DELIGHTED TO OPEN THE 45th NIH ADVISORY COMMITTEE FOR RESEARCH ON WOMEN'S HEALTH. WELCOME. THIS IS A MEETING OPEN TO THE PUBLIC, BROADCAST LIVE ON THE NIH VIDEOCAST NETWORK, BEING RECORDED. JUST A COUPLE HOUSEKEEPING THINGS, RESTROOMS ARE LOCATED BY THE ELEVATOR, THERE'S A STATION FOR COFFEE ON THIS FLOOR AS WELL AS COFFEE SHOP ON THE FIRST FLOOR IN THE A WING, AND ALSO AS A REMINDER, ALL COUNCIL MEMBERS HAVE THE OPTION OF PARTICIPATING REMOTELY FOR ONE MEETING A YEAR, PROVIDED WE HAVE ADVANCE NOTICE. SO WHAT I'D LIKE TO DO FIRST IS DO INTRODUCTIONS AROUND THE TABLE VERY BRIEFLY, PLEASE STATE YOUR NAME AND YOUR UNIVERSITY AFFILIATION. >> LIZ SPENCER, ORWH. >> KIMBERLY GREGORY, CEDARS-SINAI. >> CONNIE WEAVER, PURDUE. >> JUDDY REAGAN, UNIVERSITY OF COLORADO SOOL OF SCHOOL OF MEDICINE. >> SCOTT HULTGREN, WASHINGTON UNIVERSITY ST. LOUIS. >> STACY GELLER UNIVERSITY OF ILLINOIS CHICAGO. >> DAVID PAGE, WHITEHEAD INSTITUTE AND M.I.T. >> DEVRIES, GEORGIA STATE. >> MARY PALMER UNC - CHAPEL HILL. >> CEDARS-SINAI. >> JILL BECKER UNIVERSITY OF MICHIGAN. >> CARMEN GREEN, I'M WITH HER. >> RACHEL JONES NORTHEASTERN UNIVERSITY BOSTON. >> SUSAN WOOD, GEORGE WASHINGTON UNIVERSITY, MILLIKEN INSTITUTE SCHOOL OF PUBLIC HEALTH. >> WENDY (INDISCERNIBLE) UNIVERSITY OF NORTH CAROLINA CHAPEL HILL. >> ANA. >> ROGER, UNIVERSITY OF FLORIDA. >> CAROLYN MISSOURI, YALE UNIVERSITY. >> GREAT. I DO BELIEVE WE HAVE ONE OF OUR NEW ADVISORY COMMITTEE MEMBERS JOINING US BY PHONE. DR. STEFANIK, ARE YOU THERE? MAYBE NOT JUST YET. SHE'S ON THE WEST COAST. SO DR. MARSHA STEFANIK WILL BE JOINING US REMOTELY. THANK YOU ALL FOR BEING HERE. I ALSO WANT TO REMIND YOU, I WANT TO WELCOME OUR GUESTS AS WELL, NIH STAFF, TEAM ORWH AND OTHER GUESTS. DELIGHTED TO HAVE YOU. I NEED TO REMIND COMMITTEE MEMBERS WHILE YOU'RE HERE WORKING FOR THE ACRWH YOU ARE SPECIAL GOVERNMENT EMPLOYEES SUBJECT TO THE SPECIAL GOVERNMENT EMPLOYEES RULES WHICH YOU RECEIVED AS THE STANDARDS OF ETHICAL CONDUCT FOR EMPLOYEES OF THE EXECUTIVE BRANCH DURING YOUR ORIENTATION WHEN YOU WERE APPOINTED. AT EVERY MEETING WE LIKE TO REVIEW THOSE STEPS THAT WE TAKE, IN ORDER TO COMPLY ARE REGULATIONS AND ADDRESS CONFLICTS BETWEEN YOUR PUBLIC RESPONSIBILITIES AND PRIVATE INTEREST. BEFORE EVERY MEETING YOU PROVIDE A GREAT DEAL OF INFORMATION ABOUT YOUR PROFESSIONAL, PERSONAL AND FINANCIAL INTEREST, WE USE THIS AS FOUNDATION FOR ASSESSING WHETHER OR NOT YOU HAVE POTENTIAL OR APPARENT CONFLICTS OF INTEREST THAT COULD COMPROMISE YOUR ABILITY TO GIVE ADVICE. IF THE NEED FOR SERVICE OUTWEIGHS CONFLICT OF INTEREST WE WOULD ISSUE A WAIVER OR RECUSE YOU FROM A PARTICULAR PORTION OF THE MEETING. WE USUALLY WAIVE CONFLICTS OF INTEREST FOR GENERAL MATTERS, BECAUSE WE BELIEVE YOUR ABILITY TO BE OBJECTIVE WILL NOT BE AFFECTED BY YOUR FINANCIAL INTERESTS, BUT WE ALSO RELY A GREAT DEAL ON YOU. SO YOU NEED TO BE ATTENTIVE DURING THE MEETING TO THE POSSIBILITY ANY ISSUE COULD ARISE THAT COULD AFFECT