WELCOME TO THE 166TH MEETING OF THE NICHD ADVISORY COUNCIL. THE MORNING SESSION OF THIS MEETING IS OPEN TO THE PUBLIC AND BROADCAST ON THE NIH VIDEOCAST NETWORK. WE'RE DELIGHTED TO HAVE OUR COUNCIL MEMBERS WITH US TODAY. WE THANK YOU FOR TRAVELING UNDER THE CHALLENGING CIRCUMSTANCES. DR. KOPF IS JOINING REMOTELY AND UNFORTUNATELY MS. LESLIE ROTENBERG AND DR. ANNE CASE ARE UNABLE TO JOIN US. AS A REMINDER, ALL COUNCIL MEMBERS HAVE THE OPTION OF PARTICIPATING REMOTELY FOR ONE MEETING A YEAR. PLEASE REMEMBER TO SPEAK INTO THE MICROPHONE AND STATE YOUR NAME BEFORE SPEAKING. SO THAT THE TRANSCRIBER AND VIDEOCAST KNOW WHO'S SPEAKING WE'RE HAPPY TO HAVE SEVERAL GUESTS TODAY FROM PROFESSIONAL SOCIETIES AND ADVOCACY ORGANIZATIONS. THANK YOU FOR BEING HERE. I ALSO LIKE TO ESPECIALLY MENTION THE GREAT WORK DONE BY THE FRIENDS OF THE NICHD TO PROMOTE AWARENESS OF THE INSTITUTES RESEARCH EFFORTS. THE NEW CHAIR OF THE FRIENDS IS MARRY JOE HUXIMA FROM THE POPULATION ASSOCIATION OF AMERICA AND I BELIEVE SHE IS LISTENING IN THIS MORNING. THE NEW CO-CHAIR WHO I CAME UP IN THE ELEVATOR WITH IS JOE LACCO FROM THE ENDOCRINE SOCIETY WHO IS OBVIOUSLY HERE TODAY. NOW I WOULD LIKE TO TAKE A MOMENT FOR EACH GUEST TO STAND AND INTRODUCE YOURSELF TO WELCOME YOU. >> THANK YOU. WELCOME. THANK YOU FOR ALL THAT YOUR -- YOU AND YOUR ORGANIZATIONS DO TO SUPPORT THE NICHD AND ITS ANYTHING. OMISSION. NOW I'LL TURN THE MEETING OVER TO DR. DE DELLA HANN. >> THIS IS YOUR REMINDER OF CONFLICT OF INTEREST AND CONFIDENTIALITY. ON THE WEBSITE YOU SHOULD HAVE READ AGREED TO AND SIGN THE CONFIDENTIALITY AND NON-DISCLOSE SHOWER RULES FOR SPECIAL GOVERNMENT EMPLOYEES BEFORE YOU EVALUATED THE NIH GRANT APPLICATIONS. ALSO AT YOUR SEATS YOU WILL FIND YOUR RED FOLDER AND INSIDE THAT FOLDER IS A CONFLICT OF INTEREST CERTIFICATION FORM. AS YOU KNOW THE INFORMATION REGARDING YOUR CONFLICTS OF INTEREST IS WHEN DISCUSSING APPLICATIONS AND ISSUES PERTINENT TO SPECIFIC ORGANIZATIONS. IF THERE IS A SPECIFIC DISCUSSION ON ANY ORGANIZATION OR UNIVERSITY FOR WHICH YOU ARE IN CONFLICT, IN ADDITION TO THOSE LISTED ON COUNCIL ACTIONS DOCUMENT, YOU WILL BE REQUIRED TO RECUSE YOURSELF FROM THE DISCUSSION AND TO LEAVE THE ROOM. PLEASE SIGN THE ENCLOSED CONFLICT OF INTEREST CERTIFICATION FORM PRIOR TO CLOSED SESSION THIS AFTERNOON FOR THE REVIEW OF APPLICATIONS. ALSO REMEMBER, THIS IS YOUR BONUS, THAT YOU CANNOT SERVE ON ANY NIH PEER REVIEW PANEL WHILE YOU ARE SERVING AS COUNCIL MEMBER. IT IS NIH'S POLICY THAT INDIVIDUAL CANNOT SERVE ON BOTH FIRST AND SECOND LEVELS OF PEER REVIEW. SO WITH THAT I WOULD LIKE THE TURN NOW TO COUNCIL MINUTES. THE MINUTES FOR THE SEPTEMBER 14th MEETING WERE POSTED ON THE NICHD INTERNET AND COUNCIL MEMBER WEBSITES. AND IF I COULD PLEASE HAVE A MOTION ON WHAT YOU WOULD LIKE TO TAKE WITH REGARD TO THOSE MINUTES. >> MOVE THEIR APPROVAL. >> SECOND. >> ALL THOSE IN FAVOR. ANY NOT IN FAVOR? OR NON-CONCURRENCE? GREAT. THANK YOU VERY MUCH. DR. BUTTE AND KOPF? THEY'RE OKAY WITH IT? GOOD. TERRIFIC. I ALSO JUST NOW WANT TO REVIEW IN PUBLIC SESSION WITH REGARD TO FUTURE MEETING DATES OUR NEXT MEETING WILL BE ON JUNE 7TH WHICH IS A THURSDAY. FOLLOWING THAT WILL BE SEPTEMBER 13th AND 14th AND WE HAVE DECIDED THAT THAT WILL BE A TWO DAY MEETING. SO HOPEFULLY FOLKS WILL INDICATE THAT IN THEIR CALENDARS. IT'S A THURSDAY AND A FRIDAY. FOLLOWING THAT, NEXT JANUARY WILL BE JANUARY 24th OF 2019, JUNE 11th OF 2019, AND SEPTEMBER 19th OF 2019. HOPEFULLY FOLKS CAN INDICATE THAT ON THEIR CALENDARS AND RESERVE THAT SPOT. I WILL NOW TURN THE MEETING BACK TO DR. BIANCHI WHO WILL PRESENT THE DIRECTOR'S REPORT. >> THANK THANK YOU, DELLA. WHAT A DIFFERENCE A YEAR MAKES. A YEAR AGO I WAS GIVING MY FIRST REPORT. SO WE'LL GIVE YOU AN UPDATE ON SOME OF THE THINGS THAT HAPPENED IN THE PAST YEAR. BUT FIRST THE THEME FOR TODAY'S MEETING IS INCLUSION. I KNOW THE COUNCIL MEMBERS HAVE GOTTEN THIS INFORMATIONNARY PACKET BUT FOR THE OTHER ATTENDEES, THERE ARE SOME EXTRA COPIES OF REPRINTS OF OUR JAMA COMMENTARY, WHICH I WILL GO TO IN A MOMENT. ALSO TALK ABOUT NIH POLICY CHANGE THAT OCCURRED THE PAST YEAR AND A PLEA TO INCLUDE POPULATIONS OF INTEREST TO NICHD IN THE ALL OF US PROGRAM. ALSO GOING TO BRIEFLY SAY SOMETHING ABOUT CONGRESS BUT SINCE YOU MAYBE ON YOUR PHONES YOU MAY KNOW MORE THAN I DO AS I STAND UP HERE. BUT WE'LL ALSO GIVE AN UPDATE ON THE 21st CENTURY CURES ACT ACTIVITIES THAT HAVE BEEN UNDER THE PURVIEW OF NICHD DURING THE PAST YEAR. THEN I'LL GIVE UPDATES ON THE VISION FOR NICHD GOING FORWARD. SPECIFICALLY ENHANCING PARTNERSHIPS WHICH WE PREVIOUSLY CALLED BUILDING BRIDGES BUT SINCE SOME OF THOSE EXISTED IT WAS A SOMEWHAT OF A MISNOMER. COMMUNICATING THE MESSAGE. SOME OF THE UPDATES IN COMMUNICATIONS SHARED RESOURCES AND DATA UPDATES AND THEN OUR STRATEGIC PLANNING PROCESS GOING FORWARD. OVER THE PAST MONTHS A LOT OF THINGS HAPPENED THAT REALLY MADE IT APPARENT THAT INCLUSION IS CRUCIAL. THIS WAS CRYSTALIZED IN A VIEWPOINT THAT CATHY AND I WROTE BUT CONTRIBUTED TO BY NUMBER OF OTHER STAFF MEMBERS OF THE NICHD. IT REALLY PERCOLATED FROM A NUMBER OF THE THINGS THAT HAVE BEEN HAPPENING THE LAST FEW MONTHS INCLUDING THE WORK THAT WE'RE DOING WITH THE PREGNANCY AND LACTATION TASK FORCE STUDY MEDICATIONS TAKEN BY PREGNANT AND LACTATING WOMEN. THE INCLUSION WORKSHOP WHICH I'LL TALK ABOUT IN A MOMENT, THEN SOME OF THE THINGS THAT HAVE COME UP IN OUR ADVISORY COUNCIL. BECAUSE OF THAT, WE FELT IT WAS IMPORTANT TO COME RIGHT OUT AND SAY WHAT TRADITIONAL STUDIES OF TRADITIONAL POPULATIONS ARE MISSING. THIS WAS PUBLISHED ONLINE IN JAMA, THE MAIN JAMA, IN VERY QUIET WEEK BETWEEN CHRISTMAS AND NEW YEARS'S BUT DESPITE THE FACT IT'S ONLY BEEN PUBLISHED A FEW WEEKS, IT'S BEEN VIEW VIEWED OVER 12,000 TIMES AND DOWNLOADED I THINK ALMOST 700 TIMES ALREADY. THE POINT OF THE STUDY IS THAT THIS PHILOSOPHY OF EXCLUDING PREGNANT LACTATING WOMEN CHILDREN UNDER AGE 18 ALSO OLDER POPULATIONS OF OVER 65 PEOPLE WITH INTELLECTUAL PHYSICAL DISABILITIES IS MISSING 58% OF THE UNITED STATES POPULATION. WHAT CATHY DID IS ANALYZED PHASE 3 AND PHASE 4 CLINICAL TRIAL DATA THAT WAS AVAILABLE IN CLINICAL CLINICALTRIALS.GOV AND SHOWED THAT APPROXIMATELY 68% OF THE TIME THERE WERE SPECIFIC EXCLUSIONS OF PREGNANT WOMEN IN THESE STUDIES, 47% OF THE TIME THERE WAS INFORMATION ABOUT EXCLUDING LACTATING WOMEN. 75% OF THE TIME EXCLUSION OF CHILDREN AND SMALLER SPECIFIC EXCLUSIONS OF INTELLECTUAL AND PHYSICAL DISABILITIES BUT A LOT OF IT WAS NOT STATED. I'M NOT GOING TO GO INTO THIS HERE NOW BECAUSE MELISSA PARISI, CHIEF OF DEVELOPMENTAL DISABILITIES BRANCH WILL FOCUS ON THAT MORE IN HER POPULATION BUT FROM THESE DATA WE WERE ABLE TO DOCUMENT BY EXCLUDING THESE POPULATIONS THAT WOULDN'T BE REPRESENTATIVE OF THE THE UNITED STATES. IN A PARALLEL ACTIVITY AS MENTIONED BEFORE AT COUNCIL ONE OF CURES ACT RESPONSIBILITIES IN WHICH WE PARTICIPATED WAS THE WORKSHOP SUMMARY OF LIFE SPAN. SO THIS WAS FOCUSED ON AGE, CHILDREN AND OLDER PEOPLE DIDN'T DEAL WITH SOME OF THE OTHER ISSUES. THE VERY SATISFYING THING ABOUT THE WORKSHOP HELD IN JUNE IS IT RESULTED IN AN OFFICIAL POLICY CHANGE AT NIH. SO AS OF NEXT WEEK JANUARY 25th THERE'S A NEW NIH POLICY IN AFFECT THAT REQUIRES APPLICANTS AND GRANTEES TO INCLUDE INDIVIDUALS OF ALL AGES WHEN CONDUCTING CLINICAL RESEARCH UNLESS THERE'S STRONG JUSTIFICATION FOR THEIR EXCLUSION. SO THIS WILL APPLY TO ALL EXEMPT AND NON-EXEMPT HUMAN SUBJECTS RESEARCH. INCLUSION ACROSS LIFE SPAN MUST BE ADDRESSED IN ALL GRANT APPLICATIONS SUBMITTED AFTER JANUARY 25th. WHAT THIS POLICY CHANGE MEANS, IN PROPOSALS THERE HAS TO BE A PLAN FOR INCLUDING INDIVIDUALS ACROSS THE LIFE SPAN AND IF THEY'RE EXCLUDED BASED ON AGE THERE HAS TO BE A RATIONALE FOR WHY THEY'RE EXCLUDED. THE SAME WILL BE TRUE FOR PROGRESS REPORTS. I THOUGHT THIS WAS INTERESTING, DWAYNE, AGE AT ENROLLMENT HAS TO BE GIVEN IN HOURS TO YEARS. SO IF YOU'RE LESS THAN ONE DAY OLD THAT'S IMPORTANT. SO YOU CAN STILL EXCLUDE POPULATIONS. THEY CAN BE EXCLUDED FOR BIOLOGICAL REASONS SO OBVIOUSLY MEN ARE EXCLUDED FROM PREGNANCY STUDIES THAT INVOLVE ACTUAL PREGNANT BODY. THAT'S EXCEPT FOR ARNOLD SCHWARZENEGGER. DIDN'T HE GET PREGNANT IN ONE OF HIS MOVIES? ANYWAY, ACCEPTABLE JUSTIFICATIONS MAY INCLUDE THE FACT THAT THE DISEASE TO BE STUDIED DOESN 'T OCCUR IN EXCLUDED AGE GROUP. THE RESEARCH TOPIC IS NOT RELEVANT TO EXCLUDED AGE GROUP. THE KNOWLEDGE SOUGHT IS AVAILABLE TOKER THE EXCLUDED GROUP. A SEPARATE STUDY FOR THE EXCLUDED GROUP IS WARRANTED OR PREFERABLE. RESEARCH INVOLVES DATA FOR PRE-ENROLLED PARTICIPANTS LAWS OR REGULATIONS BARS INDIVIDUALS SPECIFIC AGE GROUP OR RESEARCH OR STUDY POSES UNACCEPTABLE RISK TO EXCLUDED AGE GROUP, TWO WAYS THINK ABOUT THIS, THERE'S A BIOLOGICAL REASON SO EXCLUDE THE AGE GROUP OR THERE'S AN UNACCEPTABLE RISK. WE'RE HOPING TO CHANGE THE CULTURE TO PROTECT THROUGH RESEARCH BY INCLUDING THESE POPULATIONS OF INTEREST IN OUR RESEARCH STUDIES SO THAT WE CAN OPTIMIZE THEIR CARE. SO IT'S A CHANGE IN PHILOSOPHY PROTECTING THROUGH RESEARCH TO PROTECTING THROUGH RESEARCH RATHER THAN FROM RESEARCH. SO ONE WAY THAT ALL OF YOU AND ALL OF YOU LISTENING CAN HELP NCHD IS TO INCLUDE IN USE CASE STUDIES IN THE ALL OF US RESEARCH PROGRAM CASE STUDIES THAT WOULD INCLUDE POPULATIONS OF INTEREST TO US. FOR EXAMPLE, SPECIFIC STUDIES THAT WOULD INVOLVE USING DATA FROM PREGNANT WOMEN. FROM CHILDREN. FROM PEOPLE WITH PHYSICAL OR INTELLECTUAL DISABILITIES. THE WAY OUR COMMUNITY CAN DO THIS IS TO GO TO THIS WEBSITE, THE ALL OF US COMMUNITY FORUM WEBSITE, YOU CAN SEE THE WEB ADDRESS HERE AND THERE'S A LISTING OF CURRENTLY PROPOSED IDEAS. WHAT THESE ARE IDEAS ON HOW TO USE THE DATA ON MANY PARTICIPANTS ENROLLING INTO ALL OF US. AS YOU MIGHT RECALL INITIALLY THERE WASN'T A MENTION OF CHILDREN IN THE ALL OF US RESEARCH PROGRAM. WE HAVE COME A LONG WAY LAST YEAR IN TERMS OF INCLUDING OUR POPULATIONS IN THE DISCUSSIONS OF ALL OF US. I WANT TO THANK THE MANY NICHD STAFF WHO SPENT A LOT OF TIME BEING INVOLVED IN ALL OF US AND THE MANY MEETINGS TO REMIND THEM THAT CHILDREN, PREGNANT WOMEN, PEOPLE WITH DISABILITIESES ARE VERY IMPORTANT TO STUDY. THE DEADLINE TO COMMENT AND COME UP WITH IDEAS FOR USE OF THESE DATA IS FEBRUARY 9TH AND THEN THE IDEAS CAPTURED BY THE WEBSITE WILL BE CONSIDERED AT A RESEARCH PRIORITIES WORKSHOP COMING UP IN MARCH. THE STUDIES WILL LAUNCH NATIONWIDE, IN BETA TESTING MODE NOW BUT IN THE SPRING. SO PLEASE HELP US TO INCLUDE OUR POPULATIONS. WHAT CAN I SAY ABOUT CONGRESS? WE'RE STILL OPERATING ON A CONTINUING RESOLUTION. INFORMATION WILL BE FORTHCOMING THE NEXT FEW HOURS WHETHER THE GOVERNMENT WILL SHUT DOWN TOMORROW NIGHT AT MIDNIGHT. I DON'T THINK I CAN SAY MORE THAN THAT BECAUSE WE DON'T KNOW MORE THAN THAT. WE HAVE AS I HAVE MENTIONED BEEN INVOLVED IN IMPLEMENTING SEVERAL PARTS OF THE 21st SENT RECURES ACT. I JUST -- CENTURY CURES ACT. I MENTIONED ACROSS THE LIFE SPAN, THE PREGNANCY AND LACTATION TASK FORCE IS ONGOING. THERE IS PROVISION IN THE CURES ABOUT ABOUT MEDICAL REHABILITATION RESEARCH AND ALISON WILL GIVE US A OVERVIEW LATER THIS MORNING. ALISON KERNICH. SO WE TALK ABOUT THIS BEFORE. I DID WANT TO GIVE YOU ABOUT UPDATE THAT THE TRAINING DATA THAT WERE ANALYZED BY NICHD TO CORRELATE FUTURE SUCCESS WITH INDIVIDUAL K AWARDS IS PUBLISHED THIS WEEK ONLINE. WE DON'T HAVE THAT AVAILABLE FOR YOU HERE YET. BUT MAKE IT AVAILABLE FOR YOU ALONG WITH ACCOMPANYING TUTORIAL. EVERYBODY KNOWS WHAT EARLY STAGE INVESTIGATOR IS BUT HAPPENTY SAY IN FISCAL YEAR 2017 WE WERE ABLE TO FUND 20 EARLY STAGE INVESTIGATORS AND COMMITTED SHOULD WE HAVE A BUDGET TO FUND MANY MORE. WE HAVE A VERY HIGH PRIORITY IN OUR YOUNG INVESTIGATORS AND REALLY GIVING THEM THE SKILLS THEY NEED TO BE SUCCESSFUL. SO AS PART OF THAT FOR THE LAST 30 YEARS WE HAVE OFFERED AN ANNUAL YOUNG INVESTIGATORS CONFERENCE, A NUMBER OF US IN THE ROOM ATTENDED, SPOKEN, IT WAS ORIGINALLY HELD IN ASPEN, COLORADO. THEN MOVEDDED TO THE LOVELY SUE BUSHES OF CHICAGO. -- SUBURBS OF CHICAGO. 'S ANNUAL MEETING TO FACILITATE TRAINING OF INVESTIGATORS AND TRADITIONALLY THE PROGRAM WAS OPEN TO FOLLOW AND JUNIOR FACULTY IN NEONATOLOGY, REPRODUCTIVE MEDICINE AND ENDOCRINOLOGY WITH FOCUS ON THOSE THAT PLAN TO BECOME INVESTIGATORS ATTENDEES WERE NOMINATED BY PROGRAM DIRECTORS BUT IN SPECIFICALLY LOOKING AT THIS PAST YEAR'S PROGRAM, THE PROGRAM IS GRAY, IT GETS GREAT REVIEWS. MY CONCERN WAS THAT IT WAS NARROWLY FOCUSED AND REALLY IF WE'RE GOING TO INVEST EFFORTS TO TRAINING THAT GROUP WE SHOULD INVEST EFFORTS IN TRAINING EVEN. SO NEW CONFERENCE WILL FOCUS ON SKILLS BY ANY AND ALL YOUNG CLINICIAN INVESTIGATORS WHOSE ARE WORKING IN AREAS WE FUND SO THIS INCLUDES REHABILITATION MEDICINE. DR. ROSE MARY HIGGINS WILL LEAD THE EFFORT. WE HAVE ALSO DECIDED TO MOVE THE CONFERENCE LOCALLY AT THE BOWLIER CENTER SO FACULTY WHO WILL BE NICHD STAFF CAN PARTICIPATE. WE THINK THIS IS IMPORTANT BECAUSE IT WILL OFFER A GREAT NETWORKING OPPORTUNITY FOR THE YOUNG INVESTIGATORS TO MEET THEIR POTENTIAL PROGRAM OFFICERS. THE ACTIVITY IS SIMILAR TO PREVIOUS COURSE, STUDY DESIGN, MOCK STUDY SECTIONS HOW TO SET UP A WET LAB, WORK LIFE BALANCE AN NETWORKING BUT WE WILL BE ELIMINATING SOME OF THE SCIENCE TALKS AND FOCUS THE CONFERENCE EXCLUSIVELY ON SKILLS NEEDED FOR THE NEXT PHASE OF THEIR LIVES. ALSO IMPORTANTLY WE'RE GOING TO BE INTRODUCING LESSER KNOWN GRANT OPPORTUNITIES, GRANTS THAT ARE UNDERUTILIZED THAT REPRESENT SIGNIFICANT CHANCES TO GET STARTED AS WELL AS CAREER OPPORTUNITIES INCLUDING CAREER OPPORTUNITIES AT NICHD, WHY NOT RAISE THE FARM TEAM FROM THE ATTENDEES OF THIS CONFERENCE SO BEFORE IT WAS FELLOWSHIP DIRECTORS WHO LARGELY HEARD ABOUT THE CONFERENCE, WE WILL BE SENDING INFORMATION TO CHAIRS,PEDIA EXTRA, OBGYN AND REHABILITATION DEPARTMENTS ASKED TO NOMINATE TWO ATTENDEES PER DEPARTMENT SO WE LOOK FORWARD TO YOUR FEEDBACK ON THAT. SO QUICKLY SINCE THE TIME FLIES. ENHANCING PARTNERSHIPS, GOING TO GIVE AN UPDATE ON THAT, COMMUNICATING THE MESSAGE, SHARE DATA AND RESOURCES. SO YOU HAVE HEARD ABOUT NEONATAL OPIOID EXPOSURE, IT'S A BIG HE CAN ISSUE FOR BABIES. DIFFERENT THAN ADULTS. THEY DON'T DIE. IT'S A SIGNIFICANT ISSUE. CLINICALLY, ECONOMICALLY, SOCIALLY, NEONATES IN VARIOUS STATEMENTS OF WITHDRAWAL, OCCUPY SIGNIFICANT NUMBER OF NICU BEDS, SOCIAL SERVICE RESOURCES. AND LOCAL GOVERNMENT EXPENSES FOR FOSTER FAMILY PLACEMENT AND THE PROBLEM THERE'S NO CONSISTENT APPROACH TO CARE FOR MOTHERS AND BABIES. SO WE HAVE DEVELOPED IN PARTNERSHIP WITH ECHO AND NIDA AND TODAY YOU WILL HEAR FROM THE DIRECTOR OF NIDA ABOUT THE ACT NOW PARTNESHIP WHICH COMBINES NEONATAL RESEARCH CENTERS WITH IDEA STATES PEDIATRIC CLINICAL TRIALS NETWORKS IN RURAL AREAS SPECIFICALLY IN AREAS WHERE THERE'S A HIGH PREVALENCE OF OPIOID MISUSE. WE ARE HALFWAY THROUGH THE ONE YEAR PROJECT. GOAL TO INFORM DESIGN OF SUBSEQUENT CLINICAL TRIAL TO TEST THE VARIOUS OPPORTUNITIES FOR CARE AN OUTCOMES FOR INFANTS WITH NEONATAL OPIOID WITHDRAWAL. SYNDROME. WE ARE ALSO BUILDING A BRIDGE ENHANCING A PARTER ENTREPRENEURSHIP WITH THE NATIONAL INSTITUTE ON AGING, YOU WILL HEAR LATER TODAY FROM MR. DAVID EGAN WHO IS A PATIENT ADVOCATE WITH SELF-ADVOCATE WITH DOWN SYNDROME AND DOWN SYNDROME RESEARCH HAS BEEN IN THE NEWS, IT WAS THE SUBJECT OF CONGRESSIONAL TESTIMONY. LOT OF ATTENTION ON FUNDING FOR DOWN CEASE SYNDROME, NIH FUNDS $27 MILLION OF RESEARCH ON DOWN'S SYNDROME. YES PARTNERING WITH NATIONAL INSTITUTE ON AGING TO IDENTIFY ADDITIONAL RESOURCES. SO YOU SEE HERE REPRESENTATIVES FROM SOME OF THE MAJOR PRIVATE FOUNDATIONS THAT FUND DOWN'S SYNDROME RESEARCH. I MET DAVID OUTSIDE IN THE ELEVATOR. AND DAVID AND HIS MOTHER SUGGESTED WE CHANGE THE VOICE OF THE PATIENT SECTION OF OUR COUNCIL TO THE VOICE OF THE PARTICIPANTS SECTION OF COUNCIL. WE REALLY LIKE THAT IDEA BECAUSE DAVID DOESN'T SEE HIMSELF AS A PATIENT. IN FACT WHAT WE'RE TRYING TO EMPHASIZE IS THE BENEFITS OF PARTICIPATING IN NICHD FUNDED RESEARCH WHICH HE HAS. SO WE THINK THIS IS A MUCH BETTER REPRESENTATION OF WHAT WE ARE TRYING TO COMMUNICATE BY INCLUDING A PERSON OR A FAMILY WHO ARE AFFECTED BY PARTICULAR CONDITION. THEY WILL SPEAK LATER THIS MORNING. THE OTHER THING YOU REMEMBER A YEAR AGO I SAID ONE OUR HIGHEST PRIORITIES WAS TO REFRESH THE WEBSITE SO THAT'S GONE LIVE THANKS TO COMMUNICATIONS TEAM AND THE CONTRACTORS. IT WENT LIFE AHEAD OF SCHEDULE. I ENCOURAGE THE COUNCIL TO LOOK AT NEW WEBSITE, SEE IF IT'S EASIER THE FIND INFORMATION IT'S A WORK IN PROGRESS, THERE ARE ERRORSES IN IT. IF YOU FIND ERRORS PLEASE CORRECT THEM. BUT WE'RE VERY PLEASED BOTH WITH ITS PHYSICAL APPEARANCE, BUT MOST IMPORTANTLY IT'S EASE OF USE. COUPLE OF LAST THINGS, SHARED DATA AND RESOURCES, THERE HAS BEEN A TEAM EVALUATING OUR BIOSAMPLES. WHY ARE WE DOING THIS? WE WANT THE MAKE AS IN MANY SAMPLES AS POSSIBLE AVAILABLE FOR PUBLIC USE, MEANING USE FOR APPROPRIATE RESEARCHERS. THIS CAME UP BECAUSE AS WE WERE GOING THROUGH A NUMBER OF CONTRACTS WE FUND WE REALIZE THERE ARE MILLIONS OF DOLLARS BEING SPENT TO STORE SAMPLES THAT MAY OR MAY NOT HAVE MEANINGFUL USE IN THE FUTURE. TWO PARTS TO THIS EFFORT. THERE IS A TEAM OF PEOPLE LOOKING A T THE BIOSAMPLES. THEY'RE ASSESSING HISTORICAL SAMPLES DATING BACK 5, 60 YEARS AND IDENTIFYING THE STRENGTHS, NEEDS AND POTENTIAL DIFFICULTIES IN CREATING POLICIES TO FACILITATE FEATURE SHARING. WHAT THEY HAVE DONE IS CREATE CATEGORIES TO EVALUATE THE HISTORICAL SAMPLES. SO USING THE TRAFFIC LIGHT APPROACH THERE ARE SOME SPECIMENS THERE'S NOTHING SAID ABOUT BEING ABLE TO USE THEM. SO THEY ARE CALLED RED AND WE WILL PROBABLY BE ELIMINATING THEM FROM OUR STORAGE. THE GREENS HAVE CONSENT THAT HAVE UNRESTRICTED FUTURE USE. THE GOOD NEWS IS THERE'S ABOUT 831,000 SAMPLES THAT CAN BE RELABELED AND UP LOADED TO DASH ALONG WITH THE LINK DATA. AND THERE'S ANOTHER GROUP WHICH IT'S UNCLEAR. SO WE WILL BE WORKING WITH THE NEW DIRECTOR OF THE NICHD IRB TO GET SOME CLARITY AND DETERMINE HOW CAN WE GET APPROPRIATE PERMISSION TO USE THOSE SAMPLES. SO I'LL SKIP THIS ONE AND JUST END ON THE STRATEGIC PLANNING PROCESS WHICH IS ONGOING. THEND GOAL FOR THAT IS DETERMINING SCIENTIFIC PRIORITIES FOR NICHD MOVING FORWARD THEN ALIGN RESOURCES WITH THOSE PRIORITIES. WE ARE PROCEEDING AHEAD WITH DETAILS OF THE STRATEGIC PLANNING PROCESS. WE HAVE DEVELOPED A SET OF FOCUS QUESTIONS, AND MEETING P TO POTENTIAL FACILITATOR AT END OF THIS MONTH. WE'LL DEVELOP A PROPOSED WORK PLAN. THE FIRST STEP WILL BE TO HAVE A SMALL NICHD PLANNING SUB-COMMITTEE AND WE WILL INVITE SOME OF THE MEMBERS OF COUNCIL TO PARTICIPATE IN A STRATEGIC PLAN WORK GROUP THAT WILL INCLUDE A ROUND A TOTAL OF 50 PEOPLE INCLUDING COUNCIL MEMBERS INCLUDING NICHD STAFF AND OTHER PEOPLE WHO WORK IN THE EXTRAMURAL WORLD, MEANING OUTSIDE OF NIH. OUR GOAL IS TO ACCOMPLISH THIS LARGELY OVER THIS COMING YEAR. I'M RUNNING OVER SO HAPPY TO TAKE ONE OR TWO QUESTIONS. OKAY. GOOD MORNING, MELISSA, COME ON IN. DR. HANN WILL BE NEXTMENT YOUR SLIDES. >> GOOD MORNING, AGAIN. SO I WANTED TO AS I USUALLY DO GIVE YOU UPDATES ABOUT SOME THINGS GOING ON IN THE EXTRAMURAL WORLD. THAT IS, AGAIN, THE GRANTING WORLD. FOR US ALL HERE. WRONG BUTTON. SO VERY QUICKLY, I'LL BE HITTING ON A COUPLE OF ISSUES. THE FIRST IS A STAFF UPDATE WHICH I NORMALLY DO. AND THEN I WILL BE TALKING IMPACT OF FLEXIBLE FUNDING MODEL. THIS IS CARRY FORWARD OF A NUMBER OF DISCUSSIONS WE HAVE BEEN HAVING HERE AT COUNCIL HOW DO WE GO ABOUT FUNDING THE BEST RESEARCH. SO THAT'S -- I WANT TO SHOW YOU THE REAPING OF OUR REWARD ESSENTIALLY WITH REGARD TO THAT. NEXT IS A QUICK OVERVIEW OF A NEWER PROJECT THAT WE HAVE GONE INTO ON IMPACT ANALYSIS OF LARGE PROGRAMS. I WILL TALK MORE ABOUT THAT WHEN WE GET TO IT FINALLY AN UPDATE OF WHERE WE ARE WITH REFORMS WITH REGARDS TO CLINICAL TRIALS HERE AT NIH AND HOW NICHD IS PLAYING A PART IN THAT. SO THIS LAST FALL I THINK WOULD A HALLMARK WITH REGARD TO NICHD IN THAT WE SAID FAIR WELL TO A NUMBER OF OUR OWN PERSONAL LEADERS HERE AT NICHD. FIRST AND FOREMOST IS DR. (INDISCERNIBLE) AS I ANNOUNCED THE PREVIOUS COUNCIL MEETING TEAL RETIRED. AFTER 31 YEARS OF GOVERNENT SERVICE, 26 WHICH WERE HERE AT NICHD. TEAL WAS A TRUE LEADER WITH REGARD TO DEVELOPMENTAL BIOLOGY AND HE LED THAT BRANCH OF DEVELOPMENTAL BIOLOGY AND STRUCTURAL BIRTH DEFECTS FOR A NUMBER OF YEARS. AND WE GREATLY MISS HIM BUT WE ALSO WISH HIM ALL THE VERY BEST, IN CASE YOU'RE WATCHING US WE HOPE EVERYTHING IS GOING WELL. ANOTHER INDIVIDUAL ALSO WITHIN THAT SAME BRANCH WAS DR. LORETTE JAVO, SHE ALSO RETIRED AFTER ABOUT 17 YEARS OF SERVICE HERE AT NICHD RECALL SHE SPOKE AT THE GABRIELLE LA MILLER KIDS FIRST ACT. HER LEADERSHIP WITH REGARD TO THAT WAS A POWERFUL FORCE NOT ONLY HERE AT NICHD BUT ALSO NIH IN GENERAL. WE ARE STILL TRYING TO FIGURE OUT BASICALLY HOW TO BEST MANAGE AND WORK TO ACCOMPLISH EVEN PARTS OF WHAT LORETTE WAS ABLE TO ACCOMPLISH WHILE HERE. SHE ALSO LED THE STRUCTURAL BIRTH DEFECTS AREA WITHIN THAT BRANCH. SO THAT TOO OF COURSE SHE WAS A POWER HOUSE FOR THAT. WE ALSO SAID GOODBYE WITH REGARD TO RETIREMENT WITH DR. DAVID SEGAL. DAVID TOO HAD BEEN HERE AT NICHD FOR TEN YEARS AND WAS A TRUE LEADER IN WITH REGARD TO HELPING US WITH THE BEST PHARMACEUTICALS CHILDREN'S ACT. DAVID OVERSAW THE PEDIATRIC CLINICAL TRIALS NETWORK, A HUGE NETWORK WE OPERATE IN ORDER TO FULFILL OUR PARTS ESSENTIALLY OF THE BBCA, THE BEST PHARMACEUTICAL CHILDREN'S ACT. THE OTHER PART WHICH MANY FOLKS DIDN'T REALIZE IS THE DAVID WAS INCREDIBLY IMPORTANT IN THE BIODEFENSE AREA. SO SEVERAL YEARS AGO THE UNITED STATES BECAME MUCH MORE INTERESTED IN BIODEFENSE. AND THE HEALTH OF ALL OF US. ESSENTIALLY SHOULD SOME UNTOWARD ACT ACTUALLY OCCUR. AND DAVID IMMEDIATELY BECAME PART OF THAT GROUP EFFORT HERE AT NIH BECAUSE HE WANTED TO MAKE SURE OUR POPULATIONS PARTICULARLY PREGNANT WOMEN AND CHILDREN WERE INCLUDED AND THOUGHT ABOUT WITH REGARD TO DEVELOPING DEFENSE ESSENTIALLY FOR THE UNITED STATES. HE TOO WAS A POWERFUL LEADER WITH REGARD TO OUR PROGRAMS. LAST BUT CERTAINLY NOT LEAST, ALL OF YOU HERE AT COUNCIL WILL REMEMBER KIM WITHERSPOON, KIM HAD BEEN DIRECTOR OF OFFICE OF COMMITTEE MANAGEMENT AND WAS YOUR DIRECT INTERFACE IN MANY REGARDS OVER THE LAST TWO YEARS. SHE WAS DYNAMIC IN TERMS OF REBUILDING IN OFFICE OF COMMITTEE MANAGEMENT AND WE WILL MISS HERMENT SHE DID NOT RETIRE. SHE DID MOVE ON TO FDA TO MOVE INTO A ROLE SHE HAD BEEN LOOKING FOR WITH REGARD TO HUMAN RESOURCE MANAGEMENT SO WE WISH HER THE BEST. SHE TOLD ME THAT SHE WAS GOING TO WATCH US THIS MORNING SO GOOD MORNING, KIM. NOW I'LL MOVE INTO IMPACT OF FLEXIBLE FUNDING MODEL, AS INDICATEDDED TO YOU THIS IS BASICALLY THE OUTGROWTH OF WHAT WE HAVE BEEN WORKING ON HERE AT THE INSTITUTE BASICALLY SINCE I ARRIVED IN 2015. AND LIKELY