THANKS FOR COMING BACK AFTER THE BREAK. WE HAD A LITTLE TIME TO MEET WITH THE SESSION CHAIRS AND THE FOLK WHOSE GAVE THE SUMMARY TALKS AND UPON MY HEAD IT FELL TO SUMMARIZE THE CONFERENCE. THIS CONFERENCE WAS IN PLANNING MORE THAN A YEAR AN HAD PARTICIPATION FROM VARIOUS PARTS OF GOVERNMENT AGENCIES FROM NCATS, THE TREND PROGRAM OR NCPT GROUP AS WELL AS THE FDA AND OTHER INSTITUTES, NINDS, NICHD, REPRESENTATIVES FROM THE NIH CLINICAL CENTER. ALL THESE PEOPLE CONTRIBUTED TREMENDOUSLY TO PULLING IT TOGETHER BUT I WANT TO SINGLE OUT ANDRE P. LAWN HELPED BRING TO FRUITION. I APPRECIATE GOING BACK PLANNING INTO DELIVERY. THANK YOU. I THOUGHT WE WOULD START WITH THOUGHTS FOR SHORT TERM OUTCOMES FOR THE SYMPOSIUM. THERE WAS A VIDEO SIMULCAST FOR THIS SO THE LINK TO THE ARCHIVE VIDEO WILL BE AVAILABLE FOR N DLEAT CATS WEBSITE SHORTLY. WE'RE ALSO GOING TAKE THE SLIDES AN POST ON THE MEETING WEBSITE AVAILABLE FOR THE PUBLIC. IT WON'T BE THE SAME YOU REGISTERED ON. ANYONE ALLOW THEM TO HAVE ACCESS THE WEBSITE WHERE THE SLIDES ARE AVAILABLE. SO NOW THE MORE INTERESTING THOUGHTS. WHAT ARE SOME OF THE LONGER TERM OUTCOMES? IN PREPARING FOR THIS MEETING WE WANTED IT TO BE -- YES WANTED IT TO BE INFORMATIONAL, WE WANTED IT TO CREATE A DIALOGUE AND WE ALSO WANTED SOMETHING TO COME OUT OF IT. MORE SO THAN JUST A GREAT MEETING WHICH IS WHAT I THINK WE HAD OVER THE LAST FEW DAYS. SO YOU ARE THOUGHTS WERE TO COME ONE A WHITE PAPER OR PUBLICATION OF SOME KIND WHERE WE COULD BUILD ON WHAT WE HEARD FROM OVER THE LAST COUPLE OF DAYS WHICH IS TO CLARIFY I THINK THE NEED FOR NATURAL HISTORY STUDIES AN DEVELOP. SO WE LIKE THE WHITE PAPER TO PRESENT THAT CASE AN SHARE BEST PRACTICES AN PITFALLS THAT PEOPLE ENCOUNTERED SO EACH ONE OF THE CASE STUDIES THAT WE HEARD WEIGHED IN ON SOME OF THE THINGS THAT WORK AND SOME THINGS THAT WERE A DISASTER. I THINK IF WE CAN CAPTURE THAT IT WILL BE HELPFUL. AND COMING WITH BEST PRACTICES OR COMMON ELEMENTS TO INCLUDE IN THE STUDIES FOR THE PUBLICATION WILL BE TREMENDOUS. THE NEXT STEP THAT WE CAN DO WOULD BE TO FOLLOW-UP WITH SOME KIND OF PUBLIC CALL FOR INPUT ON ALL THE COMMON CHALLENGES IDENTIFIED OTHER THE COURSE OF THE LAST TWO DAYS. FROM THAT WE HAVE TO THINK OF NEXT STEPS. ONE OF THE NEXT STEPS COULD BE TO PLAN A FOLLOW-UP NATURAL HISTORY MEETING, NATURAL HISTORY STUDY MEETING LIKE THIS BUT FOCUS ON CHALLENGES THAT WE IDENTIFIED FOR THE LAST TWO DAYS. THAT COULD BE VERY EASY FOLLOW-UP. SO I GUESS THE NEXT THING I WOULD LIKE TO SAY IS THIS ISN'T A PRESENTATION WHERE I'M GOING TO TELL YOU EVERYTHING WE LEARNED, THIS IS AN INTERACTIVE DISCUSSION HERE SO IF FOLKS HAVE ANY QUESTIONS OR ANY THOUGHTS ON THIS, I'D APPRECIATE THEM CONTRIBUTING THEM. SO THE QUESTION REALLY FOR PLANING A FOLLOW-UP MEETING WOULD BE WE WOULD LOVE VOLUNTEERS TO PARTICIPATE AND HELP ORGANIZE THIS AND I GUESS SOME INPUT ON WHAT FOLKS THINK WOULD BE A KEY CHALLENGE WE CAN TAKE ON AND TAX ON THE NEXT MEETING. IF WE JUST PLAN A NATURAL HISTORY STUDY MEETING WE WILL COME ONE THE SAME MEETING WE HAD TODAY BECAUSE NOT MUCH WILL CHANGE OVER THE NEXT YEAR BUT IF WE IDENTIFY KEY CHALLENGE AND TACKLE THAT WE'LL COME ONE A MEETING THAT WILL INVOLVE THE GROUP AND THE WAY WE GO ABOUT DOING NATURAL HISTORY STUDIES SO THE COMMON CHALLENGES THAT I THINK WE TALKED ABOUT OVER THE COURSE OF THIS MEETING ARE THINGS LIKE RETENTION OF PATIENTS OR COMMON DATA ELEMENTS, COMMON PATIENT SURVEY FORMS. WE COULD TAKE ANY ONE OF THOSE AND USE THAT AS A TOOL TO DEVELOP ANOTHER MEETING AROUND. SO ONE THING I ASKED THE ORGANIZERS TO DO AS WELL AS FOLKS IF THEY'RE NOT INTERESTED OR DON'T HAVE IDEAS NOW BUT WANT TO CONTRIBUTE SOME IDEAS LATER, THERE WILL BE A LINK FOR COMMENTS AND FEEDBACK ON THE NEW MEETING WEBSITE WITH WITH ALL THE SLIDE INFORMATION SO YOU'LL HAVE THE OPPORTUNITY TO TALK THERE AS WELL. BUT IN THE END WHAT WE WOULD LIKE IS THIS TO BECOME THE START OF ONGOING DIALOGUE IN THIS SPACE WHERE COMMON THEMES THAT CAME ACROSS ARE SOURCES OF FUNDING TO CONTINUE TO DO THESE STUDIES WHICH ARE CRITICAL IMPORTANCE BOTH FOR PATIENTS AND FOR THERAPEUTIC DEVELOPMENT. BUT YET THEY ARE VIEWED AS WHAT'S DOING THERAPEUTIC DEVELOPMENT AND NOT ADEQUATELY RESOURCED. IT WOULD ALSO BE A FANTASTIC OUTCOME TO HAVE A BROADER EMPHASIS ON SHARED RESOURCES AND COMMON TEMPLATES. WE ALSO TALK QUITE A BIT ABOUT TRYING TO HAVE COMMON OR CHANGE THE INCENTIVES FOR THE ACADEMIC COLLABORATORS WORKING ON NATURAL HISTORY STUDIES. SO FOR YOUNG ACADEMICS TO GET INVOLVED IN MULTI-SITE COLLABORATIVE NATURAL HISTORY STUDIES WHEN FUTURE IS DETERMINED OFTEN BY FIRST AUTHORSHIP AND HIGH INSIGHT JOURNALS IS A CHALLENGE. WE TALKED ABOUT THIS QUITE A BIT EVEN A YEAR AGO PLANNING THIS MEETING WE THOUGHT TRYING TO FIND A WAY TO APIPELINE THOSE KIND OF INCENTIVES WITH THE NECESSARY DATA WE NEED TO HELP PATIENTS IS AN IMPORTANT PIECE. I DON'T HAVE