OR APPEAR TO AFFECT YOUR FINANCIAL INTEREST WITH A SPECIFIC PARTY MATTER. IF THIS HAPPENS YOU'LL BE ASKED TO RECUSE YOURSELF FROM THAT PORTION OF THE MEETING. BEFORE WE GO ON, YOU WERE PROVIDED THE MINUTES FROM THE SEPTEMBER 13, 2017, MEETING THAT WERE POSTED ON THE ORWH WEBSITE. A LINK WAS SENT TO YOU FOR YOUR REFERENCE. IS THERE A MOTION ON THE TABLE TO ACCEPT THE MINUTES AS PREPARED? DR. GREEN, SECONDED BY DR. BARRYMER, AUTISM IN FAVOR INDICATE BY SAYING AYE. >> AYE. >> ANY OPPOSED? ANY ABSTENTIONS? OKAY. GREAT. WELL, I DO WANT TO BEGIN BY THANKING THE AMAZING MEMBERS OF OUR ADVISORY COMMITTEE THAT ARE RETIRING FROM SERVICE, THEIR SERVICE TO THE ADVISORY COMMITTEE BUT NOT NECESSARILY SERVICE TO ORWH, YOU'RE NOW PART OF THE ORWH FAMILY, DR. GREEN, BECKER, PALMER, WEAVER. I WANT TO WELCOME SOME NEWEST ADVISORY COMMITTEE MEMBERS, DR. BREWSTER, DR. GREGORY, DR. JONES, DR. STEFANIK WHO MAY HAVE JOINED US. NOT YET. AND DR. WOOD. WELCOME ABOARD. WE'RE DELIGHTED TO HAVE YOU AND WE'RE LOOKING FORWARD TO YOUR INPUT. SO AT THIS POINT I'M GOING TO MOVE TO THE PODIUM AND GIVE OUR DIRECTOR'S REPORT. AND I HAVE UNTIL 9:45. MISS WHITE IS GOING TO KEEP ME ON TIME. I'M TAKING ALLERGY MEDS BECAUSE THIS IS THE ALLERGY SEASON, SO I'M A LITTLE DEHYDRATED HERE. ALL RIGHT. FIRST I WANT TO BEGIN BY -- I ALWAYS LIKE TO SHARE WITH YOU THE AMAZING WOMEN LEADERS WE HAVE AT NIH, AND WE DO HAVE A NEW ACTING NIH INSTITUTE AND CENTER DIRECTOR, DR. JILL HEMESKIRK, YOU MAY HAVE HEARD DR. RODERIC PETTIGREW RETIRED FROM NIH AND DR. HEMESKIRK IS ACTING DIRECTY. IT'S MY PLEASURE TO ALREADY MEET WITH HER IN OUR CAPACITY OF STRATEGIC PLANNING DEVELOPMENT. I LIKE TO BEGIN EVERY TALK BY HONORING THE LEGACY OF THOSE THAT CAME BEFORE, CLEARLY ALL OF US ARE STANDING ON THE SHOULDERS OF THOSE THAT CAME BEFORE, AND DR. RUTH KIRSTEIN WAS THE FIRST WOMEN IC DIRECTOR AND ACTING NIH DIRECT FOR SEVERAL YEARS, THE LATE DR. BERNADINE HEALEY, FULLY APPOINTED. SENATOR MIKULSKI FROM MARYLAND RETIRED, NOW ACADEMIC APPOINTMENT AT JOHNS HOPKINS, OF COURSE DR. VIVIAN PINN, FIRST FULL TIME DIRECTOR OF ORWH, OUR TIME HAS CHANGED, I'M GETTING TO BE IN THE SEAT FOR NOW BUT I ALSO WANT TO RECOGNIZE AND HONOR THE MEMORY OF REPRESENTATIVE LOUISE SLAUGHTER, AMAZING LEADER, IN THE LEGISLATIVE BRANCH, BROUGHT FORWARD INCREDIBLE EFFORTS INCLUDING VIOLENCE AGAINST WOMEN ACT, SHE WAS ONE OF THE CO-AUTHORS OF THAT. AND A VARIETY OF OTHER EFFORTS, SHE'S ONE OF THE FIRST PEOPLE TO HAVE PUT FORWARD SPECIFIC FUNDING FOR EXAMPLE FOR BREAST CANCER RESEARCH. AND ACHIEVED A VERY HIGH RANK IN HER THE ECONOMY POSITIONS. SO WE WANT TO HONOR HER MEMORY AS WELL. I ACTUALLY DO NEED TO CHANGE THIS VIEW TO PRESENTATION VIEW, IF SOMEBODY CAN HELP ME, THAT WOULD BE GREAT. AS WE'RE DOING THAT, CONTROL-P, DOES THAT CHANGE TO PRESENTATION VIEW? DOES ANYBODY KNOW? I CAN DO IT HERE IF YOU JUST TELL ME. AS WE'RE DOING THAT I WANT TO HONOR TEAM ORWH, WHO HAVE DONE ALL THE HARD WORK