I'M CHRISTINE GRADY CHAIR OF THE DEPARTMENT OF THE BIOETHIC AT THE NIH CLINICAL CENTER AND CO-CHAIR WITH MY COLLEAGUE HANK GREELEY THE NEUROETHICS DIVISION OF THE MULTIWORKING GROUP OF THE NIH BRAIN INITIATIVE. WE'RE HERE TO HAVE A WORKSHOP ON THE ETHICS OF RESEARCH WITH NEURAL DEVICES. THESE ARE BOTH INVASIVE AND NONINVASIVE. I WANT TO SAY A WORD WHERE WE'RE GOING THIS TODAY. SOME OF YOU ARE MEMBERS OF THE NEUROETHICS DIVISION AND SOME KNOW THE HISTORY. BASICALLY WHAT HAPPENED WAS THE NIH INSTITUTE DIRECTORS ALSO RUNNING THE BRAIN INITIATIVE I THINK INSPIRED BY THE PRESIDENT'S COMMISSION GRAY MATTERS REPORTS AND BRAIN 2025 SAID WE NEED SOMETHING TO THINK ABOUT THE NEUROETHICS AND STARTED THE MULTI-COUNCIL WORKING GROUP. WE'RE NOT THAT OLD AROUND SINCE 2015, ONE THING WE DID WITH KARA RAMOS' HELP IS REVIEW THE PERFORM PORTFOLIO. WE LOOKED AT THE ETHICAL ISSUES WE SHOULD BE THINKING ABOUT AFTER YOU LOOK AT THE PORTFOLIO. ARE THERE ISSUES THAT ARE AMENABLE TO NEUROETHICS RESEARCH AND THIRD IS ARE THERE AREAS WHERE ADDITIONAL GUIDANCE WOULD BE HELPFUL. SO WE DID THAT EXERCISE. WHAT I NOTICED WHEN I LOOK AT THE NOTES IS THE QUESTION OF THE ETHICS OF RESEARCH WITH INVASIVE AND NONINVASIVE DEVICES CAME UP IN ALL THOSE AREAS. IT CAME UP AS AN ISSUE WE NEEDED TO THINK ABOUT ISSUE WITH NEUROETHICS RESEARCH AND WHERE ADDITIONAL GUIDANCE WOULD BE HELPFUL. pTHE GOAL IS TO TRY TO TALK ABOUT THE ISSUES AND FOCUS IN ON THEM. WHEN I FIRST PROPOSED THE WORKSHOP I HAD AT LEAST TWICE AS MANY CAPTIONING TOPICS AND WE'RE TALKING ABOUT ISSUES VERY LARGE IN SOME WAYS. THE DAY IS STRUCTURED TO REVIEW THE STATE OF THE SCIENCE AND WE HAVE TWO WONDERFUL SPEAKERS TO TALK ABOUT INVASIVE AND NONINVASIVE DEVICES AND WE'LL HAVE THREE PANELS. THE FIRST WILL ADDRESS RISK AND INVASIVENESS AND ONE FOR CONSENT AND ONE POST-TRIAL RESPONSIBILITIES. VERY IMPORTANT ISSUES. AND HERE'S IMPORTANT POINTS WE NEED TO LOOK TO IN DOING RESEARCH OF THIS NATURE WE'RE PLEASED TO HAVE THE DIRECTOR. >> I WANT TO SAY HI TO EVERYBODY AND SET THE STAGE IN TERMS OF THE BIG PICTURE OF THE BRAIN INITIATIVE. THIS IS THE MOST EXCITING AND LARGEST NEUROSCIENCE PROJECT NIH HAS DONE AND HAS MULTIPLE COMPONENT ALL FOCUSSING IN UNDERSTANDING HOW CIRCUITS WORK IN THE BRAIN AND THERE'S BEEN A LOT OF PROGRESS. WE'VE BEEN RUNNING NOW ABOUT FOUR YEARS AND THE TECHNOLOGIES IN WAYS WE COULDN'T HAVE PREDICTED. SOME HAVE EXPLODED AND ALLOWED US TO DO THINGS WE COULDN'T DO WHEN WE STARTED. THAT'S THE LESSON WITH TECHNOLOGIES YOU DON'T EXACTLY KNOW WHICH ONES WILL START EXPLODING. YET THE ETHICAL ISSUES REQUIRE KNOWING WHERE THOSE WHICH TECHNOLOGIES ARE COMING AND GOING. IT'S SOMETHING YOU CAN'T PREDICT BUT HAVE TO PLAN FOR. IN THE BRAIN INITIATIVE FROM THE BEGINNING WE HAVE BEEN WORKING WITH CHRISTINE AND HANK AND THE DIVISION OF NEUROETHICS AS PART OF A MULTI COUNCIL WORKING GROUP TO GUIDE OUR SCIENCE. WE'RE TAKING A DEEP DIVE AND GUIDE FOR THE RESEARCHES. THERE ARE WAYS WE NEED TO DO HEAVY THINKING IN A MORE IMPORTANT WAY AND THIS IS IMPORTANT BECAUSE WE'RE INTO HUMANS ALREADY. A LOT OF THE OTHER TECHNOLOGIES ARE NOT IN HUMANS YESTERDAY THEY'RE IN MICE SO IF YOU'RE A MOUSE BE AWARE OF THE ETHICAL ISSUES. THOSE THINGS WILL COME TO HUMANS EVENTUALLY. IT'S IMPORTANT FOR THE TOPIC ITSELF AND SETS A PRECEDENCE HOW TO DEAL WITH OTHER ISSUES AS THEY COME UP IN DISCUSSION. I APPRECIATE THE WORK PEOPLE ARE DOING IN THE SPACE. IT'S A NEW SPACE FOR A LOT OF US AT NIH BUT AN IMPORTANT ONE AND I THINK WE'RE LUCKY TO HAVE YOU HERE TODAY AND THE EFFORT AND JAY CHURCHILL FROM NIH. I THINK IT'S GOING TO BE A GREAT DAY. I HAVE TO GO IN AND OUT FOR SOME WEIRD REASONS INCLUDING PLAYING A BASKETBALL GAME. >> WE NOW HAVE UNDER THE BRAIN INITIATIVE 80 HUMAN PROJECTS AND I LOOKED BACK ON MY NOTES. AS RECENTLY AS A YEAR AND A HALF AGO IT WAS LESS THAN 15. THE PROGRESS IS REALLY RAPID IN TERMS OF MOVING INTO HUMANS. THAT MAKES WHAT WE'RE TALKING ABOUT TODAY EVEN MORE PRESSING. BEFORE WE GO AROUND THE ROOM QUICKLY, HANK DUE WANT TO SAY ANYTHING? [OFF MIC] >> MAYBE WE CAN QUICKLY INTRODUCE OURSELVES AND HOPEFULLY EVERYONE CAN TALK LOUDLY. >> HOLLY LANSABY NATIONAL INSTITUTE OF HEALTH. [ALL OFF MIC] [OFF MIC] >> SO JUST A COUPLE LOGISTICS. HOPEFULLY YOU HAVE AN AGENDA. THERE'S SOME IN THE BACK. THERE'S NAME TAGS IN THE BACK AND COFFEE THAT MIGHT BE READY IN THE BACK AND SNACKS. WE WILL TAKE BREAKS DURING THE DAY. WE'LL HAVE AND THERE'LL BE LOTS OF DISCUSSION AND INVITE EVERYBODY TO BE AS ENGAGED AS POSSIBLE. WE'LL INTRODUCE DR. LISANBY TO TA TALK. WE'RE GLAD TO HAVE HER HERE. >> GOOD MORNING. SO IT'S REALLY A PLEASURE TO BE HERE AND MY TASK THIS MORNING IS TO INTRODUCE YOU TO THE FIELD OF INVASIVE NEUROMODULATION. WHEN WE TALK ABOUT NONINVASIVE NEUROMODULATION WE TALKED ABOUT ELECTROCONVULSIVE TECHNOLOGY AND TODAY WE HAVE TOOLS TO ALLOW US TO MODIFY NEURAL FUNCTION USING A VARIETY OF TYPES OF ENERGY TO THE BRAIN WITH MAGNETIC FEELS OR TMS AND THE MAGNETIC FEELS CAN BE USED FOR FOCAL SEIZURES. SOME TOOLS ARE IMPLANTED LIKE VNS AND DEEP BRAIN STIMULATION OR DBS AND APPLY IT TO THE SCALP. WE CAN APPLY ENERGY STRONG ENOUGH TO INVOKE A SEIZURE AND FOR TRANS CRANIAL CURRENT STIMULATION WE APPLY WEAK ELECTRICAL CURRENTS BELOW THE THRESHOLD FOR INDUCING A SEIZURE AND SOME CALLS NEURONS TO FIRE. MY TASK IS TO INTRODUCE YOU TO THE TOOLS ON THE SLIDE THAT ARE NOT NONINVASIVE AND REMOVE THE INVASIVE NEUROMODULATION IS ENERGY THROUGH THE SCALP TO CHANGE BRAIN FUNCTION. WE CAN COMPARE THE TOOLS IN AXES WHETHER THEY'RE SURGICAL OR ANESTHESIA IS REQUIRED OR INDUCE SEIZURES OR THERE'S A CONTACT BETWEEN AN ELECTRODE ISSUE OR ELECTRODELESS STIMULATION AND HOW FOCAL THEY ARE AND THE LIST IS GROWING AND MUCH OF THE WORK UNDERWAY IN THE BRAIN INITIATIVE IS ADDING TO THE TOOLS FOR INVASIVELY AND NONINVASIVELY CHANGING BRAIN FUNCTION. WHAT I'LL REVIEW IN THE NEXT HALF HOUR ARE WHY DO WE NEED THESE TOOLS. WHAT'S THE CURRENT STATE OF PRACTICE AND SCIENCE WITH THE TOOLS AND WHAT'S NEXT. STARTING WITH WHY WE NEED IT. THE CENTER FOR DISEASE CONTROL ANNOUNCED THE SAD STATISTICS THE RATE OF SUICIDE IN OUR COUNTRY IS RISING. THIS IS TRUE IN MEN AND WOMEN AND ACROSS MOST DEMOGRAPHIC GROUPS. THIS IS DESPITE THE FACT WE HAVE EFFECTIVE PSYCHO THERAPIES FOR TREATING DEPRESSION. THIS CONTINUES TO BE AN UNMET PUBLIC HEALTH WAYS AND FINDING WAYS TO IMPROVE PUBLIC HEALTH AND PREVENT SUICIDE. WE HAVE MEDICATIONS THAT ARE FDA APPROVED FOR THE TREATMENT OF DEPRESSION, HOWEVER, THE STAR D TRIAL SPONSORED BY THE NATIONAL INSTITUTE OF MENTAL HEALTH GAVE US THE SUPPORTING RESULT WHEN PATIENTS ARE EXPOSED TO THEIR FIRST ANTI-DEPRESSANT MEDICATION LESS THAN HALF RESPOND AND WHEN THEY SWITCH TO A THIRD AND FOURTH. THE PERCENT OF PATIENTS RESPONDING ONCE THEY'RE MEDICATION RESISTANT GOES DOWN. WE FIND WHEN WE CHANGE MEDICATIONS FROM ONE TO THE NEXT THERE'S DIMINISHING RETURNS IN TERMS OF DEPRESSION OUTCOME. THIS MEANS WE NEED EFFECTIVE ALTERNATIVES TO FIND THE RIGHT MEDICATION FOR PATIENTS. THIS LEADS ME TO AN INTRODUCTION OF WHAT IS THE CURRENT STATUS OF NON INVASIVE NEUROMODULATION FOR TREATING BRAIN-BASED DISORDERS. THIS HAS BEEN TRANSFORMATIVE. THE ABILITY TO CHANGE BRAIN FUNCTION HAS BEEN A WONDERFUL STIMULUS ALLOWS YOU TO MORE BEYOND CORRELATION BETWEEN BRAIN AND RELATIONSHIPS WHICH PHYSIOLOGY PROVIDES TO AN UDERSTANDING OF THE CAUSAL RELATIONSHIP BETWEEN BRAIN NETWORKS AND COMPLEX HUMAN BEHAVIORS. FOR EXAMPLE, YOU CAN DO HYPOTHESIS TESTING BY FOCAL INTERVENTION AND ASK WHAT FUNCTIONAL ROLE THEY PLAY. THIS HAS HELPED MOVED US FORWARD IN THE PATHOPHYSIOLOGY UNDERLYING BRAIN BAYED DISORDER IN NEUROLOGY. I'LL LOOK AT THE IMPACT NEUROMODULATION HAS HAD. WE HAVE EVIDENCE-BASED PSYCHO THERAPIES AND PHARMA PSYCHOLOGICAL APPROACHES AND NEUROKNOWLEDGELATION -- NEUROMODULATION APPLICATIONS. WE CAN APPLY UNPRECEDENTED POTENTIAL FOR OUR PATIENT. LET'S START WITH ECT. IT'S HIGHLY EFFECTIVE AND RAPIDLY ACTING IN TREATING THE MOST SEVERE CASES OF TODAY DEPRESSION. AND FDA APPROVED. I'M SHOWING THOSE IN REMISSION AFTER TREATMENT AND IN THE BAR THE PATIENTS RESPONDING. AFTER THE FIRST TWO WEEKS NEARLY HALF THE PATIENTS REMITT WHICH MEANS THEIR DEPRESSION IS IN THREE WEEKS CLOSE TO 80% ACHIEVED REMISSION. THIS IS A POTENT TREATMENT FOR OUR MOST SEVERELY DEPRESSED PATIENTS. WE'VE LEARNED OVER THE YEARS HOW TO IMPROVE THE SAFETY OF THIS TREATMENT SPECIFICALLY BY MOVING WHERE WE PLACE THE ELECTRIC FIELDS ON THE SCALP FROM THE BILATERAL ELECTROPLACEMENT ON THE TEMPLE TO REDUCE THE AMOUNT OF MEMORY LOSS. HERE ON THE Y AXIS IS AN AMNESIA SCORE FOR PERSONAL MEMORIES AND IMPERSONAL MEMORIES FOR FACTS ABOUT THE WORLD. FOR BILATERAL THE AMNESIA IS IN BLUE AND UNILATERAL IN RED. FOR BOTH TYPES OF MEMORY WE HAVE A SPARING OF MEMORY WHEN WE MOVE THE ELECTRODES TO SIMULATE THE PARTS OF THE SCALP. WHY? WE KNOW FROM ARRESTISTIC HEAD MODELLING WHEN YOU MOVE THE ELECTRODES YOU MOVE WHERE THE ELECTRODE IS BEING MOVED ON THE BRAIN. IT'S ELECTRIC FIELD STIMULATION WITH BILATERAL AND UNILATERAL ECT. YOU CAN SEE WE'RE SHIFTING WHERE THE CURRENT IS GOING AND BELIEVE THIS IS PART OF WHY WE HAVE DIFFERENT SIDE EFFECT PROFILE. THE SECOND INNOVATION IN IMPROVING THE SAFETY OF ECT HAS BEEN TO SHORTEN THE PULSE WIDTH. ECT IS GIVEN WITH SQUARE WAVES WHICH LAST ONE TO TWO MILI SECOND AND THIS REDUCES THE AMOUNT OF AMNESIA. THE DEEPER COLOR IS THE STANDARD PULSE WIDTH AND THE LIGHTER COLOR IS THE ULTRA PULSE WIDTH AND THERE'S SAVINGS IN TERMS OF LESS MEMORY LOSS. YOU PUT THEM TOGETHER UNILATERAL AND ULTRA BRIEF AND PROVIDES THE OPTIMAL INTERVENTION TODAY WITH ECT TO MAXIMIZE EFFICACY AND REDUCING SIDE EFFECTS. EXCITINGLY NOW WITH ADVANCES IN ENGINEERING WE HAVE LESS INVASIVE TECHNOLOGIES TO STIMULATE IT BRAIN WITHOUT INDUCING SEIZURE WITH TMS WHICH IS CLEARED FOR THE TREATMENT OF DEPRESSION. AND IN FACT THERE ARE A VARIETY OF DEVICES SINCE THE FIRST APPROVAL IN 2008. THIS ABILITY TO FOCALLY STIMULATE AREAS WITHOUT INDUCING A SEIZURE ALLOWS US TO LOOK AT THE FINDINGS OF DEPRESSION INTO CIRCUIT-BASED INTERVENTION AND TREATMENT. I THE CASE OF DEPRESSION, FOR EXAMPLE IT INVOLVES A NETWORK OF BRAIN AREAS INVOLVING PREFRONTAL CORTEX AND LIMBIC STRUCTURES AND CAN LOOK TO NODES IN THE NETWORK SUCH AS THE DORSAL PREFRONTAL CORTEX AND EFFECTIVELY TREATING DEPRESSION. THERE'S TWO TYPES OF COILS FOR TREATING DEPRESSION. ONE IS FOCAL CALLED THE FIGURE 8 COIL AND NON-FOCAL WHERE YOU PLACE IT INSIDE LIKE A HELMET. THERE'S MORE FOCAL APPROACHES SUCH AS DEEP BRAIN STIMULATION WHICH ALLOW YOU TO DIRECTLY ACCESS DEEPER TARGETS INACCESSIBLE TO TRANS CRANIAL ELECTROSTIMULATION AND ARE FDA APPROVED FOR CERTAIN NEUROLOGICAL CONDITIONS. THERE'S AN EXEMPT FOR THE USE IN THE TREATMENT OF MEDICATION REFRACTORY OBSESSIVE COMPULSIVE DISORDER OR OCD. I TALKED ABOUT THE FDA CLEARED PRODUCTS BUT THERE'S ALSO OFF-LABEL USE IS A REALITY IN OUR FIELD. TDCS THOUGH IT IS NOT FDA APPROVED FOR THE TREATMENT OF PSYCHIATRY AND NEUROLOGY IS SOMETHING OUR PATIENTS KNOW ABOUT AND YOU CAN GOOGLE THIS AND THERE ARE CLINICIANS THAT PRACTICE THIS IN AN OFF-LABEL BASIS AND A WEBSITE ADVERTISES THE USE FOR THE OFF-LABEL CONDITIONS AND THE CLINIC ADVERTISE HOME USE AND TRAIN YOU FOR USE AT HOME. THIS IS NOT STANDARD OF CARE OR AN FDA CLEARED MEDICAL PRACTICE. THEY'RE NOW BEING BUNDLED INTO WHAT ARE LIFESTYLE PRODUCTS BEING MARKETED FOR IMPROVING SPORTS PERFORMANCE OR IMPROVING THE PERFORMANCE IN GAMING BUT NOT FOR THE TREATMENT OF ANY MEDICAL CONDITION. BUT PATIENTS WITH FAMILIES ARE INCREASING UP THEIR PRODUCT AND BEGINNING TO USE THEM IN A VARIETY OF WAYS. THIS PRESS RELEASE THAT THE U.S. MILITARY IS DOING RESEARCH IN THE AREA AND THAT PRODUCTS ARE TRYING TO LEVEL THIS TO IMPROVE ATHLETIC PERFORMANCE. AND EVEN REPORTED OLYMPIC TEAMS TRIED THE PRODUCTS. SOME OF THE CLAIMS YOU'LL SEE ON THE WEB INCLUDE IMPROVING GAMING PERFORMANCE, ENHANCING ATTENTION, FACILITATING LUCID DREAMING AND ALL OF WHICH ARE NOT PART OF MEDICAL PRACTICE. THERE'S TWO COIL TYPES THE FIGURE 8 COIL AND THE H COIL ALSO CALLED THE HELMET COIL. EACH COILS HAVE A DIFFERENT GEOMETRY. THAT RESULTS IN A DIFFERENT DISTRIBUTION OF ELECTRIC FIELD IN THE BRAIN. THE FIGURE 8 COIL IS MORE FOCAL. THE H STIMULATES BROAD REACHES OF THE BRAIN AND THERE'S IS A CONCENTRIC MODEL IN THE HEAD. NOT ONLY DO THEY DIFFER DRAMATICALLY IN WHERE THE ELECTRIC FIELD IS BEING INDUCED WHICH IS THE SPACIAL DOSE BUT IN TERMS OF THE TEMPORAL ASPECT OF THE DOSING. IT REFERS TO THE FREQUENCY OF THE PULSES, DURATION OF THE PULSES. THOUGH THE COILS DIFFER DRAMATICALLY IN THE SPACIAL AND TEMPORAL COMPONENT THEY'RE ON THE MARKET FOR THE SAME INDICATION WHICH IS DEPRESSION. IT LEADS TO A RESEARCH GAP IN THE FIELD WE HAVE INSUFFICIENT KNOWLEDGE HOW TO OPTIMIZE THE DOSING AND WHAT ROLE THE DOZE OF THE ADMINISTERED INTERVENTION PLAYS IN TERMS OF CLINICAL OUTCOME. AND OUR TECHNIQUE IS RAPIDLY EVOLVING AS A RESULT OF RESEARCH. SO AS I MENTIONED THE OPTIMAL DOSE IS UNKNOWN BUT THE COMPONENT THAT DESCRIBE THE DOSE INCLUDE THE SPACIAL DISTRIBUTION OF THE DELIVERED DOSE WHICH IN THE CASE OF TMS IS CONTROLLED BY THE GEOMETRY OF THE COIL AND HOW IT'S HELD ON THE HEAD RELATIVE TO THE BRAIN. THEN THERE'S THE TEMPORAL ASPECT. HOW WE TUNE THE FREQUENCY AND THE PULSE SHAPE IN THE TIME AXIS AND THE CONTEXT OF USE. WHAT THE PATIENT IS DOING AT THE TIME THEY'RE STIMULATED. WHETHER THEY'RE ENGAGED IN A COGNITIVE TASK OR TAKING MEDICATION. ALL ASPECTS EFFECT THE STATE OF THE BRAIN INFLUENCE THE EFFECT OF THE STIMULATION ON THE BRAIN. WE UNDERSTAND THE TEMPORAL AND SPACIAL AND CONTEXTUAL INTERACTION. THIS INTRODUCED SOME EXPERIMENTAL APPROACHES OF A COMBINATION OF ENGAGING THE BRAIN IN A COGNITIVE TASK WHILE YOU STIMULATE IT. THIS IS CPAS AND IT IDEA IS TO OPTIMIZE THE STATE OF THE BRAIN WEN WE'RE STIMULATING IT. AS AN EXAMPLE WE USED FUNCTIONAL IMAGING TO GUIDE THE PLACEMENT OF THE COIL FOR WORKING MEMORY. WHEN WE HAVE THE SUBJECT PERFORM THE TASK AND RECEIVE THE STIMULATION THIS CAN IMPROVE WORKING MEMORY PERFORMANCE. NOW I'M MOVING TO OFF-LABEL WAYS OF USING THE TOOL AND ACTIVE RESEARCH. THAT'S A LEAD TO WHAT WE MIGHT EXPECT COMING NEXT IN THE FIELD OF NONINVASIVE NEUROMODULATION. WE TALKED ECT IN PSYCHIATRY. WE NOW HAVE EXPERIMENTAL APPROACHES AND WAYS TO INDUCE SEIZURES THAT IMPROVED FOCALITY. MAGN MAGNETIC STIMULATION TO INDUCE SMALL SEIZURE IF THE BRAIN TO IMPROVE THE RATIO OF THE TREATMENT. BY USING MAGNETIC INDUCTION WE'RE ABLE TO GET MORE FOCAL THAN CONVENTIONAL ECTs. YOU SEE THE CONVENTIONAL UNILATERAL PLACEMENT ON THE TOP AND MAGNETIC SEIZURE PLACEMENT ON THE BOTTOM. YOU CAN SEE THE FIELDS ARE SUPERFICIAL TO THE SCALP JUST UNDERLYING WHERE IT'S PLACED. IT INDUCES SEIZURES THAT ARE WEAKER AND MORE LOCALIZED. AND THIS SHOWS THE STRENGTH ON THE TOP AND MST ON THE BOTTOM. AND THESE WEAKER FIELDS AND WEAKER SEIZURES HAVE BEEN ASSOCIATED WITH LESS COGNITIVE DYSFUNCTION. I'M SHOWING A MEASURE OF VERBAL MEMORY BEING REDUCED AFTER CT IN THE BLUE AND NOT EFFECTED BY EST IN THE BLUE BAR. THEY DEMONSTRATED SUPERIOR OUTCOME WITHOUT SACRIFICING SUPPRESSANT BENEFIT. YOU SEE OUR RANDOMIZED DOUBLE-BLINDED CONTROL TRIALS SHOWING THE RESPONSE RATE WITH CONVENTIONAL ECT IN THE BLUE AND EST IN THE RED. THIS REFLECTS AN AREA BACK TO RESEARCH. THIS IS NOT AN FDA APPROVED INTERVENTION BUT WHERE SOME RESEARCH IS GOING. ANOTHER TECHNOLOGY IS CALLED TRANS CRANIAL DIRECT STIMULATION. OR TDCS. IT APPLIES DIRECT CURRENT TO THE SCALP VIA ELECTRODES ON THE SCALP. WE USE WEAK CURRENTS ONE TO TWO MILLIAMPS. HOW'S IT WORK? THERE'SANODE AND IT DEPOLARIZING AND THE CATHODE INHIBITS CORTICO FUNCTION AND IT RESPONDS WHEN STIMULATED VIA OTHER MEANS. THERE'S BEEN A VARIETY OF RANDOMIZED TRIALS WHETHER TDCS IS USEFUL IN DEPRESSION. THIS IS A METAANALYSIS SHOWING A SIGNIFICANT ANTIDEPRESSANT EFFECTS APPLIED ON THE SAME SIDE TMS IS APPLIED IN THE FDA CLEARED DEPRESSION TREATMENT. HERE'S THE REMISSION RATES WITH THE SHAN ON HE RED AND THE FD APPROVED ON ORANGE AND TDCS ALONE AND THE OTHER IS TDCS PLUS THE MEDICATION GROUP AND SHOWED ANTIDEPRESSANT BENEFIT. WE HAVE ACCEPTED FOR INTERNATIONAL A CONTROL TRIAL TRYING TO REPLICATE THE RESULT. IN THIS CASE WE USED TDCS WITH AN ANODE ON THE LEFT AND THE CANODE ON THE RIGHT AND USED 2.5 MI MILLIAMPS AND RAMP UPS IN THE CURRENT. WHEN YOU RAMP UP THE CURRENT THERE COULD BE SCALP STIMULATION AND THIS SHOWS WE'RE REACHING BROAD REGIONS OF THE LATERAL PREFRONTAL CORTEX. WE HAD THE DISAPPOINTING RESULT THERE WAS NO DIFFERENCE BETWEEN AC SIF AND SHAM IN THE STUDY. YOU SEE A DEPRESSION MEASURE THE RATING SCALE ON THE Y AXIS AND ON THE Y AXIS IS TIME IN TERMS OF WEEKS. THE BLUE DOTTED LINE IS THE SHAM. THE SHAM GROUP I AM PROVED -- IMPROVED AND WE THEN CROSSED EVERYONE TO ACTIVE TREATMENT AT THE END OF THE STUDY. THERE WAS A SIGNIFICANT DFFERENCE BETWEEN ACTIVE AND SHAM. THE SHAM WAS MORE EFFECTIVE THAN THE ACTIVE. WE LOOKED AT PATIENTS WITH UNIPOLAR DEPRESSION THAN BIPOLAR DEPRESSION AND WE FOUND TO DIFFERENCE BETWEEN ACTIVE AND SHAM IN EITHER GROUP. WE ALSO LOOKED AT WHETHER GENETIC POLY MORPHISMS MIGHT HAVE MODERATED THE RESPONSE AND IT DID NOT. IN SUMMARY, FOR THE EFFICACY OF TRANS CRANIAL STIMULATION SOME STUDIES HAVE BEEN POSITIVE AND SOME HAVE NOT BEEN INCLUDING OURS. THE DOSE RESPONSE RELATIONSHIP IS NOT KNOWN. WE INCREASED THE DOSE ABOVE WHAT BERNONI HAD DONE. WE DON'T KNOW WHETHER HIGHER CURRENTS ARE ALWAYS BETTER. WE'RE LOOK AT THE IMPACT OF ELEC ELECTRODE ARRAY. THIS IS SIMILAR TO THE MONTAGE WE USED. YOU CAN SEE IT'S REALLY NOT FOCAL. IT'S STIMULATING FAR REACHES AND YOU CAN GET THINGS MORE FOCAL BUT THERE'S ALSO OTHER MULTIELECTRODE ARRAYS AND SOME STUDIES MAY STUDY WHETHER THE MORE FOCAL ARRAYS MAY ALLOW IT TO BE THERAPEUTICALLY DERIVED AND YOU CAN USE HEAD MODELLING FOR THE ELECTRODE ARRAY AND APPLY AN OPTIMIZED ELECTRODE ARRAY AND THIS REFLECTS FUTURE WORK TO BETTER REFINE THIS INTERVENTION. IN SUMMARY, THE DOSE RESPONSE RELATIONSHIP IS NOT KNOWN. WE WERE WONDERING WITH THE SHAM GROUP WORKED BETTER. LET'S LOOK AT THE DIFFERENCES. HERE'S THE ACTIVE INTERVENTION 2.5 MILLIAMPS AND TWO WERE SHUT OFF WITH LESS THAN TWO MINUTES OF EXPOSURE. WHAT WE DIDN'T KNOW WHEN WE DID THE TRIAL WAS THE SHAM INTERVENTION ALSO HAD A CONSTANT CURRENT WITH A LOW AMPERAGE BUT IN THE TRIAL WE DID FIND THIS ELECTRICAL DOSAGE TO BE MORE EFFECTIVE IN TREATING DEPRESSION THAN THE OTHER. AND WE LOOK AT THE WAY IT AFFECTS BRAIN FUNCTION. WE DON'T HAVE CLINICAL TRIALS FOR A TARGETED ENGAGEMENT. STRATEGY WHERE YOU FIND THE TARGET ON IMAGING AND DESIGN THE STIMULATION PROTOCOL TO DIRECTLY REACH THAT TARGET. WE NEED DOSE FINDING CLINICAL TRIALS IN OUR CASE THE SHAM VERSUS ACTIVE WAS A DOSE-RANGING STUDY THOUGH WE DIDN'T REALIZE IT. THERE'S NO CONSENSUS ON WHAT IS THE BEST BIOLOGICALLY SHAM TO USE. THE PARAMETER SPACE IS INFINITE AND RELATIVELY WELL EXPLORED AND YOU MAY GIVE A COGNITIVE INTERVENTION TO STIMULATE TO LOOK AT THE STIMULATION AND CONTEXT TO SCOPE CONNECTIVITY AND WE HAVE INSUFFICIENT UNDERSTANDING OF THE DRIVERS BETWEEN THE INDIVIDUAL DIFFERENCES. WE KNOW FROM NEUROSCIENCE STUDIES SOME HAVE INHIBITORY EFFECTS AND WE DON'T KNOW WHAT EFFECT IT WILL PLAY. MUCH OF THE WORK HAS FOCUSSED ON THE QUESTION, DOES IT WORK FOR, BLANK. BY IT I MEAN NEUROMODULATION AND FOR BLANK DOES IT WORK FOR DEPRESSION, ANXIETY, MOVEMENT DISORDERS AND SO ON. ARE WE ASKING THE RIGHT QUESTIONS? INDEED MANY OF OUR RESEARCH GAPS ARE TRYING TO ADDRESS THE DIFFERENT QUESTION WHICH IS HOW DOES IT WORK THE MORE WE KNOW ABOUT HOW IT WORKS WE MAY BE BETTER ABLE TO INTELLIGENTLY APPLY IT TO DEVELOP TREATMENTS FOR OUR MEDICATION-RESISTANT DISORDERS. THAT'S THE FOCUS OF THE BRAIN INITIATIVE TO FILL THE RESEARCH GAPS IN MECHANISMS AND DOSE-RESPONSE RELATIONSHIPS. I'M SHOWING THE CURRENT FUNDING OPPORTUNITY ANNOUNCEMENTS TARGETED TO THE NEUROMODULATION SPACE TO TALK ABOUT TOOLS THAT IMPROVE ASPECTS OF DOSING IN THE SPACIAL AND TEMPORAL DOMAIN AND INCREASING THE PRECISION AND STUDIES TO ANSWER UNANSWERED QUESTIONS ABOUT MECHANISMS AND DOSE-RESPONSE RELATIONSHIPS TO BE BETTER INFORMED WHEN WE APPLY THE TOOLS TO TRY TO TREAT CONDITIONS. WE ALSO HAVE UNMET RESEARCH QUESTIONS ABOUT HOW THESE THINGS WORK AT A CELLULAR AND SUB CELLULAR LEVEL. THIS HAS BEEN AN AREA OF ACTIVE DISCUSSION AS WELL. I'M SHOWING YOU THE TITLES OF FUNDING PROJECTS AND THEY DISTRIBUTED IN THE MATERIALS. YOU CAN SEE THESE ARE TARGETED AT REACHING BRAIN TARGETS AND HOW TO UNDERSTAND DOSE RELATIONSHIPS. IN ADDITION TO TMS, THEY'RE LOOK AT TRANS CRANIAL DIRECT STIMULATION AND ALTERNATING CURRENT STIMULATION TO UNDERSTAND HOW TO RATIONALLY OPTIMIZE IT TO NEUROOSCILLATIONS OR EFFECT THE FUNCTIONS FOR COMPLEX DISORDERS AND PROVIDE TOOLBOXES OTHER RESEARCHERS CAN USE TO OPTIMIZE THE PARADIGM AND ANSWER THEIR SCIENTIFIC QUESTION AND ADDRESS THEIR CLINICAL CONDITIONS. THERE'S OTHER WAYS OF APPLYING ENERGY TO THE BRAIN. THERE'S ACOUSTIC STIMULATION. IT'S BEEN SHOWN IN STUDIES TO NOT ONLY ADD HIGHER DOSES CAN OPEN UP THE BROOD BRAIN BARRIER TO TARGETED REGIONS BUT AT LOWER INTENSITIES IT COULD BE A NEUROMODULATION AND IF YOU WERE ABLE TO FOCUS ULTRA SOUND DEEP IN BRAIN AREAS YOU MAY BE ABLE TO NON IN -- NONINVASIVE AND YOU CAN EFFECT CIRCUIT FUNCTION AS WELL. SO WHAT'S NEXT IN THE FIELD OF NONINVASIVE NEUROMODULATION? WE CAN ANTICIPATE INCREASING SUPPLIES OF CLINICS OFFERING THESE ON LABEL AND OFF LABEL AND SOME ARE FOR MEDICAL PURPOSE AND OTHERS ARE FOR LIFESTYLE ENHANCEMENT. THERE'S A DO-IT-YOURSELF COMMUNITY OF PEOPLE BUILDING THESE DEVICES FOR THEIR OWN PERSONAL USE. WE EXPECT IN THE FUTURE THERE'LL BE INCREASING DEMAND ADDS -- AS PUBLIC AWARENESS GROWS AND FAMILIES SEEK CARE FOR CLINICAL CONDITIONS NOT RESPONDING TO AVAILABLE TREATMENTS THERE'S INCREASING DEMAND FROM PATIENTS AND FAMILIES AND COMMUNITY TO TREAT CONDITIONS AND INCREASING DEMAND FROM CONSUMERS SEEKING WAYS THESE TOOLS COULD DELIVER NEUROENHANCEMENT OR COGNITIVE ABILITIES. THERE'S ALSO INCREASING NEED. NEEDS IN THE SPACE OF PROFESSIONAL GUIDELINES TO INFORM MEDICAL PRACTICE IN PARTICULAR WITH RESPECT TO FDA LABELLED CONDITIONS AND OFF-LABEL PRACTICE AND OVER THE COUNTER AND CONSUMER PRODUCTS TO EDUCATE THE PUBLIC. WHAT THEY CAN EXPECT THE PRODUCTS TO DO FOR THEM AND KNOWLEDGE ON WHAT MIGHT BE THE LONGER TERM RISKS AND SAFETY OF THE USE OF THE PRODUCT. AND NEED FOR OPTIMAL METHODS TO ENSURE THE SAFE AND EFFECTIVE USE OF THE INTERVENTIONS. I'D LIKE TO END THERE AND AM HAPPY TO ANSWER QUESTIONS. THE VERY MUCH. THANK YOU VERY MUCH. NEUROMODULATION >> THERE ARE SOME STUDIES UNDERWAY EXAMINING THE USE OF THE PRODUCTS ON THE PERFORMANCE OF ELITE ATHLETES AND COGNITIVE PERFORMANCE. I WOULD SAY WE HAVE INSUFFICIENT KNOWLEDGE IN WELL CONTROLLED RANDOMIZED CONTROLLED TRIALS. >> I WAS WONDERING ABOUT USING INFORMATION WE GET FROM INVASIVE DEVICES IN TERMS OF TARGETING AND FOCALITY OF TREATMENT AND APPLYING THAT TO NONINVASIVE. IS THERE AN EFFORT TO MERGE THESE TWO AREAS? >> SO IN PRINCIPLE THE CIRCUIT IS THE SAME WHETHER WE'RE ACCESSING IT NONINVASIVELY OR INVASIVELY IT CAN HELP FURTHER THE KNOWLEDGE OF THE BASIC PATHOLOGY OF THE DISORDERS. I THINK IN TERMS OF WHAT IMPACT IT HAS ON THE DISTRIBUTED NETWORK COULD HELP IDENTIFY TARGETS THAT MIGHT BE ACCESSED NONINVASIVELY OR VICE VERSA. I DO THINK THE FIELDS HAVE A LOT TO TEACH EACH OTHER ABOUT THE BRAIN BASED OF THE CONDITIONS THAT CAN LEAD TO OPTIMIZING INVASIVE AND INVASIVE APPROACHES TO TUNE THE CIRCUITS. >> WHAT IS KNOWN ABOUT THE POTENTIAL OF THE TECHNOLOGIES p>> SO THIS IS AN AREA THAT IS BEING ACTIVELY STUDIED IN PARTICULAR WITH TRANS CRANIAL MAGNETIC STIMULATION. THERE'S BEEN STUDIES ON EXAMINING THE EFFECTIVENESS SUCH AS CIGARETTE SMOKING AND COCAINE AND OTHER DRUGS OF ABUSE. THERE'S ONE WAY NEUROMODULATION MAY BE USEFUL THERE'S AND DEF A IT CAN PROVIDE RELIEF FOR THOSE ALREADY ADDICTED TO SUBSTANCES IS A PROMISING AREA OF RESEARCH. IT'S NOT CURRENTLY FDA APPROVED FOR ADDICTION BUT RESEARCH IS UNDERWAY ADDRESSING EXACTLY THAT QUESTION. >> THANK YOU FOR A WONDERFUL TALK. I'M PART OF SEVERAL DSMBs IN NONINVASIVE FOR THE TECHNOLOGIES PARTICULARLY THE SHAM EXPERIENCES WILL BE VERY HELPFUL AS WE THINK ABOUT WHAT THE BEST SHAM IS. WHAT EFFORTS ARE BEING MADE TO CREATE REGISTRIES OF LONG-TERM EFFECTS OF THESE FOR BALANCE ISSUES THAT MAY IN THE END COME UP SO WE CAN TRACK THEM SO WE KNOW LONG TERM? >> SO YOU RAISE AN INTERESTING POINT ABOUT THE ROLE FOR REGISTRIES FOR THE LONG TERM USE OF THE TECHNOLOGIES. I'M NOT AWARE OF NATIONAL OR INTERNATIONAL REGISTRIES BUT I WILL POINT OUT LEADING UP TO THE STUDY THERE WERE LONG-TERM FOLLOW-UP STUDIES THAT LOOKED AT SENSITIVE NEUROCOGNITIVE MEASURES AND FOUND NO EVIDENCE OF NEUROCOGNITIVE DECLINE BUT WHEN YOU LOOK AT THE EFFECTS ON NEUROLOGICAL FUNCTION MOST STUDIES THAT HAVE BEEN LONG-TERM FOLLOW-UP, THAT MEANS MONTSIX MONTHS AND THE LONG-TERM FOLLOW-UPS HAVE BEEN ONE TO TWO YEARS OR LONGER LEEK FOUR YEARS. I THINK YOU RAISE A GOOD POINT. THERE'S A NEED. I'M NOT AWARE OF REGISTRIES FOR THE LIFESTYLE PRODUCTS WHAT LONG-TERM USES MAY PROVIDE AS WELL. I WILL POINT OUT IN TERMS OF CLINICAL PRACTICE, THERE IS A WAY TO REPORT ADVERSE OUTCOMES TO THE FDA. FOR DEVICES SPECIFICALLY IF CLINICIANS ARE USING THESE DEVICES AND HAVE CASES THAT HAVE ADVERSE EVENTS THESE ARE REPORTED ON THE FDA WEBSITE WHICH IS IMPORTANT TO INFORMING PRACTICE. >> THERE'S VARIANCE ON WHO YOU PUT IT IN AND THINK ABOUT IT PROBABLY AND SORRY TO BE PRESCRIPTIVE HERE BUT A CIRCUIT MAY BE APPROACHABLE IN DIFFERENT WAYS OUTSIDE, INSIDE, DIFFERENT NODES BUT NOT ALL ROADS ARE OPEN. AND WE WON'T KNOW WHERE TO INTERVENE AND WILL HAVE A LOOK AT SMALL GROUPS AND CRASHES WITH A LARGE GROUP BECAUSE WE DON'T UNDERSTAND THE VARIANCE OF THE DISEASE WE'RE STARTING WITH AND WITH STEM IT MAY BE HARMFUL IN DIFFERENT PLACES LONG TERM. ONE SIZE DOESN'T FIT ALL FOR ANY OF THE ABOVE. >> I THINK YOU'RE MAKING A VERY IMPORTANT POINT IN SOME OF YOUR WORK HAS ILLUSTRATED THE IMPORTANT ROLE OF INDIVIDUAL DIFFERENCES IN THE CONNECTIVITY WHERE IT STIMULATION TARGET IS AND THE SYNAPTIC ACTION MAY BE THE DIFFERENCE IN RESPONSE AND NOT. THESE ARE NOT JUST WAYS TO LOOK AT IN WHOM IT IS CONDUCTED. >> I WANT TO RETURN TO THE DISCUSSION OF ADDITION. I WONDER IF THERE'S HISTORY OF OVERUSING THESE AND BECOMING ADDICTED TO THE USE OF THESE. >> THAT'S A VERY IMPORTANT QUESTION. AND I HAVE NOT SEEN ADDICTIVE POTENTIAL AND WHAT YOU'RE TALKING ABOUT IS MISUSE. WE SEE WHEN WE STOP THE USE THERE'S NO PROOF OF WITHDRAWAL. THE INTERVENTION IS OBSERVED AND THEY DON'T TAKE THE DEVICE HOME WITH THEM. THE OPPORTUNITY FOR MISUSE COMES INTO PLAY WHEN YOU TALK ABOUT THE PORTABLE TECHNOLOGIES THAT PEOPLE COULD ACCESS AND USE AT HOME. AND THAT'S WHERE I THINK IT WOULD BE USEFUL TO COMMUNITY TO THE PUBLIC THE SAFETY EFFECTS AND RISKS OF LONG-TERM USE. THAT PRACTICE MAY BE OCCURRING TODAY. >> I DID THINK WE HAVE A RESPONSIBILITY TO THE PUBLIC TO PROVIDE INFORMATION ABOUT THE SAFETY AND RISKS OF THE PRACTICE IN THIS AREA AND WHEN IT'S NOT AN APPROPRIATE USE IT MAY PREVENT THE PERSON FROM SEEKING THIS TO BE A MEDICAL PRODUCT. >> I STUDIED THE DO-IT-YOURSELF COMMUNITY. WHAT I FOUND REGARDING HOW THEY USE THE TECHNOLOGY IS THAT THEY GENERALLY ADHERE TO THE USE IN SCIENTIFIC STUD AND THE DURATION OF 20 MINUTES GIVE OR TAKE. WHERE THEY DEPART IS IN THE LONG-TERM USE OF TDCS. THEY SELF-STIMULATE MORE FREQUENTLY THAN THE TYPICAL NUMBER OF SESSIONS IN SCIENTIFIC STUDIES. THERE'S A SMALL GROUP OF SUPER USERS THAT HAVE USED IT A HUNDRED OR MORE TIMES ON THEMSELVES AND WITH THE ADVERTISING AND REGULATION ON THE DIRECT TO CONSUMER PRODUCT IT'S TRICKY. SOME MARKET THEMSELVES FOR COGNITIVE ENHANCEMENT AND SOME MAKE MEDICAL CLAIMS AND TOW THE LINE. IT'S A TRICKY QUESTION. >> THANK YOU FOR THAT COMMENT. YOU'RE WORK TO HELP INFORM WHAT IS CURRENTLY BEING DONE IN THE DO-IT-YOURSELF COMMUNITY IS IMPORTANT TO UNDERSTAND. I WOULD ASK YOU WHETHER YOU HAVE DATA ON THE AGE. MOST THE WORK IS IN ADULTS. WHEN YOU THINK OF THE PUBLIC USE OF THE LIFESTYLE PRODUCTS, CHILDREN, ADD -- ADOLESCENTS WE DON'T HAVE SUFFICIENT EVIDENCE ON THE EFFECT ON THE DEVELOPING BRAIN. THANK YOU VERY MUCH. >> NOW WE'LL HEAR ABOUT THE INVASIVE SIDE WITH DR. SAMER SHETH FROM COLUMBIA UNIVERSITY. >> CONGRATULATIONS ON THE RECENT EXCITING NEWS. GLAD TO BE HERE. THIS IS A VERY NECESSARY DISCUSSION TO HAVE. HAPPY TO TELL YOU GUYS A LITTLE BIT ABOUT THE INVASIVE SIDE OF THINGS AND WHERE WE ARE NOW AND HOPEFULLY SET THE STAGE FOR THE REST OF DISCUSSIONS WHICH ARE TIMELY. I'LL TALK ABOUT THE CLINICAL OPPORTUNITIES. I KNOW WE HAVE A DIVERSE CROWD SO