BEFOREHAND. MANY TIMES OVER TWO YEARS WE HAVE SPOKEN TO YOU ABOUT HOW DO WE GO ABOUT GIVEN OUR BUDGET CONDITIONS AND CHANGES HERE AT NIH HOW DO WE GO ABOUT THINKING HOW FUND THE VERY BEST OF SCIENCE. A NUMBER OF INITIATIVES WERE STARTED AND ACTUAL WILL COMPLETED. ONE VERY IMPORTANTLY THIS LISTED HERE IS THAT WE EACH OF THE BRANCHES IDENTIFY PRIORITY AREAS FOR PREVIOUS RESEARCH. WE WANTED TO USE THESE PRIORITIES ESSENTIALLY TO HELP IN TERMS OF MAKING FUNDING DECISIONS. BUT TO DO THAT, WE ALSO NEEDED TO INCLUDE A LITTLE MORE FLEXIBILITY ESSENTIALLY HOW WE GO ABOUT PAYING AND IDENTIFYING RESEARCH GRANTS TO SUPPORT. SO THIS LAST YEAR IN FY 17, FISCAL YEAR 17 WE DID IMPLEMENT A MORE FLEXIBLE PAY LINE FOR THE RO1s, RO 3s AND R21 GRANTS. WHAT I WOULD LIKE TO DO NOW IS SHOW YOU THE BENEFITS ESSENTIALLY OF DOING THAT. AND I WANT TO GIVE A SHOUT OUT TO OUR DEPUTY DIRECTOR CATHY SPONG THROUGH HER INITIATIVE AND LEADERSHIP THAT WE PURSUED THAT'S EFFORTS AND SHE'S ALSO THE ONE RESPONSIBLE FOR DOING THE DATA ANALYSIS. FOR THIS. THE DATA I'M PRESENTING IS CURRENTLY AVAILABLE ON OUR WEBSITE. DR. BIANCHI BLOGGED ABOUT THIS ACTIVITY. BACK IN NOVEMBER. SO THIS IS AVAILABLE TO THE PUBLIC ADS WELL. THIS IS A GRAPH THAT'S SHOWING YOU THE DIFFERENCES WITH REGARD TO WHAT WE CALL REACHES. BEING ABLE TO SKIP AND REACH FOR PARTICULAR GRANT TO PAY QUOTE OUT OF ORDER. IT'S IMPORTANT TO REMEMBER WE'RE TALKING HIGH QUALITY GRANTS. WE'RE NOT TALKING ABOUT REACHING TO GRANTS NOT VERY HIGH QUALITY. THAT WAS PART OF THE REASON FOR THE FLEXIBLE FUNDING IS WE HAVE A GREAT DEAL OF GRANTS IN IN VIABLE HIGHLY CONSIDERED POOL OF TALENT AND WHAT WE WANTED TO DO IS TRY TO FIGURE OUT A LITTLE MORE STRATEGICALLY HOW TO PURSUE THOSE THAT MAY NOT HAVE JUST FALLEN IN LOCK STEP ORDER. SO YOU WILL SEE FOR THE RO1 POOL, WE DID HAVE AN INCREASE IN THE NUMBER OF REACHES ESSENTIALLY THAT STAFF WERE -- THAT WERE APPROVED. BASICALLY IT STILL -- THIS IS NOT A HUGE NUMBER BUT AROUND NINE, NINE 1/2% AND IT'S SIMILAR FOR THE, AREO 3 AND R21 POOL. COMPARED TO PREVIOUS YEAR FY 16 HOVERING AROUND BETWEEN 5 AND 4%. THERE ARE MANY REASONS FOR DOING THESE REACHES. THE RATIONALE FOR THE REASONS HAS CHANGED. SO FY 16, PRIMARILY THE REACHES WAS GOING ON NATIONAL SENT FOR MEDICAL REHABILITATION RESEARCH AND OUR AIDS PORTFOLIO. AGAIN BECAUSE THERE IS MORE FLEXIBILITY BUILT INTO THOSE LINES OF FUNDING. IN 16 ESSENTIALLY THOSE WERE THE TWO PLACES WE RECEIVED SOME OF ALL THIS GOING ON. HOWEVER IN 17 WHICH IS I WANT TO DRAW YOUR ATTENTION THE BLUE BAARS, THE BLUE BAARS ARE HIGH PROGRAM PRIORITY AREAS. YOU CAN SO THAT THESE WERE USED ADS RATIONALE NOR THOSE REACHES MORE FREAKILY THAN IN THE PAST. -- FREQUENTLY THAN IN THE PAST. IT IS CLEAR WE ARE INDEED USING THIS TOOL, IT'S ALSO CLEAR FROM THE PREVIOUS SLIDE WE HAVEN'T GONE CRAZY, THERE'S NOT A TREMENDOUS AMOUNT OF THIS GOING ON BUT THERE IS A BREADTH OF MORE FLEXIBILITY INTRODUCED INTO ALL OF THIS. SO WE CONSIDER THAT TO BE HIGHLY SUCCESSFUL. THE IMPACT ANALYSIS OF LARGE PROGRAMS. THIS IS A TOPIC THAT HAS BEEN OF INTEREST TO ME AT NIH FOR I DON'T KNOW, 20, 20 SOME ODD YEARS, TO TRY TO FIGURE OUT HOW IT IS WE CAN DEVELOP SOME METRICS TO UNDERSTAND THE IMPACT OF OUR SCIENCE. THIS IS VERY DIFFICULT. AND I THINK IF WE SAT HERE RIGHT NOW AND HAD A DISCUSSION. EACH OF YOU WOULD COME UP WITH DIFFERENT IDEAS WHAT DOES IT MEAN TO HAVE TO SHOW RESEARCH WE'RE SUPPORTING ACTUALLY IS HAVING AN EFFECT. WHAT WE HAVE DONE IS TAKE THIS ON -- TAKE THIS ON BECAUSE PRIMARILY BECAUSE THERE HAVE BEEN CHANGES THAT OCCURRED THE LAST 10, 15 YEARS IN OUR ANALYTIC ABILITIES. THERE'S ALSO CHANGES ESSENTIALLY WITH THE WAY WE STORE DATA. THAT MAKES IT MORE FEASIBLE NOW TO TRY TO UNDERSTAND HOW RESEARCH WE SUPPORTED HAD AN IMPACT IN GIVEN AREAS. SO WHAT WE WERE CHARGED TO DO ESSENTIALLY FROM DR. BIANCHI WAS TO DEVELOP SET OF STANDARD METRICS AND A METHODOLOGY THAT WE CAN USE ON ANY PROGRAM HERE AT NICHD T. WE STARTED WITH LARGE PROGRAMS BECAUSE OF COURSE THOSE REPRESENT MAJOR INVESTMENTS. WHAT IS IMPACT ESSENTIALLY OF LARGER PROGRAMS? AND WE'RE USING THIS TO CHARACTERIZE AND ANALYZE THE PRODUCTS IF YOU WILL OF A LARGE PROGRAM AND MAP THAT PRODUCTIVITY IN TERMS OF NUMBER OF DIFFERENT AREAS. I WILL GO INTO THAT RIGHT NOW. THIS IS A SCHEMA DEVELOPED. I WANT TO GIVE A SHOUT OUT TO DR. BILL DUBLE HERE LEADING THIS EFFORT FOR THE INSTITUTE. FROM BASICALLY WHAT IT REALLY BOILS DOWN TO IS THE PRIMARY PRODUCT, THERE ARE SOME PRIMARY PRODUCTS THAT COME OUT OF RESEARCH, YOU'RE ALL FAMILIAR WITH THOSE. FIRST AND FOREMOST IS PUBLICATION. WITHIN CAN USE THAT PUBLICATION AND FOLLOW ESSENTIALLY NOW ITS FOOTPRINT IN A VARIETY OFFER AREAS. -- OF AREAS. INFORMATION IS PRODUCED. WE AUTOMATICALLY WITH TOOLS WHICH I'LL GET INTO A LITTLE BIT TALK ABOUT IMPACT ON THE FIELD. IN TERMS OF IMPACT FACTOR ET CETERA AND OTHER KIND OF THINGS. WE CAN ALSO DO MORE. WE CAN ALSO TRACK TO SEE IF THAT PARTICULAR PRODUCT MADE ITS WAY IN SOME CASES TO MEDICAL GUIDELINES. GUIDELINES ARE PUBLISHED. PUBLISHED PHENOMENA. THEY SITE REFERENCES. ARE THEY SITED IN THAT. THEY'RE NOW TOOLS ESSENTIALLY THAT POSITIONS AS MANY OF YOU KNOW PHYSICIANS USE ON A RAPID BASIS TO TRY TO UNDERSTAND WHAT TO DO IN A GIVEN SITUATION. THOSE TWO HAVE REFERENCES T. THAT COIN OF THE REALM IF YOU WILL WHICH IS OUR PUBLICATIONS HAS BECOME EVEN MORE ROBUST IN TERMS OF TRYING TO UNDERSTAND AND SEE WHERE WE HAVE HAD PARTICULAR KINDS OF IMPACT. OF COURSE THERE'S THE NEWS OUTLETS AS WELL. EVEN SOME INSURANCE GUIDELINES HAVE REFERENCES. SITING RESEARCH BECAUSE THE OVERWHELMING CONSENSUS THAT WE NEED EVIDENCE BASE ESSENTIALLY TO WHAT WE'RE DOING. BUT THAT'S NOT THE ONLY PRODUCT. THERE ARE A NUMBER OF OTHER PRODUCTS THAT CAN EMERGE, ONE OF COURSE IS PATENTS. AND ONE CAN FOLLOW THAT TO SEE WHAT IMPACT HAS BEEN IN TERMS OF DEVELOPING A GIVEN TECHNOLOGY TOOL BIOLOGIC, ITS. I THINK THE OTHER AREA THAT WE'RE ABLE TO ALSO LOOK AT PRETTY ROBUSTLY HAS TO DO WITH TRAINING IN TERMS OF WE CAN FOLLOW PEOPLE BETTER THAN WE WERE ABLE TO 10, 15 YEARS AGO IN TERMS OF WHAT IS THE IMPACT OF THAT EXPERIENCE WITH ALL THOSE INDIVIDUALS WHO ARE PART OF THAT NETWORK, WHAT HAS BEEN THE IMPACT IN TERMS OF THEIR ABILITY TO CONTINUE ON INTO RESEARCH. SO THE METRICS WE HAVE DEVELOPED, THERE'S A TOOL THAT WAS DEVELOPED BY COLLEAGUES OF OURS HERE AT NIH, CALLED THE RELATIVE CITATION RATIO. TO UNDERSTAND FOR A GIVEN AREA OF SCIENCE, WHAT IS ITS RELATIVE CITATION RATIO COMPARED TO OTHERS IN THAT FIELD? SO IT'S BEEN MODIFIED IN ORDER TO TAKE INTO ACCOUNT NOT ALL FIELDS ESSENTIALLY HAVE A SAME LEVEL OF PRODUCTION AND NOT ALL FIELDS DO THE SAME KINDS OF CITATIONS EITHER. SO IF YOU ARE LOOKING AT A GIVEN PAPER RELATIVE TO FIELD, WHAT IS ITS CITATION RATIO. AS INDICATED WE'RE AGE LOOK AT PATENTS, GUIDELINES, CLINICAL SUPPORT TOOLS, PUBLIC ARENA IS THE NEWS ARENA. WE'RE ALSO TRYING ESSENTIALLY TO LOOK AT IMPACT IN TERMS OF POLICIES AND LEGISLATIONS. THAT MAYBE A LITTLE BIT MORE A TIME SERIES ANALYSIS AS OPPOSED TO FOLLOWING A SPECIFIC REFERENCE BECAUSE SOMETIMES OUR LEGAL DOCUMENTS DON'T PROVIDE REFERENCES. BUT WE CAN DO TIME SERIES ANALYSIS ON THAT. MANY OF THIS IS ALSO DEPENDENT ON DEVELOPING A COMPARISON GROUP FOR THAT PROGRAM. THAT TOO IS FACILITATED BYE-BYEBLY OWE METRIC DATA HOE BIBLE METRIC DATABASES. IT'S POSSIBLE TO IDENTIFY POCKETS OF RESEARCH AND FIND OTHER POCKETS OF SIMILAR RESEARCH THROUGH TOOLS THAT EXIST HERE AT NIH. INTERWOVEN IN THIS TOO IS THEMATIC CONTENT. WE HAVE TOOLS AVAILABLE AGAIN U DEVELOPED HERE AT NIH, TO LOOK AT THEMES OF RESEARCH AND PLOT ESSENTIALLY THE AMOUNT OF ACTIVITY GOING ON IN A GIVEN THEME. AND THEN LOOKING AT THAT OVER TIME. IT'S ALMOST LIKE A TIME SERIES ANALYSIS TO SAY WELL, 25 YEARS AGO THERE WERE PAPERS ON ON PREGNANCY, NEONATOLOGY, RESUSCITATION, DA DA DA DA. AND YOU CAN LOOK AT THE GROWTH IN THAT FIELD OVER TIME AND PARTICULARLY TAG THAT LARGE PROGRAM TO SEE HOW IT INFILTRATED OTHER AREAS OF SCIENCE. THAT'S WHAT I REFER TO IN TERMS OF SCIENTIFIC LEADERSHIP BECAUSE FOR LARGER PROGRAMS THOSE ARE VERY MUCH WHAT WE ARE LOOKING FOR IS THEIR FLAG SHIFT ACTIVITIES WHICH MEANS THEY SHOULD BE TREND SETTERS FOR THE FIELDS. YOU'RE SAYING WHAT WERE THE PROGRAMS WE STARTED WITH. SO WE STARTED WITH FIVE PROGRAMS AND STARTED WITH FIVE VERY DIFFERENT PROGRAMS. THE FIRST IS MATERNAL FETAL MEDICINE NETWORK. FROM NEXT IS LEARNING DISABILITY AND RESEARCH CENTERS. WE HAVE THE PEDIATRIC HIV AIDS COHORT STUDY. THE NATIONAL CENTERS FOR TRANSLATIONAL RESEARCH AND REPRODUCTION AND INFERTILITY. AND POPULATION DYNAMICS CENTERS P THESE ARE VERY DIFFERENT. THEY HAVE VERY DIFFERENT OUTCOMES. AND WE CHOSE THEM VERY SPECIFICALLY FOR THIS THAT BECAUSE AGAIN WHAT WE ARE TRYING TO DO IS DEVELOP A BATTERY, IF YOU WILL, OF ANALYTIC TOOLS THAT WE CAN LOOK ACROSS ANY LARGE PROGRAM NOT EXPECTING THE PROGRAM ESSENTIALLY TO BE HIGH FLYING IN ALL THOSE AREAS. WE EXPECT THERE TO BE DIFFERENCES BUT THE BEAUTY WILL BE IT WILL BE THE SAME SETS OF MEASURES. SO THAT ONE CAN ACTUALLY TRY TO FOCUS -- TO CONSOLIDATE AND INTERPRET THIS INFORMATION IN A WAY WE HAVE NEVER BEEN ABLE TO DO BEFORE. SO THESE PROGRAMS WERE CHOSEN, WE ARE ON A FAST TIME TRACK IN THAT WE WANT TO HAVE ANALYSIS COMPLETED ESSENTIALLY WITHIN THE NEXT MONTH AND A HALF SO IT'S AVAILABLE FOR OUR STRATEGIC PLANNING PROCESSES. MY UNDERSTANDING IS WE WILL PROBABLY CHOOSE DEPENDING ON SUCCESS OF THIS, TO CHOOSE ADDITIONAL PROGRAMS GOING FORWARD. SO THE NEXT ACTIVITY I WANT TO DATE YOU ON -- UPDATE YOU ON IS CLINICAL TRIAL REFORMS. EVERY TIME I HAVE BEEN HERE I HAVE TALKED ABOUT CLINICAL TRIALS. SO THIS IS STILL YET ANOTHER CHAPTER IN THAT BOOK WITH REGARD TO ALL REFORMS GOING THROUGH. THIS TIME THOUGH INSTEAD OF SAYING IT'S COMING, IT'S COMING, IT'S COMING, IT'S HERE. IF YOUD ON YOUR COLLEAGUES ESSENTIALLY RIGHT NOW ARE PREPARING GRANT APPLICATIONS FOR NIH, YOU ARE IN THE THICK OF THIS MORE THAN LIKELY. BECAUSE IT HAS IT HAPPENED. THE FOA SUBMISSION POLICY IS NOW. SO RECEIPT DATE THAT IS COMING UP NEXT WEEK, END OF NEXT WEEK, THE NEW POLICY HAS GONE INTO AFFECT. MEANING IF YOU ARE DOING A CLINICAL TRIAL DEFINED BY NIH AS CLINICAL TRIAL, THEN YOU NEED TO COME IN ON A FUNDING OPPORTUNITY ANNOUNCEMENT THAT IS SPECIFICALLY ALLOWING FOR CLINICAL TRIALS. THIS HAS BEEN I CAN TELL YOU THERE ARE MANY AREA OF OUR PORTFOLIO THAT FOLKS HAVE BEEN ASKING LOTS OF QUESTIONS. DO I, DO I NOT HAVE A CLINICAL TRIAL. THE WAY AS I TALKED TO YOU BEFORE, THE WAY NIH HAS DEFINED THIS IS RATHER BROAD. IT DOESN'T MATCH WHAT FOLKS TYPICALLY CONSIDER CLINICAL TRIAL. IT IS IMPORTANT FOR THE INVESTIGATOR TO MAKE UP THEIR MINDS ESSENTIALLY WHAT THEY HAVE AND CHOOSE THE BEST FOA THAT MATCHES THEIR PURSUIT F. ALONG WITH THAT, IT HAD BEEN DEVELOPMENT OF NEW APPLICATION FORMS THAT WILL I ALLOW FOR DIFFERENT KIND OF INFORMATION TO BE ADDED IF ONE IS HAVING PROPOSING A CLINICAL TRIAL. THAT IS WHERE THE NEXT BULLET, THE NEW HUMAN SUBJECTS AND CLINICAL TRIAL FORMS ARE INCLUDED IN THERE. ADS Y'ALL KNOW TOO ANY TIME WE PUT OUT NEW FORMS THAT LEADS TO LOTS OF QUESTIONS. WE HAVE GOT QUESTIONS UPON QUESTIONS UPON QUESTIONS, WE'RE GRATEFUL PEOPLE ASK US F. WE DO OUR BEST IN TERMS OF POINTING OUT RESOURCES, PROVIDING PIECES OF INFORMATION. I WILL SAY THIS WILL BE AN INTERESTING CHALLENGE ESSENTIALLY FOR ALL OF US. IN TERMS OF ADOPTING THIS. THEY HAVE ALSO -- WE HAVE ALSO INCLUDED IN THIS ROLL OUT THE CHANGES IN THE APPENDIX POLICY. PRIOR TIMES WHEN ONE WAS PROPOSING A CLINICAL TRIAL THEY MAY HAVE INCLUDED AS APPENDIX THE PROTOCOL OR THE DRAFT OF THE PROTOCOL THAT WILL NO LONGER BE ACCEPTED. UNLESS IT'S SPECIFICALLY REQUIRED IN FUNDING OPPORTUNITY ANNOUNCEMENT. THE RATIONALE FOR THAT IS THAT WITH THE CHANGES IN THE FORM, THE PRIOR BULLET,, YOU'RE ACTUALLY INCLUDING SOME OF THOSE ELEMENTS ALREADY IN YOUR APPLICATION. IT'S GOING TO BE THERE. THE OTHER THING COMING INTO PLAY OF COURSE IS THE USE OF THE SINGLE IRB. ANY HUMAN SUBJECTS RESEARCH, IT DOESN'T HAVE TO BE A TRIAL, ANY HUMAN SUBJECTS RESEARCH THAT IS MULTIPLE SITES IN THE UNITED STATES VERSUS DOMESTIC NEEDS TO COME IN WITH A SINGLE IRB. YOU MAY REQUEST A WAIVER BUT THE BAR IS RELATIVELY HIGH. THERE ARE SOME KNOWN REASONS ESSENTIALLY WHEN THAT WILL NOT WORK. FOR EXAMPLE WORKING WITH TRIBAL NATIONS THAT WILL NOT WORK. HOWEVER IN MOST OTHER CASES THERE'S THE EXPECTATION IS THAT IT WILL WORK. FINALLY THERE IS THE BIG PRIZE, IF YOU WILL, THAT KIND OF STARTED THIS WHOLE EFFORT IN TERMS OF CLINICAL TRIAL REFORMS WHICH IS THE REGISTRATION RECORDING AND CLINICALTRIALS.GOV. IF YOU ARE CONDUCTING WHAT NIH CONSIDERS TO BE A CLINICAL TRIAL YOU WILL BE REQUIRED TO ENTER INFORMATION INTO CT.GOV AT THE TIME YOU'RE ABOUT TO LAUNCH THE STUDY AND REPORTING THE RESULTS IS ALSO REQUIRED WHEN STUDY IS COMPLETED. IN RESPONSE TO THESE CHANGES WE HERE AT THE INSTITUTE THROUGH LEADERSHIP OF MEREDITH TEMPLE O'CONNER AND GENE HYUNGA HAVE WRITTEN AND PUT ON THE STREET FOUR NEW FOAs FOR INVESTIGATOR INITIATED CLINICAL TRIALS. WE ELECTED TO USE THE RO1, THE R21, THE RO 3 AND THE R 15 FOR THIS FIRST WAVE. IF YOU ARE AROUND THE TABLE THOSE IN THE ETHER WHO ARE LISTENING IF YOU'RE DOING A CLINICAL TRIAL, PLEASE, PLEASE LOOK AT OUR FOAs IN TERMS OF WHICH ONE BEST MEETS YOUR NEEDS. WE ARE PLANNING TO JOIN SOME ADDITIONAL FOAs THAT ARE BEING PRODUCED BY NIH FOR THE SBIR STTR COMMUNITIES. AND I THINK A FEW OTHERS ARE CONSIDERING AS WELL, DEPENDS ESSENTIALLY ON HOW WELL WE'RE PLAYING WITH OUR NEIGHBORS. AND WHETHER WE CAN GET SOME OF THE PIECES IN THAT WE WANT ESSENTIALLY INTO THOSE ANNOUNCEMENTS OTHERWISE WE WILL DO IT OURSELVES. OF COURSE WE'RE CONTINUING TOPIC SPECIFIC FOAs. SO TO MEET OUR SPECIFIC PORTFOLIO NEEDS. SO SOME OF THE CONCEPTS ESSENTIALLY WE'RE GOING TO BE TALKING ABOUT TODAY ARE EXAMPLES OF THAT. THOSE WILL BE SPECIFIC, THEY WON'T RELY ON INVESTIGATOR INITIATED KINDS OF FOAs. SO WITH THAT, THOSE ARE MAJOR POINTS I WANTED TO BRING OUT AND I'M STILL ON TIME. SO THANK YOU. IF ANYONE HAS ANY QUESTIONS I'M HAPPY THE ADDRESS THEM. YES, GEORGE. >> THANK YOU, DELLA. GREAT PRESENTATION. I I'M GOING TO COMMENT A LITTLE BIT ON THE IMPACT ANALYSIS. THAT'S AMAZING REALLY. THANK YOU. THAT'S TREMENDOUS EFFORT. BY TIME YOU'RE DONE I'M SURE IT WILL BE A MODEL FOR A LOT OF OTHER EFFORTS IN OTHER INSTITUTES. I KNOW YOU THOUGHT ABOUT IT AND YOUR GROUP HAS THOUGHT ABOUT THIS FOR A LONG TIME BUT I JUST HAVE THREE SUGGESTIONS. FIRST IS MAYBE YOU CAN INCLUDEN IMPACT ON OUTCOMES OF THESE DISEASES. FOR EXAMPLE, WE KNOW THAT THE 076 TRIAL FOR AZT WHEN HAPPENED WHEN IT WAS PUBLISHED AND YOU CAN TRACK MATERNAL TO CHILD TRANSMISSION OF HIV AND WE CAN SEE TREMENDOUS DROP, THAT'S AN IMPACT. MAGNESIUM FOR NEUROPROTECTION FOR EXAMPLE YOU CAN TRACK CEREBRAL PALSY RATES AFTER IT WAS PUBLISHED. SO THAT COULD LEND SOME MORE WEIGHT TO THE IMPACT. >> TOTALLY AGREE WITH YOU. WE ARE LOOKING AT SOME OF THESE PUBLISH HEALTH INDICATORS AS WELL. THAT PIECE OF IT IS STILL A LITTLE BIT UNDER DEVELOPMENT BUT WE ARE INCLUDING THAT FOR THAT LEVEL OF WHERE I HAD MORE POLICY POPULATION LEVEL. >> SECOND SUGGESTION IS TO TAKE THE FIELDS RELATIVE TO THEIR FIELD. I KNOW YOU MENTIONED SOMETHING RELATIVE BUT SOME ARE SLOWER THAN OTHERS. OR TO COMPLETE TRIALS. IF YOU'RE DOING A TRIAL IN OBSTETRICS IN PREGNANT WOMAN AND YOU HAVE FIVE YEAR FOLLOW-UP OF THE CHILDREN, THAT WILL TAKE TEN YEARS EASILY. FOR IT TO COME OUT AND THE GUIDELINES AND THEN EVEN TO HAVE SOME IMPACT. WHILE HORSE IF YOU'RE DOING SOMETHING THAT'S SAY COOLING IT COULD TAKE A FEW YEARS TO COME OUT IN THE GUIDELINE. SO WINDOWS OF THESE ARE DIFFERENT FOR DIFFERENT FIELDS. THE THIRD FINAL COMMENT, DON'T FORGET ABOUT NEGATIVE TRIALS. MOST OF THE FOCUS IS ON POSITIVE TRIALS AND WHAT THEIR IMPACT IS, BUT NEGATIVE TRIALS DON'T MAKE IT TO GUIDELINES. AND DON'T -- WE THINK THEY DON'T HAVE IMPACT BUT THEIR IMPACT IS THAT THEY PREVENTED A HARMFUL INTERVENTION OR COSTLY INTERVENTION FROM BEING DEPLOYED IN CLINICAL CARE. SO FOR EXAMPLE FETAL HEART RATE MONITORING THERE WERE A LOT OF COMPANIES AND A LOT OF TECHNOLOGIES BEING PUSHED ON THE PROVIDERS TO BE IMPLEMENTED AND NEGATIVE TRIALS STOP THAT. AND THIS WILL NOT SHOW UP IN ANY GUIDELINES OR ANY -- THANK YOU. >> ALL VERY GOOD. I THINK ONE OF THE THINGS I HAVE TRIED TO EMPHASIZE, I DIDN'T HERE AND I APOLOGIZE, THESE ARE MEASURES. THE INTERPRETATION HOWEVER OF WHAT THEY MEAN WILL VARY. AND IT WILL REQUIRE ESSENTIALLY PROGRAM OFFICIALS Z WELL AS INDIVIDUALS WHO ARE KNOWLEDGEABLE IN THE FIELD TO HELP US WITH THAT INTERPRETATION. SO I TOTALLY AGREE WITH YOU. AND I THINK THAT HAD BEEN WHAT HAS BEEN ONE OF THE SIGNIFICANT CHALLENGE FOR EVEN PRODUCING ESSENTIALLY A STANDARD SET OF MEASURES. IS THAT THE MEASURE IS A MEASURE. BUT WHAT EIGHT MEANS ESSENTIALLY IS REALLY CONTEXTUAL. THAT PART HAS TO BE ADDED AND IT CAN'T BE PART OF THE MEASURE. >> PLEASE UNDERSTAND, I APPLAUD THE EFFORT AND I'M VERY INTERESTED. THANK YOU. >> SIMILAR TO GEORGE, I LIKE THE FRAMEWORK AS WELL. I HAVE TWO QUESTIONS. ONE IS, IS THAT AVAILABLE FOR PEOPLE TO SEE? SECOND, RESEARCHERS WERE OFTEN TARGETING THE PUBLICATION FEES BUT WHAT YOU ARE LOOKING FOR IS THINGS THAT HAVE TO DO WITH COMMUNICATION IN OTHER AREAS. SO I WONDER HOW INTENTIONAL Y'ALL ARE BEING AROUND SOME OF THESE OTHERS THINGS THAT MATTER AND ARE THERE WAYS WHICH YOU ARE ABLE TO SUPPORT OR ENCOURAGE RESEARCHERS TO THINK ABOUT THESE OTHER DOMAINS, THINKING A LITTLE MORE DYNAMIC. >> >> SURE. U THINK ACTUALLY IN MY MIND YOUR TWO QUESTIONS ARE HIGHLY ENTERRELATE. WITH REGARD TO -- INTERRELATED. WITH REGARD TO MAKING IT KNOWN WHAT THE FRAMEWORK IS AND WHAT WE'RE DOING, I THINK WE DO HAVE EVERY INTENTION OF MAKING THIS AVAILABLE. IT'S STILL A WORK IN ART RIGHT NOW SO I'M GIVING YOU AND IN THE IN THE MIDST OF IT UPDATE BUT WE HAVE INTENTION OF HAVING THIS PUBLIC. WE HAVE HAD GREAT INPUT ESSENTIALLY FROM COLLEAGUES EAR AT -- HERE AT NIH, IN OFFICE OF SCIENCE POLICY, WHO NOT ONLY DEVELOPED SOME OF THESE TOOLS BUT HAVE BEEN THINKING ABOUT THIS A VERY LONG TIME. SO THEY TOO I THINK ARE SEEING THIS AS GEORGE INDICATED A VERY GOOD OPPORTUNITY TO REALLY SHOWCASE ESSENTIALLY SOME OF THE TOOLS THAT WE HAVE AVAILABLE AND THEREFORE EVERY EFFORT WILL BE MADE TO MAKE IT PUBLIC. WE THOUGHT THOUGH CERTAINLY NOT THERE YET IN TERMS OF PUBLICATION BUT ALSO IN TERMS OF WEBSITE MAKING THIS INFORMATION AVAILABLE. I THINK BY SUGGESTING THESE ARE OTHER AVENUES THAT THAT WILL HELP ESSENTIALLY INVESTIGATORS TO THINK ABOUT THAT. SOMETIMES. I THINK MANY OF US WHEN DOING OUR RESEARCH, WE HAVE THAT IN SOME AREAS. THAT IS THE END GAME SO THE EXAMPLE YOU GAVE GEORGE WITH REGARD TO CHANGES IN HIV CLEARLY WE SEE THAT AS IMPORTANT. IN TERMS OF POPULATION STATISTICS AND WHO GUIDELINES. SO WE'RE TRYING TO AMASS THAT SO WE CAN HAVE THAT IN OUR DATABASES SO WE CAN LOOK FOR THAT FOOTPRINT THAT GOES THROUGH. OTHER AREAS OF SCIENCE, THAT'S NOT THE FOCUS, IT'S MORE IMMEDIATE ON THE AREA OF SCIENCE AND LOOKING FOR TRENDS AND CHANGES IN SCIENCE THAT EVENTUALLY MAY HAVE A RIPPLE AFFECT. BY PRODUCING THIS FRAMEWORK MORE PUBLIC SCALE PERHAPS WILL GET THEM THINKING HOW DO I DO THAT, HOW MIGHT BE WAYS IN TO PUSH THIS ENVELOPE FURTHER AND POTENTIALLY FASTER. >> I THINK WE NEED TO MOVE ON BECAUSE WE HAVE A REALLY BUSY MORNING. SO THANK YOU, DR. HANN, THANK YOU MEMBERS OF COUNCIL, WE WILL HAVE THE BREAK TO EXTEND THE DISCUSSION. AS MOST OF YOU KNOW, A SIGNIFICANT PROPORTION OF NICHD FUNDED RESEARCH IS FOCUSED ON IMPROVING THE LIVES OF PEOPLE WITH PHYSICAL AND/OR INTELLECTUAL DISABILITIES. DURING TODAY'S ADVISERY COUNCIL MEETING WE WILL HAVE A NUMBER OF PRESENTATIONS TO GIVE YOU AN OVERVIEW OF OUR RESEARCH PORTFOLIOS IN THIS AREA. SO FIRST WE HAVE DR. ALISON KERNICH NICHD DIRECTOR OF REHABILITATION RESEARCH WHO WILL PRESENT ON REHABILITATION RESEARCH AT THE NIH, TRENDS AND FUTURE DIRECTIONS. >> THANK YOU, DR. BIANCHI. I LOOK FORWARD TO UPDATING Y'ALL. 