LITERALLY THEY HAVE DONE ALL THE HARD WORK, AND THEY ARE ALL HERE TODAY. SO I WANT -- OKAY, WE'LL DEAL WITH IT. THAT'S OKAY. THEY ARE HERE AND THEY ARE ALL IN RED BECAUSE WE TAKE THIS PICTURE DURING FEBRUARY, DURING WOMEN'S HEART HEALTH MONTH, AND SO I JUST WANT TO RECOGNIZE THEM. THEY ARE ALL AROUND THE ROOM, AND I LIKE TO DO THIS AT THE BEGINNING OF THIS TALK BECAUSE I WANT YOU TO KNOW THAT THEY ARE THE ONES DOING THIS WORK. SO PLEASE JOIN ME IN THANKING THEM, AT THE BEGINNING OF THE DAY, FOR ALL OF THEIR HARD WORK. [APPLAUSE] THANK YOU, MISS WHITE. APPRECIATE THAT. OKAY. AND I ALSO WANT TO WELCOME OUR NEWEST TEAM MEMBER, DR. NORSEY, PLEASE WELCOME DR. NORSEY, SHE'S THE NEWEST ASSOCIATE DIRECTOR, JOINS US FROM THE NATIONAL INSTITUTE ON DRUG ABUSE, WORKED IN WOMEN'S HEALTH AND ADDICTION FOREMANY YEARS, AN ACCOMPLISHED SCIENTIST, TRAINED IN CLINICAL APPLIED PSYCHOLOGY IN THE VIOLENCE AGAINST WOMEN SPACE AS WELL AS CHILDREN'S WELFARE, SO WE'RE DELIGHTED TO HAVE HER ON BOARD AND I'M SURE YOU'LL HEAR FROM HER IN THE FUTURE. HERE IS MY OUTLINE FOR THE TALK TODAY, IN COLLABORATION AND PARTNERSHIP WE'LL GIVE YOU A SHORT UPDATE ON RESEARCH PROGRAMS AND SABV, TALK ABOUT HOW IMPORTANTS TO TO ADJUST YOUR COURSE WHEN THE FORCES OF WIND ARE CHANGING AROUND YOU, AND UPDATE ON WOMEN IN BIOMEDICAL CAREERS AND QUICK UPDATE ON OTHER ACTIVITIES. FIRST IN TERMS OF OUR COLLABORATIONS WITH OUR INSTITUTE AND CENTER PARTNERS, I DO WANT TO BEGIN WITH SOMETHING THAT IS ON ALL OUR MINDS AS AN INCREDIBLE PUBLIC HEALTH CRISIS, AND I BRING TO YOUR ATTENTION THAT FY 18 OMNIBUS BILL PROVIDED AT LEAST $500 MILLION FOR NIH-FUNDED RESEARCH ON OPIOID ADDICTION, AND THE NIH DIRECTOR ANNOUNCED LAUNCHING OF THE HEEL INITIATIVE, HELPING IVE, HELPING END ADDICTION LONG TERM, TO ADDRESS ISSUES GOING FORWARD. AS YOU KNOW, WE ALL AROUND THIS ROOM KNOW, THE OPIOID CRISIS IS INDEED A WOMEN'S HEALTH ISSUE. JUST TO MAKE THAT CLEAR IN TERMS OF SOME STATS THAT WE NEED TO KEEP IN MIND, IF YOU LOOK AT DIFFERENCES BETWEEN WOMEN AND MEN FROM 2005 TO 2015 OVER 10-YEAR PERIOD, OPIOID-RELATED INPATIENT HOSPITAL STAYS INCREASED 55% IN MEN, 75% IN WOMEN. IN 2014, THE MOST RECENT YEAR FOR DATA ON THIS BEING AVAILABLE, WOMEN HAD HIGHER RATES OF OPIOID-RELATED INPATIENT HOSPITAL STAYS, IN THOSE STATES THAT ARE PURPLE. THAT'S A LOT OF STATES. IN THE STATES THAT ARE BLUE, MEN HAD A HIGHER RATE OF INPATIENT HOSPITAL STAYS, WHITE STATES NO DATA. THAT'S A SURPRISING PICTURE BECAUSE THAT'S NOT HOW THINGS HAVE LOOKED IN THE PAST, REPRESENTING A CHANGE IN PATTERN WE'RE SEEING, INDEED BETWEEN 1999 AND 2015 ACTUAL DEATHS FROM PRESCRIPTION NOW OPIOID OVERDOSES INCREASED 471% IN WOMEN, AND 218% IN MEN. CLEARLY, ALL OF THESE NUMBERS ARE UNACCEPTABLE, AND WE HAVE MUCH WORK TO DO IN THE SPACE. I ALSO WANT TO DRAW YOUR ATTENTION TO THE FACT THAT THERE ARE DIFFERENT PATTERNS BY RACE, ETHNICITY, WE'RE SEEING IF YOU LOOK ON THE TOP RIGHT NON-HISPANIC BLACK MEN ARE