WELCOME, EVERYONE, TO THE JOINT MEETING OF THE ADVISORY COUNCIL AND CAN REVIEW BOARD. IT'S GREAT TO HAVE EVERYBODY HERE. ONCE EVERYBODY ARRIVES, I THINK THIS WILL BE THE BEST-ATTENDED MEETING THAT WE'VE HAD, EVER, WHICH IS WONDERFUL. SO THANK YOU ALL FOR MAKING THE TIME TO BE HERE. WE HAVE A LOT TO GO THROUGH TODAY, SO I WAS BUSY CHIT-CHATTING WITH A NUMBER OF YOU, AND I WAS TOLD WE HAD TO GET STARTED SO WE AT LEAST START ON TIME. WE CAN ALWAYS DREAM THAT WE WILL STAY ON TIME. BUT ONE OF THE REASONS I LIKE THE FACT THESE MEETINGS USUALLY DON'T STAY ON TIME IS BECAUSE ALL OF YOU ARE SO PARTICIPATORY, SO PLEASE, I AM MUCH MORE INTERESTED IN YOUR IDEAS THAN STAYING ON TIME. SORRY. I WILL PROBABLY BE CHASTISED FOR THAT COMMENT AFTER THE MEETING BUT IT REALLY IS TRUE. SO THE FIRST THING WE WANT TO DO IS GAVEL THE MEETING TO ORDER. YOU WILL NOTICE THAT THE PERSON TO MY LEFT MAY LOOK LIKE FREEDA LEWIS-HALL BUT ACTUALLY ISN'T. AND BUT I CAN ASSURE YOU THAT HAS AS GOOD A SENSE OF HUMOR AND AS GOOD A SCIENTIFIC -- GOOD SCIENTIFIC ACUMEN WHO IS LYNN MARKS, WHO IS THE NEW CURRENTLY STILL ACTING CHAIR OF THE CAN REVIEW BOARD, AND I THINK WE CAN GIVE YOU SOME UPDATES ON WHERE WE ARE ON THE SPECIAL GOVERNMENT EMPLOYEE ISSUE BUT MOST OF YOU KNOW THAT. LYNN I THINK MOST OF YOU KNOW HAS BEEN WITH US FOR A NUMBER OF YEARS NOW, IN A NUMBER OF CAPACITIES, UNTIL A FEW MONTHS AGO WAS AT GLAXOSMITHKLINE WHERE HE HAD BEEN FOR A COUPLE OF DECADES, IN A NUMBER OF CLINICAL RESEARCH POSITIONS, AND RECENTLY RETIRED AND IS NOW A CONSULTANT AT BARDA. HE'S AN INFECTIOUS DISEASE DOC BY TRAINING, AND SO PARTICULAR INTEREST TO BARDA. WELCOME, LYNN, AND WELCOME, OUR ACTING CO-CHAIR WHO IS RON BARTEK, MOST OF OF YOU KNOW AS WELL FROM THE RESEARCH ALLIANCE. SO WITH THAT WE'RE GOING TO GAVEL THE MEETING INTO ORDER. SO WE'RE GOING TO GO ONE, TWO, THREE. WHOA! NOW, THAT WAS REALLY QUITE GOOD, I MUST SAY, AS A FIRST TRY. WE DIDN'T EVEN REHEARSE THAT. OKAY. SO WE'RE OFFICIALLY IN SESSION. I JUST WANT TO REMIND YOU THAT THIS MEETING IS VIDEOCAST, SO TO ALL OF YOU WHO ARE WATCHING OUT THERE, WELCOME. WE WILL DESPITE MY COMMENTS TRY TO STAY MORE OR LESS ON SCHEDULE BECAUSE I KNOW SOME OF YOU WILL BE COMING IN AND OUT ON THE VIDEOCAST, ACCORDING TO THE SCHEDULE THAT WE HAVE. SO IN ATTENDANCE TODAY WE HAVE A NUMBER OF AD HOC MEMBERS, THOSE PEOPLE ARE STILL AD HOC BECAUSE OF THE HIRING -- FEDERAL HIRING FREEZE WHICH PREVENTED US FROM MOVING FORWARD WITH ALL OF YOUR OFFICIAL APPOINTMENTS UNTIL VERY RECENTLY. THAT'S THE ISSUE OF SPECIAL GOVERNMENT EMPLOYEES WAS JUST RECENTLY A COUPLE WEEKS AGO, MAYBE A WEEK AGO, RESOLVED. SO WE'RE NOW MOVING FORWARD AND YOU SHOULD ALL BE HEARING SOMETHING VERY SOON ABOUT THAT. BUT THOSE ARE KATHY, JEFF, KALPANA, VALERIE, STEVEN SPIELBERG, SHARON TERRY AND ERIC TOPOL ARE STILL AD HOC. WE WILL HAVE A COUPLE EX OFFICIO MEMBERS, TERRY RAUSCH FROM DoD AND FRANK WICKHOLD FROM THE FDA, ALAN PALKOWITZ FROM LILLY, YOU PROBABLY REMEMBER GOT STUCK IN INDIANAPOLIS WESTBOUND A REQUIRED MEETING AT LILLY TODAY SO HE IS GOING TO JOIN US BY PHONE PROBABLY AROUND 9:45, YEAH. THAT WILL BE VERY IMPORTANT FOR ONE OF THE CONCEPT CLEARANCES LATER. SO PAUL YOK AND STEVE SPIELBERG, DO YOU HAPPEN TO BE ON THE PHONE YET? >> YES. >> GOOD MORNING, YES. >> YOU'RE BOTH THERE? WONDERFUL. THANK YOU, PAUL, FOR GETTING UP SO EARLY. AND GOOD TO HEAR YOUR VOICE, STEVE. NOT PRESENT TODAY IN CASE YOU'RE LOOKING FOR THEM BRAD, ROJ, RACHEL AND TODD SCHERER. WE HAVE A COUPLE OF INVITED SPEAKERS, I WANT TO RECOGNIZE STAN AHALT IN THE GREEN TIE PARTICIPATING IN THE TRANSLATOR SESSION, AND GORDON BERNARD, WHERE IS HE? THERE HE IS IN THE BACK ROW IS GOING TO BE PARTICIPATING IN THE IRB SESSION THIS AFTERNOON, LEE AND BARBARA SHOULD BE HERE SHORTLY TO PARTICIPATE IN THAT SESSION AS WELL. LET ME GO THROUGH BRIEFLY THE AGENDA WITH YOU SO YOU KNOW WHERE WE'RE GOING. MOMENTARILY I'M GOING TO TURN THIS OVER TO ANNA, WHO IS GOING TO TALK TO US ABOUT THE LOGISTICAL ISSUES APPROVAL OF MINUTES, CONFIRMATION OF FUTURE MEETING DATES, ET CETERA. THEN I WILL GO THROUGH MY DIRECTOR'S REPORT, WE HAVE A LITTLE BIT OF A DIFFERENCE IN THE ORDER THAN WHAT WE'VE DONE PREVIOUSLY. AFTER THE BREAK WE HAVE FOUR CONCEPT CLEARANCES. WE NEED YOU TO ADVISE US ON. A NUMBER OF THEM ARE NEW AND VERY EXCITING, SO I LOOK FORWARD TO HEARING WHAT YOU THINK ABOUT THOSE. AND THEN WE'RE GOING TO HAVE AN UPDATE ON THE TRANSLATOR PROGRAM THAT IF YOU DON'T WHAT THAT IS I THINK YOU'LL REMEMBER QUICKLY WHEN CHRISTINE COLVIS STARTS TO TALK ABOUT THAT FROM NCATS, AND STAN, WHO IS ONE OF THE FUNDED INVESTIGATORS WILL TALK ABOUT THAT AS WELL. AND THE WHOLE AFTERNOON WE'VE DEVOTED TO A REALLY IMPORTANT ISSUE THAT WE AT NCATS HAVE SPENT A GOOD PART OF THE LAST FIVE YEARS ON, WHICH IS THE PROBLEM OF HARMONIZED SINGLE CENTRAL INSTITUTIONAL REVIEW BOARD REVIEW FOR MULTI-SITE STUDIES. WHEN I BECAME NCATS DIRECTOR, THIS WAS BROUGHT TO ME BY EVERY POSSIBLE SOURCE FROM THE CTSA IPs THEMSELVES TO INVESTIGATORS AT OTHER INSTITUTES, PATIENT ADVOCATES WHO TRIED TO GET STUDIES GOING, TO PATIENTS WHO HAD GOTTEN STUCK TRYING TO ENROLL IN CLINICAL STUDIES FOR THEMSELVES OR THEIR CHILDREN, BECAUSE OF THESE DELAYS IN THIS PROCESS TO COLLEAGUES IN BIOTECH AND PHARMA WHO CONFRONT SOME OF THE SAME ISSUES WHEN WORKING WITH ACADEMIC INVESTIGATORS, SO I'M GLAD TO SAY THAT THIS HAS BEEN AN UNBRIDLED SUCCESS, AND ONE OF THE THINGS THAT FRANKLY I AM MOST PROUD OF WHAT NCATS HAS DONE IN THE LAST FIVE YEARS. PARTICULARLY I SUPPOSE FOR TWO REASONS. ONE, WHEN WE STARTED IT, EVERYONE WE TALKED TO, THOUGH THEY ALL AGREED IT WAS REALLY IMPORTANT, EVERYONE AGREED IT WAS IMPOSSIBLE. I WAS TOLD ON MORE THAN ONE OCCASION IF I COULD ACTUALLY GET NCATS TO SUCCEED IN DOING THIS THAT WOULD BE GROUNDS FOR CANONIZATION. I'M NOW AWAITING A LETTER FROM THE POPE THAT HAS YET TO ARRIVE BUT I KNOW IT'S JUST CAUGHT IN THE MAIL SOMEWHERE. [LAUGHTER] >> (INAUDIBLE). >> OH, I HAVE TO BE BEATIFIED. >> (INAUDIBLE). >> OH! AH, THIS IS REALLY PROMISING. OKAY. SO WE'LL HAVE TO ADD THAT TO THE COUNCIL SCHEDULE. >> DO NOT ENCOURAGE. [LAUGHTER] AND THE OTHER IS HOW IT HAPPENED. THAT IS, THIS WAS AN INCREDIBLE TEAM EFFORT, WHERE A LOT OF PEOPLE, MANY, MANY, MANY PEOPLE, PUT ASIDE WHAT WOULD ADVANCE THEIR OWN CAREERS TO DO SOMETHING THAT BENEFITED EVERYONE, BENEFITED PERHAPS NOT EVEN THEMSELVES AND THEIR CAREER BUT WOULD HUGELY MOVE FORWARD THE AGENDA OF GETTING MORE TREATMENTS TO MORE PATIENTS MORE QUICKLY. AND FOR THAT REASON, THE PRESENTATION THIS AFTERNOON IS A LITTLE ODD. WE DON'T HAVE ONE PERSON; WE ACTUALLY HAVE FIVE PEOPLE OR MAYBE EVEN MORE, A COUPLE PEOPLE FROM NCATS, PETRA KAUFFMAN AND MICHELE CULP, GORDON BERNARD AND THOSE FROM HARVARD AND WE'LL HAVE A PANEL DISCUSSION AFTER THAT. THAT PANEL DISCUSSION IS BOTH TO REFLECT ON HOW THIS HAPPENED, BECAUSE THERE ARE MANY OTHER THINGS THAT NCATS HAS IN FRONT OF IT THAT ARE SAID TO BE IMPOSSIBLE OR INTRACTABLE, SO WHAT CAN WE LEARN FROM WHY THIS WORKED? AND THEN SECONDLY, WHAT DO WE NEED TO DO TO BRING THIS TO ITS FULL PROMISE. THIS HAS COME A LONG WAY, BUT WE'RE JUST STARTING IMPLEMENTATION AND IT'S REALLY USEFUL FOR US TO HEAR FROM YOU ALL ABOUT WHAT YOU THINK THE PROBLEMS WILL BE. SO WE'LL CELEBRATE FOR THE FIRST HOUR AND THEN WE'LL CONSIDER THE CHALLENGES IN THE SECOND HOUR. AND THEN WE'LL ADJOURN THE OPEN SESSION AND THEN FOR THOSE INVOLVED WE WILL CONVENE THE CLOSED SESSION AFTER A SHORT BREAK. SO WITH THAT, I'M GOING TO TURN IT OVER TO ANNA WHO WILL BRIEFLY CONFIRM SOME LOGISTICS AND FUTURE MEETING DATES. >> THANK YOU, CHRIS. THE MINUTES FROM THE MAY 2017 MEETING ARE AVAILABLE IN YOUR ELECTRONIC COUNCIL BOOKS AND FOLDERS. MOTION TO APPROVE IN SECOND? ALL IN FAVOR? OPPOSED? ANY ABSTENTIONS? THE MINUTES ARE APPROVED. THERE ARE NO REMAINING JOINT MEETINGS IN 2017. IN 2018 THE JOINT MEETINGS WILL BE HELD IN BETHESDA ON JANUARY 11, MAY 10, SEPTEMBER 27, WHICH IS RATHER LATE. IN 2019 ON JANUARY 10, MAY 16, SEPTEMBER 19. THE CAN REVIEW BOARD VIRTUE VALUE MEETINGS ON DECEMBER 13 THIS YEAR, DECEMBER 14 IN 2018 AND ON DECEMBER 15 IN 2019. I'M SORRY? THE WAY I SAID IT IS THE CORRECT ORDER ACTUALLY. DECEMBER 13, 2017. DECEMBER 14, 2018, DECEMBER 15, 2019. AND WE'LL GO BACK AND CONFIRM, MAKE SURE THAT'S RIGHT. >> (INAUDIBLE). >> ABSOLUTELY. I WILL MAKE SURE EVERYBODY HAS THE ABSOLUTE CORRECT DATES. I'D LIKE TO TURN THE FLOOR OVER TO CHRIS, AND HE'S GOING TO GIVE THE DIRECTOR'S UPDATE. ONE OF THE THINGS THAT'S WONDERFUL ABOUT THIS GROUP IS SOME OF YOU ARE STILL NEW. YOU'RE SO NEW THE PAINT HASN'T EVEN DRIED ON YOU YET. THAT IS, THAT YOU'RE STILL AD HOC. SO I'M GOING TO GO THROUGH SOME THINGS THAT YOU WOULD KNOW IF SIX YEARS, BUT OF COURSE THE GREAT THING IS WE HAVE A WHOLE NEW CROP OF FOLKS WHO ARE GOING TO TAKE A FRESH LOOK AT THESE THINGS. AND SO I'M GOING TO GIVE YOU SOME BACKGROUND IN PARTICULAR PLACES THAT I THINK MIGHT BE USEFUL FOR ORIENTING. THE FIRST IS THAT WE DECIDED A COUPLE OF YEARS AGO TO GO FROM KILLING TREES AND GIVING YOU LARGE AMOUNTS OF PAPER ABOUT THE ACTIVITIES THAT NCATS HAS BEEN INVOLVED IN SINCE THE LAST COUNCIL MEETING, WHICH WE DID FOR THE FIRST FEW TO GIVING YOU AN ACTIVITY SUMMARY ON ONE OF THESE, ON A THUMB DRIVE, AND SO YOU HAVE EVERYTHING ELECTRONICALLY, FOR A NUMBER OF COUNCIL SESSIONS WE PRINTED THESE OUT IN ACTIVITY SUMMARY BOOKS. WE'RE CERTAINLY MORE THAN HAPPY TO DO THAT FOR ANY OF YOU WHO WOULD LIKE THESE, WE CREATE A SPIRAL-BOUND BOOK TO SEND YOU BEFORE THE COUNCIL IF YOU WANT TO LOOK AT IT ON THE PLANE OR WHAT HAVE YOU. ALL YOU HAVE TO DO IS LET ANNA KNOW AND WE'RE MORE THAN HAPPY TO DO THAT. BUT I HOPE YOU WILL LOOK AT THE ACTIVITY SUMMARIES, BECAUSE IT'S VERY HARD FOR ME TO SELECT THINGS EVERY TIME WE DO A COUNCIL, I LIKE TO GIVE YOU SOME IDEAS. SCIENCE THAT'S GOING ON, BUT IT'S VERY HARD FOR ME TO DO THAT, I FEEL LIKE I HAVE 100 CHILDREN HERE AND I CAN ONLY CHOOSE THREE TO TALK ABOUT EVERY MEETING. SO I HOPE YOU'LL LOOK AT ALL THE CHILDREN WHO ARE ON HERE. SO HERE'S THE AGENDA. WHAT I LIKE TO DO IN THESE MEETINGS IS TO GIVE YOU MOST IMPORTANTLY A SENSE OF WHERE THE SCIENCE IS GOING. I LIKE TO DO THIS TRUE TO OUR NAME, ADVANCING TRANSLATIONAL SCIENCES, SO WHAT HAVE WE DONE TO ADVANCE THE SCIENCE OF TRANSLATION SINCE I LAST TALKED TO YOU? SO -- AND I TEND TO BREAK THIS UP MOST TIMES BETWEEN EARLY STAGE, THAT IS AFTER FUNDAMENTAL RESEARCH, EARLY STAGE TRANSLATION, SORT OF MID-STAGE AND LATE STAGE CLINICAL, THIS TIME I'M GOING TO TALK TO YOU IN THE EARLY ONES ABOUT NEW WAYS TO ACCESS PREVIOUSLY INTRACTABLE TARGETS, ONE BEING NEW CHEMISTRY, ONE NEW MODALITIES, STEM CELLS. IN THE MIDDLE STAGE THAT IS ALMOST GETTING TO PEOPLE I'M GOING TO TALK ABOUT WHAT WE'RE DOING IN GENE THERAPY, AND THEN IN THE LATE STAGE TELL YOU A FEW THINGS ABOUT WHAT'S BEEN GOING ON IN THE CTSA PROGRAM, AND I'M GOING TO FOCUS ON ONE THING AS I OFTEN HAVE TO DO WITH ALL OF THESE PROGRAMS, I'M GOING TO TALK ABOUT COMMON METRICS, WHICH MAY SOUND REALLY DRY BUT I'M GOING TO TRY TO CONVINCE YOU THAT IT IS EXACTLY THE OPPOSITE, AND HAS BEEN REALLY A TRANSFORMATIONAL PROGRAM WHICH I WANT TO RECOGNIZE HARRY SELKER FOR, WHEREVER HE WENT, RIGHT THERE, WHO HAS BEEN VERY INVOLVED IN THIS FROM THE BEGINNING. AND I WILL GO THROUGH ADMINISTRATIVE POLICY AND BUDGET UPDATES WHICH I THINK YOU NEED TO KNOW AS A COUNCIL AT THE END AS WELL. OKAY. SO LET'S START OUT WITH THE NEW MODALITIES. I FEEL LIKE I'M TELLING A BEDTIME STORY HERE. ONCE UPON A TIME THERE WERE A GROUP OF INFECTIOUS ORGANISMS, AND THESE ARE REALLY NASTY BUGS. THEY CAUSE A NUMBER OF REALLY DEVASTATING TROPICAL DISEASES SUCH AS THESE ON THE SLIDE, AS WELL AS POTENTIALLY DEADLY BACTERIAL INFECTIONS, AMONG THEM STAPH AUREUS AND ANTHRAX. WHAT'S INTERESTING ABOUT THESE IS THEY ALL SHARE A UNIQUE VULNERABILITY, IT TURNS OUT, IN THE WAY THEY DO GLYCOLYSIS. THAT IS, THE WAY THEY GENERATE ATP, AND THIS HAS TO DO WITH A PARTICULAR STEP OF THE GLYCOLYTIC PATHWAY, SHOWN IN THE BOX HERE, ENZYMATICALLY FACILITATED BY AN ENZYME PHOSPHO-GLYECRATE MUTASE. IN PEOPLE THAT'S DEPENDENT ON CO-FACTORS. THE ACTIVITY WAS WELL, GOSH, THIS PRESENTS POTENTIALLY A WONDERFUL PHYLOGENETIC DIFFERENCE WHICH WOULD ALLOW US TO INTERDICT AN ESSENTIAL PATHWAY IN MICROBES AND PARASITES, BUT NOT HIT THE HUMAN BECAUSE THE HUMAN HAS A QUITE DIFFERENT MECHANISM OF THIS GLYCOLYSIS. WELCOME, FRANK. OKAY. SO THIS VERY PROMISING IDEA, HOWEVER, HAS RUN INTO THE SAME PROBLEM THAT PEOPLE WHO ARE INTERESTED IN NOVEL BIOLOGICAL SPACE RUN INTO VERY FREQUENTLY, WHICH IS THAT THE CHEMICAL SPACE THAT IS THE KINDS OF SMALL MOLECULES OR EVEN PROTEINS ANTIBODIES THAT CAN INTERDICT NOVEL PATHWAYS DOES NOT EXIST. IF ONE RUNS THESE PATHWAY ASSAYS ACROSS EXTANT CHEMICAL LIBRARIES ONE COMES UP WITH NOTHING. NO CHEMICALS, NO CHEMICAL DRUG LIKE STRUCTURES WHICH WOULD BE ABLE TO INHIBIT THIS OR RELATED KINDS OF ENZYMES. AND THERE WERE A NUMBER OF PUBLISHED EFFORTS FROM GENZME, NATIONAL CENTER FOR CENTER FOR DRUG SCREENING SHANGHAI, NONSTARTERS FROM A CHEMICAL POINT MUCH VIEW. THE NATURE OF THE SUBSTRATE AND PRODUCT ARE VERY UNUSUAL AND VERY DIFFICULT TO INTERDICT. NCATS HAS A REAL INTEREST IN EXPANDING CHEMICAL SPACE AND MODALITY SPACE. THIS WILL BE THE SUBJECT OF ONE OF THE CONCEPT CLEARANCES LATER THAT I'M MOST EXCITED ABOUT, AND YOU'LL HEAR ABOUT THAT AFTER THE BREAK. THIS IS A RELATED APPROACH EXPLORING NOVEL CHEMICAL MODALITIES, AND THIS, AS NCATS ALWAYS DOES, IS A COLLABORATION WHERE NCATS HAD SOME PARTICULAR EXPERTISE IN ASSAY DEVELOPMENT IN SCREENING. THIS CAME FROM NEW ENGLAND BIOLABS WHO IDENTIFIED THIS ENZYME TO BEGIN WITH AND FROM A PROFESSOR AT THE UNIVERSITY OF TOKYO WHO PIONEERED A NOVEL SO-CALLED MRNA CYCLIC PEPTIDE TECHNOLOGY WHICH ALLOWS THE CREATION OF LITERALLY TRILLIONS OF ESSENTIALLY LOCKED PEPTIDES, SO CALLED LARIAT PEPTIDES WHICH LOOK LIKE A NOOSE WHICH CONSTRAIN THE FORM OF ENZYMES AND ALLOWS THEM TO WORK BETTER AS POTENTIAL INSTRUCTION. AND THEN A STRUCTURAL BIOLOGIST AT THE UNIVERSITY OF KANSAS --& THIS IS JIM INGLAZE, AND THESE ARE FOLKS AT THE UNIVERSITY OF TOKYO. I PUT THEM IN THE SLIDES, THOSE OF YOU INTERESTED MIGHT BE ABLE TOFOLLOW UP ON THIS. THIS IS A VARIATION OF THE BROAD FIELD OF DNA ENCODED CHEMICAL LIBRARIES, ESSENTIALLY THIS IS A TECHNOLOGY BY WHICH AN mRNA LIBRARY THAT ENCODES TRILLIONS OF DIFFERENT AMINO ACIDS ARE LINKED TO BEADS, THOSE AMINO ACIDS OR mRNAs ARE REVERSE -- SORRY, LEAD TO TRANSCRIBED AND THEN INCUBATED WITH THE TARGET, mRNAs ARE AMPLIFIED BY PCR AND THERE BY THE PEPTIDE SEQUENCE IDENTIFIED, AND THEN LARGE AMOUNTS CAN BE PRODUCED USING SOLID PHASE PEPTIDE SYNTHESIS, A REITERATIVE PROCESS AS A NUMBER OF RELATED TECHNOLOGIES ARE. BUT THE IMPORTANT THING IS IT ALLOWS US TO GET INTO A CHEMICAL SPACE TOTALLY NOVEL AND VERY DIVERSE. SO SKIPPING THROUGH OF COURSE A YEAR OR TWO OF WORK, TRISH DRANCHAK IN JIM'S GROUP DID ALL OF THESE SCREENS AND IDENTIFIED A NUMBER OF PEPTIDES WHICH WERE INHIBITORY, WHAT YOU'RE LOOKING AT HERE IS THE PIC 50, YOU HAVE TO TAKE THE NUMBER, THAT IS THE NUMBER TO THE MINUS EXPONENT.& IC 50 IN THE CASE OF 9.6 IS 10 TO THE MINUS 9 IS ITS IC 50, SO VERY, VERY POTENT. THAT'S A STRUCTURE AT THE BOTTOM, QUITE A COMPLEX STRUCTURE, AS YOU CAN SEE. THEN WHAT THE GROUP DID IS OF COURSE -- WELL, NOT OF COURSE. WHAT THE GROUP DID BECAUSE OF JIM'S EXPERTISE IN THIS PARTICULAR AREA OF BIOCHEMICAL CATALYSIS DID SOME BEAUTIFUL CO-CRYSTAL STRUCTURES SHOWING THE ALLOSTEERIC MECHANISM, ALL IMPORTANT FOR ANALOG DEVELOPMENT NOW GOING ON BOTH IN PROFESSOR SUGA'S LAB IN TOKYO AND VIA THE NCATS MED CHEM TEAM TO ACHIEVE A BETTER ORGANISMAL UPTAKE AND DELIVERY AND MODEL ORGANISM USING C. ELEGANS AND NEMATODES THAT CAUSE DISEASE, COLLABORATION WITH MIKE CAPELLO AND, AND ANDY GOLDEN AT NINDS. EVERYTHING I TOLD YOU IS GENERIC. I COULD THROW YOU A DIFFERENT ENZYME AND DO EXACTLY THE SAME THING, EXACTLY WHAT NCATS LIKES TO DO. DEVELOP A TECHNOLOGY, HERE'S THE DEMONSTRATION, NO REASON TO BELIEVE IT'S A SPECIAL CASE. NOW THE QUESTION IS HOW DO WE DISSEMINATE THAT TECHNOLOGY? CLEARLY FINDING NEW FORMS OF CHEMICAL MATTER HAS BEEN DONE HERE, APPLICABLE TO ANY TARGET PROTEIN THAT CAN BE EXPRESSED AND PURIFIED, IMMOBILIZED RECEPTOR OR BINDER ON A SOLID FACE RESIN, AND THERE'S ALSO CONSIDERABLE ROOM TO INNOVATE ON THIS TECHNOLOGY, AND DISSEMINATE IT TO OTHERS WHO CAN USE IT. SO WE'RE REALLY EXCITED ABOUT THIS. IT'S ALL JUST BEEN PUBLISHED. AND WE LOOK FORWARD TO BOTH FURTHER EFFORTS ON THIS PARTICULAR PROTEIN WHICH REMEMBER IS A REALLY NASTY ACTOR, AND AS WELL AS FUTURE APPLICATIONS OF THIS KIND OF TECHNOLOGY. I'M GOING TO SWITCH GEARS AND TELL YOU ABOUT ANOTHER SLIGHTLY MORE ADVANCED KIND OF TECHNOLOGY TO GET TO NEW TARGETS, NEW INDICATIONS, AND THIS HAS TO DO WITH STEM CELLS. SO I THINK WE'RE ALL AWARE OF THE REALLY REMARKABLE ADVANCES THAT HAVE HAPPENED IN THE STEM CELL FIELD IN THE LAST 20 YEARS. PARTICULARLY AFTER THE CREATION, AFTER THE DISCOVERY OF THE MECHANISM TO CREATE INDUCED PLEURIPOTENT STEM CELLS BY YAMANAKA ABOUT A DECADE AGO NOW. AND -- BUT IF YOU THINK ABOUT THE PROMISE OF STEM CELLS ONE READS ABOUT, VERY FREQUENTLY IN THE SCIENTIFIC PRESS AND THE LAY PRESS, AND THEN YOU ASK YOURSELF, WELL, HOW MANY OF THESE HAVE YOU ACTUALLY READ ABOUT BEING USEFUL IN THE CLINIC? AND HOW MANY OF THEM HAVE YOU READ ABOUT CAUSING TUMORS PERHAPS OR CAUSING BAD OUTCOMES? AND AS IS VERY FREQUENT, IN FACT IS THE RULE IN TRANSLATION, THOSE TWO WORLDS ARE VERY FAR APART. THAT IS, THE FUNDAMENTAL DISCOVERY AND CLINICAL APPLICATIONS ARE VERY FAR APART. SO ABOUT THREE OR FOUR YEARS AGO WE WERE ASKED BY THE NIH COMMON FUND AND FRANCIS COLLINS SPECIFICALLY TO TAKE A LOOK AT THIS PROBLEM AND ASK WHY -- HAD -- WHERE IS THE TRANSLATIONAL PROBLEM? WHAT WE FOUND IS IN SOME WAYS SPECIFIC TO STEM CELLS, BUT IN SOME WAYS ALMOST DEPRESSINGLY SIMILAR AND FAMILIAR. THAT IS, THAT THE VERY DIFFICULT WORK TO GO FROM SOMETHING THAT CAN HAPPEN, WHICH HAS BEEN PUBLISHED, TO SOMETHING WHICH DOES HAPPEN AND CAN BE MADE TO HAPPEN REPRODUCIBLY WHICH OF COURSE IS WHAT ONE NEEDS TO GO TO THE FDA, MUCH LESS DO SOMETHING FOR A PATIENT, THAT HAD NOT BEEN DONE BECAUSE OF A LACK OF EXPERTISE, A LACK OF FUNDING, A LACK OF STRUCTURE, CULTURE, ALL THE THINGS WE TALK ABOUT AROUND THIS TABLE ALL THE TIME. AND THERE HAD BEEN A NUMBER OF RECORDS BY THE WELLCOME TRUST, BY THE AMERICAN SOCIETY FOR CELL BIOLOGY, BY THE CERN GROUP THERE CALIFORNIA TALKING ABOUT THIS. AND THE FACT THAT SOMEBODY REALLY OUGHT TO SOLVE THOSE PROBLEMS, ESSENTIALLY CMC PROBLEMS, DRUG PEOPLE, YOU KNOW WHAT I MEAN BY THIS. SO WE WERE THEN TASKED TO SOLVE THIS PROBLEM, WITH A $6 MILLION BUDGET AND DO IT IN FIVE YEARS. HOWEVER, NEVER SHRINKING FROM A GOOD CHALLENGE WE SAID OKAY, AND WE'VE TAKEN THIS ON NOW, THE COLLABORATIVE MODEL IS OUR USUAL NCATS TO DEVELOP AN INTERNAL TEAM WITH UNPRECEDENTED EXPERTISE IN THE SCIENCE OF STEM CELL TRANSLATION, BUT TO RELY ON THE VERY CLOSE COLLABORATION WORK EXTERNAL COMMUNITY, EXTRAMURAL AND INTRAMURAL, WHO ARE EXPERTS IN PARTICULAR KINDS OF CELL TYPES. I WANT TO EMPHASIZE WHAT WE'RE DOING IS NOT CREATING iPS CELLS. CREATING iPS CELLS IS STRAIGHTFORWARD, YOU CAN DO IT WITH A ROBOT NOW. THE QUESTION IS HOW DO YOU GO FROM IPC CELL THAT YOU HAVE TO CHARACTERIZING THAT iPS CELL, DEMONSTRATE IT'S PLEURIPOTENT, IT IS WHAT YOU SAY IT IS AND WHEN YOU DIFFERENTIATE TO A PARTICULAR CELL TYPE, WHETHER IT'S A RETINAL PIGMENT EPITHELIA OR CARDIOMYOCYTE, HOW CAN YOU DEMONSTRATE, WHAT ARE THE IMPURITIES, TO WHAT PERCENTAGE, ARE THEY GOING TO INTERFERE WITH THE MAJOR COMPONENT, ALL THE THINGS WE THINK ABOUT IN DEVELOPING ANY KIND OF THERAPEUTIC. THIS HAS TO OF COURSE BE DONE WITH INTERDISCIPLINARY TEAMS, IT'S ONE OF THE REASONS THIS HAS NOT BEEN DONE BEFORE, AGAIN IT'S KIND OF A CLASSIC SITUATION THAT WE RUN INTO, ACADEMIC INVESTIGATORS HAVE DIFFERENT INCENTIVES AND DIFFERENT KINDS OF OPERATIONAL STRUCTURES, COMPANIES HAVE TRIED TO GET INTO THIS SPACE BUT PROBLEMS ARE SO DAUNTING ALL THE STEM CELL COMPANIES HAVE GOTTEN OUT OF THAT SPACE. GERON WAS THE ORIGINAL COMPANY, THEY GOT OUT OF THE STEM CELL BUSINESS AND BOUGHT CANCER KINASE INHIBITORS, THEY ARE NOW A CANCER KINASE COMPANY. THAT WAS A VERY REASONABLE BUSINESS DECISION BECAUSE OF THE DISTANCE TO COMMERCIAL APPLICATION. AND WE ALSO ARE DEVOTED AROUND HERE TO THE IDEA THAT ONE TECHNOLOGY IS NEVER GOING TO BE THE SILVER BULLET TO AN. YOU HAVE TO TRIANGULATE WITH MULTIPLE TECHNOLOGIES TO SOLVE THESE PROBLEMS. THIS IS A PICTURES OF STEM CELLS FROM THE LAB WITH NEURITES, THIS IS ILYAS SINGEC WHO RUNS THE PROGRAM. YOU'LL MEET HIM AT SOME POINT. HE DID STEM CELL WORK IN GERMANY THEN AT THE INSTITUTE IN LA JOLLA AND THEN THE STEM CELL GROUP AT PFIZER BEFORE COMING HERE. THE PURPOSE IS TO ESTABLISH QQ STANDARDS TO DEFINE PLURIPOTENCY AND DIFFERENTIAL THE CELL TYPES. IT'S COMPLICATED. DIFFERENTIATE, USE AN ANTIBODY, SAY STAINS WITH A HEPATOCYTE MARKER OR NEURAL MARKER, THEREFORE IT'S A NEURON. NO, IT MEANS IT STAINS WITH THAT ANTIBODY MARKER. THAT'S ALL IT MEANS. NO MORE, NO LESS. DO WE NEED TO DO THIS VIA TRANSCRIPTOMES OR PROTEOMES OR METABOLOMES OR A SERIES OF SURFACE MARKERS, SOME COMBINATION THEREOF, HOW DO WE DO THAT? DEVELOP METHODS TO ASSESS HETEROGENEITY. ONE OF THE THINGS THAT WE AND EVERYONE ELSE RUNS INTO IS THAT WE LOVE TO HAVE BIG LAWNS OF UNIFORM CELLS, BUT REAL CELLS DON'T LIKE THAT. THEY ARE CONSTANTLY TELLING EACH OTHER WHAT TO DO. THEY ARE KIND OF LIKE PEOPLE THAT WAY. AND THEY ARE CONSTANTLY SAYING I'M ALREADY CELL TYPE A, YOU GOT TO BECOME CELL TYPE B AND THEY HAVE ARGUMENTS THROUGH NOTCH AND DELTA AND FINALLY COME TO AGREEMENT ON WHO IS GOING TO BE WHAT. BUT WHAT THAT MEANS IS WHEN YOU DO THESE KINDS OF EXPERIMENTS, IT'S VERY HARD TO GROW UP, IT'S NOT LIKE GROWING UP A KILOGRAM OF AN API WHERE YOU CONTROL THE REACTION. THESE ARE BIOLOGICAL ORGANISMS AND THEY HAVE THEIR OWN WILL, IF YOU WILL. THEY HAVE THEIR OWN AGENDAS, AND SOME OF THAT IS FAIRLY STOCHASTIC. THE QUESTION IS HOW DO WE DEAL WITH THAT HETEROGENEITY? JUST IMAGINE IF YOU WERE DEVELOPING A SMALL MOLECULE, FOR WHATEVER REASON IT WAS IMPOSSIBLE TO GET MORE THAN 50 PER CENT PURITY OF YOUR COMPOUNDS BECAUSE COMPOUNDS HAVE MINDS OF THEIR OWN. HOW WOULD YOU DEAL WITH THAT IF YOU WANT TOP GET TO THE CLINIC? REALLY INTERESTING QUESTIONS. IS THERE SOME WAY TO GET AROUND THAT OR NOT? THEN ONCE WE GET TO THAT POINT, DEVELOP STANDARDIZE METHODS TO PRODUCE MATURE CELLS THAT ACTUALLY MEET THOSE STANDARDS THAT WE'VE ESTABLISHED, AND THEN AFTER THAT OR SOMETIMES IN PARALLEL TO DISCOVER, VALIDATE AND DISSEMINATE, THE 3-Ds, DISCOVERY, DEMONSTRATE AND DISSEMINATE, SMALL MOLECULE REAGENTS TO REPLACE THE EXPENSIVE RECOMBINANT PROTEINS, XENOGENIC MATERIAL, FETAL BOVINE. WHEN I WAS FIRST DOING THIS, STILL USED TODAY, SOMETHING CALLED CHICKEN EMBRYO EXTRACT THAT YOU USE TO MAKE THESE CELLS DIFFERENTIATE. AND LITERALLY WHAT ONE DOES IS ONE HAS A NUMBER OF CHICKEN EGGS, SO THAT ONE LETS GROW UP TO A CERTAIN AGE, PUT THE EMBRYOS THERE A WARING BLENDER AND EXTRACT THEM, GRIND THEM UP AND POUR THAT STUFF ON THE CELLS AND IT MAKES THEM DIFFERENTIATE. NOW, IMAGINE YOU GO TO FDA, AND YOU SAY THIS IS THE WAY WE'RE MAKING OUR CELLS. THEY WOULD PROBABLY HAVE A STROKE. AND WOULD THROW YOU OUT OF THE ROOM, RIGHTLY SO, BECAUSE IT'S COMPLETELY UNDEFINED. BUT THAT'S THE STATE OF THE ART. AND IT WORKS, IF YOU'RE TRYING TO DEMONSTRATE THE CAPACITY OF SOMETHING TO HAPPEN. IT'S NOTHING WRONG WITH THAT. BUT IT'S DIFFERENT FROM WHAT WE'RE TRYING TO DO. IT'S A TRANSLATIONAL PROBLEM. THE OTHER THING THAT WE RUN INTO ALL THE TIME IS THE TIME AND EFFORT REQUIRED TO MAKE THESE CELLS IS COMPLETELY IMPRACTICAL. THE AVERAGE DIFFERENTIATION PROTOCOL THAT WE RUN INTO AROUND 6 MONTHS TO MAKE A SINGLE BATCH OF CELLS TO USE POTENTIALLY FOR A SINGLE PATIENT. AND IT GOES THROUGH 10 OR 15 DIFFERENT STEPS, MULTIPLE DIFFERENT MEDIA AND ALL KINDS OF THINGS. SO THE QUESTION IS HOW TO DO THIS, HOW DO INDUSTRIALIZE THAT IS REALLY THE QUESTION. SO, THE REASON I'M TELLING YOU ABOUT THIS PARTICULARLY AT THIS POINT IS, NUMBER ONE, BECAUSE I HAVEN'T TOLD YOU ABOUT IT BEFORE BUT THE OTHER IS THAT WE HAD OUR GRAND OPENING OF THE LAB JUST ABOUT TWO MONTHS AGO. IT IS ABOUT THE -- IT IS MY NEW FAVORITE LAB. THIS LAB HAS EVERY ADVANCE TOY YOU CAN POSSIBLY MANAGE. AS YOU KNOW, THOSE WHO KNOW ME KNOW I'M A TOY GUY. I AM AN AN UNABASHED TECHNOPHILE BECAUSE OF THE THINGS NEW TOYS ALLOW YOU TO DO. ONE OF MY FAVORITE HERE IS A MACHINE THAT ALLOWS YOU TO DO SINGLE CELL PROTEOMICS. THAT IS CHARACTERIZED A LARGE AMOUNT OF PROTEOME IN A SINGLE CELL. JUST INCREDIBLE STUFF. AND THESE ARE THE FOLKS, ANTON THE SCIENTIFIC DIRECTORY. PINAR WHO RUNS THE LAB, SHE'S THE LAB MANAGER, AND ILYUS. SO WE'RE CUTTING THE PURPLE RIBBON HERE. AND I DON'T WANT YOU TO GO THROUGH ALL OF THIS BUT I WANT TO SHOW YOU ONE OF THE THINGS THAT WE'VE BEEN DOING, ILYUS AND THE GROUP HAS BEEN DOING, EXAMPLE OF WHAT WE WANT TO DO, IS TO AUTOMATE THESE KINDS OF PROCESSES. THIS IS A FULLY AUTOMATED AND EFFICIENT HEPATOCYTE DIFFERENTIATION THAT DOES CELL CULTURE AND SPLITTING BY ITSELF. WE DON'T NEED TO TOUCH THESE FOR THREE WEEKS, IT BURPS OUT HEPATOCYTES AT THE END THAT DO ALL THE THINGS HEPATOCYTES ARE SUPPOSED TO DO AND YOU CAN SEE THIS BY RPTCR AND PROTEIN HERE. LAST THING I WANT TO MENTION IS THAT NOW THAT WE HAVE THIS CAPACITY IN PLACE, WE'RE DOING WHAT WE ALWAYS DO, WHICH IS TO REACH OUT TO THE COMMUNITY BROADLY AND SAY, OKAY, HERE IS THIS WONDERFUL TECHNOLOGY, PLEASE BRING US YOUR PROBLEMS. BRING US DIFFERENTIATION PROBLEMS WHICH HAVE YOU STUCK. AND WE WILL CHOOSE THOSE ON THE BASIS OF BOTH DIVERSITY OF CELL TYPES AND WHETHER WE THINK IT'S TRACTABLE, CERTAINLY, BUT ALSO WHETHER WE THINK THE PARTICULAR PROJECT IS GOING TO TELL US SOMETHING GENERAL WE CAN APPLY TO OTHER PROJECTS. SO THOSE OF YOU WHO WERE IN THIS BUSINESS, I HOPE YOU WILL TAKE THESE SLIDES OR GOOGLE THIS BECAUSE WE'RE LOOKING FOR PROPOSALS RIGHT NOW. OKAY. SO THAT'S THE EARLY STAGE. MID-STAGE, WHAT WE'RE DOING HERE IS SOMEWHAT ALONG THE SAME THEME. THAT IS THAT CERTAINLY WE'RE INTERESTED IN NOVEL KINDS OF CHEMISTRY. CERTAINLY WE'RE INTERESTED IN NOVEL KINDS OF CELLULAR THERAPIES. BUT WE'RE ALSO INTERESTED IN GENE THERAPY. NOW, GENE THERAPY OF COURSE HAS A LONG HISTORY, NOT AS LONG AS SMALL MOLECULES BUT LONGER THAN STEM CELLS, BUT HAS MUCH THE SAME PROBLEMS THAT I DESCRIBED TO YOU IN THE STEM CELL PORTION. SOME OF THOSE PROBLEMS HAVE BEEN ADDRESSED AFTER THE GELSINGER INCIDENT A COUPLE DECADES AGO. THE COMMUNITY HAD A BIT OF AN "OH NO" MOMENT WHERE THEY GOT AHEAD OF THEMSELVES AND HAD TO DO TRANSLATIONAL WORK. SOME OF THAT HAPPENED. AS A RESULT THERE'S BEEN A RESURGENCE OF INTEREST IN GENE THERAPY THAT IS REPLACING DEFECTIVE GENES OR PUTTING EXOGENOUS GENES INTO CELLS FOR THE FIRST TIME, AND SO THERE ARE MANY, MANY GENE THERAPY PRODUCTS IN DEVELOPMENT. I SHOULD SAY THAT FOR THIS CALCULATION, AND FOR MOST CALCULATIONS, THAT INCLUDES CAR T AND THINGS LIKE IT. SO YOU MAY HAVE SEEN THERE WAS A BIG HEADLINE LAST WEEK ABOUT NOVARTIS, THE HEADLINE WAS FIRST GENE THERAPY APPROVED. NOW, THAT IS NOT GENE THERAPY, TO ME. THAT IS CELL THERAPY OF AN EX VIVO TRANSDUCED CELL THAT'S THEN GIVEN BACK TO THE PATIENT. QUIBBLING ABOUT TERMINOLOGY HERE BUT THERE'S A DIFFERENCE IN OUR VIEW WE HAVE TO KEEP STRAIGHT BETWEEN EX VIVO WHERE THE YOU TAKE THE CELLS OUT, TAKE SOMETHING OUT OR PUT SOMETHING IN THAT THE PATIENT EITHER DOESN'T NEED OR NEEDS TO HAVE, AND THEN PUT THE CELLS BACK, BACK IN AGAIN. CAR T OR CHIMERIC ANTIGEN RECEPTOR TECHNOLOGY, FOR CANCER, IS AN EXAMPLE OF THE FORMER. WHAT WE'RE TALKING ABOUT IS MAINLY THE LATTER. THAT IS THE USE OF A VECTOR, OFTEN A VIRUS, CARRYING A GENE TO A TISSUE IN THE PERSON. IN VIVO GENE THERAPY IS WHAT WE'RE MAINLY GOING TO TALK ABOUT HERE. SO THE CHALLENGES ARE MANY. AND THEY WILL LOOK FAMILIAR TO YOU. HOW DO YOU GET THE RIGHT DOSE TO THE RIGHT TARGET? HOW DO UP SCALE UP THESE THINGS IN A WAY THAT LIKE THE STEM CELLS GIVES YOU WHAT YOU NEED TO HAVE AND GIVES YOU WHAT FDA HAS TO HAVE. THE ONGOING PROBLEM OF IMMUNE RESPONSE TO THESE VECTORS, BECAUSE THEY ARE VIABLE VECTORS, LONG TERM SAFETY ISSUES AND OF COURSE COST, IT'S INTERESTING TO THINK THAT THE FIRST GENE THERAPY FOR LIPOPROTEIN LIPASE IN THE E.U. IS OFF THE MARKET BECAUSE AT A MILLION DOLLARS A POP THEY GOT SO FEW TAKERS THE COMPANY STOPPED MAKING IT. SO WE NEED TO BE CAREFUL THAT WE DON'T CELEBRATE PREMATURELY BECAUSE THESE PATIENTS ARE NOT BENEFITING BECAUSE THE GENE THERAPY IS NOW OFF THE MARKET. SO, A PARTICULAR PART, DIFFERENT PROGRAM WITHIN NCATS CALLED THERAPEUTICS FOR RARE OR NEGLECTED DISEASES HAS WORKED WITH THE FOLKS IN THE DIVISION OF CLINICAL INNOVATION, PETRA KAUFFMAN AND ANN PARISSER AND P.J. BROOKS AS WELL IN THE RARE DISEASE GROUP TO ESTABLISH A DIVERSE PORTFOLIO GENE THERAPY PROJECTS AS WE SOMETIMES SAY, POKE THE SKUNK, THAT IS WE TAKE ON PROBLEMS WHICH ARE REALLY HARD WHICH THE PRIVATE SECTOR CAN'T DO, DOESN'T WANT TO DO BECAUSE IT'S TOO RISKY. IN ORDER TO DE-RISK THEM. AND SOME OF THE TECHNOLOGIES UNDER DEVELOPMENT HAVE TO DO WITH MANUFACTURING, THE IDEA BEING A PLUG-AND-PLAY PLATFORM, MANUFACTURING PROCESS FOR AAV, COMPENDIUM OF STANDARD ANALYTICAL METHODS, HOW TO DO SELF SUSPENSION AND POTENTIATION, THINGS ONE LAST TO DO IN THIS SPACE. AND THEN DEVICES FOR CNS DELIVERY IN INFANTS OR NEWBORNS, I'LL SHOW YOU THIS IN A SECOND. WHAT I MEAN BY THE PLUG-AND-PLAY, A SENSE OF ONE MUCH THESE, WHAT'S BEEN HAPPENING SO FAR IS PEOPLE TAKE INDIVIDUAL VECTORS AND THEY TAKE THEIR GENE OF INTEREST AND PUT THAT INTO THE VECTOR, AND THEN WHEN ONE GIVERS GIVES THAT IT'S A COMBINATION THERAPY, THE VECTOR, ALSO THE GENE THEY ARE GETTING. WHEN SOMETHING HAPPENS IT'S HARD TO TELL WHAT IS DUE TO WHAT. EVERY TIME THE FDA HAS TO EVALUATE BOTH. AND SO IT OCCURRED TO US THAT, WELL, GOSH, YOU KNOW, THIS REALLY OUGHT TO BE LIKE TAKING YOUR CARRY-ON ONTO AN AIRPLANE. EVERY TIME YOU WANT TO TAKE A CARRY-ON ONTO AN AIRPLANE, YOU DON'T WANT TO HAVE TO MAKE A SUITCASE. BECAUSE THAT IS GOING TO DRIVE THE T.S.A. CRAZY. SO YOU COULD DO IT BUT IT'S GOING TO TAKE A LOT LONGER, YOU'RE GOING TO GET STOPPED BY THE T.S.A., THEY ARE GOING TO SERVE EVERYTHING. WOULDN'T IT BE GREAT IF YOU HAVE STANDARD SUITCASES THAT MEET T.S.A. REQUIREMENTS? AND IN FACT COMPANIES HAVE DONE THAT. NOW WE PROBABLY ALL HAVE ONE OF THOSE. AND WE KNOW WE CAN -- THEY ARE GOING TO BE CONCERNED ABOUT WHAT'S IN THE SUITCASE, RIGHT? BUT THEY ARE NOT CONCERNED ABOUT THE SUITCASE BECAUSE THEY HAVE SEEN IT A MILLION TIMES. THAT'S THE IDEA. CREATE A NUMBER MUCH SUITCASES, SMALL, MEDIUM, LARGE, THAT THEN COMPANIES WILL BE ABLE TO USE, AND THEN FDA KNOW ALSO THE SUITCASES AND CAN WORRY JUST ABOUT WHAT'S IN THE SUITCASES, WHAT'S THE GENE BEING TRANSDUCED. OKAY. LET ME GIVE AN EXAMPLE HERE. THE CASE STUDY HERE IS A RARE DISEASE AROMATIC H-AMINO ACID DECARBOXYLASE DEFICIENCY, VERY RARE DISORDER OF PROFOUND DEVELOPMENTAL FAILURE. THIS IS A CHILD ON THE RIGHT WHO I'LL SHOW YOU IN A MINUTE MORE DETAIL ON, SEIZURES, LIFE-LONG CARE, SEVERE FORMS HAVE A REALLY CATASTROPHIC COURSE AND DIE BEFORE THEIR TENTH BIRTHDAY. THOUGH IT IS RARE, IT'S CERTAINLY UNDERDIAGNOSED, AND COULD HAVE A PREVALENCE AS HIGH GLOBALLY OR 5,000 OR 6,000 PATIENTS. UNDOUBTEDLY DIAGNOSED DIFFERENT TIMES AS CEREBRAL PALSY, SEIZURE DISORDERS, ET CETERA. WHY DID WE TAKE THIS ON? WELL, AGAIN WE'RE TRYING TO DEVELOP GENERAL PRINCIPLES. SO IT TURNS OUT THAT THE GENE INVOLVED HERE IS VERY WELL KNOWN. IT'S IN THE DOPAMINE NOREPINEPHRINE PATHWAY. THERE'S A POSITRON EMISSION TECHNOLOGY LOOKING FOR DOPAMINE SYNTHESIS IN CONTAINMENT, PART OF THE BRAIN WHERE IT'S PARTICULARLY AFFECTED IN THIS DISORDER. ONE HAS A GOOD BIOMARKER TO ASSESS WHETHER THE GENE IS WORKING TO IDENTIFY