'S BEEN TWO YEARS SINCE I PRESENTED TO COUNCIL THERE SHALL'S A LOT THAT HAPPENED IN THE REHABILITATION COMMUNITY SINCE WE FIRST PRESENTED. WHEN WE STARTED WE SAID WE WERE MOVING THE FIELD FORWARD AND I NOW FEEL LIKE WE'RE A WHEELCHAIR GOING UPHILL, WE NEED TO MAINTAIN THE MOMENTUM AFTER A DOWNHILL SPRINT. PICTURED HERE COLLEAGUES ACROSS THE NIH WHO WORKED ON REHABILITATION ISSUES IN PHYSICAL DISABILITY COGNITIVE DISABILITY, SENSORY DISABILITY, AND CARDIAC PULMONARY IRISSUES AND REHABILITATION OF THOSE INJURIES. WE COLLABORATED CLOSELY AND SOME OF THE INFORMATION YOU WILL SEE HERE IS REALLY THE RESULT OF THE WORK OF THESE GOOD PEOPLE. JUST TO GIVE YOU A SCOPE OF WHAT'S HAPPENED SINCE 2012, THE REHAB PORTFOLIO ACROSS NIH HAS GROWN ABOUT $100 MILLION. SO THERE'S INCREASED INTEREST IN THIS AREA ACROSS NIH. AND WHAT WE CONTINUE TO DO IS TRY TO LOOK AT WHERE WE INVEST OUR DOLLARS AND WHAT ASPECT OF REHABILITATION WE NEED TO ADDRESS WITH RESPECT TO GAPS. THE OTHER THING WE DEAL WITH IS THAT AS DR. BIANCHI MENTIONED IMPLICATIONS FROM THE CURES ACT FOR US THAT INCLUDED US UPDATING RESEARCH PLAN, COORDINATING COMMITTEE, AT NIH MAKING RECOMMENDATIONS FOR RESEARCH PRIORITIES, AND MAKING SURE ADVISORY BOARD INCLUDED MEMBERS LIKE DR. HANN MENTIONED WHO WERE INVOLVED IN THE ANALYSIS AND PRIORITIZATION OF SCIENTIFIC PROGRAMS IN THE NIH SPECIFICALLY THE DIRECTOR OF DPKPSI. WE HAVE MADE PROGRESS ON EVERY SINGLE ONE OF THESE OTHER THAN THE INCLUSION OF THE DEFINITION OF MEDICAL REHABILITATION RESEACH. WE PUBLISHED OUR RESEARCH PLAN PRIOR TO THE ENACTMENT. SO WE DID NOT HAVE THAT DEFINITION AVAILABLE. TO SPEND A LITTLE TIME ON THE NIH RESEARCH PLAN ON REHABILITATION, THIS WAS A YEAR AND A HALF EFFORT THAT CROSSED NIH. THIS IS NOT DIAGNOSTICALLY FOCUSED. THE RESEARCH PLAN CREATED INVOLVED 17 INSTITUTES AND CENTERS, WE HAD A PERIOD OF PUBLIC COMMENT AND SCIENTIFIC WORKSHOP TO HELP US FOCUS THE PRIORITIES IN THIS PARTICULAR RESEARCH PLAN. WHAT WE DECIDED IS THAT BECAUSE WE DIDN'T HAVE BENEFIT OF TIME TO DO A LOT OF DATA ANALYSIS TO HELP SCOPE THE PORTFOLIO, WE WOULD SCOPE EFFORTS AND THEN TRY TO DO ANALYSIS ON THE BACK END TO TRACK PROGRESS THAT WAS RELATED TO THIS PLAN. JUST TO GIVE ORIENTATION, REHABILITATION ACROSS THE LIFE SPAN DEALS WITH BOTH MATURATION AND DEVELOPMENT ASPECTS DEFERENCES BETWEEN PEDIATRIC VERSUS REHABILITATION AND OLDER ADULTS BUT ALSO DOSING INTENSITY MECHANISMS RELATED TO REHABILITATION. COMMUNITY AND FAMILY IS MORE AROUND THE INTEGRATION OF THE PERSON WITH THE COMMUNITY AND PARTNERING WITH THE PERSON AND CARE PROVIDER AND CARE GIVEN IF NEEDED AND ENHANCE THE SCIENCE IN THAT AREA, TECHNOLOGY USE AND DEVELOPMENT IS SORT OF THE BRED AND BUTTER OF REHABILITATION IN DEVICES. BUT ALSO ALGORITHM DEVELOPMENT AND RESEARCH DESIGN AND METHODOLOGY IS WHERE WHERE ASPECTS OF THE TRIAL LIVE. TRANSLATIONAL SCIENCES IS MORE BASE BASIC TRANSLATIONAL SCIENCES THE CELL ORGANISM TISSUE OREN ANIMAL MODEL AND BUILDING RESEARCH AND INFRASTRUCTURE. WE HAVE BEEN WORKING ON ESTABLISHING A BASELINE. SO PRIOR TO THE PLAN BEING PUBLISHED, WHAT DID THE PORTFOLIO LOOK LIKE IN 2015? SO I HAVE NO WORDS TO SAY HOW MUCH WORK DR. JENNIFER JACKSON IN THE NATIONAL CENTER FOR MEDICAL REHABILITATION RESEARCH HAS DONE WITH ME. WE HAVE SPENT COUNTLESS HOURS TOGETHER GOD LOVE HER. SO WHAT WE HAVE DONE IS WORKED WITH OUR COLLEAGUINGS ACROSS THE NIH TO CREATE A FRAMEWORK AND RULES AND WE HAVE CATEGORIZED REHABILITATION RESEARCH PORTFOLIO AND YOU CAN DO THIS YOURSELF AT HOME IF YOU WOULD LIKE. YOU CAN TAKE THE CATEGORY FROM 2015 PUT IN EXCEL SPREADSHEET AND HAND CATEGORIZE EACH PROJECT. THERE'S 1370. SO I WILL TELL YOU IT DOESN'T TAKE LONG. BUT WHAT WE DID WAS WE SAID OKAY FINE, HOW ARE THE GRANTS FALLING OUT AND DISTRIBUTED AS A WITH OUR PLAN PRIORITIES? THE BULK OF OUR INVESTMENT IS IN RESEARCH DESIGN AND METHODOLOGY. EITHER IN CLINICAL TRIALS OR IN USING EXISTING DATA TO ANSWER QUESTIONS ACROSS ALL VARIOUS ASPECTS. IS AND THE PROPORTIONS STAY THE SAME WHETHER YOU LOOK AT NUMBER OF GRANTS, VERSUS THE MONEY INVESTED. FROM THE OTHER THING WE LOOKED AT WAS THE PHASE OF RESEARCH. SO IS IT MORE BASIC RESEARCH AT TISSUE ORGANISM LEVELER APPLIED CLINICAL TESTING INTERVNTIONS IN HUMANS? THE BULK O OUR WORK IS TESTING INTERVENTIONS IN HUMANS. WE HAVE ALSO USED AS DR. HANN -- THIS IS AN HOUR LONG PRESENTATION, I'M HAPPY TO GIVE IN A PRIVATE SETTING. WE DO HAVE THE I TRANSTOOLS LOOK AT IMPACT ON CLINICAL PRACTICE GUIDELINES AND TRANSLATION TO PATENTS AND BIOLOGICS. AND WE PRESENTED THAT AT OUR BOARD MEETING IN DECEMBER. AGAIN, THIS DOES NOT CHANGE AND IN FACT IT GROWS, IF YOU LOOK AT PROPORTION, THE HUMAN INTERVENTION IS BULK OF SPENDING. WE ALSO WORKED WITH THE NIH LIBRARY VERY SIMILAR TO DR. HA IN,N'S APPROACH TO LOOK AT THEMATIC ANALYSIS IN TERMS OF TYPES OF INVESTMENTS WE'RE MAKING RESEARCH PROJECTS. SBIR, STTR ACROSS THE INSTITUTE WHO ARE LARGER INVESTORS AND THEN USING SPECIFIC TERMS, WHAT ARE WE INVESTING IN. YOU SEE WITH CLINICAL RESEARCH NEUROSCIENCE BEHAVIORAL SOCIAL SCIENCE AND BIOENGINEERING. THESE ARE OVERLAPPING BUT IT DOES GIVE A THEMATIC SENSE WHERE REHAB DOLLARING ARE GOING ACROSS NIH. IN TOTAL FUNDING DOESN'T CHANGE, NOR THEMES SO WE'RE CONSISTENT IN THE WAY WE FUND RESEARCH. THE OTHER THING WE'RE DOING GREAT DEAL OF IS WORKSHOPS AND THESE ARE REALLY COLLABORATIVE WORKSHOPS, NOT ONLY ACROSS NIH BUT ACROSS THE FEDERAL GOVERNMENT. WE WORK WITH THE INTERAGENCY COMMITTEE ON DISABILITY RESEARCH TO PLAN AND THEN HOST WITH NINDS SUPPORT OPTIMIZING FOR REHABILITATION AND INCLUDED NOT ONLY FEDERAL PARTNERS FROM VA, DOD, NSF AND NIDALER BUT ALSO ACRONYMS FOR EVERY OTHER FEDERAL AGENCY THAT SPONSORS REHABILITATION RESEARCH, WE ALSO HAVE OUR COLLEAGUES FROM FDA AND CENTER FOR MEDICARE MEDICAID SERVICES THERE TO TALK ABOUT THE IMPLICATIONS OF RESEARCH AS IT RELATES TO POLICY. THE VIDEOCAST IS AVAILABLE, IT WAS A FASCINATING MEETING BECAUSE IT DID TALK ABOUT IMPACT OF RESEARCH AS IT TRANSLATES TO GETTING DEVICES IN HANDS OF CONSUMERS. WE SPOKE ABOUT INTERAGENCY COLLABORATION. THIS HAS BEEN SOMETHING REHABILITATION FIELD HAS DONE VERY WELL FOR A NUMBER OF YEARS. WE WORKED THIS YEAR WITH NCCIH TO PROMOTE DOD NIH PAIN INITIATIVE WHICH IS AN INITIATIVE TO LOOK AT NON-OPIOID APPROACHES TO PAIN MANAGEMENT. AND CMRR IS FUNDING ONE OF THOSE PROPOSALS AND NICHD AND NINDS AND NIGH YAMS ARE PARTNERING. WE ALSO HAVE NUMBER OF INTERAGENCY WORK GROUPS INCLUDING THE COMMITTEE ON DISABILITY AND REHABILITATION, I'M WORKING WITH A COLLEAGUE FROM NINDS AND THE GROUP AT NIDLER TO COME UP WITH GOVERNMENT WIDE INVENTORY THAT LOOKS SIMILAR TO THE NIH PORTFOLIO ANALYSIS WE HAVE NOW. WE PARTICIPATE IN EACH REVIEW AND HAVE ENTERED INTERAGENCY AGREEMENTS AND I WANT TO THANK OUR COLLEAGUE THERESA PRESENTIER WHO IS WORKING WITH DISTRIBUTION AGENCY, IT'S ON THE STREET NOW AND WE HOPE PEOPLE ARE READING IT AND RESPONDING. THE OTHER DIRECTION WE'RE TAKING WHICH IS A DIFFERENT VENUE FOR US IS LOOKING AT INTERNATIONAL WORK. OUR PORTFOLIO HAS NOT BEEN INTERNATIONALLY FOCUSED NOR HAS OVERARCHING REHAB GROUP BEEN INVOLVED AT INTERNATIONAL LEVEL. WE WERE INVITED BY THE WORLD HEALTH ORGANIZATION TO A NUMBER OF STRATEGIC MEETINGS TO PLAN FOR REHABILITATION 2030. THOUGH THIS IS MORE FOCUSED ON INCLUDING REHABILITATION IN HEALTH SERVICES, ACROSS THE GLOBE, AND INCORPORATING IT IN DISASTER PLANNING, SO THERE CAN BE STEP DOWN FROM ACUTE SERVICES TO REHABILITATION AS REQUIRED, THERE NEEDS TO BE RESEARCH ASPECT TO THIS AS WE GET MORE COUNTRIES INVOLVED. SO I HAD THE OPPORTUNITY TO VISIT BRAZIL THIS YEAR TO TALK ABOUT EFFORTS IN LOW AND MIDDLE INCOME COUNTRY AND WE WILL WILL HAVE A VISIT IN TWO WEEKS TO TALK ABOUT CONTINUING RESEARCH AGENDA. OUR FOCUS WILL BE IN THE AREA OF PRIORITY ASSISTIVE PRODUCTS WHO IDENTIFIED 50 AND MANY OF THEM ARE WELL ALIGNED WITH THE RESEARCH THAT IS BEING DONE AT NIH. THE OTHER THING TO MENTION, I MENTION IN ALL TALKS IS RESEARCH INFRASTRUCTURE NETWORK IS A VERY SOLID PIECE OF OUR RESEARCH PORTFOLIO AND IS CO-SPONSORED BY SOME OF THE OTHER INSTITUTES INCLUDING NIBIB AND NINDS. WE ARE WORKING WITH THEM IN A COORDINATED WAY TO PROMOTE REHABILITATION RESEARCH, DR. DR. BONINGER HERE WHO LEADS THE REHAB CENTER AND FABIAN EYEBROW SHAH IS NOW PI OF THAT. THE TREATMENT CENTER IS FOCUSED ON MEDICAL DEVICE TRANSLATION TO COMMERCIAL MARKET. WE HAVE A CENTER ON NEUROMODULATION RESEARCH WHICH NIMH IS NOW MORE INTERESTED IN THE WE HAVE A CLINICAL TRIALS FOCUS CENTER TO DO LARGE DATA RESEARCH FOR REHABILITATION USING PUBLICLY AVAILABLE DATA. AND CENTER ON MOTOR SIMULATION. THESE HAVE BEEN GREAT AVENUES TO ENHANCE REHABILITATION RESEARCH TO TEACH SPECIFIC SKILLS AND GET NEW TRAINEES MORE ENGAGED IN REHABILITATION RESEARCH. SO I THINK THAT I HAVE CAUGHT US UP SLIGHTLY. WITH MY PRESENTATION. AND CAN TAKE PROBABLY ONE QUESTION BEFORE I TRANSITION TO DR. PARISI. >> THANKS FOR THAT. JUST TO CONNECT THE DOTS BETWEEN YOUR PRESENTATION AND DR. BIANCHI'S EARLIER. CAN YOU GIVE A SENSE OF THE FOCUS ON CHILDREN OR CHILDREN WITH DISABILITIES IN THE OVERALL STRATEGY? >> THERE'S A LOT MORE DATA THAT WE HAVE AND WE HAVE AGE CLASSIFIED. THE CHALLENGE THAT WE HAVE WITH AGE CLASSIFICATION AS DR. BIANCHI MENTIONED IS THAT THE CLASSIFICATION IS 21 AND YOUNGER. SO THE STUDIES SORT OF HYPERINFLATE. WE HAVE TO LOOK MORE SPECIFICALLY AT THE INCLUSION CRITERIA FOR EACH OF THE GRANTS TO SEE WHETHER OR NOT THEY HAVE HIGH PEDIATRIC FOCUS BECAUSE NOW IT LOOKS OVERREPRESENTED. I WILL TELL YOU THAT'S ONE OF THE THINGS THAT WE'RE LOOKING AT IN OUR HAYNALSIS AND WE HAVE SEEN I LOOKED AT 1370 GRANTS MYSELF. THE REHABILITATION FOCUS FOR CHILDREN IS LACKING. IT IS SOMETHING WE'RE DISCUSSING IN OUR GROUP BECAUSE MOST STUDIES ARE FOCUSED IN ADULT. SO THESE ARE ALL GENERALLY POPULATIONS WITH EITHER CHRONIC OR TEMPORARY DISABILITY THAT THE PORTFOLIO ANALYSIS IS CONCENTRATED ON. INTELLECTUAL DISABILITY IS INCLUDED. BUT ONLY IF IT INVOLVES AN INTELLECTUAL DISABILITY USUALLY REFERRED TO AS HABILITATION INTERVENTION THAN REHABILITATION INTERVENTION SO WE'RE LOOKING HOW THE CATEGORY BREAKS OUT BECAUSE WE USE ONLY OFFICIAL REHABILITATION CATEGORY AND NOT STUDIES ON DISABILITY GENERALLY. >> WHERE WOULD HABILITATION, I UNDERSTAND THAT DISTINCTION. WHERE WOULD THAT >> SO THERE ARE SOME IN THE PORTFOLIO. BUT IT WOULDN'T REPRESENT THE BULK OF THE INTELLECTUAL DEVELOPMENT -- DEVELOPMENTAL DISABILITIES BRANCHES WORK. ANY OTHER QUESTIONS? WITH THAT I WILL YIELD. >> THANK YOU NOR THAT UPDATE ALISON. IT'S IMPORTANT FOR PEOPLE TO RECOGNIZE THE NATIONAL CENTER FOR MEDICAL REHABILITATION RESEARCH IS TRANS-NIH ACTIVITY HOUSED IN NICHD. AND IN FACT MAJORITY OF FUNDED STUDIES ARE ON ADULTS. SO THAT MAKES IT VERY DIFFICULT WHEN TALKING TO PEOPLE ABOUT WHAT THE INSTITUTE DOES THAT WE ARE FUNDING RESEARCH AN REHABILITATION FROM STROKE IN ADULTS. SO NEXT WE'RE GOING TO WELCOME DR. MELISSA PARISI, NICHD CHIEF OF THE INTELLECTUAL DEVELOPMENTAL DISABILITIES BRANCH. DR. PARISI WILL PROVIDE US AN UPDATE ON INTELLECTUAL AND DEVELOPMENTAL RESEARCH AT NICHD TRENDS AND FUTURE DIRECTIONS, DISABILITIES. I LEFT OUT DISABILITIES. SORRY. >> THANK YOU FOR THE INTRODUCTION. I APOLOGIZE FROM MY THROAT I'M RECOVERING FROM A COLD SO I HAVE HERBAL TEA TO HELP ME GET THROUGH. WHAT I WOULD LIKE TO TALK ABOUT TODAY IS TO GIVE YOU A LITTLE BRIEF OVERVIEW OF THE GENOMICS REVOLUTION AND HOW THIS IS CREATED UNPRECEDENTED OPPORTUNITIES AS WELL AS SOME SIGNIFICANT CHALLENGES FOR THE IDD POPULATION AND IN PARTICULAR MAKING ADVANCES IN THE FIELD. BUT THEN I WOULD ALSO LIKE TO TELL YOU ABOUT SOME OF THE PROGRESS IN IDDRC, DEVELOPMENTAL DISABILITIES RESEARCH CENTERS PROGRAM, THAT IS ADDRESS SOME OF THESE CHALLENGES AND FINALLY CLOSE WITH SOME COMMENTS ON INCLUSION AND INFORMED CONSENT. SO FIRST, GENOMICS REVOLUTION. NOT GOING INTO A LOT OF DETAILS ABOUT GENOMICS AND SEQUENCING BUT I THINK IT'S IMPORTANT TO KNOW THAT THE DIFFERENCE BETWEEN THE OLD WAY WE USED TO SEQUENCE DNA AND THE NEW WAY WE SEQUENCE DNA IS REALLY REVOLUTIONARY. IN THE PAST KNOW BOTH PROCESSES START WITH DNA FRAGMENTS, IN THE PAST YOU WOULD BASICALLY SEQUENCE ONE FRAGMENT AT A TIME. IN A CAPILLARY OR GIVEN REACTION. TODAY WITH THE TECHNOLOGIES AVAILABLE, THERE CAN BE A MILLION READS PER RUN. SO THE VOLUME OF THE DATA GENERATED ARE SIGNIFICANTLY GREATER THAN WHAT THEY WERE IN THE PAST. AND PERHAPS AN EASIER ANALOGY TO APPRECIATE ONE OR TWO LANE ROAD VERSUS A MEGA SUPERHIGHWAY. SO WHAT THIS MEANT IS THAT WE CAN NOW SEQUENCE COMPLETE HUMAN GENOME IN A FRACTION OF THE TIME, FRACTION OF THE COST, IN THE PAST. FIRST COMPLETE HUMAN GENOME SEQUENCED IN EARLY 2000s, COST OF $1 BILLION, TOOK 13 YEARS. TODAY WE CAN DO A COMPARABLE SEQUENCE OF HUMAN GENOME IN A COUPLE OF DAYS AND FOR COST OF COUPLE OF THOUSAND DOLLARS. SOME INDUSTRY EXPERTS PREDICT THAT COST IS GOING TO GO DOWN TO $100 AND TAKE AS LITTLE AS AN HOUR. WE'RE NOT THERE YET BUT ESSENTIALLY THERE'S HOPE AND POTENTIAL FOR US TO BE AT THAT RATE. WHAT THAT RESULTED IN THOUGH IS REAL ISSUES BECOME THOSE OF DATA STORAGE OF ALL THIS INFORMATION AND MORE IMPORTANTLY DATA INTERPRETATION. HOW DO WE MAKE SENSE OF THESE VOLUMES AND VOLUMES OF DATA. FROM A PRACTICAL PERSPECTIVE ONE OF THE BARRIERS TO IMPLEMENTING THE GENOMIC REVOLUTION FOR THOSE WITH INTELLECTUAL DISABILITIES HOW CAN WE APPLY GENOMIC TESTING IN THE CLINIC FOR DIAGNOSIS OF INDIVIDUALS WITH IDD HOW TO INTERPRET VARIANTS THESE APPROACHES. IN PARTICULAR THERE ARE MANY POTENTIALLY CONDITIONED CAUSING VARIANT. HOW DO YOU NARROW DOWN THE LIST TO FIGURE WHAT'S IMPORTANT? AND IF YOU DO IDENTIFY A VARIANT OF INTEREST, HOW DO YOU SHOW THAT IT IS FUNCTIONALLY SIGNIFICANT? SO THIS BECOMES A CHALLENGE IN DETERMINING WHETHER VARIANT IS PATHOGENIC OR BENIGN OR MANY CASES VARIANT FALL INTO THIS CATEGORY OF VARIANT OF UNCERTAIN SIGNIFICANCE WHICH ARE REALLY A CHALLENGE BECAUSE WE COMMENT DON'T KNOW WHAT TO DO WITH THEM. ONCE WE IDENTIFIED VARYING INTERPRETATIONS HOW TO LEVERAGE NEW EFFORT FOR GENE DISCOVERY AND HOW TO TRANSLATE THESE DISCOVERIES TO DEVELOP WHICH IS THE HOLY GRAIL FOR GENE AT THIS COVERRY FOR THE INTELLECTUAL DISABILITY POPULATION. SO HERE IS ONE APPROACH TO MAKING CLINICAL SIGNIFICANCE OF THE VARIETY OF GENETIC VARIATIONS THAT MAYBE IDENTIFIED IN THE SINGLE HUMAN BEING. SOME STRATEGIES ARE SEGREGATION PATTERN OF GENOMIC VARIANT IN FAMILY, YOU CAN ALSO LOOK TO SEE FREQUENCY VARIANT IDENTIFIED IN A POPULATION CONTROLLED DATABASE, TELL YOU WHETHER OR NOT IT'S FUNCTIONALLY SIGNIFICANT. YOU CAN LOOK AT FUNCTIONAL EFFECTS AND PREDICTED IMPACT OWN PROTEIN FUNCTION BY VARIOUS ALGORITHMS AND TRYING TO MODEL WHAT THESE GENOMIC VARIANT MIGHT DO IN A MODEL SYSTEM. FINALLY YOU CAN ROOK AT DISEASE VARIANT DATABASES AND SEE WHETHER OR NOT THESE VARIANT HAVE BEEN PREVIOUSLY IDENTIFY OR IF THEY HAVE BEEN ASSOCIATED WITH GIVEN PHENOTYPES OR SIMILAR CLINICAL PRESENTATIONS. SOME OF THESE DATABASES INCLUDE CROWD SOURCING APPROACHES WHERE PATIENTS OR FAMILIES CAN ENTER THEIR OPEN INFORMATION OWN GENOMIC VARIANT AND SEE WHETHER THERE'S A MATCH IDENTIFIED. SOME OF THESE APPROACHES ARE INCREDIBLY POWERFUL FOR RARE VARIANT PARTICULARLY. WHAT WE WANT TO BE ABLE TO DO IS TWO FROM THE CLINIC TO THE RESEARCH REALM AND REALLY BACK TO THE CLINIC. IT REQUIRES AN INTERDISCIPLINARY COLLABORATIVE APPROACH WHERE YOU ARE ABLE TO LOOK AT FUNCTIONAL ANALYSIS OF CANDIDATE VARIANT, YOU MAYBE EMPLOYING BIOMATERIALS OR BIOSPECIMENS SUCH AS SKIN FIBROBLASTS OR LYMPHOCYTES OR OTHER TISSUES TO TEST HYPOTHESES AND THEN ESSENTIALLY RESULTING IN CLINICAL TRIALS SOME OF WHICH MAYBE BASED PREDOMINANTLY ON THE FINDINGS OF GENETICS RESULTS. SO THIS IS A GOAL. THIS GRAPH SHOWS PROGRESS THAT'S BEEN MADE IN DIAGNOSTIC YIELD FOR INTELLECTUAL DISABILITIES OVER TIME WITH REGARD TO VARIOUS TECHNOLOGIES THAT HAVE BECOME AVAILABLE. IN THE 1970s AND '80s IF A PATIENT CAME TO GENETICS CLINIC OUR YIELD FOR BEING ABLE TO MAKE DIAGNOSIS WAS SOMEWHERE ON THE ORDER OF 5%. ALL WE HAD WAS A CHROMOSOME TEST OR KARYOTYPE. WITH ADVENT OF FLUORESCENCE IN SITU HYBRIDIZATION LARGE SCALE DELETIONS OR DUPLICATIONS OF GENETIC MATERIAL THAT YIELD INCREASED TO AROUND 15, 20%. WITH GENOMIC MICROARRAYS IN EARLY 2000S WE COULD DETECT SMALLER DELETIONS OR DUPLICATIONS OF GENOMIC MATERIAL AND YIELD WENT UP 20, 25%. BUT IT'S REALLY WITH ADVENT OF NEXT GENERATION SEQUENCING TECHNOLOGIES INCLUDING WHOLE EXOME SEQUENCING AND WHOLE GENOME SEQUENCING WHERE YIELDS HAVE BEEN MORE IN THE 60 TO 70% RANGE SO THIS REALLY HAS CREATED INCREDIBLE OPPORTUNITIES FOR US. IN FACT CURRENTLY THE NUMBER OF GENES IDENTIFIED THAT ARE RELATED INTELLECTUAL DISABILITIES IS SOMEWHERE ON THE ORDER OF 600 TO 700. THESE REPRESENT VARIETY OF INHERITANCE PATTERNS. ONCE WE HAVE IDENTIFIED A GENETIC CAUSE, FOR A GIVEN INDIVIDUAL'S INTELLECTUAL DISABILITY THAT'S ONLY THE TIP OF THE ICEBERG BECAUSE THAT LEADS TO OTHER ADDITIONAL QUESTIONS AND CHALLENGES IN TRANSLATING THAT INFORMATION INTO REAL WORLD SCENARIOS THAT IMPROVE THE HEALTH OUTCOMES FOR PEOPLE WITH INTELLECTUAL DISABILITIES. HERE ARE SOME OF THOSE CHALLENGES. WE HAVE LIMITED KNOWLEDGE OF THE BIOMARKERS, THE TARGET MOLECULES AND PATHWAYS INVOLVED IN SUCH COMPLEX HUMAN PROCESSINGS AS COG ANYTHING. -- COGNITION. THOUGH WE HAVE SOME ANIMAL MODELS VERY FEW MODELS REPLICATE THE COMPLEX HUMAN INTELLECTUAL DISABILITY PHENOTYPES THAT WE'RE INTERESTED IN. AND WHEN WE DO HAVE THOSE MEASURES IT MAYBE DIFFICULT TO RELY BLISS REPRODUCE MEASURES AND BE ABLE TO CORRELATE BETWEEN HUMANS AND ANIMALS. THERE IS ALSO THE INCREASING COMPLEXITY OF CO-MORBID CONDITION SUCH AS EPILEPSY SLEEP PROBLEMS AND MENTAL HEALTH PROBLEMS THAT IMPACT NUMBER OF PEOPLE WITH INTELLECTUAL DISABILITIES THAT ARE HARD TO MODEL AND UNDERSTAND. WE HAVE A POOR UNDERSTANDING OF NATURAL HISTORY OF MANY OF THESE RARE IDD CONDITIONS, THE PROBLEM OF SMALL ENDS, AND THERE'S ALSO A BROAD RANGE OF ABILITIES FOR KNOWN CONDITIONS. WE HAVE HAD FAILURES OF UNDERSTANDING THE ROLE OF ENVIRONMENT EPIGENETICS AND COMPLEX IDD PHENOTYPES AND THERE'S OOH A NUMBER OF FAILURES OF HIGH PROFILE DRUGS IN PHASE 2 TO 3 RANDOMIZED CLINICAL TRIALS, PHARMACEUTICAL INDUSTRY REPRESENTATIVES SO COMPANIES ARE HESITANT TO INVEST IN COGNITION ENHANCING TREATMENTS BECAUSE THEY HAVEN'T BEEN VERY SUCCESSFUL. IN PART BECAUSE THERE HAVE BEEN FEW DRUGS FOR COGNITIVE OUTCOMES WE PROBABLY HAVE BEEN HAMPER BY INSENSITIVE OR INAPPROPRIATE END POINTS AND OUTCOME MEASURES. SO IF THERE WAS EFFECT WE WEREN'T USING THE RIGHT TOOL TO MEASURE IT. THERE MAYBE INADEQUATE STRATIFICATION LOOKING AT THE WRONG TIME FRAME FOR DEVELOPMENTAL PROCESS. AND FINALLY ONE OF THE ISSUES SIGNIFICANT IS PLACEBO EFFECTS IN THIS POPULATION. AND THAT'S HAMPERED THE ABILITY TO SHOW A SINGLE BY A GIVEN DRUG. FINALLY IF WE DO HAVE APPROPRIATE INTERVENTIONS, THERE HAVE BEEN CHALLENGE WITH DISSEMINATION AND IMPLEMENTATION OF TREATMENTS INTO PRACTICE. SO THIS IS ONE OF THE PROGRAMS I WOULD LIKE TO HIGHLIGHT THAT TRYING TO ADDRESS SOME OF THESE CHALLENGES AND THIS IS THE EUNICE KENNEDY SHRIVER INTELLECTUAL AND DEVELOPMENTAL DISABILITIES RESEARCH PROGRAM NAMED AFTER EUNICE KENNEDY SHRIVER, NAME SAKE OF OUR INSTITUTE IN 2008. THIS PROGRAM WAS ORIGINALLY CONGRESSIONALLY MANDATED SOON AFTER THE FOUNDING OF NICHD AND THE CONGRESSIONAL LEGISLATION REQUIRED CONSTRUCTION OF 12 BRICK AND MORTAR CENTERS THAT WERE FOCUSED ON RESEARCH WHAT WE KNOW AS INTELLECTUAL DISABILITIES. IN THE 1990s, THIS PROGRAM WAS TRANSITIONED TO A P-30 MECHANISM FOCUSING ON INFRASTRUCTURE COARSE AND ENCOURAGING TRAINING OPPORTUNITIES. IN 2013 WE CONVERTED THIS TO A COOPERATIVE AGREEMENT MECHANISM WHICH A MORE FOCUS RESEARCH PROJECT TRANSLATIONAL EMPHASIS AND CREATION OF A NETWORK OF IDDRCs. CURRENTLY EACH CENTER INCLUDES SHARED RESOURCES AND FACILITIES IN THE FORM OF CORES, SPECIFIC RESEARCH PROJECT FUNDED BY EACH CENTER THAT SERVES AS A SHOWCASE WITH RESEARCH AT THAT CENTER. THERE ARE ADDITION A.M. RESEARCH PROJECTS INDEPENDENTLY FUNDED BY NIH FOUNDATION AND OTHER MECHANISMS. EACH CENTER SUPPORTS ABOUT 30 TO 70 PIs AND BETWEEN 50 AND 100 PROJECTS. IDDRC IS PLAYING AN IMPORTANT TRAINING ROLE TO ATTRACT INVESTIGATORS TO THE FIELD AND LEVERAGE MANY OTHER RESOURCES TYPICALLY AT LEAST $20 MILLION IN INSTITUTIONAL SUPPORT PER ITDRC. RECENTLY THE PROGRAM CELEBRATED 50 YEARS OF IDD RESEARCH. AND THE CURRENT GOAL EVOLUTION FROM FOUNDING 50 YEARS AGO, IS REMOTE COLLABORATIVE MULTI-DISCIPLINARY RESEARCH PROGRAMS TO ADVANCE DEVELOPMENT OF THERAPIES AND INTERVENTIONS FOR IDD CONDITIONS. THERE ARE 14 IDDRCs ACROSS THE NATION WITH FAIRLY GOOD GEOGRAPHICAL DISTRIBUTION. IN THE EARLY YEARS, MANY OF THE IDDRC RESEARCH FOCUSED ON EARLY INCLUSION PROJECTS AND EDUCATIONAL INTERVENTIONS. AND I WANTED TO HIGHLIGHT THE UNIVERSITY OF WISCONSIN, WASTEMAN SENTENCER IN MADISON WHICH YOU WILL HEAR ABOUT WITH DAVID EGAN'S PRESENTATION WHERE HE GOT SOME OF HIS EARLY EDUCATIONAL START AT THIS IDDRC. AS I MENTIONED THIS PROGRAM HAS BEEN VERY IMPORTANT IN PROMOTING TRAINING OF THE NEXT GENERATION OF IDD RESEARCHERS AND IN FACT OVER THE PAST FIVE YEARS ABOUT 300 PRE-DOCTORAL OR GRADUATE STUDENTS HAVE BEEN TRAINED THROUGH DIFFERENT IDDRCs AND OVER 600 POST-DOCTORAL TRAINEES. TODAY'S TRAINEES ARE VERY FOCUSED ON SOME OF THESE MULTI-DISCIPLINARY COLLABORATIVE RESEARCH EFFORTS WHICH IS INCREDIBLY IMPORTANT TO SEE ADVANCES IN THE FIELD. A NUMBER OF COLLABORATIVE WORK GROUPS ARE FORMED THROUGH IDDRCs ADDRESSING THE TRANSLATIONAL CHALLENGES I DESCRIBED TO YOU. THERE'S A PROJECT INVENTORY WORK GROUP DEVELOPED INVENTORY OF OVER 150 PROJECTS AND RESOURCES ACROSS ALL CENTER INCLUDING RARE DISEASES TO INCREASE END FOR COLLABORATIVE PROJECTS THAT ARE NOW OVER 60 PROJECTS THAT INCLUDETOR TWO OR MORE IDDRCs TAKING ADVANTAGE OF THIS RESOURCE AND ADDITIONAL COLLABORATIONS. THERE'S A GENOMICS VARIANCE WORK GROUP DEVELOPING SHARED PROJECTS TO IDENTIFY FUNCTIONALLY VALIDATE AND CURE RATE RARE OR PREVIOUSLY UNKNOWN VARIANT OF IDDRC MUCH AS I DESCRIBED PREVIOUSLY. THIS IS IMPORTANT FOR INCREASING THE DATA THAT POPULATE MUTATION DATABASES THAT ARE AVAILABLE. THE ANIMAL CORES WORK GROUP IS DEVELOPING PROTOCOLS TO LOOK FOR COMMON RODENT BEHAVIORAL ASSAYS. FOCUSED ORNERY GOSH AND REPRODUCIBILITY IN RODENT BEHAVIORAL RESEARCH CRITICAL TO ENSURE THE TESTS WE'RE DOING ON ANIMAL MODELS ACTUALLY ARE MEANINGFUL AND REPRODUCIBLE AND RELEVANT FOR HUMAN BEHAVIORAL PHENOTYPES. AND THIS PAPER WAS JUST PUBLISHED ONLINE ABOUT A WEEK AGO. THE FIRST OF MANY PAPERS. THE CLINICAL TRANSLATIONAL CORES WORK GROUP IS DEVELOPING SHARED PHENOTYPING EFFORTS AND TOOLS EXPLORING WAYS TO LEVERAGE INFORMATICS AND REGISTRY ANT OTHER RESOURCES AVAILABLE THROUGH THE CTSA PROGRAM COLOCATEDDED IN 13 OF 14 IDDRCs AND ALSO IN THE PROCESS OF DEVELOPING ONE OR MORE USE CASES FOR ALL OF US. THESE GROUPS ARE VERY ACTIVE. IN MEETING THE GOALS OF DISSEMINATION FOR THIS PROGRAM, THESE IDDRCs ARE DEVELOPING JOINT PUBLICATIONS TO ENGAGE, LAY AND SCIENTIFIC AUDIENCES WITH INCREASING OUTREACH AND PUBLICITY AROUND DISCOVERIES BEING MADE. SO ESSENTIALLY IDDRCs ARE PLAYING A PART IN TRANSLATIONAL RESEARCH CYCLE THAT INVOLVES I THINK CONTINUUM BETWEEN BASIC SCIENCE OF CHARACTERIZATIONS ETIOLOGY, SOME OF THE GENOMICS APPROACHES IN OTHERS, DEVELOPING MODEL SYSTEMS INCLUDING CELL BASED AND ANIMAL SYSTEMS, IDENTIFYING POTENTIAL TARGETS THAT COULD BE VALIDATED COULD BE FOCUS OF PRE-CLINICAL TRIALS WHICH LEAD TO CLINICAL TRIALS AND THEN CONTINUE TO INFORM OUR UNDERSTANDING OF ETIOLOGY OF SOME OF THESE COMPLEX PHENOTYPES AND SO FORTH AND SO ON. SO WE'RE PLEASED WITH THE PROGRESS MADE BY IDDRC PROGRAM AND LOOK FORWARD TO MANY YEARS OF PROGRESS IN THAT DOMAIN. MY LAST FEW MINUTES I WANT TO TAKE A FEW MOMENTS TO TELL YOU ABOUT INCLUSION AND INFORMED CONSENT FOR PERSONS WITH INTELLECTUAL DISABILITIES. THIS IS A CAUSE CHAMPIONED BY DR. SHRIVER HERE AT PART OF OUR COUNCIL AND SOMETHING THAT WILL HAS BECOME VERY IMPORTANT TO THE INSTITUTE AS A WHOLE. DR. BIANCHI INTRODUCED YOU TO THE JAMA ONLINE PUBLICATION THAT WAS JUST RECENTLY RELEASED, LOOKING AT INCLUSION ACROSS THE LIFE SPAN. IN PARTICULAR THIS IS THE GRAPH FROM THAT PUBLICATION, I WANTED TO HIGHLIGHT INTELLECTUAL DISABILITY POPULATION. WHEN 338 DIFFERENT CLINICAL STUDIES PHASE 3 AND 4 STUDY WERE EVALUATED TO LOOK AT WHETHER OR NOT THEY EXPLICITLY EXCLUDED PERSONS WITH INTELLECTUAL DISABILITIES ONLY 12.4% EXCLUDED. BUT ONLY ONE OR TWO% INCLUDED. AND IN FACT THE VAST MAJORITY, WELL OVER 85% HAD NO MENTION WHETHER OR NOT PERSONS WITH INTELLECTUAL DISABILITIES WERE INCLUDED. WHAT THAT MEANS ESSENTIALLY IS FOR ALL PRACTICAL PURPOSES NOT INCLUDED IN RESEARCH STUDIES. WHY IS THAT IMPORTANT? NUMBER OF REASONS WHY IT'S SO IMPORTANT. FIRST, ALTERNATIVE DRUG DELIVERY METHODS ARE RARERY STUDIED BUT QUITE IMPORTANT FOR SOME PEOPLE WITH INTELLECTUAL DISABILITIES. WE ARE TALKING ABOUT THINGS SUCH AS GASTROSTOMY TUBES, RECTAL SUPPOSETORIES, FOR FOLKS DIFFICULTY WITH SWALLOWING OR FUNCTIONAL ABILITIES TO TAKE MEDICATIONS. THERE MAYBE LOWER THRESHOLD FOR TOXICITY IN SOME ID POPULATIONS. I THINK AN EXCELLENT EXAMPLE OF THIS, CHILDREN WITH DOWN SYNDROME 20 FOLD INCREASE RISK OF DEVELOPING ACUTE LEUKEMIA THAN THE GENERAL POPULATION BUT USE CONVENTIONAL CHEMOTHERAPEUTIC AGENTS THAT IS CYTOTOXIC FOR THESE CHILDREN AND CAN HAVE DRASTIC CONSEQUENCES. THERE'S LIMITED PHARMACOKINETICS AND PHARMACODYNAMIC STUDIES THAT MAY ALTER METABOLISM. THIS IS A HUGE AREA VERY LITTLE RESEARCH IS DONE. ONE ISSUE