I WOULD LIKE TO OPEN UP THIS INCLUSION ACROSS THE LIFE SPAN WORKSHOP. I AM MARIE BERNARD DEPUTY DIRECTOR OF NIA AND CO CHAIR OF THE INCLUSION GOVERNMENT'S COMMITTEE THAT HAS HAD OVERALL RESPONSIBILITY OF ADDRESSING THESE ISSUES. DR. CLAYTON WHO YOU WILL HEAR FROM LATER THIS MORNING IS THE OTHER CO CHAIR OF THIS COMMITTEE AND WE'RE REALLY PLEASED TO SEE YOU HERE. MY JOB WAS SIMPLY TO MAKE SURE YOU KNEW THE LOGISTICS FOR TODAY, NUMBER ONE WHERE THE PATH ROOMS ARE TO THE RIGHT AND LEFT AS YOU GO OUT OF THE ROOM. AND NUMBER TWO, WE'RE NOT GOING TO DO FORMAL INTRODUCTIONS OF EACH OF THE SPEAKERS, WE WILL JUST FLOW THROUGH TO MAKE SURE WE MEET OUR TIME GOALS. SO WE'RE GOING TO HAVE OPENING REMARKS FROM NIH LEADERSHIP, INCLUDING DR. RICHARD HOTUS, DIRECTOR OF THE NATIONZAL INSTITUTE ON AGING, DR. DIANEA BIANCI, WITH THE NCHD, AND WE WILL HAVE A PRESENTATION FROM DR. BURGOIS, AND A PRESENTATION FROM DR. CLAYTON,A--A PRESENTATION FROM CL PERSTIVAS, AND THEAN YOU WILL GET REAL ORDERS FROM THIS WORKSHOP. MOST IMPORTANTLY WE HAVE DR. FRANCIS COLLINS THE NIH DIRECTOR HERE TO SET THE STAGE AND TO GIVE YOU YOUR CHARGE SO I WILL TURN IT OVER TO DR. COLLINS AND IT WILL FLOW FROM THERE. >> WELL, THANKS MARIE AND HELLO TO ALL OF YOU. THANK YOU FOR BEING HERE FOR THE NEXT 25 HOURS. WHERE WE'RE COUNTING ON THIS GROUP TO PROVIDE REALLY SIGNIFICANT INPUT IN THE VERY IMPORTANT AREA THAT HAS BEEN SOMETHING NIH HAS BEEN INTERESTED IN EXPLORING NOW FOR FOUR YEARS BUT IT'S SORT OF COMING TOGETHER NOW IN A WAY THAT I'M HOPING WE WILL LEARN A LOT FROM YOU ABOUT XABLGHTLY WHAT KIND OF--EXACTLY WHAT KIND OF ACTIONS WE MIGHT THINK ABOUT TAKING. THIS NOTION OF INCLUSIO ACROSS THE LIFE SPAN WHICH I THINK IS ORCHESTRATED BY THE ART WORK, I DON'T KNOW WHO WE GET FOR THAT, BUT IT GETS YOU IN THE RIGHT-- >> [INDISCERNIBLE] >> WELL DONE NIA STAFF MEMBER. IT KIND OF HELPS US IMMEDIATELY GET INTO THE MIND SET OF WHY WE ARE REALLY HERE BECAUSE WE ARE AFTERALL ENTERED--INTERESTED IN THE HEALTH OF ALL PEOPLES THAT INCLUDES PEOPLE OF DIFFERENT BACKGROUNDS, ETHNICITIES, SOCIOECONOMIC STATUS AND ALSO DIFFERENT PARTS OF THE LIFE SPAN, A LIFE SPAN WE HOPE WILL BE A HEALTH SPAN FOR PEOPLE AS MUCH AS WE CAN ARRANGE IT AND YET WE ARE AWARE THAT THE WAY IN WHICH WE DO CLINICAL STUDIES DOESN'T ALWAYS OPTIMIZE THAT KIND OF INCLUSIVENESS. AND THAT'S WHAT WE'RE HERE, REALLY TO TALK ABOUT FOR THESE 25 HOURS AND TO TRY TO UNDERSTAND WHAT STEPS WE MIGHT TAKE. THIS--AS I SAID IS NOT A NEW IDEA FOR NIH TO BE CONSIDERING GOING BACK TO 2013. THE IGC, THAT IS THE INCLUSION GOVERNANCE COMMITTEE STARTED EXAMINING WHETHER WE WERE DOING THE RIGHT THING ABOUT INIVENESS OF CHILDREN AND AS YOU KNOW WE TOOK STEPS TO CHANGE THE DEFINITION OF CHILDREN FROM ZERO-21, DOWN TO ZERO-18 AND THEN DISCUSSIONS IN 2015 ABOUT OLDER ADULTS AS WE LOOKED AT OUR CLINICAL STUDIES AND REALIZED THAT IN FACT MANY OF OUR STUDIES THAT MIGHT APPROPRIATELY HAVE LOOKED AT THE ELDERLY TENDED TO LOOK AT YOUNGER INDIVIDUALS THAN THAT DEMOGRAPHIC WOULD REPRESENT. SO ALL OF THOSE PARTICULAR DISCUSSIONS LED US TO THE CONCLUSION WE NEEDED TO DO SOMETHING IN THIS SPACE. AND THEN WE GOT ANOTHER INCENTIVE WHICH IS THE 21st CENTURY CURES ACT, SOMETHING WE WERE DEEPLY INVOLVED IN PROVIDING INFORMATION ABOUT TOLET MEMBERS OF CONGRESS WHO OVER THE COURSE OF TWO YEARS SHAPED WHAT IS CALLED THE MOST SIGNIFICANT PIECE OF LEGISLATION EFFECTING NIH IN QUITE A LONG NUMBER OF YEARS ALTHOUGH 21st CENTURY CURES AWLTS HAS A HEAVY FOCUS ON FDA. YOU MAY REMEMBER THAT WHEN THIS PAST, BOTH HOUSES OF CONGRESS WAS SIGNED INTO LAW BACK IN DECEMBER, DURING THE LAME DUCK SESSION, THERE WAS A LOT OF CHEERINGOT PART OF NIH AND OUR ADHAVEICATES AND SUPPORTERS BECAUSE OF THE WAY IN WHICH THIS DID A NUMBER MOST VISIBLY SUPPLYING ADDITIONAL FUNDING FOR FOUR PROJECTS: THE CANCER MOONSHOT, THE ALL OF US PRECISION MEDICINE INITIATIVE, THE BRAIN INITTIAIVE IT AND A REGENRATIVE MEDICINE INITIATIVE BUT ALSO HAD A NUMBER OF OTHER FEATURES IN IT SOME POLICIES THATY WOO WERE GLAD TO HAVE RESOLVED. ONE OF WHICH NOW GIVES THE NIH DIRECTOR THE AUTHORITY NOT JUST TO TRY TO PROVIDE EXORATIONS ABOUT DATA ACCESS BUT ACTUALLY TO REQUIRE IT WHICH WAS HELPFUL TO US, A VARIETY OF OTHER THINGS THAT WE HOPED FOR, BUT ONE OF THE THINGS THAT THEY FOCUSED ON IS THE VERY REASON THAT WE'RE HERE TODAY. SPECIFICALLY, THEY MANDATED AND DIANEA BIANCI WILL SHOW YOU THE ACTUAL LANGUAGE OF THE BILL SHORTLY, THAT NIH HOLD WITHIN THIS WORKSHOP WITHIN THE 180 DAYS OF THE SIGNING OF THAT BILL SO WE'VE MADE IT WITHIN THE 180 DAY WINDOW AND THIS WORKSHOP SHOULD THEN INFORM THE DIRECTOR'S MODIFICATION OF NIH POLICY ON THE INCLUSION OF UNDERREPRESENTED POPULATIONS WHICH I WILL THEN BE REQUIRED TO SUBMIT TO CONGRESS. SO THIS IS AN OPPORTUNITY TO TAKE WHAT WE KNOW OURSELVES AND WHAT THE CONGRESS REPRESENTING THE AMERICAN PUBLIC IS ASKING US TO DO AND LOOK CLOSELY AT OUR CURRENT APPROACH TO INCLUSION AND SEE WHAT WE MIGHT DO TO BE AS RESPONSIVE AS POSSIBLE. THINGS YOU WILL TALK ABOUT ON THE LIFE SPAN IN THE EARLY STAGES, THE LEFT SIDE OF THIS PARTICULAR NICE BIT OF ART WORK, WE WILL UNDOUBTEDLY WANT TO TALK ABOUT WHETHER THERE ARE THINGS WE SHOULD DO, IN TERMS OF INCLUSIVENESS OF CHILDREN TO IMPROVE OUR CURRENT ABILITY, TO UNDERSTAND WHAT WE'RE DOING AND TO REPORT IT AND PERHAPS ONE OF THOSE THINGS WILL BE WHETHER THERE SHOULD BE A DIVISION INTO AGE GROUPINGS THAT ARE SOMEWHAT MORE SPECIFIC THAN SOMEWHERE BETWEEN ZERO AND 18 AND THAT WILL NO DOUBT GENERATE SOME DISCUSSION IF WE'RE GOING TO DO THAT. ARE WE TALKING ABOUT THE AGE, DIAGNOSIS, AGE AT ENROLLMENT, AGE AT ENDING THE TRIAL, ALL THOSE THINGS WOULD NEED TO BE THOUGHT ABOUT OF COURSE. AT THE OLDER END OF THE SPECTRUM, WHERE I THINK THERE'S ALSO CONSIDERABLE CONCERN ABOUT WHETHER WE ARE DOING A GOOD JOB OF REPRESENTING THOSE POPULATIONS, WHERE THEY MAY BE PARTICULARLY IN NEED OF RESEARCH ADVANCES. I THINK WE ALL UNDERSTAND THAT ONE OF THE PROBLEMS HAS BEEN THAT OUR CLINICAL TRIALS IN THE OLD MODEL AT LEAST, AND STILL A GOOD ONE AND STILL WILL CONTINUE TEND TO ENROLL PEOPLE WHO ARE SOMEWHAT PRISTINE IN TERMS OF THE PROBLEM THAT THEY PRESENT AND YET MANY ELDERLY INDIVIDUALS ARE NOT PEOPLE WITH ONE MEDICAL PROBLEM. THEY OFTEN HAVE SEVERAL AND THAT MAY AS A RESULT OF THE WAY IN WHICH WE WRITE EXCLUSIONS, MANY OF THEM DON'T END UP HAVING THE CHANCE TO PARTICIPATE AND WE DON'T LEARN ABOUT. THAT THE OTHER HAND, I THINK THE FACT WE ARE SHIFTING AT LEAST A SIGNIFICANT AMOUNT OF OUR THINKING IN CLINICAL TRIALS TOWARDS PRAGMATIC TRIALS ALLOWS MUCH MORE CONSIDERATION OF BEING INCLUSIVE OF INDIVIDUALS WHO DON'T COME INTO THIS KIND OF CIRCUMSTANCE WITH A PROBLEM LIST THAT ONLY HAS ONE ENTRY AND AGAIN I THINK THAT COULD BE A VERY IMPORTANT PART OF THE DISCUSSION IN TERMS WHERE WE WANT TO GO. BECAUSE IF THERE'S AN ACCUSATION THAT I HEAR ABOUT FROM TIME TO TIME ABOUT THE WAY IN WHICH NIH CONDUCTED CLINICAL TRIALS, IT'S THAT OFTEN TIMES, WE ARE SEEN AS HAVING TRIALS THAT ARE NOT VERY REPRESENTATIVE OF THE REAL WORLD BECAUSE MANY OF THE PEOPLE THAT WE WOULD WANT TO EXTRAPOLATE OUR CONCLUSIONS TOO ARE MORE COMPLICATED BECAUSE OF WHAT WE ENROLLED IN THE CLINICAL TRIALS AND OUR CRITERIA. THAT IS ALSO SOMETHING YOU WILL WANT TO TALK ABOUT BUT FINALLY, I WANT TO SAY ALL OF THIS FITS VERY NICELY WITH THE FOCUS THAT WE HAVE HAD NOW FOR SEVERAL YEARS ON OUR CLINICAL TRIALS PORTFOLIO AND THE WAYS IN WHICH WE HAVE BEEN TRYING OVER THE COURSE OF TIME TO COME UP WITH WAYS TO MAKE THOSE DESIGNS MORE POWERFUL. THE DATA ACCESS ISSUES AND MUCH MORE SIGNIFICANT NOW THAT WE HAVE, AFTERALL A CLINICALTRIALS.GOV, WITH A MANDATED OPPORTUNITY TO BOTH COLLECT THE ORIGINAL STUDY INFORMATION ABOUT THE PLAN BUT ALSO TO HAVE ALL THE DATA IN A SUMMARY FORM ACCESSIBLE WITHIN 12 MONTHS AFTER CLEBLGHTING THE CLAOF THE DATA POINT. MEAN WHAT IS WE'RE DOING IN THE CLINICAL TRIALS WILL BE EVEN MORE ACCESSIBLE FOR LOTS OF PEOPLE TO LEARN FROM AND CHANGE THE PRACTICE OF MEDICINE AS QUICKLY AS POSSIBLE SO THAT THE FINDINGS WE COME UP WITH CAN BE EXTRAPOLATED TO LOTS OF THE APPROXIMATE UBIQUITINNATION LICK. THOSE CLINICAL TRIALS RESULTS TO BE NUANCED AND IF THEY WERE DONE ON CHILDREN TO KNOW SOMETHING MORE ABOUT THE AGES OF THOSE CHILDREN AND IF THEY WERE DONE ON ELDERLY INDIVIDUALS TO FIGURE OUT, OKAY, WHAT COULD WE LEARN TRUSTEES THIS THAT WOULD EXTRAPOLATE TO THE BROADER POPULATION AND DID WE IN FACT DO A GOOD JOB OF HAVING ENROLLMENT IN THOSE CLINICAL TRIALS THAT COULD BE EXTRAPOLATED. SO THE TIMING'S REALLY GOOD. THE PEOPLE IN THE ROOM ARE THE RIGHT ONES TO HELP US WRESTLE WITH THIS. WE ARE VERY SERIOUSLY GOING TO BE LOOKING IF ARE YOUR INPUT, THE MEETING HAS BEEN ORGANIZED TO HAVE THE APPROPRIATE ISSUES PUT ON THE TABLE HERE THIS AFTERNOON, BUT A LOT OF WHAT WE'RE EXPECTING TO COME OUT OF THIS WILL BE CARRIED OUT IN THE WORKING GROUPS WHO WILL UNDOUBTEDLY ROLL UP THEIR SLEEVES LATER TODAY AND THEN REPORT BACK TOMORROW MORNING ABOUT WHAT YOUR CONCLUSIONS HAVE BEEN SO THAT THEY CAN BE APPROPRIATELY SYNTHESIZED. SO I'M REALLY LOOKING FORWARD TO HEARING THE RESULTS OF THOSE DELIBERATIONS AND I'M SURE I WILL BE GETTING THOSE FED BACK TO ME IN A TIMELY FASHION BY RICHARD, BI DIANEA, BOY THE REST OF YOU WHO HAVE GOTTEN TOGETHER HERE TO MAKE THIS AN ACTION ORIENTED KIND OF GATHERING. THIS IS NOT ONE OF THOSE MEETINGS WHERE AN HOUR INTO IT EVERYBODY'S DOING THEIR E-MAIL, THIS IS NOT WHAT WE HAD IN MIND. WE WANT EVERYBODY REALLY ENGAGED TO PARTICIPATING, CONTRIBUTING. WE AIM TO PICK YOUR BRAINS IN THE BEST WAY WE CAN TO UTILIZE THIS PORT--PART IN THE RESOURCES WE HAVE TO BENEFIT PEOPLE ACROSS THE LIFE SPAN. SO I THANK YOU FOR THE CHANCE TO SAY WORDS TO YOU. I WISH I COULD STAY FOR THE REST OF THE MEETING. THERE ARE ABOUT 39,000 THINGS HAPPENING THIS WEEK AND I WILL HAVE TO RUN OFF AND DEAL WITH THE REST OF THEM. BUT I WILL COUNSELED ON GETTING A FULL REPORT AND I AM EXPECTING IT WILL BE INTERESTING AND ACTIONABLE. SO THANK YOU VERY MUCH. [ APPLAUSE ] >> THANK FOR BEING HERE AS WELL TO INTRODUCE THE MEETING FRANCIS DID WONDERFULLY WELL. I WOULD JUST ADD IN THE MATTER OF OLDER ADULTS THIS MEETING REP REFLECTS THE PROGRESS WE HAVE HAD, WE HAVE HAD THE HEALTH AND WELL BEING OF GOOD NUMBER AT LEAST OF MEN AND WOMEN SO THERE ARE MORE AND MORE LIVING INTO OLDER AGE AND MORE CLINICAL TRIALS TO IMPROVE HEALTH STATUS AND OFTEN AS COMLEX SOLUTIONS THAT FRANCIS ALLUDED TO WHICH HAS BEEN PAST FOR REASON OF EXCLUSION OF STUDIES NOW COMES A COMPELLING TOPIC FOR THOSE STUDIES. THERE HAVE BEEN A NUMBER OF REPORTS OVER THE PAST YEARS ABOUT THE WAYS IN WHICH INVOLVEMENT OF OLDER ADULTS HAS BEEN UNDERREPRESENTED AT NIH. AT NIH WE DID A STUDY AS WELL AND FOUND INDEED FOR MANY OF THE MOST COMMON CONDITIONS WHICH ARE PREDOMINANTLY CONDITIONS AND DISEASES OF OLDER ADULTS, CANCER HEART DISEASE ACCIDENT ET CETERA THERE WAS GROSS REPRESENTATION OF THOSE AND REPORTS OF THOSE EFFECTED. THERE HAVE BEEN SUBSEQUENT STUDIES, YOU WILL HEAR FROM DR. BOIGOIS, AND WE WILL LEARN LESSONS FROM THESE. I DON'T BELIEVE THAT THESE ARE BASED ON PREMEDITATED AGES AND AN INTENT TO EXCLUDE, THEY'RE LARGE CONSEQUENCES FOR FAILING TO ACCOUNT FOR THE NEEDS OF EVALUATING INTERVENTIONS, CLINICAL STUDIES AND TRIALS AND REPRESENTATIVE TO THOSE OF WHOM THEY WILL BE APPLIED SO WILL CHALLENGE IS SUBSTANTIAL TO YOU. WE NEED TO DO MORE, I THINK THANNICISM LE TO EXORT--THAN SIMPLY TO EXORT TO THE USE OF DIVERSE PROPERLY, THEY CAN BE PROPERLY CONSTRUCTED SO THEY ARE VALID. THEY LEAD TO ACTIONABLE INCLUSIONS FROM COMPLEX SITUATIONS THAT DO JUSTICE TO OUR COMMITMENTS TO DOING THE BEST WE CAN TO PROMOTE THE HEALTH AND WELL BEING ACROSS THE LIFE SPAN FROM CHILDHOOD, THROUGH MIDDLE AGE AND INTO OLDER ADULTHOOD SO WITH FRANCIS I THANK YOU BEING HERE AND LOOK FORWARD TO CONSEQUENCES AND ACTIONABLE ONES AT THIS IMPORTANT MEETING. THANK YOU. [ APPLAUSE ] DIANE? >> THANK YOU. HELLO, EVERYBODY. I WOULD LIKE TO ADD MY WELCOME. I AM DIANEA BIANCI, I AM A PEDIATRICIAN SO THEREFORE I I'M THE LOGICAL PERSON TO BEGINNING THIS TALK. YOU WOULD THINK AS DIRECTOR OF THE NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT THAT'S THE LOGICAL PERSON, CORRECT? WELL YOU WOULD BE SURPRISED TO REALIZE THAT CHILD HEALTH RESEARCH IS ACTUALLY DISTRIBUTED ACROSS ALMOST ALL OF THE INSTITUTES AT NIH. SO WE HAVE THE MOST BUT THE MOST IS ACTUALLY ONLY 18% OF ALL OF THE FUNDING RELATED TO PEDIATRICS AT NIH, THE OTHER INSTITUTES COLLECTIVELY CONTRIBUTE 72%. AND THAT'S PART OF THE CHALLENGE. IT'S DIFFICULT TO SPEAK WITH ONE VOICE, WHEN THE PEDIATRIC RESEARCH IS DRIEWBTED ACROSS SO MANY INSTITUTES. SO THEREFORE, WE ARE GOING TO HAVE THIS OPPORTUNITY TO PRESENT THE RESULTS OF SOME OF THE ANALYSIS THAT OUR TEAM HAS DONE FOLLOWING THE PLANNING FOR THIS WORKSHOP. SO FIRST--I'M GOING TO START AND THEN I WILL MOVE INTO THE- FORMAL PRESENTATION, BUT AS MANY YOU KNOW BECAUSE YOU PARTICIPATED IN THE PLANNING OF THIS, THERE'S BROAD CONCERN IN THE RESEARCH COMMUNITY ABOUT INCLUSION OF CHILDREN IN RESEARCH GENERALLY AND SPECIFICALLY IN CLINICAL TRIALS AND YOU WILL SEE IN OUR ANALYSIS THAT WE DID USE THE CLINICAL TRIALS DATABASE. THE APPROPRIATE INCLUSION OF CHILDREN AND SUBGROUP ANALYSIS ARE DECISIONS MADE ON A CASE BY CASE BASIS FOR EACH INDIVIDUAL STUDY. AND AS THOSE OF YOU KNOW WHO WRITE GRANTS, INI IH POLICY REQUIRES GRANTEES TO INCLUDE CHILDREN OR EXPLAIN WHY CHILDREN ARE NOT INCLUDED AND I THINK AS FRANCIS ALLUDED TO, I THINK YOU SAID 2013 BEFORE 2016 TO 17 THE POLICY ON CHILDREN APPLIED TO CHILDREN AS DEFINED AS UNDERAGE 21. IN 2016 TO 2017, THE THRESHOLD WAS CHANGED TO 18. AND EVEN NOW, NIH GRANTEES ARE NOT CURRENTLY REQUIRED TO REPORT ON SPECIFIC AGES INCLUDED IN RESEARCH. WELL, HERE IS ACTUALLY ACT AS TAKEN FROM THE 21st CENTURY CURES ACT THAT WAS SIGNED BY PRESIDENT OBAMA IN DECEMBER AND THE ACT WAS TO ACCELERATE THE DISCOVERY DEVELOPMENT AND DELIVERY OF 21st CENTURY CURES AND FOR OTHER PURPOSES AND ONE OF THE SUBSECTIONS WAS THE APPROPRIATE AGE GROUPINGS IN CLINICAL RESEARCH, INPUTS FROM EXPERTS. SO YOU'RE ALL EXPERTS. THAT'S WHY YOU'RE HERE AND I BELIEVE THAT TODAY IS LIKE EXACTLY 180 DAYS AFTER THE ENACTING OF THE WORKSHOP SO TODAY IS THE LAST POSSIBLE DAY WE COULD HAVE THIS WORKSHOP. AND THE CHARGE IS TO PROVIDE INPUT ON APPROPRIATE AGE GROUPS TO BE INCLUDED IN RESEARCH STUDIES INVOLVING HUMAN SUBJECTS AND ACCEPTABLE JUSTIFICATIONS FOR EXCLUDING PARTICIPANTS FROM A RANGE OF AGE GROUPS FROM HUMAN SUBJECT RESEARCH STUDIES. NOW ACTUALLY NICHD DID AN ANALYSIS IN 2008. THIS ONLY APPLIED TO NICHD FUNDED GRANTS IN 20--2007. AND THIS JUST SHOWS YOU THE MAJOR REASONS AND THE NUMBERS IS ACCORDING TO THE CATEGORIES IN WHICH THE EXCLUSIONS ARE GIVEN BUT THE THREE BIGGEST CATEGORIES& WERE NUMBER ONE, THE CONDITION BEING STUDIED IS NOT RELEVANT FOR CHILDREN. NUMBER TWO, A SEPARATE STUDY IS WARRANTED OR PREFERABLE BECAUSE OF ADULT CHILD DIFFERENCES OR THERE WERE OTHER REASONS SO THOSE ARE REALLY THE THREE MOST SIGNATURES THIF CANT REASONS FOR EXCLUDING CHILDREN UNDER AGE 21 AT THE TIME BECAUSE THAT WAS BEFORE 2016 TO 2017. SO THOSE ARE THE BACKGROUND INTRODUCTORY REMARKS SO NOW I WILL GET INTO THE ANALYSIS OFLET DAILY BASIS THEA FROM NIH WITH REGARD IT INCLUSION OF CHILDREN. AND BEFORE I BEGIN, I WOULD LIKE TO ACKNOWLEDGE THE WONDER TEAM FROM OUR OFFICE OF SCIENCE POLICY, SCIENCE POLICY REPORTING AND PROGRAM ANALYSIS. THE ASPR TEAM ALONG WITH THE CONTRACTING TEAM, THE MAYA TECH TEAM AND THERE'S A CAST OF THE PEOPLE, SOME OF THEM IN THE ROOM AND THEY DID THE HEAVY LIFTING ON THIS. ALTHOUGH I ASKED MANY QUESTIONS AND THEY EXPLAINED IT ALL TO ME SO IF I CAN UNDERSTAND IT YOU CAN UNDERSTAND IT. SO THE FIRST ANALYSIS THAT WAS DONE WAS TO LOOK DURING THE PERIOD 2007 TO 2016, A 10 YEAR PERIOD TO LOOK AT ALL OF THE GRANTS THAT WERE SUBMITTED AT THAT TIME TO SEE HOW MANY OF THEM PLANNED TO INCLUDE CHILDREN UNDER AGE 21. AND OVER THAT 10 YEAR PERIOD, YOU CAN SEE HERE, THAT IT'S PRETTY STEADY AT ABOUT 64 TO 65%. IF YOU LOOK AT THE BREAK OUT FOR JUST ONE YEAR WHICH IS FISCAL YEAR 2016OT RIGHT, IN THE BROWN, YOU SEE THE GROUP OF SUBJECTS THAT WERE PLANNED TO BE INCLUDED UNDER AND UP UNTIL INCLUDING AGE 21. FOR THE GRAY AREA, WHICH IS 36% OF THE POPULATION, ONLY ADULTS WERE PLANNED TO BE STUDIED AND IN THE GREEN, ONLY SEVEN% WERE EXCLUSIVELY CHILDREN. SO CAN YOU SEE THE MAJORITY OF THE PLANNED SUBJECTS WERE CHILDREN AND ADULTS. NOW WHAT WERE THE MAJOR LIMITATIONS OF THESE DATA ON INCLUSION OF CHILDREN UNDER AGE 21 IN THIS 10 YEAR PERIOD. WELL, FIRST OF ALL AS I'VE SAID, AT THAT TIME, THE CHILDREN WERE DEFINED AS INDIVIDUALS UNDER AGE 21 ASK MOST PEOPLE THINK OF CHILDREN AS UNDER AGE 18. THE INFORMATION IN THE GRANT APPLICATIONS WAS PERSPECTIVE SO IT ONLY INDICATED IF THE PI PLANNED TO INCLUDE CHILDREN NOT WHETHER THEY ACTUALLY INCLUDED CHILDREN IN THEIR PROPOSAL. --AT THE END OF THE PROPOSAL. THE INFORMATION OFTEN DESCRIBED WHETHER CHILDREN WOULD BE EXCLUDED RATHER THAN SPECIFIC EFFORTS WOULD BE MADE TO INCLUDE THEM. FOR MANY CLINICAL RESEARCH NETWORKS, THOSE WHO ARE NOT FULLY DEVELOPED AT THE TIME OF THE GRANT APPLICATION AND INCLUDING CHILDREN IN THIS STUDY DOES NOT NECESSARILY MEAN THAT THE DAY WILL BE ANALYZED BY AGE, OR THAT IT IS SCIENTIFIC LOW APPROPRIATE TO DO SO. SO I'M GOING TO PRESENT IN THE NEXT FEW MINUTES, THE RESULT OF THE NICHD TEAM'S ANALYSIS OF THE NIH DATA AND THE STUDY WAS PERFORMED IN TWO PARTS.