PATIENTS FOR CLINICAL TRIALS IS QUITE STRAIGHTFORWARD, MONITORIG THERAPY IS QUITE STRAIGHTFORWARD, AND SO THAT'S WHY WE DECIDED TO TAKE THIS ON. A NUMBER OF THINGS HAD BEEN TAKEN CARE OF SO WE CAN FOCUS ON THE TECHNICAL PROBLEMS I MENTIONED. SO I'M NOT GOING THROUGH ALL OF THESE DATA OF COURSE BUT I WANT TO GIVE YOU A SENSE HOW THIS WORKS. THIS WAS A COLLABORATION AGAIN AS NCATS PROJECTS ALWAYS ARE BETWEEN THE NATIONAL UNIVERSITY IN TAIWAN, AND START-UP COMPANY CALLED AGILIS BIOTHERAPEUTICS. THE INTERVENTION HERE IS A SINGLE DOSE SO-CALLED AAV ADENOASSOCIATED VECTOR CARRYING HUMAN AADC GENE. THAT'S WHAT THAT MEANS, INTO THE BRAIN, THE PUTAMEN, THIS PART DEEP IN THE BRAIN. THE CHALLENGES WERE A NUMBER. THERE'S AN ULTRA RARE DISEASE, WE NEED TO DEVELOP A MECHANISM FOR STEREO TACTIC DELIVERY IN INFANTS, REGULATORY ISSUES, BUT WHAT WAS PARTICULARLY PROMISING IS THAT A NUMBER OF PATIENTS, 18 ACTUALLY, RECEIVED GENE THERAPY IN TAIWAN WITH SOME REMARKABLE CLINICAL RESPONSES WHICH I'LL SHOW YOU IN A SECOND. SO THIS COLLABORATION STARTED ABOUT A YEAR AGO, YEAR-AND-A-HALF AGO, TO CREATE GMP GRADE MANUFACTURING MATERIAL, DO ALL THE GOP ANIMAL WORK, BIODISTRIBUTION, PATIENT FINDINGS, EPIDEMIOLOGY, NATURAL HISTORY, WORKING ON DEVICE DEVELOPMENT FOR DELIVERY TO INFANT BRAINS. THE GOOD NEWS AND WHY I'M TELLING YOU ABOUT THIS AT THIS POINT, THERE WAS A VERY IMPORTANT REGULATORY MILESTONE ACHIEVED THIS SUMMER, AND END OF PHASE MEETING IN THE SUMMER WITH FDA COLLEAGUES WHERE THEY DECIDED THAT NO ADDITIONAL CLINICAL STUDIES WOULD BE NEEDED IN ORDER TO FIND A BLA NEXT YEAR. SO THIS IS CURRENTLY THE MOST ADVANCED CNS GENE THERAPY IN DEVELOPMENT. AND WE THINK IF THIS SUCCEEDS, IT WILL NOT ONLY ESTABLISH A MECHANISM BY WHICH OTHER CAN FOLLOW BUT NOW ESTABLISH A REGULATORY MECHANISM THAT OTHERS CAN FOLLOW AS WELL. SO I WANT TO SHOW YOU THIS BECAUSE WE TALK A LOT ABOUT HYPOTHETICALS AND GENERAL PROBLEMS, ET CETERA, ET CETERA. BUT WE AROUND HERE I KNOW LIKE ALL OF YOU THINK EVERY DAY ABOUT PEOPLE WHO MIGHT BENEFIT FROM THIS TECHNOLOGY, SO I WANT TO SHOW YOU THIS. THIS IS THE CHILD, THE PICTURE OF WHICH I SHOWED YOU BEFORE. THIS IS HER WHEN 4 YEARS OLD, HER MOM IS SHOWING HER A BALL AND STRING AND YOU SEE SHE'S REALLY MINIMALLY RESPONSIVE, REACTS A LITTLE BIT BUT DOESN'T MOVE SPONTANEOUSLY, IS REALLY MINIMALLY, MINIMALLY REACTIVE. SO SHE GOT THE GENE THERAPY AT THIS POINT. THIS IS HER A YEAR LATER. NOW, IT IS FORMALLY POSSIBLE THIS IS A SPONTANEOUS REMISSION. CERTAINLY FORMALLY POSSIBLE. NEVER BEEN SEEN. WOULD STRETCH THE IMAGINATION. BUT THIS IS WHAT CLINICAL TRIALS ARE FOR. AND THEN A YEAR LATER, THIS IS HER PLAYING WITH HER MOM. IF ALL I DID WAS SHOW YOU THIS, YOU WOULD BE HARD PRESSED TO SAY THIS KID HAS ANYTHING WRONG WITH HER. THIS IS THE SAME KID WHO TWO YEARS EARLIER WAS SITTING IN THE HIGH CHAIR. SO THIS IS INCREDIBLE. JUST INCREDIBLE. AND IF WE CAN MAKE THIS HAPPEN, WHAT A HUGE ADVANCE THIS WOULD BE, THIS APPROVAL OF THIS GENE THERAPY. OKAY. SO WE'VE ALSO SPENT A LOT OF TIME ASKING WHY DID THIS WORK? THE PROJECT, I MEAN. WHY DID THE PROJECT WORK? IT'S AGAIN SOMETHING THAT YOU WILL HEAR AROUND HERE ALL THE TIME BUT IT BEARS REITERATION BECAUSE IT IS SO UNUSUAL I'M AFRAID, STILL, THAT IS THERE ARE CLEAR STRENGTHS OF A PLATFORM, OF EXPERIENCED TEAM WITH DIVERSE EXPERTISE. USUALLY THESE ARE PUBLIC/PRIVATE PARTNERSHIPS WITH PATIENT ADVOCACY GROUPS DEEPLY INVOLVED. WE WORK ALMOST EXCLUSIVELY ON TRULY UNMET MEDICAL NEEDS, BUT WE'RE STARTING OUT WITH WELL UNDERSTOOD DISEASES WITH BIOMARKERS IN ORDER TO GET THE TECHNOLOGIES WORKED OUT. WITH LEARNINGS THAT CAN BE APPLIED TO MORE DIFFICULT TARGETS. SO I WANT TO EMPHASIZE THAT, AGAIN, THE KEY SUCCESS FACTORS OF THE BOTTOM ARE THE TEAM, PATIENT-FOCUSED AND INVOLVED DISEASE UNDERSTANDING AND PROGRAM, AND THE PUBLIC/PRIVATE PARTNERSHIPS HAVE REALLY BEEN KEY. ONE OTHER THING IN THE MID, I JUST WANT TO TELL YOU ABOUT, IS AN UPDATE BECAUSE A NUMBER OF YOU KNOW ABOUT THIS. A PREVIOUS TRND PROJECT, ONE OF THE ONES WE STARTED FIVE YEARS AGO, HAS REACHED ITS PUBLICATION. THIS IS A PROJECT THAT GRADUATED FROM TRND ABOUT 2 YEARS AGO, BUT -- AND IS NOW IN PHASE 3 TRIALS WITH THE COMPANY THAT ADOPTED IT. I WANTED TO SHOW YOU PHASE 1-2 THAT TRND HELPED SPONSOR AND FUND ON ANOTHER DEVASTATING NEURODEGENERATIVE DISEASE IN CHILDREN. NIEMANN-PICK DISEASE. THIS IS AN ENORMOUS TEAM EFFORT. THE AUTHORS AND ACKNOWLEDGMENTS IN THIS PAPER GO ON FOR SEVERAL PAGES, BUT THESE ARE VERY DIVERSE GROUPS AND MANY DIFFERENT PATIENT GROUPS, PATIENTS AND THEIR FAMILIES WHO HAVE PARTICIPATED IN THIS AND BEEN ACTIVE PARTNERS IN THIS FROM THE VERY BEGINNING. BUT WHAT I WANT TO DRAW YOUR ATTENTION TO IS THIS GRAPH, LOOKING, COMPARED TO HISTORICAL CONTROLS IN THIS CASE, THERE'S ABOUT A 70% DECREASE IN PROGRESSION IN THESE CHILDREN. AND THIS, AGAIN, IS A DISORDER WITH NO FDA-APPROVED THERAPY. SO ANOTHER EXAMPLE OF HOW THIS MODEL WHICH I JUST TOLD YOU ABOUT REALLY CAN DO REMARKABLE THINGS. OKAY. SO I'M GOING TO SWITCH GEARS NOW AND TELL YOU SOME EXAMPLES FROM THE CTSA PROGRAM, SO I'M GOING TO TALK ABOUT LATE NOW AND DO WHAT I'VE DONE IN PREVIOUS, GIVE YOU A GENERAL SENSE OF WHERE WE'RE GOING, WHAT'S THE PURPOSE OF THESE PROGRAMS AND GIVE YOU ONE PARTICULAR SNIPPET OF WHAT THIS PROJECT, WHAT THIS PROGRAM HAS DONE, LIKE I'VE DONE WITH THE OTHERS. SO THIS IS A VERY LARGE PROGRAM, AND IT'S MADE UP ESSENTIALLY OF TWO COMPONENTS, THERE ARE PROGRAM HUBS THAT INNOVATE LOCALLY, LOCAL INSTITUTION, AND COLLABORATE REGIONALLY WITH THE OTHER CTSA ORGANIZATIONS AS WELL AS NATIONALLY. AND PARTIALLY THROUGH THE WORK THAT THIS COUNCIL DID AND I'LL SHOW YOU THIS IN A SECOND, WE'VE ESTABLISHED -- WELL, ALSO BECAUSE OF THE P.I.s AND THE NEEDS OF THE FIELD, THERE'S PARTICULAR EMPHASIS ON THESE AREAS IN THE BOXES IN INFORMATICS TRAINING, STREAMLINING PROCESSES IN THE CLINICAL SPACE, COMMUNITY ENGAGEMENT, AND UNDERSTUDIED POPULATIONS, AND THEN BELOW THERE ARE A NUMBER OF CROSS CTSA, CROSS-HUB INITIATIVES THAT LEVERAGE THESE STRENGTHS TO SOLVE THE SYSTEMATIC PROBLEMS THAT DOESN'T MATTER WHETHER YOU'RE IN INDIANAPOLIS IN HARRY'S CASE IN BOSTON, OR SAN FRANCISCO, ALL THE SAME PROBLEMS, HOW DO WE LEVERAGE ENORMOUS EXPERTISE AT THESE PLACES TO SPREAD THE WEALTH, TO ALLOW THESE ORGANIZATIONS TO DEVELOP NEW SOLUTIONS, DEMONSTRATE THEIR UTILITY AND THEN DISSEMINATE THEM. THERE'S A NUMBER OF THINGS GOING ON HERE, DOMAIN TASK FORCES, COLLABORATIVE INNOVATION AWARDS, THOSE OF YOU INVOLVED IN CLOSED SESSION WILL HEAR ABOUT. THESE ARE AWARDS WHERE THREE OR MORE CTSAs WORK TOGETHER TO SOLVE A PARTICULAR PROBLEM IN THE TRANSLATIONAL SPACE OR TAKE A PROBLEM THAT'S BEEN ADDRESSED EFFECTIVELY AT ONE PLACE AND SEE IF IT CAN BE DISSEMINATED TO OTHERS. TRIAL INNOVATION NETWORK THAT YOU HEARD ABOUT AT LAST COUNCIL, CLINICAL DATA TO HEALTH INITIATIVE THAT YOU'LL BE HEARING ABOUT FROM KEN GERSING AND WHAT I TALK ABOUT TODAY, COMMON METRICS INITIATIVE. WHERE DID THIS -- OH. I JUST WANT TO REMIND YOU THIS ISES FOR -- THESE ARE SLIDES FOR THOSE ALMOST ALL OF YOU EXCEPT FOR A FEW ARE NEW SO I WANTED TO SHOW THESE. THESE ARE SLIDES I FREQUENTLY SHOW WHEN I TALK ABOUT NCATS, ABOUT THE PROBLEMS THAT NCATS ADDRESSES, IF YOU THINK ABOUT THE DISEASE THAT NCATS HAS AND THE PATIENT BEING THE TRANSLATIONAL PROCESS. THE PATIENT IS TRANSLATIONAL FAILURE. WHAT IS THE PROBLEMNESS OF THAT PATIENT IN THESE ARE THE PROBLEMS WE WORK ON, THAT BEDEVIL ANY TRANSLATIONAL PROJECT, NO MATTER WHAT THE DISEASE IS. AND THE CTSA PROGRAM DEALS SOME WHAP WITH THESE, BUT THIS IS MAINLY THE PRE-CLINICAL PART WHICH I'VE BEEN TELLING YOU ABOUT UNTIL THIS POINT. CTSA DEALS WITH ALL THESE DIFFICULT PROBLEMS, AND YOU'RE GOING TO HEAR ABOUT THE HARMONIZED IRBs HERE LATER, BUT THE OTHER THINGS WITH THE CTSA, THESE ARE MORE ORGANIZATIONAL CULTURAL ISSUES, IP MANAGEMENT, DATA TRANSPARENCY, PROJECT MANAGEMENT, HOW DO YOU GIVE CREDIT FOR TEAM SCIENCE, PROMOTION AND TENURE SYSTEM GOOD AT DOING OTHER THINGS BUT TEAM SCIENCE OFTEN DOESN'T DO WELL. HOW DO YOU GET CREDIT FOR HEALTH IMPROVEMENTS AS OPPOSED TO PUBLICATION? EDUCATION AND TRAINING, WHICH ARE TRANSLATIONAL SPECIFIC, AND NOVEL COLLABORATIVE STRUCTURES. OKAY. SO I WANT TO PUT THE COMMON METRICS INTO PERSPECTIVE AND WHERE THIS STARTED. SO BEFORE ALL OF YOU WERE PART OF THE COUNCIL, THERE WAS AN IOM REPORT ON THE CTSA PROBLEM IN 2013. THESE ARE SEVEN RECOMMENDATIONS. I WANT TO BRING YOUR ATTENTION TO THIS ONE, FORMALIZE AND STANDARDIZE CLEAR CONSISTENT AND NOVEL METRICS, AND IF YOU HAVE ANY QUESTIONS ABOUT THIS ASK SHARON TERRY BECAUSE SHE WAS THE CO-CHAIR OF THE COMMITTEE THAT PRODUCED THIS REPORT. SHE AND ALLEN LESHNER. IT IS A FANTASTIC REPORT, WHICH REALLY GIVES US A ROAD MAP OF WHERE THIS PROGRAM OUGHT TO GO THAT WE'RE STILL FOLLOWING TO THIS DAY, AND IT REALLY IS, TO US, IT'S VERY MUCH A LIVING DOCUMENT. WHAT WE DID AFTER THIS WAS TO -- IT'S SUCH A DENSE REPORT WITH SO MANY GREAT RECOMMENDATIONS IN IT FOR HOW TO TAKE THE STRENGTHS OF THE PROGRAM WHICH HAD BEEN IN PLACE FOR A DECADE, HOW DO WE TAKE IT TO THE NEXT LEVEL IS REALLY WHAT THE COMMITTEE TALKED ABOUT. IT'S SUCH AN INCREDIBLE OBVIOUSLY NATIONAL RESOURCE, HOW DO WE TAKE IT TO THE NEXT LEVEL? AND SO WE PUT IN PLACE AN ADVISORY COUNCIL WORKING GROUP, ON THIS REPORT. SO PLEASE WORKING GROUP OF COUNCIL, PLEASE TELL US HOW DO WE ACTUALLY IMPLEMENT THIS? IOM REPORTS AS YOU PROBABLY KNOW ARE PURPOSELY FAIRLY HIGH LEVEL, AND TWO OF THE PEOPLE WHO WERE ON THAT GROUP ARE RON BARTEK AND LYNN MARKS WHO HAPPEN TO BE, I DIDN'T REALIZE UNTIL I LOOKED AT THE SLIDE, THE TWO PEOPLE NOW ON THE COUNCIL CAN BOARD ARE TWO CHAIRS OF THE CAN REVIEW BOARD, WHICH REDIDN'T DO A PURPOSE. IT JUST SHOWS VIA THIS EFFORT THEY SHOWED US HOW SMART THEY ARE AND SMART PEOPLE ALWAYS GET ASKED TO DO ADDITIONAL THINGS SO HERE WE ARE. AND THIS INVOLVED MANY PEOPLE FROM ACROSS THE CTSA PROGRAM BUT ALSO INVOLVED WHAT WE MIGHT CALL CUSTOMERS, PEOPLE WHO WERE SUPPOSED TO BENEFIT FROM THE WORK THAT THE CTSA PROGRAM DOES, INCLUDING BIOTECH COMMUNITY ENGAGEMENT FOLKS, THIS IS A TRAINING PERSON, AND ALL THESE FOLKS, INSTITUTE DIRECTOR, ET CETERA. REALLY, AGAIN, A FANTASTIC REPORT THAT IF YOU'RE NEW TO THE COUNCIL WHICH MOST OF YOU ARE, OR IF YOU'RE RON OR LYNN AND YOU FORGOT WHAT YOU SAID, YOU CAN GO BACK AND LOOK AT THIS. AGAIN, IT WAS SUCH AN INCISIVE COMPELLING REPORT, LIKE THE IOM REPORT. WE REALLY HAVE TAKEN THIS VERY SERIOUSLY AND ARE STILL RUNNING THE PROGRAM TO A GREAT DEGREE AS A RESULT OF THIS, AS WELL AS THE IMPACT, INPUT OF THE COUNCIL AND P.I.s AND OTHERS ONGOING. SO I WANTED TO GIVE YOU THAT BACKGROUND SO YOU KNOW WHERE THIS CAME FROM, IF YOU'RE NEW. SO THE COMMON METRICS INITIATIVE, WHAT WAS THE PURPOSE OF THIS? WELL, THE PURPOSE IS VERY SIMPLE, IN SOME WAYS. VERY DIFFICULT IN OPERATION. BUT IT WAS TO DEVELOP, IS TO DEVELOP MEASURES TO DEMONSTRATE HOW GREAT THIS PROGRAM IS. WHAT HAS IT ACTUALLY DONE? AND AS PHIL LEE WHO IS OUR RESULTS-BASED ACCOUNTABILITY PERSON WHO HAS BEEN INVOLVED LIKES TO SAY, MANY PEOPLE HAVE COMPLICATED PROGRAMS, AND IF YOU ASK THEM HOW THEY ARE DOING HE SAYS THEY ALWAYS SAY THE SAME THING. WE'RE DOING PRETTY GOOD. DOING PRETTY GOOD. HOW DO YOU KNOW YOU'RE DOING PRETTY GOOD? WELL, WE JUST KIND OF KNOW. AND AS YOU PROBABLY SEE, THERE'S BEEN A LOT OF DEMAND IN THE LAST FIVE YEARS OR MORE TO ACTUALLY MEASURE OUTCOME AND SOCIAL VALUE OF BIOMEDICAL RESEARCH. AND SO I THINK THIS IS ONE OF THE THINGS WE COULD ASK SHARON, IT'S ONE OF THE THINGS I THINK THE COMMITTEE WAS THINKING ABOUT AND CERTAINLY THE WORKING GROUP WAS TAKEN WITH THIS IDEA, AND I'LL JUST GIVE -- THESE ARE QUOTES FROM THE IOM REPORT FORMALIZE STANDARDIZE EVALUATION PROCESSES FOR INDIVIDUALS HUBS AND CTSA PROGRAM AS A WHOLE, USE CLEAR CONSISTENT INNOVATIVE METRICS, ALIGNED WITH PROGRAM'S MISSIONS AND GOALS, AND MOVE BEYOND ACADEMIC BENCHMARKS OR PUBLICATIONS, A NUMBER OF GRANT AWARDS. THIS IS REALLY HARD. IT SOUNDS REALLY SIMPLE. I REMEMBER ASKING SHARON AND ALLEN LESHNER, ESPECIALLY THIS ONE, MOVE BEYOND ACADEMIC -- WHAT ARE WE SUPPOSED TO USE? THEY SAID, WELL, THAT'S WHAT YOU GOT TO FIGURE OUT. THAT'S WHAT WE'RE STILL DOING. BUT THIS IS AGAIN SOMETHING WHICH GOES WAY BEYOND THE CTSA PROGRAM BUT IF THE CTSA PROGRAM CAN'T FIGURE THIS OUT, WHO IS GOING TO FIGURE THIS OUT? AGAIN, BIG HAIRY PROBLEM WE TOOK ON. NO PUN INTENDED, HARRY. [LAUGHTER] AND IT'S PARTICULARLY ACUTE IN TRANSLATIONAL RESEARCH WHERE, AS THE MOTHER OF A RARE DISEASE PATIENT YOU HEARD ME SAY ONCE, I LOVE PUBLICATIONS, I LOVER SCIENTIFIC ADVANCES BUT WHEN MY DAUGHTER IS SICK I CAN'T GIVE HER A PUBLICATION. WHICH SUMS UP THE TRANSLATIONAL PROBLEM, A HUGE PROBLEM FOR US. OKAY. SO BUT IT'S NOT JUST WITHIN NCATS. THESE ARE PAPERS THAT CAME OUT IN THE LAST COUPLE OF -- JUST THIS YEAR ON THIS ISSUE, MEASURING SCIENTIFIC IMPACT BEYOND ACADEMIA, ASSESSMENT IMPACT EXISTING IMPACT METRICS AND IMPROVED PROPOSED IMPROVEMENTS, FROM A GROUP IN THE U.K. THIS ONE NEW TOOLS FOR MEASURING ACADEMIC PERFORMANCE FROM "SCIENCE" IS A REVIEW THAT CAME OUT A COUPLE MONTHS AGO. AND THEN MOST RECENTLY THIS ONE FROM -- YOU PROBABLY CAN'T SEE THIS. THIS IS A PAPER IN "CLINICAL AND TRANSLATIONAL SCIENCE" FROM BRAD EVENOFF AND HIS COLLEAGUES AT WASH U, TACKLING THIS PROBLEM THAT THEY CALL THE TRANSLATIONAL SCIENCE BENEFITS MODEL. IT'S A FRAMEWORK THAT THEY SUGGEST FOR ASSESSING HEALTH AND SOCIETAL BENEFITS OF CLINICAL TRANSLATIONAL SCIENCE. THE IMPORTANT -- SECOND IMPORTANT THING I WANT YOU TO TAKE FROM THIS NOT ONLY IS IT REALLY IMPORTANT BUT IT IS AN AREA OF SCIENCE IN ITSELF. THE QUESTION OF HOW YOU MEASURE THIS, WE ARE APPROACHING AN EXPERIMENTAL WAY. IT'S LIKE ANY OTHER EXPERIMENT. WE DON'T KNOW HOW TO DO THIS. SO WE'RE GOING TO HAVE A HYPOTHESIS, DESIGN EXPERIMENTS, GATHER DATA. IF DATA ACTUALLY ARE PROMISING, THAT THEY ARE ANSWERING AN IMPORTANT QUESTION WE'LL KEEP DOING IT. IF NOT WE'LL CHANGE. WE DON'T HAVE ANY DELUSION THAT WE HAVE THE ANSWER HERE AND I THINK WE REALLY VIEW THIS AS AN AREA OF SCIENCE AND NEEDS TO BE APPROACHED THAT WAY. LIKE EVERYTHING ELSE NCATS DOES, I'VE SHOWN YOU IN THE PREVIOUS EXAMPLES, IT TAKES A VILLAGE TO DO THIS. IT'S TAKEN A VERY LARGE VILLAGE TO DO THIS. THIS IS A LIST OF THE GROUPS THAT HAVE BEEN INVOLVED, CERTAINLY ALL OF THE CTSA P.I.s AND STEERING COMMITTEE, HUBS, METRICS TEAMS, INITIATIVE EXECUTIVE COMMITTEE, TUFTS IMPLEMENTATION TEAM THAT HARRY RUNS, C4 AND CLIC, PROGRAM EVALUATORS AT EACH ONE OF THE CTSA HUB, THE CLEAR ACT TEAM IS PHIL LEE'S GROUP AND COMMON METRICS TEAM AT NCATS AND PROGRAM STAFF. THIS HAS BEEN A MASSIVE EFFORT OVER THE LAST SEVERAL YEARS. WE STARTED WITH THIS QUESTION OF, OKAY, WHAT DOES SUCCESS LOOK LIKE? THE LAST THING WE WANT TO DO IS HAVE YET ANOTHER WIDGET-COUNTING EXERCISE. WE ALL ARE FAMILIAR WITH THOSE. WE'VE ALL BEEN SUGGESTED TO THEM. EVERYBODY ALWAYS MEETS WIDGET COUNTS. THEY PLAY WITH THE DATA. THEY CHANGE WHAT THEY DO IN ORDER TO MEET THE METRICS THAT THEY HAVE TO MEET. AND MANY OF THESE TURN OUT TO BE COUNTER-PRODUCTIVE. SO THE IDEA HERE IS THAT THE DATA -- THINK ABOUT IT LIKE A FIT BIT. I DON'T KNOW WHY YOU SHARE YOUR FIT BIT DATA WITH ANYBODY ELSE. I DON'T BECAUSE I JUST WANT TO USE IT FOR MY OWN -- IT'S MY OWN SELF IMPROVEMENT. AND IF IT'S -- AND THAT'S REALLY WHAT THIS IS. THE DATA ARE USEFUL AND USED BY THE PROGRAM HUBS AND BY NCATS BECAUSE WE HAVE FIDUCIARY RESPONSIBILITY FOR THE PROGRAM TO MEASURE IMPACT OF THE PROGRAM. STRATEGIC MANAGEMENT OF THE PROGRAM, ARE WE IMPROVING -- ADVANCING TRANSLATIONAL SCIENCE OR NOT? IT HAS TO BE COLLABORATIVE, MULTIPLE LEVELS, I'VE SHOWN YOU THIS. IT HAS TO ENHANCE THE IMPACT. IT'S NOT JUST A MATTER OF MEASURING BUT THE WHOLE IDEA IS GENERALLY WHEN YOU MEASURE SOMETHING IT GETS BETTER. JUST BY MEASURING IT. IT'S MAGICAL THAT WAY. BEFORE I GOT A FIT BIT I NEVER DID 10,000 STEPS. NOW I OFTEN DO. AND PEOPLE ARE FUNNY THAT WAY. BUT IT'S TRUE. IT'S TO ENHANCE THE IMPACT AND PROVIDE INFORMATION TO TELL THE STORY. WHEN INDIVIDUAL P.I.s OR I GET ASKED, WE'LL HAVE REAL DATA, NOT, OH, WE'RE DOING PRETTY GOOD. AND WE REALLY NEED THAT. AND IT HAS TO HAVE TRANSLATIONAL IMPACT SO WE CAN MEASURE IMPACT OF THE PROGRAM BEYOND INDIVIDUAL LOB. THE WHOLE PURPOSE DEVELOP, DEMONSTRATE, DISSEMINATE, LIKE NCI'S JOB TO CHANGE CANCER. VERY IMPORTANT THING IN THIS SPACE, IT'S NOT JUST ABOUT THE DATA. WE FREQUENTLY CALL IT THE STORY BEHIND THE DATA. THE STORY MUCH LIKE A MECHANISM OF EXPERIMENT OFTEN TELLS YOU MORE THAN THE DATA ITSELF. WE USE THIS MANAGEMENT FRAMEWORK CALLED RESULTS-BASED ACCOUNTABILITY, IF YOU DON'T KNOW IT'S QUITE USEFUL. THESE ARE METRICS DATA. IF THEY ARE NOT IN THE RIGHT DIRECTION WE'LL CHANGE THE STRATEGY. THIS IS EXPLICITLY SCIENTIFIC METHOD. WHAT HAVE WE DONE SO FAR IN THE BLUE? THESE ARE IMPLEMENTED ACROSS CTSA HUBS. YOU'LL SEE ON THE LEFT IS THE FUNCTION, GENERAL AREA, YOU PROBABLY WANT TO LOOK AT THE METRIC IN THE MIDDLE AND THEN THE IMPACT ON THE RIGHT IS WHY ARE WE DOING THIS, WHAT ARE WE TRYING TO ACHIEVE? SO THERE'S THREE THAT ARE IMPLEMENTED, IRB DURATION, RETAINING SCHOLARS, PARTICULARLY UNDERREPRESENTED AND FEMALE SCHOLARS, AND THE IMPACT OF PILOT PROJECTS. AND THERE ARE TWO UNDER DEVELOPMENT, ONE I'M PARTICULARLY EXCITED ABOUT IS ACCRUAL RATIO. I WANTED TO TELL YOU ABOUT THAT TODAY, ACCRUAL OF CLINICAL TRIALS BUT I WAS CONVINCED I WOULD BE LETTING TOO MANY CATS OUT OF TOO MANY BAGS SO I'LL TELL YOU ABOUT THAT NEXT TIME. I HOPE. DO YOU HEAR THAT, STOVE? STAFF? IT'S A VERY EXCITING THING DRIVING A NUMBER OF IMPROVEMENTS ALREADY. AND THEN INFORMATICS AROUND CLINICAL RESEARCH DATA AND STANDARD FORMAT SO WE HAVE A COMMON LINGUA FRANCA. AND ALL I'M GOING TO DO TODAY IS GIVE YOU ONE BECAUSE WE'RE RUNNING OUT OF TIME HERE. I WANT TO GIVE YOU ONE EXAMPLE OF WHAT THE IRB DURATION EFFORT HAS. SO IN THIS CASE, WHAT CAME OUT OF THE COMMON METRICS IS AN APPRECIATION BY A PARTICULAR HUB THAT THEY WERE BEHIND THE CURVE WHEN IT COMES TO IRB DURATION, AND THEY SHARED THESE DATA AND THE BENCH MARK DATA WITH THE IRB OF THIS INSTITUTION AND CENTER STAFF, WHEN THEY HAD THE DATA WHICH THEY DIDN'T KNOW ABOUT THIS BEFORE, THE INSTITUTION HIRED MORE COMPLIANCE STAFF, HIRED CLINICAL RESEARCH FACILITATORS TO ASSIST CLINICAL RESEARCHERS WITH THE IRB APPLICATIONS, IMPLEMENTED A CLINICAL RESEARCH NAVIGATION SYSTEM, TO PROVIDE PRE-REVIEW OF PROPOSALS BEFORE THE IRB, SO THAT THEY HAD A HIGHER SUCCESS RATE, AND IMPLEMENTED ELECTRONIC COMPLIANCE. THE IMPACT WAS THAT THE NUMBER OF DAYS WENT DOWN BY ABOUT A THIRD, TO IRB REVIEW FROM 78 DAYS TO 50 DAYS. AND YOU NOTICE HERE AS IS TYPICAL LIKE WITH MY FIT BIT I OFTEN DO PRETTY WELL BUT I DON'T OFTEN REACH MY GOAL IMMEDIATELY, I GET STUCK, LIKE I'VE GOT LIKE 8 POUNDS THAT I'VE BEEN TRYING TO LOSE FOR THE LAST YEAR AND I DID PRETTY WELL AND I'M JUST STUCK AND TRYING TO FIGURE OUT HOW TO GET BEYOND THAT. THAT'S WHERE THIS PARTICULAR INSTITUTION IS. BUT THE IMPORTANT THING IS THEY HAVE THE DATA TO FIGURE OUT HOW TO DO THAT. YOU'RE GOING TO HEAR MORE ABOUT IRB EFFORTS THIS AFTERNOON, THAT'S WHY I USED THIS EXAMPLE. THE FUTURE, FUTURE ONES IS METRICS FOR COMMUNITY ENGAGEMENT. WHAT DOES THAT MEAN? WHY WOULD ONE DO COMMUNITY ENGAGEMENT, WHAT IS OUTCOME, DOES IT TRANSLATIONAL SCIENCE, IF SO, HOW? WE HAVE A CLEAR SENSE THIS IS THE RIGHT THING TO DO AND HELPFUL BUT METRICS HAVE BEEN ELUSIVE. SIMILARLY METRICS OF TEAM SCIENCE, HOW DO WE MEASURE THIS? HOW DO WE MEASURE INNOVATION? AND THEN THIS ISSUE OF INTEGRATING SPECIAL POPULATIONS INTO CLINICAL RESEARCH. STAY TUNED ON THOSE. THE LAST THING I WANT TO TELL YOU ABOUT AND THEN I REALLY AM -- I GET REALLY EXCITED TALKING ABOUT SCIENCE BUT I HAVE TO TELL YOU ABOUT THE BUDGET THINGS IS THIS IS ANOTHER THING I'M REALLY EXCITED ABOUT. AND SO IT WENT LIVE YESTERDAY AT FOUR IN THE AFTERNOON. SO I REALLY WANT TO JUST GIVE YOU A LITTLE TICKLER ON THIS. THIS IS A RESULT OF A VERY LONG EFFORT BY ANN PARISSER, PETRA KAUFFMAN, RON BARTEK, OTHER FOLKS, TO PROVIDE PATIENT GROUPS WITH THE TOOLS THEY NEED TO DO WHAT THEY WANT TO DO. I'M GOING TO SHOW YOU REALLY QUICKLY, WHERE IS IT, HERE? YEAH. AND I HOPE YOU'LL LOOK AT THIS, IT'S RARE DISEASES INFO, OR GOOGLE NCATS TOOL KIT, IT GIVES YOU -- THESE ARE -- THINK ABOUT IF YOU WANT TO DO SOMETHING, GO TO HOME DEPOT, RIGHT? YOU WANT TOOLS THAT DO ALL THE THINGS TO BUILD YOUR TOOL SHED. YOU NEED ONE OF THIS, ONE OF THIS, YOU DON'T KNOW WHAT TO START. THAT'S WHAT THIS IS IS EXCEPT THESE ARE TOOLS CREATED BY A VARIETY OF ORGANIZATIONS MOSTLY OUTSIDE OF NCATS, SO I'LL GIVE AN EXAMPLE. GETTING STARTED HERE, IF OUR CONNECTION WILL WORK, WHICH IT PROBABLY WON'T ... , OKAY, HERE WE ARE. AS AN EXAMPLE IN THE DISCOVERY SPACE, HOW TO PUT TOGETHER SCIENTIFIC COLLABORATIONS, ONE OF MY FAVORITES, ALL OF OUR FAVORITES, STARTING A PATIENT REGISTRY, NATURAL HISTORY DATABASE, ONE EXAMPLE HERE, THIS TELLS YOU WHY YOU WOULD WANT TO DO THIS AND TOOLS, FROM FASTER CURES, FROM NCBI, GLOBAL GENES, EUROPEAN COMMISSION EXPERT GROUP ON RARE DISEASE, NORD, HOW TO CREATE A REGISTRY, DO A NATURAL HISTORY STUDY, ET CETERA, ET CETERA. AND THERE'S THESE ACROSS PREPARING FOR CLINICAL TRIALS, FDA REVIEW, WHAT DOES FDA WANT, WHAT HAPPENS AFTER FDA APPROVAL, REMARKABLE TOOLKIT THAT IS JUST GOING TO I THINK TRANSFORM HOW THIS WORK IS DONE. AND I WANT TO RECOGNIZE AGAIN BECAUSE WE HAVE HER HERE, I WANT TO RECOGNIZE SHARON AND HER GROUP BECAUSE A LOT OF THESE HAVE COME FROM -- HERE IS GENETIC ALLIANCE THAT PUT TOGETHER A NUMBER OF THESE. THE LAST THINK WE WANT TO DO IS RECREATE TOOLS. WE WANT TO BRING GREAT TOOLS INTO THE TOOLBOX AND SAY USE THESE. NOW WE'RE -- ON FRIDAY WE'RE GOING TO HAVE A WHOLE SESSION WHERE THIS IS GOING TO BE OFFICIALLY ROLLED OUT. THEN THE QUESTION, HOW TO USE THIS AND WHAT'S NOT IN THE TOOLBOX. IF YOU WANT TO CREATE A PARTICULAR ELEMENT IN EUROPE TOOL SHED AND DON'T HAVE THE RIGHT TOOL CAN WE GET THIS FROM EUROPE, JAPAN, OR DO WE HAVE TO MAKE IT OURSELVES? OKAY. SO JUST TO FINISH UP HERE, REALLY QUICKLY, THIS IS REALLY IN PROCESS. THE 17 BUDGET WE'RE IN THE LAST THROES OF, WE'VE GOT A $20 MILLION INCREASE, MOST WENT TO THE CTSA PROGRAM, $16 MILLION, THIS IS LANGUAGE THAT GOT PUT IN OUR REPORT LANGUAGE, A NUMBER OF CTSA AWARDS, WHAT THEY MEAN HERE IS HUBS, BECAUSE THERE'S LOTS OF OTHER DIFFERENT CTSA AWARDS, INCLUDING NUMBER OF CLINICAL TRIALS, RESEARCH INSTITUTIONS. AGAIN THEY MEAN HUBS HERE, NO LESS THAN THE 2016 LEVEL. AS A RESULT OF SOME CONFUSION ABOUT THE NUMBER OF HUBS AND HOW THE FUNDING WAS BEING USED IN MID-JULY I THINK, YEAH, MID-JULY WE PUT IN PLACE THIS -- SORRY. THIS TABLE, WHICH IS LINKED FROM THE HOME PAGE OF OUR WEBSITE, RIGHT UNDERNEATH BY DIRECTOR'S MESSAGE, THE DIRECTOR'S CORNER, THE NUMBER OF HUBS WE HAVE WHICH IN 20, THIS LAYS OUT HOW ALL THE MONEY HAS BEEN SPENT, WAS SPENT IN FY16 TO REACH THIS $500 MILLION LEVEL WE'LL DO THIS ONCE FY17 IS OVER, WE'LL DO THIS FOR FY17. THIS HAS BEEN VERY HELPFUL FOR THE COMMUNITY CLEARING UP SOME CONFUSION THAT WAS OUT THERE. AND I WANT TO PARTICULARLY THANK PAMELA MCGINNIS WHO DID JUST INCREDIBLE WORK PUTTING THIS TOGETHER IN A VERY SHORT PERIOD OF TIME. SO THE FY 18 BUDGET OF COURSE WE DON'T KNOW BUT THE PRESIDENT'S BUDGET WAS RELEASED IN MAY. IT HAD A RATHER SUBSTANTIAL REDUCTION OF ALMOST $6 BILLION TO NIH, ELIMINATED FOGARTY CENTER, MOVED AGENCY FOR HEALTHCARE RESEARCH QUALITY TO NIH, AND CHANGES THAT WERE SUGGESTED IN THAT PRESIDENT'S BUDGET, BUT AS YOU KNOW AS THE SAYING AROUND HERE GOES, THE PRESIDENT PROPOSES, AND THE CONGRESS DISPOSES. SO THEY ARE THE ONES WHO MAKE THE BUDGET, THE CONGRESS. AND SO THEY HAVE DONE A NUMBER OF HEARINGS, THE HOUSE AND SENATE, OVER THE SUMMERTIME AND THERE WAS A BILL RELEASED FROM THE HOUSE APPROPRIATIONS COMMITTEE IN JULY THAT ALSO HAD LANGUAGE ABOUT THE CTSA HUBS BUT THIS HAD NO FEWER THAN 64 INSTITUTIONS, QUITE A BIT ABOVE WHAT WE HAVE NOW, APPROPRIATIONS COMMITTEE IS CONSIDERING THEIR BILL TODAY, SO WE DON'T HAVE THE BILL LANGUAGE AVAILABLE YET BUT WE CERTAINLY WILL BY THE NEXT TIME. THIS IS NOT DIRECTLY RELEVANT TO HHS BUT I WANT TO LET YOU KNOW THE HOUSE DID PASS WHAT'S CALLED A MINI BUS OF FOUR MILITARY-RELATED BILLS IN THE CURRENT BACK IN JULY, THE HOUSE AND SENATE SPENDING PLANS INTERESTINGLY DO EXCEED THE SPENDING CAPS THAT WERE AGREED TO IN 2011, AND UNLESS SOMETHING CHANGES THIS IS GOING TO TRIGGER SEQUESTRATION AGAIN. THAT IS A LAW THAT IS IN PLACE. IT DOESN'T GO AWAY. IT'S STILL IN PLACE. SO WE'LL SEE WHAT HAPPENS WITH CONGRESS. A PARALLEL TRACK, SO YOU REMEMBER OUR TRICAMERAL OR THREE BRANCHES OF GOVERNMENT, I JUST TOLD YOU ABOUT LEGISLATIVE, ON THE EXECUTIVE SIDE WHAT'S BEEN GOING ON IS A SERIES OF REORGANIZATION EFFORTS, THERE WAS AN EXECUTIVE ORDER, THAT IS FROM THE PRESIDENT, BACK IN MARCH THAT DIRECTS THE OFFICE OF MANAGEMENT AND BUDGET TO CONDUCT A REVIEW AND PROVIDE A PLAN TO REORGANIZE EXECUTIVE BRANCH DEPARTMENTS, EVERY EXECUTIVE BRANCH DEPARTMENT, WITHIN 180 DAYS. IF YOU DO THE MATH, THAT'S SEPTEMBER 13, SO THAT'S COMING UP SOON, TO IMPROVE EFFICIENCY, EFFECTIVENESS AND ACCOUNTABILITY OF FEDERAL AGENCIES. I DON'T THINK ANY OF US WOULD ARGUE THIS IS A REALLY IMPORTANT GOAL, BUT OF COURSE THE QUESTION OF ALL OF THESE IS HOW IS THIS GOING TO BE DONE. SO HHS HAS ITS OWN VERSION OF THIS CALLED REIMAGINE HHS THAT SECRETARY PRICE HAS BEEN WORKING ON, A HIGH PRIORITY FOR HIM, THAT HHS PLAN WAS SUBMITTED TO OMB RECENTLY. YOU CAN SEE THE SIX PRINCIPLES HERE THAT HE HAS ESTABLISHED. DURING THIS TIME, NIH HAS ESSENTIALLY NOT BEEN ABLE TO HIRE AND CERTAINLY NCATS HAS NOT BEEN ABLE TO HIRE AT ALL SINCE JANUARY. AND I WILL NOT SUGARCOAT THIS. THIS IS CAUSING MAJOR STRAINS IN THE ORGANIZATION. I WOULD BE DELINQUENT IN MY DUTIES IF I DID NOT TELL YOU THAT. AND WE HOPE THAT THERE IS RELIEF FROM THIS VERY SOON. WE'RE GLAD TO SEE THE SGE PROBLEM GOT RESOLVED, BUT THERE ARE OTHER MAJOR PROBLEMS, THE BULK OF THE PROBLEMS STILL REMAIN. I WANT TO FINISH WITH A HAPPY NOTE, HOWEVER. AND THIS IS A REMARKABLE DAY THAT WE HAD BACK IN JUNE, NCATS DAY. THIS WAS THE SUBTITLE, PARTNERING WITH PATIENTS FOR SMARTER SCIENCE. OBJECTIVES TO EDUCATE PATIENTS TO INTERACT WITH US TO EDUCATE US ON WHAT PATIENTS WANT AND NEED, AND PROVIDE TANGIBLE EVIDENCE OR EVIDENCE FOR COMMUNICATION. LOTS OF -- SEVERAL HUNDRED PARTICIPANTS, A LOT OF GREAT DISCUSSION, BREAKOUT SESSIONS, RECOMMENDATIONS, FOR ENGAGING PATIENTS IN RESEARCH INCLUDING ON-RAMPS, A TERM MARGARET ANDERSON USED TO USE SHE WAS ON COUNCIL. WE'RE MOVING FORWARD IN AN AGGRESSIVE WAY. WE DO NOT HAVE TIME FOR DISCUSSION BECAUSE YOU PROBABLY ALL WANT TO GO USE THE BATHROOM. WILL LEAVE IT TO ANNA TO TELL US WHETHER WE CAN HAVE A FEW QUESTIONS OR YOU WANT TO PUT THAT OFF UNTIL LATER? WHAT SHOULD WE DO? >> I THINK WE NEED TO SPEND FIVE MINUTES WITH QUESTIONS AND THEN MOVE TO OUR BREAK. >> OKAY. >> GREAT, CHRIS. I WAS STARTING TO THINK THE T IN NCATS STANDS FOR TOUGH SCIENCE, YOU'RE TAKING ALL THE TOUGH THINGS, THE TOUGHEST. REMARKABLE. GENE THERAPY AND iPSC AND COMMON METRICS AND THE LIKE. iPSC STORY, THE LIKES OF JAPAN, AMD AND FOR PARKINSON'S AND PRIMATES HAD AN EFFECT. ARE YOU ENVISIONING THIS TO BE FACILITATIVE ROLE IN THERAPY, ALSO CAN YOU COMMENT ABOUT THE COMBINATION SPEAKING OF TOUGH OF iPSCs PLUS GENOME EDITING? >> YEAH, TWO GREAT QUESTIONS, THANKS. YES, THE GOAL IS TO HAVE THESE DEMONSTRATION PROJECTS RESULT IN THE CLINIC. THE FIRST ONE WE'RE INVOLVED IN IS A MACULAR DEGENERATION PROJECT WITH AN INVESTIGATOR CAT BARTY AT THE NAI, WITH A LONG AND DIFFICULT PROTOCOL THAT'S COMMERCIALLY NOT VIABLE. BUT YES, THAT IS -- SO THE GOAL IS -- AS IS TYPICAL FOR NCATS PROJECTS TO PRODUCE AN INDIVIDUAL ADVANCE FOR AN INDIVIDUAL DISEASE, IN THIS CASE GETTING TO THE CLINIC, BUT ALSO TO GENERATE GENERALIZABLE PROTOCOLS AND DIFFERENTIATION OF METHODS AND THINGS LIKE THAT. SO IT'S BOTH. THE GENE EDITING QUESTION IS REALLY INTERESTING. ERIC'S ABSOLUTELY RIGHT THAT THE COMBINATION OF THESE TECHNOLOGIES HAS REALLY QUITE INCREDIBLE POTENTIAL, SEPARATELY THEY DO BUT TOGETHER IT'S QUITE REMARKABLE. SO WE HAVE AT NCATS AND PERHAPS I'LL TALK ABOUT THIS NEXT TIME, WE HAVE A GENE EDITING GROUP STARTED OUT AS AN siRNA GROUP, NOW MAINLY A CRISPR GROUP, FOCUSED ON THOSE TECHNOLOGIES WITH THE KIND OF OPERATIONAL MODEL THAT WE ALWAYS USE. AND SO THOSE TWO GROUPS WITH JUST BEGINNING TO WORK TOGETHER AND WE'RE GOING TO BE GUIDED BY WHAT THE APPLICATIONS ARE THAT PEOPLE COME TO US WITH. AND SOME OF THEM WILL PROBABLY BE STRAIGHT DIFFERENTIATION, LIKE THE MACULAR DEGENERATION ONE IS, BUT SOME WILL PROBABLY BE GENE EDITING AS WELL, WHICH WOULD BE TREMENDOUSLY EXCITING. AND IN THE THEME OF ADVANCING TOUGH SCIENCE, WE LOVE PROJECTS LIKE THAT. AND SO IF WE CAN -- THE HARDER, THE BETTER, FROM OUR POINT OF VIEW, YEAH. IF YOU HAVE ONE, PLEASE, SOMEBODY AT SCRIPPS, PLEASE LET US KNOW. YEAH? >> HI, CHRIS. THIS WAS QUITE INTERESTING, AS A NEWBY, AS YOU PUT IT. BUT FROM A GENE THERAPY POINT OF VIEW I'M WONDERING TO TRY AND FIGURE OUT THE PROCESS. YOU KNOW VOYAGER THERAPEUTICS IS DEVELOPING AN AADC THERAPY FOR PARKINSON'S DISEASE, SO WHEN DO YOU DECIDE NOT TO SPIN EXISTING WHEELS, WHEN DO YOU REACH OUT TO COMPANIES THAT SAYS, OH, COMPANIES TO YOU -- >> YEAH, THEY COME TO US. >> THINGS LIKE THAT. >> YEAH, SO WE WOULD NEVER TAKE ON PARKINSON'S DISEASE. IT'S TOO COMMON. IT'S-- I I CAN'T BELIEVE I'M SAYING THIS. IT'S TOO EASY. YOU KNOW WHAT I MEAN BY EASY. THERE ARE OTHERS WHO WILL DO THIS. AND THERE'S BEEN A LOT OF GREAT WORK. STILL IS GOING ON IN THAT SPACE. NOT THAT IT'S SOLVED BY ANY MEANS BUT WE WOULDN'T DO THAT WE LOOK FOR PROJECTS WHERE THERE'S NO ONE WORKING IN THAT SPACE, SO THESE ARE ALMOST ALWAYS UNTREATABLE DISEASES, OFTEN RARE DISEASES, WHERE THERE IS AN OPPORTUNITY FOR US TO DEVELOP SOME GENERALIZABLE APPROACH. SO IF A NEUROLOGICAL INSTITUTE, THEY WOULD DO A GENE THERAPY PROJECT FOR PARKINSON'S DISEASE BECAUSE THEIR PURPOSE IS TO DEVELOP UNDERSTANDING AND TREATMENTS FOR PARKINSON'S DISEASE. IF THEY HAVE A GENERALIZABLE OUTCOME, GREAT. WE LOOK AT PROJECTS UPSIDE DOWN. WE SAY WE'RE INTERESTED IN GENERALIZABLE SOLUTIONS APPLICABLE ACROSS ANY DISEASE, AND WE FRANKLY DON'T CARE WHAT THE INDICATION IS. IT COULD BE ANYTHING. >> LET ME REPHRASE BECAUSE THE CONSTRUCT IS APPLICABLE TO RARE AND COMMON DISEASES, SO WHEN -- YOU KNOW, WHY ADULIS AND NOT EXISTING -- >> OH. >> RIGHT. >> THAT'S SIMPLE. THE WAY THIS WORKS IS -- IT'S A BIT OF A STRANGE BEAST. IT'S AN INTRAMURAL PROGRAM BUT EVERY PROJECT IS DONE VIA PEER REVIEW. SO WE PUT OUT SOLICITATIONS, ACADEMICS AND COMPANIES COME TO US, PEER REVIEW, BIOTECH AND PHARMA LOOK AT THESE AND WE PICK THE BEST ONES BASED ON THAT. SO THEY CAME TO US, THIS IS THE SHORT ANSWER, YEAH. YEAH? >> I LOVE THAT RARE DISEASE WEBSITE, AND I HOPE YOU'LL LEARN FROM IT. IT'S SPECTACULAR WHAT YOU'RE TRYING TO DO, ENGAGE THE PATIENTS AND REALLY EDUCATE THEM. I DON'T KNOW WHAT KIND OF METRICS OR MEASURES OR JUST INFORMATION YOU WANT TO COLLECT BUT I WOULD COLLECT AS MUCH AS YOU CAN BECAUSE IT'S AN INTERESTING MODEL OF ENGAGING THE PROBLEM IN THE ADDRESSING OF A DISEASE AND GIVING THEM THE TOOLS TO DO IT BUT THEY WILL QUICKLY REALIZE THEY NEED PARTNERS. >> YES. >> YOU COULD HAVE AN IGNITING PROPERTY. FIGURE OUT WHAT YOU DID THERE, DO IT AND SPREAD IT TO OTHER PROBLEMS BECAUSE IT'S JUST A REALLY NEAT IDEA. >> BEAUTIFUL. GREAT IDEA. THANK YOU. >> SO I HAVE AN INTEREST IN TRYING TO FIGURE OUT HOW WE TAKE THE RARE DISEASES AND TREATMENTS, AND THEN THEY BECOME GENERAL TREATMENTS. AND HOW WE FACILITATE THAT. SO I HAD THE WONDERFUL OPPORTUNITY TO HAPPENING OUT WITH ADDY AND CASSIE WHEN THEY WERE ABOUT 4, AND SAW ALL THE WORK THAT CHRIS AND HUSBAND PUT THROUGH TO PUSH THIS ALONG. I HAVEN'T SEEN ANYTHING UPDATED ON THE WEBSITE IN A WHILE SO I'M JUST HOPING THAT MEANS EVERYTHING IS ADVANCING. HOW