>> WELCOME TO THE INCLUSION ACROSS THE LIFE SPAN II WORKSHOPS IMPLEMENTATION OF FUTURE DIRECTIONS. WE WILL BEGIN THE WORKSHOP WITH DR. MARIE BERNARD, DEPUTY DIRECTOR, NATIONAL INSTITUTE ON AGING. >> HELLO, I'M MARIE BERNARD, DEPUTY DIRECTOR OF THE NATIONAL INSTITUTE ON AGING AND CO CHAIR TRANSNIH GOVERNANCE AND INCLUSION COMMITTEE. I HAVE THE PRIVILEGE OF WELCOMING TODAY THROUGH THE CULMINATION OF SEVERAL MONTHS OF PREPARATION AND YEARS OF DELIBERATION AND EFFORT AT NIH TO INSURE APPROPRIATE INCLUSIONS OF POPULATIONS IN NIH FUNDED CLINICAL RESEARCH. NEXT. THIS PARTICULAR WORKSHOP CAME ABOUT AS AN OFFSHOOT OF SOME OF THE PROVISIONS OF THE 21st CENTURY CURES ACT. THE ACT PASSED IN DECEMBER OF 2016, CALLED FOR NIH TO REEXAMINE ITS POLICIES REGARDING INCLUSION BY AGE. AS PART OF THAT PROCESS, WE WERE MANDATED TO MOVE A SCIENTIFIC CONFERENCE TO CONSIDER THE ISSUE OF AGE INCLUSION. NEXT. THUS, IN JUNE OF 2017, WE HELD A WORKSHOP TO CONSIDER THE CHALLENGES AND OPPORTUNITIES FOR INCLUDING CHILDREN AND OLDER ADULTS IN CLINICAL RESEARCH. THIS INCLUDED STRATEGIES THAT WOULD PRODUCE MORE AGE-INCLUSIVE CLINICAL STUDIES. NEXT. FOLLOWING THAT WORKSHOP THERE WAS SIGNIFICANT NIH DELIBERATION, INPUT FROM MULTIPLE OTHER SOURCES AND A DECISION TO REVISE THE NIH CHILD INCLUSION POLICY TO BECOME THE INCLUSION ACROSS THE LIFE SPAN POLICY TO ADDRESS INCLUSION AT BOTH ENDS OF THE AGE EXPECT RUM. THE POLICY WAS ANNOUNCED IN DECEMBER 2017 AND BECAME EFFECTIVE WITH APPLICATIONS SUBMITTED IN JANUARY 2019. NEXT. WHAT DOES THE POLICY CALL FOR? YOU MUST NOW SUBMIT A PLAN FOR INCLUDING INDIVIDUALS ACROSS THE LIFE SPAN, INCLUDING CHILDREN AND OLDER ADULTS. IF YOU ARE EXCLUDING BASED ON AGE, YOU MUST PROVIDE A SCIENTIFIC JUSTIFICATION FOR THE AGE RANGE YOU'RE TARGETING. THERE ARE ACCEPTABLE REASONS TO EXCLUDE SOME GROUPS. FOR EXAMPLE, THERE IS LITTLE TO NO SCIENTIFIC JUSTIFICATION TO HAVE 6 YEAR-OLDS IN LATE ONSET ALZHEIMER'S STUDIES OR JUVENILES IN AN ARTRITIS STUDY. THESE INCLUSION ISSUES ARE ADDRESSED IN WRITTEN CRITIQUES. ADDITIONALLY THE POLICY CALLS FOR PROGRESS REPORTS THAT PROVIDE ANONYMIZED INDIVIDUAL LEVEL DATA ON AGE OF ENROLLMENT, IN UNITS RANGING FROM AS LITTLE AS HOURS AS MUCH AS YEARS, SEX AND GENDER AND RACE AND ETHNICITY. THIS WILL ENABLE NIH FOR THE FIRST TIME TO EXAMINE THE ADEQUACY AND INCLUSION ACROSS A WIDE RANGE OF DISEASE STATES, WITH THE NEW ABILITY TO SORT THE DATA ACCORDING TO WHAT IS APPROPRIATE FOR THE SCIENTIFIC QUESTION YOU'VE BEEN ASKED. NEXT SLIDE. SO WHAT ARE THE GOALS OF THIS WORKSHOP? WE AIM TO SHARE EVIDENCE-BASED APPROACHES TO FACILITATE COMPLIANT WITH THE SPIRIT OF THE IALL POLICY. IT'S QUITE FRANKLY EASY TO SAY THAT YOU'RE SIMPLY NOT GOING TO EXCLUDE PEDIATRIC OR OLDER ADULT POPULATIONS, IT'S MUCH MORE DIFFICULT TO INCLUDE THOSE POPULATIONS IN A MOVEABLE FASHION AND THERE ARE CHALLENGES IN MEANINGFUL INCLUSION ACROSS THE LIFE SPAN OF BEARING POPULATIONS THAT WILL RECEIVE ATTENTION DURING THIS MEETING. THERE WILL BE OPEN SCIENTIFIC DISCUSSION FOR THOSE EVIDENCE-BASED SUGGESTIONS AND THERE WILL BE THE OPPORTUNITY TO SHARE RESOURCES TO FACILITATE INCLUSION ACROSS THE LIFE SPAN. THE VIDEOTAPES THAT ARE ALREADY AVAILABLE TO YOU AS WELL AS THE WORKHOP SUMMARY AND PEER REVIEW PAPERS WILL COME THROUGH THE WORKSHOP. NEXT SLIDE. SO WHAT IS TODAY'S AGENDA LOOK LIKE? WE START WITH GREETINGS FROM NIH SENIOR LEADERSHIP WITH DR. FRANCIS COLLINS THE NIH DIRECTOR WE THEN DEVOTE MORE CONCENTRATED TIME DEVOTED TO THE NLM AND THE CLINICAL.GOV AND THE NIH GRANT REVIEWS. I THEY WILL TALK ABOUT WHAT'S BEING DONE FOR FULL IMPLEMENTATION OF THE IALL POLICY. WE WILL THEN HAVE A SERIES OF PANELS THAT WILL ADDRESS THE SPECTRUM OF CONSIDERATIONS TO FACILITATE APPROPRIATE INCLUSION. NEXT SLIDE. THESE PANELS INCLUDE INCLUSION AND EXCLUSION CRITERIA, STUDY DESIGN AND METRICS, RECRUITMENT, ENROLLMENT AND RETENTION AND DATA ANALYSIS AND STUDY INTERPRETATION, NEXT. VERY IMPORTANTLY EVERY SESSION IS CONFIGURED TO ALLOW SCIENTIFIC DISCUSSION. PLEASE DO NOT HESITATE TO USE THE CHAT BOX TO CONTRIBUTE YOUR THOUGHTS AND QUESTIONS. ALTHOUGH WE MAY NOTHING LIKE THAT BE ABLE TO GET TO EVERY POINT RAISED, THE INPUT FROM THE CHAT AS WELL AS RESPONSE FROM THE VIDEO PRESENTATIONS WILL BE CONSIDERED AS WORKSHOP SUMMARY AND OTHER PUBLICATIONS ARE DEVELOPED. NEXT SLIDE. FINALLY NIH WOULD LIKE TO THANK THE PANELISTS WHO CONTRIBUTE THEIR EXPERTISE AND TIME TO THIS EFFORT, THEY'RE A DEDICATED GROUP WHO PUT A LOT OF TIME AND ENERGY INTO DEVELOPING WHAT WE BELIEVE WILL BE A VERY ENGAGING DISCUSSION. THANK YOU. >> WE WILL NOW HAVE GREETINGS FROM THE N NIH LEADERSHIP. >> WELCOME TO THE INCLUSION ACROSS THE LIFE SPAN WORKSHOP. PART 2. I'M FRANCIS COLLINS, DIRECTOR OF THE NATIONAL INSTITUTES OF HEALTH, I HAVE THE PLEASURE OF WELCOMING ATTENDEES TO THE FIRST WORKSHOP BACK IN 2017. THAT 1 OF COURSE, WE WERE ABLE TO MEET IN PERSON, BUT COVID-19 HAS CHANGED SO MANY THINGS IN OUR EXPERIENCES AND I'M SPEAKING TO YOU NOW FROM MY HOME OFFICE IN CHEVY CHASE, MARYLAND AND OF COURSE THE WORKSHOP ITSELF HAS 1 THAT I THINK WILL BE VERY SIGNIFICANT AND I HOPE WILL BE MEANINGFUL TO ALL OF YOU WHO HAVE A CHANCE TO TAKE PART. THIS NOTION OF THE NEED TO BE INCLUSIVE ACROSS THE LIFE SPANS COULD HARDLY BE MORE CLEAR RIGHT NOW IN THE CONTEXT OF COVID-19. IF WE WERE TO IGNORE AT THE PRESENT TIME THE VARIATION IN WHAT HAPPENS AFTER EXPOSURE TO THIS VIRUS, DEPENDING ON MANY DIFFERENT PARAMETERS, AGE, GENDER, SOCIOECONOMIC STATUS, RACE AND ETHNICITY, ALL OF THOSE THINGS, WE WOULD BE MISSING A HUGE AMOUNT OF THE MESSAGE THAT WE NOW NEED TO ACT UPON. WE KNOW THIS IS A DISEASE THAT PARTICULARLY AFFLICTS THE ELDERLY SO IF WE WERE FAILING TO STUDY FOR INSTANCE A VACCINE'S EFFECT TO PROTECT THE ELDERLY, WE WOULD MISS 1 OF THE MOST IMPORTANT SIGNALS WE NEED TO SEE. LIKEWISE WE KNOW THIS DISEASE PARTICULARLY HITS PEOPLE WITH CHRONIC ILLNESSES, WE KNOW IT SEEMS TO BE A LITTLE MORE SEVERE CERTAIN POPULATIONS AND MOSTLY BECAUSE THEY'RE NOT IN A GOOD POSITION TO BE ABLE TO SHELTER AT HOME WHERE OUR BEST SUBLICK HEALTH MEASURES ARE SIMPLY NOT AVAILABLE FOR THOSE WHO NEED TO BE IN A DIFFERENT PLACE AND CAN'T NECESSARILY TAKE ADVANTAGE OF SOCIAL DISTANCING IN ORDER TO PROTECT THEMSELVES. SO WE HAVE A LOT TO LEARN, AND THEN CHILDREN. WE FOR A WHILED SAID CHILDREN WERE PROBABLY NOT TOO MUCH TO BE WORRIED ABOUT BECAUSE WHILE THEY COULD GET INFECTED THEY SEEM TO DO FAIRLY WELL AND THEN THIS NEW CONDITION CALLED MIS-C, MULTIINFLAMMATORY SYNDROME OF CHILDREN, WHICH DOESN'T SEEM TO BE SO MUCH A DIRECT CONQUENCE OF THE VIRUS BUT POST INFECTIOUS VASC LOPATHY THAT COMES ALONG AND STILL DESPERATELY NEEDS TO BE UNDERSTOOD AND NIH IS DOING A LOT OF WORK TO FIGURE THIS OUT. IS IT AN AUTOIMMUNE PHENOMENON PRODUCED BY THE VIRAL INFECTION? IT CAN BE QUITE SEVERE AND HAS AFFECTED HUNDREDS AND HUNDREDS OF CHILDREN. IF 1 NEEDED A LESSON ABOUT THE IMPORTANCE OF INCLUSIVENESS ACROSS THE LIFE SPAN COVID-19 GIVES YOU THAT IN A VERY DRAMATIC WAY. SO, WE NEED TO CONSIDER IN THE COURSE OF THIS WORKSHOP WHAT MORE MIGHT WE DO TO BE ABLE TO BUILD STRENGTH IN THIS AREA. CLINICAL TRIALS ARE A DEFINING THAT'S HOW WE COLLECT EVIDENCE BUT IN ORDER TO HAVE THAT EVIDENCE OF GREATEST UTILITY WE NEED TO BE INSURING THAT ALL COMMUNITIES ARE TAKING PART SO THEY CAN BENEFIT EQUALLY FROM THOSE MEDICAL ADVANCES. NIH HAS INSTITUTED POLICIES OVER THE YEARS TO INSURE THAT PARTICIPANTS IN CLINICAL TRIALS ARE IN FACT REPRESENTATIVE OF PATIENT POPULATIONS, WE'RE IN THE MIDDLE OF DOING THAT RIGHT NOW AS WE SEEK TO ROLL OUT THE VACCINE TRIALINGS AGAINST COVID-19. WE WANT TO BE SURE THAT THE PARTICIPANTS IN THOSE TRIALS ARE REPRESENTATIVE OF THE GROUPS, PARTICULARLY THOSE THAT HAVE HAD THE MOST SIGNIFICANT HARMS FROM THIS VIRUS. SO IT IS THE ESSENCE OF SCIENCE TO DO THESE THINGS AND IT'S FAIR TO SAY, THAT OVER THE COURSE OF SEVERAL DECADES, NIH HAS GOTTEN BETTER AND BETTER AT ADDRESSING THIS INCLUSIVE INNOCENCE BUT I THINK IT'S ALSO FAIR TO SAY, WE'RE NOT COMPLETELY THERE YET, HENCE THE IMPORTANCE OF THIS WORKSHOP. JUST GOING BACK OVER THE HISTORY, CERTAINLY IN THE 1980S AND 1990S, BACK AT A TIME WHERE MANY CLINICAL TRIALS WERE RUN MOSTLY ON WHITE MEN, WE WERE BROUGHT TO REALIZE A LITTLE HELP WITH MEMBERS OF THE CONGRESS AND OTHERS THAT THAT WAS REALLY NOT THE RIGHT WAY TO DO THINGS SO WE EXTENSIVELY EXPANDED OUR CAPABILITIES TO ENROLL WOMEN IN A MINORITY POPULATIONS OVER THE COURSE OF A COUPLE OF DECADES; NOT TO SAY THAT EVERY SINGLE TRIAL ACHIEVES THAT BUT CERTAINLY ACROSS THE BOARD FOR INSTANCE MORE THAN HALF OF THE PARTICIPANTS IN NIH CLINICAL TRIALS ARE NOW WOMEN AND THEN WITH CHILDREN, NIH ISSUED A POLICY REQUIRING INCLUSION OF CHILDREN IN 1998. 2015 THAT DEFINITION WAS REVISED TO BE CHILDREN UNDER 18 BECAUSE A LOT OF, WHAT PEOPLE WERE CALLING PARTICIPATION BY CHILDREN WAS ACTUALLY ANY INDIVIDUALS WHO COULD ALREADY VOTE AND I DON'T THINK THAT WAS THE INTENTION OF THE EFFORT AND THEN THE 21st CENTURY CURES ACT CAME LONG SIGNED INTO LAW DECEMBER 2016 PROVIDING A BIG BOOST TO OUR EFFORTS, REQUIRING NIH TO CONSIDER WHETHER WE SHOULD DO MORE IN TERMS OF OTHER POLICIES TO INSURE INCLUSION OF REPRESENTATIVE GROUPS IN CLINICAL STUDIES BY AGE. AND IT HELPED NIH TO BE ABLE TO DO THAT BY THE CONVENING OF A WORKSHOP AND SO THAT WAS THE INCLUSION ACROSS THE LIFE SPAN PART 1 WORKSHOP BACK IN 2017, IT WAS A VIGOROUS DISCUSSION ABOUT OPPORTUNITIES AND CHALLENGES AND PARTICULARLY ABOUT CHILDREN AND OLDER ADULTS AND IDENTIFIED SOME STRATEGIES THAT WOULD BE AMENABLE TO BEING MORE INCLUSIVE ABOUT AGE, TO SENSITIVE CLINICAL STUDIES. EVIDENCE OF ITS SUCCESS, WELL, WE CHANGED THE INCLUSION POLICY IN DECEMBER 2017 AND THAT BECAME A REQUIREMENT EFFECTIVELY JANUARY 2019. SO FOR THE LAST YEAR AND HALF, THIS INCLUSION HAS FOUND ITS WAY INTO OUR EXPECTATIONS OF OUR CLINICAL TRIALS IN A MUCH MORE SPECIFIC WAY. SO WHY DO WE NEED THIS WORKSHOP, WELL, I THINK AS I SAID A LITTLE BIT AGO, WE MADE PROGRESS BUT WE STILL HAVE THINGS WE CAN DO BETTER, SO THE WORKSHOP AIMS TO HELP RESEARCHERS, TO USE EVIDENCE-BASED APPROACHES TO BE FULLY COMMRI APT WITH THIS NEW POLICY, IT WILL FEATURE PRESENTATIONS, HOW BEST TO DEPLOY ALL OF THESE THINGS SUCH AS INCLUSION, EXCLUSION, CRITERIA, WHAT SHOULD THOSE BE? WHEN YOU HAVE HAD KIND OF INCLUSIVE APPROACH, ARE YOU DOING YOUR DATA,AINAL SIS IN A WAY THAT YOU'RE LEARN FREE RADICALS GENERATED THE CRITICAL DIFFERENCES THAT MIGHT APPEAR DEPENDING ON AGE AND OTHER PARAMETERS OF YOUR PARTICIPANTS. SO WE HOPE THIS WORKSHOP WILL BE USEFUL TO ALL THOSE WHO STRIVE TO INCLUDE UNDER REPRESENTED POPULATIONS, AGAIN I CAN'T SAY ENOUGH ABOUT HOW THE EXPERIENCE RIGHT NOW IN 2020 WITH THERAPEUTIC AND VACCINE TRIALS FOR COVID-19 MAKE IT SO CRITICALLY CLEAR AND IMPORTANT THAT WE NEED TO DO THIS. AND HOPEFULLY, WHAT COMES OUT OF THIS WORKSHOP WILL FURTHER ABOUT THE WAYS TO DO THIS BOOF THE.--BEST, SO I WANT TO THANK EVERYBODY ACROSS THE NIH WHO HELPED BRING THIS WORKSHOP TOGETHER, ESPECIALLY MARIE BERNARD AND I WISH ALL OF YOU DESPITE THE VIRTUAL SETTING AN OPPORTUNITY FOR INTERESTING DISCUSSIONS, BRAINSTORMING ABOUT BETTER WAYS TO CARRY OUT OUR RESPONSIBILITY FOR INCLUSION ACROSS THE LIFE SPAN AND A TIMELY OUTCOME THAT WILL CONTINUE TO MAKE OUR CLINICAL TRIALS EVEN BETTER. SO WITH THAT, AND WITH BEST WISHES FOR A SUCCESSFUL SYMPOSIUM, I'M GOING TO HAND THIS OFF TO WHOEVER THE NEXT SPEAKER IS, WISHING YOU ALL THE BEST. >> THANK YOU, THANK YOU DR. COLLINS AND I'M MIKE LAUER, I'M THE DEPUTY DIRECTOR OF NIH FOR EXTRAMURAL RESEARCH AND I'M THE DIRECTOR OF THE OFFICE OF EXTRAMURAL RESEARCH. I WOULD LIKE TO TAKE THIS OPPORTUNITY TO WELCOME YOU TO THIS WORKSHOP. I REMEMBER THE PREVIOUS WORKSHOP AND HAVING THE OPPORTUNITY TO MEET YOU, I THINK WE WERE IN A BIG ROOM IN NATCHER. I WANT TO CONGRATULATE DR. BERNARD AND HER COLLEAGUES FOR PUTTING ON AN ABSOLUTELY OUTSTANDING PROGRAM. SLIDE 214 HAS THE NAMES OF THE PEOPLE WHO WERE ON THE PLANNING COMMITTEE AND I WOULD LIKE TO CALL THEM OUT FOR OUTSTANDING WORK IN PLANNING AND PUTTING THIS EVENT TOGETHER. WITHIN THE OFFICE OF EXTRAMURAL RESEARCH, DAWN CORBETT, WHO IS OUR INCLUSION POLICY OFFICER HAS PLAYED A MAJOR ROLE IN HELPING MAKE ALL THIS HAPPEN. THE OFFICE OF EXTRAMURAL RESEARCH IS RESPONSIBLE FOR IMPLEMENTING MUCH OF THE CORPORATE INFRASTRUCTURE BY WHICH INCLUSION POLICIES CAN BE INCORPORATED. WE'RE ALSO RESPONSIBLE FOR COMPLIANCE AND OVERSIGHT OF PEER REVIEW, YOU WILL HEAR QUITE A BIT ABOUT THAT, I SEE IT LATE OR TODAY AND SO IT'S BEEN A GREAT PLEASURE FOR US TO WORK WITH DR. BERNARD AND WORK WITH THE INCLUSION GOVERNANCE COMMITTEE, TO WORK WITH THE PLANNING COMMITTEE ON THINKING ABOUT THESE ISSUES. I WANT TO CONGRATULATE YOU ON PUTTING TOGETHER AN OUTSTANDING WORKSHOP. I THINK DR. COLLYNN'S COMMENTS ARE SPOT ON ABOUT HOW INCREDIBLY IMPORTANT INCLUSION ALWAYS HAS BEEN AND EVEN MORE SO NOW AS WE'RE DEALING WITH COVID AND LOOK FORWARD TO AN INTERESTING AND EXCITING DAY OF A LOT OF WORK. THANK YOU. >> GOOD MORNING I'M RICHARD HODES, DIRECTOR OF THE NATIONAL INSTITUTE ON AGING. I WOULD LIKE TO ADD MY WELCOME AS WELL. AS FRANCIS EMPHASIZED THERE COULD BE NO MORE POIGNANT TIME FOR EXPANDING INCLUSION ACROSS THE LIFE SPAN OF THIS MEETING AND A BROADER DIMENSION OF INCLUSION ACROSS ALL OF OUR EFFORTS. NATION ADDED INSTITUTES ON AGING AND CHILD AND HUMAN DEVELOPMENT ARE FOCUSED ON DIFFERENT PARTS OF THE LIFE SPAN AND YET WE RECOGNIZE FOR SOMETIME THE INEXPLICABLE RELATIONSHIP BETWEEN THE 2. EEIVETS EARLY IN LIFE, AFFECTING LATE AND THIS HAS BECOME A MISSION NOT JUST FOR INSTITUTES BUT ACROSS ALL OF NIH AND FOR ALL OF US. THE IMPORTANCE OF INCLUSION IS ILLUSTRATIVE OF AT LEAST 2 LEVELS, FIRST IN TERMS OF THE SCIENCE ITSELF. FOR US TO CARRY OUT OUR MISSION OF UNDERSTANDING THE BASIC BIOLOGY AND BEHAVIOR THAT UNDERLIES HUMANS AND OUR ABILITY TO TRANSLATE THAT UNDERSTANDING AND TO PRACTICAL INTERVENTIONS, IT'S CRITICAL THAT WE CARRY OUT RESEARCH THAT UNDERSTANDS THE MANIFESTATIONS OF LIFE SPAN AND LITTLER ASPECTS OF DIVERSITY ON THAT WORK. AND ULTIMATELY OF COURSE THE OTHER DIMENSION IS THAT ALL OF THIS RESEARCH IS INTENDED TO PROFIT, ADVANTAGE THE HEALTH, WELL BEING, QUALITY OF LIFE FOR AMERICANS FOR CITIZEN OF THE WORLD, WHO THEMSELVES ARE DIVERSE AND ONLY BY INCLUDING DIVERSITY ACROSS AGE AND OTHER DIMENSIONS OF OF DEMOGRAPHICS ARE WE GOING TO BE ABLE TO ACHIEVE THAT GOAL. SO I ADD MY THANKS AND APPRECIATION TO ALL OF YOU FOR THE WORK YOU HAVE DONE, WILL BE DOING AND LOOKING FORWARD TO AN INTERESTING DAY AND PERHAPS MOST IMPORTANT, PERHAPS THE OUTCOME. >> HELLO EVERYONE, I WOULD WOULD LIKE TO JOIN MY COLLEAGUES IN WELCOMING ALL THE PARTICIPANTS TO TODAY'S WORKSHOP, WHEN NEW POLICIES ARE ESTABLISHED, IT'S VITAL TO CHECK IN ON HOW IMPLEMENTATION OF THOSE POLICIES IS PROCEEDING, WHAT OBSTACLES MAY HAVE BEEN ENCOUNTERED AND ANY FURTHER ACTIONS THAT MIGHT BE NEEDED TO CARRY OUT THE FULL INTENT OF THOSE POLICIES. THIS IS CERTAINLY THE CASE WITH NIH'S POLICY TO INSURE THAT PARTICIPANTS ACROSS THE LIFE SPAN ARE INCLUDED IN CLINICAL RESEARCH. JUST OVER THE PAST 6 MONTHS, WE'VE OBSERVED A VERY CLEAR EXAMPLE OF HOW IMPORTANT IT IS TO INCLUDE ALL OF OUR POPULATIONS IN THE SEARCH. THE COVID-19 PANDEMIC HAS AFFECTED EVERYONE BUT SOME POPULATIONS ARE EXPERIENCING BOTH THE EFFECTS MORE ACUTELY THAN OTHERS. WE HAVE SO MUCH MORE TO LEARN ABOUT IMMEDIATE AND LONG-TERM RISKS TO CHILDREN AND PREGNANT WOMEN, BOTH OF WHOM ARE HISTORICALLY UNDERREPRESENTED IN CLINICAL TRIALS. AND UNTIL RECENTLY AN EPIDEMIOLOGICAL STUDIES OF COMMUNITY INFECTION AND TRANSMISSION RATES. THIS IS EXTREMELY IMPORTANT AS CASES OF COVID-19 IN CHILDREN ARE RISING DRAMATICALLY AND WE NEED DATA AND EVIDENCE TO ADDRESS CRUCIAL QUESTIONS, SUCH AS WHETHER IT IS SAFE FOR CHILDREN ANDA ADOLESCENTS TO RETURN TO SCHOOL. FOR DECADES CHILDREN WERE THOUGHT OF AS LITTLE ADULTS, THEREFORE IT WASN'T NECESSARY TO SPECIFICALLY INCLUDE THEM IN RESEARCH. AS WE LEARNED MORE ABOUT HUMAN DEVELOPMENT, IT BECAME CLEAR THAT CHILDREN MUST BE INCLUDED UNLESS THERE'S A SCIENTIFIC OR ETHICALLY VALID REASON NOT TO. MORE OVER, GIVEN THE SIGNIFICANT PHYSIOLOGIC CHANGES THAT OCCUR FROM BIRTH THROUGH THE DIFFERENT STAGES OF CHILDHOOD AND INTO ADOLESCENTS AND YOUNG ADULTHOOD, COLLECTING DATA FROM RESEARCH STUDIES THAT INCLUDE PARTICIPANTS ACROSS THE LIFE SPAN BECOMES EVEN MORE CRITICAL. MOVING FORWARD IT'S NOW TIME TO COLLECT SIMILAR DATA ON OTHER SO CALLED SPECIAL POPULATIONS. NICHD HAS BEEN PLEASED TO LEAD THE FEDERAL TASK FORCE ON RESEARCH IN PREGNANT WOMEN AND LACTATING WOMEN. THE INITIAL CHARGE TO THIS CONGRESSALLY MANDATED TASK FORCE WAS TO MAKE RECOMMENDATIONS TO THE HHS SECRETARY TO SAFELY INCLUDE PREGNANT AND LACTATING WOMEN INTO CLINICAL STUDIES. FIFTEEN RECOMMENDATIONS WERE MADE AND SUBMITTED TO HHS SECRETARY AZAR LAST FALL. DURING THE PAST YEAR THE TASK FORCE HAS BEEN WORKING ON HOW BEST TO IMPLEMENT THE RECOMMENDATIONS, A FINAL REPORT WILL GO TO SECRETARY AZAR IN A FEW WEEKS. YOU WILL HEAR MORE ABOUT THIS FROM A SPEAKER LATER IN THE PROGRAM, DR. GEORGE SADE WHO IS A LEADING VOICE IN THIS AREA. OTHER GROUPS THAT HAVE NOT BEEN ROUTINELY INCLUDED IN RESEARCH ARE THOSE WITH INTELLECTUAL, DEVELOPMENTAL OR PHYSICAL DISABILITIES. I'M PLEASED TO SAY THAT THE NICHD FUNDED PEDIATRIC TRIALS NETWORK IS NOW CONDUCTING CLINICAL RESEARCH THAT SPECIFICALLY INCLUDES PEOPLE WITH DOWNS SYNDROME, AS WELL AS TRAINING RESEARCHERS ON HOW TO WORK WITH INDIVIDUALS WITH DOWNS SYNDROME AND THEIR FAMILIES. YOU MAY HEAR MORE ABOUT THESE EFFORTS FROM DR. DANNY BENJAMIN LATER TODAY. WE'RE ALSO USING AN EXISTING NICHD FUNDED NETWORK TO EXAMINE THE EFFECTS OF COVID-19 ON PREGNANT WOMEN AND THEIR OFFSPRING. SO ON BEHALF OF THE NICHD, I WOULD ONCE AGAIN LIKE TO THANK THE ORGANIZERS FOR ARRANGING THIS MEETING AND I LOOK FORWARD TO LEARNING MORE ABOUT THE INCLUSION OF ALL OF OUR POPULATIONS IN RESEARCH. THANK YOU. >> GOOD MORNING, I'M JANINE CLAYTON, NIH ASSOCIATE DIRECTOR FOR RESEARCH AND WOMEN'S HEALTH AND DIRECTOR OF THE NIH OFFICE OF RESEARCH AND HEALTH AND I HAVE THE OPPORTUNITY TO SHARE THIS COMMITTEE WITH DR. MARIE BERNARD. WE'RE FORTUNATE TO HAVE SPEAKERS SUCH EXTRAORDINARY BACKGROUND AND ACHIEVEMENT AND I WOULD LIKE TO THANK THEM PERSONALLY, NOT ONLY FOR THEIR PARTICIPATION BUT ALSO FOR THEIR COMMITMENT TO INCLUSION. WE AT THE OFFICE OF RESEARCH AND WOMEN'S HEALTH LIKE TO SAY THAT INCLUSION IS IN OUR DNA AND IN FACT WE'RE CELEBRATING AN IMPORTANT ANNIVERSARY. THIRTY YEARS AGO THIS MONTH CONGRESS IN RESPONSE TO CONCERNS RAISED BY SCIENTISTS, WOMEN AND POLICY MAKERS ABOUT GAPS IN WOMEN'S HEALTH RESEARCH, INCLUDING THE IS FOR MAKING WOMEN PROPERTILY INCLUDED IN TODAYS SUPPORTED BY THE NIH. AS DR. COLLINS NOTED, INCLUSION IS THE ESSENCE OF SCIENCE. BY INSURING THAT TRIAL PARTICIPANTS ARE REPRESENTED AT THE POPULATIONS AFFECTED BY THE DISEASE AND BEING STUDIED, RESEARCHERS CAN ACCOMPLISH THE GOALS OF THE STUDY. THIS IS IN THE BEST INTEREST OF SCIENCE, THE POPULATIONS AFFECTED BY THE CONDITIONS BEING STUDIED AND TAXPAYERS. WE KNOW FROM EXPERIENCE, JUST HOW IMPORTANT THIS IS, AND HOW RELEVANT. FOR EXAMPLE, WE KNOW THAT WHILE WOMEN LIVE LONGER THAN MEN, OLDER WOMEN HAVE MORE CO-MORBIDITIES WHICH IRONICALLY HAS RESULTED IN THEM BEING EXCLUDE FRIDAY CLINICAL TRIALS FOR CHRONIC DISEASES AFFECTING WOMEN. BUT INCLUSION ALONE GETS YOU ONLY SO FAR. THE RESULTS ALSO MUST BE AGGREGATED BY SEX, ANALYZED AND REPORTED APPROPRIATELY. TOWARD THAT END IMPORTANT PROGRESS WILL BE MADE BECAUSE OF THE 21st CENTURY CURES ACT REQUIREMENT THAT APPLICABLE PHASE 3 CLINICAL TRIALS SUBMIT STRATIFIED ANALYSIS BY SEX, GENDER, RACE AND ETHNICITY TO THE WEBSITE CLINICALTRIALS.GOV. AS SCIENTISTS WE KNOW THE DEMANDS ON BIOMEDICAL RESEARCH ARE EVER-EVOLVING, WHETHER IT'S DUE TO A NEW VIRUS, NEW KNOWLEDGE OR THE EXISTENCE OF HEALTH DISPARITIES. INDEED HEALTH DISPARITIES PRESENT UNIQUE INCLUSION CHALLENGES AND UNDERSCORE THE NEED TO THINK CREATIVELY ABOUT RECRUITMENT AND RETENTION. IT MEANS ACHIEVING RACIAL AND ETHNIC DIVERSITY--EXCUSE ME--AMONG PARTICIPANTS THROUGH LONG-TERM COMMUNITY FOCUSED EFFORTS. IT INCLUDES DIVERSITY AMONG RESEARCHERS, RELATIONSHIP BUILDING WITH STAKEHOLDERS, LINGUISTICALLY, CULTURALLY COMPETENT STAFF NUMBERS AND OTHER TRUST-BUILDING ACTIVITIES. IN MEANS EMPLOYING INNOVATIVE STUDY DESIGNS SO WE CAN LEARN MORE FROM STUDIES. THESE INCLUDE PRAGMATIC TRIALS, ADAPTIVE DESIGNS AND EVEN SEX STRATIFIED RANDOMIZATION. IT MEANS COLLABORATE WITH THE FDA TO SUPPORT INCLUSION OF DIVERSE WOMEN IN CLINICAL TRIALS. FINALLY IT MEANS DEVELOPING RESOURCES FOR RESEARCHERS, TOWARD THAT END, ORWH IN COLLABORATION WITH OTHER NIH PARTNERS RECENTLY UPDATED THE NIH INCLUSION OUTREACH TOOL KIT. LET ME CONCLUDE BY EMPHASIZING THE IMPORTANCE OF KEEPING INCLUSION OF WOMEN OF ALL AGES AND THE STUDY OF SEX AND GENDER INFLUENCES, FRONT AND CENTER. THERE IS SO MUCH WE DO NOT KNOW. YOU COULD SAY WE COULD BE MISSING AT LEAST HALF OF THE STORY, SO IF WE DON'T UNDERSTAND WHERE, WHEN, WHY, AND HOW SEX IS INFLUENCING HUMAN HEALTH AND DISEASE, WE DON'T KNOW WHAT TO DO ABOUT IT. IT'S MY PLEASURE TO BE HERE TODAY AND I'M LOOKING FORWARD TO TODAY'S WORKSHOP. THANK YOU. >> GOOD MORNING, I'M ELISEO PEREZ-STABLE DIRECTOR NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES AND I'M DELIGHTED TO PRESENT FROM MY HOME IN THE DISTRICT OF COLUMBIA. ON BEHALF OF OUR INSTITUTE, I WANT TO WELCOME ALL PARTICIPANTS AND THANK THE ORGANIZERS ESPECIALLY AND ALL THE PRESENTERS FOR THIS IMPORTANT EVENT. AT NIMHD, WE FOCUS ON THE HEALTH OF RACIAL AND ETHNIC MINORITIES AND POOR PEOPLE FROM ALL COMMUNITIES AND OTHERS IMPACTED BY HEALTH DISPARITIES. NIMD SCIENCE HOLDS THE SOCIAL DETERMINANTS OF HEALTH AS FUNDAMENTAL FACTORS CONTRIBUTING TO OUTCOMES. ABOVE ALL, THE SOCIAL CONSTRUCT OF RACE AND ETHNICITY IN ASCERTAINMENT OF SOCIOECONOMIC STATUS ARE FUNDAMENTAL TO ALL HUMAN RERESEARCH AND ESSENTIAL TO MEASURE ACCURATELY. PLUS, IN CONSIDERING INCLUSION ACROSS THE LIFE SPAN, WE ENCOURAGE ALL SCIENTISTS TO FACTOR THESE VARIABLES IN ADDITION TO AGE AND GENDER. THE MOST IMPORTANT PART OF ANY CLINICAL RESEARCH ENDEAVOR IS THE INCLUSION OF ALL POPULATION GROUPS ACROSS THE LIFESPAN WHO WILL BE IMPACTED BY THE RESEARCH. TODAY HALF OF ALL CHILDREN IN THE UNITED STATES IDENTIFY AS A RACIAL AND ETHNIC MINORITY GROUP. INCLUSION OF DIVERSE PARTICIPANTS MAKES COMMON SENSE, IS AN IMPERATIVE MANDATE IN SOCIAL JUSTICE GOALS AND IS A CRITICAL CONTRIBUTOR TO OUTSTANDING SCIENCE. THERE ARE DISCOVERIES IN IDENTIFYING MECHANISTIC PATHWAYS AND UNDERSTANDING HOW IMPLEMENTATION OF WELL CONTROLLED INTERVENTIONS ARE EFFECTIVE IN COMMUNITIES THAT WILL BE LEFT ON THE TABLE IF INCLUSION IS NOT CENTRAL TO CLINICAL RESEARCH FROM THE START. TO BRING IN TO A REALITY CHECK-POINT, HOW CAN WE PERSUADE AFRICAN AMERICANS AND LATINOS AND LATINAS FOR CASES OF COVID-19 NATIONAL ARE IN THESE 2 POPULATION GROUPS. INCLUSION EFFORTS MAY TAKE MORE RESOURCES AND DIFFERENT SKILLS TO RECRUIT PEOPLE OF COLOR, WHO ARE OFTEN UNDERSERVED AND FREQUENTLY HARBOR MISTRUST OF INSTITUTIONS, SYSTEMS AND GOVERNMENT BASED ON THE LEGACY OF STRUCTURAL RACISM AND DISCRIMINATION. IT TAKES MORE FACE TIME, DIRECT PERSONAL MESSAGES, CIVIC RESOURCES AND COMMUNITY ENGAGEMENT AND INVESTMENT FROM THE SCIENTISTS AND THE ENTIRE RESEARCH TEAM TO FACILITATE AND PROMOTE PARTICIPATION. HAVING INVESTIGATORS WHO REFLECT THE STUDY POPULATION IS OFTEN EFFECTIVE GIVEN THEIR UNDERSTANDING OF CULTURAL NEEDS AND NUANCES AND TRUSTED PRESENCE BY THE MINORITY STUDIED POPULATION. GIVEN OUR CURRENT SOCIETAL CHALLENGES, WE CAN EXPECT TO SEE THE IMPACT ON HEALTH OUTCOMES FOR YEARS TO COME. EXPANDING LIFE COURSE RESEARCH AND THE INCLUSION OF MINORITIES IN CLINICAL RESEARCH WILL CONTINUE TO BE IMPERATIVE TOWARDS OUR EFFORTS TO IMPROVE PUBLIC HEALTH. THANK YOU FOR YOUR PARTICIPATION IN THIS WORKSHOP AND I LOOK FORWARD TO THE PRESENTATIONS. >> WE WILL NOW HAVE PRESENTATIONS ON IMPLEMENTATION OF THE IALL POLICY, OUR PRESENTERS WILL BE NONI BYRNES, DISTRICTOR FOR THE CENTER FOR SCIENTIFIC REVIEW AND PATRICIA BRENNAN, DIRECTOR IT NATIONAL LIBRARY OF MEDICINE. WE WOULD LIKE TO ENCOURAGE OUR VIEWERS TO USE THE CHAT FUNCTION AND SUBMIT QUESTIONS AND COMMENTS. THANK YOU. >> THANK YOU. I WANT TO THANK THE ORGANIZERS AND ESPECIALLY MY COLLEAGUE MARIE BERNARD FOR ALLOWING ME THIS OPPORTUNITY TO COME AND TALK TO ALL OF YOU ABOUT THE IMPLEMENTATION OF THIS POLICY, I'M NONI BYRNES, I'M THE DIRECTOR FOR THE CENTER FOR SCIENTIFIC REVIEW. NEXT SLIDE. OKAY, I WILL BE TALKING ABOUT IMPLEMENTATION IN THE PEER REVIEW PROCESS AND WE'VE GONE THROUGH THIS FOR ABOUT A YEAR NOW. POLICY IS ABOUT 1 YEAR OLD AND WE HAVE A FEW UPDATES BUT LET ME SORT OF START WITH A LITTLE BIT OF BACKGROUND. NEXT SLIDE. SO YOU'VE HEARD SOME OF THIS FROM MY COLLEAGUES EARLIER BUT THE BACKGROUND OF THE POLICY CHANGE WAS LARGELY WHAT WE WERE SEEING IN TERMS OF THE PARTICIPANTS IN THEA APPLICATIONS THAT WERE BEING RECEIVED IN HUMAN SUBJECTS RESEARCH TO THE NIH. SO THERE WERE ARBITRARY AGE LIMITS FOR ENROLLMENT, OFTEN THAT WAS NOT BASED ON SCIENTIFIC PRINCIPLES BUT MUCH MORE ON EASE OF RECRUITMENT OR STUDY DESIGN. THERE WAS AN ISSUE OF EXCLUSION CRITERIA AND JANINE, MENTIONED THAT EARLIER USING EXCLUSION CRITERIA THAT ARE SOMEWHAT ARBITRARY AND MIGHT EXCLUDE OLDER PEOPLE SUCH AS CO MORBIDITY. AND WHAT WE SAW THAT WAS SUBJECTS ON EITHER END OF THE AGE RANGE WERE NOT BEING RECRUITED EVEN THOUGH THOSE ARE THE VERY POPULATIONS AND THAT'S ESPECIALLY CLEAR NOW WITH THE PANDEMIC THAT WE'RE GOING THROUGH RIGHT NOW AND THOSE ARE THE POPULATIONS AND THE GREATEST NEED OF CLINICAL INTERVENTIONS. WHAT THAT RESULTED IN IS A GAP IN THE EVIDENCE BASE, SO YOU DON'T HAVE INTERVENTION OR CLINICAL GUIDE LINES THAT ARE SUBSTANTIVE FOR OLDER ADULTS AND FOR CHILDREN. AND THEN FROM THE RESEARCH PERSPECTIVE THERE WAS THE LACK OF ADEQUATE INFORMATION, DISAGGREGATED INFORMATION TO BE ABLE TO UNDERSTAND DIFFERENTIAL OUTCOMES ACROSS DIFFERENT AGES. NEXT SLIDE. OKAY, SO IN DECEMBER 2017, THE NIH ISSUED A REVISION NOTICE OF POLICY AND YOU--AT THE END OF MY TALK, I HAVE A SLIDE ON ALL OF THE RESOURCES SO PEOPLE CAN GO AND LOOK AT THE LINKS CORRECTLY AND READ IN DETAIL BUT THE MAIN CHANGE HERE WAS EXPANDING THE SCOPE OF THE AGE RANGE TO INCLUDE OLDER ADULTS NEXT SLIDE. SO THE POLICY NOTICE 18-116 MANDATES THAT PARTICIPATES OF ALL AGES SHOULD BE INCLUDED IN NIH RESEARCH INVOLVING HUMAN SUBJECTS UNLESS THERE IS A SCIENTIFIC OR ETHICA REASON FOR EXCLUDING THEM. AS MENTIONED BEFORE, THIS WAS EFFECTIVE FOR ALL COMPETING NIH APPLICATIONS THAT WERE SUBMITTED ON OR AFTER JANUARY 2019. NEXT SLIDE. AND SO IN ADDITION TO BROADENING THE APPLICABILITY OF THE POLICY, THE POLICY ALSO CLARIFIED APPLICABILITY JUST BEYOND--THAT ARE ACCEPTABLE FOR EXCLUSION BASED ON AGE. AND IT INCLUDES SOME REPORTING REQUIREMENTS AND MY COLLEAGUE PATTY BRENNAN WILL BE TALKING MORE ABOUT THAT. NEXT SLIDE. SO I WILL GET MORE INTO HOW THIS IS GOING AND HOW WE'RE IMPLEMENTING THIS IN PEER REVIEW WHENEVER THERE'S A NEW POLICY IN PEER REVIEW, IT TAKES A LITTLE WHILE FOR IT TO CATCH ON. WE HAVE JUST A CSR ALONE THAT WE USE 18,000 REVIEWERS AND 1600 MEETINGS A YEAR AND YOU CAN IMAGINE THAT A POLICY CHANGE YOU KNOW TAKES A LITTLE WHILE TO TAKE, BUT I THINK FROM THE PERSPECT PERSPECTIVE OF THE SCOPE OF THIS POLICY IT'S GOING PRETTY WELL AS MARIE MENTIONED. SO STARTING WITH THE SUMMER OF 2019 REVIEW MEETINGS WHICH WAS THE FIRST SET OF APPLICATIONS THAT CAME IN AFTER JANUARY 2019, IN IH REVIEWERS--NIH REVIEWERS HAD INSTRUCTIONS TO EVALUATE WHETHER THE AGE RANGE OF THE SUBJECTS MADE SENSE BASED ON THE PROPOSED QUESTIONS AND THEY WERE ASKED TO RATE THE INCLUSION PLANS FROM THE APPLIC ANTS AS EITHER ACCEPTABLE OR UNACCEPTABLE. NEXT SLIDE. SO TO GIVE YOU A LITTLE CONTEXT, THE NIH USES 5 SCORED REVIEW CRITERIA, SIGNIFICANCE, INVESTIGATORS, INNOVATION, APPROACH AND ENVIRONMENT. IN ADDITION, THERE ARE ADDITIONAL REVIEW CRITERIA, THE PROTECTION OF HUMAN SUBJECTS INCLUSION PLANS WHICH NOW WILL INCLUDE, DOES INCLUDE THE LIFE SPAN POLICY. MANAGEMENT OF BIOHAZARDS AND INVERTEBRATE ANIMALS AND ALL OF THESE WAY INTO THE IMPACT SCORE WHICH IS THE FINAL SCORE FOR EVERY APPLICATION. NEXT SLIDE. PREVIOUS SLIDE. SO WHERE--WHERE THIS COMES INTO PLAY IS IN THE APPROACH SECTION, THE INCLUSION PLANS AND OVERALL IMPACT SCORE, THIS IS WHERE THIS POLICY BECOMES RELEVANT. NEXT SLIDE. SO WHEN YOU THINK ABOUT THE APPROACH, REVIEWERS ARE ASKED TO EVALUATE THE RIGOR OF THE EXPERIMENTAL DESIGN AND LEAVING OUT IN AN ARBITRARY MANNER OLDER ADULTS FROM THE DESIGN WILL IMPACT THE EVALUATION OF THE APPROACH. EVERY APPLICANT ALSO SUBMITS A SPECIFIC INCLUSION PLAN WITH THEIR APPLICATION AND THAT'S EVALUATED AS WELL UNDER ADDITIONAL REVIEW CRITERIA, AND THEN OF COURSE THE OVERALL IMPACT SCORE, THERE ARE MANY AREAS IN THE APPLICATION THAT INFLUENCE THAT BUT IF THE STUDY POPULATION IS NOT REPRESENTATIVE OF THE POPULATION, THAT SHOULD IMPACT THE OVERALL IMPACT SCORE AND FOR UNACCEPTABLE INCLUSION PLANS THERE SHOULD BE--YOU KNOW WE'VE ASKED REVIEWERS TO CONSIDER THAT IN ASSIGNING OVERALL IMPACT SCORE. NEXT. OKAY, AND SO THE PROCESS WORKS IN THAT INDIVIDUAL REVIEWERS INDEPENDENTLY ASSESS THE LIFE SPAN POLICY IN THEIR CRITIQUES AND THIS IS JUST SNAPSHOTS OF THE CRITIQUE TEMPLATES THE REVIEWERS HAVE, JUST GO AHEAD AND PULL UP THE REST. NEXT. AND NEXT. OKAY. SO THESE ARE THE CRITIQUE TEMPLATES, YOU CAN SEE IN THE APPROACH SECTION, THEY CAN NOTE THE STRENGTHS AND WEAKNESSES BASED ON THE RIGOR, THE OVERALL I AM NOT PACT SECTION OF COURSE, THEY CAN MENTION THAT BUT FOR THE INCLUSION ACROSS THE LIFE SPAN, THERE'S A MODIFIED CRITIQUE TEMPLATE THAT ALLOWS A DROP DOWN MENU FOR REVIEWERS TO INDICATE WHETHER THE AGE RANGE HAS BEEN JUSTIFIED SCIENTIFICALLY OR NOT. NEXT. AND THEN DURING THE DISCUSSION, THE PANEL, REVIEWERS COME TOGETHER AS A WHOLE AND THEY DISCUSS A SUBSET OF THE APPLICATIONS, THE HIGHEST RANKING APPLICATIONS AND THERE ALSO THE PANEL AS A WHOLE DISCUSSES THE COMPLIANCE WITH THE POLICY OR WHETHER IT'S JUSTIFIED OR NOT, AND THIS IS DONE BEFORE FINAL SCORING BECAUSE IT IS SUPPOSED TO IMPACT THE FINAL SCORE. SO THE ENTIRE PANEL AS A WHOLE ASSESSES THAT. NEXT. SO, YOU KNOW AGAIN AS THE EVALUATION PROCESS, I WANTED TO GIVE KIND OF A NAP SHOT OF WHERE EXACTLY WE'RE TARGETING REVIEWER TRAINING AND WHAT OCCURS IN THE PROCESS SO IN THE PREMEETING TIMES, SCIENTIFIC REVIEW OFFICERS ARE TRAINING, REVIEWERS AND CHAIRS, ANYTIME THERE'S A NEW POLICY, THERE'S MORE EMPHASIS ON TRAINING REVIEWERS PRIOR TO THE MEETING BEFORE THEY EVEN RECEIVE APPLICATIONS, THEN AGAIN AFTER THEY RECEIVE APPLICATIONS. THE CRITIQUE TEMPLATES AS I MENTIONED BEFORE INCLUDE THE EVALUATION AND DROP DOWN MENUS AND THEN WE'VE ASKED SROs AND SROs ARE EXAMINING REVIEWER CRITIQUES AND AGAIN WE DO THIS FOR MOST NEW POLICIES TO MAKE SURE THAT THE REVIEWERS ARE UNDERSTANDING AND IMPLEMENTING THIS IN THEIR EVALUATION. SO THE SROs EXAMINE THE CRITIQUES BEFORE THE MEETING TO SEE THAT THE INCLUSION PLANS ARE ADDRESSED. THEN DURING THE MEETING, THE CHAIR PERSON AND THE SRO INSURE THAT THIS IS SPECIFICALLY DISCUSSED BEFORE THE FINAL SCORE IS ASSIGNED TO AN APPLICATION. AFTER THE MEETING, APPLICATIONS ARE FLAGGED, ACCEPTABLE OR UNACCEPTABLE WITH RESPECT TO THIS POLICY AND A NOTE IS INCLUDED IN THE SUMMARY STATEMENT IF IT'S UNACCEPTABLE. NEXT. SO, NEXT. SO THE REVIEWER WORK SHEET, THAT WE HAVE PROVIDED TO REVIEWERS OVER THE LAST YEAR TO ASSESS THE POLICY IS 2 PARTS. ONE IS, YOU KNOW IS THERE A PLAN AVAILABLE? IS THERE A PLAN AND IS THERE A DESCRIPTION? AND IF THERE'S NO DESCRIPTION OF INCLUDING, YOU KNOW OF INCLUDING ACROSS THE LIFE SPAN, THEN THE INCLUSION PLANS MUST