WE'RE PLEASED TO HAVE DR. JOE BONNER WHO IS GOING TO BE DISCUSSING PATHWAYS TO PREVENTION INITIATIVE AND GIVING US AN UPDATE. DR. BONNER. >> GOOD MORNING, EVERYBODY. WELCOME BACK. (INAUDIBLE) NCMRR, THAT IS THE NIH PATHWAYS TO PREVENTION WORKSHOP ENTITLED TENANTS OF PHYSICAL ACTIVITY TO HELP IMPROVE (INAUDIBLE). THIS EFFORT FIRST CAME ON YOUR RADAR IN MAY OF 2017 WHEN I APPROACHED THE BOARD (INAUDIBLE). IT'S EVOLVED AND TAKEN SHAPE OVER THE INTERVENING YEARS. AND SOME OF THAT I WAS DISCUSSING AT THE TIME AND SOME NOT, SOME WAS CONFIDENTIAL. TODAY I CAN FINALLY PULL BACK THE VAIL AND SHARE DETAILS THOUGH THERE ARE SOME SECRETS. WHAT'S NOT SECRET IS THAT THE DATE AND LOCATION, SO IT WILL BE THE WORKSHOP WILL BE HELD MARCH 30th AND 31st, 2020 AT THE NATCHER CONFERENCE CENTER ON NIH MAIN CAMPUS. AND BELOW THERE YOU CAN SEE HOW TO REGISTER. YOU CAN GO TO THE OFFICE OF DISEASE PREVENTION WEBSITE AT PREVENTION.NIH.GOV, IT'S LOCATED THERE, YOU CAN FIND THE REGISTRATION LINK AND IT WILL BE VIDEOCAST REMOTELY AT VIDEOCAST@NIH.GOV. ONE THING WE'RE VERY PROUD OF IS WITH SOME PREVIOUS WORKSHOPS, THAT HAVE BEEN HELD IN NATCHER, THERE IS DIFFICULTIES HAVING ENOUGH SPACE FOR PEOPLE TO USE WHEELCHAIRS TO COME AND ATTEND AND PARTICIPATE. WE HAVE GOT THE CONFERENCE CENTER TO REMOVE THE FIRST THREE ROWS OF SEATS, IN THE AUDITORIUM SO THERE'S AMPLE SPACE FOR PEOPLE WHO NEED A WHEELCHAIR. THIS IS APPARENTLY WHAT THEY DO FOR THE PRESIDENT WHEN THE PRESIDENT COMES TO SPEAK THEY REMOVE THEM FOR SECURITY REASONS. SO YOU CAN THINK OF IT AS THIS WORKSHOP WILL BE GETTING THE PRESIDENTIAL TREATMENT. I PERSONALLY THINK OF IT AS THE PRESIDENT GETS NCMRR TREATMENT. TODAY I WILL TALK ABOUT THESE FIVE POINTS REALLY. I WILL GIVE A BRIEF INTRODUCTION O THE PROGRAM, IT'S KIND OF COMPLEX SO I WILL WALK THROUGH IN STAGES. I WILL DESCRIBE THE SELECTED TOPIC AND THE STRUCTURE OF THE PATHWAYS TO PREVENTION PROGRAM. THEN I'LL GO INTO OUR PARTNERS. AND WE HAVE MANY PARTNERS ON THIS AND FINALLY THE DELIVERABLES THAT WILL BE PRODUCED BY THE CONCLUSION OF THIS THREE YEAR EFFORT. SOME OF THIS WILL BE REPETITIVE FOR BOARD MEMBERS THAT HAVE BEEN HERE A WHILE BUT SINCE WE HAVE NEW MEMBERS ON BEHALF OF PEEP ON VIDEOCAST I THOUGHT IT WAS IMPORTANT TO RECAP SOME OF THAT INFORMATION. SO THE PATHWAYS PREVENTION PROGRAM IS SPONSORED BY THE OFFICE OF DISEASE PREVENTION, WHICH IS LOCATED IN OFFICE OF DIRECTOR, THE NIH DIRECTOR, SO THAT'S FRANCIS COLLINS OFFICE. AND ON HERE YOU SEE HOW THE PATHWAYS OFFICE OF DISEASE PREVENTION DESCRIBES THE PROGRAM. FROM SO THE PATHWAYS TO PREVENTION WORKSHOPS IDENTIFY RESEARCH GAPS AND SELECTED SCIENTIFIC AREA, IDENTIFY METHODOLOGICAL AND SCIENTIFIC WEAKNESS IN THAT SCIENTIFIC AREA, SUGGEST RESEARCH NEEDS AND MOVE THE FIELD FORWARD THROUGH UNBIASED EVIDENCE BASED ASSESSMENT OF COMPLEX ISSUE. SOME WORDS I DRAW YOUR ATTENTION TO THERE IS UNBIASED THEY TAKE PAINS TO MAKE SURE THERE'S SEPARATION BETWEEN DIFFERENT STAGE OF PROJECT SO THERE'S NO INTRODUCTION OF BIAS ALONG THE WAY. SO THAT WE AS FEDERAL PARTNERS CAN'T PUT UNDUE INFLUENCE ON IT SO OUR ACADEMIC PARTNERS CAN'T PUT UNDUE INFLUENCE ON IT. THAT'S WHY WE HAVE SE CRY RECEIVE ALONG THE WAY. ARE DESIGNED FOR TOPICS THATHOPS- HAVE UNCOMPLETE OR UNDERDEVELOPED RESEARCH AND HAVE A NEED FOR SYNTHESIS AND CRITICAL ASSESSMENT OF THE PUBLISHED LITERATURE. WHAT THAT PART IS GETTING AT IS THE SYSTEMATIC EVIDENCE REVIEW, ONE OF THE OUTCOMES, SO SO THE WAY THIS WORKS IS OFFICE OF DISEASE PREVENTION ASKS FOR NOMINATES FROM TWO NIH ICs, FOR THIS PARTICULAR WORKSHOP NICHD AND NCMRR PARTNE WITH NINDS. AS WE HAVE OVERLAP IN THIS AREA OF PEOPLE WHO USE A WHEELCHAIR CHRONICALLY. EACH PATHWAY TO PREVENTION OR P 2P HAS TWO KEY OUTPUTS, A SYSTEMATIC EVIDENCE REVIEW PERFORM BY AGENCY FOR HEALTHCARE RESEARCH AND QUALITY OR AHRQ. THE SECOND IS THE ONE AND A HALF DAY WORKSHOP. AND THEY ARE DONE IN PARALLEL SO THEY ARE BASICALLY DONE AT THE SAME TIME. THERE WILL ALSO BE AT WORKSHOP THERE WILL BE AN INDEPENDENT PANEL APPOINTED BY OFFICE OF DISEASE PREVENTION AND THEY WILL TAKE THE SYSTEMATIC EVIDENCE REVIEW, AND THE WORKSHOP AND THEY WILL COMPILE A REPORT AT THE END WITH ACTION ITEMS FOR THE GOVERNMENT TO CONSIDER. SO THE P 2P FUNDS SYSTEMATIC AREAS OF UNDERDEVELOPED RESEARCH, HOW DO WE COME TO FOCUS ON THE PHYSICAL ACTIVITY FOR WHEELCHAIR USERS? ONE OF THE FIRST INSTIGATORS IN THIS WAS THE 2018 PHYSICAL ACTIVITY GUIDELINES. ALLISON WAS INVOLVED IN REVIEW OF THESE GUIDELINES AND WE KNEW THERE WOULD BE SOME POPULATIONS OF WHEELCHAIR USERS INCLUDED BUT RECOMMENDATIONS WOULD BE BASED ON RELATIVELY WEAK INFORMATION. SO THERE WASN'T STRONG SUPPORTING EVIDENCE FOR THAT. IN MANY CASES THESE PHYSICAL ACTIVITY GUIDELINES ARE BASED ON META ANALYSES OF OTHER STUDIES THROUGH SYSTEMATIC REVIEWS SO WE THOUGHT OKAY, WE CAN TAKE THIS PROGRAM HERE, AND WE CAN EITHER DO THE SYSTEMATIC REVIEW AND GENERATE THE EVIDENCE NEEDED FOR ADDITIONAL GUIDELINES OR WE CAN HIGHLIGHT THE NEEDS AND RESEARCH FIELD IF THE EVIDENCE DOESN'T EXIST. SO TO GIVE YOU AN IDEA OF THE RESULTS THAT WERE PUBLISH IN THE 2018 PHYSICAL ACTIVITY GUIDELINES, HERE IS AN EXCERPT FROM THE SECTION ON CHRONIC CONDITIONS. ON THE BOTTOM YOU CAN SEE MULTIPLE SCLEROSIS AND SPINAL CORD INJURY. WHERE IT SAYS IE, THAT MEANS INSUFFICIENT EVIDENCE TO DRAW ANY CONCLUSIONS THERE. YOU WILL SEE THE PHYSICAL FUNCTION COLUMN, THINGS LIKE IMPROVED WALKING, WHEELCHAIR SKILLS AND IMPROVED FITNESS. UNDER MULTIPLE SCLEROSIS WE HAVE IMPROVED COGNITION. OTHER AREAS THERE'S NOT ADDITIONAL REPORT FOR REDUCING DISEASE BURDEN OR THINGS LIKE THAT AND SECONDARY CONDITIONS THAT CAN ARISE FROM PROLONGED WHEELCHAIR USE. SO THAT IS HOW WE STARTED IN ON THIS TOPIC. ANOTHER PUBLICATION THAT CAME OUT AROUND THE SAME TIME IS NATIONAL ACADEMYIES REPORT ACADEMIES REPORT. WHICH IS THEY CONFIRM PREVIOUS RESEARCH THAT PREDICTS THE WHEELCHAIR USERS BETWEEN 2005 AND 2030 SO WE ARE IN THE MIDDLE OF THAT PERIOD RIGHT NOW AND I THINK WE NEED TO PREPARE FOR THIS EVENTUALALTY. SECOND IS THIS IDEA OF MATCHING THE RIGHT WHEELCHAIR, RIGHT ASSISTIVE TECHNOLOGY TO THE INDIVIDUAL. SO THAT CAN REALLY IMPROVE WORK FORCE PARTICIPATION COMMUNITY PARTICIPATION, AND ACTIVITY PARTICIPATION. SO WE WOULD LIKE TO BE ABLE TO MATCH EXERCISE REGIMEN OR ASIS ACTIVE TECHNOLOGY THAT IMPROVE COMMUNITY PARTICIPATION AS WELL. THAT'S SORT OF A FOCAL POINTS FOR NCMRR. OPINIONLY, THE REPORT REALLY HIGHLIGHT AD LACK OF DATA REGARDING WHEELCHAIR USE. SO WHEELCHAIR USE IS NOT ROUTINELY REPORTED IN THE LITERATURE. PARTICULARLY IN THE PHYSICAL ACTIVITY LITERATURE SO I WILL COME BACK TO THAT LATER. BUT THAT WAS KEY FOR US IN SHAPING AND SCOPING THIS PROJECT. THERE'S FEW AVAILABLE DATA SETS. ONE OF THE PROBABLY RICHEST DATA SETS THAT IS OUT THERE IS THIS CMS DATA WHICH YOU CAN LINK WHEELCHAIR USE OR PEOPLE HAVE BEEN PROVIDED WHEELCHAIR AND THEN LATER OUTCOMES. SO I STATED THIS TOPIC BUT LET'S HI ABOUT IT FOR A MINUTE. CAN PHYSICAL ACTIVITY IMPROVE THE HEALTH OF WHEELCHAIR USERS, IT'S A BROAD TOPIC. WE WILL NEED TO DEFINE PHYSICAL ACTIVITY AND HEALTH AND WHEELCHAIR USERS. BECAUSE IT INVOLVES A SYSTEMATIC EVIDENCE REVIEW WE ARE HEMMED IN BY WHAT IS AVAILABLE IN THE LITERATURE AND WHAT PUBLISHING CONVENTIONS ARE. IF RESEARCHERS AREN'T PUBLISHING DETAILS WE CAN'T REVIEW IN THE SYSTEMATIC EVIDENCE REVIEW. WE FIGURED QUICKLY THAT DOES NOT HAPPEN SO WHEN YOU HAVE POPULATION IN CLINICAL TRIALS CLINICAL TRIAL USING PHYSICAL ACTIVITY AS INTERVENTION YOU ARE NOT GOING TO SEE REPORTS OF WHETHER INDIVIDUALS ARE USING WHEELCHAIRS, HOW OFTEN THEY WERE USING WHEELCHAIRS, WHAT TYPE OF WHEELCHAIR THEY WERE USING. LET'S LOOK AT THE FOUR QUESTIONS SCOPING THIS INITIATIVE. SO FIRST IS WHAT ARE THE BENEFITS AND HARMS OF PHYSICAL ACTIVITY FOR INDIVIDUALS THAT USE A WHEELCHAIR. RELATIVELY STRAIGHT FORWARD WE WANT TO SEE WHAT THE BENEFITS ARE, BUT ALSO THE HARMS. SO ANY OUTCOMES THAT IMPROVE OR GET WORSE OVER TIME. TOGETHER WITH HOUR OUR COLLEAGUES HAT NINDS AND PARTNERS AT ODP ANDS AHRQ, WE REALLY REFINED THIS LIST OF OUTCOMES BOTH TO MEET THE NEEDS OF THE POPULATION BUT ALSO WHAT WAS FEASIBLE FOR AHRQ TO REVIEW. SO THE SECOND IS WHICH FACTORS OF THE ACTIVITY DRIVE BENEFITS AND HARMS? SO THAT'S BASICALLY THE TYPE OF ACTIVITY THE AMOUNT OF ACTIVITY, SO WE ALSO HAD TO CONSIDER WHAT WE WOULD INCLUDE THERE. ARE WE GOING TO INCLUDE -- I'LL SAY WE DID INCLUDE THINGS LIKE WEIGHTLIFTING AND RESISTANCE BANDS, OBVIOUSLY AEROBIC EXERCISE, THINGS LIKE THAT, WE ALSO INCLUDED NIH THERAPY, HORSE BACK RIDING WHICH IS VERY COMMONLY USED IN CEREBRAL PALSY RESEARCH. THE THIRD QUESTION IS WHICH HUMAN FACTORS DRIVE BENEFITS AND HARMS. WHAT'S THE PRIMARY CAUSE OF WHEELCHAIR USE. WHAT'S THE AGE OF THE INDIVIDUAL OR POPULATION GENDER RACE ETHNICITY, ALL THOSE SORTS OF THINGS TO SEE IF WE CAN TEASE OUT ANY HUMAN FACTORS DRIVING CHANGES IN OUTCOMES. THE FOURTH QUESTION WHAT ARE THE ANALOGY WEAKNESSES, WE KNOW THERE ARE A NUMBER OUT THERE, SO LET'S IDENTIFY THEM AND SEE HOW WE CAN APPROACH THEM. ONE OF THE THINGS WE QUICKLY FOUND OUT WORKING WITH THE EVIDENCE BASED PRACTICE CENTER AND AHRQ, IS THAT BECAUSE WHEELCHAIR USE IS NOT REPORTED, IN THE LITERATURE WE HAVE TO DEFINE WHEELCHAIR USE IN A DIFFERENT WAY. SO WE ACTUALLY IDENTIFIED OUR POPULATION AS BEING INDIVIDUALS WHO HAD SPINAL CORD INJURY OR MULTIPLE SCLEROSIS OR CEREBRAL PALSY, WE FELT THIS GAVE US A GOOD SAMPLE OF THE POPULATION OF WHEELCHAIR USERS WITH PEDIATRIC ONSET ADULT ONSET DEGENERATIVE RELATIVELY STABLE CONDITIONS. SO TRY TO CAPTURE THE WHOLE FIELD. SO AT THIS POINT EEL START DISCUSSING SOME OF THE LARGER STRUCTURE OF THE PATHWAYS TO PREVENTION PROGRAM. FIRST LET ME DO THESE GOALS. SO THE GOALS ARE TO INFORM THE FUTURE CLINICAL PRACTICE GUIDELINES SO MAINLY PHYSICAL ACTIVITY GUIDELINES BUT OTHER GUIDELINES. IDENTIFY GAPS, INFORM FUTURE RESEARCH AND CREATE A PLAN WITH OUR FEDERAL PARTNERS. THAT IS THE IMPLEMENTATION PLAN THAT WILL COME AT THE END OF THIS. SO THI IMAGE FROM THE ODP WEBSITE OFFICE OF DISEASE PREVENTION WEBSITE, SHOW IT IS PROCESS FOR PATHWAYS TO PREVENTION EFFORT, IT'S COMPLICATED AND TAKES THREE YEARS OF EFFORT. WITH NUMEROUS OFFICES AND AGENCIES BUT WE'LL WALK THROUGH IT. FROM FIRST AS I SAID TWO ICs AND PARTNERS -- JUDGED BY ODP STAFF ON RELEVANCE TO PREVENTION AND POTENTIAL IMPACT OF WORK SO THEY ARE EXCITED ABOUT THIS PROJECT. WE WORKED WITH NINDS AND ODP TO REFINE THE ISSUE BUT IT WAS ALWAYS AN ISSUE MAKING SURE OUR EYES WERE NOT BIGGER THAN OUR STOMACH AND WE COULD FEEDSBLY DO THIS. SO THE SECOND SECTION HERE SHOWS THAT AFTER THE PROPOSALS ACCEPTED IT SPLITS INTO TWO STREAMS. ON THE TOP UP HERE YOU SEE THIS ORANGE LINE, THAT'S A SYSTEMATIC EVIDENCE REVIEW. SO THAT OCCURS THROUGH THE AHRQ EVIDENCE BASED PRACTICE CENTERS AND THOSE ARE SET OF 12 CONTRACTED CENTERS THAT MAINLY ACADEMIC THOUGH SOME IN PRIVATE SECTOR, THAT PERFORM THESE EVIDENCE BASED SYSTEMATIC EVIDENCE REVIEWS. SO THE NAME OF THIS WILL SPECIFIC CENTER CONDUCTING THIS IS CONFIDENTIAL AND WON'T BE REVEALED UNTIL WORKSHOP OR UNTIL THEY POST THE DRAFT REPORT A FEW WEEKS BEFORE THE WORKSHOP. IS THEY ARE USING A P COX FRAMEWORK DEVELOPED WITH ODP NCMRR AND NINDS. AND IT'S CURRENTLY UNDERGOING PEER REVIEW SO WE HAVE SEEN THE DRAFT OF THIS REPORT NOW AND THOUGH WE CAN'T SHARE THE DETAILS I THINK WE ARE HAPPY WITH IT. THE EVIDENCE REVIEW AND WORKSHOP REALLY ARE BOTH CENTERED AROUND FOUR KEY QUESTIONS, I WENT OVER THEM IN ROUGH DRAFT BEFORE. LIMITED TO THE THREE CONDITIONS SPINAL CORD CEREBRAL PALSY, WE HAD TO DEFINE PHYSICAL ACTIVITY SO WE DEFINES AS A GROSS MOTOR ACTIVITY THAT INCREASES ENERGY EXPENDITURE. SO A REASONABLE JUST WE WANTED TO HAVE A REASONABLE PERSON THINK THEY INCREASE ENERGY EXPENDITURE. WE DID GROSS MOTHER ACTIVITY BECAUSE WE DIDN'T -- MOTOR ACTIVITY BECAUSE WE DIDN'T WANT TO INCLUDE STUDIES FOCUSED ON ONE JOINT OR LIKE THE HAND THAT WOULD BE HAVE A WIDE IMPACT ON THE BODY. WE NEEDED TO INCLUDE ADDITIONAL LIMITERS ON THAT SUCH AS DOSE AND FREQUENCY SO WE COULD AGAIN KEEP IT IN SCOPE AND KEEP IT MANAGEABLE. -- MANAGEABLE. SO THIS OTHER TRACK IN THIS LOWER TRACT DOWN HERE, IS THE WORKSHOP PLANNING. IT BEGAN WITH A MEETING OF FEDERAL GOVERNMENT STAKEHOLDERS FROM NIH DBA AND I LOOKED AT SOME AGENCIES THERE, CDC, FDA, NIDLER ALSO REPRESENT SOD IT WAS GREAT MEETING -- SO IT WAS A GREAT MEETING WE PUT TOGETHER AND NOMINATED SOME EXPERTS FROM ACADEMIA, AND ALSO OTHER STAKEHOLDERS SO CAREGIVERS AND PRACTITIONERS AND ADVOCATES TO COME TO IN CONTENT AREA EXPERT MEETING TO NOMINATE SPEAKERS. THEN WE HELD THAT MEETING TO AGAIN GO OVER THE AGENDA, TO SHAPE IT AND TO NOMINATE THE SPEAKERS. THAT WAS ALSO VERY PRODUCTIVE, VERY ENGAGING, AND I THINK WE GOT A LOT OUT OF IT. AT THE SAME TIME THE OFFICE OF DISEASE PREVENTION NOMINATES THEY WERE PANEL. SO IT'S A -- AGAIN, THIS IS THE PANEL MEMBERS ARE SECRET. ACCEPT FOR THE CHAIR. THE IDEA THERE IS TO KEEP IT UNBIASED SO OUTCOMES ARE NOT INFLUENCED BY ANYONE FROM OUTSIDE THAT PANEL. I CAN TELL YOU THAT THE CHAIR OF THE MEETING WILL BE THOMAS LEVIST DEAN AND PROFESSOR WEATHER HEAD PRESIDENTIAL CHAIR AND HEALTH EQUITY TULANE UNIVERSITY. SO AGAIN THIS IS THE DETAILS WHERE THE MEETING WILL BE HELD M. LET ME JUST GO INTO THE AGENDA BRIEFLY. THIS IS THE INTRODUCTORY SESSION SO DR. BIANCI OPENED THE MEETING AND THEN THE DIRECTOR FOR PREVENTION RESEARCH, DAVID AND MURRAY WILL GIVE A CHARGE TO THE WORKSHOP PANEL. ALLISON IS GOING TO GIVE AN OVERVIEW OF THE WORKSHOP AND SCOPE THE PROBLEM FOR THE COMMUNITY. THEN WE'LL HAVE AN INTRODUCTION FROM THE CHAIR, THOMAS AND OUR KEYNOTE SPEAKER IS GOING TO BE CARRIE MORGAN FROM WASHINGTON UNIVERSITY ST. LOUIS. SHE WAS ALSO ON OUR CONTENT AREA EXPERTS PANEL AND WAS NOMINATED FOR THIS ROLE BY UNANIMOUS ACCLAIM BY THAT MEETING. SO IT WAS PRETTY EXCITING TO HAVE HER. KEY QUESTION ONE, WHAT IS THE EVIDENCE BASE PHYSICAL ACTIVITY INTERVENTIONS TO PREVENT OBESITY DIABETES AND CARDIOVASCULAR CONDITIONS INCLUDING EVIDENCE FOR HARMS OF INTERVENTIONS IN PEOPLE WITH MULTIPLE SCLEROSIS, CEREBRAL PALSY OR SPINAL CORD INJURY AT RISK OR CURRENTLY USING A WHEEL ABILITY DEVICE. THE TERMINOLOGY IS DIFFERENT BECAUSE WE HAD TO SHAPE IT TO FIT THE NEEDS OF THE SYSTEMATIC REVIEW. SO SINCE WHEELCHAIR USE IS NOT REPORTED, WE SAID THEY'RE AT RISK FOR USING A WHEELCHAIR SINCE THEY HAVE THESE CONDITIONS. THEN WE DID INCLUDE SCOOTERS MOTOR ORIZED WHEELCHAIRS IN THIS DEFINITION. SO FIRST WILL BE A SUMMARY OF THE FINDINGS OF KEY QUESTION ONE FROM EVIDENCE BASED PRACTICE CENTER. THEN WE WILL BE FOLLOWED UP BY PRESENTATIONS FROM JIM REMMER AND ROB WHO WILL GO INTO WHAT'S DONE RIGHT NOW IN THE FIELD, WHAT'S THE CUTTING EDGE RESEARCH IN THE FIELD? THERE WILL BE 40 MINUTES FOR DISCUSSION AFTER THIS, SO IT'S REALLY MEANT TO BE AN INTERACTIVE MEETING. THE SECOND KEY QUESTION, WHAT ARE BENEFITS AND HARMS OF PHYSICAL ACTIVITY INTERVENTIONS FOR PEOPLE AT RISK CURRENTLY USING WHEEL MOBILITY DEVICE. FOR THIS, AGAIN, THERE WILL BE A PRESENTATION FROM THE EVIDENCE BASED PRACTICE CENTER SUMMARIZING THOSE RESULTS. THEN WE HAVE A PANELIST WILL BE OUR SPEAKERS WILL BE DIANE FROM THE NIH CLINICAL CENTER HERE, SHERRI BLOETTE, JEFF AND KAREN CORD, KAREN IS PRACTITIONER AND SHE'S GOING TO GIVE THE PRACTITIONER PERSPECTIVE OF WHAT IT'S LIKE TO GET PEOPLE INVOLVED IN PHYSICAL ACTIVITY AND TO KEEP THEM INVOLVED IN PHYSICAL ACTIVITY. QUESTION THREE, WHAT ARE THE PATIENT FACTORS THAT MAY EFFECT BENEFITS AND HARMS OF PHYSICAL ACTIVITY IN PATIENTS ATTRIST RISK FOR OR CURRENTLY USING A MOBILITY DEVICE. WE HAVE A SUMMARY OF THE EVIDENCE FROM THE EVIDENCE BASED PRACTICE CENTER. AND PRESENTATIONS FROM ED HERVITS, MARSHA AND BRETT SMITH. WE'LL HAVE COMMUNITY REPRESENTATIVE ANGELA WHITE WHO SHE RUN AS MULTIPLE SCLEROSIS SUPPORT GROUP CALLED THE MIGHTY SPIRIT. WITH THIS PANEL IS GOING TO FOCUS ON IS THE BARRIERS THAT PEOPLE ENCOUNTER WHEN TRYING TO ENGAGE IN PHYSICAL ACTIVITY. AND BOTH SOME OF THE PHYSICAL WE THINK ABOUT AND EMOTIONAL AND PSYCHOLOGICAL BARRIERS THAT MAKE IT DIFFICULT FOR PEOPLE TO PARTICIPATE IN PHYSICAL ACTIVITY. A FINAL KEY QUESTION, WHAT ARE THE METHODOLOGICAL WEAKNESSES AND GAPS TO RETURN BENEFITS AND HARMS OF PATIENTS AT RISK FOR OR CURRENTLY USING A MOBILITY DEVICE. THIS SESSION WILL HAVE AUDREY HIX, KATHERINE ROBY, DAN AND MARCUS AND THIS SESSION WILL FOCUS MORE ON THE METHODOLOGICAL NEEDS IN THE FIELD AND SO HOW DO WE MEASURE OUTCOMES HOW DO WE STRUCTURE TRIALS, HOW DO WE REPORT ADVERSE EVENTS, THINGS LIKE