DOES NCATS HELP WITH ONCE WE SEE SOME SIGNIFICANT IMPACT TO MAKING THIS COMMON THERAPY? >> IT'S A GREAT QUESTION. WE'RE REALLY -- WE THINK ABOUT OUR WORK LIKE THE TREE FALLING IN THE FOREST. IF ALL WE DO IS DEVELOP AND DEMONSTRATE AN INDIVIDUAL CASE, BUT NOBODY KNOWS ABOUT IT, WE FAILED. AND SO WE SPENT A LOT OF TIME THINKING ABOUT THE WHOLE AREA OF WHATEVER TERM ONE WANTS TO USE. IN THE CASE OF -- SPECIFIC CASE OF THE NPC PROJECT, WE'VE ACTUALLY WRITTEN TWO HOW-TO PAPERS. ONE OF THEM WRITTEN BY THE WHOLE TEAM ABOUT WHY DID THIS WORK. AND IF YOU WANT TO DO THIS AT HOME, HOW DO YOU DO IT? WHAT WERE THE SUCCESS FACTORS? IT IS IN THE PUBLISHED LITERATURE. AND ONE OF THE THINGS WE'VE WONDERED ABOUT, YOU KNOW, IS EVERYTHING IN THE RIGHT PLACE FOR THIS? OR SHOULD WE PUT THAT LIKE ON THE TOOLKIT OR SOMETHING? YOU KNOW, BECAUSE PARENTS PROBABLY DON'T HAVE A SUBSCRIPTION TO SOME SCHOLARLY JOURNAL, THAT'S PART OF THE PROBLEM. WE ALSO -- WHENEVER POSSIBLE, WE WORK VERY HARD TO EDUCATE OUR OTHER IC INSTITUTE DIRECTOR FOLKS HERE, AND SO ONE EXAMPLE I WAS TALKING WITH ELIZABETH ABOUT LAST WEEK, SOMETHING FRANCIS IS INTERESTED, IN ALL THE THINGS WE'RE TALKING ABOUT RELEVANT TO SICKLE CELL. SO HERE'S SOMETHING FRANCIS HAD AN INTEREST IN A LONG TIME, I'VE HAD AN INTEREST IN A LONG TIME, ELIZABETH. THERE'S A LOT OF EXPERTISE HERE. IT'S NOT A RARE DISEASE. SO -- AND WE WOULD NEED GARY'S HELP IN THIS BUT IT'S THAT KIND OF THING WE'RE HOPING THAT IF WE CAN DEMONSTRATE THESE KINDS OF SUCCESSES THEN THAT WILL BE BEYOND A POINT FLY PAPER, IT'S ONE OF THE -- IT'S A FASCINATING BUSINESS, YOU KNOW, THAT WE'RE RUNNING INTO CULTURALLY I THINK, IT GOES LIKE THIS. THAT MOST OF THE TRANSLATIONAL WORLD IS VERY PARTICULAR ABOUT SECRECY. THEY ACTUALLY DON'T SHARE SECRETS OF SUCCESS. THIS IS THE WAY THIS IS DONE. SO THERE ACTUALLY IS NOT A VERY WELL DEVELOPED ECOSYSTEM FOR PEOPLE TO TAKE IN THESE KINDS OF IDEAS. FOR THE MOST PART, THEY HAVE NEVER BEEN THERE BEFORE. PEOPLE ARE DISORIENTED WHEN WE SAY, NO, NO, THIS IS -- THIS IS HOW YOU DO IT. I MEAN WHEN I WAS BACK AT MERCK, I PROBABLY SHOULDN'T SAY THIS, THIS IS MANY YEARS AGO, I'M SURE IT DOESN'T HAPPEN NOW. FROM A COMPETITIVE STANDPOINT THE IDEA WAS YOU WANT YOUR COMPETITORS TO GO INTO A DITCH, SO YOU WOULDN'T GIVE THEM GOOD INFORMATION. YOU LEARNED NOT TO TRUST THE INFORMATION FROM OTHER PLACES. THAT'S JUST THE WAY THE GAME WAS PLAYED. AND SO WE'RE SUCH A DIFFERENT ANIMAL IN THIS ECOSYSTEM THAT OUR PURPOSE IS TO SHARE DATA AND ENABLE OTHER PEOPLE THAT THE FIELD IS TAKING A WHILE TO REALLY TRUST THAT. IT'S FASCINATING. >> I THINK PART OF THE -- OF COURSE THE CONCERN IS THE DISCLAIMER YOU WANT ON THERE, DON'T TRY THIS AT HOME, OKAY? HOW YOU BALANCE THAT DISCLAIMER, DON'T TRY THIS AT HOME, WITH -- THAT'S EXACTLY WHAT PEOPLE ARE DOING, TRYING IT AT HOME >> THE LESSON, TRY TO KEEP -- YOU KNOW, OVER AND OVER AGAIN, THE ONLY REASON THIS WORKED IS THAT WE DID IT AS A TEAM. IF NCATS TRIED TO DO ANY OF THESE THINGS ALONE WE WOULD HAVE FAILED MISERABLY. THERE'S JUST NO QUESTION ABOUT IT. AND THAT'S ONE OF THE MAJOR LESSONS. >> WE'VE GOT TIME FOR ONE MORE QUESTION. >> SHARON? >> JUST A COMMENT, CHRIS, THAT AS PART OF THE TRANSITION FROM PCORnet TO THE PEOPLE-CENTERED RESEARCH FOUNDATION WHICH I'M LEADING THE TRANSITION TEAM FOR WE'VE DEVELOPED METRICS FOR ENGAGEMENT. AND SO WE CAN GIVE WHAT YOU WAS AN ASSESSMENT TOOL IN PCORnet BECAUSE NO ONE WANTED REQUIREMENTS WHICH HAVE BECOME REQUIREMENTS IN PCRS. >> FANTASTIC. >> SHE PARTIALLY ANSWERED MY QUESTION. I THINK THIS, AS YOU DEMONSTRATED, THERE'S BEEN A LOT OF GREAT WORK AND I LOVE THE PHRASE LIKE ERIC SAID, THIS IS TOUGH SCIENCE. YOU SHOULD PROBABLY PUT IT ON YOUR WEBSITE. [LAUGHTER] I THINK THE NEXT BIG CHALLENGE OR BURNING PLATFORM IS ALL THE COMMUNITY DISENGAGEMENT AND HEALTH EQUITY ISSUES AND IMPLEMENTATION OF EVEN COMMON TREATMENTS THAT WE KNOW WORK WELL, AND THERE'S A WHOLE NEED FOR INNOVATION THERE. >> YES. >> TRANSLATIONAL TOOLS THERE. >> YES. >> AND I KNOW THAT IT'S PROBABLY AN ORDER OF MAGNITUDE TOUGHER THAN MANY THINGS WE'RE DOING. I HOPE THAT BECOMES A BIG FOCUS FOR THE NEXT YEAR OTHER TWO. >> YEP. THANK YOU FOR THAT SUGGESTION. I ACTUALLY HAVE BEEN TALKING TO THE CTSA DCI STAFF ABOUT JUST THE KIND OF THINKING THAT TEAM AND P.I.s PUT TOGETHER INTO IRB, TRIAL INNOVATION NETWORK, REALLY INNOVATIVE APPROACH AND THAT'S GREAT FOR THAT SPACE. BUT THAT'S A PARTICULAR PART OF TRANSLATION, TO SAY, OKAY, WE GOT A LOT OF STUFF TO DO THERE BUT LET'S NOW DO THE SAME THING FOR THIS SPACE, EXACTLY THE SPACE THAT YOU'RE TALKING ABOUT. AND WE WOULD BE VERY ENTHUSIASTIC ABOUT THAT AND ANY INSIGHTS THAT YOU ALL HAVE TO DO THAT BECAUSE WE ALSO FEEL LIKE THE IRB AND TRIAL INNOVATION NETWORK AND OTHER THINGS, RECRUITMENT, THERE ARE SOME REALLY TANTALIZING EXAMPLES OF WHAT WORKS, BUT IT'S SO FAR FROM UNDERSTANDING GENERAL PRINCIPLES AND IMPLEMENTATION AND SYSTEMIZATION, THAT'S REALLY WHAT WE NEED TO DO. OKAY. >> NEXT WE'LL HAVE A SHORT BREAK. WE DO NEED THE SAME AMOUNT OF TIME FOR THE BREAK PRETTY MUCH BUT WE ASK EVERYONE TO BE BACK BY 10 -- BE BACK BY 20 AFTER. YOU'VE GOT TEN MINUTES. WE'RE BORROWING TIME FROM LUNCH NOW. NOW WE HAVE FOUR CONCEPT CLEARANCES. TO REMIND YOU WHAT A CONCEPT CLEARANCE IS, WE ARE REQUIRED, IN ADDITION TO THE FACT WE LIKE TO, WE ARE REQUIRED TO BRING IDEAS TO YOU THAT WE ARE THINKING ABOUT PUTTING MONEY TOWARD OR HAVE PUT MONEY TOWARD IN THE PAST LIKE RDCRN, TO HAVE YOU GIVE US YOUR ADVICE ON WHETHER YOU THINK THIS IS A GOOD USE OF TAXPAYERS' DOLLARS. WE TAKE OUR FIDUCIARY RESPONSIBILITY SERIOUSLY, I KNOW YOU DO. THE CONCEPT CLEARANCES, WHEN YOU HEAR THEM, YOU SHOULD SAY IS THIS AN IMPORTANT PROBLEM? DOES IT REALLY RISE TO THE TOP OF THE PROBLEMS THAT NCATS OUGHT TO BE WORKING ON? AND THAT MEANS TWO THINGS. ONE, IT HAS TO BE AN IMPORTANT PROBLEM AND TWO, WITHIN NCATS' WHEELHOUSE OF WHAT OUR MISSION IS. SO WHAT WE'RE NOT DOING, TALKING ABOUT MONEY, MECHANISM, DETAILS, IT'S REALLY WHAT IT SAYS. IT IS A CONCEPT OF WHETHER YOU THINK THIS IS A REASONABLE USE OF THE NCATS BUDGET. SO WE HAVE FOUR. THE FIRST IS RARE DISEASES, ACTUALLY THREE THAT YOU'LL KNOW ABOUT, RARE DISEASES AND TWO ON TISSUE CHIP, AND A NEW ONE, THE ONE ON CHEMISTRY AND BIOLOGY THAT I MENTIONED BEFORE. SO THE FIRST ONE IS DONE BY ANN, AND WE'LL BE TAKING A VOTE AFTER EACH ONE. FOR TIME PURPOSES WE'RE GOING TO RUN THROUGH THE PRESENTATIONS AND TAKE A VOTE AT THE END. TAKE THE AWAY. >> GOOD MORNING. I'M ANN PARISSER WITH THE OFFICE OF RARE DISEASE AT NCATS. I'D LIKE TO SPEND A FEW MINUTES TALKING ABOUT THE CLINICAL DISEASE NETWORK, THE FOURTH COMPETITION. THIRD RECOMPETITION OR FOURTH COMPETITION TYPE HERE. SO WHAT IS THE RDCRN? WELL, THIS IS THE FOURTH COMPETITION IMPLIES, AN ESTABLISHED PROGRAM AT NCATS, AND IT WAS STARTED WITH THE PURPOSE OF TRYING TO FACILITATE AND SUPPORT RARE DISEASE RESEARCH IN A COLLABORATIVE MANNER BY ESTABLISHING RESEARCH CONSORTIA THAT WOULD ALLOW PHYSICIAN-SCIENTISTS, OTHER TEAM MEMBERS AND PATIENT ADVOCACY GROUPS TO STUDY RARE DISEASES IN A COLLABORATIVE MANNER. SO IT INCLUDES CENTRALIZED DATA COORDINATION AND DATA SHARING, WHICH IS REALLY THE GLUE THAT HOLDS THE NETWORK TOGETHER. IT TRIES TO ESTABLISH PUBLIC RESOURCES IN EDUCATION FOR RARE DISEASES GENERALLY, NOT LIMITING TO JUST THE DISEASES IN CONSORTIA. PROVIDE AVENUE FOR TRAINING AND VERY IMPORTANTLY PATIENT INVOLVEMENT. SO VERY BRIEFLY, THE HISTORY GOES BACK TO 2002 WITH THE ENACTMENT OF RARE DISEASES ACT, WHICH DIRECTED NIH TO SUPPORT REGIONAL CENTERS OF EXCELLENCE. THIS EVOLVED IN 2003 TO THE ESTABLISHMENT OF THE RDCRN, WHICH FOR THE FIRST ITERATION INCLUDED TEN CLINICAL RESEARCH CONSORTIA PLUS DATA MANAGEMNT AND COORDINATING CENTER. IT STARTED IN 2006, IN 2008 RECOMPETED, EXPANDED TO 17 CONSORTIA, RECOMPETED IN 2013, EXPANDED TO 21 CONSORTIA, THE CYCLE WE'RE IN. THE CURRENT CYCLE. RDCRN 3, INCLUDES 21 PLUS THE DMCC, APPLICANTS ARE REQUIRED TO PROPOSE UNIFYING THEME OF THREE OR MORE DISEASES, THREE OR MORE THERAPEUTIC AREAS THAT THE RESEARCH IS GROUPED AROUND. SO THIS COULD BE FOR EXAMPLE AROUND AN ORGAN SYSTEM, RARE LUNG DISEASE OR BRITTLE BONE, COULD BE AROUND AN ORGANELLE, METABOLIC PATHWAY, SO WE HAVE CONSORTIA AROUND ALL THESE THINGS, QUITE NARROW OR VERY BROAD, AND THEY ALL WORK. SO THROUGH THIS MODEL WE'VE BEEN ABLE TO COVER CURRENTLY 200 DIFFERENT RARE DISEASES, AND ANOTHER REQUIREMENT IS THESE HAVE TO BE MULTI-SITE. SO ALL OF OUR CONSORTIA ARE MULTI-SITE, RANGE FROM 7 TO 44 CENTERS THAT PARTICIPATE WITHIN A CONSORTIA, MEDIAN IS ABOUT 20, AND WE HAVE RIGHT NOW WE INCLUDE NEW CONSORTIA THAT HAVE BEEN AROUND FOR 3 YEARS, AND ESTABLISHED CONSORTIA THAT HAVE BEEN AROUND REALLY THROUGHOUT THE PROGRAM. TODAY TO DATE WE HAVE 100 ACTIVE PROTOCOLS, INCLUDED MORE THAN 32,000 PATIENTS WHICH FOR RARE DISEASES IS JUST HUGE. AND TRAINED MORE THAN 350 TRAINEES, WHICH FOR RARE DISEASES IS HUGE. CURRENTLY INCLUDE 140 PATIENT ADVOCACY GROUPS WHICH IS WONDERFUL. THE CURRENT CRITERIA OR WHAT WE'RE CURRENTLY FUNDING IS THERE'S A CAP OF 1.$25 MILLION TOTAL FUNDING FOR CONSORTIA, ICs CONTRIBUTE TO THIS $1.25 MILLION, AND THEY CONTRIBUTE PROJECT AND SCIENTIFIC OFFICERS TO STEER THE PROGRAM AND INTERACT WITH THE CONSORTIUM SITES. AND ORDR ALONE FUNDS THE DMCC, CLOSE TO $6 MILLION PER YEAR. CONSORTIA ARE REQUIRED TO DO TWO OR MORE STUDIES, ONE OF WHICH HAS TO BE OBSERVATIONAL SUCH AS NATURAL HISTORY STUDY, ALSO HAVE THINGS LIKE BIOBANKING AND DIFFERENT FORMS OF REGISTRIES, AND THE DATA IS REQUIRED TO BE SHARED THROUGH THE DMCC WHICH IMPOSES STANDARDS, CLEANS THE DATA, CURATES THE DATA AND THEN THE DATA IS THEN TRANSFERRED TO NIH'S dbGAP WHERE IT CAN BE SHARED TO ANY INVESTIGATOR AROUND THE WORLD ACTUALLY CAN REQUEST ACCESS TO DATA THROUGH THIS MECHANISM. AND AS I MENTIONED HAVE TO HAVE AT LEAST ONE ASSOCIATED PATIENT ADVOCACY GROUP BUT IN REALITY HAVE QUITE A FEW MORE. CURRENT 5-YEAR FUNDING CYCLE ENDS JUNE 30 TO AUGUST 31 OF 2019, SO WE'RE LOOKING AHEAD. SO WE WOULD LIKE TO PUT FORWARD FOR YOUR CONSIDERATION, WE WOULD LIKE TO RECOMPETE THE RDCRN FOR A FOURTH CYCLE, 5-YEAR COOPERATIVE AWARDS AIMING FOR 20 CONSORTIA, NEW AND ESTABLISHED, CRITERIA SIMILAR TO RDCRN 3 AND COMPETE ONE COOPERATIVE AWORD FOR DMCC ALSO A 5-YEAR AWARD. WHAT IS THE POTENTIAL IMPACT? THE MISSION IS TO ACCELERATE RARE DISEASE RESEARCH TO BENEFITS PATIENTS, SUPPORTS CENTERS OF EXCELLENCE, MAINLY PROVIDING INFRASTRUCTURE AND MECHANISM FOR COLLABORATION ACROSS THE RESEARCH CENTERS, AND THIS ALSO ALLOWS FOR INVESTIGATORS TO GET ADDITIONAL GRANTS SUCH AS RO1s TO SUPPORT PILOT PROJECTS OR OTHER TRIALS AND I BELIEVE ALL OF OUR NETWORKS ARE DOING THIS. CRITERIA FOR EVALUATING SUCCESS MAINLY QUANTITATIVE. WE CAN COUNT CONSORTIA, HOW LONG THEY HAVE BEEN IN EXISTENCE, WHAT KIND OF RESEARCH, HOW MANY ACTIVE PROTOCOLS, HOW MANY PATIENTS INCLUDING TRAINEES BUT WE ALSO IN SPEAKING WITH OUR PARTNERING ICs, CONSORTIA THEMSELVES, THE PATIENT GROUPS, WHAT WE ALSO HEAR IS JUST THAT THIS HAS BEEN TREMENDOUSLY SUCCESSFUL PROGRAM, WE OFTEN HEAR OUR DISEASE OR DISEASES WERE NOWHERE BEFORE THE FUNDING AND WE'VE BEEN ABLE TO ESTABLISH A RESEARCH AGENDA AND SUPPORT A NUMBER OF THINGS THROUGH THE WORK OF NCATS AND OUR PARTNERS. SO REALLY THE MAJOR OBSTACLE, THERE'S REALLY THE ONLY ONE WE COULD COME UP WITH, THERE'S 7,000 RARE DISEASES, WE'RE COVERING 200. OF COURSE, WHAT WE LEARN FROM THIS, WE CAN SPREAD TO THE COMMUNITY BUT WE JUST WISH WE COULD DO MORE. SO ANYWAY -- >> THE NEXT ONE, NEXT PRESENTATION IS GOING TO BE BY (INDISCERNIBLE) WHO IS GOING TO TELL US ABOUT A NO CONCEPT, SOMETHING WE'RE CALLING A SPIRE. >> THIS IS AUTOMATED SYNTHESIS PLATFORM FOR INNOVATIVE RESEARCH AND EXECUTION, OR ASPIRE, DEVELOPED BY NCATS STAFF, VETTED THROUGH MULTIPLE LEVELS OF NCATS LEADERSHIP. SO WHAT IS THE SPIRE ABOUT? SO THE GOAL OF THE SPIRE IS TO CONVERGE RECENT ADVANCES IN AUTOMATION ENGINEERING, SYNTHETIC CHEMISTRY, MACHINE LEARNING, BIOCHEMICAL SCREENING IN ORDER TO ALLOW US TO ACCESS MORE OF THE BIOLOGICALLY RELEVANT CHEMICAL SPACE. WHAT DOES THIS MEAN AND WHY IS THIS IMPORTANT? SO THIS SLIDE IS CROWDED BUT I'LL TRY TO EXPLAIN IT AS CLEARLY AS I CAN. I WILL START WITH A CHEMICAL SPACE. CHEMICAL SPACE IS BASICALLY ALL MOLECULES THAT WE COULD SYNTHESIZE, AND WITHIN THIS SPACE THERE'S A SMALLER PROPORTION BUT STILL HUGE OF MOLECULES THAT POTENTIALLY COULD BE PHARMACOLOGICALLY ACTIVE. AND BY PHARMACOLOGICALLY ACTIVE, THESE ARE THE MOLECULES THAT COULD HAVE BENEFICIAL OR ADVERSE EFFECTS ON A BIOLOGICAL SYSTEM. SO WHEN WE ARE LOOKING TO FIND A NEW TREATMENT, WE NEED TO IDENTIFY TARGETS AND THEN FIND DRUGS THAT CAN MODIFY THESE TARGETS AND INFLUENCE DEVELOPMENT OF A DISEASE AND PROGRESSION OF A DISEASE. AND THIS SEARCH FOR TARGET IS CALLED EXPLORATION OF BIOLOGICAL SPACE. COMPARED TO CHEMICAL SPACE, BIOLOGICAL SPACE IS MUCH SMALLER. SO IT LOOKS LIKE IF WE HAVE FEWER TARGETS AND ALL THESE POSSIBILITIES IT SHOULD BE RELATIVELY EASY TO FINDS NEW TREATMENTS. HOWEVER MOST BIOLOGICAL SPACE 90 PERCENT OF IT IS CURRENTLY UNDRUGGED. SO THE MAIN CHALLENGE OF TRANSLATION IS TO THEN LINK NEW CHEMICAL SPACE WITH THIS UNDRUGGED BIOLOGICAL SPACE. AND WE USUALLY USE CHEMICAL REACTIONS TO EXPLORE CHEMICAL SPACE. HOWEVER, AFTER ALMOST A CENTURY OF SYNTHETIC ORGANIC CHEMISTRY WITH CURRENTLY AVAILABLE CHEMICAL REACTIONS WE CAN ACCESS ONLY A SMALL FRACTION OF THIS POTENTIALLY ACTIVE BIOLOGICAL SPACE AND THAT'S ACTUALLY LESS THAN ^. 1%. SO THIS IS REALLY REALLY BAD. AND IN ADDITION TO HAVING THIS VERY NARROW TOOL KIT TO WORK WITH, WE ALSO ARE BAD IN PREDICTING CHEMICAL REACTIONS A PRIORI AND CANNOT PRODUCE NEW CHEMICAL STRUCTURAL CHEAPLY AND QUICKLY. SO WE'RE NOW BACK AT THE GOAL OF THE SPIRE, WHICH IS AGAIN TO COMBINE SYNTHETIC CHEMISTRY, ROBOTIC AUTOMATION, HIGH-THROUGHPUT SCREENING AND MACHINE LEARNING, IN ORDER TO IDENTIFY NEW CHEMICAL SPACE THERAPEUTIC POTENTIAL. THE FIRST OUTCOME WILL TAKE PLACE OCTOBER 19 AND 20 IN BETHESDA. THE OBJECTIVE IS TO IDENTIFY KEY NEEDS IN THIS AREA, AND BASICALLY FIND LOW-HANGING FRUITS THAT, YOU KNOW, SO WE CAN GET THE BIGGEST RETURN FOR ANY POTENTIAL NCATS INVESTMENT. IN ADDITION WE'RE LOOKING TO ENGAGE OTHER STAKEHOLDERS, INCLUDING OTHER GOVERNMENT AGENCIES, SCIENTISTS IN ACADEMIA AND INDUSTRY, PROFESSIONAL SOCIETIES AND SCIENTIFIC JOURNALS. SO COUNCIL MEMBER DR. PALKOWITZ WILL BE ONE OF THE PRESENTERS, YOU CAN FIND A LINK TO THE DRAFT AGENDA IN THE ELECTRONIC VERSION OF THE CONCEPT CLEARANCE RECORDS. THE SECOND OUTCOME OF THIS WILL BE DEVELOPMENT AND IMPLEMENTATION OF HIGHLY COLLABORATIVE CROSS DISCIPLINARY PROBLEM IN BIOLOGICALLY RELEVANT CHEMICAL ENTITIES. AND FINAL OUTCOME INCREASE IN THE DIVERSITY OF PHARMACOLOGICALLY RELEVANT CHEMICAL LIBRARIES. WHAT'S THE POTENTIAL IMPACT OF THE SPIRE? WELL, WE'RE CERTAINLY DISCOVERING NEW TREATMENTS USING CURRENTLY AVAILABLE TOOLS IN CHEMISTRY. WE ALL AGREE THERE'S A LOT OF ROOM FOR IMPROVEMENT. AND THIS IS WHERE SPIRE WILL HELP CATALYZE AND DEVELOP TECHNOLOGY AND BRING TREATMENT TO PEOPLE MORE QUICKLY, EXACTLY THE MISSION OF NCATS. ASPIRE WILL INCREASE REPRODUCIBILITY AND RIGOR IN AGREEMENT WITH THE NIH'S MISSION. AND THE CRITERIA FOR EVALUATING THE SUCCESS OF ASPIRE WILL BE AGAIN AN INCREASED ACCESS TO CURRENTLY UNDISCOVERED BIOLOGICALLY RELEVANT CHEMICAL SPACE, USING NOVEL TOOLS AND TECHNOLOGIES THAT ARE READILY AND VITALLY ADOPTED BY SCIENTISTS. WE WILL NOT BE SUCCESSFUL IF THE LAST THING ALSO DOESN'T HAPPEN. AGAIN, MAJOR OBSTACLES, REDUNDANT TO WHAT I SAID, MORE THAN 99.9% OF BIOLOGICALLY RELEVANT CHEMICAL SPACE IS UNEXPLORED, CHEMISTRY IS VERY MUCH BASED ON EMPIRICALLISM, AND THE CURRENT PROCESS FOR CHEMICAL ARE TIME CONSUMING AND EXPENSIVE. THERE ARE GOVERNMENT-FUNDED PROGRAMS SUCH AS DARPA MAKE-IT PROGRAM, MAINLY FOCUSED ON AUTOMATION OF KNOWN CHEMISTRIES. IN ADDITION, INDUSTRY IS INTERESTED VERY MUCH IN DEVELOPING AUTOMATED MANUFACTURING WITH SPECIFIC ACTIVE PHARMACEUTICAL INGREDIENTS, BUT AGAIN THIS IS USING EXISTING CHEMISTRIES. AND THERE ARE CERTAINLY NOTABL EFFORTS, NOW BEGINNING TO CONVERGE THIS TECHNOLOGIES WITH GOAL TO INCREASE DIVERSITY OF PHARMACOLOGICALLY RELEVANT CHEMICAL LIBRARIES. SO WE BELIEVE THE TIME IS NOW FOR INITIATIVE SUCH AS ASPIRE TO COME IN AND HELP CATALYZE THE FIELD AND AS AN EXAMPLE NCATS TISSUE CHIP PROGRAM IS A PRIME EXAMPLE OF HOW DIFFERENT TECHNOLOGIES CAN BE CONVERGED AND ADVANCE THE FIELD. THIS IS MY FINAL SLIDE. AND THIS IS CAN REVIEW BOARD CAME WITH A SET OF CRITERIA, AND EACH NO CONCEPT NEEDS TO FULFILL THESE CRITERIA. THE CRITERIA INCLUDED CONCEPT NEEDS TO BE COLLABORATIVE, HAVE MEASURABLE OUTCOMES, BROAD AND SIGNIFICANT IMPACT AND DISEASE RELEVANCE. ASPIRE WILL BE COLLABORATIVE. IT WILL FOSTER MULTI-DISCIPLINARY COLLABORATIONS ACROSS GOVERNMENT AGENCIES, INDUSTRY, ACADEMIA, PROFESSIONAL SOCIETIES. IT WILL ALSO OFFER PARTNERSHIP OPPORTUNITIES WITH OTHER GOVERNMENT AGENCIES, NIH INSTITUTES AND CENTERS, AND PHARMA, AND THIS PARTNERSHIP OPPORTUNITIES CAN BE IN THE FORM OF EXCHANGING EXPERTISE OR CO-FUNDING OPPORTUNITIES OR BOTH. I HAVE PREVIOUSLY MENTIONED MEASURABLE OUTCOMES, I WILL SKIP THIS PART AND GO TO THE BROAD AND SIGNIFICANT IMPACT. AGAIN, ASPIRE WILL ACCELERATE DRUG DISCOVERY AND DEVELOPMENT AND MAKE THE PROCESS MORE COST EFFECTIVE. WHEN IT COMES TO DISEASE RELEVANCE, ASPIRE RELEVANT ACROSS MANY DISEASES. I WOULD LIKE TO MENTION THAT WE ARE PRESENTING THIS CONCEPT TO YOU TODAY, BECAUSE WE WOULD LIKE TO HAVE IT READY, IF THERE'S AN INCREASE IN APPROPRIATION TO CAN. THANK YOU. >> THE LAST TWO ARE TISSUE CHIP PROGRAMS THAT DAN IS GOING TO GO OVER. >> GOOD MORNING. THIS IS CONCEPT CLEARANCE FOR TISSUE CENTERS, A REISSUE. TO GIVE YOU BRIEF BACKGROUND, TISSUE CHIP PROGRAM IS A PROGRAM THAT SEEKS TO DEVELOP BIOENGINEERED MICROFABRICATED DEVICE THAT MIMICS FOR THE PURPOSE OF TESTING FOR EFFICACY AND SAFETY OF PHARMACOLOGIC AGENTS. THIS IS THE PROGRAM THAT WAS STARTED BACK IN 2012, IN FACT THE FIRST PROGRAM AND FOR A WHILE THE ONLY PROGRAM THAT WAS SUPPORTED BY THE CURES ACCELERATION NETWORK, 2012 TO 2017. WE HAVE SET UP A TISSUE CHIP TESTING CENTER BECAUSE THE TISSUE CHIP DEVELOPERS HAVE BEEN SUCCESSFUL IN DEVELOPING ORGAN CHIPS FOR VARIOUS SYSTEMS IN THE BODY. BUT THE MAJOR INPUT COMING IN FROM THE FIELD IS, AS CHRIS MENTIONED, NCATS DOESN'T DO ANYTHING WITHOUT PARTNERSHIP, SO OUR CURRENT PARTNERS WITH THE TESTING CENTERS WOULD BE THE CONSORTIUM AND FDA INFORMING US WHAT IT TAKES TO BE ABLE TO MAKE THIS TOOLS, THE TISSUE CHIPS BE ADAPTED BY THE COMMUNITY AND PRIMARILY INDEPENDENT VALIDATION. SO THE TESTING CENTERS WAS REALLY SET UP BY NCATS A YEAR AGO TO BE INDEPENDENT AS A PILOT, TO BE INDEPENDENT VALIDATORS OF THIS TECHNOLOGY. AND THEN RECENTLY WE HAVE ALSO BEEN FORTUNATE TO MOVE INTO THE NEXT PHASE OF THE PROGRAM FOR DEVELOPING TISSUE CHIPS FOR DISEASE MODELING AND EFFICACY TESTING. SO FOR THE GOAL OF THIS REISSUE TO EXPAND THE NUMBER OF TESTING COMPOUNDS, SUGGESTED BY THE IQ CONSORTIUM, AND EXPAND THE NUMBER OF PLATFORMS TO BE DEVELOPED. THE CURRENT TESTING CENTER IS ONLY LIMITED TO TESTING PLATFORMS THAT HAVE BEEN SUPPORTED BY NIH, AND SINCE 2012 THE FIELD HAS TREMENDOUSLY GROWN, BOTH IN THE UNITED STATES AND WORLDWIDE, SO THERE'S NOW AN INCREASED DEMAND FROM A NUMBER OF DEVELOPERS TO HAVE PLATFORMS BE TESTED BY OUR TESTING CENTERS. SO THIS WOULD ACTUALLY IN SOME WAYS BRING STANDARDIZATION AND UNIFORMITY INTO THE FIELD, NOT ONLY IN TERMS OF THE BIOENGINEERED PLATFORMS BUT ALSO IN TERMS OF HOF ASSAYS AND THE TYPE OF BIOMARKERS ARE NEEDED TO ASSESS SAFETY AND ETCH CAYS. OF EFFICACY. TO GIVE YOU AN IDEA OF ACTIVITY, THE FIRST PUBLICATIONS COMING OUT OF THE CURRENT TESTING CENTERS WILL BE COMING OUT IN A COUPLE OF MONTHS. AND THAT WOULD BE FOR THE KIDNEY PROXIMAL TUBULE AND THAT SHOULD BE COMING OUT SOON AND THEN ANOTHER ONE FOLLOWING THAT WOULD BE THE BLOOD-BRAIN BARRIER. SO WE ARE EVEN WITHIN THE LAST 6 OR 8 MONTHS AT THE TESTING CENTER THAT'S BEEN IN EXISTENCE, IT'S ALREADY BEEN PRODUCTIVE AND PRODUCING PUBLICATIONS THAT ARE MAKING THIS INFORMATION PUBLICLY AVAILABLE. THE IMPACT OF THIS TESTING CENTER TO VALIDATE THE CHIPS, CERTAINLY ADVANCE NCATS MISSION OF DEVELOPING NOVEL AND INNOVATIVE TECHNOLOGIES TO ADVANCE DIRECT DEVELOPMENT. AND OF COURSE ALSO CONGRUENT WITH NIH EFFORTS FOR REPRODUCIBILITY AND RIGOR. IN TERMS OF EVALUATING SUCCESS OUR ULTIMATE GOAL TO HAVE WIDESPREAD USE AND ADOPTION OF TISSUE CHIP TECHNOLOGY FOR PREDICTIVE TECHNOLOGY AND EFFICACY ASSESSMENT OF CANDIDATE DRUGS. MAJOR OBSTACLE TO ADDRESS AT THIS POINT IS REALLY STILL THE LACK OF PREDICTIVE TOOLS. I THINK THIS IS THE -- THE PROGRAM HAS BEEN IN EXISTENCE FIVE YEARS, WE'RE IN THE CUSP OF BEING ABLE TO LOOK AT CHIP DATA, IN TERMS OF PRE-IND SUBMISSIONS FOR EXAMPLE GOING TO FDA, DEMONSTRATION THAT THE CHIP TECHNOLOGY WOULD BE USEFUL FOR DRUG DEVELOPMENT AND WOULD ADDRESS THIS OBSTACLE OF LACK OF PREDICTIVE TOOLS. IN TERMS OF WHAT HAS BEEN FUNDED WITH THIS TESTING CENTERS, TWO INDEPENDENT TESTING EXPRESSER, ONE TESTING CENTERS, M.I.T. AND TEXAS UNIVERSITY, A DATABASE AT THE UNIVERSITY OF PITTSBURGH, AGAIN A PUBLICLY AVAILABLE WEBSITE AND YOU'RE WELCOME TO LOOK THROUGH IT. AS MENTIONED BY DODA, THE MAJOR FUNDING OF THIS EFFORT HAS BEEN COMING THROUGH THE CURES ACCELERATION NETWORK, IN THE PAST THE CAN REVIEW BOARD INSTITUTED SOME PROJECT CRITERIA IN TERMS OF WHAT CONCEPTS CAN BE FUNDED THROUGH CAN, ONE IS COLLABORATIVE, THIS IS DEFINITELY A VERY COLLABORATIVE ENDEAVOR, WITH NCATS PARTNERING WITH PHARMA AND WITH THE FDA, AND ALSO WITH THE NUMBER OF INSTITUTES AND CENTERS AT THE NIH. IN TERMS OF OUTCOME, OF COURSE WE'RE HOPING THAT THIS WILL LEAD TO THE BETTER SAFETY AND EFFICACY DATA, COMING OUT THROUGH CHIP DATA, WIDESPREAD USE AND ADOPTION OF THE TECHNOLOGY, AND IN PREVIOUS PRESENTATIONS BY TISSUE CHIP INVESTIGATORS, WE HAVE ALREADY SHOWN THAT NUMBER OF SPINOFF COMPANIES HAVE COME OUT TO COMMERCIALIZE THESE PRODUCTS AND SOME OF THOSE ARE ACTUALLY COMING ONLINE SO YOU CAN ACTUALLY START PURCHASING THE CHIPS. FOR BROAD IMPACT, AGAIN, PRIMARILY I'LL FOCUS ON POTENTIAL SAVINGS IN TIME AND COST FOR DRUG DEVELOPMENT. AND THEN DISEASE RELEVANCE, CHIPS ARE CERTAINLY APPLICABLE TO HOST HUMAN DISEASES AND CONDITIONS. WITH THAT THEN I'LL MOVE INTO THE NEXT CLEARANCE, TISSUE CHIP RELATED, THIS TIME A BIT MORE OUT OF THIS WORLD APPLICATION, SO TO SPEAK. THIS IS AN NIH CASE, FOR THOSE WHO ARE NOT FAMILIAR, CENTER FOR ADVANCEMENT OF SCIENCE IN SPACE. THIS IS COORDINATED PROGRAM WITHIN NIH AND USE OF TISSUE CHIP TECHNOLOGY TO ADVANCE TRANSLATIONAL RESEARCH IN SPACE. SO BY BACKGROUND, THE SPACE STATION IS A DESIGNATED NATIONAL LABORATORY BY THE UNITED STATES, UNMATCHED RESEARCH OPPORTUNITIES AND RESOURCES, TO STUDY, FOR EXAMPLE, ACCELERATED HUMAN PHYSIOLOGICAL CHANGES UNDER MICROGRAVITY, ESPECIALLY SIMILAR TO EXHILARATED AGING EFFECTS. SO THIS HAS BEEN A PRODUCTIVE PARTNERSHIP, RESULTING IN 501 AWARDS TWO MONTHS AGO. AND SO THE QUESTION MIGHT BE WHY ARE WE COMING BACK FOR ANOTHER CONCEPT CLEARANCE. THIS IS ANOTHER REISSUE PROGRAM THAT'S BEEN, YOU KNOW, OVERWHELMED WITH A NUMBER OF APPLICATIONS WE RECEIVED THAT ARE CERTAINLY SCIENTIFICALLY INTERESTING AND ADDRESSES A NUMBER OF CHALLENGING QUESTIONS, IN TERMS OF HUMAN PHYSIOLOGY AND OPPORTUNITIES TO ADDRESS NOT ONLY AGING BUT STEM CELL DEVELOPMENT AND DEVELOPMENT OF NEW THERAPEUTICS, TO DEVELOP TISSUE CHIP TECHNOLOGY AT THE INTERNATIONAL SPACE STATION BUT THE ONE THAT I'M REALLY KEEN ON IS LOOKING AT A CHIP. THIS IS WHAT A CHIP LOOK LIKES, THIS IS A KIDNEY CHIP, MINIATURIZED AND SMALL. IF YOU CAN IMAGINE MICROFLUIDIC CHANNELS, SENSORS, CONTROLLERS, ALL SUPPORTING THE SMALL CHIP, WHICH IS PROBABLY THE SIZE OF HALF YOUR LABORATORY. IN PARTNERSHIP WITH THE SPACE ENGINEERS AT NASA, WHO ARE USED TO REDUCING COMPLEX PLATFORMS INTO VERY REDUCED PLATFORM, WE ARE ACTUALLY IN THE POSITION TO EVOLVE TISSUE CHIP TECHNOLOGY TO BE HIGHLY AUTOMATED, REDUCE FOOTPRINT AND ESSENTIALLY TURNKEY TECHNOLOGY. BECAUSE UP IN SPACE ASTRONAUTS ARE NOT SCIENTISTS. I MEAN THEY ARE VERY GREAT INDIVIDUALS BUT THEIR SCIENCE BACKGROUND IS PROBABLY MORE OF PUSH-BUTTON TECHNOLOGY TO TURN ON THE MACHINE AND WATCH IT. PARTNERS WITH SPACE ENGINEERS IN TERMS OF REALTIME READOUTS, ENGINEERING, INTO A BENCHTOP MODEL, TWO BY TWO MODEL. SO INSTEAD OF INVESTING ANOTHER 10, 15 YEARS OF MONEY, THIS WILL ACTUALLY ACCELERATE TISSUE CHIP TECHNOLOGY. IN TERMS OF OUTCOME AGAIN WE'RE LOOKING AT A NUMBER MUCH DIFFERENT HUMAN CONDITIONS, FOR THIS REISSUE. WE HAVE A NUMBER OF PROJECTS ALREADY BEEN AWARDED, FIVE PROJECTS IN FACT ANNOUNCED AT THE NCATS WEB PAGE A MONTH OR SO AGO. POTENTIAL IMPACT AGAIN WOULD BE TO IDENTIFY NOVEL TARGETS FOR DISEASE INTERVENTION, STUDY OF MICROGRAVITY. THERE ARE MOLECULAR SIGNATURES WE HOPE TO CAPTURE IN TERMS OF ACCELERATED AGING DUE TO MUSCLE WASTING, REDUCED CARDIOPULMONARY FUNCTION, IMMUNODEFICIENCY, EVEN KIDNEY STONES. IN TERMS OF EVALUATING SUCCESS, WE HOPE TO BE ABLE TO AGAIN GET THE INFORMATION IN TERMS OF SIGNATURES, WHAT ARE THE MOLECULAR AND EPIGENE OMIC CHANGES THAT SERVE TO USE ON EARTH. WE'RE TRYING TO USE THE CAPABILITIES OF THE SPACE ENGINEERS AND THE INSTRUMENTATIONS THAT WOULD MAKE TISSUE CHIP TECHNOLOGY MUCH MORE WIDELY USED INSTRUMENT ON EARTH. IN TERMS OF BRIEF SUMMARY, WE'VE HAD SUCCESSFUL FUNDING AGAIN NCATS THROUGH CURES ACCELERATION NETWORK, COMMON FUND, AND FIVE PROJECTS HAVE RECENTLY BEEN AWARDED AS OF LAST MONTH THROUGH THIS PROGRAM. AGAIN, AS PART OF THE CAN PROJECT CRITERIA, PROPOSED INITIATIVE WILL CONTINUE CORE RESOURCING OPPORTUNITIES WITH NASA AND CASIS AS WELL AS PHARMA, SO THE ENGAGEMENT IS THAT WE DEVELOP DISEASE MODELS UP IN SPACE AND PHARMA WILL COME IN AND TEST SOME CANDIDATE DRUGS DURING THE PROGRAM. IN TERMS OF OUTCOME ALWAYS LOOKING FOR BETTER DISEASE MODELS, IDENTIFICATION OF NOVEL TARGETS FOR INTERVENTION, AND TRANSFORMATION OF TISSUE CHIP TECHNOLOGY TO TURNKEY TECHNOLOGY. I WON'T GO INTO THE BROAD AND SIGNIFICANT IMPACT BECAUSE I'VE MENTIONED THAT BEFORE AND DISEASE RELEVANCE, IT'S ALL SOMETHING THAT IS APPLICABLE TO A HOST OF HUMAN DISEASES, CONDITIONS, ESPECIALLY THOSE WITH AGING. AND THANK YOU FOR YOUR ATTENTION >> NOW WE'LL TURN IT OVER TO ANNA WHO WILL DO THE LOGISTICAL PART AND DISCUSSION. >> ALL RIGHT. NEXT WE'RE GOING TO DISCUSS EACH OF THE CONCEPTS. WE'RE GOING ASK THE DISCUSSANTS TO SAY A FEW WORDS AND CALL FOR A VOTE OF EACH ONE. WE'RE DOING IT THIS WAY SO WE CAN BE SURE WE COVER EVERYTHING IN THE TIME ALLOTTED. SO THE FIRST CONCEPT IS RARE DISEASES CLINICAL RESEARCH NETWORK PROGRAM, OUR DISCUSSANTS ARE RON BARTEK, (INDISCERNIBLE) AND SHAHKAR. >> DISCLAIMER, THE DISEASE I REPRESENT IS NOT INVOLVED WITH THE RDCRN. I GET THE PRIVILEGE OF SERVING ON THE RDCRN DSMV SO IT'S BEEN A THE LAST FIVE OR SIX YEARS DOING THAT. CHRIS CHARGED US WITH MAKING RECOMMENDATION AS TO WHETHER THESE CONCEPT CLEARANCE PROGRAMS ARE RECEIVING OR GETTING REASONABLE -- ARE THEY A REASONABLE USE OF THE NCATS RESOURCES. I WOULD SAY THIS RDCRN IS AN EXTREMELY REASONABLE USE OF NCATS RESOURCES, RECEIVING UNREASONABLE AMOUNT OF THOSE RESOURCES. I THINK IT'S A WONDERFUL PROGRAM AND I KNOW OUR CURRENT ADMINISTRATION IN WASHINGTON IS COMING DOWN HARD ON DREAMERS SO AT THE RISK OF BEING DEPORTED AS A DREAMER LET ME JUST ASK IF WE COULD CONSIDER ADDING ADDITIONAL RESOURCES TO THIS PROGRAM, AND HELPING IT GROW INTO WHAT I WOULD CALL A MODEL CLINICAL NETWORK THAT IS TRULY COLLABORATIVE, FULL OF TRUE DATA SHARING, AND DEVELOPING NATURAL HISTORY STUDIES THAT ARE ABSOLUTELY ESSENTIAL TO THESE RARE DISEASES THAT HAVE NO OTHER WAY OF DEVELOPING THEM. AND TRUE MODELS TOO OF PATIENT ENGAGEMENT FROM BEGINNING TO END. AND PATIENT ENGAGEMENT FROM BEGINNING TO END AND NATURAL HISTORY DATABASES HAVE BECOME THE HOLY WRIT OF RARE DISEASE DEVELOPMENT, I WOULD EVEN SAY COMMON DISEASE DEVELOPMENT. AND BY DOING SO WE COULD PROVIDE A MODEL OF SUCH A TRULY COLLABORATIVE PATIENT-ENGAGED NETWORK, AND AVOID SOME OF THE ISSUES THAT WE'RE SEEING AND DISCUSSING IN THE CTSA, SO I WOULD SAY 1.