BE RATED UNACCEPTABLE AND THAT'S WHAT WE ASKED REVIEWERS TO DO. NEXT. IF WELL IS A DESCRIPTION THEN WE ASK THEM TO LOOK AT THE JUSTIFICATION, WHETHER IT MAKES SENSE SCIENTIFICALLY, IS IT SCIENTIFICALLY AND ETHICALLY APPROPRIATE? AND LOOKING AT THE POINTS IN SECTION 3 AND I WILL WALK YOU THROUGH A LITTLE BIT OF THE CRITERIA THAT ARE ALLOWED FOR EXCLUSION AND NOT ALLOWED AND THAT'S WHAT THEY SEE IN SECTION 3. AND AGAIN, THEY ASSESS THE APPROPRIATENESS OF THE STUDY GROUP WITH RESPECT TO AGE AND THEN THEY RATE THE INCLUSION PLANS AS EITHER UNACCEPTABLE OR ACCEPTABLE. NEXT. AND THEN EACH REVIEWER IS ASKED THAT IF THEY'RE RATING THE PLAN UNACCEPTABLE EITHER BECAUSE THERE IS NO ADEQUATE DESCRIPTION OR THAT THE JUSTIFICATION IS INADEQUATE, THEY'RE SUPPOSED TO INCLUDE SPECIFIC COMMENTS IN THE CRITIQUE THAT MARIE REFERRED TO AND WE'RE STILL EXAMINING HOW WELL THAT'S GOING. NEXT. SO ACCEPTABLE EXCLUSIONS, AGAIN EITHER SCIENTIFIC OR ETHICAL AND WHAT DO THOSE LOOK LIKE AND THIS IS THE INSTRUCTIONS WE GIVE TO REVIEWERS, NEXT. SO SCIENTIFIC, THE POLICY IS PRETTY CLEAR ON THIS, THERE ARE CERTAIN REASONS THAT ARE SCIENTIFICALLY OKAY FOR EXCLUDING AGE RANGES. ONE IS THRA YOU KNOW YOU HEARD THIS BEFORE, THE CONDITION IS NOT RELEVANT TO THE EXCLUDED GROUP, YOU KNOW AGAIN, ALZHEIMER'S AND CHILDREN, WE DON'T NECESSARILY NEED TO HAVE CHILDREN IN A STUDY RELATED TO ALZHEIMERS. THE KNOWLEDGE MIGHT ALREADY EXIST EXIST IN THE EXCLUDED GROUP SO THERE MIGHT BE A DRUG THAT'S APPROVED IN ADULTS AND NOW A STUDY IS BEING DESIGNED TO LOOK AT ITS EFFECT IN CHILDREN, SO YOU COULD EXCLUDE IN ESSENCE ADULTS. A SEPARATE STUDY--THIS THIRD BULLET IS VERY MUCH ABOUT THE GOALS OF THE SCIENTIFIC PROJECT. IF THE GOALS OF THE PROJECTS ARE VERY TARGETED, YOU KNOW YOU ARE LOOKING AT OUTCOMES IN ADOLESCENT, YOU KNOW USE OF OPIOID IN ADOLESCENT, IT IS REASONABLE TO INCLUDE ADOLESCENCE ALONE IN THAT AGE GROUP. AND THEN THE FINAL 1 IS MORE ABOUT LONGITUDINAL STUDIES, THINGS THAT HAVE ALREADY BEGUN, HAVE AN ONGOING, PREENROLLED PARTICIPANTS AND YOU CAN'T GET AGE INCLUSIVE DATA BUT THIS IS SORT OF THE EXTENT OF EXCLUSION. NEXT. ETHICAL IS IF THERE ARE LAWS OR REGULATIONS THAT BAR CERTAIN AGE GROUPS FROM BEING INCLUDED. AGAIN, THE BAR FOR CHILDREN IS--VERSUS CONSENTING ADULTS CAN DIFFER, AND THAT'S OKAY. IF THERE'S AN UNACCEPTABLE RISK TO THE EXCLUDED GROUP, IF AN IRB WOULD FIND IT TO BE UNACCEPTABLY RISKY THEN THAT IS OKAY TO EXCLUDE. NEXT. SO THE REASONS THAT ARE NOT OKAY FOR EXCLUSION, 1 IS COST, THAT'S NOT AN ACCEPTABLE REASON. CONVENIENCE, YOU KNOW THE AVAILABILITY OF A POPULATION. CONCERNS ABOUTINIZE AND --NOISE AND DATA AND I WILL SHOW YOU EXAMPLES WHERE THIS COMES UP AND THEN ANY OTHER REASON REALLY THAT ALIGN WITH THE SCIENTIFIC GOALS OF THAT PROJECT OR ETHICAL CONCERNS. INTERESTINGLY WHAT WE'VE SEEN THUS FAR IN THIS FIRST YEAR IS THAT THE MOST COMMON REASON IS ACTUALLY JUST THE LACK OF ANY EXPLANATION FOR THE AGE GROUP CHOSEN. AND I THINK THAT HAPPENS WHENEVER WE IMPLEMENT A NEW POLICY, ITIC TAKEN--THEYS A WHILE FOR THE COMMUNITY TO UNDERSTAND WHAT'S REQUIRED AND FOR EVERYONE TO GET ON BOARD BUT IT'S GETTING THERE. NEXT. NOT INCLUDING THEM IS UNACCEPTABLE AND THE OTHER 2 ARE ABOUT EXCEPTIONS OR ADDEDDAING NOISE TO THE DATA, SO GENERATIONAL DIFFERENCES IN THE USE OF TECHNOLOGY FOR OLDER ADULTS AND YOUNGER CHILDREN SO THEY DON'T WANT TO ADD NOISE AND BIAS THE DATA. WELL, YOU'RE NOT ACTUALLY GETTING GOOD OUTCOMES OR MEANINGFUL INFORMATION FROM THAT STUDY IF YOU DON'T INCLUDE A REPRESENTATIVE AGE GROUP AND THE LAST 1, THE EXAMPLE OF LIMITING HORMONAL VARIATION BECAUSE THINGS EVIDENCE THAT AGING RESULTS AND CHANGES TO THE BRAIN SIZE SO THEY'RE GOING TO EXCLUDE PEOPLE OVER THE AGE OF 50. SO THIS WOULD ALL BE UNACCEPTABLE EXCLUSIONS AND WE GIVE EXAMPLES TO OUR REVIEWERS AS TO HOW TO TACKLE THOSE. NEXT. SO WHAT ARE OBSERVATIONS? AS I MENTIONED BEFORE, IT'S ONLY BEEN ABOUT A YEAR. NEXT. AND OVER THE LAST YEAR, WHICH IS,A ROUND 4 ROUNDS, COUNCIL ROUNDS OF DATA, WE HAVE REVIEWED NIH OVER ALL HAS REVIEWED JUST OVER 46,000 APPLICATIONS INVOLVING HUMAN SUBJECTS RESEARCH AND ABOUT 3 PERCENT OF THEM HAVE BEEN RATED UNACCEPTABLE DUE TO THIS POLICY, SO THE POLICY IS BEING APPLIED AND ASSESSED. NEXT. AND THE REST, YOU KNOW BECAUSE THE--WE'RE STILL SORT OF IN THE EARLY STAGES WE'RE EXAMINING CRITIQUES, WE ARE TALK TO OUR SCIENTIFIC REVIEW OFFICERS AND REVIEWERS, THE GENERAL OBSERVATIONS THAT WE HAVE ARE THAT THE REVIEWERS ARE COMMENTING ON INCLUSION ACROSS THE LIFE SPAN, BOTH IN CRITIQUES AND DURING THE MEETING ITSELF. HEY SEEM TO BE DISTINGUISHING OKAY BETWEEN ACCEPTABLE AND UNACCEPTABLE RATINGS IN REGARD TO THE IL POLICY AND INTERESTINGLY MOST APPLICATIONS THAT ARE MARKED UNACCEPTABLE FOR INCLUSION ALSO GET WEAKER SCORES SO IT DOES APPEAR THAT THE INCLUSION PLAN ASSESSMENT DOES SEEM TO BE AFFECTING SCORE. NEXT. SO WHAT HAPPENS TO APPLICATIONS THAT COME OUT OF PEER REVIEW œCOMPLIANCE TO THE PLAN IN WELL IF IT'S NOT SCORED AND NOT DISCUSSED THE APPLICANT GETS BACK THE RAW CRITIQUES FROM THE INDIVIDUAL REVIEWERRERS WITH THEIR CONCERNS NOTED. IF IT IS DISCUSSED AND IS SCORED THEN THE SUMMARY STATEMENT IS FLAGGED UNACCEPT AND A NOTE IS INCLUDED AND IT'S ALSO CODED UNACCEPTABLE IN THE NIH SYSTEM SO THAT THE SUBSEQUENT PARTS OF NIH THAT DEAL WITH THE PROGRAM AND GRANTS MANAGEMENT HAVE ACCESS TO THAT. THE MOST IMPORTANT POINT HERE IS THAT ANY APPLICATION THAT'S GIVEN AN UNACCEPTABLE CODE, YOU WILL RESULT IN A BAR TO FUNDING THAT MUST BE RESOLVED BEFORE THAT APPLICATION IS FUNDED. AND IT DOESN'T MATTER IF IT'S GOT A PERFECT SCORE OR 1 PERCENTILE, SO THAT HAS TO BE RESOLVED. NEXT. THESE ARE ALL THE RESOURCES, THE FIRST IS JUST THE INCLUSION POLICY, CAN YOU LOOK AT THE DETAILS THERE, FAQs AND THE FINAL STAGE AND THEN THE GUIDANCE FOR PEER REVIEWERS THAT INCLUDES THE CHECK LIST AS I MENTIONED WAS THERE. NEXT. AND I'M HAPPY TO ENTERTAIN QUESTIONS. >> ACTUALLY--THIS IS PATTY, I'M GOING TO BE SPEAK NOTHING A FEW MINUES ABOUT HOW 1 DOCUMENT AND COMPLIANCE WHEN 1 IS DEALING WITH AN APPLICABLE CLINICAL TRIAL BUT LAWN MOWER IS THE MONITORING SCHEME FOR OTHER PROJECTS THAT ARE NOT SPECIFICALLY CLINICAL TRIALS, FOR EXAMPLE, OBSERVATIONAL STUDIES? IS IT THE RPPR OR SOME OTHER WAY? YOU'RE ON MUTE NONI. >> OKAY. SO THIS IS POST PEER REVIEW WHICH IS WHY I'M A LITTLE LESS CLEAR ON WHAT HAPPENS, POST PEER REVIEW BUT I DO THINK THAT IT HAPPENS AND IN THE PROGRESS REPORTS THERE'S--HANG ON LET ME JUST TAKE A LOOK. YES. RIGHT. SO THE NIH IS SUPPOSED TO COLLECT AND ANNUALLY REPORT INFORMATION IN PROGRESS REPORTS AND THERE'S A DECISION AREA. I THINK THE FAQs REALLY OFFER A GOOD MAP FOR WHAT OCCURS POST REVIEW. OKAY, NO AND I WAS GOING TO SAY TO PATTY, SHE PROBABLY ALREADY KNOWS THAT FOR CLINICAL TRIALS, THE REPORTING HAS TO BE DISAGGREGATED AND REPORTED ON THE INDIVIDUAL LEVEL. YEAH, SORRY, MARIE, GO AHEAD. >> SO FROM THE CHAT BOX THERE'S A QUESTION ABOUT WHAT SCIENTISTS, WHAT ARE THE OPTION SAYS FOR SCIENTISTS IF THEY DISAGREE WITH THE ASSESSMENT IN TERMS OF THE ADEQUACY OF ADDRESSING THE IALL ISSUES? >> RIGHT. SO WHAT I THINK HAPPENS POST REVIEW IS WHEN THERE IS A FLAG UNACCEPTABLE, WHAT I HAD MENTIONED IS THAT IT HAS TO BE RESOLVED AND THE RESOLUTION OCCURS USING INTERACTIONS WITH THE PROGRAM STAFF AND YOU MAY BE ABLE TO ACTUALLY ANSWER THAT EVEN BETTER MARIE, THAT PROGRAM STAFF HAVE TO WORK WITH THE APPLICANT TO ATTAIN RESOLUTION AND I ASSUME AT THAT POINT IS WHERE DISAGREEMENTS AND A DIFFERENT PERSPECTIVE MIGHT BE CONSIDERED. BUT THERE IS NO--IT'S A BAR TO FUNDING UNTIL THERE IS AN ADEQUATE RESOLUTION, THAT'S BEYOND REVIEW. >> THANK YOU, YES. COMING FROM THE AGING INSTITUTE IT'S USUALLY NOT AN ISSUE, NOT ADEQUATELY, MEANING OLDER ADULTS, IT'S THE QUESTION WHY ARE YOU EXCLUDING YOUNGER ADULTS. >> RIGHT. OKAY. ANYTHING ELSE? ALL RIGHT. THANK YOU. >> SO JOAN WILL YOU BE INTRODUCING ME OR DO YOU INTRODUCE YOURSELF. >> SORRY, WE WILL NOW HAVE A PRESENTATION BY DR. PATRICIA BRENNAN DIRECTOR NATIONAL LIBRARY OF MEDICINE. >> THANK YOU VERY MUCH. THANK YOU AS A START UP. NEXT SLIDE, PLEASE. TODAY I'M GOING TO BE SPEAKING TO YOU SPECIFICALLY ABOUT HOW THE NATIONAL LIBRARY OF THE MEDICINE IS FOSTERING INCLUSION ACROSS THE LIFE SPAN AND NIH FUNDED RESEARCH AND SPECIFICALLY OUR RESPONSIBILITIES ARE TO SUPPORT ACCELERATED ENROLLMENT AND RESPONSIBLE REPORTING, NEXT SLIDE, PLEASE, I'M GOING TO BE TALKING ABOUT 4 KEY AREAS, NEXT SLIDE, THERE WE ARE. ELEMENTS AS AN INTRODUCTION TO CLINICALTRIALS.GOV AND THEN I WILL BE TALKING ABOUT REPORTING BY AGE, DEMONSTRATING THE IMPACT AND SPECIAL CONSIDERATIONS. THE NEXT SLIDE, PLEASE. I'D LIKE YOU TO BEGIN WITH ME, THOUGH AT THE PATIENT EXPERIENCEOT FAR LEFT SIDE OF THE SLIDE. IF YOU FOLLOW THE BLUE ARROW, THE TRAJECTORY UP, PATIENT PHENOMENON IS RECORDED AND CODIFIED NOW IN TERMINOLOGIES AND WE'RE INCREASINGLY USING NEW LANGUAGES SUCH AS SNOMED, LOIRKS INC FOR LABORATORY AND OTHER OBSERVATIONS. REEBTLY THE OFFICE OF THE NATIONAL COORDINATOR OF HEALTH IT INDICATED A CORE SET FOR INTEROPERABILITY, THE U.S. CORE INTEROPERABILITY DATA SAID USCDI IS ESTABLISHED AS A WAY OF IDENTIFYING 27 PARAMETERS THAT MUST BE PRESENT IN ALL CLINICAL RECORDS INCLUDING SUCH THINGS AS ALLERGIES, OBSERVATIONS IN CLINICAL NOTES AS WELL AS PATIENT DEMOGRAPHICS. THERE'S RECENTLY ALSO BEEN WORK DONE NATIONALLY AND SUPPORTED AT THE NIH FROM POLICY ON SOMETHING REFERRED TO AS THE FIRE STANDARD. FHIR, THAT'S FAST HEALTHCARE INTEROPERABILITY RESOURCE. THE FHIR IS A WAY OF CODIFYING MESSAGES AND MAKING THEM ACCESSIBLE IN AN ELECTRONIC EXCHANGE. THINK ABOUT THE FHIR STANDARD MUCH THE SAME WAY AS YOU THINK ABOUT THE FRONT OF AN ENVELOPE THAT YOU'RE ADDRESSING TO A RECIPIENT. THE NAME OF THE RECIPIENT GOESOT FIRST LINE, THE STREET NUMBER AND NAME GOES ON THE SECOND LINE, THE CITY AND STATE AND ZIP CODE ON THE THIRD LINE, THAT'S A STRUCTURAL STANDARD. SO IN ORDER TO EXTRACT INFORMATION FROM THE CLINICAL EXPERIENCE, EVEN IF WE HAVE FORMAL TERMINOLOGIES AND IT'S ORGANIZED INTO THIS CORE DATA SET FOR INTERROPERABILITY, IT STILL HAS TO BE PROCESSIBLE IN A WAY THAT CAN BE COMPUTER UNDERSTOOD AND THATIA WHERE THE FHIR STANDARD COMES IN. NOW OUR INTEREST TODAY IS TO GET THAT DATA INTO THE RESEARCH RECORD BUT GENERALLY THAT DATA ALSO IS--ONCE IT'S PROCESSED IN A FHIR STANDARD IT IS MUCH EASIER TO INTER OPERATE TO EXCHANGE WITH OTHER CARE FACILITIES SUCH AS FROM A NURSING HOME TO A HOSPITAL OR FROM A CLINIC TO AN IN-PATIENT AREA. NOW LOOK ACROSS THE BOTTOM LINE FOR A MOMENT. THERE'S GREAT INTEREST AT THE NIH WHEN SOMETHING REFERRED TO AS COMMON DATA ELEMENTS. THESE ARE SYSTEMATIC WAYS TO LABEL PHENOMENON OF INTEREST IN A PARTICULAR RESEARCH PROJECT, MANY GROUPS DEVELOP COMMON DATA ELEMENTS. AND ELEMENTS WE USE TO DESCRIBE A PERSON TO DESCRIBE A PERSON HAVING ALZHEIMER'S DISEASE. WHAT COMMON DATA ELEMENTS SIMPLY MEAN IS THAT A SERIES OF SUBJECT MATTER EXPERTS HAVE COME TOGETHER TO SAY IF WE'RE INTERESTED IN A SPECIFIC PHENOMENON, WE WOULD LIKE IT TO BE MEASURE ED IN A PARTICULAR WAY. NEXT SLIDE, PLEASE. HERE'S AN EXAMPLE OF SOME OF THE COMMON DATA ELEMENTS THAT WE'RE WORKING ON THAT WE REFER TO AS THE MINIMUM OR ESSENTIA WILL COMMON DATA ELEMENTS FOR ANY PERSON INVOLVED IN A COVID STUDY. ON THE LEFT-HAND SIDE YOU SEE PERSON FOCUSED AND THERE'S A COLUMN AND OF INTEREST IN THIS GROUP IS THE THIRD ITEM DOWN, AGE. IN THE CENTER YOU SEE INFECTIOUS DISEASE TESTING TO OUTCOMES AND YOU SEE A NUMBER OF DIFFERENT COMMON DATA ELEMENTS, MORBIDITYS FOR EXAMPLE, DIAGNOSIS OR PSYCHOSOCIAL IMPACT, THE NEXT SLIDE, PLEASE. COMMON DATA ELEMENTS ESSENTIALLY ARE A QUESTION AND ANSWER PAIR, A COMBINATION OF A DEFINABLE ANSWER PAIRED WITH THE SPECIFIED SET OF SIMILARLY CODED PERMISSIBLE RESPONSES TO THAT QUESTION. NOW IN THE CASE OF THIS GROUP TODAY, WE'RE INTERESTED IN ONLY 1 QUESTION AND THAT IS AGE. THESE COMMON DATA ELEMENTS THOUGH EXTEND BEYOND DATA GRAPHICS AND THEY'RE CORE OR COMMON TO MULTIPLE DATA SETS IN DIFFERENT STUDIES AND CAN BE STRUCTURED AS A SINGLE DATA ELEMENT WHICH IS OFTEN THE AGE IS, BUT COULD BE A COLLECTION OF DATA ELEMENTS SUCH AS--[AUDIO CUTS OUT ], CEEs TYPICALLY REPRESENT CORE THAT IS ESSENTIAL OR COMMON VARIABLES, NOT ALL VARABLES. NEXT SLIDE, PLEASE AND TODAY'S CONVERSATION IS REALLY FOCUSING ON THE USE OF COMMON DATA ELEMENTS FOR AGE AND SPECIFICALLY IN APPLICABLE CLINICAL TRIALS. BECAUSE WHAT I'VE BEEN ASKED TO ADDRESS FOR YOU IS HOW THE NIH'S REPOSITORY, CLINICALTRIALS.GOV, SERVES TO ACQUIRE INFORMATION ABOUT AGE ACROSS THE LIFE SPAN AND HOW WE ACTUALLY ENCODE THAT AND USE THAT IN OUR CLINICALTRIALS.GOV OPERATION. NEXT SLIDE, PLEASE. SO I WANT YOU TO THINK ABOUT THE DIFFERENT WAYS THAT WE CAN THINK ABOUT AGE AS A COMMON DATA ELEMENT. IT COULD BE CONSIDERED TIME SINCE BIRTH, COULD BE DESCRIBED BY CERTAIN PARAMETERS, BIRTH TO 6 MONTHS, UP TO 18 YEARS, ET CETERA. SO THESE ARE CATEGORICAL DESCRIPTIONS OF AGE, IT COULD ALSO BE A CONTINUOUS TIME. THE CDE THAT IS A COMMON DATA ELEMENT OF AGE IS REFLECTED OF AND/OR INTERPRETED BY THE CONCERNS OF AGING PERSONS. THAT IS WE WANT TO MAKE SURE WE LOOK ACROSS OUR FIELDS PROPERTILY AND --APPROPRIATELY AND UNDERSTAND THE WAY THAT INVESTIGATOR CAPTURES AGE AT THE POINT OF ENROLLING A PERSON IN THIS STUDY MAY BE QUITE DIFFERENT THAN A PERSON REPORTS AGE IN THE CLINICALTRIALS.GOV REPOSITORY OR IN TABLE 1 OF A RESEARCH PROJECT. REMEMBER AS WE'RE TALKING ABOUT CLINICALTRIALS.GOV, WE'RE TALKING ABOUT APPLICABLE CLINICAL TRIALS. NEXT SLIDE. APPLICATION TRIALS ARE DEFINED BY REGULATION, THESE ARE GENERALLY NIH FUNDED RESEARCH PROGECS OR RESEARCH THAT IS IN SUPPORT OF FDA APPLICATIONS. LET ME TELL YOU A LITTLE BIT ABOUT WHAT'S BEEN GOING ON IN CLINICALTRIALS.GOV THE LAST COUPLE OF MONTHS. IN ACCIDENT SLIDE, PLEASE. WE HAVE ALMOST 350,000 CHILDS REGISTERED IN CLINICAL TRIALS.GOSHES V AND OVER 44,000 OF THESE HAVE ALREADY POSTED RESULTS. YOU MAY RECALL AND IF YOU LOOK CAREFULLY AT THE GRAPH TO THE RIGHT, THE SIGNIFICANT LEGISLATION THAT SHAPES CLINICALTRIALS.GOV, AND OF PARTICULAR IMPORTANCE HERE WAS A DECISION MADE IN 2007 WITH FADA THAT WE WOULD REPORT RESULTS. IT ACTUALLY TOOK 10 YEARS TO GET THE REGULATIONS IN PLACE FOR THAT REPORTING. BUT ALSO NOTE ALONG THE WAY THERE WAS CLARIFICATION INCLUDING THE RELEASE OF THE NIH POLICY ON REPORTING PARTICIPANT'S AGE. CLINICALTRIALS.GOV IS A REGISTRY OF RESEARCH STUDIES. NOT ALL STUDIES IN CLINICALTRIALS.GOV ARE FUNDED BY THE NIH, ONLY ABOUT 20% WE RECORD THERE. SO THE WORK I WILL BE REPORTING TO YOU TODAY HAS HA DO WITH CLINICAL TRIALS THAT ARE REQUIRED BUT APPLICABLE CLINICAL TRIALS THAT ARE REGISTER INDEED THE C LINICALTRIALS.GOV OPERATION. NEXT SLIDE, PLEASE. AT THE POINT OF REGISTRATION FOR CLINICALTRIALS.GOV WE ARE BRINGS IN INFORMATION ABOUT TRIALS THAT MIGHT BE INCENTIVIZING INDIVIDUALS TO PARTICIPATE IN RESEARCH, SO ON THE SCREEN YOU SEE IN FRONT OF YOU, HERE'S A SAMPLE OF OUR USERS WITH OUR OVER 3 AND HALF MILLION VISITORS MONTHLY. ABOUT 40% ARE PATIENTS AND CAREGIVERS WHO MAY BE LOOKING FOR A STUDY TO PARTICIPATE IN FOR THEMSELVES OR FOR OTHERS. ABOUT 51% ARE RESEARCHERS AND OTHERS INCLUDING--CATEGORIZATION IS. NEXT SLIDE, PLEASE. SO NOW I WANT TO TALK SPECIFICALLY ABOUT HOW WE'RE DEALING WITH INFORMATION IN CLINICALTRIALS.GOV IN SUPPORT OF INCLUSION ACROSS THE LIFESPAN. NEXT SLIDE, PLEASE. THE MOST IMPORTANT POINT OF RECORDING OF INFORMATION REGARDING AGE IS AT THE POINT OF REGISTRATION OF A TRIAL, THAT IS INFORMATION THAT IS SUBMITTED A TRIAL INITIATION. CLINICALTRIALS.GOV HAS 1 STUDY, 1 TRIAL RECORD FOR EACH PARTICULAR STUDY. AND THE DOCUMENTATION INCLUDES KEY PROTOCOL DETAILS INCLUDING THE STUDY DESIGN, THE CONDITIONS OF INTEREST, THE INTERVENTIONS PROPOSED, ANY OUTCOME MEASURES. IT INCLUDES INFORMATION ABOUT RECRUITMENT INCLUDING ELIGIBILITY CRITERIA, STUDY LOCATIONS, AND CONTACT INFORMATION FOR ENROLLMENT. IMPORTANTLY, SECONDARY IDs INCLUDING THE NIH FUNDING OR OTHER FUNDING NUMBERS ARE INCLUDED AT THIS TIME AND ON THE RIGHT HAND SIDE, YOU SEE A BRIEF SUMMARY OF A TRIAL THAT HAS ALREADY BEEN RECORDED. LET ME JUST PAUSE FOR A MINUTE AND CALL YOUR ATTENTION TO THE SMALLER BOX IN THE LEFT-HAND SIDE, THE STUDY--THE SAFETY AND SCIENTIFIC VALIDITY OF THIS STUDY IS THE RESPONSIBILITY OF THE STUDY SPONSORS AND INVESTIGATORS LISTING A STUDY DOES NOT MEAN IT'S BEEN EVALUATE BIDE THE U.S. FEDERAL GOVERNMENT. READ OUR DISCLAIMER HERE. THIS IS AN IMPORTANT ADDITION THAT'S HAPPEN INDEED CLINICALTRIALS.GOV IN THE LAST 3 YEARS. WE'VE BEEN ASKED TO MAKE IT CLEAR THAT THE INDIVIDUAL WHO'S SEEKING INFORMATION IN CLINICALTRIALS.GOV NEEDS TO REMEMBER THIS IS NOT AN ENDORSEMENT BY THE FEDERAL GOVERNMENT BUT RATHER A SERVICE OF THE FEDERAL GOVERNMENT TO HOUSE AND MAKE ACCESSIBLE TO THE SCIENTIFIC AND LAY PUBLIC INFORMATION ABOUT CLINICAL TRIALS. AT THE POINT OF REGISTRATION--NEXT SLIDE PLEASE--AN INVESTIGATOR OR THAT INVESTIGATOR'S DELEGATE MUST PROVIDE INFORMATION ABOUT THE INTENDED RECRUITMENT SPAN OF PARTICIPANTS. THE ELIGIBILITY CRITERIA AND THAT'S WHERE THIS INFORMATION ABOUT AGE IS RECORDED, MUST INCLUDE THE AGE LIMITS OF POTENTIAL PARTICIPANTS AND USUALLY IT'S RECORDED AS A MINIMUM AND MAXIMUM AGE AND USUALLY RECORDED AS A--IN A UNIT OF TIME THAT IS RELEVANT TO THE STUDY WHICH MAY BE YEARS FOR ADULTS OR MONTHS IF THE PARTICIPANTS ARE CHILDREN. SO IF YOU NOTICE ON THE RIGHT HAND SIDE, YOU WILL SEE HOW THE ELIGIBILITY CRITERIA APPEARS, AGE IS ELIGIBLE FOR STUDY, UP TO 70 YEARS, CHILD, ADULT AND OLDER ADULT. AND THEN AGAIN THERE'S ADDITIONAL ELIGIBILITY CRITERIA, SEX IS ELIGIBLE FOR STUDY, ALL, AND WHETHER OR NOT HEALTHY VOLUNTEERS ARE ACCEPTED. ONE IS ABLE TO PUT IN AN ADDITIONAL MORE SPECIFIC INFORMATION ABOUT AGE BEYOND THE CATEGORS YOU SEE, CHILD AND IN TERMS OF GROUPING WE CAN IDENTIFY CHILD BIRTH-17, ADULTS 18-64 OR OLDER ADULTS BEYOND THAT OR WOKNOW CAN IDENTIFY THE AGE IN A SELF-ENTERED NUMERICAL FIELD AS SHOWN ON THE LEFT-HAND SIDE. THE AGE INFORMATION IS REQUIRED BY REGULATIONS 42 CFRPART 11 AND THE NIH POLICY ON DISSEMINATION FUNDED CLINICAL TRIALS INFORMATION. I MUST PAUSE AND POINT OUT HERE THAT IN OUR REGISTRATION WHEN WE COLLECT ELIGIBILITY CRITERIA, AGE IS 1 OF THE FEW STRUCTURED ENTRY OPTIONS THAT EXIST. MOST OF OUR INFORMATION IS ENTERED IN UNSTRUCTURED FASHION. NEXT SLIDE, PLEASE. HERE YOU SEE WHEN THE RESULTS ARE REPORTED AFTER THE TRIAL IS COMPLETED, WE PREPARE A TABLE THAT DESCRIBES THE SUMMARY RESULTS OF THE PARTICIPANT FLOW, THE BASE LINE CHARACTERISTICS, THE PRIMARY AND SECONDARY OUTCOMES INCLUDING STATISTICAL ANALYSIS, ADVERSE EVENTS AND THE PROTOCOL AND STATISTICAL ANALYSIS PLAN WHICH IS ONLY REQUIRED SINCE THE TIME OF JANUARY OF 2017. PLEASE NOTE IN THE CENTER, BLUE CATEGORY THAT THE BASE LINE CHARACTERISTICS DESCRIBES THE NUMBER OF PARTICIPANTS AND THE AGE AND PLEASE NOTE THAT THIS CHART REQUIRES THAT WE DESCRIBE THE AGE, USUALLY AN AVERAGE AGE BY THE VARIOUS ARMS OF THE STUDY, SO IN THIS PARTICULAR STUDY WE HAVE DRUG A, DRUG B AND PLACEBO, THE RIGHT HAND COLUMN SERVING AS A TOTAL. IN ACCIDENT SLIDE, PLEASE. AGE RELATED INFORMATION CAN--REQUIRES THAT WE PROVIDE BASE LINE INFORMATION TO INCLUDE THE AGE TO CHARACTERIZE THE OVERALL STUDY IN THE AGE FORM. WE CAN EITHER USE 1 OF THE 3 OPTIONS, CONTINUOUS WITH MEAN OR MEDIAN AGE, MEASURE OF DISPERSION, CATEGORICAL WHICH IS AL--INFORMATION ABOUT AGE THIS, IS A [INDISCERNIBLE] TRIAL WHICH INCLUDED A CERTAIN NOB OF PARTICIPANTS IN THEIR AVERAGE AGE AND STANDARD DEVIATION IS REPORTED HERE. NEXT SLIDE, PLEASE. IN THE STUDIES, LOOKING AT THE 43,000 STUDIES THAT ALREADY HAVE RESULTS POSTED AS OF JUNE OF THIS YEAR, 72% HAVE AGE AS A CONTINUOUS VARIABLE. NEXT SLIDE, PLEASE. NEXT SLIDE, PLEASE. THIRTY-FIVE% REPORTED AGES CATEGORICAL. NEXT SLIDE, PLEASE, AND 10% REPORTED AGE IN A CUSTOMIZED FASHION FOR EXAMPLE, SPECIFIC SPANS OF MONTHS OR YEARS. OF THESE STUDIES, IF AGE WAS NOT PROVIDED AS A CATEGORICAL VARIABLE, IT'S MUCH MORE DIFFICULT TO UNDERSTAND THE INCLUSION ACROSS THE LIFE SPAN AND TO BE ABLE TO COMPARE STUDIES AND THAT BASICALLY MEANS IF WE'RE ONLY REPORTING AGE AS A MEAN IN THE STANDARD DEVIATION, IT'S VERY DIFFICULT TO DETERMINE THAT WE'RE ACTUALLY MEETING THE L LEVER SPAN EXPECTATION--LIFESPAN EXPECTATIONS. [AUDIO CUTS OUT ]--INVESTIGATOR CAN ACTUALLY SUBMIT ALL 3 DIFFERENT TYPES OF AGE REPORTING. NEXT SLIDE PLEASE. I'VE GIVEN YOU A LOT OF INFORMATION, I'D LIKE TO SHOW YOU A LITTLE BIT ABOUT WHY THIS INFORMATION IS VALUABLE TO US AND HOW AND SOME OF THE WAYS WE MAKE USE OF IT. SO, THIS IS OUR RESULTS OF LANDSCAPE ANALYSIS THAT HAVE BEEN DONE BY THE CLINICALTRIALS.GOV STAFF HERE AT THE NATIONAL LIBRARY OF MEDICINE. NEXT SLIDE, PLEASE. ON THE SCREEN IN FRONT OF YOU, WE'RE ILLUSTRATING THE CLINICALTRIALS.GOV RECORDING AGE SPECIFIC INFORMATION PROVIDES INSIGHTS INTO SPECIFIC PEDIATRIC RESEARCH. NEXT SLIDE, PLEASE. NEXT SLIDE, PLEASE, SO YOU WILL NOTE ON THE RIGHT HAND SIDE AND THE STUDY BY NEAL SPONSORSHIP OF ONCOLOGY CLINICAL TRIALS IN THE U.S. ACCORDING TO THE AGE OF ELIGIBILITY, THE CONCLUSION REPORTS THAT INTERVENTIONAL ONCOLOGY TRIALS THAT INCLUDE PATIENTS UNDER 18 YEARS OF AGE ARE LESS LIKELY TO BE INDUSTRY-SPONSORED AS COMPARED TO ONCOLOGY TRIALS EXCLUSIVE OF PATIENTS 18 YEARS OF AGE AND OLDER. SO THIS GIVES YOU AN EXAMPLE OF HOW HAVING ACCESS TO THIS INFORMATION ACTUALLY ALLOWS US TO DELVE MORE DEEPLY INTO THE STRUCTURE OF CLINICAL TRIALS INFORMATION. ON THE LEFT HAND SIDE OF THE SCREEN, YOU SEE A SUMMARY OF A PEDIATRIC TRIALS RUN AN ANALYSIS FROM THE CLINICALTRIALS.GOV IS THE NOTATION FROM THIS WAS SPECIFICALLY NOTE THAD THE THERAPEUTIC TRAILS IN INDIA WERE APPROPRIATE TO THE PUBLIC NEEDS OF THE COUNTRY'S PUBLIC HEALTH BECAUSE THE AGE INFORMATION WAS AVAILABLE TO DEMONSTRATE WE WERE PROVIDING STUDIES ACROSS THE ENTIRE LIFESPAN. NEXT SLIDE, PLEASE. I'M SORRY, PLEASE CONTINUE. NOW HERE'S A VERY DIFFERENT USE OF AGE INFORMATION IN CLINICALTRIALS.GOV AND THIS MAY BE MORE FAMILIAR TO THOSE OF WHO YOU HAVE BEEN WATCHING THE PUBLIC CONSIDERATION OF HOW THE COVID-19 TRIALS ARE BEING REPORTED. THE NEW YORK TIMES IN JUNE OF THIS YEAR TOOK THE CLINICALTRIALS.GOV REPOSITORY WHICH IS OPEN AND ACCESSIBLE TO THE PUBLIC AND EXAMINED WHETHER OR NOT OLDER ADULTS ARE BEING ADEQUATELY ENGAGED IN VARIOUS TRIALS AROUND THE COUNTRY. IN THIS PARTICULAR EXAMPLE WHAT YOU SEE IS THAT THE AUTHOR LOOKED AT 214 INTERVENTIONAL COVID-19 STUDIES THAT TOOK PLACE IN THE UNITED STATES AND WERE LISTED IN THE NIH RESOURCE CLINICALTRIALS.GOV AND FOUND THAT 37 OF THESE TRIALS, THAT IS OVER 12% OF THEM WOULD NOT ENROLL PATIENTS OVER 75 AND SOME HAD EVEN EXCLUDED PATIENTS OVER THE AGE OF 65. ANOTHER GROUP OF 27 TRIALS SET NO MAXIMUM BUT YOU STUDY DESIGNS MIGHT DISQUALIFY OLDER ADULTS. SO IN ADDITION TO USING OUR CLINICALTRIALS.GOV REPOSITORY AS A WAY FOR BETTER UNDERSTANDING THE SCIENTIFIC ISSUES AND THE ADEQUACY OF CLINICAL TRIALS, WE ALSO ARE PROVIDING A PUBLIC SERVICE THAT IS REPORTERS, GENERAL SCIENCES AND SCIENTISTS ARE ABLE TO ELECTRIC AT OUR RESOURCE TO UNDERSTAND HOW WE'RE SERVING THE PUBLIC. IN --NEXT SLIDE, PLEASE. I WANT TO SAY THAT CLINICALTRIALS.GOV DOES SELECT SPECIAL ISSUES WHERE AGE IS A REALLY DIFFICULT ISSUE TO CHARACTERIZE. SO FOR EXAMPLE, IN CLUSTER RANDOMIZED TRIALS WHERE WE'RE LOOKING AT THE UNIT OF ANALYSIS BEING A GROUP OR CLUSTER OF PARTICIPANTS, INDIVIDUALS IN A NURSING HOME OR PARTICIPANTS IN A COMMUNITY BASED CARE INTERVENTION, AGE RELATED--[AUDIO CUTS OUT ]--OR MORE HOW TO MORE EFFECTIVELY DESCRIBE AGE WHEN THE UNIT OF ANALYSIS IS NOT AN INDIVIDUAL PERSON. IN ADDITION, STUDIES INVOLVING MORE THAN 1 TYPE OF PARTICIPANT IN THE ANALYSIS POPULATION ALSO MAKE IT DIFFICULT TO PROVIDE BRIEF DESCRIPTIONS ABOUT AGE FOR EXAMPLE IN MOTHER-INFANT DYADS THERE'S NO AVERAGE AGE OF A MOTHER AND INFANT TOGETHER, THEY EACH HAVE THEIR OWN AVERAGE AGE BUT BEING ABLE TO MATCH THE DYADS IS REALLY WHAT IS OF MOST INTEREST IN MANY OF THESE STUDIES SO KNOWING THE IMPACT OF OLDER MOTHERS ON THE HEALTH OF YOUNG CHILDREN FOR EXAMPLE REQUIRES THAT WE BE ABLE TO ACCURATELY MATCH, NOT JUST THE AVERAGE AGE OF THE MOTHER AND THE AVERAGE AGE OF THE INFANTS BUT THE EXACT DYAD AGE OF MOTHERS AND INFANTS. NEXT SLIDE, PLEASE. IN A CLUSTER RANDOMIZED TRIAL, HERE'S AN EXAMPLE WHERE AN INTERVENTION WAS COMPARING COMMUNITIES RANDOMIZED TO RECEIVE ANTIBIOTICS AND THE HYPOTHESIS WAS THAT MASS AZITHROMYCIN TREATMENT WAS REDUCE CHILD MORTALITY AND IF YOU LOOK DOWN AT THE PARTICIPANTS IN THIS STUDY, THERE'S 190,000 CHILDREN CLUSTERED ACROSS 1500 DIFFERENT COMMUNITIES. AND THE WAY THE AGE IS REPORTED IN EACH OF THESE, ACORRING TO THE TABLES I SHOWED YOU A FEW SLIDES AGO ACTUALLY DESCRIBES AGES OF CHILDREN AT VARIOUS STAGES BIRTH TO 1 TO 5 MONTHS, 6 TO 11 MONTHS, 12 TO 23 MONTHS AND 24-59 MONTHS. BUT THOSE PARTICIPANTS ABOUT 90,000 OR SO IN EACH CLUSTER ARE ACTUALLY CLUSTERED WITHIN 750, TO 760 DIFFERENT COMMUNITIES. SO THE INTERPRET AITIONZ OF AGE HERE IS A LITTLE BIT DIFFICULT SINCE THE UNIT OF ANALYSIS IS THE COMMUNITY CLUSTER. NEXT SLIDE, PLEASE. HERE WE'RE SHOWING AND REPORTING WITH MULTIPLE PARTICIPANT AND THIS IS THE EXAMPLE OF OUR MOTHERS AND CHILDREN, A RANDOMIZED TRIAL PLAN--PLANNED AMONG ETHICALLY DIVERSE, OVERWEIGHT, OBESE OR PREGNANT WOMEN, RANDOMLY ASSIGNED TO AN INTERVENTION BUT THE OUTCOME IS THE GUESTATIONAL WEIGHT GAIN FROM BASE LINE AND THE STATUS OF THE PREGNANTY SO WE HAVE THE AGE--THE INFORMATION ABOUT THE PARTICIPANTS DISTRIBUTED ACROSS THE VARIOUS GROUPS AND THE 2 INTERVENTIONS ISSUES USUAL CARE AND LIFESTYLE. NEXT SLIDE PLEASE. THE LAST EXAMPLE OF THE WAY WE USE OUR AGE RELATED NFGZ IS TO TAKE THE ELIGIBILITY CRITERIA AND WORK ON MATCHING PATIENTS TO TRIALS. WE DO KNOW THERE'S BEEN INADEQUATE PARTICIPATION OF TRIALS ACROSS THE COUNTRY. WE WOULD LIKE TO INCREASE PARTICIPATION, PROVIDING A TOOL AT THE POINT OF KACCT IRB AND EXAMININE THE METHOD AND WHAT TOOLS THE PATIENT MIGHT BE ELIGIBLE FKD BE A POSSIBILITY BUT AS I REPORTEDDER, AGE IS SOMETHING WE MAINTAIN CATEGORICALLY ON PARTAIS INHIBITOR PANTS AND MUCH OF OUR OTHER ELIGIBILITY KRIST TERRAIA IS DESCRIBED FROM THE PERSPECTIVE OF THE CLINICIANS VIEW POINT IS NEEDED. FOR EXAMPLE, PEOPLE OF XEKD DEGREE RELATIVES WITH LIKE BREAST CANCER OR THOSA UNDER THE AGE OF FIRST REQUIRES MORE INTERPRETATION AND CAN'T BE INTERPRETED BY A MACHINE. SO WE'RE WORKING ON NEW STRATEGIES TO IMPROVE THE RECORD AND ELIGIBILITY CRITERIA. PLEASE GO TO SLIDE 75 AND LET ME THANK YOU FOR YOUR ATTENTION AND HOPE THAT I DEMONSTRATED TO YOU THAT LAWN MOWER WE'RE PROVIDING FOR PATIENTS IN THE USE OF CLINICALTRIALS.GOV IS A WAY TO DEMONSTRATE INCLUSION ACROSS THE LIFE SPAN IS APPEARING TO BE EFFECTIVE. WE'RE ABLE TO CAPTURE THE INFORMATION AND IT APPEARS TO BE GETTING USE. I'M HAPPY TO ANSWER ADDITIONAL QUESTIONS NOW OR MY CONTACT INFORMATION IS AVAILABLE ON THE SCREEN IN FRONT OF YOU. THANK YOU VERY MUCH. NTHERE IS TIME FOR A COUPLE OF QUESTIONS. ONE QUESTION IS THERE IS A LOT OF HETEROGENEITY WITHIN THE HEALTH POPULATION THAT IS OVER THE AGE OF 65. I WONDER WHAT SHE THINKS THE 10 YEAR INCREMENTS RATHER THAN THE CAT GOORY IS FOR GREATER THAN 65. >> [COUGHING ] EXCUSE ME, WE VERY MUCH ARE IN SUPPORT OF HAVING AGE CATEGORIES THAT ARE PARTICULARLY REFLECTIVE OF THE CLINICAL PHENOMENON THAT IS OF INTEREST. RIGHT NOW THE REQUIREMENT AT THE NIH ONLY SPECIFIES THAT WE MUST IDENTIFY AGE AT THE BEGINNING OF A STUDY, THE BASE LINE DESCRIPTION AND THEN FOR APPLICABLE CLINICAL TRIALS AN AGE TO IDENTIFY THE ARM OR A MEDIAN AGE OR DESCRIPTION. THAT COULD BE BROKEN DOWN MORE EXTENSIVELY. PLEASE REMEMBER THAT RESULTS DO NOT NEED TO BE REPORTED BY AGE. AND THIS IS A CONTROVERSIAL CONVERSATION WE'VE BEEN HAVING BECAUSE THERE IS A GREAT INTEREST TO UNDERSTAND IF THERE WAS A DIFFERENTIAL EFFECT--[AUDIO CUTS OUT ]--FROM THE CLINICALTRIALS.GOV PERSPECTIVE IS NOT REPORTING AT A LEVEL OF GRANULARITY THAT LACKS POWER FOR INTERPRETATION, SO IF A STUDY HAS PROPOSED AGE-RELATED ANALYSIS AND EVEN 1 AS GRANULAR AS EVERY 10 YEARS IT WOULD BE APPROPRIATE AND IT WOULD BE POSSIBLE TO REPORT THAT INFORMATION WITHIN OUR CLINICALTRIALS.GOV OPERATION. BUT WE WANT TO BE VERY CAREFUL NOT TO MISLEAD THE PUBLIC BY SUGGESTING THAT 1 COULD COMPARE ACROSS AGES WHEN THE STUDY WAS NOT SUFFICIENTLY POWERED FOR AGE. >> PATTY ANOTHER CHAT QUESTION, THERE IS SOME TALK ABOUT CHALLENGES WITH NOT COMPLETING THAT FINAL REPORT IN CLINICALTRIALS.GOV AND MAYBE SOMETHING THAT YOU AND MIKE WILL WANT TO ADDRESS BUT WHAT ARE THE CONSEQUENCES TO RESEARCHERS IF THEY DON'T ABIDE THAT FINAL REPORT IN CLINICALTRIALS.GOV. >> THERE ARE FINANCIAL AND OPERATIONAL SANCTIONS THAT CAN BE IMPOSED IF A CLINICAL TRIAL DOES NOT COMPLETE THE REPORT WITHIN 1 YEAR OF THE POINT OF THE COMPLETION OF THE LAST PARTICIPANT. THOSE SANCTIONS ARE ALLOWED FOR BOTH AN NIH POLICY AND IN THE FDA FADA REGULATIONS, THE FADA REGULATIONS ARE PRETTY EXPLICIT ABOUT IT, SEVERAL THOUSAND DOLLARS PENALTY PER DAY. WE'VE BEEN CHALLENGED IN THE LITERATURE RECENTLY ABOUT THE FACT THAT STUDY REPORTING IS LAGGING BEHIND WHAT IT SHOULD BE AND THE ENFORCEMENT OF STUDY REPORTING IS OF QUESTION. AND WHAT HAS BEEN DEMONSTRATED MOST RECENTLY IS THAT ENFORCEMENT IS THE RESPONSIBILITY OF THE FDA AND THE NIH AND IT IS OUR RESPONSIBILITY TO INSURE THAT WE ARE ABLE TO PROVIDE THE INFORMATION AS QUICKLY AS POSSIBLE. A KEY CHALLENGE IS THE--INSURING THAT RESULTS ARE REPORTED WITHIN 30 DAYS OF BEING DEPOSITED AND THE CHALLENGE THERE COMES IN FRANKLY IN MAKING SURE THAT THE RESUMMITS ARE CORRECT, HAVE BEEN--RESULTS ARE CORRECT, PROPERLY CURATED AND REPORTED WITH THE RIGHT UNITS OF ANALYSIS. WE DO HAVE--WE HAVE RECENTLY ALONG WITH THE OFFICE OF EXTRAMURAL RESEARCH DEVELOPED A POLICY INTERPRETATION THAT ALLOWS FOR RESULTS ONCE SUBMITTED TO BE REPORTED EVEN BEFORE THEY HAVE BEEN VERIFIED SO THAT INSTITUTIONS ARE ABLE TO MEET THEIR CRITERION OF HAVING THEIR RESULTS REPORTED WITHIN 1 YEAR. WHAT WE DO KNOW IS THAT THE NIH AND THE FDA FRANKLY BENEFITS FROM THE FACT THAT CLINICALTRIALS.GOV EXISTS SO THERE IS A PLACE WHERE THE ACCURACY IS THE COMPLIANCE WITH THESE REGULATIONS CAN BE ASSESSED. IF I MAY, I WOULD LIKE TO CLOSE BY THANKING DR. COLLINS AND THE N NIH LEADERSHIP AND THE CENTER FOR INFORMATION TECHNOLOGIES CAPITAL INVESTMENT FUND FOR THE SUPPORT OF THE MODERNIZATION OF THE CLINICALTRIALS.GOV REPOSITORY. TWO YEARS AGO WE LAUNCHED A 5 YEAR, 30-40 MILLION-DOLLAR REBUILD OF THE CLINICALTRIALS.GOV REPOSITORY RECOGNIZING ITS IMPORTANCE IN THE COUNTRY TO BRING ACRASE MODEL SKPE BAKUGAN TO SCIENTIFIC GROWTH. WE HAVE COMPLETED ABOUT A THIRD OF TD WORK FOR THE FIRST YEAR WE SPENT A GREAT DEAL OF TIME IN SOLICITING TAKE HOLDER INPUT THROUGH A REQUEST FOR INFORMATION AND THROUGH PUBLIC HEARINGS, WE WILL CONTINUE TO ENGAGE WITH THE UBIQUITINNATION PUBLIC THROUGH A WORKING GROUP WITH THE BOARD OF REGENTS FOR THE NATIONAL LIBRARY OF MEDICINE, IMPORTANTLY SHOULD YOU HAVE IDEAS ABOUT THE OPERATIONS CLINICALTRIALS.GOV, THE RESULTS REPORTING, SOME SUGGESTIONS FOR US ABOUT WHAT WOULD MAKE IT BET ARE FOR YOU, WE WOULD BE VERY INTERESTED IN HEARING THIS. WHILE OUR OPERATION AND MODERNIZATION REALLY IS ON THE BACK END MAKING SURE THAT THE DATA REPOSITORIES ROBUST AND WELL CONNECT WIDE OTHER NLM SERVICES WE DO KNOW THE FRONT END IS WHERE PEOPLE MOSTLY CONNECT WITH THE NATIONAL LIBRARY OF MEDICINE'S RESOURCES AND IF YOU HAVE IDEAS FOR US ABOUT HOW TO MAKE THAT EASIER, MORE EFFICIENT FOR INVESTIGATORS TO INTERACT WITH OR MORE USEFUL FOR THE PUBLISHING, I WOULD BE QUITE INTERESTED IN HEARING THOSE. THANK YOU VERY MUCH. >> THANK YOU DR. BRENNAN. WE WILL TAKE A PAUSE HERE AND WE WILL RESTART THE PROGRAM AT 12:30 EASTERN STANDARD TIME. AGAIN WE WILL BE START