON, EDITOR AND CHIEF OF CLINICAL JOURNAL OF PAIN, VERY WELL PUBLISHED VERY WELL KNOWN, VERY SIGNIFICANT CONTRIBUTOR IN THE PAIN FIELD EVIDENCED BID THE FACT HE'S WON THE LEBOCK SKIN AWARD FOR CAREER CONTRIBUTION FROM THE AMERICAN ACADEMY OF PAIN MEDICINE, THE AWARD FOR CLINICAL RESEARCH FROM THE AMERICAN PAIN SOCIETY AND ALSO THE JOHN AND EMMA BONIKA PUBLIC SERVICE AWARD FROM AMERICAN PAIN SOCIETY. >> THANK YOU FOR THE INTRODUCTION AND LETTING ME COME SPEAK WITH YOU. THE TROUBLE WITH INTRODUCTIONS IS MAKES YOU KNOW HOW OLD YOU ARE. MORE ACCOLADES OBVIOUSLY THE LONGER YOU HAVE BEEN AROUND. I HAVE BEEN GIVEN THE DUBIOUS TASK OF TRYING TO TAKE ALL KINDS OF THINGS YOU HAVE BEEN HEARING ABOUT METHODOLOGIES, THE AAPPROPRIATES OF DATA ACQUISITION PROCEDURE, ALL THE COMPLEX WAYS OF ASSESSING PAIN, COMPLEX WAYS OF ASSESSING SENSORY PHYSIOLOGY AND TRYING TO FIND OUT SOME CAVEATS, SOME CONCERNS, I GUESS MY REPUTATION PROCEED ME WAS A SINNIC. BUT LET ME MODIFY MY TITLE, COLLECTING COMPLEX DATA IN PAIN FOR CLINICAL TRIALS BECAUSE WHAT I'M TALKING ABOUT IS NOT JUST IN CLINICAL TRIALS BUT ALSO EPIDEMIOLOGY STUDIES WOULD BE ANY TYPE OF RESEARCH YOU'RE DOING IN AREA OF PAIN SO NOT SPECIFIC. THE USUAL ONES BUT THE ONES I WANT TO MENTION ARE NIH AND THE U.S. FDA HAS SPONSORED MY RESEARCH AND MIGHT WONDER WHY IS THAT NEED TO BE DISCLOSED? THE ASSUMPTION IS PHARMACEUTICAL INDUSTRIESES ARE BIASED AND POTENTIALLY MY PRESENTATION BUT IT'S ALSO QUITE POSSIBLE MY RELATIONSHIP WOULD BE NIH AS WELL AS RELATIONSHIP O THE FDA, ALSO COULD POTENTIALLY GET BIAS TO WHAT I WOULD SAY SO BE AWARE THAT I HAVE THOSE THINGS GOING ON. WHAT WE HAVE BEEN HEARING ABOUT ALL OVER THE LAST DAY AND TWO THIRD, DAY AND A HALF, IS ABOUT THE COMPLEXITY OF GOING FROM PATHOLOGY AND DISEASE IF YOU WILL TO SYMPTOMS, OR SIGNS, AND TEND TO HAVE FORGOTTEN SOMETHING IN BETWEEN. THAT IN BETWEEN IS WHAT WE HAVE BEEN DEALING WITH, IN THE AREA OF PAIN, FOR AS LONG AS I WORKED IN THE AREA, I HAD BLACK HAIR WHEN I STARTED. CHRIS NICELY MADE US THINK ABOUT THE PERSON TALK TO ALMOST ALL THESE LEADS I GO TO WHERE SHE DOES FORCE US TO THINK ABOUT THE END USER IF YOU WILL, END USERS (INAUDIBLE) THAT PERSON THAT HAS A PAIN PROBLEM. I WILL TRY SINCE I WAS IMPRESSED BY WHAT I HEARD YESTERDAY FROM TONYA'S DATA AND SOME OF MY OWN LITERATURE, SO I CAN UNDERSTAND WHY WE ARE HERE. THE NEXT THREE OR FOUR SLIDES DO THIS FOR ME, AND THIS IS LOOKING AT THE EFFICACY OF THE AVAILABLE TREATMENTS THAT WE CORPLY HAD TO PEOPLE WITH CHRONIC PAIN. AND NOT JUST RUN THROUGH THESE FAIRLY QUICKLY. SINGLE DRUGS HAVE MAXIMUM EFFICACY REDUCING PAIN BY 25 TO 35%. VERSUS PLACEBO. THERE'S NOT REDUCE ALL THE PAIN. SO WE TALK ABOUT INTERVENTIONS TO TRY TO IMPROVE PAIN, WE ARE NOT TRYING TO BY AND LARGE CURE PAIN, WE ARE TRYING TO REDUCE ITS. DESPITE VARIETY OF PHARMACOLOGICAL AGENTS, EFFECTIVE PAIN RELIEF AND CONVENTIONAL MEDICAL MANAGEENT ACHIEVED IN LESS THAN HALF THE PATIENTS WITH CHRONIC PAIN. SO LESS THAN HALF PATIENTS GET MY KIND OF BENEFIT AT ALL AND THOSE WHO GET IT BENEFIT IN A RELATIVELY SMALL BENEFIT COMPARED TO WHAT WE LINE LIKE TO SEE. MOST ANALGESIC DRUGS WORK, SMALL PERCENT TO THE PATIENT. THAT'S ONE REASON YOU ARE HERE, ANOTHER REASON IS WELL OKAY, AT THE END OF TREATMENT, MAYBE THERE'S OTHER KINDS OF INTERVENTIONS THAT ARE ALSO GOING TO BE GOOD. DEMONSTRATION, BY THE WAY ALL CITATIONS HERE FOR YOU TO SEE THE TREATMENT USING OUTCOMES AND META ANALYSIS LOOKING AT STATISTICAL SIGNIFICANCE FOR STRONG OPIOIDS, NON-OPIOID ANALGESICS COMPARED TO PLACEBO, PHYSIOTHERAPY, PSYCHOTHERAPY, THE END OF THE TREATMENT, THERE WASN'T ANY INDICATION OF META ANALYSIS THAT THOSE DRUGS, ANY OF THOSE DRUGS CATEGORIES ARE ANY BETTER, NO T THAT THE OTHERS ARE GREAT BUT NOT ANY BETTER. NO OPIOIDS PRODUCE CLINICALLY IMPORTANT PAIN INTENSITY (INAUDIBLE) DROP OUT RATES FOR ALL THESE PHARMACOLOGICAL -- ARE HIGH, ESPECIALLY THE ONE WITH TRIAL THE HIGHER THE DROP OUT RATE. MAYBE WE SHOULD LOOK AT INVASIVE PROCEDURES, MAYBE THEY ARE MORE EFFECTIVE THAN PHARMACOLOGICAL TREATMENT THIS IS A NICE REVIEW OF ALL THE INVASIVE KINDS OF PROCEDURES USED FOR DIFFERENT TYPES OF CHRONIC PAIN. ALL KINDS OF CHRONIC PAIN TO THE OTHER, THIS TOPIC OF PRE-CUTANEOUS INSERTIONS TO THE BODY MANIPULATION OF TISSUE ANATOMY AND ALL TREATMENTS THAT ARE ARE THERE. STANDARD KINDS OF INVASIVE APPROACHES THAT ARE USED FOR PAIN AND WHAT YOU CAN SEE FROM THIS IS THERE IS LITTLE EVIDENCE FOR THE SPECIFIC EFFICACY BEYOND SHAM OR ANY OF THE NON-INVASIVE PROCEDURES FOR CHRONIC PAIN. THINK ABOUT THAT. SO THE DRUGS AREN'T GREAT. BASE PROCEDURES WHAT WE SHOULD LOOK AT ALTERNATIVES, SO LET'S LOOK AT ACUPUNCTURE, THIS IS AGAIN META ANALYSIS, METHOD OF ACUPUNCTURE, MODERATE EFFECT BUT LOW QUALITY OF EVIDENCE, EXERSIZE, SMALL EFFECTS CHRONIC PAIN, MODERATE QUALITY LEVEL OF EVIDENCE. MASSAGE HAS NO EFFECT ON CHRONIC PAIN AND LOW EVIDENCE OF EFFICACY, SPINAL MANIPULATION SMALL TO NO EFFECT TO SMALL. THAT'S A LOW EVIDENCE STRENGTH. TAI CHI MODERATE EVIDENCE. YOGA, I CAN GO DOWN THE LIST OF OUR FAVORITES, PSYCHOLOGICAL MANIPULATIONS AND INTERDISCIPLINARY RELOCATION AND SON OF A GUN. NOT A LOT BETTER. O IF OVERALL TREATMENTS ARE MODESTLY EFFECTIVE, AND THERE'S COCHRAN REVIEWS AN META ANALYSIS, OTHERS DOWN THERE WILL, WHY IS IT -- WHY ARE WE HAVING SO MANY DIFFERENT TREATMENTS OVER SO MANY THOUSANDS OF YEARS AND STILL DON'T HAVE FAITH OUTCOME? WHAT WE HAVE BEEN TALKING ABOUT THE LAST CUPFUL O DAYS MIGHT HELP US UNDERSTAND THAT. THIS IS -- COUPLE OF DAYS MIGHT HELP UNDERSTAND THAT. SET ASIDE THE VARIABILITY, VARIABILITY IN INDIVIDUALS. THIS IS ON GENETIC VARIABILITY JEFF SHOWED USING A INBRED MOUSE STRAINS USING THREE PROCEDURES TO INDUCE THE PAIN, WHAT YOU CAN SEE THOSE DIFFERENT GROUPS STRAINS OF MICE, THIS WIDE VARIABILITY IN HOW DIFFERENT STRAINS RESPOND, GENETIC FACTORS SEEM TO BE IMPORTANT. BIG SURPRISE BUT NOT ONLY IN HUMANS, IT'S ALSO IN RODENTS, THIS IS IMPORTANT. THINK ABOUT HEALTHY INDIVIDUALS, MAYBE IT'S RODENTS WE CAN'T TRUST AND THE PAIN PATIENTS ARE ALL VARIABLE BUT HEALTHY INDIVIDUALS ARE ALL QUITE CONSISTENT HOW THEY RESPOND. THIS IS STUDY BY ROGER FILLINGIM AND HIS GROUP WHICH THEY LOOKED AT THE 321 HEALTHY YOUNG ADULTS, USE THE SAME HEAT STIMULUS AND LOOK AT REPORTS OF PAIN, VISUAL ANALOG SCALE, 0 TO 100 POINT SCALE, AND WHICH THEY WONDER WHAT THE PAIN SEVERITY WAS BASED ON STIMULI, THE MEAN WAS 371.8. PAINFUL. BUT WHAT ABOUT THE NUMBERS OF PEOPLE WHO REPORTED DIFFERENT LEVELS OF PAIN? THAT SAMPLE WENT FROM VERY LITTLE PAIN TO 100. WE GOT HEALTHY PEOPLE STANDARDIZE CONTROL STIMULI YET YOU SEE THIS VARIABLE. THE RODENTS ARE SHOWING VARIABILITY, HEALTHY PEOPLE SHOWING VARIABILITY. WHAT ABOUT PATIENTS AS MUCH IS THIS IS ANALYSIS THAT WAS BY GERMAN DUTCH GROUP, GERMAN DUTCH GROUP, THEY LOOK AT 179 DIFFERENT PROCEDURES, SURGICAL PROCEDURES, TOTAL OF 69,708 PATIENTS AND THEY WERE LOOKING AT DIFFERENT SURGICAL INTERVENTIONS AND THAT'S GOING TON THE SIDE OF DIFFERENT SURGERIES THEY ARE LOOKING AT AND THE IMPORTANT THING ABOUT THIS SLIDE IS TO LOOK AT THE RIGHT HAND SIDE, WHICH LOOK AT VARIABILITY AND PAIN RESPONSE TO SAME SURGICAL PROCEDURE, SAME ROUGH POPULATION OF INDIVIDUALS. WHAT YOU CAN SEE IS TWO FOR EACH ONE. ONE IS PAIN ON MOVEMENT AND ONE IS PAIN ON REST. FIRST YOU CAN SEE THERE'S HUGE VARIABILITY IN HOW PEOPLE RESPOND TO THE SAME SURGICAL INTERVENTION, ROUGHLY THE SAME KINDS OF PEOPLE HAVING THE SAME SURGERIES AND THEIR PAIN AT REST AND HAIR PAIN ON AMBULATION. FROM IS QUITE DIFFERENT. SO WHEN WE START THINKING HOW WE OOH EAR GOING TO MEASURE OR ASK SOMEBODY ABOUT THEIR PAIN, THE CIRCUMSTANCE BECOMES IMPORTANT. WE TALKED ABOUT THE BIOPSYCHOSOCIAL MODEL. PERSPECTIVE, WHAT BIOLOGICAL FACTORS IMMEDIATE TO BE ASSESSED IF IN FACT WE WANT THE BIOPSYCHOSOCIAL PERSPECTIVE MODEL, YOU HAVE TO THINK THERE'S BIOLOGICAL FACTORS, WE HEARD OF THOSE, GENERAL DISEASE SPECIFIC FACTORS. WHAT ABOUT PSYCHOLOGICAL FACTORS, WHAT WE SHOULD BE LOOKING AT. YESTERDAY WE HEARD KRISTEN GIVE US INFORMATION ABOUT MOOD. ANXIETY AND WE HEARD ABOUT A LOT OF CATATRAPHIZING, THOSE ARE POTENTIAL PSYCHOLOGICAL VARIABLES. WE WANT TO THEE ABOUT BELIEFS AND EXPECTATIONS AN RESILIENCE WHICH WE ONLY HEARD MENTIONED ONE UPON A TIME. MUCH MORE IMPORTANT TO CONSIDER. WHAT ABOUT THINKING? COGNITION? HOW END POINTS MEMORY, ATTENTION, FOCUS OF ATTENTION. BEHAVIOR, WHAT DO WE DO, HOW IS THAT IMPORTANT TO BE ASSESSED IF WE WANT THE BIOPSYCHOSOCIAL MODEL AS MUCH QUALITY OF LIFE, WE HEARD THAT MENTIONED IN PASSING. WHAT ABOUT SOCIAL PRACTICE WHICH IS MORE DIFFICULT, LESS WELL ASSESSED BUT LOOKING AT SOCIAL FACTORS, SOCIAL SUPPORT OR SIGNIFICANT OTHER RESPONSES, PHYSICAL RESPONSIBILITY THAT PEOPLE HAVE ON THEIR JOB, WHAT WE'RE DOING WITH FAMILY OR HOME VERSUS WHAT YOU TO AT WORK MAYBE QUITE DIFFERENT AND THAT MAYBE IMPORTANT FOR US TO BE LOOKING AT. FINANCIAL RESOURCES AND COMMUNITY RESOURCES IF YOU HAPPEN TO LIVE IN A CITY LIKE SEATTLE THERE'S A LOT OF RESOURCES AROUND IF YOU LIVE IN RURAL MONTANA YOU DON'T HAVE THOSE RESOURCES AND HOW DOES THAT INFLUENCE PEOPLE'S PERCEPTION AND REACTION TO PAIN AND MOW TO RESPOND TO DIFFERENT TREATMENTS AND THEN SOCIETAL NORMS, YOU HEARD ABOUT DIFFERENT RACIAL GROUPS AND SOCIETAL NORMS THERE YOU CAN BE THINKING ABOUT. GIVEN BIOPSYCHOSOCIAL, WHAT'S THE SOURCES OF DATA? WHAT INFORMATION DO WE HAVE FOR THOSE? HISTORY, MEDICAL RECORDS, WE HER ABOUT MEDICAL RECORDS AND WHAT SHOULD BE INCLUDED IN THOSE. WE HAVE SELF-REPORTS OR SURROGATES, WE HEARD LOTS YESTERDAY MORNING ESPECIALLY, SELF-REPORT MEASURES FOR NEONATES OR INFANTS, WE HAVE POTENTIALLY SURROGATES FOR THOSE INDIVIDUALS WHO HAVE SOME TYPE OF PHYSICAL IMPAIRMENT OR MENTAL IMPAIRMENT THEY CAN'T SELF-REPORT, SURROGATES FOR THEM. WE HAVE OBJECTIVE MEASURES, WE HAVE PATHOLOGY AND PHYSICAL FUNCTIONING. WE HAVE PHYSICAL EXAMINATION OR CLINICAL PERFORMANCE SO WHAT IS THE STRAIGHT LEG RAISING, EXAM, A CLINICAL PHYSICAL EXAMINATION MIGHT BE PERFORMANCE TASK OF SOME TYPE, YOU MIGHT HAVE TIME OF THE GO TASK AND THE 25-METER WALK OR DIFFERENT VARIATIONS, THOSE ARE STRUCTURED TASKS THAT WE HAVE. THERE'S A LABORATORY TEST WE HEARD ABOUT SOME OF THE ONES THAT ARE USED OUT THERE. WE HEARD ABOUT SOME INNOVATIVE OPPORTUNITIES THAT ARE THERE. ALL THE IMAGING AND I'M GOING TO SAY THIS TONGUE IN CHEEK, THE IMAGING IS DEVELOPING SO RAPIDLY I CAN'T EVEN KEEP UP WITH THE ACRONYMS LET ALONE UNDERSTANDING WHAT'S GOING ON. WITH SOME OF THESE PROCEDURES. THAT'S WHY WE HAVE EXPERTS HERE. QST, CONDITION PAIN MODULATION, TEMPORAL SUMMATION, THOSE ARE ALL DIFFERENCE TESTS CONDUCTED TO GIVE IDEAS ABOUT QST. THOSE ARE SOURCES OF INFORMATION. AXELROMETRY IS ANOTHER WAY, WE HEARD ABOUT -- DIFFERENT THINGS WE CAN USE, THERE'S ALSO GENETIC KINDS OF INFORMATION THAT IS IMPORTANT AS THE NUMBER OF TIMES AS WELL AS MOUSE STUDIES I SHOWED YOU, THE SPECIFIC GENES OR GWAS, SNPs YOU WANT TO LOOK AT, SELF-REPORT SURROGATE REPORTS OF THEIR ACTIVITIES. THERE'S QUESTIONNAIRES RETROSPECTIVE REPORTS, SO WE CAN ASK RETROSPECTIVELY ABOUT THE PAIN OR FUNCTION, THE LAST WEEK, LAST DAY WHAT IS YOUR MOVEMENT LIKE LAST MONTH, WHAT IS FUNCTION LIKE OVER THE LAST 24 HOURS, THEY HAVE CLINICAL INTERVIEWS AS WELL AS STRUCTURE PROCEDURES. IT'S QUESTIONNAIRES AT REAL TIME ARE UNFORTUNATELY COULDN'T BE HERE WHO IS GOING TO TALK TO US ABOUT USING ECOLOGICAL MOMENTARY ASSESSMENT OR DMA APPROACHES TO GATHER INFORMATION AND BEHAVIORAL OBSERVATIONS THIS COMMUNICATION FROM THE PATIENT, HIM OR HER AND THEIR PERFORMANCE ON TASK THEY ARE COMMUNICATING. THOSE ARE VOLUNTARY THOUGH THEY MAY NOT NECESSARILY BE AWARE THEY ARE VOLUNTARILY BUT WE CAN OBSERVE IN CLINIC. WE CAN OBSERVE IN A NATURAL ENVIRONMENT IS WHAT YOU CAN SEE IN THE DOCTOR'S OFFICE SIMILAR TO THE BEHAVIOR YOU SEE IN THE PERSON WALKING OUT TO THEIR CAR OR SHOPPING MALL OR WORKING AROUND THEIR HOME. SO THOSE ARE POTENTIAL BEHAVIORAL OBSERVTIONS. THE TROUBLE WITH THIS IS I HAVE WHEN I STARTED THIS, THIS HAS BEEN THE PROBLEM WE HAVE IN THE AREA OF PAIN SINCE I BEGAN LONG BEFORE I BEGAN, LONG BEFORE WE HAD A LOT OF DISCUSSION ABOUT PAIN, WHICH IS WHAT ARE THE KINDS OF INFORMATION WE HAVE? WE HAVE A RANGE OF BEHAVIORS, SELF-REPORTS, PHYSICAL PATHOLOGY, GENETIC FACTORS, MORE RECENTLY AND THE TROUBLE WITH THESE ARE NOT HIGHLY CORRELATED. SO WHAT DO WE DO NOW IF WE LOOK AT THESE WHICH IS VALID, WHICH DO YOU BELIEVE? WHICH TELLS THE TRUTH? THAT IS THE WRONG QUESTION. WE SHOULD BE SAYING KNOWING THAT EACH PROVIDE USEFUL BUT DIFFERENT QUESTIONS. FROM THEY ARE COMPLIMENTARY AS WE HEARD AS MENTIONED PREVIOUSLY. THIS IS AN EXAMPLE OF ASSESSING PHYSICAL PUNKS, A WHOLE NUMBER OF PRESENTATIONS ABILITY PHYSICAL FUNCTION, WE HAVE DIFFERENT SOURCES OF DATA, YOU HEARD ABOUT DIFFERENT ONES, YOU HAVE SELF-REPORTED PATIENT, COULD BE SELF-REPORT DNA FORMAT OR RETROSPECTIVE FORMAT, WE HAVE OBSERVATION OF THE PATIENT. WHAT THEY ARE ACTUALLY DOING IS ANOTHER SOURCE OF DATA. WE HAVE CLINICAL ASSESSMENT IMAGING WHICH IS ANOTHER SOURCE OF DATA ABOUT FUNCTION THAT WE CAN USE, THE CLINICAL ASSESSMENT THESE ARE STRUCTURED TASKS THAT ARE PERFORMED. TO GATHER DATA, ALL THESE RELATE TO PHYSICAL FUNCTION AND WE HAVE THE REAL WORLD ASSESSMENT. AXELROMETRY STEP COUNTS ALL WAYS WE CAN GATHER INFORMATION FROM THE PATIENT ABOUT THEIR FUNCTION. QUESTION IS WHAT DO THESE DATA INDICATE WHAT THE DIFFERENT TYPES OF DATA? SELF-REPORT MAYBE TELLING US WHAT'S IMPORTANT TO THE PATIENT. WHAT HE OR SHE IS DOING IN THEIR LIFE OR WHOA HE OR SHE THINKS IS IMPORTANT. MY PAIN IS VERY BAD BUT I FEEL LIKE GOT TO TAKE CARE OF MY CHILDREN AND THEREFORE I DO THINGS TO TAKE CARE OF MY CHILDREN. THEREFORE I SAY FUNCTION RELATED TO CHILD CARE ACTIVITIES ARE IMPORTANT MY SELF-REPORT QUESTIONNAIRE. WHAT ABOUT OBSERVATION AS MUCH THAT'S WHAT THE PATIENT WANTS TO CONVEY. PATIENT COMES TO CLINIC, HE OR SHE KNOWS THEY ARE BEING EVALUATED. MOW THEY ARE BEING OBSERVED. THEY ARE BEING ASKED TO ENGAGE IN VOLUNTARY BEHAVIORS. WHAT THEY LOOK LIKE IN THE CLINIC MAY NOT BE REPRESENTATIVE WHETHER THEY WANT TO LOOK GOOD OR BAD OR RYE TO CONVINCE YOU THAT THEY ARE SUFFERING. THEY ARE BEHAVIOR COMMUNICATES SOMETHING TO THE SOURCE OF DATA. IF YOU DO IMAGING ASSESSMENTS WHAT THE PATIENT ACTUALLY DOES IN A CONTROLLED ENVIRONMENT OF SOME TYPE, CONTROLLED ENVIRONMENT MAYBE CLINIC, MAYBE LABORATORY OF SOME TYPE BUT IT TOOK A CONTROL OF ENVIRONMENT WHAT HAPPENS TO THE PATIENT IN THE THE ENVIRONMENT. THE REAL WORLD ASSESSMENT IS WHAT THE PATIENT DOES. T WHICH ONE OF THOSE IS GIVING INFORMATION. NOT ONE IS BETTER THAN THE OTHER, THEY ARE GIVE US DIFFERENT KINDS OF INFORMATION. FROM COMPLIMENTARY AND PROVIDES USEFUL INFORMATION. IF YOU TAKE ANY ONE OF THOSE AND MAKE INFERENCES YOU ARE GOING TO MISS A LOT OF IMPORTANT INFORMATION. OVERARCHING IF NOTHING ELSE SAVES YOU WAS THIS, WE GOT TO START FOCUSING ON ASSESSING AND EVENTUALLY TREATING THE PERSON EXPERIENCING PAIN NOT JUST THE PAIN. THAT'S THE END USER. HOWEVER, THE QUESTION HOW DO E DO IT? H THAT'S WHAT WE ARE TALKING ABOUT. WHAT ARE SOME GENERAL CONSIDERATIONS AND CONCERN REGARDING ASSESSMENT? WHAT IS -- IS IT A RESEARCH OR CLINICAL QUESTION? I CAN DO RESEARCH STUDY THE DEPTH OF MY WORK IS DIFFER THAN POSSIBLY I WANT TO DO IN CLINIC, EPIDEMIOLOGY STUDIE HAVE DIFFERENT KINDS OF QUESTIONNAIRES, DIFFERENT KINDS OF INFORMATION AND YOU CAN USE IN LABORATORY SETTING. IS WILL AGREEMENT ON THE SPECIFIC DIAGNOSTIC CRITERIA? YOU HAVE CRIST TEN ACUTE PAIN AND THE GOING ON WITH THIS TRYING TO COME UP WITH SOME WAYS OF GETTING US TO STANDARDIZE HOW WE GO ABOUT MAKING DIAGNOSES ABOUT DIFFERENT CONDITIONS, MAKE SURE WE GET GO BEYOND SIMPLE WAY. WHAT IS THE STABILITY OF THE SYMPTOMS AND IMPACT OF FUNCTION? DOES IT CHANGE OVER TIME? IF I SEE IN THE CLINIC IF I SEE ONE WEEK AT A TIME, IS THAT TRUE ABOUT WHAT I WOULD BE SEEING OVER LONGER PERIOD OF TIME? WHAT IS THE DEPTH HOW INTENSE CAN YOU ASSESS? HOW MUCH INFORMATION CAN YOU GATHER? WHAT IS REASONABLE FOR A PATIENT TO BE ASKED? THE OLD MINNESOTA MULTI-PHASE PERSONALS, SOME OF YOU ARE OLD ENOUGH TO REMEMBER, HAVE 556 QUESTIONS. 