ANY QUICK IF I CANS FOR THAT BUT I THINK IT'S CERTAINLY SOMETHING THAT HAS -- THAT BEARS THINKING UPON MOST PATIENT ADVOCACY GROUPS ARE VERY IN TOUCH HOW IMPORTANT BEING AN ACTIVE PARTICIPANT IN THE UNDERSTANDING OF THEIR DISEASE IS AND SO WE I THINK CONTINUING TO GET THAT MESSAGE OUT TO NEWLY FORMED PATIENT GROUPS I THINK WILL BE AN IMPORTANT PART OF THIS ONGOING DIALOGUE WE HOPE TO CREE CRATE FROM THIS MEETING. SO I HAVE OTHER SLIDES BUT I LIKE TO STOP JUST ON THIS ONE FIRST AND SEE WHAT COMMENTS I CAN GET OUT OF THE CROWD HERE. >> SO THERE'S NOT A $20 BILL HERE TODAY. I THINK WE HAVE SEEN GOOD EXAMPLES FOR NATURAL HISTORY STUDIES AND LESSONS LEARNED AND THAT'S GREAT FOR SHARING. I THINK IT WAS CHRIS CHALLENGED US YESTERDAY THAT THERE ARE 7,000 RARE DISEASES, HOW IS THERE A WAY THAT WE CAN TACKLE GROUPS OF THEM OR TO THINK OF HOW TO BUILD INFRASTRUCTURE TO SUPPORT NATURAL HISTORY STUDY THAT PROGRAMS LIKE TREND CAN HELP NOT JUST THE FEW PROJECTS THAT WE'RE WORKING ON YOU TO THE FEEL IN GENERAL. SO WONDER IF THERE ARE THOUGHTS THAT PEOPLE WITH COMMENT NOW OR CAN COME OUT OF THE WHITE PAPERS OR PUBLICATIONS OR AS A TOPIC FOR THE NEXT WORKSHOP. >> SO SEEMS TO ME THERE COULD BE TWO THINGS TO FOCUS AROUND, ONE A FOLLOW-UP TO THAT COMMENT. IT DOES SEEM THAT THERE ARE -- THERE IS A REAL NEED TO HELP SERVICE THE PATIENT ADVOCACY COMMUNITY FOR ALL THE RARE DISEASES THAT ARE OUT THERE. AND HELPING THEM CREATE A FORUM AND I THINK THE NIH IS PROBABLY THE CENTRAL FIGURE THAT IS MOST APPROPRIATELY INVOLVED IN WORKING WITH THE PATIENT ADVOCACY ORGANIZATIONS AND PROVIDING SHARED SERVICES AND I THINK THEY HAVE GOT A START ON THAT. SO HELPING SUPPORT THEM WITH A CONSORTIUM OF EVERYBODY ELSE MUCH LIKE YOU HAVE HERE TODAY. SO I THINK ANOTHER ELEMENT TO THAT, THE SECOND ELEMENT MIGHT BE TO SURVEY THE ACADEMIC AND INDUSTRIAL COMMUNITIES AS TO WHERE DO THEY SEE THE NEXT POSSIBILITY OF GOING WITH THERAPEUTIC ADVANCES. BECAUSE IT'S GOING TO BE ONE THING TO SPEND RESOURCES ON A RARE DISEASE THAT IS A PIE IN THE SKY. ANOTHER THING TO PRIORITIZE THOSE THAT MIGHT BE NEXT INU LINE. FOR THERAPEUTIC ADVANCE WHERE SOMETHING IS ALREADY CONSIDERED AND YOU NEED THE NATURAL HISTORY AS THE LAST PIECE TO TRIGGER US TOWARDS TRIALS. SO PERHAPS A SENSE AND ABILITY TO SURVEY IN THOSE IMMUNITIES TO IDENTIFY MORE LIKELY CANDIDATES WHERE THE NATURAL HISTORY COULD BE ACTED UPON MORE QUICKLY. >> ONE WOULD HOPE THOSE RARE DISEASES THAT ARE QUEUED UP FOR THERAPEUTIC DEVELOPMENT ARE EASIER TO GET CO-FUNDING FOR INDUSTRIAL PARTNERS FOR. SO WITH THAT WE HAVE LONGER TERM OUTCOMES THAT WE TALKED ABOUT. ONE KEY THING IS SOME KIND OF CONSORTIUM OR GUIDANCE OR GROUP THAT COULD PROVIDE GUIDANCE, PERHAPS FUNDING FOR A UNIFIED NATURAL HISTORY DESIGN AND EXECUTION. SO A SOURCE FOR INFORMATION AND GUIDANCE IN DESIGN, WHETHER THIS IS FOR NEW CLINICIANS WHO ARE APPROACHING THE FIRST NATURAL HISTORY STUDY OR PATIENT ADVOCACY GROUPS WHO WANT TO GO DOWN THE ROAD AND DON'T KNOW WHERE TO START. YOU CAN USE THIS -- I'M USING CONSORTIUM LOOSELY. THERE ARE WAYS TO DRIVE THIS AS OUTCOME BUT IT COULD BE A SET OF COMMON TOOLS AN DATA ELEMENTS AND A WAY TO USE EXPAND DATA SETS TO ALLOW BETTER CONTROLS USED IN NATURAL HISTORY AS WELL AS THERAPEUTIC TRIALS. SO IT COULD BE A USEFUL TOOL AND THE WAY TO DO THIS IS TO HAVE EVERYBODY PARTICIPATE AND THERE ARE PARTS NIH HAS TO TAKE THE LEAD ON BUT THERE ARE OTHER PARTS WHERE THIS COULD BE A CLOSE KNIT GROUP TO IMPACT THE WAY THINGS HAVE BEEN GOING FORWARD. I WAS STRUCK BY DR. GALLIN'S REQUEST FOR RARE DISEASE ATLAS. HE STARTED THE MEETING OFF WITH THAT AS WHAT HIS VISION WAS. IF YOU THINK ABOUT HAVING A MUCH BETTER UNDERSTANDING FROM NATURAL HISTORY STUDIES OF A RANGE OF RARE DISEASES YOU CAN BUILD BASED ON INFORMATION THAT MIGHT BE COLLECTED AND POOLED IN CONSORTIUM. THE KEY THING WE HEARD ABOUT ARE COMMON DATA ELEMENTS OR EVEN BETTER DEFINITIONS OF CLINICAL TERMS PEOPLE USE IN SURVEYS OR CHART REVIEWS COULD BE BENEFICIAL IN TERMS OF ALLOWING FUTURE NATURAL HISTORY STUDIES TO GO FORE. SO AGAIN, IF ANYBODY HAS ANY INSIGHTS ON HOW TO PUT TOGETHER SOME GROUPS THAT COULD ADDRESS ISSUES I WOULD LOVE TO HEAR ABOUT IT. SO THESE REALLY ARE THE THREE SLIDES I PUT TOGETHER TO THINK ABOUT POTENTIAL OUTCOMES AND HOW TO GO FORWARD. THE OTHER SLIDES ARE REALLY A SUMMARY OF SOME OF IDEAS AND CHALLENGES THAT WE HAVE TALKED ABOUT OVER THE LAST COUPLE OF DAYS. SO I'LL GO THROUGH THOSE AND MAYBE COME BACK TO THESE OUTCOMES AS YOU HAVE HAD A CHANCE TO THINK ABOUT THEM A LITTLE BIT. BUT I THINK WE HER A VERY IMPASSION SET OF TALKS ABOUT HOW IMPORTANT THE ROLE OF NATURAL HISTORY STUDIES ARE, THE FACT THEY'RE ESSENTIAL TO THERAPEUTIC DEVELOPMENT AND REALLY WHEN WE SAY THAT WHAT WE'RE REALLY MEANING IS THEY'RE GOING TO FACILITATE DRUG DEVELOPMENT AND FACILITATE CLINICAL CARE AND THOSE WILL BE BENEFICIAL FOR