THAT, THIS WILL BE A GREAT PANEL TO HIGHLIGHT WHAT WE NEED TO DO MOVING FORWARD. OUR FINAL PANEL SESSION FIVE HERE, IS SORT OF ALL INDIVIDUALS PRESENTED WITH COMMUNITY PERSPECTIVE FROM SOME POSITION OR ANOTHER. SO STEVEN IS A GENTLEMAN WHO HAS CEREBRAL PALSY, HE RUNS A FOUNDATION AND HE HAS A CAMP FOR KIDS WITH CEREBRAL PALSY TO GO PARTICIPATE AND IN CAMP ACTIVITIES TO GO SWIMMING AND FISHING AND CANOEING AN THOSE THINGS. JUST SEEMS TO HAVE GREAT IMPACT ON THE KIDS, HE'S ALSO KNOWN FOR HAVING SCALED EL CAPTAIN USING A SPECIALIZED RIG THAT HE BUILT. MICHELLE IS THE CEO OF CEREBRAL PALSY MOW. SHE IS A PARENT CAREGIVER ADVOCATE, A DAUGHTER WITH CEREBRAL PALSY. RACHEL COWAN IS RESEARCHER AT UNIVERSITY OF ALABAMA BIRMINGHAM, SHE HERSELF USES A WHEELCHAIR. AND THE DISCUSSION WILL BE MODERATED BY THE MS SOCIETY. OUR CLOSING SESSION WILL BE LYNN JAKEMAN, NOW DIRECTOR OF DIVISION OF NEUROSCIENCE AT NINDS. SO THAT BRINGS US TO THIS LAST LINE PAST THE WORKSHOP AND WHAT'S DISSEMINATION PLAN, THE FOLLOW-UP AND DELIVERABLES. SO THE SYSTEMATIC EVIDENCE REVIEW POSTED IN DRAFT COMMENT IN EARLY 2020, THE EVIDENCE BASED PRACTICE CENTER WILL TAKE THOSE COMMENTS INTO ACCOUNT AND PUBLISH A FINAL VERSION IN 2020. THE WORKSHOP ITSELF WILL BE MARCH 30 AND 31st, 2020, THE PANEL REPORT WE EXPECT TO BE OUT IN THE SPRING OR EARLY SUMMER SHORTLY AFTER THAT MEETING. WITH THAT IN HAND WE WILL PLAN A FEDERAL PARTNERS MEETING GOING BACK TO THE BEGINNING WHERE WE HAD OUR FEDERAL PARTNERS SELECTING THE EXPERTS AND GO BACK AND SEE OKAY, WHAT ARE OUR ACTION ITEMS, FROM THE GOVERNMENT PERSPECTIVE. AGAIN I'LL LEAVE THIS UP IF ANYONE NEEDS MORE INFORMATION OR TIME TO SEE HOW TO REGISTER OR TO FIND A VIDEOCAST. I WILL TAKE ANY QUESTIONS. [APPLAUSE] >> WITH REGARD TO YOUR THREE PATIENT GROUPS, ARE YOU ALSO GOING TO INCLUDE CONGENITAL SPINAL CORD INJURY ESSENTIALLY SPINAL DISRAPPISM OR SPINA BIFIDA WITH SPINAL CORD INJURY? ARE YOU EXCLUDING SPINA BIFIDA? >> WE DID NOT EXCLUDE IT. BUT I CAN'T THINK OF ANY STUDIES THAT WERE INCLUDED. I'M LOOKING AT ALLISON, SHE'S ALSO NODDING. THAT MAY BE -- (OFF MIC) >> I DON'T THINK WE EXCLUDED THEM, I DON'T KNOW IF THERE WERE ANY THAT MET THE CRITERIA TO BE INCLUDED IN THE REVIEW. >> WHAT I AM THINKING IS IT'S ALSO POSSIBLE THEY WEREN'T EXCLUDED FROM THE TRIALS SO IF THE TRIAL WAS ACCEPTING TO ALL CAUSE SPINAL INJURY IN ADULTS, THAT MIGHT NOT REALLY REPORTED IT SO THAT OUR GUIDELINES INCLUSION CRITERIA DID HAVE WIGGLE ROOM ALSO THAT ALL PATIENTS DID NOT HAVE TO HAVE I THINK OVER 50%, OVER 80% WE CHANGED A FEW TIMES BUT THERE COULD BE ADDITIONAL POPULATIONS IN THE STUDIES IS WHAT I'M GETTING AT. I DON'T KNOW SPECIFICALLY IF ANY (INAUDIBLE). ALSO I SHOULD SAY THE WORKSHOP ITSELF CAN COVER ANY POPULATION OF WHEELCHAIR USERS SO THEY ARE ENCOURAGE TO BRING IN ADDITIONAL DATA. BUT FOR THE PURPOSE OF SCOPING THE EVIDENCE REVIEW WE REALLY HAD TO NARROW IT DOWN. >> THERE HAS BEEN QUITE A BIT OF WORK WITH REGARD TO METABOLIC SYNDROME AND SPINA BIFIDA, OBESITY AND SOME EXERCISE INTERVENTIONS IN THAT POP PLACE. SO IT'S GREAT THAT YOU ARE INCLUDING IN THE WORKSHOP POTENTIALLY. >> THANKS FOR THAT NICE OVERVIEW. DO YOU KNOW HOW MANY P 2 P PROJECTS ARE ACTIVE AT ANY GIVEN TIME FROM THE EARLIEST PLANNING STAGES THROUGH THE CONFERENCE? DO WE HAVE OTHER TOPICS THAT WE ARE BEGINNING TO PURSUE IN NCMRR? >> THERE'S NO TOPICS CURRENTLY UNDER CONSIDERATION AT NCMHRR. THEY TYPICALLY HAVE TWO PUBLICLY ANNOUNCED, MAYBE TWO MORE NOT YET PUBLICLY ANNOUNCED. RIGHT NOW WE ARE THE ONLY ONE THAT HAS BEEN ANNOUNCED. IF YOU GO TO THEIR WEBSITE WILL BE THE ONLY ONE ON THERE. AND I THIS I THAT'S JUST A SORT OF NATURAL LULL EBB AND FLOW HOW THINGS GO. BUT THEY TRY TO DO TWO A YEAR. ESSENTIALLY. AND SO IT'S A COMPETITIVE PROCESS TO GET SELECTED, I DON'T KNOW THEY WOULD LET US DO TWO IN A ROW, HAVE TO SPREAD THE MONEY A LITTLE BIT. I FORGOT TO MENTION THAT ALL THIS IS PAID FOR THROUGH OFFICE OF DIRECTOR AT NIH SO NCMRR DOESN'T USE FUNDS ON THIS. SO IT'S REALLY NICE TO HAVE THE SUPPORT OF THE BROADER NIH COMMUNITY. QUESTION? >> I WANTED TO THANK JOE FOR THE WORK ON THIS. IT STARTED WHEN HE WAS A, AAAS FELLOW AND THIS WAS A PROJECT THREE YEARS AGO. HE'S BEEN ABLE TO STAY WITH IT AND FOLLOW THROUGH. HE'S TAKEN THE LEAD, WE ARE THANKFUL FOR THAT. >> ANY MORE QUESTIONS? THANK YOU. >> THANK YOU VERY MUCH. [APPLAUSE] O ALL RIGHT. NEXT WE'LL HEAR FROM TWO OF OUR OWN. JENNIFER STEVENS LAPSLEY AND ROD WUDLICK ARE GOING TO TEAM UP TO PRESENT TEAMING WITH PARTICIPANTS TO IMPROVE THE VALIDITY AND RIGOR OF REHABILITATION RESEARCH. I KNOW THAT BOTH JENNIFER AND ROB PUT A GREAT DEAL OF TIME AND THOUGHT AND EFFORT INTO THIS AND WE APPRECIATE THEM TAKING THE TIME TO INFORM US. >> I'M ROB WUDLICK, I'M ON THE ADVISORY COUNCIL AS ALL OF YOU HERE KNOW. EIGHT YEARS AGO I HAD A SPINAL CORD INJURY AND GOT REALLY MOTIVATED TO GET BETTER DO WHATEVER I CAN. THAT'S WHAT BROUGHT ME HERE. AND BROUGHT ME ALONG THIS CAREER PATHWAY. I'M PROBABLY A MODEL PERSON TO BE A ENGAGED PARTICIPANT IN RESEARCH. WITH LIVING WITH THE DISEASE CONDITION. I RECENTLY JUST GOT PROJECT MANAGER AT UNIVERSITY OF MINNESOTA REHABILITATION MEDICINE DEPARTMENT. GOING ON ADAPTIVE TECH ASSISTIVE DEVICE COMPANY THAT MAKE THESE PHONE HOLDERS AND PRETTY SIMPLE THINGS AND TRY TO FIT UNMET NEEDS WITH THAT. FOR THE PAST THREE YEARS THEY HAVE BEEN DEVELOPING UPPER EXTREMITY EXOSKELETON FOR NEUROMUSCULAR CONDITIONS, SHOULDER, ELBOW. SO IT'S REALLY INTERESTING HAVING A PATIENT PERSPECTIVE AND (INAUDIBLE) DONE RESEARCH GRANT CONSULTING AND IT WAS ONE CO-FOUNDER APRILSIS AND WAS CHAIR FOR -- PARALYSIS, WAS CHAIR FOR THE FIRST FOUR YEARS AND STEPPED DOWN TO RUN THE BOOKS. >> FANTASTIC, IT'S BEEN FUN TO WORK WITH ROB PUTTING THIS TOGETHER BECAUSE WHILE I GREATLY VALUED STAKEHOLDER ENGAGEMENT THIS HAS GIVEN ME MORE IN DEPTH LOOK. AS TO THE IMPORTANCE OF TEAMING WITH PARTICIPANTS SO I'M A PROFESSOR AT THE UNIVERSITY OF COLORADO AND HEALTH SCIENTIST AT THE VA EASTERN COLORADO HEALTH SYSTEM, MINE IS FOCUSED ON OLDER POPULATIONS AND ENHANCING MOBILITY AND IMPROVING PHYSICAL FUNCTION THROUGH MORE PROGRESSIVE MANY TIMES TECHNOLOGY ENABLED SOLUTIONS. WE WORKED IN RESEARCH FOCUSED ON MECHANISMS ALL THE WAY UP MORE RECENTLY TO IMPLEMENTATION SCIENCE PRAGMATIC TRIALS, SO QUITE A RANGE. I THINK THAT WILL BE REFLECTED HERE ADS WE GO THROUGH THIS PRESENTATION. >> JUST TO GET STARTED WE WANTED TO ADD A LITTLE BIT PERSONAL PERSPECTIVE. THIS IS ME TESTING DEVICE SO I WEAR A LOT OF HATS THERE FROM SIMPLY TESTING AND BEING THE GUINEA PIG TO ORDERING SUPPLIES AN HELPING DESIGN THINGS, MAKE PROTOTYPES. PRETTY COOL EXPERIENCE BEING ABLE TO BE ON THE OTHER SIDE OF GRANTS, WE GOT SBIR GRANT OUT OF NCMRR A FEW YEARS AGO. THAT WAS A REALLY FUN PROJECT. >> I HAVE A COUPLE OF REALLY WE ARE TALKING ABOUT HOW PATIENTS REALLY SHAPE THE WORK THAT WE ARE DOING AND THEY ROUND THE VALUE OF WHAT WE ARE DOING. SOMETIMES GET FOCUSED ON RESEARCH ASPECTS OF SPECIFIC OF SOME ASPECTS OF WHAT YOU ARE STUDYING. REMEMBERING WHY YOU ARE DOING WHAT YOU ARE DOING IN TERMS OF ENGAGING STAKEHOLDERS IS THE FOCUS OF THIS PRESENTATION. THIS IS A PICTURE OF ONE OF MY EARLY PATIENTS AND ONE OF OUR CLINICAL TRIALS WHO WENT ON TO BECOME CONSULTANT AND HELP US WITH FUTURE CLINICAL TRIALS AND INTERVENTION STRATEGIES AS WELL AS ONE OF MY FAVORITE PATIENTS, MANY, MANY YEARS AGO IF YOU SEE THE RESEMBLANCE IN TERMS OF THIS INDIVIDUAL HE PROMISED A 6-YEAR-OLD IN THE WAITING ROOM HE WAS GOING TO RECOVER FROM THE BILATERAL KNEE REPLACEMENTS IN TIME TO DELIVER CHRISTMAS PRESENTS IN DECEMBER. SO WE GOT HIM BACK TO FISCAL LEVEL OF FUNCTION SO MEMORIES AN JOYS OF WORKING WITH THESE INDIVIDUALS THAT DRIVE THE WORK WE ARE DOING. AGAIN, WELL ROUNDED APPROACH OF INCLUDING THEM IN ALLS IS ASPECTS OF WHAT WE ARE DOING. I LOVE THIS PICTURE, BECAUSE THIS TO ME REPRESENT IT IS CLASSIC ACADEMIC COMING INTO A CLINICAL ARENA AND SAYING I'M GOING TO BRING IN THIS IDEA AND RESEARCH STUDY AND I'M GOING TO SOLVE YOUR PROBLEMS. I WILL PUT YOUR FIRES OUT. IN FACT CLINICIANS ARE GOING WAIT A SECOND THAT'S NOT THE FIRE OF CONCERN. THAT'S FAR FROM OUR -- NOT EVEN ON THE LIST OF CONCERNS. HERE ARE THE ISSUES WE ARE DEALING WITH ON A DAILY BASIS. HERE ARE THE CONCERNS THAT WE NEED TO ADDRESS, SO A NICE ILLUSTRATION OF FIREFIGHTERS POINTING POINTING THE HOSE IN THE WRONG DIRECTION. IF ER NOT COMBINING EFFORTS IN ACADEMICS WITH CLINICAL ARENAS IN WAYS WE ARE INTERFACING ON A DAILY BASIS AND BECOMING PART OF THE TEAM, AND ENGAGING STAKEHOLDERS WE WILL BE POINTING OUR HOSE IN THE WRONG DIRECTION AS WE ANSWER QUESTIONS. >> A LOT OF THIS TALK IS ABOUT PATIENT ENGAGEMENT. IT ALL IS BUT WHY. AND SO WE LOOKED AT STUDIES BEFORE THIS TALK AND PCORI OBVIOUSLY HAS DONE RESEARCH INTO THIS. AND PATIENT ENGAGEMENT IS NOT NEW BUT IT'S BECOMING MORE A FOCUS INITIATIVE I THINK FOR A LOT OF DIFFERENT FROM A LOT OF DIFFERENT PERSPECTIVES, IT BASICALLY HELPS DELIVER BETTER OUTCOMES FROM WHAT WE HAVE SEEN. AND EXPERIENCED IT EVERY DAY I'M IN THE ROOM CONTRIBUTING TO THE DEVELOPMENT OF PROJECT THROUGH WHAT NOT. I HAVE GOT A LOT OF PERSPECTIVE TOO. MAYBE WERE NOT HAVE BEEN THERE. ONE THING WE MENTION IS PARTICIPANTS AREN'T JUST PATIENTS IN THIS PARTICULAR SCENARIO, THEY ARE PAYERS, PROVIDERS THEY CAN BE POLICY MAKERS. THEY ARE ALL THE PEOPLE AT THE TABLE IN TERMS OF MAKING AND INFLUENCING CLINICAL CARE. THIS ROOM IS WELL FAMILIAR WITH THIS STATISTIC, IT TAKES 17 YEARS TO TRANSLATE 14% ORIGINAL RESEARCH INTO CLINICAL PRACTICE. NOW WHEN WHEN YOU ADD THE TIME TO CONDUCT THE STUDY ITSELF, THE TIME TO GET THE GRANT FUNDED AN COLLECT THE PILOT DATA WE BACK OURSELVES UP TO 25 YEARS. SO ONE OF THE QUESTIONS IS WHY IS THIS -- WHY DOES IT TAKE SO LONG. AND WHAT WE ARE POSING TO THE GROUP IS ONE POTENTIAL SOLUTION IS IF WE CAN ACTUALLY DESIGN INTERVENTIONS AND STUDIES WITH STAKEHOLDERS FROM THE GET GO MAYBE THE TRANSLATION WILL BE MORE FEASIBLE. SO A LOT OF TIMES IF WE ARE DESIGNING SOMETHING IN ISOLATION THAT NEXT STEP THAT TRANSLATION PLAYING THAT GAME OF CHESS AND LOOKING TWO OR THREE STEPS DOWN THE ROAD IN TERMS OF UPTAKE AND ACTUAL IMPLEMENTATION HASN'T BEEN WELL THOUGHT OUT. REALLY ENGAGING PEOPLE AT THE TIME FROM THE BEGINNING TO SHORTEN THIS TIME FRAME FROM 25 OR 17 YEARS DOWN TO MORE PALATABLE TIME FRAME. >> SOMEBODY WITHOUT FULLY DEPENDENT ON CAREGIVERS, MY MOM, MY PARENTS AND FAMILY, 17 YEARS IS WAY TOO LONG. 14%, THERE'S A LOT OF INEFFICIENCY IN THAT. YOU MAY BE LOOKING TO THE RIGHT AREA, ARE YOU ASKING THE RIGHT QUESTIONS. WHAT'S DELAYING THAT. >> SO WHAT'S THE CURRENT STATE? WE HAVE A LOT OF EXAMPLES OF SCENARIOS THAT I THINK ARE GRADUALLY CHANGING OVER TIME BUT WHEN WE LOOK AT THE PHARMACEUTICAL INDUSTRY AND SEE DRUGS LIKE AM BEE YEN PUT OR NOT MARKET AT HIGHER DOSE THAN CURRENTLY RECOMMENDED NOW FOR WOMEN, WHETHER OR NOT ALL THESE DRUGS ARE TEST IN A CROSS SECTION OF INDIVIDUALS THAT RUELY REPRESENTS THE POPULATIONS THAT ARE USING THESE DRUGS, HAS BEEN SUBJECT OF DEBATE AND CONCERN IN MANY CASES. SO WITH AMBEIEN THE DOSE HAS TO BE REDUCED WHEN SIDE EFFECTS WERE MORE SUBSTANTIAL. THERE'S EXAMPLES OF BIOMECHANICAL MODELS WHETHER ROBOTS O MUSCLE MODELING, WHETHER TRADITIONAL GATE LAB TYPES OF APPROACHES WHERE WE REALLY BASE THOSE MODELS ON A PROTOTYPE, A SIX FOOT MALE WEIGHS 180 POUNDS AND WE FORM ALL OUR EXPECTATIONS AND CALCULATIONS AROUND THOSE PARTICULAR PROTOTYPES SO NASA DOES THE SAME THING OR HAS CERTAINLY DONE IN THE PAST IN TERMS OF HAVING CERTAIN PARAMETERS AND GUIDELINES. WHEN I COMES TO SOMEONE FOUR FOOT EIGHT COMPARING THAT TO SOMEONE BASING MODELS AND PROJECTIONS ON SOMEONE SIX FOOT IS GOING TO RESULT IN VERY DIFFERENT OUTCOMES. SO TAKING INTO ACCOUNT THINGS LIKE RACE AND CULTURE AND DISABILITY AND VETERAN STATUS ARE REALLY IMPORTANT FOR UNDERSTANDING THE SUBPOPULATIONS, SO IF A PATIENT POPULATION IS AT RISK FOR A PARTICULAR CONDITION WE HAVE INCLUDED AND REPRESENTED THEM ADEQUATELY IN OUR RESEARCH SO WE CAN IDENTIFY MAYBE PREMIUMTIVE MEASURES OR SCREENING OR ALTERNATIVE FOR EXAMPLE SUBPOPULATION AT RISK FOR CARDIOVASCULAR DISEASE WE OBVIOUSLY CAN IMPLEMENT MORE SCREENING STRATEGIES TO PREVENT SOME OF THE SEQUELLAE THAT MIGHT ENSUE OTHERWISE. >> WHERE CAN YOU ENGAGE PATIENTS IN YOUR RESEARCH? AND THE ANSWER IS EVERYWHERE. MY FRIENDS AT PRACTICE FORMER -- INSTITUTE CREATED A CHART AND HAND OUTS BUT I FORGOT THEM BACK IN MINNESOTA. SO MAYBE YOU'LL SEE THEM IN THE SPRING. YEAH, THIS WE ALL ARE GOING TO BE GOING OUT FOR THE REST OF THE PRESENTATION. BUT THIS IS JUST THE BASIC OVERVIEW OF EVERYTHING FROM THE DEVELOPING RESEARCH QUESTION MAYBE FIELD OF RESEARCH YOU WANT TO GO INTO ALL THE WAY, EVERY STEP OF THE WAY THEY CAN BE INVOLVED. ALTHOUGH DISSEMINATE AGO AND PUBLISHING YOUR PAPER. >> WE HAVE A CHEST BOARD THERE BECAUSE I THINK ABOUT THE GAME IN TERMS OF THE SCIENCE IF YOU CA TRULY THINK TWO OR THREE STEPS DOWN THE ROAD AS MENTIONED EARLIER AND ANTICIPATE THE INVOLVEMENT AS ONE OF THOSE PIECES YOU WILL END UP WITH A MUCH BETTER PRODUCT. >> TO FOCUS ON WHEN YOU ARE DEVELOPING STUDY DESIGN, WHAT KIND OF OUTCOMES ARE YOU LOOKING FOR? THAT CAN MEAN A LOT. THERE'S A LOT OF SCORES AND METRICS THAT REALLY DON'T MEAN A LOT TO A USER. THEY MIGHT MEAN A LOT TO ONE POPULATION BUT MAYBE NOT TO A DIFFERENT. SO THAT'S REALLY IMPORTANT TO GET KIND OF THAT FEEDBACK WHEN TRYING TO DEVELOP OUTCOME MEASURES, YOUR METHODOLOGY WHEN YOU ARE WRITING A GRANT. SO ON. AND CONDUCTING RESEARCH. I THINK THERE'S A LOT OF IF YOU FIND THE RIGHT ADVOCATES TO WORK WITH YOU, THEY CAN HELP WITH RECRUITMENT THEY CAN HELP WITH DEVELOPING PROTOCOLS BETTER, PILOT TESTING SO ON A LOT WITH THE INTERPRETATION DISSEMINATION DELIVERING SOMETHING MEANINGFUL. OBVIOUSLY THERE'S A LOT OF BENEFITS GENERATION VALIDATION OF YOUR CONCEPTS, CREATING MORE COMPETITIVE VIEWPOINTS. THAT'S DEFINITELY ADDING CONSUMER PERSPECTIVE. I HOPE MEAN A LOT OF MADE A HUGE DIFFERENCE IN REVIEW ROOM TRYING TO FIND GOOD REPRESENTATIVES FOR YOUR PROJECTS. SOMETIMES YOU NEED TO FIND MORE THAN ONE. I'M A PARAPLEGIC. MY NEEDS ARE DIFFERENT THAN SOMEBODY WHO IS PARAPLEGIC WITH SPINAL CORD INJURY. SO IMPROVING UNDERSTANDING THE PEOPLE YOU ARE WORKING TO TRY TO HELP AND THERE'S SKILLS OUTSIDE OF OUR CONDITIONS. I HAVE A DISEASE CONDITION BUT I'M ALSO AN ENNEAR. THERE'S DOCTORS OUT THERE THAT HAVE SUFFERED INJURIES OR GOING THROUGH HEALTH ISSUES SO ON S. THIS IS JUST SOMETHING GOING ON RIGHT NOW, AND I THOUGHT IT WAS FAIRY RELEVANT. THE FDA JUST FINISHED AN RFI TO TRY TO GET DEVICE MAKERS TO GET MORE CONSUMER INPUT IN THEIR MEDICAL DEVICE DESIGN. SO PART OF THIS DRAFT FRAMEWORK THEY LAID OUT AND GIVE BENEFITS TO IS FASTER STUDY RECRUITMENT, GREATER PARTICIPANT COMMITMENT SO LESS HIGHER RETENTION IN YOUR STUDIES AND BETTER PROTOCOL DEVELOPMENT. SO THAT WOULD STREAMLINE EVERYTHING MAKING YOUR DATA BETTER. THIS CAN APPLY EVERY STAGE OF THE RESEARCH. IF YOU ARE DOING CELLULAR BIOLOGY, IS IF YOU ARE DOING STUDYING NEURAL PLASTICITY IS THAT MEANINGFUL, WHAT KIND OF TRANSLATION WOULD THAT HAVE IN LONG SHOT, IS THAT GOING TO BE A MEANINGFUL OUTCOME, IS IT WORTH STUDYING IN THE FIRST PLACE ALL THE WAY TO OBVIOUSLY CLINICAL IMPLEMENTATION. >> WE ARE ALWAYS TRYING TO BALANCE THE CONCEPTS OF NEED FOR RESEARCH EFFICIENCY. ESPECIALLY WITH LIMITED BUDGETS AND NEEDING TO BE EFFICIENT WITH THE RESOURCES THAT WE HAVE. WITH COST AND PLANNING. ONE OF THE FIRST THINGS THAT OFTEN GOES OUT THE WINDOW IS THE COST OF BRINGING IN STAKEHOLDERS AND HAVING FOCUS GROUPS AND ENGAGING THESE INDIVIDUALS EARLY ON BOTH BECAUSE OF THE PRESSURES OF GETTING A STUDY UP AND RUNNING QUICKLY BUT ALSO THE RESOURCES AVAILABLE. SO WOULD WE BE BETTER OFF EMPHASIZING AND SHIFTING OUR PRIORITIES JUST A BIT MORE SO THAT WE INVEST IN THAT COST UP FRONT AND WE MAKE THAT A PRIORITY SO THAT WE END UP WITH A FINAL PRODUCT THAT'S MORE IMPACTFUL IN THE LONG RUN. IF WE PUBLISH A STUDY THAT DOESN'T NECESSARILY HAVE THAT POTENTIAL FOR TRANSLATION, IS IT REALLY IMPACTFUL AS IT COULD BE IF WE INVESTED THE TIME AND ENERGY. THE EXAMPLE THAT I HAVE IS WE HAVE WORKED A LOT ACROSS A VARIETY OF DIFFERENT POST ACUTE CARE SETTINGS. SO HOME HEALTH, SKILLED NURSING FACILITIES, OUTPATIENT, INPATIENT OPERATIONS, AND WE HAVE LOOKED AT QUESTIONS MORE RELATED TO PROGRESSIVE COMPLEX AND PERCEIVE AS FRAGILE AND UNABLE IN CLINICIAN EYES TO ENGAGE IN HIGHER SPENCETY APPROACHES TO INTERVENTION. ONE THING THAT WENT INTO FIRST IN TO THE CLINICAL FACILITIES IS INTERVIEW