I'LL TALK ABOUT THE TYPES OF PROCEDURES AND DEVICES WE USE THESE DAYS IN REGULAR CLINICAL PRACTICE BECAUSE THEY FORM THE BASIS OF THE RESEARCH AND PROVIDE THE OPPORTUNITIES THAT WE TAKE ADVANTAGE OF FOR RESEARCH. THEN CATEGORIZE THEM. THEM SOMEWHAT ARBITRARILY BUT GO TO LOW RISK AND ZERO RISK ACTIVITIES AND THOSE WITH NO BENEFIT AND IT'S PROBABLY A DIFFERENT CALCULATION. GETTING INTO IT, DEEP BRAIN STIMULATION HOLLY MENTIONED BEFORE, WHAT IS IT. IT'S BASICALLY A COMBINATION OF THE LEAD TO THE BRAIN AND THE EXTENSION WIRE TO A BATTERY PACK THAT SITS UNDER THE SKIN. YOU TALK TO PATIENTS THAT IT'S LIKE A PACE MAKER FOR THE BRAIN AND ENACTS WHATEVER EFFECT WE'RE HOPING FOR IT TO ENACT. IT'S PROGRAMMABLE IN ADJUSTABLE IN OUTPUT. THE FDA ARE TREMOR, PARKINSON'S DISEASE AND DYSTONIA AND OCD EVERYTHING ELSE IS OFF-LABEL AND INVESTIGATIONAL. WE USE WE LOOK AT THE ELECTRODE TO GET IT IN THE BRAIN. HISTORICALLY AND STILL NOW OFTEN WE USE MICROELECTRORECORDING BEFORE WE PUT THE LEAD IN WE ADVANCE THE ELECTRODE BY MAPPING THE AREA TO UNDERSTAND WHAT CELLS ARE PRESENT AND LOOK FOR CELLS THAT TELL US WE'RE IN THE RIGHT STRUCTURE. BOTH THE PRESENCE OF THE LEAD AND THE MICROELECTRODE PROVIDE RESEARCH IDEAS. OFTEN TIMES PATIENTS ARE AWAKE AND THE PATIENT WILL BE AWAKE ESPECIALLY IN THE MIDDLE PART OF THE PROCEDURE THIS PATIENT IS FOR TREMOR ONCE HAVE YOU THE LEAD IN YOU TEMPORARILY TURN IT ON. ONE THE WAKE PATIENT AN OPPORTUNITY STUDY THE BRAIN. SOME OF THE NEWER DEVICES HAVE OUTPUT STIMULATION AND PROVIDE RECORDING FROM THE BRAIN. THIS IS A PICTURE OF AN INVESTIGATIONAL DEVICE. THE PCS, THE "S" BEING SENSING. THEY SIT UNDER THE SKIN AND ARE ABLE TO RECORD AND PROVIDE THE OPPORTUNITY FOR KNOWING WHAT THE BRAIN IS DOING BASELINE IN OR IN RESPONSE TO WHAT YOU'RE DOING AND TO FASHION A CLOSED LOOP SYSTEM AND UNDERSTAND THE STATE OF THE SYSTEM NOW AND THEN WHAT DO I NEED TO DO TO TWEAK IT OR PERTURB IT IN THE DIRECTION I WANT TO. OTHER OPPORTUNITY BESIDES DEEP BRAIN STIMULATION IS EPILEPSY. A THIRD OF PATIENTS ARE MEDICAL MEDICALLY REFACTORY. AND THIS IS TO TRY PROVIDE INFORMATION TO PROVIDE A SURGICAL OPERATION WHERE WE PLACE ELECTRODES TO IDENTIFY WHERE THE SEIZURES ARE COMING FROM. THERE'S A COUPLE WAYS. ONE IS STEREO -- SO A PLAN IS MADE WHERE THE THEY'LL BE PLACE STER STEREOTACTICALLY AND THEN THE PATINT IS MONITORED FOR DAYS OR WEEKS UNTIL WE SEE WHERE THE SEIZURES ARE COMING FROM. ELECTRODES IN THE BRAIN, OPPORTUNITY FOR RESEARCH. AND THERE'S ADVANTAGES AND ANOTHER WAY OF GETTING ELECTRODES IN THERE. PATIENTS ARE MONITORED PROVIDING AN OPPORTUNITY TO STUDY THE BRAIN. AND ANOTHER IS RESPONSIVE NEUROSTIMULATION. THIS IS EVEN MORE OF A PACE MAKER THAN DBS BECAUSE IT'S THE FIRST AND ONLY CLOSED-LOOP SYSTEM. THIS IS PLACED FLUSH WITH THE REST OF THE SCHOOL AND THERE'S A COMBINATION OF ELECTRODES PLACED IN THE BRAIN IN THE DEF AND IT WILL SENT A DOES -- IT'S A WAY TO DETECT AND ABORT A SEIZURE ONSET. SO THE FRAMEWORK FOR THE STATE OF THE SCIENCE NOW IS PUT INTO CONSIDERING OF RISK VERSUS BENEFIT TO THE PATIENT. THAT'S IMPORTANT IN IDENTIFYING THE TYPES OF ACTIVITY. I'LL BRIEFLY TALK ABOUT ZERO RISK. WHAT I CALL ZERO RISK ACTIVITIES. THEN GOING TO THE TWO THAT HAVE A HIGHER THRESHOLD FOR RISK IN THE MANIPULATION OR DEVICE IS BEING USED AND SEPARATE THEM WHETHER THERE'S INTENT FOR THERAPEUTIC BEEN -- DEN -- BENEFIT OR NOT. IN THESE CASES WE HAVE DATA THAT COMES ALONG THE WAY IN ANY CLINICAL PROCEDURE FOR DOING MICRORECORD DURING THE DBS CASE OR 24/7 RECORDINGS IN AN EPILEPTIC PATIENT. THAT DATA IS SOMEWHERE AND CAN BE STUDIED FOR WHATEVER QUESTIONS. THIS IS TYPICALLY DONE POST HOC, OFFLINE. THE PATIENT WILL MAYBE SIGN CONSENT, YOU CAN USE MY DATA BUT A PATIENT DOESN'T HAVE TO DO ANYTHING. NOTHING IS DONE BEYOND THE CLINICAL PROCEDURE. HERE'S EXAMPLES OF WHAT THOSE THINGS WOULD BE. TIS LOOKS AT SLEEP OR RNS DEVICE THAT CAN RECORD BRAIN ACTIVITY IN A MORE NATURALISTIC SURROUNDING BECAUSE THE PATIENT TAKES IT HOME AND HAS IT MONTHS AND YEARS. THAT'S OFFLINE DATA. NOW GETTING INTO THE MORE INTERESTING STUFF THAT GETS IN THE ETHICAL DILEMMAS WE'LL BE FACING. FIRST THE CATEGORY OF TYPES OF ACTIVITIES WHERE THERE'S REALLY NO OBVIOUS INTENT FOR THERAPEUTIC BENEFIT REALLY JUST TRYING TO UNDERSTAND HOW THE BRAIN WORKS AND IMPROVE THE SCIENCE. ARBITRARILY I CLASSIFIED THESE AS THE RISK THAT WE ARE ASKING THE PATIENT TO THINK ABOUT ACCEPTING IS RELATED TO THE MANIPULATION BEING ASKED OF THE PATIENT OR RELATED TO A PARTICULAR DEVICE THAT WILL BE USED. LET'S LOOK AT THESE. MANIPULATION RELATED RISK. IT'S PROCEDURAL MANIPULATION THAT INVOLVES THE PATIENT THAT IS NOT REQUIRED FOR THE CLINICAL PROCEDURE. IT'S A RESEARCH MANIPULATION. ASKING THE PATIENT TO PERFORM A BEHAVIORAL TASK. PLAY THIS GAME BECAUSE WE'RE STUDYING THIS NEUROCOGNITIVE FUNCTION OR THINGS WE DO LIKE STIMULATION OF THE DWELLING ELECTRODES IN THE BRAIN. FOR THE PURPOSE OF DISTINCTION I'LL SAY THESE ARE ONES WE CAN THINK ABOUT DOING WITHOUT ANY ADDITIONAL INVESTIGATIONAL DEVICES AND ADDING ADDITIONAL MANIPULATION. WHAT ARE WE DOING IN TERMS OF THE EXAMPLE? FOR THE SUB DIVIDED MANIPULATION RISK WHAT DO THEY LOOK LIKE. YOU CAN HAVE AN INTEROPERABLE BEHAVIORAL TASK AND THIS IS A DBS CASE AND THE MICRO DIVE AND BUREAU HERE AND THE PATIENT'S AWAKE AS I MENTIONED DURING THE PROCEDURES FOR PARKINSON'S FOR EXAMPLE TO SEE IF THE TREMOR IS IMPROVING. AND IF YOU DON'T MIND WE'LL PAUSE FOR A FEW MINUTES AND ASK YOU TO PERFORM THIS GAME WHILE WE RECORD FROM THE BRAIN AND HERE'S WHY WE'RE DOING THIS. THIS IS WHAT THAT WOULD LOOK LIKE. ANOTHER WAY WE HAVE OF DOING THIS WITH JUST A BEHAVIORAL TASK IS TAKE A PATIENT WITH EPILEPSY WITH THEM IMPLANTED. NOW THEY'RE IN THE HOSPITAL WITH ELECTRODES ATTACHED TO A MONITORING DEVICE AND BRING IN A COMPUTER SYSTEM AND SAY PLEASE PLAY THIS GAME. WE'RE RECORDING YOUR BRAIN ACTIVITY SO WHILE YOU'RE WAITING TO HAVE SEIZURES YOU CAN HELP US OUT. WHAT ARE THE RISKS? MAYBE DISCOMFORT. MAYBE SOME ANXIETY WHEN YOU'RE IN THE O.R. TRYING TO FOCUS ON THE GAME. ADDITIONAL PROCEDURE TIME. IN THIS CASE. WE COULD BE SETTING UP THE NEXT STEP OF THE SURGERY BUT THERE MAYBE ADDITIONAL TIME WHERE THE PATIENT IS PERFORMING THIS GAME OR BEHAVIORAL TASK. WHERE ARE WE AND AS WE BEEN GOING ON. WE TRIED TO LOOK BACK AT THE ORIGINAL STUFF. THIS IS WORK FROM 2004. SO THIS HAS BEEN GOING ON SINCE THE EARLY 2000s WHICH DBS HAS ONLY BEEN APPROVEDANCE APPROVED FROM '97. WE CAN LOOK AT THE PHYSIOLOGY OF THE OSCILLATIONS OR FIRING OF THE NEURONS ASSOCIATE WITH THE MOVEMENT DISORDERS. THERE'S EXAMPLES OF LOOKING AT THE OSCILLATIONS INVOLVED IN PARKINSON'S DISEASE AND TRYING TO UNDERSTAND WHAT THEY'RE TELLING US ABOUT THE DISORDER AND HOW THEY MAY BE CHANGING WITH STIMULATION. THE MGH GROUP ON TOP AND STANFORD GROUP OVER HERE. WE CAN ALSO LOOK AT OTHER COGNITIVE PROCESS AND PHYSIOLOGY. HERE'S RECORDING IN THE CORTEX AND PREFRONTAL CORTEX. WE'RE INTERVENING HERE AND SEEING PROCEDURES FOR OCD AND DEPRESSION. IN THIS INDICATION REGULAR OLD PARKINSON'S OR TREMOR CASE WHERE ALONG THE TRAJECTORY AT THE TOP OF THE CORTEX OR IN THIS CASE IN THE TARGET STRUCTURE OF THE CORTEX WE'LL BE HERE ANYWAY AND WE'LL PAUSE AND TRY TO LEARN SOMETHING ABOUT WHAT THE NEURONS ARE DOING. HERE'S SOME EXAMPLES FROM EPILEPSY MONITORING UNIT IN PATIENTS WHERE THERE'S A GRID IN LANGUAGE AREAS. WE CAN TRY TO UNDERSTAND THROUGH THE STUDY FROM COLUMBIA LOOKING AT HOW SPEECH CAN BE SELECTIVELY TRACKED AND TRYING TO PAY ATTENTION OVER ANOTHER IN A COCKTAIL PARTY WAY. INNUMERABLE ASPECTS EN HOW THE BRAIN FUNCTION IS WORKING. UPPING THE ANTE WE CAN INCLUDE IT SAME RISK AS BEFORE AND THEY CAN DO SOMETHING IN ADDITION TO SITTING AROUND AND WE ADD STIMULATION AND THERE'S AN A STUDY THAT LOOKED AT HOW IT CAN EFFECT MEMORY. COULD IT ENHANCE IT OR IMPAIR IT. THEY FOUND STIMULATION APPLIED AND THEY HAVE IMPAIRED MEMORY IN ADDITION TO A STUDY A COUPLE YEARS BEFORE FROM UCLA SHOWING STIMULATION CAN ENHANCE MEMORY. WE CAN USE THE OPPORTUNITY TO SEE HOW THE BRAIN IS CONNECTED. IF YOU STIMULATE THE AREA SUPPOSE HAVE YOU LEC ROAD TOS ALL OVER THE BRAIN YOU CAN SEE HOW OTHER AREAS RESPOND AND UNDERSTAND HOW FUNCTIONALLY THE REGIONS ARE CONNECTED AND UNDERSTAND THE NETWORKS UNDERLYING THESE. THE STUDY FROM LONG ISLAND DOING THIS. MOVING TO A DIFFERENT RISK CATEGORY. RATHER THAN JUST ASKING THE PATIENT TO DO SOMETHING OR APPLYI APPLYING STIMULATION THESE ARE DEVICE-RELATED RISKS. I'LL DEFINE FOR THE PURPOSE OF OUR DISCUSSION AS OUT -- UTILIZATION OF THE DEVICE AND PUTTING ELECTRODES AND YOU HAVE ADDITIONAL ELECTRODES WHERE YOU DON'T NEED THEM FOR A CLINICAL REASON. SOMEWHERE OR SOME ELECTRODE NOT REQUIRED CLINICALLY. OR YOU CAN USE AN INVEST -- INVESTIGATIONAL DEVICE. AND THERE'S ELECTRODES ALREADY THERE BUT HAVE ADDITIONAL FUNCTIONALITY TO RECORD MORE DATA THAN THEY WOULD OTHERWISE. SO WHAT'S THE STATE OF THE SCIENCE IN THIS STUFF. MINIMAL RISK. SO HERE'S A PICTURE OF A DBS CASE. YOU MAKE A SMALL OPENING IN THE SKIN, AN AND YOU CAN PUT IT OVER THE CORTICAL SURFACE. WHAT'S THE RISK? WELL, WE'LL PUT IT ALONG THE BRIDGING OF THE BRAIN AND IF THERE'S TEARS THAT'S A BAD THING BUT THAT'S FAIRLY UNCOMMON IN EXPERIENCED HANDS. IT'S UNLIKELY IT WILL HAPPEN. HERE'S THE UCSF GROUP. THE 200 CASES THEY DID. THE DBS ELECTRODE YOU CAN'T SEE BUT HERE'S THE SIX CONTACT STRIP ELECTRODE IN THIS CASE OVER THE MOT MOTORCORTEX IN RELATION TO STUDYING PARKINSON'S AND THEY'RE TRYING TO UNDERSTAND THE RELATIONSHIP BETWEEN DEEP NUKE -- NUCLEI AND THERE'S A DEVICE THAT CANNOT ONLY STIMULATE AND RECORD AND TAKE ELECTRODES IN COMBINATION WITH CORTICAL STRIP ELECTRODES AND IMPLANTING THEM PERMANENTLY WITH A DEVICE THAT CAN RECORD AND STIMULATE. AND THERE'S A GROUP WHERE THEY'RE TRYING TO TREAT A COMBINATION OF DBS HERE IN THE THALAMUS AND CAN WE ONLY APPLY IT WHERE IT'S NEEDED. A PATIENT WITH ESSENTIALLY DOESN'T NEED TO BE ON BUT WHEN THEY'RE TRYING TO GRAB THEIR CUP OF COFFEE THAT'S WHEN MAYBE THE STIMULATION CAN BE TURNED ON AND WE CAN CONSERVE BATTERY LIFE AND ETCETERA. AND HERE'S THERE'S TOURETTE AND IT'S APPROVED FOR EPILEPSY AND THEY'RE TRYING TO DO THE CLOSED LOOP FASHION. TOURETTE THE SYMPTOMS ARE EPISODIC. THE TICKS MAY BE FREQUENT BUT THEY'RE EPISODIC EVENTS. CAN THEY IDENTIFY A PHYSIOLOGICAL SIGNATURE OF WHEN THE PATIENT IS GOING TO TICK AND TRY TO SUPPRESS IT AT THAT MOMENT AGAIN WEN THEY'RE SLEEPING OR WHEN THEY'RE NOT TICKING THEY MAY NOT NEED IT ON IN A CONTINUOUS OPEN-LOOP FACTION. YOU TAKE A CLINICALLY INDICATED ELECTRODE AND ADD FUNCTIONALITY. HERE'S AN ELECTRODE AND THESE ARE CLINICAL CONTACTS TO DETECT SEIZURES BUT IT'S GOT A SPRAY OF MICROWIRES THAT COME OUT THE TRIP AND TYPICALLY TRIMMED TO MILE MILLIMETERS AND THIS PROVIDES THE ACCESS TO SINGLE-UNIT DATA. HERE'S WORK FROM THE CEDAR SINAI GROUP IN L.A. WHERE EPILEPSY PATIENTS HAVE THE SPRAY OF MICRO WIRES OF THE AMYGDALA AND HAD SCANNING PATTERNS AND FINDING NEURONS THAT RESPONDED TO WHEN THE PATIENT LOOKED AT FACE AND EYES VERSUS MOUTH. AND HERE'S STUFF IF THE CAL TECH GROUP WHERE NEURONS IN THE MEDIAL TEMPORAL LOBE RESPOND SPECIFICALLY TO CERTAIN FAMOUS PEOPLE. THIS IS THE JENNIFER ANISTON NEURON. THIS ONE NEURON AND THEY FOUND HALLE BERRY NEURONS AND OTHERS. AND THERE'S REDUCED RISK BECAUSE THE ELECTRODES ARE THERE ANYWAY. THIS IS A STUDY FROM NYU THAT CAME OUT ON THE NEUROGRID. THIS IS A NEW GENERATION OF REGARDING ARRAY ARE ULTRA THIN A FEW MICRONS THIN. A BUNCH EMBEDDED WITH SILICON AND GOLD AND PLATINUM AND STUFF CONNECT TO THE APPROPRIATE HARDWARE. THESE ARRAYS -- THIS IS THE ARRAY. IT'S LIKE A PIECE OF CELLOPHANE AND NON-PENETRATING. PROBABLY LITTLE RISK AND CRANIOTOMY FOR A PATIENT UNDER DOING -- NO, I THINK THEY PUT THIS ARRAY ON THE SURFACE OF THE BRAIN AND RECORDED SOME POTENTIAL TO IDENTIFY A SINGLE NEURON OR MULTIUNIT ACTIVITY. THIS IS THE GROUP AT UNC. ULTRA THIN ARRAYS LAID ON THE SURFACE OF THE BRAIN WHERE THE RISK IS VERY LITTLE AS LONG AS THEY'RE MADE PROPERLY. WE CAN INCREASE THE ELECTRODES ARE PENETRATING THE SURFACE OF THE BRAIN. THEY'RE THERE ONLY FOR RESEARCH PURPOSES. THIS IS GETTING INTERESTIG NOW. THIS IS A STUDY FROM CASE WESTERN WHERE THEY WANTED TO UNDERSTAND THE POSSIBILITY OF STIMULATING THE FORNIX AND THEY HAD MULTIPLE ELECTRODES PLACED FOR CLINICAL PURPOSE. THEY GOT APPROVAL FOR AN ELECTRODE IN TARGETING THE FORNIX AND IT'S NOT NEEDED FOR THE CLINICAL AND ONE MORE SHAFT GOING TO THE BRAIN FOR RESEARCH PURPOSE. AND THIS IS WHERE IT'S A 4x4 MILLIMETERISH TIME THAT CAN BE STAMPED INTO THE CORTEX. LOTS OF ANIMAL WORK BUT IT'S ALSO BEEN DONE IN HUMANS. THIS SAY STUDY FROM COLUMBIA AND HERE AT THE NIH. WHERE THESE ARRAYS ARE BEING IMPLANTED AGAIN IN PATIENTS WITH EPILEPSY. YOU HAVE A CRANIOTOMY AND HAVE ELECTRODES THERE FOR CLINICAL REASONS AND THEN YOU ADD THE ARRAY. THIS IS A RESEARCH ARRAY. AND NOW WE CAN RECORD FROM SINGLE NEURONS AND UNDERSTAND THE PHYSIOLOGY OF THAT PART OF THE BRAIN WITH GREAT DETAIL AND WHERE CAN WE PUT THESE IN? THERE ARE GROUPS AROUND THE COUNTRY, OUR APPROVAL SAYS WE CAN PUT THEM INTO AREAS AND YOU PUT IN IT AND CLOSE IT OUT AND WAIT FOR THE PERSON TO HAVE A SEIZURE AND YOU SEE WHERE THEY'RE COMING FROM AND NOW YOU KNOW WHERE THE SEIZURES ARE AND YOU CAN DISSECT THAT PART OF THE BRAIN WHERE THE SEIZURES ARE COMING FROM. YOU HAVE AN IDEA THIS IS LIKELY TO BE IN THE DIRECTION YOU MAY HAVE AN APPROVAL TO SAY OKAY WE'RE GOING TO PUT THIS IN AN AREA WE KNOW WILL COME OUT. IF THERE'S A LITTLE BIT OF DAMAGE, NO BIG DEAL. SOME PLACES ARE ALSO GOING FURTHER. AND THERE'S AREAS THAT WILL NOT NECESSARILY COME OUT. THE ARGUMENT BEING THEY'RE SMALL AND WE STUDIED THE DAMAGE THEY CAUSED AND IT'S MINIMAL. WE LOOK AT THE PATIENTS. LET'S PUT IT HERE BECAUSE WE ARE INTERESTED IN THIS AREA FROM A RESEARCH PERSPECTIVE. I MAY NOT COME OUT. IT WILL BE SLIGHTLY DAMAGED. AND THE LAST CATEGORY HERE THOSE ARE AREAS WHERE WE LEARN ABOUT THE BRAIN. NOW WHAT IF WE'RE TRYING TO HELP THE PATIENT. NEW INDICATIONS FOR EXISTING OR APPROVED INVASIVE DEVICES. OR NON CLINICAL DEVICES IN THIS FASHION. THERE'S DBS AND 4X. LIKE HOLLY'S SLIDE. THERE WAS WORK IN THE EMERY GROUP WITH DBS FOR DEPRESSION. DBS FOR ALCOHOL ADDICTION AND FOR PTSD FROM UCLA. HERE'S DBS FOR AUTISM AND SELF-INJURIOUS BEHAVIOR. THIS IS APPROVED FOR PARKINSON'S TREMOR AND WE'LL STUDY ANOTHER PART OF THE BRAIN BECAUSE WE THINK THERE'S A REASON TO DO SO. WE GOT APPROVAL TO DO THAT AND TRY IT OUT. NEXT GENERATION OF STUFF. HERE'S A YEAR AGO BRAIN THEIR TIF INITIATIVE GRANTS AND THEY'RE USING A DEVICE THAT CAN STIMULATE AND RECORD AND MAYBE COUPLE IT WITH MAYBE NOT A DBS EHECK ROAD TO. THEY'RE ELECTRODE AND THEY'RE DOING MORE OF THE FRONT OF THE BRAIN. THEY WANT TO SEE THE RELATIONSHIP BETWEEN THE NUCLEUS OR CAPSULE REGION. CAN WE DESIGN AN ADAPTIVE OR CLOSED-LOOP WAY OF WHEN THE PATIENT WILL HAVE MORE OCD BEHAVIORS AND USE THAT TO HELP THE PROGRAMMING. HOW DO WE PROGRAM DBS FOR OCD? FOR PARKINSON'S WE CAN SEE THE TREMOR IMPROVE WITHIN MOMENTS OF TWEAKING THE PARAMETERS. WITH OCD NOT SO MUCH. YOU MAKE A CHANGE AND IT COULD BE DAYS OR WEEKS TO SEE THE CHANGE AND BUT IF YOU HAVE A BIOMARKER DEVICE TO RECORD WE CAN HAVE THEM WORK BETTER. LASTLY, THIS IS FROM LIKE A MONTH AGO, AND THIS IS DOING DBS FOR DEPRESSION AND USING A DEVICE THAT CAN RECORD AND SAY DO WE HAVE PHYSIOLOGICAL EVIDENCE WE'RE IN THE RIGHT SPOT? HERE'S ONE TO GET STARTED ON WHERE WE'LL USE THE DBS DEVICE WIN DIRECTIONAL TUNING CAPABILITY. IF WE STIMULATE THIS NETWORK VERSUS OTHERS AND WE'RE LOOKING TO PUT INTRACRANIAL ELECTRODES INTO THE USUAL SUSPECT PLAYERS IN DEPRESSION AND UNDERSTAND THE INDIVIDUAL NETWORK BETTER AND TARGET IT WITH DIRECTIONAL STIMULATION. A LITTLE BIT ON AND OTHER DEVICES TO RECORD FROM AND STIMULATE PATIENTS AND TRY TO IN THIS CASE OVERCOME TETRAPLEGIA THE BRAIN GATE PROJECT AND BROWN, STANFORD, CASE WESTERN WHERE THEY TAKE PATIENTS WITH TETRAPLEGIA AND IMPLANT IT INTO THE MOTOR CORTEX AND DECODE THE ACTIVITY AND DRIVE PROSTHETICS ANNETTE SET RA. FINAL THOUGHTS AND WE HAVE LOTS OF INTERESTING DISCUSSIONS THE REST OF THE DAY, THIS IS BY NO MEANS COMPREHENSIVE BUT A FEW THINGS I CAN THINK OF TO HOW LONG WE CAN DO THIS AND STILL DO THE RIGHT THING. HOW MUCH ADDITIONAL BRAIN PENETRATION IS OKAY? WHERE SHOULD BE PUTTING IT AND IS THIS OUT OF ALTRUISM, YES, BUT HOW'S IT FRAMED? IS IT FRAMED AS PURELY RESEARCH? YES, THAT'S WHAT THE IRB SAYS. IS THAT REALLY WHAT'S HAPPENING. SLIPPERY SLOPE. MAYBE PUTTING ONE ELECTRODE IS OKAY. HOW MANY ADDITIONAL ELECTRODES IS OKAY AND IN WHAT CIRCUMSTANCES. WHERE CAN WE BE PUTTING THEM. WE'RE DOING THESE THINGS SAFELY AND SO CLINICALLY WE CAN SAY, LOOK, WE CAN LIKELY DO THIS WITH A LOW CHANCE OF CAUSING ANY KIND OF DAMAGE BUT HOW MUCH OF THAT IS OKAY. FOR TRIALS WE'LL TALK ABOUT WHO PAYS THOR THESE THINGS, WHAT'S THE TRIAL AND THAT'S WHAT WE'LL GET INTO THE PANEL DISCUSSION. I'LL STOP THERE AND I LOOK FORWARD TO DISCUSSION. [APPLAUSE] . >> Question: SO A COMMENT AND QUESTION. IN TERMS OF THE COMMENT ONE THING WE OFTEN ENCOUNTER IN BIOETHICS AN THINGS BEING USED IN DIFFERENT WAYS AND A CAUTION ABOUT THE TERM MINIMAL RISK WHICH HAS ESTABLISHED MEANING WHICH IS RISK NOT BEYOND THOSE ORDINARILY ENCOUNTERED IN EVERYDAY LIFE. I CAUTION ABOUT THE USE OF MIN MINIMAL RISK FOR AN ELECTRODE WITH WIRES. IT SEEMS A BIT BEYOND. THAT'S A COMMENT. AS A QUESTION -- I THINK WE'RE TALKING IN RELATIVE TERMS ABOUT THESE KINDS OF PROCEDURES. I THINK IT'S IMPORTANT TO DISTINGUISH BETWEEN SURFACE AND DEPTH AND AS YOU SAID RECORDING AND TISSUE INTENDED FOR RECESSION VERSE YOU NOT INTENDED FOR RESECTION. I THINK IT'S IMPORTANT TO MAKE DISTINCTIONS FOR RISK OR SETTLE ON TERMINOLOGY THAT ALLOWS THE DISTINCTION. I'M A NEUROLOGIST AND WHEN HAVE YOU A PENETRATING ELECTRODE THAT DOESN'T REQUIRE A LOT OF CORTICAL EXPOSURE. THAT'S THE COMMENT THAT WENT LONGER THAN I INTENNED. -- INTENDED. WE HAVE BEEN WORRIED ABOUT THESE ARE PATIENTS UNDERGOING PROCEDUR PROCEDURES REFACTORY AND AS A CLINICIAN HOW YOU OBTAIN CONSENT AND HOW YOU MITIGATE THERAPEUTIC MISCONCEPTIONS. PATIENTS ARE UNDERGOING A LOT OF PROCEDURES AND TESTING. ONE EXAMPLE IS SOMEONE WHO'S GETTING ECOG FOR THERAPY AND MAPPING OUT THE RECESSION AND AN HOUR LATER SOMEONE ELSE MAY COME TO DO LANGUAGE MAPPING TASK TO LEARN MORE ABOUT THE LANGUAGE SYSTEM. HOW DO YOU THINK ABOUT CONSENT, WHO OBTAINS CONSENT AND HOW TO HELP PATIENTS DISTINGUISH BETWEEN PROCEDURES THAT ARE DONE FOR GUIDING THEY'RE TREATMENT AND FOR ADVANCING SCIENTIFIC KNOWLEDGE. >> I THINK THE WHOLE FIRST PANEL IS ON THIS BUT MY BRIEF RESPONSE TO THE QUESTION, WHEN I WAS AT MASS GENERAL I THINK IN THE IRB IT SAID THE CLINICIAN RESPONSIBLE FOR THE PATIENT SHALL NOT OBTAIN CONSENT. OUR IRB DOESN'T SAY THAT BUT THE -- 99% OF THE TIME I'LL TELL THE PATIENT IN A DISCUSSION SEPARATE FROM THE CLINICAL DISCUSSION SAY LOOK, WE TALKED ABOUT THE CLINICAL PROCEDURE AND YOU'RE ON BOARD. THERE'S RESEARCH WE'RE DOING THAT SURROUNDS THIS AND WOULD OCCUR AT SOME POINT AND ARE YOU OKAY HEARING ABOUT THIS. YOU CAN BE TOLD ABOUT IT AND DO IT OR NOT DO IT. THE BENEFIT IS NOT TO YOU, IT'S TO WHATEVER. BUT HAVE THE DISCUSSION IF YOU'RE INTERESTED. ARE YOU INTERESTED, YES OR NO. AND TRY NOT TO BE THE ONE THAT'S THERE HAVING THEM SIGN THE PAPER. THE VAST MAJORITY OF THE TIME WE CAN DO THAT. THE COMMENT I THINK IS A GOOD ONE THERE'S THE NEUROETHICS TERMINOLOGY AND THE NON-SIGNIFICANT RISK DEVICE WHICH IS NON-PENETRATING, NOT IMPLANTED OR DOESN'T CAUSE HARM. SOMETHING LIKE A THIN FILM ARRAYS. WE'RE DOING THAT BECAUSE IT'S AN NSR DEVICE BY THAT CLASSIFICATION. TERMINOLOGY IS IMPORTANT. >> >> Question: WITH THE LONGER TERM REASON WHAT CAN YOU SAY ABOUT THAT? >> THE ONES THAT ARE FDA APPROVED FOR THOSE THAT ARE EPILEPSY RECORDED THEY'RE FDA APPROVED. CERTAINLY SOMETIMES IT GOES LONGER. FOR STUFF THAT IS NOT USED CLINICALLY LIKE THESE THIN-FILM ARRAYS AND THEY'RE NOT BEING USED IN A PERMANENT WAY. THEY'RE BEING PUT ACUTELY ON AND TAKEN OFF WITHIN MINUTES. THE PEOPLE MAKING THEM ARE INTERESTED IN DOING THIS LONGER TERM. IT COULD BE GOOD SCIENTIFIC AND CLINICAL REASONS TO DO SO BUT OBVIOUSLY IT WILL HAVE TO PASS A HIGHER THRESHOLD OF SAFETY AND LONG-TERM DURABILITY. >> AND I WANTED TO FOLLOW UP ON THE RISK QUESTION BECAUSE HAVE A NEUROSURGEON'S POINT OF VIEW ONES MADE ARE IMPORTANT. I HOPE WE CAN HAVE A DISCUSSION IN HOW GOOD WE ARE ABOUT FOLLOWING THE NEUROBEHAVIORAL OUTCOME IN TERM OF RISK. BECAUSE THERE'S A LONG HISTORY THAT WE'RE NOT VERY GOOD AT MEASURING THOSE KINDS OF THINGS. IN SCHOOL WE THOUGHT ASL WAS A MOTOR DISEASE AND BASAL GANGLIA WAS MOTOR. SO ARE WE REALLY VERY GOOD AT DETECTING NEGATIVE OUTCOMES OF OUR INVASIVE PROCEDURES ESPECIAL ESPECIALLY IT'S CLINICAL. >> AND IT'S HARD ENOUGH TO GET PATIENTS WITH PARKINSON'S BACK FOR A FOLLOW-UP NEUROPSYCHOLOGICAL EXAMPLE AFTER THE DBS, WILL INSURANCE COVER IT. WE'RE BAD ENOUGH IN KNOWING THE MEDICAL PROCEDURES. THE INCREMENTAL PROCEDURES WITH 15DBS VERSUS ADDITIONAL IS WELL THE NOISE. >> Question: I'M RAISING MY HAND WHILE HOLDING THE MIC. IT'S ONE THING AND KIND OF IN THE WEEDS FOR 15 MINUTES, 15 DAYS AND THEN YOU KNOW IT'S COMING OUT WITH THESE DEVICES THAT WERE DESIGNED A TRIP ON THE CORTICAL SURFACE AND HAVING A THIN FILM SOUNDS BETTER THAN HAVING PENETRATING -- THAT'S COMMON SENSE WITHOUT DATA BUT WHEN PEOPLE ARE HAVING APPROVED PROTOCOLS WHERE YOU PUT A DBS SLEET IN AND THERE'S NO EXPERIENCE AND YOU'RE USING THE SAFETY OF THE TIME IN THE O.R. OR EVEN A MONTH. AND WE ACTUALLY ARE FLYING BLIND. YOU THINK IT'S GOING TO WORK ANYWAY AND YOU HAVE A THREE-MONTH OR SIX-MONTH TRIAL WILL YOU TAKE IT OUT LATER. WE HAVE PEOPLE WITH DBS SLEEVES SINCE 2003. IT'S NOT LIKE PARKINSON'S WHERE THEY DIE WITH THE PROGRESSIVE DETERIORATION OF THEIR UNDERLYING DISEASE. THEY HAVE PERMANENT FUNCTIONING LEADS. AND WITH THE DBS SLEEVE IT SEEMS TO BE NO HARM, NO FOUL AND THAT'S A SCIENTIFIC QUESTION. WHEN THE BATTERY DIES YOU HAVE TO REPLACE IT SO YOU NEED TO KEEP IT ON. THE IDEA OF A CORTICAL STRIP SEEMS LIKE A WHOLE NEW BALL GAME IF PUT IN TO ENHANCE A DBS SLEEVE OR A SENSOR. HOW DO WE GET THE DATA TO PLAN? >> IT'S A GREAT QUESTION. >> AND AGAIN PUTTING THAT IN ACUTELY, MAYBE NO BIG DEAL EXPERIENCED HANDS. OF THE SERIES THERE'S TWO THEY ABORTED BECAUSE THEY FELT RESISTANCE, MAYBE A VEIN AND THERE'S NO ADVERSE EVENTS IN THE STUDY. SUPPOSE THE TRIAL'S OVER AND IT'S A YEAR LATER AND YOU'LL EX-PLANT THE SYSTEM. I'D BE NERVOUS ABOUT DRAGGING A STRIP ACROSS THE BRAIN THAT'S BEEN THERE A YEAR FOR SURE. >> Question: I APPRECIATE YOUR TALK. I TAKE EXCEPTION WITH THE NO-ZERO RISK AND INVITE YOU TO THINK MORE ABOUT THAT. WHEN THERE'S IDENTIFIABLE DATA YOU HAVE -- >> IT'S IN QUOTES. >> BUT THE FINDINGS ARE THAT YOU MAY CAUSE OVERTREATMENT YOU DIDN'T INTEND TO OR PRIVACY ISSUES. I'D BE CONCERNED EQUALLY ABOUT IN ZERO RISK BECAUSE I THINK THERE MAY BE REAL CLINICAL RISK PARTICULARLY FOR AN RNS LIKE THE EPILEPSY ONE WHERE THEY'RE CONSTANTLY MODULATING AND CHANGING IT. WHAT'S THE IMPLICATION FOR FIDDLING WITH THAT AROUND CLINICALLY. THESE ARE THINGS I'D ENCOURAGE YOU TO RETHINK THE USE OF EVEN ANY ZERO RISK. DEF >> OKAY. TIME FOR A BREAK. >> THANK YOU FOR LETTING ME JOIN REMOTELY. WE WROTE A PAPER WITH A SUMMARY OF WHAT A PATIENT IN GENERAL CAN EXPECT OF STIMULATION FOR MOVEMENT DISORDERS AND THE TECHNICAL CHOICES HOW TO DO THE PROCEDURE. IT WAS SPECIFICALLY WRITTEN FOR NON-NEUROLOGISTS AND NEUROSURGEONS AND WRITTEN FOR GENERAL PRACTITIONERS AND THE GENERAL PUBLIC. YOU CAN DOWNLOAD IT FOR FREE FROM PUB MED. IF YOU CAN ADVANCE ONE SLIDE MORE. THIS IS THE LIST OF RISKS I WOULD LICK TO DISCUSS IN THE NEXT TEN OR 15 MINUTES. THIS WILL BE THE SEGUE FOR THE NEXT SPEAKERS TO ARTICULATE THEY'RE POINTS TO HAVE THE DISCUSSION TO FOLLOW. THE INTENT HERE IS TO ASK THE AUDIENCE TO THINK THROUGH THIS WITH ME AND IMAGINE THE POSITION OF INVESTIGATIVE TEAM AS WELL AS MEMBERS OF THE I -- IRB THINKING THROUGH THE RISKS OF A CLINICAL TRIAL THAT'S GOING TO BE DONE WITH A NOVEL DEVICE OR A CLINICAL TRIAL THAT'S GOING TO BE DONE WITH AN EXISTING DEVICE FOR A DIFFERENT INDICATION POTENTIALLY TARGETING A DIFFERENT AREA OF THE NERVOUS SYSTEM. WE IMPLANTED THE SYSTEM AND WE TALKED ABOUT THIS MOMENTS AGO. THE RISK OF DELIVERING ELECTRICAL STIMULATION OF A CLINICAL TRIAL RISKS RELATED TO THE FINANCES OR THE PATIENT'S FINANCES OR THE PATIENT'S FAMILY FINANCES. I'LL ARTICULATE MORE ON THAT IN A MOMENT. RISK RELATED TO THE NOVELTY OF THE DEVICE. RISK RELATED TO THE OUTCOME OF THE RESEARCH. I'LL EXPLAIN THAT IN A MOMENT AGAIN. THE OVERALL RISKS ASSOCIATED WITH PARTICIPATING IN THE PROCESS OF SCIENCE AND DISCOVERY AND FINALLY I'D LIKE TO THINK OF THE RISK OF THE UNFORESEEABLE WHEN WE ARE STEPPING INTO THE BOUNDARIES OF KNOWLEDGE AS MUCH AS WE MAY THINK ALL THE POSSIBLE RISKS I THINK AS A GROUP, AS' -- AS A SOCIETY WE HAVE LEARNED SOME RISKS WE'RE NOT INFORMED ENOUGH TO ANTICIPATE WHAT THEY WILL BE. AND THOSE TO ME ARE THE BIG QUESTION MARKS WHEN DESIGNING A STUDY. AND WITH A LITTLE TALK ABOUT THE RISK OF SURGERY. HEMORRHAGE IN MANY PARTS OF THE BODY CAN BE DRAINED. HEMORRHAGE IN THE BRAIN IS ALSO A STROKE. STOKES CAN BE SMALL AND RECOVERABLE. STOKES CAN BE LARGE SOMETIMES DEVASTATING. THERE'S A RISK OF INFECTION. A RISK OF EROSION THROUGH THE SKIN OF THE HARDWARE. THERE'S A CHANCE OR A RISK THE SURGICAL TEAM WILL NOT REACH THE OPTIMAL PLACEMENT OF THE ELECTRODE OR ARRAY IN THE FIRST SURGERY AND ADDITIONAL WILL BE REQUIRED. YOU NEED TO CONNECT THE WIRES RUNNING DOWN IT NECK TO BE ABLE TO PULL A WIRE FROM THE CHEST OR HEAD AND IS THERE A COMMON RISK HERE? NO. IT'S RARE TO HAVE A COMPLICATION BUT THERE'S A RISK TO THE THORAX, TO THE LUNGS AND HEMORRHAGE IN THE CHEST OR DIRECT INJURY TO THE LUNGS. AND IF THERE'S A SICKER POPULATION OR ELDERLY POPULATION WE NEED TO CONSIDER THE RISK OF POST-OPERATIVE MORBIDITY AND THEY EXIST DURING AN EXPERIMENTAL PROCEDURE. RISK OF A HEART ATTACK OR RESPIRATORY PROBLEMS BEFORE AND AFTER SURGERY. DURING SURGERY AND RISKS MUCH THROMBOSIS FROM EMBOLI WITH HAVE SEEN THE RISKS I HAVE LISTED HERE THOUGH THEY ARE MOSTLY UNCOMMON. WHEN WE DO STIMULATION FOR SAY PARKINSON'S DISEASE WE ALWAYS ENCOUNTER SIDE EFFECT. THAT'S A LITTLE BIT BY DESIGN. WE TRY TO IDENTIFY THE SIDE EFFECT AND STAY AWAY FROM THOSE. THE BIGGER RISK IS THE RISK OF CHRONIC STIMULATION WHEN WE DO NOT DETECT A PROBLEM ACUTELY AND WE LET THE PROBLEM PROCEED OVER TIME. FOR EXAMPLE, THERE'S A KNOWN RISK WHEN WHEN WE DO DBS FOR A KNOWN DISEASE LIKE PARKINSON'S AND COGNITIVE CHANGES AND WHY WE SCREEN PATIENTS FOR COGNITIVE PROBLEMS BEFORE SURGERY BECAUSE HAVING COGNITIVE PROBLEMS BEFORE SURGERY AMPLIFIES PROBLEMS. WHEN WE ARE SUCH RESEARCHING THERE IS AN INHERENT RISK OF MOTOR COGNITIVE BEHAVIORAL PROBLEMS THAT WE MAY OR MAY NOT BE ABLE TO DETECT AND WE MAY NOT BE ABLE TO DETECT IN A TIMELY FASHION. I THINK THERE'S A RISK THAT NEEDS TO BE CONSIDERED AND DISCLOSED. THERE'S A QUESTION MARK ABOUT PERSONALITY CHANGES. THIS IS THE TOPIC OF NEW RESEARCH AND IT IS IN FACT THE ENTIRE GOAL OF A NEW GRANT BY ONE OF MY PARTNERS HERE AT CLEVELAND CLINIC WHO WILL BE FORMALLY EVALUATING CHANGES BEFORE AND AFTER STIMULATION. IN PRINCIPLE, SIDE EFFECTS OF STIMULATION ARE REVERSIBLE. YOU CAN ADJUST AND THE ADVERSE EFFECTS SHOULD BE CHANGED. I QUESTION SOMETIMES, DEPENDING ON THE APPLICATION, AND I'LL GIVE AN EXAMPLE OF THE APPLICATION FOR TOURETTE SYNDROME WHETHER THERE POSSIBLE LIFE EXPERIENCES THAT WILL BE IRREVERSIBLE. AND IN PARTICULAR RELATED TO KIDS OR YOUNG ADULTS. ONE OF THE KNOWN SIDE EFFECTS OF DOING THE SURGERY IN PATIENTS WITH TOURETTE SYNDROME THAT HAS BEEN VERY WELL EVALUATED BY OUR COLLEAGUES IN THE NETHERLANDS IS OF A CHANGE IN LIBIDO IN SEXUAL FUNCTION FOR YOUNG MALES. I POSTULATE THAT EVEN IF WE CAN REVERSE THE STIMULATION IS THAT UNDERGOING THIS MANY YEARS MAY HAVE AN IRREVERSIBLE BY THE MATURING OF THE BRAIN AND INDIVIDUAL UNDERGOING CHRONIC STIMULATION. IF I CAN GO ONE MORE SLIDE. THERE'S RISK RELATED TO THE PATIENT'S AND FAMILY'S FINANCES WHEN, FOR EXAMPLE, TAKING ON A PATIENT AND HE'S USING THE STUDY AS AN OPPORTUNITY TO HAVE INSURANCE BECAUSE OF LIMITED INSURANCE OR NO INSURANCE AT ALL. AND IF COMPLICATIONS ARISE DURING THE PROCEDURE AND BEYOND THE NIH FUNDED STUDY OR FOUNDATION, THAT FAMILY AND THE INSURANCE OF THAT FAMILY MAY BE ON THE HOOK FOR COVERING THE COSTS ASSOCIATED WITH CONSEQUENT CAL CARE. IF I CAN GO -- MEDICAL CARE. IF I CAN GO ONE MORE SLIDE. THIS IS REGARDING NEW DEVICES. DEVICES THAT ARE NEW AND STILL IN THE EXPERIMENTAL PHASE ARE PROTOTYPES AND SOMETIMES HANDMADE