I WANT TO WELCOME EVERYBODY TO THE NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES ADVISORY COUNCIL AND CURES ACCELERATION NETWORK REVIEW BOARD. AS IS OUR CUSTOM, THE "CAN" CHAIR AND I WILL CO-GAVEL THIS MEETING INTO ORDER. SO LYNN MARKS IS GOING TO DO THAT AS SOON AS HE STOPS SIGNING IN. HERE WE GO. ONE, TWO, THREE. ALL RIGHT. NICE JOB. SO THANK YOU. THANKS FOR BEING HERE, EVERYBODY. WE HAVE A LOT TO DO TODAY SO LET'S GET RIGHT INTO THINGS. I I WANT TO RECOGNIZE EVERYBODY WHO IS HERE, TELL YOU WHO IS HERE AND ISN'T GOING TO BE WITH US TODAY. SO FULL MEMBERS IN ATTENDANCE ARE DAN HARTMAN FROM GATES FOUNDATION, FROM MEDTRONIC, BRAD MARGUS, PATIENT ADVOCATE AND BIOTECH CEO, MEGAN O'BOYLE WHO IS ALSO A PATIENT ADVOCATE, ALAN PALKOWITZ WHO IS A CHEMIST. >> THERE ARE MANY WAYS COMMUNITIES CAN SUPPORT CHILDREN WITH JOURNEY TO GOOD HEALTH >> WE SUPPORT THAT. AH, MOREHOUSE SCHOOL OF MEDICINE, THAT'S WHERE IT'S COMING FROM. >> DID YOU KNOW SEPTEMBER IS NATIONAL CHILDHOOD OBESITY MONTH? >> NOW THAT YOU KNOW THIS IS CHILDHOOD OBESITY MONTH AND YOU'RE SUPPOSED TO EAT MORE FRUITS AND VEGETABLES WE'LL RETURN TO OUR PROGRAM. ALAN PALKOWITZ, VALERIE MONTGOMERY RICE IS THE DEAN AT MOREHOUSE, WILL BE JOINING US SHORTLY. AND THEN WE HAVE TWO "CAN" REVIEW BOARD REPRESENTATIVE MEMBERS, ROSENBLATT AND STONER. LIZ RIGHT THERE, MIKE RIGHT THERE. I BELIEVE KAREN READY, WHO IS ALSO A "CAN" RB REPRESENTATIVE IS ON THE PHONE. KAREN, ARE YOU ON THE PHONE? >> (INAUDIBLE). >> THAT WAS VALERIE, NOT KAREN. CAN YOU FIND OUT IF VALERIE IS THE PHONE. AND WE HAVE EX OFFICIO MEMBERS, YOU KNOW WHO EVERYBODY IS, FRANK WECOLD FROM FDA, AND NAOMI, WELCOME, WHO IS FROM THE V.A. SHE'S A DEPUTY DIRECTOR OF V.A.'S HEALTH SERVICES RESEARCH AND DEVELOPMENT SERVICE, AND WAS AT CMS IN THE INNOVATION CENTER BEFORE THAT, AND HAS BEEN AT SAMHSA AND OTHER PLACES IN THE FEDERAL GOVERNMENT, SO WELCOME. SHE'S STANDING IN FOR RACHEL RAMONI FROM THE V.A. RICHARD DICKINSON FROM NATIONAL SCIENCE FOUNDATION IS HERE AS WELL. SO, I THINK DID I GET EVERYBODY? I THINK I DID. NOT PRESENT TODAY, KALPANA MERCHANT AND TODD SHERER, THEY WILL BE BACK WITH US NEXT TIME. MAYBE I CAN DO THIS. LET'S SEE. OKAY. JOINT MEETING, OPEN SESSION AGENDA, CALL TO ORDER, WHICH LYNN AND I JUST DID. THIS IS THE AGENDA, APPROVAL, INTRODUCTION OF NEW STAFF, DIRECTOR'S REPORT, AND THE CURES ACCELERATION NETWORK UPDATE AND THEN WE'RE GOING TO HAVE LUNCH I BELIEVE. AND THEN AFTER LUNCH WE HAVE COMPREHENSIVE UPDATE ON ORDR, BECAUSE WE REALIZE WE'VE NEVER DONE THAT AND BECAUSE THERE'S A LOT GOING ON IN THIS SPACE WHICH WE WOULD LIKE TO TELL YOU ABOUT BUT ALSO GET YOUR THOUGHTS ON. ARE WE DOING THE RIGHT THINGS, OF ALL THE THINGS WE COULD DO IN THIS SPACE ARE THESE THE RIGHT THINGS WE'RE DOING. AND THEN WE HAVE TWO CONCEPT CLEARANCES WE HAVE TO DO AND WE'LL REMIND WHAT YOU THAT MEANS WHEN WE GET THERE. AND THEN OUR SPECIAL TOPIC, I WON'T LEAVE YOU IN SUSPENSE, I FEEL LIKE THAT'S MEANT TO BE A SURPRISE OR SOMETHING. THAT IS CLINICAL INFORMATICS. A LOT GOING ON IN THE INFORMATICS MLAI SPACE AND WE'LL HAVE A COUPLE -- A NUMBER OF PRESENTATIONS AT COUNCIL AND THE CAN BOARD ABOUT INFORMATICS AND I.T. AND ML AND FOCUS ON CLINICAL AND DO PRE-CLINICAL AT A FUTURE MEETING. OKAY. ALL OF THAT TODAY. NOW ANNA WILL GO THROUGH LOGISTICS AND CONFIRM FUTURE MEETING DATES. >> THANK YOU, CHRIS. THE MINUTES FROM THE MADE 2019 JOINT MEETING ARE AVAILABLE. COULD WE HAVE A MOTION TO APPROVE THE MINUTES OF THE MAY MAY 2019 JOINT MEETING? >> SO MOVED. >> SECOND? >> SECOND. >> ALL IN FAVOR? >> AYE? ANY OPPOSED? ANY ABSTENTIONS? THE MINUTES ARE APPROVED. THERE ARE NO REMAINING JOINT MEETING DATES IN 2019. IN 2020 HAPPENING ON JANUARY 16, MAY 14, SEPTEMBER 17. IN 2021, JANUARY 14, MAY 20, SEPTEMBER 23. THE REMAINING MEETING IN 2019 IS A CAN-ONLY MEETING IN DECEMBER 13, IN 2020 CAN-ONLY MEETING IS DECEMBER 11 AND IN 2021 THE CAN MEETING IS ON DECEMBER 10. >> WE'RE GOING TO READ A FEW KNEW STAFF WE WANT TO INTRODUCE TO YOU. WE HAVE A NUMBER OF PEOPLE WHO ARE GOING TO STEP UP AND DO THAT. FIRST IS RANDY REDMOND, DEPUTY ETHICS OFFICER, HE'S GOING TO INTRODUCE SOMEBODY FROM OFFICE OF ADMINISTRATIVE MANAGEMENT. RANDY? >> THANK YOU. DEPUTY EXECUTIVE OFFICER, NOT ETHICS OFFICER. THANK YOU. I'M FLATTERED. GOOD MORNING, EVERYBODY. IT'S MY GREAT PLEASURE TO ANNOUNCE THAT ZOE ANN COPELAND JOINED NCATS AS CHIEF OF ADMINISTRATIVE SERVICES BRANCH, AND COMES FROM NABIB, DEPUTY EXECUTIVE OFFICER, AND HAS BEEN WITH US FOR A COUPLE OF YEARS AT THIS POINT ON DETAIL. THERE'S THE SLIDE. A COUPLE YEARS NOW ON DETAIL. FIRST AS A SPECIAL ADVISER TO THE E.O. AND MOST RECENTLY ACTING CHIEF OF ADMINISTRATIVE SERVICES BRANCH. WE STARTED MANY YEARS AGO AT NIH, I'VE KNOWN HER A VERY LONG TIME, AND I PROMISE YOU WE ARE VERY FORTUNATE TO HAVE HER ON BOARD AT NCATS. ZOE ANN, WELCOME TO NCATS. >> THANK YOU. >> THANKS, RANDY. WELCOME, ZOE ANN. ZOE ANN HAS BEEN THROUGH AN EXPERIENCE, YOU KNOW HOW LONG IT TOOK YOU TO GET APPROVED TO DO THIS JOB? SHE'S BEEN DOING THE SAME, EQUIVALENT IN HER POSITION, FOR THE LAST COUPLE YEARS. IT'S GREAT TO HAVE HER OFFICIAL. JESSICA FOGELBADGER, DIRECTOR OF EDUCATION BRANCH IS GOING TO INTRODUCE A NEW PERSON FROM HER BRANCH. >> IT'S MY PLEASURE TO INTRODUCE DR. AMANDA VOGEL, COMES TO US MOST RECENTLY FROM NATIONAL CANCER INSTITUTE. SHE'S BEEN THERE WITH NCI FOR TEN YEARS, MOST RECENTLY IN THE CENTER FOR GLOBAL HEALTH AND BEFORE THAT IN THE BEHAVIORAL RESEARCH PROGRAM, DIVISION OF CANCER CONTROL AND POPULATION SCIENCES. SO I'M EXCITED FOR AMANDA TO JOIN OUR BRANCH. SHE'S BRINGS A UNIQUE COLLECTION OF EXPERTISE, AN EXPERT IN TEAM SCIENCE, AND ONE THING YOU MAY BE AWARE OF IS TEAM SCIENCE TOOLKIT, SHE WAS A LEAD PERSON AGGREGATING THAT INFORMATION, ALSO LEAD AUTHOR ON MANY OF THOSE MATERIALS. IN ADDITION HAS EXPERTISE IN MIXED METHODS EVALUATIONS SO WE'RE DELIGHTED TO BRING THIS EXPERIENCE AND AMANDA TO THE OFFICE OF POLICY COMMUNICATION AND EDUCATION. >> THANK YOU. [APPLAUSE] WELCOME, AMANDA. RIGHT, NANA HAS MANY HATS, DIRECTOR OF OFFICE OF GRANTS MANAGEMENT AND HAS AN INTRODUCTION. >> I'M PLEASED TO ANNOUNCE THE APPOINTMENT OF THE NEW POSITION IN THE OFFICE OF THE DIRECTOR, OFFICE OF THE GRANTS MANAGEMENT, QUINNA COMES FROM SCIENTIFIC REVIEW FOR THE PAST FOUR YEARS, GAINED EXPERIENCE WITH THE VARIETY OF ACTIVITY CODES, CLINICAL, SOLICITATIONS, OVERALL PROCESS OF INITIATIVE DEVELOPMENT. SHE COORDINATED PRODUCTION, REVIEW AND NIDCR APPROVAL PROCESS LEADING TO PUBLICATION OF FUNDING OPPORTUNITIES AND NOTICES IN THE NIH GUIDE. PRIOR TO THAT SHE WORKED IN BOTH REVIEW AND PROGRAM GROUPS AT NINDS, NIH O D AND NATIONAL ACADEMY OF SCIENCES. SHE BRINGS EXPERIENCE AS CLINICAL RESEARCH, REGULATORY AFFAIRS SPECIALIST AND FREELANCE MEDICAL WRITER, WHICH IS A BONUS. WE'RE VERY MUCH LOOKING FORWARD TO OPTIMIZING INITIATIVE MANAGEMENT PROCESS AT NCATS AND QUINNA WILL PLAY A CENTRAL CONTROL AS WE COLLABORATE WITH OUR PARTNERS. PLEASE JOIN ME IN WELCOMING QUINNA TODAY. [APPLAUSE] I'D LIKE TO TURN THE FLOOR OVER TO CHRIS FOR THE DIRECTOR'S UPDATE. >> ALL RIGHT. SO I THOUGHT I WOULD TRANSLATE FOR YOU THOSE ACRONYMS PEOPLE USE. WE MAY HAVE JUST FOR FUN, MAY TEST PEOPLE ON WHAT THE ACRONYMS ARE. NABIB, IS THE NATIONAL INSTITUTE OF THE BIOMEDICAL IMAGING AND BIOENGINEERING. NCI MOST OF YOU PROBABLY KNOW THAT'S THE CANCER INSTITUTE. NIDCR IS THE NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH. NOT TO BE CONFUSED WITH NIDCD, OR NICHD OR A VARIETY OF OTHER INSTITUTES WHICH I WILL NOT REGALE YOU WITH BUT SHE COMES FROM THE DENTAL INSTITUTE. OKAY. SO ONE FAREWELL, WE HAVE PEOPLE COMING AND GOING, AND SHARON TERRY WHO MANY, MANY OF US KNOW HAS SERVED ABLY ON THE CAN REVIEW BOARD FOR LAST SEVERAL YEARS, HER TERM HAS JUST ENDED LAST MONTH, SO SHE WON'T BE WITH US, AT LEAST OFFICIALLY, BUT SHE'S A MEMBER OF THE COMMUNITY SO WE'LL CONTINUE TO SEE HER. SHE'S THE PRESIDENT AND CEO OF GENETIC ALLIANCE. WHAT I'M GOING TO DO NOW IS JUST VERY QUICKLY I HOPE RUN THROUGH A FEW HIGHLIGHTS THAT I THOUGHT WAS IMPORTANT FOR YOU TO KNOW ABOUT WHAT'S GOING ON AT NCATS. I'M GOING TO DO IT BASED ON THIS ORGANIZATIONAL CHART, YOU MAY NOT HAVE SEEN THIS BEFORE, BUT ALSO THE DIRECTOR HAS A COUPLE OF TRANS-NIH PROGRAMS THAT LIVE OFF OF IT, COMMON FUND AND THE HEAL PROGRAM, COMMON FUND AND HEAL PROGRAM. UNDERNEATH THAT ARE OFFICE, GRANTS MANAGEMENT AND SCIENTIFIC REVIEW THAT ANNA RUNS, ALSO ADMINISTRATIVE MANAGEMENT, EXECUTIVE OFFICER, THAT'S WHERE RANDY WORKS AND KEITH, WHO IS OUR EXECUTIVE OFFICER. OPCE, POLICY AND COMMUNICATIONS AND EDUCATIONS, THREE BRANCHES, AND JESSICA FOGELBADGER RUNS THE EDUCATION BRANCH, PETTY BEGRUNE RUNS THE OFFICE, AND YOU HEARD ABOUT OUR SBIR PROGRAM. AND UNDER THAT ARE THE VARIOUS DIVISIONS, PRE-CLINICAL, CLINICAL, RARE DISEASES, AND THE CURES ACCELERATION NETWORK. SO, WE'RE GOING TO START WITH OPCE. WHAT'S GOING ON IN THAT SPACE. THIS IS THE STATE OF THE BUDGET. FANS OF THE PROCESS WILL KNOW IT'S UNUSUAL TO HAVE WHAT HAPPENED LAST YEAR WHICH WAS THAT WE ACTUALLY HAD A BUDGET BEFORE THE BEGINNING OF THE FISCAL YEAR. THAT'S THE WAY THE GOVERNMENT HAS DOING THIS. WITH RARE EXCEPTIONS SINCE THE CARTER ADMINISTRATION, THAT IS THAT THE PARTIES IN THE HOUSES CANNOT AGREE OR CHOOSE NOT TO AGREE AND THERE'S BRINGSMANSHIP. EVENTUALLY THEY PASS A BUDGET, USUALL MIDDLE OF FISCAL YEAR, AFTER THAT A CONTINUING RESOLUTION KEEPS US FUNDED. THAT FUNDS THE AGENCIES AT THE SAME TIME THEY WERE AT THE PREVIOUS YEAR, UNTIL THE APPROPRIATORS CAN AGREE AND THE HOUSE AND SENATE CAN AGREE ON A BUDGET AND THE PRESIDENT SIGNS IT. SO THAT'S PRETTY MUCH WHERE WE ARE NOW. WE ARE HEADING TOWARD A C.R. YOU CAN SEE THIS AT THE BOTTOM. IT'S LIKELY TO BE EITHER BETWEEN THANKSGIVING AND CHRISTMAS, SOMETHING LIKE THAT, IT'S NOT THE END OF THE WORLD. WE'RE USED TO DOING THIS. WE'VE DONE IT MANY YEARS, MOST YEARS ACTUALLY. ALL YEARS BUT ONE I'VE BEEN AT NIH IT'S BEEN THIS CASE. I MUST SAY, HOWEVER, THAT IT DOES CAUSE PROBLEMS. ALL OF YOU RUN ORGANIZATIONS. IF YOU DO NOT KNOW YOUR BUDGET FOR SURE UNTIL HALFWAY THROUGH THE YEAR IT'S HARD TO MAKE INVESTMENTS. I DON'T WANT TO MINIMIZE HOW HARD THIS IS ON STAFF AND GRANTEES, MEDICAL SCHOOLS AND INTRAMURAL LABS, BUT IT IS WHAT IT IS. I'LL GET TO THE HEARINGS IN A SECOND. THE HOUSE APPROVED ITS SUBCOMMITTEE AND APPROPRIATION COMMITTEE LABOR EDUCATION IN A MINI BUS, NOT AN OMNIBUS THAT CONSIDERED ALL OF THOSE CABINET AGENCIES TOGETHER. THE SENATE RELEASED THEIR BILL YESTERDAY, AND NIH DOES QUITE WELL. IT'S EITHER A $2 BILLION OR $3 BILLION INCREASE DEPENDING WHETHER IT'S THE HOUSE OR SENT, NCATS IS PROPORTIONAL TO THAT AS WELL. DON'T PAY TOO MUCH ATTENTION TO THESE BECAUSE THIS IS VERY MUCH IN PLAY. THE HOUSE AND SENATE ARE NOW GOING TO HAVE TO COME TOGETHER AND RECONCILE THE DIFFERENCES, THERE'S MANY IN THE REPORT LANGUAGE THAT GOES WITH IT. THE PRESIDENT HAS TO SIGN IT. BUT THIS IS THE CURRENT STATE OF PLAY. IF THIS WAS A THREE-ACT PLAY THIS WOULD BE ACT 2, SCENE 1, SO THERE'S QUITE A BIT MORE ACTION TO HAPPEN. HOPEFULLY BY THE TIME OF THE REVIEW BOARD MEETING IN DECEMBER WE'LL HAVE A BUDGET AND CAN TELL YOU ABOUT IT. A NICE THING HAS HAPPENED THIS YEAR. TRADITIONALLY, THE APPROPRIATIONS HEARINGS HEARD FROM ALL OF THE INSTITUTE DIRECTORS AT NIH, THAT ENDED ABOUT A DECADE AGO. AND USUALLY THERE ARE FOUR OR FIVE OR SIX INSTITUTE DIRECTORS THAT TESTIFY WITH DR. COLLINS AT THE APPROPRIATIONS SUBCOMMITTEES MEETINGS, AND I'VE DONE THAT A FEW YEAR AS WELL, BUT THIS YEAR THE HOUSE RUN BY HOUSE SUBCOMMITTEE, DELAURO FROM CONNECTICUT. SHE AND HER COMMITTEE WANTED TO HEAR FROM ALL THE NIH INSTITUTES THEY DON'T HEAR FROM. WE HAVE A GREAT GROUP, US, NABIB, NIMHD, THE NATIONAL INSTITUTE OF MINORITY HEALTH AND HEALTH DISPARITIES AND NATIONAL LIBRARY OF MEDICINE ARE GOING TO BE TESTIFYING. IT'S REALLY A GREAT GROUP OF DIRECTORS. THEY ARE ALL GREAT PEOPLE. I THINK IT WILL BE A GOOD HEARING, GOOD FOR NIH. AND GOOD FOR US. OKAY. SO, I THINK I MIGHT HAVE MENTIONED BEFORE, THE HHS HAS A NUMBER OF INNOVATION INITIATIVES RUN OUT OF CHIEF TECHNOLOGIST OFFICE. AND ONE OF THESE IS THE ACCELERATOR PROGRAM, LIKE I-CORPS, OR LIKE SHARK TANK, AND SO WE HAD A NUMBER OF APPLICANTS FROM NCATS, 19 PROJECTS AWARDED, THREE OF THE FOUR THAT WENT TO NIH CAME TO NCATS, WE GOT 75% OF THE AWARDS EVEN THOUGH WE MAKE UP 2% OF THE BUDGET WHICH MAKES ME PROUD. WE PRIDE OURSELVES ON INNOVATION AROUND HERE. IT'S NICE TO HAVE SOMEBODY ELSE RECOGNIZE THAT WE EXCEL IN THAT AS WELL. AND SO THESE ARE THE THREE THAT ARE BEING DONE. I WANT TO MENTION, THIS WORKSHOP THAT WAS HELD BACK IN JULY, I MENTIONED OUR REAL INTEREST AND INCREASING WORK IN THE AREA OF MACHINE INTELLIGENCE OR ARTIFICIAL INTELLIGENCE OR MACHINE LEARNING, DEEP LEARNING, THERE'S VARIOUS TERMS USED TO DESCRIBE THESE PROCESSES. AND ONE ASPECT OF THIS IN THE CLINICAL DOMAIN HAS BEEN IMPORTANT ISSUES ON HOW TO INCORPORATE THESE TOOLS INTO HEALTH CARE, AND PART OF THIS, THE WORKSHOP, WAS ABOUT THE ROAD BLOCKS TO IMPLEMENTING THIS KIND OF TECHNOLOGY. BUT ALSO THE ISSUES AROUND POTENTIAL BIAS OF THE OUTCOMES, DEPENDING ON THE DATA THAT GO IN, AND SO WE CO-HELD A WORKSHOP WITH NABIB AND NCI IN JULY, AND WE HAD A WEBSITE, IF YOU'RE INTERESTED, WITH PRESENTATIONS, THE SPEAKERS WHICH WAS QUITE AMAZING GROUP OF PEOPLE AND EXECUTIVE SUMMARY IS ON THE WEBSITE. WE'RE WORKING ON A WHITE PAPER. I HOPE I HAD COMES TO YOU EVENTUALLY. THIS IS DUE DILIGENCE TO FIGURE OUT STATE OF THE SCIENCE AND WHAT WOULD NCATS NEED TO DO IN THIS SPACE. BEFORE THAT WOULD BRING A CONCEPT CLEARANCE TO YOU OF COURSE SO YOU MAY SEE THAT IN THE FUTURE. ANOTHER MEETING THAT MIKE ROSENBLATT AND LIZ STONER AND A NUMBER OF US TALKED ABOUT BEFORE WAS A VERY INTERESTING MEETING, PROVOCATIVELY TITLEED THE ROLE OF NIH IN DRUG DEVELOPMENT AND ITS IMPACT ON PATIENT ACCESS, EVERYTHING BEFORE THE "AND" IS OUR BREAD AND BUTTER, IT'S PART OF OUR MISSION. THE ISSUE, IMPACT ON PATIENT ACCESS, THAT'S CODE FOR, WELL, GOSH, NIH WAS INVOLVED IN SOME OF THE WORK THAT WENT INTO DEVELOPING THIS DRUG OR DEVICE OR THERAPEUTIC SO SHOULD IT HAVE A ROLE IN SETTING THE PRICE OF THAT EVENTUALLY MARKETED THERAPEUTIC. SO A LOT OF DISCUSSION OF MARCH IN, OTHER USES OF PATENT RIGHTS. I WAS HAPPILY INVITED TO GIVE THE OVERVIEW IN THIS SPACE. IT WAS A REALLY INTERESTING MEETING THAT WAS A FOLLOW-UP OF AN IOM REPORT THAT MIKE ROSENBLATT WAS ON, MAKING MEDICINES AFFORDABLE. IT'S WORTH LOOKING AT IF YOU HAVEN'T SEEN IT. AND THIS WAS A FOLLOW-UP OF THAT MEETING. I WOULD SAY THE MEETING STARTED OUT WITH A FAIR AMOUNT OF CONTENTIOUSNESS, BUT I THINK BY THE END THERE WAS REALLY A LOT MORE UNANIMITY THAN I HAD THOUGHT MIGHT COME OUT OF THIS. AND THAT I DARED HOPE. AN APPRECIATION THAT WHAT NIH DOES IS ABSOLUTELY CRITICALLY BUT IS REALISTICALLY A SMALL BUT OFTEN IMPORTANT PART IN THIS VERY COMPLICATED AND DIFFICULT AND MULTI SECTOR PROCESS. I THINK THAT KIND OF -- JUST LACK OF KNOWLEDGE OF HOW THIS PROCESS WORKS IS SOMETHING THAT WE HAVE TALKED ABOUT HERE, WE TALK ABOUT IT AT NCATS ALL THE TIME. BUT IT WAS REALLY IN EVIDENCE AT THAT MEETING. I WAS GLAD WHEN PRESENTED WITH HOW THIS PROCESS WORKS THE ATTENDEES, MOST WERE QUITE OPEN MINDED ABOUT THE FACT THAT WHAT THEY HAD THOUGHT MAY NOT QUITE BE THE RIGHT APPROACH. SO, REALLY QUITE A POSITIVE OUTCOME I THINK FROM MY POINT OF VIEW. I SHOULD JUST MENTION YOU NOTICE THE FIRST SPEAKER AFTER THE BREAK WAS SOMEBODY NAMED JANET WOODCOCK. AND IT WOULD HAVE DELIGHTED YOU TO LISTEN TO THIS BECAUSE JANET AND I DID NOT CORRELATE IN ANY WAY. I DIDN'T KNOW SHE WAS SPEAKING. AND YET HER TALK WAS EXACTLY MY TALK FROM THE PERSPECTIVE OF FDA. IT WAS REALLY A BEAUTIFUL THING TO WATCH. ALL THE SAME ISSUES, ONE FROM RESEARCH PERSPECTIVE, THE OTHER FROM A REGULATORY PERSPECTIVE. AND I THINK REALLY SET THE TONE FOR THE MEETING AND OF -- IN A REALLY POSITIVE WAY. SOMETHING I WANTED TO MENTION TO YOU, I DON'T KNOW IF YOU HEARD THIS TERM, REFERRING TO MANELS, PANELS MADE UP OF ALL MEN. AND SO DR. COLLINS CAME OUT WITH THIS ANNOUNCEMENT BACK IN JUNE THAT HE WAS WITH RARE EXCEPTIONS NOT GOING TO TAKE PART IN MEETINGS THAT DIDN'T HAVE ADEQUATE DIVERSITY AND WE OF COURSE ARE IN COMPLETE AGREEMENT WITH THIS SO I DECIDED I WOULD COME OUT WITH A STATEMENT OF MY OWN TO THIS EFFECT, SUPPORTING DIVERSITY AND INCLUSIVE MEETINGS AND REPRESENTATION ON PANELS FOR ALL THE KINDS OF REASONS THAT YOU CAN IMAGINE, REPRESENTED IN THIS ROOM NOW. WE GO, PER MY COMMENTS A MINUTE AGO ABOUT THE IOM, NATIONAL ACADEMY OF SCIENCE, ENGINEERING AND MEDICINE AS IT'S NOW CALLED, MEETING ON THE ROLE OF NIH IN DRUG DEVELOPMENT, THIS REALLY NEED TO DEFINE OUR FIELD, DEFINE OF FIELD OF TRANSLATIONAL SCIENCE, SO TWO THINGS HAPPENED SINCE THE LAST MEETING WHICH I THINK WILL MOVE US FORWARD HERE. ONE IS A VIDEO WHICH IS REALLY AIMED AT TRAINEES, EXPLAIN IN SIMPLE TERMS WHAT TRANSLATIONAL SCIENCE IS. I'LL GOING TO TRY TO PLAY THIS FOR YOU, IT'S TWO MINUTES LONG AND HOPEFULLY WILL WORK. >> EVERY DAY, SCIENTISTS AROUND THE GLOBE MAKE DISCOVERIES AND BREAK THROUGHS IN ILLNESS, TURNING THEM TO IMPROVEMENTS IN HUMAN HEALTH IS DIFFICULT. THE DRUG DEVELOPMENT JOURNEY COSTS TOO MUCH, TAKES TOO LONG, AND FAILS FAR TOO OFTEN. MEANWHILE, THOUSANDS OF DISEASES AFFECT HUMAN HEALTH BUT TREATMENTS ARE ONLY AVAILABLE FOR ABOUT 500. THIS REPRESENTS A CHALLENGE, BUT ALSO A HUGE OPPORTUNITY. THERE IS TREMENDOUS NEED FOR PEOPLE TO DISCOVER, DEVELOP AND DISSEMINATE THE NEXT GENERATION OF SCIENCE AND TECHNOLOGY TO IMPROVE HUMAN HEALTH. THIS PROCESS IS CALLED TRANSLATION. TRANSLATION IS THE MULTI-STEP PROCESS OF TURNING OBSERVATIONS IN THE LAB, CLINIC AND COMMUNITY INTO INTERVENTIONS THAT IMPROVE LIVES IN DIAGNOSIS, THERAPEUTICS, PROCEDURES, DEVICES AND BEHAVIORAL CHANGES. THE FIELD OF TRANSLATIONAL SCIENCE REQUIRES PEOPLE WITH DIVERSE SKILLS INCLUDING BIOLOGY, CHEMISTRY, COMPUTER SCIENCE, ENGINEERING, MEDICINE, AND PUBLIC HEALTH TO COME TOGETHER AND WORK AS A TEAM, IN ORDER TO MAKE A REAL IMPACT. THE FUNDAMENTAL CHARACTERISTICS NEEDED GO BEYOND INDIVIDUAL SPECIALIZATION. IT INCLUDES A BROAD UNDERSTANDING ACROSS TRANSLATIONAL SPECTRUM AND BE A TEAM PLAYER, RIGOROUS RESEARCHER, SYSTEMS THINKER, DOMAIN EXPERT, PROCESS INNOVATEDDOR AND BOUNDARY CROSSES. THESE ARE EXPLORERS WORKING IN TEAMS, INNOVATIVELY AND COLLABORATIVE, BREAKING DOWN BARRIERS AND IMPROVES LIVES. RECENTLY TRANSLATIONAL PROJECTS HAVE DEVELOPED NEW MEDICAL DEVICES, CREATED GENE THERAPIES FOR RARE DISEASES, BUILT TOOLS THAT SUPPORT PATIENTS AND THEIR ENGAGEMENT IN THE DRUG DEVELOPMENT PROCESS. THESE DATA MINING RESOURCES TO ADVANCE BIOMEDICAL DATA SHARING, REPURPOSED EXISTING MEDICINES TO TREAT OTHER DISEASES, AND ADVANCE DRUG DEVELOPMENT PROCESSES. THE FIELD IS INTRINSICALLY REWARDING. TRANSLATIONAL SCIENCE PRESENTS TREMENDOUS OPPORTUNITY FOR INNOVATION AND SYSTEMATIC CHANGE. DEVELOPING SOLUTIONS THAT MAKE THE PROCESS OF DEVELOPING A NEW MEDICINE BETTER, FASTER, AND MORE EFFICIENT. TRANSLATIONAL SCIENCE IS THE YOUNGEST SCIENCE WITH BOUNDLESS PROMISE TO TRANSFORM BIOMEDICAL RESEARCH IN MEDICINE. IT REQUIRES INNOVATIVE THINKERS WITH A PATIENT-FOCUSED APPROACH TO ENSURE THAT THE PATIENT'S PERSPECTIVE IS INCLUDED IN EVERY STEP OF THE RESEARCH PROCESS. BREAKING DOWN BARRIERS ANDS COLLABORATING TO PREVENT, TREAT AND CURE DISEASE. IF YOU WANT TO MAKE A REAL IMPACT ON THE LIVES OF MILLIONS, LEARN MORE ABOUT THE FIELD OR BECOME A TRANSLATIONAL SCIENTIST, PLEASE VISIT US ONLINE. JOIN US. >> I THANK CHRISTINE AND THE OFFICE, ONE OF MY SENIOR ADVISORS. THERE SHE IS. SHE WAS THE DRIVING FORCE BEHIND THIS. I THINK YOU'LL AGREE IT CAME OUT EXTREMELY WELL. THANK YOU FOR THAT. AND IN PARALLEL, WE WERE WORKING ON A PUBLICATION WHICH CAME OUT OF A GROUP THAT WE HELPED CO-FOUND A NUMBER OF YEARS AGO, TRANSLATION TOGETHER. THIS IS A GLOBAL GROUP, PEOPLE FROM THESE INSTITUTIONS, THERAPEUTIC INNOVATION IN AUSTRALIA, CANADA, EUROPE AND US, THIS IS A PRE-CLINICAL SPACE MAINLY, AND THIS IS WHERE THOSE DEFINITIONS OF TRANSLATIONAL SCIENCE, SCIENTISTS, ARE CODIFIED IN THE SCIENTIFIC LITERATURE. PROBABLY WON'T BE A SURPRISE TO ANY OF US BUT WHEN WE GOT TOGETHER WITH THESE GROUPS WE FOUND THE ISSUES IN TRANSLATION REALLY ARE THE SAME, DOESN'T MATTER WHERE YOU ARE IN THE WORLD. ALL OF THE SCIENTIFIC CULTURAL, SOCIAL ISSUES, MISUNDERSTANDSS S ARE JUST AS MUCH THE CASE IN CANADA AND EUROPE AS HERE. I GOT E-MAILS, THANK YOU FOUR PUBLISHING THIS BALLS YOU DESCRIBED WHAT I AM, PEOPLE IN THEIR 60s WHO NEVER HAD AN IDENTITY IDENTITY BECAUSE THEY DON'T FIT. WE'RE EXCITED ABOUT THIS, SOMETHING WHICH WE HOPE WILL MOVE THE FIELD FORWARD IN DEFINING OUR FIELD. OKAY. SO NOW I'M GOING TO JUMP TO PRE-CLINICAL INNOVATION, RUN BY ANTON SIMEONOV. A COUPLE EXAMPLES OF THE KIND OF WORK THIS GROUP DOES. THEY ARE EXAMPLES BUT I THOUGHT YOU WOULD FIND THEM INTERESTING. THIS ONE CAME OUT OF JIM'S GROUP, CHEMICAL PROBE DEVELOPMENT FOR NOVEL TARGETS. THE OPPONENT HERE IS NOVEL TARGET, NO CHEMICAL MATTER TO MANIPULATE, HOW CAN YOU FIGURE OUT ITS ROLE IN DISEASE, YOU CAN'T DO PHARMACOLOGY BECAUSE YOU HAVE MOLECULAR GENETIC TOOLS. THIS HAS TO DO WITH AN ITCH SIGNALING PATHWAY THAT IS MEDIATED BY ONE OF THE TRIP CHANNELS, QUITE FAMOUS IN THE PAIN FIELD. THIS TRPV1 CHANNEL IS ACTIVATED BY A PEPTIDE, AND IT'S EXPRESSED AS YOU MIGHT EXPECT IN THE DORSAL ROOT GANGLIA, IT'S A G-PROTEIN COUPLED RECEPTOR. THIS WENT THROUGH SOME OF THE USUAL PROCESSES THAT ALL OF US KNOW AND LOVE, QUANTITATIVE HIGH-THROUGHPUT SCREENING, TITRATION-BASED, CONCENTRATION-BASED SCREENING DEVELOPED AT NCATS A NUMBER OF YEARS AGO. AND SCREENING A LARGE COMPOUND LIBRARY COMING UP WITH A NUMBER OF COMPOUNDS WHICH HAVE APPROPRIATE PHARMACOLOGY RIGHT OUT OF THE PRIMARY SCREEN, AND THAT'S WHAT YOU'RE LOOKING AT, ON THE BOTTOM RIGHT IS A NUMBER OF COMPOUNDS ON THE BOTTOM, REDUCTION OF ACTIVITY ON THE TOP. WHAT THE SLOPE LOOK LIKE, DOSE-RESPONSE CURVES, THIS WENT THROUGH A LOT OF MED CHEM OPTIMIZATION, TO OPTIMIZE FOR HAVING THE SUITABLE PK PROPERTIES FOR IN VIVO STUDIES, AND THEN THAT WAS DONE BY OUR COLLABORATORS WHO IN THIS CASE ARE IN OTHER INSTITUTE, AND REDUCED SCRATCHING RESPONSES BY MORE THAN HALF, TO HISTAMINE, AND WE WERE WORKING ON A SECOND AGENT THAT WORKS VIA DIFFERENT MECHANISM. SO THIS RESULTED IN A HIGH PROFILE PUBLICATION. YOU MIGHT FIND IT CURIOUS THAT THIS WAS DONE WITH INVESTIGATORS AT THE NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH BECAUSE TEETH DON'T ITCH, AS YOU MIGHT KNOW. A A NEUROLOGIST I USED TO ASK PEOPLE. IF THEY HAVE POSITIVE REVIEW OF SYSTEMS IF YOU ASK IF THEIR TEETH ITCH AND THEY SAY YES YOU KNOW THERE'S SOMETHING GOING ON. BUT NONETHELESS THOSE WERE OUR COLLABORATORS HERE. IT'S A GREAT EXAMPLE OF DEVELOPING A WHOLE -- POTENTIALLY A WHOLE NEW THERAPEUTIC FIELD VIA THE KIND OF COLLABORATION THAT N CATS DOES. I WANT TO TELL YOU BRIEFLY ABOUT GOING FROM 2D SCREENING TO 3D SCREENING. YOU'VE SEEN ME SHOW THIS SLIDE BEFORE THAT WE LOVE 2D SCREENING, I SHOWED YOU AN EXAMPLE, 2D CELLS, WE'RE ASKING WITH ADVENT OF 3D PRINTING AND iPS CELLS AND OTHER IMAGING TECHNOLOGIES WOULD IT BE POSSIBLE TO DEVELOP 3D TISSUE MODELS THAT ARE MORE PREDICTIVE OF DRUG OUTCOME IN THE CLINIC AND DO SCREENING BASED ON THOSE, NOT FOR REGENERATIVE MEDICINE, ARE THEY BETTER THAN 2D MODELS OR NOT AND WHAT IS THE MINIMUM TISSUE COMPLEXITY. DO YOU NEED A SPHEROID OR ORGANOID, PRINT OR DO A TISSUE CHIP, THAT'S SOMETHING WE'RE WORKING ON. THE IDEA HERE IS THAT WE WOULD NOT DO CONVENTIONAL HIGH-THROUGHPUT SCREENING OF HUNDREDS OF THOUSANDS OF COMPOUNDS ON THESE, BUT RATHER THESE WOULD BE SECONDARY OR ORTHOGONAL SCREENS IN TISSUE MODELS BEFORE WE GO INTO WHAT IS CURRENTLY A MOUSE, BUT WE HOPE BEFORE LONG WILL BE ONE OF THESE REPLACING THE MOUSE, A TISSUE CHIP. AND SO THIS IS -- WE HAVE A WHOLE GROUP IN THE DIVISION OF PRE-CLINICAL INNOVATION FOCUSED ON TECHNOLOGIES FOR TISSUE BIOFABRICATION FOR DISEASE MODELING AND DRUG SCREENING, NOTICE AGAIN THIS IS NOT REGENERATIVE MEDICINE. THE PROBLEMS THAT WE'VE RUN INTO AMONG THEM ARE REALLY MAJOR PROBLEMS WITH CELL SOURCING. AS SOON AS YOU START DOING 3D INSTEAD OF 2D, THE NUMBER OF CELLS OF COURSE GOES UP EXPONENTIALLY. HOW DO YOU MAKE THOSE AND MAKE THOSE IN QUALITY AND QUANTITY THAT YOU NEED AND BIOFABRICATE THESE THINGS? THE NUMBER OF POTENTIAL STRUCTURES AND SCAFFOLDS AND EXTRACELLULAR MATRIX IS ALMOST LIMITLESS, SO-CALLED BIOINK, HOW DO YOU QUALIFY FOR USE AND SHOW OF LIKE HAPPENS IN THE TISSUE CHIP PROGRAM, HOW DO YOU GET AN IDEA THAT THIS ACTUALLY IS REPRESENTING THE IN VIVO SITUATION THE WAY YOU WANT IT TO. THESE HAVE TO BE IF NOT HTS COMPATIBLE BUT AT LEAST MTS COMPATIBLE, MAYBE 96 OR 84 WELL PLATE COMPATIBLE. OF COURSE IMAGINE DOING IMAGING ON A 3D STRUCTURE, BECOMES TREMENDOUSLY MORE DIFFICULT, BUT ALSO PERHAPS MORE ILLUMINATING. AND WHAT DO DO YOU WITH THE GOD& AWFUL AMOUNT OF DATA YOU GENERATE WITH THIS KIND OF TECHNOLOGY? AND JUST ONE EXAMPLE WHICH I THOUGHT I WOULD PUT IN HERE, CORRELATED WITH THE ITCH EXAMPLE, I JUST SHOWED YOU, THEY HAD NOTHING TO DO WITH EACH OTHER, THIS IS AN ITCHING DISEASE, ATOPIC DERMATITIS, AND COULD WE DEVELOP A VASCULARIZED SKIN EQUIVALENT MODEL, A.D., DONE WITH COLLABORATEDDORS INSIDE AND OUTSIDE NIH WHO HAVE EXPERIENCE IN SKIN AND THIS SIMPLY IS SHOWING YOU WE'RE ABLE TO GENERATE WHAT LOOKS LIKE A QUITE TRUE TO FORM VASCULARIZED SKIN EQUIVALENT, VSE, BUT THEN WHEN WE -- USING CYTOKINE TREATMENT INDUCE AN A.D. MODEL THAT'S NOT ALZHEIMER'S DISEASE, IT'S ATOPIC DERMATITIS, AND THE TIER ON THE BOTTOM IS THE BARRIER FUNCTION THE SKIN NORMALLY PROVIDES FOR US, NORMALLY IT HAS GOOD BARRIER FUNCTION BUT AS IS THE CASE IN ECZEMA OR ANOTHER WORD FOR ATOPIC DERMATITIS THE BARRIER FUNCTION IS REDUCED, YOU SEE THAT IN THESE MODELS. AND COULD YOU RESCUE THIS USING AN EXPERIMENTAL AGENT, IN THIS CASE JAK INHIBITOR, KINASE INHIBITOR, BEING STUDIED FOR ATOPIC DERMATITIS AND IN FACT ONE CAN RESTORE TO A GREAT DEGREE THE BARRIER FUNCTION AND CHANGE THE -- SOME OF THE MARKERS THAT ARE CHARACTERISTICS OF THIS PROCESS AS WELL. AND WHAT I WANT YOU TO LOOK AT, WHAT WE'RE COMPARING ON THE RIGHT SIDE, IF YOU HAD 2D KERATINOCYTES OR JUST EPIDERMIS THAT'S NOT VASCULARIZED YOU DON'T SEE THIS. IT HAS TO BE A COMPLEX TISSUE, WHICH HAS MULTIPLE CELL TYPES AND IS VASCULARIZED TO PHENOCOPY THE DISEASE PHENOTYPE. SO IT'S AN EXAMPLE OF KIND OF POTENTIAL THAT WE THINK HAD THIS TECHNOLOGY HAS FOR DOING SCREENING, PRIMARY SCREENING WITH A SMALL NUMBER OF COMPOUNDS PERHAPS FOR REPURPOSING OR ORTHOGONAL SCREENING AFTER TRUE HTS. THIS IS PUBLISHED, IT'S A COLLABORATION, THE ONLY REASON THIS IS POSSIBLE. YOU MIGHT WONDER WHY ARE PEOPLE AT THE EYE INSTITUTE WORKING ON SKIN? THAT'S A LONGER STORY BUT THEY WERE SOME OF OUR COLLABORATORS AS WELL AS DEPARTMENT OF BIOENGINEERING AT LEHIGH IN PENNSYLVANIA. ONE LAST STORY FROM THE PRE-CLINICAL INNOVATION IS FROM THE TRUE DRUG DEVELOPMENT PART. THIS IS LEAD TO IND IN DRUG DEVELOPMENT VERNACULAR. THIS PROJECT WE TOOK ON BOTH BECAUSE OF THE DISEASE NEED, BUT ALSO BECAUSE IT ADDRESSES ONE OF THE SYSTEMATIC ISSUES THAT WE HAD TALKED ABOUT IN THIS COUNCIL, CAN BOARD, THE PROBLEM OF REPURPOSING THERAPEUTICS WHICH SEEMS QUITE STRAIGHTFORWARD BUT IN PRACTICE IS ANYTHING BUT. SO THIS IS A POTENTIAL THERAPEUTIC FOR HEMOGLOBINOPATHY, SICKLE CELL AND THALASSEMIA, YOU KNOW THERE ARE TREATMENTS FOR THESE BUT THEY ARE PROBLEMATIC AT BEST FOR A VARIETY OF REASONS. AND THERE ARE GENE THERAPY STRATEGIES IN DEVELOPMENT BUT ONE OF THE THINGS EVERYBODY WHO DOES THIS IS REALIZE MOST PEOPLE AFFECTED WORLDWIDE WILL REALISTICALLY AT LEAST IN OUR LIFETIMES NOT HAVE ACCESS TO THESE VERY EXPENSIVE AND CUMBERSOME TECHNOLOGIES, GENE THERAPY. SMALL MOLECULE TREATMENT WOULD HAVE A TREMENDOUS ADVANTAGE IN MANY WAYS. AND SO WHAT MANY PEOPLE TRIED TO DO FOR A LONG TIME IS TO INCREASE THE PHENOHEMOGLOBIN, INCREASE GAMMAGLOBIN GENE EXPRESSION THAT'S NORMALLY EXPRESSED IN THE FETUS, AND DECREASED AFTER BIRTH WHEN BETA-GLOBIN EXPRESSION IS INCREASED. SO THE QUESTION IS COULD YOU START UP GAMMAGLOBIN, FETAL HEMOGLOBIN SYNTHESIS AGAIN BECAUSE THAT FORM OF HEMOGLBIN IS NOT SUSCEPTIBLE TO THE KIND OF DEFECTS THAT YOU HAVE IN THE HEMOGLOBINOPATHIES. SO WHAT IS THIS COMPOUND? IT'S BENZORACIDE, I NEVER HEARDED OF THE DOPAMINE CARBADOXYLACE INHIBITOR, TO PREVENT CONVERSION OF THE DOPA IN THE PERIPHERY, WHICH CAUSES SIDE EFFECTS, BENZORACIDE IS A DIFFERENT STRUCTURE, APPROVED IN EUROPE, NOT HERE. THE HIGH-THROUGHPUT