HERE, NON-HISPANIC BLACK WOMEN ARE HERE. THIS IS COCAINE. THIS IS OPIOIDS. YOU CAN SEE OVER TIME, THIS IS OVER TIME, INCREASE IN OPIOID USE ESPECIALLY HERE IN NON-HISPANIC BLACK WOMEN. IF YOU COMPARE, THERE'S A CLEAR DIFFERENCE. IN WHITE YOU SEE A TOTALLY DIFFERENT PATTERN. FROM THE BEGINNING, THERE WAS A HIGH RATE OF OPIOID USE AS COMPARED TO COCAINE, SO A DIFFERENT PATTERN. WHAT I DO WANT TO DRAW YOUR ATTENTION TO IS THE FACT THESE RATES ARE EXCEEDING NUMBERS WE'VE EVER SEEN BEFORE, THE PATTERN IS THE SAME FOR NON-HISPANIC BLACK WOMEN, BUT MAGNITUDE IS LOWER FOR BLACK WOMEN, MUCH HIGHER IN THE WHITE POPULATION. AND SO WE NEED TO UNDERSTAND WHAT'S GOING ON IN THIS ADDICTION SPACE, AND THE NATIONAL INSTITUTE FOR MINORITY HEALTH AND HEALTH DISPARITIES RECENTLY POSTED A NEW FUNDING OPPORTUNITY ANNOUNCEMENT ENTITLED "ADDRESSING CHALLENGES OF THE OPIOID EPIDEMIC IN MINORITY HEALTH AND HEALTH DISPARITIES RESEARCH IN THE UNITED STATES." ORWH SIGNED ON TO THE ANNOUNCEMENT TO LOOK TOWARDS ISSUES WE'RE CONCERNED ABOUT. HERE ARE SPECIFIC PIECES OF INFORMATION THAT ARE LISTED IN THE FOA, IN THE FUNDING OPPORTUNITY ANNOUNCEMENT WE SAY ORWH IS SPECIFICALLY INTERESTED IN POTENTIAL APPLICATIONS THAT ADDRESS GENDER RESPONSIVE APPROACHES TO ACCOUNT FOR DIFFERENCES, ASSOCIATED WITH OPIOID USE DISORDER, EVIDENCE-BASED PRACTICES, TO ADDRESS GENDER SPECIFIC CONCERNS, AND GENDER-SPECIFIC APPROACHES TO ADDRESSING MENTAL HEALTH, REPRODUCTIVE AND SEXUALITY HEALTH OF WOMEN WITH OUD. I DRAW YOUR ATTENTION TO THE STRATEGY WHERE WE'RE INSERTING LANGUAGE AND FUNDING OPPORTUNITY ANNOUNCEMENT THAT INDICATE NIH'S COMMITMENT TO THESE ISSUES AS WELL AS OUR INTEREST AND OUR PARTNERSHIP WITH NIMHD. OPIOID USE ABUSE IS LINKED TO SCIENCE OF PAIN, THE NUMBER ONE REASON FOR PRESCRIPTION OF OPIOIDS. FEMALES AND WOMEN EXPERIENCE GREATER PAIN SENSITIVITY THAN MEN ACROSS EVERY PAIN MODALITY. FOR PRESSURE PAIN, ELECTRICAL AND COLD PAIN, WOMEN ARE MORE SENSITIVE IN ALL THOSE CATEGORIES. UNFORTUNATELY PRE-CLINICAL ANIMAL MODEL WORK THAT IS BEING DONE TO HELP US UNDERSTAND THAT IS STILL PREDOMINANTLY BEING DONE IN MALE RODENTS. SO THAT IS A PROBLEM AND A CLEAR MISMATCH, I WOULD SAY. ONE OF THE EFFORTS THAT NIH HAS UNDERTAKEN FOR SEVERAL YEARS AND ORWH PARTNERED WITH THE NIH PAIN CONSORTIUM IN ORDER TO ENHANCE COLLABORATION ACROSS THE DIFFERENT NIH INSTITUTES AND CENTERS AND OFFICES THAT CONDUCT RESEARCH ON PAIN IS THE PAIN CONSORTIUM. YOU CAN SEE ORWH HAS BEEN A PARTNER FOR SOME YEARS. I WANT TO BRING TO YOUR ATTENTION UPCOMING PAIN CONSORTIUM SYMPOSIUM IN MAY 31, ON MAY 31, AND THE KEYNOTE SPEAKER IS JUDITH PASTE FROM NORTHWESTERN SPEAKING ON, "FROM SCIENCE TO SOCIETY," AT THE INTERSECTION OF PAIN MANAGEMENT AND OPIOID CRISIS, I DRAW YOUR PETITION TO THAT OPPORTUNITY. I WANT TO SHARE WITH YOU THAT IT'S BEEN ORWH'S PRIVILEGE AND PLEASURE TO PARTICIPATE ALONG WITH OTHER ICOs ON THE CENTERS OF EXCELLENCE AND PAIN EDUCATION SOME VERY ON. YOU CAN SEE