>> GOOD MORNING, EVERYBODY. I'M DELIGHTED TO SEE EVERYBODY HERE. WE'RE IN FOR AN INTERESTING MEETING, I THINK, AND I APPRECIATE YOU ALL BEING HERE. I'M STEVE KATZ, DIRECTOR OF NIAMS, AND AM CHAIR OF THIS COMMITTEE. AS DULY ELECTEDDED BY THIS COMMITTEE. WE'RE GRATEFUL TO THOSE WHO TRAVELED NEAR AND ALSO WHO TRAVELED FROM FAR AWAY. I KNOW GOING EVEN YESTERDAY WAS A REAL CHALLENGE TO GET THROUGH THE AIRPORTS. WE HAVE A FEW PEOPLE ON THE PHONE. DAN PEREZ. DAN? >> GOOD MORNING. >> HI, GOOD MORNING. AND DR. PLAVY MATTAL, I DON'T KNOW WHETHER PLAVY IS ON THE PHONE, THEY ARE JOINING BY PHONE AND WATCHING BY VIDEO. THIS IS BEING VIDEOCAST. >> WEBCAST. >> IT'S WEBCAST. HERE AT THE TABLE WE HAVE REPRESENTATIVES FROM THE THREE MAJOR INSTITUTES THAT -- WHERE WE ROTATE THE LEADERSHIP, THE CHAIR, AND THAT IS ALAN WILLARD, TO MY RIGHT, WHO IS REPRESENTING DR. WALTER KOROSHETZ WHO HAD THIS ON HIS SCHEDULE BUT WAS CALLED AWAY TO REPRESENT THE NIH AT A MEETING IN BRUSSELS, AND WE HAVE OUR NEW DIRECTOR OF THE EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPNT, DR. DEANNA BEEANKI. I HAVE TO ACKNOWLEDGE GLEN NUCKOLLS WHO HAS REALLY DONE THE YEOMAN'S WORK FOR THIS, AND HE WILL ALSO TELL YOU THERE'S SO MANY PEOPLE WHO HELPED PUTTING THIS MEETING TOGETHER AND IN RESPONDING TO OUR VARIOUS REQUESTS. AND MANY THANKS TO ALL THOSE WHO SUGGESTED AGENDA ITEMS. SOME OF THESE AGENDA ITEMS YOU RECOGNIZE WERE DISCUSSED AT OUR LAST MEETING, AS POSSIBLE AGENDA ITEMS. I THINK THE FIRST THING WE SHOULD PROBABLY DO IS GO AROUND THE TABLE, HAVE EVERYONE INTRODUCE THEMSELVES, LATE COMERS WE'LL HAVE INTRODUCED LATER ON AND TELL US WHERE YOU'RE FROM AND IN THE CASE OF DR. BIANKE SHE'LL TELL YOU HER PERSPECTIVE ON MUSCULAR DYSTROPHY. SO LET'S START WITH GLEN. >> GOOD MORNING, GLEN NUCKOLLS, PROGRAM DIRECTOR WITH THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE. >> DIANA BIANKE, NEW DIRECTOR OF NICHD AND A MEDICAL GENETICIST AND NEONATOLIGIST, MY FOURTH WEEK AT NIH AFTER BEING AT TUFTS FOR 23 YEARS. I MENTION TUFTS BECAUSE THE PRESIDENT OF TUFTS UNIVERSITY IS TONY MONACO, AND I WORK ACROSS THE HALL FROM HIM IN THE 1980s WHEN HE DISCOVERED AND DID MY FELLOWSHIP WORK UNDER LOU KUNKLE. AND IF YOU WEREN'T WORKING ON MUSCULAR DYSTROPHY AT THE TIME YOU WEREN'T PART OF THE IN CROWD. WITH MY INTEREST IN MATERNAL FETAL MEDICINE AND NEONATOLOGY, WE DID A PROJECT LOOKING AT THE DELIVERY PERFORMANCE OF WOMEN WHO WERE OBLIGATE CARRIERS OF DMD MUTATIONS, AND IT TURNED OUT VERY INTERESTINGLY, THESE WOMEN HAD A HIGHER INCIDENCE OF BREACH DELIVERIES. WE INITIALLY THOUGHT IT WAS BECAUSE THESE WERE THE AFFECTED BOYS BUT IT TURNED OUT THAT THERE'S A LOT OF DYSTROPHINE IN THE WOMEN WHO WERE CARRIERS OF MUSCULAR DYSTROPHY, RELATED TO THE MOTHER'S PERFORMANCE THAT UTERUS WAS UNABLE TO GIVE SIGNALS TO THE FETUS TO FLIP AROUND AND TURN VERTEX, SO THE WOMEN HAD A FIVE-FOLD HIGHER INCIDENCE OF BREACH DELIVERY AND MUCH HIGHER INCIDENCE OF CESAREAN SECTION. WE THOUGHT THAT WAS QUITE INTERESTING. BEING A GENETICIST, I'M ABSOLUTELY THRILLED AFTER MANY YEARS FOCUSING ON DIAGNOSTIC TESTS THAT MEDICAL GENETICS ARE BECOMING A THERAPEUTIC SPECIALLY, ONE REASON WHY I'M VERY PLEASED AND PRIVILEGED TO PARTICIPATE AND HEAR ABOUT THE ADVANCES IN MUSCULAR DYSTROPHY. >> VALERIE SWIKCER. >> GOOD MORNING, (INDISCERNIBLE) OFFICE OF THE FOOD AND DRUG ADMINISTRATION. >> GOOD MORNING, MELISSA SPENCER WITH YOUR THE OFFICE OF DISABILITY FOR SOCIAL SECURITY, CREATE AND MAINTAIN THE POLICY FOR THE NATION'S DISABILITY PROGRAMS. >> KATHY KINET, SENIOR VICE PRESIDENT FOR MUSCULAR DYSTROPHY. >> KEVIN CAMPBELL, DIRECTOR OF THE IOWA WELLSTONE CENTER, INVESTIGATOR AND CHAIR OF PHYSIOLOGY AT UNIVERSITY OF IOWA. >> KATRINE WAGNER DIRECTOR OF THE CENTER FOR GENETIC MUSCLE DISORDER AND KENNEDY KRIEGER AND PROFESSOR AT JOHNS HOPKINS SCHOOL OF MEDICINE. >> JOHN PORTER, CHIEF SCIENCE OFFICER FOR THE MYOTONIC DYSTROPHY FOUNDATION. >> SKIP NELSON, OFFICE OF THERAPEUTICS AT THE FDA. >> BRANCH CHIEF OF PEDIATRIC PHARMACOLOGY AT NICHD. >> TOM KIEFER, PROGRAM DIRECTOR >> PAT BURLAN. >> WANDA SALTSER. >> SHARON HESTER, BAMBOO PFIZER, I'VE BEEN WITH MDA, PPMD AND MYOTONIC DYSTROPHY FOUNDATION. >> MICHAEL FOX, WITH THE NATIONAL CENTER ON BIRTH DEFECT IT'S AND DEVELOPMENTAL DISABILITIES, THE CDC. >> PETER WANG, ENTERPRISE MEDICAL DIRECTOR AT USA, I'M A POPULATION HEALTH PHYSICIAN, BUT ALSO REPRESENTING THE MYOTONIC COMMUNITY. >> I'M JOAN SCOTT, DEPUTY DIRECTOR FOR CHILDREN WITH SPECIAL HEALTH NEEDS, MATERNITY BUREAU AT HRSA. >> SUE SWANSON, ACTING ASSISTANT SECRETARY OF THE OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES IN THE U.S. DEPARTMENT OF EDUCATION, WE FUND STATES TO PROMOTE SPECIAL EDUCATION AND WE REGULATE THAT AND WE ALSO FUND VOCATIONAL REHABILITATION FOR ADULTS WITH DISABILITIES. I AM THE MOTHER OF THREE MEN, THE MIDDLE OF WHOM HAD A DYSTROPHY DIAGNOSIS, I WAS IN THE PROCESS OF TRYING TO GET HIM CONNECTED TO IOWA UNDER THE ADVICE OF JIM HANSON, WORKED SEVERAL YEARS FOR EUNICE KENNEDY SHRIVER, WORKING FOR HER WHEN SHE HAD THE IDEA TO RENAME THE INSTITUTE, THOUGH IT WASN'T MY IDEA. [LAUGHTER] >> GOOD MORNING, I'M ALAN WILLARD, ACTING DEPUTIY DIRECTOR OF NINDS. WE'RE GOING TO BE TALKING ABOUT CAREER DEVELOPMENT, I WANTED TO ACKNOWLEDGE THE MUSCULAR DYSTROPHY ASSOCIATION FOR HAVING SUPPORTED ME WITH MY FIRST POSTDOCTORAL FELLOWSHIP AT HARVARD IN 1980 AND 81. >> THE PEOPLE AT THE TABLE ARE EITHER MEMBERS OF THE COMMITTEE OR ARE CONTRIBUTING TO TODAY'S MEETING. AND I HOPE YOU GOT A SENSE THAT WE REPRESENT REALLY ALL OF GOVERNMENT, BECAUSE THESE ARE AGENCIES WELL BEYOND THE AGENCY THAT HUMAN AND HEALTH -- HEALTH AND HUMAN SERVICES. FIRST AS THE -- I ALSO WANT TO POINT OUT ONE OTHER PERSON, KATHY SPONG, DEPUTIY DIRECTOR OF NICHD, AND SHE HAS HELPED ME WHEN WE TALKED ABOUT WHAT WILL SORT OF CONFERENCE WE SHOULD HAVE IN THE MORNING IN TERMS OF ETHICAL ASPECTS AND I HOPE, KATHY, YOU'LL CONTRIBUTE. KATHY IS AN OBSTETRICIAN GYNECOLOGIST AND INVESTIGATOR AT NICHD. SO THE MUSCULAR DYSTROPHY COORDINATING COMMITTEE IS ESSENTIAL -- ITS ESSENTIAL TO PROVIDE A FORM FOR MEMBERS TO REPORT ON ACTIVITIES THAT ARE CURRENTLY OUTSIDE THE GROUP. THAT'S ONE PART OF EVERY MEETING THAT WE HAVE. WE CAN'T HEAR ABOUT EVERY MEETING BUT WE'LL HEAR ABOUT SEVERAL MEETINGS THAT OCCURRED SINCE THE COMMITTEE CONVENED IN APRIL. IF YOU KNOW OF WORKSHOPS, CONFERENCES OR INITIATIVES THAT MIGHT BE OF INTEREST LET AGAIN KNOW TO RESERVE TIME FOR UPDATE AT NEXT MEETING. MEETINGS ARE COMMITTED TO HAVING MEETINGS TWICE A YEAR AS OPPOSED TO ONCE A YEAR STARTING LAST YEAR. WE ALSO WELCOME OTHER TYPES OF AGENDA ITEMS. FOR EXAMPLE, THE TOPIC OF ETHICS, PEDIATRIC CLINICAL TRIALS THAT WE'LL BE DISCUSSING TODAY CAME FROM DR. DEV JAPALI OF THE U.S. FOOD AND DRUG ADMINISTRATION, A GREAT WHY THE, VERY APPROPRIATE, AND WE'RE SO HAPPY THAT MISS PAT FURLONG FROM PARENT PROJECT WHO I'VE KNOWN FOR A LONG TIME AND DR. SKIP NELSON AND ANN WILL PRESENT THREE ASPECTS TAKING INTO ACCOUNT WITH CLINICAL STUDIES INVOLVING CHILDREN AND WHAT'S SAID HERE ABOUT MUSCULAR DYSTROPHY RELATES TO MANY, MANY, MANY OF THE RARE DISEASES AND WHAT PAT SENT AROUND, I DON'T KNOW WHETHER YOU SENT IT TO EVERYONE, A SERIES OF PAPERS THAT IS GERMANE, THOSE ISSUES ARE GERMANE TO BASICALLY ALL RARE DISEASES. IN FOLLOW-UP TO APRIL, WE APPRECIATE THE EFFORTS OF DR. VALERIE SERWICK OF THE MDA AND GLEN NUCKOLLS AND I BELIEVE WE'VE RESERVED TIME DURING LUNCH FOR YOU ALL TO GET TOGETHER AND COME BACK AND REPORT TO THE GROUP AFTER OUR LUNCH TIME BREAK. SO THANK YOU VERY MUCH FOR DOING THAT. OUR FINAL TOPIC BUILDS UPON THE TOPIC FROM THE APRIL MEETING, THOSE HERE WILL REMEMBER THAT GLEN NUCKOLLS AND HEATHER REESE -- I DON'T KNOW IF HEATHER IS HERE -- PRESENTED A VERY INTERESTING DATA FROM THE NIH WITH REGARD TO THE FUTURE, THOSE IN TRAINING, AND THOSE WHO ARE GETTING EARLY AWARDS AND THOSE GETTING RO1 AWARDS FROM THE MUSCULAR DYSTROPHY COMMUNITY, AND THERE WAS SOME CONCERN EXPRESSED BY ME AND OTHERS WITH REGARD TO THE FUTURE AND HOW YOU GET PEOPLE INTO THE AREA OF MUSCULAR DYSTROPHY RESEARCH, BECAUSE IF YOU DO IT EARLY, YOU GET THERE EARLY. AND YOU GET PEOPLE HOOKED. SO WE HAVE INVITED DR. WAGNER. WE'VE INVITED -- OF THE KENNEDY KRIEGER INSTITUTE AND DR. CAMPBELL FROM THE UNIVERSITY OF IOWA TO DESCRIBE SOME ISSUES FACING NEW INVESTIGATORS WHO WISH TO STUDY MUSCULAR DYSTROPHIES. THEN TOM KIEFER AND GLEN NUCKOLLS WILL PRESENT SOME DATA FROM THE NIH WHICH WE HOPE WILL SERVE AS A BASIS FOR DISCUSSION ABOUT HOW FUNDING ORGANIZATIONS INCLUDING BUT NOT LIMITED TO NIH CAN FURTHER ATTRACT AND RETAIN TALENTED RESEARCHERS AND PROMOTE THEIR SUCCESS AND WE'LL TALK ABOUT SOME OF THE LEVERAGING THAT GOES ON IN OTHER INSTITUTES WITH PROFESSIONAL AND VOLUNTARY ORGANIZATIONS, REALLY BEST CASE SCENARIO. AND THE WRAP-UP IS I LOOK FORWARD TO THE MANY INTERESTING PRESENTATIONS AND DISCUSSIONS. THEN WE CAN -- WE'LL WRAP UP PROBABLY AT 4:00, AND SO THAT WE CAN BEGIN, BUT JUST BEFORE WE BEGIN I WANT JIM TO INTRODUCE HIMSELF. >> GOOD MORNING, JIM KYLIE, DIRECTOR OF DISEASES, NATIONAL HEART LUNG BLOOD INSTITUTE. >> I'LL ASK GLEN NUCKOLLS TO REVIEW THE NECESSARY INFORMATION. >> THIS MEETING IS BEING CONDUCTED UNDER THE POLICIES OF THE FEDERAL ADVISORY COMMITTEE ACT, SO THE NON-FEDERAL MEMBERS OF THE COMMITTEE WHEN YOU CAME IN THERE SHOULD HAVE BEEN A PACKET THAT IS ABOUT YOUR POTENTIAL CONFLICTS OF INTEREST, ALTHOUGH THERE'S NO ACTUAL PLACE TO SIGN THAT, PLEASE SIGN THAT DOCUMENT, AND RETURN IT TO LIZ SOMETIME TODAY. IT WILL KEEP THAT ON RECORD. SO WE DON'T PLAN TO HAVE A CLOSED SESSION FOR THIS MEETING, AND WE DON'T PLAN TO VOTE ON ANY ACTIONS SO IF THOSE PLANS CHANGE DURING THE MEETING THEN WE'LL TAKE THE DECLARED AND APPARENT CONFLICTS OF INTEREST INTO CONSIDERATION AND RECUSE CONFLICTED PARTIES FROM THE DELIBERATION AND VOTING. AS IS CUSTOMARY FOR THIS MEETING, WE POST A NOTICE OF THE MEETING IN THE FEDERAL REGISTER, AND INVITE PUBLIC COMMENT. WE DID NOT RECEIVE ANY REQUESTS TO MAKE PUBLIC COMMENTS AT THIS MEETING SO TIME WAS NOT ALLOCATED ON THE AGENDA FOR THAT. IF ANYONE FROM THE PUBLIC WOULD LIKE TO MAKE COMMENTS TO THE COMMITTEE, PLEASE LET ME KNOW BY THE END OF LUNCH TIME AND WE'LL SCHEDULE THAT FOR THE END OF THE MEETING. SO I'D REALLY LIKE TO ACKNOWLEDGE THE OTHER NIH STAFF THAT HELPED PREPARE FOR THESE MEETINGS OF THIS COMMITTEE, SO ASHLEY VANT, COULD YOU STAND PLEASE? SHE'S BEEN A PROGRAM ANALYST CAN WITH NINDS FOR TWO YEARS AND HAS DONE EVERYTHING FROM HELP TO EDIT THE ACTION PLAN TO CO-AUTHORING OUR PUBLICATION AND MANAGING THE REGISTRATION SITE, AND RUNNING THE WEBEX CONNECTION, SO ASHLEY AS GRADUATED FROM NINDS, SO TO SPEAK, NOW A PROGRAM DIRECTOR WITH THE NATIONAL INSTITUTE OF MENTAL HEALTH AND SHE WILL NO LONGER BE INVOLVED IN MDCC AND I'D LIKE TO THANK ASHLEY FOR HER HELP. [APPLAUSE] >> LET ME ADD MY APPRECIATION, ASHLEY. YOU'VE BEEN IN ALL THE MEETINGS. >> AND EMILY IS A NEW PROGRAM ANALYST WITH NINDS, TAKING OVER MANY OF THE RESPONSIBILITIES THAT ASHLEY'S HAD. I'D LIKE TO THANK HEARD REEF AND TOM AND JOHNEL FOR THEIR HELP AND LIZ CORTI AT THE REGISTRATION TABLE FOR HER HELP IN PREPARING FOR THIS MEETING. FOR THOSE OF YOU WHO PRE-ORDERED LUNCHES WE EXPECT THEM TO BE DELIVERED JUST BEFORE NOON. IF YOU DID NOT ORDER LUNCH THERE'S STILL A COUPLE OPTIONS SO THERE'S A SNACK SHOP DIAGONALLY ACROSS THE LOBBY, A LIMITED SELECTION BUT THERE'S SOMETHING THERE AND IF THERE'S TIME THERE'S ALSO A DELI IN THE FRONT SIDE OF THE BUILDING THAT'S KIND OF JUST THAT WAY FROM HERE, SO IF YOU GO OUT THE FRONT DOOR OF THE BUILDING AND TURN TO THE RIGHT. AND THE RESTROOMS ARE BEHIND THE SECURITY DESK IN THE LOBBY WHERE YOU CAME IN. SO UNLESS THERE ARE OTHER QUESTIONS, I'LL GIVE IT BACK TO STEVE TO START THE SESSION. >> OKAY. WELL, THANKS VERY MUCH. AS I SAID, WE LIKE TO START OUR MEETINGS, SOMETIMES WE END THE MEETINGS, TODAY WE DECIDED TO START OUR MEETINGS WITH SOME BRIEF REPORTS OF MEETINGS THAT HAD TAKEN PLACE, WE'RE GOING TO START WITH DAN PEREZ PRESENTING REMOTELY FROM THE FSH SOCIETY. SO, DAN, YOU'RE ON. THANK YOU VERY MUCH FOR YOUR PARTICIPATION. >> OKAY. I'LL TRYING TO FIGURE OUT HOW I PRESENT HERE. >> YOU SHOULD BE ABLE TO SEE IF YOU CAN MOVE THE SLIDES. >> IF YOU CAN'T MOVE THE SLIDES WE CAN MOVE THE SLIDES FOR YOU. AND JUST TELL US. >> YOU TAKE CONTROL I'LL SAY NEXT SLIDE. >> THAT'S FINE. >> I FORGET WHETHER WE ARE. SORRY. THERE WE ARE, OKAY. OKAY. THANK YOU. SO THANK YOU FOR HAVING ME. I'M DAN PEREZ, I'M CEO OF THE FSH SOCIETY AND ALSO A NON-FEDERAL AGENCY MEMBER OF THE MDCC ASKED TO SPEAK ABOUT AN ANNUAL MEETING THAT THE SOCIETY RUNS EVERY YEAR CALLED THE FSHD INTERNATIONAL RESEARCH CONSORTIUM. NEXT SLIDE PLEASE. SO EACH YEAR WE HAVE RESEARCH AND CLINICAL COMMUNITY WITH SOME ROLE, ALL STAKEHOLDERS IN ONE LOCATION, AND THIS IS THE RESEARCHERS, CLINICIANS, INDUSTRY, AND YOU CAN SEE THESE ARE THE SPONSORS FOR THIS YEAR INCLUDING FUNDING AGENCIES MDA, UK SOCIETY, NIH AS WELL, THE WELLSTONE. NEXT SLIDE. THE ORGANIZER FOR THIS MEETING, DAVID HOUSEMAN, CHAIR OF THE SOCIETY ADVISORY BOARD AND (INDISCERNIBLE) I KNOW WELL THROUGH PARTICIPATION IN WELLSTONE PROJECT PROGRAM AND OTHER NIH-FUNDED RESEARCH, STEVE SCOTT, PHIL, KATHERINE WAGNER, AND I MYSELF PRINCIPALLY THE ORGANIZER OF THE MEETING. NEXT SLIDE. SO BASICALLY THIS IS SMALL BUT BASICALLY WHAT WE DO IS EACH YEAR WE ASK THE COMMUNITY, ABSTRACTS, WE GO OUT TO FOUR OR FIVE HUNDRED RESEARCHERS NOW AND INDUSTRY INTERESTED IN FSHD, THIS YEAR RECEIVED 50 ABSTRACTS, WHAT WE DO IS HAVE ONE DAY, A DAY AND A HALF MEETING, ONE DAY IS FOR PRESENTATIONS ONLY, AND THE SECOND DAY IS FOR DISCUSSION. SO OUT OF THE 50 ABSTRACTS THAT WE RECEIVED, WE DECIDED ON 23 PLATFORMS, PRESENTATIONS, AND 26 POSTERS, AND THOSE ARE ROUGHLY BROKEN INTO FOUR DIFFERENT AREAS, CLINICAL STUDIES, GENETICS, EPIGENETICS, AND YOU CAN SEE VARIOUS TOPICS HERE, CONGENITAL (INDISCERNIBLE) AND GENE MODIFIERS. NEXT SLIDE. NEXT SLIDE. BASICALLY SOMEDAY DAY ONE A REVIEW OF THE 2015-16 PRIORITIES. WE ASK RESEARCHERS TO STATE PRIORITIES FOR THE UPCOMING END OF THE YEARS, THE NEXT YEAR, AND POST ON THE WEBSITE. WE HAVE FOUR PLATFORM SESSIONS OF INVENTIONS, CLINICAL STUDIES MODERATED BY DR. TAWIL, WAGNER, WELL KNOWN NAMES IN THE INDUSTRY, SCOTT HARPER, MICHAEL KYBA, YI-WEN CHEN, LOUIS KUNKLE, AND LOU KUNKLE IS CO-DIRECTOR OF THE U-MASS WELLSTONE AND KATHERINE IS PART OF THE WELLSTONE AND THE SEATTLE WELL STONE WORKING ON FSHD. NEXT SLIDE. DAY TWO WE HAVE AN INTERNATIONAL LAB MEETING AND GET 130 PEOPLE, WE HAD 130 ATTENDEES THIS YEAR, A LOT OF PRESENCE FROM INDUSTRY, AND WE BASICALLY SORT OF TALK FOR TWO OR THREE HOURS ON THE RESEARCH TO SORT OF OPEN AND CANDID DISCUSSION AND TRY TO DEFINE PRIORITIES GOING FORWARD. NEXT SLIDE. SO THIS PRESENTATION DOESN'T DO MEETING JUSTICE. THE FIELD IS VERY FAST FORWARD MOVING, LOTS OF GREAT THINGS HAPPENING WITH INDUSTRY, NEW MODELS ARE COMING OUT, NEW CELL MODEL, NEW ANIMAL MODELS, NEW DISCOVERIES, AND RESOURCES, BUT BASICALLY I'LL GIVE YOU THE HIGH LEVEL PRIORITI, AND THESE WILL BE FLESHED OUT OVER THE NEXT COUPLE WEEKS WITH THE ORGANIZERS OF THE MEETING, SORTS OF A VIEW OF WHAT THE PRIORITIES WERE IN THE FOUR AREAS AND I'LL MOVE ALONG BECAUSE I DON'T HAVE THAT MUCH TIME. BUT IN TERMS OF CLINICAL STUDIES, IN THAT AREA THERE WERE BASICALLY FOUR OR FIVE PRIORITIES THAT WERE INDICATED AS NEEDING EMPHASIS AND FUNDING FOR THIS YEAR OR MEETINGS. SO THE FIRST ONE IS NEED FOR SURROGATE OUTCOME BIOMARKERS, AND THAT WAS CONSIDERED OF THE GREATEST NEED. THE SECOND WAS NEED FOR VALIDATED OUTCOME MEASURES, AND THEN THE THIRD WAS ADDITIONAL NATURAL HISTORY STUDIES ARE REQUIRED. AND BASICALLY A LOT OF DISCUSSION WITH INDUSTRY AND CLINICIANS ON HOW WE'RE GOING TO CRACK -- HOW WE'RE GOING TO TEST DRUGS, CRACK THE DRUGS, HOW WE'RE GOING TO MEASURE AND GET AT THE ROOT OF WHAT'S GOING ON IN FSHD, AND THEN THE OTHER AREA WITH INDIVIDUAL AND COOPERATIVE STUDIES TO IDENTIFY, VALIDATE AND DETERMINE BEST STANDARD, THAT'S CRITICAL FOR TRIALS FHSD. THROUGH DISCUSSION ON THE NATURAL HISTORY OF THE DISEASE, EXPERIENCE OF PATIENTS, WE REALLY NEED TO GET DATA, WE'LL HEAR A LOT OF THIS TODAY IN LATER DISCUSSIONS, AND WE REALLY NEED TO DO -- NEED TO CAPTURE THE DATA EFFECTIVELY. NEXT SLIDE. SO THE SECOND MAIN AREA WITH GENETICS AND EPIGENETICS AND WE NEED TO STRATIFY GENOTYPE FORMATION, GETTING MORE AND MORE INVOLVED AND IT'S BREAKING OUT VARIOUS SUBGROUPS OR SUBPOPULATIONS OF THE DISEASE, REALLY IMPORTANT IN TERMS OF CLINICAL TRIALS, SO UNIFORMITY IN GENETIC TESTING AND SUBGROUPING IS A KEY ISSUE. WE NEED TO FURTHER UNDERSTAND EPIGENETIC REGULATION TO UNDERSTAND THE DISEASE PROCESS AND THE DISEASE MECHANISM. WE SUGGESTED THAT THESE TWO PRIORITIES THAT WE HAVE A SUBMEETING IN THE NEXT SEVEN OR EIGHT MONTHS AND ESTABLISH A CENTRAL BODY OR EQUIVALENT SUCH AS WORLD ANTI-DOPING AUTHORITY FOR THE OLYMPICS SO THAT TO ACCESS OR DEFINE UNIFORMITY AND GENETIC TESTING AND FIGURE OUT HOW THE WORLD-WIDE -- GET A WORLDWIDE VIEW OF UNIFORMITY AND GENETIC TESTING. OTHER AREAS CONSIDERED CONTINUED PRIORITY, MODIFIERS OF DISEASE MECHANIC AND MEASURES. PRIORITY ONE WAS NEED TO UNDERSTAND GENETIC TOXICITY AND EFFICACY, UNDERSTAND DUX4 RNA PROTEIN, HOW TO SILENCE IT AND SILENCE RNA. THE QUESTION OF DUX4 IS PROBABLY EFFECTIVITY IN THE NUCLEUS TO THE BINDING OF DNA POSSIBLY TO TRANSCRIPTIONAL ACTIVITIENED AND IF WE KNOW HOW TO EPIGENETICALLY SCIENCE IT, SILENCE RNA, WE CAN SILENCE THE ACTIVITY, THAT'S A GOOD PROCESS. HOWEVER, IT'S THOUGHT THE NEED TO UNDERSTAND WHAT THE REAL PATHOPHYSIOLOGY IS OF FSHD IS A HUGE PRIORITY. WE UNDERSTAND GENETICALLY WHAT'S AT THE BASIS, WHAT WE DON'T UNDERSTAND WHAT IT DOES AND HOW IT KILLS MUSCLE. SO REMAINS WHILE THE EFFORT TO SILENCE DUX4 IS ONGOING, AND BIG BLACK BOX IN TERMS OF WHAT THE REAL PATHOPHYSIOLOGY IS, THIS BOX INTELLECTUALLY NEEDS TO BE FILLED IN, MAY NOT NEED TO BE FILLED IN IN ORDER FOR US TO CONTINUE TO DEVELOP THERAPIES NOW AND ONGOING BASIS. NEXT SLIDE. WE NEED TO ALSO REFINE THE RELATIONSHIP TO OTHER MARKERS AND CORRELATION BETWEEN THE QUESTION AND ACTIVITY, TRANSCRIPTIONAL ACTIVITY OF DUX4 WITH CURRENT MARKERS WE HAVE, SOME WERE ESSENTIALLY MARKERS OF CORRELATE, DISEASE MUSCLE, MRI CORE CORRELATES AND HOW DO WE MEASURE DISEASE PROGRESSION IN SHORT TIME WINDOWS IF FOCUSED TO A SPECIFIC MARKER AND SPECIFIC MUSCLE GROUP, SO THESE ARE ALL OF INTEREST. NEXT SLIDE. SO IN MODELS IT WAS THOUGHT WE NEED TO CREATE A FOCUS THAT WE'RE MEASURING THE SAME KINDS OF THINGS AND THAT WE TRANSLATE MODELS INTO A USABLE TOOL FOR OUR THERAPEUTIC INDUSTRY. IT'S THOUGHT THAT WE HAVE PROBABLY 20 OR 30 DIFFERENT KINDS OF MODELS, MODELS NOW REALLY WELL UTILIZED AND COMING INTO BEING, SO IT'S THOUGHT WE NEED TO ESTABLISH A MEETING, CONSORTIUM, OF LABORATORIES THAT ARE WORKING ON MOUSE AND ANIMAL MODELS, IT WAS SUGGESTED COMMERCIAL ENTITIES, DRUG COMPANIES AND BIOPHARMA THAT ARE ATTEMPTING TO ENTER THE THERAPEUTIC BASE SHOULD BE INVOLVED IN THESE MEETINGS AND THIS WOULD IN A WAY HELP ACCELERATE AND LOWER THE RISK OF THE ANIMAL MODELS, EVERYBODY'S IN THE SAME ROOM TALKING ABOUT THE MODELS AND HOW TO USE THE MODELS. THIS WAS A LARGE COMPONENT OF THE MEETING THIS YEAR, THIS DISCUSSION. SO IN TERMS OF PRIORITIES, THERE'S A NEED FOR FURTHER DEVELOPMENT, CHARACTERIZATION AND USE OF ANIMAL MODELS. THE WHOLE ANIMAL, MICE, FISH, PIG AND MAMMAL. XENOGRAFT MODELS, TRANSPLANTATION OR CELL ENGRAFTMENT AND NEED FOR REAL HUMAN MUSCLE ACCESS AS WELL, AND THEN THAT WAS THOUGHT WE NEED MORE EMPHASIS ON CELLULAR MODELS AND ALL ASPECTS OF MODELS. NEXT SLIDE. THERE'S A LOT OF DISCUSSION ON MODELS THAT NEED TO EITHER GO AFTER HYPOTHESIS OR RECAPITULATE DISEASE AND PROGRESSION AND WE NEED MODELS TO HELP DEVELOP PRECISELY HOW WE DELIVER FORMULATE AND GET CONCEPTUAL ENTITY TO DISSECT THE THERAPEUTIC VIEW OF THE REQUIREMENT, SOMETHING WE NEED AND CAN TEST. AND WE NEED TO ADDRESS THE FORMULATION AND DELIVERY ISSUES AND HALF-LIFE ISSUE OF PK, PD, ET CETERA. IT WAS THOUGHT WE SHOULD DO THIS NOT ONLY IN NORMAL MODELS BUT NEED TO ALSO UNDERSTAND WHAT HAPPENS TO THESE IN THE DISEASE ORGANISM AND LESSONS LEARNED FROM DUCHENNE SHOULD BE CONSIDERED IN THIS ASPECT. NEXT SLIDE. THAT'S IT FOR NOW. I JUST WANTED TO SAY THERE WAS A LOT OF GREAT DISCUSSION. GO FORWARD PLEASE. THERE WAS A LOT OF DISCUSSION. NO, GO BACK ONE. THANK YOU. THERE WAS A LOT OF DISCUSSION OF MODELS USED, CHARACTERIZATION AND AVAILABILITY. I DID WANT TO DO A SHOUT OUT THE DUX4, FLEX DUX4 IS COMMERCIALLY AVAILABLE, NIH CONTINUED FUNDING FOR NOW A (INDISCERNIBLE) MODEL, AVAILABLE AT JACKSON FOR FSH AND WE'RE ALSO SHORTLY TRYING TO MAKE AVAILABLE LARGE COHORTS AT CORIELL, 120 CELL LINES ACROSS 12 MULTI-GENERATION FAMILIES. NEXT SLIDE. AND THEN AS ALWAYS WE GET INFORMATION IN A MORE COGENT FORM, WE HAVE PARTICIPATED IN DISCUSSION, WEEKS TO SYNTHESIZE CAN ORGANIZERS, POSTED ON THE FSHD WEBSITE UNDER THE INTERNATIONAL RESEARCH CONSORTIUM. CURRENTLY YOU CAN FIND THE 70 PAGE PROGRAM ON THERE, AND THEN THE FINAL PRIORITY DOCUMENT ONCE THE CO-CHAIRS HAVE FINALIZED THE PARTICULAR SET OF WRITINGS. SO THAT'S MY PRESENTATION FOR NOW, AND I'LL TAKE ANY QUESTIONS IF YOU'D LIKE FOR ME TO TAKE QUESTIONS AT THIS TIME. >> I THINK WHAT WE'RE GOING TO DO, DAN, IS WE'RE GOING TO GO THROUGH EACH OF THE MEETING REPORTS AND WE'LL COME BACK WITH SPECIFIC QUESTIONS. DAN, WE ALSO LOOK FORWARD TO YOUR PARTICIPATION IN OUR LONGER TERM DISCUSSION THIS MORNING AND AS WELL AS THIS AFTERNOON IN TERMS OF TRAINING THE FUTURE INVESTIGATORS IN MUSCULAR DYSTROPHY. THANK YOU VERY MUCH FOR THAT INTERESTING PRESENTATION. SOUNDS LIKE A VERY, VERY FRUITFUL MEETING. NEXT WE'RE GOING TO HEAR FROM KATHY KINET FROM THE PARENTS PROJECT MUSCULAR DYSTROPHY ON THE MEETING ON BONE HEALTH AND OSTEOPOROSIS IN DUCHENNE MUSCULAR DYSTROPHY. >> HI. ONE OF THE TASKS OF PPMD HAS BEEN TO IDENTIFY GAPS IN BOTH RESEARCH AND CARE THROUGH OUR ORGANIZATION THROUGH THE CERTIFIED DUCHENNE CARE CENTER NETWORK. ONE AREA OF HUGE DISCREPANCY HAS BEEN OSTEOPOROSIS AND BONE HEALTH. SO -- UH-OH. IN MAY OF 2016 WE HELD A MEETING IN BETHESDA. THE PURPOSE, THE BACKGROUND, BONE HEALTH IN PEDIATRICS IS COMPLICATED AND CONFUSING AND BONE HEALTH AND DUCHENNE IS MORE SO. A HUGE VARIABILITY IN CLINICAL MANAGEMENT, AND MOST OF THIS IS DUE TO A PAUCITY OF RESEARCH. THE GOALS OF THE MEETING WERE TO REVIEW BONE MORBIDITY DUE TO OSTEOPOROSIS IN DUCHENNE, REVIEW CURRENT MANAGEMENT, DISCUSS NON-MECHANISMS OF BONE DISEASE AND PROVIDE RECOMMENDATIONS REGARDING AND DIRECTION FOR FUTURE RESEARCH WITH FOCUS ON DUCHENNE. SO WHEN WE STARTED DISCUSSING OSTEOPOROSIS, AS WE KNOW OSTEOPOROSIS IN MATURE SKELETON IS DUE TO BONE LOSS. THE BONE LOSS OCCURS DUE TO THE EXPANSION OF MEDULLARY CAVITY WHICH IS IN THE MIDDLE OF THE BONE, AND THIS IS MOST OFTEN TREATED BY ANTI-REABSORBATIVE THERAPY. HAVE YOU OSTEOCYTES AND OSTEOBLASTS THAT CONTINUE TO BONE FORMATION AND AT THE MARGIN OF THE COMPACT BONE AND MEDULLARY CAVITY WHICH CONTRIBUTES DO REABSORPTION. IF YOU CAN CONTROL REABSORPTION, CAN YOU CONTINUE TO LAY DOWN NEW BONE AND PREVENT OSTEOPOROSIS IN A MATURE SKELETON. THIS IS DIFFERENT THAN DYSTROPHINOPATHY. YOU HAVE A LACK OF MECHANICAL STIMULATION ON A GROWING SKELETON, AND WITH THAT LACK OF MECHANICAL STIMULATION, YOU HAVE A LACK OF BONE LAID DOWN WHICH RESULTS IN INADEQUATE BONE GAIN. THIS RESULTS IN THINNER BONE SHAFT, YOU HAVE LENGTH OF BONE, A THINNER SHAFT, MUCH MORE FRAGILE. WE FEEL THIS IS BEST TREATED BY STIMULATING BOTH FORMATION ON THE INTERNAL SURFACE OR ENDOOSTEAL OR EXTERNAL BONE SURFACES. GLUCOCORTICOIDS RESULT IN BONE DENSITY, SECONDARILY DECREASING FORMATION OF NEW BONE, AND THEN RESULTING IN PREMATURE DEATH OF OSTEOCYTES WHICH ELIMINATES THE LAYING DOWN MUCH NEW BONE WITHIN THE COMPACT BONE LAYER. IN ADDITION, THE MUSCLE WEAKNESS CONTRIBUTES TO INCREASED FALL OR DECREASED BALANCE AND INCREASED FALL, NOT BENEFICIAL FOR THE SKELETON. ONE OF THE POTENTIAL PATHWAYS THAT WE DISCUSSED IN TERMS OF BONE HEALTH IS THE WNT SIGNALING PATHWAY THAT ACTIVATES BONE FORMATION, NORMALLY IT ENHANCES BONE FORMATION, IN AN ANABOLIC ROLE BUT SWITCHES TO CATABOLIC ROLE IN A MUSCLE-SPARING AND MORE OF A MUSCLE-SPARING ROLE IN GLUCOCORTICOID ACCESS. WITH STEROIDS TREATED, THAT TREAT DUCHENNE, THIS WILL SPARE MUSCLE BUT ALSO IN THE FACE OF GLUCOCORTICOID ACCESS DID NOT ELIMINATE MUSCLE ATROPHY A RESULTED OF MUSCULAR DYSTROPHY, MORE RESEARCH COULD BE DONE. MUSCLE BONE CROSS-TALK WAS DISCUSSED. WE KNOW THERE'S BIOCHEMICAL SIGNALING FROM BONE OR FROM MUSCLE TO BONE, OSTEOCYTES ACCELERATE MYOGENESIS IN FORMATION OF NEW MUSCLE IN NEW MICE, DEFECTIVE WITH AGE, SO AS MICE AGE THERE'S A DECREASE IN MUSCLE THAT'S FORMED. THERE ARE 2004 POTENTIAL OSTEOCYTE FACTORS THAT MAY MEDIATE SIGNALING, PGE2 AND WNT3A INCREASED CONTRACTILE FORCE IN MOUSE MUSCLE, SECRETING BAIBA, MAY BE A NOVEL PATHWAY FOR BONE HEALTH IN DUCHENNE. IN ADDITION THERE'S BONE MUSCLE CROSS-TALK, OSTEOCYTES PRODUCE A FACTOR THAT REDUCES MUSCLE MASS WITH AGING, WE ALSO KNOW THE OSTEOCALCIN IS PRODUCED BY OSTEOBLASTS, PREMATURE BONE CELLS, PROMOTING MUSCLE MASS, BOTH DEMONSTRATE THE BONE REGULATES MUSCLE MASS DURING GROWTH IN AGING. MANY PATHWAYS WE HAVEN'T REALLY INVESTIGATED YET. 20 TO 60% OF BOYS WITH DUCHENNE HAVE LOW TRAUMA FRACTURES, USUALLY TIB/FIB, 30% DEVELOP VERTEBRAL FRACTURES, INCREASE IN BACK PAIN, SPINAL DEFORMITY, PREMATURE AND PERMANENT LOSS OF AMBULATION, RISK OF DEATH DUE TO FAT EMBOLI WHICH CAN RESULT FROM LONG BONE FRACTURE. BISPHOSPHONATES ARE USED, ANTI-REABSORPTION AGENTS, IF WE HAVE INCREASE IN BONE FORMATION WE CAN HAVE INCREASED CORTICO THICKNESS, INCREASE IN TRABECULAR BONE, BISPHOSPHONATES ARE FAIRLY SAFE IN POSTMENOPAUSAL WOMEN, NOT MUCH RESEARCH IN DUCHENNE. SIDE EFFECTS INCLUDE FEVER, BONE PAIN, MYALGIA, NAUSEA AND VOMITING MOST OFTEN SEEN WITH FIRST INFUSION, AGAIN THESE ARE INFUSION AGENTS, SO THEY ARE DIFFICULT SOMEWHAT TO OBTAIN AND PROVIDE. THERE ARE MANY CONTROVERSIES AROUND BISPHOSPHONATES, OPTIMAL AGE AND DOSE, OPTIMAL DURATION OF TREATMENT, SO ALL THOSE THINGS CONTINUE TO BE IN DISCUSSION. THERE AREN'T -- THERE'S NOT EVIDENCE -- HAS NOT BEEN EVIDENCE OF IN JAW NECROSIS IN PEDIATRICS, ATYPICAL FRACTURE MOST DUE TO SUPPRESSION OF BONE TURNOVER HAVE BEEN SEEN IN DUCHENNE. RECOMMENDATIONS ARE ALLS OF BISPHOSPHONATES IN THE LOWEST EFFECTIVE DOSE TO CONTINUE UNTIL ADULT HEIGHT IS REACHED AND GOAL OF THERAPY, CONTINUED THERAPY, AVOID FRACTURE AT JUNCTION TREATED AND NEWLY ADDED BONE. THERE HAVE NOT BEEN STUDIES THAT HAVE INDICATED BISPHOSPHONATES ARE BENEFICIAL IN PRIMARY PREVENTION OR PREVENTION OF FIRST EVER FRACTURES, IN DUCHENNE THERE'S BEEN STUDIES PERFORMED IN O I THAT DEMONSTRATED A POSITIVE IMPACT OF BISPHOSPHONATES ON BONE FRAGILITY, COULD BE PROTECTIVE FOR PREVENTION OF SECONDARY FRACTURES IN DUCHENNE. THERE ARE MEDICATIONS BEING USED RIGHT NOW IN ADULTS THAN NON-BISPHOSPHONATES, TERIPARATIDE SHOWN TO BE MORE EFFECTIVE IN INCREASING BONE MINERAL DENSITY AND REDUCING FRACTURES IN POSTMENOPAUSAL WOMEN, DENOSUMAB BINDS TO RANK ON OSTEOCLASTS, INHIBITS REABSORPTION, IN TRIAL IN GLUCOCORTICOIDS, IN DUCHENNE AT THIS MOMENT. COMBINATION THERAPY HAVE BEEN SHOWN TO INCREASE EFFECTIVENESS. ROMOSOZUMAB ACTIVATES WNT, SHOWN TO INCREASE BONE MINERAL DENSITY GREATER THAN BISPHOSPHONATES OR TERIPARATIDE. IN PEDIATRICS DEMONSTRATED TO BE EFFECTIVE IN OI, SIMILAR EFFECT ON GROWING CELL TIN THAN BISPHOSPHONATES, ADVANTAGE OF DENOSUMAB, MORE EASILY SUPPLIED, SUBCU, EASIER FOR PARENTS AND PATIENTS TO ACCESSES, BETTER CONTROL OF DURATION OF ANTI-REABSORPTION OF AGENT WITH A SHORTER ACTION. DOES HAVE A SIGNIFICANT SIDE EFFECT WHICH IS POTENTIAL FOR SEVERE REBOUND HYPER CALCEMIA, IT HAS TO BE USED WITH GREAT CAUTION. SCLEROSTIN INHIBITION INHIBITS WNT PATHWAY, ANOTHER POTENTIAL THAT NEEDS INVESTIGATION. TERITIDE, BLACK BOX WARNING TO DEVELOP OSTEOSARCOMA IN GROWING PATIENTS, SOY NOT AN OPTION. WE DID DISCUSS NOVEL THERAPIES, STEROID ALTERNATIVES NF-KAPPAB INHIBITORS, MAY BE FOUND TO HAVE BETTER SIDE EFFECT PROFILES THAN GLUCOCORTICOIDS, CONTINUE TO BE IN INVESTIGATION. EXERCISE IS BENEFICIAL TO BONE, DIFFICULT IN DUCHENNE, STUDIES SHOW BODY VIBRATION AT 8 WEEKS WAS NOT BENEFICIAL TIBIAL BONE STRENGTH, BODY VIBRATION AT SIX MONTHS DID DEMONSTRATE SOME BONE STRENGTH IN GEOMETRY, SO FURTHER INVESTIGATION IN EXERCISE ESPECIALLY TARGETING FRACTURE PRONE REGIONS WOULD BE IMPORTANT TO DO. ALL OF THE -- THE CDC IS UPDATING CARE GUIDELINES FOR DUCHENNE, FOCUS ON BONE HEALTH, ON EARLIEST IDENTIFICATION OF BONE FRAGILITY. IN THE PAST DEXA SCANS HAVE BEEN USED TO EVALUATE BONE MINERAL DENSITY AND TREAT BY VIRTUE OF THAT SCORE AND IMPROVE THAT SCORE. DEXAs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s HAD BEEN A TEACHER, SHE HELPED US A LOT IN TERMS OF SETTING UP STATIONS AND EXPLAINING SOME BASIC TECHNIQUES, JUST LIKE PIPETTING AND LETTING THE KIDS, YOU KNOW, DO SOME WORK IN THE LABORATORY. SO IT'S WORKED OUT REALLY WELL, REALLY THAT EDUCATION PROCESS HAS CONTINUED AND THE POSTDOCS NOW TEACH THE NEW POSTDOCS AND PEOPLE ARE NOT AS NERVOUS. THERE ARE SOME INTERESTING QUESTIONS THAT COME FROM THESE CONFERENCES, ESPECIALLY WITH THE LITTLE KIDS. ONE HAD BEEN TO A CAREER DAY SOMEONE MENTIONED GETTING PAID ON COMMISSION. THEY ASKED A POSTDOC, DO YOU GET PAID ON COMMISSION? THAT'S A GREAT IDEA! IF THEY GET A PUBLICATION, THEY GET PAID. SO THE CONFERENCE ACTUALLY WE'VE BEEN DOING SINCE 1997, MDA WAS INVOLVED AND SO IT'S REALLY WORKED WELL. JUST TO HIGHLIGHT THE CLINICAL STUDY, NOT SHOWING ANYTHING FROM THE CLINIC BUT THIS IS KATHY WITH ONE OF OUR PATIENTS AT ONE OF THE RECEPTIONS BUT THE CLINICAL EXAMS ARE QUITE IMPORTANT, NEW CHILDREN'S HOSPITAL AT IOWA, REALLY IT'S A REALLY GOOD WAY OF GETTING EVERYONE TOGETHER. I THINK ALSO BECAUSE ALL THE PATIENTS ARE PARTICIPATING, THEY TALK, WE GET MORE PARTICIPATION DURING THIS WEEKEND. SO THE LAB TOURS HAVE DIFFERENT STATIONS, MUSCLE BIOPSY STATION THAT STEVE MOORE RUNS, WHERE WE SHOW HOW TO DO WESTERN BLOTS, PROTEIN ANALYSIS, MICE RUNNING ON TREADMILLS, ALTHOUGH RIGHT NOW WE SHOW MOVIES OF MICE RUNNING ON TREADMILLS. THEY WERE GETTING NERVOUS ABOUT ACTUALLY US BRINGING OUR MICE TO THE LABORATORY. AND DIFFERENT TECHNIQUES. IT'S AMAZING THE QUESTIONS. NEW FAMILY MEMBERS REALLY WANT TO SEE THE BASICS. PEOPLE WITH US A NUMBER OF YEARS CAN ASK REALLY GOOD QUESTIONS. I REMEMBER ONCE WE HAD WHEN WE FIRST WERE DOING THESE CONFERENCES, ALSO DUCHENNE MUSCULAR DYSTROPHY PATIENTS, ONE FATHER ASKED US, YOU KNOW, MY BROTHER HAS DIABETES AND THEY GIVE HIM INSULIN SHOTS. MY SON IS MISSING DYSTROPHIN, HOW COME YOU CAN'T GIVE DYSTROPHIN SHOTS? IT'S IMPORTANT FOR MEDICAL STUDENTS TO HEAR THE QUESTIONS. THEY ARE GOING TO GET THESE QUESTIONS WHEN THEY SEE PATIENTS IN THE CLINIC. THE LAB ON FRIDAY, T-SHIRTS, WE GIVE T-SHIRTS OUT. A ROOM WHERE PEOPLE COME AND THERE'S QUESTIONS AND PEOPLE TALKING ABOUT THE SCIENCE THERE. WE