$25 MILLION PER CONSORTIUM IS NOT ENOUGH. DEVELOPING THIS MODEL, WE ALSO CAN EMPOWER THESE RARE DISEASES TO BECOME REAL MAGNETS FOR ATTRACTING INDUSTRY PARTICIPATION. THESE INDUSTRIES ARE NOT GOING TO PICK UP AND TRY TO DEVELOP THERAPIES FOR RARE DISEASES THAT DO NOT HAVE SOLID PATIENT INVOLVEMENT AND MORE IMPORTANTY EVEN NATURAL HISTORY STUDIES THAT CAN HELP THEM DESIGN CLINICAL TRIALS AND ADVANCE CLINICAL DEVELOPMENT. I THINK THIS IS A WONDERFUL PROGRAM WITH REAL POTENTIAL FOR ACCOMPLISHING A GREAT DEAL AND WE SHOULD CONSIDER. >> FULL DISCLOSURE, MY DAUGHTER PARTICIPATE IN A FIVE-YEAR NATURAL HISTORY STUDY, IT'S BEEN A PHENOMENAL EXPERIENCE. THE COLLABORATION STARTED IN THE BEGINNING, OUR FOUNDATION WENTS TO THE RESEARCHERS AND CONVINCED THEM THIS WOULD BE WORTH THEIR TIME AND EFFORT. AND WHEN YOU TAKE THE DOLLARS AMOUNTS THAT RON DISCUSSED AND DIVIDE BETWEEN THREE DISEASES OVER FIVE YEARS OVER TEN SITES, IT'S NOT REALLY A LOT TO WORK WITH. THE COLLABORATION STARTED WITH FOUR DIFFERENT NIH INSTITUTES FUNDING THIS, NOT JUST ONE OR TWO. AND I'VE SEEN FIRST HAND THE TRAINING THAT GOES ON, INNOVATION, ALTHOUGH OURS IS A NATURAL HISTORY STUDY WE'VE ALSO DEVELOPED BIOMARKERS AND GONE FAR BEYOND THE ORIGINAL DESCRIPTION. THE SUCCESS OF EARLY ENROLLMENT AND BIOMARKER STUDIES AND WE'VE EVEN EXPANDED THE NUMBER OF SITES BECAUSE OF THE INFRASTRUCTURE THAT CREATED THIS CHANNEL, AND HAS ALLOWED FOR ADVOCACY ORGANIZATIONS ACTUALLY TO ALSO CONTRIBUTE ADDITIONAL FUNDS WHICH HAS MADE A HUGE DIFFERENCE. FAMILIES ARE HAPPY. RESEARCHERS ARE HAPPY. AND AT THE END OF THE FIVE YEARS WE MOST CERTAINLY WILL HAVE A CLINICAL TRIAL NETWORK THAT INDUSTRY COULD MAKE USE OF. I HAD FIRST HAND INTERACTION WITH THE DATA CENTER DOWN IN FLORIDA, AS THE P.I. OF OUR PATIENT-REPORTED REGISTRY. WE'VE TALKED ABOUT LINKING WHAT OUR FOUNDATION HAS COLLECTED IN OUR DATABASE WITH WHAT THE CLINICIANS HAVE COLLECTED, SO THERE'S AN ENDLESS AMOUNT OF COLLABORATION THAT'S BEEN GOING ON AND DITTO TO WHAT HE SAID. >> WELL, I'VE ARGUED HERE BEFORE THAT THIS PROGRAM IS A TRUE GEM THAT DOES SO MUCH WITH SO LITTLE, AND IS A PERFECT FIT FOR THE CTSA PROGRAM TO SOMEHOW BECOME ENGAGED, AND WE'VE GOT TO FIGURE OUT A WAY TO MAKE THE CTSA PROGRAM, ALL THE FUNDING AND INFRASTRUCTURE WE PUT INTO THE CTSAs SOMEHOW BECOME CONNECTED TO THIS, RELATIVELY AND UNDERFUNDED BY INCREDIBLY EFFECTIVE ORGANIZATION. I MEAN, YOU'VE ALREADY CHANGED 50,000 LIVES WITH SO LITTLE MONEY, AND I THINK WE CAN DO A LOT MORE. I KNOW THERE ARE LOTS OF ADMINISTRATIVE CHALLENGES, LOTS OF FUNDING BUCKETS AND WHAT NOT, BUT SOMEHOW WE HAVE TO COLLECTIVELY FIGURE OUT HOW TO MAKE THIS WORK. SO THAT'S MY COMMENT. >> ANOTHER DISCLAIMER, THESE COMMENTS WERE NOT COORDINATED IN ADVANCE. [LAUGHTER] >> YEAH, AND FINAL DISCLAIMER, I DO NOT WORK IN RARE DISEASES BUT I THINK THIS IS A FANTASTIC OPPORTUNITY FOR ALL OF US, YEAH >>> I THINK THE COMMENTS ARE GREAT, THIS IS A REALLY IMPORTANT THING TO SUPPORT. I HAVE A TECHNICAL QUESTION THOUGH. AT THIS STAGE OF RARE DISEASE, KNOWLEDGE DEVELOPMENT PHASE, I'M TRYING TO UNDERSTAND WHAT NCATS' ROLE IS FOR THAT. ICs DEVELOP KNOWLEDGE A LOT. IS THERE A STRATEGY TO GET TRANSLATION MOVES, SHOULD WE'VE AN OUTLINE? THAT'S THE CONTRIBUTION OF NCATS TO SIGH WHAT IS -- SAY WHAT IS THE FIVE-DAY-YEAR GOAL FOR IMPACT ON PATIENTS, BRING INDUSTRY IN TO DO, FIRST INTERVENTION TO RANDOMIZE, NOT SAYING COLLECTION OF DATA AND COLLECTION OF REGISTRIES IS NOT HAVE CRITICAL TO THE FOUNDATION BUT WHAT IS THE TRANSLATIONAL STRATEGY? >> I'D SAY THAT THESE NATURAL HISTORY STUDIES ARE AN EXTREMELY VALUABLE EXPRESSION OF TRANSLATIONAL SCIENCE. I DON'T SEE BEING ABLE TO TRANSLATE THE BASIC SCIENCE OF THESE RARE DISEASES INTO CLINIC WITHOUT REAM SOLID -- REALLY SOLID ROBUST NATURAL HISTORY STUDIES AND I DON'T SEE BEING ABLE TO TRANSLATE THEIR EFFORTS INTO INDUSTRY SUPPORT WITHOUT THOSE SAME DATABASES. SO I THINK NATURAL HIT STUDIES THEMSELVES ARE TRANSLATIONAL SCIENCE >>> THANK YOU, RON. IN ADDITION THERE'S A LOT THAT BE TRANSLATED FROM RDCRN OUTWARD TO OUR PART OF THE NETWORK. THERE'S PROCESS AROUND PULLING THE COLLABORATIVE RESEARCH TOGETHER, AND WHAT ARE THE STEPS TO BRING TOGETHER RESEARCH WHICH OFTEN STARTS FROM VERY LITTLE OR ALMOST NOTHING TO ENGAGING THE RARE DISEASE BOTH PATIENTS BUT AT THE CENTERS THEMSELVES INTO CLINICAL TRIALS AND CLINICAL RESEARCH. SO WE'RE TRYING TO DO EXACTLY WHAT YOU'RE SAYING, WE HAVE 20 MILLION PIECES OF DATA AT RDMCC TO TAKE A CLOSER LOOK AND SEE HOW TO TRANSLATE THIS OUT TO OTHER RARE DISEASES BEYOND THE ONES WE HAVE IN OUR NETWORK SO THERE'S A LOT OF OPPORTUNITY FOR LEARNING THERE. >> SO WHEN WE GET TO A POINT WHERE ONE OF THESE RARE DISEASES ARE READY FOR PILOT PROTOCOL, MY QUESTION IS HOW AND WHO DO WE REQUIRE PARTNERSHIP FOR RECRUITMENT OF PATIENTS WITH THE RARE DISEASES? FOR EXAMPLE, DO WE LOOK FOR PATIENTS THROUGH MEDICAID DATABASES, THROUGH INSURANCE COMPANY CLAIM FORMS OR REGISTRIES? THE REASON I ASK THIS IS BECAUSE MANY OF THE RARE DISEASES OF COURSE RACE AND ETHNICITY AND GENDER ARE SORT IMPACT THE DISEASE, DISEASE DETERMINED THROUGH THAT BUT WHEN WE START GETTING TO GEOGRAPHICAL DIVERSITY, WHERE PEOPLE ARE GOING TO BE CONCENTRATED WHO ARE GOING TO BE ABLE TO HAVE ACCESS TO THESE PILOTS, SO DO WE HAVE THAT AS PART OF THE CRITERIA FUNDING WHEN WE GET TO THE POINT OF PILOT THAT WE'RE ENSURING THAT LEVEL OF DIVERSITY AND INCLUSION? >> I DON'T BELIEVE THAT WE HAVE IT AS SPECIFIC AS THAT, BUT WHAT TENDS TO HAPPEN WITH RARE DISEASES IS THERE'S OFTEN ONLY A FEW EXPERTS IN THE DISEASE LOCATED AROUND THE COUNTRY OR INTERNATIONALLY AS WELL. WE ALSO HAVE INTERNATIONAL SITES. BUT THAT'S PART OF THE INTENT BEHIND BUILDING THE NETWORK IS THAT YOU CAN GEOGRAPHICALLY DISPERSE THE CENTER SO PATIENTS FROM AROUND THE COUNTRY WOULD BE ABLE TO FIND A CENTER OR AN AREA OF EXPERTISE THAT ISN'T SO FAR SITUATED. SOME THINGS WE'VE TALKED ABOUT EXPERIMENTING WITH ALSO THOUGH IS GIVEN THE SMALL NUMBER OF CENTER AND EXPERTS CAN WE LEVERAGE TELEMEDICINE OR SOME REMOTE TOOLS WHICH WOULD JUST BE SUCH A PERFECT FIT FOR RARE DISEASES FOR EXACTLY THE REASONS THAT YOU STATE. >> I WOULD DEFINITELY LIKE TO SEE THIS AS AN EMPHASIS AS WE LOOK TO THIS PARTICULARLY BECAUSE THERE'S A LOT THAT WOULD HAVE GONE LOOKING AT THE NATURAL HISTORY TO THE POINT WHERE YOU GET TO THE PILOT STUDY, AND SO I THINK THAT AS THE WAY WE'RE SEEING TELEMEDICINE EVOLVE WE OUGHT TO MAKE THIS PART OF THE CRITERIA. >> THANK YOU. I WANT TO MAKE THE COMMENT SOME OF THE CONSORTIA OF RDCRN PROGRAM, THEY DO TRAVEL CLINICS TO TAKE CARE OF THOSE PATIENTS WHO CANNOT TRAVEL OR THERE ARE NO EXPERT CENTERS. >> COULD YOU IDENTIFY YOURSELF? >> RASHWINGA (INDISCERNIBLE), PROGRAM DIRECTOR FOR RDCRN. >> A QUICK POINT, ANOTHER ASPECT OF THIS PROGRAM THAT WILL HELP ADDRESS YOUR ISSUE IS THERE'S A WONDERFUL DEGREE OF ENGAGEMENT BY PATIENTS AND PATIENT ADVOCACY ORGANIZATIONS. THERE'S AN OVERALL COLLABORATIVE PATIENT ADVOCACY GROUP FOR THE WHOLE RDCRN AND FOR EACH CONSORTIA THERE ARE MULTIPLE PATIENT ADVOCACY GROUPS AND THEY ARE ABSOLUTELY DEDICATED TO FINDING EVERY PATIENT IN THEIR DISEASE, REGARDLESS OF RACE, GENDER, GEOGRAPHIC DISTRIBUTION, THEY WANT TO KNOW WHERE EVERY PATIENT IS AND RECRUIT EVERY ONE OF THEM INTO THESE PILOT STUDIES. >> ONE MORE RESPONSE FROM PROGRAM AND THEN A COUPLE MORE QUESTIONS OVER HERE STARTING WITH SHARON AND THEN WE'LL CALL FOR A VOTE FROM OUR FULL MEMBERS ON THIS CONCEPT. >> JUST WANT TO BRIEFLY ADD TO THE COMMENT EARLIER THAT I THINK THIS IS ONE OF THE OPPORTUNITIES WHERE THE CTSA PROGRAM CAN CONNECT TO RARE DISEASES. YOU HEAR THIS AFTERNOON ABOUT THINGS LIKE THE IRB STREAM LINED MODELS THAT SOMEHOW ALLOW US TO HAVE JUST-IN-TIME SITES TO BE RESPONSIVE TO WHERE THE PATIENTS ARE. RIGHT NOW WE CAN'T REALLY DO THAT EASILY BECAUSE THE COST AND DELAY AND ACTIVATION ENERGY TO OPEN UP A SITE IS JUST PROHIBITED >> YEAH, SO I'M SUPPORTIVE MUCH THIS AND AGAIN DISCLAIMER FROM ME AS MY RARE DISEASE IS NOT INVOLVED, ONE OF THE THINGS I WONDER IS WHEN CAN WE START TO PUT REQUIREMENTS ON THE PROGRAM SUCH THAT FOR EXAMPLE MY ENCOUNTERS WITH INVESTIGATORS WORKING IN THE NETWORK ARE TYPICAL SO THEY DON'T WANT TO SHARE DATA, THEY WAIT UNTIL SOMETHING'S PUBLISHED, THEY ARE RETARDING SOME THINKS WE WANT TO DO MORE GLOBALLY IN THE NATION AND BEYOND BECAUSE THEY BEHAVE AS TYPICAL SCIENTISTS. I TOTALLY GET THAT. IT'S BACK TO THE IOM REPORT, LET'S STOP USING PUBLICATIONS AND PROMOTIONS AS BENCHMARKS. BUT, YOU KNOW, YOU GUYS ARE THE FUNDERS AND OVERSEE THIS THING. IT'S TIME FOR NIH OVERALL, MAYBE THIS IS A GREAT PLACE TO START, YOU HAVE TO SHARE THESE DATA. YOU HAVE TO SHARE THESE METHODS. WE SHOULDN'T BE ABOUT JUST A HAND FULL OF SMALL DISEASES, WE SHOULD RAISE THE BAR AND GET IT DONE. PEOPLE ENGAGING, I DON'T LIKE THE WORD PATIENT, I DON'T SEE ANYTHING EXTRAORDINARY EXCEPT IN SMALL POCKETS OF EXTRAORDINARY WITHIN THE NETWORK, AGAIN MODERATELY TYPICAL NOT REALLY SAVVY ENGAGEMENT BUT A LITTLE BIT OF THE NETWORK THAT I'VE SEEN. I'VE SEEN IT OVER THE YEARS, I'VE BEEN AND ADVISER, THEY DON'T CALL ON ME A LOT BUT I REALLY APPRECIATE IT BUT I THINK IT'S TIME FOR TO US REALLY START TO MAKE A DIFFERENCE OR WE'RE GOING TO HAVE THE SAME CULTURE FOREVER. >> SO I AGREE. THIS IS A FANTASTIC INITIATIVE, NATURAL HISTORY STUDIES ARE EXTREMELY IMPORTANT FOR THE TRANSLATION, BUT THE OTHER SIDE OF IT IS HAVING PATIENT DERIVED MATERIALS INCLUDING SOMETHING THAT COULD FEEDBACK INTO iPS SUBTIMES, COMBINING TWO INITIATIVES WE HEARD TODAY I'M TRYING TO FIGURE OUT IS THERE CROSS-TALK WHERE YOU'RE INFORMING THE iPS SYSTEMS AND ENABLING SOME KIND OF TARGET AND DRUG DISCOVERY ASPECT. MAYBE I MISSED IT IN THE PRESENTATION. >> IT WASN'T IN THE PRESENTATION BUT THAT'S GOING ON. WE DO HAVE A NUMBER OF CENTERS, NOT ALL BUT A NUMBER ARE PARTICIPATING WITH DAN'S TISSUE CHIP PROGRAM, THAT'S SOMETHING WE'D LIKE TO GROW AS WELL. >> ALL RIGHT. WITH THAT I THINK IT'S TIME TO ASK OUR FULL MEMBERS FOR VOTING, DO I HAVE A MOTION? >> SO MOVED. >> SECOND? AND ALL IN FAVOR? >> AYE. >> I'M SO SORRY. WITH THAT CONCEPT ONE IS APPROVED, LET'S MOVE TO CONCEPT TWO, ALLEN PALKOWITZ WHO I HOPE IS STILL ON THE PHONE >> YES, I AM. >> WONDERFUL. AND LYNN. >> ALLEN, GO AHEAD >> I'LL GO AHEAD. THANK YOU VERY MUCH. I HAVE HAD A FAIR AMOUNT OF EXPERIENCE IN THIS SPACE DURING MY TIME AT LILLY FOR THE PAST 12 YEARS OR SO WE'VE BEEN WORKING IN THE AREA OF AUTOMATED CHEMICAL SYNTHESIS AS A KEY RESOURCE AND CAPABILITY TO PARTNER WITH OUR SCIENTISTS TO ADVANCE MANY OF OUR EFFORTS IN DRUG DISCOVERY. THIS IS A TECHNOLOGY THAT HAS EVOLVED SOMEWHAT, BUT STILL HAS A LONG WAY TO GO. AND FULL DISCLOSURE WE ARE BUILDING A NEW SYSTEM WHICH I WOULD CHARACTERIZE AS SECOND GENERATION SYSTEM AT OUR FACILITY IN SAN DIEGO THAT IN MANY CASE BEGINS TO KIND OF TAKE SOME OF THE EXCITING LEAPS THAT ARE PART OF THIS PROPOSAL. FROM THE BACKGROUND STANDPOINT HAVING WITNESSED HOW THIS TECHNOLOGY COULD ENABLE AND BRING TOGETHER A NUMBER OF KEY CONCEPTS, TO ADVANCE DRUG DISCOVERY, I REALLY SEE SOME VERY NICE PARALLELS OF HOW SUCH A SYSTEM IS BEING ENVISIONED COULD ACTUALLY ADVANCE THE MISSION OF NCATS AND REALLY THE BROADER MISSION OF NIH BY BEING ABLE TO CREATE A VERY FORWARD-LOOKING RESOURCE TO AGAIN EXPAND ACCESS TO CHEMICAL DIVERSITY, TO ADVANCE INTERROGATION OF BIOLOGICAL TARGETS, BUT ALSO TO DO IT IN A WAY THAT BRINGS MORE EFFICIENCY TO THE PROCESS BY LINKING TOGETHER TECHNOLOGIES SUCH AS AUTOMATED SYNTHESIS, COMPUTATIONAL METHODS FOR MOLECULE DESIGN AND BIOLOGICAL TESTING THAT THERE'S A REAL EFFICIENCY THAT CAN BE GAINED TO ACCELERATE THIS WORK AND SUPPORT A NUMBER OF ACTIVITIES IN PARALLEL. THIS IS SOMETHING THAT IS NOT AN EASY UNDERTAKING AND I THINK THE IDEA OF BRINGING TOGETHER A NUMBER OF ACADEMIC COLLABORATORS AS WELL AS INDUSTRY INTERESTS COULD REALLY ADVANCE A LOT OF THE NECESSARY TECHNOLOGIES THAT WOULD ALLOW THIS TO ACTUALLY BE A VERY FORWARD AND PRODUCTIVE PLATFORM THAT CAN BENEFIT FROM ADVANCES IN THE NUMBER OF TECHNOLOGICAL AREAS. AND I THINK IN ADDITION TO SUPPORTING SOME OF THE BROADER MISSIONS OF THE NIH, IT'S ALSO A RESOURCE THAT ACTUALLY CAN BRING IN COLLABORATORS FROM MANY DIFFERENT FIELDS THAT CAN ONLY ADVANCE THE PRIMARY SCIENCE OF CHEMISTRY BUT DIRECTED TO NEW ARES OF BIOLOGICAL INVESTIGATION BY VIRTUE OF THE FACT THAT THE TECHNOLOGY WILL ALLOW THIS SYSTEM TO BE ACCESSED REMOTELY FROM ANYWHERE IN THE WORLD AND ACTUALLY BE SOMETHING THAT COULD BE SHARED IN A VERY DISTRIBUTED WAY. AND THAT'S SOMETHING WE'VE LEARNED ON OUR OWN AS WELL, IN SOME OF THE EARLY VERSIONS OF OUR WORK. I ALSO THINK THAT IT'S A NICE WAY TO DRAW SYNERGY BETWEEN A LOT OF THE INITIATIVES AT NCATS AND HAVING A DISCUSSION ON RARE DISEASE WORK, THERE IS A GREAT POSSIBILITY TO LEVERAGE SOME CAPACITY OF INTEGRATED MOLECULE DESIGN AND BIOLOGICAL EVALUATION TO PERHAPS PROVIDE NEEDED RESOURCE FOR SOME AREAS OF RARE DISEASE RESEARCH THAT COULD BENEFIT FROM THIS KIND OF CAPACITY AND CAPABILITY AND I THINK THERE COULD BE SOME TREMENDOUS SYNERGY TO REALIZE, YOU KNOW, IN TERMS OF BROADENING SOME OF THE BROADER -- THE EXPANDED INITIATIVES OF NCATS AND SOME OF THE BROADER GOALS THAT MANY OF THE INDIVIDUAL PROGRAMS ARE TRYING TO ACHIEVE. I'M VERY SUPPORTIVE. I'VE SEEN THIS PLAY OUT REAL TIME IN THE LIMITED ENVIRONMENT OF OUR COMPANY. SOME ADVANCES BEING PROPOSE AND A WAY TO BRING IN OTHER AREAS OF SCIENCE TO MAKE IT MORE OF AN INTEGRATED, TO TAKE WHAT'S TRADITIONALLY DONE IN A DISTRIBUTED LABORATORY ENVIRONMENT AND TO SOMETHING THAT'S CENTRALIZED HAS A LOT OF GREAT POTENTIAL FOR THE FUTURE AND FOR IMPACT OF THE NCATS MISSION. >> THANKS. LET ME EXPAND ON ALLEN'S COMMENTS. I THINK STARTING AT 100,000 FEET, I DO THINK IT'S IMPORTANT FOR US TO EXPRESS IN MEETING LIKES LIKE THIS AND OTHER VENUES CALL TO HAVE MORE MONEY AND INVESTMENT IN SCIENCE, MACRO LEVEL AT NIH AND NIH TO TAKE SOME OF THOSE FUNDS AND PUT THEM MORE CENTRALLY INTO NCATS BECAUSE OF THE ABILITY TO ENABLE THE AGENDAS OF ALL THE I.C.s, TO GET THAT OUT THERE, CHRIS, SO YOU KNOW I'M VOTING FOR YOU. IN THE SPIRIT OF POKING A SKUNK, YOU PICKED A BIG SKUNK AND INCREDIBLY IMPORTANT SKUNK. IF WE THINK ABOUT WHAT I TALK ABOUT CIRCULARIZING R&D TO LEARN, REITERATE, TAKE LATE STAGE CLINICAL TRIALS TO INFORM PHASE 3 TRIALS TO INFORM PROOF OF TRIALS, SELECTION OF BETTER CHEMICALS WE HAVE TO EXPAND THE CHEMICAL SPACE. WE MADE PROGRESS IN LARGE MOLECULES, MONOCLONAL ANTIBODIES, ET CETERA, I'M AN INFECTIOUS DISEASE FIGURES SO THINK ABOUT THE CHEMICAL SPACE ASSOCIATED WITH PATHOGENS, THEN YOU GOT ANOTHER CHALLENGE THERE IN TERMS OF THAT ABILITY TO DO IT. WE CAN HAVE TARGETS LIKE PHOSPHO-GLYCERATE MUTASE, SINGLE CELL, MANY ARE SINGLE CELL ORGANISMS, YOU CAN SEE THIS OPENS ABILITY TO ADDRESS EACH AND EVERY DISEASE AREA, THIS FULLY MEETS CAN CRITERIA AND I GUESS IF I ONLY HAD ONE COMMENT IT SEEMS LIKE MOST OF THE INFORMATION POINTS TOWARDS EFFICACY BUT I THINK SAFETY CAN BE CHOSEN FROM THESE ITERATIVE LOOPS LOOKING FROM THE CHEMICAL DIVERSITY THAT YOU INCREASE. NOT ONLY JUST JOINING UP IS IT HITTING A TARGET INSIDE OF A CELL BUT ALSO WHAT IS IT DOING TO THAT CELL AND THAT TISSUE FROM A SAFETY POINT OF VIEW SO THAT THE TOXICOLOGY AGAIN INFORMS THE PROGRESS. SO THANK YOU FOR BRINGING IT FORWARD. >> ANY ADDITIONAL COMMENTS OR QUESTIONS? >> I THINK THIS IS REALLY VERY EXCITING. THIS IS AN AREA THAT -- WHEN I WAS AT DARPA, THE (INDISCERNIBLE) PROGRAM CAME ACROSS MY DESK FROM TYLER, I THOUGHT IT WAS A TREMENDOUS OPPORTUNITY TO DO FOUNDATIONAL RESEARCH THAT CROSSES ACROSS DISCIPLINES AND YOU'VE SET THIS UP BEAUTIFULLY. IT'S REALLY GREAT. I THINK THAT THIS IS A PROGRAM THAT'S REALLY -- SHOULD BE HIGHLIGHTED, OUTSIDE THE SCHEME OF TYPICAL BIOLOGY. NIH IS FOCUSED ON BIOLOGY, BLAH, CHEMISTRY, A WONDERFUL THING. I WISH THERE WAS SOMETHING IN PHYSICS BECAUSE WE HAVE TO BRING IN OTHER SCIENTIFIC DISCIPLINES TO CRACK THE NUTS, WE KEEP CHASING THE SAME RAT HOLES BUT WE HAVE TO LOOK TO OTHER SCIENTIFIC DISCIPLINES TO HELP. ONE GROUP YOU DID NOT PUT UP THAT WE SHOULD REACH OUT TO IS ALSO NATIONAL SCIENCE FOUNDATION. THEY PUT A LOT OF MONEY INTO FUNDAMENTAL CHEMISTRY AND WE NEED TO ENGAGE THEM HERE. YOU'RE DOING FUNDAMENTAL SCIENCE AS APPLIED TO BIOLOGY WHICH IS AN APPLICATION WHICH IS AWESOME BUT STILL COMES BACK TO FOUNDATIONAL THINGS. YOU CAN IMAGINE THIS KIND OF CHEMISTRY BEING APPLIED TO ECOLOGIC PROBLEMS, TO OUR ENERGY PROBLEMS. THIS IS FUNDAMENTAL SCIENCE ALTHOUGH IT'S CHEMISTRY AND NOT CLASSICALLY BIOLOGY. I THINK ONE OF THESE THINGS, CHRIS, I APPLAUD WHAT LYNN SAID, YOU HEARD MY WIFE YESTERDAY SHE WANTS TO SEE MONEY FROM OTHER ICs, FROM CMS. WHERE I SIT THIS IS A WONDERFUL PROGRAM, THIS IS A DEPARTURE FROM THE CLASSIC WAY NIH DOES THINGS. OTHER I.C.s WILL NOT EMBRACE THIS AS WELL AS NCATS, THAT'S WHAT WE'RE TALKING ABOUT, OUT OF YOUR COMFORT SPACE TO CHEMISTRY WHICH I JUST APPLAUD. WHO IS THE ORGANIC CHEMIST ON YOUR STAFF? [LAUGHTER] ARE YOU? NO, EXACTLY. SERIOUSLY, WHY DON'T WE HAVE ONE? AND WHERE IS OUR PHYSICIST? AND ON IT GOES. >> I WANT TO MENTION -- (INAUDIBLE). >> SO I THINK FIRST ADDRESSES A BIG ISSUE AROUND CHEMICAL DIVERSITY AND I THINK THAT THAT'S A HUGE ADVANCE. THE ONE THING ALLEN TOUCHED ON, HE MENTIONED THE WORD "EFFICIENCY." I THINK IT WOULD BE REALLY IMPORTANT AS WE START DOWN THIS ROAD TO THINK ABOUT TIME, COST, EFFICIENCY. THERE'S A LOT OF TECHNOLOGY THAT MAY NOT BE EFFICIENT, AND WHAT'S THE BENCHMARK? WE TALKED ABOUT THE NATURAL HISTORY OF RARE DISEASES. WHAT'S THE NATURAL HISTORY, WHAT DO WE KNOW ABOUT WHAT IT WOULD TAKE TO DO THIS THROUGH OTHER MECHANISMS, AND IS THIS JUST A FANCY NEW TECHNOLOGY THAT MAY IN FACT COST MORE OR SLOW US DOWN, BUT REALLY THINK ABOUT THOSE METRICS. >> I THINK DAN MAKES A GOOD POINT. AND THIS IS OBVIOUSLY A HIGH END TECHNOLOGY, SORT OF SETUP. BUT AT THE SOCIALOLOGICAL LEVEL IT'S DEMOCRATIZATION OF MEDICINE OR CHEMISTRY, IT'S WHAT MANY OF YOU REALIZE ESPECIALLY IN RARE DISEASES AND OTHER SPACES, MEDICINAL CHEMISTRY IS A VERY HIGH END SORT OF ENTERPRISE, OFTENTIMES RUN IN LARGE CORPORATIONS, PHARMACEUTICAL COMPANIES, CROs WHO WANT TO ADDRESS BIG PROBLEMS BECAUSE OF THE MARKET, BECAUSE OF THE COST, BECAUSE OF ALL THE WORK THAT NEEDS TO BE DONE. AND THEREFORE IT'S RUN BY VERY BIG CHEMISTS, LEAD CHEMISTS ARE LOTS OF CHEMISTRY RESOURCES WHO BELIEVE THEY ARE LIKE MICHELANGELO OF CHEMISTRY AS OPPOSED TO, YOU KNOW, DEMOCRATIZATION OF CHEMISTRY. HERE I THINK WHAT WILL HAPPEN WITH SOME SYSTEM LIKE THAT I THAT CAN BE REMOTELY MANAGED, THAT ALREADY HAS RESOURCES AT THE DISPOSAL OF ANY GREAT CHEMIST IN THE COUNTRY, ALL YOU NEED IS A VERY SMALL ORGANIC CHEMIST WHO IS VERY INTERESTED IN A DISEASE AND THAT TARGET AND THEY CAN ACTUALLY HAVE THE FULL RESOURCES OF AN ENTIRE LILLY OR AN ENTIRE GLAXOSMITHKLINE. SO I THINK THERE'S SOMETHING MORE TRANSFORMATIVE ABOUT THIS THAN JUST HIGH END FANCY AUTOMATED CHEMISTRY AND STRUCTURAL BIOLOGY. SO I JUST WANT TO ADD THAT COMMENT. >> CALPANA? DAN? ANY OTHER COMMENTS? SOUNDS LIKE THE DISCUSSION IS DONE. DO I HAVE A MOTION TO APPROVE? SECOND? AND VOTES FROM FULL MEMBERS, ALL IN FAVOR? ANY OPPOSED? AND ANY ABSTENTIONS? NOT SURPRISINGLY THAT CONCEPT IS APPROVED. NEXT UP CONCEPT 3 AND THAT IS THE FIRST OF TWO TISSUE CHIP CONCEPTS, BOTH REISSUES AND ASSIGNED DISCUSSANTS ARE ALLEN AND LYNN AGAIN. >> THIS IS ALLEN AGAIN. THANK YOU. AGAIN, I HAVE FOLLOWED THIS AREA QUITE CLOSELY, AND HAVE WATCHED THE EVOLUTION OF THE PROGRAM OVER THE PAST SEVERAL YEARS. REALLY THE GROWING IMPORTANCE THAT THIS TECHNOLOGY WILL HAVE IN REALLY ADDRESSING ONE OF THE KEY TRANSLATIONAL GAPS THAT WE HAVE IN DRUG DISCOVERY ACTUALLY LINKING PRE-CLINICAL OBSERVATIONS TO THE CLINICAL SETTING AND DO THAT IN A WAY THAT IS MORE HIGHLY PREDICTIVE AND ONE THAT COULD BRING IN A TREMENDOUS AMOUNT OF EFFICIENCY, MINIMIZE OUR DEPENDENCE ON ANIMAL MODELS THAT TEND TO BE NOT ENTIRELY PREDICTIVE OR IN SOME CASES COULD BE MISLEADING, WHICH ALSO COULD REALLY HELP REDUCE THE TIME IT TAKES TO GO FROM A CONCEPT TO ACTUALLY MORE EFFECTIVE AND PREDICTIVE HUMAN TESTING. I THINK A LOT OF THE WORK THAT'S GOING ON HERE WILL CONTINUE TO BRING MORE VALIDATION TO THE TISSUE CHIPS AND TO THE VARIOUS SYSTEMS THAT ARE BEING DEVELOPED, AND REALLY BEGIN TO CREATE THAT CONNECTION THAT GIVES CONFIDENCE IN OUR ABILITY TO PUT THIS IN REALTIME PRACTICE INTO ALL KIND OF TRANSLATIONAL SETTINGS WHETHER IT BE IN INDUSTRY, WHETHER IN GOVERNMENT LABS OR OTHER AREAS WHERE THIS KIND OF TECHNOLOGY COULD REALLY HELP BRIDGE UNDERSTANDING OF HUMAN DISEASE INTO A SETTING WHERE WE'RE TRYING TO IDENTIFY THERAPIES OR HELP MAYBE MODEL DIFFERENT DISEASE POPULATIONS AND UNDERSTAND HOW POTENTIAL DRUGS COULD WORK AND MAYBE EVEN UNDERSTANDING A GREATER LEVEL OF SAFETY IN THE RELEVANT TISSUES THAT WILL BE -- THAT ARE GOING TO BE IMPORTANT IN THE LONG RUN. I THINK THERE ARE A NUMBER OF KEY SYNERGIES BETWEEN WHAT DAN OUTLINED FOR THE TWO PROPOSALS. I THINK ONE OF THE KEY CHALLENGES IS GOING TO BE, YOU KNOW, THE CONTINUING PUSHING THE LIMITS OF HOW THESE SYSTEMS CAN BE MADE OPERATIVE, AND MADE EASY TO USE SO I THINK THE CONNECTION WITH NASA PROVIDES A TREMENDOUS CATALYST FOR LOOKING AT MINIATURIZATION OR FINDING WAYS TO MAKE THE SYSTEMS MORE ACCESSIBLE FOR BROADER SCALE AND I THINK WILL THIS FIND ITS WAY INTO HOW THESE CAN BE MADE MORE AVAILABLE TO PRIMARY USERS. SO I THINK FURTHER VALIDATION BUT THEN EXTENDING IT TO SOME OTHER INVESTIGATIONS THAT ARE BEING DISCUSSED I THINK ARE GOING TO CONTINUE TO ACCELERATE THIS PROGRAM FORWARD AND FROM MY PERSPECTIVE, I'VE SEEN INDUSTRY RESPONSE TO THE TISSUE CHIP PROGRAM, VERY FAVORABLE AND NAILS A BIG SWEET SPOT OF TRANSFORMATION OF OUR WORLD AND ONE THAT I THINK GIVEN THE FDA'S INVOLVEMENT AND THEIR COMMITMENT TO PARTNERING COULD BE TRANSFORMATIVE TO HOW WE GET EMERGING CONCEPTS AND THERAPIES TO PATIENTS MUCH QUICKER AND WITH GREATER EFFICIENCY AND HOPEFULLY BETTER PREDICTABILITY OF SUCCESS. >> I'LL COMBINE MY COMMENTS ON BOTH LIKE ALLEN DID AS WELL. AGAIN STARTING AT THE MACRO LEVEL, OUR GRANDKIDS WILLING -- WILL BE SHOCKED TO LEARN WE USED TO USE ANIMALS FOR TESTING TO PREDICT TOXICOLOGY, THEY WILL SAY DIDN'T YOU UNDERSTAND IT WAS POORLY PREDICTIVE, POORLY REPRODUCIBLE AND EVEN IF YOU HAD NO SIGNALS YOU WENT INTO HUMANS AND WERE SURPRISED THERE WAS TOXICITY, SO DAD, GRANDDAD, WHAT WERE YOU THINKING? I THINK THE EXPANSION OF TISSUE CHIPS, ORGAN CHIPS HAS GOT TO BE THE RIGHT WAY TO GO AND IN TERMS OF SOMETHING THAT NCATS AND THE CAN CRITERIA FULLY EXPRESSES HOW THIS IS SOMETHING THAT NOT 50 DIFFERENT DISPARATE GROUPS& ACROSS NIH NEEDS TO ACCOMPLISH. THIS SHOULD BE COORDINATED, CENTRALIZED, COLLABORATIVE AS PART OF THAT SPIRIT. I THINK THE ABILITY AGAIN AS I SAID EARLIER WITH THE CHEMICAL SPACE LOOKING AT AT EFFICACY AND SAFETY, THIS TISSUE CHIP APPROACH ALLOWS YOU TO UNDERSTAND THE HEALTH OF THAT TISSUE AS WELL AS WHETHER OR NOT YOU'RE HAVING A DYNAMIC EFFECT ON THE BIOLOGY. AND THEN AGAIN SOMETHING THAT INDUSTRY WOULD STRUGGLE WITH DOING WITHOUT HELP FROM NCATS IS GOING INTO SPACE OR GOING INTO SPECIAL ENVIRONMENTS SO THAT'S ALSO LINKED UP AND COORDINATED SO WE CAN ANSWER QUESTIONS THAT WE CERTAINLY ARE LIMITED IN TERMS OF BEING HERE UNDER THE NORMAL CIRCUMSTANCES ON EARTH. THE OPPORTUNITY TO GO INTO SPACE AND STUDY THIS I THINK IS EXTRAORDINARILY A POSITIVE LINK TO THIS TECHNOLOGY. SO VERY SUPPORTIVE OF THIS PROPOSAL AS WELL, OR THE TWO PROPOSALS, SORRY. >> ANY ADDITIONAL COMMENTS? JEFF? >> AGAIN, ANOTHER EXCITING AREA. AND I JUST THINK IT CAME OUT OF DARPA. BUT I'M REALLY VERY HAPPY TO SAY THIS IS VERY EXCITING AREA. WE NEED TO PUSH FORWARD IN EVERY WAY POSSIBLE. I WANT TO ECHO WHAT SHARON SAID, THIS IS TIME NOW FOR WHEN ARE WE GOING TO MAKE THE TRANSITION. I MEAN, WHEN IS INDUSTRY GOING TO START TO GET INVOLVED, HOW ARE WE GOING TO START MOVING SMARTLY OUT? I THINK THAT PART OF THIS IS THE ENABLING WAY TO DO IT. IT REALLY IS. BY THE WAY, ONE SMALL THING, I WOULD PROBABLY FIND A DIFFERENT WAY TO CHARACTERIZE. I KNOW A BUNCH OF THESE GUYS, I DON'T THINK YOU WANT TO CHARACTERIZE THEM THE SAME WAY, ASTRONAUTS. >> THANK YOU, JEFF. JUST TO ADDRESS THE QUESTION ABOUT THE COMMERCIALIZATION OR INDUSTRY ADOPTION, SO INDUSTRY HAS BEEN ENGAGED AT THE VERY ONSET OF THIS PROGRAM SO WE HAVE MOUs CAN PFIZER, GHK, ASTRA ZENECA TO PROVIDE TESTING COMPOUNDS. WITH TRAINING CENTERS ONE OF THE POSSIBILITIES IN TERMS OF IMPLEMENTATION OF THIS NEXT GEN TESTING CENTERS IS ACTUALLY TO SPIN IT AS A FEE FOR SERVICE WITH PHARMA BEING ENGAGED IN TERMS OF EVEN TESTING THEIR SET SET OF COMPOUNDS ALREADY USING THAT TYPE OF ENVIRONMENT. IN TERMS OF THE REVISION OF RESOURCES, COMPOUNDS TO TEST, VALIDATION SET OF COMPOUNDS, TYPE OF BIOMARKERS, ASSAYS TO USE FOR TOXICITY OR EFFICACY ASSESSMENTS, THOSE ARE HEAVILY WITH INPUT FROM PHARMA AND FDA. SO FROM THE GET-GO WE ACTUALLY ENGAGE THEM. >> TO ECHO THAT, I THINK IT WAS THE RIGHT IDEA TO INVOLVE FDA EARLY BECAUSE THERE'S THIS AGE OLD CIRCLE OF POTENTIAL USERS, INDUSTRY IN PARTICULAR MAKES TO SAY WE WOULD USE IT IF WE WOULD KNOW IF FDA WOULD ACTUALLY ACCEPT IT. TO THAT END FDA IS CURRENTLY IMPLEMENTING ONE OF THE CHIPS, GUT CHIP, SPECIFICALLY FOR (INAUDIBLE) TO ENGAGE OUR COLLEAGUES AND I BELIEVE THE FUTURE IS VERY BRIGHT AND I THINK WE WILL HAVE IN A FEW YEARS VERY DEFINED AND SPECIFIC CONDITIONS UNDER WHICH WE WILL ACCEPT FROM SPONSORS AND INNOVATORS INFORMATION BASED ON CHIPS, PARTICULARLY AS THOSE ARE BEING MADE MORE ROBUST AND ALSO IMPLEMENTATION PROCESS IN TERMS OF SERVICE, GOOD DIRECTIONS. WE SHOULD CONTINUE THIS AND I THINK IT'S GOING RIGHT. >> YES, WHAT FRANK MENTIONED IS THE CENTER FOR SUPPLEMENTS AND FOOD AND NUTRITION AND FDA, SO THEY ACTUALLY SET UP AN MOU OR CRADA AGREEMENT WITH ONE OF THE SPINOFF COMPANIES TO ACTUALLY TAKE THEIR G.I. ON A CHIP TO START LOOKING AT BIOAVAILABILITY, NOT OF DRUGS BUT IN THIS CASE SUPPLEMENTS, AND BE ABLE TO ADDRESS THOSE KIND OF ISSUES SO IT'S NOT NECESSARILY DRUG DEVELOPMENT POTENTIALLY IMPACT ALSO WITH FOR EXAMPLE ENVIRONMENTAL TOXINS, SO DISCUSSIONS WITH NIEHS AND EPA IN TERMS OF ADOPTION OF THIS TECHNOLOGY, IN THOSE AREAS. >> JUST ONE FINAL COMMENT, BECAUSE ALLEN AND DAN ARE BOTH HOPING IN BIOACCELERATE, THEY ARE IN CONTACT WITH THAT, WHICH IS A MULTI-COMPANY CONSORTIUM THAT THIS IS I THINK THE GREAT GROUP THAT WOULD HOPEFULLY PARTNER WITH YOU ON ADVANCING THIS AS WELL FROM ACROSS THE VARIOUS COMPANIES. >> SEEMS WE HAVE NO ADDITIONAL DISCUSSION. IS THAT RIGHT? ALL RIGHT. IN THAT CASE WE HAVE BOTH CONCEPTS DISCUSSIONED TODAY BUT WE'RE GOING TO VOTE SEPARATELY. THIRD, DO I HAVE A MOTION TO ADVANCE THAT ONE? SECOND? ALL IN FAVOR? ANYONE OPPOSED? ANY ABSTENTIONS? ALL RIGHT. CONCEPT 3 IS CLEARED. LET'S DO CONCEPT 4. DO I HAVE A MOTION? SECOND? ALL IN FAVOR? ANY OPPOSED? AND ANY ABSTENTIONS? ALL RIGHT. SO TISSUE CHIPS IN SPACE CONCEPT IS ALSO CLEARED. AND WITH THAT WE NEED TO MOVE RIGHT INTO OUR NEXT PRESENTATION. >> THANK YOU FOR THOSE DISCUSSIONS. YOU MAY HAVE NOTICED ME TYPING MADLY ON MY IPHONE WHILE I WAS -- I WAS TAKING NOTES ON WHAT YOU ALL SAID AND I KNOW THERE ARE A NUMBER OF OTHER PEOPLE HERE WHO ARE OFFICIALLY TAKING NOTES, SO YOU SHOULD BE ASSURED THAT EVERYTHING YOU SAID WAS CAPTURED AND WILL CERTAINLY BE -- EVERYTHING WE CAN INCLUDE IN THESE -- AS WE MOVE FORWARD TO THESE CONCEPTS OF YOUR IDEAS WE ABSOLUTELY WILL. THANK YOU FOR ALL THOSE GREAT IDEAS. I HAD A NUMBER OF AHA MOMENTS MYSELF. SO THIS IS AN UPDATE ON A PROGRAM THAT ORIGINATED IN THE CAN REVIEW BOARD, AND HAS NOW BECOME QUITE AN EXTRAORDINARY PROGRAM THAT WE'RE SO EXCITED ABOUT EVEN THOUGH WE'RE KIND OF IN MID-STAGE HERE THAT WE WANTED TO GIVE YOU A SENSE OF BOTH THE SCIENCE AND SOCIOLOGY HERE. SO THIS IS GOING TO BE A TWO-PART PRESENTATION, THE FIRST IS FROM CHRISTINE COLVIS AND NOEL SAFFOLD, THE DYNAMIC DUO AT NCATS. CHRISTINE IS NEUROPHARMACOLOGIST BY TRAINING AND IS THE MOTHER OF THE NTU PROGRAM, IF YOU REMEMBER THAT PROGRAM. THE NEW THERAPEUTIC USES PROGRAM. ANOTHER REALLY INNOVATIVE PROGRAM, NOEL SOUTHHOLD HAS BEEN ON THE INFORMATIC SIDE TWO YEARS AND THEY ARE MANAGING THE PROGRAM TOGETHER. WE'LL HEAR FROM STANLEY AHALT, ONE OF THE P.I.s IN THE PROGRAM, DIRECTOR OF THE RENAISSANCE COMPUTING INSTITUTE AT THE UNIVERSITY OF NORTH CAROLINA CHAPEL HILL. SO CHRISTINE, TAKE IT AWAY. >> ALL RIGHT. THANK YOU, CHRIS. SO DR. AUSTIN GIVE A VERY NICE OVERVIEW OF THIS PROGRAM AT THE LAST COUNCIL, BUT FOR THOSE WHO WEREN'T THERE OR WHO DIDN'T HAVE AN OPPORTUNITY TO SEE THAT, I'M GOING TO GIVE YOU A QUICK OVERVIEW AND THEN WE HAVE A REALLY EXCITING FINISH AT THE END OF THIS. SO THE GOAL OF THE TRANSLATOR PROGRAM IS REALLY TO REVEAL NEW CONNECTIONS AMONG EXISTING DATA. AND THE INTENT AND HOPE IS THAT THIS IS GOING TO LEAD TO NEW INSIGHTS TO NEW RESEARCH OPPORTUNITIES, NEW INTERVENTION OPPORTUNITIES, POTENTIALLY NEW PATIENT POPULATIONS AS WE GAIN BETTER UNDERSTANDING OF BIOLOGY, AND, YOU KNOW, THE END GOAL FOR US OF COURSE IS ALWAYS MORE SUCCESS IN CLINICAL TRIALS. SO WHEN I SAY EXISTING DATA TYPES, NOT JUST PRE-CLINICAL DATA BUT THE IMPORTANT THING IS WE WANT TO TAKE THINGS THAT ARE AT THE DATA AT THE MOLECULAR LEVEL AND BE ABLE TO CONNECT THEM TO THINGS AT THE HUMAN LEVEL, THINGS IN CLINICAL TRIALS AND IN HEALTH RECORDS. SO IN CHRIS' PRESENTATION LAST TIME DURING THE DISCUSSION THERE WAS A QUESTION RAISED ABOUT USE CASES. FROM THE VERY BEGINNING OF THIS PROGRAM FOR OUR -- IN OUR MINDS WHAT WE'RE TRYING TO DEVELOP IS A TOOL THAT'S GOING TO BE HELPFUL TO TRANSLATIONAL RESEARCHERS AND HELP THEM ANSWER QUESTIONS, IT'S GOING TO HELP THEM COLLECT INFORMATION TO ANSWER QUESTIONS. AND SO RAG GUHA, MEMBER OF THE NCATS TEAM ON THIS, CAME UP WITH THIS VERY NICE SCHEMATIC THAT SORT OF LAYS OUT A SPECTRUM OF TIMES OF QUESTIONS THAT ONE MIGHT ASK AND SEEK RESPONSE FOR. ON THE LEFT-HAND SIDE WE HAVE RELATIVELY SIMPLE QUESTIONS, WHAT, WHICH, WHERE TYPES OF QUESTIONS. THESE TYPES OF QUESTIONS WE MIGHT BE ABLE TO LOOK AT THE ANSWER, SINGLE DATABASE OR MIGHT REQUIRE US TO LOOK AT DIFFERENT DATABASES BUT WE CAN PROBABLY DO THIS MANUALLY. QUESTIONS MORE DIFFICULT TO ANSWER ARE WHY, HOW IS THIS OCCURRING, WHAT IF WE MANIPULATED THIS MOLECULE IN THIS CELL? WHAT MIGHT ACTUALLY HAPPEN? YOU CAN IMAGINE THESE QUESTIONS ON RIGHT-HAND SIDE ARE MUCH MORE DIFFICULT TO ANSWER. SO WHAT WE WANT TO DO WITH TRANSLATOR IS TO BE ABLE TO PROVIDE A DOSSIER OF INFORMATION THAT WOULD HELP AN INVESTIGATOR SORT OF FOCUS THEIR SEARCH AND WHERE THEY SORT OF GIVE THEM THE HIGHLIGHTS OF WHERE THEY SHOULD BE OF SHOULD BE LOOKING IN ORDER TO ANSWER THOSE QUESTIONS. AND WE KNOW ANSWERING THOSE QUESTIONS ON THE RIGHT-HAND SIDE OF THE SPECTRUM WILL BE EXTREMELY CHALLENGING SO WE DIDN'T WANT TO JUST JUMP IN AND START BUILDING SOMETHING. WE'RE TAKING A COUPLE YEARS TO DO FEASIBILITY ASSESSMENT. WE WANT TO UNDERSTAND WHAT'S GOING TO BE TECHNICALLY AND SCIENTIFICALLY POSSIBLE, WHAT IS IT GOING TO COST. SO WE'RE STARTING OUT WITH IDENTIFYING HIGH VALUE DATA SOURCES, DEVELOPING A PLAN FOR INTEGRATING ACROSS THE VARIOUS DIFFERENT DATA TYPES AND I'LL SHOW YOU A MODEL WE HAVE FOR THAT. WE'VE BEEN FOCUSED ON DEVELOPING QUERIES FROM THE VERY BEGINNING INCLUDING AT THE POINT THAT WE WERE -- WHEN WE SOLICITED APPLICATIONS WE ASKED FOR QUERIES FROM THE APPLICANTS, AND THEN WE WANT TO RUN DEMONSTRATION PROJECTS TO REALLY SEE WHERE WE ARE ABLE TO ADDRESS QUESTIONS AND WHERE WE'RE STILL GETTING HUNG UP. THE HORIZON IS MORE OF A 10-YEAR HORIZON OR GREATER. WE'RE NOT LOOKING AT FEASIBLE IN 2 YEARS. WE'RE LOOKING AT HOW ARE WE GOING TO WANT TO MINE THE DATA TEN YEARS FROM NOW? WHAT WE WANT TO DO AT THE END IS DEFINE REQUIREMENTS FOR BUILDING A TRANSLATOR. ABOUT A YEAR AGO WE MADE FIVE AWARDS, AND WITH THOSE FIVE AWARDS WE CAPTURED 11 INSTITUTES, NOW WE'RE UP TO 12, OVER 30 INVESTIGATORS PLUS STAFF ALL WORKING ON THIS, ON THIS PROBLEM. THIS IS AN INTENSELY COLLABORATIVE PROGRAM, NOT ONLY AMONG THESE INSTITUTIONS AND ALL THE INVESTIGATORS WHO ARE INVOLVED IN THIS BUT ALSO WITH THE NCATS STAFF, SO NCATS STAFF ARE INVOLVED IN BIWEEKLY TO WEEKLY MEETINGS ON PHONE CALLS WITH THESE TEAMS, AND THEN EVERY 3 TO 5 MONTHS WE ACTUALLY BRING EVERYBODY TOGETHER PHYSICALLY FOR FACE-TO-FACE MEETINGS. WE'VE DONE FACE-TO-FACE MEETINGS THREE TIMES EVEN THOUGH WE HAVEN'T BEEN STANDING A YEAR YET. IN THE JANUARY MEETING, WE AGREED AS A GROUP WE WOULD PURSUE A BLACKBOARD ARCHITECTURE. A BLACKBOARD ARCHITECTURE, THIS IS THAT DESIGN THAT iPSC STORY I REFERRED TO, IT CONSISTS OF THREE COMPONENTS. YOU HAVE A BLACKBOARD, WHICH IS BASICALLY A WORKSPACE, WHERE A QUESTION WOULD BE POSTED, AND THEN YOU HAVE KNOWLEDGE SOURCES WHO ARE NOW LOOKING AT THE BLACKBOARD AND ARE GOING TO RESPOND TO THAT QUESTION. SO YOU MIGHT HAVE ONE OR TWO KNOWLEDGE SOURCES THAT ARE ABLE TO IMMEDIATELY RESPOND TO WHATEVER IT IS THAT'S POSTED AS A QUESTION ON THE BLACKBOARD, AND THEN YOU MIGHT HAVE OTHER KNOWLEDGE SOURCES THAT COULDN'T REALLY RESPOND TO THE ORIGINAL QUESTION BUT NOW THAT THEY SEE THE INFORMATION THAT ANOTHER KNOWLEDGE SOURCE HAS CONTRIBUTED THEY ARE ABLE TO ADD INFORMATION TO THAT. THIS IS A SYSTEM THAT'S VERY SUITABLE FOR OPEN-ENDED PROBLEMS WITH NO OBVIOUS LINE OF ATTACK, PROBLEMS THAT REQUIRE DYNAMIC DECISION MAKING AND THAT ARE GOING TO SPAN MANY DOMAINS AND LEVELS OF ABSTRACTION. IT INHERENTLY LENDS ITSELF TO MICROSYSTEM ARCHITECTURE. KNOWLEDGE SYSTEMS DO NOT HAVE TO HAVE KNOWLEDGE OF EACH OTHER, THEY SIMPLY WORK THROUGH THE BLACKBOARD, THE WAY THEY COLLABORATE TOGETHER. WHEN I SHOWED YOU THE INSTITUTIONS, FOR RIGHT NOW THOSE ARE OUR KNOWLEDGE SOURCES. THEY ARE SERVING AS KNOWLEDGE SOURCE AND WE HAVE A BLACKBOARD THAT WE'RE WORKING ON TO SORT OF TEST THIS ARCHITECTURE AND SEE HOW WELL THIS WORKS TO ANSWER COMPLEX QUESTIONS. THE PIECE WE'RE STILL MISSING IS THIS REASONING TOOL. THE REASONING TOOL CAN BE THOUGHT OF AS THE BRAIN OF THE BLACKBOARD ARCHITECTURE, IT'S GOING TO BE RESPONSIBLE FOR INVOKING KNOWLEDGE SOURCES WHEN NECESSARY AND ALSO FOR MAKING A CALL FOR WHEN A QUESTION HAS BEEN SORT OF ADEQUATELY KIND OF PLATEAUED IN TERMS OF RESPONSES AND THE ANSWERS THAT IT HAS PROVIDED. SO KNOWING THAT THIS IS SOMETHING THAT REALLY IS VERY CRITICAL, WE NEED TO TEST THIS TO UNDERSTAND WHETHER OR NOT THIS IS IN FACT AN ARCHITECTURE THAT'S GOING TO WORK. AS OF ABOUT AN HOUR AND TEN MINUTES AGO, WE HAVE POSTED A FUNDING OPPORTUNITY TO BUILD A REASONING TOOL. IF YOU GO TO THE URL YOU WILL SEE A NOTICE ANNOUNCING THIS OPPORTUNITY. AS WE DID FOR THE ORIGINAL APPLICATIONS, WE ARE USING AN OTHER TRANSACTION AUTHORITY UNDER CURES ACCELERATION NETWORKS, THESE ARE NOT GRANTS, CONTRACTS OR COOPERATIVE AGREEMENTS. YOU DON'T HAVE TO BE AFFILIATED WITH AN ORGANIZATION OR INSTITUTION, IF YOU'RE A U.S. CITIZEN YOU CAN APPLY. IF YOU HAVE A SON OR DAUGHTER WHO IS A WHIZ BANG SCIENTIST OR COMPUTER MAJOR THAT NEEDS TO PAY FOR THEIR EDUCATION, GIVE US A SHOT. OF COURSE, IT IS ALSO OPEN TO U.S. AND FOREIGN ORGANIZATIONS AND INSTITUTIONS AS WELL. WE SET ASIDE $3 MILLION, HOPING TO TEST OUT THREE PROTOTYPES FOR THE REASONING TOOL. IT'S A VERY SHORT PROJECT PERIOD BECAUSE, AGAIN, WE'RE JUST DOING THE FEASIBILITY ASSESSMENT FOR THIS. IT'S A 10-MONTH PROJECT PERIOD. FOR THAT REASON WE'RE USING A VERY UNUSUAL THREE-STEP APPLICATION PROCESS. THIS IS WHERE FOR ME IT GETS EXCITING. STEP 1 IS MOST EXCITING. WE HAVE A NOTICE ON THE WEBSITE THAT I HAVE THE LINK FOR. IT'S A NOTICE WHICH MEANS IT'S NOT THE ACTUAL FUNDING OPPORTUNITY ANNOUNCEMENT. IN ORDER TO ACCESS THE FUNDING OPPORTUNITY ANNOUNCEMENT, YOU NEED TO COMPLETE A SERIES OF COMPUTATIONAL TASKS. WE