HERE ARE THE RECENT AWARDEES, I WANT TO SHARE WITH YOU I RECENTLY REVIEWED THE WEBSITE AND THEY HAVE PAIN INTERACTION MODULES INCLUDING MEN AND WOMEN WITH ATTENTION TO ISSUES RELATED TO SEX AND GENDER, ONE ON BURNING MOUTH COMMON SYNDROME COMMON IN SJOGREN'S, AND A MIGRAINE TREATMENT, I ENCOURAGE YOU TO TAKE A LOOK AT THOSE. INTEREST IN OPIOID CRISIS CLEARLY INVOLVES OUR OTHER FEDERAL PARTNERS, IMPORTANTLY OTHER FEDERAL PARTNERS ACROSS THE DEPARTMENT OF HEALTH AND HUMAN SERVICES. AND WE ARE DELIGHTED TO BE -- ASKED TO SERVE ON THE STEERING COMMITTEE FOR THE UPCOMING MEETING ON OPIOID AND NICOTINE USE, DEPENDENCE AND RECOVERY, BEING LED BY THE FDA'S OFFICE OF WOMEN'S HEALTH, BUT CDER AND CENTER FOR TOBACCO PRODUCTS ARE COLLABORATING, THAT'S COMING UP IN SEPTEMBER. THEY WILL BE EXPLORING INFLUENCES, INFLUENCE OF SEX AND GENDER, ACROSS HEALTH POLICY, RESEARCH, PROFESSIONAL EDUCATION AND CARE. SO THEY HAVE A HUGE AGENDA THERE. I DO WANT TO GIVE A SHOUT OUT TO MY COLLEAGUES, MARSHA HENDERSON AND MARJORIE JENKINS, AT THE OFFICE OF WOMEN'S HEALTH AT THE FDA FOR THEIR RECENT RESEARCH IMPACT IN OUTCOMES FRAMEWORK THAT THEY HAD POSTED ON THE WEBSITE FOR MEASURING IMPACT OF YOUR EFFORT. TAKE A LOOK AT THAT AS WELL. ANOTHER AREA WE'VE BEEN REALLY EXCITED ABOUT PARTNERING WITH AN INSTITUTE AND CENTER IS THE ABCD OR ADOLESCENT BRAIN COGNITIVE DEVELOPMENT STUDY, A HUGE STUDY BEING LED BY NIDA, THE LARGEST LONG TERM STUDY OF BRAIN DEVELOPMENT AND CHILD HEALTH IN THE UNITED STATES. THEY ARE COLLECTING INFORMATION ABOUT BOTH SEX AND GENDER, AND IN A RECENT PRESS RELEASE ORWH EFFORTS WERE SUCCESSFUL IN ENSURING THAT THIS INFORMATION WAS SHARED WITH THE PUBLIC THROUGH PRESS RELEASE. THE COMPREHENSIVE DATASET WILL BE DISAGGREGATED BY SEC, RACIAL GRUEL AND SES, ADDRESSING QUESTIONS RELATED TO ADOLESCENT& BRAIN DEVELOPMENT INCLUDING WHAT BRAIN PATHWAYS ARE ASSOCIATED WITH ONSET OF MENTAL HEALTH DISORDERS AND DO THEY DIFFER BY SEX, THIS IS WHERE WE CAN DEMONSTRATE CLEARLY CHANGES IN THE WAY THE INSTITUTES AND CENTERS ARE OPERATING BASED ON UPTAKE OF ABCD AND STAFF EFFORTS. EMPHASIZING SEX AND GENDER BASED REPORTING, HERE ARE A FEW OF RECENT ONES, HERE THE LANGUAGE INCLUDES REFERENCE ENSURE THAT APPLICATIONS MUST COMPLY WITH NIH POLICY ON REPORTING DISAGGREGATED SEX-BASED DATA AND OTHER CONSIDERATIONS OF SEX AS A BIOLOGICAL VARIABLE. THE QUESTION THAT IS POSED HAVE THE INVESTIGATORS IN THEIR APPLICATIONS OR IN THEIR PROGRESS REPORTS PRESENTED ADEQUATE PLANS TO ADDRESS RELEVANT BIOLOGICAL VARIABLES SUCH AS SEX FOR STUDIES IN VERTEBRATE ANIMALS AND HUMAN SUBJECTS, WHICH IS THE CORE OF SABV POLICY. AN ADDITIONAL AREA YOU'RE CONCERNED ABOUT IS TRAUMATIC BRAIN INJURY. IN FACT, NOTABLE IS THE FACT THAT TEENAGERS HAVE A SIGNIFICANT -- THIS IS A SIGNIFICANT IMPACT IN THAT POPULATION. I WANT TO DRAW YOUR ATTENTION TO SOME DATA THAT SURPRISED ME. IT'S A LITTLE HARD TO SEE. BUT THIS IS GIRLS SOCCER. THIS IS BOYS FOOTBALL. AND