PROBLEM IS IRATE OF PSYCHOTROPIC AND OTHER MEDICATION PRESCRIPTION USE IN INTELLECTUAL DISABILITY POPULATION WITHOUT KNOWLEDGE OF UTILITY IN MANY CASES OR EVEN KNOWLEDGE OF ADVERSE ETCH EFFECTS. SINCE SOME ARE NON-VERBAL WE DON'T ALWAYS KNOW WHETHER OR NOT DRUGS ARE EFFECTIVE. SOMETIMES BEHAVIORAL CONS INVENTORIESES OCCUR THERE MAYBE CONDITION OF POLYPHARMACY WHERE MORE DRUGS ARE GIVEN TO AN INDIVIDUAL AND YOU DON'T KNOW WHETHER YOU'RE TREATING UNDERLYING CONDITION OR SIDE EFFECTS FROM PRIOR DRUG GIVEN. FINALLY IMPORTANT REASON TO INCLUDE PEOPLE WITH INTELLECTUAL DISABILITIES IN RESEARCH IS LEARN GENERALIZABLE RESEARCH ABOUT COMMON DISORDERS IN PEOPLE WITH IDD AT HIGHER OR LOWER RISK OF HAVING THOSE DISORDERS. SO FOR EXAMPLE, ADULTS WITH DOWN SYNDROME ARE HIGHER RISK OF DEVELOPING ALZHEIMERs DISEASE AND AT LOWER RISK OF DEVELOPING SOLID TUMORS. IF WE DO RESEARCH THAT INCLUDES INDIVIDUALS WE MIGHT BE ABLE TO CONFER INFORMATION THAT HELP US UNDERSTAND THE PATHOPHYSIOLOGY AND POTENTIAL TREATMENTS FOR THESE COMMON CONDITIONS. SO HERE IS A LIST OF BARRIERS USED TO EXCLUDE PEOPLE WITH IDD FROM RESEARCH. THESE ARE QUOTE UNQUOTE EXCUSES FOR NOT INCLUDING. SOMETIMES THERE ARE SCIENTIFIC REQUIREMENTS THAT MAY REQUIRE TYPICAL COGNITION OR MAYBE UNACCEPTABLE RISK THAT OUTWEIGH KNOWLEDGE TO BE GAINED BY STUDYING IDD POPULATION. THAT IS A LEGIT REASON TO EXCLUDE PEOPLE WITH CERTAIN TYPES OF RESEARCH. HOWEVER, SOMETIMES THE REASON IS USED IT'S TOO DIFFICULT FOR THEM TO PROVIDE INFORMED CONSENT. IT MAY TAKE MORE TIME TO PROVIDE CONSENT, MAYBE MORE DIFFICULT FOR THEM TO ENSURE UNDERSTANDING PARTICULARLY LOWER FUNCTIONING INDIVIDUALS, AND MAYBE HARDER TO OBTAIN PROXY CONSENT BY ENLISTING CAREGIVERS OR FAMILY MEMBERS TO PARTICIPATE. A SECOND REASON THAT'S RELATED IS MAYBE MORE DIFFICULT FOR INDIVIDUALS WITH IDD TO COMPLY WITH THE PROTOCOL. LOOK AT 300 RANDOMLY CHOSING CLINICAL TRIALS IN SIX HIGHERREST IMPACT MEDICAL JOURNALS OVER SIX YEARS AND ONLY 2% INCLUDED PERSONS WITH INTELLECTUAL DISABILITIES YET WHEN THEY LOOK IN DETAIL AT THE TOPICS, AND THE APPROACHES USED IN THOSE STUDIES, THEY FOUND AT LEAST 70% OF THOSE STUDIES COULD HAVE INCLUDED PEOPLE WITH INTELLECTUAL DISABILITIES WITH MINOR ACCOMMODATIONS OR MODIFICATIONS. WE ARE TALKING THINGS LIKE USING VISUAL AIDS, TO HELP WITH UNDERSTANDING INFORMED CONSENT, MAYBE EMPLOYING CAREGIVERS TO HELP WITH DRUG ADMINISTRATION THINGS SUCH AS USING ACCLIMATION PROTOCOLS AND MOCK SCANNERS TO DO MRI STUDIES. SO WHAT THIS THIS IS SAYING IS YES IT MAY TAKE MORE EFFORT BUT DIFFICULTIES IN PROVIDING INFORMED CONSENT COMPLYING WITH PROTOCOLS, MANY CASES ARE NOT LEGITIMATE TO EXCLUDE INDIVIDUALS FROM RESEARCH STUDIES. THEN FINALLY ONE OF THE CONCERNS IS ETHICAL ONE. THIS IS A VULNERABLE POPULATION, THERE'S CONCERN ABOUT COERCION FOR THIS POPULATION AND WE NEED TO PROTECT THEM BUT AS WE HAVE HEARD, WE ALSO NEED TO CONSIDER ISSUES OF SELF-DETERMINATION AND ISSUES OF RESPECT AND AUTONOMY WHICH ARE ALSO IMPORTANT IN THE POPULATION WITH INTELLECTUAL DISABILITIES. SO RATHER THAN EXCLUDING THEM WE NEED TO PROTECT THEM THROUGH RESEARCH RATHER THAN FROM RESEARCH. SO AGAIN THIS IS NOT A LEGITIMATE BARRIER. SO I WOULD LIKE TO REMIND YOU THE HISTORY OF INCLUSION AT NIH SPONSORED RESEARCH, IT STARTED REALLY IN THE 1980s WITH INCLUDING WOMEN IN RESEARCH STUDIES, THEN IN THE 19 -- IN THE EARLY 2000s RACIAL ETHNIC MINORITIES IN 2016 WE INCLUDED SEX AND GENDER MINORITIES AS HEALTH DISPARITY POPULATION AND MORE RECENTLY WE LOOK AT 2 #st CENTURY CURES ACT INCLUDING CHILDREN IN OLDER POPULATIONS AS WELL AS PREGNANT AND LACTATING WOMEN AND CHILDREN WITH DISABLES AS THEE IN FRONTIER. WHAT IS THE NEXT TO INCLUDE PEOPLE IN RESEARCH. FIRST WE HAVE SOME WEB TOOLS AND RESOURCES AVAILABLE ON NIH CLINICAL RESEARCH TRIALS IN YOU. THIS INCLUDES A LIST OF REGISTRIES FOR RARE AND COMMON CONDITIONS INCLUDING DS CONNECT AND OPERATION SOURCE, SOME OF THE REGISTRIES NICHD SPONSORS. THERE'S A TAB HERE THAT HAS VERY HELPFUL INFORMATION AND LITTLE VIDEO CLIPS FOR PARENTS AND CHILDREN CONSIDERING PARTICIPATING IN RESEARCH. AND CLINICALTRIALS.GOV HAS QUITE A BIT OF INFORMATION ABOUT CLINICAL TRIALS. MORE SPECIFICALLY HERE AT NICHD YOU HEARD ABOUT THE # 1st SENTENCERY -- 2 #st CENTURY CURESES ACT AND EFFORTS TO INCLUDE PEOPLE ACROSS THE LIFE SPAN WITH POLICY ANNOUNCED IN DECEMBER OF THIS PAST YEAR. NICHD CONTINUES TO WORK WITH ALL OF US LEADERSHIP TO INCLUDE PEOPLE'S INTELLECTUAL DISABILITIES INITIATIVE AND ALISON HAS BEEN INVOLVED IN THIS, APPARENTLY INTELLECTUAL DISABILITIES IS INCLUDED AND THERE'S HOPE CHILDREN WILL ALSO BE INCLUDED STARTING AT LAUNCH THIS SPRING. THE TRANS-NIH DOWN SYNDROME WORKING GROUP WHICH COMPRISES 11 INSTITUTES AND CENTERS ACROSS NIH IS TAKING THE CHARGE IN TRYING TO DEVELOP MORE TOOLS AND DISCUSSION AROUND INCLUSION AND BROADER SCALE FOR INTELLECTUAL DISABILITIES AND CLINICAL RESEARCH. WE'RE TRYING TO ENSURE WE ENGAGE STAKEHOLDERS INCLUDING FAMILIES IN THOSE WITH IDDs SO LIKE TO CLOSE WITH THIS QUOTE WHICH ACTUALLY HAD ITS ORIGINS IN THE 1500s IN CENTRAL EUROPE BELIEVE IT OR NOT BUT CHAMPIONED BY DISABILITY COMMUNITY IN THE 1990s. NOTHING ABOUT US WITHOUT US. FINALLY I WOULD LIKE TO THANK MY COLLEAGUES IN THE IDD BRANCH WHO ARE DOING ALL THE IMPORTANT WORK I HAVE DESCRIBED TO YOU, NICHD COLLEAGUES AND THEN FELLOW PRESENTERS YOU WILL HEAR FROM IN A MOMENT, DR. STEPHANIE SHERMAN, DAVID E GRAND AND HIS MOTHER KATHLEEN AND MANY PATIENT ADVOCACY GROUPS AND FAMILY ORGANIZATIONS. THANK YOU. [APPLAUSE] >> ANY QUESTIONS FOR MELISSA? >> EXCELLENT PRESENTATION. THE THINGS I'M CONCERNED ABOUT IS THE TRANSLATION OF THIS INTO THE CLINIC. >> PEDIATRICS PUBLISHED A NUMBER OF PAPERS ABOUT THE YIELD FROM WHOLE EXOME SEQUENCING. REALLY VERY HIGH. YET MY PERCEPTION IS THAT IT'S NOT ROUTINELY DONE. DESPITE THE FACT IT'S CHEEP. ONE PAPER PUBLISHED TALKED DIAGNOSTIC ODYSSEY OF CHILDREN THAT DON'T HAVE DIAGNOSIS H. LIKE SEVEN YEARS BEFORE THEY GET WHOLE EXOSOME SEQUENCING DONE AND DIAGNOSIS MADE. WHAT I WOULD LIKE TO KNOW IS WHAT IS NIH, NICHD DOING IN PARTICULAR TOE TRY TO MOVE THIS TO THE CLINIC AND DECREASE THAT LAG WE SEE SO MANY OTHER SCIENTIFIC DISCOVERY? >> COUPLE OF THOUGHTS COME TO MIND, ONE OF THE PROGRAMS THAT I HAVEN'T TALKED ABOUT WHICH IS TRANS-NIH IS UNDIAGNOSED DISEASES NETWORK, UNDIAGNOSED DISEASES PROGRAM. WHAT THIS IS TRYING TO CREATE I THINK CENTERS THROUGHOUT THE COUNTRY FOCUSING ON INDIVIDUALS NOT PREVIOUSLY DIAGNOSED AND ARE USING MANY OF THESE GENOMIC APPROACHES TO HELP WITH DIAGNOSIS. AND I THINK AS YOU START TO ROLE THOSE OUT INTO SOME OF THE ACADEMIC CENTERS IN THE COUNTRY. THAT BECOMES STANDARD OF CARE. THE NUMBER OF DIAGNOSES MADE THROUGH THAT PROGRAM HAS REALLY INCREASED GENERALIZABLE KNOWLEDGE. TO THE EXTENT THAT I THINK THIS WILL BECOME STANDARD PRACTICE. THIS IS NOT NECESSARILY AN NIH ACTIVITY BUT I'M ON THE AAP COUNCIL IN GENETICS AND ONE THING WE LOOK AT IS REVISING RECOMMENDATIONS FROM THE AAP IN TERMS OF APPROACH TO THE CHILD WITH INTELLECTUAL DISABILITIES AND I THINK MAKING SOME OF THESE RECOMMENDATIONS, CLINICAL PRACTICE WILL ALSO GO A LONG WAY IN INCREASING THE UPTAKE OF THESE TESTING PARADIGMS INTO THE CLINICAL SETTING. >> I THOUGHT THAT WAS GOING TO BE A SOFTBALL FOR YOU TO ADVERTISE THE WORKSHOP AS WELL. I CAN CERTAINLY SAY SOMETHING ABOUT THAT. I WAS THINKING AFTER BIRTH, BUT WE'RE ALSO PROMOTING AND DEVELOPING IN CONJUNCTION WITH OUR COLLEAGUES AT NHGRI A WORKSHOP THAT'S GOING TO BE LOOKING AT GENOMIC HEALTHCARE IN EARLIER SETTINGS THAN THE NEWBORN PERIOD LOOKING AT PRECONCEPTION REPRODUCTION, REPRODUCTIVE PERIOD, THE PRENATAL AND NEONATAL TIME FRAME. AND TRYING TO DETERMINE WHETHER OR NOT THERE'S A ROLE, WE THINK THERE'S LIKELY A ROLE FOR GENOMIC APPROACHES IN THESE TIME FRAMES AND HOW THAT IMPACT CLINICAL OUTCOMES AND EARLIER DIAGNOSES FOR THESE INDIVIDUALS. >> BACK TO WHAT YOU WERE SAYING ABOUT BARRIERS. I THINK YOU NAILED IT WHEN YOU SAID EXCUSES. OF NOT INCLUDING PERSONS WITH INTELLECTUAL DISABILITIES. ONE OF THE BULLET POINTS YOU HAD WAS INABILITY TO PROVIDE INFORMED CONSENT AND YOU HAVE MAY, MAY. DID THEY SAY WERE THEY ASSUMING OR DID THEY TRY TO GET? >> YOU'RE TALKING THAT PAPER I DESCRIBE? WHAT THAT PAPER DID IS A RETROACTIVE LOOK AT THOSE STUDIES THAT HAD ALREADY BEEN SURVEYED SO THEY WENT BACK AND CONTACTED THE PIs TRIED TO FIGURE OUT WHETHER THEY COULD HAVE INCLUDED PERSONS WITH INTELLECTUAL DISABILITIES. OVER 70% OF THE TIME THEY COULD HAVE WITH RELATIVELY MINOR ACCOMMODATIONS. SO THAT WAS MY LANGUAGE TO INTERPRET THE RESULTS RESULTS OF THAT PARTICULAR STUDY. >> THANK YOU, MELISSA, EXCELLENT PRESENTATION AND FOR THIS TIME. I WOULD LIKE TO SUGGEST, DR. BIANCHI WE DEDICATE MORE TIME TO THIS TOPIC IN THE FUTURE. I THINK THE WAY IN WHICH MELISSA, YOU HAVE PRESENTED THE CLEAR INEXCUSABLE NATURE OF THE DISCRIMINATION AGAINST THIS POPULATION NOT JUST NIH BUT LARGER SCIENTIFIC ENTERPRISE,NESS SUGGEST NEED FOR US TOW DO A DEEPER DIVE WHERE THAT RESISTANCE LIES AND WHAT WE REALLY NEED TO DO TO OVERCOME IT. BECAUSE IT'S NOT ACCEPTABLE THAT AT 50 YEARS AFTER THE FOUNDATION OF THE IDDRCs, THAT WE'RE NOW ADDRESSING THIS ISSUE. IT'S A REFERENDUM ON ALL OF US SO THERE'S DEEP RESISTANCE OBVIOUSLY, YOU'RE RIGHT IT'S UNACCEPTABLE BUT IT'S THERE. IT'S VERY PERSISTENT AND NOT GOING TO GO DOWN WITHOUT A FIGHT. SO I JUST WOULD LIKE TO ACKNOWLEDGE THAT THIS IS THE FIRST -- I WOULD LIKE TO SEE THIS AS THE FIRST PRESENTATION OF A LONGER DISCUSSION BECAUSE OF THE CENTRAL NATURE OF THIS INSTITUTES'S RESPONSIBILITY TO BE NOT JUST A FUNDER BUT ADVOCATE. WE HAVE TO ADDRESS THE ADVOCACY NATURE WITHIN THE SCIENTIFIC ENTERPRISE AND SUBSEQUENT DISCUSSION. >> THANK YOU FOR YOUR COMMENTS, WELL NOTED. CONTINUING THE THEME WE'RE GOING THE NEXT HEAR FROM DR. STEPHANIE SHERMAN. AN INVESTIGATOR WHOSE WORK IS FUNDED BY NICHD. PROFESSOR OF HUMAN GENETICS EMORY UNIVERSITY ATLANTA. DR. SHERMAN'S TRAINING IS GENETIC EPIDEMIOLOGY. SHE'S LED THE COORDINATION OF MULTI-SIGHT PROJECTS TO ENROLL -- UNRAVEL THE GENETIC ARCHITECTURE OF COMPLEX TRAITS AND TO UNDERSTAND POTENTIAL GENE ENVIRONMENTAL INTERACTIONS IN MULTIPLE HUMAN GENETIC DISEASES. CURRENTLY DR. SHERMAN IS INVOLVED IN RESEARCH TO UNDERSTAND THE CAUSES AND CONSEQUENCES OF DOWN'S SYNDROME TRISOMY 21. SHE'S CO-DIRECTOR OF DOWN SYNDROME CENTER AT EMORY UIVERSITY, A CENTER THAT COMBINES CLINICAL CARE, CLINICAL TRIALS AND RESEARCH AND EDUCATION RELATED THE DOWN'S SYNDROME. SHE ALSO DOES RESEARCH IN A NUMBER OF OTHER AREAS OF INTELLECTUAL DISABILITY INCLUDING FRAGILE X. SHE ALSO TRAINS GRADUATE STUDENTS AND POST-DOCTORAL FELLOWS IN GENETIC EPIDEMIOLOGY. PLEASE HELP ME WELCOME DR. STEPHANIE SHERMAN. [APPLAUSE] >> THANK YOU VERY MUCH. I WANT TO FIRST THANK MELISSA FOR SETTING UP THIS WHOLE TALK THAT I'LL BE GIVING WHERE SHE HAS DESCRIBED THE CHALLENGES OF DOING RESEARCH IN INTELLECTUAL DISABILITIES. WHAT I'M GOING TO FOCUS ON REALLY IS THE PARTNERSHIPS THAT WE FORM BETWEEN THE INDIVIDUALS WITH INTELLECTUAL DISABILITIES OR FAMILIES CLINICIANS AND SCIENTISTS TO TRY TO MOVE TOWARDS THIS IDEA OF BRINGING PRECISION MEDICINE TO PEOPLE WITH INTELLECTUAL DISABILITIES. I'M GOING TO USE TWO GENETIC DISORDERS OR TWO CONDITIONS TO EXPLAIN THESE TWO PHENOMENON THAT I THINK ARE TRUE. NUMBER ONE, PEOPLE WITH INTELLECTUAL AND DEVELOPMENTAL DISABILITIES AND THEIR FAMILIES HAVE LED THE WAY TOWARDS PRECISION MEDICINE WAY BEFORE WE EVEN HAD THAT TERM. AND THEN THE NEXT ONE IS, I'LL USE HISTORICAL PRESENTATION FOR THAT OR POINT OF VIEW. NEXT IS THAT THIS IS THE POINT, YOU HAVE HEARD ALL THE ISSUES THAT HAVE BEEN BROUGHT UP ABOUT INCLUSION THAT NOW MORE THAN EVER IN ORDER TO BRING PRECISION MEDICINE TO INDIVIDUALS WITH DISABILITIES A LOT OF HELP IS NEEDEDDED IN THESE PARTNERSHIPS. FOR THIS I WILL TALK A LITTLE BIT ABOUT RESEARCH PROGRAM AND EFFORTS TOWARDS THIS BUT ALSO EMPHASIZE THE NATIONAL INTERNATIONAL EFFORTS REALLY TRYING TO BRING PRECISION MEDICINE IN A MEANINGFUL WAY SO I OOH HE WILL USE FRAGILE X AND DOWN SYNDROME AS TWO CONDITIONS TO EMPHASIZE THESE POINTS. SO FIRST HISTORICAL POINT OF VIEW. IN THE PAST ALL INDIVIDUALS WITH INTELLECTUAL AND DEVELOPMENTAL DISABILITIES JUST GOING TO PULL TOGETHER. THAT'S ABOUT AS CLEARLY DEFINED AS THINGS WERE. FOR DOWN SYNDROME, IT HAD INTERESTING IN THE MID 1800s MANY CLINICS STARTED TO DEFINE OR UNDERSTAND THAT THERE WAS A GROUP OF INDIVIDUALS THAT HAD SHORT STATURE AND CHARACTERISTIC FACIAL FEATURES WE HAVE COME TO CALL DOWN SYNDROME. WHERE WE NEED TO REALLY THANK JOHN LANGDON FOR THE CONDITION RECEIVED ITS NAME IS THAT HE EMPHASIZED NOW LET'S TAKE THIS GROUP OF INDIVIDUALS AND CONSIDER THEM BY THEMSELVES AS AN ENTITY, AND THEN MOVE ON FROM THERE TO UNDERSTAND WHAT IS THE BASIS OF THIS CONDITION. SO THAT WAS THE FIRST EFFORT AND ONCE THAT WAS DONE THERE WAS MANY INDIVIDUALS THAT WERE CONTRIBUTING TO UNDERSTAND THE ETIOLOGICAL BASE OF THIS CONDITION SO (INAUDIBLE) WAS ONE OF FIRST AND THERE WAS MANY THAT PRECEDED HIM THAT NOTED THE FIRST RISK FACTOR THAT WAS ASSOCIATED WITH THIS CONDITION AND THAT BEING THE INCREASE PARENTAL AGE. PENROSE DEFINED THAT IT WASN'T THE FATHER'S AGE OR PARODY, IT WAS MOTHER'S AGE THAT INCREASED THE FREQUENCY OF THIS PARTICULAR DISORDER. HE ALSO LATER ON IN THE 50s IF THIS WAS A GRAPH FROM HIS PAPER THIS IS THE AGE OF THE MOTHER AT BIRTH OF CHILD WITH DOWN'S SYNDROME, HE SHOWED THAT THIS IS A NORMAL DISTRIBUTION OF AGE, NOT JUST SHIFTED TO THE HIGHER YEARS. THERE'S EASILY SEEN TWO UNDERLYING DISTRIBUTIONS. CALL THE -- I LOVE THIS PICTURE. THE SPHINX CURVE. HE THEN PROPOSED NOT JUST ONE MECHANISM LEADING TO DOWN SYNDROME BUT SEVERAL SO THAT WAS HIS ANOTHER MAJOR CONTRIBUTION. AT ADVENT OF KARYOTYPEING THE TRENCH GROUP DR. GO SAY IDENTIFIED THREE STANDING CELLSOME 21EST THAT LED TO DOWN SYNDROME, CONFIRMED BY DR. JACOBS THE SAME YEAR AND DR. PALANI SAID THIS IS THANK YOU TO TRANSLOCATION, THERE'S CHROMOSOME 21 ATTACHED TO CHROMOSOME 14. SO ANOTHER MECHANISM. SO WE KNOW ABOUT 95% OVERWHELMING MAJORITY OF INDIVIDUALS WITH DOWN SYNDROME HAVE EXCHROMOSOME # 1 DUE TO ERROR THAT OCCURS DURING FORMATION OF GAMETES. AND A SMALL PERCENTAGE HAVE TWO CELL LINES, ONE WITH EXTRA CHROMOSOME 21, ONE WITH NORMAL 1% AND 4% HAVE TRANSLOCATION CARO TYPE. KARYOTYPE. TRY FOG GO FROM ETIOLOGICAL BASED DIAGNOSIS TO MECHANISTIC BASED DIAGNOSIS WHERE YOU CAN SAY FOR EXAMPLE TAKING THIS GROUP OF INDIVIDUALS AND SPLITTING THEM INTO TWO GROUPS, THOSE IN WHICH THE ERROR OCCURRED IN THE EGG, OO SITE AND THOSE THAT OCCURRED IN THE SPERM. YOU CAN GO FURTHER THAN THAT AND ASK WHEN IN MYOSIS DID THESE ERRORS OCCUR, AT THE BEGINNING OR END OF MYOSIS? WHY IS IT IMPORTANT? IT MIGHT START TO AFFECT WHAT -- FIRST YOU CAN BEGIN TO ASK WHAT THE POTENTIAL FACTORS IN THE WOMAN MAY HAVE LED TO THESE ERRORS THAT OCCURRED IN THE EGG. SEPARATING OUT THESE. THEN YOU CAN ASK DO THESE DIFFERENT TYPES OF ERRORS AFFECT OUTCOME. SO AGAIN WE CAN GO STRAIGHT FROM JUST A GENERAL INCLUDING EVERYBODY AS -- WITH PARTICULAR PHENOTYPE ALL THE WAY UP TO PULLING OUT SPECIFIC MECHANISTIC GROUPS TO HELP FORWARD IDENTIFY ING FACTORS RELATED TO THE PARTICULAR CONDITION. SAME FOR FRAGILE X SYNDROME THOUGH LATER HISTORY. THIS -- EARLYNAL -- EARLY ON IT WAS NOTED THERE HAD'S MANY MORE MALES IN INSTITUTIONS FOR THOSE WITH INTELLECTUAL DISABILITIES THAN FEMALES. IN THE BEGINNING PENROSE SAID THIS IS BIAS, THIS IS MORE SURVEY LENT OF MALES. WE'RE MUCH MORE WORRIED ABOUT THEIR INTELLECTUAL DISABILITY WHERE GIRLS CAN STAY AT HOME AND DO WHATEVER AND IT DOESN'T MATTER. BUT FINALLY IN THE 60s, DR. LURKY ARGUED CONVINCINGLY THAT MAYBE THIS ISN'T JUST DUE TO A BIAS, THIS IS DUE TO GENES ON THE X CHROMOSOME SO HE CONSIDERED LOOKING AT X LINKED PEDIGREES WITH OBVIOUS PATTERN OF INHERITANCE. AND THOSE WITH NO OBVIOUS CLINICAL TRAITS. THIS WAS SUPPORTED BY JILL TURNER IN THE '70s SO THIS BECAME A PHENOTYPIC GROUP THAT HELPED DISTINGUISH THIS GROUP OF INDIVIDUALS FROM THE GENERAL INTELLECTUAL DISABILITY. LATER ON IN THE LATE '60s AND THEN GAP IN TIME TO '77 THERE WAS A PARTICULAR CYTOGENETIC MARKER UNDER PARTICULAR CULTURE SYSTEM THAT APPEARED IN INDIVIDUALS, MALES SPECIFICALLY, THAT HAD INTELLECTUAL DISABILITY. INFORMATION CONNECTED WITH MALES WHO HAD MEDICAL ORGANISMS, EXCELLENT INHERITANCE, MICROORGANISM IN THE CYTOGENETIC MARKER. ORIGINALLY CALLED MARKER X BUT LATER ON FRAGILE X. ONCE YOU HAD THIS GROUP OF INDIVIDUALS POOLED OUT OF ALL THE REST YOU CAN SEE COMMON FEATURES. FOR EXAMPLE YOU CAN SEE COMMON FACIAL FEATURES. THE LARGER EARS, PROTRUDING IN MOST CASES THE LONG FACE T SQUARE JAW. ONCE YOU HAVE A PARTICULAR HOMOGENOUS GROUP YOU CAN ASK IMPORTANT QUESTIONS. THEN LATER IN THE EARLY '90s THIS PARTICULAR MARKER IN THESE VEGES WAS UNDERLYING -- INDIVIDUALS WAS UNDERLYING IT LONGCAL BASIS OF THIS WAS EXPANDED REPEAT DISORDERS, IN THIS CASE CGG REPEAT. CALLED THE FRAGILE X SYNDROME, HERE IS AN EXAMPLE, YOU CAN SEE THOSE WHO WERE AFFECTED WITH FRAGILE X SYNDROME HAD HIGHER IN PERSON THAT YOU CANNOT SEE IN NORMALS AND IT WAS EXPANDED REPEAT THAT LEADS TO SILENCING OF THIS PARTICULAR GENE. THIS IS JUST ONE GROUP. INVOLVED IN THAT DISCOVERY ALONG WITH TWO OTHERS. NOW I WILL SKIP ALL THE BASIC SCIENCE AND ALL THE WONDERFUL MODEL SYSTEMS BUILT AND USED TO REALLY UNDERSTAND THE FUNCTION OF THIS PARTICULAR GENE OR THE FUNCTION OF GENES ON CHROMOSOME 21 INCREASED IN IN DOSAGE AND HOW THEY LEAD TO MISREGULATION AND TALK ABOUT ARE WE DONE NOW, WE HAVE A DIAGNOSIS, WE HAVE THE MECHANISM, ARE WE DONE? HAVE WE REACHED THE GOAL OF PRECISION MEDICINE TO TREAT INDIVIDUALS. I WOULD ARGUE AND I THINK EVERYBODY IN THIS ROOM WOULD ARGUE NO. FOR EXAMPLE IN DOWN'S SYNDROME, THE SECOND SPECTRUM OF OUTCOME IS EXTREMELY VARIABLE BIRTH DEFECTS. 50% OF INDIVIDUALS WITH DOWN SYNDROME HAVE A SIGNIFICANT CONGENITAL HEART DEFECT. 50% HAVE STRUCTURALLY NORMAL HEARTS. THEY ALL HAVE THREE CHROMOSOME 21s, WHAT CAUSES THIS DIFFERENCE. IN TERMS OF COGNITION AND BEHAVIOR, YOU CAN -- IF YOU LOOK AT THE DISTRIBUTION OF LEVEL OF COGNITION IT VARIES TREMENDOUSLY. SEIZURES PRESENT IN SOME NOT OTHERS, LANGUAGE DEVELOPMENT IS PRESENT IN SOME, OTHERS ARE NON-VERBAL. AUTISM IS A HIGHER DIAGNOSTIC COMORBIDITY AMONG INDIVIDUALS WITH DOWN SYNDROME AND WHY. LASTLY AS WE HEARD AGING PROCESS IN INDIVIDUALS WITH X CHROMOSOME 21 DIFFERS WHERE THERE'S INCREASE FOR ALZHEIMER'S DISEASE, THIS IS NOT UNDERSTOOD WHEN THERE IS TREMENDOUS VARIATION IN ONSET OF DISEASE. WE CAN DO THE SAME THING WITH FRAGILE X THOUGH NOT MEDICAL COMPLICATIONS YOU CAN SEE SIGNIFICANT VARIATION IN TERMS OF THE OUTCOME RELATED TO COGNITION SAND BEHAVIOR. WE ARE STARTING TO SEE THAT AS EXPECTED FOR EVERYONE THERE'S DIFFERENCES IN DRUG RESPONSES. SO ALL THIS UNDERLYING VARIATION HAS TO BE UNDERSTOOD IN ORDER TO BRING PRECISION MEDICINE TO THESE GROUPS OF INDIVIDUALS. WHAT CONTRIBUTES TO THE VARIATION IN CLINICAL OUTCOMES? IT'S CLEARLY THE ENVIRONMENT, SEQUENCE, DNA AND I LOVE THIS ROLE OF THE DICE, STOCHASTIC EFFECTS OR RANDOM EFFECTS. I WOULD CALL THOSE EFFECTS WE DON'T KNOW HOW TO DEFINE YET. THESE ARE NOT RANDOM. WE JUST NEED TO UPS WHAT THEY ARE. NOW WITH BRINGING -- WHAT THIS TAKES TO UNDERSTAND WHAT IS VARIATION AND THEIR OUTCOME, WHAT IS VARIATION OUTCOMES AND THE CAUSES OF THAT, REALLY MEANS BRINGING TOGETHER LARGE COHORTS OF INDIVIDUALS TO STUDY THIS VARIATION. I THINK WE HAVE TOOLS. WE HAVE TOOLS TO DO ALL THESE OMICS ON THESE INDIVIDUALS. WE JUST NEED THAT PARTNERSHIP WITH LARGE COHORTS AND FUNDING. SO ONE STRATEGY,S IN WHAT WE HAVE TAKEN, TO COMPARE THE EXTREMES OF THE SIGNIFICANT CLINICAL OUTCOME OF INTEREST AMONG THOSE WITH THE SAME GENETIC DISORDER. IN ORDER TO IDENTIFY THOSE ENVIRONMENTAL FACTORS OR GENETIC FACTORS THAT LEAD TO AFFECTED BIOLOGICAL PATHWAYS. ONCE THIS IS DEFINED YOU CAN START TO LOOK AT WHAT THE INTERVENTIONS ARE THAT MIGHT SPECIFICALLY TARGET THAT GENETIC DISORDER. WE HAVE DONE THIS FOR DOWN SYNDROME IN SEVERAL WAYS, AN EXAMPLE IN COGNITION, WE CAN DO A TEST BATTERY TO LOOK AT DOMAINS TO ASK WHO ARE LOW PERFORMERS AND WHO ARE HIGH PERFORMERS AND THEN GO THROUGH THIS PROCESS OF IDENTIFYING RELATED FACTORS. AGAIN WITH TARGET TRYING TO FIND INTERVENTIONS TO EQUALIZE THAT, PUT BACK THE BALANCE OF AFFECTED PATHWAY. HOW HAVE WE AND OTHERS DONE THIS? WHAT WE HAVE DONE IS TAKEN PROJECTS INVOLVED IN DOWN SYNDROME AND COMBINED INTO WHAT WE CALL DOWN SYNDROME 360. SETTING A FOUNDATION FOR GENOTYPE PHENOTYPE PROJECT MOVES TOWARD PRECISION MEDICINE. WE HAVE TAKEN THE THREE PROJECTS WE HAVE DONE OVER THE YEARS AND THEN WITH FUNDING FROM NICHD, NHLBI AND FROM SUPPORT FOR THIS COGNITION PROJECT FROM THE DOWN SYNDROME RESEARCH FOUNDATION, WE HAVE BEEN ABLE TO DEVELOP A CLINICAL REPOSITORY AS WELL AS BIOLOGICAL REPOSITORY OF SAMPLES ENGAGING ABOUT 2800 INDIVIDUALS WITH DOWN SYNDROME OVER THE TIME. NOW WE HAVE THIS MANY RESOURCES CELL LINES DNA SAMPLES IN THE INVENTORY NOW LEFT OVER FROM GENOTYPING SEQUENCING WE HAVE DONE, WE HAVE USED CORE SERVICES OF NICHD TO GENOTYPE 800 TRIOS IN THIS COHORT WE HAVE USED NHLBI SERVICES TO DO WHOLE EXOSOME SEQUENCING IN THIS COHORT AND ALL THESE DATA CAN THEN BE APPLIED TO DOWN SYNDROME COGNITION PROJECT HERE. WE HAVE 300 PEOPLE WHO WE HAVE DONE DEEP PHENOTYPING. AND I WANT TO ACKNOWLEDGE ALSO ROGER LEAVES, WHO IS PART OF THE STUDIES. SO WHAT CAN I SHOW? WHAT VALUE IF WE HAVE SOME METRICS TO SAY IS THIS PROGRAM GOING TO WORK WHAT PROGRAM IS TRYING TO LOOK AT DOWN SYNDROME IN DEEP WAY IN TERMS OF PHENOTYPING. WHAT -- HAVE THERE BEEN CONTRIBUTIONS? AND YES, I WOULD SAY SEVERAL WAYS. BECAUSE OF RESEARCH WE HAVE DONE WE HAVE HAD TEN SITES WHO CONTRIBUTED AND SET UP THEIR CLINICS FOR RESEARCH OF THIS TYPE. SO I WOULD SAY THAT WE HAVE NOW AT LEAST TEN CLINICAL RESEARCH READY SITES THAT WERE TRAINED THROUGH THIS PARTICULAR PROJECT THAT COULD GET MORE INVOLVED IN CLINICAL TRIALS. WE HAVE THREE IN RED ACTIVE NOW BECAUSE LIMITED FUNDING SHOW WE ENGAGE THE NATIONAL DOWN SYNDROME SOCIETY TO HELP FUND SOME OF THE TESTING OF INDIVIDUALS SO WE SET UP DOWN SYNDROME RESEARCH AWARENESS WEEK TO GO TO DIFFERENT CITIES AND INVITE THE FAMILIES AND PARTICIPANTS TO UNDERSTAND WHAT IS VALUE OF RESEARCH TAKING PART IN RESEARCH AND HOW CAN THEY DO IT AND HOW CAN WE DEVELOP PARTNERSHIP AND IN FACT INDIVIDUALS FROM THIS ALSO BEEN PART OF THOSE RESEARCH AWARENESS WEEKENDS. ALSO OUTCOME MEASURES DEVELOPED THROUGH THE DOWN SYNDROME COGNITION PROJECT, HAVE BEEN USED TO DEVELOP OUTCOMES FOR CLINICAL TRIALS. INDIVIDUALS WHO TOOK PART IN STUDIES, TEST RETEST STUDIES TO SUPPORT OUTCOME MEASURES FOR CLINICAL TRIALS. THROUGH THE DOWN SYNDROME 21 RESEARCH SOCIETY THIS IS AN INTERNATIONAL CONSORTIUM, WORKING WITH THEIR COMMITTEE