SCREEN OUR COLLABORATORS SUSAN AT B U, IDENTIFIED THIS COMPOUND ON THE UPPER RIGHT, BUT THE PROBLEM WAS IT'S ONLY APPROVED TO TREAT PARKINSON'S DISEASE, ONLY APPROVED IN COMBINATION WITH DOPA. NOT AS A SINGLE AGENT. SO, WE NEEDED TO REFORM LATE AS SINGLE AGENT, APPROVED A LONG TIME AGO, SOMETHING WE'VE RUN INTO ALL THE TIME, IT'S A VERY OLD DRUG, OFT PATENT FOR AGES BUT PRE-CLINICAL DATA OR EMA IS REALLY OLD. SO THE REQUIREMENTS FOR APPROVAL IN THE DRUG MASTER FILE EVEN IF WE COULD GET IT ARE INADEQUATE FOR APPROVAL NOW. AND SO REGULATORY STUDIES WOULD BE NEEDED AND THIS IS ACTUALLY -- WE NEED TO FIGURE OUT WHETHER IT'S BOTH OR ONE OTHER THE OTHER, WHICH ONE ARE WE GOING TO APPROVE. SO, THIS IS RARE NEGLECTED DISEASE TEAMED UP WITH FOLKS AT B U, BOTH ISOMERS WERE AFFECTED, REFORMULATED AS SINGLE PRODUCT, INDEPENDENT OF L-DOPA AND GENERATED THE DATA THAT WAS REQUIRED WITH THOSE DATA, AN IND WAS SUBMITTED TO FDA AND HEALTH CANADA, AND CLEARED BY BOTH AND SO THE SMALL COMPANY WHICH SUSAN AND HER COLLEAGUES STARTED IS GOING TO INITIATE A PHASE 1B TRIAL IN BETA THALASSEMIA, A GREAT STORY WITH POTENTIAL LARGE PUBLIC HEALTH IMPACT BUT SOMETHING THAT ALMOST CERTAINLY WOULD NOT HAVE HAPPENED WITHOUT OUR COLLABORATION AND SOMETHING THAT'S TAUGHT US A LOT ABOUT HOW TO HANDLE SOME OF THE PROBLEMS, SOME OF THE MANY PROBLEMS IN THE REPURPOSING SPACE. OKAY. SO NOW I'M GOING TO MOVE TO THE "CAN" PROJECTS. YOU'LL HEAR ABOUT SOME OF THIS LATER IN THE CURES ACCELERATION NETWORK REVIEW BOARD UPDATE THAT LYNN AND RON AND OTHERS WILL DO. BUT THESE ARE SOME OF THE CURRENT PROJECTS OR PROJECTS WE'VE HEARD ABOUT BEFORE. MPS, YOU MAY REMEMBER, MICROPHYSIOLOGICAL SYSTEMS, THAT'S ANOTHER WORD FOR A TISSUE CHIP, AND THIS PROJECT HAS BEEN GOING ON SINCE 2012, AND SO IT'S REALLY AT THE STAGE, WE'LL TALK ABOUT THIS LATER, IT'S REALLY THE STAGE OF TRANSITIONING OUT. NCATS HAS DONE ITS JOB CATALYZING THIS FIELD, DAN TAGLE IS ALMOST SINGLE-HANDEDLY RESPONSIBLE FOR MAKING IT HAPPEN. HAD GOOD HELP BUT IT'S AN NCATS PRODUCT AND WE'RE PROUD OF THAT. DAN AND LUCY AND THE TEAM FROM THE VERY BEGINNING HAVE BROUGHT IN OTHER PARTNERS, BOTH PUBLIC PARTNERS, PRIVATE PARTNERS, FDA, ET CETERA, AND SO THIS IS A GREAT EXAMPLE OF OTHER INSTITUTES AND CENTERS AT NIH, THERE'S THE FRUIT SALAD OF ACRONYMS AGAIN. OTHER INSTITUTES AT NIH RESPONSIBLE FOR DIFFERENT DISEASES OR ORGAN SYSTEMS WHO HAVE NOW PICKED UP THIS TECHNOLOGY AND ARE FUNDING ON THEMSELVES OTHER COUNTRIES DOING THE SAME THING, AND ASIA, EUROPE, AUSTRALIA, OTHER AGENCIES OF THE FEDERAL GOVERNMENT INCLUDING BARDA, CDC, EPA, ET CETERA, ARE WORKING ON THIS TECHNOLOGY AS WELL, AND AS I THINK I MENTIONED TO YOU BEFORE, THROUGH MY WORK AS LIAISON TO NASA, OTHER HHS AGENCIES, NASA AND OTHER NON-HHS AGENCIES HAVE GOTTEN INTERESTED. IT'S A GREAT STORY. WE TALK ABOUT DEVELOPING, DEMONSTRATING, DISSEMINATING. THIS SHOWS YOU THE BIG BANG DISSEMINATION GOING ON WITH THIS PROJECT THAT HAS REALLY BEEN VERY SUCCESSFUL. WE'VE TALKED ABOUT CHIPS IN SPACE. SO AN UPDATE HERE, THAT'S THE ROCKET BUILDING DOWN AT KENNEDY SPACE CENTER WHERE THE SATURN 5 ROCKETS CAME OUT OF, A CANONICAL BUILDING. I THINK YOU MAY REMEMBER THAT -- UH-OH. THERE'S ANOTHER PIECE OF THE SLIDE NOT SHOWING UP. THE LAST MEETING I TOLD YOU THERE WAS A SECOND LAUNCH OF TISSUE CHIPS THAT HAPPENED IN MAY, AND THOSE SAMPLES HAVE NOW COME BACK AND ARE BEING ANALYZED FOR OMICS MARKERS, HISTOLOGICAL MARKERS. WE LEARNED A LOT IN TERMS OF SCIENCE AND TECHNOLOGY AND THESE FLIGHTS WERE TO VALIDATE THE TECHNOLOGY IN MICROGRAVITY BUT NOT TEST COMPOUNDS FOR AFFECTING THOSE PHYSIOLOGIES ON THESE FLIGHTS. THAT'S GOING TO BE FOR THE REFLIGHT WHICH WILL HAPPEN NEXT YEAR OR THE YEAR AFTER FOR EACH OF THESE PLATFOMS, EACH OF THE DIFFERENT TISSUE CHIP PLATFORMS. ALSO IN THE NASA WORLD, I WAS PRIVILEGED TO DO A PANEL WITH SANJAY GUPTA AND A FORMER ASTRONAUT, CHANCELLOR, WHO YOU CAN PROBABLY PICK OUT WHICH ONE SHE IS, GIVEN THE OUTFIT THERE, AND THAT WAS REALLY QUITE A WONDERFUL SESSION AT THE INTERNATIONAL SPACE STATION R&D CONFERENCE, AND THIS IS US ON THE STAGE. I JUST WANT YOU TO NOTICE I'M PLAYING ALL THE ANGLES HERE TRYING TO BRING PEOPLE INTO THE SCIENCE HERE. I WANT YOU TO LOOK AT WHAT I HAD TO BE WEARING THERE, YES, THOSE ARE SPACE STATION SOCKS THAT I WORE TO THIS MEETING, AND SANJAY HAD PLANET SOCKS BECAUSE HE THOUGHT HE WAS GOING TO BE A COOL GUY TO WEAR PLANETS TO THE CONFERENCE AND I SMOKED HIM BALLS I HAD SPACE STATION SOCKS THAT BLEW HIS PLANET SOCKS OUT OF THE WORD. GLAD WE'VE SETTLED THAT SCORE. IT WAS A GREAT MEETING. AS NASA LIAISON, LUCY LOWE, WHO IS HELPING ME ON THIS, AND DAN RAN THE STATE OF THE SCIENCE MEETING LAST YEAR WITH NASA ON THIS TECHNOLOGY. THAT WAS A LOT OF PROGRAMMATIC FOLLOW-UP, ATTENDANCE BY MULTIPLE OTHER AGENCIES AND NIH INSTITUTES, MUST BE ORGANIZATIONS, EXTERNAL ORGANIZATIONS, EXPLORING OBLIGATION OF FUNDS, THAT MEANS GRANTS, FOR AGENCY SPECIFIC NPS PROGRAMS, AND WE'RE ANTICIPATING INCREASING INTEREST FROM THESE AND OTHER GOVERNMENT AGENCIES ALLOWING US TO OFFLOAD THIS NOW TO OUR PARTNERS WHILE WE MOVE ON TO NEW OTHER TECHNOLOGIES. OKAY. RARE DISEASES RESEARCH. I'M NOT GOING TO SAY ANYTHING ABOUT THIS BECAUSE ANN IS GOING TO TELL YOU EVERYTHING IN THE AFTERNOON. SO STAY TUNED FOR THAT. SO, LESLIE, DCI, DIVISION OF CLINICAL INNOVATION, LASTLY, I WANT TO REMIND YOU THIS PROGRAM SO LARGE AND COMPLICATED, HOW DO YOU THINK ABOUT THIS PROGRAM? WELL, AT A GLANCE, THE BIGGEST PART, WHAT WE CALL HUBS, THESE ARE MULTIPLE MECHANISM AWARDS TO ACADEMIC MEDICAL INSTITUTIONS, AND THOSE ARE -- THOSE HAVE A NUMBER OF TRAINING COMPONENTS, AT LEAST WHAT WE CALL A KL2, A POSTDOCTORAL EARLY CAREER INVESTIGATOR PROGRAM, AND OPTIONAL PRE-DOCTORAL PROGRAM, TL1, THOSE ARE THE REQUIRED COMPONENTS, ACADEMIC CENTER GRANT AND KL2, OPTIONAL TL1, THE HUBS, BRINGING THEM TOGETHER TO COLLABORATE WITH EACH OTHER AND LEARN FROM EACH OTHER AND DO PROJECTS WE LIKE TO THINK ABOUT AS THE MORTAR HOLDING THE BRICKS TOGETHER TO MAKE A REALLY FUNCTIONAL WALL, THESE ARE PROJECTS THAT REQUIRE TWO OR THREE CTSAs TO WORK TOGETHER, HUBS TO WORK TOGETHER TO SOLVE A PROBLEM NONE OF THEM CAN DO BY THEMSELVES. SUPPLEMENTS TO DISSEMINATE A DEVELOPMENT AT ONE CTSA WHICH COULD BE INSTANTIATEED IN THE OTHER. VIRTUALLY EVERY PROBLEM YOU CAN IMAGINE HAS EXPERTISE IN ONE OR ANOTHER OF THESE INSTITUTIONS. BUT NOT AT ALL. RATHER THAN ALL THE INSTITUTIONS HAVING TO DRUM UP THIS TECHNOLOGY OR THIS EXPERTISE, IT CAN BE DEVELOPED IN ONE PLACE, DISSEMINATED TO ANOTHER, THAT'S A HUGE WIN AT VERY LOW COST. SO THAT'S WHY WE'RE VERY EXCITED ABOUT THESE KINDS OF SUPPLEMENTS, IT'S WORKED VERY WELL. WE DO HAVE PARTICULAR INTEREST AREAS THAT COME AND GO, TWO OF THE CURRENT ONES ARE OPIOIDS AND RURAL HEALTH. WE HAVE DIVERSITY SUPPLEMENTS FOR INCREASING DIVERSITY IN THE WORKFORCE AND HELPING CAREER REENTRY, FOLKS OUT OF THE FIELD FOR ONE REASON OR ANOTHER AND COMING BACK INTO THE CENTER FIELD. AND THOSE ARE INTERHUB COLLABORATIVE OPPORTUNITIES, TWO, THREE, FOUR, FIVE HUBS, AND THERE'S SOME THAT GO ACROSS THE CONSORTIUM, AND THOSE ARE A CORE DATA CENTER, CALLED CLICK, THE INFORMATICS PIECE OF THIS, CENTER FOR DATA TO HEALTH WHICH KEN WILL TALK ABOUT THEY END OF THE DAY TODAY AND TRIAL INNOVATION NETWORK WHICH WE'VE TALKED ABOUT HERE BEFORE AND I'LL MENTION AGAIN JUST IN A SECOND. SO THAT'S WHAT THE PROGRAM LOOKS LIKE. SO IF YOU HEAR ABOUT CLIC OR DISSEMINATION OR A HUB THAT'S WHAT WE'RE TALKING ABOUT. FY19 THESE WERE THE AWARDS THAT GOT MADE. MOST HAD BEEN HUBS BEFORE, THE ONES IN WHITE. THERE ARE TWO OF THEM THAT WERE NEW, UNIVERSITY OF VIRGINIA AND RUTGERS ARE NEW HUBS FOR THE FIRST TIME INTO THE FAMILY THIS YEAR. AND I JUST WANT TO CALL OUT THE ONE AT UNIVERSITY OF ARKANSAS, THIS IS AN IDEA STATE, IDEA IS AN NIH PROGRAM, INSTITUTIONAL DEVELOPMENT AWARD, THIS IS FOR STATES WHICH HAVE A RELATIVELY LOW AMOUNT OF NIH GRANT SUPPORT. AND THEY TEND TO BE IN THE MIDDLE OF THE COUNTRY, NOT ALL. AND THEY HAVE BECOME DOUBLY IMPORTANT IN THE ERA OF EMPHASIS ON RURAL HEALTH, AND THE OPIOID CRISIS, WHICH IS DIFFERENTIALLY AFFECTED THESE STATES. WE HAVE, MIKE AND HIS STAFF, REALLY HAVE BEEN DRIVING A CLOSER RELATIONSHIP BETWEEN THE IDEA STATE PROGRAMS WHICH ALSO HAVE SOME CLINICAL TRANSLATIONAL COMPONENTS TO THEM, AND THE CTSA PROGRAM, SO ARKANSAS IS ONE OF THOSE. I JUST WANT TO MENTION A FEW OF THESE ENHANCING NETWORK CAPACITY AWARDS. AGAIN, I DON'T NEED YOU TO -- DON'T FOCUS ON THE DETAILS HERE, I WANT TO GET YOU A SENSE THESE ARE ALL OVER THE COUNTRY. THEY INVOLVE PARTNERED CTSAs WHICH ARE NOT NECESSARILY NEXT TO EACH OTHER, SO YOU'LL NOTICE THAT UNIVERSITY OF IOWA, BIRMINGHAM AND MINNESOTA ARE -- EVEN IF YOU'RE NOT RICK KNTZ, YOU CAN TELL US THOSE ARE NOT NEXT DOOR TO EACH OTHER. THERE HAVE ALWAYS BEEN LOCAL, REGIONAL COLLABORATIVES, BUT IT HAD BEEN IMPOSSIBLE FOR PEOPLE TO LEARN FROM ORGANIZATIONS WHICH ARE VERY DIFFERENT FROM THEM, AND THEREFORE PROBABLY HAVE STRIKES DIFFERENT FROM THEM, WHEN THE GREATEST THINGS HAPPEN OF COURSE. WHAT I PUT IN RED IS WHAT THE FOCUS IS. HOW DO YOU ENGAGE PATIENTS IN RULE COMMUNITIES, HOW DO YOU DO COMMUNITY ENGAGEMENT REVIEWER TRAINING, HOW DO YOU -- THERE'S A LOT OF COMMUNITY ENGAGEMENT HERE FOR REASONS YOU CAN IMAGINE, WORKFORCE DEVELOPMENT, OPIOIDS, HEALTH DISPARITIES, TAKING AN INTERVENTION WHICH HAS BEEN SHOWN TO BE OF USE FOR ONE PLACE AND INSTANTIATING IN ANOTHER. WE HAVE AWARDS BROKEN OUT HERE BY SOME OF OUR STRATEGIC GOALS, THE WORKFORCE, SPECIAL POPULATIONS, METHODS AND PROCESS, INFORMATICS, TO GIVE YOU A FLAVOR OF WHAT -- SORRY, WHAT SOME OF THESE LOOK LIKE, ALSO COLORED BY THE SPECIAL EMPHASES THAT I MENTIONED BEFORE, OPIOIDS AND RURAL HEALTH. A NUMBER OF THESE HAVE BEEN QUITE GRATIFYING, PARTICULARLY HAVING TO DO WITH THE OPIOID PROCESS, OPIOID EPIDEMIC AND INTERVENTIONS TO WORK. THERE ANOTHER BIT OF GOOD NEWS WE'VE HAD IN THE LAST COUPLE OF WEEKS IS -- COUPLE MONTHS, RATHER, IS SOME DEVELOPMENTS IN AN EFFORT WE'VE BEEN GOING FOR QUITE SOME TIME. WE THINK WE'RE PRETTY SPECIAL AROUND HERE, AND WE THINK THAT OUR TRAINING PROGRAMS ARE PRETTY SPECIAL. BUT OUR SISTER I.C.s, WE THINK, COULD REALLY BENEFIT FROM THE KIND OF TRAINING PROGRAMS THAT WE PUT TOGETHER. AND NOW THE FIRST TWO OF THEM HAVE AGREED AND PUT THEIR MORE THAN WHERE THEIR MOUTH IS SO BOTH NCCIH AND NABIB ARE SUPPORTING SCHOLARS THROUGH THE OUR KL2 PROBLEM, OTHER INSTITUTES WILL BE ABLE TO TAKE ADVANTAGE OF OUR EXPERTISE LIKE WHAT I SHOWED YOU FOR THE TISSUE CHIP PROGRAMS, DISSEMINATING THIS TECHNOLOGIES AND APPROACHES WE'VE DEVELOPED. LASTLY, SOMETHING THAT I HOPE ALL OF YOU WILL CONSIDER CONTRIBUTING DO IS A PROGRAM FEEDBACK CAMPAIGN. THIS IS ALL IN PREPARATION FOR THE NEW FUNDING ANNOUNCEMENT THAT IS RFA REQUEST FOR APPLICATIONS THAT'S GOING TO COME OUT IN A COUPLE YEARS, AND WE'RE LOOKING AT SOME -- POTENTIALLY FAIRLY MAJOR RENOVATIONS TO THE PROCESS, THIS FIELD IS MOVING EXTREMELY RAPIDLY, SO IT WOULD BE WE THINK MALPRACTICE ON OUR PART IF WE JUST STOOD ON OUR LAURELS, WONDERFUL AS THE PROGRAM IS, WE'RE NOT GOING TO TAKE ADVANTAGE OF THE OPPORTUNITIES AND NEEDS THAT NOW EXIST IF WE JUST KEEP DOING WHAT WE'VE ALWAYS DONE. SO, WE'RE INTERESTED IN SOLICITING INPUT ON WHAT THE OBJECTIVES SHOULD BE, HOW DOES THE PROGRAM WORK, WHAT SHOULD OUTCOMES BE, AND SOME SORT OF INSIDE BASEBALL ISSUES ABOUT THE PARTICULARS OF THE RFA FOR PEOPLE WHO KNOW SOCK ABOUT THAT FROM THE TRANSLATIONAL COMMUNITY, CURRENT AND FORMER GRANTEES, PEOPLE WHO HAVE BEEN PEER REVIEWERS OF THE PROGRAM, AND NCATS STAFF. THERE'S THE WAY THE FEDERAL GOVERNMENT DOES THIS, THE ONLY WAY IT CAN DO IT, IS VIA AN RFI, REQUEST FOR INFORMATION, AND THAT IS OPEN LESS THAN A WEEK AGO, OPEN TILL LATE OCTOBER 2019, AND THEN MIKE AND HIS COLLEAGUES ARE GOING TO DO A TOWN HALL Q&A IN JANUARY OF THIS YEAR. AND THIS IS REALLY -- THIS IS THE OFFICIAL LANGUAGE SEEKING INPUT FROM STAKEHOLDER COMMUNITIES AND HOW THE PROGRAM CAN BE STRENGTHENED TO DELIVER ON ITS PROMISE, DEVELOP, DEMONSTRATE, INNOVATIVE APPROACHES, METHODOLOGIES, INTERVENTIONS THAT TRANSLATE INTO HUMAN HEALTH. WE'RE INTERESTED IN YOUR THOUGHTS WHAT WE CAN AND SHOULD DO DIFFERENTLY. THESE ARE AREAS OF CONTENT, ALL THE KINDS OF THINGS THAT YOU WOULD IMAGINE, BARRIERS, COLLABORATION, BRINGING RESEARCH TO BETTER HEALTH AND LOCAL COMMUNITIES, ET CETERA. AND HOW TO MEASURE THE IMPACT. SO I HOPE YOU'LL HAVE A LOOK AT ALL THESE ON THE WEBSITE, THERE IS OF COURSE A WEBSITE WHICH I HOPE YOU WILL GO TO. YOU CAN JUST GOOGLE CTSA, NCATS, RFI, YOU'LL LIKELY FIND IT. AND ALL OF THE COMMENTS HAVE TO BE SUBMITTED ONLINE TO THIS URL. YOU'LL HAVE THE SLIDES OF COURSE, AND WE WOULD REALLY ENCOURAGE YOU TO RESPOND TO IT. IT'S OPEN UNTIL OCTOBER 25th OF NEXT YEAR. AND IF YOU CAN'T REMEMBER THIS, GO TO THE CTSA WEB PAGE ON OUR SITE, IT WILL DIRECT YOU TO THE RFI SITE. AND OF COURSE IF YOU HAVE QUESTIONS, YOU CAN CALL US, WRITE US, E-MAIL US, TWITTER US, OR GO OUT AND FIND A STAMP AND SEND US A LETTER. WE STILL DO GET THOSE OCCASIONALLY. WE'RE GLAD TO GET THOSE AS WELL. OKAY. SO LASTLY, HEAL . WHERE ARE WE WITH HEAL ? TO REMIND YOU, THIS IS WHAT THE UNIVERSE OF HEAL IS. IT'S APPROXIMATELY HALF PAIN MANAGEMENT, WHICH IN LARGE DEGREE GOT US INTO THE PROBLEM TO BEGIN WITH, PARTIALLY, OR ABOUT HALF, IMPROVING TREATMENTSES FOR MISUSE OF OPIOID MISUSE AND ADDICTION, AND NCATS IS INVOLVED IN THREE PARTS OF THIS, BOTH OF THEM IN PAIN, AND EXPANDING THERAPEUTIC OPTIONS FOR ADDICTION AS WELL AS PAIN. SO-- OH, BOY, THIS IS WEIRD. THESE SLIDES ARE AGAIN MISSING THE TITLES BUT ANYWAY THIS IS THE CLINICAL PART. THIS IS THE PAIN EFFECTIVENESS RESEARCH NETWORK. THE IDEA HERE IS THAT PRACTITIONERS WHO HAVE PATIENTS WITH PAIN HAVE VERY LIMITED DATA ON HOW TO HANDLE THAT PAIN FOR THEIR PATIENTS THAT ARE NOT OPIOIDS. AND SO PRACTITIONERS WHO REALLY HAVE CUT DOWN APPROPRIATELY IN MOST CASES ON THEIR OPIOID USE ARE LEFT WITH A PATIENT WHO IS IN PAIN. AND SO WHAT DOES ONE DO? THERE'S REALLY LIMITED DATA ON THE EFFECTIVENESS. THIS IS REALLY WORLD EFFECTIVENESS WE'RE TALKING ABOUT HERE, OF EXISTING THERAPIES, DRUGS, DEVICES, BEHAVIORAL INTERVENTIONS THAT HAVE ALREADY BEEN DEVELOPED FOR PREVENTING AND MANAGING PAIN WHILE REDUCING ADDICTION RISK. AND WE REALLY WANT THESE TO AFFECT THE GUIDELINES THAT CDC AND OTHERS HAVE PUT TOGETHER FOR BOTH PHARMACOLOGIC AND NON-PHARMACOLOGIC TREATMENTS, AND THIS IS REALLY BOTH FOR PATIENTS AND PRACTITIONERS. AND THESE TRIALS IMPORTANTLY ARE GOING TO BE CONDUCTED WITHIN THE CTSA PROGRAM NETWORK. THIS IS THE TRIAL INNOVATION NETWORK THAT I MENTIONED BEFORE. THE CTSA PROGRAM HAS WITHIN IT THESE CENTERS, HAVE TRULY MILLIONS, PROBABLY WE'RE STILL WORKING ON THE FINAL NUMBER, WELL OVER 100 MILLION PATIENTS THAT ARE TAKEN CARE OF AT THESE INSTITUTIONS, AND TYING ALL OF THOSE TOGETHER REALLY REPRESENTS AN ABSOLUTELY UNIQUE NATIONAL RESOURCE, BECAUSE THEY ARE CONNECTED, REMEMBER, WITH MANY OF THE BEST ACADEMIC MEDICAL CENTERS WHERE THE KOLs ARE, IT'S A DREAM TEAM IN ALL KINDS OF WAYS. TRIAL INNOVATION NETWORK PROVIDES DATA, CLINICAL BIOSTATISTICAL COORDINATION, RECRUITMENT, ET CETERA, AND PAIN EXPERTS ARE INVOLVED, WE HAVE TO HAVE PAIN EXPERTS INVOLVED AS WELL. AND LIKE EVERYTHING THAT I SHOWED YOU ON THE PRE-CLINICAL SIDE THESE ARE ALL DONE AT COLLABORATIONS WITH INVESTIGATORS OR OTHER INSTITUTES, CENTERS, OFFICES, AND INTERESTING TWEAK HERE IS THAT TWO OF THE OTHER INSTITUTES, THE NATIONAL INSTITUTES OF CHILD HEALTH AND HUMAN DEVELOPMENT, NICHD AND NCI ASKED IF THEY HAD INCORPORATE TWO NETWORKS INTO THAT AND WE'VE DONE THAT AS WELL. THESE ARE THE THINGS WHICH THE TIN DOES. THOSE OF YOU DO CLINICAL RESEARCH WILL RECOGNIZE THESE. THESE ARE ALL THINGS WHICH ARE REALLY GENERIC FOR EVERY TRIAL AND SO THEY SEND TO GET REBUILT OVER AND OVER, AND EXPERTISE DEVELOPED AND THEN DISBANDED FOR EVERY TRIAL, IN OUR VIEW TERRIBLY INEFFICIENT. AND REALLY DETRIMENTAL TO HEALTH OF PATIENTS AND ADVANCEMENTS OF SCIENCE AND MEDICAL CAREERS. THAT'S REALLY WHY -- ONE OF THE REASONS WE PUT THE TIN TOGETHER. ALL OF THESE THINGS ARE PROVIDED BY THE TIN, AND SO WHERE ARE WE NOW? RICK, YOU WEREN'T AT THIS MEETING, ACTUALLY, WERE YOU? YOU WERE ON THE PHONE? YEAH. SO RICK IS ON THE MULTI-DISCIPLINARY WORKING GROUP THAT HELPS TO GOVERN THE HEAL PROGRAM, AND WE HAD A VERY LONG AND EXHAUSTIVE AND EXHAUSTING MEETING BACK IN AUGUST ABOUT HOW TO DISBURSE THE FIRST YEAR'S MONEY AND WE ANTICIPATE THESE AWARDS BETTER COME OUT BY THE END OF SEPTEMBER BECAUSE THAT'S WHEN THE FISCAL YEAR ENDS. SO WE'RE -- IT'S A LITTLE BIT -- WE'RE BITING OUR FINGER NATURES -- FINGERNAILS, BUT THESE WILL COME OUT BY THE END OF THE YEAR. PLANS PHASE WILL BEGIN IMMEDIATELY AFTER THAT AND WE'LL HAVE THE KICKOFF MEETING IN NOVEMBER. I WANT TO STRESS THIS IS VERY UNUSUAL FOR AN NIH, THE WAY NIH NORMALLY DOES BUSINESS. NORMALLY WHAT ONE WOULD DO IS SAY, OKAY, I HAVE A PROBLEM, I'M GOING TO CREATE DE NOVO A NEW NETWORK. THAT'S HAPPENING ELSEWHERE IN THE HEAL PROGRAM. BUT THAT OBLIGATES YOU TO TWO YEARS, SOMETIMES EVEN LONGER, OF FINDING THE INVESTIGATORS, CREATING THE DATA COORDINATING CENTER, DOING ALL OF THE INFRASTRUCTURAL WORK THAT ONE HAS TO DO TO GET A TRIAL OFF THE GROUND. THIS IS ALREADY DONE HERE. SO WE CAN LAYER THE TRIALS ON TOP OF THIS ALREADY EXTANT INFRASTRUCTURE AND WE'RE OFF TO THE RACES, WHICH WE THINK IS OF COURSE A MUCH BETTER WAY TO DO BUSINESS FOR EVERYBODY INVOLVED, BUT PARTICULARLY FOR PUBLIC HEALTH CRISIS OF THIS SORT I THINK IS PARTICULARLY FITTING. LASTLY, AGAIN, APOLOGIES FOR THE FORMATTING HERE, DEVELOPING DRUGS AND TESTING PLATFORMS, THIS IS THE PRE-CLINICAL PART OF HEAL . YOU PROBABLY REMEMBER THERE'S SIX PIECES OF THIS, THE ONLY ONE I WANT TO ADDRESS JUST BRIEFLY HERE IS THE ONE ON DEVELOPMENT OF NEW CHEMICAL STRUCTURES TO MODULATE NOVEL TARGETS. THE IDEA IF WE'RE GOING TO GET INTO THE KINDS OF INTERVENTIONS, DRUGS FOR INSTANCE, WHICH WILL BE NON-ADDICTIVE PAIN MEDICINES OR ADDICTION MEDICINE, PROBABLY NOVEL MOLECULAR TARGETS, AND WE'RE PROBABLY GOING TO NEED NOVEL CHEMICAL MATTER TO ADDRESS THEM, HOW DO WE GET AT THAT NOVEL CHEMICAL MATTER NEW AND EFFICIENT WAYS, THIS IS WHAT ASPIRE IS ABOUT. ONE ASPECTS VIA A CHALLENGE, RELATIVELY NEW TO NCATS, YOU'RE FAMILIAR WITH HOW CHALLENGES WORK. BACKWARDS FROM HOW WE NORMALLY DO THINGS, NORMALLY WE PUT OUT AN APPLICATION, WHAT DO YOU WANT TO DO, AND THEN YOU WRITE SOMETHING WHICH HOPEFULLY CONVINCES THE PEER REVIEWERS AND US THAT YOU KNOW WHAT YOU'RE DOING AND WE GIVE YOU MONEY AND YOU EITHER DO OR DO NOT SUCCEED IN THE GOALS THAT YOU SAID YOU WERE GOING TO ACHIEVE. IN THIS CASE, IT'S COD. CASH ON DELIVERY. YOU HAVE TO COME UP WITH THE SOLUTION AND IF YOU DO, YOU GET THE MONEY. AND SO IT'S A VERY DIFFERENT WAY TO DO BUSINESS. LOTS OF COMPANIES DO THIS, LOTS OF ORGANIZATIONS. WE'VE DONE IT OURSELVES. NOT FOR MONEY IN THE PAST BUT THIS IS FOR A MONETARY PRIZE. PHASE IS WAS FEASIBILITY IN THE LAST YEAR, THOSE WINNERS HAVE BEEN SELECTED AND WE'RE GOING TO ANNOUNCE THOSE AT THE END OF NEXT MONTH AT A MEETING, AND FEASIBILITY TO PRACTICE WILL ROLL OUT EARLY PART OF FISCAL YEAR PROBABLY NEXT MONTH FOR EACH, CHEMISTRY DATABASE, PORTAL, ALGORITHMS FOR DEVELOPING NOVEL STRUCTURES, ASSAYS AND INTEGRATED SOLUTION. THAT WAS A WHIRLWIND TOUR THROUGH A VERY SELECTED GROUP OF THINGS THAT HAVE GONE ON HERE SINCE THE LAST MEETING BUT I HOPE IT GIVES YOU A SENSE OF WHAT IT'S LIKE TO WORK AT NCATS. I LIKE WORKING IN A WIND TUNNEL BECAUSE THERE'S AN AMAZING AMOUNT OF EXCITING STUFF GOING ON. AND I WANTED TO GIVE YOU A SENSE OF THOSE. I I'M NOT SURE WHAT TIME WE HAVE FOR DISCUSSION BUT WE WOULD BE INTERESTED IN REFLECTING ON THIS. WHAT I JUST TOLD YOU, WITH THE CAVEAT THEE ARE SELECTIONS. ARE THERE THINGS WHICH ARE KIND OF COOL BUT MAYBE NOT, YOU KNOW, NOT FIRST PRIORITY, THAT WE OUGHT TO STOP DOING? ARE THERE THINGS THAT YOU THINK ARE RIGHT ON THE MONEY THAT WE OUGHT TO JUST PUT ALL OUR CHIPS ON, ET CETERA? THAT'S THE KIND OF DISCUSSION WE'RE INTERESTED IN HAVING. SO HOW MUCH TIME DO WE HAVE? >> (INAUDIBLE). >> YEAH, BECAUSE WHEN DID WE START? >> (INAUDIBLE). >> OKAY. SO MAYBE JUST A FEW QUESTIONS OR COMMENTS IF THERE ARE SOME AT THIS POINT. BRAD? >> CAN I ASK, SO IN BUSINESS WHEN YOU -- IF YOU'RE STARTING DOWN THE THERAPEUTIC PATH AND IDENTIFY A TARGET, I MEAN, THAT EARLY BEFORE YOU EVEN ARE STARTING ON ANY SCREENING ASSAY DEVELOPMENT, YOU USUALLY DISCUSS LIKE THE PATH FORWARD, SO WHEN YOU GET TO DEVELOP A PATH, IS IT REALISTIC FOR YOUR COMPANY TO DO THAT OR WILL YOU BE PARTNERING, ALL THE WAIT TO WHEN YOU GET TO THE MARKET, WHAT'S THE TARGET PROFILE, IS THERE REIMBURSEMENT AVAILABLE, ALL THOSE KINDS OF THINGS. IF YOU TAKE THE PRE-CLINICAL 3D TISSUE THING YOU TALKED ABOUT, NOT THE TISSUE CHIP BUT THE EARLIER ONE, AS YOU EMBARK ON THIS AND STARTED SEEING 3D MIGHT BE MORE PREDICTIVE, IF IT WORKS, IS THIS GOING TO BE PROVIDED TO CROs? WILL IT BE PROPRIETARY? HOW IS INDUSTRY OR ECONOMICS GOING TO USE IT, IF IT WORKS? ING >> YEAH. >> THE SAME THING WITH THE ADDRESSING THE OPIOID CRISIS, YOU KNOW, HAS SOMEONE BESIDES SAID LET'S LOOK FOR AGENTS THAT ADDRESS ADDICTION BETTER OR ADDRESS PAIN WITHOUT CAUSING ADDICTION, IF YOU GOT -- ESPECIALLY ADDICTION ONES, IF YOU ACTUALLY GOT ONE REMARKABLE IN ANIMALS, PUT IN TRIALS, AND ASSUMING YOU FUNDED IT FOR THE TRIALS AND LEAD INVESTORS, EVEN THEN WHEN YOU GET TO MARKET WILL THERE BE COMPLIANCE, REIMBURSEMENT, SUCH THAT INDUSTRY HAD WITH ADDICTION DRUGS, RIGHT? MY QUESTION IS ACTUALLY AT NCATS WHEN YOU'RE IN THE VERY BEGINNING INNINGS DOES SOMEONE DO MODEL OUT WHAT WOULD THE PATH BE LIKE ALL THE WAY AS WE'RE FORCED TO DO IN INDUSTRY? >> YEAH, YEAH, IT'S A GREAT QUESTION. I WOULD SIGH COMPARED TO MY TIME IN INDUSTRY WHERE WE ABSOLUTELY DID THAT FROM THE VERY BEGINNING, THOUGH WE THINK ABOUT IT, IN THE EARLIEST ONES WE ACTUALLY DON'T DO THAT ON PURPOSE, ACTUALLY. SOMETIMES FOR QUITE DIFFERENT REASONS SOMETIMES. IN THE ITCH EXAMPLE, THAT ONE CAME TO US AS A REALLY CHANCEY THING. AND COULD WE DEVELOP A TECHNOLOGY THAT WOULD ALLOW US TO VALIDATE OR QUALIFY THIS TARGET FOR FURTHER DEVELOPMENT OR NOT? AND SO, THE ENDPOINT WAS A TOOL TO VALIDATE THE THERAPEUTIC HYPOTHESIS AND THE IDEA IS SORT OF TRADITIONAL IN THAT WAY, THAT WE'LL DEVELOP THESE THINGS, PUBLISH THE DATA, AND HOPEFULLY PEOPLE ARE INTERESTED IN ITCHING WILL SAY, OH, HERE'S A NOVEL TARGET AND THEY CAN PICK IT UP AND RUN WITH IT. CERTAINLY IF THE COLLABORATORS WANT TO APPLY TO ANOTHER PROGRAM AT NIH OR COULDN'T APPLY TO TREND BECAUSE ITCH IS NOT A RARE DISEASE, WE WOULDN'T WORK ON IT IN THE PRE-CLINICAL PART BUT THE IDEA BEING THAT WE WANT TO BE ABLE TO TAKE A LOT OF RISK WITHOUT ANY COMMERCIAL CONCEPT FROM THE BEGINNING. AND WHEN WE'RE TALKING ABOUT THE TREND PROJECTS, IT'S VERY MUCH A CONSIDERATION BECAUSE OUR FEELING THERE IS THE RESULT IS NOT SO MUCH A SCIENTIFIC ADVANCE AS IT IS IN THE ITCH EXAMPLE OR TOOL TO DO THERAPEUTIC -- TESTING OF THERAPEUTIC HYPOTHESIS. IT IS A DRUG DEVELOPMENT PROGRAM, THE INTENT OF WHICH IS TO GET ON THE MARKET. ON THE OTHER HAND, NCATS IS NOT A DRUG DEVELOPMENT ORGANIZATION AND SO WE THINK ABOUT THIS MUCH LIKE AN INVESTOR WOULD, AND YOU DO IN YOUR ORGANIZATION, WHAT CAN WE DO TO MAKE THIS AS SAID SO ATTRACTIVE THAT OTHER PEOPLE ARE GOING TO WANT TO INVEST IN IT? AND SO WHAT ARE ALL THE PROBLEMS THAT A PRIVATE SECTOR INVESTOR MOST OFTEN WOULD WANT TO KNOW TO DE-RISK THIS ENOUGH SO THAT EVEN IF IT'S A MARGINAL APPROACH WITH RELATIVELY GENERIC DRUG, THAT THEY WOULD BE WILLING TO TAKE THE PLUNGE ON IT. SO WE DO THINK ABOUT IT. BUT WE TRY NOT TO HAVE THE KINDS OF NPV REQUIREMENTS THAT COMPANY WOULD HAVE, IT'S ONE OF THE ADVANTAGES WE HAVE HERE. I THINK ON THE 3D TISSUES, WE'RE REALLY I'D SAY WHERE WE WERE WITH TISSUE CHIP IN 2014, THAT IT LOOKS PRETTY PROMISING, BUT IS JUST VERY EARLY DAYS, AND SO WHAT WE WERE FOCUSING ON IS HOW DO WE DEVELOP A PLATFORM WHICH AS POTENTIALLY USEFUL TO AS MANY PEOPLE AS POSSIBLE, DEMONSTRATE ENOUGH OF THAT POTENTIAL THAT OTHER PEOPLE WOULD BE INTERESTED, AND THEN PROMULGATE AS MANY OF THE DATA AS WE CAN. AND JUST MAKE ALL THE DATA PUBLIC, TO ENABLE OTHER PEOPLE TO DO THIS. AND SO THAT'S REALLY THE APPROACH. I MUST SAY WHAT IS STARTING TO HAPPEN AND WE CERTAINLY EXPLICITLY ARE TRYING TO DO IN HEAL AND OTHER PROGRAM ALSO NOW IS COMBINE THESE PROGRAMS WITHIN NCATS, TO ACTUALLY TEST WHETHER THE 3D TISSUES ARE BETTER THAN 2D, OR NOT. OR DO TISSUE CHIPS -- ANTON AND HIS GROUP ARE WORKING WITH TISSUE CHIP PLATFORMS, ARE THEY ACTUALLY BETTER OR NOT AT BEYOND THE CANONICAL COMPOUNDS AND RETROSPECTIVE ANALYSES, DO THEY ACTUALLY WORK? AND THAT'S QUITE EARLY CASE, BUT THAT'S VERY MUCH THE INTENTION. GREAT QUESTION THOUGH. >> YOU ASKED A BROAD QUESTION AS TO THE FEEDBACK, HOW IS NCATS DOING AND HOW DOES IT ALIGN, MAYBE I'LL GIVE A LITTLE BIT OF PERSPECTIVE FROM THE FOOD AND DRUG ADMINISTRATION. >> YEAH. >> I THINK THE COLLABORATION UNDER HHS BETWEEN THE TWO AGENCIES IS REALLY CRITICAL TO INFLUENCE HEALTH CARE OR WELLNESS ECOSYSTEM THAT OCCUPIES OR HAS A FOOTPRINT OF MORE THAN 20% OF OUR GDP. >> YEAH >> AND HOW ARE WE DOING? AND HOW DO YOU MEASURE IT? I THINK LIFE EXPECTANCY IS DECLINING CURRENTLY AND WE NEED TO DO SOMETHING ABOUT IT, GREAT OPPORTUNITIES TO ALIGN NOT JUST RESOURCES BUT ALSO BE SYNERGISTIC, THAT'S WHAT NCATS IS TARGETING AND I WOULD ENHANCE AND COMMEND YOU, ALSO TRYING TO REACH OUT AND PROVIDING PLATFORMS THAT ARE BROADER THAN GOVERNMENT, THEY HAVE GREAT OPPORTUNITY TO LEVER YANG KNOWLEDGE AND -- LEVERAGE KNOWLEDGE, YOUR PROGRAMS ARE INCLUSIVE OF THAT BECAUSE IF WE WANT TO PUT OUR, LET'S SAY, BUSINESS MODEL OF HEALTH CARE OR SICK CARE FROM ITS DOWN SIDE, LIKE UP ON ITS FEET, WE NEED TO BE PREVENTIVE AND PREDICT AND PROJECT AND LEVERAGE WHAT WE'VE GENERATED AND MAKE IT ACCESSIBLE. THE PRINCIPLES HAVE BEEN TALKED ABOUT SO LEVERAGING TOWARDS PREDICTION AND PROJECTION TO MAKE HEALTH CARE PREVENTIVE AND CHANGING THE BUSINESS MODEL IS CRITICAL. THAT'S A MAJOR PUSH WE HAVE TO DO UNDER HHS BECAUSE OTHERWISE WE CANNOT PAY. >> IT'S A GOOD POINT. IT'S A POINT THAT ACTUALLY BRAD MADE IN A DIFFERENT SETTING, WHICH WAS NCATS DOES QUITE PROUDLY TAKE A DIFFERENT APPROACH FROM THE REST OF NIH. FOR VERY GOOD REASONS. MOST OF THE NIH STARTS WITH THE THESIS THAT UNFETTERED CURIOSITY-DRIVEN RESEARCH AS IT'S CALLED IS THE BEST ROUTE TO ADVANCING SCIENCE AND HUMAN HEALTH. THE BASIC WORLD, MY OWN OPINION IS THAT THE BEST WAY. BUT IN THE TRANSLATIONAL WORLD, WE REALLY HAVE TO BEGIN WITH THE END IN MIND. WE HAVE TO THINK WHERE WE'RE TRYING TO GO AND WORK BACKWARDS. WHICH IS MORE THAN ENGINEERING APPROACH, IT'S THE WAY ENGINEERS THINK, NOT NECESSARILY BIOLOGISTS THINK. AND YOU DISCOVER A LOT OF GREAT SCIENCE IN THAT SPACE BUT IT'S JUST A DIFFERENT WAY OF THINKING. SO THAT'S WHY WHEN DAN STARTED THE TISSUE CHIP PROGRAM, HE REACHED OUT TO FDA FROM THE VERY BEGINNING, AND WHEN WE TRY TO TREND THE FIRST PERSON I CALLED WAS JANET WOODCOCK. IF WE DO ALL THIS WONDERFUL WORK AND IT DOESN'T GO ANYWHERE, THEN WHY HAVE WE BOTHERED? THAT'S AN ATTITUDE THAT PERVADES ALL OF OUR PROGRAMS. AND I HOPE YOU WILL CONTINUE TO CATCH US ON THIS, IN ORDER TO SAY, YOU KNOW, I DON'T SEE THE CONNECTION HERE, MUCH LIKE WHAT BRAD JUST ASKED. I HOPE YOU'LL CONTINUE TO DO THAT. OR SAY, GOSH, YOU OUGHT TO BE WORKING WITH SO-AND-SO, ONE OF THE THINGS THAT'S GREAT ABOUT THE CURES ACCELERATION NETWORK BOARD IS WE HAVE PEOPLE ON THE BOARD NEVER ASSOCIATED WITH NCATS, SORRY, WITH NIH COUNCILS FOR THE MOST PART. WE HAVE REPRESENTATIVES FROM FDA, FROM V.A., FROM THE NSF, PARTS OF THE RESEARCH ECOSYSTEM THAT ARE CRITICAL IN WHAT WE DO AND YET NORMALLY WE DON'T WORK WITH THEM. WE HAVE BY STATUTE -- THEY HAVE TO BE HERE. SO WHOEVER MADE THE CAN LEGISLATION KNEW WHAT THEY WERE DOING, AND IT REALLY MAKES US EASY -- MAKE IT EASY FOR US TO DO WHAT YOU'RE DESCRIBING, WHICH WE COMPLETELY AGREE IS THE WAY TO WORK. >> IF I COULD ADD TO THAT, CHRIS, THAT THE "CAN" REVIEW BOARD ALSO HAS ADDITIONAL AUTHORITIES BEYOND THOSE OF NCATS OR OTHER I.C.s TO INCLUDE EXTRA NIH ENTITIES IN THAT KIND OF COLLABORATIVE EFFORT. >> YES >> THESE ARE AUTHORITIES WE'LL BE TALKING ABOUT LATER TODAY. >> RIGHT. >> THAT WE REALLY NEED TO EXPAND UPON. >> OKAY. GOOD. >> ALL RIGHT, FOLKS. THANK YOU, CHRIS. WE ARE GOING TO HAVE A SHORT BREAK. LET'S BE BACK AT 11:35 AND WE'LL HAVE THE CAN REVIEW BOARD PRESENTATION. >> WELCOME BACK, EVERYBODY. WE'RE NOW GOING TO