OR OUTSIDE OF A STANDARD ASSEMBLY LINE AND HAVE AN INHERENT RISK FOR FAILURE OR MALFUNCTION AND THE POTENTIAL RISKS ASSOCIATED WITH ADDITIONAL SURGERY I DISCUSSED. THIS IS A COMMON TOPIC IN OUR GROUP. WE HAVE SEEN INTERESTING COMPLICATIONS DUE TO A CLINICAL TRIAL. FOR EXAMPLE, A PATIENT WHO IS PARTICIPATING IN A CLINICAL TRIAL AND DOES NOT RESPOND BUT THE OVERALL CLINICAL TRIAL IS POSITIVE. THE THERAPY MOVES ON AND BECOMES A STANDARD. IT BECOMES FDA APPROVED. BUT THAT PATIENT IS LEFT BEHIND BEING FOR EXAMPLE ONE OF THE FEW NON RESPONDERS AND FEELING RATHER HOPELESS AT THIS POINT THAT EVEN THE NEW THING WAS NOT GOOD ENOUGH OR EFFICACIOUS ENOUGH TO PRODUCE A BENEFIT TO THIS PERSON WHILE IT WAS BENEFICIAL TO THE REST OF THE POPULATION. AND IN A NON-FEDERALLY FUNDED STUDY WHERE WE HAD PATIENTS WHO RESPONDED OR FELT BETTER WITH STIMULATION IN THE CONTEXT OF AN OVERALL FAILED CLINICAL TRIAL. THE OUTCOMES OF THE CLINICAL TRIAL DID NOT CORROBORATE AN ORIGINAL HYPOTHESIS BUT SOME PATIENTS DID IMPROVE AND WHO ARE NOW UNDER THE IMPRESSION OR BELIEF OR EFFECT THAT THE INTERVENTION DRAMATICALLY IMPROVED THEIR LIVES. ONE CAN BE IN A TRICKY SITUATION WHERE THE SPONSOR IS NO LONGER INTERESTED IN THE CONTINUATION OF THE STUDY. MAY WANT THE DEVICES EX PLANTED OR THE STUDY TERMINATED AND THE PERSON IS NOW LEFT WITH AN UNSUPPORTED BRAIN DEVICE THAT IS THOUGHT TO BE EFFICACIOUS FOR AT LEAST THAT ONE INDIVIDUAL. YOU SEE THE LAST ONE. IF YOU CAN MOVE ON TO THE NEXT ONE IT SAYS RISK OF SCIENCE AND DISCOVERY. DR. SHETH WAS TALKING ABOUT THE ADDITIONAL MEASURES THAT WE TYPICALLY ADD CRIN CLINICAL TRAIL. THIS IS COMMON IN BRAIN INITIATIVE STUDIES AND TRUE FOR THE STUDY IN CLEVELAND UNDER THE BRAIN INITIATIVE IN EVALUATING THE EFFECTS OF DBS FOR STROKE, MOTOR REHABILITATION. WE ADD SOME PHYSIOLOGICAL MEASURES TO NOT ONLY OPTIMIZE THE THERAPY THAT WE'RE INVESTIGATING BUT ALSO UTILIZE THE STUDY AS A WAY TO BETTER UNDERSTAND THE NEUROPHYSIOLOGY IN THE DISEASE STATE IN THE POST-STROKE STATE BELIEVING SCIENCE IS ALWAYS RELEVANT AND SCIENCE WILL ALWAYS INFORM EITHER OUR OWN GROUP OR OTHER GROUPS ON HOW TO DEVELOP THE NEXT THING REGARDLESS OF WHETHER THIS ONE IS EFFICACIOUS OR NOT. AND THERE ARE RISKS TO THOSE PHYSIOLOGICAL MEASURES THAT HAVE NO THERAPEUTIC INTENT. I THINK WE NEED TO STILL USE THEM. WE NEED TO LEARN AS MUCH AS WE CAN WHEN WE UTILIZE THE BRAIN INITIATIVE DOLLARS. THE TAXPAYER DOLLARS TO DO A CLINICAL TRIAL. IT'S IN US TO LEARN THE MOST WE CAN TO BETTER INFORM THE FUTURE OF NEUROSCIENCE BUT THERE'S RISK TO THE INDIVIDUALS UNDERGOING THOSE DATA COLLECTION EVEN IF THE RISKS ARE CONSIDERED TO BE MINIMAL. THE NEXT ONE IS THE LAST SLIDE AND A QUESTION MARK ON PURPOSE BECAUSE I DON'T KNOW THE UNFORESEEN. IF YOU KNOW THEN IT'S NOT UNFORESEEN. AND WE CAN ALWAYS LEARN SOMETHING WE'RE NOT EXPECTING. SOMETIMES WE LEARN GOOD THINGS. SOMETIMES WE LEARN BAD THINGS. I WOULD LIKE TO STOP NOW AND THANK THE ORGANIZING COMMITTEE FOR NOT ONLY ME TO START THE SESSION AND I APOLOGIZE FOR NOT BEING THERE IN PERSON TODAY. [APPLAUSE] . >> THANK YOU. ANDRE. NEXT UP WE HAVE PAUL FORD. >> I IN THE GROUP AND I PROVIDE MONITORING AND HOW DO I REASSURE THE SUBJECTS CAN GET SUPPORT AND HE MEETS WITH THEM AND I DON'T REPORT TO DR. MACHADO. WE COLLABORATE. I TRY TO LEARN AS MUCH AS I CAN. SO WINSTON FRAMED IT NICELY SOME OF THE THINGS I WANT TO TALK ABOUT WHEN HE PUSHED ON THE ISSUE OF MAYBE WE NEED TO BE TALKING ABOUT SPECIFIC RISK ABOUT THINGS. THIS IS ALREADY SET UP TO TALK ABOUT MY BELIEF AND I'LL TRY TO ARGUE INVASIVENESS IS A WRONG METRIC. WE SEE THIS EVEN IN HOLLY'S QUESTION AND ANSWER SESSION WHERE WE HAVE THE INVASIVE AND NONINVASIVE IN ONE GROUP. I'M GOING TO TALK ABOUT HARM, PERMANENCE AND TABOO. I LOOK FORWARD TO YOUR SUGGESTIONS. HANK, A COUPLE WEEKS AGO IN PITTSBURGH HAD WONDERFUL REFLECTS ABOUT THE CELEBRATION OF FRANKENSTEIN AND I JUST WANT TO IN PASSING SAY I THINK THIS SAY WONDERFUL THING TO REFLECT ON PARTICULARLY ABOUT TABOOS IT'S A TIME OF DEAD BODIES AND GRAVES AND EMERGENCE OF TECHNOLOGY WITH THE FILM AND WITH THE BOOK AND LATER WITH FILM HIGHLIGHTING OUR VISCERAL RESPONSES TO NEW TECHNOLOGIES. I TAKE THE FRANKENSTEIN'S MONSTER AT THE CORE WITH A MEANING MAKING EXISTENTIAL MEANING OF THE NEW LIFE AND REFREKS OF A CORE I THINK WE SHOULD BE THINKING ABOUT WHEN WE THINK ABOUT INVASIVENESS. I DID MY TRAINING ORIGINALLY IN SOLID ORGAN TRANSPLANTATION AND THERE WAS A FACTOR MAYBE IF I HAVE SOMEONE ELSE'S HEART IN ME I'LL FEEL LIKE I'M NOT ME AND WHAT IF A MAN HAS A WOMAN'S HEART AND IT TURNED OUT THAT REALLY ALL THOSE URBAN MYTHS OF A HAND TRANSPLANT HAVING ITS OWN MIND WERE FEARS AND CONSTERNATION BUT WHEN IT COMES TO IT THEIC FACTOR SHOULDN'T BE DRIVED WHAT WE DO. I THINK AT TIMES WE USED THIS INVASI INVASI INVASI INVASIVE CYBORG ABOUT OUR FEARS IN CHANGE. WE DON'T IDENTIFY OURSELVES AS AN ISOLATED INDIVIDUAL TOM-TOM. WE'RE NETWORK OF PEOPLE. WE GRIEF SOMETIMES THE LOSS OF PETS. SOMETIMES WE GRIEF A LOSS WE'VE HAD 20 YEARS AND NICKNAME IT. WE IDENTIFY IN A CERTAIN WAY AND ADDRESS A CERTAIN WAY OR HAIR IN A CERTAIN WAY WE BECOME EMOTIONALLY ATTACHED TO THESE. FOREIGN OBJECTS ARE OFTEN INTEGRATED INTO PEOPLE'S BODY AND BECOME THEM. I HAD AN INTERN WITH US WHO HAD AN EPILEPSY SURGERY AT 16. I GOT HER TO REFLECT ON HER EXPERIENCES. SHE GOT THROUGH COLLEGE AND HAD SOME CHALLENGES BECAUSE OF THE EPILEPSY SURGERY BUT SHE WAS SEIZURE SO -- I THINK WE NEED TO BE CAREFUL WHEN WE PULL OUT QUALITATIVE QUOTES. I FEEL LIKE A CYBORG. THAT IS TRUE AND REAL EXPERIENCE OF THAT PERSON. BUT THERE MAY BE ANOTHER PERSON WE DIDN'T TALK TO WHO SAYS, WOW, I FEEL SO INDEPENDENT NOW I FEEL LIKE ME. SO UNDERSTAND WE TRY TO GET THE DIVERSITY OF EXPERIENCES AND UNDERSTAND THE HARMS AND BENEFITS AND RISKS. LEAST INVASIVE HAS THE RIGHT FEEL. I DONT USUALLY GO TO DICTIONARIES FOR THINGS BUT I START TO THINK ABOUT WHAT INVASION REALLY MEAN AND IT SNEAKS INTO THE CONCEPT OF VIOLATION. THE IN COMING OR SPREAD OF SOMETHING HURTFUL. ALREADY RATHER THAN SAYING WE'RE GOING THROUGH A BODY -- PENETRATING A BODY, WE HAVE ALREADY WRAPPED IN AND TALKED ABOUT THE INVASION, RIGHT, SO WE NEED TO BE CAREFUL. WE DON'T USE THAT WHEN WE TALK ABOUT SORT OF NEUROPSYCHIATRIC DRUGS. WE DON'T TALK ABOUT ANTIDEPRESSANTS AS AN INVASION IN THE NEUROCHEMICAL CIRCUITRY OF MY BRAIN. IT TAKES AWAY SELF. I THINK IT'S USED AS A SURROGATE. I BELIEVE IT'S USED AS A SURROGATE FOR THINGS LIKE HARM AND RISK. I THINK WE OFTEN USE IT IN SHORT FORM BUT FORGET WE HAVE CONNOTATIONS THAT NOW DRIVE US. THERE'S A STIGMA OF A NEUROLEPTIC MEDICATION. WE THINK OF THE MEDICATIONS AS NON INVASIVE BUT THEY CAN HAVE NON REVERSIBLE EFFECTS. DR. MACHADO AND I HAD A PATIENT TOGETHER WHO ENDED UP HAVING DEEP BRIAN STIMULATION WITH THIS KINISIA WITH A PILL AND IT'S WAS WRONGLY THOUGHT OF. SO THE HIGH-FREQUENCY ULTRA SOUNDS. THESE ABLATION AND YOU CAN TELL WITH MY EARLIER QUESTION I'M CONCERNED WITH HIDDEN OR DIFFICULT TO DETECT SYMPTOMS. I HERE OF BRAIN INJURY 20 YEARS AGO AND YOU CAN THINK THEY'RE CONNECTED. THINK OF POST-TRAUMATIC STRESS DISORDER. OFTEN THEY CAN HAVE NO HARM TO THE BODY YET THEY'RE DEVASTATING CONSEQUENCES. WITHOUT SUBSTANTIAL HARM FOR INVASIVENESS WE CAN INDUCE BIG HARMS WE WANT TO AVOID. SOMETIMES DBS STACKS UP FAVORABLE TO THE RISKS OF OTHER MODALITIES. SOMETIMES THEY'RE LESS RISKY. I WAS PLAYING WITH THE SLIDE AND YOU CAN SEE I'M INFLUENCED BY DR. MACHADO MAYBE WE DO NEED TO PUSH BACK ON SOME DEVICES TO SAY IN WHAT WAY SHOULD WE BE CONCERNED WITH WHETHER THIS FORECLOSES OUR OPEN FUTURES OR HAS PERMANENCE. I'M MORE COMPELLED WHEN PEOPLE SAY YOU'LL ONLY BE ABLE TO GET AN MRI IF YOU HAVE A DBS LEFT IN AND IT'S A PERMANENCE THAT MATTERS. YOU CAN UNDO THE THERAPY. AND IN TOURETTE MAYBE YOU ARE CHANGING THE BRAIN IN A WAY WHERE YOU CAN'T REVERSE THE DEVELOPMENT CHANGE. I'M TOLD BY NEUROSURGICAL COLLEAGUES THAT REMOVE VAGAL NERVE STIMULATERS THEY REMOVE THE COIL. THEY EXPLANTED THE CORD BECAUSE IT'S ENGRAPHED OR WHATEVER IT DOES AND IT WOULD BE RISKIER TO GET IT OUT AND YOU CAN CAUSE SEVERE DAMAGE SO SOME OF THESE THINGS, IF THEY GET IMMESHED IN WAYS MAY NOT BE AS REVERSIBLE AS WE THINK. SO I MAINTAIN WE SHOULD BE THINKING AND CONCERNED ABOUT HOW RESEARCH CHANGES THE FUTURE POSSIBILITIES. PEOPLE WITH THESE DEVICES. SO AGAIN, NOW MAY BE IT'S ON TRANSCRANIAL DIRECT STIMULATION WE CAN HAVE THIS. THE ONE CAVEAT WHERE IT MAKES SENSE TO ME IF YOU'RE GOING DO BUY IN THERE'S A TABOO SOME SACREDNESS OF BODIES BEING PENETRATED IN CERTAIN WAYS. IF YOU HOLD THIS BELIEF SYSTEM I CAN UNDERSTAND HOW INVASIVE AND NONINVASIVE MATTERS. BUT WHETHER IT'S TRANSCRANIAL STIMULATION, DISTRICT STIMULATION, ECT THEY'RE INVASIVE BECAUSE THAT GO INSIDE THE BODY. IT'S HARD TO DEFEND THIS TABOO VIEW ON A SCIENTIFIC BASIS AND WOULD HAVE TO BE A SPECIFIC WORLD VIEW SET OF VALUES THAT WON'T APPLY TO THE VAST MAJORITY OF THE WORLD. I THINK WE NEED TO OFFSET THE UNREFLECTIVE TABOOS AND STIG SMAS. WE HAVE A -- STIGMAS. WE HAVE A RESPONSIBILITY TO PUSH BACK AGAINST THE VISCERAL LANGUAGE. WE SHOULD BE CONCERNED WITH RESEARCH IN THE FUTURE AND ACCOUNT FOR STIGMA AND TABOOS AND IT'S OUR OBLIGATION AS RESEARCHERS TO WORK WITH IRBs AND MEDIA TO CONTINUE EDUCATING THEM ON THESE THINGS SO THEY MAKE WELL REASONED REPORTS AND OVERSIGHT. THANK YOU. >> I FORGOT TO SAY BEFORE THE PLAN WAS WE'D GO THROUGH ALL THE PRESENTATIONS AND HAVE QUESTIONS AT THE END. PEOPLE ARE NODDING. SEEMS OKAY. ALL RIGHT. THANK YOU, PAUL. THAT WAS GREAT. SO WE HAD TWO PEOPLE VERY TIMELY. I FORGOT TO SAY ALSO I WAS GOING TO INDICATE WHEN TIME WAS RUNNING OUT BUT I DIDN'T NEED TO FOR EITHER OF YOU. NEXT WE HAVE JOE FINS WHO IS GOING TO ABOUT DBS -- I FORGET YOUR TITLE. >> I'M IN NO MAN'S LAND. >> THANK YOU VERY MUCH. SO WHAT I WAS ASKED TO DO AND IT WASN'T INITIALLY MY CHOICE WAS TO PROVIDE A HISTORICAL FRAME ON THIS TO TALK ABOUT OUR WORK IN THE DILEMIC DBS STUDIES AND WHAT HAS TO BE DE CONSTRUCTED IN DOING THIS WORK. I WROTE MY FIRST PAPER I THINK ON AN ETHICAL FRAMEWORK FOR THE DBS STUDY IN 2000. IT WAS ACTUALLY 1999. DURING THAT BIG SNOW STORM THAT HIT VIRGINIA AND I WAS MAROONED IN A CABIN ON A COLLEGE CAMPUS AND WROTE THIS PAPER TALKING ABOUT THE IT AND I WAS STRUCK HOW 17 YEARS WAS TRYING TO FIND WHERE THEY WERE PERMISSIVE OR OPEN TO ALL OF THIS TWO DECADES AGO. THIS WAS A NON STARTER AND WHAT WE PROPOSED TO DO WAS ALMOST IMPOSSIBLE AND FROM A REGULATORY STANDPOINT ALSO CHALLENGING. SO WE PUBLISHED THIS PAPER IN NATURE IN 2007 AND I WANT TO TELL YOU THE STORY WHAT WE HAD TO OVERCOME. THERE WAS A LOT OF INTEREST IN PEOPLE WHO HAD LATE RECOVERY FROM THE MINIMALLY CONSCIOUS STATE REGAINING CAPACITY FROM DRUGS AND WAYS TO AUGMENT THE PROCESS AND ONE THING MY COLLEAGUE INVISIONED -- ENVISIONED WAS THE STUDY AND IT WAS A PHASE 1 STUDY. THERE WAS NO PROSPECT OF DIRECT MEDICAL BENEFIT. IT WAS MORE THAN MINIMAL RISK AND WE HAD A PATIENT WHO HAD DECISIONAL INCAPACITY. YOU THINK FROM ALL THOSE VARIABLES THIS WAS A NO-GOOD SITUATION. WE WORKED ON SURROGATE CONSENT. WE ALSO AVOIDED THE THERAPEUTIC MISCONCEPTION THAT FRAMING IT AS A THERAPEUTIC ENDEAVOR BECAUSE IT WOULD HAVE BEEN DISINGENUOUS IN A PHASE 1 STUDY AND I SPENT A DECADE TRYING TO MAKE THE GRANDM GRANDMAS TO MAKE THE STUDY HAPPEN. THERE ARE TWO CHALLENGES. ONE WAS THE LEGACY OF FUTILITY AND THE NOTION THAT ALL SEVERE BRAIN INJURY WAS INVARIABLY FUTILE AND THE LEGACY OF THE RIGHT TO DIE MOVEMENT COMING OUT OF SEVERE BRAIN SURGERY. MOST RECENTLY SHIVO THAT ONCE THE BRAIN SO SEVERELY INJURED WOULD NEVER BE THE TEMPLATE FOR IMPROVEMENT. THEN THE FALSE ANALOGY TO PSYCHO SURGERY AND HOW NEURAL -- NEURNEUROMODULATION AND THERE WAS AN ARTICLE ABOUT THE NUMBER OF SACRILEGE TO INTERVENE IN THE BRAIN WITH ABLATION. THERE WERE DIFFERENCES THAT MADE A DIFFERENCE. THE RIGHT TO DIE MOVEMENT EVERYBODY KNOWSMOVEMENMOVEMEEVERYBODY KNOWS THIS WAS AS THE RIGHT TO BE LEFT ALONE. IN THE QUINLAN THEY INVOKED THE VEGETATIVE STATE FROM '76 BASED ON THE JUDGE'S ORDER. IT WAS THE LOSS OF THE SAPIEN STATE FOR QUINLAN'S VEN VENTILATOR TO BE REMOVED. THE LOSS OF THE COGNITIVE SAPIEN STATE GOT GENERALIZE TO OTHER BRAIN STATES AND THE VEGETATIVE STATE BECAME THE ULTIMATE MEDICAL FUTILITY. THEY WERE IMMUTABLE. IF YOU READ THE QUINLAN AUTOPSY REPORT THE BRAIN WAVES WERE HALF THE NORMAL. THIS WAS NOT THE SUBSTRATE FOR THE STATE AND WE DEVELOPED THIS NEGLECT SYNDROME FOR OTHER POPULATION OUT OF OUR GAZE AND THERE WAS A NEW CATEGORY EMERGING CALLED THE MINIMALLY CONSCIOUS STATE. THESE GUYS WERE SORT OF CONTAMINATED WITH THE PRE PRESUMPTION OF FUTILITY AND IT MINIMALLY VEGETATIVE STATE WAS IN 2002 AND THE DISTINCTION IS THEY'RE CONSCIOUS THOUGH THEY CAN TRACK YOU IN THE ROOM AND SOMETIMES SAY THEIR NAMES BUT THEIR BEHAVIORS ARE EPISODIC AND INTERMITTENT AND IN NURSING HOMES IN A STUDY 41% OF PEOPLE AND THE IDEA OF WHAT FOLKS ARE TRYING TO DO IS THAT ONCE SOMEBODY IS IN A MINIMALLY CONSCIOUS STATE THEY'RE ON A TRAJECTORY. TERE'S NO TIME COEFFICIENT ON THIS. NOT THE LONGER YOU'RE IN THE MINIMALLY CONSCIOUS STATE THE WORSE IT WILL BE BUT YOU HAVE THE POTENTIALITY AND THE QUESTION WAS HOW DO YOU TACT THEM. THERE WAS A PHYSIO LOGIC BASIS AND WHEN THE WORK WAS COMING OUT THERE WERE THOUGHTS OF CYBORGS AND MIND CONTROL AND LOBOTOMIST AND IS THIS IS HOW PEOPLE WERE THINKING ABOUT THEM. AND THEY LOOKED AT PUBLIC CONTROL TO QUELL THE VIOLENCE IN SOCIETY. THOSE WERE ROUGH TIMES. HERE PSYCHO SURGERY FOR SOCIAL CONTROL IS HIGHLY UNLIKELY SIMPLY BECAUSE THERE'S NOT ENOUGH NEUROSURGEONS. THERE WAS A REPORT LOST IN THE ARCHIVES. I WROTE A PIECE ABOUT THAT IN 2003 BECAUSE I FELT I HAD TO GO BACK AND UNDERSTAND THE HISTORY TO BE AN ADVOCATE FOR THE DIFFERENCE FOR THE WORK WE WERE DOING. THIS WAS A REPORT PUBLISHED IN '77 THEY CALLED FOR, NOT A BAN, BUT AN ETHIC THAT WAS THERAPEUTIC BUT NOT PUNITIVE, NO LAW ENFORCEMENT OR ENHANCEMENT AND CALLED FOR A MECHANISM FOR SURROGATE CONSENT. KEN RYAN, AN OB-GYN AND CHAIR OF THE NATIONAL COMMISSION SAID IN AN INTERVIEW THE YEAR BEFORE IT WAS PUBLISHED IN SCIENCE WE LOOKED AT THE DATA AND SAW THEY DID NOT SUPPORT OUR PREJUDICES. I DID NOT EXPECT TO COME OUT IN FAVOR OF PSYCHO SURGERY BUT WE SAW SICK PEOPLE HAVING HELPED BY IT AND DIDN'T DESTROY THEIR INTELLIGENCE AND THEIR MARRIAGES WERE INTACT. THE OPERATION SHOULD NOT BE BANNED. AND THEY DIDN'T BAN IT BUT ALSO SAID IT SHOULDN'T BE AND ACCEPTED PRACTICE AND RECOMMENDED AN ADVISORY BOARD FOR VULNERABLE POPULATION AND SAID THERE SHOULD BE IRB REVIEW THAT IS UNTIL SAFETY AND EFFICACY IS ESTABLISHED TO ESTABLISH THE COMPETENTNESS OF THE SURGEON AND INFORMED CONSENT AND MAKE SURE THERE'S NO CORERI CORERING -- COERCION. NOW, ONE OF THE CHALLENGES WE HAD WAS THAT THESE ARE VULNERABLE POPULATIONS. THEY CAN'T GIVE CONSENT. IT'S INVASIVE AND MORE THAN MINIMAL RISK. THE QUESTION ASKED EARLIER, WE NEED TO HARMONIZE THE CATEGORIES OF RISK. THE IDEA IS -- THE MAJOR ISSUE IS THAT I THINK IN THIS CASE WHAT WE HAD TO UNDERSTAND WAS WE WERE CONFLATING RESPECT FOR PERSONS WITH INFORMED CONSENT IT'S ONE THING TO GIVE INFORMED CONSENT WITHOUT INFORMED CONSENT THEN TO TRY TO DEMAND INFORMED CONSENT WHEN THE OBJECT OF THE INTERVENTION IS TO RESTORE THEIR AGENCY AND PARTICIPATE IN DECISIONS IN SOME WAY. AND WE WERE SUCCESSFUL. INSTEAD OF THE ARGUMENT BE PERCEIVED AS THAT MAKES SENSE WOULD HAVE BEEN CONDEMNED. WE DON'T WANT TO CONDITION THE QUALITY OF THE ARGUMENT TO THE OUTCOME OF THE STUDY. WE ENGAGED IN A ROBUST CONSENT PROCESS AND TRIED TO AVOID A THERAPEUTIC MISCONCEPTION AND WORKED WITH A REPRESENTATIVE AND WROTE IN THE PROTOCOL IF THE OF WERE TO EVER REGAIN DECISION-MAKING CAPACITY WE'D SEEK THEIR ASCENT OR CONSENT TO CONTINUE. WE ALSO ENGAGED AN REGULATORY OVERSIGHT AND HAD MULTIPLE IRBs AT THE VARIOUS INSTITUTIONS INVOLVED. WE HAD AN ETHICS AND SCIENCE POSTER. AND I THINK ONE OF THE THINGS THAT WAS ALSO IMPORTANT AND THE NOTION OF BIOMARKERS AND SCIENTIFIC DESIGN TO DETERMINE A STRUCTURE WITH A VIEW TO THE DISCOVERY OF FUNCTION HAS BEEN THE FOUNDATION OF PROGRESS. THINK WE HAVE TO UNDERSTAND BIOMARKERS. WE NEED A HYPOTHESIS-GENERATING QUESTION AND WE WANT TO AVOID THE FALSE ANALOGY AND THE FALSE DISTINGUISHING MODULATION FROM ABLATION AND SAY WE CAN LOCALIZE BETTER AND THIS IS REVERSIBLE. WHEN WE DESIGNED OUR STUDY, WE DID IT IN A MANNER TO FOCUS ON THE MINIMALLY CONSCIOUS STATE. WE WANTED TO GO FUNCTIONALLY AS LOW AS POSSIBLE WITHOUT HAVING THE FEASIBILITY OF WORKING BUT NOT TO GO SO HIGH WHERE WE CAN HAVE INCREMENTAL HARM. AND NOW PEOPLE HAVING DEMONSTRATED PRINCIPLE WHERE WE DEMONSTRATED PROOF OR PRINCIPLE. MOST OF YOU KNOW THE STORY BUT A PATIENT WHO WE REPORTED ON HAD A SCALE OF 3 WAS UNABLE TO TALK OR EAT WITHOUT A FEEDING TUBE AND INCONSISTENT COMMAND OF HIS EYE MOVEMENT AND THE HIGHEST LEVEL OF RESPONSE. WITH THE DEEP BRAIN STIMULATION HE COULD SAY SIX OR SEVEN WORD SENTENCES AND TELL HIS MOTHER HE LOVED HER AND GOOD TO OLD NAVY AND PICK OUT A SHIRT HE DESIRED. I DESCRIBE THIS IN MORE DETAIL IN MY BOOK. HE ALSO HAD IMPROVED LUNG CONTROL AND FOR THE FIRST TIME IN SIX YEARS WAS ABLE TO EAT BY MOUTH. THAT DETERIORATING WHEN THE STIMULATION AND THERE WAS PLASTICITY INDUCED OVER TIME. AFTER THE STUDY WAS OVER WE WERE DOING STUDIES AND HIS NAME WAS GREG PEARSON AND I HAVE CONSENT TO SAY HIS NAME AND HE WANTED TO STOP AND IT SPEAKS TO THE NOTION OF REGAINING AGENCY AND RESTORING VOICE. THIS PROJECT HAS HELPED US UNDERSTAND WHAT'S BEEN DESCRIBED AS THE MESOCIRCUIT FROM THE HYPOTHALMUS TO THE CORTEX AND INHIBITS FROM TAKE THE BREAKS OFF THE THALAMUS AND CREATING THIS ACTIVATION FRONTALLY. WE SEE HERE UNRELATED TO OUR STUDY HERE THE FRONTAL CORTEX SHOWED THE MESO CIRCUIT. AND GET TO THE MOTION OF RISK AND THERE'S A REPORT ON RESEARCH ON SUBJECT LACK DECISION-MAKING CAPACITY AND GETTING TO THE EARLIER COMMENTS HAVING A GRADATION NOTION OF MEDICAL RISK. AND I'LL STOP THERE. THANK YOU VERY MUCH. A AAS >> NEXT WE HAVE ANNA WEXLER IN THE TRANSCRANIAL STIMULATION SPACE AND RISK. >> GOOD MORNING. I'M A POST DOCTORAL FELLOW AT THE UNIVERSITY OF PENNSYLVANIA. TODAY I'LL TALK ABOUT TRANSCRANI TRANSCRANI TRANSCRANIAL STIMULATION AND AS A NOD TO THE INVASIVE AND NONINVASIVE DEVICES I HAVE IT IN QUOTATION MARKS. I'LL START BY TELLING YOU ABOUT WHAT TOOK PLACE AT A SUMMIT LAST YEAR IN GERMANY. I ATTENDED AND IT WAS QUITE INTERESTING DISCUSSION AND THERE WAS A PAPER THAT CAME OUT BASED ON THE RESULTS OF THE SUMMIT FOUR MONTHS AGO. I'LL TELL YOU HOW RISK WAS CONCEPTUALIZED IN THE PAPER. NEXT I'LL CONSIDER WHAT RISKS THE SUMMIT AND THE RESULTING PAPER FAILED TO CONSIDER. WHAT THAT DID CONSIDER AND MAYBE WERE THEY COULD HAVE CONSIDERED OTHER THINGS AND I'LL TALK ABOUT RISKS OF TS USE, TRANSCRANIAL ELECTRIC ELECTRICAL STIMULATION AND CORRESPOND TO WHAT HOLLY HAD IN WHAT'S NEXT AND CONSUMER APPLICATIONS AND THE USE OF TDS ON BRAIN WELLNESS CLIPPICS. CLINICS. I'M NOT GOING TO BE TALKING ABOUT ALL KINDS OF NON INVASIVE BRAIN STIMULATION JUST TRANSCRANIAL STIMULATION USING LOW INTENSITY OF CURRENT. TDS IS THE MOST WELL KNOWN AND TACS WHICH USING ALTERNATING AND RANDOM NOISE. THE TECHNIQUE I'M NOT TALKING ABOUT ARE TMS AND ECT. THEY'VE BEEN AROUND LONGER ESPECIALLY ECT AND I THINK THE RISKS ARE MORE WELL DOCUMENTED I'D SAY WHERE TES IS RELATIVELY NEW IN THE LAST TEN YEARS OR SO. SO THE SUMMIT IN GERMANY BROUGHT TOGETHER 40 DIFFERENT RESEARCHERS ON TMS AND THERE WERE PAPERS REGARDING GUIDELINES PREVIOUSLY. THIS WAS INTENDED TO FOLLOW-UP ON WHAT HAD BEEN DONE WITH TMS. I'M FOCUS ON THE ISSUE OF RISK. THIS IS FROM THE RESULTING PAPER AND THEY USE THE MODEL OF THE WORLD HEALTH ORGANIZATION GUIDING PRINCIPLES FOR MEDICAL DEVICES. THEY ACKNOWLEDGE ALL STIMULATION PROTOCOLS CARRY A CERTAIN DEGREE OF RISK. THERE'S NOTHING WITHOUT RISK. NO TRANSCRANIAL ELECTRICAL SYST STIMULATION WITHOUT RISK AND IT COULD RESULT IN SAFETY PROBLEMS AND THE MOST IMPORTANT LINE IT'S A COMBINATION OF THE HAZARD AND THE LIKELIHOOD OF THE OCCURRENCE AND THE SEVERITY. SO RISK SAY PROBABILITY MEASURE WITH THE POTENTIAL SEVERITY OF THE A.E. SO ONCE THAT FRAMEWORK IS IN PLACE, THE NEXT STEP IN THE PAPER WAS TO LOOK AT THE DOCUMENTATION MUCH ALL THE A.E.s IN THE LITERATURE AND HOW CAN THAT WEIGH IN ON OUR NOTION OF RISK. THE PAPER SET THIS OUT ON COMMON TERMINOLOGY CRITERIA FROM GRADE ONE TO FIVE INCREASING IN SEVERITY. MILD AEs ARE SKIN TINGLING AND ONE FOR SKIN BURNS AND SEVERE AND LIFE-THREATENING AE AND DEATH. THE MILD AEs OBSERVED ARE ITCHING, BURNING SENSATION THESE ARE TYPICALLY WHERE THE ELECTRODES ARE PLACED. AND MODERATE AEs ARE LESS COMMON BUT DO EXIST AND THERE'S NOTHING REPORTED GRADE THREE OR HIGHER. BASED ON THIS THE PAPER CONCLUDED LOW INTENSITY TDS IS PRETTY SAFE. AND THERE'S CALCULATING THE RISK BUT I WANT TO FOCUS ON THE RISK OF AEs. I WANT TO SUGGEST AEs FOCUS TENSION ON SHORT-TERM EASILY QUANTIFIABLE EFFECTS AND THINGS TO CONSIDER. LONG-TERM EFFECTS. THESE ARE LONGITUDINAL EFFECTS. THERE'S SEVERAL SESSION STUDIES AND THE LONGITUDE FALL EFFECTS MAY NOT BE MEASURED. WHEN YOU THINK OF DRUGS AND DEVICES EVEN THOSE FDA APPROVED THE MODERATE AEs ARE NOT CALCULATED. WHAT MANUFACTURERS ARE REQUIRED TO REPORT ARE SERIOUS AEs. YOUR MISSING THE LONGITUDINAL EFFECTS OF ADVERSE EVENTS. THE SECOND THING THE FOCUS IS MISSED IS ON THINGS NOT EASILY QUANTIFIABLE. THERE MAY BE MORE SUBTLE EFFECTS ON COGNITION THAT ARE ONLY MEASURABLE IF YOU KNOW WHAT YOU'RE LOOKING FOR AND IF YOU HAVE A STUDY SET OUT MEASURE THAT EFFECT. WE DON'T TEND TO THINK OF THEM AS DIRECTLY AS HEALTH ISSUES. THEY FALL IN ANOTHER CATEGORY BUT THEY'RE SOMETHING TO THINK ABOUT. I WANT TO TALK ABOUT RISK OF TES USE OUTSIDE THE LABORATORY. THIS IS WHAT I FOCUS MOST MY RESEARCH ON IS HOW SCIENCE IS USED OUTSIDE THE LABORATORY. THOUGH WE OFTEN THINK ABOUT SCIENCE AS CONDUCTED ON THE INSIDE OF A LABORATORY, I THINK IT'S IMPORTANT TO RECOGNIZE THAT THE RESEARCH THAT NIH AND OTHER AGENCIES FUND IS BEING USED OUTSIDE THE LABORATORY IN WAYS RESEARCHERS HAVE NOT ALWAYS INTENDED OR BE THAT HAPPY ABOUT. IT'S THE CASE WITH A LOT OF KINDS OF RESEARCH NOW. WE'RE SEEING A PROLIFERATION OF CITIZEN SCIENCE AND DO-IT-YOURSELF MEDICAL MOVEMENTS. I THINK THIS HAS BEEN PARTICULARLY SALIENT IN THE WORLD OF THE NONINVASIVE NEURAL STIMULATION. THERE'S A MOVEMENT THAT AROSE WHERE INDIVIDUALS BEGAN HEARING TDCS MAY HAVE BENEFICIAL EFFECTS FOR ENHANCING COGNITION OR SELF-TREATING A VARIETY OF DISEASES AND DISORDERS. RATHER THAN WAIT FOR THE TECHNOLOGY TO COME TO THEM THEY BEGAN TO BUILD THEIR OWN DEVICES. THEY'RE DOING IT MOSTLY EITHER FOR TREATMENT OF DEPRESSION OR COGNITIVE ENHANCEMENT. IN TERMS OF RISK, I THINK ONE OF THE MAIN ISSUES IS WHILE THEY MAY ADHERE TO THE LEVEL AND STIMULATION SESSIONS USED IN SCIENTIFIC STUD YES THEY'RE STIMULATING LONGER AND MORE FREQUENTLY THAN SCIENTISTS. THERE MAY BE RISK TO THE DEVELOPING BRAIN. IN THE STUDIES THAT EXIST THERE HAVE NOT BEEN ANY MENTION OF USES ON THOSE ON YOUNG CHILDREN THOUGH IN A RECENT STUDY A SMALL NUMBER OF INDIVIDUALS WERE USING IT ON OTHERS. SOMETIMES THEIR CHILDREN. I DID NOT ASK THE AGE SO PROVES STUDIES ONES I DID AND OTHER FOUND THE TYPICAL AGE OF A HOME USER WAS IN THEIR 20s OR 30s. I FOUND A HIGHER MEAN AGE IN THE LATEST STUDY OF 45. THAT WAS QUITE INTERESTING. THERE MAY BE I THINK FOR A SUBSET OF INDIVIDUALS THERE MAY BE AN INDIVIDUAL WITH REGARD TO USING STIMULATION ON OTHER PEOPLE. FINALLY, SOMETHING TALKED A LOT ABOUT IS THE TREATMENT ENHANCEMENT. HOW THE TREATMENT ENHANCEMENT USES RISK CALCULATION. PEOPLE USE IT FOR COGNITIVE ENHANCEMENT AND FOR SELF-TREATMENT. THOUGH I WOULD SAY I ALSO THINK THAT THESE ARE VERY INDIVIDUAL CALCULATIONS AND SUBJECTIVE AND PERSONAL AND THE USER MAKES ON THEIR OWN. NEXT IS ANOTHER APPLICATION OF TDCS DIRECT TO CONSUMER COMMERCIAL APPLICATIONS. SOMETHING HAOLLY BROUGHT UP SHE MENTIONED THE DEVICE CALLED HALO. IT'S HEADPHONES THAT PROVIDE TDCS MARKETED FOR ATHLETIC ENHANCEMENT AND STARTED TO MARKET IT NOW FOR MUSICAL ABILITY ENHANCEMENT OR BEING ABLE TO LEARN FASTER SPECIFICALLY WITH REGARD TO MOTOR SKILLS AND MUSIC ONE IS CALLED THINK. THIS IS MARKETED FOR MOOD ENHANCEMENT. WHAT WE'RE STARTING TO SEE NOW YOU IS ACTUALLY OTHER COMPANIES COMING TO MARKET WITH OTHER PRODUCTS THAT ARE NOT NECESSARILY TDCS THAT USE OTHER TRANSCRANIAL OR TRANSCUTANEOUS STIMULATION ONE EXAMPLE IS NIRVANA THAT LAST YEAR RAISED MILLIONS ON INDIEGOGO AND HAVE THE FIRST VAGAL NERVE STIMULATION PRODUCT OUT THERE. THIS HIT THE MARKET BEFORE FDA APPROVED THE FIRST TBNS DEVICE APPROVED FOR CLUSTER HEADACHES. THIS CONSUMER PRODUCT CAME OUT BEFORE THE FDA APPROVED IT. AND THERE'S NO ENFORCEMENT ACTION IN THE U.S. AND THERE IS RESEARCH ON THESE PRODUCTS GOING ON IN CORPORATE AND COMMERCIAL CONTEXT AND MAY NOT ESTABLISH STIMULATION PROTOCOL. THE PROTOCOL MAY BE DIFFERENT THAN WHAT'S USED IN A LABORATORY. ANOTHER INTERESTING EXAMPLE IS THE WAY IT'S BEING USED OUTSIDE THE LABORATORY IS IN BRAIN WELLNESS CLINICS. WE'RE SEEING A PROLIFERATION OF THE CLINICS. I HAVE A STUDY THAT LOOKS AT THE USE IN THE CLINICS. THIS IS VERY INTERESTING. IT'S COMMONLY THOUGHT TDCS IS USED OFF LABEL. MY QUESTION IS ARE THESE INDIVIDUALS -- HOW CAN THE USE BE OFF LABEL. WHAT IS PRESUMED IS INDIVIDUALS WERE USING DEVICES FDA CLEARED AND MODIFYING THEM FOR TDCS USE. I FOUND THIS WAS NOT WHAT WAS HAPPENING. THE INDIVIDUAL OR PRACTITIONERS WERE USING DIRECT-TO-CONSUMER DEVICES AND I THINK ONLY A THIRD WERE USING THEM. MANY ARE USING DIRECT TO CONSUMER DEVICES. AN ABOUT NUMBER OF THEM DON'T HAVE MEDICAL OR SCIENTIFIC DEGREES. SOME HAVE DEGREES IN MUSIC THERAPY. MANY ARE MISINFORMED ABOUT THE STATUS OF TDCS. PART OF WHY THEY CAN DO IT IS AT STATE LEVEL THE REGULATIONS THAT GOVERN VARY. THE CERTIFICATIONS TO PRESCRIBE DRUGS AND WHO CAN USE THE DEVICES IS UNREGULATED OR UNDEFINED. IT'S LOOSE AND YOU CAN SET UP SHOP AND ADMINISTER TO SOMEONE ELSE. IT'S INTERESTING AND HAS NOT BEEN WELL STUD YESTERDAY. -- STUDIED. I WANT IT MAKE THE ONE POINT WHEN YOU TALK ABOUT RISK AND RISK ASSESSMENT. WE OFTEN FOCUS ON A DEVICE OR PROTOCOL IS IT SAFE OR RISKY. IT'S IMPORTANT TO CONSIDER. IT'S HOW PEOPLE USE IT. WE CALL IT MISUSE OF A DEVICE OR PROTOCOL BUT WE HAVE TO THINK ABOUT THE ISSUE OF USE MORE BROADLY WHEN WE THINK ABOUT RISK. THAT'S IT. THANK YOU VERY MUCH. SO I WOULD LIKE THE PANELISTS TO COME UP AND SIT AT THE FRONT AND WE HAVE -- WE'RE SUPPOSED TO GO TO 12:10. WE CAN MAYBE GO A LITTLE LONGER AND SEE HOW IT GOES. >> Question: ON NONINVASIVE THERE'S MANY OVERLAPPING AUTHORITIES. WE FOCUS ON MEDICAL DEVICES THAT MAY CHANGE THE STRUCTURE OR FUNCTION OF THE BODY. IF IT CHANGES THE STRUCTURE OR FUNCTION OF THE BODY IT MAY DEPEND UPON WHAT WE KNOW ABOUT THE PRODUCT. EVEN IN THE ABSENCE OF A CLAIM IT MAY BE REGULATED AND MAY BE UNDER OUR JURISDICTION. EVEN IF YOU HAVE CLAIMS THAT IT'S NOT A MEDICAL DEVICE AND SAY IT'S SAFE THERE IS STILL A RISK WITH THE STIMULATION. THE BEST WAY TO KNOW IF YOU FALL OUTSIDE OUR AUTHORITY IS PRESUBMISSION. WE HAD A WORKSHOP. IT WASN'T THE JAZZIEST MEETING. THE FDA DOESN'T THROW JAZZY MEETINGS BUT WE TRIED TO GET THE WORD OUT. RISK CAME UP IN THE PREVIOUS SESSION. MEDICAL DEVICES ARE CLASSIFIED BY RISK, CLASS 1, 2 AND 3. WE DEFINE RISK AS POSING A CONCERN TO THE PATIENT AS HEALTH, SAFETY OR WELL BEING OF THAT INDIVIDUAL. SAFETY TOOLS ARE IMPORTANT. WE HAVE A NUMBER OF TOOLS AND CONSENT DOCUMENTS, RULES, EVALUATION COMMITTEES, STAGGERED ENROLL MANY, STAGED ENROLLMENT. THERE'S A NUMBER OF TOOLS. MY QUESTION TO THE GROUP FOR MAYBE THINKING ABOUT RECOMMEND S GOING FORWARD, HOW CAN WE GET THE BEST PRACTICES FOR INVASIVE AND NONINVASIVE DEVICES TO THE INVESTIGATORS ENTERING THIS FIELD. IF THEY KNOW SOME OF THE TOOLS ON HOW TO ENSURE OR MITIGATE RISK THAT WOULD BE A VERY GOOD THING TO THE COMMUNITY. THE THIRD POINT IS WHY DO YOU SAY MEDICAL DEVICES ARE UNREGULATED. I WALKED TRUE -- THROUGH THE QUESTIONS WE ASKED. ON THE PREVIOUS SLIDES WHY DO YOU IDENTIFY IT AS AN UNREGULATED SPACE. I'D BE HAPPY TO KNOW. >> I SAID IT'S BEEN NO REGULATORY ENFORCEMENT ACTION TAKEN. THERE HAS BEEN NO PUBLIC REGULATORY ENFORCEMENT ACTION TAKEN. TO ANYONE'S KNOWLEDGE THERE'S BEEN NO ACTION TAKEN AND LET ME JUST RESPOND MORE I'VE ARGUED IN A PAPER THESE DEVICES ARE REGULATED BY A NUMBER OF AGENCIES AND THERE IS NO REGULATORY GAP AND TO CALL THEM UNREGULATED IS WRONG. I CLEARLY ARGUE THAT IN A PAPER I HAVE AND THE MORE PUBLIC REGULATORY ENFORCEMENT AND I THINK AT THE MOMENT IT'S UNCLEAR WHO JURISDICTION THESE DEVICES ARE FALLING UNDER OR WHO WILL TAKE THE LEAD OR MAYBE THERE COULD BE INTERAGENCY COLLABORATION IS UNCLEAR