BE CLINICIANS AND ASK THEM FROM YOUR WORK FLOW STANDPOINT HOW IS THIS GOING TO FIT IN, WHAT ARE THE CONSTRAINTS, THE BARRIERS FROM A PRODUCTIVITY STANDPOINT WE CANNOT ALTER, THAT WE HAVE TO DESIGN THE FRAMEWORK FOR THIS INTERVENTION WITHIN THESE CONSTRAINTS. EACH CLINICAL FACILITY IS DIFFERENT. WE ARE ALSO CONTINUOUSLY THINKING AND INTERVIEWING THEM ABOUT THE SCALABILITY AND THINKING ABOUT TOWARDS A FUTURE, HOW WOULD I SCALE THIS ON A LARGER BASIS SO THAT I'M NOT TAILORING TO EACH INDIVIDUAL CLINIC BUT I HAVE PARAMETERS AND GUIDELINES. BUT IS THROUGH THOSE INTERVIEWS AN FOCUS GROUPS TYPESES OF DISCUSSIONS THAT WE GLEANED A LOT ABOUT WHAT WE SHOULD AND SHOULDN'T BE DOING AND MAKE SURE THE TEAM IS ENGAGEED FROM THE BEGINNING SO IT'S NOT JUST THE ACADEMIC RESEARCHER THAT'S COMING IN AN DROPPING THEIR IDEA WITHIN A CLINICAL ENVIRONMENT, IT'S MORE OF A TRUE WE LEARN FROM THEM AS MUCH AS THEY LEARN FROM US SCENARIO. >> WE ARE GOING TO BE TALKING ABOUT THE STUDY DESIGN HERE. WHEN YOU ARE FORMULATING YOUR RESEARCH QUESTIONS, IT IS IMPORTANT TO BRING CONSUMERS IN ON THAT. >> FROM THE VERY BEGINNING. >> THIS ASKING THEM TO COME INTO A LAB MEETING A MORE FOCUS GROUP TYPE OF PRESENTATION OR INTERACTION. THERE'S A LOT OF WAYS YOU CAN ENGAGE AS INDICATED HERE NOT JURIES PATIENTS BUT PROVIDERS PAYERS, POLICY MAKERS, IT IS IMPORTANT TO TREAT THEM AS CONSULTANTS SO IF THEY ARE COMING IN ONCE OR TWICE TO PROVIDE AN OPINION THAT'S FINE BUT AFTER THEY HAVE BEEN ACTIVELY PART OF YOUR TEAM THEY DESERVE TO BE PAID AS YOU WOULD ANY OTHER CONSULTANT. THEIR INPUT IS JUST AS IMPORTANT AS BIOENGINEER OR CLINICAL SPECIALIST YOU ARE ENGAGED WITH. MAKING SURE YOU BUILD THAT IN SO THEY SEE THE VALUE OF THAT INTERACTION SAME YOU TREAT OTHER CONSULTANTS. >> IT IS ONE THING INVITING SOMEBODY FOR ONE TIME MEETING. GETTING OFF THE TOP OF YOUR HEAD CONVERSATION GOING. BUT WHEN YOU START ASKING THEM TO DO WORK -- THEY SHOULD BE TREATED WE SHOULD BE TREATEDDED THE SAME AS ANY OTHER CONSULTANT. >> JUST GET A SENSE HAVING ENGAGED PATIENTS OR PROVIDERS IN SOME WAY SHAPE OR FORM IN THE FORMAT WE ARE DESCRIBING, BRINGING THEM TO A LAB MEETING AND PERFECT, GREAT. HAVING SOME SORT OF FORMAL ENGAGEMENT OR INFORMAL ENGAGEMENT. >> SO LITTLE STORY TIME WE HAVE SOME PAL BILLS HERE GOOD FOR MISSED OPPORTUNITY STORIES SO MY EXPERIENCE WRITING GRANTS HAVE BEEN REALLY GOOD. I THINK I HAVE ADDED A VERY UNIQUE PERSPECTIVE TO THE OVERALL GRANT APPLICATION ADVISING ON THAT. BUT THIS -- THE DOD SPINAL CORD INJURY RESEARCH PROGRAM GRANT PROGRAM, THEY ARE NOW REQUIRING CONSUMERS TO BE EVERY CLINICAL APPLICATION NEEDS CONSUMER ADVOCATE NOW. OR CONSULTANT. YEAH. I HEARD THE STORY LAST SUMMER WHERE ONE OF MY FRIEND CALLED ME AND THE RESEARCH TEAM DIDN'T EVEN SHARE THE ABSTRACT WITH THEM. THEY WANTED TO SIGN LETTER OF SUPPORT. I WAS LIKE DON'T DO IT. IT WAS PRETTY UPSETTING TO HEAR THAT. SO THAT'S A DEFINITE TOKENISM JUST TRYING TO GET THE CHECK MARK. SO MY EXPERIENCE WORKING WITH THE BILITEC (PHONETIC) I HAVE BEEN THERE SINCE DAY ONE, IT'S A LOT OF OUR ABASIC DESIGN AND CONSUMER REQUIREMENTS DEVELOPED CAME OFF PRETTY STRONG OPINION THAT I DON'T THINK OUR COMPANY HAVE THE SUCCESS THAT WE HAVE HAD WHEN STILL PRE-MARKET. BUT THE DESIGN REQUIREMENTS WE SET THE STANDARD TO, I DON'T THINK WE CREATED A PRODUCT MEANINGFUL,IT'S GOING TO CHANGE LIVES HOPEFULLY I THINK MY PERSPECTIVE ON THAT HELPED A LOT. I HAVE REVIEWED GRANTS FOR FIVE YEARS NOW. FOR THE STATE OF MINNESOTA AND STI -- THE CDMR PIECE SPINAL CORD PROGRAM, THAT PERSPECTIVE IN THE REVIEW ROOM I CAN'T SAY IT'S -- I KNOW I HAVE HAD A LOT OF PEER REVIEWERS COME UP TO ME AFTERWARDS AND SAYING I NEVER THOUGHT ABOUT IT THAT WAY. I REALLY WISH NIH INCLUDING CONSUMERISM THERE PEER REVIEW PROCESS. IT'S -- IT HAS A FRESH PERSPECTIVE AND DIFFERENT PERSPECTIVE WHICH I THINK THE OUTCOME IS TO HELP PEOPLE. I KNOW NIH HAS TRAINING OBJECTIVES. WE ARE TRAINING TO HELP PEOPLE AND THAT'S END OF THE DAY THAT'S WHAT MATTERS. HELP RIGHT NOW I'M NOT A PROJECT DEVELOPING A SURVEY FOR NEUROMODULATION. IT'S ALL CONSUMER DIRECTD WITH A FEW SCIENTISTS KIND OF ORGANIZING IT. BUT DEVELOPING THOSE RESEARCH QUESTIONS, I'M PRETTY OPTIMISTIC WE ARE GOING -- WHEN IT'S PUBLISHED IT WILL HAVE A BIG IMPACT IN THAT DIRECTION. SOME OTHER MISSED OPPORTUNITIES. I WAS ON A DIVERSITY INTEGRATION COUNCIL FOR A BUSINESS MINNEAPOLIS, BASICALLY IT WAS TO CHECK I WAS ON THERE AS A CHECKLIST AND THE AGENDA THE OUTCOMES ARE SET BEFORE THE MEETING TOOK PLACE. I HAD A LOT OF THINGS TO SAY, I NEVER GOT LISTENED TO SO I STOPPED SHOWING UP. IT'S UNFORTUNATE. THAT COMPANY STILL HASN'T CHANGED TO HELP PEOPLE. DO BETTER. THERE IS A PROJECT I WAS ON FOR TWO YEARS IT WAS CONSUMERS AND AND SOME OF THE LEADING SCIENTISTS IN THE FIELD. THERE IS A BIG CLASH OF OPINION IT WAS FOR CONSUMER RESOURCE FOR PEOPLE WITH SPINAL CORD INJURIES. RYING TO SAY THIS WITHOUT IDENTIFYING IT BUT THERE WAS A CLASH BEFORE IT WAS LAUNCHED AND UNFORTUNATELY WE THE CONSUMERS SPLIT AND SCIENTISTS WENT A DIFFERENT WAY. IT WAS UNFORTUNATE BECAUSE IT'S A GOOD RESOURCE, IT'S OUT NOW BUT THERE WOULD HAVE BEEN GOOD TO HAVE EVERYBODY WORK TOGETHER. SOL ONE OF THE I THINK ONE OF THE BARRIERS WE IDENTIFIED IS HOW DO YOU FIND IF YOU ARE STRICTLY A RESEARCH SCIENTIST, HOW DO YOU FIND PEOPLE? SEW OBVIOUSLY PATIENT REPRESENTATIVE ORGANIZATIONS YOU HAVE A LOCAL OR REGIONAL ONE EVEN BETTER THEN YOU CAN SEND SOMEBODY TO A DIFFERENT STATE BUT EVEN NATIONAL ONE CONSIST TRY TO MATCH YOU WITH SOMEBODY LOCALLY. THERE ARE ON LINE FORUMS, FACEBOOK GROUPS, PROBABLY EVERY DISEASE CONDITION THERE IS A GROUP OUT THERE CHATTING ABOUT CONDITION, THERE'S SPINAL CORD INJURY, ON LINE FORMS TO TRY TO RECRUIT SOMEBODY. IN A COMMUNITY GATHERING PLACES, ADAPTIVE FITNESS CENTERS FOR SPINAL CORD INJURY, WE HAVE FOR -- WE STARTED OUT WITH A BUNCH OF ADVOCATES WORKING OUT TOGETHER WITH SPINAL CORD INJURIES. WE WERE VERY MOTIVATED PEOPLE THERE SPINAL CORD INJURY COMMUNITY ARE MOTIVATED TO DO SOMETHING TO FURTHER PHYSICAL CONDITION. CLINICIANS YOU CAN ALWAYS GIVE THEM A HAND OUT OR A CARD, OBVIOUSLY THERE'S HIPAA CONCERNS BUT THEY CAN GIVE YOU THEIR -- YOUR INFORMATION PATIENT HAS OPTION TO CONTACT YOU SOCIAL MEDIA AGAIN PARTICIPANTS. >> SO OFTEN THE PARTICIPANTS HAVE BETH CONNECTIONS WHERE TO FIND OTHER PARTICIPANTS. >> THIS IS JUST A -- WE HAVE A FEW EXAMPLES HERE, THIS IS THE SPINAL CORD STIMULATION FOR SPINAL CORD INJURY STUDY. THEY CREATED THEIR OWN WEBSITE FOR RECRUITMENT AND THAT'S JUST ONE WAY TO RECRUIT PEOPLE. SOCIAL MEDIA, GENERATING BUZZ ABOUT YOUR RESEARCH, MORE EXCITED PEOPLE ARE ABOUT IT, THE MORE LIKELY WILL GIVE RECRUIT AND GET PEOPLE EXCITED ABOUT COMING IN AND HELPING. GOOD OBVIOUSLY WANT TO PROVIDE GOOD INTERACTIONS, MAKE IT CONVENIENT WHEN WE CONTACT THEM EFFICIENT PROFESSIONAL WITH YOUR STUDY VISITS, TRAVEL ANYTHING YOU CAN DO TO MAKE IT EASIER IF YOU YOU HAVE A PARKING RYE TO GET PARKING VOUCHERS OR SCHEDUE IT FOR THEM AND A LOT OF HEALTHCARE SYSTEMS ARE PARTNERING WITH LYFT OR UBER TO BRING PEOPLE INTO THEIR HOSPITAL SO IF THEY NEED HELP WITH TRANSPORTATION, THAT'S ONE WAY. TO GET THEM OUT OF THEIR HOME AND INTO YOUR LAB OR YOU CAN VISIT THEM OR DO IT OVER ZOOM OR TELECONFERENCE SYSTEM KEEP FOSTER AFFILIATION, NEWS LETTERS, JUST GENERATE GENERAL EXCITEMENT BUZZ ABOUT YOUR RESEARCH IS A GOOD WAY TO DO THAT. I ALWAYS THINK ABOUT IMPROVING AND HOW CAN I DO THAT BETTER. I ALWAYS THINK AM I TARGETING OUR POPULATION THE RIGHT WAY OBVIOUSLY IF SOMEBODY IS BLIND YOU NEED TO FIGURE OUT HOW TO >> WE SHIFTED THE FOCUS OF OUR TESTING TO PATIENT HOMES ENTIRELY SO WE WOULDN'T HAVE TRANSPORTATION BARRIERS, FOR MEDICALLY COMPLEX INDIVIDUALS, WHILE THAT POSES A TREMENDOUS CHALLENGE FROM OUR TEAM GOING OUT AND BEING ABLE TO REACH WITHIN A LARGE RADIUS, IT HAS DECREASED THE REFUSAL RATES IN TERMS OF PATIENTS WILLINGNESS TO ENGAGE IN RESEARCH. THIS IS AN EXAMPLE OF A STAKEHOLDER ENGAGEMENT BOARD OR GROUP THAT -- ASSOCIATE DIRECTOR FOR EDUCATION EVALUATION HAS PUT TOGETHER HAS BEEN A SUCCESSFUL GROUP OF VETERANS THAT HELP INFORM RESEARCH. HOW MANY PARTICIPATED IN A FORMAL STAKEHOLDER ENGAGEMENT TEAM AS A RESEARCHER COMING IN FOR FEEDBACK OR AS A PARTICIPANT AS A REPRESENTATIVE OF A PATIENT POPULATION OR PROVIDER. A GOOD HANDFUL. SO THE WAY THIS WORKS, THERE'S LOTS OF WAYS TO DO THIS OBVIOUSLY THIS IS A MORE FORMAL PROCESS IN THE WAY THIS IS CONSTRUCTED. VETERANS MEET WITH THE RESEARCHERS ON A REGULAR BASIS THROUGH A STRUCTURED FORMAT. THE VETERANS RECRUITED WE HAVE A VARIETY OF VETERANS WITH DIVERSE PERSPECTIVES, SO SELECTING THIS DIVERSE GROUP IS A CRITICAL ELEMENT YOU CAN SEE A VETERAN WHO IS A NATIVE AMERICAN WEARS MULTIPLE HATS IN TERMS OF BROAD REPRESENTATION FROM A DIVERSITY STANDPOINT. THE INDIVIDUALS UNDERSTOOD GO A 20 TO 30 MINUTE INTERVIEW, I PASSED AROUND HAND OUTS THAT DEMONSTRATE SOME OF THE EXAMPLES THAT HAVE COME OVER THE PAST YEAR I THINK 2018 AND PRODUCTS AND SOME OF THE CHANGES THAT WERE RESULT OF SOME OF THE INPUT RECEIVED. SO THE VETERANS SELECTED GET TO KNOW EACH OTHER, THEY HAVE ORIENTATION, EXPECTATIONS ARE LAID OUT IN TERMS OF COMMITMENT AND THEN THEY MEET MONTHLY, SO THEY MEET WITH DIFFERENT CLINICAL RESEARCHERS ON A MONTHLY BASIS FOR AN HOUR DISCUSSING A NEW TOPIC FACILITATED AND THEN ALSO GOING BACK AND REVIEWING SOME OF THE PREVIOUS TOPICS THEY BROUGHT TO THE TABLE OR THAT HAVE BEEN BROUGHT TO THEM AND GIVING THEM FEEDBACK HOW THEIR INPUT BENEFITED OR CHANGED THE COURSE OF A CLINICAL STUDY. SO THAT IS A KEY ELEMENT SO I THINK A LOT OF TIMES WE GET INPUT, WE GET FEEDBACK BUT WE DON'T ALWAYS CIRCLE BACK TO THE PARTICIPANTS AND TELL THEM WHAT THE VALUE WAS OF THEIR INPUT SO WE KEEP THEM ENGAGED LONGER TERM. SO THAT'S BEEN A KEY ELEMENT AND YOU WILL SEE THAT IN THE HAND OUT REPRESENTED THERE. THEN SO THAT'S KIND OF A THE BOTTOM PART HERE THE REGULAR FEEDBACK PIECE. SIX MONTHS LATER THERE IS THIS FORMAL PROCESS WHERE THE FACILITATOR REACHES OUTS THE INDIVIDUALS PRESENTED TO THIS BOARD TO THIS GROUP OF VETERANS AND ASK THEM FOR SPECIFIC EXAMPLES HOW THEIR UNPUT CHANGED THE COURTS OF WHAT THEY WERE DOING. OVER THE COURSE OF WHAT WE WERE DOING. IT WAS NOT THE ONLY WAY, THERE'S LESS FORMAL WAYS OF STAKEHOLDER INPUT WE DESCRIBED A LITTLE BIT AND THAT YOU WILL ELABORATE ON A LITTLE BIT MORE AS WELL. >> A FEW YEARS AGO WE WERE -- OUR COMPANY IS DEVELOPING A POWERED GLOVE. BUT WE DID A FOCUS GROUP WITH PEOPLE WITH SPINAL CORD INJURY WE DEVELOP THIS SET OF QUESTIONS AND WENT IN FOR 90 MINUTE MEETING. WHAT ADLs DO YOU WANT TO DO, CHALLENGES WITH -- THAT YOU HAVE AND SO ON. IT WAS AN INTERESTING CONVERSATION. THE MEETING -- WE ARE OUT IN THE PARKING LOT CHATTING AFTERWARDS AND AND MY FRIEND TOM WHO IS A QUADRIPLEGIC TRANSFERS INTO VOLKSWAGEN. THAT'S THEN LIKE A REALLY INTERESTING CONVERSATION DEVELOPED OFF THAT. O TRANSFERRING YOUR CAR AND DRIVING IS SOMETHING THAT WE DIDN'T THINK ABOUT. CHANGING A SETTING, OPEN END MAKING YOUR QUESTIONS OPEN ENDED, SOMETIMES NOT HAVING SOME TIME WHERE THERE'S NO FRAMEWORK FOR QUESTIONS, YOU CAN DEVELOP A GENERAL CONVERSATION THAT HAPPENS ORGANICALLY. AND HE'S LIKE I WISH I COULD TURN SCREWDRIVER OR PLAY TENNIS. SEE IF -- DOESN'T HAVE GRIP STRENGTH. SO ALL THESE THINGS WE DIDN'T THINK ABOUT LEADING UP TO THAT, MY PROBLEMS START WITH MY SHOULDER. AND SO I THINK IT'S IMPORTANT TO OPEN END UNSTRUCTURED TIME DOING FOCUS GROUPS TOO. OBVIOUSLY OUR QUESTIONS ARE IMPORTANT BUT HOW DO YOU GET THESE THINGS THAT REALLY THINK ABOUT. >> THE PARKING LOT CONVERSATIONS THAT OFTEN LEAD TO THE GREATEST INNOVATIONS. WE ARE GOING TO OPEN UP THE FLOOR TO OTHER EXAMPLES AND THINGS Y'ALL MIGHT HAVE EXPERIENCED ALONG THOSE LINES, WE CAN DO THAT NOW, OR WAIT UNTIL THE END OF THE PRESENTATION BUT WE ARE THINKING EXAMPLES THAT Y'ALL HAVE OF WHAT'S WORKED BEST IN YOUR ENVIRONMENT, FORMAL, INFORMAL WHAT TYPES OF ENGAGEMENT ARE MOST SUCCESSFUL. AND OBVIOUSLY WHEN WE THINK ABOUT DIVERSITY IN TERMS OF INCLUDING A DIVERSE BODY OF STAKEHOLDERS WE HAVE A NUMBER OF CONSIDERATIONS THAT ARE PART OF THE EQUATION HERE. CERTAINLY ETHNIC AND RACIAL REPRESENTATION WHICH OFTEN INFLUENCES HEALTH BELIEFS AND LIFE PRIORITIES, THOSE TWO ARE CLOSELY TIED IN MANY WAYS. THINKING ABOUT SOME INDIVIDUALS MAYBE MORRETTE SENT TO PARTICIPATE IN TERMS OF CULTURAL OR HISTORICALLY INVOLVEMENT IN DIFFERENT ASPECTS OF THINGS LIKE RESEARCH THEY MAY BE MORE HESITANT. SOCIOECONOMIC BARRIERS POSE A HUGE BARRIER FOR INDIVIDUALS TO ACTIVELY PARTICIPATE IN RESEARCH, CERTAINLY ISSUES ASSOCIATED WITH GENDER AND SEX IN TERMS OF MAKING SURE THERE'S BALANCED REPRESENTATION TO REFLECT DIVERSITY. WE MENTIONED BARRIERS TO PHYSICALLY ACCESSING MATERIALS, IF YOU HAVE SOMEONE WHO HAS VISUAL IMPAIRMENTS YOU HAVE TO MAKE SURE YOU HAVE A LARGE FONT OR ALTERNATIVE VERSION OF YOUR HAND OUTS AVAILABLE AS WELL AS OTHER PHYSICAL FROM A DISABILITY STANDPOINT OTHER PHYSICAL LIMITATIONS THAT WOULD ALLOW THEM TO APPROPRIATELY ACCESS THE MATERIALS THAT ARE NECESSARY IN ORDER TO ENGAGE IN THE RESEARCH STUDY, HEALTH LITERACY AND EDUCATION PLAY A LARGE ROLE, WE KNOW THAT LACK OF DECREASED HEALTH LITERACY AND EDUCATION ARE GOING TO CHANGE CERTAINLY SOMEONE'S PERCEPTION AND INPUT THEY ARE GOING TO PROVIDE WILL BE DIFFERENT. SO MAKING SURE THOSE INDIVIDUALS ARE ALSO REPRESENTED AT TABLE IS IMPORTANT. HERE IS A CLASSIC PICTURE OF THIS CONCEPT OF RESEARCH, PEEN ROLL GUINEA PIGS IN PA CAGE BEING -- PEOPLE ARE GUINEA PIGS IN CAGE BEING WATCHED AND PRODDED. WHETHER OR NOT WE CAN CHANGE THIS PERCEPTION WE CAN OVER TIME BY ENGAGING STAKEHOLDERS HAVING THEM SHARE THE EXPERIENCES IN WAYS THAT OTHER PEOPLE UNDERSTAND THE VALUES OF THE RESEARCH PROCESS. THERE WAS A LARGE META ANALYSIS DONE THAT SAID THAT 93% OF INDIVIDUALS WHO PARTICIPATE IN RESEARCH WOULD LIKE TO KNOW RESULTS OF STUDIES OR WHAT THEY ENGAGED IN, THE FINAL PRODUCT OF THE STUDIES. DO YOU KNOW HOW MANY PEOPLE GET THOSE RESULTS? LESS THAN SO 10% GET THE RESULTS BACK TO THEM. SO 90% REPORT THEY NEVER HEAR THE FINAL RESULT OF THE STUDY THEY PARTICIPATED IN. SO RIGHT THERE WE ARE LOSING PEOPLE AND ENGAGEMENT IN TERMS OF ENTHUSIASM FOR FUTURE PARTICIPATION BECAUSE THEY NEVER REALLY SEE THE VALUE OF HOW THEY PARTICIPATED. >> WHO HERE FOLLOWS UP AND SHARE AS PUBLICATION, WITH THEIR PARTICIPANTS AFTERWARDS. >> THERE IS GREATER EMPHASIS, WE HAVE NIH REPORTER WHERE WE ARE REPORTING RESULTS OUT AND THAT'S ONE MECHANISM. BUT MAILING OUT THE FINAL RESULTS TO ALL PARTICIPANTS WITH A LETTER THAT SAYS HEY THANK YOU FOR PARTICIPATING, IT'S BEEN FOUR YEARS SINCE YOU ENROLLED IN THE STUDY BUT HERE ARE THE RESULTS. WE GREATLY VALUE FOR ROLE IN THE RESEARCH PROCESS SO THAT'S THE WAY WE ENGENDER MORE INVOLVEMENT ENGAGEMENT AND GET AWHICH FROM THIS STEREOTYPE THAT RESEARCH IS ABOUT BEING A GUINEA PIG. >> DID WE PUT IT IN OUR CONSENT? MAILING IT BACK OUT. WE DO NOT FORMALLY I DON'T THINK PUT IN OUR CONSENT FORM LIKE YOU ARE SAYING YOU WILL RECEIVE INFORMATION? >> YOU INFORM AT THE FRONT END WHEN THEY ARE CONSENTED, THAT THEY ARE GOING TO GET, RECEIVE RETURN RESULTS. >> YES, CORRECT. >> THE POINT IS THEY HEAR IT. >> I DON'T THINK IT'S FORMALLY WRITTEN INTO OUR CONSENT FORM BUT WE DO MENTION IT IN TERMS OF THIS STUDY IS THIS LENGTH OF TIME WHERE THIS FAR INTO THE STUDY YOU WON'T HEAR FROM US FOR A NUMBER OF YEARS UNLESS THEY ARE PART OF THE NEWS LETTER GROUP OF PEOPLE THAT ARE FOR CERTAIN STUDIES, YOU MAY NOT HEAR FROM US FOR THREE YEARS BUT WE WILL SEND YOU THE FINAL PRODUCT. AND KEEP IN TOUCH WITH US, IF YOUR ADDRESS CHANGES AND YOU WANT TO SO WE CAN SEND IT OUT TO YOU THREE OR FOUR YEARS DOWN THE ROAD. IT HAS BECOME AN IMPORTANT PART OF HOW WE THEN ENGAGE THEM TO COME OUT TO FUTURE STUDIES OR ENGAGE INDIVIDUALS TO SEEK OUT THEIR NEIGHBORS FRIENDS OTHER INDIVIDUALS WHO MIGHT BE CANDIDATESTOR MA WE ARE DOING -- FOR WHAT WE ARE DOING. >> I THINK YOU HIT THE NAIL ON THE HEAD AND YOU ARE CORRECT. BUT PART OF SHARING THE OUTCOMES, THE FINDINGS, ALL STARTS FROM ENGAGING THEM IN THE FIRST PLACE. IF THEY ARE A PART OF ALL THE PROCESSES YOU LISTED, THEN NATURALLY THEY WOULD BE PART OF THE OUTCOME AND RESULT BECAUSE YOU GIVE THEM UPDATES ON REGULAR PROGRESS, YOU WILL GET THEM INVOLVED IT BECOMES A PRACTICAL THING FOR YOU AND THEM AS IN PROBLEM SOLVING OR IDENTIFYING WHAT THE PROBLEM IS RATHER THAN JUST A RESEARCH ACTIVITY. >> I WILL SAY THERE ARE CERTAINLY SOME LIMITATIONS TO WHAT WE CAN SHARE, WE ARE CAREFUL ABOUT NOT OVERLY SHARING RESEARCH RESULTS BEFORE WITH