CAN HAVE FOOD IN THAT AREA. WE CAN'T HAVE FOOD IN THE LABORATORY. THEY START GOING THROUGH THE LABORATORY AND THEY ARE EXPLAINED DIFFERENT STATIONS, DIFFERENT TECHNIQUES. WE HAVE THE UNDERGRADS PARTICIPATING, REALLY THIS CONFERENCE, YOU THINK ABOUT IT, IT'S EDUCATION FOR THE FAMILIES, BUT IT'S AS MUCH EDUCATION FOR THE LABORATORY AS IT IS FOR THE FAMILIES. THE TWO THINGS, YOU KNOW, I MYSELF, I'M A BASIC SCIENTIST. WE HAVE A FEW CLINICIANS IN THE LABORATORY BUT MOST OF THE YOUNG PEOPLE ARE NOT CLINICIANS AND SO THEY ARE NERVOUS ABOUT MEETING PATIENTS. AFTER THEY MEET THEM THEY GET EXCITED ABOUT THE SCIENCE. I THINK IT ALSO SHOWS THEM, YOU KNOW, THERE ARE PEOPLE REALLY INTERESTED IN WHAT THEY ARE DOING. A NUMBER OF TIMES PARENTS HAVE GIVEN THEM THEIR CELL PHONE NUMBERS AND SAID IF YOU EVER GET DISCOURAGED, CALL ME AT NIGHT AND I'LL GIVE YOU A PEP TALK. SO IT WORKS BOTH WAYS. THERE'S GLEN. HE WAS AT THIS YEAR'S CONFERENCE, AT THE LAB TOURS. THAT'S THE T-SHIRT. AND THE JAPANESE FELLOWS ARE AGAIN NERVOUS BECAUSE THEY HAVE TO SPEAK TO FAMILIES IN ENGLISH. NOW WE HAVE A FEW JAPANESE FAMILIES COMING THROUGH, THEY CAN USE THEIR JAPANESE. THESE ARE MORE PICTURES. THIS IS JOHN WHO HAD DONE MYOTONIC DYSTROPHY WORK. THAT'S THE T-SHIRT. WE HAVE ONE EACH YEAR. ON SATURDAY THE FAMILY MEMBERS AND PATIENTS GET THE T-SHIRT AND THEY GET -- THEY LIKE THAT AS A SOUVENIR. THIS IS THE LAYOUT. I DON'T EXPECT YOU TO SEE ALL THIS BUT IT STARTS VERY EARLY. AND THERE'S A NUMBER OF DIFFERENT TALKS. ONE OF THE THINGS YOU'LL SEE IS THERE'S A MIXTURE OF OUTSIDE AND INSIDE SPEAKERS. SO WE TRY TO GET ERIC OLSON TO SPEAK ON CRISPR THIS YEAR. HE SENT RHONDA. WE HAVE A MIXTURE OF OUTSIDE AND INSIDE SPEAKERS. DURING THE CONFERENCE OR SOMETIMES BEFORE THE CONFERENCE AT THE FAMILY TOURS I TELL THEM ABOUT THE ORGANIZATION OF THE WELLSTONE CENTER. SO WE REALLY HAVE TWO PROJECTS, A PRE-CLINICAL IN MY LABORATORY AND TRANSLATIONAL THAT KATHY HAS THE CLINICAL STUDY, AND STEVE MOORE RUNS THE CORE, PATIENT DIAGNOSTIC CORE, WHERE THERE ARE MUSCLE BIOPSIES AND PATIENT FIBROBLAST CELLS, AND THE GLUE THAT HOLDS US TOGETHER IS THE MONTHLY NEUROPATH CONFERENCE WHETHER WE MEET AND DISCUSSION NEW BIOPSIES AND NEW PATIENTS THAT HAVE COME TO THE CLINIC AND NEW SAMPLES ISN'T TO THE UNIVERSITY OF IOWA. THAT'S WHAT WE'VE BEEN DOING ALL THIS TIME. THAT'S REALLY GROWING RIGHT NOW. AND THERE ARE OTHER GROUPS JOINING US, MIKE SHY'S GROUP IS JOINING US NOW, AND WE REALLY HAVE A REALLY GOOD CONFERENCE ONCE A MONTH, AND A LOT OF THE STUDENTS PRESENT, AND KATHY MATTHEWS AND STEVE MOORE PRESENT, AND SO THAT'S REALLY THE GLUE FOR THE ENTIRE CENTER. AND THEN WE'RE SUPPORTED BY SEVERAL CORES, INCLUDING THE RESEARCH TRAINING CORE WHICH I'LL EXPLAIN IN A MOMENT. ONE THING I ALWAYS WANT TO TELL THEM IS HOW IMPORTANT THEIR SAMPLES THAT THEY DONATE ARE. AND THIS IS AN EXAMPLE WHERE YEARS AGO WE STARTED COLLECTING PATIENT FIBROBLASTS, AND, YOU KNOW, WE REALLY DIDN'T KNOW WHAT WE WERE GOING TO DO WITH THEM. AND THEN IN MAYBE 2009 ONE POSTDOC CAME TO THE LAB AND FIGURED OUT WE COULD USE THE PATIENT FIBROBLASTS FOR THE DYSTROGLYCANOPATHY, THAT LED TO A PAPER AND IDENTIFIED FIVE NEW GENES. I'D LIKE TO EXPLAIN THEY ARE DONATING SAMPLES, THEY CAN GO TO STEVE MOORE'S LAB AND GET DE-IDENTIFIED AND COME TO YOUR LAB FOR RESEARCH AND THEY ARE GRIOT USEFUL QUITE USEFUL. PROBLEMS WITH THE DYSTROGLYCANOPATHYS, THE PATIENTS HAVE NOT BEEN PREVIOUSLY IDENTIFIED, THE GENES ARE COMPLICATED AND LOTS OF NEW CASES REALLY HAVE TO INVOLVE EXOME SEQUENCING TO IDENTIFY GENES. I EXPLAINED GLYCOBIOLOGY, JUST A LITTLE BIT. EVEN SCIENCE, A LOT OF PEOPLE DON'T LIKE TO HEAR ABOUT GLYCOBIOLOGY. I EXPLAIN RECENT FINDINGS, CRYSTAL STRUCTURE OF GLYCAN BINDING, AND THERE'S TWO SUGARS WITH THE INTERACTION, QUITE SURPRISING, IT'S REALLY A GLYCAN PROTEIN INTERACTION AT THE END OF THE DAY IS WHAT'S MORE THAN TO KEEP BASEMENT MEMBRANE OF MUSCLE ATTACHED TO THE LAMININ MEMBRANE. SOME PARENTS WANT TO HEAR ALL THE GORY DETAILS OF THE SCIENCE. THIS IS A SLIDE FROM LAST YEAR ABOUT MY DREAM OUTLOOKS IN ITEMS OF THERAPY, SOME WORK DONE AT IOWA, ALSO WORKING WITH COMPANIES THINKING ABOUT DYSTROGLYCANOPATHY. THIS IS MENTIONED, SOME OF THE SPEAKERS. THEY VARY FROM RHONDA WHO GAVE A NICE TALK ON CRISPR TECHNIQUES, WE HAVE MELISSA GROVE FROM TEXAS, A GREAT TALK ON LIVING WITH MUSCULAR DYSTROPHY, IF YOU'VE NEVER HEARD HER SPEAK YOU REALLY SHOULD HAVE HER COME VISIT. WE HAVE A TALK FROM THE OUTSIDE PERSON LIKE GLEN THIS LAST YEAR AND DIFFERENT PANEL DISCUSSIONS. THAT JUST EXPLAINS THAT. THESE ARE BREAKOUT SESSIONS IN THE AFTERNOON. WE HAVE A QUESTION AND ANSWER SESSION FOR STEVE AND I, KATHY HAS A SESSION ON MANAGEMENT, AND THIS IS ACTUALLY QUITE NICE. THE GROUPS ARE SMALLER AT THIS STAGE, SOMETIMES WE HAVE LIKE 150 PATIENTS AND FAMILY MEMBERS AT THE MEETING. THESE GROUPS ARE DOWN TO 10 TO 20 AND THEY GET TO ASK QUESTIONS. THIS IS FROM MELISSA GROVE'S AND DIFFERENT KIND OF NEAT KIND OF TIPS TO REALLY HELP PEOPLE TO KEEP THEIR CELL PHONE ON THEM WHEREVER THEY GO, THIS IS QUITE POPULAR AND WE PUT THIS OUT AND WE DEVELOP IT DURING THE CONFERENCE AND WE ALSO HAND IT OUT AFTER THEY LEAVE AND SEND IT TO THEM. ONE THING THAT'S HAPPENED MORE RECENTLY IS WE HAVE LGMD2I PATIENTS, AND THESE PATIENTS ARE USUALLY LATE TEENS OR EARLY 20s, LOOKING AT COLLEGES. SO WE HAVE NOW IN ONE AFTERNOON TOURS OF THE UNIVERSITY OF IOWA. THIS IS FOR THE PATIENTS THAT WERE GIVEN A TOUR, AND WERE DOING SOMETHING TO SEE IF THEY WERE INTERESTED IN GOING TO UNIVERSITY OF IOWA FOR COLLEGE. I ALSO EXPLAINED EDUCATION COMPONENT THAT WE HAVE, AND THIS IS KIND OF UNIQUE. WE HAVE A MEDICAL STUDENT PROGRAM THAT'S RUN BETWEEN KATHY AND MYSELF. THIS MEDICAL STUDENT TAKES A YEAR OFF FROM SCHOOL AND ACTUALLY THEN WORKS IN THE CENTER. MONDAY MY LAB OR STEVE'S LAB, TRANSLATIONAL RESEARCH WITH PATIENT CELLS. TUESDAYS THEY SPEND THE DAY IN THE CLINIC WITH KATHY MATTHEWS. ALL THE OUTREACH CLINICS, MDA SUMMER CAMP. WEDNESDAY WITH STEVE MOORE IN NEUROPATH, THE OFFICIAL HOSPITAL NEUROPATH, THURSDAY AND FRIDAY SPLIT BETWEEN MY AND KATHY'S LAB. THEY HAVE DONE THE JOB OF ALL OF US AN GET EXCITED ABOUT NEUROMUSCULAR DISEASE RESEARCH. THE GOAL WAS NOT TO GET THEM TO BECOME SCIENTISTS BUT GET THEM TO BECOME PEDIATRIC NEUROLOGISTS, THIS CAME ABOUT WHEN WE WERE ASKED TO PUT IN A TRAINING GOAL. WE FOUND THERE WERE A NEED FOR PEDIATRIC NEUROLOGISTS. MY FORMER CHAIR'S GRANDSON HAS MUSCULAR DYSTROPHY, THEIR FAMILY LIVES IN CALIFORNIA. THEY HAD A REALLY HARD TIME FINDING A PHYSICIAN. SO THE GOAL OF THIS IS TO GET THEM EXCITED AND TO START THEM EARLY. ONCE THEY ARE IN THE THIRD OR FOURTH YEAR OF MEDICAL SCHOOL THEY ARE INTERESTED IN DERMATOLOGY, RADIOLOGY, OTHER AREAS. IF YOU CATCH THEM FIRST OR SECOND YEAR, THEY GET INTERESTED AND EXCITED ABOUT WORKING WITH FAMILY MEMBERS THEY GET HOOKED. WE'VE BEEN VERY SUCCESSFUL GETTING THEM INTO PEDIATRIC NEUROLOGY. AND THEY ALSO ARE A REALLY NICE GROUP, THEY BRING THE FAMILIES OVER FOR TOURS. THEY ALSO TELL THEM ABOUT THE POSTDOCS AT MY LABORATORY, I'LL TALK MORE ABOUT THAT THIS AFTERNOON. ONE CONCERN IS PEOPLE SEE THE POSTDOCS LEAVE. THEY SAY NO ONE IS WORKING ON THIS PROJECT, WHAT'S HAPPENING? SO I TRY TO EXPLAIN THEY GO OFF TO UNIVERSITIES AND COMPANIES AND CONTINUE TO WORK ON MUSCULAR DYSTROPHY, AND I ILLUSTRATE SOME PROJECTS. LIKE YVONNE WENT TO LILLY, INVOLVED IN CLINICAL TRIALS. IT'S REALLY NOT LOSING PEOPLE TO THE FIELD, IT'S LETTING THEM GO AND EXPANDING THAT AND NEW PEOPLE COME INTO THE LAB. WE TALK ABOUT THE UNDERGRADS. THIS IS THE NEXT GENERATION OF YOUNG SCIENTISTS, AND THE UNDERGRADS ARE REALLY IMPORTANT FOR RUNNING THE RESEARCH LAB AND ALSO ARE INVOLVED IN MUSCULAR DYSTROPHY WORK. AND THEN WE USUALLY HAVE A PICTURE AT THE END WHEN WE CAN TRY TO FIT EVERYONE IN, AND WE SEND THIS BACK AFTER THEY LEAVE. AND WE ACKNOWLEDGE THE SUPPORT. WE USE SOME WELLSTONE MONEY FOR THE CONFERENCE BUT WE NEED LOTS OF SUPPORT FROM OTHER GROUPS AND I LIKE TO THANK THE GROUPS THAT HELPED OVER THE YEARS BOTH FOR THE MEALS, RECEPTIONS, AND ALSO GETTING THE PATIENTS TO IOWA CITY, ALWAYS NOT THAT EASY. >> I'LL END THERE. >> AND HOPEFULLY NOT IN THE WINTER. >> NEVER IN THE WINTER. [APPLAUSE] >> I THINK YOUR POINT THAT YOU MAKE, KEVIN, IN TERMS OF PATIENT PARTICIPATION AND FAMILY PARTICIPATION IN ALL OF THESE, PARTICULARLY RARE DISEASES, IS SO IMPORTANT BECAUSE PEOPLE GET EXCITED TO KNOW THAT SOMEBODY'S ACTUALLY WORKING ON THEIR PROBLEM. THERE'S NOTHING LIKE IT. WHEN WE HAVE MANY GROUPS COME TO VISIT US, THE -- ONE OF THE MAIN QUESTIONS IS HOW DO WE GET PEOPLE TO WORK ON OUR PROBLEMS? I THINK THAT'S WHAT WE'RE GOING TO FOCUS ON THIS AFTERNOON. WE'LL COME BACK TO SOME EXAMPLES. WE DO HAVE TIME FOR QUESTIONS. I WANT TO JUST START BY GOING BACK TO DAN PEREZ, THE VERY INTERESTING CONFERENCE THAT YOU HAD, THE INTERNATIONAL CONFERENCE, DAN. PART OF THE CONFERENCE, DID IT ADDRESS THE AREA OF TRAINING? WE'LL TALK MORE ABOUT TRAINING BUT WAS THERE A DISCUSSION ABOUT TRAINING AT YOUR MEETING IN TERMS OF THE NEXT GENERATION OF INVESTIGATORS INTO THIS EXCITING NEW SCIENCE? >> I THINK TO ANSWER THE QUESTION, WE DID NOT HAVE A SESSION ON WRITING GRANTS. I GUESS WOVEN RIGHT INTO THE MEETING, WE'VE GOT PRE-DOCS, GRADUATE STUDENTS, POSTDOCS, ALL IN ATTENDANCE. AND -- >> THAT'S REALLY WHAT I MEANT, NOT GRANT WRITING BUT PARTICIPATION OF POSTDOCS AT THE MEETING TO GET THEM EXCITED IN SCIENCE. >> THEY ARE USUALLY PRESENT PRESENTING POSTERS, PRESENTING WORK, INTERACTION WITH INDUSTRY AND ESSENTIALLY SCIENTIFICALLY ORIENTED PATIENTS. AS KEVIN MENTIONED, WHEN THEY INTERACT WITH THE PATIENTS THEY REALLY GET JAZZED UP TO WORK ON THE PROBLEM MORE. WE -- I GUESS WE TRY TO PUSH IT FORWARD AND WHAT ARE THE IDEAS THAT WE NEED TO HAVE PEOPLE PUT FORTH AND WRITE GRANTS ON AND GET FUNDING FOR. I GUESS THERE'S A LOT OF -- THE SOCIETY INITIATES A LOT OF WORK OR SWEET SPOT, QUOTE, DOCTORAL FELLOWSHIPS, AND INITIATING FUNDS, THAT KIND OF THINGS. IT SORT OF SHOWCASED, THERE'S ALSO ACKNOWLEDGMENT FROM LEADERS, WHEN THEY STARTED THEIR CAREERS WITH SOCIETY FELLOWSHIPS, THAT KIND OF THING. SO -- AND THEN IN TERMS OF CLINICAL ASPECTS, KATHERINE WAGNER WAS AT THE MEETING. KATHERINE, PERHAPS YOU COULD COVER THAT LATER, WHAT THE CLINICAL FELLOWS ARE ALSO DOING, PRESENT IN OUR LAB, THE WELLSTONE -- ALSO THE WELLSTONE. STEPHEN MOORE DID A GREAT JOB WITH EFFICACY TESTING DATA THAT THEY PRESENTED AT THIS MEETING, I WANT TO DO A SHOUT OUT FOR KEVIN AND STEVE MOORE. ANYWAY, I THINK IT'S INHERENT IN THE -- YOU KNOW, IN THE ENGAGEMENT PROCESS. >> THANK YOU. THANK YOU. QUESTIONS FROM THE FLOOR? BRIAN? IDENTIFY YOURSELF IF YOU'RE ASKING A QUESTION OF ANYBODY ON THE PHONE. >> BRIAN DENGER. MY COMMENT IS FOR DR. CAMPBELL. YOUR DISCUSSION ABOUT THE FAMILIES VISITING THE LABORATORIES, FOR THE PAST HALF DOZEN OR MORE YEARS, I LIVE IN MAINE, WE VISIT THE JACKSON LABORATORIES, OUR FAMILY DOESN'T GO TO A MOUSE REPOSITORY FOR A SUMMER VACATION, BUT ONE OF THE FIRST YEARS WE WENT MY YOUNGEST WANTED TO SEE THE MICE, AND THEY ALLOWED HIM TO SEE ONE OF THE MICE CLOSE UP. AND YOUR COMMENT ABOUT THE CONCERN WAS VALID BECAUSE HE GOT BIT AND I REMEMBER THE GOVERNMENT AFFAIRS WOMAN BEING QUITE UPSET AND WE HAD HE TO SIGN A FEW RELEASES. BUT THE RELATIONSHIP THAT WE BUILD, I MEAN, THAT WAS JUST A MINOR ASIDE, BUT THE RELATIONSHIP THAT WE HAVE BUILT OVER THE YEARS RESONATES DEEPLY WITH THE PEOPLE WHO WORK IN THE LABORATORY, THEY ARE ISOLATED, IT'S NOT CLINICALLY BASED. SO WHEN WE COME, THEY GET TO SEE TANGIBLE EVIDENCE AND FEEDBACK FROM WITHIN THE COMMUNITY ABOUT HOW IMPORTANT THEIR WORK IS. >> JOHN? >> A COMMENT ON THAT. I USUALLY EXPLAIN TO THE FAMILIES WHEN YOU'RE DOING REAL RESEARCH, MOST THINGS DON'T WORK. SOMETIMES SIX MONTHS TO A YEAR, YOU KNOW, IT REALLY IS KIND OF -- IT CAN BE DISCOURAGING. MY WIFE SAID YOU'RE ALWAYS HAPPY. 30 PEOPLE IN THE LAB, SO EVERY DAY ONE THING WORKS. [LAUGHTER] THE AVERAGE YOUNG INVESTIGATORS, POSTDOC OR YOUNG STUDENT, MOST OF THE TIME THINGS ARE NOT WORKING. THE FAMILY MEMBERS GIVE THEM, YOU KNOW, SOME BOOST TO GET AROUND THAT. >> SO DAN, I THINK THERE'S KIND OF THE CASE STUDY WITH WHAT YOU'VE DONE WITH FSHD IN GENERAL, AND WITH THE MEETINGS, IN HOW THE FIELD BUILDS. SO BACK IN THE PRE-LATE 2011 DAYS WHEN YOU DIDN'T HAVE GENETIC MECHANIC MECHANISM FOR THE DISORDER IT WAS LARD TO GET FUNDED. SINCE THAT'S IN PLACE THE FIELD HAS TAKEN OFF. ONE THING ENCOURAGING TO ME IS SEEING THE GROWTH IN THE CORPORATE INVOLVEMENT WITH FSH, THE TRIALS GOING ON OR GETTING READY TO MOVE, AND I THINK THERE'S IMPORTANT LESSONS THERE. IF WE LOOK AT THE MDCC AS GENERATING LESSONS FOR OTHER DISEASE GROUPS THAT COVER THIS SPACE, THERE'S SOME IMPORTANT LESSONS THERE. FIRST TO CONGRATULATE YOU ON HOW THAT'S BUILT. THE SECOND THING, A LOT OF CRITICAL NEEDS, JOTTING SOME DOWN WHILE YOU TALKED, AND THINGS LIKE SURROGATE OUTCOMES, VALIDATED OUTCOMES, ADDITIONAL NATURAL HISTORY, SUBGROUPING OF PATIENTS, DISEASE MODIFIERS, INVOLVEMENT OF INDUSTRY AND PRIORITIZATION OF PRE-CLINICAL AND CLINICAL TOOLS, THESE ARE AGAIN COMMON TO ALL THE MUSCULAR DYSTROPHYs. WE ALL HAVE EXACTLY THE SAME PROBLEMS WE HAVE TO WORK ON. SO, YOU KNOW, I WOULD ENCOURAGE THE MDCC TO THINK ABOUT THESE LESSONS THAT CROSS ALL OF OUR DISEASES AND THAT OTHER GROUPS MAY BENEFIT FROM THINGS THAT PARTICULAR GROUPS HAVE ALREADY ACCOMPLISHED. MY QUESTION, DAN, IS THAT YOU BROUGHT UP AN INTERESTING CONCEPT ON HOW TO BUILD TRIAL READINESS THROUGH NATURAL HISTORY STUDIES. YOU MENTIONED AMR, WHERE THE WEALTH, THE DATA IS YOUR CLINICAL TESTING DATA VERSUS DESIGNATED NATURAL HISTORY STUDIES WHERE DATA COLLECTED ARE REALLY ENDPOINT MEASURES, CLINICAL TRIAL ENDPOINT MEASURES. WHAT DOES THE GROUP THINK ABOUT THE RELATIVE VALUE OF COLLECTING EMR DATA, ROUTINE LAB TESTS AND EVERYTHING, VERSUS THE DESIGNATED NATURAL HISTORY STUDIES IN WHETHER YOU COULD USE EMRs AND YOU COULD GO AFTER THAT ROUTINE DATA AND BUILD A NATURAL HISTORY DATASET THAT REALLY ALSO HELPS WITH THE CLINICAL TRIAL DESIGN WITH ENDPOINT MEASURE DESIGN? ANYBODY HAVE ANY THOUGHTS ON THAT? >> MAYBE VALERIE. >> THERE WE GO. SO THAT'S SOMETHING THAT WE ARE VERY INTERESTED IN. WE'VE BEEN PILOTING A REGISTRY FOR THREE YEARS NOW, COLLECTING DATA FROM THE CLINICAL VISIT. WE DON'T HAVE THE TOOL YET TO DIRECTLY DOWNLOAD FROM THE EMR BUT WE'RE WORKING ON THAT, THAT'S THE ONLY WAY WE'LL BE ABLE TO COLLECT LARGE AMOUNTS OF DATA FROM CLINICAL VISITS. NOW, AS YOU SUGGESTED, THERE'S A DIFFERENCE BETWEEN WHAT YOU COLLECT AT THE CLINICAL VISIT VERSUS WHAT YOU COLLECT, YOU KNOW, IN A TRUE NATURAL HISTORY STUDY OR IN A CLINICAL TRIAL. AND IT COMES BACK TO THIS ISSUE OF WHAT'S CLINICALLY MEANINGFUL TO PATIENTS. YOU KNOW, ARE WE COLLECTING THE RIGHT DATA IN THE NATURAL HISTORY STUDIES? AND, YOU KNOW, I THINK THAT'S STILL A BIG QUESTION IN A NUMBER OF OUR DISEASES. SO ARE THERE SOME MEASURES THAT WE CAN ADD TO THE CLINICAL EXAM THAT AREN'T GOING TO NECESSARILY LENGTHEN THE CLINICAL EXAM SIGNIFICANTLY, BUT CAN HELP US WITH THE NATURAL HISTORY INFORMATION? >> I WANTED TO ADD TO THAT COMMENT. I THINK ONE OF THE NUANCES THAT CAME OUT IN OUR DISCRETION WAS THE DESIGN OF A CLINICAL SCALE, KATHERINE YOU CAN HELP ME IF I DON'T GET THIS RIGHT. FOR EXAMPLE, THE HUNTINGTON DISEASE HAS UNIFORM SCALE, THE WHOLE WAY WE MEASURE PATIENTS IS AROUND MOVEMENT. AND SO IT'S NOT NECESSARILY THAT THE DRUG IS DISEASE MODIFYING, BUT THAT WE'RE MODIFYING THE MOVEMENT, AND SO A LOT OF THE DISCUSSIONS WERE REALLY AROUND WE NEED TO DESIGN A THERAPY OR MODALITY, WE NEED TO THINK CAREFULLY AROUND HOW THAT AFFECTS THE SCALE. SO FOR EXAMPLE HUNTINGTON'S, THE ONLY APPROVED DRUG -- I DON'T KNOW IF I HAVE THE RIGHT TERM, RENDOZINE OR SOMETHING, CUT DOWN MOVEMENT WHICH THEN IS A STANDARD OF CARE, WITH TRIALS, CAN REDUCE DYNAMIC RANGE OF YOUR MEASUREMENT. SO I THINK SOME OF THE DISCUSSIONS WERE AROUND THAT SORT OF THINKING ABOUT THOUGHTFULLY AS WE MOVE SMALL MOLECULE GENE THERAPY DISEASE MODIFYING OR IN TERMS OF FUNCTIONAL MODIFICATIONS, THAT THOSE KIND OF INTERACTIONS. >> YEAH, SO I THINK EMR CERTAINLY IS A GOOD SOURCE OF INFORMATION BUT I'M NOT SURE IN TERMS OF FDA, FDA IS LOOKING FOR MEANINGFUL BENEFIT, NOT CLINICALLY MEANINGFUL BENEFIT BUT WHAT MATTERS TO THE PATIENT. AND WHAT CHANGES IN THEIR LIFE BASED ON INTERVENTION. SO I THINK PATIENT REPORTED OUTCOME MEASURES HAVE TO BE INTEGRATED SO WE FULLY UNDERSTAND WHAT'S GOING ON IN THE PATIENT'S LIFE. I ALSO KNOW THAT WITH SHORTENED VISITS, PEOPLE GOING TO LOCAL CLINICS, MOST OF THE BIG CBCCs OR BIGGER CLINICS PATIENTS ARE FLYING TO AREN'T GOING TO BE WHERE THEY RECEIVE LOCAL CARE ONCE THERE ARE THERAPIES SO WE HAVE TO HAVE A MEANS, FIRST OF ALL I THINK THAT THE ACADEMIC NATURAL HISTORY DATABASES AT NIH HAGS FUNDED NEED TO BE ORGANIZED AND NEED TO BE INTEGRATED BECAUSE LOOKING AT INDIVIDUAL DATASETS IS NOT IT'S A HELPFUL AS LOOKING AT INTEGRATED DATASET, THAT WOULD BE THE FIRST THING. CERTAINLY THE EMRs ARE AN INTERESTING IDEA IF YOU CAN EXTRAPOLATE FROM PDF, SOME TECHNOLOGIES ARE DOING THAT. EMPOWERING PATIENTS TO DO PATIENT-REPORTED OUTCOMES IN SYSTEMATIC RIGOROUS WAY THIS IS HOW DATA IS GOING TO BE COLLECTED AND WE'LL HAVE TO KNOW IT'S MEANINGFUL TO THEM OR THEY ARE NOT COMPLIANT WITH THERAPIES. WE HAVE TO THINK THROUGH THIS WORK TOGETHER. GET RIGOROUS ORGANIZED WAY OF COLLECTING AND INTEGRATING THIS DATA SO WE'RE DOING AND SERVING THE PATIENTS THE BEST WAY POSSIBLE. >> I COULDN'T AGREE WITH YOU MORE, JUST A NOTE ABOUT ELECTRONIC HEALTH RECORDS, THEY ARE REALLY NOT MEANT FOR PATIENT OBSERVATION. I MEAN, THEY ARE REPLETE WITH MISTAKE UPON MISTAKE, PROPAGATED FROM ONE TO THE NEXT, AND OF COURSE YOU MIGHT SAY IT'S A PLACE TO START, BUT THAT'S NOT WHERE I WOULD GO BASICALLY. THAT'S NOT WHERE WE'RE GOING. >> MY HUSBAND'S PRACTICE CALLS THEM A CRYPTIC ANSWER TO WHAT MAY BE HAPPENING. I THINK PATIENT-REPORTED OUTCOMES, WE HAVE TO DO IT DIFFERENTLY. >> I AGREE. PETER? >> SO, JOHN, JUST A CURIOUS QUESTION BACK TO YOU. I MEAN, CERTAINLY WHERE I PRACTICE, SPECIALIZED OCCUPATIONAL MEDICINE OR ADULT, THEIR STANDARD EMR IS ABSOLUTELY NO USE TO US. AND THE EMR THAT WE ACTUALLY USE IS A FAIRLY HIGHLY -- NOT HIGHLY, BUT A SPECIALIZED SUBSET OF THE EMR WHERE SPECIFIC QUESTIONS ARE ASKED ABOUT STUFF WE'RE INTERESTED IN. IF WE GO TO LIKE A GENERAL PRACTICE AND TRY TO EXTRAPOLATE THINGS THAT WE'RE INTERESTED IN FROM THE GENERAL EMR, I THINK IT DOESN'T HELP US AT ALL. AND SO IT STRIKES ME THAT SPECIFICALLY FOR NEUROMUSCULAR DISEASE IF WE GO TO A STANDARD EMR AND LOOK FOR THINGS WE'RE NOT GOING TO FIND AT ALL WHAT WE NEED, AND MAYBE -- AND SO I'M NOT SURE THAT'S ACTUALLY WHAT YOU MEANT, BUT IT SEEMS THAT IF WE HAD A SPECIALIZED SUBSET OF COMPONENT EXAM, SPECIFICALLY AROUND THINGS THAT PATIENTS FOUND TO BE CLINICALLY SIGNIFICANT, THAT WOULD BE REALLY HELPFUL. BUT I DON'T THINK WE'LL GET IT FROM A STANDARD EMR. >> WE'RE LOOK TECH IDEA, THE REASON WE'RE LOOKING AT THIS IS THAT -- I COMPLETELY AGREE, CLINICALLY RELEVANT MEASURES, PATIENT-REPORTED OUTCOMES, THOSE ARE GOING TO BE THE THINGS THAT FDA NEEDS. BUT THE REAL WORLD IS WE'RE NOT GOING TO HAVE -- EVERY NEUROLOGIST IN THE COUNTRY THAT SEES ONE OF OUR PATIENTS IMPLEMENTING PATIENT REPORTED OUTCOME MEASURE, WE'RE NOT GOING TO HAVE THAT. SO THE REASON WE'RE INTERESTED IN THIS IS WHAT CAN WE EXTRACT FROM JUST BASIC CASE -- YOU KNOW, BASIC CLINICAL REPORTING ON A PHYSICIAN BY PHYSICIAN BASIS. WHAT CAN WE EXTRACT FROM THAT? AND WHEN DAN RAISED THE QUESTION, I THOUGHT -- I MEAN RAISED THE POINT ABOUT EMRs, IT TRIGGERED THE THOUGHT ABOUT HOW VALUABLE CAN THIS DATA BE? MAYBE WE DON'T KNOW HOW VALUABLE IT IS UNTIL WE'VE COLLECTED AND SEE WHAT WE CAN DO LIKE WHAT YOU'RE DOING, VALERIE, YOU KNOW. BUT I'M NOT TALKING ABOUT SUBSTITUTE. I COMPETELY AGREE, PROVE AND ENDPOINTS, BUT WHAT IF YOU COULD GET THIS KIND OF DATA FROM THOUSANDS OF PATIENTS AS OPPOSED TO A COUPLE HUNDRED IN A NATURAL HISTORY STUDY? WOULD THERE BE VALUE? IT'S A QUESTION. I'M NOT PUSHING THE IDEA. IT'S A QUESTION. >> THE OTHER THING IS LOOKING AT COMPLIANCE WITH STANDARDS OF CARE, DOES THAT CHANGE OUTCOMES, BECAUSE AS WE ALL KNOW THE STANDARDS OF CARE THAT HAVE BEEN DEVELOPED HAVE PRIMARILY BEEN BASED ON CONSENSUS AND EXPERT OPINION, NOT ON A LOT OF EVIDENCE. SO, YOU KNOW, YOU CAN ASK SOME QUESTIONS RELATED TO THOSE CARE GUIDELINES, STANDARDS OF CARE PERHAPS, YOU WON'T BE ABLE TO LOOK AT THE ENTIRE, YOU KNOW, STANDARD -- YOU KNOW, CARE CONSIDERATIONS GUIDELINE FOR DUCHENNE OR OTHER CARE GUIDELINES, YOU KNOW, THOSE ARE JUST TOO MASSIVE, BUT THERE MAY BE KEY QUESTIONS THAT CAN BE ASKED WHETHER YOU CAN, YOU KNOW, FOLLOW THE CLINICAL DATA LONGITUDINALLY. >> RELEVANT TO THAT, I'M GOING TO TAKE THE -- TRY TO TAKE THE CHAIR'S PREROGATIVE TO ASK THE LAST QUESTION. I'D LIKE TO ASK KATHY, IT RELATES TO WHAT YOU'RE TALKING ABOUT. CHRONIC INGESTION OF CORTICOSTEROIDS, AT LEAST IN ADULTS, DOES HAVE A STANDARD OF CARE. AND THAT IS AFTER THREE MONTHS, RECOMMENDED, EITHER BY AMERICAN SOCIETY FOR BONE AND MINERAL RESEARCH, WHETHER IT'S THE AMERICAN COLLEGE OF RHEUMATOLOGY, DOES ASK THAT THE PHYSICIAN PAY ATTENTION TO BONES IN TERMS OF BONE PRESERVATION. WHATEVER THE IMPLEMENTATION IS. WHAT YOU SEEMED TO SAY WAS THAT'S NOT SO CLEAR IN CHILDREN. IN OTHER WORDS, CHRONIC ADMINISTRATION OF CORTICOSTEROIDS IS UNKNOWN IN TERMS OF HOW TO INTERFERE, HOW TO INFLUENCE THAT, AND I WONDER, IS THAT REALLY RIGHT? IS THERE NO STANDARD OF CARE FOR CHILDREN FOR CHRONIC ADMINISTRATION OF CORTICOSTEROIDS? INFLAMMATORY DISEASES, WHAT ABOUT OTHER DISEASES, DO YOU GIVE A KID 10 MILLIGRAMS OF PREDNISONE A DAY, EQUIVALENT, 8 MILLIGRAMS A DAY, IS THERE NO STANDARD REALLY THAT SUGGESTS THAT YOU USE A BISPHOSPHONATE OR SOMETHING LIKE THAT? OR ASTHMA THERE IS. >> (INAUDIBLE). >> UH-HUH. AND FOR MUSCULAR DYSTROPHY? >> SO I THINK SOME OF THESE OTHER CONDITIONS THERE ARE OPTIONS, OTHER AVAILABLE TREATMENTS FOR THE UNDERLYING DISORDER, WHEREAS IN DUCHENNE WE'VE NOT HAD THAT. BECAUSE THERE'S NOT AN ALTERNATIVE MEDICATION, AND THESE STEROIDS ARE THE GOLD STANDARD, STEROIDS HAVE BEEN GIVEN. AND SO FRAGILITY OF BONE HAS BEEN AN EXPECTATION WITHIN THIS DIAGNOSIS AND WITHIN THIS POPULATION. THE CARE GUIDELINES DEVELOPED IN 2010, I ENCOURAGED DEXA SCAN AT BASELINE AND DEXA SCAN EVERY 2-3 YEARS AFTER THAT. AND THEN TREATMENT FOR BONE FRAGILITY PRIME EARLY WITH BISPHOSPHONATES EARLY BASED ON DEXA SCORE. WHEN YOU TO STOP THEM? THE RECOMMENDATIONS FOR DISCONTINUATION ARE WHEN YOU'VE FINISHED GROWING, WHICH WITH DUCHENNE THAT CAN BE MUCH LATER THAN IN NORMAL LIFE, AND WHEN THE THREAT OF FRACTURE OR BONE FRAGILITY IS DECREASED, WHICH IS NEVER IN DUCHENNE. SO THE QUESTION IS WHEN DO YOU START THEM, WHEN DO YOU STOP THEM, WHAT IS THE DOSE? SO BECAUSE OF ALL THAT CONFUSION AND BECAUSE THERE HAVEN'T BEEN BIG STUDIES IN THIS AREA, PEOPLE HAVE BEEN DOING WHAT THEY THOUGHT WAS BEST. AND I WOULD SAY MOST PEOPLE, THE STANDARD OF CARE OF DUCHENNE CARE CENTER IS DEXA AT BASELINE AND EVERY 2-3 YEARS WHICH HAVE BEEN FOLLOWED AT MOST OF THE CENTERS, BUT BECAUSE THERE WAS SUCH CONFUSION WE HELD THIS MEETING TO CLARIFY THOSE ISSUES. WHAT WE'RE FINDING IS VERTEBRAL FRACTURES ARE MORE INDICATIVE OF BROKEN FRAGILITY, ASSESSED BY SPINE FILMS, THAT'S WHY NEW UPDATED CARE GUIDELINES INCLUDE SPINE FILMS IN DEXA, WITH PRIORITY OVER DEXA SHOULD JUST ONE BE AVAILABLE. >> I WAS REFERRING TO PREVENTION, NOT TREATMENT. >> RIGHT. >> IN OTHER WORDS, IT'S PREDICTABLE THAT IF YOU GIVE A KID, AN ADULT, CHRONIC STEROIDS YOU'LL HAVE BONE FRAGILITY. SO HOW DO YOU PREVENT THAT? >> WHAT ARE THE IMPLICATION ALSO OF STARTING BISPHOSPHONATES IF THAT'S THE MECHANISM OF ACTION? >> NOWADAYS WE HAVE MANY OTHER THINGS, MANY OTHER THINGS THAT ARE BONE BUILDING, OR ANTI-RESORPTIVE, NOT NECESSARILY BISPHOSPHONATE. KATHY, YOU HAVE THE LAST WORD. >> THANKS. NOW, I AGREE THAT IN TERMS OF MONITORING, THAT THERE ARE STANDARDS OF CARE WITH DEXA MEASUREMENTS BUT IN TERMS OF ACTUAL TREATMENT IN THE ABSENCE OF FRACTURES, THERE'S NOT UNIFORMITY IN THE FIELD. WHEN A CHILD HAS A FRACTURE, THEN IT'S -- THAT IS ACTUALLY NON-TRAUMATIC FRACTURE, THAT IS THE DEFINITION OF OSTEOPOROSIS, IN THIS GROUP. AND EVERYONE TREATS WITH BISPHOSPHONATES BUT THESE KIDS HAVE LOW BONE DENSITY TO BEGIN WITH AND WE GIVE THEM CORTICOSTEROIDS, AND AS KATHY SAID, BEGINNING AND THE END ARE VERY UNCLEAR AND SO THERE'S WIDE VARIABILITY. >> SO I GUESS I COULD ANNOUNCE IT HERE THAT THE NIH DID AWAY WITH CONCENSUS CONFERENCES BUT WE HAVE CONFERENCES THAT ARE CALLED PATHWAYS TO PREVENTION, AND ONE OF THE CONFERENCES THAT'S GOING TO BE UPCOMING WITHIN THE NEXT YEAR-AND-A-HALF AFTER WE COLLECT DATA IN TERMS OF WHAT'S BEEN DONE IS A PATHWAYS TO PREVENTION OF OSTEOPOROSIS. IT WAS EVEN IN ADULTS, GETTING CHRONIC CORTICOSTEROIDS OR ADULTS HAVE OSTEOPOROSIS, CLOSE TO OSTEOPOROSIS, IT'S UNCLEAR HOW MUCH PREVENTION IS BEING USED BECAUSE OF THE SIDE EFFECTS HAVE BEEN SO WELL PUBLICIZED, PERHAPS TAKEN OUT OF CONTEXT, BUT WE'RE HAVING A GROUP LIKE OUR OLD CONSENSUS CONFERENCES, ADDRESS THAT PARTICULAR QUESTION. AND I THINK THE ADDITION OF CHILDREN IN THERE SHOULD BE SOMETHING WE SHOULD THINK ABOUT. NOW WE'RE GOING TO MOVE ON. WE'RE GOING TO MOVE ON. THANK YOU VERY MUCH FOR THOSE INTERESTING MEETING REPORTS. WE'RE GOING TO MOVE ON FOR THE REST OF THE MORNING ON OUR ATTENTION TO ETHICAL CONSIDERATIONS IN THE DESIGN OF CLINICAL TRIALS. THE DESIGN OF CLINICAL TRIALS IN DUCHENNE MUSCULAR DYSTROPHY HAS RECEIVED, UNLESS YOU DIDN'T KNOW, RECEIVED CONSIDERABLE ATTENTION LATELY AS REGULATORS CONSIDER WHETHER TO APPROVE NOVEL INTERVENTION, MUCH DISCUSSED WILL BE LESSONS LEARNED. THE TOPIC IS RELEVANT TO ALL FORMS OF MUSCULAR DYSTROPHY. I WOULD SAY THE TOPIC IS RELEVANT TO MOST RARE DISEASES FRANKLY FOR WHICH EFFECTIVE TREATMENTS ARE NOT AVAILABLE. WE'RE PLEASED TO HAVE SKIP NELSON OF THE FDA REPRESENTING REGULATORY PERSPECTIVE, PAT FURLONG FROM THE PARENT PROJECT FOR THE PATIENT AND FAMILY PERSPECTIVES, AND BETWEEN AND AFTER THESE PRESENTATIONS WE'RE GOING TO HAVE AN OPEN DISCUSSION OF BEST PRACTICES IN THE ETHICAL DESIGN OF CLINICAL TRIALS FOR THE MUSCULAR DYSTROPHIES THAT WE CAN PROMOTE THROUGH OUR MEMBER ORGANIZATIONS. FIRST PRESENTER IS SKIP NELSON. ACTING DIRECTOR -- IT SAYS IT RIGHT THERE. ANN IS ALSO PRESENTING. >> THE VIEWS I'M TELLING YOU DO NOT REPRESENT ANYTHING OTHER THAN MY OWN PERSONAL VIEWS. I'VE BEEN SCRUBBED CLEAN OF ANY FINANCIAL CONFLICTS. [LAUGHTER] I'M GOING TO COVER THESE TOPICS STARTING WITH A FEW SLIDES TO GIVE YOU THE BASIC ETHICAL FRAMEWORK, THE CONTEXT FOR MY SUBSEQUENT REMARKS. I'M GOING TO MAKE EXTENDED COMMENTS ABOUT MUSCLE BIOPSIES AS A BIOMARKER AND TALK ABOUT ANESTHESIA AND PROCEDURE SEDATION AND COMMENTS AROUND CHOICE OF CONTROL GROUP WHICH GOES TO STUDY DESIGN. I'M GOING TO TALK AT THE END ABOUT SOME SUGGESTIONS FOR IMPROVING THE SYSTEM WHICH I'VE ALREADY HEARD MANY COMMENTS MADE IN SOME REMARKS ALREADY GOING AROUND THE ROOM THIS MORNING. I THINK THAT WOULD JUST BE CONTRIBUTORY. IN ITEMS OF BASIC ETHICAL FRAMEWORK THERE'S FOR PRINCIPLES THAT I LIKE TO START WITH. I DO THIS MAINLY SO PEOPLE DON'T THINK I'M GIVING A REGULATORY TALK BUT I'M TALKING ETHICS. YOU SEE IN THE NEXT SLIDE THE CONNECTION. THE FIRST IS THE PRINCIPLE OF SCIENTIFIC NECESSITY WHICH IS YOU DON'T STUDY KIDS UNLESS YOU NEED TO BASICALLY. IF YOU CAN GET THE ANSWER FROM ADULTS, GET THE ANSWER FROM ADULTS. THE OTHER TWO I'LL TALK ABOUT IN MORE DETAIL WHICH IS ABSENT PROSPECT OF DIRECT THERAPEUTIC BENEFIT, THE RISKS TO WHICH CHILDREN WITH CAN BE EXPOSED MUST BE LOW. CHILDREN SHOULD NOT BE PLACED AT DISADVANTAGE BY EXPOSURE TO EXCESSIVE RISK OR FAILING TO GET HEALTH CARE AND FINALLY THE IMPORTANCE OF PARENTAL PERMISSION WHICH I'M NOT GOING TO BE TALKING ABOUT EITHER. FOLKS US -- THE FOCUS IS ON THE MIDDLE TWO. LOW RISK PATHWAY, THERE'S NO PERFORMANCE TENSION FOR DIRECT BENEFIT TO THE CHILD, RESTRICT TO MINIMAL RISK OR MINOR INCREASE OVER MINIMAL RISK. THERE'S THE HIGH RISK PATHWAY, IF RISKS EXCEED THIS MINOR INCREASE OVER MINIMAL RISK, THOSE RISKS MUST BE JUSTIFIED BY ANTICIPATED BENEFITS TO THE CHILD WHICH IS THE ARGUMENT IN THAT THIS SHOULD NOTE BE DISADVANTAGED. THE OTHER PHRASE IS THE BALANCE OF RISK AND BENEFIT MUST BE FAVORABLE AS ALTERNATIVE, THE IDEA IF YOU'RE WITHHOLDING KNOWN EFFECTIVE TREATMENT THAT CAN BE NO MORE THAN THIS LOW RISK CATEGORY AND I'LL WALK THROUGH THAT WHEN I GET TO THE DISCUSSION OF CHOICE OF CONTROL GROUP. THERE'S TWO KEY CONCEPTS AT PLAY HERE. FIRST IS THIS PROSPECT OF DIRECT BENEFIT. WHICH I'VE ALREADY SHOWN YOU SORT OF DIVIDES THIS LOW RISK AND HIGH RISK PATHWAY. DEFINING THIS IS AN ESSENTIAL ASPECT OF THE ETHICAL ACCEPTABILITY OF THE INTERVENTIONS INCLUDED IN THE RESEARCH PROTOCOL. I'M USING THE WORD INTERVENTIONS EXPLICITLY, THE IMPORTANT SECOND CONCEPT CALLED COMPONENT ANALYSIS. THE IDEA HERE IS THAT A PROTOCOL IS GOING TO CONTAIN MANY THINGS. YOU'VE GOT POTENTIALLY THERAPEUTIC INTERVENTION, TREATMENT, AND RESEARCH ONLY ENDPOINTS. THE IDEA IS YOU HAVE TO ANALYZE APPROPRIATENESS OF THOSE TWO DIFFERENT INTERVENTIONS SEPARATELY. YOU CAN'T JUST SAY, OH, THE PROTOCOL OFFERS A BENEFIT SO WE'RE GOING TO THROW IN A LOT OF NON-BENEFICIAL RESEARCH ONLY END POINTS. YOU'VE GOT TO ANALYZE THE RISK AND BENEFIT OF THESE DIFFERENT COMPONENTS OF THE PROTOCOL SEPARATELY. LET'S TALK ABOUT MUSCLE BIOPSIES, AT MINIMUM PERFORMED AT BASELINE, STUDY COMPLETION, TO MEASURE EFFECT OF EXPERIMENTAL PRODUCT, AT MINIMUM. THERE MAY BE OTHERS. WE COULD DISCUSS WHETHER THAT'S APPROPRIATE OR NOT. OTHER THAN TO ESTABLISH INITIAL DIAGNOSIS THEY ARE NOT CLINICAL INDICATED FOR DISEASE MANAGEMENT AND DO NOT OFFER PROSPECTS OF DIRECT CLINICAL BENEFIT. IN ADDITION, ANESTHESIA OR PROCEDURAL SEDATION IS REQUIRED FOR BIOPSY, NO MORE THAN A MINOR, IT MUST BE LOW RISK, OTHERWISE PROTOCOL COULD BE REFERRED BY AN IRB FOR FEDERAL PANEL REVIEW. THE NATIONAL COMMISSION CALLED AN ESCAPE HATCH, YOU CAN THINK IT'S WORTH DOING BUT DOESN'T FIT UNDER THREE CATEGORIES I'M TALKING ABOUT, COULD BE REFERRED FOR REVIE AND POTENTIALLY APPROVAL BY FDA COMMISSIONER OR SECOND OF HHS DELEGATING THAT TO ASSISTANT SECRETARY FOR HEALTH. I WON'T GO INTO THAT. THAT'S AN AVENUE. WE HAD TWO QUESTIONS. ONE NOTING, LET'S DISCUSS THE VARIOUS FACTORS WITH PROCEDURAL SEDATION, AND THE OTHER VOTING QUESTION, ASSUMING YOU MINIMIZED THOSE RISKS ARE THERE ONE OR MORE APPROACHES TO PROCEDURAL SEDATION THAT WOULD PRESENT NO MORE THAN MINOR INCREASE OVER MINIMAL RISK. I'LL SHOW YOU THE RESULTS. THE SUBCOMMITTEE GENERALLY AGREED AND WHEN YOU HAVE A NON-VOTING QUESTION YOU HAVE TO USE THE WORD GENERALLY. LIKE A FOCUS GROUP, I CAN'T SAY THAT EVERYONE IN THE ROOM AGREED WITH ALL OF THESE BUT THERE WERE NO DISAGREEMENTS. FIRST OF ALL YOU'VE GOT A HIGH VOLUME CENTER THAT'S GOT EXPERIENCE WITH PEDIATRIC SEDATION. SECOND OF ALL A RIGOROUS SCIENTIFIC JUSTIFICATION OF THE NEED FOR THOSE PROCEDURES. THESE