THE CAN REVIEW BOARD PORTION OF OUR PROGRAM. HERE WE ARE. SO LYNN MARKS IS GOING TO DO THE -- WHO IS THE CHAIRPERSON OF THE CAN REVIEW BOARD, IS GOING TO DO THIS UPDATE. AND THEN THERE'S GOING TO BE A NUMBER OF PEOPLE, RON, BOBBY AND P.J. BROOKS WILL HAVE THINGS TO SAY. LYNN OR RON? HOW SHOULD WE -- >> THANKS, CHRIS. YES, ANN RATHER THAN P.J. WILL HELP US WITH THE GENE THERAPY PIECE OF IT. SO, WELCOME, EVERYBODY, TO THE CAN REVIEW BOARD UPDATE. WE'RE GOING TO DO A BIT OF TAG TEAM AS CHRIS TALKED ABOUT, THE TOPICS WE WANT TO COVER. WE WANT TO FOCUS ON THE TWO PROJECT PROPOSALS WE'RE WORKING ON WITH GENE THERAPY. AS WELL AS A NEWER INITIATIVE, SLIGHTLY BEHIND THE GENE THERAPY ONE, THE DRUG REPURPOSING EFFORT. AND THEN I'D LIKE TO HAVE A CONVERSATION WITH YOU ABOUT THE CONVERSATION RON AND I HAD WITH JODY AND CHRIS AND ANNA ABOUT HOW THE CAN REVIEW BOARD IS BE MORE EFFECTIVE AND HELPFUL IN OPTIMIZING OUR IMPACT ON NCATS AND THERE BY THE COMMUNITY AT LARGE. JUST A QUICK REMINDER OF THE PROCESS WHEN WE COME THROUGH THESE PROJECTS BECAUSE PEOPLE ARE ANXIOUS TO PUT OUT SOLICITATIONS AND MAKE AWARDS, BUT WE'RE ON THAT JOURNEY. I WOULD ARGUE WITH ANNA AGREEING WE'RE IN THE FOCUS AREA SPACE, WE'LL MOVE ONES WE'VE GOTTEN A LOT OF INPUT FROM THE MEETINGS AND CONFERENCES THAT WE'RE HAVING, WE'LL MOVE MORE TO THE CONCEPT PHASE, AND THEN PUT OUT SOLICITATIONS AND MAKE AWARDS, ET CETERA. SO WE'RE ON THAT JOURNEY, TAKES A BIT OF TIME BUT I THINK THE EFFORT THAT WE'RE PUTTING INTO UNDERSTANDING THE ISSUES, LISTENING TO STAKEHOLDERS, AND THEN MAPPING OUT OUR APPROACH WILL SERVE US WELL AS WE GO DOWNSTREAM ON THIS OVERALL PROJECT. AND JUST TO FORESHADOW THE DISCUSSION AT THE END IT WOULD BE LOOKING BACK ON THIS AS AN OVERALL APPROACH, HOW ARE WE LEVERAGING OUR AUTHORITIES, HOW ARE STAKEHOLDERS, HOW ARE WE ONBOARDING AND OFFBOARDING PROJECTS OVERALL IN THE PROCESS AND ARE WE OPTIMALLY DOING THAT AS OUR ROLE IN PART OF THE NCATS FAMILY. SO WITH THAT AS AN INTRODUCTION, WE'RE GOING TO BOUNCE OVER TO RON AND ANN. >> THANK YOU, LYNN. I'D SAY THAT MOST OF THE PEOPLE HERE IN THE ROOM HAVE HEARD US TALK ABOUT OUR GENE THERAPY PROGRAM, A GOOD NUMBER OF TIMES. SO I'LL TRY TO BE BRIEF AND REFER TO THE FACT THAT AS MOST OF YOU MIGHT RECALL, OUR CONCENTRATION ON GENE THERAPIES SPRANG FROM TWO-DAY CONFERENCE HERE AT THE NIH CO-HOSTED BY CHRIS AND WILSON BRIAN OF CBER, IN AUGUST, IT WAS CLEAR THERE WERE ONLY ABOUT FIVE OR SIX DIFFERENT ISSUES THAT WERE CONFOUNDING ALL THE GENE THERAPY PROGRAMS WE HEARD ABOUT. THEY WERE HAVING VARIOUS LEVELS OF SUCCESS IN THOSE GENE THERAPY PROGRAMS BUT ALL THE CONFOUNDERS WERE THE SAME. SO, THE CAN REVIEW BOARD WAS ABLE TO IDENTIFY THE SIX ISSUES WE THOUGHT WERE MOST COMMONLY THE CON FOUNDERS OF ALL THAT CLINICAL RESEARCH IN GENE THERAPY, AND I WON'T BELABOR EACH BUT YOU CAN SEE THERE'S A LOT ABOUT STANDARDIZATION. IN BOTH PREDICTIVE MEASURES AND ASSAYS. A LOT REVOLVING AROUND IMMUNE RESPONSE, IMMUNOGENICITY IS A KEY FACTOR IN ALL THE CLINICAL TRIALS. GOOD DEAL OF EFFORT TO STANDARDIZE ASSAYS FOR POTENCY AND BIODISTRIBUTION, FOR EXAMPLE. MANUFACTURING LOOMED THE LARGEST OF THE CONFOUNDERS, WE'LL TALK A LITTLE BIT ABOUT THAT MORE LATER. BUT IT'S CLEAR THAT MANUFACTURING WAS THE LONGEST POLE IN THE TENT IN TERMS OF IT'S TAKING WAY TOO LONG TO MANUFACTURE ENOUGH VECTOR TO DO EVEN SMALL CLINICAL TRIALS. AND IT'S WAY TOO EXPENSIVE AND REALLY THE LARGE COMPANIES ARE DOING IT ON THEIR OWN. AND THEY ARE PUTTING A COUPLE HUNDRED MILLION DOLLARS INTO MANUFACTURING FACILITIES, THE SMALL INVESTIGATORS CAN'T DO THAT, AND WE HAVE TO EMPOWER ALL OF THOSE TO GET FURTHER ALONG WITH OUR 7,000 RARE DISEASES, FOR EXAMPLE. WE LOOKED AT THE NEED FOR SCIENTIFIC TOOLS TO INFORM CLINICAL TRIAL DESIGN AND THEN THERE WAS A SUBSET OF OUR CONSIDERATION OF POSSIBILITY OF NON-VIABLE VECTORS IN GENE THERAPY. SO SEEING THAT ALL THOSE WERE THE CONFOUNDERS, WE LOOKED AT THE POSSIBILITY OF ADVANCING TRANSLATIONAL SCIENCES THAT COULD PROVIDE PLATFORMS THAT WOULD BE BROADLY APPLICABLE AND AVAILABLE. BUT NCATS? SOUNDS LIKE A VERY NCATS-IAN THING TO DO TO COME UP WITH PROJECTS THAT CAN EMPOWER AND THE SMALL INVESTIGATOR EMPOWER THAT EARLY STAGE CLINICAL TRIAL, AND BY PROVIDING TRANSLATIONAL ADVANCED TECHNOLOGY PLATFORMS WE CAN SOLVE ISSUES FOR EVERYBODY. AND HAVING NCATS INVOLVED MAKES CERTAIN IT WILL BE AVAILABLE TO ALL. NONE OF THESE COMPANIES WITH PUT I.P. IN THEIR HIP POCKETS AND SAY THIS IS MINE. SO IT'S BROADLY AVAILABLE TO EVERYBODY. WE DECIDED TO DO, WITH YOUR APPROVAL, THIS PAST JANUARY WAS DEVELOP A SERIES OF WORKSHOPS AND CONFERENCES TO EXPLORE SOLUTIONS WE COULD TRANSLATE INTO GRANTS LATER THAT FOR PROJECTS THAT WOULD DEVELOP THE SOLUTIONS. AND THE FIRST ONE THAT WE CONDUCTED OURSELVES WAS OF A FANTASTIC WORKSHOP ON JUNE 11 RIGHT HERE AT THE NIH. IT WAS ON THE USE OF AAD, IN GENE THERAPY FOR CNS. AND IT SOLD OUT IN A HEARTBEAT. WE DIDN'T KNOW HOW THOROUGHLY ENGAGED PEOPLE WOULD WANT TO BE, AND SO WE SCHEDULED A BALCONY AT NATCHER AND WITH 100-PERSON CAPACITY, SOLD OUT IN THE FIRST FEW DAYS. THERE'S A LONG WAITING LIST. YOU CAN SEE HERE 100 PEOPLE IN THE ROOM AND 800 PEOPLE LIVE ON THE WEB STREAM, 400 HAVE VIEWED THE ARCHIVE, SO TOTAL OF 1200 VIEWS ONLINE. AND OVER 30 COUNTRIES. SO YOU CAN SEE THE INTENSITY OF INTEREST IN THIS VERY CRITICAL ELEMENT OF GENE THERAPY. THE GOALS THAT WE ASSESSED WERE PRETTY CLEAR. WE WANTED TO REVIEW ALL THE CLINICAL DATA TO DATE, WHICH WAS STARTED IN THAT CONFERENCE LAST AUGUST. WE WANT TO DISCUSS ANIMAL MODELS AND ASSAYS, AND WE COMMITTED RIGHT AWAY TO A PUBLICATION OF THE PROCEEDINGS BECAUSE WE SAW THE INTEREST. WE SAW THE ENGAGEMENT. AND SO THAT IS IN PROCESS. WE ARE IN THE PROCESS OF DEVELOPING PROCEEDINGS PUBLICATION. IN THE MEANTIME, WE ALSO BEGAN TO PARTICIPATE AND HELP PLAN, PRESENT AT OTHER CONFERENCES THAT WERE ALREADY BEING SCHEDULED BY OTHER ORGANIZATIONS, THE FIRST ONE WAS BY U.S. PHARMACOPEIA, ALL ABOUT STANDARDIZATION, WE GOT THEIR COMMITMENT ON STANDARDIZING ASSAYS AND MEASURES. WE SPOKE AT -- AND PARTICIATED IN THE ANNUAL MEETING OF NIMBLE, NATIONAL INSTITUTE FOR MANUFACTURING BIOLOGICS AND GOT THEIR COMMITMENT TO HELPING US ON THE MANUFACTURING PIECE. SO, BACK TO THIS CNS AAV MEETING WE HAD ON JUNE 11, IT WAS JUST FANTASTIC. I'D LIKE TO EMPHASIZE THE KEY POINTS HERE THAT IT WAS OBVIOUS TO EVERYONE WE NEED TO BE BETTER AND BETTER AT SHARING NOT ONLY CLINICAL DATA BUT PRE-CLINICAL DATA TO ADVANCE EVERYBODY IN THIS FIELD. WE NEED BETTER STANDARDIZATION OF IMMUNOGENICITY MEASUREMENTS AND ASSAYS. AND MORE CONSISTENT PRACTICES AND IMMUNE TOLERANCE STRATEGIES. THE FEEDBACK IS FANTASTIC. TWO DAYS AGO AT A CONFERENCE I WAS APPROACHED BY TWO OR THREE, WHERE IS THE NEXT WORKSHOP ON YOUR GENE THERAPY PROGRAM AND CAN YOU PLEASE INCLUDE ME? SO THAT'S HAPPENING TO ALL OF US. ANN AND I AGREE BY THE WAY WE LEASHED -- LEARNED A LOT OF LESSONS, WE NEED A BIGGER VENUE FOR THE WORKSHOPS. WE'VE GOT ONE MORE WORKSHOP COMING UP THIS NOVEMBER BY THE SAME INSTITUTION THAT CHRIS SPOKE CONSIDERABLY ABOUT ALREADY TODAY. THE NATIONAL -- USED TO BE CALLED NATIONAL ACADEMY OF SCIENCES, NOW NATIONAL ACADEMY OF SCIENCE, ENGINEERING AND MEDICINE. THEY ARE GOING TO BE DOING A WORKSHOP IN NOVEMBER ON EXPLORING NOVEL CLINICAL TRIAL DESIGNS FOR GENE THERAPY. WE'VE BEEN INVITED TO -- WE SPOKE AT THEIR PLANNING COMMITTEE MEETING AND ARE BEING INVITED TO PRESENT AT THAT ONE. I'LL TURN TO ANNE PARISER TO TELL YOU ABOUT THE ONES COMING UP NEXT YEAR >> THANKS. I DON'T HAVE A LOT TO ADD TO WHAT RON SAID BUT WE'RE CONTINUING ON WITH SOME OF THE REALLY HIGH INTEREST AREAS THAT WE'D LIKE TO CONVENE. SO IN ADDITION TO THE MEETING IN NOVEMBER, NCATS IS CO-SPONSORING WITH FDA CBER, EXPECTED TO CO-SPONSOR THE JANUARY MEETING ON MANUFACTURING, FDA TAKING PART IN PLANNING COMMITTEE, HAVING SPEAKERS. AND THAT'S REALLY TRYING TO ADDRESS AT THE MANUFACTURING CAPACITY IN PARTICULAR ISSUES WHICH IS A CRITICAL ISSUE AT THE MOMENT. AND IN JULY, WE RECENTLY FOUND A DATE FOR THE SYSTEMIC IMMUNOGENICITY CONCERNS, AND AGAIN FDA IS A SO CO-SPONSOR, WE'VE IDENTIFIED CO-CHAIRS RIGHT THERE. BOTH MEETINGS WILL BE HELD AT THE NATCHER AUDITORIUM, AS RON SAID ONE THING WE'VE CLEARLY LEARNED IS THERE'S TREMENDOUS INTEREST IN THIS FROM EVERYWHERE, INCLUDING PATIENT COMMUNITIES AND WE WANTED TO MAKE SURE ANYBODY WHO WANTED TO TODAY CAN ATTEND. ALL THESE MEETINGS ARE WEBCAST, WILL CONTINUE TO BE WEBCAST AS WELL. I ALSO WANTED TO MENTIO WE'RE NOT THE ONLY ONES HOLDING THEIR MEETINGS. NINDS IS HOLDING A GENE THERAPY MEETING, TWO-DAY MEETING NEXT WEEK FOR NEURODEVELOPMENTAL DISORDERS. ARE THERE QUESTIONS ON THAT? >> SO, NOW I'D LIKE TO INTRODUCE BOBBY ANN MOUNT, WHO WILL GIVE YOU A PRESENTATION ON DRUG REPURPOSING FOR CAN REVIEW BOARD. >> YOU SAW CHRISTINE GIVE THE PRIOR PRESENTATION, PRESENTED TO CAN REVIEW BOARD, I WORK FOR CHRISTINE, MANAGING INITIATIVES ON THERAPEUTIC USES, SHE COULDN'T BE HERE TODAY SO I'M GOING TO GIVE THE PRESENTATION. SO THERE ARE TWO SLIDES THAT GIVE SOME HISTORICAL PERSPECTIVE, WHAT WE'VE ALREADY PRESENTED TO YOU AT CAN REVIEW BOARD. THIS FIRST SLIDE WAS PRESENTED BY CHRISTINE IN JANUARY, A LIST OF CHALLENGES FROM PRIOR CONFERENCES CAN FDA, CMS AND OTHERS, TO MAKE THIS A REALITY. THIS IS AN AREA THAT HAS A LOT OF CHALLENGES THAT NOW SINGLE ENTITY OWNS, SO THAT MAKES THEM CHALLENGING TO SOLVE. SO BECAUSE CAN REVIEW BOARD WAS ENTHUSIASTIC ABOUT THIS TOPIC THEY IN THE SUBSEQUENT MEETING IN MAY RECOMMENDED WE WOULD HOST A WORKSHOP TO DISCUSS THE CHALLENGING ISSUES. WHILE THE FIRST SLIDE SHOWS WHAT WE PRESENTED, SOME OF THE GENERAL TOPICS REMAIN THE SAME BUT WHAT WE'RE DOING AT THE WORKSHOP HAS MORPHED A LITTLE BIT, I'LL GIVE THE OVERALL AGENDA AT THE END OF THE SLIDE PRESENTATION. BUT SAVE THE DATE IS ON THIS SLIDE. THE VENUE, WE RECEIVED A LOT OF HELP FROM OFFICE OF SCIENTIFIC REVIEW, PARTICULARLY GETTING THE VENUE, HEALTH AT HILTON ROCKVILLE, NEAR A METRO STOP ON THE RED LINE. HELD ON DECEMBER 5 AND 6, THE TITLE REPURPOSING GENERIC DRUGS, RESEARCH AND REGULATORY CHALLENGES, AND THE TOPIC IS ACTUALLY BROADER THAN GENERIC. IT'S REALLY FROM A REGULATORY PERSPECTIVE TO BE MORE ACCURATE, OFFPATENT DRUGS, NOT SURE HOW MANY PATIENTS GO TO THE PHARMACY AND ASK, SO FOR THE PUBLIC PRESENTATION WE'RE I THINK GENERIC IS MAYBE MORE RELATABLE. SO THE SCOPE OF THE MEETING WILL BE FOCUSING ON THE ROAD BLOCKS FOR WHY THERE ISN'T MORE DRUG DEVELOPMENT FOR DRUGS THAT HAVE LIMITED PATENT LIFE, LIMITED REGULATORY EXCLUSIVITY. WE'RE NOT FOCUSING ON PATENT LIFE, HOWEVER, BECAUSE NEXT MONDAY AND TUESDAY THERE'S A MEETING JUST ON THIS TOPIC IN THE D.C. METRO SO WE DIDN'T WANT TO DUPLICATE EFFORTS. THIS IS SOMETHING WE CAN'T DO BY OURSELVES SO WE HAD BEEN HAVING CONVERSATIONS FOR A LONG PERIOD OF TIME WITH OTHER GOVERNMENT AGENCIES AND IN PARTICULAR HEATHER STONE HAS BEEN OUR LIAISON TO FDA. SHE WORKS IN THE OFFICE OF MEDICAL POLICY. WE'RE ALSO GETTING HELP FROM REAGAN UDALL FOUNDATION, THEY HAVE EXPERTISE FROM A REGULATORY PERSPECTIVE IN DRUG DEVELOPMENT. THE LAST TWO SLIDES ARE JUST HIGH LEVEL OUTLINE OF THE AGENDA THAT WE COVERED AT THIS WORKSHOP. SO WITH INPUT FROM DR. AUSTIN, WE'RE TRYING TO FRAME THE WORKSHOP AS A SERIES OF ROAD BLOCKS, SOMEBODY WOULD ENCOUNTER IF THEY INTENDD TO REPURPOSE AND OFF-PATENT DRUG. WE'RE CALL IT ROAD BLOCKS IT'S MORE LIKE ICEBERG AND PEOPLE CAN SEE THE SURFACE WHAT THE ISSUES ARE BUT THEY ARE MORE COMPLICATED THAN THAT. WE WANT TO GET EVERYONE IN THE SAME PAGE AT THIS FIRST WORKSHOP, WHAT THE ISSUES ARE, AND THAT WORKSHOP FROM DAY ONE WILL BECOME AN EDUCATIONAL RESOURCE PUBLICLY AVAILABLE SO WE CAN BRING PEOPLE TO WHAT THE ISSUES ARE. WE WANT PEOPLE TO ATTEND IN PERSON. AFTER WE PRESENT THE ISSUES ON DAY 1, THERE'S GOING TO BE BREAKOUT GROUPS ON DAY 2 WHERE WE BRAINSTORM WITH A LOT OF DIFFERENT SECTORS, PEOPLE WITH DIFFERENT EXPERTISE, A LOT OF SMART PEOPLE IN THE ROOM AND FIGURE OUT WHAT IT IS WE CAN DO. SO DAY 1, WE'LL INTRODUCE THE WORKSHOP WITH THE PATIENT PERSPECTIVE. WE HAVE A PATIENT ADVOCATE WHO IS GOING TO TALK ABOUT HER EXPERIENCE BOTH POSITIVE AND NEGATIVE WITH REPURPOSED GENERIC DRUG AND GIVE OVERALL WHAT'S THE PROBLEMS. A LOT OF TIMES IN THE POPULAR PRESS PEOPLE PRESENT THIS AS SIMPLE, AND IT REALLY IS, BUT IT'S NOT AS EASY TO TACKLE AS IT SEEMS AT FIRST. SO TECHICALLY A PERSON COULD GET A NEW-USE PATENT FOR A DRUG, IT'S NOT THAT EASY TO ENFORCE THAT ACTUALLY THAT INVESTMENT GETS ANYTHING FOR WHOEVER INVESTED IN RESEARCH AND DEVELOPMENT FOR PATENT AND REGULATORY EXCLUSIVITY, THERE'S OTHER GENERIC COMPANIES, NO WAY TO TRACK, MAYBE IT COULD HAPPEN WITH USE OF ELECTRONIC HEALTH RECORDS IN THE FUTURE BUT RIGHT NOW THERE'S NO WAY TO ENFORCE. HOWEVER INVESTED THAT CAN RECOUP, SO THAT'S ONE BARRIER. WE'RE GOING TO GO THROUGH A DRUG DEVELOPMENT PIPELINE, STARTING AT PRE-CLINICAL AND GOING THROUGH CLINICAL DEVELOPMENT, WHAT ARE THE REALLY HIGH LEVEL ISSUES. SO WE'RE STARTING OFF WITH A SCENARIO WHERE A DRUG IS NOT YET USED OFF LABEL, SO NCATS HAS AN INTEREST IN SITUATIONS WHERE THERE'S NOT ENOUGH DATA YET FOR A GENERIC DRUG TO BE USED OFF LABEL. WHAT WE NEED TO DO TO PROVIDE ENOUGH DATA FOR THAT TO HAPPEN, AND THEN ON THE OTHER SIDE OF THE COIN FDA IS INTERESTED IN -- THERE ARE DRUGS ALREADY THAT PHYSICIANS ARE PRESCRIBED OFF LABEL BUT IT'S NOT IDEAL TO NOT HAVE THE LABEL BE ACCURATE FOR THE PRESCRIBING BEHAVIOR THAT'S HAPPENING. BUT IN BETWEEN THE TWO SIDES OF THE COIN THERE'S REALLY A SPECTRUM, AND WE HAVE TO WORK TOGETHER BECAUSE THERE'S NOT A CLEAR BOUNDARY BETWEEN THOSE. SO, CHRISTINE WILL LEAD THE PRE-CLINICAL SESSION THAT'S GOING TO HAPPEN IN THE MORNING. AND WE'LL COVER FROM INTRAMURAL WHO HAS EXPERIENCE IN REPURPOSING, WHAT SORT OF REGULATORY STUDIES ARE NEEDED. SO ONE CHALLENGE IS THERE ISN'T ANY REGULATORY GUIDANCE FOR REPURPOSING DRUGS, SO SOMETIMES PEOPLE ARE TRYING TO FOLLOW NOVEL CHEMICAL ENTITIES GUIDELINES, THAT'S NOT REALLY APPROPRIATE FOR SOMETHING THAT HAS A LOT OF HUMAN DATA. SO WE'RE GOING TO TACKLE THE QUESTION FROM FDA'S PERSPECTIVE WHAT ARE THEY WILLING TO SEE IN HUMAN STUDIES FOR A DRUG THAT HAS ABUNDANCE OF HUMAN DATA AVAILABLE. AND THEN WE'RE GOING TO TALK ABOUT THE TRANSITION BETWEEN WHEN REGULATORY STUDIES ARE NEEDED AT THE LATE STAGE TRANSLATIONAL SCIENCE TO ACTUALLY GETTING INTO THE CLINIC. SO ANOTHER CHALLENGE FOR PEOPLE WHO WANT TO DO THIS IS THE DATA MAY NOT BE ACCESSIBLE TO THEM, IT'S EITHER OPENED BY THE COMPANY OR FDA HAS IT BUT IT'S CONFIDENTIAL. SO IT COULD BE VERY EXPENSIVE TO HAVE TO REPEAT STUDIES JUST BECAUSE THE DATA ISN'T ACCESSIBLE. AND THEN THE NEXT QUESTION WE'RE GOING TO ADDRESS IS WHAT IS AN APPROPRIATE COMPARATOR, NOT ALWAYS APPROPRIATE TO DO PLACEBO CONTROLLED CLINICAL TRIAL SO WE'LL DISCUSS WHAT THAT STUDY DESIGN SHOULD LOOK LIKE. AND THEN WE'LL GET INTO THE CLINICAL EXPERIENCE SPECTRUM, WE'RE GETTING A LOT OF INPUT FROM FDA ON THIS. PARTICULARLY HEATHER STONE WORKED WITH INTRAMURAL ON APP THAT GETS INTO THE SPACE OF REAL WORLD EVIDENCE, REAL WORD DATA, HOW CAN WE USE EXISTING DATA TO WHAT IS THE PATHWAY FOR REGULATORY APPROVAL, HOW CAN THAT TYPE OF DATA BE USED TO UPDATE DRUG LABELS SO THEY ARE ACCURATE FOR HOW THE DRUGS ARE BEING USED CLINICALLY. AND THEN WE'RE GOING TO GO INTO SOME OVERARCHING ISSUES. SO UNDERLYING THIS PROBLEM THERE'S A LOT OF ECONOMIC ISSUES, AND YOU'LL ALSO NEED TO CONSIDER WHAT PAYERS ARE GOING TO BE WILLING TO DO, WHICH MAY NOT ALWAYS MIRROR REGULATORY PERSPECTIVE BUT WE NEED TO HAVE ALL THE PERSPECTIVES PRESENTED. SO THEN ON DECEMBER 6 WE'LL COME BACK AND WE'RE STILL WORKING ON THESE BREAKOUT GROUPS WITH CAN REVIEW BOARD DISCUSSION, THE DAY 1 IS MORE FLESHED OUT THAN DAY 2. BUT SO SINCE NOBODY OWNS THESE PROBLEMS, HOW ARE WE GOING TO DO SOMETHING ABOUT IT IS THE BIG QUESTION, AND THEN WHERE SHOULD FUNDING COME FROM, NCATS CAN'T FUND ALL THE NEED THAT'S OUT THERE FOR GENERIC REPURPOSING SO HOW CAN WE WORK TOGETHER WITH ALL THE STAKEHOLDERS, WHAT SHOULD OUR PRIORITIES BE TO FOCUS ON IN GAPS AND SUPPORT? WE'VE ALWAYS HAD AN INTEREST IN THIS BUT IT'S AN A CHALLENGE TO FIGURE OUT WHAT TO WE OWN, WHAT FITS INTO OUR MISSION. AND THEN NEXT WHAT INCENTIVES COULD BE PROVIDED TO ENCOURAGE GREATER PARTICIPATION FOR DRUGS WITH LIMITED PATENT LIFE AND REGULATORY EXCLUSIVITY. ARE THERE ANY PRIORITIES FOR DRUGS OR DISEASES THAT WE SHOULD FOCUS ON? AND THEN STEVE GRAPH SUGGESTED WHAT CAN WE LEARN FROM HISTORICAL ATTEMPTS TO FIX SIMILAR PROBLEMS, AND THEN OF THE DISCUSSION ABOUT USES OF REAL WORLD EVIDENCE TO SUPPORT SUPPLEMENTAL OR EXPANDED LABELING. I'D BE HAPPY TO ANSWER ANY QUESTIONS. >> THANKS, BOBBIE. >> THANKS TO RON, ANN AND BOBBIE ANN. SO THANKS FOR THAT. AND JUST QUICKLY, BEFORE WE GO INTO THE NEXT SESSION, ANY PARTICULAR QUESTIONS ABOUT WHERE WE'RE HEADING IN THIS? I THINK THE VISUAL OF ICEBERGS MOVING IN DYNAMIC FASHION AS BARRIERS TO BOTH OF THESE PROJECTS PRETTY EASY TO SEE, THERE ARE HUGE CHALLENGES, BUT IF WE CAN MAKE PROGRESS IN THIS YOU CAN SEE READILY HOW THAT WOULD CONNECT WITH THE ACCELERATING CURES MISSION OF THE CAN REVIEW BOARD AND NCATS IN GENERAL. ALL RIGHT. GO AHEAD, I'M SORRY. >> ON THE REPURPOSED INITIATIVES WHAT WOULD YOU CONSIDER SUCCESS FROM THE POINT OF VIEW OF NCATS? I THINK THE AGENDA YOU SET OUT IS TERRIFIC. AS YOU POINT OUT, IT IS A DIFFICULT PROBLEM. FROM YOUR PERSPECTIVE WHAT WOULD YOU CONSIDER SUCCESS, IF NOT AFTER THIS WORKSHOP, YOU KNOW, 12 MONTHS FROM NOW? >> I THINK THIS IS GOING TO HAVE TO BE A SERIES OF WORKSHOPS, THE FIRST WILL BE MAKING AN EDUCATIONAL RESOURCE AVAILABLE SO EVERYONE'S ON THE SAME PAGE OF WHAT THE ISSUES ARE. THAT'S NECESSARY IN ORDER FOR TO US HAVE INFORMATIVE DISCUSSIONS ABOUT HOW WE CAN SOLVE THE PROBLEMS. I THINK WE CAN -- THERE'S SO MANY TOPICS TO COVER IN TWO DAYS THAT WE CAN ONLY JUST TOUCH ON THE SURFACE ISSUES IN THE FIRST WORKSHOP AND WHATEVER COMES FROM THE DAY 2 BREAKOUTS I'M SURE WILL LEAD TO SUBSEQUENT WORKSHOPS. >> HOWEVER, IF I MAY ADD TO ELIZABETH'S POINT, THE QUESTION AROUND ECONOMIC BASIS OF EVALUATING PUBLIC IMPACT ARE PERTINENT AND WE HAVE TO TOUCH ON IT. THE PLANNING TEAM HAS CONSIDERED THAT BECAUSE RIGHT NOW WHEN WE DISCUSS WORKSHOP AND IMPACT, REAL WORLD EVIDENCE, EVEN STARTING WITH RELATIVELY SIMPLE AND STRAIGHT FORWARD THINGS LIKE POST MARKET SAFETY REGISTRIES, NETWORKS, AND THE ADVANTAGES AND BENEFITS, THE ECONOMISTS DON'T ALL AGREE ABOUT WHICH BAROMETERS ARE ACTUALLY GOING TO INCLUDE. AND AT THE END, AFTER ALL WE EVALUATE MEDICAL PRODUCTS, THAT ENHANCE PEOPLE'S LIVES, JUST LIKE CONSUMER PRODUCTS WHICH CERTAINLY IS NOT AN APPROACH WE SHOULD TAKE AS A SOCIETY, PARTICULARLY NOT AS A MODERN SOCIETY. SO I THINK TO HAVE A COMPONENT IN THE DISCUSSION AROUND THE ECONOMY OF THINGS IS VERY CRITICAL BECAUSE AT THE END SOMEBODY HAS TO PAY FOR IT. >> THE OTHER WAY I WOULD ANSWER LIZ'S QUESTION, THE HOPE IS THAT THIS WILL RESULT IN EVENTUALLY AN INITIATIVE, A FUNDING INITIATIVE FROM "CAN." BUT WE REALIZE THIS IS -- IT'S LIKE SO MANY OTHER PROBLEMS WE DEAL WITH. IT'S A MULTI-STEP ORGANIC SYNTHESIS WITH LIMITING STEPS. THE QUESTION IS WHICH ONE SHOULD WE START WITH, AND TO DEVELOP MAYBE A CATALYST FOR THAT ONE PROBLEM, AND FUND THAT, SO I'M THINKING ABOUT THIS VERY MUCH THE WAY THE GENE THERAPY ONE WENT, BECAUSE YOU JUST HEARD FROM RON THAT THERE'S A LIST -- THOSE ARE THE RATE-LIMITING STEPS FOR GENE THERAPY ACCORDING TO THE DUE DILIGENCE THAT HAS BEEN DONE. SO WE WOULD LOVE A SIMILAR LIST, AND THEN TO SAY, OKAY, WHAT ARE WE GOING TO ACTUALLY DO? AND THE IDEA, MY CONCEPT ABOUT THIS, THE SAME THING AS EVERYBODY NCATS DONE, WE WOULD HAVE A HYPOTHESIS, IF WE DEVELOP A NEW WAY TO DO SOMETHING AND WE CAN -- IT'S GOING TO BE A COLLABORATION, RIGHT? WITH MULTIPLE PEOPLE AND DEMONSTRATE USE CASE IT ACTUALLY WORKS, AND IF IT DOES, THEN DISSEMINATE THE WHOLE COMMUNITY, TEACH THE WHOLE COMMUNITY HOW TO DO IT. BUT RIGHT NOW, THERE ARE SO MANY PROBLEMS IN THIS SPACE THAT WHENEVER WE TALK ABOUT IT, WE ALWAYS HAVE SOMEBODY SAYING, YEAH, BUT, YOU KNOW, YOU CAN GET TO THAT POINT. YEAH, BUT, YOU'RE STILL GOING TO GET STUCK BECAUSE IT'S ANOTHER ICEBERG. WE FELT LIKE WE NEEDED TO DO AN ICEBERG INVENTORY AND THEN PICK OUT WHICH ICEBERGS MAY BE SMALLEST, BUT THE INTENT IS THAT MAN OVER THERE, AND YOU GUYS, THERE'S A BUDGET, RIGHT? THE QUESTION IS HOW TO USE THAT. >> AND I DO THINK THE IDEA OF A DEMONSTRATION PROJECT REALLY IS A GOOD ONE. >> YEAH. >> BECAUSE DIFFERENT FROM GENE THERAPY WHERE LOTS AND LOTS OF PEOPLE ARE WORKING ON IT. REALLY USING THIS TO ADVANCE THE FIELD, IT'S BEEN A LOT MORE DIFFICULT. REPURPOSEING PARTLY BECAUSE OF ECONOMIC CHALLENGES, AS YOU POINT OUT. >> I ALSO DON'T THINK THE ONLY OUTCOME WILL BE WHAT NCATS WILL FUND. I THINK IT'S MORE LIKELY THAT MULTIPLE STAKEHOLDER ORGANIZATIONS FORM A COLLABORATION AND PRIORITIZE WHO CAN SOLVE WHICH PROBLEMS >> YEAH, THAT'S WHERE I WAS GOING TO GO AS WELL. WE HAVE EXPERTISE IN TEAM SCIENCE. WE HEARD EARLIER THIS IS DEFINITELY TEAM PLAY. THERE MAY BE A ROLE FOR NCATS, THERE MAY BE A ROLE FOR OTHER PEOPLE TO BE INVOLVED AND ENGAGE. >> SO JUST PLAYING OFF THE ECONOMIC COMPONENT AGAIN, IT WOULD BE INTERESTING TO UNDERSTAND THE ECONOMICS OF ACTUALLY DEVELOPING A REPURPOSED DRUG BECAUSE MY GUESS IS IT'S FRACTIONAL OF AN NCE. SO FROM A MANUFACTURING PERSPECTIVE, YOU'VE ALREADY GOT THE SYNTHESIS. THERE'S A LOT THAT YOU KNOW ABOUT IT. THERE MAY BE DEPENDING ON IF YOU'RE GOING UP IN DOSE, OR LONGER IN DURATION, YOU MAY NEED ADDITIONAL TOXICOLOGY STUDIES, BUT MAYBE NOT. AND THEN IT WOULD BE INTERESTING AND BEING A BIT PROVOCATIVE HERE, WHAT IF YOU NEVER REGISTERED IT? I MEAN, IF IT'S A CURRENT DOSE. YOU KNOW, DO YOU NEED A -- IF THERE'S MULTIPLE COMPANIES MAKING T DO YOU ACTUALLY NEED TO GET IT ON THE LABEL, BECAUSE SO MANY DRUGS THAT ARE PRESCRIBED TODAY ARE OFF LABEL, APOLOGIES TO. >> 50% OF THE DRUGS ARE USED OFF LABEL, FOR THE RECORD. >> SO IT'S SOMETHING TO THINK ABOUT FROM A RISK/BENEFIT, COST-BENEFIT PERSPECTIVE THAT THERE ISN'T NECESSARILY A ONE-SIZE-FITS-ALL. SO I DON'T KNOW WHAT IT COSTS TO REPURPOSE A DRUG. I KNOW IT'S INDICATION DEPENDENT, OF COURSE, BUT MY GUESS IS WHEN YOU READ SOME OF THE $2 BILLION, $3 BILLION, YOU KNOW, FOR A DRUG, THAT'S LIKE EVERYTHING PUT TOGETHER. IF YOU TAKE A REPURPOSE DRUG, THE COSTS COULD BE A SMALL FRACTION OF THAT. THAT MIGHT BE AN IMPORTANT MESSAGE IN AND OF ITSELF. >> SO BUT AGAIN TO HIGHLIGHT, I THINK THAT'S THE COST AND REASON WHY NCATS AND "CAN" PICKED THIS UP, BECAUSE THE CURRENT ECONOMIC EVALUATION OR VALUATION ISN'T QUITE SUPPORTIVE OF GETTING GENERICS INTO AN EXTENDED SPACE PATIENTS WOULD HAVE REAL ACCESS UNLESS IT'S AN AGREEMENT BETWEEN THE PROVIDER, THE PHYSICIAN AND PATIENT, NAMELY THE OFF-LABEL USE. WHAT WE'RE INTERESTED IN AS A PUBLIC IS SHOW AND DEMONSTRATE FIRST OF ALL WE BENEFIT ALL IF YOU UNDERSTAND THE SAFETY AND EFFECTIVENESS OF THOSE DRUGS USED OFF LABEL MUCH BETTER AND EXPAND PUBLIC HEALTH IMPACT BY INCLUDING OTHER ECONOMIC CONSIDERATIONS, AND I THINK THAT'S ONE OF THE HINGING POINTS THAT WE HAVE TO WORK TOWARD BECAUSE OTHERWISE WE'LL CONTINUE TO NOT GET THEM THERE WHEN WE NEED THEM >> SO AT THE RISK OF US STARTING OUR DECEMBER 5 AND 6 WORKSHOP TODAY, MAYBE WE'LL -- [LAUGHTER] -- WE'LL TRANSITION. IT IS GOOD TO SEE THE ENTHUSIASM FOR THE TOPIC. AND FINAL WORD ON THIS, GOING BACK TO WHY I SHOW THE LITTLE CHART AT THE BEGINNING, PEOPLE WANT TO LEAP TO PUTTING OUT FUNDING A PROPOSAL AND, YOU KNOW, HAVING SOLICITATIONS, MAKING AWARDS. THE PREPARATION NECESSARY IN BOTH SPACES IS TRULY IMPORTANT, SO THAT WE FUND IN THE APPROPRIATE WAY TO HAVE A MEASURABLE TANGIBLE OUTCOME AT THE END THAT MOVES THE SPACE FORWARD RATHER THAN JUST TRYING TO SHOVE DOLLARS OUT THE DOOR. ALL RIGHTY. AND LAST ON THE CAN REVIEW BOARD DISCUSSION LEVERAGING CAN AUTHORITY. SO AS I MENTIONED, NCATS MANAGEMENT JONI, ANNA, CHRIS, AND THEY WERE TALKING TO US, SO THIS IS A CONVERSATION FROM THEM TO THE CAN REVIEW BOARD IN TERMS OF AN AREA WHERE WE COULD POTENTIALLY ESTABLISH A WORKING GROUP THAT COULD HELP ADVANCE THE MISSION OVERALL. SO, THE QUESTION REGARDS THE EVOLUTION OF THE CAN REVIEW BOARD TO SUPPORT THE MATURATION OF "CAN" PROGRAMS AND ACTIVITIES. CAN WE LOOK BACK -- RON MENTIONED AS A SEGUE ABOUT HAVING UNIQUE AUTHORITIES OR DIFFERENT AREAS OF THE GOVERNMENT, HAVE DIFFERENT AUTHORITIES, AND THE QUESTION IS, HOW CAN NCATS EMPLOY THE "CAN" AUTHORITIES BETTER TO HASTEN ADOPTION OF CUTTING-EDGE SCIENCE THAT IT FOSTERS? DRILLING DOWN A LITTLE BIT MORE ON THAT, WHAT I WOULD LIKE FOR US TO COME BACK AT THE END OF THIS DISCUSSION IS ARE WE INTEREST IN RESPONDING TO THIS NCATS REQUEST, TO LEVERAGE THE POWER OF OUR AUTHORITIES SO THE AREAS DOWN AT THE BOTTOM ARE IN GENERAL AREAS WHERE WE COULD FOCUS ON THAT MAY NOT BE THE ENTIRE LIST, IT MAY BE WE PRIORITIZED SOMETHING DIFFERENTLY BUT THE REAL CONVERSATION HOW DO WE RESPOND AND REACT TO NCATS REQUEST FOR THE CAN REVIEW BOARD TO LOOK INTO THESE TOPICS. IF WE TAKE THE FOUR DOWN AT THE BOTTOM, REVIEW AND ASSESS CAN AUTHORITY TO BETTER LEVERAGE EXISTING AUTHORITIES, POTENTIALLY IDENTIFY ADDITIONAL AUTHORITIES THAT WE NEED TO ENSURE NCATS IS USING ITS FULL POWER FOR ADVANCING AND ACCELERATING TRANSLATIONAL SCIENCES INTO IMPLEMENTATION. AND THEN THE PROJECT PRIORITIZATION AND SUNSETTING, ARE WE DOING THAT IN THE OPTICAL MAY? WE USED TISSUE CHIPS WITH DAN AND THE TEAM DOING TO THAT ARE YEARS. LOTS TO BE PROUD OF. ARE WE OPTIMALLY HAVING OUR PROGRAMS COME FORWARD AND HANDING THEM OFF TO THE OTHER OTHER STAKEHOLDERS, I.C.s, FOCUS GROUPS, DID WE DO ENOUGH? HOW DO WE KEEP TOUCH WHERE WE COME IN AND HELP NEW ISSUE THAT MIGHT ARISE LATER THAT THEY COME BACK WITH THAT MIGHT BE UNIVERSALLY APPLIED ACROSS DISEASE AREAS? THEN OUR LONG-TERM SUSTAINABILITY, IDENTIFYING FACTORS THAT FACILITATE TRANSITION, ADOPTS, ADAPTATION, SORRY, INTO THE REAL WORLD SO WE DON'T JUST HAVE A PUBLICATION AND THAT'S IT. WE ACTUALLY HAVE THESE OUTPUTS THAT ARE PART OF HOW WE MANAGE PATIENTS AND HOW WE IMPROVE HEALTH AROUND THE COUNTRY AND ARGUABLY AROUND THE WORLD BECAUSE OF THE IMPACT THAT WE CAN HAVE. AND ENGAGING STAKEHOLDERS, FACTORS TO ENHANCE STAKEHOLDER ENGAGEMENT, LOWER BEARSERS TO TRANSLATIONAL RESEARCH ACROSS MANY SECTORS, SOME GROUPS HAVE -- I DON'T KNOW ABOUT ADVISORY, WHAT ARE THEY CALLED, CHRIS? STAKEHOLDER GROUPS THAT COME IN AND ADVOCATE ON BEHALF OF AN SO, YOU KNOW, ARE WE OPTIMALLY USING THE CAN REVIEW BOARD AS AN AVENUE TO MAKE SURE THAT WE UNDERSTAND WHAT OTHERS THINK, PROVIDING COVERAGE AND LEVERAGE TO NCATS IN TERMS OF GOOD THINGS THEY ARE DOING, RATIONALES AND STRATEGIES, HOW ARE WE DOING THAT AND CAN WE OPTIMALLY DO IT. AND I DID WANT TO CALL ON JONI, JUST TO MAKE SURE THAT WE'RE HEARING WHAT NCATS IS ASKING AND ANYTHING ELSE YOU WOULD LIKE TO ADD AS AN EXAMPLE OF THE KIND OF THINGS WE COULD WORK ON. >> THANKS, LYNN. THAT WAS A BEAUTIFUL CONCEPTUALIZATION OF WHAT WE HAD DISCUSSED. I'LL JUST ADD THAT I THINK IT WAS 2012 WHEN THERE WAS AN IOM REPORT ON HOW TO MAXIMIZE THE IMPACT OF THE CURES ACCELERATION NETWORK, AND THAT WAS REALLY -- THAT MEETING WAS JUST AFTER THE LEGISLATION WAS IN PLACE, AND IT WAS REALLY FOCUSED ON HOW WE CAN BRING OPPORTUNITIES INTO NCATS AND BRING THE CAN REVIEW BOARD TO HELP US IDENTIFY AND CREATE THEM. AND WE'VE DONE SUCH I THINK AN INCREDIBLE JOB WITH THE EXAMPLES OF THE PROJECTS THAT WE HAVE IN "CAN," THAT ARE NOW STARTING TO BECOME MORE AND MORE MATURE, AND SO THIS IDEA OF REALLY FOCUSING NOW ON THE BACK END OF THOSE AUTHORITES AND HOW THE CAN REVIEW BOARD CAN HELP US ENSURE THAT WE'RE THINKING ABOUT THE STAKEHOLDERS FROM THE VERY BEGINNING OR ALONG THE WAY WAY AND IDENTIFYING THOSE APPROPRIATELY MAY BE DIFFERENT, SOME MAY BE THE SAME, TO IDENTIFY STAKEHOLDERS AND MOVE THE PROJECTS FORWARD. I THINK THAT'S REALLY WHERE WE'RE TRYING TO GET AT. THE ONLY OTHER THING I MIGHT ADD IS AS YOU THINK ABOUT THIS IDEA, I WOULD ENCOURAGE YOU TO THINK OF A PROCESS OF SEVERAL DISCUSSIONS TAKING PLACE OVER THE NEXT NINE MONTHS TO A YEAR, FOR EXAMPLE, AND PUTTING SOMETHING TOGETHER THAT WOULD START TO DO A DEEP DIVE AGAIN ON THE "CAN" AUTHORITIES AND BEGIN TO THINK ABOUT THE PROJECTS THAT WE HAVE IN PLACE AND PERHAPS HAVE PRESENTATIONS FROM, FOR EXAMPLE, THE TISSUE CHIP PROGRAM FROM PERSPECTIVE OF HOW IT BEGAN, AND HOW IT'S GOING AND HOW IT'S STARTING TO MATURE AND THEN THE OTHER PROJECTS AS WELL. BUT ALSO TAKE A LOOK AT HOW WE'VE HANDLED THE BUDGET AND POLICIES ALONG THE WAY