AN INDIVIDUAL PARTICIPANT SO WE HAVE THIS DISCUSSION ALL THE TIME, A PATIENT FINISHING ONE OF OUR STUDIES AND THEY WANT THE MRI RESULTS, THEY WANT TO KNOW WHAT THEIR FUNCTIONAL IMPROVEMENT WAS, I CAN SHARE THAT ON AN INDIVIDUAL LEVEL AFTER THEY FINISH THE STUDY BUT I CAN'T SHARE IT AT MIDPOINT, THEY IMPROVE BY X PERCENT BECAUSE THAT CAN BIAS THE RESULTS THEY SEE THE QUAD STRENGTH ON LEFT SIDE IS WEAKER THAN RIGHT SIDE THEY WILL WORK ON THE LEFT SIDE SO WE HAVE TO TO BE CAREFUL WHAT TYPE OF INFORMATION WE GIVE THEM THOUGH WE KNOW THAT OUR PARTICIPANTS ARE ASKING FOR THIS INFORMATION EVERY SINGLE TIME THEY COME IN SO A LOT OF TIMES IT'S MESSAGING WE TELL THEM WE LOVE TO SHARE MORE INFORMATION, HERE IS WHAT WE CAN SHARE AT THIS POINT IN TIME BUT WE WILL YOU DETAILS, DATA WHEN YOU FINISH THE STUDY. SOME IS TRANSPARENCY HELPING UNDERSTAND WHY WE CAN'T SHARE CERTAIN THINGS. >> ONE THING AT SITE LEVEL INVESTIGATOR NIH IS SPONSOR ONE THOUGHT COULD BE FOR RELATED AREAS, THE PI WRITES A LAY PERSON SUMMARY OR ABOUT RACKET, THIS COULD BE COMPILED BECAUSE OBVIOUSLY AS SPONSOR YOU CANNOT CONTACT THE PATIENT DIRECTLY YOU CAN CONTACT THEM TO THE SITE BUT HA IS A USEFUL ADDED BENEFIT AS SAY THERE'S SEVERAL SPINAL CORD INJURIES, STUDIES GOING ON. YOU WRITE A LAY PERSON SUMMARY SENT OUT TO A NEWS LETTER TO THE SITES AND DEMONSTRATE WHAT NIH IS DOING COLLECTIVELY AND OBVIOUSLY YOU HAVE A ONE ON ONE INTERACTION YOU SHOW MRIs AND THINGS LIKE THAT BUT THAT IS AN INVESTIGATOR TO PATIENT INTERACTION. >> YOU ARE RIGHT. YEAH. WHEN WE SEND OUT OR LETTERS WE HAVE A COVER ABSTRACT EQUIVALENT, OF AN EXPLANATION, HERE IS THE PUBLICATION SO YOU CAN SOME OF OUR PARTICIPANTS WANT TO SEE THAT FINAL PUBLICATION BUT MANY WON'T HAVE THE HEALTH LITERACY OR SCIENTIFIC KNOWLEDGE TO FULLY EVALUATE THE ASPECTS SO HERE IS THE LAY EQUIVALENTS SO THEY CAN APPRECIATE THE FINDINGS. >> I WANT TO ASK IF YOU HAVE THOUGHT HOW TO ADDRESS THIS ISSUE OF BIAS A LITTLE BIT MORE. THIS IS A PROCESS THAT I'M ACTIVELY ENGAGED IN AND I AM IN FULL SUPPORT WE HAVE A LARGE CLINICAL TRIAL WE TRIED TO PUT TOGETHER A BODY OF STAKEHOLDERS AND HAVE THEM AND BE INVOLVED AT EVERY LEVEL OF THE TRIAL. ONE OF THE CHALLENGES WE FACED IS HOW TO MANAGE THE BIAS THAT FACEBOOK CAN HAVE A POSITIVE INFLUENCE ON RECRUITMENT BUT FAMILIES ARE PARTICIPANTS ARE DISCUSSING VARIOUS GROUP ASSIGNMENTS ON FACEBOOK THEN THAT INTRODUCES A LEVEL OF BIAS TO THE STUDY THAT WE CAN'T CONTROL. SO YOU EITHER HAVE TO COMPLETELY SEPARATE IT AND SAY OKAY THE INVESTIGATORS ARE NOT GOING TO BE INVOLVED, BUT THEN IF YOU WANT TO INCLUDE THE PARTICIPANTS AT THE LEVEL ALMOST OF AN INVESTIGATOR YOU ALMOST HAVE TO EDUCATE THEM ABOUT ALL THE LEVELS OF SCIENTIFIC RIGOR. SO THERE'S THIS BALANCE OR CHALLENGE, IT'S A BARRIER. ONE OF THE THINGS I WONDER IS IF WE CAN DO A BETTER JOB INFORMING PARTICIPANTS ABOUT THE SPECIFIC NEEDS SCIENTISTS FACE, I DON'T KNOW IF YOU THOUGHT ABOUT THOSE CHALLENGE AS LITTLE BIT MORE. >> GREAT COMMENT. WE DO SPEND A LOT OF TIME RYING TO EDUCATE OUR PARTICIPANTS ON THE FRONT END AS TO WHAT WE CAN TELL THEM, WHAT WE CAN'T, WHAT THEY CAN SHARE WITH OTHER PEOPLE SO FOR EXAMPLE IF THEY RECEIVE A REHABILITATION INTERVENTION AND GOING INTO OUR GATE LAB TO UNDERSTOOD GO MOVEMENT ASSESSMENT WE HAVE TO EDUCATE OUR PARTICIPANTS TO NOT MENTION ANYTHING ABOUT THE SPECIFICS OF THE INTERVENTION THEY RECEIVED, THERE ARE KEY ELEMENTS OF SOMETHING THEY MIGHT SAY THEY INCLUDE THE ASSESSORS INTO WHAT GROUP ASSIGNMENT. SO FROM A BLINDING STANDPOINT WE SPEND TIME TRYING TO HELP THEM UNDERSTAND WHY THEY HAVE TO BE CAREFUL ABOUT THOSE CONVERSATIONS. WE HAVEN'T HAD A LOT OF ISSUES WITH FACEBOOK BUT I CAN SEE HOW YOU CAN PROBABLY HAVE THE SAME TYPES OF CONVERSATION AND SAY LISTEN, UNTIL THE STUDY IS COMPLETE WE NEED YOU TO NOT TALK ABOUT THE SPECIFICS OF WHAT YOU ARE ENGAGED IN AND HAVE AND EXPLAIN WHY IN MORE DETAIL. FOR THE MOST PART WE HAVE HAD GOOD ASSESSMENT WITH INTERVENTIONISTS HAVING PATIENTS NOT SPILL THE BEANS. EVERY ONCE IN A WHILE WE HAVE A PATIENT WHO SAYS SOMETHING THEY'RE NOT SUPPOSED TO SAY. >> >> THAT'S WHY YOU HAVE NDAs I THINK. >> WITH PARTICIPANTS WE DON'T USUALLY -- WE DON'T HAVE THEM SIGN AN NDA PER SE, WITH CONSULTANTS AND THOSE GROUPS FOR SURE. THE PARTICIPANTS. >> THERE'S CONFIDENTIALITY AGREEMENTS, I KNOW PEOPLE THAT SIGN THAT. >> I GUESS YOU COULD HAVE A PARTICIPANT SIGN IT. THE MORE IMPORTANT THING IS TO HAVE THAT CONVERSATION AND EXPLAIN THE WHY AND HOW IT IMPACTS THE STUDY IN TERMS OF GETTING THE BUY IN PROBABLY. >> ANOTHER THINK YOU THINK ABOUT BIAS, THE AGE OLD QUESTION, DOES THIS SHIRT LOOK GOOD ON ME, OF COURSE IT LOOKS GREAT. IS THIS RESEARCH QUESTION, IS THIS DEVICE GOOD. HOW DO YOU GET CONSUMER TO BE HONEST. SO THAT IS SOMETHING YOU NEED TO ENCOURAGE THEM TO BE HONEST, ASK THE QUESTION YOU WANT TO HEAR. Q. REALLY GOOD POINT. THERE IS A TENDENCY TO WALK IN THE DISCUSSION AND FEEL LIKE THEY OWE IT TO YOU TO STICK WITH WHATEVER PRODUCT YOU PROPOSE. >> WHEN IT COMES TO ENGAGING THESE PARTICIPANTS WE ALSO USE PARTICIPANTS ON THE BACK END FOR INTERPRETATION DISSEMINATION OF RESEARCH FINDINGS. IF A TRIAL IS NEGATIVE, DO YOU THROW EVERYTHING OUT THE WINDOW? THE THERE'S MULTIPLE SCHOOLS OF THOUGHT ON THAT. BUT WE HAVE REALLY GONE THROUGH THOUGH AND LOOKED AT AND TALKED TO INDIVIDUALS WHETHER IT'S PROVIDERS, WHETHER IT'S PATIENTS, WE HAVE HAD FOCUS GROUPS AND DISCUSSIONS TO TRY AND IDENTIFY WHAT WERE THE CAULKER TICKS OF FACILITY OR THOSE PROVIDERS OR THOSE PATIENTS THAT ALLOW THEM TO SUCCEED WITH THIS INTERVENTION OPPOSED TO THE ONES THAT DIDN'T. SO WE GLEAN A LOT OF O INFORMATION THAT INFORMS THE NEXT STEPS. SO THAT'S I THINK THE -- HAVING ENGAGEMENT STOP WHEN STUDY IS OVER AND SENDING OUT THE RESULTS MIGHT NOT BE ENOUGH. IF YOU CAN HAVE THEM TELL YOU WHAT WAS IT THAT WAS A BARRIER TO REALLY BEING ABLE TO PERFORM THE HIGHER INTENSITY EXERCISE, WHAT ARE THE TYPES OF THINGS THAT GOT IN THE WAY AND FROM BOTH PROVIDER AND PATIENT LEVEL THAT REALLY MAKES THE NEXT STEPS A LITTLE BIT CLEARER AND MAYBE A LITTLE BIT MORE TARGETED TO THE RIGHT -- ANSWERING THE RIGHT QUESTION. DISSEMINATION OBVIOUSLY WE TALKED ABOUT SOCIAL MEDIA AND LOTS OF DIFFERENT AVENUES FOR DISSEMINATING STUDY FINDINGS. BUT REALLY THE PARTICIPANTS HELPING YOU GET THE WORD OUT BECAUSE THEY ARE THE ONES CONNECT TO THE ADS VOW CHASSI GROUPS AND NETWORKS. AND ADVOCACY GROUPS AND NETWORKS AND SPREADING THE WORD FASTER TO SHORTEN THAT 17 YEAR TIME LINE. >> PART OF YOUR PUBLICATION DISSEMINATION, PLAN SHOULD INCLUDE CONSUMERS, A LOT OF WHEN YOU ARE GENERATING A MANUSCRIPT, WHO IS THE REALLY GOING TO EFFECT, WHAT IS -- WHAT KIND OF OUTCOMES, ARE YOU TRY FOG PLEASE JOURNAL REVIEWERS OR THE OVERALL COMMUNITY? IT'S ALL OF THE ABOVE. OBVIOUSLY HOPEFULLY YOU GET MORE FUNDING IF YOU GET SUCCESS ON YOUR FIRST PROJECT OR PROJECT LEADING UP TO THE NEXT ONE. THE GOAL AT THE END OF THAT CYCLE SHOULD BE SOMETHING IMPLEMENTED INTO CLINICAL SETTING. SO THAT IS SOMETHING TO CONSIDER. BRINGING CONSUMERS TO CONFERENCES, PLAYING THAT INTO YOUR TRAVEL BUDGET SO ON I HAVE SEEN SOME CONFERENCES NOW THAT ARE HAVING CONSUMER PANELS WHO WILL PRESENT RESEARCH WITH SOMEBODY THAT PARTICIPATE IN THE TRIAL. IT HAS A REALLY UNIQUE PERSPECTIVE I'M SURE. >> KEN MENTIONEDNA YESTERDAY AT COUNCIL, THE FACT THERE'S MORE BRINGING IN A PARTICIPANT TO TELL THEIR STORY. ABSOLUTELY. >> HAD OOH QUICK QUESTION FOR YOU, ROB. INITIALLY I THOUGHT EVERYONE ANSWERED THE QUESTION BUT WHEN YOU HEAR ABOUT A SERIES OF SAY FAIL SPINAL CORD INJURY STUDIES, DOES THAT END UP BEING A BLACK HOLE OF UNCERTAINTY AND DOES THAT AFFECT YOUR WILLINGNESS TO PARTICIPATE IN ANOTHER STUDY IF IT'S NOT EXPLAIN WHAT THE BENEFIT OR LEARNINGS WERE? >> I THINK WHAT -- THERE'S OBVIOUSLY A LOT OF SPINAL CORD INJURE -- INJURY. THE THING THAT DISCOURAGES MYSELF AND MY PEERS IS WHEN YOU KNOW IT'S A BLACK HOLE AND THAT RESEARCHERS SO DEDICATED TO THAT LINE OF RESEARCH. OR THAT SPECIFIC INTERVENTION THAT THEY KEEP PUSHING IT AND PUSHING IT. THAT'S WHERE IT'S FRUSTRATING BECAUSE THEY ARE GOOD INVESTIGATORS. THE THING THEY ARE SOLD ON IS NOT GENERATING THE OUTCOMES WE WANT TO SEE. YEAH. SO I THINK THAT IS MORE THAN TRUST. BUT AGAIN, FROM PEOPLE IN OUR COMMUNITY THAT KNOW MORE, PROBABLY NOT WITH THE GENERAL POPULATION BUT THAT TRICKLES DOWN. >> I WANT TO ADD ON FROM OUR PERSPECTIVE WE DEAL WITH ANXIOUS APPLICANTS AND YOU ARE EXACTLY RIGHT, THEY WANT TO GET THIS PROPOSAL IN AND YOU BRING UP THIS VALIDITY CHECK THIS REALITY CHECK AND IT'S LIKE TALKING TO A STATISTICIAN IN A GRANT DUE IN A WEEK AND SAY CAN YOU HELP JUSTIFY SIX PATIENTS IN EACH GROUP. >> THEY DON'T REALIZE THEY SHOOT THEMSELVES IN THE FOOT IF THEY ONLY HAVE TO REVISE IT AND REVISE IT, IN THE PEER REVIEW PANEL, THEY GET CALLED ON IT BECAUSE THEY DON'T HAVE THAT BUT CONVERSELY IF THEY HAVE HAD A FOCUS GROUP YOU CAN ALMOST SEE THE RESPECT REVIEWERS HAVING MORE RESPECT FOR THEIR THOUGHT PROCESSES AND IT HELPS THEM AND I HAD ANOTHER THOUGHT, IT REMINDED ME TO THE INITIAL STATEMENT ABOUT 17 YEARS, ROB HOW MUCH OLDER IN 17 -- NO. BUT I WONDER IF IT WILL BE A GREAT THESIS FOR THOSE STUDIES THAT ARE INCORPORATED CONSUMER INPUT IN THE BEGINNING DO THEY HAVE A MUCH SHORTER TRANSLATION 17 YEARS. >> THAT'S THE HOPE IT CAN BE FORMALLY STUDIED IN A DECADE WHEN WE COMPARE THEM TO TRANSLATION HOPEFULLY IMPROVES BY AT LEAST SHORTENS DOWN TO 8 TO 10 YEARS INSTEAD OF 17 IF NOT MORE. >> I HAVE A FOLLOW-UP TO ROB TO AL'S QUESTION. THAT IS AND THIS IS FOR ROB. MAYBE YOU WANT TO THINK ABOUT IT BEFORE -- FEEL LIKE YOU NEED TO ANSWER RIGHT AWAY. MAYBE LATER IN THE DISCUSSION SECTION. BUT ONE THING I STRUGGLE WITH EARLIER IN MY CAREER, FOCUSED ON MEKISTIC QUESTIONS AND MY COLLEAGUES IN SPINAL CORD INJURY RESEARCH STRUGGLE WITH WHEN YOU ARE DOING RESEARCH THAT IS INTENDED TO ANSWER MORE BASIC QUESTIONS ABOUT MECHANISM YOU DON'T REALLY EXPECT SOMEONE WILL BE ABLE TO SEE IMPROVEMENT IN THEIR HAND FUNCTION OR WALKING FUNCTION. WHAT IS THE WAY WE COULD ENGAGE PEOPLE CONSUMERS MORE IN THAT KIND OF RESEARCH THAT WOULD BE MEANINGFUL OR IS THAT AN AREA WHERE WILL INFORM RESULTS AND MAYBE WHEN WE GET O THE POINT WE INCLUDE YOU IN STUDIES WHERE WE ARE GOING TO APPLY IT TO FUNCTIONAL OUTCOME. >> OBVIOUSLY I THINK GENERATING QUANTITATIVE DATA IS EASY. MECHANISTIC TYPE THINGS, IMPROVEMENT IN -- LIEU CHANGE OF MMT SCORES OR SOMETHING. THAT'S SOMETHING EASY TO MEASURE AND SHOW PROGRESS OR HOWEVER IT'S PERFORMING. WHAT DOES THAT MEAN TO THE INDIVIDUAL? I'M STARTING TO THINK GRANT APPLICATIONS SHOULD HAVE CONSUMER QUOTES LIKE THIS RESEARCH WOULD MEAN X TO ME IF THIS OUTCOME HAPPENED. OR IF YOU HAVE SOME DATA FROM BEFORE COLLECTING OPEN ENDED COMMENT PUTTING THIS DEVICE ON A LOT, THAT KIND OF INFORMATION BELONGS JUST AS VALUABLE IF NOT MORE QUALITATIVE DATA IS JUST AS VALUABLE AS QUANTITATIVE AND MECHANISTIC, AT THE END OF THE DAY IS SOMEBODY INTEREST IN USING I. IS THAT TRULY GOING TO HELP THEM IMPROVE THEIR LIVES AND THEIR HEALTH. Q. IT IS A GOOD QUESTION. SOMETHING I WRESTLED WITH AS WE WERE PUTTING THIS TOGETHER NOT TO SAY BAY BASIC SCIENCE AND MECHANISTIC RESEARCH IS NOT IMPORTANT. CERTAIN QUESTIONS HAVE TO BE ASKED IN ISOLATION. AS LONG AS THE QUESTION IS BEING ASKED AND VISION FOR TRANSLATION IS CLEAR, I ALWAYS REFER TO MASTER THESIS PROJECT AS A PROJECT THAT HAS A DEAD END OR LESS LIKELY TO TRANSLATE TO THE NEXT LEVEL. ARE YOU LOOKING AT MAKING SURE THE MECHANISTIC QUESTION ACTUALLY HAS THE POTENTIAL TO TRANSLATE AND THEN I THINK THERE'S VALUE STILL. THEN YOU ARE ABLE TO EXPLAIN IT TO PEOPLE I WOULD THINK IN TERMS OF CONTEXT OF YOU MAY NOT SEE AN IMMEDIATE EFFECT ON YOUR HAND FUNCTION WITH THIS PARTICULAR STUDY THIS IS WHY UNDERSTANDING MOTOR FUNCTION OF THIS PARTICULAR MUSCLE THIS FINITE LEVEL IS GOING TO HOPEFULLY HELP UNDERSTAND HOW TO IMPROVE MOTOR FUNCTION ON LARGER SCALE DOWN IT'S A CHALLENGE. YOU NEED BASIC MECHANISTIC FOUNDATION FOR QUESTIONS IN ORDER TO BE ABLE TO THEN TRANSLATE THINGS MORE EFFECTIVELY DOWN THE ROAD. IF WE MISS THE MECHANISMS WE CAN BE OFF IN LEFT FIELD AND WAISTING TIME RESOURCE ASKING THE WRONG QUESTION. >> PUBLICIZING NEGATIVE DATA. IF YOU ARE NOT DOING SOMETHING THAT YOU DIDN'T INTEND TO THAT'S IMPORTANT FOR THE COMMITTEE TO KNOW. >> BUTBLY SIDINGS IT AND FOCUS GROUPS HAVE THE QUOTE OR EXPLANATIONS THAT YOU CAN GET VALUE OUT OF IT SO IT'S PUBLISHABLE. THERE'S STILL A HUGE BARRIER TO ACTUALLY BEING ABLE TO GET THESE MANUSCRIPTS PUBLISHED WHEN NEGATIVE TRIALS IN RESPECTABLE JOURNALS SO HOW DO YOU PACKAGE IT IN A WAY THAT'S STILL INFORMING THE NEXT CLINICAL STUDY SO ATTRACTIVE TO EDITOR EDITORIAL BOARD REVIEWERS. >> AS A COMMENT IT DOESN'T HAPPEN AS MUCH IN REHAB BUT FOR US IN PHARMA, RIGHT NOW STUDIES ARE BEING CONDUCTED IN ANTI-AMYLOID, MOST OF THOSE FAILED. WHAT GOES OUT IS IF YOU ARE DOING A STUDY TERMINATE THIS STUDY OFTEN TIMES YOU WANT PATIENTS TO COME BACK TO FINAL SCANS BECAUSE ULTIMATELY EVEN THOUGH THERE MIGHT BE A SAFETY PROBLEM, MIGHT BE A RISK BENEFIT YOU MIGHT SEE BENEFIT TO RECAST IT AS WHAT IS THE BEST PATIENT. THE PATIENTS DON'T COME IN BECAUSE THAT I BELIEVE THERE'S NO BENEFIT AT ALL FROM THEIR PARTICIPATION. THEY LOSE ALL THAT INFORMATION COMPLETELY. SO OFTEN TIMES IF YOU EVENTUALLY END UP SAY WITH MORE INVASIVE SPINAL CORD INJURY INTERVENTIONS, THERE'S A SEVERAL STUDIES TERMINATED, MAYBE YOU WOULD NOT GET THAT FINAL INFORMATION DON'T COMMUNICATE CAREFULLY, IT'S IMPORTANT FOR PATIENTS TO COME IN. >> IT'S IMPORTANT STRUCTURE SO YOU ALWAYS MAYBE WRAPPING UP SOMETHING BY WHAT YOU ARE EXPLAINING HOW IS THERE SOMETHING THAT YOU LEARN OUT OF THAT TO MAYBE GENERATE WAS THERE AN UNEXPECTED OUTCOME. >> PATIENT IS IMPORTANT CHOICE. STAY TERMINATE THROUGH THEIR MIND LET ME GET TO THE NEXT ONE BECAUSE THAT IS WHAT WILL HELP ME THE MOST. MOST PATIENTS ARE ALTRUISTIC. IF THEY JOIN STUDY IF THEY THINK THEIR BENEFIT THEY ARE WILLING TO MAKE ADDITIONAL SACRIFICE. IF THEY THINK IT'S USEFUL FOR THE RESEARCHERS WHY SHOULD THEY CONTINUE WHATSOEVER. >> YOU HAD A QUESTION? >> THE OTHER THING WE SOMETIMES OVERLOOK THINGS WE ALREADY HAVE AVAILABLE TO. SO PUBLISHED PAPERS ARE IMPORTANT AND LATE SUMMARIES TO PEOPLE WHO ARE PARTICIPATING ARE IMPORTANT BUT ALSO FOR RESEARCH COMMUNITY, I THINK CLINICALTRIALS.GOV IS ANOTHER REALLY IMPORTANT PORTAL TO USE. FOR NIH FUNDED STUDIES NON-NIH FUNDED STUDIES FOR ANY CLINICAL TRIAL REQUIREMENTS ARE CHANGING FOR THAT AND THE PLATFORM IS CHANGING. THEY ARE PROBABLY ALSO DOING REQUEST FOR INFORMATION, THEY ARE MEETING WITH MULTIPLE STAKEHOLDERS ON REDESIGN OF THAT PLATFORM. BUT RETURN OF RESULTS IS GOING TO BE A FEATURE. AS WELL AS LAY SUMMARIES AS WELL AS SUMMARY OF RESULTS. LET'S SAY YOU CAN'T GET IT PUBLISHED BECAUSE IT'S A NEGATIVE FINDING. IT AT LEAST WILL BE IN THAT PORTAL. WHICH I DO THINK HELPS IN TERMS OF WHAT YOU ARE TALKING ABOUT IN TERMS OF THE RETURN OF RESULTS WHEN YOU MAY NOT HAVE A PUBLICATION TO SHARE AND RETURN OF RESULTS MORE BROADLY TO THE AMERICAN PUBLIC AND THE INTERESTING THING THAT I'M LEARNING MORE ABOUT CLINICALTRIALS.GOV IS THEY ARE GOING THROUGH THIS PROCESS BUT THE BULK OF STUDIES IN THAT PORTAL ARE NOT NIH FUNDED. SO REALLY DOES REPRESENT THE PRIVATE THERE ARE VAGARIES IN THAT WHICH I FIND INTERESTING ESPECIALLY RELATES TO THERAPIES THAT ARE THROUGHOUT, MORE VETTING IN TERMS OF ACTUAL CLINICAL STUDY VERSUS A CLINICAL INVESTIGATION THAT IS REALLY AN AVAILABLE TREATMENT WITHOUT ANY SORT OF VALIDATION OF THAT. AID THINK THAT IS GOING TO IMPROVE AS WE GO BUT ENCOURAGE THIS COMMUNITY TO LOOK WHEN THEY PUT THAT OUT OBVIOUSLY INCLUDE IN OUR NEWS LETTER BUT COMING OUT WITH REQUEST FOR INFORMATION. ARE THERE PLACES THESE PERSPECTIVES WOULD BE USEFUL AND INFORMING WHAT IS IN THE RESULTS OF THAT PARTICULAR PORTAL? THAT'S A GREAT OPPORTUNITY TO HAVE A VOICE AND WHAT IS INCORPORATED AND WHEN THEY REVISE THE PLATFORM. IT'S GOING TO BE REALLY VALUABLE. >> IT'S GREAT TO SEE THE MOMENTUM THAT HAS COME FROM IN TERMS OF REPORTING, I MISSPOKE EARLIER WITH CLINICALTRIALS.GOV WHERE THE REPORTING RESULTS COME IN AND IT'S THE STANDARD NOW IF YOU WANT A PAPER PUBLISHED YOU BETTER BE REGISTERING IT IN CLINICALTRIALS.GOV FROM THE GET GO. SO THAT'S BECOME WIDELY KNOWN NOW WITH DECISIONS TO WHETHER OR NOT THEY CAN PUBLISH SOMETHING OR NOT THAT WAS OR WASN'T REGISTERED IN TIME BUT NOW IS NORM SO IT'S CHANGED AND WILL CONTINUE TO CHANGE PUBLIC ACCESS ABILITY TO SOME OF THOSE FINDINGS. >> GO TO SCITRIALS.ORG THAT IS SOMETHING