& SO THE FIRST WAS AN ANALYSIS OF WHAT THE RESEARCHERS SAID THEY WERE GOING TO DO IN THEIR GRANT APPLICATIONS. AND THE SECOND WAS A REVIEW OF A MAJOR PUBLICATION. SO ONE PUBLICATION WAS SELECTED REPRESENTATIVE OF--AT THE CONCLUSION OF THAT GRANT OF THE WORK THAT WAS ACTUALLY IN INDICATING THE ACTUAL PARTICIPANT COHORT FOR THAT PARTICULAR STUDY. THE TEAM--THERE WERE INDEPENDENT TEAMS THAT CODED GRANTS ON ONE SIDE AND PUBLICATIONS ON THE OTHER SIDE. THE GRANTS AND THE PUBLICATIONS WERE REVIEWED IN THEIR ENTIRETYY AND THE DATA WERE EXTRACTED ON THE DATA IN THE STUDY, EXCLUSION KRIST ITERRIA AND THE PLANS FOR ANALYSIS AND AGE WAS CODED ACCORDING--DR. COLLINS MENTIONED THIS--THAT THE DIFFICULTY IN DECIDING WHAT AGE TO INCLUDE. SO FOR THIS ANALYSIS, AGE WAS CODED, ACCORDING TO AGE AT ENROLLMENT AND LONGITUDINAL AND FOLLOW UP STUDIES AT THE TIME OF DATA COLLECTION. AND USING PUB MED AS A SOURCE, PUBLICATIONS ASSOCIATED WITH GRANTS WERE SCREENED TO IDENTIFY THE MAIN FINDING ASSOCIATED WITH THE CLINICAL TRIAL. AND THEN EACH GRANT OR PUBLICATION WAS THEN REVIEWED BY TWO-FOUR CODERS AND ANY DISCREPANCIES WERE DISSOLVED BY DISCUSSION OR CALIBRATION PROCESS. SO THIS SHOWS YOU THE MULTIPLE DATA SOURCES THAT WERE USED FOR THE GRANTS THAT WERE INCLUDED IN THIS PARTICULAR ANALYSIS. SO AT THE END OF THE DAY, THERE WERE 300 WELL 36 SELECTED OVER A FIVE YEAR PERIOD BETWEEN 2007 AND 2011, INITIALLY USING THE QUERY QVR, WE'RE BIG ON ABBREVIATIONS HERE. THE INCLUDED GRANTS HAD TO HAVE CLINICAL TRIAL.GOV NUMBER AND THEIR CODES HERE, NOW AT THE TIME, AGAIN, IT WAS ONLY UNDER AGE 21 IN THIS GROUP, BUT YOU WILL SEE ANALYSIS THAT INCLUDE UNDERAGE 21 AND UNDER AGE 18. UNDER AGE 21 WAS ACCESSIBLE FROM THE FORMAL DATA BUT UNDER AGE 18 HAD TO BE MANUELLY COLLECTED BY THE TEAM BECAUSE IT WASN'T CODED AS SUCH DURING THIS TIME PERIOD. ON THE RIGHT SIDE, ADDITIONAL DATA WERE INCLUDED FROM CLINICAL TRIALS.GOV. THAT SITE. THE TRIAL HAD TO BE COMPLETED OR CLOSED. IT HAD TO BE A PHASE THREE CLINICAL TRIAL AND THE CTSAs WERE EXCLUDED FROM THIS ANALYSIS. SO WITHIN THAT END OF 336 CLINICAL TRIALS, WE GOT THE FOLLOWING INFORMATION. SO AGAIN, LOOK AT HOW WIDELY DISTRIBUTED ACROSS THE ICs THE CLINICAL TRIALS INVOLVING CHILDREN ARE DISTRIBUTED. SO VIRTUALLY ALL INCLUDE CHILDREN, THE NATIONAL INNSITUTE ON AGING IS NOT HERE PROPERTILY. BUT MANY OF THE OTHER INSTITUTES ARE HERE. AGAIN, NICHD HAS THE MAJORITY OF THEM HAS THEM AS YOU WOULD EXPECT BUT THE NATIONAL CENTER FOR DRUG ABUSE HAS THE NATIONAL CANCER AND LUNG AND BLOOD INSTITUTE AND THE NATIONAL INSTITUTE OF MENTAL HEALTH ARE THE OTHER MAJOR EN--STRATEGIESITUTES THAT ARE FUNDING CHILD HEALTH RESEARCH. AND THERE ARE--WERE IN THIS ANALYSIS OVER 130 DISTINCT CONDITIONS REPRESENTED. SO I THINK IT'S USEFUL TO LOOK AT THESE DIFFERENT CONDITIONS INCLUDING SUBSTANCE ABUSE, CANCER, HIV/AIDS, BLOOD DISORDERS, DEPRESSION, SMOKING DIABETES, INFECTION, PRETERM BIRTH, CARDIOVASCULAR EYE PROBLEMS AS MA AND OBESITY. SO, THESE WERE NOT MUTUALL EXCLUSIVEIVE. MORE THAN ONE CATEGORY COULD ARKTS PEER IN THE ABSTRACTION OF THE GRANT. SO HERE'S THE FIRST QUESTION OF THE NIH PHASE THREE CLINICAL TRIAL GRANTS THAT PLAN TO INCLUDE CHILDREN UNDER AGE 21, WHAT PROPORTION PLAN TO INCLUDE CHILDREN UNDER AGE 18? SO HERE, IN THE BLUE, YOU SEE 52% OF THE STUDIES PLANNED TO INCLUDE CHILDREN UNDER AGE 18 AND THOSE--THERE'S A FAIRLY EACH BREAK DOWN IN TERMS OF THE PROPORTIONS. SO, YOU KNOW, IT'S ROUGHLY A QUARTER OF EACH OF THOSE ARE IN THE DIFFERENT INCREMENTS. ALTHOUGH AGAIN, THEY'RE NOT--MUTUALLY EXCLUSIVE, NOTICE THAT 45% OF THE PHASE THREE CLINICAL TRIAL GRANTS HAD NO PLANS TO INCLUDE CHILDREN AT ALL AND THREE% OF THEM WERE MISCODED. AND THE OTHER THENG I WANT TO MENTION IS--THING I WANT TO MENTION IS YOU WILL SEE TWO DIFFERENT COLORS OF PIES. WHEN YOU SEE THE ORANGE AND BLUE, WE'RE REFERRING TO INCLUSION AND WHEN YOU SEE THE YELLOW AND THE GREEN, WE'RE REFERRING TO ANALYSIS. SO WE DID THAT SO YOU WOULDN'T GET CONFUSED. SO HERE'S THE YELLOW AND GREEN. SO HERE WE ASK THE QUESTION IN WHAT PROPORTION OF THE GRANT APPLICATIONS DID RESEARCHERS PLAN TO ANALYZE DATA BY AGE? AND THIS IS A BIG TAKE HOME MESSAGE HERE, 60% OF THE GRANT APPLICATIONS DID NOT PLAN TO ANALYZE BY AGE. 70% DID AND EIGHT% WERE NOT APPLICABLE AND 15% WE'RE GOING TO ANALYZE BY AGE IF THERE WAS A SCIENTIFIC REASON TO DO SO. SO IF THE INITIAL ANALYSIS OF THE DATA SUGGESTED SOMETHING INTERESTING, THEN THEY WILL WOULD GO BACK BUT 60% DID NOT PLAN TO ANALYZE BY AGE. SO NOW, WE LOOK AT THE PUBLICATIONS BECAUSE OF THE CONCERN THAT PEOPLE ARE NOT PUBLISHING FROM THEIR CLINICAL TRIALS, FORTUNATELY WE FOUND THAT WAS NOT THE CASE. IN FACT, GIVEN THAT THE END DATE OF THE TRIALS THAT WERE USED FOR THIS ANALYSIS WAS 2011, 97% OF THESE PROJECTS HAD AT LEAST ONE MAJOR PUBLICATION IN PUB MED BY APRIL OF 2017. AND 82% OF THE GRANTS HAD PUBLISHED CLINICAL TRIAL RESULTS BY APRIL 2017. SO THERE WAS AT LEAST ONE PUBLICATION, NOT THE MAJOR PUBLICATION NECESSARILY, IT COULD HAVE BEEN METHODS, COULD HAVE BEEN A STUDY DESCRIPTION BUT 82% HAD CLINICAL TRIAL RESULTS WITHIN FIVE-SEVEN YEARS AFTER THE START OF THE GRANT. AND THE PUBLICATION RATES WERE SLIGHTLY BUT NOT SIGNIFICANTLY HIGHER FOR GRANTS INCLUDING CHILDREN UNDER AGE 18. SO, AGAIN, BACK TO THE ORANGE AND BLUE. SO INCLUSION, HOW OFTEN WERE CHILDREN INCLUDED IN THE PUBLISHED RESULTS. 31% OF THE PUBLICATIONS INCLUDED CHILDREN UNDER AGE 18. 58%, AGAIN, AROUND 60% DID NOT HAVE PUBLICATIONS ENCLUEDING CHILDREN AND 11% FTION UNSPECKIFIED. NOW THIS IS INTERESTING, PEOPLE CAN SAY ONE THING IN THEIR GRANT APPLICATION BUT WHAT DID THEY ACTUALLY DO? AND WE USED THE PUBLICATIONS AS A MEASURE OF WHAT WAS ACTUALLY DONE. SO FOR THE STUDIES IN WHICH BOTH THE GRANT AND PUBLICATION REPORTED AGES 29% DEVIATED FROM THE PLAN DESCRIBED IN THE GRANT. MOST OF THEM WHICH IS THE BROWN GROUP HERE PLANNED TO INCLUDE CHILDREN IN THE STUDY BUT THEY DID NOT INCLUDE THEM IN THE PUBLISHED RESULTS. 36% ONLY PLANNED TO STUDY ADULTS, INCLUDE ADULTS AND THEY ACTUALLY DID OHM INCLUDE ADULTS. AND 35% PLAN TO INCLUDE CHILDREN AND DID INCLUDE CHILDREN. AND NOW HERE WE HAVE THE ANALYSIS INLET YELLOW AND GREEN, AGAIN, SO 36% OF THE PUBLICATION ANALYZED DATA BY AGE BUT 64% DID NOT. WITH THE ANALYSIS BY AGE, HOW CONSISTENT WITH THE PUBLISHED RESULTS WITH THE RESEARCH PLAN AS WRITTEN? SO FOR THE STUDIES WITH INFORMATION ON BOTH THE PLANNED AND ACTUAL ANALYSIS, 36% WHICH IS 19 + 17 DEVELOPMENTAL ENDOCRINOLOGYIATED FROM THE ANALYSIS PLAN. SO IN THE DARK GREEN THEY DIDN'T SAY THEY WERE GOING TO ANALYZE IN THEIR GRANT APPLICATIONS BUT THEY DID. AND THEN, IN THE BROWN, THEY SAID THEY WERE GOING TO ANALYZE BUT THEY DIDN'T. YELLOW, 50% OF THE TIME, THEY DIDN'T PLAN TO ANALYZE BY AGE AND THEY DIDN'T, THEY WERE CONSISTENT IN THAT. SO ONLY THIS SMALL PIECE OF THE PIE, THE 14% PLAN TO ANALYZE BY AGE AND ACTUALLY DID. SO YOU CAN ALREADY SEE, I THINK YOU HAVE YOUR WORK CUT OUT FOR YOU. SO, SUMMARY OF THE RESULTS OF THIS SMALL BUT IMPORTANT ANALYSIS AND I SHOULD MENTION THAT THE ANALYSIS, THE TEAM BASICALLY STARTED AFTER THE SIGNING OF THE ACT SO REALLY THE ANALYSIS BEGAN IN MARCH AND HERE WE ARE JUST THE VERY, VERY BEGINNING OF JUNE. SO IN THIS SHORT PERIOD OF TIME WE ALREADY HAVE SOME SUBSTABT STANTIVE RESULTS WITH REGARD TO INCLUSION AS WELL AS ANALYSIS. SO, THE MAIN TAKE HOME POINTS ARE THE FOLLOWING: 65% OF ALL NIH GRANTS-SO THIS IS THE DATA I SHOWED AT THE BEGINNING--PLAN TO ENCLUED CHILDREN UNDER AGE 21. BUT ONLY ABOUT HALF OF THOSE, THIS WAS THE MANUEL DATA THAT I SHOWED LATER ON PLANNED TO INCLUDE CHILDREN UNDER AGE 18. NOWADAYS IF WE WERE TO DO THE STUDY WITH CONTEMPORARY DATA WE WOULD HAVE AUTOMATICALLY THE DATA UNDER AGE 18 BECAUSE IT'S CODED AS SUCH. I MEAN THEY'RE GOING TO SAY YES OR NO ABOUT 18. WE WON'T NECESSARILY KNOW WHAT THEY'RE ACTUALLY DOING. WITH REGARD TO THE ANALYSIS, IN 60% OF NIH PHASE THREE CLINICAL TRIAL GRANTS THAT PLAN TO INCLUDE CHILDREN RESEARCHERS DID NOT PLANT-- >> [INDISCERNIBLE] >> --SORRY. RESEARCHERS DID NOT PLAN TO ANALYZE RESULTS BY AGE. I THOUGHT SIRI WAS ASKING ME A QUESTION. VERY FREAKY. [LAUGHTER] SO THE GOOD NEWS IS OVER 80% OF THE NIH PHASE THREE CLINICAL TRIAL GRANTS THAT WERE STUDIED DURING THAT 2007 TO 2011 WIND O PUBLISHED RESULTS WITHIN FIVE-SEVEN YEARS OF THE FUNDING. THOSE WERE THE MAJOR CLINICAL TRIAL RESULTS. --THEY DID NOT INCLUDE CHILDREN UNDERAIN AGE IN THE PUBLISHED RESULTS. GOT ONE MORE HERE. AND 36% OF THE GRANTEES IN THE ANALYSIS DIFFERED FROM THEIR ORIGINAL ANALYSIS PLAN IN THEIR PUBLISHED RESULTS. SO I THINK YOU CAN SEE FROM THIS DATA SET OF 336 STUDIES PERFORMED ACROSS DIFFERENT INSTITUTES THAT THERE'S A DISCREPANCY BETWEEN THE PLANS AND THE ACTUAL RESULTS AT THE END OF THE STUDY. SO I'D LIKE TO THANK YOU FOR YOUR ATTENTION AND I GUESS WHEN WE BREAK, WE WILL BE TAKING QUESTIONS, I THINK? DO ARE WE DOING QUESTIONS? DO WE KNOW. OKAY. HAPPY TO TAKE QUESTIONS. [ APPLAUSE ] YES? PLEASE INTRODUCE YOURSELF, TOO. >> WILLIAM DALE FROM THE CITY OF HOPE CANCER CENTER. I'M A GERIATRICIAN BUT I'M CURIOUSOT PUBLISHED RESULTS HOW MUCH OF THAT DO YOU THINK IS THE AUTHOR'S AND HOW MUCH WOULD BE AT THE EDITORIAL OR REVIEW LEVEL WHERE THEY TRY TO INCLUDE CHILDREN? IT TURNED OUT THEY WERE NOT SIGNIFICANT IN SOME WAY THAT MATTERED? SO THEY DIDN'T GET REPORTED BECAUSE OF THE EFFORTS TO REPORTS OF ONLY POSITIVE RESULTS. AND HOW MUCH DO YOU THINK IS THE AUTHOR'S JUST COULDN'T FOLLOW THROUGH ON THEIR INTENT FOR WHATEVER REASON BECAUSE WE FIND AT THE OTHER END OF THE AGE SPECTRUM IF IT'S NOT SIGNIFICANT THEN YOU JUST INCLUDE THEM ANYWAY AND PEOPLE WON'T WANT AN AGE BREAK DOWN NECESSARILY. >> YEAH, SO THAT'S INTERESTING NYEAH, THAT'S AN INTERESTING QUESTION AND FULL DISCLOSURE IN MY OFFHOURS I'M A JOURNAL EDITOR. AND WE'VE NEVER ASKED AN AUTHOR TO NOT INCLUDE INFORMATION. I BELIEVE IN, YOU KNOW SHARING AS MUCH INFORMATION AS POSSIBLE. SO I THINK IT WOULD BE DIFFICULT TO KNOW WHY IT WASN'T INCLUDED. MY GUESS IS BECAUSE THEY'RE NOT REALLY THINKING ABOUT IT IS THE MAIN REASON BUT I WOULD ASK THE TEAM, THE ASPR TEAM IF YOU HAD ANYTHING TO ADD. SARAH, YEAH? >> GO TO THE MICROPHONE PLEASE? >> HI, HELLO. I'M SARAH GLAVIN, FROM NICHD, PAT OF THE TEAM THAT DID THE ANALYSIS. THE DATA WHERE WE DESCRIBED WHO WAS INCLUDED OR NOT INCLUDED BOTH INFORMATION FROM THE DESCRIPTIVE SECTION OF THE PAPER AS WELL AS RESULTS. SO EVEN IF THERE WAS NO AGE IN THE RESULTS WHEN WE'RE TALKING ABOUT WHETHER THEY WERE INCLUDED WERE ALSO LOOKING AT THE DESCRIPTIVE PART OF THE PAPER AND THE DESCRIPTION OF THE SAMPLE IF THAT HELPS. >> THANK YOU. >> ANOTHER QUESTION OVER HERE. >> HI, I'M BETH AT THIS AT TIPTON FROM COLUMBIA. IT STRIKES ME AS REASONABLE THAT YOU WOULD FIND THAT MOST PEOPLE ARE NOT DOING ANALYSIS BY AGE BECAUSE STUDIES ARE POWERED BY THE AVERAGE TREATMENT EFFECT AND NOT FOR AGE-SPECIFIC EFFECTS SO I THINK THAT'S SOMETHING TO KEEP IN MIND SOMEHOW IN THIS CONVERSATION THROUGHOUT IT THAT IF YOU WERE TO HAVE REPORTED AT A HELPED% HAD ACTUALLY REPORTED BY AGE ANALYSIS, I THINK WE WOULD BE WORRY BODY FISHING AND PEEM--PEOPLE LOOKING FOR THINGS THAT ARBITRATE THERE TO START WITH. >> YEAH, BUT BASED ON THE DISTRIBUTION OF CONDITIONS, WE EXPECTED MAYBE TO SEE PEAKS AT THE NEOINATE, YOU KNOW THE LESS THAN ONE YEAR AND AT THE ADOLESCENT MEN, THERE WERE DRUG ABUSE, SMOKING, THINGS YOU WOULD EXPECT, YOU KNOW MAYBE TO SEE EFFECTIVE TEENAGERS MORE. SO THE FACT THAT YOU--YOU KNOW YOU REALLY DIDN'T SEE THAT INTRIEWKS. >> SO MY QUESTION THERE WOULD BE IN THE STUDY DESIGN, SO YOU'VE ASKED THE LITERATURE IF THEY INCLUDED PEOPLE OF DIFFERENT AGE BUT IS IT POSSIBLE TO KNOW IN THE GRANT PROPOSALS IF THEY PROPOSED TO DO ANALYSIS BY AGE? >> YES. >> AND IF THEY POWERED THEIR STUDIES FOR THOSE ANALYSIS? >> YES, I BELIEVE THAT'S ONE OF THE THINGS YOU WERE LOOKING FOR. >> YEAH, THAT SEEMS TO BE MORE IMPORTANT IN MY MIND IF THEY ACTUALLY PLAN TO DO THOSE ANALYSIS THAN IF THEY JUST DID THEM AT THE END. >> RIGHT. YES. OTHER QUESTIONS? >> DIANEA? >> DIANEA? OVER HERE, I'M SORRY. HI. >> I'M WITH THE CHAIR OF PEDEIATICS IN SEATTLE, IS THERE ANYWAY TO ASSESS THE IRB PROCESS AND HOW THAT EFFECTS THE ENROLLMENT AND THE STUDIES. THE POODIATRIC IRBs IN MY EXPERIENCE ARE EXTREMELY CAREFUL AND DELAY ENROLLMENT IS OFTEN DELAYED BASED ON THE APPROVAL PROCESS. >> YES, SO I DOUBT THAT THAT WOULD BE REFLECTED IN THE GRANT OR THE PUBLICATIONS IF THERE HAD BEEN A DIFFICULTY BUT I WOULD SAY THAT'S REALLY A QUESTION FOR THE WORKING GROUPS. THAT, MAYBE THAT NEEDS TO BE SOMETHING PUT ON THE TABLE. WHAT IS THE ROLE OF THE IRB IN GETTING, YOU KNOW--GETTING APPROVAL SAFE FOR PARTICULARLY VULNERABLE POPULATIONS OR PERHAPS TEENAGERS WHERE YOU'RE CONCERNED ABOUT CONFIDENTIALITY OF DATA. SO I JUST THINK IT WOULD BE DIFFICULT TO KNOW IF THERE HAD BEEN A PROBLEM, WOULD SOMEBODY REALLY SAY THAT IN THEIR PUBLICATION. >> SCOTT DENNY FROM THE IN UNIVERSITY. I THINK YOU MADE AN INCREDIBLY COMPELLING CASE FOR REPORTING REQUIREMENTS HERE. YOU KNOW OBVIOUSLY PEOPLE HAVE PLANNED AND THEY DON'T NECESSARILY DO WHAT THEY PLAN WHICH HAPPENS IN LOTS OF STUDIES AND I THINK THE OTHER THING IS THAT WHEN PEOPLE HAVE SPECIFIC REPORTING REQUIREMENTS IT ACTUALLY DOES MODIFIED BEHAVIOR AND I JUST WONDERED IF YOU HAD ANY COMMENTS ON EITHER OF THOSE THINGS. >> YEAH, SO I THINK THAT'S SOMETHING TO--THESE INITIAL PRESENTATIONS ARE REALLY TO GET YOUR ENGINES RUNNING AND INSPIRE YOU TO ASK QUESTIONS AND DISCUSS, SO, YOU KNOW WE HAVE SOME DATA FOR YOU TO REACT TO. I LOOKED AT IT AND SAID, YEAH, I WAS KIND OF SURPRISED THAT THE NUMBERS WERE HIGH, BUT THAT'S MY OPINION ONLY. NOT TO INFLUENCE THE WORKING GROUP. >> BERNADETTE WITH NEW YORK UNIVERSITY. THIS WAS A GREAT PRESENTATION AND GETTING BACK TO THE STATISTICIAN FROM COLUMBIA'S POINT. SO YOU KNOW THERE'S OBVIOUS LOW A LOT OF CONCERN FOR [INDISCERNIBLE] AND I THINK SOMETIMES THAT'S THE CONTROLLER OF BANK THAT NOBODY WANTS TO GELT OUT OF. --GET OUT OF. A LOT OF WORK I DO IS AN INCLUSION OF MINORITY POPULATIONS INTO CLINICAL TRIALS ISSUES OBVIOUSLY A MAJOR AREA AS WELL AND SO THIS WHOLE FOCUS ON HAVING ENOUGH--DIFFERENT POPULATIONS OR SUBPOPULATIONS OR DIFFERENT MINORITY GROUPS IN THE SAMPLE TO LOOK AT A VALID ANALYSIS BECAUSE ONE OF THE THINGS YOU REALLY WANT TO DO IS SAY, IS THERE SOMETHING DIFFERENT ABOUT USING THIS MEDICATION IN THIS GROUP AND FOR YOUR PIECE POPULATION IN DIFFERENT AGE GROUP AND I THINK WE REALLY HAVE TO THINK THROUGH, WE'RE FOCUS ON THE ALWAYS GOING TO HAVE ENOUGH POWER TO MAKE A POWER AT THE SAME TIME OR SIGNIFICANT STATEMENT BETWEEN THE NEOINATE OR THE ONE YEAR-OLD VERSUS THE 13 YEAR-OLD BUT I DON'T THINK IT DOESN'T MEAN WE SHOULDN'T PRESENT THE DATA AND I THINK PEOPLE NEED TO FEEL COMFORTABLE ABOUT THAT PRESENTATION OF DATA. I THINK THAT'S THE FIRST STEP. >> THANK YOU FOR YOUR COMMENT. YES? >> SO I MEAN WHAT I'M HEARING IS POWER IS ONE THEME. IRBs IS ANOTHER THEME. SO JUST THOSE OF YOU IN THE WORKING GROUPS. >> YEAH, THANK YOU. ONE OTHER POINT TO KEEP IN MIND IS THE INCLUSION CRITERIA, IN THE APPLICATION IS A REVIEW CRITERIA. IF IT IS NOT MENTIONED THE REVIEWERS CAN DING IT OR AT LEAST RAISE A QUESTION AND SOMEONE CAN'T BE FUNDED UNTIL THAT IS SATISFILY ANSWERED SO IT'S QUITE POSSIBLE WHEN THEY'RE DESIGNING AND WRITING AN APPLICATION, THEY WILL SAY YES FOR THE CHILDREN, AND WE ARE NOT REQUIRED TO DISSECT IT BEYOND THAT, SO STRENGTHS TO THAT