BUT I AGREE WITH EVERYTHING ELSE YOU SAID. [RESPONSE OFF-MIC] >> Question: THERE'S CHECKS AND BALANCES BUT PEOPLE NEED TO BE CAREFUL THAT'S UNREGULATED OR NO ACTIONS BEING TAKEN. THEY'RE TALKING ABOUT EVENTS OR ACTIONS THEY DON'T HAVE DATA FOR. IT'S INTERESTING TO HAVE THE DEBATE WHEN THERE'S OTHER INFORMATION AT PLAY. >> I APPRECIATE ALL THE TOOLS AND SAFEGUARDS THAT YOU HAVE. WHAT I WANT TO PUSH THOUGH THAT WE NEED THE RIGHT SAFEGUARDS FOR THE RIGHT PEOPLE NOT MORE SAFEGUARD. WE ALSO WANT TO MAKE SURE WE DON'T IN AN ATTEMPT TO SAFEGUARD THE POPULATIONS TO DISCRIMINATE AGAINST POPULATIONS LIKE JOE TALKED ABOUT. WE NEED TO ALWAYS BE ATTENTIVE WHEN I TALK TO CLINICAL RESEARCHERS THAT'S NOT MORE, IT'S THE RIGHT ONES, THE EFFECTIVE ONES TO SUPPORT OUR SUBJECTS PATIENT, PARTICIPANTS WHOEVER THEY ARE IN THE BEST SAFEST AND MOST RESPECTFUL ARGUMENTS. >> YOU >> Question: YOU WANT TO INVOLVE THAT INFORMATION IN THE STUDY YOU'RE INVOLVED WITH. AGREE. >> HANNAH AND WINSTON. >> THANK YOU. >> IS THERE MACHADO STILL ON THE CALL . >> I HAVE A QUESTION TO FOLLOW BUT I CAN WAIT FOR THE OTHERS TO ASK THEIR QUESTIONS AND IF YOU GIVE ME A CHANCE I'LL ASK MINE. >> IT'S GOOD TO KNOW YOU'RE STILL THERE BECAUSE MY QUESTION RELATES TO SOMETHING YOU RAISED AND OTHER PANELISTS RAISED. I WANTED TO ASK ABOUT RISKS RELATING TO PERSONALITY CHANGES PARTICULARLY IN THE CONTEXT OF DEEP BRAIN STIMULATION AND HOW YOU THINK THE PERSONALITY CHANGES SHOULD BE CONCEPTUALIZED AND MEASURED WHEN OFTEN THE POTENTIAL APPLICATIONS OF DEEP BRAIN STIMULATION MAY BE TO EFFECT THINGS THAT ARE CLOSELY RELATED TO PERSONALITY OR PARTLY C CONSTITUATIVE AND I WANTED TO HEAR MORE FROM THE EXPERTS IN WHAT THEY THINK OF RISKS IN PERSONALITY CHANGES AND HOW TO THINK ABOUT THOSE WITH DBS PARTICULARLY IN PSYCHIATRIC POPULATION. >> ONE OF THE RECENT NIH RO1s WENT TO A CLINIC WARE WE'RE CLAB WE'RE COLLABORATING ON THIS AND IT'S IMPORTANT TO FRAME IT ON PERSONALITY CHANGE BECAUSE WE ALL HAVE MILD CHANGES IN OURSELVES BUT PERSONALITY CHANGES THAT MATTER TO PATIENTS AND THEIR LIVES. IT'S INCREDIBLY COMPLEX NOT JUST CHANGE IN A NEUROPSYCHIATRIC DOMAIN AND MEANINGFUL POSITIVELY OR NEGATIVELY TO A PATIENT POPULATION. THIS IS CURRENTLY BEING STUDIED WITH METRICS AND IT'S TRAITS AND ALL FRAMED IN HOW WE BRING OURSELVES TO AN UNDERSTANDING. >> IF I CAN FOLLOW WITH THE PRESENTATION TODAY. THE QUESTION OF PERSONALITY CHANGE IS AN INTERESTING ACADEMIC QUESTION. IN DOING THE WORK I DO WHICH IS ROUTINE IMPLANTATION OF DEVICES FOR MOVEMENT DISORDERS AND PARTICIPATING IN MANY CLINICAL TRIALS, I HAVE YESTERAY TO SEE A PERSONALITY CHANGE TO A CLINICAL CONCERN. SHOULD WE INVESTIGATE IT? WE SHOULD. I THINK IT'S A CONCERN FOR SOME PATIENT AND FAMILIES. I WOULD LIKE THE TREATMENT OF PSYCHIATRIC DISORDERS SUCH AS MOOD DISORDER TO THE MANIPULATION OF A PERSON'S PENALTY BECAUSE I DON'T THINK IT'S TRUE. AND WE NEED TO EVALUATE FOR POSSIBLE OR QUESTIONABLE CHANGE IN PERSONALITY. EVEN IF WE FIND THERE ARE NONE WE SHOULDN'T GO INTO THE ETCHTENT EXTENT OF BECAUSE WE ARE DOING SURGERY IN THE BRIN OR TREATING A PSYCHIATRIC DISORDER THE INTENT IS TO MODIFY ONE'S PERSONALITY OR THE LIKELIHOOD BECAUSE IT'S NOT THE CASE. . >> I THINK THERE'S A PERVASIVE THEME OF THE DAY THROUGH THE USE OF WORDS AND WHAT THEY MEAN AND NOT BEING A PHILOSOPHER BUT BEING A NEUROLOGIST IT'S ON DATA AND OBJECTIFYING WHAT YOU THINK YOU'RE SAYING. WHEN WE USE THE TERM AND I LOVE PAUL'S DEFINITION WITH INVASIVE AND WHAT WE THINK WHAT WE MEAN AND THE DEPRESSION SPHERE WHICH IS IT THE ONLY THING WE NO ABOUT, IT'S CLEAR WATCHING OVER MANY YEARS THE PATIENTS THAT WE IMPLANT. WHEN WE MEET THEM THEY ARE IN STATE A, DEPRESSED, CAN'T MOVE, I HAVE NO IDEA WHAT THEIR PERSONALITY IS. THE PERSONALITY PSYCHOLOGISTS SAY YOUR PERSONALITY IS HARD WIRED AND HAVE WAYS THE THINK THEY MEASURE IT THAT RELY ON SELF-REPORT AND DO YOU CHANGE IT? A PATIENT'S PERCEPTION WITH THEIR BRAIN IN STATE A IS DIFFERENT THAN IN STATE B. AND WE ARE DEPENDENT ON GETTING THEM TO TELL US WHERE THEY ARE AND WE THINK WE ARE QUANTIFYING SOMETHING. WE ARE DELUSIONAL. WHAT WE DO KNOW IS THAT PEOPLE MOVE BETWEEN STATES AND DEVELOP AGENCY AS JOE TALKED ABOUT. I THINK DEPRESSED PATIENTS DEVELOP AN AGENCY ON WHERE THEY ARE RELATIVE TO WHERE THEY USED TO BE AND NO ONE IS EVER THE SAME AS WHERE THEY STORED IT. SO TALKING ABOUT CHANGING PERSONALITY. WE CHANGE STATES WITH THESE IMPLANTS. WHAT I NOTICED LIKE ANDRE SAID ABOUT WHAT HE THINK ABOUT HIS EXPERIENCE WITH HIS PATIENTS. IN OUR TARGET WE TAKE AWAY SOMETHING AND THEN WE ACTUALLY MEET PEOPLE. WE MEET PEOPLE WE DIDN'T KNOW WITH VARIOUS PERSONALITY AND HOW THEY RESPOND IS THE ISSUE. THAT'S IN OUR TARGET. IT'S VERY CLEAR IN OUR TARGETS AND WHAT I LEARNED FROM SARAH I THINK THERE'S FUNDAMENTALLY A DIFFERENT WAY IN WHICH PEOPLE'S PERCEPTION OF THEIR CURRENT STATE IS DIFFERENT IN BEING STIMULATED IN DIFFERENT TARGETS. THAT GOES TO BIOLOGY AND IT'S NOT THE SAME IN ALL. THE PERCEPTION WILL BE DIFFERENT AND THE BIOLOGY WILL BE DIFFERENT AND YOU CAN MEET A PERSON AND THE PLASTICITY IS IN A DIFFERENT LOCATION. IN WHAT IS PERSONALITY WE HAVE TO KNOW WHO THEY ARE BEFORE WE MEET THEM AND THAT'S HARD FOR SURGEONS AND RESISTANT PATIENTS WHERE WE HAVE NO HISTORY AND THAT'S THE SCOURGE OF THE STUDIES. IT'S NOT FIXING A BROKEN ARM AND THEN I CAN MEASURE IF THE BONE IS SET OR NOT, YES OR NO. HERE'S MY X-RAY. WE HAVE TO DEFINE WHAT WE DO IN DIFFERENT TARGETS. THE PERSONALITY THING IS A PANDORA'S BOX AND WE HAVE TO DECIDE WHAT WE'RE SAYING. A PSYCHOLOGIST WILL SAY PERSONALITY IS PERSONALITY AND THAT'S NOT TRUE EITHER. >> I AGREE WITH ANDRE AND WITH WORK ON DEPRESSION THE PEOPLES AS THEY HAVE THEIR DEPRESSION TREATED REFER BACK TO THEIR FORMER SELVES AND IT'S THE STANCE ABOUT THE NEW SELF. IT'S THE CONTINUITY. WE'VE SEEN THIS IN THE PERSONALITY OF PEOPLE WITH BRAIN TECHNOLOGY AND AS ONE PERSON RECOVERED HIS NEW SELF HE WAS STILL LIKE HIM AND THEY CAN HELP US UNDERSTAND IT CONTINUITIES AND GIVE US A RELATIONAL BIOMARKER WHAT THE OBJECTIVE PERSON SHOULD BECOME MOVING TOWARDS A RECOVERY AND HEALING. >> YOU UNMASK THE PATHOLOGY OF FAMILIES. YOU THINK -- AND I'D LIKE TO THINK WHEN SOMEONE HAS A DEVASTATING HEAD INJURY FAMILIES ON BOARD TO SEE THE PERSON COME BACK -- [NO AUDIO] -- IT COMES OUT OF WHAT PEOPLE GET BETTER AND YOUR RELATIONSHIP WITH YOUR LOVED ONE THAT IS IMPAIRED IT'S ALL COMPLICATED. THIS IS WHAT PSYCHIATRISTS DO FOR A LIVING. IT'S NOT WHAT WE DO FOR A LIVING IN THE SPACE BUT HAVE TO BE AWARE OF IT. YOU THINK YOU'RE RETURNING SOMEONE TO A FAMILY UNIT AND YOU SEE THE FAMILY IS NOW FREE TO BOLT. >> WE SHOULDN'T RECAPITULATE WHERE WE LOOK AT AUTONOMY AND ISOLATION AND EVERYTHING GOING AROUND HIM OR HER BECAUSE THE AGENTS THAT ARE REEMERGING ARE REEMERGING IN THE MORE COMPLEX SYSTEM. >> AND SOMETIMES I MEET WITH POTENTIAL SUBJECTS TO HIGHLIGHT WHAT IN THEIR LIFE THIS IS LIKELY TO CHANGE AND MAKE BETTER. >> THERE'S CHANGES THAT OCCUR WITH CHANGES IN PARKINSON'S WHERE THE FAMILY STRUCTURE CHANGES. THIS IS WELL KNOWN. IS THAT A PERSONALITY CHANGE. MAYBE. IS IT A BAD THING OR GOOD THING. THE QUESTION IS WHAT IS THE NUGGET IS THE INDIVIDUAL HAPPY WITH THEIR THERAPY. MAYBE IT WAS A COUNTERPRODUCTIVE RELATIONSHIP AND ARE WE YOU MENTIONED WARE FOCUSSED ON THE DEVICES. IS THERE A PARALLEL DISCUSSION REGARDING WHAT ARE DRUGS DOING IN PSYCHIATRIC DISEASE. >> I'D LIKE TO TALK ABOUT INVASIVENESS AND NONINVASIVENESS AND WHAT MATTERS. WE SEE CHANGES AS IN PARKINSON'S AND DO WE SEE CHANGES IN DYNAMICS WHEN A PERSON DOESN'T NEED AS MUCH HELP OR DOING ACTIVITIES OF DAILY LIVING. DID WE CHANGE SOMEONE'S PERSONALITY OR IS IT MORE LIKELY I WANT TO THANK THE POINTS MADE THAT BEFORE WE GO MAKE ASSUMPTIONS ON WHETHER THE EFFECT WE'RE SEEING AMOUNT OR NOT WITH CHANGE IN PERSONALITY BEGIN TO LEARN WHAT IS IT WE'RE MEASURING AND THE CONFOUNDS ASSOCIATED WITH THE THINGS WE'RE MEASURING INCLUDING SOCIAL AND ECONOMICAL CONFOUNDS. ON THE SECOND PART ON MEDICATION VERSUS INVASIVE TREATMENTS LIKE BRAIN STIMULATION WE HAVE AN INTERESTING THEME ONCE WE TAKE OUT THE RISK SO THE RISK OF MAKING A HOLE IN THE HEAD AND IMPLANTING A SYSTEM IN THE BRAIN DO WHAT DO WE CHANGE THE RISK RELATED TO SOMETHING THAT PENETRATES THE BRAIN OR SYSTEMICALLY DELIBERATE VERY -- VIA A PILL OR APPLIED TOPICALLY TO THE SKIN TO GO TO THE BRAIN. ONCE WE TAKE OUT THE RISK SHOULD WE LOOK AT RISK OF THERAPY OVERALL REGARDLESS OF THE FORM OF DELIVERY THROUGH THE BLOOD STREAM OR AN ELECTRODE INSIDE THE BRAIN OR OUTSIDE THE HEAD. >> TO YOUR POINT, IS A MIR. WE SHOULD BE LOOKING AT THE DRUGS AND MEDICAL DEVICES IT SEEMS THERE'S SOMETHING ABOUT ELECTRICAL BRAIN STIMULATION THAT MAKES PEOPLE THINK A BIT MORE ABOUT IT BUT THEY'RE APPLICABLE IN THE SAME WAY TO DRUGS. >> AND THERE'S DISSIMILAR FEELINGS IF YOU DIDN'T LABEL THEM AT SUCH WITH THE RIFT -- HISTORY WE WOULDN'T HAVE THE SAME FACTOR. THAT'S HOW I GOT MY FOOT IN THE DOOR. I WANTED TO ASK A CONCRETE QUESTION TO JOE AND HOW WE GET THE STUDY APPROVED. THE FIRST INTERVENTIONAL STUDY. I SUPPOSE I SHOULD KNOW WHAT HAPPENED BUT I DON'T. YOU SAID PHASE 1 WOULD BE DISINGENOUS AND WE ALWAYS HOPE FOR A THERAPEUTIC EFFECT. HOW DID IT GET APPROVED. UNDER WHAT RISK CATEGORY DID YOUR IRB SAY DID THEY SAY THIS WAS PROSPECT FOR DIRECT BENEFIT? THEY DIDN'T. THEY SAID IT'S NON THERAPEUTIC AND ON A SURROGATE BASED BUT THOUGHT IT WASN'T MORE THAN MINOR INCREASE OVER MINIMAL RISK. >> WE WERE IN A STATE OF EQUIPOISE AND DIDN'T SAY IT WAS DESIGNED TO BE THERAPEUTIC. WE WERE STILL IN THE STATE OF EQUIPOISE. >> HOW CAN YOU HAVE CLINICAL EQUIPOISE WHEN YOU'VE DECIDED IT DOESN'T HAVE THERAPEUTIC INTENT? >> ONE OF THE CHALLENGES AND THIS IS A REALLY IMPORTANT POINT ABOUT INVESTORS WHO DO THIS WORK FOR A LONG PERIOD OF TIME WOULD NOT BE DOING IT IF THEY DID NOT THINK IT WAS GOING TO BE THERAPEUTIC. >> WHICH IS MY POINT. >> BUT THAT'S DIFFERENT THAN KNOWING IT'S GOING TO BE THERAPEUTIC AND HAVING THE CERTAINTY THAT ALLOWS YOU IN THE CONSE CONSENT PROCESS GIVEN THE POWER DYNAMICS TO ENGAGE AND IMPLY. YOU ARE HOPING IT'S THERAPEUTIC BUT HAVE TO BE JUDICIOUS IN NOT SAYING IT IS. >> LET'S PUT ASIDE THE EQUIPOISE QUESTION. HOW DID THE IRB CATEGORIZE NON-THERAPEUTIC RESEARCH AS IT RISK LEVEL WHATEVER IT WAS THEY SAID THAT WAS CONSISTENT WITH THE REGULATIONS WITH SURROGATE LAR RESEARCH. >> THE OTHER CAVEAT THAT'S IMPORTANT IS THE RISK UNDERSTOOD TO BE COMPARABLE TO THE RISK FOR APPROVED INTERVENTIONS FOR PARKINSON'S DISEASE, DEEP NUCLEI AND ESTABLISH THERAPY. SO IT WAS A NEW APPLICATION BUT THERE WAS A TRACK RATE OF 40,000 TO 50,000 PEOPLE AND MORE NOW HAVE GOTTEN IT FOR PARKINSON'S DISEASE. THE RISKS WERE KNOWN FOR THIS INTERVENTION FOR A DIFFERENT TARGET IN A DIFFERENT POPULATION. >> CHRISTINE, DID YOU HAVE A COMMENT? >> IT'S GETTING TO A DIFFERENT LEVEL OF PRACTICALITY ACTUALLY. I THINK ONE OF THE QUESTIONS -- I THINK THERE'S BEEN A LOT OF REALLY GREAT DISCUSSION ABOUT HOW DO WE DESCRIBE RISKS, WHAT ARE RISKS, IT'S MORE THAN JUST THE AEs ON THE CTC, FOR EXAMPLE. I THINK WHAT WE NEED TO TALK ABOUT IS WHY DO WE CARE ABOUT RISK. WE TALK ABOUT LONG-TERM RISKS. MAYBE WE NEED PUBLIC EDUCATION TO THE WELLNESS CLINICS OR THE PEOPLE WHO USE WELLNESS CLINICS DON'T -- AREN'T MISINFORMED OR MISLED. I'D LOVE TO HEAR MORE -- WHY DO WE CARE? WHY DO WE WANT TO CATEGORIZE THE RISKS AND WHAT DO WE USE THE CAT CATEGORIZATIONS FOR. >> I'M BIG IN THE TRUTH IN ADVERTISING IN A LOT OF DIFFERENT KINDS OF DOMAINS. SO IN THE CLINICAL ENVIRONMENT I'M IN, THESE RESEARCH PROJECT THEN GET TRANSLATED INTO CLEAR EXPLANATIONS TO PATIENTS SO THEY AND THEIR SURROGATES SO THEY CAN JUDGE WHETHER THIS IS SOMETHING THEY WANT TO UNDERTAKE. IT ALSO INFORMS MY CLINICIAN COLLEAGUES ON THEIR LIMIT OF THEIR CONSCIOUS THEY'RE WILLING TO EVEN OFFER. IF I KNOW LONG-TERM REPEATED EXPOSURE TO MAGNETIC STIMULATIONS LONG TERM MY COLLEAGUES MAY SAY I CAN'T IN GOOD CONSCIENCE RECOMMEND THIS TO MY PATIENT BUT THEY NEED TO KNOW YOU'RE TRADING NEAR TERM BENEFIT FOR LONG TERM HARM. IN THE END THIS IS WHERE THE RUBBER MEETS THE ROAD. THIS IS A TRANSPARENCY SO PEOPLE CAN MAKE THE DECISIONS TO TRADE OFF. >> I THINK WINSTON'S BEEN WAITING. >> THE TITLE OF YOUR TALK WAS INVASIVENESS IS THE INVASIVE, NONINVASIVE CAN'T DO ALL THE WORK PEOPLE SUPPOSE. AMONG OTHER THINGS IT'S PROBABLY NOT A GOOD PROXY FOR WHAT'S THE RISK OF AN INTERVENTION LIKE ECT I REGARD AS A HIGH-RISK INTERVENTION THOUGH IT'S NON INVASIVE. A SECOND READING WE SHOULDN'T MAKE A DISTINCTION BETWEEN INVASIVE AND NONINVASIVE. THAT I WOULD DISPUTE BECAUSE I THINK THERE'S ETHICALLY RELEVANT DIFFERENCES BETWEEN INVASIVE AND NONINVASIVE METHODS. ONE HAS TO DO WITH THE CLINICAL CONTEXT OF INVASIVE ELECTROPHYSIOLOGY. WE HAVE WRITTEN A PAPER ON INTRACRANIAL PHYSIOLOGY. THE FACT THEY'RE PATIENTS WITH BRAIN TUMORS AND PARKINSON'S DISEASE CREATES ETHICAL CHALLENG CHALLENGES WHEN NEUROSCIENCE IS BEING RAISED. AND THERE'S DIFFERENT CATEGORIES OF PHYSIO LOGICAL RISK AND IF SOMEBODY'S ALREADY HAVING A CRANIOTOMY OR A BURR HOLE THERE'S THE TENDENCY WE CAN COVER THE ELECTRODE OR EXPAND THE COVERAGE. THERE'S TEMPTATIONS THAT ARISE THAT MAY NOT ARISE IN THE SAME WY OR AT THE LEAST THE FACT THERE'S A DISTINCTION BETWEEN NONINVASIVE AND INVASIVE EVEN IF THERE'S BOUNDARY CASES. IT MEANS THERE'S SOMETHING DIFFERENT. WHEN WE HAVE A SLIPPERY SLOPE AND HAVE DISCONTINUATION JUNCTION AND THAT WOULD BE PENETRATING THE DURA. THERE IS SOMETHING THAT'S SIGNIFICANT. ONCE WE GET PAST THAT THRESHOLD THERE'S AN OPPORTUNITY TO ADD ANOTHER EHECK -- ELECTRODE THAT'S WHY THE INVASIVE, NONINVASIVE MAY KEY US TO ETHICALLY IMPORTANT ISSUES EVEN IF WE DON'T THINK THAT IS THE PRIMARY DISTINCTION BETWEEN WHAT IS RISK AND NOT RISKY. >> I'M NOT CONVINCED BY YOUR ARGUMENT BUT YOU RAISE A NUMBER OF IMPORTANT FURTHER AXES TO TALK ABOUT. THERE'S SURGICAL RISKS AMONG THESE. YOU THINK ABOUT YOU THINK ABOUT THE USE OF ICT AND ANESTHESIA RISK. IT'S ALSO GIVEN FOR THINGS LIKE ECTs. I AGAIN WANT TO STRATIFY IT BY THE KINDS OF RISKS. YOU THINK OF THE NON NONINVASIVE SURGICAL ATTEMPTS BY HIGH FREQUENCY ULTRA SOUND THAT IS DAMAGING OR FOR TRANSCRANIAL STIMULATION. I ALSO WANT IT STUDY THE RISKS. I WANT TO GO BY RISK NOT IDEOLOGICAL DIFFERENCE. >> ANNA AND HANK. THE DEVICES THAT ARE SOLD TO CONSUMERS OR CAUSING HARM TO INDIVIDUALS IS THERE ROOM TO REGULATE THE DEVICES AT A FEDERAL LEVEL FROM DIFFERENT AGENCIES. THEN I THINK ABOUT THE BRAIN WELLNESS CLINICS IF THE PROCEDURES ARE HARMFUL TO SUBJECTS, FIRST, IS THERE A WAY TO REGULATE THAT. THERE MAY OR MAY NOT BE BUT ARE PATIENTS OR CLIENTS BEING WELL ENOUGH INFORMED ABOUT THE RISK. >> I WOULD ADD TO THE INVASIVE, NONINVASIVE. I'M AND YOUR SIDE, PAUL FROM A RISK PERSPECIVE BEING OVERLAPPING CURVES. THERE'S OTHER DIMENSION LIKE ACCESSIBILITY. NO ONE WILL DO DO-IT-YOURSELF BRAIN SURGERY. SO IT'S INVASIVE AND NONINVASIVE FOR THE REASONS OF THE SOCIAL EFFECTS AND ROLL OUTS. THAT TO ME IS MOST IMPORTANT BETWEEN INVASIVE AND NONINVASIVE. >> I'M THINKING MAYBE -- HOW MUCH LONGER DO YOU WANT TO GO? WE WANTED TO HAVE LUNCH TEN MINUTES AGO. HOW HOUUNGRY ARE PEOPLE? KAREN'S BEEN WAITING AND I THINK ANDRE WANTED TO ASK A QUESTION AND I SEE MULTIPLE QUESTIONS IN THE BACK. THE MICROPHONE IS A POINT OF PRIVILEGE. >> THERE'S A WAY TO LOOK AT RISK AND HOW WE STRUCTURE RESEARCH AND CLINICAL CARE. YOU CAN TALK ABOUT RISK AND BENEFIT AND THEY SAY WE'LL FOLLOW ON ON THIS AND FROM A SURGEON'S PERSPECTIVE WE SAY A COMPLICATION EVEN DOWN THE ROAD WHERE I'M KIND OF ATTACHED TO YOU. THE DIFFERENT AS RESEARCHERS WE ASK A PARTICULAR QUESTION AND WHEN IT'S DONE THERE'S A QUESTION OF WELL, WHAT HAPPENS AFTER THE QUESTION'S BEEN ANSWERED AND WHO DO I BELONG TO AND WHO AM I ATTACHED TO AND IT'S DIFFERENT THAN THE CLINICAL ENCOUNTER. EVEN PATIENT'S PERCEPTIONS OF RISK CHANGE BASED ON THE RELATION WITH THOSE CONSENTING. I DON'T THINK WE IDENTIFIED SO MUCH WITH RISK PROFILES BECAUSE WE SAY THESE ARE THINGS IN RELATION TO THE QUESTION WE'RE ASKING BUT PATIENTS DON'T NECESSARILY SEE IT THAT WAY. THAT DYNAMIC ISN'T NECESSARILY REFLECTED IN THE CONSENT PROCESS. IT PLAYS OUT TREMENDOUSLY IN TRUST ISSUES AND POST TRIALS WHICH WE'LL GET TO. THAT'S ANOTHER WAY TO LOOK AT RISK. >> I WANT TO GO TO KAREN BECAUSE SHE'S BEEN WAITING. >> SO THIS IS FOR YOU, PAUL AND ANNA. I WANT TO A DISCUSSION THAT CAME UP EARLIER ABOUT MOVING TOWARDS NON PHYSICAL ARM AND THOSE AROUND PRIVACY AND AROUND LEGACY USE OF DATA WHICH I DON'T THINK HAS BEEN BROUGHT UP YET. I THINK IT'S BECAUSE WE'VE HAD THE FOCUS ON BRAIN STIMULATION RATHER THAN RECORDING. AS I LOOK THROUGH FUNDED GRANTS SOME ARE RECORDING THINGS LIKE DECODING SPEECH PATTERNS, TRYING TO DECIPHER DECISION MAKING. I THINK WHILE THERE ARE SOME ISSUES RELATED TO THINGS LIKE PRIVACY AND LEGACY USE COMMON TO OTHER TECHNOLOGIES. AND IT'S A PROLIFERATION OF PUBLIC/PRIVATE PARTNERSHIPS WHERE UNIVERSITIES MAY WANT TO USE THESE HUGE BANKS IN DATA IF THEY'RE ALLOWED TO IN PARTNERSHIPS WITH COMPANIES. I'LL LEAVE IT AT THAT. >> THE CURRENT APPROVED DEVICE FOR EPILEPSY, ALL THE DATA FOR THE PATIENTS IS DOWNLOADED MOO THE CORPORATE DATABASE AND SERVERS AND WE HAVE RESPONSIVE NEUROSTIMULATION OR CONSTANT BRAIN WAVE PATTERN MEASURING THERE'S PRIVACY THINGS WE WANT TO KEEP IN MIND AS RISK. >> I THINK THE DIRECT TO CONSUMER DEVICES ARE PARTICULARLY INTERESTING. I KNOW THERE'S PEOPLE WORKING ON THE ISSUES. TO MY KNOWLEDGE THE PRIVACY AND WHAT THEY'RE DOING -- THE COMPANIES THAT SELL THE DEVICES WHAT THEY'RE DOING WITH THEY'RE DATA ISN'T TOTALLY CLEAR AND WHETHER THEY SELL IT TO THIRD PARTIES DOWN THE LINE ISN'T TOTALLY CLEAR. IT SEEMS TO BE AN ISSUE WITH THE DEVICES AND OTHER APPS THAT MARKET THEMSELVES FOR HEALTH PURPOSE. THERE'S NO REAL DATA RESTRICTIONS ON THEM AND THESE THINGS AREN'T CLEAR TO PEOPLE WHO ARE USING THESE DEVICES. I THINK IT'S A BIG ISSUE THAT HASN'T BEEN LOOKED AT WELL. >> AND THERE'S A NERVE DIVERSITY DEVELOPMENT AND FUNDED GRANTS IN RECORDING WITH AUTISM AND TRYING TO BETTER UNDERSTAND AUTISM AND SOMEONE WHO IDENTIFIES WITH AUTISM IS HAPPY TO PARTICIPATE BUT DOESN'T WANT THEIR DATA USED IN THE STUDY AND THAT'S ANOTHER RISK. >> WE'LL LET CARLOS MAKE ONE POINT BECAUSE I SUSPECT HE WANT TO CLARIFY AND THEN WE'LL HAVE TO STOP BECAUSE WE'RE OVER BY A DECENT MARGIN. SORRY. >> MEDICAL DEVICES FOR PREVENTION OR THERAPEUTIC THEY BE CLASSIFIED ON 1, 2 OR 3 ON RISK. FOR MOBILE APPS IF THEY'RE TARGETING MENTAL ACUTE OR HELPING YOU STAY AWAKE THOSE ARE CONSIDERED GENERAL WELLNESS PRODUCT. WE DON'T GET INVOLVED IN THAT AREA. THEY PURPORT TO SAY WE'LL DIAGNOSE EPILEPSY OR DIAGNOSE YOUR PARKINSON'S DISEASE WITH WE HAVE QUESTIONS FOR THOSE TYPES OF APPS. THERE'S REGULATION AVAILABLE FOR DIAGNOSTIC DEVICES BUT TO SAY THERE'S NO REGULATION YOU HAVE TO DRILL DOWN TO THE IFU AND PATIENT POPULATION AND INDICATIONS FOR USE AND PRIOR TECHNOLOGIES. THERE'S A LOT OF THINGS THAT GO INTO ASSESSING THE REGULATORY OVERSIGHT FOR A PARTICULAR PRODUCT. IT'S A DISCUSSION THAT I WOULD HOPE IS BROUGHT TO THAT DETAIL AS WE THINK ABOUT BEST PRACTICES FOR NEUROETHICS IN THIS AREA. >> OKAY. I THINK WE'RE GOING TO STOP THERE. SO PLEASE JOIN ME IN THANKING THE PANEL. >> JUST A COUPLE THINGS. THOSE WHO ORDERED LUNCH THROUGH VIVIAN, SHE WILL MEET YOU IN THE BACK AND HAS IT IN THE BACK. IT'S A GREAT OPPORTUNITY FOR ME TO THANK VIVIAN FOR ALL HER HELP IN ORGANIZING THE CONFERENCE AND SARAH FOR ALL THE HELP. I WILL TELL YOU THE WISDOM OF THE PEOPLE WHO WROTE THE REGULATIONS -- I WENT GO THROUGH EACH BUT SO YOU CAN SEE VISIBLY THE KIND OF THINGS WE THINK ARE IMPORTANT FOR INFORMED CONSENT. THERE ARE EIGHT ELEMENTS PLUS SIX OPTIONAL ONES IF THEY'RE APPLICABLE TO THAT KIND OF RESEARCH. NOW, THERE ARE DISCLOSURE ELEMENTS OR BRAIN DEVELOPMENT FOR EXAMPLE, THE INTERVENTION RELATED CHANGES WE TOUCHED ON BEHAVIOR, PERCEPTION, MOOD PERSONALITY AND PERSONALITY GOT A LONG DISCUSSION TODAY. THIS STRIKES TO THE HEART OF THE THINGS THAT MAKE US WHO WE ARE AS PEOPLE AND THAT'S WHY IT SEEMS TO BE A PARTICULARLY SALIENT ISSUE WHEN THERE ARE UNFORESEEABLE BUT PERHAPS WHEN IT HAPPENS WORE NOT SURPRISED KINDS OF RISKS AND CHALLENGES IN COMMUNICATING THE RISKS. I KNOW HANNAH WILL TALK ABOUT THE TOPIC. DECISION-MAKING CAPACITY A LONG SALIENT ISSUE AND YOU HEARD MY BACK AND FORTH WITH JOE. WHEN HE DID THE GROUND-BREAKING RESEARCH WITH HIS TEAM THERE'S AN ISSUE OF HOW DO YOU GET CONSENT WHEN THE PERSON CAN'T CONSENT. SO WE KNOW THAT SOME RAIN DISORDERS IMPAIR ONE'S ABILITIES TO SUCH AN EXTENT THAT YOUR DECISION-MAKING CAPACITY IS NOT THERE. THAT IS NOT TO SAY THAT DIAGNOSIS EQUALS INCAPACITY. INSTEAD OUR MODERN FRAMEWORK LOOKS AT THE ACTUAL FUNCTIONAL ABILITIES. STILL, DECISIONAL CAPACITY IS EFFECTIVE IN ORDERS OF CONSCIOUS AND DEMENTIAS AND BRAIN INJURIES, CHRONIC PSYCHOTIC DISORDER AND ELEVATED RISK OF INCAPACITY AND DEPRESSION IS PRETTY COMPATIBLE WITH CAPACITY EXCEPT WHEN PEOPLE GET SEVERELY DEPRESSED WITH PSYCHOTIC SYMPTOMS. SEVERE EATING DISORDERS AND SOME TYPES OF LANGUAGE DISORDERS. NOW, THIS IS A VERY RELEVANT ISSUE FOR BRAIN DEVICE RESEARCH AS WE HAVE ALREADY SEEN. UNFORTUNATELY, THE REGULATORY FRAMEWORK IN WHICH WE THINK ABOUT THIS ALONG WITH THE ETHICS OF IT HAS BEEN A FLOATING ISSUE THROUGHOUT THE HISTORY OF AMERICAN RESEARCH ETHICS FOR THE PAST SEVERAL DECK 80s. DECADES. FEDERAL REGULATION ALLOW LEGALLY AUTHORIZED REPRESENTATIVE. THAT'S WRITTEN INTO THE COMMON RULE BUT LAR IS REGULATED BY LOCAL AND STATE REGULATIONS. LIVING IN A FEDERAL SYSTEM THE REGULATORY LAW SAYS WITH A LITTLE LET OTHER JURISDICTIONS DECIDE IT. BECAUSE SURROGATE DECISION MAKING FOR HEALTH RELATED THINGS IS THE PURVIEW OF STATES. I WOULD NOTE THAT CHRISTINE REMINDED ME OF THIS, IF THE NEW REVIVED COMMON RULE GOES INTO EFFECT WHICH IS SCHEDULED FOR 2018 AND MAY BE 2019 WE THINK, IF THAT GOES INTO EFFECT ONE THING THAT USED TO HAPPEN AND INSTITUTIONS HAD TO DO A RISK MANAGEMENT APPROACH AND DIFFERENT AGENCIES WOULD HAVE DIFFERENT REGULATIONS. THAT IS TRUE IN NEW YORK CITY FOR EXAMPLE. NOW, IT MAY BE THAT INSTITUTIONAL POLICIES WILL BE GIVEN AT LEAST FROM THE FEDERAL REGULATORY PERSPECTIVE AN OFFICIAL RECOGNITION WHICH WILL ALLOW INVESTORS TO MEET THE FEDERAL REQUIREMENTS IN TERMS OF FOLLOWING LAWS OF LAR. NOW THIS DOESN'T DIRECTLY EFFECT WHAT THE STATES WILL DO. IF THEY HAVE REGULATIONS AND CERTAIN SAY IN RESEARCH REGULATION IT DOESN'T AUTOMATICALLY TRUMP THAT PERFORM INCONSISTENCY. SO THE OTHER ISSUE IS THAT THERE ARE FEW STATES NOW IN WHICH WHAT I WOULD CALL MODERN RESEARCH REGULATIONS IS IN PLACE. SO THAT WOULD BE NEW JERSEY, CALIFORNIA, VIRGINIA, PAIR MAYOR THROUGH A STATEMENT THROUGH THE ATTORNEY GENERAL'S OFFICE AND WE'RE KIND OF A FEDERAL ENTITY WITH OUR OWN RULES. ALL THESE DOCUMENTS PLACE LIMITS ON THE RISK OKAY. WE HAVE A TERM WHERE PEOPLE ARE PRESSURED INTO. YOU MAY THINK IT'S UNDUE INFLUENCE BUT HEY. NOW FOR ETHICISTS RESEARCHES AND THESE BRAIN DISORDERS ARE DEBILITATING, DISTRESSING. SO IF THE PATIENT HAS A VERY SERIOUS CONDITION AND DESPERATE TO TRY ANYTHING, HOW VOLUNTARY IS SUCH A PERSON'S CHOICE? THIS IS A RECURRENT THEME AND POINT OF DISCUSSION AT MEETINGS LIKE THIS. NOW, THERE ARE TWO VIEWS I WOULD SAY. I'M SIMPLIFYING THE FIELD OF BIOETHICS AND IRB DISCUSSIONS AND SO FORTH ABOUT THE TOPIC INTO TWO SCHOOLS OF THOUGHT. ANY SIMPLIFICATION WILL HELP US START. I KNOW FRANK WILL PUT LOTS OF NUANCES AN MORE ON THIS. SUCH TO SAY SUCH PERSONS ROUTINELY MISCONCEIVE THE PURPOSE OF THE STUDY, DON'T UNDERSTAND THE RISK AND OVER ESTIMATE THE BENEFITS THEREFORE IT'S A COMMON THING PEOPLE DON'T KNOW WHAT THEIR DOING WHEN THEY GET INTO RESEARCH AND IT'S AN ALARMING ETHICAL SITUATION. I WOULD SAY IF PUSH COMES TO SHOVE IF WE HAD TO TAKE POLLS AT MEETINGS OF IRB STAFF AND SO FORM OR RESEARCH THAT WOULD HAVE A POPULAR SUPPORT. NOW THE OTHER VIEW IS THE FOLLOWING. SUCH PERSONS UNDERSTAND THE ISSUES FINE JUST LIKE ANYBODY ELSE WOULD BUT AT RISK OF UNWISELY GETTING THEIR HOPES UP TOO MUCH IN THE VERY COLLOQUIAL SENSE. BUT THIS IS NORMAL HUMAN NATURE, NOT UNDERSTANDING. WE SHOULDN'T CONFUSE MISUNDERSTANDING WITH MOTIVATION. I MAY BE MOTIVATED TO WIN THE LOTTERY BUT I KNOW PRETTY DARN WELL I'M NOT GOING TO WIN IT, RIGHT? IT'S SOMETHING WE SHOULD ANTICIPATE AND ADDRESS BUT IT SHOULDN'T BE TAKEN AS A VIEW THAT PEOPLE JUST BECAUSE THEY BECOME RESEARCH SUBJECTS THEY CAN'T UNDERSTAND THINGS. WHAT I WOULD SAY ON THE TOPIC IS IT'S NOT WRITTEN INTO REGULATIONS OR HOW WE TEACH PEOPLE HOW TO OBTAIN FOREIGN CONSENT BUT THERE'S SOMETHING RESEARCHERS IN THIS SETTING SHOULD ALWAYS ASK, HAVE A DISCUSSION AND EXPLAIN THE STUDY AND ASK THE PATIENTS OR SUBJECTS AND SAY YES I WANT TO BE IN THE STUDY, I BELIEVE YOU SHOULD ALWAYS OKAY, YOU SAID YOU'D LIKE TO BE IN THE STUDY, CAN YOU TELL ME WHY? THAT'S NOT REQUIRED BY REGULATIONS BUT IF YOU ASK THAT QUESTION YOU WILL HAVE A VERY FRUITFUL CONVERSATION THAT'S REASSURING TO THE SUBJECT AND YOURSELF. SUMMARY. INFORMED CONSENT IS ONE OF MANY ETHICAL REQUIREMENTS AND THERE ARE ISSUES FOR BRAIN DEVICE RESEARCH. I SUSPECT WE'LL GET LOTS MORE DETAILS AND INTERESTING ISSUES BROUGHT UP WITHIN THE NEXT SPEAKERS. THANK YOU. >> GREAT. SO THANK YOU VERY MUCH FOR THE INVITATION TO COME AND SPEAK HEAR. I'M -- COME AND SPEAK HERE. THERE'S A NEW TECHNOLOGY BEING DEVELOPED BY A GROUP OF RESEARCHERS. I'M INVOLVED IN THEIR PROJECT. THEY ARE ATTEMPTING TO DEVELOP NEUROTECHNOLOGY FOR SPEECH. THEY'LL BE PROMPTING DEVICES THAT WILL RECORD BRAIN ACTIVITY FROM AN AREA OF THE BRAIN THAT WILL HAVE BRAIN ACTIVITY THAT CORRESPONDS TO SOMETHING MEANINGFUL ABOUT SPEECH PRODUCTION AND THIS ACTIVITY THERE BE DECODED AND SYNTHESIZED AS SPEECH. THE POPULATIONS THAT MAY USE THEM ARE PATIENTS WITH SYNDROMES OR OTHER PATIENTS WITH SEVERE APHASIA. THIS IS BRINGING SCIENTISTS ALONG THE SPECTRUM OF RESEARCHERS. WE HAVE ENGINEERS WORKING ON THE NANO TECHNOLOGIESES PRODUCING MICROELECTROTOPOGRAPHY AND NEUROSCIENTISTS WORKING ON DECODING HUMAN SPEECH AND OFFICERS ON THE TRANSLATIONAL END OF THINGS. THIS DIAGRAM REPRESENTS THE ASPIRATION BEYOND THE TECHNOLOGY. THERE WILL BE ELECTRODE RECORD THE TECHNOLOGY. I'LL TALK ABOUT WHY THE CHOICE OF LOCATION OF RECORDING SITE MAY MAKE A MEANING DIFFERENCE TO THE ETHICAL DISCUSSIONS WE'RE HAVING ON THIS PANEL. THE REST OF THE PROCESS WILL INVOLVED INTERFACE TECHNOLOGY TO DECODE THE SIGNALS AND SYNTHESIZE THE ACTIVITY AS EXTERNALIZED SPEECH. THIS IS FROM A PUBLICATION LED BY COLLEAGUES THAT HAS BEEN PUBLISHED IN THE JOURNAL OF PHYSIOLOGY RECENTLY. THE MAIN OBJECTIVE OF THE PROJECT ARE TO DEVELOP A NEW GENERATION OF NEUROPROSTHETIC DEVICES FOR HIGH DENSITY RECORDING AND AT SOME POINT STIMULATION OF THE HUMAN CORTEX SUITABLE TO EXPLORE AND REPAIR HIGH LEVEL COGNITIVE FUNCTION AND THE PARTICULAR ONE OF INTEREST IS SPEECH CAPACITY. THE IDEA BEHIND HOW THIS WILL WORK IS ARTIFICIAL SPEECH SYNTHESIS WILL ALLOW CONTINUOUS DECODING OF COVERT SPEECH. THAT'S WHEN PARTICIPANTS OR PATIENTS IMAGINE SPEAKING IN THEIR HEAD SO IMAGINE IF YOU SHOUT REALLY LOUDLY IN THEIR HEAD THIS IS AN INSTANCE OF COVERT SPEECH AND THE ACTIVITY IMAGINED CAN BE USED TO DECODE AN EXTERNALIZED SYNTHESIZED SPEECH. IN THIS DEVICE THERE'S TWO ISSUES IN OBTAINING INFORMED CONSENT WE NEED TO CONSIDER. ONE IS NOT PARTICULARLY NOVEL OR UNIQUE TO THIS KIND OF TECHNOLOGY THOUGH THE SECOND MIGHT BE. I'LL GO PRESENT THOSE IN A MOMENT. AND IT'S NOT JUST READING FACTS TO THE PATIENT AND GETTING THE SIGNATURE. IT'S A PROCESS. AND PATIENTS WITH APHASIA ALREADY HAVE A PROBLEM IN THE PROCESS OF INFORMED CONSENT. THE CAPACITY WE'D NEED TO LOOK AT AS WELL BUT WITH PATIENTS WHO CAN FULLY UNDERSTAND WHAT IS BEING IN UNDERSTANDING AND THERE'S STILL A CHALLENGE IN DISCUSS. PHYSICIANS DON'T ONLY PROVIDE FACTS BUT ENGAGE IN DISCUSSION OF THE FACTS AND THE PATIENT'S VALUES. WE HEARD EXAMPLE OF HOW THE SAME TECHNOLOGY CAN BE EXPERIENCED DIFFERENTLY BY DIFFERENT PATIENTS. THIS IS ALL PART OF GETTING AN UNDERSTANDING OF WHETHER USING A THERAPY OR DEVICE WILL BENEFIT THE PATIENT OR WHETHER THE PATIENT WANTS TO GO AHEAD. THIS IS OFTEN A PREREQUISITE FOR UNDERSTANDING DECISION MAKING TO MAKE A VOLUNTARY DECISION. SO I KNOW SOME OF YOU HAVE ALREADY WORKED ON THESE MODELS OF LIBERAL RATIONALISM OR PATIENT DIALOG WHERE THE MODEL IS DOCTORS AND PATIENTS ENGAGE ON WHICH COURSE OF ACTION IS BEST FOR THE PATIENT. WHEN IS YOU A PATIENT WITH KNOWN COMMUNICATION LIMITS ENGAGE MANY IS A PROCESS. THERE'S TWO THINGS TO CONSIDER. ONE IS DIRECTLY RELATING TO THIS PROCESS AND TALKING TO PATIENTS ABOUT THE TECHNOLOGY. THESE CHALLENGES ARE GOING TO BE MOST ACUTE AS THE