556 TRUE AND FALSE QUESTIONS. THAT IS A LOT OF BURDEN. CAN YOU MENTION EPIDEMIOLOGY STUDY ASKING PATIENT SUBJECT RESPONDENT? NOT POSSIBLE. SO WE HAVE A COMPLEXITY HOW SIMPLE OR COMPLEX IS WHAT WE ARE ASKING TO DO? WHAT SOMETIMES WE'LL SEE IS SIMPLE PASS ON TO SIMPLE (INAUDIBLE) IT'S A BURDEN, HOW MUCH TIME DOES IT TAKE, HOW COMPLEX -- HOW MUCH TRAINING IS REQUIRE? BY THE FACILITIES -- ARE THE FACILITIES AVAILABLE? THAT IS A GENERAL CONCERN. IS THERE A CONSENT -- CONSENSUS ON THE METHODS, INSTRUMENTS PROCEDURES, TIMING ANALYTICAL METHODS USED THE ANALYTIC INTERPRETATION OF THE DATA, PRESENTATION OF THE INFORMATION. WHAT'S THE ADEQUACY OF -- WHAT IS THE ADEQUACY OF THE (INAUDIBLE) ARE THEY GOOD ENOUGH? HOW DO YOU AGGREGATE INFORMATION FROM LARGE DATA SETS FROM MULTIPLE STUDIES MULTIPLE CLINICS DIFFERENT PLACES AND HAVING COMPETENT WAY OF AGREEING ON THAT? A QUICK (INAUDIBLE) BUT THE FDA WAS INTERESTED ONE POINT IN TIME TRYING TO FIND WAY TO HARMONIZE DATA ACROSS PAIN STUDIES. HOW INFORMATION IS PRESENTED BY THE SPONSORS. SO THEY CONTRACTED A GROUP INVOLVED WITH AND WE HAVE SUBCONTRACT ANOTHER GROUP LONG STORY BUT BOTTOM LINE IT TOOK MONTHS TO GO THROUGH DATA SETS AND WE CONCLUDED WAS SIMPLE THINGS LIKE AGE WAS BEING SUBMITTED IN DIFFERENT WAYS BY DIFFERENT COMPANIES, THEY HAD IT PREPARED SO SOME COMPANIES AGE IN YEARS, SOME WAS YEARS AND MONTHS, SOME BY DATE OF BIRTH. SO IF YOU ARE GOING TO -- ACROSS MULTIPLE STUDIES YOU HAVE TO FIND A WAY TO GET THAT MORE COMMON METRICS USED. SOME EXAMPLES OF CONSENSUS OF METHODS, THERE'S A VARIABILITY IN HOW WE ASSESS IMPACT THAT'S ALSO INTERPRETATION AND PREVALENCE OF THE DATA. DO WE HAVE CONSENSUS? INTENSITY, WE HEARD A LOT CURRENT AT LEAST AVERAGE AT REST, WHAT ACTIVITIES? SOMEONE SAID ACTIVITY. WELL IF YOU TALK ABOUT SOMEBODY WITH A HIP OA THAT YOU MIGHT BE INTERESTED MANY VERY DIFFERENT HAHN SHALL BE WITH SHOULDER (INAUDIBLE). IS IT IN THE THE LAST 24 HOURS, LAST WEEK, LAST THREE MONTHS, HOW DO YOU ANSWER THAT? SELF-REPORT. DO YOU SINGLE ITEM, SHORT FORMS, 15 ITEM FORM, MULTI-PHASE PERSONALITY. HOW INTENSE ARE YOU GOING TO GET? THEY HAVE TO BE DISEASE SPECIFIC OR CAN THEY BE GENERAL? FOR EXAMPLE IF YOU HAVE MOA GENERAL MEASURE OF ACTIVITY OR USE SPECIFIC MEASURES OF -- DEVELOPED FOR THAT. IF YOU HAVE SHOULDER PAIN YOU USE THE DASH BECAUSE THEY ARE SPECIFICALLY DEVELOPED. SO THERE ARE DIFFERENCE ACE CROSS THE ME MEASURE YOU'RE GOING TO USE. WHAT IS THE PAIN IMPACT DURATION OF CLINIC PAIN? WHAT SHOULD HOE CHRONIC PAIN, LEE MONTHS, SIX MONTHS, AT LEAST HALF THE DAYS IN THE LAST SIX MONTHS, DOES IT HAVE TO AFFECT THAT ACTIVITY, YOU SAW MEDICAL CARE, IS IT HIGH IMPACT OR LOW IMPACT. I'M OUT OF TIME. TWO MORE SLIDES, THE PHYSICAL EXAM PROCEDURES. IS THERE INTERRATER RELIABILITY? DO YOU THINK ABOUT THAT OR PEOPLE REPORT ON IT BUT INTERRATER RELIABILITY PHYSICAL EXAMINATION PROCEDURES IS NOT VERY GOOD. SOME PAM EXAMPLES OF CONCERNS, FOR GENETICS YOU DO GWAS, TARGETED GENES DO YOU DO CANDIDATE GENES? WHICH SNPS ARE YOU LOOKING AT, IS THERE ANY CONSENSUS WHAT YOU'RE GOING TO DO? OBSERVATION BY WHOM, WHERE, OR WHAT TIME INTERVAL. IS THERE CONSISTENCY AMONG OBSERVERS? MOM OTHER DEVICE WHAT IS DEVICE WORN HOW LONG WHAT DEFINITION OF TIME, HOW SHOULD THE DATA BE PREPARED FOR ANALYSIS AND WHAT DATA ANALYTIC STRATEGIES CAN YOU USE? SAME TRUE FOR MRI. QUANTITATIVE SENSORY TESTING, GERMAN NETWORK, BET SIDE, MINIMAL APPROACH, WHAT IS RELATIONSHIP WITH SELF-REPORT MEASURES. DR. PREMAN SHOWED US THOSE DATA. CONDITION PAIN MODULATION. WHAT'S THE SOURCE OF THE STIMULATION, WHAT IS THE CONTROL STIMULI ADMINISTERED WHERE AND BY WHOM? WHAT'S THE PREFERENCES. BE AWARE OF NIH. NIH, THE OTHER NIH, NOT INVENTED HERE. WE HAVE OUR PET PROCEDURES, OUR PET DEVICES AND WE WANT YOU TO USE OURS BECAUSE WE HAVE GOT A LOT OF DATA. WE HAVE POTENTIALLY REMARKABLE PRODUCT. SO YOU HAVE TO USE -- DO IT OUR WAY BECAUSE WE KNOW THE BEST. AND THE LAST SLIDE, I'M OVER TIME. THE CONSENSUS ABOUT WHAT WE NEED IS SOME ESSENTIALS IS WHAT ABOUT -- WHAT IS THE NECESSARY SUFFICIENT COMPONENTS OF ASSESSMENT GIVEN ALL THINGS WE HAVE BEEN HEARING ABOUT WHAT IS ESSENTIAL? WHAT IS NECESSARY, WHAT IS SUFFICIENT FOR ALL RESEARCH STUDIES AND THAT'S DIFFERENT FROM WHAT MIGHT BE NECESSARY IN SUFFICIENT FOR CLINICAL PRACTICE AND THAT WOULD BE INCLUDED IN HEALTH RECORDS. WHAT IS SPECIFICATION OF COMMON DATA ELEMENTS. WHAT IS THE MINIMUM THINGS THAT SHOULD BE GATHERED FOR ALL STUDIES THAT ARE PUBLISHED SO THAT IN FACT WE COULD AGGREGATE ACROSS STUDIES. STANDARDIZATION OF CONSTRUCTS. PAIN, CATATRAPHIZING, ANXIETY, DO WE HAVE STANDARDIZATION WHAT CONSTRUCTS ARE, STANDARD AND METHODS AN PROCEDURES OF REPORTING THESE THINGS? WE HAVE A CONSENSUS OF METHODS TO REQUIRE REPORT ANALYZE AND INTERPRET DATA. THESE ARE THINGS NIH NEEDS TO HELP TO FORCE HELPING ENCOURAGING IF YOU WILL US TO BE DOING. RIGHT NOW THERE IS NOT A LOT OF CONSENSUS ABOUT THESE THINGS WHICH MAKES IT EXTREMELY DIFFICULT TO INTERPRET THE INFORMATION THAT WE ARE RECEIVING. I WENT FOUR MINUTES OVER. MY REPUTATION PRECEDES ME. THANK YOU. [APPLAUSE] >> THANKS, DENNIS, I LIKED HOW THESE THREE PRESENTATIONS DOVE TAILD WITH EACH OTHER, WITH RAY'S. MENTIONING MECHANISMS SO IMPORTANT. IF WE END UP WITH SOME ME RICK THAT'S REPLACED SUBJECT SELF-REPORT OF 8 WITH MACHINE SAYING 8 THAT DOESN'T DO THAT MUCH FOR US IF WE GET MECHANISM WE CAN STRATIFY PATIENTS WE CAN TARGET THEIR ISSUE AND THEN FUNCTION, I THINK HAVING METRICS OF FUNCTION IS HUGE, IF SOMEBODY GOES FROM AN 8 TO A 6 AND STILL LAYING IN BED, THAT'S PROBABLY NOT IDEAL. THEN DENNIS IS LOOKING AT ALL SORTS OF VARIABLES IN CONCERT, IN FACT THAT EVERYTHING DOESN'T HAVE TO AGREE WITH ITSELF. THERE'S GOING TO BE FUNNY PATTERNS, SO THE THREE OF YOU REALLY OUTLINED A NICE CHARGE FORWARD. WE HAVE -- HOW LONG FOR QUESTIONS? 11:45. SO WE HAVE TEN MINUTES FOR QUESTIONS. >> TWO QUESTIONS, ONE A LITTLE MORE INVOLVED THAN THE OTHER REALLY QUICK. I'M WONDERING IF YOU HAVE A TRAINING INSTITUTE LIKE DFNS, ARE ALL METHODS PUBLISHED LIKE INSTRUCTIONS TO -- THAT YOU USE INSTRUCTIONS TO THE SUBJECTS OR THE PATIENTS? >> WE DO NOT FROM HAVE A TRAINING INSTITUTE. IN A MANUSCRIPT THAT IS UNDER REVIEW, MOST METHODS ARE INCLUDED THE MANUAL OF INSTRUCTIONS IS NOT BUT IT'S BEEN PART OF VARIOUS PRESENTATIONS LIKE THIS THAT ARE AVAILABLE. WHEN IT'S USED IN A MULTI-CENTER TRIAL, AND USED IN A COUPLE, MAYBE FOUR OR FIVE, THE MANUAL IS MADE AVAILABLE OF COURSE. >> WE HAVE A MULTI-CENTER TRIAL THAT IS SUPPORTED BY THE DOD THAT WE MIGHT WANT TO SHARE. >> THAT'S JUST THE KIND OF COLLABORATION THAT WE WOULD LIKE. >> EXCELLENT. >> DEFINITELY WILL LOVE TO TALK TO YOU. AS I SAY, THE WEAKNESS OF THE PROTOCOL AT THIS POINT, IT'S A WEAKNESS NOT UNIQUE TO BENCH SIDE, IT'S LABORATORY AS WELL, WARMTH AND HEAT. WE ARE IMPROVING THAT. AT THE MOMENT. BUT OTHERWISE, WOULD LOVE TO COLLABORATE. >> EXCELLENT. >> SO FAR COLLABORATIONS ARE ONLY WITHIN INDUSTRY. >> OKAY. THE OTHER QUESTION IS FOR THE PEOPLE USING SENSORS TO MEASURE WALK AND STEPS, ARE THERE ANY DEVICES THAT YOU KNOW OF THAT ARE USED FOR WHEELCHAIR USERS? TO ASSESS NOT STEPS BUT OTHER KINDS OF MOBILITY? >> TYPICALLY THEY DO THINKING OF THE RERC OUT OF PITTSBURG, DEVELOP SENSORS THAT LOOK AT THE PROPULLSIVE VERSUS NON-PROPULLSIVE STROKES IN MANUAL WHEELCHAIR USERS THAT'S WHERE YOU ARE LOOKING AT ACTIVITIES MANUAL WHEELCHAIR USE. BUT I WOULD START COOPER'S GROUP. >> FOR THE RECORD, WHEELCHAIR USERS, IS -- INSTRUMENTED WHEEL THEY USE SIMILAR TO WHAT WE TYPICALLY DO WITH FORCE PLATE IN THE LAB AND RECONSTRUCTED WHEELCHAIR PROPULSION CYCLE TO ESSENTIALLY MATCH GATE WITH LOADING RESPONSE GRABBING VERSUS AN ACTUAL FORWARD PROPULSION. >> SENSOR IS ON THE WHEEL? Q. THE WHEEL IS THE SENSOR. IT'S NOT TRIVIAL BUT WILL GET YOU THAT INFORMATION AN CERTAINLY THERE ARE -- I WOULD IMAGINE PRESSURE SENSORS THAT ONE CAN PUT IN THE HAND AND GET SOMETHING AS SIMPLE AS CONTACT VERSUS NON-CONTACT. MUCH LIKE STANCE SWING THAT'S HOW THE WHEELCHAIR LITERATURE BREAKS UP WHEELCHAIR PROPULSION. >> WONDERING WHAT THE PANELISTS RESPONSE WOULD BE TOP SORT OF THE QUESTION THAT THE -- THERE WAS AER A PAPER PUT UP BY MITCHELL MAX THE IDEA UNDERSTANDING MECHANISM, BETTER TAYLOR AND DEVELOP TREATMENTS BASED ON MECHANISM, THIS IS WHY A LOT OF OUR TREATMENTS ARE FAILING AND WE NEED TO DO A BETTER JOB OF DOING THAT. THAT PAPER I THINK WAS FROM 2001.& IT'S BEEN A FEW YEARS. WHAT DO YOU THINK IS -- ARE THE BIGGEST BARRIERS WHY THAT HASN'T HAPPENED? THIS IS NOT A NEW IDEA. I KNOW IT'S COMPLICATED. TRYING TO BE PROVOCATIVE BUT WHAT HAVE BEEN BARRIERS TO MAIN BARRIERS TO KEEP THAT FROM HAPPENING? >> ASSUME THAT I'M BEING ASKED THIS QUESTION. IT'S A COMPLICATED QUESTION. I WILL TRY TO BE BRIEF ANSWERING IT. I THINK WHY FIRST I'M NOT SURE THE APPROACH HAS BEEN ADOPTED SUFFICIENTLY WELL. I THINK THAT IN PAIN TRIALS BY AND LARGE PATIENTS HAVE NOT BEEN PHENOTYPED WELL. IN PART BECAUSE THE LABORATORY BASED QST IS NOT BEEN PICKED UP BY MANY PEOPLE, AND IN PART BECAUSE IT IS TOO COMPLICATED. NOW, THEN THERE'S BEDSIDE. I -- THE PROBLEM BE BEDSIDE IN A MULTI-CENTER TRIAL IS YOU NEED TO BE CONUSANTLY VIGILANT. WHEN THIS IS BEING DONE, I GIVE A TALK AT START, STILL A LITTLE ENTHUSIASM AND STILL IMPORTANCE OF QST METHOD, THEN I'M OFF THE SCENE, WHO KNOWS WHAT HAPPENS IN A THREE YEAR TRIAL. I TRY AND KEEP THINGS GOING BUT IT'S NOT REALLY MY PRIMARY FOCUS IN A MULTI-CENTER TRIAL, I HAVE GOT -- I DO HAVE ANOTHER LIFE. SO THIS IS WHAT ATTENUATES, THAT'S WHY I WAS SO ENTHUSIASTIC ABOUT COLLABORATING WITH ACADEMIA BECAUSE THAT WILL GIVE A REAL OPPORTUNITY TO COLLABORATE AND PEOPLE WHO ARE ACTUALLY DEDICATED, NOT DOING FOR PROFIT CLINICAL TRIAL. IT MAY B SO THAT IS THE ONE, IT'S LONG ANSWER. I'LL BE BRIEF WITH THE SECOND ONE, IT MAY BE THAT THE MECHANISM BASED APPROACH ACTUALLY IS NOT TRUE. THE PHENOTYPE IS TOO COMPLICATED TO DERIVE, THE SAME PHENOTYPE MAY HAVE SEVERAL UNDERLYING MECHANISMS THE SAME APPLIESES TO A SIGNATURE THAT YOU MAY SEE ON FMRI FOR EXAMPLE, BUT IT'S JUST THAT WE DON'T HAVE SUFFICIENT GRANULARITY AT THIS POINT IN DELINEATING THE MECHANISM PHENOTYPE CONNECTION. I THINK THOSE ARE THE TWO IMPORTANT POINTS. OR THREE, NOT HIGHLY ADOPTED, WHEN ADOPTED NOT SURE IT'S EXECUTED AS WELL AS IT CUBE. AND THREE, WE MAY NOT BE SUFFICIENT GRANULARITY WHICH RELATES TO ADOPTION QUESTION AS WELL. I DON'T KNOW IF THAT ANSWERS YOUR QUESTION. >> A CLINICAL PIECE TO THIS, A GREAT AMOUNT OF THE RESEARCH HISTORICALLY AS ANALGESIC TREATMENTS MED BY PHARMACEUTICAL INDUSTRY, IT'S HISTORICALLY SAID WE WANT TO HAVE A DRUG FOR POPULATION X. THAT'S A LARGE POPULATION. THEY DON'T WANT TO BE TOLD WELL, YOU GOT A DRUG BUT ONLY 25% OF POPULATION. THEY ARE STARTING TO CHANGE THEIR UNDERSTANDING BUT INITIALLY THAT WAS THE FIRST RESPONSE REACTION I HEARD WAS THAT WE DON'T -- WE WANT TO HELP USEFUL FOR EVERYBODY. WE DON'T WANT TO GO TO THE FDA AND TRY AND GET INVOCATION FOR SUBTYPE OF THESE PATIENTS BECAUSE THAT'S GOING TO POTENTIALLY HAVE IMPACT ON OUR RESEARCH MONEY DEVELOPING HOPEFULLY THAT'S CHANGING BUT THAT WAS AN OLD PERSPECTIVE THAT I DID HEAR MANY TIMES. >> IF I CAN ELABORATE ON THAT PRECISE POINT. THE INTEREST IN PHENOTYPING REALLY BEGAN WHEN THE CLINICAL TRIALS BEGAN FAILING, THERE'S A NUMBER OF REASONS WHY CLINICAL TRIALS FAIL BUT SUDDENLY THE NOTION OF GOING FROM A GENERAL -- A GENERALIZABLE APPROACH, WE WANT OUR DRUG TO FIT EVERYBODY TO PERHAPS A LITTLE BIT MORE COMPLICATED THAN THAT. AND MAYBE BE THERE WAS NOT A ONE GLOVE FITS ALL. >> MAYBE I CAN NUANCE ROYS COMMENTS ON MECHANISMS. IT APPEARS TO ME WE HAVE BEEN TOO LIMITED TRYING TO ASSESS THE UNDERLYING MECHANISMS OF A VARIETY OF PRODUCT PAIN CONDITIONS. IT MAY BE IMPORTANT TO BROADEN OUR PERSPECTIVE BEYOND QST LOOKING AT BIOPSYCHOSOCIAL PSYCHOLOGICAL VARIABLES, I'M CURIOUS WHETHER -- I KNOW THE GERMAN NETWORK IS NOT YET, I NO E THERE'S CONSIDERATION BEGINNING TO BRING IN BIOPSYCHOSOCIAL COMPONENTS, IT APPEARS MANY THE NEUROPATHIC PAIN FIELD THERE IS NOT BEEN LARGE EFFORT TO LOOK AT PSYCHOSOCIAL VARIABLES COMBINED WITH QST THAT CREATED OPPORTUNITY TO UNDERSTAND THE MECHANISM MECHANISMS THAT UNDERLIE THE CONDITION. EASILY ASSESSED IN THE BIOPHYSICAL WORLD VERSUS THOSE WHICH WE PUT IN THE PSYCHOLOGICAL BUT REAL BIOLOGY BEHIND IT. IT IS SOMETHING WE AS A -- MAYBE AN OUTCOME OF THIS WORKSHOP WOULD BE TO THINK DIFFERENT DOMAINSES AUTONOMIC PSYCHOSOCIAL QST TO GET BETTER PRESIGNATURE FOR WHATEVER METRIC WE ARE INTERESTED IN. >> I COULDN'T AGREE MORE. DENNIS NIH FOCUSES MARROWLY ON INTEREST AND EXPERTISE. I THINK PAIN IS OBVIOUSLY MUCH MORE COMPLICATED THAN ONE CAN ASSESS WITH ONE TECHNIQUE. >> JUST A COMMENT THAT DENNIS EXCELLENT PRESENTATION ON SOME OF THE CONCERNS. I VIEW THOSE AS OPPORTUNITIES. THESE ARE OPPORTUNITIES FOR RESEARCH TO DETERMINE WHICH OF THESE DOMAINS ARE OF IMPORTANCE AND THE BEST WAY TO MEASURE. SOME OF THESE DOMAINS. WITHIN THE CONTEXT OF THIS IT'S VERY IMPORTANT TO KNOW WHAT WE WANT TO USE THOSE MEASUREMENTS FOR. DIAGNOSIS, PREDICTION OF TRAJECTORIES, PREDICTION OF DRUG RESPONSE, SO THERE ARE CHALLENGES ACROSS DOMAINS THAT REPRESENTED BUT I THINK WE NEED TO ALSO CONCEPTUALIZE WHAT WE WANT THEM TO TELL US. AND BEGIN TO DIG INTO THOSE DEEPER. >> IT'S THEY SAID WE HAVE A HARD STOP AT 11:45, SHE'S LOOKING AT ME, IT'S 11:46. PLEASE JOIN ME IN THANKING OUR SPEAKERS. WE ARE COMING BACK AT 12:30. >> WE'RE READY TO START SESSION 8. DR. WILL AKLIN FROM NIDA. I WANT TO THANK BILL AN WENDY FOR THEIR LEADERSHIP ON THIS EFFORT, THIS VERY TIMELY, REALLY BEEN CHAMPIONS FOR ENSURING BEHAVIORAL RESEARCH REMAIN A NATIONAL PRIORITY. OUR FIRST -- NEXT SESSION IS WHAT IS EFFICACY AND PAIN CLINICAL TRIALS, IT COVERS FDA, WE HAVE REPRESENTATION FROM FDA, PHARMA, AS WELL AS ACADEMIA, REALLY SPANS THE GAMUT THERE. OUR FIRST PRESENTER IS DR. PAPADOPOULOS WHO SERVES AS THE ASSOCIATE DIRECTOR OF CLINICAL OUTCOME ASSESSMENT. IN THE OFFICE OF NEW DRUGS AND CENTER FOR DRUG EVALUATION AND RESEARCH. THE STAFF PROVIDES CONSULTATIONS TO CDER REVIEW DIVISION AS WELL AS OTHER FDA CENTERS ON CLINICAL OUTCOMES REGARDING DEVELOPMENT, VALIDATION AND INTERPRETATION OVERALL STABILITY AND SUPPORTING LABELING CLAIMS. ALSO MANAGES THE DRUG DEVELOPMENT QUALIFICATION PROGRAM. I WANT TO INTRODUCE DR. PAPADOPOULOS. >> THANK YOU SO MUCH. VERY HAPPY AND HONORED TO BE HERE. I'M HERRING A LOT, I LEARNED A LOT OVER THE PAST COUPLE OF DAYS AND JUST GREAT FOOD FOR THOUGHT TO TAKE HOME BACK TO THE FDA TO TRY TO MOVE SCIENCE AND MEDICAL PRODUCT DEVELOPMENT FORWARD. I AM NOT RESEARCHER, I'M A CLINICIAN AND HAVE PUBLIC HEALTH EXPERIENCE AS WELL AS MEASUREMENT EXPERIENCE. I WILL APPROACH MY PRESENTATION FROM A LITTLE MORE GENERAL PERSPECTIVE YOU WON'T SEE DATA OR ANYTHING IN MY TALK BUT JUST TO SORT OF TAKE A STEP BACK DISCUSS WHAT WE LOOK FOR IN A REGULATORY SETTING IN TERMS OF OUTCOME MEASURES AND END POINTS. TITLE MY TALK IS PATIENT CENTERED OUTCOME MEASUREMENT IN ERA OF PATIENT FOCUSED DRUG DEVELOPMENT. MY DISCLAIMER SO I WOULD LIKE TO START WITH A GENERAL DISCUSSION ON MEASUREMENT OF CLINICAL BENEFIT. FROM A REGULATORY PERSPECTIVE. THEN I WILL GO INTO THE PATIENT FOCUSED DRUG DEVELOPMENT INITIATIVE AND HIGHLIGHT THE KEY ISSUES, MANY RELEVANT FOR THIS AUDIENCE IN TERMS OF GUIDANE FORTHCOMING. DRUG DEVELOPMENT TOOL QUALIFICATION