APPROACHES SHOULD BE DESCRIBED IN THE PROTOCOL, YOU'D BE SURPRISED HOW MANY PROTOCOLS THAT SAY IT WILL BE PROVIDED, PERIOD, DOESN'T DO ANYTHING. WE GIVE THEM THIS LANGUAGE BACK NOW AND SAY NO, PROTOCOL HAS TO DESCRIBE THIS. CHILDREN WITH CHRONIC CONDITIONS AT HIGHER RISK SHOULD BE CAREFULLY EVALUATED AND POTENTIALLY EXCLUDED. CONSIDER KIDS WITH DEVELOPMENTAL DELAY. NON-THERAPEUTIC PROCEDURES SHOULD BE TERMINATED, IF THERE'S COMPLICATIONS, IF YOU'RE DOING A CLINICAL PROCEDURE YOU'LL DO WHATEVER YOU HAVE TO DO TO GET THE RESULT. IF YOU'RE DOING A NON-CLINICAL PROCEDURE FOR RESEARCH ONLY END POINT RUNNING INTO COMPLICATION OF ANESTHETIC YOU SHOULD STOP. THAT'S A DIFFERENT MINDSET. YOU SHOULD STOP. NOW, THE OTHER IS YOU SHOULDN'T AVOID APPROPRIATE SEDATION TO MAKE IT FIT A MINOR INCREASE OVER MINIMUM RISK. IF YOU'RE DOING A PROCEDURE REQUIRING PROCEDURAL SEDATION DON'T NOT DO IT IN ORDER TO FIT IT INTO THE RISK CATEGORY. THAT'S BASICALLY ADDING INSULT TO INJURY OR I GUESS ADDING INJURY TO INSULT UNDER THOSE CIRCUMSTANCES. THEN OF COURSE CLEAR COMMUNICATION TO THE POTENTIAL SUBJECTS AND PARENTS ABOUT WHAT'S GOING ON PARTICULARLY ABOUT NON-THERAPEUTIC NATURE OF THE PROCEED PROCEDURES. WE WENT TO THE SECOND QUESTION. WERE THERE APPROACHES TO PROCEDURE SEDATION APPROVED UNDER MINOR INCREASE OVER MINIMAL RISK? WE ENDED UP WITH A HUNG JURY. YES, SEVEN. NO, NINE. THIS WAS A GROUP OF ETHICISTS AND PEDIATRIC ANESTHETISTS, SPLIT ALL OVER THE PLACE. BASICALLY THEY WEREN'T ABLE TO AGREE. THAT'S WHY AT THIS POINT WE GENERALLY TAKE A PROCEDURAL APPROACH. AND HERE IS THE REASONS. I WON'T GO THROUGH THOSE BUT THOSE WHO VOTED YES SAID THERE WOULD BE CIRCUMSTANCES YOU COULD POTENTIALLY DO THIS. THOSE THAT VOTED NO WERE CONCERNED THAT IN FACT THIS WAS SORT OF A CAMEL'S NOSE WITHIN THE TENT, HARD TO CONTROL. THE AMERICAN ACADEMY CAME OUT WITH A GUIDELINE, IN SPITE OF IMPROVEMENTS THERE'S A LOW BUT PERSISTENT RATE OF POTENTIAL SEDATION INDUCED LIFE-THREATENING EVENTS. IT'S RISKY BUSINESS WHEN YOU'RE DOING THIS. IT'S ALSO A SOURCE OF ONGOING CONTROVERSY. I'VE HAD CONVERSATION WITH SOME IRBs THROUGH E-MAILS. ONE APPROVED UNDER 5052, BASICALLY IGNORING THE BIOPSIES, EFFECTIVELY PUTTING A ROUND PEG INTO A SQUARE HOLE OR THE OPPOSITE. WHY? BECAUSE THEY DIDN'T WANT TO REFER IT FOR FEDERAL REVIEW BECAUSE THERE'S PERCEPTION THAT'S ONEROUS. DYSTROPHIN LEVELS ARE NOT APPROVED. IF IT WAS WE COULD STOP WITHOUT THE CLINICAL ENDPOINT BUT GIVEN RECENT EVENTS IT MAY SERVE AS BASIS FOR ACCELERATED APPROVAL IN TERMS OF REASONABLY LIKELY. MY POINT IS THAT THIS CONTROVERSY SHOULD PROVIDE A SENSE OF SURGERY TO DEVELOP ALTERNATIVE BIOMARKERS THAT DO NOT REQUIRE A SURGICAL PROCEDURE UNDER GENERAL ANESTHESIA. GOOD SCIENCE IS A MORAL OBLIGATION. HERE IS A QUOTE FROM THE LETTER OF DR. CALIFF AVAILABLE ON THE PUBLIC WEBSITE. THE POOR QUALITY OF MANY BIOPSIES AND FAILURE OF SPONSOR TO IMPLEMENT HIGH QUALITY PROCEDURE FOR ASSAY VALIDATION LED TO A SITUATION IN WHICH ONLY A FRACTION OF DATA COULD BE USED TO MAKE THE REGULATORY DECISION. GIVEN THE SERIOUS NATURE OF THE DISEASE AND INVASIVENESS OF PROCEDURE ANY STUDY MUST BE CONDUCTED ACCORDING TO THE HIGHEST STANDARDS, CONFIDENT THEY HAVE CORRECTED AS MUCH AS POSSIBLE TO GENERALIZABLE KNOWLEDGE NEEDED TO PROVIDE EFFECTIVE TREATMENT BASED ON HIGH-QUALITY EVIDENCE. NOBODY COULD DISAGREE WITH THAT STATEMENT. IF WE'RE PUTTING KIDS THROUGH THESE PROCEDURES WE BETTER MAKE SURE WE'RE DOING THE RIGHT THING WITH THOSE BIOPSIES. THERE WERE STORIES ABOUT THEM BEING LOST, NOT BEING PUT INTO THE FREEZER. IT WAS PRETTY DISTURBING. LET'S TALK ABOUT CHOICE OF CONTROL GROUP. VARIOUS CHOICES OF CONTROL GROUP, A PLACEBO CONTROL, MAIN PURPOSE TO MASK TREATMENT ASSIGNMENT. THERE COULD BE A CONCURRENT NO TREATMENT CONTROL WHICH OFTEN WE USE PLACEBO TO MASK ASSIGNMENT, YOU COULD HAVE ADD-ON TRIALS AND ARGUE MOST IF NOT ALL CHILDREN WITH DUCHENNE MUSCULAR DYSTROPHY ARE ON STEROIDS AND EXTERNAL IF THERE'S AN APPROVAL THAT MIGHT HAPPEN SINCE THERE'S AN APPLICATION IN HOUSE I HAVE NO IDEA IF IT WILL OR WILL NOT GET APPROVED. I THINK IT IS, DEFLEXACORT? AN ADD-ON TRIAL MAY BE WHAT EVERYBODY IS GOING TO BE DOING. DOSE-RESPONSE DESIGN, YOU NEED SEPARATION BETWEEN DOSES, HIGH AND LOW DOSE, THAT'S THE DESIGN IN THE POST MARKETING REQUIREMENT FOR SEREPTA. ACTIVE TREATMENT CONTROL IS ALSO POSSIBILITY WITH NON-INFERIORITY DESIGN, ALWAYS CHALLENGING BECAUSE YOU NEED A PREVIOUS PLACEBO CONTROL DESIGN TO SET NON-INFERIOR, SUPERIORITY HAS TO HAVE CONFIDENCE TO BEAT EXTRA TREATMENT. AND EXTERNAL CONTROLS, A RETROSPECTIVE OR PROSPECTIVE NATURAL HISTORY CONTROL WHICH HAS BENEFIT IF YOU'RE DOING PROSPECTIVELY TO INCLUDE SAME MEASURES YOU NIGHT INCLUDE IN YOUR CLINICAL TRIALS. THOSE ARE ALL OPTIONS. LET ME TALK SPECIFICALLY ABOUT ISSUES WITH PLACEBO OR SHAM CONTROLS IN PEDIATRICS. NOW, PLACEBO DOESN'T OFFER PROSPECT OF DIRECT BENEFIT TO ENROLLED CHILDREN AND PRESENTS TWO TIMES OF RISK, RISK OF THE PLACEBO ITSELF, THIS IS AN ORAL TREATMENT FOR THE PURPOSE OF MASKING TREATMENT ASSIGNMENT, THAT'S USUALLY FAIRLY MINIMAL UNLESS THE TASTE MASKING IS DISGUSTING, MAYBE MORE THAN MINIMAL TO A CHILD. YOU'VE GOT THE RISK OF WITHHOLDING PROVEN OR KNOWN EFFECTIVE TREATMENT WHICH OBVIOUSLY IN SOME MUSCULAR DYSTROPHY, THERE ARE NO KNOWN EFFECTIVE TREATMENTS. BUT SOME DAY THAT MAY IN FACT BE THE CASE. BOTH TIMES OF RISK MUST BE NO GREATER THAN MINOR INCREASE OVER MINIMAL RISK, LONGER CONVERSATION, BUT THIS IS CONSISTENT WITH ICHE 10, THE DOCUMENT IN THE CONTROL GROUP AND 2013 DECLARATION OF HELSINKI. YOU HAVE A CENTRAL CATHETER, IT EXCEEDS THIS LEVEL OF LOW RISK, THUS NOT APPROPRIATE FOR CHILDREN RECEIVING PLACEBO INFUSION ABSENT REFERRAL TO THE FEDERAL PANEL I MENTIONED. DIFFICULTY HERE IF YOU HAVE A BLINDED CLINICAL TRIAL YOU WON'T KNOW WHO GETS THE ACTIVE INTERVENTION, MAYBE ACCEPTABLE FOR THE CHILDREN GETTING IT BUT NOT ACCEPTABLE OVER TIME FOR CHILDREN NOT GETTING THAT INTERVENTION. FDA ACTUALLY PUT A CLINICAL TRIAL OF A DRUG FOR TYPE I DIABETES ON CLINICAL HOLD BECAUSE THEY WERE PLACING SUCH CENTRAL LINES. RANDOMIZATION, NOW A RANDOMIZED CONTROL TRIAL REGARDLESS. CHOICE OF ROLE GROUP SHOULD BE PERFORMED AS EARLY AS POSSIBLE IN THE DEVELOPMENT PROGRAM TO AVOID POTENTIALLY MISLEADING FINDINGS. AS I'VE BEEN CONSULTED ON PEDIATRIC DESIGN ISSUES WHAT STUCK WAS EXTENT TO WHICH THERE ARE PHASE 2 TRIALS DESIGNED AND THEN PEOPLE COME IN BECAUSE THEY SEE A RESULT PERHAPS AGAINST THE NATURAL HISTORY CONTROL WHICH MAY BE POORLY DONE TO SAY THAT THEY OUGHT TO BE APPROVED. I AM BEGINNING TO THINK ONCE WE HAVE DATA AT PHASE 1, GO RIGHT TO PHASE 3, RANDOMIZE EARLY AND GET AN ANSWER EARLY. THAT'S SORT OF WHAT I'M BEGINNING TO THINK IS THE WAY WE SHOULD BE DOING THAT AND PRETTY MUCH MANY, MANY, MANY PEDIATRIC RARE DISEASE PROGRAMS. ABSENT USE OF BIOMARKERS UNDER CLINICAL ENDPOINTS RESISTANT TO MANIPULATION TREATMENT ASSIGNMENT MUST BE MASKED. RESULTS OF THE SIX MINUTE WALK TEST DEPEND UPON THE CHILD'S MOTIVATION BUT THEY CAN ALSO BE MANIPULATED THROUGH COACHING AND TRAINING. DOSE-RESPONSE DESIGN AVOIDS USE OF PLACEBO AND PROBLEM OF LONG-TERM INTRAVENOUS ACCESS ABSENT PROSPECT OF DIRECT BENEFIT, YOU COULD ARGUABLY USE SUCH AN INFUSION BUT THE DIFFERENCE IN THE DOSES MUST BE SUFFICIENT TO SHOW CLEAR SEPARATION BECAUSE YOU COULD END UP ON A PLATEAU OR LOW AND JUST NOT SEE THAT SEPARATION OF DOSE-RESPONSE CONTROL REQUIRES SEPARATION TO BE ABLE TO CONCLUDE THAT IT'S EFFECTIVE. OTHERWISE BOTH COULD BE INEFFECTIVE OR EFFECTIVE BACKUP -- BUT YOU DO NOT KNOW IT. THOUGHTS ON GAMING OR IMPROVING THE SYSTEM MAY BE PROVOCATIVE. CLINICAL TRIALS MAY BE ENRICHED. WE TALKED ABOUT ENRICHMENT DESIGNS WITH CHILDREN THOUGHT HAVE TO HAVE THE BEST CHANCE OF MORE ROBUST RESPONSE TO AN EXPERIMENTAL INTERVENTION TO IMPROVE EFFICIENCY OF CLINICAL TRIAL, WE'VE SEEN THAT IN DUCHENNE CHILDREN LESS SEVERELY AFFECTED EXCLUDED, MORE SEVERELY AFFECTED WILL BE EXCLUDED. CHILDREN LESS SEVERELY AFFECTED SOME PARENTS MAY BE COACHING CHILDREN BECAUSE THEY WANT TO GET ACCESS TO THAT DRUG EVEN IF IT'S A RANDOMIZED PLACEBO CONTROLLED DRUG THEY WANT A SHOT AND TEACH THEM TO SLOW DOWN TO MEET INCLUSION CRITERIA. IF THIS IS MASKED AND COACHING SYMPTOMS PLACEBO GROUP WILL IMPROVE. IF NOT STOPPED ACTIVE INTERVENTION GROUP WILL NOT IMPROVE. EITHER WAY THE TRIAL IS UNDERMINED IN TERMS OF BEING ABLE TO GET AN ANSWER TO THE QUESTION. THE OTHER CONCERN IS CHILDREN MORE SEVERELY AFFECTED MAY BE EXCLUDED GIVEN INABILITY TO PERFORM REQUIRED OUTCOME MEASURE, THE SIX-MINUTE WALK TEST, THERE'S NOT A LOT OF FANS OF THAT ENDPOINT BUT THERE'S TREATMENT IF THEY CAN MAINTAIN UPPER EXTREMITY FUNCTION. WORK THE WHEELCHAIR, PLAY XBOX, PLAY CALL OF DUTY, WHATEVER. WHAT ABOUT IMPROVING THE SYSTEM? THERE MAY BE OTHER REMARKS. FIRST SHARE EXISTING CLINICAL DATA INCLUDING NATURAL HISTORY DATA TO DEVELOP A DISEASE PROGRESSION MOD TOLL SUPPORT FUTURE PRODUCT DEVELOPMENT, CLINICAL PATH INITIATIVE, MANY PEOPLE HERE ARE KNOWLEDGEABLE OF. IT'S IMPORTANT TO SUPPORT THAT DEVELOPMENT THAT REALLY IS DEVELOPING THIS NATURAL HISTORY DATABASE BUT USING EXISTING CLINICAL DATA BUT ALSO CLINICAL DATA FROM TRIALS. DEVELOP MEANINGFUL CLINICAL ENDPOINTS THAT DO NOT REQUIRE WALKING, MORE RESISTANT TO COACHING. WE'RE INVOLVED IN A PROJECT FOR EXAMPLE TRYING TO DEVELOP VALIDATE ACTIGRAPHY, COMPARED TO THOSE WITH PULMONARY HYPERTENSION TO TAKE THAT ACTIGRAPHY, A FIT BIT OR A PRODUCT, I DON'T OWN STOCK OR OWN ONE, SO YOU COULD STUDY HYPERTENSION IN CHILDREN THAT CAN'T WALK. MAYBE SOME OF THOSE TECHNIQUES COULD BE APPLIED. RELIABLE NON-INVASIVE BIO, MAKERS THAT DO NOT REQUIRE SURGERY OR GENERAL ANESTHESIA, ALLOW FOR EARLIER ENROLLMENT, IF YOU CAME TO TIME TO EVENT IN A CHILD AMBULATORY, YOU COULD CROSS TO ACTIVE TREATMENT IF YOU REACHED AN ENDPOINT SUFFICIENTLY SENSITIVE TO SAY THEY HAVE, QUOTE, FAILED TREATMENT BEYOND LOSING ABILITY TO WALK. EXPANDING INCLUSION CRITERIA TO INCLUDE LESS OR MORE AFFECTED CHILDREN OR OTHER ALTERNATIVE TO PERHAPS REDUCE DESIRE TO GET ACCESS BY COACHING OR GAMING THE SYSTEM, DEVELOPING EXPANDED ACCESS PROGRAMS FOR CHILDREN NOT ELIGIBLE FOR THE OUR NEXT PRESENTER IS PAT FURLONG, FOUNDING PRESIDENT AND CEO OF PARENT PROJECT MUSCULAR DYSTROPHY, ACTIVE SINCE OUR INCEPTION, SOMETHING TO DO WITH THE INCEPTION, DISCUSSION OF CLINICAL TRIAL DESIGN FROM PERSPECTIVES OF PATIENT CENTERED BENEFIT/RISK AND PARTICIPANT BURDEN. >> I'M GOING TO BUILD ON WHAT JOHN PORTER TALKED ABOUT AND WHAT SKIP TALKED ABOUT, EXPLORING THE VALUE OF PATIENT AND CARE BEGIN PREFERENCE, BENEFIT, RISK. CHILDREN ARE NOT RESEARCH SUBJECTS, THEY ARE REALLY CHILDREN. PARENTS, AND BY DEFAULT CHILDREN, ARE WILLING TO ACCEPT RISKS WHICH WE'LL LEARN ABOUT. PARENTS LOOK AT INFORMED CONSENT AS A TICKET IN, A RIDE ON THE MERRY-GO-ROUND WITH A CHANCE AT THE BRASS RING BECAUSE THEY HAVE BEEN EXPOSED TO RESEARCH GOING ON, RESEARCH THAT'S EXCITING AND REPETITIVE, THEY HAVE SEEN IT GROW, A BODY OF RESEARCH OVER A PERIOD OF YEARS. BY THE TIME THEY GET TO THE CLINICAL TRIAL IT'S NO LONGER RESEARCH. IT'S TREATMENT FOR THEM. THAT'S A WAY TO GET ACCESS. THE BURDEN ON THE CHILD IN PARTICIPATION IN TRIALS AND BURDEN ON THE FAMILIES IS SIGNIFICANT. TO SET THE STAGE, DUCHENNE, ONE IN 4600 BOYS ARE BORN WITH IT, ONE IN 4600 WOMEN WILL CARRY THAT GENETIC MUTATION AS A NEW EVENT, THEY WILL BECOME NEW CARRIERS, AS I WAS, WITH NO FAMILY HISTORY OF THE DISEASE AT ALL. THE DIAGNOSIS IS STILL BETWEEN 3 AND 5 YEARS OLD, FOLLOWS A PREDICTABLE COURSE, 100% FATAL. THE BASIC FUNDAMENTAL DEFECT IS LOSS OF SKELETAL MUSCLE PROTEIN, DYSTROPHIN, WITHOUT IT LINKING TO THE MEMBRANE, THINGS HAPPEN IN TERMS OF THE MUSCLE JUST CAN'T SURVIVE, INFLUX OF CALCIUM, MUSCLE CELL DIES, FUNCTION IS LOST IN THESE KIDS. I STARTED PPMD IN 1994, HAD A CURIOUS HISTORY TO START THAT ORGANIZATION AFTER LOSING MY SON TO DUCHENNE MUSCULAR DYSTROPHY MUCH RIGHT THEN WHEN WE STARTED AND CAME TO THE WASHINGTON, ONE OF ACTUALLY THE WEEK AFTER MY SONS WERE DIAGNOSED I CAME TO THE NIH AND MET WITH VARIOUS HEADS OF THE NIH AT THE TIME WHERE THE RARE DISEASE LEGISLATION WAS JUST BECOMING WITH ANDY MYERS AND OTHER THAN THAT THE NIH RESPONSE TO RARE DISEASE WAS NOT US, NOT NOW, NOT VERY MUCH MONEY. SO IT REALLY WAS DISASTROUS FOR ME AS A MOTHER TO UNDERSTAND THERE WAS VERY LITTLE INVESTMENT HERE. THE POTENTIAL FOR TREATING THE DISEASE DURING MY SON'S LIFETIME WERE STEROIDS, CHRONIC STEROIDS IN CLINICAL TRIALS, AND AT THE TIME MY CHILDREN WENT TO NATIONWIDE CHILDREN'S, AND THE CLINICAL TRIAL WAS ACCEPTING CHILDREN WITH DUCHENNE, MY ONE SON FIT PROTOCOL, OTHER SON DID NOT. YOU CAN IMAGINE I DIDN'T JOIN THAT STUDY. SO WHAT CHANGED THIS AND WHAT GALVANIZED THIS AND WHAT WE'RE THANKFUL ABOUT IS THE MUSCULAR DYSTROPHY CARE ACT. THIS IS A PIECE OF LEGISLATION THAT WAS SIGNED INTO LAW IN 2001 BY GEORGE BUSH, EVEN IF YOU DON'T LIKE GEORGE BUSH THIS WAS PROBABLY THE BEST THING IN THE WHOLE WORLD FOR DUCHENNE MUSCULAR DYSTROPHY AND ALL THE MUSCULAR DYSTROPHIES, AND TO DATE IT'S GOTTEN ABOUT A HALF A BILLION DOLLAR INVESTMENT ACROSS THE MUSCULAR DYSTROPHIES AND GROWING. TO THAT WE HAVE TO THANK YOU FOR OUR PROGRESS, AND FOR GALVANIZING THIS FIELD, FOR GETTING PEOPLE TO COME TOGETHER AND GETTING SPONSORS TO BE INTERESTED. NOW THE TOTAL NIH SPENDING IS OVER $500 MILLION, 18 NEW DRUGS IN DUCHENNE TRIALS, 22 OTHERS IN CLINICAL DEVELOPMENT, CARE GUIDELINES UPDATED GOING THROUGH CLEARANCE, AND NATURAL HISTORY STUDIES AND REGISTRIES AND DEVELOPMENT TOOLS IN PROGRESS SO WE'RE THRILLED. DUCHENNE IS FAIRLY WELL CHARACTERIZED, BROADLY CHARACTERIZED. WHAT WE DON'T KNOW IS ALL OF THOSE THINGS THAT MODIFY THOSE GENETIC MODIFIERS, WE'RE LEARNING ONE BY ONE BY ONE THAT THERE ARE THINGS THAT MODIFY THE DISEASE AND WOULD BE ABLE TO BETTER PREDICT WHAT A CHILD WILL DO IN TERMS OF PROGRESSION. CLINICAL TRIALS PIPELINE IS FULL. WHAT WE WANTED TO LEARN IS PATIENT VOICE, AS JOHN MENTIONED IN PDUFA 5, IT'S HOPEFULLY HERE TO STAY, NO MATTER EVEN WITH THE NEW ADMINISTRATION WE'RE HOPING IT BECOMES EVEN MORE ROBUST THAN IT IS TODAY. WE THINK THAT AN ORGANIZED VOICE OF THE PATIENT IS NECESSARY AND CENTRAL FOR CHANGE. SO WE WANTED TO UNDERSTAND FROM THE CAREGIVERS, WHAT WAS MOST IMPORTANT TO THEM? WHAT WAS MEANINGFUL IN THEIR LIVES? ND WE WANTED TO DO A PILOT STUDY AND BASICALLY THERE WAS A TIME AND WE'VE BEEN MEETING WITH THE FDA DIVISION OF NEUROLOGY PRODUCTS SINCE 2006, WE FIRST WENT TO THEM TO REALLY TALK ABOUT UNMET NEED AND SAY IT'S HARD FOR ANYONE WHO DOESN'T LIVE WITH A DEGENERATIVE DISEASE EVERY DAY TO UNDERSTAND WHAT THAT MEANS TO THEIR LIFE, THE LIFE OF THE PERSON WHO HAS THE DISEASE AND RIPPLE EFFECT ACROSS THE FAMILY. I HEARD IN THE BACKGROUND A NUMBER OF PEOPLE TALKING, SOMEONE SAID YOU CAN'T HAVE TEN WOMEN CRYING IN THE CORNER. I SAID EXACTLY RIGHT. YOU CAN'T HAVE TEN WOMEN CRYING IN A CORNER AND MAKE SENSE OF IT BUT YOU COULD QUANTIFY THE TEARS AND USE THAT QUANTIFICATION OF THE TEARS TO LOOK AT THEIR BENEFIT AND WHAT MEANS MOST TO THOSE PEOPLE. SO WE FIRST KIND OF ASKED PEOPLE TO TELL US THEIR STORY SO YOU CAN HEAR IN THE PERSPECTIVE WHEN IT COMES TO TERMINAL ILLNESSES THE FDA'S JOB SHOULD BE TO MAKE SURE THE PRODUCT IS SAFE, AND THE RISKS AND BENEFITS PRESENTED BY THE PRODUCER ARE ACCURATE. OUR JOB AS PARENTS IS TO DETERMINE GIVEN ALL THAT INFORMATION WHETHER TO GIVE IT TO OUR CHILDREN, IT'S AN INTENSITY PERSONAL DECISION INVOLVING THE PART AND CHILD WITH DUCHENNE. WE WANTED TO DO A CAREGIVER SURVEY. THIS IS WHERE THERESA MULLINS GROUP DEVELOPED A FRAMED WORK OF BENEFIT/RISK, SOMETHING MEANINGFUL AND RIGOROUS, AND INTERPRETABLE TO THE FDA. WE WANTED TO DO A PATIENT-CENTERED DRUG DEVELOPMENT SURVEY, TO LOOK AT TREATMENT PREFERENCES, WE ENLISTED THE AID OF JOHNS HOPKINS AND RTI, PPMD AT THE TIME FOR HOLLY, LOOKING AT BENEFIT/RISK, COMMUNITY CENTERED RESEARCH TO LOOK AT COMMUNITY AND GET A BROAD AND DIVERSE GROUP OF PEOPLE TO CONNECT WITH US. WE WANTED TO REALLY MAKE SURE THAT THIS FIT THE CRITERIA AND EXISTING FRAMEWORK FOR BENEFIT RISK. WE CREATED WITH A GROUP OF FAMILIES THE TREATMENT FEATURES, ATTRIBUTES, SIX WERE DEVELOPED, USED IN EXPERIMENTAL DESIGN. THESE ARE THE ATTRIBUTES. EFFECT ON MUSCLE FUNCTION, NONE, SLOWS OR STOPS MUSCLE DECLINE. GAIN IN EXPECTED LIFESPAN, NO GAIN, 2 YEARS OR 5 YEARS. POST-APPROVAL INFORMATION, WE WANTED TO KNOW IF THAT WAS IMPORTANT, IF SOME WAS IMPORTANT OR A LOT OF IT. WE WANTED TO LOOK AT WHAT RISKS THEY WOULD BE WILLING TO TALK, NAUSEA, LOSS OF APPETITE, VOMITING, IS THAT ACCEPTABLE IF THERE'S CHANGE. WE WANTED TO LOOK AT RISK OF BLEEDS. AND THAT WAS REALLY IMPORTANT BECAUSE WE HAD AN EXPERIENCE WITH ANOTHER COMPOUND THAT HAD SOME GUM BLEEDS AND THE TRIAL WAS HALTED, PARENTS WERE SORT OF UPSET THAT THE TRIAL WAS HALTED SO WE WANTED TO TALK ABOUT THAT. WE DID USE THE WORD HEMORRHAGE BECAUSE WHILE WE KNEW THAT WAS A WORD THAT PERHAPS SOME FAMILIES WOULDN'T UNDERSTAND THEY WOULDN'T LIKE THAT IDEA OF THE HEMORRHAGE, IT SOUNDED LIKE A SERIOUS CONDITION. WE USED RISK OF HEART ARRHYTHMIA. WE WANTED TO LOOK AT NONE OR RISK OF HARMLESS ARRHYTHMIA OR RISK OF MORE DANGEROUS ARRHYTHMIA. WE PUBLISHED THIS IN A PAPER THAT I SENT AROUND AND I DON'T THINK EVERYONE HAS RECEIVED IT BUT I'M HAPPY TO DELIVER IT, ON BENEFIT-RISK, AND VALIDATE THIS WORK AND MAKE SURE THAT IT WOULD BE SUITABLE, INTERPRETABLE BY THE FDA. THE BENEFIT-RISK STUDY WAS A PILOT STUDY OF 11 CLINICIANS, 115 PARENTS, ALL PARENTS WERE CAUCASIANS, HAD MEAN LEVEL OF EDUCATION THAT WAS COLLEGE EDUCATED, PEOPLE THAT WERE IMMEDIATELY ACCESSIBLE TO US THROUGH OUR REGISTRY, OUR DUCHENNE CONNECT REGISTRY AND SOCIAL MEDIA. WE KNEW WE HAD A SUBSET OF PEOPLE THAT PERHAPS WAS NOT REPRESENTATIVE OF THE DIVERSE POPULATION. THE CLINICIANS FELT RESPONSIBLE TO BALANCE CONSENT WITH HOPE. THEY FELT THEY HAD MORE INFLUENCE ON WHAT THE PARENTAL DECISIONS WOULD BE THAN THE PARENTS FELT THEY DID. WE USED, AGAIN, WITH JOHNS HOPKINS THE BEST/WORST SCALING. PARENTS WHO TOOK THE SURVEY SAID THEY HAD TO SPEND 45 MINUTES WORKING ON THIS TO REALLY THINK THROUGH SOME OF THE QUESTIONS THAT THEY WERE BEING ASKED. SO THIS WAS AN EXAMPLE, SYMPTOMS THE PROGRESSION OF WEAKNESS, NO EXTRA GAIN IN LIFESPAN, YEAR OF POST APPROVAL DRUG, LOSS OF APPETITE, BLEEDING IN GUMS, NO INCREASED RISK OF ARRHYTHMIA, YOU CAN SEE 78% OF THE PEOPLE SAID YES, THEY WOULD TAKE THIS DRUG. THIS IS THE RESULTS. YOU CAN SEE BY THE SCALE HERE THAT THE HIGHEST PRIORITY OF THIS PATIENT, THIS PILOT, WAS SLOWING DISEASE PROGRESSION, HIGHER THAN EXTENDING LIFE YEARS, IT WAS -- AND THESE FAMILIES DIDN'T CONSIDER POST MARKETING ANY MORE ESSENTIAL, SLOWS OR STOPS PROGRESSION OF THE ILLNESS WAS THE HIGHEST PRIORITY OF THE PARENT. SO, THEY WERE WILLING TO TAKE ON RISK. IN FACT, MOST SAID WE TAKE ON RISK WITH THE DIAGNOSIS. WE SIT DOWN AND LISTEN TO WHAT'S LIKELY TO HAPPEN TO OUR CHILDREN IN WHAT PERIOD OF TIME AND WE FEEL WE CARRY SIGNIFICANT RISK ANYWAY. NAUSEA IS NOT SOMETHING THEY WOULDN'T LIVE -- OR SOMETHING THEY COULD LIVE WITHOUT -- COULD LIVE WITH, SORRY. AND THEY DIDN'T REALLY CARE ABOUT THE POST-MARKETING DATA WHATSOEVER. THE NEXT STEPS, WHAT WE'RE DOING NOW, WHAT WE CALLED INTERNALLY BENEFIT/RISK 2.0, THE FDA REQUESTED THAT WE DO A MORE DIVERSE POPULATION, WHICH IS UNDERSTANDABLE. THEY ALSO REQUESTED THAT WE COMPARE THE CAREGIVER PREFERENCES TO THE ADULTS, YOUNG ADULTS WITH DUCHENNE TO SEE IF THE STUDIES ARE THE SAME ARE DIFFERENT, IF THE BOYS AND THEIR PARENTS EXACTLY ALIGNED AND WE'RE GUESSING THAT THEY PROBABLY DON'T ALIGN. WE ALSO WANT TO LEARN, THIS IS BY REQUEST OF THE FDA AND OURS AS WELL, IF THE BENEFIT RISK CHANGES, IF THE BOY OR YOUNG MAN LOSES MORE FUNCTION IS HE MORE OR LESS WILLING TO TAKE ON RISK. SO THAT'S UNDERWAY. WE'RE WORKING WITH SIEBER, THERE ARE COMPANIES AND INDIVIDUAL INVESTIGATORS LOOKING AT GENE THERAPY, WE'RE HOPING TO SEE IN 2017 PILOTS AND TRIALS, THE COMMUNITY IS LOOKING FORWARD TO SEEING THOSE AS WELL. WE WANT TO UNDERSTAND HOW MUCH DO YOU KNOW ABOUT GENE THERAPY AND WHAT ARE THE BENEFITS AND RISKS YOU'RE WILLING TO TAKE ON. WE'RE WORKING IN PARTNERSHIP WITH SIEBER TO EXPLORE BENEFIT RISK AND ANOTHER DAY WE'LL BE ABLE TO HAVE RESULTS. WE'LL DEVELOPING ATTRIBUTES AND SCALING MODELS. WE LOOK AT THERAPEUTIC MISCONCEPTION. ONE OF OUR QUESTIONS IS WHERE DOES IT BEGIN? WHERE DOES IT BEGIN, BECAUSE I'VE BEEN IN LOTS OF CONFERENCES OVER THOSE YEARS AND ONE CONFERENCE I CAN TALK TO YOU ABOUT IS THAT WE HAD A YOUNG INVESTIGATOR COME OVER AND TALK ABOUT OLIGONUCLEOTIDES, A 65-YEAR-OLD PLAYING TENNIS, SAID THAT PERSON HAS MUSCULAR DYSTROPHY BUT THEY ARE DOING -- THEY ARE SKIPPING, SO THAT IS WHERE WE'RE GOING. EVERY PARENT IN THE AUDIENCE RAISED THEIR HAND AND SAID, EXACTLY, 65 YEARS OLD AND PLAYING TENNIS, SO PARENTS ARE EXPOSED TO THE BIOLOGY HERE AND TO SCIENTIFIC PROGRESS. WE COME TO MEETINGS AND SEE YEAR AFTER YEAR AFTER YEAR SOMEONE TALKING ABOUT FOR INSTANCE OLIGONUCLEOTIDES OR GENE THERAPY OR NOW CRISPR AND JOIN THAT CHURCH BECAUSE THE MORE WE HEAR THIS EVOLVE, IF IT WENT AWAY WE WOULD ASSUME IT DIDN'T WORK, RIGHT? BUT THE MORE WE'RE INTO THAT SCIENTIFIC ENVIRONMENT, THE MORE WE BECOME BELIEVERS BEFORE THE FACT, FOR INSTANCE, AND MAYBE EVEN IN THE CLINICAL SETTING WHERE PHYSICIANS REALLY WANT TO DO THE BEST FOR THEIR PATIENTS, THEY ALSO BECOME BELIEVERS OR HOPERS IN THIS FIELD, AND SO WE AS PARENTS THEN REALLY PERHAPS ALL OF US HAVE A THERAPEUTIC MISCONCEPTION WHEN WE JOIN A TRIAL WANTING THE BEST FOR OUR CHILD, WANTING TO RETURN TO THE LIFE THAT WAS EXPECTED BEFORE THIS DIAGNOSIS OCCURRED. SO WE ALSO WROTE AND COLLECTED ALL THOSE STORIES AND HAD PATIENTS WAITING BECAUSE WE WROTE THIS, WE COLLECTED THESE STORIES, AND PUBLISHED THEM BECAUSE WE THINK THIS BOLSTERS THAT BENEFIT/RISK, PROVIDES MEANINGFUL DATA INTO THE BENEFIT/RISK DATA, NOTHING MORE POWERFUL THAN THE WORDS OF THE FAMILIES WHAT THIS MEANS AND WHAT THEY ARE WILLING TO RISK. SO WHEN IT COMES TO TERMINAL ILLNESS, MAKE SURE A PRODUCT IS SAFE, THE RISK AND BENEFITS PRESENTED BY PRODUCER ARE ACCURATE, WE COME BACK TO THIS STATEMENT THAT SAYS WE AS PARENTS WANT TO BE ABLE TO MAKE THE DECISION THAT'S APPROPRIATE BASED ON THE KNOWLEDGE OF SAFETY AND EFFICACY THAT'S AVAILABLE, WE WANT TO HOLD THAT DECISION, IT'S INTENSITY PERSONAL. CLINICAL BENEFIT VERSUS MEANINGFUL BENEFIT, MY HUSBAND IS A PHYSICIAN, HE TELLS ME HOW HIS PATIENTS ARE DOING. I SAY DID YOU ASK THEM? I THINK THIS IS REALLY, REALLY IMPORTANT, AND BEING IN A NURSING FIELD ALL OF MY LIFE, I THINK THAT IT'S REALLY IMPORTANT TO KNOW WHAT MAKES A DIFFERENCE TO PATIENTS, WHAT'S GOING TO CHANGE THEIR LIVES, WHAT'S GOING TO BE MEANINGFUL TO THEM, NOT NECESSARILY TO THE PHYSICIAN, SO WE LOOKED AT HOW DOES IT TRANSLATE 6-MINUTE WORK, STAIR CLIMB, LIFE CLIMB INTO MEANINGFUL BENEFITS, SLOW/HALT PROGRESSION, WALK/STAND, SELF-FIELD, TOUCH HEAD, TOUCH SOMEONE YOU LOVE, SOMETHING THEY ARE INTERESTED IN REPORTING ABOUT. NOW I'M GOING TO SWITCH AND TALK ABOUT WHAT WE'RE LEARNING ABOUT PARTICIPATING IN CLINICAL TRIALS. CLINICAL TRIALS ARE HARD, RIGHT? IT'S YOUR CHANCE AT SOMETHING THAT MIGHT SLOW DISEASE PROGRESSION, HIGHEST PRIORITY AND BENEFIT/RISK BUT ALSO HARD. SIGNING INFORMED CONSENT DOESN'T NECESSARILY CLUE YOU IN TO WHAT HAPPENS IN A CLINICAL TRIAL. ONE OF THE MOMS SAID I SIGNED THE CONSENT FORM BUT DIDN'T KNOW THAT WOULD MEAN ON WEEK 20 LAYING ACROSS MY CHILD WHILE THEY DREW BLOOD. IT'S THE PHYSICAL REALITY OF WHAT HAPPENS IN A TRIAL. SO WHEN YOU'RE A PATIENT, TREATED WITH URGENCY, SOMETIMES IN A CLINICAL TRIAL THAT FEELS DIFFERENT. YOU'RE A SUBJECT. IT'S JUST I HAVE TO GET THESE TESTS DONE. AND THERE IS NO URGENCY, AT LEAST THE PATIENTS FELT THERE WAS NO URGENCY. AND I THOUGHT ONCE KIDS HAD GIVEN THE POUND OF FLESH THERE WOULD BE A SENSE OF OBLIGATION. PATIENTS ASKED FOR INDIVIDUAL DATA, WHAT HAPPENED TO MY SON IN THIS TRIAL AND NEVER GOTTEN IT AND NEVER UNDERSTOOD WHAT HAPPENED. SO THIS AGAIN, NOBODY CAN PREPARE YOU FOR THE ROLLER COASTER OF EMOTIONS YOUR FAMILY WILL RIDE WHEN YOU SIGN UP FOR THE TRIAL. THAT WE'RE ON AN EMOTIONAL ROLLER COASTER WAITING FOR EACH SHOE TO DROP AND THEY ELEVATES THAT AND CAUSES THE DOWNHILL SLIDES TO BE PRETTY SIGNIFICANT AS WELL. SO, I DIDN'T CONSIDER THE FACT THAT WE WERE MEDICALIZING MY SON'S LIFE. SO EVERYTHING, AND WE'VE TALKED TO ONCOLOGY GROUP AND THEY SAID IN ONCOLOGY YOU SAY TO THE FAMILIES, WE GIVE YOU A YEAR OF OUR LIFE AND WE'LL KNOW SOMETHING. IN DUCHENNE, YOU'RE GOING TO KNOW SOMETHING BUT YOU STILL HAVE DUCHENNE AND SO IT'S GOING TO CONTINUE ITS PROGRESSION, SO YOU MEDICALIZE THESE CHILDREN'S LIVES. IN FACT, I HAD A FATHER CALL ME WHO WAS IN A STUDY, HE SAID MY SON HAS JUST DETERIORATED, HE STARTED BITING PEOPLE AT SCHOOL AND BITING US, DIDN'T COME TO DINNER, HE SAID WHAT WOULD YOU DO? I SAID I DON'T KNOW. I'M NOT EQUIPPED BUT I SAID I THINK I WOULD FIRST SIT DOWN ON THE -- WHEN HE WENT TO BED AND START CRYING AND SAY I DON'T KNOW WHAT TO DO TO HELP YOU. HE DID THAT. HIS SON SAID TO HIM, I WAS DIFFERENT IN SCHOOL, EVERYBODY LIKED ME. THEY KNEW I WAS A LITTLE DIFFERENT, I COULDN'T KEEP UP. THEN I WENT TO THIS CLINICAL TRIAL, AND I TOLD THEM I WAS GOING TO GET MAGIC MEDICINE. NOW I'M MORE DIFFERENT BECAUSE I HAVE TO GO SOMEWHERE FREQUENTLY TO GET THIS INTERVENTION, WHICH IS MAKING ME MORE DIFFERENT THAN LESS DIFFERENT. HE ASKED TO QUIT THE STUDY. HIS FATHER SAID NO. I DIDN'T EXPECT ALL OF THE LOGISTICS THAT WOULD BE ADDED TO OUR LIVES, LIKE HAVING ANOTHER PART-TIME JOB, JUST TO FULFILL THAT REQUIREMENT. I UNDERESTIMATED THE TOLL IT WOULD TAKE ON EVERYBODY ELSE IN MY FAMILY. SO THIS IS REALLY -- IT HAS A RIPPLE EFFECT ACROSS FAMILIES. VERY MUCH ACROSS FAMILIES. THIS IS JUST ONE EXAMPLE OF THE MOM WHO SPENT 28 NIGHTS IN A HOSPITAL, 52 DAYS AS INPATIENT, GAVE BLOOD, URINE, SWEAT, TEARS, ACCESS TO EVERY PART OF HER SON'S BODY AND HIS LIFE. THEY COMPLIED WITH EVERY TEST AND MEASURE WITH MILITARY PRECISION. THEY STOPPED HIM DRINKING AND EATING THINGS HE LOVE, FOODS THAT GAVE HIM PLEASURE AND MADE HIM ENJOY HIS LIFE. THAT WAS PART OF A CHILD'S EXPERIENCE IN THE CLINICAL TRIAL. THE COST OF PARTICIPATION, PHYSICAL COST, OFTEN THE SPONSOR PAYS FOR TRAVEL BUT THE TRAVEL AND HOTEL IS ONE THESE. THREE MONTHS TRIAL TURNS INTO FIVE MONTHS, CHANGED FAMILY DIETS, SACRIFICED HOLIDAY, CUT BACK ON LUXURIES, LOSS OF EARNINGS, THREAT OF LOSS OF INSURANCE BECAUSE SHE WAS QUITTING HER JOB AND THE HUSBAND COULDN'T TAKE OVER. AND THEN THE MANY BRIBES. I DON'T KNOW ABOUT YOU HAVE YOU I BRIBE THEM, I HAVE 42-YEAR-OLD DAUGHTERS I STILL BRIBE TO BRING MY GRANDDAUGHTER HOME FREQUENTLY. WE BRIBE OUR CHILDREN BUT IN A CLINICAL TRIAL IT'S EXPENSIVE BRIBES THAT YOU DO ON A WEEKLY OR MONTHLY BASIS, JUST TO GET COMPLIANCE IN THE STUDY. SO IT'S REALLY HARD TO PARTICIPATE IN TRIALS. THE FINANCIAL BURDEN, SOMETIMES FIVE OR SIX THOUSAND DOLLARS WORTH OF TOYS OR CHANGES OR BABY-SITTING OR SOMETHING. NEVER MIND THE FACT THAT PARENTS WITHOUT RESOURCES MAYBE WON'T HAVE A CREDIT CARD. THEY CAN'T BEAR THAT TRAVEL FOR REIMBURSEMENT NOR COULD THEY PAY THE FEES THAT ARE CHARGED FOR A DELAYED TRIP TO THAT CREDIT CARD COMPANY. SO THE UNCERTAINTY OF THE TRIAL, LAYING IN A BED, KNOWING YOUR CHILD TOOK A DRUG THAT'S NEVER BEEN IN SOMEBODY BEFORE. ARE THEY GOING TO STILL BREATHE THEY END OF THE DAY? ARE THEY GOING TO BE WITH YOU? ARE THEY GOING TO LOOK DIFFERENT, BE DIFFERENT, LOSE OR GAIN FUNCTION? THE FIRST CHILD OR FIRST GROUP EXPOSED. SO THESE ARE ALL WORRIES THAT PARENTS HAVE AS THEY PARTICIPATE IN TRIALS. PLACEBO, WE'VE TALKED ABOUT THIS. WHEN YOU KNOW YOUR DISEASE IS GOING TO BE PROGRESSIVE, A PLACEBO FEELS SO BAD, RIGHT? IT FEELS LIKE IT'S DOING HARM. I DON'T DISAGREE WE HAVE TO DO TRIALS THAT REALLY UNDERSTAND THE EFFICACY AND BENEFIT, BUT FOR INSTANCE A TRIAL LIKE -- SOME TRIALS ON A YEAR OR TWO ON PLACEBO AND GET AN INJECTION OR INFUSE EVERY WEEK FEELS DIFFERENT FOR PATIENTS TO MAKE THAT DECISION FOR THEIR SON. I CAN IMAGINE HOW IT WOULD FEEL FOR A LITTLE ONE WHO REALLY WAS STRUGGLING TO BE LIKE HIS FRIENDS. I THINK WE HAVE TO THINK THOROUGHLY AND THOUGHTFULLY ABOUT CHILDREN IN TRIALS AND WHAT WE'RE GOING TO THEM AND HOW WE EDUCATE THEM AND CONSIDER CONSENT ALONG THE WAY. CONSENT AT THE BEGINNING MAY FEEL QUITE DIFFERENT AT THREE OR SIX OR NINE MONTHS OR GOD FORBID TWO YEARS. WE NEED TO THINK THROUGH CONSENT AND KEEP PATIENTS AND FAMILIES INFORMED AND I ALSO THINK THEY NEED PSYCHOLOGICAL SUPPORT DURING THESE STUDIES. IT MUST BE AWFUL IF YOUR SON STARTS BITING EVERYONE AND FALLING APART. DUCHENNE IS HEARTBREAKING ENOUGH WITHOUT THAT. SOCIAL NETWORKING IS AN INTERESTING PLACE, WHERE YOU CAN FIND PEOPLE THAT ARE LIKE YOU, WITH EXPERIENCES LIKE YOURS, YOU CAN LISTEN TO THEMT LEARN FROM THEM, SHARE WITH THEM AND VENT, PROBABLY INAPPROPRIATELY BUT IT'S YOUR SAFE SPACE. FACEBOOK I NEVER WOULD GUESS IS A SAFE SPACE BUT FAMILIES DO. JUST YESTERDAY ONE OF THE MOMS SAID I'M IN A TRIAL, HOW MANY OF YOUR KIDS ARE ON PROZAC? BECAUSE OF THEIR BEHAVIORS. WITHIN 15 MINUTES, 20 WOMEN SIGNED UP AND SAID MINE, MINE, MINE. AND I TOOK OFF WHERE THEY WERE AND WHAT TRIALS THEY WERE IN. SO PHYSICIANS ARE PRESCRIBING PROZAC BECAUSE OF THE BEHAVIOR THAT'S OCCURRING INSIDE A TRIAL. AT THE END OF THE DAY ROLLING WITH THE PUNCHES, THIS JUST IS AN EXAMPLE OF A MOM WHO HAD A CHILD WHO HAD A PORT PLACED, THEY PUT IN THE WRONG PORT, HAD TO GO BACK, GET THE RIGHT SIZE, GO BACK. THEY DIDN'T INFORM HER ABOUT CARE OF HIS PORT AND SHE WAS BACK AND FORTH THREE TIMES WITH THIS SURGICAL PROCEDURE AND GENERAL ANESTHESIA. AND AT THE END OF THE DAY, SHE SAID WE BELIEVE IT'S WORTH IT TO HAVE A CHANCE AT SOMETHING THAT MIGHT BE DIFFERENT AND SLOW PROGRESSION. IT COMES BACK TO BENEFIT/RISK, WILLING TO ASSUME CONSIDERABLE RISK FOR THE POSSIBILITY OF BENEFIT AND THE BENEFIT OF THE HIGHEST PRIORITY IS SLOWING DISEASE PROGRESSION. THANK YOU. [APPLAUSE] >> THANKS VERY MUCH, PAT, AND FOR ALL YOU DO FOR THIS GROUP AND FOR OTHERS ALL OVER. ARE THERE ANY QUESTIONS? WE'LL TAKE SOME QUESTIONS AT THIS POINT. ANN? >> YES. THESE PROTOCOLS, ARE THE PARENTS INVOLVED IN ANY WAY IN A PROTOCOL REVIEW OR COMMENTS ABOUT WHAT IS DOABLE, NOT DOABLE? >> AT PPMD WE'RE WORKING WITH COMPANIES TO BE A PROTOCOLS BUT TYPICALLY HAVE NOT SEEN TO DATE THEY WILL GET A PARENT, YOU KNOW, AGAIN, MUCH OF THE TIME THE AVAILABLE PARENTS ARE 7% GROUP IN FACEBOOK, SO REACHING OUT TO SOMEBODY WHO DOESN'T HAVE A CREDIT CARD, SOMEONE WHO MAY HAVE TO TRAVEL MILES WOULD BE USEFUL. I THINK WE'VE BEEN WORKING WITH COMPANIES AS MDA, AS EVERYONE AROUND THE TABLE, I THINK HAVING A PARENT ON A STEERING COMMITTEE, I THINK THAT COMPANIES NEED PATIENT ENGAGEMENT COMMITTEE, THAT SITS IN ON STEERING COMMITTEES, OBVIOUSLY UNDER CVA, ET CETERA, WILLING TO COMMIT THE TIME. THE OTHER SIDE OF THIS IS WHEN YOU HAVE A CHILD WITH DUCHENNE THERE'S SO MANY ACCOMMODATIONS YOU HAVE TO MAKE THAT SPENDING TIME FLYING HERE TO PARTICIPATE IN A STEERING COMMITTEE