WE CREATED FOR CONSUMERS. SO WE TOOK CLINICALTRIALS.GOV DATA AND MADE IT A LAYMAN'S SUMMARY OF IT AND FILTERED OUT STUDIES WE THOUGHT WERE NOT APPROPRIATE TO BE THEREON EITHER. -- THERE, EITHER. >> YES. >> THE YOU MENTIONED THE IMPORTANCE OF DISSEMINATION AND REPORTING OF STUDY RESULTS EVEN THE SETTING OF NEGATIVE STUDY. BUT I THINK WHETHER THE STUDY IS POSITIVE OR NEGATIVE, I THINK THERE'S CRITICAL VALUE IN THAT DATA. AND A NEED FOR SHARING OF DATA, FOR INSTANCE PLACEBO DATA IN A THERAPEUTIC TRIAL CAN BE SHARED WITH ADVOCACY COMMUNITIES AND ACADEMIC COMMUNITY AND THAT MASS BOW DATA CAN BE INCREDIBLY USEFUL FOR PLANNING FUTURE STUDIES FOR USING IT AS A BENCHMARK FOR OTHER DATA SETS TO PROVIDE VALIDATION OF HISTORICAL MALL HISTORY DATA VIS-A-VIS PLACEBO COLLECTED DATA. OF CLINICAL TRIALS, I'M SEEING A LOT OF SPONSORS NOW WHO ARE ACTUALLY VERY WILLING TO ACTUALLY SHARE THEIR DATA WITH PATIENT ADVOCACY GROUPS AND GET THE DATA INTO THE HANDS OF ADVOCACY COMMUNITY SO THAT THEN THE ADVOCACY COMMUNITY CAN PARTNER WITH ACADEMIC INVESTIGATORS TO REALLY MAKE USE OF THAT PLACEBO OR UNTREATED CONTROL DATA. >> GREAT TO HERE. THERE'S POSITIVE MOVEMENT IN THAT AREA. >> I FEEL LIKE IF YOU ARE GETTING ANY SORT OF FUNDING FOR YOUR PROJECT IT SHOULD BE RESULTS SHOULD BE PUBLICIZED, SOMETHING SIMPLE AS THE GETTING THE RESULTS WE EXPECTED OUT OF IT. BUT IT SHOULD BE MADE PUBLIC IN SOME FORMAT. >> WE HAVE A COUPLE OF SLIDES LEFT FOCUS ON HOW WE COULD -- HOW WE CAN ENCOURAGE MORE OPPORTUNITIES FOR ENGAGEMENT AND WE HAVE MORE TIME FOR DISCUSSION FOR THIS DIALOGUE. ONE THING HERE IS SOMETHING TO CONSIDER, COULD THERE BE MORE MECHANISMS THROUGH GRANT REVIEW PROCESSES WHERE WE TRACK INCLUSION OF DIVERSE IN TERMS OF DESIGN IMPLEMENTATION, PART OF SOME GRANT PROCESSES ALREADY BUT COULD IT BE MORE FORMAL LIEU THE NIH SYSTEM IN SOME WAY SHAPE OR FORM. WE CERTAINLY LOOK AT AWE DRESSING DIVERSE RECRUITMENT IN TERMS OF TABLES WE REPORT ON ETHNIC AND RACIAL COMPOSITION OF INTENDED PARTICIPANTS. BUT COULD THERE BE MORE, COULD THERE BE A SECTION LIKE WOMEN AND CHILDREN THAT SPEAKS MORE TO DISABILITIES AN THINGS WE TALK ABOUT NOT JUST NECESSARILY RACIAL ETHNIC CONSIDERATIONS OR PERCENTAGE OF WOMEN AN CHILDREN REPRESENTED. BUT A LITTLE BROADER IN TERMS OF EXPLAINING PLAN FOR MAXIMIZING INCLUSION ACROSS THE BOARD. SO ONE POSSIBILITY TO CONSIDER, THEN AS FAR AS EXAMPLES OF THINGS AVAILABLE IN TERMS OF PROMOTING DIVERSITY OF APPLICANTS AND AWARDEES IN THIS CASE, THERE ARE SOME K AWARDS THERESA CRUZ WAS KIND TO FIND AND HIGHLIGHT THESE. MANY IN THE AUDIENCE KNOW MORE THAN SPECIFICS ABOUT THE MECHANISMS K AWARD PROMOTING DIVERSITY IN NEUROSCIENCE RESEARCH THROUGH NINDS. ONE POTENTIAL MECHANISM AND THEN THERE'S A K-9 9 R 00 THROUGH A BRAIN INITIATIVE THAT PROMOTES DIVERSITY, DURING CAREER TRANSITIONS. THERE ARE SOME STARTING TO EMERGE, PROBABLY COULD BE MORE OF THESE IF THIS IS REALLY A POINT OF EMPHASIS IN OUR RESEARCH COMMUNITY. TO ENHANCETY VERSETY AND REPRESENTATION ACROSS THE BOARD. THEN THERE ARE SOME ADMINISTRATIVE SUPPLEMENTS THAT ARE AVAILABLE TO INDIVIDUALS WHO ARE OR BECOME DISABLED OR NEED ADDITIONAL SUPPORT TO ACCOMMODATE DISABILITY. SO THERE ARE SOME MECHANISMS AVAILABLE ALREADY IN ORDER TO PROMOTE MORE INCLUSION. AND SUPPORT DIVERSITY. BUT CERTAINLY THERE ARE LIMITED IN NUMBERS IN TERMS OF NUMBER OF MECHANISMS AND OPPORTUNITIES AND COULD PROBABLY GROW FURTHER DOWN THE ROAD. I WILL LET ROB WRAP UP HERE AND OPEN THE FLOOR TO MORE DISCUSSION. >> OBVIOUSLY WE GAVE GOOD IDEAS FOR PATIENT ENGAGEMENT. OVERALL TOO, WHEN YOU BRING SOMEBODY INTO YOUR LAB, ENCOURAGE THEM TO BE MORE ENGAGED MAYBE NETWORK WITH ONE OF YOUR PEERS TO HELP THEM UNDERSTAND WHAT YOU ARE DOING MORE GET THEM TO SPEAK YOUR LANGUAGE. FROM CONSUMERS ARE OUT THERE FOR PATIENTS, PARTICIPANTS, I ENCOURAGE YOU TO REACH OUT TO RESEARCHERS THAT YOU MIGHT WANT TO CHATTED WITH. AND GO DO LAB TOUR AND MEETING AND TALK ABOUT WHAT NEEDS YOU WANTED. IT'S BEEN A REWARDING EXPERIENCE >> WE HAVE A COUPLE OF ACKNOWLEDGMENTS. CYNTHIA WHO PUT TOGETHER THE SLIDES AND KATIE WHO I MENTION IN THE STAKEHOLDER ENGAGEMENT VETERAN TEAM. AND ROB YOU HAVE -- >> HEATHER GAINFORD AND JOHN FROM PRACTICES. THERE'S NORTH AMERICAN SPINAL CORD INJURY CONSORTIUM AND SOME OF THE GROUPS DEVELOPING A TOOL KIT FOR PATIENT ENGAGEMENT. IT'S BEEN COME OUT IN A WEEK OR TWO, IF NOT A MONTH OR TWO. T BUT IT IS UNFORTUNATE THAT THIS WAS A LITTLE BIT TOO EARLY TO SHARE THOSE FINDINGS. THEY HAVE BEEN P DONE STUDIES ON THAT. AND ON THIS. >> WE THOUGHT WE WOULD OPEN THE FLOOR WITH THE REMAINDER OF TIME TO DISCUSSION TO OTHER IDEAS WE HAVEN'T MENTIONED, THINGS YOU HAVE FOUND SUCCESSFUL IN TERMS OF ENGAGING STAKEHOLDERS OR OTHERD WHERES OR THOUGHTS WE HAVE HEARD HELPFUL PERSPECTIVES. BUT OTHER RECOMMENDATIONS TO SHARE WITH GROUP IN TERMS OF SUCCESS IN THIS PARTICULAR AREA OR CHALLENGES. >> I WANT TO ASK FOR RECOMMENDATION, I GUESS ROB, I HAVE BEEN IN SOME DOD PANELS WHERE WE HAD I COMPLETELY AGREE PATIENT ENGAGEMENT, WHAT ARE YOUR SUGGESTIONS FOR VETTING PATIENTS? YOU KNOW RESEARCH, YOU THOUGHT ABOUT THIS QUITE A BIT. SOMETIMES INDIVIDUALS DON'T UNDERSTAND RESEARCH AND THEY ARE NOT THINKING LIKE IT THE WAY RESEARCHERS ARE AND IT'S HARD TO MAYBE GET MOST APPROPRIATE PERSPECTIVE SO WHAT IS THE BEST WAY TO VET PATIENTS? >> AS FAR AS LIKE -- >> EXPERTISE. FOR RESEARCH. >> I THINK THAT CAN BE TRIAL AND ERROR. >> ALL THE OTHER REVIEWERS ARE VETTED, RIGHT? >> YEAH. AND OBVIOUSLY THERE'S A PRETTY GOOD NETWORK WITH THE CDMRP PROGRAMS. TRYING TO TAP INTO THAT I THINK IS A GOOD START. THEY ARE NOT ALWAYS CONSUMERS CLOSE TO YOU. >> ALSO THERE'S A NETWORK OF PRETTY -- I THINK A CONSUMER REPRESENTATIVE ORGANIZATION LIKE LOCAL, IF YOU HAVE A DISEASE COMMUNITY BIG ENOUGH COMMUNITY, YOU FIND THAT FROM HOPEFULLY THERE'S FEW PEOPLE LIVING WITH THE DISEASE CONDITION REACHING OUT TO. I THINK THOSE PEOPLE ARE PRETTY GOOD ADVOCATES WAS THEY ARE -- >> HAVE YOU BEEN A PROCESS WHERE MAYBE INVESTIGATORS ABOUT RACKET BASIC METHODS ASK WHAT YOUR THOUGHTS ARE AND BASED ON WHAT YOUR RESPONSE IS, THEY CAN DECIDE WHETHER OR NOT YOU -- I SEE SOMETIMES THEY DERAILED THE CONVERSATION BUT INTERESTED IN THIS BUT RESEARCH IS WAY OVER -- >> ABSTRACT RESEARCH PLAN ARE GOOD STARTS. BUT EVEN BEFORE THAT, BRINGING THEM IN WHEN YOU HAVE A MEETING WHERE YOU ARE DEVELOPING SPECIFIC AIMS. WE WANT TO STUDIED THIS THIS IS WHAT I'M THINKING, WHAT ARE YOU THINKING ABOUT THIS. >> I THINK THE STAKEHOLDER VETERANS BOARD WE MENTIONED THE INTERVIEW WE SIT DOWN WITH THEM ONE ON ONE FOR 20, 30 MINUTES AND EXPLAIN WHAT THEY ARE GOING TO BE INVOLVED IN AND HOW AND ASK QUESTIONS AND YOU CAN GAUGE WHETHER OR NOT SOMEBODY IS GOING -- WHETHER THEY HAVE ANOTHER AGENDA THAT WILL DERAIL SOME OF THE DISCUSSION OR OPEN TO THE WAY THE FORMAT IS STRUCTURED AND ANSWERED QUESTIONS WITH TRIAL AND ERROR, BUT I THINK BRINGING THEM IN BEFOREHAND AND MAKING SURE THEY UNDERSTAND THE PARAMETERS AND GROUND RULES HELPFUL AND YOU CAN GET A GOOD SENSE EARLY ON MAKING SURE -- >> MAKING SURE THEY UNDERSTAND THE STRUCTURE HOW YOU ARE OPERATING. HOW HEADACHE WORK WITH THAT'S SPECIALLY DEVELOPING A CLINICAL PROTOCOL FOR A TRIAL, SOMEWHERING THEM REVIEW THAT PROCEDURE, DOING A DRY RUN THROUGH IT. YOU CAN FIGURE OUT THE TIME IT TAKES TO PERFORM IN CLINIC. >> WHAT YOU SAID EARLIER GETTING THEM INVOLVED EARLIER, RALPH MENTIONED THAT YOU AS A PROGRAM OFFICER YOU GET A CALL AND IT IS A WEEK BEFORE THE GRANTS IS DUE AND YOUR SUGGESTIONS HOW TO COMPLETELY REVAMP EVERYTHING ARE NOT ALWAYS WELL RECEIVED WHEN YOU ARE THAT FAR INTO IT. SO MAKING SURE SAME THING IF YOU HAVE THEM COME IN THE FINAL STAGE WHEN READY TO SEND GRANT OUT AND SAY I NEED YOUR NOD OF APPROVAL YOU WON'T GET EFFECTIVE EXCHANGE AND INTERACTION IF YOU ARRANGED IT FROM THE GET GO. >> I HOPE YOU DON'T START WRITING A GRANT A WEEK BEFORE THE DEADLINE. >> I DON'T THINK ANYONE STARTS A WEEK BEFORE DEADLINE BUT OVERHAULING IT, RIGHT? OTHER QUESTIONS OR THOUGHTS? YES. >> THANK YOU FOR THAT NICE PRESENTATION. I THINK ROB, I APPRECIATED YOUR SLIDE ABOUT THAT TOKENISM AND HOW SOMETIMES PEOPLE GET INVITED ESPECIALLY CONSUMER PARTICIPANTS AS WELL AS -- AND THEY DON'T GET -- REALLY IMPORTANT. FOR THOSE OF US WHO WORK WITH VERY YOUNG INFANTS, IT IS -- THIS IS SOMETHING THAT WE LEARNED VERY EARLY THAT WE COULDN'T DO WITHOUT -- WE COULDN'T DO WITHOUT THAT PARTNERSHIP EARLY IN THE PROCESS. EVEN LOOKING AT HOW ACE LETTIC THE THING IS THAT YOU ARE GOING TO BE USING FOR THEIR VERY YOUNG INFANTS AND GETTING FEEDBACK FROM THE CONSUMERS. I WOULD LIKE TO GO TO THE END, THE RECOMMENDATION SLIDE THAT JENNIFER YOU SHOWED REGARDING THE REVIEWERS STARTING TO APPRECIATE SOMEHOW MAYBE GIVE SOME POINTS TOWARDS FOR PROPOSALS THAT HAVE INCORPORATED THE LAST SLIDE RECOMMENDATIONS THAT YOU HAD. INVESTIGATORS FOR INCLUSION OF THAT. /THINK THAT'S SO IMPORTANT BECAUSE IT DOESN'T HAVE TO BE A SECTION ON ITS OWN. T I STILL REMEMBER WHEN WE WERE TRAYING AS REVIEWERS WE WERE BEING TRAINED TO LOOK AT RIGOR AND REPRODUCIBILITY. EVERY TIME IT GOT REPEATED REPEATED REPEATED AND EVENTUALLY BECAME SOMETHING THAT I THINK REVIEWERS STARTED TO LOOK AT. AND I'M THINKING THIS IS SOMETHING THAT IF IT INCLUDED IN THE TRAINING OF REVIEWERS TO SAY BECAUSE IT IS REALLY PART OF RIGOR. BECAUSE IT'S RELEVANT TO THE PEOPLE. SO IF MAYBE THEY EXPAND THIS INFORMATION ABOUT THE RIGOR AND REPRODUCIBILITY TO INCLUDE REPRESENTATION I THINK MAYBE A STEP THAT WILL HELP INCLUDE ENCOURAGE PEOPLE BEING INCLUDED. >> THAT'S CERTAINLY MORE AN NIH LEVEL CHANGE -- THAT WOULD BE TO GOAL TO HAVE THAT, ONE OF THOSE SUBHEADERS IN TERMS OF WHAT WE ARE LOOKING FOR. >> COUPLE OF COMMENTS. PCORI HAS DONE A GOOD JOB OF THIS. WHEN THEY STARTED THE APPLICATIONS THEY WERE GETTING DIDN'T UNDERSTAND HOW TO DO THIS. BUT NOW WE ARE SEEING AT THAT MEETING HOW WELL MANY STUDIES ARE REALLY ENGAGING PEOPLE THE WAY YOU DESCRIBED. THERE ARE ALSO A LOT OF TOOLS ON LINE ABOUT COMMUNITY ENGAGED RESEARCH AND COMMUNITY CDPR THAT WOULD BE HELPFUL. ONE OF THE THINGS IN THE STUDY, ONE PCORI STUDY I WAS ON WE STRUGGLED WITH WAS AT THE END OF THE STUDY SO YOU HAVE A GROUP WHO HELPED YOU DESIGN THIS WHOLE STUDY FROM THE START. AND THEY HAVE BEEN WITH YOU FOR FOUR OR FIVE YEARS. NOW STUDY IS OVER AND YOU DON'T HAVE ADDITIONAL FUNDING. PEOPLE ARE GOING ON TO THE RESEARCH TEAM IS GOING ON TO DIFFERENCE THINGS. FIGURING OUT A WAY TO MAKE -- BECAUSE THESE PATIENT AT LEAST IN OUR CASE PATIENT AND CAREGIVER PARTNERS BECAME REALLY INVESTED IN THIS WORK AND INVEST IN THE RELATIONSHIPS WITH US AS CLINICIANS AND RESEARCHERS AND SO WE WERE ABLE TO DO IT BUT YOU REALLY HAVE TO THINK ABOUT THAT. IF THERE IS A POINT OF DISENGAGEMENT HOW DO YOU DO THAT IN A WAY THAT IS CARING AND YOU ARE NOT CUTTING PEOPLE OFF? THAT WAS -- WE REALLY HAD TO THINK ABOUT THAT WITH THIS ONE PARTICULAR STUDY I WAS ON. BECAUSE OF THE WAY PEOPLE WERE ENGAGED WITH US. >> HOW DID YOU END UP RESOLVING OR PURSUING THAT? >> WE STARTED TALKING ABOUT IT EARLY ON. COMMUNITY ADVISORY BOARD MEETINGS QUARTERLY AND THEY WERE AT THESE MEETINGS AND WE TALKED ABOUT THE FACT THAT THERE WAS GOING TO COME TO A POINT OUR LEAD PI WAS A PHYSICIAN. THESE WERE PATIENTS AND CAREGIVERS. SHE TIN ADVISE THEM BUT THERE IS -- PEOPLE REALLY REVERED HER AS THIS WONDERFUL CARING PHYSICIAN. SO SHE KEPT SOME EMAIL CONTACT WITH THEM AT THE END OF THE STUDY AND WE DID INCLUDE THEM IN THEY DID COME TO PCORI MEETINGS WITH US FOLKS INTERESTED AND IT WAS EASY FOR SOME, I WAS THINKING OF TWO IN PARTICULAR THAT IT WAS A REAL STRUGGLE FOR. SO WE TALKED IT THROUGH BUT IT WAS NOT EASY, IT WASN'T EASY FOR US EITHER. THAT WAS A REALLY HARD TRANSITION TO MAKE FOR PEOPLE ON SOME OF US IN THE ROOM AROUND THAT. YOU HAVE TO THINK ABOUT THAT AND THINK ABOUT HOW YOU ARE GOING TO FRAME THAT WHEN PEOPLE COME ON TO YOUR STUDY. >> FROM A CONSUMER PERSPECTIVE, YOU GET PASSIONATE ABOUT THAT EFFORT. THEY WERE WORKING ON OR HELPING WITH. IT IS IMPORTANT CONSULTANT YOU NEED CONSULTANT TO MAKE SURE HAY UNDERSTAND THAT CONSULTANT ROLE FROM A PATIENT ADVISOR TO PARTICIPANT IN THE CLINICAL STUDY YOU ARE BRINGING THEM IN FOR THEIR EXPERTISE AND LIVING WITH THE DISEASE CONDITION. THERE'S I THINK CONSULTANTS UNDERSTAND THEIR ROLE AND THEY ARE ASKED TO JOIN SOMETHING AND I THINK IT ALSO THERE IS MUTUAL RESPECT, YOU ARE BRINGING EXPERT OPINION ON THEIR SPECIFIC INTELLIGENCE ON THAT MATTER. >> COULD YOU CHANNEL THOSE ENERGIES HELPING DISSYSTEMNATE INFORMATION? GETTING OUT THERE AND SPREADING -- >> WE DID THAT. WE HAD ONE OF OUR PARTICIPANTS DID A VIDEO FOR PCORI THEY REVIEWED ALL OF OUR MANUSCRIPTS. SO WE DID KEEP THEM ENGAGED IN THAT WAY THOUGH WE WEREN'T HAVING THE COMMUNITY ADVISORY BOARD MEETINGS ANY MORE, WE KEPT THOSE THAT WANTED TO STAY ENGAGED WE KEPT ENGAGED THAT WAY. BUT THERE COMES A POINT WHERE SO IT WAS A TRENDING DOWN OF ENGAGEMENT. AND THEY KNEW, THEY KNEW WE WERE GOING TO DO THAT. THESE BECOME PEOPLE YOU KNOW ABOUT THEIR PERSONAL LIVES, MAY HAVE BEEN WITH YOU A LONG TIME. IT IS NOT SOMETHING I THINK ANY OF US THOUGHT ABOUT BUT NOT THE IMPACT IT WOULD HAVE ON BOTH SIDES I THINK. >> GOOD PERSPECTIVE TO THINK ABOUT THE STUDY UP AND RUNNING. AND THEN ANTICIPATING THAT TRANSITION DOWN THE ROAD. >> GENERATE RELATIONSHIPS. >> THAT WINDING DOWN IS A GREAT POINT TO END OUR DISCUSSION. THANK YOU BOTH SO MUCH. THAT WAS A WONDERFUL PRESENTATION. AND GREAT DISCUSSION. [APPLAUSE] >> I JUST WANT TO FINISH. I HAVE EIGHT YEARS OF LIVING WITH THIS INJURY. NA IS EIGHT YEARS OF EXPERIENCE AND KNOWLEDGE ABOUT MY CONDITION. AND IS THERE IS OVER 180,000 PEOPLE WITH SPINAL CORD INJURIES, ANYWHERE FROM ONE MINUTE TO OVER 50 YEARS LIVING WITH THIS SPINAL CORD INJURY. AND THAT'S A LOT OF YEARS OF EXPERIENCE OUT THERE FOR THIS ONE SPECIFIC DISEASE CONDITION. THERE'S A LOT OF EXPERIENCE OUT THERE THAT IS UNTAPPED. >> 20 MINUTES AFTER SO WE WILL COME BACK AT 35 AFTER. >> IT IS A PLEASURE TO INTRODUCE OUR BOARD MEMBER, DR. CRAIG MCDONALD WHO WILL BE TALKING ABOUT PRECISION MEDICINE IN PEDIATRIC REHABILITATION. OPTIMIZING THE FUNCTIONAL POTENTIAL OF EACH CHILD. Q. THANK YOU VERY MUCH. IS IT IS A PLEASURE TO BE ABLE TO SHARE SOME EXPERIENCES OF THE INTERFACE BETWEEN PRECISION MEDICINE AND PEDIATRIC REHABILITATION RESEARCH. I WILL SHARE SOME EXAMPLES OF HOW REHABILITATION RESEARCHERS HAVE BEEN ABLE TO CONTRIBUTE TO TEAM SCIENCE TO ENHANCE THE THERAPEUTIC DEVELOPMENT TO IMPROVE FUNCTIONAL CAPACITY OF CHILDREN WITH DISABLING CONDITIONS. AS A MATTERS OF DISCLOSURE OVER THE YEARS I HAVE BEEN CONSULTING WORK FOR A NUMBER OF PHARMACEUTICAL COMPANIES IN THE DUCHENNE MUSCULAR DYSTROPHY DISCLOSURES RELATED TO SPINAL MUSCULAR ATROPHY. I WOULD LIKE TO START WITH A CONSTRUCT A LIFE SPAN PERSPECTIVE WHEN TRYING TO MAINTAIN THE HIGHEST LEVEL OF HEALTH AND FUNCTION IN PROGRESSIVE PHYSICAL DISABILITIES. MANY DISABLING CONDITIONS TEND TO BE FAIRLY STATIC THIS MORNING WE WILL FOCUS ON PROGRESSIVE PHYSICAL DISABILITIES. OBVIOUSLY IF YOU LOOK AT THE MAXIMAL HEALTH AND FUNCTIONING THERE IS A NATURAL AGING THAT OCCURS WITH DISEASE BUT THERE'S EARLY GROWTH AND DEVELOPMENT THAT IS REALLY A HALLMARK OF PEDIATRIC REHABILITATION RESEARCH, THIS PERIOD OFFER GROWTH IN MATURATION AND DEVELOPMENT THAT'S SUPER IMPOSED UPON PERHAPS A PROGRESSIVE DISABLING CONDITION. WITH ADULT PROGRESSIVE DISABLING CONDITIONS YOU CAN HAVE EARLY INTERVENTION THAT MIGHTS IMPROVE OUTCOMES ALLOW PEOPLE TO STAY ABOVE DISABILITY THRESHOLD PERHAPS LATE INTERVENTIONS THAT HAVE LESS EFFECT AND NO INTERVENTIONS WHERE THERE'S EARLIER PROGRESSION AND FUNCTIONAL DETERIORATION. THIS MORNING WE WILL FOCUS ON CHILDHOOD ONSET PROGRESSIVE DISEASE SPECIFICALLY TWO EXAMPLES OF CHILDHOOD ONSET RAPIDLY PROGRESSIVE DISEASES. THEN WE ARE GOING TO ALSO BE FOCUSING ON THE SWEAR FACE OF REHABILITATION RESEARCH WITH PRECISION MEDICINE WHICH IS AN EMERGING APPROACH FOR DISEASE PREVENTION AND TREATMENT THAT TAKES INTO ACCOUNT PEOPLE'S INDIVIDUAL VARIATIONS IN GENES ENVIRONMENT AND LIFESTYLE AND REALLY THE TWO EXAMPLES I GIVE HERE ARE REALLY EMERGING TRIUMPHS IN PRECISION MEDICINE RELATED TO TREATING DISABLING CHILDHOOD CONDITIONS. THE TWO EXAMPLES DOES CHEN MUSCULAR DYSTROPHY AND SPINAL MUSCULAR ATROPHY, IT IS A RARE DISORDER AFFECTING BOYS AND YOUNG MEN, THIS IS RELENTLSSLY PROGRESSIVE PATIENTS LOSE MOTOR SKILLS, EVENTUALLY LOSING AMBULATION AND UPPER LIMB FUNCTION, THEY EVENTUALLY DEVELOP PROGRESSIVE PARALYSIS RESPIRATORY FAILURE, CARDIO CARDIOMYOPATHY AND