PROGRAM ALLUDED TO EARLIER TODAY. ALSO SOME NEWER PILOTS THAT WE HAVE IN DEVELOPMENT OF CORE CLINICAL OUTCOME SETS WITHIN CDER. STEP BACK AND COME HOME TO THE THE DEFINITION OF PATIENT FOCUSED OUTCOMES WHICH WAS CRAFTED IN 2013 AND HOLDS TRUE. IT'S DEFINED HERE AS OUTCOMES IMPORTANT TO PATIENT SURVIVAL FUNCTION OR FEELINGS AS IDENTIFIED OR AFFIRMED BY PATIENTS THEMSELVES OR JUDGED TO& BE IN PATIENT'S BEST INTEREST BY PROVIDERS AND CAREGIVERS WHEN THEY CANNOT REPORT FOR THEMSELVES. I THINK THIS IS JUST VERY GOOD TO SORT OF GROUND THE CONVERSATION. BROADLY SPEAKING IN TERMS OF EFFICACY, ASSESSMENT, OUR PURPOSE IS REALLY TO DEMONSTRATE CLINICAL BENEFIT SO THIS IS THE BASIC PREMISE FROM OUR PERSPECTIVE HOW WE APPROVE MEDICAL PRODUCTS AND DRUGS. THEY DEFINE IT AS POSITIVE CLINICALLY MEANINGFUL EFFECT INTERVENTION ON HOW PATIENT FEELS FUNCTIONS, OR SURVIVES, AND BY FUNCTIONING OF COURSE YOU MEAN FUNCTIONING IN THEIR DAILY LIVES. NOT ORGAN FUNCTIONING NECESSARILY BUT REALLY HAVE THEY -- HOW THEY FUNCTION IN THEIR ENVIRONMENT. SO THE TOOLS WE USE ARE CLINICAL OUTCOMES ASSESSMENTS. THIS SLIDE SUMMARIZES THE TYPES OF CLINICAL OUTCOME ASSESSMENTS THAT WE USE. THESE DEFINITIONS CAN BE FOUND IN A RESOURCE CALLED THE BEST GLOSSARY WHICH IS A HARMONIZED RESEARCH BETWEEN FDA AND NIH TO TRY TO COME UP WITH A COMMON TAXONOMY HOW WE TALK TOOLS SUCH AS BIOMARKERS AND CLINICAL OUTCOME ASSESSMENTS AND ENPOINTS. YOU CAN SEE HERE HOW WE CATEGORIZED THE CLINICAL OUTCOME ASSESSMENT TOOLS NAMELY INTO FOUR TYPES, MANY OF THESE HAVE BEEN DISCUSSED AT LENGTH. SO I WON'T REALLY GO INTO THEM OTHER THAN TO SAY JUST ECHO PREVIOUS PRESENTERS THAT WE RELY ON ALL THESE TOOLS. NO ONE IS REALLY USED IN ISOLATION AND MEDICAL PRODUCT DEVELOPMENT. I ALSO LIKE TO HIGHLIGHT FOOTNOTE IN THIS SLIDE INCREASINGLY WE ARE SEEING DIGITAL HEALTH TECHNOLOGY TOOLS, THE MONITORING DEVICES, THAT SUCH AS ACTIVITY MONITOR, SLEEP MONITORSSH ET CETERA, THAT CAN ALSO BE USED TO COLLECT OUTCOMES OF IMPORTANCE TO PATIENTS. AND IN THEIR DAILY LIVES. THE REASON I PULLED THIS OUT IS THAT THESE TYPES OF TOOLS MONITORING TOOLS, DON'T NEATLY FIT INTO ANY OF OUR OTHER FOUR CATEGORIES HERE. THEY ARE NOT REPORTED. BY A HUMAN. AND THEY ARE NOT PERFORMANCE OUTCOMES IN THE SENSE THAT THEY ARE TASK BASED. THE KEY FEATURE OF THE PERFORMANCE OUTCOME IS REALLY THAT IT'S A STANDARDIZED TASK PERFORMED BY A PATIENT. OF COURSE YOU COULD USE DIGITAL HEALTH TOOLS TO CAPTURE PATIENT REPORTED OUTCOMES PERFORMANCE TASKS AND SO ON BUT REALLY THE ONES THAT DON'T FIT ARE THE WEARABLES. SO WE HIGHLIGHT THAT HERE. REGARDLESS OF THE TYPE OF CLINICAL OUTCOME ASSESSMENT, WE HAVE GOOD MEASUREMENT PRINCIPLES. THESE ARE HIGHLIGHTED IN THE FDA GUIDANCE OF 2009, IT DESCRIBES HOW WE CONSIDER THESE MEASUREMENT PRINCIPLES, IN PATIENT REPORTD OUTCOME MEASURE EVALUATION FOR REGULATORY USE. REPORTED WE CONSIDER CONTENT VALIDITY WHICH IS HOW WELL DOES THE INSTRUMENT CAPTURES THE CONCEPT. CONSTRUCT VALIDITY, HOW WELL DOES IT ACTUALLY PERFORM IN CAPTURING THAT CONCEPT. RELIABILITY AND ABILITY TO DETECT CHANGE. HOW DO WE INTERPRET THAT CHANGE. ALL THESE AS I MENTIONED APPLY TO MEASUREMENT BROADLY. FDA GUIDANCE IS BEST PRACTICE GUIDANCE. WE ARE CORPLY, I WILL SPEAK LATER IN THE TALK DEVELOPING A GUIDANCE SERIES WHICH HIGHLIGHTS NOT ONLY THE OTHER TYPES OF COAs BUT ALSO MAYBE SOME WAYS WE CAN EXERCISE A LITTLE BIT MORE FLEXIBILITY AND HOW WE LOOK AT CLINICAL OUTCOME ASSESSMENTS WHILE STILL ENSURING THEY ARE APPROPRIATE FOR THEIR INTENDED USE. >> I LOVE THIS SLIDE, IT BASICALLY SHOWS THE TYPES OF CLINICAL OUTCOMES ASSESSMENTS, PRIMARILY AS MEASURED IN CLINIC, HOW WE HAVE NOVEL APPROACHES INCREASE FLEXIBILITY AND HOW WE CAPTURE PATIENTS FUNCTIONING IN THEIR LIVES. THIS IS HUE LIGHTED FROM SENIOR LEADERSHIP IN OUR AGENCY DR. GOTTLIEB, HE HIGHLIGHTS MORE INNOVATIVE METHODS AND OPPORTUNITIES TO MODERNIZE HOW WE DEVELOP MEDICAL PRODUCTS, INCLUDING ELECTRONIC PATIENT REPORTED OUTCOMES AND THOSE HAVE BEEN A WHILE. AROUND FOR A LONG TIME BUT ALSO THE WEARABLES THAT CAN COMPLIMENT THE PATIENT REPORTED OUTCOME MEASURES PROVIDING THIS& OPPORTUNITY TO CAPTURE PATIENTS IN THEIR LIVED EXPERIENCES. AND TO REALLY PROVIDE THAT ADDITIONAL DIMENSION THAT CAN BE VERY IMPORTANT. SO I ALSO WANTED TO HIGHLIGHT, THIS HAS A LOT OF IMPLICATIONS FOR HOW DRUGS CAN BE DEVELOPED. SOME OF THE IMPORTANT IMPACTS OF THIS TECHNOLOGY IS THAT IT CAN REALLY HELP US AGAIN CAPTURE WHAT IS IMPORTANT AND WHAT MATTERS TO PATIENTS IN THEIR DAILY LIFE IN BETWEEN CLINIC VISITS IN THIS ARTIFICIAL SETTING AS WE HAVE BEEN DISCUSSING FOR THE PAST TWO DAYS. IT ALSO REALLY REDUCE -- HAS POTENTIAL TO REDUCE THE BARRIER TO CLINICAL TRIAL PARTICIPATION. WE KNOW TRAVEL TIME AWAY FROM WORK OR OTHER ACTIVITIES CAN BE A HUGE BARRIER, A LOT OF TIMES ELDERLY PATIENTS OR OTHER PATIENTS WHO MAY HAVE SOME REALLY DEBILITATING CONDITIONS ARE ABLE TO EASILY PARTICIPATE SO CAN WE LEVERAGE THESE TECHNOLOGIES AND METHODS TO ENHANCE THEIR REALLY THE REPRESENTATIVENESS OF OUR CLINICAL TRIALS CAN WE HAVE MORE INCLUSIVE GENERALIZABLE TRIALS USING THIS. SO NEXT I WANT TO HIGHLIGHT SOME OF THE DRUG DEVELOPMENT PATIENT FOCUSED DRUG DEVELOPMENT INITIATIVES OTHERWISE MOAN AS PFDD I THINK IT'S BEEN INCREASINGLY RECOGNIZED OVER MANY YEAR NOW PATIENTS AND CAREGIVERS HAVE INCREASING ROLE IN DRUG DEVELOPMENT, IT'S RUE ACROSS THE LIFE CYCLE OF DRUG DEVELOPMENT FROM THE EARLY TRANSLATIONAL PHASES PRE-COMPETITIVE STAKEHOLDER ENGAGEMENT LOOKING AT NATURAL HISTORY, LOOKING AT THERAPEUTIC TARGETS FOR DRUGS. FIGURING OUT WHAT IS IT THAT MATTERS TO PATIENTS AND CAREGIVERS THAT WE SHOULD BE LOOKING AT AND EVEN DEVELOPING TOOLS OR SELECTING TOOLS FOR OUR MEDICAL PRODUCT DEVELOPMENT. EVEN BEYOND THAT WHAT IS MEANINGFUL, PATIENTS CAN HAVE A HUGE -- CAN ADVISE US ON WHAT DEGREE OF CHANGE IN SOME OF THESE MEASURES REALLY MATTERS TO THEM. THEY CAN INFORM US OF UNMET NEEDS, TOLERANCE TO RISK WHAT THEY LOOK FOR, BENEFITS AND THEIR EXPERIENCE POST APPROVAL SO IT'S REALLY A CROSS THE LIFE CYCLE OF MEDICAL PRODUCT DEVELOPMENT. IN TERMS OF THE PFED INITIATIVE, THIS HAD ITS ROOTS IN THE FIFTH AWE TOMMIZATION OF PDUFA. IT REALLY AIMED TO MORE SYSTEM MACKICALLY GATHER PATIENTS' PERSPECTIVES ON THEIR CONDITION AND AVAILABLE THERAPIES WHAT THEY LOOK FOR, AGAIN, AND WHAT THE RISKS TOLERANCE IS IN TERMS OF HOW THEY LOOK AT THESE TREATMENTS. THIS IS HELPFUL IN UNDERSTANDING REALLY THE THERAPEUTIC CONTEXT. GETTING PATIENTS PERSPECTIVES TO HELP US LOOK AT THE BENEFIT RISK OF WHEN WE ARE ACTUALLY WEIGHING REGULATORY NOTION. SO UNDER THIS INITIATIVE FDA COMMITTED TO HOLD LARGE PUBLIC MEETINGS WITH PATIENS AND CAREGIVERS, THESE WERE IN CHRONIC DISEASE AREAS EACH MEETING FOCUSED ON A SPECIFIC DISEASE. AND IT OCCURRED OVER A FIVE YEAR PERIOD. AND THESE ARE -- THESE WERE DISEASES WHERE THERE WERE SYMPTOMATIC, THERE'S UNMET NEED AND REALLY A NEED TO HEAR FROM PATIENTS THEMSELVES ABOUT WHAT MATTERS TO THEM, WHAT THE BURDEN OF THE DISEASE IS, WHAT THE BURDEN OF THE TREATMENTS ARE, AND WHAT THEIR VIEWS WERE UNMET NEEDS. SO REALLY AN OPPORTUNITY FOR THE FDA REVIEWERS TO BASICALLY LISTEN WHAT THE PATIENTS WERE TELLING US ASK QUESTIONS, PRIMARILY LISTEN AND AS A RESULT OF THIS EACH OF THESE PUBLIC MEETINGS HAVE HAD A SUMMARY WITH PATIENT REPORT WHICH IS PUBLICLY AVAILABLE SEEING READ HEM AND PROVIDE VERY RICH PATIENT NARRATIVES WITH QUOTATIONS FROM PATIENTS THAT WHILE IT'S NOT A FORMAL SCIENTIFIC SURVEY, STILL PROVIDES SOME PERSPECTIVES THAT MAYBE WE DIDN'T RECOGNIZE PREVIOUSLY. I THINK WE ALL LEARNED A LOT FROM THESE MEETINGS. SOME OF THE MEETINGS OF COURSE THERE WERE MORE HAHN 20 ACROSS THESE AREAS BUT I HIGHLIGHT A FEW OF THESE BECAUSE HAY ARE SORT OF RELEVANT TO TODAY'S DISCUSSION ON CHRONIC PAIN MEETING, NOT LONG AGO, WE ALSO HAD A MEETING WITH PATIENTS FIBROMYALGIA, WE HAD ONE WITH PATIENTS NEUROPATHIC PAIN ASSOCIATED WITH PERIPHERAL NEUROPATHY AND A RANGE OF OTHER DISEASES WHERE PAIN IS ALSO A PROMINENT FEATURE SICKLE CELL AND GASTRO INTESTINAL DISORDERS AND SO WE HEARD REALLY A LOT OF -- THERE WERE SPECIFIC CONCERNS BUT A LOT OF COMMON CONCERNS ALSO IN TERMS OF THE PROFOUND IMPACT ON MANY DOMAINS OF HEALTH. I WON'T TWO THROUGH THEM BUT HIGHLIGHTING A LOT OF THE SAME THINGS WE HAVE BEEN DISCUSSING IN THE PAST TWO DAYS. AND SO I THINK THAT WE HAVE HAD A LOT OF LEARNINGS AND REALLY OPENED OUR EYES TO PERHAPS DIFFERENT END POINTS THAT WEREN'T TRADITIONALLY BEING MEASURED BUT WE MIGHT WANT TO MEASURE IN THE FUTURE. WITH PDUFA GOING FORWARD, THIS REALLY DOES PLACE US IN A MUCH MORE ACTIVE PARTICIPANT ROLE IN DRUG DEVELOPMENT AND THIS -- THESE ARE SOME OF THE REQUIREMENTS IN PDUFA 6 AND 21ST CENTURY CURES LEGISLATION, I HIGHLIGHTED TWO OF THESE COLLECTING AND ANALYZING PATIENT EXPERIENCE DATA AS WELL AS DRUG DEVELOPMENT TOOL MODIFICATION. THIS IS A DOCUMENT HIGHLIGHTING TIMETABLE FOR ISSUE WEDNESDAY OF GUIDANCE. WHICH I'LL JUST DESCRIBE AS AN OVERVIEW HERE. UNDER THE LEGISLATION WE HAVE A SERIES OF GUIDANCES, EACH SORT OF BUILDING ON A PREVIOUS ONE. THE FIRST ONE -- FIRST TWO HAVE BEEN ISSUED IN DRAFT, THEY ARE AVAILABLE AND ON THE WEBSITE. STARTING OFF WITH HOW DO WE SAMPLE PATIENTS TO REPRESENT THE PATIENT -- TARGET PATIENT POPULATION. THE SECOND ONE IS ELICITING INPUT FROM PATIENTS UNBIASED COMPREHENSIVE WAY, GUIDANCE NUMBER 3 IS -- WILL BE ACTUALLY REPLACING THE PIRO GUIDANCE WHEN FINAL AND THAT ONE IS ALSO IN PROGRESS AND GUIDANCE FOUR FOCUSES ON ONCE YOU HAVE THE MEASURE HOW DO YOU THEN INCORPORATE IT INTO AN END POINT THAT'S INTERPRETABLE AND MEANING FUL. I HAVE AT THE END OF THE TALK WEB LINKS WHERE YOU CAN GO TO THE WEB PAGE AND THERE HAVE BEEN PUBLIC MEETINGS ASSOCIATED WITH EACH OF THESE GUIDANCE DOCUMENTS AND DISCUSSION DOCUMENTS, SO YOU CAN VIEW THOSE AT YOUR LEISURE. NOW I WOULD LIKE TO JUST TALK A LITTLE BIT MORE ABOUT THE DRUG DEVELOPMENT TOOL QUALIFICATION PROGRAM, QUALIFICATION IS DEFINED AS A CONCLUSION THAT WITHIN CONTEXT OF USE, THE TOOL DRUG DEVELOPMENT TOOL CAN BE RELIED UPON TO HAVE A SPECIFIC INTERPRETATION AND APPLICATION WITHIN DEVELOPMENT AND REGULATORY REVIEW. SO BASICALLY THIS ALLOWS US TO REVIEW A TOOL, BIOMARKER, COA, OR OTHER DRUG DEVELOPMENT TOOLS SUCH AS ANIMAL MODEL THAT ESSENTIALLY ALLOWS US TO REVIEW OUTSIDE THE CONTEXT OF ANY INDIVIDUAL DRUG DEVELOPMENT PROGRAM BUT FOR USE MORE BROADLY WITHIN THE CONTEXT OF USE. SO WE CAN REVIEW IT, QUALIFY IT FOR THE CONTEXT OF USE AND THEN DRUG DEVELOPERS CAN HAVE ASSURANCE THAT WE HAVE AGREED TO THIS CONTEXT OF USE. SO THEY CAN BE AS I SAID, IT CAN BE REALLY AN EFFICIENT PATHWAY, IT DOES TAKE SOME TIME TO GO THROUGH THIS PATHWAY BUT ULTIMATELY THE AIM IS TO INCREASE SUFFICIENCY. UNDER 21ST CENTURY EXCUSER WE HAVE A FORMALIZED PROCESS HERE, I WON'T GO THROUGH THE STEPS BUT YOU CAN VIEW THIS ON OUR WEB PAGE. FINALLY, I WANTED TO HIGHLIGHT A NEW PILOT PROGRAM THAT WE HAVE TO DEVELOP CORE CLINICAL OUTCOME ASSESSMENTS AND THEIR RELATED END POINTS. THERE HAVE BEEN -- THERE IS A NEED TO HAVE MORE CONSISTENT FIT FOR PURPOSE END POINTS AND SO WE HAVE FUNDED THREE AREAS OF UNMET NEED. ONE WAS MIGRAINE TO DEVELOP CORE OUTCOMES FOR THAT PARTICULAR DISEASE. ACUTE PAIN IN INFANTS AND YOUNG CHILDREN, THIS IS AN AREA, OF HUGE UNMET NEED, THAT WE DON'T REALLY HAVE VERY GOOD MEASURES IN THESE VERY YOUNG CHILDREN UNDER THE AGE OF TWO FOR US TO APPROVE DRUGS AND FINALLY WE HAVE PHYSICAL FUNCTIONING IS ANOTHER AREA THAT WE ARE LOOKING AT USING A VARIETY OF TOOLS PATIENT REPORTED AND PERFORMANCE BASED. SO IN TERMS OF FUTURE DIRECTIONS SEE US CONTINUE TO ELICIT THE INPUT OF PATIENTS IN SHAPING DRUG DEVELOPMENT AT ALL STAGES. I SEE CONTINUED MULTI-DISCIPLINARY AND MULTI-STAKEHOLDER COLLABORATION. TO ADVANCE THE SCIENCE INCLUDING THEIR GROWTH AND DEVELOPMENT -- DRUG DEVELOPMENT QUALIFICATION PATHWAY AND ALSO WORKING ANOTHER ENVIRONMENT SUCH AS THE CLINICAL OUTCOME ASSESSMENTS AND RELATED END POINTS CORE OUTCOME ASSESSMENT PILOT. ALSO INCREASE ROLE OF TECHNOLOGY SUCH AS WEARABLE SENSORS AN REMOTE ASSESSMENTS. FOR DRUG DEVELOPMENT. WITH THAT I THANK YOU FOR YOUR ATTENTION. THANKS. [APPLAUSE] >> DR. PAPADOPOULOS FOR THAT THOROUGH OVERVIEW AND THE FDA PERSPECTIVE. VERY MUCH. OUR NEXT PRESENTER ON BEHALF OF DR. ARTHUR STONE IS DR. DR. (INAUDIBLE) WE'RE GOING TO CHANGE THE BATTING ORDER. WE ARE GOING TO HAVE DR. SCHOLZ WHO IS -- >> BILL IS GOING TO COVER THAT. DR. SCHOLZ WILL PRESENT ON OBJECTIVES AND END POINTS OF CLINICAL TRIALS IN PAIN PROOF OF BIOLOGY, EFFICACY AND IMPACT. DR. SCHOLZ IS THE ASSOCIATE MEDICAL DIRECTOR IN THE EMERGING NEUROSCIENCE RESEARCH UNIT AT BIOGEN, THE FUNCTION IS RESPONSIBLE FOR EARLY CAREER AND EARLY TREATMENT, EARLY TREATMENT DEVELOPMENT IN THE TARGET AREA OF PAIN. HE STARTED HIS CAREER IN PAIN RESEARCH AND NEUROLOGY AND PSYCHIATRY AT THE MEDICAL UNIVERSITY OF UBICK IN GERMANY. HE STARTED CAREER IN PAIN AS WELL AS NEUROPLASTICITY OF RESEARCH. DR. SCHOLZ RECEIVED RESEARCH GRANTS FROM NIH, THOMPSON FAMILY FOUNDATION AND PHARMA, WELCOME DR. SCHOLZ. >> THANK YOU. >> FIRST ON THE AGENDA FOR THIS WORKSHOP I WAS FLATTERED. THANK YOU FOR INVITING ME AS THE ONLY REPRESENTATIVE OF THE INDUSTRY. BUT I WAS ALSO SCARED AS EVERYTHING WE DISCUSSED TODAY AND YESTERDAY WITH ENORMOUS IMPACT ON THE WAY WE DEVELOP DRUGS IN THIS FIELD EVEN IF WE -- WHEN WE ARE ABLE TO IMPLEMENT THE FRACTION OF -- WE CHANGE THE WAY WE MEASURE PAIN, WE HAVE TO CHANGE TRIAL DESIGN, WE HAVE TO THINK HOW WE ACQUIRE AND ANALYZE DATA AND SUPPLEMENT PATIENTS OPERATIONS. WE HAVE TO RETHINK OUR NEGOTIATIONS WITH THE FDA FOR APPROVAL OF THE DRUGS SO I WANT TO ENCOURAGE YOU TO ENGAGE OUR INDUSTRY STAKEHOLDERS IF YOU EXPECT TO TRANSFORM THESE FINDINGS INTO REALITY. THE GRAPH ON THE RIGHT SIDE, IS NOT THE BEST ANALOGY BUT I JUST WANTED TO HIGHLIGHT THAT EVEN A GREAT IDEA CAN TAKE A LONG TIME TO BECOME REALITY, CPOD IS A MOLECULAR TARGETED MIGRAINE FIRST DISCUSSED FOR ITS ROLE IN PATHOPHYSIOLOGY OF DISEASE IN 1985. THE FIRST TREATMENT TARGETED IN MIGRAINE, IT'S ANTIBODY FOR RECEPTOR OF THIS MOLECULE, IT WAS APPROVED IN 2018. . SO WE ARE TALKING A LONG TIME PLEASE INVITE ME AGAIN AND INVITE MY COLLEAGUES AND I ALSO VERY PLEASED TO HAVE (INAUDIBLE) HERE REPRESENTATIVE OF THE I WANTED TO TUCK ABOUT TRIAL OBJECTIVES. I WILL PRESENT SOME EXAMPLES HOW WE CAN TARGET WHAT'S THE RIGHT DRUG TO RIGHT PATIENT. I CANNOT TALK ABOUT OTHER OBJECTIVES I EQUALLY THINK ARE IMPORTANT FOR EXAMPLE IT WOULD BE NICE TO HAVE A SPECIFIC TREATMENT TO RELIEVE PAIN DEPRESSION ANXIETY OR SLEEP DISTURBANCE. WE HAVE SOME SUCCESS WITH DISEASE MODIFYING TREATMENTS THAT I WILL HIGHLIGHT. I ALSO WANTED TO MENTION ONE TRIAL OBJECTIVE CAN BE IMPROVEMENT OF SAFETY AND TOLERABILITY OF THE TREATMENT ITSELF. RECENT EXAMPLES OF COX-2 INHIBITORS OR MU OPIOID RECEPTOR AGONIST TO ACHIEVE PCR SIGNAL. OPIOID SPARING IS A MORE RECENT TRIAL OBJECTIVE IN THE FIELD OF PAIN, WE HAD IMPACT WORKSHOP ON IT, REALIZED IT'S NOT SO EASY TO DETERMINE WHAT IS CLINICALLY SIGNIFICANT SPARING OPIOID USE. AS FAR AS WE KNOW IT IS ONE OF THE -- AT THE FDA. I HAVE THREE SLIDES ON BIOMARKERS AND HOPE TO CONVINCE YOU THE NOTION THAT THERE ARE NO BIOMARKERS FOR PAIN IS NOT EXACTLY TRUE. WE DON'T HAVE A BIOMARKER FOR PAIN ITSELF. WE HAVE BIOMARKERS FOR PAIN MECHANISMS AND TREATMENT& RESPONSE AND WE ARE USING THOSE TO INCREASE EFFICIENCY OF TRIAL DESIGN. BRIEF NOTE ON PAIN SEVERITY. BEFORE I JOINED BIOGEN I WAS PART OF THE TASK FORCE OF THE INTERNATIONAL ASSOCIATION FOR STUDY OF PAIN. TO IMPLEMENT SYSTEMATIC CLASSIFICATION OF PAIN MANY THE UPCOMING RENDITION OF NATIONAL CLASSIFICATION OF DISEASES BY WHO. AND WE HAVE SUCCEEDED. WE PUB PUBLISHED ON THIS EFFORT ONE AND A HALF YEARS AGO, BEGINNING OF LAST YEAR. SERIES OF