TO AGAIN CREATE A CORE BATTERY THAT CAN BE USED INTERNATIONALLY TO DEVELOP A LARGE COHORT OF INDIVIDUALS WITH DOWN SYNDROME. PARTICIPATING IN DATA HARMONIZATION. LASTLY AS AN EXAMPLE, THIS RESOURCE OR ANY RESOURCE SUCH AS THIS, CAN CONTRIBUTE TO OTHER PROJECTS SO THE DATA THAT WE HAVE DONE ALL OUR GENOMIC DATA HAS GONE TO THREE GROUPS STUDYING DOWN SYNDROME ASSOCIATED DOWN SYNDROME CANCERS. THE COGNITIVE DATA IS GOING TO BE USED FOR THE CONTROL DATA, FOR LOOKING AT ADVERSE EFFECTS OF CANCER TREATMENT IN INDIVIDUALS WITH DOWN SYNDROME. AND LASTLY WE CAN USE THE CELL LINES FOR MANY THINGS. IN ONE CASE TO THE BOSTON GROUP LOOKING AT GENOMIC STABILITY IN CELLS WITH EXTRA CHROMOSOME 21. SO MANY CONTRIBUTIONS HAPPENING IMMEDIATELY ONCE YOU CAN BRING ENTITIES TOGETHER. OTHER WAY OF EXPANDING, WE'RE NOW REACHING OUT TO OTHER INTERNATIONAL GROUPS WHO HAVE LARGE COHORTS AND HOPEFULLY GET THIS TOGETHER TO AGAIN EXPAND THE RESOURCE FOR NEEDED SAMPLE SIZE FOR THESE STUDIES. WE USE EXISTING INFRASTRUCTURES IN SERVICES WHICH IMPORTANT. HIGHLIGHT DOWN SYNDROME CONNECT FOR A SECOND. THIS IS A LAUNCHED IN 2003. THIS IS AN NIH INITIATIVE, WHICH A REGISTRY FOR INDIVIDUALS WITH DOWN SYNDROME. HERE IS A PICTURE FROM THE WEB PAGE, THE TARGET IS ABOUT 10,000, UP TO ALMOST 4,000 INDIVIDUALS NOW WHO HAVE REGISTERED. THIS IS A WAY TO FACILITATE CLINICAL RESEARCH. HERE ARE THE MODULES THAT ARE PARENTS AND SELF-ADVOCATES EXPLORE ON SO ANALYZE DEIDENTIFIED DATA TO UNDERSTAND NATURAL HISTORY OF DOWN SYNDROME. SO IT'S A -- EVER GET A CHANCE, IT'S A NICE SOFTWARE WE CAN GO IN ANDEN PERUSE DATA IN ORDER TO GET PRELIMINARY INFORMATION ABOUT PARTICULAR OUTCOMES. FOR EXAMPLE HOW MANY PARTICIPANTS HAVE HAD CARDIAC OR HEART SURGERY. YOU CAN SEE THE NUMBERS HERE WITH NICE GRAPHIC REPRESENTATION. THE RESEARCH ADVISORY APPLICATION COMMITTEE HAS REVIEWED MANY DIFFERENT PROJECTS THAT HAVE PETITIONED TO USE THE DATA OR GET THE HELP TO RECRUIT INDIVIDUALS THROUGH DOWN SYNDROME CONNECT. I JUST LISTED A LOT, WON'T GO THROUGH IN DETAIL. I DO NEED TO GIVE A SHOUT OUT TO BOTH SUE JETTA AND MELISSA. THEY'RE ONES SO INVOLVED IN THAT DEVELOPMENT OF THIS BUT THEY REALLY DO FACILITATE RESEARCH, THEY GET ON THE PHONE WITH EVERY INVESTIGATOR AND SEE AND JUST WORK TO MAKE SURE THAT THEY CAN GET ACCESS AND GET THEIR RESEARCH DONE. SO IT'S AN IMPRESSSIVE TEAM. SO GOING BACK, WE HAVE WORKED WITH THE PEDIATRIC CARDIOLOGY -- CARDIAC GENOMICS CONSORTIUM WHICH LOOKS AT HEART DEFECTS IN WONDERFULLY THEY DID COLLECT DATA ON INDIVIDUALS WITH DOWN SYNDROME BUT NEVER ANALYZED IT SO WE WERE ABLE TO COMPLIMENT THEIR WORK. WORKING WITH THE CLINICAL TRANSLATIONAL SCIENCE INSTITUTES. LASTLY I MENTIONED THE T 21 RS INTERNATIONAL DOWN SYNDROME SOCIETY AND THIS IS WHERE WE'RE PUSHING TO HAVE INTERNATIONAL CONSORTIUM TO BRING RESOURCES TOGETHER. IT TAKES THE FAMILIES, IT TAKES PARTICIPANTS AND IT TAKES A LOT OF WORK, COULDN'T DO THIS WITHOUT THEM PARTICIPATING IN THESE KINDS OF KINDS OF RESEARCH TO BRING PRECISION MEDICINE. I CAN DO THE SAME FOR FRAGILE X SYNDROME, I'LL DO IT SHORTER HERE, IT'S A DIFFERENT TAKE AT THIS POINT. AGAIN, DIFFERENT CULTURE OF THE SCIENCE. WHAT HAS BEEN REALLY IMPORTANT IS NIH SUPPORT OF SENATORS -- OF CENTERS FOR COLLABORATIVE RESEARCH IN FRAGILE X, OVER SEVERAL YEARS NOW, CURRENTLY THERE'S THREE CENTERS THAT ARE INVOLVED RESEARCH, EACH TAKING A TACT TOWARD FRAGILE X SYNDROME AND ASSOCIATED DISORDERS PART OF THIS CENTER AT EMORY. OUR ASPECT IS AGAIN TO LOOK AT MODIFIERS FOR FRAGILE X DISORDER WE CALL FAX MOD SO WE'RE TRYING TO AGAIN UNDERSTAND THOSE GENES THAT MODIFY THE OUTCOME AND REED TO LEAD TO INCREASE SEVERITY TO TAKE THAT PARADIGM TO UNDERSTAND ARE THERE PARTICULAR IMBALANCES WE MIGHT TARGET TO BALANCE. SO WE HAVE A PROJECT LOOK AT THOSE WITH NO SEIZURES, THOSE WITH SEIZURES ALL WITH FRAGILE X SYNDROME TO UNDERSTAND WHAT THOSE MODIFYING FACTORS ARE. WHOLE GENOME SEQUENCING. MELISSA TALKED ABOUT PROBLEMS OF THIS, SO WE USE ALL THE BIOINFORMATIC TOOLS TO RANK VARIANT SEEM TO BE INVOLVED IN PRESENCE OF SEIZURE AND USE A FLY MODEL SYSTEM TO DOCUMENT SECOND INTERMEDIATE SCREEN ESSENTIALLY TO WHOLE ORGANISM FUNCTIONAL SCREEN TO SEE IF VARIANT WE IDENTIFY DISRUPT NEUROLOGICAL SYSTEM IN THIS CASE. THE NATIONAL FRAGILE X FOUNDATION IS ANOTHER GROUP OF PEOPLE WHO PARTNERED WITH NIH AND CDC AND FAMILIES TO PROMOTE WORK IN FRAGILE X SO THE GOAL IS COMMUNITY AWARENESS, CARE AND SUPPORT FOR FAMILIES WITH FRAGILE X AWARENESS TO HELP PROFESSIONALS AND OTHERS ABOUT FRAGILE X SYNDROME AND ASSOCIATED DISORDERS AND FINALLY RESEARCH, HOW CAN THEY FACILITATE RESEARCH. ONE IMPORTANT THING THEY HAVE DONE IS ESTABLISHED A FRAGILE X CLINICAL RESEARCH CONSORTIUM SO THAT'S 29 SPECIALTY CLINICS APPROVED FOR CARE WITH FRAGILE X SYNDROME. WITH THAT GROUP AND WITH THE STRONG SUPPORT OF CDC MONETARILY AND INTEL LOOK ACTUALLY CREATED THE FORWARD DATABASE, LONGITUDINAL STUDY, NATURAL HISTORY STUDY OF THOSE WITH FRAGILE X. YOU CAN SEE HERE JUST WHERE WE ARE AT THIS POINT BASELINE E VALUATIONS ON ABOUT 850 INDIVIDUALS, NOW STARTING TO GET INVOLVED IN FIRST AND SUBSEQUENT FOLLOW-UPS TO MAKE THIS A LONGITUDINAL STUDY. TAKES TIME TO GET THESE RESOURCES ESTABLISHED, THERE'S NOW PUBLICATION COMING OUT BASE ON THIS. LASTLY, WHAT THE FOUNDATION IS DOING, BUT AGAIN IN PARTNERSHIP WITH UC DAVIS, BUILDING A BIOBANK AND THEY THINK WHOLE IDEA IS TO BUILD TYPES OF RESOURCES AND PULL TOGETHER A BIOMARKER RESEARCH PROJECT TO FACILITATE RESEARCH SO GO THERE AND GET SAMPLES TO MOVE RESEARCH AHEAD. THIS IS BECOMING AN INTERNATIONAL EFFORT WHICH IS EXCITING. SPECIFICALLY AT THIS POINT BRINGING AWARENESS OF FRAGILE X TO OTHER COUNTRIES. SO WE HAVE COME A LONG WAY. AGAIN, WE HAVE VERY WELL DEFINED THE MECHANISM RELATED TO THESE TWO DIFFERENT CONDITIONS, DOWN SYNDROME AND FRAGILE X THAT IS THE FIRST STEP TO DIAGNOSE THESE CONDITIONS. WHAT IT IMPLIES IS THESE INDIVIDUALS HAVE DIFFERENT GENETIC BACKGROUND WHICH OTHER MODIFYING GENES AND ENVIRONMENTAL FACTORS MAY RESPOND DIFFERENTLY OR NOT. BUT IMPORTANT TO IDENTIFY AND UNDERSTAND THE CLINICAL VARIATION. SO AS WITH ALL OF US, THESE FACTORS NEED TO BE DEFINED IN ORDER TO BRING PRECISION MEDICINE TO THIS GROUP IN A MEANINGFUL WAY. IT TAKES EVERYBODY. AND AS MELISSA SAID NOT ONLY DOES IT TAKE EVERYBODY BUT EVERYTHING YOU LEARN ABOUT THESE INDIVIDUALS WILL APPLY TO ALL OF US IN TERMS OF DIFFERENT FACTORS THAT AFFECT THE PRECISION MEDICINE. SO THANK YOU. [APPLAUSE] >> THANK YOU VERY MUCH, DR. SHERMAN, I THINK WE CAN TAKE ONE QUESTION. SO WE HAVE THE BREAK COMING. WHY DON'T WE MOVE AHEAD TO OUR SEGMENT THAT I MENTION WE RECENTLY RENAMED THE VOICE OF THE PARTICIPANT. WE REALLY WANTEDDED TO FOCUS ON PEOPLE WHO WERE AFFECTED BY THE CONDITIONS WE STUDY AND WHO PARTICIPATEDDED IN RESEARCH STUDIES THAT WE FUND. YOU HEARD A LOT ABOUT NOTHING ABOUT OUT WITHOUT US. SO WE WOULD LIKE TO WELCOME MR. DAVID EGAN AND HIS MOTHER, DR. KATHLEEN EGAN. DAVID HAS BEEN LIVING HIS DREAM, STARTING AS A YOUNG SWIMMER WHO PARTICIPATED IN THE SPECIAL OLYMPICS. I HOPE EVERYBODY REALIZES THAT THERE ARE THREADS THAT ARE BEING WOVEN THROUGHOUT THIS WHOLE MORNING. AND THEN LATER AS AN ADVOCATE AND SPOKESPERSON FOR PEOPLE WITH INTELLECTUAL DISABILITIES. DAVID HAS SPOKEN AT INTERNATIONAL CONFERENCES, TESTIFIED AT U.S. SENATE HEARING AND ADDRESSED GLOBAL AUDIENCE AT UNITED NATIONS. DAVID'S DETERMINATION TO CHANGE ATTITUDES TOWARDS PEOPLE WITH INTELLECTUAL DISABILITIES HAS INSPIRED OTHERS TO LIVE THEIR DREAMS. PLEASE HELP ME TO WELCOME BOTH DAVID AND KATHLEEN EGAN. THANK YOU SO MUCH FOR COMING. [APPLAUSE] >> I'M GOING TO SPEAK FIRST BECAUSE IT'S HARD TO SPEAK AFTER DAVID. THANK YOU, DR. BIANCHI FOR INVITING US TO SPEAK TODAY AT YOUR ADVISORY COUNCIL MEETING. WE'RE HONORED TO BE AMONG YOU, ALL OF YOU, WHO STRIVE FOR UNDERSTANDING HUMAN CONDITIONS AND IMPROVING THE LIVES OF SO MANY SO WE'RE THANKFUL. ALSO I WANT THE TAKE THE OPPORTUNITY TO THANK DR. PARISI AND DR. HOE FOR INVITING US AND HELPING US WITH THIS PRESENTATION. SO I'M GOING TO TALK MORE ABOUT AS A MOTHER OF DAVID. OUR JOURNEY AT THE VERY BEGINNING. MY NAME IS KATHLEEN EGAN. I'M DAVID'S MOTHER. AND HE'S THE OLDEST OF FOUR KIDS. HE IS THE ONE I'M MOST PROUD OF HOWEVER ALL MY KIDS A ARE AMAZING BUT DAVID IS THE MOST FAMOUS ONE. HE'S WELL KNOWN, HE'S BEEN FEATURED LATELY IN BOOK ABOUT LEADERSHIP AND INSTIGATORS FIRE STARTERS AND HE'S IN BLOGS VIDEOS, YOU CAN GOOGLE HIM. MY HUSBAND AND I, THESE ARE HIS SIBLINGS. MY HUSBAND AND I WERE GRADUATE STUDENTS AT UNIVERSITY OF WISCONSIN WHEN DAVID WAS BORN ON SEPTEMBER 17th, 1977. I WAS 33 YEARS OLD. AND IT WAS A SURPRISE. WE DIDN'T EXPECT IT. WE WERE CRUSHED, I WAS IN DENIAL AND WE DIDN'T HAVE MUCH HELP AT THE TIME -- IT TOOK US SOME TIME. DAVID WAS SIX POUNDS 11 WHICH I THINK IS AVERAGE. AND TESTIFIES TO ME HE WAS BEAUTIFUL AND WONDERFUL AND I DIDN'T BELIEVE WHAT THEY WERE TELLING ME. SO WE TOOK DAVID HOME, HE WAS FIVE POUNDS BY THE TIME HE WAS JAUNDICED AND HE HAD HEART DEFECT PSD CONGENITAL DEFECT. WE WERE DETERMINED TO DO EVERYTHING WE COULD TO GIVE HIM THE BEST LIFE WE COULD. OURPEDIA US FROM WAS WONDERFUL. WE HAD GOOD CARDIOLOGISTS AND THEY ADVISED AGAINST ANY SURGERY. SO HE DIDN'T HAVE SURGERY. DAVID SLEPT LONG HOURS. HE WOULDN'T WAKE UP MANY TIMES WE HAD TO WAKE HIM UP TO FEED HIM. I DECIDED TO NURSE, I NURSED THREE MONTHS TRYING TO GIVE HIM AS MUCH AS YOU COULD. THEN WE HAD TO ARD FORMULA AND DIGITALIS TO GIVE HIM THE STRENGTH TO THRIVE. HAVING DAVID AT THE UNIVERSITY WAS A WONDERFUL THING, IT WAS REALLY A BLESSING TO BE AT THE UNIVERSITY OF WISCONSIN IN MADISON. WE WERE SURROUNDED BY WONDERFUL DOCTORS, RESEARCHERS, MEDICAL PEOPLE, WE WERE BOTH GRADUATE STUDENTS SO IT MADE IT EASY TO ACCESS PEOPLE WITH EXPERTISE. THAT MADE A BIG DIFFERENCE. DAVID HAD FOUR BABYSITTERS, CARDIOLOGISTS, ENGINEERS, PHYSICISTS, MUSICIANS, EDUCATORS. SO HE WAS SURROUNDED WONDERFULLY AFTER THREE MONTHS ADVISERS TOOK ME TO GENETICISTS DR. O PITTS, MAYBE YOU KNOW ABOUT DR. O PITTS. HIS HAND WERE LONG HANDS, DAVID WAS LITTLE IN ONE HAND. AND HE GAVE US EXTENSIVE INFORMATION ABOUT THE 44 SYMPTOMS OF DOWN SYNDROME. HE WAS TYPICAL TRISOMY 21, IT WAS TOO MUCH FOR ME. MY HUSBAND JOHN WHO IS HERE ENJOYED IT MORE THAN I DID. IT WAS TOUGH. SOME SUGGESTED INSTITUTION, BUT WE WERE DETERMINED WE WERE GOING TO TAKE HIM HOME AND DO WHATEVER WE COULD TO MAKE HIS LIFE BEST. SO HE WAS BECOME OBJECT OF OUR STUDY. WE WERE RESEARCHERS SO WE WATCHED EVERY MOVEMENT HE WOULD DO. WE WANTED TO MAKE SURE HE WOULD THRIVE AND BE HAPPY. HE WAS AN INTERESTING CHARACTER. DAVID EARLY, EARLY ON SHOWED LEADERSHIP CHARACTERISTICS. HE WAS INTERACTIVE, SOCIAL AND WE HAD POTLUCK PARTIES ON CAMPUS WITH GRADUATE STUDENTS, EVERYBODY WANTED TO HOLD DAVID. HE WAS THE STAR. HE ENJOYED MUSIC. WE HAD A GROUP OF MEXICAN FRIENDS, WE MEET WITH THEM ON REGULAR BASIS. AND HE'S THEIR FRIENDS. HE MADE FRIENDS AND EVERYBODY LOVED HIM. SO SOON BECAUSE OF OUR INVOLVEMENT IN THE GRADUATE SCHOOL WE MET DR. -- AND THEY FOLLOWED DAVID ON A MONTHLY BASIS, THEY COME TO OUR HOME AND FILM HIM. WE HAVE MOVIES OF DAVID AND EVERY STEP IN MISHIS MOVEMENT, WHEN HE DID BUTTERFLY, ERR PLAIN, GOING BACKWARDS, FORWARD, THOSE SESSIONS WERE GOOD FOR ME. AS FIRST TIME MOM IT GAVE ABILITY TO OBSERVE AND LEARN LITTLE SUCCESSES AND E BEEN BEGAN TO LEARN TO APPRECIATE WHAT HE COULD DO OPPOSED TO WHAT HE COULDN'T DO, AT THING BEING I LOOKED TO WHAT CAN I FIX IN DATA AND QUICKLY THROUGH THOSE OBSERVATIONS I LEARNED TO LEARN WHAT HE CAN DO. WHAT I ALSO LEARN WHICH CAME GOOD FOR ME FOR HAVING OTHER THREE CHILDREN IS TO BE MORE TOLERANT AND UNDERSTAND THAT NO TWO KIDS DEVELOP ALIKE. THEY'RE VERY DIFFERENT, EACH HAS OWN PERSONALITIES AND THEIR OWN STRENGTHS. DAVID DEVELOPED THROUGH THE CURVE. HE DID EVERYTHING A NORMAL CHILD WOULD DO. HOWEVER, IT WAS MUCH SLOWER. IT WAS SLOW, IT WAS SOMETIMES PAINFUL, IT WAS HARD ON ME. SO AS I WAS WE DID -- RECOMMENDED TO US WE SEND DAVID TO KIDDY CAMP, IT WAS A SPECIAL EDUCATION PRE-SCHOOL. AND THEY THOUGHT THEY COULD GIVE HIM MORE PHYSICAL THERAPY,, AND OCCUPATIONAL THERAPY, SO FORTH. I WOULD GO DROP DROP HUM OFF AND I WOULD PEAK AND TEACHERS WERE LOVING AND I WOULD COME HOME AN DISCUSS WITH JOHN AND SAY I'M CONCERNED Is NOTS GOING THE WAY I THINK IT SHOULD BE. HE'S NOT DOING WHAT I THINK HE CAN DO. SO WE DECIDED DAVID NEEDED TO BE AROUND ALL KIDS WITH AND WITHOUT DISABILITIES. SO THROUGH THE GRADUATE SCHOOL, I HAD FRIENDS SO I CREATESSED A PLAY GROUP IN MY HOME. KIDS WITH FRIENDS WOULD COME O A WEEKLY BASIS AND HE WOULD IMITATE AND DO WHAT HE DID. IT WAS HARD ON ME BECAUSE I COULD SEE DAVID WAS THE SLOWEST ONE, HE WASN'T DOING WHAT THE ORCHIDS COULD DO. BUT I THINK I LEARNED ACCEPTANCE, I LEARNED PATIENCE. JUST GIVE HIM SOME TIME. WERE LUCKY, WISEMAN CENTER AT UNIVERSITY OF WISCONSIN OPENED THIS WISEMAN EARLY CHILDHOOD PROGRAM. DAVE WAS THE FIRST KID WITH ANOTHER KID WITH AUTISM TO BE ENROLLED IN THE PROGRAM. A SPECIAL ED TEACHER WOULD COME IN ONCE A WEEKS, TWO TIMES WEEK AND HELP IN THE CLASSROOM. DAVID MADE FRIENDS, WE SAW AMAZING PROGRESS, WE WERE TRULY INCLUSION WORKS. IT REALLY DID WORK IN A FABULOUS WAY. DAVID SPOKE, HE WAS ENGAGED. HIS MOTIVATION, HE'S A COMPETITIVE KID AND HE WANTED TO DO WHAT THE ORCHIDS. SO HE WOULD FORCE HIMSELF TO CLIMB ON THINGS AND IMPROVE. THAT PROGRAM WHICH STARTED WITH 12 KIDS HAS NOW 100 KIDS WITH TWO-THIRDS OF THEM WITH DISABILITY OR LEARNING DEVELOPMENT. I BELIEVE EARLY INTERVENTION IS CRUCIAL AND KEY TO DAVID'S SUCCESS. HE WOULD PLATEAU AT TIMES AND JOHN AND I WOULD BECOME NERVOUS, WILL HE STAY THERE, THEN HE WOULD SURPRISE US AND HE HAS KEPT SURPRISING US FOR THE YEARS APPROXIMATE YEARS TO BE. SO AFTER COMPLETING MY Ph.D. IN 1980, I FOUND A JOB AT THE UNIVERSITY, I WAS PROGRAM EVALUATOR FOR NURSE PRACTITIONERS PEDIATRICS AND GERIATRICIAN TO HELP DESIGN PROJECTS. IT WAS A WONDERFUL EXPERIENCE BECAUSE I WAS VERY CLOSE WITH THE MEDICAL PROFESSION. I COULD TALK TO THEM, I COULD LEARN MORE AND HELP THEM TOO. DAVID BECAME THEIR OBJECTED OF STUDY, HE WAS OBSERVED, ABLE LISTEN TO HIS HEART, THEY WOULD USE HIM FOR NEW STUDENTS, NURSES, AND HE WAS FEATURED IN A TEXTBOOK, OBSTETRIC TEXTBOOKS THE TEXTBOOK EARLIER DIDN'T HAVE FEATURE CONSIST OF PICTURES WITH DOWN SYNDROME AND DIDN'T HAVE PICTURE OF FAMILY. IT HAS A NEW CHAPTER IN THE BOOK ABOUT ADAPTIVE METHODS FOR EXTENDED FAMILY. HOW TO INCLUDE THE FAMILY IN THE NURSING AND NURTURING OF KIDS WITH DISABILITIES SO THAT WAS WONDERFUL. FAMILY INCLUSION IS IMPORTANT SO WE DECIDED TO HAVE MORE CHILDREN. WE HAVE THREE OTHERS. THERESA IS TWO YEARS YOUNGER THAN DAVID, THREE YEARS YOUNGER AND SHE WAS INSTRUMENTAL, SHE ADVANCE VERY QUICKLY IN LANGUAGE. SLEEVES SPEAKING AT 15 MONTHS SO SHE TRULY HELPED DAVID IMPROVE IN HIS LANGUAGE SKILLS AND GROSS MOTHER SKILLS. SHE WAS REALLY CRITICAL IN THAT. THEN WE HAD NINE YEARS LATER MIRANDA AND MARK, MARK IS 12 YEARS YOUNGER THAN DAVID. SO DAVID BECAME THE BIG BROTHER. HE FELT HE WAS NUMBER ONE AND HE REALLY HELPED HIS BROTHERS AND CHANGED OUR LIVES. ALL IN THIS BROTHERS AND SISTERS WERE INVOLVED IN SPECIAL OLYMPICS. ALL FANS AND VOLUNTEERS. JOHN IS A COACH. HIS BROTHER PLAYS IN UNIFIED SPORTS. SO IT HAS CHANGED OUR LIVES. FOR THE BETTER. I WOULD ALSO SAY SMALL ANECDOTE. IN THE PAST I WOULD TAKE DAVID PLACES NOW HE TAKES ME PLACES. I WOULDN'T BE HERE WITH OUTNOT FOR DAVID AND I FEEL VERY HONORED BY HIM. WHILE THERE WERE CHALLENGES, YOU KNOW, MEDICAL, HEALTH, COGNITIVE SOCIAL AT TIMES. I WOULD SAY THE EXPERIENCE HAS BEEN FANTASTIC. THROUGH OUR JOURNEY DAVID TAUGHT ME TO BE -- TO HAVE GRATITUDE, PATIENCE, ACCEPTANCE OF DIFFERENCES. AT THE SAME TIME GAVE US LOTS OF REASONS TO CHEER. TO LAUGH. WE LAUGH A LOT AROUND DAVID, EXPAND CIRCLE OF FRIENDS, WHO CHANGED OUR PERSPECTIVES AND ALL FOR THE BETTER. ALL IN ALL TRANSITION FROM FROM CHILD TO ADULTHOOD HAS BEEN SMOOTH. HE HAS A JOB FULL TIME, HE HAS A GOOD LIFE. WHAT COULD I ASK FOR MORE? AS DAVID TURNED 40 I BEGIN TO WORRY A LITTLE AND I'M WORRIED ABOUT THE AGING PROCESS. WE DON'T HAVE A GOOD UNDERSTANDING OF WHY SOME HAVE ALZHEIMER'S AND WHY SOME DO NOT SO WE ARE GRATEFUL AND HOPE THAT THE NICHD AND NIH FOR AGING RESEARCH PARTNERSHIP INITIATED BY DR. PARISI WILL CONTINUE. AND WILL INCREASE. WE NEED ANSWERS, WE NEED GUIDELINES. WE NEED TO KNOW HOW TO NAVIGATE NEXT PHASE OF HIS LIFE. I HOPE WE CAN EXPLORE BRAIN STRUCTURES, HOW THEY WORK HOW TO GROW NEURONS, THROUGH THE LIFE SPAN. WHAT ARE THE PHYSIOLOGICAL PSYCHOLOGICAL SOCIAL FACTORS THAT WILL HELP OUR KIDS TO REACH FULL POTENTIAL. IN CLOSING MY PRESENTATION, I WANT TO STRESS WE ARE A FAMILY THAT SUPPORTS RESEARCH. THIS IS DAVID WHEN HE WAS IN PRE-SCHOOL AT THE WISEMAN CENTER. SO WHILE DESIRED EXPERIMENTS WELL THOUGHT CLINICAL TRIALS UNVEIL NEW INFORMATION THAT WILL IMPROVE THE LIVES OF MANY CHILDREN AND THOSE WITH DOWN SYNDROME WE HOPE MANY PEOPLE, FAMILIES WILL ENENROLL IN THE DS CONNECT. WE NEED MORE BECAUSE I KNOW THAT IN THE RESEARCH YOU NEED DATA. WITHOUT DATA YOU CANNOT DO WELL DESIGNED GENERALIZED CONCLUSIONS. I'M VERY GLAD ABOUT THAT. WHILE ALL CHILDREN NEED ATTENTION THOSE WITH INTELLECTUAL AND DEVELOPMENTAL DISABILITIES NEED A LITTLE MORE. I QUESTIONING AND ASK YOU TO CONTINUE THE GOOD WORK YOU DO. AND WE THINK IT WOULD BE A GOOD THING FOR EVERYBODY. WITHOUT FURTHER ADIEU, MY HONOR TO PRESENT TO YOU DAVID EGAN. [APPLAUSE] >> GOOD MORNING, EVERYONE. NORMALLY I SPEAK TO SPECIAL OLYMPICS I LIKE TO GET EVEN UP, HOW IS EVERYONE DOING TODAY? OKAY. WE CAN DO BETTER. FIST I WANT TO START BY THANKING MY FAMILY WHO IS HERE, MY MOM, KATHLEEN EGAN, THANK YOU VERY MUCH FOR INTRODUCING ME. MY DAD, JOHN EGAN WHO IS ALSO HERE TOO AND MY MENTOR, DAVID THOMASSON. MY NAME IS DAVID EGAN, I'M E HONORED TO SPEAK AT YOUR COUNCIL ADVISORY MEETING THIS IS MY SECOND TIME AT NIH. IN 2007 I ATTENDED THE EVENT WHEN THE INSTITUTE WAS RENAMED IN ON NOR OF MS. EUNICE KENNEDY SHRIVER. THAT WAS A HISTORIC DAY FOCUS ON HER VISION, DEDICATION AND CONTRIBUTIONS. OUR ABILITIES RATHER THAN DISABILITIES. I'M PRIVILEGEDDED TO HAVE KNOWN MS. SHRIVER WHO HAS INSPIRED ME AND MANY OTHERS TO PURSUE OUR DREAMS AND SHARED OUR HUMAN RIGHTS. SHE BELIEVED IN US. SHE HAD A JEEPIOUS IDEA USING SPORES AS A CATALYST FOR CHANGING THE WAY PEOPLE WHO PERCEIVE US. I WISH SHE WAS HERE TODAY. TO SEE MY PRESENTATION AND I'M GLAD HER SON DR. TIM SHRIVER IS ON YOUR ADVISORY COUNCIL. I WAS BORN WITH AN EXTRA CHROMOSOME. I'M HERE TODAY TO SHARE WITH YOU A LITTLE BIT ABOUT MY STORY AND INVOLVEMENT WITH RESEARCH. THANK YOU FOR THE ONGOING STUDIES AND I URGE YOU TO CONTINUE AND EXTEND PROJECTS ON DOWN SYNDROME. IT IS AN INVESTMENT THAT PAY OFF AND YOU WILL NOT REGRET IT. I AM LIVING PROOF IT WORKS. I DON'T THINK THAT WHEN I WAS BORN MY PARENTS IMAGINE ME AS ADVOCATE FOR PEOPLE WITH INTELLECTUAL KISS ABILITIES. DISABILITIES. I DON'T THINK THEY EXPECTED ME TO BE PUBLIC SPEAKER TO TESTIFY ABOUT THE COMPETITIVE EMPLOYMENT, AT THE SENATE IN WASHINGTON D.C., SPEAK FOR WORLD DOWN SYNDROME DAY AT THE UNITED NATIONS, TO SERVE AS A SHRIVER INTERNATIONAL MESSENGER. CHOSEN ONE OF ONLY 12 IN THE WORLD TO REPRESENT OUR MOVEMENT AND COMPETE IN A VARIETY OF SPECIAL OLYMPICS SPORTS. I ALSO HAVE PRIVILEGE TO BE SELECTED AS FIRST EVER JOSEPH P. KENNEDY JR. PUBLIC POLICY FELLOW WITH INTELLECTUAL DISABILITY. IN 2015 I SERVED FOR ONE YEAR ON CAPITOL HILL WITH THE WAYS AN MEANS SOCIAL SECURITY SUBCOMMITTEE AND THEN WITH THE NATIONAL DOWN SYNDROME SOCIETY. THIS THOSE ARE TRUE HISTORIC MILESTONES. MY GOALS AND LEADERSHIP HAVE ALWAYS FOCUSED ON BREAKING DOWN BARRIERS. THAT FELLOWSHIP OFFERED ME OPPORTUNITIES TO MEET WITH SEVERAL CONGRESSIONAL MEMBERS TO LEARN ABOUT PUBLIC POLICY. IN FACT THERE'S ALMOST A DIRECT RELATIONSHIP BETWEEN QUALITY OF LIFE AND PEOPLE HAVE IN ACTIONS OR INACTIONS THAT TAKE PLACE IN PUBLIC POLICY. ALSO RESEARCH STUDIES ON INTELLECTUAL DISABILITIES ARE CRITICAL TO OUR WELL BEING UNTIL RECENTLY WE WERE OVERLOOKED AND UNDERAPPRECIATED BY SOCIETY AT LARGE. I WAS BORN IN 1977 AND I HAVE BEEN FIRST GENERATION OF DOWN SYNDROME INDIVIDUAL TO BREAK FREE FROM THE INSTITUTIONS THAT PREVIOUS THROUGH PLAGUED OUR POTENTIAL. I HOPE NEXT GENERATION OF INDIVIDUALS WITH INTELLECTUAL DISABILITIES AND DEVELOPMENTAL DISABILITIES CAN LIVE LONG AND PROSPER. HE TEACHES US THE THINGS THAT MAKE US DIFFERENT ARE THE SAME THINGS THAT MAKE US AWESOME. I AM A STAR TREK FAN AND LOVE SCIENCE FICTION. IF WE DREAM WE CAN IMAGINE A WORLD THAT GREETS PEOPLE WHO ARE DIFFERENT WITH RESPECT AND INCLUSIVE ACTIONS WHO ALL CONTRIBUTE I'M PROUD TO SAY I HAVE EXPERIENCE IN INCLUSIVE LIFE AND COMPETITIVE EMPLOYMENT, I STARTED AS AN INTERN WHEN I I WAS HIRED BY BOOZE ALANRS AGO. HAMILTON, INTERNATIONAL CONSULTING FIRM AND THEN BY CPRE A GLOBAL REAL ESTATE COMPANY AS CLERK IN THE DISTRIBUTION CENTER. I WAS FULLY INCLUDED ON THE JOB. I HAD BENEFITS AND ANNUAL ASSESS P LIKE EVERYONE ELSE. ONE OF THEM AND NOT ONE AMONG THEM. THIS PAST SEPTEMBER I GOT A NEW JOB WITH SOURCE AMERICA AS COMMUNITY RELATIONS SPECIALIST IN THE GOVERNMENT AFFAIRS DEPARTMENT. SOURCE AMERICA IS THE BIGGEST NATIONAL NON-PROFIT ORGANIZATION THAT PROVIDES EMPLOYMENT OPPORTUNITIES AND CHOICES FOR PEOPLE WITH DISABLES. I'M SHARING MY EMPLOYMENT CAREER BECAUSE I WANT TO STRESS PEOPLE WITH INTELLECTUAL DISABILITIES ARE CAPE CAPABLE INDIVIDUALS. IT'S ABOUT BEING VALUED ABLE AND READY TO WORK. AS I WROTE IN MY PROJECT DURING MY FELLOWSHIP AT NDSS AS PART OF THE HASH TAG EMPLOYMENT CAMPAIGN. MY SUCCESS AND MY ABILITY TO MAKE MY DREAMS COME TRUE AND HAVE A LIFE LIKE YOURS WAS POSSIBLE THANKS TO SUPPORT OF FAMILY AND PEOPLE WHO BELIEVED IN ME. THAT TOOK THE TIME TO TEACH ME AND LEND ME HELPING HAND. I WAS MOTIVATED TO RISE TO THECATION. WHEN I WAS YOUNG, I RECALL GOING TO THE HOSPITAL TO HAVE MY TONSILS TAKEN OUT. I ASKED MY MOTHER IF THEY WOULD BE REMOVING THE DOWN SYNDROME THING TOO. SHE SAID IT IS SOMETHING THAT STAYS WITH YOU ALL YOUR LIFE, IT DOESN'T STOP YOU FROM HAVING DEEPS AND BEING SUCCESSFUL. SHE WAS RIGHT. IT'S NOT AN OBSTACLE TO SUCCESS. IN FACT DOWN'S SYNDROME DOES NOT DEFINE ME AS A PERSON. AS I TURN 40 THIS PAST SEPTEMBER, I'M NOT SURE WHAT THE FUTURE WILL LOOK LIKE, SHOULD I WORRY? WHILE WE MADE SOME PROGRESS IN THE ACCEPTANCE OF PEOPLE WITH INTELLECTUAL DISABILITIES, OUR QUALITY OF LIFE HAS GREATLY IMPROVED, WE STILL HAVE NO ANSWERS ON PREVENTING OR CURING HEART DEFECTS. ALZHEIMER'S APPROXIMATE OTHER DISEASES. THERE ARE MORE ADULTS WITH DOWN SYNDROME LIVING LONGER AND OUR AGING POPULATION IS AT HIGH RISK OF BEING AFFECTED BY ALZHEIMER'S IN FACT OUR QUALITY OF LIFE AND THAT OF MANY OTHERS WITH AND WITHOUT DOWN SYNDROME COULD BE IMPROVED WITH