IS ALSO HARD. WE HAVE TO FIGURE THAT OUT BETTER AND I AGREE WITH YOU, PATIENTS SHOULD SIT ON STEERING COMMITTEES AND DSMBs. >> DR. WAGNER. >> THANK YOU FOR BRINGING UP THE THERAPEUTIC MISCONCEPTION, THAT'S SOMETHING I SEE A LOT. I'M ALSO VERY MUCH STRUCK BY THERAPEUTIC MISCONCEPTION IN THE CHILDREN THAT DESPITE OUR ATTEMPTS TO GET A SENSE FROM THE CHILDREN, THE VAST MAJORITY THINK THEY ARE GETTING A TREATMENT AND REALLY HAVE NO CONCEPT OF WHAT RESEARCH IS. THAT WAS A RECENT STUDY IN PEDIATRIC ONCOLOGY THAT ECHOED THAT, WHERE THE VAST MAJORITY OF CHILDREN IN PEDIATRIC ONCOLOGY TRIALS BELIEVED IT WAS A TREATMENT AND REALLY DIDN'T UNDERSTAND THAT IT WAS RESEARCH. >> YEAH, KATHERINE, IT'S REALLY, REALLY HARD. I THINK AS A PARENT IT'S REALLY HARD TO EXPLAIN RESEARCH TO A CHILD. I THINK THEY GET IT. IT'S LIKE ME, REALLY. MAYBE I'M JUST A CHILD AND NEVER WILL GROW UP. I CAN TALK ABOUT DUCHENNE ALL DAY, FROM THE DAY MY SONS WERE DIAGNOSED WHEN I WAS IN A VERY OBJECTIVE SETTING, COULD TALK ABOUT DUCHENNE MUSCULAR DYSTROPHY. IN FACT MY SON CHRISTOPHER WAS DYING, RIGHT? THERE WAS NOTHING WE COULD DO. WENT INTO THE LITTLE ROOM AND WE ALL TALKED ABOUT THIS PATIENT. HE WAS A MESS, RIGHT? HE SHOULD HAVE BEEN TRACHED, IN RENAL FAILURE, NOTHING YOU CAN DO. I SIGNED THE PAPERS, THERE WAS NOTHING YOU COULD DO. I WALKED IN THE ICU, WHERE ARE THE ANTIBIOTICS, WHEN ARE WE STARTING RENAL DIALYSIS? BECAUSE THERE'S A LOGICAL PART OF ME THAT UNDERSTOOD HE COULDN'T SURVIVE, RIGHT? BUT THERE WAS THE MOM IN ME THAT SAID HE SHOULD SURVIVE. AND ALL THESE PEOPLE ARE JUST DOCTORS AND THEY ARE CRAZY AND THERE SHOULD BE ONE PERSON IN THE WORLD THAT SURVIVES. IT WAS THE SAME WITH PETER LAW'S STUFF, ON THE SINGLE CHANCE THAT THIS ONE CELL WOULD BE INTEGRATED WITH ANOTHER CELL, I DON'T KNOW HOW YOU EXPLAIN RESEARCH IN SUCH A WAY YOU CAN INCORPORATE IT ACROSS BOTH, THE INTELLECTUAL PERSON WHO UNDERSTANDS WHAT WE'RE DOING AND THE EMOTIONAL PERSON WHO WANTS A DIFFERENCE, CHILDREN MUST STRUGGLE WITH THAT AS WELL. I DON'T KNOW. I THINK IT'S A REALLY -- IT'S REALLY, REALLY HARD, AS A PARENT HOW DO YOU SAY TO YOUR SON WE'RE JUST GOING TO DO THESE THIS CLINICAL TRIAL AND I HOPE IT HELPS SOMEBODY SOMEDAY, THEN I THINK I'D STRUGGLE WITH GETTING HIM TO GET IN THE CAR TO GO. THERE HAS TO BE SOMETHING IN IT FOR THIS CHILD THAT IS NOT JUST ALTRUISTIC AND YOU'RE GOING TO HELP THE FIELD SOMEDAY. >> JUST A COMMENT ABOUT A DISTINCTION THAT I THINK IS USEFUL, BETWEEN THERAPEUTIC MISCONCEPTION AND MISESTIMATION. MISCONCEPTION WAS DEVELOPED AROUND THE IDEA PEOPLE DON'T KNOW THEY ARE ACTUALLY IN RESEARCH WHICH I THINK IS WHAT YOU'RE REFERRING TO OFTEN IN CHILDREN. THEY MIGHT NOT KNOW THEY ARE IN RESEARCH. WHAT'S UNCLEAR IS WHETHER THE PARENTS MIGHT KNOW THEY ARE IN RESERVE BUT HAVE A THERAPEUTIC MISESTIMATION ABOUT THE BENEFITS THEY HOPE TO ACHIEVE AROUND THAT AND SO JUST TO PUT THAT ON THE TABLE FOR -- THINK THAT'S AN IMPORTANT DISTINCTION. SOMEONE COULD EASILY SAY I KNOW I'M IN RESEARCH, BUT I FULLY EXPECT I'M GOING TO HAVE BENEFIT FROM THIS, WHICH WOULD BE A THERAPEUTIC MISESTIMATION, NOT MISCONCEPTION. >> THAT'S PROBABLY MORE LIKE WHAT WE'RE LOOKING AT. >> IN SOME OF THESE, DR. NELSON, SOME OF THESE TRIALS, DO THEY HAVE THIRD PARTIES EXPLAINING BENEFITS AND RISKS RATHER THAN THE INVESTIGATOR EXPLAIN BENEFITS AND RISKS? >> YOU KNOW, BASED ON MY EXPERIENCE IN MY FORMER LIFE AS AN ACADEMIC, I THINK IT'S ALL OVER THE -- I MEAN IT'S HANDLED DIFFERENTLY BY DIFFERENT RESEARCH TEAMS. THERE MAY BE A RESEARCH COORDINATOR THAT GOES IN AND READS THE CONSENT DOCUMENT TO THE PARENT. THERE MAY BE INVESTIGATORS THAT HAVE THAT CONVERSATION. I THINK IT'S QUITE VARIABLE. THE ONLY WORK I KNOW OF THAT'S BEEN DONE CONSISTENTLY AROUND WHAT CONVERSATIONS TAKE PLACE IS THE STUFF THAT RICK KODISH HAS DONE IN ONCOLOGY. IT'S QUITE VARIABLE AND IT'S AN OPEN QUESTION, WHETHER THE ENTHUSIASM OF THE INVESTIGATOR IS TRANSLATED INTO A THERAPEUTIC MISESTIMATION ON THE PART OF THE PARENT AND I SUSPECT THAT THAT'S LIKELY >> THAT'S WHY I BRING IT UP. >> I WILL SAY I'M NOT THAT CRITICAL OF A THERAPEUTIC MISESTIMATION, BECAUSE HAVING BEEN IN INTENSIVE CARE, PARENTS ALWAYS HOPE FOR THE BEST. I THINK IT'S A MISCONCEPTION THAT'S PROBLEMATIC. IT DOESN'T BOTHER ME IF A PARENT KNOWS THEY ARE IN RESEARCH, UNDERSTANDS THEY COULD BE RANDOMIZED TO PLACEBO, I'M NOT AS CONCERNED ETHICALLY ABOUT THE MISESTIMATION AS I AM AROUND THE MISCONCEPTION BECAUSE I MEAN I WAS NEVER ABLE TO SQUELCH HOPE AS A PHYSICIAN IN INTENSIVE CARE UNIT. I COULD NEVER DO THAT EVEN IN THE MOST DIRE CIRCUMSTANCES. >> SHARON AND THEN KATHY SPONG. >> SO, I HAVE KIND OF AN INTERESTING PERSPECTIVE HOW DO WE BETTER SUPPORT FAMILIES IN TRIALS AND INCORPORATE, YOU KNOW, PEOPLE'S PREFERENCES FOR TRIALS AND SINCE I'VE BEEN ON BOTH SIDES, BOTH IN THE PATIENT COMMUNITY SIDE AND NOW ON BIG PHARMA, WHAT I'M FINDING IS IT'S REALLY HARD TO CONVINCE COMPANIES THAT THIS IS MEANINGFUL, LIKE THEY THINK IT'S THE RIGHT THING TO DO TO INCLUDE THE VOICE OF THE PATIENT, BUT WHAT I FEEL THEY ARE MISSING IS HOW IT WILL BENEFIT THEIR TRIALS. I THINK WHAT WE AS A COMMUNITY HAVE TO DO IS A BETTER JOB OF COMING UP WITH A WAY TO MEASURE RESULTS, SO EVERYBODY IS TALKING ABOUT VOICE OF THE PATIENT, INCLUDING PATIENT. WE NEED METRICS, THIS ALLOWS US TO DO BETTER TRIALS, GREATER CHANCE OF SUCCESS OR WE DO SHORTER TRIALS, WE'RE NOT MAKING PROTOCOL REVISION, WE'VE CONSULTED PEOPLE ABOUT WHAT'S FEASIBLE IN ADVANCE. SO IF THERE ARE WAYS THAT WE CAN WORK COLLECTIVELY TO DEVELOP SOME WAY TO MEASURE THE BENEFITS IN A MORE CONCRETE WAY, BEYOND JUST SAYING IT'S THE RIGHT THING TO DO, THAT WOULD BE VERY HELPFUL, HELP ME DO MY JOB. >> I PARTICIPATED WITH A PHARMA COMPANY, NOT IN THE SPACE OF DUCHENNE, AS A PAC MEMBER OF PATIENT ENGAGEMENT COMMITTEE AND WE AGREED TO PARTICIPATE FOR A PERIOD OF TWO YEARS, AND SO WHAT I CAN TELL YOU, ONE EXPERIENCE, IS THAT BASED ON HAVING PATIENTS AND OTHERS INVOLVED IN THE STEERING COMMITTEE, THERE WERE FEWER AMENDMENTS, AND SHORTER PERIOD OF TIME, THEY WERE ABLE TO MEET THE RECRUITMENT GOALS THAT COMMUNITY TRUSTED THEM BECAUSE THEY WERE VERY PUBLIC ABOUT WHO WAS ON THAT STEERING COMMITTEE, IN TERMS OF THE PATIENT EXPERIENCE, AND FEWER AMENDMENTS SO THEY FELT LIKE THEY SAVED MILLIONS OF DOLLARS. SO I THINK THAT WE'RE JUST NOW DEVELOPING THOSE FRAMEWORKS. I DON'T THINK WE HAVE THE PERFECT FRAMEWORK, I DON'T THINK WE HAVE THE PERFECT MODEL, BUT I THINK THE MORE WE HAVE EXPERIENCES ABOUT THOSE, AND THIS COMPANY IS PUBLISHING THIS, I THINK THAT THE MORE WE HAVE EXPERIENCE IN THOSE AND THEY CAN MODELS BE ADAPTED. I THINK WE'RE NOT THERE YET BECAUSE THIS PATIENT FOCUSED DRUG DEVELOPMENT, WHEN YOU GET AN ACRONYM IN WASHINGTON THEN IT'S SOMETHING SPECIAL. MAYBE AS IT EVOLVED WE'LL HAVE MODELS, TOOLS AVAILABLE FOR USE THAT ARE ACCEPTABLE AND HAVE METRICS TO THEM ABOUT WHAT OCCURS AND WHAT BENEFITS ARE RECEIVED. >> DR. SPONG. >> KATHY SPONG FROM NICHD. I WANT TO THANK YOU FOR THIS GREAT PRESENTATION AND RICH DISCUSSION. I THINK, YOU KNOW, HOW WE BEST DESIGN THESE TRIALS AND HOW WE BEST INCORPORATE THE FEEDBACK FROM PEOPLE WHO MIGHT PARTICIPATE IS SOMETHING WE'VE BEEN TRYING TO DO FOR QUITE SOME TIME AND I AGREE THAT THE EXPERIENCES THAT HAVE BEEN DESCRIBED, YOU KNOW, WE CAN HAVE IT GO FROM SOMEONE JUST READING A CONSENT, RIGHT, TO SOMEONE REALLY TRYING TO MAKE CERTAIN THAT THE PATIENT, THE FAMILY, THE CHILD, TRULY UNDERSTANDS WHAT THEY ARE GETTING INTO AND WE'VE HAD A NUMBER OF STUDIES AND TRIALS WE HAVE SUPPORTED OVER THE YEARS, TRYING TO REALLY GET AT SOME OF THOSE ISSUES, HOW DO YOU EXPLAIN RESEARCH, HOW DO YOU EXPLAIN EQUIPOISE, IF I KNEW WHAT THE RIGHT ANSWER WAS WE WOULDN'T HAVE THIS TRIAL. WE WOULD JUST DO IT. I DON'T KNOW, IF THIS TREATMENT BETTER OR NOT, ARE THE CONSEQUENCES BETTER OR NOT? SOME OF THE TRIALS THAT WE'VE DONE, YOU KNOW, HAVE BEEN VERY RISK QUESTION. FOR EXAMPLE, TRIALS ON FETAL SURGERY, RIGHT? YOU'RE REALLY DOING A VERY RISKY THING THAT MAY HAVE IMPLICATIONS THAT YOU DON'T THINK ABOUT AT THE MOMENT. IMPLICATIONS FOR THAT CHILD BUT FOR THE MOTHER, RIGHT? SO HOW DO YOU EXPLAIN THIS CONCEPT OF RESEARCH AND REALLY WITH THAT TRIAL WENT INTO A WHOLE TWO-DAY PROCESS OF TRYING TO EXPLAIN WHAT IS RESEARCH, MEETING WITH ENTIRE TEAMS OF INVESTIGATORS TO TRY TO EXPLAIN THAT SO THAT PEOPLE WENT IN UNDERSTANDING EVEN WITHOUT GETTING WHAT WAS THE INTERVENTION, THEY MAY STILL BE GETTING THE BETTER ARM, RIGHT? BUT THAT'S HARD TO EXPLAIN. IT TAKES A LOT OF TIME AND A LOT OF EFFORT, I APPLAUD THIS GROUP TO DISCUSS THIS AND HELP US WORK BETTER AS WE MOVE FORWARD WITH DOING TRIALS. >> ONE OF THE THINGS THAT I'VE THOUGHT ABOUT, AND I DON'T KNOW IF THIS WOULD WORK, YOU KNOW, WE HAVE ALL THESE CONFERENCES WHERE PEOPLE AS YOU'VE SEEN REPORT TODAY, REALLY GET TOGETHER AND TALK ABOUT IMPORTANT ASPECTS. I WONDER IF IN VARIOUS CENTERS PEOPLE LIKELY TO BE SCREENED FOR A PARTICULAR STUDY COULD BE BROUGHT TOGETHER IN A FOCUS GROUP AND HAVE THIS DISCUSSION BEFORE THE CONSENT, BEFORE ANYTHING, JUST THAT HERE IS THIS TRIAL, HERE IS WHAT IT LOOKS LIKE OR EVEN ONLINE TO HAVE THIS DISCUSSION AND THEN SORT OF A ONE PAGE CONSENT, WHAT RESEARCH IS, WHAT YOU'RE CONSENTING TO, POSSIBILITIES IN TERMS OF OUTCOMES. I REMEMBER BACK TO THE DAY OF DIAGNOSIS, AND I REMEMBER, YOU KNOW, I HAD TWO ALSO ALSO BOYS, GENETICS, PULMONARY, ALL THESE PEOPLE, I WALKED OUT THE DOOR, I DON'T KNOW WHO I SAW. I WONDER IF A TRIAL IS SIMILAR. YOU'RE SO FOCUSED, I'VE GOT TO BE IN THE TRIAL BECAUSE IT OFFERS ME SOMETHING, HOPE THAT I REALLY NEED, AND MAYBE SOMETHING I REALLY BELIEVE IN, AND BUT, AGAIN, IT'S ALL OF THAT, SCREENING AND TESTS AND BLOOD WORK, BY THE TIME YOU'RE OUT YOU'RE THINKING WHAT WAS THAT ABOUT ANYWAY? I JUST WONDER IF THERE COULD BE A PRE-SOMETHING. A CONSENT ALONG THE WAY. ALSO I THINK COMPANIES OUGHT TO OFFER OR AT LEAST COULD THINK ABOUT OFFERING PSYCHOLOGICAL SUPPORT ALONG THE WAY. >> SOME STUDIES THAT WE GET FROM INVESTIGATORS DO DO THAT, RIGHT? THEY SHOW US THIS IS WHAT THEY WANT AND HAVE PEOPLE INTERESTED IN PARTICIPATING IN THE TRIAL, THERE ARE SOME TRIALS YOU WONDER WOULD A PATIENT CONSENT, HOW LONG WOULD IT TAKE? OFTEN BETTER APPLICATIONS DO HAVE THAT PROCESS BUT IT'S A WONDERFUL RICH DISCUSSION FOR US TO HAVE. THANK YOU. >> THANK YOU. SUE? >> BECAUSE WE'RE AMERICANS, WE ALMOST NEVER THINK ABOUT HUMAN RIGHTS. AND THERE ARE ENTIRE FRAMEWORKS OF HUMAN RIGHTS THAT HELP US THINK THROUGH THE RIGHTS OF THE CHILD, RIGHTS OF THE FAMILY, RIGHTS OF THE RESEARCHER. I WOULD SAY, PAT, YOU'VE DESCRIBED BEING UNDER DURESS IN THAT MEDICAL ENVIRONMENT WHERE EVERYTHING'S COMING AT YOU AND YET WE LET YOU SIGN SOMETHING AND SAY, YES, THIS IS OKAY. I THINK WHEN YOU'RE IN THE ICU, YOU'RE UNDER DURESS, IF YOUR MOTHER IS DYING IN FRONT OF YOU. BUT HOPE IS NOT AN EXCUSE FOR TORTURE. HOPE IS NOT AN EXCUSE FOR UNNECESSARY OR PAINFUL OR NON-PRODUCTIVE, QUOTE, INTERVENTIONS ON A PERSON. SO I THINK WE SHOULD THINK ABOUT THIS, WE SHOULD TAKE SOME STEPS BACK AS AMERICANS AND LOOK AT THE HUMAN RIGHTS COMMUNITY AND LOOK AT WORK THAT HAS BEEN DONE AROUND HUMAN RIGHTS. I THINK IF WE DID SOME WORK SERIOUSLY HERE, IT MIGHT EVEN HAVE BENEFITS TO THE ICU COMMUNITY AND TO OTHER PARTS OF MEDICAL PRACTICE, WHERE WE REALLY ARE UP AGAINST THIS VERY SERIOUS QUESTION. I PARTICIPATED IN A W .H.O.-SPONSORED FORUM IN MONTREAL AND WE WROTE SOMETHING CALLED THE MONTREAL DECLARATION ON INTELLECTUAL DISABILITIES, BUT THE DURESS YOU DESCRIBE IN MY EXPERIENCE IS SIMILAR TO WHAT SOME PEOPLE WITH INTELLECTUAL DISABILITIES GO THROUGH FOR THEIR LIFETIME WHERE THEY NEED A LOT OF SUPPORT TO UNDERSTAND THEIR RIGHTS, THEY NEED A LOT OF SUPPORT TO UNDERSTAND THE DECISIONS THAT ARE IN FRONT OF THEM. AND THIS STATEMENT WAS CREATED TO TRY TO FIGURE OUT WHAT ARE THE HUMAN RIGHTS THAT UNDERPIN THAT. I THINK THIS IS REALLY IMPORTANT. >> I AGREE. >> AND I KNOW DOCTORS THINK ABOUT HUMAN RIGHTS ALL THE TIME, BUT HOW MANY PEOPLE AS PART OF THEIR TRAINING PROGRAM TEACH THE UNIVERSAL DECLARATION OF HUMAN RIGHTS, WHICH WHEN WE SIGNED IT 50-SOME YEARS AGO PROMISED WE WOULD TEACH EVERYWHERE AND ALWAYS. THERE ARE SERIOUS QUESTIONS UNDERLYING THIS, SO THANK YOU. >> THANK YOU. TWO OTHER COMMENTS OR QUESTIONS AND WE'RE GOING TO GO TO OUR LAST SPEAKER IN THIS FORUM. NO, NO, A COMMENT. COMMENTS ARE WELCOME AS WELL. ESPECIALLY WHEN THEY COME WITH PASSION. BRIAN. >> EVERY OPPORTUNITY I HAVE TO SPEAK TO A FAMILY ABOUT PARTICIPATION IN CLINICAL TRIALS, I TELL THEM BEFORE THEY GO THROUGH THE SELECTION PROCESS OF WHAT MAGIC THEY HOPE TO PUT THEIR CHILD THROUGH, TO LOOK AT THE BURDEN OF PARTICIPATION. I'M NOT TRIVIALIZING WHAT CAN HAPPEN IN A CLINICAL TRIAL BUT I THINK THE BURDEN OF PARTICIPATION OFTEN CAN BE EXTRAORDINARY. I SPENT THE FIRST SEVEN MONTHS OF THIS YEAR TRAVELING BALTIMORE WITH MY 22-YEAR-OLD SON WHO OUTWEIGHS ME BY 40 POUNDS, IN A WHEELCHAIR, HE'S A SENIOR IN COLLEGE, WAS A JUNIOR AT THAT TIME. THERE ARE EXCEPTIONAL CHALLENGES TO THE FAMILIES. IREXPLAINED TO THEM FROM MY PERSPECTIVE DO YOU HAVE THE ABILITY TO PUT THAT MUCH ON A CREDIT CARD, HOW IT'S GOING TO IMPACT YOUR FINANCES, YOU WANT TO BUY A CAR OR HOUSE AND YOU'RE NOW TOP HEAVY, WHAT DOES IT DO FOR A CHILD'S SCHEDULE, WHETHER THEY ARE IN ELEMENTARY SCHOOL OR IN COLLEGE, WHAT'S IT GOING TO DO FOR YOUR ABILITY TO TRAVEL BASED ON YOUR WORK, AND ALL THESE OTHER CAVEATS THAT REALLY MAKE IT VERY BURDENSOME, AND THEN IF YOU BELIEVE THAT YOU CAN GET TO THAT POINT, AND YOU CAN HANDLE ALL THAT, THEN START LAYING THE CARDS DOWN AND SEE WHERE YOU WANT TO GO. >> I'M WONDERING IF THERE'S A NEED FOR A NEW TYPE OF PERSON IN THIS FIELD. SO ON THE DIAGNOSTIC SIDE YOU HAVE THE PHYSICIAN, YOU HAVE THE TESTING LAB, BUT A VERY IMPORTANT PERSON IS THE GENETIC COUNSELOR THAT HELPS THE FAMILIES MAKE THE RIGHT DECISIONS. ON THE THERAPEUTIC SIDE MAYBE WE NEED LIKE A THERAPEUTIC COUNSELOR, GENETIC COUNSELORS ARE DOING THIS IN THE CANCER FIELD, A LOT OF GENETICS IS USED TO DIAGNOSE, YOU THINK YOU HAVE A CANCER IN YOUR LIVER BUT IT REALLY WOULD RESPOND TO A DRUG THAT WOULD TREAT KIDNEY CANCER AND THE COUNSELORS ARE FORCED BECAUSE THE PATIENTS HAVE TO GET CONSENTED FOR GENETIC TESTING BUT THEY ARE HELPING WITH THE DIAGNOSTIC, WITH THE THERAPEUTIC ASPECT. IT SEEMS LIKE YOU NEED A PERSON THAT HAS TIME. GENETIC COUNSELORS SEE FIVE PATIENTS A DAY INSTEAD OF SEEING A PATIENT EVERY TEN MINUTES, SO THEY HAVE MORE TIME TO SPEND WITH THE FAMILIES AND MAYBE IF THERE WAS A GENETIC/THERAPEUTIC COUNSELOR THEY COULD HAPPY THE FAMILIES. >> PSYCHOLOGICAL SUPPORT, WHAT HAPPENS IS WHEN SOMETHING DISASTROUS HAPPENS, OR WORRISOME HAPPENS, AMAZINGLY THE NEXT STEP IS FACEBOOK, RIGHT? I HAVE TO VENT AND SAY THIS. FOR GOOD OR FOR BAD, THIS IS THEIR ACCESS TO A COMMUNITY THAT CAN GIVE THEM SUPPORT. I'M NOT SURE THAT THAT IS THE BEST SUPPORT WITHIN A CLINICAL TRIAL FOR ALL SORTS OF REASONS. >> TO ADDRESS KEVIN'S POINT, THERE'S A DEARTH THAT KNOW WHAT THEY ARE DOING. THAT'S PROBLEMATIC. THERAPEUTIC COUNSELORS IS A FIELD THAT HASN'T BEEN OPEN. DAN PEREZ? >> I JUST WANT TO SAY THAT I RESONATE DEEPLY WITH EVERYTHING YOU SAID. I THINK OUTSIDE OF D.C. THERE ARE MANY CONDITIONS THAT REQUIRE DEPTH OF SACRIFICE, CAREGIVERS, PEOPLE WITH DISEASES (INDISCERNIBLE) TO WHAT YOU SAID AND WANTED TO REFLECT ON DR. CAMPBELL'S REMARK, MY WIFE HAD STAGE 4 CANCER AND WE WENT TO 200 DAYS IN A HOSPITAL, RADIATION, CHEMO, SURGERIES. REALLY ONE OF THE FIRST IS A TRAINED SOCIAL WORKER, THE DIAGNOSIS, YOU CONNECT WITH A SOCIAL WORKER, AND THAT PERSON SORT OF BECOMES A TOUCHSTONE THROUGHOUT THE WHOLE TREATMENT. AND I CAN REMEMBER SUE'S SOCIAL WORKER SAYING YOU DON'T HAVE TO LIKE THE TREATMENT, YOU JUST HAVE TO GET THROUGH IT. AND THINKING WHAT A RIDICULOUS THING TO HEAR, GOING THROUGH ALL THE INFORMED CONSENT AND PROCESSES AND NOW SEEING ALL THE SIDE EFFECTS YEARS LATER, CURED, WHEN YOU'RE SIGNING CONSENT FORMS YOU REALLY DON'T THINK ABOUT IMPLICATION OF THINGS THAT WILL HAPPEN LATER, YOU JUST WANT TO BE CURED. I JUST WANTED TO SAY I THINK THE SOCIAL WORKER IS SOMEBODY THAT MIGHT BE A VALUABLE CONSIDERATION IN ADDITION TO THE GENETIC COUNSELOR. >> THANK YOU. THANK YOU, DAN AND THANK YOU, PAT, AGAIN, FOR THE PRESENTATION. THE NEXT PRESENTER IS THE CHIEF OF OBSTETRICS AND PEDIATRIC PHARMACOLOGY AND THERAPEUTICS BRANCH OF THE NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT. ANN IS PRESENTING ON VARIOUS IMPORTANT CONSIDERATIONS OF DESIGN OF CLINICAL TRIALS INCLUDING SELECTION OF ENDPOINTS AND ALTERNATIVES TO PROCEDURE CONTROLS. THANK YOU, ANNE, FOR BEING HERE. >> I HAVE A PROPOSAL ABOUT KEVIN'S COMMENT ABOUT THE THERAPEUTIC COUNSELOR, A GOOD ROLE FOR CLINICAL PHARMACOLOGISTS OR PharmD., SOMETHING LIKE THAT. INTERESTING CONCEPT. OKAY, THANK YOU. I PROBABLY HAVE TOO MANY SLIDES, I'LL ZIP THROUGH A FAIR AMOUNT OF THESE. SO MY JOB IS TO TALK ABOUT CHALLENGES IN DESIGN AND PERFORMANCE IN PEDIATRIC CLINICAL TRIALS AND TO COMMENT ON THE NEED FOR VALIDATED BIOMARKERS AND PATIENT REPORTED OUTCOME MEASURES WHICH HAS BEEN MENTIONED PREVIOUSLY AS WELL. I'M HAVING NO LUCK WITH THIS. HOLD ON. NO, OKAY. OKAY. SO FIRST I WANTED TO TALK ABOUT JUST BRIEFLY WHAT GOOD CLINICAL PRACTICE IS, THIS IS EXACTLY WHAT WE'RE TALKING ABOUT. THE FAILURES IN DRUG DEVELOPMENT, FAILURES IN CLINICAL TRIALS, CAN IN A LOT OF WAY BE ATTRIBUTED TO FAILURE OF INCORPORATION OF GOOD CLINICAL PRACTICE. GOOD CLINICAL PRACTICE IS INTERNATIONAL ETHICAL AND SCIENTIFIC QUALITY STANDARD FOR DESIGNING, CONDUCTING, RECORDING AND REPORTING TRIALS THAT INVOLVE PARTICIPATION OF HUMAN SUBJECTS. AND SO THAT THE CLINICAL TRIAL DATA ARE CREDIBLE, SO THIS IS WHAT WE'VE BEEN TALKING ABOUT ALL DAY, HANDLING OF SPECIMENS, DESIGN OF THE TRIAL, THE WHOLE BALL OF WAX IS AN ABSENCE OR A LACK OF INCORPORATE OF WHAT SHOULD BE GOOD CLINICAL TRIAL PRACTICES. TO USE A REALLY SIMPLE EXAMPLE, THIS IS THE RELIABILITY OF HEIGHT MEASUREMENT. HERE THEY HAVE A 100-YARD, 100-CENTIMETER METAL ROD. THEY USE A STADIOMETER, GOING TO A RULER AND WALL CHART. THE STADIOMETER IS PRETTY CLOSE, PRETTY ACCURATE AND PRECISE, THE DOTS ARE CLOSE TO 100 AND CIRCLING AROUND 100, YOU CAN SEE HOW EVERYTHING SPANS OUT THROUGH THE WALL CHART. FOR EXAMPLE, IF YOU'RE DOING A TRIAL LOOKING AT CHANGES IN HEIGHT OR BODY MASS INDEX AND SO ON, IF YOU CAN'T GET THE HEIGHT RIGHT WHICH IS LIKE THE SIMPLEST THING YOU COULD POSSIBLY IMAGINE, YOU KNOW, HOW ARE YOU GOING TO MOVE TO DO A BIGGER CLINICAL TRIAL, THAT'S GOING TO DEPEND ON THIS MEASURE? THERE WAS AN INTERESTING ARTICLE IN THE "NEW YORK TIMES" A COUPLE MONTHS AGO ABOUT FLOSSING. FEELING GUILTY ABOUT FLOSSING, MAYBE THERE'S NO NEED, TALKING ABOUT THE FACT THAT NO ONE HAD DONE A GOOD RANDOMIZED CONTROL TRIAL OF FLOSSING, WHETHER IT REDUCED PLAQUE OR CAVITIES WHICH WAS SORT OF FUNNY. AND THEN THIS PAST SUNDAY, THE SUNDAY REVIEW, A COMMENTARY ON FLOSSING AND THE ART OF SCIENTIFIC INVESTIGATION AND THE FACT THAT SOMETIMES IT WAS INCREDIBLY DIFFICULT TO PROVE SOMETHING USING A RANDOMIZED CONTROL TRIAL, SOMETHING AN IRB WOULD APPROVE. AGAIN THE DIFFICULTY IS STUDIES ARE HARD TO IMPLEMENT, IT SHOULD BE FAIRLY OBVIOUS. SO I WANTED TO DIGRESS A BIT AND TALK ABOUT A PROJECT AT MY INSTITUTES, THE NIH HAS BEEN INVOLVED IN THE BEST PHARMACEUTICALS FOR CHILDREN ACT. THE PURPOSE TO IMPROVE PEDIATRIC LABELING. AND WHAT WAS HAPPENING IS THAT THE PHARMACEUTICAL INDUSTRY WAS GIVEN ANOTHER SIX MONTHS ON ITS EXCLUSIVITY PERIOD. SOME WRITTEN REQUESTS WERE DECLINED AND ALSO A FAIR NUMBER OF DRUGS THAT LACKED PEDIATRIC LABELING WITH NOT A PATENT AND SO THERE WAS NO REAL BENEFIT TO PHARMA TO HAVE THIS EXTRA SIX MONTHS ON ITS PATENT LIFE. WE ENDED UP GETTING SOME VERY DIFFICULT WRITTEN REQUESTS FROM FDA, AND SO I WANTED TO TALK BRIEFLY ABOUT THEM. FIRST OF ALL, OUR JOB IN ADDITION TO DOING THE CLINICAL TRIALS IS ALSO TO PRIORITIZE DRUGS LACKING LABELING. OUR CONSIDERATIONS FOR PRIORITIZING WERE THEY THERAPEUTIC GAPS, DRUGS NOT LABELED FOR THESE CONDITIONS, POTENTIAL HEALTH BENEFITS, ADEQUACY OF NECESSARY INFRASTRUCTURE AND THEN NEONATES IN 2012. WE HAVE A REQUESTED PUBLIC OUTREACH, YOU CAN SEE A FAIR NUMBER OF ADVOCACY GROUPS PARTICIPATED, IF YOUR ADVOCACY GROUPS HAVE INTEREST IN PARTICIPATING WE WOULD LOVE YOUR INPUT. PLEASE LET ME KNOW. WE HAVE RECEIVED SEVERAL PEDIATRIC LABELS FROM THE FDA SO WE WERE ABLE TO COMPLETE THESE TRIALS. THIS IS JUST SOME OF THEM. THESE ARE SOME MORE EXPECTED. AND WHAT WE ENDED UP LEARNING AT LEAST AFTER THE ORIGINAL TRIALS WAS THAT WHAT WE NEEDED WAS INFRASTRUCTURE TO PERFORM THESE TRIALS, AND SO WE LET A CONTRACT FOR A PEDIATRIC TRIALS NETWORK TO STUDY VARIOUS THERAPEUTIC AREAS. THE NETWORK WASN'T SPECIFICALLY FOR ONE THERAPEUTIC AREA BUT A VARIETY OF THERAPEUTIC AREAS. IN IT ORDER TO MANAGE CLINICAL SITES TO DESIGN PERFORM AND ANALYZE PHARMACOKINETIC STUDIES, IN OTHER WORDS THE TIME COURSE OF DRUG CONCENTRATIONS OVER TIME, THE PHARMACODYNAMIC EFFECT, EFFECT OF THOSE DRUG CONCENTRATIONS ON PATIENT PARAMETERS LIKE SEDATION, BREATHING, SAFETY AND EFFICACY, DEVELOP DRUG ASSAYS, NEED FOR PEDIATRIC FORMULATIONS AND ONGOING PROBLEMS, VALIDATE DEVICES, AND ALSO TO DEVELOP ON THE JOB TRAINING AND APPLICATION OF GOOD CLINICAL PRACTICE. AS MUCH AS WE TRAIN PEOPLE TO DO THINGS UNLESS YOU REALLY HAVE SOME HANDS-ON EXPERIENCE AND ACTUALLY DESIGNING AND PERFORMING A CLINICAL TRIAL, YEAH, CAN YOU PARROT BACK WHAT YOU'RE SUPPOSED TO BE DOING BUT YOU'RE NOT REALLY INCORPORATING IT INTO YOUR PRACTICE. SO I THINK THIS IS AN ONGOING ISSUE ABOUT TRAINING INVESTIGATORS ABOUT REALLY HOW TO DESIGN AND PERFORM A CLINICAL TRIAL IN A WAY THAT IS AUDITABLE BY THE FDA. OUR PEDIATRIC TRIALS NETWORK HAS A NICE WEBSITE, IN THE LOWER RIGHT-HAND CORNER YOU CAN SEE THE STUDIES THAT ARE ONGOING. WE HAVE ABOUT 100 SUBCONTRACTS TO VARIOUS ACADEMIC CENTERS, ALL ACADEMIC CENTERS, ALL OVER THE PLACE, WHICH HAS BEEN NICE TO INCORPORATE A BROAD SWATH OF THE ACADEMIC POPULATION AND KNOWING HOW TO PERFORM A CLINICAL TRIAL ACCORDING TO BCP, AND THIS INSTITUTE, NIAMS, HAS TO DO WITH A TRIAL OF TOPICAL TIMOLOL THROUGH THE PRIORITIZATION PROCESS, WE TALKED ABOUT THE PROTOCOL, ENDPOINTS, RECEIVED OTHER ENDPOINT IDEAS AND WAYS OF MEASURING USING SPECIFIC CAMERA TECHNOLOGY THAT COULD BE REPRODUCED USING A CENTRALIZED BLINDED CORE TO READ PHOTOGRAPHS, AND TRIAL IS NOW RECRUITING. THERE'S A WHOLE BLUSH OF PEDIATRIC TRIALS AGAIN IN VARIOUS THERAPEUTIC AREAS, AGAIN THIS IS AVAILABLE ON THE PTN WEBSITE. AND AGAIN THESE DELIVERABLES WERE MORE THAN JUST TO GET TRIALS OUT THE DOOR. THEY WERE TO REACH AS MANY ACADEMIC INSTITUTIONS AS POSSIBLE SO THEY WOULD KNOW HOW TO DO PEDIATRIC CLINICAL TRIALS. WE'VE INCORPORATED NOVEL TRIAL DESIGNS SUCH AS INCORPORATIONS OF DATA BASE DATA BECAUSE AT THE END OF THE DAY IT GETS BACK TO THE FLOSSING EXAMPLE IS THAT THERE'S CERTAIN THINGS YOU'RE NEVER GOING TO BE ABLE, AT LEAST ON A LIMITED BUDGET, TO DO A RANDOMIZED CLINICAL CONTROL TRIAL OF. TO HAVE DATA, ON NORMAL VALUES, IS VERY USEFUL TO BOLSTER THE DATA YOU'RE ACTUALLY GETTING OUT OF THE RANDOMIZED TRIAL. ANOTHER POINT THAT THE NIH HAS BEEN VERY INTERESTED IN IS DATA SHARING. WE DO TRIALS. THESE DATA ARE PAID FOR WITH PUBLIC MONEY. THE DATA IS PUBLICLY AVAILABLE IN THREE WAYS. NUMBER ONE, PART OF THE BPCA PROCESS, THE DATA IS UPLOADED TO THE FDA DOCKET. IF YOU GOOGLE ANY OF THOSE DRUG PRODUCTS, YOU'RE WELCOME TO THE SLIDES AFTERWARDS, YOU CAN SEE THE DATA THAT'S ON THE FDA DOCKETED, IN PDF FORMAT BECAUSE THAT'S THE FORMAT THE FDA DOCKET SEMS, BUT THE DATA IS THERE, ARE THERE, DISCUSS ME. THE DATA CAN BE REQUESTED FROM PEDIATRICTRIALS.ORG AS WELL AS DATA AND SPECIMEN HUB NICHD PUT UP. AGAIN THEY HAVE UPLOADED A LARGE AMOUNT, THERE'S MORE COMING OF TRIALS THAT HAVE BEEN PAID FOR BY NICHD AND BY NIH. SO IF YOU'RE INTERESTED IN ACTUALLY LOOKING AT RAW DATA, IT'S AVAILABLE THERE. GETTING INVOLVED, OKAY. SO CHALLENGES IN PEDIATRIC TRIAL DESIGN AND PERFORMANCE, PROBLEM ONE, YOU NEED DESIGNS SPECIFICALLY FOR SMALL POPULATIONS. AND A LOT OF THIS ORIGINAL THOUGHT PROCESS WAS STARTED BY NASA. YOU HAVE ASTRONAUTS GOING IN SPACE, WHAT BECAME OBVIOUS WAS IT SEEMED THEY WERE WEAKER WHEN THEY CAME BACK DOWN. YOU'VE GOT THREE PEOPLE GOING UP THERE AT A TIME SO WE'RE NOT TALKING RANDOMIZED CLINICAL TRIAL OF 10,000 ADULT PATIENTS FOR HYPERTENSION, THREE PEOPLE IN OUTER SPACE FOR A VARIOUS AMOUNTS OF TIME. A LOT OF SMALL TRIAL DESIGNS WERE ORIGINATED BY NASA. AND SKIP MENTIONED SOME VARIOUS TRIAL DESIGNS AND ONE DESIGNS, THAT KIND OF THING. AGAIN, YOU CAN'T -- IT'S DIFFICULT TO ENVISION DOING AN RCT OF EVERY LAST THING SO THERE IS A REAL UTILITY FOR USE OF OBSERVATIONAL NATURAL HISTORY STUDIES INDICATED, WE MENTIONED THIS EARLIER THIS MORNING. THE THING THAT'S IMPORTANT THESE DATA HAVE GOT, AGAIN, GOT TO BE COLLECTED IN A VERY ORGANIZED WAY WHERE CAN YOU COMPARE DATA COLLECTIONS ACROSS SITES, ACROSS PATIENT TIMES, SO FOR EXAMPLE IF YOU'RE LOOKING AT, AGAIN, GETTING BACK TO THAT HEIGHT MEASUREMENT, IF YOU MEASURE THE HEIGHT ON A STADIOMETER ON TRIAL DATE NUMBER 1 AND TRIAL DATE NUMBER 365 THE CHILD IS SHORTER THAN HE WAS, YOU KNOW, A YEAR AGO, SOMETHING'S WRONG WITH THE MEASUREMENT SO, AGAIN, IT GETS BACK TO THE DATA COLLECTIONS HAVE GOT TO BE BULLETPROOF. THEY'VE GOT TO BE CORRECT. THEY HAVE TO BE ACCURATE AND THEY'VE GOT TO BE PRECISE. THE FDA HAS TALKED ABOUT EXTRAPOLATION WHERE POSSIBLE, SO THERE'S SITUATIONS WHERE THE FDA WILL EXTRAPOLATE EFFICACY FROM ADULTS TO PEDIATRIC POPULATIONS. I DO NOT BELIEVE DUCHENNE MUSCULAR DYSTROPHY WILL FIT INTO THIS BUT THERE'S SITUATIONS, FOR EXAMPLE, INFECTIOUS DISEASE WHERE THERE'S AN ASSUMPTION THE DISEASE PROCESS IN ADULTS, IN INFECTIOUS DISEASE IS SIMILAR, DISEASE COURSE SIMILAR IN A CHILD AS WELL SO DATA NEEDED IS NOT EFFICACY ANYMORE, IT'S SAFETY AND DOSING. THIS IS VERY HELPFUL TO USE EXTRAPOLATION IN SOME SORTS OF TRIAL DESIGNS. AGAIN, THE INCORPORATION OF DATABASE DATA, THE SAME SITUATION. IF YOU HAVE A DATABASE OR ELECTRONIC MEDICAL RECORD OF SOME KIND, THAT IS COLLECTING DATA IN SOME ACCURATE AND PRECISE WAY WHERE YOU CAN INCORPORATE THAT TO AUGMENT EITHER DATA USAGE INFORMATION, NORMAL VALUES AND SO ON, THIS IS VERY HELPFUL BUT AGAIN IT'S GOT TO BE IN A WAY THAT IS ALIGNED WITH GOOD CLINICAL PRACTICE. I WILL SAY THAT WE USED DATABASE DATA FOR THE MARAPENUM TRIAL. IT WAS QUITE HELPFUL. MARAPENUM IS A BROAD SPECTRUM ANTIBIOTIC FOR COMPLICATED INTRAABDOMINAL INFECTION, LACKING LABELING FOR VERY YOUNG INFANTS AND PREMATURE NEONATES. ONE QUESTION, IN COMPARISON WITH INAPEMUN, ANOTHER DRUG IN THAT CLASS, INAPEMUN CAUSED AN INCREASE IN SEIZURE INCIDENCE. THE QUESTION WAS DID MARAPENUM DO THE SAME THING BUT THE BACKGROUND QUESTION, BACKGROUND RATE OF SEIZURE IN BABIES IN THE NEONATAL INTENSEIVE CARE UNIT. WE INCORPORATED DATA FROM THE PEDIATRICS DATABASE WHICH INCORPORATES DATA FROM A HUGE NUMBER OF NEONATAL INTENSIVE CARE UNITS IN THE UNITED STATES IN ORDER TO AUGMENT THAT INFORMATION TO SHOW THE FDA THAT THE RATE IN THE MARAPENUM WAS THE SAME AS THE BACKGROUND RATE. THERE NEEDS TO BE AN INCORPORATION OF BIOMARKERS TO MINIMIZE INVASIVE TESTING. THIS HAS BEEN SAID MANY TIMES THIS MORNING. THE INTERESTING THING ABOUT READING THE NDA REVIEW OF THE NEWLY APPROVED DRUG WAS ABOUT FLAWS IN THE COLLECTION OF THE SIX MINUTE -- PERFORMANCE AND COLLECTION OF SIX-MINUTE WALK TEST DATA AND RUN. IT SEEMED THAT DEPENDING ON THE CLINIC, DEPENDING ON THE SITE, THE INVESTIGATOR, 6-MINUTE WALK COULD BE GRADED AT ZERO MEANING THE CHILD WAS NOT ABLE TO WALKS FOR 6 MINUTES OR THE TIME OR DISTANCE WAS RECORDED, IT MAKES THE COLLECTION OF DATA AND INCORPORATION OF DATA INTO A SINGLE DATABASE DIFFICULT TO ANALYZE. THE THING WITH THE 10-MINUTE WALK/RUN TEST, IF THE CHILD WAS UNABLE TO WALK OR RUN FOR FULL 10 MINUTES WAS THAT GRADED AS ZERO OR WAS THERE INTERMEDIATE TIME PERIOD WHERE IT WAS RECORDED THE CHILD WAS ABLE TO WALK OR RUN FOR 10 MINUTES OR SUCH A DISTANCE. THE OTHER THING THERE SEEMED TO BE DIFFERENT DIRECTIONS DEPENDING ON WHO THE PHYSICIAN WAS, DIRECTING THE CHILD, WAS THE CHILD ONLY SUPPOSED TO WALK, AS FAST AS HE OR SHE COULD, TO RUN AND SO ON. THERE WERE DISCREPANCIES WITH DATA. THIS HAS GOT TO BE STANDARDIZED, GETTING BACK TO THE GCP PROBLEM. THERE'S A DESPERATE NEED FOR OTHER BIOMARKERS HERE. IT'S SORT OF LIKE, YOU KNOW, WELL WE'VE TALKED ABOUT THIS BEFORE, AN EFFORT FOR BETTER BIOMARKERS. NEONATES ARE NOT WALKING OR RUNNING, THE 6-MINUTE TEST IS THE CLINICAL STANDARD, WITHOUT THE 6-MINUTE TEST, WE'RE DOING BASIC PROCEDURES, PUTTING CATHETERS IN THE HEARTS OF THESE NEONATES. IN ORDER TO MAKE SURE THAT THERE'S NOT UNDUE INFLUENCE IN KNOWING WHAT ARM THE CHILD IS RECEIVING TREATMENT FOR, ANY KINDS OF READINGS WITH THE TEST OR THE TISSUE SAMPLES NEED TO BE BLINDED SO THERE NEEDS TO BE A BLINDED READING CORE FOR THE CHANGE IN HEMANGIO SIZE. ANOTHER PROBLEM IS THE ISSUE MUCH NEED FOR VALIDATED GCP COMPLIANCE ASSAYS. THE SAMPLES HAVE AVAILABLE, IN CASE OF MUSCLE BIOPSY, BLOOD SAMPLES FROM NEONATES THAT WEIGH 500 GRAMS, PRECIOUS SAMPLES, THEY HAVE TO BE HANDLED THAT WAY, VALIDATED, RECORD OF HOW SPECIMENS ARE STORED, THAWs, FROZEN, DATA HAS TO BE HELD ON FOR SIGNIFICANT PERIOD OF TIME IF SOMEBODY DOES WANT TO COME BACK AND TAKE A LOOK AT DATA IT'S THERE AND DONE ACCURATELY AND CORRECTLY. AGAIN, THE NEED FOR DATA SHARING, AGAIN THE POINT IS THAT WITH THE TRIALS THERE NEEDS TO BE EXPECTATION OF FDA AUDIT SO THINGS HAVE GOT TO BE DONE ACCURATELY AND PRECISELY ACCORDING TO GCP FROM START TO FINISH HERE. I WANTED TO TALK ABOUT SOME NIH FUNDING OPPORTUNITY ANNOUNCEMENTS. MELISSA'S BRANCH HAS TWO OUTCOME MEASURE FOAs, FOR PRE-CLINICAL PRE-SEARCH ON MODEL ORGANISMS TO PREDICT TREATMENT OUTCOMES FOR DISORDERS ASSOCIATED WITH INTELLECTUAL AND DEVELOPMENTAL DISABILITIES, AND ONE FOR OUTCOME MEASURES FOR USE IN TREATMENT TRIALS OF INDIVIDUALS WITH INTELLECTUAL AND DEVELOPMENTAL DISABILITIES. SO IF YOU OR ANY ACADEMIC PEOPLE YOU KNOW HAVE AN INTEREST IN APPLYING FOR THESE FUNDING OPPORTUNITIES ANNOUNCEMENTS WE WOULD BE HAPPY TO RECEIVE THEM. WE HAVE A BIOMARKERS PAR OUT BRIDGING PEDIATRIC AND ADULT THERAPEUTICS, AND ONE ON FORMULATIONS AS WELL SO I WANTED TO LET YOU KNOW THOSE ARE AVAILABLE. A COUPLE OTHER ANCILLARY THINGS, WE DEVELOPED A NICE WORKING RELATIONSHIP WITH THE FOOD AND DRUG ADMINISTRATION. THIS ISSUE OF FORMULATIONS HAS BEEN ONGOING PROBLEM. WE PUT TOGETHER AN INTERAGENCY AGREEMENT WITH THE FDA SEVERAL YEARS AGO, AND THIS INFORMATION IS AVAILABLE ON THE NIH WEBSITE. THE PATIENT REPORTED OUTCOMES HAS ALSO BEEN MENTIONED THIS MORNING. NIH HAS A LARGE INITIATIVE ON THIS ISSUE OF DEVELOPING IMPORTANT OUTCOMES, THERE'S ONE SPECIFICALLY FOR CHILDREN. SO THESE ARE AVAILABLE, THE NIH IS HUGELY INTERESTED IN THIS ACTIVITY. ONE LAST THING IS THAT THE NIH HAS DEVELOPED AN ECHO PROGRAM, ENVIRONMENTAL INFLUENCES ON CHILD HEALTH OUTCOMES, WHICH IS LEVERAGING EXISTING COHORTS TO INVESTIGATE LONGITUDINAL