PAPERS. ONE OF THE ACCOMPLISHMENTS WAS TO INCLUDE OPERATIONAL DEFINITION OF PAIN SEVERITY. THAT COMBINES PAIN INTENSITY RATING BUT ALSO RATING FOR PAIN DISTRESS AND APPEARANCE IN DAILY ACTIVITIES. IN THE ICUD 11 YOU HAVE THE CHANCE TO USE RATINGS SEVERITY RATING AS EXTENSIONS CODES THAT FOLLOW DISEASE CLASSIFICATION. THAT'S ONE STEP FORWARD, ACTION IS INITIATIVE THAT HAS PROPOSED SIMILAR CONSTRUCT AND I THINK THAT'S DEFINITELY SOMETHING WE CAN CONSIDER ONE OF THE INTERESTING OUTCOME MEASURES IN FORTHCOMING PAIN TRIALS. HOW CAN WE TARGET THE RIGHT DRUG TO THE RIGHT PATIENT? ON THIS SLIDE I SHOW YOU EXAMPLES OF TWO EMPIRICAL APPROACHES NOT SO UNCOMMON. FIRST IS CALLED ENRICH ENROLLMENT FOR RANDOMIZED WALL, IT HIGHLIGHTS TRIAL CONDUCTED WITH ONE OF BIOGEN'S COMPOUNDS (INDISCERNIBLE) WHAT THE INVESTIGATORS DID HERE WAS TO START TREATMENT IN OPEN LABEL FASHION WITH IDENTIFY TRUE RESPONDERS. IT TOOK THOSE RANDOMIZED THEM IN DOUBLE BLIND CONTROL STAGE OF THIS TRIAL TO COMPARE EFFICACY AGAINST PLACEBO. THE TRIAL DESIGN ON THE RIGHT HAND COMES FROM A DIFFERENT ANGLE, IT'S NOT DESIGNED TO P CREASE NUMBER OF RESPONDERS IT WANT TO EXCLUDE FALSE RESPONDER. SO PARALLEL DESIGN WAS INVENTED AT MASSACHUSETTS GENERAL HOSPITAL, BOSTON. AND IT ALSO HAS TWO STAGES. THE FIRST STAGE YOU IDENTIFY PARTICIPANTS WHO RESPOND TO PLACEBO AND EXCLUDE THOSE FROM FOLLOWING DATA ANALYSIS FOR THE SECOND STAGE WHICH RANDOMIZES PLACEBO, NON-RESPONDERS TO AN ARM WITH ACTIVE TREATMENT AND COMPARISON ARM WITH PLACEBO. THE PURPOSE IS TO SELECT PATIENTS WITH RELATIVELY SMALL SAMPLE SIZES TO DETERMINE WHETHER YOU HAVE A GOOD -- YOU WANT TO INCREASE SIGNAL TO PLACEBO RATE, AND THIS IS TREATMENT FOR PROOF OF CONCEPT IN PHASE 2. I THINK I WILL BE MORE DIFFICULT TOTY FEND A RILE DESIGN IN PHASE 3 WHERE YOU WANTED TO LEARN HOW WELL YOUR DRUG WOULD WORK IN THE GENERAL POPULATION. THERE ARE OTHER APPROACHES THAT ARE MORE CONCEPTUALLY DRIVEN WITH THE UNDERSTANDING THAT WE MAY HAVE INSIGHT INTO PAIN MECHANISMS OR AT LEAST UNDERSTANDING PAIN MECHANISMS RELATES TO THE PAIN PHENOTYPE THAT WE CAN ASSESS IN OUR PATIENTS. THE IDEA HERE IS THAT YOU RUN YOUR TRIAL YOU HAVE STANDARDIZED PROTOCOL TO DETERMINE PAIN RELATED SYMPTOMS AND SIGNS THAT DEFINE THE PATIENT PHENOTYPE AND YOU SEE WHICH SCIENCE CORRELATE WITH TREATMENT SUCCESS. THEN YOU RUN A FOLLOW-UP TRIAL WHERE YOU CONFIRM THIS CORRELATION IF TRUE YOU CAN YOU CAN USE THAT TO INSTRUCT HOW IT SHOULD BE BEST USED IN A PATIENT POPULATION, YOU CAN IDENTIFY MOST LIKELY RESPOND TO THIS. YOU CAN ALSO IMPLEMENT PROTOCOL PROVOCATIVE TESTS, FOR -- WHO WAS HERE PRESENTING YESTERDAY, HAS PUBLISHED ONE TRIAL THAT I PINED INTERESTING WHERE SHE DETERMINED THAT PATIENTS WHO PROVE TO BE HYPOAL JEEZIC IN THE CAP SAY SIN SPACE, TO CHON DEAN IN ORAL POPULATION IN THIS TRIAL. QUANTITATIVE SENSORY TESTING IS BASICALLY A VERY SOPHISTICATED WAY TO DETERMINE THE PHENOTYPE OF YOUR PATIENT. SO FIT IN TOP ROW EXAMPLE ON PREVIOUS SLIDE. ET LET'S DETERMINE WHICH TYPE OF PATIENT IS RESPONDING BEST TO TREATMENT. ROY HAS INTRODUCED THE PROTOCOL FOR THIS PAIN SENSITIVITY ASSESS MENT, WELL CHARACTERIZED HIGHLY STANDARDIZED INFORMATION ABOUT THOUSANDS OF PATIENTS. COLLEAGUES WHO INVENTED THIS PROTOCOL HAVE IDENTIFIED THREE MAJOR PHENOTYPES IN THE REALM OF NEUROPATHIC PAIN. HAIR TERM SENSORY LOSS THERMO HYPOAL JEEZIA OR MECHANICAL HYPERALGESIA. THE PROTOCOL IS 60% SENSITIVITY AND SPECIFICITY TO DIFFERENTIATE THESE PHENOTYPES. I THINK THAT'S WHAT YOU PROBABLY CAN EXPECT WITH SUCH A CLINICAL ASSESSMENT METHOD. BUT IT'S NOT REALLY HIGH. IT HAS PRACTICAL IMPLICATIONS. SO I THINK STANDARD ASSUMPTION IN ANALGESIC TRIAL IS THAT WE HAVE AN AFFECT OF -- IF I WOULD TRY TO STEER MY TREATMENT OR TEST MY TREATMENT IN A POPULATION THAT HAS MECHANICAL HYPERALGESIA BECAUSE I THINK IT'S A GOOD TREATMENT FOR THIS PHENOMENON LIKE ALLODYNIA, I WOULD HAVE TO SAY AT LEAST 171 PATIENTS TO IDENTIFY THAT PARTICULAR PHENOTYPE. THAT'S ONLY IF I ALLOW PATIENTS TO PROBABLYISTICLY BELONG TO MORE THAN ONE PHENOTYPE. SECOND ROW. THE FIRST ROW IS THE NUMBER THAT I WOULD NEED TO SCREEN IF I SAY ONLY ONE PHENOTYPE PATIENT. HERE WE ARE TALKING ABOUT MORE THAN 600 PATIENTS. THIS IS ONE SAMPLE, IF I HAVE A TWO ARM TRIAL I'M IN WITH ABOUT 340 PATIENTS. I CAN TELL YOU THIS WILL NOT HAPPEN. IT'S TOO EXPENSIVE, THIS IS NOT WHAT WE CAN INVEST IN PHASE 2 TRIAL. ON TOP YOU HAVE TO INVESTIGATORS ACROSS MULTIPLE SITES THAT THEY UNIFORMLY APPLY THIS ASSESSMENT, GREAT SOME VARIABILITY YOU HAVE TO CONTROL FOR THAT. THAT'S -- IT'S UNREALISTIC. I THINK QUANTITATIVE SENSORY TESTING OR THIS TYPE OF PROFILING IS VERY GOOD AS AN EXPLORETORY OUTCOME MEASURE LEARN WHAT OUR DRUGS DO, WE CANNOT INVOLVE THEM IN PRIMARY OR SECONDARY CONDITIONS. THERE'S ANOTHER CAVEAT QUANTITATIVE SENSORY TESTING APPARENTLY IS VERY -- HAS LOW SENSITIVITY TO DIFFERENTIATE BETWEEN PAINLESS AND PAINFUL NEUROPATHY. THE FIRST TWO PANELS HERE FROM PAIN MURR ROUP THINK IS ONE OF THE BEST WE HAVE MANY DIABETIC NEUROPATHY, ENROLLED 111 PATIENTS WITH PAINFUL DIABETIC NEUROPATHY AND 80 PATIENTS WITH PAINLESS. THESE PATIENTS WERE EXPOSED TO WHOLE BATTERY OF ASSESSMENTS INCLUDING QUANTITATIVE SENSORY TESTING BASED ON THIS GERMAN PROTOCOL WHICH I THINK SETS THE GOLD STANDARD IN THE FIELD. WHAT THE VISITORS FOUND IS THEY CAN DIFFERENTIATE BETWEEN PAINLESS AND PAINFUL NEUROPATHY EYE CHRONICALLY BETTER THAN THOSE DETECTION THRESHOLDS, W -- SPARING THE DETAILS. THEN IN ACTUAL PAIN MEASURES. THE ONLY ONE THAT WAS SIGNIFICANT WAS TO -- HEAT PAIN THRESHOLD HPT. AND I HAVE TO SAY THAT I SAW THESE DATA BEFORE THE DIFFERENTIATION BETWEEN MILD AND MODERATE TO SEVERE PAIN AND THERE WAS NO DIFFERENCE. IT WAS A POSTER PRESENTATION AT ONE OF THE ISP MEETINGS, LOOK AT THE DIFFERENCES, THEY ARE PAIRLY SMALL, THE VARIABILITY IS HIGH. WITH SENSORY TESTING HAS BEEN FOUND IN OTHER MURR ROUP THINKS LIKE THIS EXAMPLE, WITH PATIENTS WHO SUFFER FROMLY PRO SCHISM IF I HAVE A TOOL THAT DOESN'T DISTINGUISH BETWEEN PAINLESS AND PAINFUL NEUROPATHY YOU CANNOT INVEST MILLIONS OF DOLLARS INTO USING THIS TOOL FOR PRIMARY OR SECONDARY OUTCOMETS. EXPLORATORY OUTCOME MEASURE, INFORMATIVE, BUT AT THE MOMENT THAT'S ABOUT IT. ON A BRIGHTER NOTE, WITH MY PROGRESS WITH DISEASE MODIFYING TREATMENTS, FIRST EXAMPLE HERE IS AGAIN FROM THIS TRIAL DRUGS IN NEURAL GEEIA, THE SECOND PART OF THE TRIAL WAS THE RANDOMIZED DOUBLE BLIND TESTING. WHAT WE HAVE SHOWN HERE DEPICT MISDEMEANOR THE FIRST PANEL IS THAT WE CAN REDUCE THE FREQUENCY OF NEUROLOGIC ATTACKS ABOUT -- BY 60% COMPARED TO 20 TO 25% PLACEBO GROUP. SIMILAR EXCITING RESULTS ARE REPORTED FROM MIGRAINE TRIALS HAS BEEN SHOWN TO REDUCE THE NUMBER OF MIGRAINES IN THESE PATIENTS QUITE SIGNIFICANTLY. IF YOU HAVE A SUSTAINED TREATMENT SUCCESS, LIKE WITH THESE ANTIBODIES TO TARGET CT (INAUDIBLE) RECEPTOR YOU CAN TALK ABOUT PAIN PREVENTION. THE EXAMPLE OF MIGRAINE, I WOULD CLASSIFY AS SECONDARY PREVENTION. WE HAVE NOW DATA FOR OVER ONE YEAR. THESE PATIENTS HAVE MAINTAINED REDUCTION IN MIGRAINE DAYS AND NUMBER OF PATIENTS THAT ACHIEVE MORE THAN 50% REDUCTION IS REMARKABLE. 50% THAT IS GREAT. WE ALSO HAVE ANOTHER EXAMPLE THAT I WOULD CONSIDER PRIMARY PREVENTION OF PAIN THOSE ARE TWO VACCINES HA WE HAVE FOR THE VIRUS, WE RETUESDAY THE I'M SORRY TENSE OF -- THEY ALSO REDUCE POST HER PETTIC NEURAL GEEIA, THAT'S PHENOMENON. THAT'S REALLY GOOD. PHENOMENAL. WE CAN THINK ABOUT PREVENTION AS TREATMENT OBJECTIVES WHEN WE HAVE EPISODIC PAIN OR DEFINED EVENT THAT TRIGGERS RISK OF DEVELOPING PAIN SUCH AS -- BUT I WOULD PUT INTO THIS CATEGORY OF INJURIES OR NEUROTOXIC CHEMOTHERAPY. A FEW WORDS ABOUT BIOMARKERS. WE TOUCHED UPON FIRST STATEMENT FROM GUIDANCE THIS POINT IN TIME HAS BEEN WITHDRAWN AMALL JEEZICS INDICATIONS BY FDA PAIN INTENSITY IS FUNDAMENTAL CLINICAL OUTCOME MEASURE THAT DEFINES THE EFFICACY OF AMALL JEEZIA. THAT SHOULDN'T CHANGE. WHEN I THINK ABOUT BIOMARKERS IN DESIGN OF MY TRIALS, I DON'T WANT TO REPLACE THE INTENSITY RATING. I LOOK MORE BIOMARKERS THAT FALL INTO A DEFINES CATEGORIES LIKE DIAGNOSTIC PROGNOSTIC OR PREDICTIVE MARKERS. I WOULD LIKE -- WE CAN USE BIOMARKERS VERY EFFECTIVELY IN PHARMACOKINETIC STUDIES AND FOR SAFETY. IT'S IMPORTANT TO THINK ABOUT THE CONTEXT WHICH YOU WANT TO USE YOUR BIOMARKER, OR BIOMARKER SHOULD HELP YOU ANSWER AND YOU SHOULD TAKE THE RIGHT ONE THAT HAS CONSTRUCT VALIDITY. YOU HAVE TO REFLECT ABOUT THE BENEFITS TO THE PATIENTS AND THE RISKS BENEFITS ARE MY TREATMENT DEVELOPMENT IS MORE EFFICIENT WHAT WE ACCELERATED IN THE BEST CASE, THE RISKS ARE THAT THERE IS DISCREPANCY, I MAY PRODUCE BEAUTIFUL MRI, PATIENT IS STILL IN PAIN, YOU IMMEDIATE TO THINK ABOUT THESE QUESTIONS BECAUSE THEY HAVE ETHICAL, DEVELOPMENT CONSEQUENCE. MARY ANN MENTIONED THAT WE HAVE A WORKSHOP IN I THINK IT WAS NOVEMBER 2018. WHICH WAS EXCELLENT. LOTS OF EXTRAS -- EXPERTS FROM ACADEMIA, REPRESENT THE INDUSTRY, FDA, NIH, WE DISCUSSED BIOMARKERS IN PAIN FIELD. AND THERE'S A WHOLE LIST OF POSSIBLE BIOMARKERS THAT WE CAN USE IN DRUG DEVELOPMENT. THOSE PAPERS NOW REVIEW, HOPEFULLY WE'LL HAVE IT OUT SOON. I HIGHLIGHT TWO EXAMPLES THAT I FIND VERY IMPRESSIVE, ONE IS MEASUREMENT OF CTRP IN THE VEIN OF MIGRAINE PATIENTS THAT HELPED TO DEVELOP NEW EFFECTIVE TREATMENTS FOR THIS PARTICULAR DISEASE. ANOTHER EXAMPLE IS THE FLAIR RESPONSE ON THE FOUR ARM, WE INJECT IRRITANT YOU MEASURE THE INCREASE IN INFLAMMATION THIS PROVOKES. THAT IS A USEFUL TOOL FOR EXAMPLE OF RECEPTOR ANTAGONIST TRIP A 1 RECEPTOR ANTAGONIST, ESPECIALLY THE LATTER, RODENT MODELS WOULDN'T HELP THAT MUCH. I'M ALSO EXCITED ABOUT CUTTING EDGE DEVELOPMENTS THAT WE CAN ISOLATE, NOCICEPTIVE NEURONS NOW FROM GUT BIOPSIES OR POST MODEM SAMPLES, WE HAVE PROTOCOLS TO DEVELOP SENSORY NEURONS INCLUDING NOCICEPTIVE NEURONS FROM INDUCED PLURIPOTENT STEM CELLS, APPLIED AS DISEASE MODELS, INCLUDING FOR PAINFUL AT THIS ORDERS LIKE INHERITED (INAUDIBLE) I THINK THEY WILL BE VERY GOOD-BYE MARKERS, SO BIOMARKER TOOLS GOING FORWARD. NEVERTHELESS WE STILL HAVE LONG WAY TO TWO BEFORE WE CAN REALLY REVAMP TRIAL DESIGN AND PAIN. WE SHOULD TAKE A LOOK AT OTHER FIELDS TO DEFINE OUR CURRENT POSITION. I LIKE TO TWO TO THE ONCOLOGY FIELD BECAUSE THEY HAVE -- THERE'S BEEN SO MUCH PROGRESS. THIS DIAGRAM SHOWS THE DESIGN OF A TRIAL THAT IS CALLED I SPY TOO. IT WAS DESIGNED FOR PATIENTS WITH ADVANCED BREAST CANCER SO THAT UP TO FIVE TREATMENTS COULD BE TESTED SIMULTANEOUSLY. IN A VERY EFFICIENT WAY. THE BIOMARKERS THAT THESE INVESTIGATORS USED INCLUDED MRI OF THE TUMOR SITES,S TO DETERMINE TUMOR SIZE, THEN BIOPSIES BEFORE AND AFTER TREATMENT. BUT THEY ALSO IMPLEMENTED ADAPTIVE TRIAL DESIGN, A PATIENT FORMULA, THAT WOULD STEER PATIENTS DURING THE TRIAL THROUGH EFFICACY ANALYSIS TO THE TREATMENT COMBINATION THAT WOULD ICKILY BE SUCCESSFUL. WITH THAT DESIGN THEY WERE ABLE TO RETUESDAY THE NUMBER OF PATIENTS TO DECIDE THAT THE TRIAL TREATMENT COMBINATION IS INEFFECTIVE TO ABOUT 60. AND NEEDED ONLY UP TO 120 PATIENTS TO DECIDE TREATMENT COMBINATION IS SUCCESSFUL. THAT IS GREAT. WITHIN SIX YEARS TO THESE TWO BACK TO BACK PUBLICATION IN JOURNAL OF MEDICINE. THAT IS SOMETHING WE SHOULD ASPIRE TO. WE ARE NOT THERE YET. SO I'M OVERALL OPTIMISTIC NEW OUTCOME MEASURES IN PAIN WILL IMPROVE TREATMENT DEVELOPMENT, THESE BIOMARKERS HAVE TO BE VALID, HAVE TO BE ACCURATE, RELIABLE, ELIZABETH BROUGHT UP GENERALIZABILITY AND I PUT IT ON MY SLIDE THAT'S IMPORTAT UNLESS WE WANT TO STEER OUR TREATMENT TO A PARTICULAR SUB POPULATION OF PATIENTS. SENSITIVITY TO CHANGE IS OBVIOUS CRITERIA, ALSO CONSIDER REGULATORY IMPACT IMPLEMENTATION OF ALTERNATIVE OUTCOME MEASURES HAS. WE MAY REDUCE TARGET POPULATION FOR WHICH THIS TREATMENT IS DEVELOPED. THAT'S SOMETHING CERTAINLY IMPORTANT TO CONSIDER. FROM I WOULD HOPE THE UPCOMING VERSION OF THE SRI GUIDANCE FOR ANALGESIC INDICATIONS INCLUDS A DISCUSSION OF THESE NEW OUTCOME ISSUES IN PARTICULAR BIOMARKERS WHAT WOULD BE CONSEQUENCES FOR APPROVAL OF TREATMENT. THAT WILL BE VERY HELPFUL. THANK YOU. [APPLAUSE] IS >> THANK YOU VERY MUCH FOR THAT THOUGHT PROVOKING PRESENTATION. WE'LL TAKE A 60 SECOND BREAK WHILE WE GET DR. BORSUK ON THE LINE WHO WILL BE PRESENTING REMOTELY. IN THE INTERIM I WILL INTRODUCE DR. BORSUK -- CHALLENGES ON MEASURING THE BRAIN STATE. DR. BORSUK TRAINED IN NEUROLOGY, PAIN MEDICINE AN NEUROBIOLOGY, HE'S CURRENTLY DIRECTOR OF THE CENTER FOR PAIN AND BRAIN WHICH ENCOMPASSES CHILDREN'S HOSPITAL, MASS GENERAL AND MCCLAIN HOSPITAL, HE IS PROFESSOR AT HARVARD AND HOLDS THE MAY DAY CHAIR AND SYSTEMS NEUROSCIENCE. THANK YOU VERY MUCH AND WELCOME. CAN YOU HEAR US? >> HELLO. >> THERE YOU ARE. THANK YOU. >> HELLO. >> WE CAN HEAR YOU. >> A LOT OF ECHO. >> CAN YOU HEAR US? >> YES. >> GREAT. THANK YOU. WE ARE READY FOR YOUR PRESENTATION. THANK YOU. >> OKAY. SO THANKS FOR THE INVITE. I APOLOGIZE FOR ATTENDING -- SENDING EMAIL OUT TO EVERYONE WHEN IT SHOULD HAVE JUST GONE TO LIZ. SLIDE 1 WHICH IS THE HEADING OF TALK HOPEFULLY REFLECTS THE OVERALL THEME THAT I'M PLANNING TO TRY AND COMMUNICATE, THAT IS WHAT REALLY PRODUCES PATIENTS THAT ARE RESISTANT TO PAIN CHRONIC IN THOSE THAT ARE NOT. THIS THEME IN THE SECOND SLIDE IS KIND OF LIKE A SPIN TALK, A SPIN TOP THAT IS STABLE FORM SPINNING PERPENDICULARLY AND RESISTANT TO FALLING BASED ON PROCESSES THAT CONTRIBUTE TO THAT STABILITY. IF YOU -- FALL AWAY OR ADD THINGS TO THE SIZE OF IT, IT WILL BECOME WOBBLY AND FALL DOWN TO ME THESE ARE ISSUE US WE FACE IN TERMS OF TRYING TO DEFINE BIOMARKERS FOR CHRONIC PAIN. THE NEXT SLIDE, NUMBER THREE, ONE OF TWO CLINICAL EXAMPLES WHERE THESE CHALLENGES ARE SUMMARIZED IN THE SLIDE WHICH I PURPOSEFULLY COMPLICATED, THE ISSUE IS COMPLICATED, BASICALLY MIGRAINE LIKE OTHER PAIN CONDITIONS IS BEHAVIORALLY VERY WELL DEFINED FROM INTERICTAL AND POSTICTAL AND QUANTIFICATION. AND YET EVEN WITH THESE DOMAINS, THE MIGRAINE PHENOTYPE IS VARIED. AND SO WHEN WE ACTUALLY TRY TO CAPTURE BRAIN METRICS OR OTHER METRICS IT DOES VARY ACROSS TIME EVEN DURING THE PRE AND ICTAL PERIODS. THE OTHER EXAMPLE,S SURGERY, IN THE NEXT SLIDE, THAT BASICALLY THE SURGICAL PROCESS FOR MOST PATIENTS IS THE SAME BUT PRE-SURGICAL CONDITION DEFINES IN WAYSES THAT ARE NOT FULLY UNDERSTOOD THEIR POST SURGICAL PROBLEMS FOR -- FROM BEHAVIORAL DISORDERS IN AUTISTIC CHILDREN UNDERGOING ANESTHESIA FOR EXAMPLE, OR CHRONIC NEUROPATHIC PAIN ALSO PRESENT PATIENTS MAY HAVE. SO PART OF THE ISSUE IS WE DON'T KNOW WHAT WE ARE TRYING TO MEASURE OR WE CAN'T MEASURE IT. TO THIS THEME A GROUP OF US LISTED ON THE RIGHT AND SUPPORTED BY TWO GRANTS SPECTROSCOPY TO EVALUATE NOCICEPTIVE SLASH PAIN PROCESSES UNDER ANESTHESIA, ON THE LEFT YOU SEE LYMPH NODE SIGNAL WHERE ARROWS SHOW EVENTS SUCH AS PULLING CUTTING TEARING OR WHATEVER SURGEONS DO WITH THE SIGNAL THAT IS DETAILED IN PAPERS WE PRESENTED OR PUBLISHED THAT REPRESENT A NOCICEPTIVE EVOKED CHANGE SHOWN IN HEALTHY SUBJECTS. HOWEVER, WHEN THERE'S COMPLETE NOCICEPTIVE BLOCKADE, THESE SIGNALS REMAIN STABLE. SO ONE OF THE THEMES DOES THIS PROCESS AS SEEN MT. TOP OF THE TRIGGER CONTRIBUTE TO CENTRALIZATION OR SENSITIZATION THAT THEN MAKES THERAPEUTIC ISSUES AFTER SURGERY BEYOND MORE DIFFICULT. SO IN SLIDE 6 SO HOW DOES CHAOS EVOLVE, THIS -- ALTHOUGH THIS FIGURE WAS USED IN A PAPER IN NEURON, IN TERMS OF COMMON BRAIN NECK MECHANISMS OF PAIN AND ADDICTION, I THINK IT'S SOMATICALLY SUMS UP WHAT I UNDERSTAND MUCH OF THIS MEETING IS ABOUT. AND THAT RELATES TO IN THE JUST INITIATING EVENT OF PAIN WHETHER SURGICAL OR OTHER, WHERE ALL THESE PROCESSES SUCH AS DESCENDING MODULATION MAYBE ALTERED BUT WHATEVER HAPPENS EMOTIONS COGNITION, PAIN BEHAVIOR, INTERPERSONAL INTERACTIONS IN VARIOUS OTHER PROCESSES, AS NOTED SUCH AS PRE-OCCUPATION AND COMPULSIVITY ADDS