APPLICATION, SOME OF THE VIEWERS DO THAT, SOMETIMES THEY MAY OR MAY NOT DO. BUT THAT IS ONE OF THE MAJOR ISSUES, BUT THE OTHER POINT IS TO EMPHASIZE THAT THE AGE OF THE CHILD IS THE AGE OF INCLUSION OF ANALYSIS IS A BIOLOGICAL VARIABLE. IT IS SAMPLE SIDE ISSUE, THERE'S NO DOUBT ABOUT IT BUT UNLESS WE BEGIN TO LOOK AT IT AS AN IMPORTANT BIOLOGICAL VARIABLE THAT CAN EFFECT OUTCOMES UNLESS YOU USE ANALYSIS, YOU WON'T FIND OUT AND EVEN NEGATIVE INFORMATION MAY BE WORTH WHILE IF IT IS REASONABLY POWERED. >> THANK YOU. AND TONSA DIDN'T INTRODUCE HIMSELF BUT HE'S CHIEF OF PREGNANCY AND NEONATAL BRANCH AT NCIHD. >> THANK YOU. >> YES, SO RELATED THAT IT MIGHT BE THAT PEOPLE WHO ARE APPLYING FOR GRANTS ARE WRITING SOMETHING, NOT NECESSARILY THINKING ABOUT SOMETHING ABOUT WHETHER THEY FOLLOW THROUGH ON& IT AND THERE ARE MANY REASONS FOR THE DISCREPANCIES BETWEEN WHAT PEOPLE SAY THEY'RE GOING TO DO AND WHAT THEY ACTUALLY DID BUT I THINK THAT'S ANOTHER TAKE HOME MESSAGE THAT THERE ARE THESE DISCREPANCIES AND QUESTION MIGHT BE, YOU KNOW WHAT'S THE APPROPRIATE WAY TO CLOSE THE LOOP AND EITHER HOLD PEOPLE'S FEET TO THE FIRE IF THEY SAY THEY'RE GOING TO DO IT, THEY ACTUALLY DO IT OR THEY HAVE A COMPELLING REASON WHY THEY DIDN'T DO IT BUT YES, YOU HAVE A QUESTION. >> BRIAN FROM NORTHWESTERN UNIVERSITY IN CHICAGO AND I WANTED TO ASK YOU A QUESTION ABOUT THE EARLIER PART OF THE PROCESS, GRANT REVIEW PROCESS WHERE YOU SAID ABOUT HALF OF THE TIME ADOLESCENCE OR CHILDREN WERE EXCLUDED BECAUSE THE CONDITION DOES NOT RELEVANT OR THAT'S THE CASE THE RESEARCHER MADE ABOUT A THIRD OF THE TIME IS THAT THEY'RE SAYING DIFFERENT STUDIES SHOULD BE DONE WITH CHILDREN IN ADOLESCENCES AND I'M WONDERING IF YOU LOOKED AT ALL FOR THE CASES IN WHICH THE REVIEW GROUPS FIND THAT TO BE AN ADEQUATE JUSTIFICATION VERSUS WHAT I PERCEIVE AS PROBABLY A FAIRLY RARE OCCURRENCE WHERE THE RESEARCH GROUP DOESN'T FIND THAT TO BE AN ADEQUATE JUSTIFICATION AND WHAT THOSE DIFFERENCES MIGHT BE. >> YEAH SO I'M RELATIVELY NEW TO NIH. I'VE BEEN MUCH MORE ON THE GRANT WRITING SIDE AND I WOULD NOT BE IN THE REVIEW PROCESS OR MAYBE SOMEONE WHO ELSE--COULD YOU ADDRESS WHAT KINDS OF QUESTIONS COME UP WHEN THERE IS A REASON WHY THEY'RE NOT USING CHILDREN? >> YES, TONSA AGAIN. YES, THERE'S A REQUIREMENT THAT APPLICANTS THEY'RE NOT INCLUDING AND HAVE THE PROVIDER JUSTIFICATION AND THAT JUSTIFICATION SCIENTIFICALLY ACCEPTABLE. SO THE REVIEWERS ARE SUPPOSED TO PINE ON THAT. SO--HOW DETAILED ANALYSIS, THE REVIEW THEY DO ON THAT POINT MAY VERY DEPENDING ON A STUDY SECTION BUT THERE IS A REVIEW KRISTITARYIA. >> YOU'RE RIGHT, I'M AWARE OF THAT CRITERIA AND I'M WONDERING HOW OFTEN--IF WE KNOW ANYTHING ABOUT THE CASES WHEN IT'S NOT DEEMED ACCEPTABLE VERSUS WHEN IT IS. >> WE DO HAVE A LOT OF DATA COME IN AND SAY, THEY SAY THAT THEY DON'T INCLUDE THIS BUT IT'S NOT ACCEPTABLE. AND THEN WE AS PROGRAM OFFICIALS IF THAT IS A FUNDABLE APPLICATION HAD TO GO BACK TO THEM AND HAVE THAT FIXED. ONE STUDY IN THE SUMMARY STATEMENT, WE CAN'T FUND IT UNTIL THAT GETS ADJUSTED. >> LAST QUESTION. >> BERNARD DRYER NYU SCHOOL OF MEDICINE AND THE AMERICAN ACADEMY OF PEDIATRICS. ON YOUR LIST OF--ON YOUR GRAPH OF VARIOUS PARTS OF THE NIH, OBVIOUSLY NICHD WAS FRONT AND CENTER, REGARDING THE--THIS IS A QUESTION, REGARDING THE ANALYSIS, THOSE GRANTS ARE ACTUALLY ANALYZED BY AGE WERE THEY PRIMARILY BY NICHD, WERE THERE ANY--IS THERE ANY PATTERN TO WHICH--WHICH OF THE PARTS OF THE NIH ARE MORE LIKELY TO DO. >> SO I HAVE TO ASK SARAH. SO OF THE ONES THAT--DID YOU DO THAT SUBSEQUENT ANALYSIS OF THE ONES THAT DID SAY THEY WOULD INCLUDE CHILDREN, ACTUALLY ENCLUEDED CHILDREN. DID YOU SEE IF NICHD WAS OVERREPRESENTED THERE? >> [INDISCERNIBLE]. >> SO YOUR HYPOTHESIS IS THAT-SHOULD HAVE. >> I HOPE THAT NIKREBS CYCLE, HD WOULD AT LEAST DO ANALYSIS. >> SORE AT LEAST INVESTIGATORS WILLED BE MORE SENSITIVE. THAT WOULD BE THE HYPOTHESIS. OKAY. GOOD. WELL THANK YOU VERY MUCH FOR YOUR ENGAGEMENT AND MOVING ON. [ APPLAUSE ] SPHRKS SO OUR NEXT SPEAKER IS DR. BORGOIS FROM HARVARD MEDICAL SCHOOL WHO WILL PROVIDELET OTHER END OF THE LIFE SPAN. >> HELLO AND THANK YOU. SO I WILL BE SPEAKING TO YOU TODAY ON THE PERSISTENT EXCLUSION OF ELDER LOW PATIENTS IN CLINICAL RESEARCH. SO, AS SOME OF YOU MAY HAVE NOTICED FROM THAT FIRST SLIDE, I'M ACTUALLY A PEDIATRICIAN BY TRAINING AND SO, I THINK THIS WARRANTS AT LEAST A QUICK EXPLANATION FOR WHY I'M STANDING HERE TODAY FOR ABOUT POOR RESOURCE USE FOR ELDERLY AS OPPOSE TO CHILDREN. SON SO ONE OF MY AREAS OF INTEREST IS PATIATRIC ACTIVITY AND THIS FIGURE IS A BIT OUTDATED BUT I HAVEN'T BEEN ABLE TO FIND ANOTHER ONE THAT DEPICTS THE ISSUE QUITE SO L. SO AS YOU HERE WITH THE LAVENDAR LINE THERE WAS A TREMENDOUS INCREASE IN THE NUMBER OF CONTROL TRIALS THAT ARE CONDUCTED START NOTHING THE 1960S. AND THIS INCREASE WAS CLEARLY NOT PARALLELLED FOR PEDIATRIC TRIALS WHICH WAS THE DARK BLUE LINE AT THE BOTTOM. SO BETTER DEFINING THESE ISSUES HAS BEEN AT THE CORE OF A NUMBER OF MY STUDIES. AND IN DOING SO, SIMILAR TO DR. BIANCI'S ANALYSIS, I LOOKED AT CLINICALTRIALS.GOV EXTENSIVELY. AS MANY OF YOU KNOW THIS IS THE LARGEST TRIAL REGISTRY AND BECAUSE OF A NUMBER OF POLICIES AND LEGISLATION MOST NONPHASE ONE TRIALS ARE MANDATED TO BE REGISTERED IN THIS REGISTRY. SO AS SUCH IT'S A VERY WELL SUITED DATA SOURCE FOR LOOKING AT OUR CLINICAL RESEARCH ACTIVITIES ANALYZING IT, MONITORING IT OVER TIME. IN THIS FIGURE HERE, I LOOKED AT ALL TRIALS THAT WERE REGISTERED JUST LAST YEAR IF 2016 AND LOOKED AT THE PROPORTION THAT WERE ELIGIBLE FOR VARIOUS AGE GROUPS DEPICTED ALONG THE Y-AXIS. AND OF COURSE, MY INITIAL INTEREST WAS OVERHERE AND YOU CAN SEE THAT OUT OF THESE 17,000 TRIALS, THERE WERE 2900, SO JUST ABOUT 16% THAT HAD ANY ELIGIBILITY FOR CHILDREN. BUT IN LOOKING AT THIS, I THINK IT'S ALSO STRIKING TO NOTICE WHAT'S GOING ON AT THE OTHER END OF THE SPECTRUM. CERTAINLY AFTER THE AGE OF 65, THERE APPEARS TO BE QUITE A DRAMATIC DROP OFF IN THE ELIGIBILITY OF OUR PATIENT POPULATION. AND SO, THIS TYPE OF FINDING ALONG WITH A NUMBER OF OTHERS MADE ME RAISE THE QUESTION OF WHETHER SOME OF THE QUESTIONS THAT I HAD BEEN LOCKING AT FOR CHILDREN, OR EVEN SOME OF THOSE APPROACHES COULDN'T BE EXTENDED TO OUR ELDERLY POPULATION. SO FOR STARTERS IN THIS IS PROBABLY FAIRLY NEEDS INTRODUCTION FOR THIS GROUP, BUT PERSON 65 YEARS OF AGE AND OLDER ACTUALLY ACCOUNT FOR A VERY SMALL PROPORTION OF OUR POPULATION. SO WHY ARE WE SO CONCERNED ABOUT THEIR EXCLUSION AND CLINICAL TRIALS. AND THERE ARE A NUMBER OF VERY STRIKING REASONS FOR THIS. FOR STARTERS ABOUT 60%, THESE ARE JUST A FEW EXAMPLES, 60% OF PATIENTS WITH CANCER ARE 65 YEARS OR OLDER. 65% OF PATIENTS ARE ABOUT TWO/THISHEDS ARE HOSPITALIZED FOR HEART DISEASE OF OUR ELDERLY PATIENTS AND GREATER THAN A THIRD OF TOTAL HELGTD CARE EXPENSES ARE SPENT IN THIS POPULATION AND ABOUT A THIRD OF ALL PRESCRIPTION DRUG COSTS. SO CERTAINLY RESEARCH IN THIS SPECIFIC POPULATION IS WARRANTIED. SO WHAT ARE THE REAL ISSUES, SO FIRST OF ALL, IT SHOULD ALSO BE MENTIONED THERE ARE A NUMBER OF CHALLENGES IN STUDYING ELDERLY PATIENTS AND THESE NEED TO BE ACKNOWLEDGED AS PART THIS PICTURE. SIMILAR TO CHILDREN ACTUALLY THERE ARE CONCERNS ABOUT THE SAFETY, RISK OF PROCEDURES CAPACITY TO CONSENT, ELDERLY PATIENTS ALSO ARE A HIGHER RATE OF CO EXISTING MEDICAL CONDITIONS WHICH MAY CONFOUND TREATMENT OUTCOMES, LEAD TO HETEROGENEITY AND TREATMENT RESPONSES AND THERE ARE A NUMBER OF PRACTICAL BARRIERS RELATED TO STUDY ACTIVITIES, DEMANDS OPERATIONS FOR EXAMPLE, ELDERLY PATIENTS MAY HAVE HEARING DEFICITS, VISUAL IMPAIRMENT BEING COGNITIVE SLOWING, FALL RISKS ALL OF THESE NEED TO BE ACCOUNTED FOR WHEN PLANNING AND CONDUCTING A TRIAL AND THIS IN TURN WILL LEAD TO SUBSTANTIAL INCREASES IN COSTS. FOR EXAMPLE, REDUCED MOBILITY MAY WARRANT HOME VISITS WHICH MAY REQUIRE ADDITIONAL STAFFING AND OTHER RESOURCES TO COMPLETE THE TRIAL. SO WHAT ARE THE REAL ISSUES AROUND THE REPRESENTATION OF ELDERLY PATIENTS IN OUR CLINICAL TRIALS. ARE THE ELDERLY BEING EXPLICITLY EXCLUDED FROM TRIALS. IS THIS BASED ON AGE ALONE OR OTHER FACTORS THAT WE NEED TO BE CONSIDERING AND IF THEY ARE EXCLUDED, ARE THE TRIALS THAT WE DO CONDUCT ACTUALLY REPRESENTATIVE OF OUR OF PAR PATIENT POPULATION, CAN WE TAKE THOSE RESULTS AND USE THEM IN CARING FOR THIS PATIENT POPULATION AND MOST IMPORTANTLY, ARE THEY WELL REPRESENTED FOR THE DISEASES THAT ACTUALLY EFFECT THEM THE MOST, THE DEC WITH HIGHEST PREVALENCE AMONG THE ELDERLY SO TODAY WHAT I WOULD LIKE TO DO IS WALK YOU THROUGH A FEW ANALYSIS THAT SHOW IMPERRIC EVIDENCE OF THE EXCLUSION OF ELDERLY PERSONS IN AN EXAM NATION OF HOW WELL WE'RE MEETING DISEASE NEEDS FOR THE ELDERLY. WITH NUANCES AROUND THESE ISSUES WHICH WILL HELP US IN OUR WORKING GROUPS ALSO ADDRESS HOW THEY MIGHT BE RECTIFIED AND AS I SHOULD MENTION THAT ALL OF WORK WAS FUNDED BY AN R21 FROM THE NIA. SO, IN THESE ANALYSIS, FOR THIS& FIRST ONE, I LOOKED AT TWO LINKED SOURCES OF AGE INFORMATION. THE FIRST ONE WAS RANDOMIZED CONTROL TRIALS THAT I PULLED FROM CLIN CLINICALTRIALS.GOV. AND FOR THIS TRIAL COHORT I LIMITED TO TRIALS THAT WERE STUDYING DRUG THERAPY FOR ASCHEMIC HEART DISEASE FOR TWO REASONS, ONE FOR DAT EXTRACTION BECAUSE THE TRIAL COHORT BECOMES SO LARGE IN THIS DATA SOURCE AND ALSO SO THEY COULD THEN ESTABLISH A COMPARATOR POPULATION AMONG REAL WORLD PATIENTS TO COMPARE PARTICIPANTS TOO. SO FOR THESE TRIALS WE LACKED AT CHARACTERISTICS, THEIR DATES OF STUDY, THE FUNDING SOURCE, SOME OF THE TRIAL DESIGN FEATURES AND OF COURSE ELIGIBILITY CRITERIA. AND FOR EACH OF THESE REGISTRY ENTERS--ENTRIES, AND FROM PUBLICATIONS YOU CAN GET INFORMATION AROUND THE PATIENT WHO IS ARE ACTUALLY ENROLLED SO THE AGE DISTRIBUTION OF PARTIC PLAN TO ANALYZE BY PARTICIPANTS AND ALSO WITH THE SAMPLE SIZE. AND THE IMPORTANT POINT HERE IS THAT WHY WE NEED TO LOCK AT PUBLICATIONS AS WELL IN THE ACTUAL ENROLLMENT IS BECAUSE OF ELIGIBILITY CRITERIA, MAY OR MAY NOT BE EQUIVALENT TO THE ACTUAL ENROLLMENT OF ELDERLY PATIENTS. SO THE ACTUAL--AS YOU ALREADY HEARD MAY NOT BE THE SAME AND THIS IS SOMETHING WE WILL COME BACK TO. SO FOR THIS ANALYSIS, IN ALL WE OOH DENTIFIED 839 TRIALS, THESE WERE REGISTERED OVER A 10 YEAR PERIOD THROUGH 2016 AND THEY ARE FAIRLY RUN OF THE MILL IN TERMS OF THEIR CHARACTERISTICS SO MEDIAN SAMPLE SIZE WAS ABOUT 120, ABOUT A QUARTER WERE FUNDED BY INDUSTRY, THE STUDY DURATION WAS JUST AROUND TWO YEARS OR UNDER TWO WREERS AND THE--YEARS AND THE MAIN DRUGS THAT WERE STUDIED WOULD BE WHAT WE EXPECT FOR PATIENTS WITH ASCHEMIC HEART DISEASE, ABOUT 42% WERE THROMBOTIC AGENTS, 16% LIPID MARKED FOR IDENTIFICATION MODIFYING AGENT AND EIGHT% WAS HYPER TENSIVE DRUGS. SO WHAT WAS STUDIED IN THIS TRIAL? SO 446 EXPLICITLY EXCLUDED ELDERLY PERSONS SO IN HALF OF THESE TRIALS THERE WERE AGE LIMITS THAT PREVENTED THE INCLUSION OF OLDER PATIENTS. AND THIS IS WHAT THIS INCLUSION LOOKS LIKE ON A BAR GRAPH. SO ALONG THE X-AX I GUESS WE'RE LOOKING AT THE MAXIMUM REPORT ELIGIBLE AGE. AND WHAT YOU CAN SEE IS THAT THE MOST FREQUENT AND UPPER AGE LIMITS WERE 75 AND 80. AND IN ALL, SO WHILE 53% EXCLUDED SOME ELDERLY 43% OF TRIALS HAD UPPER AGE LIMITS OF 80 OR LESS. AND SO THIS IS REMARKABLE BECAUSE THIS IS NOT JUST THAT ELDERLY PATIENTS ARE BEING EXCLUDED SO THAT THERE'S AN UPPER AGE CUT OFF BUT THE AGE IS AT AGING WHICH REALLY EXCLUDES A SUBSTANTIAL PORTION OF OUR PATIENTS THAT WE ARE BOUND TO SEE IN CLINICAL PRACTICE. ALSO OF NOTE, GET BACK TO THIS IDEA OF ELIGIBILITY VERSUS ACTUAL ENROLLMENT AMONG TRIALS THAT DID NOT HAVE UPPER AGE EXCLUSIONS, 17% OF THESE STILL ENROLLED NO PATIENTS 80 YEARS OR OLDER. SO WHAT THIS SPEAKS TO IS THAT EVEN IF WE DO NOT--EVEN IF WE ELIMINATE THE EXCLUSION OF OLDER PARTICIPANTS WE NEED TO MAKE A CLOSE LOOK AT WHAT ARE THE OTHER FACTORS THAT MAY BE CONTRIBUTING TO THE UNDERREPRESENTATION BOTH IN TERMS OF ENROLLMENT AND THEIR LONG-TERM RETENTION. AND ARE WE DOING ANY BETTER OF A TIME? HERE WE'RE BREAKING THIS DOWN OVER THE STUDY DURATION FROM 2006 THROUGH 2015 THERE'S A SMALL BUT SIGNIFICANT INCREASE IN THE EXCLUSION OF ELDERLY PATIENTS. SO IN 2015, LOOKING AT THE LAST COLUMN, THERE WERE 62.4% OF THESE TRIALS THAT EXCLUDED ELDERLY PATIENTS. SO WHERE THAT DOES LEAVE US IN TERMS OF RESULTS THAT CAN BE GLEANED FROM THIS COHORT OF STUDIES? ARE THEY REPRESENTATIVE OF OUR PATIENTS AND CAN WE EXTRAPOLATE THEM FROM THE PATIENT POPULATION. THE MEAN AGE OF OUR TRIAL PARTICIPANTS WAS 2.7 YEARS SO WE CAN COMPARE THIS TO THE REAL WORLD, BASED ON SEVERAL LARGE POPULATION BASED SURVEILLANCE STUDIES. THE MEAN AGE OF INDIVIDUALS PRESENTING WITH ACUTE CORONARY SYNDROME IS 70 YEARS. SO BY EXPLICITLY EXCLIEWTING OLDER PATIENTS WE END UP WITH A TRIAL COHORT THAT IS NOT REPRESENTATIVE, AT LEAST IN TERMS OF AGE. WHAT ABOUT THE INTRIEWKS, SO THE PROPORTION OF PATIENTS WHO ARE AGE 65 AND GREATER WAS 42.5% AND THOSE AGE 75 YEARS AND OLDER WAS 12.3%. AND THIS IS HOW THIS COMPARES TO OUR ACTUAL PATIENTS. 56% OF INDIVIDUALS WITH CORONARY HEART DISEASE ARE 65 AND OLDER. AND 40% OF INDIVIDUALS HOSPITALIZED FOR ACUTE CORONARY SYNDROME ARE 75 YEARS AND OLDER. SO, CERTAINLY AT THE AGE OF 65 AND OLDER WE ARE ALREADY SEEING SOME DISCREPANCIES BETWEEN 42 AND 56%. BUT THERE'S REALLY A CLEAR UNDERREPRESENTATION OF OUR OLDEST PATIENTS THOSE 75 AND OLDER IF YOU COMPARE THE 12% ENROLLED IF TRIALS VERSUS THE 40% THAT WE'RE SEE NOTHING OUR REAL WORLD CLINIC POPULATION. THIS IS HOW THIS LOOKS ON A BOX PLOT. SO HERE WE'RE LOOKING AT THE INTRIEWKS OF THE PROPORTION OF PATIENTS AGE 65 AND OLDER AND 75 AND OLDER. SO THE MEAN NUMBER--THE MEAN PROPORTION OF PATIENTS 65 AND OLDER WAS 38 AND THE MEAN PROPORTION 75 AND OLDER WAS NINE%. THIS IS IN THE ACTUAL CLINICAL TRIALS. THIS IS WHERE WE WOULD EXPECT THAT MEAN LINE TO BE HAD WE NOT SELECTIVELY ENROLLED YOUNGER PATIENTS. AND THIS IS WHERE IT WOULD BE FOR PATIENT 75 AND OLDER SO HERE THE DISCREPANCY BETWEEN THE BLACK MEAN LINE AND THE RED LINE, THIS IS REPRESENTATION OF OUR DIRECT SELECTION OF OUR YOUNGER PATIENTS AMONG OUR PATIENT COHORTS. SO I FOCUSED HERE ON ASCHEMIC HEART DISEASE BUT CERTAINLY THESE FINDINGS HAVE BEEN SHOWN ACROSS A NUMBER OF DIFFERENT CONDITIONS. THIS IS AN EXAMPLE HERE OF A STUDY THAT WAS PUBLISHED LOOKING AT THE EXCLUSION OF OLDER ADULTS FROM ONGOING CLINICAL TRIALS ABOUT TYPE TWO DIABETES. AND THEY FOUND THAT 66% OF TRIALS EXCLUDED ELDERLY PATIENTS BASED ON ORBCONTRARY UPPER AGE LIMIT. ANOTHER STUDY HERE LOOKED AT THE ELDERLY AND UNDERREPRESENTATION IN ARTHRITIS CLINICAL TRIALS AND THEY FOCUSED ON THE AGE OF PARTICIPANTS. WHAT THEY FOUND WAS THAT THE MEAN AGE OF THEIR PARTICIPANTS WAS 63 AND THEY COMPARED THIS TO THE FINDING THAT THE MEAN AGE OF PATIENTS SEEKING TREATMENT FOR OFTIO ARTHRITIS WAS 79 YEARS SO THESE ARE TWO VERY DIFFERENT PATIENT POPULATIONS. AND JUST AS A LAST EXAMPLE, THIS IS A STUDY LOOKING AT NONSMALL CELL LUNG CANCER SO NSCLC IN THE TITLE AND THEY LOOKED AT WHETHER ELDERLY PATIENTS ARE EXCLUDED FROM THESE TRIALS AND THEY HAD TWO MAIN FINDINGS. THE FIRST WAS THAT 33% OF THE TRIALS DID IN FACT EXCLUDE ELDERLY PARTICIPANTS AND THE SECOND WAS BASED ON THE MEDIAN AGE OF THE TRIAL PARTICIPANTS VERSUS STUDIES, VERSUS THE REAL WORLD. THE DID SHE LINE AT 70 SHOWS MEDIAN AGE OF PATIENTS WITH NONSMALL CELL LUNG CANCER AND THE THEY FOUND THAT AMONG ALL STUDIES ON THIS CONDITION, THE MEDIAN AGE WAS 61. BUT THIS IS WHAT I FIND REALLY INTERESTING. IF YOU LOOK AT THE STUDIES THAT EXCLUDED THE ELDERLY VERSUS THOSE THAT DID NOT EXPLICITLY EXCLUDE THE ELDERLY, THE MEDIAN AGE IS STILL FAIRLY SIMILAR. AGAIN EXPLICIT EXCLUSION IS JUST ONE FACTOR IN THE UNDERREP REISN'TATION OF ELDERLY IN CLINICAL TRIALS. ALL RIGHT, SO ARE WE FILLING THE GAP ELSEWHERE? SO WE'RE NOT PROPERLY REPRESENTING THE ELDERLY AMONG TRIALS ACROSS ADULTS BUT ARE THERE OTHER WAYS THAT WE'RE MAKING UP FOR THIS. ONE WAY TO ADDRESS THIS MIGHT BE TO HAVE GREATER CLINICAL EVIDENCE ARE FOCUSED ARKSZ ROUND EXCLUSIVELY ELDERLY PATIENTS. SO IN THIS CASE FOR EXAMPLE, WE COULD STUDY SPECIFIC CONDITIONS THAT ARE KNOWN TO REPRESENT A LARGE BURDEN IN THELEDDERLY THELEDDERLY--ELDERLY. SO I LOOKED AT THIS ANALYSIS WITH TWO GOALS. THE FIRST WAS TO DEFINE THE PREVALENCE OF SUCH TRIALS AND SO HOW OFTEN ARE WE CONDUCTING TRIALS EXCLUSIVELY ONLEDDERLY PATIENTS AND WHEN WE ARE, WHAT IS THE ALIGNMENT BETWEEN THE DISEASE BURDEN AND THE CONDITIONS THAT WE CHOOSE TO STUDY IN THESE STUDIES. HERE I LOOKED