EVERYONE INVOLVED. WE SAW A NUMBER OF CASES WHERE AFTER THOROUGH NATURAL HISTORY STUDY WAS DONE, PATIENT OUTCOMES CHANGED DRAMATICALLY WITHOUT WITH DEVELOPMENT OF THERAPEUTIC. SO I THINK THE DATA FOR CYSTIC FIBROSIS IN ANN'S TALK WAS MOST RELEVANT BUT MARSHALL SUMMER ALSO PRESENTED THAT FOR HIS SERIES CYCLE DISORDERS, THERE ARE AT LEAST TWO WHERE SURVIVAL RATES WHERE HIGHER THAN THEY SHAIIVE BASED ON HISTORICAL DATA. THE -- KEY ROLE IS TO IDENTIFY GUIDELINES AN BIOMARKERS TO DEVELOP DIAGNOSTICS THAT WILL IDENTIFY YOUR PATIENT POPULATIONS GOING FORWARD. BUT MOST IMPORTANTLY, YOU DON'T GET MANY CHANCES AT THERAPEUTIC DEVELOPMENT. UNDERSTANDING THE DISEASE RARE DISEASE WHERE IS THEY'RE SMALL PATIENT POPULATIONS YOU HAVE TO SEIZE THAT ONE TIME AND DO IT WELL. ANN MADE A VERY GOOD POINT HOW OFTEN FOR MANY RARE DISEASE THERE'S NO REGULATORY PATHWAY TO FOLLOW. SO HAVING A NATURAL HISTORY STUDY TO SUPPORT THAT PIECE, HELP YOU DEVELOP A REGULATORY PATHWAY BASEDDEN THOROUGH KNOWLEDGE OF THE DISEASE IS REALLY IMPORTANT. THEN AGAIN, THERE WERE MULTIPLE EXAMPLES OF WHY IT'S IMPORTANT a NATURAL HISTORY OF DISEASE AFTER THERAPEUTIC DWOM. YOU HEARD ABOUT (INDISCERNIBLE) WHERE THERE ARE MULTIPLE FACETS OF THESE DISEASES BEING UNVEILED AFTER THERAPEUTICS DEVELOPED TO ALLOW YOU TO SEE THEM SO THE ROLL IS DEFINEDDED OVER THE COURSE OF LAST TWO DAYS. THE BENEFITS OF A STUDY LIKE THIS ARE EVERYBODY BENEFITS. IT'S EASY THE MAKE THIS A WIN WIN, I THINK FOR BOTH RESEARCHERS INVOLVED AND PATIENTS AND CAREGIVERS. THERE ARE A LOT OF COMMENTS HAVING -- THIS IS A LOCK TERM COMMITMENT TO WORK TOGETHER SO YOU DO HAVE TO CHOOSE WHO YOU'RE GOING TO WORK WITH. ONCE THE RELATIONSHIP IS BUILT IT BEHOOFIOUS TO NURTURE BECAUSE BOTH SIDES GET QUITE A BIT OUT OF IT. THE ACTIVE ENGAGEMENT OF RARE DISEASE COMMUNITY, THE PATIENT BENEFITS FUTURE DEVELOPMENT. THE KEY THINGS IN KEEPING THAT RELATIONSHIP POSITIVE IS BEING REALISTIC ABOUT H YOU EXPECT YOUR PATIENTS TO DO AND AMOUNT OF DATA GENERATE IN A SINGLE DAY FROM THEM AND ANYTHING YOU CAN DO TO MAKE EASIER ON THE PATIENTS YOU WILL HAVE THIS LONG TERM COMMITMENT. INDIVIDUAL EFFORTS MULTIPLE INDIVIDUAL EFFORTS ARE -- TEND TO BE COUNTER PRODUCTIVE GETTING ONE LARGE NATURAL HISTORY STUDY WITH CONTRIBUTORS IS A BETTER WAY TO GO FORE. ANOTHER THEM THAT CAME ACROSS AS POTENTIAL BENEFIT IS THAT A NATURAL HISTORY STUDY COUPLED WITH OR NOT A DISEASE SPECIFICALLY IN THIS CASE CREATE AS MEDICAL HOME FOR PATIENTS WITH RARE DISEASE. A GROUP OF PATIENT CARE PROVIDERS THEY CAN TURN TO FOR ALL THEIR QUESTIONS. THEN BROADLY INDUSTRY NEEDS THIS DATA IN ORDER TO PLAN FOR THE THERAPEUTIC DEVELOPMENT THERE IS A LOT FOR COMPANIES PLANNING THERAPEUTIC DEVELOPMENT AND IN TERMS OF FDA IF YOU HAVE A SOLID NL HISTORY STUDY YOU CAN START THE IDENTIFY WHAT POPULATIONS YOUR THERAPEUTIC MAY WORK IN WILL MAKE EVERYTHING EASIER. GENERAL PRINCIPLES YOU SHOULD START BY THINKING ABOUT WHRERNING ABOUT THE DISEASE AND NOT THERAPEUTIC SPECIFIC IN YOUR CE SIGN. EVERYBODY MENTIONED THAT CONSIDERING THESE NATURAL HISTORY STUDIES TO BE PRE-COMPETITIVE SPACE MAKE IT IS MOST SENSE. EVERYBODY ALSO SAID STARTING WITH TEND IN MIND IS THE WAY TO DO IT SO YOU HAVE TO HAVE THOUGHT WHAT A THERAPEUTIC DEVELOPMENT PLAN MIGHT BE IN ORDER TO ENABLE YOU TO COLLECT ENOUGH DATA TO REALLY BENEFIT BROAD RANGE OF PARTNERS. IT IS USEFUL TO KEEP IN MIND THESE ARE MUT YEAR STUDIES THAT TEND TO EVOLVE OVER TIME. IT IS NOT A FIXED PROTOCOL, YOU HAVE TO REACT TO THE DATA YOU'RE GENERATING. MULTIPLE AREAS OF BIAS CREEP INTO NATURAL HISTORY STUDY DATA AND WE HEARD MANY EXAMPLES FROM RETENTION RATES FOCUSING IN ON YOUR SICK POPULATION OR OTHER EXAMPLES WHERE NEWER INVESTIGATORS INTO ONGOING TRIAL HAD ACCESS TO RESULTS THAT MIGHT IMPACT INTERPRETING DATA. KEY THOUGHTS TO HAVE FOR SUCCESSFUL PARTICULARLY COLLABORATIVE NATURAL HISTORY STUDY ARE NEGOTIATE DATA ACCESS AN PUBLICATION RIGHTS EARLY SO EVERYBODY UNDERSTANDS WHAT THEY GIVE TO THIS COALITION AND WHAT THEY CAN EXPECT IN TRURN. ITALSO IMPORTANT PO TO POINT OUT HAVING A PLAN TO CLOSE OUT SITES THAT CAN'T BRING IN PATIENTS FOR THEM TO SCREN RATE HIGH QUALITY DATA IS AN IMPORTANT PIECE THAT ENABLE YOU TO BRING IN NEW ONES TO FILL THAT NEED. THE ONE OTHER CLEAR THING THAT CAME THROUGH WAS TRYING TO COMBINE RESEARCH IN CLINICAL VISITS ON THE SAME DAY. TO MAKE A DELINEATION BETWEEN THE TWO AND WHO GETS BILLED AND HOW BUT TRYING TO MAKE YOUR PATIENTS LIVES EASIER BY COMING ONE DAY INSTEAD OF MULTIPLE TRIPS MAKES A BIG DIFFERENCE. A GOOD DATA COORDINATOR SOMEBODY EVERYBODY RAVED SO IMPORTANT Z YOU KEEP THIS IN MINE. YOU WANT TO AVOID MISSION A FATIGUE BY HAVING TOO MANY MEETINGS, HAVING JUST ENOUGH TO KEEP EVERYBODY INTERESTED AND CONTRIBUTING. IS THERE WERE DISCUSSIONS AB SITE DECISIONS WHETHER TO HAVE A SINGLE OR MULTIPLE SITE AS PART OF YOUR STUDY. SO IN TERMS OF YOU GO