TECHNOLOGY NEAR ADOPTION AND THOSE WHO HAVE EXTREME PROBLEM WITH COMMUNICATION. THERE'LL BE MORE TO UNDERSTAND AT THAT POINT BECAUSE THE TECHNOLOGY IS VERY COMPLICATED. THE MECHANISMS ARE SOPHISTICATED AND PERHAPS QUITE ESOTERIC TO PATIENTS BUT THERE'LL BE GREATER DIFFICULTIES WITH THE DISCUSSION. THEN WE'LL DISCUSS A RELATED CHALLENGE THAT IS MORE UNIQUE TO THE TECHNOLOGY. THIS HAS TO DO WITH ENGAGING IN THE INFORMED CONSENT PROCESS WITH PATIENTS TALKING THROUGH THE TECHNOLOGY. THESE CHALLENGES ARE GOING TO BE MOST ACUTE WHEN IT'S USED BY PATIENTS ENTIRELY WITHOUT ALTERNATIVE MEANS OF COMMUNICATION. SO BACK TO THE FIRST CHALLENGE. AS I'VE SAID ENGAGING IN DISCUSSION ABOUT THE TREATMENT OR THE TECHNOLOGY IS IMPERATIVE IF WE WANT PARTICIPANTS OR PATIENTS TO BE SUFFICIENTLY INFORMED ON WHAT THEY'RE SIGNING UP TO. THERE ARE GOING TO BE A RANGE OF CHALLENGES RELATING TO THESE KINDS OF DEVICES. A LOT OF RESEARCH IS NEEDED BEFORE WE CAN EVEN KNOW AND CONCEPTUALIZE THE RANGE OF POSSIBILITIES FOR THE MECHANISM FOR THIS DEVICE. AS I SAID THE LOCATION OF THE RECORDING SITE IS GOING TO BE RELEVANT HERE. THERE ARE DISCUSSIONS ON WHETHER TO USE BRAIN AREAS THAT UNDER PIN THE ACOUSTIC PROPERTIES OF SPEECH OR UNDER PIN ARTICULATORY AND WHAT WILL BE RECORDED AND DECODED WILL BE RELATED TO THE LIP AND TONGUE AND MOUTH AND RELATED TO ACOUSTIC FEATURES. SO IT'S QUITE DIFFICULT TO CONCEPTUALIZE THE DEVICE WILL DO AT THIS STAGE OF RESEARCH. AND EVEN ONCE DEVICES ARE BEING ROLLED OUT AND USED BY PATIENTS IT'S GOING TO BE DIFFICULT AS WELL TO DISCUSS WITH THEM WHAT EXACTLY IT WILL ENABLE THE PATIENT TO DO AND HOW THE PATIENT WILL USE IT. YOU'LL SEE ON THE SLIDE OF THE OBJECTIVES IT TALKED ABOUT REPAIRING COGNITIVE FUNCTION. I DON'T THINK IT'S JUST A POINT OF PEDENTRY TO RESTORE THE CAPACITY FOR SPEECH OR SEEN MORE OF A SUBSTITUTE COMMUNICATION TOOL OR SOMETHING ALONG TEASE LINES. ALONG THESE LINES. THERE'LL BE VERSIONS OF MISCONCEPTI MISCONCEPTI MISCONCEPTION IN AS FAR AS WELL APPROXIMATE BUT STILL A USEFUL TOOL AND AVOID THE VOYEURISTIC COMMUNICATION. THAT PATIENTS MAY REASONABLY THINK IF THEY IS A DEVICE READING THEIR BRAIN ACTIVITY RELATE TO WHAT THEY SAY IN THEIR HEAD IT WILL BE A MIND READER AND ENABLE INDIVIDUALS TO LOOK INSIDE THEIR MINDS OR THEIR MINDS WON'T BE AS PRIVATE AS THEY ONCE WERE. AND DISCUSSING THE CAPACITY IT WILL ENABLE WILL REMAIN A CHALLENGE FOR THE PATIENTS. YOU HAVE A COMPLICATED AND ESOTERIC DEVICE AND IT'S NOT LIKE A PROSTHETIC ARM AND THAT ARE PERHAPS UNABLE TO ASK THE QUESTIONS THAT NEED TO BE ASKED TO SUFFICIENTLY UNDERSTAND THE DEVICE AND ALL THE WAYS IT MAY EFFECT THEIR EXPERIENCES. AND TO CONSENT TO OTHER MEDICAL TREATMENT OR PALLIATIVE TREATMENT AND SO WITH THE DEVICES WHEN PATIENTS ARE COMMUNICATING ENTIRELY VIA THE PROSTHESIS, WE'LL BE CONCERNED BOTH ABOUT THE ACCURACY OF THE REPRESENTATION OF THE PATIENT IN A SPEECH. WHAT IS EXTERNALIZED AND WHETHER THAT REALLY RESPONDS TO THE THOUGHTS OR INTENDED SPEECH THE PATIENT HAS IN THEIR HEAD. IT'S NOT THE CASE WHEN WE SPEAK NATURALLY EVERYTHING WE SAY IS WELL REFLECTED ON AND NECESSARILY ENDORSED AT THE POINT IT LEAVES OUR MOUTHS BUT I THINK THERE MAY BE A REASONABLE CONCERN WITH THE SHORTER GAP, PERHAPS, THOUGHTS OR LINGUISTIC STRUCTURES IN THE PATIENTS HEAD AND WHAT IS EXTERNALIZED VIA THE SYNTHETIC PROSTHESIS. THIS IS GOING TO BE COMPLICATED FURTHER BECAUSE THEY'LL LIKELY HAVE ASPECTS OF AI TO CORRECT THE SPEECH AS IT'S BEING EXTERNALIZED CONTINUOUSLY. HERE WE HAVE ANOTHER ARTIFICIAL AGENT THAT MAY EFFECT WHAT IS EXTERNALLY EXPRESSED. SO THERE ARE GOING TO BE INTERESTING QUESTIONS HERE WHETHER THE SPEECH THAT IS EXTERNALIZED IF PREDICTED AND CORRECTED USING TO SOME EXTENT USING AI IS A PROPER REPRESENTATION OF WHAT THE PATIENT INTENDED TO SAY. THEY HAVE PARALLELS WITH PROBLEMS AND CHALLENGES THAT ALREADY OCCUPY PHYSICIANS ON A DAY TO DAY BASIS. BUT WITH THIS PARTICULAR TECHNOLOGY WE MAY NEED TO INTRODUCE SURROGATE INTERPRETERS AND OTHER SAFEGUARDS AT THE POINT OF OBTAINING FULL CONSENT TO MAKE SURE THE CONSENT REALLY IS AS ROBUST AS IT NEEDS TO BE. THERE'S ALSO QUESTIONS WITH HOW FINE GRAINED THE DECISION NEEDS TO BE. IT MAY BE OKAY IF THE PATIENT CAN SAY A FEW WORDS AND FOR MORE IMPORTANT DECISIONS WE WANT TO MAKE SURE THIS PATIENT IS ABLE TO EXPRESS THEMSELVES IN A FULSOME ENOUGH WAY. SO I'LL LEAVE THAT THERE AND LOOK FORWARD TO COMMENTS AND SUGGESTIONS. >> WE HAVE A STAFF NEUROLOGIST FOR THE VA AND AT THE UNIVERSITY OF WASHINGTON IN NEUROLOGY AND AFFILIATED WITH THE CENTER FOR SENSORY AND NEUROMOTOR CENTER. >> IT TOOK ME SEVERAL YEARS TO SAY THAT IN THE CORRECT ORDER SO THAT'S PRETTY IMPRESSIVE. I WAS THINKING ABOUT RISKS AND BENEFITS OF HAVING ONE'S TALK AT THIS POINT IF THE DAY AFTER FOLLOWING SO MANY INTERESTING TALKS AND PEOPLE WHO HAVE HIGHLIGHTED SUCH IMPORTANT TALKS DURING THE DISCUSSION. I'M GOING TO TALK ABOUT INFORMED CONSENT FROM THE CONCEPT OF IMPLANTED NEURAL TECHNOLOGIES. IT'S WHAT WE TRIED TO USE RATHER THAN INVASIVE BUT GIVEN THE DISCUSSIONS TODAY EVEN THAT IS IMPERFECT AND IMPRECISE. MY HOPE IS THOUGH I'M GOING TO TALK ABOUT TECHNOLOGY RELATED TO THE FOCUS OF OUR CENTER AT THE UNIVERSITY OF WASHINGTON WHICH IS BRAIN TECHNOLOGY DEVICES I'M HOPING SOME OF THE THINGS I'LL SAY WILL HAVE REFERENCE TO BOTH IMPLANTABLE AND OTHER NON-IMPLANTABLE DEVICES. ONE WAY TO THINK ABOUT THINKING THROUGH THE IDEA ON INFORMED CONSENT IN TERMS OF THE FUNCTIONAL DOMAINS IN WHICH THE DEVICES CAN BE TARGETED. IN OUR CENTER, WE HAVE MOSTLY FOCUSSED ON MOTOR AND SENSORY. THERE'S A PROJECT AS WAS MENTIONED BEFORE THAT USED A CLOSE-LOOPED CENTER FOR CENTRAL TREMOR AND WE HAVE PROJECTS LOOKING AT SENSORY RESTORATION AFTER STROKE OR SPINAL CORD INJURY. BUT OBVIOUSLY AS HAS BEEN MENTIONED BEFORE THERE'S LOTS OF POTENTIAL OUTPUT DEVICES FOR BRAIN INTERFACE TECHNOLOGY, WHEELCHAIRS, LIMB PROSTHETICS AND COMMUNICATION DEVICES AS WAS DISCUSSED. I'M GOING TO IN A MINUTE TALK THROUGH THE USE OF BCI IN PSYCHIATRY MAINLY BECAUSE WE DID A QUALITATIVE STUDY WITH INDIVIDUALS WHO HAD DBS FOR DEPRESSION AND OCD AND I WANT TO USE THAT TO HIGHLIGHT SOME OF THE THINGS I WANT TO SAY. SO I PUT THIS SLIDE BACK UP HERE TO REMIND US OF THE PILLARS OF INFORMED CONSENT AND STRUCTURE WHAT I WANT TO TALK ABOUT HERE. SO PLEASE BEAR WITH ME. GIVEN ALL THAT'S COME BEFORE I'LL ADJUST A LITTLE BIT ON THE FLY AND THERE ARE STANDARD RISKS OF INFORMED CONSENT WHICH HAVE BEEN DISCUSSED TODAY. SO RISKS AROUND SURGICAL IMPLANTATION AND ALSO AROUND BIOCOMPATIBILITY OF LEAVING ELECTRODES IN FOR SHORT AND LONG PERIOD OF TIME THAT WE NEED TO CONSIDER. THEN THERE ARE ALSO COGNITIVE AND PSYCHIATRIC EVENT WHICH IS HAVE BEEN DISCUSSED. WE CAN LOOK TO THE LITERATURE ON DBS FOR A THE DEBATE WHETHER IT MAKES DEPRESSION WORSE OR DEMENTIA WORSE. THOSE ARE IMPORTANT DEBATES FOR THE FIELD TO SETTLE ON. THEY SHOW RAPIDLY CHANGING TRANSLATION OF DEVICES AND A RISK THAT THE SEVERITY OF WHICH AND THE FREQUENCY OF WHICH ARE HARD TO KNOW EVEN AT THE TIME IN WHICH STUDIES ARE ON GOING AND SUBJECTS HAVE TO BE COUNSELLED. WHAT DO YOU TELL SUBJECTS? WHAT DO YOU DISCLOSE AND NOT DISCLOSE? WHAT'S YOUR THRESHOLD FOR DISCLOSING AN ADVERSE EVENT? FOR INSTANCE, IF THERE IS AN ADVERSE EVENT THAT IS SORT OF A COLLEGIATE A DIFFERENT INSTITUTION HAD BUT YOU DON'T KNOW THE DETAILS AND IS THAT THE THING YOU DISCLOSE TO YOUR SUBJECTS OR FOT? -- OR NOT? THESE ARE HARD QUESTIONS. IN ADDITION TO WHAT I CALL STANDARD RISKS, THERE'S FOR LACK OF A BETTER TERM ATYPICAL RISKS WE DON'T TYPICALLY TALK ABOUT THEM AND THESE ARE RISKS THAT USERS OF NEURAL DEVICES CAN EXPERIENCE AND AFFECT THEIR QUALITY OF LIFE BUT AS MENTIONED BEFORE WE MIGHT NOT HAVE ESTABLISHED MEASURES FOR DETERMINING WHETHER THESE ARE IN FACT OR HOW TO GET OUR HEADS AROUND WHAT THEY MEAN OR WHAT THEY MEAN TO SUBJECTS. I WANT TO ELABORATE ON THESE WITH A STUDY WE DID IN BOSTON WITH INDIVIDUALS WHO HAD GOTTEN DBS FOR DEPRESSION OR OECD AND MONITORED THEM TO FIGURE OUT THEIR PERSPECTIVES ON THE PROSPECT OF USING CLOSE-UP SYSTEMS. THEY HAD OPEN-LOOP DBS. BUT IN THE PROCESS THERE'S SOME INTERESTING THINGS THAT CAME OUT OF THIS IN TERMS OF ATYPICAL RISK AND INFORMED CONSENT. THERE'S A CHALLENGE IN ONE PARTICULAR AREA. THE QUOTES I'M GOING TO SHOW YOU AREN'T MEANT TO BE REPRESENTATIVE OF EVERYONE IN THE STUDY OR EVEN OR REPRESENTATIVE ON THE FEEL OF TECHNOLOGY BUT TO PUT FLESH ON THE ABSTRACT CONCERNS. THERE'S A SENSE OF IDENTIFY AND ATHENTICITY. IT TOOK TWO FORMS. ONE IS PEOPLE FELT AFTER HAVING THE DBS IMPLANTED THEY WERE ABLE TO GET BACK TO WHO THEY WERE. TO THEIR CORE SELF AND WERE UNDERNEATH THE DEPRESSION. IT GOT TO THE ME WITHOUT THE DEPRESSION. THERE WERE PEOPLE WHO FELT AFTER THE DBS THEY WERE ABLE TO BECOME THE PERSON THEY ALWAYS WANTED TO BE. MORE OF A CREATIVE SENSE OF AUTHENTICITY. THEY WERE UNSHACKLED. AND THIS IS THE MOTION OF AUTHENTICITY IS WHAT WE SEE NEURAL PHARMACOLOGY AND WHAT STRUCK US IS HOW OFTEN WE HEARD THIS IN OUR FOCUS GROUP AND THE EXPLICITNESS WITH WHICH IT WAS MADE KNOWN TO US. IS THE THING I'M THINKING AND FEELING AND DOING IS THIS COMING FROM ME OR IS THIS COMING FROM THE DEVICE I HAVE? THIS UNCERTAINTY ABOUT THAT. THAT'S WELL ENCAPSULATED IN THE FIRST QUOTE. IT'S ME AND IT DEPRESSION AND THE STIMULATOR. MOST PEOPLE EXPRESSED THIS IN TERMS OF THEM FEELING UNCERTAINTY BUT WE HAD A FEW PEOPLE WHO SORT OF TALKED ABOUT THIS IN TERMS OF THEIR FAMILY MEMBERS OR OTHERS SOMETIMES POINTING TO THE DEVICE AS MAYBE BLAMING THEM FOR THE DEVICE OF WHY ME PERSON WAS ACTING WHY THEY WERE AND SOMETIMES ATTRIBUTING THAT TO THE PERSON. IT WASN'T JUST FIRST PERSON. THE LAST THING I WANT IT TALK ABOUT IS PRIVACY. THERE WAS THIS CONCERN NOT SO MUCH WITH THE NEUROSECURITY CONCERN OF SOMEONE MALICIOUSLY HACKING INTO BRAIN DATA COLLECTED PERFECT THE DEVICES BUT MORE THE SENSE THAT THERE'S MAYBE ANYTHING DIFFERENT ABOUT THE BRAIN DATA AND SOMETHING IN THERE. THERE'S A CONCERN THAT RESEARCHERS OR OTHERS MAY BE ABLE TO INFER THINGS ABOUT YOU. DO I GET AND HOU-- ANXIOUS OR EXCITED WHEN I WIFE WALKS IN THE ROOM. GI GIVEN THE TIME CONSTRAINTS I WON'T GET INTO IT BUT WE WERE STRUCK BY MAYBE THE LACK OF UNDERSTANDING AND LACK OF APPRECIATION AMONG SOME INDIVIDUALS. SO WE HAD A NUMBER OF INDIVIDUALS WHO FELT WE COULDN'T EVEN READ THE CONSENT FORM. I COULDN'T COMPREHEND IT. MY COMPREHENSION WAS SO BAD I HAD TO RELY ON FAMILY. THEN IN TERMS OF APPRECIATION, PEOPLE FELT I COULD CARE LESS ABOUT THE RISKS. I DIDN'T CARE. SOME OF THIS MAY BE SPECIFIC TO SEVERE DEPRESSION OR OCD, WE HEARD THE SENSE THAT PEOPLE REFLECTING FELT THEY HAD UNREALISTIC EXPECTATIONS GOING IN AND THE QUOTE AT THE BOTTOM, THE INDIVIDUAL SAID FOR ANYONE TO GET BRAIN SURGERY HOW CAN THEY GET IT WITHOUT BELIEVING IT'S GOING TO BENEFIT THEM. SO I WANT TO END BY MAYBE PUTTING ON THE TABLE SOME POTENTIAL IDEALS WE MIGHT THINK ABOUT AS WE THINK THROUGH INFORMED CONSENT PROCESSES. AND KNOWING THE TECHNICAL AND CLINICAL RISKS YOU NEED PEOPLE WIN EXPERTISE IN ALL THE AREAS, NEUROSCIENTISTS, ENGINEERS, CLINICIAN AND PSYCHOLOGISTS IN THE ROOM AT SOME POINT IN DEVELOPING INFORMED CONSENT PROCESSES. THIS IS SOMETHING PAUL FORD IN PARTICULAR HAS WRITTEN COGENTLY ABOUT. IT NEEDS TO BE SYSTEMATIC AND APPARENT. IF WE DON'T KNOW ALL THE RISKS WE NEED TO BE TRANSPARENT IN THE COMMUNITY AND WITH PARTICIPANTS AND THERE NEEDS TO BE A PROCESS THAT GETS REVISITED THROUGHOUT A TRIAL PARTICULARLY WITH THE LONG TRIALS OVER YEARS. AND GET TO ONE OF THE THINGS JOE MENTIONED THAT ARE RELATIONAL. WE NEED TO RECOGNIZE THAT PARTICIPATION IN THESE TRIALS INVOLVED FAMILY IN MANY WAYS. AND IT NEEDS TO BE EXPLORATORY AND EXPECTATIONS AND HOW VOLUNTEERING FOR THE TRIALS FITS INTO THAT AND WHERE THEY SEE THEMSELVES IN THE FUTURE. SO WITH THAT I WANT TO THANK MY TEAM HERE. >> THE LAST PANELIST IS DR. FRANK MILLER Ph.D. PROFESSOR OF MEDICAL ETHICS AT CORNELL AND WAS FOR MANY YEARS FACULTY HERE -- [INAUDIBLE]. >> SO I THINK WE REACHED THE TIME OF THE DAY WHERE WE CAN USE BRAIN STIMULATION. I'LL TALK ABOUT THE PHENOMENON KNOWN AS MEDICAL MISCONCEPTION MENTIONED IN PREVIOUS TALKS. I'M GOING TO PLACE IT IN THE CONTEXT OF -- AND IT'S ALSO A TOPIC OF WHICH MANY PEOPLE RAISES SERIOUS PROBLEMS ON INFORMED CONSENT. I'M GOING TO TALK ABOUT THIS PHENOMENON IN TRIALS FOR NEUROLOGICAL AND PSYCHIATRIC PATIENTS. THE TERM WAS COINED IN 1982 BASED ON A SERIOUS OF INTERVIEWS, STUDIES WITH PSYCHIATRIC PATIENTS INVOLVED IN RANDOMIZED CONTROL TRIALS. THE APPLEBAUM GROUP HAS BEEN WORKING ON THIS STEADILY THE LAST 35 YEARS. THE TM PHENOMENON INVOLVED THE TAN -- TEND TENDENCIES AND PATIENT SUBJECTS BELIEVE THEIR TREATMENT WILL BE MANAGED ON PHYSICIAN'S JUDGMENTS ON WHAT'S BEST FOR THEM. THERE'S VARIOUS EXAMPLES OF A THERAPEUTIC MISCONCEPTION. ONE IS A BELIEVE BY A BELIEF THAT THE MAJOR PURPOSE OF A RANDOMIZED OR PHASE 1 TRIAL SO TO BENEFIT TRIAL PARTICIPANTS. THERE COULD BE FAILURE TO UNDERSTAND SELECTION IS RANDOM RATHER THAN A CLINICAL JUDGMENT ON WHAT'S BEST FOR PATIENTS. FAILURE TO UNDERSTAND WHAT'S INVOLVED IN GETTING A PLACEBO CONTROL AND IT'S EXPERIMENTAL. WAS THEY GO INTO A TRIAL FOR A CHANCE OF THERAPEUTIC BENEFIT DOESN'T MEAN THEY'RE CONFUSED ABOUT THE RISK BENEFIT PROFILE OF THE RESEARCH. APPLEBALM AND HIS COLLEAGUES DID INTERVIEWS AT DOCUMENTING THE EXTENT AND PREVALENCE OF THERAPEUTIC MISCONCEPTION AND THEY FOUND OVERALL A PREVALENCE OF 60% IN A WIDE RANGE OF CLINICAL TRIALS IN MANY DIFFERENT CONDITIONS. THIS INCLUDES A RECENT STUDY OF DEEP BRAIN STIMULATION WITH A PREVALENCE OF 60%. AND OTHERS THAT HAVE DONE WORK ON THIS DISPUTE WHETHER PATIENT SUBJECTS MANIFEST A THERAPEUTIC MISCONCEPTION WHEN YOU QUESTION THEM ON WHAT THEY UNDERSTAND ABOUT THE STUDY. I'M GOING TO BRACKET THIS METH LOGICAL DISPUTE FOR THE SAKE OF MY THOUGHT AND THEN ASK THE QUESTION WHAT BEARING DOES THIS HAVE ON THE VALIDITY OF CONSENT. I'M LOOKING AT DEEP BRAIN STIMULATION TRIALS AND WE'RE DEALING WITH REFACTORY PATIENTS WHO HAVE EXHAUSTIVE STANDARD TREATMENTS. I'LL USE THE "I" WORD, IT'S AN INVASIVE TREATMENT AND INTERVENTION TARGETING THE BRAIN AND THE STIMULATOR CAN BE ON AND THE PLACEBO EFFECT OF HAVING IT OFF AND STIMULATION AFTER. WHEN YOU LOOK AT DEEP STIMULATION THERE'S FACTORS THAT MAY SUGGEST THE PREVALENCE OF A THERAPEUTIC MISCONCEPTION AND ALSO A CONTEXT WHICH SUGGESTS MAYBE WE SHOULDN'T BE THAT WORRIED ABOUT THIS PHENOMENON. HERE'S SOME KEY ETHICAL QUESTIONS. DOES CONCEPT MEAN THEY'RE FREE OF THERAPEUTIC MISCONCEPTION? IF THE TM INVALIDATES CONSENT THAN SUBJECTS SHOULD BE EXCLUDED FROM TRIAL PARTICIPATION OR ENROLLED VIA SURROGATE CONSENT. DOES IT MATTER MORE FOR SOME TYPES OF TRIAL. IF YOU HAVE A PRAGMATIC STUDY COMPARING TWO MEDICALLY INDICATED STANDARD TREATMENTS FOR A GIVEN CONDITION. I DON'T THINK THERE'S MUCH REASON TO BE WORRIED ABOUT THE THERAPEUTIC MISCONCEPTION AND OTHER THAT HAVE RISK BENEFIT OR PROFILE OR CHARACTERISTICS MAY RAISE MORE CONCERNS AND WHAT STEPS SHOULD INVESTIGATORS TAKE TO COUNTERACT THE THERAPEUTIC MISCONCEPTION? FIRST IN ADDRESSING THE QUESTION IS ONE THE ERROR ON PATIENTS WHO MISUNDERSTOOD THE NATURE OF THE TRIAL AND WOULD REFUSE CONSENT IF THEY ACCURATELY UNDERSTAND. ON THE OTHER HAND THERE'S THE ERROR OF EXCLUDING CONSENTING PATIENTS WHO MISUNDERSTAND THE NATURE OF THE TRIAL BUT WOULD CONSENT IF THEY ACCURATELY UNDERSTAND. THIS IS ANALOGOUS OF TYPE 1 AND TYPE 2 ERRORS AND WE NEED TO BE CONCERNED ABOUT BOTH OF THEM. BASIC VALUE IS RESPECT FOR PERSONS AND INFORMED CONSENT AND IT'S AT STAKE FOR BOTH ERRORS. I THINK IT'S A FAILURE OF RESPECT FOR PERSONS TO INCLUDE SUBJECTS IN A TRIAL WHO SHOULD BE EXCLUDED AND FAILURE TO EXCLUDE SUBJECTS WHO SHOULD BE INCLUDED. AT LEAST IT'S MY BELIEF INCLUDING PATIENTS MAY FAIL TO RESPECT DECISIONS CONSISTENT WITH THEIR PREFERENCES AND VALUES. A KEY ISSUE VOLUNTARY CHOICE. WHICH SUBJECTS WHO MANIFEST THE MISCONCEPTION WOULD DECLINE IF THERE WERE NO THERAPEUTIC MISCONCEPTION? AND I'D LIKE TO SUGGEST BASED ON THE RISK BENEFIT PROL -- PROFILE OF THE STUDIES AND WHAT IS LIKELY TO BE THE MOTIVATING INTEREST OF THE PATIENT SUBJECTS THE ANSWER IS MORE LIKELY TO BE NO THAN TO BE YES. BACKING UP, WHAT DO SUBJECTS pCONSENT.NDERSTAND TO GIVE AND GIVEN ALL THE LITERATURE THERE'S NO CONSENSUS ON THE ANSWER TO THAT QUESTION. I WANT TO SAY BRIEFLY AND DOGMATICALLY IT'S MY VIEW SUBJECTS NEED A FAIR OPPORTUNITY TO UNDERSTAND MATERIAL INFORMATION ABOUT RESEARCH BUT DOUBTFUL THEY NEED TO UNDERSTAND ACCURATELY ALL THE ELEMENTS OF THE INFORMED CONSENT DISCLOSURE AND THE LANGUAGE AFFAIR OPPORTUNITY IS IN THE FEDERAL REGULATIONS. VARIOUS CONTEXTUAL VARIABLES ARE DIFFERENT AND THEY DIFFERENT WITH HOW SIGNIFICANT IT IS ETHICALLY FOR PATIENT SUBJECTS TO MANIFEST THE THERAPEUTIC MISCONCEPTION. AS THE RISK BENEFIT PROFILE BECOMES MORE UNFAVORABLE WE SHOULD BE MORE CONCERNED ABOUT THE THERAPEUTIC MISCONCEPTION. ALSO IF A TRIAL COMPARES INTERVENTIONS WITH MARKEDLY DIFFERENT CHARACTERISTICS SAY SURGERY VERSUS MEDICAL CARE, WE SHOULD BE CONCERNED ABOUT THIS PHENOMENON. AND IF STUDIES HAVE RESEARCH ON PROCEDURES TO PROSPECT OF MEDICAL BENEFIT SUCH AS A BIOPSY THAT'S A CONTEXT IN WHICH WE SHOULD BE CONCERNED ABOUT THE THERAPEUTIC MISCONCEPTION. ALSO IMPORTANT TO NOTE IS THERAPEUTIC MISCONCEPTION IS A MATTER OF DEGREE. SOME PARTICIPANTS MAY MANIFEST IT MORE OR LESS OR WHAT TRIAL PARTICIPATION INVOLVES. NOW, BECAUSE I DON'T THINK -- BECAUSE I DON'T THINK THE THERAPEUTIC MISCONCEPTION IN INVALIDATES CONSENT IT DON'T THINK INVESTIGATORS SHOULD NOT MAKE EFFORTS TO MINIMIZE IT. IT SHOULD START DIFFERENCE BETWEEN RESEARCH PARTICIPATION AND ROUTINE MEDICAL CARE AND AVOID LANGUAGE THAT CONFLATES THE ACTIVITIES. THERE'S A VARIETY OF ISSUES THAT SHOULD BE ADDRESSED IN THE DISCLOSURE PROCESS. THE PURPOSE OF THE TRIAL. THE FACT TREATMENT IS BEING SELECTED RANDOMLY. THE EXPERIMENTAL NATURE AND HOW THE TREATMENT MAY BE MASKED AND BLINDED THE RATIONALE OF A PLACEBO CONTROL AND THE RESTRICTIONS ON THE FLEXIBILITY OF TREATMENT AND UNDERSTANDING RESEARCH PROCEDURES THAT HAVE RISKS WITHOUT ANY COMPENSATING MEDICAL BENEFITS. ONE POSSIBLE SAFEGUARD SHOULD RAISE A CONCERN ON COMPREHENSION ON THE KEY ALMOSTS OF INFORMED CONSENT SUCH AS SUBJECT WHO'S FAIL TO PROVIDE ADEQUATE STATEMENT WOULD RECEIVE SOME EDUCATION AND POSSIBLY A SECOND TEST MAY LEAD TO EXCLUSION PERFECT TRIAL PARTICIPATION. I MYSELF DON'T BELIEVE ONE SHOULD DO A TEST OF COMPREHENSION IN A DEEP BRAIN STIMULATION TRIAL BUT THAT'S DEBATABLE AND I'D BE CONCERNED ON EXCLUDING PEOPLE ON BASIS OF FAILURE TO PASS THE TEST. IN CONCLUSION TO THERAPEUTIC MISCONCEPTION, POTENTIALLY THREATENS INFORMED CONSENT BUT DOESN'T NECESSARILY INVALIDATE INFORMED CONSENT AND THE PHENOMENON MATTERS DEPENDING ON THE TYPE OF TRIAL IN QUESTION AND OUR POLICY MEASURES RELATED TO INFORMED CONSENT SHOULD REFLECT THE GENERAL SIGNIFICANCE AND DIFFERENTIAL SALIENCE OF THE THERAPEUTIC MISCONCEPTION. THANKS. >> WE'LL HAVE THE PANELISTS COME FORWARD AND HAVE A DISCUSSION. >> I WAS TRYING TO BE PATIENT AND ALMOST GAVE UP. ENJOYED ALL THE TALK AND INTERESTING POINT. HANNAH, I WAS INTRIGUED BY THE VOYEURISTIC MISCONCEPTION. YOU THINK ABOUT AIRPORT WHOLE BODY SCREENING WHERE PEOPLE WERE CONCERNED ABOUT MODESTY AND BE ABLE TO SEE THE WHOLE BODY BECAUSE THE TECHNOLOGY WAS TO SHOW THE BODY AND THEY CHANGED -- IT WASN'T A MISCONCEPTION ON LOSING MODESTY, THEY CHANGED TECHNOLOGY TO MAP IT ON A STANDARD FIGURE. I CAN THINK OF THE VOYEURISTIC MISCONCEPTION SO I WONDERED HOW DO YOU MAKE SURE THE ENGINEERS BUILD IN PROTECTION SO IT IS A DIFFERENCE THAT CAN BE DISTINGUISHED. >> IT'S ANTICIPATION OF HOW THE TECHNOLOGY AND VOYEURISTIC IN THE WAY OF RELAYING ALL YOUR THOUGHTS OUT LOUD. AT THE MOMENT THE IDEA IS NEURALLY -- THERE WILL BE A DISTINCTION IN UNDERLIES COVERT SPEECH AND YOUR THOUGHTS. COVERT SPEECH WOULD BE TRYING TO SAY SOMETHING OR SHOUT SOMETHING IN YOUR AHEAD. WHEREAS THOUGHTS THAT DRIFT IN AND OUT OF YOUR MIND MAY NOT HAVE THE QUALITY. THERE COULD BE INSTANCE WHERE'S YOU SHOUT SOMETHING IN YOUR HEAD STRUCTURED IN THE SAME WAY AS COVERT SPEECH AND THIS IS AN ENGINEERING QUESTION HOW WE PREVENT THAT SORT OF THING BEING EXTERNALIZED. SOME OF THE SOLUTIONS BEING CONSIDERED ARE VERY SIMPLE THIS THIS WOULD DISRUPT THE POTENTIAL FOR THE PROSTHETIC SPEECH TO BE CONTINUOUS IS TO HAVE FEEDBACK, HEADPHONES TO THE USER AND THEY CAN SAY, YEP, PRESS NO OR DON'T EXTERNALIZE THAT. THAT MAY BE ONE WAY TO PUT IN THE REGULATORY CONTROL WE HAVE OVER WA -- WHAT WE EXTERNALIZE. WHEN I TALK ABOUT THE TECHNOLOGY EVEN TO SCIENTISTS THIS IS ONE OF THE THINGS THEY ALSO RISE IS HOW TO DIFFERENTIATE THE SPEECH INTERNALIZED VERSUS FLEETING THOUGHTS AND PATIENTS ARE GOING TO BE EVEN MORE CONCERNED. THERE'S POTENTIAL SOLUTIONS HAVING FEEDBACK THAT IS AND A BUTTON A POSSIBLE SOLUTION ENGINEERS ARE LOOKING AT. THANK YOU. >> Question: I SHOUT A LOT IN MY pHEAD AND MY QUESTION IS ON THEMAN CONCEPTION POINT. IT SEEMS WHAT WE WANT TO PAY ATTENTION TO IS THE CONSENT PROCESS AND IT MAYOR FOREGROUNDING OUR NEXT PANEL BUT DO WE STILL HAVE CONCERNS ON THERAPEUTIC MISCONCEPTIONS WHEN SOMEBODY IS MIDWAY THROUGH A TRIAL AND IT'S NOT HELPING THEM AND DO WE HAVE A DIFFERENT WORD FOR THAT? I'M NOT SURE HOW WE FRAME IT BUT IT SEEMS TO ME YOU CAN HAVE PEOPLE IN A FAILED TRIAL WHO SAY NO I THINK IT'S HELPING ME. IF WE DON'T HAVE A CLEAR MARKER TO SHOW THAT WE'LL HAVE THE SAME KINDS OF QUESTIONS AGAIN. >> WHEN HAVE YOU SUBJECTS MISUNDERSTANDING THE STUDY OR DON'T APPRECIATE THE INTERVENTION IS EXPERIMENTAL OR SAY THERE'S A RESEARCH PROCEDURE SOLELY TO UNDERSTAND THE QUESTION AND SAY WELL I'M GETTING THIS BECAUSE IT WILL HELP DIAGNOSE MY CONDITION I THINK YOU NEED TO CORRECT IT. IT'S PART OF THE CONVERSATION. BUT I DON'T THINK THAT MEANS WE'LL HAVE TO MAKE SURE THAT UNDER ALL CIRCUMSTANCES ANYBODY AT THE TRIAL AT THE BEGINNING OR END DEPENDING ON THE RISK BENEFIT IS FREE OF MISCONCEPTIONS. I THINK IF WE WANT TO RESPECT PEOPLE'S CHOICES BASED ON THEIR REFERENCES AND VALUES, MANY PEOPLE MAY WELL WANT TO BE IN A STUDY EVEN IF THEY ARE CONFUSED BUT HAVING THAT CONFUSION CORRECTED DOESN'T NECESSARILY CHANGE. >> THANKS EVERYONE FOR A REALLY INTERESTING PANEL. MY QUESTION IS FOR HANNAH. A TWO PART QUESTION. FIRST, I WONDERED IF YOU CAN SPEAK TO THE STATE OF THE SCIENCE ABOUT THESE KINDS OF DEVICES. I THINK I REMEMBER RESEARCH GOING ON AT BU WITH ARTICULATION AND IT WAS DIFFICULT. ARE THESE THINGS REALISTICALLY GOING TO BE VIABLE ANYTIME SOON. AND SECOND IS I WAS WONDERING WHICH ASPECTS OF THE ETHICAL CONCERNS YOU OUTLINED IN THE CASE OF BCI SPELLERS. PEOPLE CAN'T SPEAK BUT CAN COMMUNICATE USING SPELLING OF WORDS. >> IN TERMS OF THE STATE OF THE SCIENCE, IT'S QUITE NEW AND EARLY STAGES OF DEVELOPMENT THE STAGES I'M WORK IN HAS VARIOUS DIMENSIONS OF THE RESEARCH AT EARLY STAGES. THERE'S THE WORK WITH THE NANO MATERIALS MAKING EQUIPMENT TO USE IN THE DEVICE AND THE PSYCHOLOGICAL RESEARCH ON SPEECH WHICH IS NEW. YOU RAISED THE EXAMPLE OF RESEARCH THAT MAY LEAD TO FIRST EXAMPLES IS TO DECODE THE ARTICULATORY MOTOR ACTIVITY WHICH COULD BE MAPPED ON TO PHO PHONE -- PHONIC USES AND THE IDEA IS TO HAVE MADE GOOD PROGRESS AT THE END OF THE FIVE YEARS. I DON'T THINK IT'S IN THE NEAR TERM. I THINK THIS IS THE SORT OF TOOL THAT HAS PATIENTS WITH VARIOUS TYPES OF APHASIA TO DISCUSS IN TREATMENT AND DISCUSSONS UP TO NOW. AND THERE'S A DIFFERENCE IN WHAT IS GOING ON IN THE BRAIN AND THE EXPRESSED OUT AND THE NEED TO CONCEPTUAL LIKE A THOUGHT. WE THINK OF SPEECH ACTS AND WHEN PATIENTS MIGHT USE LETTER BOARDS. THAT'S A MOTOR ACT. AND THERE'S A THOUGHT BETWEEN THOUGHT AND ACTION IS REDUCED EVEN FURTHER TO THE POINT THAT BASICALLY IT SUBSTANTIATES THE RIGHT BRAIN ACTIVITY TO ENABLE THE BCI TO DECODE THE SPEECH. SO I THINK THERE ARE PARALLELS CERTAINLY WITH USING LETTER BOARDS AND SPELLERS FOR APHASIC PATIENTS BUT THERE'S A NEW CHALLENGE WITH THE MECHANISM OF A NEUROPROSTHETIC THAT ISN'T THE CASE WITH SPELLING DEVICES. >> >> Question: I WANTED TO RAISE TWO COMMENTS. THE PANEL IS WONDERFUL. THE THERAPEUTIC MISCONCEPTION AT THE BEGINNING YOU HAVE TO DECIDE WHAT YOU THINK THE INTERVENTION MIGHT DO. SO IN THE CASE OF DEPRESSION DO YOU WANT TO FEEL MORE POSITIVE, KIND OF GET RID OF ANHIDONIA OR THE MENTAL PAIN. IF YOU GO WITH THE MENTAL PAIN ONCE THAT'S GONE YOU WANT TO BE POSITIVE. AND THE BIOLOGY WOULD CHANGE. LIKE THE ARGUMENT ABOUT IT'S A STAGED OR ITERATIVE THING AND YOU DON'T KNOW WHAT YOU WANT UNTIL YOU ACTUALLY GET SOMETHING. THEN ACTUALLY WHAT YOU WANT FROM A THERAPEUTIC MISCONCEPTION WHICH IS PART OF GETTING BETTER. THAT'S ONE QUESTION. THE OTHER IS A THING THAT KIND OF SCARES ME ABOUT WHAT YOU'RE HOPING TO GET FROM A THERAPEUTIC THING. IF YOU HAVE OCD AND CONSTANTLY HAVE EMERGENT THOUGHTS THAT POP INTO YOUR HEAD AND WOULD LIKE READ AND TURN IT OFF OR YOU HAVE TOURETTES AND HAVE SOCIALLY INAPPROPRIATE THINGS HAPPEN DO YOU WANT TO STOP THE OUTPUT AND MAKE SURE NO ONE ELSE HEARS IT OR EXPERIENCES IT? YOU WANT TO TURN OFF THE THOUGHT IN THE PERSON'S HEAD. THAT CAN BE TURNED TO SOMEONE WITHOUT THE PROBLEM. SAY YOU CAN FIGURE THAT OUT. FOR THAT INDICATION THAT'S WHAT I WANT -- I DO WANT TO READ THAT BAD THOUGHT BUT BUT YOU DON'T WANT ME TO READ YOUR BAD THOUGHT. IF SOMEONE COULD READ MY THOUGHTS I'D LIKE TO KNOW ABOUT. HOW DOES THE TECHNOLOGY YOU PLAN IT FOR GOOD AND EVERYBODY STARTS TO WORRY ABOUT THE WORST-CASE SCENARIO. THOUGH THE INTENT OF THE INVESTIGATION IS SOMEHOW EVIL WHEN IN FACT THE INTENT IS FOR GOOD AND WE END UP HAVING TO CLEAN UP IS YOU DIDN'T EXPECT WHAT WAS GOING TO HAPPEN LATER. >> I'LL MAKE A RESPONSE. THAT MAY BE TANGENTIAL BUT PROMPTED BY YOUR COMMENTS. IN PSYCHIATRIC CONDITIONS PATIENTS OFTEN IDENTIFY IN SOME RESPECT WITH THEIR PROBLEMS SOMETIMES. THERE'S A STORY ABOUT A PATIENT WITH A TOURETTE PATIENT AND A DRUMMER AND PING-PONG PLAYER. HIS TOURETTE WAS HELPFUL IN THOSE THINGS HE LIKED TO DO BUT MADE HIS LIFE MISERABLE AT THE WORKPLACE. THEY WORKED OUT AN ARRANGEMENT WHERE HE'D GO OFF ON THE WEEKENDS. I THINK WHAT'S POSITIVE AND NEGATIVE IN ITS AMELIORATION IS AN INTERESTING QUESTION. WHAT'S PERTINENT TO INFORMED CONSENT IS HOW WE PRESENT THE TECHNOLOGY AND WHAT IT WILL DO TO THE PATIENT OF COURSE. AND THE VOYEURISTIC POTENTIAL AS I IMAGINE PATIENTS MIGHT HAVE IT, WOULD BE AN EXAGGERATION. IT WOULD BE A CARICATURE VERSION OF WHAT THE DEVICE WILL DO AND HOW IT WILL ACTUALLY WORK. WHAT WE'LL NEED TO DO IS THE REGULATORY ASPECT WE'RE ABLE TO DO WHEN WE DECIDE WHEN TO SPEAK, HOW TO SPEAK OR TO STOP OURSELVES SPEAKING ARE AS MUCH AS POSSIBLE THERE AS WELL IN THE NEUROPROSTHESIS OF SPEECH. WE WOULD LOOK AT WHAT'S IMPORTANT IN REGULATING NATURAL SPEECH AND GIVES PEOPLE CONTROL TO A LARGE EXTENT OVER WHAT THEY SAY. WE ALL HAVE INSTANCES WHERE WE SAY THINGS AND ARE SURPRISED WE SAID THEM AND SO ON. WHEN WE LOOK AT SUFFICIENT CONTROL IN NORMAL SPEECH WE TRY TO REPLICATE THAT AND THAT THE THE FIRST PART IN ENGINEERING THE DEVICES IN THE OPTIMAL WAY. IF THERE ARERESIDUAL CONCERNS ON CONTROLLING THE SPEECH SUCH AS THEY HAVE THIS FEAR EVERYTHING IN THEIR HEAD WILL BE REVEALED THEN THAT NEEDS TO BE COMMUNICATED AND DISCUSSED WITH THE PATIENT. IT MAY BE AS SIMPLE AS AN ON/OFF BUTTON SO THERE CAN BE ULTIMATE CONTROL THOUGH IF THE PATIENT IS LOCKED IN THERE'S A REAL QUESTION HOW THAT CAN BE BUILT IN AS A FUNCTIONALITY. I THINK -- I WOULDN'T WANT CONCERNS PEOPLE HAVE OVER THE HUGE BENEFITS PATIENTS COULD RECEIVE FROM HAVING A DEVICE THAT ENABLES THEM TO COMMUNICATE WITH PEOPLE AND TO EXPRESS THEMSLVES. BUT THAT COULD BE A QUESTION ON RECREATE THE SYSTEMS OF CONTROL WE NORMALLY HAVE OVER SPEECH AND ANY RESIDUAL GAPS NEED TO BE CAREFULLY EXPLAINED TO THE PATIENT BUT I DON'T THINK THE BENEFITS OF THE DEVICE SHOULD BE OVERSHADOWED BY THIS CONCERN AND IT ALSO SHOULD BE THE RESEARCHERS JOB TO NOT OVERSTATE THIS CONCERN INSOFAR AS THERE'S WAYS TO ADDRESS IT. >> THERE'S AN INTERESTING CONNECTION HERE. >> THIS IMPLICATES PEOPLE'S VALUES AND WILLINGNESS TO TRADE OFF IN COMMUNICATION AND MOTOR DEVICES. IF I'M THE TYPE OF PERSON THAT ALWAYS WANTS TO SAY THE RIGHT THING AND NEVER MAKE A MISTAKE I MAY WANT A DEVICE THAT TALKS MUCH MORE SLOWLY AND UNFORTUNATELY WITH THAT IN QUOTES. WHEREAS IF I'M THE PERSON THAT JUST WANTS TO GET MY THOUGHTS OUT AND I'M OKAY WITH ERRORS AND WE ALL EXPERIENCED THIS WITH USE OF TEXTING. SOME PEOPLE ARE MORTIFIED WHEN THE PHONE AUTO CORRECTS AND SIMILAR WITH MOTOR DEVICES. >> I WANT TO SHARE EXPERIENCES. I WAS PART OF THE BROADEN STUDY AND WE RECRUITED 125 PATIENTS. ONE OF THE IMPORTANT PARTS GOOD INFORMED CONSENT. WE WANTED