FURTHER SCIENTIFIC RESEARCH FROM CRADLE TO GRAVE. FROM PRENATAL TESTING SHOULDN'T BE ABOUT ELIMINATING THE FETUS BUT RATHER UNDERSTANDING US, GIVING UNBIASED INFORMATION TO PARENTS ALLOWING RESEARCHERS EXPLORE CURES HELPING OVERCOME LIMITATIONS SLOW DOWN DEVELOPMENT AND SHOW INCLUSION. MY INVOLVEMENT IN VERGE STARTED RESEARCH STARTED EARLY AT THE SENT UNIVERSITY WISCONSIN MADISON. WE STAYEDED IN TOUCH WITH FRIENDS AT THE UNIVERSITY AND MY FAMILY AND I WENT BACK TO VISIT 25 YEARS LATER AND ALSO 2013. WHEN I SPOKE AT MEMORIAL EVENT FOR MY TEACHER AND MET STUDENTS AND PARENTS. DURING THAT VISIT, MY DAD AND I VOLUNTEERED OURSELVES AND DONATE SKIN BIOPSIES FOR THE LATEST INDUCE PLURIPOTENT STEM CELL RESEARCH STUDIES. WE ALSO GAVE BLOOD SAMPLES. AT THE SAME TIME I AND TWO OTHERS WITH DISABILITY GAVE A TALK TO THE MEDICAL RESEARCH COMMUNITY, CALLED REFLECTION ON INCLUSION. OUR ABILITY TO WORK AND CONTRIBUTE AND LIVE IN THE COMMUNITY. THERE WERE -- THEY WERE IMPRESSED. I'M ALSO A SUPPORTER OF DS CONNECT REGISTRY, IT'S A POWERFUL RESOURCE. I WAS PRIVILEGED TO BE FILMED AT THE REQUEST OF DR. PARISI WHERE VIDEO ENCOURAGING FAMILIES, TO REGISTER AND SHARE THEIR INFORMATION. THANKS TO HER AND HER TEAM THE DATABASE AND THE RESEARCH THAT WERE FOLLOW HELP US IMPROVE QUALITY O OUR LIVES, PLEASE CHECK OUT AND WATCH THE VIDEO. I'M ALSO HONORED TO HAVE BEEN INTERVIEWED AND FEATURED ON THE NIH SPOTLIGHT, PLEASE DO CHECK OUT THAT LINK TOO. I'M VERY FORTUNATE TO HAVE A GOOD LIFE BUT THAT IS NOT THE CASE FOR MANY OTHERS WHO HAVE NOT HAD THE SUPPORT OF FAMILY, COMMUNITY SERVICES, AND ENVIRONMENT TO HELP US THRIVE. LEARN AND REACH FULL POTENTIAL. I THINK RESEARCH IS NEEDED AND THE EXTRA CHROMOSOME MAY UNLOCK DISCOVERIES MAY BENEFIT NOT ONLY DOWN'S SYNDROME BUT THE LARGER POPULATION. ANYTHING THAT CAN GIVE US AN EDGE TO LEAD FULFILLING LIVES IS WORTH PURSUING. THAT'S WHY I'M HERE TODAY TO URGE YOU CONTINUE TO SUPPORT DOWN SYNDROME RESEARCH, I HOPE MEDICAL AND RESEARCH COMMUNITY WILL FIND STUDYING DOWN SYNDROME TO BE EXCITING AND INTERESTING. I HOPE THEY FIND OUT THE EXTRA CHROMOSOME MAY UNLOCK DISCOVERIES HOW THE BRAIN WORKS AND SOCIAL SKILLS. MAYBE RESEARCH ON DOWN SYNDROME MAKE EASIER TO UNDERSTAND DISEASES THAT AFFECT US ALL. I'M ALSO AVAILABLE AND WILLING TO HELP SPREAD WORD AT UNIVERSITIES, HOSPITALS, RESEARCH CENTERS, IN THE U.S. AND ACROSS THE GLOBE. TO INSPIRE INDIVIDUALS TO HAVE INNOVATIVE PROPOSALS THAT MERIT YOUR ATTENTION AND TAXPAYER MONEY SHOW THEM HOW WE ARE MORE ALIKE THAN DIFFERENT. THANK YOU. THANK YOU ALL. [APPLAUSE] >> THANK YOU SO MUCH, DAVID, FOR SHARING YOUR STORY WITH US. NOW WE OBVIOUSLY UNDERSTAND WHY œYOUR MOTHER WANTED TO GO FIRST. AND I DO WANT TO APOLOGIZE TO DAVID'S DAD, YOU WERE SITTING RIGHT NEXT TO EACH OTHER, I SAID YOU HAVE TO BE FATHER AND SON BUT IT WASN'T IN THE NOTES THAT YOU ARE GOING TO BE HERE SO I APOLOGIZE FOR NOT INTRODUCING YOU AT THE BEGINNING. BUT WE'RE THRILLED WITH YOU TO BE HERE AS WELL. SINCE WE'RE OVER WE'LL ONLY BE ABLE THE TAKE A FIVE MINUTE BREAK. DAVID, THERE'S NO SUCH THING. THAT'S RIGHT. THE TOILETS ARE DOWNSTAIRS. WE HAVE TO GO DOWNSTAIRS. TAKE A TEN MINUTE BREAK WELCOME BACK, EVERYONE. OUR NEXT PRESENTER WHO IS TEED UP READY TO GO IS DR. DAVID MURRAY, NIH ASSOCIATE DIRECTOR FOR PREVENTION AND DIRECTOR OF OFFICE OF DISEASE PREVENTION OR ORDP REFERRED TO HERE. DR. MURRAY WILL PROVIDE US AN UPDATE ON ODP AT THE NIH. PLEASE WELCOME DR. MARY. >> THANK YOU. I'M GOING TO DO MY BEST TO CATCH UP A LITTLE BIT. WE'RE TEN MINUTES BEHIND SCHEDULE BUT I HAVE SOME THINGS THE TALK TO YOU ABOUT AND I VERY MUCH WANT TO HEAR YOUR THOUGHTS ON HOW OFFICE OF DISEASE PREVENTION AT NIH CAN HELP NICHD ADVANCE PREVENTION RESEARCH. SO A LITTLE BIT ABOUT THE OFFICE. THE OFFICE OF DISEASE PREVENTION IS OFFICE OF DIRECTOR. SO NOT PART OF THE ICs, WE'RE OD AS WE CALL IT HERE DIVISION OF PROGRAM COORDINATION PLANNING AND STRATEGIC INITIATIVES. AND WE ALONG WITH OFFICE OF AGE RESEARCH, OFFICE OF RESEARCH WOMEN'S HEALTH, OFFICE OF BEHAVIORAL SOCIAL SCIENCES ARE SET OF FOUR PROGRAMMATIC OFFICES IN DPKPSI PART OF DOD. OUR MISSION TO IMPROVE PUBLIC HEALTH INCREASING THE SCOPE QUALITY DISSEMINATION AND IMPACT OF PREVENTION RESEARCH SUPPORTED BY NIH. WE PROVIDE LEADERSHIP BUT CAN'T ACCOMPLISH ANYTHING WITHOUT WORKING CHOSELY WITH THE INSTITUTES AND CENTERS AND OTHER OFFICES AROUND THIS CAMPUS BECAUSE WE ARE A SMALL GROUP WITH SUCH A SMALL BUDGET YOU CAN'T IMAGINE AND THE RESOURCES BELONG TO THE INSTITUTES AND CENTERS SO COLLABORATION IS KEY. ONE SLIDE ON CURRENT ACTIVITIES AND THEN PRIORITIES LOOKING FORWARD. ONE THING WE DO IS MANAGE TOBACCO REGULATORY SCIENCE PROGRAM FOR NIH. A $100 MILLION FUNDING PROGRAM USING DOLLARS THAT COME TO US FROM FDA, TO SUPPORT TOBACCO REGULATORY SCIENCE. NICHD HAS BEEN INVOLVED IN THAT EFFORT CERTAINLY WAS INVOLVED IN THE BEGINNING BUT HAS NOT TAKEN ON ANY GRANTS RECENTLY SO THAT'S AREA FOR ADDITIONAL COLLABORATION GOING FORWARD. WE ARE THE LIAISON OFFICE FOR A NUMBER OF OTHER GROUPS IN THE DEPARTMENT. I WILL TALK ABOUT WORK WITH U.S. PREVENTATIVE SERVICES TASK FORCE AND COMMUNITY PREVENTATIVE SERVICES TASK FORCE, ALSO LIAISON FOR HELPING PEOPLE. WE OFFER EVIDENCE BASED WORKSHOP SERIES CALLED PATHWAYS TO PREVENTION. WE OFFER TRAINING PROGRAMS, WE DO SOME CO-FUNDING NOT A GREAT DEAL BECAUSE BUDGET IS LIMITED WE HAVE A STAFF OF 30 PEOPLE. ONE PRIORITY WE HAVE BEEN PURSUING AND WHICH WE INTEND TO PURSUE IS TO MONITOR NIH INVESTMENTS AND PREVENTION RESEARCH AND PARTICULARLY RESULTS OF THAT RESEARCH. WE FOCUS ON FIGURING WHAT IT IS NIH IS SUPPORTING. WHEN I ARRIVED IN LATE 2012 I ASSUMEDED THAT MY STAFF WOULD BE ABLE TO TELL ME HOW MUCH IS NIH PUTTING INTO THIS PREVENTION RESEARCH AND THAT PREVENTION RESERVING, USING THIS DESIGN OR THAT METHOD. THE METHODS AVAILABLE TO US, HOW MUCH WE'RE DOING IN DIFFERENT AREAS ARE NOT VERY GOOD. SO WE DEVELOPED A TAXONOMY PREVENTION RESEARCH WITH AGO CATEGORIES, 135 TOPICS CODED THOUSANDS OF TYPE ONE RO1s TO KICK OFF OUR EFFORT DEVELOPING A BETTER SYSTEM FOR PORTFOLIO ANALYSIS. WE THEN COLLABORATEDD WITH OFFICE OF PORTFOLIO ANALYSIS IN THE OD TO DEVELOP MACHINE LEARNING TOOLS AUTOMATING THE PROCESS. WE CODED 15,000 RP U AWARD FROM FY 12 THROUGH 17 USING MACHINE LEARNING TOOLS TO GUIDE CHOOSE THE AWARDS. WE WILL START PUBLISHING OUT OF THAT WORK IN 2018. I NEED TO COME BACK TO IC DIRECTORS TO UPDATE IN THE REPORT AND HOPE TO DO THAT THE NEXT MONTH. GOING FORWARD WE WANT TO CONTINUE THIS WORK SO WE CAN BETTER CHARACTERIZE AND REPORT ON THE NIH RESEARCH PORTFOLIO ON TAXONOMY, WE WANT TO REGULARLY ASSESS THE PROGRESS AND RESULTS OF THE WORK AND PARTNER WITH OTHER INSTITUTES CENTERS AND OFFICES DISSEMINATING RESULTS OF THAT PORTFOLIO ANALYSIS EFFORT. SECOND PRIORITY TO IDENTIFY RESEARCH GAPS FOR EXPANDED INVESTMENT OR EFFORT BY THE NIH. ICs LOOK TO OUR OFFICE OR ADVICE ON WHAT THINGS TO DO IN PREVENTION AREA, BETTER PORTFOLIO ANALYSIS METHODS WILL HELP BUT IN ADDITION, REGULAR INTERACTION WITH KEY STAKEHOLDERS CAN BE IMPORTANT. WE TRY TO DO THAT. OVER THE LAST FIVE YEARS WE HAVE IMPROVED COORDINATION BETWEEN NIH AND PREVENTATIVE SERVICES TASK FORCE WE ATTEND MEETINGS, WE COMMENT ON ON TOPICS UNDER CONSIDERATION FOR REVIEW. WE WORK WITH ICs TO MAKE NOMINATIONS FOR MEMBERSHIP ON THE PANEL, AND COORDINATE REVIEW OF DRAFT EVIDENCE STATEMENTS AND RECOMMENDATIONS AND PUBLICITY FOR FINAL EVIDENCE REVIEWS AND STATEMENTS. WE DO SIMILAR THINGS WITH THE COMMUNITY PREVENTATIVE SERVICES TASK FORCE AND WE HAVE PARTNERD WITH THE OFFICE OF DISEASE PREVENTION AND HEALTH PROMOTION AT THE DEPARTMENT LEVEL TO SUPPORT HEALTHY PEOPLE. I MENTIONED OUR PATHWAYS TO PREVENTION WORKSHOPS EARLIER. GOING FORWARD WE'LL CONTINUE THESE ACTIVITIES TO WORK WITH ALL THESE STAKEHOLDERS. ONE OF THE ACTIVITIES WE'RE DOING USPSTF IS CONDUCT ANNUAL SURVEY OF INSTITUTES AN CENTERS OF THE WORK THEY'RE DOING RELEVANT TO INSUFFICIENT EVIDENCE STATEMENTS. WE'RE TRYING TO HELP THE ICs, DETERMINE WHETHER THERE ARE ACTIVITIES THEY COULD BE PURSUING TO ADDRESS THOSE EVIDENCE GAPS SO THE TASK FORCE CAN MOVE FROM INSUFFICIENT EVIDENCE STATEMENT TO LETTER GRADE. AND WE'LL CONTINUE TO DO THAT AS WE GO FORWARD. WE CERTAINLY WANT THE PROMOTE USE OF BEST AVAILABLE METHODS IN PREVENTION RESEARCH ACROSS NIH. I'M A METHOD DOLL GIST AT HEART, WORK JUST AS EPIDEMIOLOGIST FOR ACADEMIA BEFORE COMING HERE, MY EXPERIENCE AS REVIEWER FOR 33 YEARS ON REVIEW PANELS AT NIH, TOLD ME THAT REVIEWERS WEREN'T ALWAYS UP TO DATE ON THE BEST METHODS THE PROGRAM OFFICERS AND SROs WEREN'T ALWAYS UP TO DAY SO WE IS IT OUT TO DO SOME THINGS TO TRY TO ADDRESS THAT. WE CREATED AND POSTED ONLINE 7 PART COURSE ON PRAGMATIC AND GROUP RANDOMIZED TRIALS IN PUBLIC HEALTH AND MEDICINE OUT THERE FOR ANYONE INTERESTED IN VIEWING IT. WE HAVE RECENTLY ADDED LANGUAGE TO THE APPLICATION GUIDE FOR AWARDS THAT WOULD BE COMING IN ON AND AFTER JANUARY 25th AND REVIEW CRITERIA USED TO EVALUATE THE 'WARDS TO DRAW ATTENTION TO CERTAIN METHODOLOGICAL PROBLEMS THAT ARE COMMON PARTICULARLY IN CLINICAL TRIALS USED NO T JUST IN PREVENTION RESEARCH BUT GENERALLY ACROSS NIH. WE ARE TRYING TO PROVIDE RESOURCES TO EXTRAMURAL COMMUNITY, AND TO PROGRAM OFFICER AND REVIEW OFFICERS HERE AT NIH TO HELP UNDERSTAND WHAT THESE ISSUES ARE AND GIVE BETTER ADVICE TO INVESTIGATORS THAT ARE PUTTING PROPOSALS TOGETHER. WE HAVE DEVELOPED A PREVENTION RESEARCH EXPERTISE SURVEY AND CREATED A WEB-BASED TOOL THAT SROs CAN USE TO IDENTIFY METHOD TOLL GISTS FOR RECRUITMENT TO REVIEW PANELS, OFTEN A CHALLENGE. I CERTAINLY HAD THE EXPERIENCE OF BEING THE ONLY METHOD DOLL GIST ON REVIEW PANEL, THAT'S NOT GOOD FOR APPLICANTS OR REVIEW PROCESS SO WE NEED TO DO A BETTER JOB AND HOPE THIS TOOL WILL HELP. WE'RE OFFERING TRAINING TO ALL SROs ACROSS NIH BEGINNING IN 2018 TO LET THEM USE THAT TOOL. WE HAVE WEBINARS BROADCAST REGULARLY ON PREVENTION RESEARCH METHODS AND WE LAST YEAR ESTABLISHED EARLY STAGE INVESTIGATOR. GOING FORWARD WE WANT MAINTAIN CATALOGS OF EXISTING RESOURCES RELATED TO SCIENCE METHODS, PROVIDE RESOURCES TO REVIEW STAFF AND PROGRAM OFFICERS TO HELP DO A BETTER JOB GUIDING APPROXIMATE PRI CAN'TS AND DEVELOPING PREVENTION APPLICATIONS. AND OUR WEB PACE BATED TOOL AND RESEARCH METHOD RESOURCE WEBSITE A COUPLE OF THINGS WE'RE USING TO HELP IN THAT REGARD. WE WANT TO PROVIDE TRAINING IN PREVENTION SCIENCE METHODS TO PROGRAM AND REVIEW STAFF, NIH INVESTIGATORS AND THE EXTRAMURAL COMMUNITY. A FOURTH PRIORITY IS TO PROMOTE COLLABORATIVE PREVENTION RESEARCH PROJECTS. WHEN I WAS WORKING FOR 33 YEARS IN THE EXTRAMURAL COMMUNITY AS PROFESSOR FIRST AT MINNESOTA THEN UNIVERSITY OF MEMPHIS AND LAST AT THE OHIO STATE UNIVERSITY, I WAS ALWAYS SURPRISED HOW I AND COLLEAGUES COULD PUT IN ESSENTIALLY THE SAME APPROXIMATELY US COMULTIPLE ICEST JUST CHANGE THE VARIABLE AND ESSENTIALLY DO THE SAME RESEARCH MULTIPLE TIMES WITH FUNDING FROM MULTIPLE INSTITUTES. IT IS ALWAYS SEEMED TO ME THAT WE CAN DO A BETTER JOB IF WE COLLABORATED MORE AND JOINTLY FUNDED PROJECTS THAT HAD MULTIPLE OUTCOMES RATHER THAN SEPARATE PROJECTS AT EACH INSTITUTE. WE PROVIDE INPUT ON THE STRATEGIC PLANS DEVELOPED BY ICs. WE HAVE CREATED NEW SCIENTIFIC INTEREST GROUPS THIS PAST YEAR, CHILDHOOD SCREAMING ADULT SCREENING GENETICS OF PREVENTION, ENVIRONMENTAL AND POLICY LEVEL INTERVENTION, INTERVENTIONS TO PREVENT OR DELAY ONSET OF MULTIPLE CO-MORBID DISEASE. REPRESENTATIVES FROM NICHD SIT ON EACH OF THOSE SCIENTIFIC INTEREST GROUPS, VERY EXCITED ABOUT THAT. AND WE HOPE TO GENERATE NEW ACTIVITY IN THESE AREAS SOME WILL ADDRESS INSUFFICIENT EVIDENCE GAPS THAT THE USPSTF IDENTIFIED. OTHERWISE MOVE RESEARCH IN THESE AREAS FORWARD. WE WANT TO CONTINUE THIS WORK NEXT PERIOD, ADVANCE APPROACHES FOR LOOKING AT FUTURE RESEARCH LEADS AND PRIORITIES AN PREVENTION AND HIGHLIGHTING TRANS-NIH EFFORTS TO ADDRESS THOSE GAPS. WE WANT TO COORDINATE AND SUPPORT DEVELOPMENT OF COLLABORATIVE PREVENTION RESEARCH INITIATIVES TO ADDRESS GAPS. ANOTHER PRIORITY AS WE LOOK FORWARD IS O TO ADVANCE UNDERSTANDING AND PREVENTION RESEARCH. WHEN I GOT HERE IN 2012 PEOPLE APPROACHED AND SAID DAVID MOST THE THIS IS NATIONAL INSTITUTES PUBLIC DEFENDER'S OFFICE MED INSTITUTES OF MEDICINE RATHER THAN NATIONAL INSTITUTES OF HEALTH SO WE MADE EFFORT TO RAISE PROFILE OF PREVENTION RESEARCH NOT ONLY AMONG HEEDER SHEP BUT ACROSS THE -- LEADERSHIP BUT ACROSS THE CAMPUS AND WITH THE EXTRAMURAL COMMUNITY. WE EXPANDED OUR WEBSITE WHICH WAS QUITE PATHETIC WHEN I ARRIVED, IT LOOKED LIKE IT WAS CREATED IN 1970 THOUGH THE INTERNET DIDN'T EXIST AT THAT TIME. IT IS A ROBUST WEBSITE WITH LOTS OF USEFUL RESOURCES, WE STRENGTHENED PARTNERSHIPS WITH PROFESSIONAL SOCIETIES WE PRESENT AT SCIENTIFIC MEETINGS ON THE RESOURCES THAT WE'RE CREATING. WE POST INFORMATION AND INTERACTIVE TOOLS FOR PREVENTION RESEARCHERS FOR PROGRAM OFFICES AND DIRECTORS AND REVIEW STAFF. WE TRIED AND WILL CONTINUE TO TRY TO INCREASE VISIBILITY OF PREVENTION RESEARCH GOING FORWARD. WE'RE WORK, WITH AND COLLABORATING WITH STAKE HOLDERS TO COORDINATE ENHANCED COMMUNICATIONS ABOUT PREVENTION RESEARCH AND SUPPORTING ALL COMMUNICATION ACTIVITIES RELATED TO OTHER PRIORITIES. WHERE ARE WE IN DEVELOPMENT OF IN U PLAN? THE CURRENT ONE WHICH IS THE FIRST PLAN OFFICE EVER HAD WAS EARLIED IN 2014, IN THE LAST YEAR OF THAT FIVE YEAR PLAN. WE ARE PRESENTING NUMBER OF IC COUNCILS LAST FALL AND EARLY WINTER SO THAT PART OF THE PROCESS IS ONGOING. WE POSTED A DRAFT PLAN, ISSUED AN RFI, COMMENTS FROM THE PUBLIC ARE WELCOME THROUGH THE END OF JANUARY. WE WILL THEN TAKE THE INPUT WE GOT FROM ICs FROM THE COUNCILs FROM THE RFI AND REVISE THE PLAN PREPARE MILESTONES AND TIME LINES BY END OF MARCH, THEN PREPARE A STAFFING PLAN AND RESOURCE REQUEST BY END OF MAY AND TAKE TO THE DIRECTOR. THE DIRECTOR WILL CONTINUE TO BE FRANCIS COLLINS. I WAS NERVOUS NOT KNOWING WHO TO PRESENT THE REPORT TO AND DELIGHTED THAT IT WILL BE FRANCIS. WE EXPECT TO RELEASE THE FINAL PLAN IN TIME FOR THE BEGINNING OF FY 19. THAT IS IS THE END OF MY FORMAL PRESENTATION. I TRIED TO MOVE QUICKLY SO WE HAVE TIME FOR CONVERSATION AND WE DON'T KEEP YOU TOO LONG AWAY FROM LUNCH LATER TODAY. HOW CAN MY OFFICE BE OF HELP TO THIS INSTITUTE IN ADVANCING PREVENTION RESEARCH? ONE QUESTION. I'M VERY INTERESTED IN YOU ARE YOU THOUGHTS HOW WE CAN HELP YOU. HOW CAN WE BE OF HELP TO NICHD TO ADVANCE PREVENTION RESEARCH? ARE THERE OTHER PRIORITIES TO CONSIDER BESIDES THE FIVE I HAVE OUTLINED? ARE THERE THEMES TO CONSIDER APART FROM DRAFT PRY PRY PRIORITY? HAPPY TO PAUSE AND ENTERTAIN QUESTIONS AND GET YOUR INPUT ON PLANNING PROCESS. >> THANK YOU, DAVE. I THINK PEOPLE WORKING IN PREVENTION RESEARCH AREAS I KNOW WE HAVE SOME ON OUR COUNCIL. ARE THERE QUESTIONS YOU WANT TO ASK OF DAVID? >> OR SUGGESTIONS YOU WANT TO OFFER? >> DO YOU HAVE THE OPPORTUNITY TO WORK WITH FOUNDATIONS THAT ARE INTERESTED IN PREVENTION TO TRY TO LEVERAGE THEIR DOLLARS AND YOUR DOLLARS TO GO FURTHER? >> INTERESTING. >> APPROACH YOU TAKE TO STIMULATE MORE WORK IN THE AREA? >> INTERESTING SUGGESTION, NOT SOMETHING WE HAVE DONE TO DATE BUT I WILL TAKE THAT BACK TO MY TEAM AND WE WILL TALK ABOUT IT. WE HAVE FOCUSED PRIMARILY ON PROCESSES HERE AT NIH, HOW WE CAN MAKE PREVENTION RESEARCH NIH IS SUPPORTING BETTER QUALITY, BETTER FOCUSED MORE PRODUCTIVE. WE HAVE NOT BEYOND NIH GREATLY OTHER THAN TO SOME OF THE PROFESSIONAL SOCIETIES THAT ARE NATURALLY INTERESTED IN IN PREVENTION RESEARCH SO ABLE TO PUT THEM BUT WE HAVE NOT WORKED FOR EXAMPLE WITH GROUPS NATURALLY INTERESTED IN PREVENTION AND THAT'S A CERTAINLY SOMETHING WE CAN CONSIDER PURSUING NEXT PERIOD. >> WHAT ABOUT WORKING WITH THE CDC? SUPPOSEDLY THE NATION'S PREVENTION AGENCY. FOSTER RESEARCH PROGRAMS AS WELL. >> NIH IS THE NATION'S PREVENTION RESEARCH AGENCY. CDC IS THE NATION'S PREVENTION PROGRAMMING AGENCY. THEY NEED TO WORK HAND IN HAND, I VISITED CDC AFTER COMING HERE AND VISITING FOR DECADES AS ACADEMIC. WE DO WORK WITH THEM. WE ARE THE NIH LIAISON TO THE COMMUNITY PREVENTIVE SERVICES TASK FORCE WHICH CDC SUPPORTS WE INTERACT WITH THEM REGULARRY ON A VARIETY OF TOPICS, THEY SIT ON PREVENTION RESEARCH COORDINATING COMMITTEE. WE PARTICIPATE IN NUMBER OF ACTIVITYSTHEY ARE INVOLVED IN SO WE ARE INTERACTING INTERACTING WITH THEM REGULARLY. >> I CAN PROVIDE SUGGESTIONS ABOUT -- THE PRAGMATIC AND GROUP RANDOMIZED TRIALS, I'M REALLY GLAD TO SEE THAT YOU HAVE THIS COURSE ON THE -- ONLINE NOW. I SUPPOSE YOU ARE ALSO RESPONSIBLE FOR ANOTHER COURSE THAT WAS -- THAT FILLED UP QUICKLY SO I COULDN'T REGISTER ONE HURDLE IN MY EXPERIENCE IS AT THE INSTITUTIONAL REVIEW BOARD. THE REVIEW IRBs THAT REVIEW THIS RESEARCH. NOW MAYBE WITH THE SINGLE IRB NEIGHBOR A MOOT POINT BUT YOU CAN HELP BY ADVOCATING FOR INSTITUTIONAL REVIEW BOARDS OR MAYBE NCATS OR CTSAs CAN HELP WITH THAT APPROACH BECAUSE I STILL DON'T UNDERSTAND HOW TO DO COMPETITIVE EFFECTIVENESS, HOW TO DO GROUP RANDOMIZATION, CONSENTING PROCEDURE AND ALL OF THAT. >> CONSENTING GROUP CLUSTER RANDOMIZED TRIALS IS AN INTERESTING QUESTION. SOME TAKE THE VIEW THAT WHAT YOU GET THE CONSENT OF THE GROUP NAMELY THE WORK SITE OF THE CHURCH OR THE SCHOOL OR WHATEVER THE UNIT OF ASSIGNMENT IN SUCH A STUDY. TO PARTICIPATE IN THE TRIAL. THEN YOU HAVE TO GET CONSENT FROM PARTICIPANTS TO PROVIDE DATA. BUT NOT PARTICIPATE IN INTERVENTION. THAT TENDS TO BE THE WAY THINGS WORK IN THESE STUDIES AROUND THIS COUNTRY AND INTERNATIONALLY. GROUP IN CLUSTER RANDOMIZED TRIALS IS A SPECIAL TOPIC OF MINE, IT'S THE METHODS AREA THAT I WORKED IN MOST OF MY CAREER. SO YES, THAT COURSE IS NEAR AND DEAR TO MY HEART. WE HAVE ALSO CREATED A RESEARCH METHODS RESOURCES WEBSITE THAT WENT LIVE IN SEPTEMBER. IT'S DESIGNED TO HELP INVESTIGATORS INTERESTED IN PUTTING TOGETHER SUCH TRIALS AND THERE ARE LOTS OF RESOURCES THAT ARE AVAILABLE ON THAT WEBSITE TO HELP THEM INCLUDING SAMPLE SIZE CALCULATIONS TOOLS AND THINGS LIKE THAT. THERE ARE RESOURCES THERE THAT CAN BE HELPFUL TO PROGRAM OFFICERS AND DIRECTORS GUIDING INVESTIGATORS WHO ARE THINKING ABOUT THOSE KINDS OF STUDIES AND TO REVIEWERS THINKING WHO TO PUT ON PANELS. WE'RE ALSO WORKING WITH C SR AND WILL BE WORKING WITH THE INSTITUTES AND CENTERS ACROSS THE CAMPUS TO POINT THEM TO HEY, THESE ARE THE STUDY SECTIONS THAT SEEM TO BE GETTING MOST APPLICATIONS. YOU NEED TO BE SURE YOU HAVE THE RIGHT REVIEW EXPERTISE SO METHODS ARE CONSIDERED FAIRLY APPROPRIATELY DURING THE REVIEW PROCESS SO THOSE ARE THINGS WE WORK ON. I SIT ON THE IRB FOR ALL OF US PRECISION MEDICINE COHORT STUDY. WE HAVE NOT TAKEN ON ANY ACTIVITY TO TRY TO PROVIDE TRAINING OR EDUCATION FOR IRBs ACROSS THE COUNTRY RELATED TO THESE METHODS BUT YOU CAN POINT TO THAT WEBSITE I WAS TALKING ABOUT RESEARCH METHODS RESOURCES.NIH.GOV AND THEY'LL FIND ALL SORTS OF USEFUL INFORMATION THERE. >> ONE LAST QUESTION AND THANK YOU FOR GETTING US MORE OR LESS BACK ON TRACK. FIRST I WANT TO INTRODUCE OUR ACTING ASSOCIATE DIRECTOR FOR PREVENTION RESEARCH AT NICHD, THAT'S ROZ KING. CAN YOU RAISE YOUR HAND? SO MY QUESTION IS, HOW DOES YOUR OFFICE INTERACT WITH THE REPRESENTATIVES AT EACH OF THE INSTITUTES AND CENTERS? >> WE HAVE A PREVENTION RESEARCH COORDINATING COMMITTEE, BEEN IN EXISTENCE LONGER THAN MY OFFICE. IT CAME TO OFFICE AN BECAME PART WHEN THE OFFICE WAS CREATED IN 1985. THE PREVENTION RESEARCH COORDINATING COMMITTEE HAS REPRESENTATIVES FROM EACH OF THE INSTITUTES AND CENTERS, INCLUDING NICHD. AND HAS ALL ALONG. WE ALSO HAVE REPRESENTATIVES FROM AHRQ, CDC, FDA, SEVERAL PARTNERS WHOSE ACTIVITIES ARE VERY MUCH RELATED TO PREVENTION, THAT GROUP GETS TOGETHER NOT QUITE MONTHLY SEVEN OR EIGHT TIMES A YEAR, WE GENERALLY DON'T MEET IN THE SUMMER BUT OTHERWISE ALMOST MONTHLY AND WE TALK PANT ISSUES IMPORTANT TO ALL OF US, WE HEAR ABOUT THINGS GOING ON HERE, THAT ARE RELEVANT TO OUR THE OFFICE, WE PUSH OUT LOTS OF INFORMATION TO MEMBERS THAT WAY SO THERE'S COORDINATION WITH INSTITUTES AND CENTERS THROUGH THAT FORMAL CHANNEL. >> OKAY. THANK YOU, VERY MUCH. FOR THAT INFORMATIVE PRESENTATION. UP NEXT I WOULD LIKE TO WELCOME MY COLLEAGUE DR. NORA VOLKOW, DIRECTOR OF THE NATIONAL INSTITUTE OF DRUG ABUSE OR NIDA. WILL PRESENT TO US ON THE TIMELY TOPIC OF OPIOIDS AND PUBLIC HEALTH. SO WELCOME, NORA, TO NICHD. >> GOOD MORNING, EVERYONE, I WANT TO THANK DIANA FOR HAVING GIVEN ME THE OPPORTUNITY TO COME MEET WITH YOU COUNCIL BECAUSE THE NATIONAL INSTITUTE ON DRUG ABUSE WHILE NOT OBVIOUS HAS A LOT OF SHARED INTEREST AS IT RELATES TO WHAT Y'ALL DO IN THE INSTITUTES AND IN IN CHILD HEALTH AND DEVELOPMENT. IN FACT WE CAN CLEARLY STATE THAT THAT EARLY DEVELOPMENTAL STAGES OF THE HUMAN BRAIN ARE ONES MOST IMPORTANT TO BUILDING UP RESILIENCY OR THE VULNERABILITY FOR EMPERIMENT MENNATION WITH DRUGS OF USE AND ULTIMATELY FOR TRANSITION TO ADDICTION. I'M NOT GOING TO BE TOUCHING ANY OF THAT INSTEAD I WILL FOCUS ON THE OPIOID CRISIS BECAUSE I THINK THAT THIS IS AN OPPORTUNITY WHERE SCIENCE CAN COME UP WITH SOLUTIONS THAT ARE INCREDIBLY RELEVANT NOT ONLY IN CONTAINING THE PRIZES VERY IMPORTANTLY IN OPTIMIZING THE OUTCOMES OF ALL OF THOSE INDIVIDUALS THAT EITHER ACTIVELY OR PASSIVELY ARE BEING EXPOSED TO OPIOIDS. SO HOW -- WHAT IS THE NATURE OF THE CRISIS AND HOW BAD IT IS? THIS SLIDE THIS IS THE MAP OF THE UNITED STATES USING COLOR SCALE TO INDICATE NUMBER OF FATALITIES ASSOCIATED WITH OVERDOSES BY EVERY HUNDRED THOUSAND INDIVIDUALS AND HOW THAT HAS DRAMATICALLY INCREASE SINCE 1999 TO 2015. IN 1999 WE SEE TWO SPOTS IN THE UNITED STATES WITH HIGH RATES OF OVERDOSE FATALITIES ONE IN NEW MEXICO, THE OTHER IN THE MIDDLE OF APPALACHIAN REGION. IF YOU MOVE 16 YEARS FROM THERE YOU CAN SEE THESE GEOGRAPHY YOU CAN SEE HOW DEVASTATING IT IS. YOU'RE NOT ABLE BECAUSE PHONES ARE SMALL BUT EVEN OUR -- THRESHOLD FOR WHAT RED COLORS ARE HAD TO BE INCREASE BECAUSE WE NOW HAVE COUNTIES IN THE UNITED STATES WHERE RATE OF OVERDOSE FATALITIES OVER 40 PER 100,000 INDIVIDUALS SO NOT JUST DISPERSING BUT ALSO IN TERMS OF MAGNITUDE OF THE CONSEQUENCES FROM THOSE FATALITIES. THIS IS 2015. I HAVE BEEN TRYING TO GET THIS DATA FROM CDC 2016, 2016 WE KNOW FROM THE NUMBERS SHOW 22% INCREASE IN OVERDOSE FAY TAILS FROM 2015. SO HIGHLIGHTING THE NOTION IN IS NOT A CRISIS UNDER CONTROL NOT AT ALL, I WANTED THE MAP BECAUSE I COULD ONLY TELL YOU, 22%, Y'ALL CAN SEE IT. GEOGRAPHY IS CHANGING, I'M CURIOUS BECAUSE 2016 MAP YOU WILL SEE THE -- ALSO PLOT WITH RED. WE HAVE SEEN IN SOME OF THESE STATES DOUBLING NUMBER OF FATALITIES IN OVERDOSES OVER A TWO YEAR PERIOD. WHICH IS REFLECTING THE CHANGING NATURE OF THESE OPIOID CRISIS. BEING DRIVEN AND FUELED BY ACTUALLY DIVERSION OF SYNTHETIC OPIOIDS IN PARTICULAR FENTANYL AND SOME OF THESE ANALOGS WHICH ARE USED TO LACE