FORWARD WITH TRIALS YOU SHOULD KEEP THESE IN MIND. SINGLE SITE GIVES YOU SOME ADVANTAGES IN TERMS OF HAVING THE SAME GROUP OF EXPERTS DO THE ASSESSMENTS AN YOU HAVE GOOD DATA QUALITY AN CONTROL YOU CAN DRIVE FROM A SINGLE SITE. BUT TOUGH HAVE PATIENT TRAVEL OR RELY ON A SMALL GEOGRAPHIC DRAW. FOR MULTIPLE SITES YOU HAVE ASSESSMENTS OF CONTINUOUS TRAINING TO BECOME ESSENTIAL TO GET DATA TO IM HIGH QUALITY BUT YOU ALSO HAVE ISSUES OF MULTIPLE IRB APPROVAL. WHICH SURPRISE ME THE EXOF LARGE TIME AND INVESTMENT REQUIRED. UPWARDS OF TWO YEARS WAS ONE OF THE TALKS WE HEARD TO GET 15 OR 19 SITES INVOLVED. SO ONE OF THE KEY THINGS THAT I THINK WOULD BE VERY USEFUL GOING FORWARD, DEVELOP A CENTRAL IRB PROTOCOL MUCH LIKE NEURONEXT TO ACCELERATE THE MULTI-SITE NATURAL HISTORY STUDIES. I THINK THERE'S THIS WILL EVOLVE OVER TIME WHEN NEURONEXT CAN SHOW EXAMPLES HOW MUCH TIME THEY SAVE BY HAVING CENTRAL IRB OR OTHER PROTOCOLS BUT THIS WILL BE A SLOWLY PROGRESSING IDEAL WE'LL WORK TOWARD. I WANT TO ALSO GIVE A SNAP SHOT OF THE STUDY OPTIONS. WE HEARD ABOUT CHART REVIEWS A LITTLE BIT ABOUT LITERATURE REVIEWS AND A LOT OF PERSPECTIVE CROSS SECTIONAL STUDIES WHICH START WITH PATIENT SURVEYS AND THEN LONGER LONGITUDINAL STUDIES PEOPLE PRESENTED. IT'S IMPORTANT NOT TO JUST CHOOSE ONE, YOU HAVE TO USE A COME TBHAITION. PATIENT SURVEYS, CHART REVIEW, PLAN WHAT YOU LOOK FOR AND WHAT DATA YOU COLLECT AND EVOLVE DOWN THIS LIST OF STUDY OPTIONS. THERE IS TRADE OFF IN TERMS OF TIME REQUIRED VERSUS RICHNESS OF THE DATA PACKAGE. THE HIGHLIGHT IS GOING TO BE PERSPECTIVE LONGITUDINAL STUDY BUT IT MAY TAKE 12 YEARS TO GET ENOUGH DATA TO THINK -- LOOK INTO THE DATA DEEPLY ENOUGH TO LEARN THINGS. APPROACHING YOUR APPROACHING THE DATA COLLECTION YOU'RE GOING TO DO CAN CHANGE OVER THE TIME THAT YOU'RE LOOKING AT THINGS. SO THAT WAS MY SUMMARY OF THE LAST TWO DAYS OF CHALLENGES AND NATURAL HISTORY STUDIES. SO I THINK GOING BACK TO SOME OF THE OUTP COMES YOU HAVE HAD A COUPLE OF MINUTES TO THINK ABOUT THESE AND I WOULD LOVE MORE INSIGHTS. WE WELCOME THOUGHTS AND PARTICIPANTS TO EMAIL BACK BUT NOW IS A GREAT TIME TO GET YOUR VIEWPOINTS HEARD. >> ONE THING THAT I THINK KEPT ON COMING UP IS WITH CERTAINLY WITH FOUNDATIONS TRYING TO START A REGISTRY AN NEW DISEASE, FLUORINE WAS A GOOD EXAMPLE FOR THE FIRST TIME TRYING TO DEVELOP A PROGRAM. I THINK EVEN HAVING A COMPENDIUM OF THE VARIOUS REGISTRIES, THAT PEOPLE LOOK AT WHAT'S DONE BEFORE, CONTACT PEOPLE, AND I THINK WHAT WILL HAPPEN IS THAT WITH MORE AND MORE REGISTRIES WE'LL HAVE AN APPRECIATION OF WHAT WORKS AND WHAT DOESN'T. BEING ABLE TO ADDRESS RAREIOUS DIFFERENT ORGAN SYSTEMS. SO THERE MAYBE A SET OF QUESTIONS OR THINGS IMPERATIVE FOR SKELETAL DISEASE LIKE MPS-1 OR PERIPHERAL NERVOUS SYSTEM DISEASE. SO HAVING SOME OF THESE QUESTIONS AND NATURAL HISTORY PARAMETERS THAT ARE BEING COLLECTED, JUST TO BE ABLE TO LOOK AT WHAT'S ALREADY THERE AND WHAT MIGHT FIT IN YOUR DISEASE, SO SOMEONE DOES HAVEN'T TO START FROM SCRATCH, IT MUST BE INTIMIDATING AND I HEARD PEOPLE ASKING FOR HELP. I KNOW IT'S IMPORTANT BUT WHERE DO I START. HAVING EXAMPLES OVER TIME HAVING PEOPLE, IT PROBABLY NEEDS TO BE A DIVERSE POPULATION BECAUSE EVEN IN DISEASE LIKE LYSESOMAL STORAGE DISEASE THEY AFFECT MANY ORGANS. NOT ALL QUESTIONS AN OUTCOME MEASURES ARE CAPTURED. IT IS LIKE A SHELF. YOU TAKE SOME HERE AND MIX IT UP AND HAVE YOUR OWN PERSONALIZED REGISTRY FOR YOUR DISEASE. THEN IT GETS TO THE COMMON ELEMENTS SO JUST STARTING WITH A COMPENDIUM, IT SHOULD BE INTERNATIONAL BECAUSE PEOPLE SHOULDN'T BE DOING SOMETHING IN THE U.S. AND SOMEBODY ELSE ALREADY DONE IT IN EUROPE. IS THERE NEEDS FOB A I -- THERE NEEDS TO BE A WAY TO COLLABORATE AND DO A BETTER JOB. >> I WAS GOING TO MAKE A POINT ABOUT DIFFERENT DOMAINS THAT WE'RE TALKING ABOUT. RARE DISEASE GROUP, I THINK GLOSSED OVER THAT A LITTLE BIT, REALLY IT'S NEEDING ALL THIS EXPERTS LOOKING AT THE WORLD DIFFERENTLY AND NEURORL GISTS AN GENETICISTS THINKING DIFFERENT DOMAINS AND HOW TO BRING THAT LANGUAGE TOGETHER I THINK WILL BE A CHALLENGE IF YOU'RE TRYING TO COME UP WITH SOME UNIFIED GUIDELINES. THE OTHER WAY TO LOOK AT IT WOULD BE TO SEE IF YOU CAN COLLECT EXPERIENCE PITFALLS. FDA HAS A COLLECTION OF PITFALLS AN NATURAL HISTORY STUDIES DONE AND COULD YOU GAIN SOMETHING FROM THAT AND LOOK AT THE WORLD FROM UPSIDE DOWN AND SAY THIS IS WHAT WE DON'T WANT TO HAVE HAPPEN. JUST SOME THOUGHTS. >> HEATHER ADAMS FROM THE UNIVERSITY OF ROCHESTER. THIS IS A FOLLOW-UP ON MY QUESTION FROM YESTERDAY. I THINK THAT ANYONE WHO IS DEVELOPING NATURAL HISTORY RESEARCH CERTAINLY INVOLVES FROM THE BEGINNING AS PLAN HOW TO WORK WITH DATA ONCE THEY GET IT BUT IT CAN'T BE EMPHASIZED ENOUGH HOW IMPORTANT IT IS TO THINK ABOUT HOW TO APPROACH YOUR DATA FROM START OF WHEN QUESTIONS ARE WRITTEN. THE WAY INSTRUMENTS ARE SCALED, THE MEASURE, ASSESSMENTS OF