TO MAKE SURE PATIENTS UNDERSTAND WHAT THEY WERE DOING AND WE HAD THEM GO THROUGH A PSYCHIATRIST AND CASE WORKER AND NEUROSURGEON. AFTER THEY WENT THROUGH THE PROCESS FOR INFORMED CONSENT I LEARNED ONE OF THE PATIENTS DIDN'T REALIZE THEY WERE GETTING BRAIN SURGERY. I WAS SHOCKED. WE HAD THE MODEL OUT AND THEY DIDN'T KNOW WE WERE GOING TO DRILL THEIR HEAD. WE HAVE A VIDEO AND THE 15-PAGE CONSENT WAS READ AND WENT OVER WITH WITH THE PATIENTS BUT WE WANTED TO MAKE SURE THEY HAVE THE VISUAL. SOME PEOPLE AREN'T READING. THEY HAD VISUAL LEARNING OF TAKING THEM THROUGH THE STUDY ITSELF. THAT'S SOMETHING TO BASICALLY CONSIDER OF OTHER WAYS. IN ANOTHER PIECE WE DID AS WELL AT ONE CENTER WE VIDEO TAPED THE INFORMED CONSENT PROCESS SO THE PATIENT KNEW PRIOR TO SURGERY THEY KNEW WHAT THEY WERE CONSENTING TO AND ASKED THE VARIOUS QUESTIONS. >> ONE THING I LEFT OUT OF MY PRESENTATION, ALL THE INDIVIDUALS WHO TALKED ABOUT THEIR LACK OF UNDERSTANDING AND APPRECIATION IS ALL RETROSPECTIVE. NOT ONE PERSON FAULTED THE STUDY FOR A BAD CONSENT PROCESS OR FAULTED THE INVESTIGATORS. THEY WERE LOCATING THE PROBLEM WITH THEMSELVES AND THE STATE OF THEIR DISEASE. IT'S IMPORTANT INFORMATION I LEFT OUT. >> IF YOU FIND SOMEBODY HAVING BRAIN SURGERY DOESN'T REALIZE IT IT'S GOOD TO HAVE AN EFFECTIVE METHOD TO REINFORCE THE BASIC POINT ON WHAT THE PROCEDURES ARE AND WHAT THE RISKS ARE. AND RELATED TO ERIN'S POINT, WHAT YOU NEED IN THE DISCLOSURE PROCESS AND WHAT YOU HAVE TO ENFORCE IN UNDERSTANDING AND ONE RESPECT FOR PERSONS IS TO ACKNOWLEDGE THEY HAVE SOME RESPONSIBILITY FOR THEIR OWN CONSENT. GOOD >> >> ON THE THEME OF COMPREHENSION AND CONSENT. WE SPOKE TO 150 SUBJECTS WHO WENT THROUGH TRIALS FOR PARKINSON'S DISEASE. I THINK IF I HAD TO SUMMARIZE WHAT WE LEARNED BECAUSE OUR STUDY WAS NOT A FORM THEY FILLED OUT. WE SPENT AN HOUR ON THE PHONE WITH A PRESET SO IT WAS AN HOUR'S WORTH OF CONVERSATION. AND IF WE HAD THE CONVERSATION WE'D SOUND THE SAME. WHAT'S THAT MEAN? WE'D TALK ABOUT THE KINDS OF THINGS THEY WERE MOTIVATED BY. IF YOU ASKED THEM OUT OF SENSE OF ALARM BECAUSE THEY THOUGHT THEY'D REALLY BENEFIT WELL, IF YOU PROBE AND TALK ABOUT IT YOU SEE HOW THEY UNDERSTAND THE QUESTION. THE DEEPER CONTEXT COMES OUT. THE THING I'M TRYING TO POINT OUT IS THAT PEOPLE HAVE LOTS OF MOTIVATIONS AND PEOPLE HAVE DIFFERENT VIEWS ABOUT WHAT'S IMPORTANT WHEN YOU SIT DOWN AND TELL THEM ABOUT A VERY COMPLICATED STUDY. IT'S THE RARE PERSON WHO ACTUALLY IGNORES KEY THINGS LIKE -- OUT OF 120 PEOPLE WE ONLY HAD ONE PERSON WHO MET THE CLASSIC CONCEPTION OF THERAPEUTIC MISCONCEPTION AND I PUBLISHED THIS SO YOU CAN FIND IT. THEY SAID IT WASN'T UNTIL HALFWAY THROUGH IT IT BEGAN TO DAWN ON ME WHAT THEY WANTED TO DO WAS TEST THIS THING AND IT WASN'T FOR ME. THAT WAS ONE PERSON OF 120. WE REALLY HAVE TO UNDERSTAND THE FRAMEWORKS, VOCABULARY AND TENDENCY TO LOOK AT THE PROBLEM FROM THE PERSPECTIVE OF THE DISCUSSION AND CONSIDER HOW MUCH OF OUR CONVERSATION, WHAT WE FIND OUT FROM THE PATIENTS WHEN WE HAD THE DISCUSSION IS AS MUCH AS THE FRAMEWORK WE BRING TO THE CONVERSATION AND THE CONTEXT OF THE DISCUSSION. I'D LIKE TO USE THE SPORTS ANALOGY THE BEST. PEOPLE -- WE'RE ALLOWED TO SAY COMPLETELY CONTRADICTORY THINGS. FOR EXAMPLE, WHEN I SAY, I THINK THERE SAY REALLY GOOD CHANCE AND IT SOUNDS LIKE A PROBABILITY STATEMENT, WE'LL PULL OFF THE UPSET. THEY GO IN DIFFERENT DIRECTIONS. WE HAVE TO UNDERSTAND WE CAN'T HOLD PEOPLE TO ARTIFICIAL RULES OF RATIONALITY WHEN WE TALK TO PATIENTS AND RESEARCH SUBJECTS. WE HAVE TO REALLY UNDERSTAND WHERE THEY'RE AT. IF WE CAN SAY AS THE A GREAT CHANCE OF PULLING OFF AN UPSET EITHER THERE'S A LOW PROBABILITY OF THAT HAPPENING, WE NEED TO UNDERSTAND HOW WE APPROACH THE SITUATION. >> I DON'T KNOW IF THIS MAKES SENSE BUT YOU TALKED ABOUT DESPERATE PATIENTS. I WAS STRUCK BY SOME OF THE QUOTES AND I KNOW YOU PUT THE CAVEAT ON WHAT ERIN HAD. PEOPLE SAID THIS IS THE ONLY HOPE I HAD. IN SOME CASES IT'S TRUE BUT THEN IF THEY SAY IN THE SAME SENTENCE I DON'T CARE ABOUT THE RISKS OR ANYTHING AND SHOULD WE CARE ABOUT THEM IN THIS SPACE, WITH THESE DEVICES THAN OTHER SPACES AND WE RUN INTO PEOPLE IN CHEMOTHERAPY TRIALS AND A SECOND QUESTION -- IT JUST OCCURRED TO ME, SHOULD WE TOLERATE ANY KIND OF THERAPEUTIC MISCONCEPTION FROM A SURROGATE DECISION MAKER THAN FROM THE MAIN PERSON THAT WE'RE ENROLLING? >> IN RESPONSE TO THE LAST QUESTION, I DON'T KNOW. THE SURROGATE IS ALWAYS AT LEAST ONE REMOVED FROM THE SUBJECT. I MIGHT HAVE MORE CONCERN BUT AT THE SAME TIME I'D LIKE TO THINK ABOUT IT MORE. >> IT TURNS OUT THESE ARE STUDIES THAT ARE SPECIALIZED CENTERS. YOU HAVE A MIXTURE OF PEOPLE THAT ARE LOC RECRUITED BY THEIR OWN DOCTORS WHO WERE SITE P.I.s AND PEOPLE WHO RESPONDED TO ADVERTISEMENTS AND THEN FLEW TO DIFFERENT LOCATIONS TO BE IN THE STUDY. WHAT'S INTERESTING IS THEY HAD DIFFERENT TYPES OF RESPONSES. THEY WERE TWO TYPES OF PEOPLE. YOU WOULD THINK PEOPLE ENGAGED BY THEIR OWN DOCTORS WOULD BE MOST CONCERNED ABOUT THE THERAPEUTIC MISCONCEPTION. THE RESEARCHER AND DOCTOR BOTH WEAR WHITE COATS. WE FOUND THE OPPOSITE. IT'S THE PEOPLE WHO SEEK OUT THE TRIALS WHO LOOK AT IT FROM A RISK BENEFIT. THIS CAN HELP ME. THE PATIENTS WEREN'T LOOKING FOR IT. THEIR DOCTOR TELLS THEM SO THEY'RE LESS LIKELY TO SEE THIS IN TERM OF RISK BENEFIT AND TEND TO BE MORE, QUOTE, MIXED MOTIVE OR OR ALTRUISTIC. IT DOESN'T ALWAYS TURN OUT THE WAY WE EXPECT. >> ON THE POINT OF BEING DESPERATE, WE NEED TO MAKE A COMPARISON TO THE CLINICAL SITUATION. SOMEONE FACING A LIFE-THREATENING ILLNESS AND WE HAVE TO ASK OURSELVES WHAT'S DIFFERENT ABOUT THE RESEARCH CONTEXT IN TERMS OF VOLUNTARINESS AND VALID CONSENT THAT WOULD INDICATE WE SHOULD BE MORE CONCERNED BECAUSE THERE'S SITUATIONS WHERE THE PATIENT WITH METASTATIC CANCER AND PHASE 1 TRIAL IS YOUR ONLY OPTION YOU MAY BE DESPERATE BUT I DON'T SEE HOW THAT'S DIFFERENT THAN THE CLINICAL SITUATION. >> I THINK -- I WOULD SAY IT'S NOT NECESSARY TO MAKE SUCH A DISTINCTION. THERE'S ARE SURGICAL PROCEDURES BUT COUPLE ISSUES ON WHAT'S THE RISK OF NOT DOING SOMETHING AND IT'S NOT AS OBVIOUS AS CANCER WHERE IT'S LIKELY AND SOMEONE WITH SEVERE DEPRESSION IS AT RISK FOR THEIR LIFE AS WELL AND SOMEONE WITH TERRIBLE OCD IS LIVING A SHATTERED LIFE AND INFLUENCING THOSE AROUND THEM AS WELL. WE'RE TALKING ABOUT PROCEDURES THAT CAN BE DONE RATHER SAFELY. WITH INFORMED CONSENT AND COERCION AND I'LL FLIP BACK TO THE GROUP ON HOW DO YOU DO THAT PROCESS AND WHAT'S THE PRACTICAL ASPECTS OF INFORMED CONSENT AND TRYING TO AVOID COERCION. IF THE INVESTIGATOR IS THE CLIN CLINICIAN AND SURGEON I'M HAPPY I'M NOT THIS AT THE DISCUSSION. I FEEL LIKE I'M NOT COERCING THE THE POINT I WANT TO BRING UP IS THAT I DON'T KNOW IF THAT'S ALWAYS THE RIGHT THING. DON'T WE HAVE THE RESPONSIBILITY TO MAKE SURE THAT PATIENT IS GETTING THE INFORMATION AS PRECISELY AS WE CALLED AND IF THE STUDY IS PART OF A SURGICAL PROCEDURE, DIDN'T THE PERSON DOING IT MAYBE THEY SHOULD BE THERE BECAUSE THE QUESTIONS MAY BE INTERRELATED. SO MAYBE I'VE BEEN DOING IT THE WRONG WAY WOULD I BE WRONG TO BE THERE. WHAT DO PEOPLE THINK ABOUT THE CLINICIAN BEING THERE FOR THE IN BETWEEN QUESTIONS AND ARE WE DOING THE BEST TO DO THE STUDY APPROPRIATELY. >> I THINK FOR WHEN RESEARCH IS DONE THERE'S LIKELY QUESTIONS THAT ARE TECHNICAL AND SURGICAL IN NATURE. I'LL SPEAK ON THE BEHALF OF THOSE I WORK WITH YOU MAY NOT HAVE THE ANSWERS MOST RELEVANT TO PATIENT'S PARTICIPATION. THE TWO THINGS I WOULD SAY IS I DON'T THINK THERE'S A UNIVERSAL RULE ON WHO SHOULD OBTAIN CONSENT AND IN EITHER CASE ADDITIONAL PROTECTS ARE NECESSARY. IF THE INVESTIGATOR OR RESEARCHER ARE OBTAINING CONSENT THERE'S ISSUES OF UNDUE INFLUENCE OR A MEMBER OF THE RESEARCH TEAM OBTAINING CONSENT, ONE THING WE FOUND IS A LOT OF THOSE POST-DOCS DON'T FEEL THEY HAVE THE CLINICAL EXPERTISE PATIENTS OFTEN HAVE. AND IT'S A MATTER OF TRYING TO MAKE SURE WHATEVER SYSTEM HAVE YOU IN YOUR CENTER YOU'RE ATTENTIVE. >> I'LL START FROM WHERE YOU START SOMETHING AND THERE'S INTELLECTUAL PROPERTY AND THERE'S RELEVANT DISCUSSION WHERE IT GOES FROM A PILOT TO AN EXPERIMENTAL TRIAL TO OTHER PEOPLE DOING IT AND RESEARCH WITH MANY LAYERS. I'M NO LONGER ALLOWED TO DO INFORMED CONSENT. I'M NOT ALLOWED TO VETO ANY DISCUSSION ON ANY PATIENT NOR TO RATE THEM OR DECIDE IF IT'S WORKING OR NOT. PATIENTS COME TO EMERY BECAUSE YOU HAVE TO DO EXPERIMENTS OVER TIME. WE WISH WE HAD MORE PATIENTS LOCALLY. IT WOULD BE EASIER. AND THERE ARE SOME THERE. WE HAVE LOCAL PATIENTS THE PSYCHIATRISTS KNOW AND PATIENTS THAT COME AND MOVE TO ATLANTA TO BE IN THE SEVEN-MONTH STUDY. FIRST YOU HAVE TO GET RID OF THE THERAPEUTIC OR I'D LOVE IF SOMEBODY STUDIED THE THERAPEUTIC MISCONCEPTION OF THE PSYCHIATRIST. THAT'S AN ISSUE FOR PEOPLE IN CLINICAL TRIALS. I FOUND THERE'S TWO DAYS PROCESS FOR THE INFORMED CONSENT AND THEN SEE THE SURGEONS WHO EXPLAIN EVERYTHING. I NEVER MEET PATIENTS UNTIL THOSE THINGS ARE DONE AND I ALWAYS HAVE TO BE THE ONE TO COME IN AND REFRAME THE EXPERIMENTAL NATURE OF WHAT WE'RE GO TO DO AND THE PATIENTS HAVE AN INSPECTION OF EXPECTING TO HEAR FROM THE SCIENTIFIC LEADER OF A STUDY AS TO WHAT IT IS BECAUSE PART OF WHY THEY COME IN HAS SOMETHING -- AND I'M SURE AT UCSF THEY COME IN -- THE EXPERTISE OF THE LEADER -- I'M NOT CLAIMING ANY PARTICULAR POWER BUT THERE IS THE ILLUSION THAT I MUST KNOW SOMETHING BECAUSE I DID SOMETHING AND HOW YOU FRAME THE SCIENTIFIC EQUIPOISE. HERE'S WHAT WE'LL DO AND HOW PEOPLE WILL PROTECT YOU AND WHY YOU'RE HERE. WHEN THEY NEGOTIATE ABOUT I DON'T WANT TO DO THIS OR GET IN THE THERAPEUTIC MISCONCEPTION IT BECOMES THIS IS AN EXPERIMENT AND THIS IS WHAT GOES ON. IT'S NOT A GOOD COP/BAD COP IT'S DIFFERENT MEMBERS OF A TEAM SERVE DIFFERENT ROLES TO REINFORCE THE DIFFERENT ASPECTS OF WHAT THE TRIAL IS AND IT'S DIFFERENT WHAT EVERYONE GETS OUT OF IT. >> IN REALITY BY IT TIME PEOPLE TALK TO THE SURGEON PI OF A STUDY THAT INVOLVES THIS LEVEL OF IN VASE -- INVASIVENESS THEY THEY'LL GO IN THE STUDY AND IT'S INFORMING TO A PERSON WHO HAS ALREADY PRETTY MUCH -- THEIR APPROACH IS ARE THERE RED FLAGS. I THINK THE MULTIPLE APPROACHES OF SURGEON AND PI IS IMPORTANT. I KNOW THIS SOUNDS TERRIBLE AND I DON'T WANT TO STEREOTYPE SURGEONS BUT WHEN YOU TALK TO PEOPLE THEY REMEMBER THE CONVERSATIONS WITH SURGEONS. WHEREAS YOU HAVE TO PROBE THEM TO GET THAT CONVERSATION WITH THE NEUROLOGIST. THE APPROACH AND PRESENCE AND CONFIDENCE WHEN YOU DELIVER THE PROS AND CONS THEY EXPERIENCES IT DIFFERENTLY. LOOK, IF I'M SEEING A DOCTOR AND THEY'RE GOING TO MY BRAIN I DON'T WANT THEM TO SEEM TENTATIVE OR WHATEVER. MULTIPLE PERSPECTIVES HAVE DIFFERENT EFFECTS ON PEOPLE. >> THIS IS MORE OF A QUESTION THAN SUGGESTION. MAYBE WE SHOULD THINK OF TRYING TO MODIFY THE TRIAL TO MAKE IT POSSIBLE TO DO GOOD INFORMED COULD BE SENT. I THOUGHT OF THAT -- GOOD INFORMED CONSENT. I WAS THINKING ABOUT HANNAH'S STORY. WE DON'T KNOW WHAT WE'LL BE ABLE TO PULL OUT OF THE SPEECH. YOU KEPT TALKING ABOUT IT AS AN ENGINEERING PROBLEMS WHICH IMPLICITLY SAYS IT'S A PROBLEM PEOPLE WILL BE ABLE TO FIX BUT WE DON'T REALLY KNOW THAT BEFORE WE START DOING IT. IT'S HARD TO GIVE INFORMED CONSENT WHEN YOU'RE AT SUCH LEVEL OF IGNORANCE. MAYBE YOU DO A FIRST TRIAL WITH THE FIRST PEOPLE WHERE YOU DON'T KNOW ANYTHING AND GIVE STRONG CONSENT AND A SECOND TRIAL YOU CAN GIVE A MORE SPECIFIC AND LIMITED CONSENT. SO IN A WAY IT'S PHASING TRIALS IN PART OF WHAT YOU CAN TELL THE POTENTIAL SUBJECTS IN THE CONSENT. I DON'T KNOW HOW USEFUL THAT IS BUT IT CAME TO MY BRAIN AND I COULDN'T KEEP IT FROM COMING OUT OF MY SPEECH. >> I THINK THAT'S AN INTERESTING SUGGESTION. JUST TO CLARIFY, I DON'T THINK IT'S ONLY AN ENGINEERING QUESTION WHAT WE CAN PULL FROM DIFFERENT AREAS OF THE BRAIN. THAT'S A QUESTION FOR NEUROSCIENTISTS FIRST AND FOREMOST AND THEY'LL HAVE HYPOTHESES ON WHAT THEY CAN EXTRACT BUT THE ENGINEERING QUESTIONS COMES IN THE BRAIN INTERFACE AND SYNTHESIZING THE SPEECH. IT'S A COLLABORATIVE PROBLEM BUT I DIDN'T MEAN TO SAY IT'S ONLY APE AN ENGINEERING PROBLEM BUT IT'S AN INTERESTING THOUGHT TO PHASE THE TRIALS ACCORDING TO HOW MUCH WE CAN CONFIDENTLY PREDICT WHAT WE'LL BE ABLE TO PULL FROM THE BRAIN FROM A PARTICULAR REGION. IT WILL MATCH RESEARCH WHERE WE MIGHT GET SOMETHING FROM THIS AREA AND THEN GET A PROOF OF PRINCIPLE ANDDECODE THE STRATEGIES. IT'S A GREAT SUGGESTION. >> I'D LIKE TO THANK THE PANEL FOR WONDERFUL PRESENTATIONS AND GREAT DISCUSSION. I'M ONE OF THE DIVISION MEMBERS AND IT'S MY PLEASURE TO SERVE AS LOT -- MODERATOR OF THE LAST PANEL. THE TOPIC IS POST-TRIAL RESPONSIBILITIES. THE SPEAKERS WERE ASKED TO ADDRESS QUESTIONS SUCH AS CONSIDERING OF PLANNING FOR THE DEVICE AND RELATED NEEDS AFTER THE STUDY IS OVER. WHEN THE STUDY TEAM'S RESPONSIBILITIES END. WHICH PARTIES ARE RESPONSIBLE FOR FINANCIAL CONCERNS AND COST RELATED TO REMOVING A DEVICE. WE HAVE A FRAMING SESSION FOR 20 MINUTES LED BY HELEN MAYBERG AND THE PANELISTS WILL GET 20 MINUTES AND I HAVE AN OBNOXIOUS ALARM AND I'VE TOLD MY SPEAKERS AND I GESTICULATE WILDLY WHEN IT CLOSE TO THE TIME OF YOUR COMPLETION. FIRST IS HEALEN MAYBERG CURRENTLY IN THE DEPARTMENT OF RADIOLOGY AND NEUROPSYCHIATRY. PLEASE GET STARTED. >> MY COLLEAGUES THAT WILL HAVE AN INTERESTING POINT ON THE TOPIC. I'M FRAME THIS FROM THE POINT OF VIEW OF THE LAST 13 YEARS IN DOING WHAT I THOUGHT WAS AN INTERESTING NEUROSCIENCE EXPERIMENT AND TAKING CARE OF PATIENTS WHO CONTINUE LONG-TERM WITH IMPLANTED DEVICES UNDER 90E AND IN THE CONTEXT OF THE QUOTE, UNQUOTE FAILED BROADEN STUDY WHICH EXTENDED. AND WE'LL TALK ABOUT THAT AS WELL. I HAVE DISCLOSURES WITH A BUNCH OF ETHICISTS. THE GRANT IS SUPPORTED AND NOW WE HAVE A UH3 OFF LABEL-USE DEVICES AND THE WORK HAS A PATENT AND LICENSED TO ST. JUDE MEDICAL THAT TOOK IT TO A CLINICAL TRIAL. SO WE HAVE THAT ENTIRE EXPERIENCE I WANT TO TALK ABOUT. I'LL TALK ABOUT DEPRESSION AND LET'S FRAME HOW BIG IS THIS PROBLEM. AS WE THINK ABOUT THE BRAIN INITIATIVE AND SEEN THE A.D. PROJECTS. I LOOKED AT ALL OF THEM, MANY OF THEM ARE REALLY ABOUT TOOL DEVELOPMENT, MEASURANCE MEASURENCE IN HUMANS AND DEVICES YOU'D REMOVE. WHAT WE'LL BE TALKING ABOUT IS WHAT HAPPENS AFTER CHRONIC TREATMENT SO IT'S A DIFFERENT SET OF ISSUES. . WE WANT TO LOOK AT THE CHART IN THE CONTEXT OF COMMERCIALIZATION OR FDA APPROVAL. WE ARE DOING EXPERIMENTS WITH DEVICES BECAUSE WE WANT THEM TO HAVE LONG TERM. THIS IS NOT A CAST AND YOU TAKE IT OFF AND GO AND YOUR WAY WE IMAGINE THIS WOULD BE A CHRONIC TREATMENT. IF HAVE YOU FDA APPROVAL AND YOUR TRIAL WENT WELL AND YOUR A PATIENT THAT HAD A GOOD OUTCOME AND HAPPY AND MOVE FORWARD. EVEN IF THERE WAS FDA APPROVAL AND YOU PERSONALLY HAD A BAD OUTCOME, WELL, YOU'RE DISAPPOINTED BUT THAT'S WHAT PRECISION MEDICINE IS ABOUT. IF WE DON'T LEARN BIOLOGICALLY WHAT TO GET PEOPLE THERE'S PEOPLE WE'LL GET WHERE WE CAN NEVER EXPECT 100% RESPONSE. IF THERE'S NOT FDA APPROVAL THE BLM BOTTOM LINE DISCUSSION IS. IF YOU DID GREAT AND FRANKLY YOU'RE CONCERNED AND CONCERNED AND CONFUSED BECAUSE IT'S LIKE, WELL, I'M DOING WELL. AM WHAT I GOING TO DO. AND IF YOU THINK YOU'LL NEVER GET BETTER ON ANYTHING AND THE NIALIST PART OF THE DISEASE SHINES THROUGH. THEN WITH THE FOUR BOX YOU LOOK AT YOUR POST-TRIAL OPTIONS. WELL, YOU NEED A WAY TO KEEP IT WORKING AND IF IT BREAKS ANYONE SO FIX IT AND THAT THE GOLD STANDARD OF CARE. AND POST HAD-TRIAL CARE IS IF YOU HAVE INSURANCE MAYBE IT WAS PAID FOR BY THE DEVICE COMPANY BUT STANDARD OF CARE YOU'RE ASSUMING RESPONSIBILITY NOW FOR YOUR CARE BECAUSE IT'S NOW IN THE COMMERCIAL PLACE AND MAYBE IT'S MEDICARE AND WHAT DO YOU DO IF YOU DON'T HAVE INSURANCE SO SELF-PAY. KEEP THIS IN MIND AND IT'S SO IN WEEDS. I LIKE TO THE NEUROSCIENCE OF ALL OF THIS BUT IT'S THE REAL NITTY-GRITTY WHEN YOU PLAY FOR A LIVING AND THEN IT BECOMES REAL PATIENTS WITH THESE ISSUES WHAT ARE OUR OPTIONS. IF IT'S NOT SUPPORTED AND JUST NOT AVAILABLE IT'S JUST LIKE TOUGH LUCK. SAD. IF IT'S IN THE USE OF AN APPROVED DEVICE AND THE DEVICE IS AVAILABLE YOU CAN ASK IF YOU GET WELL AND IT'S ONLY FAIR AND YOU ALL HAVE THE REAL WORD IN LATIN TO DESCRIBE THAT. THEN WE HAVE THE PEOPLE WHO DID BADLY AND IT'S NOT AVAILABLE AND THE OBVIOUS WOULD BE TAKE IT OUT. TO THE ISSUE IN GOOD FATHER AND SHOULD I HAVE TO PAY TO THE ISSUE OF IN GOOD FAITH SHOULD I HAVE TO PAY FOR THE RIGHT TO MY NEXT OPTION. I THINK THE OFF-ANGLE LABEL IS WHO PAYS, WHO PAYS FOR WHAT AND AFTER HOW LONG IF YOU'VE BEEN IN A TRIAL SHOULD SOMEONE BE WILLING TO DO SOMETHING AND AGAIN IT'S THE PATIENTS, INSURANCE, THE SPONSOR. I WILL SAY THAT THE BROADENED STUDY CAN SPEAK MORE THAT WHEN THE TRIAL WAS STOPPED AND I'LL GET TO THAT IN A MINUTE. I'LL JUST WAIT AND DO IT IN CONTEXT. SO WHAT'S THE SCOPE OF THE PROBLEM TO ANSWER MIKE'S QUESTION IN DEPRESSION. HOW MANY PATIENTS ARE IMPACTED BY THE SCENARIO BECAUSE THERE WAS THE CLAIMS STUDY THAT MED TRONICS SPONSORED AND THEN WAS HALTED AND THERE'S AREA 25 TARGET, THE BROADEN THAT pIMPLANTED 34 IN ATLANTA.E HAVE THAT WAS ANOTHER 40 OR MORE IN TORONTO AND IT'S A STUDY IN BERLIN AND IN CALGARY. THERE'S ESTIMATES THAT ARE APPROACHING 200 IN AND SMATTERINGS IN THE MEDIAL FOREBRAIN BUNDLE. AND I CAN FIND CASES OF PEOPLE THAT HAVE BEEN IMPLANTED ON SOME KIND OF STUDY. YOU CAN SEE THE BREAKOUT. SO THERE ARE A NUMBER OF PEOPLE AFFECTED. WHEN THINK ABOUT THE BRAIN INITIATIVE AND YOU'RE PROPOSING FIVE AND MAYBE A FOLLOW UP WITH ANOTHER FIVE. AND AS A SPONSOR IT IS MY RESPONSIBILITY AND I HAVE TO DEAL WITH SOMETHING DIFFERENTLY THAN A DEVICE COMPANY WOULD. I TALK ABOUT IT PERSONALLY BECAUSE I THINK ANYONE WITH A BRAIN INITIATIVE GRANT AND PI AND HAS TO FILED THEIR OWN IDE HAS TO KEEP THAT IN MIND AND I HAVING HAD MY OWN IDEs ON THESE TOPICS SINCE 2008. SO IN THE BROADEN STUDY THIS WITH US JUST PUBLISHED ON THE 90 PATIENTS. THEY WERE ASKED TO DO UTILITY ANALYSIS AND HALFWAY MARK WAS AT THE PROJECTED 200 PATIENTS ENROLLED. ACTIVE DID NOT BEAT SHAM ON THE PRESCRIBED 40% RESPONDER, 20% SHAM. IT WAS 20% RESPONDER WITH 60% ON SHAM. THE PROBABILITY OF REACHING THEIR PREDEFINED END POINTS WAS 17% AND THE COMPANY FELT THAT WAS NOT GOOD ODDS IN CONTEXT OF NEW SCIENCE COMING OR FINANCIAL. THERE WAS SHAM CONTROL AND IT WAS STILL DOUBLE BRIELIND TO WHAT YOU WERE ON IN THE FIRST SIX MONTHS. AT THE END OF THE SIX MONTHS AND THEY ALSO THEN HAD A SECOND PART TO THE EXPERIMENT WHICH WAS PATIENTS COULD ENROLL IN LONG-TERM FOLLOW UP WHICH MEANT THEY HAD OPEN LABEL. THEY CAN CHANGE THEIR MEDS, CHANGE THE DEVICE. CHANGE THE SETTINGS, GET ADVICE BUT THEY WOULD BE FOLLOWED UP AT REGULAR INTERVALUES TO HAVE OTHER DATA COLLECTED. YOU CAN SEE WHILE THE TRIAL AT THE DEFINED SIX-MONTH END POINT WAS DEEMED A FAILURE, THERE WAS A 50% RESPONSE RATE AT 18 MONTHS MAINTAINED AT TWO YEARS. SO YOU WERE NOT HERE TO DISCUSSION WHAT WE ALL THINK IT MEANS BUT IT'S THE REALITY OF 90 PEOPLE WITH 77 THAT WENT TO LONG-TERM FOLLOW UP AND 36 PEOPLE WHO ARE NOW RESPONDING. WHAT DO YOU DO WHEN THE COMPANY DECIDES TO CLOSE THE TRIAL? THAT'S NOT A FEW PEOPLE. THAT'S A LOT OF PEOPLE. AND THE COMPANY -- AND THIS IS WHERE I THINK I DON'T KNOW WHAT TO DO. I'M JUST GOING TO KEEP TALKING BECAUSE SHE'S GOING TO HURT ME. BASICALLY YOU HAVE A GROUP OF PEOPLE WOULD ARE WELL AND SOME AREN'T AND THE COMPANY AT THE POINT TO STOP THEIR TRIAL WHICH WAS PLANNED FOR FOUR YEARS OF LONG-TERM FOLLOW-UP AND BATTERIES ARE HAVING TO BE REPLACED EVERY TWO YEARS WHAT WOULD THEY OFFER AND WHAT WILL THEY DO. WHAT THEY ETHICALLY DID WAS SAY, IF YOU'D LIKE TO CONTINUE WE WILL PAY FOR TWO IMPLANT A RECHARGEABLE BATTERY WITH A PROJECTED TEN-YEAR RESPONSE. YOU'LL NEED TO HAVE A PSYCHIATRIST. GENERALLY ONE FROM THE STUDY TEAM WHO HAS EXPERIENCE IN USING THE DEVICE AND IF YOU'RE BETTER OR DON'T WANT THE DEVICE WE'LL EXPLANT YOU. PEOPLE WERE OFFERED AN EXIT STRATEGY. I ASKED WHAT -- SINCE IT STARTED IN 2008 WHAT ARE THE NUMBERS. 38 PEOPLE ASKED TO BE EXPLANTED. FOUR PEOPLE DIED, TWO BY SUICIDE VERY EARLY IN THE TRIAL AND THAT MEANS THAT FIVE PEOPLE ARE STILL DECIDING WHAT THEY WANT TO DO. THAT BASICALLY THE REST OF THE PEOPLE THAT HAD RECHARGEABLE BATTERIES AND ARE CONTINUING ON SO THAT'S ONE SCENARIO. AND THE DATA FROM TORONTO AND ATLANTA WHERE THERE'S NOW ACTUALLY THE FIRST IMPLANT IN TORONTO WAS IN 2003. FIRST IMPLANT IN TALENT WAS 2008. AND YOU CAN SEE TORONTO ON THE LEFT AND TALENT ON THE RIGHT AND ON AVERAGE THIS IS LOOKING AT SIX-YEAR LONG-TERM FOLLOW-UP. IT'S OVER 60% RESPONSE FOR LONG TERM. IN CANADA YOU CAN IMPLANT WITHOUT AN IDE BECAUSE THERE'S NOT AN FDA TO GO TO. YOU NEED IRB APPROVAL. THE HEALTH CARE SYSTEM PAID FOR THE FIRST GROUP AND BECAUSE IT WAS EXPERIMENTAL THEY WEREN'T PAYING MORE AND THE TEAM HAS HAD MORE STANDARD RELATIONSHIP WITH INDUSTRY. THAT WAS AFTER I LEFT. AND WITH THE ST. JUDE DEVICE WAS EVERY TWO YEARS. THE OTHER DEVICE IS FOUR YEARS. YOU HAVE A DIFFERENT DEMAND TO GO BACK TO THE OPERATING ROOM BUT IF YOU'RE WELL YOU ARE FINE TO GO BACK AND NOW YOU HAVE A RECHARGEABLE DEVICE TO NOT INTEREST THE BURDEN AND WITH WHERE THEY ARE THIS MANY YEARS LATER HALF THE PATIENTS DROPPED OUT, WHICH I WAS SURPRISED TO HEAR. YOU HEAR THE GOOD ONES. THEY CONTACT YOU. SIX WERE EXPLANTED AND FIVE DIED AND FIVE WERE EXPLANTED. WE HAVE HAD TROUBLE WITH BROKEN LEAD AND INFECTION BECAUSE WE HAD DONE 10 2 BATTERY REPLACEMENTS. THE ISSUE BECOMES YOU HAVE ALL KINDS OF THINGS THAT GO ON OVER FIVE AND TEN YEARS. I HAVE TO KEEP ADDING YEARS BECAUSE I HAVE AN UNAPPROVED DEVICE AND THAT'S OUR RESPONSIBILITY. TO FINISH AND TO FRAME THE NEXT TALK IS THIS IS KIND OF MY LIST, WHO'S THE SPONSOR? YOU HAVE THE RESPONSIBILITY. IS THE DEVICE A NOVEL DEVICE YOU BUILT IN THE BASEMENT OR DID YOU REPURPOSE A COMMERCIALLY DEVICE A GOOD WAY TO GO. WHAT STAGE ARE YOU AT? WE STARTED AT A PILOT NOT A RANDOMIZED CLINICAL TRIAL. AND IF YOU TAKE CARE OF PEOPLE LONG TERM. THEY WANT YOU TO WALK THEIR DOG AND MAKE RECOMMENDATIONS FOR IF THEY GET CANCER. YOU HAVE TO BE INVOLVED AND PEOPLE BECAME AFRAID OF HAVING INVESTIGATIONAL DEVICES. YOU HAVE TO THINK ABOUT A START- START-UP COMPANY WITH A NEW DEVICE THINKING ABOUT GOING COMMERCIAL AND WHAT HAPPENS WHEN THEIR TRIAL DOESN'T WORK AND WHAT'S THE BLOW BACK? EVERYBODY LOOK UP THE CASE OF NORSTAR. LOOKING AT MOTOR PLASTICITY AND REHAB AND I'M DOING A SMALL DEPRESSION STUDY ON THE SIDE WHEN THE MOTOR STUDY DIDN'T GO WELL AND THE VENTURE CAPITALISTS PULLED THE MONEY AND THE PEOPLE NO LONGER HAD ANYONE TO SUPPORT THEIR DATA. AND THE LAST SLIDE AND WHERE DOES RESEARCH BECOME THERAPY. IT'S TO KEEP PEOPLE WELL. THEY'RE BEEN WELL FOR YEARS. IF I GET TIRED -- I'M MOVING TO NEW YORK. I HAD TO TALK TO PATIENT THE IDE WILL BE MAINTAINED. THE TEAM WILL CONTINUE TO TAKE CARE OF THEM. I'LL BE ACCESSIBLE BUT WHO STOPS TO THINK ABOUT THESE THINGS? THEY'RE ALL IMPORTANT ISSUES. I WANT TO BRING UP ITEM THREE BECAUSE IT'S COME UP OVER AND OVER HOW YOU HELP PATIENTS TO KNOW THE STAGES THEY FIRST WANT YOU TO LOOK AT THE RESULTS. YOU CAN'T ANTICIPATE. IT'S IT RATIVE. THERE'S A BIOLOGICAL AND PHILOSOPHIC PHILOSOPHICAL ARGUMENT FOR PATIENTS HAVING THE AGENCY TO HANDLE THEIR WELLNESS AND THEY HAVE TO TAKE UP THE RESPONSIBILITY BECAUSE AT THE END OF THE DAY THERE'S A FINANCIAL NEED. IT COMES DOWN TO MONEY. ONCE IT'S WORKING HOW DO YOU WORK TO HAVE PEOPLE HAVE ACCESS. THE LAST POINT IN DEFINING IF PEOPLE ARE WELL AND THEY'RE GOING TO TAKE ON RESPONSIBILITY AND WANT TO KEEP SOMETHING, HOW DO WE DEAL WITH THE IDEA OF DEFINING WELLNESS. WHAT IS IT 50% DROP ON A HAMILTON AND THAT GETS INTO A SLIPPERY SLOPE. IF SOMEONE IS WILLING TO PAY FOR IT THEMSELVES AND THEY FEEL THEY'RE GETTING BENEFIT I'M FINE WITH THAT AND THAT'S SOMETHING WE HAVE TO THINK ABOUT. IT'S NOT A SCIENTIFIC QUESTION BUT CLINICAL AND ETHICAL QUESTION. >> WE HAVE MICHAEL KELLY AT CASE WESTERN UNIVERSITY AND METRO HEALTH MEDICAL CENTER. >> GOOD AFTERNOON, EVERYONE. THANKS FOR HAVING ME. I'M A PRACTICING NEUROSURGEON WITH A BACKGROUND ON MEDICAL POLICY AND WE'VE HAD A LOT OF CONVERSATIONS WITHIN OUR PANEL BEFORE GETTING HERE AND I THINK YOU'LL SEE THE THEMES RECUR. MY INTEREST RESOLVED HOW OUR IDEAS OF RESEARCH AND CLINICAL ETHICS PLAYS OUT IN HOW TRIALS ARE STRUCTURED AND WHAT HAPPENS IN THE TRIALS. CLASSICALLY THE DESCRIPTION OF A RESEARCH ETHICS IS THE GOAL OF A RESEARCH PROJECT OR CLINICAL TRIAL IS GENERALIZABLE KNOWLEDGE WE'RE LOOKING TO SEE HOW WE CAN ANSWER A SCIENTIFIC QUESTION AND WE LOOK AT VARIOUS PARAMETERS, VALUE OF THE SCIENTIFIC QUESTIONS AND VALIDITY, FAIR SELECTION AND FAVORABLE RISK BEN -- BENEFIT RATIO AND THE PRIMARY QUESTION THOUGH IS GENERALIZABLE KNOWLEDGE. CONTRAST WITH THAT WITH CLINICAL ETHICS AND CARE. THE PRIMARY GOAL IN CLINICAL CARE IS TAKING CARE OF THE PATIENT AND THE SYMPTOMS IN FRONT OF YOU. AGAIN, THE GUIDING CLASSICAL PRINCIPLES ARE THINGS LIKE AUTONOMY AND JUSTICE AND MAKE SURE THE PATIENT HAS INFORMED CONSENT AND A CONNECTION BETWEEN THE PHYSICIAN NOT ONLY THROUGH THE EVENT OF THE TREATMENT AND THE FOLLOW-UP PERIOD YOU'RE THERE FOR THE PATIENT AND THEY'RE NOT ABANDONED AND THEY FEEL THEY HAVE FOLLOW-THROUGH ON IT TREATMENT YOU RECOMMENDED OR PERFORMED. AND I'M BORROWING THE EMOJIS FROM DR. MAVERICK'S TALK AROUND WENT THROUGH THE WAY OF IT CAN GO WELL AND NOT WELL. THERE COULD BE A SUCCESSFUL TRIAL AND EVERYTHING'S GREAT. YOU CAN HAVE THOSE WHERE MAYBE THE TRIAL IS NEGATIVE BUT THEY GOT BENEFIT FROM THE TILE AND IT'S A CONFUSING SITUATION. A PATIENT IN A SUCCESSFUL TRIAL THAT DOESN'T GET IT BENEFIT AND YOU HAVE TO DEAL WITH THAT. AND THE PATIENT IN A NEGATIVE TRIAL WHO ALSO HAS NO BENEFIT. AS THE THROWS PATIENTS AS WELL. WHERE IT'S THAT FIT? I THINK IT COMES TO THEORETICAL QUESTIONS HOW WE STRUCTURE CLINICAL TRIALS WA -- WHAT ETHICS AND WE TALK ABOUT THE THERAPEUTIC OPTIMISM WITH PATIENTS. EVEN MORE THAN THE CONSENT PROCESS IT STRUCTURES CLINICAL TRIALS. OUR IDEA IS MOTIVATED ON HELPING THESE PEOPLE. THERE'S THE HAPPY AND SAD FACES THAT HAPPEN AND FOLLOW-UP THAT HAPPENS AFTERWARDS. EVEN THE FACT WE'RE HAVING THE PANEL ON POST-TRIAL RESPONSIBILITIES SUGGESTS THERE'S THERAPEUTIC MISCONCEPTION IN TRIALS IN GENERAL. THERE'S CLINICAL INVOLVEMENT. IT'S THERE AND MAYBE WE DON'T ADDRESS IT IN THE STRUCTURE OF TRIALS FROM THE BEGINNING. THERE'S A HAWTHORNE EFFECT THAT HAPPENS IN THE PROCESS AND CLINICAL TRIALS. IT'S DESCRIBED FROM WATCHING FACTORY WORKERS AND YOU CHANGE LIGHTING AND SLEEPING CONDITIONS AND SEE IF THEY WERE MORE HAPPY OR PERFORMED BETTER. WERE THEY ACTING DIFFERENTLY BECAUSE WE WERE OBSERVING OR THE CHANGE THAT PRODUCED THIS. FOR PATIENTS YOU CAN HAVE A PATIENT WHO MAY BE ENROLLED FOR DEPRESSION OR OCD OR TREMORS WHO MAY IMPROVE FOR A PERIOD OF TIME AND HAVE COMPLICATION AND UNFORESEEN SIDE EFFECTS THAT CHANGE THE PERCEPTION OF THEIR RISK BENEFIT RATIO AND CHANGE THE DESIRE TO HAVE THE DEVICE EXPLANTED. IT GOES ON AFTER THE TRIAL AS WELL BECAUSE THE INITIAL IMPLANT WAS PUT IN WITH A CERTAIN EXPECTATION. THERE'S CLINICAL CONCERNS THAT ARISE. THEN THE QUESTION HELEN RAISED IS WHEN DOES THE RESEARCH DEVICE BECOME A THERAPEUTIC DEVICE. IS THERE A PROCESS WHERE IT BECOMES MORE THERAPEUTIC AND EVEN AFTER THE TRIAL'S DONE THEN IT'S A THERAPEUTIC QUESTION. DOES IT HAPPEN FROM THE SECOND THEY'RE CONSENTED OR IMPLANTED? PATIENTS WITH PARKINSON'S DISEASE ARE DIFFERENT THAN PATIENTS WHO HAVE DEPRESSION. THEY MANY MORE MEDICAL MORBIDITIES AND IT WILL BE DIFFERENT BECAUSE THEIR MEDICAL PROFILE'S DIFFERENT. OTHER QUESTIONS. THE EFFECT OF THE DEVICE, THE DURATION AND FUNCTION ETCETERA. IF A PERSON HAS IMPLANT FAIL FOR PARKINSON'S OR TREMORS AND IMMEDIATELY THEIR SYMPTOMS RECUR IS THAT DIFFERENT THAN A PERSON WHO HAD A BENEFIT WITH DEPRESSION IS NOW SUICIDAL. ARE WE DEAL WITH DEPRESSION OR PARKINSON'S. THE LENGTH OF THE IMPLANT AND MAINTENANCE AND DISCONTINUATION MATTERS. THE MEDICAL COMORBIDITIES AND WHAT HAVE YOU. THE INSURANCE OF COVERAGE AFTERWARDS. IF AN INVESTIGATOR AND HAVE YOU TO FUND CARE FOR THE PATIENT OUTSIDE THE TRIAL, HOW'S THAT DONE? WAS THAT ADDRESSED FROM THE BEGINNING WHEN YOU GOT THE GRANT OR WHEN YOU CONSENTED THE PATIENT OR WAS IT THOUGHT OF IF THE POST-TRIAL PERIOD? WHAT CAN WE DO TO FIX THAT AND ID VERSUS HD. AND EVEN THE OFF LABEL THINGS WHERE WE IMPLANT IN PATIENTS AND TRY TO MOVE AHEAD. AND THIS IS FROM THE POST MARKET SURVEILLANCE REPORT IN HOW THE FDA IS DOING AND ANALYZING APPROVAL. YOU CAN SEE STANDARD METHODS. LIKE MEDICAL DEVICE REPORTING AND MED SUN REPORT IN HOW THEY DO IN THE POST TRIAL PERIOD. POST APPROVAL STUDIES AND PROPOSED A LARGER SURVEILLANCE NETWORK. ANOTHER WAY IS DEVICE REGISTRIES. AS A PART OF DOING THIS RESEARCH WE CREATE