NOTHING 10 MINUTES AT 12:30 EASTERN STANDARD TIME. THANK YOU. >> HELLO AND BACK TO THE INCLUSION ACROSS THE LIFESPAN WORKSHOP. FOR THOSE WHO ARE PARTICIPATING IN THE WORKSHOP VIA THE VIDEOCAST, PLEASE FEEL FREE TO USE THE SUBMIT FEEDBACK BUTTON THAT'S IN THE WEBCAST AT VIDEOCAST TO SUBMIT YOUR COMMENTS OR QUESTIONS. WE WILL NOW BEGIN THE TOPIC OF DISCUSSION FOR INCLUSION AND EXCLUSION CRITERIA. NEXT SLIDE, PLEASE. THIS PANEL IS CHAIRED BY DR. FLORENCE BOURGEOIS AND DR. CYNTHIA BOYD. >> PARTICIPATING IN THE PANEL, OUR FIRST PANEL IS CLINICAL RESEARCH INCLUSION AND EXCLUSION CRITERIA AGAIN I AM DR. BOURGEOIS, AND AM AN ASSOCIATE PEDEIAT MEDICINE AT% HARCARD MEDICAL SCHOOL AND I WORK ON SUPPORTING INFRASTRUCTURE AND SUPPORTING PEDIATRIC TOOLS. WOULD ALSO LIKE TO INTRODUCE 2 OF OUR PANELISTS. FIRST WE HAVE DR. LUCILE, ADAMS-CAMPBELL COMMUNITY ASSOCIATE DEAN IN COMMUNITY OUTREACH ENGAGEMENT, PROFESSOR OF AT LOMBARDI UNIVERSITY OF GEORGE TOWN MEDICAL CENTER ASK IS TALKING ABOUT ENHANCING POPULATIONS OF MINORITY POPULATIONS IN CLINICAL TRIALS. WE ARE ALSO JOINED BY DR. GEORGE SAADE, SHE IS THE JEANE, DISTINGUISHED PROFESSOR OF CELL BIOLOGY AND UNIVERSITY OF TEXAS MEDICAL BRANCH AND HIS RESEARCH IS FOCUSED ON ADVERSE PREGNANCY OUTCOMES AND THE LONG-TERM HEALTH OF MOTHER AND CHILD. DR. BOYD? >> GREAT. AND I TOO WANT TO SHARE MY THANKS FOR THE NIH PUTTING THIS PANEL ITTH AND FOR MY ABILITY TO PARTICIPATE. I AM A PROFESSOR EVER MEDICINE AT JOHNS HOPKINS UNIVERSITY IN THE DIVISION OF GERIATRIC MEDICINE AND GERONTOLOGY AND MY WORK IS FOCUSED ON THE INCLUSION OF OLDER ADULTS, PARTICULARLY THOSE WITH MULTIPLE CHRONIC CONDITIONS IN RESEARCH ACROSS THE TRANSLATIONAL PATH. I'M DELIGHTED TO BE INTRODUCING 2 OF OUR PANELISTS, DR. SEALIA FISHER IS THE MARIE WORD UNIVERSITY CHAIR IN ETHICS AND PROFESSOR OF PSYCHOLOGY AT FORDHARM UNIVERSITY AND SHE DIRECTS THE HIV DRUG PREVENTION AND RESEARCH TRAINING INSTITUTE AND HAS 20 YEARS OF EXPERIENCE CONDUCTING RESEARCH ON ETHICAL ISSUES AROUND ADOLESCENT HEALTH INCLUDING VULNERABLE POPULATIONS WITH SPECIAL ATTENTION TO BARRIERS AND FACILITATORS. WE ARE ALSO JOINED BY DR. WILLIAM DALE WHO IS THE FAMILY CHAIR IN SUPPORTIVE CARE MEDICINE AND DIRECTOR OF THE CENTER FOR CANCER AND AGING AT CITY OF HOPE'S COMPREHENIVE CANCER CENTER. HE'S A GERIATRICIAN AND PALLIATIVE MEDICINE PHYSICIAN DOING CANCER AND AGING WERE THROUGH THE CANCER AND AGING RESEARCH GROUP AND FOCUSED ON OLDER ADULTS WITH CANCER, PARTICULARLY THOSE WITH FUNCTIONAL LOSSES AND COGNITIVE IMPAIRMENT. WE'RE DELIGHTED TO HAVURE OUR PANEL WITH US--HAVE OUR PANEL WITH US TODAY. DR. BOURGEOIS? YOU ARE MUTED. >> AS A QUICK OVERVIEW OF HOW WE WILL BE PROCEEDING BOTH MYSELF AND DR. BOYD BOYD WILL BE GIVURE EXPETERS ON PODDULATIONS IN PEDIATRIC END AND ALSO GERIATRIC END AND FOLLOWING THIS WE WILL HAVE OUR PANELISTS SPEAK TO THE ISSUES OF INCLUSION ACROSS AGES AND PARAMETERS BASED ON THEIR BACKGROUND AND WORK AS CLINICAL TRIALISTS. AFTER THAT, DR. BOYD AND MYSELF WILL ASK A FEW QUESTIONS OF OUR PANELISTS ANDA THE THAT STAGE WE WILL BE OPENING IT UP TO QUESTIONS. SO PLEASE FEEL FREE TO SEND QUESTIONS IN THROUGH THE CHAT AND WE WILL HAVE TIME TO ADDRESS THOSE WITH OUR PANELISTS. NEXT SLIDE, PLEASE. SO MY EXPERTISE IS IN PEDIATRICS AND SPECIFICALLY LOOKING AT THE INCLUSION OF CHILDREN IN PEDIATRIC TRIALS AND I WANTED TO IN THE WAY OF INTRODUCTION HIGHLIGHT THIS FIGURE HERE WHICH KHI IS A NICE DEMONSTRATION OF CLINICAL TRIAL ACTIVITY OVER THE LAST 50 YEARS OR SO. AS YOU CAN SEE FROM THE LAVENDAR LINE WHAT'S BEEN A RAPID UPTICK IN RANDOMIZED TRIALS AND CLINICAL TRIALS IN GENERAL ACROSS ALL AGE GROUPS BUT THIS HAS NOT BEEN REFLEBT INDEED THE PEDIATRIC POPULATION SPECIFICALLY. SO IF YOU LOOK AT THE DARK BLUE LINE THE RATE OF INCREASE HAS BEEN STAGINENT WITH AN EVER-INCREASING GAP WITH TRIAL ACTIVITY IN ADULTS AND CHILDREN. THE REASON THIS MATTERS IS BECAUSE THIS CONTRIBUTES TO THE CLINICAL CARE AND EVIDENCE WE HAVE WHEN WE'RE TREATING CHILDREN AND AS AN EXAMPLE IF YOU THINK OF MEDICATIONS SPECIFICALLY, IT'S ESTIMATED THAT ABOUT 52% OF DRUGS DO NOT CURRENTLY HAVE PEDIATRIC PRESCRIBING GUIDELINES. SO AS PHYSICIANS WE EXTRAPOLATE FIND FRTION ADULT STUDIES AND USE THOSE PRODUCTS IN CHILDREN WITHOUT AGE-SPECIFIC RESEARCH ON DOSING. NEXT SLIDE, PLEASE. THERE ARE A NUMBER OF BARRIERS TO THE INCLUSION OF CLINICAL TRIALS AND MANY OF THEM ARE JUSTIFIED. THEY ARE PRINCIPALLY CENTERED ON ETHICAL AND LEGAL CONSIDERATIONS AND TO THE FINANCIAL CONSIDERATIONS AND INCENTIVIVES FROM THE PERSPECTIVE OF SPONSORS SO IN TERMS OF THE ETHICAL AND LEGAL CONSIDERATIONS IN THE U.S., THERE'S SPECIFIC GUIDANCE AROUND THE TYPES OF RISK THAT CHILDREN MAY BE EXPOSED TO. AND SPECIFICALLY RESEARCH MUST INVOLVE NO MORE THAN MINIMAL RISK TO THE CHILD OR IF IT DOES, 1 OF 3 CRITERIA NEED TO BE MET AND THESE ARE--THEY MUST BE PRESENT POTENTIAL FOR DIRECT BENEFIT TO THE CHILD OR THE RESEARCH MUST BE LIKELY TO YIELD GENERALIZABLE KNOWLEDGE ABOUT THE PARTICIPANTS CONDITION OR IT MUST PRESENT AN OPPORTUNITY TO UNDERSTAND, PREVENT OR ALLEVIATE A SERIOUS PROBLEM AFFECTING THE HEALTH OR WELFARE OF CHILDREN. IN TERMS OF FINANCIAL CONSIDERATIONS, HERE WE'RE SEEING HIGHER COSTS TO RECRUITING CHILDREN IN PART BECAUSE OF THESE BARRIERS AND IN PART TO THE FACT THAT CHILDREN WHO ARE ILL OR REQUIRE A CERTAIN INTERVENTION OR ELIGE FOR CHILD ENROLLMENT IS SIMPLY SMALLER SO CHILDREN IN EFFECT ONLY COMPRISE ABOUT 23% OF OUR POPULATION AND ON AVERAGE ARE HEALTH YEAR, SO IN OLDER TO GET TO A LARGE--ORDER TO GET TO A LARGE SAMPLE SIZE, 1 WE MIGHT SEE IN ADULTS MORE SITES NEED TO BE DROUGHT BROUGHT ON TO TRIALS WHICH CAN INCUR ADDITIONAL COSTS AND IS TIMELY AND RESOURCE INTENSIVE. IN ADDITION THERE ARE LIMITED PROSPECTS FOR PROFITS GIVEN A SMALLER MARKET FOR MANY CONDITIONINGS COMPARED TO ADULTS WHICH IS IMPORTANT FOR PHARMACEUTICAL COMPANIES AND OTHER TYPES OF SPONSORS. NEXT SLIDE, PLEASE. THANK YOU. ONE BACK. APOLOGIES. SO IN TERMS OF THE COVID-19 PANDEMIC THIS IS A NICE ILLUSTRATION OF WHAT'S OCCURRED WITH THE TYPES OF ENROLLMENT CRITERIA THAT WE HAVE IN PLACE. THIS IS A FIGURE FROM A PUBLICATION THAT WE HAD BACK IN APRIL AND YOU CAN SEE THAT STARTING IN FEBRUARY AND MARCH WHEN THE PANDEMIC WAS TAKING OFF, THERE WAS WAS VERY RAPID INCREASE IN THE TRIAL CONDUCT, SPECIFICALLY AROUND COVID-19 IN LOOKING AT THE DARK BLUE BARS, YOU CAN SEE THIS UPTICK STARTING FEBRUARY TO APRIL BUT THE NUMBER OF TRIALS OPEN TO CHILDREN WAS SIGNIFICANTLY LESS AND THOSE ARE THE LIGHT BLUE BARS. I UPDATED THIS RECENTLY TO SEE WHEREY WOO ARE NOW AND AS OF AUGUST 27th, THERE WERE CLOSE TO 1800 INTERVENTIONAL STUDIES OVERALL STUDYING COVID-19 TREATMENTS, BUT LESS THAN 10% OF THOSE WERE OPEN TO CHILDREN. SO AGAIN, A NICE ILITRATION IN OUR CURRENT PANDEMIC AGAIN OF THE EXCLUSION KRISTITARY THAT ARE APPLIED IN CLINICAL TRIALS TO PEDEIAT PATIENTS SPECIFICALLY. NEXT SLIDE PLEASE. IN THINKING ABOUT THE NIH POLICY THAT WENT INTO EFFECT IN 2019, THERE ARE 2 CONSIDERATIONS WORTH NOTE NOTHING TERMS OF THE IMPLICATIONS AND THE IMPLICATIONS FOR CHILDREN. THE FIRST IS THAT THE JUSTIFICATION FOR PEDEIAT INCLUSION PLAN MUST BE SCIENTIFICALLY AND ETHICALLY APPROPRIATE AND WELL-DEFINED. THE SECOND 1 IS THAT THE PROPOSED ENROLLMENT OF PEDIATRIC PATIENTS NEEDS TO BE FEASIBLE AND ALSO SCIENTIFICALLY MEANINGFUL AND WHAT I MEAN BY THAT SPECIFICALLY IS THAT SIVENLLY EXTENDING THE LOWER AGE OF ENROLLMENT INTO ADOLESCENCE IN OTHER PEDIATRIC GROUPS MAY NOT BE SUFFICIENT. WE DON'T WANT THIS TO BE MERELY A TOKEN INCLUSION .D FOR MANY INTERVENTIONAL STUDIES INCLUDING CHILDREN IN THE ADULT STUDY MAY NOT BE SUFFICIENT TO ACCOUNT FOR THE UNIQUE ENROLLMENT REQUIREMENTS AND ALSO MAY NOT ADDRESS THE DIFFERENT SCIENTIFIC CONSIDERATION WHEN IS ENROLLING CHILDREN SO THESE MUST BE SEPARATELY ADDRESSED AND IN SOME CASES A SEPARATE PEDIATRIC STUDY WOULD BE MORE APPROPRIATE. IN ADDITION APPROPRIATE PEDIATRIC AGE GROUPS SHOULD ALSO BE INCLUDED SO PEDIATRIC PATIENTS 0 THROUGH ADOLESCENTS ARE NOT EQUIVALENT AND DIFFERENT CONSIDERATIONS MAY APPLY TO AN ADOLESCENT GROUP VERSUS INFANTS OR YOUNG CHILDREN UP TO 5 YEARS OF AGE. NEXT SLIDE, PLEASE. WITH THESE 2 CONSIDERATIONS IN MIND, THEY ALLOW US TO KEEP IN MIND SUCCESSFUL IMPLEMENTATION OF THE NIH POLICY AND THESE GO FROM THE START WITH THE APPLICATION REQUIREMENTS, THE REVIEW REQUIREMENTS AND THEN THE REPORTING AND THE PUBLIC FACING TRANSPARENCY AROUND TRIAL INCLUSION. TO START OUT WITH THE APPLICATION IMPROVES--ACROSS THE PEDIATRIC AGE GROUPS SHOULD ALSO BE INCLUDED AND AGAIN HERE THE IMPORTANCE IS THAT THERE'S SIGNIFICANT CHANGES IN DEVELOPMENTAL AND PATHOPHYSIOLOGY FROM BIRTH TO ADOLESCENTS SO THEY COULD NOT BE INCLUDED EQUIVALENTLY. AND FINAL INFORMATION TO PROPOSE WHETHER IT'S SPHSKLY MEANINGFUL SHOULD ALSO BE INCLUDED. NEXT SLIDE, PLEASE. MOVING TO THE PREAWARDS STAGE, IT'S IMPORTANT TO KNOW THAT THE REVIEW PANELS PLAY A CRITICAL ROLE IN THE IMPLEMENTATION OF THE NIH POLICY AND WITH THIS IN MIND WE NEED TO INSURE THAT THE PROCESS IS THERE TO HAVE APPROPRIATE MEDIATE RICK EXPERTISE ON THE REVIEW PANELS AND PROPOSE THE INCLUSION AND EXCLUSION PLANS IN TERMS OF WHETHER THE CHILDREN ARE--WHETHER EXCLUSION OF CHILDREN IS JUSTIFIABLE AND WHETHER INCLUSION IS SCIENTIFICALLY MEANINGFUL AND WHETHER THE PROPOSED ENROLLMENT PLAN FOR THE SPECIFIC PEDIATRIC AGE GROUPS IS RIGOROUS AND ALSO FEASIBLE. NEXT SLIDE, PLEASE. THE LAST ELEMENT IS AROUND PUBLIC REPORTING AND TRANSPARENCY. SO CURRENTLY THE POLICY REQUIRES THE NIH TO REPORT AT AN AGGREGATE LEVELOT INCLUSION OF RELEVANT CATEGORIES EVERY 3 YEARS IN THE TRI-ANNUAL REPORT. THERE MAY BE BEN NITRIC OXIDE IN ALSO PROVIDING STUDY LEVEL DATA ON AGE BASED INCLUSION/EXCLUSION IN A MORE TIMELY FASHION AND THIS COULD BE PROVIDED ON NIH REPORTER OR IN CLINICALTRIALS.GOV AND AS WE JUST HEARD FROM DR. BRENNAN THERE IS ALREADY AMPLE INFORMATION PROVIDED ON PEDIATRIC AGE GROUPS BUT THIS COULD BE AUGMENTED WITH INFORMATION ON THE EXPECTED OR PROPOSED INCLUSION OF CHILDREN. SO THE SAMPLE SIZE, THE NUMBER OF CHILDREN WHO ARE ANTICIPATED TO BE ENROLL INDEED A TRIAL SAY THAT IS OPEN TO 12-40 YEAR-OLDS. THE BENEFIT OF THIS IS THAT THAT ENABLING THE SCIENTIFIC COMMUNITY TO PERFORM MORE PREQUENT ANALYSIS OF THE SUCCESS OR IMPACT OF THE POLICY AND ALLOW IDENTIFICATION OF OPPORTUNITIES AND PERSISTENT BARRIERS TO INCLUSION. NEXT SLIDE, PLEASE. SO IN SUMMARY, POLICY NOW REQUIRES THE NIH AT THE APPLICATION STAGE, PREAWARD REVIEW POINT AND AT THE LEVEL OF REPORTING AND PUBLIC DISCLOSURE, POST FUNDING AND SECONDLY, EVIDENCE-BASED IMPROVEMENTS TO THE IMPLEMENTATION WILL BE FACILITATED BY STUDY LEVEL, REALTIME PUBLIC REPORTING ON AGE BAGSED INCLUSION AND EXCLUSION PLANS, RATIONALS AND EVENTUAL ENROLLMENT. THANK YOU VERY MUCH. SO THAT CLOSES MY INTRODUCTION. I'M FOR PEDIATRIC CONSIDERATIONS AND I WILL HAND IT OFF TO DR. FOID TO PROVIDE THE GERIATRIC PERSPECTIVE. >> THANK YOU. ARE I WILL BE SPEAKING ABOUT THE INCLUSION OF OLDER ADULTS IN CLINICAL RESEARCH INCLUDING CLINICAL TRIALS AS WELL AS OTHER OBSERVATIONAL STUDIES. NEXT SLIDE, PLEASE. SO AS WE'VE HEARD FROM A NUMBER OF SPEAKERS TODAY, A FUNDAMENTAL QUESTION WHEN WE'RE THINK BEING HOW WE APPLY RESEARCH TO THE CHAIR AND OF POPULATIONS IS ARE THE PARTICIPANTS IN THE RESEARCH REPRESENTATIVE OF THE ACTUAL POPULATION THAT HAVE THE CONDITION OR CONDITIONS OF INTEREST. IN GENERAL, THE POPULATION IS OFTEN UPON OLDER AND WITH MORE MULTIPLE CHRONIC CONDITIONS THAN THE POPULATION THAT IS INCLUDED IN CLINICAL STUDIES. OVER THE PAST DECADE, THE NUMBER OF TRIALS WITH EXPLICIT AGE INCLUDE EXCLUSIONS HAS DECREASED AND THIS HAS LED TO AN INCREASED TRIAL ENROLLMENT OF OLDER PATIENTS BUT I THINK PART OF THE IMPETUS OF THE CHANGE IN POLICY IS THIS IS STILL WELL BELOW THE LEVELS THAT ARE OLDER PATIENTS ARE ACTUALLY AFFECTED BY THE CLINICAL SITUATIONS THAT ARE BEING STUDIED. OVER THE SAME PERIOD OF TIME, WE'VE ALSO SEEN THAT AS AGE INCLUSIONS HAVE GONE AWAY, 1 EXAMPLE IS FOR HEART FAILURE TRIALS, THERE'S BEEN AN INCREASE IN THE NUMBER OF TRIALS THAT EXCLUDED PEOPLE WITH SPECIFIC AND VERY COMMON CO-MORBIDITIES TO HEART FAILURE WHICH AGAIN, ENDS UP FUNDAMENTALLY AFFECTING THE REPRESENTATIVENESS AND THE ABILITY TO APPLY THE RESEARCH. NEXT SLIDE, PLEASE. THIS WORK WHICH WAS DONE BY MANY OF THE FOLKS AT THE NIH, WHO ORGANIZED THIS PANEL, I THINK SUMS UP THE ISSUE, WELL. JEROME LOCKET AND COLLEAGUES THEY STUDY THE MEAN AND MEDIAN AGE FOR CLINICAL TRIALS FOR 10 CONDITIONS OVER A PERIOD OF ABOUT 45 YEARS AND THERE WERE OVER 600 TRIALS INCLUDED AND YOU CAN SEE HERE THE MAIN CONDITIONS THAT WERE--IS THAT ONE-THIRD OF THE STUDIES EXCLUDED PEOPLE BY HAVING UPPER AGE LIMITS AND ALL STUDIES HAD SOME EXCLUSION CRITERIA AND THE MOST COMMONLY EXCLUDED CONDITIONS WERE FORMACY OR CONCOMITANT MEDICATIONS, CARDIAC ISSUES AND VARIOUS FORMS OF CANCER AND VARIOUS FORMS OF COGNITIVE IMPAIRMENT. AND THIS IS IMPORTANT BECAUSE AS WE KNOW THE PEOPLE WHO LIVE WITH THESE CHRONIC DISEASES ARE OVERWHELMINGLY HAVE ADDITIONAL CO EXISTING CONDITIONS AND SO, BY EXCLUDING THESE PEOPLE, IT IS 1 WAY OF PRODUCING THE GENERALIZABILITY. WE ALSO KNOW THAT FOR MOST OF THESE CONDITIONS, THE MEAN AGE OF THE POPULATION LIVING WITH THESE CONDITION SYSTEM MUCH HIGHER THAN THOSE THAT WERE FOUND IN THE TRIALS. NEXT SLIDE, PLEASE. SO I AM GOING TO SHARE WORK BY COLLEAGUES AND DOCTORS, IN HOW DO WE GET OLDER ADULTS INTO CLINICAL TRIALS. THIS WAS ORGANIZED AROUND THE 5 Ts FRAMEWORK AND I WILL FOCUS IN MY REMARKS ABOUT THE T THAT'S THE TARGET POPULATION AND I THINK MANY OF THESE OTHER THEMES WILL BE SEEN DESPITE OTHER PANELS, BUT FUNDAMENT THAT SHOULD GUIDE INCLUSION, OLDER ADULTS IN CLINICAL RESEARCH IS TO AVOID EXCLUSIONS THAT LIMIT STUDY GENERALIZABILITY AND THAT WE FUNDAMENTALLY NEED TO UNDERSTAND THE PREVALENCE OF THE STUDY CONDITION IN OLDER ADULTS AND ADDITIONAL INFORMATION ABOUT WHO THOSE OLDER ADULTS ARE, WHAT OTHER CONDITIONS, SYNDROMES, DO THEY HAVE. NEXT SLIDE, PLEASE. SO THIS IS SOME DATA THAT HOPEFULLY SHOWS THAT MULTIPLE CHRONIC CONDITION SYSTEM COMMON AND FOR MANY CHRONIC CONDITIONS, IT IS ACTUALLY THE NORM AND NOT THE EXCEPTION. THIS DATA FROM JAMA BY DR. CARLOS WISE AT MICHIGAN STATE AND COLLEAGUES SHOWS THAT AMONG PEOPLE FOR EXAMPLE, OLDER WOMEN LIVING WITH CORONARY HEART DISEASE, ONLY 17% OF THEM HAVE CORONARY HEART DISEASE IN ISOLATION AND DO NOT HAVE ANY OF THE 4 OTHER CONDITIONS THAT ARE LISTED HERE. SPECIAL YOU CAN SEE THAT IS TRUE FOR THESE 5 CONDITIONS UNDER STUDY. AS YOU WOULD IMAGINE IF MORE CONDITIONS WERE CONSIDERED, THE NUMBER OF PEOPLE WHO HAVE THAT DISEASE IN ISOLATION WOULD BE EVEN SMALLER AND AS DR. BERNARD AND COLLEAGUES FROM THE NIH HAVE SAID THAT ENROLLING OLDER PEOPLE IN THESE CLINICAL TRIALS WILL BE NOISIER. NEXT SLIDE, PLEASE. THIS STUDY IS FROM NHANES A FEDERALLY FUNDED VERY LARGE ONGOING RESEARCH STUDY AND 2 PAINTS TO MAKE HERE, THIS IS LOOKING AT OLDER ADULTS WITH JUST CORONARY HEART DISEASE AS AN EXAMPLE AND I WILL NOTE THIS IS LOOKING AT PEOPLE 45 AND OLDER AND THE PART OF THE REASON I INCLUDE THAD IS THAT WE KNOW A LOT OF THE ACCRUAL OF MULTIPLE CHRONIC CONDITION SYSTEM ACTUALLY HAPPENING IN THE AGES OF THE 40S AND 50S AND EARLY 60S. SO BEFORE THE TIME PERIOD WE TYPICALLY THINK ABOUT OLDER ADULTS. THIS IS HOW COMMON THESE CONDITIONS ARE IN THE PEOPLE WHO ARE LIVING WITH CORONARY HEART DISEASE. THE RPGHT KEY PIECE, I THINK TO KEEP IN MIND WHEN WE'RE THINKING ABOUT THE AGE IS THAT WE KNOW THAT MINORITY POPULATIONS, THE SHIFT OF ACCRUING MULTIPLE CHRONIC CONDITIONS IN SOME STUDIES APPEARS TO HAPPEN AT ABOUT 10 YEARS EARLIER. AND SO IT'S A REALLY IMPORTANT ISSUE FOR DISPARITIES, THE OTHER PIECE HERE IS THAT I THINK WE NEED TO MAKE SURE THAT WE'RE THINKING BEYOND THINGS THAT ARE THOUGHT OF AS TRADITIONAL DISEASES AND MAKE SURE THAT WE'RE THINKING ABOUT WHO GETS INCLUDED IN STUDIES THAT WERE RECOGNIZING THINGS THAT MAYBE GERIATRIC SYNDROMES OR THAT AREN'T NECESSARILY THOUGHT OF AS CLEARLY AS A DISEASE. SO FOR EXAMPLE, DIZZY NSZ OR FALLS OCCURS IN MORE THAN 30% OF ADULTS LIVING WITH CORONARY HEART DISEASE AND IT MAY BE CAUSED BIA A MULTITUDE OF REASONS BUT IF MAY AFFECT TYPE, BLOOD PRESSURE CONTROL IN SOME PATIENTS AND MAY END UP AFFECTING THE ABILITY FOR THESE PEOPLE TO BE INCLUDED IN TRIALS THAT HAVE NOT THOUGHT THROUGH THE ISSUES WELL IN ADVANCE LIKE THE NEW POLICY IS ASKING US TO DO. NEXT SLIDE, PLEASE. AND MY FINAL POINT HERE IS THAT GOOD LUCK BACK TO THAT 5 T SPECIFIC FRAMEWORK, IT'S ACTUALLY BASED ON THE 5 Ms FRAMEWORK WHICH COMES FROM THE AMERICAN GERIATRIC SOD AND OTHER GERIATRIC GROUPS AND THE 5 THINGS WE NEED TO KEEP IN MIND. SO WHEN WE'RE THINKING ABOUT MULTICOMPLEXITY WE WANT TO LIMIT EXCLUSIONS, ACCOUNT FOR COMPETING RISKS AND ADDRESS TRADE-OFFS WHEN WE THINK ABOUT WHAT DIFFERENT OUTCOMES THAT MATTER TO PEOPLE WITH DIFFERENT COMBINATIONS OF CONDITIONS. AND THAT WE ALSO NEED TO MAKE SURE WE'RE ADDRESSING--INCLUDING THINGS LIKE HOME VISITS THAT WE NEED TO THINK ABOUTS MEDICATIONS AND INCLUDE NONSTUDIED MED WHEN IS APPROPRIATE AND THERE MAY BE TIMES WHEN IT IS APPROPRIATE TO DE-PRESCRIBE AND ANTICIPATE THAT ADVERSE DRUG EVENTS ARE GOING TO BE COMMON IN THESE STUDIES AND ALSO WE NEED TO INCLUDE OUTCOMES FOR PATIENTS AND STAKEHOLDERS. NEXT SLIDE, PLEASE. SO SUCCESSFUL IMPLEMENTATION OF THE POLICY REALLY REQUIRES US TO BE THINKING ABOUT OLDER ADULTS, IN ALL STAGES OF THE PLANNING OF THE STUDY THROUGHOUT THE STUDY PROCESSES AND IT MUST BE MEANINGFUL ALLOWING US TO DRAW CONCLUSIONS ABOUT THIS DIVERSE POPULATION AND IT REALLY REQUIRES THOUGHTFUL AND DELIBERATE APPROACHES TO MAKE SURE WE RECOGNIZE THAT MANY OLDER ADULTS LIVING WITH COMMON CONDITIONS AND SYNDROMES AND NOW I WILL TURN THINGS OVER TO OUR PANEL. >> SO FIRST OFF WE WILL HAVE DR. ADAMS-CAMPBELL PRESENT HER EXPERTISE ON THE RECRUITMENT CRITERIA. THANK YOU, DR. ADAM-CAMPBELL. >> THANK YOU. I WILL FOCUS ON INCLUSION OF MINORITIES AND ADDRESSING HEALTH DISPARITIES. I THINK THAT'S IMPORTANT AND NEED WHD YOU TALK ABOUT CLINICAL TRIALS. NEXT SLIDE, PLEASE. AS DR. PEREZ ESTABLISHED THIS ALREADY TALKED ABOUT IN HIS OPENING, SOCIAL DETERMINANTSS OF HEALTH ARE VERY IMPORTANT BECAUSE THEY PLAY A MAJOR ROLE IN THE HEALTH OUTCOMES WHETHER WE'RE THINK BEING THE HEALTH COVERAGE AND HEALTHCARE SYSTEM EDUCATION OR ECONOMIC STABILITY, AND AND CLINICAL TRIALS AND I THINK IT'S IMPORTANT THAT WE DO NOT EQUATE INDIVIDUALS IMPACTED BY THE SOCIAL DETERMINANTS OF HEALTH WITH LACK OF INTEREST AND I THINK THAT'S A BIG MISUNDERSTANDING THAT PEOPLE CAN BE INTERESTED IN CLINICAL TRIALS AND PEOPLE ARE INTERESTED WHEN THEY ARE INTERESTED WHEN THEY HAVE CANCER AND SURVIVING CANCER, THEY WOULD LOVE TO HAVE THE STATE-OF-THE-ART TREATMENT AND THESE ATTRIBUTES REALLY PLAY A ROLE THAT'S NEGATIVE TO THEIR SUCCESS. AND FROM THAT PERSPECT WE AT GEORGE TOWN HAVE ESTABLISHED A MEDICAL LEGAL PARTNERSHIP BECAUSE SOME THINGS THAT FOR TREATMENT AND YOU CAN'T LOSE YOUR JOB, AND LEGAL PLEA BECAUSE YOU'RE UNDERGOING TREATMENT AND THESE PARTNERSHIPS HELP US TO ENHANCE THE ABILITY OF RECRUITING AND ENGAGING PEOPLE IN THESE TRIALS BECAUSE PEOPLE ARE INTERESTED IN SAVING LIVES. ALSO TRANSPORTATION BECOMES IMPORTANT. AND MORE IMPORTANTLY IT'S CULTURAL LANGUAGE AND SENSITIVITY. ALL OF THESE THINGS BECOME MORE AND MORE IMPORTANT IN A FEW MINUTES BUT SOCIAL DETERMINANTS OF HEALTH ARE THE CORNERSTONE FOR WHY WE HAVE SO MANY HEALTH DISPARITIES AND PEOPLE NOT INTERESTED. NEXT SLIDE. AND GET THIS OPPORTUNITY TO DIG BACK INTO A PUBLICATION THAT I HAD JUST TRYING TO FOCUS ON WHY PEOPLE ARE EXCLUDED. AS YOU CAN SEE IN THIS STUDY, WE LOOKED AT CONSECUTIVE NUMBER OF AFRICAN AMERICANS COMING IN FOR CLINICAL TRIALS AND WE FOUND THAT 1 OF THE BIGGEST ISSUES THAT DROVE EVERYTHING--EVERYTHING WAS THE LACK OF AVAILABILITY OF [INDISCERNIBLE] BECAUSE OF THE EXCLUSION CRITERIA AND YOU CAN SEE HERE CO-MORBIDITIES ON MULTIPLE CANCERS ALL THE WAY DOWN TO SOMETHING DISEASE RELATED SUCH AS CM TEST OFTEN--DECISION ROAN AND THEY WANT TO HAVE GREATER THAN 15 NANO GRAMS DECILITER FOR TESTOSTERONE, AND I'M ONLY PICKING THAT THAT THAT THE INCLUSION MAY BE ARBITRARY, IF BLACK MEN HAVE A HIGHER LEVEL THAN WHITE MEN, WHY SHOULDN'T THEY COME. WHY COULDN'T IT BE A PERCENTAGE DROP, I THINK WE'VE BEEN USING COOKIE CUTTER CRITERIA FOR DECADES AND AS I PARTICIPATE IN THE COOPERATIVE TRIALS AND MEETINGS, I ASK HOW COME WE ALWAYS HAVE THE SAME EXCLUSION CRITERIA, WOULD WE EVER MOVE BEYOND THAT AND I CONTINUING TO DO THAT, WE NEED TO REALLY, REALLY THINK ABOUT NOT ONLY IS THE SCIENCE SO IMPORTANT BUT IT'S SO IMPORTANT TO HAVE THE PEOPLE ENGAGE--SO IMPORTANT TO HAVE THE PEOPLE ENGAGED AS WELL AND WE CAN HAVE THE PATIENTS PARTICIPATE--CAN'T HAVE THE PATIENTS PARTICIPATE IF THE SCIENCE DOESN'T INCORPORATE THE SCIENCE IN IT BECAUSE OF THE EXCLUDING CRITERIA. AND WE ALSO HAVE TO THINK ABOUT IMPLICIT BIAS. I'VE HEARD PHYSICIANS SAY, WELL, THEY DON'T DO IT, THEY'RE NOT INTERESTED AT ALL AND--THAT OBJECTSIVE IN OUR APPROACH IN TERMS OF TRYING TO REACH OUT TO INCLUDE MORE PEOPLE WHICH REQUIRES A LOT MORE EDUCATION FOR BOTH SIDES AND THE NEXT SLIDE, MY LAST LITTLE SLIDE, WE HAVE TO DISPEL MYTHS AND A LOT OF THESE MYTHS ARE BECOME OF IMPLICIT BIAS, A LOT OF THEM ARE BECAUSE OF THE SOCIAL DETERMINANTS OF HEALTH AND WE ALWAYS BLAME THE WRONG PERSON, IS THE VICTIM THE PATIENT OR SHOULD THE VICTIM NOT BELET PATIENT BUT JUST THE PROCESS, WE JUST HAVE TO CLEAN UP THE PROCESS AND MAKE SURE THAT OUR EXCLUSION CRITERIA ARE MORE ROBUST, NOW THE WHOLE ISSUE IS ABOUT ADVERSE EVENTS. WE WANT SAFETY IN OUR CLINICAL TRIALS, THAT IS KEY TO EVERYTHING BUT TO HAVE SAFETY, SOMETIMES WE MIGHT NEED TO LOOK VERY CLOSELY AT THE REPORTING OF ADVERSE EVENTS FOR PEOPLE WHO ARE INELIGIBLE BUT THEY'RE STILL GETTING CHEMO THERAPY, THEY'RE STILL BEING TREATED AND SEE, ARE WE HOLDING ON TO THESE EXCLUSION CRITERIA WHEN WE REALLY COULD TURN THEM LOOSE OR LOOSEN UP THE REQUIREMENTS SO THAT PEOPLE COULD BE INCLUDED. THERE ARE MANY PAPERS BEING WRITTEN ABOUT THE NEED FOR MORE ROBUSTNESS IN TERMS OF ELIGIBILITY CRITERIA BUT WE NEED TO FOCUS ON ACTUALLY LOOKING AT AND EXAMINING THE ADVERSE EVENTS THAT'S HAPPENING IN THOSE COMMUNITIES IN THOSE INDIVIDUALS TO SEE IF WE REALLY HAVE IT RIGHT BECAUSE 40 OR 50 YEARS AGO THOSE CRITERIA MIGHT NOT BE THE SAME OR RELEVANT. AND EVEN IF HAVE YOU CANCER REGARDLESS OF EVERYTHING ELSE, THEY WILL HAVE TO BE TREATED TO HAVE ANY CHANCE TO SURVIVE IN MOST CASES. CULTURAL SENSITIVITY IS ALSO REALLY IMPORTANT, VERY CRITICAL TO THE PICTURE AND I THINK THAT WE HAVE TO DEVELOP TEAMS AND WORK WITH TEAMS OF PEOPLE. DOESN'T MEAN THE ENTIRE TEAM HAS TO BE MINORITY OR HISPANIC OR BLACK OR WHATEVER, BUT WE NEED TO HAVE IA TEAM THAT CAN RELATE--SOMEBODY CAN RELATE TO THE PARTICIPANT THAT CAN TALK TO THE PARTICIPANT AND GET THE RIGHT MESSAGE OUT AND MAKE SURE THEY UNDERSTAND BECAUSE LINGUISTICS ARE SO IMPORTANT AS WELL. YOU CAN'T REALLY TRANSLATE IT OR UNDERSTAND IT IN A PERSON'S NATIVE TONGUE SOMETIMES THAT WILL DISTRACT AND KEEP PEOPLE FROM PARTICIPATING. BUT WE HAVE TO ENHANCE THE PATIENT PROVIDER COMMUNICATION AND EDUCATION SKILLS. WE HAVE TO MAKE CERTAIN THAT OUR PROVIDERS ARE ABLE TO REALLY TALK TO THE PATIENT AND THAT OUR COMMUNICATION IS SUCH THAT THE PATIENT REALLY UNDERSTANDS AND THAT TAKES I THINK A GREAT AMOUNT OF WORK. AND THE LAST ITEM I MENTIONED WAS INCREASES IN DIVERSITY AMONG PIs AND STAFF, PARTICULARLY AMONG PIs BECAUSE WE NEED TO MIX IT AND WE HAVE MORE INPUT AND INSIGHT INTO SOME OF THESE EXCLUSION CRITERIA, AS WELL AS AND MINORITIES AND UNDERREPRESENTED INDIVIDUALS ARE ALSO AT THE HELM AND INVOLVED AND ENGAGED IN THESE STUDIES BECAUSE OTHERWISE IT'S ALWAYS PITTING 1 PERSON AGAINST ANOTHER, 1 TEAM AGAINST ANOTHER AND I'VE ALSO HEARD THAT WELL, WE DON'T--IT'S NOT IMPORTANT THAT WE HAVE MORE MINORITIES, WE JUST NEED TO GET THE STUDY DONE. I THINK AS WE--AS OUR DEMOGRAPHICS CHANGE OVERTIME, IT WILL BE MORE IMPORTANT THAT WE HAVE EVERYBODY INCLUDED IN THESE STUDIES. THANK YOU. >> THANK YOU DR. ADAMS-CAMPBELL. NEXT WE HAVE DR. SAADE WHO WILL PEEK TO US ON CONSIDERATIONS IN ENROLLING PREGNANT WOMEN IN CLINICAL TRIALS. >> THANK YOU SO MUCH REALLY GRATEFUL FOR THE ORGANIZER OF THE WORKSHOP FOR INCLUDING PREGNANT WOMEN AND LET ME SAY THAT WHEN I SAY PREGNANT WOMEN, I ALSO MEAN POSTPARTUM AND LACTATING WOMEN BUT IT'S EASIER TO SAY, PREGNANCY OR WEGINANT WOMEN, 1 WORD. NEXT SLIDE. s I CAN REALLY TAKE DR. BOURGEOIS, AND REPLACE CHILDREN WITH PREGNANCY AND IT WILL APPLY THE SAME WAY, ALTHOUGH I DO SEE THAT PREGNANCY MIGHT BE SLIGHTLY LAGGING BEHIND WHAT'S DONE IN PEDIATRICS AND INCLUSION OF CHILDREN AND RESEARCH. WHY DO WE NEED TO INCLUDE PREGNANT WOMEN. WELL, JUST SHEER NUMBERS. WE HAVE 4 MILLION PREGNANCIES IN THE U.S. PER YEAR AND A HUNDRED MILLION WORLD WIDE AND EVEN IF WE DON'T TAKE INTO ACCOUNT MULTIPLE PREGNANCIES, TWINS AND TRIPLETS, THAT'S 8 MILLION INDIVIDUALS EVERY YEAR THAT ARE AFFECTED BY WHAT WE DO IN PREGNANCY. ALSO, THE OUTCOMES OF PREGNANCY HAVE BEEN GETTING WORSE AND WORSE FOR A VARIETY OF REASONS COMPLICATED PREGNANCIES ARE ON THE RISE AND MATERNAL MORBIDITY AND MORTALITY IS INCREASING AND THIS IS OCCURRING DURING A PERIOD OF TIME ON WHICH WE HAVE LIMITED EVIDENCE ON WHICH TO BASE TREATMENTS AND INTERVENTIONS BECAUSE WE DON'T INCLUDE PREGNANT WOMEN IN TRIALS OF GENERAL TRIALS OF ABOUT INTERVENTIONS----REALLY NEED IT BECAUSE WE NEED TO UNDERSTAND HOW TO TREAT THESE PATIENTS AND WE CANNOT EXTRAPOLATE THE FINDINGS IN NONINDIVIDUALS TO PREGNANCY BECAUSE THERE ARE PHYSIOLOGIC CHANGES IN PREGNANCY THAT AFFECT FARM CO KINEETICS, PHARMA CO DYNAMICS AS WELL AS OTHER INTERVENTIONS AND THESE OCCUR THROUGHOUT PREGNANCY SO WHAT HAPPENS THE CHANGES IN EARLY PREGNANCY MAY NOT BE THE SAME AS LATER IN PREGINANCE WHICH MAKES IT SLIDELY MORE COMPLEX. NEXT SLIDE, PLEASE. SO WHAT HAPPENS IS IN GENERAL IN PREGNANCIES THAT WE OVEREMPHASIZE THE RISK TO THE FETUS AND UNDEREMPHASIZE THE RISK OF LACK OF EVIDENCE. SO THE OPTIONS FOR PREGNANT WOMEN ARE TO TAKE A MEDICATION WITH UNKNOWN SAFETY EFFICACY OR NOT TO TAKE THAT MEDICATION. THESE ARE NOT GOOD OPTIONS. SO IN FACT, RELUCTANCE TO INCLUDE PREGNANT WOMEN IN CLINICAL TRIALS BECAUSE OF FETAL CONCERN PARADOXICALLY INCREASES FETUS RISKS FROM USE OF DRUGS IN CLINICAL PRACTICES AND THAT'S WHAT I MEAN BY UNDEREMPHASIZING THE RISK OF LACK OF EVIDENCE. WE DON'T TALK ABOUT THAT, WE ONLY TALK ABOUT WHAT'S THE RISK TO THE FETUS. THE OTHER ISSUE THAT LIMITS INCLUSION IS A PATERNALISTIC ATTITUDE OR WHAT USED TO BE CALLED VULNERABILITY OF PREGNANT WOMEN. NOW FORTUNATELY, THANKFULLY THAT TERM WAS REMOVE ED FROM THE MORE RERECENT DESIGNATION FROM THE COMMON RULES BUT WHILE IT WAS REMOVE FRIDAY THE TEXT, IT'S STILL THERE IN THE MINDS OF PEOPLE AND RESEARCHERS AND REGULATORS. THE NEXT ISSUE IS REGULATORY BURDEN, PARTICULARLY WHEN RESEARCHERS NEED TO OBTAIN AN I& D FROM THE FDA, THERE'S ALWAYS THIS LIMIT OR THIS HURDLE, OF PROVIDING ENOUGH EVIDENCE THAT IT IS SAFE IN PREGNANCY. IRBs ALSO HAVE LIMITED EXPERTISE AS WAS SAID BEFORE ABOUT CHILDREN MOST OF IRB MEMBERS DO NOT REALLY UNDERSTAND PREGNANCY VERY WELL OR OVEREMPHASIZE THE RISK OF THE FETUS AS I SAID BEFORE. ONE PARTICULAR ISSUE TO PREGNANCY THAT'S SLIGHTLY DIFFERENT THAN WHAT WAS SAID ABOUT CHILDREN IS THAT THERE SHOULD BE SO MORE THAN A MINIMAL RISK IN ORDER TO APPROVE AN INTERVENTION OR RESEARCH OR INCLUSION OF PREGNANT WOMEN BUT WHAT IS MINIMAL RISK. WE HAVE TO REMEMBER THAT EVERY PREGNANCY HAS SOME RISK PARTICULARLY HETEROGENEOUS O GENIC RISK, 3 TO 4 BABIES ARE BORN WITH CONGENITAL ANOMALIES SO HOW MUCH OF THAT IS MINIMAL RISK, HOW WE WE DETERMINE MINNAL RISK OR HOW DO WE GET THAT. THE PROBLEM IS THERE IS NO GOOD CLINICAL RESEARCH MODEL. THERE ARE NO GOOD ANIMAL MODELS AT PARTICULARLY AND PARTICULARLY PREGNANCY COMPLIKAITIONZS-COMPLICATIONS PARTICULARLY WHEN IT COMES TO TRANSPLACENTA TRANSFER. ALSO MOST PRECLINICAL HUMAN MODELS ARE HOST HOC OR AFTER THE DLRY SO IT'S HARD TO FOLLOW THE PREGNANCY LONGITUDINALLY, NOT INVASIVELY IN ORDER TO OBTAIN THESE MINIMAL RISK OR ASSESSING THE RISK OF ANY INTERVENTION OR ANY TREATMENT. ONE THING THAT'S DIFFERENT THAN WHAT DR. BOURGEOS MENTIONED IS WE DON'T HAVE THE LUXURY IN PREGNANCY OF HAVING A WAY OUT IF THERE IS AN OPTION FOR GENERALIZABLE KNOWLEDGE. WHILE THIS IS OKAY FOR RESEARCH IN CHILDREN, IT'S NOT INCLUDED AS FAR AS RESEARCH IN PREGNANCY AND THAT COULD BE SOMETHING FOR THE FUTURE TO INCLUDE AN APPROVAL OF INCLUSION OF PREGNANT WOMAN. FINALLY, AS YOU MAY KNOW A LOT OF RESEARCH THAT IS DONE PHASE 3 CLINICAL TRIALS ARE REALLY SUPPORTED BY INDUSTRY. WHAT NIH DOES IS MOSTLY THE DISCOVERY, THE PRECLINICAL OR THE TRANSLATIONAL RESEARCH THAT'S FUNDED BY NIH. AND THEN INDUSTRY COMES AND SPENDS THE HUNDREDS OF MILLIONS OF DOLLARS, GETS THE FDA APPROVAL IN ORDER TO IMPLEMENT TREATMENT, PROMISING TREATMENT INTO CLINICAL PRACTICE. AND THAT PROBLEM IS--THIS A PROBLEM IN PREGNANCY BECAUSE OF THE LUKE WARM INTEREST FROM INDUSTRY. NEXT SLIDE. SO WEED NEED TO INCENTIVIZE RESEARCHERS. WE NEED TO INCENTIVIZE RESEARCH IN PREGNANCY. AND WHILE I THINK NICHD AND OTHER NIH INSTITUTES HAVE AN INCENTIVE TO DO RESEARCH IN PREGNANCY AS DR. BIANCI HAS MENTIONED NICHD--I THINK WHERE WE NEED TO INCENTIVIZE AS AN INDUSTRY AND AS DR. BBUSINESS OURGEOIS SAID THERE IS AN ECONOMIC DISADVANTAGE IN PREGNANCY BECAUSE THE RETURN ON THE INVESTMENT IS NOT THERE, SO WE NEED TO INCENTIVIZE INDUSTRY WITH OTHER REGULATIONS LIKE THE BPCA, THERE IS ALSO LITIGATION% DISINCENTIVE FOR INDUSTRY THAT WE NEED TO ADDRESS. OTHER WAYS TO IMPROVE RESEARCH IN PREGNANCY AND IMPROVE INCLUSIO IN PREGNANCY IS TO IMPROVE THE COMPOSITION OF THE IRB BUT MORE IMPORTANTLY, USE CENTRALIZED IRBTHAT IS UNDERSTAND RESEARCH AND PREGNANCY. ALSO WE NEED MORE MEASURED REGULATION AND EXAMPLE OF WHICH I SAID BEFORE IS TO CHANGE--ADD IN ARK DITION TO MINIMUM RISK ADD THAT IT'S POSSIBLE TO DO RESEARCH IF THERE IS GENERALIZABLE BENEFIT TO THE POPULATION IN GENERAL AND ALSO BY DECREASING THE BURDEN OF RESEARCH AND PREGNANCY WE CAN DO MORE RESEARCH THAT IS MORE COST EFFECTIVE THAT ALLOWS EASIER INCLUSION OF PREGNANT WOMEN DURING ACTUAL MEDICAL CARE OR CLINICAL CARE AND THESE ARE EXAMPLES OF THESE ARE COMPARATIVE EFFECTIVENESS RESEARCH WHERE WE'RE COMPARING 2 ACCEPTABLE TREATMENTS OR GROUP RANDOMIZATION TRIAL, CLUSTER RANDOMIZATION TRIAL WHERE WE CAN TEST DIFFERENT INTERVENTIONS, CLINICALLY ACCEPTABLE INTERVENTIONS IN DIFFERENT CLUSTERS ALL THROUGH TIME. AND FINALLY, WE CAN REFRAME THE RISK AND BENEFIT. INSTEAD OF FOCUSING ON THE RISKS, WE SHOULD FOCUS ON THE BENEFIT OF RESEARCH AND PREGNANCY. WE NEED TO BALANCE THE RISK OF INCLUSION VERSUS THE RISK OF EXCLUSION AND WE NEED TO HAVE REALISTIC EXPECTATIONS OF ASSESSING THE RISK OF INCLUSION, IF WE DON'T HAVE A GOOD PRECLINICAL MODEL BUT REQUIRE SAFETY DATA BEFORE INCLUSION OF PREGNANCY, THAT'S A [INDISCERNIBLE] OR NOT, THIS IS A CYCLE WE CANNOT BREAK. IT'S NOT ONLY ACCEPTABLE TO INCLUDE PREGNANT WOMEN IN RESEARCH AND CLINICAL TRIALS, IT'S ACTUALLY IMPERATIVE OTHERWISE WE'RE NOT GOING TO IMPROVE PREGNANCY OUTCOMES. THANK YOU. >> NOW WE WILL TURN TO DR. CELIA FISHER. DR. FISHER? >> SORRY. THANK YOU. THANK YOU FOR ORGANIZING THESE IMPORTANT PANELS AND I WILL BE SPEAKING ON INCLUSION OF SEXUAL MINORITY YOUTH IN RESEARCH. CAN WE GO TO THE NEXT SLIDE. SEXUAL MINORITY ADOLESCENT MALES ACCOUNT FOR 81% OF HIV INFECTIONS, STATE MATURE MINOR LAWS PERMIT YOUTH UNDER 18 INDEPENDENT ACCESS TO HIV SERVICES AND ON THE OTHER HAND OHRP AND FDA REGULATIONS FOR RESEARCH, MATURE MINORS ARE CONSIDERED ADULTS. HOWEVER, IRBs HAVE BEEN RELUCTANT TO WAVE GUARDIAN PERMISSION FOR MATURE MINORS BASE INDEED PART ON