TO THIS CIRCLE OF EVENTS THAT SEEM TO AMPLIFY INITIALLY NOCICEPTIVE PROCESS. IN THE NEXT SLIDE THIS INITIATION FOR ME AT LEAST IS REALLY BEEN CAPTURED IN THE CLINICAL SYNDROME WE CALL COMPLEX REGIONAL PAIN SYNDROME, WHERE A SIMPLE INJURY LEADS TO NUMBER OF PROCESSES SUMMARIZED HERE FROM SENSORY SPREAD BEYOND THE AREA OF MAYBE CHANGES IN PERCEPTION THAT MAY BE (LOST AUDIO) AS WELL AS COGNITIVE CHANGES. SO SOMETHING IN THE PERIPHERY ELICITS THESE AND MANY THIS SYNDROME YOU CAN SEE HEM BECAUSE THEY -- FOR OTHER PAIN SYNDROMES WE ARE PROBABLY NOT DOING A GOOD JOB IN TRYING TO DEFINE THESE AS WELL. THE NOTION ONCE YOU HAVE AN INJURY OR A DISEASE OR PAIN THAT AFFECTS MULTIPLE AREAS OF THE BRAIN, IT IS A BIT OF A DIFFICULT CONCEPT BECAUSE MANY OF US IN IMAGING WILL OVERLOOK NETWORK CHANGES VERSUS CHANGES IN ONE AREA SUCH AS -- OR THE INCUMBENTS OR THE AMYGDALA AND USE IT TO DEFINE PROCESSES THAT RELATE TO IT SUCH AS ANXIETY OR FEAR THAT MAY NOT BE LOOKING AT THE OTHER PROCESSES THAT CONTRIBUTE TO DISPLACING THE (INDISCERNIBLE) IN THE NEXT SLIDE WHICH IS HEADED CONCEPT 3 FAILINGS SYSTEMS, WHAT WE TRIED TO DO HERE IS LOOK AT TWO TWO PROCESSES REWARD DEFICIENCY AND REWARD IN PAIN QUANTIFICATION. I THINK THEMEICLY OUTSIDE OF THIS CHANGE TOP FROM HEALTHY TO CHRONIC PAIN STATE IN TERMS OF PAIN QUANTIFYCATION, WE SUGGEST THAT THERE MAYBE TWO MAJOR SYSTEMS DRIVING THESE CHANGES INCLUDING REWARD AND MOTIVATION IN THE GRAY TRIANGLE LEADING TO A REWARD DEFICIENCY STATE. AND THEN STRESS CENTERS ON THE RIGHT WE HAVE THIS COURT SOLVE AND OTHER STRESS HORMONES RELEASED THAT MAY CONTRIBUTE TO PROCESSES SUCH AS FEAR AND ANXIETY. SO THIS COMBINED PROCESS, AT LEAST AS A MODEL MAY SIGNIFICANTLY CONTRIBUTE IN ALTERED ALLO STATIC STATE TO ALLO STATIC LOAD FAILING SYSTEMS AND INCREASE SEVERITY OF THE PROBLEM. SO GETTING BACK IN SLIDE -- NEXT SLIDE MEASURING COMPLEX PROCESSES IS DIFFICULT, BASICALLY IF WE LOOK AT THESE STIMULI WHETHER THEY ARE NOCICEPTIVE OR OTHER STIMULI, EFFECTING WHAT YOU SEE IN THE MIDDLE OF THE GRAY SQUARE, LOOKING AT THIS DETECTION SYSTEM THERE'S A BALANCE IN ADAPTATION THAT LEADS TO RECOVERY AND STABILITY OR A ABNORMALITY THAT INVOLVES EMOTIONS BEHAVIORS AND COGNITIVE CHANGES OUTSIDE OF ACCEPTSRY CHANGES THAT LEAD TO THIS CHAOTIC STATE. SO I THOUGHT I WOULD GIVE YOU SOME EXAMPLES OF WORK THAT HAS COME FROM OUR GROUP, MANY GROUPS CENTING TO THIS THEME BUT HERE WE GO. FIRST RELATES TO A PSYCHO-- SHOULD BE PHYSIOPSYCHOLOGICAL STATE, AND THIS WAS ASSOCIATED IN OUR LAB WITH NORA SIGH MN WHO JOINED US AS A K MENTEE AND NOW GONE ON TO STANFORD BRILLIANTLY. ONE OF THE THEMES THAT CAME UP IS THIS NOTION OF PATIENTS IN THIS CASE COMPLEX REGIONAL PAIN SYNDROME PATIENT WHOSE ARE NONRESPONDERS, NON-RESPONDERS IN THIS CASE TO A CHRONIC REHAB PROGRAM. AND THESE CHANGES ARE VERY DIFFERENT ACROSS THESE PATIENTS IN TERMS OF HOW THE INCUMBENTS IN OTHER AREAS -- IN OTHER PARTS OF THE BRAIN REACT. THE THEME IS, WHAT IS IT ABOUT THE NON-RESPONDERS WHERE THEIR BRAINS BECOME STUCK? IN THE BOTTOM RIGHT HAND CORNER YOU CAN IF INTERESTED READ MORE ABOUT IT. WHERE WE TALK ABOUT WHEN PAIN GETS STUCK IN TERMS OF RESISTANCE TO TREATMENT. THE SECOND THEME, THIS IS WORK THAT WE DO WITH ROY FREEMAN AND GAIL ADLER, THE QUESTION IS HOW DOES STRESS IMPACT ON BRAIN SYSTEMS ACUTELY AND CHRONICALLY AND CLEARLY THERE ARE MANY DISEASES THAT ARE AFFECTED BY THIS INCLUDING CHRONIC PAIN THIS WORK IS RECENTLY FUNDED AND SUPPORTED BY NINDS. AN EXAMPLE IS GIVEN BELOW FUNCTIONAL CONNECTIVITY WITH HYPOTHALAMUS GLUCOSE HYPOGLYCEMIC STRESSOR WHERE THERE ARE SIGNIFICANT CHANGES RELATIVE TO PRE-STATE BEFORE THIS HYPOGLYCEMIC (INAUDIBLE) THE THIRD ONE REMITS TO THE STUDY THAT'S -- SCOTT HOLMES IN MY GROUP WHERE WE TRIED TO INTEGRATE BRAIN SAL VARY PERIPHERAL NERVE WHERE WE CAN GET METRICS OF CHANGES IN THE NERVE FOLLOWING PERIPHERAL NERVE INJURY AS WELL AS CLINICAL MEASURES AND TRY TO INTEGRATE THESE, I THINK THIS THEME IS BECOMING STANDARD ACROSS THE FIELD WORKS SUPPORTED BY THE CHILDREN -- CHILD INSTITUTE. THE PAPER AT BOTTOM SUMMARIZES WILL GIVE YOU MORE DETAIL ABOUT THIS INCLUDING THE IMMUNOPROFILES AND WHAT WHAT HAVE YOU. WHAT'S SO INTERESTING FOR ME ABOUT THIS IS HOW CHANGES IN A PARTICULAR IMMUNOLOGICAL STATE CORRELATE WITH NERVE STATES AS WELL AS BRAIN STATES IN TERMS OF EVEN THEMES OF DEPRESSION AND SO FORTH. I THINK THIS INTEGRATIVE APPROACH HAS A LOT GOING FOR IT. SOMEHOW I MISSED OUT ON A SLIDE H. ANOTHER HEME THAT IS MUCH HARDER TO CAPTURE IS OUR ENDOGENOUS RECEPTOR STATES. WORK THAT INITIALLY WAS INITIATED WITH ONE OF THE PRESENTERS CLAS LINNMAN AND SUBSEQUENTLY TANKEN ON TO WORK WITH JACOB HOOKER TO LOOK AT CHANGES IN MIGRAINE -- IN OPIOID BINDING IN HEALTHY VERSUS MIGRAINE PATIENTS, WE HAVE THIS LITTLE MODEL ON THE LEFT BASICALLY LOOKING AT VARIOUS ISSUES INCLUDING ALLO STATIC LOAD, PAIN CONTINUUM IN MIGRAINE I.E. EPISODIC LOW FREQUENCY VERSUS EPISODIC HIGH FREQUENCY LOOKING AT PARTICULAR RECEPTOR FUNCTION AND SO FORTH. ON THE RIGHT THESE BRAIN IMAGES SHOW SEX DIFFERENCES FOR OPIOID BINDING POTENTIAL IN THE VENTRAL TEGUMENTAL AREA IN EPISODIC MIGRAINE DIFFERENCES ARE BETWEEN MEN AND WOMAN WHERE THERE IS INCREASED BINDING IN WOMAN COMPARED WITH MEN. LOOKING AT FREQUENCY OF MIGRAINE YOU SEE INCREASED FREQUENCY, INCREASED BINDING IN PATIENTS WHO HAVE NO FREQUENCY MIGRAINE SO BASICALLY THESE DOMAINS OF OPIOID RECEPTORS CERTAINLY CONTRIBUTE TO FUNCTION IN WAYS THAT CLEARLY NEED TO BE INTEGRATED. SECOND TO LAST IS THE WHAT WE CALL IS CYCLE CLINICAL STAGE WHERE SOMEONE MAY HAVE MILD OR MODERATE OR SEVERE CONDITIONS INCLUDING POST TRAUMATIC STRESS DISORDER AND THIS WORK DONE BY IGOR TOOK PTSD PATIENTS AND SHOW THEIR HYPERSENSITIVITY TO EVEN MILD THERMAL STIMULI OR AND DIVERSE PICTURES, AGAIN MAKING THE POINT WHEN WE SEE A PAIN PATIENT HOW DO WE KNOW HOW MANY OF THESE DOMAINS ARE CUMULATIVE IN TERMS OF THEIR PRESENTATION IN THE CLAY IN THIS CASE. JUST TO GIVE AN EXAMPLE OF HOW ONE CAN BEGIN TO TEASE THIS OUTGOING BACK TO THE WORK THAT SCOTT HOLMES HAS DONE IS BASICALLY IF YOU HAVE A NERVE INJURY, IN THIS CASE AN ANKLE SPRAIN, AN ANKLE SPRAIN EXPOSING NEUROPATHIC PAIN THERE ARE CHANGES THAT OCCUR IN TERMS OF NO CHANGES AS MEASURED BY DTI WITH SIGNIFICANT CHANGES ALL WAY UP THE SCIATIC NERVE FROM THIS CHANGE. THESE CHANGES ARE CLINICALLY EVALUATED BUT DTI MEASURES MAY PERSIST AS CORRELATE OF THE ONGOING THING. AND WE ALSO CAN MEASURE THESE CHANGES IN PERIPHERAL CYTOKINE MEASURES. THE BOTTOM PINK BLUE GRAPH SHOWS BIOLOGICAL BEHAVIORAL MARKERS AND SHOWS INTEGRATED CROSS MODAL ANALYSIS FOR ALL THESE MEASURES WHERE WE CAN BEGIN TO SEGREGATE HEALTHY CONTROLS FROM THOSE PATIENTS WITH ANGLE SPRAIN AT BOTH POPULATION AND NOT SHOWN HERE AT AN INDIVIDUAL LEVEL. SO THE THEME OF THE SPINNING TOP AND ITS MULTIPLE PROCESSES THAT KEEP IT STABLE HAS TO BE LOOKED AT IN TERMS OF MODEL AS SHOWN HERE IN TERMS OF REGULATORS THAT HAD MONITORED PARAMETERS THAT WE CAN DEFINE AND EACH COLOR IS DETAILED ON THE RIGHT IN THE BALLOON, FOR REGULATORS THERE ARE REGIONS OF THE BRAIN OR NEUROCHEMICAL FOR THE ADEN STAT MAYBE ANATOMICAL REGION SPECIFICALLY SUCH AS THE ACUMBENS OR DOPAMINE FOR EFFECTERS WITHIN AND BETWEEN SYSTEMS AS NOTED AND MONITORED PARAMETERS INCLUDE ACCUMBENS INCLUDE EMOTIONS AN MOTIVATIONS. AT THE END OF THIS -- THE THEME OF ALLO STATIC LOAD IN TERMS OF HOW FAILING SYSTEM BECOMES FAILING IN ITSELF CONTRIBUTES FURTHER TO THIS STATE. SO TO END I WANTED TO MENTION A GREAT FRIEND AND MENTOR AND SCIENTIST WHO DIED RECENTLY BRUCE MCCAIN WHO I HAD THE FORTUNE WHO WORK WITH AND HE HAD REALLY HELPED ME THINK ABOUT PAIN IN A COMPLETELY DIFFERENT WAY. THERE ARE MULTIPLE CONTRIBUTORS FROM BOSTON CHILDREN ISRAEL MCCLAIN MASSACHUSETTS GENERAL MIT AND MCCLAIN AND SOME OF THEM I LISTED AS I WENT THROUGH THE TALK. I HOPE THIS IS SOME THEMEIC INTEREST TO THIS MEETING. IF NOT I ASSUME THIS WILL JUST BE DELETED. THANK YOU. [APPLAUSE] >> DAVID THIS IS WENDY, I WANT TO SAY THANK YOU FOR DOING THIS REMOTELY. WE KNOW THIS ISN'T EASY AND HOPE YOU FEEL BETTER. THANK YOU. >> THANKS. >> THANK YOU VERY MUCH. VERY SIMILAR KNOLL WORK MEASURING BRAIN STATES. >> PLEASE STAY ON IF YOU WOULD LIKE TO PARTICIPATE IN THE PANEL DISCUSSION AFTER THE NEXT PRESENTATION. JUST PUT YOURSELF ON MUTE UNTIL THEN. >> NEXT PRESENTATION IS DR. BILL RILEY ON BEHALF OF DR. ARTHUR STONE. A MOMENTARY MEASUREMENT PERSPECTIVE TO PAIN INTENSITY, DR. BILL RILEY NEEDS NO INTRODUCTION BUT I WILL PROVIDE BRIEF REMARKS ON HIM BEING THE ASSOCIATE DIRECTOR FOR BEHAVIORAL AND SOCIAL SCIENCES RESEARCH AND DIRECTOR OF OBSR, HIS WORK IS INSTRUMENTAL IN TERMS OF BEHAVIORAL AND SOCIAL SCIENCES PARTICULARLY MANY THE AREA OF DIGITAL TECHNOLOGY TO BEHAVIORAL ASSESSMENT AND INTERVENTION. >> THANKS, WILL. I KNOW WE ARE GETTING TIGHT ON TIME, THERE'S A STORY ABOUT A SHOVER THAT DRIVES PROFESSOR FROM UNIVERSITY TO UNIVERSITY AS HE PRESENTS HIS RESEARCH. AFTER THREE OR FOUR OF THOSE PRESENTATIONS THE SHOVER BETS THE PROFESSOR THAT HE'S HEARD THIS SO MANY TIMES HE COULD PROBABLY GIVE THE PRESENTATION HIMSELF. THE PROFESSOR SHOWS THIS NEXT UNIVERSITY I'M GOING TO NONE OF THEM KNOW ME BY PERSON, IN PERSON SO SURE. GO AHEAD AND KNOCK YOURSELF OUT. SO HE PRESENTS, REASONABLY WELL. AND AS THE PROFESSOR IN THE BACK, SOMEBODY ASKED A QUESTION FAIRLY COMPLICATED ABOUT A CONFUSING SECTION OF THE PRESENTATION THAT HE DID. HE SAID THAT -- THE ANSWER THAT QUESTION IS SO OBVIOUS I'M GOING TO HAVE MY CHAUFFER IN THE BACK ANSWER FOR YOU. I'M IN THAT ROLE. I'M ARTHUR STONE'S CHAUFFER. I WANTED AUTHOR COULDN'T BE HEREINED TO HIT THE HIGH POINTS IMPORTANT IN HIS PRESENTATION AND TRY TO DO THAT QUICKLY. ONE OF THE THINGS THAT I KNOW ARTHUR WANTED TO SAY HERE WAS THAT EMA IS ONE BUT CERTAINLY NOT THE ONLY WAY TO MEASURE A LOT OF THESE PHENOMENA BUT IT HAS A NUMBER OF ASPECTS TO IT THAT ARE IMPORTANT TO SURPRISING VARIABILITY THAT'S IN PAIN, ASSOCIATIONS WITHIN MORE COMPLEX APPLICATIONS, A FEW OF THE THINGS THAT I WILL TOUCH ON REAL QUICKLY FOR HIM. AS I SAID, NOT THE ONLY WAY TO MEASURE IT. BUT AUGMENTS MORE STANDARD MEASURES THAT RELY ON RECALL, HELP US UNDERSTAND THE PROIS ET CETERAS INVOLVED IN STANDARD PAIN ASSESSMENT, ET CETERA, ET CETERA. SO ONE OF THE MANY TOOLS WE HAVE AVAILABLE TO IS IT'S DEFINITELY DIFFERENT THAN AGGREGATING -- AGGRAVATED SELF-REPORTS. SO THE REASON FOR THIS IS NOT SO BECK AGGREGATE, I KNOW MY EARLY STUDIES WHEN I DID THE WORK I WOULD TAKE IT BECAUSE I WAS USED TO AGGREGATE PRE-MID POST HAS BEEN FOLLOW-UP, AGGREGATE DATA THAT SHOULDN'T HAVE BEEN. IT SHOULD HAVE STRETCHED OUT TO UNDERSTAND WITHIN SUBJECT VARIABILITY. SO SOME OF THE KEY THINGS HERE ARE PROCEDURES TO AVOID BIAS DUE TO RECALL, LIMIT THE RECALL PERIOD, RECONSTRUCTION OF THE RECALL PERIOD BASICALLY HELPING PEOPLE THINK THROUGH WHAT HAPPENED IN THE PAST WEEK AND ANCHOR TO VARIOUS ASPECTS AN MORE PRECISE QUESTIONS ABOUT IT. AND LIMIT OUR QUERIES TO INFORMATION THAT CAN BE RECALLED. SOME THINGS ARE NOT THAT EASILY RECALL AND WE HAVE TO BE THOUGHTFUL WHAT SORTS OF THINGS WE DO THERE. I WON'T SPEND TIME HERE, JUST A LOT OF DIFFERENT DIRECTIONS WHICH ECOLOGICAL MOMENTARY ASSESSMENT HAS COME FROM, A LOT OF STREAMS IMPORTANT TO THAT. FEW THINGS ARE IMPORTANT TO ADDRESS HERE. TODAY COLLECTED IN REAL WORLD ENVIRONMENT, SUBJECTS GO ABOUT THEIR LIVES, ECOLOGICAL ASPECT OF IT. THEY FOCUS ON SUBJECTS CURRENT STATE, THE MOMENTARY ASPECT OF IT. AND MOMENT VEG FOR ASSESSMENT, SOMETIMES RANDOM AND SOMETIMES EVENT BASED. THEY CREATE MULTIPLE ASSESSMENTS OVER TIME TO HAVE A MORE CLEAR PICTURE ABOUT BEHAVIORS THEY HAVE HAD. RIGHT NOWADAYS EVERYBODY THINKS ABOUT THIS AS SMART PHONES BUT KEEP IN MIND EARLIER DAYS THESE WERE DONE BY PAGERS AND SELF-REPORT MEASURES AND PENCIL AND PAPER DIARIES, THOSE SORTS OF THINGS, WE ARE NOWADAYS DONE VIA SMART PHONES. AGAIN, RANDOM STRATIFIED RANDOM OR EVENT BASED APPLICATIONS FOR THAT. A FEW OF THE BENEFITS CHARACTER RIDING PERIOD OF TIME FOR ALLOWING ASSESSMENT OF ASSOCIATION BETWEEN TWO OR MORE VARIABLES, THESE TEMPORAL ASSOCIATIONS TIIERNAL CYCLE IS PARTICULARLY IMPORTANT. IT'S OBVIOUSLY A WELL USED APPROACH WITH OVER 17,500 CITATIONS SINCE 2005. THIS IS THE PART I WANTED TO JUST SHOW PEOPLE BRIEFLY BEFORE WE GET INTO OUR DISCUSSION. THIS IS AN EXAMPLE OF ONE PATIENT IN THE MOMENT AND DAYS AND STUDY, TRIANGLES ARE THERE, AVERAGE PAIN RATING FOR THAT DAY. THE AVERAGE ACROSS THESE VARIOUS TIME POINTS, THE DOTS IS A VARIABILITY. SO YOU CAN SEE THE VARIABILITY WITHIN EACH DAY AND ACROSS DAYS IN A SINGLE PATIENT. AS THEY ARE MEASURING TIME IF WE ASK ANY POINT IN TIME TO RETROSPECTIVELY LOOK BACK AND TELL US WHAT PAIN OR AVERAGE AMOUNT OF PAIN TO EXPERIENCE THERE'S A LOT OF HEURISTICS THAT TWO INTHAT IN TERMS OF THINKING PEAK LEVELS MOST RECENT LEVELS THAT BIAS OUR OVERALL REROW SPECKTIVE EXPERIENCE BUT IN REAL TIME YOU CAN SEE THE VARIABILITY THAT HAPPENS. THAT VARIABILITY IS ACROSS PATIENTS IN DIFFERENCES ACROSS PATIENTS IN THAT VARIABILITY AS WELL. THIS IS APPROXIMATE EXAMPLE OF DIFFERENT PARTICIPANTS, AND THEIR PAIN INTENSITY INVESTIGATINGS. YOU CAN SEE THE VARIABILITY WITHIN EACH PARTICIPANT BUT A GREAT DEAL OF VARIABILITY ACROSS. DIFFERENCES IN THE VARIABILITY OF THEIR PAIN RATINGS BY PATIENT. SO WITHIN DAY ASSOCIATIONS, THIS IS RUMTOLOGY AND FM PATIENTS AND TREATMENT, ASSOCIATIONS WITHIN A DAY ON PAIN INTENSITY AND MOOD, SO GOOD RELATIONSHIPS THERE. ASSOCIATIONS OF PAIN INTENSITY AND EMOTIONAL RESPONSES TO PAIN. GOOD RELATIONSHIPS THERE OVER THE COURSE OF TIME, THIS IS INTENSITY OF PAIN. RELATED TO THE ASSOCIATION WITH THOSE EMOTIONAL RESPONSES. THEN WITHIN DAY ASSOCIATIONS EVEN WITH SENSORY QUALITY OF PAIN, WHICH MIGHT BE A LITTLE SURPRISING THINKING DIRECTIONS FOR THIS WORK. EVEN LIMITATIONS THAT ARE DUE TO PAIN, EVEN WITHIN PERSON IN A GIVEN DAY THERE'S VARIABILITY IN THAT AS WELL. LIMITATION TO THE PAIN. RELATIONSHIP WEAN THAT AND THEIR PAIN INTENSITY. LET ME MOVE ON. MUCH GRATER COMPLEXITY DYNAMICS ASSOCIATION WITH TIME AND TIME VARYING -- VARIABLES ARE POSSIBLE. LET ME TOUCH A COUPLE OF THINGS HERE. THAT IS A COMMON STRATEGY, SHAH WHAT WE WANT? WE ARE NOT SURE. DOES IT MAKE A DIFFERENCE TO PATIENTS IN TERMS OF WHAT WE TO, DOES IT PROVIDE WITH OPTIMAL INFORMATION ABOUT THE TREATMENT EFFECT. ALTERNATIVE TO THE AVERAGE REALLY BEEN EXAMINE SOD THIS IS A LITTLE WORK THAT AWE ARTHUR HAS DONE LOOKING AT THAT. IF YOU THINK ABOUT THIS, THEY LOOKED AT A FEW VARIABLES TO LOOK AT OVER COURSE OF TIME, MAXIMUM PAIN LEVELS, AVERAGE PAIN AFTER WAKEUP, PAIN LEVELS PAIN VARIABILITY, A NUMBER OF VARIABLES ACROSS PERIOD OF TIME OVER A NUMBER OF HOURS AND DAYS. HAD DEFINITIONS THEY MADE FOR EACH OF THOSE LOOKING AT THAT. I'LL SKIP QUICKLY BECAUSE I WANT GET TO DISCUSSION. OVERVIEW OF STUDIES BY NIAMS, MAJOR OBJECTIVE WITH DEVELOP NEW INDICES TO REFLECT PAIN AN INTENSITY OVER THE COURSE OF A WEEK, MOMENTARY REPORTS OF PAIN AND INTENSITY REFLECT ASPECTS EXPERIENCED MISSED BY CORP APPROACHES AND WHAT WOULD PATIENTS CLINICIANS AND OTHERS THINK ABOUT THEM AND COLLECT DATA ON THE PSYCHOMETRICS AS WELL. STUDIES IN SERIOUS OF PAPERS, THEY ASK ABOUT INNATE SEIZE OF STAKEHOLDERS, -- INDICES OF SAKE HOLDERS AND CONSTRUCT VALIDITY AND ANOTHER AT CLINICAL TRIAL PERFORMANCE. THIS WAS WORK THAT WAS DONE WITH 20 MINUTE INTERVIEWS BY TELEPHONE, WITH A NUMBER OF PEOPLE WITH PATIENTS MOST HOPING TO ACHIEVE FROM TREATMENT WITH OTHERS, IMPORTANCE OF EVALUATING THE TREATMENT OUTCOME AND THE RANKING WAS FROM MOST IMPORTANT TO LEAST IMPORTANT. LET ME SHOW YOU A COUPLE OF THESE AS WE MOVE FORWARD. I'LL JUMP THROUGH THIS MORE QUICKLY SO WE CAN GET TO THAT. SO IF YOU LOOK AT WHAT PATIENTS TEND TO FOCUS ON THE MOST, CONSIDERED THE