IMPACT OF ENVIRONMENTAL EXPOSURES ON PEDIATRIC HEALTH. AND ADJACENT INITIATIVE, THE IDeA PROGRAM, INSTITUTIONAL AWARDS, SUPPORTING FACULTY DEVELOPMENT, RESEARCH INFRASTRUCTURE IN 23 STATES AND PUERTO RICO. STATES IN BLUE TEND TO RECEIVE OR NOT TEND TO RECEIVE, DO RECEIVE LESSER AMOUNTS OF NIH FUNDING THAN OTHER STATES. AND THE NICE THING ABOUT THIS IS THAT MONEY HAS BEEN SET ASIDE TO ENABLE NETWORKS TO RECRUIT PATIENTS FROM THESE SITES AS WELL, SO IT GIVES PATIENTS IN THESE LESS NIH-FUNDED AREAS THE ABILITY TO ENROLL IN CLINICAL TRIALS. AND THIS IS MY CONTACT INFORMATION. AND I'M DONE. THANK YOU VERY MUCH. >> THANK YOU VERY MUCH. [APPLAUSE] THE FLOOR IS OPEN FOR QUESTIONS OR COMMENTS. I HAVE ONE. SOMEHOW RECENTLY I'VE READ ABOUT -- YOU KNOW, AS YOU STATE, NIH HAS BEEN LONG INTERESTED IN DATA SHARING. >> UH-HUH. >> RECENTLY I READ, I CAN'T TELL YOU EXACTLY WHERE IT WAS, AN ANALYSIS OF HOW MUCH THAT DATA IS BEING UTILIZED. YOU PROBABLY KNOW BETTER THAN I DO, SO UNDERUTILIZED, 99.9% OF DATA OUT THERE IS NOT BEING TOUCHED. COULD YOU EXPAND AND TELL ME WHERE I READ IT? >> I DON'T KNOW WHERE YOU READ IT. WHEN YOU SAY UNDERUTILIZED, SOME PROBLEM IS WE TALK ABOUT DATA SHARING, AND IT SOUNDS FINE. I GUESS THERE ARE TWO POINTS. >> DATA UTILIZATION I SHOULD SAY. >> PROBLEM NUMBER ONE, WHEN THE DATA IS AVAILABLE BY CONTRACT, SO NIH PAYS FOR A PROJECT BY CONTRACT, DATA IS OWNED BY THE GOVERNMENT. WE CAN, IN OTHER WORDS, GO UP ON THESE WEBSITES. WHEN IT'S BY GRANT, THE DATA IS ACTUALLY OWNED BY THE INVESTIGATOR. I MEAN, THE NIH HAS THE RIGHT TO USE IT BUT THE INVESTIGATOR ACTUALLY HAS THE DATA. SO SOME OF THE PROBLEM WHEN THE DATA IS SHARED IS THE QUESTION OF THE GRANULARITY OF THE DATA. AND SOME OF THE RIGOR AND REPRODUCIBILITY THE NIH IS TALKING ABOUT HAS TO DO WITH THIS. SO, YOU KNOW, HOW GRANULAR IS THE DATA? CAN YOU ACTUALLY USE THE DATA OR IS IT SOME SORT OF TABLE WHERE THE DATA IS LUMPED TOGETHER WHERE YOU REALLY CAN'T FIGURE OUT, YOU KNOW, WHETHER THE DATA IS APPLICABLE OR NOT SO I DON'T KNOW. SO UNDERUTILIZED, THE NIH IS SPENDING X DOLLARS ON. >> WE WOULD LIKE -- BASICALLY WE WOULD LOVE FOR SOME DATA, WE FOUGHT FOR A LONG TIME, FOR EXAMPLE, THE FDA -- THE COMPANIES THAT HAD THE DATA ON THE NON-TREATED GROUP WHICH IS EXTRAORDINARILY VALUABLE. >> YES. >> DATABASE. >> YES. >> FOR NATURAL HISTORY STUDIES. >> UH-HUH. >> AS I UNDERSTAND IT, IT'S NOT BEING USED. IS THAT CORRECT? SKIP? >> I DON'T KNOW ABOUT THE NIH DATA. I HAD AN OPPORTUNITY TO HAVE A DISCUSSION WITH THE CRITICAL PATH FOLKS ABOUT THE PROJECT GOING ON. MY UNDERSTANDING FROM THEM IS THAT THEY ARE GETTING DATA SHARING OF THE CLINICAL TRIAL DATA FROM THE VARIOUS TRIALS BEING CONDUCTED FOR EXAMPLE IN DUCHENNE MUSCULAR DYSTROPHY, THEIR COMMENT WAS THEY ARE HAVING MORE OF A STRUGGLE GETTING THE DATA FROM ACADEMIC INVESTIGATORS THAN THEY ARE FROM INDUSTRY. >> BUT I DON'T DOUBT THAT ONE BIT. THE QUESTION IS UTILIZATION. >> WELL, IT'S BEING USED FOR THIS PROGRESSION DISEASE MODEL WHICH IS HOW THEY ARE DESCRIBING IT TO THE EXTENT TO WHICH THAT CAN PROVIDE, IF YOU WILL, A SORT OF BACKBONE FOR CLINICAL TRIAL DEVELOPMENT BUT I THINK THE TIME LINE FOR THAT IS PROBABLY A COUPLE OF YEARS. THERE MAY BE OTHERS AROUND THE TABLE ACTUALLY INVOLVED IN THE PROJECT AND CAN SPEAK FIRST HAND INSTEAD OF SECONDHAND >> KATHY? AND THEN SHARON. >> THANKS. YES, FOR A NUMBER OF YEARS IF YOUR PROJECT FOR NIH IS OVER A CERTAIN AMOUNT OF MONEY IT IS REQUIRED THAT THAT DATA IS MADE PUBLICLY ACCESSIBLE. THE DIFFICULTY IS IN THE IMPLEMENTATION OF THAT, HOW IT IS FOR PEOPLE TO GET ACCESS TO THAT DATA. SO EVEN THOUGH IT MAY BE PUBLICLY ACCESSIBLE IT MAY NOT BE SOMEONE KNOWS WHERE TO GO TO FIND THE DATA OR WHAT THE DATA LOOKS LIKE OR HOW IT'S CATEGORIZED. THERE'S A LOT OF DATA BUT PEOPLE DON'T HAVE THE ACCESS TO IT AND PEOPLE DON'T KNOWSLY HAVE THE ABILITY OR TOOLS TO UTILIZE THAT DATA BECAUSE IT'S NOT IN A FORMAT THEY CAN USE. WE'VE BEEN WORKING VERY HARD ON THAT. NICHD WAS CALLED TO THE TABLE LAST YEAR ASKING, YOU KNOW, IS YOUR DATA PUBLICLY ACCESSIBLE, AND WENT BACK AND LOOKED OVER THE LAST DECADE OR SO TO SAY OF THE DATA SETS THAT SHOULD HAVE BEEN PUBLICLY ACCESSIBLE HOW MANY WERE, WE COULD NOT GET INTO THE QUESTION OF HOW MANY ARE USED BUT HOW MANY COULD YOU ACTUALLY GET. WE HAD BETWEEN 70 AND 90% THAT YOU COULD FIND AND COULD GET. BUT THAT'S WHY WE LAUNCHED THIS WEBSITE, DASH, THAT ANNE MENTIONED, ONE PLACE, WELL CURATED, WELL CHARACTERIZED, YOU CAN GO THROUGH AND FIND WHAT TYPE MUCH DATA YOU MIGHT BE INTERESTED IN AND PULL THAT DOWN ASSUMING YOU MEET THE CRITERIA TO PULL THAT DOWN. I THINK THE IDEA OF HAVING DATA ACCESSIBLE, MAKING CERTAIN IT IS USABLE AND ENCOURAGING PEOPLE TO USE IT ARE INCREDIBLY IMPORTANT. >> SHARON? THANK YOU. >> SO I WAS GOING TO FOLLOW UP ON DATA UTILIZATION QUESTION, A CRITICAL PATH INSTITUTE, THEY BREAK DATA DOWN INTO SMALLEST MOST GRANULAR COMPONENTS AND DIG TO PUT IT ALL IN STANDARD FORMAT. I MEAN, THEY ARE PUTTING MOST OF THE DATA FOR PROGRAMS IN FORMAT BECAUSE A LOT WILL BE USED AND SUBMITTED TO FDA BUT THAT'S THE PLACE ANY CAN INVEST IN WORKING WITH CPAP OR A GROUP TO GET DATA INTO STANDARDS THAT ARE COMPATIBLE. IT'S TIME CONSUMING AND EXPENSIVE BUT HAVING DATA AVAILABLE IS JUST THE FIRST STEP. GETTING IT IN A COMPATIBLE FORMAT IS PROBABLY SOMETHING THAT HAS TO BE DONE ACTIVELY. >> SO WE HAVE STARTED A PROJECT ON DUCHENNE WITH CRITICAL PATH, AND SPENDING BASICALLY A MILLION DOLLARS ON THAT PROJECT. WE WOULD WELCOME -- WE'RE STRUGGLING TO GET ACADEMIC DATA. WE'RE GETTING INDUSTRY DATA. WE WELCOME ALL COLLABORATORS SO WE CAN DRIVE THAT PROGRESSION MODEL. >> THERE HAS BEEN A PUSH TO USE DATA STANDARDS. IT'S BEEN, I WOULD SAY, DIFFICULT TO GET THE ACADEMICS. THEY ARE CONCENTRATING ON RESEARCH, NOT DATA AT THE END OF THE DAY. SO, YOU KNOW, SOMETIMES WE GET THINGS IN EXCEL SPREADSHEETS, FOR EXAMPLE. I MEAN, NOT UNDER THIS PROGRAM BUT IN GENERAL, THE DATA TENDS TO NOT BE WELL CURATED, YEAH. >> WITH THE ACADEMICS ONE PLACE YOU MIGHT MAKE PROGRESS IS WORKING WITH THE JOURNALS BECAUSE THEY ALL WANT TO PUBLISH AND JOURNALS NOW ARE GETTING STRICTER ON WHAT THEY REQUIRE. FOR EXAMPLE, WESTERN BLOTS, YOU HAVE TO PUT THE FULL WESTERN BLOT IN A SUPPLEMENTARY MATERIAL. IN THE JOURNALS REQUIRED IT IN A CERTAIN FORMAT THEY WOULD RESPOND TO GET THEIR PAPERS PUBLISHES, THAT MIGHT BE THE WAY TO GO. >> ANOTHER ALTERNATIVE IS WHEN THE ANNOUNCEMENTS GO OUT FOR THE GRANTS IS TO MAKE SURE TO PUT IN THAT ANNOUNCEMENT HOW YOU WANT THAT DATA TO BE COLLECTED SO IT CAN BE STORED IN THAT MANNER. WE DO IN A IN SOME OF THE APPLICATIONS THAT COME THROUGH THE DIRECTED MEDICAL RESEARCH PROGRAMS, NOT SURE THAT'S ACCESSIONED AS MUCH AS COULD BE BUT COMING IN A COMMON FORMAT THAT MAY ALLOW CROSS STUDIES TO LOOK AT DATA IN AGGREGATE. >> THAT WAS REFERRING TO EXCESS THERE. YES, JIM? >> SO WE'VE HAD THIS ISSUE IN HEART LUNG AND BLOOD FOR A WHILE WITH HUGE CARDIOVASCULAR COHORTS FOR MANY YEARS. IT'S VARIABLE. FRAMINGHAM DATA IS ACCESS TO WHAT? PEOPLE LIKE TO USE THAT DATA, LONGITUDINAL, LOTS OF VARIABLES, NICE AND GOOD FOR MORE THAN JUST HEART DISEASE. >> RIGHT, USED FOR MANY, MANY THINGS. >> MANY THINGS. BUT THERE ARE OTHER CONDITIONS WHERE THIS MAY BE NOT QUITE AS ROBUST A DATABASE IS AVAILABLE BUT NOT USED OFTEN, AND WE FOUND THAT IN MANY WAYS, SOMEBODY MENTIONED IT AT THE END, YOU HAVE TO PAY PEOPLE TO USE IT KIND OF. WE'VE PUT OUT SEVERAL INITIATIVES THAT ARE RO3 SMALL GRANT PROGRAMS, VERY SMALL AMOUNT OF MONEY, $50,000, BUT, BOY, DANGLE THAT OUT THERE AND ALL OF A SUDDEN YOU OPEN THE FLOODGATES. I MEAN, MANY, MANY PEOPLE COME IN, WHETHER IT'S TO USE THE SAMPLES IN THE REPOSITORY WHICH WE HAVE THAT GO ALONG WITH THE DATA, BUT ALSO JUST TO USE SECONDARY ANALYSIS OF THE DATA. AND IT DOES WORK. IT'S UNFORTUNATE THAT WE HAVE TO DO IT THAT WAY BUT I THINK A LITTLE STIMULUS OFTENTIMES GOES A LONG WAY. YOU DON'T HAVE TO KEEP ON DOING THAT BUT A LITTLE PUSH GETS THE BALL ROLLING AND WE FOUND IT'S BEEN PRETTY GOOD IN TERMS OF GETTING SOME RETURN ON THAT DATA. >> AND JUST TO SUPPORT THAT, AGING INSTITUTE DOES AN ENORMOUS AMOUNT IN TERMS OF RO3s, SECONDARY ANALYSIS AND DATA, CMS, ET CETERA. >> JUST FROM THE ACCESS BOARD WHICH I CHAIR, THERE WOULD BE -- I WOULD HAVE TO MAKE A COMMENT DATA SHOULD BE ACCESSIBLE TO RESEARCHERS WOULD HAVE DISABILITIES. AND I THINK IT'S CLEAR WHY IT'S IMPORTANT TO INCLUDE THOSE RESEARCHERS IN THE TOPICS THAT WE'RE TALKING ABOUT TODAY. >> I DON'T THINK ANYBODY WOULD DISAGREE WITH THAT. OTHER POINTS OR QUESTIONS? >> DAN PEREZ, ON SHARING MATERIALS WITHIN THE CONTEXT OF WELL DONE CORES, JUST TO POINT OUT THAT THERE ARE DIFFERENT -- TEND TO BE DIFFERENT STANDARDS MATERIAL FOR ONE ACADEMIC LAB, AND ALSO SHARING WITH INDUSTRY. AND SO THE QUESTION IS, YOU KNOW, INDUSTRY, WE HAVE DIFFICULTY ACCESSING BIOMATERIALS DUE TO, YOU KNOW, INSTITUTIONAL (INDISCERNIBLE) OR OTHER CONSIDERATIONS, SO IT'S -- I JUST WONDERED WHETHER THAT'S SOMETHING THAT IS WRITTEN INTO THE WELLSTONE RFA, WHATEVER, IN TERMS OF SHARING OF MATERIALS OR WHETHER THAT'S THE LOCAL, WHETHER NIH HAS -- SO, A, WERE IT SHOULD BE REQUIRED AND MATERIALS SHARED WITH ACADEMIC AND INDUSTRIAL PARTIES, THAT KIND OF THING, OUT OF A CORE, YOU KNOW, OR A CELL CORE OR GENETIC TESTING CORE, THAT KIND OF THING. YOU KNOW, AND WHETHER OR NOT THAT STUDY IS BENEFICIAL OR NOT BENEFICIAL TO DO THAT KIND OF THING. I JUST WANTED TO RAISE THAT. >> YOU RAISE AN IMPORTANT POINT. AND THERE IS AN IMPORTANT DISTINCTION BETWEEN CONTRACTS AND GRANTS. THE -- ONE OF THE ISSUES HERE IS -- AND THOSE OF YOU THAT ARE INVESTIGATORS AROUND THE TABLE WOULD RELATE TO THIS, AND THAT IS PEOPLE THINK THAT THE ONLY TIME THEY WILL BE FINISHED REALLY LOOKING AT THEIR DATA IS WHEN THEY ARE DEAD. NO SOONER. SO THEY TRY TO KEEP THAT DATA TO THEMSELVES. BUT IN FACT, IF IT'S A CONTRACT, IF IT'S A CONTRACT, WE, THE NIH, HAVE CONTROL OVER THAT. SO WE HAVE HAD TREMENDOUS SUCCESS WITH BIG INITIATIVES LIKE THE ALZHEIMER'S DISEASE NEUROIMAGING, OSTEOARTHRITIS IMAGING WHERE WE'VE ACTUALLY CONTRACTED AND UTILIZATION OF MATERIAL IS UTILIZED UNDER THE CIRCUMSTANCES AND UNDER THE AGREEMENTS THAT WE PROVIDE. WHEN IT'S A GRANT, IT'S A DIFFERENT STORY. THE GRANT I THINK SOMEONE SAID EARLIER, THE GRANT REALLY BELONGS TO THE INSTITUTION. AND THE INSTITUTION HAS POLICIES. NOW, AS GLEN REMINDED ME, WE DO HAVE DATA SHARING. WE ASK THE REVIEWERS TO LOOK AT THE DATA SHARING COMMITMENT OF PEOPLE. BUT CAN THEY BE HELD TO IT? NOT NECESSARILY. YOU CAN'T NECESSARILY DO IT, IF YOU DON'T OWN THE MATERIAL. WE HAVE A WONDERFUL CASE IN POINT, I CAN'T REALLY TALK ABOUT IT SPECIFICALLY, A CASE IN POINT WHERE SOMEBODY CAME ALONG AND A COMPANY CAME ALONG, AND WANTED TO GET THE -- NOT THE DATA BUT SOME MATERIAL FROM BOTH THE NIH AND ALSO FROM INSTITUTIONS, AND IT WAS HARD TO RECONCILE THE BAR THAT WAS -- DIFFERENT BARS THAT WERE SET, BY DOLE COMES INTO THIS IN TERMS OF INTELLECTUAL PROPERTY, IF YOU'RE A COMPANY YOU WANT TO USE MATERIAL THAT'S BEEN COLLECTED BY AN ACADEMIC INVESTIGATOR. WELL, HOW MUCH OF -- YOU CAN'T FORCE THEM, UNLESS THERE'S SOME SORT OF A NATIONAL EMERGENCY. SO I THINK IT'S A VERY DIFFICULT POINT. AND THAT'S THE SUBTLETY THAT I KNOW OF. MAYBE, GLEN, DO YOU KNOW OF ANOTHER WAY AROUND THIS? >> YEAH, YOU KNOW, IT'S SOMETHING THAT COMES UP IN PEER REVIEW FROM TIME TO TIME, PARTICULARLY FOR RENEWAL APPLICATIONS, WHEN, YOU KNOW, WE LIKE TO SEE REVIEWERS CONSIDER, HAVE THEIR AWARDEES FOLLOW THROUGH ON PRIOR PLANS FOR SHARING. BUT, YOU KNOW, IT'S A HARD THING TO COLLECT SPECIFIC DATA AND WE'RE ASKING ESSENTIALLY THE INVESTIGATOR TO CONFIRM THEY HAVE DONE WHAT THEY SAID THAT THEY WOULD, SO ... >> I GUESS THE OTHER KIND OF INTERMEDIATE CASE, COOPERATIVE AGREEMENTS, WHERE OFTEN PART OF THE AGREEMENT IS THAT THERE WILL BE DATABASES SET UP AND MADE ACCESSIBLE, AND IF IT'S A CONSORTIUM OF INVESTIGATORS THEY WILL AGREE ON THE KINDS OF DATA THEY WILL ALL COLLECT SO THE CUMULATIVE DATA IS MORE USEFUL THAN JUST THAT FROM ANY INDIVIDUAL LAB. WE'RE GETTING A LOT OF THAT FOR THE BRAIN INITIATIVE, FOR EXAMPLE. >> BUT THE ACTUAL QUESTION THAT WAS RAISED WAS AVAILABILITY TO COMMERCIAL, AND THE OTHER ISSUE IS THE CONSENT. I MEAN, HOW HAS THE CONSENT BEEN WRITTEN? THAT IT CAN BE UTILIZED BY ACADEMIC INVESTIGATORS OR IS IT WIDE OPEN? NOW, SOME OF THE NEW CONSENTS ARE WRITTEN AS TO BEING WIDE OPEN. >> WELL, I THINK THIS IS WHERE THE PRIVATE FOUNDATIONS COULD ACTUALLY HELP. RIGHT NOW I WORK FOR THE HOWARD HUGHES MEDICAL INSTITUTE SO EVERYTHING I HAVE I DONATE, ALL THE MICE DONATED SINCE THEY PUBLISHED, THEIR RULES, NO MTAs, IT'S SIMPLE. IF I HAD TO DONATE AS PROFESSOR AS OF THE UNIVERSITY OF IOWA THERE'S A LOT OF PAPERWORK TO GIVE THINGS OUT. THE UNIVERSITY THINKS EVERYTHING HAS I.P. ASSOCIATED, IT'S GOING TO MAKE THEM MILLIONS OF DOLLARS. FOUNDATIONS LIKE FMA AND DAN MENTIONED HE JUST MADE A NEW MOUSE, DUX4 MOUSE, WHEN THEY DO THAT AND DONATE THEM AND THEY CAN ACTUALLY BE READILY AVAILABLE, IN THE PRIOR FOUNDATIONS MAKE REAGENTS LIKE MICE, ANTIBODIES, OTHER THINGS AND DONATE THEM TO THE JACKSON OR OTHER PLACES, IT MAKES IT MUCH EASIER FOR A LOT OF PEOPLE TO USE IT. THE UNIVERSITIES ARE OBSESSED NOW WITH I.P. AND IT'S SO DIFFICULT TO GET ANYTHING DONE SO EVEN WHEN SOMEONE WANTS TO GIVE YOU A REAGENT, YOU KNOW, THEY ARE HAVING A HARD TIME DOING THAT. >> KEVIN, THIS IS WHY WE'RE HAVING A MOUSE MADE AT JACKS, SO WE DON'T HAVE LICENSING REACH THROUGH -- I.P. REACH THROUGH. IN RARE DISEASES, PARTICULARLY BARRIERS, SMALL BIOTECH COMPANIES WANT TO ENGAGE. IF THEY ENCOUNTER MANY BARRIERS, YOU LOSE 'EM. >> THAT'S REALLY GOOD BECAUSE A LOT OF THE PEOPLE THAT ARE FUNDED FROM NIH TAKE THE NIH MONEY TO MAKE THE MOSS AT JACKS AND THEY OPEN IT, WHY NOT SKIM THAT PART AND HAVE THE MICE MADE DIRECTLY, THAT MAY BE SOMETHING NIH CAN DO, IF YOU MAKE A MOUSE OR REAGENT THAT ESSENTIALLY NIH DOES IT. THE MONEY IS THE SAME AMOUNT OF MONEY BUT NIH COULD PROBABLY GET IT CHEAPER AND HAVE JACKSON MAKE IT AND MAKE IT AVAILABLE. >> I HAVE GOTTEN COMPLAINTS AS INSTITUTE DIRECTOR PEOPLE ARE NOT SHARING. YOU SEE, IF IT'S MICE, IF IT'S A -- IF IT'S MICE, THEY ARE REQUIRED TO SHARE WITHIN A CERTAIN AMOUNT OF TIME. A LIMITED AMOUNT OF REAGENT ANTIBODIES, ALTHOUGH THEY CLAIM TO BE ABLE TO SHARE, THEY CAN SAY, WELL, THERE'S LIMITED NUMBER. >> (INAUDIBLE). >> WELL, IF IT'S AVAILABLE. IF IT'S AVAILABLE. YES, SKIP. >> I GUESS, YOU KNOW, AS AN OBSERVER AND FORMER ACADEMIC WITH SOME NIH GRANTS MY IMPRESSION IF YOU'RE DEALING IN THE TRANSLATIONAL SPACE GETTING INTO THE CLINIC, NOT GRANTS, SORRY, CONTRACTS WOULD BE MORE EFFECTIVE, WATCHING WHAT ANNE HAS DONE THROUGH BPCA, DIDN'T GO ANY WHERE UNTIL THEY SWITCHED TO CONTRACTING. GIVING THE INVESTIGATOR FREEDOM TO MOVE IN DIFFERENT DIRECTIONS THAT A GRANT MAY OR MAY NOT BE AS EFFECTIVE -- THAT A CONTRACT MAY OR MAY NOT BE AS EFFECTIVE BUT MY HYPOTHESIS IF YOU'RE LOOKING AT GETTING THINGS TO THE BEDSIDE THAT A CONTRACT IS THE WAY THAT YOU'RE GOING TO ACTUALLY GET PERFORMANCE. >> I AGREE WITH YOU COMPLETELY. BUT IT'S INVERSELY PROPORTIONAL TO THE DIFFICULTY OF GETTING CONTRACTS NOW THROUGH THE GOVERNMENT WITH REGARD TO RESTRICTIONS. OUR CONTRACTORS ACTUALLY ARE NHLBI AND THE CHANGE IN THE LAST 7 OR 8 YEARS HAS BEEN ABSOLUTELY ENORMOUS. SO THAT THERE ARE SOME TECHNICAL DIFFICULTIES IN REALLY RUNNING THOSE CONTRACTS. YOU MUST SEE THE SAME THING AT NINDS. SO MANY OF THE THINGS THAT WE USED TO DO BY CONTRACT, WE CAN'T DO BECAUSE IT TAKES TOO LONG, MAY TAKE A YEAR-AND-A-HALF OR TWO YEARS TO GET THE CONTRACT WRITTEN. SO I AGREE WITH YOU PHILOSOPHICALLY. ONE LAST QUESTION, ONE OF MY PET PEEVES, MANY YEARS, THIS BPCA. SO CHILDREN ARE REQUIRED TO BE INCLUDED IN STUDIES. MAYBE ANNE I'VE TALKED TO YOU ABOUT THIS, I DON'T KNOW WHETHER I'VE TALKED TO ANYBODY ABOUT THIS, BUT IT REQUIRES THE CHILDREN TO BE INCLUDED BUT DOESN'T REQUIRE ANY CALCULATION OF HOW MANY CHILDREN NEED TO BE USED IN ORDER TO ACTUALLY GET AN ANSWER, AND, SKIP, YOU CAN ANSWER THAT. >> THERE'S A BIG DIFFERENCE. WELL, WITH ALL DUE RESPECT, I'VE WRITTEN AND AT ONE POINT CRITICIZED NIH POLICY FOR THE INCLUSION OF CHILDREN PRECISELY AROUND THE FACT THEY WEREN'T INCLUDED, NECESSARILY TO THE LEVEL OF DRAWING A CONCLUSION ABOUT THAT POPULATION. BASICALLY, YOU KNOW, AN ASTHMA STUDY FOR EXAMPLE, OFTEN 12 AND UP BECAUSE WE DON'T THINK ASTHMA IS DIFFERENT IN A 15-YEAR-OLD THAN 25-YEAR-OLD SO WHAT YOU'RE BASICALLY DOING THERE IS EXTRAPOLATING EFFICACY YOU SEE FROM THE WHOLE POPULATION TO BOTH ADULTS OR ADOLESCENTS THAT MAY BE UNDERPOWERED BUT IF YOU NEED DATA ON CHILDREN SEPARATELY IT HAS TO BE POWERED TO ANSWER THAT QUESTION AND ANYTHING LESS IS UNETHICAL. >> THE BPCA DOES NOT REQUIRE THAT. >> THE ALLOWS THE FDA TO WRITE A WRITTEN RESPONSE, THIS IS WHAT WE WANT. IF WE ASKED FOR SOMETHING THAT WASN'T ADEQUATE WE SHOULD BE CRITICIZED SO I WOULD HAVE TO DEFER TO THOSE ANNE HAS RECEIVED. SAMPLE SIZE CALCULATIONS ARE PART OF THE WRITTEN REQUESTS. IT WOULD BE NICE IF THOSE WERE PUBLIC WHEN THEY ARE ISSUED BUT UNFORTUNATELY THEY ARE ONLY PUBLIC NOW WHEN EXCLUSIVITY IS GRANTED, WHICH IS AT THE END. >> A COMMENT? >> WHEN WE GO TO THE REVIEW DIVISIONS WE HAVE CONVERSATIONS ABOUT POWER CALCULATION, NO QUESTION. THERE'S A MEETING GOING ON THIS AFTERNOON AT 2:00 ABOUT THIS VERY ISSUE WITH FDA. SO WE DEFINITELY DO HAVE THOSE CONVERSATIONS. >> THANKS VERY MUCH. THANKS VERY MUCH TO EVERYONE, BOTH PRESENTERS AND THE DISCUSSANTS. I THINK THAT -- DID I CUT DAN OFF FOR A COMMENT? I DIDN'T MEAN TO. >> WE'RE FINE. THANK YOU. >> OKAY. SO AS WE'VE BEEN TALKING ABOUT MANY DIFFERENT BROAD SPECTRUM OF TOPICS WHEN IT COMES TO ETHICAL CONSIDERATIONS, GLEN HAS CAREFULLY NOTED SOME OF THE ISSUES THAT WE HAVE HERE. THE QUESTION AND CHALLENGE IS ARE THERE ANY ACTIONABLE ITEMS? >> THANKS, STEVE. WE'VE REALLY COVERED A LOT OF TERRITORY IN THIS SESSION ON ETHICAL DESIGN OF CLINICAL TRIALS. SOME THINGS I HEARD WERE SUGGESTIONS FOR STANDARD OPERATING PROCEDURES FOR BIOPSY HANDLING, ENCOURAGING IRBs TO BRING CASES TO THE FDA FOR OPEN DISCUSSION OF ETHICAL CONSIDERATIONS, GUIDANCE TO TRIAL PARTICIPANTS SO THEY UNDERSTAND ABOUT THERAPEUTIC MISCONCEPTION OR MISESTIMATION, PARTICIPANT BURDEN, PERHAPS CREATE A CONTROL FOR THERAPEUTIC COUNSELOR, NEED TO COLLECT DATA IN A TRIAL DESIGN, PSYCHOLOGICAL SUPPORT FOR TRIAL PARTICIPANTS AND FAMILIES, AND THEN THIS LAST PART OF THE DISCUSSION ON THE NEED FOR STRATEGIES TO ENCOURAGE MORE SHARING OF CLINICAL DATA AND OTHER RESEARCH RESOURCES. ARE THERE OTHER MAJOR SUGGESTIONS THAT CAME UP THAT YOU THINK WE SHOULD ADD TO THOSE? >> I WOULD JUST INCLUDE SOMETHING ABOUT MAKING SURE THAT EVERYTHING THAT'S DONE AROUND A CLINICAL TRIAL IS DONE ACCORDING TO GOOD CLINICAL PRACTICE SO THE DATA COLLECTIONS ARE DONE ACCORDING, YOU KNOW, STANDARDIZED, THE SAME THING WITH THE SAMPLE HANDLING THAT ASSAYS ARE STANDARDIZED, STANDARD OPERATING PROCEDURE AROUND THE WHOLE CLINICAL TRIAL SO THE DATA IS COMPLETELY INTERPRETABLE AND AUDIBLE. >> MEASURE AND BIOMARKERS THAT KEEP POPPING UP IN THE DISCUSSION. >> RIGHT. >> OUTCOME MEASURE, TIGHTLY INTEGRATED BIOMARKERS. >> YEAH, GOING BACK TO THE ISSUE OF TRUE INFORMED CONSENT I THINK A RECOMMENDATION COULD BE MADE TO THE INSTITUTION, THE IRBs SHOULD PROBABLY TAKE A LARGER ROLE IN ADVOCACY SHOULD NOT HAVE TO TAKE AS LARGE A REALLY IN TERMS OF BEING THE SUBJECT ADVOCATE. MANY IRB OFFICES HAVE A SUBJECT ADVOCATE, SITTING IN HOPEFULLY ON INFORMED CONSENT PROCESSES SO I THINK STRENGTHENING THAT ROLE WITHIN THE INSTITUTIONS IS WHERE THE BURDEN SHOULD LIE. >> OKAY. WITHIN THE INTRAMURAL PROGRAM THAT'S BEEN STANDARD PROCEDURE FOR MANY YEARS NOW, THAT PATIENT ADVOCATE RIGHT AT THE TABLE AT THE IRB. >> ALSO ON THE DSMV, THERE'S SITUATIONS WHERE THE GOALS OF THE INVESTIGATORS CAN BE CROSS OPINION PURPOSE TO THE GOALS OF THE PARTICIPATING PATIENTS. YOU KNOW, WE'VE GOT THAT CAPTURED AND WE'LL DEVELOP THE SUMMARY FROM THIS SESSION THAT, YOU KNOW, WE'LL SHARE WITH YOU AND WE'LL POST ON THE MDCC WEBSITE. IT HELPS US TO THINK ABOUT WHAT ARE POTENTIAL ACTION ITEMS THAT WE CAN DERIVE FROM THIS AND, YOU KNOW, IT WILL FUEL THE DEVELOPMENT OF AGENDAS FOR FUTURE MDCC MEETINGS. >> STEVE, ANYTHING ELSE? >> NO, NOT FOR THIS SESSION, BUT I WANT TO GET BACK TO OUR OPENING, AND THAT IS THAT AT THE MEETING IN APRIL WE TALKED ABOUT THE PATIENT ACCESS TO CLINICAL CARE SERVICES AND DURABLE MEDICAL EQUIPMENT. AT THAT MEETING WE DECIDED TO FORM A WORKING GROUP. DOCTORS WICK, DENGER AND NUCKOLLS, AND ANNIE KENNEDY IS PARTICIPATING. IF THERE ARE OTHERS I DON'T KNOW. >> PETER AND MICHAEL, DAN PEREZ, I THINK JOHN IS SITTING IN FOR MDF. >> SO THAT, THE MEMBERS OF THIS WORKING GROUP WILL MEET AT A BREAKOUT GROUP DURING OUR LUNCH BREAK, AND GLEN WILL PROVIDE GUIDANCE AS TO WHERE THOSE PEOPLE ARE GOING TO GO. AND THEN WE EXPECT AT 1:30 TO RECONVENE AND FOR THERE TO BE A SHORT REPORT OUT FROM THAT GROUP. >> GLEN, I'LL NEED TO CALL IN IN 10 OR 15 MINUTES, I'LL BE LATE CALLING YOU ON THE OTHER ONE. >> OKAY. >> THANK YOU. >> YEAH, SO THOSE OF YOU WHO ARE ON THE WORKING GROUP AND IT'S NOT TOO LATE TO JOIN THE WORKING GROUP, IF YOU'RE INTERESTED IN IT. WE'D REALLY LIKE TO HAVE MORE PARTICIPATION OF OUR MEMBER FEDERAL AGENCIES. SO WE'RE GOING TO BE MEETING UPSTAIRS IN 2172, IN THE CONFERENCE ROOM UP THERE. YOU CAN GRAB YOUR LUNCH AND HEAD UP THERE AND I'LL SHOW YOU WHERE THAT IS. >> WE'LL RECONVENE AT 1:30. WE THANK EVERYONE WHO IS ON THE SUBCOMMITTEE. I KNOW BRIAN AND VALERIE ARE GOING TO BE REPORTING OUT ABOUT AT LEAST SOME OF THE TOPICS THAT WE'RE -- WE HAVE DISCUSSED. AND THEN THE QUESTION IS, WHAT STRATEGIES FOR AFFECTING POSITIVE CHANGE CAN BE MADE WHERE DID SOME OF THOSE RESPONSIBILITIES LIE. BRIAN. >> THANK YOU. SO WE HAD QUITE A LIVELY DISCUSSION ABOUT WHAT THE CHARGE OF THE GROUP MIGHT BE, SOME OF THE AREAS THAT WE MAY CONSIDER ADDRESSING AND THEN ALSO THE PROCESS, HOW TO GO ABOUT BOTH IN SELECTING THOSE PARTICULAR AREAS THAT WE MIGHT HAVE SOME IMPACT IN AND WHAT INFORMATION, WHAT RESOURCES ARE NEEDED FOR US TO MAKE THAT. WE SPEND A LOT OF TIME DISCUSSING VARIOUS ASPECTS OF A CHARGE, WHICH WE'LL HELP THE GROUP IN GUIDING US AS TO WHERE WE FEEL WE'RE GOING TO BE ABLE TO MAKE AN IMPACT. AND I THINK THE MOST IMPORTANT PART OF THIS IS WE WISH TO ENGAGE BOTH OUR PUBLIC AND PRIVATE MEMBERS OF THE MDCC IN THE DEVELOPMENT OF THE STRATEGY. SO WE SEE THIS AS AN ONGOING PROCESS. AGAIN, THE DETERMINATION OF WHAT WE CAN DO, HOW WE CAN MAKE AN IMPACT, LOOKING FOR AREAS OR ISSUES THAT ARE EXTRAORDINARILY OVERWHELMING, A HUGE BURDEN ON TIME. AND ALSO AFFORD US A CERTAIN AMOUNT OF SUCCESS SO WE CAN MAKE SOME CHANGE. WE TALKED A LOT ABOUT FEDERAL PARTNERS AS WELL AS THE PRIVATE PARTNERS IN THIS ORGANIZATION, THIS COMMITTEE, WHO HAVE QUITE A BIT OF DATA AVAILABLE. ONCE WE IDENTIFY THROUGH A SERIES OF EMAIL OR MEETINGS, THE AREAS WE HOPE TO ADDRESS, THAT WILL HELP US IN THE SELECTION OF WHAT TYPE OF INFORMATION WE NEED TO SUPPORT THE EFFORT WE PLAN TO UNDERTAKE. >> TO THAT POINT WE TALK ABOUT ENGAGING OTHER ORGANIZATIONS WHO MIGHT NOT BE PART OF MDCC. WE KNOW THERE ARE DEFINITELY OTHER MUSCULAR DYSTROPHY GROUPS, WANT TO MAKE CERTAIN WE'RE AS INCLUSIVE AS POSSIBLE IN TRYING TO ADDRESS THESE ISSUES. >> WE DEVELOPED A SERIES OF STEPS WHICH WE HOPE TO UNDERTAKE IN BOTH SELECTION OF THE ACTIVITIES WE PLAN TO UNDERTAKE AS WELL AS STEPS ON THE IDENTIFICATION OF WHAT DATA WE MAY NEED TO MAKE THESE CHANGES. OR IMPROVEMENTS TO SOME OF THE SYSTEMS THAT ARE OUT THERE. THERE WAS A LOT OF DISCUSSION ABOUT SOME OF THE TOPICS ALREADY THAT THE -- SOME OF THE PARTICIPANT ARE INTERESTED IN. I THINK AT THIS POINT IT WOULD BEHOOVE US TO STEP BACK AND SAY LET'S COLLECT A GROUP OF THOSE IDEAS AND THEN ADS A GROUP FIND OUT -- FIGURE OUT WHAT INFORMATION WE NEED TO MAKE ANY CHANGES, IMPROVEMENTS IMPACT ON THE SITUATION THAT IS A PRIORITY. THAT WILL HELP US TO PLAN A STRATEGY TO ADDRESS THOSE PARTICULAR TOPICS. >> CERTAINLY DEVELOPING STRATEGIES ARE IMPORTANT BUT AS WE'RE THINKING ABOUT THOSE STRATEGIES AND WHAT THE IMPLEMENTATION PLAN MIGHT BE, TO ADDRESS THOSE STRATEGIES WE WANT TO MAKE CERTAIN WE HAVE WELL ESTABLISHED MILESTONES AND OUTCOMES TO MEASURE PROGRESS. TO SHOW THAT WE'RE HAVING AN IMPACT. THERE WERE A COUPLE OF POINTS MADE THAT WE REALLY NEED TO MAKE CERTAIN WE'RE SETTING CLEAR GOALS. WHAT ARE WE TRYING TO ACHIEVE? WE'RE IN THE JUST TRYING TO IDENTIFY BARRIERS. WHAT CAN WE IMPACT AS THIS COMMUNITY AND THE LARGER COMMUNITY AS WELL? >> TO THAT END WE HAVE DECIDED TO START WITH EVERY OTHER MONTH TELECONFERENCES AND IN BETWEEN WE WILL PROBABLY HAVE AN EXCHANGE OF EMAIL SO THAT WE CAN STAY ON TASK. WITH CLEAR AND DEFINED PRIORITIES WITHIN THAT PERIOD SO WE'RE STAYING TO OUR GOAL. SO I THINK THE FIRST AREA WE HOPE THE ADDRESS IS IDENTIFICATION OF LIST OF PRIORITIES FROM AMONG THE PARTICIPANTS OF WHERE THEY SEE THIS GROUP MAKING SOME IMPACT. FROM THERE WE WILL HOPEFULLY BE ABLE TO GLEAN SOME AREAS WE MIGHT BE ABLE TO GAIN ADDITIONAL INFORMATION AND REACH OUT TO SOME OF THE PARTNERS ON THIS -- THE COMMITTEE FOR ADDITIONAL INFORMATION AS NEEDED. >> SO I WOULD SUGGEST IN THINKING ABOUT THAT, YOU THINK ABOUT WHAT THE LOW HANGING FRUIT ARE. BECAUSE HAVING -- I DON'T KNOW WHETHER THERE ARE ANY LOW HANGING FRUIT IN TERMS OF ACCESS TO CARE BUT IF THERE ARE TO SORT OF ATTACK THAT TO SEE HOW THAT CAN BE ATTAINED AND WHERE THE RESPONSIBILITY WOULD LIE AND TALK TO YOUR POINT VALERIE IN TERMS OF MILESTONES MET, GOOD TO HAVE THAT UNDER YOUR BELT. SO I WOULD THINK ABOUT THAT AS YOU'RE LISTING THINGS, NOT NECESSARILY ONLY THE PIE IN THE SKY THOUGH GREAT TO SHOOT FOR THAT PIE IN THE SCOOT. -- SKY. >> THERE'S ALSO BEEN DISCUSSION ABOUT KIND OF THE SCOPE OF THE ISSUES WE TAKE ON, SOME OF THEM MAY BE MORE SPECIFIC TO THE MUSCULAR DYSTROPHIES AND AN EXAMPLE THAT I WOULD GIVE ARE PLANS TO ENCOURAGE REVISIONS OF THE ICD CODES TO INCLUDE MORE SPECIFIC MUSCULAR DYSTROPHIES AND OTHERS CROSS CUT RARE DISEASES OR CHRONIC DISEASES, MUCH BIGGER THAN THE MUSCULAR DYSTROPHIES LIKE ACCESS TO DURABLE MEDICAL EQUIPMENT AND I THINK IN EACH CASE WE'LL TRY TO LOOK AT WHAT WE'RE TRYING TO ACCOMPLISH AND DETERMINE ARE WE THE RIGHT GROUP TO BE WORKING ON THIS, DO WE NEED TO BE PARTNERING WITH OTHER GROUPS, LET'S NOT REINVENT THE WHEEL, HOW WE CAN ADD MOMENTUM AND OF COURSE PLACES WE WANT TO BE LEADING EDGE ON ISSUES THAT MAY AFFECT OTHER DISEASES BUT WE HAVE HAHN ADVANTAGE THAT COULD PUSH IT FORWARD AND MAKE CHANGES AVAILABLE TO OTHER GROUPS AS WELL. >> AND JUST TO FOLLOW-UP ON THAT, IT WAS BROUGHT UP WE HAVE TO THINK ABOUT WHAT CAN WE ACCOMPLISH VERSUS WHAT MIGHT BE A POLICY ISSUE WHICH WILL TAKE -- REQUIRE VERY DIFFERENT APPROACHES HOW WE WOULD ADDRESS THEM. >> WEES ARE DON'T WANT TO BE BURDENSOME, WE APPRECIATE PARTICIPATION BUT TO YOUR POINT, DR. KATZ, LOOKING AT WHAT IS ACHIEVABLE, WHAT CAN GIVE US A QUICK SUCCESS OR WE CAN MAKE A FAIRLY QUICK IMPACT ON, THAT'S WHAT WE'RE HOPING TO LOOK FOR FIRST. >> LET'S OPEN THIS UP TO OTHERS FOR COMMENTS, QUESTIONS. THOSE ON THE COMMITTEE, FIRST SHOT AT IT. IF YOU'RE SITTING AT THE BACK TABLE. >> THANK YOU AND WE LOOK FORWARD TO THE REPORT AT THE NEXT MEETING SINCE YOU WILL HAVE SOME TELECONFERENCE CALLS. WE'RE GOING TO MOVE ON AND SPEND THE REST OF THE AFTERNOON TO FOCUS ON WHAT I TALKED ABOUT EARLIER THIS MORNING, WHAT WE TALKED ABOUT IN APRIL, THAT IS THE CHALLENGE OF THE ESTABLISH MENT OF NEWLY INDEPENDENT INVESTIGATORS IN THE MUSCULAR DYSTROPHIES. WE HEARD A LITTLE BIT FROM KEVIN THIS MORNING ABOUT WHAT THEY'RE DOING IN IOWA ALONG WITH THEIR WELLSTONE CENTER BUT GETTING UNDERGRADUATES AND MEDICAL STUDENTS INTERESTED IN RESEARCH FIRST AND RESEARCH IN MUSCLE BIOLOGY AND MUSCLE DISEASE, MUSCULAR DYSTROPHIES, IT'S A CHALLENGE, A CHALLENGE TO US AT NIH TO ENRICH THAT TALENTED POOL OF PEOPLE GOING THROUGH MEDICAL SCHOOL AND OTHER PROFESSIONAL SCHOOLS AND TO TURN TO BECOME INTERESTED IN THE MUSCULAR DYSTROPHIES, NOT JUST DERMATOLOGY BUT MUSCULAR DYSTROPHYs. WHAT WE'RE GOING TO DO IS HAVE TWO PRESENTATIONS, KEVIN CAMPBELL FROM IOWA WHO HAS BEEN INTRODUCED APPROXIMATE -- AND KATHRYN WAGNER WHO HAS BEEN HERE BEFORE, TALKED ABOUT HER SCIENTIFIC WORK AT HOPKINS AND WE'LL START WITH KEVIN AND THEN WE'RE GOING TO GO TO KATHRYN WAGNER AND THEN HEAR FROM BOTH TOM CHEEVER AND BY GREG NUCKOLLS WHO WILL PRESENT SUMMARY OF INTERVIEWS WITH MUSCULAR DYSTROPHY AND NEW INVESTIGATORS. >> FIRST I WOULD LIKE TO APOLOGIZE, I WANT TO PUT SOMETHING IN FROM A PREVIOUS TALK THAT I DIDN'T HAVE TIME THE MENTION. JUST TO SHOW YOU HOW THE FAMILY TOUR CAN HELP FAMILY RESEARCH. THIS IS A NICE PROJECT. WHEN AGAIN, THE LAB IS MOSTLY Ph.D.s, SCIENTISTS, BY HAVING THE TOUR THE SCIENTISTS REALIZE MUSCULAR DYSTROPHY PATIENTS ONLY PERFORM MILD EXERCISE. FROMMED ARE PREVIOUSLY YOU WILL SEE, WHEN WE DID EXPERIMENTS WE DID HER SRI EXERCISE BUT MUSCULAR DYSTROPHY PATIENTS ONLY PERFORM MILD EXERCISE. THEY EXHIBIT FATIGUE AND IN THE END OF THE FEATURE WAS BECAUSE OF THIS MOVIE PATIENTS WANT THE FAMILIES AN KIDS TO SEE THE MICE. PREVIOUSLY SOME UNDERSTANDING OF WHAT PATIENTS DID, WE EXERCISE MICE FOR TWO HOURS THROUGH PROTOCOLS, PEOPLE RUNNING MARATHONS BUT THEY REALLY ONLY PERFORM MILD EXERCISE SO WE MODIFIED OUR EXERCISE PROTOCOL AND ALSO DID IT IN THE CYCLE SO THE MICE YOU WERE BAKING UP AND GOING ON A TREADMILL IN THE MIDDLE OF THE NIGHT, WE DID IT DURING THE TIME WHEN THEY'RE NORMALLY ACTIVE. THIS IS THE EXPERIMENT. YOU PUT FOUR MICE ONE CONTROL AND THREE DYSTROPIC MICE INTO A BOX THEY LOOK NORMAL. WHEN WE DID THIS WITH FAMILIES WITH ANIMAL CARE SO WE COULDN'T SHOW THE ACTUAL MITES THEY WOULD SAY THEY DON'T LOOK LIKE DYSTROPIC MICE. THIS IS AFTER TEN MINUTES OF VERY MILD EXERCISE. THESE ARE WILD TYPE, THESE ARE DYSTROPIC. AFTER MILD EXERCISE DYSTROPIC MYSELF SIT THERE. WE KNEW FROM WORKING IN THE LAB BUT MAKING THIS VIDEO WE MADE IT BECAUSE WE WANTED TO SHOW TO IT THE FAMILIES BUT REALIZED ACTUALLY IT WAS A SCIENTIFIC PROJECT HERE. SO MICE EXHIBIT A PHENOTYPE, WE WENT TO STUDY AND QUANTITATE IT, THERE'S A SYSTEM TO MEASURE ACTIVITY AND YOU GET A LOT OF DATA FROM THIS TYPE OF EXPERIMENT, VERTICAL HONSON TALL ACTIVITY AND IF YOU LOOK AT THE ACTIVITY, THESE ARE TWO CONTROL MICE, C 57 MICE, BEFORE EXERCISE, AFTER EXERCISE, AROUND THE SAME AMOUNT OF ACTIVITY BUT THE DYSTROPIC MICE, DND DYSTROPIC DEFICIENT MOUSE THERE'S DRAMATIC REDUCTION IN ACTIVITY WHERE THE FORCE DOESN'T CHANGE THAT MUCH SO IT'S AN INTERESTING PHENOTYPE. WE CONVERTED THIS DATA INTO A SIX MINUTE WALK ASSAY FOR THE MICE. AND YOU CAN SEE CONTROL MICE BEFORE AND AFTER EXERCISE WALKING NICE. DYSTROPIC MICE BEFORE EXERCISE DECREASE AMLATION AS YOU SEE WITH DUE WHICH HE KNOWS PATIENTS AND IF YOU -- DUCHENNE PATIENTS. WE WENT TO STUDY MICE AND FOUND NNOS DEFICIENT MICE HAVE THE SAME PHENOTYPES, IT WAS RELATED TO POLYBLOOD FLOW. BLOOD FLOW IS REALLY IMPORTANT ESPECIALLY AFTER EXERCISE AND CRITICAL TO MAINTAIN BLOOD FLOW AFTER EXERCISE SO GIVE US A CLUE PD 5 INHIBITORS GET INCREASE THE ACTIVITY, AND THIS IS AN EXAMPLE OF PRE-EXERCISE, INHIBITORS IS A NICE INCREASE IN AMBULATION. THIS IS AN EXAMPLE AFTER 30 MINUTES DIFFERENCE BETWEEN TWO MICE, INHIBITORS. KIND OF EXAMPLES TO ILLUSTRATE HOW THE LABS ARE QUITE IMPORTANT BOTH RESEARCH AND TEACHING FAMILIES WHAT'S GOING ON. THAT WENT ON TO A CLINICAL TRIAL WHICH WAS SUCCESSFUL FOR TREATING MUSCULAR DYSTROPHY, BUT CLEARLY I THINK THERE IS SOMETHING TO UNDERSTANDING THE PATHOGENESIS. SO THE TOPIC TODAY FOR ME WAS LOOK AT PROMOTING NEW INVESTIGATORS. I'M COMING AS A PICS WHO INVESTIGATORS, POST DOCS WORK WITH ME AND ALSO AS A CHAIR DEPARTMENT OF PHYSIOLOGY. ONE THING I TELL FACULTY AND NEW DEANS IS WE CAN RECRUIT 100 FACULTY, AND THERE ARE TEN FACULTY YOU CAN PUT IN THE BASEMENT OF A BUILDING WITH NO RUNNING WATER AND THEY WILL BE SUCCESSFUL. THERE'S TEN FACULTY YOU CAN DO EVERYTHING AND THEY'RE NOT GOING TO BE SUCCESSFUL, ONE CHALLENGE IN OUR CAREER IS THAT GOING FROM BEING A GRAD STUDENT POST DOC TO A PI, THERE'S REALLY A DIFFERENT SET OF SKILLS. SO WE HAVE A GOOD EXAMPLE OF A YOUNG FACULTY MEMBER THAT I HELP RECRUIT FROM HARVARD WITH TWO CELL PAPERS. GREAT GUY, NICE GUY ON THE OUTSIDE BUT IF YOU HAD TO WORK FOR HIM, HE'S A TERROR. HE WASN'T SUCCESSFUL, HE CANNOT GET A GROUP TO WORK TOGETHER THOUGH SCIENTIFICALLY HE'S REALLY GOOD AND HE CAN WORK BY HIMSELF BUT TODAY THAT'S DIFFICULT TO DO. SO WHOLE SET OF SKILLS. 