REFER TO THIS AS THE CHALLENGE. IT'S A SERIES OF COMPUTATIONAL TASKS SO AS YOU COMPLETE EACH TASKS YOU GAIN ACCESS TO MORE OF THE FUNDING OPPORTUNITY ANNOUNCEMENT AND THE INSTRUCTIONS FOR SUBMITTING THE REQUIRED CONCEPT LETTER. DON'T FEEL LIKE YOU HAVE TO GO IT ALONE. THE COMPUTATIONAL TASK CAN BE DONE AS A TEAM. AS LONG AS YOU'RE USING -- AS LONG AS YOUR TEAM IS USING THE SAME LOG-IN FOR THIS ONE TEAM MEMBER MIGHT SOLVE THE FIRST TASK, AS SOON AS THEY DO THE GATE OPENS AND THE ENTIRE TEAM WILL PROGRESS TO THE NEXT STEP AND SOMEBODY ELSE MIGHT GO IN AND SOLVE THE NEXT ONE. AS YOU DO THIS YOU'RE SEEING MORE FUNDING OPPORTUNITY ANNOUNCEMENT AND INSTRUCTIONS. STEP 2 IS REQUIRED, SUBMIT A CONCEPT LETTER. NOTICE THE DATE. TWO WEEKS FROM TOMORROW. WE'RE LOOKING FOR PEOPLE WHO HAVE BANDWIDTH WHO CAN DO THIS IN TWO WEEKS, SOLVE THE CHALLENGE AND YOU'RE GOING TO SEND US THE LETTER. THERE ARE SPECIFIC INSTRUCTIONS FOR THE LETTER. LETTERS WILL GO THROUGH EVALUATION, AND THROUGH EVALUATION PROCESS, AND SO THE SUCCESSFUL TEAMS ARE GOING TO RECEIVE WRITTEN NOTIFICATION FROM US WITH INSTRUCTIONS FOR HOW TO SUBMIT A FULL PROPOSAL AND AT THAT POINT YOU'D BE TELLING US WHAT YOUR BUDGET IS GOING TO BE AND GIVING US MORE DETAILS ABOUT THE PROTOTYPE. I WANT TO EXPLAIN MORE ABOUT THAT CHALLENGE BECAUSE THAT'S WHERE WE'RE SORT OF BREAKING FROM TRADITION AT THE NIH. I TOLD YOU THAT THIS IS A 10-MONTH PROJECT PERIOD. WE CAN'T AFFORD A LONG START-UP RAMP-UP PERIOD FOR ANYONE THAT WE MAKE THIS AWARD TO. WE NEED YOU TO HIT THE GROUND RUNNING. SO THE CHALLENGE IS DESIGNED TO ENSURE APPLICANTS HAVE THE REQUISITE SKILLS TO DEVELOP A REASONING TOOL. WE'RE SAYING DON'T JUST TELL US YOU HAVE THE SKILLS. SHOW US. SHOW US BY MAKING IT THROUGH THIS CHALLENGE. THE TASKS THEMSELVES ARE ACTUALLY DESIGNED TO GIVE YOU BACKGROUND AND INSIGHT INTO BUILDING A REASONING TOOL FOR THIS PROGRAM. YOU WILL ACTUALLY BE WORKING WITH DATA AND RESOURCES FROM THE PROGRAM IN THE PROCESS OF GOING THROUGH THE CHALLENGE AND COMPLETING THOSE TASKS. AND AS I MENTIONED, UPON SUCCESSFUL COMPLETION OF EACH OF THE TASKS, ADDITIONAL SECTIONS OF THE FUNDING OPPORTUNITY WILL BE REVEALED. OF COURSE IN THE INTEREST OF COMPLETE TRANSPARENCY, AFTER THE DATE CLOSES FOR THAT CONCEPT LETTER COMMISSION WE WILL MAKE THIS FUNDING OPPORTUNITY ANNOUNCEMENT AVAILABLE TO EVERYBODY SO YOU CAN SEE WHAT THAT ANNOUNCEMENT WAS ALL ABOUT AND THAT WILL BE ON OUR WEBSITE AFTER SEPTEMBER 22. SO AGAIN THE SITE TO GO TO IS HERE, VERY HOT OFF THE PROS PRESSES. BEFORE I INTRODUCE DR. AHALT, WE'LL HAVE AN OPEN MEETING ON OCTOBER 25, THIS IS GOING TO BE HOSTED ACTUALLY AT THE RENAISSANCE COMPUTING INSTITUTE, RENCI WHERE DR. AHALT IS FROM, GIVING YOU AN OPPORTUNITY TO HEAR FROM EACH OF THE TEAMS TO GET UPDATES FROM THEM TO BRAINSTORM WITH US, BECAUSE THIS IS AN OPEN MEETING AND WE HAVE LIMITED SEATING WE ASK THAT YOU DO GO TO THE WEBSITE TO GET THE LINK TO REGISTER FOR THE MEETING WE'LL HAVE WEBEX AVAILABLE. THERE'S AN OPPORTUNITY TO REGISTER TO ATTEND IN PERSON OR WHETHER YOU'LL BE PARTICIPATING BY WEBEX. WITH THAT I I WANT TO INTRODUCE DR. AHALT, DIRECTOR OF RENCI -- THAT WAS THE RENAISSANCE COMPUTING INSTITUTE -- AT THE UNIVERSITY OF NORTH CAROLINA CHAPEL HILL, HE'S PROFESSOR IN THE UNIVERSITY OF NORTH CAROLINA COMPUTER SCIENCE DEPARTMENT, AND ASSOCIATE DIRECTOR AT THE BIOMEDICAL INFORMATICS SERVICES OF THE NORTH CAROLINA TRANSLATIONAL AND CLINICAL SCIENCES INSTITUTE. DR. AHALT IS ONE OF THOSE INVESTIGATORS THAT WE SUPPORTED ABOUT A YEAR AGO, THIS IS SUCH A FAST-PACED PROGRAM THAT I THINK HE HAS QUITE A BIT TO SHOW YOU AND TALK TO YOU ABOUT AND ONE OF THE REASONS THAT WE WERE REALLY EXCITED TO HAVE THEIR TEAM IN IS BECAUSE HE'S GOING TO TELL YOU ABOUT SOME VERY UNIQUE DATA TYPES THAT I THINK ARE OFTENTIMES NEGLECTED WHEN WE TALK ABOUT BIOMEDICAL RESEARCH AND HIS TEAM IS REALLY PARTICULARLY I THINK REALLY EMBODIES COLLABORATION SO WE'RE REALLY VERY HAPPY TO HAVE HIM AND HIS TEAM AS PART OF THE TRANSLATOR PROGRAM. SO STAN, WITH THAT. >> IF YOU LOOK AT THE SCHEDULE WE WERE SUPPOSED TO START THIS AT 10:45. AND IT'S 11:45. AND BEING A DUTIFUL COMPUTER SCIENTIST, ENGINEER, I'VE GOT A LOT OF SLIDES. [LAUGHTER] I WILL TRY TO GO QUICKLY. I HAVE 50 SLIDES. I WANT TO ALLOW YOU TO EAT BECAUSE I KNOW WHEN YOU'RE HUNGRY YOU WANT TO EAT. >> I THINK FOR THE COUNCIL, I SAY KNOWLEDGE IS MUCH MORE IMPORTANT THAN FOOD. [LAUGHTER] KNOWLEDGE IS OUR FOOD, WHICH SUSTAINS US. SO PROCEED. >> SO I DO WANT TO SAY THANK YOU ALL FOR ALLOWING ME TO DO THIS. THIS IS AN OPPORTUNITY FOR US TO EXPLAIN A PHENOMENA THAT IS JUST AMAZING. AND I'M THE P.I. OF THE GREEN TRANSLATOR TEAM. THAT'S THE REASON I WORE THIS TIE. COLORS HAVE FACTORS IN. THIS IS A SOCIOTECHNICAL EXPERIMENT, I'LL TAKE A FEW MINUTES TO SAY THIS IS THE MOST EXCITING PROJECT I'VE EVER HAD IN MY CAREER, I'M NOT TRYING TO PANDER TO THE AUDIENCE. I SPENT 15 YEARS DOING RESEARCH FOR DEPARTMENT MUCH DEFENSE, PRINCIPAL INVESTIGATOR FOR SIGNAL AND IMAGE PROCESSING. I'M INTERESTED IN SENSOR FUSION, TAKING DATA FROM DIFFERENT SOURCES. THIS IS A PROBLEM LIKE THIS. WE TALKED ABOUT DEMOCRATIZATION OF CHEMISTRY EARLIER, INTERESTING INSIGHT. LAST NIGHT I WAS THINKING WHAT ARE WE DOING? DEMOCRATIZING OR LIBERATING BIOMEDICAL AND HEALTH SCIENCE DATA. I ACTUALLY THINK WE'RE GOING TO SUCCEED. WE'RE MAKING SIGNIFICANT PROGRESS. IT'S A JOY TO BE PART OF THE TECHNICAL AND SOCIAL PROCESS. I SHOULD GO BACK. I WANT TO SAY THAT EVEN THESE SLIDES WERE A TEAM EFFORT, EVERY TEAM SUBMITTED PIECES OF SLIDES AND IT RATED WITH ME. THAT'S THE NUMBER OF TEAMS INVOLVED BUT THEY ARE ACTING LIKE A SINGLE TEAM TOGETHER. THAT IS AN AMAZING OUTCOME AFTER A SHORT PERIOD OF TIME. THAT LITTLE SYMBOL IS ECHOED IN THE PAGE NUMBERS AT THE BOTTOM TO REPRESENT UNIFICATION OF THIS PROCESS. I WAS SURPRISED IN THE FIRST MEETING WHEN DR. AUSTIN SAID THAT WE DON'T KNOW HOW MANY DISEASES THERE ARE. I DON'T KNOW WHY I DIDN'T REALIZE THIS ALREADY. I FEEL SILLY FOR NOT KNOWING THIS. AFTER THE MEETING I READ PAPERS AND REALIZED WE DON'T KNOW A LOT ABOUT HOW MANY REAL DISEASES THERE ARE. SOMEBODY MENTIONED TODAY THERE'S ABOUT 7,000. I'VE HEARD THAT NUMBER CONSISTENTLY, RARE DISEASES WHICH INDICATES THERE'S A LOT OF DISEASES OUT THERE. AFTER RESEARCH I DISCOVERED MULTIPLE DEFINITION OF WHAT A DISEASE IS, THERE ARE CHANGING DEFINITIONS OVER THE YEARS, INCONSISTENT, DEPENDING UPON WHERE YOU LOOK AND HARD TO DISTINGUISH IN SOME CASES. THAT'S EXACTLY WHAT I WANT TO TALK ABOUT IS TRYING TO DISTINGUISH DISEASES BETTER AND DISEASE CHARACTERIZATION DOES PRESENT NEW OPPORTUNITIES FOR MARKETS AND DRUGS AND THINGS LIKE THAT. ONE OF THE GOALS OF THIS EFFORT PARTICULARLY THE TEAM THAT I'M ON IS TO LOOK AT A NEW APPROACH AND FRAMEWORK FOR UNDERSTANDING DISEASES. I WANT TO GIVE YOU FIRST A ROAD MAP TO THE ENTIRE TALK. SO IT'S A PRETTY COMPLEX PRESENTATION BECAUSE WE COUNTED UP AND ACTUALLY HAVE ABOUT 100 PEOPLE, NOT ALL ARE FUNDED. THEY ARE INVOLVED BECAUSE THEY KNOW THAT THEY ARE GOING TO LEARN SOMETHING AND TAKE IT BACK TO THEIR OTHER PROJECTS. SO TO SOME DEGREE YOU'RE GETTING AMPLIFICATION EFFECT THAT IS ADMIRABLE. I'M GOING TO TALK ABOUT DEFINING DISEASES, MOVING BEYOND PHENOTYPES TOWARD ENDOTYPES THROUGH DEGENERATION THROUGH INTEGRATED KNOWLEDGE SOURCES, EMBRACING CHALLENGE AROUND TECHNOLOGIES, AROUND THE TEAM SCIENCES, IN ORDER TO IMPROVE TREATMENT RESPONSE AND FACILITATE DRUG DISCOVERY AND THEN I WANT TO TALK ABOUT THE KEY DRIVERS TO SUCCESS IN THIS PROGRAM. PHENOIS IS A GREEK WORD MEANING APPEARING OR SEEMING, ENDOMEANS IN THE HOUSE. WHAT YOU CAN SEE AND OBSERVE FROM THE OUTSIDE AND GET TO SEE IF YOU LOOK UNDER THE COVERS, INSIDE YOURSELF, OKAY? ROUGHLY SPEAKING THAT'S WHERE WE ARE CURRENTLY WITH TRYING TO UNDERSTAND. WE WENT THROUGH A PROCESS, ITERATIVE PROCESS WITH FOLKS ON DIFFERENT TEAMS AND CAME UP WITH THESE DEFINITIONS. HERE WE'RE LOOKING AT PEDIATRIC ASTHMA, IN A MINUTE I'LL SHOW YOU THE QUERY. WE PICKED PEDIATRIC ASTHMA BECAUSE IT'S SO CHALLENGING FOR IT TURNS OUT DAVE PEEDEN. OF THE ASTHMA SOCIETY, IT'S DIFFICULT TO TREAT AND WOULD LIKE TO DIFFERENTIATE PEDIATRIC PATIENTS. WE DEFINED CLINICALLY OBSERVABLE SIGNS AND SYMPTOMS SUCH AS TRAITS LISTED HERE AND THOSE GUIDE DIAGNOSIS, TREATMENT SELECTION AND PROGNOSIS. AND SIMILARLY WE DEFINE THE ASTHMA ENDOTYPE AS THE THINGS THAT LINK THE ETIOLOGY OF THE DISEASE AND ITS UNDERLYING PATHOPHYSIOLOGY BY INTEGRATED CLINICALLY OBSERVABLE SIGNS AND SYMPTOMS INCLUDING THINGS LIKE BIOMARKERS, BIOLOGICAL PATHWAYS, GENETIC BACKGROUND, SOCIOENVIRONMENTAL EXPOSURE. WE'RE INTERESTED IN LOOKING AT LOTS OF FACTORS THAT CAN HAVE AN IMPACT ON ANY GIVEN PATIENT. SO HERE IS A MORE SCHEMATICKIZED WADE OF LOOKING AT THIS. ON THE LEFT YOU SEE A PATIENT THAT IS EXHIBITING CERTAIN TYPES OF PHENOTYPICAL TRAITS, ON THE RIGHT YOU'D LIKE TO BE ABLE TO SAY WHICH IS THE CATEGORY OF THIS PARTICULAR PATIENT, SO THAT I CAN FIGURE OUT HOW TO TREAT THAT PATIENT AND LATER I'M GOING TO COME BACK AND MENTION TO YOU ALL WE WANT TO BE ABLE TO DO OTHER THINGS WITH THIS LINKAGE TOO, IT'S NOTE JUST FOR TREATMENT OR CLINICAL RESEARCHERS, IT'S ALSO FOR THE RESEARCH SCIENTIST. IN THE MIDDLE IS THINGS WE WANT TO FIGURE OUT HOW TO COUPLE TOGETHER THESE TRANSLATOR KNOWLEDGE SOURCES, SO THINGS LIKE ENVIRONMENTAL EXPOSURE, SOCIOENVIRONMENTL EXPOSURES, WHETHER YOU LIVE IN A HIGH CRIME NEIGHBORHOOD OR LIVE CLOSE TO A ROADWAY, MEDICATION EXPOSURES, TREATMENT RESPONSE, BIOLOGICAL PATHWAYS, PROTEIN AND GENE TARGETS. SO WE WANT TO PUT ALL OF THE DATA AT THE DISPOSAL OF RESEARCHERS AND CLINICIANS. WE WANT TO FIGURE OUT A WAY WE CAN HAVE PEOPLE BE ABLE TO DISCOVER NEW POSSIBILITIES IN THE DATA SOURCES AND I'M GOING TO COME BACK TO WHY THAT'S SO IMPORTANT AND WHY IT'S HAPPENING NOW BECAUSE I THINK THAT'S AN INTERESTING STORY IN AND OF ITSELF. SO CHRISTINE MENTIONED THESE QUERIES. INTERESTINGLY ENOUGH, EVEN THE DEFINITION OF QUERY HAD TO BE REFINED BECAUSE DIFFERENT TEAMS HAD DIFFERENT IDEAS WHAT A QUERY MEANT AND WE'RE CONVERGING, I DON'T KNOW THAT WE'RE CONVERGED, BUT THE GREEN TEAM ORDERED ITS -- EACH TEAM HAS QUERIES, AND IT HELPS US UNDERSTAND BECAUSE QUERIES MAKE CONCRETE WHAT ARE KIND OF SOMETIMES NOT NECESSARILY WELL UNDERSTOOD VOCABULARIES, OKAY? SO WE HAVE SIMPLE QUERIES LIKE THE ONE AT THE TOP, IS EXPOSURE TO AIRPORT MATTER AND OZONE EXPOSURE WITH AN ASTHMA-LIKE PHENOTYPE. WE KNOW THE ANSWER. WE BETTER BE ABLE TO USE KNOWLEDGE SOURCES TO GET AN ANSWER THAT SAYS YES. THAT'S ONE OF THE FIRST THINGS WE'RE DOING MAKING SURE WE CAN TEST THE DATA SOURCES AND KNOWLEDGE SOURCES THAT WE'RE HOOKING UP AND GET ANSWERS TO KNOWN QUESTIONS. QUESTIONS THAT WE ALREADY KNOW THE ANSWER TO TO MAKE SURE DATA IS HOOKED UP CORRECTLY AND BE ABLE TO POSE SOPHISTICATED QUERIES, DOES EXPOSURE TO PM 2.5 OR OZONE IN THE PERINATAL PERIOD INDUCE CHRONIC LUNG DISEASE LATER IN CHILDHOOD. THERE'S SOME EVIDENCE IF YOU ARE EXPOSED TO ACUTE CONCENTRATIONS IT TURNS OUT TO HARM YOU LATER, DOWNSTREAM. AND WHY IS THAT? WHY ARE WE OBSERVING THAT? TAKING A STEP BACK FOR A SECOND, KNOWLEDGE SOURCES THAT WE'RE LOOKING AT WE HAVE PATIENT DATA FROM ACROSS NORTH CAROLINA, THIS IS NORTH CAROLINA CENTRIC WHERE WE CAN GET OUR PATIENT DATA. WE HAVE ENVIRONMENTAL DATA, THIS IS A PICTURE OF THE CHAPEL HILL AREA, MY OFFICE IS NEAR ONE OF THOSE BIG DARK BLOTS WHICH TURNS OUT TO BE A HIGH POLLUTION AREA DURING CERTAIN -- WHEN THERE'S A LOT OF TRAFFIC ON ON THE INTERSTATES. SOCIOECONOMIC AND CHEMICAL AND BIOLOGIC. FOR EXPOSURE DATA WE'RE USING THE EPA NATIONAL AIR QUALITY SYSTEM POLLUTION DATA AND U.S. NATIONAL ALLERGEN EXPOSURE DATA AND U.S. DEPARTMENT OF TRANSPORTATION ROAD SYSTEM DATA. AND THAT IS BEING DONE LARGELY THROUGH THE INSTITUTE OR ENVIRONMENT AT UNC, THEY HAVE BUILT A SERIES OF SOPHISTICATED MODELS TAKING INTO ACCOUNT WIND SPEEDS, DIRECTION, HUMIDITY. YOU CAN GET FAIRLY ACCURATE IDEAS HOW MUCH EXPOSURE A PARTICULAR PATIENT HAS HAD DEPENDING UPON GEO LOCATION. THE PATIENT DATA IS FROM THE CAROLINA DATA WAREHOUSE, I HAVE MORE TO SAY ON OY ON THIS IN A MINUTE, WE HAVE A MILLION ACTIVE PATIENTS, SINCE 2004, PEOPLE SEEN I THINK TWICE IN THE LAST TWO YEARS OR MORE THAN TWO TIMES IN THE LAST TWO YEARS. AND IT IS BASICALLY LINKED INTO THE OTHER DATA BY WAY OF GEO CODES. I'M GOING TO COME BACK TO THE ISSUE OF HOW WE'RE GETTING AROUND SOME INTERESTING HIPAA REQUIREMENTS AND IRB ISSUES AROUND PATIENT DATA AND WHEN I SAY GETTING AROUND I MEAN ADHERING TO ALL OF THE RULES AND DOING IT IN A WAY THAT'S SAFE. PLEASE DON'T MISCONSTRUE MY WORDS. SOCIOENVIRONMENTAL DATA ON THE LEFT THERE U.S. CENSUS BUREAU AMERICAN COMMUNITY SURVEY AND FROM FBI UNIFORM CRIME REPORTING SYSTEM AND WE'RE CALCULATING A NUMBER THAT WE THINK IS A REASONABLE PROXY FOR STRESS ORIGINATING WHERE YOU LIVE AND PERHAPS WHERE YOU GO TO SCHOOL. CHEMICAL AND BIOLOGICAL WE HAVE DIFFERENT SOURCES, A LOT IS BEING DONE FROM THE CHEMO TEXT AND MAN TO MOLECULES TO MAN PROJECT LED BY MY CO-P.I. ALEX, SO WE HAVE A COMPUTATIONAL CHEMIST ON THE STAFF TRYING TO HELP UNDERSTAND DATA. THERE ARE OTHER SOURCES THAT WE'RE LOOKING AT AS WELL IN THE CHEMICAL AND BIOLOGICAL SPACE INCLUDING FEARS, ADVERSE RESPONSE REPORTING SYSTEM AND CIDER DATABASE AND clinicaltrials.gov. SO JUST I DON'T WANT TO SPEND A LOT OF TIME. WE'VE DONE A PRELIMINARY CURSORY REVIEW OF THE DATA, WE WENT BACK TO 2010 AND 2011 EVENTS WE ALREADY CALCULATED. ON THE LEFT IS POLLEN COUNTS, YOU SEE IT SPIKING IN I BELIEVE APRIL PRIMARILY, DOWN AT THE DECEMBER. SURE ENOUGH ADMISSION INTO EMERGENCY ROOMS PEAK RELATIVE TO PRIOR MONTHS AT ABOUT THE SAME CORRELATION. WE'RE ABLE TO SEE THE RIGHT CORRELATIONS IN THE DATA. I SHOULD SAY THAT IN THIS CASE WE'RE LOOKING AT A SPECIFIC SET OF PATIENT DATA. I WANT TO TELL YOU MORE ABOUT THAT. SO BEFORE I GET INTO THE PATIENT DATA AND WHAT IT REALLY MEANS LET ME GIVE YOU A CONCEPTUAL VIEW OF MOVING BEYOND THE PHENOTYPE. ON THE LEFT IS THE IDEA OF THIS PHENOTYPE SPACE. IT'S AN END DIMENSIONAL VECTOR THAT CAPTURES AGE, RACE, SEX, PRIMARY RESIDENCE, PARENTAL SMOKING STATUS, THINGS LIKE THAT. IN THE MIDDLE IS THIS ENDOTYPE SPACE, OKAY, WHICH IS EXPOSURE HISTORY, OZONE EXPOSURE HISTORY, ROADWAY, SOCIOENVIRONMENTAL, GENE VARIANTS, BIOLOGICAL PATHWAYS, MEASURABLE THINGS. THE IDEA IS THAT THESE ARE FEATURES THAT HAVE BEEN CAPTURED BY THE TRANSLATOR IN SOME WAYS VERSUS FEATURES THAT ARE CAPTURED IN THE ELECTRONIC MEDICAL RECORD ON THE LEFT, AND WHAT YOU WANT TO DO IS BE ABLE TO CREATE INTERVENTION SPACE, OKAY. THIS IS NOT THE -- SORRY. THIS IS NOT THE ONLY WAY YOU WANT -- NOT THE ONLY THING BUT IT'S ONE OF THEM. THE IDEA IS ARE THERE MEDICATIONS THAT CAN BE APPLIED HIGHLY PROBABLY TO HELP THIS PATIENT OR COGNITIVE BEHAVIORAL THERAPY OR HOME AND LIFESTYLE, MAYBE AN AIR CONDITIONER IS A GOOD USE OF MONEY BECAUSE THIS PATIENT IS JUST EXPOSED CONSTANTLY TO AGGRAVATING IRRITANTS. THEIR IS AN EXAMPLE OF A SPECIFIC CASE. PATIENT IS 12 YEARS OLD, BLACK MALE, LIVES IN DURHAM IN A PARTICULAR AREA, PARENTS BOTH SMOKE, ASTHMA, ET CETERA. YOU CAN SEE THE IDEA OF GOING INTO THESE KNOWLEDGE SOURCES, PULLING OUT SPECIFIC PIECES OF INFORMATION AND THEN ULTIMATELY BEING ABLE TO USE CONTROLLER THAT WE'RE NOW OUT FOR BID, CHALLENGE, COMING UP WITH WAYS TO LOOK AT THE PATIENT AS A SUBGROUP YOU NEED TO TREAT IN A PARTICULARLY THOUGHTFUL WAY OR PARTICULARLY APPROPRIATE WAY. YOU MIGHT GO THROUGH THE SAME TYPE OF PROCESS AND END UP WITH DRUG REPURPOSING OR LOOK AT THE MECHANISTIC DATA, COME UP WITH CHEMICAL NAMES, STRUCTURES, GENES, PROTEIN TARGETS. CAN THE DATA HELP US FORM CONSTRUCTIVE HYPOTHESES ABOUT THIS PARTICULAR PATIENT, OKAY? AND WHAT IN AGGREGATE CAN WE LEARN ABOUT THE GROUPS? WE'RE GOING TO EXPOSE THIS DATA IN A CLEVER WAY SO WE CAN GO AND DO DISCOVERY IN THE DATA ITSELF AND ACROSS THESE DATA SOURCES. SO NEXT I WANT TO SHIFT INTO HOW WE'RE GETTING THIS DONE, THAT WAS THE SETUP FOR US SETTINGS UP THE PROBLEM, OKAY, SETTING UP THE QUERIES. NOW I WANT TO TALK ABOUT THE TRANSLATOR ITSELF AND IN ESSENCE WHAT THIS HAS BOILED DOWN TO IS EMBRACING BOTH THE POWER AND CHALLENGE OF DATA, AND THE POWER AND CHALLENGE OF TECHNOLOGY, AND THE POWER AND CHALLENGE OF TEAM SCIENCE. IT'S PUTTING IT ALL TOGETHER THAT'S SO EXCITING. AND OBVIOUSLY WE HAVE MANY DIFFERENT REASONS TO DO THIS, BUT ONE KEY REASON IS THAT WE WANT TO BE ABLE TO LOOK AT IMPROVED RESPONSIVENESS OR DRUG REPURPOSING. SO DATA IS A FUNDAMENTAL PIECE OF KNOWLEDGE THAT WE'RE ALL COLLECTING MUCH FASTER THAN WE DID IN THE PAST, BUT NOW WE WOULD LIKE TO BE ABLE TO MOVE PAST JUST COLLECTING AND MOVE TO ACTIONABLE DATA. SO ONE OF THE REASONS THAT THIS HAS BEEN SO SUCCESSFUL IS THAT THIS IS THE RIGHT TIME. OKAY? WE'RE COLLECTING HEALTH RECORDS, THEY ARE BEING DIGITALLY CAPTURED IN GREATER VOLUMES, AND WITH THE RICHNESS WE NEVER HAD BEFORE. IF YOU LOOK IN MY HEALTH CARE SYSTEM, USING EPIC DATABASE, CAN YOU FIND AN AMAZING AMOUNT OF INFORMATION. IT'S NOT NECESSARILY EASY TO CONSUME, OKAY? IT'S A COMPLEX DATASET. IT'S SET UP TO FACILITATE PRIMARILY BILLING, OKAY? FOR ALL INTENTS AND PURPOSES. IT HAS SUCH A RICHNESS OF DATA THAT PRESENTS A REAL OPPORTUNITY FOR US. WE'RE COLLECTING BIOACTIVITY DATA, CREATED AND CAPTURED IN A MUCH MORE RAPID FASHION THAN THE PAST. GENOMIC DATA IS NET NECESSARILY A ROUTINE PART OF CLINICAL CARE RIGHT NOW WE ANTICIPATE THAT IN THE FUTURE IT WILL BECOME A ROUTINE PART. SO THE PROBLEM IS THAT THESE THINGS ARE HARD TO HOOK UP. OKAY. THESE DATA SOURCES ARE -- THERE'S MANY CHARACTERISTICS. I'M GOING TO TALK ABOUT POWER AND CHALLENGE OF EACH AND IT TURNED OUT THAT I COULD TAKE THIS CHALLENGE OF DATA SLIDE TEMPLATE AND REPLACE SOME WORDS AND GET THE SAME EFFECT FOR BOTH, FOR DATA AND SCIENCE AND FOR THE TEAMS. SO IT'S AN INTERESTING PARALLEL BETWEEN WHAT WE'RE TRYING TO DO AND HOW WE'VE SET UP - NCATS SET UP THE TEAM SCIENCE. PARALLELS ARE AMAZING. IT'S INCREDIBLE TO LOOK AT HOW MUCH THE TECHNOLOGY MIRRORS THE TEAM SCIENCE AND THE TEAMS, AND IT'S REALLY A GREAT EXAMPLE, I WISH SOMEBODY WAS STUDYING US CLOSELY. WE'RE TRYING TO DO THAT OURSELVES, I'LL TELL YOU ABOUT THAT TOO. DATA SOURCES ARE DIFFICULT TO LOCATE, DIFFICULT TO UNDERSTAND, THEY TYPICALLY USE DIFFERENT VOCABULARIES TO DESCRIBE THE SAME DATA EVEN IF YOU LOOK AT THE SAME PATIENT THAT APPEAR IN THE DUKE'S EPIC DATABASE AND UNC'S EPIC DATABASE, THE PATIENTS CAN LOOK DIFFERENT BECAUSE THE DATA GOES IN DIFFERENCE PLACES. OKAY? IT'S REALLY INTERESTING PHENOMENA THAT YOU HAVE EXACTLY THE SAME TECHNOLOGY IN HEALTH CARE SYSTEMS THAT ARE 8 MILES APART AND PATIENTS ARE SHARED BACK AND FORTH AND THE PATIENT CAN LOOK DIFFERENT. YOU MIGHT NOT NOTICE STARTLING THINGS BEING CAPTURED IN THE ELECTRONIC MEDICAL RECORDS IN A DIFFERENT WAY. WE HAD NO REAL INCENTIVE TO FIGURE OUT HOW TO HARMONIZE DATASETS. LOTS OF DATA IS A PARTICULAR INSTITUTION, AND AS WE HEARD TODAY THEY ARE NOT NECESSARILY EAGER, NOT INCENTED TO GIVE UP THAT DATA AND NOT INCENTED TO TAKE TIME AND ENERGY, RARE DISEASES IS A GREAT EXAMPLE, WHO IS INCENTED TO REALLY MAKE SURE THAT ALL THE PATIENTS THAT YOU'VE SEEN HAVE BEEN EXPOSED AS PATIENTS WHO ARE -- THE ONES YOU'VE SEEN AT LEAST, PATIENTS WITH A RARE DISEASE? YOU MIGHT NOT KNOW IT'S A RARE DISEASE IN SOME CASES, AS A PHYSICIAN, BECAUSE YOU'RE A CLINICIAN MAYBE IN A RURAL AREA AND MAY NOT REALIZE THIS PATIENT THAT I'M SEEING HAS A RARE DISEASE THAT HAS A GENETIC BASIS. THIS IS AN OPPORTUNITY SPACE THAT'S RICH. I'LL COME BACK TO THIS ISSUE OF RARE DISEASES IN NORTH CAROLINA BECAUSE OF SOME VERY SPECIFC THINGS GOING ON THERE. DATA SOURCES CAN BE SENSITIVE, NEED TO HAVE LICENSES THAT CAN HAVE I.P. ISSUES AROUND THEM. MOST IMPORTANTLY WE'VE HEARD TWO OR THREE TIMES TODAY THE NEED FOR REPRODUCIBLE SCIENCE. I THINK THIS IS JUST A STRONG PUSH FROM MANY DIRECTIONS. WE'LL HAVE FIGURE OUT WAYS TO CAPTURE DATA SOURCES AND PROVENANCE, HOW THEY HAVE BEEN HANDLED NOSHED TO MAKE GOOD USE OF THEM -- IN ORDER TO MAKE GOOD USE OF THEM. MANY SOURCES OF DATA WE'RE USING ARE PATIENT DATA AND THE PATIENT DATA IS A PARTICULAR CHALLENGE BECAUSE IT IS A HUGE OPPORTUNITY BECAUSE IT ALLOWS TO US TRAVERSE THE TRANSLATIONAL SPECTRUM TO INFER FROM MOLECULAR DATA IN ANIMAL RESEARCH BACK TO HUMANS, AT LEAST POTENTIALLY SO, OKAY? THEY PROVIDE DATA INTO THE REAL WORLD. WHAT HAPPENS WHEN PATIENTS ARE EXPOSED TO CERTAIN DRUGS? PATIENT DATA ARE INCREASINGLY BEING CAPTURED IN ELECTRONIC MEDICAL RECORDS. OUR WAREHOUSE CONTAINS 5 MILLION PATIENTS FROM 2004 ON WITH GEO CODES, AND IN SOME CASES THE PATIENTS HAVE ACTUALLY BEEN SEEN IN DIFFERENT STATES AND WE NOW KNOW WE HAVE PATIENTS THAT WE'VE SEEN THAT TOUCHED ALL 50 STATES. BUT THE CHALLENGE OF PATIENT DATA IS PARTICULARLY HARD. PATIENT DATA SOURCES CAN BE DIFFICULT TO LOCATE AND UNDERSTAND THEY ALSO TYPICALLY -- NOT TYPICALLY BUT IN MANY CASES USE DIFFERENT TYPES OF VOCABULARIES TO DESCRIBE THE SAME DATA. GEOGRAPHICALLY DISTRIBUTED, VARYING QUALITY AND THE PATIENT DATA SOURCES ARE SENSITIVE. THEY ARE SUBJECT TO HIGH REGULATIONS, SO WE HAVE TO FIGURE OUT HOW WE CAN GET SYSTEMS IN PLACE THAT ALLOW REGULATED DATA TO BE UTILIZED IN CONSTRUCTIVE WAYS. AGAIN, WE NEED TO FIGURE OUT WAYS TO ATTACH PROVENANCE TO THE PATIENT DATA, IN ORDER TO BE ABLE TO DO THE REPRODUCIBLE SCIENCE. MOST PATIENT DATA SOURCES ARE NOT WELL INTEGRATED AND FIRST NEED TO BE EVALUATED TO BE MADE AVAILABLE FOR BROADER USE. IN THIS CASE THE REAL WORLD PATIENT DATA THAT WE HAVE ASSEMBLED AND THAT WE'RE USING NOT JUST FOR OUR TEAM BUT ACROSS TEAMS WE'VE ACTUALLY NOW TRANSFERRED -- WE'RE MAKING PROVISIONS SO OTHER OF THE TEAMS CAN HAVE ACCESS TO OUR DATA. WE ALSO CREATED -- THAT NEEDS AN IRB APPROVAL AND APPROVED WORKSPACE SO THE NECESSARY THINGS IF YOU'RE WORKING ON SENSITIVE DATA HAVE TO BE IN PLACE. THAT DATASET IS A PULL FROM THE ORIGINAL WAREHOUSE, IT'S ABOUT 160,000 PATIENTS WITH ASTHMA-LIKE PHENOTYPES. WE PULLED ICD-9 AND 10 CODES THAT HAVE AN ASSOCIATION WITH RESPIRATORY PROBLEMS. TO CREATE MORE READILY WE CREATED A DATASET HUSH PLUS, ABOUT 16,000 HYPOTHETICAL PATIENTS, IF YOU WILL, FROM THE WAREHOUSE BUT WITH COMPLETELY COMPLIANT WITH THE HIPAA RULES, AND WE'VE ADDED IN SO THAT HUSH COMES FROM THE HIPAA RULE THAT YOU SEE LISTED UP HERE, IT'S A SAFE HARBOR RULE, AND THE PLUS INDICATES WE'VE ADDED ON GEO CODES THAT ARE NOT CORRECT BUT NOW WE HAVE A DATASET THAT'S BEEN CULLED FROM THE 160,000 DOWN TO 16,000 THAT WE CAN PHYSICALLY SHARE WITH PEOPLE AS LONG AS THEY ARE WILLING TO AGREE TO DATA USE AGREEMENT. WE HAVE A COMPLETELY OPEN DATASET THAT SOMEHOW WE HAVE AN OLD SLIDE HERE, WE ACTUALLY REFER TO THIS NOT AS SIN SYNTHETIC BUT TEST PATIENT DATA, DATA GENERATED FROM MATHEMATICAL MODELS SIMILAR TO THE STATISTICS YOU SEE IN THE ELECTRONIC MEDICAL RECORDS, WE PRODUCED THIS DATA TO SHARE THE DATA READILY AMONG US. THE IDEA IS THREE DATASETS ALLOW US TO INCREASINGLY DO THINGS TO MORE SENSITIVE DATA, THE FIRST AT THE BOTTOM HELPS US SIMPLY GET ALL OF THE COMPUTER SCIENCE RUNNING. THE SECOND ONE ALLOWS TO US MAKE SURE WE CAN ASK INTERESTING SCIENCE QUESTIONS ABOUT WHETHER OR NOT THERE'S SOME RELATIONSHIPS, AND FINALLY WHAT WE CAN DO IS TAKE THE TOOLS AND MODELS, MAYBE THE CONTROLLER AND USE IT ON THE ACTUAL DATA ITSELF AT THE VERY TOP. SO HERE IS AN ARCHITECTURE WE'VE NOW STARTED VETTING THROUGH THE APPROPRIATE PEOPLE IN THE TEAM, IN THE INSTITUTIONS. AND WE WANT TO BE ABLE TO MAKE IT SO THAT THEY THROUGH A SINGLE SOURCE OF ACCESS USERS WHO HAVE ROLES, DIFFERENT ROLES POTENTIALLY IN THE SYSTEM CAN HAVE ACCESS TO THE SENSITIVE DATA. THE IDEA IS THAT A USER, BOB AT OHSU IN THIS CASE, WOULD LOG IN THROUGH AN AUTHENTICATION PROCESS, CREDENTIALS WOULD BE PASSED TO THE TRANSLATOR HUB, TRANSLATOR.IO, IN THE CLOUD, AMAZON INSTANCE, PASS THIS INFORMATION BACK TO THE INSTITUTIONS, TO VERIFY THAT THIS PARTICULAR USER HAS THE RIGHT AUTHENTICATION, AND THEN IF INDEED THIS IS THE PERSON THAT THEY REPORT TO BE, BY WAY OF THAT PARTICULAR PASSWORD AND LOGIN, OKAY? NOW CONSIDER THE USER BOB AGAIN WHERE WE CAN ASK NOW THE QUESTION, IS THIS USER ALLOWED TO ACCESS THIS SENSITIVE DATA? OKAY. SO WE'LL HAVE ANOTHER DATABASE IN ADDITION TO AUTHORIZATION DATABASE WHICH ALLOWS US TO ANSWER THE QUESTION, HAS THIS PERSON BEEN GIVEN THE APPROPRIATE LEVEL OF REVIEW, ARE THEY ON THE IRB, AND YOU'LL TALK ABOUT AN IRB THIS AFTERNOON, ARE THEY ON THE IRB AND IF THEY ARE, THEN DO WE GIVE THEM ACCESS? AND INDEED IF THEY ARE, THEY WILL BE ALLOWED TO BE GIVEN ACCESS TO DATA THAT RESIDES BACK AT THE INSTITUTION, I'LL COME BACK TO THIS IN A MINUTE, DATA AT THE INSTITUTION AND IN THIS CASE BOB IS ALLOWED TO, BUT BY THE SAME RIGHT IF BOB HAS NOT BEEN PUT ON THE IRB WE CAN SAY, OKAY, BOCK BOB CAN HAVE ACCESS TO OUR DATA THAT'S NOT SENSITIVE BUT UNFORTUNATELY BOB IS PREVENTED DATA THAT'S SENSITIVE BUT BOB CAN STILL USE DATA FROM HIS OR HER OWN INSTITUTION, COULD BE PATIENT DATA, IN CONJUNCTION ARE OUR DATA BECAUSE NOW WE HAVE GIVEN ACCESS METHODOLOGY SO YOU CAN GET TO SENSITIVE AND NONSENSE NONSENSE ACTIVE DATA. THIS HAS TAKEN 15 MEETINGS AND WE'RE STILL WORKING THROUGH THE SECURITY PEOPLE AT OUR INSTITUTIONS. BUT WE THINK WE MADE SERIOUS PROGRESS. NOW I WANT TO TALK ABOUT POWER AND CHALLENGE OF TECHNOLOGIES, ONE OF THE OTHER INTERESTING THINGS IS THAT THE KNOWLEDGE SOURCES HERE ARE NOT JUST DATA. IT'S ALSO THE PEOPLE THAT ARE INVOLVED. I WANT TO TELL YOU ABOUT THOSE PEOPLE BECAUSE IT'S AMAZING HOW MANY PEOPLE HAVE COME TO THE TABLE. TECHNOLOGY ALLOWS YOU TO SECURELY USE DATA INCLUDING PATIENT DATA TO GENERATE INTERESTING FUNDAMENTAL INSIGHTS, ALLOWS DATA DRIVEN DISCOVERY TO BE SEMI AUTOMATED, THAT'S THE HOPE AND HOPEFULLY MINIMIZING HUMAN BIAS, ALLOWS A LARGE DIVERSE SEPARATED TEAMS TO COMMUNICATE AND EFFECTIVELY WORK TOGETHER AND AT THE BOTTOM I LISTED SOME OF THE TECHNOLOGY THAT'S BEHIND WATSON. THAT WAS A PRETTY EXPENSIVE SYSTEM TO BUILD AND MAINTAIN. IBM IS DOING THE BEST -- IT'S REALLY GOING FULL FORCE INTO THE SPACE OF DOING THESE TRANSLATORS, I'M SORRY, WATSONS, IN DIFFERENT APPLICATIONS. THAT'S SIMILAR BUT WE DON'T WANT TO HAVE A SUPERCOMPUTER TO DO IT. WE HAVE TO FIND MORE ECONOMICAL FEASIBLE WAYS OF DOING THIS. WHAT WE'VE HIT UPON WITH THIS TRANSLATOR BLACKBOARD ARCHITECTURE IS JUST EXACTLY THAT RIGHT SOLUTION. BUT TECHNOLOGY CAN BE HARD. LOCATING THE RIGHT EXPERTISE IS SOMETIMES VERY DIFFICULT. I HAVE A STAFF OF ABOUT 80 PEOPLE, AND UNFORTUNATELY I'M ALWAYS RUNNING AGAINST THE PROBLEM THAT I DON'T HAVE THE RIGHT PERSON FOR. ENABLING US TO WORK TOGETHER AS TEAMS THROUGH THIS TRANSLATOR PROGRAM SUDDENLY I HAVE ACCESS AND I HAVE FRIENDS NOW THAT HAVE EXPERTISE THAT IS DEEPER THAN JUST THE STAFF AT RENCI. THAT'S AN AMAZING ACCELERATOR, CHANGING THE RATE WE WORKED AND THE WAY THE OTHER TEAMS HAVE WORKED. THEY ARE GEOGRAPHICALLY DISTRIBUTED, VARYING IN QUALITY, DEPENDING WHERE YOU ARE YOU CAN GET CERTAIN KINDS OF PEOPLE OR YOU CAN'T. THERE'S IP ISSUES. REPRODUCIBLE SCIENCE COMES IN WHEN YOU TALK ABOUT TECHNOLOGY. TRANSLATOR ARCHITECTURE I WON'T SPEND TIME ON BECAUSE CHRISTINE& MENTIONED IT. RIGHT NOW THE CONTROLLER WHICH IS NOTIONALLY SHOWN IN THE TOP IS WHAT THE NEW CHALLENGE IS ALL ABOUT. THE IDEA IS HOW DO WE GET ALL OF THESE INTERESTING DATA SOURCES TOGETHER TO START TO TALK ABOUT ASTHMA, AT LEAST THAT'S THE GREEN TEAM'S PERSPECTIVE BUT I'LL SLOW YOU OTHER TEAMS. POWER AND CHALLENGE OF TEAMS, DIFFERENT CRITICAL RESOURCES. PURPLE, GREEN, BLUE, RED AND ORANGE, I COULDN'T FIND A TIE WITH ALL THOSE COLORS, I'M STILL LOOKING. YOU CAN SEE ALL OF THE INSTITUTIONS THAT ARE INVOLVED IN THIS PROJECT AND THE FACT THAT THEY ARE ACTING IN INTERESTING CONCERT TO ONE ANOTHER IS JUST AMAZING TO ME. SO THE POWER OF TEAMS IS TEAMS PROMOTE THE SHARING OF EXPERTISE, TOOLS, PERSPECTIVES, ALSO LESSONS LEARNED. THERE'S BEEN MANY CASES WHERE WE'VE PICKED UP THE PHONE OR GOTTEN ONTO SLACK AND FOUND SOMEBODY FIGURED OUT SOMETHING THAT WE WERE GOING TO HAVE TO SPEND TIME AND ENERGY ON. EACH TEAM HAS A UNIQUE SET OF SKILLS, SOME IN ONTOLOGY, PROBABILISTIC MODEL, BLACKBOARD DATA, PATIENT DATA. WE'VE ASSEMBLED SIX TEAMS INCLUDING NCATS AS PART OF THE TEAM, 18 INSTITUTIONS I COUNT, AND WE VETTED THESE NUMBERS CAREFULLY WITH OUR COLLEAGUES. THREE COUNTRIES, 100 TEAM MEMBERS, 100 PEOPLE HAVE TOUCHED CODE OR TOUCHED DATA AS PART OF THIS PROJECT, EVEN THOUGH MANY OF THEM ARE NOT BEING PAID OFF THIS PROJECT. BUT INTEGRATING KNOWLEDGE SOURCES IS HARD, THE CHALLENGE OF TEAMS. PEOPLE ON TEAMS CAN BE DIFFICULT TO UNDERSTAND. IT'S BEEN SURPRISING TO ME HOW MUCH EVEN VERY TECHNICAL PEOPLE WHO ARE USING SPECIFIC VOCABULARIES MEAN VERY DIFFERENT THINGS WHEN THEY TALK ABOUT FOR& EXAMPLE AN API. OKAY? THAT TO ME HAS BEEN A REAL SURPRISE. IT'S ONE THING TO HAVE RELATIVE HARMONY IN YOUR BUILDING WHAT YOU MEAN BUT IT'S SHOCKING TO FIND OUT YOU'RE TALKING ABOUT TWO DIFFERENT THINGS EVEN THOUGH YOU SPENT AN HOUR TALKING ABOUT AN API. SO THESE ARE PEOPLE GEOGRAPHICALLY DISTRIBUTED, YOU'D NEVER KNOW THIS IN YOU DID NOT SPEND TIME IN A ROOM WITH THEM. OF COURSE THEY ARE SENSITIVE AND LICENSED IN THE SENSE THEY HAVE I.P. ISSUES TYPICALLY AND THIS IS SOMETHING THAT OCCURRED DURING THE PROCESS OF BUILDING THESE SLIDES. WE'LL HAVE TO THINK ABOUT HOW TO RECORD THE PROVENANCE OF THE TEAMS AS WE START MOVING TOWARD REPRODUCIBLE SCIENCE BECAUSE SOME OF THE PEOPLE ISSUES HAVE TO BE EMBEDDED IN THIS AND FOR EXAMPLE HOW ARE WE GOING TO CAPTURE THE FACT WE ALREADY LOST FOUR PEOPLE SINCE WE STARTED UNDER A YEAR AGO OUT OF ALL THESE TEAMS? THE PEOPLE WHO ARE HIGHLY PRODUCTIVE ON THIS ARE VERY ATTRACTIVE TO INDUSTRY. SO WHICH IS WHERE WE LOST THEM TO. SO KEY DRIVERS OF SUCCESS, WHY HAS THIS WORKED SO WELL? I THINK THERE'S A NUMBER OF REASONS. ONE IS THE TEAM SCIENCE. NCATS CONVENES SCIENTISTS CAN SKILLS AND PERSPECTIVES INTO A LOOSELY FEDERATED TEAM. AND THAT LOOSELY FEDERATED HAS ALLOWED US TO WORK TOGETHER, WORK ON OUR OWN PIECE, BUT YET UNDERSTAND WELL HOW THAT PIECE FITS INTO THE GREATER WHOLE, A UNIQUE SITUATION NCATS HAS ENABLED. EVEN USE OF COLORS WAS JUST REALLY FOUNDATIONAL IDEA BECAUSE WE'RE NOT TALKING ABOUT THE CAROLINA TIME OR BROAD TEAM. WE TALK ABOUT THE GREEN TIME OF TEAM AND ORANGE TEAM. ORANGE AND GREEN TALK SO MUCH WE HAVE A FOLDER CALLED TANGERINE, OKAY? [LAUGHTER] SO BECAUSE WE INTERACT THAT EXTENSIVELY. THE OTHER TEAMS I THINK ALSO FEEL LIKE THEY ARE PART OF THE WHOLE BECAUSE OF THIS DEMOCRATIZATION OF THE WAY TEAMS ARE LABELED. I'VE STARTED DOING THAT INSIDE MY OWN ORGANIZATION NOW, WHEN I NEED TO SET UP TEAMS THAT CUT ACROSS BOUNDARIES I CALL THEM BY COLORS. IT'S AN INTERESTING PHENOMENA HOW WELL THAT ONE THING WORKED. THERE'S OTHER THINGS HERE. NCATS ENGAGEMENT HAS BEEN INCREDIBLE. CHRISTINE ALLUDED TO THE FACT THERE'S BIWEEKLY MEETINGS AND REGULAR PHONE CALLS AND A SLACK CHANNEL THAT'S GOING CRAZY. NCATS LEADERSHIP REALLY ENGAGED WITH US AND THOSE PERIODIC ASSIGNMENTS AND INTERACTIONS MADE A GREAT DEAL OF DIFFERENCE TO HOW THE STAFF FEELS ABOUT BEING ENGAGED IN THIS. THE ONE THING FOR ME TO BE EXCITED. IT'S AN ENTIRELY DIFFERENT ONE FOR THEM TO KNOW THAT CHRISTINE NOEL -- CHRIS IS PAYING ATTENTION AND THEY KNOW WHAT THEY ARE DOING IS IMPORTANT AND THEY UNDERSTAND THE CONTEXT OF THE LARGER SCIENCE THAT WE'RE TRYING TO ACHIEVE. AND I'LL SAY ANOTHER THING. TIMING HAS BEEN AN ISSUE. I DON'T THINK WE HAD DATA AND STANDARDS AND TOOLS AND NETWORKS AND COMPUTING POWER AND EXPERTISE NOT TEN YEARS AGO, MAYBE NOT FIVE YEARS AGO BUT THE TIMING WAS RIGHT TO GO AFTER THIS PROBLEM. AND THE DEMONSTRATION USE CASES HAVE BEEN JUST A TREMENDOUS WAY OF ORGANIZING OURSELVES. SO THE GREEN TEAM I'M NOT GOING TO SPEND TIME, YOU'VE SEEN THE RESEARCH FOCUS. THE ORANGE TEAM IS LOOKING AT FRANCONI ANEMIA, AND EXAMPLE QUERY FOR THIS PARTICULAR PIECE OF WORK, ORANGE TEAM IS BIG ENOUGH TO HAVE DIFFERENT PIECES IN FLIGHT RIGHT NOW. WHAT