AGAIN AT CLINICALTRIALS.GOV. THIS TIME I LOOKED AT ALL INTERVENTIONAL TRIALS THAT WAS STUDYING EXCLUSIVELY ELDERLY, THOSE 65 AND HOLDER LIMIT THOSE TO HIGH INCOME COUNTRIES AND START DATES OVER A NINE YEAR PERIOD FROM 2006 TO 2014. TO GET AT THE DISEASE BURDEN, I TURN TO THE GLOBAL BURDEN OF DISEASE 2010 STUDY. SO THIS IS A COMPREHENSIVE GLOBAL COLLABORATIVE PROJECT THAT QUANTIFIES MORTALITY AND DISABILITY REALLY RELATED TO DISEASE AND INJURIES. AND IT PROVIDES THE DISEASE MEASURE IN DISABILITY ADJUSTED LIFE JEERS OR DALYs, AND THIS IS SUITED TO THE PURPOSE BECAUSE DALYs IS A COMBINATION NOT ONLY OF YEARS OF LIFE LOST DUE TO PREMATURE DEATH BUT ALSO YEARS OF LIFE LIVED IN DISABILITY OR WITH REDUCED QUALITY OF LIFE. AND THIS IS REALLY A COMBINATION OF THE TWO IS WHAT'S NEEDED WHEN WE'RE WE THINK ABOUT RESEARCH ACTIVITY. WE WANT TO FOCUS ON BOTH MORBIDITY AND MORTALITY. SO I OBTAINED THESE FOR PERSONS 65 AND OLDER RESIDING IN HIGH INCOME COUNTRIES TO COMPARE TAKEN--THEY TO OUR RESEARCH ACTIVITY AND HERE'S WHEY FOUND SO FOR STARTERS LOOKING AT ALL INTERVENTION TRIALS STUDYING EXCLUSIVELY ELDERLY PERSONS OVERALL THERE ARE 80,965 TRIALS AND OF THOSE 11112 OR 1.4% EXCLUSIVELY STUDIED THE ELDERLY. SO THAT GETS THE FIRST QUESTION, HOW PREVALENT ARE THESE TRIALS, 1.4% ARE FOCUSED EXCLUSIVELY ON THE ELDERLY AND ON THESE TRIALS THE INTERVENTIONS STUDIES ARE PRIMARILY DRUGS ABOUT 33%, BEHAVIORIAL INTERVENTIONS AT 18%. DIETARY SUPPLEMENTS 10% 10%--PERSPECTIVE THE USUAL FEATURE THAT'S CITED IS ABOUT 60% OF INTERVENTIONAL TRIALS ARE FUNDED BY INDUSTRY. SO THIS IS CERTAINLY MUCH LESS AT 19%. SO NOW THINKING ABOUT THE DISEASE BURDEN THAT WHERE WE--THAT WE NEED MOST FOR THESE PATIENTS WHAT ARE THE CONDITIONS THAT WERE STUDIED. HERE WE'RE LOOKING AT THE 10 MOST FREQUENTLY STUDIED CONDITIONS BASED ON THE NUMBER OF TRIALS. SO THERE'S ALZHEIMER'S DISEASE, DEMENTIA, FALLS, MUSK LO SKELETAL DISORDERS, LOWER RESPIRATORY INFECTIONS, INJURIES BEING LUNG CANCER, DIABETES LEUKEMIA AND OTHER CANCERS. SO THESE ARE THE CONDITIONS MOST FREQUENTLY STUDIED IN THIS POPULATION AND ONE APPROACH THAT'S BEEN TAKEN TO LOOK AT THE ALIGNMENT BETWEEN RESEARCH ACTIVITY ACTUAL DISEASE BURDEN AND DALYs PER TRIAL. SO IN THIS CASE YOU'RE LOOKING AT HOW MUCH DISEASE BURDEN AND COVERED BY EVERY TRIAL AND THAT'S WHAT YOU'RE LOOKING AT IN THE FOREMOST COLORADO UMKC AND SO FOR EXAMPLE, LOOK AT LUNG CANCER AND LEUKEMIA, THE NUMBER TRIALS HERE ARE 36 AND 33, AND THE NUMBER OF DALYs IN 4.6733000 MILLION. SO WHILE THERE'S A VERY SIMILAR NUMBER OF TRIALS THERE'S THE DISEASE BURDEN IS DIFFERENT AND THIS YEELDS A VERY DIFFERENT DALYs PER TRIAL. SO THIS IS 222,000 FOR LEUKEMIA SO THIS SHOWS THAT IT'S COMPARATIVELY UNDERREPRESENTED TO LEUKEMIA. ONE THING TO NOTE IN LOOKING AT THE COLUMN IS THE VARIATION IN THE NUMBER. EVEN 2230. SO HOW DOES THIS LOOK ACROSS ALL THE CONDITIONS THERE ARE ABOUT 150 OF THEM. IN THIS FIGURE, WE HAVE ALL THE DIFFERENT CONDITIONS ALONG THE X-AXIS AND DALYs PER TRIAL AND YOU CAN SEE OVERALL THERE'S TREMENDOUS VARIATION IN THE RANGE OF 325 TO 1.6 MILLION DALYs PER TRIAL. WHICH REPRESENTS A GREATER THAN 5000 FOLD PER RANGE. SO WHAT THIS INDICATES IS THAT IN ALLOICATING OUR RERESEARCH ACTIVITY CERTAINLY THE BURDEN OF DISEASE IS NOT THE FOREMOST FACTOR. THERE ARE OTHER DETERMINANTS OF WHAT WE CHOOSE TO STUDY. NOT SURPRISINGLY THE CORRELATION WAS MODERATE SO, A SPEAR MAN CORRELATION FACTOR WAS 0.5 BETWEEN RESEARCH ACTIVITY AND DISEASE BURDEN. SO THIS WAS DALYs PER TRIAL. ANOTHER WAY TO LOOK AT IT IS THIS RAPPED ORDER OF MICRONSIZED PARTICIPANTS. SO THIS WOULD TAKE INTO ACCOUNT THAT SOME TILES SIMPLY HAVE A MUCH LARGER NUMBER OF PARTICIPANTS, LARGER SAMPLE SIZE, WHERE OTHERS WOULD HAVE A SMALLER NUMBER OF PARTICIPANTS. BUT AGAIN YOU SEE TREMENDOUS DISTRIBUTION ACROSS THE DIFFERENT CONDIGDZS FOR DALYs RANDOMIZED PARTICIPANT AND THE CORRELATION WAS LOWER HERE AT 0.3. SO WE NEED ACTIONABLE INFORMATION FROM THIS AND ONE WAY TO SLIDE THIS IS TO LOOK AT THE DISEASE CATEGORY THAT WERE MOST UNDERREPRESENTED AND AT THIS TABLE WE'RE LOOKING AT THE 10 DISEASES THAT WERE MOST UNDERREPRESENTED IN TERMS OF DALLY'S PER TRIAL AND THESE WERE COPD STROKE, ASCHEMIC HEART DISEASE AND LOW BACK AND NECK PAIN AND STOMACH CANCERS AND HYPER TENSIVE HEART DISEASE AND PROSTATE CANCER AND SKIN AND ANOTHER THENG I WOULD LIKE YOU TO NOTE IN LOOKING AT THIS IS INLET FIRST COMUMKC I'VE INCLUDED DISEASE BURDEN RANK SO ACCORDING TO THE DID, ALYs, WHAT WAS THE RANK OR DISEASE BURRED KNOW FOR THESE PATIENTS. AND YOU CAN SEE THAT AMONG THE TOP FOUR UNDERREPRESENTED CONDITIONS THESE ARE ALL IN THE TOP 10 ALSO IN TERMS OF DISEASE BURDEN. IN FACT, ASCHEMIC HEART DISEASE AND STROKE ARE THE TWO CONDITIONS THAT REPRESENT THE GREATEST DISEASE BURDEN AMONG ELDERLY PATIENTS BUT THEY'RE ALSO THE MOST UNDERREPRESENTED. SO AGAIN WE'RE NOT LOOKING AT THE NEEDS EVER THE ELDERLY PATIENTS NECESSARILY WHEN MAKING OUR DECISIONS AROUND THE ALLOCATIONS OF RESOURCES AND STUDIES. TAKING THIS ONE STEP FURTHER I DECIDED TO ELECTRIC AT THE DISEASE CATEGORIES THAT ARE MOST--PRIMARILY PREVALENT AMONG THE ELDERLY, SO THOSE WITH 80% OR MORE OF THE DISEASE BURDEN AMONG ELDERLY PERSONS. AND THE FIVE HERE, ALDZ HYMER'S DISEASE, PARKINSON'S DISEASE, PROSTATE CANCER ATRIOLE FIB ROUGH ATOM LAIGDZ AND PERIPHERAL VASCULAR DISEASE THEY ALL HAVE 80-91% AMONG ELDERLY PATIENTS. FOR ALZHEIMER'S DISEASE WE'RE DOING PRETTY WELL. 96 TRIALS ARE STUDYING ALZHEIMER'S DISEASE EXCLUSIVELY IN THE ELDERLY BUT LOOK AT THE OTHER ONES. ZERO, FIVE, 11, FIVE. THE NUMBER OF TRIALS FOR THESE CONDITIONS THAT EFFECT PRIMARILY ELDERLY PATIENTS. SO BEFORE CLOSING, I JUST WANT TO HIGHLIGHT A FEW INDICATORS THAT THERE IS ACTUALLY ROOM TO MOVE. SO RESEARCHERS HAS SHOWN THAT WHEN APPROACHED OLDER PATIENTS ORLEDDER ADULTS OFTEN WILLING TO PARTICIPATE IN CLINICAL RESEARCH AND EXPERIENCE INVESTIGATORS HAVE ALS DEVISED STRATEGIES AND TECHNIQUES TO DESCREASES SOME OF THESE CHALLENGES AND BARRIERS IN ORDER TO ENROLL PARTICIPANTS AND RETAIN THEM IN STUDIES AND THEY POINT TO A NUMBER OF KEY APPROACHES IN DOING SO. FIRST THE EARLY AND INDEPTH PLANNING ABOUT HOW TO ENROLL PATIENTS AND RETAIN THEM, THE NEED TO MINIMIZE EXCLUSION CRITERIA AND THE IMPORTANCE OF USING ADVOICERY BOARDS TO IDENTIFY APPROPRIATE PATIENT COHORTS. THE CAREFUL REVIEW OF BENEFIT RISK VATIOS AND ALSO THE NEED TO HAVE DETAILED STRATEGIES FOR HOW TO RETAIN THESE PATIENTS OVER TIME THROUGH THE COMPLETION OF A TRIAL. SO IN SUMMARY, IN TERMS OF EXCLUSION OF ELDERY PATIENTS EVEN FOR DISEASES THAT EFFECT MOST THE ELDERLY, MANY CLINICAL TRIALS DO EXCLUDE ELDERLY PATIENTS SPECIFICALLY BASED ON PATIENT AGE AND DEFINITELY OTHER INDIRECTION EXCLUSION FACTORS THAT APPEAR TO BE AT PLAY AND WE NEED TO CONSIDER. ULTIMATELY THE ENROLLED PARTICIPANTS ARE NOT REPRESENTATIVE OF REAL WORLD POPULATIONS AND WE'RE NOT NECESSARILY COMPENSATING FOR THIS WITH THOSE THAT ARE CONDUCTED EXCLUSIVELY IN THELEDDERLY AND VERY SUCH STUDIES ARE CONDUCTED AND WHEN THEY ARE, THE CONDITIONS THAT ARE STUDIED ARE POORLY ALIGNED WITH ACTUAL DISEASE BURDEN IN THE ELDERLY. THANK YOU VERY MUCH. [ APPLAUSE ] ANY QUESTIONS? SNRKTS I'M ARMONY REYNOLDS FROM NEW YORK UNIVERSITY, I WOULD LIKE TO POINT OUT THAT AN EXCLUSION FACTOR IN THE ELDERLY IS AGE, IT'S PART OF THE CALCULATION AND IT'S QUITE REASONABLE IN THE ANTITHROMBOTTIC STUDY THAT SOY THAT THOSE MIGHT BE A RISKER FACTOR FOR BLEEDING AND OF COURSE WE NEED THAT INFORMATION BUT THAT MAY BE PART OF THE REASON FOR INDIRECT EXCLUSION. >> I THINK YOU'RE ABSOLUTELY RIGHT AND I THINK THAT A NEXT STEP FOR A NUMBER OF THESE ANALYSIS WILL BE TO LOOK AT THE SPECIFIC JUSTIFIED OR UNJUSTIFIED EXCLUSION FOR THE ELDERLY, CERTAINLY THERE ARE CERTAIN INTERVENTIONS FOR WHICH YOU WOULD HAVE REASONS TO EXCLUDE CERTAIN ELDERLY POPULATIONS. >> MY NAME IS NAM NGYUN, WE'RE I AM A RADIOLOGYST AT HOWARD UNIVERSITY. WE HAVE INTERNATIONAL RESEARCH ON THE ELDERLY PRACTICE CALLED [INDISCERNIBLE], IT'S VERY DIFFICULT TO FIND FUNDING OR INDUSTRY OR FOR KD--SALLIA FOR ELDERLY CANCER PATIENT. ABOUT FOUR YEARS AGO WE APPLIED FOR A GRANT FOR BREAST CANCER IN THE ELDERLY, AND THESE ARE OLDER AND THEN WE TRY TO COMPARE SIX WEEKS OF RADIATION FOR BREAST CANCER AND COMBINE ONE WEEK AND QUALITY OF LIFE. WE APPLY FOR THE GRANT, IT WAS REJECTED WITHOUT ANY COMMENT. SO THAT'S WHY THE DIFFICULTY--WE HAVE NO PROBLEM RECRUIT PATIENT BECAUSE WE HAVE OVER 100 INSTITUTIONS, IN 50 COUNTRY IN THE WORLD SO WE HAVE NO PROBLEM--MINORITY WE HAVE ASIA, AFRICA, EUROPE, AND WE HAVE ABOUT 10,000 CANCER PATIENTS IN THE RESEARCH CONSORTIUM BUT IT'S VERY DIFFICULT TO FIND FUNDING. THAT'S THE MAJOR CHALLENGE OF THIS. >> AND YEAH, AND CERTAINLY ALONG THOSE LINES INDUSTRY FUNDING IS A BIG COMPONENT OF TRIALS AND WHAT WE FOUND WAS THAT THEY ARE NOT A BIG--AS BIG A FUNDER FOR THESE ELDERLY STUDIES. >> HI, I'M CYNTHIA BOYD FROM JOHNS HOPKINS AND REALLY ENJOYED YOUR TALK. EGFR AS BEING ONE OF THE MANY REASON--ONE OF THE MAIN REASONS THAT OLDER PEOPLE MAY NOT END UP INCLUDED. I THINK THERE ARE--AT A BROADER LIST OF CO-MORBIDITIES AS DR. HODUS AND DR. COLLINS MENTIONED IN EARLIER PRIOR WORK HAS SHOWN FOR EXAMPLE AT THE SAME TIME THAT AGE EXCLUSIONS WERE GOING AWAY FOR CLINICAL TRIALS FOR HEART FAILURE, THE NUMBER OF EXCLUSIONS FOR MAJOR CO MORBIDITIES THAT ARE ACTUALLY REALLY VERY COMMON IN PEOPLE WITH HEART FAILURE WAS ACTUALLY INCREASING SO I THINK THIS QUESTION OF WHAT'S A JUSTIFIABLE EXCLUSION AND WHAT ISN'T AND WHAT THAT ENDS UP MEANING FOR THE REPRESENTATIVE OF THE POPULATION THAT WE END UP TREATING IS REALLY AN IMPORTANT THING TO KEEP ON OUR TO DO LIST. >> IF WE DO HAVE TO EXCLUDE THEM THEN PERHAPS IDENTIFYING THE EFFORTS THAT NEED TO MATCHUP BETWEEN OUR YOUNGER TRIAL POPULATION VERSUS ACTUAL PATIENT POPULATION. >> GOOD AFTERNOON. JAMES APPLEBY, THE GERIATRICKIZATIONON TO LOGICAL SOCIETY OF AMERICA. WONDERING IF UPON YOUR RESEARCH WHAT NUMBER IF ANY ARE YOU TRYING TO COME UP WITH MORE OF A FUNCTIONAL MEASUREMENTS OF AGE VERSUS PURLY CHRONOLOGICAL--THINKING ABOUT THE ENORMOUS HETEROGENEITY IN THE OLDER ADULT POPULATION. IT SEEMS TO ME THAT THAT THE AGE IN SOME WAYS TAKES US DOWN A PATH THAT PERHAPS WON'T BE AS VALUABLE GOING FORWARD WITH MORE OLDER ADULTS AND AGAIN MORE HETEROGENEITY, IS FUNCTIONAL STATUS SOMETHING THAT'S EMERGING OR SOMETHING YOU CAME ACROSS IN YOUR WORK OR SOMETHING BEING STUDIED? >> IT'S I GREAT POINT. IT'S NOT SOMETHING I LOOKED AT. I LOOKED AT THE PURE EXCLUSION BASED ON AGE BUT EXCLUSION BASED ON THESE OTHER FUNCTIONAL CRITERIA YOU MENTION ARE PROBABLY AT PLAY AS WELL. >> MARSHA FROM STANFORD, I THINK THE ISSUE YOU BRENG UP ABOUT EVEN IF YOU DON'T HAVE AN EXCLUSION, YOU DON'T BRING PEOPLE IN, I WAS FROM THE WOMAN'S HEALTH INITIATIVE AND WE REALLY HAD AGE CRITERIA WHERE WE WERE REALLY TARGETING DECADES SO WE CLOSED THE CELLS TO YOUNGER POOEM AND THEN MOVED IT UP SO WE COULD GET OLDER WOMEN AND SO I THINK IN TERMS OF TRYING TO FIGURE OUT HOW YOU NEED TO DO THAT, WE NEED TO BE THINKING ABOUT GRANTS WHERE YOU HAVE TO TRY AND GET 30% OF YOUR POPULATION IN THAT AGE GROUP SO THAT YOU REALLY ARE TARGETING SPECIFIC CRITERIA AND SHUTTING DOWN THE RECRUITMENT TO YOUNGER PEOPLE AND I AM SURE WE WILL OLDER POPULATION WE'RE TALKING ABOUT IS VERY OVERREPRESENTED BY WOMEN AND SO I'M REALLY EAGER TO HEAR HOW WE'RE GOING TO TALK ABOUT THAT ISSUE. >> ROGER FROM THE UNIVERSITY OF VERMONT. AS A FELLOW PEDIATRICIAN, I WOULD LOVE TO HEAR MORE ABOUT THIS IN OUR AGE GROUPS BUT IT WAS A WONDERFUL TALK. I WONDER THERE WAS A BROADY QUER OR FOCUS NOT NECESSARILY WRONG ON EFFICACY TRIALS AS OPPOSE TO EFFECTIVENESS TRIAL WHERE WE ARE SEEKING A POSSIBLE POSITIVE EFFECT. THAT'S IMPORTANT. WE HAVE TO TAKE THAT FIRST STEP. THE FACT WE IGNORE THE EFFECTIVENESS IN BROAD POPULATIONS NOT JUST ELDERLY BUT CERTAINLY IN ALL AGES. >> YEAH, THANK YOU FOR THAT. I THINK THAT'S--OBVIOUSLY THAT'S NOT SOMETHING WE ARE ABLE TO LOOK AT BUT BEING ABLE TO SUBCATEGORIZE THAT FURTHER WOULD BE INFORMATIVE. >> GOOD AFTERNOON, [INDISCERNIBLE] FROM THE MALFI CENTER IN TAMPA I WOULD LIKE TO SAY THREE THINGS THAT MAY BE CONCERNING THE WORKING GROUP LATER ON, NUMBER ONE, I WANT TO ECHO WHAT THE COLLEAGUE, THAT THE RADIATION ONCOLOGIST SAYS, IT'S VERY DIFFICULT TO HAVE GRANTS APPROVED BY THE INSTITUTIONS BECAUSE THE EXPERTISE IS A FIELD OF AGING OUTSIDE OF NIA IS VERY LITTLE ESPECIALLY IN THE CANCER EN--STRATEGIESITUTE SO I THINK THAT IS ONE ISSUE THAT IF WE'RE SERIOUS ABOUT ENCLUEDING OLDER PEOPLE IN CLINICAL TRIALS, THE ISSUE NEEDS TO BE ADDRESSED FIRST. SECOND, I WANT TO BUILD ON WHAT WAS SAID ABOUT THE FUNCTIONAL ASSESSMENT OF AGING. IF WE ARE SERIOUS ABOUT HAVING--ABOUT HAVING OLDER INDIVIDUALS INCLUDED IN CLINICAL TRIALS, I THINK IT'S ESSENTIAL THAT WE SOMEHOW HAVE A HOMOGENIUS CONSENSUAL DEFINITION OF PHYSIOLOGICAL AGE. LET'S SAY BREAST CANCER PATIENT 90 YEAR-OLD IN CLINICAL TRIAL, MAY NOT BE REASONABLE BECAUSE THAT PATIENT MAY NEVER BY OF BREAST CANCER AND MAY NEVER SUFFER CONSEQUENCES OF BREAST CANCER-- >> YEAH, I UNDERSTAND. >> BUT I'M--THAT WOMAN HAS A LIFE EXPECTANCY OF TWO YEARS F. SHE HAS A LIFE EXPECTANCY OF 20 YEARS, CLEARLY SHE SHOULD BE INCLUDED IN THE CLINICAL TRIAL. AND THIRD, THAT I DON'T KNOW IF IT IS A LITTLE OUT OF THE MANDATE OF THIS SYMPOSIUM, THIS WORKSHOP, BUT, I'M WONDERING IF THE CLASSICAL CLINICAL TRIALS ARE INDEED THE BEST WAY TO GET INFORMATION ON OTHER INDIVIDUALS. AND THE COLLEAGUE MENTIONED THE STUDY OF EFFICACY INSTEAD OF EFFECTIVENESS BUT AGAIN THAT IS AN ISSUE IN MY OPINION TO LOOK MORE ON DATABASES, SO CALLED RAPID LEARNING DATABASES, RATHER THAN TO LOOK AT PHASE TWO CLINICAL--THREE CLINICAL TRIALS, AS THE CENTER OF PUBLICATIONS SAY THAT THE EVIDENCE-BASED MEDICINE IN GERIATRICS IS [INDISCERNIBLE] BIAS MEDICINE. >> GREAT POINTS FOR OUR WORKING GROUPS FOR SURE. >> HI, LEAH, WITH CHILDREN'S HOSPITAL. I GUESS FUNDAMENTALLY ONE OF THE QUESTIONS IS WHAT DO WE KNOW ABOUT BEHAVIOR AND EDUCATION AND TRAINING OF THE CLINICAL TRIALISTS WHO ARE WRITING THESE DESIGNs AS WE THINK ABOUT WHY DO WE SET UPPER AGE LIMITS AND WHAT THOUGHT PROCESS GOES INTO THE DETERMINE NATION OF AN UPPER AGE LIMIT IN A CLINICAL TRIAL. AND IS THAT SORT OF JUST A DEFAULT, AN AFTERTHOUGHT, SORT OF WHAT DOES THAT DECISION MAKING PROCESS LOOK LIKE FOR ACTUAL INVESTIGATORS. SO WE CAN'T EFFECT THE PATIENTS ON TRIAL UNTIL THE INVESTIGATORS CHANGE THEIR BEHAVIOR, RIGHT? >> RIGHT. >> WHAT DO WE KNOW ABOUT THOSE DECISIONS ARE MADE? HOW DO YOU DECIDE, 65, 75, 90, NO UPPER AGE LIMIT AND HOW DO WE EVALUATE THE DEITION MAKING PROCESS IN GRANT APPLICATIONS BUT THEN IN CLINICAL TRIALS. WADO WE KNOW? >> IT'S A GREAT POINT. I THINK IT ALSO GETSA THE FACT THAT THERE MAY BE JUSTIFIED AND UPPER JUSTIFIED SCIENTIFIC AGE LIMITS. SOME MAY BE SCIENTIFICALLY SOUND. >> JIM GRIFFIN FROM NICHD, THANK YOU FOR A WONDERFUL PRESENTATION. ONE THING I WANT TO UNDERSCORE UNLIKE DR. BIANCI'S PRESENTATION, YOU INCLUDED ALL CLINICAL TRIALS BY INDUSTRY, INCLUDING ONE OF THE THINGS THAT WAS EXCLUSION CRITERIA, 2012 WHEN WE STARTED REQUIRING REGISTRATION OF CLINICAL TRIALS AND THEN YOU SAW AN INCREASE OF NUMBER OF INCLUSION CRITERIA AND INCREASED NUMBER SO ONE OF THE--SO ONE OF THE THINGS I WANT TO ASK THOUGH IS IF YOU HAVE ANY OBSERVATIONS OF ANY DIFFERENCES YOU MIGHT HAVE SEEN ON TRIALS FUNDED BY NIH VERSUS INDUSTRY BY OTHER SOURCES. >> I DIDN'T ACTUALLY ENCLUED THAT SLIDE BUT THE EXCLUSION FOR--IF YOU LIMIT TO NIH FUNDED TRIALS, THE EXCLUSION IS LESS FOR ELDERLY AND FOR CHILDREN OVERALL. >> MICKEY FROM DUKE UNIVERSITY. SO FLORENCE, I WONDER IF YOU HAVE HAD AN OPPORTUNITY TO ALSO LOOK AT THE EARLY PHASE STUDIES, YOU KNOW EVEN IF WE WERE TO INCLUDE ELDERLY IN PHASE THREE OR EFFECTIVENESS STUDY, WE OFTEN DON'T EVEN KNOW WHAT DOSE THEY SHOULD BE GIVEN BECAUSE THEY WERE ORIGINALLY EXCLUDED FROM THE EARLY PHASE STUDIES SO THERE ARE PLANS TO DO SUBANALYSIS AND THOSE EARLIER TRIALS TO SEE IF THERE ARE AREA BEING INCLUDED EARLY ON? >> YEAH, THAT'S A GREAT POINT. I HAVEN'T DONE THAT, IT CAN BE DONE, I THINK THAT MOST OF THE TRIALS THAT WERE INCLUDED HERE WERE CERTAINLY PHASE THREE TRIALS. ALSO, THE ISSUES AROUND THE INCLUSION, EXCLUSION IN EARLIER TRIALS MAY BE DIFFERENT BUT STILL CERTAINLY WORTH EXPLORING. >> SAMIR, FROM THE NIA'S PLANNING OFFICE. I WANT TO SAY YOU'VE DONE A GREAT JOB AND NIA HAS DONE ITS OWN ANALYSIS OF ENCLIEWGZ AND EXCLUSION OF CRITERIA