CONCERNS REGARDING YOUTH CAPACITY TO SELF-CONSENT. THIS HAS BECOME A CRITICAL BARRIER TO HIV RESEARCH RECRUITMENT AMSM HAVE REFUSED PARTICIPATION DUE TO FEARS GUARDIAN PERMISSION WILL OUT THEM LEADING TO FAMILY REJECTION, THIS HAS RESULT INDEED UNDERPOWERED STUDIES AND NONREPRESENTATIVE SAMPLES OF ONLY THOSE YOUTHS WITH SUPPORTIVE FAMILY RELATIONSHIPS. NONETHELESS, IN 2018, THE FDA APPROVED PREP FOR ADOLESCENCE A DAILY PILL FOUND EFFECTIVE FOR REDUCING HIV ACQUISITION IN ADULTS. THIS IS TROUBLESOME SINCE MEDICATIONS FOR ADOLESCENTS BASED ON EXTRAPOLATIONS OF DATA FROM ADULT STUDIES DO NOT SUFFICIENTLY ADDRESS DEVELOPMENTAL CHALLENGES FOR MEDICATION UPTAKE AND ADHERENCE IN THIS AGE GROUP. ADHERENCE PROBLEMS WITH PREP PILL VS LED TO CURRENT RCTs WITH ADULT MSM COMPARING ADVOCACY AND SAFETY OF ORAL PREP TO A LONGER LASTING INJECTABLE FORM. ONCE APPROVED, THESE TRIALS WILL BE CONDUCTED WITH AMSM, UNDERSCORING THE URIGENCE EVALUATION PROCESS DATA ON MATURE MINORS CAPACITY TO CONSENT TO INSURE THESE STUDIES INCLUDE ADEQUATE SAMPLES. SLIDE 2, PLEASE. TO INFORM THESE TRIALS, WE ASSESS CONSENT CAPACITY FOR AN ORAL VERSUS INJECTABLE PREP RCT COMPARING 14 AND 17 YEAR-OLDS TO OLDER MSM WHOSE LEGAL RIGHT TO SELF-CONSENT IS UNCHALLENGED. PARTICIPANTS VIEW THE VIDEO AND A CONSENT FORM FOLLOW BY OPEN ENDED AND YES NO ITEMS. --PARTICIPATION BASED ON GUARDIAN PERMISSION REQUIREMENTS. ACROSS AGE THE MAJORITY DEMONSTRATED PROCEDURES, SIDE EFFECTS, RANDOM ISIGNMENT, PROTECTIONS AND REASONING INDICATED THEY WERE UNLIKELY TO CONSENT IF THEY ANTICIPATED NEGATIVE CONSEQUENCES. HOWEVER, REGARDLESS OF AGE, SOME INDICATED ONLY PARTIAL BED UNDERSTANDING OF INCLUSION CRITERIA, PRERANDOMMIZATION SAFETY TESTING STUDY PURPOSE AND DID NOT INCLUDE COMPARISON OF RISKS AND BENEFITS IN THEIR PARTICIPATION FOR REASONING. NEXT SLIDE. IN CONCLUSION, PERMITTING SELF-CONSENT OF MATURE MINORS IS ESSENTIAL IF WE ARE TO REDUCE BARRIERS TO RECRUITMENT AND ADEQUATELY POWER HIV TRIALS INVOLVING AMSM. THIS IS ALSO TRUE FOR ADEQUATE SAMPLING OF OTHER ADOLESCENT POPULATIONS IN HEALTH RESEARCH. FIRST WHAT WE NEED IS TO ENCOURAGE THE FDA AND OHRP TO THEMSELVES ENCOURAGE IRBs TO ATTEND TO DEFINITIONS OF MATURE MINORS AS ADULTS IN FEDERAL REGULATIONS. IN ADDITION ACROSS STUDIES WE NEED TO INCREASE SAMPLE REPRESENTATIVENESS BY REQUIRING ADDITIONAL DATA ON MATURE MINORS CONSENT CAPACITY. THIS CAN ADDRESS IRB CONCERNS, INFORM PROCEDURES THAT WILL REDUCE CONSENT OF VULNERABILITIES AND PROVIDE GUIDANCE FROM MEETDING NEW COMMON RULE REQUIREMENTS FOR IDENTIFYING KEY CONSENT INFORMATION AND WHETHER ADOLESCENTS CAN BE CONSIDERED REASONABLE PERSONS WITH THE RIGHT TO INDEPENDENTLY CONSENT TO RESEARCH. THANK YOU. >> THANK YOU AND DR. DALE. >> THANK YOU VERY HAVING ME HERE AND I'M IMPRESSED BY THE DNCHS ACROSS THE GROUPS AND WILL EMPHASIZE THIS FOR THE OLDER ADULTS WHO DO HAVE CANCER ALONG WITH A NUMBER OF OTHER CONDITIONS. I JUST WANT TO SAY MY SPECIAL THAIRNGS TO MARIE BERNARD WHO THROUGH THE YEARS HAS BEEN SUCH AN ADVOCATE FOR THIS AND ADVOCATING FOR OLDER ADULTS IN RESEARCH OF ALL KINDS. NEXT SLIDE. THE FIRST POINT IS THAT THE MAJORITY OF PATIENTS WITH CANCER ARE OVER THE AGE OF 65. THIS IS NOT A GROUP OF PATIENT WHO IS ARE IN THE MINORITY, IN FACT, YOUR TYPICAL CANCER PATIENT WILL BE OVER THE AGE OF 65, AND IN MANY WAYS ARE THE TYPICAL CANCER PATIENT WHICH MAKES IT ESPECIALLY IRONIC THAT THEIRA LESS REPRESENTED--THEIR LESS REPRESENTED IN MOST OF THE TRIALS TO GIED OUR THERAPIES FOR CANCER CARE. NEXT SLIDE, PLEASE. I'M SORRY NEXT 1 IS 1 MORE. SO THIS SLIDE IS SUGGEST THAT THERE HAS BEEN IN PLACE A NUMBER NUMBER OF PEOPLE OVER A CERTAIN AGE AND CHANGE THE DISTRIBUTION TO BETTER REFLECT THE POPULATION. IF YOU DO LOOK AT NCI COOPERATIVE GROUP TRIALS WHICH IS 1 REPRESENTATIVE TYPE OF TRIAL, BOTH IN PHASE 2 AND PHASE 32 STUDIES WHICH ARE WHAT ESTABLISHED THE STANDARD FOR USE OF THERAPEUTICS IN CANCER TRIALS. YOU COULD ADD THE NEXT 2 CLICKS, PLEASE. YOU CAN SEE THAT SINCE 2001 UP THROUGH 2011 AND THIS IS CHANGING MINIMALLY AS WE MOVE FORWARD, WE'RE STILL CONTINUING TO HAVE THE SAME AGE DISTRIBUTION OVER ALL OF THIS TIME. THERE HAVE BEEN SOME CHANGES AS WE'VE CHANGED THE ENROLLMENT CRITERIA BUT IT STILL DOESN'T REFLECT THE POPULATION, ANOTHER POINT TO MAKE HERE IS THAT THOSE OLDER ADULTS WHO ARE INCLUDED IN CLINICAL TRIALS, THOSE OVER 65 AND THOSE OVER 75 ARE THE ALL STARS OF OLDER ADULTS. THEY ARE HEALTHIER, WITH LESS CO MORBIDITIES AND LESS OTHER CONDITIONS OF THE TYPE DR. BOYD THE TRIAL. SO EVEN WHEN WE COMPLETE THE TRIALS AND LEARN WHAT WE ARE ABLE TO FROM OLDER ADULTS, THEY'RE SURPRISINGLY SIMILAR TO THE YOUNGER ADULTS EMPHASIZING IT'S LESS ABOUT AGE AND MORE ABOUT THE OTHER THINGS THAT OLDER ADULTS HAPPEN TO HAVE CO-ASSOCIATE WIDE THEIR CONDITIONS--CO-ASSOCIATED WITH THEIR CONDITIONS AND FUNCTIONAL IMPARENTS THEY MAY HAVE, COGNITIVE IMPAIRMENTS THEY MAY HAVE AND THOSE PATIENTS ARE SIMPLY NOT INCLUDED IN THE TRIALS. THISSED WELLS TO THE BOTTOM LINE WHICH I WILL EMPHASIZE AT THE END, THIS IS MORE ABOUT US THAN IT IS ABOUT THE PATIENTS. IT'S ABOUT OUR FAILING TO DESIGN TRIALS AND CREATE TRIALS AND CREATE RESEARCH IN GENERAL THAT ALLOWS FOR THE ENROLLMENT THAT VULNERABLE PATIENTS OF ALL KINDS INCLUDING OLDER ADULTS WITH DIFFERENT VARIETIES OF FRAILTY AND VULNERABILITIES. --THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY TO EMPHASIZE THE APPROPRIATE USE OF EVALUATIONS FOR OLDER VULNERABILITY PATIENTS. THIS LED TO THE CURRENT ASCO GUIDELINES ON THE USE OF GERIATRIC ASSESSMENTS IN THE ASSESSMENT MANAGEMENT OF OLDER ADULTS WITH CANCER. THERE WERE 4 PRIMARY POINTS THAT ARE MADE WITHIN THAT DOCUMENT WHICH I ENCOURAGE PEOPLE TO LOOK AT. ONE THAT GERIATRIC ASSESSMENTS HAVE SUFFICIENT EVIDENT FROM A NUMBER OF PEOPLE TO BE USED FOR ANY AND ALL PATIENTS, BOTH IN PRACTICE AND IN TRIALS TO IDENTIFY THOSE VULNERABILITIES. INCOME 2 THAT YOU HAVE TO INCLUDE THE ESSENTIAL GERIATRIC ASSESSMENT DOMAINS IN ALL OF THEIR AREAS THAT THEY'RE MOST IMPORTANT. THIS INCLUDES FUNCTIONAL LOSSES, COGNITIVE IMPAIRMENTS, SOCIAL LOSSES, EMOTIONAL CONCERNS, FALLS, AMONG THE DOMAINS. MISSING IN THESE DOMAINS WE FAIL TO IDENTIFY IN OUR DATABASES THOSE ELEMENTS THAT ARE MOST IMPORTANTLY ASSOCIATED WITH OUTCOMES ENCLOUDING HOSPITALIZATIONS, CHEMO THERAPY, TOXICITIES AND EVEN DEATH. IN ADDITION, WHETHER A PATIENT IS ENROLL INDEED A TRIAL, IT'S IMPORTANT TO CONDUCT PROGNOSTICATION WHICH IS REMAINING LIFE EXPECTANCY PROGNOSTICATION INDEPENDENT OF THEIR CANCER DIAGNOSIS FOR WHICH WE OFTEN HAVE PRECISE INFORMATION ABOUT PROGNOSTICS. BUT FOR ALL OF THE OTHER CONDITIONS AND THE COMPETING RIIVES THAT PATIENTS HAVE, WE RUN THE RISK IN OVERLY TREATING CANCER IN VULNERABLE PATIENTS OF EXACERBATING JUST THOSE OTHER CONDITIONS THAT WOULD LOWER THEIR PROGNOSTICATION AND IRONICALLY SHORTEN THE LIVES OF PATIENTS FOR WHOM WE'RE HYPER FOCUSED ON THEIR DIAGNOSIS WHETHER CANCER OR OTHER 1 AND THE FOURTH POINT IS TO ENACT A GERIATRIC ASSESSMENT GUIDED TARGET INTERVENTION. THIS YEAR AT ASCO, THERE WERE 4 SEPARATE RANDOMIZED CONTROL TRIALS THAT SHOWED THAT SUCH INTERVENTION CANS LEAD TO A SUBSTANTIAL DECREASE IN CHEMO THERAPY TOXICITY, HOSPITALIZEITIONS, INCREASES IN QUALITY OF LIFE AND THOSE STUDIES WILL BA APPEARING IN PRINT PROBABLY IN THE NEXT 6-9 MONTHS. AND FINALLY, I WILL END WITH PERCEIVED BARRIERS TO THE UCGA COME UP AS IF THEY'RE TOO DIFFICULT TO INCLUDE IN RESEARCH STUDIES AND EVEN CLINICAL PRACTICE AND THE TRUTH IS THAT A NUMBER OF STUDY VS SHOWN THAT THEY ARE NO MORE DIFFICULT TO DO THAN A NUMBER OF OTHER THINGS THAT WE DO INCLUDING IMAGING STUDIES, BIOPSIES OF VARIOUS KINDS, LESS TIME INTENSIVE AND MOSTLY CAN BE DONE WITHOUT A PROVIDER OR PHYSICIAN OR EVEN UPON A NURSE PRACTITIONER BUT CAN BE DONE BY STAFF TO PROVIDE THE ESSENTIAL INFORMATION NECESSARY TO MAKE DECISIONS THAT ARE IMPORTANT. AND WITH THAT I WILL END MY REMARKS. >> THANK YOU SO MUCH. WE ARE DELIGHTED TO NOW SHIFT OUR FOCUS TO THE PANEL PORTION OF THIS SECTION AND TAKE AS MANY QUESTIONS AS POSSIBLE. SO TRY TO ASK OUR PANELISTS TO KEEP THEIR RESPONSES BRIEF. WE WILL ALSO WELCOME YOUR COMMENTS AND QUESTIONS IN THE CHAT BOX. DR. BOURIMRKS EOIS, YOU WANT TO ASK THE FIRST QUESTION PLEASE. >> THANK YOU. FIRST QUESTION I WOULD LOAMACYIC TO ASK DR. SAADE TO SPEAK TO WHAT HE THINKS BRIEFLY 1 OR 2 SOLUTIONS THAT MIGHT INCREASE ENROLLMENT OF PREGNANT WOMEN IN CLINICAL TRIALS. >> THANK YOU, I WANT TO GIVE A SHOUT OUT TO THE [INDISCERNIBLE] REPORT THAT DR. DALE MENTIONED BECAUSE IT'S MORE IMPORTANT THAN ANYTHING I WILL SAY RIGHT NOW. I WILL HEIGHT LIGHT A COUPLE THINGS THAT I THINK COULD GET US START INDEED THE SHORT-TERM. FIRST I MENTIONED THE IRB AND THE EXPERTISEOT IRB AND I THINK THAT CENTRALIZING IRB RESEARCH IN PREGNANCY WILL BE VERY USEFUL. NIH IS ALREADY MOVING TOWARDS THAT, I THINK I MENTIONED ALSO ADDING TO THE COMMON RULE, ALLOWING RESEARCH IN PREGNANCY IF THERE IS GENERALIZABLE KNOWLEDGE THAT'S GOING TO BE BENEFITING FROM THIS KNOWLEDGE. I DON'T SEE WHY IT'S IN CHILDREN BUT IT'S NOT IN PREGNANCY, I THINK IT SHOULD BETTER WHATEVER IS IN CHILDREN AND THEN I WOULD SAY LONG-TERM, I THINK WE NEED TO SUPPORT AND PROMOTE AND DEVELOPING MORE RESEARCH TO DETERMINE RISKS IN PREGNANCY. WE DON'T HAVE GOOD METHODS RIGHT NOW. WE DON'T HAVE GOOD PRECLINICAL MODELS. DEVELOP THESE MODELS. THAT WILL REQUIRE INVESTMENT AT NIH OR OUTSIDE NIH, THERE IS ALREADY A START THERE LIKE THE HUMAN PLACENTA PROJECT THAT WILL LEAD US SOMEWHERE BUT WE NEED MORE OF THESE. >> --UNDERREPRESENTED PERSONS CAN BAR TIS PARTICIPATE IN A TRIAL IN CLINICAL TRIALS. >> I THINK THE BEST WAY WE HAVE DONE IT HAS BEEN USING PATIENT NAVIGATORS AND BY HAVING PATIENT NAVIGATION WE'RE ABLE TO ADDRESS MANY OF THESE ISSUES BECAUSE THEY DO A LOT OF THE LEG WORK TO HELP IDENTIFY THE PROBLEMS AND ALSO FIND THE RESOURCES AND UTILIZE THE RESOURCES THAT CAN ADDRESS THE PROBLEMS AND THAT HAS BEEN VERY HELPFUL AND RIGHT NOW WE'RE USING IT FOR RECRUITING FOR CLINICAL TRIALS AND BECAUSE OF THE PATIENT NAVIGATION WHO WILL KNOW WHO NEEDS WHAT AND WHEN THEY NEED IT, WE CAN ADDRESS THOSE ISSUES AND ENROLL THEM AND FOLLOW THEM AND TRACK THEM AND MAKE SHRN THEY ARE ATTENTIVE TO THE REQUIREMENTS OF THE CLINICAL TRIALS. >> THANK YOU FOR THAT. OUR NEXT QUESTION IS FOR DR. FISHER, CAN YOU SAY WHETHER ENROLLING ADOLESCENTS INTO CLINICAL TRIALS SHOULD CLINICAL COMPETENCE TO CONSENT BE ASSESSED IF GUARDIANS REFUSE OR IF GUARDIANS DO NOT PROVIDE PERMISSION FOR ENROLLMENT? >> WELL, I THINK THE ISSUE HERE BECOMES 1 OF EQUITY AND SINCE WE DO NOT ASSESS NORMATIVE HEALTHY ADULTS OR 18-19 YEAR-OLDS WHO ARE CONSIDERED LEGAL ADULTS, THEN THERE'S REALLY AN ISSUE REGARDING WHETHER OR NOT WE ASSESS THE COMPETENCE TOW CONSENT AND THE OTHER PROBLEM IS WHAT IS THE CRITERIA FOR CONSENT. ARE WE GOING TO ALSO COMPARE THEIR CONSENT TO THAT OF ADULT WHO IS AREN'T EVEN IN THAT PARTICULAR STUDY. SO IT'S A SIGNIFICANT PROBLEM. ONE THING WE CAN DO IS TO HAVE PARTICIPANT CONSENT ADVOCATES WHO IF AN INDIVIDUAL CHILD OR AN IRB THINKS THE CHILD MIGHT NEED SOME KIND OF ASSISTANCE THEN THAT PERSON CAN BE AVAILABLE. BUT MOST IMPORTANT I THINK, IS THAT NIH IN CONNECTION WITH FDA AND ORHP, REALLY HAVE TO BEGIN TO DISCUSS WITH IRBs AND PERHAPS PUT SOME GREATER PRESSURE ON THEM TO FOLLOW WHAT THE REGULATIONS SAY ABOUT DEFINING MATURE MINORS AS ADULTS. >> THANK YOU DR. FISHER. WE HAVE A QUESTION FOR DR. DALE AS WELL. >> ARE THERE VALIDATED TOOLS FOR GERIATRIC ASSESSMENT THAT ARE AVAILABLE FOR USE IN CANCER CLINICAL TRIALS? >> YEAH, THANK YOU. THERE ARE A NUMBER OF TOOLS THAT CAN BE USED AS A PACKAGE TO GIVE A FULL COMPREHENSIVE GERIATRIC ASSESSMENT THAT ARE VALIDATED AND PUBLISHED AND ARE IN THE GUIDELINES THAT I POINTED OUT EARLIER. ONE ADDITION I WOULD SAY TO THAT IS WHEN YOU CONSIDER USING THE GERIATRIC ASSESSMENT, THE INFORMATION IT PROVIDES IS QUITE EXTENSIVE BECAUSE IT TELLS YOU WHAT AREAS TO TARGET WHEN YOU ARE DOING A TRIAL, IT CAN DO PROGNOSTICATION AS WE MENTIONED EARLIER AND IT CAN ALSO GIVE YOU INFORMATION ABOUT THE OTHER CONDITIONS TO TARGET WHEN YOU'RE PROVIDING COMPREHENSIVE CARE, SO YOU GET A LOT OF OF BENEFITS FOR THE SMALL AMOUNT OF TIME IT TAKES TO ACTUALLY INCLUDE THEM IN A TRIAL. AND I WOULD ALSO EMPHASIZE, THEY HAVE TO BE THOUGHT OF UPFRONT, TOO OFTEN WE GET ASKED AND I'M SURE MY FELLOW PANELISTS WHO SAY CAN YOU STICK ON THESE EXTRA MEASURES AFTER THE TRIAL'S BEEN DESIGNED. IT'S IMPORTANT THE TRIALS BE DESIGNED UP FRONT WITH THE INCORPORATION OF THESE TOOLS. >> THANKS WILLIAM. I WILL TURN IT OVER TO THE NIH TO ASK A COUPLE MORE QUESTIONS. >> HI, THIS IS JIM GRIFFIN FROM NICHD, 1 OF THE CO-CHAIRS I ACTUALLY HAVE A QUESTION TO YOU FROM THE VIDEOCAST FEEDBACK BOX WHICH WE'RE MONITORING FOR QUESTIONS FOR THE PANELISTS AND THE QUESTION IS BEFORE CLINICAL TRIAL PLANNING, EARLY PHASE DEVELOPMENT OF DRUGS AND DEVICES SHOULD ENCOURAGE INVESTIGATORS TO CONSIDER CHILD HEALTH NEEDS. HOW CAN CHILD HEALTH INVESTIGATORS PROMOTE THIS IN THE EARLY DEVELOPMENT WITH THE GOAL OF LATER INCLUSION OF CHILDREN IN EXPERIMENTAL STUDIES? >> DR. BOURGEOIS OR DR. FISHER PERHAPS YOU WOULD LIKE TO TAKE THAT. >> SO AS I UNDERSTAND THE QUESTION IS WHETHER OR NOT THERE SHOULD BE PRELIMINARY STUDIES ON CHILD HEALTH NEEDS IN ORDER TO GUIDE WHAT THE INCLUSION AND/OR--POTENTIAL EXCLUSION CRITERIA SHOULD BE AND I AGREE WITH THAT WHOLE HEARTEDLY. I THINK THAT WE'RE NOT DOING ENOUGH IN TERMS OF PILOTING AND PRELIMINARY STUDIES BOTH ON--GOING TO CONSIDER THE VALUE OF OF THE CLINICAL TRIAL. , CAN I ALSO ADD THAT IT SHOULD BE CHILDREN AND PREGNANT WOMEN? >> AND I WOULD ALSO SAY IMPORTANTLY STUDIES HAVE SHOWN THAT CLINICAL RESEARCH IS OFTEN NOT WELL ALINE LIENED WITH THESE NEEDS IN POODIATRIC POPULATIONS AND MY GUESS IN OTHERS AS WELL, SO ADDITIONAL GUIDANCE ON WHERE THE BIGGEST AREAS OF NEED ARE MAY HELP ENCOURAGE ADDITIONAL RESEARCH IN SPECIFIC AREAS WHERE THERE'S PARTICULAR GAPS. >> THANK YOU. DO WE HAVE TIME FOR 1 MORE QUESTION? >> ONE MORE QUESTION. >> SO I HAVE A QUESTION FOR DR. DALE REGARDING THE GERIATRIC ASSESSMENT. SO 1 QUESTION, ACTUALLY 2 QUESTIONS, HOW WIDELY IS IT USED IN CLINICAL PRACTICE AND CLINICAL TRIALS? DO WE HAVE ANY DATA ON THAT AND ALSO WHAT ARE THE BARRIERS TO USING IT MORE WIDELY? >> THANK YOU. GREAT QUESTION. WE HAVE A LITTLE BIT OF DATA NOW ON HOW WIDELY USED IT IS. AND A SURVEY THAT'S JUST ABOUT TO COME OUT IN PUBLICATION, SOMEWHERE BETWEEN 20 AND 25% OF PEOPLE REPORT USING SOME VERSION OF A GERIATRIC ASSESSMENT IN TERMS OF USING THE FULL VERSION OF THE GERIATRIC ASSESSMENT, IT'S MUCH, MUCH, WORSE AROUND MAYBE 10% OR SO, TRIAL WISE WE'RE GETTING A LITTLE BIT BETTER, IN TERPS OF WHAT ARE THE PERCEIVED BARRIERS, THEY COME IN 2 CATEGORIES, 1 PEOPLE DO NOT NECESSARILY IDENTIFY OR RECOGNIZE THE IMPORTANCE OF DOING IT AND SO THEY DON'T INCORPORATE IT UPFRONT BECAUSE THEY'RE UNAWARE OF IT, IT THERE'S ANOTHER GROUP WHO SAY THEY'RE COMPLETELY AWARE OF THE VALUE AND AGREE WITH IT BUT FIND IT DIFFICULT FOR RESOURCE REASONS AND PERCEIVED TIME BARRIERS TO INCLUDE THEM IN TRIALS. SO AGAIN, WE HAVE TO DO BETTER TO REDESIGN THE TRIALS AND REEDUCATE PEOPLE ON THE VALUE OF THEM AND THE EASE WITH WHICH THEY CAN BE ADD TO STUDIES. THANK YOU. , I THINK WE ARE AT THE END OF OUR TIME, I WOULD LIKE TO THANK OUR PANELISTS AND ALL OF NIERK H HEAR ADDRESSING PARTICIPANTS ACROSS THE LIFESPAN SO THOUGHTFULLY BOTH IN THE POLICIES AND IN THE PREPARATION FOR THIS CONFERENCE. >> I WOULD LIKE TO ECHO THAT, THIS HAS BEEN TERRIFIC TO WORK WITH AND THANK YOU ALL. >> THANK YOU DR. BOYD AND DR. BOURGEOIS. >> THANK YOU NERVE. >> THANK YOU. >> WE WILL NOW MOVE TO TOPIC AREA NUMBER 2, STUDY DESIGN AND METRICS, WE WILL TURN THE MEETING OVER TO THE PANEL CO-CHAIRS DR. JERRY GURWITZ AND DR. PETER PEDUZVI. >> SO HI, EVERYONE. THAT WAS A WONDERFUL PANEL 1 TO START OFF THIS SERIES OF PANELS. MY NAME IS JERRY GURWITZ, AND I'M A PEDIATRICIAN AT THE UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL AND I HAVE THE PLEASURE OF CO CHAIRING THIS PANEL ON STUDY DESIGN AND MED RICKS TOGETHER WITH MY COLLEAGUE DR. PETER PEDUZZI FROM YALE SCHOOL OF MEDICINE AND WE HAVE A DISTINGUISHED GROUP OF PANELISTS DR. ALYCE, ADAMS FROM KISER PERMANENT NORTHERN CALIFORNIA, AND DR. DANNY BENIA MIN FROM DUKE INSTITUTE AND DR. SUPRIYA MOHILE, FROM UNIVERSITY OF ROUGH ATOM CHESTER. NEXT SLIDE, PLEASE. >> SO I WANT TO BEGIN WITH THE PRESIDENTIAL HEALTH BRIEFINGS HELD ON AUGUST 14th, 2020. THE REPORTERS, ONCE A VACCINE IS READY WHO SHOULD GET IT FIRST? THE RESPONSE WAS, I WOULD THINK THAT THE ELDERLY, THE PEOPLE THAT ARE MOST VULNERABLE TO THE DISEASE, MOSTLY MURING HOMES AND RETIREMENT CENTERS. THIS IS HOW MANY OF US FEEL. IN FACT THIS RESPONSE ALIGNS CLOSELY WITH THE RECOMMENDATIONS INCLUDED IN THE DRAFT REPORT ON EQUITABLE ALLOCATION OF COVID-19 VACCINE RELEASED THIS WEEK BY THE NATIONAL ACADEMY. NEXT SLIDE, PLEASE. >> PHASE 1 AND 2 VACCINE TRIALS AND THE NUMBER AT THE TOP OF EACH BAR IS THE MEAN OR MEDIAN AGE OF TRIAL PARTICIPANTS. AND IT'S VERY CLEAR THAT THESE PARTICIPANTS ARE NOT REPRESENTATIVE OF THOSE WHO MANY FEEL SHOULD BE PRIORITIZED FOR RECEIVING VACCINE. HOWEVER MANY WOULD ARGUE THAT THIS IS PERFECTLY FINE AS THAT IS NOT THE NATURE OR PURPOSE OF PHASED 1 AND PHASED 2 TRIAL. NEXT SLIDE. SO WHAT SHOULD THESE 3 PHASE TRIALS LOOK LIKE AND THIS IS A QUOTE FROM THE COMMENTARY PUBLISHED IN LANCET IN JULY, THESE SHOULD BE RAPID, PRAGMATIC AND LARGE ENOUGH TO ADDRESS EFFICACY AND SUBGROUPS OF INTEREST, OLDER ADULTS, THOSE WITH CO-MORBIDITIES WHO ARE OFTEN EXCLUDE FRIDAY CLINICAL TRIALS OR ETHNIC OR RACIAL GROUPS, MORE SEVERELY AFFECTED BY COVID-19. NEXT SLIDE. HOWEVER, IF WE START TO LOOK AT THE ELIGIBILITY CRITERIA FOR THE VARIOUS PHASE 3 TRIALS, WE BEGIN TO QUESTION WHETHER THAT WILL ACTUALLY HAPPEN. FIRST OF ALL, AS HAS BEEN MENTIONED, CHILDREN AND PREGNANT WOMEN WILL NOT BE INCLUDED. SECONDLY, THERE'S A VERY STRONG PREFERENCE FOR THE INCLUSION OF HEALTHY ADULTS VERSUS THOSE THAT THE REPORT FROM THE NATIONAL ACADEMIES PRIORITIZED FOR RECEIPT OF THE VACCINE. NEXT SLIDE. THAT IS PARENT WHEN WE SEE THE RECRUITMENT FOR THESE TRIALS. WE DON'T SEE THOSE TYPES OF PEOPLE THAT SHOULD BE PRIORITIZED. NEXT SLIDE. SO EACH OF US WILL BE INCLUDING A SLIDE WITH OUR REFERENCES AND NEXT SLIDE. SO I DO WANT TO EMPHASIZE THAT FOR THE REST OF THE HOUR WE WILL SPEND VERY LITTLE TIME TALKING ABOUT VACCINE TRIALS. WHAT OUR PANELISTS WILL BE DISCUSSING ARE APPROACHES TO STUDY DESIGN THAT CAN INCREASE THE HETEROGENERATED AITY OF TODAY POPULATIONS, APPROACHES TO ENHANCE OUR ABILITY TO APPLY FINDINGS OF TRIALS TO SPECIAL POPULATIONS LIKE CHILDREN AND APPROACHES TO SELECTING OUTCOMES THAT REALLY MATTER TO OLDER PATIENT ASKS THEIR CAREGIVERS. EACH OF OUR PANELISTS WILL LIMIT THEIR PRESENTATIONS TO 10 MINUTES AND I AM GOING TO ASK EACH OF THEM TO INTRODUCE THEMSELVES AS THEY BEGIN THEIR PRESENTATION. SO NEXT SLIDE. PETER? >> THANK YOU. I'M PETER PEDUZZI, YALE SCHOOL OF PUBLIC HEALTH. ACTUALLY WHEY WILL TALK ABOUT IS HETEROGENEITY IN [INDISCERNIBLE] INTERVENTION TRIAL WHICH IS A LARGE SCALE PRAGMATIC TRIAL. NEXT SLIDE, PLEASE. SO THE GOAL OF PRAGMATIC TRIAL IS TO YIELD GENERALIZABLE FINDINGS. IN ORDER TO DO THIS, WE NEED TO IMPROVE THE HETEROGENEOUS ROW GEANIOUS POPULATION FOR MULTILE SITES AND GEOGRAPHIC SETTINGS. SO I'M GOING TO TRY TO DO IS EXAMINE THE STRIKE FOR REPRESENTATIVE STUDY POPULATION AND EXTERNALIZABILITY. NEXT SLIDE. BRIEFLY DESCRIBE THE DESIGN AS A PRAGMATIC MULTISITE CLUSTER RANDOMIZED TRIAL TO DETERMINE THE EFFECTIVENESS OF AN EVIDENCE-BASED SECTOR MULTIFACTORIAL AND PREVENTION STRATEGY THAT WAS CONDUCTED BETWEEN THE YEARS 2015 AND 2020. EIGHTY-SIX PRIMARY CARE PRACTICES IN HEALTHCARE SYSTEMS WERE RANDOMIZED INTERVENTION, 43 PRACTICES ARE ENHANCED USUAL CARE, ANOTHER 43 PRACTICES AND IN THOSE PRACTICES WE ENROLL 5451 PARTICIPANTS. ORAL INFORMED CONSENT OR ASCENT WITH PROXY CONSENT WAS USED, INPUT FROM THE TAKE HOLDERS WAS INTEGRATED INTO PLANNING AND IMPLEMENTATION OF TRIAL. NEXT SLIDE. THIS SLIDE SHOWS GEOGRAPHIC DISTRIBUTION--1 IN TEXAS AND 1 IN CALIFORNIA. SO HEALTHCARE SYSTEMS PRETTY MUCH SPAN ACROSS THE AREA, THERE ARE HOLES WHERE WE CAN'T GET EVERYTHING IN. NEXT SLIDE. IN TERMS OF PRACTICE SELECTION, WE ASSESSED THE 162 POLITICAL PRACTICES FOR ELIGIBILITY IN THESE 10 HEALTHCARE SYSTEMS, WE SELECTED 86 PRACTICES AND THE RANGE WAS 5-12 PER HEALTHCARE SYSTEM, BASED ON THE FOLLOWING ELIGIBILITY CRITERIA. HAD TO HAVE A SUFFICIENT NUMBER OF AGE ELIGIBLE PATIENTS AT LEAST 4 HAD TO HAVE ACCESS TO COMMUNITY RESOURCES SPECIFICALLY EXERCISE PROGRAMS, ACCESS TO ELECTRONIC HEALTH RECORDS AND AVAILABILITY OF PRACTICE CHARACTERISTICS, THAT'S PRACTICE SIZE, LOCATION AND ETHNICITY. WE DID EXCLUDE 76 PRACTICES, 44 OF WHICH HAD TOO FEW AGE-ELIGIBLE PATIENTS AND 13 GEOGRAPHICALLY UNFEASIBLE TO INCLUDE SPECIALTY PRACTICES, 8 INADEQUATE EHR DATA AND 3 CO LOCATED PRACTICES. NEXT SLIDE, IF WE LOOK AT THE 86 ENROLLED PRACTICES, 91% WERE URBAN, 81% OF THE MAJORITY WERE WHITE, 93 PSYCHOFIZZISTS WERE ENGLISH SPEAKING, MEDIAN PRACTICE SIZE WAS AROUND 800 WITH THE RANGE, 568, RANGE OF PRACTICE SIZES WAS 400 TO AROUND 6000. NEXT SLIDE. SO THE ELIGIBILITY CRITERIA OF PARTICIPANTS THAT WERE ENROLLED IN THESE PRACTICE, THEY HAD TO CONTINUE WITH LIVING PERSON 70 YEARS OR OLDER AT INCREASED RISK OF FALL INJURIES THAT WERE POSITIVE ON AT LEAST 1 OF THE FOLLOWING SCREENING CRITERIA. ALL RELATED TO FIRE YEAR, FEW OR MORE FALLS FOR THE PRIOR YEAR, FEAR OF FALLING BECAUSE OF WALKING OR BALANCE PROBLEM. IT HAD TO BE ENGLISH OR SPANISH SPEAKING. THEY WERE EXCLUDE FEDERAL THEY HAD PORE 4 OR MORE ERRORS IN THE COGNITIVE SCREENING IN THE PROXY SO WE HAD MINIMAL EXCLUSION KRIST TERIAR FOR THIS TRIAL. NEXT SLIDE, PLEASE. THIS SLIDE SUMMARIZES PARTICIPANT SCREENING AND ENROLLMENT, IT'S NOT ON THE SLIDE BUT WE ACTUALLY SCREENED AC160,000 PEOPLE, INDIVIDUALS 1 OR MORE TIMES. 34,451 OF THOSE WERE POSITIVE, ROUGHLY 16,000 WERE ELIGIBLE, OF THE ELIGIBLE 10,573 DECLINED, AND WE ENROLLED 5451. SO 34% OF THOSE ARE ELIGIBLE. NEXT SLIDE. SLIDE GIVES THE GRAPHIC CHARACTERISTICS OF ENROLLED PARTICIPANTS. THE MEAN AGE WAS 80. WE HAD AN AGE DISTRIBUTION THAT SPANNED THE ELDERLY DISTRIBUTION, 41% WAS 80-89. AND 6% WERE OVER 90. MAJORITY OF THE POPULATION FEMALE 62%, MAJORITY OF WHITE 91 PERCENT, 5% WERE BLACK, 8% WERE LATINO OR HISPANIC AND MORE THAN 50% WERE COLLEGE GRADUATE OR EQUIVALENT. NEXT SLIDE. SO BRIEF POLITICAL CHARACTERISTICS, THE MEAN NUMBER OF CHRONIC CONDITIONS POPULATIONS, A THIRD OF THEM HAVE A HIP FRACT AFTER AGE 50, 5% HAD A HIP FRACTURE AFTER AGE 50, ONLY 3% IS SIGNIFICANT COGNITIVE IMPAIRMENT, 35% USE MOBILITY AND NONAMBULATORY, AND KIND OF THE 3 SCREENING QUESTIONS FOR FALL INJURY, 35% FELL 2 OR MORE TIMES IN THE PAST YEAR 39% FELL AND HURT THEMSELVES IN THE PAST YEAR AND THE MAJORITY, VAST MAJORITY HAD FEAR OF FALLING BECAUSE OF WALKING OR BALANCE PROBLEMS AND ALMOST HAEVERL THE POPULATION, 48% FEAR OF FALLING WAS THE ONLY CRITERIA THEY HAD. NEXT SLIDE, PLEASE. SO IN TERMS OF LIMITATIONS OF STRIDE, THE MAJORITY OF PRACTICES WERE URBAN WHITE AND ENGLISH SPEAKING. SOPHISTICATION RATE AMONG ELIGIBLE PERSONS WAS ONLY 34%. [INDISCERNIBLE] PARTICIPANTSS WERE MORE GENERAL EDUCATED POPULATION, THEY WERE LESS REPRESENTED RACIAL/ETHNIC GROUPS OTHER THAN WHITE AND OF PERSONS WITH SUBSTANTIAL COGNITIVE IMPAIRMENT AND HOW TO ENHANCE REPRESENTATIVENESS AND GENERALIZABILITY. NEXT SLIDE, THIS IS THE REFERENCES. AND THE NEXT SPEAKER IS DR. ADAMS. DR.AD AMS, YOU HAVE THE FLOOR. >> THANK YOU SO MUCH, MY NAME IS ALYCE, I AM A RESEARCHER AT THE KISER PERMANENT DIVISION OF RESEARCH. I WILL TALK ABOUT THE INCLUSION OF UNDERREPRESENTED POPULATIONS PRAGMATIC TRIALS AND THE SPECIFIC EXAMPLE I'M GOING TO GIVE IS THE DIABETES TELEPHONE STUDY, BEHAVIORIAL INTERVENTION THAT I LED THAT WAS FUNDED BY PC ORI, AND HAD ADDITIONAL FUNDING FROM THE AGING INITIATIVE AND NIDDK, CENTER FOR DIABETES KIDNEY RESEARCH AT THE DIVISION OF RESEARCH. NEXT SLIDE, PLEASE. SO THIS IS JUST A REPRESENTATION OF A LOT OF WHAT YOU HEARD ALREADY AND CERTAINLY DR. --PREVIOUS PRESENTERS IN PARTICULAR, DR. ADAMS-CAMPBELL TALKED TO THESE ISSUES OF RELATING TO AND PARTICULARLY TALKING ABOUT OLDER ADULTS OF COLOR IN CLINICAL TRIALS, THEY INCLUDE THINGS LIKE AWARENESS, OPPORTUNITY, ACCEPTANCE AND RETENTION SPECIFICALLY WHETHER OR NOT THESE POPULATIONS EVEN HAVE THE INFORMATION ABOUT THE EXISTENCE OF CLINICAL TRIALS THROUGH THE LOW RESOURCE SETTING WHERE THEY MAY BE RECEIVING CARE AS WELL AS THROUGH OTHER AVENUES AND WHETHER OR NOT THEY HAVE THE CAPACITY TO UNDERSTAND THE MATERIALS RELATED TO THOSE TRIALS VIA LANGUAGE OR PHYSICAL BARRIERS. OPPORTUNITYS WE HEARD ABOUT PROVIDER BIAS AND IMPLICIT BIAS PARTICULARLY WITH PROVIDERS ABOUT THEIR ASSUMPTIONTHE DESIRABILITY OF THESE PATIENTS TO PARTICIPATE AND WE JUST HEARD A LOT ABOUT ELIGE INTELLECTUAL CRITERIA AND HOW THOSE CAN ALSO HAVE AN IMPORTANT IMPACT FELT FURTHER IN TERMS OF ACCEPTANCE WE HEARD ABOUT OF THE COSTS AND FEAR AS BEING PART OF THE QUESTION IN TERMS OF SOCIAL DETERMINANTS OF HEALTH AND DRIVING THOSE THINGS AND ALSO THINGS LIKE LOGISTICAL BARRIERS AND FAMILY FACTORS AND TIME AND FINALLY RETENTION IS ALSO AN ISSUE, SORT OF ADD THE RETENTION BOX TO PRIOR INVESTIGATORS, SORT OF DEPICTION OF THIS CONTINUUM, IN THE SENSE OF RETENTION, RIGHT, WE DON'T JUST WANT THEM TO ENROLL, WE WANT THEM TO STAY AND I THINK THAT HAS TO DO WITH THE VALUE AND THE PARTICIPANTS SEE IN CONTINUING TO PARTICIPATE IN THE TRIAL. NEXT PLEASE. SO THE DIABETES TELEPHONE STUDY WAS A PRAGMATIC TRIAL OF A 5 MINUTE AUTOMATIC MATEDDICISM TOM AND SIDE EEIVET INTERVENTION PHONE CALL WITH PROVIDER FEEDBACK VIA ALERTS IN THE EHR, THIS WAS AGAIN A PC ORI FUNDED STUDY SO WE'RE AIMING TO ADDRESS PATIENT-VALUE AND IDENTIFIED OUTCOMES TO THEM, NAMELY QUALITY OF LIFE AND CHARACTERISTICS AS WELL AS PROVIDER BEHAVIOR. NOW I'M NOT GOING TO TALK SO MUCH ABOUT THE SPECIFIC IRNLT VENTION IN THE SENSE IT WAS WAS A NEGATIVE INTERVENTION, WE DID NONAPOPTOTIC THE HAVE THE IMPACT REALLY POPPED OUT ABOUT THIS STUDY THAT IS WORTH NOTE SUGGEST THAT THE LEVEL OF ENGAGEMENT OF THE PATIENTS REAMLY WAS STRIKING IN THIS STUDY AND SOME EXAMPLES INCLUDE THE 1002 OPINIONED 52 PEOPLE WE ENROLLED IN THIS STUDY,ING WE HAD A PARTICIPATION RATE OF 83%. EIGHTY-THREE% OF THE PEOPLE WHO WERE ELIGIBLE WHO WE ASKED TO PARTICIPATE SAID YES, AND 93% RETENTION RATE OF PEOPLE WITH TRIALS SO PEOPLE WHO CAME IN GENERALLY TENDED TO STAY. THEY ALSO TENDED TO BE OLDER, OLD YOUNGEST WAS SKETCH AND THE OLDEST WAS 98 WHEN HE ENROLL INDEED THE STUDY. WE ALSO HAVE 43% NONWHITE PARTICIPANTS. OUR LOWEST GROUP WAS AMONG AGENTS BECAUSE WE DID IT IN ENGLISH AND SPANISH AND DID NOT INCLUDE OTHER LANGUAGES WHICH WAS A LIMITATION OF OUR STUDY, AND WE ALSO HAD 21% WHO ARE LIVING IN LOW SOCIOECONOMIC STATUS NEIGHBORHOODS AT THE TIME OF ENROLLMENT. NEXT SLIDE, PLEASE. NO DESPITE AGAIN SORT OF THE NEGATIVE TRIAL ITSELF, THE SUCCESS WITH RECRUITMENT AND RETENTION, I THINK REALLY IS REAL REALIZE IN THE IDEA OF STAKEHOLDER ENGAGEMENT. I THINK WHAT MAKES THE STAKEHOLDER ENGAGEMENT PARTICULARLY REMARK CALVERT IS IT DOES FOLLOW PC ORI GUIDELINES WITH RESPECT TO STAKEHOLDER ENGAGEMENT AND ALL ASPECTS OF THE STUDY, SO WHAT DOES THAT MEAN LEADING TO RECRUITMENT AND RETENTION OF THESE POPULATIONS WE POKE OF BEFORE? A IF YOU EXAMPLES. IN TERMS OF AWARENESS WE USE OUR CLUSTER RANDOMIZED CONTROL DESIGN TO MAKE SURE THAT GROUPS WHO MAY OTHERWISE NOT BE AWARE, WERE AWARE OF THE STUDY IN PARTICULAR WE USED EHR TO IDENTIFY POTENTIALLY ELIGE PATIENTS AND REACH OUT TO THEM INDIVIDUALLY VIA MAIL, ET CETERA IN ORDER TO LET THEM KNOW ABOUT THE STUDY. WE CREATED FREQUENTLY ASKEDS QUESTIONS WHICH WERE CO-DESIGNED WITH WITH OUR STAKEHOLDERS IN ORDER TO REACH THOSE POPULATIONS SOPHISTICATEDY WE DID OTHER THINGS TO TRY TO TARGET THESE--BE IN THE TRIAL OR DO THE RECRUITMENT, WE ACTUALLY GAVE THEM A LIST OF THEIR PATIENTS AND SAID THESE ARE THE PATIENTS WE MAY BE APPROACHING ABOUT THIS PARTICULAR TRIAL AND GAVE THEM THE OPPORTUNITY TO OPT OUT. THAT GAVE THEM A LOG LIST AND VERY FEW OF THEM OPTED OUT ONCE WE GAVE THEM THE LIST. THE OTHER THING WE DID WAS INMYSELF EXCLUSIONS IN THE PRIOR PRESENTATION, IN TERMS OF EXCLUSIONS WE REALLY TRY TO NOT EXCLUDE PEOPLE BASED ON MUCH, SO INCLUDE PEOPLE WITH MULTIPLE CHRONIC CONDITIONS, INCLUDED PEOPLE WITH DISABILITIES AND MINOR COGNITIVE IMPAIRMENT BUT ONLY WE WE EXCLUDED WERE PEOPLE DIAGNOSED WITH DEMENTIA OR ALZHEIMERS AS WELL AS THOSE IN HOSPICE CARE, WE REALLY TRY NOT TO EXCLUDE THOSE POPULATIONS THAT WERE MOST AFFECTED BY THE CONDITION, IN TERMS OF ACCEPTANCE, ANOTHER EXAMPLE I WOULD SAY IS OUR CLINICIAN IN PARTNERSHIPS AND TERMS OF THE INTERVENTION ITSELF, IT WAS CO DESIGNED BY THE PATIENTS AND THE CLINICIANS WORKING IN CLOSE COLLABORATION WITH RESEARCHERS, WHAT MA MEAN IS THATTURE ON PATIENTS WERE PAYING ATTENTION TO EVERYTHING, FROM THE SPEED WITH WHICH THE CALLER WAS SPEAKING ON THE PHONE CALLS TO HOW MANY TIMES WE ALLOW THE PHONE TO RING INTO MAKING SURE THAT OUR PHONE CALLS WERE ACTUALLY CONSISTENT WITH EQUIPMENT BEING USED BY PEOPLE WHO ARE HEARING IMPAIRED TO ACTUALLY PARTICIPATE IN THE INTERVENTION. FINALLY IN TERMS OF RETENTION, WE REALLY FOCUSED AGAIN ON TO MINIMIZE THE BURDEN OF RESEARCH PARTICIPATION AS MUCH AS POSSIBLE. IT WAS ALSO VERY HIGH LEVEL ALTRUISM AMONG THESE PATIENTS, A DESIRE TO SAY EVEN IF THIS DOESN'T HELP ME, IT MIGHT HELP THE NEXT PERSON WHO'S BURDENED BY NEUROPATHY. NEXT SLIDE PLEASE. SO IN TERMS OF IMPLICATIONS FOR SOME OF THE COVID TRIALS WE'VE BEEN DISCUSSING AS WE DESCRIBED BEFORE, WE CAN ANTICIPATE THAT MANY OF THE SAME BARRIERS TO RECRUITMENT AND RETENTION OF UNDERREPRESENTED GROUPS WILL CONTINUE TO HAPPEN WITH COVID TRIALS UNLESS WE ARE DELIBERATE IN HOW WE THINK ABOUT IMPROVING THAT SITUATION INCLUDING SOME OF THE SPECIFIC BARRIERS LISTED HERE INCLUDING LACK OF ACTIONABLE INFORMATION, LACK OF APPROPRIATE SORT OF OPPORTUNITY, MEDIATED BY PROVIDERS OF THE HEALTH SYSTEM, ET CETERA. SO HOW DO WE DO THAT? I REALLY THINK THAT ACTIVE ITERATIVE AND ONGOING ENGAGEMENT OF STAKEHOLDERS WITHIN AND OUTSIDE OF THE HEALTHCARE SYSTEM COMMUNITY LEADERS IS CRITICAL TO SPREADING AWARENESS, ADDRESSING MISTRUST PARTICULARLY IN COMMUNITIES OF COLOR MISTRUST ASK SOME OF THE OTHER FACTORS WE TALKED ABOUT AS BEING CRITICAL BARRIERS TO THESE POPULATIONS AND IT'S MY HOPE THAT AS WE START TO THINK ABOUT COVID TRIALS WE HAVE A DELIBERATE APPROACH TO HAVING STAKEHOLDER ENGAGEMENT THROUGHOUT THE PROCESS AND TO INSURE THAT WE'RE TRYING TO REACH THESE POPULATIONS, WE HAVE MEANING EMPLOY ENGAGEMENT OF THESE STAKEHOLDERS IN THE DESIGN OF THE ACTUAL INTERVENTION AND THAT THEY CAN ALSO HELP US THINK ABOUT PRAGMATIC WAYS IN WHICH WE CAN LOWER THE BAR FOR PARDISPANTS TO PARTICIPATE AT THE SAME TIME INCREASE THE VALUE OF THEIR PARTICIPATION IN THESE TRIALS. NEXT SLIDE, PLEASE. AND THESE ARE JUDGE SOME OF THE REF FERENCES TO THINGS I'VE SPOKEN TO YOU BEFORE. THANK YOU VERY MUCH. NEXT SLIDE, PLEASE. >> THIS IS DANNY BENJAMIN. CAN YOU ALL HEAR ME? >> YES WE CAN HEAR YOU WELL, DANNY, THANK YOU. >> GREAT, THANKS SO LIKE MANY AMERICANS I'M SUPERVISING THE EDUCATION OF 4 CHILDREN AT HOME AND SO MY BAND WIDTH IS PROBABLY GOING TO MAKE IT DIFFICULT FOR ME TO SHARE VIDEO HOPEFULLY THEY WON'T SCREAM TOO MUCH IN THE BACKGROUND. THIS IS EXTRAPOLATION IN DRUG DEVELOPMENT LESSONS FROM CHILDHOOD AND IN ADDITION OF BEING DISTINGUISHED PROFESSOR OF PEDIATRICS AT DUKE UNIVERSITY I'M ALSO THE CHAIR OF THE PEDIATRIC TRIALS NETWORK WHERE WE'RE RESPONSIBLE OF THE STUDY OF 70 MOLECULES OVER THE LAST 10 YEARS