THIS IS THE REPORTED CONCUSSION AS A PROPORTION OF THE TOTAL INJURIES. YOU CAN SEE THAT GIRLS SOCCER EXCEEDS BOYS FOOTBALL, THIS IS HIGH SCHOOL. THAT WAS REALLY SURPRISING TO ME. CLEARLY INDICATING WE NEED TO HAVE ADDITIONAL ATTENTION IN THAT SPACE. AND SO I WILL GIVE A SHOUT OUT TO COLLEAGUES AT NINDS FOR ORGANIZING WORKSHOP ON TRAUMATIC BRAIN INJURY IN WOMEN. WE WERE PLEASED TO PARTNER WITH THEM ALONG WITH NICHD AND OTHERS FROM THE MILITARY, DR. PEG MCCARTHY GAVE THE KEYNOTE, UNIVERSITY OF MARYLAND, IDENTIFYING SEX DIFFERENCES IN RESEARCH, WHAT ARE THE CHALLENGES. AND WE HAD A SIGNIFICANT AGENDA HERE INCLUDING SPORTS-RELATED TBI, TBI AMONG SERVICE MEMBERS, TBI AS A CONSEQUENCE OF INTIMATE PARTNER VIOLENCE, AND OTHER IMPORTANT TOPICS. AND OF THE SPEAKERS, 21 OF THE SPEAKERS WERE WOMEN, 11 OF THE SPEAKERS WERE MEN, A SIGNIFICANT NUMBER, AND A LITTLE BIT OF A DIFFERENT PATTERN THAN YOU TYPICALLY SEE, EVEN AT NIH MEETINGS. AND SO WE WERE REALLY PLEASED TO SEE THAT. AND THE REPORT FROM THIS WORKSHOP WILL BE AVAILABLE SOON. SO STAY TUNED, YOU CAN ALWAYS GET THAT INFORMATION FROM OUR WEBSITE. ANOTHER EXAMPLE OF OUR PARTNERSHIPS WITH OUR INSTITUTES AND CENTER COLLEAGUES IS A RECENT COLLABORATION ON INCREASING UNDERSTANDING OF BASIC BIOLOGICAL PATHOPHYSIOLOGY AND BEHAVIOR MECHANISMS, THAT'S A LOT, LEADING TO BETTER HEALTH FOR FEMALE PATIENTS WITH LUNG DISEAS. KEYNOTES AT THAT EVENT WHERE WE COLLABORATED WITH THE LEADS FOR LUNG DISEASE, NIH, NHLBI, OFFICE OF RARE DISEASE RESEARCH NOW IN NCATS, DEBRA KLEGG FROM CEDARS-SINAI AND MARIANNE LEGATO. NOW A WEBINAR ON SEX AND GENDER DIFFERENCE TREATING ASTHMA, COPD AND INTERSTITIAL LUNG DISEASE WITH NIH MODERATOR, REGISTER HERE, THESE ARE EFFORTS OUT OF THAT NIH COLLABORATION. I'M GOING TO SHARE WITH YOU AS I ALWAYS DO AT THESE MEETINGS AN UPDATE ON OUR RESEARCH PROGRAMS. I DO WANT TO SHARE WITH YOU THE CONTEXT IN WHICH WE'RE OPERATING WHERE YOU CAN SEE FOR -- WE REALLY HAD SIGNIFICANT INCREASES IN OUR FUNDING FOR THE FIRST 12 OR 13 YEARS OF THE OFFICE. BUT HAVE NOT SINCE THAT TIME. AND WHEN I SHARE WITH YOU HOW WE'VE BEEN PARTNERING AND WHERE THE RESEARCH INVESTMENTS, YOUR TAXPAYER DOLLARS ARE GOING, FOR WOMEN'S HEALTH RESEARCH, THAT'S IMPORTANT TO KEEP IN MIND. YOU CAN SEE ON THE GRAPH HERE ORANGE AND YELLOW ARE FUNDS THAT ARE GOING DIRECTLY TO INSTITUTES AND CENTERS FOR THEIR PROGRAMS AND THAT RESEARCH, WHICH IS WOMEN'S HEALTH RESEARCH, SIGNIFICANT PROPORTION. 37% IN FY17. ALMOST A QUARTER OF OUR FUNDING GOES TO OUR OWN BIRCWH PROGRAM, AND OUR SCORE PROGRAM, 18%, TWO ADMINISTRATIVE SUPPLEMENTS PROGRAMS HERE AT 16 AND 5% FOR FY17, PROPORTIONS OF EXTRAMURAL BUDGE E AS BUDGET. THIS IS INFORMATION TO KEEP IN MIND AS WE GO FORWARD. LOOKING AT INSTITUTES AND CENTERS, IN TERMS OF ORWH DOLLARS AS EXTRAMURAL INVESTMENTS, YOU CAN SEE THE LEAD INSTITUTE GETTING MOST OF OUR FUNDING IS NICHD, FOLLOWED BY NIDA, NIDDK, THIS IS THE BIRCWH FUNDING, I'LL SHOW YOU A VIEW