SYMPTOMS OF CLINICAL FUNCTION, QUALITY OF LIFE, ARE CAPTURED ARE GOING TO INFLUENCE THE STATISTICAL PROPERTIES OF THAT SCALE, INFLUENCE THE KIND OF INFORMATION YOU CAN PULL LATER WHEN LOOKING AT YOUR DATA AND LONG TERM. SO I BRING THIS UP BECAUSE IT'S AN AREA I KNOW, SOMETHING THAT I RELY UPON, OUR STATISTICAL EXPERTS FOR HELP WITH. SO I'M ALWAYS LOOKING FOR OPPORTUNITIES TO LEARN MORE ABOUT THAT. I THINK THAT THAT'S SOMETHING THAT AS WE LOOK AT FUTURE MEETINGS MIGHT BE A TOPIC TO CONSIDER, HOW WE ACTUALLY DO SCALE DEVELOPMENT. HOW WE DO IT IN A WAY THAT WILL PROMOTE GOOD DATA LATER ON. THAT'S BASICALLY WHAT I WANTED TO SAY. THANK YOU. >> WALTER KAUFMAN FROM CHILDREN'S HOSPITAL BOSTON. LOOKING AT THE FUTURE AND LOOKING FORWARD I THINK THAT OUR NATURAL HISTORY STUDY OF RHETTs SYNDROME IS A GOOD EXAMPLE OF SUCCESSFUL ENTERPRISE BUT OUR UNCERTAINTIES AN CHALLENGES ARE SEEN IN THE REFLECTION OF WHAT IS NEEDED IN THE FIELD. WE'RE ABOUT FUNDING. WE HAVE A SYSTEM THAT IS A MULTI-SITE MIX SYSTEM WHICH IS I THINK A REMARKABLE THING THAT WAS DEVELOPED BY (INDISCERNIBLE) THE PI WHICH WE HAVE FOUR SITES THAT WORK TOGETHER, BUT IN ADDITION TO THAT WE HAVE TRAVELING CLINICS. WE GO TO OTHER FOUR SITES THROUGHOUT THE U.S. WITH THE FOUR PERMANENT SITE GO AND PARTICIPATE AND WE SHARE OR DIVIDE A NUMBER OF PATIENTS TO BE SEEN DURING THE COURSE OF A WEEKEND. (INAUDIBLE) TOGETHER TO DISCUSS WHAT WE'RE DOING, WE'RE AT THE SAME SITE. WE DON'T HAVE TO GO TO THE OTHER PERMANENT SITE BUT WE DO IN THIS INTERMEDIATE LOCATION. THAT'S NOT FUNDED BY THE NIH, FUNDED BY INTERNATIONAL (INAUDIBLE) FOUNDATION AND IT IS A MAJOR UNDERTAKING IN THE ADVOCACY GROUP IN CHICAGO, MIDWEST T LOCAL GROUP BRINGS PATIENTS FROM ALL OVER THE MIDWEST. AGAIN, THE QUESTION IS HOW MUCH ARE WE GOING TO BE SUPPORTED BY THE FOUNDATION AS WELL AS BY NIH. SO THAT'S ONE OF THE ANXIETIES. THE SECOND IS INTELLECTUAL RESOURCES. SO OBVIOUSLY WE ARE LOOKING AT THE SAME THING MENTIONED OVER THE COURSE OF TWO DAYS, DEVELOP DIAGNOSTIC MARKERS. DEVELOPING OUTCOME MEASURES. AND OF COURSE WE ARE A VERY COHESIVE COMMUNITY SO WE TALK WITH EVERYONE WHO NOSE RHETT SYNDROME, WE NEED DIFFERENT -- SO HAVING A CENTRAL PLACE TO GO, WEBSITE, COMMUNITY OF EXPERTS TO GO FOR THE NEXT STEPS IS EXTREMELY VALUABLE. THE NEXT STEPS IS NOT ONLY DIAGNOSTIC AND BIOMARKERS AND OUTCOME MEASURES BUT ALSO WHAT JEFF ANNUAL MENTIONED YESTERDAY ABOUT NEWBORN SCREENING OR GENETIC SCREENING WHICH IS IMPORTANT IN DISORDER MAYBE FOR A NUMBER OF DISORDERS SO IN SUMMARY, WE HAVE THE FINANCIAL BASE OF SUPPORT TO CONTINUE FORWARD INTELLECTUAL RESOURCES, WE DON'T WASTE TIME TRYING TO REINVENT THE WHEEL, WE WILL BE SUCCESSFUL IN THE LONG RUN. >> LARRY CHARNESS SHIRE. I'M GOING TO COMMENT ON REINVENTING THE WHEEL AND WONDERING ABOUT BREAKING DOWN SILOS WITHIN THE NATIONAL INSTITUTES OF HEALTH. THE NEWBORN SCREENING PROGRAM HAS GOTTEN A LARGE GRANT FROM NICHD, MANY ISSUES HAVE ALREADY BEEN ADDRESSED, THEY HAVE A PAM OF DISEASES, ALMOST ALL OF WHICH ARE RARE. THEY WANT TO LEARN SOMETHING ABOUT THE LONG TERM FOLLOW-UP AND HOW THEY HAVE DN THAT, THEY CREATE A TEMPLATE FOR THE DESCRIPTION OF THE DISEASE AND DATA HE WILLN'TS THEY WANT TO LOOK AT. SEEMS MANY OF THE QUESTIONS HAVE BEEN ADDRESSED BY ANOTHER NIH FUNDED GROUP AND BRINGING THIS TOGETHER SO THAT PEOPLE8 ALIGNED AND USING THE SAME COMMON DATA ELEMENTS WOULD BE HEALTH. -- HELPFUL. >> THIS IS (INAUDIBLE) FROM FDA. I WANT TO SHARE ONE OF THE MANY THINGS I HAVE LEARNED FOR THE PAST ONE AND A HALF DAYS. WHICH IS THE STATISTICAL CONSIDERATION IN TERMS OF THE DESIGN AND THE CONDUCTION OF NATURAL HISTORY STUDY. THIS IS AT LEAST SOMETHING THAT I PERSONALLY HAVE NOT SUCH REALLY THOUGHT ABOUT A LOT. WHEN WE TALK ABOUT CLINICAL TRIALS THERE'S SO MANY CLINICAL TRIAL DESIGNS, SO MANY CLINICAL STATISTICAL CONSIDERATIONS AND WE HAVE ALL THE DESIGN, HOWEVER I NOTICE WHEN WE TALK ABOUT NATURAL HISTORY STUDIES DESIGNS, WE START THE STATISTICAL CONSIDERATION IS SORT OF IN THE BACKGROUND. I THINK IT WILL BE REALLY HELPFUL IF WE COULD UTILIZE MORE IN TERMS OF ANALYZE THE CROSS SECTIONAL DATA, THE RETROSPECTIVE CHART REVIEWS AND ALSO IN TERMS OF DESIGNS LONG TERM EXPENSIVE PROSPECTIVE LONGITUDINAL STUDIES AND I THINK IT WILL BE SOMETHING REALLY SOMETHING TO THINK ABOUT. >> TWO THINGS. ONE TO ECHO WHAT I HER, THIS SHOULD BE MORE INTERNATIONAL GROUP, IN TERMS OF THE REGULAR LA REQUIREMENTS, THE FDA DOES THINGS ONE WAY BUT FOR EXAMPLE IN THE EUROPEAN UNION THEY HAVE DIFFERENT CRITERIA. SO IN TERMS OF WIDENING THE MARKET AND ALSO TREATING MORE PATIENTS I THINK WE SHOULD BE BRINGING IN THESE FOLKS TO HELP US DESIGN THE BEST NATURAL HISTORY STUDIES SO THE DATA WE COLLECT WILL BE USEFUL FOR ALL MARKETS IN THE END. SECOND THING I WANT TO POINT ALSO REITERATE WAS THE PREVIOUS SPEAKER TALKING STATISTICS. YOU CAN INCREASE THE POWER OF YOUR