HEROIN OR PRESCRIPTION BECOME DIRECTLY SEEKING THE VERY INTENSE EFFECTS OF THESE DRUGS. THAT HAS BASICALLY STARTED THROUGH THE NORTH EASTERN STATES. IT'S VERY DRASTIC SITUATION THAT WE CURRENTLY HAVE, 2016 NUMBERS FROM CDC WORTH 64,000 FATALITIES FROM OVERDOSE AND THAT IS MUCH HIGHER THAN PEEK OF FATALITIES FROM CAR ACCIDENTS, PEAK OF HIV EPIDEMIC SO IT'S DEVASTATING AND THE OTHER ISSUE THAT'S WORRISOME IS NOT CONTROLLING IT. WHAT IS GENERATING IT? USING ANOTHER MAP, THIS IS A MAP OF THE BRAIN THAT SHOWS A LOCATION, USING THE SAME SCALE FOR HIGH TEMPERATURE HIGH CONTENT NOT FOR LOCATION OF MU OPIOID RECEPTORS IN THE HUMAN BRAINS POSITRON OMISSION TOMOGRAPHY, WHAT YOU CAN SEE IS THAT THE DISTRIBUTION IS QUITE WIDESPREAD BUT THERE ARE SOME AREAS WITH HIGH CONTENT. I'M PUTTING ARROWS TO THOSE AREAS FOR THOSE THAT MAY NOT -- TO THE BRAIN, THAT'S VERY HIGH CONTENT ON THE ACC, ANTERIOR SINGLE HR WHICH IS A KEY AREA FOR PROCESSING PAIN, OTHER KEY AREA IS ACTUALLY ACTS LIKES A FILTERING PROCESS OF PAIN SIGNAL AND AREA OF THE BRAIN, ONE OF THE MAIN PLACES YOU ARE INHIBITING PAIN RESPONSES. THEY ARE LOADED WITH OPIOID RECEPTORS. THIS IS WHY OPIOID DRUGS ARE POTENT MEDICATIONS WE HAVE FOR MANAGEMENT OF AUSCULT PAIN RIGHT AWAY. YOU CAN SEE IT'S MAGICAL. UNFORTUNATELY THAT WORKING IN A SITUATION IS NOT AS GOOD FOR CHRONIC PAIN BECAUSE YOU BECOME TOLERANT SO YOU REQUIRE HIGHER AND HIGHER DOSES, NOT ALL THE PAIN CONDITIONS RESPOND TO OPIOIDS. NONETHELESS BECAUSE THERE ARE NOT MANY FOR MANAGEMENT OF PAIN THAT LED TO THE OVERPRESCRIPTION. OBJECTED OTHER HAND, THE -- WHICH HAS HIGH CONTENT OF MU OPIOID RECEPTORRERS IS A KEY CENTER OF THE REWARD IN THE HUMAN BRAIN. ALL DRUGS THAT PRODUCE ADDICTION ACTIVATE THAT SYSTEM AND SO DO OPIOIDS. THAT REDUCE TREATMENT OF PAIN. THIS LIES SOME OF THE DIFFICULTIES THAT WE HAVE WITH THESE DRUGS. THEY CAN BE EXTRAORDINARY AND WHEN USED PROPERLY FOR ACUTE PAIN, THERE ARE ALMOST SOME OF THE MOST REWARDING AND ADDICTIVE SUBSTANCES OF ABUSE. THE OTHER ISSUE ON THESE IS THERE'S HIGH CONCENTRATION OF MU OPIOID RECEPTORS ON THE BRAIN STEM AREAS THAT REGULATE BREATHING WHICH POSES ANOTHER ONE OF THE MAJOR CHALLENGES THAT WE HAVE WITH THESE DRUGS THAT WHEN THEY GET ACTIVATED BY AGONIST DEPRESS RESPIRATION WHICH IS ACCOUNTING FOR THE HIGH MORTALITY THAT WE SEE WITH UTILIZATION OF THESE DRUGS WHETHER PAIN MANAGEMENT SEEING OVERDOSES AND FATALITY IT IS OR WHERE IT IS BECAUSE YOU ARE ABUSING THEM AND YOU BECOME ADDICTEDDED TO THEM. WE ARE ALSO SEEING FATALITIES FROM RESPIRATORY DEPRESSION. SO AS A STRATEGY THAT WE HAVE BEEN FOLLOWING FOR MANY YEARS BECAUSE THIS IS NOT A CRISIS THAT JUST EMERGE IN THE PAST TWO YEARS, WE HAVE BEEN AWARE OF THIS SIGNIFICANT INCREASES IN PROBLEMS EMERGE SINCE 2003 WHICH IS WHEN I CAME TO NIDA 15 YEARS AGO T. IT IS CLEAR THE CRISIS WAS EMACIATED BY OVERPRESCRIPTION OF OPIOID MEDICATIONS AND YOU CAN TRACE IT QUADRUPLED OVER PERIOD OF 15 TOO 20 YEARS, SECONDARY TO STRONG PUSH FOR WHAT WAS VERY GOOD INTENTION MANAGEMENT OF PAIN ON PATIENTS SUFFERING FROM PAIN CONDITIONS THAT LED TO OVERPRESCRIPTION OF OPIOIDS AND THE LACK OF UNDERSTANDING ACTUALLY, I WILL SAY COMPLACENCY OF HEALTHCARE SYSTEM IN ACTUALLY BELIEVING THAT OPIOIDS WERE SAFE, AND I SAY COMPLACENCY BECAUSE WE KNEW WHEN THIS WAS HAPPENING IN THE '90s, OPIOIDS WERE ADDICTIVE AND WE CERTAINLY KNEW THE DIFFERENCE BETWEEN THERAPEUTIC DOSE AND OVERDOSE WAS NOT VERY LARGE SO WE KNEW THEY WERE DANGEROUS. THERE WAS A STRONG CAMPAIGN TO ACTUALLY TREAT PATIENTS THAT WERE SUFFERING FROM PAIN AND THE NOTION THAT HAS WHEN YOU HAVE PAIN, WE WERE TALKING MEDICAL SCHOOL, SOME MEDICAL SCHOOLS MAYBE STILL TEACHING THIS, IF YOU HAVE PAIN AND GET OPIOID MEDICATION YOU'RE NOT GOING TO BECOME ADDICTED TO IT. THAT HAS BEEN PROVEN TO BE WRONG AS WE SEE PATIENTS BECOMING ADDICTED TO PAIN MEDICATION AND THE OTHER TOO BELIEVING YOU CAN INCREASE THE DOSE AS YOU DEVELOP TOLERANCE AND JUST INCREASE THE DOSE, IT'S SAFE, THE TOLERANCE WILL PROTECT THE PATIENT. THE PROBLEM IS THAT THE LEVEL OF TOLERANCE OF THE DIFFERENT NEUROCIRCUITS IS APPEARS AT DIFFERENT TIME LINES. YOU NEVER DEVELOP TOLERANCE TO CONSTIPATING EFFECTS OF OPIOIDS BUT YOU WILL DEVELOP TOLERANCE RAPIDLY TO THE ANALGESIC EFFECTS. SO WHEREAS THE EFFECTS ON THE RESPIRATORY CENTER ARE SLOWER AND THEN THAT AGAIN POSES THE RISK OF WHY YES, INDEED A PATIENT WITH VERY HIGH DOSES AND WE NOW KNOW FROM CLEARLY STIPULATED ON THE CDC GUIDELINES, YOU HAVE MORE THAN A HUNDRED MILLIGRAMS MORPHINE EQUIVALENT YOUR RISK FOR OVERDOSE ARE SIGNIFICANTLY HIGHER. IN FACT I YOU START TO SEE SIGNIFICANT INCREASES AROUND 50. WHY AM I DEGREE BRINGING THIS UP? PUTTING IN THE TOP OF TRIANGLE BECAUSE WE ARE ADDRESSING THE OPIOID CRISIS WE NEED TO ADDRESS THE NEED OF BETTER INTERVENTIONS FOR MANAGEMENT OF CHRONIC PAIN CONDITIONS. IF E DON'T DO THAT PAIN CAN BE DEVASTATE AND IT'S A PREVALENT CONDITION, WE WILL HAVE A BLACK MARKET FOR USE OF OPIOIDS EVEN IF WE MAKE THEM ILLEGAL. BECAUSE OF THE NEEDS OF PATIENTS WITH PAIN. SO WE NEED TO ADDRESS THAT. AT THE BASE, THE TOPICS THAT RELATE DIRECTLY IMMEDIATELY TO THE ADDICTION, ONE OF THEM IS THE INTERVENTIONS THAT CAN LEAD US TO PREVENT AND TREAT ADDICTION WHEN IT HAPPENS. AND THE OTHER ONE IS HOW DO WE INTERVENE PREVENT OVERDOSES OR REVERSE OVERDOSES. IN THIS PORTFOLIO I DON'T HAVE MUCH TIME BUT LIKE ANYTHING ELSE WE DO AT THE NIH, HAS A VERY BASIC COMPONENT TO UNDERSTAND THIS PROCESS, THEN TRANSLATIONAL COMPONENT WHICH HELP TAKE KNOWLEDGE AND DEVELOP INTO PROBLEMS INCLUDING MEDICATIONS. ALSO THEN IT HAS AN IMPLEMENTATION COMPONENT, SERVICES RESEARCH COMPONENT, WE KNOW THESE WORKS TREATING PEOPLE ADDICTED TO OPIOIDS WITH MEDICATION IMPROVES A ALLOT MILLION P LEVELS BUT HOW DO WE IMPLEMENT WHEN THERE'S NOT SUFFICIENT PROGRAMS OUT THERE IN THE IMMUNITY TO TAKE CARE OF THE PATIENTS. FROM SO HOW DO WE DEVELOP MODELS THAT ARE DEPLOYED TO HELP THESE PATIENTS. SAME PERTAINS TO ISSUE OF OVERDOSE REVERSAL. VERY IMPORTANTLY, OVERDOSE PREVENTION. ONE THING WE KNOW AFFECTS OF OPIOIDS AND RESPIRATORY SYSTEM IN GENERAL THAT CAN HELP PEOPLE IN DYING, FROM THESE MEDICATION MEDICATIONS. SO IN THE AREA OF PAIN, THERE ARE MULTIPLE INSTITUTES THAT GET ENGAGED IN BASIC NEUROSCIENCE OF PAIN OR PERIPHERAL MECHANISM UNDERLYING PAIN. THE MAIN -- BASIC NEUROLOGIST TAKES THE LEAD IN TERMS OF IT REPRESENTING THE NIH AS RELATES TO PAIN BUT MANY INSTITUTES INCLUDING NIDA PUT SIGNIFICANT RESOURCES IN DEVELOPING ALTERNATIVE STRATEGIESES THAT ARE NOT ADDICTIVE FOR MANAGING PAIN. WE FOCUS ON STRATEGIES THAT RELATE GOING TO BE OPIOID SPARING OR ANALGESICS THAT ARE NOT GOING TO BE ADDICTIVE. WE WORK WITH NEUROTRANSMITTER SYSTEMS, TWO MOST PAID ATTENTION ENDOGENOUS OPIOIDS AND ENDOGENOUS CANNABINOIDS, WHICH IS IMPORTANT BECAUSE WE SEE INCREASED UTILIZATION OF MARIJUANA FOR TREATMENT OF PAIN WITHOUT SUFFICIENT EVIDENCE ABOUT ITS EFFECTIVENESS. WE AS AN AGENCY NEED TO UNDERSTAND WHERE ARE THE ACTIVE INGREDIENTS AND HOW TO PROVIDE THEM TO PATIENTS IN A SAFE WAY. I'M JUST ILLUSTRATING YOU WHY BASIC SCIENCE IS SO IMPORTANT IN THIS WHOLE ISSUE OF THE PRIZES AND HOW IT CAN REALLY BE TRANSFORMATIVE IN THE WAY WE DEAL WITH A PROBLEM. SO FOR MANY YEARS PHARMACEUTICALS HAVE INVESTED MILLIONS AND MILLIONS OF DOLLARS TO GET THAT WHAT I CALL THE PANACEA. OPIOID THAT IS NOT ADDICTIVE, OPIOID WITH LESS RESPIRATORY DEPRESSING EFFECT AND THEY FAIL. FAIL, FAIL. SO THEY CUP THEIR INVESTMENTS INTO AMBITIOUS GOAL, OPIOID SO EFFECTIVE IN ANALGESIA BUT NOT ADDICTIVE. WE UNDERSTAND THE THREE DIMENSIONAL STRUCTURE OF MU OPIOID RECEPTOR RESEARCH THAT'S GONE BEYONDS DESCRIBING THIS OPIOID RECEPTOR IN THE MEMBRANE BUT WHEN BOUND TO DIFFERENT TYPE OF LIGANDS, RESEARCHERS HAVE COME TO REALIZE THAT DEPENDING ON THE -- HOW LIGANDS SIT IN THAT RECEPTOR YOU CAN DIFFERENTIALLY ACTIVATE DISTINCT INTRACELLULAR SIGNALING PATHWAYS. TWO RELEVANTABLE WHAT WE'RE DEALING NOW NOT THE ONLY ONES BUT SALIENT IS G PROTEIN PATHWAY. BECAUSE THAT ONE IS THE ONE RESPONSIBLE FOR ANALGESIA. YOU HAVE THE BETTER RESTING PATHWAY, INVOLVE AMONG OTHER THINGS IN THE INTERNALIZATION OF THE OPIOID RECEPTOR, THAT IS ASSOCIATED WITH SIDE EFFECTS. NOTABLE DECREASE RESPIRATORY DEPRESSANT EFFECTSES OF OPIOIDS AS WELL AS CONSTIPATING DECREASING ACTIVITY OF GI FUNCTION. AND SOME HAVE CLAIMED THAT BETA REST TIN PATHWAY IS INVOLVED IN REWARDING EFFECT OF OPIOID. IDON'T THINK THAT EVIDENCE IS VERY STRONG BUT CERTAINLY WITH RESPECT TO THE OTHER ONES, IT IS. SO PHARMACEUTICAL COMPANIES RESEARCHERS ARE OPTIMIZING THE DEVELOPMENT OF CHEMICAL STRUCTURE THAT WILL BIND INTO THAT RECEPTOR AND ACTIVATE ONLY G PROTEIN, NOT THE OTHER SIGNALING CASCADE I'M PUTTING IT THERE BECAUSE THESE PARTICULAR ANALGESIC IS PHASE 3 CLINICAL TRIALS AND IT IMPROVES EFFECTIVE, INCENTIVIZE MANY OTHER PHARMACEUTICALS TO GO INTO THE DEVELOPMENT OF THIS AREA. I HIGHLIGHT BECAUSE IT SHOWS YOU BY KNOWLEDGE BASIC KNOWLEDGE YOU CAN ACTUALLY FINALLY ADDRESS AND COME UP WITH SOLUTIONS OF PROBLEMS THAT OTHERWISE HAVE BEEN UNSUCCESSFUL. THIS IS PAIN AT THE TOP, NOW GOING TO GO DHAL CHALLENGES, REVERSING OVERDOSESES. WE'RE LUCKY PHARMACOLOGICAL. WE HAVE ANING A TAGNIST THAT GETS INTO RECEPTOR RAPIDLY AND EXTRAORDINARY HIGH AFFINITYNA LOCK ZONE. IT'S SO -- NALOXONE. IF YOU HAVE SOMEONE OVERDOSE FROM HEROIN AND YOU GIVE THEM NALOXONE IT WILL PUSH THE HEROIN OUT OF THE OPIOID RECEPTOR INTERFERING WITH RESPIRATORY DEPRESSING EFFECTS OF HEROIN AND THE PATIENT STARTS TO BREATHE AGAIN. AND IT WORKS. THE CHALLENGE IS NUMBER ONE, YOU NEED TO ADMINISTER RIGHT AWAY BECAUSE IF A PATIENT HAS BEEN BASICALLY STOP BREATHING FOR FIVE OR SIX MINUTES YOU WILL START TO HAVE BRAIN DAMAGE SO YOU NEED TO GIVE IT RIGHT AWAY AND YOU NEED TO GIVE IT IN A ROUTE OF ADMINISTRATION THAT WILL RESULT IN HIGH CONTENT IN THE PLASMA. PLASMA. SO THERE IS ONE OF THE MAJOR CHALLENGESES THE OTHER CHALLENGE WE SEE TOO IN REVERSAL OF THIS OPIOID OVERDOSES IS THAT WE'RE STARTING TO SEE MORE AND MORE CLINICAL REPORTS IN THE LITERATURE AS WELL AS BASICALLY FROM THOSE FIRST BY STANDARDS THAT NALOXONE IS NO LONGER ABLE SUFFICIENT TO REVERSE OVERDOSES. THEY NEED TO ADMINISTER SOMETIMES FIVE OR SIX DIFFERENT INJECTIONS AND SOMETIME THEY CANNOT ACTUALLY REVERSE NOSE PATIENTS THAT HAVE OVERDOSE. ONE OF THE CONCERNS IS WHILE DIFFICULTY OF REVERSING PATIENTS RELATE TO THE FACT THESE INDIVIDUALS ARE OVERDOSING WITH THIS DRUG. FENTANYL IS 100 TIME MORE POTENT THAN PROTEIN AND SOME INSTANCE BEING ACTUALLY REPORTS OF UNLACING OF HEROIN WITH FENTANYL. FEN NIL IS USED FOR ANESTHETIZING EXTRAORDINARY POTENT, TO CONCEPTUALIZE BUT IN THIS GRAPH IT'S BASICALLY 10,000 TIMES MORE POTENT THAN MORPHINE. YOU CAN IMAGINE HOW DIFFICULT IT IS ACTUALLY TO DOSE SOMEONE PRECISELY MEASURE. EXTRAORDINARY HIGH RATE OF OVERDOSE FATALITIES, FENTANYL EVEN MORE SO. NALOXONE CAN PUSH THE HEROIN OUT BECAUSE OF HIGH AFFINITY, THESE DRUGS ARE NOT STRAIGHT FORWARD BECAUSE THEIR AFFINITY IS TIGHT AND PHARMACOKINETICS, DURATION OF ACTION IS LONGER LASTING SO WE AS AGENCY ARE ADDRESSING THE NEED TO DEVELOP OTHER MEDICATIONS THAT CAN BE EFFECTIVE IN THESE DRUGS. FENTANYL, WHY? BECAUSE IN MASSACHUSETTS ESTIMATED 50% OF OVERDOSES RIGHT NOW WERE ASSOCIATED WITH FENTANYL SO A MAJOR CHALLENGE THE OTHER CHALLENGE WE HAVE IS PEOPLE ARE OVERDOSING WITH MULTIPLE DRUGS. SO AT LEAST 15% OVERDOSES WITH DRUGS ARE WITH ALCOHOL, 15% WITH BENZODIAZEPINES AN THOSE DRUGS WILL NOT REVERSE WITH ANTAGONIST. THE NOTION ABOUT WHAT IS IT YOU CAN DO. THIS IS AN EXAMPLE OF SOME OF THE THINGS WE HAVE DONE IN THIS CASE A SUCCESSFUL DRUG, PARTNER WITH PHARMACEUTICALS TO GET THAT TRANSLATIONAL COMPONENT THAT WE HAVE SOMEONE RESEARCHER HOW DO WE TRANSLATE IT AND IT'S ACTUALLY THE BIG CHALLENGE OF BEING ABLE TO DELIVER NALOXONE VERY HIGH CONTENT BY SOMEONE THAT IS -- DOES NOT KNOW HOW TO INJECT. SO THIS IS A NASAL NARCAN, LEADS TO THE SAME LEVEL OF BLOCKADE THAT YOU SEE WITH INJECTABLE NALOXONE. THIS PRODUCT WAS APPROVED BY FDA LAST YEAR. AND IS NOW THE MAIN PRODUCT IN UTILIZED TO REVERSE OVERDOSES RIGHT NOW OR CHALLENGE IS THESE PARTICULAR PRODUCT IS NOT BEING SUFFICIENT IN REVERSING OVERDOSES SO WE ARE WORKING WITH A PHARMACEUTICAL HIGHER DOSES LONGER LASTING TYPE OF ANTAGONIST. FINALLY I WANT TO END UP IN TERMS OF THAT TRIANGLE WITH ISSUE OF MEDICATIONS FOR PEOPLE THAT BECOME ADDICTED, WHEN YOU DO MEDICATION AND WE HAVE BUPRENORPHINE MALL LOCK ZONE, THEY REDUCE OVERDOSE DEATHS CRIMINAL ACTIVITY AND DETECTING DISEASE TRANSMISSION, IMPROVE SOCIAL FUNCTIONING, RETENTION AN TREATMENT AND IMPROVE OUTCOMES ON NEWBORNS WITH NEONATAL (INAUDIBLE) SYNDROME. I'LL TOUCH ON THAT AGAIN BECAUSE THIS IS VERY RELEVANT FOR THIS INSTITUTE. NOW, SO IF WE HAVE THOSE MEDICATIONS WHAT ARE THE ISSUES, WHY NOT JUST BE HAPPY AND SAY LESS THAN SURE PATIENTS BECOME ADDICTED GET -- WELL, THAT'S THE FIRST CHALLENGE. NUMBER TWO, THERE'S STIGMA SO MANY OF THE HEALTHY SYSTEMS WANT THE USE THEM, MANY OF THE SUBSTANCE TREATMENT PROGRAMS WANT TO USE THEM, THOUGH THEY HAVE A LARGE EFFECT SIZE IN TERMS OF BENEFIT, 50% OF PATIENTS WILL RELAPSE WITHIN SIX MONTHS. SO THERE IS A NEED FOR ADVANCING. WE DON'T WANT TO ADVANCE TO NEW MEDICATIONS, SAY THIS ALREADY ARE VERY POWERFUL TOOLS. HOW ARE WE AS A NATION? SO LOOK AT THE OPIOID USE AT THIS ORDER CASCADE, FOR UTILIZATION AND TREATMENT OF THE INDIVIDUALS WHERE WE KNOW THE EVIDENCE SHOWS THAT IT'S ACTUALLY QUITE BENEFICIAL. THE RED IS MORE OR LESS ESTIMATE OF WHERE WE ARE. LIKELY TO BE UNDERESTIMATION OF THE NUMBER OF CASES. BUT LET'S BE CONSERVATIVE. AND THE BLUE IS WHERE WE ARE IN TERMS OF CASCADE OF CARE. DIAGNOSIS, WE ARE MORE OR LESS OKAY, BASICALLY IN TERMS OF TOTAL NUMBER. AS WE GO DOWN THE LINE WE SEE ENGAGING CARE, 600,000, INITIATION OF MEDICATION ASSISTED TREATMENT 300,000. RETAIN SIX MONTHS, YOU WANT TO RETAIN SIX MONTHS, IF YOU DON'T YOUR RISK OF OVERDOSE ARE VERY, VERY HIGH. APPROXIMATELY 200,000. AND THEN CONTINUE -- WHICH IS WHAT YOU NEED TO HAVE THE BEST OUTCOMES. LESS THAN A HUNDRED THOUSAND SO A HORRIBLE GAP IN CASCADE OF CARE SO WITHOUT MEDICATION THESE IMPORTANCE OF ADDRESSING THESE, THIS IS AGAIN I'M GOING TO HIGHLIGHT BECAUSE THE OUTCOMES ARE NOT MUCH BETTER, INCREDIBLY -- SIGNIFICANTLY BETTER FOR THE PERSON ADDICTED, BUT IN THE CASE THAT ON A MOTHER THAT IS PREGNANT THEY'RE MUCH BETTER FOR THE INFANT BORN OUT OF THE MOTHER THAT IS BEING TREATED THAN ONE THAT IS NOT. FROM SO ONE THING WE OOH TRYING TO DO IN TERMS OF ADDRESSING THIS WHOLE ISSUE THAT YES, THEY ARE, BUT RELAPSES RATES ARE VERY HIGH. WE HAVE TO MAKE A DECISION EVERY DAY TO TAKE THEIR MEDICATION. SO WE KNOW IN MEDICINE ONE OF THE LOW HANGING FRUIT IS EXTENDED RELEASE FORMULATIONS. AND SIGNIFICANTLY BY THEMSELVES IMPROVE COMPLIANCE. SO SO CREATED PARTNERSHIPS, NIDA HAS A LONG, LONG HISTORY OF CREATING PARTNERSHIPS, PROVIDING GRANTS WITH PHARMACEUTICAL INDUSTRY SO THEY CAN BRING THE PRODUCTS INTO THE MARKET RISKING COMPOUNDS SO THEY CAN TAKE THEM. ONE AREA HAS BEEN ON THE EXTENDED RELEASE FORMULATIONS, AND THIS IS OUR TWO EXAMPLES, THE VERY SUCCESSFUL PRODUCT. ONE IS NALTREXONE EXTENDED RELEASE ONCE A MONTH. AND THE OUTCOMES ARE BETTER. THE AFFECT SIZES ARE VERY LARGE. THE OTHER ONE IS RECENT ONE THAT WAS APPROVED AGAIN LAST YEAR ALSO. BUPRENORPHINE IMPLANT THAT LASTS SIX MONTHS. COVERING THE INDIVIDUAL FOR A PERIOD OF TIME WHERE THEY'RE ACTUALLY VERY VULNERABLE FOR RELAPSE AND OVERDOSING. THE ISSUE UNFORTUNATELY WITH THESE BUPRENORPHINE IMPLANT IS THE MAXIMAL ALLOWED DOSE IS IN MILLIGRAMS WHICH IS A LOW DOSE OF BUPRENORPHINE SO FEW PATIENTS CAN BE SUSTAINED ON 8-MILLIGRAM DOSE. CURRENTLY THERE'S TWO NEW PRODUCTS COMING UP WITH PHARMACEUTICALS WE WORK WITH. AND PROVIDE ONE MONTH BUPRENORPHINE INJECTABLE THAT LEADS TO VERY, VERY HIGH CONCENTRATIONS OF BUPRENORPHINE IN BLOOD AND FACILITATE COMBINES BUT ALSO ALLOW US TO TREAT PATIENTS THAT ARE ON DIFFICULT TO REACH COMMUNITIES LIKE RURAL COMMUNITIES WHERE THERE'S NOT ACCESS TO PHYSICIAN OR HEALTHCARE SYSTEM WHERE THE PATIENT CAN GO ON A DAILY BASIS. BASIC VERGE, ALSO AN -- AGAIN, IS WHERE WE AT THE END OF THE DAY COME UP WITH SOME OF THE MOST INTERESTING OPPORTUNITIES FOR ADDRESSING DISEASES THAT WORK WITH IN OUR CASE ADDICTION. SO UNDERSTANDING NEUROBIOLOGY OF THE CHANGES IN THE BRAIN, OF ADDICTION, IS LEADING US TO ACTUALLY TARGET SPECIFICS OF INTERVENTIONS FOR STRENGTHENING CIRCUITS DAMAGED BY EFFECTS OF DRUGS. ALSO VERY NOVEL WAYS TRYING TO ADDRESS PROBLEM OF ADDICTION WHICH IS ACTUALLY WHAT I CALL THE SCIENCE THAT WILL TAKE A LONG TIME NOT IMMEDIATE ONE PERHAPS TAKE TEN YEARS BUT IF IT WORKS IT COULD BE TRANSFORMATIVE. THE ISSUE, THE DEVELOPMENT OF VACCINES AGAINST HEROIN, VACCINES AGAINST FENTANYL THAT CREATE ANTIBODIES AGAINST THESE DRUGS SO SUCH THAT WHEN THE PERSON INJECT IT IS DRUG THE ANTIBODIES BIND TO AT THIS TIME AND THE DRUG CANNOT GET INTO THE BRAIN. SO YOU PREVENT REINFORCING EFFECTS OF THE DRUG TO PREVENT OVERDOSES BECAUSE THAT DRUG NEVER MAKES IT TO THE BRAIN. IT WORKS MARVELS IN THE RATS. WHICH IS TO BRING THIS TYPE OF DEVELOPMENT IN TO HUMANS WHERE ANGIOGENICITY IS NOT AS STRONG AS WHAT YOU GET BUT THERE IS VERY INTERESTING DRUGS ONGOING, SOME ABOUT TO START -- ACTUALLY STARTED PHASE 2 CLINICAL TRIALS FOR VACCINE. THEN THERE'S ASPECT OF SCIENCE THAT WE CALL IMPLEMENTATION AND SERVICES THAT AGAIN WAS DISCUSSING BEFORE WHICH IS TO TRY TO ADDRESS, WE DON'T HAVE THEM HERE PEOPLE DYING EVERY SINGLE DAY. ACTIVE SPEAKING BASICALLY TWO PEOPLE OVERDOSED AND DIED SO THERE IS URGENCY WHAT WE DO. THE ISSUE U.S. WHAT IS IT WE CAN DO THAT CAN ACTUALLY TREATMENT BASED ON EVIDENCE THAT CAN IMPROVE OUTCOMES MAY NOT BE SUFFICIENT TREATMENT PROBLEMS FOR ADDICTION BUT THERE'S HEALTHCARE SYSTEM ALL OVER THE COUNTRY. SO WE ARE TARGETING OUR INVESTMENTS ON IMPLEMENTATION SCIENCE ON THE ONE HAND ON THE HEALTHCARE SYSTEM, THE OTHER IN THE CRIMINAL JUSTICE SYSTEM. THE HEALTHCARE SYSTEM MAKES ENORMOUS AMOUNT OF SENSE BECAUSE MANY PATIENTS END UP THERE AND PHYSICIANS IS PLAY AN IMPORTANT ROLE IN SCREENING INDIVIDUALS SUFFERING FROM OPIOID ADDICTION. THIS IS AN EXAMPLE OF A POOLED RESEARCH THEY SHOW VERY SIMPLE INTERVENTION, EMERGENCY DEPARTMENTS YOU GET PATIENTS OVERDOSING YOU GIVE THEM NALOXONE. INSTEAD OF RELEASING OUT THROUGH THE DOOR WHAT HAPPENS IN MOST EMERGENCY DEPARTMENT IN THE UNITED STATES, AND HERE IS WHAT HAPPENS A PATIENT IMMEDIATELY GOES AND TAKES THE OPIOID AND GOES BACK AND OVERDOSE. INSTEAD OF DOING THAT, THAT HAS A HIGH MORTALITY RATE, WHAT THEY DECIDED FROM COLLEAGUES AT YALE UNIVERSITY, BUPRENORPHINE, YOU INITIATE THAT THERE AND REFER THEM TO TREATMENT GAIN SOME TIME, GET THE PATIENT RIGHT THERE INITIATED ON MEDICATION THAT WILL INDECREASE CRAVING AND WITHDRAWAL. THAT SIMPLE INTERVENTION BUPRENORPHINE VERSUS BRIEF INTERVENTION SIGNIFICANTLY GROUP OUTCOMES AND THIS IS RELATED TO THE USE OF OPIOIDS DECREASE VISITS TO EMERGENCY DEPARTMENT AND THEY INCREASE RETENTION AN TREATMENT. THEY FOLLOW THIS INDIVIDUAL, THIS WAS SEVEN DAYS NOW THEY HAVE DATA AT ONE AND TWO MONTHS SHOWING THAT INDEED IS STAINING. ALSO INTERESTING BECAUSE NOW THAT WE HAVE THE ONE MONTH EXTENDED BUPRENORPHINE, THAT YOU WILL MAKE IT MUCH EASIER FOR PHYSICIANS TO BE ABLE TO UTILIZE IT. SIMILAR PROJECTS ARE GOING ON TO TRY TO INITIATE TREATMENT IN THE CRIMINAL JUSTICE SYSTEM BEFORE A PERSON LEAVES FREE ZONE OR JAIL AND THAT WAY PREVENT FROM OVERDOSING WHICH IS AGAIN, A VERY HIGH RISK PERIOD FOR OVERDOSING BECAUSE THE PATIENTS HAVE BEEN IN PRISON, THEY HAVE NOT BEEN TREATED, THE FIRST THANK THEY GO IS TAKE DRUGS. THEY DON'T HAVE TOLERANCE SO THEY OVERDOSE. END UP MY PRESENTATION WITH THIS ONE, AS SAID YES WE ARE FOCUSING A LOT OF EFFORT INTO THE PEOPLE THE PERSON THAT IS TAKING THE DRUGS, WHEN IT COMES TO WOMEN THERE IS A SIDE EFFECT TOO THAT THE NEW -- IF THEY ARE PREGNANT FETUS IS EXPOSED TO THESE DRUGS. I WAS HORRIFIED WHEN I STARTED TO LOOK AT THE LITERATURE TO TRY TO IDENTIFY BECAUSE WE WERE SEEING THESE NUMBERS, THIS IS BASICALLY THE NUMBER OF NEONATAL INTENSIVE CARE UNIT ADMISSIONS NOR NEONATAL LAPSING PUBLISHED IN 2015 NEW ENGLAND JOURNAL THAT REPORTED CLOSE TO FIVE FOLD INCREASE IN UTILIZATION OF INTENSIVE CARE UNITS BY -- FROM NEONATAL LAPSE SYNDROME, SOME STATE WAS SIGNIFICANTLY HIGHER THAN THAT SO WE LOOKED AT THAT AND SAY WHY IS DRIVING VERY SIGNIFICANT INCREASE? PRESCRIPTION OPIOIDS. AND THOSE ARE THE NUMBERS. 