80% IN THE MIDDLE THAT'S THE PERCENT WE CAN INFLUENCE BY TRYING TO HELP NEW INVESTIGATORS. THIS IS THE ARTICLE THAT GLENN SENT THAT KIND OF STIMULATED MY THINKING. AND IT SAYS THE YOUNG TALENTED FACULTY ARE REALLY FED UP WITH THE SYSTEM AND GIVES ILLUSTRATION AND READ THIS ARTICLE, OF THREE SCIENTISTS REALLY FED UP WITH THE FUNDING, ALL THE CHALLENGES IN TODAY'S SYSTEM. WHAT I MENTIONED TO GLENN LAST NIGHT, I KNOW A LOT OF YOUNG PEOPLE THAT ARE FED UP WITH THEIR SYSTEM AND IT'S NOT RELATED TO SCIENCE AT ALL. A LOT INVOLVED WITH WORKING 24/7, ALL THE DEMANDS ON ALL THE CONTRACT TYPE WORK, THE DC AREA, I HAVE A DAUGHTER WHO WORKS COMPANY SOLE CONTRACT BASED AND IF YOUR CONTRACTS DON'T GET RENEWED JUST LIKE GRANTS DON'T GET RENEWED WE HAVE A JOB. NOT JUST SCIENCE BUT DEFINITELY IN SCIENCE IT'S CAUSING A MAJOR PROBLEM THAT THE YOUNG PEOPLE ARE GETTING NERVOUS ABOUT STAYING IN SCIENCE AS A CAREER. IT'S NOT THAT BAD. TO ILLUSTRATE THAT, I'M GOING TO SHOW A FEW SLIDES OF WHAT THE POST DOC THAT MY LAB ARE DOING NOW. AND I MADE THIS LITTLE FOUR OR FIVE SLIDES, TEN SLIDES PRESENTATION FOR THE FAMILY MEMBERS. BECAUSE I MENTIONED THAT THEY WERE ALWAYS NERVOUS ABOUT THE POST DOC LEAVING THE FIELD. AND SO THIS IS -- NOW AT THE NEW CASTLE GROUP IN ENGLAND WHO IS WORKING AS A SPECIALIST IN MUSCLE BIOPSIES FOR THAT GROUP. ERIN BEETLE AT UNIVERSITY OF GEORGIA MOVING WITH ERIC HOFFMAN AND RAJU WORKING ON MUSCULAR DYSTROPHY, DANIEL BELTRAND A SCIENTIST IN A GENETICS COMPANY, MICHELLE CROSBY, NOW AT UCLA, A PROFESSOR AND IS WORKING ON MEMBRANE STABILITY AND SKELETON CLIENT MUSCLE IN MUSCULAR DYSTROPHY IN THEIR CENTER AND MADELINE DEBRIS WORKING ON SUFFICIENT MUSCULAR DYSTROPHY. MATT GADERIS NOW AT MILD BRIDGE STARTUP COMPANY WITH A COMPOUND BEING TESTED FOR MUSCULAR DYSTROPHY. AND MENTIONED BEFORE LILY WORKING ON MUSCULAR DYSTROPHY GEN LEVY AT THE CALPAIN FOUNDATION, WORKING IN A PRIVATE FOUNDATION, JESSICA IN SYLVAN'S LAB WORKING AT FSHD AND JAPANESE INVESTIGATORS VERY SUCCESSFUL, DAN MICHAEL WITH MICHIGAN AND ERIC -- AND TACA MORGUCI (PHONETIC). SO THEY ARE ALL BEING SUCCESSFUL AND PROBABLY 85% ARE DOING MUSCULAR DYSTROPHY RELATED RESEARCH. SO NOT AS BAD AS THE ARTICLE MAKES OUT BUT WHEN I SHOW THE SLIDES THAT WAS ALPHABETICAL ORDER. IF I PUT FROM BEGINNING OF MY LAB TO NOW, THE LAST GROUP IS 80, 90% INDUSTRY. THE YOUNG INVESTIGATORS IN LABORATORY ARE NERVOUS ABOUT GOING INTO ACADEMIC POSITIONS. THEY ARE NERVOUS ABOUT FUNDING AND THE DEMANDS THE UNIVERSITY MAKES IN TERMS OF BRINGING IN SALARY FOR -- TO KEEP YOUR POSITION. SO THE COMBINATION OF THINGS IS THEY FEEL THEY CAN'T COMPETE AND FEEL SAFER GOING TO INDUSTRY. IT'S NOT BEEN THAT BAD, THEY'RE STILL WORKING ON MUSCULAR DYSTROPHY BUT WE'RE LOSING A GENERATION OF YOUNG PEOPLE THAT I THINK WOULD MAKE GOOD PROFESSORS BECAUSE OF THE NERVOUSNESS OF THE CURRENT SITUATION HOW TO SUCCEED. I WAS GOING TO TELL YOU THE GENERAL NEEDS FOR NEW INVESTIGATORS BUT I MIGHT JUST START THIS BY GIVING YOU MY STORY WHEN I MOVE THE IOWA. I WAS A POST-DOC IN TORONTO AND I HAD FOUR INTERVIEWS IN THE STATES AND I RECALL WANT TO COME VISIT US AFTER YOUR LAST INTERVIEW. TOLD MY WIFE AND WE BOTH GREW UP IN BROOKLYN, NEW YORK AND I TOLD HIM SHE SAID I DON'T KNOW WHY YOU'RE GOING THERE, I'M NEVER MOVING TO IOWA. AND IT WAS ACTUALLY LUCKY, I THINK IT'S IMPORTANT TO INTERVIEW AT MULTIPLE INSTITUTIONS TO FIND YOUR FIT AT THE END OF THE WEEK I GAFF MY TALK AND FIT IN IOWA. PHYSIOLOGY DEPARTMENT HAD A STRONG MEMBRANE GROUP. THAT'S AN IMPORTANT THING FOR INVESTIGATORS TO FIND, NOT ONLY THE AMOUNT OF MONEY BUT IS IT A GOOD FIT FOR YOU AND WHAT YOU WANT TO DO. SO I MOVED TO IOWA, I HAD NO FUNDING, NO STARTUP PACKAGE. I RAN A GRANT AND GOT $5,000 FOR THE FIRST YEAR. FROM THE FIRST THING I HAD WHICH YOUNG INVESTIGATORS DON'T HAVE TODAY IS TIME. WE GIVE AT IOWA A MILLION DOLLARS SO SOON AS THEY'RE STARTING A BIG LAB, TRYING TO HIRE PEOPLE, THEY DON'T HAVE TIME TO THINK. I SPENT AT LEAST A DAY AND A HALF AT THE LIBRARY THAT FIRST YEAR READING SO THAT'S SOMETHING THAT IS CONTRACTCAL. OLDER PEOPLE LIKE MYSELF SAY WHEN THEY WERE YOUNG THEY HAD IT HARDER AND HAD TO WALK TEN MILES TO SCHOOL AND EVERYTHING ELSE. I THINK I HAD IT EASIER, AT IOWA NO ONE KNEW WHO I WAS, I HAD MY OWN LAB MYSELF. I ALSO VIEWED THE POST DOC AS EQUIVALENT TO THE CHIEF RESIDENTS FOR THOSE HERE WHO ARE PHYSICIANS. CHIEF RESIDENTS AT THE TOP OF THEIR GAME. FROM A PERSON WHO IS A PATIENT, CHIEF RESIDENT IS TOP PERSON IN THE GAME. POST DOC IS THE SAME THING. WHEN YOU TAKE THAT BACK WHEN I SOUGHT IT IN 1980 OR '81, PUT THEM IN A LAB, IT CONTINUES DOING LAB WORK. TODAY WE TAKE THE POST-DOC, STILL IN THE GAME, DOING EXPERIMENTS WRITING MANUSCRIPTS, DOING EVERYTHING AND YOU MOVE THEM TO A NEW LAB, THEN PUT THEM IN THE OFFICE. THEY'RE SPENDING 8 O 0% WRITING GRANTS, DOING ADMINISTRATIVE WORK, NOT DOING LAB WORK, THEY'RE HIRING PEOPLE TO DO LAB WORK SO NOT SETTING UP THEIR OWN LAB, THEY'RE LETTING OTHER PEOPLE DO THAT. SO SOMETHING ABOUT GIVING PEOPLE TIME IS IMPORTANT AND GIVING THEM LAB TIME TO TRANSFER THOSE SKILLS. IF THEY HIRE THREE JUNIOR STUDENTS OR UNDERGRADS OR POST DOC, THOSE PEOPLE ARE SETTING UP THE LAB, NOT THEMSELVES THAT'S A MISTAKE. THE NEXT THING THAT HELPED ME, I WROTE 12 GRANTS THAT YEAR, THREE FUNDED, TWO MOST IMPORTANT WAS MDA AND AMERICAN HEART ASSOCIATION. THOSE WERE CRITICAL FOR MY CAREER, ESPECIALLY AMERICAN HARVEST THREE YEARS AT THE TIME MDA WAS A YEAR, RENEWED IT HELP SOD THE FOUNDATION HELPS KEEP PEOPLE IN THE FIELD BY PROVIDING THAT SUPPORT. IF FOR SOME REASON I WROTE AMERICAN CANCER SOCIETY GRANT, IF THAT WAS FUNDED, I COULD HAVE BEEN DOING CANCER RESEARCH. SO I THINK IT'S IMPORTANT FOR THE FOUNDATION THEY REALLY HELP AT THAT EARLY STAGE TO KEEP PEOPLE IN THE FIELD. SECOND UNOFFICIAL MENTORING, WHATEVER FOR. UNFACIAL MENTORING SO TODAY WE HAVE A OFFICIAL MENTORING AND THERE'S PROPROBLEMS, ONE THEY HAVE A -- THERE'S TWO PROBLEMS, THEY HAVE A COMMITTEE THAT MEETS TWO OR THREE TIMES A YEAR, VERY FORMAL. YOU GET A SENSE THAT'S WHERE MENTORING TAKES PLACE. WHEN I STARTED THERE WAS NO COMMITTEE. YOU MET PEOPLE AT THE MAIL ROOM, IF YOU GET A PAPER REJECTED YOU TALKED ABOUT MORE SENIOR INVESTIGATOR, ABOUT PAPER OR REJECTION OR GRANT. YOU WALKED AROUND THE I WOULD BEING, THERE WAS NO EMAIL SO YOU HAD TO MOVE AROUND A LITTLE BIT MORE. AND SO I THINK THE UNOFFICIAL MENTORING IS MUCH MORE HELPFUL AND COMES IN WHERE THE OFFICIAL MENTORING IS GETTING ME NERVOUS, THE FACULTY TREATED SOMETHING THEY HAVE THE DO. BRO NOT GETTING GOOD ADVICE. THERE'S MORE DEMAND ON THE FACULTY TODAY, FORMER CHAIR GAVE US MONEY TO TRY TO INCREASE ON SOME UNOFFICIAL MENTORING. AT IOWA WHEN I STARTED HERE BEER AND WHICH HE WANTS ON FRIDAY AND IT WAS A GOOD PLACE TO GET MENTORING AT 4 IN THE AFTERNOON. THAT'S NOT ALLOWED ANY MORE BECAUSE OF THE ALCOHOL PART SO HE GAVE US MONEY, WE SET UP A HAPPY HOUR AND THE HAPPY HOUR ALL SENIOR FACULTY SHOWED UP BUT NOT THE YOUNG FACULTY THAT HE RECOLLECTS EAR RUNNING OFF TO PICK UP KIDS AND CHILD CARE. SO IT'S AN IMPORTANT THING TO SOMEHOW GET BACK TO HAVING MORE UNOFFICIAL MENTORING FOR THE YOUNG FACULTY. SUPPORT OF THE POST DOC, THIS IS REALLY CRITICAL. THE MOST IMPORTANT PERSON IN YOUR LIFE WHEN ASSISTANT PROFESSOR IS YOUR FORMER ADVISOR. THEY KNOW YOU, THEY KNOW THE PROJECT, THEY CAN BE EXTREMELY HELPFUL. MY ADVICE WAS DAVID MCCLEAN NONFROM UNIVERSITY OF TORONTO. ONE THING HE TOLD ME ABOUT HAVING A CAREER IN SCIENCE, HE SAID THAT YOU CAN DO AROUND THIS MUCH BUT IF YOU TRAIN 30 PEOPLE, AND THEY ALL DO THIS MUCH, IT WILL AMPLIFY WAY MORE FOR SCIENCE THAN WHAT YOU CAN DO AS AN INDIVIDUAL. AND THE IMPORTANCE OF TRAINING GOOD PEOPLE, AND HELPING THEN, HE WAS HELPFUL FOR ME FOR MYSELF ALL THOSE PEOPLE I MENTION BEFORE, EXTREMELY HELPFUL AND I THINK THAT'S REALLY IMPORTANT. SOME POST DOC ADVISORS ONCE THEY LEAVE THE LAB FORGET ABOUT THEM. I DO THIS -- I THINK I DO IT BECAUSE I LIKE DOING IT BUT ALSO THERE IS SOME PRESSURE ON ME FROM WITH THE HOWARD HUGHES MEDICAL INSTITUTE, MY RENEWAL EVERY FIVE YEARS I HAVE TO GIVE A LIST OF THE LAST 15 YEARS POST-DOC AND WHAT THEY'RE DOING. YOU HAVE A SENSE PART OF THE REVIEW IS HOW WELL WE SEND OUT SCIENTISTS TO THE FIELD. THERE IS SOME THAT'S OUR JOB. NIH COULD DO THAT, THERE'S A LOT OF INFORMATION ON THE POST DOCS YOU'RE PROPOSING BUT LESS INFORMATION WHAT HAPPENS TO THE POST-DOCS THAT YOU HAVE HAD OVER THE LAST TEN YEARS. AND I THINK THAT'S SOMETHING BY PROVIDING A LITTLE PRESSURE THERE WOULD HELP. SOMEHOW THE ADVISORS HAVE TO REALIZE THIS IS IMPORTANT. I THINK YOU SHOULD DO IT REGARDLESS IF THERE'S PRESSURE BUT EVERYBODY IS SO BUSY, ONE ASPECT NICE TO HAVE IS MAKE SURE POST-DOC ADVISORS ARE SUPPORTIVE. WE'LL READ THOSE CRITIQUES AND HELP THEM IN TERMS OF RECRUITING PEOPLE. THE LAST POINT WHICH IS DEFINITELY A PROBLEM TODAY, BUDGETING THE FUND THEY GET. I ONLY HAD $5,000, DIDN'T HAVE THAT MANY PROBLEMS BUT THE NEW INVESTIGATORS WITH A MILLION DOLLAR THINK THEY HAVE A TON OF MONEY. EVERY TIME I SIT DOWN AND EXPLAIN IF YOU TAKE ONE GRAD STUDENT TODAY IT RUNS AROUND 30, $40,000 PER GRAD STUDENT, WITH BENEFITS AND EVERYTHING ELSE. IF THEY STAY FOUR, FIVE YEARS THAT'S 150, $200,000, SO 20% START UP THERE. MOST TIME YOUNG INVESTIGATORS WANT TO GET GRAD STUDENTS SO THEY'RE OUT THERE RECRUITING LIKE CRAZY AND THEY END UP WITH THREE GRAD STUDENTS, SO THERE'S $500,000, HALF THEIR STARTUP IS GONE ON THESE GRAD STUDENTS. SO IF THEY REALLY NEED FISCAL MANAGEMENT. WE JUST HAD ONE YOUNG INVESTIGATOR START THE LAB, HIS BOSS IS NOW THE HEAD OF THE LIFE SCIENCE INSTITUTE AT MICHIGAN, HAS LOTS OF MONEY. WE FOUND OUT HE WAS SPENDING $17,000 A MONTH ON MICE. HE HAD NO IDEA THAT HIS STARTUP WAS JUST GOING TO DISAPPEAR, HE WAS DOING SOMETHING LIKE HIS BOSS WOULD DO. ANOTHER THING I'M TELLING PEOPLE WHEN YOU START YOUR OWN LAB AND IF YOU WANT TO LOOK AT YOUR FORMER BOSS, LOOK AT WHAT YOUR FORMER BOSS, WHAT SHE -- HE OR SHE DID WHEN THEY STARTED DILUTED SHARE LAB, NOT WHAT THEY DO NOW. IF YOU'RE COMING FROM A LAB WITH A LOT OF MONEY AND THEY CAN HAVE MICE OR THEY CAN SPEND $15,000 A MONTH YOU REALLY CAN'T DO THAT. SO YOU HAVE TO LOOK AT THE FINANCES OF A SMALL LAB AND YOU HAVE TO BE REALLY -- THE SCIENCE IN TERMS OF THE PROJECTS YOU PICK TO SUPPORT THOSE. TOO MANY YOUNG PEOPLE ARE GETTING IN TROUBLE, THEY SPEND ALL THE STARTUP MONEY AND THEN THEY HAVE NOTHING TO SHOW FOR IT. SO THAT'S SOMETHING THAT'S REALLY IMPORTANT. SO THOSE ARE THINGS THAT HAPPEN TO ME. AFTER THE FIRST YEAR I WENT ON TO THE FIRST RO1 GRANT BUT THE FIRST YEAR AND A HALF ARE CRITICAL. ALSO BECAUSE I HAD SO FEW FUNDS I HIRED ONLY A FEW PEOPLE ONE STUDENT AFTER FIRST YEAR THEN TWO STUDENTS AND THREE, FOUR YEARS LATER I ONLY HAD THREE PEOPLE. I THINK THAT'S OOH AN IMPORTANT THING YOU NEED THE BUILD SKILLS OF RUNNING LAB, MANAGING PEOPLE. COMING FROM A POST-DOC LAB YOU HAVE LOTS OF FRIENDS, THE FIRST INSTINCT IS BE FRIENDS WITH PEOPLE IN THE LAB. THEY WERE A POST-DOC AND FRIENDS WITH EVERYBODY IN THE LAB, SOME POINT YOU HAVE TO REALIZE YOU HAVE TO BE THE BOSS. IF YOU'RE A FRIEND IN THE LAB, THINGS WILL WORK OUT. SO YOU HAVE TO TAKE RESPONSIBILITY SO THAT'S ANOTHER THING YOU SHOULD DO DURING THAT TIME. THE SPECIAL NEEDS THINKING INVESTIGATORS TODAY. SO WHEN I STARTED THE CRITICAL REAGENT FOR ME FOR THE AMERICAN HEART ASSOCIATION GRANT CAME FROM THE MEDICAL SCHOOL DOG LAMP. THIS WAS ALSO SOMETHING I BELIEVE IN, YOU SHOULD BE INVOLVED IN TEACHING AND I VOLUNTEERED TO HELP WITH THE DOG LAMP, AT THAT TIME, DID YOU HAVE THE DOG LATCH IN MEDICAL SCHOOL? NO? YOU DID? SO IT WAS ALMOST REQUIRED FOR EVERYONE AND NOW THERE'S NO DOG LABS LEFT. THERE'S A CARDIOVASCULAR LAB AND IT'S I THOUGHT AND IMPORTANT LABORATORY EXPERIENCE WITH MEDICAL STUDENTS BUT WE HAD 180 MEDICAL STUDENTS, SIX PER DOG SO IT WENT A FEW WEEKS AND I HELPED OUT. THE FIRST TIME THEY WERE TAKING THE DOGS DOWN TO THE INCINERATOR, THESE ARE ALL STRAYS BUT BASICALLY I SAID YOU KNOW NEXT TIME CAN I HAVE THE HEART? AND THEY SAID SURE. SO I GOT THE HEARTS AND MADE CARDIAC MEMBRANES. IT WAS CRITICAL FOR MY CAREER. I HAD ENOUGH CARDIAC MEMBRANE TO LAST A COUPLE OF YEARS AFTER THAT COUPLE OF WEEKS OF COLLECTING DOG HEARTS. THAT WAS A CRITICAL REAGENT FOR ME BECAUSE THERE WEREN'T ANIMAL MODELS BUT TODAY THE ANIMAL MODELS ARE CRITICAL FOR THE YOUNG INVESTIGATORS. AND THEY HAVE TO BE AVAILABLE WITH NO STRINGS ATTACHED. THERE'S TOO MANY PEOPLE WHO SAY I'M NOT GOING TO GIVE THEM TO JACKS BECAUSE I'LL GIVE OUT THE MONEY. WHAT THEY REQUIRE ADS YOUNG PERSON, I WOULD LIKE TO HAVE YOUR SPECIAL MICE AND THEN THEY GO WHAT DO YOU WANT TO DO WITH THEM? IT RUNS INTO CONFLICT. HAVING THEM TO REORDER, SAME WITH ANTIBODIES AND EVERYTHING ELSE. SO THAT'S SOMETHING THAT HELPS YOUNG INVESTIGATORS WHEN THERE'S NO STRINGS ATTACHED TO THE -- ESPECIALLY THE ANIMAL MODELS SALARIES ARE NOW HIGHER AND FACULTY ENCOURAGES 350% SALARY OR MORE. -- 50% SALARY OR MORE. IT WOULD BE NICE THE YOUNG INVESTIGATORS THE FIRST SIX YEARS, UNIVERSITIES WERE TOLD THEY SHOULDN'T BRING IN ANY SALARY, TO FREE THEM UP FROM THAT BURDEN, IT TAKES A BIG CHUNK OF THEIR RO1 GRANT, GOES TO SALARY SUPPORT, AND THEY ARE STILL WORRIED ABOUT MAINTAINING SALARY SUPPORT. IN CANADA YOU DON'T HAVE TO BRING IN SALARY, IN EUROPE PLACES TO BRING IN SALARY, THAT'S SOMETHING THAT'S HARD TO CHANGE MAYBE ONCE ASSOCIATE PROFESSOR THAT COULD BE DIFFERENT BUT THE YOUNG PEOPLE, IT WOULD BE REALLY NICE TO REMOVE SALARY SUPPORT BECAUSE IT'S A BURDEN FOR THEM AND THEY'RE CONCERNED AND THAT ARTICLE ALSO THE YOUNG PEOPLE ARE VERY CONCERNED ABOUT MAINTAINING THEIR SALARY. OFFICE AND LAB ADMINISTRATIVE SUPPORT. THIS IS CRITICAL. SET UP A LAB TAKES SO MUCH DIFFERENT SETS OF PAPERWORK IN TERMS OF THE ENVIRONMENTAL SAFETY, ANIMAL CARE PROTOCOLS, A WHOLE SERE RES OF THINGS THAT -- SERIES O THINGS, UNLESS YOU HAVE ADMINISTRATIVE SUPPORT YOU SPEND MOST TIME IN THE OFFICE DOING THIS WORK AND YOU HAVEN'T BEEN TRAINED THAT WELL WITH DOING IT. I SUGGESTED ONCE TO OUR DEAN WE HIRE SOMEBODY THAT WOULD MANAGE THREE OR FOUR YOUNG INVESTIGATORS TO DO THIS WORK. HELP WITH ENVIRONMENTAL SAFETY, CHEMICAL HAZARD, ALL THE THINGS YOU HAVE TO DO BUT NOT SUPPORT BECAUSE THERE'S NOT MONEY TO DO THAT BUT IT'S NEEDED TODAY BECAUSE IT REALLY HURTS THE YOUNG INVESTIGATORS. LAB MANAGE MENTORING HOW TO RUN A LAB WHAT TO DO, WHAT YOU SHOULD TELL -- WHAT TO TELL STUDENTS AND POST-DOCS. WE NOW AT IOWA HAVE MANUSCRIPT AND GRANT EDITING SERVICES SO SERVICES THAT HELP IN TERMS OF MANAGEMENT, HELPING WITH MANUSCRIPTS AND GRANTS. ALMOST EVERY ONLINE MANUSCRIPT SHOULD BE EASIER TO DO TODAY BUT THEY'RE ALL MUCH MORE COMPLICATED TOO DO. SAME THING WITH GRANTS. SO THAT'S SOMETHING THAT REALLY HELPS THE YOUNG FACULTY. THIS LAST POINT, HALF THE PEOPLE IN SCIENCE TODAY ARE FEMALE FACULTY. HAVING EXCELLENT CHILD CARE, HELPFUL FOR MALE AND FEMALE. SOME OF MY MALE FACULTY ARE DOING CHILD CARE. AT IOWA WE STILL REALLY ONLY HAVE ONE GOOD CHILD CARE FACILITY CLOSE TO THE RESEARCH BUILDING. IT'S INTERESTING HOWARD HUGHES MEDICAL INSTITUTE WHEN THEY MADE RESEARCH FACILITY OUT IN LEASEBURG THEY BUILT CHILD CARE INTO THE BUILDING WHICH IF YOU'RE NURSING MOM YOU COULD GO THERE, RIGHT IN THE RESEARCH BUILDING. AND THEY ALSO HAVE REALLY GOOD CARE. ONE PROBLEM WITH IOWA, I HAVE A DAUGHTER WHO LIVES HERE, WHO HAS REALLY GOOD CHILD CARE, AND THEY PROVIDE A LOT OF SERVICES WHERE IN IOWA YOU HAVE TO GET THERE BY FIVE O'CLOCK AND ALL THE EXTRACURRICULAR ACTIVITIES YOU HAVE TO DO SO YOUNG SCIENTISTS FEMALE SCIENTISTS, THEY'RE RUNNING AROUND ALL DAY LONG AFTER THEY GET DONE. AND SO I THINK HAVING EXCELLENT CHILD CARE IS NEEDED SINCE HALF THE WORK FORCE IS NEEDING THAT. AND PROBABLY THE OTHER HALF IS GOING TO USE IT TOO. SO THOSE ARE THINGS WE CAN DO TO HELP OUT, IF WE HAD MORE MONEY IN THE SYSTEM, THAT WOULD REALLY HELP. SO THE FINAL TWO POINTS I WOULD LIKE TO MAKE IS ONE THAT I THINK THE TITLE OF MY TALK SHOULD HAVE BEEN YOUNG INVESTIGATORS. THIS MIGHT NOT BE LEGAL BUT TO BE HONEST I STARTED AT IOWA, I WAS 28. I DIDN'T DO ANYTHING SPECIAL, IT WAS THE AGE A LOT OF FACULTY STARTED THEIR LABORATORIES. 28 TO 35 OR SO, YOU HAVE LESS PROBLEMS, LESS -- YOUR PARENTS ARE HEALTHY, YOU USUALLY -- MIGHT IN THE HAVE KIDS YET. YOU JUST -- THERE'S A SERIES OF THINGS THAT MAKE YOU MORE PRODUCTIVE. MATH THEY SAY YOU DO MOST WORK REALLY GOOD WORK BEFORE 30. I THINK THE SAME IS TRUE IN SCIENCE. AND TODAY LOT OF INVESTIGATORS WE'RE HIREK NOW ARE 40, 42. AND THERE'S A BIG DIFFERENCE BETWEEN 28 AND 42. THAT HURTS THE WHOLE SYSTEM, SOMEHOW WE HAVE TO PUSH THE SYSTEM BACK. THIS IS WHERE NIH I THINK WOULD HELP ALSO. THE REASON WHY UNIVERSITIES GO AFTER POST-DOCS TEN YEARS, THEY WANT PEOPLE THAT WILL GET FUNDED. NIH, SAID THERE WAS A NEW RO1 NEW INVESTIGATORS BUT ONLY AFTER FIVE YEARS POST-DOC. UNIVERSITIES WOULD RESPOND. THEY HIRE PEOPLE THAT COULD BE COMPETITIVE FOR THOSE AWARDS. SOMEHOW WE HAVE TO CHANGE THE SYSTEM SO WE GET PEOPLE STARTED IN LABS AT MUCH MORE REASONABLE AGE. THAN 42. THAT IS BOTH CLINICAL SHEENSES I THINK IS EVEN MORE -- SCIENCES IS MORE A PROBLEM BUT DEFINITELY BASIC SCIENTISTS EXTENDING EXTENDING EXTENDING. LAST POINT WAS THERE IS ANOTHER PROBLEM WE HAVE IN THE SYSTEM, THE NEWLY ESTABLISHED INVESTIGATORS. DEPARTMENT OF PHYSIOLOGY AND BASIC SCIENCES AT IOWA, LOOK AT THE UNFUNDED FACULTY, ALL HAVE HAD ONE RO1 GRANT. IF YOU LOOK AT FUNDED FACULTY TODAY, YOU FIND THAT ALL OF THEM HAVE HAD SOME TIME IN THEIR CAREER TWO RO1 GRANTS SO THERE'S A BIG DIFFERENCE GETTING THE SECOND RO1, IT ESTABLISH AS PROGRAM, ALLOWS THE PEOPLE TO DO MORE ANDSYMES THEY ONLY HAVE THAT SECOND RO1 TWO OR THREE CYCLES BUT THOSE FACULTIES MOVE TO A DIFFERENT LEVEL. THEY STAY FUNDED THEIR CAREER. THE FACULTY MEMBER THAT HAS RO1 AND LOSES IT, IT'S ALMOST IMPOSSIBLE TO COME BACK. WE HAD THREE DEANS WITH NEW PROGRAMS TO RESCUE FACULTY. NONE WORK. IT'S JUST -- I DON'T KNOW IF IT'S THE SYSTEM, GRANT REVIEW SYSTEM BUT SEEMS IF YOU HAVE THAT RO1 AND HAVEN'T HAD FUNDING THREE OR FOUR YEARS YOU WON'T GET BACK INTO THE RESEARCH SYSTEM. THAT'S AN IMPORTANT SYSTEM WE'RE ALSO WE NEED TO THINK ABOUT IS HOW TO KEEP THESE NEWLY ESTABLISHED INVESTIGATORS GOING SO THEY GET A WHOLE PROGRAM GOING. I'LL END THERE AND TAKE QUESTIONS. [APPLAUSE] >> FROM ONE COMMENT, ONE QUESTION. I AGREE WITH VIRTUALLY EVERYTHING YOU SAID, TIME IS THE -- IS THE -- IT'S THING THAT ACTUALLY IN THE INTRAMURAL PROGRAM I CAN SAY THAT'S THE THING THAT ALL OF US COVET IS THE TIME WE HAVE. I THINK STARTING A LAB THAT IS TOO LARGE IS A PROBLEM BECAUSE YOU WANT EVERYBODY TO BE SUCCESSFUL. YOU DON'T REALIZE THAT A LOT IS NOT GOING TO BE SUCCESSFUL. BUT TWO POINTS FROM THE NIH INSTITUTIONAL STANDPOINT. ONE, WE HAVE CONTRIBUTED, WE WHEN I SAY WE, THE NIH CONTRIBUTED ALONG WITH THE COMMUNITY TO THIS IDEA THAT THE FIRST RO1 COMES IN THE LATE 30s OR AVERAGE AGE, 42. OR 43. BECAUSE THE EXPECTATION NOW IS OKAY, YOU DO ONE POST DOC, YOU DO ANOTHER POST-DOC, YOU GET A K AWARD AND BY THAT TIME, YOUR 11 YEARS, 12 YEARS AFTER YOUR Ph.D. OR M.D. OR SPECIALTY TRAINING. ONE THING TO QUESTION YOU ON WE VIEW NIH WIDE NOW, IF WE HAD MORE MONEY, IT WOULD BE OKAY. SO I THINK IT IS TRUE. WE HAVE BEEN FIGHTING MANY YEARS WHEN YOU CONSIDER PLACES WE HAVE BEEN, DOWN 20%. THE QUESTION IS, WHAT WE CAN DO WITH THAT MONEY. DO YOU INVEST IN MORE INVESTIGATORS OR DO YOU INVEST IN PROVIDING INVESTIGATORS WITH MORE MONEY? THAT IS THE QUESTION. WE DON'T KNOW HOW TO PREDICT WHO WILL BE, AND WHO WILL NOT BE SUCCESSFUL. >> >> BUT IT'S BEEN 250K PROBABLY 20 YEARS NOW. >> IT'S -- I CAN SAY 20 YEARS AGO. >> CLEARLY THE FACULTY THAT STARTED 20 YEARS AGO AT IOWA WAS GETTING $40,000 AND NOW SALARIES $80,000. IF YOU LOOK AT THEIR SALARY, LOOK AT THE OTHER SALARIES THEY HAVE GONE UP, EVERYTHING ELSE HAS GONE UP SO MUCH SO, THAT SAME 250K IS VERY WELL. SO THAT'S AN IMMEDIATE PROBLEM WE'RE GIVING A GRANT BUT ONCE THEY SAW PAYING SALARY, FRINGE BENEFITS AND -- BUT THEY DON'T HAVE MUCH MONEY TO WORK WITH SO THAT'S WHERE WE NEED MORE MONEY. TO BE REALISTIC GIVE THE SAME DOLLAR EQUIVALENTS YOU DID 20 YEARS AGO. >> SO THEN THE QUESTION IS, WHAT IS THE VALUE OF RETURN BEYOND TWO OR THREE RO1s? FIVE RO1s? >> I WOULD SAY -- I THINK PRODUCTIVITY GOES UP AS YOU INCREASE IN RESEARCH DOLLARS. >> CLEARLY IOWA THERE'S PEOPLE THAT SPEND ALL THEIR TIME GETTING RESEARCH, VERY GOOD GETTING GRANTS AND SPEND ALL THEIR TIME AND PUBLICATION WISE NOT DOING ADS WELL. >> FROM THE DATA BEARS THAT OUT THERE'S A CERTAIN POINT OF NO ROW LESSER RETURN, I WON'T SAY NO RETURN. QUESTIONS OR COMMENTS? NOW WE'RE GOING TO HEAR FROM DR. WAGNER WHO IS AT HOPKINS WHO HAS -- ALSO TRADITION OF NOT QUITE AS LONG A TRADITION AS DR. CAMPBELL BUT TERMS OF TRAINING AND SHE WILL PROVIDE PERSPECTIVE OF PROMOTING NEW INDEPENDENT PHYSICIAN SCIENTISTS. >> FROM I APPRECIATE THE INVITATION. AND I APPRECIATE THE ATTENTION THE COMMITTEE IS SPENDING ON IT. AND THERE ARE NOT ENOUGH PEOPLE DOING WHAT I AM TRYING TO DO ESSENTIALLY DO CLINICAL RESEARCH AND MUSCULAR DYSTROPHIES. WITH ALL THE DRUGS IN THE PIPELINE FOR MUSCULAR DEMENTIA WE NEED TO GROW THE -- DYSTROPHY WE NEED TO GROW THE FIELD. I LEFT MY MOUSE SLIDES AT HOME BUT MY MICE ARE BIGGER AND MORE MUSCULAR THAN KEVIN'S MICE. >> THEY HAVE TO BE IN BALL MORE. >> SO I THOUGHT IT HELPFUL TO REVIEW WHAT TRAINING OF A NEUROLOGIST PHYSICIAN SCIENTIST IS LIKE. NOT ALL ARE NEUROLOGISTS, SOME ARE SPECIALISTS, FOR EXAMPLE, CARDIOLOGIST BUT THE MAJORITY ARE NEUROLOGISTS. THIS IS AFTER GETTING AN M.D. OR M.D. Ph.D.. SO AT THE AGE OF 26 OR 30, THEY SPEND A YEAR IN MEDICAL INTERNSHIP AND THREE IN NEUROLOGY RESIDENCY, THEN ONE TO TWO YEARS IN MUSCULAR DYSTROPHY FOLLOWSHIP. AND THEN THEY MAY SPEND ANOTHER COUPLE OF YEARS WITH ADDITIONAL FELLOWSHIP NEUROGENETICS OR IN A MUSCULAR DYSTROPHY FELLOWSHIP. THEN SOME PARTICULARLY THOSE WHO HAVE M.D. Ph.D. MAY DO LABORATORY POST-DOCTORAL FELLOWSHIP FOR A FEW YEARS. AS YOU CAN SEE, THIS ACCUMULATES TO A MINIMUM OF FOUR YEARS AFTER POST GRADUATE DEGREE BUT OFTEN FOR A FULL DECADE. THAT'S REALLY IMPORTANT. BECAUSE IT SHAPES WHY WE LOSE SOME OF THESE PEOPLE, BECAUSE OF THE LENGTH OF THE TRAINING. AND THESE ARE PLACES WE LOSE. SO ONE PLACE HERE IS RIGHT AFTER ALL THE CLINICAL TRAINING, THERE'S LOSS OF PERSONNEL AND I THINK THAT THAT IS -- IT'S BEEN A WHILE SINCE YOU HAVE BEEN IN LAB OR HAVE HAD ANY RESEARCH OR HAD ANY AWE TON MY. AND YOU WILL YOUR PEERS MANY PIERCE GO OFF AND GET SALARIES THAT ARE TWICE BEING OFFERED TO YOU TO STAY IN ACADEMIA. SO THIS IS TIME PEOPLE DROP OUT. ANOTHER TIME PEOPLE DROP OUT IS THEY HAVE DONE LABORATORY POST-DOCTORAL FELLOWSHIP THEY FIND TOO HARD, FOR INSTANCE THEY GOT A Ph.D. AND NOW TRYING TO GET BACK INTO THE LAB AND THEY JUST WITH THE NUMBERS OF YEARS THAT ELAPSED, JUST TOO HARD FOR THEM AND THEY'RE DISCOURAGED. SO THEY GO BACK TO STRAIGHT CLINICAL WORK. FROM SOME THINGS REPEATED BETWEEN MY FAULK AND KEVINS. WHAT'S NEW IN TERMS OF SCIENTISTS NEED, THEY NEED TIME, MONEY, TRAINING MENTOR SHIP, EXPOSURE AND I'M GOING THE TALK EACH OF THESE. AND NAY NEED LUCK WHICH I WON'T TALK ABOUT BECAUSE IT'S TOO ELUSIVE. SO TIME. DIFFICULT ACADEME IN ADDITIONS AND SCIENTISTS -- ACADEMICIANS AND SCIENTISTS HAVE OUTPATIENT CLINIC THEY'RE AWARDED 10% EFFORT. THEY MAY HAVE OTHER INPATIENT RESPONSIBILITIES BIOPSY READING THEY GET ANOTHER FIVE TO 15% EFFORT AND HOPEFULLY THAT LEADS THEM WITH PROTECTED RESEARCH TIME OF 75 TO 85%. THIS IS ALL ALSO ASSUMING THEY HAVE MONEY WHICH I'LL GET TO. BECAUSE I DON'T KNOW ANY OTHER SYSTEM OTHER THAN MONEY WHERE YOU BRING IN THE MONEY THAT GIVES YOU THE 75 TO 80% EFFORT. BUT EVEN SO, WHEN STARTING OFF, YOU ARE NOT VERY EFFICIENT SO HALF DAY CLINIC YOU MAY SAY THAT'S FOUR OR FIVE HOURS, WELL, THAT DOESN'T ACTUALLY TRANSLATE TO A 40, 50 HOUR WORK WEEK BECAUSE HALF DAY CLINIC PAYS YOU MORE LIKE TEN HOURS GIVING YOU EITHER AT 80 OR 100 HOUR WORK WEEK OR MORE LIKELY BITING INTO THIS PROTECTED RESEARCH TIME. WRONG BUTTON. SO MONEY, WE EEL HEAR MORE FROM TOM AND GLENN ABOUT VARIOUS WAYS IN WHICH YOUNG PHYSICIAN SCIENTISTS PAY FOR THEMSELVES. BUT THE ONE MECHANISM THAT IS EXTREMELY HELPFUL ARE THE MENTOR K AWARDS, THE DO 8 FOR LABORATORY BASE K 23 CLINICAL RESEARCH BASE, COVERS $100,000 SALARY PLUS 30,000 OR 51,000 AT NINDS. AND NINDS HAS A BRIDGE FUNDING K O 2 IN PEOPLE WHO HAD K 23 OR KO 8 BEFORE THEIR RO1 BUT THIS PROVIDES SIMILAR FUNDING. NOW, THE MDA HAS DEVELOPMENT GRANTS THAT WE HEARD ABOUT EARLIER WHICH IS $60,000 A YEAR. FROM AND AAN HAS A CLINICAL RESEARCH FELLOWSHIP IN MUSCULAR DYSTROPHY. $55,000 A YEAR PLUS $10,000 FOR RESEARCH SUPPLIES. THESE ARE REALLY ONLY -- THESE ARE HELPFUL, VERY HELPFUL, I THINK THEY ENCOURAGE PEOPLE TO ENTER THE FIELD BUT CAN'T BE, AND YOU CAN DO THE MATH, THEY CAN'T BE USED ALONE, THEY CAN'T BY THEMSELVES FUND SOMEONE AND IN FACT THE MDA DEVELOPMENT GRANTS ARE FREQUENTLY PAIRED WITH THE K AWARDS, I DON'T REMEMBER WHETHER THE AAN YOU CAN DO THAT WITH THE K AWARD. FROM OTHER FOUNDATIONS HAVE GRANTS NOT SPECIFIC FOR DEVELOPMENT BUT CERTAINLY HAVE BEEN GIVEN TO YOUNG CLINICIAN SCIENTISTS, SUCH ADS PTMD AND TODAY'S SOCIETY ALWAYS HAS NUMBER OF YOUNG INVESTIGATORS, AND THERE ARE GRANTS TO MENTOR OR INSTITUTIONS SUCH AS T-32. >> IF YOU DON'T MIND INTERJECTING HERE, THERE'S VERY MUCH IN COMMON WITH NIMS AND NINDS HAVE, THAT IS, AND PRETTY MUCH ACROSS THE NIH PEOPLE MIGHT NOT KNOW THE SUCCESS RATE OF PEOPLE WHO HAVE KO 8 AWARD IS 50% OPPOSED TO -- >> MY NEXT SLIDE. NOT QUITE 50% BUT HIGH. SO ABOUT A THIRD OF APPLICANTS HAVE FUNDING. >> I WILL TELL YOU THOSE WHO APPLY, OBVIOUSLY IF YOU DON'T APPLY YOU CAN'T GET IT BUT THOSE WHO APPLY THE SUCCESS RATE IS CLOSE TO 50%. >> I'M NOT SURE HOW THE NUMBERS DIRE, THESE ARE THE NUMBERS OFF THE NIH WEBSITE OF THE SUCCESS RATE OF -- FROM NIAMS. >> ARE YOU FUNDING SUCCESS RATE IF THEY APPLY AND HAVE TO RESUBMIT THAT COUNTS AS ONE SUCCESS? >> WHAT I'M SAYING IS PEOPLE WHO HAVE KO 8 AWARDS OF THOSE WHO APPLY FOR RO1 ALMOST 50% SUCCESSFUL. >> I DIDN'T UNDERSTAND YOU WERE TALKING RO1s. OKAY. SO THE SUCCESS RATE OF K AWARDS, IT'S CERTAINLY A LOT HIGHER THAN RO1s IN GENERAL. THIS IS -- >> YOU WERE JUST TALKING ABOUT THE SUCCESS GETTING A K AWARD. I WAS TALKING ABOUT HOW -- THAT K AWARD IS TO ULTIMATE SUCCESS, IF YOU MEASURE BY RO1 SUCCESS. >> RIGHT. OKAY. SO HOPKINS HAS HIGHER SUCCESS RATE AND MANY SAID THAT'S DUE TO BIAS OF THE PROXIMITY OF BALTIMORE TO BETHESDA. BUT I -- >> TRUST ME, IT'S NOD. >> WHAT I THINK IS IT IS IS HOPKINS HAS TO GO THROUGH A RIGOROUS INTERNAL PROCESS, MY MENTOR WHO HAS A K 23 SUBMITTED HER GRANT FOR TWO CYCLES TO THE INTERNAL REVIEW. WHERE THEY TORE IT UP AND REALLY TOLD HER, DON'T SUBMIT. SHE COULD HAVE SUBMITTED ANYWAY BUT THEN SHE WOULDN'T HAVE GOTTEN HER LETTER FROM THE CHAIRMAN. SO IT HOLDS BACK APPLICATIONS UNTIL THEY ARE THOUGHT TO BE SUCCESSFUL. SO TRAINING. MANY PEOPLE THINK THAT IF YOU'RE A GOOD CLINICIAN THEN YOU WILL AUTOMATICALLY MAGICALLY BECOME A GOOD CLINICAL RESEARCHER AND IT'S REALLY NOT TRUE, IT IS SPECIAL SCIENCE IN THE SAME WAY THAT MOLECULAR BIOLOGY IS AND PEOPLE NEED TO BE TRAINED IN THE METHODS OF CLINICAL RESEARCH. THERE ARE A FEW PLACES THAT I KNOW OF THAT DO THIS WELL, HOPKINS HAS THE SCIENCE OF CLINICAL INVESTIGATION WHERE YOU CAN GET A CERTIFICATE, A MASTERS OR A Ph.D.. DEPENDING ON THE DEPTH OF WHAT YOU DO, HARVARD HAS A SIMILAR CLINICAL INVESTIGATION AND UNIVERSITY OF ROCHESTER HAS A FELLOWSHIP IN EXPERIMENTAL THERAPEUTICS. I'M SURE MANY OTHERS BUT THOSE ARE FEW I KNOW OF THAT ARE VERY GOOD. WHAT THESE DO IS GIVE YOU STATISTICAL BACKGROUND TO CONDUCT AND INTERPRET CLINICAL TRIALS, HELP YOU UNDERSTAND VARIOUS DESIGNS OF CLINICAL TRIALS AND WHICH IS APPROPRIATE AND CERTAIN SETTINGS HELP WITH LEARNING DATA ENTRY AND MANAGEMENT AND THE ETHICS OF CLINICAL TRIALS WE HEARD EARLIER TODAY. AND THERE'S A SEPARATE SIDE OF TRAINING IN CLINICAL RESEARCH, THE NUTS AND BOLTS YOU DON'T GET IN A COURSE BUT YOU MIGHT GET IN A FELLOWSHIP WHERE YOU WERE A FELLOW DOING CLINICAL TRIALS UNDER A MENTOR. SO THIS IS PUTTING IN IRB APPLICATIONS, SUCCESSFULLY SO THAT YOU'RE NOT WASTING TIME GOING BACK AND FORTH WITH IRB, NEGOTIATING CLINICAL TRIALS, BUDGETING AND LEARNING RECRUIT MENT OF SUBJECTS FOR TRIALS. THERE IS THE PROJECT SPECIFIC EDUCATION SO IF YOU'RE FOR INSTANCE LIKE MY CURRENT MENTEE DOING CLINICAL STUDIES IN MRI AND HAVING THE APPROPRIATE BACKGROUND TO BE ABLE TO CONDUCT THOSE TRIALS. FROM SO MENTORSHIP IS CLEARLY A MAJOR NEED OF THE YOUNG CLINICIANS SCIENTISTS, AN IMPORTANT FEASIBLE LINE OF INQUIRY IS THE MOST IMPORTANT THING FOR A YOUNG INVESTIGATOR. GIVING ADVICE ON PUBLICATION AND GRANTS, INTRODUCING THE JUNIOR INVESTIGATOR TO NETWORKS OF COLLABORATORS. AND PROMOTING THE JUNIOR INVESTIGATORS OR BOTH INTERNALLY AND EXTERNALLY. IN TERMS OF EXPOSURE, I THINK THIS IS SOMETHING THAT WE CAN DO MORE OF TO HELP OUR JUNIOR INVESTIGATORS. THIS CAN BE A NATIONAL AND INTERNATIONAL MEETING OPPORTUNITIES TO GIVE GRAND ROUNDS, PUBLICATIONS AND PROMINENCE AUTHOR ORDER OF PUBLICATION, PARTICIPATING IN STUDY SECTIONS AND REVIEW, CONFERENCE ORGANIZATIONS, PROFESSIONAL SOCIETY LEAD SHIP ROLES AND COMMUNITY OUTREACH ADVOCACY. SO WHY DO TRAINEES DROP OUT OF RESEARCH? LONG YEARS OFFER TRAINING, ALSO MENTIONED THE TRANSITION FROM CLINICAL WORK TO RESEARCH AS A TIME WHICH MANY PEOPLE DROP OUT. THE LACK OF'SLY ACCESSIBLE PRELIMINARY DATA IN CLINICAL RESEARCH IS MUCH LESS EASY I THINK TO BE ABLE TO GENERATE CLINICAL DATA THAN