GENES, PROTEINS AND PATHWAYS ARE TARGETED BY TREATMENTS NOT WELL TOLERATED WITH PATIENTS WITH FANCONI ANEMIA OR BMF? THE BLUE TEAM, SAINT JUDE SURVIVOR COHORT RESEARCH FOCUSES LONG-TERM HEALTH OUTCOMES AMONG CANCER SURVIVORS. THEIR EXAMPLE QUERY WHAT RARE GENETIC PHENOTYPES CORRELATE, THERE'S CORRELATION BETWEEN THE TEAMS. RED TEAM IS THE TEAM OUT OF COLUMBIA, EUREKA, FOCUSING ON DEMONSTRATION AND DEVELOPMENT OF HIGH PRESSURE TESTING FRAMEWORK WHICH WE NEED TO DO THE CONTROLLER, FIND OUT WHETHER THINGS ARE WORKING. THEY ARE TRYING TO SUPPORT CONCEPT STANDARDIZATION QUERY FORMULATION, SCIENTIFIC WORK FLOW AND ANALYSIS USING REAL WORLD DATA. I SHOULD MENTION I BELIEVE ALL BUT ONE OF THE OTHER TEAMS HAS MADE A REQUEST FOR OUR DESENSITIZED DATA, HUSH+ DATA, WE'VE TRANSFERRED THAT TO JOHNS HOPKINS, THERE'S A CROSS-FERTILIZATION THAT'S REALLY FANTASTIC. ANOTHER ORANGE TEAM EXAMPLE HOW DO YOU USE FIRE TO DO DATA VALIDATION? OKAY. CROSS-TRANSLATOR QUERIES FOR INTEGRATED DATA MODELS AND PARADIGMS, I KNOW YOU ALL ARE GETTING HUNGRY SO I'LL GO QUICKLY. ORANGE TEAM HAS NLP PROJECT UNDERWAY, A BROAD USE TO ALL OF THE TEAMS, SOME ARE ALREADY EXPLORING THE ALLS OF NLP TECHNIQUES THEY ARE DEVELOPING, LOOKING AT OUR OWN PATIENT DATA AND LITERATURE DATA AROUND BIOMOLECULES, BIOACTIVITY, THINGS LIKE THAT. THE BLUE TEAM OUT OF UCSD IS LOOKING AT A WAY OF DOING HIERARCHICAL MACHINE LEARNING, DIFFERENT VARIANTS AND DRUGS THAT MUTUALLY CONVERGE ON, INTERESTING HYPOTHESIS USING MACHINE LEARNING TECHNIQUES TO LOOK AT THAT. GRAY TEAM IS RESPONSIBLE FOR BUILDING UP PROBABILISTIC GRAPH MODELS. I'LL SHOW YOU A GRAPH IN A HOW WHEN WE LOOK AT THESE GRAPHS OF RELATIONSHIPS BETWEEN DATA SOURCES HOW DO WE GO ABOUT ESTABLISHING SOME DEGREE OF CONFIDENCE THAT THE DATA ARE INDEED RELATED IN THE WAY WE THINK THEY ARE. IN ORDER TO GAIN INSIGHT INTO SAYING THERE IS A CONNECTION BETWEEN THE FACT YOU'VE BEEN EXPOSED TO A CERTAIN AMOUNT OF PARTICULATE MATTER AND FACT YOU HAVE A PARTICULAR GENE VARIANT, WHAT IS THE RELATIONSHIP? HOW DO WE TRACK THAT DOWN IN ORDER TO MAKE ALL THOSE CONNECTIONS? AND THEN FINALLY, THE OTHER THING THAT'S MADE THIS SO INTERESTED IS COMMUNICATION AND TRUST, AGAIN I MENTIONED SIX TEAMS, 18 INSTITUTIONS, ET CETERA. THIS IS A VISUALIZATION OF THE SLACK CHANNEL IF YOU GO TO THIS URL IT'S LIVE, YOU CAN LOOK AND PLAY WITH IT AND CLICK ON THINGS. WE DOING A POLL, SLACK IS JUST ONE COMMUNICATIONS MEDIUM. I SAW THREE PEOPLE WHILE I WAS SITTING HERE USING SLACK SO I KNOW A LOT OF US ARE USING SLACK. IT'S A WAY TO DO INTERACTIONS AMONG SCIENTIFIC TEAMS ALONG CERTAIN DISCIPLINARY CHANNELS, OKAY? SO WHAT WE'RE DOING IS PULLING FROM THE SLACK CHANNEL USING SLACK API EVERY NIGHT SO WE GET SOME IDEA HOW THE TEAM SCIENCE IS EVOLVING. WE HAVEN'T DONE A LOT OF ANALYSIS. WE'RE LOOKING AT E-MAIL TRAILS, AGENDAS, MINUTES FROM MEETING TO TO UNDERSTAND SOCIOTECHNICAL. WE DON'T HAVE CONCLUSIONS BUT HAVE BALL AND CHAIN PICTURES. I WOULD NOTE THE YELLOW BLOBS ARE ORANGE AND THAT'S THE ORANGE TEAM, THEY USE SLACK MORE THAN GREEN. GREEN TEAMS ARE SMALLER BUBBLES, DIFFERENT CONNECTIONS BETWEEN DIFFERENT GROUPS OF PEOPLE. I WANT TO TAKE THE TIME TO QUICKLY FLASH UP ON THE SCREEN ALL OF THE PEOPLE THAT ARE INVOLVED IN EACH OF THESE. A LOT OF THESE PEOPLE ARE PROGRAMMERS OR PEOPLE THAT DON'T KNOWSLY NECESSARILY GET ACCOLADES. I WANT TO MENTION THERE'S A VERY WIDE DIVERSE GROUP OF PEOPLE INVOLVED IN THIS PROGRAM AND I WANT TO CALL TO YOUR ATTENTION BOTH THE LENGTH MUCH -- MUCH LIST AND VARIABILITY IN THE MIDDLE. WE HAD EVERYBODY LOOK AT PARTICIPANTS TO MAKE SURE EVERYBODY WAS REPRESENTED AND HAD THE RIGHT TITLE, WE CROWD SOURCED. RED TEAM BIOINFORM IS, LAB COORDINATOR, POSTDOCS, SOFTWARE ENGINEER, BLUE TEAM BIOLOGISTS, PHYSICIANS, EPIDEMIOLOGISTS, GRADUATE STUDENTS, PROGRAMMERS. GREEN TEAM THAT'S MY TEAM. SO I CLAIM TO BE A COMPUTATIONAL SCIENTIST, PEDIATRICS. DOWN AT THE BOTTOM IS CARL GUSTAFSON, PROJECT MANAGER ON THIS PROJECT. HE IS A BUSY PERSON. HAVING A PROJECT MANAGER ON A PROJECT THIS LARGE HE CAN COORDINATE WITH OTHER PROJECT MANAGER, KEPT ALL THE THINGS GOING AND THE MINUTES AND AGENDAS AND DETAILS ARE FLOWING SO THAT THE SCIENTISTS AND CODERS AND BIOLOGISTS CAN DO THEIR THING IN A MORE PRODUCTIVE WAY. USUALLY YOU DON'T HAVE THAT KIND OF CAPABILITY ON THESE TEAMS BUT IT'S MADE A HUGE DIFFERENCE THESE TEAMS BEING ABLE TO MESH WELL. ORANGE IS HIGHLY SKILLED, ADDITIONAL OBSERVATIONS I WANT TO MENTION I MADE MORE NOTES TO MYSELF ABOUT TRANSLATOR PROJECT. THIS PROJECT HAS DRAWN A LOT OF ATTENTION. IT'S GOT AT LEAST 5-CTAs INVOLVED, CTSAs INVOLVED, MAYBE SIX. IT IS SIX, OKAY. ORANGE TEAM HAS THREE CTSAs, AND CHRIS CHUTE IS ON THE JOHNS HOPKINS CTSA. RED TEAM THEIR CTSA IS INVOLVED WITH THEM. BLUE AFFILIATED WITH UCSD CTSA, FEEDING INFORMATION BACK IN, I'M ON OUR CTSA. OH, SCRIPPS TOO. YOU'RE RIGHT. I FAILED TO MENTION THAT. I KEEP LOOKING AT THE CLOCK. WE'RE ALREADY HALF AN HOUR OVER. I'M SORRY, SCRIPPS. THIS HAS DRAWN IN ATTENTION OF CTSAs, IT'S HAD AN IMPACT ON MY CAMPUS, NOW DISCUSSING WHETHER OR NOT WE SHOULD DO A TRANSLATOR ACROSS ALL OF THE INSTITUTIONS ON THE CAMPUS, ALL OF THE ORGANIZATION ALSO. SO WHY CAN'T WE HOOK UP ALL OF THE KNOWLEDGE SOURCES ON OUR CAMPUS? THIS IS SHOWING US THE WAY. ANOTHER EXAMPLE IS WE JUST -- THERE'S A SMALL MODEST AMOUNT OF MONEY, A COUPLE MILLION DOLLARS DEVOTED EVERY YEAR TO SPURRING ON RESEARCH FOR THE STATE OF NORTH CAROLINA. IT'S COMPETED AMONG JUST IN THE STATE OF NORTH CAROLINA AND THE GROUP THAT WON THAT CONCENTRATION OF FUNDING IS LOOKING AT RARE DISEASES ACROSS NORTH CAROLINA. AND THEY ARE USING THE SAME TECHNIQUES TO APPLY FOR THAT FUNDING AND THEY WERE THE SINGLE-FUNDED ENTITY IN THE STATE OF NORTH CAROLINA SO THERE'S NOW GOING TO BE SOMETHING THAT LOOKS LIKE THE TRANSLATOR FOCUSED ON RARE DISEASES IN NORTH CAROLINA. AND THAT'S ALL BEEN FUNDED BY THE STATE OF NORTH CAROLINA BECAUSE THEY THINK THIS IS REALLY INTERESTING STUFF. WE MENTIONED THE HACK-A-THONS, THAT'S ANOTHER REASON FOR SUCCESS, GETTING TOGETHER, KNOW PEOPLE, BREAK BREAD, EXCHANGE. THE SECOND HACK-A-THON WE'RE GOING TO DO THINGS IN IS GOING TO BE IN OCTOBER, CHRISTINE MENTIONED, YOU SAW HOW TO LOOK AT THAT. AND THEN FINALLY I WANT TO END BY SAYING THE FOLLOWING. WHEN CHRIS FIRST BRIEFED YOU ON THIS, I WATCHED THE PRESENTATION, HE MENTIONED NINE OBJECTIVES. OKAY. THIS PROGRAM HAD. SO IT'S OBJECTIVE 4 AT THE TOP, THEN 8, THEN 1. WHAT I DID IS I POLLED 15 P.I.s OR SENIOR LEADERS IN AMONG THE TEAMS AND ASKED HOW WELL ARE WE DOING? CAN YOU ASSESS OUR SUCCESS? AND THIS HAS BEEN ARRANGED BY THE LONGER THE BLUE BAR, THE BETTER WE'RE DOING. THE IDEA WAS GIVE US A 5 IF WE'RE DONE. 4 FOR WELL UNDERWAY. 3 IF WE MADE GOOD PROGRESS. 2 WE'VE DISCUSSED AND 1 IS NOT STARTED. I DIDN'T PUT ERROR BARS BUT CAN GIVE THEM TO YOU IF YOU WANT THEM. THIS IS AN IDEA OF OUR SELF ASSESSMENT HOW WELL WE'RE DOING AGAINST NINE OBJECTIVES AND ADDED ONE OTHER OBJECTIVE WHICH IS HOW WELL ARE WE DOING ON TEAM SCIENCE? THAT ISN'T AN OBJECTIVE AND IT'S NOT LABELED BUT WE GOT A PRETTY STRONG INDICATOR FROM AT LEAST THOSE 15 PEOPLE THAT ARE -- I'M SORRY, IT WAS 11 PEOPLE OUT OF 15 THAT I ASKED TO TAKE IT, PRETTY GOOD RESPONSE THIS IS GOING WELL. I THOUGHT THAT WAS AMAZING AMONG PEOPLE TYPICALLY PREDISPOSED TO LOOK AT EVERY TEAM ISSUE AS SOMETHING THAT THEY WISH THEY DIDN'T HAVE TO BE BOTHERED WITH BECAUSE THEY WANT TO JUST DO THEIR SCIENCE OR ENGINEERING OR TECHNOLOGY. WITH THAT, I'LL SEE IF YOU HAVE QUESTIONS. THANK YOU. >> I THINK ALL OF US HAVE THE SAME REACTION, WHICH IS WOW! THIS IS JUST INCREDIBLE. AT THE RISK OF GOING BACK TO CHIPS IN SPACE, I'M REALLY OVER THE MOON ABOUT THIS PROJECT. >> GOOD. >> FOR ALL KINDS OF REASONS. BUT I REALLY AM EAGER TO HEAR WHAT THE COUNCIL HAS TO SAY. >> THIS IS FANTASTIC. I'M GLAD TO SEE. A COUPLE THOUGHTS. I THINK ABOUT OPPORTUNITIES FOR OTHER DATABASES. AND SO I DON'T SEE THE DATABASES FROM INSURERS, MEDICAID, COMMERCIAL INSURANCE, 155 MULTI-PEOPLE WHO HAVE EMPLOYER -- SOME TYPE OF INSURANCE, THINK ABOUT THE PERCENTAGE OF PEOPLE WHO HAVE MEDICAID, OR MEDICARE. THOSE ARE DATABASES THAT CLAIM DATA, SHOULD BE DATABASE THAT WE'RE TAPPING INTO. HAVE WE NOT HAD SUCCESS WITH IMPACT AND GETTING ENGAGED WITH THEM? >> SO I THINK I HAD IT LISTED ON ONE OF THE SLIDES BUT SO FAR WE'VE HOOKED UP 44 KNOWLEDGE SOURCES, 44 DATABASES, IF YOU WILL. AND WE ARE LOOKING FOR A WAY THAT WE CAN INCLUDE MORE KNOWLEDGE SOURCES. AND WE CERTAINLY HAVE TALKED AOUT ALL OF THE KNOWLEDGE SOURCES YOU JUST LISTED. INTERNALLY WE KNOW THOSE ARE RICH SOURCES OF INFORMATION. THERE ARE LICENSING ISSUES AND PART OF THE CHALLENGE HERE IS WE'D LIKE TO MAKE AS MUCH OF THIS OPEN SOURCE AS POSSIBLE. WE'LL HAVE TO FIGURE OUT HOW WE CAN INCENT PEOPLE WHO OWN VERY USEFUL DATA, WHAT IS THE MECHANISM TO ALLOW THEM TO INCLUDE DATA THAT WE MUTUALLY BENEFIT. WE'LL HAVE TO FIGURE OUT HOW TO WORK AROUND PROSECUTES BUT IT'S AN ACTIVE AREA OF DISCUSSION. >> STAN, THANK YOU VERY MUCH. INSPIRING AND TIMELY AS YOU POINTED OUT. TIMELY BECAUSE JUST TO ADDRESS THE SOURCE OF DATA AND DELIBERATION OF DATA SOMETHING WE HAVE TO TACKLE. HEALTH DATA HAS TO BE LIBERATED BECAUSE WE ALL HAVE THEM, AND WE ALL ACTUALLY CONTROL THEM, AND WE NEED TO FIND GOOD WAYS OF MAKING THEM ACCESSIBLE, NOT JUST OUR OWN BENEFITS BUT TO THE GREATER GOOD. FOR THAT, THIS EXAMPLE OR THIS MODEL DEVELOPMENT, DEMONSTRATING IS SIGNIFICANT BECAUSE IT WILL ILLUSTRATE GAPS AND OPPORTUNITY, DIRECT AND INDIRECT WAYS. FIRST OF ALL, THANK YOU VERY MUCH. SECONDLY I THINK IT'S A VERY IMPORTANT PROGRAM THAT NEEDS TO BE EMPOWERED. ALSO THROUGH NIH, IN OTHER WAYS, IF POSSIBLE. IT ALSO PERHAPS CAN BUILD THE FOUNDATION FOR HONEST DATA BROKERS THAT PATIENTS CAN -- INDIVIDUALS CAN GIVE THE PERSONAL HEALTH DATA FIRST OF ALL TO ORGANIZE THEM, STRUCTURE THEM, IN A MEANINGFUL WAY SO THEY ARE TRULY COMPATIBLE, ACCESSIBLE, EXCHANGEABLE AND REUSABLE. AND I THINK THERE'S A LOT OF CRITICAL MASS AROUND, BUT THE QUESTION IS HOW MUCH THE TRANSCELERATOR CAN PLAY A ROLE IN MAKING IT HAPPEN, A SOCIETAL SHIFT, SOMETHING TO DO WITH OWNERSHIP, ALSO SOMETHING TO DO WITH RESPONSIBILITY, AND DISRUPTION OR BREAKING EVERYTHING THAT HAS EXISTED BEFORE. AND THERE ARE SOME MEMBERS IN SOCIETY OR INTEREST GROUPS THAT WILL FALL SHORT RELATIVELY AT LEAST IN THEIR OWN MIND AND THAT'S WHY THIS INTEGRATION AND DISCUSSION ARE MAKING IT AN OPEN DIALOGUE THAT'S TRANSPARENT ENGAGES IS VERY CRITICAL, IT'S A VERY CRITICAL CONCEPT. I'M FROM THE AGENCY SIDE, WE HAVE A GREAT INTEREST, NUMBER ONE. NUMBER TWO HAVE IMMINENT NEEDS BECAUSE OTHERWISE WE CAN'T ACCESS DATA WE NEED. THIRDLY SOME IDEAS HOW TO BE PART OF IT IN A SENSE THAT WE WILL GET DATA IN A DIFFERENT WAY AND WE'LL HAVE ACCESS TO DATA IN A DIFFERENT WAY, WHICH IS TRULY CRITICAL TO MOVE MEDICINE FORWARD. >> OTHER QUESTIONS? >> I WAS JUST GOING TO SAY THIS IS REALLY VERY COOL, VERY COOL STUFF, THAT YOU'RE BUILDING. A COUPLE OF COMMENTS. ONE IS THAT, YOU KNOW, OBVIOUSLY SOME OF THE VALIDITY OF THIS DATA IS NOT ALWAYS BELLWETHERRED, YOU COULD HAVE A LOT OF DATA BUT DATA COULD BE TOTALLY UNRELIABLE, ESPECIALLY IN THE ELECTRONIC HEALTH RECORDS AND VARIETY OF OTHER SOURCES. SOME OF THE ENVIRONMENTAL DATA MIGHT BE BETTER ACTUALLY BUT YOU DON'T KNOW. I THINK THAT'S ONE CHALLENGE THAT WE ALL HAVE TO CONSIDER. THE SECOND IS THERE'S A LOT OF REGULATORY BARKERS, AS YOU SORT OF ALLUDED TO, BUT SOME OF THOSE ARE EVEN AT THE STATE LEVEL, AS OPPOSED TO ANYTHING WE CAN DO, EVEN AT THE FEDERAL LEVEL. SO THERE'S GOT TO BE A LOT MORE ENGAGEMENT OF THE LOCAL GOVERNMENT, THE STATE GOVERNMENT, FOR EXAMPLE, AND OUR STATE. WE HAVE FINALLY GOTTEN APPROVAL TO GET ACCESS TO SCHOOL DATA, GET ACCESS TO PRESCRIPTION DATA. THOSE KINDS OF THINGS THAT ARE VERY CRITICAL FOR CERTAIN TYPES OF INQUIRIES. SO WHILE THIS IS A GREAT DEMONSTRATION PROJECT, YOU KNOW, AGAIN, I THINK THIS WILL OPEN UP A LOT OF OPPORTUNITIES TO CLEAN UP VARIETY OF OTHER PROCESSES. >> I TOTALLY AGREE. I PERSONALLY THINK, AND I DON'T WANT TO BE TOO EXPANSIVE, THAT IS A TRANSFORMATION OF THE WAY WE DO SCIENCE, THROUGH MASSIVE USES OF DATA WELL CURATED AND WELL UNDERSTOOD. AND SOME OF THAT CURATION AND UNDERSTANDING IS NOW A MANUAL PROCESS, IT'S A TIME CONSUMING PROCESS. WHAT WE'RE HOPING TO EMERGE, AND WE ALREADY SEE SOME OF IT, IS TOOLS THAT ALLOW YOU TO DO SOME OF THAT AUTOMATICALLY OR SEMI-AUTOMATICALLY. AND THAT HAS OCCURRED IN THE LAST FEW YEARS. I WOULD ALSO SAY THAT THE REGULATORY ISSUES ARE VERY THORNY ISSUES THAT WE HAVE TO FIGURE OUT HOW TO ADDRESS, BECAUSE IF WE CAN'T SHARE DATA THAT HAS REAL VALUE WHEN COMBINED WITH OTHER COLLECTIONS THEN WE'RE REALLY NOT DOING THE PUBLIC SERVICE WE SHOULD. THIS SHOULD BE FOR THE PUBLIC GOOD. AND WE HAVE TO FIGURE OUT HOW TO CAST WHAT WE'RE DOING AS MECHANISM BY WHICH MUNICIPALITIES OR STATE GOVERNMENTS CAN DO THINGS IN A WAY THAT IS PROTECTED AND REASONABLE AND ALLOWS THEM TO SHARE AND SEE SOME BENEFIT FROM IT. SO THE TECHNICAL ISSUES ARE CHALLENGING, BUT UNDERSTANDABLE. THE SOCIAL ISSUES, HONESTLY I THINK THIS MECHANISM THAT'S BEING PRODUCED HERE IS ONE OF THE FIRST I'VE SEEN OF LOOSELY FED RATING THESE DATASETS, CREATING A PICTURESI PICTURE BY WHICH YOU CAN ACCESS DATA. I CAN PUT MY DATA UP AND I CAN DO OF USE THAT GROUP. THAT'S ONE OF THE REASONS I STARTED BY SAYING THIS IS THE MOST EXCITING PROJECT IN MY ENTIRE CAREER. I THINK THIS IS ONE OF THESE INFLECTION POINTS WHERE WE NOW HAVE ENOUGH DATA PEOPLE CAN WRAP THEIR HEADS AROUND AND MAKE SCIENCE GO FASTER. YOU CAN APPLY THIS TO DIFFERENT DISCIPLINES. IT'S NOT JUST MEDICINE AND HEALTH. THIS MECHANISM BEING CREATED WITH TRANSLATOR SHOULD APPLY TO CHEMICS, PHYSICS, OBVIOUSLY BIOLOGY, SHOULD APPLY TO THE INSURANCE INDUSTRY. THERE'S ALL KINDS OF THINGS YOU CAN DO BY LOOKING AT PRACTICES ENABLING LARGER GROUP ACTIVITY. THAT IS TRANSFORMATIVE, BUT IT WILL BE SCARY. >> JEFF? >> QUICK QUESTION FOR CHRISTINE. I LOVE THE WAY YOU SET UP YOUR DATA TRANSLATOR. DO YOU GUYS HAVE PRIZE AUTHORITY? THIS WILL BE AN EXTRAORDINARY OPPORTUNITY FOR A PRIZE. IF YOU REALLY WANT TO GET THE HIGH SCHOOL KID, JUST A THOUGHT. THIS IS VERY PRIZABLE. >> WHEN I HEARD HER ANNOUNCE IT I THOUGHT MAYBE I DON'T WANT TO USE THIS HOUR THIS WAY. [LAUGHTER] >> STAN, I'VE BEEN PLAYING IN THIS SPACE A LITTLE BIT. AND HOW DO YOU IDENTIFY USEFUL VERSUS LESS USEFUL DATA SOURCES? SO I CAN TELL YOU I HAVE A MILLION KIDS WORD OF DATA, I USE 100,000, PAID FOR A MILLION. HOW DO YOU THINK ABOUT THAT? >> SO I DIDN'T PUT EVERYTHING IN THIS TALK I COULD HAVE. I HAD 20 PAGES OF NOTES THAT I DECIDED I WAS NOT GOING TO BE ABLE TO READ, OKAY? SO WE'VE -- THERE'S AN ACTIVE GROUP TALKING ABOUT DATA QUALITY USING FAIR T.L.C. STANDARDS, HOW CAN YOU USE MECHANISMS TO INTERROGATE THE DATA. IN ADDITION TO DATA COLLECTIONS WRAPPED BY APIs, ARCHITECTURE GROUP WORKING ON IDEAS AROUND BEACONS, ALSO PIECES OF SOFTWARE THAT CAN INTERROGATE DATA SOURCES, DATA SOURCES CAN IDENTIFY INFORMATION BACK TO THE BEACONS, AND THE BEACONS CAN ACT AS TRANSLATORS BETWEEN DATA SOURCES, NOT A FULL CONTROLLER, JUST A STEP IN THE RIGHT DIRECTION. THAT GROUP HAS DISCUSSED HOW WE CAN USE BEACONS TO INTERROGATE DIFFERENT DATA SOURCES TO EVEN DO THINGS LIKE GIVING A GRADE FOR DATA COLLECTION, A IF IT'S WELL ORGANIZED, D IF IT'S NOT. MAYBE AN F. SO THESE ARE IDEAS THAT ARE EMERGING THERE'S A LOT OF LITERATURE IN THE SPACE AND WE KNOW WE HAVE TO FIGURE OUT HOW TO AUTOMATE THESE THINGS. I'VE BEEN IN MEETINGS IN THE LAST WEEK WHERE VARIOUS DATABASES THAT WERE MENTIONED HERE TODAY, I WON'T SAY WHICH ONES, REFERRED TO AS DUMPING GROUNDS. LOTS OF TIMES AS SCIENTISTS WHEN WE GET DONE WITH A PROJECT AND WRITE THE PAPER WE DO WHAT WE'RE SUPPOSED TO DO WITH DATA, PUT IT SOMEWHERE, WE'RE NOT EAGER TO SPEND SIX MONTHS GETTING IT CLEAN AND TIDY SO SOMEONE CAN USE IT OR DOCUMENT THE LABELS. AND I USED TO GET FRUSTRATED WITH PEOPLE THAT ACTED LIKE THAT BUT THEN I REALIZED I AM HE. WE ALL DO THIS BECAUSE WE'RE BUSY PEOPLE TRYING TO DO SCIENCE, AND NOW WE'RE GOING TO HAVE A MECHANISM, THIS MECHANISM, OF SAYING, WELL, AT LEAST EXPOSE IT AND WE CAN HELP YOU FIND TOOLS TO GET IT CLEANED UP. BY THE WAY, THAT MAY MAKE IT SO YOU CAN TEAM WITH SOMEBODY AND GO AFTER AN OPPORTUNITY YOU WOULDN'T HAVE BEEN ABLE TO GO AFTER OTHERWISE. WE'RE CHANGING THE WAY PEOPLE THINK ABOUT THEIR DATA. IT'S NOT JUST STUFF YOU USE ONCE. IT'S SOMETHING YOU NEED TO DOCUMENT. ULTIMATELY WE NEED TO MAKE CITATIONS AROUND DATA AND SOFTWARE THAT CAN BE INCLUDED ON RƒSUMES. AND THERE'S ACTIVE DISCUSSIONS AT NSF AND OTHER PLACES AROUND THAT. NOW, WILL THE ACADEMY CHANGE FAST? I DOUBT IT. I'VE BEEN THERE TOO LONG. WE'RE MOVING IN THE RIGHT DIRECTION. >> WELL, I WANT TO THANK STAN AND CHRISTINE. I HAVE TO GIVE THEM A ROUND OF APPLAUSE. [APPLAUSE] IT'S AN ILLUSTRATION OF WHAT WE TRY TO DO IN EVERY PROJECT AT NCATS, WHICH IS TO CHANGE THE TERMS OF THE CONVERSATION, THAT IS JUST COMPLETELY ASK, WELL, WHY NOT DO IT THIS WAY? AND IF YOU ASK THOSE KINDS OF QUESTIONS, AND YOU CREATE THIS KIND OF TEAM THAT STAN IS TALKING ABOUT, WHAT'S SO EXCITING IS YOU SEE WHAT HAPPENS. IT'S REALLY -- I WANT TO THANK STAN ON BEHALF OF THE WHOLE -- ALL THE RAINBOW OF COLORS THAT ARE PARTICIPATING IN THIS AND KEEP IN MIND IT HASN'T EVEN BEEN A YEAR SINCE OUR FIRST MEETING, JUST INCREDIBLE. SO THANK YOU. WITH THE KNOWLEDGE THAT ALL OF OUR HUNGER HORMONE LEVELS ARE AT AN ALL-TIME HIGH, LET'S TAKE HALF AN HOUR, CAN WE ASK PEOPLE TO BRING BACK, BRING LUNCH BACK AND MUNCH DURING THE NEXT SESSION? WE'LL COME BACK AT 1:15. THANK YOU. >> DISCUSSION IN AN UNUSUAL WAY, THAT IS, RATHER THAN HAVING A BROAD DISCUSSION ASKING PETRA TO DO IN ONE HOUR WHAT THIS ENORMOUS PROGRAM IS DOING, YOU NOTICE I TOOK ON SOME OF THAT IN MY OWN DIRECTOR'S UPDATE, AND THEN WE DECIDED TO FOCUS ON A BIG ISSUE THIS PROGRAM HAS BEEN WORKING ON, WE'LL BE DOING THIS WITH OTHER EXAMPLES GOING FORWARD. SO AS YOU CAN SEE FROM YOUR AGENDA, THERE ARE FIVE SPEAKERS THIS AFTERNOON IN THREE PIECES, FIRST THE NCATS FOLKS WHO HAVE BEEN LEADING THIS EFFORT AT NCATS, PETRA KAUFFMAN AND MICHELE CULP ARE GOING TO GIVE YOU THE RATIONALE HERE AND GORDON BERNARD WHO IS AT VANDERBILT IS GOING TO TELL US ABOUT SMART IRB EX-CHANGE, AND THE SMART IRB LEADERS WHO ARE LEE NADLER AND BARBARA BEARD FROM HARVARD WILL TELL YOU ABOUT THE WHAT AND HOW OF THIS -- HOW DID THIS HAPPEN. AS WE'VE BEEN TALKING ABOUT WITH OTHER PROJECTS, WE'RE EAGER TO NOT ONLY ACCOMPLISH THINGS PREFERABLY THINGS EVERYBODY THINKS ARE IMPOSSIBLE BUT WHEN THEY SUCCEED, TO ASK WHY. WHY DID THEY SUCCEED SO WE CAN APPLY THEM TO OTHER THINGS. YOU HEARD THAT IN THE PREVIOUS DISCUSSION. SO PREVIOUS PRESENTATIONS. THE FIRST PERSON IS PETRA, AND I THINK WHAT WE'RE GOING TO DO, PETRA, TELL ME IF THIS IS RIGHT, GO THROUGH ALL THREE PIECES OF THIS AND THEN WE'LL HAVE I DON'T KNOW IF WE CALL IT A PANEL DISCUSSION BECAUSE WE DON'T HAVE ROOM FOR A PANEL BUT ASK EVERYBODY TO SIT AT THE END OF THE TABLE AND YOU SHOULD THINK ABOUT EVERY REASON THIS IS NOT GOING TO WORK, WHEN WE IMPLEMENT THIS SO WE CAN ANTICIPATE THOSE THINGS. CERTAINLY WE LOVE TO HEAR WONDERFUL THINGS, THAT TELL US HOW WONDERFUL THIS IS, CAN YOU PREFACE YOUR COMMENTS WITH THAT. WHAT WE'RE REALLY INTERESTED IN IS WHAT ARE WE NOT THINKING, WHAT ARE THE POTHOLES WE'RE GOING TO RUN INTO, WOULD BE EXTREMELY HELPFUL. PETRA, TAKE IT AWAY. >> WE'LL TRY TO CATCH UP, I WILL CUT MY PRESENTATION BY A FEW SLIDES, I'LL SKIP SOME THINGS SO WE CAN MAKE SURE WE HAVE ENOUGH TIME FOR THE DISCUSSION AND FOR YOUR FEEDBACK. I'M SO PLEASED THAT WE HAVE A CHANCE HERE TO DISCUSS WITH YOU AND SHOW YOU WHAT I THINK IS TREMENDOUS PROGRESS THE CTSA COMMUNITY HAS MADE WITH REGARDS TO STREAMLINING THE IRB PROCESS, ETHICS OF YOU PROCESS. FOR THOSE IN THE ROOM OR WATCH BY VIDEOCAST NOT AS NOT AS CLOSELY INVOLVED IN DAY TO DAY OPERATION, THIS MAY NOT SEEM EXCITING, IRB, AFTER WE HEARD ABOUT SCIENCE AND TRANSLATOR, BUT PLEASE DO REALIZE THIS IS ACTUALLY VERY EXCITING AND REALLY IMPORTANT FOR ALL OF US, NOT ONLY FOR THOSE WHO HAVE TO WORK AND IMPLEMENT ON THESE STUDIES, BUT IT MATTERS TO ALL OF US BECAUSE CLINICAL STUDIES ARE THE CRITICAL STEPS IN GETTING NEW TREATMENT TO PATIENTS. THEY ARE THE CRITICAL STEPS IN GETTING MUCH NEEDED MEDICAL EVIDENCE. WITHOUT THEM, YOU KNOW, DOCTORS WILL NOT HAVE THE INFORMATION THEY NEED AND NEW TREATMENTS WILL NOT COME FROM ALL THESE TREMENDOUS DISCOVERIES THAT YOU KNOW HAVE TO TAKE ADVANTAGE OF IN BIOMEDICAL RESEARCH. THEN I WAS IN ACADEMIA, I REMEMBER WORKING ON LOU GEHRIG'S DISEASE. ONE OF MY PATIENTS, HIS LAST HOPE WAS TO PARTICIPATE IN A CLINICAL TRIAL. AND HE WOULD COME TO CLINIC AND I WOULD HAVE TO TELL HIM THAT THE TRIAL HE WANTED TO PARTICIPATE IN WASN'T AVAILABLE YET AT OUR SITE BECAUSE IT WAS WAITING FOR IRB APPROVAL. THIS SADLY HAPPENED A COUPLE OF TIMES WHEN HE CAME BACK AND THEN FINALLY WHEN THE TRIAL OPENED UP HE WAS TOO SICK TO PARTICIPATE. AND THAT IS REALLY HEARTBREAKING AND SHOULDN'T HAPPEN. BECAUSE TRIALS ARE HOPE AND TRIALS BRING BETTER TREATMENTS TO PATIENTS AND WHEN I CAME TO THE NIH I REALIZED THIS WAS NOT JUST AN EXPERIENCE IN MY FIELD BUT THAT THIS WAS VERY PERVASIVE AND THAT IN FACT MOST NIH TRIALS HAD A START-UP TIME OF ABOUT A YEAR, AND OF COURSE THAT TIME AND THE RESOURCES COULD BE BETTER USED FOR SCIENCE ITSELF. IT'S NOT ONLY PATIENTS WHO ARE VERY FRUSTRATED WITH THIS BUT ALSO HARD FOR INVESTIGATORS BECAUSE WE WANT TO SPEND TIME SEEING PATIENTS AND DOING RESEARCH AND NOT ON ALL THE BUREAUCRATIC HURDLES. THIS IS SOME OF THE BACK GROUND TO INTRODUCE THIS SESSION I THINK AND SHOW YOU ALL IT REALLY MATTERS AND IT'S REALLY IMPORTANT. THEN WHAT HAPPENED IS FORTUNATELY THAT PEOPLE BEGAN TO REALIZE THAT THERE'S ACTUALLY NOT ONLY IS IT FRUSTRATING TO PATIENTS AND RESEARCHERS BUT ALSO DOESN'T PERHAPS ADD AS MUCH VALUE. THE FIRST PAPER STARTED TO EMERGE, AND I DON'T HAVE TO GO INTO DETAILS SHOWING ACTUALLY THESE SEPARATE REVIEWS CAUSE DELAYS, THEY DON'T NECESSARILY ADD VALUE, IN FACT THERE WAS INCONSISTENCIES WHEN THEY TESTED HOW THE SAME PROTOCOL WAS VIEWED AT DIFFERENT PLACES AND EVEN WAS THE POSSIBILITY RAISED OR QUESTION WAS RAISED BY JERRY MENIKOFF OVER THE TIME DISTRIBUTED ACCOUNTABILITY COULD ACTUALLY BE LESS SAFE HAVING ACCOUNTABILITY IN ONE PLACE. SO CULTURE STARTED TO CHANGE AND FDA WAS ALMOST AHEAD OF THIS ALREADY IN 2006, ISSUING GUIDANCE THAT ONE IRB REVIEW DID NOT HAVE TO BE REVIEWED REPEATEDLY OVER AND OVER AND THEN ALL THESE RESULTS OF REVIEW HAVING TO BE RECONCILED OHRP SUPPORTED THIS IN 2010. I WORKED WITH THE INITIATIVE THAT CAME TO THE CONCLUSION THAT IT WAS PREFERRED IN THE BEST INTEREST OF PATIENTS AND SCIENCE TO HAVE A SINGLE IRB REVIEW AND THIS HAS FINALLY COME AT THE NIH POLICY THAT MICHELE WILL TELL YOU MORE ABOUT. THAT'S FOR SOME BACKGROUND. WHY DID IT NOT ALREADY HAPPEN? WHY DID IT TAKE SO LONG? THE REASON IS THERE'S VERY GOOD ISSUES IN TERMS OF THINGS THAT HAVE TO BE ADDRESSED AND THAT CAUSED RELUCTANCE AMONG INSTITUTION, ONE OF COURSE IS LIABILITY, THEN ADMINISTRATIVE CHALLENGES THAT COME WITH SUCH A CHANGE, POSSIBLE CONFUSION OF RESPONSIBILITY, WHAT DOES THIS MEAN, THERE HAS TO BE A CLEAR SEPARATION. YOU'LL HEAR MUCH MORE ABOUT THIS FROM THE SPEAKERS, A CLEAR UNDERSTANDING OF WHAT THE RELYING INSTITUTION DOES. SO THE INSTITUTION THAT SAYS WE DEFER IRB REVIEW TO SOMEBODY ELSE AND WHAT THAT REVIEWING IRB HAS TO BE AGREED UPON AND YOU LEARN MORE ABOUT THE GREAT WORK HAPPENING IN THIS REGARD. THERE'S ISSUES THAT WILL MAYBE TAKE MORE TIME TO ADDRESS WHICH IS THE TRUST INSTITUTIONS AND INVESTIGATORS HAVE TO FEEL COMFORTABLE RELYING ON ANOTHER IRB, AND THEN OF COURSE THE VERY IMPORTANT ISSUE THAT LED ORIGINALLY TO THE CONCEPT OF IRB REVIEW HAVING TO BE LOCAL, WHICH WAS THAT THERE WOULD BE DIFFERENT LOCAL CONTEXT, OF COURSE AS SOME OF THESE PUBLICATIONS THAT I MENTIONED EARLIER HAVE SHOWN, THAT KIND OF LOCAL CONTEXT IS ACTUALLY NOT, YOU KNOW, DIFFERENT IN DIFFERENT PLACES AS PERHAPS ORIGINALLY THOUGHT FOR MOST STUDIES, AND FINALLY THERE'S VERY UNDERSTANDABLE CONCERN AT THE ACADEMIC INSTITUTIONS AND HOSPITALS IN TERMS OF WHAT BURDEN WOULD BE ASSOCIATED WITH THE CHANGE AND THEN ALSO WITH BEING REVIEWING IRB OR RELYING ON SOMEBODY ELSE'S IRB. AND THESE ARE ALL I THINK IMPORTANT ISSUES THAT HAVE TO DO WITH THE IMPLEMENTATION DISSEMINATION OF A SINGLE IRB MODEL THAT THE CTSA ROLE CAN HELP THE COMMUNITY ADDRESS THIS NOW THAT THE NIH POLICY WILL COME INTO EFFECT SO A REALLY CLEAR ROLE THAT I THINK NOBODY COULD BETTER ADDRESS THAN THE CTSA COMMUNITY. AS YOU KNOW, WE HAVE A NUMBER OF SOLUTIONS ALREADY, INSTANCES OF A SINGLE IRB. SINGLE IRB MEANS ONE IRB REVIEWS THE STUDY, A CENTRAL IRB IS ONE PARTICULAR INSTANCE OF THAT. WE HAVE EXAMPLES HERE AT THE NIH WITH THE CANCER IRB AND NCI IRB, AS WELL AS AT THE V.A. THERE'S A SINGLE IRB FOR SOME OF THE V.A. STUDIES. HERE AT THE NIH ALSO WITH NEURO NEXT, I'LL TELL YOU ABOUT THAT, COMMERCIAL IRBs EXISTED FOR A LONG TIME, INSTANCES OF SINGLE IRBs. ANOTHER WAY OF IMPLEMENTING IS RELIANCE MODEL, INSTITUTIONS CAN AGREE TO RELY ON EACH OTHER'S IRB REVIEW. ONE EXAMPLE I'M FAMILIAR WITH, AT THE NIH, A SAFE TOOL CLINICAL TRIAL NETWORK USE A CENTRAL IRB, IRB HAPPENED TO BE AT MASS GENERAL, BARBARA'S TEAM WAS HELPFUL IN PIONEERING THIS. AND WE SHALL OF WE WERE ABLE TO ESTABLISH RYE LIANCE AGREEMENTS WITH THESE 25 SITES HERE, AND WE WERE ABLE TO GET SOME EARLY GOOD EXPERIENCE INDEED CUT DOWN START-UP TIME OF TRIALS SIGNIFICANTLY. OTHER EXAMPLES WE FOUND IN THE CTSA PROGRAM, THESE ARE ONLY EXAMPLES IN WISCONSIN WHERE DIFFERENT UNIVERSITIES AND HOSPITALS IN THAT STATE HAD STARTED SUCCESSFULLY RELYING ON EACH OTHER AND OF COURSE HARVARD CATALYST, THEY HAD A MUCH LARGER NETWORK OF RELIANCE, AND IN CALIFORNIA ALSO WHERE THE STATE UNIVERSITIES STARTED RELYING ON EACH OTHER. A LOT OF GREAT EXPERTISE IN THE CTSA PROGRAM, IRB AT VANDERBILT WAS IN PLACE, SINGLE IRB OR IRB RELIANCE GROUPS IN TEXAS, NEW MEXICO. SO THE ISSUE HOWEVER IS IF YOU HAVE FOR EXAMPLE ONE IRB THAT REVIEWS LIKE THIS BLUE IRB, THIS LARGER BLUE AREA HERE, THESE DIFFERENT INSTITUTIONS RELY ON THIS IRB, THAT WORKS, RIGHT? THERE'S ANOTHER STUDY IN A HAS THIS ORANGE IRB, AND DIFFERENT PLACES RELY ON THIS ORANGE IRB. IF YOU HOWEVER ARE A PLACE THAT HAS TO RELY ON IRB IN THIS NETWORK AND THAT NETWORK DIFFICULTY BECOMES OBVIOUS. BECAUSE ONCE YOU HAVE TO USE MANY DIFFERENT RELIANCE AGREEMENTS, DIFFERENT SOPS, DIFFERENT MODELS, IT BECOMES CONFUSING AND THERE'S A LOT OF ROOM FOR ERROR AND THAT'S ONE OF THE THINGS WE WANT TO AVOID IN THE CTSA PROGRAM. WE GOT TOGETHER. THERE WAS DECISION MADE TO NOT HAVE DIFFERENT REGIONAL IRBs AND HAVE A NEW WORLD THAT COULD BE EVEN MORE COMPLEX THAN THE OLD ONE BECAUSE RATHER THAN HAVING FOR EACH STUDY 100 IRBs, 100 SYSTEMS OF RELYING ON EACH OTHER SO THE GREAT ACCOMPLISHMENT YOU HEAR ABOUT NOW IS REALLY THAT THE CTSA COMMUNITY CAME TOGETHER AND SAID WE WILL HAVE A NATIONAL SYSTEM THAT WE CAN ALL -- LIKE A PLATFORM WE CAN ALL CONNECT TO. AND THIS IS WHAT HAPPENED HERE INITIALLY WITH THE IRB RELY IN WHICH MANY OF YOU AND ALL P.I.s I THINK WERE INVOLVED. AND THEN I'LL SKIP THIS. AND THEN NOW WITH THE INITIATIVES THAT YOU HEAR ABOUT SHORTLY, SO I'LL HAND IT OVER TO MICHELLE BUT IN SUMMARY TO SAY THERE'S BEEN DRAMATIC CHANGE IN LANDSCAPE AND CULTURE IN FAVOR OF THIS WHICH WILL HELP ACCELERATE PROGRESS. WE HAVE A NUMBER OF DEMONSTRATION PROJECTS AT THE NIH, CERTAINLY COMMERCIAL IRBs AND OTHERS THAT SHOW IT CAN BE DONE AND WE HAVE HOWEVER ALSO, YOU KNOW, SOME CAVEATS THAT I THINK WILL PROBABLY COME UP IN THE PANEL DISCUSSION, ONE IS THAT THE IRB APPROVAL TIME IS ONLY ONE FACTOR IN WHAT LEADS TO THE DELAYS IN START-UP. THERE ARE OTHER THINGS ANCILLARY REVIEWS SUCH AS RADIATION SAFETY, PEDIATRIC REVIEW AND SO ON THAT CAN CAUSE DELAYS AND THAT ARE OFTEN DONE STILL LOCALLY, SO MAYBE FOR US SOMETHING TO THINK ABOUT AS A NEXT STEP HOW WE CAN WORK ON THAT. ANOTHER IMPORTANT AREA ALSO IS THAT AS I MENTIONED EARLIER HARMONIZATION IS CRITICAL, IT WOULD BE VERY DIFFICULT FOR EVERYBODY TO DEAL WITH HAVING MANY, MANY DIFFERENT MODELS IN TERMS OF IRB RELIANCE, I THINK THAT'S WHAT YOU'LL HEAR ABOUT, HOW CAN WE CONTINUE TO PROMOTE THIS SORT OF, YOU KNOW, STRENGTH OF THE CTSA PROGRAM THAT THERE BE CONTINUE EFFORT TO HARMONIZATION TO KEEP A STREAMLINED SYSTEM AND WE NEED TO FIND OUT A SUSTAINABLE ECOSYSTEM, HOPEFULLY WE CAN DISCUSS WHEN WE COME TO THE PANEL THAT CAN HAVE THE CAPACITY BUT ALSO FLEXIBILITY TO MEET THE DEMANDS AS THEY PROBABLY ARISE AND CHANGE. AND FINALLY SOMETHING YOU'LL HEAR FROM INVESTIGATORS ABOUT, GREAT NEED AT THE NIH HERE WHEN WE HEAR FROM INVESTIGATORS AND NIH COLLEAGUES FOR TRAINING INFORMATION, EDUCATION, THERE'S A LOT OF UNCERTAINTY, ANXIETY IN THE WAY THAT COMES TO SEE NEW POLICY AND WHAT ITS IMPLEMENTATION WILL MEAN SO THIS WILL BE ANOTHER IMPORTANT TOPIC FOR US TO DISCUSS WHEN WE TALK ABOUT NEXT STEPS. I'LL HAND IT OVER TO MICHELE WHO WILL TELL YOU MORE ABOUT SINGLE IRB POLICY. >> THANK YOU FOUR LAYING -- FOR LAYING OUT YOU THE CHALLENGES. I'M APPRECIATIVE TO WORK AT NCATS TO WORK ON THIS INITIATIVE. I'VE SPEND TIME IN THE OFFICE OF NIH SCIENCE POLICY ON THE NIH SINGLE IRB POLICY. IT'S GREAT FOR ME TO WORK WITH NCATS AND WORK WITH GREAT COLLEAGUES TO FIGURES OUT WAYS TO IMPLEMENT AND PROVIDE SOLUTIONS TO MAKE THIS WORK. I THINK SOME OF YOU HOPEFULLY ALL OF YOU ARE AWARE THERE'S AN NIH SINGLE IRB POLICY ANNOUNCED EARLIER IN THE YEAR, AND THIS HAS BEEN IN DEVELOPMENT FOR A COUPLE OF YEARS, MAYBE 3 YEARS OR SO, WHETHER WE -- THE NIH PUT OUT REQUESTS FOR COMMENTS, RECEIVED LOTS OF COMMENTS, COMMENTS WERE ADDRESSED. THERE WERE OVERWHELMING SUPPORT FROM INVESTIGATORS FOR SINGLE IRB REVIEW OF MULTI-SITE RESEARCH. IRB ADMINISTRATORS HAD A SLIGHTLY DIFFERENT PERCEPTION OR IDEA ABOUT HOW THIS WOULD WORK BECAUSE THERE ARE A NUMBER OF ADMINISTRATIVE CHALLENGES TO NEED TO BE WORKED OUT TO MAKE THIS HAPPEN. I'M FORTUNATE TO WORK WITH COLLEAGUES AND A NUMBER OF EXPERTS ACROSS THE COUNTRY WHO ARE REALLY TALKING ABOUT HOW THEY CAN SOLVE THOSE CHALLENGES OF ADMINISTRATIVELY HANDLING A SINGLE IRB REVIEW OF MULTI-SITE RESEARCH. SO THE POLICY IS OUT. THE POLICY WILL BE EFFECTIVE JANUARY OF 2018 FOR THOSE GRANTS RECEIVED AT THAT TIME. IT WILL -- THE GOAL OF THE POLICY TO ENHANCE AND STREAMLINE IRB REVIEW PROCESS FOR MULTI-SITE RESEARCH AND PETRA DESCRIBED THAT PROCESS CAN TAKE UP WARD OF A YEAR SOMETIMES FOR MANY, FOR MULTIPLE INSTITUTIONS TO REVIEW THE STUDY AND COME BACK WITH COMMENTS AND WE DON'T KNOW WHETHER IT REALLY ACTUALLY OFFERS ANY BENEFIT OR ADDITIONAL PROTECTIONS OF HUMAN SUBJECTS. SINGLE IRB POLICY AIMS TO HAVE HIGH STANDARDS FOR HUMAN SUBJECT PROTECTIONS, IT ALLOWS FLEXIBILITY TO WORK EXPEDITIOUSLY SO THAT ONE CAN SELECT AN APPROPRIATE IRB FOR THE TYPE OF RESEARCH THAT'S TO BE DONE. WE BELIEVE THE SINGLE IRB POLICY WILL ELIMINATE UNNECESSARY DUPLICATIVE REVIEW, SO INSTEAD OF HAVING THE SAME STUDY REVIEWED BY MULTIPLE IRBs, THAT MAY HAVE THE SAME OUTCOME, WHY NOT HAVE ONE IRB AND THEN HAVE IT FINISHED AND MOVE ON. AND IT'S COMPATIBLE OF COURSE WITH THE COMMON RULE THAT WAS RELEASED, AND THAT PART OF THE COMMON RULE FOR SINGLE IRB REVIEW WILL BE EFFECTIVE IN JANUARY 2020. SO A LITTLE BIT OF INFORMATION ABOUT THAT POLICY, IF YOU WANT TO LOOK IT YOU WERE AND IF YOU WANT TO LOOK AT THE DATES, JANUARY 25, 2018, WHEN IT WILL BE EFFECTIVE FOR GRANT APPLICATIONS AND CONTRACT PROPOSALS. I WILL SKIP THIS FOR TIME PURPOSES. PETRA MENTIONED A LITTLE BIT ABOUT CENTRAL IRB AND SINGLE IRB. WE GET A LOT OF COMMENTS ABOUT THIS AND NOMENCLATURE. WHAT DO WE TALK ABOUT WHEN WE SAY SINGLE IRB, AND THEN THE SAME SENTENCE USE THE WORD CENTRAL IRB. SO FROM OUR PERSPECTIVE AT THE NIH, A SINGLE IRB IS SELECTED ON THE STUDY BY STUDY BASIS. IT'S USUALLY AN EXISTING IRB, MAYBE