WITH BUNCH FUNDING REMOVED. STILL NICHED, IN MILLIONS HERE, AND NIDA, NIDDK ARE REALLY IN THE TOP RANK IN TERMS OF MOST OF OUR INVESTMENTS, BY WAY OF JUST REMINDER THESE INSTITUTES COME TO ORWH, FOLLOW A PROCESS WE DEVELOP AND ASK FOR ORWH FUNDING, CO-FUNDING, OF THEIR EFFORTS. THAT'S THE PROCESS INDICATING THERE. THAT'S THE DIRECTION OF THE ASK. NIAID, WHICH I'M PLEASED TO SEE HERE, ARE ROUNDING OUT THE SECOND CREW, AND ALL THE OTHER INSTITUTES AND CENTERS HERE WITH SOME DOWN AT THE END FOR FY17. IF YOU LOOK AT THE SEX AND GENDER ADMINISTRATIVE SUPPLEMENTS PROGRAM WHICH WE FOCUS ON, THIS IS CUMULATIVE DATA FOR FIVE YEARS THAT THIS PROGRAM HAS BEEN IN PLACE, YOU'LL SEE A LITTLE DIFFERENT PATTERN. NUMBER ONE HERE IS NINDS. AND I'M GOING TO GO BACK AND SHOW WHERE YOU NINDS WAS BEFORE, WHICH IS OVER HERE. RIGHT. AND SO CLEARLY NEUROSCIENCE ALSO HAS BEEN AN AREA THAT'S BEEN A LITTLE SLOWER ON THE UPTAKE OF SABV, WE THOUGHT IT CRITICALLY IMPORTANT TO HAVE TARGETED INVESTMENT. NIDA, NHLBI ON THE TOP, NIAMS, NIDDK AND AGING HERE IN THAT SECOND GROUP. AND YOU CAN SEE THE CUMULATIVE FUNDING FROM ORWH FOR THESE SEX AND GENDER ADMINISTRATIVE SUPPLEMENTS THAT LEVERAGED EXISTING NIH INVESTMENTS AND GAVE PIs AN TUNE TO LOOK AT SEX AND GENDER NEARLY $30 MILLION OVER THE LAST FIVE YEARS. AND FOR FY17, I'D LIKE TO SHOW YOU INVESTMENTS BY PROGRAM. HERE'S OUR SCORE. THESE ARE THE SIX ICs THAT ARE SUPPORTING THE SCORE, EXISTIN SCORE, 11 SCORE CENTERS, SIX OF THEM. 17 ICs I SHOWED YOU SUPPORTING SEX AND GENDER ADMINISTRATIVE SUPPLEMENTS. R56, BRIDGE GRANT. FIVE U 3 ADMINISTRATIVE SUPPLEMENTS, EIGHT AND THAT NUMBER HAS GONE UP FOR FY 18, OTHER IC CO-FUNDS, 16. YOU CAN SEE WE'RE REALLY COLLABORATING WITH NEARLY ALL OF THE INSTITUTES AND CENTERS, IN SOME WAY IN FY17 BY PROGRAM. I ALSO DO WANT TO DRAW YOUR ATTENTION TO THE FACT THAT THE NEW SCORE PROGRAM, SCORE WITH ANE AT AN E AT THE PROGRAM, IS THE ONLY ONE. THERE ARE A FEW SPECIFIC FUNDING ANNOUNCEMENTS THAT INSTITUTES AND CENTERS HAVE IN THEIR MISSION AREAS BUT THIS IS THE ONLY SEX DIFFERENCES DISEASE AGNOSTIC NIH FUNDING OPPORTUNITY, IN FY 18 REISSUED THAT AS SPECIALIZED CENTERS OF RESEARCH EXCELLENCE ON SEX DIFFERENCE AND WE MADE A FEW CHANGES. IT'S NOW A COOPERATIVE AGREEMENT, SO WE WENT FROM P50 TO U54, A CAREER ENHANCEMENT CORE REQUIRED FOR EVERY SCORE WITH AN E AT THE END, TO MEET CAREER ENHANCEMENT NEEDS IN THE STUDY OF SEX DIFFERENCE. EACH SCORE IS DESIGNED TO SERVE AS HUB FOR EDUCATION AND DISSEMINATION OF SIX-BASED RESEARCH METHODS AND BEST PRACTICES. IT'S A COOPERATIVE AGREEMENT, ICs PARTICIPATING IN THE FY 18 ISSUANCE, NIDDK, NIDA, N IEHS, NIMH, NIAAA, NIA, CLOSES ON APRIL 23. AND OUR OWN SCORE PI DR. SCOTT HOLDGREN WILL PRESENT LATER ON URINARY TRACT INFECTION, COMPLEXITY RESULTS FROM DIVERSITY, AT THE BACTERIAL HOST INTERFACE, WE'RE LOOKING FORWARD TO HEARING FROM SCOTT. U 3 STANDS FOR UNDERSTUDIES, UNDERREPRESENTED AND UNDER REPORTED POPULATIONS OF