MOST IMPORTANT, IT'S WORSE PAIN AND TIME TO HIDE PAIN. TIME IN HIGH PAIN. HOSE TWO THINGS SEEM TO BE MOST SIGNIFICANT FOR THEM AS YOU LOOK AT IT. THAT'S DIFFERENT THAN CLINICIANS FOCUS ON WORST PAIN BEING THE MOST INDICATOR FOR THEM OTHERS BEING LESS. IF YOU LOOK AT CLINICAL TRIALS AVERAGE PAIN IS ONE THEY TENDED TO FOCUS ON THE MOST. ONCE AGAIN WE HAVE THIS PERCEPTIONS OF WORST PAIN AND AVERAGE PAIN, EACH SUBGROUP CONSIDERS THOSE DIFFERENTLY IMPORTANT AS THEY MOVE FORWARD. THE CONVERGENT VALIDITY WORK ALMOST ALL ARE RELATED TO IN THIS CASE PHYSICAL FUNCTIONING WITH THE EXCEPTION OF PAIN VARIABILITY IN THIS CASE TO FATIGUE, AGAIN FOR ALL THOSE VARY USE INDICATORS WITH EXCEPTION TO PAIN VARIABILITY. WITH SOCIAL FUNCTIONING. BE THE EXCEPTION OF PAIN VARIABILITY. WE WERE TALKING ABOUT I SAID WELL BUT PAIN VARIABILITY MIGHT BE USE PHENOTYPIC, CONVERGENT VALIDITY WITH SOME OF THESE OTHER FUNCTIONS NOT SO MUCH. THEIR WORK HAS BEEN LOOKING AT SOME MORE DYNAMIC STRUCTURAL EQUATION MODELING APPROACHES TO BE ABLE TO UNDERSTAND WITHIN SESSION VARIABILITY A LITTLE BETTER WITHIN SUBJECT VARIABILITY BETTER AND LOOK FOR INDIVIDUAL DIFFERENCES IN THOSE METRICS AS THEY MOVE FORWARD. THIS RAISES THE QUESTION ABOUT RA AT THISSAL ASSESSMENTS CLOSER TO THE PAIN EXPERIENCE IN EVERY DAY LIFE, AND HELP POSSIBILITY FORS EXPLORING A HOST OF NEW ASSOCIATIONINGS IN ADVANCE TO ADVANCE KNOWLEDGE. I WILL STOP THERE. AND -- BECAUSE I KNOW WE NEED TO GET TO DISCUSSION. THANK YOU. [APPLAUSE] >> THANK YOU, BILL. LOOKS LIKE WE HAVE ABOUT FIVE MINUTES FOR QUESTIONS. GIVE OR TAKE, FIVE OR SIX MINUTES. STANDARD DEVIATION OF ONE OR TWO. SO WE CAN OPEN THE FLOOR FOR QUESTIONS BEFORE WE MOVE IN TO SESSION NINE. ANY QUESTIONS ON TOPICS HERE? I'LL GO. ALL OF THOSE PRESENTATIONS WERE INCREDIBLY HELPFUL, REALLY APPRECIATE THOSE. THE IMPERSONATOR OF ARTHUR. WE'LL OPEN THIS, WE TALKED ABOUT THIS AT LUNCH WHEN WE WERE SAYING AVERAGING PAIN ISN'T REALLY AS CLOSE TO WHAT PATIENTS AND PEOPLE WITH PAIN DESCRIBE. AND WHAT MATTERS TO THEM. ONCED WE TALKED ABOUT IS UNITED STATING MODE INSTEAD OF AVERAGE WHICH IS SOME OF THE WORK I HAVE DONE EARLY ON WITH HOW FREQUENTLY ARE YOU AD LEVEL 8, HOW FREQUENTLY ARE YOU AT LEVEL 3, THAT'S HAPPENING AT LEVEL 8 AND THAT IS NOT THE KIND OF THING YOU CAN DO FROM MEMORY FROM RECALL BECAUSE IT IS IMPOSSIBLE TO FIGURE THAT OUT. USING EMA IS CRITICAL IN THAT KIND OF MEASUREMENT THING. OTHERWISE YOU JUST LOSE ALL THAT INFORMATION. I SAW ARTHUR TALKING ABOUT TIME SPENT WHICH GETS CLOSER TO THAT. BUT AS WE TALKED EARLIER IN THE DAY, I TEND TO WONDER WE TALK ABOUT WHEN YOU ARE THE WORST BUT WE DON'T TALK A LOT ABOUT WHEN YOU ARE THE BEST. WHAT IT IS THAT'S CHARACTERISTICS OF THOSE TIMES YOUR THOUGHT. >> I WILL CHANNEL AIR HOUR. WHAT HE WOULD SAY AND I HEARD THIS IN OTHER SITUATIONS. WHERE IS CHAUFFER RIGHT NOW. WHAT I THINK HE WOULD SAY IS THAT IS AN EMPIRICAL QUESTION. ONE OF THE THINGS WE NEED TO LOOK AT IS WE CAN PULL ALL KINDS OF INDICATORS OUT OF EMA DATA. WHICH ARE HOSE INDICATORS ARE IMPORTANT FOR PATIENTS WITH MEASURES OF OTHER PHENOMENA, GIVES THE BEST PICTURE FOR A PARTICULAR INDICATION FOR WHAT PURPOSE IS THE OTHER THING WE TALKED ABOUT HERE, FOR WHAT MIGHT BE DIFFERENT INDICATORS FOR DIFFERENT PURPOSER PURPOSES, THAT ACE THE IT DEPEND ANSWER THAT EVERY PSYCHOLOGIST IN THE WORLD GIVES FOR EVERY QUESTION BUT IT'S APPROPRIATE HERE. >> A QUESTION FOR DR. PAPADOPOULOS. YOU MENTIONED ON ONE OF YOUR SLIDES, IT WAS -- THEY WEREN'T HIGHLIGHTED IN RED BUT PART OF THE LIST,SH THE FDA INTEREST IN NOVEL CLINICAL DESIGNS AND ALSO IN REAL WORLD DATA. I WONDERED IF YOU WOULD BE WILLING TO ELABORATE ON THAT. >> SO THESE ARE BOTH AREAS OF GREAT INTEREST UNDER THE LEGISLATION AND THERE ARE A VARIETY OF EFFORTS GOING ON, LET'S TAKE FIRST THE REAL WORLD EVIDENCE THERE WAS A PRAM WORK PUBLISHED AND ON GOING THERE WILL BE GUIDANCE IN THAT ARENA AS WELL SO IT HAS AS LOT OF INTEREST IN TERMS OF THE APPLICATION OF REAL WORLD EVIDENCE I THINK YOU HAVE TO CONSIDER WHAT ARE YOU USING THE EVIDENCE FOR, WHAT IS THE QUALITY OF THE DATA THAT YOU ARE ABLE TO DERIVE FROM THE REAL WORLD EVIDENCE. SO ALL THESE FACTORS WILL NEED TO FEED INTO THAT. I'M ENCOURAGED PERSONALLY BY THE CORE OUTCOME SET ARENA, WE HAVE I HI NEED TO HAVE A CONTINUUM OF CMMON SCALES USED IN CLINICAL PRACTICE AND IN CLINICAL TRIALS IF POSSIBLE. SOMETIMES IT DOESN'T MAKE SENSE. BUT WHERE WE CAN IT'S ALWAYS GOOD TO HARMONIZE THOSE SCALES SO WE CAN UNDERSTAND ONCE A PRODUCT IS LICENSED WE HAVE SOME COMMON METRIC WHICH TO ASSESS PATIENTS. I DO KNOW THAT. YOU KNOW THE PROMISE MEASURES ARE MEASURES THAT ARE ALREADY EPIC AND EHR. BEARE LOOKING AT A LOT OF THOSE IN OUR CLINICAL TRIALS. >> CAN I FOLLOW-UP MAYBE I'LL BE MORE SPECIFIC, SO WITH A PHASE 3 APPROVAL WITH THE FDA CONSIDER PRAGMATIC CLINICAL TRIAL AND WOULD THE FDA CONSIDER A REAL WORLD DATA THAT WAS NOT BLINDED. >> THAT'S SOMETHING I THINK THAT'S THE DEVIL IS IN THE DETAILS. SO I'M GOING TO HEDGE ON THAT BUT -- >> I EXPECTED YOU TO HEDGE ON THAT. THE PRAGMATIC CLINICAL TRIALS ARE YOU CAN THINK OF THEM AS WHAT LARGE RAN TESTIMONYIZE TRIALS, SO WE WOULD GIVE A CONTROL GROUP WHICH YOU CAN ASSESS. THE BOTTOM LINE FOR ANY FOR EVIDENCE IN TERMS OF OUR REGULATION IS THAT WE NEED TO HAVE ADEQUATE WELL CONTROLLED. WHAT THAT HAVE CONTROL LOOKS LIKE THE DEVIL IS IN THE DETAIL BUT WE WANT IT TO BE WELL CONTROLLED, WE WANT A COMPARISON, WHETHER HISTORIC, EXTERNAL CONTROLS OR RANDOMIZE STUDY OR WHAT HAVE YOU. >> WE LIKE PRAGMATIC TRIALS AND THERE'S NEW LEARNING HEALTHCARE SYSTEMS THAT ARE BEING EMPLOYED THAT ARE HELPING HEALTHCARE SYSTEMS AND HOW THEY PROCESS RESEARCH WISE ALLOWING HOME UM BUT THAT IS THE PROBLEM WITH PRAGMATIC TRIALS PEOPLE ARE ASSIGNED TO GROUPS, NOT RAN TOM. IT'S BASED ON CLINICAL JUDGMENT, THINGS LIKE THAT. SO THAT'S -- YOU DON'T REALLY -- YOU ARE NOT REALLY DOING AN EXPERIMENT. >> THAT'S WHY THE DEVIL IS IN THE DETAILS. >> I WAS INTRIGUED BY YOUR REMARKS, SPECIFICALLY THE OPIOID SPARING ASPECT. COULD YOU EXPOUND HOW Y'ALL OPERATIONALLIZE OPIOID SPARING AND HOW TOW DO THAT IN YOUR CLINICAL END POINTS. >> I DON'T HAVE HANDS ON EXPERIENCE. T WE HAVE WORKED TO (INAUDIBLE) MEASURING THE USE OF OPIOIDS KNOWLEDGE (INAUDIBLE) DEFINITELY SOMETHING WE ALL WANT TO ACCOMPLISH. WANT DEVELOP. OPERATIONALLIZING (INAUDIBLE) THINKING ABOUT (INAUDIBLE) >> I'M INVOLVED IN SEVERAL STUDIES FUN LEWD THE VA OR PCORI LOCKING AT ALTERNATE PAIN STRATEGIES TO REDUCE OPIOIDS. THE PROBLEM THAT WE HAVE RUN INTO IS THAT IT'S NO LONGER POLITICALLY IN THE UNITED STATES, A SITUATION WHERE PEOPLE ARE CHOOSING OR HAVE THE CHOICE TO REDUCE THEIR OPIOIDS BUT THEY EITHER HAVE BEEN COMPLETELY TAPERED OFF DISCONTINUED OR FORCED REDUCTION, THAT LEADS THE QUESTION WHAT'S DIFFERENT ABOUT PEOPLE, WHAT MAY BE DIFFERENT BETWEEN TWO GROUPS OF PEOPLE BETWEEN THOSE WHO WANT TO REDUCE VERSUS THOSE WHO ARE JUST FORCED REDUCTION. SO IT'S A COMPLICATED QUESTION. >> UNFORTUNATELY WE HAVE TO MOVE ON. THIS WAS A VERY GREAT DISCUSSION. I'M GOING TO HAND IT OVER TO DR. TURK. >> THANK YOU. THIS IS REALLY BEEN A LOT OF FUN TO TRY TO LISTEN TO DISPARATE PRESENTATIONS BUT ALL FOCUSED ON THE SAME THING, WHICH IS PAIN AND ASSESSMENT AND ANSWERING THE QUESTION OF WHAT ARE THE BIOLOGICAL APPROACHES OUTCOMES, MEASURES, WHAT ARE THE PSYCHOLOGICAL APPROACHES OUTCOMES MEASURES AND WHAT SOCIAL FACTORS NEED TO BE CONSIDERED TOPIC FOR THIS CLOSING SESSION WHICH IS SOMEWHAT OF A SUMMARY PULLING TOGETHER THINGS, TOWARD THE COMPLEX COMPOSITE MEASURE AND WHERE EACH OF THE PANEL ITSELFS, IS DR. BORSUK STILL ON? NO? >> SO WHAT THE THREE OF US ARE GOING TO DO IS TO TRY TO GIVE A LITTLE BIT OF A PERSPECTIVE MAYBE ON SOME DIRECTIONS AND WOULD REALLY LIKE US -- I WILL FOCUS. WHAT GUIDANCE CAN WE TAKE AWAY FROM THIS TO GIVE TO FDA TO NIH THEY SHOULD BE THINKING ABOUT IN FUNDING BUT ALSO HIKING OUTCOMES AND WHAT THEY IMMEDIATE FOR OUTCOMES. THAT IS REALLY WHERE THE END PRODUCT SHOULD REALLY BE, DO WE HAVE AN IMPACT ON THOSE WHO HAVE DECISION MAKING, I'M ASSUMING WE HAVE IMPACT ON EACH OTHER AND HOW WE MIGHT THINK ABOUT THINGS. THAT'S GOOD. WHAT WOULD BE GREAT IS IF WE CAN GET OUR COLLEAGUE SO I'LL START OFF WITH JUST A COUPLE OF -- WE WERE TOLD TO TAKE A FIVE MINUTES MAX TO TALK AND HA MEANS FOR ME, TEN. BUT I WILL DO MY BEST, COUPLE OF POINTS I WANT TO REITERATE. ONE OF THE KEY THINGS THAT WE HOPEFULLY HEARD OR SHOULD HAVE HEARD WAS THAT THE TOWARD THIS COMPREHENSIVE MEASURE DEPENDS ON THE QUESTION WE WANT TO ANSWER. IF WE ARE DOING A RESEARCH STUDY WHERE WE CAN BE INTENSIVE AND SPEND TIME AND INVEST EMERGENCY WE CAN USE MORE COMPLEX MEASURES FOR STRATEGIES FOR GATHERING THAT INFORMATION. IF WE ARE TRYING TO TO SOME EPIDEMIOLOGY RESEARCH, ABOUT PREVALENCE AND THE FACT WE DON'T HAVE THE OPPORTUNITY TO USE SOME OF THESE DIFFERENT TECHNOLOGIES, SO AN IMPORTANT HINGE TO KEEP IN MIND IS WHAT IS COMPREHENSIVE APPROACH, LET'S GO FROM THE CLINICAL EPIDEMIOLOGY SIDE, THE CLINICAL PRAXIS SIDE, WHAT PRACTICAL USE BE MENTIONED, I JUST HEAD YOU DIDN'T EVEN KNOW THAT PROMISES ELECTRONIC MEDICAL RECORD SO THAT IS ADVANCED. OF ALL OTHER KINDS OF THINGS WE ARE HEARING ABOUT FROM WHERABLE TECHNOLOGY TO IMAGING PROCEDURES, TO QST, WHAT IS REALISTIC GIVEN IF A QUESTION WE WANT TO LEARN SOMETHING ABOUT THE PREVALENCE OF DIFFERENT TYPES OF PAIN CONDITIONS WHEN WE TALK ABOUT PREVALENCE OF PAIN CONDITIONS, THAT'S -- ANOTHER HEME FOR ME IS THE COMPLEXITY OF ANSWERING THAT QUESTION PARTIALLY DEPENDS ON THE NATURE OF THE PAIN CONDITION YOU TALK ABOUT ACROSS ALL PAIN CONDITIONS. FOR EXAMPLE MIGRAINE WHICH IS EPISODIC QUITE DIFFERENT THAN CHRONIC LOW BACK PAIN, IF WE HAD SOMEONE TALKING SICKLE CELL DISEASE THAT'S QUITE DIFFERENT FROM WHAT WE THINK ABOUT OR NEUROPATHIC PAINFUL DIABETIC MURR ROUP THINK SO THAT ALSO IS SOMETHING WE HAVE TO KEEP IN MIND, WHAT POINT CAN YOU DEVELOP A GENERIC COMPREHENSIVE MEASURE MENT FOR DIFFERENT POPULATIONS FOR DIFFERENT PURPOSES AND MAYBE THAT'S NOT REALLY THE RIGHT, IT'S WRONG. YOU CAN'T DO IT. WHAT WE CAN SAY IS NOR EACH DIFFERENT USE, ARE THERE BIOLOGICAL PSYCHOLOGICAL AND SOCIAL FACTORS THAT SHOULD BE CONSIDERED. THIS IS WHY I ENCOURAGE NIH MANY THE BACK PAIN AREA FOR EXAMPLE, THEY HAD A TASK FORCE ON CORED ELEMENTS, CORED DATA SETS FOR VA HAD A SIMILAR MEETING WHICH I -- FRANK I DON'T KNOW IF YOU WERE ONE OR MORE OF THOSE BUT WE CAME UP WITH SOME RECOMMENDATIONS FOR EPIDEMIOLOGICAL STUDIES, AS WELL AS WHAT COULD BE IN MORE CLINICALLY ORIENTED STUDIES. THE PURPOSE OF THAT WAS TO SAY CAN WEING A AGGREGATE INFORMATION ACROSS MULTIPLE SETTINGS AND THINGS, FOR FUN, TAKE A MINUTE OF MY TIME, THINK ABOUT PRESENTATION OF SLIDES AT THIS MEETING AND ANY MEETING AND THE USE OF CITATIONS. SOMETIMES WE HAVE PEOPLE WHO SAY WE DID A STUDY OR JOE BLOW DID A STUDY ON AND THERE'S NO CITATION. SOMETIMES THERE'S A CITATION TO JOE SMITH, CITATION JOE SMITH IN 1979. SOMETIMES CITATION JOE SMITH 1979 PUBLISHED IN PAIN IN 37 PAGE 132 TO 147. THERE IS CONSENSUS OR CONSISTENCY AMONG US, EVEN SOMETHING ABOUT WHAT IS THE BEST WAY TO CONVEY INFORMATION, THINK ABOUT THAT WHEN IT COMES TO ASSESSMENT, EVERYBODY HERE HAS A DIFFERENT WAY USING DIFFERENT MEASURES. AND THERE MAY OR MAY NOT BE AGREEMENT AMONG THOSE SO I WOULD ENCOURAGE NIH AND OTHER AGENCIES TO BE THINKING ABOUT CAN YOU LOOK AT SOME GROUPING, SOME MEETINGS, SOME CONSENSUS CONSENSUS STATEMENTS ABOUT WHAT ARE THE BEST WAYS TO MEASURE WHAT CONSTRUCT YOU THINK IS IMPORTANT. IF YOUR CONSTRUCT DOES MORE PAIN INTENSITY AND YOU WANT CONSTRUCT EMOTIONAL FUNCTION AND PHYSICAL FUNCTIONING, IF THOSE ARE THREE CONSTRUCTS ARE THERE SOME COMMON MEASURES THAT ARE GENERIC OR DO THEY HAVE TO BE SPECIFIC. EASY TO THINKN'T A COMMON MEASURE WITH ANXIETY, DEPRESSION, IT'S NOT SO EASY TO THINK OF A COMMON MEASURE FOR PHYSICAL FUNCTION, PHYSICAL FUNCTIONING MAY BE RELATED TO NATURE OF THE PAN CONDITION YOU ARE TALKING ABOUT. WE NEED TO BE THINKING -- SO IT'S QUESTIONS THAT NEED TO BE ADDRESSED. BUT I KEEP EM PA SIZING THIS IDEA OF CONSENSUS BECAUSE I DON'T THINK THE FIELD IS GOING TO ADVANCE VERY FAR IF WE WE STAY IN SILOS AND EACH USE PREFERRED METHODOLOGIES AND TECHNIQUES, DIFFERENT WAYS OF COLLECTING THE DATA ANALYZING THE DATA, PRESENTING. THAT'S ONE THEME. ANOTHER THEME THAT IS GENERAL TO THIS WHOLE FIELD, NOT JUST TO THIS MEETING, IS GOING FROM FROM RESEARCH TO IMPLEMENTATION. I HAVE ENOUGH GRAY HAIR TO HAVE BEEN AROUND FOR LOTS OF DIFFERENT -- HUNDREDS, THOUSANDS OF STUDIES THAT I HAVE SEEN, BEEN INVOLVED WITH, OTHER PEOPLE STUDIES AND WE LOOK AT WHETHER THIS IS PICKED UP AND USED IN CLINICAL PACK PRACTICE. I DON'T KNOW IF WE DO A VERY GOOD JOB. WE DO NOT DO A GOOD JOB OF TAKING THE RESULTS OF OUR STUDIES AND MOVING THEM FORWARD TO THEY HAVE SOME IMPACT ON END USER AND THE END USER COULD BE THE FDA, END USER COULD BE PATIENT CLINICAL PRACTITIONER, BENEED TO FIND WAYS TO GET THAT INFORMATION. THE FDA NICELY DR. PAPADOPOULOS SPELLED OUT GUIDANCE WHAT PROCEDURES ARE TO GET THE END POINTS TO BE CREDITED. WE NEED A COMMON THING TO BE TRUE SIMILAR TO THAT FOR OTHER MEASURES. IF IN FACT WE CAN COME UP WITH SOME WAY OF USING THAT INFORMATION FINDING A WAY TO GET INFORMATION DISSEMINATED AND ONE STEP FURTHER, BEING PAID FOR BY SOMEONE BECAUSE IF IN FACT WE SUGGESTED, NOT SUGGESTING WE DID BUT EVERYBODY IN A CHRONIC PAIN STUDY SHOULD HAVE FMRI. THAT'S EXPENSIVE, I DON'T THINK WE'RE GOING TO FIND TOO MANY WHO WILL DO FROM EXPERIMENTAL TREATMENT THEY'RE GOING TO PAY FOR ME TO HAVE THIS. SO I THINK WE NEED TO BE CAUTIOUS, FROM THE INDUSTRY STANDPOINT, WE ALSO HEARD THAT CERTAIN KINDS OF PROCEDURES ARE TOO EXPENSIVE FOR THE PHARMACEUTICAL INDUSTRY TO USE SO WE HAVE TO SAY ANOTHER QUESTION IS ARE WE DEVELOPING A CORE OUTCOME SET, A CORE SET OF MEASURES, A CORE WAY OF GOING ABOUT THIS, THAT'S RELEVANT FOR THAT PARTICULAR GROUP WHICH MAY BE NOT ADS RELEVANT FOR SOMEONE DOING A LABORATORY PAIN STUDY NIH FUNDED KINDS OF STUDY. SO THERE'S A CONSENSUS ISSUE, AND THERE'S DISSEMINATION. THOSE ARE TO ME TWO OF THE BIG THINGS FROM ALL THE PRESENTATIONS I HEARD. ONE WORRY ABOUT CONSENSUS, I WILL STOP, MY FIVE MINUTES IS LONG GONE. FOR SOME OF THE TECHNOLOGIES THAT WE ARE HEARING ABOUT, THE ADVANCES ARE HAPPENING SO QUICKLY, IF WE CAN'T GET CONSENSUS ABOUT THE BEST DEVICE FOR AXELROMETRY, SIX WEEKS LATER WE WOULD BE OUT OF DATA WITH POTENTIAL EQUIPMENT THAT'S AVAILABLE. ARE THERE COMMON IDEAS THAT WOULD BE RELEVANT REGARDLESS OF WHETHER THE TECHNOLOGY ADVANCES CERTAIN WAYS OF GATHERING THE NEW DATA, CERTAIN WAYS OF PRESENTING NEW DATA AND ANALYZING THE DATA REGARDLESS OF DIFFERENT METHODS USED TO COLLECT THE DATA. THAT'S A CAVEAT TITLE THIS WHOLE MEETING WAS ON CAVEAT. CAVEAT FOR WHEN YOU DO THINK ABOUT CONSENSUS, THOUGH I'M STRONGLY PUSHING IT SO LET ME STOP MORE THAN ENOUGH FOR ME. AND LET ME SEE -- ASK DR. KEE, FRANK, YOU HAVE BEEN SITTING THROUGH THIS AND YOU HAVE ONE OR TWO GRAY HAIRS. YOU HAVE BEEN AROUND FOR WHILE. SO YOUR THOUGHTS. BUT I WOULD LIKE YOU TO NOT ONLY JUST THINK ABOUT THIS MEETING BUT WHAT YOU LEARNED FROM THIS MEETING AND OVER YOUR MULTIPLE YEARS WHAT WE CAN FORM THE FDA AND NIH ABOUT ISSUES OF ASSESSMENT AND WHAT THEY SHOULD BE THINKING ABOUT. >> THANK YOU, DENNIS. YOU TALKED ABOUT YOUR BRAY HAIR. I WON'T SAY ANYTHING ABOUT BRAY HAIR. I WILL SAY I'M VERY GLAD TO HAVE HAIR. TO THIS POINT IN MY LIFE. I'M VERY GLAD. HOPEFULLY WILL STIMULATE SOME DISCUSSION. THE FIRST IS, I'M CHANNELING BILL FORDEIS WHO INFLUENCED SO MANY OF US, WE ARE MISSING A MAJOR OPPORTUNITY IN ADDITION FIELD. WHEN I LOOK AT THE AHRQ OF PAIN MEASUREMENT, THINKING ABOUT PAIN OVER THE COURSE OF MY CAREER, WHAT WE ARE MISSING IS THE OPPORTUNITY