FOR THOSE PROJECTS. SO I SEE THIS HAPPENING OVER THE NEXT ROUNDS OF CAN REVIEW BOARD ACTIVITIES AND NCATS ADVISORY COUNCIL MEETINGS. AND USING THIS AS A SUBSEQUENT WAY OF MEETING AND CONVENING TO TALK ABOUT THESE ISSUES BEFORE PROVIDING SOME RECOMMENDATIONS TO CHRIS AND NCATS, HOW WE COULD IMPLEMENT THEM. SO THAT'S WHAT I WOULD PROPOSE THERE, JUST ADDING ON TO WHAT LYNN REMARKED. >> FOR EXAMPLE WE MIGHT COME BACK AT OUR DECEMBER MEETING AND LOOK AT EACH OF THE PROGRAMS TO SEE HOW THEY ARE BEING IMPLEMENTED. WE JUST TALKED ABOUT HOW DO WE GET THESE INTO THE REAL WORLD, AND ARE WE OPTIMALLY DOING THAT ONBOARDING, OFFBOARDING, USING OUR AUTHORITIES, ET CETERA. WE COULD START IN DECEMBER BY UNDERSTANDING WHERE WE ARE WITH EACH OF THE "CAN" REVIEW BOARD PROJECTS, AND THEN COME BACK AND FIGURE OUT WHERE WE WANT TO GO FROM THERE, NEXT STEPS. I'LL PAUSE HERE TO SEE WHAT QUESTIONS FOR CLARIFICATION TO NCATS, TO JONI OR CHRIS OR ANNA, IN TERMS OF WHAT THEY ARE ASKING US TO DO AND WOULD WE AGREE THAT WE WOULD LIKE TO HELP THEM WITH THIS REQUEST, OR WE DON'T WANT TO BOTHER, HOW DO WE FEEL ABOUT THAT AS A CAN REVIEW BOARD? >> SO I THINK THIS IS A REALLY TIMELY AND IMPORTANT TOPIC, AND INITIATIVE TO GRAB HOLD OF. I THINK IF YOU THINK OF THE BIG PICTURE AND MISSION OF NCATS TO TRANSFORM TRANSLATION, YOU KNOW, A LOT OF THESE GREAT IDEAS NEED TO REALLY PENETRATE THE BROADER COMMUNITY AND REALLY HAVE CHAMPIONS THAT TAKE THEM IN AND REALLY CHANGE PRACTICE IF WE'RE GOING TO SEE THE IMPACT WE HOPE TO SEE AND PROMISE AND TECHNOLOGY. I THINK WE WATCH SOME OF THESE PROGRAMS MATURE, WE WATCH THE GREAT TECHNOLOGICAL DEVELOPMENT THAT OCCURRED, WHICH IS IS, OKAY, WILL IT WORK, WILL ITN MAKE A DIFFERENCE? AND I THINK IT'S A GREAT EXAMPLE TO HAVE INTRAMURAL PROGRAMS TAKE THESE ON AND BEGIN TO GENERATE SOME PRACTICE, THAT HAS TO BE SHARED AND DISSEMINATED AS YOU TALKED ABOUT BUT I REALLY THINK THAT ANY NEW TECHNOLOGY REALLY REQUIRES A VERY STRONG FORWARD STRATEGY FOR ADOPTION OF BROADER COMMUNITY, YOU KNOW, WHETHER YOU'RE WITHIN A COMPANY TRYING TO MAKE CHANGE OR TRYING TO MAKE A CHANGE THROUGH NCATS, THERE'S ALWAYS CULTURAL BARRIERS AND INITIAL DISMISSIVENESS, WHILE THIS IS THE WAY WE DO THINGS, YOU KNOW, THIS IS THE WAY WE'RE GOING TO CONTINUE, SHOW ME THAT IT'S BETTER. IT'S AN OBLIGATION TO REALLY BE A TEACHER BUT ALSO REALLY PROVIDE A PATHWAY FOR INDIVIDUAL COLLECTIVE LEARNING THAT, HEY, IN THESE CONTEXTUAL SITUATIONS, MORE SPECIFICALLY OR GENERALLY, THIS REALLY ADDS ADVANTAGE, INCREASING EFFICIENCY, REDUCES TIME, GIVES MORE INFORMATION, IMPROVES THE TRANSLATIONAL PREDICTION. I THINK ALL THOSE THINGS REALLY NEED TO BE MAPPED OUT VERY NICELY SO PEOPLE CAN CONNECT AND UNDERSTAND HOW THIS CAN TRANSFORM THEIR BUSINESS PRACTICE, AND SO ONE IS JUST PUTTING IT OUT THERE, HOPING THAT IT JUST HAPPENS ORGANICALLY BUT I THINK FOR SOME OF THESE INITIATIVES, VERY STRONG INVESTMENT, GREAT TECHNOLOGY BEHIND THEM, A LOT OF POTENTIAL, I THINK THERE HAS TO BE MORE OF A DETERMINISTIC DRIVE AND MAYBE THROUGH THESE EXPANDED POWERS AND PLANNING THERE CAN BE SOME GREAT EXAMPLES OF HOW TO MAKE THAT MORE TANGIBLE AND FIND WAYS FOR GROUPS TO CONNECT AND MAYBE EDUCATE BUT ALSO LOWER BARRIERS FOR ADOPTION >> ANYPLACE ELSE? >> YEAH, I WAS THINKING ALONG THE SAME LINES. THAT, HOW DO YOU TAKE SOMETHING THAT'S INNOVATIVE AND INCREASE ADOPTION OF THAT? IF I THINK ABOUT SOME OF THE WORK IN THE CLINICAL TRIALS AREA, IN THE INNOVATIONS THAT WERE DONE THERE, EVEN COMMON SENSE THINGS AROUND IRBs AND SOME OF THOSE TYPES OF THINGS, ARE REALLY INNOVATIVE AND THEY SPEED UP THINGS. SO IT WOULD BE INTERESTING TO THINK OF IF YOU DID SOMETHING OTHER THAN PUBLISH AND/OR A WORKSHOP, WHAT ELSE COULD YOU DO TO DRIVE ADOPTION? THAT MAY BE AN INTERESTING AREA FOR NCATS TO TAKE SOME OF ITS INNOVATIVE FIBERS AND TRY TO THINK ABOUT HOW TO ACTUALLY ACCELERATE SINCE THAT'S ONE OF THE WORDS THAT'S? THE ACRONYM, HOW TO ACCELERATE IN INNOVATIVE WAYS THE REALLY FANTASTIC IDEAS THAT ARE BEING IMPLEMENTED OR HAVE BEEN DISCOVERED. >> OTHER COMMENTS, QUESTIONS, CLARIFICATIONS? >> WELL, ACTUALLY THOSE ARE REALLY CRITICAL QUESTIONS THAT THE V.A. HAS ASKING, PARTICULARLY WITHIN HEALTH SERVICES RESEARCH ARENA. WE HAVE, AS YOU KNOW, A NUMBER OF REALLY GREAT RESEARCHERS. THEY HAVE PUT OUT LOTS AND LOTS OF EFFECTIVE INTERVENTIONS AND TOOL KITS. WE'RE FINDING OUT THAT THOSE INTERVENTIONS OFTEN DO NOT GET ACCEPTED, EVEN WITHIN THE V.A. AND WE RUN INTRAMURAL RESEARCH DONE BY CLINICAL RESEARCHERS WHO ARE PART OF THE V.A. AND WE HAVE TO ASK, WE HAVE TO MAKE A PARADIGM SHIFT IN TERMS OF THE RFAs, THE AWARDS THAT WE PUT OUT, AND ONE THING THAT JUST -- WE JUST HAVE REQUIRED NOW, IN ALL OF OUR SOLICITATION, IS TO PARTNER AT THE VERY BEGINNING, RESEARCHERS HAVE TO PARTNER WITH THE POLICYMAKERS, AND POLICYMAKERS WITHIN THE V.A. ARE PROGRAM OPERATIONS FOLKS. OFTENTIMES WHAT HAPPENS IS YOU HAVE A WONDERFUL -- WE'VE INVESTED FIVE, SIX, SEVEN YEARS OF FUNDS FOR AN EFFECTIVE INTERVENTION AND THEN WE GO TO THE OPERATIONS FOLKS AND THEY CAN'T TAKE IT. THEY CAN'T ADOPT IT, BECAUSE IT WOULD REQUIRE ADDITIONAL STAFF TO BE HIRED, CHANGES IN THE INFRASTRUCTURE, THE PROCESSES, HOW THEY DO CLINICAL, YOU KNOW, SERVICES. SO, THAT'S ONE OF THE THINGS THAT WE HAVE REQUIRED THAT YOU HAVE TO -- THIS IS SIMPLE -- TALK WITH PEOPLE WHO ARE YOUR POLICYMAKERS FROM THE VERY BEGINNING. AND THE OTHER THING WE HAVE MADE CHANGES TO, WITHIN OUR CLINICAL -- WHAT WE CALL OUR TRIALS PROGRAM, COOPERATIVE AGREEMENT, WE'VE REQUIRED -- WE'RE NOW REQUIRING ALL OF OUR INVESTIGATORS TO INCLUDE IN THEIR TRIAL DESIGN AN IMPLEMENTATION PLAN. œTHEY HAVE TO REALIZE THEINNING, ULTIMATE GOAL OF WHAT THEY ARE DOING, AND IT'S NOT JUST TO GET PUBLICATIONS IN PREMIER JOURNALS BUT IT HAS TO GO OUT INTO THE REAL WORLD. AND AMONG THE V.A., I OFFICIALLY THOUGHT NAIVELY THAT IT'S EASY TO IMPLEMENT AND HAVE 172 OF OUR HOSPITAL MEDICAL CENTER PROVIDERS JUST UP AND TAKE IT, AND THAT IS NOT THE CASE. >> ALL RIGHT. WELL, I THINK I'M FEELING POSITIVE SENTIMENT. WE WEREN'T PLANNING ON HAVING A FORMAL VOTE. RON AND I BELIEVE THE CAN REVIEW BOARD SHOULD SPONT TO NCATS REQUEST AND WE ONLY HAVE ONE -- RESPOND TO NCATS REQUEST AND WE ONLY HAVE ONE NON-NEGOTIABLE, WOULD LOVE TO PARTNER WITH YOU, JONI, DO MAKE SURE WE'RE CONNECTING IN THE RIGHT WAY AND ADDRESSING THE QUESTIONS, IF THAT'S OKAY. WE'LL BRING MORE OF THIS INFORMATION TO THE DECEMBER CAN REVIEW BOARD MEETING AND FOR THOSE NOT CAN REVIEW BOARD MEMBERS, OTHER STAKE HOLDERS WHO HAVE AN INTEREST, THIS IS NOT MEANT TO BE EXCLUSIONARY AT ALL IN TERMS OF TRYING TO UNDERSTAND HOW BEST WE CAN HELP NCATS AND OUR COLLECTIVE MISSIONS. SO WITH THAT, ANNA -- >> FIRST I WANT TO THANK YOU FOR ACCEPTING THE CHALLENGE, AND WHEN WE WERE THINKING ABOUT THIS INTERNALLY WE THOUGHT, GOSH, WHO BETTER TO HELP US WITH THIS PROBLEM THAN THIS GROUP? IF YOU LOOK AT THE ORGANIZATIONS AROUND THE TABLE, GATES DEALS WITH THIS QUESTION EVERY SINGLE DAY, V.A. DEALS WITH IT EVERY SINGLE DAY, THE FDA DOES FROM THEIR POINT OF VIEW, ET CETERA, AND THE PATIENT GROUPS OF COURSE WITH THE "WHERE'S THE BEEF" PEOPLE. MEDTRONIC, ALL THE PRIVATE EQUITY FOLKS, THESE ARE ALL FOLKS WHO ARE IN THIS WORLD, THAT ARE "SO WHAT" PEOPLE, AND SO YOU'VE DONE THIS GREAT PUBLICATION, SO WHAT? SO, WE REALLY APPRECIATE YOUR THINKING HARD ABOUT THIS, ABOUT WHAT WE SHOULD DO FROM THE STANDPOINT OF THE CAN BOARD AND ITS AUTHORITIES, SOME OF WHICH WE HAVEN'T EVER USED, TO MAKE THIS HAPPEN. SO WE REALLY APPRECIATE YOUR THINKING HARD ABOUT THIS AND GIVING US AS DISRUPTIVE SUGGESTIONS AS YOU WOULD LIKE, BECAUSE WE REALIZE IT'S A HARD PROBLEM. SO WE'RE REALLY INTERESTED IN UNION IF , YOU KNOW, IF YOU HAD YOUR DRUTHERS, WHAT WOULD YOU HAVE. >> SOUNDS LIKE A DEAL, CHRIS. ANNA, I'LL TURN IT OVER TO YOU. >> THAT'S IT. WE ARE DONE FOR THE PRE-LUNCH SESSION. I'LL HAVE LUNCH REMAIN -- ENDS AT 1:15, WE'LL COME BACK FOR THE ORDR PRESENTATION AT 1:15. THANK YOU. >> THIS AFTERNOON WILL BE AN UPDATE, IT MAY BE A DATE FOR ALL OF YOU, NOT AN UPDATE. IF YOU HAVEN'T HEARD ABOUT ORDR, WE'RE GOING TO TALK ABOUT ORDR, FOR THE NEXT HOUR OR SO, AND THEN AFTER THAT WE'RE GOING TO DO CONCEPT CLEARANCES, TWO THAT ARE STRAIGHTFORWARD COMPARED TO THE ONES WE DID LAST TIME. AND THEN A DISCUSSION I THINK YOU'LL FIND REALLY INTERESTING ON CLINICAL RESEARCH INFORMATICS THAT KEN GERSING WILL DO. ANNE WHY DON'T YOU START. >> GOOD AFTERNOON. I'M ANNE PARISSER, I'M HAPPY TO HAVE THE OPPORTUNITY TO SHARE THE WORK WE'VE BEEN DOING IN THE OFFICES OF RARE DISEASE RESEARCH WITH YOU. BRIEFLY, OUR MISSION LIKE THAT OF THE REST OF NCATS IS NOT WITH ANY ONE PARTICULAR RARE DISEASE BUT TRYING TO IMPROVE THE RESEARCH ENVIRONMENT FOR ALL RARE DISEASES. AND, FOR THOSE NOT AS FAMILIAR WITH RARE DISEASES, RARE DISEASE IN THE UNITED STATES IS DEFINED AS A DISEASE WITH A PREVALENCE OF LESS THAN 200 PEOPLE IN THE UNITED STATES. SO IN THE U.S. IS A KEY PHRASE LIKE MALARIA IS RARE IN THE UNITED STATES, WOULD ALSO QUALIFY. THERE ARE 7,000 OR SO DIFFERENT RARE DISEASE, WE DON'T KNOW THE EXACT NUMBER. BUT ONE THING TO NOTE IS THAT THE PREVALENCE IS HIGHLY SKEWED TOWARDS THE LOWER PREVALENCE DISORDERS, SO THIS IS PREVALENCE OF KNOWN DISORDERS, THIS IS FROM AN INSTITUTE OF MEDICINE REPORT ABOUT TEN YEARS AGO, SO WE HAVE A LOT MORE DISEASES SINCE THEN. BUT MOST DISEASES CLUSTER AT THE LOWER PREVALENCE, TRANSLATES TO PREVALENCE OF 175,000 PEOPLE BUT IF YOU BREAK THAT DOWN EVEN FURTHER, MOST OF THOSE DISEASES CLUSTER WAY DOWN HERE TO THE LESS THAN 350 TO LESS THAN 3500, AND WE DO HAVE ACTUALLY A LOT OF DISEASES THAT ARE EVEN LESS PREVALENT THAN THAT. YOU THAT UPPER LEVEL OF 200,000 ALMOST NEVER APPLIES, USUALLY TALKING ABOUT A LOT FEWER PATIENTS THAN THAT. THIS IS THE ORDR STAFF, MOST HERE, RAISE YOUR HANDS. TEN FULL TIME OF US, AND WE HAVE A CONSULTANT THAT WORKS HALFTIME. AND NOTABLY IS ABOUT HALF ARE NEW SINCE LAST TIME I STOOD AND TALKED HERE. WE HAVE A LOT OF NEW PEOPLE, A LOT OF NEW ENERGY, AND EXCITE THE. AND TO PUT ORDR TO NCATS PERSPECTIVE, HERE IS THE PIECHART OF THE NCATS BUDGET, AND ORDR IS THIS TINY RED PIECE RIGHT HERE. SO WE'RE ABOUT 3% OF THE NCATS BUDGET, AND THAT'S ABOUT $24 MILLION IN FISCAL YEAR 2019. AND JUST LOOKING OVER THE PAST SIX YEARS WE'VE STAYED RELATIVELY STEADY, 3% EVEN WITH THE LITTLE UPS AND DOWNS OF NCATS BUDGET. SO, LET'S TAKE A CLOSER LOOK HOW ORDR SPENDS ITS MONEY. HERE IS THE RED PIECE OF NCATS BUDGET, MOST OF OUR MONEY GOES TO THE RARE DISEASE CLINICAL RESEARCH NETWORK WHICH IS THIS BIG BLUE PIECE HERE, ABOUT 70%. NEXT BIGGEST PIECE IS THE GENETICS AND RARE DISEASES INFORMATION CENTER WHICH -- AND SEVERAL OTHER PROGRAMS WITH SMALLER AMOUNTS, AND I'LL BE GOING INTO THESE IN SOMEWHAT MORE DETAIL. ALSO NOTED AT THE BOTTOM WE'RE ALSO WORKING WITH ABOUT $4 MILLION IN "CAN" FUNDING THIS LAST FISCAL YEAR FOR THE PLATFORM FOR GENE THERAPY PROGRAM. THIS IS AN NCATS COLLABORATION BETWEEN ORDR AND DCI AND SEVERAL OTHERS. I'LL BE TALKING ABOUT THAT AS WELL. SO JUST A VERY BRIEF HISTORY OF HOW ORDR CAME TO BE IN JUST A FEW FACTS FOR WHY WE'RE CONCENTRATING IN SOME AREAS WE ARE, SO ORDR ACTUALLY STARTED IN 1989, AND WAS INITIALLY PART OF THE OFFICE OF THE DIRECTOR. AND ORPHAN DRUGS ALSO KNOWN -- ORPHAN DISEASES ALSO KNOWN AS RARE DISEASES WERE DEFINED FOR THE FIRST TIME IN 1983 THROUGH THE ORPHAN DRUG ACT. THIS WAS PRIMARILY DIRECTED TOWARDS FDA WHO THEN ESTABLISHED THE OFFICE OF ORPHAN PRODUCTS BUT THIS LED TO A NUMBER OF THINGS INCLUDING NATIONAL COMMISSION ON ORPHAN DISEASES WHICH RECOMMENDED THAT NIH ALSO STAND UP A RARE DISEASE OFFICE, AND DEVELOP A NATIONAL RESEARCH AGENDA FOR RARE DISEASES AND THIS IS WHERE ORDR INITIALLY CALLED OFFICE OF RARE DISEASES BEGAN. THIS WAS LATER -- LATER HAD ITS OWN ACT, RARE DISEASE ACT, IN 2002. AND BECAME THE OFFICE OF RARE DISEASES RESEARCH IN 2010 AND THEN MORE RECENTLY IN 2012 MOVED TO FISCAL YEAR 2012 WHEN NCATS WAS STOOD UP. DURING THAT TIME RARE DISEASES HAS CHANGED A LOT. SO HERE IS THE DIAGRAM I THINK CHRIS HAS SHOWN A NUMBER OF TIMES BUT DISORDERS WITH KNOWN MOLECULAR BASIS, 1989, HERE GOING FROM TEN OR SO DISEASES FOR WHICH MOLECULAR BASIS WAS KNOWN DOWN TO 6500, DNA ERA OF THE DRAMATIC INCREASES IN WHAT WE KNOW ABOUT THE GENOME HAS REALLY BEEN A BOON TO RARE DISEASES. ALSO SHOWING HERE, THIS IS IN ABOUT 1984 TO 2000, THE NUMBER OF HOUSEHOLDS AROUND -- IF YOU LOOK WHERE THE ARROW IS, AROUND 89, ONLY 15% OF HOUSE HOLDS HAD HOME COMPUTER, AND THIS GRAPHIC HERE IS ACTUALLY THE INTERNET. IT WAS IN 1992, IT WAS ACTUALLY MOSTLY A DEFENSE AND RESEARCH INTERNET, AND THESE ARE IMPORTANT FACTORS BECAUSE THEY WEIGH INTO THINGS WE RELY ON NOW, AND REALLY CHANGE THE RESEARCH AND TREATMENT LANDSCAPE FOR RARE DISEASES, SO AMAZING PROGRESS AND CHANGES IN THE 30 YEARS OF THE EXISTENCE OF THE OFFICE. AND HERE'S A RARE DISEASE ACT, HIGHLIGHTED A FEW THINGS IN HERE THAT WE ACTUALLY HAVE THREE CONGRESSIONAL MANDATES, SO PART OF THE RARE DISEASES ACT. THE ONE AT THE TOP, THIS ONE, IS TO PROVIDE A BROAD RANGE OF RARE DISEASE RESEARCH AND EDUCATION, THAT WAS THE CONFERENCE GRANTS PROGRAM WE TALKED ABOUT EARLIER. HERE IS NIH SHOULD ENTER INTO COOPERATIVE AGREEMENTS, MAKE GRANTS FOR REGIONAL CENTERS OF EXCELLENCE, THIS BECAME THE RARE DISEASES CLINICAL RESEARCH NETWORK. THE ONE AT THE BOTTOM THAT NIH WAS DIRECTED TO ESTABLISH WITH CLEARINGHOUSE FOR RARE AND GENETIC DISEASE INFORMATION THAT THEN BECAME THE GUARD GENETIC AND RARE DISEASE INFORMATION CENTER, GARD CENTER. CURRENTLY WE HAVE 7,000 DISEASES THAT WE ARE TRYING TO HELP, THERE'S ABOUT 200 TO 250 NEWLY RECOGNIZED RARE DISEASES EVERY YEAR, ONLY ABOUT 5% HAVE AN APPROVED THEY APPROVED THERAPEUTIC, IN THIS CONTEXT THIS ONE DISEASE AT A TIME PARADIGM IS WAY TOO SLOW. WE NEED TO CONSIDER OTHER APPROACHES SUCH AS MANY AS A TIME, PLATFORM APPROACHES WHICH WE'LL BE TALKING ABOUT, OR HOW TO MAKE SHARED MOLECULAR ENTITIES, SOME THINGS WE'LL BE TOUCHING ON. THIS IS JUST AN OVERVIEW OF OUR PROGRAMS, WHICH LARGELY FALL INTO THREE CATEGORIES, KNOWLEDGE AND DATA, RESEARCH COLLABORATION, AND COMMUNITY ENGAGEMENT. AND I'M GOING TO START TALKING ABOUT THE RARE DISEASE CLINICAL RESEARCH NETWORK. SO, WHAT IS RDCRN? NETWORK OF CENTERS OF EXCELLENCE, AND THEY ARE GROUPED AROUND DISEASE AREAS WHICH YOU'LL SEE IN A LITTLE BIT MORE ABOUT, AND WE'RE TRYING TO FACILITATE RARE DISEASE RESEARCH THROUGH ESTABLISHING THESE CONSORTIA, WE'RE TRYING TO HAVE MULTI-DISCIPLINARY TEAMS WORK CLOSELY TOGETHER, AND WE HELP TO BUILD INFRASTRUCTURE TO SUPPORT THIS RESEARCH. AND THIS IS TINA AND MIRA, THE PROGRAM LEADS FROM ORDR. SO JUST A BRIEF WORD, IT WAS ESTABLISHED IN 2002 UNDER RARE DISEASE ACT, FIRST CONSORTIA INITIATED IN 2003. AND THESE ARE FIVE-YEAR AWARD CYCLES, SO WE'RE JUST FINISHING OFF THAT THIRD FIVE-YEAR COHORT WHICH WAS KNOWN AS RDCR 3, JUST STARTING THE FOURTH CYCLE, RDCRN 4. THIS IS ALSO A COLLABORATION WITH OTHER NIH INSTITUTES AND CENTERS, THERE ARE NINE OTHER INSTITUTES AND CENTERS AROUND NIH THAT HELP CO-FUND AND RUN THE NETWORK. AND JUST THE CONSORTIA CRITERIA BRIEFLY IS THAT A P.I. WOULD PROPOSE TO US A THERAPEUTIC GROUPING WITH AT LEAST THREE OR MORE RARE DISEASES INCLUDED IN IT. ACTUALLY MOST HAVE MORE DISEASES. THEY HAVE TO BE MULTI-CENTER. THEY MUST HAVE AT LEAST ONE PATIENT ADVOCACY GROUP, OR PAG, ASSOCIATED WITH THEM, THEY HAVE TO DO AT LEAST TWO STUDIES, ONE A LONGITUDINAL OBSERVATIONAL STUDY SUCH AS NATURAL HISTORY STUDY OR REGISTRY. AND THEY ALSO NEED TO DO PILOT STUDIES, AND TRAINING, FOR THE NEXT GENERATION OF RESEARCHERS. AND THE NETWORK IS HELD TOGETHER BY A DATA MANAGEMENT AND COORDINATING CENTER, DMCC. SO THIS IS JUST A SCHEMATIC OF THE RDCRN 3, AND IT'S HARD TO SEE, YOU MAY SEE IT BETTER IN YOUR PACKETS, BUT IT INCLUDES VERY DIVERSE GROUPINGS OF DISEASES AND THEY ARE GROUPED AROUND DIFFERENT THEMES. FOR EXAMPLE, AN ORGAN, HERE'S A RARE LUNG DISEASE OVER HERE, OR AN ORGANELLE SUCH AS LYSOSOMAL STORAGE DISORDERS OR MUTATIONS, BUT AS LONG AS IT'S A UNIFIED CONCEPT THAT MAKES SENSE, THE WHOLE IDEA HERE IS THAT THE DISEASES WILL LEARN FROM EACH OTHER WITHIN A CONSORTIUM, ALSO ACROSS THE NETWORK. ALSO INCLUDED IN THIS AS I MENTIONED THEY HAD TO BE AFFILIATED WITH AT LEAST ONE PATIENT ADVOCACY GROUP BUT THE REALITY IS MOST ARE AFFILIATED WITH MORE. WE CURRENTLY HAVE ABOUT 140 PAGs AFFILIATED WITH THE NETWORK, AND THEY FOCUS ON COMMUNICATION INTERNALLY, EXTERNALLY, EDUCATION IN THE PATIENT COMMUNITY, ALSO VERY IMPORTANTLY PATIENTS HAVE SPECIAL KNOWLEDGE OF THEIR DISEASE AND THEY NEED TO BE INVOLVED IN THE RESEARCH AGENDA WITHIN EACH CONSORTIUM. SO, WE HAVE A YEARLY IN-PERSON CPAG MEETING, QUARTERLY EDUCATIONAL MEETINGS THAT THE PATIENTS DECIDE WHAT THEY'D LIKE TO LEARN ABOUT. HERE'S A FEW HIGHLIGHTS FROM THE FIRST THREE AWARDEE COHORTS FOR THE RDCRN. YOU MORE THAN 200 PROTOCOLS, 2,000 PUBLICATIONS, THIS IS REALLY -- THAT'S FOR RARE DISEASES A REALLY HUGE NUMBER OF PATIENTS AND VERY SUCCESSFUL IN FURTHERING RARE DISEASE RESEARCH. AND THIS IS JUST ANOTHER WAY OF LOOKING AT THE NETWORK. THE RED STARS MEAN THEY ARE CO-LOCATED AT A CTSA HUB, BLUE BLOB IS A CTSA AFFILIATE, MOST OF THE RDCRN CONSORTIA ARE AT A CTSA SITE. I'M GOING TO GIVE YOU ONE EXAMPLE OF HOW THIS FORMAT HELPS ENABLE CUTTING EDGE TRIALS. THIS IS A PUBLICATION, NEW ENGLAND JOURNAL EARLIER THIS YEAR, AND THIS IS FOR THE PRIMARY IMMUNE DEFICIENCY THERAPEUTICS CONSORTIUM. THIS TRIAL WAS NOT FUNDED BY THE RDCRN, THE INFRASTRUCTURE OF THE RDCRN WAS USED TO HELP EFFICIENCY AND IDENTIFYING PATIENTS AND INVESTIGATORS WITH SKILLS FOR SEVERE COMBINED IMMUNE DEFICIENCY, SO IT FACILITATED LENTIVIRAL THERAPY, GENE THERAPY, FOR THIS DISORDER, AND THERE ARE QUITE A NUMBER OF OTHER EXAMPLES OF CUTTING-EDGE RESEARCH IN RARE DISEASES THROUGH THIS MODEL. A BRIEF WORD ABOUT RDCRN 4, WHICH WE'RE IN THE PROCESS OF STANDING UP, THIS IS THE FOURTH CYCLE OF THE NETWORK. AND SIMILAR PURPOSE, BUT WHAT WE'RE EMPHASIZING THIS TIME IS HIGHLY COLLABORATIVE MULTI-SITE NATURE OF THE NETWORK, AND ESPECIALLY CLINICAL TRIAL READINESS FOR UNMET MEDICAL NEEDS. SO QUESTION WE'RE ASKING, IF YOU'RE NOT IN THE CLINIC, WHY NOT, WHAT CAN WE DO TO HELP? AND SOME NEW FEATURES LIKE ALL OTHER NIH REQUIREMENTS A SINGLE IRB IS REQUIRED. THERE'S EXTERNAL ADVISORY COMMITTEE, AND WE'RE REALLY EMPHASIZING DATA SHARING. DATA SHARING, DATA STANDARDS, BEST PRACTICES ACROSS THE NETWORK. SO AS PART OF THAT, WITH THE NEW AWARD TO THE DMCC, WE'VE MIGRATED THE DATA CENTER TO THE NCATS HOSTED CLOUD COMPUTING SERVICES, SO TRYING TO GET AWAY FROM LOCAL CENTERS, AND MANY THANKS GOES TO THE NCATS CHIEF INFORMATICS OFFICER, SAM MICHAEL, AND HIS TEAM, WHO HAVE JUST BEEN TREMENDOUSLY HELPFUL IN GETTING THIS INFORMATICS COLLABORATIVE ACROSS THE NETWORK AND, AGAIN, WITH THE EFFORTS TO TRY TO FACILITATE DATA SHARING. AND THIS IS JUST A SCHEMATIC OF THE RDCRN4 AWARDEE COHORT, AND WE HAVE ALMOST ALL OF THE LETTERS OUT, THIS LAST FIVE THERE, BUT THE WHITE HONEYCOMB SHAPES ARE EXISTING CONSORTIA AND THE YELLOW ONES ARE NEW CONSORTIA. SO THIS IS TYPICAL OF EACH ITERATION, IS YOU GET OLD AND NEW TOGETHER, SO THAT THEY CAN LEARN FROM EACH OTHER. THE FUNDING FOR THE NETWORK FOR THE UPCOMING YEAR IS ABOUT $1.2 MILLION PER YEAR PER CONSORTIUM. NCATS PUTS IN $16.5 MILLION, AND IN TOTAL WITH THE OTHER ICs IT COMES TO $36.6 MILLION A YEAR. SO, THE AVERAGE AWARD FOR AN R01 IS ABOUT $500,000 TO $600,000 A YEAR FOR THE COST OF TWO R01s WE'RE GETTING A LOT FOR THE INVESTMENT. OKAY. I'M JUST GOING TO SWITCH GEARS AND TALK ABOUT GARD, THE RARE DISEASE INFORMATION CENTER, A COLLECTION OF THREE PROGRAMS, GARD TOOL KIT AND RADAR. SO GARD IS THE OLDEST ONE, IT GOES BACK TO 2002, AND IT IS ALSO A MANDATE, CONGRESSIONAL MANDATE AND IT STARTED ACTUALLY INITIALLY AS A WRITE-IN CALL-IN INFORMATION CENTER. SO, COMMON CUSTOMER, FOR EXAMPLE, WOULD BE A PARENT, THEIR CHILD HAS JUST GOTTEN DIAGNOSED WITH A DISEASE THEY HAVE NEVER HARD OF BEFORE AND THEY ARE LOOKING AROUND FOR INFORMATION. THEN IN 2008, THE WEBSITE WAS LAUNCHED, AND WE CURRENTLY HAVE 6500 RARE DISEASE PATIENTS. THIS IS ONE OF THE MOST COMPREHENSIVE RARE DISEASE SITES THAT'S OUT THERE, AND WHERE WE'RE DIFFERENT, THIS IS PLAIN LANGUAGE FOCUSED TOWARDS THE COMMUNITY. WE CONTINUE TOP OFFER THE INDIVIDUAL SERVICE AND TWO NEW PROGRAMS. PROGRAM LEADS ARE ERIC SID AND JIM DICKENS, BOTH SITTING OVER THERE. IF YOU CAME TO GARD, THIS IS WHAT IT WOULD LOOK LIKE. YOU CAN TYPE IN DISEASE OF INTEREST IF YOU WANT TO SEARCH, THERE'S ADDITIONAL SOURCES OF INFORMATION, OR CALL FOR AN INDIVIDUAL INQUIRY AT THE TOP. HARDLY ANYONE EVER COMES TO -- THANK YOU. HARDLY ANYBODY EVER COMES TO THE LANDING PAGE USUALLY. WHAT THEY WILL DO IS IT GOOGLE A DISEASE AND THEY WILL GO STRAIGHT TO A PAGE. SO THIS IS EXAMPLE, AND ALL THE PAGES LOOK LIKE THIS, THE SUMMARY INFORMATION AT THE TOP, AND THEN VARIOUS CATEGORIES OF INFORMATION INCLUDING THINGS LIKE FINDING A SPECIALIST, FINDING A RESEARCH TRIAL, IS THERE A PATIENT ORGANIZATION. SO WHAT IS UNIQUE ABOUT GARD WE EMPHASIZE PLAIN LANGUAGE, WE WANT TO BE ACCESSIBLE TO THE PUBLIC. SO I'M JUST DOING A CONTRAST HERE BETWEEN GARD AT THE TOP AND ONLINE MENDELIAN, SHARED BY MANY TIMES, JOINT HYPERMOBILITY, BRUISES EASILY, AND EQUIVALENT IS FEATURES OF SKIN HYPER ACCESSIBLE NOT VERY UNDERSTANDABLE -- HYPEREXTENSTIONABILITY. THE WEBSITE WAS LAUNCHED, 2,000 TO 4400 INQUIRIES A YEAR, WEBSITE BUILT OUT OF WHAT WAS BEING ASKED. IF SOMEBODY ASKED ABOUT A PARTICULAR DISEASE, SOMETHING WAS PUT UP ON THE WEBSITE, THERE WAS NO SYSTEMATIC APPROACH TO THIS. AND THEN IN 2012, WHEN NCATS WAS ESTABLISHED, THERE WAS A WEB SIDE SEARCH ENGINE OPTIMIZATION THAT INCREASED NUMBER OF INQUIRIES UP TO 1 TO 3 MILLION USERS A YEAR, DATA SHARING WITH OTHER NIH CENTERS, ALSO WITH GROUPS ON THE OUTSIDE. AND THEN MORE RECENTLY LAST YEAR WE HAD ABOUT 15.3 MILLION VISITORS TO THE SITE AND OVER 11,000 INQUIRIES SO THAT THE NEED FOR INFORMATION IS INCREASING, AND IT'S INCREASING EVERY YEAR. PUT ANOTHER WAY, THIS IS THE LAST SIX YEARS OR SO, THIS IS A NUMBER OF USERS, OVER HERE, AND IT'S REALLY INCREASING RATHER DRAMATICALLY, AND THE NUMBER OF INQUIRIES, THIS IS THE LAST FEW YEARS, RUNNING THE SAME AS LAST YEAR, BUT INITIALLY ESTIMATED 500 INQUIRIES A MONTH, AND WE'RE GETTING ABOUT TWICE THAT MANY. SO, THIS RAISES A NUMBER OF PROBLEMS. THE NUMBER OF DISEASES IN INCREASING 200, 250 A YEAR, THE VOLUME KEEPS INCREASING. HOW DO YOU KEEP UP WITH 6500 RARE DISEASE PAGES? AND THE WEBSITE IS OLD. AND WE'RE IN THE PROCESS OF UPDATING THAT SO WE'RE RIGHT IN THE MIDDLE OF A MAIN GARD RENOVATION. AND ALSO JUST TO PUT THE GARD TRAFFIC IN PERSPECTIVE THESE ARE THE NIH PAGES, AND GARD IS SOMEWHERE AROUND TOP TEN OF MOST TRAFFICKED WEBSITES IN NIH, THIS IS ALL OF HHS, GARD IS IN THE TOP 20, NOT ALL PAGES ARE TRACKED BUT I THINK AGAIN THIS GOES TO THE THIRST FOR RARE DISEASE INFORMATION OUT THERE, PEOPLE LOOKING FOR TRUSTED SOURCES FOR GOOD INFORMATION. WHAT ARE SOME THINGS WE'RE WORKING ON NOW? WE'RE TRYING TO STAY CURRENT, RELEVANT. SO WE ALSO MOVED TO THE NCATS CLOUD. THAT WAS A BIG MIGRATION AND EXPENSIVE BUT WILL GIVE US UNLIMITED CAPACITY AND LOWER COSTS IN THE LONG RUN. WHAT WE'RE TRYING TO DO RIGHT NOW IS ADDRESS THIS BACKLOG OF DISEASE INFORMATION, AND& ESPECIALLY HOW DO WE MODEL THIS SO WE CAN KEEP UP TO DATE WITH IT AND USE THINGS LIKE MACHINE INTELLIGENCE TO TRY TO PORT IN INFORMATION RATHER THAN RELYING SOLELY ON HUMAN CAPITAL. AND TO DO THIS, YOU HAVE TO BUILD OUT THE BACK END. THAT'S WHAT'S TAKING SO MUCH TIME. RESTRUCTURING THE DATABASE, REOING DATA MODEL AND PULLING IN MORE EFFICIENT WAYS OF ASSESSING OUR INFORMATION BUT ALSO WHY ARE PEOPLE COMING TO GARD. SO THIS ALL FEEDS INTO OUR FUTURE VISION, WHICH WE'RE CALLING DEEP ZEBRA. SO THIS REALLY FOCUSES ON HOW CAN WE USE INFORMATICS TOOLS TO INCREASE THE USE OF THE INFORMATION THAT IS THERE? SO WE'RE INVESTIGATING THINGS LIKE A CHAT BOX FOR CUSTOMER SERVICE, BUT ALSO THINGS TO INCREASE ACCURACY, BUT ALSO KEEP UP TO DATE ON THE CONTENT AND CAN WE BE INTEROPERABLE WITH OTHER SOURCE, INSIGHT, DRUGGABLE GENOME, GARD HAS A LOT OF PHENOTYPIC INFORMATION SO ARE THERE WAYS TO PUT THESE TOGETHER AND COULD YOU DEVELOP, FOR EXAMPLE, DECISION SUPPORT TOOLS OR TOOLS TO ANSWER RESEARCH QUESTIONS FOR RARE DISEASES. AND JUST A BRIEF WORD HERE ABOUT THE TOOL KIT AND RADAR, SO TOOL KIT WAS LAUNCHED TWO YEARS AGO, THIS WAS AT THE REQUEST OF THE PATIENT COMMUNITY. AND WE COLLECTED INFORMATION THAT WAS ALL OVER THE PLACE, DEVELOPED BY OTHER PEOPLE, PATIENT GROUPS, THAT WOULD HELP PATIENT GROUPS FURTHER RESEARCH AGENDA SO WE TALKED ABOUT THAT PREVIOUSLY BUT THAT WAS LAUNCHED TWO YEARS AGO. AND THEN MORE RECENTLY RADAR, RARE DISEASE REGISTRY PROGRAM, I'LL SAY A WORD ABOUT THAT, INITIALLY LAUNCHED IN 2017 BUT IT WAS RELAUNCHED A FEW MONTHS AGO, WITH IMPROVED CONTENT AND USABILITY. WE'RE TRYING TO BE SOURCE OF INFORMATION TO PATIENT GROUPS ON HOW WE CAN BUILD THEIR OWN REGISTRIES. SO IT'S LIKE AN E-BOOK, STEP BY STEP, USER FRIENDLY FOR PATIENT GROUPS. SO, HERE IS THE SET UP YOUR REGISTRY TAB. IF YOU GO TO THE CREATIVE REGISTRY PLAN, IT WILL GIVE YOU STEP ONE, STEP TWO. THERE ARE TEMPLATES IN THERE THAT ARE DOWNLOADABLE TOOLS, THIS LAUNCHED AROUND RARE DISEASE DAY EARLIER THIS YEAR. WE'VE ACTUALLY HAD TREMENDOUS FEEDBACK FROM THE PATIENT COMMUNITY ON THIS. IT'S VERY EASY TO USE. PRETTY MUCH ANYBODY CAN PICK IT UP, IT'S TRYING TO WALK PEOPLE THROUGH THE PROCESS. REGISTRIES ARE EXTREME UTILITY FOR RARE DISEASES, OFTEN A WAY OF RESEARCH PROGRAMS GET STARTED. SO WE'RE TRYING TO HELP AS MANY PATIENT GROUPS AND AS MANY DISEASES GET STARTED AS WE CAN. OKAY. SO I'M GOING TO SWITCH GEARS NOW TO THE PLATFORM VECTOR GENE THERAPY PROJECT, PAVING THE WAY FOR GENE THERAPY, AND THIS IS ACTUALLY NOT AN ORDR PROGRAM. IT'S A COLLABORATION BETWEEN ORDR, THERAPEUTICS DEVELOPMENT BRANCH, AND NCATS OFFICE OF STRATEGIC ALLIANCE AND HUMAN GENOME AND NINDS. SO, WHAT THIS IS IS A CURES ACCELERATION NETWORK PROJECT, AND WE'RE GETTING BETWEEN $4 TO $6 MILLION A YEAR FUNDING FOR THIS. THE PLATFORM, LANGUAG BORROWED FROM THE CANCER RESEARCH WORLD, A DURABLE INFRASTRUCTURE THAT WILL SUPPORT TESTING OF MULTIPLE THERAPIES, AND MULTIPLE DISEASES. AND THE NEEDS FOR THIS ARE OVER HERE, AND DON MULLEN, TRENT, WHEN YOU HIGHLIGHT PEOPLE, THERE ARE A LOT OF PEOPLE THAT NEED TO BE MENTIONED SO WE HAVE MANY COLLABORATORS AND MANY PEOPLE WORKING ON THIS WITHIN NCATS AND WITHOUT, SO IT'S A TRUE COLLABORATION. SO, WHAT IS THE PROBLEM WE'RE TRYING TO SOLVE HERE? SO THE CURRENT APPROACH TO GENE THERAPIES IS ONE DISEASE AT A TIME, AS WE MENTIONED, THIS IS TOO SLOW. AND IT'S OFTEN INEFFICIENT. YOU'RE DUPLICATING EFFORT FOR THE SAME VECTOR, SO OUR HYPOTHESIS, AS MANY DISEASES AS CAN BE TREATED BY GENE THERAPY, RIGHT NOW MANY ARE BEING TREATED WITH THE -- OR BEING INVESTIGATED WITH THE ADENOASSOCIATED VIRUS THAT WILL DELIVER THERAPEUTIC GENE TO THE TISSUES THEMSELVES. THUS FAR WE'VE GOT EXCELLENT SAFETY RECORDS IN HUMANS, BUT ALSO IN ANIMALS, THERE'S RECENTLY APPROVED PRODUCTS, AND MANY CLINICAL SUCCESS STORIES, SO COULD A PLATFORM SUPPORT MULTIPLE DISEASES AT THE SAME TIME RATHER THAN DOING THIS, THIS ONE-OFF THAT HAS BEEN GOING ON. SO THIS IS JUST A SCHEMATIC OF I GUESS THE CONCEPT, SO YOU HAVE OVER HERE, HERE'S A VERY SIMPLISTIC DIAGRAM OF AN AAV CAPSID WITH VITAL DNA. THE DNA IS PULLED OUT. NOW YOU HAVE AN EMPTY CAPSID THAT YOU CAN THEN FILL WITH THE SEQUENCE OF INTEREST. HERE A RED OR BLUE ONE. YOU MADE YOUR NEW PRODUCT. SO THE VIRAL VECTOR IS LIKE THE SUITCASE. TAKE YOUR SUITCASE, EMPTY IT OUT, YOU CAN PUT CLOTHES IN IT, PUT BUNNY RABBITS IN IT, CLOSE THE SUITCASE, IT LOOKS THE SAME. SO THE QUESTION IS DOES THE VIRAL CAPSULE, DOES IT LOOK THE SAME REGARDLESS OF THE PAYLOAD, SO THAT'S THE GENERAL PRINCIPLE. SO, WHAT OUR PILOT PROJECT IS, OR WHAT WE'RE TRYING TO DO, IS TAKE DISEASES, SAME VIRAL VECTOR, SAME ROUTE OF ADMINISTRATION, IV, SAME PRODUCT PURIFICATION METHOD, THE PROCESS IS THE PRODUCT BUT DIFFERENT THERAPEUTIC GENE. AND THEN MAKE ALL THE DATA COMMUNICATIONS, EVERYTHING PUBLIC, BECAUSE IF THIS WORKS, AND WE HOPE IT DOES, WE'RE HOPING OTHER PEOPLE WOULD BE ABLE TO TAKE THE INFORMATION GENERATED HERE AND BE ABLE TO USE IT AND WE'LL GET MANY EFFICIENCIES OUT OF THIS. SO THIS IS EARLY STAGE, STAY TUNED. WE'RE JUST GETTING STARTED. THIS IS ANOTHER WAY OF LOOKING AT IT. PROCESS, PURIFICATION METHOD, YOU CAN MAKE MANY GENES WITHIN THE SAME VIRAL VECTOR AND CAN