FOR OLDER ADULTS AND PHASE THREE STUDIES AND THEN WE WILL BE PUSHLISHING DATA AT SOME POINT. SO WE WILL ADD TO WHAT YOU ALREADY SHARED WITH US. >> WONDERFUL. [ APPLAUSE ] . >> GOOD AFTERNOON I'M GOING TO SHIFT GEARS A LITTLE BIT AND TALK A BIT ABOUT A TOPIC THAT'S RELATED BUT SLIGHTLY DIFFERENT AND I WANTED TO CHAIRVELG MY TITLE BUT MY STAFF WILL KILL ME IF I MAKE A LAUGH MINUTE CHANGE TO IT BUT I WILL SAY THE TITLE REALLY IS GOING BEYOND INCLUSION, WOMEN AND CLINICAL TRIALS. OKAY? I ALWAYS LIKE TO BEGIN ALL OF MY PRESENTATIONS BY HONORING THE LEGACY OF THIS OFFICE. IT'S A VERY UNUSUAL OFFICE AND AS YOU KNOW THE MISSION OF THE OFFICE IS TO EXPAND WOMEN'S HEALTH RESEARCH CONDUCTED AT NIH BUT THIS OFFICE WAS FOUNDED OUT OF THE ISSUE THAT WOMEN WERE NOT BEING SYSTEMATICALLY INCLUDED IN CLINICAL TRIALS THAT WERE BEING CONDUCTED AND THE EVIDENCE FROM THOSE TRIALS WAS BEING APPLIED TO WOMEN WITHOUT UNDERSTANDING WHETHER THAT INFORMATION WAS VALID FOR WOMEN. YOU DON'T ALWAYS HEAR THE AND. SO, THAT'S--I WANT TO KEEP THE FULL PICTURE HERE. OF COURSE, WE ALSO ARE ATTENDING TO PROMOTE WOMEN'S STEM AND YOU WILL HEAR LATER ABOUT OTHER TOPICS THAT WERE HIGHLIGHTED BEFORE. SO HERE'S MY UT LINE. I AM--OUTLINE. I WILL TALK GENERALLY ABOUT HOW WE'RE DOING OVERALL WITH WOMEN IN CLINICAL TRIALS. I WILL CHALLENGE YOU IN TERMS OF HOW INCLUSION SHOULD FIT INTO THE CLINICAL RESEARCH PROCESS AKIN TO THE PROCESS THAT WERE JUST ASKED ABOUT THAT, WHERE ARE WE--PEOPLE THINKING ABOUT IT, HOW DO WE KNOW THEY THOUGHT ABOUT IT AND IN TUNE WITH THE THEME OF THIS WORKSHOP, I WILL TALK ABOUT SEX AND GENDER INFLUENCES ON DISEASE ACROSS THE LIFE SPAN, AND IMPLICATIONS FOR THE CLINICAL RESEARCH PROCESS AND END WITH SOME RESOURCES. SO YOU'VE SEEN A LOT OF THESE SLIDES AT THIS POINT BUT THIS IS ENROLLMENT IN NIH DEFINED PHASE THREE CLINICAL TRIALS BY SEX, EXCLUDING SEX-SPECIFIC STUDIES. OKAY? SO YOU CAN SEE THAT OVERTIME, IT'S ROUGHLY--IT'S THE SAME AND IT'S MORE WOMEN THAN MEN ACTUALLY GREATER THAN 50% OF THE PARTICIPANTS IN NIH PHASE THREE FUNDED CLINICAL TRIALS IN AGGREGATE ARE WOMEN AND THAT HASN'T CHANGED FOR SOMETIME. BUT ENROLLMENT TRENDS AS YOU'VE BEEN HEARING DON'T TELL THE WHOLE STORY AND HERE'S DATA WHERE THE UNITED STATES IS COMPARED TO 21 HIGH INCOME COUNTRIES. THESE GRAFS ARE THE LIKELIHOOD TO SURVIVE THE AGE OF 50. THE UNITED STATES IS IN RED. WE ARE AT THE BOTTOM OF THE GRAPH OF THE DISTRIBUTION FOR BOTH MEN AND WOMEN AND WE HAVE BEEN FOR SOMETIME AND THE GAP IS WIDENING BETWEEN THE U.S. AND THE BEST PERFORMING COUNTRY. BUT WHAT'S REALLY DESERVING TO ME ARE THESE DOTS. WOMEN ARE LITERALLY FALLING OFF THIS CURVE. LIKELIHOOD TO SURVIVE TO THE AGE OF 50. HERE'S ANOTHER PIECE OF INFORMATION THAT I WOULD LIKE TO SHARE WITH YOU. JUST TO ORIENT YOU. THIS IS MORTALITY RATES. OVER A 10 YEAR PERIOD, IT'S DIVIDED BY COUNTY AND STATE. HERE'S THE DATA FOR MEN. THE COBALT BLUE ARE MORTALITY AND REDUCTION RATE. TURQUOISE IS MINIMAL IMPROVEMENT AND THE RED IS WORSENING. SO IN FOUR% OF COUNTIES, OVER THIS 10 YEAR PERIOD THE MORTALITY RATES ROSE FOR MEN. THIS IS THE DATA FOR WOMEN. THE MORTALITY RATES ROSE FOR WOMEN 42.6% OF COUNTIES IT THE UNITED STATES OVER THIS 10 YEAR PERIOD. SO TODAY WE'RE FOCUSING ON THIS CENTER DOT, THIS--THERE WE GO, CLINICAL RESEARCH AND CLINICAL TRIALS. ABOUT YOU I WANT TO MAKE SURE THAT WE THINK ABOUT ABOUT THE WHOLE RESEARCH CONCONTINUUM AND HOW, THERE WAS A QUESTION ABOUT THIS EARLIER, HOW THIS PIECE FITS INTO THE ENTIRE CONTINUUM FROM THE MOST BASIC RESEARCH THAT PRECLINICAL SPACE WHERE WE'RE MODELING HUMAN DISEASE, ALL THE WAY THROUGH TO CLINICAL PRACTICE WHERE OUR GOAL IS OPTIMAL HEALTH FOR EVERYONE AT EVERY AGE AND EVERY STAGE. SO THIS HAS TO BE CONNECTED FOR US TO DO THE JOB THAT WE'RE INTENDED. FOR US TO ACHIEVE OUR MISSION OF TURNING DISCOVERY INTO HEALTH. THIS HAS TO BE CONNECTED. SO HOW SHOULD INCLUSION FIT IN THE CLINICAL RESEARCH PROCESS. FIRST, I THINK IT BEGINS EVEN BEFORE THIS BUT I WILL START WITH SELECTING THE RESEARCH QUESTION. SOMEBODY CHOOSES TO STUDY CAN HAVE INHERENT DIFFERENCES RELEVANT FOR MEN AND WOMEN, OR ACROSS THE LIFE SPAN, OLDER INDIVIDUALS OR YOUNGER. AND I WON'T READ ALL OF THESE, BUT I WILL HIGHLIGHT A COUPLE THAT I WILL GIVE EXAMPLES TOO. SO DESIGNING THE STUDY WITH INCLUSION IN MIND AND YOU'VE HEARD ABOUT SOME OF THE THINGS THAT HAVE BEEN HIGHLIGHTED ALREADY WITH AGE, BUT THERE ARE OTHER EXCLUSION CRITERIA, THAT UNINTENDEDLY EXCLUDE WOMEN UNWITTINGLY SOMETIMES BECAUSE OF AN AGE GAP AND DIAGNOSIS DOESN'T APPEAR IN WOMEN UNTIL THEY'RE OVER THAT AGE OF THE AGE CAP, ANALYZING DATA WITH INCLUSION IN MIND MAKING SURE THEY'RE AGGREGATED BY SEX AND GENDER AND TRANSFERRING THAT KNOWLEDGE IN A SEX-GENDER SPECIFIC BAY AND THEN OF COURSE OUR INTENDED GOAL, MODIFYING POLICIES AND HAVING THE CLINICAL CARE REACH EACH AND EVERY ONE OF US AND OUR FAMILIES SO THAT PEOPLE GET SEX AND GENDER APPROPRIATE EVIDENCE-BASED MANAGE CARE. SO I'M FOCUSING ON SEX AND GENDER AND YOU WILL HEAR FROM DR. ELIO A BIT ABOUT RESEARCH NECESSITY AND OF COURSE WE'RE ADDRESSING THE CONTINUUM OF AIMING AND I THINK THAT WE HAVE NOT DONE A GOOD ENOUGH JOB AT LOOKING AT THE INTERSECTION OF THESE BIOLOGICAL FACTORS OF SEX AND AGE IN THAT SENSE BUT THE INTERSECTION OF THESE FACTORS THAT EFFECT HEALTH. IN TERMS OF THE DESIGN OF OUR STUDIES, ANALYSIS OF RESULTS, THE REPORTING OF THE ARE ARE--RESULTS AND THE TRANSFER OF THAT KNOWLEDGE TO CLINICAL CARE. SO IN LINE WITH THE THEME OF TODAY'S WORKSHOP I'M CHOOSING A LIFE COURSE APPROACH FOR WOMEN AND WE KNOW THAT IN CHILDHOOD, THEIR GENDER DIFFERENCES IN MANY DISEASES AND I WILL USE TWO HERE, AUTISM SPECTRUM DISORDER AND ASTHMA. AND AUTISM IS ABOUT FIVE TIMES MORE COMMON IN BOYS AND GIRLS AND WE KNOW THAT BUT WHY IS THAT IMPORTANT IN THE CONTEXT OF CLINICAL TRIALS. GIRLS ARE LESS LIKELY TO BE DIAGNOSED EVEN WHEN THEIR SYMPTOMS ARE SEVERE AND GIRLS WITH HIGHLY FUNCTIONING AUTISM SPECTRUM DISORDER ARE GENERALLY DIAGNOSED LATER THAN BOYS. IN TERMS OF ASTHMA, ASTHMA EFFECTS MORE BOYS BEFORE PUBERTY BUT MORE WOMEN IN ADULTHOOD AND THAT SWITCH IN PREVALENCE MAY BE DUE TO A VARIETY OF FACTORS. WHAT ARE THE IMPLICATIONS OF THESE DIFFERENCES? SO FOR AUTISM SPECTRUM DISORDER GIRLS WITH AUTISM SPECTRUM DISORDER MAY TEND TO BE OMIT FRIDAY CLINICAL TRIALS BECAUSE THEY'RE NOT ASCERTAINED BECAUSE THEY'RE NOT DIAGNOSED. SOME OF THE INSTRUMENTS DO LESS WELL IN DETECTING GIRLS WITH AUTISM. WE HAVE TO THINK ABOUT THE CLINICAL CRITERIA, WHAT TOOLS WE RUES FOR SCREENING AND TAYLOR THEM APPROPRIATELY TO AVOID OMITTING CERTAIN POPULATIONS AT RISK. WHAT ARE THE IMPLICATIONS IN THE ASTHMA SPACE. STRATIFICATION BY SEX, SHOULD BE CONSIDERED DURING DESIGN AND ANALYSIS. ANALYSIS SHOULD LOOK FOR INTERACTIONS SPECIFICALLY BETWEEN AGE AND SEX GENDER BECAUSE OF THE ISSUES THERE. AND TRIALS MAY WARRANT EMPHASIS ON RECRUITMENT OF AGES AROUND THOSE SWITCH POINTS. SO THESE ARE THINGS THAT NEED TO BE THOUGHT ABOUT AS THE TRIAL IS BEING DESIGN SO THE IMPLICATIONS ARE IN THE DESIGN SPACE AND THE ANALYSIS SPACE FOR CLINICAL TRIALS. THERE ARE SEVERAL COMPLICATIONS OF PREGNANCY THAT ARE STRONG REDICTORS OF LATER DISEASE. PREECLAMPIA IN SPECIFIC IS A RISK FACTOR FOR LATER CARDIOVASCULAR DISEASE AND STROKE LATER AS WELL OF COURSE DURING PREGNANCY. JESTITIONAL DIABETES INCREASES THE RISK OF SUBSEQUENT DEVELOPMENT OF TYPE TWO DIABETES. SO WHAT ARE THE IMPLICATIONS. STUDY DESIGNS NEEDS TO CAREFULLY CONSIDER WHICH DATA TO COLLECT AND HOW TO CARRY OUT A STUDY FOR EXAMPLE YOU MIGHT BE ASCERTAINING 75 YEAR-OLD WOMEN FOR A STUDY OF STROKE, YOU NEED TO ASK A PREGNANCY HISTORY. RIGHT? THOSE WOMEN WHO HAD PREECLAMPSIA 50 YEARS AGO ARE AT INCREASED RISK FOR STROKE. THEY MAY BE DIFFERENT THAN THE OTHER WOMEN IN THE STUDY. SO DESIGN IS AN IMPLICATION AS WELL AS TRANSFER OF KNOWLEDGE AND CLINICAL CARE BECAUSE AS A CLINICIAN, THAT SHOULD RAISE YOUR SUSPICION AND YOU MAY BE MORE AGGRESSIVE IN TREATING THAT 75 YEAR-OLD WOMEN OF HYPER TENSION, NOW SHE'S ON TWO MEDICATION FIST YOU KNOW SHE HAD A BRIEF HISTORY OF PREECLAMPSIA BECAUSE SHE'S AT HIGHER RISK. WHAT ABOUT GENDER DIFFERENCES IN STROKE. PREMENOPAUSAL WOMEN TEND TO HAVE FEWER STROKES THAN MEN OF THE SAME AGE BUT WOMEN HAVE MORE STROKES OVERALL DUE TO LONGER LIFE EXPECTANCY AND HIGHER INCIDENCES OF WOMEN AS COMPARED TO MEN AT OLDER AGES. THE PATTERN OF STROKE IS NOT THAT DIFFERENT ALTHOUGH THERE IS SOME SUGGESTED THAT A SIMPLE HEMORRHAGE PATTERN IS MORE COMMON IN WOMEN THAN IN MEN BUT WHEY WANT TO DRAW YOUR ATTENTION TO IS BOTH THE QUALITY OF LIFE AND FUNCTIONAL OUTCOMES ARE POORER IN WOMEN THAN MEN. SO THAT MIGHT BE IMPORTANT FOR AS AN END POINT IF WE'RE MEASURING THOSE OUTCOMES IF THOSE INSTRUMENTS ARE NOT APPROPRIATELY DESIGNED WITH THIS IN MIND. RISKS OF ANTIPLATELET THERAPY MAY BE HIGHER IN WOMEN DR. REYNOLDS MENTION TD THE ISSUE THERE WITH AGE AND WE KNOW THAT WOMEN HAVE MORE OF A BLEEDING PROBLEM. THAT'S BEEN DIFFICULT TO STUDY BECAUSE OF THE FEWER NUMBERS OF WOMEN IN THE CLINICAL TRIALS AND POOR SEX AND GENDER SPECIFIC REPORTING IN THE PAST. AND I FORGOT TO MENTION--LET ME JUST FINISH THIS IMPLICATION, SEX AND GENDER SPECIFIC REPORTING AND CLINICAL TRIALS ARE ESSENTIAL. I FORGOT TO MENTION IN MY INITIAL SLIDE THAT I'M NOT SHOWING YOU DATA ABOUT HOW OFTEN SEX SPECIFIC RESUMMITS ARE REPORTED BECAUSE THE PAPER CAME OUT A LONG TIME AGO BUT I WILL TELL YOU WHAT THE DATA ARE. WE LOOKED AT NIH PHASE THREE TRIALS PERFORMED OVER A 15 YEAR PERIOD, 28% HAD ANY SEX SPECIFIC RESULTS. 28% NIH PHASE THREE CLINICAL TRIALS. SO IN TERMS OF THE IMPLICATIONS OF SEX SPECIFIC RESPORTING, THERE'S MATERIAL THAT I WANT TO DRAW YOUR ATTENTION TO. WE SPONSORED WITH THE NATIONAL AKD--SALLY ME OF MEDICINE, THEN THE IOM, WITH THE SEX SPECIFIC REPORTING ON SCIENTIFIC RESEARCH. THE EUROPEAN ASSOCIATION OF SCIENCE EDITORS HAS COME OUT WITH SEX AND GENDER EQUITY AND RESEARCH GUIDELINES ISSUES THE GUIDELINES WHICH ARE DESIGNED FOR AUTHORS TO INFORM THEM AS TO HOW TO WRITE THEIR MANUSCRIPTS BUT ARE ALSO USEFUL FOR EDITORS WHO HAVE A KEY ROLE AS GATE KEEPERS IN IN SPACE AND THE JOURNAL STROKE HAS RECENTLY ADOPTED A REALLY CLEAR CHECK LIST THAT AUTHORS MUST COMPLETE REGARDING THE SEX OF SUBJECTS AND THE--THE SELECTION OF IF THEY'RE DOING A SINGLE SEX STUDY AND THEY ARE PUBLISHING THE CHECK LIST ON LINE ONLINE ACCOMPANYONYING THE PAPER WHICH IS A MUCH MORE AGGRESSIVE STEP AND WE APPLAUD THEM FOR TAKING THAT. IN DISEASEsS THAT EFFECT DEPRESSION THAT EFFECT ALMOST ANYONE AT ANY TIME OF LIFE, THERE'S THREE TIMES GREATER RISK OF DEPRESSION IN WOMEN THAN IN MEN YOU HAVE HEARD THAT STATISTIC BEFORE I'M SURE BUT WHEN INDIVIDUALS COME BACK TO LOOK AT TOOLS AND TRIEWMENTS THAT WERE USED TO ASCERTAIN THOSE WOMEN AND TO MAKE THE DIAGNOSIS OF DEPRESSION, THE PATTERNS OF DEPRESSION SEEN IN MEN WHICH WERE MORE RISK TAKING BEHAVIOR INCREASE SUBSTANCE ABUSE AND MORE ANGER AND OUTBREAKS WERE NOT THE PATTERN OF SYMPTOMS DETECTED BY THE INSTRUMENTS. SO WHEN THE INSTRUMENT WAS CHANGED SO THIS MORE MALE PATTERN WAS DETECTED THE PREVALENCE WAS EXACTLY THE SAME. SO WE HAVE TO LOOK AT HOW WE ARE DIAGNOSING OUR DECEASES, HOW WE'RE ASCERTAINING OUR SUBJECTS FOR OUR STUDIES AND LOOK AT THE VARIETY OF FACTORS IN IN CASE, BOTH SEX AND MALE AND FEMALE AND GENDER BEING A MAN OR WOMAN GENDER DIVERSE PERSON CONTRIUTE TO DEPRESSION. AS I MENTIONED THE SCREENING QUESTIONNAIRES AND THE INCLUSION/EXCLUSION CRITERIA, NEED NOT BE FORWARDED. WELL THIS IS WHAT THIS STUDY USED BUT SO I WILL USE THE SAME BECAUSE THIS IS THE RESULTS OF THE AND IF WE KEEP THAT APPROACH WE WILL NEVER TURN A CORNER AND WE ARE OFF-COURSE SO I CAN'T GIVE ANY TALKS ABOUT TALKING ABOUT THE NEW POLICY THAT ALL AWARE OF. THE NEW SEX IS A BIOLOGICAL VARIABLE, SABV POLICY THAT NIH EXPECTS THAT SEX ISsA I BIOLOGICAL VARIABLE WILL BE FACTORED INTO RESEARCH DESIGNS, ANALYSIS AND REPORTING IN VERTEBRATE ANIMAL INCLUDING HUMAN STUDIES. WE'RE TALKING ABOUT HUMAN STUDIES STUDY. WE ARE TALKING ABOUT THE ULTIMATE CLINICAL TRIALS AND THIS IS WHAT THIS SHOULD LOOK LIKE. WE ARE IN THE PHASE OF WHAT WE CALL SABV PHASE TWO WHERE WE'RE WORKING TO INTENTIONALLY INTEGRATE ACCOUNTING FOR SEX AS A BIOLOGICAL VARIABLE, DESIGN AND ANALYSIS REPORTING FROM THE PRECLINICAL SPACE WHERE YOUR INTENTION IS CLEARLY STATED THAT YOU ARE PREE CLINICAL, YOU ARE MODELING A HUMAN DISEASE, AND TRYING TO GO TO THE CLINIC TO ME THAT IS A HARD CHECK POINT THAT YOU'RE ACCOUNTING FOR SEX AS A BIOLOGICAL VARIABLE BEFORE YOU DO ANY FIRST IN HUMAN STUDIES. ALL THE WAY THROUGH TRANSLATION TO CLINICAL RESEARCH ALL THE WAY THROUGH ALL THE PHRASES OF CLINICAL TRIALS BACK THROUGH IMPLEMENTATION SCIENCE AND THEN, BEDSIDE TO BENCH WHEN WE INFORM OUR NEXT ROUND OF STUDIES. ALL OF THAT INFORMATION THEN CAN BE TRANSLATED THROUGH EDUCATION INTERPROFESSIONAL EDUCATION FOR OUR PHYSICIANS, OUR PHARMACISTS, OUR DENTISTS, EVERYONE NURSING, EVERYONE INVOLVED IN HEALTHCARE, IT SHOULD INFORM OUR POLICY IN ULTIMATELY OUR CARE. AND SO ORWH HAS DEVELOPED AN OUTREACH TOOL KIT I WANT TO REFER YOU TO. IT INCLUDES INFORMATION ON FEDERAL REGULATIONS, BEST PRACTICES AND CASE STUDIES ABOUT INCLUDING AND RETAINING WOMEN, AND YOU HEARD FROM THE DOCTOR PREVIOUSLY THAT YOU THOUGHT THAT OLDER WOMEN WILL NOT PARTICIPATE IN THIS STUDY, THAT WAS NOT THE CASE. IN FACT, ALSO, A GOOD PERCENTAGE OF THOSE PARTICIPANTS--EXCUSE ME PARTICIPANTS ARE MINORITY. SO I REFER YOU TO OUR WEBSITE FOR THAT INFORMATION AND HERE'S THE INFORMATION IF YOU WOULD LIKE TO TAKE A ELECTRIC AT OUR WEBSITE OR CONTACT US FOR MORE QUESTIONS. THANK YOU SO MUCH FOR YOUR ATTENTION. [ APPLAUSE ] MARIE DO WE HAVE TIME FOR ONE QUESTION? >> HI, JAMIE VICARY WITH THE MARCH OF DIMES. ONE OF THE ISSUES WE'VE BEEN CONCERNED ABOUT IS INCLUSION OF PREGNANT AND NURSING WOMEN IN CLINICAL RESEARCH AS A RESULT, THIS RARELY HAPPENS FOR A NUMBER OF REASONS AS WE CAN ALL IMAGINE. AS A RESULT WHY DON'T HAVE THAT--WE DON'T HAVE THAT DATA. DOCTORS DON'T KNOW IF A TREATMENT FOR SOMEONE WHO IS PREGNANT AND/OR BREAST FEEDING CAN TAKE THE MEDICATIONS THAT SHE NEEDS. I KNOW THAT--AS YOU KNOW THE TASK FORCE WAS INCLUDED IN THE CURES BILL, WE ARE VERY EXCITED ABOUT THAT. I WONDERED IF YOU COULD COMMENT ON THAT OR ANYTHING HOW THIS IDEA IS INCORPORATED INTO WHAT YOU ALL ARE DOING? >> SURE. THANK YOU FOR ASKING THAT, THAT IS AN ISSUE THAT NEED TREATMENT OF SUBSTANCE ABUSE BE ADDRESSED IN THE WORK GROUP AND I APPRECIATE YOU HIGHLIGHTING IT. IT REMAINS A PROBLEM AS YOU SAID. I'D LIKE TO QUOTED THIS PERSON, I CAN'T MPLE HER NAME NOW, SICK WOMEN GET PREGNANT AND PREGNANT WOMEN GET SICK AND AS YOU SAID DOCTORS HAVE VERY LITTLE INFORMATION TO MAKE ANYTHING CLOSE TO EVIDENCE-BASED DECISION TREATMENT IN MEDICINE. SO WE CLEARLY NEED TO DO BETTER WHAT ORWH HAS DONE ABOUT FIVE YEARS AGO, WE HAD A CONFERENCE ON ENROLLING PREGNANT WOMEN IN CLINICAL RESEARCH AND CALLED FOR THE CRETION OF A RESEARCH AGENDA,A ROUND THAT SPACE AND SO I'M REALLY PLEASED THAT THE TASK FORCE IS UNDERWAY AND I LOOK FORWARD TO WORKING WITH DR. BIANCI, AND OTHERS AROUND THOSE ISSUES BUT WE NEED TO HEAR FROM YOU IN TERMS OF REMENDATIONSATIONS AND IN TERMS OF IDEAS ABOUT THE SCIENTIFIC CONTEXT OF HOW TO APPROPRIATELY DO THAT IN YOUR OPINION. SO LOOKING FORWARD TO HEARING FROM THE WORKING GROUPS. >> JULIE FROM DARTMOUTH. AT THE OTHER END OF THE SPECTRUM, I'M WONDER WHAT IS KNOWN ABOUT NOT CLINICAL TRIAL ELIGIBILITY BUT CLINICAL INCLUSION FROM A VOLUME FOR WOMEN PARTICIPATING IN TRIALS AS A ROLE OF CAREGIVERS, AS PEDIATRICIAN AND INTERESTED IN ALZHEIMER'S DISEASE, YOU MIGHT SEE PEOPLE WHO ARE INTERESTED IN THE STUDY BUT DON'T HAVE THE WHERE WITH ALL TO DO IT. IS THERE ANYTHING IN YOUR LITERATURE OR YOUR EXPERIENCE WITH THAT? >> EXCELLENT QUESTION IN THE CARE LIMIT OF WOMEN AND LIKELIHOOD THEY COULD PARTICIPATE IN THE CLINICAL TRIAL. WE TYPICALLY HAVE LOOKED AT THE CHILDHOOD RESPONSIBILITIES OF THOSE WOMEN AND HAVE FOUND THAT INDEED CAN BE A BARRIER. I AM NOT AWARE OF LOOKING AT THE OTHER END OF THE SPECTRUM AND THAT'S A GREAT QUESTION AS WE START SEEING MORE AND MORE BABY BOOMERS IN THE SANDWICH GENERATION AND TAKING CARE OF BOTH CHILDREN AND ELDERLY RELATIVES AS WELL. BUT KEY POINT AND IT'S CERTAINLY ALIGNS WITH THE PREVIOUS PRESENTATION WHERE THERE ARE SPECIFIC THINGS THAT MIGHT NEED TO BE ADAPTED FOR THE DESIGN TO UNDERSTAND AND ACCOMMODATE THE NEEDS OF OLDER PEOPLE. >> YES, JAMES APPLEBY, EXCELLENT