FOR LABELING IN CHILDREN. IN SOME FORM OR FASHION IN THE PATHWAY ALONG DRUG DEVELOPMENT AND MY COLLEAGUES WHO TAKE CARE OF GERIATRIC PATIENTS I SAID I CAN TALK ABOUT MASTER PROT COLS, I CAN TALK ABOUT PLATFORM PROTOCOLS, WHEN I MENTIONED HOW FREQUENTLY WE USED EXTRAPOLATION, THEY WERE INTERESTED AND WANTED THAT DISCUSSED AND MAYBE LESSONS LEARNED SO EXTRAPOLATION AND DRUG DEVELOPMENT, NEXT SLIDE, PLEASE. SO NORMALLY CLINICIANS THINK OF RATE MEDICINE BUT REALLY WE WANT TO GET CONCEPTS DOWN ABOUT EXTRAPOLATION, 1 IS THE ETHICAL CONCEPT OF REPEATING UNNECESSARY STUDIES IS SOMETHING WE WANT TO AVOID AND AVOIDING STUDYING WHEN THEY'RE NEEDED IS--PHARMA CO KINETICS SAFETY AND EFFICACY EACH KIND OF LANDMARK EVENTS AND PATHWAY OF A MOLECULE AND WHEN WE THINK ABOUT EXTRAPOLATION, A LOT OF TIMES IF I ASK 8 DIFFERENT PEOPLE WHAT EXTRAPOLATION MEANS I GET 26 DIFFERENT ANSWERS BUT THERE'S ACTUALLY A REGULATORY DEFINITION THAT'S IN USE BY FDA, THE EUROPEAN MEDICINE'S AGENCY AND JAPAN AND THERE'S A FORMAL PROCESS IN USE IN PEDIATRIC DRUG DEVELOPMENT. NEXT SLIDE, PLEASE. JUST AS A REMINDER, HOW DO WE GET HERE WITH EXTRAPOLATION? AND AS FAR AS DOSING IS CONCERNED, MY ADULT COLLEAGUES AND THE HARRIET LANE AND HOSPITAL FORMULARYS SEEMS TO BE JUST TAKE THE ADULT DOSE AND YOU DIVIDE BY 70 AND THAT DOESN'T WORK WELL. AND ABOUT ONE-THIRD OF SMALL MOLECULE VS A PK SURPRISE WHICH WE PUBLISH INDEED JAMA IN 2,052,006 AND BY SURPRISE WE MEAN WHEN YOU GET THE SHARPEST FOLKS FROM THE COMPANY, YOU GET THE BRIGHTEST PEOPLE FROM FDA, YOU GET CLINICAL PHARMICOLOGYSTS, ADEEMITIONS, SUBSPECIALISTS ISSUES COMMUNITY FOLKS, ANIMAL MODELS, COMPUTER MODELS, YOU TAKE ADULT DATA AND ABOUT ONE-THIRD OF THE TIME THE SMARTEST PEOPLE ON THE PLANET AS IT RELATES TO THE MOLECULE ARE WRONG. AND THEY'RE WRONG IN A WAY THAT CAN BE EXTRAORDINARILY HARMFUL, LIKE 10 FOLD OFF, 5 FOLD OFF. AND IT'S NOT--YOU'RE NOT ABLE TO PREDICT WHETHER THEY'RE OFF BY TOO MUCH IN WHICH CASE YOU MIGHT GET TOCKS ISOTOPITY OR TOO LITTLE IN WHICH CASE YOU GET THERAPEUTIC FAILURE FROM DOSING AND IT'S NOT SOLVED BY ANIMAL MODEL STUDIES OR COMPUTERS, ET CETERA AND A LOT OF THIS, WE LEARNED HAS TO DO WITH THE FACT THAT THE ONTOGNY OF DRUG METABOLISM HAS A LOT OF DIFFERENT COMPETING PATHWAYS SO METABOLIC PATHWAYS COME ON LINE AND GET SHUT DOWN IN WAYS THAT ARE NOT PREDICTABLE ESPECIALLY ACROSS THE FIRST 24 MONTHS OF LIFE. YOU GET THE DRUG METABOLIZING OUTSIDE THE LIVER AND THINK OF THE ABOUT WHEN IT'S TRYING TO GET RID OF A MOLECULE LIKE A TRAFFIC JAM, LOTS OF ROADS GOING IN AND OUT AND VERY DIFFICULT TO PREDICT. SO MOST SURPRISES ARE IN CHILDREN LESS THAN 2 YEARS OLD, SURPRISES ARE VERY INFREQUENT IN ADOLESCENTS AND YOU CAN SEE WHEN WE TALK ABOUT AN EXAMPLE OF SURPRISES, WE'RE TALKING ABOUT LIKE LINEAR VERSUS NONLINEAR KINETIC SO YOU CAN DRIVE TO TOXICITY VERY, VERY FAST, DRUGS THAT THERE'S ALMOST NO RELATIONSHIP BETWEEN DOSING AND EXPOSURE OR A 5 OR 10 FOLD DIFFERENCE IN HOW MUCH DRUG A CHILD SHOULD GET. GO AHEAD, NEXT SLIDE, PLEASE. SO 1 OF THE THINGS WE'VE LEARNED FROM THIS IS THAT YOU SHOULD NEVER EXTRAPOLATE DOSING. YOU SHOULD NEVER EXTRAPOLATE DOSING. YOU'VE ALWAYS GOT TO DO THIS STUDY. NOW I'M SORRY FOR THIS SLIDE, IT'S PUBLICLY AVAILABLE, IT'S EXTREMELY PAINFUL AND I'M REMEDIAL FOR NOT TIGHTENING THIS UP BUT IN THE PUBLICATION FROM THE LAST DECADE, WE SHOWED THAT IN THE FIRST 10 YEARS OF THE PEDIATRIC EXCLUSIVITY PROGRAM, THERE WERE SOME VERY UNPREDICTABLE CENTRAL NERVOUS SYSTEM FINDINGS THAT PEOPLE DID NOT EXPECT IN THE FIRST HUNDRED OR 200 MOLECULES FOR WHICH EXCLUSIVITY WAS GRANTED AND THOSE DATA WERE SUBMITTED TO FDA UNDER THE TEMPERATURES OF THAT REGULATORY PATHWAY AND YOU SEE THINGS LIKE SIBLING ON SIBLING AGGRESSION, SOMINAL ENSEL, LEARNING, HYPER-ACTIVITY, SEIZURES AND THIS IS JUST THE CENTRAL NERVOUS SYSTEM EFFECTS AND THEY ARE OFTEN TIMES OFF TARGET CENTRAL NERVE SYSTEM EFFECTS, DRUGS THAT REALLY PROBABLY SHOULDN'T GIVE NEUROPSYCHIATRIC BEHAVIORS IN ADULTS OR CHILDREN DOING SO. SO THE SECOND LESSON LEARNED IS TO NEVER EXTRAPOLATE SAFETY. YOU WANT TO FIND OUT IF THE MOLECULE'S SAFE IN YOUR PATIENT POPULATION YOU'VE SIMPLY GOT TO DO THE TRIAL. NOW YOU MAY HAVE LITTLE REASON TO THINK THAT THE MOLECULE IS UNSAFE, IT MIGHT HAVE A VERY LARGE THERAPEUTIC WINDOW AND THE SAFETY SURPRISES IN CHILD DRUG DEVELOPMENT ARE MUCH LESS FREQUENT THAN THE PK AND DOSING SURPRISES. NEXT SLIDE, PLEASE. SO THIS ULTIMATELY LED TO FDA'S PEDIATRIC STUDY DECISION TREE THIS, IS PUBLICLY AVAILABLE INFORMATION AND I'LL WALK YOU THROUGH MAYBE 2 EXAMPLES. ALL RIGHT? AND YOU START WITH, SHOULD CHILDREN COMPARE TO ADULTS HAVE A SIMILAR DISEASE PROGRESSION AND RESPONSE TO THE INTERVENTION. SO THE--OR BACTERIAEREMMIA IN CHILDREN, ALSO PAIN CAN WORK THIS WAY. THAT IS WITH BACTERIAEREMMIA, THE PNEUMOCOCKAL BACTERIA REAMIA MORTALITY RATE IN CHILDREN IS MUCH, MUCH, BETTER THAN ADULTS IF IT'S TREATED BUT JUST LIKE ADULTS, IF YOU GIVE THE RIGHT DOSE OF ANTIBIOTICS IN THE POPULATION OF CHILDREN, THEY WILL DO BETTER AND IF YOU DON'T IT'S NOT GOOD. OKAY, SO, INFECTIONS TEND TO GO DOWN THE RIGHT HAND PATHWAY. IF THE ANSWER'S NO AND A GOOD EXAMPLE OF THIS IS CHRONIC LUNG DISEASE IN NEOINATES, YOU GO DOWN THE LEFT HAND PATHWAY AND THE ANSWER IS NO, YOU DO TRADITIONAL DRUG DEVELOPMENT, PK, SAFETY, EFFICACY, THE BUT YES TO BOTH--THIS HELPS IN OTHER PATIENT POP IEWLTZS IF IT'S REASONABLE THAT THE DISEASE AND EXPOSURE OUTCOME RELATIONSHIPS ARE SIMILAR THEN YOU CAN KIND OF GO DOWN ALL THE WAY TO OPTION C IN WHICH CASE YOU DO PK AND SAFETY STUDIES. IF THE ANSWER TO THAT IS NO, AND YOU HAVE A PHARMA CO DYNAMIC MARKER, SO FOR EXAMPLE, A PAIN SCORE OR A BLOOD CULTURE, THEN YOU CAN DO PKPD STUDIES TO ESTABLISH THAT RELATIONSHIP BETWEEN EXPOSURE AND OUTCOME AND IF YOU DO NOT, THEN YOU GO BACK OVER TO DOING THE FULL DRUG DEVELOPMENT PLAN. NEXT SLIDE, PLEASE. SO JUST AS A REMINDER PK IS WHAT THE BODY DOES TO THE DRUG AND PD, PHARMA CO DYNAMIC SYSTEM WHAT THE DRUG DOES TO THE BODY. AND I THINK WITHIN TRIALS IT'S BECOME KEY IN CHILDREN'S TRIALS IN PARTICULAR BUT ALSO WE'RE LEARNING THIS IN ADULT TRIALS TO NEST IN PHARMA KINETIC AND PHARMA CO DYNAMIC BOTH EXPOSURE EFFICACY OUTCOMES AND EXPOSURE SAFETY OUTCOMES AND THIS HELPS US DEVELOP VALIDATED PHARMA CO DYNAMIC END POINTS IN A REGULATORY SENSE RATHER THAN AN INVESTIGATOR SAYING HEY, I HAVE A PHARMA CO DYNAMIC END POINT. AND TO ADVANCE PUBLIC HEALTH. GO,A HEAD, NEXT SLIDE, PLEASE. SO WHAT'S THE PUBLIC HEALTH VALUE ADD? MANY CLINICIANS VIEW EXTRAPOLATION AS A MEAN OF LAST RESULT TO PROVIDE PATIENT CARE BUT EXTRAPOLATION BEING BE A 4FUL TOOL THAT BENEFITS PUBLIC HEALTH F. WE HAVE A COMMON UNDERSTANDING AND DEFINITION OF IT,S IF WE HAVE A FORMAL ASSESSMENT OF WHEN IT SHOULD AND SHOULD NOT BE USED FOR EXAMPLE, WE USED TO THINK YOU COULD EXTRAPOLATE ANTIDEPRESSANT STUDIES AND CLEAREE WE LEARNED YOU CANNOT. MIGRAINE STUDIES WE THOUGHT THAT YOU COULD EXTRAPOLATE, CLEARLY YOU CANNOT, SO NEED TO HAVE FORMAL ASSESSMENT OF WHEN IT SHOULD AND SHOULD NOT BE USED AND FOCUS OUR EFFORTS ON REQUESTIES THAT SHOULD BE ANSWERED. WE DON'T HAVE TO REPLICATE EVERY EFFICACY TRIAL IF WE GET DOSING AND SAFETY, AND PK/PD RELATIONSHIPS CORRECT. AND VIA THE FORMAL PROCESS OF EXTRAPOLATION, PEDIATRICS WE WE'VE LEARNED IT CAN BE USED FOR EFFICACY AND IT REALLY CAN BENEFIT YOU FROM TAKING A DRUG AND A PATIENT POPULATION WHERE THIS STUDY'S NOT FEASIBLE TO SOMETHING CAN YOU DO AND BENEFITS PUBLIC HEALTH BUT YOU SHOULD NOT DO IT FOR SAFETY AND YOU SHOULD CERTAINLY NOT DO IT FOR DOSING. NONAPOPTOTIC YOU THIS EQUATION HERE MIGHT ISSUE DIFFERENT IN THE GERIATRIC POPULATION BECAUSE CLINICAL PHARMICOLOGY IS A LITTLE LESS COMPLEX ALTHOUGH NOT REALLY WELL DESCRIBED IN SOME OF THE REAL ELDERLY PATIENTS. AND THEN, POTENTIAL POWER OF THIS USE IS IT ALLOWS US TO FOCUS OUR EFFORTS ON FEASIBLE STUDY THAT IMPROVE THE HUMAN CONDITION BECAUSE IT'SIE WHOLE LOT LESS EXPENSIVE TO DO MULTIPLE PK/PD STUDIES THAT ARE WELL DESIGNED THAN MULTIPLE RANDOMIZED CLINICAL EFFICACY WITH THAT I WILL GO TO REFERENCES, WHILE ME NEXT CLEEPG IS REPAIRED TO SPEAK, THANKS. >> I'M JUST GOING TO DO A SOUND CHECK, CAN YOU HEAR ME? THANK YOU DR.AD AM AMILLIOS, I CAN SEE YOU RIGHT IN CENTER OF MY SCREEN. HI, EVERYONE, I APPRECIATE THIS WHOLE DAY AND WE ALL DO WORK IN THIS AREA, BUT IT'S NICE TO BE ABLE TO SIT AND REALLY THINK ABOUT HOW TO IMPROVE OUR PROCESSES FOR CLINICAL TRIAL DESIGN AND I LEARNED A TON THUS FAR. I AM A GERIATRIC ONCOLOGIST, I WORK AT THE UNIVERSITY OF ROUGH ATOM CHESTER AND I AM 1 OF THE LEADS WITH DRS. WILLIAM, DALE AND [INDISCERNIBLE] RESEARCH AGING GROUP AND OUR GOAL IS REALLY TO HELP DESIGN CLINICAL RESEARCH ESPECIALLY TRIALS TO UNDERSTAND BETTER HOW TO IMPROVE OUR DATA ON SAFETY AND EFFICACY IN OLDER ADULTS. ESPECIALLY THOSE THAT ARE UNDERREPRESENTED, THOSE WITH CO MORBIDITIES AND MEDICAL PROBLEMS THAT DON'T FACILITATE ACCRUAL. --SO TREATMENTS ARE ONLY AVAILABLE TO THE FITTEST, HEALTHIEST, YOUNGER PATIENTS AND THE DATA IS ONLY APPLICABLE TO THOSE PATIENTS, YET WE USE THE TREATMENTS IN CLINICAL PRACTICE FOR OLDER ADULTS ALL THE TIME AND THEY'R OFTEN HARMED DUE TO LIMITED THERAPEUTIC BENEFIT. I DO THINK CLINICAL TRIALS WOULD BENEFIT FROM REALLY WORKING WITH STAKEHOLDERSAs DR. ADAMS TALKED VERY ELOQUENTLY ABOUT AND PARTNERING WITH STAKEHOLDERS TO DETERMINE THE OUTCOMES THAT REALLY MATTER TO OLDER ADULTS AND THEIR CAREGIVERS MPLET NEXT SLIDE. SO WHEN WE THINK ABOUT CLINICAL TRIAL DESIGN AND ONCOLOGY, THERE ARE CERTAIN STANDARDS THAT ARE ACCEPTED BY OUR STRUCTURE WHETHER IT'S THE INVESTIGATORS, THE COOPERATIVE GROUPS, THE INSTITUTIONS, THE FDA, THE NIH AND THOSE PARAMETERS ARE THE OUTCOMES, SURVIVAL, PROGRESS FREE SURVIVAL, RESPONSE RATES, GRAY GRADE 3-5 TOXICITY AND TREATMENT AS MEASURED BY THE CLINICIANS AND NOT NECESSARILY THE PATIENTS. THESE OUTCOMES ARE IN CONFLICT WITH WHAT WE TALK ABOUT WITH PATIENTS IN THE CLINIC AND WE HAVE A GERIATRIC ONCOLOGY CLINIC WHERE WE PREFER TO SEE PATIENTS 65 AND OVER AND WHEN WE'RE TALKING TO PATIENTS, THEY CAN ASK US ABOUT FUNCTION. THEY ASKED US ABOUT THEIR MEDICAL PROBLEMS AND HOW TREATMENTS MAY AFFECT OTHER MEDICAL PROBLEMS. THEY ASK US ABOUT THE MEMORY, THEIR MOOD, THEIR SOCIAL SUPPORT AND THEY REALLY WANT TO KNOW FROM US AS THEIR DOCTORS AND THEIR CLINICIANINGS HOW WILL I TOLERATE TREATMENT. NEXT SLIDE. AS DR. DALE EXPLAINED IN THE PREVIOUS SESSION, THE GERIATRIC ASSESSMENT IS A TOOL BOX THAT IS UTILIZED FBI GERIATRICIAN TO ASSESS THE HEALTH DOMAINS THAT ARE IMPORTANT PREDICTORS OF MORTALITY IN OLDER ADUTS. THESE THESE ARE LIST INDEED THE FIGURE, THEY CAN BE MEASURED BY STANDARDIZED TOOLS AND THOSE TOOLS ARE AVAILABLE TO ANY INVESTIGATOR THAT UPONS TO USE THEM OR CONSIDERING THEIR DESIGN TRIALS FOR OLDER ADULTS. WE KNOW IN ONCOLOGY GERIATRIC ASSESSMENT CAN HELP US IDENTIFY PATIENTS OF HIGHEST RISK OF TOXICITY AND MORTALITY, CARE MANAGE EXPMENT CAN IMPROVE CLINICAL OUTCOMES AND CLINICAL CARE. AND WE CONDUCTED A PC ORI FUNDED STUDY THAT SHOWED THAT WHEN WE PROVIDE GERIATRIC ASSESSMENT INFORMATION TO ONCOLOGISTS IN CLINICAL CARE, THEY TALK MORE ABOUT THE OUTCOMES THAT MATTER TO OLDER ADUTS AND THEIR CAREGIVERS AND IT ALSO LEADS TO IMPROVED PATIENT AND CAREGIVER SATISFACTION AND THIS IS IN THE JUDGE, AMA ONCOLOGY IN 2018. NEXT SLIDE. AND AN RO1 FUNDED RESEARCH FROM THE NCI, WE ALSO EVALUATED IN A CLUSTER RANDOMIZED DESIGN WHETHER PROVIDING INFORMATION TO ONCOLOGISTS IMPROVES OR CAUSES ONCOLOGISTS TO CHANGE THEIR DECISION MAKING PROCESS ABOUT TREATMENT DOSING AND SO, ONCOLOGISTS STRUGGLE WITH WHAT TREATMENT DOSING TO PROVIDE TO THE OLDER ADULTS THEY'RE SEEING IN THEIR CLINICS BECAUSE THESE PATIENTS WITH EFFICACY WERE DEVELOPED IN TRIALS THAT DID NOT INCLUDE THE PATIENTS THEY'RE SEE NOTHING THEIR CLINIC AND WE SEE THAT THE OUTCOMES HERE WHERE CLINICIAN RATED TOXICITY SURVIVAL TREATMENT DECISIONS AND ALSO PATIENT REPORTED TOXICITS AS MEASURED BY PRO CACE WHICH IS A MEASURE BEING DEVELOPED BY THE NCI, NEXT SLIDE. WE WERE ABLE TO ENROLL 718 PATIENT WHO IS HAD A GERIATRIC DOMAIN INPAIRMENT AND WE DID THIS GERIATRICKIZATION RAT RICK ASSESSMENT DOMAIN INPAIRMENT SO OUR GOAL WAS TO INCLUDE PATIENTS WHO WERE NORMALLY EXCLUDED FROM OTHER GERIATRIC TRIALS AND WE DID THIS IN A SHORT PERIOD OF TIMA BECAUSE WE ALSO WORK WITH STAKEHOLDERS AND THIS WAS AN IMPORTANT CLINICAL QUESTION THROUGH THE ONCOLOGIST THROUGH THE PATIENTS AND CAREGIVER WHO IS HAVE BEEN ROLLING ON TO OUR STUDIES. OUR ELIGIBILITY FOR THOSE AGE 70 AND ABOVE AND THAT THEY HAD AT LEAST 1 DOMAIN IPT GREATER PAIRMENT AND WHAT WE FOUND WAS A HIGHER REFULENCE OF IMPAIRMENT THAN WE EXPECTED. THESE PATIENTS WERE ENROLLED IN THE COMMUNITY. THEY WERE ALL RECEIVING CHEMO THERAPY OR STARTING A CHEMO THERAPY REGIMEN, OVER 90% HAVE SERIOUS PHYSICAL PERFORMANCE DEFICITS OVER A THIRD HAD COGNITIVE IMPAIRMENT AND MANY HAD OTHER DEFICITS THAT REALLY WOULD INCREASE THEIR RISK OF POOR OUTCOMES FROM TREATMENT, NEXT SLIDE. WE FOUND--ONCOLOGISTS WHO RECEIVE GERIATRIC ASSESSMENT INFORMATION DOSE REDICED TREATMENT OF CYCLE 1 AND THESE PATIENTS WERE GETTING TREATMENT FOR PALLIATIVE INTENTION, NOT CURE INTENTION, WE ALSO FOUND THAT THE INTERVENTION IMPROVED THE LOWER TOXICITY FOR PATIENTS ENROLL FROM 70% IN USUAL CARE TO THE 50% IN THE INTERVENTION GROUP. SO WHEN WE THINK ABOUT OUTCOMES, IT REAMLY WORKING WITH PATIENTS TO UNDERSTAND THAT WHAT THEY WANT AS AN OUTCOME IN OUR CLINIC, MANY OF MY OLDER PATIENTS WILL TELL ME I WANT TO REMAIN INDEPENDENT, I DON'T WANT TREATMENT TO CAUSE ME TO GO INTO THE HOSPITAL, I WANT TO STAY AT HOME, I WANT TO BE FUNCTIONAL SO THE FRIENDS OF CANCER RESEARCH IS AN ORGANIZATION THAT IS WORKING WITH MULTIPLE PARTNERS IN THE HEALTHCARE SYSTEM AND HAS BEEN ADAPTING OUTCOMES TO REALLY INTEGRATE THE PATIENT EXPERIENCE AND WE'RE THINKING ABOUT CANCER TREATMENT TOLERABILITY WITH A BROUGHTER PERSPECTIVE OF INTEGRATING THE PATIENT EXPERIENCE THINKING ABOUT THE SIDE IMPACT AND HOW THAT MIGHT AFFECT THE ABILITY OR DESIRE OF THE PATIENT TO ADHERE AND ALSO REALLY MEASURING FROM THE PATIENT HOW THEY ARE FEELING AND FUNCTIONING WHILE ON TREATMENT IN CLINICAL TRIALS. THANK YOU. >> SO THIS IS JERRY GURWITZ AGAIN, THOSE WERE FANTASTIC PRESENTATIONS AGAIN, THANK YOU. I WANT TO BEGIN OUR DISCUSSION WITH A QUESTION FOR SUPRYA, AND I GUESS I WANT YOU TO EXPAND ON THE PATIENT EXPERIENCE RELATING TO TRIALS FOR CANCER TREATMENTS IN OLDER ADULTS AND AS I READ, YOU KNOW, THE TOP TIER JOURNALS LIKE NEW ENGLAND JOURNAL OF MEDICINE, I RARELY SEE AN ASSESSMENT OR DESCRIPTION OF PATIENT EXPERIENCE IN THOSE PAPERS. AND I JUST WONDERED IF BECAUSE THIS IS A SESSION ON METRICS, CAN YOU TALK ABOUT HOW THAT MIGHT BETTER HAPPEN? >> YEAH, I THINK WE NEED TO REALLY UPROOT THE STRUCTURE OF HOW WE DO CLINICAL TRIALS AND HOW WE'RE THINKING THROUGH THE RESEARCH QUESTIONS AND THE DESIGN AND THAT AS YOU SAID IS RELATED TO DESIGN AND METRICS. COUPLE POINTS. I THINK THAT THOSE WHOM HAVE EXPERTISE IN RECRUITING PATIENTS THAT REFLECT THE POPULATION TO HAVE A SEAT AT THE TABLE. SO IF WE ARE THINKING THROUGH DESIGNING A TRIAL FOR OLDER ADULTS, THERE SHOULD BE PEOPLE WITH AGING EXPERTISE, GERIATRICIANS WHO ARE SITTING IN THE ROOMS WHERE THE DESIGN IS HAPPENING AND THE APPROVAL PROCESSES, FOR EXAMPLE, AT THE NCI STEERING COMMITTEE AND IN THAT WAY WE CAN CAN IMPROVE DESIGN BETTER IN ADDITION WE HAVE TO WORK WITH THEIR PATIENTS AND THEIR FAMILIES AND WE SHOULD NOT BE ISOLATED FROM WHAT MATTERS TO THEM AND SO THEY SHOULD ALL BE SITTING AT THE TABLE WITH US AS WE THINK THROUGH OUR DESIGN CONSIDERATIONS. WE HAVE TO CONSIDER BOTH STRUCTURE AND INCENTIVES AND HOW OUR TREATMENTS ARE PAID FOR AND WHY OUR STRUCTURE ALLOWS US TO CONTINUE THESE AND PERPETUATE THESE INBALLANCES AND INEQUITY OVER TIME. UNTIL WE HAVE POLICY CHANGES, THE SAME THING WILL CONTINUE TO PERPETUATE, YET WE'VE SEEN IMPROVEMENT, THIS WHOLE DAY TODAY IS EDUCATION ABOUT HOW WE CAN IMPROVE, WE NEED TO BE ABLE TO REACT TO WHAT WE'RE LEARNING TOGETHER AND HAVE PEOPLE WORK TOGETHER TO CHANGE STRUCTURE SO THAT FUTURE CLINICAL TRIALS CAN ADDRESS THE NEEDS OF OUR OLDER ADULTS. >> THANK YOU. PETER, I WONDER IF YOU CAN COMMENT ON THIS ISSUE. I THINK AT LEAST MANY OF US HAVE BEEN TAUGHT THAT THE PRAGMATIC CLINICAL TRIAL DESIGN, THE PURPOSE OF IT IS TO--1 OF THE PURPOSES IS TO IMPROVE REPRESENTATIVENESS AND GENERALIZABILITY BUT YOU SORT OF POINTED OUT THAT THAT ISN'T ALWAYS THE CASE. SO DO HAVE YOU ANY SUGGESTIONS ABOUT HOW TO ENROLL MORE HETEROGENEOUS OR DIVERSE POPULATIONS TO PRAGMATIC TRIALS? YOU'RE ON MUTE, PETER. >> DESPITE ALL EFFORTS WITH A LARGE PRAGMATIC TRIAL, WE FELL SHORT ON REPRESENTATIVE PIECES OF THE STEM POPULATION EVEN THE NEWS, WE HAD LOCAL AND NATIONAL STAKEHOLDER ENGAGE WANTS SO DURING THE COURSE OF THE TRIAL WE HAD RECRUITMENT ISSUES AND WE HAD TO EXTEND RECRUITMENT AND THAT'S TYPICAL OF A LOT OF TRIALS THAT RECRUITMENT IS AN ISSUE. SO, WHEN YOU ARE FOCUSING ON RECRUITMENT, SOMETIMES YOU LOSE SITE OF WHO YOU'RE ACTUALLY RECRUITING SO YOU HAMMER OR ENCOURAGE INVESTIGATORS AND SITES TO RECRUIT MORE AND MORE CAN IT BECOMES LESS OF A FOCUS ON THE ACTUAL REPRESENTED POPULATION ACTUALLY IS, SO YOU REALLY NEED TO ADDRESS THIS UP FRONT. WE WILL NEED TO HAVE STRATEGIES FOR RECRUITING HETEROGENEOUS ROW GENIUS POPULATION SAYS AND ONCE THE TRIAL GETS UP AND ROLLING SOMETIMES IT'S TOO LATE, YOU KNOW, PERHAPS SOME OF THE METHODS FROM IMPLEMENTATION SCIENCE COULD BE USED TO LOOK AT BARRIERS AND MAY HELP OUT BUT MY EXPERIENCE HAS BEEN UNLESS IT'S UPFRONT IT'S MUCH HARDER DOWN THE ROAD TO RECRUIT A HETEROGENEOUS POPULATION AND JUST 1 FINAL COMMENT ON TRIALS. SOMETIMES IMPEDIMENT IN TRIAL IS THE COMPLEXITY. AND I THINK THERE NEEDS TO BE YOU KNOW PRAGMATIC TRIALS, TRY TO BE HETEROGENEOUS ROW GENIUS AND AT LARGE, I THINK THEY NEED TO BE TAKING 1 STEP FURTHER AND THINK ABOUT THE CONCEPT OF LARGE SAMPLE TRIALS THAT'S BEEN ADVOCATED IN THE UK WHERE THE TRIALS ARE REALLY BIG AND THE POPULATIONS ARE VERY HETEROGENEOUS, AND THE DESIGN TO INFORM PUBLIC HEALTH QUESTIONS TO IMPLEMENT THERAPIES OR INTERVENTIONS THAT COULD BE READILY ADOPTED IN PRACTICE. SO I THINK THE PRAGMATIC TRIALS NEED TO MOVE A BIT FURTHER MORE TOWARDS SIMPLICITY AND MOST PRAGMATIC TRIALS ARE MORE EXPLANATORY AND PRAGMATIC ANYWAY. THOSE ARE JUST MY THOUGHTS BUT I REALLY WANTED TO GET DR. ADAM'S THOUGHTS. I ENJOYED HER PRESENTATION, ALYCE, YOU REFER TO BARRIERS OF RETENTION AND UNDERREPRESENTED POPULATIONS IN CLINICAL TRIALS, CLEARLY WE'RE STRUGGLING WITH THIS, ARE THERE RESEARCH DESIGN CONSIDERATIONS THAT ARE POSSIBLY ADDRESS THIS UPFRONT? >> ABSOLUTELY SO SUPRIA TALKED ABOUT THIS AS WELL. I DON'T THINK THERE'S 1 THING WE DO, IT'S DIFFERENT THINGS WE HAVE TO SOPHISTICATED AND DIFFERENT STAGES MIGHT NEED TO BE ADAPTABLE AND FLEXIBLE IN THOSE NEEDS. SO IN EMERGING ITS OF DOING THINGS UP FRONT THE RESEARCH QUESTION IS THE MOST IMPORTANT THING. I HAVE'S QUESTION JUST THE OTHER DAY FROM AN ONCOLOGY WERER TO SAY, YOU KNOW I FEEL LIKE AFRICAN AMERICANS COULD BENEFIT FROM THIS WHY AREN'T THEY SIGNING UP AND MY INSTINCT WAS TO LOOK AROUND AND SAY ARE YOU ASKING A QUESTION THAT IT'S IMPORTANT TO THE COMMUNITY IS THAT YOU WANT TO RECRUIT? AND YOU HAVE TO BE ABLE TO ANSWER THAT QUESTION. IF YOU CAN'T ANSWER THAT QUESTION, YOU'RE TOO FAR, TOO DISTANT FROM THE POPULATION YOU'RE TRYING TO AFFECT AND HAVING THOSE INDIVIDUALS ON THE TEAM IS IMPORTANT AND I WANT TO SPEAK FOR A MOMENT ABOUT IN TERMS OF THE DESIGN OF THE STAKEHOLDER INTERVENTION, WHEN WE STARTED OUR STUDY, WE HAD 3 INDIVIDUALS OF VARYING RACIAL AND GENDER MAKE UP ALL OF WHOM HAVE THE CONDITION WHO WE KNEW ABOUT, PART OF OUR SYSTEM AND WANTED TO PARTICIPATE. WE FOUND OUT VERY, VERY QUICKLY THAT IT WAS UNFAIR TO ASK THEM TO REPRESENT ALL PEOPLE WITHIN THEIR SPECIFIC SUBGROUP AND THEN FURTHER MORE THAT THERE WERE OTHER ASPECTS OF THIS WE COULD NOT CONSIDER BASED ON THEIR OWN EXPERIENCE. SO OUR DIRECTION THEN WAS TO SAY WE NEED MORE, WE NEED MORE INPUT FROM STAKEHOLDERS TO MAKE THIS HAPPEN AND SO WE WENT OUTSIDE OF OUR CLINICAL SYSTEM TO SAY WHERE ARE THERE PATIENT ADVOCACY GROUPS OR PATIENT SUPPORT GROUPS AROUND PERIPHERAL NEUROPATHY WHO MIGHT BE LETTING US IN TO PRESENT WHAT WE'RE THINKING ABOUT AND GIVE US FEEDBACK ALONG THE WAY. SO IN THE END WE STARTED OUT WITH 3 PATIENTS AND ENDED WITH 30 STAKEHOLDERS CONTRIBUTING THROUGHOUT THE STUDY IN TERMS OF GIVING US FEEDBACK AND ONGOING FEEDBACK SO WE RAN INTO ROAD BLOCKS, WE WENT BACK AND SAID HEY, WE RAN INTO A ROAD BLOCK WHO DO YOU THINK AND THEY HELPED US THINK THROUGH DIFFERENT STRATEGIES OF RECRUITMENT AND SORT OF SPECIFIC--IT'S TROUBLING BECAUSE THE PRIOR WORK WE HAD DONE SHOWED THOSE GROUPS WHEN THEY HAD SYMPTOMS OF NEUROPATHY WERE LESS LIKELY TO GET A DIAGNOSIS AND IT WAS MIGHT HAVE BEEN IT WAS A CLINICALLY APPROPRIATE THING BUT MY INSTINCT BASED ON THE DATA WE WERE SEEING IS THEY SIMPLY WEREN'T BEING ASSESSED IN THE SAME WAY. SO I THINK WE NEED TO BE REALLY THOUGHTFUL ABOUT WHAT WE MEAN BY ENGAGEMENT AND BY WHOM AND WE REALLY NEED TO BE THOUGHTFUL ABOUT WHICH SUBGROUPS ARE MOST LIKELY TO BE AFFECTED AND HOW DO WE REACH OUT TO THEM SUCCESSFULLY BUT IT STARTS WITH THE FIRST QUESTION, RESEARCH QUESTION AND MAKING HUR THAT RESEARCH QUESTION IS RELEVANT NOT ONLY TO CLINICIANS AND RESEARCHERS BUT BY PATIENTS AFFECTED BY THE TREATMENT. >> THANK YOU. IF WE DON'T DO A GOOD JOB WE CAN'T LOOK AT THE EFFECTIVE TREATMENT IN AGE GROUPS IN CERTAIN UNDERREPRESENTED POPULATIONS. REMINDS ME BACK IN THE DAYS FOR CORONARY BYPASS SURGERY [INDISCERNIBLE] NOW WE'VE IMPROVED A LOT FOR STAFF AND WE NEED A LOT MORE IMPROVEMENT IN TERMS OF THE TIMES OF PEOPLE SO WE CAN GENERALIZE TO THE POPULATION. THANK YOU. AND THE LAST QUESTION IS TO DR. BENJAMIN. OUR UNDERSTANDING OF COVID-19 PHASE 3 TRIALS, ARE THEY EXCLUDING CHILDREN? THEY'RE EXCLUDING CHILDREN? DOES THAT BOTHER YOU? THE EXTRAPOLATION PRINCIPLES YOU'VE DESCRIBED PROVIDE ANY COMFORT FOR THIS? >> WELL, NUMBER 1, YOU CAN'T EXTRAPOLATE SAFETY AND YOU CAN'T EXTRAPOLATE DOSING SO, COMPLETE EXCLUSION IS OF COURSE UNETHICAL. YOU REALLY WANT TO HAVE SOME INDICATION OF BENEFIT SO AT THE END OF PHASE 2, UNDER THE AMERICAN SYSTEM IS WHEN YOU START TO ENGAGE CHILDREN. SO IF YOU'VE GOT MOLECULES, OR VACCINES WHERE YOU'VE GOT SOME INDICATION OF EFFICACY AND SAFETY FOR EXAMPLE, PART WAY THROUGH THESE PHASE 3 TRIALS WHETHER IT'S A VACCINE OR A SMALL MOLECULE, THAT'S THE TIME TO EXPAND WHERE THE MORAL IMPERATIVE IS TO EXPAND AND TO CHILDREN AND THAT'S NUMBER 1. AND NUMBER 2 GOING BACK TO DR. ADAM'S POINT, I THINK ALL SEGMENTS OF SOCIETY WHETHER IT'S YOU KNOW THE NIH OR ELSEWHERE IS REALLY FUMBLES THE BALL AS IT RELATES TO CHILDREN AND COVID-19 TH LACK OF CHILDREN IN ANY OF THESE TRIALS AND THE LACK OF PLANNING TO HAVE CHILDREN IN ANY OF THESE TRIALS AND THE FACT THAT YOU KNOW WE'VE GOT 50 MILLION SCHOOL CHILDREN AND WE'VE GOT REALLY NO STUDIES GOING ON AS TO HOW TO KEEP THEM FACE-TO-FACE, GET THEM FACE-TO-FACE, WHAT ARE THE CONSEQUENCES AS IT RELATES TO FACE-TO-FACE SCHOOLS, THE SMALL DOLLARS FOR CHILDREN'S HEALTH AND IT RELATES TO COVID IS GOING TO SOMETHING THAT WILL AFFECT A COUPLE HUNDRED CHILDREN RATHER THAN THE 50 MILLION CHILDREN. I THINK IF YOU LOOK AT THE LONG-TERM IMPACT OF COVID-19, IT'LL BE THE DEFINING EVENT FOR THIS GENERATION AS IT RELATES TO DISPARITIES, HEALTH, MENTAL HEALTH, PHYSICAL HEALTH, WILL BE OUR ABILITY TO HAVE THEM MEANINGFULLY AND SAFELY AND FACE-TO-FACE SCHOOL INSTRUCTION. SO YES, IT'S A CONCERN, YES IT'S A BROADER CONCERN THAT YOU NEED PLANNING BECAUSE YOU WILL NEED BROADER PLANNING TO GET THEM INTO LATE PHASE 2 AND YOU KNOW WE--AS IT RELATES TO COVID-19 IN CHILDREN, WE'RE FUMBLING AROUND WITH DECK CHAIRS WHEN WE'RE GOING FULL SPEED INTO AN ICEBERG, THANKS. >> YEAH, SO WHAT I'M HEARING IS THAT THEY'RE IN PHASE 3, MY UNDERSTANDING OF SOME OF THESE VACCINE TRIALS AND 1 OF THE PROBLEMS IS MINORITIES AND I DON'T BELIEVE THERE ARE ANY CHILDREN. >> THAT'S CORRECT, ALTHOUGH YOU WOULD PROBABLY HERE, THIS IS PROBABLY A BIT TOO, THIS MIGHT BE TOO DETAILS AND I'M SORRY FOR INTERRUPTING BUT HERE THE CONCERN IS THAT THERE'S NO PLAN FOR CHILDREN. LIKE IF I COULD WAVE A MAGIC WAND OVER THESE VACCINE TRIALS IT WOULD--USE AUTHORIZATION OF USAGE OF COURSE AT THAT TIME YOU WANT TO SEE CHILDREN ENROLLED IN TRIALS. WE HAVE ESSENTIALLY SKIPPED PHASE 2 FOR A LOT OF THESE VACCINE TRIALS, WE'VE ONLY DO PHASE 1 O A REASONABLE PERSON COULD SAY, I WANT TO GET HALFWAY THROUGH THE PHASE 3 TRIAL IN ADULTS BEFORE I START ENROLLING OR SETTING UP MY PEDIATRIC PROGRAM AND THAT'S--THAT'S A REASONABLE VIABLE ETHICAL PATHWAY, IT'S THE TOTAL EXCLUSION AND TOTAL LACK OF PLANNING. >> YEAH, I HAVEN'T HEARD THAT THINKING WAS AS LEAST EXTENT, THE TRIALS ARE DONE AND WE MIGHT HAVE A ACSEEN WITH LICENSE AND THEN HAVE YOU POPULATIONS OUT THERE THAT YOU DON'T KNOW AND HOW IT WILL AFFECT THOSE POPULATIONS THEY HAVE IN THE STUDY. THAT'S MY ANSWER. >> YOU'RE TOTALLY ON POINT. YOU'RE TOTALLY CORRECT. >> YEAH, BRINGING IN THE CHILDREN AT SOME POINT BUT I HAVEN'T SEEN THAT ARTICULATED. THANK YOU. >> THEY'RE BEING IGNORED IN THE PANDEMIC. THANKS. >> YEAH, THANK YOU. >> SO THIS IS JERRY GURWITZ, AGAIN, THAT WAS AN AMAZING NUMBER OF PRESENTATIONS AND QUALITY OF PRESENTATIONS BY OUR PANELISTS. I WANT TO THANK EVERYBODY. I DO NOT SEE ANY ADDITIONAL QUESTIONS COMING IN. IF THERE ARE ANY PLEASE LET ME KNOW, OTHERWISE I DO WANT TO THANK ALL THE PANELISTS FOR THEIR WONDERFUL PRESENTATIONS AND VERY INTERESTING DISCUSSION. SO THANK YOU. >> LIKEWISE. >> CAN I ASK 1 QUESTION? THIS IS FOR THE GERIATRICIANS ON THE PANEL. DO YOU ALSO FOR DR. BENJAMIN, ARE YOU AWARE OF ANY GUIDELINES RELATED TO OLDER ADULTS ESPECIALLY ADULTS WITH CO-MORBIDITIES AND [INDISCERNIBLE] KIED LINES THAT ARE ANALOGOUS THAT DR. BENJAMIN TALKED ABOUT WITH CIRCUMSTANCES WHEN EXTRAPOLATION IS NOT AS DANGEROUS AND SHOULD BE AVOIDED? >> SO-- >> I'LL MAKE A RESPONSE. YOU KNOW THAT, I THINK 1 OF THE GREAT THINGS ABOUT OUR PANEL WAS THE DIVERSITY OF OUR PANEL AND THE FACT THAT DANNY WAS ON OUR PANEL BECAUSE THE EXTRAPOLATION CONCEPT IT WAS TOTALLY NEW. IT WASN'T AT ALL HOW GERIATRICIANS THINK, PARTICULARLY ABOUT THERAPEUTIC, SAFETY AND EFFICACY. SO THAT'S WHY WE FOUND IT SO INTRIGUING SO I AM NOT AWARE OF ANY OVERLAP IN THINKING BETWEEN WHAT DANNY PRESENTED AND THE WAY THAT GERIATRICIANS ARE THINKING ABOUT THE OLDER ADULT POPULATION. >> DANNY DID YOU WANT TO MAKE A FINAL COMMENT? >> NO, I THINK YOU'RE CORRECT AGAIN. >> YEAH,--GO,A HEAD,. >> I WOULD LIKE TO MAKE A COMMENT TOO, THIS IS SUPIRYA,. >> I WAS JUST AGREEING AND I'M NOT AWARE OF FORMAL DOCUMENTS, THANKS. >> YEAH, IN THE CANCER WORLD THERE IS ALMOST NO INFORMATION ON THE IMPACT OF POLYFORMACY ON CANCER TREATMENT, THERAPEUTIC SAFETY AND EFFICACY AND IT'S A HUGE GAP IN KNOWLEDGE AND IT'S--IT'S ACTUALLY DISTRESSING TO CLINICIANS LIKE ME WHO CARE FOR OLDER ADUTS AND ARE TRYING TO MAKE TREATMENT DECISIONS IN THIS CONTEXT. AND SO, WE ARE STARTING--THE TRIAL THAT I SHOWED WHERE WE DID COLLECT DATA ON MEDICATIONS AND WE HAVE EARLY CAREER INVESTIGATORS WHO'VE GOTTEN GRANTS TO LOOK AT THAT BUT THERE'S ALMOST NO INFORMATION. WE HAVE MIDDLE INTERACTIONS WITH CERTAIN DRUGS BUT NOT FOR THE O GLOBAL IMPACT OF POLYPHARMACY TREATMENT OUTCOMES. >> OKAY, I THINK THAT TAKES US TO THE END OF OUR TIME. THANK YOU EVERYBODY. >> THANK YOU. I WANT TO EXTEND A THANK YOU TO NIESHES H TO THE TOPIC AREA NUMBER 2. WE WILL TAKE A PAUSE, A 15 MINUTE PAUSE, PLEASE STAND UP. WE WILL RETURN AT 2:45 P.M. EASTERN STANDARD TIME. >> NEXT SLIDE, PLEASE, WE WANT TO ENCOURAGE EVERYONE TO CONTINUE TO SEND IN YOUR FEEDBACK WHO IS WATCHING THIS VIDEOCAST THROUGH THE VIDEOCAST PORTAL. CAN YOU SEE THE SEND LIVE FEEDBACK BUTTON, PLEASE FEEL FREE TO CLICK THAT BUTTON AND SUBMIT ANY COMMENTS OR QUESTIONS THAT YOU MAY HAVE FOR THE PANELS. NEXT SLIDE, PLEASE. MICHELLE HAMSTRA AND DR. STEVEN WALLACE. THANK YOU. >> YOU ARE MUTED STEVEN. SPHRKS STEVEN YOU ARE NOW UNMUTED. >> THANK YOU. >> GREETINGS MY NAME IS STEVEN WALLACE I'M CO-CHAIR OF THE SESSION 3 PANEL OF RECRUITMENT, ENROLLMENT AND RETENTION AND I WILL BREFLY INTRODUCE THE CO SHARE AND THE PANELISTS FOR TODAY AND WE WILL JUST HAND EACH OTHER OFF TO THE NEXT PERSON WHO IS PRESENTING. SO AGAIN I'M STEVEN WALLACE AND I'M PROFESSOR IN THE DEPARTMENT OF HUMAN SCIENCES AT THE UCLA SCHOOL OF PUBLIC HEALTH AND NIA CENTER FOR RESEARCH WHICH HAS A LOT OF CONCENTRATION AND EMPHASIS ON RETENTION AND RECRUITMENT. MY CO-CHAIR TODAY IS MICHELLE HAMSTRA, SIN AN ATY CHILDREN'S MEDICAL CENTER IN THEIR HEART INSTITUTE ASK HAS BEEN THE CHAIR OF THE PEDIATRIC HEART STUDY COORDINATOR'S COMMITTEE SINCE 2011. WE WILL BE COORDINATING THE ORDER OF SPEAKERS IS DIFFERENT THAN WHAT WAS OUR PROGRAM, WE WILL HEAR FIRST FROM MARK SUPIANO WHORKS IS A PROFESSOR AND CHIEF OF THE GERIATRICS DIVISION AT THE UNIVERSITY OF UTAH SCHOOL OF MEDICINE AND HE DIRECTS THE GERIATRIC'S EDUCATION AND CLINICAL CENTER FUNDING ON THE AGING COMMUNITY. ALL OF THESE PANELISTS HAVE LONGER BIOS AS WELL, THEY'RE ALL VERY DISTINGUISHED AND I ENCOURAGE TO YOU GO TO THEIR BIOS. AFTER DR. SUPIANO, WE WILL HAVE DOCTOR RAEGAN DURANT, UNIVERSITY OF ALABAMA AT BIRMINGHAM, DIRECTOR OF MERCY HEALTH SERVICES COMMUNITY AND CENTER ON MINORITY RESEARCH. NEXT WILL BE WENDY KOHRT, PROFESSOR OF MEDICINE AT THE UNIVERSITY OF COLORADO MEDICAL CAMPUS, DIRECTOR OF RESEARCH FOR GERIATRIC MEDICINE THERE AND ASSOCIATE DIRECTOR OF THE COLORADO CLINICAL AND TRANSLATIONAL SCIENCES INSTITUTE AND WRAPPING EVERYTHING UP FOR US WILL BE CONSWALE O WILKINS, DR. WILKIN SYSTEM A GERIATRICIAN AND PRESIDENT OF VANDERBILT UNIVERSITY MEDICAL CENTER AND AS I SAY ALL OF THESE SPEAKERS HAVE MUCH LONGER BY OS AND MANY MORE TIELTSS WE COULD SPEND AN ENTIRE HOUR GOING OVER INSTEAD WE'LL JUST MOVE FORWARD TO OUR PROGRAM. SO NEXT SLIDE. SO THIS IS US, NEXT SLIDE. SO I'M GOING TO GIVE BRIEF COMMENTS ON GERIATRICS PERSPECTIVE, MICHELLE HAMSTRA WILL GIVE A BRIEF OVERVIEW OF PEDIATRIC PERSPECTIVES, I ENCOURAGE YOU TO LOOK, BOTH OF US HAVE PRERECORDED OUR TALK SO MUCH LONGER VERSIONS, NOT EXCESSIVELY LONGER VERSIONS BUT MUCH LONGER OF THESE VERSIONS OF THESE TALKS ARE AVAILABLE ONLINE AND I ENCOURAGE TO YOU LOOK AT THOSE. NEXT. SO JUST AS A REMINDER THIS, IS A FOLLOW UP TO A WORKSHOP THAT HAPPENED IN 2018. AND IN THE SUMMARY OF THAT WORKSHOP, THE LINK WHICH IS BELOW, THERE WAS A GOOD SUMMARY OF A LOT OF THE ISSUES THAT WE'RE TALKING ABOUT TODAY AND SO WE'RE NOT GOING TO REPEAT THOSE AND I'M NOT GOING TO READ THESE EITHER BUT THERE IS A VERY NICE SUMMARY OF ISSUES SPECIFICALLY AROUND RECRUITMENT AND RETENTION AS WELL AS THE OTHER 4 AREAS. THE SUMMARY ALSO INCLUDES A NICE OVERVIEW OF SOME OF THE SOLUTIONS TO THE PROBLEMS THAT PEOPLE FACE. ONCE AGAIN I WON'T GO INTO THOSE IN DETAIL, SOME OF THESE WE WILL REVIEW AGAIN TODAY. NEXT SLIDE. SO FOR TODAY'S SESSION, NOT ONLY ARE WE GOING TO TALK ABOUT GENERAL RECRUITMENT AND RETENTION ISSUES AMONG PEDIATRIC AND GERIATRIC POPULATIONS BUT WE WERE ALSO ASKED TO TRY TO FOCUS ON THE DIVERSITY WITHIN THOSE POPULATIONS. SO WE WILL BE INCLUDE NOTHING OUR DISCUSSION OF RECRUITING AND RETENTION, SOME OF THE SPECIAL ISSUES INCLUDING RACIAL AND ETHNIC DISPARITIES, WOMEN AND GENDER MINORITIES RURAL AND OTHER SUBGROUPS THAT MAY BE INCREASING 3 DIFFICULT TO RECRUIT FOR CLINICAL TRIALS. WITHIN THAT, OUR PANELISTS--PROVIDE CONCRETE EVIDENCE-BASED APPROACHES FROM THEIR OWN CLINICAL PRACTICE AND DURING THEIR OWN EXPERIENCES AND DURING RECRUITMENT AND RETENTION THAT HOPEFULLY WILL BE USEFUL FOR YOU IN THINKING THROUGH SOME OF THESE ISSUES YOU'RE FACING. NEXT SLIDE. SO MY GOAL HERE IS JUST BASICALLY TO REMIND