AT ONE OF THE ACADEMIC INSTITUTIONS, SOMETIMES WHERE THE LEAD P.I. RESIDES, AND THAT PARTICULAR IRB WILL BE THE REVIEWING IRB FOR THAT ONE MULTI-SITE STUDY. THERE ARE CENTRAL IRBs IN PLACE AS PETRA MENTIONED, NCI CENTRAL AND NEURO NEXT IRB THAT SERVES A NETWORK OR CONSORTIUM OF INVESTIGATORS TO REVIEW A TYPE OF STUDY, SO FOR EXAMPLE CENTRAL IRB, AND THE CENTRAL IRB, PROVIDING SINGLE IRB SERVICES FOR MULTI-SITE STUDIES COMING THROUGH THE TRIAL INNOVATION NETWORK. WHAT HAS NCATS DONE TO IMPLEMENT SINGLE IRB POLICY? AS THE POLICY WAS BEING DEVELOPED, NCATS WAS VERY ACTIVELY WORKING ON SOLUTIONS, ACTUALLY MAYBE EVEN BEFORE THE POLICY WAS PUT OUT. THEY WERE WORKING ON SOLUTIONS FOR HOW TO MAKE THIS PROCESS MORE EFFICIENT. THE ISSUE THAT THEY FELT THEY COULD RESOLVE WAS THAT PROCESS OF MULTIPLE ORGANIZATIONS REVIEWING THE SAME RELIANCE DOCUMENT AND MAKING MINOR CHANGES IN THE LEGALESE. PARDON ME, BARBARA, YOU'LL SAY IT MORE ELOQUENTLY. MAKE MINOR CHANGES TO THE DOCUMENT TO SUIT INSTITUTIONAL PREFERENCES BUT NOT MAKING A SIGNIFICANT CHANGE TO THE DOCUMENT ITSELF. SO AS CENTRAL IRBs WERE BEING FORMED, THEY WERE COMING UP WITH THEIR OWN RELIANCE DOCUMENT. THEY THOUGHT THIS MIGHT PERPETUATE THE PROCESS OF MULTIPLE AGREEMENTS. THROUGH AN NCATS INITIATIVE, A SINGLE RELIANCE OR AUTHORIZATION AGREEMENT WAS BUILT. WE HAVE DEVELOPED THE NCATS SMART IRB RELIANCE PROGRAM, STREAMLINED, MULTI-SITE ACCELERATED INFORMATICS, HARMONIZATION. I'LL SKIP OVER THIS. I WANTED TO BRIEFLY INTRODUCE WHAT YOU WILL BE HEARING MORE ABOUT IS THE NCATS SMART IRB MASTER COMMON RECIPROCAL IRB AUTHORIZATION RECIPROCAL AGREEMENT, AKA RELIANCE AGREEMENT. THIS WAS VETTED ACROSS THE CTSA PROGRAM, IT WAS PILOTED THROUGH AN INITIATIVE WITH PCORI, AND WAS VERY WELL INFORMED HOW THE DOCUMENT WORKED, WHAT THINGS NEED TO BE CHANGED, AND AS A RESULT OF IT LAST YEAR AROUND OCTOBER IT WAS DISSEMINATED TO CTSA INSTITUTIONS AND AS OF JANUARY THIS YEAR ALL OF THE CTSA INSTITUTIONS SIGNED ON TO THAT AGREEMENT. SMART IRB RELIANCE SYSTEM IS A TOOL DEVELOPED THROUGH THE SMART IRB INITIATIVE AT HARVARD TO PROVIDE AN ELECTRONIC TOOL TO HELP INSTITUTIONS DOCUMENT THE PROCESS OF DETERMINING WHICH IRB WILL BE THE REVIEWING IRB, AND THOSE PARTICIPATING INSTITUTIONS TO AGREE TO SEED TO THAT IRB. SO THERE IS AN ONLINE TOOL, YOU'LL HEAR MORE ABOUT THAT, THAT HELPS WITH TRACKING OF THIS PROCESS AND ALSO PROVIDES RESOURCES AND TOOLS THROUGH THAT PROCESS. IN ADDITION THE TRIAL INNOVATION NETWORK WAS STOOD UP A YEAR AGO AND INCLUDES THREE CENTRAL IRBs AND THOSE ARE THE DUKE UNIVERSITY VANDERBILT TIC, VANDERBILT, UTAH AND HOPKINS. WORKING WITH OUR COLLEAGUES AT HARVARD, WE'RE LOOKING AT A NUMBER OF WAYS TO HELP SITES SIGN ONTO THE AGREEMENT BECAUSE MORE THAN JUST THE CTSA INSTITUTIONS ARE PARTICIPATING IN MULTI-SITE STUDIES. I BELIEVE AS OF NOW WE HAVE OVER 270 INSTITUTIONS THAT SIGNED THIS AGREEMENT, INCLUDING MANY COMMUNITY HOSPITALS. THEY HAVE BEEN WORKING TOGETHER ON HARMONIZING CENTRAL IRB STANDARD OPERATING PROCEDURES, CREATING A FRAMEWORK FOR IDENTIFYING LOCAL WORK FLOWS OF HOW INFORMATION WILL BE GOING FROM LOCAL LEVEL TO THE REVIEWING IRB. AND DEVELOPING SOME PERFORMANCE METRICS TO SEE WHETHER OR NOT THE CENTRAL IRB PROCESS IS REALLY IMPROVING THE TIME LINES. IT WILL BE MAKING RECOMMENDATIONS MORE BROADLY ABOUT WHAT OUR EXPERIENCES ARE, AND ALSO LOOKING AT WAYS WE CAN HARMONIZE OUR EFFORTS IN THE SINGLE IRB PROCESS. SO THERE'S ALSO THE SMART IRB EXCHANGE, WHICH IS BEING USED THROUGH THE VANDERBILT TIC, ANOTHER ONLINE RELIANCE TOOL TO HELP INSTITUTIONS IDENTIFY WHO WILL BE THE REVIEWING IRB AND PARTICIPATING SITES AND HAS SOME TOOLS TO HELP SHARE DOCUMENTATION WITHIN THE SYSTEM, SO ONCE THE REVIEWING IRB HAS RECEIVED THE DOCUMENTATIONS, AND PROVIDED APPROVAL THERE'S A SYSTEM WHERE THE PROVIDING INSTITUTIONS CAN RECEIVE THAT DOCUMENTATION AND SHARE OTHER DOCUMENTS. YOU'LL HEAR MORE ABOUT THAT SHORTLY. SO I BELIEVE THIS COMES TO OUR QUICK SUMMARY OF WHAT IS THE VALUE OF THE NCATS SMART IRB RELIANCE PLATFORM, A NATIONAL PLATFORM THAT IS GROWING. WE HAVE MANY INSTITUTIONS THAT HAVE SIGNED ON TO THIS AND MANY THAT ARE JUST BEGINNING TO START USING THE RELIANCE AGREEMENT AND PLATFORMS PROVIDED. IT IS USEFUL FOR ANY INSTITUTION REGARDLESS OF THEIR FUNDING, WHETHER IT BE NIH FUNDING OR FUNDED BY A FOUNDATION OR COMMERCIAL SPONSORS. IT LEVERAGES EXPERTISE OF THE CTSA PROGRAM AND TRIAL INNOVATION NETWORK, BECAUSE THEY ARE ACTUALLY USING AND OFFERING INFORMATION BACK HOW TO HOW IT'S WORKING. THIS GIVES AN OPPORTUNITY TO IMPLEMENT A SINGLE AND CENTRAL IRB PROCESS THROUGHOUT THE CTSA PROGRAM. WE'RE GOING TO CONTINUE BUILDING SOME CAPACITY, AND WE THINK AS MORE INSTITUTIONS JOIN AND MORE NETWORKS JOIN THIS, THE WORD WILL SPREAD, CULTURE WILL CHANGE, AND CERTAINLY WE'LL BE SEEING A SHIFT IN THE WAY IN WHICH WE THINK ABOUT IRB REVIEW OF MULTI-SITE STUDIES. WE CONTINUE TO WORK TOGETHER TO INFORM AND HELP HARMONIZE PROCESSES ACROSS THE SINGLE IRB SPECTRUM. I AM FOR TIME'S SAKE GOING TO HAND IT OVER TO MY COLLEAGUE, GORDON BERNARD, FROM VANDERBILT, WHO WILL BE TALKING ABOUT THE SMART IRB EXCHANGE. THANK YOU, GORDON. >> IT'S A PLEASURE TO BE HERE TO TALK ABOUT THIS, SOMETHING I'VE BEEN INTERESTED IN FOR SOME TIME. THIS TIME LINE PICKS UP THE LAST 7 YEARS OF THE 10 OR 15 YEARS I'VE BEEN WORKING ON THIS. THIS SHOWS BRIEFLY HERE THAT WE STARTED OUT IN EARNEST WITH AN R 13 FROM NCRR, PREDECESSOR FOR NCATS, TO HAVE MEETINGS WITH CTSA IRB REPRESENTATIVES TO THINK ABOUT HOW WE WOULD TACKLE THIS. AND OUT OF THAT CAME IRB SHARE WHICH GOT TO THE POINT OF ONLY ONE IRB REVIEW BUT STILL MULTIPLE IRBs, SO REVIEW IS SHARED WITH IRBs BUT THEY MAINTAIN THEIR IRB OF RECORD. AND THEN THERE'S OTHER THINGS, I'LL SKIP QUICKLY, IRB CHOICE WAS SUPPORTED BY NHLBI AS A WAY TO STUDY HOW IRBs WORK WITH REGARD TO SINGLE IRBs, MULTIPLE VERSUS SINGLE IRB REVIEWS AND THAT PROJECT IS JUST WINDING UP NOW. IRB EXCHANGE WAS LAUNCHED, I'LL TELL YOU MORE IN A MINUTE. I'M GOING TO SKIP THAT ONE. WE HEARD ABOUT THE SMART RELIANCE AGREEMENT, THAT'S ESSENTIAL AND REALLY HANDOFF TO HARVARD FOR THE HERCULEAN EFFORT OF GETTING OVER 270 OR SO SITES ACROSS THE COUNTRY SIGNING ONE SINGLE RELIANCE AGREEMENT. IT'S ONLY PART OF THE ISSUE. NOW YOU HAVE AN OTHERWISE STILL COMPLEX SYSTEM OF INTERCHANGING OF INFORMATION AND I'LL GET TO THAT IN JUST A MINUTE THAT HAS TO BE MANAGED. THERE TWO DOTS ON PETRA'S MAP, IT COULD BE HUNDRED. I OVERSEE VANDERBILT. IF I HAD TO KEEP TRACK OF 100, WHAT SOPS ARE, RULES, HOW TO COMMUNICATE FOR ALL THE STUDIES WE'RE SHARING IT WOULD BE A NIGHTMARE. THAT'S BEEN THE DRIVING FORCE FOR ME OVER THE LAST 10 OR 15 YEARS TO THINK HARD ABOUT THIS PROBLEM AND HOW TO SORT IT OUT. WE BUILT IRB EXCHANGE, TRACKS RELIANCE AGREEMENTS, DOES THE BASIC FUNCTION OF TELLING YOU WHO IS RELYING ON WHO AND WHO IS THE CENTRAL IRB. OFFICIALS WITH LOG ON, DASHBOARD SCREEN, THEY CAN PICK A STUDY AND GO TO THEIR SCREEN AND PICK STUDIES FROM THAT LAST SO IT'S REALLY USER FRIENDLY TO KEEP TRACK. AND TO MY POINT ABOUT THE OTHER WORK THAT NEEDS TO BE DONE HERE SO THERE'S AN IRB REVIEW, IT'S ONLY ONE PIECE OF THE BIG PIE AND YOU CAN SEE WHAT THEY ARE, THESE ARE ALL THINGS THAT EVERY HUMAN SUBJECT'S PROTECTION PROGRAM AT EVERY INSTITUTION HAS TO KEEP TRACK OF, EDUCATORS HAVE TO BE TRAINED, DEALS WITH CONFLICTS OF INTEREST, CONTRACTS AND GRANTS, INSTITUTIONAL BIOSAFETY FOR DANGEROUS HAZARDS, PHARMACEUTICAL ISSUES, MUCH MORE THAN JUST THE IRB. WE DO HAVE A LOT MORE WORK TO DO BUT HOPEFULLY CAN BUILD THE REST OF OUR WORK ONTO THIS. THIS IS JUST -- I'M NOT GOING THROUGH THIS BUT THESE ARE THE LOCAL CONTEXT ISSUES THAT HAVE TO BE DEALT WITH STILL BY THE LOCAL IRB. EVEN THOUGH THERE'S REVIEW FOR MAIN RISK AND BENEFIT ANALYSIS, THERE ARE ALL SORTS OF LOCAL THINGS THAT NEED TO BE DONE. SO WHAT WE DID IN IRB EXCHANGE, TRIED TO CAPTURE ON A SITE SPECIFIC BASIS, WHAT STATE ARE YOU IN, AGE OF MAJORITY, HOW ARE MINORS EMANCIPATED IN YOUR STATE, WHAT RECORD KEEPING IS REQUIRED BY YOUR STATE, WHAT MANDATORY REPORTING DO YOU HAVE IN YOUR LOCALE AND SO FORTH. THOSE ARE PRETTY STATIC. THEY DON'T CHANGE OFTEN. THERE'S THE STATIC AND STUDY-SPECIFIC CONTENT, NOW YOU'RE GETTING INTO QUESTIONS LIKE WHAT ANCILLARY REVIEWS ARE NEEDED FOR THIS PARTICULAR STUDY AT YOUR PARTICULAR SITE, WHAT ARE THE RESOURCES THAT ARE NEEDED TO CONDUCT THE STUDY SAFELY AT YOUR SITE AND THE TRAINING OF THE INVESTIGATORS IN THE STUDY AND MANY MORE PIECES. THERE'S SITE AND P.I. INFORMATION, WHERE YOU GO TO CONSENT YOUR PATIENTS, RECRUITMENT PLAN, WHO IS CALLED IN AN EMERGENCY, THAT'S THE THIRD OF THE THREE COMPONENTS. HERE WE HAVE TRACKING SYSTEM. THIS COLUMN SHOWS WHICH SITE HAS SIGNED THE SMART IRB AGREEMENT, SO THEY ARE READY TO USE IT, HOW MANY SIGNED THE SMART IRB EXCHANGE AGREEMENT BECAUSE TO SE THE TOOL IS A SEPARATE PROCESS, WHICH ONES ARE SEATING REVIEW, WHETHER IT'S COMPLETE OR NOT STARTED, HOW MUCH OF THE LOCAL CONTEXT IS TAKEN CARE OF FOR THAT PARTICULAR STUDY. IRB EXCHANGE CAPTURES DOCUMENTS THAT ARE IMPORTANT FOR IRB REVIEW, IT'S A COMPLETE SET OF DOCUMENTS. THING LIKE PROTOCOL, FINAL ACTION LETTER BY THE IRB APPROVING THE STUDY, ALL THE CONSENT FORMS, POSTERS, BROCHURES, PATIENT INSTRUCTIONS, DIARIES, THOSE KINDS OF TOOLS ALL PART OF A GIVEN STUDY WERE STORED AND SO THERE'S A SINGLE SITE FOR ANY OF THE HUNDRED OR MORE SITES PARTICIPATING IN A STUDY TO GO TO TO GO TO TO GET THEIR DOCUMENTS, MAKE SURE THEY HAVE THE SAME DOCUMENTS ALL THE OTHER SITES ARE USING. AND THEN IT ALLOWS FOR INVESTIGATIVE TEAMS TO ACCESS DOCUMENTS SO YOU CAN GO INTO THE SYSTEM AND YOU CAN SEE ALL THE SITES THAT HAVE APPROVED THE STUDY, THE DATE THERE, IT MEANS IT'S BEEN APPROVED. NO DATE IT'S NOT APPROVED AT THAT SITE OR RELIANCE HAS BEEN AGREED TO. AND THEN YOU CAN CLICK DOWN ON YOUR UNIVERSITY AND SEE THE DOCUMENTS AND THE OTHER PARTS YOU NEED TO SEE FOR YOUR AREA. COORDINATING CENTER FOR MULTI-SITE STUDY, LOOK AT ALL THE SITES THEY ARE OVERSEEING IN THE STUDY AND GET IMMEDIATE VIEW OF WHAT THE SITUATION IS WITH REGARD TO IRB IN THIS STUDY. AND THEN EXCHANGE ALSO MANAGES COMMUNICATIONS BETWEEN THE SITES. THIS IS AN E-MAIL MESSAGE FROM THE SMART IRB EXCHANGE TO SIDES ENGAGED IN A STUDY AND THEY ARE BEING PROVIDED WITH THESE REVIEWS DOCUMENTS. YOU COULD ALSO GO TO THE EXCHANGE WEBSITE AND SEE THE SAME DOCUMENTS, BUT THEY ARE BEING SENT IN THIS FORMAT SO THE SITES CAN DO WHAT THEY WISH WITH THOSE DOCUMENTS IN THEIR OWN FILING SYSTEM. IT SAYS THE STUDY'S BEEN APPROVED, AND THE NAME OF THE STUDY AND THAT IT HAD EXPIRATION DATE OF MAY 23, 2018, WHO THE CONTACT PEOPLE ARE, WEBSITE INFORMATION. SO THESE ARE AUTOMATED AND OCCUR IN A TIMELY FASHION, ALONG WITH REMINDERS LIKE CONTINUING REVIEWS DUE IN A MONTH, YOU NEED TO DO THAT. AND THIS IS THE ZED STUDY OUT OF THE TRIAL INNOVATION NETWORK, THIS IS SHOWING YOU THE SITES THAT APPROVED THE STUDY, AGAIN DATE MEANS RELIANCE IS COMPLETE, THESE ARE STILL IN PROCESS WHEN THERE'S NO ITEM THERE. AND I DON'T KNOW IN THE ANIMATION IS WORKING ON THIS ONE. AS NEW APPROVALS ARE NEEDED THEY ARE ADDED HERE, RENEWALS AND AMENDMENTS ADDED THERE. THIS IS THE CURRENT 90 SITES THAT SIGNED BOTH THE SMART EXCHANGE -- SMART AGREEMENT AND IRB EXCHANGE AGREEMENT, ONES IN BOLD ARE CTSAs, 41, A LITTLE OVER 60% SIGNED ALL THE DOCUMENTS NECESSARY. HERE YOU CAN SEE TRIAL INNOVATION STUDIES IN THE PIPELINE, 7 STUDIES, WE DON'T KNOW THE NUMBER OF SITES ON THOSE. 18 ALREADY IN THE EXCHANGE, WITH 128 SITES, AND 13 NON-ZEDS STUDIES, THE EXCHANGE WEBSITE IS GENERIC, YOU DON'T HAVE TO BE A TRIAL INNOVATION NETWORK STUDY TO USE THE EXCHANGE. THERE'S 13 MULTI-SITE STUDIES IN THE EXCHANGE WITH 121 SITES IN THOSE STUDIES, TOTAL OF 138, 249 SITES USING THE EXCHANGE TO KEEP TRACK OF WHAT'S GOING ON IN THEIR PROJECTS. I THINK -- SO WE HAVE SOME THINGS THAT WE'RE CONTINUING TO DEVELOP A WEBSITE TO DO A BETTER JOB CAPTURING AND AUTOMATING LOCAL CONTEXT, PROVIDING -- MAKING IT EASY FOR NON-IRB PERSONNEL LIKE SPONSORS AND OTHERS TO GET TO THIS INFORMATION AND SEE IT. AND SOME OTHER THINGS HERE, A BIG ONE TO FACILITATE IRB SUBMISSION INTO THE SYSTEM. RIGHT NOW INVESTGATORS STILL HAVE TO USE THEIR LOCAL IRB SYSTEM TO SUBMIT AND TRY TO AUTOMATE THAT PROCESS BUT WE CAN SEE OUR WAY FORWARD TO DO THOSE THINGS. TO CHRIS' QUESTION, WILL THIS WORK, IT'S ALREADY WORKING, CHRIS. I'M ABSOLUTELY CONFIDENT THAT IF WE CAN STAY ON THIS TRACK THAT WE'LL HAVE A SYSTEM THAT WORKS VERY NICELY FOR PEOPLE AND WE CAN ACTUALLY USE IT TO BUILD OTHER ASPECTS LIKE STANDARDIZED CONTRACTS AND STANDARDIZED CONFIDENTIALITY AGREEMENTS, THAT ARE THE SAME AND MIGHT AS WELL HAVE A SET EVALUATING SUCCESS DOCUMENTS THAT TAKES CARE OF THAT. I THANK YOU, CHRIS, FOR YOUR ENTHUSIASM AND PETRA'S PASSION FOR MAKING THIS ALL WORK AND RADONNA AND MICHELE AND MONICA ENTHUSIASTIC SUPPORT FOR THE PROGRAM AND MADE IT POSSIBLE. CTSA P.I.s ARE COMING ON TO IT NICELY AS WELL. SO I THANK THEM. THANK YOU. >> I BELIEVE LEE NADLER IS NEXT. >> I'M GOING TO TELL A SLIGHTLY DIFFERENT STORY, VERY MUCH WHAT CHRIS SAID, THE HOW AND THE WHY AND WHAT THE DIFFERENCE IT WILL MAKE. AS I WAS LISTENING TO PETRA AND TO MICHELE AND GORDON IT REMINDED ME I'VE BEEN A FUNDED NIH INVESTIGATORS FOR 40 YEARS, I'VE STUDIED HUMANS, PIECES OUT OF THEM, DEVELOPING ANTIBODIES, DOING HUMAN TRIALS. AND THE ONE THING THAT GOT IN MY WAY WAS THE IRB. YOU CAN'T DO ANYTHING WITHOUT THE IRB. THE IRB IS THE SINGLE COMMONALITY OF TRANSLATIONAL SCIENCE. IF YOU'RE REALLY GOING TO DO TRANSLATION, YOU NEED AN IRB. SO WHEN YOU THINK ABOUT WHAT OUR INVESTIGATORS ARE CONCERNED ABOUT, AND WHAT THE NEEDS TO MAKE A DIFFERENCE, TO ACTUALLY CHANGE THE CURVE AND MAKE A DIFFERENCE, THIS IS REALLY IMPORTANT. BARBARA BIERER AND I ARE GOING TO SPLIT THE TALK. I'M GOING TO DO BACKGROUND WORK AND TURN OVER BARBARA TO WHAT WE'RE GOING TO DO. I PUT IN TWO QUOTES, ONE FROM CHRIS AND ONE FROM FRANCIS. THIS IS THE VISION. WHAT CHRIS SAID, I REALLY LIKE THIS, NO DISEASE WAITS FOR IRBs OR OTHER OBSTACLES THAT SLOW CLINICAL RESEARCH, NCATS' MISSION IS TO DEVELOP SOLUTIONS TO THESE KINDS OF SYSTEMIC, PREVIOUSLY INTRACTABLE TRANSLATIONAL SCIENCE PROBLEMS. I WANT TO EMBELLISH. THE WORK WE'RE DOING IS FOR PATIENTS. IT IS ABOUT PATIENTS. THIS IS NOT ABOUT INSTITUTIONS. THIS IS ACTUALLY NOT ABOUT NCATS. THIS IS ABOUT PATIENTS WHO NEED TRIALS AND THEY NEED THESE TRIALS WHEN THEY NEED THEM AND THEY DON'T HAVE SIX MONTHS TO WAIT TO GET IT TO MOVE FROM ONE INSTITUTION TO ANOTHER. AND AS MICHELE DISCUSSED, FRANCIS DECIDED THAT THIS WASN'T -- IT WILL BE A WILL AND BASICALLY SAID WE ARE GOING TO MAKE EVERYONE WORK TOGETHER AND FIGURE OUT A MECHANISM SO THAT WE CAN GO FORWARD. IN ONE SLIDE I'M GOING TO TAKE YOU BACK TO A LOT OF HISTORY AND A LOT OF MEMORIES WHICH ARE A STORY THAT REALLY TALKS ABOUT HOW NCATS IS REALLY GOING TO CHANGE THE CULTURE AND THE NATION. AND I MEAN THAT. WHEN OUR CTSA PRECEDING NCATS WAS FIRST FUNDED, THE SINGLE LARGEST PROBLEM WE HAD AT HARVARD IS WE HAD INDEPENDENT ACADEMIC HEALTH CARE CENTERS. IF YOU WERE AT ONE SIDE, BETH ISRAEL, AND WANTED TO WORK WITH SOMEBODY AT MASS GENERAL, OTHER SIDE OF TOWN, IT TOOK SIX MONTHS TO OPEN THE TRIAL. IT WAS 4 MILES AWAY BUT THEY WOULDN'T BUS THE PATIENT. NOBODY WAS WILLING TO DO EXCHANGES WITH THE PATIENT. WE HAD A PROBLEM AT HARVARD. IF WE WERE GOING TO OPEN TRIALS TO MAKE THEM AVAILABLE TO OUR PATIENTS AND NOW SCIENCE CAME IN THAT SPECIMENS WERE TAKEN OUT AT ONE HOSPITAL AND BROUGHT TO THE NEXT HOSPITAL, AND WE COULD STUDY SOMETHING, WE HAD TO SOLVE A PROBLEM. AND WHEN WE WERE WRITING OUR CTSA APPLICATION, BARBARA BIERER, WHO I HAND ALL THE RECOGNITION HERE, CAME TO ME AND SEED THERE'S AN OPPORTUNITY, THERE HAVE BEEN PEOPLE LIKE KEITH NORRIS AND CHARLES DREW AND OTHERS WAY BEFORE NEURO NEXT AND EVERYTHING ELSE WHO SAID YOU CAN FORM A TREATY BETWEEN INSTITUTIONS AND THAT TREATY IS BUILT ON A RELIANCE AGREEMENT WHICH YOU MUST GO THROUGH LAWYERS AND GOD KNOWS HOW MANY MEETINGS BUT YOU AGREE AND YOU WRITE IT AND YOU PUT IT ON PAPER. ONCE THE TREATY IS WRITTEN, AND YOU'VE ALL SIGNED IT, THEN ALL IT TAKES TO OPEN THAT PROTOCOL IS THE SIGNATURE OF AN INSTITUTIONAL OFFICIAL. OUR DEAN THOUGHT IT WAS NUTS BUT WITHIN -- AS SOON AS WE GOT IT GOING, WITHIN THE FIRST SIX MONTHS HE CAME TO US OVER AND OVER AND AGAIN AND WOULD SAY I HEAR FROM PEOPLE AT OUR HOSPITALS THAT YOU'VE DONE SOMETHING TRANSFORMATIVE. AND WITHIN A YEAR OR YEAR-AND-A-HALF HAD ALL THE HARVARD HOSPITALS SIGNED UP AND GREAT STORIES OF WHAT HAPPENED AT THE MARATHON BOMBINGS, AND WE OPENED SOMETHING CROSSING. IT WASN'T ABOUT HARVARD. IT WAS ABOUT OUR PATIENTS. WHAT WE DID AND I THINK IT'S A LESSON OF NCATS, ONCE WE LEARNED SOMETHING, ONCE WE DEVELOPED AND DEMONSTRATED OUR RESPONSIBILITY WAS TO DISSEMINATE. AND SO IT WAS THE RELIANCE AGREEMENT, IT WAS THE CONCEPT OF HOW TO DO SEED REVIEW THAT WE SHARED, AND THE FOLLOWING SITES BELOW HARVARD CATALYST EACH WITHOUT GIVING US ANY ATTRIBUTION OR NAME OR ANYTHING PICKED UP THE CONCEPT, WORKED ON THEIR OWN RELIANCE AGREEMENTS, TOOK OUR MODEL, CHANGED IT TO THEMSELVES AND THE MOST REMARKABLE WAS THAT THE CHANCELLOR OF THE UNIVERSITY OF CALIFORNIA SAID TO SAN FRANCISCO, L.A., AND SAN DIEGO, IRVINE AND WHAT'S MY LAST ONE? DAVIS. THAT YOU'RE GOING TO WORK TOGETHER. YOU'RE GOING TO WORK TOGETHER. AND THEY WENT FROM INDIVIDUAL INSTITUTIONS TO A NETWORK WHICH REMAINED INTACT. UC BRAID WAS BORN. THIS HAPPENED, WE WALKED INTO THE ROOM WHEN NCATS WAS FORMED WITH CHRIS AND WITH PAMELA AND OTHERS AND WE SAT IN THE ROOM IN THE FIRST STEERING COMMITTEE AND TOLD THEM ABOUT THE SEPARATE ONES. WE SAID THERE'S LOW-HANGING FRUIT HERE. I HAVE TO TAKE MY HAT OFF TO CHRIS BECAUSE HE BASICALLY SAID WE'RE GOING TO DO IT. THEY SAID IT CAN'T BE DONE BUT WE'RE GOING TO DO IT. SO THANK YOU, CHRIS. WITHOUT THAT MOMENT IN TIME, AND WITHOUT YOUR RESOLVE THIS WASN'T GOING TO HAPPEN. SO NCATS THEN WITH PETRA LEADING THIS BASICALLY DECIDED TO STAND UP IRB RELIANT, ALAN GREEN AT DARTMOUTH BAKE BECAME THE LEADER. TO DECIDE IF IT WAS GOING TO BE SHARE, RELIANCE AGREEMENT, GORDON WAS PART OF US, AND TO SEE WHETHER WE COULD GET OUR NETWORKS ALREADY ESTABLISHED TO PUT TOGETHER A SINGLE DOCUMENT TO COME TOGETHER AND SHARE TO BUILD AN INFRASTRUCTURE. THIS WAS TOUGH WORK. THIS WAS REALLY HARD WORK. AND AS THE CONCEPT FOR TICs AND RICs CAME TOGETHER AND NCATS WAS THINKING IT THROUGH IRB RELY HAD NOT MADE THE TRANSFORMATION. IT TOOK ANOTHER YEAR FOR NCATS TO THINK THIS THROUGH, PAMELA HELPED US, AND THE IDEA OF SMART IRB WAS BIRTHED. SO WHAT IS SMART IRB? WELL, WE DIDN'T NAME IT THAT. WE THANK NCATS FOR THAT NAME. BUT IT WAS BASICALLY TO BRING TOGETHER ALL OF THE CTSAs AND AFFILIATED INSTITUTIONS TO COME TOGETHER AND MAKE A TREATY. NOW IF YOU THINK THAT'S EASY, YOU DON'T UNDERSTAND ACADEMIC HEALTH CARE SYSTEMS AND THEIR LAWYERS. AND OUR STATES, RIGHT? EVERY ONE OF THE STATES. UNBELIEVABLE ENOUGH, WITH BARBARA AND MICHELE COB AND SABUNE WINKLER AND THE TEAM, THEY WALKED SITE BY SITE BY SITE, THE ONLY CONTRIBUTION I MADE IS I SCREAMED AT THE P.I.s NIGHT AND DAY. SO SLOWLY BUT SURELY, THAT BEGAN TO HAPPEN. TRUE ANNANTHA? YES, I WAS SCREAMED AT. NO ONE EVER SAID I WAS QUIET. BUT AS GORDON BRILLIANTLY SAID, IT'S NOT A PIECE OF PAPER. IT'S ALL THE STUFF AROUND IT. IT'S HOW YOU BUILD THE SYSTEM SO THAT IT DOESN'T REQUIRE ANYBODY AT THE LOCAL SITE TO DO ANYTHING. SO THE GUIDANCE AND OPERATING PRINCIPLES AND WORK FLOWS WE WORKED WITH NCATS NON-STOP. THEY WERE OUR TEAMMATES. I WANT TO SAY RIGHT NOW, THIS IS THE BEST EXAMPLE OF TEAM SCIENCE I'VE EVER SEEN IN MY LIFE. NCATS WITH THE P.I.s, WITH THE INSTITUTIONAL OFFICIALS, WITH LAWYERS, WITH EVERYBODY, CAME TOGETHER AND EVERYBODY WAS PULLING THE ROPE IN ONE DIRECTION. WE GOT SOPs DONE. TO MAKE THIS WORK, TO GET IT ON THE GROUND, THE IDEA OF BARBARA MICHELE AND SIBOON, PUT A GROUP OF PEOPLE ON THE GROUND THAT WERE LOCAL, REGIONAL, RESPECTED AND TRUSTED, WE CALL THEM AMBASSADORS, AND THEY DROVE IT HOME, LOCALLY AND TAUGHT PEOPLE HOW TO USE IT. BARBARA WILL TALK TO YOU RIGHT AFTERWARDS ABOUT HOW WE ARE TRYING TO HARMONIZE EVERYTHING ELSE FOR MICHELE TRYING TO LEAD THIS, HARMONIZING EVERYTHING WE DO AND THEN OF COURSE WE NEEDED INFORMATIC TOOLS. SO SMART IRB WAS BUILT IN A FEW STEPS, NOW THAT YOU SEE THE BACKGROUND WE HAD PEOPLE, WE HAD TO HAVE A WAY FOR THEM TO JOIN. WE BUILT JOIN THE TOOL, HOW THEY COULD ENABLE AND GET ALL THE DOCUMENTATION AND INFORMATION IN AND KNOW THEY WERE OKAY TO JOIN AND THEN ONCE THEY JOINED HOW DO YOU MAKE EVERYTHING WORK? EVERY ONE OF THE PROBLEMS HAD TO BE SOLVED. THIS WILL NOT BE SOLVED THIS YEAR. THIS WILL NOT BE SOLVED IN FIVE YEARS. BUT THE MORE WE WORK, THE MORE THE CULTURE WILL CHANGE, AND THAT'S WHAT'S REQUIRED. * OH. I DIDN'T WANT THAT, BUT IT'S COMING UP. IT WAS ON THE SLIDE. IF I PUT SOMETHING ON THE SLIDE, IT'S GOING TO TALK, WHETHER YOU LIKE IT OR NOT. * I DON'T KNOW HOW TO STOP IT OR I WOULD. THIS IS ON EVERY CTSA WEBSITE. [ MUSIC ] I CAN PROBABLY STOP AFTER THAT. [ MUSIC ] >> THAT'S UNBELIEVABLE. I HAD NO CLUE THAT WAS GOING TO TURN ON. LET'S GO THROUGH THIS VERY FAST. I DIDN'T KNOW I WAS GOING TO LOSE TWO MINUTES THERE. OKAY. YOU HAVE AN AUTHORIZATION AGREEMENT. YOU HAVE TO DO THAT. YOU HAVE TO BUILD IT. AND MOST OF THE WORK WAS TO GET EVERYBODY IN THE INDIVIDUAL SITES, LAWYERS AND EVERYONE TO SIGN THAT. THEN HAVE EVERYONE UNDERSTAND THEIR ROLES AND RESPONSIBILITIES. AS I TOLD YOU, BRING LOCAL EXPERTISE, AMBASSADORS, INDIVIDUALS AT EVERY CTSA. WE ALL HAVE FUNCTION AT OUR CTSAs, TO DO IRB AND ACCRUAL. FINALLY TO BUILD THE INFORMATICS TOOL. SO TO DATE, 271 INSTITUTIONS HAVE JOINED, MOST IMPORTANTLY, AND IT EVEN SURPRISED ME, WE MADE THE PROMISE THAT BY FEBRUARY 1 WE WOULD SIGN UP THE CTSAs, AND WE SIGNED UP THE CTSAs, AND FOR ME I THOUGHT ON THAT DAY, I WROTE TO CHRIS AND I SAID THE CONSORTIUM IS REAL. CONSORTIUM IS REAL. IT BROUGHT IN NOT ONLY THE CTSAs BUT ALL OF THEIR AFFILIATES, OTHER UNIVERSITIES, ACADEMIC HEALTH, BUT THEN WE WENT TO THE COMMUNITY HOSPITALS, PCORI CAME IN, PCORnet. IT IS A NATIONAL NETWORK. I'M GOING TO SKIP THAT BECAUSE GORDON SHOWED THAT. SO WHAT DOES THIS DO FOR THE INVESTIGATOR, FOR THE NATION? I THINK IT MAKES IT EASY. YOU DO NEED SOMEBODY FOR THE FIRST TIME YOU USE THIS. YOU HAVE TO BE ABLE TO KNOW HOW TO PUT THE DATA IN, WHO YOU'RE GOING TO -- WHO IS GOING TO BE THE REVIEWING IRB, THE RELYING IRB, BUT UNLIKE THE TRIAL INNOVATION NETWORK WHICH IS TRANSFORMATIVE FOR THE NATION, 95 TO 99% OF THE TIME YOU'RE WORKING WITH ANOTHER INSTITUTION. IT'S NOT A LARGE NATIONAL MULTI-SITE TRIAL. IT'S A COUPLE OF INSTITUTIONS THAT THE LAW SAYS WE WORK WITH ONE IRB. AND SO THE SMART IRB RELIANCE TREATY AND INFORMATIC PLATFORM CONNECTS THE NATION ALL INTO ONE. RIGHT NOW THE FIRST DATA IS 342 USERS HAVE REGISTERED, 203 INSTITUTIONS, 94 RELIANCE, 34 COMPLETED ARRANGEMENTS, WE'RE OFF AND RUNNING. BARBARA WILL TELL YOU THE REAL PROBLEM, FOR NCATS STANDING UP HERE THIS IS AN NCATS SUCCESS, IS A TRANSFORMING MOMENT. >> YOU NEVER KNOW WHAT LEE IS GOING TO SAY. LET ME JUST START WITH THE FIRST CORRECTIVE STATEMENT WHICH IS ACTUALLY WHAT HAPPENED IS ALL OF US AT HARVARD WERE GATHERED AROUND SORT OF TEN YEARS AGO THINKING WHAT WE WERE GOING TO PUT TOGETHER FOR THE CATALYST, OUR FIRST APPLICATION. WE HAD PROBABLY 60 PEOPLE IN THE ROOM, EVERYBODY TALKING ABOUT THEIR GREATEST NEEDS. AND SOMEBODY, A PEDIATRICIAN SAID THE THING WE NEED AT HARVARD IS ONE IRB. I WAS AN INSTITUTIONAL OFFICIAL AT THE PROGRAM. I SAID, WELL, THAT WILL NEVER HAPPEN. THAT'S THE TRUTH! [LAUGHTER] SIX MONTHS LATER, I REALIZED, YOU KNOW, THAT'S NOT -- SO FOLLOW ON EIGHT YEARS LATER, WHEN WE'RE STILL WALKING THIS PATH TO ADMINISTRATIVE SIMPLIFICATION AND HAVE OUR NEXT RENEWAL SORT OF EFFORT AND WE'RE SORT OF PLANNING THE RENEWAL THAT WE SUBMITTED, AND WE ALL SORT OF WENT AROUND WITH WHAT ARE OUR NEXT SORT OF MOST STRATEGIC ISSUES, AND ONE OF THE OTHER PROGRAM LEADERS LOOKED AT ME AND SAID WHY DON'T WE SKIP WHAT BARBARA HAS TO SAY, EVERYTHING SHE DOES IS SO BORING. AND THERE IS AN ELEMENT OF TRUTH TO THAT BECAUSE IT'S ALL ADMINISTRATION, IT'S ALL SORT OF GETTING AT THE CORE THINGS THAT MAKE CLINICAL RESEARCH SO DIFFICULT AND SO EXPENSIVE. AND I THINK THAT WHILE THIS IS UNDERAPPRECIATED, THE P.I.s ARE ACTUALLY SPENDING A LOT OF TIME DOING THIS. AND GETTING OVER THAT HUMP GIVES THEM MORE TIME FOR RESEARCH, OR TO WRITE GRANTS OR WHATEVER ELSE THEY HAVE TO DO. BUT IT WAS CLEARLY ONE OF THE THINGS THAT THE NATIONAL ACADEMY OF SCIENCES CALLED FOR ON THEIR RESEARCH REGULATIONS FOR THE 21ST CENTURY. SO, YOU KNOW, WE THINK WE'VE DONE A SIGNIFICANT AMOUNT OF WORK TO GET THERE. WE'VE ALSO, AS WE SAY, PASSED THE TIPPING POINT. NOW WHEN WE GO TO AN INSTITUTION AND SAY WE HAVE A RELIANCE, THEY SAY WE'LL SEND IT TO OUR LAWYERS, GO AHEAD, 271 INSTITUTIONS SIGNED IT, THEY SAY WE'LL SIGNED IT. IF YOU GET OVER THE ISSUES AT HARVARD, YOU CAN SORT OF SIGN ANYTHING. SO THAT'S BEEN REALLY VERY HELPFUL. THE OTHER THING I'LL SAY IS THAT WHILE IT SAVES TIME FOR THE INVESTIGATORS, AS GORDON SAID AS LEE IMPLIED BY THE TIME YOU'RE OPERATIONALIZING A STUDY, AND THE STUDY COORDINATORS ARE WORKING ON THREE DIFFERENT STUDIES, ONE REVIEWED BY INSTITUTION A, ONE BY B AND ONE BY C, EVERYBODY HAS A DIFFERENT PROCESS AND EVERYBODY HAS A DIFFERENT -- SLIGHTLY DIFFERENT WAY OF APPROACHING THINGS BUT YOU'LL BE OUT OF COMPLIANCE IF YOU DO IT IN A'S WAY FOR A B STUDY. SO THE PEOPLE THAT ARE ON THE SHARP, YOU KNOW, SHARP EDGE OF THE KNIFE IN TERMS OF COMPLIANCE ARE THE PEOPLE WHO ARE REALLY ON THE FRONT LINE TRYING TO DO THE RIGHT THING AND IN SO FAR AS ALL OF OUR POLICIES ARE DIFFERENT, AND IN TRIVIAL WAYS, TWO EXAMPLES. WHAT IS THE AGE OF ASSENT, HOW OLD DOES SOMEBODY NEED TO BE? WITHIN HARVARD INSTITUTIONS IT'S EITHER 12 OR 13. SO THEY FEEL VERY STRONGLY THAT A CHILD CAN ASSENT AT 12, AND ANOTHER INSTITUTION FEELS VERY STRONGLY IT'S 13. I'M LIKE, JUST CHOOSE ONE. YOU KNOW, AND THEN SAY, IF YOU CHOOSE 13, BECAUSE PEOPLE FEEL VERY STRONGLY ABOUT THAT, THEN SAY BUT IN THE OPINION OF THE, YOU KNOW, INVESTIGATOR IF SOMEBODY -- IF A CHILD IS OF PARTICULAR INTEREST AND CAPACITY, THEY SHOULD ASSENT TO THE TRIAL AND GIVE THEM FLEXIBILITY EVEN TO ASSENT AN 11-YEAR-OLD. WE CAN'T GET THERE YET. PART OF IT IS STATE REGS, PART IS SORT OF INSTITUTIONAL POLICY. BUT IF WE DON'T FIGURE OUT HOW TO DO THIS, THIS BATTLE WILL GO ON BUT IT WILL GO ON NOT AT THE RELIANCE BUT AT THE OPERATIONS. SO IN APPRECIATING THAT, WE WENT AHEAD AND HAVE FIRST OF ALL ESTABLISHED A SIGNIFICANT EDUCATION RESOURCE SORT OF TOOLBOX FOR PEOPLE, CHECK LIST AND WEBINARS AND RECORDED THE WEBINARS AND PUT THEM UP AND REALLY A LOT OF DISSEMINATION TOOLS WHICH MICHELE COBB MASTERED, AND IT DOES HELP WITH IMPLEMENTATION. I SHOULD SAY WHILE WE'RE ALL STANDING AROUND HERE, QUITE FAMILIAR WITH THIS SPACE, A LOT OF INSTITUTIONS DON'T KNOW HOW TO DO THIS. AND IN FACT OUR PILOT, BELIEVE IT OR NOT, WAS DUKE. AND DUKE HAD NOT DONE A RELIANCE AGREEMENT WHEN WE WERE DOING IRB RELY. I MEAN NOW DUKE IS WELL ENGAGED IN THIS BUT FOUR YEARS AGO, FOUR YEARS AGO, MAJOR INSTITUTION WAS NOT. DUKE CRI DID NOT HAVE A RELATIONSHIP WITH DUKE MEDICAL CENTER. THAT'S HOW DISCONNECTED WE ARE. SO WE'RE BRINGING THAT TOGETHER. WE ALSO HAVE A WHOLE SET OF SORT OF FAQs AND CHECK LISTS AND TOOLS AND SORT OF HOW-TOs AND WHO YOU CALL AND WHAT'S THE ROAD MAP FOR LOTS OF -- DEPENDING ON YOUR FUNCTION AND YOUR ROLE. AGAIN, THIS IS WHAT WE THINK AT SMART IRB WE SHOULD BE DOING BUT THERE'S NO CONSISTENCY ACROSS THE NATION AND EVEN AT THE NIH NEURO NEXT IS SLIGHTLY DIFFERENT THAN STROKE MET, BOTH FUNDED BY NINDS, BUT SLIGHTLY DIFFERENT. AND NCI, CIRB, DIFFERENT THAN NEURO NEXT. AND WE NEED TO PULL ALL OF NIH INTO ONE WAY OF DOING BUSINESS, AND IT WILL MAKE IT EASIER FOR EVERYBODY. THE REAL CHALLENGE THOUGH IS THEN BEYOND THE NIH INSTITUTIONS WHAT DO WE DO ABOUT V.A., WHAT DO WE DO ABOUT THE DoD, WHAT DO WE DO ABOUT ALL OF THESE OTHER GROUPS AND FEDERAL AGENCIES THAT HAVE DIFFERENT REGULATIONS AND HAVE THEM EITHER BASED IN THE LAW OR BASED IN CULTURE. SO WE'RE ACTUALLY STARTING TO ATTACK THIS. THIS IS NOT GOING TO BE -- ATTACK IS A STRONG WORD BUT WE'RE GETTING THE FOLKS TOGETHER TO DISCUSS THIS. IT'S NOT GOING TO BE EASY. YOU KNOW, THERE'S A RULE FOR INSTANCE THAT A V.A. REPRESENTATIVE OF THE STUDY MUST SIT ON THE IRB WHO IS REVIEWING THE STUDY FOR THAT INSTITUTION. IF YOU REVIEW AT A DISTANCE, YOU CAN'T DO THAT. SO WE HAVE TO FIND A WAY, UNDERSTAND WHY THE V.A. SEES THAT, UNDERSTAND WHAT THE DOCUMENTATION HAS TO BE FOR PROTECTION OF VETERANS, ET CETERA, IN ORDER TO MOVE FORWARD WITH A HARMONIZED SET. AND MICHELLE AND I HAVE BEEN CO-LEADING WHAT WE CALL A HARMONIZATION STEERING COMMITTEE. WHILE THE CTSAs ARE STARTING TO REALIZE THEY CAN'T FIGHT BACK ANYMORE BASICALLY, THAT'S NOT TRUE BEYOND NCATS AND THE NCATS INSTITUTIONS. SO WE PUT TOGETHER HARMONIZATION STEERING COMMITTEE WITH THE EXPRESS VISION TO PULL THROUGH THESE PROCESSES, POLICIES AND APPROACHES TO THE KIND OF WORK WE DO. AND IN THAT WE MADE SURE WE HAD REPRESENTATIVES FROM OUTSIDE NCATS THAT WOULD BE THEN THE GROUPS THAT REALLY PULLED THEIR COMMUNITIES TOGETHER. AND WHAT WE DID FIRST, THIS IS THE COMMITTEE, IS TO INDEX AND SURVEY EVERYONE ON THE COMMITTEE AS WELL AS THE AMBASSADORS AS TO WHAT THINGS THEY THOUGHT NEEDED TO BE HARMONIZED AND WHAT WAS BOTH TRACTABLE, IT COULD BE CHANGED, I CAN'T YOU CAN'T CHANGE STATE LAWS BUT YOU CAN CHANGE CERTAIN POLICIES, WHAT IS THE INTERVAL BY WHICH YOU HAVE TO REPORT ADVERSE EVENT, SERIOUS ADVERSE EVENT. DO YOU REPORT TO THE P.I. OR TO THE IRB? OR BOTH? THOSE ARE THE KINDS OF TRIVIAL, AS MY FRIEND SAYS BORING, THINGS THAT NEED TO GET SORTED OUT, AND WE PULLED IN INDIVIDUALS THAT REALLY HAD ENORMOUS EXPERIENCE I RUNNING THIS AND FOR GOOD REASON HAD COME UP WITH THEIR APPROACH TO DOING THIS. IT'S BEEN A VERY DEDICATED GROUP, MEETING ONCE A MONTH, AND WE SURVEYED EVERYONE AND THEN ASKED THEM TO PRIORITIZE THE ISSUES THAT CAME UP. AND THEN WE STARTED BY SPLITTING INTO FIVE SUBCOMMITTEES WHERE EACH SUBCOMMITTEE -- THERE'S A MEMBER OF THE OVERALL STEERING COMMITTEE AND ADDITIONAL WORKER BEES WHO KNOW THE CORE CONTEXT. AND THERE ARE THINGS LIKE INSTITUTIONAL VERSUS LOCAL AND STATE REQUIREMENTS. WHAT IS A POLICY, WHAT IS REQUIRED AT THE STATE LEVEL? INSTITUTION-- WHAT IS THE INSTITUTIONAL RESPONSIBILITY VERSUS IRB RESPONSIBILITY? NOW, YOU MIGHT KNOW THAT OHRP, THE OFFICE OF HUMAN RESEARCH PROTECTIONS, PUT OUT A REQUEST FOR INFORMATION, I THINK IN 2009, SAYING, YOU KNOW, FOUR SINGLE SITE REVIEW OF MULTI-SITE TRIALS WHAT SHOULD BE THE INSTITUTIONAL VERSUS IRB RESPONSIBILITIES BECAUSE IN THE REGULATIONS WHO DOES THIS IS FLEXIBLE. YOU CAN HAVE FLEXIBLE RESPONSIBILITIES IF THEY ARE GOING TO BE NATIONALLY ADOPTED -- YOU CAN'T HAVE FLEXIBLE RESPONSIBILITIES IF THEY ARE GOING TO BE NATIONALLY ADOPTED. I'M GOOD FRIENDS WITH OHRP AND CALLED THEM. WHAT DID YOU FIND? THEY SAID WHY DIDN'T YOU EVER ISSUE ANYTHING ABOUT THIS? IT WAS VERY INTERESTING, AND WE'RE ALL OVER THE MAP. I REALIZED WE HAVE A LOT OF WORK TO DO. I MEAN, A LOT OF WORK TO DO. THEM HAVE DELIVERABLES, HAVE A REAL TOOL AT THE END OF IT THAT WILL COME OUT THE PLAN IS HERE TO DEVELOP RESOURCES IN THE SUBCOMMITTEES, AGREEING IN CONTENT, PROCESS AND POLICY TO BRING RESOURCES BACK TO THE HSC, HARMONIZATION STARING COMMITTEE, LET THEM INTERNALLY REVIEWED AND PROVIDE FEEDBACK AND GO TO THEIR COMMUNITIES AND FIGURE OUT WHETHER THIS WORKS FOR THEM. I.E., YOU KNOW, THE V.A. CAN GO GET THE OTHER EXPERTS AT THE V.A. TO SEE IF THIS WOULD WORK OR NOT. THE DoD CAN TELL US IF THAT WOULD WORK OR NOT BECAUSE THEY KNOW THEIR REGULATIONS. AND THEN ONCE WE FINALIZE IT, GIVE IT TO THE TRIAL INVASION NETWORK, THE TENs, AS A PROTOTYPE, SORT OF PROCESS