LABORATORY DATA. PARTICULARLY FROM GROUND ZERO THERE MAYBE -- WE TALKED ABILITY DATABASE SHARING OR DATA SHARING, THERE MAYBE WAYS WE CAN MAKE THIS MORE EASY FOR JUNIOR INVESTIGATORS TO BE ABLE TO LOOK AT PRE-EXISTING DATA TO DEVELOP HYPOTHESES. DIFFICULTY DIFFERENTIATING ONE'S SELF FROM THE MENTOR, I THINK IS ALSO VERY DIFFICULT IN CLINICAL RESEARCH. THERE ARE MANY FEWER PUBLICATIONS OUT OF CLINICAL RESEARCH AND HAVING AN ENTIRELY DIFFERENT ROLE FOR MENTOR IS DIFFICULT. WE TALKED ABOUT THE DIFFICULTY OF JUMPING FROM THE FIRST MENTOR AWARD TO RO1 OR EQUIVALENT. CAN EXPOSE FELLOWS TO MUSCULAR DYSTROPHY THROUGH LECTURES LABS CORNSES AN MENTOR JUNIOR INVESTIGATOR AS DESCRIBED ABOVE. FOUNDATIONS CAN ESTABLISH AND FUND ADDITIONAL DEVELOPMENT MENTORED RESEARCH AWARDS, AND THEY CAN ALSO DO SOME FUNDING OF REGISTRATION AND TRAVEL TO CONFERENCES AT THE FSH SOCIETY MEETING OR INTERNATIONAL FSH RESEARCH MEETING DAN SPOKE ABOUT, THERE WERE A NUMBER OF JUNIOR PEOPLE WHO SPOKE THERE. THAT'S A WONDERFUL VENUE TO BE ABLE TO GIVE PEOPLE EXPOSURE. THE NIH COULD INVEST NOR K AWARDS, THE SUCCESS RATE IS GOOD BUT IT COULD BE BETTER. I THINK THAT MONEY IS WELL SPENT. KEVIN MAY KILL ME FOR THIS ONE BUT ONE COULD ADD A JUNIOR PHYSICIAN SCIENTIST, ONLY IF IT'S ACTUALLY DIGITAL FUNDING FOR IT BUT WE HAVE HAD A JUNIOR PHYSICIAN SCIENTIST EVERY YEAR ON OUR WELLSTONE AND I THINK THAT'S BEEN A SUCCESSFUL AVENUE FOR DEVELOPMENT. BUT PROBABLY WITH FUNDING. (OFF MIC) >> RIGHT. WHAT COULD THE INSTITUTIONS DO, SO THERE'S AN AWFUL LOT OF EM IFSIS ON FUNDING -- EMPHASIS ON FUNDING CHAIRS AND ENDOW CHAIRS FOR PEOPLE TOWARDS THE END OF THEIR PRODUCTIVITY. AND I THINK ONE OF THE REASONS TO DO THAT IS BECAUSE THO EAR NOT BRINGING IN -- THEY'RE NOT BRINGING IN SALARY SUPPORT BUT UNIVERSITY IS NOT GOING TO LET THEM GO. THAT IS SO BACKWARDS THAT WE SHOULD BE DEVELOPING PHILANTHROPIC SUPPORT FOR OUR PROMISING YOUNG FACULTY, EVEN IF THAT'S ONLY TEMPORARY. YOU GET THE SUPPORTER ENDOWED CHAIR FOR THREE YEARS THEN IT GOES TO NEXT JUNIOR FACULTY. THAT'S ALL MY THOUGHTS. >> TO VALIDATE FURTHER IF WE MISINTERPRETED WHAT I WAS TRYING TO SAY, IS THE TRANSITION FROM K AWARD TO RO1, YOUR POINT ABOUT THE DIFFICULTY WITH REGARD TO CLINICAL RESEARCH, TAKE THOSE WORKING AT THE BENCH, KO 8 AWARDEES, I'M TALKING CLINICIAN PEOPLE WITH -- AND THESE VETERINARY SCIENTIST, THE YOU CAN IS SAYS IS CLOSE TO 50% WHO APPLY, WITH REGARD TO CLINICAL RESEARCH, THOSE WHO APPLY SUCCESS RATE IS ABOUT 25%. FROM SO A CLEAR DIFFERENCE, AND FROM YOUR IMPRESSION THAT TRANSITION BECOMES VERY, VERY DIFFICULT. MUCH MORE DIFFICULT FOR CLINICIAN INVESTIGATORS AND NINDS DEALS WITH IT DIFFERENT WAY, >> WE NOTICED THOSE BUT THOSE LISTED GO TO K 23s AND DON'T HAVE CLINICAL DATA TO GET RO1. SO GIVE THEM A KO 2 FOR FIVE YEARS BUT AFTER THREE YEARS THEY HAVE TO HAVE SUBMITTED RO1, BY THE FOURTH YEAR HAVE GOTTEN THE RO1 # SO IT'S MEANT TO EXTEND -- IT'S MEANT TO RECOGNIZE THE FACT THAT IT CAN TAKE LONGER TO GET CLINICAL DATA THAT ONE WOULD NEED TO GET INDEPENDENT RO1. ONE THING I WAS SURPRISED NEITHER OF YOU MENTIONED BECAUSE IT WAS SO OBVIOUS YOU DIDN'T THINK WORTH MENTIONING BUT I DIDN'T SEE MENTION OF LAUNDRY PAYMENT IN THERE, THAT'S ANOTHER PROGRAM WE PUT A FAIR BIT OF MONEY INTO. >> BUT I WAS CURIOUS WHETHER YOU HAD SEEN THAT MAKING SIGNIFICANT CONTRIBUTION PEOPLE DECIDING TO STAY OR YOU DIDN'T MENTION DEBT LOAD AS REASON WHY PEOPLE DROPPED OUT. JIM. >> SO I COULDN'T AGREE MORE WITH THE COMMENT ABOUT LOAN REPAYMENT PROGRAM, WE DID A BEING ANALYSIS OF THIS IN NHLBI BECAUSE WE FUND A BIT. ONE THING THAT WAS STRIKING AND OUR COUNCIL WAS IMPRESSED BY THIS IS, IS THAT THOSE THAT GET LOAN REPAYMENT PROGRAM HAVE HIGHER SUCCESS RATE OF K AND STEVE MENTIONED THEIR SUCCESS OF GOING TON GET THEIR FIRST R IS HIGHER. IF YOU DO A COMPARISON OF THOSE WHO DON'T HAVE LOAN REPAYMENT PROGRAMS, THOSE WHO APPLY AND DIDN'T GET THE LOAN REPAYMENT -- DIDN'T GET AN APPROXIMATE WARED YOU CAN SEE SEPARATION OF THOSE SUCCESSFUL IN THAT DOMAIN. THAT PROMMED OUR INSTITUTE TO TRY HARD TO LINK K WITH LRP TO TRY TO MAKE SURE THAT WE SET THEM UP FOR SUCCESS IN TERMS OF FUTURE SUCCESS GETTING AN RO1. >> AND SUCCESS OF THE LOAN REPAYMENT, AT LEAST IN OUR INSTITUTE IS HIGH. KATHRYN COMMENT ON THIS? >> NO, I DON HAVE A LOT OF INFORMATION OR EXPERIENCE WITH THAT. I'LL USE THAT AS A CARE ROOT. -- CARROT. >> BIG CARROT. IT'S $35,000 A YEAR FOR THE FIRST AWARD. AND TAXES PAID THEN RENEWABLE FOR ANOTHER $35,000 PER YEAR FOR THE NEXT TWO YEARS SO IT ADDS TO $140,000, I HAVEN'T READ THE PAPER TODAY OR LOOKED AT MY COMPUTER TOO MUCH, BUT IF THE EXCUSER ACT GOES THROUGH, THAT INCREASED TO $50,000 A YEAR TO GO WITH THE INCREASED LOAN PEOPLE HAVE FROM PROFESSIONAL SCHOOLS. YES. VALERIE. >> I WANTED TO FOLLOW-UP ON YOUR POINT ABOUT THE CLINICAL RESEARCHERS, NOT THE BENCH PEOPLE, THOSE WHO ARE TRAINING IN CLINICAL RESEARCH METHODOLOGIES AND THINGS LIKE THAT WHO ARE CLINICAL TRIALSISTS GOING FORWARD. THERE'S A SHORTAGE OF THOSE. MDA HAS FOR A NUMBER OF YEARS FUNDING CLINICAL RESEARCH TRAINING GRANTS. FROM HIGHER IN A MOUND THAN AAN BUT WE ONLY GET MAYBE FIVE A YEAR. SO WE PARTNERED THIS YEAR WITH AAN FOR THEIR 2017 AWARDS BUT NOT CERTAIN THE NUMBERS ARE THAT MUCH HIGHER. FROM SO THERE'S AN ISSUE YOU TALK ABOUT THE NEED TO RECRUIT MORE YOUNG PEOPLE INTO THE FIELD. BUT A NUMBER OF CLINICS ARE GETTING LONG IN THE TOOTH AND WE NEED THAT NEXT GENERATION. >> SO KATHRYN, THANKS FOR THE NICE PRESENTATION. SO WHEN YOU TALK ABOUT DROP OUT, YOU MEAN LEAVING RESEARCH AND DOING EXCLUSIVELY CLINICAL BASE WORK, RIGHT? >> YEAH. AND MANY MANY PEOPLE ARE ALSO LEAVING ACADEMIA. >> OKAY. I'M WONDERING, THERE'S STILL MAYBE A LOT OF VALUE IN THE PEOPLE THAT GO FOR CLINICAL PRACTICE OR MAY ALSO BE INVOLVED IN CLINICAL RESEARCH BUT JUST NOT LEADING CLINICAL RESEARCH. THEY DON'T HOLD -- THEY'RE NOT PIs ON THE GRANTS THAT FUND THE RESEARCH BUT THEY'RE STILL INVOLVED IN MULTI-SITE STUDIES AND THAT SORT OF THING. SO AS COMPARED TO AN ACADEMIC Ph.D. DOES NOT HAVE CLINICAL RESPONSIBILITY TO FALL BACK ON SO WHEN YOU TALK DROP OUT THERE, IT MAY MEAN LOSING TO THE DYSTROPHY FIELD AND OTHER STUFF WE WANT TO SEE UPHELD. WHAT OVER ROLES DO PEOPLE PLAY WHEN NO LONGER ON THE TRACK TO BE PIs IN GRANTS? THERE ARE SOME PEOPLE 100% CLINICAL IN ACADEMIC MEDICAL CENTERS. AND SO THEY MAY SEE PATIENTS WITH MUSCULAR DYSTROPHY AND THAT'S VERY VALUABLE THEY HAVE HAD THIS EXPOSURE THOUGH THEY'RE NOT DOING RESEARCH. THEN SOME DROP OUT TO BE IN GROUP OR SOLO PRACTICE. FOR NEUROLOGY, MOST PEOPLE ARE TRAINED IN EMG SO THAT REALLY IS A LESS LUCRATIVE THAN USED TO BE BUT A WAY PEOPLE CAN SUPPORT THEMSELVES. >> THIS MAYBE ANECDOTAL BUT I CAN RATTLE OFF NAMES. NUMBER OF NEUROMUSCULAR NEUROLOGISTS HAVE GONE TO COMPANIES TO SUPPORT TRIALS IN THAT SPACE THE LAST COUPLE OF YEARS. MAYBE ANECDOTAL BUT I CAN GIVE YOU A GOOD LIST OF NAMES. >> THOSE ARE SUCCESSES, THOSE ARE SUCCESSES. BUT WE DO AS YOU'LL HEAR FROM TOM, WE'RE CONCERNED ABOUT SUPPORTING THIS RESEARCH THROUGH THE NIH AS WELL. YOU NEED WELL TRAINED PEOPLE. TOM IS PROGRAM DIRECTOR AT NIMS WHO WILL PRESENT ANALYSIS OF GRANT APPLICATIONS AND THE OUTCOMES OF NEW INVESTIGATOR AWARDS IN MUSCULAR DYSTROPHIES. >> THANKS, DR. KATZ, THANKS TO A LOT OF PEOPLE FOR THIS ANALYSIS, GLENN NUCKOLLS, KRISTIN TROWBERG AND AMANDA VOICE AT NIAMS. PUTTING TOGETHER THIS ANALYSIS, I HAD THREE MAIN GOALS THAT I WANTED TO ADDRESS. THIS WAS ALSO BASED ON EARLY CONVERSATIONS WE HAD WITH DR. WINGER AND DR. CAMPBELL, WHEN DEVELOPING THIS SESSION. SO THE FIRST IS TO LOOK AT ESSENTIALLY WHAT ARE THE SUCCESS RATES OF MUSCULAR DYSTROPHY NEW INVESTIGATORS AND SO WE'RE ON THE SAME PAGE, I USE THE NIH DEFINITION FOR NEW INVESTIGATOR SO THIS IS AN INDIVIDUAL WHO NOT RECEIVED SUBSTANTIAL NIH INDEPENDENT RESEARCH SUPPORT. SECOND QUESTION WAS LOOKING AT RETENTION OF NEW INVESTIGATORS IN NIH AND BROADER MUSCULAR DYSTROPHY RESEARCH POOL. THIRDLY PROVIDING CONTEXT FOR PART TWO OF THE PRESENTATION WHICH IS SESSION PRESENTED REALLY FEATURING PERSPECTIVES OF PROVIDING QUALITATIVE AND QUANTITATIVE INFORMATION TO GET A FULL PICTURE OF WHAT THE WORK FORCE PIPELINE IS LIKE. AT THE LAST MDCC MEETING GLENN PRESENTED THIS DATA LOOKING AT THE PERCENTAGE OF COMPETING RO1 AWARDEES WHO ARE NEW INVESTIGATORS. SO IN GREEN WE'RE LOOKING AT AWARDEES IN MUSCULAR DYSTROPHIES AND COMPARED TO PURPLE ACROSS NIH. THERE WAS A CONCERN IN THAT THERE IS A DOWNWARD TREND IN SENSE OF COMPETING RO 1s GOING TO NEW INVESTIGATORS IN MUSCULAR DYSTROPHIES. THE CAVEAT TO THIS IS THAT IN GENERAL THERE ARE -- THERE'S ONLY A SMALL NUMBER OF RO1 AWARDS GOING TO NEW INVESTIGATORS. SO IN 2015 WITH PARTICULARLY LOW YEAR AND I WANT THE DYE INTO THIS TO ASSESS IS IT AN OUTLIAR OF A YEAR AND TRY TO MORE FULLY UNDERSTAND WHAT'S GOING ON. BUT BEFORE I DO THAT, I THINK IT'S HELPFUL TO LOOK AT THE BROADER CONTEXT OF THE ENTIRE NIH RO1 MUSCULAR DYSTROPHY PORTFOLIO. SO TALKING COMPETEK AWARDS, THAT LAST ONE WAS TALKING ABOUT, WE'RE ONLY TALKING ABOUT A SMALL PERCENTAGE OF THE ENTIRE NIH POOL SO WHAT I HAVE HERE IN BLUE AT THE BOTTOM ARE PERCENT PORTFOLIO GOING TO COMPETING NEW INVESTIGATOR AWARDS AND IN RED IS PERCENT OF PORTFOLIO THAT'S GOING TO ESTABLISH PIs ON THEIR COMPETING AWARDS. AND THESE COMPETING AWARDS WHEN THEY'RE UP FOR PEER REVIEW AND FUNDING DECISIONS ARE MADE. BUT THE REMAINING 70 TO 80% OF THE PORTFOLIO GOES TO NON-COMPETING AWARDS, SO YEARS # THROUGH 5 OF STANDARD RO1 AWARD. SO I'M STRESSING LOOKING AT SMALL NUMBERS, IN PART BECAUSE WE'RE ONLY LOOKING AT THIS ESSENTIALLY SMALL PORTION OF THE PORTFOLIO HERE, THOSE AWARDS ACTIVELY UNDERGOING PEER REVIEW. FROM WHENEVER WE DO ANALYSIS LIKE THIS, I THINK ONE OF THE FIRST THINGS TO DO THAT'S HELPFUL IS TO LOOK AT THE APPLICATION TRENDS BECAUSE ADS DR. KATZ MENTIONED DEPENDENT ON THE APPLICATIONS WE RECEIVE SO HELPFUL TO KNOW WHAT ARE THE RELATIVE TRENDS IN THE PREVIOUS YEARS. SO FIRST I LOOKED AT NEW RO1 APPLICATIONS FROM ESTABLISHED PI, THE SOLID BLUE LINE COMPARED TO NEW RO1 APPLICATIONS FROM NEW INVESTIGATORS. THERE'S CERTAINLY A SLIGHT INCREASE LOOKING AT 2008 THROUGH 2015 IN RO1 APPLICATIONS. SO THERE'S NOT NECESSARILY A DOWNWARD TREND. BUT ALSO LOOK AT R21 APPLICATIONS SO THESE ARE SMALLER AWARDS, SHORTER PERIOD OF TIME AND THE INTENT HERE IS TO HELP INVESTIGATORS TEST OUT NEW HIGH RISK IDEA OR DEVELOP A NEW MODEL BUT INTENT AND DESIGN IS NOT TO HELP NEW INVESTIGATOR ESTABLISH A NEW LAB SO THESE ARE RELATIVELY STABLE TREND OF APPLICATIONS BETWEEN MULTI-NEW INVESTIGATORS COMPARED TO ESTABLISHED PI ET CETERA BUT IT'S INTERESTING THAT THESE LINES TEND TO OVERLAP. AND I THINK IT'S IMPORTANT TO NOTE NIH HAS SEVERAL POLICIES, TO TRY TO HELP OUT NEW INVESTIGATORS. ONE DURING REVIEW NEW INVESTIGATOR APPLICATIONS ARE GROUPED TOGETHER. SO THAT REVIEWERS FOCUS ON THE FACT OF NEW INVESTIGATORS COMPARED TO PEOPLE WHO HAVE BEEN ESTABLISHED IN THE FIELD. FROM MOST INSTITUTES HAVE DIFFERENT POLICIES TO HELP NEW INVESTIGATOR APPLICATIONS A BUMP ON THE PAY LINE SOMETIMES 5% ABOVE STANDARD PAY LINE, TRYING TO GET? INVESTIGATORS SUCCESS RATES AND ESTABLISHED INVESTIGATORS, BUT IT DOESN'T A APPLY R21, IT'S RO1 AND THIS IS THE TYPE OF AWARD YOU CAN BUILD A CAREER OFF OF. SEW NEXT QUESTION, WE HAVE A TREND OF APPLICATIONS BUT WHAT ARE THE OUTCOMES ON THOSE APPLICATION? SO FOR THIS, IT IS HELPFUL TO DESCRIBE THE DATA SET I USED HERE. SO ALL APPLICATIONS THAT COME TOP THE NIH ARE TEXT MINE AND CODED, BY A SYSTEM CALLED THE RESEARCH CONDITION AND DISEASE CATEGORIZATION SYSTEM OR RCDC. IF YOU LOOK AT SPENDING ON NIH SUPPORTER, IT'S SYSTEMS DRIVE FROM DATA CODED USING THIS SYSTEM. SO FOR MY ANALYSIS, I DOWNLOADED ALL APPLICATIONS CODED AS MUSCULAR DYSTROPHY BY RCDC SYSTEM. AND IT WAS IMPORTANT TO KNOW IT'S ONLY A SPECIFIC TIME WINDOW HERE, FISCAL YEARS 2008 TO 15. THAT'S BECAUSE MUSCULAR DYSTROPHY STARTED IN 2008, TECHNICALLY BUDGET DATA IS CLOSED UP THROUGH FISCAL YEAR 15. TAKES THE NEXT PRESIDENT BUDGET THE NEXT FISCAL YEAR FOR THAT YEAR TO FINALIZE SO WE'RE GETTING CLOSE ON 16 DATA BUT NOT TECHNICALLY CLOSED THOUGH I WILL SHOW A GLIMPSE OF DATA, BUT NOT COMPLETELY FINALIZED. SO ONCE I HAD THIS INFORMATION DOWNLOADED, THE NEXT QUESTION IS LOOKING AT HOW WE ANALYZE THE OUTCOMES OF THESE APPLICATIONS. NIH HAS SEVERAL METRICS THAT IT USES TO LOOK AT THIS. BUT SUCCESS RATE IS ONE THAT'S THE MOST COMMONLY USED AND COMMONLY DISCUSSED AND YOU CAN THINK OF IT IS WHAT'S THE LIKELIHOOD OF PROJECT FUNDED IN ANY GIVEN FISCAL YEAR. NIH HAS POLICY THAT OVERALL THE ACROSS THE NIH THE GOAL IS TO HAVE NEW INVESTIGATORS SUCCESS RATES COMPARABLE TO THOSE NEW APPLICATIONS OR ESTABLISHED INVESTIGATORS. WE USE POLICIES TO TRY TO MEET THAT GOAL. HOW SUCCESS RATES ISCALULATED DOWN HERE, ESSENTIALLY NUMBER OF AWARDS IN A FISCAL YEAR OVER APPLICATIONS REVIEWED, AND THE NOTE THAT YOU ACTUALLY ARE EXCLUDING RESUBMISSION OCCURRING IN THE SAME FISCAL YEAR AND MULTIPLYING THIS BY 100 TO GET THE PERCENT. SO I DID THAT ANALYSIS. ONE THING I WANTED TO PRESENT FIST BEFORE SHOWING THAT DATA IS THAT IF WE WANT TO COMPARE NEW INVESTIGATORS TO NIH INVESTIGATORS, ACROSS ENTIRE AGENCY, THE SCALES ARE DRAMATICALLY DIFFERENT. MUSCULAR DYSTROPHY, IF WE LOOK AT NUMBER OF NEW INVESTIGATOR AWARDS, WE'RE TALKING BETWEEN ONE IN FIVE COMPARED TO NIH NUMBERS, 1,000, 1500, WHAT I WANT TO STRESS IS THAT WITH THESE SMALL NUMBERS, IT BRINGS IN VARIABILITY IN THE DATA. AND YOU CAN IMAGINE A FEW MORE AWARDS DRAMATICALLY AFFECT MAGNITUDE OF TRENDS SO I THINK IT'S IMPORTANT TO KEEP THAT IN MIND. SO LOOKING AT SUCCESS RATE ACROSS THE TIME PERIOD I DISCUSS 2008 TO 2015, WHAT I APPLAUDED IN THE DASH LINE HERE IS SUCCESS RATE OF MUSCULAR DYSTROPHY NEW INVESTIGATORS AND WHEN YOU CAN SEE IS REALLY A LOT OF VARIABLE, THERE'S SOME YEARS CLOSE TO NIH NEW INVESTIGATORS WHICH IS THE DOTTED RED LINE, OTHER YEARS IT'S LOWER. MUSCULAR DYSTROPHY ESTABLISHED INVESTIGATORS ACTUALLY IN CERTAIN YEARS SEEMED TO DO BETTER THAN EVEN IF NIH OVERALL ESTABLISHED INVESTIGATORS. JUST INTERESTING TO NOTE IF YOU LOOK AT 2016 DATA WHICH AGAIN IS FINALIZED BUT THESE ARE AWARDS UNRECORDED THAT HAVE BEEN ISSUED, IT'S THE BEST YEAR IN ITS ENTIRE PERIOD FOR NEW INVESTIGATORS AND ESTABLISHED INVESTIGATORS. I POINT TOUT STRESS THAT BECAUSE OF THE SMALL NUMBERS THERE'S A LOT OF NOISE AND VARIATION IN THIS SYSTEM. BUT IF YOU DO TAKE THE DATA FROM 2008 TO 2015, COMBINE AND AVERAGE THIS, NEW INVESTIGATORS SEEM TO DO A LITTLE MORE POORLY COMPARED TO ESTABLISHED INVESTIGATORS WHO ACTUALLY APPEAR TO DO AS WELL IF NOT BETTER THAN ALL NIH ESTABLISHED INVESTIGATORS. TO TRY TO UNDERSTAND THAT MORE, I WANT TO DIVE DEEPER AND LOOK AT HOW DO THE SCORES ON MUSCULAR DYSTROPHY NEW INVESTIGATOR APPLICATIONS COMPARE TO ESTABLISHED MUSCULAR DYSTROPHY INVESTIGATORS. TO GIVE A CRASH COURSE ON NIH PEER REVIEW, APPLICATIONS ARE REVIEWED BY A NUMBER OF STUDY SECTIONS, MANY IN A LOT OF CASES. SCORES NORMALIZE BY PERCENT OF APPLICATIONS AGAINST APPLICATION PREVIOUSLY REVIEWED IN THAT REVIEW GROUP TO ESSENTIALLY YOU CAN GET RANK BY PERCENTILE. WHEN I LOOK AT THE PERCENTILE SCORES OF MUSCULAR DYSTROPHY APPLICATIONS, WHAT I FOUND IS THAT NEW INVESTIGATOR AND ESTABLISHED INVESTIGATOR RO1s DISCUSS AND SCORED PERCENTILE WE EQUIVALENT RATES BUT LOOK AT A HISTOGRAM SHOWING THE DISTRIBUTION OF PERCENTILE SCORES, SO I HAVE A BINNED IN 5 PERCENTILE INCREMENTS THAT'S WHAT THE X AXIS AND Y AXIS AND NUMBER OF APPLICATIONS THAT FALL WITHIN THAT CERTAIN BIN YOU CAN SEE THEY'RE TWO DIFFERENT PATTERNS GOING ON FOR ESTABLISHED INVESTIGATORS VERSUS NEW INVESTIGATORS. ESTABLISHED INVESTIGATORS TEND TO BE SKEWED TOWARDS GOOD SCORING APPLICATIONS THAT PROBABLY FALL WITHIN THE FUNDING RANGE OF MOST INSTITUTES. BUT IT'S IMPORTANT TO NOTE THAT I HAVE A GRADIANT HERE THAT DIFFERENT SUITS HAVE DIFFERENT PAY LINES BUT IN GENERAL ROUGHLY WHERE THE RANGE IS TO BE. LOOK AT NEW INVESTIGATORS THE DISTRIBUTION IS SKEWED TOWARDS LOWER SCORING APPLICATIONS. AND IN A LOT OF CASES, FALLING OUTSIDE THAT NEW INVESTIGATOR BUMP THAT ALLOW INSTITUTES -- THAT USE, AGAIN, TO TRY TO HELP NEW INVESTIGATORS, AND THIS CAN ALSO BE SEEN IF YOU LOOK AT AVERAGE PERCENTILE SCORE, NEW INVESTIGATORS THE AVERAGE IS 33 ACROSS THE TIME PERIOD, ESTABLISHED INVESTIGATORS IS 25th PERCENTILE. SO THE NEXT QUESTION, FOR THOSE INVESTIGATORS THAT DO RECEIVE AN AWARD, WHAT HAPPENS ONCE THEY'RE FUNDED IN AND TRYING TO GET RETENTION RATES IN THE WORK FORCE ESSENTIALLY. SO AGAIN, ANOTHER LIMITATION OF ANALYSIS IS I CAN ONLY GO BACK TO 2008 AND IF WE THINK ABOUT FIVE YEAR AWARDS, A LOT OF TIMES EXTENDED WITH NO COST EXTENSION, AMOUNT OF TIME WE'RE WORKING ON THERE, THEY'RE LIKELY NOT A SIGNIFICANT AMOUNT OF TURN OVER SO OUT OF 22 NEW INVESTIGATOR RO1s AWARDED WITHIN THAT TIME PERIOD, 2008 TO 2015, THERE'S ONLY NINE THAT HAVE ENDED OR BECOME INACTIVE AND IN THE SENSE BE ELIGIBLE TO TRY TO RENEW THAT APPLICATION OR RENOW THAT ORG. SO OF THOSE NINE THAT HAVE ENDED OR INACTIVE, FIVE HAVE SUBMITTED RENEWAL ATTEMPTS TO DATE, BUT NONE HAVE BEEN FUNDED AT PRESENT ANYWAY. ANOTHER QUESTION TO GET AT, GETTING INTO WHAT DR. CAMPBELL BROUGHT UP HOW IMPORTANT IT IS FOR NEW INVESTIGATORS TO GET A SECOND RO1 AND THAT CAN INFLUENCE THEIR CAREER TRAJECTORY, I WANTED TO LOOK AT OF THOSE PI WHERE THEY HAD AN RO1 BUT NOW INACTIVE, HOW MANY RECEIVED A SECOND RO1 AT SOME POINT IN THE TIME FRAME. SO OF THE NINE, THREE DID. SO 33%. TWO-THIRDS WERE ON A MUSCULAR DYSTROPHY RELATED TOPIC. THEN TAKE IT A STEP BACK AND LOOKING AT THOUGH INVESTIGATORS -- THOSE INVESTIGATORS AWARD IS LAPSED HOW MANY ARE STILL FUNDED TO DO MUSCULAR DYSTROPHY RESEARCH? REGARDLESS OF SOURCE. SO 44% ARE CURRENTLY FUNDED TO DO MUSCULAR DYSTROPHY RESEARCH. HALF ARE FUNDED SOLELY THROUGH NIH SUPPORT WHETHER RO1 R # 1 OR INVESTIGATOR ON A CORE OR CENTER GRANT, A QUARTER ARE SOLELY SUPPORTED FROM ANOTHER MDCC MEMBER, TO GET THIS DATA I USED THE PORTFOLIO ANALYSIS THAT MDCC WORK DONE FOR FY 15 AND THAT CAN BE HELPFUL FOR GOING FORWARD AS WELL. AND TRYING TO GET A SENSE OF ENTIRE SPECTRUM OF FUNDING FOR MUSCULAR DYSTROPHY RESEARCH. THEN TO CLOSE UP, THERE WAS ANOTHER QUARTER BUT AGAIN ONLY ONE PERSON. HAD A COMBINATION OF NIH AND OTHER MDCC MEMBER SUPPORT. THIS BE TO TRY TO CLOSE THE LOOP, HOW MANY SLAYTORS THAT DON'T HAVE ACTIVE MUSCULAR DYSTROPHY FUNDING ARE FUNDED BUT IN OTHER AREAS OF RESEARCH? SO THAT'S TWO OF NINE, 22 PEST. IF WE COMBINE -- 22%. IF WE COMBINE WITH SHARE PREVIOUS BULLET, FIVE OF NINE OR 56% CURRENTLY HAVE ACTIVE NIH RESEARCH SUPPORT AND THE POINT I'M TRYING TO MAKE HERE IS GETTING THAT JUST OVERALL RETENTION IN THE NIH FUNDING POOL. AFTER THAT FIRST RO1 TENDS TO BE A RELATIVELY LARGE DROP OFF IN PERCENT OF INVESTIGATORS STILL SUPPORTED. AND I CAN GIVE AN EXAMPLE HERE, THIS IS DATA FROM THE OFFICE OF EXTERNAL RESEARCH THEY PUBLISHED IN ONE OF THEIR BLOGS. IT'S LOOKING AT ON THE X AXIS YEARS SINCE THE FIRST RO1 WAS AWARDED. I HAVE THE DOTTED LINE HERE AT FIVE, WHICH WOULD BE ROUGHLY WHEN THE FIRST RO1 MAY HAVE EXPIRED. ON THE X AXIS WE LOOK AT PERCENT OF AWARDEES WHO CONTINUE TO RECEIVE IN GENERAL SOME SUBSTANTIAL RESEARCH SUPPORT FROM THE NIH. AND THEY LOOK AT THREE DIFFERENT COHORTS HERE. SO THIS BLUE LINE IS FROM A 1989 COHORT, GREEN IS FROM A 2003 COHORT AND RED FROM A 1997 COHORT. AND WHAT I WANTED TO DRAW YOUR ATTENTION TO IS THE LARGEST DROP HERE IN TERMS OF RETENTION POOL IS ROUGHLY AROUND THAT FIVE YEAR POINT WHEN FIRST RO1 EXPIRES, SOME CASES AROUND 50 TO 60%. SO IN THAT SENSE, MUSCULAR DYSTROPHY NIH INVESTIGATORS, ARE ABOUT ROUGHLY EQUIVALENT TO THE ENTIRE NIH POOL BUT IT'S AN AREA THAT THE ENTIRE NIH IS INTERESTED IN TRYING TO FOCUS ON AND SEE WHAT WE CAN DO TO SUPPORT IN THEIR CAREER DEVELOPMENT SO THE MAIN TAKE HOME POINT BEFORE TURNING TO GLENN IS THE SUCCESS RATE OF MUSCULAR DYSTROPHY NEW INVESTIGATORS OBTAINING THAT FIRST NIH RO1 REALLY VARIES FROM YEAR-TO-YEAR, IT'S ESPECIALLY DIFFICULT TO DRAW CONCLUSIONS BASED ON THE SMALL NUMBERS WE HAVE. BUT THERE IS A TREND THAT TENDS TO BE LESS SUCCESSFUL THAN ESTABLISHED MUSCULAR DYSTROPHY INVESTIGATORS. AT LEAST OVER THAT FISCALLIER PERIOD 2008 TO 2015. BUT IT'S WORTH POINTING OUT ADS WELL, ESTABLISHED INVESTIGATORS HOWEVER, DO IT WELL OR BETTER THAN AN ENTIRE NIH COMPARATOR POOL. LOOKING AT RETENTION, THIS WAS ANOTHER AREA OF OPPORTUNITY FOR THE ENTIRE MUSCULAR DYSTROPHY RESEARCH COMMUNITY. IT IS IMPORTANT TO NOTE THIS IS CHALLENGING NOT JUST MUSCULAR DYSTROPHY BUT ACROSS THE NIH. ANOTHER POINT REALLY IS MUSCULAR DYSTROPHY RESEARCHERS CAN MAINTAIN FUNDING FOR PROGRAMS FROM A RANGE OF SOURCES, MANY PARTIES A T THIS TABLE, KEEPING THAT IN MIND AND ANALYZING THAT DATA IS HELPFUL TRYING TO GET A FULL PICTURE OF THE WORK FORCE. THEN FINALLY I WANTED TO HIGHLIGHT LIMITATIONS OF THIS ANALYSIS. AS STRESSING SMALL NUMBER INVESTIGATORS AWARDS CONTRIBUTES TO SIGNIFICANT VARIABILITY OBSERVED IN THE OUTCOMES. AND NIH DATA IS LIMITED TO THAT CODED BY RCDC SYSTEM AND ALSO LIMITED TO THOSE MDCC MEMBERS THAT PARTICIPATED IN THE PORTFOLIO ANALYSIS, DATA CALL FROM LAST YEAR. AND WE APPRECIATE YOUR EFFORTS ON THAT. I THINK IT CAN BE EVEN MORE HELPFUL GOING FORWARD. SO HOPEFULLY THIS HELPS SET UP A BASELINE ANYWAY, TO THE NEXT PRESENTATION WHICH IS PERSPECTIVES FROM GRANTEES AND APPLICANTS THAT GLENN WILL BE PRESENTING. [APPLAUSE] >> THANKS VERY MUCH, TOM. ANY YES, SIR >> >> THAT'S THE REASON FOR THIS DISCUSSION WAS THAT THAT WAS THE DATA THAT GLENN SHOWED LAST TIME. >> WHAT ABOUT THE OTHER AREAS? DO YOU HAVE THE DATA FOR OTHER DISEASES? LIKE FOR CF OR OTHER AREAS? >> WE DISCUSSED THIS A LOT ABOUT WHAT IS APPROPRIATE COMPARATOR GROUP. AND I THINK IF YOU LOOK AT ANOTHER DISEASE THE IDEAL COMPARATOR GROUP IS DISEASE OF SIMILAR PREVALENCE, A DISEASE THAT IS SIMILAR STAGE UNDERSTANDING OF PATHOGENESIS, WORK FORCE SIDE, POPULATION SIDE AND IF YOU LOOK AT THE VARIABLES THAT IT IS CHALLENGING TO FIND A COMPARATOR, WHY WE COMPARE THE NIH OVER BUT THAT'S NOT A COMPARATOR EITHER. WE STRUGGLE WITH CAVEATS TO ANY OTHER SPECIFIC COMPARATOR. (OFF MIC) >> HOW MANY APPLICANTS, TWO OR THREE AWARDS, HOW MANY APPLICANTS DO YOU HAVE? >> THAT'S WHAT SUCCESS RATES ARE, >> TOTAL NUMBER. >> DEPENDS IF YOU'RE TALKING ABOUT WHICH POOL, NEW INVESTIGATORS, IN THE 20s AND 30s. >> 20 OR 30 APPLICANTS FUNDING -- >> EACH FISCAL YEAR. >> OKAY. REALLY SEEMS LIKE IF THERE WAS A PROGRAM CF FOUNDATION HAD A PROGRAM WHERE GRANTS THAT DIDN'T GET FUNDED YOU COULD SUBMIT THE GRANTS AND THE PINK SHEETS TO THE FOUNDATION AND THEY WOULD FUND THE NEXT TWO OR THREE GRANTS FOR TWO YEARS, SOMETHING A PERSON WOULDN'T HAVE TO SUBMIT NEW GRANTS JUST GET THAT FUNDED. SEEMS LIKE WE HAD A PROGRAM LIKE THAT FROM NDA OR OTHER GROUPS, THAT COULD REALLY HELP, TRIPLE THE NUMBER OF GRANTS EASILY. >> THERE IS A PROGRAM PILOT PROGRAM LIKE THAT, ONLINE PARTNERSHIP, PTMD IS ONE OF THE PLAYERS I WOULD ENCOURAGE APPLICANTS TO LOOK INTO THAT, IT'S SOMETHING THAT I CAN'T JUST AUTOMATICALLY SUBMIT APPLICATION, THAT'S CONFIDENTIAL INFORMATION BUT MAKE THEM AWARE OF THAT PROGRAM AND THAT'S A BIG HOPE THAT I HAVE TOO THAT WE CAN HELP SUPPORT THOSE APPLICATIONS THAT JUST MISS THE PAY LINE WITHOUT REQUIRING NEW SUBMISSION NEW REVIEW. >> AND I CAN SAY THAT WE AS AN INSTITUTE HAVE HAD AGREEMENTS WITH OTHER ORGANIZATIONS THEY WANT TO SEE THOSE APPLICATIONS AND WHAT WE DO. FOR EXAMPLE RESEARCH FOUNDATION WITH A NATIONAL PSORIASIS FOUNDATION, THEY WANT TO SEE FOUNDATIONS INTERESTED IN FUNDING THEM WE WOULD CHECK WITH THE INVESTIGATOR AND JUST TELL THE INVESTIGATOR, THEY COULD IF THEY WANT, SEND THE APPLICATION ON TO ANOTHER ORGANIZATION. THIS OTHER, WHAT IS IT -- >> ON PAR. >> ON PAR. THE ON PAR ORGANIZATION ALMOST AUTO MACK. THE PARENT PROJECT CAN GO INTO THIS DATABASE AND LOOK AT APPLICATIONS THAT ARE OF RELEVANCE. >> THERE IS A FEE THE JOIN TA GROUP. AM I RIGHT, PATTED? >> WE'LL REPEAT IT, DAN. THIS IS THE ON PAR PROGRAM THAT PARENT PROJECT IS A PART OF. THIS IS REALLY FOR ORGANIZATIONS, FOR VOLUNTARY AND PROFESSIONAL ORGANIZATIONS WHO WANT TO PARTICIPATE IN THIS TYPE OF ACTIVITY. >> YEAH, I CAN -- WHILE THEY'RE GETTING THE MIC. >> I'M ABBY BRONSON FROM PPMD, WE WERE ONE OF THE ORIGINAL FUNDERS OR PARTNERS IN ON PAR. IN THE ORIGINAL COST WAS $25,000 PER YEAR BUT IT WAS AN ONGOING EVOLVING PROGRAM. SOME OF THE OTHER CHARTER MEMBERS WERE LARGER DISEASES AND IT WAS UP TO $25,000. THAT WAS BASED ON HOURLY VOLUME OF WORK BUT WITH RARE DISEASES THERE'S NOT MUCH COMING THROUGH SO THE PRICE HAS GONE DOWN AND WE'RE STILL WORKING -- I WORKED WITH TOM AND GLENN BOTH TRYING TO MAXIMIZE THE VALUE OF THIS PROGRAM. >> WE TALKED WITH ABBY A BIT, THERE'S LIMITATIONS TO THAT PROGRAM BECAUSE ESSENTIALLY WHAT THEY'RE DOING IS TAKING ENCOURAGING NIH APPLICANTS TO PUT THEIR APPLICATIONS IN TO THIS BIG POOL. THAT INCLUDES ALL NIH AND ON PAR IS USING KEY WORD SEARCHES TO TRY AND FISH OUT THE ONES THAT MIGHT BE USEFUL FOR A PARTICULAR ADVOCACY GROUP OR OTHER VOLUNTARY FOR FUNDING. AND WE WERE REALLY DON'T NEED TO DO THAT. WE KNOW WHICH ONES TO BE OF INTEREST OF PPMD OR OTHER ORGANIZATIONS, IT SEEMS MUCH EASIER THAT WE JUST TELL THE APPLICANTS TO CONTACT THE VOLUNTARY RATHER THAN HAVING THEM PAY $25,000 TO USE SOME KIND OF ALGORITHM TO FISH OUT ONES THEY KNOW WHERE THEY SHOULD GO. IT IS A SYSTEM, IT CERTAINLY WORKS BETTER IN MAYBE LARGER AREAS OF CANCER RESEARCH SO FORTH -- >> INFLAMMATORY DISEASES. >> EXACTLY. BUT IN RARE DISEASE AREAS WHERE IT'S VERY CLEAR WHAT THE VOLUNTARY WANTS TO FUND THEN DIRECT CONNECTION WITH THE PROGRAM DIRECTORS MAYBE IN THE LONG RUN MORE USEFUL. >> >> GO AHEAD DAN. >> JUST FOLLOWING WITH THAT, THE BE GREAT TO CAPITALIZE ON EXTRAORDINARY AUTHORITY OF PEER REVIEW. IN TERMS OF -- I HAVE A QUESTION FOR DR. CHEEVER. I TRY TO SENSE WHERE WHAT IS THE OVERALL, WHAT ARE YOU SEEING THE OVERALL NUMBER OF APPLICATIONS THAT ACTUALLY COME IN THE DOOR AND THOSE THAT ARE TRIAGED OR WHEN YOU SAY APPLICATIONS, AS YOU'RE SEEING TOTAL M.D. APPLICATIONS AT THE DOOR OR ARE YOU SEEING -- ARE YOU GETTING A SENSE OF THE SUPPLY SIDE IS GOING DOWN, OR RESPECT TO EACH TYPE CAN YOU GET A SENSE OF WHERE -- FSH, TEN APPLICATION AS YEAR TO ONE TWO, ANOTHER SUCCESS RATE, I DIDN'T QUITE CATCH THAT IN THE PRESENTATION. BUT I WAS CURIOUS TO KNOW WHETHER YOU SEE OVERALL DECLINE. >> I THINK I CAN ADDRESS THAT. GLENN JUST PULLED UP A SLIDE AND DATA OF APPLICATIONS SO THE SUPPLY SIDE IS GOING UP AT THE WORST STABLE FOR RO1 APPLICATIONS ANYWAY, THIS IS FOR ALL MUSCULAR DYSTROPHY. SO THIS IS CAPTURING ALL APPLICATIONS, NOT -- INCLUDING ONES THAT ARE TRIAGED BASED OFF CODED BY THAT RCDC SYSTEM. I THINK THIS TERMS OF SUPPLY SIDE, MORE APPLICATIONS COULD BE HELPFUL. IN TERMS OF TRYING TO INCREASE NUMBER OF AWARDS, ANYWAY. AND IN TERMS OF BREAKING DOWN SPECIFIC TIME OF DYSTROPHY, I DIDN'T DO THAT JUST BECAUSE I WANTED TO STAY BROAD FOR THE WHOLE AUDIENCE. BUT THAT'S SOMETHING WE CAN LOOK INTO GOING FURTHER. >> IS THAT DATA VAIL SOMEBODY >> THE AWARD IS AVAILABLE ON NIH REPORTER. >> (INDISCERNIBLE) MUSCULAR DYSTROPHY? >> I DIDN'T PRESENT THAT HERE ANYWAY. >> TO HELPFUL FOR US TO KNOW ADVOCACY ORGANIZATIONS AND KNOW HOW LOW THAT SUPPLY IS. GETTING ONE GRANT AND FUNDING 1 GRANT, CAN'T DO MUCH BETTER THAN THAT. >> YEAH. >> TOM IS ON THE TABLE. >> TOM AND I DID SOME OTHER ANALYSIS TO SEE HOW SCORING WAS GOING FOR NEW INVESTIGATORS, HE PRESENTED SOME OF IT. BUT FOR MUSCULAR DYSTROPHY, NEW INVESTIGATOR APPLICATIONS THERE'S SOME APPLICATION OVERALL SCORING IS REALLY QUITE GOOD AND PERHAPS BETTER THAN NEW INVESTIGATORS IN OTHER FIELDS. THE SUCCESS RATE IS STILL LOW. IT HAS TO DO WITH THE SHAPE OF THAT CURVE OF NUMBER OF SCORES PER RELATIVE TO THE PERCENTILE SCORES, OVERALL THEY'RE SCORED AND HAVE IT SHIFTEDDED A LITTLE BIT TO THE LEFT, BUT IN TERMS OF NARROW WINDOW REQUIRED FOR FUNDING, THEY'RE NOT HITTING THAT TARGET. SO WE TALK ABOUT ADDITIONAL WAYS WE CAN GIVE BETTER GUIDANCE TO NEW INVESTIGATORS. TO INCREASE LIKELIHOOD OF SUCCESS OF APPLICATIONS. WE HAVEN'T DONE IT YET BUT MAY TRY A DEEP DIVE OF SUMMARY STATEMENTS FOR MUSCULAR DYSTROPHY NEW INVESTIGATORS. TO SEE WHAT ARE THE COMMON THEMES WE MAKE SURE THEY'RE WORKING ON TO MAKE A DIFFERENCE IN THE PEER REVIEW. >> A LOT OF THE CURRENT REVIEWERS, ON STUDY SECTIONS ARE UNDER STRESS TO MAINTAIN FUNDING THEMSELVES COMPARED TO YEARS AGO WHEN STUDY SECTIONS HAD PEOPLE WITH TWO RO1s AND MORE SECURE SO COULD BE THAT'S REFLECTED, BEING TOUGHER ON THESE APPLICANTS. >> I THINK GLENN AND TOM, QUESTION ABOUT THIS. WITH CREATION OF SMITH IT'S FUNDED VIRTUALLY ALL THE MUSCULAR DYSTROPHY RO1s TO ONE STUDY SECTION. SO YOU HAVE POTENTIAL YES SEPARATING OUT NEW INVESTIGATORS BUFF POTENTIAL CONFLICTS THAT THEY KNOW ONLY WILL FUND THE FIRST FEW APPLICATIONS OUT OF THAT ONE STUDY SECTION. THOUGHT ABOUT THE IMPACT OF EVERYTHING FUNNELED TO ONE STUDY SECTION IN >> IF MUSCULAR DYSTROPHY WERE SEPARATED TO EIGHT STUDY SECTIONS THEY HAVE THE CHANCE OF BEING IN THE FUNDABLE RANGE OF EIGHT STUDY SECTIONS BUT IF THEY'RE ALL SMEP THEY'RE COMPETING AGAINST ONE ANOTHER AND YOU'RE LIMITED BY PERCENTILE SCORES THAT WILL BE WITHIN FUNDING RANGE. >> THERE IS ANOTHER SIDE TO THAT STORY. IF THEY'RE SPREAD OUT THERE'S NO CRITICAL MASS, THE POSSIBILITY IS THAT THE SPECIAL KNOWLEDGE REQUIRED TO REALLY REVIEW THESE APPLICATIONS APPROPRIATELY, WOULD BE LOST AND IT WOULD BE LOST ACROSS THE BOARD WITH ALL THOSE APPLICATIONS. SO WE CERTAINLY DON'T WANT THAT TO HAPPEN. >> THAT WAS THE ISSUE WE FACED AND WENT BEFORE INSTITUTE OF MEDICINE AND DONE SPECIAL WORKING GROUP. WHICH WOULD LEARN WHEN (INAUDIBLE) THAT HAD 4 INDIVIDUALS ON IT, IN THE EARLY DAYS ALL THE APPLICATIONS, THERE WASN'T ENOUGH SPECIAL EQUITIES AND SECTIONS SO A LOT OF GRANT DID NOT DO WELL AND WHEN THAT STUDY SECTION WAS FORMED THE (INAUDIBLE) GRANTS -- (INDISCERNIBLE) SO I CAN REMEMBER THE DAY WHEN IT WAS A LIABILITY NOT HAVE A STUDY SECTION. >> I THINK WE SHOULD MOVE ON. THANK YOU, DAN. I THINK WE SHOULD MOVE ON, GLENN WILL TALK ABOUT THE PERSPECTIVES OF NEW INVESTIGATORS. >> THANKS, STEVE. SO I WANT TO CONTINUE THIS TOPIC OF NEW INVESTIGATORS IN MUSCULAR DYSTROPHIES AND ADD THE PERSPECTIVE OF APPLICANTS AND GRANTEES AND I WANT TO ACKNOWLEDGE TOM AND HEATHER TOGETHER WE CONDUCTED PHONE INTERVIEWS WITH NIH RO1 NEW INVESTIGATOR APPLICANTS AND GRANTEES IN THE MUSCULAR DYSTROPHYs. AND I FOUND IT REALLY ENLIGHTENING, I HAVE BEEN A PROGRAM DIRECTOR FOR 12 YEARS AND I TALK WITH APPLICANTS AND GRANTEES ALL THE TIME, BUT USUALLY I'M TALKING A PARTICULAR PROJECT OR SUMMARY STATEMENT OR SOMETHING LIKE THIS AND I HAVEN'T HAD THE OPPORTUNITY TO TALK ABOUT WHAT IS ELSE IS GOING ON IN RESEARCH PROGRAMS AND OBSTACLES THEY'RE ENCOUNT EVERYTHING AND WHAT DO THEY SUGGEST FOR WAYS TO DEAL WITH IT. SO I THOUGHT IT WAS INTERESTING. SO THE PURPOSE OF THE ANALYSIS WAS BRING TO THE SESSION AN ADDITIONAL VIEWPOINT OF STAKEHOLDERS. WE HEARD FROM MENTORS, FUNDING ORGANIZATIONS AND I THINK