PEOPLE THAT THERE IS DIVERSITY WITHIN THE OLDER ADULTS AND YOUTH POPULATIONS. SO AMONG THE OLDER ADULT POPULATION, IF YOU LOOK AT RACE AND ETHNICITY, YOU WILL NOTICE THE DRAMATIC VARIATION AND 3 GENERATION OWS HOUSEHOLDS SO ADULTS OF COLOR ARE MUCH MORE LIKELY TO LIVE IN MULTIGENERATIONAL HOUSEHOLDS THAT CAN PROVIDE DIFFERENT CHALLENGES BUT ALSO DIFFERENT APPROACHES TO DO RECRUITMENT AND REATTENTION. AS MANY AS 1 OUT OF 5 OLDER ASIAN AMERICANS LIVE IN MULTIGENERATION HOUSEHOLDS, ALMOST 1 OF THE LATIN X HOUSEHOLDS, COMPARED TO ONLY 4% OF THE POPULATION, SO A LARGE VARIATION THERE. IN ADDITION AMONG OLDER ADULTS, EDUCATION AND INCOME LEVELS ARE LOWER, AMONG COMMUNITIES OF COLOR ESPECIALLY IN LATIN X AND BLACK POPULATIONS, WE SECURE ABOUT 2 OUT OF 4. OLDER ADULTS IN LATIN X AND BLACK POPULATIONS ARE LOW INCOME COMPARED TO ABOUT A QUARTER OF OTHER POPULATIONS AND FINALLY THERE'S VERY STRIKING DIFFERENCE IN LIMITED ENGLISH PROFICIENCY AND NEEDLESS TO SAY THAT'S GOING TO BE AN ISSUE WHEN YOU ARE TRYING TO REACH PEOPLE AND ENCOURAGE THEM TO JOIN YOUR CLINICAL TRIAL. SO IF THERE'S A LOT OF DIVERSITY SIMPLY SAYING THAT YOU'RE RECRUITING AGE 65 + DOES NOT MEAN THAT YOU'RE ACTUALLY RECRUITING THE DIVERSITY WITHIN THE POPULATION. NEXT SLIDE. SO, I FOCUS MORE ON THE LATE END OF THE LIFE SPAN BUT ON THE EARLY END OF THE LIFE SPAN, THERE ARE ALSO SIMILAR VARIATIONS BY POPULATION. IF YOU LOOK AT 3 GENERATION HOUSEHOLDS, NOT QUITE AS DARK AMONG OLDER ADULTS BUT YOU STILL HAVE ASIAN LATIN X AND BLACK AS WELL AS AMERICAN INDIAN AND ALASKA NATURES ARE ABOUT TWICE AS LIKELY TO BE IN MULTIGENERATIONAL HOUSEHOLDS FOR CHILDREN. S THEERATES ARE HIGHER THAN IN AIAN POPULATIONS ANDLING WISHIST POPULATIONS MEANING THAT NOBODY IN THE HOUSEHOLD SPEAKS ENGLISH WELL, SO THIS IS NOT SIMPLY THE CHILD OR YOUTH, BUT THIS IS THAT THE ENTIRE HOUSEHOLD IS LIMITED% ENGLISH. SO THESE ARE JUST A COUPLE OF THE VARIATIONS THAT ARE LIKELY TO CREATE SPECIAL CHALLENGES WHEN CONDUCTS RECRUITMENT AND RETENTION IN CLINICAL TRIALS. NEXT. SO WE SAW THIS CHART A LITTLE BIT EARLIER, IT'S THE 5 T FRAHM WORK SPECIFICALLY FOR RECRUITING OLDER ADULTS BUT IN CONVERSATIONS AMONG THIS PANEL WE ALSO CONCURRED THAT MOST OF THE ISSUES ARE SIMILAR AMONG RECRUITING CHILDREN AS WELL. SO IT'S A GOOD FRAMEWORK JUST TO KEEP IN MIND AS YOU'RE MOVING ACROSS AGE POPULATIONS. AND WITH THAT BRIEF ORIENTATION, I AM GOING TO TURN THE MICROPHONE OVER TO MY COLLEAGUE MICHELLE HAMSTRA. >> HI, THANK YOU VERY HAVING ME, I'M EXCITED TO BE HERE AND PART OF THIS PANEL. IT'S BEEN A VERY INFORMATIVE DISCUSSION SO FAR AND I LOOK FORWARD TO SHARING SOME OF MY EXPERIENCE IN RECRUITING AND RETAINING PEDIATRIC POPULATIONS, AS STEVEN SAID, I SPENT MOST OF MY TIME IN THE HEART INSTITUTE RECRUITING PEDIATRICS FOR PARTICIPATION AND RESEARCH RELATED TO CONGENITAL HEART DISEASE. NEXT SLIDE, PLEASE AND ANYONE WHO HAS SPENT TIME IN RECRUITING CHILDREN INTO CLINICAL TRIALS IS WELL AWARE OF THE BARRIERS THAT WE FACE I THINK IMPORTANT IS THE FORMAT OF THIS WORKSHOP AND ADDRESSING SOME OF THE STRATEGIES THAT WE CAN USE TO HELP OVERCOME THOSE CHALLENGES AND BARRIERS. WHILE THEY CAN SEEM OVERWHELMING AT TIMES, I HAVE FELT MOSTLY ENERGIZED BY WORKING WITH MY COLLEAGUES TO FIND WAYS TO OVERCOME THESE BARRIERS AND I THINK MOST IMPORTANTLY IS AS FAR AS STARTING WITH A GOOD TEAM, STARTING WITH A REPRESENTATIVE TEAM THAT'S INCORPORATING PERSPECTIVES FROM VARIOUS STAKEHOLDERS, SO NOT JUST A SCIENTIFIC COMMUNITY BUT ALSO THE COORDINATORS WHO ARE BOOTS ON THE GROUND AND ARE WORKING TO ESTABLISH RELATIONSHIPS WITH THE PARTICIPANT, PARENTS, CAREGIVERS, NOVEMBER NOVEMBER WHAT THE BARRIERS ARE GOING TO BE FROM THAT POPULATION, ARE YOU POOLING FROM THE TYPICAL AREA OR DO YOU HAVE TO REACH FURTHER WHICH IS OFTEN THE CASE FOR US WITHIN THE CONGENITAL HEART WORLD. WE DON'T SEE ENOUGH PATIENTS AT ANY 1 CENTER TO BE ABLE TO HAVE MEANINGFUL NUMBERS SO WE HAVE TO LOOK OUTSIDE OF OUR TYPICAL CATCH AREA. AS YOU'RE WORKING TO DEAL WITH THESE BIRXIERS IERS--BARRIERS IT'S IMPORTANT THAT YOU ADDRESS THE BUDGET AND LOOK AT IT WISELY AND LOOK AT NOT JUST THE COST TO STUDY PROCEDURES BUT WHAT INFRASTRUCTURE WILL YOU HAVE TO PUT IN PLACE TO HELP ACCOMMODATE THE PARTICPANTS THAT ARE COMING FOR THE CENTER FOR THE RESEARCH. ONCE YOU HAVE YOUR PLAN, RECRUITMENT AND RETENTION PLAN DRAFTED AND WRITTEN INTO THE PROTOCOL OF OPERATIONS AND YOU'RE READY TO START ENROLLING AND IMPLEMENTING THE PLAN, IT'S IMPORTANT TO PAUSE AT REGULAR INTERVALS AND EVALUATE HOW THINGS ARE GOING AND AS WAS MENTIONED BEFORE IT'S AN ITERATIVE PROCESS SO YOU NEED TO CONSTANTLY EVALUATE TOOLS AND STRATEGIES YOU'RE USING AND HOW EFFECTIVE THOSE ARE AT REACHING THE POPULATION AND HAVING THAT CONSTANT COMMUNICATION WITH A CARE TEAM WITH A PARTICIPANTS AND FIGURING OUT WHY IT MAY BE DIFFICULT TO RECRUIT INTO THE POPULATION AND AS SEFENNISTERATION SAID THE 5 T FRAMEWORK WHICH MAY HAVE BEEN DEVELOPED WITH THE GERIATRIC POPULATION IN MIND, I THINK IT'S VERY RELEVANT TO THE WORK WE'RE DOING ON THE PEDIATRIC SIDE AS WELL IDENTIFYING THE TARGET POPULATION, DEVELOPING A ROBUST TEAM, MAKING SURE YOU HAVE ADEQUATE TIME AND TOOLS AND TECHNOLOGY IN ORDER TO REACH YOUR GOALS. NEXT SLIDE, PLEASE. AND SO I WANT TO ALSO BRING SOME REAL WORLD EXAMPLES WITH SOME OF THE STUDIES WE'VE WORKED ON IN THE PAST, 1 OF WHICH IS THE [INDISCERNIBLE] TRIAL AND BARRIERS WE FACED WHEN WORKING IN THIS STUDY, IT WAS A RARE DISEASE THAT HAD A LOT OF INCLUSION AND EXCLUSION CRITERIA IT WAS A COMPLEX DRUG STUDY WITH MULTIPLE PERSON VISITS AND MEDICATION REGIMEN OVER 3 YEARS. ALL THAT SAID, WE WERE ABLE TO MEET AND EXCEED OUR TARGET OF PARTICIPANTS, THEY RANGED IN AGE FROM 6 MONTHS TO 24 YEARS THROUGH THE COURSE OF THE STUDY, WE HAD EXCELLENT RETENTION WITH 88% ACHIEVING THE PRIMARY OUTCOME MEASURE. AFTER THE STUDY HAD COMPLETED AND THE MAIN RESULTS WERE PUBLISHED WE TOOK TIME TO GO BACK AND LOOK AT SOME OF THE LESSONS THAT WE LEARNED ALONG THE WAY. WHILE WE DID MEET AND EXCEED OUR ENROLLMENT TARGET IT TOOK MORE TIENL THAN WE THOUGHT AND I THINK IT TOOK MORE RESOURCES AND TIME THAN WE ANTICIPATED SO THE DURATION OF ENROLLMENT WAS EXTENDED BY A YEAR, I BELIEVE SCH THEN WE ALSO WANTED TO LOOK AT THE STRATEGIES WE USED FOR RECRUITMENT AND RETENTION BECAUSE WE FELT WE WERE OVERALL SUCCESSFUL AND WE WANTED TO LOOK AT HOW GOOD OUR ADHERENCE WITH WITH THE PROTOCOL AND ALSO WITH MEDICATION AND WE TRIED TO SEE WHAT FACTORS WERE INFLUENCING AND PREDICTING BETTER ADHERENCE. SO SOME OF THE LESSONS WE LEARNED IS NUMBER 1, IT TAKES A WIDE VARIETY OF STRATEGIES FOR RECRUITMENT AND RETENTION AND ADHERENCE TO BE SUCCESSFUL. IT'S NOT A ONE-SIZE-FITS-ALL BLANKET THAT YOU CAN REACH OUTED, THE BROADER YOUR PLAN IS, THE MORE LIKELY YOU ARE TO REACH THE VARIOUS PATIENT POPULATION AND DEMOGRAPHICS. WE FOUND THAT YOUNGER AGE WAS ASSOCIATED WITH SLIGHTLY BETTER ADHERENCE, THE YOUNG ADULTS AND ADOLESCENTS HAD THE LOWER LEVELS OF ADHERENCE WHEN WE LOOK AT IT ACROSS 24-MONTHS TO 26 YEARS. AND THAT'S NOT SURPRISING, WITH AGE COMES MORE COMPLEXITIES, YOU'RE LOOKING AT MORE RIGOROUS SCHOOLING, JOBS, SPORTS, ACTIVITIES OUTSIDE OF THE HOUSE, OR OUTSIDE OF THE SCHOOL, AND IT TAKES MORE LOGISTICS IN ORDER TO HAVE THE ADHERENCE WHEREAS SOME OF THE YOUNGER PARTICIPANTS HAD MORE SUPPORT WITH PARENTS IN TERMS OF GETTING THEM TO THEIR APPOINTMENTS AND HAVING THEM TAKE THEIR MEDICATION. WE ALSO NOTED SOME RACIAL DIFFERENCES IN THAT THE AFRICAN AMERICANS ADHERENCE TO THE PROTOCOL AND WE WEREN'T ABLE TO REALLY UNDERSTAND THAT BUT TOOK TOO IT THAT WE MAY NEED TO LOOK AT WHAT WE'RE DOING TO SUPPORT THE VARIOUS DEMOGRAPHICS WITHIN THE STUDY POPULATION. --AND THAT'S NOT SURPRISING BUT WHAT WE DID STRESS WAS THE IMPORTANCE OF THE LABRATIVE LEARNING. SO CREATING A FORMAT TO WHERE YOU COULD HAVE SHARED DISCUSSION AND OPEN DISCUSSIONS ABOUT WHAT WAS WORKING AT THE SITES WHO WERE HAVING SOME SUCCESS IN TERMS OF BEING ABLE TO BRING PARTICIPANTS IN FROM A RURAL AREA OR ACHIEVING BETTER BOTTLE RATE RETURN AND WHAT NOT SO THE IMPORTANCE OF COLLABORATIVE LEARNING WAS NOT TO BE MINIMIZED AS WELL AS 1 OF THE CRITICAL PIECES OF SUCCESS FOR OUR STUDY WAS WE'RE PARTNERING WITH A PATIENT ADVOCACY GROUP. WE WORKED WITH THE MARFAN FOUNDATION AND THEY WERE ABLE TO PROPOSED PROVIDE SUPPORT IN REACHING THE POPULATION, THEY HELPED US ESTABLISH TRUST WITH THEM, INFORMATION ABOUT THE STUDY, GET INFORMATION ON THEIR WEBSITE AND AT IN-PERSON MEETINGS AND BRING STUDY INVESTIGATORS TO THOSE MEETINGS TO TALK ABOUT THE STUDY, AND ESTABLISH THE TRUST AND THEY ALSO PROVIDED SUPPORT WITHIN THE STUDY. WE HAD SOCIAL SERVICE WORKER AND [INDISCERNIBLE] ON THE STUDY COMMITTEE CALLS AND WE WERE ABLE TO TALK TO FAMILIES AND PROVIDE THESE RESOURCES FOR FAMILIES TO OVERCOME BARRIERS IN TERMS OF TRAVEL, PROVIDING EMERGENCY AIR LIFT FOR PATIENTS FROM REMOTE AREAS OR COMPENSATION OR REEMBURSEMENT FOR MILES OR PAIN FOR ECHO CARDIO GRAMS THAT THEY WERE COVERED BY THE INSURANCE ON THE RESEARCH BUDGET. SO WE TOOK THOSE LESSONS THAT WE LEARNED AND WE REACHED SUCCESS AND IT TOOK A LOT OF EFFORT. SO WE WANTED TO CARE THOSE LESSONS FORWARD. SO MOVING ON TO THE [INDISCERNIBLE] TRIALS THEY CAME AFTER THE MARFAN TRIAL AND WE TRIED TO AGAIN USE WHATLY LEARNED TO MAKE THIS STUDY A SUCCESS. THIS WAS A PHASE 3 RANDOMIZED CONTROL TRIAL WITH A 6 MONTH THERAPEUTIC REGIMEN OF [INDISCERNIBLE] VERSE US PLACEBO AND ADOLESCENTS AND OUR GOAL WAS 400 ADOLESCENTS BETWEEN 12 AND 18 YEARS AND LEARNING FROM OUR PREVIOUS WORK WE PARTNERED WITH AN INDUSTRY PARTNER NECKSIUM PHARMACEUTICAL TO HELP SUPPORT FINANCES AS WELL AS PATIENT ADVOCACY GROUP AND WE WERE ABLE TO MEET OUR PROTOCOL WITH THE HELP OF 30 SITES AND 3 COUNTRIES AND THE PATIENT ADVOCACY GROUP HELPED US AS WE DESIGN THE STUDY MAKING SURE IT WILL BE FEASIBLE STRESSING THE IMPORTANCE OF HAVING TRAVEL FUNDS IN ORDER TO GET PARTICIPANTS TO THE MEDICAL SITES AND LIMITED PARTNERSHIPPING FROM THE MARFAN TRIAL WHERE THE ADOLESCENTS STRUGGLED SOMEWHAT IN TERMS OF ADHERENCE, WE PROVIDED THEM WITH iPAD,--iPOD TO HELP WITH PROGRAMMING OF MEDICATION REMINDERS, STUDY VISITS AND COMMUNICATION IN TERMS OF ADVERSE EVENTS. AND WE MADE SURE THAT WE HAD A ROBUST COMPENSATION PLAN, WE WORKED WITH THE PATIENT ADVOCACY GROUP IN THE EARLY PHASES OF THE DESIGN AND WERE ABLE TO MODIFY THE PROTOCOL TO MAKE A COUPLE OF IN BETWEEN VISITS VIRTUAL OR HAVE NURSING VISITS TO THE HOME. AND 1 OF THE KEY SUCCESSES WAS 1 WE HAD COMPLETED THE STUDY AND READY TO SHARE THE INFORMATION WITH THE COMMUNITY, WE CREATED A WEBEX IN TERMS TO BE ABLE TO SHARE THE RESULTS OF THE STUDY, ALMOST IN REALTIME WITH THE PATIENT AND THE FAMILIES THEMSELVES. AND FROM THEIR WE WENT ON TO THE FUEL OLE, WHICH WAS AN OPEN LABEL SAFETY EXTENSION AND IT WAS PROVIDED ACCESS AND CONTINUED SAFETY DATA FOR UP TO 36 MONTHS AFTER THE COMPLETION OF THE FUEL TRIAL, IT WAS THE SAME PATIENT POPULATION THERE BUT ENROLLED INTO FUEL OLE AND IF WE DIDN'T HAVE 300 ADOLESCENTS WAS THE GOAL, THAT WAS ROLLED OVER WE WERE ABLE TO OPEN IT UP TO DE NOVO PATIENTS WITH THE SAME INCLUSION AND EXCLUSION CRITERIA. SO IT WAS AN EXAMPLE OF BEING ABLE TO LEARN FROM OUR SUCCESSES AND THE IMPORTANCE OF HAVING PARTNERS IN THE PROCESS TO SUPPORT THE RECRUITMENT AND RETENTION. NEXT SLIDE, PLEASE. SO THEN WE MOVED TO OBESITY AND INTERVENTION AND TEENS TO DO THE TRIAL, PURPOSE OF THE STUDY WAS TO SEE IF OBESITY AND LIPIDEMIA, WILL IMPROVE MEASURES FOR ATHEROSCLEROSIS WITH ACCEPTABLE SAFETY. AS OF AUGUST, THE END OF AUGUST WE HAD 148 CONSENTED, 91 RANDOMIZED. THE STUDY LAUNCHED AROUND THE SUMMER OF 2018 SO THIS IS A STUDY WHERE WE ARE SOMEWHAT STRUGGLING IN TERMS OF REACHING OUR ENROLLMENT TARGETS. THE CHALLENGES WE FACE IS THAT THIS IS A PREVENTATIVE COHORT THAT FEELS WELL, IT REQUIRES MULTIPLE IN-PERSON VISITS ALL OF WHICH INCLUDE BLOOD DRAWS, MEDICATION FOR 2 YEARS. SOME OF THE STRATEGIES THAT WE'VE USED TO MEET THESE CHALLENGES, WE IMU FROM THE BEGINNING THIS WAS GOING TO BE A CHALLENGING STUDY FOR RECRUITMENT AND RETENTION SO WE WOULD TRY TO ESTABLISH A COMPREHENSIVE PLAN, PAYING SPECIAL ATTENTION TO COMPENSATION INCENTIVES AND PARTNERING WITH THE CARE PROVIDERS AND THE FACAS AMLYS. ONE OF THE INCENTIVES THEY GET WHEN WITH A FIT BIT THAT HELPS PHYSICAL ACTIVITIES. IT'S REQUIRED US TO GO BACK AND REVISE OUR PLAN, WE'VE HAD A FEW PROTOCOL AMENDMENTS, WE'VE EXTENDED THE DURATION OF RECRUITMENT, TRIED TO STREAMLINE, SCHEDULE MEASUREMENT, WE HAD TO GO BACK AND LOOK AT THE INCLUSION, EXCLUSION CRITERIA, WHAT WE COULD DO TO MAKE IT MORE INCLUSIVE. WE EXPANDED THE AGE, WE BROUGHT INTO THE BMI REQUIREMENTS AND WE WERE ABLE TO ELIMINATE 2 OF THE IN-PERSON VISITS. SO WE'RE GETTING THERE. IT'S A WORK IN PROGRESS, IT GOES BACK TO MAKING SURE THAT YOU HAVE THE RIGHT TOOLS, RIGHT TEAM, THE RIGHT RESOURCES AND THAT YOU'RE ABLE TO DEVOTE THE AMOUNT OF TIME BECAUSE IT'S ALL WORTH IT TO MAKE SURE THAT WE CAN HAVE MEANINGFUL RESULTS TO IMPROVE OUTCOMES. SO, WITH THAT I'M GOING TO HAND IT OVER, NEXT SLIDE ARE SOME REFERENCES. HAND IT OVER TO MARK AS HE LISTS OUT SOME OF THE COMPARISONS AND DIFFERENCES IN RECRUITING ACROSS THE LIFESPAN. THANK YOU. ARE OTHERS ABLE TO HEAR MARK? >> I AM NOT. >> NO. >> MARK YOU'VE BEEN UNMUTED, CAN YOU SAY ANYTHING? OKAY, WE'LL TAKE A PAUSE HERE, WE WILL ACTUALLY MOVE TO--IF THE PERSON CAN MOVE THE SLIDE NUMBER 180, AND WE WILL ALLOW RAEGAN DURANT TO PRECEPT AND THEN WE WILL WORK ON AUDIO FOR MARK SUPIAN O. >> GOOD AFTERNOON EVERYONE. SO I WILL FOCUS A LITTLE BIT ON LIFE SPAN LESSONS AND TRY TO THINK ABOUT OR SPARK SOME THOUGHT ABOUT SOME LESSONS THAT WE CAN LEARN FROM ENROLLMENT OF PEDIATRIC POPULATIONS PARTICULARLY ON THE CONTEXT OF ONCOLOGY TRIALS AND APPLY THEM IN OLDER ADULT POPULATIONS, NEXT SLIDE. SO THE CANCER WORLD AMONG CHILDREN IS 1 BRIGHT SPOT IN THE ENROLLMENT OF PEDIATRIC POPULATIONS. AS YOU CAN SEE ON THE LEFT HAND SLIDE HERE DEPENDING ON WHICH STUDY OR WHICH CONTEXT, YOU LOOK AT, ROUGHLY 27-86% OF OF CHILDREN WITH CANCER ARE ENROLLED IN CLINICAL TRIALS AND THIS IS A STARK CONTRAST WHEN WE LOOK AT ADULT CANCER POPULATIONS WHERE THOSE PERCENTAGES ARE MUCH LOWER AND THE ESTIMATES ANYWHERE FROM 1.5 TO 4% OF ADULTS WITH CANCER ENROLLED IN TRIALS. AND THE GRAPH AT THE LEFT PREDICTS THE MISMATCH WE SOMETIMES SEE BETWEEN THE REFULENCE OF CANCER IN OLDER ADULTS ARE PREPARED TO ENROLLMENT TRIALS AND ONCOLOGY--SESSIONS BUT THE LIGHTER COLORED BARS REPRESENT TD PORTION OF THE U.S. CANCER POPULATION AT VARYING AGE GROUPS, SO THE LEFT MOST GROUP ARE THOSE 65 OR OLDER. YOU CAN SEE THAT LIGHT COLORED BAR REPRESENTING THE PERCENTAGE OF FOLKS 65 OR OLDER WITH CANCER IS ABOUT TWICE AS LARGE AS THE DARKER COLORED BAR WHICH REPRESENTS THE PERCENTAGE OF THOSE PATIENTS AND PERCENTAGE OF ELDERLY PATIENTS COMPRISING TRIAL POPULATIONS IN CANCER AND THEN YOU CAN SEE WITH EACH INCREASING INCREMENT BUT IN TERMS OF CUT OFF OF AGE, 65 OR OLDER, 75 ON THE FAR RIGHT, THE POETIC PORTION REPRESENTED IN UNITED STATES CANCER POPULATION IS GETTING SMALLER BUT WHEN'S GETTING SMALLER EVEN DIMINISHING MORE SIGNIFICANTLY IS THE PROPORTION REPRESENTED IN TRIALS. SO CAN YOU SEE IN THAT LAST GROUP IT'S NOT EVEN A THIRD OF PERSONS 75 OR OLDER REPRESENTED IN TRIALS SO AGAIN A MISMATCH HERE BETWEEN THE PREVALENCE IN OLDER AGE AND THE REPRESENTATION IN TRIALS. NEXT SLIDE. SO IN THE CHILDREN'S ONCOLOGY GROUP WHICH IS A NATIONAL NETWORK OF COORDINATED NETWORK OF TRIALS REPRESENTS ROUGHLY 200 INSTITUTIONS FORMED FIRST IN 2000 WHICH REALLY MEANT TO CREATE FOR THE PEDIATRIC POPULATION MANY OF THE CORPRATIVE ONCOLOGY GROUPS THAT EXIST FOR ADULTS. ROUGHLY 19% OF U.S. CANCER PATIENTS AGE 0-19 ARE ENROLLED IN A CHILDREN'S ONCOLOGY GROUP TRIAL AND THAT'S QUITE AN ASTOUNDING FIGURE WHEN YOU THINK THAT ALMOST 20% OF CANCER PATIENTS IN THAT AGE RANGE ARE ENROLL INDEED 1 OF THESE NETWORK STUDIES AND UNFORTUNATELY THAT HIGH PERCENTAGE IS NOT UNIFORM OVER THE TOTALITY OF CHILDHOOD ADLEASENTS IN YOUNG ADULTHOOD, YOU SEE IT'S TWEIVE% SO EVEN HIGHER WHEN YOU CONSIDER THE YOUNGER STAGES, 0-9, DROPS TO 12.8% WHEN LOOKING AT THOSE THAT ARE PRETEEN AND ADOLESCENT, 10-19 YEARS AND THEN DROPS OFF DRAMATICALLY WHEN WE LOOK AT YOUNG ADULTS 20-29 YEARS. AND THE DEMOGRAPHIC DISTRIBUTIONS IN THESE--IN THESE CHILDREN'S ONCOLOGY GROUP TRIALS ARE ACTUALLY EQUAL DISTRIBUTION BY GENDER WHICH IS I THINK WE NEATED EARLIER WE HAVE NOT ALWAYS SEEN IN ADULT TRIALS, PARTICULARLY AMONG OLDER ADUTS AND IT'S LARGELY PROPORTIONATE TO THE REPRESENTATION AMONG CANCER CASES IN CHILDREN HERE IN THE U.S., AGAIN, NOT SOMETHING WE ALWAYS SEE AMONG ADULTS AND THEN SOCIOECONOMIC FACTORS ARE ALSO EQUALLY DISTRIBUTED AMONG AGE GROUPS SO AGAIN THE DEMOGRAPHIC DISTRIBUTIONS ARE FAIRLY REPRESENTATIVE OF WHAT WE SEE IN THIS GROUP AMONG CANCER CASES, AMONG CHILDREN. NEXT SLIDE. AND SO, IN THIS SLIDE, I WANTED TO TAKE A LOOK AT SOME OF THE FACTORS INFLUENCING ENROLLMENT IN CANCER CLINICAL TRIALS, AT BOTH ENDS OF THE LIFE SPAN. SO STATUS IN THE FIRST ROW, THE LOWER RATES OF INSURANCE AMONG YOUNGER CHILDREN, THOSE CHILDREN WHO ARE GROWING UP IN HOUSEHOLDS LIVING BELOW THE POVERTY LINE, OFTEN TIMES HAVE ACCESS TO MEDICAID AND IN ADULTS THERE ARE ALSO LOWER RATES OF INSURANCE RELATIVE TO THE POPULAR GENERATION AS MOST OLDER ADUTS ARE MEDICARE ELIGIBLE. AND WE LOOK AT SOURCE OF CARE, WE DO SEE DIVERGENCE HERE, 90% OF CHILDREN UNDER THE AGE OF 15 DIAGNOSED WITH CANCER AND TREATED AT NCI AT SPONSORED INSTITUTIONS. JUST THE OPPOSITE IS TRUE IT IN ELDERLY ADUTS AND MOST ADULTS IN GENERAL, MOST OF THE CANCER CARE RECEIVED BY BY COMMUNITY ONCOLOGIST AND NOT AT NCI SPONSORED INSTITUTIONS, THE ENGAGEMENT OF OTHERS IN RECRUITMENT, THE RECRUITMENT AMONG--PARTICULAR ATTENTION TO THIS IN SOME SUBGROUPS RACIAL AND ETHNIC MINORITIES, ENGLISH PROFICIENCY AND INCOME STATUS, THERE MAY EVEN BE HIGHER PROPORTIONS OF PERSONS LIVING IN MULTIGENERATIONAL HOUSEHOLDS THAT ALSO SUGGEST THERE IS ARE CAREGIVERS MORE LIKE LIE INVOLVED AND THEN TUMOR TYPE. THERE ARE MANY TUMOR TYPES THAT ARE FAR MORE PREVALENT IN CHILDREN AND MANY OF THE TRIALS THAT ARE LAUNCHED MAY EXCLUSIVELY BE AIMED AT PEDIATRIC POPULATIONS AND LEUKEMIA OR A. L. L. SPECIFICALLY COME TO MIND, NEUROBLASTOMA ALSO, AMONG ADULTS THE SAME SORT OF PREVALENCE, EXCLUSIVE PREVALENCE IN 1 AGE GROUP DOESN'T QUITE EXIST THOUGH MANY CANCERS ARE MORE COMMON AMONG OLDER ADUTS OFTEN TIMES THESE DIAGNOSIS ARE NOT EXCLUSIVE TO OLDER ADULTS OR AS EXCLUSIVE AS SOME DIAGNOSIS IN PEDIATRIC POPULATIONS. NEXT SLIDE. SO WHAT ARE SOME OF THE TAKE HOME MESSAGES METAPHORICALLY THIS, IS SORT OF A US SORT OF TRYING TO LEARN MORE ABOUT THE ELDERLY FROM THE YOUNG AND 1 OF THE WAYS IS EXPANDING TRIAL ACCESS TO THE ELDERLY IN 2 WAYS SO AGAIN, I MENTIONED THAT 90% OF THE U.S. PEDIATRIC CANCER PATIENTS RECEIVED SPONSORED IN INSTITUTIONS AND THE SAME IS TRUE IN OLDER ADUTS, WE CAN DEDICATE THIS AT CARE TO OLDER ADUTS OBVIOUSLY THERE'S NOT ENOUGH CAPACITY TO CARE FOR ALL OLDER ADULTS WITH CANCER IN THESE CENTERS, BUT WE CAN INCREASE ACCESS TO SOME EXTENT. I THINK THE SECOND BULLET REPRESENTS THE FAR MORE FRUITFUL WAY TO EXPAND ACCESS AND THAT REALLY IS EXPANDING IT TO COMMUNITY BASED CENTERS AND COMMUNITY-BASED PRIMARY CARE GERIATRIC PRACTICES. SO THIS GAZ FAR GROUND THE EASIEST WAY TO DO THAT AND THAT IS TO EXPAND RECRUITMENT SO WHAT I MEAN IS A MODEL IN WHICH YOU SPAN RECRUITMENT TO THESE COMMUNITY BASED CENTERS BUT THEN ALL THE RESEARCH ACTIVITIES WOULD TAKE PLACE AT THESE MORE RESEARCH INTENSE SITES OF CARE, MANY OF WHICH OFTEN TIMES ARE ACADEMIC SITES. SO IT GOES BEYOND THAT. HAD INSTEAD IT ACTUALLY MEANS EXPANDING OR EXTENDING SOME OF THE RESEARCH ACTIVITIES TO THESE COMMUNITY BASED SITES. NOW, SOMETIMES THAT MAY BE FINANCIAL PROHIBITIVE OR LOGISTICALLY NOT FEASIBLE BUT THERE MAY BE SPL WAYS IN WHICH THIS CAN BE DONE QUITE SAISMLY. SO IF THERE ARE RESEARCH VISITS THAT REQUIRE EXAMS OR LAB ONLY OR BASIC IMAGING STUDIES, THOSE ARE THE TYPES OF ACTIVITIES THAT COULD BE EXPANDED TO THESE SITES AND ALLOW PEOPLE TO PARTICIPATE IN RESEARCH IN THE SAME PLACES WHERE THEY RECEIVE CARE AND OFTEN TIMES, THIS IS GEOGRAPHICALLY MORE ACCESSIBLE TO THEM, I THINK THERE CAN BE A FOCUS ON FAMILY BASED RECRUITMENT TO ENGAGE CAREGIVERS WHEN WE'RE THINK BEING OLDER ADULTS, WE--IT'S BEEN DISCUSSED EARLY THEY'RE OFTEN TIME IT IS OLDER ADULTS ARE PARTICULARLY--WE THINK ABOUT RACIAL EXPW ETHNIC MINORITIES THAT ARE NOT OFFERED, PARTICIPATION OPPORTUNITIES IN TRIALS AND WHEN THEY ARE IT PROBABLY IS HELPFUL TO TRY TO ENGAGE A CAREGIVER OR SOME OTHER LOVED 1 WHO CAN HELP IN THE DECISION MAKING AND TO THE EXTENT THAT THE NOTION MAY SEEM OVERWHELMING TO AN ELDERLY ADULT, THERE MAY BE AN ADDITIONAL PERSON WHOM THEY TRUST THAT CAN BE ENGAGED AS WELL TOWARD HELPING THEM TO MAKE AN INFORMED DECISION ABOUT TRIAL PARTICIPATION. WE ALSO NEED TO CLARIFY PAYMENT AND COVERAGE CONSIDERATIONS IN ORDER TO OPTIMIZE ENROLLMENT AND WHAT IS LARGELY INSURED POPULATION. SO, REALLY CLARIFYING FOR FOLKS WHO HAVE MEDICARE, WHAT'S COVERED, WHAT'S NOT, AND IF THERE ARE ANY MISGIVINGS ABOUT WHETHER OR NOT THERE WILL BE SOME FINANCIAL PENALTY ABOUT PARTICIPATING, PEOPLE ARE CLEAR ABOUT THAT UP FRONT AND HOPEFULLY GIVEN THE FACT THAT MEDICARE WILL COVER STANDARD CARE EVEN IF IT'S PROVIDED IN THE CONTEXT OF A TRIAL, HOPEFULLY THIS CAN REASSURE SOME FOLKS AND PARTICULARLY HELP TO EQUALIZE IT----THAT'S BEEN DISCUSSED PREVIOUSLY AND ALSO WITH REGUARD TO FUNDING AND FUNDING AGENCIES, NOT JUST NIH BUT ALSO INDUSTRY AND OTHER SOURCES OF FUNDING REALLY MANDATING AND ENFORCING ROLES ABOUT INCLUDING THE ELDERLY AND THEN TRIAL NETWORKS. SO TO THE EXTENT THAT SO MANY OF THE PATIENTS THAT ARE RECRUITED FOR CLINICAL STUDIES, TRIAL NETWORKS OR REG INDUSTRIES INSURING THAT THOSE ORGANIZES ARE STRUCTURE INDEED A WAY TO INSURE THAT OLDER ADULTS ARE ENCLOUDED AND THERE IS A POOL OR SAMPLE POPULATION OF OLDER ADULTS TO CHOOSE FROM TO MAKE SURE THAT THEY'RE ADEQUATELY REPRESENTED SO WITH THEY WILL TURN IT OVER TO THE NEXT SPEAKER. THANK YOU. >> SO THANK YOU DR. DUR ABT FOR YOUR FLEXIBILITY, I WILL START OVER, ARE YOU ABLE TO HEAR ME NOW? ALL RIGHT, THANK YOU I APOLOGIZE FOR THE TECHNICAL PROBLEMS IF I COULD HAVE THE NEXT SLIDE. SO, AS INTRODUCED I'M A GERIATRICIAN BUT 1 OF THE THINGS THAT I LEARNED THAT WE DISCUSSED AMONGST OUR PANEL AND FOLLOWING UP FROM DR. DURANT'S LAST SLIDE, I WANTED TO BEGIN BY SHARING THAT THERE ARE MORE SIMILARITIES AND DIFFERENCES THAT AT OPPOSITE ENDS OF THE LIFE SPAN BUT TO BEGIN WITH THAT MEASURES OF FUNCTION AND COGNITION SUPERSEDE CHRONOLOGICAL AGE. SO IT'S NOT SUFFICIENT JUST TO REPORT YOUR AGE OF YOUR PARTICIPANTS BUT REALLY TO BE ABLE TO IDENTIFY THESE IMPORTANT PHENOTYPES OF INDIVIDUALS AT OPPOSITE ENDS OF THE LIFESPAN. SECONDLY TO FOLLOW FROM THAT, TO INCLUDE OUTCOME MEASURES TO MATTER TO PARTICIPANTS. THRDLY, THAT INDIVIDUALS AT OPPOSITE ENDS OF THE LIFE SPAN ARE POTENTIALLY VULNERABLE INDIVIDUALS, MAKING IT ALL THE MORE IMPORTANT TO WEIGH PARTICIPANT BURDEN IN EFFORTS OF STUDY DESIGN AS WELL AS IN RECRUITMENT AND RETENTION. NEXT, OPPOSITE ENDS OF THE LIFE SPAN MAY OFTEN BE DEALING NOT WITH THE PARTICIPANT BUT WITH THE PARTICIPANT'S PARENT OR THEIR SPOUSE OR CHILD AND THERE'S OFTEN A NEED FOR A PROXY RESPONDENT AND/OR CAREGIVER INVOLVEMENT TO BE ACTIVE LOAMACYY INVOLVED IN THE COURSE OF THE TRIAL PARTICULARLY FROM THE STANDPOINT OF RETENTION. ON THE FRONT END THOUGH, THIS MAY NEED TO INCLUDE OTHERS IN THE CONSENT PROCESS OR IN COMMUNICATION AND HAVING A POINT OF CONTACT, IF THE PARTICIPANT HER OR HIMSELF IS NOT ABLE TO PROVIDE THAT INITIAL POINT OF CONTACT AND LIKEWISE FOR TRANSPORTATION NEEDS IF THE PARTICIPANT NEEDS TO RELY ON SOMEONE ELSE A CAREGIVER FOR THEIR PRANS PORTATION THAT WILL OF COURSE IMPACT RETENTION IN THE TRIAL AND THEIR ADHERENCE. NEXT, IT'S IMPORTANT TO FACTOR THAT STUDY VISITS MAY REQUIRE MORE TIME AND SPECIAL ACCOMMODATIONS, SOME OF THESE MAY INCLUDE SITE ACCESSIBILITY AND FOLLOWING FROM THAT IT MAY BE NECESSARY TO CONSIDER IN-HOME ASSESSMENTS OR TODAY IN THE COVID ERA CONVERTING TO VIRTUAL VISITS IF NECESSARY. AND THEN FINALLY, AT OPPOSITE ENDS OF THE LIFE SPAN NECESSITY TO PLAN AT ALL STAGES FOR POTENTIAL HIGHER ATTRITION RATE TO BUILD THAT INTO THE DESIGN AND THE BUDGET FOR THE TRIAL. SO IN MY REMAINING TIME I WILL TALK ABOUT 2 EXAMPLES OF CLINICAL TRIALS I HAVE BEEN INVOLVED WITH. IF I COULD GO TO THE NEXT SLIDE, PLEASE. THE FIRST IS THE SIS TOLL-LIKE RECEPTORIC BLOOD PRESSURE INTERVENTION TRIAL OR SPRINT AND THE SUBTITLE FOR THIS SLIDE IS THAT IT CAN BE DONE. AND THE EXPERIENCE FROM SPRINT HAS BEEN THAT IT DEMONSTRATE THAD A DIVERSE AND PARTICULARLY OLDER POPULATION CAN BE RECRUITED, RANDOMIZED AND ASSESSED FOR FOLLOW UP INCLAUDING CO COGNITIVE FUNCTION OVER MORE THAN 5 YEARS OF FOLLOW UP WITH VERY SUCCESSFUL RETENTION AND ADHERENCE OUTCOMES. SO SPRINT EXCEEDED ITS RECRUITMENT GOAL WITH 9361 PARTICIPANTS. ALSO MET THE SUBGHOULS, 28% WERE OVER THE AGE OF 75 OF WHOM A QUARTER WHO BLACK OR HISPANIC OF THE GROUP 75 AND OLDER 1 GROUP MET CRITERIA FOR BEING FRAIL AND HAD AN AVERAGE SCORE ON A SCREENING--AND WE'RE STILL NONETHELESS ABLE TO BE RECRUITED AND RETAINED IN THE TRIAL. IT WAS IDENTIFIED THAT TARGETED NAMELY AGE AND ZIP CODE MASS MAILINGS PROVIDED THE GREATEST YIELD FOR RECRUITMENT PURPOSES. BECAUSE OF THE INCLUSION OF OUTCOMES OF FRAILTY, THE OUTCOMES FOR THE TRIAL, THE CARDIOVASCULAR MORTALITY OUTCOMES WERE ABLE TO BE SEGREGATED BY FRAILTY AND GAIT SPEED WHICH ADDED A LOT OF IMPACT FROM THE RESULT FROM SPRINT. IN ADDITION SPRINT FROM THE VERY BEGINNING WAS DESIGNED TO INCLUDE COGNITIVE IMPAIRMENT OUTCOMES AND THE MILD COGNITIVE IMPAIRMENT AND DEMENTIA OUTCOMES WERE REPORTED IN THE SPRINT MIND RESULTS OVER A YEAR AGO AND IF THERE'S TIME IN THE QUESTIONS I CAN STRIEB THAT SPRINT MIND IS ACTUALLY ONGOING THANKS TO ADDITIONAL SUPPORT FROM NIA. SO WITH ALL THESE STRENGTHS FROM SPRINT, THERE ARE STILL SOME LIMITATIONS AND I WILL JUST POINT OUT THAT THERE ARE STILL LIMITATIONS TO IT'S GENERALIZABILITY IN THAT EXCLUSION CRITERIA, INCLUDED PEOPLE WITH BASE LINE DEMENTIA OR WHO WERE RESIDING IN HUSBANDERRING HOMES AT THE TIME OF RANDOMIZATION. SO THAT'S THE EXPERIENCE WE HAD WITH MYSELF AND COLLEAGUES IN SPRINT. IT'S DEMONSTRATING THIS CAN BE DONE DESPITE IT SEEMS SOMEWHAT DAUNTING. THE NEXT SLIDE, PLEASE. I WILL MOVE TO A TRIAL THAT IS JUST GETTING STARTED AND THE SUBTITLE FOR THIS SLIDE IS WE EXPECT IT CAN BE DONE AND HOPE IT CAN BE DONE. SO THE RECRUITMENT INTO THE PRAGMATIC EVALUATION OF EVENTS AND BENEFITS OF LIPID LOWERING IN OLDER ADUTS OTHERWISE KNOWN AS PREVENTIBLE, BEGAN YESTERDAY, SO THIS IS A PRAGMATIC TRIAL THAT THOSE OF US IN THE GERIATRIC UNIVERSE ARE CELEBRATING AND REALLY WANT TO THANK AND HIGHLIGHT THE LEADERSHIP FROM NIA FOR SUPPORTING THIS TRIAL WHICH IS ONLY RECRUITING PARTICIPANTS AGE 75 AND OLDER WHO DO NOT HAVE AN INDICATION TO RECEIVE A STATIN MEDICATION FOR SECONDARY PREVENTION. IT'S A PRIMEY STUDY OF STATINS IN 20,000 PARTICIPANTS OVER THE AGE OF 75. EVEN MORE IMPORTANT FROM A GERIATRICIANS PERSPECTIVE IS THAT THE PRIMARY OUTCOME FOR PREVENTIBLE IS A GERIATRIC RELEVANT OUTCOME. NAMELY THE PRIMARY COMPOSITE OF DEATH, DEMENTIA OR PERSISTENT DISABILITY. IT IS A PRAGMATIC TRIAL, IT IS DONE THROUGH PC ORNET AND NIA AND IT WILL BE USING AN EMR PHENOTYPE AND THERE'S BEEN COMMUNITY ENGAGEMENT FROM THE VERY OUTSET OF THE APPLICATION GOING IN TO THE LAST YEAR OF THE PLANNING FOR THE RECRUITMENT THAT HAS JUST GOTTEN UNDER WAY AND THERE ARE A GROUP OF 10 PREVENTERS ALL OF WHOM ARE 75 AND OLDER, POTENTIAL PARTICIPANTS WHO HAVE BEEN CRITICALLY IMPORTANT IN ADVISING THE STEERING COMMITTEE AT EVERY POINT ALONG THIS PROCESS. FINALLY IN TERMS OF ACCESS, AND PARTICULARLY IN LIGHT OF COVID, THIS AS A PRAGMATIC TRIAL BY DESIGN HAD JUST A SINGLE IN-PERSON VISIT AT THE TIME OF RANDOMIZATION, THIS MAY BE ABLE TO BE MODIFIED FOR THOSE IN WHOM IT'S REQUIRED TO ALLOW FOR VIRTUAL ENROLLMENT AND ELECTRONIC CONSENTING AND THEN THE FOLLOW UP VISITS ARE ALL BEING DONE WITH A COMBINATION OF IN-HOME ASSESSMENTS AND A TELEPHONE COGNITIVE BATTERY WHICH SHOULD GREATLY FACILITATE RECRUITMENT INTO THIS TRIAL AS WELL AS RETENTION AS IT GETS UNDERWAY. SO THE NEXT SLIDE ARE THE REFERENCES THAT I CITED FOR BOTH OF THESE TRIALS AND I WILL TURN IT NEXT, I BELIEVE TO DR. KOHRT. >> THANK YOU, MARK. ARE YOU ABLE TO HEAR ME? OKAY, FOR THOSE OF US WHO WORK IN THE ARENA OF GERIATRICS AND GERONTOLOGY IT COMES VERY NATURALLY TO US TO INCLUDE OLDER ADULTS IN OUR RESEARCH. SO I THOUGHT TODAY IT MIGHT BE HELPFUL INSTEAD OF LOOKING BACKWARDS HISTORICALLY AT WHAT HAS CONTRIBUTED TO OUR SUCCESS IN DOING SO THAT IT MIGHT BE WORTH WHILE TO TAKE A FORWARD LOOK AT HOW WE AT THE UNIVERSITY OF COLORADO ARE PLANNING TO HELP OUR COLLEAGUES OUTSIDE GERIATRICS AND GERONTOLOGY TO MEET THE NIH POLICY--IN YOUR INSTITUTIONS, CLINICAL AND TRANSLATIONAL SCIENCE AWARD AND PARTICULARLY IF YOU'VE GONE THROUGH A COMPETING RENEWAL IN THE LAST COUPLE OF YEARS, YOU'RE AWARE THERE WAS A NEW SECTION THAT WAS REQUIRED TO BE INCLUDED, CALLED THE ISP SECTION OR INCLUSION OF SPECIAL POPULATIONS. AND SO WHAT I'M GOING TO SHARE WITH YOU TODAY ARE SOME OF THE GUIDELINES THAT WE PUT IN PLACE FOR HOW WE WERE GOING TO ADDRESS THIS IS PARTICULARLY FOR OLDER ADULTS AT COLORADO. BEFORE 2019 WE DID NOT HAVE A WAY OF ASSESSING THE SUCCESS OF THE ENROLLMENT OF OLDER ADULTS IN CLINICAL RESEARCH AT OUR INSTITUTION BECAUSE WE DIDN'T HAVE A QUERIABLE DATABASE THAT PROVIDED THE INFORMATION THAT WE WOULD NEED. IN 2019, WE IMP LELTED A POLICY WHEREBY ALL RESEARCH PROTOCOLS HAD TO UTILIZE A CENTRALLY MANAGED CLINICAL TRIAL MANAGEMENT SYSTEM AND THE 1 WE USE IS ONCORE. AND THIS NOW PROVIDES US WITH THE MEANS OF HAVING INVESTIGATES TRACK IN THE CENTRAL DATABASE A NUMBER OF METRICS ABOUT THE NUMBER OF INDIVIDUALS THEY ARE ENROLLING IN THEIR PROTOCOLS AND ALLOWS US TO QUERY THAT ACROSS THE INSTITUTION. SO WE OUTLINES A 3 STEP PROCESS WHEREBY WE WOULD EVALUATE HOW WE'RE DOING AS AN INSTITUTION IN INCLUDING OLDER ADULTS IN--I WILL START OUT WITH JUST CLINICAL TRIALS RATHER THAN BROADENING IT TO ALL CLINICAL RESEARCH SO THE FIRST STEP IN THIS PROCESS IS TO IDENTIFY CLINICAL TRIALS THAT HAVE THE INTENTION OF ENROLLING ADULTS AGE 65 OR OLDER. SO WE DO THAT BY LOOKING AT THE AGE RANGE, AND ASSESSED BY THE PROTOCOL. AND IF THE ANSWER TO THAT QUESTION IS NO, THEN THE NEXT STEP IS GOING TO BE TO LOOK AT WHETHER THE EXCLUSION OF OLDER ADULT SYSTEM APPROPRIATE AND AS [INDISCERNIBLE] THERE ARE MANY REASONS TO NATURALLY EXCLUDE OLDER ADULTS FROM RESEARCH SO THIS WILL BE A STEP, TAKESSA A BIT MORE LEG WORK TO GO THROUGH THOSE AND TRY TO THEN PARTITION THEM INTO THOSE WHO DID HAVE A GOOD EXCLUSIONARY RATIONAL OR DID NOT. AND THEN OUR THIRD STEP IS THAT IF THEY DID PLAN TO IDENTIFY--TO ENROLL OLDER ADULTS, DID THEY ACTUALLY SUCCESSFULLY ENROLL THEM AFTER THE TRIAL STARTED? NEXT. SO IN 2019 WE GOT A FIRST LOOK AT HOW WE'RE DOING AS AN INSTITUTION. WE HAD ALMOST 700 NEW PROTOCOLS IN 2019 THAT INDICATED AN INTENT TO ENROLL OLDER ADULTS OVER THE AGE OF 65. THAT MEANS THAT ALMOST 2/3RDS OF THE NEW PROTOCOLS THAT WERE REGISTERED AT OUR INSTITUTION IN 2019 HAD CHECKED THAT THEY DID NOT PLAN TO ENROLL ADULTS AGE 65 OR OLDER AND WE HAVE NOT YET GONE THROUGH THE PROCESS OF EVALUATING WHETHER THAT WAS APPROPRIATE OR NOT SO THAT IS IN PROCESS. AND WE JUST STARTED LOOKING AT THE NEXT STEP OF THIS, ABOUT THE SUCCESS OF ENROLLING OLDER ADULTS AND I DON'T ACTUALLY HAVE ANY DATA FOR THE METRIC OF 65 YEARS OF AGE OR OLDER BUT WE DO HAVE ANOTHER THRESHOLD IN THERE OF AGE 50 OR OLDER AND ONLY ABOUT 500 OF THOSE PROT