TRIALS WHERE WE CAN FOLLOW PATIENTS TO SEE WHAT HAPPENS OVER TIME. ESPECIALLY IN INVESTIGATOR RESEARCH YOU CAN DEAL WITH ORPHAN DISEASES. SOMETIMES YOU NEED TO EXPAND IT OVER TIME. SOME OF THE CHALLENGES FOR POST TRIAL OUTCOMES ARE LISTED HERE. WE KNOW THERE'S A PUBLICATION BIAS. IF WE GET A POSITIVE RESULT WE'LL REPORT IT. IF WE GET A DIFFERENT RESULT WE'LL IMPACT WHAT WE KNOW ABOUT COMPLY -- COMPLICATIONS WE HAVE A KNOWLEDGE GAP. AND DOES IT HAPPEN INVESTOR VERSUS INDUSTRY INITIATED TRIALS WHERE YOU MAY MOVE FROM INSTITUTION TO INSTITUTION AND MAY NOT BE ABLE TO TRACK EASILY OVER TIME THE PATIENTS. THE FDA POST APPROVAL STUDIES. THERE'S BEEN ARTICLES WRITTEN WHICH ARE SMALL AND SPECIFIC TO CERTAIN QUESTIONS THAT HAVE TO DO WITH THE DEVICE AND USUALLY DON'T ADDRESS DEVICE PERFORMANCE, RARE EVENTS OR AALLOW COMPARE ALLOW COMPARISONS ACROSS DISEASES OVERTIME. AND I DO OUTCOME RESEARCH. THERE'S THE ROLE OF DATA REG STR TRY -- REGISTRY. YOU NEED TO TRACK THE OUTCOME FOR PATIENTS AND WHEN YOU CHANGE POLICIES OR PROCEDURES OR CARE PATTERNS YOU'RE SUPPOSED TO LOOK AT THE DATA AND DO A CONSTANT QUALITY IMPROVEMENT BASED ON DATA SOMETIMES SUBMITTED TO THE NATIONAL TRAUMA DATA BANK BUT IT'S ONE WAY TO LOOK AT POST-TRIAL OUTCOMES BUT THEY'RE SPARSE AND RARE AND EXIST FOR SOMETIMES TOUR TOURETTE'S TOURETTE'S DISEASE AND IT MAY DEPEND ON THE COUNTRY YOU'RE IN AND THE DEVICE AND DISEASE INDICATION AND THERE'S A LACK OF LONG-TERM PROSPECTIVE DATA. WE LOOKED AT THALAMIC PAIN SYNDROME AND HAD HE GOT FUNDING AND HE WENT THROUGH THE PROCESS OF GETTING A TRIAL STARTED. I WANT TO SHOW THIS BECAUSE I ALSO WANT TO POINT TO THE FACT OF HOW DIFFICULT IT CAN BE TO GET THE TRIAL OFF THE GROUND AND THEN FOLLOW WHAT HAPPENS. HE GOT NIH APPROVAL AND HAD TO GET INSURANCE APPROVAL FOR THE DEVICE AND MADE SURE IT CARRIED THROUGH THE DUR OF THE TRIAL AND WENT TO THE FDA AND GET THE IDE SUBMITTED AND WENT TO INDUSTRY AND ASKED FOR THE RIGHT OF REFERENCE LETTER TO USE THE DEVICE IN THE STUDY AND THEN HAD TO GO THROUGH SEVERAL ITERATIONS TO WORK ON GETTING THE DEVICE APPROVED AND THE STUDY PROTOCOL APPROVED FOR THE STUDY ITSELF. YOU CAN SEE WHAT AN ITERATIVE PROCESS IT WAS BACK AND FORTH THROUGH DIFFERENT AGENCIES TO LOOK AT THE STUDY. NOW, ADD TO THAT WE WANT TO DO DEVICE REGISTRIES AND ADD IN A DATA REGISTRY AND COLLECT FROM THE BEGINNING. THERE'S ANOTHER BAR NOW. IF YOU'RE AN INDEPENDENT REGISTER HOW DO YOU MANAGE THAT AND FOLLOW PATIENTS CLINICAL OUTCOMES. YOU CAN LOOK AT THE LIFE CYCLE AND ASKING WHAT IS THE LIFE CYCLE AND WHAT WE CAN EXPECT FOR THE DISEASE AND DEVICE IN PARTICULAR. AND WE CAN LOOK AT PATIENT MOVE FROM DIFFERENT SYSTEMS AND MEDICAL RECORDS AND PROMOTING DEVICE REGISTRIES WHETHER FOR DEVICES OR DISEASES OR BOTH AND MAKING THE PACKAGED INTO THE ACTUAL FUNDING FOR THE STUDY AND APPROVAL PROCESS AND TRYING TO BUILD THIS IN SOME WAY SO WE CAN KEEP TRACK OF WHAT HAPPENS TO PATIENTS LONG-TERM. THERE'S THE IDEA OF MEASURING HAWTHORNE EFFECTS. HOW DO PATIENT'S PERCEPTION OF THE OUTCOMES CHANGE. IN WHAT DISEASES DOES IT HIT HAPPEN IN. IS PARKINSON'S DIFFERENT THAN DEPRESSION AND OCD. WHAT DO WE DO? WHAT HAPPENS IN TERMS OF PRAGMATIC OUTCOME STUDIES. HOW OFTEN ARE DEVICES CHANGED OR EXCHANGED ACROSS DISEASE CONDITIONS. WE DON'T THE THE ANSWERS TO THE QUESTIONS. WE MENTIONED THIS BEFORE BUT A STAGED OR ITERATIVE CONSENT PROCESS FOR A REMOVABLE OR EM EXPLANTED DEVICE AND SETTING EXPECTATIONS. THEY EXPECT A CONNECTION WITH SOMEBODY WHO WILL TAKE CARE OF THEM EVEN OUTSIDE OF THE TRIAL PARAMETERS. THAT'S AN EXPECTATION. I DON'T KNOW WE'VE STRUCTURED OUR ETHICS TO ACCOMMODATE THAT OR MEASURED IT. THOSE ARE PRACTICAL STEPS WE CAN TAKE TO ANSWER THE QUESTION. I'D LIKE TO THANK EVERYBODY AND THE PEOPLE WHO HELPED ME AND I THINK I'M WITHIN TIME. >> WE'LL HAVE EXTRA TIME FOR DISCUSSION, HOPEFULLY. WE HAVE DR. KATRINA HUTCHINSON IN FROM NEW SOUTH WALES, AUSTRALIA IF THE DEPARTMENT OF PHILOSOPHY. THANK YOU FOR JOINING US TODAY. >> THANKS FOR HAVING ME AND NATURAL FOR INVITING ME. THANKS FOR HAVING ME. I'LL MAINLY BE TALKING ABOUT MAINTENANCE. THIS DRAWS OB A PAPER I CO-AUTHORED WHERE WE THOUGHT ABOUT ETHICAL ISSUES THAT ARISE IN THE MAINTENANCE OF ARTIFICIAL ORGANS. WHAT I AM TRYING TO DO IS TELL YOU THE FRAMEWORK WE DEVELOP FOR ARTIFICIAL ORGANS. WE USED PACE MAKERS AS A PROXY TO THINK ABOUT WHAT ISSUES ARTIFICIAL ORGANS MAY GIVE RISE TO AND IT'S NOT A BAD PROXY FOR THE NEUROIMPLANTS. I'LL TELL YOU WHAT THE FRAMEWORK WAS WE DEVELOPED. IT'S A FRAMEWORK FOR WORKING OUT WHAT THE ETHICAL ISSUES ARE GOING TO BE RATHER THAN A FRAMEWORK OF THE ETHICAL ISSUES. IT'S A SET OF QUESTIONS YOU ASK OR ASPECTS OF DEVICES THAT MAY OR MAY NOT BE RELEVANT TO ANY GIVEN ONE. I'LL QUICKLY TELL YOU ABOUT WHAT IT IS AND WHETHER IT'S RELEVANT TO NEURAL IMPLANTS. THE FIRST ASPECT TO THE DEVICE THAT SEEMS TO GIVE RISE TO ETHICAL ISSUES THEY'RE IMPLANTABLES. ONCE IT'S INSIDE YOUR BODY IF IT NEEDS MAINTENANCE, REPLACEMENT OR REPAIR, BATTERY CHANGE OR UPGRADE IT'S NOT ACCESSIBLE LIKE A DEVICE IS THAT'S OUTSIDE THE BODY AND REQUIRES A PROCEDURE OR SURGERY OR SOME KIND OF WIRELESS CONNECTIVITY TO UNDERTAKE THE MAINTENANCE. SURGERY HAS INHERENT HARMS AROUND RISKS ASSOCIATED WITH BLOOD LOSS AND RISK AND SO ON THAT MAY BE UNDESIRABLE. I WAS INTERESTED IN THE NONINVASIVE DEVICES AND THE NONINVASIVE NEURAL DEVICES REQUIRE ANESTHESIA AND THE OTHER THING THAT WAS RELEVANT IS THE ROLE OF THE MULTIDISCIPLINARY TEAM. CLINICIANS, TECHNICIANS WORKING TOGETHER. IF THERE IS SOFTWARE AND IF THERE IS WIRELESS CONNECTIVITY THEY SEEM TO GIVE RISE TO AN IMPORTANT SET OF ISSUES AROUND THE NEED FOR SOFTWARE UPDATES. SECURITY MEASURES AND MANAGEMENT OF DATA. IF IT DEVICE IS UNDERGOING ITERATIVE DEVELOPMENT IT CAN CONTINUE WELL AFTER THE THING IS IN AS WELL AS FOR OTHER REASONS THAT CAN GIVE RISE TO CHALLENGES WITH MAINTENANCE AND IF THERE'S COMMERCIAL PARTNERSHIPS THEY CHANGE THE DIMENSIONS OF THE PROBLEMS. WHAT I'LL DISCUSS IS HOW THEY SEEM TO APPLY TO INVASIVE NEURAL DEVICES. FIRST OF ALL, THE DEVICES I'M INTERESTED IN ARE IN THE BODY AND IT CAN INVOLVE HARMS AND RISKS INHERENT IN SURGERY NOT JUST PAIN AND INFECTION AND RISK OF MORBIDITY BUT WITH THE INCONVENIENCE OF HAVING TIME OFF WORK AND FOR RECOVERY. THEY SOMETIMES GIVE RISE TO MEDICINE OUTSIDE THE AREA WHERE YOU INITIALLY HAD THE DEVICE IMPLANTED AND IMPACTED TO EMERGENCY AND IMPLANTED DEVICE IS SOMETHING PEOPLE DON'T KNOW THERE. THEY FEED TO FIGURE THAT OUT MAYBE. ESPECIALLY CERTAIN DEVICES DON'T WORK WELL WITH OTHER SCANS AND THERE'S A SET OF ISSUES ONCE SOMETHING IS IMPLANTED WHETHER IT'S DEVISED IN BODY OR ONCE IMPLANTED IT BECOMES PART OF THE PATIENT. AND IT MAY BE SOMETHING DONE TO THEM AS OPPOSED TO HAPPENING TO THEIR DEVICE. THERE'S QUESTIONS ON WOULD OWNS IT AND WHAT SORT OF CONSIDERATIONS ARE RELEVANT WITH TREATMENT. AND NEURAL IMPLANTS MAY GIVE RISE TO SPECIFIC CHALLENGES IN TERMS OF THE IMPACT THEY HAVE ON IDENTIFY. -- IDENTITY AND POTENTIALLY AND IMPLANT AND EXPLANT QUESTIONS. AND I THINK THIS IS RELATED TO THE QUESTION OF WHO PROVIDES THE CARE AS WELL, IS WHETHER MAINTENANCE IS REGARDED AS A TYPE OF CLINICAL CARE OR TYPE OF TECH SPOUPPORT. IF YOU HAVE AN ELECTRONIC DEVICE IT REQUIRES MAYBE PROGRAMMERS AND UNDERSTANDING OF THE TECHNICAL ASPECTS OR THE SOFTWARE TO DO IT. WILL IT BE THOSE PEOPLE WHO DON'T HAVE A CLINICAL BACKGROUND PATIENT DOING THE PROGRAMMING OR WILL IT BE CLINICIANS OR PEOPLE WITH MEDICAL BACKGROUND. THAT WILL BE ASSOCIATED WHETHER THEY'RE FAMILIAR WITH THE PRINCIPLES OF MEDICAL ETHICS AND IT MAKES A DIFFERENCE WHETHER THE PATIENT IS UNDER ANESTHESIA OR NOT. AND I TALKED TO PEOPLE INVOLVED IN AN INNOVATIVE EPILEPSY FACILITY IN SYDNEY. IF IT'S DEPRESSION MAYBE THERE'S A PSYCHIATRIST INVOLVED AS WELL. I THINK THERE'S A QUESTION FIRST AND I DON'T HAVE A BULLET ON THIS ON WHETHER THE PEOPLE SEE THEMSELVES AS BEING PART OF A MULTI DISCIPLINARY TEAM AND NOT TALKING TO ONE ANOTHER AND MAKING SHARED DECISIONS AND I THINK THAT'S AN IMPORTANT QUESTION AND IT'S IMPORTANT IN BEING A MULTICOLLABORATOR. IT MAY BE INDUSTRY THE COMPANY THAT MANUFACTURERS THE DEVICE THAT THEY'RE PLEMPLOYEES ARE THE TECHNICIANS. HOSPITALS MAY HAVE THEIR OWN TECHNICIANS. THIS MAY VARY FROM CASE TO CASE. THE DISEASES DIFFER AND WHO IS PART OF THE TEAM WILL DIFFER DEFENDING ON WHAT CONDITIONS ARE BEING TREATED. I'VE TALKED THROUGH WHO THE PEOPLE ARE BE AND ALLIED HEALTH. PEOPLE IN SYDNEY GOT THE ALLIED HEALTH AND THE SPECIALIST NURSE AND TECHNICIANS AND NEUROSURGEON AND SPECIALIST PHYSICIAN AND NEUROLOGISTS AND THEY WERE CLASS RATING BUT I DON'T THINK THAT ALWAYS HAPPEN S. IT'S ONE THING WHEN IT'S BEING PUT IN THE PATIENT BUT SEPARATE WHEN THE PATIENT COMES BACK FOR FOLLOW-UP CARE AND THEY WORK TOGETHER AND COMMUNICATE WITH ONE ANOTHER TO ENSURE FOLLOW-UP IS DONE IN A SENSIBLE AND EFFICIENT WAY. AND PACE MAKERS ARE PROGRAMMED EXTERNALLY WITH WIRELESS TECHNOLOGY. IT MITIGATES THE PROBLEMS ASSOCIATED WITH SURGICAL MAINTENANCE. IT RAISES A DIFFERENT SET OF PRACTICAL AND ETHICAL CONCERNS AROUND DEVICE SECURITY AND OFTEN YOU WANT THE DEVICES TO BE ACCESSIBLE TO SPECIALISTS HEALTH PRACTITIONERS MAYBE IF A PATIENT'S IN A DIFFERENT PLACE WHO IS NOT PART OF THE ORIGINAL TEAM SO ACCESSIBILITY PARTICULARLY EMERGENCY MEDICINE CAN BE IMPORTANT BUT AT THE SAME TIME YOU DON'T WANT THEM WIRELESSLY ACCESSIBLE TO JUST ANYBODY. PARTICULARLY PEOPLE WHO HAVE MALICIOUS INTENT. THERE'S THE TRADE-OFF BETWEEN ACCESS FOR THE PATIENT'S OWN SAFETY AND ACCESSIBILITY THAT MAY PUT THE PATIENT AT RISK. THEN THERE'S THE QUESTION AROUND ACCESSIBILITY OF THE DEVICE PATIENT. I KNOW SOME HAVE A PATIENT CONTROLLER WHICH ENABLE PATIENTS TO HAVE LIMITED CONTROL OVER THE SETTINGS. OTHERS DON'T. SOME THINK THEY IS SHOULD HAVE ACCESS IN WHAT'S BEING RECORDING ABOUT THEM AND WHO OWNS IT AND WHAT RELATIONSHIP THE DEVICE HAS TO THE PATIENT'S OWN BODY. THERE'S PATIENT RISKS AND BENEFITS SO IF PATIENTS HAVE ACCESS TO CONTROL BUT DON'T KNOW WHAT THEY'RE DOING THERE COULD BE RISK ASSOCIATED WITH THAT. TIMELY THERE'S A SET OF QUESTIONS ON WHETHER THE DEVICE RECORDS INFORMATION AND THERE CAN BE DIFFERENT MODELS AND THE CAN CHANGE AS TIME GOES ON. INNOVATIVE DEVICES CAN BE SUBJECT TO ITERATIVE CHANGE. YOU HAVE A PROTOTYPE, YOU SEE HOW IT WORKS. YOU MAYBE MAKE TWEAKS AND HAVE A NEW PROTOTYPE. THIS POSES CHALLENGES FOR SUPPORT FOR OBSOLETE MODELS. TO BE ABLE TO MAINTAIN ONE DEVICE AND WHO HAS WHAT AND WHAT SPARE PARTS ARE NEED OR WHAT BATTERIES ARE REQUIRED FOR TWEAKS OVER TIME. THERE ARE OBLIGATIONS THAT REMAIN FOR LESS EFFECTIVE MODELS AND THERE COULD BE OPPORTUNITY COSTS IF EXPLANTATION CAUSES HARM OR IF THEIR NEW DEVICE ISN'T AS GOOD AS LATER MODELS. THERE'S QUESTION ON PATIENT FAMILIARITY. THIS COULD BE COMPOUNDED BECAUSE THE RISKS COULD BE UNKNOWN AND YOU MAY HAVE THE PROBLEMS THAT WOULD LEAD TO REFINEMENT OF THE EARLY PROTOTYPES AND HAVING TO TELL PATIENTS ABOUT UNEXPECTED PROBLEMS THAT HAVE ARISEN AND HAVE HARD CONVERSATION. LASTLY THERE'S A QUESTION ABOUT WHAT HAPPENS DOWN THE TRACK AND THOSE PEOPLE CAN'T PROVIDE THE FOLLOW-UP ANY MORE BECAUSE IT CONTRIBUTES AND WHEN IT'S AN ESTABLISHED DEVICE COMPANY THEY MAY HAVE A MUCH BETTER MODEL FOR WIDE SPREAD FOLLOW-UP CARE AND MAY GIVE RISE TO CONFLICT QUESTIONS AND THERE'S A PRACTICAL QUESTION ON PROVIDING MAINTENANCE AND THAT MAY BE SOMEBODY EMPLOYED BY THE DEVICE COMPANY AND AN ETHICAL ISSUE ON WHAT IS BET FOR THE PATIENT AND THE HEALTH SYSTEM. FINALLY, THERE ARE A SET OF CONCERNS ABOUT THE COMMERCIAL CONSIDERATIONS EFFECT WHO PROVID PROVIDES MAINTENANCE. THE TIMELINESS. SOMEONE FROM A PARTICULAR COMPANY MAY HAVE TO TRAVEL AND HOW THE COST IS DISTRIBUTES OVER THE LIFE TIME OF THE DEVICE AND KNOWLEDGE-SHARING PRACTICES. SO IF A REP IS IN THE HOSPITAL THEY MAY HAVE A DISINCENTIVE TO SHARE THAT SUPPORT. THERE ARE QUESTIONS ON BUILT-IN OBSOLESCENCE AND THE POTENTIAL LIMITS FOR A PARTICULAR MODEL. THESE ARE MUCH WORSE IF THE DEVICE IS IMPLANTED. IT EFFECTS WHO CONTROLS THE SOFTWARE AND THE IMPROVEMENTS IN THE LIFE CYCLE. I'M INTERESTED WHETHER THIS IS A USEFUL FRAMEWORK FOR NEURAL IMPLANTS. I JUST HAVE A RECAP AND THERE'S PARALLELS BETWEEN DBS AND PACE MAKERS AND I'M INTERESTED WHETHER THIS IS PRACTICAL TO USE AND IF DIFFERENT STAKEHOLDERS HELP IDENTIFY WHAT THE ISSUES WERE. I WANT TO ACKNOWLEDGE ROB WHO I CO-AUTHORED THE PEOPLE AND THE PEOPLE AT THE UNIVERSITY I WORK WI WITH. [APPLAUSE] >> OUR LAST PANELIST IS FROM THE UNIVERSITY OF WASHINGTON, SEATTLE. >> THANKS. >> OKAY. LAST ONE. WE'RE ALMOST THERE. THANK YOU FOR STAYING WITH ME AND FOR INVITING ME. IT'S BEEN AN INTERESTING DAY SO FAR. I WANT TO STAY A LITTLE BIT ABOUT MY POSITIONING. OUR CENTER IS WORKING ON PRINCIPLES FOR BIDIRECTIONAL BRAIN COMPUTER INTERFACES AND MOSTLY FOCUSSED ON MOTOR BCI BUT WE HAVE TALKED TO GROUPS AT MGH ABOUT DEPRESSION. SO WE'RE THINKING ABOUT ELECTRICAL ENGINEERS AND OTHERS, AND SO I FEEL WE HAVE GOTTEN GOOD UP TAKE FOR THE IMPORTANCE OF THE IDEAS ABOUT ETHICS THERE, ONE PART OF WHAT WE DO IS NORMATIVE WORK LOOKING AT QUESTIONS ABOUT -- ABOUT PRIVACY, AGENCY, IDENTITY, RESPONSIBILITY, JUSTICE AND MAYBE NORMALITY, KAREN SAID SOMETHING ABOUT NEURO DIVERSITY. WE WANT TO THINK ABOUT WHAT WE ARE TRYING TO GET PEOPLE TO DO WITHIN A FRAME OF INCLUSION, RECOGNIZING THERE ARE MULTIPLE MODES OF DOING THINGS SUCCESSFULLY. ANOTHER GROUP IS MAKING SURE, IN PART BECAUSE WE ARE SENSITIVE TO THESE DIFFERENT APPROACHES AND VALUES IN THE WORLD RELATED TO DISABILITY AND DIFFERENT MODES OF FUNCTIONING, WE WANT END-USER ENGAGEMENT, THAT'S AN ENGINEERING WORD. I DON'T ALWAYS WANT TO SAY PATIENT. THEY AREN'T ALWAYS PATIENTS. WE HAVE DONE FOCUS GROUPS AND INTERVIEWS WITH ACTUAL USERS AND POTENTIAL USERS, PEOPLE WITH S.E.I. OR STROKE. ONE THING I WANT TO TALK ABOUT IN MY PART OF THE RESPONSIBILITY SECTION, WHAT SOME OF THE PEOPLE WE TALK TO SAY ABOUT RESPONSIBILITY. SO GOING TO THEM. THIS IS JUST ABOUT THINKING WHAT THEIR EXPECTATIONS ARE, AND MORAL FRAME AROUND OBLIGATIONS ARE. FOR INSTANCE THIS GROUP ERIN TALKED ABOUT AND HAD GREAT QUOTES OF OTHER TOPICS, ON THIS ISSUE OF WHETHER OR NOT RESEARCHERS HAVE OBLIGATIONS TO CARE FOR THEM POST-TRIAL, HERE IS A SMATTERING OF THINGS WE HAVE HEARD, I EXPECT SOMEONE WILL CONTINUE TO TAKE CARE OF THEM, IF THE DEVICE NEEDS PERKING OR RUNS OUT OF BATTERY OR WHATEVER, WHOEVER WAS MANAGING WILL CONTINUE TO MONITOR THE DEVICE. THEY WILL BE ABLE TO GO BACK AND HAVE WHATEVER TWEAKS OR BATTERIES, RIGHT. THIS IS AN ONGOING OBLIGATION. PEOPLE IN THE STUDY SHOULD EXPECT THE LEVEL OF CARE AND ATTENTION WILL CONTINUE AFTER THE TRIAL SOEFR. THEY AREN'T CUT LOOSE ON THEIR OWN. I DID SOMETHING FOR YOU, I VOLUNTEER TODAY BE PART OF T BUT I INVESTED AND I EXPECT YOU TO BE INVESTED IN A RECIPROCAL WAY. SOMEONE SAYS I THINK THE REASONABLE EXPECTATION IS TO COMPLETELY AND FULLY EXPECT PEOPLE WHO STARTED THIS DEAL STAY WITH YOU FOR THE REST OF YOUR LIFE. THAT IS A BIG STATEMENT. THE REST OF YOUR LIFE. SO WHY THE REST OF YOUR LIFE? YOU WANT TODAY LEARN FROM US, THIS IS CALLING A DIFFERENCE BETWEEN PHARMACEUTICALS AND IMPLANTABLE DEVICES. THIS WILL BE IN ME UNLESS THERE'S AN REASON TO GET IT EX-PLANTED, I WILL NEED SOMEBODY TO BE WITH ME AND PART OF ME. ASSUMING EVERYTHING IS RIGHT SHOULD LAST BETWEEN 7-8 YEARS. THEY ARE PART OF A STUDY THEY ARE GIVEN A NEW BATTERY BUT THEN WHAT? WHAT HAPPENS AFTER THAT, IF IT'S NOT COVERED BY INSURANCE, WHO WILL CHANGE THE BATTERIES. A REAL CONCERN ABOUT WHAT HAPPENS FROM HERE ON OUT. NOW STEPPING AWAY FROM THE END USER GROUP, OUR GROUP ALSO WENT TO THE INTERNATIONAL B.C.I. MEETING AND DID A SURVEY, ACTUALLY NOT THERE, IT WAS A WEB SURVEY ABOUT PRINCIPLES OR GUIDELINES FOR GUIDING B.C.I. RESEARCH. I WANT TO POINT OUT THE RESEARCHERS WE WERE TALKING TO, DOING BOTH IMPLANTABLE AND NON IMPLANTABLE B.C.I. THEY AGREED THEY SHOULD BE BOUND BY, ASPIRING, I'M NOT SURE WHAT THE LANGUAGE SHOULD BE, WAS CARE OF SUBJECTS, WHICH MEANT, AS ONE POSSIBILITY AT THE BOTTOM, ENSURING SUBJECTS HAVE APPROPRIATE CARE EVEN AFTER COMPLETION OF THE STUDY. THAT DOESN'T SAY PROVIDING IT. ENSURING THAT IT'S THERE, BUT THE RESEARCHERS THEMSELVES ARE RECOGNIZING THIS KIND OF OBLIGATION. IT'S PART OF WHAT I OWE WHEN I HAVE THIS DEVICE TO MAKE SURE SOMEBODY GETS APPROPRIATE CARE. JUST A COUPLE EXAMPLES TO GET US THINKING ABOUT THIS, THE NEURO CONTROL, THE FREEHAND SYSTEM IS A GOOD EXAMPLE FROM CASE WESTERN WHERE HUNTER PECKHAM WORKED TO GET THIS CONTROL SYSTEM FOR MOTOR MOVEMENT APPROVED, IT WAS WORKING AND THEN THE COMPANY FOLDED. WELL WHEN THE COMPANY FOLDS THERE ARE ALL THESE PEOPLE WHO HAVE IMPLANTED WIRES WHO HAVE BEEN HELPING THEM, THEY HAVE BEEN SUCCESSFULLY USING THE DEVICE. WHAT HAPPENS TO THEM? BECAUSE THE WIRES BREAK, SOMETHING GOES WRONG WITH THE SYSTEM, RIGHT. THEY NEED THE KIND OF UPKEEP AND MAINTENANCE KATRINA WAS TALKING ABOUT. AND PECKHAM AND HIS GROUP CAME UP WITH A PLAN TO HAVE SOME SORT OF INSTITUTIONAL SUPPORT TO MAKE SURE THEY ARE CLOSE TO 250 USERS WOULD HAVE THIS SORT OF FOLLOW-UP CARE. THROUGH THE COURSE OF THEIR LIVES AS THEY HAVE THESE THINGS. BUT AS BAUCHER AND OTHERS SAID IN THIS PIECE IN 2016, IT'S NEVERTHELESS CLEAR DEVELOPERS COMMERCIAL VIABILITY HAS LASTING EFFECTS ON THE USER EXPERIENCE. WE HAVE TO THINK ABOUT WHAT WILL HAPPEN WHEN IT TURNS OUT NOT TO BE A MARKETABLE THING VIABLE FOR INDUSTRY OR AS HELEN WAS SAYING IF THE TRIAL FAILS AND SOMEBODY PULLS OUT, WHAT HAPPENS THEN? I ALSO WAS TALKING THINKING OF THE TRIALS AS THEIR TYPICAL PROTOCOL AND EXPLANT. A DEVICE IS IMPLANTED BUT AT THE END OF THE STUDY, IT MIGHT BE FIVE YEARS, IT MIGHT BE LONGER THAN THAT, THE IDEA IS NOW THE DEVICE, THE IMPLANTED DEVICE IS NO LONGER PROVIDING ANYTHING. IF IT DOES ANYTHING IT IS PROVIDING THE OPPORTUNITY FOR RISK OF INFECTION OR FAILURE. THE NORM WOULD BE TO EXPLANT IT. I REMEMBER GOING TO A MEETING AND HEARING SOMEONE FROM ONE OF THESE STUDIES, I DON'T KNOW WHO IT WAS SO I CAN'T NAME NAMES. WE WANTED TO EXPLANT THIS WOMAN, SHE DIDN'T WANT IT EXPLANTED SO WE WERE IN A CONUNDRUM. WE CAN'T FORCE HER TO UNDERGO A SURGERY TO HAVE THIS OUT. IN THE END THEY WERE RELIEVED BECAUSE THERE WAS SOME INFECTION AND THEY HAD A MEDICAL REASON. BUT THIS ISN'T THE SITUATION WE WANT TO END UP IN, WE WANT TO FIGURE OUT, WHAT IS THE LONGER TERM CARE FOR SUCH THINGS. AND TALKING ABOUT THE BRAIN GATE STUDY, WAS SAYING WITH BRAIN GATE THEY ARE WIRED RIGHT NOW. SO THEY DO IT AT HOME. SOMEONE GOES THERE, SOMEONE HAS TO BE VERY NEAR TO THE PERSON USING THE DEVICE IT MAKE IT WORK. SO A TECHNICIAN WHO IS KNOWLEDGEABLE NOT ONLY ABOUT THE DEVICE BUT MAT LAB AND OTHER THINGS. THE NEXT PHASE WILL BE WIRELESS AND PRESUMABLY WHERE SOMEONE COULD KEEP THE DEVICE IN AND USE IT AT HOME. WHEN THEIR STUDY ENDS, HE SAID I WILL TELL YOU, WE FEEL LIKE WE ARE RESPONSIBLE. WE WANT TO BE RESPONSIBLE. BUT WE ALSO FEEL VERY CONSTRAINED BY THE ENVIRONMENT OF THE GRANTS. BECAUSE OUR STUDY ENDS AND OUR MONEY ENDS AND IF WE HAVEN'T USED IT, IT GOES BACK, RIGHT. SO HE TALKED IN THE LANGUAGE OF DO WE NEED SOMETHING LIKE AN EXPLANT ESCROW, SOME SORT OF THING THAT WOULD HAVE A LONG-TERM RANGE THAT WOULD ALLOW RESEARCHERS WHO DO RECOGNIZE THIS OBLIGATION TO GO BACK AND HAVE THE FUNDING. I TAKE IT NOT ONLY FOR EXPLANTING BUT ALSO UPKEEP OF THE DEVICE. AND HELEN GIVES US ANOTHER GREAT MODEL OF TAKING LONG TERM CARE. NOW I WANT TO BRING WHAT I KNOW PEOPLE HERE AT N.I.H. CLINICAL BIOETHICS KNOW ABOUT, BUT I DON'T KNOW IF EVERYONE DOES. HENRY RICHARDSON'S WORK. ANCILLARY DUTIES OF CARE. I THINK WE COULD HAVE AN INTERESTING CONVERSATION ABOUT WHETHER THE LONG-TERM RESPONSIBILITIES FOR IMPLANTABLE DEVICES FALL UNDER THE CATEGORY OF ANCILLARY CARE. SO FOR RICHARDSON I THINK HE WOULD SAY IT'S TYPICALLY SOMETHING THAT ISN'T REQUIRED TO MAKE A STUDY SCIENTIFICALLY VALID TO ENSURE A STUDY'S SAFETY OR ADDRESS OR REDRESS INJURIES. THEY AREN'T INJURIES, PER SE. THEY AREN'T ABOUT SAFETY OF THE STUDY. BUT THEY ARE, MAYBE, LONGER TERM ABOUT THE SAFETY OF THE INDIVIDUAL WHO EXITS THE STUDY, WHEN THE STUDY ENDS. I THINK THE MACHINERY HE USES TO TALK ABOUT ANCILLARY CARE DUTIES COULD BE HELPFUL HERE. SO PART OF WHAT HE WANTS TO ARGUE IS RESEARCHERS AND OTHERS, HE TALKS ABOUT IT OUTSIDE OF THE RESEARCH CONTEXT, COULD ENTER INTO WHAT HE TERMS MORAL ENTANGLEMENT. WE GET TO KNOW CERTAIN THINGS ABOUT ANOTHER PERSON, BASED ON WHAT HE CALLS A PARTIAL ENTRUSTMENT MODEL. THEY GIVE YOU ACCESS TO THEIR BODY OR DETAILS ABOUT THEIR MEDICAL RECORD AND THEY ARE TRUSTING YOU TO DO GOOD WITH THAT INFORMATION AND BECAUSE OF THAT TRUST IN YOU, YOU BECOME MORALLY ENTANGLED WITH THEM. AND HE SAYS THERE ARE SPECIAL DUTIES OF BENEFOSENSE. I WANT TO FRAME THE ISSUES IN TERMS OF THESE MORAL ENTANGLEMENTS. HE SAYS WE CAN'T JUST HAVE LIMITLESS, ROBUST ENTANGLEMENTS. WE CAN THINK OF SCOPE AND STRENGTH TO TRY TO FIGURE OUT WHAT IS THE EXTENT OF THESE ANCILLARY CARE DUTIES. IS THE NEEDED CARE AND QUESTION APPROPRIATELY RELATED TO THE STUDY PROCEDURE. DOES THE DISCOVERY OF THIS NEED OR SPECIAL NEED ARISE FROM THE ACTIVITIES OF THE STUDY. AND THEN STRENGTH HE HAS A LIST OF THINGS, HOW STRONG IS THE CLAIM ON THE RESEARCHER IN TERMS OF THE VULNERABILITY OF THE SUBJECT OF RESEARCH TO THE RESEARCHER. IN TERMS OF -- OR HOW MUCH, SORRY, THE VULNERABILITY FOR THAT PERSON, RIGHT. HOW MUCH DIFFERENCE WOULD GETTING THAT CARE MAKE TO A PERSON'S HEALTH OR WELFARE. IN TERMS OF THE LEVEL OF ENGAGEMENT. IF IT'S PASSING AND I GET DATA OUT OF A DATA BANK THERE'S LIKELY LESS OF THAT ENGAGEMENT. GRATITUDE. DO RESEARCHERS OWE PARTICIPANTS A DEBT OF GRATITUDE FOR HAVING UNDERGONE STUDY PROCEDURES THAT MAY BE RISKY, PAINFUL OR INCONVENIENT. AND THE COST. HE INCLUDES THAT BECAUSE HE RECOGNIZES WE HAVE THIS REAL PRAGMATIC RESTRAINT. IT CAN'T BE LIMITLESS. SO APPLYING BACK TO IMPLANTED NEURAL TECHNOLOGY. IN TERMS OF SCOPE, IT SEEMS VERY CLEAR, RIGHT. WHEN YOU COME TO MY STUDY AND I IMPLANT SOMETHING IN YOU AND IT WILL GO WITH YOU, THAT'S WHAT I WAS INTENDING TO DO IN THE STUDY AND I CAN RECOGNIZE IN ADVANCE THIS IS A THING THAT WILL DETERIORATE OVERTIME AND NEED UPKEEP AND MAINTENANCE. IN TERMS OF STRENGTH, WHEN WE GO THROUGH EACH OF HIS FACTORS, I WANT TO SAY ABOUT IMPLANTABLE NEURAL DEVICES, THESE ARE INCREDIBLY STRONG. THE VULNERABILITY. FOR SOMEONE USING, SECOND GENERATION B.C.I. DEVICES FROM BRAIN GATE, IF THEY CAN USE IT AT HOME TO MOVE THAT ARM TO DO THINGS FOR THEMSELVES, THAT'S A HUGE GAIN IN AGENCY FOR THAT PERSON. AND THAT LOSS COULD MAKE THEM VERY VULNERABLE. THEY ARE DEPENDENT ON THAT DEVICE MAKER OR THE RESEARCHER TO HAVE ACCESS TO THAT. IT'S NOT LIKE IT'S AVAILABLE ON THE MARKET IN OTHER WAYS. THEY TYPICALLY HAVE BEEN ENGAGED IN REGULAR PATTERNS OF INTERACTION WITH THE RESEARCHERS OVER TIME. SO IT'S NOT A ONE-OFF STUDY, YOU GET TO KNOW PEOPLE IN THIS PROCESS. THE WORK WOULDN'T BE ABLE TO TAKE PLACE WITHOUT SOMEBODY WILLING TO TAKE THESE RISKS. SO WHEN SOME OF THE FOCUS GROUPS WE HAVE DONE WITH PROSPECTIVE USERS, SO PEOPLE WITH SPINAL CORD INJURY, WHAT WE HEAR REGULARLY IS I DON'T WANT TO BE PATIENT 1 OR 50 BUT AFTER OTHER PEOPLE HAVE TAKEN THE RISK AND YOU WORK OUT THE KINKS AND GO THROUGH THE FIRST BETA VERSION I WOULD BE WILLING. THERE IS AN EVEN GREATER DEBT OF GRATITUDE AND OF COURSE THE COSTS COULD BE SIGNIFICANT. I WON'T HAVE MUCH TIME FOR THIS, BECAUSE KAREN IS GOING TO HAVE THE DUCKS QUACKING IN A SECOND. IN THIS THE GROUP SET OFF ABOUT DEVICES THEY PRESENT UNIQUE CIRCUMSTANCES BECAUSE MANY ARE IMPLANTED AND THAT GETS AT THE STRENGTH ISSUES I WAS JUST TALKING ABOUT. AND ALSO PICKING UP ON WHAT KATRINA SAID BEFORE. THE COMPLEXITY, HAVING CERTAIN DEVICES GO OBSOLETE, NEEDING CLINICIANS, ALL OF IT COMPLICATES THE SCENARIO. AND MAYBE ALL I NEED TO DO ON THIS SLIDE IS SAY LOOK AT THE LAST THING. I WAS JUST READING REBECCA DRESSLER'S BOOK "SILENT PARTNERS" THINK IT'S CALLED. HOW DO WE GO ABOUT REFRAMING THE ROLE OF RESEARCHERS WE MOVED FROM SUBJECTS TO PARTICIPANTS THAT SUGGEST A LL MORE ACTIVITY. BUT SHE WANTS TO SAY "PARTNERS" AND REALLY TRY TO MAKE THAT A REALITY, RIGHT. SO WE UNDERSTAND THERE ARE KINDS OF KNOWLEDGE, KINDS OF DATA, INPUT THAT WE COULD GET FROM THE PARTICIPANTS IN RESEARCH THAT ARE GOING TO IMPROVE OUR STUDIES, NOT ONLY IN TERMS OF THE HISTOMOLOGY BUT ETHICS. WHEN WE THINK OF THE LEVEL OF ENGAGEMENT AND TYPES OF INTERACTIONS PEOPLE HAVE IN THESE STUDIES WE NEED TO THINK OF THEM IN THESE WAYS. IF WE DON'T WE RISK TREATING PATIENTS AS RESEARCH MATERIAL RATHER THAN MORAL AGENTS. THEY ARE PEOPLE WHO GO ON WITH THEIR LIVES AFTER THE STUDY. WE HAVE THIS OBLIGATION TO FOLLOWTHROUGH WITH THEM BEYOND THE EXTENT OF THE STUDY. I JUST WANTED TO BRING RICHARDSON TO THIS AND SHOW YOU WHAT SOME OF THE END USERS HAVE SAID. AND THANKS TO MY GROUP THERE. THANK YOU. [APPLAUSE] >> COULD OUR LAST GROUP COME UP TO THE TABLE. >> THANK YOU. THAT WAS REALLY INTERESTING. I WONDER IF ANY OF YOU COULD TALK ABOUT NOT JUST THE ACTUAL RESEARCH PARTICIPANTS BUT MAYBE OTHER PEOPLE WHO WERE INVOLVED. FOR EXAMPLE, THEIR CARE GIVERS WHO MIGHT HAVE A REAL STAKE IN WHAT HAPPENS TO THOSE PATIENTS IF THEY ARE EXPLANTED OR IF THE TRIAL ENDS AND THEY NO LONGER HAVE ACCESS? >> I DON'T KNOW, MAYBE HELEN CAN SAY MORE ABOUT FAMILY OR RELATIONS FROM HER GROUP. IT DOES SEEM TO ME WHEN WE TALK ABOUT THE B.C.I. STUDIES, ESPECIALLY IF THEY ARE TAKING PLACE AT HOME, SO TALKING TO LEE ABOUT THE NEXT GENERATION, BRAIN GATE, THERE ARE GOING TO BE WAYS YOU GAIN SOME LEVEL OF AGENCY AND IF YOU DON'T HAVE THAT, YOU WILL BE RELIANT ON A PERSONAL CARE ATTENDANT OR FAMILY MEMBER TO DO THAT. YOU ARE RIGHT, THEIR INTERESTS AR BOUND UP IN THIS AS WELL AS THE INDIVIDUALS. >> THE BIG ISSUE BECOMES COST. FAMILIES, WHEN WE REQUIRE PATIENTS WHO AREN'T FROM ATLANTA TO MOVE THERE, DO THEY COME ALONE? DO THEY RENT AN APARTMENT WITH A FAMILY MEMBER? DO THEY HAVE SOMEONE TO KIND OF HELP THEM? AND THEN EVEN THE COST, ONE OF THE THINGS I DIDN'T SAY, IS WE TRANSITION FROM HAVING THE GRANT PAY FOR THE SURGERIES AND DEVICE DONATIONS TO ACTUALLY HAVING TO CHANGE OUR CONSENT WHEN WE REALIZE THAT THE BATTERIES WEREN'T GOING TO LAST AS LONG AS WE THOUGHT AND THE TRIAL WASN'T GOING TO CONVERT TO F.D.A. APPROVAL TO ACTUALLY HAVE PATIENTS KNOW UP FRONT THEY WOULD BE PAYING ALL SURGICAL COSTS GOING FORWARD AND WE WOULD WORK WITH THEM TO GET THE REIMBURSEMENT, SO THERE'S A FINANCIAL, AS WELL AS A MORAL SUPPORT AND SHEPHERDING OF THEIR INVOLVEMENT. I THINK IN RETROSPECT, I THINK WE NEED TO HAVE WAYS IN WHICH TO QUERY THE FAMILIES. IT'S ANOTHER ISSUE SO THE FAMILIES ARE PART OF THE RESEARCH, AS OPPOSED TO FACILITATORS. WE HAVE FAMILY MEMBERS WHO ARE ACTUALLY THE ONES WHO CALLED US. THOSE ARE ACTUALLY THE BEST PATIENTS WHEN THE FAMILY MEMBER SEEKS OUT THE RESEARCH. ALMOST AN INVERSE CORRELATION WITH HOW WELL PEOPLE DO, IF A FAMILY MEMBER SEEKS OUT TO GET THE TREATMENT, AS OPPOSED TO THE PATIENT WRITING, BECAUSE THEY ARE USUALLY TOO IMPAIRED. SO THERE IS THIS WHOLE CONTINUUM I DON'T THINK WE HAVE DEALT WITH. YOU NEED INFORMED CONSENT FROM A PATIENT. BUT YOU EQUALLY HAVE TO WORK JUST FROM THE CLINICAL SIDE OF WHO IS GOING TO TAKE THE RESPONSIBILITY TO GO TO BATTLE WITH THE INSURANCE COMPANY. AND DEAL WITH THE BILLING DEPARTMENT AND KIND OF MAKE SURE THERE IS SOMEONE TO PICK SOMEONE UP. THEY ARE REALLY, SCIENTIFICALLY VERY KIND OF ROUTINE KINDS OF THINGS. BUT I THINK WE HAVE TO DO BETTER THAT THE FAMILY IS INVOLVED BUT CAN'T UNDERMINE A PATIENT'S AGENCY TO MAKE A DECISION ABOUT WHAT THEY DO AND WHEN. >> I THINK IT'S ALSO IMPORTANT WHEN YOU ARE LOOKING AT OUT COMES, THIS IS SOMETHING THE TRAUMATIC BRAIN MODEL SYSTEMS HAVE DONE WELL, OUTCOME BASED REGISTRY, LOOKING AT NOT JUST THE MEDICAL OUT COMES BUT THE SOCIAL FAMILY OUTCOMES AND THEY WILL MONITOR EMPLOYMENT, RETURN TO WORK, HOUSING, LIVING SITUATION, DIVORCE RATES AND ALL THESE THINGS IN THEIR REGISTRY ALONG WITH FUNCTIONAL OUTCOME MEASURES. WHAT IS YOUR ABILITY TO WALK, OR FUNCTION, YOUR DEPRESSION LEVELS, EVERYTHING ELSE. KIND OF BRINGING THE STANDARD METRICS IN TRIALS INTO MORE OF A SOCIAL DEMOGRAPHIC AREA AND BRINGING IT TOGETHER. IF YOU DON'T LOOK AT THOSE THINGS THOUGH, YOU DON'T KNOW. THAT'S WHY IF YOU ARE STRUCTURING IT YOU HAVE TO INCLUDE. >> I HAVE TO SAY SOMETHING ABOUT THE DANGER ABOUT THE BIOLOGY, IF YOU GET RID OF [INAUDIBLE] WITH PARKINSON'S AND DROP THEIR MEDICATION AND THEY HAVE A PERSISTENT COGNITIVE DECLINE BECAUSE OF THE NATURAL HISTORY OF THEIR ILLNESS AND QUALITY OF LIFE. IS THERE QUALITY OF LIFE FOR WHAT YOU INTEND TODAY DO FOR THEM YOU DID WHAT YOU NEEDED BUT IN THE BIG PICTURE