PRESENDATION, YOU MENTIONED IN YOUR PRESENTATION FROM NIH, AROUND SEX AND GENDER BEING VULNERABLE TO PROCESS, CAN YOU SAY TO WHAT LED THAT STATEMENT BEING MADE HOW DID IT ALL COME ABOUT? >> HOW THE QUESTION IS SEX AS A BIOLOGICAL VARIABLE POLICY AND I'LL JUST BRIEFLY MENTION BECAUSE I DON'T WANT TO TAKE UP MORE TIME AND WE HAVE ANOTHER SPEAKER WHO I WANT TO MAKE SURE WE GET TO THAT THERE WAS A PROCESS THAT INVOLVED REQUESTS FOR INFORMATION FROM THE SCIENTIFIC COMMUNITY AS WELL AS A TRANSNIH SEX AS A BIOLOGICAL VARIABLE WORKING GROUP AS WELL AS COLLABORATION WITH THE TRANSNIH WORKING GROUP ON ENHANCING REPRODUCIBILITY THROUGH RIGOR AND TRANSPARENCY OF WHICH THE SABV POLICY IS ONE COMPONENT. AND AS WELL AS A VARIETY OF OTHER CONSULTATIONS WITH THE COORDINATING COMMITTEE FOR RESEARCH ON WOMEN'S HEALTH AT NIH THAT'S MADE UP WITH CENTER AND INSTITUTE REPRESENTATIVES AND OUR ADVISORY COMMITTEE. SO, WITH THAT, I THINK I WILL CONCLUDE AND ASK DR. --THE NEXT DOCTOR TO COME UP AND JOIN US. [ APPLAUSE ] >> THANK AND YOU GOOD AFTERNOON. I'M GOING TO BE PRESENTING YOU TO ABOUT RACE, ETHNICITY AND SOCIAL ECONOMIC STATUS AND IT'S IMPORTANCE IN INCLOWGZ ACROSS THE LIFE SPAN. SO, LET ME SEE IF I CAN WORK THIS. SO WHICH ONE. >> YOU CAN USE THIS TO FORWARD. >> THAT'S WHAT I WANT, YES, THANK YOU. >> THESE ARE THE U.S. CENSUS OR OFFICE OF MANAGEMENT AND BUDGET CATEGORIES FOR RACE ETHNICITY JUST A REMINDER, THESE ARE THE NOMENCLATURE THAT WE USE, ASIAN WHICH IS PROBLEMATIC AND INCLUDES OVER 20 COUNTRIES NOTE THAT PACIFIC ISLANDERS ARE A SEPARATE RACE AND THEY ARE OFTEN LUMPED IN WITH ASIAN, THAT'S WRONG, AMERICAN INDIAN OR ALASKA NATIVE. NATIVE HAWAIIAN OR PACIFIC ISLANDERS THESE LAST TWO GROUPS ARE VERY SMALL AND LATINO OR HISPANIC WHICH IS AN ETHNIC GROUP. WHICH DOES INCLUDE MIDDLE EASTERN AND ARABS RIGHT NOW, ALTHOUGH THERE'S A ON POSAL IN 2020 TO CREATE A NEW ETHNIC CATEGORY. THESE ARE DATA EXTRACTED FROM A PRESENTATION THAT WE HEARD A COUPLE OF TIMES FROM MERIDETH O'CONNOR, WHO WAS IN CHARGE OF INCLUSION HERE IN THE OFFICE OF THE DIRECTOR AND THESE ARE DATA FROM 2010 AND 2014. IT WAS A CONTINUUM OVER FIVE YEARS ESSENTIALLY NO BIG CHANGE ACROSS THE PERIOD OF TIME. ALL MINORITIES INCLUDED IN ALL NIH CLINICAL RESEARCH IN THE U.S. ONLY, IT'S ABOUT 28, 26, APPROACHING 30% ONE YEAR. AND THEN BY RACE, CAN YOU SEE THAT FOR AFRICAN AMERICANS ABOUT 12%, FOR LATINOS FOR EXAMPLE, IT'S ABOUT EIGHT% LATINO POPULATIONS ABOUT 17%, ASIANS IS ABOUT FIVE OR 6 PERCENT AND THEN SO FORTH. THERE IS STILL A SIGNIFICANT NUMBER OF UNKNOWNS WHICH IS PROBLEMATIC. THAT IS ACTUALLY A DEFICIENCY THAT WE SHOULD BE ABLE TO ADDRESS BECAUSE THAT SHOULD'T BE EIGHT-13%, IT SHOULD BE WELL UNDER 5 PERCENT FOR FNIH FUNDED STUDIES--FOR NIH FUNDED STUDIES. AS FAR AS WHERE RACE MIGHT BE IMPORTANT I'LL JUST ILLUSTRATE A COUPLE OF POINTS. THIS IS DATA FOR INFANT MORTALITY AND ALL OF THE PROCESS AND INTERMEDIATE VARIABLES THAT LED TO THAT PREMATURE BIRTH, LOW BIRTH WEIGHT. COMPLICATIONS WOULD PARALLEL THIS, YOU CAN SEE FIRST OF ALL GOOD NEWS WE'VE MADE PROGRESS OVER THIS DECADE. FROM 2005 TO 2013. BUT THERE ARE MARKED DIFFERENCES BY RACE. AFRICAN AMERICAN CHILDREN HAVE A HIGHER RATE OF MORTALITY, SO DO AMERICAN INDIAN AMONG LATINOS DESPITE ADVERSE SOC SOCIOECONOMIC RATES AND AMONG PUERTO REEKA ANS YOU SEE THE HIGHEST RATE AND IGF 95 CANT IMPROVEMENT AND A RELEVANT POINT WHERE DIRECTING THIS AT THIS END BECOMES CRITICAL AND LOOK THING AT YOUR--AS FAR AS AX SESESMENT OF SOCIOECONOMIC STATUS IS CONCERNED THIS, IS SOMETHING WE DO VERY POORLY OF IN MOST OF OUR CLINICAL CARE AND IN I WOULD ARGUE IN CLINICAL RESEARCH. AS WELL. THE EASIEST METRIC TO COLLECT IS EDUCATION IT YEARS OF FORMAL EDCAUTION AND I WOULD STRONGLY--LOBBYING NIH TO MAKE THAT MORE OF A REQUIREMENT FOR PRINCIPLE INVESTIGATOR WHO IS DO HUMAN STUDIES TO COLLECT SOME METRIC OF SOCIOECONOMIC STATUS AND I THINK EDUCATION IS A SIMPLE ONE. YOU COULD ALSO JUST COLLECT THE ADDRESS AND GET THE ZIP CODE AND IMPUTE FROM THE CENSUS FROM A SECOND WAY OUT AS EASIER IN SOME CASES BUT MOST CLINICAL INVESTIGATORS DO COLLECT SOME METRIC OF SES AND YOU CAN SEE THE REST. INCOME IS PROBABLY THE MOST PROBLEMATIC PERHAPS THE MOST TELLING AND INDEED CONVINCING AS TO WHY THIS IS IMPORTANT THIS SIMPLE GRAPH WILL SHOW THAT IF YOU ARE UNDER THE POVERTY LINE FOR U.S. HOUSEHOLD INCOME, $25,000 A YEAR YOU ARE THREE TIMES MORE LIKE LE TO DIE THAN IF YOU ARE IN THE UPPER MIDDLE CLASS AND IF YOU ARE AT THE MEDIAN INCOME OF 50,000, YOU ARE TWICE AS LIKELY TO DIE THAN IF YOU ARE IN THE UPPER MIDDLE CLASS. SO THEREYA A POWERFUL CONSISTENT AND WELL KNOWN PREDICTER OF MORBIDITY AND MORTALITY, NOT ONLY ACROSS THE UNITED STATES AND ACROSS THE GLOBE BUT WE SHOULD BE LOOKING AT IT WHEN WE ARE LOOKING AT CLINICAL STUDIES AND CLINICAL DATA. WHERE THESE TWO INTERSECT, PERHAP THIS IS IS ANOTHER EXAMPLE OF NATIONAL DATA. COLORECTAL CANCER SCREENING CLEARLY A PROCESS WE'RE INTERESTED IN PREVENTING COLON CANCER, WE CAN SEE RATES VARY BY RACE, ETHNICITY WITH INSURANCE PLAYING A BIG ROLE WORLD WIDE WITH ASIAN, LATINOS AND ASIAN AND AMERICAN INDIANS ARE LESS LIKELY TO BE SCREENED. I WOULD NOTICE LITTLE GAPS BETWEEN THESE DATA IN CDC BUT YOU SEE A STRONG AND CONSISTENT GREET BASED ON EGZICATION USING LESS THAN HIGH SCHOOL GRADUATE, COLLEGE OR COLLEGE GRADUATE IN OBTAINING COLO RECTAL CANCER SCREENING. SO IMPORTANT NOT JUST IN DISEASE INSTANCE AND MORTALITY BUT IN OBTAINING SERVICES THAT MATTER. THERE ARE MANY OTHER SOCIAL DETERMINANTS. I WOULD NOT BE GIVING PROPER ATTENTION TO THIS TOPIC IF I DIDN'T MENTION THEM. SOME OF THEM ARE LISTED HERE. OF NOTE, FAMILY BACKGROUND OR HERITAGE IS IMPORTANT, IMMIGRANT STATUS, OBVIOUSLY, RELODGION, RESIDENTS IN RURAL AREAS IS INCREASINGLY RELEVANT AS WE'RE LOOKING AT CDCs REPORTING DATA ABOUT INCREASED MORTALITY IN THE MOST RURAL AREAS AND THE CHART THAT JANINE SHOWED IN THOSE AREAS SHOWED MANY OF THOSE COUNTYS WERE RURAL AND MOST OF THOSE ARE DRIVEN BY SOCIAL CLASS, SO POOR WOMEN WHO ARE HAVING INCREASED RATES OF MORTALITY. DISABILITY, SEXUAL ORIENTATION IS OTHER AREAS TO THINK ABOUT. SO WHY CONSIDER IN AN ENCLIEWGZ AND THE ACROSS THE LIFE SPAN IS RACE, ETHNIC CATEGORIES. THERE ARE SOME CONDITIONS THAT VARY BY RACE. SO AFRICAN AMERICAN GIRLS ARE KNOWN TO HAVE EARLIER ONSET OF PUBERTY, WHY THAT IS? A NUMBER OF SCIENTISTS ARE LOOKING AT THAT AND THERE'S A VARIETY OF HYPOTHESIS AND THERE'S A SITUATION WELL IS CONSISTENT. TYPE TWO DIABETES IN ADOLESCENCE WAS UNHEARD OF AS I STARTED MY TRAINING AS AN INTERNAL MEDICINE, AND NOW IT'S INCREASING COMMON AND NOW WE'RE SEEING INCREASE OF PHASE ONE DIABETES, AND CONFOUNDING RACE/ETHNICITY, WITH SES AND THOSE WITH SIGNIFICANT HEART FAILURE AS OPPOSE TO MUCH OLDER. OFTEN MINORITIES AND POOR PEOPLE ALREADY HAVE A DISEASE O THEY GET EXCLUDED FROM PREVENTION STUDIES OR ELIGIBILITY CRITERIA HAVE BEEN CREATED ON THE BASIS OF DATA FROM WHITES FOR EXAMPLE, THE RISK OF BREAST CANCER, THE GAIL MODEL WHICH WAS USED TO INCLUDE IN CLINICAL TRIAL WAS BASED BASIC LE ON WHITE WOMEN'S RISK. SUBSEQUENTLY HAS BEEN MODIFIED TO INCLUDE RISK IN OTHER RACE ETHNIC GROUPS THAT THE ORIGINAL TRIALS ARE BASED ON THAT AND THAT MAY INCLUDE PARTICIPATION AS WELL, WITH THE AGE RANGE AND I THINK THERE IS A CLEAR CONFOUNDER OF RACE ETHNICITY AND SOCIOECONOMIC STATUS AS TWO MAIN PILL OARARS OF SOCIAL DETERMINANTS, WITH DISEASE OFTEN BECAUSE OF LATE PRESENTATION, SOMETIMES DRIVEN BY ACCESS AND DRIVEN BY OTHER FACTORS. NOW, INCLUSION OF DIVERSE PARTICIPANTS AND BY THIS I MEAN THOSE OF RACE ETHNIC DIVERSITY, IS REALLY IMPORTANT AND THE HISTORICALLY HAVE BEEN UNDERREPRESENTED IN MEDICAL RESEARCH AND PROGRESS WHEN I FIRST SAW THOSE DATA THAT NIH FUNDED STUDIES WAS APPROACHING 30%. THOUGHT WELL, THAT'S MATT HOLT TOO BAD ALTHOUGH THESE DATAR NOT PERFECT. MINORITIES IN THE U.S. NOW MAKE UP ALMOST 40% OF THE POPULATION AND SOME PROJECTIONS OF DEMOGRAPHICS HAVE THE MINORITY, KNOWN MAJORITY POPULATION BY THE YEAR 2040. SOCIAL JUSTICE, COMMON SENSE, MANDATING INCLUSION BUT IT'S ALSO BETTER SCIENCE AND EVENTUALLY IF IT HELPS US ADDRESS HEALTH DISPARITIES IT MAKES PERFECT ECONOMIC SENSE BECAUSE HEALTH DISPARITIES ARE AN ECONOMIC BURDENOT UNITED STATES. --BURDEN ON THE UNITED STATES. THEY'VE BEEN INCLUDED ON TRIALS I THINK THIS HAS BEEN ALLUDED TO EARLIER, NOT EVERY STUDY NEEDS TO BE POWERED TO LOOK AT RACE ETHIC DIFFERENCES. THAT WOULD BE IMPOSSIBLE FOR INVESTIGATORS TO DO BUT SOMETIMES THE OBSERVATIONAL DATA SORT OF MANDATES THAT THIS BE DONE. YOU CAN'T DO A HYPER TENSION STUDY FOR EXAMPLE WITHOUT REALLY GIVING THOUGHT OF WHY AREN'T THERE A LOT OF AFRICAN AMERICANS IN THE STUDY BECAUSE OF THE DATA THAT WE KNOW. OR DIABETES AND HAVE LOTS OF MINORITIES. AND THERE ARE GOOD EXAMPLES OF GREAT STUDIES DONE IN THIS WHERE YOU WOULD THEN STRATIFY SAMPLING AND POWER TO BE ABLE TO TELL DIFFERECES BOTH BY RACE ETHNICITY AND IF NEED BY BE GENDER AND OTHER FACTORS. I THINK IN GENERAL PARTICIPANTS SHOULD BE REPRESENTATIVE OF THE POP IEWLINGSZ IN GENERAL, TO BE ABLE TO SEE WHETHER IS ANYTHING GOING ON, IF YOU DON'T INCLUDE PEOPLE, YOU WILL NEVER KNOW. AND FDA APPROVED SOMETHING LIKE 10 DRUGS IN 2015 FOR NOT UNCOMMON DISEASES, OF WHICH NONE OF THEM HAD MORE THAN 10% AFRICAN AMERICANS IN THE TRIALS THAT THEY REVIEWED. OF COURSE THESE ARE NOT PRENATIONAL LIBRARY OF MEDICINEINANT NIH TRIALS OR STREATSZ RUN TRIALS TO TO GIVE AN EXAMPLE OF WHAT WE'RE DOING AND THEN UNDERSTANDING THESE ISHT--IRPT--INTERACTIONS, IT'S IMPOSSIBLE TO TELL WHAT'S GOING ON IN THE ASPECTS OF DIFFERENT THERAPIES. I WILL JUST MENTION A FEW EXAMPLES OF WHY THIS IS IMPORTANT. FOR EXAMPLE, SERIES POINTS OHM COATINNINE WHICH IS USED TO IDENTIFY WHETHER SOMEONE'S A SMOKER. IT'S USED IN RESEARCH, NOT IN DRUG SCREENING NOT IN CLINICAL CARE. BUT IT'S BEEN WELL SHOWN THAT OPTIMAL CUT POINTS TO DEFINE SMOKING VARIES BY RACE ETHNICITY WITH WHITES, BLACKS AND MEXICAN-AMERICANS BEING DIFFERENT. THERE ARE DIFFERENTIAL CENTER FOR EXCELLENCE ON AGINGS OF SMOKING ON LUNG CANCER WITH AFRICAN AMERICANS HAVING THE HIGHEST BURDEN AND FOR THE SAME FOR ALDZ HYMER WHITES LATINOS HAD A 50% LOWER RELATIVE RISK OF LUNG CANCER FOR THE SAME AMOUNT OF CIGARETTE SMOKING. SO THERE IS A KNOWN CAR SIN CARCINOGEN BAD OUTCOME THAT WE HAVE UNEQUIV KALG DIAGNOSIS AND BY THE METHOD OF RACE WE SEE DIFFERENT CONSEQUENCES OF THAT. ALZHEIMER'S DISEASE, MORTALITY OR SURVIVAL IS DIFFERENT BY RACE AFTER DIAGNOSIS, EVEN THOUGH AFRICAN AMERICANS HAVE A HIGHER INCIDENCE OF ALZHEIMER'S IN THE BEST STUDIES, THE ACTUAL SURVERIFIAL AFTER DIAGNOSIS IS GREATER FOR AFRICAN AMERICANS THAN FOR WHITES AND LATINOS AS WELL. THERE'S A GENE THAT WAS AN ALLELE THAT WAS IDENTIFIED IN LATINO WOMEN OF AMERICAN INDIGENOUS BACKGROUND THAT PROTECTS FROM BREAST CANCER AND IT'S 15% PREVALENT IN THAT POPULATION. AGAIN, THAT DISCOVERY IS ONLY POSSIBLE IF YOU INCLUDE THESE DIVERSE SAMPLES AND DO STUDIES THAT ARE FOLK UTION OFFICE OF DIVERSITY THIS POPULATION. DIABETES RESULTS IN DIFFERENT RATES OF HEART ATTACKS AND END STAGE RENAL DISEASE BY RACE ETHNICITY SO GENERALLY MINORITIES HAVE LOWER RATES OF HEART ATTACKS COMPARED TO THEIR WHITE COUNTERPARTS WITH DIABETES IN A HEALTHCARE SYSTEM. BUT THEY ALL HAVE MUCH HIGHER RATES OFEND STAGE RENAL DISEASE OVER A 10 YEAR FOLLOW UP PERIOD AND IN THE STORY OF PLAF EXCITATORY AS I'LL MENTION IN A MINUTE, APOL ONE IS A RISK FOR KIDNEY FACTORS, IT'S PREDOMINANTLY FOUND IN POPULATION OF AFRICAN ANCESTRY. RESPONSE TO ALBEAUT ROL AS BY RACE ETHNICITY AND IN LATINO GROUP AND PUTER RIKE ANS DIFFER SLIGHTLY. THIS IS THE POLYMORPHISM IN THE ASIANS AND PACIFIC ISLANDER BACKGROUND. IT PREVENTINGS PLAVIX FROM BEING ACTIVATED FROM IT'S METABOLIZED FORM. THIS IS A COMMON ANTITHROMBOTTIC AGENT, ANTIPLATELET DRUG USED WITH CORONARY ARTERY DISEASE COMMONLY THAT IS LIKE A PLACEBO FOR PEOPLE WHO COME--HALF THE POPULATION WAS ASIAN AND OVER 60% OF THOSE WERE PACIFIC ISLANDERS. AND THIS IS NOT SOMETHING THAT WAS KNOWN BEFORE THE DRUG WAS MARKETED. SO IT'S POST MARKETING FINDINGS. SO AGAIN, THE CRITICAL ESSENCE OF INCLUDING INDIVIDUALS IN THESE SAMPLES. SO WE HAVE TO BE AT THE TABLE, WE HAVE TO--IT'S HARDER TO RECRUIT MINORITIES. IT ALMOST ALWAYS TAKES MORE RESOURCES, OR SOME DIFFERENT SETS OF SKILLS. THERE'S NO IMPERICAL GIED BOOK THAT SAYS HERE, YOU NEED TO GO DO, GO DO IT, THAT'S WHAT PEOPLE WANT BUT NOBODY'S BEEN ABLE TO GENERATE THAT. WE THINK THAT MORE TIME, MORE PERSONAL MESSAGE, YOU DON'T HAVE TO BE OF THE GROUP. IT DOES REALLY BENEFIT THE INVESTIGATORS TO ACTUALLY GO TO THE COMMUNITY, TALK TO LEADERS, AND DO PRESENTATIONS AND THE LEADER WILL BE YOUR ADHAVEICATES IN THE COMMUNITY IF YOU CAN CONVINCE THEM. WE FIND THAT MINORITY SCIENTISTS TEND TO BE MORE COMMITTED HAVE MORE PASSION AND BE MORE SUCCESSFUL AND I THINK NIH REALLY SHOULD BE I. ELEMENTING MORE ACCOUNTABILITY ON THIS TOPIC AND I USED UP THIS WORKSHOP TO MAKE THAT POINT SINCE WE SHOULD INCLUDE AGE AT BOTH ENDS OF THE SPECTRUM WE SHOULD ALSO REINTEGRATED INCLUDE RACE, ETHNICITY AND SOCIOECONOMIC STATUS WHICH WE DON'T COLLECT RIGHT NOW AND THE SAME DAT WAWE'RE PRESENTED EARLIER, I THINK DIANEA PRESENTED THE DATA ON HOW MUCH RECRUIT CHILDREN, REPORT OFFICE OF DIVERSITY IT, OR REPORTED DIFFERENTLY. YOU COULD DO THE SAME ON RACE-ETHNICITY AND WE COULD SEE THE SIMILAR RESULTS AND WE NEED TO END THE MYTHS THAT THESE THINGS ARE INSURMOUNTABLE SO THANK YOU. [ APPLAUSE ] QUESTIONS? >> OKAY, GREAT, THANKS. SO OUR FINAL SPEAKER BEFORE THE WORK GROUPS MEET IS DR. DR. CHRISTINE GRADE EXPE DEPARTMENT OF BIOETHICS AT THE CLINICAL CENTER AT NIH. . >> GUESS I RATE BECAUSE I GOT AN INTRODUCTION. SO IT'S RAN HONOR TO BE WITH YOU TODAY, I AM TALK ABOUT ETHICAL CONSIDERATIONS WHEN INCLUDING VULNERABLE POPULATIONS. SO UNLIKE THE PREVIOUS SPEAKERS I HAVE NO DATA. I DO HAVE SLIDES AND I WOULD LIKE TO TALK US THROUGH SOME CONCEPTS THAT I THINK--SOME OF WHICH WILL BE FAMILIAR WITH TO YOU AND SOME OF WHICH MAY NOT BE AS FAMILIAR. WHAT I HOPE TO DO IN THE FEW MINUTES THAT I HAVE IS TALK A LITTLE BIT ABOUT WHY VULNERABILITY MATTERS WHOSE VULNERABLE, HOW THEY'RE VULNERABLE AND HOW WE USE THAT INFORMATION TO DECIDE ABOUT INCLUSION VERSUS EXCLUSION AND THEN ADDITIONAL SAFE GUARDS. SO JUST AS A REMINDER, A LOT OF PEOPLE WHO HAVE SPOKEN ALREADY TODAY HAVE FOCUSED ON OUR ETHICAL RESPONSIBILITY, I PUT THE WORD ETHICAL IN THERE TO PROMOTE RESPONSIBLE AND USEFUL RESEARCH, TO FIND ANSWERS TO QUESTIONS THAT HELP PEOPLE AT EVERY STAGE OF LIFE IN EVERY CATEGORY OF THE POPULATION. SO WE BED THE ILLNESSES THEY HAVE AND DIAGNOSE AND PREVENT AND TREAT THEMENT AND THAT'S AN RESPONSIBILITY WE HAVE AS RESEARCHERS, IT IS HOWEVER, AS EVERYBODY IN THIS ROOM KNOWS CONSTRAINED BY THE FACT THAT WE ARE DOING RESEARCH ON PEOPLE. AND WE ARE DOING RESEARCH WHICH IS DIFFERENT THAN TAKING CARE OF PEOPLE AND THEREFORE THERE'S A RESPONSIBILITY OR A REQUIREMENT REALLY TO PROTECT THE RIGHTS AND WELFARE OF THOSE PROPII SYSTEMS PANT WHO IS MAY NOT BENEFIT FROM BEING PART OF THIS ENDEAVOR. WE ALSO KNOW WE HAVE A SORTED HISTORY OF USING WHAT PEOPLE CALL VULNERABLE POPULATIONS IN RESEARCH FROM PRISONERS TO ORPHANAGES TO INSTITUTIONALIZE MENTALLY ILL YOU MAY BE FAMILIAR WITH HENRY BEACHER'S FAMOUS 1966 ARTICLE OF 22 EXAMPLES ONE OF WHICH IS JEWISH CHRONIC DISEASE HOSPITALS WHICH WAS ELDERLY NURSING HOME RESIDENTS WHO WERE INJECTED WITH LIVE CANCER CELLS WITHOUT THEIR KNOWLEDGE. SO THIS IS A HISTORY WE HAVE AND A LOT OF THE WAY WE THINK ABOUT THE ETHICS OF RESEARCH IS BUILT ON THIS HISTORY. WE ALSO KNOW THAT THERE'S BEEN CHANGING VIEWS OVER THE LAST 20 YEARS OR SO, AND THAT PEOPLE ARE MORE STARTING WITH THE STEPS OF HIV ACTIVISM BUT NOT LIMITED TO THAT BUT CLAMORING FOR ACCESS TO TRIALS BUT NOT JUST TO DEVELOP EVIDENCE FOR GROUPS THAT ARE UNDERREPRESENTATIVE BUT TO ACTUALLY ALLOW ACCESS TO TRIALS FOR THE BENEFIT OF THEIR OWN BENEFIT, FOR THEIR OWN BENEFIT. SO WE HAVE THIS TWO FOLD EXISTENCE ABOUT RESEARCH. YOU KNOW WE THINK OF RESEARCH AS BURDENING PEOPLE AND PROPOSING RISKS TO PEOPLE FROM WHICH THEY NEED PROTECTION AND WE ALSO THINK OF RESEARCH AS BENEFITING PEOPLE TO WHICH THEY WANT AND NEED ACCESS AND THIS IS AT THE INDIVIDUAL LEVEL. SO THIS COMPLICATES THE ETHICS A LITTLE BIT, I WOULD SAY. ONE QUESTION I WOULD ASK IS HOW DOES VULNERABILITY FIT INTO THIS PICTURE. DOES VULNERABILITY TIP THE SCALES A LITTLE BIT IN A WAY THAT WE EMPHASIZE PROTECTION MORE THAN ACCESS, SO SHOULDN'T