COLS HAD ENROLLED EVEN 1 PARTICIPANT THAT WAS AT AGE 50 OR OLDER. NOW IT'S POSSIBLE THAT MANY OF THESE TRIALS HAVE NOT ACTUALLY STARTED ENROLLING YET, WE SPECIFICALLY HAVE NOT MOVED INTO LOOKING AT 2020 DATA BECAUSE THE IMPACT OF THE COVID PANDEMIC ON RECRUITMENT WHICH ESSENTIALLY STOPPED FOR MANY MONTHS. BUT WE WILL HAVE THIS FOR 2019 TO SEE HOW WE'RE DOING THEN AND THEN WE PLAN TO IMPLEMENT SOME STRATEGIES TO IMPROVE THIS SO WE'LL BE ABLE TO USE THAT AS OUR BENCHMARK, WHERE WE WERE AND LOOK AT HOW WE CAN CHANGE THE NEEDLE GOING FORWARD. NEXT SLIDE, PLEASE. SO WHAT ARE THE STRATEGIES TO PLAN TO HELP INVESTIGATORS MEET ACROSS THE INCLUSION LIFE SPAN POLICY IS TO--IS LOOKING AT OUR DATABASE, IF WE HAVE RESEARCH UNITS EITHER DIVISIONS OR DEPARTMENTS WHO APPEAR TO BE WHO APPEAR TO BE AVOIDING THE INCLUSION OF OLDER ADULTS IN THEIR RESEARCH WHEN WHEN IT WOULD BE APPROPRIATE FOR THEM TO BE INCLUDED, WE PLAN TO REACH OUT TO THEM TO SEE IF THEY'RE AT LEAST INTERESTED IN HEARING FROM US ABOUT HOW THEY MIGHT CONSIDER IMPROVING THIS IN THE FUTURE. AND THEN WE ALSO PLAN TO DEVELOP SOME GENERAL CAMPUS WIDE OR HAVE SOME GENERAL CAMPUS WIDE WORKSHOPS THAT WOULD BE AVAILABLE TO ANYONE WHO'S INTERESTED IN LEARNING HOW TO INCLUDE OLDER ADULTS IN THEIR RESEARCH. AND THE WORKSHOP CONTENT IS GOING TO BE FOCUSED IN 3 GENERAL AREAS THE FIRST 1 WILL BE INFORMATION ON WHY IT'S IMPORTANT TO INCLUDE OLDER ADULTS IN RESEARCH AND WE'VE THAT'S IMPORTANT TODAY. THE SECOND 1 IS WE THINK IT'S IMPORTANT TO HELP INVESTIGATORS DEVELOP ELIGIBILITY CRITERIA BECAUSE I THINK THIS IS OFTEN A DAUNTING TASK FOR INVESTIGATORS WHO AREN'T FAMILIAR WITH WORKING WITH OLDER ADULTS AND THAT JUST USING CHRONOLOGICAL AGE IS OFTEN NOT APPROPRIATE, YOU KNOW 18 YEAR-OLD CAN BE OUT RUNNING MARATHONS AND ANOTHER 80 YEAR-OLD CAN BE HOME BOUND AND BARELY ABLE TO GET OUT OF A CHAIR. SO DEVELOPING ELIGIBILITY CRITERIA, THAT TARGET THE HEALTH, PHYSICAL, MENTAL WHATEVER PARAMETERS OF SPECIFIC RESEARCH QUESTIONS THAT HAVE TO BE ADDRESSED. IDENTIFYING OR DEVELOPING CRITERIA OTHER THAN CHRONOLOGICAL AGE THAT WILL HELP THEM FOCUS THEIR COHORT APPROPRIATELY AND THEN THE FINAL GENERAL AREA WILL BE STRATEGIES FOR HOW TO RECRUIT AND RETAIN OLDER ADULTS IN CLINICAL TRIALS. NEXT PLEASE. AND I WANT TO ACKNOWLEDGE THE WORK OF 1 OF MY COLLEAGUES IN THE DIVISION, KATIE NEHRING WHO IS AN EVALUATION SPECIALIST WHO IS HELPING TO DEVELOP THESE INNOVATIVE PLANS FOR HOW WE WANT TO ENHANCE RECRUITMENT AND RETENTION OF OLDER ADULTS. ONE INTERESTING WAY WE ARE GOING TO TRY IS TO TRY TO TRAIN SOME OLDER ADULTS TO BE RESEARCH SPECIALISTS WHO CAN ACTUALLY BE THE RECRUITERS FOR SOME OF THESE TRIALS. AND THEN THE OTHER APPROACH THAT WE WANT TO TRY IS TO DEVELOP WHAT WE'RE CALLING RESEARCH ROAD SHOWS, WHERE WE CAN GO TO SPECIFIC GEOGRAPHIC AND CULTURALLY DIVERSE COMMUNIIES TO HELP FOSTER THE RECRUITMENT OF OLDER, UNDERREPRESENTED MINORITY RESEARCH PARTICIPANTS. AND WITH THAT I WILL HAND IT OVER TO CONSUELO. >> THANK YOU SO MUCH, IF I'M CORRECT, I THINK WE'RE RUNNING SHORT ON TIME, SO I WILL TRY TO GO QUICKLY TO THE NEXT SLIDE. SO, I WANT WANTED TO SHARE ABOUT SOME OF THE WORK WE'RE DOING IN OUR RECRUITMENT INNOVATION CENTER SO WE HAVE A CENTER FUNDED BY THE NATIONAL CENTER FOR ADVANCEMENT OF TRANSLATIONAL SCIENCE AS WELL AS THE NATIONAL LIBRARY OF MEDICINE. THE FOCUSES ON IMPROVING AND ENHANCING RECRUITMENT AND RETENTION OF CROSS MULTICENTER TRIALS SOIME 1 OF THE PIs OF THAT CENTER ALONG WITH PAUL HARRIS AND THE IMAGE THAT YOU'RE LOOKING AT IS WHAT WE THINK ABOUT AS THE CONTINUUM OF RECRUITMENT, IT IS FOCUSED IN THIS SENSE ON THE INDIVIDUAL, SO THE PATIENT, THE PARTICIPANT, THE FAMILY, AND THINKING ABOUT THIS RECRUITMENT AND THE DIFFERENT RESOURCES AND TOOLS THAT WE MIGHT BE OFFERING AT ANY STAGE ACROSS THE CONTINUUM. THE REASON I WANTED TO HIGHLIGT THIS IS PART OF OUR RECRUITMENT INNOVATION CENTER, WE'VE ACTUALLY DONE CONSULTATIONS ON MORE THAN A 220--SORRY, 220 CLINICAL TRIALS. AND THATIA JUST SINCE WE'VE BEEN FUNDED FOR THE LAST 4 YEARS. AND AMONGST THOSE 220 TRIALS, WE ARE ACTUALLY PROVIDING INSIGHTS, CONSULTATIONS AND RESOURCES FOR STUDIES THAT INCLUDE INDIVIDUALS WHO ARE ONLY IN THE PEDIATRIC ICU, ALL THE WAY TO GROUPS LIKE MARK DESCRIBED WITH THE PREVENTIBLE STUDY, SO SOLELY INDIVIDUAL WHO IS ARE 75 AND OLDER. SO THE RANGE OF EXPERIENCE THAT WE HAVE AND REALLY THINKING THROUGH WHAT THE--EVER THINKING ABOUT THE COMPOSITION OF THE TEAM, WHETHER OR NOT INDIVIDUAL--WHETHER OR NOT THE INCLUSION-EXCLUSION CRITERIA FOR THE POPULATION OR WHETHER NOT INDIVIDUALS WHO MOST MEET IN THE STUDY ARE GOING TO BE UNINTENDEDLY EXCLUDED BY SOME OF THOSE INCLUSION, EXCLUSION CRITERIA. BUT LAWN MOWER REALLY FRAMES THE WORK THAT WE'RE DOING IS A COMPREHENSIVE RECRUITMENT AND RETENTION PLAN SO FOR EACH STUDY THAT WE'RE ACTUALLY INVOLVED IN, THIS RECRUITMENT AND RETENTION PLAN WHERE WE'RE THINKING ABOUT ACROSS THIS CONTINUUM HOW WE INCREASE AWARENESS, OPPORTUNITIES AS WELL AS PROVIDE THE IMPORTANCE--IMPORTANT TOOLS TO ENGAGE INDIVIDUALS IN A WAY THAT THEY ACCEPT AND INTEREST AND BUILD TRUST IN AND ARE WILLING TO PARTICIPATE IN THE STUDY AND WE INCLUDE IN THAT PROCESS OF THE CONTINUUM ACTUALLY RETURN OF RESULTS. NEXT SLIDE. AS PART OF OUR RECRUITMENT AND INNOVATION CENTER, WE DO HAVE A STRONG EMPHASIS ON MINORITY RECRUITMENT AND I KNOW THAT WE CERTAINLY HAVE TALKED ABOUT MINORITY RECRUITMENT THROUGHOUT THE DAY, AND I THINK IT'S VERY IMPORTANT THOUGH THAT WE RECOGNIZE ALL OF THE FOCUS ON JUST THE INDIVIDUALS AND CULTURALLY TAILORING THE MATERIALS AND MAKING SURE THAT THEY HAVE THE INFORMATION AND THE LANGUAGE THAT THEY SPEAK OR WOULD PREFER, ALL THOSE THINGS ARE IMPORTANT BUT WE'VE ALSO FOUND IT'S CRITICAL TO ACTUALLY PROVIDE, INSTRUCTION, TRAINING, COACHING FOR THE RESEARCH TEAMS SO WE'VE CREATED A MASS ONLINE COURSE. IT'S A FREE COURSE ON C OURSERA, FASTER TOGETHER IS THE NAME OF THAT COURSE, IT HAS 8 MODULES AND IT GOES THROUGH THOSE CRITICAL PIECES ACROSS THAT CONTINUUM OF HOW YOU ACTUALLY NOT JUST ACKNOWLEDGE THAT PEOPLE FROM SPECIFIC GROUPS HAVE A GOOD REASON PERHAPS TO DISSTRUOF THE RESEARCH BUT VALIDATING THAT AND TALKING THROUGH ACTUALLY WHAT YOU ARE GOING TO DO TO ENHANCE THAT. AND THEN THE LAST SLIDE I HAVE IS I WAS HOPING TO TALK A LITTLE BIT ABOUT THE--IF YOU COULD GO TO THE LAST SLIDE, I WAS HOPING TO TALK A LITTLE BIT ABOUT SOME OF THE WORK WE'RE DOING IN COVID-19 TRIALS. SO WE HAVE CONSULTE ON ABOUT 25 COVID-19 STUDIES. YOU KNOW THE NUANCES AROUND ACTUALLY ENGAGING INDIVIDUALS IN A STUDY WHEN THERE'S NO PROVEN EFFECTIVE TREATMENT AT LEAST AT THE BEGINNING OF THE PANDEMIC AND THE KINDS OF INFORMATION PEOPLE NEEDED WHEN THERE'S SO MUCH DISINFORMATION THAT'S PRESENT WAS REALLY CRITICAL BUT 1 OF THE THINGS THAT WE SAW THAT MANY STUDIES WEREN'T PREPARED FOR WAS THAT MANY INDIVIDUALS WHO HAD COVID OR DIAGNOSED WITH COVID OR AT INCREASED RISK FOR COVID WERE INDIVIDUALS WITH LIMITED ENGLISH PROFICIENCY AND STUDY TEAMS WERE NOT REALLY PREPARED TO MAKE THEIR MATERIALS AVAILABLE IN MULTIPLE LANGUAGES,% NOT JUST THE RECRUITMENT MATERIALS BUT ALSO THE CONSENT FORM AND COMMUNICATING BACK AND FORTH WITH INDIVIDUALS IN THAT REALM SO WE'VE SEEN THIS INCREASED NEED FOR STUDY TEAMS TO UNDERSTAND THOSE NUANCES AND NOW TO COMMUNICATE MOST EFFECTIVELY WITH INDIVIDUALS THAT THEY WOULD BE INVITING TO PARTICIPATE IN THEIR STUDIES OR ACTUALLY WHO ARE STUDY PARTICIPANTS. SO WHAT YOU'RE SEEING HERE IS JUST A PORTFOLIO OF SOME OF THE MATERIALS WE CREATED AND YOU CAN SEE SOME OF THE DIFFERENT LANGUAGES THAT WERE TRANCEALATED INTO AND STARTING 1 OF THE THINGS WE STARTED TO DO IS NOT JUST TRANSLATE MATERIALS FROM ENGLISH TO OTHER LANGUAGES, BUT START WITH MATERIALS IN THE NATIVE LANGUAGE FIRST. SO I THINK I WILL STOP THERE I'M NOT SURE IF WE HAVE TIME FOR QUESTIONS. SNRKSZ THANK YOU. I ASSUME PEOPLE CAN HEAR ME, I APOLOGIZE FOR THE TECHNICAL DIFFICULTIES THEY SEEM TO ALL BE CONCENTRATED ON OUR PANEL WE RAN OVER A LITTLE BIT. WE HAVE TIME FOR 1 QUESTION, WAS THERE ANYTHING FROM THE AUDIENCE JEROME OR SHOULD WE DO IT INTERNALLY? SO LET ME TAKE A CHAIR'S PREROGATIVE AND ASK THE 1 QUESTION WE'RE ALLOWED, I APPRECIATE ALL THE PANELISTS PROVIDING RESOURCES, I WILL LOOK UP THE COURSERA COURSE, THAT LOOKS GREAT, AND I KNOW MICHELLE HAD SOME OTHERS AS WELL, MARK YOU MENTIONED COGNITIVE AND PHYSICAL FUNCTION OUTCOME MEASURES IS THERE A-- >> DESIGN WILLIAM DALE POINTED OUT SOME OF THESE TOOLS THAT WE ROUTINELY USE AS PART OF GERIATRIC ASSESSMENT SO THE FUNCTIONAL OUTCOME FOR PREVENTIBLE AS AN OUTCOME OF THE REPORT OF THE DISABILITY IN 1 OF THE 6 ACTIVITIES OF DAILY LIVING COMBINED WITH 1 OF THE PROMISE MEASURES FOR THE NIH TOOL KIT, PHYSICAL PERFORMANCE OUTCOME MEASURE AND THEN IN FOLLOW UP, AS WELL, THERE WILL BE THE SHORT PHYSICAL PERFORMANCE BATTERY, THE SPPB, WILL BE COMPLETE INDEED HOME ASSESSMENTS. THE COGNITIVE BATTERY IS BUILT IN MIND AND MODIFY FRIDAY THAT ASSESSMENT AND WILL BE ADMINISTERED LARGELY OR ENTIRELY THROUGH TELEPHONE. SO THOSE INSTRUMENTS ARE AVAILABLE ON THE PREVENTIBLE WEBSITE, PEOPLE CERTAINLY FEEL FREE TO REACH OUT TO ME AND I WOULD BE HAPPY TO SHARE THAT. >> GREAT AND YOU MENTIONED RCCM REFRESH YOUR RECOLLECTION SHOP RELATED? >> YES, SO TO PUT IN A MR. UG AND THIS IS A GOOD SEGUE TO THE NEXT PANEL BECAUSE SEVERAL OF ITS PANELISTS ARE INVOLVED WITH ME ON THE PLANNING GROUP FOR THE NIA SPONSORED RCCN GROUP WHO IS PUTTING TOGETHER A WORKSHOP ON JUST EXACTLY THESE TOOLS THAT ARE NEEDED TO INCORPORATE INTO CLINICAL TRIALS FOR OLDER ADUTS THAT IS PLANNED FOR FEBRUARY 23rd AND 24th, SO YOU SEE ANNOUNCEMENTS COMING OUT ABOUT THAT VERY SOON. >> GREAT. THANK AND YOU ONCE AGAIN THANK YOU TO ALL OF OUR PANELISTS FOR TODAY AND WE WILL PASS THE TORCH TO TOPIC AREA 4 TO WRAP US UP. >> THANK YOU VERY MUCH. THE TOPIC AREA NUMBER 3, I WILL NOW MOVE TO TOPIC AREA NUMBER 4, DATA ANALYSIS AND STUDY INTERPATION, I WILL TURN IT OVER TO DR. HEATHER ALLOR E AND DR. SHAKHNOVIC H. >> CAN YOU HEAR ME? >> YES, SO THANK YOU FOR STICKING WITH THIS I AM VALENTINA SHAKHNOVICH, CHILDREN'S MERCY KANSAS CITY, I FOCUS ON CLINICAL TRIALS IN CHILDREN AND WILL OFFER PERSPECTIVES ON DATA ANALYSIS AND INTERPRETATION, MY PARTNER IN CRIME AND CO-CHAIR DR. HEATHER ALLORE IS A PROFESSOR OF GERIATRIC MEDICINE AND BIOSTATISTICS AT YALE WHERE SHE'S THE DIRECTOR OF BIOSTATISTICS FOR THE YALE PROGRAM ON AGING SO I THINK SHE WILL BE ABLE TO PROVIDE INSIGHTS FROM A GERIATRIC PERSPECTIVE. HEATHER WILL INTRODUCE SOME OF OUR OTHER SPEAKERS JOINING US TODAY. >> THANK YOU VERY MUCH. SO TODAY OUR PANELISTS AND THIS WILL BE IN THE ORDER THAT THEY ARE SHARING THEIR PERSPECTIVES IS ROBERT GOLUB, SHE IS FROM THE NORTHWESTERN UNIVERSITY, FINEBERG SCHOOL OF MEDICINE, HE IS ALSO THE DEPUTY EDITOR OF JAMA AND HIS RESEARCH INTERESTS ARE IN COMPREHENSIVE CARE OF THE ADULT, MEDICAL DECISION MAKING AND PREVENTIVE CARE. THEN WE'LL HEAR FROM KAREN BA NDEEN-ROCHCEREBELLUMS, CHAIR OF BIOSTATICS AT THE JOHNS HOPKINS BLOOMBERG SCHOOL OF PUBLIC HEALTH AND SHE'S ALSO JOINT ME APPOINTED TO THEIR SCHOOL OF MEDICINE AND NURSING. AND SHE IS THE CO-PI OF THE JOHNS HOPKINS OLDER AMERICANS INDEPENDENCE CENTER AND ALSO PART OF THE CENTER FOR LEADING INNOVATION AND COLLABORATION AND INTEGRATION ACROSS LIFESPAN ENTERPRISE COMMITTEE. HER RESEARCH INTERESTS INCLUDE GERONTOLOGY, SHE'S BEEN A BROOK DALE NATIONAL FELLOW AND CO DIRECTS A TRAINING PROGRAM IN BIOSTATISTICS AND EPIDEMIOLOGY OF AGING. THEN, WE WILL HAVE DR. JAY MAGAZINER, FROM THE UNIVERSITY SCHOOL OF MARYLAND MEDICINE. HE IS PROFESSOR OF EPIDEMIOLOGY IS PUBLIC HEALTH. HE'S CHAIR OF THE DEPARTMENT OF EPIDEMIOLOGY AND PUBLIC HEALTH AND ALSO THE DIRECTOR FOR THE CENTER FOR RESEARCH ON AGING WHOSE MISSION IS TO ADVANCE INTERDISCIPLINARY AGING RESEARCH ACROSS THE UNIVERSITY OF MARYLAND. HE ALSO IS THE FOUNDER OF THE UNIVERSITY OF MARYLAND ADDED BALTIMORE'S LONG-TERM CARE PROJECT WHICH IS AN UNL BRELLA ORGANIZATION ESTABLISHED TO RECRUIT AND OVERSEE RESEARCH IN MARYLAND NURSING HOME, BALTIMORE HIP STUDIES AND PROGRAM DESIGNED TO EVALUATE OUTCOMES, DEVELOP AND TEST INTERVENTIONS TO IMPROVE OUTCOMES AFTER HIP FRACTURE, THE PROGRAM ON AGING, TRAUMA AND EMERGENCY CARE WHICH IS DESIGNED TO INCREASE THE--ON THE PEDE YET RICK PERSPECTIVE AND THEN I WILL SHARE THE GERIATRIC PERSPECTIVE BEFORE OPENING IT UP TO THE PANEL. TINA? >> THANKS HEATHER. NEXT SLIDE. SO THE MOST COMMON APPROACH TO DATA ANALYSIS IN PEDIATRIC TRIAL SYSTEM TO GROUP CHILDREN BASED ON THEIR CHRONOLOGIC AGE INTO AGE BINS SO WE THINK OF THENY O NATE, INFANT, CHILD AND ADOLESCENT. THE PROBLEM WITH USING AGE BINS AS THE SOLE BASIS FOR YOUR DATA ANAL S&P THAT IT MISSES THE TRENLENDOUS AMOUNT OF VARIABILITY IN ORGAN MATURATION AND ORGAN PHYSIOLOGY THAT IS CAPTURED WITHIN ANY SINGLE AGE BIN, PERHAPS THE MOST INTUITIVE AGE GROUP WHERE THIS IS EVIDENT ARE THENYONATES AND INFANTS WHERE THE ORGAN PHYSIOLOGY IN A PRETERM ESPECIALLY A VERY EARLY PRETERM INFANT IS VERY DIFFERENT THAN THAT IN A NEAR TERM OR FULL TERM INFANT. THIS CAN HAVE SIGNIFICANT CONSEQUENCES IN PHARMACOLOGY TRIALS FOR EXAMPLE, HERE I'M SHOWING YOU DATA OF WHAT THE PHARMACOLOGIC PROFILE OF A TYLENOL SUPPOSITTORY LOOKS LIKE IN THENYONATAL H-BIN AS A CONSEQUENCE OF INCLUDING PRETERM BIRTH VERSE US INFANT SO ON THE BAR GRAPH, CAN YOU SEE THAT BECAUSE OF THE EXTREME PREMATURITY IN THE PERMIABILITY OF THE NEONATAL GUT SEEN IN PRETERM INFANTS WE'RE ACTUALLY SEEING FAR GREATER CONCENTRATIONS EVER THE DRUG GIVEN COMPARED TO THE FULL TERM INFANTS THAT MIGHT BE BINNED NOT SAME AGE GROUP IN THE IN CONTEXT OF CLINICAL TRIAL. THAT OF COURSE PRESENTS A PROBLEM BECAUSE BY POOLING THOSE DATA WE'RE ACTUALLY IGNORING A VERY IMPORTANT AND VERY OBVIOUS DIFFERENCE IN THE PHARMAICOLOGIC BEHAVIOR IN THE CONSEQUENCES OF THAT DRUG. THIS THEME OF AGE IS NOT SYNONYMOUS OF MATURITY TRANSLATES BEYOND THENYONATAL AND INFANT POPULATION. I'M SHOWING YOU HERE A PICTURE OF 4 GIRLS WHO ARE BORN THE SAME MONTH AND THE SAME YEAR, SO VERY CLOSE AND CHRONOLOGIC AGE AND I THINK YOU CAN APPRECIATE RIGHT OFF THE BAT HOW DIFFERENT THEIR PHYSIOLOGIC MATURITY RATING REALLY IS, YOU'RE LOOKING WITHIN THAT VERY NARROW AGE SPECTRUM AT PREPUBESCENT GIRLS ALONG WITH PERIAND POST BUT BESSENT GIRLS WHERE WE CAN EXPECT THE ORGAN PHYSIOLOGY TO BE VERY DIFFERENT IN THESE 4 INDIVIDUALS THAT WOULD HAVE BEEN BINNED IN THE VERY SAGE AGE BIN. NEXT SLIDE, PLEASE. AGE IS NOT SYNONYMOUS WITH SIZE AND IT CAN BE REALLY CHALLENGING TO TEASE OUT AGE EFFECT FROM SIZE EFFECT IN PEDIATRIC DATA. HOWEVER IT'S VERY IMPORTANT TO DO SO AND TO EXAMINE YOUR DATA IN DIFFERENT WAYS. IN THE PANEL GRAPHS, I'M SHARING WITH YOU DATA FROM OUR GROUP WHERE WE LOOKED AT THE DRUG CLEARANCE OF INFLICKSA MAB, BIOLOGIC MEDICATIONS IN THE TOP PANEL I'M SHOWING YOU DRUG% CLEARANCE AS A FUNCTION OF AGE AND AT FIRST GLANCE WHEN WE TAKE A LACK AT THE RAW CLEARANCE DATA GENERATE INDEED IN INVESTIGATION, WE SEE THAT CLEARANCE APPEARS TO INCREASE WITH AGE, HOWEVER, WHAT YOU'RE ACTUALLY SEEING IN THAT GRAPH IS THE RESULTS OF SIZE, NOT AGE AT ALL. SO WHEN WE NORMALIZE THE DATA FOR THE VARIABILITY AND SIZE OF THE INDIVIDUAL'S INVOLVED IN THIS PEDIATRIC TRIAL, WE CAN APPRECIATE THAT THE CLEARANCE OF THIS PARTICULAR DRUG IS ACTUALLY VERY STABLE ACROSS THE ENTIRE PEDIATRIC AGE RANGE. THIS--THIS PARTICULAR ATTENTION TO SIZE IS ESPECIALLY IMPORTANT IN THE 21st CENTURY WHERE WE ARE CURRENTLY LIVING THROUGH THE PEDIATRIC OBESITY EPIDEMIC. CURRENTLY IN THE UNITED STATES 1 IN 5 CHILDREN ARE AFFECTED BY OBESITY. WE CAN'T AFFORD TO EXCLUDE THESE CHILDREN FROM CLINICAL TRIALS. WE NEED TO BE ABLE TO FIGURE OUT HOW TO BEST ANALYZE AND INTERPRET THE PHARMAICOLOGY DATA GENERATE INDEED THESE INDIVIDUALS. WHETHER THAT'S ADJUSTING THE PHARMAICOLOGY DATABASED ON SIZE OR AGE OR BOTH BECAUSE AS CAN YOU SEE, FROM THIS PICTURE OF FIFTH GRADERS YOU CAN HAVE CHILDREN OF VERY DIFFERENT SIZE BUT OF THE SAME AGE BE INVOLVED IN A CLINICAL TRIAL THAT CAN IMPACT YOUR DATA ANALYSIS SIGNIFICANTLY. NEXT SLIDE PLEASE. IF OUR GOAL IS TO INCLUDE CHILDREN ACROSS THE ENTIRE PEDIATRIC AGE RANGE IN THE SAME CLINICAL TRIAL, IT IS GOING--IT IS NOT SAFE FOR CHILDREN TO SWALLOW SOLID MEDICATIONS SO PILLS UP UNTIL ABOUT 6 OR 7 YEARS OF AGE. OBVIOUSLY THERE ARE EXCEPTIONS TO THIS RULE. WHAT THAT MEANS IS IF YOU WANT TO INCLUDE CHILDREN UNDER 6 OR 7 YEARS OF AGE IN AN INVESTIGATION, YOU ARE GOING TO BE COMPOUNDING EITHER A LIQUID OR A DISINTEGRATING FORMULATION OF THE DRUG AND IT BECOMES EXTREMELY IMPORTANT TO THINK THROUGH WHETHER THE FORMICOLOGY DIFFERENCES YOU MAY SEE AS A CONSEQUENCE OF THIS OR DUE TO YOUNGER AGE OR ACTUALLY FORMULATION EFFECT. DURING TODAY'S PRESENTATIONS I THINK WE'VE HEARD QUITE A BIT ABOUT THE POWER OF PRAGMATIC TRIALS ESPECIALLY GENERATING DATA THAT GENERALIZABLE AND WILL PRESENT THE HETEROGENEITY IN THE REAL WORLD. I THINK WHEN IT COMES TO PRAGMATIC TRIALS IN PEDIATRICS, WE HAVE TO BE VERY THOUGHTFUL ABOUT TEASING OUT AGE EFFECT FROM AGAIN FORMULATION EFFECT BUT ALSO DIET EFFECT AND WE THINK ABOUT THE DIETS OF CHILDREN ACROSS THE FIRST 2 YEARS OF LIFE, WE ESSENTIALEE GO FROM A VERY PREDICTABLE, VERY LIMITED ALL LIQUID DIET, TO THE INTRODUCTION OF SEMISOLIDS AND SOLIDS, ALL OF WHICH HAVE CONQUENCES FOR DRUG, FOOD INTERACTIONS THAT ARE NOT NECESSARILY DUE TO AGE PER SE BUT MAY APPEAR TO INFLUENCE PHARMAICOLOGIC DATA WITHIN A GIVEN AGE BIN. WE ALSO HAVE TO BE THOUGHTFUL ABOUT PROGMATIC AND LONGITUDINAL TRIALS ESPECIALLY WHERE WE REALLY NOT CONTROLLING HOW THE CHILDREN TAKE MEDICATIONS AT HOME. THIS IS INCREDIBLY IMPORTANT BECAUSE I BET MOST OF YOU TAKE MEDICATIONS WITH A TBLASES OF WATER. THIS SIMPLY ISN'T TRUE FOR KIDS. THE MAJORITY OF CHILDREN WILL TAKE THEIR MEDICATIONS WITH JUICE, THIS CAN HAVE PROFOUND CONSEQUENCES ON FORMACOLOGY DATA--PHARMAICOLOGY DATA GENERATED. AS AN EXAMPLE, I'M SHOWING YOU THE INFLUENCE OF APPLE JUICE ON THE TIME CONCENTRATION TIME PROFILE OF AN ALLERGY MEDICATION. THE BLUE DOTS IN THE BLUE LINE REPRESENT WHAT KINDS OF SYSTEMIC CONCENTRATIONS OF A DRUG CAN BE ACHIEVED IF THE MEDICATION IS TAKEN WITH WATER LIKE AN OLDER CHILD OR AN ADULT. ON THE OTHER HAND ALL THE OTHER LINES--PLEASE GO FORWARD, ALL OF THE OTHER LINES ON THAT GRAPH REPRESENT WHAT HAPPENS TO THAT SAME DOSE OF THE MEDICATION BUT WHEN IT'S TAKEN WITH APPLE JUICE AS THE CHILD MIGHT DO AT HOME. TO MAKE THIS KIND OF DRIVE THIS POINT HOME EVEN FURTHER FWE THINK ABOUT APPLE JUICE IN THE PEDIATRIC DIET, IT IS ESSENTIALLY UCIBOLLITIOUS AS AN ADAATIVE IN MANY FOODS, PLUS AS THE DRINK OF CHOICE OR SCHOOL OF CHILDREN, SUCH THAT CHILDREN UNDER 10 CONSUME THE MAJORITY OF APPLE JUICE IN THE NATION. SO WE HAVE TO BE THOUGHTFUL ABOUT THE DISCIPLINARIEST EFFECT AND OUR INTERPRETATION OF AGE VERSUS DISCIPLINARIEST EFFECT WITHIN THE CONTEXT OF SOME OF THESE PRAGMATIC TRIALS AND MAKE AN EFFORT TO CAPTURE THOSE DATA UPFRONT SO THEN WE CAN INVESTIGATOR THE CONSEQUENCES DURING THE DATA ANALYSIS AND INTERPRETATION. NEXT SLIDE, PLEASE. IF WE'RE GOING TO CAPTURE MEANINGFUL DATA IN PEDIATRICS WE HAVE TO USE AGE APPROPRIATE EQUIPMENT AND OF COURSE AGE APPROPRIATE OUTCOME MEASURES. THIS MEANS BEING FAMILIAR AND BEING VERY COGNIZANT OF THE DIFFERENT UPPER AND LOWER LIMITS OF NORMAL FOR VITAL SIGNS AND COMMONLY EMPLOYED LABORATORY STUDIES FOR EXAMPLE. SO HEART RATE OF 60 IN YOU AND I OR AN ADOLESCENT CHILD CAN BE VERY NORMAL, WHILE THAT SAME HEART RATE IN A BABY INDICATES PRETTY SEVERE BRADY CARDIA, SIMILARLY WITH SCREENING LABS OR ANY SORT OF OUTCOME, LAB MEASURES, WE HAVE TO ACCOUNT FOR THE AGE EFFECT ON SOME OF THE MOST COMMON EMPLOYED LABORATORIES AND INVESTIGATIONS SUCH AS LIVER FUNCTION TESTS, HEMOGLOBIN LEVELS, ET CETERA. WHEN WE'RE MEASURING OUTCOMES FOR EXAMPLE, GOING TO THE PREVIOUS TALK IN SOME OF THE CARDIAC TRIALS, FOR EXAMPLE, IF WE'RE USING A BLOOD PRESSURE CUFF IN THE CONTEXT OF A PEDIATRIC TRIAL SPANNING A LARGE AGE RANGE WE HAVE TO MAKE SURE WE HAVE THE APPROPRIATELY SIZED EQUIPMENT TO CAPTURE BLOOD PRESSURE MEASUREMENTS. IF YOU'RE AN INVESTIGATOR LIKE MYSELF, I HAVE IT TO MAKE SURE THAT BY STUDYING CHILDREN WITH OBESITY I NOT ONLY HAVE AGE APPROPRIATE BUT SIZE APPROPRIATE EQUIPMENT READILY AVAILABLE BECAUSE--WOB 40 KILO-RANGE. NEXT SLIDE, PLEASE. BEING ABLE TO GENERATE DATA IN ALL OF THESE DIFFERENT SUBPOPULATIONS WITHIN PEDIATRICS IS AS YOU'VE HEARD THROUGHOUT DIFFERENT PRESENTATIONS IS INCREDIBLY IMPORTANT IN ORDER TO MAKE OUR DATA PLEENINGFUL AND GENERALIZABLE TO THE REAL WORLD SITUATION. HOWEVER, PRACTICALLY IT'S NOT ALWAYS FEASIBLE, FORTUNATELY WE DO HAVE SOME REALLY NEAT NEW PHARMACOLOGY TOOLS TO HELP US START TO UNDERSTAND WHAT GENERALIZABILITY MIGHT LOOK LIKE. SO THIS IS AN EXAMPLE OF A PHYSIOLOGICALLY BASED PHARMAICOLOGIC MODEL, A COMPUTER PLATFORM TOOL WHERE YOU CAN TAKE THE PHYSIO CHEMICAL PROPERTIES OF A DRUG THAT YOU CAN READILY GET, AS INPUT FROM THE THE DRUG LABEL FOR EXAMPLE AND THEN CAN YOU ACTUALLY SIMULATE IN A VIRTUAL PATIENT WHAT THAT DRUG WOULD DO IN THE BODY WITH DIFFERENT PHYSIOLOGIC PARAMETERS. SO PERHAPS INCREASED GUT PERMEABILITY IN THE PRETERM BABE OR INCREASED ORGAN SIZE IN CHILDREN WITH OBESITY AND WHAT CONSEQUENCES THOSE PHYSIOLOGIC CHANGES OR THE TWEAKS YOU MAKE TO THOSE PHYSIOLOGIC CHANGES VIRTUALLY WILL HAVE ON YOUR OUTPUT WHICH IS A DRUG CONCENTRATION PROFILE PREDICTED BY THIS MODELING TOOL. I AM NOT SUGGESTING THAT MEAS MODELING TOOLS SHOULD REPLACE REAL LIVE DATA HOWEVER, WHAT I AM SUGGESTING IS THAT THEY CAN BE INCREDIBLY POWERFUL TOOLS TO HELP US AUGMENT DATA ANALYSIS AND INTERPRETATION AND START GENERALIZE THINK AT LEAST SOME VIRTUAL SIMULATED DAILY BASIS THEA THAT CAN POTENTIA WILY BE THEN GENERALIZABLE TO A PARTICULAR SUBSET OF PATIENTS WHO PERHAPS ARE UNDERREPRESENT INDEED A PARTICULAR INVESTIGATION. IN THE VERY LEAST THEY CAN START SURVING AS A STARTING POINT FOR MAKING EDUCATED TRIAL DESIGNS. THAT HELP US AVOID SOME OF THOSE PK SURPRISES THAT THEY WERE TALKING ABOUT EARLIER. THE BEAUTY OF THESE MODELS TO ME IS THAT THEY'RE NOT LIMITED TO POODIATRIC PATIENTS, AS YOU'LL HEAR HEATHER TALK ABOUT SOME OF THESE THEMES THAT WE'VE IDENTIFY INDEED PEDIATRICS ARE DIRECTLY TRANSLATABLE TO OLDER ADUTS AND THERE'S NOTHING TO SAY THAT WE CAN'T TWEAK THE PHYSIOLOGY COMPARTMENT OF THIS PARTICULAR MODEL, TO ACTUALLY MODEL AND SIMULATE WHAT HAPPENS IN AN OLDER INDIVIDUAL, OF COURSE IF WE KNOW WHAT ALL OF THE PHYSIOLOGIC PARAMETERS ARE. SO WITH THAT I WILL HAND THINGS OFF TO HEATHER TO TOUCH ON SOME ADDITIONAL THOUGHTS ABOUT THE NUANCES OF DATA ANALYSIS AND INTERPRETATION IN THE OLDER ADULT. >> THANK YOU VERY MUCH. NEXT SLIDE, PLEASE. SO I BOTH TINA AND I HAVE A LONGER TALK THAT IS AVAILABLE ON THE WEBSITE THAT THOSE OF YOU WHO'VE REGISTERED HAVE ACCESS TO, SO, WE'RE JUST TAKING ELEMENTS OF OUR TALKS. SO 1 OF THE THINGS I REALLY WANTED TO TOUCH ON IN OUR DATA ANALYSIS AND THE THEME OF OUR OVERALL WORKSHOP IS REALLY TO CONSIDER NOT ONLY THE TRIALS BUT ALSO OBSERVATIONAL STUDIES AND SO 1 APPROACH IS CALLED A LIFE COURSE ANALYSIS AND THINK WE CAN PROBABLY ALL AGREE TODAY BASED ON ALL THE TALKS WE'VE BEEN HEARING THAT THE WORLD HEALTH ORGANIZATION OF HEALTH MAY ACTUALLY REALLY FIT WHAT WE'RE TRYING TO TALK ABOUT. AND THAT IS THAT HEALTH IS A STATE OF COMPLETE PHYSICAL, MENTAL AND SOCIAL WELL BEING AND NOT NEARLY THE ABSENCE OF DISEASE OR INFIRMITY AND THAT DISEASE-HAVE--VIRULENCE THAT DEFINITION HAS BEEN AROUND SINCE 1946. NOW THERE'S QUITE A FEW PEOPLE WHO'VE BUILT A FANTASTIC CAREER AND INSIGHTS IN LIFE COURSE ANALYSIS AND THAT REALLY INTEGRATES BIOLOGY AND SOCIAL PROCESSES. AND IN THAT THERE'S THE EXAMINATION OF HEALTH OVER TIME AND IT INVOLVES CONSIDERING HOW TRAJECTORIES EVOLVE OVER TIME, OVER THE LIFE COURSE AND WHAT IS RELATED TO THAT EVOLUTION OF THAT STRAY JECTORY JECTORY OVER TIME. NEXT SLIDE. SO I'M JUST GOING TO TOUCH UPON DATA HARMONIZATION BECAUSE I THINK 1 OF THE THINGS WE ALL FACE IS, WELL, HOW ARE WE EVER GOING TO HAVE THE DAT SAN FRANCISCO TO BE ABLE TO LOOK OVER A LONG TIME SPAN TO BE ABLE TO CONSIDER HOW DISEASES WILL--WE HEARD FROM THE NATIONAL LIBRARY OF MEDICINE EARLIER TODAY. SO JUST TO MAKE PEOPLE AWARE OF THE NUMBER OF INITIATIVES THERE'S A CITATIONOT BOTTOM OF THIS SLIDE BUT THERE'S A NUMBER OF INITIATIVES ABOUT DATA ELEMENTS, ABOUT STANDARDS, REPORTING FORMATS, THERE'S A COMMENT INITIATIVE, CORE OUTCOME MEASURES AND EFFECTIVENESS TRIALS, SO, AND THERE'S MANY THAT ARE VERY DISEASE SPECIFIC DATA HARMONIZATION PROJECT SO THAT'S 1 WAY TO TURN TO START BEING ABLE TO USE DATA ACROSS AGE SPANS AND ACROSS DIFFERENT INVESTIGATIONS. NEXT SLIDE. SO THEN IF WE HAD THIS BIG DATA WHAT DO WE DO? WELL THERE IS THE BIG DATA TO KNOWLEDGE PROGRAM AND THAT SUPPORTS RESEARCH AND DEVELOPMENT OF INNOVATIVE TOOLS AND TRANSFORMATIVE APPROACHES. SO THAT IS A COMMON AVAILABLE THROUGH THIS COMMON FUND LINK AT THE BOTTOM OF THE PAGE AND THERE YOU WILL FIND THAT THERE ARE MANY DIFFERENT SORT OF BIOMEDICAL DATA SCIENCE RESOURCES, THERE'S INTERACTIVE WAYS TO ANALYZE BIOMEDICAL DATA, THERE'S SOFTWARE, TOOLS, METHODS TO HELP BETTER UNDERSTAND HOW 1 MIGHT WORK WITH LARGE AND SOMETIMES COMPLEX DATA. NEXT SLIDE. SO NOW I'M JUST GOING TO REFLECT MAYBE A LITTLE MORE DEEPLY ON SOME OF THE ANALYTIC CONSIDERATIONS. SO WE HAVE BEEN HEARING ABOUT TRIALS THROUGHOUT THE DAY AND WE'VE HEARD ABOUT SOME OF THESE TREATMENT EFFECTS FROM HIGHLY SELECTIVE TRIALS. AND THAT THEY SHOULD NOT BE EXTENDED TO THE POPULATIONS THAT WERE NOT INCLUDED BUT THEY OFTEN ARE, SO WHAT'S THE PROBLEM? WELL THIS HIGHLIGHTS THAT THERE'S A DIFFERENCE BETWEEN THE ESTIMATE OF THE SAMPLE AVERAGE TREATMENT EFFECT AND THE POPULATION AVERAGE TREATMENT EFFECT. SO WHEN WE GET WORRIED ABOUT SELECTION ISSUES THAT MIGHT NOT BE A PROBLEM WITHIN THE SAMPLE IF QUEER LOOKING AT THAT SAMPLE AVERAGE TREATMENT EFFECT, ASSUMING THERE ARE NO DROP OUTS, AND NO--THERE'S FULL COMPLIANCE, WHICH MIGHT NOT BE REALISTIC BUT IF WE WANT TO GENERALIZE AND OBTAIN THE POPULATION AVERAGE TREATMENT EFFECT, THEN THAT SELECTION OF WHO GOT INTO THE TRIAL REALLY MAY BE A SOURCE OF BIAS, AND THEREFORE THAT'S WHERE THE HESITANCY ABOUT EXTENDING THE RESULTS FROM HIGHLY SELECTIVE TRIALS TYPICALLY OF EFFICACY ARISES. OTHER ELEMENTS THAT WE GET CONCERNED ABOUT IS ATTRITION WHICH CAN RESULT IN INCOMPLETE DATA. SO STUDIES THAT REQUIRE MULTIPLE FOLLOW UP VISITS, ARE OF A LONG DURATION OR HAVE HIGH RISK GROUPS MAY HAVE HIGHER ATTRITION, MAY MAY HAVE MORE NONCOMPLIANCE AND THESE ARE WAYS WE HAVE MISSING DATA. THIS CAN BECOME PROBLEMATIC FOR ANALYSIS OR INTERPRETATION, AND EARLIER TODAY, WE HEARD ABOUT WAYS TO HELP PARTICIPANTS IN YOUR STUDY OR YOUR TRIAL NOT DROP OUT AND BE ABLE TO MEET THOSE STUDY VISITS AND OFTEN OVER LONG PERIODS OF TIME. NEXT SLIDE. ONE OF THE THINGS I WOULD LIKE TO BRING UP BUT WE DON'T HAVE TOOLS FOR IS NEIGHBORHOOD DISADVANTAGE AND THERE'S A TOOL CALLED AREA OF APX OR ADI AND THAT IS COMPRISED OF 17 EDUCATIONAL EMPLOYMENT, HOUSING QUALITY POVERTY MEASURES AND THIS CAN BE DOWN TO A NEIGHBORHOOD LEVEL OF APPROXIMATELY 1500 PERSONS. IT'S BEEN VALIDATED ACROSS THE U.S., IT'S BEEN CREATED REFINED AND VALIDATED AND IT'S DISSEMINATED THROUGH THE NEIGHBORHOOD ATLAS PLATFORM AND ALSO BEEN HIGHLIGHTED THROUGH THE NIAs WEBSITE, WHAT I WOULD LEGAL LIKE TO HAVE US THINK ABOUT AS WE'VE BEEN TALKING ABOUT NOT 1 OF THE PROBLEMS THAT HASN'T BEEN ENOUGH INCLUSION OF PERSONS FROM DISADVANTAGED AREAS IS YET, POSSIBLY INVESTIGATORS DON'T REALIZE THE WEALTH EVEN WITHIN 1 COMMUNITY HOW THAT THERE MAY BE QUITE A BIT OF DIVERSITY WITHIN AN AREA. --HOW COULD YOU USE THIS TOOL IN SAMPLING STRATEGIES SO THAT YOU ARE REFLECTING THE POETIC UPONNULATION THAT HAS THE CONDITION AND YOU ARE INCLUDING PEOPLE ACROSS ALL COMMUNITIES. SOMETHING ELSE TO THINK ABOUT AS WE ANALYZE DATA IS META-ANALYSIS AND SUBGROUPS SO META-ANALYSIS INCLUDE SYSTEMATIC, CRITICAL ASSESSMENTS AT THE LITERATURE, DATA SOURCES THAT FORM THE BODY OF EVIDENCE AND LEAD TO THE ABILITY TO GENERALIZE. THESE ARE OFTEN HOW SOCIETIES ARE MAKING GUIDELINE PART OF THEIR LITERATURE REVIEW TO MAKE GUIDELINE RECOMMENDATIONS, IT MAY BE HOW INDIVIDUAL PRACTITIONERS ARE TRYING TO MAKE GUIDELINE OR FOLLOW GUIDELINES OR MAKE TREATMENT DECISIONS SO IT'S IMPORTANT TO CONSIDER THESE. HOWEVER, REPORTING GUIDELINES FOR JOURNALS DIFFER AND SOMETIMES THIS MAKES META-ANALYSIS FOR AGE GROUPS, OR OTHER FACTORS DIFFICULT. WE HEARD EARLIER FROM THE NATIONAL LIBRARY OF MEDICINE THAT THERE IS JUST AN AGE SCAT GORY OF AGE 65 OR OLDER BUT WE'VE JUST BEEN HEARING FROM TINA ABOUT DIFFERENCES IN PHYSIOLOGY AND MATURITY FROM THE PEDIATRIC PERSPECTIVE, BUT WE ALSO KNOW THIS IS TRUE IN LATER LIFE, THAT THERE'S QUITE A FEW CHANGES. SO IF WE DON'T HAVE MORE GRADATIONS, THEN WE'RE PROBABLY NOT REALLY ABLE TO DO THIS. LET'S TALK ABOUT STRALTIFICATION, IT MAY BE BASED ON THE RISK OF AN OUTCOME BUT IT GENERALLY FROM A BIOSTATTISTICAL VIEW POINT SHOULD BE PREPLANNED, AND THAT SHOULD BE ALIGNED WITH THE DESIGN AND ANALYSIS OF THE STUDY OR TRIAL. RISK STRATAMAY CAPTURE OTHER RELEVANT FACTORS SUCH AS CO-MORBIDITIES OR SOCIOLOGICAL DEMOGRAPHIC FACTORS. SECONDARYY OR SUBGROUP ANALYSIS, INFLATING THE TYPE 1 ERROR DUE TO MULTIPLE COMPARISONS AND SHOULD ADJUST FOR THE SIGNATURES NOVEMBER CANC THRESHOLD. THUS, WHEN THERE IS THE RECOMMENDATION TO PRESENT SOME OF THE AGE GROUPS OR RACE ETHNICITY GROUPS, THROUGH REPORTING OF THE RESEARCH RESULT, THIS MAY SHOW THAT THERE WAS NO DIFFERENCE BUT THAT IN DIFFERENT AGE OR RACE SEGMENTS BUT IT COULD BE LARGELY UNDERPOWERED AND THEREFORE MISLEADING. NEXT SLIDE. SO IN SUBMITTED TORY, MATURITY AND BIOLOGIC SYSTEMS THE HEALTH CAN VERY WIDELY AT THE SAME AGE WHETHER PEDIATRIC OR GERIATRIC POPULATIONS, THE LIFE COURSE ANALYSIS MAY CAPTURE EXPOSURES THROUGHOUT THE LIFE SPAN, AND AND THERE ARE A VARIETY OF HARMONIZATION AND BIG DATA PROJECTS THAT MAY ADDRESS STUDIES OR TRIAL SAMPLING. HEALTH AND RISK FACTORS VARY BY HEALTH AND ETHNIC BACKGROUNDS AS WELL AS SOCIAL DETERMINANTS OF HEALTH INCLUDING DEPRIVATION, STRATIFICATION SHOULD BE BASED ON AN OUTCOME AND SHOULD BE PRA PLANNED ALIGNED WITH A DESIGN OR ANALYSIS AND ALTHOUGH I DIDN'T HAVE MUCH TIME TO TALK ABOUT IT, DR. PEDUSI, DID GO IN GREAT DETAIL PRAGMATIC TRIALS AND FOR SO PRAGMATIC DISSEMINATION AND IMPLEMENTATION, THEY SHOULD INCLUDE THE DEGREE TO WHICH THE RESULTS ARE GENERALIZABLE, TO THE TYPICAL PARTICIPANT AND/OR TYPICAL PROVIDER INSTITUTIONS AND COMMUNITIES AND SETTINGS OF CARE. SO NOW WE WILL OPEN UP IT UP TO OUR PAN AND HE WILL WE WILL START WITH DR. GOLUB'S COMMENTS FIRST. THANK YOU. >> THANK YOU VERY MUCH HEATHER AND I WANT TO THANK THE ORGANIZERS FOR INVITING ME BACK TO THIS FOLLOW UP MEETING, MY ROLE AT JAMA IS DEPUTY EDITOR FOR SCIENTIFIC CONTENT SO I'M RESPONSIBLE FOR THE PEER REVIEW PROCESS AT JAMA AND IN LISTENING TO THE PRESENTATIONS I WAS THINKING ABOUT LAWN MOWER KIND OF COMMENTS I MIGHT MAKE THAT WOULD BE HELPFUL. SO FAR THE PRESENTATIONS HAVE REALLY FOCUSED ON I BELIEVE HAVE FOCUSED ON RESEARCHES AND JOURNAL AND JOURNAL EDITORS ARE IN SOME AN UNUSUAL POSITION, WOOER POISED BETWEEN RESEARCHERS AND THE ULTIMATE--AND COMPETITORS IS SOMEWHAT DIFFERENT THAN THE ISSUES THAT HAVE BEEN RAISED SO FAR, SO I THOUGHT I WOULD MAKE A FEW COMMENTS IN A VERY BROADWAY IN THE THINGS WE THINK ABOUT AS IF THERE'S FOCUS PRIMARILY ON RANDOMIZED TRIALS, THE FIRST THING IS TO THINK ABOUT WHAT THE ROLE IS, OF THE JOURNAL AND THE EDITOR AND I THINK THERE ARE REALLY 4 THINGS THAT WE DO, THE FIRST IS WE MAKE A JUDGMENT OF THE VALIDITY OF THE STUDY AND ALL STUDIES ONLY PROVIDE AN ESTIMATE OF THE AND THE FACT THAT THEY'RE LOOKING AT AND OUR GOAL IS TO TRY TO COME UP WITH A JUDGMENT ON HOW LIKELY