TRIAL BASED ON THE OUTCOME MEASURE. THIS WAS SOME OF THE -- SOMEBODY PRESENTED YESTERDAY. LOOKING AT SURVIVAL IS WONDERFUL, BUT THAT IS AN INFORMATION POOR ENPOINT SO YOU NEED MORE PATIENTS TO GET TO SEE SOME STATISTICAL SIGNIFICANCE SO WE NEED TO THINK ABOUT WHAT END POINTS IN TERMS OF RATE OF CHANGE, THAT KIND OF THING COULD BRING POWER TO STUDIES WITH FEWER PATIENTS. >> STEVE GROFIT OFFICE OF RARE DISEASE RESEARCH. I DID WANT TO MENTION THE FOCUS OF THE MEETING WAS ON NATURAL HISTORY STUDIES. WHAT WE DIDN'T REALLY TALK ABOUT TOO MUCH IN PREPARATION WAS ALL THE PLANNING AND THE WORK THAT IS ONGOING FOR THE VARIOUS PATIENT REGISTRIES, I DO WANT TO INDICATE TO EVERYONE HERE THERE HAVE BEEN CONSIDERABLE EFFORTS WE HAVE HEARD SEEING THE MANY EFFORTS NINDS THAT THEY HAVE TAKEN TO DEVELOP THE DATA ELEMENTS FOR MANY NEUROLOGICAL DISORDERS AND THEY WILL CONTINUE TO DO THIS. SEVERAL INSTITUTES ARE FOLLOWING THE SAME PATTERN. WE IN THE OFFICE ARE WORKING WITH NUMEROUS INSTITUTES TO COME UP WITH THOSE DATA ELEMENTS. AND I THINK THIS IS JUST THE PATIENT REGISTRY IS PART OF THE CONTINUUM THAT WE SEE TO MOVE THE RESEARCH, MOVE THE DEVELOPMENT OF INFORMATION INTO THE STAGE WHERE WE'RE READY TO DEVELOP PRODUCTS. SO WE DO HAVE SOME PLANS AND CONSISTENCY. WE'RE WORKING VERY CLOSELY WITH THE EUROPEAN UNION FOLKS, A GROUP HAS JUST BEEN OR IN THE PROCESS OF RECEIVING A GRANT FROM THE EUROPEAN COMMISSION TO DO SIMILAR WORK TO WHAT WE HAVE BEEN DOING, WE HAVE BEEN IN TOUCH WITH THEM FOR SEVERAL YEARS WORKING WITH THEM FOR THIS CONSISTENCY AND STANDARDIZATION. AHRQ, AGENCY FOR HEALTHCARE RESEARCH AND CALL ARE IN THE PROCESS OF DEVELOPING A REGISTRY OF PATIENT REGISTRIES SO THAT IS IN THE WORKS. AGAIN, COMMUNICATIONS ARE THERE, I THINK WHERE WE RUN INTO ISSUES ARE THE PLAYERS ARE WE ABLE TO KEEP EVERYONE TOGETHER TO THINK IN COMMON TERMS AND DIRECTION THAT WE CAN MAINTAIN, THE CONSISTENCY OF WHAT MANY OF US FEEL IS WjTT::p)Y IF WE'RE GOING TO HAVE RESEARCH MOVING FORWARD IN A SYSTEMATIC WAY. SO I THINK WE ARE MOVING IN THAT DIRECTION, IT IS A TIME FACTOR, I THINK SOME FUNDS HAVE BEEN ALLOCATED FOR A NUMBER OF PROJECTS WE HAVE WILL SOON ANNOUNCE THE FIRST GROUP OF INDIVIDUAL ORGANIZATIONS THAT WE'LL BE WORKING WITH DEVELOPING REGISTRIES AN THEM PLAYS AND MANY OTHER ACTIVITIES THAT ARE FORTHCOMING SO I THINK WE WILL BE SHARING THAT WITH EVERYONE. WHAT WILL BE ESSENTIAL MOVING FORWARD, JOHN MADE REFERENCE TO THIS, DEVELOPING THE WORKING GROUPS THAT WILL TAKE SEPARATE PARTS AND BRING THEM TOGETHER SO WE CAN THEN HAVE EVERYONE BECOME ORGANIZED AND MOVE THE ENTIRE PROCESS FORWARD. WHAT I HAVE BEEN HEARING AT THE MEETING, THERE ARE CERTAINLY A NUMBER OF PARTNERS WILLING TO DO SO. WE'RE REI DO GO, JUST MAINTAIN THAT ENERGY AS WE LEAF THE MEETING SO TOMORROW WE HAVE THAT SAME ENERGY AND MAKE THAT COMMITMENT TO MOVE FORWARD. SO I THINK WE'RE IN GOOD SHAPE. FUNDS IS ALWAYS AN ISSUE.KF– AS INDUSTRY FINDS FUNDS FOR DIFFERENT THINGIOUS NEED. THE PATIENT WE HAVE HAD WONDERFUL WORKING RELATIONSHIP WITH FDA NOT JUST THIS ISSUE BUT MANY ISSUES IN REGULATORY AND INDUSTRY AN PATIENT ADVOCACY GROUPS SO WE HAVE TO MAINTAIN THAT MOMENTUM. I THINK WE'LL CONTINUE IT AND COME UP WITH SOME NICE FINISHED PRODUCTS AN GOOD GUIDANCE FOR THE FOLKS WHO NEED THIS MOVING FORWARD. >>, SO AT THE RISK OF BEATING A DEAD HORSE I WILL BEAT A DEAD HORSE. THERE ARE A FEW PATIENTS GROUPS HERE SO I'M SPEAKING FOR THE OTHER PATIENT GROWTH BRETHREN WHO CAN'T AFFORD TO GET TO THESE MEETINGS. TAKE ADVANTAGE OF US. WE'RE DESPERATE. WE ARE WORRIED FOR OUR CHILDREN'S LIVES, OR OUR SPOUSES OR PARENTS. AND IT MAYBE YEARS OR DECADES BEFORE THERE ARE CLINICAL TRIALS. BUT WE NEED TO BE KEPT BUSY AND WE NEED TO FEEL LIKE WE'RE MAKING A DIFFERENCE IN OUR FAMILIES LIVES SO GIVE US OUR HOME WORK. MY 8TH GREATER GETS AN ASSIGNMENT FOR THE SCIENCE FAIR PROJECT HE HAS A RUBRIC, HE HAS TO DO CERTAIN THINGS AT CERTAIN TIMES AND HE GETS SCORED. THAT'S WHAT THE FDA DOES, THEY TELL US WHAT WE HAVE TO DO, WE GET SCORED AND YOU EITHER MAKE IT OR YOU DON'T. WE'RE NOT ALLSIS SICK FIBROSIS. SOME OF US ARE A BUNCH OF MOMS OR SPOUSES WHO DIDN'T TAKE SCIENCE BECAUSE THEY DIDN'T LIKE IT. IF YOU WANT US TO DO THIS RIGHT WITHOUT MONEY TEACH US HOW YOU WANT IT DONE. AND THROW US A FEW BUCKS EVERY ONCE IN A WHILE. I TOTALLY GET THE POINT WITH THE DIFFERENT NIHSLY LEAVE TO IT Y'ALL TO GET IT OUT. BUT REINVENTING THE WHEEL IS CRAZY. OUR GROUP IS FORTUNATE ENOUGH TO GO THE GROUPS LIKE AUTISM SPEAKS OR FRAGILE X OR DUSHEN FOR GUIDANCE. BUT WITH THE ONSET OF GENETIC DIAGNOSES, WE'RE ON THE CUSP OF MORE DISEASES COMING FORWARD. AND I THINK SOMEBODY NEEDS TO STOP AND GIVE THESE LITTLE TINY DISEASES THESE 20 TO 2,000 MEMBER DISEASES A DESCRIPTION OF WHAT NEEDS TO BE DONE. FIRST 301C THEN REGISTRY THAT'S NOT JUST AN ADDRESS BOOK BY THE WAY, YOU CAN COLLECT A LOT OF