PREMATURE DEATH. THE CONSEQUENCES ARE DUE TO A SINGLE GENE DEFECT THAT CAUSES ABSENCE OF DISTROPIN PROTEIN SO REDUCED ABSENCE DYSTROPHIN PROTEIN CAUSES A MECHANICALLY WEAKENED MUSCLE MEMBRANE PRONE TO CONTRACTION INJURY FOCAL TEAR DURING ACTIVITY THAT CAUSES MASSIVE INFLUX OF EXTRA CELLULAR CALCIUM INTO THE INSIDE MUSCLE FIBER PROTEOLYTIC ENZYMES AND SEGMENTAL NECROSIS OF MUSCLE CELL. SO YOU GET A PRIMARY GENE ABNORMALITY CAUSES ABSENCE OF PROTEIN, MUSCLE MEMBRANE SUSCEPTIBLE TO INJURY, CASCADE OF EVENTS LEADING TO MULLS FIBER INJURY AND DEGRADATION. THE MUSCLE FIBERS UNDERGO DEGENERATION REGENERATION WITH SATELLITE CELL ACTIVATION AND EVENTUALLY MUSCLE CELLS DIES AND NEEDS TO BE REPLACED BY FAT AND CONNECTIVE TISSUE. HERE IS SOME EXAMPLE MUSCLE BIOPSIES FROM CHILDREN AND YOUNG ADULTS WITH DUCHENNE MUSCULAR DYSTROPHY YOU SEE PROGRESSIVE INFILTRATION AND REPLACEMENT OF MUSCLE FIBERS BY FAT AND SCAR TISSUE CONNECTED TISSUE, THE HISTOLOGY ON THE FAR RIGHT IS A POSTMORTEM VIEW IN 19-YEAR-OLD YOU CAN SEE THERE A MUCH MUST -- THERE IS NOT MUCH MUSCLE FIBER LEFT. THE LOWER IMAGE IS THE ELBOW YOU CAN SEE THE YELLOW APPEARANCE THE BICEPS MUSCLE AND THIS IS LITERALLY A PICTURE OF THAT PATIENT GASTRIC MUSCLE POSTMORTEM. SO WITH REGARD TO THE PATHOMECHANISM OF DISEASE, MEMBRANE INSTABILITY MUSCLE FINER NECROSIS, ACTIVATION OF THE NF KAPPA B PATHWAY AND INFLAMMATION AND EVENTUALLY THE MUSCLE FIBER UNDERGOES FIBROSIS, THERE'S SATELLITE CELLK AVATION AND MUSCLE FIBER REGENERATION THAT OCCURS PRIOR TO IRREVERSIBLE FIBER DEATH. I SHOULD COMMENT IN H EARLIES THE OF REHABILITATION AND MEDICAL MANAGEMENT OF THESE PATIENTS, THERE'S CRITICAL CARE STANDARDS IMPROVED YOU OUT COMES TREATMENT WITH GLEE CO-CORTICOIDS MANAGEMENT OF SPINE DEFORMITY, MECHANIC A.M. CAUCUSES, DEVICES NON-INVASIVE VENTILATION, CARDIAC MANAGEMET WITH MEDICATION, THAT CAN PROTECT THE HEART, RECOGNITION TREATMENT OF EARLY HEART FAILURE AND WHAT'S REALLY BEEN EMERGING THESE NOVEL DISEASE MODIFYING THERAPIES WHICH ARE VERY EXCITING. THERE'S IMPROVED OUTCOMES OVER THE LAST DECADES ON THE LEFT IS SURVIVAL CURVE AND SUCCESS OF DECADES SHOWING IMPROVED SURVIVAL IN DUCHENNE MUSCULAR DYSTROPHY PATIENTS, THE DATA ON THE RIGHT SHOWS IMPROVE SURVIVAL BY APPLICATION OF SPINAL SURGERY AND KNOCK NIGHTTIME NON-INVASIVE VENTILATION SIMILAR TO WHAT IS USED WITH CPAP DEVICE WITH OBSTRUCTIVE SLEEP APNEA, IN TENS OF MILLIONS OF AMERICANS. THEN DUCHENNE SURVIVAL REALLY IN A NUMBER OF STUDIES HAS REALLY BEEN SHOWN TO BE IMPACTED PRIMARILY BY THE USE OF NON-INVASIVE VENTILATION, NIGHTTIME THIS IS SURVIVAL CURVE IN THE YELLOW SHOWING SURVIVAL IN PATIENTS THAT CHOOSE TO BE VENTILATED NIGHTTIME VERSUS THOSE NOT VENTILATED. THERE'S A TEN YEAR PROLONGATION OF SURVIVAL IN PATIENTS THAT ARE VENTILATED. THEN WITH THE STANDARD OF CARE STEROID TREATMENT SURVIVAL CURVE ON THE LEFT SHOWING SURVIVAL WITH STEROIDS VERSUS SURVIVAL WITHOUTSER ROADS, THEN ON THE RIGHT, CARDIAC MANAGEMENT WITH USE OF CARDIAC MEDICATION ACE INHIBITORS TO REDUCE THE HEART AND UP LOAD STRESS ON THE HEART SHOWING IMPROVED SURVIVAL WITH LOAD REACTION. THIS IS FROM THE DUCHENNE CARE CONSIDERATION, THE CDC SPONSOED THIS ACTIVITY, THESE WERE PUBLISH IN 2010. AGAIN REVISED VERSION IN 2018, THE NUMBER OF DISCIPLINES THAT ARE INVOLVED IN THE TREATMENT OF PATIENTS WITH DUE SHEN MUSCULAR DYSTROPHY IS REALLY A SIGNIFICANT. SO OBVIOUSLY THE NEEDTOR TEAM SCIENCE TO REALLY INTERFACE WITH THIS COMPREHENSIVE DUCHENNE CARE TEAM. THERE ARE STAGES OF DUCHENNE MUSCULAR DYSTROPHY CAPTURED WITH A VARIETY OF POLITICAL END POINTS HERE SHOWN ON THE RIGHT. THE BAILEY SCALES OF INFANT DEVELOPMENT, FREE ASSESSMENT TIME FUNCTION TEST, SIX MINUTE WALK TEST, THERE ARE EMERGING TESTS OF UPPER LIMB FUNCTION BUT WHAT WE HAVE IS A STEREOTYPIC PATTERN PROGRESSIVE PATIENTS PASSED THROUGH PAGES WITH DELAYED IMPAIRED ACQUISITION OF MILD STONES AND MOTOR SKILLS AND EARLY AMBULATORY STAGE MODEST FUNCTIONAL DECLINE, LATE AMBULATORY STAGE MORE RAPID FUNCTIONAL DECLINE AND EARLY NON-AMBULATORY STAGE EWE HAD OVERHEAD REACH AND HAND AND MOUTH FUNCTION AND EVENTUALLY LATE NON-AMBULATORY STAGE WITH HAND FUNCTION, AND ALSO PULMONARY FUNCTION AND REQUIRED NON-INVASIVE VENTILATION AND PERHAPS DAYTIME VENTILATION. JUST TO START HERE BY LOOKING AT THIS FIRST STAGE OF DELAYED OR IMPAIRED ACQUISITION OF MILESTONES, AND MOTOR SKILLS AND SOME OF THE ASSESSMENTS THAT HAVE BEEN EMPLOYED, THIS IS A CHILD FIRST ONE OF THE FIRST SIGNS OF MANY -- MOTOR WEAKNESS IS LIMITED CROSS SECAL AREA OF FLEXOR MUSCLE MASS SO THIS CHILD CAN'T BRING THEIR HEAD TO THE CHEST AGAINST GRAVITY. HERE IS A STEROID TREATED CHILD WITH DUE -- DUCHENNE, NORTH STAR HERE ON THE LEFT MOST DUCHENNE PATIENTS NEVER DEVELOP ABILITY TO HOP AND HE'S BEEN TREATED WITH STEROIDS AT YOUNG AGE AND IF HE'S ABLE TO HOP ON EITHER LEG. HE'S ABLE TO JUMP MOST PATIENTS DON'T DEVELOP THE ABILITY TO JUMP UNLESS THEY HAVE BEEN TREATED WITH STEROIDS. AND THEN WE ACTUALLY WILL TIME THE RISE FROM THE FLOOR, THIS IS ACTUALLY IMPAIRED T A VERY YOUNG AGE. THISES THE SO CALLED -- YOU CAN SEE HIS SISTER ENCOURAGING HIM TO STAND UP AREAS TRANSITIONING FROM BEFORE THAT, PUSH OFF THE KNEE DUE TO PELVIC GIRDLE WEAKNESS OF THE HIP EXTENSORS. THEN THE ABILITY TO RUN MOST DUCHENNE PATIENTS CAN'T RUN WITH BOTH FEET OFF THE GROUND PATIENT TREATED WITH STEROIDS IS ABLE TO RUN GETTING BOTH FEET OFF THE GROUND. THEN WE MOVE TO EARLY AMBULATORY STAGES WHERE THERE'S MORE PREDICTABLE MODEST FUNCTIONAL DECLINE AND LATE AMBULATORY STAGES OF THE DISEASE, HERE IS AN EXAMPLE, AGAIN OF A SUPINE MANEUVER SHOWING THE GAY ROWS MANEUVER, HERE HE GOES INTO TO A TRIPOD POSITION AND PUSH OFF THE KNEE BECAUSE OF HIP EXTENSOR WEAKNESS TO GET TO STANDING POSITION. HERE IS A CLASSIC MYOPATHIC GATE PATTERN. HE SWAYS TO THE SIDE, HE HAS LUMBARDOSIS, DIMINISHED CLASSIC MYOPATHIC GATE PATTERN. THIS PATIENT IS DOING THE TECH METER WALK RUN TEST. ABLE TO DO IT IN 6.5 SECONDS. YOU CAN SEE LEVEL OF FATIGUE AND DEGREE OF HIM BEING DEMONSTRATING A FATIGUE AND BEING TIRED JUST IN A SHORT DISTANCE. HERE IS THE NORTH STAR AMBULATORY ASSESSMENT WE DO A VARIETY OF MEASURES, CLINICAL MEASURES WHICH ARE RATED PHYSICAL THERAPISTS DEVELOPED THIS TECHNIQUE. THERE IS THE GARROW SIGN PATIENT UNABLE TO STAND WITHOUT USE OF UP PER EXTREMITIES. HE IS UNABLE TO JUMP, UNABLE TO HOP, UNILATERALLY ON ONE LEG. THESE ARE COMPONENTS OF THE NORTH STAR AMBULATORY ASSESSMENT DEVELOPED BY RESEARCH PHYSIOTHERAPISTS IN THE FIELD DEVELOPING THIS DUCHENNE SPECIFIC MEASURE OF DISEASE PROGRESSION. THIS IS A STAIR CLIMBING MANEUVER. THEN MOVING TO THE NON-AMBULATORY STAGES WHERE WE HAVE IMPAIRED UPPER LIMB STRENGTH AND ULTIMATELY A NEED FOR MECHANICAL VENTILATION, THIS IS THE SAME PATIENT EARLIER SEEN RUNNING AT AGE 17, THIS IS FILM IN THE HOME ENVIRONMENT WITH PERMISSION OF THE FAMILY. BUT YOU CAN SEE THIS TRANSFER OF THE FATHER HAVING TO EXERT A DEAD WEIGHT TRANSFER TO GET HIM TO HIS POWER WHEELCHAIR AND THEN BACK INTO BED. YOU CAN SEE THE INCREDIBLE BURDEN OF DISEASE ON THE PATIENT AND THE FAMILY MEMBER AS THIS DISEASE PROGRESSES OVER TIME IN THE LOWER EXTREMITY CONTRACTURES SEEN AT HIP KNEE AND ANKLE. HERE IS THE FATHER SETTING HIM UP WITH NON-INVASIVE NOCTURNAL VENTILATION SYSTEM USED AT NIGHTTIME IN THIS YOUNG MAN. THERE ARE EXCITING POTENTIAL FOR COMBINATION TREATMENTS IN DUCHENNE DYSTROPHY EMERGING, THE FIRST AND FOREMOST THAT HAS BEEN EMPHASIZED IS REPLACEMENT OF THE DYSTROPHIN PROTEIN. APPROACHES TO ACTUALLY DECREASE INFLAMMATION FIBROSIS, INCREASING MUSCLE MASS AND REGENERATION, BLOOD FLOW REGULATION ISSUES PERTURBATION IN CALCIUM HANDLING MITOCHONDRIAL DYSFUNCTION. WHAT WE ARE MOVING TOWARD IS POTENTIAL FOR COMBINATION TREATMENT. THERE ARE A NUMBER OF ACTIVE AGENTS THAT ARE ACTUALLY FDA APPROVED OR CURRENT TRIALS FOCUSING ON INFLAMMATION AND NF KAPPA B WHICH IS CHRONICALLY ACTIVATE IN DOES CHEN, PREDNISONE APPROVED SPECIFICALLY FOR DUCHENNE. THERE ARE ACTUAL DESIGNER STEROIDS WHICH HAVE BETTER SIDE EFFECT PROFILES POTENTIALLY. AND THEN ACTUALLY COVALENTLY LINKED ASPIRIN OR SAL SILLIC ACID AND ESSENTIALLY A DECKS HECKNOIC ACID OR O MEGA FISH OIL COMPOUND SYNERGISTICALLY WORKS H STACK INHIBITOR AND HAD -- FROM FIBROGENERAL, WHICH IS A HUMAN ANTI-CLONAL MONOCLONAL ANTIBODY THAT INHIBITS ACTIVITY CONNECTED TISSUE GROWTH FACTOR AS WELL. I WANT TO JUST POINT OUT ACTUALLY 22 YEARS AGO NCMRR HAD AN RFA IN PEDIATRIC REHABILITATION. THIS WAS ACTUALLY MY FIRST RO1 WAS PARTS OF THAT NCMRR RFA. THE PROJECT WAS FOCUSING ON ENERGY EXPENDITURE, WITH CHILDREN WITH MOBILITY IMPAIRMENT MUSCULAR DYSTROPHY, SPINA BIFIDA, CEREBRAL PALSY AND TYPICALLY DEVELOPED YOUTH, WE STARTED HAVING WEARABLES TO ACUTE MONITORING AND WE ARE DEVELOPING OUTCOME MEASURES AS END POINTS FOR CLINICAL TRIALS. FROM EFFORTS LED TO THE DESIGN CONDUCT OF THE SYNERGY COOPERATIVE NEUROMUSCULAR -- DUE SHEN STUDY THE LARGEST PER SPECK TV OF NATURAL HISTORY STUDY EVER CONDUCTED IN DUCHENNE. 400 PATIENTS FOLLOWED FOR TEN YEARS OR OR MORE. THIS ULTRAD IN MANY BLOOD BIOMARKERS DISCOVERED NOVEL CLINICAL END POINTS DEVELOPED IN PROGNOSTIC GENETIC POLYMORPHISMS IDENTIFIED. THERE'S BEEN MORE THAN 30 PUBLICATIONS FROM THIS EFFORT, IT STARTED WITH A NIDLER GRANT, WE THEN SUBSEQUENTLY WERE ABLE TO GIVE TWO RO1s FROM NIAMS TO CONDUCT THIS NATURAL HISTORY STUDY ADDITIONAL FUNDING FROM THE DEPARTMENT OF DEFENSE AND FUNDING FROM A PATIENT ADVOCACY GROUP AS WELL TO ALLOW US TO ACTUALLY CONDUCT THIS TEN YEAR NATURAL HISTORY STUDY OVER TIME. LAST YEAR WE PUBLISHED A PAPER IN THE LANSETT ON THE LONG TERM EFFECT OF STEROIDS ON FUNCTION QUALITY OF LIFE AND SURVIVAL. THIS STEROIDS ACTUALLY WILL TARGET AS I MENTIONED NF KAPPA B AND THERE ARE MICRORNAs IN MUSCLE MICROENVIRONMENTS THAT WILL CAUSE VARIABLE DYSTROPHIN EXPRESSION. MICRORNAs ARE ELEVATED IN MUSCLE FIBERS IN MUSCULAR DYSTROPHY PATIENTS. MICRORNA INCREASE WITH DISEASE SEVERITY AND THE INFLAMMATORY CYTOKINES INDUCE MICRORNAs IN THE ANTI-INFLAMMATORY BLOCK EXPRESSION OF THESE ROARK RNAs SO MICRORNAs PROVIDE PRECISION MEDICINE TARGET IN MUSCULAR DYSTROPHY AND IN EXON FOR STEROIDS TO WORK SYNERGISTICALLY. HERE WAS THE LONG TERM OUTCOME DATA LOOKING AT THE LONG TERM OUTCOMES IN THE PATIENTS TREATED WITH STEROIDS IN THE RED VERSUS BLUE THIS IS SURVIVAL DATA ON THE AGE OF LOSS OF AM BLEWLATION SO THERE'S A THREE AND A HALF YEAR PROLONGATION OF THE AGE LOSS OF AMBULATION AND DUCHENNE PATIENTS TREATED WITH STEROIDS BUT EVEN MORE STRIKING IS THE EXTRAPOLATION OF THIS TREATMENT BENEFIT TO ADULTS WITH DUCHENNE MUSCULAR DYSTROPHY, IF YOU FOLLOW THEM LONG ENOUGH AND LOOK WHAT AGE DID THEY LOSE DISTAL HAND FUNCTION IN STEROID TREATED VERSUS NON-STEROID TREATED POPULATION THE AVERAGE OF LOSS OF DISTAL HAND FUNCTION WAS 31 YEARS OF AGE IN STEROID TREATED PATIENTS AND 23 YEARS OF AGE IN NON-STEROID TREATED PATIENTS SO DEMONSTRATING POTENTIAL BENEFIT OF LONGER TERM AD MINUTEVATION OF STEROIDS. THEN SURVIVAL WISE THERE WAS 45 DEATHS THAT OCCURRED OVER TEN YEARS OF FOLLOW-UP, THE ODDS RATIO FOR THOSE ON STEROID TREATMENT IS SHOWN TO BE REDUCED BY OVER 50% WITH ODDS RATIO OF .47 IN THOSE THAT WERE TREATED WITH STEROIDS. I MENTION THE USE OF THE WEARABLE TECHNOLOGIES. IF YOU ARE FAMILIAR THAT STRIDE LENGTH CHANGES WITH PHYSICAL ACTIVITY WALKING SPEED WALKING, RUNNING, SPRINTING, BUT ALSO STRIDE LINK CHANGES WITH DEVELOPMENT AND ALSO IT CAN CHANGE IF HEIGHT IS STUNTED BY STEROIDS. IT GETS TO BE VERY COMPLICATED. SO WHAT WE HAVE DONE IN DUCHENNE IS LOOKED AT A STRIDE TO HEIGHT RATIO WHICH IS A DEVELOPMENTALLY ADJUSTED ANTHROPOE METRIC STANDARD. IF YOU LOOK AT THE LITERATURE GENERALLY WALKING THE STRIDE TO HEIGHT RATIO IN MOST HEALTHY INDIVIDUALS IS 0.8 SPEED WALKING 1 POINT 2, RUNNING 1.5 TO 1.9 AND SPRINTING IT APPROACHES TWO IN TERMS OF THAT STRIDE TO HEIGHT RATIO. WE ACTUALLY PERFORM STUDIES IN PATIENTS SEQUENTIALLY OVER TIME, AND FOUND STRIDE LENGTH DECREASES IN DUCHENNE WITH DISEASE PROGRESSION, IT INCREASES EVEN OVER PERIODS OF ONE YEAR WITH STEROID TREATMENT SO HERE IS A TYPICAL DUCHENNE GATE LUMBARDOSIS DIMINISHED STRIDE LENGTH OCCURRING OVER TIME, SO IN FACT WE LOOK AT STRIDE TO HEIGHT RATIO AND CORRELATED WITH STANDARD CLINICAL END POINTS SIX MINUTE WALK TEST THERE WAS A NICE LINEAR RELATIONSHIP, TEN METER WALK RUN TEST, THERE WAS A NICE LINEAR RELATIONSHIP WITH VIED TO HEIGHT RATIO THAT OCCURRED AND IF WE FOLLOW STRIDE TO HEIGHT RATIOS IN DUCHENNE PATIENTS THESE DATA POINTS ARE TYPICALLY DEVELOPING YOUTH. THESE ARE DUCHENNE PATIENTS YOU GET DIMINISHED STRIDE TO HEIGHT RATIO OCCUR OVER TIME IS DISEASE PROGRESSES. WHAT WE HAVE DONE IS WE HAVE THEN DEVELOPED WEARABLES THAT CAN MEASURE THE STRIDE LENGTH OF EACH VIED TAKE AND EACH STEP TAKEN. IF YOU LOOK AT THE TOTAL NUMBER OF STEPS THE DUCHENNE PATIENT TAKE OVERS COURSE OF A DAY THAT ARE NOT DIFFERENT FROM TYPICALLY DEVELOPING YOUTH. BUT INCORPORATING THE STRIDE LENGTH WHICH IS SENSITIVE FOR DISEASE PROGRESSION WE CAN MEASURE THE CADENCE, THERE'S A BELL SHAPED DISTRIBUTION OF CADENCE OVER THE COURSE OF THE DAY. STEPS PER MINUTE AND ACTUALLY IF YOU THEN LOOK AT THE METERS OR DISTANCE TRAVELED OF EACH CADENCE YOU CAN TAKE THE AREA UNDER THE CURVE WILL GIVE YOU THE TOTAL DISTANCE TRAVELED PER DAY AND COMMUNITY. BLUE DATA POINTS ARE TYPICALLY DEVELOPING YOUTH THESE ARE DUCHENNE PATIENTS, FOUR TO SIX YEARS OF AGE, SEVEN TO NINE YEARS OF AGE YOU CAN SEE THIS DECREMENT IN TERMS OF COMMUNITY DISTANCE TRAVELED, AS THE DISEASE PROGRESSESSER TEN TO 12 YEARS OF AGE THE SHIFT TO THE LEFT IN TERMS OF CADENCE VALUES AND ALSO MARKED DECREASE IN COMMUNITY DISTANCE. THIS APPROACH IS EMPLOYED NOW IN GENE THERAPY TRIALS THAT ARE BEING CONDUCTED. THIS IS JUST ANOTHER EXAMPLE OF THE DISEASE PROGRESSION OCCURS OVER THE COURSE OF THE DAY. WHAT ABOUT THE UPPER LIMB, MANY DUCHENNE FAMILIES AND PATIENTS ACTUALLY WHO ARE NON-AMBULATORY, THE CLINICAL TRIALS TYPICALLY FOCUS ON YOUNGER AMBULATORY PATIENTS, AND MUCH DUE TO LACK OF CLINICAL END POINTS. SO THE PHYSICAL THERAPY COMMUNITY PARTNERED WITH PATIENT GROUPS TO PROVIDE INPUT MANY TERMS OF WHAT WAS CLINICALLY MEANINGFUL AS WELL AS CLINICIAN SCIENTISTS AND CAME UP WITH THIS PERFORMANCE OF UPPER LIMB MEASURE TO ASSESS UPPER LIMB FUNCTION IN DUCHENNE DYSTROPHY. WE DID VALIDATION OF THIS, CONDUCTED NATURAL HISTORY STUDIES AND INDUSTRY IS NOW BEGUN TO CONDUCT CLINICAL TRIALS IN NON-AMBULATORY PATIENTS BECAUSE OF THE PRESENCE OF THIS UPPER LIMB OUTCOME MEASURES. JUST TO SHOW YOU AN EXAMPLE, THIS IS THE PERFORMANCE OF UPPER LIMB ENTRY ITEMS SO LESS IMPAIRED INDIVIDUAL FULL OVERHEAD REACH, THIS INDIVIDUAL HANDS TO THE SCALP, HANDS TO SHOULDER HEIGHT, THIS HERE IS A DISEASE PROGRESSES STILL GETTING WEIGHTED MOUTH. UNWEIGHTED HAND TO THE MOUTH AND LOSS OF DISTAL HAND FUNCTION. THERE WAS ACTUALLY A REGENERATIVE MEDICINE TRIAL, A TRIAL CONSISTING OF ALLOGENEIC DERIVED STEM CELLS INFUSE INTRAVENOUSLY, THESE CELL HONE TO THE VASCULTURE, THEY SECRETE EXOSOMES THEY CONTAIN NON-BINDING NON-CODING RNAs AND PROTEINS. THEY ARE INTERNALIZED AND IMMUNE MODULATING MITOCHONDRIAL FUNCTION IMPROVED REGENERATION AN DECREASED FIBROSIS. USING THIS PERFORMANCE OF UPPER LIMB PLACEBO CONTROL TRIAL SHOWING STATISTICALLY SIGNIFICANT IMPROVEMENT IN THE ELBOW FUNCTION MID LEVEL WITH STEM CELL REGENERATIVE MEDICINE. AND WE ARE ABLE TO LOOK AT COMPLETE PULL WHICH SHOULDER ELBOW AS WELL AS DISTAL HAND FUNCTION AS WELL AS OTHER ASPECTS OF POLE AND SHOWED AGAIN CONSISTENT TREATMENT BENEFITS VERSUS PLACEBO POPULATIONS. WE HAVE ALSO GONE ON BASED AN A NIAMS UO 1 GRANT, ONE OF MY FACULTY MEMBER AT UC URBINE USED THE XBOX CONNECTIBLE WORK SYSTEM TO REACH A WORK SPACE IN A NEUROMUSCULAR POPULATION, SHOWN TO CORRELATE NICELY WITH A BILL AND BEING USED FOR CLINICAL TRIALS IN ALS, SCAPULAR MUSCULAR DYSTROPHY AND OTHER. THE STOP CODON READ THROUGH COMPOUNDS, THESE NEW DNA LIKE MOLECULES OLIGONUCLEOTIDES WHICH TARGET SPECIFIC EXONS TO WHAT'S CALLED EXON SKIPPING WE WILL COMMENT ON MOMENTARILY, IN GENE THERAPY. A STOP CODON MUTATION PRODUCING A FUNCTIONAL PROTEIN, SO IN A NORMAL SITUATION YOU HAVE PA STOP CODON AND THE MEDICATION CAN ALLOW FOR READ THROUGH AND THEN THE PROTEIN WILL THEN BE ASSEMBLED WITH NORMAL TRANSLATION, GET A FULL LENGTH COPY OF THE DYSTROPHIN PROTEIN WITH THIS STOP CODON READ THROUGH COMPOUND. NOW, THIS WAS ACTUALLY STUDIED IN MULTI-CENTER CLINICAL TRIALS, IN A SUBPOPULATION. THERE WAS ACTUALLY A 42-METER TREATMENT BENEFIT ON THE DISTANCE, WE PUBLISHED THIS IN THE