REALLY TO UNDERSTAND HOW REPORTS OF PAIN WE GATHER FROM OUR PATIENTS VARY AS A FUNCTION OF THE SOCIAL CONTEXT WHICH THOSE ARE GATHERED. THIS MEETING HAS SOCIAL IN THE TITLE L. ORBITED L. BIOPSYCHOSOCIAL MODEL IS TOUTED. WHAT I OFTEN FIND IN THE LITERATURE, AND WHAT PEOPLE ARE DOING IN RESEARCH IS THEY MENTION BIOPSYCHOSOCIAL, THEY ARE ALL IMPORTANT AND SOMEBODY WILL TALK ABOUT MOSTLY THE BIOLOGICAL MECHANISM. SOMEBODY ELSE WILL TALK MAINLY ABOUT THE PSYCHOLOGICAL MECHANISM. BUT THE SOCIAL MECHANISMS AND CONTEXT, ARE SO RARELY MENTIONED. IN DEPTH. THEY ARE KIND OF I TOUCH THAT, THAT'S ALL RIGHT. WHATEVER. I THINK ALL OF US KNOW THAT THE PEOPLE THAT SUFFER FROM PERSISTENT PAIN ARE IN A WIDE VARIETY OF SOCIAL SITUATIONS. WE ALSO KNOW THOSE SETTINGS PROVIDE IMPORTANT OPPORTUNITIES FOR INTERACTIONS. WE SEE SOME INTERACTIONS THAT HAVE TRAUMATIC EFFECT IN REDUCING PAIN. SOMETIMES AN EFFECT THAT'S MORE POWERFUL THAN ANY DRUG WE CAN GIVE SOMEBODY. CONVERSELY WE SEE INTERACTIONS IN THOSE SETTINGS THAT DRAMATICALLY INCREASE PAIN. I THINK THAT WITH JUST A FEW EXCEPTIONS WE DIDN'T REALLY GO INTO DEPTH; YOU LOOK HOW PEOPLE IN THIS FIELD ARE OPERATIONALLIZING THE SOCIAL CONTEXT, I TOOK A MEASURE OF LIFE STRESSORS. THIS PERSON HAD SOME TRAUMA OR I TOOK A MEASURE OF SOCIAL SUPPORT OR SOCIAL ISOLATION. TONYA'S TALK I THINK ILLUSTRATED MORE TAKE MEASURES FROM PARENTS, SEE WHAT'S HAPPENING. THE PARENTS VIEWS, SO ON SO FORTH. I THINK WE HAVE MEAGER WAYS OF OPERATIONALLIZING THIS, WE ARE GIVING SHORT SHIFT. YOU MIGHT SAY WHY IS THIS IMPORTANT? IT'S INC ABLY IMPORTANT NOT ONLY DO YOU HAVE AN OPPORTUNITY TO BETTER UNDERSTAND WHAT PERSONS ARE TELLING YOU ABOUT THEIR PAIN, YOU ALSO HAD AN OPPORTUNITY TO DEVELOP NOVEL INTERVENTIONS. THERE'S VERY NICE WORK GOING ON IN THE CANCER PAIN AREA INVOLVING DYADS, CAREGIVERS AND PATIENTS, STRATEGIES FOR REGULATING PAIN WITH MEDICATIONS AND NON-MEDICATIONS. THAT CAPITALIZE ON SOME OF THE ADVANCES THAT ARE OCCURRING IN OUR UNDERSTANDING OF THE SOCIAL CONTEXT OF PAIN AND OTHER SYMPTOMS. SO SO THE FIRST THING I WOULD CHALLENGE ALL OF US HERE TO THINK ABOUT IS, HOW CAN WE MORE MEANINGFULLY INTEGRATE THAT SOCIAL CONTEXT INTO HOW WE UNDERSTAND PAIN. SOME OF YOU MAY KNOW CRAIG AND AMANDA WILLIAMS ARGUE WE CONSIDER PAIN AS A SOCIAL CONSTRUCT. THEY WANTED TO CHANGE THE DEFINITION OF PAIN TO INCLUDE SOCIAL MENTION. THAT'S ONE THEME. HOW CAN WE DO THAT? I THINK THERE'S SOME NEW WAYS WE CAN APPROACH, THIS WAS RESEARCH I THINK IT NEEDS TO BE CLEARLY RECOGNIZED THIS IS AN UNDERSTOOD STUDY BUT EXTREMELY IMPORTANT AREA. THE SECOND, I'M STILL BLOWN AWAY, STILL REACTING TO KRISTEN'S TALK ON THE IMPORTANCE OF INTEGRATING THE PATIENT PERSPECTIVE. I'M SO THANKFUL THAT FDA IS TAKING THIS SERIOUSLY, NOT ONLY IN T PAIN AREA BUT OTHERS. HOW DO WE MEANINGFULLY INTEGRATE? I WANT TO TWO BACK TO THE REPORTS YOU SENT ME AND REALLY THINK ABOUT, IT LAYS OUT A WHOLE RESEARCH AGENDA. HOW DO WE MEANINGFULLY INTEGRATE THAT PERSPECTIVE INTO WHAT WE ARE DOING AS PAIN SCIENTISTS AND PAIN CLINICIANS. ALSO FOR PEOPLE MAKING DECISIONS, POLICY DECISIONS ABOUT PAIN, IT'S EXTREMELY IMPORTANT AND I THINK THERE ARE SOME RICH WAYS TO TO THAT AND VERY NOVEL WAYS SO ANOTHER THING THROW OUT TO THE GROUP. THINK ABOUT YOUR OWN WORK. HOW CAN YOU MEANINGFULLY INTEGRATE THAT PERSPECTIVE HOW YOU'RE UNDERSTANDING. THE THIRD PART SOMETHING BOTHERED ME THROUGHOUT THIS MEETING AND CAREER, THAT IS WE DEVELOP THESE WAYS TO ASSESS PAIN, WE WERE HAPPY WHEN WE GOT THE BPI AND 0 TO 10 SCALE LESS STANDARDIZED. YOU SEE THIS STUFF MIGRATE INTO CLINICAL PRACTICE. IT'S WHAT I TALK ABOUT WITH PAIN AS A FIFTH VITAL SIGN. LOOK WHAT HAPPENED. REMEMBER THE SLIDE I HAD WITH THE 0 TO 10. IT'S A THREE WE'RE GOING TO DO THIS, IF A FOUR -- YOU TAKE SOMETHING THAT WE ALL KNOW IN OUR HEARTS OF HEARTS SOMEBODY GIVES YOU TEN THERE'S A LOT THAT GOES INTO THAT. WHEN YOU ARE ASKED TO GIVE A TEN, SOMETIMES IT'S SILLY YOU OOH SITTING THERE. YOU WANT ME TO TAKE THIS EXPERIENCE AND PUT IT INTO A -- YOU GOT TO BE KIDDING ME, WE DO IT ALL THE TIME. IN OUR RESEARCH. THERE'S TENSION THROUGHOUT PAIN IS COMPLEX BUT WE GOT TO MEASURE IT SIMPLY IN THE CLINICAL SETTING OR DIARY, WHATEVER. AND IT SEEMS TO ME SINCE WE ARE SO DEPENDENT, EVEN THE RESEARCH WE HEARD ABOUT WEARABLES AND COLLECTING DATA OBJECTIVELY, YOU ARE VALIDATING IT AGAINST WHAT SOMEBODY IS SAYING ABOUT THEIR EXPERIENCE. SO WONDERING TO WE NEED SOME NEW RESEARCH APPROACHES TO TEST INTERVENTIONS TO TEACH CONSUMERS, CLINICIANS, TO TEACH RESEARCHERS, POLICY MAKERS, HOW DO YOU ACTUALLY UNDERSTAND AND INTERPRET THE DATA THAT COMES FROM MEASURES THAT ARE CURRENTLY BEING -- WHAT ARE THE THINGS MANY OF US LEARN IN OUR PSYCHOMETRIC CLASSES, I THINK SOME OF US HAVE FOR GOTTEN AS WHICH GO WITH OUR CAREERS, WE TEND TO REAFIE, SOME OF THESE THINGS, WE GOT THIS REPORT OF PAIN IN THIS SITUATION, THAT CHARACTERIZES THIS GROUP OF PATIENTS. THEY ARE PROBABLY GOING TO STAY LIKE THAT. YOU KNOW THEY CAN CHANGE. SO HOW DO WE TEACH PEOPLE TO REALLY APPRECIATE, ALMOST LIKE TEACHING SOMEBODY TO UNDERSTAND THE RESULTS OF ANY TEST, IF YOU ADMINISTER STANDARDIZED TEST WHAT DO YOU NEED TO KNOW? ABOUT THAT TEST? AND HOW IT'S GIVEN. YOU WANT TO BE SURE IT'S DONE IN STANDARD ADVERTISED FASHION. AND WHAT YOU KNOW WHAT THE ITEMS ARE LATHER THAN JUST THIS IS THE AVERAGE. I WAS TALKING TO BILL, I THINK THIS THIS IS NOT ONLY IMPORTANT FOR ESTABLISHED MEASURES BUT WE HAVE THESE NICE NEW MEASURES THAT HAVE A LOT OF REALLY NEAT ASPECTS, COGNITIVE TESTING AND LARGE VALIDATION SAMPLE. WE HAVE NEW WAYS TO USE IT LIKE IN CATTY, COMPUTERIZED ASSISTED TESTING. CLINICIANINGS ARE NOT EDUCATED. AND EVEN PATIENTS ARE NOT EDUCATED ABOUT WHAT CAN THAT DO. OR WITH EMA. HOW DO WE INTERPRET EMA, TEACH PEOPLE TO USE THIS. FROM SO THAT IS A RESEARCHABLE AREA. IT CAN BE DONE, I CAN SAY ANY OF YOU IN A VARIETY OF SETTINGS, CLINICS IN THIS ROOM ARE SOPHISTICATED. IN THE WAY THEY UNDERSTAND THIS. IF YOU GO OUT INTO MANY PRIMARY CARE SETTINGS, AND YOU SEE THE WAY THESE MEASURES ARE USED, AND THE WAY THAT PAIN IS CONCEPTUALIZED, IT WAS 50 YEARS AGO. THIS NEED FOR EDUCATIONAL INTERVENTIONS PROBABLY NOT FOR PEOPLE IN PAIN CLINICS BUT I THINK BROADLY IT IS VERY MUCH NEEDED. PARTICULARLY AT THIS TIME WHEN THERE'S SUCH A CONCERN ABOUT CHRONIC PAIN, OPIOIDS, HOW PAIN SHOULD BEST BE TREATED. SO THOSE ARE THE THREE THINGS I WOULD LIKE TO GET GROUP TO THINK ABOUT FIRST SOCIAL CONTEXT OF PAIN, HOW CAN WE DO A BETTER JOB WITH THAT, SECOND, BEYOND WHAT WE HAVE HEARD, HOW CAN WE MEANINGFULLY INCORPORATE TRULY INCORPORATE THE PATIENT PERSPECTIVE ON WHAT WE DO. THIRD, HOW DO WE AVOID THE TENDENCY TOWARDS OVERSIMPLIFICATION. FROM WE ALL WANT A SIMPLE -- THIS IS A COMPLEX PROGRAM, DAVID DID REALLY GOOD JOB. THIS IS COMPLEX. THE FIGURES WILL BE COMPLEX. HOW DO WE AVOID THAT OVERSIMPLIFICATION, HOW TO WE HELP THOSE WHO CONSUME SIMPLE MEASURES TO UNDERSTAND A LOT GOES INTO THESE AND WHEN YOU ARE INTERPRETING THEM YOU NEED TO BE AWARE OF THAT. SO THREE THINGS TO THINK ABOUT. >> I HAVE TO REFLECT ON HL MENKIN A JOURNALIST IN BALTIMORE A LONG TIME AGO AND HE MADE THE STATEMENT FOR EVERY COMPLEX PROBLEM THERE IS A SIMPLE SOLUTION AND IT'S HUGELY WRONG. OKAY. SO OUR THIRD PANELIST WHO WE HAVE A DISTINCTION HONOR BECAUSE THIS PANELIST WAS NOT HERE FOR THE MAJORITY OF THE MEETING, THEREFORE HE COMES AT IT WITH FRESH EYES. I'M DELIGHTED TO HAVE HIM HAVE THE LAST WORD OF THE PANELISTS BEFORE WE OPEN IT UP. THAT'S DR. WANG FROM NYU UNIVERSITY SCHOOL OF MEDICINE. HE HAS A UNIQUE BACKGROUND IN THAT HE HAS A JD DEGREE AS WELL AS MD DEGREE. WE HAVE -- IT'S WRONG, IT'S NOT UNIQUE, NO LONGER UNIQUE. >> HE IS PROFESSOR DIRECTOR OF INTEGRATED PAIN PROGRAM, VICE CHAIR OF CLINICAL TRANSLATIONAL RESEARCH, DEPARTMENT OF ANESTHESIOLOGY PERIOPERATIVE PAIN PALLIATIVE CARE NYU SCHOOL OF MEDICINE. YOU HAVE THE CHANCE TO REALLY CAPTURE THE AUDIENCE SO WE'RE COUNTING ON YOU TO BRING IT HOPE. >> THREE THINGS I WOULD LIKE TO ADD TO THE OVERALL DISCUSSION. I THINK HE DID A GOOD JOB TALKING TO SOCIAL CONTEXT, AS A CLINICIAN I COULDN'T SAY ENOUGH ABOUT HOW IMPORTANT THAT IS. FROM SOCIAL COMPLEX. I WANT TO PUT THAT INTO A DIFFERENT WAY OF THINKING. THE FIRST POINT I WANT TO BRING UP IS TIME. TIME IS IMPORTANT FOR CLINICAL CARE IN BIOLOGICAL SYSTEMS IN GENERAL. IT'S PARTICULARLY IMPORTANT FOR PAIN BECAUSE WE TALK ABOUT PAIN, ATTRIBUTED TO ONE THING BUT IT'S NOT. SO ACUTE PAIN IS VERY DIFFERENT FROM CHRONIC PAIN. ACUTE PAIN COULD BE TRAUMA INDUCED PAIN THAT LASTS A FEW MINUTES AND THEN TRIGGER A SET OF BEHAVIORAL PSYCH LOCKCAL RESPONSES THAT ARE NOT PRESENT AT ALL IN SOMEONE WITH CHRONIC PAIN. IT IS VERY IMPORTANT AND ALL MEASUREMENTS THE TOOLS WE USE TO MEASURE ACUTE PAIN AND CHRONIC PAIN MAY NOT OVERLAP. THAT'S REALLY IMPORTANT TO THINK ABOUT. MOVING TO THINKING ABOUT MEASUREMENTS THAT WE HAVE, FROM FROM THE TOOLS WE HAVE THERE ARE DYNAMIC MEASUREMENT TOOLS AND THEN THERE ARE MORE STATIC TOOLS. FOR EXAMPLE, SOME QUESTION MEASURE MORPHINE MIC RESPONSE YOU HAVE. COULD BE SOMETHING LIKE A VAST SCORE MOMENT THAT'S DYNAMIC. THAT CAN CHANGE THE VAST WORLD TODAY CAN CHANGE FROM THE VAST WORLD FROM YESTERDAY YOU ALSO HAVE TOOLS THAT ARE STABLE AND MEASURES OVERALL CONDITION, CERTAIN AMOUNT OF TIME, CERTAIN MEASUREMENTS WITHIN BPI FOR EXAMPLE. GIVES YOU AVERAGE RESPONSE OVER SEVERAL DAYS OR AT LEAST A DAY. SO THERE ARE DYNAMIC AND STATIC TOOLS IN TERMS OF QUESTIONERS AND TOOLS IN TERMS OF BIOLOGIC MEASURES. THAT'S SOMETHING VERY IMPORTANT TO THINK ABOUT. IF YOU U DRAW BLOOD, WANT TO MEASURE BLOOD BIOMARKERS THAT'S A MORE STABLE STATIC CONDITION, THAT'S NOT GOING TO CHANGE VERY QUICKLY. YOU ARE NOT GOING TO BE ABLE TO CAPTURE THAT WHATEVER GENOMIC OR GENETIC CHANGE THAT QUICKLY WITHIN A MINUTE. IN CONTRAST IF YOU MEASURE THINGS LIKE EUG YOU ARE ABLE TO GET SOMETHING VERY DYNAMIC. DYNAMIC RESPONSE TO A MOMENT OR WHATEVER SENSORY QUEUE WE HAVE SO IMPORTANT THINK ABOUT DYNAMIC MEASUREMENTS AND STATIC MEASUREMENTS. AND SOME OF THE STATIC MEASUREMENTS ARE VERY IMPORTANT FOR CHRONIC PAIN CONDITION. OR TO LOOK AT SOME OF THE PSYCHOSOCIAL CONDITION THAT PRIMES ACUTE PAIN RESPONSE. IN CONTRAST DYNAMIC RESPONSE COULD AT THE SAME TIME REVEAL REALLY IMPORTANT INFORMATION ABOUT CHRONIC PAIN BECAUSE CHRONIC PAIN IS GOING TO ALER WAY OF RECEIVING ACUTE SENSORY AFFECTIVE EXPERIENCES. BUT IT'S IMPORTANT TO PUT THOSE TOOLS INTO CONTEXT FOR THE QUEUE AND CHRONIC PAIN. THE SECOND POINT I WANT TO BRING UP IS THIS INTERFACE BETWEEN AMONG BEHAVIORAL SOCIAL AND BIOLOGICAL FACTORS. I THINK BOTH TENNIS AND FRANK TALK ABOUT THERE ARE -- WE KIND OF OPERATE IN OUR OWN BUBBLES, WORK BEHAVIORAL SOCIAL OR BIOLOGICAL FACTORS. BUT IN FACT, THERE ARE MANY AREA S OF INTERACTION. FOR EXAMPLE NOW IN OUR LAB WE ARE INTERESTED IN UNDERSTANDING NEURAL BASIS FOR CERTAIN AFFECTIVE EXPERIENCE OF PAIN. OPPOSED TO SENSORY EXPERIENCE OF PAIN. I THINK IF WE LOOK DEEPER WE CAN FIND NEURAL CORRELATES OR SOME BIOLOGICAL CORRELATE OF CERTAINLY BEHAVIORAL CONDITIONS BUT EVEN BIOLOGICAL CORRELATES OR BASIS FOR HOW WE RESPOND TO CERTAIN OR MANY DIFFERENT SOCIAL CONTEXT. SO THERE'S A LOT OF OPPORTUNITY RIGHT NOW TO CORRELATE THESE BIOLOGICAL FINDINGS WITH BEHAVIORAL SOCIAL FINDINGS. SOME OF THE HUMAN RESEARCH IS MOVING IN THAT DIRECTION, THAT HE'S REALLY GREAT. AND ALSO PARTICULAR CHALLENGE OBVIOUSLY FOR ANIMAL RESEARCH. ANIMAL RESEARCH OBVIOUSLY LET A RAT TELL US THE SOCIAL CONTEXT OR BEHAVIORAL CONDITION VERY WELL AT THAT MOMENT. SO THAT IS A CHALLENGE FOR ANIMAL RESEARCH BUT WE HAVE TOOLS NOW. WE HAVE A LOT OF TOOLS FOR HUMAN RESEARCH. AND WE INTEGRATE INTO BEHAVIORAL AND SOCIAL NEUROSCIENCE SO MAYBE INTERESTING TO BRING SOCIAL NEUROSCIENTIST, BEHAVIORALLIST TOGETHER WITH NEUROSURGEON WHO HAS IMPLANTS IN THE BRAIN OF A PATIENT AND CONDUCT THIS EXPERIMENT TO UNDERSTAND NEURAL CORRELATES OF SOCIAL BEHAVIORAL COMPLEX. A THIRD POINT I WANT TO BRING UP IS TOWARDS BUILDING THIS COMPLEX MEASUREMENT, FRANK TALKED ABOUT BUILDING A COMPOSITE TOOL BEHAVIORAL TOOL SOME SORT OF QUESTION THAT CAPTURES AS MUCH AS YOU CAN BUT THE FUTURE WE INTEGRATE ALL THREE DATA MODALITIES. BEHAVIOR DATA SET SOCIAL DATA SETS AND BIOLOGICAL DATA SETS. THE WAY TO THINK ABOUT THAT AS A DATA SCIENTIST IS TO THINK ONE OF THE WAYS IS TO THINK STRUCTURAL DATA VERSUS UNSTRUCTURED DATA. SO A LOT OF WHAT WE TALKED ABOUT SO FAR IS STRUCTURED DATA. DATA THAT CAN BE DIGITIZED. WE ALSO HAVE A HUGE VOLUME OF UNSTRUCTURED DATA, IN THE FORM OF PATIENT INTERACTION IF YOU WILL, BUT IF WE CAN BUILD TOOLS TO INTEGRATE THIS DATA DIFFERENT MODALITIES OF DATA, THEN TO EXTRACT FEATURES, THERE ARE TOOLS AVAILABLE NOW. FROM DEEP LEARNING AND NEURAL NETWORK. WE CAN EXTRACT THE DATA, THESE FEATURES AND POTENTIALLY BUILD HIGHER ORDER MODELS AND THEN TO COME UP WITH SOMEWHAT COMPLEX BIOSIGNATURE THAT IS CONTEXT DRIVEN. THAT PERHAPS IS THE FUTURE. AND PERHAPS IS THE GOAL WE CAN ACHIEVE (INAUDIBLE) THAT'S WHAT I HAVE IN MIND. SO TIME TO THINK ABOUT IS SOMETHING TO THINK ABOUT IN TERMS OF PAIN. ANY NEUROLOGIC PROCESS INTERFACE OF ALL THIS THREE MODALITIES AND FUNNEL THROUGH USE DATA SCIENCE TO BUILD A COMPLEX SET OF MEASUREMENTS. >> THERE HAS BEEN RESEARCH ON ANIMAL MODELS OF EMPATHY AND SOCIAL INTERACTIONS SO ARTICLE IN SCIENCE FROM JEFF'S LAB SHOWING ANIMAL RAT DEMON INVESTIGATING EMPATHY SO IN FACT FOR OTHER INJURED ANIMAL, IN FACT IT WOULD BE POSSIBLE TO TRY TO DO ANIMAL MODELS THAT MIGHT BRING MANY THE CONCEPT OF SOCIAL THAT BOTH OF YOU HAVE TALKED ABOUT. LET ME CLOSE DOWN THE SPEAKER PART OF THIS AND NOW OPEN IT UP TO THE ALL OF YOU WHO HAVE BEEN SO PATIENTLY WAITING FOR LAST TWO DAYS JUST TO GET HERE, AND OPEN IT FOR DISCUSSION. NOT NECESSARILY OR SPECIFICALLY TO ANY OF THE THREE OF US JUST PULLING AT THE OTHER BUT THE WHOLE MEETING WHAT YOUR THOUGHTS OR TAKE AWAY, IDEAS ON THE GENERAL IDEA OF WHERE TO WE GO, BASICALLY WHERE DO WE GO FORWARD WITH THIS. TONYA, SEE YOUR HAND IS JUMPING UP. >> TWO THINGS I WANT TO COMMENT ON. ONE IS THAT THERE ARE A LOT OF CHRONIC CONDITIONS WHERE I THINK WE HAVE DONE A GOOD JOB OF SCREENING FOR PSYCHOSOCIAL DISTRESS, CANCER IS A GOOD EXAMPLE, THERE IS GUIDELINE SCREENING PSYCHOSOCIAL DISTRESS IN EVERY CANCER PATIENT. CYSTIC FIBROSIS IS ANOTHER EXAMPLE. EVERY CHILD IS SCREENED FOR DEPRESSION. AND QUALITY OF LIFE ACTUALLY. WOULD BE GREAT TO THINK HOW EFFORTS ARE DIRECTED SCREENING IN CHRONIC PAIN, WE WOULD AGREE CHRONIC PAIN PATIENT SHOULD HAVE A SCREENING FORE PSYCHOSOCIAL DISTRESS, WHETHER WE COULD TALK ABOUT THAT AS AN OUTCOME OR INSULIN FACTOR NONETHELESS EVERY PATIENT SHOULD BE SCREENED. SO THAT WAS JUST ONE THOUGHT WE CAN LEARN FROM SOME OTHER AREAS. THE SECOND IS IT WOULD BE REALLY TREMENDOUS IF WE HAD A LONGITUDINAL COHORT STUDY THAT HAD AN INTENTIONAL GOAL OF STUDYING PAIN, PAIN IS ADDED TO SOME POPULATION BASED STUDIES BUT IT'S NOT BEEN THE GOAL EVER. AND AGAIN THINKING OF THIS ACROSS LIFESPANS AN INTENTIONAL APPROACH TO HOW DO WE STUDY PAIN EARLY ON AND HOW DO WE FOLLOW PEOPLE OVER TIME. BOTH FOR UNDERSTANDING COURSE OF CHRONIC PAIN BUT ALSO UNDERSTANDING A LOT OF MEASUREMENTS HOW WE CAN MEASURE THIS PHENOMENON OVER TIME. >> SO MY ONE WORD IF YOU WERE PICKING WORDS, VARIABILITY JUST AS WE ARE KEEP COMING TOWARDS LIKE WE WANT A SIMPLE MEASURE, IN TENSION BETWEEN COMPLEXITY AND SIMPLICITY, I WOULD ALSO ENCOURAGE US ALL TO NOT ALWAYS LOOK AT MEAN RESPONSE. THAT'S ALWAYS -- HOW ALL OUR STATISTICS ARE BUILT. WE ARE ALWAYS LOOKING AT THE MIDDLE. THE MEAN EFFECT. I DON'T KNOW JUST ONE THING TRAINING PEOPLE ON A DAILY BASIS IN THE OR, I TAKE CARE OF ONE PERSON AT A TIME, I'M LIKE 100% FOCUSED ON THEM. AND THING THAT'S SO STRIKING IS HOW DIFFERENT PEOPLE