VALUABLE INFORMATION IN A PATIENT GROUP. THEN YOU DO A NATURAL HISTORY. THESE ARE THE CONSEQUENCES IF YOU DON'T DO THESE THINGS. THIS IS WHY YOU HAVE TO DO THEM IN ORDER. IF YOU WANT US TO DO THE STUFF BEFORE CLINICAL TRIALS, SHOW US HOW TO DO IT. SET UP PILOT PROGRAMS AND WHOEVER GETS THE MONEY FROM NIH HAS TO BE MENTORS TO OTHER DISEASE GROUPS. I SET UP A REGISTRIEN OUR OWN, WE PAID FOR IT OURSELVES BECAUSE WE WESTERN WILLING TO WAIT FOR ORDR TO GET WHERE THEY ARE TODAY. I WILL ANSWER ANY QUESTIONS TO ANY PATIENT GROUP. I THINK WE NEED A LITTLE BIT MORE GUIDANCE FROM Y'ALL AND Y'ALL ARE TOTALLY UNDERESTIMATING WHAT WE CAN DO. I'M HAPPY TO SUGGEST ANY OTHER GROUPS THAT MIGHT BE HELPFUL FOR NEXT YEAR'S MEETING. [APPLAUSE] >> MAKE SURE WE KNOW WHAT YOUR NAME IS BECAUSE YOU JUST GOT YOURSELF ON THE IMPLEMENTATION GROUP. I'M SERIOUS. SO CHRIS AUSTIN, I TRUN DIVISION OF PRE-CLINICAL INNOVATION AT NCATS, I WANT TO SAY A FEW THINGS. THE FIRST IS WOW. I HAVE BEEN SITTING DOWN HERE THE LAST TWO DAYS. I HAVE HIGH EXPECTATIONS FOR THIS MEETING BUT ACTUALLY THE EXPECTATIONS MY EXPECTATIONS HAVE BEEN TOTALLY BLOWN AWAY BY THE PASSION, YOU HEARD A GREAT EXAMPLE OF THAT, THE KNOWLEDGE THE INFORMATIVE NATURE OF THE PRESENTATIONS. AND THE WILLINGNESS TO WORK TOGETHER. SO JUST HAD A COUPLE OF THOUGHTS, THREE PERHAPS. ONE IS ABOUT OPPORTUNITY, ONE IS PRECEDENT AND ONE IS ABOUT IMPLEMENTATION. AS FAR AS THE OPPORTUNITY IS CONCERNED, I THINK WHAT I HAVE HEARD AND WHAT IS HAPPENING THAT YOU MAY NOT BE AWARE OF THERE,' ENORMOUS OPPORTUNITY AT THIS MOMENT FOR SCIENTIFIC REASONS AND STRUCTURAL REASONS. THE SCIENTIFIC REASONS ARE IN PART SOMETHING YOU JUST HEARD, THROUGH THE REVOLUTIONS IN SEQUENCING AMONG OTHER THINGS, THE MOLECULAR BASIS OF A VERY LARGE NUMBER OF THESE DISEASES IS KNOWN, JOHN GALLIN OR MAYBE STEVE MENTIONED AT THE BEGINNING, THIS IS ABOUT 4,500 RARE DISEASES MOLECULAR BASIS WHICH IS KNOWN AND THERE'S 2 OR 3 NEW ONES THAT ARE DISCOVERED EVERY WEEK IF YOU FOLLOW JOURNALS. SO WHEN YOU ASK WHEN THAT START THAT TREND STARTED IN 1994. SO THIS IS NOT 20 YEARS OLD,S THAT VASTLY DIFFERENT VAIRMT THAN WE WERE IN A FEW YEARSC  AGO. ON THE STRUCTURAL SIDE I THINK WE HAVE WHAT I CAN SEE TWO THINGS GOING ON. ONE IS ORGANIZATIONS WHETHER NIH, FDA, INDIVIDUAL ACADEMIC GROUPS, ET CETERA, THEY ALL AT LEAST IN THIS SPACE SEEM TO HAVE REALIZED OR CRITICAL MASS SEEM THE REALIZE THEY CAN'T DO IT ALONE. HUMAN BEINGS HAVE THIS THING THAT THEY HAVE TO DO IT ALONE UNTIL THEY BEAT LONG ENOUGH THAT THEY BECOME CONVINCED THAT THEY HAVE TO SEEK SOMEBODY HELS'S HELP AND DO IT TOGETHER. WE HAVE ALL BEEN BEATEN ENOUGH THAT REREACH THAT POINT NOW. THAT'S -- WE WOULD BE GREAT TO REACH THIS POINT WITHOUT GETTING THROUGH THAT. BUT HERE WE ARE. AND THAT'S A WONFUL MOMENT. IT ALSO HAPPENS TO COINCIDE WITH WHAT'S GOING ON AT NIH. ON THE 23RD OF DECEMBER LAST YEAR THIS NEW NCATS CENTER WAS FORMED. AND IT FORMALLY BROUGHT TOGETHER THE GROUP THAT I RUN AN JOHN IS INTEGRAL PART OF WITH STEVE GROFIT'S OFFICE, WE WERE COMPLETELY SAID WE DO OUR WORK TOGETHER BUT WE WERE SEPARATE ORGANIZATION. AND WITH THE LARGE CLINICAL TRANSLATIONAL RESEARCH PROGRAM, 60 MEDICAL CENTERS AROUND THE COUNTRY, THOSE ORGANIZES HAVE BEEN BROUGHT TOGETHER UNDER ONE ROOF NOW. SO THAT PRESENTS AN OPPORTUNITY ORGANIZATIONALLY WITHIN NIH TO DO SOMETHING DIFFERENT THAT DIDN'T EXIST FOUR MONTHS AGO OR FIVE MONTHS AGO. THE PRECEDENT PART IS SOMETHING I KNEW A LITTLE BIT ABOUT BUT MORE NOW, THERE'S FANTASTIC EXAMPLES OF THINGS THAT HAVE WORKED AND THINGS THAT HAVE NOT WORKED SO WELL. IN 20 YEARS WE HEARD THE LAST COUPLE OF DAYS. WE NOW HAVE >>MR. JENKINS:IZATION OF THOSE FEATURES IN THE PERSON OF PETRA KAUFMAN SITTING HERE, AND WHO HAS I'LL EMBARRASS BY SAYING THIS, SHE HAS ORCHSTRATE AD CHANGE WITHIN HER OWN INSTITUTE TO FRANKLY FORCE PEOPLE TO WORK TOGETHER. TO DO THIS KIND OF WORK. IN CENTRAL FEDERATED IRB ALL THAT, SO THERE'S A PRECEDENT AT LEAST WITHIN AN INSTITUTE TO DO THIS, AND AS A NEUROLOGIST I CAN SAY THAT EVEN THOUGH YOU MAY THINK THEY WORK ON THE BRAIN, NO, NO, THEY THINK IF YOU WORK OLGD BRAWLG OPPED SPIEWLGT SO SHE SIEWB SEEDED ON THAT ONE. THE OTHER PRECEDENT THAT I WOULD POINT OUT THAT WE HAVE RUN INTO TEN YEARS, DIFFERENCE PART OF THE SPECTRUM, WHICH IS THE GENERAL PROBLEM HOW WE TAKE ADVANTAGE OF THE FACT WE'RE DISCOVERING THE KNEE BONE IS CONNECTED TO THE LEG BONE. WE LEARNED THIS IN KINDERGARTEN BUT ALL OUR TRAINING FORCES US IN THE OPPOSITE DIRECTION. SO I AM A NEUROLOGIST, THAT MEANS I'M NOT A CARDIOLOGIST. SO WE HAVE BRAIN DOCTORS AN HEART DOCTORS AND NOSE DOCTORS AND EYE DOCTORS AN TOENAIL AN BONE DOCTORS, HELLO. IT'S ALL ONE BODY AND ALL USE IT IS SAME PATHWAYS. WE'RE DISCOVERING THAT THOSE PATHWAYS CAUSE MULTI-SYSTEM DISEASE AND MANIFEST IN RARE DISEASE BECAUSE THOSE ARE DESIGNED ON A MULTI-SYSTEM -- BUT PUT'S BEEN