17% OF PREGNANT WOMEN ARE PRESCRIBE AN OPIOID DURING PREGNANCY. THAT ACTUALLY IN TURN IS ASSOCIATED WITH A MORE SIGNIFICANTLY HIGHER RATE OF DOSE THOSE INDIVIDUALS LATER ON BECOMING CONTINUOUS TO USE OF OPIOID AND OF COURSE THAT INCREASES THE RISK OF THE NEWBORN COMING UP WITH WITHDRAWAL SYNDROME WHEN THEY ARE BORN. WHAT ARE THE THINGS WE CAN DO IN THAT RESEARCH SPACE? MANY THINGS ONE CAN DO. FOR EXAMPLE ONE OF THE LINES OF RESEARCH AND INQUERY THAT WE HAVE DOING IS IF YOU DO HAVE A FUND NEWBORN YOU CANNOT CONTROL WITH JUST BEHAVIORAL ENVIRONMENTAL INTERVENTIONS ARE THERE CERTAIN MEDICATIONS THAT CAN IMPROVE OUTCOME? AND THIS THIS IS A PAPER RECENT WILL I PUBLISHED SHOWING THAT INSTEAD OF MANAGING THE NEWBORN WITH MORPHINE WHICH IS CLASSICAL WAY OF DOING IT, YOU MANAGE THEM WITH BUPRENORPHINE, THAT'S SIGNIFICANTLY REDUCES THE NUMBER OF DAYS THEY HAVE WITHDRAWAL SYMPTOMS SO THE OUTCOMES AND COST SAVINGS ARE VERY LARGE. SIMILARLY, WE HAVE -- WE HAD FUNDED RESEARCH TO SHOW THAT WHEN YOU TREAT WOMEN WITH BUPRENORPHINE THAT ARE PREGNANT YOU SIGNIFICANTLY DECREASE LIKELIHOOD OF THEIR NEONATES ENDING UP IN UNIT COMPARED TO METHADONE. SO THIS IS AN AREA THAT IS RIPE FOR A LOT MORE INNOVATION AND MORE UNIQUE INTERVENTIONS. THIS IS A MEDICATION DEVELOPMENT RESEARCH AREA BUT THERE'S ALSO INCREDIBLE OPPORTUNITIES FOR PLEA AGREEMENTCATION RESEARCH OR BETTER PRACTICES, BETTER INSTRUMENTS TO PROPERLY RECORD AND GUIDE INTERVENTIONS FOR NEONATES BORN WITH ACUTE WITHDRAWAL. I WAS LYING TO YOU. THIS IS THE FINAL. THE FINAL IS WHOLE NIH EFFORT THAT HAS BEEN SPEARHEADED BY FRANCIS COLLINS TO TRY TO ACCELERATE DEVELOPMENT OF MEDICATIONS, THAT CAN HELP US DEAL WITH THE OPIOID CRISIS. AND THERE ARE TWO AREAS ONE DISCUSSING ON OPIOID USE DISORDER WHERE WE AS AN AGENCY HAVE BEEN PARTNERING WITH PHARMACEUTICAL INDUSTRY, MOST HAS BEEN SMALL COMPANIES, AND THE OPPORTUNITY NOW CREATING A PUBLIC PRIVATE PARTNERSHIP WHICH INTEREST MORE COMPANY, LARGE COMPANIES THAT NOT GONE INTO THIS SPACE ACTUALLY OFFERS UNIQUE ADVANTAGE IN TERMS OF SCIENTIFIC INFRASTRUCTURE AND RESOURCES. THIS PUBLIC PRIVATE PARTNERSHIP AIMS TO ACCELERATE DEVELOPMENT OF MEDICATION FOR OPIOID USE DISORDER OR PAIN, BY 50% AND IS DONE IN CLOSE COLLABORATION BETWEEN PHARMACEUTICAL INDUSTRY AND NIH BUT ALSO REGULATORY NOTE MOST NOTABLE THE FDA. SIX TOPOICS YOU SEE HERE, ONE DEVELOPING OF NEW FORMULATION OF COMBINATIONS OF MEDICATIONS. WHERE FOR EXAMPLE IT WOULD BE REMARKABLE TO HAVE A SIX MONTH INJECTABLE OR ANTAGONIST THAT COULD PROTECT PATIENTS THE MOST VULNERABLE PERIODS OF ADDICTION. MORE POTENT OR LONGER LASTING OPIOID ANTAGONISTS THAT CAN HELP ADDRESS THE PROBLEMS WE'RE FACING RIGHT NOW WITH FENTANYL. AS WELL AS MEDICATIONS THAT STIMULATE RESPIRATION THAT MAYBE ABLE TO HELP US REVERSE OVERDOSES IN DRUG COMBINATIONS. A THIRD ONE DOES NOT LOOK AS OBVIOUS AS THE OTHER IS THAT DEVELOPING VALIDATING ALTERNATIVE END POINTS. WHY? IN ADDITION THE OUTCOME, MAIN OUTCOME REQUIRED BY FDA ABSTINENCE. ABSTINENCE IS VERY, VERY DIFFICULT TARGET TO ACHIEVE. MEDICATIONS MAYBE DECREASE AM OF DRUG YOU USE, IN SO DOING DECREASE YOUR RISK FOR OVERDOSE MAYBE VALUABLE BUT DON'T REACH ABSTINENCE AND THEY ARE THEREFORE NOT WROUGHT TO NEXT STAGE. THOSE ARE THE AREAS OF PAIN, AREAS EMPHASIZED AND THIS HAS BEEN CHOSEN IN DIRECT DIALOGUE WITH PHARMACEUTICAL INDUSTRY. ONE IS A DATA SHARING COLLABORATIVE TO ALLOW US TO SHARE INFORMATION ABILITY FAILED TRY OUTS IN ANALGESIA AS WELL AS REPURPOSING OF ASSETS OF COMPOUNDS WHETHER FOR CLINICAL PURPOSES OR FOR RESEARCH. SECOND IS DEVELOP BIOMARKERS FOR PAIN, THIS HAS BEEN IDENTIFIED AS ONE OF THE MAIN ROADBLOCKS ON MEDICATION DEVELOPMENT WAY WE EVALUATE PAIN CELL REPORT FOR SUBJECTIVE SENSATION OF PAIN. FINALLY, THE DEVELOPMENT OF A CLINICAL TRIAL NETWORK TO FACILITATE AND ACCELERATE THE RATE AT WHICH PATIENTS CAN BE RECRUITED WHETHER COMMON CONDITION OR THOSE RARE PAIN CONDITIONS THAT FOR WHICH DEVELOPMENT OF ANALGESICS ARE HIGHLY BENEFICIAL. THIS WAS THE END OF THE LAST SLIDE, SO THEN EVERYTHING IS LIGHT AND CLEAR AFTER THIS. THANKS VERY MUCH FOR YOUR ATTENTION. [APPLAUSE] >> I THINK WE CAN TAKE ONE QUESTION BECAUSE WE'RE RUNNING BEHIND. KATHERINE. >> THANK YOU FOR A GREAT TALK. I CAN'T SEE YOU AND TALK IN THE MICROPHONE BUT JUST TO COMMENT, NOT TO MISS A VULNERABLE POPULATION, THANK YOU. LESSONS ON OPIOID OVERUSE IN TEENAGERS AND MANY TEENS AT RISK FOR PREGNANCY, IT'S A REAL PROBLEM FOR TEENAGE MOTHER. MANIABLE MIC >> THAT POPULATION HIGH RISK ARE THE GIRLS THAT ARE PREGNANT WE HAVE SEEN HIGHER RATES OF DRUG USE THAN IN THOSE NON-PREGNANT WHICH IS VERY DIFFERENT TO WHAT YOU SEE RATES ARE LOWER THAN GENERAL POPULATION. NOT AMONG ADOLESCENTS TEENAGERS THAT ARE PREGNANT SO NO RISKY BEHAVIOR, REALLY IMPORTANT TO DO TAILORED PREVENTION INTERVENTION IN THIS GROUP. >> ANOTHER SAMPLE THAT CHILDREN AD LESSENS ARE NOT SMALL ADULTS AND WE HAVE SEEN THAT IN CINCINNATI. NOT MANY REHABILITATION CENTERS FOR TEENAGERS EITHER SO WE MISS MARKETING TO THEM GETTING THE MESSAGE OUT AND THERE'S NOT AS MANY SERVICES. >> THE BRAIN IS DIFFERENT AND THAT'S WHERE OPPORTUNITIES TO UNDERSTANDING UNIQUENESS LEADS US TO BE MORE EFFECTIVE IN TERMS OF PREVENTION AND REMEDIATIONS. YOU DO HAVE HARMFUL EXPOSURE HOW DO YOU PROVIDE RESILIENCE TO THAT CASE. >> THANK YOU SO MUCH, NORA. WE LOOK FORWARD TO PARTNERING WITH YOU ON FANCY CLINICAL TRIALS AND NEONATAL OPIOID WITHDRAWAL SYNDROME, A B C D AND OTHER AREAS OF MUTUAL INTEREST. >> DIANA IS A FANTASTIC PARTNER THAT IMMEDIATELY EMBRACES THE IMPORTANCE OF DEVELOPING HUMAN BRAIN. I'M VERY GRATEFUL FOR THAT. THANKS A LOT. >> TURN THE MEETING OVER TO DR. HANN. >> OKAY. THANK YOU ALL FOR YOUR ATTENTION MOVING NOW TO THE CONCEPT REVIEW AND DOES CUSHION, PART OF THE MEETING, WE HAVE SEVEN CONCEPTS TO DISCUSS WITH YOU TODAY. FOR EACH I'LL ASK STAFF JOIN AT THE TABLE AND PROVIDE A BRIEF OVERVIEW OF THE INITIATIVE AND ASK COUNCIL FOR ANY DISCUSSION REGARDING CONCEPT AT THE CONCLUSION OF DISCUSSION OF EACH I WILL ASK COUNCIL MEMBERS WHETHER THEY CONCUR OR NOT. IF I COULD ASK STAFF, FIRST IS ERIC LORENZO, IF YOU CAN SIT DOWN NEXT TO MELISSA. THAT WILL BE GREAT. HE WILL PRESENT THE FIRST ARCHIVED DATA TO ADVANCE MATERNAL PEDIATRIC HIV AIDS RESEARCH. >> GOOD MORNING, AN IMPORTANT GOAL OF OUR INSTITUTE IS TO MAXIMIZE RESEARCH RESOURCES AND TOOLS TO MATERNAL PEDIATRIC INFECTIOUS DISEASE BRANCH, ASK APPROVE NOR TITLE USING NICHD ARCHIVE DATA, SPECIMEN COLLECTIONS TO ADVANCE MATERNAL AND PEDIATRIC HIV RESEARCH. THE PURPOSE OF-FUNDING OPPORTUNITY ANNOUNCEMENT IS TO ADDRESS THE NEEDS OF THE MATERNAL SCIENTIFIC COMMUNITY FOR RESEARCH, DATA TRANSLATION AND SHARING. THIS INITIATIVE ENCOURAGES AND DATA IN THE NICHD REPOSITORY THE ANSWER NEW RESEARCH QUESTIONS RELATED TO PSYCHOMISSION AND PRIORITIES. SPECIFICALLY THIS ANYBODITIVE FOR SECONDARY ANALYSIS TO MAXIMIZE HIV AIDS STUDY DATA AND SPECIMENS. THIS WILL ASK NEW DATA ARRIVEDED FROM ANALYSIS PERFORMED TO BE RETURNED TO THE NICHD DATA AND SPECIMEN HUB DASH TO CONTINUE ADVANCEMENTS IN ANALYSIS TRANSLATION AND DECEMBER SIMILAR NATION OF RESEARCH FINDINGS. TRANSLATION OLE THESE HIV AIDS DATA TO RESEARCH FINDINGS IS CRITICAL TO ADVANCING MATERNAL AND CHILD HEALTH. >> COUNCIL MEMBER DISCUSSION. ALL RIGHT. ALL THOSE THAT CONCUR WITH THIS CONCEPT MOVING FORWARD. THOSE NOT IN FAVOR? ABSTENTIONS. DR. KOPF AND BUTTE, THUMBS UP, GREAT. THANK YOU VERY MUCH. THANK YOU, ERIC. NEXT WE'LL HAVE DR. DAN JOHNSTON JOIN US. HE WILL BE PRESENTING THE FIRST OF TWO CONCEPTS. THE FIRST IS A PRESENTATION ON THE DEVELOPMENT OF NOVEL NON-STEROIDAL CONTRACEPTIVE METHODS. >> PROGRAM SEEKS COUNCIL APPROVAL FOR NOVEL NON-STEROIDAL CONTRACEPTIVE METHODS THERE'S A NEED FOR MODES OF CONTRACEPTIVES MEN AND WOMEN AND THIS ANYBODITIVE CONTINUES A PARADIGM SHIFT TOWARDS MORE SPECIFIC CONTRACEPTIVE MODAL I THES THAT DON'T ACT BY CLASSIC STEROIDAL MECHANISMS. THAT FOCUSED ON MALE OR FEMALE NON-STEROIDAL MECHANISMS THE REQUESTED RFA SIGNIFICANTLY EXPANDS THE SCOPE TO ALLOW BOTH MALE AND FEMALE METHOD DEVELOPMENT AS WELL AS DEVELOPMENT OF DELIVERY DEVICES AND MULTI-PURPOSE PREVENTION TECHNOLOGIES. THE NICHD IS THE PRIMARY FUNDER OF EARLY STAGE CONTRACEPTIVE RESEARCH THROUGHOUT THE WORLDND CONTINUED FUNDING IS PARAMOUNT IMPORTANCE TO THE FIELD. THE PROPOSED CONCEPT ALIGNED WITH BRANCH PRIORITIES AND THE NICHD VISIONING MANDATE TO IDENTIFY NOVEL MOLECULAR TARGETS TO DEVELOP NEW CONTRACEPTIVE METHODS. THANK YOU. >> THANK YOU, DAN. >> I HAVE A QUESTION. >> THIS IS GREG KOPF WILL THE WORK ON THE (INAUDIBLE) BE COORDINATED IN ANY WAY WITH THE ACTIVITY OF NIAID? >> YES, I EXPECT WE ARE DISCUSSION IT WITH NIAID AT THIS TIME, ALSO BEING DISCUSSED WITH OUR OWN INTERNAL GROUP THAT WORKS IN THE AREA. >> THANK YOU. >> ANY FURTHER DISCUSSION? THOSE THAT CONCUR? THOSE THAT DO NOT. THANK YOU. DAN MOVE ON TO SECOND ONE? >> SURE. PROGRAM SEEKS COUNCIL APPROVAL FOR SUPPORTING CHEMICAL STREAMING OPTIMIZATION FACILITY. THERE'S TREMENDOUS NEED FOR ALTERNATIVE MODES OF CONTRACEPTION FOR MEN AN WOMEN AND THE CRB SUPPORTS BAY SUCK RESEARCH THAT IDENTIFIES PROMISING NEW CONTRACEPTIVE TARGETS. THIS INITIATIVE CONTINUES THE SUPPORT OF EFFORTS TO DEVELOP NOVEL MOLECULES THAT ACT ON VALIDATED TARGETS. INITIATIVE WILL PROVIDE NECESSARY RESOURCES TO MERITORIOUS INVESTIGATORS TO ENABLE SMALL MOLECULE DISCOVERY AND OPTIMIZATION THROUGH ASSAY DEVELOPMENT, MEDICINAL CHEMISTRY, STRUCTURAL BIOLOGY AND BIOLOGICAL TESTING. THE NICHD IS THE PRIMARY FUNDER OF EARLY STAGE CONTRACEPTIVE DEVELOPMENT THROUGHOUT THE WORLD AND CONTINUED FUNDING IN ADDITION AREA IS PARAMOUNT IMPORTANCE TO FIELD BRANCH PRIORITIES AN VISIONING MANDATE TO IDENTIFY NOVEL TARGETS TO DEVELOP NEW CONTRACEPTIVE MODES. >> THANK YOU. COUNCIL DISCUSSION. >> HOPE YOU CAN HEAR ME. I'M ASKING THAT THIS BE WITH OTHER RFAS IN THE PAST WHEN APPROPRIATE STATE WILL BE MADE OPEN ACCESS THROUGH PUB CHEM OR OTHER APPROPRIATE REPOSITORIES. FOR SCREENING DATA. >> GREAT SUGGESTION. THANK YOU. ANY FURTHER COUNCIL DISCUSSION? THOSE THAT CONCUR? THOSE THAT DO NOT? THANK YOU, DAN. NEXT IF I CAN ASK DR. BOB TAMBORO TO JOIN US. HE WILL BE PRESENTING ON THE PEDIATRIC CRITICAL CARE AND TRAUMA SCIENTIST DEVELOPMENT PROGRAM. >> >> PROGRAM SEEKS COUNCIL APPROVAL FOR INITIATIVE ENTITLED PEDIATRIC CRITICAL CARE AND DEVELOPMENT PROGRAM A NATIONAL TRAINING PROGRAM TO DEVELOP SUCCESSFUL PEDIATRIC CRITICAL CARE AND TRAUMA PHYSICIAN SCIENTISTS. IT WILL FACILITATE IDENTIFICATION AND TRAINING OF EARLY CAREER SCHOLARS FROM ACROSS THE COUNTRY TO CONDUCT RESEARCH ON KNOWLEDGE GAPS THAT EXIST IN UNDERSTANDING AND TREAT OF CRITICAL ILLNESS AND INJURY IN CHILDREN. SINCE ITS INCEPTION, THE PROGRAM HAS SUCCESSFULLY TREATED 44 JUNIOR FACULTY -- TRAINED THEM FROM ACROSS THE UNITED STATES. VAST MAJORITY OF THESE INDIVIDUALS HAVE SUBSEQUENTLY BEEN AWARDED FEDERAL FUNDING FOR RESEARCH. DESPITE THESE SUCCESSES AND GIVEN CLINICAL AND PHYSICAL DEMANDS OF CRITICAL CARE, TRAUMA TRAINING THE PAUCITY OF ESTABLISHED RESEARCH MENTORS IN THESE FIELDS AND FINANCIAL INCENTIVE OF PURE CLINICAL PRACTICE. A NATIONAL RESEARCH TRAINING INFRASTRUCTURE IS NEEDED TO MAINTAIN A WORK FORCE WELL PREPARED PHYSICIAN SCIENTISTS. WITHOUT SUPPORT OF NATIONAL PROGRAM THE SYNERGY SPAWNED BY THE PROGRAM THAT'S FUELED RESEARCH IN CRITICAL AND TRAUMA CARE WILL BE LOST. THUS, THE OVERARCHING OBJECTIVE OF THIS INITIATIVE IS TO IDENTIFY STIMULATE AND TRAIN EARLY CAREER INVESTIGATORS TO CONDUCT RESEARCH THAT WILL IMPROVE OUTCOMES AMONG CRITICALLY ILL AND INJURED CHILDREN BY ENHANCING RESEARCH CAPACITY AND INFRASTRUCTURE IN THE FIELD ON AN NATIONAL LEVEL. THE CONCEPT ALIGNS WITH NICHD VISION AREAS OF HEALTH AND DISEASE IN CONDUCT OF SCIENCE AND WITH ALL PEDIATRIC TRAUMA AND CRITICAL ILLNESS BRANCH PRY YOUR I IT IS NOTABLY WITH CARE AND TREATMENT OF TRAUMA AND CRITICAL ILLNESS FOR PEDIATRIC POPULATIONS. >> COUNCIL DISCUSSION. >> SOME BOB, IS THIS A K 12 PROGRAM? WHAT IS THIS? (OFF MIC) >> JUST PER DIANA OR CATHY'S ARTICLE HOW SUCCESSFUL IS THIS THE GRADUATES OF THIS PROGRAM AND SHOULD WE PUT MONEY INTO THIS VERSUS INDIVIDUAL CASE? >> FIT OOHs A GREAT FAIR QUESTION. I DON'T THINK THE TWO PROGRAMS OR THE TWO PHILOSOPHIES ARE MUTUALLY EXCLUSIVE. FIELDS OF PEDIATRIC TRAUMA CARE ARE STILL RELATIVELY YOUNG AND I DON'T THINK WE HAVE THE RESEARCH MENTORS THROUGHOUT THE COUNTRY. WE HAVE A FEW SITES WHERE I THINK PEOPLE CAN GO AND ARE GOING AND DOING WELL WITH INDIVIDUAL Ks BUT IF WE ENHANCE PEDIATRIC CLINICAL CARE RESEARCH ACROSS THE COUNTRY WE NEED GOOD MENTORS, GOOD INVESTIGATORS THROUGHOUT THE COUNTRY AND NOT JUST A FEW SITES SO AT THIS POINT IN TIME WE STILL NEED THIS PROGRAM. AS WE EVOLVE AND GROW AS SPECIALTY WE'RE GOING TO FALL IN WITH THE NICHD PLAN TRANSITIONING K-12 FOR INDIVIDUAL K AWARDS. >> HOW SUCCESSFUL HAS THE 44 PEOPLE BEEN IN TERMS OF GETTING INDIVIDUAL RESEARCH GRANTS? >> IN THE FIRST TWO CYCLES 75 AND 80% RECEIVED THE SUBSEQUENT K AWARD AND THE FIRST CYCLE WHICH IS THE ONLY ONE FAIRLY TO ASSESS OVER 40% RECEIVED R AWARD SO I THINK IT'S BEEN INCREDIBLY SUCCESSFUL AND IF YOU COMPARE WITH NATIONAL NUMBERS, THEY'RE TWICE AS SUCCESSFUL AS OTHER APPLICANTS. >> THANK YOU. >> ANY FURTHER DISCUSSION FROM COUNCIL? THOSE THAT CONCUR? THIS CONCEPT MOVING FORWARD? THOSE THAT DO NOT OKAY. THANK YOU. THANK YOU, BOB. NEXT DR. LOU DEPAUL OBJECTION -- DEPAULO WILL PRESENT ON CLINICAL SITES AND DATA COORDINATING CENTER. >> GOOD MORNING. PROGRAM SEEKS COUNCIL APPROVAL FOR INITIATIVE TITLED GROUP MEDICINE NETWORK CLINICAL SITES AND DATA COORDINATING CENTER. IN FERTILITY DEFINED AS INABILITY TO CONCEIVE WITHIN ONE YEAR OF PROTECTED INTERCOURSE AFFECTS 80 MILLION INDIVIDUALS WORLDWIDE OR 10 TO 15% REPRODUCTIVE AGE COUPLINGS. TO THIS END THE REPRODUCTIVE MEDICINE NETWORK WAS ESTABLISHED IN 1989 ADS A MEANS FOR THE NICHD TO SUPPORT CLINICAL TRIALS THAT ADDRESS INFERTILITY. THE MOST RECENT COMPETITION OF THE RMN IN 2013 SIX AWARDS FOR CLINICAL SITES AND ONE AWARD FOR DATA COORDINATING CENTER WERE FUNDED. THAT AND RESULTED IN THE CONDUCT OF THREE TRIALS ADDRESS MANAGEMENT OF NORMAL PREGNANCY, AFFECTS OF LIFESTYLE MODIFICATION ON INFERTILITY IN BEES WOMEN AND AFFECTS OF ANTIOXIDANT TREATMENT ON MALE INFERTILITY. THE OBJECTIVE OF THIS INITIATIVE IS TO SUPPORT A MULTI-CENTER CLINICAL TRIAL WITH THE GOAL OF DEVELOPING MORE EFFECTIVE DIAGNOSTIC TREATMENT AND PREVENTION STRATEGIES FOR INFERTILITY. THE CONCEPT ALIGNS WITH THE NICHD VISIONARY REPRODUCTION AND ALSO HIGH PROGRAM PRIORITY AREAS OF THE BRANCH BUT IN PARTICULAR EARLY PREGNANCY LOSS GENETIC BASIS OF IDIOPATHIC INFERTILITY AND METABOLISM NUTRITION AND REPRODUCTION. >> THANK YOU, LOU. COUNCIL DISCUSSION? >> I HAVE A COMMENT, A QUESTION. GREG KOPF. GIVEN THE FACT THERE'S ALSO A CONTRACEPTIVE CLINICAL TRIAL NETWORK AND FERTILITY AND INFERTILITY CAN BE REGARDED AS OPPOSITE ENDS OF THE SAME COIN AND CONTRACEPTION VIEWED DO YOU SEE THESE TWO NETWORKS COULD FUNCTION IN TERMS OF EXCHANGING INFORMATION OR LEARN FROM ONE ANOTHER IN TERMS OF OUTCOMES OF THEIR TRIALS? >> WE CAN ALWAYS EXCHANGE INFORMATION AND LEARN FROM EACH OTHER'S TRIALS BUT I THINK YOU HAVE TWO SEPARATE ISSUES TO DEAL WITH, ONE INFER UNTIL POPULATION THAT REQUIRES NEW DIAGNOSTICS AND TREATMENT STRATEGIES AND ANOTHER REQUIRES NEW APPROACHES TO CONTRACEPTIVE DEVELOPMENT. >> ANY FURTHER DISCUSSION? >> MOST PEOPLE ARE GOING TO GUESS WHAT I'M GOING TO SAY. I THINK -- I (INDISCERNIBLE) NICHD TWO OUT OF THE SEVEN CONCEPT CLEARANCES STRANGEICALLY, IT'S MISSING IN THIS ONE. I WENT TO THE EXISTING -- AND I COULDN'T FIND EASY WAY DOWNLOAD EXIST ORGANIZE COMPLETED TRIALS DATA KEEPING CONSISTENT WITH THE OPEN DIRECTION FOR NICHD, REALLY WOULD ASK THAT DASH IS REALLY REQUIRED FOR ANY NOVEL RECIPIENT OR EXISTING RECIPIENT FOR THE COORDINATING CENTER. >> WE JUST HAD OUR FIRST DATA DUMP FOR ONE OF OUR TRIALS INTO DASH COUPLE OF WEEKS AGO. >> STRANGELY ENOUGH FROM RMN AT THIS POINT PUBLICLY AVAILABLE. >> DULY NOTED. THANK YOU. ADDITIONAL DISCUSSION? THOSE THAT CONCUR WITH CONCEPT MOVING FORWARD? THOSE THAT DO NOT. THANK YOU, LOU. MELISSA. OKAY. NEXT ASKING DR. PARISI JOIN US FOR THE LAST TWO CONCEPTS. FIRST BEING INTELLECTUAL AND DEVELOPMENTAL DISABILITIES RESEARCH CENTERS. >> PROGRAM SEEKS COUNCIL APPROVAL FOR INITIATIVE ENTITLED INTELLECTUAL DISABILITIES RESEARCH CENTERS IDRR 2019 THEY SERVE, SERVE AS CATALYST FOR RESEARCH TRAINING ACROSS THE INSTITUTED AS YOU HEARD THIS MORNING. THE IDDRC EVOLVED SINCE INCEPTION IN 1960 INTO A NETWORK OF COLLABORATIVE CENTER CREATING SHARED RESOURCES AND PROJECT INVENTORY AND ESTABLISHING STANDARDS FROM MODEL ORGANISM TESTING AND EVALUATION. THERE'S A CONTINUED NEED FOR CUTTING ONLY APPROACHES TO OMIC ANALYSES, MANIPULATION, AND COMPLEX COGNITIVE AND BEHAVIORAL PHENOTYPING THAT LEAD TO NOVEL THERAPIES FOR IDD CONDITIONS. GOAL TO SUPPORT INTEGRATED RESEARCH CENTERS TO PROVIDE CORE EQUIPMENT RESEARCH INFRASTRUCTURE AND PERSONNEL FOR INVESTIGATORS TO UNDERSTAND THE CAUSES OF AND DEVELOP TREATMENTS FOR IDDs. THIS NEW CYCLE THENT CENTERS PROGRAM WILL PROVIDE IMPLEMENTATION TO BETTER TO OTHER INVESTIGATORS WITH IDD CONDITIONS AND PUBLIC AT LARGE. THIS INITIATIVE ALIGNS WITH NICHD VISION STATEMENTS RELATED TO UNDERSTANDING THE UNDERPINNINGS OF IDD, NEUROLOGICAL BASES OF COGNITIVE DISORDERS INCLUDING OFFTISM AND DEVELOPMENT OF EFFECTIVE INTERVENTIONS FOR THESE CONDITIONS. THANK YOU. >> THANK YOU, MELISSA. DISCUSSION FROM COUNCIL? THOSE THAT CONCUR GOING FORWARD? THOSE NOT IN FAVOR? THANK YOU GUYS WITH THUMBS UP APPRECIATE THAT. THE FINAL CONCEPT. >> PROGRAM SEEKS COUNCIL APPROVE FOR INITIATIVE TITLED NEWBORN SCREENING TRANSLATIONAL RESEARCH NETWORK NBS TRN 2018, FOR NEWBORN SCREENING ACROSS NIH. NEWBORN SCREENING PROGRAMS SCREEN 4 MILLION INFANTS PER YEAR TO IDENTIFY THOSE AT RISK FOR CONGENITAL DISORDERS WITH RECOGNITION EARLY INTERVENTIONS REDUCE MORBIDITY AND MORTALITY. THE GOAL OF THE NBS TRN IS FACILITATE RESEARCH THROUGH ASSISTANCE AND ACCESSING DRIED BLOOD SPOTS AVAILABLE THROUGH STATE SCREENING PROGRAMS AND ENABLE DATA COLLECTION ANALYSIS AND SHARING OF NEW TECHNOLOGIES AND TREATMENTS FOR NEWBORN SCREENING CONDITON, SUPPORT EXPLORATION OF ETHICAL LEGAL AND SOCIAL IMPLICATIONS OF NEWBORN SCREENING AND FOSTER COMMUNITY OF COLLABORATIVE RESEARCH ON NEW NEWBORN SCREENING CONDITIONS. THIS RESEARCH INFORMS THE EVIDENCE REVIEW THAT EVALUATES NOMINATIONS FOR CONDITIONS TO BE ADDED TO THE RECOMMENDED NEWBORN SCREENING PANEL. THE NBSTRN IS RESOURCE FOCUSED ON FOUR MAIN INFORMATION TECHNOLOGY SOLUTIONS THAT SUPPORT COLLECTION UTILIZATION AND SHARING OF MATERIALS AN INFORMATION FOR NEWBORN SCREENING RESEARCH. THESE INCLUDE A VIRTUAL REPOSITORY OF DRIED BLOOD SPOTS, LABORATORY PERFORMANCE DATABASE USED BY ALL STATE NEWBORN SCREENING LABS IN THE UNITED STATES, A LONGITUDINAL PEDIATRIC DATA RESOURCE AND DATA WAREHOUSE, AND LC ADVANTAGE RESOURCE FOR NEWBORN SCREEN RESEARCHERS ON ISSUE. THE NEW CYCLE WILL CONTINUE DEVELOPMENT WITH PRIORITIZATION OF DATA COLLECTION HARMONIZATION FOR SECONDARY PURPOSES. ALIGNS WITH NICHD VISION STATEMENTS RELATED TO EARLY RECOGNITION OF FETAL BRAIN AND OTHER DEFECTS AND BRANCH PRIORITIES ON RESEARCH NEWBORN SCREENING TESTS CONDITIONS AND TREATMENTS. THANK YOU. >> THANK YOU, MELISSA. COUNCIL DISCUSSION. >> JUST LIKE THE OTHER, I TO US THE TITLE WAS ONE THING BUT THERE'S CREATION OF DATABASES VIRTUAL OR NOT AND WHERE APPROPRIATE, SHOULD BE SUN CROW RECOGNIZED WITH DASH. WOULD BE GREAT TO HAVE A SINGLE POINT OF ENTRY FOR OPEN ACCESS DATA CREATED OR FUNDED BY NICHD AND IT WOULD BE TRAGIC TO ADD MORE SEPARATE REPOSITORIES BEING CREATED. SOP ANYTHING WE CAN DO TO TRY TO GET DASH TO BE SINGLE POINT WOULD BE GREAT. >> THANK YOU FOR THAT COMMENT AND IN FACT, I THINK THAT THERE ARE OPPORTUNITIES FOR SYNERGY BETWEEN THE RESOURCES AND I WILL LIKE TO HAVE CONVERSATIONS WITH LEADERSHIP AT NICHD AROUND THOSISH ISSUES. >> GREAT. THANK YOU. ANY ADDITIONAL DISCUSSION? ALL RIGHT. THOSE THAT ARE IN CONCURRENCE WITH THIS MOVING FORWARD? THOSE WHO ARE NOT? ALL RIGHT. THANK YOU. THANK YOU, MELISSA. >> NOW THAT WE HAVE EXHAUST ACTIVELY LOOKED AT THESE SEVEN, I WOULD LOVE TO KNOW WHAT NUMBERS 48 THROUGH 20 WERE ON THE CONCEPT LIST OR WHAT THE PROCESS IS TO COME UP WITH THESE SEVEN. ARE THERE CONCEPTS THAT DIDN'T MAKE IT HERE? >> GOOD QUESTION. WHAT ARE YOU ARE SEEING ARE PROCEEDS OF A THOROUGH PLANNING PROCESS THAT WE WORK WITH TWICE A YEAR. LARGEST IN UM IS MARITIME THE PLAN INITIATIVES AND WE PLAN THEM A YEAR AND A HALF IN ADVANCE. SO WHAT IS PRESENTED TO YOU NOW WAS PRESENTED -- WENT THROUGH OUR INTERNAL PLANNING PROCESSES A WHILE AGO. WE DO THAT BECAUSE OF LENGTH OF TIME TO CREATE THE FOAs, ET CETERA SO WE STOP HERE BEFORE WE CREATE THE FOAs AND SOLICITATIONS ARE CREATED AFTER THAT. SO THAT IN TERMS OF NUMBERS OF I WOULD HAVE TO LOOK, ESSENTIALLY TO SEE HOW MUCH WE WEPT THROUGH. WE BRING THEM TO YOU, THE PROCEEDS FROM THE PLANNING PROCESS ARE DISTRIBUTED THROUGHOUT YOUR COUNSEL MEETINGS. SO WE HAD A SMALL BATCH IN OCTOBER, LARGER BATCH NOW AND ANOTHER BATCH WE BROUGHT IN JUNE AND THEN IT H START OVER AGAIN. WE DISTRIBUTE THEM IN ORDER TO DO SEQUENCING WITH PEER REVIEW. SO THAT'S HOW THAT HAPPENS SO THEY EMANATE FROM THAT PROCESS, IN TERMS OF NUMBERS, IT VARIES DEPENDING ON WHAT IS CYCLING OFF IN TERMS OF AVAILABILITY OF OUR FUNDS AS WELL AS WHETHER WE WISH TO PUT FUNDS ON THEM OR HAVE THEM BE GENERAL OPEN ACCESS IF YOU WILL FOAs THAT DON'T HAVE A SET ASIDE. SO THERE'S SEVERAL NUMBERS OF FACTORS, HAPPY TO AT THIS DOES THAT WITH YOU -- DISCUSS WITH YOU IN MORE LENGTH. >> ALWAYS INTERESTED IN WHO DOESN'T MAKE IT. >> THANK YOU, DR. HANN. NOW I WOULD LIKE TO TAKE THE OPPORTUNITY, IT'S A BITTERSWEET OPPORTUNITY BUT HEART FELT TO THANK OUR SIX RETIRING COUNCIL MEMBERS. DR.S FLYNN, KOPF, SAADE ZIMMET AND DR. SHIELDS. THANK YOU FOR YOUR CONTRIBUTIONS TO THE NICHD ADVISORY COUNCIL AND ESPECIALLY THOSE WHO GRACIOUSLY AGREED TO EXTEND YOUR TENURE FOR THIS MEETING DUE TO SOME OF THE ISSUES WE HAVE IN TERMS OF GETTING OUR NEXT GROUP APPROVED. OFFICER ACTIVE KATES AND LETTERS OF APPRECIATION AND I WANT TO POINT OUT THAT NORMALLY THESE ARE SIGNED BY THE SECRETARY OF HEALTH AND HUMAN SERVICES. BUT SINCE WE DON'T HAVE A SECRETARY OF HEALTH AND HUMAN SERVICES YOUR CERTIFICATES ARE SIGNED BY DR. COLLINS WHICH MAKES THEM ESPECIALLY COLLECTIBLE. SO I'M GOING TO CALL EACH OF YOUR NAMES AND I WOULD APPRECIATE IT IF EACH OF YOU WOULD PROVIDE US WITH SOME BRIEF COMMENTS ON YOUR TENURE AS MEMBER OF THE COUNCIL. THIS IS YOUR EXIT INTERVIEW. WE'LL START WITH DR. FLYNN. >> IT IS TRULY BEEN MY HONOR AND PRIVILEGE TO SERVE ON THE COUNCIL. I THINK WORKING ONE'S WAY UP THROUGH THE COMPLEXITIES OF NIH FUNDING AND YOU CONTINUALLY LEARN SO THIS HAS BEEN THE ICING ON THE CAKE TO SEE WHAT HAPPENS BEYOND NOT ONLY WHEN YOU SUBMIT SOMETHING THEN TO REVIEW PROCESS AND THEN TO SORT OF THE OVERREVIEW PROCESS. IT SPEAKS WELL TO THE TRANSPARENCY OF THE PROCESS. I CAN'T SAY DURING TIME I SPENT TIME ON COUNCIL I HAVE GOTTEN MY WAY AND MY GRANTS HAVE BEEN FUNDED. NONETHELESS, I THINK THE TRANSPARENCY IS PARTICULARLY IMPRESSIVE AS THE QUALIFICATIONS OF PEOPLE WORKING IN NICHD AND OTHER COUNCIL MEMBERS SO THANKS EVEN AGAIN, IT'S BEEN A PLEASURE AND I WISH YOU GREAT FORTUNE, WONDERFUL THINGS ON THE HORIZON, I'M CONFIDENT YOU WILL ACHIEVE THEM ALL. >> THANK YOU SO MUCH. FOR YOUR SERVICE. DR. KOPF. >> YES. THANK YOU. I WOULD LIKE TO ECHO DR. FLYNN'S COMMENTS FOR SAKE OF BREVITY BECAUSE I KNOW WE'RE HOLDING YOU UP FROM LUNCH BUT AGAIN TO THANK ALL OF YOU FOR THE OPPORTUNITY TO SERVE ON THE COUNCIL, IT'S BEEN A REAL PRIVILEGE TO GET TO KNOW THE OTHER MEMBERS DURING MY TENURE AS WELL AS WORKING WITH OUTSTANDING LEADER SHIP OF THE NICHD. I HAVE TO GIVE SHOUT OUT TO THE PROGRAM STAFF FOR OVER THE YEARS AND THANK THEM FOR THEIR COMMITMENT AND HARD WORK, IT TRULY IS TERRIFIC TO WATCH. ONE OF THE THINGS THAT REALLY STRUCK ME AFTER SERVING IS THE NUMBER AND VARIETY OF INITIATIVES YOU HAVE ONGOING AT NICHD MANY WHICH I WAS NOT AWARE BEFORE I CAME ON COUNCIL. THE WORK YOU DO HAS SUCH IMPACT AND AS SHOWN BY THE PRESENTATIONS TODAY, ESPECIALLY PRESENTATION BY THE EGAN FAMILY I THINK THIS TYPE OF OUTPUT AND PRESENTATIONS HELPS TO NICHD TO HELP DEFINE STRATEGY AND REALLY SINCE WE TALKED EARLIER TODAY ABOUT IMPACT REALLY CAN FOCUS ON THE IMPACT ON WHAT YOU DO. SO AGAIN, I WISH Y'ALL THE BEST OF LUCK AND I KNOW THAT THE NICHD IS IN GREAT HANDS. THANK YOU. >> THANK YOU SO MUCH, GREG FOR YOUR COMMENTS. I REALIZE THAT ANOTHER ASPECT OF SAYING GOODBYE TO EVERYBODY IS THIS IS THE GROUP I SERVED ON COUNCIL WITH SO I HAVE SPECIAL RELATIONSHIP WITH THIS GROUP. DR. PETRILL. >> DIANE, I DON'T KNOW IF YOU REMEMBER YOU WERE MY SENIOR COUNCIL BUT DISO YOU MIGRATE DOWN THE TABLE NOTICE WE'RE SITTING HERE, THIS IS THE DRAIN AS WE GO OUT. SO YOU'RE SITTING NEXT TO ME AT FIRST COUNSEL SO I JUST WANT TO REITERATE WHAT EVERYONE ELSE SAID, THANK YOU, HONOR TO SERVE BE MY COLLEAGUES ON COUNCIL BUT