ARE FROM EACH OTHER. THEY ARE SO DIFFERENT WHEN TRYING TO TITRATE IN AND TREAT HAIR PAIN IN REAL TIME. WE CERTAINLY FOUND THAT WITH ALL OF OUR RESEARCH THAT THERE'S A TREMENDOUS VARIABILITY IN THE PAIN OUTCOMES IN EVERY OUTCOME. EVERY MODULATOR. SO IF WE CAN JUST KEEP THAT IN MIND AND RESIST THE TENDENCY TO TRY TO LIKE COLLAPSE EVERYONE TOGETHER. IT'S SUPER HARD BUT IT IS IMPORTANT. >> YOU ARE ASKING A QUESTION BUT ONE OF THE WHEN ASKING MEAN DATA OR HAVING NORMATIVE DATA HE TALKED ABOUT GIVEN THE LONGITUDINAL WITHIN SUBJECT DATA, THAT IN SOME SENSE ALMOST OBVIATE IT IS NEED FOR NORMATIVE DATA BECAUSE YOU HAVE THE INDIVIDUAL SUBJECT PATIENT AS HIS OR HER OWN CONTROL, HIS OWN NORM IF YOU WILL. >> TOTALLY AGREE. >> THAT BECOMES A QUESTION TO YOU, DO YOU THINK IT WOULD AMELIORATE PROBLEM WITH VARIABILITY YOU ARE HIGHLIGHTING. IF SOMEONE IS OWN CONTROL, WHAT CHANGE YOUR PRACTICE FOR INSTANCE? RESEARCH WE TRIED TO LOOK AT PEEP LONGITUDINALLY, THAT'S ONE OF THE THINGS -- PEOPLE LONGITUDINALLY THAT'S ONE THING THAT'S INTERESTING BUT MORE AS KIND OF AS A GROUP OF RESEARCHERS FOR PEOPLE WHO TREAT PEOPLE JUST TO CONSTANTLY RECOGNIZE THAT AND IF THERE'S ANYTHING WE CAN TAKE TO OUR CLINICAL COLLEAGUES LIKE YOU WERE SAYING, FRANK, SOMETHING WE CAN EDUCAT PEOPLE ABOUT, IS THAT PEOPLE ARE DIFFERENT. I AGREE, IF WE USE EMA TYPE OF DATA, VERY RICH DATA SETS PEOPLE COULD COMPARE THEMSELVES TO HOW THEY WERE IN THE PAST. THAT WOULD START A MEANINGFUL CONVERSATION BETWEEN PATIENT AND DOCTOR TO REFLECT ON THAT. COUPLE OF PEOPLE MENTIONED THAT >> VARIABILITY ISSUE IS IMPORTANT. DIDN'T GET TO MENTION IT >> SO THE CLUSTER THE TENDENCY TO CLUSTER IS LIKE A SNEAKY WAY OF TRYING TO GET BACK TO THE MAIN -- IN A WAY, WE STILL WANT TO COME BACK TO THESE DIGESTIBLE GROUPS. WHICH IS OF COURSE WE HAVE TO DO THAT TO CERTAIN EXTENT BUT RECOGNIZE THAT THAT -- YEAH, WITHIN A GROUP. >> THE VARIABILITY IS THE HOMOGENEITY SET UP, IF YOU ROCK AT MEASURES, THE ERROR BARS THOUGH THE NUMBERS ARE FEWER, WE FIND THAT THERE'S VERY TIGHT -- MUCH LESS VARIANCE WITHIN THOSE MEANS FOR ALMOST ANY MEASURE. FOR LEE CLUSTERS COMPARED TO THE ENTIRE POPULATION. ACTUALLY ONE THING THAT'S ALLOWED US TO DO IS TO SEE SIGNALS IN OUR GENETIC VARIABLES BECAUSE THE PHENOTYPIC VARIANT IS LESS BY CLUSTER. SO WE SEE THAT THE HOMOGENEITY TAKING LARGE POPULATION AND BRINGING IT INTO MORE HOMOGENOUS POPULATIONS ACTUALLY THE VARIANTS WITHIN THOSE CLUSTERS IS LESS IS WHAT WE HAVE SEEN. >> THAT WOULD SEEM IMPORTANT FOR THAT MESSAGE TO GET, WHEN WE START IDENTIFYING CLUSTERS WEIGHT AND CLASS ANALYSIS, ALL THESE VARIATIONSSH IT GOES BACK TO THE OLD DAYS WHEN YOU DICHOTOMIZE, HIGH OTHER LOW MEANT SOMETHING SO FIE PRO MYIAL GEEIA IT HAS POINTS YES AND NO. WE WENT TO USE THE TESTS. EVERY TIME YOU PRESS ONE OF THESE DESIGNATED LOCATIONS YOU ASK TO RATE PAIN FROM 0 TO 10 ON THE SCALE YOU GET POTENTIAL SCORE FROM FIBROMYALGIA PATIENT 180 AS PERSON RATINGS WOULD BE EQUAL TO 120 COMPARABLE TO PERSON WHO SAYS IT'S 11. BOTH OF THEM MEET -- MET CRITERIA FIBROMYALGIA, THERE IS HETEROGENEITY IN THERE TO EXTENT YOU CAN DEMONSTRATE IT'S GREATER BETWEEN OR WITHIN THAT'S IMPORTANT. POINT TO MAKE. >> YIELD MY TIME TOWING WHO IS PATIENTLY WAITING. I WANT TO JUMP IN WITH CLUSTER BUT SOME POINT MAKE A FEW GENERAL COMMENTS >> I HAVE A QUESTION ALL OF YOU TALKING ABOUT CHALLENGE THE PROBLEM IS WHERE YOU WOULD LIKE TO HAVE. AND THERE'S A TALK REALLY REAM FOR SOMETHING ELSE ALMOST COMPLETELY IRRELEVANT BUT MIGHT BE USEFUL FOR US TO THINK ABOUT CURIOUS THE HEAR YOUR THOUGHTS. I HAVE KIDS AND EDUCATION AN PUBLIC SCHOOL, THEY HAVE A MATH TEST THREE TIMES A YEAR, EVERYBODY GOES THROUGH IT, READING AND MATT YOU TEST SO EVERY TIME YOU GET ONE SCORE, SOMEWHERE BETWEEN 0 TO 350 PARENTS HAVE NO CLUE, I KNOW MY KIDS NUMBER BUNS I ASK WHAT THE NUMBER MEANS THEY SEND A PACKAGE OF MY KIDS AND YOU BREAK IT DOWN TO DOMAINS AND SKILLS, EACH SKILL THEY HAVE A SCORE 0 TO 350. MY KIDS ARE GOOD AT THIS, BAD AT THAT, MAYBE I SHOULD HELP THEM THINGS THEY ARE BAD AT. YOU HAVE A SCORE AND YOU HAVE PROFILE VERY DIFFERENT DOMAINS THAT WILL GIVE YOU THINGS GOOD AND BAD AT TO DEVELOP STRATEGIES TO INTERVENTION. PATIENT WASH ABOUT CURRENT SWIG, WHAT IS THE PROTOCOL MARKERS (INAUDIBLE) >> I THINK AS I TALKED ABOUT YESTERDAY, IT DIFFERS FOR EVERYONE. THERE ARE KEY DOMAINS THAT PATIENTS HAVE CONTINUALLY EXPRESSED AS IMPORTANT, THEIR ABILITY TO FUNCTION PARTICIPATE IN SOCIAL ACTIVITIES. THEN I THINK FOR EVERYBODY AGAIN THOSE FUNCTIONAL GOALS ARE GOING TO BE DIFFERENT, FAIRLY COMPLEX. (INAUDIBLE) WE TALKED ABOUT -- >> I DON'T THINK THAT I CAN APPROXIMATES THAT BECAUSE I DO THINK IT IS INDIVIDUAL AND DIFFERENT FOR EVERYONE, IT'S INTERESTING THE DATA THAT BILL YOU PRESENTED FROM ARTHUR THAT SHOWED IT'S NOT JUST THE WORST PAIN FOR PATIENTS, BUT THE AM OF TIME THEY ARE IN THAT AMOUNT OF PAIN. HOW MUCH ARE YOU IN AN 8. I DON'T THINK THAT'S A SOMETHING THAT I HAVE EVER SEEN REPORTED BEFORE. >> IT ISN'T ROCKET SCIENCE, THERE ARE WAYS TO THERE IS A TECHNIQUE CALLED GOAL ATTAINMENT SCALING. THERE'S WAYS TO TAKE GOALS PATIENTS ARTICULATE RELATED TO PAIN, THIS IS DONE IN THE PAIN AREA. THAT PARTICULAR GOAL AND THEN USE THAT METRIC OR CAUSE TREATMENT TO TRACK PROGRESS. USING OUTCOME IN SOME PAIN MEASURES SO THERE ARE WAYS TO GET THAT PERSPECTIVE INTEGRATED, CERTAINLY THEY CAN BE IMPROVED AND SO ON. BUT IT'S NOT SOMETHING THAT IS IMPOSSIBLE. >> RELATED TO THAT, I THINK KRISTEN YOU HAD IN YOUR SLIDES THE ONLY PLACE I HAVE SEEN RECOVERY EXPECTATION. I CAN'T REMEMBER WHO HAD IT. SOMEBODY HAD IT IN A SLIDE. IT HIT ME AS SOMETHING THAT WE DON'T TALK ABOUT VERY MUCH, WE DON'T MEASURE VERY WELL. BUT PATIENTS PROBABLY -- THIS IS ANECDOTAL EXPERIENCE FROM MY PAIN EXPERIENCE PRETTY CRITICAL, IT'S ONE THING TO BEAR WHEN YOU THINK THE NEXT FEW MONTHS IT WILL GET BETTER VERSUS THIS IS WHAT I AM GOING TO LIVE WITH THE REST OF MY LIFE. >> THERE'S BEEN SOME RESEARCH IN THE ARTHRITIS LITERATURE, NICK BELLAME TRYING TO LOOK FROM A PATIENT PERSPECTIVE WHAT WOULD BE A MEANINGFUL IMPORTANT CHANGE TO HIM OR HER. HE DEVELOPED A MEASURE BUT I DON'T KNOW IF YOU HAVE SEEN IT. DO YOU KNOW ABOUT HIM AND -- SOMETHING ABOUT THERE ARE AT LEAST ONE EFFORTS AT LEAST IN -- NICK WAS IN THE FUNCTION OF WHAT'S IMPORTANT. WHAT IS MEANINGFUL AND IMPORTANT. SO UNFORTUNATELY IT COULD BE DISEASE SPECIFIC FROM THAT CIRCUMSTANCE. >> SIMILAR QUESTION I HAVE TO THAT, IS THAT WE GRAPPLE WITH THIS A BIT IN THE MATERNAL HEALTH SPACE LOOKING AT ADVERSE MATERNAL EVENTS. A LOT OF WOMEN I GUESS THE QUESTION WOULD BE HOW ARE PATIENTS ABLE COMMUNICATE THEIR LEVEL OF PAIN SO THAT THERE'S SOME TYPE OF CONSISTENCY ACROSS PATIENTS. SO SOME WOMEN EXPRESS OR A LOT EXPRESS I FELT LIKE I WAS ABOUT TO DIE. AND THEY DON'T KNOW HOW MUCH IS NORMAL AND SOME PEOPLE DON'T RETURN TO THE ER OR RETURN TO HOSPITAL, BECAUSE THEY DON'T -- THINK THINK THIS IS NORMAL, I THIS WAY AND WIND UP EXPERIENCING A SEVERE MORBIDITY EVENT. WHEREAS MAYBE THEY HAVE BEEN TOLD THAT THAT'S NORMAL. THAT LEVEL OF PAIN IS NORMAL. HOW DO YOU COMMUNICATE OR PATIENTS ABLE TO COMMUNICATE THE SEVERITY OF A LEVEL OF PAIN AND UNDERSTAND WHAT DIFFERENCE LEVELS OF PAIN ARE EXPECTED AND NOT EXPECTED. I THINK THAT'S A SIMILAR TO YOUR QUESTION, BUT A DIFFERENT TYPE OF MEASUREMENT OF PAIN FROM A PATIENT PERSPECTIVE. AND WHAT'S TO BE EXPECTED. >> WE WERE DISCUSSING WHEN YOU GO TO DOCTOR OR KID GOES TO DOCTOR AND THEY SAID THIS IS GOING TO PINCH. WHAT DOES THAT MEAN? AND HOW DO PEOPLE RESPOND TO THAT. AND IF YOUR EXPERIENCE IS DISPROPORTIONATE TO WHAT DOCTOR TOLD YOU, IT MAY LEAD TO SOMETHING VERY DIFFERENT THAN IF IT'S LESS, IF I TOLD YOU IT WOULD BE BAD AND IT WASN'T SO BAD, OH HEY THAT WAS GOOD. I MIGHT REMEMBER POSITIVELY. SO THE INFORMATION GIVEN TO THE INDIVIDUAL, SOME OF THESE QUESTIONNAIRES, WHAT WE SAY AND HOW WE PHRASE QUESTIONS TO THE PATIENT OR TO THE SUBJECT BECOMES REALLY IMPORTANT THEY DON'T ALWAYS UNDERSTAND THE SAME WAY WE THINK WE'RE TELLING THEM AND WE NEED TO PAY ATTENTION TO KRISTIN -- THE DATA FROM HER SURVEY AND OTHER PATIENT ORIENTED SURVEYS TO HELP US UNDERSTAND WHAT PATIENTS PEOPLE FOCUS GROUPS AT FDA STRONGLY ENCOURAGES ON DIFFERENT QUESTIONNAIRES IS PERCEPTION FROM THE PATIENT. I MENTIONED YESTERDAY CATATRAPHIZING. THEY HATE THAT TERM, HAY VIEW IT PEJORATIVE AND IT'S ALL IN MY HEAD STUFF SO WE NEED TO LISTEN TO THE PATIENTS. OBVIOUSLY THE FDA IS DOING THEIR PATIENT FOCUSED TREATMENT, THE OTHERS ARE DOING. I'M SORRY NOT LOOKING THIS WAY. >> IT'S FINE. ONE PERSPECTIVE THAT MISSING A LITTLE BIT AND I THINK WOULD BE HELP US ALL AS RESEARCH COMMUNITY IS THE CONCEPT OF MUCH MORE STANDARDIZED DATA BUT WHAT DO YOU DO WITH THAT. SHARING WOULD BE OPTIMAL. THAT WAY WE COULD ADDRESS THINGS LIKE ARE THERE RACIAL DISPARITIES. I CAN ONLY RECRUIT 30 PATIENTS WITH SPINAL CORD INJURY IN A YEAR AT BEST. I'M NOT GOING TO STRATIFY THOSE INJURY. ELIZABETH AND I HAVE SIMILAR PROTOCOLS AND WE SHARE THAT DATA, YOU CAN GO INTO CATATRAPHIZING VERSUS SPINAL CORD INJURY. THAT'S ALSO COMING FROM ABOVE THAT DATA COLLECTED WITH FEDERAL FUNDING SHOULD SOME POINT LOOK AT THE LOWEST HANGING FRUIT, IN OUR OWN PUBLICATIONS BUT THEN WE SHARE THAT OPENLY AND AS EFFICIENTLY AS POSSIBLE. I THINK THAT WOULD GIVE US A -- >> IS THIS ENOUGH HAVE INITIATIVES ON THIS? >> WE TO. AND WE KEEP PUSHING THAT BILL HAS GENERAL POINTS ADS WELL. THERE IS NO DATA REPOSITORY AMONG PAIN RESEARCHERS AT THIS POINT IN TIME OR THERE IS? >> USUALLY MORE GENERIC ONES FOR >> IN TERMS OF IMAGING THERE'S A COUPLE OF DEPOSITORIES BUT WE ARE NOWHERE NEAR WHAT AUTISM OR ADHD OR ALZHEIMERS HAVE DONE, THEY STARTED AHEAD OF US. WE CURRENTLY -- I MEAN WE CAN ALWAYS PUT STICKS OUT THERE BUT WE ALSO NEED TO GIVE THE CARROTS AND RESOURCE US TO DO IT ADS WELL. >> WE ARE WINDING DOWN SO HERE IS YOUR IMPORTANT OPPORTUNITY THE TELL US WHAT IT IS. >> YOU MAY COME OVER HERE AND USE MINE. >> JUST A COUPLE OF GENERAL THOUGHTS AND COMMENTS. I THINK BACK OVER MY YEARS IN SCIENCE AND OTHER GROUPS THAT HAVE MADE GREAT HEADWAY OVER THE YEARS, ESPECIALLY HEART LUNG AND BLOOD IN CARDIOVASCULAR DISEASE. WHAT ARE SOME OF THE DIFFERENCES BETWEEN THE PAIN COMMUNITY WE HAVE COME FROM AND HEART LUNG AND BLOOD AS AN EXAMPLE. TO ME ONE OF THE BIGGEST DIFFERENCES IS THAT THEY HAVE SPONSORED EXPENSIVE BUT THEY HAVE SPONSORED VERY LARGE COHORT STUDIES. FROM WELL DESIGNED CONSENSUS DURING THE DEVELOPMENT OF THOSE STUDIES, FOR HOW THE QUESTIONS, THE AIMS AND HOW THINGS ARE GOING TO BE MEASURED. SO I GO TO TONYA'S RECOMMENDATION, I ALSO AGREE AND HAVE FOR SOME TIME, THAT'S WHY WE GOT INTO OPERA, WE FELT LARGE COHORT STUDIES LONGITUDINAL IN NATURE WILL PROVIDE A HUGE AMOUNT OF INFORMATION, THAT IS ACTIONABLE TO THE CLINIC. I THINK OPERA HAS BEEN A VERY GOOD EXAMPLE OF THAT POSSIBLE OUTCOME. THERE NEEDS TO BE MORE OPERA LIKE INITIATIVES IN MY VIEW. THAT DOESN'T EXCLUDE BASIC SCIENCE WITHIN THAT. I THINK ONE WAY TO BEGIN TO OPERATIONALLIZE HEART LUNG AND BLOOD-LIKE INITIATIVES, IS TO CONSIDER VIRTUAL CENTERS VIRTUAL PAIN CENTERS MAYBE SOMETHING LIKE THE HUB AND SPOKE SYSTEMS THAT ARE OUT THERE LIGHT NOW FOR OUR THERAPEUTIC TRIALS. BUT A WAY IN WHICH WE CAN INTEGRATE THE COMMUNITY, PROVIDE THE DATA SHARING PROVIDING CONSTRUCTS WE WANT TO MEASURE, I TOTALLY AGREE WITH FRANK, SOCIAL CONTEXT WHICH IS PART OF THAT Y AXIS ON MY X Y SLIDE BUT OTHER ENVIRONMENTAL INFLUENCES NEED TO BE HIGH PRIORITY IN THE DEVELOPMENT OF TRIALS. OF LONGITUDINAL STUDIES. SO WE HAVE DONE A WONDERFUL JOB WITH SMALL COHORTS AND IDENTIFYING SOME OF THE TIPSIFIES BEARINGS, BUT IF WE ARE GOING DEEP, AND IF WE HAVE MONEY COMING FORWARD THE NEXT DECADE FROM CONGRESS, I THINK ONE VERY IMPORTANT FEATURE SHOULD BE THINKING ABOUT MIMICKING WHAT'S BEEN SUCCESSFUL& IN HEART LUNG AND BLOOD WITH THE PAIN FIELD. I WANT TO RE-EMPHASIZE WITH THAT CONCEPT AS NOT EXCLUDE THE BASIC SCIENTIST BECAUSE WHEN YOU SEE A PHENOTYPE OF INTEREST IN THE PAIN SPACE, CLINICAL PAIN SPACE, AND IF YOU WANT TO ACT ON THAT WITH THERAPIES, IT'S IMPORTANT TO CAPITULATE THAT PHENOTYPE IN ANIMAL MODELS, AND MODIFY IT WITH POTENTIAL DRUGS THAT COMPLETELY TAKEN BACK TO THE CLINICAL SETTING. SO THERE IS A DISCONNECT IF WE DON'T ENGAGE BASIC SCIENTIST LOOK AT MECHANISMS BY WHICH WE BEGIN TO SEE FACTORS IN THE CLINICAL COHORT STUDY. >> I WILL TAKE THE LAST SIX MINUTES AND TURN IT BACK TO OUR ORGANIZERS AND WHAT'S THEIR TAKE AWAY, WHAT ARE THEY PICKED UP, WHAT WILL THEY WANT TO FOLLOW FORWARD ON. I WANT TO -- I GOT A GRAND TOTAL OF SIX MINUTES TO TELL US THE TRUTH ABOUT WHERE THEY -- WHAT THEY HAVE EXTRACTED FROM THIS AND WHAT THEIR NEXT STEPS ARE GOING TO BE. >> >> TALK ABOUT COMPLEXITY. I THINK -- I WANT TO CERTAINLY THANK EVERYBODY FOR THE LAST DAY AND A HALF. BECAUSE WE GAVE YOU AN UNUSUAL CHARGE. WE BROUGHT TOGETHER DIFFERENT PERSPECTIVES, AS WE HAD THOSE CALLS, THOSE PLANNING CALLS. I HEARD THEMES OVER AND OVER ABOUT I'M NOT SURE WHY I'M ON THIS SESSION. NOW I HOPE YOU CAN SEE. WHAT WE WERE THINKING AND WHY WE WANTED TO BRING THESE DIFFERENT PERSPECTIVES TOGETHER. WHAT WAS REALLY IMPORTANT TO US AND WE WILL BE FOLLOWING UP WITH ALL OF YOU IS TRANSLATING SOME OF THIS INTO ACTION ITEMS, THEY MAYBE THINGS THE NIH CAN CONSIDER, MAYBE THINGS OTHER AGENCIES CONSIDER, MAYBE THINGS THAT OUTSIDE THE GOVERNMENT CAN ALSO CONSIDER. WE CERTAINLY WANT TO BRING THESE PERSPECTIVES TOGETHER IN SOME KIND OF DOCUMENT, WE TALKED ABOUT WE WILL CERTAINLY HAVE A SUMMARY OF THIS, WE CAN EXPLORE HOW WE CAN BEST DISSEMINATE THIS INFORMATION, DOES THIS MEAN PUBLICATIONS, WHO WOULD WANT TO BE INVOLVED, DOES THIS MEAN PRESENTING THIS AT DIFFERENT ACADEMIC SOCIETIES OR OTHER SORT OF ORGANIZATIONS. WE CAN THINK ABOUT IT BUT WHOA IS CRITICALLY IMPORTANT TO US IS THAT THERE ARE ACTION ITEMS THAT COME OUT OF THESE TWO DAYS. IT IS CERTAINLY INTERESTING AND IS PROVOCATIVE AND ALL OF US WILL TAKE AWAY CERTAIN MESSAGES HOW WE DO OUR OWN WORK. WE WANT TO BRING TOGETHER TO PISH THE FIELD, TO MOVE THIS OUR DESCRIPTION IS NEXT GENERATION. WHAT DO WE DO. THERE'S A NUMBER OF THEMES THAT COME UP, YOU CAN SEE PAPERS IN FRONT OF ME, NOTES, THINGS WE CAN THINK ABOUT, WHO WE CAN REACH OUT TO TO INTEGRATE SOME OF THESE COMMENTS, IT'S BEEN VERY HELPFUL. THANKS TO ALL OF YOU FOR THE TIME AND THAT YOU PUT INTO THIS. LISTENING AND RESPONDING AND I ALWAYS FEEL AT THE END OF THESE MEETINGS THAT I DIDN'T HEAR DISCUSSION AS MUCH AS I WOULD LIKE TO HEAR DISCUSSION. AND SO THAT'S THE INVITATION THAT IF THERE WERE THINGS YOU WANTED TO SAY THAT YOU DIDN'T SAY YOU KNOW WHERE I AM, WHERE TO FIND ME, WHERE MY EMAIL IS. FEEL FREE TO WENDY OR ME OR ANY OTHER NIH STAFF HERE, IF THERE ARE THOUGHTS ABOUT MOVING THIS FORWARD. I DID HEAR, I HAVE BEEN TRYING TO SEPARATE THEM A BIT, THERE ARE SOME POTENTIAL RECOMMENDATIONS HERE BROADER THAN MEASUREMENT OF PAIN. THERE'S SOME RECOMMENDATIONS HERE THAT ARE VERY PAIN MEASUREMENT FOCUSED. THAT'S WHERE WE WERE TRYING TO GO SO PART OF THIS IS GOING TO BE SORTING OUT THINGS THAT ARE CRITICAL IN THE PAIN MEASUREMENT SPACE. CERTAINLY THE CASE YOU GET A SENSE OF -- WE USE THIS WORD A LOT. WE GET THE SENSE THERE'S COMPLEXITY. I GET IT, I UNDERSTAND COMPLEXITY HERE. JFK SAID WE GO TO SPACE NOT BECAUSE IT'S EASY THING TO DO BUT BECAUSE IT'S THE HARD THING TO DO. THIS IS THE HARD THING TO DO. WE HAVE TO FIGURE OUT A WAY TO WRAP OUR HANDS AROUND THAT COMPLEXITY HOWEVER DIFFICULT IT IS. COME UP WITH SOME CONCEPTUAL MODEL THAT ALLOW US TO THINK BOTH BECURRENTLY HAVE BUT ALSO GAPS, IMENT NOT SURE WHAT THEY ALL ARE BUT NOT EXPECT TO DO THAT IN A SINGLE MEETING BUT THAT'S WHERE I'M TRYING TO THINK ABOUT WHERE WE NEED TO GO NEXT. AGAIN, THANK YOU ALL FOR YOUR INPUT. VERY HELPFUL.