LANSETT, THIS MEDICATION HAS BEEN APPROVED NOW BY THE EUROPEAN MEDICINE AGENCY AND AVAILABLE COMMERCIALLY TO CHILDREN THROUGHOUT EUROPE. EXON SKIPPING IS REALLY VERY EXCITING MECHANISM OF ACTION THAT'S BEEN APPLY TO MUSCULAR DYSTROPHY PAT >> A STOP CODON MUTATION PRODUCING A FUNCTIONAL PROTEIN, SO IN A NORMAL SITUATION YOU HAVE PA STOP CODON AND THE MEDICATION CAN ALLOW FOR READ THROUGH AND THEN THE PROTEIN WILL THEN BE ASSEMBLED WITH NORMAL TRANSLATION, GET A FULL LENGTH COPY OF THE DYSTROPHIN PROTEIN WITH THIS STOP CODON READ THROUGH COMPOUND. NOW, THIS WAS ACTUALLY STUDIED IN MULTI-CENTER CLINICAL TRIALS, IN A SUBPOPULATION. THERE WAS ACTUALLY A 42-METER TREATMENT BENEFIT ON THE DISTANCE, WE PUBLISHED THIS IN THE LANSETT, THIS MEDICATION HAS BEEN APPROVED NOW BY THE EUROPEAN MEDICINE AGENCY AND AVAILABLE COMMERCIALLY TO CHILDREN THROUGHOUT EUROPE. EXON SKIPPING IS REALLY VERY EXCITING MECHANISM OF ACTION THAT'S BEEN APPLY TO MUSCULAR DYSTROPHY PATIENTS. HE'S A NORMAL DYSTROPHIN MESSENGER RNA, THERE'S 79 EXONS OR COATING SEQUENCES. THE RIBOSOME COMES ALONG, ACTUALLY ASSEMBLES A FULL LENGTH DYSTROPHIN PROTEIN, SIGNALS AMINO ACIDS INTO FULL LENGTH DYSTROPHIN PROTEIN. IN A EXON 48 TO 50 DELETION THERE'S DISRUPTION OF OPEN READING FRAME, THE RIBOSOME COMES AND STOPS PRODUCING THE FULL LENGTH DYSTROPHIN PROTEIN AND YOU END UP WITH A SHORTENED PROTEIN BECAUSE DOWNSTREAM THERE'S DISRUPTION OF THE READING FRAME. THAT PROTEIN ITSELF DOES NOT LACK THE NORMAL BINDING DOMAIN, IT'S UNSTABLE DISSENT GRATES SO YOU GET ABSENCE OF THE DYSTROPHIN PROTEIN BECAUSE OF THAT OUT OF FRAME MUTATION THAT OCCURS. IN THE SETTING OF EXON SKIPPING YOU TAKE A PHARMACOLOGIC AGENT, ESSENTIALLY TARGET EXON 51, COVER IT BRING THE MUTATION BACK INTO FRAME. THEN PRODUCING ESSENTIALLY A SHORTENED PROTEIN WITH NORMAL BINDING DOMAINS ON EITHER END. BUT A FUNCTIONAL PROTEIN THOUGH SHORTENED PROTEIN MUCH IS WHAT WE WOULD BE SEEN IN BECKER MUSCULAR DYSTROPHY. IT'S IMPORTANT TO KNOW THE GOAL OF EXON SKIPPING IS NOT TO PRODUCE A TRUE DUCHENNE PATIENT INTO A BECKER PHENOTYPE PATIENT, BECKER PATIENTS HAVE AVERAGE LIFE SPAN OF 67 YEARS, WORLDWIDE BUT THESE PATIENTS ACTUALLY HAVE EVERY ONE OF THEIR MUSCLE CELLS HAS THE INFRAME MUTATION FROM TIME OF FETAL DEVELOPMENT, IT'S NOT REALISTIC TO THINK WE'LL TREAT DUCHENNE PATIENTS AT AGE FOUR OR FIVE AND CREATE A BECKER PHENOTYPE. BUT THE GOAL HERE OF EXON SKIPPING IS PRODUCING LOW LEVELS OF SHORTENED DYSTROPHIN TO SLOW DISEASE PROGRESSION. HERE IS MUSCLE BIOPSIES BEFORE AND AFTER TREATMENT SHOWING ON IMMUNOHISTOCHEMISTRY THE PRODUCTION OF DYSTROPHIN PROTEIN WITH EXON SKIPPING DRUG TARGETING EXON 51. THIS STUDIES HAVE SHOWN WITH A VARIETY OF MUSCLE BIOPSY QUANTITATION TECHNIQUES ACTUAL PRODUCTION OF THE DYSTROPHIN PROTEIN LISTED SIGNIFICANTLY SIGNIFICANT FOLD INCREASES. INTERESTINGLY THE DYSTROPHIN PRODUCTION, TAKES ABOUT A YEAR FOR THE DYSTROPHIN PROTEIN TO REALLY BE PRODUCED AT EVEN LOW LEVELS. INTERESTINGLY IF YOU LOOK AT THE CLINICAL DATA, SIX MINUTE WALK TEST YOU SEE DIVERGENCE AFTER A YEAR, FOUR SPOT CAPACITY, AGAIN DIVERGENCE AFTER YEAR'S TIME AND THE PATIENTS, THERE'S INITIAL EARLY LOSS OF AMBULATION BUT THE TREATED PATIENTS ACTUALLY HAVE HAD PROLONGED AMBULATION OUT TO FOUR YEARS WITH THIS METHODOLOGY. AGAIN, HERE IS DATA ACTUALLY USING OUR NIH FUNDED SYNERGY NATURAL HISTORY DATA LOOKING AT THE NATURAL HISTORY OF LOSS OF AMBULATION IN AN EXON 51 SKIP AMENABLE POPULATION VERSUS TREATED PATIENTS, AGAIN SHOWING DIFFERENCES. SO HERE AGAIN IS THIS 8-YEAR-OLD PATIENT, REMINDING YOU RUNNING ON THE TEN METER WALK RUN TEST. THIS IS THE YOUNGEST THREE PATIENTS THAT I TREATED WITH A DRUG CALLED A -- AN EXON SKIPPING DRUG, THE YOUNGSTER ON THE RIGHT IS TEN YEARS OF AGE, HAS BEEN ON THE DRUG FOR ALMOST FOUR YEARS 8 1/2-YEAR-OLD, THESE ARE RECENT VIDEOS TAKEN STILL ABLE TO RUN 8 1/2 YEARS, ALMOST FOUR YEARS ON THE DRUG. AND HERE IS A PATIENT LITERALLY RUNNING THE SIX MINUTE WALK TEST CORRIDOR. WHO HAS BEEN ON -- 7 1/2 YEARS OF AGE, BEEN ON THE DRUG FOR ABOUT THREE YEARS OF AGE. AGAIN WITH REGARD TO THE MORE SEVERELY AFFECTED PATIENTS, OUR NATURAL HISTORY DATA SHOWS A FAIRLY LINEAR DECLINE IN BREATHING CAPACITY FOUR SPOTTED CAPACITY BETWEEN TEN AND 18 YEARS OF AGE. IN FACT IF YOU LOOK AT THE PATIENTS WHO ARE NON-AMBULATORY TREATED WITH EXON SKIPPING DRUG, OUR SYNERGY NATURAL HISTORY DATA SHOWED 6% DECLINE PER YEAR AND ALSO ABOUT A 40 TO 50% REDUCTION IN THE RATE OF DECLINE IN FOUR SPOTTED CAPACITY IN THE EXON SKIPPING TREATED PATIENTS ACROSS THREE DIFFERENT STUDIES. AGAIN SHOWING POTENTIAL BENEFIT FOR THIS PRECISION MEDICINE THERAPEUTIC TO IMPROVE PULMONARY FUNCTION AND SLOW THE RATE OF DECLINE AND TIME TO NEEDING MECHANICAL VENTILATION. AGAIN, THERE'S VARIETY OF COMPANIES THAT ARE IN THIS SPACE THAT ARE DEVELOPING A VARIETY OF EXON SKIPPING AGENTS TARGETING SPECIFIC GENE MUTATIONS. SOME OF THESE HAVE BEEN OPTIMIZED AND SOME OF THEM ARE ACTUALLY COMMERCIALLY AVAILABLE, OTHERS THAT TARGET STOP CODON MUTATIONS. BUT THERE'S ABOUT 30% OF ALL DUCHENNE PATIENTS CAN ACTUALLY BE POTENTIALLY TREATED WITH THESE EXON SKIPPING DRUGS THAT ARE IN LATE STAGE CLINICAL DEVELOPMENT. ULTIMATELY ABOUT 70 TO 80% OF ALL DUCHENNE PATIENTS COULD BE TREATED BY EXON SKIPPING APPROACH. HERE IS ANOTHER ONE, EXON 53 SKIPPING APPROACH SHOWING AN ACTUAL IMPROVEMENT IN THE NORTHERN STAR AMBULATORY ASSESSMENT AND TEN METER WALK RUN TEST VERSUS SYNERGY NIH FUNDED NATURAL HISTORY DATA HERE. I WANT TO COMMENT BRIEFLY ABOUT MICRODYSTROPHIN GENE THERAPY. IN DUCHENNE, THIS IS ACTUALLY A DYSTROPIC DOING THAT LACKS DISAVOW FIN. THIS IS A GOLDEN RETRIEVER MODEL, THEY HAVE DIFFICULTY HOLDING UP THEIR HEAD AND JUMPING. THANS ACTUAL DOG TREATED WITH AAB MICRODYSTROPHIN GENE THERAPY AFTER SEVEN MONTHS. YOU CAN SEE IT'S A PRETTY DRAMATIC CLINICAL DIFFERENCE THERE. THERE'S ACTUALLY THREE ONGOING TRIALS THAT WILL BE BEGINNING NEXT YEAR THAT ARE FOCUSING ON DUCHENNE DYSTROPHY WITH THIS MICRODYSTROPHIN GENE THERAPY APPROACH. THE ESSENTIAL COMPONENTS OF GENE THERAPY IS PRESENCE OF VECTOR, YOU HAVE TO HAVE THE RIGHT VECTOR TO DELIVER THE TRANSGENE TO TARGET CELLS WITH AMENABLE IMMUNE RESPONSE. A PROMOTER THAT DRIVES EXPRESSION INTO THE INTENDED TISSUES. AND THEN A TRANSGENE THAT PRODUCES A FUNCTIONAL VERSION OF THE PROTEIN OF INTEREST. SO THERE'S A NUMBER OF CRITICAL PROTEIN DOMAINS, THE BINDING DOMAINS THAT EITHER END AND HINGE REGIONS OF THE DOMAIN THAT CORRESPOND TO CERTAIN EXONS OF THE DYSTROPHIN GENE, THE LARGEST GENE IDENTIFIED IN THE HUMAN GENOME. PART OF THE PROBLEM IS THAT THE FULL LENGTH DISAVOW FIN GENE IS TOO LARGE TO PACKAGE INTO AN AAV. SO HERE IS THE DYSTROPHIN PROTEIN, THE COPY DNA ABOUT 14,000-KILO BASES. THE AAB CAPACITY IS ABOUT 30% OF THAT. SO THE AAV CAPACITY IS -- SO YOU HAVE TO DECIDE IN TRYING TO PACKAGE THIS ALL IN WHAT IS ESSENTIAL TO PACKAGE AND DELIVER AND WHAT DO YOU HAVE TO DECIDE YOU ARE NOT GOING TO BE ABLE TO FIT INTO THE LUGGAGE HERE. SO WHAT WAS DONE IS YEARS AGO A PATIENT WAS IDENTIFIED 61-YEAR-OLD PATIENT WITH MILD BECKER MUSCULAR DYSTROPHY WHO ACTUALLY HAD A LARGE DELETION FROM EXON 17 TO 59. THERE'S A TOTAL OF 79 EXONS BUT THIS PATIENT HAD A HUGE DELETION BUT THEY HAD THIS SMALL DYSTROPHIN WHICH IS ACTUALLY HAD THE CRITICAL COMPONENTS TO MAINTAIN FUNCTION BUT WAS MUCH SMALLER AND THAT'S BEEN THE MODEL FOR THESE MICRODISAVOW FINS THAT ARE -- DYSTROPHINS PACKAGED INTO THE, AAV. THIS IS AN EXAMPLE OF ONE, THERE'S A CRITICAL COMPONENTS MAINTAINED TO BIND THE INTRACELLULAR ACTIN DOMAIN AS WELL AS THE TRANSMEMBRANE DYSTROPHIN ASSOCIATED PROTEINS HERE ACROSS THE MUSCLE MEMBRANE. AND AGAIN, THESE MICRODYSTROPHIN CONSTRUCTS FIT INTO AN AAV VIRUS, THERE'S THIS CRITICAL COMPONENTS OF THIS SMALL MICRODYSTROPHIN, THAT BIND TO THE CYTOSKELETON INTERNALLY, BINDS TO THE TRANSMEMBRANE PROTEINS, THERE'S HINGE REASONS FOR FLEXIBILITY REGIONS THAT BIND TO MAINTAIN CONTRACTILE FORCE AND OTHER REGION FOR MICROTUBULE ORGANIZATION. IN THE EARLY STUDIES HERE OF PATIENTS, THE FIRST FOUR PATIENTS TREATED WITH THE MICRODISAVOW FIN YOU CAN SEE ACTUAL HOE MICRODYSTROPHIN YOU CAN SEAL DYSTROPHIN PRODUCTION OF ABOUT 80% FIBERS SHOWING MICRODYSTROPHIN EXPRESSION WITH IV SINGLE DOSE OF IV TREATMENT. SO IT'S ESSENTIALLY A SINGLE DOSE TREATMENT, BECAUSE OF THE IMMUNOLOGIC RESPONSES. THE MUSCLE MEMBRANES IN THESE PATIENTS THE CK IS QUITE ELEVATED AT NEARLY 30,000 BECAUSE CK IS SPILLED INTO THE BLOODSTREAM. THE CK LEVELS OF THESE PATIENTS WENT FROM 27,000 DOWN TO 2700 AND MAINTAINED A STABLE RANGE AND LOWER VALUE, NOT NORMAL, NORMAL CKs ARE FROM ABOUT 200 TO 300. AND THEN AGAIN, THE NOR STAR AMBULATORY ASSESSMENT DEVELOPED BY PHYSICAL THERAPISTS SHOWED SOME TRENDS TOWARDS IMPROVEMENT IN THESE FIRST PATIENTS TREATED. BUT AGAIN WE -- SAFETY IS UNKNOWN, WE DON'T KNOW DURABILITY OF EFFECT. THE ANTIBODY TITERS AFFECT PATIENT ELIGIBILITY, 15% OF PATIENTS HAVE ANTIBODIES TO THESE AAB VECTORS. THE DOSES THAT MAY BE DIFFERENT BETWEEN DIFFERENT CONSTRUCTS, WE DON'T KNOW IF THE AAV GENE THERAPY GETS INTO THE SATELLITE CELLS WHICH ARE CRITICAL FOR MUSCLE, LONG TERM MUSCLE REGENERATION AND MUSCLES ARE A PRETTY DYNAMIC TISSUE THAT TURNS OVER. AND THEN FINALLY I JUST LIKE TO FINISH BY TALKING ABOUT SOME NEW EMERGING THERAPEUTIC STRATEGIES FOR TREATING SPINAL MUSCULAR ATROPHY. SO THE SMA, THIS IS ACTUALLY THE MOST COMMON GENETIC CAUSE OF DEATH IN CHILDREN. THE SPINAL MUSCULAR ATROPHY GENE IS LOCATED ON CHROMOSOME 5. THERE'S ACTUALLY TWO GENES AT THAT LOCUST, THE SURVIVAL MOTOR NEURON GENE 1 AND THE GENE 2, THE GENE 1 IS ACTUALLY THE CAUSATIVE GENE AND MOTOR NEURON 2 MODIFY IT IS SEVERITY OF THE GENE SO THE SURVIVAL MOTOR NEURON PROTEIN IS ACTUALLY CRITICAL FOR THE HEALTH OF MOTOR NEURONS ANTERIOR HORN CELLS, CRITICAL TO HELP ASSEMBLE THE CELLULAR MACHINERY TO PROCESS PRE-mRNA THE DEFICIENCY CAUSES WIDESPREAD SPLICING DEFECTS, ESPECIALLY IN SPINAL MOTOR NEURONS, IMPORTANT FOR DEVELOPMENT OF YOUTH GROWTH FROM NERVE CELLS SPECIFICALLY DENDRITES AND AXONS. THERE'S THREE TYPES OF SPINAL MUSCULAR ATROPHY, THE MOST SEVERE FORM IS ACUTE INFANTILE FORM OR WORD IN COMP SMA ONE PATIENT VERSUS AGE OF ONSET LESS THAN SIX MONTHS WITH MEAN AGE ONSET OF A LITTLE OVER ONE MONTH. THEY HAVE SHORT LIFE EXPECTANCY, THE MEDIAN EVENT FREE SURVIVAL 10.5 MONTHS, THAT'S DEFINED AS TIME TO REQUIRING AT LEAST 16 HOURS OF VENTILATION FOR 14 CONSERVATIVE DAYS. THESE PATIENTS NEVER DEVELOP HEAD CONTROL, NEVER ABLE TO SIT. MOST OF THEM HAVE TWO COPIES OF THIS OTHER GENE, SURVIVAL MOTOR NEURON 2 GENE WHICH THE SMN 2 ACTUALLY MODULATES THE SEVERITY OF THE GENE. THEN THERE'S SMA 2, THE INTERMEDIATE FORM, THESE PATIENTS USUALLY REQUIRE POWER WHEELCHAIRS, AGE ONSET BETWEEN SIX MONTHS AND 18 MONTHS. IF SHORTENED LIFE EXPECTANCY BUT THEY LIVE INTO 20s TO 40s, THEY REQUIRE NOCTURNAL HYPERVENTILATION, THEY HAVE GOOD HEAD CONTROL AND ABLE TO SIT BUT USUALLY CANNOT EVER DEVELOP ABILITY TO WALK. MOST OF THESE PATIENTS HAVE THREE COPIES OF THE SMN 2 GENE AND THEN THE JUVENILE FORM SMA 3, THESE PATIENTS PRESENT LATER USUALLY AFTER 18 MONTHS TO THREE YEARS. IF NORMAL LIFE EXPECTANCY. THEY ARE ABLE TO WALK BUT DECLINING AMBULATORY ACT THAT OCCURS. AND THESE PATIENTS HAVE THREE OR FOUR COPIES OF THE SMN 2 GENE. HERE IS SMN 1, CAUSATIVE GENE. THAT'S ACTUALLY IN ABOUT 96% OF PATIENTS, THEY HAVE A HOMOZYGOUS ABSENCE AFTER EXONS 7 AND 8 OR ONLY EXON 7 OF THAT GENE. THEN THERE'S THIS GENE THAT IS NORMALLY SILENCED THAT'S A MODULATING GENE THAT ACTUALLY MOTOR UNIT NUMBER ESTIMATION, SMA 1 PATIENTS HAVE THIS RAPID DROP OFF WITHIN THE FIRST THREE MONTHS IN TERMS OF MOTOR UNITS SMA 2 IS A BIT LATER VERSUS NORMAL. AGAIN THE PHYSICAL THERAPY AND REHABILITATION COMMUNITY CAME THROUGH AND DEVELOPED THE WHAT'S CALLED THE CHILDREN'S HOSPITAL PHILADELPHIA INFANT TEST OF NEUROMUSCULAR DISORDERS, FOUR POINT RATING SCALE ON 16 DOMAINS, THIS IS JUST TWO DOMAINS OF UPPER LIMB SPONTANEOUS MOVEMENT IN THE SUPINE POSITION AND LOWER EXTREMITY SPONTANEOUS MOVEMENT IN SUPINE POSITION. THERE'S 16 DOMAINS. THEY CHOP AND TEND ACTUALLY DEVELOPED BY PHYSICAL THERAPISTS TOTAL RANGE FROM 0 TO 64. A CHOPPING TEN SCORE GREATER THAN 40 IS RARELY SEEN IN TYPE 1 INFANTILE FORM OF SMA AND THESE ARE JUST EXAMPLE OF 16 DIFFERENT DOMAINS. AGAIN WITH THE NEURONEXT NETWORK THERE'S ACTUALLY A NIH FUNDED NATURAL HISTORY STUDY IN SMA CONDUCTED THROUGH THE NEURONEXT NETWORK WHERE WE COLLECTED DATA AND HEALTHY TYPICALLY DEVELOPING PATIENTS USING A VARIETY OF MEASURES, THE CHOP AND TEND, TEST OF INFANT MOTOR PERFORMANCE, THE AIMS OR THE ALBERTA INFAN MOTOR SCREENING EVALUATION, ELECTROPHYSIOLOGIC MEASURES, THIS NATURAL HISTORY DATA PERFORM TOED A BASIS WITH COMPARISON WITH NEW THERAPEUTICS. THEN AGAIN THE HAMMER SMITH INFANT DEVELOPMENT IS A MORE MILESTONE BASED MEASURE LOOKING AT MILESTONES OF HEAD CONTROL SITTING, VOLUNTARY GRAPH ABILITY TO KICK ROLL, CRAWL, STAND OR WALK. THESE ARE THE MILESTONES USED. AGAIN THIS WAS DEVELOPED BY THE REHABILITATION PHYSICAL THERAPY COMMUNITY AND VALIDATED IN NATURAL HISTORY INVESTIGATION. THERE'S A JEAN THERAPY APPROACH TO TREAT SMA WHICH TAKES A FULL LENGTH SMA GENE MUCH SMALLER THAN THE DUCHENNE GENE SO YOU CAN PUT THE FULL LENGTH COPY OF THE GENE INTO A AAB CAPSID IN THIS CASE AAV 9. THIS WAS THE STUDY PUBLISHED IN NEW ENGLAND JOURNAL BY DR. JERRY MENDEL AND TEAM, SINGLE DOSE GENE REPLACEMENT THERAPY, IT ONLY REQUIRED A SINGLE DOSE BY ADMINISTRATION TO TREAT SPINAL MUSCULAR ATROPHY, ONE WAS LATER IN ONSET SIX MONTHS THEY WERE TREATED, THE OTHER GROUP WAS TREATED WITH HIGHER DOSE EARLIER 3.4 MONTHS OF AGE. WHAT WAS QUITE STRIKING THOUGH WAS THE DURATION, THIS WAS THE 15 PATIENTS WERE TREATED, THE DURATION OF SURVIVAL FREE FROM PERMANENT VENTILATION LITERALLY EVERY ONE OF THESE PATIENTS IS MAINTAINED STATUS WITHOUT NEED FOR VENTILATION AT 20 MONTHS OF AGE NATURAL HISTORY DATA SHOWS 8% RATE OF EVENT FREE SURVIVAL IN TERMS OF VIRTUALLY 92% OF PATIENTS GENERALLY REQUIREMENT VENTILATION ALL 15 PATIENTS CONTINUE WITHOUT THE NEED FOR MECHANICAL VENTILATION. CHOPPING TEND DATA SHOWED IMPROVEMENT IN THESE PATIENTS. THIS IS THE COHORT THAT WERE TREATED EARLIER. WITHIN THE FIRST THREE MONTHS. THIS IS IS THE DATA CHOPPING TEN DATA FROM THE THREE SUBJECTS TREATED AFTER SIX MONTHS OF AGE. THIS WILL IS FORMED THE BASIS NOW FOR FDA APPROVAL AND THE APPLICATION OF NEWBORN SCREENING WHICH IS NOW MANDATED IN SPINAL MUSCULAR ATROPHY AND BEING ROLLED OUT IN ALL ACROSS THE UNITED STATES. THIS IS AGAIN, THE MILESTONES DEVELOPED IN THESE 15 PATIENTS TREATED VIRTUALLY ON NONE OF THE NATURAL HISTORY PATIENTS, EVER ACHIEVE ANY OF THESE MILESTONES, THESE MILESTONES ARE ACHIEVED IN ANYWHERE FROM 58% TO 100% PATIENTS TREATED. WITH GENE THERAPY. AGAIN, THE OUTCOMES ON THE CHOP AND TEN VERSUS NIH FUNDED NATURAL HISTORY DATA, FROM THE NEURONEXT NETWORK HERE IS THE NATURAL HISTORY DATA CHOP AND TEND ON TREATED PATIENTS. THIS IS THE CHANGE IN THE CHOP AND TEN SCORE COMPARED TO THE GENE THERAPY TREATED PATIENTS. I WILL JUST SHOW YOU A BRIEF VIDEO HERE PRODUCED -- SPINAL MUSCULAR ATROPHY OR SMA -- >> THIS IS THEIR FIRST CHILD, BABY JOSEPHINE. ONE TIME INJECTION GENE THERAPY REPLACES THIS MISSING GENE. FOR EVELYN THIS GENE THERAPY WORKED. >> WE START SEEING CHANGES AS FEW MONTHS (INAUDIBLE) PUSH AS SHE STARTED TO GET MORE ACCURATE PULLING HER HEAD UP. (OFF MIC) >> TO A DANCE OFF AT HER ANNUAL FOLLOW-UP APPOINTMENT. >> SHE COMES BACK AFTER THREE YEARS AND SHE RUNS UP TO ME AND HUGS ME AND SAYS DR. MENDEL I LOVE YOU. >> I FORGET SHE HAS S MARKS. THIS IS -- SMA. THIS THIS IS A HEALTHY GIRL AND DOES EVERYTHING A NORMAL THREE-YEAR-OLD CHILD WOULD DO. >> SOMETHING LIKE THAT HAS NEVER BEEN ACHIEVED BEFORE. >> WITH OUR FIRST DAUGHTER IT WAS JUST DEVASTATING TO LOSE A CHILD YOU LOSE ALL DREAMS YOU HAVE FOR THEIR FUTURE. AND NOW WE CAN ACTUALLY SAVE FOR COLLEGE Z. >> SO YOU CAN SEE THE REALLY DRAMATIC AND PHENOMENAL OUTCOME. THERE'S ANOTHER MEDICATION THAT IS TARGETS THE SMN 2 GENE DELIVERED INTRAFECALLY, IT'S AN ANTI-SENSE OLIGONUCLEOTIDE, WHICH TARGETS THE MESSENGER RNA ALTERNATIVE SPLICING TO GET ESSENTIALLY THE SMN 2 GENE TO START PRODUCING MEANINGFUL LEVELS OF SURVIVAL MOTOR NEURON PROTEIN. THIS HAS BEEN FDA APPROVED NOW SINCE 2016. AGAIN, THIS ANTI-SENSE OLIGONUCLEOTIDE IS HAVE DELIVERED ANTI-THECALLY. THE INTRON OR NON-CODE REGULAR GENERAL WHICH AFFECTS THE ALTERNATIVE SPLICING TO GET EXON 7 TO BE ESSENTIALLY ENGAGED AND FULL LENGTH PROTEIN SMN 2 PROTEIN IS PRODUCED. AND