HARD WITH NIH TO FIGURE WHERE IS THE LOCUST OF ACTIVITY FOR THAT? IF IT IS A MULTI-SYSTEM. BUT NCATS HAS THAT NOW. SOMETHING WE HAVE RUN INTO IN THE THESE INFORMATICIAN ISSUES ONTOLOGY ISSUES HOW TO BRING PEOPLE IN WITH DIVERSE NEEDS AND GIVE A CENTRAL PHYSICAL AND INTELLECTUAL INFRASTRUCTURE WHICH CATALYZES ALL THE WONFUL EXPERTISE AND KNOWLEDGE AND TOOLS THAT THEY HAVE INTO SOMETHING PRODUCTIVE BY GIVING THEM SOMETHING HERE THAT OFTEN IS A SMALL ELEMENT COMPARED TO WHAT THEY HAVE DONE, WE MANAGE TO DO THAT IN THESE OTHER CIRCUMSTANCES. THERE'S SOME THINGS THAT WE HAVE LEARNED FROM DOING THAT THAT ARE APPLICABLE HERE. AS FAR AS IMPLEMENTATION IS CONCERNED, HAVING BEEN AT NIH NOW SCARES ME TO SAY ALMOST TEN YEARS I HAVE HAD THE PRIVILEGE OF TAKING PART IN A NUMBER OF PROGRAMS THESE LARGE AMBITIOUS TRANSGENOME IF YOU WILL OR TRANSBIOLOGY PROJECTS, AND ALSO ONES THAT INVOLVED THE INTERNATIONAL WORLD, AND NIH IS GETTING GOOD AT DOING THOSE, THE GENOME PROJECT WAS THE FIRST EXAMPLE BUT THERE'S A NUMBER OF OTHERS NOW. AND SO THERE'S -- I WOULD SAY ONE OF THE FIRST THINGS THAT CHARACTERIZED MOST PROSPECTS A PHYSICIAN PAPER. SO HAVING A PUBLICATION, NOT A WHITE PAPER A PUBLISHCATION IN THE LITERATURE THAT TALKS ABOUT SOME OF THE THINGS WE TALKED ABOUT TODAY AND PROPOSING A PLAN A TANGIBLE PLAN FOR HOW TO DO IT IS REALLY IMPORTANT. THAT'S THE COIN OF THE REALM. THAT'S WHERE THE SCIENTIST NEW YORK TIMES, THAT'S WHERE THEY GO ALL THE NEWS THAT FITS THE PRINT IN THE PUBLISHED LITERATURE. WHAT THAT MANAGED TO DO IS IT IS IN MANY CASES SURPRISINGLY ACTED AS A LEGITMIZER. SIMPLY TO HAVE A PAPER THROUGHOUT THAT SAYS WE'RE DO -- WE HAVEN'T DONE ANYTHING YET BUT IT LE LEGITIMIZES THIS PARTICULARLY IF IT HAS AUTHORS ON IT, EVERYBODY WHO ATENNED THE MEETING, PEOPLE WHO'S NAMES PEOPLE RECOGNIZE, THAT MAKE AS BIG DIFFERENCE. THEN IT REQUIRES IMPLEMENTATION GROUP, REALLY DEDICATED PEOPLE, I THINK WE HAVE THAT. BUT THAT CAN'T BE OVERESTIMATED. THE FUNDING ISSUE, JUST SAY SOMETHING ABOUT [CAPTIONING MADE POSSIBLE BY ALABAMA PUBLIC TELEVISION] ING FOR A SECOND. SO I'M A GENETICIST AS WELL AS NEUROLOGIST BY TRAINING AND THIS REMINDS ME OF THE SITUATION ABOUT 15 YEARS AGO, IT WAS EASY TO DO GENETIC LINKAGE STUDIES BUT YOU COULD NEVER GET ANYBODY TO PAY YOU TO COLLECT AN PHENOTYPE THE PATIENTS THAT ARE REQUIRED ON WHICH TO DO LINKAGE STUDIES. IT IS TREMENDOUSLY FRUSTRATING. WE'RE IN THE SAME SITUATION NOW. THE NIH BUDGET IS NOT HAPPY PLACE SO NO WAY N CATS PAYS FOR THIS, IT'S 2% OF THE NIH BUDGET. SO IT'S -- AND N CATS DOES NOT HAVE DOMAIN EXPERTISE. BUT THE GOOD THING ABOUT NCATS, IT'S SUPPOSED TO BE A COLLABORATIVE INSTRUMENT AND THE FACT THAT PETRA IS SITTING HERE AND WAS ALLOWED TO COME TO A MEETING THAT WAS STARTED BY NCATS, THAT SOUNDS FUNNY BUT NIH IS A VERY TRIBAL PLACE. AND SO THERE ARE THINGS CHANGING WITHIN NIH THAT I HAVE SEEN OVER THE LAST TEN YEARS THAT MAKES THIS POSSIBLE. -- THE REASON THAT'S IMPORTANT IS NOT ONLY PRESS DN REASON, WHETHER NEWBORN SCREENING WHICH IS A FANTASTIC IDEA, BUT ALSO IT'S FUNDING BECAUSE 98% COMES FROM OTHER INSTITUTES. THAT SAID, ONE PURPOSE OF THE RTSA PROGRAM IS TO BE A HOME FOR CLINICAL SCIENCE OF THE SORT THAT WE'RE TALKING ABOUT HERE. ONE THING THAT PAIN MESS AS A NEUROLLOLOGIST IS ALL THE WONDERFUL PHENOTYPING, DIAGNOSIS, WHATEVER YOU WANT TO CALL IT, WHICH WAS THE COIN OF THE REALM OF PROUD CLINICIANS, A LOT OF THAT IS GONE BECAUSE OF THE HOGYMYNY OF MOLECULAR GENETICS OVER THE YEARS, THAT HOLDS BECOME OUR ABILITY TO TRANSLATE IN LARGE PART. WE CAN SEQUENCE WITH OUR EYES CLOSED. WE DON'T NEED PEOPLE MANY ANY MORE. SO WHAT WE NEED IS REALLY TOP-NOTCH CLINICIAN WHOSE ARE ABLE TO DO THE OTHER SIDE WHICH IS THE PHENOTYPING. AND THAT'S WHAT THE CTSA SHOULD BE ABLE TO DO. BECAUSE THE CTSA'S ARE WITHIN NCATS WE'LL HAVE SOME ROLE IN THIS. SO I WOULD SAY JUST IN CLOSING, I'M SO DELIGHTED THAT Y'ALL CAME AND ALL THE FOLK WHOSE HAD TO LEAVE BEFORE THE END OF THE SESSION, I WANT TO THANK JOHN FOR A WONDERFUL MAST EARLY SUMMARY OF BOTH SPECIFIC AN GENERAL POINTS AND IF YOU ARE INTERESTED IN SIGNING UP FOR THE MARINES, THE FEW, THE PROUD THE IMPLEMENTATION GROUP, PLEASE TALK TO US, REALIZE THAT WE'RE SERIOUS ABOUT THIS. WE'LL TRY NOT TO BE TOO DEMANDING BUT WE ARE SERIOUS ABOUT NOT HAVING THIS BE A NICE MEETING WHERE WE GET TOGETHER AND DON'T DRINK COFFEE PAUSE WE CAN PAY FOR IT ANY MORE BUT RATHER BE A START OF SOMETHING GREAT. MAKE SURE YOU TALK TO US OR EMAIL US OR SOMETHING AN GOD SPEED ON YOUR WAYS HOME. JOHN. FINAL THOUGHTS. >> NO WAY TO ADD ON TO THAT. THANK YOU AGAIN FOR COMING AND I APPRECIATE THE COMMENTS AND THOUGHTS YOU PUT INTO THE PRESENTATIONS AS WELL AS TO THE DISCUSSION. THE KEY THING ABOUT THIS MEETING WAS IT WAS SUPPOSED TO BE INTERACTIVE AND YOU LIVED UP TO THAT EXPECTATION. SO THANK YOU. AND AGAIN, SAFE TRAVELS HOME. [APPLAUSE]