OR POLICY, AND LET THEM BE THE EXPERIMENTAL TEST ENGINE TO SORT OF OPERATALLIZE SOME OF THIS AND SEE WHETHER IT WORKS OR DOESN'T. IF IT DOESN'T WE WILL ITERATE UNTIL IT'S RIGHT, POST FOR PUBLIC COMMENT FOR 30 OR 60 DAYS AND DISSEMINATE. WE DON'T HAVE AUTHORITY EXCEPT TO DO THE RIGHT THING AND GET 272 INSTITUTIONS AND MORE TOMORROW TO DO IT THE WAY WE'RE DOING IT AND THERE IS A CERTAIN POWER OF PERSUASION. I'LL MAKE A COUPLE OTHER POINTS. ONE IS THAT IT IS CRITICALLY IMPORTANT AS WE MOVE FORWARD TO HAVE ONE I.T. INFRASTRUCTURE TO SUPPORT THE WORK FLOW SO INDIVIDUALS ARE NOT SPENDING TIME FIGURING OUT WHO THE IRB LIAISON OR POINT OF CONTACT IS AT THE INSTITUTION, THEY ARE NOT WAITING THINKING SOMEBODY IS DOING IT WHEN THEY HAVE TO SIGN OFF ON SOMETHING. WE NEED TO BUILD AN INFRASTRUCTURE TO SUPPORT THIS WORK. IT WILL TAKE RESOURCES AND IT WILL TAKE, YOU KNOW, A COMMUNITY OF PEOPLE. YOU KNOW, WE'RE BUILDING THE ONLINE ALLIANCE SYSTEM WHICH IS DIFFERENT FROM EXCHANGE SYSTEM SO WE'VE GOT A LITTLE BIT OF WORK TO DO IN THAT WAY TO FIGURE OUT HOW THEY INTERDIGITATE, OPEN SOURCE, WE'VE SEEN UPTAKE AND ENTHUSIASM FOR BUILDING IT. BUT WE CAN'T BUILD A WORK FLOW SYSTEM UNTIL PROCESSES ARE LAID OUT AND KNOWN. SO THAT'S OUR CURRENT EFFORT. THE OTHER THING I'LL SAY IS THAT WE'RE ENTHUSIASTIC ALTHOUGH THIS IS A LITTLE BIT OF OUTSIDE THE SCOPE OF OUR CURRENT SUPPLEMENT TO BRING THIS FORWARD TO GET INDUSTRY TO SIGN ON TO THIS WHICH WILL SPEED INDUSTRY SPONSORED PROJECTS TO GET MOM AND MOP SHOPS, COMMUNITY HOSPITALS TO SIGN ON AND DO PHASE 4 STUDIES EASILY AND REALLY START TO MAKE THIS SORT OF THE WAY WE DO THE BUSINESS LIKE SO THAT WE ALL LEARN ONE THING AND WE ONLY HAVE TO LEARN ONE THING. SO-- MEANWHILE OF COURSE THE COMMON RULE CHANGES SO WE'RE GOING TO REDO IT FOR NEXT YEAR. SO BUT, YOU KNOW, WE'VE SEEN ENORMOUS ENGAGEMENT, EDUCATION AND SUPPORT. IT'S A VERY USER FRIENDLY AND INTUITIVE ONLINE RELIANCE PLATFORM. WE HAD A PLATFORM AT HARVARD THAT WE USED. WE SUN SETTED IT AND PEOPLE ARE DELIGHTED THAT WE DID BECAUSE THIS IS SO MUCH BETTER AND EASIER. WE'RE LOOKING FORWARD TO A DAY WHEN THERE'S UNIFORMITY OF POLICY AND PROCESSES AND I HOPE TO SEE INCREASED COMPLIANCE WITH LOWER ADMINISTRATIVE BURDEN FOR ALL. SO WITH THAT, HAPPY TO -- ALL OF US ARE HAPPY TO -- >> THANK YOU VERY MUCH. >> WHILE THEY ARE GETTING GOING I WANT TO SAY A COUPLE THINGS. I WANT TO REITERATE THINGS I SAID THIS MORNING WHEN LEE AND BARBARA WEREN'T HERE. I REALLY AM SO VERY, VERY PLEASED THAT WE ARE AT THIS POINT. I SAID THIS MORNING AND I'LL SAY IT AGAIN I VIEW THIS AS THE MOST IMPORTANT THING NCATS HAS DONE SINCE I BECAME DIRECTOR. AND I REMEMBER VERY WELL THAT FIRST STEERING COMMITTEE MEETING WHEN WE DECIDED TO DO THIS, AND THE FACT THAT WE'RE SITTING HERE LESS THAN FIVE YEARS LATER HAVING DONE IT, IT IS TRULY A DREAM COME TRUE REALLY. IN THE LITERAL SENSE OF THE WORD. AND I'M SO VERY GRATEFUL TO ALL OF YOU FOR DOING THIS. AND SOMETHING I HAVE TO POINT OUT, I WAS STRUCK BY THIS IN ALL YOUR PRESENTATIONS, IS THAT THIS IS ATYPICAL FOR WHAT HAPPENS IN ACADEMIC SETTINGS OR ANY SOCIAL CONSTRUCT, HUMAN CONSTRUCT, AT LEAST THAT TENDS TO FOCUS ON TWO WORDS THAT BARBARA USED THAT THIS GROUP DOES NOT HAVE, POWER AND AUTHORITY. UNFORTUNATELY, HUMAN ORGANIZATIONS ARE ALL ABOUT POWER AND AUTHORITY. THIS ACTIVITY WILL NOT GET PEOPLE TENURE NOT THAT THEY NEED IT BUT THE POINT IS THESE KINDS OF BORING THINGS ARE THE VERY THINGS THAT ARE PREVENTING TREATMENTS FROM GETTING TO PATIENTS. AND THAT HAS BEEN SO CLEAR TO THIS TEAM FROM THE VERY BEGINNING, AND LEE SAID IT AT THE BEGINNING. THAT'S WHY THIS HAS WORKED. BUT IT HAS BEEN ONE OF THE WONDERFUL THINGS TO WATCH, THE SELFLESSNESS WITH THIS WHICH TEAM WORKED. I THINK THAT'S WHY IT'S BEEN SO INSPIRING FOR EVERYBODY, TO SEE THAT. I WANT TO REINFORCE WHAT'S BEEN SAID ALREADY, THAT I REAL DO THING THIS IS GOING TO BE -- IT'S ALREADY TRANSFORMATIVE BUT BEYOND THIS, AS I REFLECTED TO YOU, THE FACT WE DID THIS TOGETHER, AN INCREDIBLE TEAM EFFORT, HAS GIVEN US CONFIDENCE AS A TEAM ABOUT OTHER THINGS WE CAN DO, WHICH I DON'T THINK WE KNOW THE LIMITS OF THAT YET. SO THANK YOU. THE LAST THING I'LL MENTION, WE HAVE IN THIS GROUP, NEITHER IS HERE TODAY, REPRESENTATIVES ON THE BOARD FROM THE V.A., RACHEL RAMONI WHO USED TO BE AT HARVARD, NOW HEAD OF RESEARCH, RELEVANT PART OF RESEARCH AT THE V.A., I WAS AT A MEETING YESTERDAY WITH LARRY MEYER WHO RUNS A LOT OF THIS AS WELL. AND TERRY RAUSCH IS ALSO IN THIS GROUP FROM DoD. SO WE HAVE OFFICIAL MEMBERS OF THIS GROUP WHO I THINK WILL BE REALLY -- AND SO WE'RE EAGER -- YOU KNOW MICHELE ALREADY, BUT ANYTHING WE CAN DO, WE MET WITH THEM A COUPLE TIMES ALREADY BUT ANYTHING WE CAN DO TO EXTEND THIS TO V.A. OR DoD, WE USE ANALOGY, LEE AT LEAST IS A CANCER DOC, WE WANT TO BE LOCALLY INVASIVE AND METASTATIC IN THIS CASE. SO-- (INAUDIBLE) OKAY. SO WITH THAT I HOPE THERE ARE A LOT OF QUESTIONS AND COMMENTS. LET'S GO ERIC AND THEN HARRY AND THEN MEGAN AND THEN LYNN AND THEN DAN AND THEN FRANK >> WELL, IT'S TERRIFIC OF COURSE. I THINK AS WAS ALREADY POINTED OUT BY MANY WHO WOULD HAVE EVER THOUGHT THIS WAS POSSIBLE. I WANTED TO GET INTO THE WORD YOU GOT TOUCHED ON, METASTATIC. AND THAT IS UNFORTUNATELY I THINK WHAT YOU'VE ACHIEVED, WHAT'S HAPPENED HERE, IS BASED ON AN OLD MODEL OF PEOPLE GOING TO SOME PLACE, PHYSICALLY, AND GETTING CONSENT. IT DOESN'T HIT THE PUBLIC. IT'S A VERY NICE STORY BUT THE REAL STORY IS MUCH BIGGER. AND SO WHAT I'M TRYING TO UNDERSTAND HOW CAN YOU TAKE THIS FOUNDATION WHICH IS EXTRAORDINARY ACKNOWLEDGE THEN BUILD IT OUT TO DIGITAL END TO END TRIALS WHERE HAVE YOU MASSIVE INFORMATION RESOURCES TO FIND THE PEOPLE WITH WHATEVER RARE DISEASES OR THEY FIND, CONGESTION SENT, BIOMETRIC, FACE OR THUMB PRINT OR WHATEVER, EVERYTHING GETS BACK, A WHOLE WORLD YOU DIDN'T TOUCH ON YET CAN WE USE WHAT YOU BUILT TO GO TO THE NEXT LEVEL? I'LL TAKE A SHOT FIRST. I LOVE YOUR VISION. EVERYTHING THE TEAM WAS ABLE TO DO WAS BILLETS ON BUILT ON BUILDING RESPECT AND TRUST, IT TAKES A WHILE TO BUILD RESPECT AND TRUST WHERE PEOPLE WILL WORK TOGETHER. AND SO WE NEED TO BALANCE THAT WE SHOW THAT WE CAN DO IT, THAT IT'S STABILIZED, AND ACTUALLY THOUGHTFULLY MOVE TO THE NEXT STEP. WE NEED TO EXPLAIN TO MULTIPLE TYPES OF POPULATIONS, PATIENTS ARE AFRAID. THEY ARE SO USED TO COMING TO THAT DOCTOR AND BUILDING THE TRUST WITH THAT DOCTOR, AND MY DOCTORS, YOU KNOW, THE TROUBLE WE HAVE NOW WITH CONSENTS, GOING TO PRIMARY CARE DOCTOR, DID MY DOCTOR OKAY FOR YOU TO ASK? SO, ERIC, IT'S A LEAP. WE NEED TO GO THERE BECAUSE ACCRUAL TO CLINICAL TRIALS WHICH WE'RE DEEPLY WORKING ON REQUIRE REACHING THE PATIENT, THE FAMILY, AND GETTING IT THERE. LET'S FINISH THIS FIRST STEP. I THINK TODAY IS KIND OF ONE OF THE MAJOR TADAMS OF FINISHING. ERIC, WE HAVE TO ARTICULATE WHAT THE FIRST WOULD LOOK LIKE SO I SUGGEST IT GOES ON CHRIS' NEXT STEERING WHEAT COMMITTEE MEETING. >> WE HAVE ELECTRONIC CONSENT, WE CAN SEND A MESSAGE TO YOUR CELL PHONE, CAN YOU SIGN, THAT'S ALREADY IN PLACE. THEY ARE DISSEMINATING THAT TOOL NOW. >> I WOULD ANSWER DIFFERENTLY. WHAT WE'VE DONE IS FULLY COMPLIANT WITH THE FEDERAL REGULATIONS. REGARDLESS OF WHAT KIND OF RESEARCH YOU'RE DOING, WHETHER IT'S MINIMAL RISK OR FULL BOARD REVIEW. YOU'RE GOING TO NEED THAT AND YOU'RE GOING TO NEED TO BE ABLE TO DOCUMENT IT. I THINK THAT WE HAVE A LOT -- A LONG WAY TO GO IN TERMS OF CONSENT AND IN TERMS OF PEOPLE EMPOWERMENT. SO THEY CONTROL WHAT THEY ARE OFFERED AND THAT IS AS WE ALL AGREE THE NEXT SORT OF UNIVERSAL THING TO TACKLE. >> SHARON HAS A BRIEF COMMENT BEFORE WE GO TO -- >> YEAH, ACTUALLY GREAT QUESTION, ERIC. WE'VE BEEN ENJOYING AS PCORnet WITH THESE FOLKS AND PEOPLE-POWERED RESEARCH NETWORK, 88 SIGNED ON, DIGITAL COMMUNITIES WHERE PEOPLE CONTROL THEIR OWN INFORMATION SO WE HAVE A TOTAL OF 200 PCORnet GROUPS IN THERE BUT 88 ARE PATIENT ARE COMPLETELY COMPLIANT WITH THIS SYSTEM. WE'RE REALLY PROUD OF THAT BECAUSE IT WAS A REALLY DIFFERENT -- AND WE BUILT A TOOLKIT TO BRING DIGITAL COMMUNITIES ON AS A RESULT OF THAT. >> HARRY? >> I WON'T WASTE MORE TIME THANKING YOU FOR YOUR SERVICE BUT IT WAS REMARKABLE. THOSE OF OF YOU NOT NECK DEEP IN CTSAs NOT REALIZE THEY HAVE VERY LITTLE LINE AUTHORITY ON CAMPUS. YEAH, ZERO. FOR THAT TO HAPPEN TAKES ALL SORTS OF PERSUASION, ALL THE THINGS MENTIONED HERE HAD TO COME INTO PLAY, COLLABORATION BETWEEN NCATS, HARVARD, VANDERBILT AND MANY OTHERS. I HAVE TWO TECHNICAL QUESTIONS WHICH ARE AT THE EDGE OF WHAT YOU'RE TALKING ABOUT TRYING TO ELIMINATE BARRIERS. ONE, BARBARA, YOU BROUGHT UP WHICH IS THE INSTITUTIONAL VERSUS IRB RESPONSIBILITY FOR FEASIBILITY, SCIENTIFIC FEASIBILITY, IF YOU WILL, BECAUSE SOME GETS THROWN OVER THE FENCE AT THE IRB, OTHERS GO TO THE INSTITUTION WHERE THEY SAY CAN WE REALLY MOUNT THAT TRIAL PROPERLY? THE OTHER PART HAS TO DO WITH THAT IN THE CONTEXT OF ETHIC, EXCEPTION TO INFORMED CONSENT, BECAUSE THAT HAS TO BE LOCAL IN THE COMMUNITY BUT YOU WANT TO HAVE IT CENTRAL. COULD YOU HELP US UNDERSTAND HOW THOSE KINDS OF THINGS ARE ADDRESSED IN THE SYSTEM? >> YEAH. SO THE EMERGENCY CONSENT, WE HAVE NOT REALLY WALKED THROUGH AND DONE A SUFFICIENT JOB. I DO THINK THAT WE'RE GOING TO NEED TO WORK WITH OHRP TO WORK ON THAT AND DoD WHO ALSO HAVE REGULATIONS ON THAT. BECAUSE YOU DO NEED COMMUNITY PROCESS IN ORDER TO CREATE THE, YOU KNOW, SORT OF THE APPROVAL, AND HOW WE INTERPRET COMMUNITY IS GOING TO BE REALLY COMPLICATED. SO WE NEED TO WORK ON THAT AND GET A MODEL. THIS IS VERY GOOD FOR THINGS LIKE EXPANDED ACCESS, YOU CAN GET ONE IRB TO APPROVE EXPANDED ACCESS AND INFORMED CONSENT AND EVERY OTHER INSTITUTION COULD OR EVERY OTHER INVESTIGATOR COULD RELY ON THAT IRB. SORT OF AN UNDERAPPRECIATED. WHAT WAS THE OTHER THING? >> YOU POINTED OUT ABOUT THE INSTITUTIONAL RESPONSIBILITY, WE'RE WORKING ON SCIENTIFIC REVIEWS COMMITTEES WE FIND SOME PLACES THEY CONSIDER SCIENTIFIC FEASIBILITY TO INCLUDE ABILITY TO RECRUIT BECAUSE OTHERWISE FUTILITY ENSUES, THAT'S THE IRB. OTHERS THROW IT OVER THE FENCE TO THE INSTITUTION. >> THAT'S A REALLY TERRIFIC POINT. I THINK IN GENERAL WE HAVE A LOT OF WORK TO DO ON WHAT WE EXPECT FROM AND IN THE PROTOCOL AND WHAT SHOULD BE PRE-WORKED. WE NEVER SEE THIS PROBLEM, YOU KNOW, FROM INDUSTRY BECAUSE THEY REALLY TAKE IT VERY SERIOUSLY. WE DO A VERY BAD JOB OF FEASIBILITY ASSESSMENT ITSELF. WE LIE AND LIE TO OURSELVES ALL THE TIME. AND YOU SEE THAT AS ANOTHER THICAL ISSUE AT THE END OF SORT OF THE TRIAL WITH EARLY TERMINATION OF TRIALS FOR LOW ACCRUAL, ALSO AN ETHICAL PROBLEM BECAUSE NO RISK IS WORTHWHILE BECAUSE THERE'S BEEN NO GENERALIZABLE KNOWLEDGE AS BENEFIT. SO I SEE THAT VERY MUCH IN SOMETHING I MEAN PERSONALLY THAT THE P.I. IS RESPONSIBLE FOR, THE P.I. SHOULD DOCUMENT HOW THEY ARE GOING TO DO IT, THE IRB SHOULD REVIEW IT. AND I'VE TALKED TO, YOU KNOW, DEB ZARON AND SHE'S DONE A STUDY OF ALL THE DIABETES TRIALS IN BOSTON, AND THEY CAN'T GET DONE, WHICH SHOULD INDICATE THAT WE SHOULD BE DOING MULTI-SITE TRIALS FROM THE GET-GO OR WE SHOULD BE FIGURING OUT HOW TO PRIORITIZE THEM OR WE SHOULD BE FIGURING OUT OTHER WAYS OF MAKING SURE THAT WHEN WE START A TRIAL WE'RE GOING TO COMPLETE IT. SO-- >> I DON'T WANT TO BELABOR THIS, BUT IF YOU HAVE A CENTRAL IRB PROCESS AND IT GOES TO THE INSTITUTION, INSTITUTIONS ARE NOT ACTING RESPONSIBLY WITH REGARD TO PROJECTIOS OF NUMBERS OF PATIENTS TO BE ACCRUED AND SO FORTH AND DO IT BECAUSE OF INCENTIVES, AND YOU CAN IMAGINE WHAT THEY ARE, SOON WHAT YOU HAVE ARE FUTILE TRIALS AND THAT'S UNETHICAL. YET WE'RE INCLUDING PEOPLE IN THOSE TRIALS. I THINK YOU'RE ON TO SOMETHING THAT REALLY NEEDS TO BE -- >> CANCER CENTERS HAVE PROVEN THAT'S TRUE. THEY PROMISE AND THEY NEVER DELIVER. >> NEVER IS A STRONG WORD. >> I THINK AS YOU SAID OTHER PROBLEMS, WITH OUR INCREASING ABILITY TO LINK SOME OF THE FEDERATED ELECTRONIC HEALTH RECORDS, RESEARCH DATA WAREHOUSES AND HAVE EVIDENCE-BASED RECRUITMENT PROJECTIONS AND GATHER THAT INFORMATION, BECAUSE THAT'S WHAT INDUSTRY DOES. THEY HAVE DATABASES AND THE BEST EVIDENCE OF FUTURE PERFORMANCE IS PAST PERFORMANCE, WE'RE STARTING TO TACKLE THAT PROBLEM. IT'S A HARD ONE BUT WE'RE ON THE WAY AS WELL. >> I THINK I'M SPEAKING TO NCATS, IT REALLY WAS THE CTSA P.I.s. EVERY SINGLE INDIVIDUAL P.I. DECIDED THAT THIS WAS THE RIGHT THING TO DO AND HAD TO WORK THEIR INSTITUTION TO GET IT DONE. AND THEY DIDN'T WANT TO SEE IT, LET ME TELL YOU. AND ONE AFTER ANOTHER AFTER ANOTHER, JUST BASICALLY BROUGHT IT HOME. AND SO, YOU KNOW, TO ME THAT WAS A HUGE TRIUMPH. THAT'S WHY I SAID WHEN THAT WAS COMPLETED, THE CONSORTIUM WAS REAL. >> MEGAN? >> FIRST, AS SOMEONE WHO HAD TO WAKE FOR A CLINIC TO OPEN BECAUSE OTHER SITES HAD NOT FINISHED THEIR IRB AND I WAS FRUSTRATED, AS A PARENT OF A SICK CHILD, THOUGHT IT WAS BOLOGNA. I'M VERY APPRECIATIVE, AS A CONSUMER OF THIS, AS A MEMBER OF PCORnet, AS SHARON POINTED OUT, THIS PROCESS WAS MADE INCREDIBLY CLEAR, INCREDIBLY EASY, PAINLESS FOR US TO GO THROUGH AND I THINK THE ONLY REASON PEOPLE DIDN'T SIGN ON FASTER IS PROBABLY JUST IT GOT LOST IN THEIR E-MAIL. YOU KNOW, ON OUR END THERE WAS NO COMPLAINT. THIS MAY HAVE ALREADY BEEN ADDRESSED BUT IS THIS GOING TO BE MANDATORY FOR NIH STUDIES AND SPECIFICALLY RDCRN? WHICH MAY OR MAY NOT HAVE BEEN WHERE I HAD TO WAIT? >> ANYBODY UNDER THE TABLE WANT TO ANSWER THAT QUESTION? >> YEAH, I CAN START IF YOU WOULD LIKE. OF COURSE, BEING AN IRB POLICY AS YOU HEARD MANDATORY FOR NIH-FUNDED STUDIES COMING IN ON OR AFTER JANUARY 25th, WE OF COURSE AT NCATS HAVE ALREADY STARTED WORKING WITH THE RDCRN TEAMS TO HARMONIZE IN OUR OWN CENTER, AND WE ARE WORKING BY INFLUENCING THROUGH, YOU KNOW, OUR CONNECTIONS WITH THE DIRECTOR AND OTHERS TO GET SOME DEGREE OF HARMONIZATION. IT'S A VERY GOOD QUESTION. I THINK IT'S ONE OF THE THINGS THAT FROM THE NIH PERSPECTIVE I GUESS I'D LOVE TO HEAR DISCUSSION ONCE WE'VE MADE ROUND OF COUNCIL QUESTIONS BECAUSE ONE OF THE KEY QUESTIONS IS OF COURSE HOW WILL THIS ECOSYSTEM LOOK LIKE AND BE SCALABLE? AND I THINK THAT'S SOMETHING THAT WOULD BE REALLY INTERESTING TO HEAR PEOPLE -- DOES EVERYBODY HAVE THE SAME, FLEXIBLE AND SCALABLE ENOUGH OR WHETHER THERE'S SOME PLATFORM AND MULTIPLE SOLUTIONS TAILORED TO THE RISK OR THE SCOPES, WE'LL HAVE TO DISCUSS THAT A LITTLE BIT MORE I THINK. >> JUST WHAT THE ART OF THE POSSIBLE, TO START A STUDY YOU NEED IRB APPROVAL AND CONTRACT. YOU JUST CAN'T DO IT, HAVE TO HAVE BOTH. BOTH ARE REQUIRED. SO IN A RARE DISEASE CONDITION, PATIENT POPS UP IN LITTLE ROCK, ARKANSAS, HOW DO YOU BRING THAT SITE UP QUICKLY? IF THEY SIGNED IRB SMART AND ARE ENROLLED IN THE EXCHANGE AND THEY HAVE AGREED TO TO USE STANDARD SUBCONTRACTS THROUGH THE NIH WHICH 97% OF THE CTSAs AGREED TO USE YOU CAN HAVE THOSE DOCUMENTS ALL OF THAT TAKEN CARE OF IN A DAY. AT LEAST IN THEORY. I CAN'T SPEAK TO OFFICE ARRANGEMENTS AT LITTLE ROCK BUT NOTHING FUNDAMENTALLY STOPPING IT FROM HAPPENING IN A DAY. >> I WOULD IMAGINE IF YOU OVERLAY SITES, THERE'S A MAJORITY -- >> IT OVERLAPS A LOT. >> THE NEXT FIVE-YEAR ROUND IS LIKELY TO BE ALL SMART IRB. >> YEAH. >> GREAT, THANK YOU. >> COMMENT S AND QUESTIONS. YOU OUTLINED WHAT YOU NEED TO START A TRIAL IN TERMS OF THE CONTRACT'S PIECE, I WOULD THROW BUDGET IN IT. THAT'S ONE OF THE THINGS THAT SLOWS IT DOWN BECAUSE PEOPLE WANT TO GET THAT PIECE OF IT. AND I SEE YOU'RE CONNECTING WITH TRANCEELERATE. WE SELF RECOGNIZE EACH OTHER IF YOU GO OUT AND SAY THIS TRIAL, THIS SITE IS READY TO GO CAN CTSA SITES THAT TYPICALLY SHOULD BE NO PROBLEM. THERE'S THE INVESTIGATOR PORTAL, COMMUNICATION ABOUT THE STATUS OF IRB APPROVAL SHOULD BE INSTANTANEOUS, ELECTRONIC TO EVERY SITE LINKED TO THE INVESTIGATOR PORTALS BEING BUILT. ELECTRONIC INFORMED CONSENT PROCESS CAN DOVETAIL. COMMON PROTOCOL TEMPLATES AND THINGS OF THAT NATURE. SO I THINK YOU'RE POISED HERE, I KNOW IT'S TOUGH TO EXPECT YOU TO DELIVER WITH NO BUDGET, THE CTSA, THE NCATS WAY. >> THAT'S RIGHT. >> BUT THOSE ARE THE ONES. THE OTHER THING, THE TWO QUESTIONS I HAD, ONE IS AROUND THE OPPORTUNITY FOR YOU, THIS NETWORK TO SERVE AS A RESOURCE FOR DIFFICULT TOPICS, WE TALKED ABOUT TISSUE CHIPS EARLIER, WHERE AN IRB IS GOING TO WANT TO SEE THE TYPICAL RAT AND CAT DATA THEY HAVE ALWAYS SEEN, NOW WE'RE GOING TO GIVE THEM TISSUE DATA, ORGAN ON A CHIP DATA, CAN WE PRE-POSITION THAT WITH A SOPHISTICATED NETWORK LIKE YOU'RE BUILDING SO YOU'RE ALREADY UNDERSTANDING THE ISSUES ON BEHALF OF OTHERS THAT ARE DOING THIS? AND THEN THE LAST BUT NOT LEAST QUESTION, HOW QUICKLY ARE YOU PLANNING TO GO GLOBAL WITH THIS? >> WELL, LET ME ANSWER THAT BECAUSE WE'VE GONE GLOBAL. IN SO FAR AS FWA HOLDING INSTITUTIONS EXTERNALLY, AS IN FINLAND AND A COUPLE OF OTHER PLACES HAVE SIGNED. SO THE CHALLENGE IS THAT THIS IS BUILT AS A RECIPROCAL AGREEMENT SO ONCE YOU SIGN YOUR PART OF THE TREATY YOU CAN RELY OR REVIEW. MOST INSTITUTIONS HERE ARE NOT COMFORTABLE REVIEWING FOR REGULATIONS OUTSIDE THESE WALLS. MOST. I MEAN, SOME DO. BUT IN TERMS OF THE OTHER WAY AROUND THAT WE CAN REVIEW IF THEY CAN REVIEW FOR US BECAUSE THEY HAVE AN FWA AND THEY KNOW HOW THEY ARE GOING TO BE -- THEY KNOW OUR RULES, THAT WORKS. AND IN SO FAR AS AN INSTITUTION CAN THEN VALIDATE THAT OUR REVIEW IS SUFFICIENT, OR PROVIDE, QUOTE, THE LOCAL CONTEXT. THIS IS STARTING IN -- WE'RE STARTING TO WORK ON THIS IN PEDIATRICS AS AN INTERNATIONAL COLLABORATION, IS TO HAVE INDIVIDUAL COUNTRIES, REGULATORY AGENCIES OF THE COUNTRY SIGN OFF ON A COMMON PROTOCOL. SO THAT WE HAVE ONE REVIEW AND STATE IN THE CASE OF GERMANY. WE CAN GET INTO THE DETAILS BUT -- AND THEN IT OKAY. >> I THINK AGAIN NOT TO KEEP HARPING ON TRANSELERATE, THINK IT IS A READY-MADE GROUP TO HELP WITH THE INTERNATIONAL COMMUNICATION. >> WE SHOULD TALK OFF LINE. >> THE OTHER PIECE WHICH IS NOT PART OF TRANSELERATE BUT WAS CREATED TO INTERACT WITH TRANSELERATE THAT YOU MAY NOT BE AWARE OF IS CRO FORUM. SO IT'S A CLUSTER OF MAJOR INTERNATIONAL CROs THAT CONDUCT CLINICAL TRIALS THAT THEY WOULD ALSO BE ANOTHER RESOURCE TO THINK ABOUT IN TERMS OF BEING ABLE TO -- WHAT BARRIERS AND OBSTACLES DO THEY GO THROUGH. >> I'LL FOLLOW UP WITH YOU, IF THAT'S OKAY. >> I HAD A FLASHBACK TO WHEN I WAS DESCRIBING THE REGULATORY SYSTEM IN DEVELOPING COUNTRIES TO A SENIOR LEADER OF MY ORGANIZATION. THEIR COMMENT WAS IT SOUNDS LIKE A JOBS PROGRAM FOR CHILD KILLERS. WHICH WAS A BIT STARK BUT I THINK MEGAN AND OTHERS HAVE, YOU KNOW, KIND OF ALLUDED TO THAT. I THINK THIS IS ONE OF THOSE THINGS WHERE WE REALLY DO HAVE TO LOOK AT WHAT IS OUR PURPOSE OF DOING THESE TYPES OF THINGS. IF IT IS TO GET, YOU KNOW, TO MOVE FAST BUT YET SAFE, THERE ARE PROBABLY MANY MORE EFFICIENT WAYS TO DO THAT. I'VE SEEN SOME BUT DIDN'T SEE A LOT OF IT. CHRIS, TO YOUR POINT, WHAT COULD SLOW US DOWN, YOU'VE HIGHLIGHTED SOME THINGS BUT PERHAPS NOT ALL. AND I RECOGNIZE IT'S A QUICK FORUM THAT WE HAVE HERE BUT I WOULD REALLY ENCOURAGE YOU TO THINK ABOUT WHAT YOUR CASE FOR CHANGE IS, EVEN TO THE POINT WHERE WE GO, WELL, IN YOUR CURRENT WAY OF DOING IT WHAT DOES IT COST IN TERMS OF TIME, MONEY, PEOPLE, THOSE TYPES OF THINGS, BOTH THE PREP TIME, REVIEW TIME, FOLLOW-UP TIME FOR QUESTIONS, I WOULD IMAGINE THAT THAT IS AN ENORMOUS AMOUNT OF EFFORT THAT GOES INTO IT. THE OTHER THING IS JUST THINKING ABOUT THE SPONSORSHIP SO WHAT TYPE OF SPONSORSHIP DO YOU NEED AT DIFFERENT INSTITUTIONS OR DIFFERENT ORGANIZATIONS LIKE THE NIH TO PUSH THIS THROUGH BECAUSE IF YOU WANT TO MAKE A CHANGE, IT'S BEEN WELL DOCUMENTED THAT YOU NEED STRONG ACTIVE SPONSORSHIP, WHETHER IT'S THE DEAN OR THE DIRECTOR OF THE NIH OR SOMEBODY LIKE THAT, IF THEY WAVE THEIR MAGIC WAND THINGS TYPICALLY HAPPEN. IF YOU DON'T HAVE THAT PROPER SPONSORSHIP NO MATTER WHAT YOU TRY TO DO YOU MAY GET IT DONE BUT IT'S GOING TO BE A REALLY LONG TIME DOING IT. SO THOSE ARE JUST A COUPLE OF THINGS THAT I WOULD THINK ABOUT. AND I THINK -- I USE A BROAD DEFINITION OF INNOVATION, ONE THAT'S A NEW APPROACH TO ACHIEVE SOMETHING PREVIOUSLY BEEN REALLY DIFFICULT TO DO. SO WHETHER IT'S, YOU KNOW, TISSUE ON CHIPS IN SPACE OR IMPROVING THE IRB PROCESS, I WOULD PUT THOSE BOTH IN THE INNOVATIVE SPACE AND THE THIRD MIRACLE FOR CHRIS' CANONIZATION WOULD BE TO BRING TO THIS GRANTS AND CONTRACTS. [LAUGHTER] I'LL STOP WITH THAT. >> TO THE TISSUE ON THE CHIP, THE QUESTION YOU HAD PREVIOUSLY, WHICH WAS HOW DO YOU GET IRBs TO UNDERSTAND THIS, ONE OF THE NICE THINGS ABOUT HAVING CENTRAL IRBs, YOU COULD IN THEORY AT LEAST FIND ONE THAT YOU WANT TO FOCUS THOSE KINDS OF STUDIES IN THAT IRB SO THAT THEY ARE ALREADY INTRODUCED TO THE CONCEPTS, LEARNED THEM AND JUST OF YOU JUST TRAIN THAT IRB. HARRY AND I WERE TALKING ABOUT THIS THIS MORNING, TO YOUR QUESTION ABOUT SPONSORSHIP, A LOT OF WHAT WE'RE TALKING ABOUT NOW COULD NOT HAVE HAPPENED WITHOUT THE BASIS OF A CTSA PROGRAM BECAUSE WITH LEADERS AT EACH MAJOR INSTITUTION IN POSITIONS OF NOT ALWAYS AUTHORITY BUT CERTAINLY BULLY PULPIT AND THE GRANTS ARE LARGE SO THAT COUNTS TOO. AND SO WHEN THAT PERSON, THAT P.I. SAYS OUR INSTITUTION NEEDS AGREEMENT OR AT LEAST PRESSURED BY NCATS TO DO IT, THINGS HAPPEN AND SO THAT'S THE PLATFORM UPON WHICH THE REST OF THIS CAN GROW. >> I THINK ONE ADDITIONAL THING WE DIDN'T SAY WHICH IS WE'RE EARLY IN DRIVING USE. IF WE COME BACK IN TWO YEARS AND THERE HAVE BEEN 4,000 RELIANCE AGREEMENTS WHICH IS VERY POSSIBLE, AND ALL THE OUTCOMES THAT CAN BE MEASURED OFF THAT, THAT'S WHERE THE TRANSFORMATIVE MOMENT IS. SO THERE'S A LOT OF THINGS TO BE DONE, BUT RIGHT NOW IT IS THE DISSEMINATION MEASUREMENT AND SHOWING PEOPLE, I'M GETTING IT, I ACTUALLY THINK THE STORY NEEDS TO BE TOLD TO THE PUBLIC IN SOME WAY. I THINK YOU KNOW PATIENTS ALL OVER THIS COUNTRY WHO STRUGGLE TO GET ON TRIALS, WHO WISH THEY HAD ACCESS, NEED TO KNOW THIS STORY. AND I'D LOVE TO HEAR SOME THOUGHTS ABOUT HOW THAT STORY SHOULD COME OUT AND WHERE. >> I JUST GO BACK TO BERNARD, YOUR POINT ABOUT THE LITTLE ROCK MODEL. WHY CAN'T YOU ENROLL WHEREVER THE STUDY IS? WHY THAT THIS HALLOWED MEDICAL CENTER MODEL, WHY CAN'T WE BREAK THAT DOWN? ? >> YOU COULD ENROLL ANYWHERE BUT IF HAVE YOU THE EXPERIMENTAL DRUG DISPENSED OUT OF LITTLE ROCK YOU'RE LOCKED INTO THAT INSTITUTION UNLESS YOU CAN AFFORD TO TRAVEL TO THAT INSTITUTION. >> OR SEND THE DRUG. >> NEW THEORY YOU COULD MAKE THAT WORK. >> THAT HAS PROBLEMS FOR OTHER REASONS. YOU CAN'T DO THAT. LIKE MEDICAL LEGAL REASONS, NOT IRB REASONS. >> WHAT'S THAT? >> SOMEBODY HAS TO GIVE THE DRUG. >> OKAY. >> SOMEBODY THAT GIVES THE DRUG THAT FOLLOWS GCP, NOT JUST SOMEBODY WHO HAS AN M.D. DEGREE. >> THOSE PEOPLE ARE ALL OVER THE COUNTRY CERTIFIED TO DO THAT. YOU ALL TALK ABOUT THINGS LIKE -- THERE'S CARE DELIVERY AND PEOPLE WHO ARE REGULARATORILY TRAINED. WE CREATE BARRIERS, WE DON'T THINK OUT OF THE BOX. IT'S A MATTER OF FIGURING OUT HOW TO GET THE RIGHT DRUG IN THE HANDS OF THE RIGHT PERSON TO DELIVER THE DRUG. >> ABSOLUTELY. >> I THINK WE HAVE ANOTHER TEN MINUTES. IF I MAY, A COUPLE THINGS THAT WOULD BE GREAT -- >> WE DIDN'T GO ALL THE WAY AROUND. >> SORRY. >> YES, THANK YOU. THERE'S SOMETHING THAT I ACTUALLY WANT TO GIVE A DIFFERENT FLAVOR TO YOUR INITIAL QUESTION. >> MIC. >> YEAH, I'M NOT CLOSE ENOUGH. SORRY. TO YOUR INITIAL QUESTION. >> CHECK IF YOUR MICROPHONES ARE ON. PETRA, CAN YOU TURN YOURS? >> I DON'T KNOW WHY IT GOES OFF. IT'S OKAY. I THINK IT'S A GREAT OPPORTUNITY. WHY? BECAUSE IN EVERYTHING THAT WE'RE GOING TO DO IN THE FUTURE, WE NEED AN ENTITY THAT IS TRUSTED BY THE PEOPLE. AND I THINK AN IRB, PARTICULARLY WHEN CENTRALIZED, STREAMLINED, STANDARDIZED, CAN BE THAT ENTITY. LET ME JUST DRAW THE NEXT POINT HERE. WE NEED HEALTH DATA DELIBERATION, NO MATTER HOW WE DO IT, THAT ALSO MEANS PATIENTS WHO WANT TO ENROLL OR WANT TO GAIN ACCESS, RIGHT NOW EVEN IN A HIGHLY RESEARCHED AND ACTIVE FIELD LIKE CANCER, WE HAVE ONLY 3% OF PATIENTS HAVE ACCESS TO INNOVATIVE DRUGS OR TREATMENTS, RIGHT? THAT'S PAINFUL TO KNOW, PARTICULARLY WHEN YOUR ATTENTION OR FOR ANYONE, AND THAT'S SOMETHING Y OU NEED TO CHANGE. CONDUCTING CLINICAL TRIALS, WE CONDUCT CLINICAL TRIALS IN A BUBBLE THAT HAS VERY LITTLE TO DO WITH THE REAL WORLD. AT SOME POINT WE JUMP THAT LEAP AND BRING THE DRUGS INTO THE MARKET AND CMS OR INSURANCE COMPANIES DECIDE WHETHER TO REIMBURSE, A SIGNIFICANT IMPACT WHETHER THIS DRUG IS AVAILABLE AND SUCCESSFUL, THIS IS SOMETHING WE CAN OVERCOME. AND I THINK THIS EFFORT AS MUCH AS IS DONE IN CONTEXT OF A TRADITIONAL APPROACH HAS THE SEED TO BE A VERY IMPORTANT ENTITY FOR THE FUTURE, NAMELY THAT FOR THE INDIVIDUALS, THE PEOPLE, THE PATIENTS, TO WORK WITH. BECAUSE IT'S THE ENTITY OF TRUST REPRESENTING PATIENTS. THERE'S SOME OTHER ELEMENTS WE NEED TO CONSIDER, RIGHT? WE ALSO CAN IN THE CONTEXT OF CTSA PROBABLY CONTEMPLATE HOW THE CTSA CAN DEVELOP INTO A PLATFORM FOR CONTINUOUS PLATFORM TRIALS THAT INCORPORATE THE CRITERIA FOR PRAGMATIC TRIALS BECAUSE, AGAIN, WE CANNOT CONTINUE TO CREATE TWO DIFFERENT WORLDS OF CLINICAL TRIALS. I THINK THIS IS THE OPPORTUNITY AND I'M VERY OPTIMISTIC THAT WE CAN CONSIDER ALL IN THE SPEED AS HEALTH AND DATA AND NEW ENTITIES EVOLVE AND AS WE EMPOWER PEOPLE AND PATIENTS TO BE PART, CRITICAL PART OF THAT. THIS CAN PLAY A VERY SIGNIFICANT POSITIVE ROLE. SO I THINK -- >> CAN I JUST COMMENT ON ONE RISK OF THE SYSTEM THAT I'M VERY CONCERNED ABOUT WHICH IS THAT WHEN YOU HAVE ONE IRB REVIEWING ON BEHALF OF EVERY -- YOU KNOW, 50 SITES OR 23 SITES, IF SOMETHING IS FOUND TO BE IN ERROR ON THAT REVIEW, THAT IRB, THAT INSTITUTION, IS LOOKING AT THE BARREL OF THE GUN AND THE MEDIA SORT OF TIRADE. THAT HAPPENED WITH THE SUPPORT TRIAL, AND 23 IRBs REVIEWED AND APPROVED. AND THERE WAS STILL A PROBLEM THERE. AND YOU KNOW, THIS WILL HAPPEN WITH PUBLICS AND OTHER WONDERFUL SORT OF WATCH DOGS, AND WE NEED TO BE PREPARED TO PROTECT, YOU KNOW, A JOB WELL DONE EVEN IF MISTAKES ARE MADE BECAUSE MISTAKES WILL BE MADE. THAT'S NUMBER ONE. AND ON THE WISH LIST THERE, FOR WHAT I THINK NCATS CAN TAKE A LEADERSHIP ROLE IN HERE IS SETTING UP FIRST THE DATA STANDARDS WHICH YOU'VE TALKED ABOUT BUT HASN'T BEEN DONE, SECOND RETURN OF RESULT IT'S TO PARTICIPANTS WHICH WOULD BE ABSOLUTELY IN YOUR, YOU KNOW, SORT OF MISSION TO DO AND WE DON'T DO IT, AND THEN ACCESS OF THE PATIENTS TO THEIR DATA. >> I JUST WANTED TO SUGGEST BECAUSE IF YOU MIGHT WANT TO ENCOURAGE THE PANELISTS, BECAUSE SOME OF THEM HAVE TO LEAVE VERY SHORTLY TO SPEAK BRIEFLY ABOUT THE FUTURE, WHAT ARE NEXT STEPS AND YOUR VISION HOW THIS MIGHT PLAY OUT. >> I'LL SAY I'VE TALKED ABOUT A LOT IN PIECES BUT THE IDEA IS ON THE LINES OF HOW DO YOU GET A PATIENT IN A STUDY RIGHT AWAY. AND SOME OF IT IS A PACKAGE THAT YOU CAN SEND TO A SITE THAT THEY CAN HANDLE IN QUICK FASHION AND THAT'S THE MODEL MOST OF US CAN SEE HAPPENING. I CAN SEE HAPPENING IN A MONTH FROM NOW, EVEN RIGHT NOW, TODAY IT COULD HAPPEN IN SOME SITES THAT ARE ALL SIGNED UP. THE ELECTRONIC STUDY, STUDY DONE WITHIN ELECTRONIC SYSTEMS, WE HAVE THOSE GOING ON NOW AS WELL. WE JUST COMPLETED ONE WHERE WE DID A CLUSTER RANDOMIZED TRIAL OF FLUID ADMINISTRATION TO PATIENTS IN CRITICAL CARE, LACTATED RINGERS VERSUS NORMAL SALINE, AGE-OLD QUESTION NEVER GETTING THE FLUIDS EVERY DAY. I CAN'T TELL YOU. >> WHAT'S THE ANSWER? >> I CAN'T TELL YOU. >> YOU'RE KILLING ME! >> IT'S LIKELY TO BE PUBLISHED IN A REGIONAL JOURNAL IN THE NEXT THREE MONTHS. ALL ELECTRONICALLY, YEAH. >> HOW DID YOU CONSENT THE PATIENT? >> IT WAS A CLUSTER RANDOMIZED TRIAL WITH WAIVER OF CONSENT. >> USING ELECTRONIC DATABASE YOU WERE ABLE TO WAIVE CONSENT? >> BECAUSE IT WAS MINIMAL RISK, DIDN'T COMPROMISE HEALTH AND WE'LL BEING OF PATIENT, RESULTS COULD BE PROVIDED WHEN STUDY WAS OVER. >> SAME CRITERIA WE USE FOR WAIVING CONSENT WHETHER WE HAVE A CENTRALIZE IRB OR SINGLE IRB REMAINS? >> IT WOULD HAVE HAD TO BE WAIVER OF CONSENT FROM EVERY IRB HAD WE NOT HAD THE SYSTEM IN PLACE. >> I'M MAKING A POINT THAT DOESN'T CHANGE WHEN WE GO TO USING DATA SYSTEMS. YOU SAW THE STUDY THAT CAME OUT IN THE NEW ENGLAND JOURNAL YESTERDAY ABOUT USING DATABASES FOR RANDOMIZED CLINICAL TRIALS. RIGHT? AND SO THEY TALKED A LARGE PART ABOUT HOW WE'RE GOING TO GET THE CONSENT, DO YOU HAVE TO HAVE CONSENT OR CAN YOU WAIVE CONSENT? SO THAT'S ONE OF THE FUTURE THINGS I WOULD LIKE FOR YOU ALL TO THINK ABOUT AS YOU'RE THINKING ABOUT THIS SMART IRB. >> WE COULD TALK ABOUT THAT BUT I KNOW THE CLOCK IS TICKING. I HAVE AN ANSWER TO THAT. >> THE QUESTION, IF YOU HAD REMARKS ON WHAT YOU SEE AS THE VISION OR NEXT STEPS FOR IRB COLLABORATION. >> NEXT STEPS, I THINK WE PUT UP -- I ABSOLUTELY BELIEVE THAT IN THE NEXT COUPLE OF YEARS WHAT WE HAVE TO DO IS, ONE, I THINK WE SHOULD GET THE LARGEST NUMBERS OF SITES, BRING PEOPLE IN INCLUSIVELY, THAT COULD BE, I THINK THE SECOND THING IS IF WE COULD COME TO ONE SYSTEM WHERE PEOPLE USE IT, ONE INFRASTRUCTURE SYSTEM, AND THREE, I THINK THAT THE NEXT STEP IS HARMONIZATION OF SOME PROCESSES WHERE PEOPLE THINK THAT WE REALLY CAN WORK TOGETHER AND BRING IT TOGETHER. THE SINGLE BIGGEST CHALLENGE IS USE. I THINK IT'S NOT AN OBJECTIVE. WE MUST DO IT. AND THAT SITS ON THE P.I.s. AND, YOU KNOW, I'LL BRING IT UP AT THE P.I. MEETING. WE'VE GOT TO MAKE THIS WORK. AND IT DOESN'T HAVE TO BE -- (INAUDIBLE). >> (INAUDIBLE). >> SO I THINK THAT THERE ARE A FEW DIFFERENT SORT OF LEVELS THAT I WOULD THINK ABOUT. ONE IS I THINK WE HAVE A LOT OF WORK TO DO ON WHAT WE'RE DOING NOW. WE HAVE TO REWRITE THE AGREEMENT. WE HAVE TO BRING IN, YOU KNOW, OTHER -- AND UNIFY VIA DoD, INDUSTRY, FIGURE OUT AN INTERNATIONAL MODEL, ALL THOSE THINGS, LIKE A LOT OF BLOCKING AND TACKLING THAT'S PRETTY COMPLICATED. AND THEN OF COURSE THE HARMONIZATION, AND ALL THAT. I DO THINK THAT WE SHOULD SOMEHOW OPERATIONALIZE A MORE CREATIVE STRATEGIC GROUP TO THINK ABOUT HOW TO ENABLE THE KIND OF SORT OF STUDIES WE WANT TO SEE, THAT WE TALK ABOUT ARE IN THE FUTURE BUT WE'RE ABLE TO DO THEM TODAY, IF WE WERE ABLE TO DO THEM. AND WE JUST, YOU KNOW, DON'T HAVE THE REGULATIONS THAT ALLOW IT OR WE DON'T HAVE THE INFRASTRUCTURE TO ALLOW IT. AND THE THIRD PART OF THAT I THINK IS A MUCH BETTER EDUCATIONAL AND ENGAGEMENT EFFORT, SO THAT OUR PUBLIC STANDS WITH US ON -- AND UNDERSTANDS THE VALUE OF RESEARCH AND WHY WE'RE DOING WHAT WE'RE DOING GOING FORWARD. AND TO DO THAT I THINK WE'VE GOT TO SIMPLIFY THE MESSAGE, NOT USE THE LANGUAGE WE USE. >> SO I KNOW THAT -- I DON'T KNOW WHAT HAPPENED WITH IT BUT I KNOW RCMI, RESEARCH CENTERS OF MINORITY INSTITUTIONS, THE TRANSLATIONAL RESEARCH NETWORK, PUT IN A SUPPLEMENT, I BELIEVE, TO NCATS TO ADVANCE TRAINING BECAUSE WE'VE BEEN DOING IT IN OUR IRB RECIPROCITY PROCESS FOR THE LAST FOUR YEARS, WITHIN OUR 18 INSTITUTION COALITION. AND I KNOW WE PUT IN A SUPPLEMENT TO GET FUNDING BECAUSE AT OUR ANNUAL CONFERENCE IN A COUPLE WEEKS WE HAVE ALL THE 18 SCHOOLS AND IRB LEADERS COMING FOR TRAINING. NOW, I HAVE NO IDEA WHAT HAPPENED WITH THAT BECAUSE I HAVE TO BE SEPARATED FROM IT, BUT EVEN IF IT DIDN'T GET FUNDED THAT WOULD BE A GREAT OPPORTUNITY TO HAVE 18 OF THE MINORITY INSTITUTIONS WHERE THEY WOULD GET -- THEY ALL HAVE -- WE HAVE ALL SIGNED ON OUR AGREEMENT FOR OUR IRB RECIPROCITY, AND WE HAVE A CENTRAL IRB WE DO STUDIES WITHIN AND LEE KNOWS THIS BECAUSE LEE IS ON -- OUR CHAIR OF OUR GROUP. >> OKAY. ANY LAST WORDS FROM ANYONE? >> THANK YOU SO MUCH. >> THANK YOU. [APPLAUSE] >> OKAY. SO WITH THAT WE ARE GOING TO ADJOURN, DR. MARKS AND I WILL GAVEL US OUT. ONE, TWO, THREE. OOH, NOT AS GOOD AS THIS MORNING BUT WE'RE -- OKAY. SO THE OPEN SESSION IS ADJOURNED. THANK YOU ALL. THOSE OF YOU WHO NEED TO STAY FOR THE CLOSED SESSION, I THINK YOU KNOW WHO YOU ARE. IF YOU HAVE ANY QUESTIONS ABOUT WHETHER YOU ARE ONE OF THOSE PEOPLE, ASK ANNA. FOR THOSE LEAVING US, THANK YOU, THANK YOU, THANK YOU. AND WE'LL SEE YOU NEXT TIME. >> WE ANTICIPATE FOUR OF FIVE FULL MEMBERS WILL STAY AND ANY AD HOCS ARE WELCOME, WE CAN ACCOMMODATE HAVING YOU IN THE ROOM DURING THE SESSION. [END OF PROGRAM]