AGAIN, THIS WAS PUBLISH BY DR. FENKAL AND COLLEAGUES IN THE NEW ENGLAND JOURNAL, VERSUS SHAM CONTROLLEN FAN TILE ONSET SPINAL MUSCULAR ATROPHY, THIS WAS MEASURES BY HAMMER SMITH INFANT NEUROLOGIC EXAMINATION, THE DATA POINTS IN UPPER DIRECTION ARE ALL TREATED PATIENTS, TWO TO ONE RANDOMIZATION, A MEAN CHANGE OF FOUR POINTS IN TERMS OF ACHIEVED MILESTONES IN HAMMER SMITH AND LOSS OF MILESTONES IN UNTREATED PLACEBO PATIENTS. THIS STUDY WAS STOPPED ON INTERIM ANALYSIS AND THE FDA GAVE A RAPID APPROVAL. THIS WAS THE ACTUAL DATA ON EVENT-FREE OR SURVIVAL SHOWING PORTION OF INFANTS ALIVE WITHOUT USE OF PERMANENT ASSISTED VENTILATION. TREATED WITH GENE THERAPY OR WITH NURSE -- VERSUS CONTROL. THEN NURSING NURSING IN TERMS OF OVERALL SURVIVAL VERSUS CONTROL POPULATION. THE -- VERSUS LATE ONSET SPINAL MUSCULAR AROW MY IS PATIENTS WITH ONSET OF THE DISEASE AFTER SIX MONTHS OF AGE, THESE ARE THE TYPE 2 PATIENTS AND THEY CONTINUE TO ACTUALLY GAIN FUNCTION BASED ON THE HAMMER SMITH IN RELATION TO PLACEBO TREATED PATIENTS OR REVISED UPPER LIMB MODULE DEVELOPED BY PHYSICAL THERAPIST OCCUPATIONAL THERAPISTS SHOW CONTINUED IMPROVEMENT VERSUS THE SHAM TREATED PLACEBO POPULATION. AND THEN EVEN LOOKING AT LONGER TERM FOLLOW-UP THESE PATIENTS ARE CONTINUING TO GAIN MILESTONES WHEN FOLLOWED OUT TO OVER THREE YEARS IN PATIENTS WITH BOTH SMA TYPE 2 AND SMA TYPE 3 AGAIN SHOWING LONGER TERM BENEFIT MANY THESE PATIENTS. THAT LONGER TERM FOLLOW-UP THIS WAS PUBLISHED IN THE JOURNAL OF NEUROLOGY FROM HARVARD. AGAIN CONTINUED IMPROVEMENT IN THE UP PER LIMB MODULE AND ACTUAL IMPROVEMENT IN SIX MINUTE WALK TEST IN THOSE AMBULATORY PATIENTS TREATED WITH SPIN OZER AND NURSINUSIN. WHEN YOU TREAT PATIENTS PRE-SYMPTOM@ICALLY IN FEW WEEKS OF AGE SOME OF THOSE PATIENTS WITH ONLY TWO COPIES OF SMN 2 THOSE PATIENTS THAT ARE DESTINED TO BE ACUTE INFANTILE FORM WE USUALLY REQUIRE VENTILATION BY AGE TEN MONTHS. THERE'S ACTUALLY ONE PATIENT DEVELOP THE ABILITY TO WALK TWO OUT OF NINE DEVELOP STANDING AND FOUR DEVELOPED SITTING. FIVE DEVELOPED HEAD CONTROL. SO AGAIN, VERY ENCOURAGING RESULTS THERE. AND I WANT TO JUST END BY JUST OBVIOUSLY WITH SPINAL MUSCULAR ATROPHY THERE IS -- WITH MANY OF THESE CHILDREN TREATED LATER IN THE COURSE OF THE DISEASE, IT'S NOT A CURE, THIS WAS ACTUALLY OUR EXPERIENCE WITH USE OF ROBOTICS. THIS IS A VIDEO THAT ACTUALLY ONE OF MY PATIENTS PRODUCED FIVE YEARS AGO. >> MY NAME IS LAURA BASH. I'M 16-YEAR-OLD OLD. I LIVE IN DIXON, IT'S A LITTLE TOWN IN NORTHERN CALIFORNIA. SACRAMENTO, MOSTLY WHAT WE HAVE HERE IS FARMERS, WE ARE LUCKY THERE. THERE YOU GO. I WAS GOING WITH THE GENETIC CONDITION CALLED SPINAL MUSCULAR ATROPHY. I WAS A MILITARY CHILD FOR MOST OF MY LIFE. SO I HAVE BEEN AROUND THE COUNTRY. WHENEVER I MOVE I'M MORE MEDICAL TEAM AND PEOPLE HERE IN CALIFORNIA, AT UC DAVIS HAVE BEEN WONDERFUL. I FIRST LEARNED ABOUT MUSCULAR DYSTROPHY ASSOCIATION WHEN I WAS IN HOY HIGH SO I GOT TO GO TO MY FIRST SUMMER CAMP ON THE BEACH. THERE'S -- THOSE CAMPS BECAUSE IT'S FOR PEOPLE WITH WHEELCHAIRS, IT'S FOR MUSCULAR DYSTROPHY. THERE ARE PEOPLE WILLING TO HELP YOU DO WHATEVER YOU WANT TO DO. I HAVE ALWAYS HAD A GREAT TIME AT HOSE CAMPS IT WAS ACTUALLY THROUGH MUSCULAR DYSTROPHY ASSOCIATION THAT I GOT MY FIRST TASTE OF --. >> WHAT IS IT LIKE RAISING THE WORLD'S MOST INDEPENDENT PERSON? HAPPENS TO BE IN DISABLED BODY? IT CAN BE DIFFICULT SO WE HAVE LOOKED THROUGHOUT LAURA'S LIFE FOR OPPORTUNITIES TO GAIN GREATER INDEPENDENCE. GOT SERVICE DOG OPENED UP HUGE DOORS FOR HER AND SHE CAME HOME AND SAID SHE WAS GOING TO GET JAKO AND THAT'S BEEN AMAZING. BECAUSE OF ALL THE THINGS SHE CAN NOW DO SHE'LL KICK OFF ON HER OWN, I HAVE MORE CONFIDENCE SHE IS GOING TO SUCCEED AND BE ABLE TO COME HOME AND -- NOT DIE. NOT DYING. >> A LOT (INAUDIBLE) HIGH SCHOOL WITH MY HONORS AND AP CLASSES AND I FIND -- USEFUL FOR VARIOUS PROJECTS. FOR INSTANCE IF I NEED HELP WITH CALCULUS PROBLEM, MIGHT HELP ME RAISE MY HAND. I WANTED TO DRAW (INAUDIBLE) CLASS I HAVE (INAUDIBLE) TO USE A PENCIL WITH MY FREE HAND. I HAVE ALWAYS HAD A ROUGH TIME WITH MAILBOXES, WE HAVE ONE OF THE ONES WHERE IT'S GOT A BUNCH OF LITTLE STACKED METAL BOXES NEXT TO EACH OTHER, OURS IS HIGH UP OFF THE GROUND, HARD FOR ME TO GET UP. WITHIN DAY I WANTED TO SEE IF I CAN DO IT WITH -- SO I TOOK SET OUT OF THE HOUSE BY MYSELF AND AND WENT DOWN. TOOK A WHILE THE GET RIGHT BUT I USED JA CORKS, TO GET THE KEY UP PUT IT IN THE LOCK TURN IT OPEN THE DOOR AND GET THE MAIL OUT, ON MY OWN. BEFORE JAKO I WAS DEPENDENT ON OTHERS OUT IN PUBLIC. FOR INSTANCE IF I WERE TO DROP SOMETHING ON THE GROUND I WOULDN'T NECESSARILY BE ABLE TO GET IT BACK ON MY OWN. GOING SHOPPING ON MY OWN WAS OUT OF QUESTION. MOST OF THE OBJECTS ON SHELVES AND RACS ARE -- TOO FAR OUT OF MY REACH. WITH J AKO THAT COMPLETELY CHANGED WHERE TO THE POINT I'M OUT AND ABOUT I CAN CALL AND SAY HEY DO YOU NIGHED ANYTHING FROM THE STORE, IF SHE NEEDS SOMETHING I CAN GO IN USE JAKO TO GET IT OFF THE SHELF. NO PROBLEM. I CAN BE OUT BY MYSELF AND I FEEL LIKE I'M GOING TO BE ABLE TO GET ON MY OWN WHEN I NEED TO BE ON MY OWN. >> I KNOW LAURA HAS PLANS SHE HAS PLANS, SHE'S WOOED BY UNIVERSITIES ALL OVER THE COUNTRY WHICH IS DIFFICULT FOR ME AS MOTHER TO EVEN CONTEMPLATE BUT I KNOW SHE HAS JAKO (PHONETIC) AND I KNOW SHE CAN OPEN DOORS. SHE CAN GET BOOKS IF SHE NEEDS THEM. I KNOW SHE CAN PREPARE FOOD IF SHE NEEDS TO. SO MANY THINGS HAVE GIVEN GREAT CONFIDENCE TO LOOK FORWARD TO HER FUTURE. >> I'M NOT THE ONLY ONE IN THE WORLD WHO WANTS INDEPENDENCE. I THINK IT'S A VERY UNIVERSAL DREAM AND SOMETHING THAT EVERYONE -- NEEDS IN SOMETHING DISABLED PEOPLE JUST CAN'T HAVE. SOMETHING I DIDN'T HAVE FOR MOST OF MY LIFE, WHICH IS WHY TO ME IT'S SO IMPORTANT THE SEARCH BE DONE AND FOUNDING WAYS TO GET JAKO OUT THERE TO MAKE SURE EVERYONE WHO COULD NEED IT HAS ACCESS TO IT. IT CAN CHANGE SO MANY LIVES THAN JUST THE WAY IT CHANGED MINE. WITH THAT I'LL CONCLUDE. WE HAVE TIME FOR COUPLE OF QUESTIONS. THANK YOU. [APPLAUSE] >> THE GENE SKIPPING AND THE MICROGENE THERAPY EXPERIMENTS, ARE THERE ACTIVITY MEDIATED STRATEGIES THAT ACTUALLY FACILITATE THEM GETTING A FOOTHOLD AND IMPROVING FUNCTION SOONER? DOES THAT MAKE ANY DIFFERENCE? >> YOU MEAN A COMBINATION OF ACTIVITY BASED STRATEGIES IN ADDITION TO -- >> THE GENE THERAPY. >> GENE THERAPY? I THINK THERE'S SOME EVIDENCE THAT MAYBE EXON SKIPPING MAY BE MORE ADEQUATELY TAKEN UP IN MUSCLE FIBERS WITH PHYSICAL ACTIVITY SO H'S BEEN SOME LOOK INTO THAT BUT I THINK CERTAINLY I THINK THESE PATIENTS STILL HAVE A FAIR AMOUNT OF IMPAIRMENT AND I THINK ACTIVITY BASED APPROACHES ARE GOING TO BE IMPORTANT TO CONTINUE TO AUGMENT THEIR FUNCTIONAL OUTCOMES AND FUNCTIONAL CAPACITY. IT HASN'T REALLY BEEN LOOKED AT WITH REGARD TO THE ONE TIME TREATMENT OF AAV GENE THERAPY BOTH IN SPINAL MUSCULAR ATROPHY OR IN DUCHENNE MUSCULAR DYSTROPHY. THAT'S A GREAT QUESTION. >> JUST FOLLOWING UP ON THAT, WHAT'S THE THINKING ABOUT THE LEVEL OF ACTIVITY THAT'S NEEDED TO DAMAGE THE FIBER? IS THERE LIKE DATA ON THAT? THE KIDS RUN -- IS THAT -- >> I THINK THERE'S BEEN MOSTLY IT'S HIGH RESISTANCE LOADS PARTICULARLY E CENTRIC INDUCED CONTRACTIONS, THERE'S BEEN DATA TO SUGGEST DECREASE IN STRENGTH WITH HIGHER RESISTANCE LOADS BUT THERE'S ALSO WORK DONE WHERE PATIENTS HAVE BEEN SHOWN TO HAVE BETTER FUNCTIONAL OUTCOMES WHEN ENGAGED IN AEROBIC PROGRAM. THE MOST THINKING IS THAT PHYSICAL ACTIVITY IS GENERALLY FELT TO BE ACTUALLY HELPFUL FOR THESE PATIENTS WITH DUCHENNE MUSCULAR DYSTROPHY AND SPINAL MUSCULAR ATROPHY. THERE'S NOT A LOT OF DATA UNLESS YOU GET INTO HIGH RESISTANCE LOADS WITH eCENTRIC CONTRACTION PARADIGMS WE START GETTING DECREASE IN STRENGTH OR ACTUAL ACCELERATION OF FIBER DAMAGE. >> THANK YOU VERY MUCH. THAT WAS A GREAT PRESENTATION. WE ARE WRAPPING UP AND THANK YOU TO ALL THE SPEAKERS WHO HAVE PRESENTED TODAY AND YESTERDAY WE HAD SOME GREAT DISCUSSIONS AND IT'S BEEN REALLY VALUABLE. THANK YOU ALSO TO THE WORK GROUPS CONTINUING TO WORK ON RESEARCH PLAN AND REHABILITATION CONFERENCE, THIS IS A REMINDER TO PUT IN YOUR CALENDAR, OCTOBER 15 AND 16 OF THIS YEAR. I WOULD LIKE TO THANK ALL THOSE WHO HELPED ORGANIZE THIS MEETING AND MAKE SUCH A DIFFERENCE TO MOVING OUR WORK FORWARD TO ALLISON, CONGRATULATIONS AGAIN ON YOUR MOVE, WE LOOK FORWARD TO YOU BEING AN ADVOCATE FOR US. AND TO TIER IS A AND RALPH WE APPRECIATE YOUR LEADERSHIP. THANK YOU. TO ALL BOARD OF DIRECTORS, BOARD MEMBERS ALSO, WE REALLY APPRECIATE ALL THE TIME AND ENERGY YOU PUT INTO THESE MEETINGS. SO JUST AS A REMINDER, THE NEXT MEETING IS MAY 4 AND 5TH, THIS COMING IN 2020, THIS COMING YEAR. AND WE CAN OPEN UP TO DISCUSSION NOW FOR TOPICS COULD LIKE TO HEAR ABOUT FOR THAT MEETING. >> ANY CONVERSATION WE HAVE HAD IN THE LAST DAY AND A HALF YOU WOULD LIKE TO FOLLOW-UP ON OR TAKE A DIFFERENT ADDITIONAL TACK ON? >> I WAS CURIOUS WILL WE BE DOING ADDITIONAL BREAK OUT GROUPS OR ANYTHING AS RELATES TO THE RESEARCH PLAN AND THE CONFERENCE? >> WE WON'T BE DOING THOSE HERE BUT WE WILL BE DOING THOSE SCHEDULING THEM AND DOING THEM PRIOR TO THOSE -- PRIOR TO THAT MEETING FOR SURE. A LOT OF WORK STILL TO BE DONE. >> JUST TO ANSWER THAT QUESTION WE MAY BE ADDRESSING THE PLAN, THE CONFERENCE PROBABLY WILL BE RELATIVELY SET BY THEN. AT LEAST WE HOPE IT WILL BE RELATIVELY SET. ONE QUESTION TO ANSWER BY FRIDAY. THEN WE SHOULD START SENDING OUT INVITES AND STARTING WITH LOGISTICS BECAUSE WE NEED TO GET -- WE ARE BEHIND ALREADY ACTUALLY. >> I DON'T KNOW IF THIS WILL BE A VIABLE TOPIC BUT I'M CURIOUS ABOUT A DISCUSSION TO BUILD ON WHAT RALPH TALKED ABOUT YESTERDAY, THE KO 1 OR R -- K-9 9 R 00 MECHANISMS AND K OTHER K MECHANISMS VERSUS THE PROS AN CONS. THE CONTRAST. IN TALKING TO COLLEAGUES ABOUT WHEN TO ADVISE PEOPLE TO GO FOR K-9 9 VERSUS K 01, THERE'S A DEBATE AS TO THE BENEFITS OF EACH OF THOSE MECHANISMS AND THE AMOUNT OF PROTECTED TIME EACH HAS. I DON'T KNOW IF THAT WOULD BE A TOPIC OF INTEREST TO THE GROUP IN TERMS OF ADVISING MENTEES IN TERMS OF STRATEGIES TO PURSUE. CAN BE A DEBATE OF SORTS TOO. >> I CAN GIVE YOU BACKGROUND ON THE NIH SIDE OF IT AND I THINK WE CAN TALK PARTICULARLY HOW IT PLAYS OUT IN OUR DIFFERENT REHAB CAREER TRAJECTORIES AND WHAT MAKES SENSE. WHAT -- DISCUSSION WHAT BLIND SPOTS WE HAVE AND WHAT WE MIGHT HAVE TO INCENTIVIZE, A INTERESTING FOLLOW-UP TO OUR K 12 DISCUSSION. >> IT'S A QUESTION COMING UP OVER AND OVER AGAIN WITH MENTEES SAYING SHOULD I GO FOR THIS OR THAT AND IT WOULD BE NICE TO HAVE SOME SORT OF SOMETHING MORE CONCRETE IN TERMS OF ADVISING THEM IN TERMS OF GUIDELINE >> CAN I ASK WHAT OTHER DATA IS PART OF THAT DISCUSSION, WHAT ELSE WE SHOULD THINK ABOUT? >> I GUESS MEMBERS OF INDIVIDUALS THAT HAVE GONE K-99 R 00 MECHANISM TIME TO TRANSITION RO1 VERSUS K MECHANISM AND ONE QUESTION THAT COMES UP IS WHEN YOU GO -- DEPENDING BECAUSE THE AMOUNT OF FUNDING IN THE R 00 -- K-9 9 R 00 IF YOU WANT 75% PROTECTED TIME FOR RESEARCH, YOU OFTEN HAVE TO GET A RO1 QUICKLY IN ORDER TO COVER THAT GAP VERSUS A K HAVING -- LONGER PERIOD OF TIME SO MAYBE SOME DATA SHOWING STATISTICS ON WHAT WE HAVE SEEN SO FAR AS FAR AS TIME COURSES TO THOSE TYPES OF TRANSITIONS. OTHER PEOPLE HAVE SUGGESTIONS TO ADD TO THAT. >> I THINK AS WELL AS GOOD CONTROL GROUP FOR EQUIVALENT CAREER PATHS AND HOW PEOPLE HOW LONG IT TAKES TO GET RO1 WHETHER OR NOT YOU HAVE A K. SO I WOULD LOOK AT BIOENGINEERS OTs, PTs, THE M.D.s WOULD BE VERY USEFUL. >> IT'S REALLY, REALLY HARD TO GET THE GOOD CONTROL GROUPS. SOME OF THAT IS TIMING. SO SOME GROUPS HAVE COME OF AGE DURING THE DOUBLING AND THEY TELL ME HOW EASY TO GET THEIR FIRST RO1 AND WE WERE FUNDING AGENT 30th PERCENTILE COMPARED TO THE PEOPLE COMING OF AGE WHEN WE WERE AT THE 9TH PERCENTILE SO WE TRY VERY HARD BUT SOMETIMES THERE AREN'T A LOT OF NUMBERS SO WE CAN LOOK AT THAT BUT IF YOU ARE DISAPPOINTED WITH THE OUTCOME I'M PREPARING YOU FOR THAT NOW. >> TO ADD TO THAT EVEN RISING BUDGETS MAKE A DIFFERENCE. THE OTHER THING IS WHEN YOU DO CHANGES IN POLICY, SO FOR EXAMPLE RIGHT NOW WITH THE LRP AND CHANGE IN THE K SALARY, WE HAVE LOAN REPAYMENT PROGRAM CHANGES IN K SALARY YOU ALSO HAVE DIFFERENCES IN CONTROLS BECAUSE WE START FUNDING FEWER OF THEM BECAUSE WE ARE DEDICATING THE SAME PERCENTAGE OF MONEY BUT WE CAN FUND FEWER BECAUSE WE ARE SPENDING MORE MONEY PER PERSON. SO EVEN WHEN WE HAVE MORE BUDGET YOU HAVE THAT PROBLEM AS WELL. SO YOU ALMOST HAVE TO TIME LINE SOME OF THIS AND THE OTHER PIECE IS IF YOU LOOK -- AND I WILL ACTUALLY SUGGEST TO Y'ALL AND I APOLOGIZE BUT I HAVE TO RUN BACK TO CAMPUS BUT FOLLOW THE OFFICE OF EXTRAMURAL RESEARCH'S BLOG. AND THE REASON THAT I SAY THAT IS MIKE LAWYER DOES A LOT OF DATA ANALYSIS NIH WIDE. AND LOOKS AT SUCCESS FOR RO1s SO EVEN SUCCESS FOR RESEARCH CAREER THERE'S A NUMBER OF STUDIES COMING OUT THE LAST MONTH ABOUT RESILIENCE. SO IF YOU PUT IN ONE APPLICATION AND YOU GIVE UP, OKAY. IF YOU GO THROUGH AND YOU ACTUALLY GET YOUR FIRST ONE YOU ARE MORE LIKELY TO GET SECOND AND THIRD. THEY ALSO LOOK AT THE IMPACT OF POLICIES THEY LOOK AT THE IMPACT OF WHERE YOU ARE LOCATED. SO IF YOU ARE IN AN IDEA STATE NOT GETTING ADS MUCH FUNDING AT THE UNIVERSITIES VERSUS IF YOU ARE AT SOME OF THE BIG SCHOOLS LIKE HARVARD AND STANFORD AND ALL THOSE PLACES YOU ARE SITUATED APPROPRIATELY, SO THAT THEY TEND TO HAVE MECHANISMS TOGETHER. SO THEY LOOK AT ALL THAT SOCIO DEMOGRAPHIC FACTORS,, WHERE YOU ARE TRAINED, I THINK THAT ALSO WILL HELP INFORM THE DISCUSSIONS. IF YOU ARE NOT FAMILIAR WITH THE FACT THEY PUT OUT THAT DATA ON A MONTHLY BASIS. IT IS ACTUALLY REALLY HELPFUL EVEN FOR SOME OF THE DISCUSSIONS YOU ARE TALKING ABOUT WHERE THEY LOOK AT TIME, TIME TO FIRST AWARD. THEY LOOK AT THAT NUMBER OF DIFFERENT PERSPECTIVES. SO THEY HAVE ALL THE PUBLISHED LITERATURE AND THEN THERE LOOK AT IT TOO, IF IT'S A RESPONSE. ALL THE DATA AVAILABLE FOR YOU TO DOWNLOAD IF YOU WANT TO. >> ONCE DIRECT FINDING WAS M.D.s WHO TWO INTO CONSIDERING RESEARCH CAREERS, ARE MORE QUICK TO PUT IN THE ONE APPLICATION AND JUST GIVE UP. YOU COULD SAY IT'S BECAUSE OF THEIR TRAINING OR ATTITUDE OR BECAUSE OF COMPETING CLINICAL CONSTRAINTS BUT THAT'S BEEN A STRIKING PART ABOUT ANALYZING M.D.s VERSUS M.D. Ph.D.s OR Ph.D.s WHO ARE CONSIDERING ACADEMIC RESEARCH GETTING TO NIH GRANTS. NOT SURE IF JENNIFER JACKSON IS DONE WITH THE DATA. I'M WONDERING IF WE CAN HAVE AN UPDATE OF THAT DATA NEXT MEETING BECAUSE THERE WAS REALLY GREAT DATA. >> NOTICE JENNIFER DID FY 18 DATA. NOW. THOUGH FY 19 ENDED THREE MONTHS AGO. I DON'T THINK WE HAVE THE OFFICIAL DATA THEY ARE TALKING FEBRUARY, MARCH. SO THAT MIGHT NOT BE ENOUGH TIME FOR US TO GET PROCESSED FOR YOU IN MAY, THAT'S WHY WE USUALLY DO THOSE DATA DUTCHES ON YOU GUYS IN DECEMBER. >> IS THERE A DIFFERENCE IN TERMS OF SORT OF THE PORTABILITY OR USE FOR THE K-9 9 R 00 FOR FIRST JOB OR TAKING IT TO A NEW JOB? IN TERMS OF OTHER DIFFERENT ASPECTS TO THAT VERSUS A DIFFERENT K AWARD, VERSUS K 23. >> THE K-9 9 R 00 IS MEANT TO BE PORTABLE. YOUR K-9 9 IS SUPPOSED TO BE YOUR POST DOC AND THEN YOU MOVE AND GET YOUR TENURE TRACK JOB SOMEWHERE ELSE WITH YOUR ROO. THE MENTORED Ks ARE NOT RESEARCH GRANTS, THAT I ARE NOT OURS THAT YOU PICK UP AND YOU TAKE WITH YOU'RE PLACES. SO THERE'S MORE CONSIDERATION ABOUT IF SOMEONE WANTS TO LEAVE ARE THEY GOING TO HAVE THE SAME MENTORING, BE ABLE TO CONTINUE THAT PROJECT SOMEWHERE ELSE AND SOMETIMES PROGRAMS THAT HAVE TO MAKE HARD DECISIONS THAT THIS IS NOT GOING TO WORK SOMEWHERE ELSE. THERE IS A MISCONCEPTION THAT Ks ARE AS PORTABLE AS OURS AND HA IS NOT TRUE. >> I DON'T KNOW IF THIS IS WRAPPED INTO THE DISCUSSION, SLIGHTLY DIFFERENT TOPIC BUT YOU MENTIONED LOAN REPAYMENT GRANTS, WOULD IT BE WORTH HAVING MORE INFORMATION. THAT'S A WAY TO TRACK PEOPLE INTO THE WORK FORCE TO IDENTIFY INDIVIDUALS WHO ARE GOOD CANDIDATES FOR LOAN REPAYMENT GRANTS BUT THERE IS NOT A LOT OF PEED BACK APPLY TO CANDIDATES WHO APPLY TO LOAN REPAYMENT FOR LOAN REPAYMENT GRANTS. THERE IS A LITTLE BIT OF -- HELPFUL TO HAVE A LESS BLACKS BOX AND MORE INFORMATION HOW TO GUIDE AND DIRECT INVESTIGATORS >> WE AGREE. WE DON'T GET ASSIGNED THOSE GRANTS, WE ARE NOT PROGRAM OFFICERS ON LOAN REPAYMENT PLANS OR APPLICATIONS. EXCUSE ME. SO WE WILL HAVE TO GET PEOPLE INTO TALK ABOUT THAT SPECIFICALLY. WE DON'T SEE THOSE. IF THERE'S NO FURTHER DISCUSSION WE WILL BE FOLLOWING UP WITH SOME OF YOU LATER TO INVITE YOU TO PRESENT AT THE NEXT MEETING. T SO HOPE Y'ALL HAVE A WONDERFUL HOLIDAYS. SAFE TRAVELS HOME AND THANK YOU AGAIN FOR YOUR CONTRIBUTIONS.