THEY MAY NOT BE AS WELL AS THEY HOPED TO BE BECAUSE YOU DIDN'T TARGET THE THING THEY HAVE A PROBLEM WITH. YOUR POINT, WE TRY TO FIND BETTER MEASURES OF THESE KINDS OF QUALITY OF LIFE. IT'S VERY INTERESTING TO WATCH SPOUSES, A COUPLE HAVE A REAWAKENING OF THEIR RELATIONSHIP TO EACH OTHER. USUALLY GOOD. BUT AS OPPOSED TO BAD. BUT IT GOES BOTH WAYS. YOU HAVE PATIENTS WHO WERE TAKING CARE OF SOMEONE AND THEN ACTUALLY THEY ARE WORRIED THE PERSON WON'T LIKE THEM ANY MORE BECAUSE THE CARE GIVING RELATIONSHIP IS THERE. GETTING THE RIGHT METRIC. IF YOU HAVE BEEN DISABLED FOR 15 YEARS, TRY GETTING A JOB. SO AGAIN, NOT HAVING A BAR THAT CAN'T BE MET, BUT ACTUALLY YOU NO LONGER HAVE THE PROBLEM YOU STARTED WITH. >> I THINK COST IS SOMETHING WE NEED TO TALK ABOUT A LITTLE BIT MORE. SEEMS TO ME THE MORE I HEAR ABOUT THIS, THERE IS A GENERAL AGREEMENT WE CAN'T JUST THROW PEOPLE OUT THE WINDOW ONCE WE HAVE IMPLANTED THEM OR DONE SOMETHING THEY NEED CARE FOR. BUT THE ISSUE BECOMES, WHO PAYS FOR IT? WHO IS RESPONSIBLE FOR IT? AND I KNOW IN THE POST-TRIAL ACCESS DEBATES ABOUT DRUGS, ONE OF THE THINGS PEOPLE WORRIED ABOUT WAS THAT IF WE SAY TO RESEARCHERS OR PHARMACEUTICAL COMPANIES IT'S YOUR RESPONSIBILITY TO MAKE SURE THIS PERSON GETS THIS DRUG FOR THE REST OF THEIR LIFE, IT'S GOING TO BE A DISINCENTIVE TO STUDY CERTAIN DISEASES, CERTAIN KINDS OF DRUGS OR A DSINCENTIVE TO STUDY THINGS IN CERTAIN PLACES WHERE COSTS ARE HANDLED DIFFERENTLY. THIS IS KEY TO ME. BUT THE QUESTION I HAVE FOR ANYBODY WHO WANTS TO THINK ABOUT IT, IT WAS INSPIRED FROM WHAT MIKE SAID, DO WE NEED DIFFERENT MODELS FOR HOW WE DO RESEARCH? MAYBE IN THIS KIND OF A PLACE, YOU KNOW, WE SEPARATE, YOU GET RESEARCH FUNDING AND CLINICAL CARE FUNDING FROM ANOTHER PLACE. MAYBE WE SHOULD THINK ABOUT THAT MODEL AND MAYBE THE MODEL OF DOING RESEARCH IN CERTAIN AREAS LIKE NEURAL DEVICES SHOULD BE THAT YOU HAVE TO HAVE A TEAM OF PEOPLE BEFORE YOU START, SO THAT THE FUNDING AT THE OTHER END ISN'T SUCH A SCRAMBLE. >> WE HAVE KIND OF SEEN IT ALL. YOU HAVE INCENTIVE AS A TEAM TO MAKE SURE THAT WE NOW KNOW HOW TO ANTICIPATE THE COST GOING FORWARD. THE PATIENTS HAVE TO KNOW. AND WE HAVE BEEN CRITICIZED WE UNDERMINE THE NATURE OF OUR EXPERIMENTS BECAUSE PATIENTS HAVE TO HAVE A BUILT-IN SORT OF THERAPEUTIC MISCONCEPTION BECAUSE WE REQUIRE THEM TO PAY. IN CANCER TRIALS PEOPLE GET STANDARD OF CARE THEY PAY AND INVESTIGATIONAL DRUG WITH NO GUARANTY IT WILL WORK. THERE IS SOMETHING MAGICAL ABOUT DEVICES YOU KIND OF, TO ASSUME THAT RESPONSIBILITY IS DIFFERENT. THERE ARE THINGS THAT THE GOVERNMENT WHICH, KNOCK ON WOOD, WILL REMAIN IN PLACE. MEDICARE DOES HAVE A CLAUSE, IF YOU HAVE AN I.D.E. YOU CAN GO TO YOUR LOCAL MEDICARE AND YOU CAN APPLY FOR A MEDICARE ELIGIBLE PATIENT TO GET REIMBURSED AND IT'S PRETTY STRAIGHT FORWARD AND ONCE YOU HAVE THAT, THE PERSON HAS TO BE MEDICARE ELIGIBLE. YOU HAVE PEOPLE WITH INSURANCE. BECAUSE WE HAVE KIND OF TAKEN ADVANTAGE OF, BECAUSE WE HAVE THAT FOR THE MEDICARE ELIGIBLE, WE DON'T RESTRICT IT TO ONLY MEDICARE ELIGIBLE PEOPLE BUT BECAUSE WE HAVE THAT WE HAVE ARGUED WITH INSURANCE CARRIERS THAT -- AND NOW WE ARE TRYING TO COME UP WITH, WHAT IS THE COST OF BEING HOSPITALIZED, TWO COURSES OF E.C.T. THAT THE COURSE OF KEEPING PEOPLE WELL IS DIFFERENT. NOBODY IS INTERESTED. THEY WANT TO KNOW WHAT THEIR QUARTERLY COST WILL BE. AND IT'S A HARD SELL. BUT IF YOU WORK AT IT HARD ENOUGH, THE INSURANCE COMPANY PAYS. THAT'S A HUGE BURDEN FOR A RESEARCH TEAM. IT'S A HUGE BURDEN. AND THEN THE COSTS, IF SOMEONE HAS TO SELF PAY OR IF SOMEONE DOESN'T PAY. THE NIGHT BEFORE A SURGERY YOU DON'T WANT THE BILLING DEPARTMENT AT THE HOSPITAL CALLING YOU AND SAYING YOU WEREN'T APPROVED AND WE ARE CANCELING YOUR SURGERY. YOU HAVE TO NEGOTIATE WITH THE HOSPITAL TO ACTUALLY SAY PEOPLE SELF-PAY IF THEY WILL PAY THAT WAY IS GETTING THE MEDICARE RATE, THAT'S NEGOTIATING UP FRONT WITH YOUR HOSPITAL BEFORE YOU START, AND NOT EVERY HOSPITAL IS GOING TO DO THAT. THERE ARE THINGS YOU CAN'T KNOW UNTIL YOU KNOW YOU NEED TO CARE. WE HAVE HAD SOME PEOPLE THAT HAVE FALLEN THROUGH OR THEIR CIRCUMSTANCES CHANGED, THEY ARE DOING WELL, BUT NEED A BATTERY REPLACEMENT. WE HAVE BEGGED THE CHARITY FOR A BATTERY REPLACEMENT AND WE HAVE GOTTEN IT. I CONSIDER IT MY MORAL OBLIGATION TO FIGHT, IF WHAT YOU HAVE TO DO IS GUILT YOUR INSTITUTION, I CAN TAKE IT, AND I HAVE TO. BUT I CAN'T SPEAK FOR WHAT WILL HAPPEN -- I CAN'T EVEN SPEAK FOR WHAT WILL HAPPEN IN THE INSTITUTION. BUT I WILL TELL YOU, I'M MOVING IN ANTICIPATION OF MY NEW WORK KNOWING FROM ONE MODEL, PART OF MY START UP WAS I WANT X, THAT IF I HAVE A RESEARCH PROTOCOL AND I CAN'T GET THE P INSURANCE OR MEDICARE TO PAY AND I HAVE THIS SITUATION, I WANT YOU TO ABSORB THE COST OF THE SURGERY. THE INSTITUTION. AND I HAVE THAT IN WRITE K. WRITING. BUT MY COLLEAGUES, MY TEAM, A SURGEON WHO EXPECTS TO GET PAID. MY SURGICAL COLLEAGUE WILL HAVE TO AGREE TO THAT AS WELL. BUT THE HOSPITAL COSTS ARE WHERE THE EXPENSE IS NOT -- THE DEVICES ARE BECOMING EXPENSIVE. >> DO OTHERS WANT TO RESPOND TO THIS? >> I WILL JUST BE REALLY QUICK. HELEN DOES AN AMAZING JOB BUT ONE OF THE WORRIES, OF COURSE, -- DO NOT DO THIS. THIS IS A BURDEN. YOU DO NOT WANT. >> MAYBE NOT EVERYBODY ELSE CAN DO IT OR WOULD DO IT SO IT SEEMS THEN WE HAVE TO HAVE SOME KIND OF STRUCTURE AT THE GET-GO. I DON'T KNOW, I THINK EMPIRICALLY, I DON'T KNOW WHAT THE AMOUNTS WOULD BE OR IF IT'S EVEN FEASIBLE TO SAY, WE WILL COVER THIS GROUP OF PEOPLE FOR REALLY AN INDEFINITE PERIOD OF TIME. >> CHRISTINA, THIS IS CARLOS PENA, F.D.A. OKAY. >> I THINK GOING THROUGH THIS PROCESS, MACHADO HAD NO IDEA SOME WAS SOMETHING HE WAS GETTING INTO AT FIRST. AND HELEN, AS YOU MENTIONED, IT BECAME THIS THING. THERE WAS NO PRIMER, THESE WERE THE THINGS TO EXPECT. EVEN THE CLEVELAND CLINIC THAT HAS ANCILLARY RESOURCES, IT WAS UNEXPECTED. I THINK BECAUSE YOU GO THROUGH SEPARATE PROCESSES TO GET THE FUNDING. AND THERE ARE SO MANY DIFFERENT AVENUES PUTTING THAT TOGETHER IS DIFFICULT AND TRYING TO SAY WHAT WILL HAPPEN WITH THIS KIND OF STRUCTURE YOU PUT TOGETHER, LONG TERM IS EVEN HARDER TO SAY. >> CARLOS AND THEN PAUL. >> SURE. I THINK THIS IS A GOOD AREA TO TALK ABOUT NEURO ETHICS. FROM AN F.D.A. PERSPECTIVE, WE SEE ACCESS TO DEVICES BY PATIENTS IN A NUMBER OF WAYS. THERE IS THE PRACTICE OF MEDICINE WHERE WE DON'T HAVE INVOLVEMENT IN A DISCUSSION BETWEEN PHYSICIAN AND PATIENT, FROM COMPASSIONATE USE, TO HUMANITARIAN USE, TOVATIONAL USE. -- INVESTIGATIONAL USE. THERE ARE A NUMBER OF WAYS A PATIENT CAN GET ACCESS TO A DEVICE. THAT ACCESS NEEDS TO BE TAILORED, THE INFORMED CONSENT NEEDS TO BE TAILORED BECAUSE EACH PATHWAY HAS UNCERTAINTY. HUMANITARIAN. WE WOULD EXPECT A LOT MORE SAFETY AND EFFECTIVENESS IN PIVOTAL STUDY BECAUSE WE KNOW WHAT WE ARE POTENTIALLY STUDYING. VERSUS COMPASSIONATE USE. ONCE THE DEVICE GETS OUT THERE, REGARDING POST-TRIAL CONSIDERATIONS, A DEVICE, SOME DEVICES COME OUT. THEY HAVE A NICE GREAT SET OF DATA. SAFETY AND EFFECTIVENESS DATA. THERE ARE OTHER DEVICES WE HAVE ASKED FOR THREE PLUS POST-APPROVAL STUDIES. WE HAVE POST APPROVAL REQUIREMENTS IN PLACE. MY QUESTION TO THE PANEL, HOW CAN WE MAKE SURE OUR PATIENTS AND INVESTIGATORS KNOW ABOUT THESE DIFFERENT TYPES OF STUDIES WHERE THE PATIENTS' EXPECTATIONS NEED TO BE GRADED TO WHAT THEY EXPECT PRE-MARKET AS WELL AS POST-MARKET. IF THEY ARE IN A HUMANITARIAN STUDY, THE POST MARKET OUT COMES WILL BE LIMITED. >> I WILL COMPARE THIS A LITTLE TO THE RISE, I WILL DO THIS BECAUSE IT'S SOMETHING I DO EVERYDAY AS WELL, IS THE RISE OF TRAUMA SYSTEMS. THERE'S AN INTEGRATION THAT HAPPENED WITH THE RISE OF TRAUMA SYSTEMS THAT ALLOWED FOR A LOT OF THIS DOWNSTREAM STUFF TO HAPPEN WITH MONITORING AND OUT COMES. YOU HAD INITIALLY IN THE 60'S AND 70'S PLACES THAT DIDN'T DO THIS IN A SPECIALIZED WAY. SOME WOULD GET TO A REHAB FACILITY, SOME WOULD GET SURGERY IN A TIMELY FASHION, WHO KNOWS. WITH THE RISE OF CREATING TRAUMA SYSTEMS YOU HAVE AN UNDERSTANDING THERE ARE CERTAIN PLACES THAT HAVE CAPACITY AND ABILITY TO FOLLOW PATIENTSTHAT ALLOWS THEM TO DO THIS WORK WELL IN A COMPREHENSIVE WAY. FROM ACUTE CARE TO LONG TERM FOLLOW-UP, REHABILITATION, TO SOCIAL WORK NEEDS AND EVERYTHING THAT IS REQUIRED. SOME WAYS, ESPECIALLY DOING THIS PROJECT WITH MACHADO, YOU SEE SIMILAR THINGS HAPPENING LIKE 40 YEARS AGO WITH DEVICE DEVELOPMENT. WE HAVE A LOT OF WAYS OF DEALING WITH IT BUT IT HASN'T BEEN INTEGRATED VERY WELL AND THERE ISN'T A QUALITY PROCESS HOW WELL ARE WE DOING. NOW YOU HAVE TO MEET CERTAIN BENCHMARKS OF OUTCOMES, LENGTH OF STAY, RISK. YOU HAVE THE AMERICAN COLLEGE OF SURGEONS COME VERIFY HOW WELL YOU ARE DOING. THERE COULD BE CRITICISMS AS WELL. THERE PROBABLY NEEDS TO BE SOMETHING SIMILAR IN PLACE FOR DEVICES. THERE'S A STRONG CONNECTION BETWEEN THOSE WHO IMPLANT THE DEVICES AND THOSE WHO CARE FOR THEM AND THE PATIENTS AND IT'S PROBABLY DIFFERENT FOR PHARMACEUTICALS THOUGH YOU CAN MARK ARGUMENTS EITHER WAY. THERE'S NO SYSTEM HOW CAN WE DO BETTER. HOW DOES IT DIFFER WITH DISEASE OR DEVICE. AND I THINK THAT'S BEEN HARMFUL IN A WAY. >> I WAS TRYING TO THINK ABOUT, I AM GLAD YOU SAID THAT. I THINK BASED ON CARLOS'S QUESTION, YOU HAVE A RESPONSIBILITY OF THE PEOPLE WHO DID MAKE THE DEVICE. SOMETIMES IT'S THE SPONSOR THEMSELVES. AND YOU ARE TRYING TO THINK, YOU HAVE THE RESPONSIBILITY OF WHO PAID FOR IT AT ONE LEVEL, SO IF IT'S INVESTIGATOR INITIATED YOU HAVE AN ISSUE. BUT AS YOU WERE SAYING WITH LEE HOCHBERG, YOU HAVE A GRANT, IT HAS A RANGE OF TIME. IT'S LIKE, NO OFFENSE, SINCE YOU ARE THE HOST AT N.I.H., BUT IT DOES BRING UP A RELATED ISSUE, YOU GET A GRANT AND THERE'S AN OBLIGATION WHEN YOU SIGN FOR THAT MONEY THAT YOU WILL PROVIDE ACCESS FOR LONG TERM ACCESS TO SHARE YOUR DATA. AND YOU DON'T HAVE A PLAN. I'M SUPPOSED TO SHARE MY DATA FOR HOW LONG, WITH WHOMEVER PAST THE TIME I HAD THE GRANT AND HOW AM I GOING TO PAY TO HOST THAT AND HAVING THIS EXPERIENCE WITH IMAGING DATA THAT'S A WHOLE OTHER RESPONSIBILITY I DIDN'T SIGN UP FOR OR COULD HAVE ANTICIPATED. SO WE ARE OUR NUCLEUS INCUMBENTS WE HAVE SHORT-TERM RESCHEDULING, WE DON'T LIKE HAVING TO ANTICIPATE THINGS MANY YEARS DOWN THE LINE. BUT I WAS VERY HORRIFIED TO HEAR WHAT LEE SAID, ABOUT THE NOTION OF I HAVE MY GRANT AND WHAT WE ARE GOING TO DO, HE WORRIES ABOUT IT. WHEN I THINK ABOUT IT, I'M INSANE. I GET THESE GRANTS. HE HAVEN'T EVEN HAD N.I.H. FUNDING. I JUST KEEP GETTING THEM AND ROLLING THEM. THEY SUPPORT MY TEAM. I'VE GOT PEOPLE TO PROVIDE SUPPORT SYSTEM. AND THAT'S HOW I END UP DOING IT. THAT IS NOT A VIABLE MODEL FOR ANYTHING. IF I RETIRE, OR GET HIT BY A BUS WHO WILL PAY FOR THAT SUSTAINABILITY MODEL. IT WON'T MATTER TO ME BUT -- THERE IS THAT, NO JOKE. THERE IS THAT SENSE OF, WE DON'T HAVE A PLAN. I WILL EVEN SAY YOU WRITE A GRANT AND TALK TO YOUR OWN HOSPITAL, YOU HAVE MONEY TO PAY FOR THE SURGERY. YOU HAVE EVEN BUNDLED IT IN, YOU MADE THE CALCULATION AND HAVE THE AMOUNT. SO I SAID TO MY HOSPITAL, IF SOMETHING GOES WRONG ON THE TABLE AND I HAVE TO HAVE THE PATIENT IN THE HOSPITAL BECAUSE THERE'S A CATASTROPHIC EVENT, CAN I PLEASE BUY CATASTROPHIC INSURANCE FOR EACH OF MY PATIENTS. WHEN I FIRST GOT TO EMERY THEY SAID YOU CAN'T DO THAT. I SAID WHY NOT. ONE CATASTROPHE OF ONE PATIENT OF STUFF COULD HAPPEN, WITH THE BEST SURGEON, WIPES OUT ALL THE MONEY I HAVE GOT FOR THE GRANT. WE WILL DEAL WITH IT WHEN IT HAPPENS. THE TRUST ME MOTTO. I THINK THAT THE MODELS, BECAUSE WE ARE AT N.I.H. WITH 80 PEOPLE WITH THESE GRANTS. AND YOU KNOW, MANY OF THESE THINGS IT WILL YIELD INTERESTING INFORMATION AND THESE ARE MOOT POINTS BUT IN THIS OTHER SPACE WE ARE ALREADY THERE, MAYBE WE LEAVE AND DON'T HAVE A PLAN EXCEPT YOU HAVE TO KNOW IN ADVANCE AND PROGRAM HAS TO BE ANTICIPATING THERE'S A MODEL AND YOU HAVE TO BE WILLING TO PAY FOR IT TOO. BUT PATIENTS HAVE TO LEARN HOW TO -- IF THEY SHOULD GET LUCKY ENOUGH TO HAVE BENEFIT, THAT THEY PERCEIVE JUST LIKE IF THIS WAS HEALTH CARE. THAT NOT EVERYBODY GETS ACCESS TO EVERYTHING IF YOU CAN'T PAY. UNTIL WE FIX THAT, THEN DOING IT IN THIS MODEL IS SORT OF PIPE DREAM. >> OKAY. PAUL -- [OFF MIC] >> I WANT TO PUSH PATIENT OBLIGATION, HOW MUCH WOULD BE TOO MUCH PATIENT OBLIGATION POST BEING A RESEARCH SUBJECT. TO WHAT DEGREE CAN YOU BARTER, OR EXPECT OR OBLIGATE PATIENTS TO CONTINUE TO PARTICIPATE IN RESEARCH MEASURES AFTER THE END OF THE TRIAL, IN EXCHANGE FOR FOLLOW-UP? YOU MIGHT SAY I CAN FOLLOW-UP BUT I CAN ONLY JUSTIFY IF YOU AGREE TO DO THIS MANY SCANS AND THIS MANY NEURO PSYCH TESTS, IF YOU CAN DO THAT FOR ME, OR IS THAT COERCIVE OR UNDUE INFLUENCE, WHAT IS THE BOUNDARY WHERE WE HAVE COMMITTED TO THEM BUT THEY HAVE TO COMMIT TO US TOO FOR THE RESEARCH FOR THIS RECIPROCITY TO OCCUR? >> I THINK IT'S A GREAT QUESTION. I DON'T KNOW IF I HAVE AN ANSWER READY. I WOULD WORRY, AS YOU HINTED AT IF THERE'S THIS TIT-FOR-TAT MODEL, I KNOW YOU MAY NEED UPKEEP, IF YOU WANT IT YOU WILL IS TO PAY TO PLAY, ESSENTIALLY. IT'S A KIND OF CUTTING LOOSE. IN OUR STUDIES WE TELL PEOPLE YOU CAN STOP WHEN YOU WANT. RIGHT? THIS IS PART OF GOING THROUGH THAT INFORMED CONSENT PROCESS. AND HAVING YOUR AUTONOMY RESPECTED. YOU CAN'T STOP HAVING THE DEVICE IN. ALTHOUGH EVEN THERE IT SEEMS WE DO TYPICALLY INCLUDE THE OPPORTUNITY FOR EXPLANT. BUT YEAH, I GUESS I DO WORRY THERE'S A LITTLE BIT OF, WELL NOW I'M DONE WITH YOU, UNLESS YOU ARE WILLING TO PAY ME MORE. GIVE ME SOMETHING ELSE. >> WE DO SCANS AND BRING PEOPLE BACK BUT YOU KIND OF HAVE YOUR NON-NEGOTIABLE TERMS FOR THE TRIAL WHEN YOU HAVE THESE EXTRA MEASURES. I THINK THE ISSUE COMES, FOR AN I.D.E. YOU NEED ROUTINE REPORTING. YOU NEED TO KNOW IF IT'S CONTINUING TO BE EFFECTIVE, CONTINUING TO BE SAFE. SO IT ISN'T JUST A RESEARCH AND WE WANT TO DO STUFF TO YOU AND LEARN STUFF. IT'S ACTUALLY PART OF OUR OBLIGATION FOR HAVING ACCESS TO AN INVESTIGATIONAL OR IMPROVED DEVICE TO ENSURE THE PATIENT IS SAFE. PATIENTS UNDERSTAND THAT, IF I'M DOING WELL, YOU COME BACK EVERY SIX MONTHS, OR EVERY YEAR. THEY WANT TO SEE US. BUT PEOPLE COULD TRAVEL SO IT COULD BE DIFFICULT. YOU HAVE YOUR MEASURES, YOU TRY NOT TO MAKE THEM ONEROUS. YOU ASK THEM IF THEY WANT AN E.E.G. WHEN PEOPLE ARE DOING WELL THEY TEND TO WANT TO BE HELPFUL BECAUSE THEY HAVE EVOLVED TO BE GRATEFUL. HOWEVER WHEN YOU ARE NOT DOING WELL YOU WANT IT OUT OF ME, NICE TO KNOW YOU AND I HOPE YOU ARE OKAY. I THINK THE ISSUE IS I DON'T FIND IT COERCIVE FOR THE RESEARCH PART BUT I HAVE HAD SITUATION, WHERE SOMEONE WAS DOING WELL. JUST HAD TO DRIVE A COUPLE HOURS AND DECIDED, I'M DOING OKAY, WHY DO I NEED TO COME AND HAVE THOSE STUPID RATING SCALES. I DON'T WANT TO DO IT. WE KIND OF TRY TO EXPLAIN WHAT THE REPORTS WAS. IT'S LIKE WHAT ARE YOU GOING TO DO TO ME IF I DON'T COME IN. IT'S LIKE I'M NOT GOING TO DO ANYTHING TO YOU BUT WHEN YOUR DEVICE DIES AND YOU ARE LIKELY TO GET ILL, YOU ARE GOING TO EXPECT US TO NOW COME IN AND REPLACE YOUR BATTERY. SO PART OF THAT IS A RECIPROCAL LEVEL OF RESPONSIBILITY. WE DON'T WANT TO BE ONEROUS. I'M NOT THREATENING YOU BUT WHEN THAT DEVICE, YOU CAJOLE AND YOU EXPLAIN AND IT'S OKAY WITH ME IF YOU WANT TO WAIT BUT UNDERSTAND OUR POSITION. AND EVENTUALLY KIND OF CAME AROUND AND ONCE GOT THE RECHARGEABLE DEVICE AND IF HE DOESN'T WANT TO COME IN, GET THE MEASURES. I THINK OVER TIME, THE LONGER PEOPLE ARE WELL, IT BECOMES A MATTER OF REPORTING OBLIGATION TO THE F.D.A. AND THE GOAL IS TO MAKE PATIENTS FEEL RESPONSIBLE THEY ARE HELPING US TO HELP THEM. >> KATRINA? >> I THOUGHT ONE THING THAT MIGHT BE RELEVANT TO THAT QUESTION IS WHO BENEFITS. WHO IS CONDUCTING THE TRIAL OR PAYING FOR THE TRIAL, WHO HAS THE DATA, WHO HAS ACCESS TO IT AND WHAT'S BEING WITHHELD. I GUESS IF IT'S AN INDUSTRY-SPONSORED TRIAL AND THEY HAVE A LOT OF INTEREST IN THE DATA, AND WHAT'S BEING WITHHELD IS KIND OF SUPPORT THAT THE PATIENT IS VERY VULNERABLE TO, THAT MAY BE A DIFFERENT SITUATION TO MAYBE YOUR TRIAL WHICH MAY BE MORE RESEARCH LEAD OR SOMETHING LIKE THAT. SO I THINK THAT MIGHT BE RELEVANT. WE THOUGHT A LITTLE BIT IN OUR PROJECT ABOUT MAINTENANCE CONTRACTS AND HOW COERCIVE MAINTENANCE CONTRACTS MAY BE. WE THINK OF PARALLELS WITH CARS WHERE YOU MAY BE LOCKED IN TO GOING TO THE GENUINE PARTS OR SOMETHING LIKE THIS. IT'S NOT QUITE THE SAME, BUT I THINK THERE ARE QUESTIONS THAT ARISE JUST WITH CONSUMER PRODUCTS ABOUT HOW YOU MIGHT VOID OR VIOLATE YOUR WARRANTY OR SOMETHING. THAT SEEMS TO BE SORT OF RELATED TO THIS QUESTION AND MIGHT BE USED AS ANALOGOUS TO SHED LIGHT ON THE ANSWER. >> ONE THING I ASKED LEAH ABOUT REVERSE COMPATIBILITY. IF YOU HAVE THE INVESTIGATIONAL PRE-MARKET OF A DEVICE AND NOW WE HAVE BOSTON SCIENTIFIC, WE HAVE SAINT JUDE. IF YOU ARE WORKING WITH MEDTRONIC AFTER THE D.B.S. YOU ARE REPURPOSING A STANDARD APPROVED DEVICE. EVEN IF A TRIAL FAILED, YOU COULD GET ACCESS AND THE QUESTION IS HOW TO PAY. THE EQUIPMENT IS THERE. THE EQUIPMENT, YOU COULD PLUG IT INTO SOMETHING ELSE, THE BATTERIES CHANGE. SO IF YOU ARE USING AN UNAPPROVED DEVICE THAT THEN BECOMES APPROVED BUT THEN THEY UPGRADE THE DEVICE, IS YOUR DEVICE GOING TO BE REVERSE COMPATIBLE? IT TURNS OUT THAT THE SAINT JUDE DEVICES, I LEARNED THAT BY ASKING. I DIDN'T EVEN KNOW IT. IT COULD BE WHEN SOMEONE NEEDED SOMETHING REPLACED WE COULD BE BACK COMPATIBLE. BUT THERE IS THE ISSUE OF COMPANIES WHO ARE GOING TO, YOU KNOW, THE COMPANIES SPEND A LOT OF EFFORT WITH N.I.H. EVERYONE WAS COMPLAINING FIVE YEARS AGO THAT THE COMPANIES RESEARCHERS HOSTAGE. THE COMPANIES WEREN'T MAKING THE FINANCIAL INVESTMENT AND EVEN IF YOU WANTED TO JUST BUY IT THEY COULD VETO YOUR IDEA BECAUSE THEY WERE WORRIED WHAT IT WOULD DO TO THEIR REPUTATION AND EVERYBODY NEGOTIATED. [INAUDIBLE] WAS INVOLVED IN THAT WHERE YOU PUT ALL THE DEVICES IN A POT, N.I.H. BECOMES ARBITRATOR OF WHAT'S GOOD SCIENCE OR NOT AND COMPANIES HAVE RIGHT OF FIRST REFUSAL. IT'S KIND OF HANDLED BUT YOU STILL HAVE THIS NEW DEVICE SITUATION. AND COMPANIES ARE GOING TO NEED TO THINK IN THIS SPACE ALSO AS THEY BUILD THINGS, HAVING THIS COMPATIBILITY SO THAT I WONDER IF THE DEVICE MANUFACTURERS THEMSELVES IF THEY ARE USING DEVICES IN EXPERIMENTS, IT'S NOT TO PUT IT ONTO THEM BECAUSE THEY HAVE THE DEEP POCKETS. BUT IN THIS SPACE RIGHT NOW OF WHERE WE CURRENTLY STAND AS A TEST PRINCIPLE, THAT IF YOU HAVE GIVEN YOUR DEVICES TO BE AN N.I.H.-RELATED TRIALS OR EXPERIMENTS OF THIS TYPE, THEN YOU ACTUALLY HAVE AN OBLIGATION TO HELP WITH THE REGISTRY. N.I.H. HAS NOT STEPPED UP TO SAY WE WILL DO THE REGISTRY. SO THAT WOULD BE NICE AND APPROPRIATE BUT I UNDERSTAND WHY NOT. AT SOME LEVEL THAT WOULD WORK FOR YOUR REPORTING LONG TERM TO THE F.D.A. THERE ARE PEOPLE AND YOU HAVE AN R 24 IN THE BRAIN INITIATIVE TRYING TO DEVELOP PLATFORMS WHICH DATA IS SHARED. AND PLATFORMS DATA IN WHICH PEOPLE HAVE COME UP WITH A WAY TO SHARE THE PLATFORMS, NOT TRY TO REINVENT THE WHEEL AND HAVE THINGS THAT WORK FOR F.D.A., INVESTIGATORS SHARING. INSTEAD OF EVERYBODY COMPETES WITH EACH OTHER TO REINVENT THE WHEEL AND WE HAVE NOTHING THAT ANYBODY CAN USE, THAT SOMEONE STEPS UP AND SAYS LET'S ALL TRY USING THIS AND IF SOMEONE BUILT A PLATFORM THAT IS VERSATILE WE CAN BUILD SOMETHING TOGETHER. I THINK THERE NEEDS TO BE SOME GROUP SPEAK ON THIS. >> THANKS. THIS HAS BEEN REALLY INTERESTING THINKING OF ALL THE BROADER IMPLICATIONS OF THIS. I ASSUME A NUMBER OF THESE DEVICES BECOME OBSOLETE, THAT THERE ARE UPGRADES, WHETHER IT'S NEWER DEVICES WITH BETTER BATTERIES, BETTER FUNCTIONS, ETC. WHAT DOES THAT LOOK LIKE? AND WHAT ARE THE OBLIGATIONS WITH RESPECT TO RESEARCH SUBJECTS FOR UPGRADES AS THEY BCOME AVAILABLE OR THEIR DEVICE BECOMES OBSOLETE IS ANOTHER WAY OF ASKING THE QUESTION AS WELL. I ASSUME SOME OF THESE LIKE ANY OTHER TECHNOLOGY BECOME OBSOLETE OVERTIME. YOU CAN NO LONGER GET SUPPORT FOR CERTAIN TYPES OF DEVICES. I WONDER IF THE SAME THING IS NEEDED FOR BRAIN IMPLANTS. IF YOU COULD SPEAK TO THE BROADER KIND OF UPGRADE ISSUES AS WELL. >> THE SAME DEVICES IN PEOPLE THE ENTIRE TIME. I THINK ONE OF THE SURGEONS, YOU'RE NOT OLD ENOUGH. THE ISSUE IS, SINCE 1997, MEDTRONIC INTRODUCED THE P.D. DEVICES. THAT'S A TRAGEDY, THAT'S WHY THERE'S A BRAIN INITIATIVE. IT'S THE SAME BASIC DEVICE. I DON'T KNOW THAT YOU CAN PLUG IN A CONNETRA TO ANOTHER THING. YOU MAY NOT BE ABLE TO. PEOPLE HAVE TRIED TO COME UP WITH WAYS TO HAVE ADAPTORS. BUT IN FACT WE HAVEN'T GOTTEN THAT MUCH SMARTER YET TO BE ABLE TO ACTUALLY SAY THE DEVICE IS OBSOLETE. THAT'S WHY THE STEP-WISE PROGRESSION OF HAVING A STIM AND SENSE DEVICE, THAT'S AN ITERATIVE. I THINK IT BRINGS UP MAYBE ONE OF THE SURGEONS KNOWS? >> I WOULD BE HAPPY TO JUMP IN. >> KATRINA? >> SORRY. >> WE LOOKED AT PACEMAKERS AS A CASE STUDY AND THEY EMERGED SLOWLY IN THE 60'S AND EVOLVED QUITE A LOT OVER TIME. THERE WAS A QUESTION WE HAD WHAT HAPPENS WHEN THE PULSE NEEDS TO BE REPLACED WHAT IF YOU GET A DIFFERENT BRAND BECAUSE IT'S SAFER TO PULL OUT THE BATTERY THAN THE LEADS. THAT BECAME A PROBLEM OVER TIME. SO ABOUT 30 YEARS OR SO INTO THE LIFE OF THE PACEMAKER IT WAS SUCH A PROBLEM THEY GOT TOGETHER AND ESTABLISHED A STANDARD FOR ADAPTORS SO THERE WAS HIGHER EXPECTATIONS OF BACKWARDS COMPATIBILITY AND CROSS-DEVICE COMPATIBILITY. WHICH I THINK ADDRESSES SOME OF THESE CONCERNS ABOUT OBSOLESCENSE. IT GIVES RISE TO OTHER ISSUES BECAUSE IF YOU CHANGE PLATFORMS THERE MAY BE A DEBATE WHOSE BIT FAILED. IF YOU HAVE MEDTRONIC PACEMAKER AND ANOTHER LEAD, THERE MAY BE A DISAGREEMENT WHICH IS THE THING THAT IS THE CAUSE OF THE FAILURE AND THAT MAY CAUSE PROBLEMS IN FOLLOW-UP. THE OTHER THING I FOUND OUT JUST THE PROCESS OF MAKING STANDARDS WAS REALLY QUITE COMPLICATED AND IN SOME WAYS QUITE ANSWERABLE TO GROUPS DOMINATED BY INDUSTRY, WHICH THINGS GOT A STANDARD, SOMETIMES BECAUSE THERE WAS A REAL CLINICAL ISSUE LIKE WITH THE BACKWARDS AND CROSS-PLATFORM CAPABILITY. BUT SOMETIMES THERE WERE REASONS THAT DIDN'T MAKE SO MUCH SENSE. >> I COULD SPEAK AT LEAST TO DEVICES BROADLY WITHIN NEURO SURGERY. THERE'S ACTUALLY COMMERCIAL INCENTIVE TO FIGURE OUT HOW TO FIX OBSOLETE DEVICES. SHUNT TECHNOLOGY, YOU MAY HAVE PUT IN A SYSTEM THAT IS 20 YEARS OLD AND NOW A PERSON WHO HAS A NEW PROBLEM, MAYBE ADJACENT TO THE PROBLEM BEFORE, SPINE FUSION FOR EXAMPLE. COMPANIES ARE INTERESTED, THEY HAVE FOUND A WAY TO MAKE THEM COMPATIBLE, SO THERE IS INCENTIVE BUILT INTO JUST THE INNOVATION DEVICE WORLD. OUTSIDE OF A RESEARCH CONTEXT. SOME OF THE CONCERNS ABOUT A DEVICE BECOMING OBSOLETE ARE ACTUALLY FIXED BY NATURE OF DEVICE GENERATION ITSELF, THERE ARE PEOPLE WHO WANT THEIR PRODUCT TO TALK WITH THE OLDER ONE AND IT HAPPENS NATURALLY IN THE DEVICE WORLD. AS FAR AS -- >> [INAUDIBLE] >> THERE'S NOT MUCH INTERCHANGABILITY. >> WE HAVE THE CONNECTION WITH DIFFERENT ADAPTORS AND WE HAVE A MEDTRONIC HEADER THAT GOES ONTO OUR BATTERY THAT WE CAN ACTUALLY GO AND HAVE MEDTRONIC EXTENSIONS INTO OUR BATTERY. BUT WE ARE THE ONLY COMPANY AT THIS TIME THAT DOES THAT. >> ALL RIGHT. SO THE LAST QUESTION IN THE BACK. SORRY WE HAD TO TAKE THE MIC FROM YOUR HANDS. >> I REITERATE WHAT ANDRE MACHADO SAID ABOUT THE UNFORESEEN. WHEN YOU GET INTO THE DEVICE UNDOING DEVICE THERE WILL BE UNFORESEEN THINGS THAT WILL HAPPEN NO MATTER WHAT YOU ARE DOING. YOU SHOULD TRY TO LEARN FROM THE OTHER PAST EXPERIENCES WHETHER IT'S BEEN HELEN'S WISDOM OR THE EXPERIENCE PARKINSON'S, ALZHEIMER'S, 20-30 YEARS EXPERIENCE. BUT YOU WILL STILL GET ALL THIS UNFORESEEN STUFF AND YOU WILL HAVE TO BE PREPARED IN SPITE OF EVERYTHING DESPITE THINKING ON YOUR FEET AND COMING UP WITH SOLUTIONS. THERE WILL BE ALL KINDS OF STUFF THAT HAPPENS. NO ONE CAN TELL YOU WHAT IT'S GOING TO BE. THE OLD ADAGE IT'S EASIER TO GET INTO THINGS THAN GETTING OUT OF THEM. RINGS VERY, VERY TRUE HERE. AND CERTAINLY, NEURO SURGERY, ONCE WE GET INVOLVED WE ARE MARRIED TO OUR PATIENTS. THEY BELONG TO US. AND AS FAR AS SOCIETY IS CONCERNED YOU OWN THEM. THAT'S JUST THE WAY IT IS. AS YOU GET INTO YOUR PROJECTS NO MATTER WHAT THEY ARE, JUST PREPARE IN YOUR MIND LIKE OTHER THINGS YOU WILL FIND YOURSELF IN SITUATIONS WHERE LIKE, WOW I NEVER EXPECTED THIS WAS GOING TO HAPPEN. YOU KNOW WHAT I MEAN? AND YOU KNOW -- AND YOU WILL HAVE TO DEAL WITH IT AND HAVE A TEAM WHERE YOU SIT DOWN AND TRY TO COME UP WITH SOLUTIONS BECAUSE IT JUST HAPPENS CONTINUOUSLY IN THE PAST AND IT WILL CONTINUE TO HAPPEN IN THE FUTURE. >> I THINK PART OF IT IS WE DON'T LIKE TO BE PESSIMISTS WE GO INTO IT THINKING THERE WILL BE BENEFIT BUT YOU WANT TO THINK WHAT HAPPENS IF THERE'S A CATASTROPHIC EVENT IN THE SURGERY. THINKING UP FRONT, WE WON'T KNOW ALL OF THEM BUT BEING SOME WAY PREPARED. I DON'T KNOW HOW WE PAY FOR IT BUT SEEMS THAT'S THE ATTITUDE WE HAVE TO HAVE. >> HOW DO WE SET UP TO ACHIEVE GOOD THINGS. PART IS DISCOVERING WHERE AND HOW TO FIND GOOD THINGS. ONE IS YOU LEARN AND YOU TRY TO MAKE IT BETTER AS YOU GO ALONG. LTS NOT JUST SETTING UP THE PERFECT FRAMEWORK. IT'S ITERATIVE. I THINK IT COULD BE EXCITING FOR ETHICS TO THINK OF IT THAT WAY. HOW DO WE MAKE THESE THINGS BETTER. FROM THE SAME POINT AN ENGINEERING STANDPOINT BUT HOW DO WE MAKE THESE PROCESSES AND SYSTEMS BETTER TO GET THE OUTCOMES WE WANT. >> I WANT TO END ON AN OPTIMISTIC NOTE. GORDON'S COMMENT WAS TRUE AND I HARKEN BACK TO MY FIRST COLLEAGUE LOZANO, HE SAID IT'S JUST STARTING. WE HAVE A REASON TO PERSEVERE. WE DON'T KNOW WHAT KIND OF PROBLEM WE WILL RUN INTO BUT WE WILL BE THERE PREPARED TO DEAL WITH IT SO IF THE QUESTION IS WORTH IT YOU HAVE HIGH INCENTIVE YOU WILL WORK IT OUT. WHEN CLINICIANS DRIVE THESE PROCESSES, WE ARE USED TO THAT. PATIENTS HAVING TROUBLE. THAT'S WHY WE REALLY CAN'T SEPARATE THE CLINICAL FROM THE RESEARCH. YOU CAN PUT UP WALLS. YOU CAN MAKE DIDACTICS YOU CAN MAKE RULES OF EVIDENCE BASED. BUT IF YOU MORALLY AND CLINICALLY REMEMBER THAT OBLIGATION IT WORKS OUT. PEOPLE ARE ALWAYS RAGGING ON THE FACT WE ARE SUPPOSED TO BE SMARTER THAN WE CAN POSSIBLY BE. THE FIRST PACEMAKERS WERE BIG GIANT THINGS YOU WERE ATTACHED TO IN A HOSPITAL. AND SO THE PROGRESS THAT'S HAPPENED, YOU CAN SAY IT'S SLOW, BUT IT'S ACTUALLY KIND OF QUITE REMARKABLE. I THINK IF WE LEARN NOW WHICH THINGS CAN REALLY GO BAD AND ANTICIPATE IT FROM OUR COLLECTIVE EXPERIENCE, EVERY TIME SOMEONE HAS AN INNOVATION WE WILL BE PREPARED AND WE CAN WORK OUT THE MONEY. >> OKAY, THANK YOU VERY MUCH. [APPLAUSE] >> WE HAVE COME TO THE END OF QUITE A FULL DAY. EVERYBODY LOOKS AS TIRED AS I FEEL. I WANT TO SAY A COUPLE THINGS. I THOUGHT OF THIS TIME AS BOTH A BUFFER, IF WE RAN OUT OF TIME BUT ALSO FOR SUMMING UP. SO IT SOUNDS LIKE WE HAVE SOLVED THE PROBLEM, WE KNOW EVERYTHING ABOUT THE RISK, WE KNOW EVERYTHING ABOUT CONSENT, AND WHAT TO DO AT THE END OF THE TRIAL. WE WILL FIND THE MONEY, RIGHT? [OFF MIC] I DO THINK THE DISCUSSIONS WE HAVE HAD TODAY PUT A LOT OF IDEAS, AT LEAST IN MY HEAD, I HOPE EVERYBODY ELSE FEELS THE SAME WAY. AND WE WILL TRY TO SYNTHESIZE THIS AND SEE IF WE CAN COME UP WITH SOMETHING THAT IS MEANINGFULLY HELPFUL FOR PEOPLE NOT SITTING IN THE ROOM HEARING THESE CONVERSATIONS. SO THAT WILL BE OUR NEXT PLAN. I WANT TO ASK, IS THERE ANYONE IN THE ROOM WHO DIDN'T GET A CHANCE TO SAY SOMETHING, OR HAS SOMETHING ELSE THEY WANT TO ADD TO OUR DISCUSSION BEFORE WE ADJOURN? >> I'M INTERESTED IN FOLLOWING UP WITH PEOPLE. I KNOW THERE'S BEEN TALK THROUGHOUT THE DAY, HOW DO WE CONTINUE THIS CONVERSATION. THERE'S SO MUCH THAT CAME UP, OBVIOUSLY WE CAN'T ADDRESS ALL THIS TODAY. I'M INTERESTED IN FOLLOWING UP WITH PEOPLE HEARING IDEAS OR WHAT WOULD BE A GOOD NEXT STEP. WINSTON, IS HE STILL HERE? HE LEFT. HE WAS SAYING HE THOUGHT WE COULD HAVE A FOLLOW-UP WORKSHOP OF ETHICS OF INTEROPERATIVE NEURO HUMAN RESEARCH. SO VERY SPECIFIC TOPIC, THAT'S AN EXAMPLE OF SOMETHING, WE COULD SPEND A WHOLE DAY TALKING ABOUT THAT. I WOULD LOVE TO HEAR FROM PEOPLE WHO ARE HERE, WHAT DO YOU THINK WOULD BE HELPFUL AS A NEXT STEP, WHETHER IT'S A GAP AREA OR SOME KIND OF DIFFERENT GROUP OF STAKEHOLDERS THAT NEEDS TO COME TOGETHER, STUFF LIKE THAT. SO PLEASE FOLLOW-UP. >> AND YOU CAN DO THAT BY? >> EMAIL. I THINK EVERYBODY HAS MY EMAIL ADDRESS BUT IF YOU DON'T, LET ME KNOW. >> ANYTHING ELSE? LAST COMMENTS. THIS WAS, AS WALTER SAID THIS MORNING, A DEEP DIVE INTO ONE ISSUE. THERE ARE LOTS OF OTHER ISSUES THE DIVISION HAS TALKED ABOUT AND ALL OF YOU KNOW ABOUT, BUT WHAT KHARA SUGGESTED THERE'S A DEEPER DIVE. I WANT TO SAY THANK YOU ALL FOR BEING HERE. I THINK IT WAS A REALLY USEFUL DAY. I HOPE YOU ALL FOUND IT TO BE. AND UNLIKE MOST OF THE TIMES YOU COME TO THE N.I.H. WE WILL END WITH THE OPTION TO HAVE WINE AND CHEESE IN THE BACK OF THE ROOM. SO PLEASE FEEL FREE TO CONTINUE THOSE DISCUSSIONS OVER SOME WINE AND CHEESE, AND THANK YOU AGAIN FOR COMING.