THAT IS TO BE AN ESTIMATE OF THE TRUTH. AND THE SECOND IS WHAT WE JUDGE FOR OUR PARTICULAR JOURNAL AND THE THIRD IS ASSUMING WE JUDGE IT TO BE VALID AND APPROPRIATE FOR OUR JOURNAL TO OPTIMIZE THE PRESENTATION TO MAKE IT AS POSSIBLE TO THE COMPLETELY CLEAR, PRECISE AND TRANSPARENT AND ULTIMATELY TO BE ABLE TO PROVIDE GUIDANCE TO READERS TO HELP TO INTERPRET THIS INFORMATION CORRECTLY. SO I THOUGHT I WOULD MENTION A FEW PRACTICAL CHALLENGES THAT WE FACE IN THAT ROLE EXPW ALSO MENTION A FEW THINGS RELATED TO PRESENTATION THAT MIGHT BE HELPFUL FOR YOU TO THINK ABOUT. AS FAR AS PRACTICAL CHALLENGES, THE KEY IS SHE THAT WE'RE AT THE DISTAL END OF THE RESEARCH, WE CAN'T BASE RESEARCH ON POOR EXECUTION OF A STUDY OR JUST BAD LUCK, WE CAN'T DO ANYTHING ABOUT THAT, WE HAVE A STUDY THAT WAS COMPLETED THAT WAS SUBMITTED TO US AND I'VE SEEN MANY STUDIES SUBMITTED THAT HAVE FAILED BECAUSE OF PROBLEMS WITH THE STUDY DESIGN THAT WAS NOT PERHAPS THOUGHT THROUGH AS WELL AS IT COULD BE. THE JOURNAL CAN'T RESCUE THAT TYPE OF A STUDY AND PARTICULARLY WITH RANDOMIZED TRIALS, AND WHILE I'M SPEAKING FOR JAMA, I THINK MOST JOURNALS HAVE THE SAME FLAWS. WE FEEL THAT WE'RE LIMITED TO THE STUDY AS DESCRIBED IN THE PROTOCOL AND STATISTICAL ANALYSIS PLAN THAT THE ARTICLE NEEDS TO BE REPORTED WITH COMPLETE FIDELITY UNLESS THERE ARE FORMAL WAYS THAT THE DESIGN WAS MODIFIED AS THE STUDY WAS EXECUTED. SO WHEN WE FIND LIMITATIONS AS PART OF THE PEER REVIEW PROCESS OR JUDGMENT, THE QUESTION IS WHAT--WHAT IS THE APPROPRIATE TO ASK RESEARCHERS TO ADD OR TO CORRECT OR TO MODIFY OR TO REINTERPRET AND I THINK THERE ARE REAL LIMITATIONS IN WHAT WE CAN ASK FOR THAT. I THINK THERE'S AN INTERESTING PARADOX IN THAT WHEN WE DEAL WITH AN OBSERVATIONAL STUDY, COHORT STUDY, CASE CONTROL STUDY, MOST OF THOSE DON'T HAVE PROTOCOLS, MORE AND MORE DO BUT MOST OF THEM DON'T. AND IN FACT, WE FEEL AT GREATER LIBERTY AS EDITORS TO ASK FOR MAJOR CHANGES TO THE ANALYTIC APPROACH IN AN OBSERVATIONAL STUDY THAN WE WOULD BE WILLING TO STUDY IN A RANDOMIZED TRIAL. IT'S AN INTERESTING ISSUE BUT I THINK THAT KIND OF GOES ALONG WITH THE FACT THAT WE CONSIDER RANDOMIZED CONTROL TRIAL HAPPENS TO BE OVERALL MUCH HIGHER QUALITY OF EVIDENCE ALL ELSE BEING EQUAL IN OBSERVATIONAL DATA. ONE THING I WILL LIKE TO STRESS THAT'S BEEN ALLUDED TO IN THE PRESENTATIONS IS THE ABILITY TO DEAL WITH HETEROGENEITY EFFECTS. AS EDITORS WE ARE STUCK WITH WHAT IS PRESENTED WITH THE MEAN STUDY EFFECT THAT HEATHER TALKED ABOUT IS THE AVERAGE EFFECT IN THE STUDY POPULATION BUT THAT CAN BE REALLY MISLEADING. THERE'S BEEN A LOT OF EVIDENCE FROM MANY STUDIES THAT THE AVERAGE EFFECT OR MEAN EEIVET REALLY ONLY APPLIES TO A VERY SMALL PERCENTAGE OF PARTICIPANTS IN THE STUDY THAT MAY HAVE MORE OF AN EXTREME RISK AND THEY MAY BE DRIVING THE AVERAGE EFFECT AND UNLESS YOU CAN TEASE OUT THAT HETEROGENEITY OF WHAT STUDY OUTCOMES APPLY TO WHICH PATIENTS IN THE STUDY, LOOKING AT THE AVERAGE EFFECT MAY SEND A VERY WRONG MESSAGE ABOUT THE APPLICABILITY OF THE STUDY, AND IN A SENSE THIS IS ACTUALLY THE OPPOSITE OF GENERALIZABILITY, IT'S REALLY A QUESTION OF--BUT ONCE YOU GOT THAT IT'S IMPORTANT TO BE ABLE TO TRY TO TEASE OUT WHICH PATIENTS IN THE STUDY ARE GETTING THE BENEFIT AND WHICH ARE NOT. THIS GOES BEYOND DOING 1 AT A TIME SUBGROUP ANALYSIS BECAUSE THAT ALSO CAN BE VERY MISLEADING AND THAT NEEDS TO BE PLANNED INTO THE STUDY, MAKE SURE YOU HAVE ENOUGH PATIENTS TO DO BOTH THE VARIABLE RISK ANALYSIS AND THE ACTIONS ADEQUATELY. BUT THE BOTTOM LINE OF ALL THESE POINTS IS THAT YOU NEED TO PLAN AHEAD, YOU NEED TO DESIGN ALL THESE ELEMENTS INTO THE STUDY BECAUSE IF YOU DON'T AND YOU'RE LEFT WITH POST HOC ANALYSIS, YOU GET A MUCH WEEKER STUDY --WEAKER STUDY OUTCOME. NOBODY WANTS TO REALLY HAVE CONCLUSIONS OF THEIR STUDY BEING THAT ALL WE FOUND IS SOMETHING THAT'S HYPOTHESIS GENERATING OR MORE RESEARCH NEED TREATMENT OF SUBSTANCE ABUSE BE DONE TO DO THAL IN A BETTER WAY TO GET A MORE DEFINITIVE RESULT. AND DR. SUPIANO GAVE A NICE EXAMPLE OF STUDY THAT DID THINK AHEAD AND PLANNED AHEAD AND THE SPRINT TRIAL WHERE THEY PLANNED SOME STUDIES AND THEY POWERED THE STUDY ORIGINALLY TO BE ABLE TO DO HIGH QUALITY SUBSTUDIES WITH WELL DEFINED SUBGROUPS BOTH FIND END POINTS AND ADEQUATE SAMPLE SIZE. SO 1 THING I WANT TO MENTION THAT SOME OF YOU MAY NOT BE AWARE OF IS THE SPIRIT GUIDELINES. I THINK PROBABLY MOST OF YOU ARE FAMILIAR WITH THE CONSORT GUIDELINES FOR REPORTING A RANDOMIZED TRIAL. IF YOU'RE NOT FAMILIAR WITH THE SPIRIT GUIDELINES THEY'RE AAPPEARANCE OF CONSORT BUT STUDY PROTOCOLS. IF YOU FOLLOW THE SPIRIT GUIDE LINES IN WRITING WROWR PROTOCOL, IT MAKES IT MUCH LESS LIKE LEAK YOU WILL LEAVE OUT A MAJOR PROBLEM WITH THE STUDY VALIDITY. IF YOU'RE NOT FAMILIAR WITH THE SPIRIT GUIDELINES, THAT'S S-P-I-R-I-T, GOOGLE THE WHOLE NETWORK OF PANOPLY OF REPORTING GUIDE LINES FOR THE STUDY DESIGN, YOU WILL FIND THE SPIRIT GUIDELINES AND I WOULD URGE YOU IF YOU YOU'RE NOT FAMILIAR WITH THOSE TO SPEND SOME TIME WITH THEM AND USE THEM WITH YOU PLAN YOUR STUDY PROTOCOLS. THE LAST THING I WANT TO MENTION IS SINCE WE'RE TALKING ABOUT PRESENTATION IS JUST A FEW THINGS THAT WE AS EDITORS FIND COMING UP OVER AND OVER IN THE MANAGEMENT AS PRESENTED THAT AT THE BEST MAKE OUR JOBS DIFFICULT BUT AT THE WORST MAYBE LEAD TO A STUDY BEING REJECTED WHERE THAT COULD HAVE BEEN AVOIDED. THE FIRST IS INCOMPLETE METHODS. I KNOW AUTHORS, AT LEAST THE AUTHORS WHO READ THE INSTRUCTIONS FOR AUTHORS ARE CONCERNED ABOUT WORD COUNT BUT IT'S OBLIGATIONS ABSOLUTELY CRITICAL TO PROVIDE A COMPLETE SET OF STUDY METHODS EVEN IF THAT NEEDS TO BE IN PART DONE IN AN ONLINE SEGMENT. IN OTHER WORD FIST WE DON'T HAVE THOSE WE CAN'T REALLY JUDGE THE VALIDITY OF THE STUDY. WE FIND EPPED POINTS AND ANAL SIGNIFICANCE THAT AREN'T IN THE PROTOCOL OR STATISTICAL ANALYSIS PLAN AND THOSE ARE NOT SOMEHOW ACCOUNTED FOR OR CAN BE VERY PROBLEMATIC. LIKE SIMILAR DISCREPANCIES LIKE THE MANUSCRIPT AND PROTOCOL AND STATISTICAL ANALYSIS PLAN. ESPECIALLY IF THE DEFINITIONS ARE PRIMARY AND SECONDARY END POINTS DON'T LINE UP, MAJOR CHANGES IN THE SAMPLE SIZE STATISTICAL APPROACHES IF THOSE HAVE NOT BEEN--DISCREPANCIES HAVE NOT BEEN EXPLAINED. THIS INTERPRETATION OF THE STATISTICAL FINDINGS FOR EXAMPLE INTERPRETING NO FINDINGS AS IF THEY WERE STATISTICALLY SIGNIFICANT OR NO INTERACTION TESTS AND INTERPRETING SUBGROUP RESULTS AS BEING DIFFERENT. MOST HOC ANALYSIS THAT ARE NOT INTERPRETED ACCORDINGLY. AND, 1 THING THAT'S VERY FRUSTRATING AND PATIENT REPORTED OUTCOMES THAT DOANTD HAVE A MINIMAL ESTABLISHED REPORTING DIFFERENCE AND A POSITIVE RESULT OR EVEN A NO RESULT BECOMES VERY CHALLENGING FOR US AS EDITORS TO FIND OUT IF THE POSITIVE FINDING OR NO FINDING MEANING ANYTHING TO CLINICAL CARE. SO I THINK I WILL LEAVE MY COMMENTS THERE AND BE HAPPY TO TAKE QUESTIONS IF THERE'S TIME LATER. >> THANK YOU VERY MUCH. DR. BANDEEN-ROCHE,. >> THANK YOU VERY MUCH. FIRST OF ALL I WANT TO EXPRESS MY APPRECIATION FOR THIS EVENT, I SUPPORT THE ORGANIZERS AND THE LIKE, IT'S REALLY BEEN TERRIFIC. --ARISING THROUGH PEDIATRIC INCLUSION AND GER GAT RICK INCLUSION WHICH OTHER SPEAKERS ALSO HAVE NOTED, WE HEARD TINA TALK ABOUT AGE NOT BEING SOMEWHAT SYNONYMOUS WITH MATURE AITIONZ IN KIDS, AGE IS ALSO NOT SYNONYMOUS WITH BIOLOGICAL AGING OR THE EXTENT OF DECLINE IN OLDER ADULTS, THIS MAKES MEASUREMENT OF FUNCTION VERY IMPORTANT. SOME PEEKERS SPOKE TO THAT, ALSO PHYSIOLOGICAL MEASURES, WHETHER IT BE OF MATURATION OR OF DECLINE AND BIOLOGICAL AGING AND OLDER ADULTS AND IN OLDER ADULTS THERE ARE SUMMARY MEASURES THAT CAN BE HELPFUL TO TRY TO GET AT THESE THINGS. WE'VE HEARD ABOUT FUNCTION BUT ALSO MEASURES OF PHYSIOLOGICAL FITNESS SUCH AS FRAILTY, OR 1 OF THE NOVEL 1S ARISING THESE DAYS IS RESILIENCE. AGE ALSO IS NOT SYNONYMOUS WITH HUMAN SUBJECTS VULNERABILITY. CERTAINLY WE MUST ATTEND TO VULNERABILITY AT THE EXTREME ENDS OF THE AGE SPAN, BUT THERE MAY BE A DANGER OF UNINTENDED AGEISM BY IRBs WHO DULY ATTEND TO VULNERABILITY WITHOUT ATTENDING A STRONGLY TO THE ETHICS OF INCLUDING A FULL RANGE OF INDIVIDUALS SO I CONCUR WITH OTHER SPEAKER WHO IS HIGHLIGHTED THE IMPORTANCE OF MORE RIGOROUSLY DEFINING THINGS LIKE UNACCEPTABLE RISK AND NOT DEFINING THAT THE SIMPLY ACCORDING TO AGE. WE HEARD ABOUT THE HAZARDS OF TOKENISM BY INCLUDING ONLY A FEW INDIVIDUALS IN EITHER OLDER ADULTS OR PEDIATRIC GROUPS WHICH CAN LEAD TO SELECTION, ALSO THAT EXTRAPOLATING TREATMENT EFFECTS VERY OFTEN WILL LEAD TO MISLEADING FINDINGS, NOT ONLY IN KIDS ABOUT YOU ALSO OLDER ADULT AND SO BOTTOM LINE IS I HOPE WE WILL GET OUT OF OUR SILOS IN PEDIATRICS AND GERIATRICS AND DO MORE SYNERGY OF THE SORT THAT'S HAPPENING HERE IN THIS GROUP. IT'S ALSO A CHANCE FOR ME TO HIGHLIGHT THE LIFESPAN GROUP OF THE CTSAs WHICH BRINGS TOGETHER PEDIATRIC AND GERIATRIC RESEARCHERS TO CONSIDER INCLUSION AND OTHER CRITICAL THINGS ACROSS THE LIFE SPAN. SECOND THING I WANT TO DO IS JUST TO HIGHLIGHT A FEW ANALYTIC CONSIDERATIONS, HOPEFULLY COMPLIMENTARY TO THOSE THAT OTHERS RAISED. STATISTICAL APPROACHES WHILE NOT CAPABLE OF FIXING DEFICITS AND DESIGN OR INCLUSION MAY BE ABLE TO HELP ALONG THE ARE WAY AND SO THE FIRST IS SELECTIVITY OF INDIVIDUALS WHETHER IT BE GERIATRIC OR POODIATRIC. FOR EXAMPLE, THE HEALTHIEST INDIVIDUALS OR ONLY IN A LIMITED PART OF THE WHOLE AGE SPAN. AS MUCH AS WE TRY TO AVOID THESE THINGS OR WE MAY TRY TO,A VOID THESE THINGS, SOME SELECTIVITY IS INEVITABLE, IT IS HARD TORE INCLUDE INDIVIDUALS WHO ARE LESS HEALTHY AND SO SOME TECHNIQUES WHICH COULD BE BROUGHT TO BEAR WITH SOME OF THESE ISSUES INCLUDE THE CAUSAL INFERENCE TECHNIQUES, INVERSE PROBABILITY WAITING AND SUCH SEEKING TO BALANCE, IMBALANCES THAT ARISE IN POPULATIONS, TRANSPORTABILITY IS A TECHNIQUE THAT IS BEING STUDIED BY MANY SEEKING TO BALANCE THE BENEFITS OF RANDOMIZATION OF CLINICAL TRIALS TOGETHER WITH GENERALIZABILITY AND OBSERVATIONAL STUDIES, WE OURSELVES HAVE USED WHAT I CALL A FOOT IN THE DOOR QUESTIONNAIRE, OCCASIONALLY SEEKING TO CAPTURE KEY OUTCOMES FROM INDIVIDUALS, PARTICULARLY IN OBSERVATIONAL STUDIES WHO ARE LESS WILLING TO PARTICIPATE SO THAT IMBALANCES PERHAPS COULD AT LEAST BE ADDRESSED THROUGH SENSITIVITY ANALYSIS. HEATHER SPOKE TO THE IMPORTANCE OF HARMONIZATION, IT'S WONDERFUL HOW SHE HIGHLIGHTED MATERIAL ON STANDARDS AND HARMONIZED MEASURE RESOURCES THEN EXIST, BUT THE ISSUE OF HARMONIZATION IS REALLY QUITE BROAD. YOU KNOW MEASURES MAY FUNDAMENTALLY DIFFER ACROSS STUDIES THAT USE SLIGHTLY DIFFERENT VERSIONS OF A GIVEN TRIEWMENT, CERTAINLY ACROSS THE LIFE COURSE, THE SAME INSTRUMENT MAY ASSESS ITS TARGET DIFFERENTLY IN SUBGROUPS BY AGE OR BY RACE ETHNICITY DUE TO CULTURAL ISSUES AND SO STATISTICAL METHODS TO HARMONIZE DO EXIST, THESE AIM TO IMPROVE THE COMPARABILITY OF ASSESSMENT OF THE UNDERLYING TARGET THROUGH ANALYTIC ADJUSTMENTS. MENT AND THEN IN ORDER TO APPLY THESE EFFECTIVELY ANCHORS ARE NEEDED AND THAT'S A MATTER FOR DESIGN. HETEROGENEOUS --HETEROGENEITY--AN D SO CERTAINLY AMONG THE TECHNIQUES THAT MAY DREANGZ THIS ARE BASE LINE CO VARIANT ADJUSTMENTS IF DONE CAREFULLY, EFFECTIVE MODIFICATION OR ADAPTIVE DESIGNS TO RIGOROUSLY INVESTIGATOR SUBGROUPS AS DR. GOLUB WAS JUST RAISING, ANALYSIS THAT ARE CAPABLE OF EVALUATING MOW CALLED MIXTURES OF EFFECTS THAT SUBGROUPS MAY EVIDENCE DIFFERENT EEVENGHTS AND AT LEAST IN SENSITIVITY ANALYSIS MAY BE POSSIBLE TO IDENTIFY IMPERICALLY. AND SO THE THEN THE LAST THING I WANT TO HIGHLIGHT IS THAT WE OFTEN FOCUS ON THE CHALLENGES OF INCLUSION, THAT INCLUSION MAY MAKE OUR STUDIES MORE COMPLICATED BUT PERHAPS IT'S NOT ALL BAD. FOR EXAMPLE, WITH OLDER ADULTS, WE MAY SEE HEIGHTENED EVENT RATES, LEADING POTENTIALLY TO OPPORTUNITIES FOR GREATER POWER, PARTICIPANTS MAY BE VERY HIGHLY DEDICATED AND FINALLY, WE'RE ABLE TO--THE ISSUES WE CONSIDER REGARDING INCLUSION AT THE END OF THE AGE SPAN REALLY DO GENERALIZE TO IMPROVE STUDIES OR OTHER GROUPS THAT ALSO EXPERIENCE HETEROGENERATED AITY AND SELECTIVITY AND SOME OF THESE OTHER THINGS. IT'S REALLY BEEN MY PLEASURE TO PARTICIPATE AND I'M END MY COMMENTS THERE. >> THANK YOU VERY MUCH. DR. MAGAZINER? >> THANK YOU. THANK YOU VERY MUCH, HEATHER, I APPRECIATE IT AND THANK YOU EVERYONE AND FOR THE INVITATION TO BE HERE TODAY. IT HAS BEEN A VERY STIMULATING DAY. I THINK I'M THE LAST PERSON TO COMMENT BEFORE WE HAVE CONCLUDING REMARKS AND IT HAS BEEN A LONG DAY, SO I WILL BE RELATIVELY BRIEF AND WANT TO BASICALLY COME DOWN ON 1 OR 2 IMPORTANT POINTS THAT MAY OR MAY NOT HAVE BEEN MENTIONED AS EXPLICITLY BUT WERE CERTAINLY COVERED THROUGHOUT THE DAY IN MANY OF THE PRESENTATIONS AND I THINK YOU KNOW WE ALL AGREE THAT LIFE SPAN INCLUSION AS WELL AS ALL INCLUSION IN RESEARCH IS VERY IMPORTANT AND CRITICAL AND I THINK DR. COLLINS EMPHASIZED THAT FOR NIH-WIDE AND WE'VE SEEN IT IN MANY PLACES UNFORTUNATELY, WELL,LET'S JUST SAY MOST OF THOSE PARTICIPATING TODAY, IF NOT ALL OF US BUT MOST OF US ARE AMONG THE CONVERTED AND WE THINK THAT'S IMPORTANT TO TRY TO FIGURE OUT WHAT TO IMPROVE ON THAT. WHAT'S UNFORTUNATE IS THAT MANY SCIENTISTS, NOT THOSE THAT THIS CONFERENCE OF COURSE BUT POLICIES AND CLINICIANS WHO USE OUR RESULTS FROM THE STUDIES DO NOT APPRECIATE THE VALUE OR MORE IMPORTANTLY DO NOT UNDERSTAND THE IMPORTANCE OF INCLUSIVENESS AND I THINK WE HAVE A ROLE IN TRYING TO EDUCATE AND INFORM OTHERS OF THE IMPORTANCE OF THIS IN ADDITION TO DOING IT WELL, WE ALSO NEED TO BE SURE OTHERS UNDERSTAND THE IMPORTANCE OF IT. --I THINK OVER THE PAST 30 YEARS OR MORE, THE NIH HAS MADE A LOT OF PROGRESS WITH REGARD TO THE PROCESS OF INCLUSION AND I WANT TO EMPHASIS THE PROCESS, THERE ARE FUNDING REQUESTS THAT REQUIRE INCLUSION, AND THEY TALK ABOUT IT AND EMPHASIZE IT, AND THE REVIEW PANELS CONSIDER IT MONITORING AFTER FUNDING AND PROGECS ARE DONE AND WHILE THEY'RE BEING DONE MONITOR IT AND THEN WE HEARD A LOT ABOUT REPORTING OF INFORMATION AND HOW IT WOULD BE IDEAL TO HAVE SOME CATEGORIES AND BETTER CATEGORIES FOR AGE AND WE DO REPORT ON RACE AND ETHNICITY AND GENDER AND I THINK WE REALLY NEED TO--THE NIH HAS DONE A LOT TO TO CHANGE THE CULTURE OF INCLUSION AND I THINK THAT'S EXTREMELY IMPORTANT AND OVER TIME IT WILL BLEED OVER INTO MANY SECTORS AS A RESULT BUT WE ALSO CAN DO MORE ABOUT WHAT THE DIRECTIONS WE SHOULD TAKE IN THE FUTURE ARE MPLET AND I THINK WHERE I WOULD LIKE TO GO FOR THE NEXT FEW SECONDS IS JUST TALK ABOUT SOME OF THE THINGS THAT MIGHT PLAY INTO WITH DEVELOPING SOME STANDARDS FOR INTERPRETING RESULTS AND REPORTING THE LIMITATIONS OF RESEARCH AND I THINK--I THINK DR. GOLUB STARTED TO TALK ABOUT THIS IN HAVING PROTOCOLS AND HAVING DEVELOPMENTAL STRATEGIES FOR HOW PROT COLS--GENERALIZABILITY OR INDIVIDUAL APPLICABILITY VERSUS WHAT MIGHT BE THOUGHT OF AS SORT OF THE GROUP AVERAGE OF APPLICABILITY. YOU KNOW RESULTS YOU KNOW, I THINK--I THINK, WE NEED TO ASK THE QUESTION WHO DO THE FINDINGS APPLY TO AND WHO WILL BENEFIT FROM THE TREATMENTS THAT ARE BEING TESTED AND THEN HOW ARE THEY ACTUALLY GOING TO BE USED AND WHO WILL THEY BE USED WITH? YOU KNOW THE VARIABILITY AND I THINK WE'VE HEARD ABOUT THAT ALL DAY, THERE'S A TREMENDOUS AMOUNT OF VARIABILITY THAT'S BUNDLED INTO AGE AND IN MANY RESPECTS, AGE IS REALLY--HAS TO BE THOUGHT OF AS MORE THAN JUST THE NUMBER OF SECONDS OR MINUTES OR YEARS SINCE BIRTH. IT'S MORE THAN A CHRONOLOGICAL FACTOR, WE'VE HEARD THAT MANY TIMES. SX HEAT IN MANY, IF BY INCLUDING OLDER PEOPLE IN STUDIES WHILE IT'S IMPORTANT, IT'S NOT ENOUGH. WE NEED TO BE THINKING AT THE SAME TIME OF THE WAY DIFFERENT GROUPS OF OLDER PEOPLE OR DIFFERENT INDIVIDUAL OLDER PEOPLE MIGHT RESPOND TO DIFFERENT TREATMENTS OR HOW THE OUTCOMES MIGHT BE MEASURED IN A WAY THAT CAN BE VIEWED AS MEANINGFUL EITHER IN INDIVIDUALS OR ACROSS INDIVIDUALS IT WOULD BE A BREECH WITH THE WAY THINGS HAVE BEEN DONE TRADITIONALLY IF WE COULD FIGURE THAT OUT. AMONG THE MANY THINGS BUNDLED INTO AGE ARE OF COURSE CO MORBIDITIES AND WE'VE TALKED ABOUT THAT, EARLY LIFE EXPOSE EXPERIENCES, COHORT MEMBERSHIP, WHAT AFFECTS A 70 YEAR-OLD TODAY AND WHAT COMES OUT OF A STUDY OF PEOPLE IN THEIR 70S TODAY MAY NOT BE APPLICABLE 15 OR 20 YEARS FROM NOW, TO THAT SAME 70 YEAR-OLD PERSON AND WE NEED TO CONSIDER THAT IN INTERPRETING RESULTS FROM THE PAST AND LOOKING FORWARD TO WHERE ARE WE WANT OUR WORK TO BE USEFUL IN THE FUTURE. MY POINT AGAIN IS VARIABILITY, THERE'S A LOT OF VARIABILITY BUNKEDEMMED INTO AGE AND I THINK OUR CHALLENGE AND RESPONSIBILITY IS TO IDENTIFY WAYS OF REPORTING ON THE--ON THE STUDY LIMITATIONS SO THAT WE HAVE SOME STANDARDS OR HOW WE REPORT AND HOW WE HELP POLICY MAKERS CLINICIANS AND OTHER SCIENTISTS USE THE RESULTS OF OUR STUDIES IN THE MOST MEANINGFUL WAY BECAUSE I HAVE TO SAY, WE HAVEN'T DONE ENOUGH TO EDUCATE AND HELP THOSE WHO USE THE FINDINGS OF OUR WORK TO REALLY APPRECIATE THE OPTIMAL WAY OF USING IT. I THINK I WILL STOP THERE. >> YAY THANK YOU SO MUCH FOR OFFERING YOUR THOUGHTS AND PERSPECTIVE AND THANK YOU TO ALL OF OUR PANELISTS FOR COMMENTING ON SOME OF THE COMMON THEMES THAT HAVE EMERGED BETWEEN THE PEDIATRIC VARIABILITY AND THE GERIATRIC VALID AND RELIABLABILITY THAT HAVE BEEN CONSISTENTLY IDENTIFIED IN TODAY'S PRESENTATION. ONE THING THAT REALLY STRUCK ME FROM YOUR PRESENTATION JAY IS THIS CONCEPT OF, THERE'S SO MUCH VARIABILITY BUNDLED INTO AGE. AND I'M CURIOUS TO HEAR FROM OUR PANELISTS, 1 THING I COMMONLY HEAR ESPECIALLY FROM CLINICIANS AND OFTEN TIMES THE PATIENTS, ACTUALLY IS CAN THIS VARIABILITY BE CAPTURED BY TAPPING INTO THE ELECTRONIC MEDICAL RECORD FOR RESEARCH PURPOSES? IME CURIOUS TO HEARENTIOUS SPECIALLY FROM A BIOSTATISTICS STANDPOINT WHAT DO YOU GUYS SEE AS SOME OF THE ADVANTAGES AND LIMITATIONS THAT DATA MINING THE EIN, R MAY POSE? WHAT ARE THE OPPORTUNITIES? WHAT ARE THE BARRIERS? JAY WOULD YOU LIKE TO START SINCE YOU WERE OUR LAST SPEAKER? >> NO, ACTUALLY I WOULD LIKE--[LAUGHTER] --BECAUSE I'VE BEEN WONDERING THAT FOR--I'VE BEEN VERY INTERESTED IN THAT AND IF YOU CAN GET AT SOME CONSTELLATIONS OF PEOPLE FROM ALL OF THE WHOLE VARIED INFORMATION THAT MIGHT BE AVAILABLE WITH SOME MOT CUM OF ACCURACY IN THE STANDARD, I'M ONLY 18 EPIDEMIOLOGIST. I WOULDN'T PURPORT TO BE A BIOSTATISTICIAN. >> KAREN, I THINK THE BUCK HAS BEEN PASSED. >> AND THENIME GOING TO PASS IT TO HEATHER. BUT--OKAY, YOU KNOW SO? I WOULD SAY THAT AMONG THE PROS OF COURSE ARE--AS LARGE SAMPLE SIZES WHICH ARE CAPABLE OF IDENTIFYING SUBGROUPS. THERE ARE REAL HAZARDS THOUGH, YOU KNOW INCLUDING THEM MEASUREMENT, WE ALL KNOW THAT PHENOTYPING AND THE EHR CAN BE VERY CHALLENGING DATA THAT ARE NOT COLLECTED FOR RESEARCH PURPOSES MAY INCORPORATE BIASES AND SO I THINK IT'S A VERY INTRIGUING IDEA BUT THE ENTERPRISE PROBABLY WOULD BENEFIT FROM HAVING A GREAT INTERDISCIPLINARY TEAM WHO BOTH CAN BRING THE CONCEPTUAL CLARITY, NOT BIOSTATISTICIANS, OTHER SUBJECT AREA EXPERTS IN AGING AND MEDICINE BUT TOGETHER WITH DATA SCIENTISTS STATISTICIAN SYSTEM EPIDEMIOLOGISTS SO JAY, YOU REALLY SHOULDN'T HAVE PASSED THE BUCK. [LAUGHTER] >> WELL I'LL JUST FINISH UP THAT THERE ARE GROUPS SUCH AS HEALTHCARE SYSTEMS RESEARCH NETWORK, THAT ARE A GROUP OF DIFFERENT HEALTHCARE SYSTEMS THAT COME TOGETHER AROUND THEMES JUST AS YOU SUGGESTED KAREN SUCH AS CANCER OR MENTAL HEALTH DISEASES, JAY IS JERRY GURWITZ, SO THERE ARE AND ALICE ADAMS AND THERE ARE PEOPLE THAT COME TOGETHER WORKING WITH HEALTHCARE SYSTEMS THAT DO VERY HIGH STANDARD DATA COORDINATION AND CLEANING TO HAVE VIRTUAL DATA WAREHOUSES AND WAREHOUSES AND SO I THINK IT'S WHEN THESE HEALTHCARE SYSTEMS HAVE A COMMONALITY AROUND A THEME AND HAVE STANDARDS TO WHICH DATA THAT WOULD GO INTO THOSE DATA WAREHOUSES AND THEN THERE'S A RIGOROUS WAY IN WHICH PEOPLE APPLY TO BE ABLE TO USE THAT RESEARCH, THAT DATA AT A RESEARCH LEVEL BUT IN A VERY SECURE WAY THAT THAT IS ANOTHER DIRECTION THAT WE WILL BE--THAT HAS BEEN VERY SUCCESSFUL FOR SOME VERY LARGE PRAGMATIC TRIALS AS WELL AS OTHER TRIALS. SO, I THINK WE'RE AT THE END OF OUR TIME. I'M JUST SO ENTHUSIASTIC ABOUT EVERYONE'S COMMENTS AND THE DAY SO FAR. I THINK IT'S BEEN ACROSS ALL THE PANELS, IT'S BEEN REALLY GREAT AND I WILL TURN IT OVER TO THE ORGANIZERS FOR OUR CLOSING SESSION. >> THANK YU VERY MUCH TO PANEL 4. WE WILL NOW HAVE HIGHLIGHTS AND SUMMARY OF THE IALL WORKSHOP BY SAMIR SAUMA, BRASH RADZISZEWSKA AND JIM GRIFFIN. >> THANK YOU I'M JIM GRIFFIN EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT AT NIH AND I WANT TO THANK EVERYONE ON BEHALF OF THE CO-CHAIRS AND PLANNING COMMITTEE TO THE SUCCESS OF THIS WORKSHOP INCLUDING ALL THE AMAZING SPEAKERS AND PANEL MEMBERS AND NIH STAFF INCLUDING LEADERSHIP AND EVERYONE WHO'S VIEWING THIS VIRTUAL WORKSHOP, EITHER LIVE OR THROUGH THE ARCHIVE VIDEO WEBCAST. I WOULD REALLY BE REMISS IF I DIDN'T DO A SPECIAL THANKS FIRST TO DR. MARIE BERNARD WHO'S BEEN A STEADFAST SUPPORTER OF THE WORKSHOPS SINCE THE CONCEPTION OF THE FIRST 1 AND HAS BEEN ACTIVELY INGAUGED ALL ALONG. IT'S REALLY JUST BEEN INVALUABLE TO THEIR SUCCESS EMPLOY SECOND OF ALL, AGAIN I WANT TO SINGLE OUT FOR PRAISE JEROME LOCKET WHO KEPT US ALL ON TRACK AND DONE IT WITH GRACE AND HUMOR. FINALLY I WANT TO ALSO RECOGNIZE MY INSTUE DIRECTOR DR. DIANNA BIANCI, NICHD WHO'S DONE A TREMENDOUS AMOUNT OF WORK PROMOTING RESEARCH ON WOMEN'S HEALTH ACROSS THE LIFESPAN INCLUDING PREGNANT AND LACTATING WOMEN AND AS WELL AS INCLUSION OF AS INDIVIDUALS WITH DISABILITIES IN STUDIES FUNDED BY NIH. I WILL TURN IT OVER TO A COUPLE THINGS MERE FROM THE PEDIATRIC PERSPECTIVE VENLT OVER ALL COMMENT I WOULD SAY IS THE FACT THAT KIND OF QUOTING PAUL, WE WALK BY FAITH NOT BY SIGHT AND IN THIS CASE I'M NOT TALKING ABOUT SPIRITUAL FAITH BUT FAITH IN THE SCIENTIFIC METHOD AND EVEN THOUGH INCLUSION DOES POSE CHALLENGES, WE CAN USE THOSE METHODS TO ADVANCE OUR UNDERSTANDING IN HOW TO ADDRESS THESE ISSUES AS WELL AS HOW TO BEST ACCOMMODATE THEM. I ALSO WANT TO JUST AS MANY PEOPLE HAVE UNDERSCORE THE FAITH AND TRUST OF THOSE THAT VOLUNTEER TO PARTICIPATE IN THE RESEARCH STUDIES. I THINK OOGHTS ALWAYS IMPORTANT TO KEEP THAT IN MIND. AS HAS BEEN SAID, I THINK FIRST BY DR. BIANCI, BUT BY MANY OTHERS, CLEARLY CHILDREN ARE NOT LITTLE ADULTS WHICH IS WHY WE HAVE AS 1 EMPHASIS OF INCLUSION POLICY THE INCLUSION OF CHILDREN IN STUDIES FUNDED BY NIH. WE JUST CAN'T GENERALIZE FROM ADULT POPULATION STUDIES TO CHILDREN. LIKEWISE, WE NEED TO PAY SPECIAL ATTENTION TO POPULATIONS THAT ARE SOMETIMS WITH THE BEST OF INTENTIONS EXCLUDED FROM OUR RESEARCH, INCLUDING PREGNANT AND LECITATING WOMEN AND FOR THOSE WHO ARE INTERESTED IN THAT SPECIFIC TOPIC PLEASE LOOK AT THE MATERIAL AND REPORTS FROM THE PRAGMATIC TRIAL LIFE LAC TASK FORCE. DIVERSITY AGAIN IT IS NOT WELL REPRESENT INDEED OUR STUDIES INCLUDING UNDERREPRESENTED MINORITIES ELECTRIC MINORITIES, GENDER MINORITIES, INDIVIDUALS WITH DISABILITIES THESE ARE CHALLENGES AND THEY'RE EXCITING OPPORTUNITIES BUT IT IS SOMETHING AS YOU'VE HEARD THROUGHOUT THE DAY, ALL THE PROGRESS THAT'S BEING MADE TO ACHIEVE THAT GOAL. AS THE CASE WITH THE FIRST WORKSHOP AND WE HEARD THIS THEME A COUPLE OF TIMES, I'M STRUCTURALLY WITH THE SIMILARITY OF ISSUES REGARDING INCLUSION OF INDIVIDUALS ON BOTH ENDS OF THE LIFE SPAN SO WE HAVE TO BE CAREFUL NOT TO SILO WHAT WE LEARN ABOUT INNOVATIVE METHODS TO INCREASE INCLUSION, BY AGE GROUP. WE REALLY HAVE TO BE ABLE TO LOOK AT THOSE AND SHARE THOSE ACROSS THE LIFE SPAN RESEARCH. IF MY CONCLUDING REMARKS AT THE FIRST WORKSHOP, THIS WAS THE BEGINNING OF THE JOWRN TOW ADDRESS INCLUSION ISSUES NOT THE END POINT AND SO WITH THE SECOND WORKSHOP, IT'S IMPORTANT TO NOTE WE'RE AT ANOTHER CRITICAL MILESTONE AS WE ADDRESS THE IMPLEMENTATION OF THE NEW NIH INCLUSION POLICY, BUT IT'S A CONTINUATION OF THAT JOURNEY, IT'S NOT THE CONCLUSION. AND SO WITH THAT I WILL NOW TURN THE VIRTUAL PODIUM OVER TO BARBARA AND WILL PROVIDE CONCLUDING COMMENTS FROM THE GERIATRIC RESEARCH PERSPECTIVE, BARBARA? >> HI, SO MY NAME IS BARBARA RADZISZEWSKA, DIRECTOR AT THE NATIONAL INSTITUTE ON AGING AND FIRST I WOULD LIKE TO EXPRESS GRATITUDE TO PANEL MEMBERS FOR THEIR CONTRIBUTION AND TO THE OGBONNIA OKORONKWO SHOP AND ALSO TO THE AUDIENCE FOR THEIR COMMENTS AND QUESTIONS. NEXT SLIDE, SO I'M JUST GOING TO HIGHLIGHT, VERY BRIEFLY SOME OF THE KEY POINTS THAT WERE RAISED IN THE WORKSHOP. SEVERAL OF OUR SPEAKERS HAVE EMPHASIZED LIMITATIONS AND DANGERS OF OTHER GENERALIZATION AND EXTRAPOLATION OF FINDINGS FROM HIGHLY SELECTIVE CLINICAL TRIALS TO POPULATIONS THAT ARE NOT INCLUDED. SO THIS MEANS WE HAVE TO BE MINDFUL OF THE FACT THAT THE AVERAGE TREATMENT EFFECT IS NOT FLSESLY THE SAME AS THE AVERAGE POPULATION TREATMENT EFFECT AND WE MUST KEEP IN MIND THAT THERE HAVE BEEN SURPRISING FINDINGS ON DOSING AND SAFETY IN PEDIATRIC RESEARCH THAT WE HEARD ABOUT TODAY AND BE AWARE OF THE FACT THAT THERE'S A POTENTIAL THAT'S--THERE MAY BE SIMILAR FINDINGS IN GERIATRIC STUDIES OR STUDIES OF SOME SPECIAL POPULATIONS THAT HAVE THAT TRADITIONALLY NOT BEEN INCLUDE INDEED TRADITIONAL RESEARCH. ONE OF THE KEY POINTS RAISED WAS THE CRITICAL NEED TO CAREFULLY PLAN AND INTENTIONALLY INCLUSIVE POPULATION. THE PLAN IS TO INCLUDE COMMUNITY STAKEHOLDERS, MEMBERS OF THE AFFECTED POPULATIONS AND ACTIVE ENGAGEMENT OF HEALTHCARE PROVIDERS. WE HAVE HEARD OF SEVERAL EXAMPLES OF STUDIES THAT HAVE USED THIS APPROACH, SUCH AS THE DIABETES TELEPHONE STUDY, SPRINT TRIAL AND THE PREVENTIBLE TRIAL THAT JUST STARTED. ANOTHER KEY POINT THAT WE HAVE EMPHASIZED IS THAT CHRONOLOGICAL AGE IS NOT EQUIVALENT TO HEALTH OR FUNCTIONAL STATUS IN OLDER ADUTS JUF JUST AS AGE IS NOT EQUIVALENT TO ORGAN MATURATION OR STAGE OR BODY SIZE IN CHILDREN, THERE IS A VERY LARGE DEGREE OF VARIABILITY IN HEALTH, PHYSICAL OR COGNITIVE STATUS AMONG OLDER ADULTS OF THE SAME AGE AND 1 OF THE CHALLENGES THAT WE HAVE AKENTIFIED IS HOW TO CAPTURE THIS VARIABILITY. SO THIS IS SOMETHING THAT WE WILL CONTINUE WORKING ON. ANOTHER KEY TOPIC, IN OUR WORKSHOP WAS--TIPS TO ACCOMMODATE AND TOOLS. THE 5 Ms OF MIND, MOBILITY, MEDICATION, MOTIVATION AND MATTERS TO ME, HIGHLIGHTS THE IMPORTANCE EVER TRAINING IN AGING RESEARCH TO NONGERIATRICIAN SPECIALIST WHO CONDUCT RESEARCH THAT INCLUDING OTHER ADULTS AND I THOUGHT THAT THE PROGRAM DESCRIBED BY DR. [INDISCERNIBLE] AT THE UNIVERSITY OF COLORADO IS A WONDERFUL EXAMPLE OF THAT AND IN FACT I'M HOPING THAT IT IS AVAILABLE TO THE RESEARCH COMMUNITY IN GENERAL. IT'S VERY INNOVATIVE AND WONDERFUL. ONE OF THE KEY TOPICS DISCUSSED WAS LARGE SIMPLE PRAGMATIC TRIALS AND THEIR POTENTIAL FOR MAXIMIZING DIVERSITY AND INCLUSIVITY IN STUDY SAMPLES, PRAGMATIC TRIALS ARE EMBED INDEED CLINICAL PRACTICE SETTINGS HAVE FEW EXCLUSION CRITERIA AND USE SIMPLE STUDY PROTOCOLS. THE CROSS PARTICIPANT AND PRAGMATIC TRIALS AND LOWER THAN IN TRADITIONAL CLINICAL TRIALS WHICH ENABLES INCLUSION OF LARGE NUMBERS EVER DIVERSE PARTICIPANTS AND PERFORMING PREPLANNED VALID SUBGROUP ANALYSIS. FINALLY, THERE IS A KEY POINT THAT WAS RAISED WAS THE NEED FOR TOOLS AND RESOURCES THAT ARE NEEDED TO SUPPORT THE INCLUSION OF THE TRADITIONALLY AND UNDERREPRESENTED POPULATIONS IN CLINICAL RESEARCH I WILL HIGHLIGHT A COUPLE OF EXAMPLES, 1 OF THE RESOURCES AND SERVICES OFFERED BY THE RECRUITMENT INNOVATION CENTER AT VANDERBILT UNIVERSITY, THAT DR. WILKINS DESCRIBED AND ANOTHER EXAMPLE WAS THE GERIATRIC ASSESSMENT TOOL THAT WE TALKED ABOUT THAT'S BEEN USED IN GERIATRIC CANCER RESEARCH BUT IT'S ALSO APPLICABLE TO OTHER AREAS OF RESEARCH INVOLVING OLDER INDIVIDUALS THAT TOOL IS POTENTIA WILY VERY USEFUL IN STUDYING RECRUITMENT RETENTION AND ADHERENCE. THANK YOU. , HELLO MY NAME IS SAMIR, SAUMA, EYE DIRECTOR OF PLANNING AND EVALUATION AT THE NATIONAL INSTITUTE ON AGING I WOULD LIKE TO THANK MY CO CHAIRS BARBARA AND JAMES FOR AN EXCELLENT JOB PREPARING FOR THIS WORKSHOP. I ALSO WOULD LIKE TO INTRODUCE DON COLBERT WHO WILL BRIEFLY TALK ABOUT THE RELEVANT DISTUGZ WHAT'SY HEARD TO ON THE CURRENT NIH POLICYINGS. GO AHEAD. >> THANK YOU SAMIR. BACK IN DECEMBER OF 2017 NIH ANNOUNCED WHAT SOUNDED LIKE SOMETHING VERY SIMPLE, THAT WE EXPECTED THAT INCLUSION IN THE CLINICAL RESEARCH WE FUND BE AGE APPROPRIATE AND THAT ANY EXCLUSIONS BE JUSTIFIED AND WE ALSO ASK THAT YOU PROVIDE US DAT ON THE AGE OF ENROLLMENT IN YOUR PARTICIPANTS AND I THINK WHAT WE LEARNED TODAY IS THIS IS A LOT MORE COMPLICATED THAN IT MAY SEEM AT FIRST GLANCE, IT'S 1 THING TO SAY THAT YOU'LL INCLUDE DIVERSE AGE GROUPS AND IT'S QUITE ANOTHER THING TO ACTUALLY DO IT AND I WANT TO THANK ALL OF THOSE WHO PARTICIPATED TODAY IN HELPING US UNPACK THESE CONSIDERATIONS FOR STUDY TEAMS AS THEY WORK TO IMPLEMENT INCLUSION ACROSS THE LIFE SPAN POLICY. WE TALKED ABOUT A NUMBER OF CONSIDERATIONS, THINKING ABOUT THINGS LIKE HOW WE OBTAIN INFORMED CONSENT, HOW SOCIAL DETERMINANTS IMPACT THE ABILITY OF OUR PARTICIPANTS TO PARTICIPATE IN OUR STUDIES, WHAT KIND OF BURDEN IS INVOLVED IN OUR STUDY FOR PARTICIPANTS, THINKING ABOUT STRATEGIES TO INVOLVE FAMILY AND COMMUNITIES, THINK BEING THE APPROPRIATE STUDY DESIGNS LIKE ADAPTIVE AND PRAGMATIC TRIALS, HOW WILL WE COMMUNICATE WITH THE PARTICIPANTS? WHAT IS THE--WHAT ARE THE LIMITATIONS OF THE CHRONOLOGICAL AGE CATEGORIES? AND HOW ARE WE GOING TO EVALUATE OUR RECRUITMENT? ONE THING THAT'S APPARENT AND MANY SUCCESSFUL EXAMPLES WE HEARD TODAY IS THAT IT TAKINGS THE ENTIRE SCIENTIFIC COMMUNITY TO REALLY THINK ABOUT AND ADDRESS THESE ISSUES IN ORDER TO SUCCESSFULLY INCLUDE INDIVIDUALS ACROSS THE LIFE SPAN. WE FEED FULL ACADEMIA, ORGANIZATIONS, PHYSICIANS AND ENTITIES BUT AS JIM MENTIONED WE NEED PARTICIPANTS THEMSELVES IN THE DESIGN AND IMP LEMMATION. SO I WANT TO THANK YOU FOR HELPING THINK THROUGH THESE ISSUES SO THAT NIH CAN HELP TO MAKE THUR THAT THE KNOWLEDGE WE GAIN FROM THE RESEARCH WE FUND ISA APLIBLGABLE TO ALL OF THOSE INDIVIDUALS WITH THE CONDITION. THANK YOU. >> --AND SUMMARY WILL BE POSTED IN 2 WEEKS ON THE IALL II WEBSITE AND WHITE PAPERS WILL BE DEVELOPED BY CO-CHAIRS AND PANELISTS FROM THE 4 AREAS THAT WERE DISCUSSED TODAY. BEFORE I GIVE BELIEVE IT OR NOT THE FINAL WORD TO WRAP THIS WORKSHOP, I WOULD LIKE TO THANK A VERY IMPORTANT PERSON WITHOUT WHOM THIS WORKSHOP HAVE NOT RUN SMOOTHLY AND THAT'S DR. JEROME LOCKET WHRO WORKS WITH ME AND I WOULD SAY HE WAS RESPONSIBLE FOR THIS SUCCESS OF THE FIRST WORKSHOP THAT WAS RUN IN 2017 AND HAS DONE IT AGAIN WITH THE WORKSHOP THAT HE HAS WORKED REALLY HARD MONTH AFTER MONTH OF DEDICATION AND EFFORT. THANK YOU JEROME. STANDING OVATION WOULD HAVE BEEN APPROPRIATE NOW IF YOU WERE IN PUNISH AT THE MEETING BUT A HEART FELT THANK YOU WILL HAVE TO DO FOR NOW. THANK YOU DR. BERNARD, FINAL WORDS? >> SO I JOIN YOU SAMIR IN OFFERING A STANDING OVATION FOR DR. LOCKET, I KNOW HE'S BEEN EATING, DRINKING BREATHING THIS WORKSHOP FOR THE LAST MANY MONTHS AND CAN FINALLY EXHALE. I WOULD ALSO LIKE TO THANK AND YOU YOUR CO-CHAIRS, DR. GRIFFIN, DR. RADZISZEWSKA, AND ALL OF YOU WORKED AS AN EXECUTIVE COMMITTEE TO PUSH THIS AGENDA FORWARD AND BRING THIS MEETING TO FRUITION. YOU SEE LISTED HERE, IT'S BEEN LISTED FOR A WHILE NOW ALL THE PEOPLE WHO ARE ON THE TRANSNIH PLANNING COMMITTEE FOR THIS, VERY ROBUST REPRESENTATION OF ACROSS NIH TO HELP US THINK ABOUT WHO SHOULD HAVE BEEN THE PEOPLE TO BE INVITED ON THE PANELS AND WHAT SHOULD BE DISCUSSED FOR THE MEETING AND THEN OF COURSE OUR WONDERFUL PANELISTS, IT WAS JUST AS WE HAD ANTICIPATED GREAT PRESENTATION, GREAT INTERACTIONS AND WE REALLY LOOK FORWARD TO THOSE PEER REVIEW PAPERS THAT WILL COME FROM THIS WORKSHOP, SO IT'S VERY APPROPRIATE AND JEROME GETS THE LAST WORDS SO DR. ROCKET, NEXT SLIDE, PLEASE. >> ALL RIGHT, THANK YOU VERY MUCH, THANK YOU EVERYONE FOR JOINING AND PARTICIPATING IN THE INCLUSION ACROSS THE LIFE SPAN WORKSHOP. IF YOU HAVE ANY QUESTIONS OR COMMENTS, PLEASE FEEL FREE TO E-MAIL NIAPLANNING@NIH.GOV.