IT? DOES IT AND SHOULDN'T IT? AND THESE ARE QUESTIONS WE THEED TO ASK OURSELVES AND IT'S VERY RELEVANT TO THIS DISCUSSION. SO IN THAT LIGHT, I WANT TO ASK THE QUESTION WHAT IS VULNERABILITY. WHO IS VULNERABLE? YOU ALL KNOW THE FEDERAL REGULATIONS, AND FDA REGS WHO HAVE A COUPLE STATEMENTS ABOUT VULNERABILITY BUT DON'T DEFINE IT ANYWHERE BUT WHAT THEY DO IN THE REG SYSTEM TALK ABOUT GROUPS OF PEOPLE WHO ARE LOOKING FOR LISTS, ESPECIALLY WHAT WE'RE TALKING ABOUT, VULNERABLE POPULATIONS INCLUDING CHILDREN, PRISONERS PREGNANT WOMEN, MENTALLY DISSABLIED PERSONS OR ECONOMICALLY OR EDUCATIONALLY DISADVANTAGED PERSONS. THAT'S WHAT THE REG SAY. ANDLET FINAL RULE WHICH WAS PUBLISHED THIS LAST YEAR, PREGNANT WOMEN ARE NO LONGER ON THE VULNERABLE LIST ALTHOUGH WE HAVE REGULATIONS THAT ADD PROTECTIONS FOR PREGNANT WOMEN, MENTALLY DISABLED PERSONS WERE CROSS TD OUT BUT REPLACED WITH INDIVIDUALS WITH IMPAIRED DECISION MAKING CAPACITY. NOW THIS RULE HASN'T TAKEN EFFECT YET BUT IT LOOKS LIKE IT WOULD BY NEXT YEAR. SO WHO IS VULNERABLE. NOW THIS LIST IS INTENTIONALLY LONG. BUT NONE OF THESE DID I MAKE UP LET ME JUST TELL YOU. THEY CAME FROM REGULATIONS, GUIDELINES, LITERATURE AND IF YOU LOOK AT THE LIST, I WILL NOT READ IT BUT IF YOU LOOK AT TYOU MIGHT SAY, OH YEAH, I CAN SEE HOW THAT PERSON, THAT GROUP OF PERSONS MIGHT HAVE SOME VULNERABILITIES. THIS IS NOT AN EXHAUSTIVE LIST. THERE ARE OTHER GROUPS THAT YOU MIGHT THINK OF THAT SHOULD BE CONSIDERED SOMEWHAT VULNERABLE BUT ARE NOT. SO WHAT'S THE PROBLEM WITH A LIST LIKE THIS? THE PROBLEM IS IF ALL THESE PEOPLE ARE VULNERABLE, IF EVERYBODY'S VULNERABLE, VULNERABILITY LOSES ITS USEFULNESS. IF EVERYBODY'S VULNERABLE, NOBODY VULNERABLE SO THEREFORE WE HAVE TO THINK ABOUT WHAT VULNERABILITY MEANS IN THE CONTEXT OF RESEARCH AND HOW TO UNDERSTAND WHEN PEOPLE ARE VULNERABLE AND HOW TO ADDRESS VULNERABLE POPULATIONS AND THERE ARE EXTENSIONIVE LISTS LIKE THIS, AND WE KNOW THAT NOT ALL MEMBERS OF A GAY POPULATION ARE NECESSARILY OR SIMILARLY VULNERABLE. SO WE'VE TALKED ABOUT CHILDREN AND MANY PEOPLE HAVE REFERRED TO THE CHILDREN THAT YOU KNOW INFANTS ARE DIFFERENT THAN ADOLESCENTS BUT THEY'RE ALL CONSIDERED CHILDREN. THEY'RE NOT ALL SIMILARLY VULNERABLE AND SOME MIGHT ARGUE THAT AT ONE END OF THE SPECTRUM THEY'RE NOT THAT VULNERABLE AT ALL OR THEY'RE VULNERABLE TO DIFFERENT THINGS WANT IT'S ALSO TRUE THAT GROUPS OR INDIVIDUALS CAN BE POSSIBLY VULNERABLE. SO YOU MIGHT HAVE A CHILD WHO LET'S A AN ADOLESCENT WHO'S ALSO A WARD OF THE STATE OR SOMEBODY WHO HAS LESS CONTROL OVER HIS OR HER LIFE THAN ANOTHER ADOLESC EXPENT THAT PERSON IS VAL INNERRABLE FOR DIFFERENT REASONS AND THOSE ARE IMPORTANT TO THINK ABOUT MOVING AWAY FROM CATEGORYING WHOLE GROUPS OF PEOPLE AS VULNERABLE TO UNDERSTAND WHAT VULNERABILITY IS IN A MORE CONTEXTURAL WAY. I DON'T KNOW IF YOU'RE FAMILIAR WITH THIS DOCUMENT, THIS IS THE COUNSEL OF SCIENCES THAT HAS AN INTERNATIONAL GUIDELINE THAT WAS REVISED AND PUBLISHED AT THE END OF 2016. WHAT I LIKE ABOUT THEIR AND THEIR PREVIOUS VERSION AS WELL IS THAT THEY HAVE A DEFINITION OF VULNERABILITY. WHICH VERY FEW OTHER GUIDANCES HAVE AND THE DEFINITION IS, THAT PEOPLE ARE VULNERABLE IF THEY'RE RELATIVELY OR ABSOLUTELY INCAPABLE OF PROTECTING THEIR OWN INTERESTS. AND THAT'S AN INTERESTING THING TO THINK ABOUT. WHAT MAKES SOMEBODY INCAPABLE OF PROTECTING THEIR OWN INTERESTS IN THE CONTEXT OF RESEARCH. THEY GIVE EXAMPLES RELATIVE OR ABSOLUTE IMPAIRMENT IN DECISIONAL CAPACITY, EDUCATION, RESOURCES, STRENGTH, ET CETERA OR BEING IN A CIRCUMSTANCE IN WHICH OTHERS SORT OF NEGATE YOUR INTEREST AND THEREFORE IT'S HARD FOR YOU TO PROTECT YOUR OWN. I THINK THIS RESEARCH, WE DO THINK OF THIS SENSE OF VULNERABILITY AS THE MOST HELPFUL THAT INDIVIDUALS ARE VULNERABLE IF THEY HAVE A DIMINISHED ABILITY TO PROTECT THEIR OWN INTERESTS SINCE ONE OF THE WAYS THAT WE ALLOW PEOPLE OR REENCOURAGE OR REQUIRE PEOPLE TO PROTECT THEIR OWN INTERESTED AND RESEARCH IS BY GIVING INFORMED CONSENT, IT OFTEN COMES DOWN TO PEOPLE WHO CANNOT FOR SOME REASON OR HAVE DIMINISHED CAPACITY TO GIVE CONSENT AND THAT CAN COME IN LOTTINGS OF FLAVORS CAN YOU HAVE A DIMINISHED CAPACITY TO GIVE INFORMED CONSENT BECAUSE YOU DON'T HAVE THE CAPACITY TO RECEIVE INFORMATION OR UNDERSTAND INFORMATION OR PROCESS INFORMATION OR BECAUSE YOU DON'T HAVE THE CAPACITY TO DELIBERATE OR TO MAKE A DECISION OR BECAUSE YOU'RE IN A SITUATION WHERE YOU ARE NOT ALLOWED OR AUTHORIZED TO MAKE A DECISION. OR YOU ARE WORRIED ABOUT RETRIBUTION ABOUT A SPECIFIC DECISION SO THERE ARE LOTS OF REASONINGS THAT INABILITY TO MAKE INFORM CONSENT MAKE ITS HARD FOR PEOPLE TO PROTECT THEIR OWN INTERESTS AND THEREFORE THEY'RE VULNERABLE IN RESEARCH. SO, ONE MIGHT ASK WHAT DOES AGE HAVE TO DO WITH ANY OF THIS? AND I WOULD SAY SOMETHING THEY THINK MOST PEOPLE IN THIS ROOM ARE ALREADY AGREE WITH, AGE IS JUST A BLUNT STREEMENT TO TELL US ABOUT OTHER THINGS ESPECIALLY IN THE CONTEXT OF VULNERABILITY. SO, IT IS TRUE THAT PEOPLE AT DIFFERENT ENDS OF THE SPECTRUM MAY BUT NOT ALL DO, HAVE DECREASED CAPACITY TO UNDERSTAND INFORMATION OR TO MAKE DECISIONS. THEY MAY ALSO BE IN A POSITION OF DEPENDENCY AT ONE END OF AGE SPECTRUM OR THE OTHER. THEY MAY HAVE DIFFICULY SAYING NO IN CERTAIN CASES. THEY MAY HAVE NO LEGAL STANDING LIKE CHILDREN. OBVIOUSLY AGE ALONE, I THINK IS INSUFFICIENT TO SAY THAT SOMEBODY IS VULNERABLE. THERE ARE ELDERLY PEOPLE WHO ARE FRAIL AND HAVE DEMENTIA, THERE ARE OTHERS WHO ARE RUNNING FOR PRESIDENT OR RUNNING MARATHONS. THERE ARE CHILDREN WHO ARE TOTALLY DEPENDENT AND THEN, CHILDREN WHO HAVE DEVELOPED CAPACITIES TO UNDERSTAND, TO ENGAGE AND DECIDE. SO, AGE IS JUST A BLUNT INSTRUMENT AND IT'S NOT GOOD ENOUGH BY ITSELF TO SAY, A GROUP IS VULNERABLE AS ONE AGE OR ANOTHER. WE ALSO HAVE TO RECOGNIZE THAT PEOPLE ARE--PEOPLE ARE PEOPLE INCLUDING GROUPS AND INDIVIDUALS ARE VULNERABLE IN DIFFERENT REASONS OR DIFFERENT WAYS. SO EVEN IF THEY HAVE A COMPROMISED VAIBILITYD TO PROTECT THEIR OWN INTEREST THERE ARE WAY THIS IS WHICH THEY'RE MORE FINELY NUANCED, MAYBE VULNERABLE TO DECEPTION OR MISUNDERSTANDING OR NOT UNDERSTANDING AT ALL. THEY MAY BE VULNERABLE TO COERCION OR UNDUE INFLUENCE. THESE ARE IN THE REGULATIONS AND THEY REQUIRE UNPACKING BUT PEOPLE WHO ARE NOT ABLE TO MAKE DECISIONS FOR THEMSELVES BECAUSE THEY'RE INFLUENCED IN INAPPROPRIATE WAYS. VULNERABLE TO EXPLOITATION IN SITUATIONS WHERE THEY'RE TAKEN ADVANTAGE OF AND CAN'T PROTECT THEIR OWN INTERESTS IN THAT REGARD AND THEN VULNERABILITY IS OFTEN USED TO REFER TO RISK AS WELL, AND IT'S COME UP A FEW TIMES IN THE MORNING IN THE PRIOR SPEAKERS, IT'S A DIFFERENT KIND OF VULNERABILITY AND WE REALLY NEED TO BE ABLE TO SEPARATE WHEN IS A GROUP OR AN INDIVIDUAL GROUP VULNERABLE TO INCREASED RISK FOR WHEN THEY'RE VULNERABLE TO PROCESS INFORMATION AND THOSE ARE VERY DIFFERENT. SO, LET'S GO BACK TO THIS QUESTION, WHAT DO WE DO? WHAT DO WE DO ABOUT THIS DO WE PROTECT VULNERABLE GROUPS BY EXCLUDING THEM FROM RESEARCH OR DO WE ENABLE THEIR RESEARCH PARTICIPATION AND ALSO TRY TO RECOGNIZE THEIR PARTICULAR NEEDS IN THE CONTEXT OF RESEARCH? SO I--I WANT TO TURN TO, WHEN WE GO BACK TO THIS SLIDE THAT I SHOWED YOU EARLIER, YOU KNOW WE HAVE DUAL RESPONSIBILITIES IN THE CONTEXT OF RESEARCH ETHICALLY. ONE IS DOING RESPONSIBLE RESEARCH THAT GENERATED GET--IS NEW KNOWLEDGE THAT HELPS US TREAT PEOPLE IN THE CLINIC AND THE OTHER AND IN THE COMMUNITY AND OTHER PLACES. AND THE OTHER IS TO MAKE SURE WE PROTECT THE RIGHTS AND WELFARE OF PEOPLE WHO HELP US GET THERE. SO ONE THING WE TALK ABOUT, IN RESEARCH ETHICS A LOT IS THE NOTION OF FAIR SUBJECT SELECTION AND I THINK IT'S INTERESTING TO THINK ABOUT IT FOR ONE MINUTE. WHAT DOES THAT MEAN? IT MEANS IN MOST CASES THAT WE SELECT PEOPLE FOR PARTICIPATION AND RESEARCH BASED ON WHETHER THEY'RE SCIENTIFICALLY APPROPRIATE FOR INCLUSION IN A STUDY BUT IT DOESN'T END THERE, WE ALSO TAKE INTO ACCOUNT IF THEY'RE AT PARTICULAR RISK, OR IF THEY'RE MORE LIKELY TO BENEFIT THAN ANOTHER GROUP OR ANOTHER SET OF INDIVIDUALS AND ALMOST EVERYBODY SAYS AND THE OTHER THING WE TAKE INTO ACCOUNT IS VULNERABILITY. SO IF YOU FLIP THIS AROUND AND A LOT OF PEOPLE HAVE DONE THIS IN THE THINKING OF FAIR SUBJECT SELECTION, ONE MIGHT SAY THAT THE FAIREST WAY TO SELECT SUBJECTS OR PARTICIPANTS FOR A STUDY IS TO SAY EVERYBODY IS ELIGIBLE UNLESS THERE'S A GOOD REASON TO EXCLUDE THEM AND SO WHAT ARE THE GOOD REASONS TO EXCLUDE THEM? THEY ARE REALLY THE INVERSE OF THIS IN MY VIEW, THE INVERSE. IF SOMEBODY IS INAPPROPRIATE SCIENTIFICALLY, OBVIOUSLY YOU WOULD BE MORE--WELL ADVISED TO EXCLUDE THEM. IF THEY HAVE OR ARE SUSCEPTIBLE TO A RISK OR ARE BURDENED IN A WAY THAT CANNOT BE MITIGATED OR JUST AS THEY MAY BE JUST FIELD FUNCTIONSABLY EXCLUDED. AND THEY'RE VULNER ANNUAL IN WAYS WE CANNOT ADEQUATELY ADDRESS IN THE CONTEXT OF RESEARCH, THEN THEY MAY BE JUSTIFIABLILY EXCLUDED. SO WHAT ABOUT THIS EXCLUSION, INCLUSION CHOICE. IT'S REALLY--A REALLY IMPORTANT ONE TO THINK ABOUT CAREFULLY, AND IT'S ALSO ONE THAT HAS CHANGED HISTORICALLY. SO AS YOU KNOW, THERE ARE EXTRA PROTECTIONS IN THE REGULATIONS FOR EXAMPLE FOR CERTAIN GROUPS THAT PRIORITIZE PROTECTION AND ACTUALLY SAY EXCLUSION IS--AT LEAST REFERENCE IN SELECTION IS THE WAY WE SHOULD THINK ABOUT HOW WE INCLUDE PEOPLE IN RESEARCH. SO WE SHOULD EITHER EXCLUDE VULNERABLE GROUPS OR CERTAIN GROUPS OR FOLLOW IN ORDER OF PREFERENCE THAT FOR EXAMPLE, ADULTS BEFORE CHILDREN THAT PROTECTS THE BURDEN. THIS IS FROM THE BELMONT REPORT, THIS IS THE WAY REGULATIONS READ, ET CETERA. SOME OF THE COMMON--THE CURRENT DAY GUIDANCE HAS A SIMILAR KIND OF RESTRICTION AND THAT SAYS THAT PEOPLE WHO ARE VULNERABLE SHOULD ONLY BE INCLUDED, EXCUSE& ME IF THEY HAVE--IF THEY ARE--IF THE STUDY IS ABOUT A CONDITION THAT THEY HAVE. SO IN OTHER WORDS, IT'S WHAT SOME PEOPLE CALL SUBJECT CONDITION REQUIREMENT OR NECESSITY. IN LITTLER WORDS YOU NEED TO HAVE PEOPLE WITH A CERTAIN DISEASE. YOU CAN ONLY STUDY PEOPLE WITH THAT DISEASE, YOU 92 ED TO INCLUDE THEM, AND--YOU NEED TO INCLUDE THEM AND THE ONLY JUST ISKEDZ FOR PEOPLE WHO ARE VULNERABLE IS IF THAT'S THE CASE. HOWEVER, THE DEFAULT HAS BEEN SHIFTING AND WE KNOW THAT THE DEFAULT SHIFTED BECAUSE FOR EXAMPLE, IN CHILDREN, WE ARE OFTEN ASKED EVEN THOUGH THERE ARE PROTECTIONS THAT MAKE IT HARD TO INCLUDE CHILDREN IN SOME CASES THERE IS A REQUIREMENT TO JUSTIFY EXCLUDE CHILDREN AND NOT INCLUDE CHILDREN SO THE DEFAULT SHIFTED. SO THE GUIDELINES I REFERRED TO EARLIER TALKS ABOUT ALSO ADULTS WHO ARE NOT CAPABLE OF GIVING INFORMED CONSENT THAT THE DEFAULT SHOULD SHIFT THAT THEY SHOULD BE INCLUDED UNLESS THERE IS A SUFFICIENT SCIENTIFIC REASON TO JUSTIFY THEIR EXCLUSION. IT'S A CONVERSATION WE'VE HAD REPEATEDLY ABOUT PREGNANT WOMEN. WOMEN SHOULD BE INCLUDED AND UNLESS THERE'S A REASON NOT TO INCLUDE THEM PREGNANT WOMEN IN MY VIEW SHOULD ALSO, HOWEVER, THAT'S NOT THE DEFAULT, DEFAULT IS TO EXCLUDE THEM CURRENT LOAMACYY A REASON TO ENCLUED THEM. SO ANOTHER IMPORTANT CONSIDERATION HERE IS THE RISK AND BENEFIT DISCUSSION. NOW I KNOW THAT MOST OF THE FOCUS TODAY HAS BEEN ON CLINICAL TRIALS AND SOME PEOPLE WOULD ARGUE THAT CLINICAL TRIALS FALL MOSTLY ITO THE CATEGORY OF STUDIES THAT OFFER THE PROSPECT OF CLINICAL BENEFIT. AND SO YOU MIGHT THINK THAT EACH IF SOMEBODY IS VULNERABLE IN A CERTAIN WAY, EXCLUDE THEM FROM SOMETHING THAT OFFERS THEM THE POTENTIAL FOR CLINICAL BENEFIT, SPECIALLY IF IT'S THE CLIN KALE BENEFIT THEY CAN'T GET ELSEWHERE OR IT'S JUST AS MUCH BENEFIT AS THEY MIGHT GET OUTSIDE OF THE TRIAL IS NOT--YOU CAN'T JUSTIFY EXCLUDING THEM. SO THAT'S AN IMPORTANT THING, BUT NOT ALL TRIALS ARE PROSPECTIVE CLINICAL BENEFIT, RIGHT? SO MOST PEOPLE FEEL THERE'S SOME ARGUMENT, NOT EVERYBODY, BUT MOST PEOPLE FEEL THERE'S SOME ARGUMENT FOR INCLUDING VULNERABLE PEOPLE IN--SORRY, PROSSPECTIVE BENEFIT. MANY PEOPLE FIND IT PERFECTLY OKAY TO INCLUDE PEOPLE WHO ARE OTHERWISE UNABLE TO PROTECT THEIR OWN INTERESTS IN MINIMAL RISK STUDIES BECAUSE WE'RE NOT EXPOSING THEM TO MUCH RISK AND IT'S OKAY IF WE PUT OTHER SAFE GUARDS INTO PLACE. THE TRICKIEST CATEGORY IS THE THIRD ONE. STUDIES THAT POSE GREATER THAN MINIMAL RISK BUT DON'T OFFER THE PROSPECT OF BENEFIT. I WOULD SAY A VERY LARGE PERCENTAGE OF PEOPLE WHO THINK ABOUT THIS SAY WE SHOULD EXCLUDE THOSE WHO ARE VULNERABLE. THOSE WHO CAN'T--PROTECT THEIR OWN INTERESTS. AND SO, AND YOU WILL SEE DIFFERENCES. I MEAN I THINK ADULT WHO IS DON'T HAVE THE CAPACITY TO CONSENT, A LOT OF PEOPLE WOULD SAY THIS IS THE CASE. CHILDREN, A LOT OF PEOPLE AND THE REGULATIONS REQUIRE SPECIAL STEPS IF YOU ARE GOING TO DO THE LATTER. SO I WANT TO SWITCH NOW TO END WITH SAFE GUARDS. SO THERE'S--LET'S SAY THERE ARE NO GOOD JUSTIFICATIONS FOR EXCLUDING GROUPS OF PEOPLE WHO ARE HAVE DIMINISHED CAPACITY TO PROTECT THEIR OWN INTERESTS. WE WANT TO INCLUDE THEM BUT WE SHOULD ALSO THINK ABOUT THIS NEED TO PROTECT THEM, TO PROTECT THEIR RIGHTS AND WELFARE AND SO THE REGULATORY GUIDANCE THAT EXISTS SAYS WE SHOULD ADD SPECIAL PROTECTIONS OR ADDITIONAL SAFE GUARDS OR I MEAN YOU COULD SEE THE DIFFERENT WORDING, IT'S BASICALLY THE SAME THING. THAT IF PERSONS OF THIS--IN THESE CATEGORIES WILL BE INCLUDED THERE WILL NEED TO BE ADDITIONAL SAFE GUARDS. SO IT'S AN IMPORTANT CONVERSATION TO HAVE, WHAT ARE ADDITIONAL SAFE GUARDS AND HOW DO THEY PROVIDE PROTECTION AND ADDITIONAL PROTECTION FOR PEOPLE IF WE ARE GOING TO INCLUDE THEM IN STUDIES. AND I HAVE JUST A--NOT RANDOM LIST BUT PROBABLY NOT EXHAUSTIVE LIST OF SOME OF THE ADDITIONAL SAFE GUARDS THAT ARE USED AND SOME GUIDANCE THAT DOES RECOMMEND THEIR USE. SO LIMITS ON RISK IS ONE. SO YOU ALL--MAYBE MANY OF YOU KNOW THE REGULATIONS ON INCLUDING CHILDREN IN RESEARCH ACTUALLY DO MAKE DISTINCTIONS BASED ON THE AMOUNT OF RISK AND BENEFIT, AND SO, ONE WAY TO PROTECT CHILDREN IN THE CONTEXT OF RESEARCH IS LIMITING THE AMOUNT OF RISK THAT THEY'RE ALLOWED TO BE EXPOSED TO. THIS IS ALSO TRUE FOR PREGNANT WOMEN. REPRESENTATION ON IRBs, THIS IS NOT IN THE REGULATORY LANGUAGE, BUT IT'S SOMETHING THAT A LOT OF PLACES DO, EXCEPT PRR PRISONERS, IT IS, A LOT OF PEOPLE THINK IT'S VERY IMPORTANT TO INCLUDE A PERSON WHO CAN REPRESENT THE INTERESTS OF THE VULNERABLE GROUP ON THE IRB THAT'S REVIEWING STUDIES THAT INCLUDE THOSE VULNERABLE GROUPS. WE BASICALLY ADOPT THE IDEA THAT IF SOMEBODY IS NOT ABLE TO CONSENT FOR THEMSELVES, WE GET PERMISSION FOR THEIR ENROLLMENT FROM A LEGALLY AUTHORIZED REPRESENTATIVE, USUALLY FOR KIDS IT'S PARENTS OR LEGAL GUARDIANS. FOR ELDERLY ADULTS IT'S MORE COMPLICATE INDEED TERMS OF REGULATORY ALLOWANCES BUT STILL, THERE CAN BE PEOPLE WHO HAVE THE LEGALLY AUTHAUTHORIZED AUTHORITY TO GIVE PERMISSION FOR SOMEBODY WHO CAN'T CONSENT FOR THEMSELVES AND AN ADULT. WE ALSO THINK A PARTICIPANT TO THE EXTEND THAT THE PARTICIPANT IS CAPABLE EVEN IF IT'S IMPORTANT AND IF SOMEBODY ELSE IS GIVING THEIR PERMISSION FOR THEM. THESE ARE OTHER THINGS THAT ARE PROBABLY LESS--LESS YOUTHFULLY ADOPTED BUT I THINK ITADS PROTECTIONS IN CERTAIN CASES. INDEPENDENT CONSENT MONITORS FOR PEOPLE WHO MIELT BE VULNERABLE IN THE WAY THEY MAY FEEL UNABLE TO OR SAY NO. AND YOU GET AN INDEPENDENT CONSENT MONITOR IN THE PROCESS THAT CAN TALK TO THE PERSON BOTH, WITNESS THE CONSENT PROCESS ITSELF BUT TALK TO THEM AFTERWARDS ABOUT WHAT THEY REALLY WANT TO DO THAT'S SOMETHING THAT PROVIDES ADDITIONAL SAFE GUARDS FOR VULNERABLE POPULATIONS. MECHANISMS TO ALLOW REFUSAL WITHOUT PRESSURE OR RETROBUTION. NOW WE KNOW THAT THE REGULATIONS REQUIRE THAT RIGHT? BUT THE REALITY IS IN CERTAIN CIRCUMSTANCES PEOPLE FEEL WORRIED ABOUT THAT. YOU KNOW I CAN'T SAY NO, MY PARENTS WILL KILL ME. I'VE HAD ADOLESCENTS SAY THAT TO ME FOR EXAMPLE. A MEDICAL MONITOR TO MONITOR FOR RISK. ADVOCATES TO HELP INDIVIDUALS WITH THEIR INTERESTS, PROTECT THEIR OWN INTERESTS TO GIVE THEM VOICE AND WAYS THAT GIVES THEM POWER THAT THEY MAY NOT OTHERWISE HAVE. AND THESE ARE JUST SOME EXAMPLES. I'M HOPING THAT THE GROUP, THE WORKSHOP GROUP WILL COME UP WITH OTHERS. SO TO CONCLUDE I JUST WANT TO SAY WHEN WE'RE PROMOTING RESEARCH TO ADDRESS THE HEALTH NEEDS OF VULNERABLE GROUPS AND TO INSURE TAKEN--THEY WE HAVE REPRESENTATIVE GROUPS SO WE CAN ANSWER QUESTIONS THAT NEED TO BE ANSWERED IN THE CLINIC IN WHAT WORKS IN SOMEBODY WHO'S 75 OR 90 OR WHAT WORKS IN A PERSON WHO'S PREGNANT? WE NEED TO ALSO CONSIDER SOMETIMES OF VULNERABILITY AND THE APPROPRIATE ADDITIONAL PROTECTIONS FOR THOSE WHO ARE VULNERABLE. AND I THINK DR. BIANCI, SAID