THAT LEAD TO EFFICIENCIES IN THE CHARACTERIZATION, DISTRIBUTION, TOXICOLOGY, AND THEN WHEN WE TEST THESE THINGS, BORROWING AGAIN FROM CANCER THERAPIES, CAN WE RUN THIS IN AN UMBRELLA TRIAL, AND UMBRELLA IS DEFINED AT MORE THAN ONE DIFFERENT TREATMENT WITHIN ONE TRIAL. SO,S PEOPLE ARE ASSIGNED TO THAT ARM DEPENDING ON WHAT THE UNDERLYING MOLECULAR MAKEUP IS OF THE DISEASE. SO, YOU HAVE A RELATED DISEASES, AT LEAST PHENOTYPICALLY SIMILAR. WE TEST PEOPLE, MUTATIONS ARE DIFFERENT, ASSIGNED TO THE GENE BASED MOLECULAR UNDERPINNINGS BUT THE DISEASES LIKE SIMILAR ENOUGH THEY CAN BE TESTED IN THE SAME PROTOCOL, GET THE SAME OUTCOME MEASURES, SAME INVESTIGATORS, SAME SITES. SO THERE'S A LOT OF EFFICIENCIES THAT COULD BE HAD. AND THEN ANOTHER GENE THERAPY INITIATIVE THAT P.J. TALKED ABOUT LAST TIME WE WERE HERE IS THE MANUFACTURING INITIATIVE, WE'RE IN THE 1X NOW, BUT MANUFACTURING AS WE MENTIONED BEFORE IS A BOTTLENECK RIGHT NOW. CAN WE AIMPROVE THAT MANUFACTURING EFFICIENCY TEN-FOLD, 100-FOLD, SO THAT'S UNDER DEVELOPMENT. JUST BRIEFLY MENTION A COUPLE OTHER PROGRAMS, CONFERENCE GRANTS WE TALKED ABOUT CLINICAL TRIAL READINESS RARE DISEASES, AND THEN THE CLINICAL CENTER BENCH TO BEDSIDE PROGRAM WHICH WE PARTICIPATED IN, THAT'S EXACTLY WHAT IT SAYS HERE, TRYING TO MOVE THINGS FROM THE BENCH TO THE BEDSIDE, IT'S AN INTRAMURAL/EXTRAMURAL COLLABORATION WHICH WE'VE BEEN SUPPORTING FOR MANY YEARS. I'LL JUST SAY A FEW WORDS ABOUT THE CLINICAL TRIAL READINESS GRANTS AND PROJECT WITH ALICE CHEN RIGHT THERE, AND THESE ARE R21s OR RO3s. R21s ARE INNOVATION GRANTS, AND RO3s ARE SMALL GRANTS. THIS WAS A NEW PROGRAMMATIC ANNOUNCEMENT EARLIER THIS YEAR. THE PURPOSE HERE IS TO TRY TO SUPPORT PROJECTS THAT ADDRESS CRITICAL NEEDS IN CLINICAL TRIAL READINESS. FOR EXAMPLE, DEVELOPMENT TESTING VALIDATION OF A BIOMARKER OR CLINICAL OUTCOME MEASURE OR BETTER CHARACTERIZATION OF THE POPULATION THAT YOU COULD SELECT FOR A CLINICAL TRIAL. SO IT'S HARD TO FIND FUNDING FOR RESEARCH SUCH AS THIS, AND WE'VE ACTUALLY HAD A LOT OF INTEREST IN THE PROGRAM. THE NEXT RECEIPT DATE IS OCTOBER 24, THERE'S TWO RECEIPT DATES A YEAR. AND FIRST CYCLE OF AWARDS WENT OUT, WE GOT A BROAD VARIETY OF DISEASES, METABOLIC, NEUROLOGIC, AUTOIMMUNE AND RENAL. WORDS ABOUT OUR ENGAGEMENT PROGRAM, ALICE WILL BE TALKING ABOUT RARE DISEASES, BUT JUST A WORD HERE ABOUT RARE DISEASE DAY AT NIH. SO, AGAIN, ALICE IS THE LEAD ON THIS. RARE DISEASE DAY AT NIH IS AN INTERNATIONAL EVENT. IT FIRST BEGAN IN 2008, IN EUROPE, AND CAME TO THE U.S. THE FOLLOWING YEAR. THEN BECAME AN ANNUAL EVENT AT NIH, BEGINNING IN 2011. SO THIS IS AN NCATS CLINICAL CENTER COLLABORATION, AND THE PURPOSE IS TO RARE AWARENESS ABOUT RARE DISEASE, PEOPLE THEY AFFECT AND SHOWCASE NIH RESEARCH IN THIS DIRECTION. AND THERE'S USUALLY A TWITTER CHAT THAT PRECEDES RARE DISEASE DAY, TWO WEEKS AHEAD OF TIME, WHICH IS ALWAYS VERY POPULAR. VERY BRIEFLY, THERE IS A LOT OF COMMUNITY INTEREST IN THIS, AND THIS GRAPHIC HERE IN THE LINE SHOWS INCREASING ATTENDANCE. LAST YEAR WE HAD 700 ATTENDEES, GOT TOO BIG AND HAD TO MOVE TO NATCHER, AND FEATURES PANEL DISCUSSIONS, POSTERS, EXHIBITS, DEMOS, AND EVERYTHING JUST INCREASES YEAR OVER YEAR OVER YEAR. SO, AGAIN, I THINK IT GOES TO THE INTEREST IN RARE DISEASES AND ALSO THIS THIRST FOR RARE DISEASE KNOWLEDGE AND PEOPLE WHO ATTEND IT'S PREDOMINANTLY PATIENTS AND ADVOCATES, RESEARCHERS AND A VARIETY OF PEOPLE. THIS TURNED INTO A HUGE EVENT AND THE FEEDBACK IS JUST EXTREMELY POSITIVE. A COUPLE OTHER THINGS WE'RE WORKING ON, SO THIS IS A NEW PROJECT, BURDEN OF RARE DISEASES, WE'RE TRYING TO GET A BETTER HANDLE ON WHAT THE HEALTHCARE SYSTEM UTILIZATION FOR RARE DISEASES, WE'RE PRETTY SURE IT'S QUITE HIGH BUT NEVER REALLY BEEN QUANTIFIED, NOT HERE IN THE UNITED STATES. SO WE WOULD LIKE TO UNDERSTAND THAT BETTER. AND RELATED TO THIS ARE THINGS LIKE MISDIAGNOSIS, THAT'S A PROBLEM. HOW MUCH IS THIS GOING ON FOR PATIENTS? HOW MUCH OF A BURDEN IS THIS TO PATIENTS? CAN WE QUANTIFY OBJECTIVELY SOME OF THE THINGS THAT ARE GOING ON? SO THIS IS ALSO VERY EARLY DAYS. AND THEY ARE SITTING OVER THERE GETTING THIS GOING. I WANT TO BRIEFLY MENTION THAT ARE STAFF ARE ON A LOT OF COMMITTEES, EXTERNAL AND INTERNAL TO NIH. AND INCLUDING THE INTERNATIONAL RARE DISEASES RESEARCH CONSORTIUM, WE HAVE MULTIPLE NCATS MEMBERS ON THAT AND AROUND NIH AND EXTERNALLY THESE ARE FOR THE MOST PART VOLUNTEER ACTIVITIES IN ADDITION TO THE WORK WE'RE DOING TO HELP THE EXTERNAL COMMITTEE MOVE SOME RESEARCH FORWARD. TO SUMMARIZE BRIEFLY, SMALL STAFF, SMALL BUT MIGHTY, TINY BUDGET, A VARIETY OF PROGRAMS WE'RE TRYING TO ADDRESS A NUMBER OF MANY NEEDS OF THE RARE DISEASE RESEARCH COMMUNITY. I PUT SOME QUESTIONS FOR COUNCIL. BUT WE WOULD LIKE TO HEAR YOUR THOUGHTS. PLEASE DISCUSS PROGRAMMATIC PRIORITIES, DO YOU FEEL WE'RE ON THE RIGHT TRACK, CRITICAL AREAS NOT BEING ADDRESSED, THINGS WE SHOULD DO MORE OR LESS OF, OR NEW IDEAS >> ALL RIGHT. THANK YOU, ANNE. I'M GOING TO NOT EMCEE THIS. I'LL ASK ANNE TO EMCEE IT. SO WE'RE REALLY INTERESTED IN THESE. YOU HEARD THE CHALLENGES. OPPORTUNITIES ARE ALMOST INFINITE. THE NUMBERS ARE REALLY QUITE ASTOUNDING, AS ANNE SHOWED YOU. AND YET THE BUDGET IS QUITE MODEST. AND SO ARE WE USING IT IN THE BEST WAY, ARE THERE THINGS WE'RE NOT DOING, ARE THERE THINGS WE COULD STOP DOING? AND SO I'LL LET ANNE KICK THIS OFF. WE'LL BE TAKING NOTES SO PLEASE GIVE US YOUR BEST IDEAS. >> A GENERAL QUESTION. IN THE BEGINNING YOU WERE CLEAR ABOUT THE DEFINITION OF "RARE," 200,000 PEOPLE IN THE U.S. WHAT'S NOT CLEAR TO ME, WHAT THE DEFINITION OF A DISEASE IS. AND I WOULD IMAGINE THAT'S VERY IMPORTANT FOR MANY IMPLICATIONS FOR HOW YOU ORGANIZE THE PROGRAM. IS IT A GENE DEFECT? I CAN IMAGINE VERY COMMON DISEASES PULLING OUT VARIABLE PHENOTYPES, WITH SUBPOPULATIONS LESS THAN 00,000 EVEN THOUGH WE CONSIDER THEM NOT RARE DISEASES, SO IS THAT A RARE DISEASE? OR IF YOU TAKE A DISEASE LIKE CYSTIC FIBROSIS, 2% HAVE THIS MUTATION, 3% HAVE THAT MUTATION, I'M WONDERING HOW YOU'RE THINKING ABOUT THIS, HOW YOU AND YOUR COLLEAGUES ARE THINKING ABOUT IT? >> THAT'S A GREAT QUESTION. THAT'S SOMETHING I HAVE TO TELL YOU WE'RE STRUGGLING WITH. WHAT IS A DISEASE EXISTENTIAL QUESTION, NOBODY HAS THE ANSWER TO IT. THERE'S DISAGREEMENT. THE DEFINITION IS GENE BASED, SO HUMAN PHENOTYPE ONTOLOGY IS ALMOST ENTIRELY PHENOTYPICALLY BASED, THEN THERE'S GRADATIONS IN BETWEEN. SO, THERE'S NO HARD LINE. IT DOES GET VERY GRAY. AND SOME OF THE THINGS THAT YOU MENTIONED, TAKING COMMON DISEASES AND SUBDIVIDING THEM BY THEIR GENETIC UNDERPINNINGS, THAT'S ACTUALLY GOING ON RIGHT NOW IN CANCER, REALLY LEADING THE WAY, CERTAIN TIMES OF LUNG CANCER, FOR EXAMPLE, CAN ARE CONSIDERED RARE BECAUSE YOU'RE SPLITTING GENETIC UNDERPINNINGS. >> FOR TRANSLATION, IT HAS BIG IMPACT. >> RIGHT. >> BECAUSE INCENTIVE TO WORK ON RARE DISEASES WE KNOW IS VERY GREAT BECAUSE OF THE KIND OF PRIVILEGE OF THAT SPACE, AND SO SOME DISEASES WOULD BE IN OR OUT DEPENDING ON HOW YOU VIEW THEM. >> RIGHT, EXACTLY. IT'S AN EVOLVING AREA OF DISCUSSION RIGHT NOW. >> I HAVE A LIST. >> YES, PLEASE, GO AHEAD. >> SO, ONE OF THE THINGS I PREACH IS WHAT DR. ALSTON PREACH, WE'RE NOT DOING THIS DO THIS ONE AT A TIME. THE DISEASE OF MY DAUGHTER IS NEURODEVELOPMENTAL DISSEMINATION ORDER, AUTISM AND EPILEPSY, OUR ORGANIZATION AND TWO DOZEN OTHERS THAT LOOK ALIKE WITHOUT A GENETIC TEST COLLABORATE BY PHONE, LOOK FOR BIO, MAKERS, RESEARCH, PLAY WELL IN THE SANDBOX BUT DON'T SEE A LOT OF FUNDING OPPORTUNITIES TO DO THAT. THERE'S A LOT OF THINGS WE CAN DO, WE TALKED ABOUT AN ECHO PROJECT WHERE EXPERTS CAN BE BROUGHT IN ON VIDEO PANELS AND CONSULT. G.I. ISSUESES FAMILIES HAVE IN PHALEN MCDERMID ARE NO DIFFERENCE THAN FRAGILE FRAGILE X. THERE'S A LOT OF THINGS, NEURODEGENERATIVE OR AUTOIMMUNE, THEY CAN WORK TOGETHER. BUT I THINK IF THERE WAS SOME FUNDING MECHANISMS TO GET THEM TO WORK TOGETHER, THAT WOULD BE GREAT. ALSO, PREACHING TO THE CHOIR, THE GLOBAL UNIQUE IDENTIFIER ISSUE IS AN ISSUE FOR RARE DISEASES. AND YOU GET ENTHUSIASTIC FAMILY THAT WANTS TO BE IN RESEARCH AND THEY JOINT EVERY REGISTRY AND EVERY STUDY. THAT DATA GETS DE-IDENTIFIED, SOME GREAT RESEARCHER COMES ALONG AND GETS DATA FROM SIX DIFFERENT DATABASES, AND PUBLISHES THAT, SIX OUT OF SEVEN TEAM WITH THIS DISEASE HAVE X. IT'S THE SAME KID SIX TIMES. THAT'S A PROBLEM. AND FRANKLY, THERE'S A LOT OF US IN THE RARE DISEASE COMMUNITY THAT WOULDN'T MIND IF WE WERE JUST IDENTIFIED. BUT THAT'S A WHOLE OTHER CONFERENCE. ALSO HAS BEEN POINTED OUT, RARE IS NOT RARE. IT'S RARELY DIAGNOSED. AND EVEN IF EVERYBODY WITH AUTISM AND EPILEPSY WERE GENETICALLY TESTED OUR DISEASE WOULD GO FROM 2,000 IN THE WORLD TO 10,000 IN THE UNITED STATES, RARE BUT LESS RARE WHICH MAKES CLINICAL TRIALS A HECK OF A LOT EASIER. THAT'S A GENETIC TESTING PROBLEM. AND THAT'S BECAUSE PEOPLE AREN'T -- THE PRICES COME DOWN, THE TECHNOLOGY HAS GONE UP, BUT THE GENETIC TESTS AREN'T BEING ORDERED. AND THAT'S SPECIFICALLY A HUGE PROBLEM IN THE UNDERSERVED MINORITY AREAS. I MEAN, PHELAN MCDERMID IS NOT WHITE SYNDROME BUT LOOKS LIKE IT IF YOU LOOK AT THE REGISTRY AND MEMBERSHIP. AND I DIDN'T REALIZE THERE WAS AN INSTITUTE OR CENTER THAT WAS AROUND -- ONE OF THE GROUPS, CHRIS, THAT YOU HIGHLIGHTED TODAY THAT'S GOING TO CONGRESS, THE MINORITY -- OR -- IF THEY COULD WORK WITH NCATS AND GENETIC INSTITUTE ON FUNDING SOME MINORITY GENETIC TESTING. WE HAD PCORI MONEY, I HAD TO SAY TO PCORI WE'RE NOT GOING TO MEET YOUR MILESTONE THAT WE'RE GOING TO INCREASE, YOU KNOW, THE DIVERSITY BECAUSE IT'S A SOCIOECONOMIC PROBLEM THAT I CAN'T SOLVE. BUT IF WE GET SOME FUNDING BEHIND IT MAYBE WE COULD GET SOME OF THESE UNDERSERVED POPULATIONS GENETICALLY TESTED. I'M ALMOST FINISHED. DRUG PRICING IS GOING TO BE A HUGE PROBLEM. IT IS A HUGE PROBLEM. LOOK AT SMA, FOR THIS COMMUNITY. AND WE'VE HAD ALL THIS LEGISLATION TO GET PEOPLE TO COME AND WORK IN IT THE RARE DISEASE POPULATION, THE ORPHAN DRUG ACT ANDED OTHER ALPHABET ACTINGS, PDUFA AND THE OTHERS, BUT IF THESE TREATMENTS COME UP AND NOBODY CAN AFFORD THEM, THAT'S GOING TO BE A PROBLEM. SO I THINK SOME RARE DISEASES HAVE COME TOGETHER TO TRY AND FIGURE OUT WHAT STAKEHOLDERS DO WE HAVE TO WORK WITH, YOU KNOW, INDUSTRY MIGHT NOT NECESSARILY BE THE BAD GUY. IS IT THE OTHER STAKEHOLDERS THAT ARE INTERFERING WITH THE PRICING? AND THE REST OF MY LIST -- >> WITH THAT IN MIND, DO YOU HAVE RECOMMENDATIONS FOR US AT NCATS? PERHAPS WHERE WE SHOULD EXPAND OR SHIFT OUR FOCUS? >> YOU KIND OF HAVE A SMALL BUDGET. I THINK THERE'S WAYS TO LEVERAGE OTHER INSTITUTES AND CENTERS TO HELP FUND SOME OF THESE THINGS. I AM PARTICULARLY PREACHY ABOUT HAVING RARE DISEASES WORK TOGETHER ON THINGS. SO I THINK AT A MINIMUM, FUNDING COLLABORATIVE PROJECTS, WHERE WE CAN SHOW THE BENEFIT OF HAVING RARE DISEASES WORK TOGETHER, AND ALSO TO DR. ROSENBLAT'S POINT, AS TECHNOLOGY GETS BETTER WE'LL GET SLICE AND DICED, MPS I 23, SAN FELIPE, NOT JUST COMMON DISEASES, I MEAN, I REALLY THINK GENETIC TESTING IS AN ISSUE AND I DON'T THINK THAT NCATS SHOULD HAVE TO CARRY THE BURDEN ALONE, BUT I DO THINK IF YOU COULD FUND SOME COLLABORATIVE MANDATED COLLABORATIVE EFFORTS THAT WOULD BE GREAT. >> THANK YOU. JUST TO ENHANCE WHAT YOU SAID, ONE OF THE BIG ISSUES WE HAVE TO TACKLE AS A SOCIETY IS THE UNIQUE GLOBAL PATIENT IDENTIFIER. AND IT'S NOT JUST THE PROBLEM FOR RARE DISEASES ALONE. THAT'S WHY I BRING IT UP AGAIN. IF YOU DON'T DO IT, YOU THROW CHARLATANS AND PEOPLE WHO MISREPRESENT. WHAT WE NEED AS SOCIETY AND PERHAPS AS A GOVERNMENT IS A GOVERNANCE PLAN HOW TO PROTECT INDIVIDUALS AND ENTITIES FROM MISUSE AND ABUSE THEREOF. BUT NOT TO DISCONNECT. THIS IS NOT HOW WE MAKE PROGRESS. I'M CLEAR AND I HOPE YOU TAKE NOTE AND BRING THIS UP WHEREVER YOU CAN BECAUSE THIS IS AN ADVANCE THAT WE HAVE TO MAKE. >> SHOULD THAT BE AN INTERNATIONAL EFFORT? >> ABSOLUTELY. IT'S ALSO VERY IMPORTANT FOR THIS SOCIETY. YOU CANNOT MAKE PROGRESS IN DEALING WITH HEALTH AND WELLNESS IF YOU CANNOT CONNECT OUR PATIENTS AND INDIVIDUALS. AGAIN, IT'S A QUESTION OF GOVERNANCE AND PROTECTING INDIVIDUALS, HAVING THAT, LET'S SAY, POLICE. IT CANNOT BE UP TO THE INDIVIDUAL AS A SOCIETY. MODERN SOCIETY CANNOT LEAVE IT UP TO THE INDIVIDUAL TO PROTECT THEMSELF FROM IDENTITY FRAUD, FOR EXAMPLE, THAT GOES INTO THIS DIRECTION JUST TO MAKE CLEAR WHAT I'M TALKING ABOUT. THERE ARE SOME OTHER ISSUES I THINK OR OPPORTUNITIES THAT I THINK I FEEL THAT YOU SHOULD CONTINUE AND ENHANCE AND TO THE EXTENT I BELIEVE YOU HAVE IT RIGHT SO THERE ARE TWO KITS AND PLATFORMS THAT SHOULD INCLUDE CARE, DIAGNOSTIC, AS WELL AS THERAPY. AND SO PLEASE CONTINUE THAT DIRECTION, IN TERMS OF DATA AND EVIDENCE, REAL WORLD DATA AND REAL WORLD EVIDENCE, CONTROLLED REGISTRY NETWORKS, OR REGISTRIES, PLATFORM TRIALS, AND THE OPPORTUNITY TO HAVE ACCESS TO THE DATA. SO HEALTH DATA LIBERATION, THE WHOLE SCHPIEL, THIS IS WHERE THE WHOLE FIELD IS STRUGGLING WITH. IT BECOMES EMINENT IN RARE DISEASE, AND ACTIVISM OF PEOPLE IN RARE DISEASE IS ESSENTIAL TO MOVE SOME OF THIS FORWARD. DRUG PRICING OF COURSE IS A DIALOGUE WE HAVE IN MANY AREAS. BUT ALSO HERE. PLEASE MAKE THAT CONTRIBUTION AND LETS DISCUSS HOW WE LEAD THIS SOCIETY INTO DIFFERENT WAYS OF VALUING DRUG PRICING AND IMPACT WE CAN HAVE WITH IT. >> A LOT OF THINGS WERE EXCITING TO ME, BUT THE UMBRELLA TRIALS PART SPURRED ME. AND I THINK THAT RESEARCH CAN MAYBE ACT AS A CATALYST WITH FDA TO FIGURE OUT HOW TO DO THESE THINGS SO THAT WE JUST CAN'T THE WAY WE ALWAYS DID. RIGHT AT THIS MOMENT, IN A FEW WEEKS STARTING THE FIRST CLINICAL TRIAL, ASO, FIRST ONE IN HISTORY WITH A LITTLE GIRL, MOVED FROM CALIFORNIA TO BOSTON LAST WEEKEND, AND SO IT'S BEEN DEVELOPED FOR HER MUTATION. IT HAS 400 KIDS IN THE U.S., THAT MAKES IT I THINK RARE. ALMOST ALL HAVE DIFFERENT MUTATIONS. HOLY COW, NOW IT'S RARER. ONE OR TWO, MAYBE THREE OR FOUR WITH THE SAME MUTATION, SO WE SPENT A MILLION AND A HALF DOLLARS GETTING TO IND FOR ONE DRUG THAT TREATS ONE MUTATION, AND IF IT WORKS, IT'S NOT VERY PRACTICAL, BUT I DECIDED IF IT WORKS IT'S A PRETTY COOL THING TO HAVE IN YOUR BACK POCKET, YOU CAN RAISE MONEY AND HAVE CONFERENCES EVERY WEEK TO SCALE AND MAKE IT CHEAPER. ALONG THOSE LINES FIGURE OUT CAN WE POOL THEM, CAN WE SOMEHOW AFTER THE TENTH TIME WE DO IT SAFELY GET THE FDA TO REQUIRE LESS TOX IN RATS, BUT EVEN ON THE CLINICAL TRIALS SIDE ON THIS THING WHERE IT'S THE SAME READOUT, THE SAME BASELINE AND FOLLOW-UP THAT YOU DO, IS THERE A WAY WE CAN GET MORE EFFICIENT THAN -- THIS IS GOING TO BECOME MORE URGENT FOR EVERY SINGLE DISEASE. IN FACT, DOESN'T REALLY MATTER, IF THE OTHER DISEASES IS THIS OR NOT, BY DEFINITION OF DISEASE IT'S THE DESIGN OF THE TRIAL. YOU CAN IMAGINE A BUNCH OF RARE DISEASES THAT ARE NOT REALLY SIMILAR EXCEPT THAT TRIAL DESIGN IS PRETTY MUCH THE SAME, NEUROLOGICAL MOVEMENT DISORDER, YOU COULD PUT THEM TOGETHER. I DON'T KNOW WHAT THE EFFICIENCIES OR ECONOMIES OF SCALE ARE DOING THAT WAY BUT THE WAY YOU DO IT NOW, ALTHOUGH I'VE PLACED SOME BETS ON IT, IS WAY TOO EXPENSIVE AND NOT PRACTICAL, I THINK THAT'S AN AREA WHERE I CAN'T DO, A COMPANY CAN'T DO, WHAT NCATS COULD DO TALKING TO THE FDA ABOUT IT. >> I JUST WOULD LIKE TO ADD THAT AS PART OF THE THIS PLATFORM, DID GO MEET WITH FDA AND CENTER FOR BIOLOGICS, NOT CENTER FOR DRUGS WHICH I THINK YOU'RE PROBABLY DEALING WITH, BUT THEY ARE VERY SUPPORTIVE OF THIS CONCEPT. AND THEY ACTUALLY ARE WORKING TO BE ENGAGED AND TO HELP. SO THAT WAS VERY ENCOURAGING. >> SO GETTING BACK TO WHAT SHOULD WE DO MORE OR LESS OF, IF I BREAK IT DOWN INTO THREE DIFFERENT AREAS, SO ONE IS YOU HAVE TO IDENTIFY IT AND NAME IT. TWO, YOU HAVE TO DIAGNOSIS. THREE, YOU HAVE TO TREAT IT. I DON'T KNOW WHAT PART OF YOUR BUDGET GOES INTO EACH ONE OF THOSE, OR WHERE YOU THINK IT SHOULD GO, IN TERMS OF PLAYING TO YOUR EXPERTISE, SO 24 MILLION ISN'T A LOT OF MONEY IN THIS SPACE. STRATEGICKICALLY THINKING ABOUT NAMING THEM, INFORMATION ON THE DIAGNOSTIC PART, MANY PATIENTS WANDER IN THE WILDERNESS FOR YEARS, SOMETIMES A LIFETIME, AND NEVER ACTUALLY GET A DIAGNOSIS. IS THERE INNOVATION AROUND THAT THAT COULD BE DONE TO TRY TO BRING THEM IN? SO THAT'S HOW I WOULD ADDRESS SOME OF YOUR QUESTIONS OUT THERE. >> DO YOU WANT TO SAY WHAT WE'RE DOING IN THOSE AREAS? >> SURE. >> IT'S NASCENT. WE WERE THINKING ABOUT WHAT BRAD WAS SAYING, I LIKE TO NEEDLE ANNE BY SAYING SHE DOESN'T HAVE 7,000 DISEASES, IT'S 100,000 MUTATIONS ACROSS EVERY DISEASE, THAT'S HOW MANY RARE DISEASES THERE ARE ON A MOLECULAR LEVEL. HER PROBLEM GOT THREE ORDERS OF MAGNITUDE BIGGER, THEY ARE MUTATION DEPENDENT, THAT SHOWS YOU WE'VE GOT TO HAVE WAYS TO DO THIS THAT SCALE SO THOSE CONVERSATIONS OF WHAT WOULD YOU HAVE TO DO TO MAKE THIS A PLATFORM MAKE IT A -- HAVE THIS BE A CLASS EFFECT, SO THIS KIND OF MUTATION, HOW MANY WOULD YOU HAVE TO DO, TO DO ALL THE TOX AND CMC AND MANUFACTURING AND ALL THAT STUFF, BEFORE THE FDA WOULD SAY, OKAY, IT'S ANOTHER SUITCASE THING, AS LONG AS YOU USE THIS OLIGO OF THIS LENGTH, THIS KIND OF MUTATION, WE'RE GOOD. IT'S NOT GOING TO SOLVE ALL THE DISEASES BUT IT WILL SOLVE A LOT. SO THAT'S THE KIND OF THING THAT WE'RE THINKING ABOUT. BUT DO YOU WANT TO TELL THE GROUP WHAT WE'RE THINKING ABOUT ABOUT THE DIAGNOSTIC THING? BECAUSE THAT'S A HUGE AREA. >> SURE. SO THIS IS PART OF THIS BURDEN OF DISEASE THAT I JUST BRIEFLY MENTIONED. SO, WE'RE TRYING TO SEE CAN WE LEVERAGE EXISTING DATABASES, SO FOR EXAMPLE INSURANCE DATA BASES, OR SOME HEALTHCARE SYSTEM DATABASE, AND CAN YOU LOOK FOR WITHIN DIAGNOSTIC CODES, PROCEDURES, DRUG USES, PATTERNS OF SOME KIND, CAN YOU IDENTIFY PATIENTS THAT PROBABLY HAVE A RARE DISEASE, WE DON'T NECESSARILY HAVE TO SAY WHAT THAT DISEASE IS BUT CAN YOU IDENTIFY THEM AND ESCALATE THEM FASTER AND THEN MOVE THEM TO COMBINATIONS OF SPECIALIST EVALUATION, EARLY GENOMIC ANALYSIS, AND SOME KIND OF MACHINE-ASSISTED LOOK. SO THAT'S PART OF THIS BURDEN OF DISEASE THING, WE'RE JUST GETTING STARTED TRYING TO DEVELOP ALGORITHMS AND PATTERNS, LOOKING AT IT THAT WAY. WE'VE ALSO BEEN TALKING TO A WHOLE LOT OF PEOPLE INCLUDING EXTERNAL STAKEHOLDERS, PEOPLE IN AUSTRALIA WHO HAVE BEEN LOOKING AT THIS, AND SOME OTHER U.S. PARTNERS ABOUT, YOU KNOW, LOOKING WITHIN THEIR HEALTH SYSTEMS AS WELL. IF WE CAN LEVERAGE SOME OF THESE SOURCES. SO, FOR EXAMPLE, YOUNG AGE HIGH COST UTILIZATION, MEDICAL SPECIALISTS, THERE'S PROBABLY SOMETHING GOING ON THERE. SO THE WAY CLINICAL PRACTICE IS NOW YOU SEE A PATIENT EVERY FIVE MINUTES, MAYBE BE GOING TO URGENT CARE, TELEMEDICINE THERE, PEDIATRICIAN THERE. ONE PERSON MAY NOT SEE IT, BUT THE SYSTEM CERTAINLY WOULD. SO CAN YOU BUILD THAT INTO WHAT WE'RE CALLING THE ZEBRA TRIGGER, SOMETHING THAT WOULD ESCALATE PEOPLE FASTER? THERE'S ANOTHER EXCITING THING, FACIAL RECOGNITION SOFTWARE, IS THERE SOMEBODY WHO SHOULD BE ESCALATED, THERE'S THESE AUGMENTED REALITY THINGS, GET A GAIT AND PUT OBJECTIVE DATA AROUND IT. ALL THIS STUFF GOING ON. CAN WE TRY TO BRING IT TOGETHER TO TRY TO HAVE THIS MULTI-DISCIPLINARY OR INTEGRATED APPROACH. PRESENTED A CONCEPT LAST COUNCIL, AND WE'RE WORKING ON THAT, BUT WE DO HAVE A NUMBER OF THINGS GOING ON RIGHT NOW BUT REALLY EARLY IN THIS DATA ANALYSIS. I MEAN, I THINK WE'RE GOING TO COVER SOME THINGS, AT LEAST GET US STARTED. DID YOU WANT TO ADD -- >> REMIND PEOPLE OF THE CODING PROBLEM. >> OH, YEAH. >> THEY MAY NOT REALIZE -- YEAH. >> WHEN YOU LOOK IN, FOR EXAMPLE, INSURANCE DATA BASE, OFTEN PEOPLE ARE GOING BY THE IDC 9 OR NOW 10 CODES, SOON TO BE 11 CODES. A LOT OF DISEASES DON'T HAVE CODES. SO OUR PATIENTS HAVE ESSENTIALLY SILENT IN THERE. IF YOU'RE JUST LOOKING BY CODE WE'LL MISS A BIG CHUNK OF OUR PATIENTS. IT HAS TO BE MULTI-ALGORITHMIC WAY OF LOOKING AT THIS DIFFERENT WAYS. >> SO ONE OF THE -- I WAS THINKING ABOUT REAL WORLD EVIDENCE, I'VE BEEN WORKING OVER THE LAST YEAR WITH THE CERNER HEALTH DATABASE, WHICH I WAS THINKING THAT WOULD BE COOL IF YOU COULD SEARCH DIFFERENT DISEASES, WE'VE DONE SOME FASCINATING THINGS WITH THAT. BUT IT'S ALL DE-IDENTIFIED. AND SO THAT'S THE CHALLENGE. YOU COULD FIND OUT PERHAPS WHAT THE INCIDENCE IS BUT YOU COULDN'T FIND THE PEOPLE WHICH IS PART OF THE CHALLENGE.& ANOTHER THOUGHT, AS YOU MENTIONED EARLIER, YOU'RE COMING UP WITH NEW DISEASES ALL THE TIME. I'M ASSUMING A LOT OF THEM THROUGH GENETIC TYPE OF ANALYSIS. IF YOU HAD A PLACE WHERE PEOPLE COULD, EVEN IF THEY DON'T KNOW WHAT IT IS, SUBMIT GENETIC RESULTS, AND YOU HAD A WHOLE BUNCH OF DIFFERENT, YOU KNOW, GENETIC RESULTS, NEW THINGS ARE IDENTIFIED, YOU COULD GO, OH, WELL, THIS IS ACTUALLY WHAT YOU HAVE. I MEAN, AGAIN, JUST TRYING TO THINK OF DIFFERENT WAYS TO INCREASE THE DIAGNOSTIC POOL VERSUS INCIDENCE POOL. >> THE THING TO CONSIDER WORKING WITH GOOGLE HEALTH, SEARCH PATTERNS, BECAUSE THEY HAVE MADE A LOT OF PROGRESS RELATED TO IDENTIFY PEOPLE WITH DISEASES THROUGH SEARCH PATTERNS. >> AND I MISSED FIVE MINUTES OF THE DISCUSSION, MAY HAVE MISSED ANY MENTION OF NEWBORN SCREENING, BUT IF I DIDN'T, WOULD YOU SAY THAT UNTIL WE CAN VASTLY EXPAND OUR ACCESS TO NEWBORN SCREENING WE'LL BE HAVING THIS DISCUSSION INTERMINABLY. WE'VE GOT THE CIRCULAR ARGUMENT, SO MANY OF US HAVE TROUBLE GETTING INVOLVED, GETTING INVOLVED IN CLINICAL RESEARCH, YOUNGER AND YOUNGER PATIENTS BECAUSE WE DON'T KNOW WHO THEY ARE. SO WE CAN'T GET THERAPY UNTIL, YOU KNOW, WE GET THAT WINDOW, THAT TREATMENT WINDOW WIDER. AND WE CAN'T IDENTIFY THOSE PATIENTS UNTIL WE CAN'T GET NEWBORN SCREENING UNTIL WE HAVE A TREATMENT, SO, YOU KNOW, IT'S CIRCULAR. AND SO I THINK UNTIL WE -- WOULDN'T IT BE WONDERFUL IF WHOLE GENOME SEQUENCING WAS THE NEWBORN SCREENING PARADIGM AND WE ANSWERED ALL THESE QUESTIONS IN ONE FELL SWOOP. >> THERE ARE ACTUALLY A COUPLE THINGS GOING ON FOR THE CTSA PROGRAM. PEOPLE HAVE MORE KNOWLEDGE ABOUT. DUKE HAS BABY'S FIRST TEST OR SOMETHING? >> THAT'S THE EARLY CHECK. THAT'S A PREVIOUS -- WE FUNDED IT A COUPLE YEARS AGO, IT WENT LIVE LAST FALL. AND AS RON POINTED OUT, THE ISSUE WITH A LOT OF PRENATAL SCREENING IS THAT WE SCREEN FOR THINGS WE CAN TREAT BUT IF WE DON'T TREAT, WE DON'T SEE ANY POINT IN SCREENING. IF WE DON'T SCREEN WE WON'T BE ABLE TO IDENTIFY PEOPLE WHO WOULD BE ELIGIBLE TO BE TESTED FOR A PARTICULAR THERAPEUTIC. EARLY CHECK WAS AN APPROACH THAT THE THREE NORTH CAROLINA CTSAs IN CONJUNCTION WITH STATE DEPARTMENT OF HEALTH PUT FORTH, WHERE PARENTS CAN -- ARE ASKED IF THEY WOULD LIKE TO BE PART OF. IT'S A PART OF THE NORMAL PRENATAL TESTING, IF THEY WOULD BE WILLING TO HAVE ADDITIONAL TESTS DONE. INTERESTINGLY NONE ONE THEY HAD CHOSEN BEFORE THE LICENSURE WAS FOR SPINAL MUSCULAR ATROPHY, INTERESTINGLY ENOUGH, BUT THEY CHOSE THAT AND FRAGILE X AS TWO TO BEGIN WITH BUT THE IDEA IS TO SEE WHETHER YOU CAN GET ENOUGH PEOPLE TO OPT IN OVER TIME TO ACTUALLY BEGIN TO ACCUMULATE AND VALIDATE THE TESTING SO THAT WHEN A TREATMENT DOES BECOME POTENTIALLY AVAILABLE, EVEN AT AN EXPERIMENTAL STAGE, YOU WOULD HAVE IDENTIFIED PATIENTS FROM AS EARLY AS POSSIBLE >> YEAH, I WANTED TO MAKE A COMMENT ABOUT SENSE YOU'RE COLLECTING INFORMATION INPUT, AND IT'S ON THE RECORD AND THERE'S BEEN SOME PRETTY STRONG FEELINGS ABOUT GLOBAL IDENTIFICATION AND ACTUALLY IDENTIFYING INDIVIDUAL PATIENTS, BASED ON MEDICAL INFORMATION, THAT YOU HAVE ACCESS TO, THROUGH A DATABASE, I WOULD LIKE TO GO ON THE RECORD WITH A DISSENTING VIEW TO SAY I UNDERSTAND THAT VERY MUCH IN THE CONTEXT OF RARE DISEASE. I COULD UNDERSTAND WHY PEOPLE WOULD EVEN VERY HAPPILY REVEAL THEIR IDENTITY, BUT THERE ARE PLENTY OF DISEASES THAT IN THE SOCIETY THAT WE LIVE IN IT IS NOT IN THE PATIENT'S BEST INTEREST TO HAVE THOSE DISEASES IDENTIFIED. I THINK IF ANY OF THE PRESIDENTIAL CANDIDATES HAD THEIR HEALTH RECORDS ACT, IT TURNED OUT THEY HAD PSYCHIATRIC ISSUES IN THE PAST, I WOULD IMAGINE THAT WOULD HAVE VERY BIG IMPACT IN TERMS OF GLOBAL IDENTITY. I THINK WE'RE FORGETTING THERE ARE PARTS OF THE WORLD WHERE INFORMATION ABOUT YOUR ETHNIC GROUP, YOUR RELIGION OR SEXUAL ORIENTATION CAN ACTUALLY BE FATAL PIECES OF INFORMATION. AND IN THIS GENOMIC ERA, EVEN IF DOING IT VOLUNTARILY, BUT AS SOON AS YOU ALSO HAVE ACCESS TO AN INDIVIDUAL, YOU ACTUALLY CAN FIND OUT THE WHOLE FAMILY. AND THERE WAS A VERY NICE DEMONSTRATION OF THIS BY THE WHITEHEAD -- BY THE BROAD INSTITUTE, ABOUT THREE YEARS AGO WHERE THEY USED PUBLIC DATABASES AND THEY IDENTIFIED ONE PERSON, AND THEN BASED ON THE GENETIC DATABASES THEY WERE ABLE TO GET ALL THE RELATIVES, MANY RELATIVES. SO I JUST DON'T THINK -- IT'S NICE TO SAY, GEE, IF WE COULD PROTECT THESE DATABASES, THEN EVERYTHING WOULD BE FINE. BUT WE'VE HAD EVERY MAJOR RETAILER IN THE UNITED STATES, WE'VE HAD THE SWISS BANKS, WE'VE HAD THE NATIONAL SECURITY AGENCY OF THE UNITED STATES HACKED. SO, UNLESS -- I DON'T SEE A GUARANTEE FOR PROTECTION OF THAT DATA YET. AND I PERSONALLY BELIEVE IT WILL BE A LONG TIME COMING. >> I DID NOT SET THAT UP WELL. IN THE CONTEXT I WAS SPEAKING GLOBAL UNIQUE IDENTIFIER WOULD BE CREATED BASED ON DATA THAT SOMEONE VOLUNTARILY PUTS INTO OUR REGISTRY. SO IT HAS -- WELL, THE FIRST OF THE SEVEN I KNOW OF, THERE WAS ONE A WHILE AGO, NOW THERE'S A LOT MORE, IT WAS AN ALGORITHM THAT NEEDED FIRST NAME, MIDDLE NAME, CITY OF BIRTH, SEVEN THINGS. AND IF YOU PUT THOSE SEVEN THINGS IN, ANY DIFFERENT REGISTRY, THE ALGORITHM SHOULD COME UP WITH THE SAME UNIQUE IDENTIFIER. SO THERE WAS NO IDENTIFYING NAME OR BIRTH DATE OR ANYTHING LIKE THAT. THE PROBLEM WAS THERE WERE GLITCHES. IF YOU PUT IN NEW YORK, NEW YORK, YOU GOT ONE ALGORITHM RESULT. IF YOU PUT IN NEW YORK NY, IT MIGHT BE SLIGHTLY OFF. SO ON. YOU CAN SEE HOW THAT WOULD GO DOWN. SO THAT MADE ONE ALGORITHM NOT PERFECT BUT OKAY. AND THEN OTHER GROUPS, CHRIS CAN TALK TO THIS BETTER, DECIDED THEY WERE GOING TO COME UP WITH THEIR OWN ALGORITHM. THERE'S NO LONGER A GLOBAL UNIQUE IDENTIFIER. THERE'S SEVERAL DIFFERENT ONES. BUT THIS IS SOMETHING THAT WHEN OUR FAMILY SIGNED THE CONSENT THEY WERE CONSENTING TO, AND IT WAS FOR THE PURPOSE OF DE-IDENTIFYING THEIR DATA. I UNDERSTAND AND AGREE WITH YOUR POINT ABOUT, YOU KNOW, EVERYBODY BEING ABLE TO BE IDENTIFIED, BUT THIS IS WAS REALLY TO PREVENT DE-IDENTIFIED DATA BEING SEEING AS MULTIPLE PATIENTS WHEN IN FACT IT WAS JUST ONE. >> WE WERE TALKING ABOUT THIS YESTERDAY. I THINK WHAT WOULD BE USEFUL IN THE LAST TEN MINUTES OR SO IS TO HELP US PRIORITIZE ALL THE REALLY GREAT THINGS THAT YOU'VE ALL SUGGESTED, AND WE'VE -- THERE WAS A REPORT THAT JUST CAME OUT YESTERDAY. FROM SOMETHING CALLED THE CENTER FOR DATA INNOVATION, THAT'S RAISING THIS GOOD QUESTION AGAIN. NOTHING TO DO WITH RARE DISEASES. HAVING TO DO WITH THE HEALTHCARE SYSTEM IN GENERAL. AND SO WE'RE TRYING TO FIGURE OUT, YOU KNOW, IS THIS -- IS THIS WORTH DOING? SHOULD WE SPEND TIME DOING? IS THIS GOING TO BE A QUEST WHICH IS JUST NOT GOING TO GO ANYWHERE SO WE SHOULDN'T WASTE TIME OR SHOULD WE PURSUE IT? I HAVE -- WE HAVE MANY OF THE SAME QUESTIONS WITH NEWBORN SCREENING. YOU KNOW, IT'S OCCURRED TO US THAT, YOU KNOW, THAT THE DIAGNOSTIC ODYSSEY IS NAMED AFTER A GUY NAMED ODYSSEUS, AND THE EASIEST WAY TO DIAGNOSE RARE DISEASE PATIENTS IS TO PREVENT THEM FROM LEAVING ITHACA IN THE FIRST PLACE, THEY DON'T TAKE TEN YEARS TO GET HOME. AND YET THEY ARE ALL THERE. TO DO WHOLE GENOME SEQUENCING COSTS ABOUT THE SAME AS HIGH LEVEL MRI. AND YET WE DON'T DO IT. AND BUT ON THE OTHER HAND THERE ARE ALL KINDS OF FORCES IN THE OTHER DIRECTION WITH THAT WE'VE RUN INTO, SO SHOULD WE RISK BREAKING OUR SWORDS ON THAT ONE, OR IS THAT ANOTHER, YOU KNOW, QUIXOTIC PURSUIT THAT'S A GREAT THING BUT WE SHOULDN'T SPEND LIMITED TIME ON IT, OR SHOULD WE? SHOULD WE PUT MORE EMPHASIS ON THE PLATFORM? LIKE WHAT BRAD MENTIONED ABOUT THE ASO, SAME KIND OF THING WE'RE DOING IN GENE THERAPY OR -- SO IT WOULD BE REALLY -- THIS IS A HARD QUESTION, BUT WHERE DO YOU THINK -- IF WE HAD ANOTHER -- WHICH WE DON'T, LET'S SAY WE HAD ANOTHER $5 MILLION THAT I COULD GIVE ANNE WHICH I WOULD LOVE TO HAVE, WHAT WOULD BE YOUR ADVICE WHAT SHE SHOULD DO WITH IT? SHOULD WE FUND ANOTHER COUPLE RDCRN CENTERS? SHOULD WE FOCUS MORE ON -- SHOULD WE DO A NEW THING? WHAT WOULD YOUR ADVICE BE? >> ONE, I WAS REMISS NOT TO SAY, AS A DISEASE INVOLVED IN RDCRN IT'S A PHENOMENAL PROGRAM. WE HAVE CLINICAL SITES. WE DON'T HAVE ANYBODY THAT WANTS TO MAKE A DRUG FOR US BUT WE HAVE CLINICAL SITES UP AND READY, WE'LL BE READY TO GO WHEN THEY ARE. THERE'S SO MANY WONDERFUL THINGS ABOUT IT. BUT YOU HAVE 20. AND THAT'S -- WE'RE ONE OF THREE DISEASES BUT IT'S JUST NOT SCALING. SO, I THINK ADDING $5 MILLION TO THAT WOULD BE -- IT'S NOT GOING