IT'S WORTHWHILE TO CONSIDER THE PERSPECTIVES OF THE APPLICANTS AND THE GRANTEES. SO WE'RE INTERESTED IN WHAT THEY REPORT AS OBSTACLES TO FUNDING AND CAREER ADVANCE AND HOPEFULLY THIS WILL BE ANOTHER PIECE OF USEFUL INFORMATION THAT WILL CONTRIBUTE TO THE DEVELOPMENT OF A STRATEGY TO OVERCOME OBSTACLES AND PROMOTE SUCCESS OF MUSCULAR DYSTROPHY NEW INVESTIGATORS. THIS SHOW IT IS SAMPLE THAT WE SELECTED AND BY NO WAY SCIENTIFIC EXAMPLE. WE WANTED TO PICK PEOPLE APPLYING FOR THEIR FIRST RO1 BUT NOT SUCCESSFUL SO WE HAD THREE OF THOSE THAT ARE APPLICANTS, SOME ARE NEW INVESTIGATORS, ONE IS EARLY STAGE INVESTIGATOR, WHICH YOU MAY HAVE DEFINED, A PERSON WHO NOT HAD THEIR FIRST RO1 AND LESS THAN TEN YEARS BEYOND TERMINAL DEGREE. SO IT'S MORE PERHAPS YOUNGER NEW INVESTIGATOR. SO WE PICK PEOPLE DOING BASIC TRANSLATIONAL OR CLINICAL RESEARCH OR GENDER BALANCE AND RECORDED WHAT OTHER PREVIOUS THEN WE HAD TWO PEOPLE WHO ARE A COUPLE OF YEARS AFTER THEIR FIRST AWARD OF RO1 AND TRANSLATIONAL AND CLINICAL TO SEE HOW THINGS ARE GOING FOR THEM. AND COUPLE OF PEOPLE THAT HAD RO1s FOR LONGER PERIOD OF TIME AND EITHER AT THE TIME WHEN THEY SHOULD BE SUBMITTING FIRST RENEWAL APPLICATION OR PAST THE TIME SUBMITTING RENEWAL APPLICATION SO WE PICK THESE OUT OF THE RANK THAT WE HAVE SO THERE ARE LIMITS FOR PEOPLE WITH FEDERAL GOVERNMENT TO CONDUCT SURVEYS. SO WE CAN'T GO OVER NINE WITHOUT HAVING TO APPLY TO OFFICE OF MANAGEMENT BUDGET TO PROCESS THAT TAKES SIX MONTHS FOR APPROVAL. AND WE WANTED TO GO WITH A LITTLE SAMPLE AND SEE WHAT WE LEARNED FROM THIS WHICH IS QUITE INTERESTING AND USEFUL SO WE HAD A SET OF QUESTIONS DEVELOPED AND GOT KEVIN AND KATHRYN'S INPUT ON THOSE QUESTIONS TO GUIDE DISCUSSIONS WITH THE PEOPLE WE TALK TO SO QUESTIONS ABOUT RESOURCES NOT ONLY START UP PACKAGE BUT OTHER FOUNDATION SUPPORT, FUNDING RELATED STUFF BUT ALSO RESOURCES IN TERMS OF COLLABORATIVE NETWORKS THEY PARTICIPATE WITH AND WHAT WE HEARD THE EXPOSURE ISSUES SPIKING OPPORTUNITIES, COMMITTEE SERVICE OUTSIDE THEIR INSTITUTION, THAT SORT OF THING. WHO DO YOU GET MENTORING AND GUIDANCE FROM SO BOTH SCIENTIFIC AND NON-SCIENTIFIC TOPICS AND WE ASKED WHAT ARE THE ON STACKS THAT YOU FEEL TO GETTING FUNDED FROM NIH OR OTHER VOLUNTARY ORGANIZATIONS. ASIDE FROM INCREASING BUDGET RESEARCH, HOW COULD WE MAKE THEIR JOBS EASIER AND PERHAPS ATTRACT MORE INVESTIGATORS INTO THE FIELD. FREE FLOWING CONVERSATION SO WE TRY TO GET INFORMATION FROM EACH OF THEM ON THE TOPICS SO THE NEXT FEW SLIDES ARE SUMMARY OF WHAT THEY WERE SAYING IN DIFFERENT AREAS. WE SAW VARIABILITY IN STARTUP PACKAGES FROM ESSENTIALLY NOTHING INHERITING SOME EQUIPMENT TO OVER A MILLION DOLLARS PACKAGES SOME OF THEM MADE IT CLEAR THE UNIVERSITY SET STRICT TIME LIMITS ON THE USE OF THAT STARTUP PACKAGE. WHICH I THINK WAS INTENDED TO HAVE THEM GO AHEAD AND USE MONEY TO GET PROGRAMS STARTED RATHER THAN TRY AND TRAIL IT OUT OVER LONG PERIOD OF TIME. RESEARCH TIME PROTECTED FROM TEACHING OR CLINICAL RESPONSIBILITIES VARY QUITE A BIT FROM OOH 50% TO NEARLY # HUNDRED%, PEOPLE WHO ARE Ph.D.ES IN ACADEMIC INSTITUTIONS HAVE MORE PROTECTED RESEARCH TIME BECAUSE OTHER RESPONSIBILITIES WOULD BE TEACHING CLINICAL OR USUALLY IN THE 50 TO 75% PROTECTED TIME. SO ALL OF THE PEOPLE WE TALK TO REALLY APPRECIATED THE HAVING THE OPPORTUNITY TO APPLY TO PRIVATE FOUNDATIONS TO GET SUPPORT WHILE POST-DOCS OR AS INDEPENDENT INVESTIGATORS TO GET SUPPORT FOR PILOT PROJECTS, ALSO CTSA SUPPORT OTHER INSTITUTIONAL SUPPORT WAS IMPORTANT FOR MANY OF THEM, NIH CAREER DEVELOPMENT AWARDS, WE HEARD ABOUT K AWARDS MANY OF THEM SAID WERE VALUABLE SO KIND OF COMING TOGETHER FROM A VARIETY OF DIFFERENT SOURCES, AND I THINK THEY ALL FELT FORTUNATE TO BE IN THE MUSCULAR DYSTROPHY FIELD RATHER THAN SOME FIELD THAT DOESN'T HAVE PRIVATE FOUNDATION SUPPORT THAT THEY CAN APPLY TO. SO IN TERMS OF MENTORING, ALL SAID THEY NEED MENTORING ON NON-SCIENTIFIC TOPICS. THESE ARE ONES KEN AND KATHRYN COVERED, THINGS LIKE WHICH GRANTS TO APPLY FOR, WHAT TIME, WHICH JOURNAL TOES GO FOR BALANCING TIME INVESTMENT VERSUS JOURNAL PRESTIGE. HOW TO ESTABLISH AND MAINTAIN PRODUCTIVE COLLABORATIONS AND HOW TO INCREASE PROFESSIONAL EXPOSURE. PRETTY MUCH ALL PEOPLE WE TALKED TO, WERE PRETTY SATISFIED WITH THE MENTORING THAT THEY WERE GETTING FROM THEIR PEOPLE IN THEIR INSTITUTION, THEY FELT THAT THEY HAD PEOPLE TO TURN TO FOR THIS. BUT THEY ALSO WE HEARD SUGGESTIONS OF INTEREST IN SETTING UP SYSTEMS TO ALLOW FOR MORE REMOTE MENTORING. I WILL GET TO THAT IN LATER SLIDE TO TELL YOU MORE. KEVIN MENTIONED SOME INSTITUTIONS HAVE THESE FORMAL MENTORING PROGRAMS, THINGS LIKE INDIVIDUAL DEVELOPMENT PLANS AND GRANT APPLICATION PRE-PREVIEW COMMITTEES WHICH COULD BE VALUABLE OR HAVE DOWN SIDES, BUT I THINK FOR THE MOST PART PEOPLE THAT WE TALKED TO SAID IT'S REALLY JUST UP TO THE INDIVIDUAL INVESTIGATOR TO SEEK OUT THE MENTORING THEY NEED, IT'S UP TO THEM TO FIND IT WHERE THEY CAN GET IT. SO WE HEARD FROM THEM ON NUMBER OF OBSTACLES AND COMMON THEMES OBSTACLES ARE THE CHALLENGE IN FINDING ENOUGH FUNDING TO PROTECT THEIR RESEARCH TIME, A THEME WE HEARD AMONG PEOPLE WHO WERE NEARING THE END OF THEIR RO1, WHEN THEY GET THEIR RO1 THEIR APPLICATIONS ARE SEGREGATED IN PEER REVIEW, THEY GET A PAY LINE BUMP, SO WE DO THINGS FOR NEW INVESTIGATORS AND THEN FIVE YEARS LATER THEY HAVE TO COMPETE WITH LABS THAT HAVE BEEN AROUND A LOT LONGER AND HAVE MUCH MORE RESOURCES. SO SOME SUGGESTIONS, THE WAY TO MAKE THAT TRANSITION A LITTLE EASIER. SO MANY SAID THEY NEED TO FIGURE HOW TO BETTER INCREASE EXPOSURE, GET NATIONAL REPUTATIONS, SEEK OUT SPEAKING OPPORTUNITIES AND COMMITTEE SERVICE THAT SORT OF THING. WE HEARD FROM SOME IT COULD BE HARD THE FIND QUALITY GRAD STUDENTS AND POST-DOCS, AND IT DEPENDS ON WHERE THEIR INSTITUTION IS. IF IT WAS NOT A LOT OF THINGS BRINGING QUALIFIED CANDIDATES TO THAT AREA, THEY HAVE TO RELY ON WHO WAS THERE LOCAL. ONE THING SURPRISING IS I ASSUME THAT IN CURRENT ENVIRONMENT OF ONLINE COMMUNICATIONS, SO FORTH, SETTING UP AND MAINTAINING REMOTE COLLABORATIONS, WOULD BE RELATIVELY EASY. AND I THINK THAT MAYBE TRUE FOR VARIOUS ESTABLISHED INVESTIGATORS TO GO TO MORE MEETINGS AND HAVE EXISTING NATIONAL REPUTATION THAT REMOTE COLLABORATION MAYBE AN EASIER THING BUT FOR NEW INVESTIGATORS, IT SEEMS THAT THERE'S NO SUBSTITUTE OF HAVING THAT LOCAL GROUP OF RESEARCHERS WITH SIMILAR INTEREST TO THEIRS. SO WE REALLY HEARD FROM SEVERAL PEOPLE ABOUT HOW THEY ARE DEPENDENT ON COLLABORATORS AND LOCAL ENVIRONMENT AND THE RESOURCES RESEARCH MEETINGS SIMILAR OPPORTUNITIES AND EVERYTHING THAT COMES OUT OF THAT. I THINK SELECTING WHERE A NEW INVESTIGATOR GOES TO SET UPSHOT MAKES A REALLY BIG DIFFERENCE IN LIKELIHOOD OF SUCCESS. SO WE HAD NEW RECOMMENDATIONS FROM THE INVESTIGATOR AND DIVIDED INTO FUNDING AND THE NEXT SLIDE IS MORE IN THAT KIND OF EXPOSURE AREA. BUT IN TERMS OF FUNDING, I THINK THERE WAS THE PERCEPTION THAT A LOT OF NIH AND PRIVATE FUNDING TENDS TO BE CONCENTRATED IN POST DOC AND TRAINEE KIND OF LEVEL AND THESE NEW INVESTIGATORS FELT IT WOULD BE BETTER IF IT WERE MORE EVENLY DISTRIBUTED, THEY FELT THERE WEREN'T SO MANY OPPORTUNITIES FOR NEWLY INDEPENDENT INVESTIGATORS TO BE APPLYING FOR RESEARCH OR SOME OF THE PRIVATE FOUNDATIONS WANT IN ORDER RESTRICT THEIR FUNDING FOR SAY TRANSLATIONAL RESEARCH AND THAT IF THEIR RESEARCH DIDN'T FIT INTO THAT CATEGORY THAT THEY FELT AT A DISADVANTAGE. THEY ALSO LIKE TO SEE MORE COORDINATION WHAT WE TALKED ABOUT AMONG FUNDING ORGANIZATIONS TO REDUCE THIS GRANT WRITING BURDEN AND THE ON PAR SYSTEM IS A STEP TOWARDS THAT BUT AS WE SAID, THERE'S SOME LIMITATIONS TO IT. I MENTION THAT INVESTIGATOR SCORE BUMP ON THE FIRST RO1 AND RELATIONS FROM PEEP WELL TALK TO IS THERE NEEDS TO BE A RENEWAL BUMP. THERE IS AN INTEREST IN HAVING AN ONLINE REPOSITORY FOR ALL FUNDING OPPORTUNITIES PUBLIC AND PRIVATE AS A ONE STOP SHOPPING FOR LOCATING FUNDING OPPORTUNITIES AND MORE SUPPORT FOR TRAVEL OF NEW INVESTIGATORS TO GO TO MEETINGS WILL HELP IN EXPOSURE NETWORKING PEER MENTORING AND THAT SORT OF THING. CONTINUING THAT THEME OF CONFERENCES AND HOW THEY LEAD TO NEW INVESTIGATOR SUPPORT THERE IS INTEREST IN NEW INVESTIGATORS IN SESSIONS REGIONAL OR NATIONAL MEETINGS ON MORE CAREER DEVELOPMENT TOPICS. TOM AND I WENT TO THE MUSCLE STUDY GROUP MEETING IN UTAH AND THEY HAD A WHOLE SESSION, MENTORING AND BREAK OUT SESSIONS WITH EXPERIENCED MENTORS TO HELP NEW INVESTIGATORS BOTH TRAIN TRAINEES AND NEWLY INDEPENDENT FIGURE OUT WHAT THEY NEEDED TO BE ASKING FOR, HOW TO ASK FOR THE TYPE OF MENTORING THEY NEED. I THINK WE HEARD EARLIER, KATHRYN'S TALK ABOUT PERHAPS SESSIONS AT MEETINGS TO SHOWCASE NEW INVESTIGATOR RESEARCH. I DON'T THINK I SEE THAT AT MEETINGS WHERE YOU HAVE THE NEW UP AND COMING NEW INVESTIGATORS BUT THAT MIGHT BE A GOOD THING. SO WE ALSO HEARD RECOMMENDATIONS FOR CONFERENCES TO PROMOTE DISCUSSIONS AND COLLABORATIONS AMONG CLINICAL BASIC RESEARCHERS. MY EXPERIENCE IS MANY DISEASE FOCUS MEETINGS DO INCLUDE BOTH BASIC AND CLINICAL INVESTIGATORS. SO I'M NOT QUITE SURE WHERE THAT'S COMING FROM. SO WE HEARD FROM SEVERAL INVESTIGATORS THAT THEY FELT THEY GOT A LOT OF BENEFIT SERVING FOR PEER REVIEW COMMITTEES, EITHER FOR MDA OR OTHER FOUNDATIONS OR FOR AD HOC SERVICE ON NIH THAT LED TO NETWORKING INCREASE OF EXPOSURE OF THEIR WHAT THEY CAN DO AND WHAT THEY DO IN THE FIELD. I THINK THE RECOMMENDATION TO FIND MORE OF THESE APPRENTICE OPPORTUNITIES. CSR HAS A PROGRAM FOR EARLY STAGE REVIEWER OR SOMETHING LIKE THAT, WHERE A JUNIOR INVESTIGATOR CAN GO ONLINE AND REGISTER, TO VOLUNTEER TO SERVE STUDY SECTION BUT I HAVEN'T SEEN MANY ON STUDY SECTION SO MAYBE THAT NEEDS TO BE BETTER PUBLICIZED. BECAUSE THAT'S HELPFUL FOR NEW INVESTIGATORS AND THEN RESPOND -- >> ON AD HOC BASIS. >> >> YES, IT'S AD HOC AND USUALLY CO-ASSIGNED TO E REVIEW THINGS SO THEY'RE NOT DRIVING A SCORE BUT THEY'RE MORE LEARNING HOW THE PROCESS WORKS. SO THERE WAS INTEREST TO FACILITATE MENTORRENING THE RESEARCH FIELD. I'LL TALK IN A LATER SLIDE. FOR PHYSICIAN SCIENTISTS THEY HAVE SPECIAL NEEDS, WE HEARD THE VALUE OF EVEN SMALL GRANTS OF A COUPLE OF THOUSAND DOLLARS FOR FELLOWS TO GET STARTED IN RESEARCH. JUST TO BE RECOGNIZED WITH AWARD TO THEMSELVES SO THEY CAN START WORKING ON A PROJECT AND IDENTIFY THEMSELVES AND BEING RESEARCH TRACK. FOR RARE DISEASES ESPECIALLY MUSCULAR DYSTROPHIES, YOU REALLY HAVE TO BE AT A PLACE WHERE YOU CAN PARTICIPATE IN A COLLABORATIVE RESEARCH NETWORK. OTHERWISE YOU CAN'T GET ACCESS TO SAME PATIENT RESOURCES. THEN WE HEARD FROM ONE INVESTIGATOR, I THOUGHT WAS VIEWPOINT SHARING OF CLINICAL DATA SETS PROVIDES OPPORTUNITIES FOR CLINICAL FELLOW TO BE ABLE TO INVEST TIME THAT'S FLEXIBLE TIME TO DO RESEARCH. AND DEVELOP ENOUGH RESULTS TO PUT IN ABOUT TRACTS TO GO TO MEETINGS, TO GET PUBLICATIONS OUT OF IT TO START TO LAUNCH RESEARCH EXPERIENCE IS DONE NOT NECESSARILY THROUGH STARTING CLINICAL PROJECTS THEMSELVES BUT HAVING ACCESS TO CLINICAL DATA SETS AT THEIR INSTITUTION OR FROM OTHER PLACES. WE'RE TALKING THIS MORNING ABOUT THE VALUE OF SHARING CLINICAL DATA IF WE DO THAT, ALSO INCLUDE THIS KIND OF SECONDARY DATA ANALYSIS AS A PRIORITY, THAT HELP MORE CLINICAL INVESTIGATORS STARTED IN RESEARCH PROGRAMS. THIS IS JUST FROM THOSE RECOMMENDATIONS A LIST OF POSSIBLE ACTION ITEMS OR THINGS THAT MDCC MEMBER OR ORGANIZATIONS COULD WORK ON. SO ONE OF THE THINGS WE HEARD IS THIS CONSIDER ESTABLISHING A REPOSITORY OF PUBLIC AND PRIVATE FUNDING OPPORTUNITY ANNOUNCEMENTS. SO THAT'S JUST SET UP WEBSITE, WE CAN POTENTIALLY DO IT ON THE MDCC WEBSITE. PUTTING TOGETHER THE FIRST TIME IS WORK BUT IT'S MAINTAINING IT OVER TIME THAT REALLY NEEDS TO BE CONSIDERED. BUT IF DONE PROPERLY IT COULD BE AN ADVANTAGE FOR THE FIELD. CONSIDER WAYS WHEN WE HAVE GRANT SOLICITATIONS THAT WE CAN BETTER COORDINATE FORMAT OF A GRANT OR HOW THE APPLICATIONS ARE USED TO REDUCE BOTH INVESTIGATOR REVIEWER BURDEN, LOOKING INTO EXPANSION ON PAR OR OTHER STRATEGIES. SO WE CAN CONSIDER WAYS TO INCREASE THE VISIBILITY OF NEW INVESTIGATORS. SO ONE OF THE SUGGESTIONS WAS A SPECIAL SESSION AT CONFERENCES, ONE OF THE OTHER NIH INSTITUTES NIDCR DENTAL CRANIOFACIAL RESEARCH EVERY YEAR THEY PRINT A BOOKLET OF THEIR NEW INVESTIGATOR AWARDS, IT HAS A PICTURE, THEIR ABSTRACT, PUBLICATION AND THEY HAND THESE OUT AT NATIONAL MEETINGS. AND OTHER PLACES, THAT MAYBE CREATING OPPORTUNITIES OR AT LEAST INCREASING RECOGNITION FOR THE NEW INVESTIGATORS. AND IT IS REALLY OUR LATEST AND GREATEST UP AND COMING CROP OF AWARDEES. SO WE CAN CONSIDER THAT OR OTHER STRATEGIES TO MAKE A COMMUNITY MORE AWARE OF WHO ARE THE NEWLY FUNDED INVESTIGATORS. WE TALKED ABOUT WAYS TO INCREASE APPRENTICESHIPS ON REVIEW PANELS, CONSIDER WAYS TO FACILITATE REMOTE MENTORING RELATIONSHIPS SO AN EXAMPLE IS THE AMERICAN ASSOCIATION OF NEUROLOGISTS, NEUROLOGY, NEUROLOGY -- NEUROLOGISTS, SO THEY HAVE ON THEIR WEBSITE A MENTOR CONNECT, SO EXPERIENCE MENTORS AND NEW INVESTIGATORS OR TRAINEES CAN REGISTER TOPICS OF INTEREST AND HELPS CONNECT THEM TOGETHER, JUST SOME QUESTIONS YOU NEED OBJECTIVE VIEWPOINT, SOMEONE TO GIVE YOU ADVICE ON DIFFERENT ASPECTS, SO THAT MAY BE ALREADY AVAILABLE TOKER CLINICAL NEUROLOGISTS BUT COULD BE VALUABLE FOR OTHER INVESTIGATORS IN THE FIELD. BY PROMOTING INCREASED ACCESS TO CLINICAL DATA WE MAY INCREASE THE ENTRY OF CLINICALLY TRAINED INVESTIGATORS INTO THE FIELD. SO THIS LAST SLIDE, THIS IS MY DIAGRAM TO TRY TO PUT ALL THE SESSION TOGETHER AND IT'S A SCIENTISTS ATTEMPT AT GIVING THE ILLUSION THAT WE LOOK AT THIS OBJECTIVELY. BUT WHAT I SHOW HERE IS THE DIFFERENT STAGES THAT WE CAN THINK OF FROM GOING FROM A TRAINEE TO A TENURED ACADEMIC INVESTIGATOR AND ALL THE BRANCH POINTS OR DECISION POINTS THAT GO -- THAT TAKE PLACE ALONG THE WAY. SO HERE BY PHYSICIAN, I MEAN SOMEONE JUST DOING CLINICAL CARE RELATED ACTIVITIES BUT ALL THE REST OF THESE COULD BE PHYSICIAN SCIENTISTS OR SCIENTISTS THAT DON'T HAVE CLINICAL TRAINING. SO TRAINEE, THAT HAS TO MAKE A DECISION WHETHER TO JUST DO CLINICAL WORK OR BECOME ACADEMIC NEW INVESTIGATOR OR GO INTO INDUSTRY, AND THEN THERE'S SOME BACK AND FORTH HERE. OPPORTUNITIES FOR PEOPLE DOING CLINICAL WORK TO GET INTO RESEARCH MORE MIGHT BE A GOOD OPPORTUNITY. SOME ACADEMIC NEW INVESTIGATORS WOULD BE GOING INTO INDUSTRY ALTHOUGH I GUESS KEVIN HAD THE EXPERIENCE OF POST DOC WHOSE MAKE A DECISION WHETHER TO GO INTO ACADEMIC CAREER OR GO INTO AN INDUSTRY CAREER BUT WHAT I HAVE SEEN MORE IS TRAINEES KNOW WHETHER THEY WANT ACADEMIC OR INDUSTRY, BEEN POST DO, THEY MADE THAT -- DRIVEN POST-DOC, HOW DIFFICULT IT IS TO GET FUNDING FOR THEIR OWN LABS SO WE EMPHASIZE THE TRANSITION FROM AN ACADEMIC NEW INVESTIGATOR INTO AN RO1 PRINCIPLE INVESTIGATOR. AND SOME PEOPLE ARE NOT AS SUCCESSFUL AS OTHERS IN MAKING THAT TRANSITION BUT MAY GET FUNDING FROM OTHER PUBLIC AND PRIVATE SOURCES. I THINK WHAT WE ARE ALSO SEEING IS NEW INVESTIGATORS THAT CAN'T GET AN RO1 APPLY FOR R21s, MAYBE SUCCESSFUL WITH THAT. PRIVATE FUNDING TO KEEP A SMALL PROGRAM GOING QUITE SOME TIME AS THEY APPLY FOR RO1. SIMILARLY, PEOPLE WHO HAVE AN RO1 BUT LOSE IT MAY STEP BACK AND CONTINUE TO HAVE PRIVATE FUNDING OR R21 FUNDING, ANALYSIS THAT NINDS DID SHOWED THAT THERE ARE A NUMBER OF LABS SURVIVING ON R21 SUPPORT. AN RO1 IS A LOT OF TIMES CREDENTIALS NEEDED TO MOVE INTO A TENURED POSITION TO GET THIS STABILITY AND WHILE WE SEE PEOPLE DIFFERENT STAGES GOING INTO INDUSTRY, WE HAVE ALSO SEEN TENURED ACADEMIC INVESTIGATORS IN THIS FIELD THAT START COMPANIES AND CONTRIBUTE TO INDUSTRY RESEARCH. SO I THINK WE SHOULD CONSIDER ALL OF THESE INVESTIGATORS TO BE VALUABLE IN THE FIELD. AND WE WANT TO CONSIDER THE RELATIVE BALANCE. CAN WE FIGURE OUT WHAT GOES INTO EACH DECISION MAKING POINT, SO THAT WE ESSENTIALLY HAVE KNOBS THAT WE CAN TURN TO REGULATE KINETICS OF THIS EQUATION, TO TRY TO MOVE PEOPLE INTO DIFFERENT PARTS OF THE FIELD. IT'S WORTHWHILE TO ASK WHY ARE RO1 INVESTIGATORS AND TEN YOURED ACADEMIC INVESTIGATORS WHY EMPHASIZE THEM OVER OTHER PEOPLE IN THE FIELD. I THINK IT'S REASONABLE TO SAY THAT RO1 AWARDEES AND TENURED ACADEMIC INVESTIGATORS THAT CREATE NEW JOBS IN WORK FORCE, THEY HIRE GRAD STUDENTS AND POST-DOCS AND TECHNICIANS, SO FORTH AND THEY TRAIN A LOT OF NEW PEOPLE TO KIND OF FEEDBACK INTO THIS LOOP. THEY'RE CERTAINLY NOT RESPONSIBLE FOR ALL THE INNOVATION AND DISCOVERY IN THE FIELD, BUT A LOT DOES HAPPEN IN THESE STABLE WELL SUPPORTED LABS. THIS IS JUST MY VIEW OF WHAT THE LANDSCAPE LOOKS LIKE AND WHAT WE TALKED ABOUT. BUT MAYBE FOR THE DISCUSSION, IF WE -- >> BEFORE YOU GO I THINK JOAN HAS A QUESTION. >> DID YOU TALK TO YOUR ON THE FAR LEFT? WHAT WAS THE INITIAL HOOK? GETTING TO THE PIPELINE IS ANOTHER CONVERSATION BUT EXPOSURE TO SOMEONE DOING WORK IN THE AREA, EXPOSURE TO A FAMILY, WHAT WAS THE ORIGINAL LOOK? >> WE HAVE ASKED THAT QUESTION, I KNOW HEATHER ASKED THAT QUESTION TO PEOPLE WE TALKED TO. SEEMED TO BE EARLY EXPERIENCES IN COLLEGE WHERE THEY HAD RESEARCH OPPORTUNITIES AND THEIR FIRST EXPERIENCES IN RESEARCH WHERE THEY GOT EXCITED ABOUT SOME LAB THAT WAS DOING MUSCULAR DYSTROPHY RELATED STUFF. I KNOW THERE'S CERTAINLY OTHER PEOPLE IN THE FIELD THAT HAVE FAMILY MEMBERS THAT ARE AFFECTED BY DYSTROPHIES. THAT'S A DRIVING FORCE FOR THEM TO COME INTO THE FIELD. SO FOR THIS ANALYSIS OR WHAT WE WERE TALKING ABOUT TODAY, WE'RE REALLY TRYING TO FOCUS ON THIS ACADEMIC NEW INVESTIGATOR BUT WHAT WE MAY WANT TO DO FOR A SESSION AT A FUTURE MDCC MEETING IS TALK MORE ABOUT HOW TO BRING PEOPLE IN TO THE TRAINEE STAFF AND EXAMINING THAT SPECIFIC LOOK AND WHETHER ADDITIONAL FUNDING FOR FELLOWSHIPS BRING MORE PEOPLE IN AND WHAT IMPACT THAT WOULD HAVE. >> OF COURSE LOOK AT THIS, UNLESS YOU HAVE A ROBUST TRAINEE PROGRAM, THE DROWN STREAM IS LIMITED. SO THAT'S REALLY -- DOWNSTREAM IS LIMITED SO CON WHERE THE CONCENTRATION HAS TO BE. I HAVE A SPECIFIC QUESTION. AT THE ANNUAL MEETING OF THE WELLSTONE CENTERS, ARE NEW OR EARLY STAGE OR TRAINEES WHO ARE NOT CONNECTED TO WELLSTONE CENTERS ARE THEY CONNECTED TO THE MEET SOMETHINGS >> THE LOCAL ONES ARE. THE ONES FROM THE OTHER SENATE, THE SENATE HAVE LOCAL MEETING PARTICULAR SENATE EACH YEAR. SO SEATTLE HAS THE MEETING THE LO DABBLE INVESTIGATORS WERE THERE BUT THE IOWA INVESTIGATORS, THERE'S ONLY PEOPLE IN THE WELLSTONE CENTER. >> CLEARLY THAT CAN BE A PLACE AND INVITE PEOPLE. >> TALK TO ALL OF YOUR OWN PEOPLE,NAs A GOOD THING AND GET THAT RECOGNITION. SO IT'S NOT JUST A CLUB. >> RIGHT NOW MOST WELLSTONE FACE TO FACE MEETINGS ARE RUN BY LOCAL COMMITTEE AND IT'S KIND OF GIFT ONCE THEY GET TOO BIG TO HAVE THEM >> WE CAN CONSIDER HAVING A WELLSTONE MEETING ANCILLARY TO NATIONAL MEETING OF SOME TYPE SO THERE'S MORE PEOPLE THERE AND THAT WOULD HELP GET MORE EXPOSURE WHAT'S GOING ON IN THE CENTERS. >> ARE THERE T 32 GRANTS THAT FOCUS ON DYSTROPHIES? >> NOT IN NIAMS. IN MUSCLE, YES. FROM BUT NOT MUSCULAR DYSTROPHIES. >> SO MIGHT THIS BE AN AREA -- >> FROM NIMS, I CAN'T SPEAK TO NINDS SO THIS MIGHT BE AREA FOR POTENTIAL FUTURE TRAINING OPPORTUNITIES TO STIMULATE THE MORE ESTABLISHED COMMUNITIES TO THINK ABOUT THAT BUT ALTERNATIVELY, WE HAVE DONE THIS IN NHLBI AS WELL, SUPPLEMENT EXISTING T 32s TO ENHANCE THE TRAINING OF PEOPLE INVESTIGATORS NEW INVESTIGATORS, WHATEVER, CLINICAL OR PRE-OR POST DOCS FOR THAT MATTER, IN THIS AREA SO YOU CAN KIND OF GIVE AN INCENTIVE WITH ADDITIONAL SLOTS OR SOMETHING TO THOSE WHO ESTABLISH T 32 AWARDS TO BRING ON PEOPLE THAT INCREASE THE POOL. THAT'S WHERE CLEARLY THERE IS A NEED. I DON'T KNOW IF YOU LOOK INTO THAT, BUT THAT MIGHT BE A WAY TO HELP BRING NUMBERS UP AND GET THAT ENVIRONMENT AND EXPOSURE THAT YOU HAVE BEEN REFERRING TO. IN PLACE TO HELP ATTRACT ADS WELL AS PROVIDE NECESSARY ENVIRONMENT TO SUCCEED. >> SO THAT TOP POINT ACTUALLY SOME UNIVERSITIES DO THAT REALLY WELL. IOWA DOESN'T BUT I KNOW HENRY DOES SO AT EMORY IF YOU SIGN UP, THEY'LL FIND EVERYTHING FOR YOU. SO YOU MIGHT LOOK INTO WHAT UNIVERSITIES ARE DOING REALLY WELL, MIGHT HELP. >> IT GOES WELL BEYOND THAT, THE DORIS DUKE FOUNDATION, THE WELCOME FOUNDATION, I WON'T SAY ENDLESS BUT THERE'S ENORMOUS POSSIBILITIES OF GROUPS THAT ARE PARTICULARLY INTERESTED IN WHAT VALERIE WAS TALKING ABOUT IN TERMS OF TRANSLATIONAL AND CLINICAL RESEARCH TO ENCOURAGE PEEPER WORK. THOSE ARE GENERIC. BUT NOT TO SAY THEY WOULDN'T EMBRACE AN OUTSTANDING INVESTIGATOR. S WHO WORKING ON MUSCULAR DYSTROPHY. SO IT'S A BIG, BIG WORLD OUT THERE. >> I WAS GOING TO COMMENT I DON'T THINK IT'S AN ACCIDENT YOU FIND EXCELLENT REPOSITORIES AT MOST BEST FUNDED PLACES IN THE COUNTRIES. I KNOW I HAD -- THAT WAS THE UNIVERSITY OF NORTH CAROLINA FOR A LONG TIME, WE HAD A FAIRLY CRUMB MY RESEARCH OFFICE THAT DID SUCH A GOOD JOB BUT CLOSE COLLEAGUE MOVE TO HOPKINS AND PEOPLE WERE COMING TO HER WITH ALL KINDS OF OPPORTUNITIES >> UNIVERSITY OF PENSACOLA HAS A VERY GOOD. >> -- UNIVERSITY OF PENNSYLVANIA HAS A GOOD -- >> WE CAN'T -- IOWA AND OTHER INSTITUTIONS THAT HAVE TYPICALLY THE RULE WILL ALLOW YOU IF YOU HAD TO HAVE AN RO1 TO GET TENURE, CURRENTLY THERE'S TALK ABOUT PROMOTING WITH RO1 ASSOCIATE PROFESSOR BUT TENURE WOULDN'T COME UNTIL YOU RENEWED RO1 OR GOT A SECOND ONE. SO RENEWAL FIRST RO1 IS GOING TO BE REALLY IMPORTANT TO MAINTAIN IN ACADEMIC RESEARCH, IF THE STATE IS NOT REQUIRING THAT, IT'S REALLY IMPORTANT TO DO THAT. >> WE ALSO REWARD THAT WITH OUR I THINK I WAS MENTIONING TO YOU THE STAR PROGRAM THAT WE HAVE, PEOPLE WHO RENEW THEIR FIRST RO1 ARE ELIGIBLE FOR A SIZE SUPPLEMENT TO TAKE THEIR PROJECT INTO A PROGRAM. WHICH IS WHAT WE'RE LOOKING TO DO. >> THOSE ARE ALTHOUGH KIND OF NIH WIDE I GUESS IT WAS LIKE BY SEVEN OR EIGHT YEARS THERE'S 50% LOSS OF PREVIOUSLY RO1 FUNDED INVESTIGATORS. THOSE ARE PEOPLE THAT REALLY HAD BIG INVESTMENTS IN. THEY HAVE LABS, THEY HAVE POST-DOCS AND GRAD STUDENTS SO THE UM PACT OF LOSING THOSE PEOPLE SIGNIFICANT. SO I THINK FIGURING HOW TO ADDRESS THAT RATE IS QUITE IMPORTANT. >> OKAY. THANK YOU VERY MUCH. [APPLAUSE] >> DAN YOU HAD A QUESTION? >> I HAD A QUESTION AND (INDISCERNIBLE) PARALLEL COROLLARY. AS YOU LOOK AT THE GLANCE, I'M SURE STUDY SECTIONS RECOGNIZE WORK TRANSFORMATIVE AND WORK THAT'S REALLY GOING TO MAKE A DIFFERENCE IN AN AREA, YOU HAVE TO DO EXCELLENT GRANTS, CERTAIN GRANTS ARE NARROW, VERY WELL WRITTEN. OTHERS WILL HAVE A LASTING IMPACT. I DON'T KNOW IS THERE A WAY TO ASSESS MUSCULAR DYSTROPHY HOW DO YOU GET THE STUDY SECTION TO RECOGNIZE, THAT'S COUNTER TO WHAT DR. NUCKOLLS WAS TALKING ABOUT IN TERMS OF LOSS OF LONGEVITY, LONG STANDING RESEARCHERS. THEN THE OTHER QUESTION TO DR. CHEEVER AND NUCKOLLS, IS THERE CONSIDERATION TO DO -- FDAR GENERALLY HIGHLIGHTS INTEREST IN ALL MUSCULAR DYSTROPHYs OR PARTICULAR DYSTROPHIES NOT DOING WELL IN TERMS OF APPLICATIONS. >> LET ME ANSWER THAT, NO GROUP IS DOING WELL IN TERMS OF APPLICATIONS, UNFORTUNATELY. THAT'S A FACT OF LIFE. WITH REGARD TO SPECIFIC POINT, THE IMPACT YOU SHOULD KNOW NIH DIRECTORS PUT OUT AN ANNOUNCEMENT THAT IMPACT PUBLIC HEALTH IMPACT WAS REMOVED FROM THE OR THE WORDING WAS CHANGED BECAUSE IT WAS FELT THAT WE WERE MOVING AWAY FROM BASIC RESEARCH. BASIC RESEARCH HAD BEEN ONE OF THE FOUNDATIONS OF THE NIH AS YOU KNOW. SO MANY DISCOVERIES THAT WE TALKED ABOUT TODAY EMANATE FROM BASIC -- REALLY VERY BASIC RESEARCH. SO FOR US TO SAY WE'RE LOOKING FOR ULTIMATE IMPACT ON A CLINICAL PROBLEM, WE'RE RETICENT TO SAY THAT BECAUSE THAT WOULD BREAK THE BALANCE AND WE DO HAVE A BALANCE AND WE HAVE ACTUALLY GOTTEN LANGUAGE THAT TALKS ABOUT THE NIH NEEDING TO DO MORE IN THE WAY OF BAY SUCK RESEARCH. -- BASIC RESEARCH. BUT DO WE BEYOND STUDY SECTION, DO WE AS INSTITUTE LOOK AT THAT, OF COURSE WE LOOK AT THAT. WE LOOK AT MANY THINGS IN TERMS OF FUNDING DECISIONS. THE STUDY SECTIONS MAKE CERTAIN RECOMMENDATIONS. WE IN THE INSTITUTES MAKE DECISIONS. DO YOU WANT TO ADD ANYTHING? ALAN? >> I THINK THAT COVERS THE STRATEGY THAT WE USE PRETTY WELL. SIGNIFICANT FRACTION OF THE AWARDS WE MAKE AT NINDS ARE DRIVEN NOT JUST BY SCORE BUT BY AREAS THAT WE THINK WE NEED MORE IN SO RATHER THAN FUNDING 7TH GRANT WE'LL REACH A LITTLE BIT AND GET GRANT IN AN AREA YOU DON'T HAVE MUCH GOING ON. WE LOOK CLOSE AT PEOPLE WHEREAS FIRST RENEWAL IS MAJOR POINT OF EMPHASIS FOR US IN TERMS OF FUNDING DECISIONS. OBVIOUSLY WE ALWAYS HAVE LONGER LIST OF THINGS WE WOULD LIKE TO FUND THAN DOLLARS AVAILABLE BUT EVERY ROUND THERE'S CAREFUL SCRUTINY OF SIGNIFICANT SET OF APPLICATIONS BEYOND AUTOMATIC PAY LINE AND THOSE FACTORS WE TALK ABOUT GO INTO IT. >> APPLICATION OF FRUITFULNESS OF MODEL SIMILAR APPROACH AT THIS TIME? SO SOMETHING WHERE THERE WOULD BE COMMON DATA ELEMENTS AND DATA SHARING AMONG VARIOUS CENTERS WORKING ON VARIOUS APPROACH? OR IS THAT NOT USEFUL? >> IT WOULD BE EXTRAORDINARILY USEFUL IF WE CAN FIGURE OUT HOW TO OPTIMIZE IT. NOW IT'S ENCOURAGED SO THE WELLSTONE CENTERS CLEARLY THAT ARE MEANT NATIONAL CENTERS WITH CERTAIN FOCI OF EXPERTISE. BUT OBVIOUSLY NOT ALL WILL BE DUCHENNE, NOT OWL MYOTONIC DYSTROPHY, SOME IS FSHD, WE'RE LOOKING TO MAXIMIZE OUR INVESTMENT. THAT'S A FAIRLY LARGE INVESTMENT ACROSS THE NIH. >> I OOH HE WILL NOT IN THE RESEARCH -- >> THAT'S THE QUESTION. >> FROM THE GOVERNMENT PERSPECTIVE, I REALIZE THESE ARE NOT EMPLOYEES, BUT WE SPEND A LOT OF TIME TALKING ABOUT ENGAGEMENT. ABOUT HOW INVOLVED THE PERSON IS IN THE WORK THEY DO. AND HOW SATISFIED THEY ARE. WHAT THEY ARE UNHAPPY WITH AND WHAT THEY'RE HAPPY WITH. ADS A PARENT OF TWO MILLENNIALS, I KNOW THEY DON'T WANT TO WORK 24/7. I'M WONDERING IF YOU THINK ABOUT WORK LIFE BALANCE EMPLOYEE ENGAGEMENT KINDS OF THINGS AS YOU TALK ABOUT DROP OFF OR LESS PEOPLE INVOLVED, LESS YOUNGER PEOPLE BEING INVOLVED BECAUSE I KNOW EVEN GOVERNMENT WIDE I SEE A CHANGE IN HOW WE APPROACH DEALING WITH YOUNGER PEOPLE NOW. >> I PERSONALLY THINK THAT'S AN EXCELLENT COMMENT HAVING THREE MILLENNIALS I WOULD TELL YOU THE SAME IS TRUE OF MY CHILDREN. IT TURNS OUT THEY ARE ON THEIR ELECTRONIC MEDIA WHETHER IT'S FOR WORK OR WHETHER IT'S FOR PLEASURE BUT VERY OFTEN FOR WORK. ALMOST 24/7. SO YOU TAKE ONE WHO IS A PHYSICIAN AT KEISER, HE'S CONSTANTLY ON CALL BASICALLY. BECAUSE HIS PATIENTS -- HE'S INTERACTING WITH HIS PATIENTS BY EMAIL ELECTRONICALLY. IN TERMS OF DOING WHAT SOME OF US DID IN THE LABORATORY BEING THERE ALL THE TIME, YOU'RE RIGHT. IT'S NOT FOR THEM. PARTICULARLY IF YOU COMPLAIN YOUR FELLOWS, YOU'RE SUPPOSED TO COMPLAIN TO YOUR SPOUSES AND ADMINISTRATORS, YOU'RE NOT SUPPOSED TO COMPLAIN TO YOUR FELLOWS. IF YOU'RE DOING IT THAT MEANS YOU GET SOME SATISFACTION SOME GREAT SATISFACTION AND I'M SURE DR.S WAGNER AND CAMPBELL NOT COMPLAIN TO THEIR FELLOWS WHAT THEY'RE DOING. GREAT SOURCE. OF SATISFACTION. >>TY CAN IMAGINE THAT MAYBE ANOTHER SOURCE OF DROP -- I DON'T WANT TO WORK AS HARD AS YOU AS YOU WORKED. >> SOME OF THE POST-DOCS FROM INDUSTRY TO MY LAB CLEARLY THEIR SPOUSE SAYS I DON'T WANT YOU TO WORK AS HARD AS KEVIN HAS TO WORK BUT TO BE HONEST, ONCE THEY GET THE INDUSTRY THEY REALIZE THE SAME THING HAPPENS THERE. SO PREVIOUS LIKE ONE IS A MILLENNIAL, HE WAS SENT TO INDIA TWO WEEKS, BUYING THE COMPANY, IT WAS HIS SON'S BIRTHDAY, DIDN'T MATTER, WE SEE THE FLEXIBILITY, MIGHT BE WORKING DAY AND NIGHT BUT YOU CAN STAY HOME FOR YOUR SON'S BIRTHDAY SO I THINK THERE'S -- THEY DON'T KNOW THE OTHER SIDE. A LOT OF JOBS TODAY ARE GETTING VERY COMPETITIVE. BUT I AGREE WITH YOU ABOUT SPENDING THE TIME. WHAT WE'RE FINDING SOME OF THE MENTORING ASPECTS THE OFF HOURS, THE YOUNG PEOPLE DON'T WANT TO DO THAT. THEY WANT THEIR FREE TIME. >> I THINK THERE WERE MANY POINTS, GOOD TIME TO SUM UP. WE HAD A LONG DAY, IT'S BEEN A VERY INTERESTING DAY. TO JUST SUM UP WHAT WE HAVE JUST HEARD. IN TERMS OF NEW INVESTIGATORS AND DIFFICULT TIME IN GETTING RESEARCH FUNDING AND FINDING THE RIGHT WORK LIFE BALANCE. I THINK WE NEED TO CONSIDER MANY OF THE THINGS THAT GLENN PUT UP ON THE -- ON HIS BASICALLY YOUR SUMMARY SLIDE IN TERMS OF ACTION ITEMS. OF POTENTIAL ACTION ITEMS. I THINK THAT THE GROUP SHOULD PROBABLY RESPOND TO SOME OF THOSE. IN IF TERMS OF THINKING WHETHER THIS SHOULD BE NIH ACTIVITY OR NOT AN ACTIVITY AT ALL BUT WE LIKE TO HEAR FROM YOU IS THAT WE CAN AT OUR NEXT MEETING SORT OF RESPOND TO THE RESPONSES THAT WE HAVE RECEIVED. IT'S OFTEN DIFFICULT TO THINK ABOUT WHAT ARE COLLECTIVE RESPONSIBILITIES TO COVER ALL THE WATER FRONT SO THIS MORNING'S DISCUSSION ON ETHICAL CONSIDERATIONS, I THINK WAS ACADEMICALLY VERY INTERESTING ON A PRACTICAL BASIS, VERY INTERESTING BUT THE QUESTION IS WHAT SHOULD THE ROLE OF THE MDCC BE IN THESE TERMS? I THINK ONE SIMPLE ACTION ITEM IS THOSE -- SOME OF THOSE ARTICLES THAT CENTER AROUND IF NOT SHARED BY EVERYONE THEY SHOULD BE LOOKED AT BY EVERYONE. BUT MY SENSE IS THAT THOSE CONSIDERATIONS FOR MUSCULAR DYSTROPHY, THOSE ARE GERMANE TO ALMOST EVERY -- WHEN I LOOKED AT SOME DETAIL, THEY'RE GERMANE TO ANY ONE OF THE RARE DISEASES WHERE YOU'RE THE RISK AND THE BENEFIT COMES TO PLAY AND THE PATIENT INPUT BECOMES REALLY IMPORTANT. THERE ARE CERTAIN PATIENT REPORTED QUALITY OUTCOME MEASURES THAT CAN BE UTILIZED, ENCOURAGED BY US BUT I THINK THAT WE CAN DO ANYTHING, WE HAVE TO HAVE THIS DISCUSSION T A AN APPROPRIATE TIME, WE DEN HAVE IT LAST MEETING BECAUSE IT WAS TOO SENSITIVE IN TIME FOR THE FDA TO DISCUSS SOME OF THOSE DECISIONS. FINALLY, THE COMMITTEE THAT WE PUT TOGETHER IN TERMS OF ACCESS TO CARE, THERE'S MEAT ON THE BONES. QUESTION IS WHAT ARE SOME OF THOSE ACTION ITEMS AND HOPEFULLY IT IS A EVERY OTHER MONTH MEETING THERE WILL BE AN AGENDA AND THEY WILL BE SOME DISCUSSION NOT ONLY OF REAL DIFFERENCE MAKERS BUT ALSO LOW HANGING FRUIT THAT WE CAN SAY, WELL, SOME ENTITY FROM THE MDCC CAN ACTUALLY TAKE THE RESPONSIBILITY WITH SOME SUPPORT FROM THE MDCC AND CARRY IT OUT. SO I WANT TO THANK EVERYONE FOR BEING HERE. GLENN GETS THE REAL CLOSING REMARKS. I WANT TO THANK GLENN AND COLLEAGUES FOR PUTTING TOGETHER SUCH A VERY, VERY INTERESTING MEETING. >> THANK YOU, I HAVE ENJOYED IT TOO, GREAT TO SEE ALL OF YOU. SO COUPLE OF LOGISTIC THINGS, IF YOU'RE A NON-FEDERAL MEMBER OF THE COMMITTEE, YOU NEED TO -- SOMEWHERE ON THAT FORM WE HANDED OUT SIGN IT AND RETURN IT ON YOUR WAY OUT. SHE ALSO HAS PARKING STICKERS IF YOU'RE PARKING IN OUR COMPLEX HERE. AND OTHERWISE, WE'RE TRYING TO COLLECT DATES THAT WOULD BE SUITABLE FOR A MEETING IN EITHER APRIL OR MAY AND THEN THE SECOND MEETING OF THE YEAR IN OCTOBER OR NOVEMBER WE HAVE CANDIDATE DATES THAT YOU WILL HEAR FROM US IN THE NEXT COUPLE OF WEEKS ABOUT SELECTING THOSE DATES, WE WOULD LIKE TO LOCK THEM IN FOR ALL OF 2017 AND START PLANNING FOR THOSE MEETING DATES. CERTAINLY IF YOU HAVE TOPIC IDEAS THAT YOU WOULD LIKE TO SEE COVERED AT THE MEETINGS, LET ME KNOW. ALWAYS INTERESTED IN EXCITING MEETING TOPICS. AND OTHERWISE GREAT MEETINGS, THANKS, EVERYBODY FOR COMING. RETURN YOUR NAME BADGES ON THE WAY OUT, WE RECYCLE THEM TO MAKE IT ALL AS GREEN ADS POSSIBLE. >> FINALLY WE WANT TO THANK THOSE OF YOU WHO ARE GUESTS OF THE MEETING TODAY, WE APPRECIATE YOUR ACTIVE PARTICIPATION. IT IS GOOD TO SEE Y'ALL AGAIN.