SOMETHING I WANT TO REITERATE AND MY VIEW IS THAT THIS HAS TO BE A CASE BI CASE DETERMINATION, THAT VULNERABILITY ALTHOUGH IT COMES UNDER THIS CATEGORY IN MOST CASES OF REDUCED CAPACITY PROTECT ONE'S OWN INTEREST, THAT LOOKS DIFFERENT IN DIFFERENT GROUPS AND IN DIFFERENT INDIVIDUALS AND SO, IN DIFFERENT--IN PROTOCOL BY PROTOCOL WE SHOULD ADDRESS WHO ARE THE PEOPLE THAT WE WANT TO INCLUDE. WE SHOULD IDENTIFY HOW THEY MIGHT BE VULNERABLE AND WHETHER THEY'RE VULNERABILITY CAN BE ADEQUATELY ADDRESSED IN THE CONTEXT OF THE STUDY AND IF NOT, MAYBE EXCLUSION IN SOME CASES IS APPROPRIATE. THAT'S IT. [ APPLAUSE ] DO I HAVE TIME FOR QUESTIONS? OR CHALLENGES? >> HI, THERE, SO I'M FROM THE UNIVERSITY OF WISCONSIN. SO ONE THING THAT STRIKES ME IN WHAT YOU PRESENTED IS THAT YOU USE THE WORD VULNERABLE STARTS OFF AT A PLACE OF NO, RATHER THAN YES, AND I THINK THAT'S BEEN A CHALLENGE ESPECIALLY FOR PEDIATRIC RESEARCH IS THAT WHEN YOU CHARACTERIZE SOMEBODY AS VULNERABLE, YOU PLACE THEM AS A DISADVANTAGED POSITION, AND WE ETHICALLY WANT TO PROTECT THEM BUT IN DOING SO IN THAT PROTECTION, WE END UP EXCLUDING THEM AND WE END UP PUSHING POETIC POETIC POTENTIAL DISEASES OR PROBLEMS OR ISSUES OUT OF THE POSSIBILITY. IS THERE A WAY TO CHANGE HOW ETHICISTS USE THAT WORD OR THINK ABOUT CHILDREN OR THE AGED AND USE A LESS--ANOTHER TERM THAT DOESN'T PLACE US IN A DEFENSIVE POSTURE IF TERMS IN YOU SIT ON AN IRB OR ANYTHING ELSE? >> DO YOU HAVE A SUGGESTION FOR A WORD? >> I DO NOT BUT I SEE IT AS A PROBLEM BECAUSE IMMEDIATELY WHEN YOU PUT CHILDREN IN, THE PEOPLE IN THE IRB SAY NO BEFORE LOOKING AT THE STUDY AND ADDRESSING WHETHER IT SHOULD BE YES BECAUSE WE NEED TO DO THIS FOR THE CHILDREN. SO THEY'RE STARTING OFF BY SAYING IT'S CHILDREN, CHILDREN ARE VULNERABLE, THEREFORE WE HAVE TO DO EXTRA ANALYSIS OF THIS WHICH PLACES EVERYBODY IN LOOKING FOR A PROBLEM RATHER THANOT OTHER WAY OF SAYING THAT IT'S A NEED SO WE HAVE TO LOOK FOR SOLUTION AND SO WE--I'M JUST WONDERING, IS THERE ANYTHING IN THE-- >> I THINK YOU RAISE A VERY IMPORTANT POINT AND THAT IS THAT LANGUAGE MATTERS. IT ALSO MATTERS THAT WE DON'T MAKE CATEGORICAL DECISIONS ABOUT THINGS LIKE CHILDREN ARE VULNERABLE AND THEREFORE WE EXCLUDE THEM, THAT'S--THAT'S NOT WHAT WE SHOULD BE DOING AND I HOPE I--SORT OF MADE NODS AS TO WHERE WE SHOULDN'T BE DOING THAT. I DON'T KNOW THAT JUST CHANGING THE WORTD WILL FIX THE PROBLEM, IT MIGHT. I DO THINK THAT THEY'RE--DEPENDING ON HOW YOU UNDERSTAND THE WORD VULNERABLE, THERE ARE WAYS IN FACT THAT CHILDREN ARE VULNERABLE AND SO, INCLUDING THEM IN RESEARCH IS VERY IMPORTANT BUT PROTECTING THEM IS ALSO VERY IMPORTANT I GUESS IS THE WAY WE WOULD SAY IT SO RESPONSIBLE INCLUSION IS A WAY THAT I LIKE TO THINK ABOUT INCLUSION. THE CONVERSATIONS AT THE IRB LEVEL, IT'S NOT JUST IRBs AND ETHICISTS BUT YOU KNOW THE WORLD TALKS ABOUT VULNERABILITY IN A WAY THAT IS NOT PREICIZE AND SO PRECISION ABOUT WHAT WE MEAN, HOW IS THIS PERSON OR THIS GROUP VULNERABLE IN THIS CONTEXT IS GOING TO BE PROBABLY THE BEST WAY TO GET TO YES AS YOU VIEW IT ANYWAY. >> THIS IS FASCINATING TALK AND SO, GETTING BACK TO--YOU TALKED ABOUT WHEN MIGHT EXCLUSIONS BE JUSTIFIABLE AND I'M CURIOUS AND WOULD LOVE TO HEAR YOUR THOUGHTS ABOUT OLDER ADULTS THAT HAVE IN ADDITION TO THE CONDITION OF INTEREST HAVE OTHER CONDITIONS, THESE ARE PRETTY TYPICAL EXCLUSIONS WE SEE IN TRIALS. THE EXAMPLE OF EGFR BEING ONE OF THEM THAT THE PERSON IS AT POTENTIALLY A HIGHER RISK OF THE SIDE EFFECT BUT YET THE POPULATION WITH THAT CONDITION, YOU KNOW SOMETIMES 40% OF THEM WILL HAVE AN IMPAIRED GFR. SO, HOW DO WE THINK ABOUT POTENTIALLY MITIGATING--SO YOU TALKED ABOUT WHEN RISKS OR BURDENS CAN BE MITIGATED OR JUSTIFIED SO THIS PERSON MAY NOT MEET THE TYPICAL DEFINITION OF VULNERABLE YET THEY'RE OFTEN EXCLUDED AND I WOULD BE INTERESTED IN HEARING YOUR THOUGHTS ABOUT IT. >> SO IT'S A GREAT QUESTION AND I WOULD LOVE TO HEAR OTHER'S VIEWS ON THIS AS WELL BUT MY PERSPECTIVE IS THE FOLLOWING: THAT'S WHY IT'S SO IMPORTANT TO BE CONTEXTURAL. IN OTHER WORDS TO DO IT ON A CASE BY CASE BASIS. IF THE STUDY THAT YOU'RE TALKING ABOUT WANTS TO ENROLL ELDERLY PEOPLE TO USE A DRUG THAT HAS--YOU KNOW KIDNEY TOXICITY, AND IT'S AN EFFICACY TRIAL, SOMEBODY MADE A GOOD POINT EARLIER ABOUT, YOU KNOW WHERE WE ARE AT THE STAGE OF DETERMINING WHETHER THIS THING WORKS, IT MAY MAKE SENSE AT THE FRONT END TO LIMIT THE PEOPLE THAT HAVE THE WORST KIDNEY FUNCTION. BUT IF THOSE ARE THE PEOPLE WHO ARE GOING TO--IF ONLY THOSE OR THOSE PEOPLE WILL BE THE PEOPLE USING THE DRUG THEN WE HAVE TO HAVE ANOTHER STUDY THAT INCLUDES THEM. SO THE QUESTION IS AT WHAT POINT DO YOU ENCLUED THE PEOPLE WHO ARE AT THE HIGHEST RISK AND I REALLY THINK IT DEPENDS ON THE CONTEXT. YOU KNOW IF YOU ARE GOING--PART OF THE PROBLEM, IT GETS BACK TO THE PREVIOUS QUESTION AS WELL IS TO NOT SAY, ALL OLD PEOPLE--I WOULD NEVER SAY THAT SINCE I'M ONE OF THEM, ALL OLD PEOPLE HAVE REDUCED KIDNEY FUNCTION THEREFORE WE EXCLUDE PEOPLE OVER A CERTAIN AGE. YOU KNOW? UNJUSTIFIED CHOICE OF AGE 65 IS SOMETHING THAT WE SHOULD GET AWAY FROM. BUT, IN THE CONTEXT OF A PARTICULAR TRIAL, IF THERE'S SOMETHING THAT WE'RE TESTING THAT HAS A HIGH RISK OF WHATEVER IT IS THAT PEOPLE IN THIS CATEGORY MIGHT HAVE, I THINK THAT'S AN IMPORTANT CONSIDERATION AND SOMETIMES IT NEEDS TO BE AN EXCLUSION. >> DONNA STEINER FTD OFFICE OF THERAPEUTIC. ONE POINT WE WANT TO MAKE IS THAT WE ARE TAKING THE OPROACH THAT WE WANT TO PROTECT CHILDREN FROM RESEARCH AND THROUGH RESEARCH. SO SO WHEN A DRUG BECOMES APPROVED AND THEY'RE TAKING THE DRUG OFF-LABEL SO WE LIKE TO BE ABLE TO COLLECT THAT INFORMATION IN A CLINICAL TRIAL SO WE CAN BE SURE WHAT THE DOSE IS AND THE SAFETY RISK IT IS ARE BEFORE EXPOSING THAT CHILD TO THE PRODUCT ONCE IT'S OUT ON THE MARKET 6789. >> YEAH, IT'S A VERY--IT'S A CATCHY PHRASE AND PEOPLE ARE USING IT FOR ALL KINDS OF DIFFERENT GROUPS INCLUDING CHILDREN, INCLUDING PREGNANT WOMEN, I THINK--AND I'VE USED IT MANY TIMES MYSELF, I THINK THE ONLY WAY WE LEARN HOW TO TREAT PEOPLE WHO ARE CHILDREN OR PREGNANT WOMEN OR FRAIL ELDERL IS BY INCLUDING THEM IN RESEARCH. THAT DOESN'T MEAN THAT WE INCLUDE THEM IN EVERY STUDY. AND MY POINT IS YOU KNOW THOUGHTFULNESS ABOUT HOW WE INCLUDE THEM AND WHY WE INCLUDE THEM OR WHY WE EXCLUDE THEM IS WHAT WE SHOULD BE DOING. I MEAN I THINK INCLUSION FOR INCLUSION'S SAKE IS NOT NECESSARILY A GOOD THING. IT COULD BE, IF YOU CAN'T GET ANY SCIENTIFIC VALUE FROM INCLUDING PEOPLE, IF YOU ARE EXPOSING THEM TO RISK WITHOUT ANY BENEFIT, THEN THE QUESTION IS, WHY INCLUDE THEM? WHERE'S THE FAIRNESS THERE? >> HI, WILLIAM FROM THE CITY OF HOPE CANCER CENTER. FASCINATING TALK, I REALLY APPRECIATED THIS CHALLENGE WE HAVE, MY QUESTION IS ABOUT INCENTIVES A LITTLE BIT--AND THE RIGHT RULES ENROLLMENT OF OLDER ADULTS, WON'T HAPPEN IF THE REQUIREMENTS FOR DRUG APPROVALS DON'T HAVE ANY TEETH TO THEM, TO SAY, YOU HAVE TO INCLUDE THESE PEOPLE BEFORE THEY GO ON THE MARKET. SO WITHOUT THAT, STICK IT WON'T MATTER HOW MUCH WE WORK TO INTELLECTUALLY GET IT RIGHT. AND SOMETIMES THE IRBs WITHIN OUR OWN INSTITUTIONS THERE'S AT LEAST THE CONSIDERATION THAT THEY'RE MORE CONCERNED ABOUT PROTECTIONS FOR INSTITUTION RATHER THAN FOR THE PEOPLE. SO THOUGHTS ON HOW TO CHANGE THAT? IT'S BEEN A--DIFFICULT TO INCENTIVIZE PEOPLE AND THAT'S OUTSIDE THE DISCUSSION A LITTLE BIT. >> YEAH, I WISH I HAD AN ANSWER AND HOW TO CHANGE THE INCENTIVE STRUCTURES, I THINK IN PEDIATRICS IT'S HAPPENED A LITTLE BIT. I MEAN THERE'S BEEN LEGISLATION THAT ALLOWS PATENT PROTECTION THAT YOU KNOW GETS PEOPLE TO INCLUDE CHILDREN IN TRIALS THAT THEY MIGHT NOT HAVE OTHERWISE, BUT WE DON'T HAVE THAT WITH COGNITIVE IMPAIRMENTS PREGNANT WOMEN, THERE ARE LOTS OF COUNTER INCENTIVES I WOULD SAY, IN TERMS OF INCLUDING PEOPLE LIKE THAT DOESN'T MEAN WE SHOULDN'T THINK CREATIVELY ABOUT SWITCHING THE DEFAULT THAT THERE'S A DEFAULT IN SOME CASES ABOUT YOU KNOW AS SOMEBODY SAID BEFORE, YOU NEED TO GO TO THE IRB AND LET'S EXCLUDE THEM IN THIS CATEGORY, I THINK ASTERISKS EVERY LEVEL, WE SHOULD THINK ABOUT HOW TO SWITCH THAT DEFAULT AND WE MAY BE MORE OR LESS SUCCESSFUL WITHOUT OTHER KINDS OF INCENTIVES BUT THAT'S PART OF IT. YOU HAD ANOTHER COMMENT ABOUT THE IRB AND NOW I'M FORGETTING WHAT IT WAS? >> YEAH. >> YEAH. >> YEAH. >> [INDISCERNIBLE] WELL I THINK THAT'S A PROBLEM WE ARE NOT GOING TO SOLVE TODAY I THINK IRBs SOMETIME VS MIXED LOYALTYS AS GUESS HOW THEY IS IT AND I DON'T KNOW HOW TO DO THAT? >> SO CAN I PUSH BACK ON THIS A LITTLE BIT, TWO IRBs, ONE IN THE INSTITUTION AND THE UNIVERSITY AND THE AMERICAN ACADEMY OF PEDIATRICS OF IRB, I THINK THE IDEA THAT THE IRB ARE PRESENTING SUBSTANTIAL AMOUNT AND I'M NOT SURE THAT WAS NOT TRUE 20 YEARS AGO BUT I THINK AS YOU HAVE POINTED OUT THE LANDSCAPE HAS SHIFTED AND I THINK WITH APPROPRIATE PEDIATRIC EXPERTISE ON IRBs THAT'S WELL TAKEN INTO ACCOUNT. NOW I CAN'T SPEAK FOR EVERY IRB ACROSS THE COUNTRY BUT THERE ARE MANY, MANY MULTICENTER TRIALS THAT WE REVIEW THAT INCLUDE CHILDREN AND THEY'RE BEING APPROVED AT MULTIPLE PLACES SO I THINK THE IRB IS A BIT OF A BOOGIE MAN HERE AND I'M NOT QUITE SURE IT'S ENTIRELY WARRANTIED AT LEAST ON THE CHILDREN'S SIDE. I THINK, PREGNANCY IS STILL A CHALLENGE BUT ON CHILDREN, WE'RE DOING BETTER. >> THANK YOU FOR THAT. I AGREE WITH YOU AND I THINK ACTUALLY SOME OF DR. BIANCI'S DATA SUGGEST THAT THE PROBLEM IS NOT NECESSARILY EXCLUSION, IT'S ENROLLMENT ANALYSIS, YOU KNOW, IT COMES LATER. SO,--AND CERTAINLY THERE ARE DATA TO SUGGEST THAT YOU KNOW THE NUMBER OF PEDIATRIC TRIALS HAS GONE UP, THE NUMBER OF CHILDREN IN STUDIES HAS GONE UP SO ALL OF THAT IS WELL TAKEN. YEAH? >> ROGER WITH THE UNIVERSITY OF VERMONT. AS WE MOVE INTO BROADENING THE POPULATION AND MORE OF AN EFFECTIVENESS APPROACH OTHER NOVEL TRIAL DESIGNS ARE GOING TO BECOME OF GREATER INTEREST. PARTICULARLY CLUSTERED DESIGNS WHICH INCLUDE THESE BROAD POPULATIONS, ONE CAN IMAGINE A STUDY OF FALLS IN A NURSING HOME. AND YET, BECAUSE OF THE PERCEIVED VULNERABILITY, IRBs ARE PARTICULARLY LOATHE TO APPROVE MANY OF THESE TYPES OF STUDIES AND I WOULD HOPE THAT PART OF THIS WORKSHOP CAN ADDRESS THE ETHICAL ISSUES IN THOSE STUDIES AND PARTICULARLY AMPLIFY YOUR POINT HAVE HAVING MEMBERS OF THE INVOLVED GROUPS FULLY REPRESENTED. HARD TO SAY ON THE LOCAL LEVEL BUT PERHAPS IRBs LIKE THE AMERICAN PEDIATRIC ILW CAN HAVE FULL PRESENTATION TO HELP MOVE THESE STUDIES THROUGH. >> THANK YOU. >> I AM FROM NICHD, VERY NICE TALK. ONE OF THE ISSUES THAT MAY COME UP WOULD BE THE VULNERABILITY--WE HAVE TO DO TRIALS TO PATIENTS WHO HAVE EXTREMELY ILL AND UNLESS YOU DO THAT SPERKS LEECIAL I'M A NEOINATOLOGYST AND EVERY CONDITION IN WHICH WE DO A TRIAL FOR A NEW BORN BABY, ONE LEVEL OF PATIENT SO WHEN THE STATEMENT SAYS A PROSPECT FOR BENEFIT, I MEAN ONE WOULD NEVER CONSIDER DOING A TRIAL ON THIS FOR PROSPECT FOR BENEFIT THERE'S A RATIO BETWEEN THE BENEFIT AND WHAT ARE THE POTENTIAL HARMS AND THAT BECOMES A DIFFICULT THING TO MANAGE AND ONE STUDY WE HAD WAS OUR NETWORK DATA STUDY ON FETAL SURGERY FOR MILE O FILL AT 20 WEEKS JUST THINK THAT AND THAT AS A RISK ON ONE SIDE TO THE BABY PREMATURE BIRTH AT 20-22 WEEKS AND VERY, VERY BAD SITUATION AND ON THE MOTHER AND THE PROBLEM OF [INDISCERNIBLE] SO IT IS A QUESTION OF BALANCING THESE TWO AND AS OUR FRIEND FROM FDA JUST SAID, UNDER A TRIAL, ONE OF THE PATIENTS WERE MUCH BETTER CARED FOR THAN IF PEOPLE DO IT OUT IN THE LIMBO. ONCE EVERYTHING COMES OUT SO I THINK THAT KIND OF METHOD PROBABLY EMNATIVE AMERICANS IN THE NORTHERN FROM A MEETING LIKE THIS. >> ABSOLUTELY. I WILL GIVE ONE ANECDOTE. I HAD THE OPPORTUNITY TO BE PART OF THE PRESIDENT'S COMMISSION ON BIOETHICS AND ONE THING WE STRUGGLED WITH FOR ONE OF OUR REPORTS WAS DOING TRIALS OF ANTHRAX VACCINE IN CHILDREN, AND THE--THE DISCUSSION ABOUT DOING RESEARCH WITH PROTECTING CHILDREN FROM RESEARCH AND PROTECTING CHILDREN THROUGH RESEARCH WAS PART OF THAT DISCUSSION ALL THE WAY THROUGH THAT WE WILL NEVER KNOW WHAT TO DO IF WE HAVE ANN THRAKS ATTACK AND HOW TO--ANTHRAX ATTACK AND WHETHER TO VACCINATE CHILDREN UNLESS WE KNOW SOMETHING ABOUT THE VACCINE. BUT THERE'S LOTS OF RESISTANCE TO GIVING HEALTHY CHILDRENNAN TRACKS VACCINE WHEN WE DON'T EVEN KNOW IF ANTHRAX WILL EVER BE A PROBLEM IN THE UNITED STATES OR ANYWHERE, SO THERE'S THIS INTERESTING DEBATE ABOUT HOW YOU INCLUDE CHILDREN. AND I THINK ONE OF THE POINTS YOU MADE ABSOLUTELY, ALWAYS RISKS AND BENEFITS HAVE TO BE VERY CAREFULLY SORTED OUT AND NUANCED BUT I WOULD MAKE ONE DISAGREEMENT WITH SOMETHING YOU SAID AND THAT IS WE DO SOMETIMES DO RESEARCH THAT HAS NO PROSPECT OF BENEFIT. >> LAST QUESTION. >> LAST QUESTION. >> THANK YOU VERY MUCH. >> VULNERABILITIES IS ALWAYS THERE EVEN FOR AN ADULT POPULATION BECAUSE IN A NORMAL TREATMENT BEFORE YOU GO TO PHASE TWO, PHASE THREE TREATMENT, YOU DO PHASE ONE TREATMENTS SO [INDISCERNIBLE] VOLUNTEER WHY SHOULD I TAKE LIKE A HYPER TENSIVE SORE SOME MEDICATION, PEOPLE DO HAVE TO PARTICIPATE SO MY QUESTION TO YOU IS FROM YOUR GROUP, FROM YOUR OFFICE, WHAT'S YOUR RECOMMENDATION FOR INCLUSION FOR A NORMAL STUDY WHERE A CHILD DOESN'T HAVE ANY CONDITION, ANY CLINICAL CONDITION BUT WE WANT TO UNDERSTAND THE ABSORPTION, WE DISTRIBUTION METABOLISM BECAUSE THOSE THINGS ARE NECESSARY TO DEVELOP MEDICATION FOR THE DISEASE CONDITIONS SO I WONDER WHAT'S YOUR RECOMMENDATION FOR THIS WORLD GROUP FOR THOSE STUDIES? >> I DON'T KNOW IF I SHOULD SAY IT'S MY RECOMMENDATION, THE REGULATIONS WE LIVE UNDER GIVES VERY SPECIFIC GUIDANCE ABOUT THAT. AND YOU KNOW INCLUDING HEALTHY NORMAL CHILDREN IN STUDIES IS ACCEPTABLE IF THE RISK IS QUITE LOW. SO YOU CAN'T--I MEAN THIS IS WHAT I MENTIONED BEFORE ABOUT THE CATEGORY OF GREATER THAN--IN THE CHILDREN'S REGS IT'S GREATER THAN A MINOR INCREMENT OF MINIMAL RISK THAT'S NOT JUSTIFIED BY A BENEFIT. THAT CATEGORY IS VERY HARD TO GET TO JUSTIFYING IT APPROVED BUT-- >> BUT SOMETIMES PUTTING KIDS IN STUDIES WHERE THE RISK IS EITHER MINIMAL OR A MINOR INCREMENT IS PERFECTLY ALLOWABLE. >> THAT'S THE REASON WE ARE HERE BECAUSE WE'RE NOT ABLE TO MAKE PROGRESS ON THAT. >> YEAH. SO I THINK--WELL WE CAN TALK ABOUT IT IN THE WORKSHOP. [ APPLAUSE ] >> SO BEFORE WE BRING UP THE NEXT SPEAKERS WHO ARE THE CO-CHAIRS OF THE STEERING COMMITTEE OF THE PLANNING GROUP, I WANT TO ACKNOWLEDGE THE PLANNING GROUP FOR IF WORKSHOP. DR. BERNARD AND I CO-CHAIR THE INCLUSION COMMITTEE AND THIS GROUP HAS BEEN FANTASTIC. THEY ORGANIZED THIS MEETING IN SHORT NOTICE AND THERE'S I SMALLER SUBCOMMITTEE OR STEERING COMMITTEE WITH THIS GROUP, DR. JANEAT KIN SON AND DR. SUMEER ARE THE CO-CHAIRS AND I WANT TO ACKNOWLEDGE THEM AND LISA, AND TYRONE AND JIM GRIFFIN PLEASE JOIN ME IN THANKING THEM. [ APPLAUSE ] IS SAMERE AND JANE? >> SO WE'RE JUST GOING TO GIVE INSTRUCTIONS BECAUSE WE KNOW EVERYBODY NEEDS TO TAKE A BREAK TOO. WE'VE BEEN HERE FOR A COUPLE OF HOURS. THERE ARE FOUR WORK GROUPS, ONE, TWO, THREE, AND FOUR. AND I BELIEVE ON THE BADGE, YOU SHOULD HAVE AN INDICATION OF WHAT WORK GROUP YOU'RE ON. >> IF YOU DON'T HAVE A WORK GROUP THAT YOU WOULD LIKE TO JOIN, PLEASE LET US KNOW IN THE FRONT WHICH ONE YOU WOULD LIKE--EXCEPT FOR GROUP ONE I THINK WE ARE AT CAPACITY FOR ONE. >> IS THAT RIGHT? KASP A R--CAPACITY? >> AND WE HAVE JERON WHO WAS THE REAL POWER HOUSE IN OUR WORK GROUP. [ APPLAUSE ] IN OUR GROUP. YOU SHOULD HAVE--THOSE OF YOU WHO WERE ON THE CALLS, YOU SHOULD HAVE RECEIVED THE MINUTES AND SOME DRAFT REPORTS FROM THE FIRST THREE CALLS THAT WE HAD. FOR THOSE OF YOU WHO HAVE ALREADY BEEN PARTICIPATING IN THE WORK GROUP, YOU WILL BE JOINED BY ABOUT 15 NEW MEMBERS WHO REGISTERED TO COME SO WE'LL HAVE NEW PEOPLE IN THE GROUP AND THEY HAVE CHOSEN THE WORK GROUPS BASED ON THEIR EXPERTISE. YOU HAVE TWO HOURS FOR ADDITIONAL DISCUSSIONS. TO INCORPORATE COMMENTS FROM THE NEW MEMBERS AND ANY ADDITIONAL THOUGHTS YOU MAY HAVE COME UP WITH DURING THESE PLENARY TALKS AND WE WILL PROVIDE AN INDIVIDUAL TO TAKE MINUTES AND ALSO FACILITATOR TO HELP MAKE THE SLIDES FOR TOMORROW'S REPORT OUT. AND LET'S SEE, WORK GROUP ONE, YOU GO TO ROOM A. >> THAT WAY. >> IT'S, OKAY? WORK GROUP TWO, YOU GO TO ROOM G, LIKE GO. WORK GROUP THREE, YOU GO TO ROOM B LIKE BOY. AND WORK GROUP FOUR, GOES TO WORK C, LIKE CAT. AND FOR THOSE THAT ARE PARTICIPATING BY VIDEOCAST, THIS ENDS THE VIDEOCAST FOR TODAY. >> IT WILL START BACK TOMORROW AT EIGHT. >> YESES, AT EIGHT. >> THANK YOU. >> THANK YOU. [ APPLAUSE ] >> SO WE WILL START AT 3:00.