TO MAKE THE DENT. I THINK THE ALGORITHM WHICH WHEN PCORI MANDATED FOR US, COMPUTABLE PHENOTYPE IT WAS CALLED, IS GREAT EXCEPT THAT WITHOUT IDC 10 CODES, THEY ARE STILL TRYING TO FIGURE OUT THE DISEASE AND MUTATIONS, IF YOU PUT IN EPILEPSY, NEUROLOGY, SLEEP MEDS, G.I. WORKUP, ALL THAT, YOU'RE GOING TO GET 50 SYNDROMES THAT LOOK ALIKE WITHOUT A GENETIC TEST. SO, WITH THE LEAST AMOUNT OF MEDICAL AND SCIENTIFIC KNOWLEDGE AT THIS TABLE, MY VOTE WOULD BE ANYTHING THAT INCREASES GENETIC TESTING. >> OR IDENTIFICATION OF PATIENTS, GENERALLY. YOU KNOW, WOULDN'T NECESSARILY BE A GENETIC TEST BUT ANY -- >> ANYTHING THAT FINDS PATIENTS FASTER, CHEAPER, YOUNGER, SOONER. IF WE GET TREATMENTS WE HAVE TO DO CLINICAL TRIALS. YOU'LL RUN OUT OF PATIENTS. >> I TEND TO LEAN TOWARDS A THERAPY THAT -- A REAL DEMONSTRATION. I THINK WE HAVE ONLY ONE GENE THERAPY APPROVED NOW, MAYBE I'M WRONG. AND IT SEEMS TO ME THAT IF YOU -- YOUR TEAM I NTERNALLY WENT THROUGH A COMPREHENSIVE EXERCISE LOOKING AT THE INFORMATION THAT YOU HAVE, AND I THINK ONLY -- THERE WOULD BE ONLY A FEW INSTANCES RIGHT NOW WHERE YOU COULD ACTUALLY MAKE A MOVE, YOU COULD CONSTRUCT SOMETHING AND GO IN THERE AND DO SOMETHING, FOLLOWING A PATHWAY THAT WE'VE LEARNED THROUGH AN FDA APPROVAL. THE IMPACT OF THAT WOULD BE VERY LARGE AND OPEN THE DOOR FOR A LOT. THERE'S-- IT WOULD PROBABLY RESULT IN GETTING FUNDS TO GET MORE INFORMATION. I JUST THINK WE'RE COLLECTING SO MUCH INFORMATION. YOU'VE EMPHASIZED THE BEGINNING OF TODAY'S MEETING TRANSLATION. AND THAT THAT'S WHAT WE'RE ABOUT. AND THAT'S, YOU KNOW, THAT'S THE GOAL. SO I WOULD LOOK AND SEE IF THERE'S A PRACTICAL MOVE THAT COULD BE MADE FOR ONE OR VERY SMALL NUMBER NOW AS THE VANGUARD, AND THEN I THINK OTHER THINGS MIGHT (INDISCERNIBLE). [APPLAUSE] >> YOU ALL DID GOOD. WE'RE RIGHT ON TIME. THAT'S UNBELIEVABLE. THAT'S HELPFUL. THANK YOU. EXACTLY THE DISCUSSION WE WANTED TO HAVE. OKAY. SO I THINK WE ARE GOING TO MOVE ON TO CONCEPT CLEARANCES. SO ANNA, I THINK YOU'RE GOING TO DO THESE? REMIND PEOPLE WHAT A CONCEPT CLEARANCE IS AND WE CAN GO TO THOSE TOO >> YES. SO, BEFORE, IN GENERAL, BEFORE WE COMMIT FUNDS OR EFFORT TO PURSUING A PARTICULAR INITIATIVE WE WANT FEEDBACK FROM MEMBERS OF ADVISORY COUNCIL. CONCEPT CLEARANCE SPEAKS TO THAT SORT OF ACTIVITY. THE NATURE OF THE ACTIVITY, ITS- SPEAKS TO HISTORY, IMPORTANCE, AND WE GENERALLY ASSIGN TWO OR MORE MEMBERS TO BE DISCUSSANTS. WHAT'S GOING TO HAPPEN NOW IS ALICE IS GOING TO PRESENT A CONCEPT OR IDEA FOR INITIATIVE THAT WE SHOULD UNDERTAKE AND WILL ASK THE DISCUSSANTS TO CHIME IN AND EVERYBODY WILL HAVE A CHANCE TO DISCUSS THE CONCEPT AS PRESENTED AND THEN WE'LL VOTE ON WHETHER OR NOT WE SHOULD GO FORWARD WITH THAT CONCEPT. ALICE? >> ALICE, IS THAT MIC ON? WE'RE NOT HEARING YOU. >> I'LL BE BE TALKING TO CONTINUING TO PUSH THE MESSAGE RARE DISEASES ARE NOT RARE WHEN CONSIDERED COLLECTIVELY. I'LL BEGIN WITH SOME CONTEXT ON WHAT WE MEAN BY THE SLOGAN THAT RARE DISEASES ARE NOT RARE. AS YOU HEARD WHEN THOUGHT ABOUT INDIVIDUALLY, EACH RARE DISEASE IS RARE AND AFFECTS FEWER THAN 200,000 PEOPLE IN THE UNITED STATES. HOWEVER, WHEN ABOUT 7,000 RARE DISEASES ARE CONSIDERED COLLECTIVELY, THEY AFFECT 30 MILLION PEOPLE IN THE U.S. THE WORD "RARE" IS MISLEADING AND EVEN HARMFUL TO THE COMMUNITY. IT MIGHT IMPLY THE DISEASES ARE OF LESSER IMPORTANCE, THEY DO NOT MATTER, THEY DON'T AFFECT ME, AND THUS CAN BE DISMISSED, OR RECEIVE LIMITED RESOURCES. CONSIDER CANCER. IT IS VIEWED AS ONE LARGE PROBLEM EVEN THOUGH THERE ARE THOUSANDS OF CANCERS. EVEN THE WORD "CANCER" IS SINGULAR AND NOT PLURAL. WE WANT THE PUBLIC TO THINK ABOUT RARE DISEASES IN THE SAME WAY AND CHANGE THE PERCEPTION OF RARE. THERE IS ROOM FOR IMPROVED COLLABORATION WITHIN THE COMMUNITY, AND FOCUS ON RARE DISEASES BY FINDING COMMONALITIES. LAST YEAR THE FIRST RARE DISEASES PRIZE COMPETITION AT NIH OPENED. SORRY, AT NCATS OPENED AND WE RECEIVED ALMOST 50 ENTRIES. THE CHALLENGE WAS DIRECTED AT THE NON-SCIENTIFIC MEMBERS OF THE PUBLIC, TO SUBMIT WORKS OF ART PROMOTING MESSAGE THAT RARE DISEASES ARE NOT RARE AND AFFECT A RATHER SUBSTANTIAL PROPORTION OF PEOPLE IN THE U.S., MANY OF WHOM ARE CHILDREN. AS YOU CAN SEE HERE, WORKS OF ART COULD INCLUDE SEVERAL TIMES OF ORIGINAL CREATIONS EASILY COMPREHENSIBLE. FIRST WAS SUCCESSFUL INCREAING PUBLIC AWARENESS ABOUT RARE DISEASES AND THEIR COLLECTIVE IMPACT. PEOPLE FROM ALL OVER THE WORLD AND WITH DIFFERENT BACKGROUNDS CONTACTED US TO ENTER THE PRIZE COMPETITION. AND OUR 2019 RARE DISEASE DAY AT NIH WAS THE HIGHEST ATTENDED IN THE EVENT'S HISTORY. THE FIRST EVER AWARDS WERE PRESENTED TO THE WINNERS, AND DISTINGUISHED MISSIONS ON DISPLAY THE WHOLE DAY. NCATS CHALLENGE WEB PAGES HAD THOUSANDS OF VIEWS WITH MOST TRAFFIC IN JANUARY AND FEBRUARY DURING OUR RARE DISEASE CAMPAIGN. BUT VIEWS ALSO CONTINUED THROUGH MARCH. AND AN NCATS DIRECTOR'S MESSAGE WAS RELEASED TO CONTINUE PUSHING THIS COLLECTIVE RARE DISEASE MESSAGE AND ITS OVERALL BURDEN ON SOCIETY. SOME OF YOU HAVE THE ACTUAL POSTERS IN FRONT OF YOU, WINNING POSTER, FIRST PLACE WINNER SUBMITTED A SERIES OF INFO GRAPHICS LIKE THIS ONE, VARIOUS FORMATS AND LAYOUTS. AND THIS HELPED WITH DISSEMINATION, DEPENDING ON US ON A. SHE PLACED STRIKING FACTS ON THE TILES USING CREATIVE THEME SO THE MESSAGE WOULD STICK. AND ADDING A LITTLE BIT OF HUMAN IN THE FINE PRINT, THE BURDEN OF RARE DISEASES IS DRIVEN HOME WHEN SHE STATES 30 MILLION PEOPLE IN THE USA HAVE A RARE DISEASE, THERE ARE NO UNICORNS LIVING IN THE USA. AND MOST OF US KNOW ABOUT UNICORNS. POSTERS, LIKE THESE, STARTED MANY CONVERSATIONS AND WERE SUCCESSFUL AND INCREASING AWARENESS. AND WE CONTINUE TO GET REQUESTS TO DISSEMINATE POSTERS, TO THIS DAY. OUR SECOND PLACE WINNERS HAVE AN EQUALLY COMPELLING MESSAGE, AND I WILL LET THE VIDEO SPEAK FOR ITSELF, IT WILL PLAY FOR TWO MINUTES. >> I'M NOT SO SPECIAL. I DON'T FEEL RARE. YOU ALREADY KNOW SOMEONE LIKE ME, SOMEONE WITH A RARE DISEASE. BECAUSE ONE IN 10 PEOPLE HAVE A RARE DISEASE. THAT'S TWICE AS MANY AS CANCER. IF YOU PUT US ALL IN ONE STATE, WE WOULD BE THE SIZE OF TEXAS. IF ALL RARE DISEASE PEOPLE IN THE WORLD HAD OUR OWN COUNTRY WE WOULD GO BIGGER THAN AMERICA, OUR OWN SUPERPOWER. THE LAND OF RARE DISEASE. MAYBE WE SHOULD GO THERE, TO OUR LAND OF RARE DISEASE. AND LIVE WITH THE DISEASE NO ONE EVER HEARD OF, LIKE CRMO, OR SCLERODERMA, THAT'S MINE. AFTER WE MAKE 7,000 VILLAGES, WE MAKE MORE FOR THE RARE DISEASES THAT DON'T EVEN HAVE NAMES. YET. WE WOULD DISCOVER THE SECRETS OF OUR DISEASES THE HIDDEN TREASURE. THEN WE WOULD TEACH THE REST OF THE WORLD WHAT WE KNOW, BECAUSE SECRETS AND SCIENCE OF RARE DISEASES HAVE BEEN BEHIND LIFE-SAVING MEDICINES AND ADVANCES. THE ENTIRE WORLD WOULD FINALLY KNOW US, SEE US, THANK US. AND WE WOULD SAY, YOU'RE WELCOME. THINGS WOULD BE BETTER IN THE LAND OF RARE DISEASE. ONE MORE THING ABOUT THE LAND OF RARE DISEASE, HALF OF US ARE CHILDREN. HERE IN THE REAL WORLD, LOTS OF US FEEL ALONE. HARDLY ANY OF US HAVE FDA TREATMENTS. WE CAN WAIT YEARS JUSTING TO DIAGNOSED. I'LL BE A DOCTOR SOMEDAY BUT TODAY HERE AND NOW WE NEED EVERYONE ELSE TO UP HAD. WE NEED RESEARCHERS, SPECIALISTS, PEOPLE WHO CARE ABOUT RARE DISEASE. WE ALL DESERVE THE CHANCE TO GET BETTER, EVEN NOT-SO-RARE KIDS LIKE ME. >> SO FOR THIS CONCEPT OUR MAIN GOALS WITH THE PRIZE COMPETITION TO CONTINUE RAISING AWARENESS IN THE GENERAL PUBLIC THAT RARE DISEASES ARE MORE COMMON THAN CURRENTLY BELIEVED, AND TO CHANGE THE PERCEPTION THAT RARE DISEASES DO NOT -- PERCEPTION THAT RARE DISEASES DO NOT WARRANT PUBLIC HEALTH PRIORITIZATION. THIS MAY INCLUDE DRAWING ATTENTION TO COMMON CHALLENGES, NEEDS, OR SOLUTIONS. OR HIGHLIGHTING NEED FOR RESEARCH AND DEVELOPMENT OF NEW TREATMENTS. AS STATED PREVIOUSLY, OVERARCHING GOAL IS TO CHANGE THE PUBLIC PERCEPTION OF RARE. WE ALSO WANT TO BUILD AND FOSTER COLLABORATIONS ACROSS THE COMMUNITY BY ENCOURAGING PEOPLE TO WORK COLLABORATIVELY, WHILE IN THE PROCESS OF DEVELOPING A WINNING ENTRY. AND EXPLORE MORE EFFECTIVE WAYS TO COMMUNICATE THE MESSAGE OF RARE DISEASE WHILE TRACKING PUBLIC INFLUENCE AND IMPACT. A FEW AREAS TO HIGHLIGHT DIFFERENT THIS TIME AROUND SUBMISSIONS WILL BE ENCOURAGED TO BE A PRODUCT OF COLLABORATING WITH OTHERS AND BREAKING DOWN BARRIERS OR SILOS. EXAMPLES COULD INCLUDE A PARENT-CHILD TEAM, CAREGIVERS OR SIBLINGS FROM DIFFERENT DISEASES, OR PATIENT RESEARCHER TEAM FOR MEASURING SUCCESS DEFINED AHEAD OF TIME SO THAT PUBLIC INFLUENCE AND IMPACT CAN BE BETTER TRACKED. AND LESSONS LEARNED FROM THIS COULD BE USED BY OUR OFFICE TO CONTINUE IMPROVING OUR REACH TO OUR TARGET AUDIENCE WITH MANY PUBLIC-FACING PROGRAMS. AND WITH APPROPRIATE CONSENT ENTRIES CAN BE DIRECTLY SUBMITTED BY CHILDREN. THE OUTCOMES OF THIS CHALLENGE WOULD BE SOME KIND OF CREATIVE MEDIA, A WAY TO COMMUNICATE AND EDUCATE OTHERS ABOUT RARE DISEASES, DESCRIPTION OF HOW THE SUBMISSIONS CAN MAKE THE MOST IMPACT, INCLUDING PROPOSED DISSEMINATION PLAN, FOLKS A FINAL ENTRY. THE POTENTIAL IMPACT IS INCREASED IN PUBLIC AWARENESS OF RARE DISEASES AS WELL AS COMMON CHALLENGES AND THEIR OVERALL BURDEN ASSOCIATED, CONTINUED FOCUS ON PATIENT INVOLVEMENT THROUGHOUT THE ENTIRE RESEARCH PROCESS, BUILDING NEW OR STRENGTHENING EXISTING COLLABORATIONS ACROSS DISEASES, ROLES AND POSITIONS, AND UTILIZATION OF THE SUBMISSIONS BY NCATS TO HELP PUBLIC THE MESSAGE THAT RARE DISEASES ARE NOT RARE, AND THE ONGOING NEED FOR MORE RESEARCH. SOME CRITERIA FOR EVALUATING THE SUCCESS OF THIS PROGRAM WOULD BE A GREATER NUMBER OF SUBMISSIONS RECEIVED AND THUS MORE PARTICIPATION, INCREASED VISITS TO THE CHALLENGE WEB PAGES, MORE ATTENTION ON SOCIAL MEDIA ABOUT RARE DISEASES AS A WHOLE, AND IT WOULD BE GREAT IF THIS CHALLENGE INCREASED COLLABORATIONS ACROSS SILOS, AND ENCOURAGED PEOPLE WHO DON'T TYPICALLY WORK TOGETHER TO SUBMIT AN ENTRY. A FEW OBSTACLES, FINDING WAYS TO STAND OUT, SIMILARITIES AMONG ALL DISEASES, BEING ABLE TO THINK OUTSIDE THE BOX AND BUILD RELATIONSHIPS TO TEAM ON AN ORIGINAL ENTRY AND THERE'S NO CLEAR WAY TO REALLY MEASURE IMPACT AND THE EFFECTIVENESS OF THIS TYPE OF MESSAGE. THERE ARE PATIENT ORGANIZATIONS THAT HAVE HELD THEIR OWN COMPOSITIONS OR HAVE HAD ART SHOWS OR USE OF SOCIAL MEDIA TO SPREAD A MESSAGE MORE BROADLY. HOWEVER, THOSE TYPICALLY FOCUS ON SINGLE INDIVIDUAL OR SPECIFIC RARE DISEASE. AND AS YOU HEARD EARLIER, OUR NCATS RARE DISEASE CLINICAL RESEARCH NETWORK, RDCRN, IS BUILD ON THE IDEA OF CLUSTERING DISEASES TOGETHER FOR RESEARCH AND INVOLVING THE PATIENT ORGANIZATIONS THROUGHOUT ALL STAGES. SO WE'VE ADOPTED THIS INTO THIS CONCEPT. AND AGAIN NCATS HAD A PRIZE COMPETITION IN 2018, AND FROM THIS SUCCESS OF THE SUBMISSIONS AND HIGH LEVEL OF INTEREST FROM THE PUBLIC, WE'RE PROPOSING A SECOND CHALLENGE TO NOT ONLY CONTINUE ENGAGING THE COMMUNITY WITH NIH BUT ALSO TO FOCUS ON COMMONALITIES BETWEEN THESE DISEASES AND CHANGE THE PUBLIC PERCEPTION OF RARE. THANK YOU. RON AND MEGAN? >> SO, I'LL TAKE THE FIRST CRACK. FIRST OF ALL, CONGRATULATIONS ON A TERRIFIC PROGRAM. I THINK ORDR SHOULD BE APPLAUDED FOR THE WONDERFUL RESOURCES THAT WERE DEVELOPED IN THIS PROGRAM LAST YEAR. I TOOK SOME TIME YESTERDAY AND WATCHED EACH OF THE WINNING AND EVEN THE HONORARY MENTIONS, AND JUST TERRIFIC RESOURCES. REALLY COMPELLING. SOME ORIGINAL MUSIC THAT WAS JUST REALLY IMPRESSIVE. SO, IT'S CLEAR THAT THE PROGRAM WAS ABLE TO DISCOVER AND DEVELOP REALLY POWERFUL RESOURCES. MY QUESTION IS ABOUT THE THIRD D, DISSEMINATE. YOU KNOW, THE ONLY PLACE I FOUND IT WAS ON THE NCATS WEBSITE. AND SO I'M GOING TO ENCOURAGE YOU TO WORK ON THE THIRD D AS MUCH AS POSSIBLE THIS INCOMING PHASE 2. I THINK ONE WAY WE COULD DO THAT IS LOOK AT THE TIME LINES. I LOOKED AT THE TIMELINES FOR THE LAST YEAR'S PROGRAM. THEY SAME WAY TOO RUSHED. THESE ENTRIES WOULD BE IN BY THE END OF NEXT MONTH, SIX WEEKS AWAY, FIVE AND A HALF WEEKS AWAY. AND ANNOUNCEMENTS MADE BY I THINK NOVEMBER. AND THEY WOULD BE AWARDED AT RARE DISEASE DAY. MY SUGGESTION IS LET'S BACK THAT UP AND REALLY DO A POWERFUL JOB OF THE DISSEMINATION, AND USE THE RARE DISEASE DAY TO LAUNCH THE PROGRAM. AND GET ALL THAT ENTHUSIASM GOING ON RARE DISEASE DAY. AND PUSH THE SUBMISSIONS AND THE ASSESSMENTS, EVALUATIONS, LATER INTO THE COMING YEAR. AND IN THE MEANTIME, THE TEAM WOULD WORK ON THE DISSEMINATION PLAN, ESTABLISH RELATIONSHIPS WITH, YOU KNOW, NON-RARE DISEASE COMMUNITIES BECAUSE THESE ASSETS, THESE RESOURCES SO FAR IN MY VIEW, I DON'T KNOW MUCH ABOUT IT, WE'RE TALKING TO OURSELVES. RESOURCES DEVELOPED BY RARE DISEASE PATIENTS AND ADVOCATES, AND BEING VIEWED BY RARE DISEASE PATIENTS AND ADVOCATES WE NEED TO PUSH IT OUT INTO THE PUBLIC AND THERE ARE WAYS TO DO THAT. COMMUNICATING WITH COMMUNICATIONS NETWORKS, TELEVISIONS, TELEVISION PROGRAMS, CHORALE GROUPS TO PERFORM THE WONDERFUL MUSIC ELEMENTS, THAT SORT OF APPROACH I THINK WE WOULD TAKE THIS POWERFUL -- THESE POWERFUL RESOURCES TO A MUCH BROADER AUDIENCE. >> WHAT WAS THE TOTAL -- THE FIRST PRIZE WAS $5,000. THE TOTAL COST FOR THIS? >> COST WAS $5,000. THE FIRST PLACE WAS $3,000, WITH I THINK WE TRAVELED FOUR PEOPLE TO THE RARE DISEASE DAY LAST YEAR. >> WHICH IS GREAT BUT A LOT CHEAPER THAN HAVING TO -- YOU KNOW, GIVE IT TO RESEARCHERS. KIDS IN SCHOOLS ARE APPRECIATIVE OF EVERY LITTLE PENNY. I AGREE WITH RON ABOUT PREACHING TO THE CHOIR. I MEAN, IT'S THE SAME USUAL SUSPECTS THAT GO TO THESE MEETINGS AND THAT ARE ON LISTSERVS, AND IT WOULD BE GREAT TO JUST KEEP GETTING THAT MESSAGE OUT, IS IT ONE IN FIVE OR ONE IN TEN PEOPLE HAVE RARE DISEASE? ONE IN TEN, OKAY. AND TO GET THAT OUT NATIONALLY. THERE ARE LOTS OF ATHLETES WITH RARE DISEASE, LOTS OF CELEBRITIES WITH RARE DISEASES, AND IF THEY WOULD, YOU KNOW -- THE ONES WILLING TO ADMIT TO WHAT THEY'VE GOT, HELP GET THAT MESSAGE OUT OF ONE IN TEN, ONE IN TEN. AND I THINK THE IDEA OF AIMING THIS TOWARDS CHILDREN IS GREAT, YOU KNOW, KIDS GET -- THEY LEARN THINGS WHEN THEY ARE YOUNG AND THEY HOLD ONTO IT. ONE OF THE MOST ACTIVE PEOPLE I'VE MET IN THE DUCHENNE MUSCULAR DYSTROPHY CAMP IS THE CAMP COUNSELOR, SHE MADE IT HER CAREER. IT'S GREAT. IT'S FUN. I THINK THE TURNAROUND PERIOD WAS REALLY QUICK. THE DOWN SIDE TO DOING THIS BIG IS YOU'LL HAVE A LOT MORE ENTRIES BUT, YOU KNOW. GETS SOME RARE DISEASE PEOPLE TO HELP YOU JUDGE 'EM. BUT I MEAN I THINK IT'S WONDERFUL. IT'S A MINUSCULE AMOUNT OF MONEY COMPARED TO OTHER THINGS THIS TABLE DECIDES ON. I DON'T WANT TO OVERTHINK IT. >> I THOUGHT THE EXAMPLES YOU SHOWED US WERE REALLY TERRIFIC. AND I REALLY LIKE THE PROGRAM. BUT I THINK YOU'VE GOT TWO GOALS HERE, ONE IS TO KIND OF GET THE COMMUNITY, THE BROAD COMMUNITY RALLIED AROUND THE FLAGPOLE HERE. AND THE OTHER IS TO INCREASE AWARENESS ON THE NATIONAL LEVEL. AND THOSE TWO, IT'S NOT CLEAR TO ME THAT RALLYING THE COMMUNITY IS THE OPTIMAL WAY TO DISSEMINATE TO THE WHOLE COUNTRY AND MAYBE YOU'RE RUNNING INTO THAT. SO I'M JUST IMAGINING DIFFERENT WAYS, IF YOU DIDN'T PUT THE CONSTRAINT THAT THE PRODUCT HAD TO COME FROM THE COMMUNITY, AND SAID WE JUST WANT THE BEST PRODUCT TO DISSEMINATE THE MESSAGE OF ONE IN TEN, AND GET IT IN THE NATIONAL CONSCIOUSNESS, YOU MIGHT CHOOSE IN THE FUTURE A DIFFERENT ROUTE, FOR INSTANCE MAKING THIS UP, YOU COULD APPROACH THE BIGGEST AD AGENCIES IN THE UNITED STATES, AND ASK THEM FOR PRO BONO WORK. WOULD YOU TAKE THIS ON? I DON'T KNOW IF IT'S A GOOD IDEA OR NOT BUT THEY HAVE A DIFFERENT SKILL SET AND DIFFERENT EXPERTISE THAN WHAT WE'RE DOING HERE. OR THERE MIGHT BE SOME BLEND. GOING FROM WHERE WE ARE NOW TO WHAT I'VE SEEN GETTING DISSEMINATION GOAL, I THINK THAT'S VERY CHALLENGING. >> I'LL COMMENT WE AGREED WE WANTED TO NOT HAVE TOO MANY CONSTRAINTS. WE LIFTED -- LAST YEAR WE HAD THAT YOU HAD TO BE 18 YEARS OLD OR OLDER TO SUBMIT BUT THIS YEAR WE'VE GOTTEN RID OF THE BOTTOM AGE LIMIT CONSTRAINT AS LONG AS IT'S APPROPRIATE CONSENT. CONSTRAINT ABOUT WHO CAN APPLY, WE DIDN'T REALLY LIMIT THAT ACTUALLY SO ANYBODY COULD HAVE COME IN. WE HAPPENED TO HAVE A LOT OF INTEREST FROM MORE OF THE LAY COMMUNITY, PEOPLE THAT HEARD, ORD OF MOUTH, THOUGHT IT WAS A FUN THING TO PARTICIPATE. WE AGREE AND WE'LL MAKE SURE WHEN WE WRITE THE WORDING FOR IT THAT WE KEEP IN MIND SOME OF THE POTENTIAL CONSTRAINTS. >> YOU MIGHT PROACTIVELY APPROACH, YOU KNOW, ORGANIZATIONS WITH DIFFERENT KIND OF -- >> AT THE RISK OF BEING -- WHAT YOU HAVE DONE WITH THE CAMPAIGN IS FANTASTIC, A MODEL HOW TO STRETCH MONEY, AMAZING, BANG FOR THE BUCK. NO DOUBT. WE NEED TO HAVE YOU WORK ON OTHER THINGS, BY THE WAY. BUT -- SO I'M OBVIOUSLY PASSIONATE ABOUT RARE DISEASES. I AM ON THE BOARD OF GLOBAL GENES, SUMMIT TOMORROW WITH 800 ADVOCATES TOMORROW, USED TO BE ON THE BOARD OF GENETIC ALLIANCE, THAT'S AN UMBRELLA ORGANIZATION, FOUGHT JUST FOCUSED ON MY KIDS DISEASE ORGANIZATION. MY ONLY POINT IS AMAZING AWARENESS FOR RARE DISEASE STILL INTERIM ENDPOINT. AND THE BUSINESS WORLD IF YOU HAD DONE AN AMAZING JOB, YOUR PRODUCT HAS AMAZING AWARENESS, EVERYDAY HOUSEHOLD WORD, BUT PEOPLE DON'T BUY IT, THEN YOU STILL FAIL AND GET FIRED AS THE EXECUTIVE, RIGHT? WHAT IS IT WE'RE GETTING BY HAVING AWARENESS? I GUESS THE COMMUNITY CAN FEEL GOOD ABOUT THEMSELVES. YOU'RE NOT ALONE, THAT'S A GOOD THING. BUT IT STILL ISN'T THAT SATISFYING TO ME, I HAVE TO SAY. IT'S WEIRD FOR ME TO BE THE ONE SAYING THAT, MY TWO SONS DON'T CARE THAT MUCH THAT MORE PEOPLE KNOW ABOUT RARE DISEASES, THEY WOULD LIKE TO BE ABLE TO DO MORE THINGS WITH THEIR BODIES THAT THEY CAN'T. SO TELL ME WHAT IS THE NEXT THING AWARENESS GETS US? DOES IT GET CONSTITUENTS TO GO TO CAPITOL HILL AND INSIST ON A SET-ASIDE THAT GIVES A BILLION DOLLARS TO RARE DISEASE? OR DOES IT SOMEHOW MAKE IT EASIER TO RECRUIT INVESTIGATORS FOR TRIALS OR RESEARCHERS? YOU KNOW, ANY OF THOSE THINGS ARE POSSIBLE BUT I'M A LITTLE UNCOMFORTABLE ONLY FOCUSING ON THE AWARENESS, I'M NOT THAT CERTAIN THAT JUST BECAUSE EVERYBODY KNOWS THE TAG LINE THAT EVERYWHERE I GO RIGHT NOW PEOPLE WILL SAY, YOU KNOW, ONE OF OUR 50 MILLION PEOPLE WITH RARE DISEASE, THAT'S GREAT, BUT EVEN THE INDUSTRY NOW, IT'S BEEN AN AMAZING FEW YEARS. I WAS WITH TAKADA YESTERDAY, IF YOU WANT TO SELL, FOCUS ON RARE DISEASES, THEY WILL TAKE YOUR CALL. FUNDS ARE SPECIFICALLY FOCUSED ON TRYING TO ONLY FOCUS ON RARE DISEASE COMPANIES. THEY DON'T NECESSARILY MEAN ULTRA RARE UNFORTUNATELY BUT IT'S ALL ABOUT RARE. RARE IS REALLY HOT. BECAUSE OF THINGS LIKE THIS WE'RE GETTING AWARENESS, BUT I'M JUST -- I HAVE TO SAY WE STILL NEED THAT OTHER PIECE, AND SO IF YOU'RE ALLOCATING RESOURCES THIS IS SO EFFICIENT AND FRUGAL, I AM IN SUPPORT OF IT, BUT IN GENERAL THIS UMBRELLA OF SAYING RARE, RARE, RARE ISN'T FLOATING MY BOAT THAT MUCH BECAUSE I'D LOVE TO HAVE ONE MORE ASO FOR KIDS OR ONE MORE TREATMENT. SO THERE'S NEGATIVE BRAD. >> THANK YOU FOR YOUR COMMENTS.& WE HAD A SIMILAR DISCUSSION INTERNALLY AND THOUGHT WE WOULD CHANGE THE NAME SO NOT ONLY FOCUS ON OUR WARENESS, THE SECOND TIME, WE'RE KEEPING THE NAME BUT INCLUDED LANGUAGE IN ONE OF THE SLIDES EARLIER ABOUT WE LEAVE IT UP TO THE PEOPLE SUBMITTING ENTRIES WHAT THEY WANT TO FOCUS THE MESSAGE ON AS LONG AS IT'S LOOKING AT THE RARE DISEASE COMMUNITY COLLECTIVELY SO IT COULD BE ABOUT A CHALLENGE THAT OTHERS ARE FACING NOT ONLY SPECIFIC FOR THEIR DISEASE, IT COULD BE EVEN POTENTIAL SOLUTIONS THAT THEY HAVE IN MIND, SO DOESN'T HAVE TO ONLY BE ABOUT AWARENESS OR SOME OF THE RARE DISEASE STATS FLOATING OUT THERE ALL THE TIME. THEY CAN BE CREATIVE BUT WE DON'T WANT TO CONSTRAIN IT TO ONE-SIDED MESSAGE AND NOT BROADEN TO MORE CREATIVE IDEAS. >> IT OCCURS TO ME, WHAT BRAD AND ALICE SAID, IT'S TRUE. AND SO WE KIND OF VIEW AWARENESS AS A LITTLE BIT LIKE PUBLISHING A PAPER. SO WHAT? THAT DOESN'T HELP ANYBODY. SO AWARENESS IS GREAT BUT THEN SO WHAT? THE REASON ACTUALLY WE GOT INTO THIS, WE ACTUALLY BACKED INTO IT, FROM DISCUSSIONS WITH POLICYMAKERS DOWNTOWN, SOME OF WHICH REALLY SURPRISED ME, AND OUR COLLEAGUES AT THE NIH WHO MUCH TO OUR SURPRISE SAID, YOU KNOW, RARE DISEASES, YOU KNOW, IT'S JUST A NICHE. YOU KNOW, WE WERE JUST -- WE HAD SOME POLICYMAKERS DOWNTOWN, WE NEVER HEAR ABOUT THIS. UNQUOTE. I JUST ABOUT FELL OUT OF MY CHAIR WHEN I HEARD THIS. I'M IN THE CHOIR TOO, RIGHT? WE'RE CONSTANTLY TALKING ABOUT THIS. BUT IT'S -- IT CLEARLY HAS NOT REACHED -- IN THIS CASE WE WERE TALKING ABOUT THIS DISCUSSION, THIS PARTICULAR DISCUSSION I WAS HAVING, WHY THE ORDR BUDGET IS $24 MILLION A YEAR, WE GOT 7,000 DISEASES, IF YOU DO THE DIVISION IT DOESN'T COME OUT TOO WELL. THE ANSWER WAS THIS JUST ISN'T THOUGHT OF AS A PUBLIC HEALTH PROBLEM. WE GOT ALZHEIMER'S TO DEAL WITH. WE GOT OPIOIDS. THIS IS A NICHE PROBLEM BUT THERE'S A LOT WORKING ON THIS SO WE DON'T SEE THE PROBLEM. SOME COLLEAGUES, I LOVE MY COLLEAGUES AT NIH, BUT THEY WILL SOMETIMES SAY THE SAY THING. IT MADE ME APPRECIATE THE ECHO CHAMBER WE LIVE IN REALLY IS AN ECHO CHAMBER BUT IT'S WHAT YOU SAID, WE HAVE GET OUT OF THE ECHO CHAMBER. THAT'S SOMETHING WE'VE GOT TO THINK ABOUT. WE HAVE NOT DONE THAT. WE PATTED OURSELVES ON THE BACK, RARE DISEASE DAY, OH, YEAH, WE'RE NOW AWARE OF EACH OTHER MORE THAN BEFORE. GREAT. BUT A PRO-ACTIVE PLAN TO BEGIN WITH THE END IN MIND AND WORK BACKWARDS, THE END IS WHAT YOU GUYS ARE TALKING ABOUT, THIS IS SOMETHING WE'VE GOT TO THINK ABOUT. >> REINFORCE THAT, IT WAS BECAUSE PEOPLE GOT OUT OF THAT ECHO CHAMBER IN 1983 THAT WE GOT THE ORPHAN DRUG ACT IN 1983. >> YEAH, YEAH. >> BECAUSE THEY KEPT PRESSING THAT AND WENT ON TELEVISION WITH THE QUINCY SHOW AND THEY GOT TO THE PUBLIC AND THE PUBLIC BECAME AWARE, AND NOW LAST YEAR, 2018, MORE THAN HALF THE DRUGS THAT THE FDA APPROVED WERE FOR RARE DISEASES. SO I THINK THAT'S THE BOTTOM LINE. >> THE OTHER THING THAT WE'VE BEEN TOLD IS THE KNOCK-ON PROBLEM, THAT THERE'S NOT AN APPRECIATION HOW MUCH DISEASES COST THE AMERICAN ECONOMY IN TERMS OF DIRECT HEALTH CARE COSTS AND INDIRECT LOSS OF PRODUCTIVITY OF THE PEOPLE THEMSELVES AND THE FAMILIES. AND SO YOU HAVE GOT TO QUANTIFY THAT AS WELL. AND THAT'S THE ONLY WAY TO MAKE HEADWAY HERE. THEN WE WORK OUR WAY BACKWARDS, GEEZ, PEOPLE DON'T HAVE AN IDEA WHAT THESE THINGS ARE. SO WE'VE GOT TO START SOMEWHERE AND WORK FORWARD. LIKE YOU, I THOUGHT THIS PROBLEM WAS SOLVED. BUT IT WAS A LITTLE BIT, TO ME, LIKE GOING TO THE IOM MEETING ABOUT DRUG DEVELOPMENT. I THOUGHT, EVERYBODY KNOWS HOW DRUG DEVELOPMENT WORKS. AND THEN I REALIZED -- >> NOT SO MUCH. >> NOT SO MUCH. IT'S REALLY INTERESTING. YOUR POINT, WE'RE GOING TO DO THAT WITH REGARD TO THIS. >> BRAD, YOU'RE NOT A DOWNER BECAUS WE ACTUALLY HAD THIS DEBATE IN OUR FOUNDATION ABOUT TAKING AWARENESS OUT OF OUR MISSION. WHAT DOES AWARENESS GET YOU? SO WHAT? BUT I THINK THAT WE NEED TO GET THESE NUMBERS IN THE NEWS. AND BECAUSE THAT'S WHERE THE FUNDING -- THAT'S WHERE PEOPLE START THINKING ABOUT FUNDING. I ALSO THINK WE NEED TO GET REALLY -- SOME REALLY GOOD EXAMPLES OF WHERE RESEARCH AND DEVELOPMENT OF A DRUG FOR A RARE DISEASE LED TO A TREATMENT FOR COMMON DISEASES. AND AS WE'VE SAID EARLIER, AUTISM IS NOT -- AUTISM AND CANCER ARE NOT TWO DIFFERENT DISEASES. THEY ARE BOTH BIG WORDS FOR LOTS AND LOTS AND LOTS OF -- YOU KNOW. PHALEN PHELAN MCDERMID IS AUTISM, FRAGILE X IS AUTISM. WE NEED TO LEVERAGE TO SAY THERE'S TEN PEOPLE IN THIS ROOM AND SOMEBODY'S GOT A DISEASE. AND IT'S COSTING THE AMERICAN -- SOMEBODY'S GOT TO DO THE ANALYSIS. SO MANY YEARS AGO, DID THE ANALYSIS FOR AUTISM, FOR A FAMILY WITH ONE CHILD WITH AUTISM IT WILL COST X MILLION DOLLARS TO RAISE THAT CHILD. YOU HAVE TO PUT DOLLAR SIGNS ON THESE THINGS. IT DOESN'T SOUND SO CRAZY THE DRUG COST MILLIONS OF DOLLARS. THAT DRUG ISN'T FOR THREE KIDS. THAT DRUG IS GOING TO BE FOR 3,000 KIDS IN FIVE YEARS AND 3 MILLION KIDS IN TEN YEARS. AND I THINK THIS IS JUST ONE STEP. IT'S A $5,000 STEP FOR GOD'S SAKE, I DON'T THINK ANYBODY IS ARGUING THAT. BUT I THINK IT'S WHAT YOU DO WITH IT. ANNOUNCING THE WINNER ON RARE DISEASE DAY SOUNDS GREAT BUT I THINK TO RON'S POINT, IT MIGHT BE BETTER TO LAUNCH IT OR SKIP A YEAR AND LAUNCH IT SOONER AND HAVE -- BUT, YOU KNOW, MAYBE I'M NAIVE TO THINK CELEBRITIES AND ATHLETES CAN GET INVOLVED IN THIS. >> AT THIS POINT, IT'S BRINGING IT HOME. I BELIEVE IT NEEDS TO BE EXPANDED TO THE EXTENT THAT WE CAN LEARN FROM RARE DISEASES HOW TO SOLVE PRECISION AND PERSONALIZED MEDICINE. IT MAY BE CLEAR TO EVERYONE BUT LET ME EXPLAINMENT NUMBER ONE, THE AWARENESS LED TO REALIZATION NO ONE IS GOING TO TAKE CARE OF THAT. IT'S RARE. NO ONE CARES WHICH DROVE THE INITIATIVE, CRITICAL FOR APPLYING TO OTHER AREAS. ONE OF THE THINGS WE NEED TO REALIZE, WE'RE ALL RARE. PHENOTYPE IS LINKED TO GENOTYPE, IT'S A MATTER OF FACT. IN A SENSE, RARE IS ALSO INDIVIDUAL. AND SUDDENLY THAT'S WHERE PERSONALIZED AND PRECISION MEDICINE GOES, THAT'S WHAT WE AIM FOR. IT'S PUBLIC HEALTH PRIORITY. I THINK THAT'S THE OPPORTUNITY TO LINK RARE DISEASES AND EDUCATION ABOUT IT AND THE APPROACH IN TERMS OF INTERRUPTION, A WAY TO GET THE MONEY FROM THE PUBLIC AS WELL AS PRIVATE AND MAKE IT A CONSORT EFFORT. >> WHAT I'VE SEEN FIRST HAND IN THE RARE DISEASE COMMUNITY PEOPLE FEEL MORAL OBLIGATION TO CONTRIBUTE TO RESEARCH AS MUCH AS POSSIBLE BECAUSE THERE'S A NEIGHBOR DOWN THE STREET, YOU CAN HAVE BREAST CANCER AND NOT BE IN A CLINICAL TRIAL BECAUSE THE LADY DOWN THE STREET OR TWO BLOCKS OVER CAN DO IT. WHEN YOUR CHILD IS ONE OF A THOUSAND KIDS IN THE WORLD, YOU FEEL LIKE YOU NEED TO DO IT. I JUST DROVE TO NEW YORK FIVE TIMES IN FIVE WEEKS BECAUSE I FELT A MORAL OBLIGATION TO GET MY DAUGHTER IN A TEN-PERSON STUDY. THAT'S WHY THINGS HAPPEN FASTER IN RARE DISEASE. AND WE'RE A GREAT MODEL BUT UNLESS I'M MAKING THIS UP IN MY HEAD AREN'T THERE EXAMPLES OF RARE TREATMENTS READING -- LEADING TO COMMON TREATMENTS? >> A VERY GOOD DISCUSSION. WE DO HAVE -- ALL GOOD THINGS END. SO WITH NO ADDITIONAL DISCUSSION ON COULD WE HAVE A MOTION TO APPROVE THE CONCEPT? SO MOVED. >> SECOND? ALL IN FAVOR? >> AYE. ANY NOs? ANY ABSTENTIONS? WITH THAT THE CONCEPT IS APPROVED. NEXT UP IS DAN TAGLE. >> THIS ONE SHOULD BE SIMPLER. THAT'S WHAT I THOUGHT THE LAST ONE. >> LET'S HOPE SO. SO GOOD AFTERNOON, I'M GOING TO TALK ABOUT CONCEPT CLEARANCE FOR MICROPHYSIOLOGICAL SYSTEMS, AS YOU HEARD FROM CHRIS THIS MORNING TISSUE CHIP DATA BASE CENTER. BACKGROUND, WE'RE ALL ABOUT THE 3-Ds OF NCATS. IN 2012 TO 2017 DEVELOPED TISSUE CHIPS PROGRAM, PRIMARILY ON DEVELOPING MODELS FOR SAFETY. IN 2017 TO 2021 RENEWED THE PROGRAM, NOW FOCUSED ON DEVELOPING DISEASE MODELS PRIMARILY FOR EFFICACY TESTING, THE SECOND D WAS DONE PRIMARILY THROUGH DEVELOPMENT AND SUPPORT OF INDEPENDENT TESTING CENTERS, ONE AT M.I.T., ONE AT TEXAS A & M, DISSEMINATION PART OF TECHNOLOGY THROUGH THE MICROPHYSIOLOGICAL SYSTEMS DATABASE CENTER AT UNIVERSITY OF PITTSBURGH. SO THE ROLE OF THIS CONCEPT CLEARANCE IS TO ASK FOR YOUR APPROVAL TO REISSUE FUNDING OPPORTUNITY ANNOUNCEMENT THAT WILL ALLOW THE CONTINUED SUPPORT OF DATABASE CENTER, AS I MENTIONED HOUSED AT THE UNIVERSITY OF PITTSBURGH DRUG DISCOVERY CENTER. RIGHT NOW THIS IS THE ONLY DATABASE THAT HOUSES DATA, GENERATED FROM TISSUE CHIPS. AND IS BEING USED BY DEVELOPERS AND OTHER STAKEHOLDERS INCLUDING PHARMA. THIS IS LIKE WHAT THE DATABASE LOOKS LIKE. IT ESSENTIALLY TAKES TISSUE CHIP DATA AND INCORPORATE THE CLINICAL AND PRE-CLINICAL DATA AND PROPRIETARY DATASETS, FDA AND CHEMICAL STRUCTURES AND DRUG DATABASES, ALSO DEVELOP TOOLS THAT WILL ALLOW ASSESSMENT OF SAFETY AND EFFICACY, REPRODUCIBILITY AND DEVELOP COMPUTATIONAL MODELS FOR PK/PD STUDIES. JUST TO GIVE AN IDEA IN TERMS OF WHAT'S CURRENTLY IN THE DATABASE, WE HAVE ABOUT 58 MODELS THAT HAVE ALREADY BEEN DEVELOPED, THAT COVERS ABOUT 11 ORGAN SYSTEMS. FROM THE KIDNEY, LIVER, HEART, SKIN, MUSCLE, BONE, MANY OTHER ORGANS, AND IT CAME FROM RIGHT NOW AT LEAST 14 CENTERS. THIS DATA CAME FROM 171 STUDIES, 133,000 DATA POINTS, A LOT OF IMAGES, AND JUST TO GIVE A SENSE IN TERMS OF THE LEVEL OF ACCESS, THERE'S A NUMBER OF Q.C. POINTS BEFORE IT BECOMES PUBLIC ACCESS BUT ESSENTIALLY AT THE END OF THE DAY ALL THE DATA IS BEING GENERATED WILL BE MADE PUBLICLY AVAILABLE. IN TERMS OF USAGE, THIS IS JUST OVER -- A LITTLE OVER A YEAR PERIOD THAT SHOWS INCREASED USE OF DATABASE, AS MORE DATA IS BEING DEPOSITED, BY THE TESTING CENTERS. AND BY THE TISSUE CHIP DEVELOPERS. SO ON THE AVERAGE, NEW USERS EACH MONDAY LOG IN AND LOOK AT DATA AND DOWNLOAD THE DATA, EACH MONTH. THIS IS A FORMAT THAT WE ARE ASKED FOR OUR CONCEPT CLEARANCE. WHAT WE HOPE TO ACCOMPLISH WOULD BE TO DISSEMINATE -- CONTINUE TO DISSEMINATE TISSUE CHIP DATA, DEMONSTRATE REPRODUCE BUILD OF TISSUE CHIP DATA FOR PREDICTIVE SAFETY AND EFFICACY ASSESSMENT, POTENTIAL IMPACT FOR DEMONSTRATING AND DISSEMINATING TISSUE CHIP DATA TO THE COMMUNITY AND WHAT IS DIFFERENT ABOUT THIS PARTICULAR PROPOSAL TO RENEW IS THAT AT THE END OF THE TWO YEARS WHAT I PROPOSE IS TO HAVE THE DATA BASE BE SELF SUSTAINING. THIS IS SOMETHING THAT WE HAVE DONE FOR TESTING CENTERS, PREVIOUS FUNDING, AND THEY HAVE NOW SPUN OFF INTO A CRO, CRO-LIKE BUSINESS MODEL. AND WE'RE HOPING THIS IS ALSO SOMETHING THAT WE CAN DO FOR THE DATABASES. THIS IS ALONG THE LINES OF WHAT DR. LYNN MARKS MENTIONED IN TERMS OF CAN REVIEW BOARD, ASSESSING SUSTAINABILITY LONG TERM. IN TERMS OF EVALUATING THE CRITERIA FOR SUCCESS, OBVIOUSLY WE'RE LOOKING IN TERMS OF WIDESPREAD USE, ACCESS TO TISSUE CHIP DATA BY THE COMMUNITY. AND SUSTAINABLE NPS OR TISSUE DATA BASE CENTER, THAT PLAYS A CRITICAL ROLE ACTING AS CENTRAL REPOSITORY FOR TISSUE CHIP DATA, READILY ACCESSIBLE AND FACILITATES STANDARDIZATION, AND UTILIZATION OF THE DATASET. THE MAJOR OBSTACLE TO ADDRESS IS TRYING TO IDENTIFY WHAT IS THE BEST BUSINESS MODEL, TO SUSTAIN THE CENTRAL RESOURCE, THAT CAN HOUSE AND ANALYZE TISSUE CHIP DATA AND KEEP IT PUBLICLY AVAILABLE. IN TERMS OF ONGOING ACTIVITY, AND THIS RESEARCH AREA I MENTIONED WE HAVE DEVELOPED INDEPENDENT TESTING CENTERS, AND DATABASE CENTERS, AND THAT WAS STARTED IN 2016, AND I DID MENTION THAT THE TESTING CENTERS HAVE NOW CHANGED INTO MODEL SO THE SITE AT M.I.T. IS NOW JAVELIN BIOTECH AND TEXAS A & M IS CONSORTIUM MODEL. AND SO THE SUBJECT OF THIS CONCEPT CLEARANCE IS TO RENEW THE FUNDING FOR THE MPS DATABASE CENTER AT PITTSBURGH AND KEEP IT ALSO TO BE PUBLICLY AVAILABLE AND SELF SUSTAINING. IN TERMS OF CAN REVIEW BOARD PROJECT CRITERIA THIS IS COLLABORATIVE IN THE SENSE IT'S A PARTNERSHIP WITHIN NCATS, THE FDA, AND IQ MPS AFFILIATE MADE OF 22 PHARMACEUTICAL COMPANIES, THAT PROVIDED INPUT AND ALSO ARE THE BIGGEST STAKEHOLDERS IN THE USE OF TISSUE CHIP DATA. THEY ALSO PROVIDE INPUT IN TERMS OF WHAT THE BIOMARKERS, ASSAYS, ARE GOING TO BE USED IN TERMS OF VALIDATING THE COMPOUNDS AND SO THOSE ARE DATA THAT THEY WOULD LIKE TO SEE ALSO IN THE PUBLIC. IN TERMS OF MEASURABLE OUTCOMES WE WOULD PUT OUT THE SAFETY AND EFFICACY DATA FROM THE TISSUE CHIPS, ALSO ANALYTICAL TOOLS AND COMPUTATIONAL MODELS FOR UNDERSTANDING THE MECHANISMS OF THE DISEASE COMPOUND TOXICITY AND PREDICTING PK FOR A NUMBER OF CANDIDATE DRUGS. WE'LL HAVE BROAD AND SIGNIFICANT IMPACT IN THE SENSE AGGREGATE DATA SET WITH PRE-CLINICAL AND CLINICAL DATA WILL BE COMING FROM VARIOUS SOURCES, AS ALREADY MENTIONED, AND WILL HAVE ABILITY TO DO ASSESSMENT OF PROMISING THERAPEUTICS, RESULTING FROM THE TISSUE CHIP DATA. DISEASE RELEVANCE, DATABASE IS APPLICABLE TO WIDE RANGE OF HUMAN DISEASES AND CONDITIONS, AND AS I MENTIONED, THE FOCUS OF THIS CONCEPT CLEARANCE IS TO TRANSITION DATABASE CENTER INTO A SELF SUSTAINING ENTERPRISE. AND WITH THAT I'M OPEN TO QUESTIONS, OR ANY DISCUSSION. >> BEFORE YOU DO THAT, COULD YOU CLARIFY PEOPLE ARE WONDERING WHY IS CENTERS TRANSITIONING, THIS ONE ISN'T? >> TESTING CENTERS HAVE TO DEVELOP DATABASE, THERE'S A LAG WHEN THE DATABASE CAN BE -- WHICH I THINK CAN BE STANDING ON ITS OWN. >> DISCUSSANTS ARE LYNN AND ALAN. >> I'LL START. THANKS, DAN. I THINK IN THE CONTEXT OF THE CONCEPT CLEARANCE, I THINK IT MAKES SENSE TO CONTINUE WITH THIS. OBVIOUSLY THIS IS GOING TO BE A MAJOR POINT OF DATA REPOSITORY FOR ESTABLISHING THE CONCEPT, VALIDATION SETS, COMMUNICATION WITH THE BROADER COMMUNITY, KEY POINT OF ENGAGEMENT. I'M WONDERING AS I MOVE FORWARD, RELATING TO EARLIER DISCUSSION ABOUT DISSEMINATION, ARE THERE OTHER THINGS THAT COULD BE CAPTURED? AS GROUPS BEGIN TO UTILIZE THE TISSUE CHIPS AND INTEGRATE INTO PROGRAMS, THERE COULD BE USE CASES THAT REALLY HELP OTHER INVESTIGATORS -- HOW DO I IMPLEMENT THIS INTO MY DRUG DISCOVERY PROGRAM? WHAT HAS BEEN THE LEARNING? HOW CAN I USE THIS TO AUGMENT SAFETY PROFILING AND QUICKER WAY? INSTEAD OF JUST DATASETS, BUT UNDERSTANDING HOW TO PLUG IT IN AND REALLY THINK ABOUT TRANSFORMING THE DISCOVERY PROCESS, WITH THIS TECHNOLOGY? AND SO YOU'VE HAD EXAMPLES EARLIER, WITH THE INTRAMURAL PROGRAMS BEGINNING TO ADOPT THIS, THAT COULD BE A GREAT EXAMPLE. OTHERS WOULD BE WILLING TO SHARE AS THEY BEGIN TO ENGAGE WITH THIS TECHNOLOGY, THAT WOULD BE REALLY, REALLY HELPFUL TO TRY TO INSULATE A GROUND WORK IN THIS PLATFORM, THIS DATA PLATFORM, IF POSSIBLE FOR THOSE WILLING TO SHARE. AND RELATED TO THAT, AS YOU'VE BEEN WORKING WITH A NUMBER OF PHARMA COMPANIES, A PLACE TO START BUT ALSO IS A LOT OF DIVERSITY IN THE COMMUNITY. WHAT HAS BEEN YOUR SENSE OF HOW THEY HAVE UP ENGAGED? SOME PROVIDED COMPOUNDS? OTHERS BROUGHT US INTO THE PROGRAM, OTHERS MAY BE A WAIT AND SEE. WHAT HAVE YOU SEEN IN THE COMMUNITY? THAT WOULD BE A REAL BELLWETHER FOR HOW THIS ACTUALLY TAKES OFF AND THEIR VOICE WILL BE VERY IMPORTANT. >> YES, THANK YOU FOR YOUR COMMENTS. IN TERMS OF END USERS AND BEING ABLE TO ACCESS DATASETS, THERE ARE A NUMBER OF, AS YOU SAW FROM THE NUMBER OF END USERS, LOGGING IN AND DOWNLOADING DATA, SO THERE ARE DEFINITELY INTERESTED IN WHAT'S BEING TESTED, WHAT PLATFORMS ARE AVAILABLE FOR WHAT DISEASE MODELS. AND WHAT COMPOUNDS WORK AND WHAT ASSAYS WORK BEST FOR DIFFERENT PLATFORMS. SO IT'S REALLY MORE TO THE POINT OF CONTEXT OF USE. EACH ONE OF THESE MODEL SYSTEMS ARE SPECIFIC FOR PARTICULAR CONTEXT OF USE. OUR INTERACTIONS WITH PHARMA HAS BEEN PRODUCTIVE, AS WE HAVE SET UP IN A PROGRAM FROM THE BEGINNING, INTERACTION WITH FDA,REGULATORS, PHARMACEUTICAL COMPANIES. WHERE WE'RE AT WITH PHARMA, I'M ACTUALLY HAVING A PHONE CONFERENCE NEXT WEEK WITH IQ FINALIZE AND CONTINUE THE DISCUSSION OF PUTTING IN DATA SETS THAT PHARMA HAD GENERATED INTO THE DATABASE TO FURTHER POWER UP THIS PARTICULAR DATABASE CENTER. SO PHARMA IS WILLING TO PUT IN SOME OF THE DATA THAT THEY HAVE GENERATED, ESSENTIALLY AS PART OF THE I.Q. CONSORTIUM, WORKING GROUP AFFILIATE, AND THEY HAVE LOOKED UPON THIS AS A RESOURCE THAT ESSENTIALLY SERVED LIKE I SAID AS A CLEARINGHOUSE FOR A LOT OF THESE DATASETS. >> DAN, I'M A HUGE FAN OF THIS WORK THAT YOU'VE DONE, AND THE TEAM IN GENERAL IN TERMS OF TRYING TO TAKE US TO THE NEXT STEP WHERE WE JUST DON'T USE ANIMALS TO TRY TO PREDICT WHAT'S HAPPENING IN HUMANS. IT'S UNRELIABLE. NOT VERY PREDICTABLE. I MEAN, IT'S JUST NOT -- WE GOT TO DO THIS, RIGHT? THE QUESTION I HAVE, YOU ALREADY ANSWERED PART OF IT, HOW DO WE KEEP MOVING THE DATA IN, HOW DO WE MAKE SURE WE DISSEMINATE, AS YOU NOTED WHO IS GOING TO PAY FOR IT MOVING FORWARD. SO SORT OF JUST TRYING TO BE PRAGMATIC ABOUT MY LINE OF THINKING IS WHAT IF WE SAID NO? WOULD THAT ACTUALLY ENABLE YOU TO GET QUICKER FASTER OWNERSHIP TO SUSTAIN IT IN MOVING FORWARD RATHER THAN TAKING ANOTHER TWO YEARS TO FIND THAT OUT? BECAUSE YOU'VE GOT THE INDUSTRY, YOU'VE GOT THE CONSORTED YUM THAT YOU TALKED ABOUT. WHY CAN'T THEY GET TOGETHER AND MAKE SOME DECISIONS NOW UNDER THE THREAT OF NOT BEING ABLE TO CONTINUE IT? IF IT'S SHOWING THE KIND OF VALUE THAT I PERSONALLY BELIEVE IT'S GOING TO HAVE. >> YEAH, THAT IS A GOOD POINT. EVEN THOUGH THERE'S WIDESPREAD INTEREST AMONGST PHARMA, MEETING WITH THEM IN BOSTON A COUPLE WEEKS AGO, I THINK THE REALITY IS THERE, MANY LEGAL LOOPHOLES TO WORK THROUGH TO BE ABLE TO SHARE THE DATA AND TALKING WITH THEM THEY DO NEED THE TIME TO WORK THAT THROUGH. AND THIS IS SOMETHING THAT WE'RE -- WITH A CONFERENCE CALL NEXT WEEK HOPING TO FACILITATE SOME OF THOSE INTERACTIONS. YES, WHILE THERE IS INTEREST, I THINK THERE NEEDS ALSO TO BE ADDITIONAL INVESTMENT BY NCATS TO KEEP THINGS MOVING, PHARMA IS NOT THE ONLY ONE WHO IS GOING TO BE PUTTING IN DATA THAT TISSUE CHIP DEVELOPERS THEMSELVES, TESTING CENTERS ARE ALSO GOING TO START PUTTING IN DATA, NOT ONLY FOR THE SAFETY MODELS BUT ALSO FOR THE DISEASE MODELS. WE ACTUALLY ARE IN CONVERSATION WITH THE MEMBERS OF THE FDA WHO HAVE GENERATED TISSUE CHIP DATA, ALSO WILLING TO PUT IN SOME OF THE DATASETS. THE PERIOD OF TWO YEARS WOULD BE AN IDEAL TIME TO CONTINUE TO SUSTAIN THIS ACTIVITY. >> CAN YOU ELUCIDATE A LITTLE BIT MORE HOW THIS INTERSECTS WITH OTHER DATA BASES LIKE GSRS, GLOBAL SUBSTANCE REGISTRY, THE FDA, WANTS TO MAKE AN OPEN PLATFORM, WITH OPEN TECHNOLOGY, WHY, BECAUSE OF SUCH SIGNIFICANT IMPACT THAT IT STAYS OPEN, COMES OPEN, DOESN'T MEAN IT WOULDN'T HAVE PROPRIETARY SECTOR. THEIR INNOVATORS HAVE A GRACE PERIOD UNTIL A PRODUCT BECOMES APPROVED, AND THERE BY IT BECOMES PUBLIC INFORMATION. SO THE -- I UNDERSTAND YOU NEED CRITICAL MASS TO MAKE IT SWEET, THIS IS GOING TO BE A FEE FOR SERVICE, HOW THIS INTERSECTS WITH OTHER DATA RESOURCES IN THE DATA BASE, PARTICULARLY GSRS, SOMETHING WE'RE INTERESTED IN, AND HOW DO YOU KEEP IT OPEN ACCESS OR HOW DO YOU REGULATE ACCESS? >> YEAH, SO THAT'S A GOOD POINT, FRANK. IN TERMS OF INTERACTIONS WITH GSRS, WE ARE -- THAT'S SOMETHING THAT'S ALREADY HAPPENING, WE ALSO HAVE RESOURCES OR INCORPORATION OF OPEN DATA, FDA OPEN DATA SET, SO THAT'S ALSO PART OF IT, WHICH IS PRETTY MUCH ADVERSE EVENTS. AND THE MODEL OF THIS DATABASE IS VERY MUCH LIKE GSRS IN TERMS OF TIERED ACCESS, THERE'S A TIME WHEN THE DATA, LIKE I SAID, IS UNDERGOING Q.C. AND REMAINS PRIVATE, BUT WE HAVE A PERIOD OF ONE YEAR TO MAKE THAT HAPPEN. AND THEN IT GOES PUBLIC. IN TERMS OF WHAT IS THE BEST MODEL TO MAKE ITSELF SUSTAINABLE IS SOMETHING WE'LL HAVE TO POST TO THE APPLICANT TO SEE WHAT THEY CAN COME UP WITH AND OF COURSE HAVE PEER REVIEW EVALUATE THAT BUSINESS MODEL. AND FIND OUT IF THAT IS SOMETHING THAT WOULD ALLOW IT TO BE NOT ONLY SUSTAINABLE AND AS WELL AS MAINTAIN THE PUBLIC USE OF THIS DATABASE. >> CAN YOU SAY SOMETHING ABOUT -- ARE YOU COLLECTING CORRELATIVE DATA OR TRYING TO MAKE CORRELATIONS WITH ANIMALS IN THE CHIP OR HUMAN SAFETY ISSUES THAT OCCURRED IN THE CHIPS, OR CONNECTING THE DOTS? OR IS THIS ALL ABOUT INCREASING GETTING SO MUCH INFORMATION ON THE TISSUE CHIPS, WILL BE USEFUL IN AND OF THEMSELVES? >> THE MAIN ACTIVITY IS BASED ON HUMAN CELLS. HUMAN CELLS AND TISSUES. THERE ARE SOME ACTIVITIES CORRELATEIVE DATA SETS, PRIMARILY COMING IN FROM -- INTEREST FROM PHARMA, THEY HAVE FUNDED THOSE KINDS OF ACTIVITIES BUT THAT'S NOT SOMETHING NCATS SUPPORTED IN TERMS OF FUNDING BUT PRIMARILY COMING FROM THE PRIVATE SECTOR SO THERE ARE SPECIFIC ANIMAL SPECIES THEY WANT TO SEE ON CHIPS, AND THEY HAVE COME FORWARD AND FUNDED THOSE KIND OF ACTIVITIES AND TRYING MAKE CORRELATES WITHIN HUMAN AND CHIP VERSUS ANIMAL AND CHIP DATASETS. >> MY QUESTION MAY NOT HAVE BEEN CLEAR. I WAS ASKING ABOUT ACTUAL ANIMALS, IF YOU HAVE LIVER CELLS ON A CHIP, AND THEN LOOK FOR LIVER TOXICITY, HAVE CORRELATIVE DATA OF LIVER TOXICITY IN AN ANIMAL OR OF A DRUG IN A HUMAN. >> YEAH, SO THAT'S WHAT I MEAN. A LOT OF THE DATA SETS IN TERMS OF DRUG DEVELOPMENT HAVE COME IN FROM IN VIVO ANIMAL WORK, WHICH HAVE LED TO USE IN HUMAN TRIALS. BUT ALMOST ALWAYS THOSE DRUGS HAVE BEEN WITHDRAWN, AND SO THE DATA SET THAT WE'RE LOOKING AT ARE PRETTY MUCH LOOKING AT THE SAME COMPOUNDS THAT HAVE GONE THROUGH SAFETY STUDIES IN ANIMALS BUT HAVE FAILED IN HUMAN AND DATA SHOWS THE TISSUE CHIPS ACTUALLY CONFIRM TOXICITY IN HUMANS AND WOULD HELP PREDICT TOXICITY IF USED IN PRE-CLINICAL SAFETY ASSESSMENT. >> JUST GO BACK TO SLIDE 4. I THINK IT ANSWERS MIKE'S QUESTION BECAUSE IT'S -- THE ONE WITH THE DIAGRAM. RIGHT THERE. YEP. YOU SEE WHAT IT'S DOING IS PULLING IN ALL THOSE THINGS, AND -- BUT SOME OF THAT, MY SENSE IS SOME OF THAT OTHER -- THOSE OTHER DATA TYPES, ONE OF THE THINGS THAT THE DATABASE IS GOING TO FOCUS ON INCREASELY NOW THAT THEY HAVE THE STUFF IN THE MIDDLE, ALL THAT OTHER STUFF, YEAH, WHICH IS REALLY WHERE THE -- THAT'S WHERE THE RUBBER HITS THE ROAD, YEAH. OKAY >> ONE MORE QUICK QUESTION, DAN. YOU TALKED ABOUT HOW THE PHARMA PARTNERS ARE CONTRIBUTING DATA. AS THERE BEEN AN INSTANCE WHICH THEY ARE ALSO PROVIDING FUNDING FOR THIS PROGRAM? >> THEY HAVE NOT YET CONTRIBUTED DATA. THEY ARE STILL IN DISCUSSIONS, HOW TO GO ABOUT DOING THAT ACROSS PHARMA. BUT THERE'S DISCUSSION TO DO SO. THEY HAVE NOT CONTRIBUTED FINANCIALLY TO THIS ACTIVITY, ALTHOUGH LIKE THE FDA THEY HAVE CORRECTED EXPERTISE AND GUIDANCE IN TERMS OF HOW TO STRUCTURE THE DATA SO END USERS, REGULATORY AGENCIES AND PHARMA, IS ABLE TO FULLY UTILIZE IT. AGAIN, KEEPING THE END USERS IN MIND FROM THE VERY BEGINNING. >> DO YOU HAVE A COMMENT? ALL RIGHT. ANY ADDITIONAL DISCUSSION ON CONCEPT NUMBER 2 FOR THE DAY? THANK YOU VERY MUCH FOR THE DISCUSSION. >> THANK YOU. >> COULD WE HAVE A MOTION TO APPROVE THE CONCEPT PLEASE? >> SO MOVED. >> SECOND? >> SECOND. >> ALL IN FAVOR? >> AYE. >> ANY OPPOSED? ANY ABSTENTIONS? >> (INAUDIBLE). >> WITH THAT THE CONCEPT IS APPROVED. THANK YOU VERY MUCH. >> OKAY. SO WE ARE 24 MINUTES BEHIND BUT THAT'S OKAY BECAUSE WE HAVE 30 MINUTES OF OPEN DISCUSSION AT THE END, WHICH I THINK WE JUST HAD. SO WE HAVE 6 MINUTES FOR THE QUAKER MEETING PORTION OF OUR PROGRAM, THAT IS THINGS ON YOUR MIND. SO DO THINK ABOUT THOSE THINGS, HOPEFULLY WE'LL HAVE SOME TIME AT THE END. AS IN EVERYTHING IN OUR LIVES, INFORMATICS IS BECOMING EVEN MORE IMPORTANT THAN WE THOUGHT IT WAS THE YEAR BEFORE. AND KEN IS OUR DIRECTOR OF INFORMATICS ON THE CLINICAL SIDE, HE'S OFFICIALLY IN THE DCI PART OF THE ORGANIZATION, IN ADDITION TO BEING AN INFORMATICS WHISPERER, YOU KNOW, HE USES ALL OF THAT STRANGE TRIBAL VERNACULAR THAT THOSE INFORMATICS PEOPLE DO AND HE'S GOING TO SHOW US LOTS OF PICTURES WHICH HAVE WATER TANKS ON THEM BECAUSE THEY ALWAYS SHOW THOSE WITH ARROWS, HE'S A PSYCHIATRIST BY TRAINING, WHICH EXCEEDINGLY USEFUL IN GETTING PIECES TO WORK TOGETHER. HYPNOSIS HAS BEEN USED SEVERAL TIMES NAP IN THE EFFORTS. IT'S PRETTY EXCITING STUFF, WHAT'S GOING ON. SO, KEN, TELL US WHAT YOU'RE UP TO >> THANK YOU. MY NAME IS KEN GERSING, WORKING THREE THREE-PLUS YEARS NOW. CHRIS CAME UP WITH THE IDEA OF DOING A SERIES OF DISCUSSIONS WITH THE COUNCIL OVER THE NEXT FEW SESSIONS ON WHAT'S HAPPENING WITH INFORMATICS WITHIN NCATS BECAUSE THERE'S A LOT OF EXCITING THINGS GOING ON, INFORMATICS IS SOMETIMES SOMEWHAT LIKE PLUMBING. IT SHOULD BE -- YOU SHOULDN'T HAVE TO KNOW ABOUT IT. HOPEFULLY YOU DON'T HAVE TO KNOW ABOUT IT. BUT IT ACTUALLY MOVES A LOT OF THINGS. SO TODAY WE'LL HAVE TALKS ABOUT MACHINE LEARNING, ARTIFICIAL INTELLIGENCE, AND THEN AFTER THAT WE'RE GOING TO ACTUALLY HAVE SOME FOLKS TALK ABOUT WHAT NCATS IS DOING IN THE CLOUD INFRASTRUCTURE THAT'S SUPPORTING A LOT OF THE EFFORTS THAT YOU'VE HEARD ABOUT TODAY. WE'RE GOING TO TALK ABOUT A DATA LIFE CYCLE, TECHNOLOGY CALLED FHIR, DATA SHARING, AND NCATS CLOUD IN HOW WE'RE USING IT WITHIN THE CTSA. SO, A LOT OF PEOPLE SAID IF WE CAN'T GET DATA TO WORK TOGETHER WE CAN'T DO TRANSLATIONAL SCIENCE. I'M GOING TO BREAK UP THE LIFESTYLE, LIFE CYCLE OF DATA INTO THREE PLACES, COLLECT, USE AND SHARE DATA. BEFORE I GET TO DISCUSSING THIS, I NEED TO TALK TO YOU ABOUT DATA STANDARDS, AND THIS SOUNDS SOMEWHAT ARCANE BUT IS REALLY IMPORTANT, IN THE WORLD OF EMRs AND BILLING THE OFFICE OF NATIONAL COORDINATOR AND CMS MANDATED PEOPLE USE A MESSAGING SYSTEM BY A STANDARDS ORGANIZATION CALLED HL7, HEALTH LEVEL 7 IS WHAT IT STANDS FOR. IN THE REGULATORY WORLD, YOU ALL PROBABLY KNOW THAT THE FDA MANDATES THAT THINGS HAVE TO BE SUBMITTED IN A FORMAT, SDTM, BY A GROUP CALLED CDISC, ALSO STANDARDS. THE NIH RIGHT IN THE MIDDLE, THERE IS A QUESTION MARK. WE HAVE NO STANDARDS. THIS HAS CAUSED ENORMOUS PROBLEM. WHAT WE ALLOWED IS PEOPLE TO CREATE THEIR OWN PROPRIETARY STANDARDS, THE DATA DOESN'T TALK TO EACH OTHER. YOU COLLECT MAIL AS AN M, I AS A 12, SOMEBODY AS 13, WE HAVE TO SPEND HOURS TRYING TO MAKE THESE THINGS MATCH. SOMETIMES WE THINK THEY MATCH AND THEY SEMANTICALLY BUT IT GOES ON. ON JULY 30 THIS YEAR THE NIH SAID THEY ENCOURAGE FHIR, AND PRONOUNCED FIRE, SPELLED F-H-I-R. FHIR IS QUITE AN AMAZING ANNOUNCEMENT BECAUSE WHAT THEY ARE SAYING IS THE FIRST TIME RESEARCH INFORMATION SHOULD USE A STANDARD, QUITE A CHANGE, A SEE CHANGE, IT WILL MAKE THE WORK WE DO OF DATA YANG LYNN EASIER IF WE KNOW WHAT THE DATA IS. TODAY I'M GOING TO TALK ABOUT FHIR AND WHY IT'S SIGNIFICANT. FHIR IS FROM HL7, FAST HEALTH CARE INTEROPERATIVE RESOURCES. FHIR WAS STARTED BY SOME INVESTIGATORS, ACTUALLY ED HAMMOND WORKS WITH US, IN OUR CTSA, GOING ON SINCE THE '70s. INTERESTINGLY ENOUGH, WHAT THEY REALLY SAID IS WE'VE GOT TO BE ABLE TO MOVE INFORMATION IN A ELECTRONIC RECORDS, CLINICAL WAYS, IN A STANDARD MESSAGING SET. LATER ON THEY DEVELOPED NOT ONLY DOES IT HAVE TO GO A CERTAIN WAY, TRAIN TRACKS, BUT WHAT'S IN THE CAR ON THE TRAIN TRACKS. AND SO THEY ACTUALLY, TO DATE MYSELF, THE METHODS THEY USED, A BARDA LIMITED FILE FORMAT. THINK BACK TO PUTTING PUNCH CARDS IN A COMPUTER, THIS WAS ONE GENERATION PAST THAT. THERE WAS A BAR, YOU COUNTED THE NUMBERS, ANOTHER BAR, COUNTED NUMBERS, PEOPLE WITH PhDs WOULD SAY THIS DIDN'T WORK BECAUSE THE A WAS IN POSITION 7. ACTUALLY FHIR -- I MEAN HL7, 2.0, DRIVES 90% OF ALL MESSAGES IN AMERICA. 1960s, 70s TECHNOLOGY. 1995 THEY SAID WE SHOULD UPDATE TO XML, NOBODY ADOPTED. WE WENT TWENTY YEARS, FIVE YEARS AGO GRAHAM GRIEVE CAME UP WITH FHIR, IT SPED LIKE FIRE USING TECHNOLOGY THAT'S EASY AND SIMPLE TO IMPLEMENT. I'LL COMPLAIN HOW AND WHY IT'S USED. I'VE GOT BUNNIES IN MY EXAMPLE, SO DID ANNE, WE'RE ALIGNED WITH THE RARE DISEASE GROUP. WHAT IS FHIR? THE METAPHOR, CHRIS SAID YOU CANNOT DO GEEKY STUFF. THIS IS MY KNOWLEDGE GEEKY VISION OF FHIR. IT'S A CONTAINER. YOU KNOW THOSE CONTAINERS, YOU SEE THEY ARE ON TRUCKS, THEY ARE ON BOATS. THEY ARE ON TRAINS. THOSE ARE CALLED INTERMODAL CONTAINERS. I CAN'T OVERSTATE THE SIGNIFICANCE OF THE WORLD DEFINING THE BOX THAT WE SEE METAL CONTAINERS, THE SAME SIZE, WE KNOW HOW THEY ARE GOING TO FIT AND TRAINS AND BOATS HAVE ALL BEEN MODIFIED TO TAKE THOSE. SO FHIR SAYS WE'RE GOING TO HAVE A CONTAINER. OKAY? AND THEN INSIDE -- WE'RE GOING TO PUT A WRAP AROUND THE CONTAINER, THE METADATA, THAT DESCRIBES WHAT'S IN THE CONTAINER. THEY ARE NOT GOING TO SAY WHAT YOU CAN PUT IN BUT IF YOU HAVE TO PUT IT IN THIS FORMAT SO ANOTHER COMPUTER COULD READ IT. I WANT TO PUT BICYCLES IN, YOU COULD PUT BUNNIES OR SOMETHING ELSE, BUT IT COULD ALL WORK, BE OKAY BECAUSE THE COMPUTER WOULD KNOW IT HAS THIS METADATA AROUND IT AND IT'S IN THE STANDARD CONTAINER AND WE WOULD BE ABLE TO MOVE THIS INFORMATION. SO, A LITTLE BIT MORE ON HOW THIS WORKS, KIND OF A SIMPLIFIED IMAGE. SO, THE WAY I SEE HOW FHIR IS MOVING INFORMATION, THINK ABOUT THE DATA BASE IN A HOUSE. THE HOUSE HAS AN ADDRESS. WE CALL THAT IN THE COMPUTER WORLD A URL. IF I GOT TO THE HOUSE, I COULDN'T GET IN THE HOUSE, UNLESS I HAD A KEY. IF I HAD THE KEY, WHICH WE CALL AN API, APPLICATION INTERFACE, PROGRAMMER INTERFACE, I COULD OPEN THE DOOR. WHAT CAME OUT WAS A CONTAINER THAT TOLD ME WHAT WAS IN IT, I KNEW WHAT SIZE IT WAS, THEN I COULD ACTUALLY TAKE THAT CONTAINER, USING A STANDARD LANGUAGE, THAT YOU MAY HAVE HEARD CALLED JAY-SON, WHICH IS NOT TO GET A LITTLE BIT OFF INTO THE GEEK LAND BUT THAT IS A STANDARD LANGUAGE THAT IS INTERNET BASED. THINK ABOUT I CAN STICK IT IN MY BROWSER, SEE IT FROM THERE T EASY TO DO. I COULD STICK IT ON A TRUCK OR TRAIN OR ON A BOAT. THIS THING IS GOOD. SO WHY AM I TELLING THE STORY AND HOW DOES IT AFFECT THE THINGS WE'RE TALKING ABOUT? IN THE CLINICAL WORLD WE HAVE DATA MODELS. YOU MAY HAVE HEARD OF THEM. OMOP, DATA RIGHT FROM THE EMR, AND DATA MODELS DON'T TALK TO EACH OTHER AND REPRESENTATIVE DIFFERENT CONSTITUENTS, POETIC LICENSE, PCORI IS REALLY KIND OF COMMUNITY DATA. SENTINEL IS -- THINK ABOUT HMO DATA. MOSTLY BILLING DATA. I2B2, ACADEMIC, OMOP IS INTERNATIONAL DATA STARTED BY J AND J. IF I WANTED TO GET INFORMATION FROM THESE CONSTITUENTS, ALL THESE NETWORKS, RIGHT NOW I CAN'T DO IT. AND SO WHAT WE'RE TRYING TO SAY IS IF WE COULD CONVINCE THESE FOLKS TO USE THIS STANDARD WHICH NOW THE NIH IS SUPPORTING AND CMS IS SUPPORTING, ONC IS SUPPORTING, THEN I ACTUALLY COULD USE THIS SAME TRANSPORT MECHANIC NICHE TO DO LOTS OF DIFFERENT THINGS. SO WE HAVE A PROJECT THAT WE'RE WORKING ON WITH OUR PARTNERS, CDC, FDA, NCI, ONC, CD2H WORKING& ON THIS PROJECT TOGETHER. WE'VE BEEN WORKING ON THIS FOR 18 MONTHS. AND EACH OF THE GROUPS WANTS TO GET SOMETHING DIFFERENT OUT OF THIS TRANSPORT, BUT WE'RE ALL USING INTERCHANGEABLE PARTS SO INSTEAD OF BUILDING AN NIH SYSTEM WE'RE BUILDING AN HHS SYSTEM THAT EVERYBODY CAN SHARE AND USE THE SAME BUILDING BLOCKS. SO, SURVEILLANCE DATA IS GOING TO -- ACTUALLY IDENTIFIED DATA, THAT'S WHAT THE CDC WILL GET. FDA WANTS SAFETY DATA. NIH WANTS RESEARCH DATA. IT ALL USES THE SAME LEGO SET. NOW THAT YOU HAVE SEEN MY CARTOONS, THIS IS ACTUALLY WHAT IT LOOKS LIKE, WHERE I GET TO PUT MY DATABASES WHICH MIKE CALLS THE BARREL. WE'VE GOT TO QUERY THE DATA, FOR THE HIGH GEEK FACTOR WE'VE GOT TO USE A STANDARD QUERY LANGUAGE CALLED CQL, DEVELOPED FOR MEANINGFUL USE, ALLOWS DATA USE, ONE TYPE OF QUERY LANGUAGE. WE'RE GOING TO STICK IT IN THE FHIR SERVER, THE FHIR SERVER IS REALLY REPRESENTING THE DATA IN A COMMON WAY, SO AGAIN IT'S A LINGUA FRANCA OF GETTING DATA. THEY ARE NOT GOING TO PULL THE DATA FROM THE COMMON DATA MODEL, THINK ABOUT THE THINGS I JUST SAID, OMOP, SENTINEL AND PCORnet, I USED A COMPANY, WE HAD A THOUSAND TABLES, EPIC HAS OVER TWO THOUSAND TABLES, SO ALL THOSE OTHER 980 TABLES, THEY ARE NOT AVAILABLE FOR RESEARCH. SO THE DATA IN EMR IS BAD, I WOULD NOT DEFEND IT. IT NEEDS CLEANING, BUT ONE OF THE REASONS IT'S LIMITED USE WE DON'T HAVE WHAT WE NEED, TEMPORAL DATA. I DON'T NEED TO KNOW JUST THAT YOU GOT A MEDICINE. I NEED TO KNOW WHEN YOU'RE IN ICU BEFORE OR AFTER YOU CRASHED, WHEN THE BLOOD PRESSURE CAME FROM THE DYNA MAP. I CAN GET THAT INFORMATION FROM FHIR. FHIR WAS -- THERE WAS A PROJECT CALLED THE ARGONAUTS, WHICH EXPANDED FHIR TO THE CLINICAL WORLD TO COVER THE HL7. A PROJECT CALLED DaVINCI, THE CMS GOT INVOLVED, NOW TRANSPORTING INFORMATION FOR BILLING WHICH IS REQUIRED THROUGH FHIR, BUT WE AS WE'RE ENDORSING FHIR THERE ARE A LOT OF FHIR RESOURCESES FOR MISSING, DEATHS INDEX OR SAE. WE'VE GOTTEN A SEAT AT THE BOARD OF THE FHIR GROUP, HL7 GROUP, WE HAVE A PERSON WHO WILL SAY THIS IS WHAT WE NEED TO EXPAND FHIR RESOURCES SO IF NIH IS GOING TO SAY YOU NEED TO USE IT, WE ACTUALLY HAVE SOMEONE WHO CAN HELP BUILD THAT FHIR. ONCE WE DO THAT, NOT SURPRISING FOR FOLKS WHO HAVE FER IMPLEMENTED EMRs, STEP BACK, REALLY NOT WELL OVER 97% OF ALL CTSAs USE EPIC. IT'S A MONOPOLY IN ESSENCE ACROSS THE CTSA BUT ONE EPIC IS ONE EPIC. THEY DON'T TALK TO EACH OTHER. IT'S CALLED PERSONALIZATION. WE'RE WORKING WITH NCI TO CREATE TERMINOLOGY SERVICES, THINK ABOUT THIS AS KIND OF NOT A PALACE, WHERE DATA GOES TO SAY WHAT SHOULD IT BE IF I WANT TO MAKE IT A STANDARD. ONCE WE DO THAT WE NEED TO AGGREGATE DATA IN A SIMP THE SPOT. IF I PUT OUT A QUERY, TEXAS, UNC, ALABAMA, WHOEVER, I NEED TO BRING IT ALL IN TO A SINGLE SPOT AND COMBINE IT AND EXPORT IT TO DIFFERENT FORMATS LIKE I SAID, NIH IS GOING TO WANT A DIFFERENT FORMAT, CDC, FDA. WE SHOULD HAVE A PROTOTYPE BY THE END OF THE CALENDAR YEAR. THAT'S WHAT WE'VE BEEN WORKING ON. THIS IS A PROJECT WITHIN THE CD2HN. I WANT TO TAKE A STEP BACK FOR A SECOND AND TALK ABOUT A LITTLE ABOUT FAIR. I ASSUME A LOT OF FOLKS HAVE HEARD, FINDABLE, ACCESSIBLE, INTEROPERABLE, REUSESSABLE. JUST BECAUSE YOU'VE GOT DATA DOESN'T MEAN YOU CAN USE THE DATA. IF YOU DON'T HAVE THE LICENSE TO USE IT OR IF THE CLINICIAN WON'T ALLOW YOU TO USE IT YOU'VE GOT NOWHERE. AND SO ONE OF THE THINGS I WANT TO TALK ABOUT IS REALLY WHAT I SAY IS HAVING FHIR WITHOUT -- IT'S JUST GOING SMOKE UNLESS IT'S FAIR DATA. IF YOU LOOK ON -- THIS IS WHAT FAIR STANDS FOR, THERE'S A RED ASTERISK, BY ALL THE AREAS WORKING HARD ON MAKING DATA THAT WE'VE BEEN ABLE TO FIND, USING FHIR, FINDSABLE, FAIR, USABLE. THERE ARE VERY FEW AREAS NOT FUNDED. ONE IS ATTRIBUTION. ONE OF THE REASONS THAT DATA IS NOT SHARED IS BECAUSE WHY WOULD I AS AN INVESTIGATOR SHARE MY 300 RARE PATIENTS WITH YOU FOR FREE? THAT'S CRAZY. THAT'S HOW I MAKE MY MONEY. SO WE HAVE TO BE ABLE TO RETURN A 5X ON THESE FOLKS, LET'S TALK CARROT AND STICK. CARROT IS IF WE CAN EVERY TIME THAT DATA IS USED, YOU GET CREDIT AND THEREFORE YOU CAN USE IT FOR PROMOTION BY USING A PERSISTENT IDENTIFIER, THAT'S A NICE LITTLE PULL, A CARROT. WE'RE OPENING YOUR DATA TO BE USED BY LOTS OF PEOPLE, YOU ALWAYS GET CREDIT FOR IT. THERE'S A STICK COMING DOWN THE PIKE WHICH IS MORE AND MORE AGENCIES, NIH, FDA, ARE GOING TO CONTINUE TO INSIST DATA IS FAIR, AND SO WE NEED TO GET AHEAD OF THE GAME, THAT OUR CTSAs CAN MAKE THEIR DATA FAIR BECAUSE IT'S ACTUALLY GOING TO BE A MANDATE. WE HAVE AN OPPORTUNITY HERE TO FINALLY MOVE THE DATA AROUND AND GET PEOPLE TO SHARE IT. WE'RE GOING TO MOVE TO THE NCATS CLOUD. I'M NOT GOING TO TALK ABOUT SPECIFIC HOW THE CLOUD IS PUT TOGETHER BUT HOW WE'RE USING IT IN THE CTSA. THE CLOUD IS QUITE A SEE CHANGE, IF YOU THINK ABOUT ONE OF THE THINGS IT DOES, ONE OF THE DIFFICULT THINGS FOR ME, MIKE, CHRIS, CONVINCING THE CTSA WORKING TOGETHER IS A GOOD IDEA. IT'S REALLY TOGETHER. THE CLOUD OFFERS AN OPPORTUNITY FOR COLLABORATION. IT HAS ITS OWN CARROTS AND STICKS. IT'S CHEAPER. ONE OF THE THINGS IT'S ACTUALLY DEMOCRATIZING COLLABORATION. I.T. IS REALLY EXPENSIVE. I'LL GIVE AN EXAMPLE, GOOGLE GOING TO HIRE AN UNDERGRADUATE NOW WITH TRAINING IN MACHINE LEARNING FRESH OUT OF COLLEGE FOR ABOUT $150K TO 300K, NEVER HAD A JOB, EXPERIENCE IT'S WITH MACHINE LEARNING 300K EASY AS GOOGLE NOW. HOW ARE WE GOING TO MAINTAIN STAFF TO DO I.T. WHEN IT'S A DIFFICULT CALL BECAUSE THEIR PAY STRUCTURE IS DIFFERENT FROM A GOOGLE, IT'S NOT AN EASY -- ONE OF THE THINGS THE CLOUD OFFERS IS ABILITY TO CONSOLIDATE THESE SKILLS AND HAVE LESS OF THEM BUT IN A CENTRAL SPOT. IT DOES THINGS WE NEVER HAD BEFORE, LIKE IF WE HAVE A CONTRACT TO BUY A PIECE OF SOFTWARE IN THE FEDERAL GOVERNMENT IT WILL TAKE 24 MONTHS FOR THAT CONTRACT TO GO IS YEARS, COMPANIES HAVE PUT IT IN PERSPECTIVE, iPHONE IS TEN YEARS OLD. SO TWO YEARS TO BUY A PIECE OF SOFTWARE IS A LONG TIME IN THE I.T. WORLD. IN THE CLOUD WORLD, YOU'RE RENTING SOFTWARE. FOR THE FIRST TIME WE CAN EFFECTIVELY EFFICIENTLY COST EFFECTIVELY GIVE PEOPLE TOOLS ALWAYS CURRENT. SO, THE OTHER THING, I WANT TO TALK ABOUT A SAS MODEL, SOFTWARE AS A SERVICE. RIGHT NOW WE'VE BEEN PAYING INFRASTRUCTURE FOR EACH OF THE CTSAs, SO THE LITTLE ACADEMIC CENTERS ON THE LEFT THERE. THE LITTLE KINGDOMS. AND EACH KINGDOM, WE ACTUALLY PAID TO PUT A PIECE OF SOFTWARE THERE. THERE'S SPARC, A COOL PIECE OF SOFTWARE, BUT WE'VE PAID FOR IT NOW AT 16 INSTITUTIONS. IF WE PUT IT IN ONE SPOT ON THE CLOUD, THEY ALL COULD SHARE IT. EVEN MORE COOL, THE WHOLE POINT OF SPARC IS IT'S SUPPOSED TO BE A MARKETPLACE, WHERE IS THE CHEAPEST PLACE TO GET AN EKG, THE PLACE I CAN FIND AN INVESTIGATORS WHO DOES THIS? IN THE CLOUD WE HAVE A COMPARISON ACROSS THE CTSA, NOT JUST SOUTH CAROLINA. THAT'S THE GOAL. WE'RE LOWERING OUR COST BUT ALSO INCREASING THINGS WE WANT, SHARING, WORKING TOGETHER, INCREASED SECURITY. THE OTHER THING WE'RE DOING IN THE NCATS CLOUD AND CD2H IS THE SANDBOX. THIS IS A SANDBOX. THEN WE PUT TOOLS IN IT. AND THEN WE PUT PEOPLE IN IT. AND THE PEOPLE WORK TOGETHER AND THEY CREATE A SAND CASTLE. AND SO WE ACTUALLY ARE CREATING SANDBOXES FOR THINGS THAT WE REALLY NEED PEOPLE TO WORK ON TOGETHER THAT RIGHT NOW THEY ARE WORKING ON SEPARATELY. ONE I'M GOING TO USE AS EXAMPLE, ONE MORE MACHINE LEARNING, NATURAL LANGUAGE PROCESSING, A GREAT EXAMPLE. YOU ALL HAVE DECIDED THERE'S ROUGHLY 7,000 DISEASES, WHO KNOWS WHAT THE NUMBER IS, SOMEWHERE IN THAT ZONE. ROUGHLY WHEN WE GET A PROPOSAL, MIKE GETS A PROPOSAL TO DO NLP FOR A SINGLE DISEASE, IT'S A MILLION DOLLARS PER DISEASE TO COME UP WITH PHENOTYPE BECAUSE WE HAVE TO PAY FOR TOOLS, INFRASTRUCTURE AND SCIENTISTS. $7 TRILLION FOR EVERY DISEASE, WHICH IS NOT GOING TO HAPPEN, WE HAVE TO HAVE ECONOMY OF SCALE. WE'RE CREATING NLP SANDBOX TO SHARE TOOLS, ALGORITHMS PRODUCED, SAND CASTLE, WILL BE COMPETED AGAINST EACH OTHER, THE ONE THAT DOES THE BEST JOB WILL GO ON THE APP STORE TO BE DISTRIBUTED, ENCOURAGING BOTH COMPETITION AND COLLABORATION. WE HAVE PEOPLE SAYING CAN YOU DO THE BEST JOB AT THIS AND WHOEVER HAS BEST JOB WE PUT IT ON THE STORE, EVERYBODY CAN GET IT FOR FREE. SO, I'M COMING TO THE END OF WHAT I WANT TO TALK B ALL I'M ABOUT. DATA COLLECTION IN GREEN, DATA USES IN BLUE, DATA SHARING IN RED, YOU CAN SEE THAT THIS IS REALLY THE FOCUS OF THE CD2H, MAKING THAT DATA INTEROPERABLE IN EVERY POSSIBLE WAY. AND WITH THAT I WOULD LOVE YOUR INPUT. I SAID Y'ALL, I'M FROM NORTH CAROLINA, THAT CAME OUT OF MY MOUTH, DIDN'T MEAN TO ADMIT. I WOULD ACTUALLY LOVE TO HEAR WHAT YOU HAVE TO SAY ABOUT EHRs AND FHIR WORK WE'RE DOING, HOW TO ACCELERATE THIS PROCESS BECAUSE CD2H IS -- I CAN'T COMPLAIN THAT I FEEL LIKE WE DON'T HAVE ENOUGH FUNDING. I'M GRATEFUL FOR EVERYTHING WE HAVE BUT I COULD SPEND 14 TIMES AS MUCH AS WE SPEND BECAUSE I.T. IS JUST EXPENSIVE AND THERE'S A LOT OF THINGS WE NEED TO DO. AND THEN THE CTSA CLOUD INITIATIVE IS A GAME CHANGER TO GET THE COMMUNITY TO WORK TOGETHER, I'M EXCITED ABOUT IT BUT IT'S A COMMITMENT WE'RE SAYING WE'RE GOING TO BUILD SOMETHING WE EXPECT CTSA TO USE TOGETHER. AND THAT'S GOING TO TAKE LONG-TERM COMMIT MENT FROM US, I WOULD LOVE TO HEAR YOUR FEEDBACK AND COMMENTS. >> THANK YOU, KEN. I WANT TO DEMONSTRATE I WROTE DOWN I'VE GOTTEN MY CQL AND FHIR SERVER FROM YOUS CDM ADAPTER, AGGREGATED RESULTS TO THE CROWD. HOW DID I DO? I HAVE NO IDEA WHAT I JUST SAID. [LAUGHTER] KEN IS REALLY LEADING US IN SOME AMAZING DIRECTIONS. PLEASE, FEEDBACK. >> I THINK THIS IS VERY CRITICAL WORK, ONE OF THE KEY ISSUES OUR ECOSYSTEM IS STRUGGLING WITH. WHEN WE THINK OF ALL THE EPICS, INSTALLATIONS, PROBABLY 50,000 AROUND, RIGHT? THE LACK OF INTEROPERABILITY, THIS PILOT FOR THE ECOSYSTEM IS CRITICAL. SO TO BE SURE, I'M VERY SUPPORTIVE OF IT. I'M ALSO ASKING HOW FDA CAN HELP. WE HAVE DATA SOURCES THAT MIGHT BE SUPPORTIVE AND HOW WE CAN COLLABORATE TO LINK CRITICAL DATA SOURCES, PARTICULARLY FOR CLINICAL RESEARCH, THAT HAVE REAL CLINICAL DATA IN IT, PATIENT DATA, THAT'S PERHAPS A SEPARATE DISCUSSION THAT GOES BEYOND RIGHT NOW, BUT TO BE ABLE TO HAVE A REUSABILITY OF PCORI, SENTINEL, IN A WAY A MANDATE THAT HHS AND SPECIFICALLY FDA HAS, NAMELY SAFETY OF PATIENTS. SO I'LL EXTEND SUPPORT. >> MY PARTNER IN CRIME AT THE FDA IS MITRA RAKA, A WONDERFUL, WONDERFUL PERSON. WORKS A ZILLION HOURS. WE'RE NOT TALKING ABOUT AGGREGATE DATA BUT PULLING LINE LEVEL DATA. AND FOR THE INITIAL PROTOTYPE WE PULLED LINE LEVEL DATA ON SOME CANCER DRUGS, AND WE'RE SUCCESSFUL DOING THIS SO WE'RE PRETTY EXCITED ABOUT THAT AND DID SUBMIT THROUGH THE FDA GATEWAY, SO WE TRANSFORMED IT ALL THE WAY FROM EMR DATA INTO SETM, A CONVOLUTED PATH BUT IT DOES GET THERE. AND THIS IS PART OF PHASE 2, DEFINITELY. >> A GEEKY QUESTION, I SPENT TIME TRYING TO GET INFORMATION FROM EHRs, IT'S THEY HARD. ARE YOU MAPPING EPIC FIELDS TO FHIR, REQUIRING EPIC FIELDS TO BE FHIR? >> A REALLY GOOD QUESTION. ONC AND CMS ARE MANDATING THAT FHIR, THAT EPIC AND ALL EHRs ARE GOING TO SUPPORT SOMETHING CALLED BULK FHIR. AND BULK FHIR IS A SPECIAL PULL FOR PUBLIC HEALTH INFORMATION, SO ORIGINALLY FHIR WAS I KNOW MR. JOHNSON'S MEDICAL RECORD NUMBER, PLEASE PULL MR. JOHNSON, ALLOW HIM TO PUT IT ON A THUMB DRIVE AND GO DOWN THE STREET WITH HIS DATA. BUT BULK FHIR, BEING MANDATED, I DON'T KNOW IF THEY ARE GOING TO CALL IT PHASE 3, THAT'S GOTTEN A LITTLE BIT CHANGED, BUT IT WILL BE MANDATED PROBABLY BY THE END OF NEXT YEAR, THAT EPIC AND ALL OF THEM WILL HAVE TO TRANSFER THEIR DATA THROUGH BULK FHIR. THE ISSUE WITH THIS, NOT TO GET TOO MUCH INTO THE WEEDS, WE'RE WORKING WITH OFFICE OF NATIONAL COORDINATOR, OUR FIRST SET OF DATA FROM BULK FHIR IS U U.S. CORE, GUARANTEEING THE SAME FIELDS BUT I THINK WHERE YOU'RE GOING WITH THIS HOW DO WE DO WEIRD MAPPINGS CAN ALL THE OTHER STUFF. THAT ALLOWS SELF MAPPING TO BE PART OF THE MAPPING. I WON'T MAP EACH INSTITUTION TO PARTICIPATE, TO BUT THEY HAVE TO KEEP THEIR DATA MAPPED TO THE TERMINOLOGY SERVICES, THAT'S WHAT IT DOES. >> I THINK FOR THOSE OF US WHO HAVE WILL BE OBSESSED WITH DATA FOR DECADES, THIS IS A DREAM COME TRUE TO ACTUALLY BE ABLE TO PULL ALL THIS TOGETHER IN A WAY, REALLY CAPTURE DATA, IN WAYS THAT HAVE NOT BEEN POSSIBLE BEFORE. SO, I WONDERED, I THINK PULLING THIS CTSA DATA TOGETHER IS A GREAT STEP. IT TIES IN WITH DISCUSSIONS WE HAD ABOUT RARE DISEASES BEFORE, WHERE ONE COULD REALLY BEGIN TO PULL ON QUESTIONS THAT HASN'T BEEN ABLE TO BEFORE, BECAUSE OF DISPARITY OF HOW THE DATA WAS COLLECTED. BUT WHERE DO YOU ENVISION WITH THIS GOING BEYOND THE CTSA BECAUSE I WOULD THINK IT WOULD BE MANY CUSTOMERS THAT WOULD WANT ACCESSIBILITY TO THIS AS WELL AS ALSO POTENTIAL DONORS, RIGHT, TO THIS HUGE CLOUD AND PHARMA HAS VAST DATA, NOT JUST ON DRUG-TREATED PATIENTS WHICH MAY BE MORE RELUCTANT TO SHARE INITIALLY BUT FOR EXAMPLE CONTROL GROUPS, FROM DISEASE STATES, THAT ARE VERY WELL CHARACTERIZED THAT COULD ADD REALLY A WHOLE NEW ADDITIONAL DIMENSION TO THIS. >> A REALLY GOOD QUESTION. YOU BRING UP SOME THINGS THAT ARE NO SOLVEED IN THIS PUZZLE. PART OF CD2H'S JOB IS TO CREATE A DATA USE AGREEMENTS AMONG CTSAs, NOT AN EASY TASK BECAUSE OF POLITICS, NOT TECHNICAL, I CAN GO INTO THAT BUT THAT DOESN'T MATTER IF WE CAN'T GET IT TO BE DONE. IT WILL BE LIKE THE RELIANCE AGREEMENT WITH SMART IRB, GET PEOPLE TO SIGN UP AND BASICALLY TRY TO GET THEM TO DO -- WE CAN MAKE IT SO IT'S FLEXIBLE, IT'S NOT ALL OR NOTHING. THIS IS, TO BE CLEAR, THIS PICTURE -- THIS THING IN BLUE IS CALLED AN APPLIANCE, ALL GETS PUT INTO ONE BOX, AND WE PUT IT AT THE INSTITUTION. SO FOR $5,000, $10,000 WE COULD PUT ONE AT EVERY CTSA, IT'S JUST NOT THAT MUCH MONEY WHEN YOU THINK ABOUT IT. AND BUT THE GREEN ARE THE AGENCIES, LIKE HHS, AND SO EACH ONE OF THOSE WILL HAVE THEIR OWN INSTALLATION BUT THEY SHARE THE BLUE. DATA FOR CDC IS IDENTIFIED DATA, GOES TO THE STATES FOR MEDICARE, THE DATA GOING TO FDA, WE WOULD LIKE A QUESTION ON IMMUNOTHERAPIES CAUSING DISEASE, THE TOOL IS REALLY AN HHS TOOL, NOT SUPPOSED TO BE AN NCATS TOOL. IT'S ALL REUSABLE KIND OF GENERIC STUFF ON PURPOSE. SO PEOPLE CAN REUSE IT. SO I'M NOT SURE I ANSWERED YOUR QUESTION. ONE OTHER THING, IT'S NOT PLANNED TO BE A DATA PALACE. WHEN I SAY THAT I MEAN WE'RE NOT HERE TO BE THE MOUNTAIN OF THE TRUTH OF DATA, THAT'S NOT WHAT THIS IS. IT'S A TRANSPORT MECHANISM. GETTING TO SHARE IS ONE THING, PUTTING IT IN YOUR BOX IS EXPENSIVE, THIS IS CALL FEDERATED ANALYTICS, WE'RE DOING QUERYING ON THEIR DATA, AT THEIR SITE, COMING BACK WITH THE ANSWERS OR LINES, SOMETIMES, BUT WE'RE NOT ACTUALLY PULLING ALL OF THEIR DATA. SO IT'S REALLY THEIR DATA STAYS IN THE BLUE. AND THAT'S AT THEIR SIDE OF SITE BEHIND THE FIRE WALL. >> I'M SURE MY QUESTION WILL BE SIMPLISTIC AND DEMONSTRATE MY IGNORANCE. I'VE GOT TO PULL TECHNOLOGIES INTO A DOMAIN I KNOW A LITTLE BIT ABOUT. THAT IS, WHEN ANNE PARISER GAVE HER EXCELLENT PRESENTATION SHE MENTIONED I THINK THAT WILL DMCC IS BEING PUT ON THE CLOUD. I'M WONDERING TO WHAT EXTEND THESE TECHNOLOGIES WOULD BE LIKE FHIR, WOULD BE USED TO DO THAT AND WHAT THE NET EFFECT WOULD BE? >> EVERYTHING WE'RE DOING AT NCATS AT THE CTSA, FOR THE CTSA AT NCATS IS SHARED WITH ORDR, ONE PLATFORM ACROSS THE ENTIRE NCATS CONTINUUM. THE SPECIFIC WAS FHIR, MAYBE IT'S A LITTLE DIFFERENT AND THAT WE CAN PULL DATA IN FHIR FROM A REGISTRY, OR RESEARCH PROTOCOL. THERE'S A LOT OF THINGS WE HAVE TO TALK ABOUT BUT WHAT DATA SETS WE DECIDE, BUT I THINK GOING -- I DON'T MEAN TO PONTIFICATE, BUT FHIR IS -- THINK ABOUT HEALTH CARE, IT'S THIS BIG IN DOLLARS. IF YOU THINK ABOUT RESEARCH, IT'S THIS BIG. WHAT HEALTHCARE SPENDS IN A DAY IS WHAT NIH IN AN HOUR -- IN AN HOUR IS WHAT THE NIH SPENDS IN A YEAR. BY USING THE FHIR STANDARDS, EHR STANDARDS, AND BILLING STANDARDS, WEB MD, WE'RE STANDING ON THE SHOULDERS OF A LOT MORE POWER TO GO TO THOSE STANDARDS. SO ON PURPOSE I'M KIND OF LEVERAGING THAT. SO I -- I WOULD ADVOCATE THAT THAT THE DATA SHOULD BE COMING IN IN FHIR RESOURCES ACROSS THE COUNTRY. I THINK THAT THAT'S WHAT THE NIH'S ANNOUNCEMENT MEANS. THIS IS WHAT THEY ARE EXPECTING. IN FHIR RESOURCE, LIKE ALLERGIES, IT SAYS THIS IS ALLERGIES, I EXPECT IT TO COME IN THIS FORMAT. AND I EXPECT VALUES TO HAVE THESE NUMBERS AND THIS IS THE VERSION OF THAT RESOURCE. COMPUTER SAYS THIS IS VERSION FROM JANUARY, I KNOW THAT MALE IS 1, FEMALE IS 12. IF A VERSION FROM, YOU KNOW, 2021, FOR WHATEVER REASON CHANGED, I CHANGED VALUE OF MALE TO 2, SO WHAT'S NICE IS IT'S MACHINE READABLE, TELLS US WHAT'S IN THE BOX. >> IF I MAY REITERATE, THAT PHASE OF DEMONSTRATION IS VERY CRITICAL. I ALSO WOULD LIKE TO PUT A PLUG IN FOR 70% OF THE DATA IN THE EHR, CLINICAL LABORATORY DATA, OR IMAGING DATA, AND THERE WE OFTEN BREAK THE AUDIT TRAIL, THE CHAIN. IT DOESN'T GO FROM THE LABORATORY INFORMATION MANAGEMENT SYSTEM INTO THE EHRs BECAUSE THERE'S ONLY PROBABLY THREE COMPONENTS TRANSFERRED. AS A CONTINUING PHASE, IT'S VERY IMPORTANT TO ALSO HAVE THAT VISION TO INCLUDE CLINICAL LABORATORY DATA IN STANDARDIZED ACCESSIBLE AND INTEROPERABLE WAY. THE PROVENANCE AND STRENGTH OF THE EVIDENCE AS IT IS USED CURRENTLY DEPENDS ON INCLUSION OF THE AUDIT TRAIL TO THE CLINICAL LABORATORY DATA, AND I KNOW YOU'RE AWARE OF IT, BUT I DO NEED TO STATE THAT BECAUSE THERE ARE -- THERE'S CERTAINLY A LOT OF WORK TO DO. >> YOU'RE RIGHT. WE ARE AWARE. WE'RE ALSO AWARE IT'S A DIFFICULT PROBLEM, PROVENANCE IS IMPORTANT, NOT TO GET GEEKY BUT THE POINT OF TERMINOLOGY SERVICE, REAGAN STRIFE MAINTAINS LOW INK DATA, DICTIONARIES, BUT WE'RE USING THOSE TO INFORM THE RESOURCES. SO INSTEAD OF EVERYBODY HAVING TO BE THEIR LOCAL MAPPING, LOINCC, WE USE THE TERMINOLOGY SERVICE TO DO THE INTERPRETATION SO THAT'S KIND OF HALF YOUR QUESTION. THE OTHER HALF IS OTHER TYPES OF DATA, AND JUST TO BE -- TO PUT ANOTHER PLUG FOR FHIR, APPLE USES FHIR FOR THE APPLE WATCH. GOOGLE NOW HAS A FHIR REPOSITORY THEY ARE SELLING, SO DOES MICROSOFT. AND IN THE EVERY GEEK WAY THERE'S A COMPANY CALLED LONK, MY FAVE IT -- MY FAVORITE. LARGE COMPANY ARE INVESTING, THEY SEE MONEY IN IT, A WAY TO MOVE DATA QUICKLY AND EASILY. I AGREE WITH WHAT YOU'RE SAYING. IT'S IMPORTANT. >> OKAY. VERY GOOD. >> THANK YOU. >> THANK YOU, KEN. THAT WAS GREAT. [APPLAUSE] >> WE HAVE A FEW MINUTES LEFT, OFFICIALLY ANOTHER 28 MINUTES, BUT WE COULD TAKE AS MUCH TIME AS WE WANT. OR AS LITTLE TIME AS WE WANT. WE'RE REALLY INTERESTED IN IDEAS OR THINGS THAT YOU WOULD LIKE TO HEAR ABOUT WHEN YOU'RE ON YOUR WAY HERE, YOU'RE THINKING, GOSH, I WISH I KNEW WHAT NCATS WAS GOING IN X. OR WHAT ARE KNUCKLEHEADS DOING, WHY HAVEN'T THEY SOLVED THAT PROBLEM? THAT'S WHAT WE'RE INTERESTED IN HEARING ABOUT FROM YOU BECAUSE WE HAVE TO CHOOSE EVERY TIME WHICH THINGS WE THINK YOU'LL BE INTERESTED IN BUT AS YOU KNOW WE LIKE TO DO COMMUNITY ENGAGEMENT AROUND HERE AND FIND OUT WHAT YOU ACTUALLY WANT TO HEAR ABOUT BECAUSE THAT'S GOING TO BE MOST INTERESTING. CERTAIN THINGS WE HAVE TO TELL YOU ABOUT, CLEARANCES AND THINGS LIKE THAT. BUT ARE THERE THINGS THAT PIQUE YOUR INTEREST OR THINGS YOU'D LOVE TO HEAR MORE ABOUT, THINGS THAT YOU NEVER WANT TO HEAR AGAIN, SUCH AS THE DIRECTOR'S UPDATE, OR OTHER THINGS. SO THE MIC'S OPEN AT THIS POINT. >> IS THE UNDIAGNOSED PROGRAM UNDER NCATS? >> IS THE WHAT? >> UNDIAGNOSED DISEASE. >> OH. WE'RE NOT OFFICIALLY PART OF THE UDN, IT'S A COMMON FUND PROGRAM, STILL FUNDED BY THE COMMON FUND FOR ANOTHER COUPLE YEARS. AND THERE ARE CONSIDERABLE QUESTIONS WHAT'S GOING TO GO ON WHEN THE UDN ENDS. AND WE'VE BEEN INVOLVED IN THOSE, IN A WAY IT WOULD BE A NATURAL THING FOR US BECAUSE MOST OF THE UDN PATIENTS WHEN THEY BECOME DIAGNOSED, THEY ARE RARE DISEASES FOR THE MOST PART. SO THEY ARE OUR FARM TEAM. HOWEVER, IT'S A RATHER EXPENSIVE PROGRAM. SO, IT WOULD HAVE TO COME WITH THE MONEY. AND ACCORDING TO RULES OF COMMON FUND IT CAN'T. SO THAT'S THE PICKLE THAT WE'RE IN. IT'S LIKE IN MOST THINGS, IN NCATS, WE'RE INNOVATIVE, COLLABORATIVE, AND POOR. SO, YOU KNOW, SCIENTIFICALLY AND ORGANIZATIONALLY IT MAKES SENSE BUT WHAT WILL HAPPEN IN THE NEXT COUPLE YEARS IS UNCLEAR. WHAT ELSE WOULD YOU LIKE TO HEAR ABOUT OR NOT HEAR ABOUT? >> I THINK WE TALKED ABOUT IT A LITTLE BIT EARLIER TODAY, THAT IS WHAT'S THE IMPACT OF THE DECISIONS WE'RE MAKING IN TERMS OF THE FUNDING AND MORE OF A FEEDBACK LOOP ON WHAT THAT DOES. I THINK ONE OF THE CHALLENGES IS, HOW DO WE AS A GROUP DO MORE THAN FEEL LIKE SOME OF THE RUBBER STAMP PARTS OF THE PROCESS. >> RIGHT. >> I KNOW IT'S HARD TO KEEP IT FROM FEELING THAT WAY BUT THERE IS A TENDENCY TO THINK WE JUST LOOK AT ALL THESE. >> CLOSED SESSIONS PARTICULARLY? >> HAVE WE EVER SAID NO TO ANYTHING? >> RON HAS TRIED MULTIPLE TIMES. >> MAYBE DIALOGUE THAT FEELS PROCESSY BUT MAYBE THAT AS WELL AS WHAT HAPPENS WHEN WE DO VOTE ON THINGS, WHERE DOES THE MONEY GO, WHAT ARE THE RESULTS THAT COME OUT OF THOSE. >> YEAH. >> WHETHER IT'S A PUBLICATION OR SOMETHING THAT GETS DONE, I THINK THE LOOP OF WHAT HAS HAPPENED AS A RESULT OF WHAT WE'VE DONE. >> GOOD POINT. IN JANUARY OF EVERY YEAR I TRY TO DO A BIT OF THAT BUT UP UNTIL NOW IT'S BEEN MAINLY WHERE DID THE MONEY GO. YOU DO EN BLOC CONCURRENCE BUT WHAT DO WE FUND, A DIFFERENT QUESTION. IT DEVOLVES INTO LISTS OF GRANTS, AND GRANTS ARE PROMISSORY NOTES, IT TELLS US WHERE THE MONEY WENT, NOT UNUSABLE, BUT WHAT YOU WANT TO KNOW IS, WELL, WHAT ACTUALLY HAPPENED IN ACCOMPLISHMENT POINT OF VIEW >> (INAUDIBLE). >> YEAH, RIGHT, ALL THAT STUFF. YOU SHOULD KNOW THAT THE DISCUSSIONS THAT ALL THE PRESENTATIONS THAT YOU GET, WHETHER INFORMATICS OR RARE DISEASES OR WHAT HAVE YOU, WERE THE RESULT OF DISCUSSIONS THE COUNCIL AND CAN BOARD HAD, BUT THEY WOULD HAVE BEEN LIKE FOUR OR FIVE YEARS AGO BEFORE ANY OF YOU WERE ON THE BOARD. THAT'S THE PROBLEM. A TYPICAL PROGRAM IS FOUR OR FIVE YEARS, TIME TO GO FROM GRANT TO SOMETHING WHICH MAKES IT INTO LITERATURE IS FOUR OR FIVE YEARS AND BY THAT TIME EVERYBODY IS NEW. YOU NEVER -- BUT WE'LL THINK ABOUT THAT, ABOUT HOW TO MAKE THIS -- IN THE JANUARY MEETING. >> A LOT OF WHAT KEN DESCRIBED WITH INFORMATICS IS DONE THROUGH THE CD2H, AN INITIATIVE, I CAN'T EVEN THINK HOW LONG AGO. >> (INAUDIBLE). >> I CAN'T TELL YOU WHEN BECAUSE IT PREDATED ME BUT THAT CONCEPT CLEARANCE WOULD HAVE COME THROUGH THREE OR FOUR YEARS AGO. SO, WHAT YOU SEE, WHAT KEN PRESENTED, IS THE RESULT OF A CONCEPT THAT COUNCIL HEARD, DISCUSSED, AND APPROVED AND NOW YOU'RE SEEING THE OUTPUT OF WHAT THAT IS PRODUCING. >> IT'S IMPORTANT TO REALIZE THAT IN ADDITION TO THAT LAG, THERE'S OFTEN -- WHEN WE GET A CONCEPT APPROVED IT DOESN'T NECESSARILY MEAN WE'RE GOING TO ISSUE THAT FOA WITHIN SOME PARTICULAR TIME FRAME OR CONFIGURED A TYPICAL WAY. SOME I.C.s SPECIFY MECHANISM, MAY TALK ABOUT DOLLAR AMOUNTS. WE'RE DELIBERATELY VAGUE AT THIS TAGE BECAUSE CONCEPTS NEED TO MATURE. AS WE HAVE CONVERSATIONS ABOUT THE BEST WAY TO GO ABOUT IT, WE MAY THEN DECIDE WHICH MECHANISM IT'S GOING TO BE. FOR THE EN BLOC PANELS WE DO PRIDE THE DATE THE CONCEPT WAS CLEARED IN YOUR DOCUMENT SO YOU HAVE THAT FRAME OF REFERENCE. I THINK MOST TIMES TO MIKE'S POINT WHAT YOU SEE IS, I WASN'T A MEMBER AT THAT POINT. WHAT WE HAVEN'T DONE IS TIED THAT INTO THE PRESENTATIONS, AND THE OTHER DIRECTION WE HAVEN'T REALLY CLEARLY IDENTIFIED WHAT'S THE PRODUCT THAT'S STARTED WITH THAT INITIAL CONCEPT. IT'S AN END TO END THING WE CAN DO. >> IT DOES OCCUR TO ME IT WOULDN'T BE HARD FOR US, I THINK BIT, I NEVER THOUGHT ABOUT THIS, SO THANK YOU FOR RAISING IT, KEN COULD HAVE STARTED WITH ONCE UPON A TIME THERE WAS A CONCEPT CLEARANCE, IT SAID THIS. AND THEN THERE WAS AN RFA THAT SAID THIS. AND THIS IS WHAT WE WERE TRYING TO GET OUT OF THIS, THIS IS WHAT WE GOT OUT OF IT. WHICH I WOULD FIND REALLY INTERESTING. I CAN'T REMEMBER WHAT THE CONCEPT CLEARANCE SAID, HOW MANY YEARS AGO IT WAS. IT WOULD REALLY BE INTERESTING. THAT'S A GREAT SUGGESTION. WE SHOULD DO THAT. >> WE'RE PUTTING IN PLACE SOME -- WE STARTED PUTTING IN PLACE LIKE WE TALKED ABOUT THIS MORNING WITH THE GENE THERAPY, REPURPOSING, YOU COULD SEE HOW THAT STORY, IF WE HOLD IT TOGETHER, ALTHOUGH MANY OF US WON'T BE HERE, BY THE TIME THOSE THINGS START READING OUT THAT CHRONOLOGY ALLOWS I THINK THE GROUP TO UNDERSTAND WHAT IT IS THEY ARE DOING, WHY THEY ARE DOING AND IMPLICATIONS, OTHERWISE WE'RE TAKING A SNAPSHOT. YES, YES, OKAY. >> REALLY GREAT POINT. WE CAN DO THAT IN WAYS OTHER INSTITUTES CAN'T. IF YOU'RE FUNDING R01s, THERE NO DELIVERABLE AT THE BEGINNING, JUST DO INTERESTING STUFF. EVERYBODY DOES INTERESTING STUFF. IT'S BEEN POINTED OUT YOU PUT IN THE NUMBER OF DOLLARS, YOU GET A PAPER. BUT IN THIS CASE WE'RE TRYING TO GET SOMETHING ACCOMPLISHED BEYOND A PUBLICATION. >> IT'S VERY IMPORTANT. >> WHAT DO WE THINK WE'RE DEVELOPING? IT'S INTERESTING. >> SOMEWHAT RELATED TO THAT, SOMETIMES WE HEAR DIFFERENT TOPICS, IT BLENDS TOGETHER TECHNOLOGY DEVELOPMENT AND APPLICATION. AND SOMETIMES IT GETS A LITTLE BIT CONFUSING IN TERMS OF WHERE THINGS ARE FROM MATURITY STANDPOINT, AND WHERE SOME OF THE APPLICATIONS ARE GOING, ESPECIALLY WITH PARTNERS THAT NCATS HAS. INTRAMURAL PROGRAM, ALSO HOW IT EXTENDS OUTSIDE. I THINK SOME STRUCTURE AROUND THAT WOULD BE HELPFUL IN TERMS OF HOW THINGS ARE REPRESENTED, BECAUSE I THINK WHAT WOULD HELP THIS GROUP TOO IS LOOK FOR CONVERGENCE OPPORTUNITIES AND SYNERGIES, AND I THINK WE'RE HEARING SOME BEGINNING EMBEDDED, DIFFERENT PROGRAMS ARE STARTING TO USE COMMON TOOLS. AGAIN, THINK BACK TO THE OVERALL GOAL MISSION OF NCATS. TRANSFORMATION FROM SINGLE TOOLS, APPLICATION, IT'S REALLY THE COMBINATION OF THINGS. THINK ABOUT THE LAST TIME WE HEARD ABOUT THE TRANSLATOR, OKAY, AND THINKING ABOUT HOW THAT MATURES, HOW CAN IT CONNECT AND IMPACT SOME OTHER PROGRAMS ONGOING AND HOW IS THAT BEING USED TOGETHER. I THINK THESE ARE THE THINGS THAT CAN BE REALLY HELPFUL, THINKING OF A SYSTEMS APPROACH THAT NCATS IS ON A PATH TOWARDS. AT LEAST HOW I LOOK AT IT. I'M TRYING TO UNDERSTAND INDIVIDUAL PROGRAMS, TRYING TO THINK ABOUT HOW THEY CONNECT TO ONE ANOTHER, HOW YOU GET MORE BANG FOR THE BUCK WHEN YOU LEVERAGE COMMON PLATFORMS TOGETHER BECAUSE THAT'S HOW YOU REALLY IMPACT CHANGE. AND SO MAYBE THINKING ABOUT FRAMING SOME OF THE CONTENT IN THAT WAY CAN HELP THE GROUP THINK ABOUT IT IN A MORE SYSTEM WAY. >> YEAH, THE V.A. IS OBVIOUSLY UNIQUE FROM NIH IN THAT WE'RE PART -- RESEARCH IS INTRAMURAL AND PART OF A HEALTH SYSTEM. SO, THERE ARE GREATER DEMANDS TO GET THE RESULTS OF THE RESEARCH INTO PRACTICE. AND THERE'S STILL SO MANY BARRIERS AND CHALLENGES, BUT ONE OF THE THINGS THAT HEALTH SERVICES AND WE'RE AT THE VERY END OF THE TRANSLATION, WE DON'T DO BIOMEDICAL RESEARCH, WE'RE RIGHT THERE BEFORE IMPLEMENTATION, AND SO WE'VE GOTTEN SOME FEEDBACK FROM OPERATIONS FROM THE SECRETARY IF YOU'RE GOING TO DO RESEARCH YOU BETTER MAKE IT WORK. IT'S GOT TO THE HAVE IMPACT. THEY DON'T HAVE SEVEN, EIGHT YEARS. I DON'T KNOW IF NCATS CAN DO THIS, CAN YOU DEVELOP FUNDING MECHANISMS THAT HAVE A MORE RAPID TURNAROUND? I ASK THAT BECAUSE THE INTERINITIATED AWARDS ARE FOUR TO FIVE YEAR AWARDS, LIKE R01s, THEY JUST TAKE TOO LONG. SO CAN YOU -- WE THOUGHT ABOUT TWO, THREE YEAR AWARDS, MAYBE LONGER AWARDS THAT HAVE MORE INTERMITTENT DELIVERABLES. AND I DON'T KNOW IF THAT'S SOMETHING THAT NCATS CAN DO. WE'VE HAD TO DO IT BECAUSE OF OUR DEMANDS. >> GREAT QUESTION. IT'S INTERESTING, THE EXTREME OF THAT IN THIS CASE WOULD BE THE "CAN" PROGRAM WHEN WE STARTED OUT, THE AWARDS WERE SIX MONTHS. AND YOU HAD TO DELIVER IN SIX MONTHS OR ELSE YOU WERE OUT. AND THAT WAS VERY MOTIVATING. THE PROBLEM THERE BECAME -- YOU COULD DO IT FOR A CERTAIN AMOUNT OF TIME BUT IT'S -- YOU CAN'T SUPPORT PEOPLE ON SIX MONTHS OF FUNDING BECAUSE EVENTUALLY YOU CAN ONLY SPRINT FOR SO LONG BEFORE YOU HAVE TO START USING THE SLOW TWITCH MUSCLES INSTEAD OF FAST TWITCH MUSCLES. THERE ARE A NUMBER OF PROGRAMS INCLUDING TISSUE CHIP AND INTRAMURAL PROGRAMS THAT HAVE A TURNAROUND TIME WHICH IS MUCH SHORTER, BECAUSE THEY ARE MILESTONE DRIVEN THEY CAN STOP AS SOON AS THE PROJECT FAILS. THEY STOP. AND WE'RE TRYING TO DO THAT WITH A NUMBER OF THE NON-HUB AWARDS IN THE CTSA PROGRAM, THOSE ARE SHORTER, LIKE A COUPLE YEARS. >> FOR VERY SPECIFIC PROJECTS, YES, THEY DO HAVE A ONE YEAR TURN AROUND. THE ONE DISTINCTION, THAT'S NOT AN ISSUE, BUT HEALTH CARE RESEARCH FUNDING IS GOING TO IS SEPARATE AND DISTINCT FROM THE HEALTHCARE, SOME SITUATIONS THE INSTITUTION THAT'S THE PARENT INSTITUTION IS PART OF AN INSTITUTION THAT DOESN'T ACTUALLY HAVE DIRECT OWNERSHIP OR AUTHORITY OVER THE HOSPITAL THAT THEY ARE ALIGNED WITH. SO THERE'S ANOTHER LAYER OF SEPARATION IN THE V.A. YOU'RE MUCH MORE EASILY INTEGRATED THAN WHAT WE SEE IN MOST ACADEMIC INSTITUTIONS. >> AND THE OTHER THING THAT -- WE PUT OUR -- WRAPPED OUR HEADS AROUND WHAT KIND OF FUNDING MECHANISM WE PUT OUT. I DON'T KNOW IF WE HAVE MORE FLEXIBILITY. THE OTHER APPROACH THAT WE'VE TAKEN IS WE FUND A LOT OF RESEARCH EVERY YEAR. THE INVESTIGATORS SEEM TO BE COMING BACK OVER AND OVER. I CALL THEM MORE PARAMETRIC RESEARCHERS, ONE LITTLE CHANGE AND THEY GET ANOTHER FIVE YEARS OF RESEARCH. WE CAN'T AFFORD TO DO THAT. AND SO WHAT WE'VE DONE IS WE'VE ADDED ANOTHER FUNDING MECHANISM WHERE WE WILL PROVIDE SUPPLEMENTAL FUNDS FOR THOSE INVESTIGATORS THAT ARE NOW READY TO TAKE IT TO THE NEXT LEVEL. SO THAT IF THEY'VE HAD FIVE YEARS OF FUNDING, MAYBE MORE, AND THEN WE GIVE THEM TWO, THREE YEARS MORE OF SUPPLEMENTAL FUNDS, WITH INTERMITTENT BENCHMARKS AND WHAT NOT, TO IMPLEMENT IT, THEN SCALE IT UP, AND THEN ACTUALLY HAVE SOME IMPACT, AND THE IMPACT COULD BE A VARIETY OF THINGS. IT'S NOT PAPERS THOUGH. SO THAT'S ANOTHER MECHANISM THAT WE'VE DONE >> THE PART OF THE GOVERNMENT WHERE I CONSULT FOR, USING A NEW MECHANISM, EASY BAA, A SHORT APPLICATION, TRUNCATED FUNDING, WITH EXPECTATIONS OF DELIVERABLES IN THAT TIME FRAME OF SIX MONTHS TO MAYBE 24 MONTHS, WHICH IS INTENDED TO STIMULATE THEM TO CREATE THE AMOUNT OF DATA THAT ALLOWS THEM THEN TO BE MORE SUCCESSFUL COMPETING FOR THE LARGER FUNDING THAT COMES AS A RESULT OF THAT. THEIR TIME LINE, TURNAROUND, THEY STRIVE TO DO IT WITHIN A MONTH OF RECEIPT OF APPLICATION TO BE ABLE TO AGREE FUNDING. SO IT'S VERY RAPID. NOT MILLIONS OF DOLLARS, RIGHT? THIS IS TENS OF THOUSANDS OF DOLLARS BUT JUST TO KEEP PEOPLE GOING AND DRIVE INNOVATION. >> CALLED -- >> E-Z-B-A-A. >> COUNCIL IS NOT THE SAME AS A CORPORATE BOARD, WE CONCUR AND ACT AS DISCUSSANTS. >> YOU FIRE THE CEO. >> HUGE DIFFERENCE, YOU HAVE NO IDEA. BUT IF I WERE A BOARD MEMBER, ONE THING I FEEL IGNORANT ABOUT IS CTSA PROGRAM, THE BIGGEST PART OF THE BUDGET, I SHOULD KNOW THAT. I GOT A SENSE WHEN I JOINED THIS COUNCIL FROM SOME OTHER COUNCIL MEMBERS IT WAS A SACRED COW WHERE YOU CAN'T PICK ON IT TOO MUCH BUT I WOULD LIKE TO UNDERSTAND IT SO I THINK IF YOU WERE STARTING FROM SCRATCH TODAY WHAT WOULD IT LIKE LIKE AND SHOULD IT DO THE THINGS BOLTED ON, WERE THEY ALL NECESSARY OR ONLY PIECES OF IT? I WOULDN'T MIND AS A COUNCIL MEMBER A TUTORIAL VERSION WITHOUT ACRONYMS IF POSSIBLE AND HEAR IT. IF YOU CAN'T DO THAT, MAYBE I CAN JUST CALL ANNA, CHANCES ARE ANNA KNOWS HOW IT WORKS AND SHE CAN JUST TELL ME. FLIP SIDE, COMING FROM US, I THINK IT WOULD BE INTERESTING LOOKING AT MY FELLOW COUNCIL MEMBERS TO HAVE EITHER A BRAINSTORM SESSION, WHERE WE TELL YOU EVERY ONCE IN A WHILE, ONCE A YEAR OR SOMETHING, ALL THE THINGS WE'RE SEEING AS OBSTACLES IN DRUG DISCOVERY, TRANSLATION, I COMPLAIN ABOUT THEM BUT WHATEVER THEY ARE, AND IT COULD BE THINGS LIKE WEARABLE DEVICES FOR BETTER READ OUT, YOU HEAR ABOUT NEW TECHNOLOGY EMERGING, THE REASON I SAY ALL THIS YOU ARE AWARE OF THESE PROBLEMS AND GAPS AND YOU PROBABLY KNOW MORE ABOUT THE LANDSCAPE OF WHAT'S COMING THAT COULD HELP, BUT IT FEELS LIKE WE GET SHOW AND TELL WHEN WE COME HERE AND GET SOME REALLY COOL THINGS SHOWN TO US BUT WE NEVER SEE THE WHOLE MENU. AND THE PRICES TOO. TO SEE LIKE IF YOU COULD ONLY DO SOME WHICH WERE YOUR FAVORITES. INSTEAD DO YOU THINK THIS PROGRAM IS COOL? OH, IT IS COOL, WE LIKE THAT ONE. WE LIKE THAT ONE. BUT IT'S NOT AN INFINITE WORLD. IT WOULD BE COOL TO SEE THE MENU OR SOMETHING WHERE WE NOW KNOW IF YOU CHOOSE TO REALLY SUPPORT THIS THING THAT SOMEBODY PRESENTED THERE ARE TRADEOFFS, WHICH I ASSUME THERE ARE. >> SO FIRST YOU SHOULD KNOW, WE HAVE OUR OWN VIEW OF THE WORLD. WE ALL HAVE OUR OWN VIEW OF THE WORLD. AND ONE OF THE MOST IMPORTANT THINGS OUTSIDE OF THE CLOSED SESSION WORK THAT YOU HAVE TO DO YOU CAN DO FOR US IS TELL US EXACTLY WHAT YOU'RE SAYING. WHAT ARE THE ROAD BLOCKS YOU'RE SEEING BECAUSE WE HAVE A PARTICULAR VIEW BUT WE'RE LOOKING AT IT FROM THE INSIDE, AND THAT'S WHY YOU EXIST SO YOU CAN TELL US WHAT WE OUGHT TO WORK ON. AND WHAT YOU'RE SEEING FROM YOUR PERSPECTIVE. AND AS FAR AS ORGANIZING PRINCIPLE, I'M THINKING THE LOGICAL PEOPLE TO DO THIS WOULD BE THE CAN BOARD ACTUALLY. IT'S A SLIGHTLY DIFFERENT QUESTION THAN WE'VE ASKED THE CAN BOARD BEFORE. BUT I CAN'T TELL YOU HOW USEFUL THAT WOULD BE, SO, YEAH, WE WOULD BE ENORMOUSLY ENTHUSIASTIC ABOUT THAT. AND I WANT TO THINK ABOUT THE OTHER QUESTION THAT YOU SAID FOR THE JANUARY MEETING, HOW COULD I PRESENT THIS IN A WAY THAT WOULD BE INTERPRETABLE WITHOUT OVERWHELMING YOU WITH DETAIL AND ACRONYMS, BUT ALL PUBLIC DATA, SO I COULD TELL YOU WHAT THE BUDGETS ARE AND ANNA STARTED DOING THAT WITH HER PIECHART THERE, YOU SAW THE RDR THING. >> THAT WAS HELPFUL. >> YEAH, BUT TO DO IT ON A MORE GLOBAL LEVEL. WHERE DID THE RESOURCES GO? IT WOULD BE A LOGICAL THING TO DO. >> WE TALKED ABOUT HOW WE COULD TELL A STORY OVER TIME TO WHICH NONE OF US WOULD BE, YOU KNOW, AWARE BECAUSE WE'RE NEW. THESE PROJECTS LAST FOR 15 YEARS OR WHATEVER. I THINK MAYBE THE CTSA PROGRAM WOULD BE A GOOD ILLUSTRATION OF THAT POINT BECAUSE IT WAS ONLY A FEW YEARS AGO THAT THE INSTITUTE OF MEDICINE PUBLISHED A REPORT ON THE CTSA PROGRAM, AND THEN WORKING GROUP OF THE NCATS WAS ASSIGNED TO RESPOND TO THAT REPORT. THAT WOULD BE A GOOD STARTING POINT. AND YOU OUTLINED THIS MORNING AS I RECALL A REVIEW OF THE CTSA PROGRAM THAT WE WOULD UNDERTAKE AND THAT WOULD BE A GOOD STORY TO TELL. HERE ARE THE ORIGINS OF THIS. AND MAYBE EVEN GO BACK FURTHER TO WHEN THE CTSA WAS FIRST CREATED, AND THEN THE INSTITUTE OF MEDICINE REPORT, WORKING GROUP RESPONSE, AND THIS NEW UNDERTAKING TO REVIEW THE WHOLE SYSTEM. >> I ALSO WONDER IF WE BECOME MORE EDUCATED, IF THERE'S ANY WAY WE COULD HELP YOU AS A DIRECTOR IN MAKING SOME CHANGE, SO I ALWAYS SAY THIS TO FRANCIS COLLINS, I WAS TAUGHT REAL EARLY AS AN ADVOCATE DON'T GO TO CAPITOL HILL AND PUSH FOR SET ASIDES, LET THE NIH SCIENTISTS DETERMINE WHERE IT SHOULD GO. SOME DECISIONS EVEN THE DIRECTOR COULD WANT TO MAKE BUT POLITICALLY AND FOR OTHER REASONS IT'S IMPOSSIBLE TO MAKE HIMSELF, AN OUTSIDE FORCE LIKE CAPITOL HILL COULD MAKE A DIFFERENCE. THERE MAY BE WAYS WE CAN HELP YOU EFFECT CHANGE THAT ISN'T EASY ON YOUR OWN. >> YOU'RE RIGHT. I REALLY APPRECIATE THAT. IT'S SOMETHING THAT WE'VE TALKED ABOUT A LOT INTERNALLY AND I THINK YOU'LL HEAR MORE FROM US, IT'S SOMETHING YOU MIGHT HEAR ABOUT FROM THE CAN BOARD LEADERSHIP AS WELL. >> ALONG THE LINES OF BRANDING AND MARKETING NCATS IS A POSTER CHILD OF NIH, IT CREATES PLATFORM. THE HISTORY OF THE PROGRAM AND PROJECTS THEMSELVES, ON THE WEBSITE, WOULD BE A BENEFIT BECAUSE IMPACTS CAN CREATE IMPACT METRICS AND THINGS LIKE THAT. IN A SENSE, YOU KNOW, IT'S ABOUT OUTCOMES, ACCOUNTABILITY, AND IN A WAY IT'S ALSO ABOUT CONTINUITY. ACCOUNTABILITY. CONTINUITY. AND THEN YOU BUILD TRUST. TRUST IS A VERY IMPORTANT DRIVER FOR INNOVATION, PARTICULARLY IN HIGH RISK AREAS, SO IT LINKS TO SUCCESS. SO IT'S WORTH TO THINK IT THROUGH AND PERHAPS IMPROVE COMMUNICATION AND TRANSPARENCY. >> HAVING THE STORY WHERE YOU SAY WE PUT X DOLLARS IN, TEN YEARS AGO, AND THIS HAPPENED AND THIS HAPPENED, THIS IS THE ROI, THAT'S AN ARGUMENT FOR YOU TO GET A BIGGER PIECE OF THE BY WHICH GIVES ANNE A BIGGER PIECE OF THE PIE WHICH WE MAKE ME HAPPY, AND IT'S ALL ABOUT ME. [LAUGHTER] BUT ALSO, I THINK THAT THE OTHER MESSAGE THAT NEEDS TO BE GIVEN TO THE OTHER PIE EATERS THAT GET MORE THAN YOU IS THAT YOU SHOULD -- NCATS SHOULD BE REWARDED FOR COLLABORATION, AND IF YOU CAN PROVE AT THE END OF THE DAY COLLABORATION YOU WERE WILLING TO DO X NUMBER OF YEARS AGO OR WHATEVER THE TIMELINE OF THE STORY IS HAS PAID OFF, IF THAT IN TURN GIVES YOU A BIGGER PIECE OF THE PIE IT'S GOING TO SEND A MESSAGE THAT COLLABORATION IS SOMETHING THAT NOT JUST NCATS SHOULD DO. SO I MAY BE POLLYANNA ABOUT HOW YOUR PIE IS GOING TO GET BIGGER. >> THAT'S A GREAT STORY THAT SELLS WELL WHEN CHRIS GOES TO THE HILL TO TESTIFY BEFORE APPROPRIATIONS. >> IF YOU CAN INVEST THIS MUCH, THIS MANY DRUGS CAME OUT OR WHATEVER. I'M SURE YOU ALL TRACK THAT. >> ALL RIGHT. WELL, I'M FEELING GENEROUS TODAY SO I'M GOING TO GIVE YOU FOUR MINUTES BACK. SO THANK YOU ALL. [APPLAUSE] SO DR. MARKS, WE NEED TO UNGAVEL OURSELVES, SO HERE WE GO. ONE, TWO, THREE. ONE MORE TIME. ONE, TWO, THREE. THAT'S BETTER. ALL RIGHT. >> WE'RE ADJOURNED. >> SEE YOU NEXT TIME. SEE YOU ONLINE IN DECEMBER.