WOMEN, IN FQ 17 RECEIVED 27 APPLICATIONS FROM 11 INSTITUTES AND CENTERS, FUNDED 15 TO THE TUNE OF $1.7 MILLION, AND FY 18, 15 ICs SIGNED ON. ALMOST 100% INCREASE IN NUMBER FROM LAST YEAR; WE'LL MAKE AWARDS UP TO $200,000 IN TOTAL COST FOR FY 18, SO WE'RE EXCITED. WE'VE HAD INCREDIBLE INTEREST IN THIS PARTICULAR FUNDING OPPORTUNITY, JUST CLOSED EARLIER THIS WEEK, AND WE HAVE -- WE'LL BE LOOKING FORWARD TO SOME REALLY INCREDIBLE -- REVIEWING INCREDIBLE APPLICATIONS. I'D LIKE TO GIVE YOU A SHORT UPDATE ON SABV, A TOPIC NEAR AND DEAR TO OUR HEARTS. AND AS I WAS THINKING ABOUT THIS POLICY AND WHERE WE STARTED, YOU KNOW, LOTS OF WORK HAD BEEN DONE BY MANY, MANY PEOPLE IN THIS REALM BEFORE, BUT IT WAS CLEAR IN 2014 THAT THERE WOULD NEED TO BE A CHANGE IN HOW WE WERE OPERATING, IN ORDER TO MOVE FORWARD, AND SO BACK IN 2014 DR. COLLINS AND I PUBLISHED THIS PIECE IN "NATURE," SUBSEQUENTLY TWO GUIDE NOTICES CAME OUT, ONE ON ENHANCING REPRODUCIBILITY THROUGH RIGOR AND TRANSPARENCY, INCLUDING A SPECIFIC MENTION OF RELEVANT BIOLOGICAL VARIABLES SUCH AS SEX AND A SEPARATE GUIDE NOTICE JUST ON SABV INCLUDING ALSO A LINK OUT DOCUMENT TO MORE DETAILS. WE PUT AN RFI OUT TO GET INPUT FROM OUR STAKEHOLDERS AS WE WANTED TO INCLUDE THEM, FORMED THE TRANS-NIH SABV WORKING GROUP AND SET UP A RIGOR AND REPRODUCIBILITY MAILBOX THE POLICY WENT INTO EFFECT JANUARY 25, 2016, AND ORWH MEMBERS HAVE TIRELESSLY BEEN INTERACTING WITH THE INSTITUTES AND CENTERS AND OTHER COMMITTEES AND COUNCIL PRESENTING WHAT WE CALL ROAD SHOWS ABOUT SABV. WE ALSO OF COURSE HAVE PROVIDED A VARIETY OF OTHER TOOLS AND RESOURCES FOR OUR COLLEAGUES. FIRST WE HAD A METHODS WORKSHOP, HIGHLIGHTING WAYS TO INCREASE SABV INTO PRE-CLINICAL RESEARCH, SPECIFICALLY THAT INFORMATION AVAILABLE BY VIDEOCAST. WE ALSO THEN MORE RECENTLY HAD AN NIH SABV WORKSHOP IN COLLABORATION WITH THE OFFICE OF STRATEGIC COORDINATION, COMMON FUND, AND 21ST CENTURY CURES CAME OUT AND THERE'S LANGUAGE IN THAT ACT RELEVANT TO SABV. ALONG THE WAY WE ALSO HAVE BEEN PROVIDING WHAT I LIKE TO CALL GUIDEPOSTS IN TERMS OF PUBLICATION, FIRST HIGHLIGHTING SEX AS GUIDING PRINCIPLE, SECOND A PUBLICATION TALKING ABOUT SEX AND GENDER MAKING A SUGGESTION FOR HOW FOLKS MIGHT CONSIDER ALTERING HOW THEY DO THEIR TABLE ONE, INCLUDING BOTH, THEN THE PRE-CLINICAL METHODS WORKSHOP WAS PUBLISHED IN FASEB WITH SUPPLEMENTARY MATERIAL INCLUDING THREE SPECIFIC CASES AS TO HOW TO ADOPT SABV, AND THEN DR. LEGATO'S NEWEST JOURNAL, GENDER AND GENOME, DR. CORENELSON AND I PUBLISHED. JAMIE WHITE AND I PUBLISHED A PIECE, AND PHYSIOLOGY AND BEHAVIOR PUBLISHED A PIECE BASED ON -- LET ME GO BACK ONE THING TO SHARE WITH YOU, BASED ON PRESENTATION AT AMERICAN UNIVERSITY. ALSO THE TRANS-NIH SABV WORKING GROUP HAS BEEN WORKING TIRELESSLY TO PROVIDE NEW FAQs BASED ON INPUT AND QUERIES THAT WE RECEIVED FROM THE PUBLIC, FROM THE SCIENTIFIC COMMUNITY AS WELL AS OUR NIH COLLEAGUES WHO SAY THIS ISN'T CLEAR, WE HAVE A QUESTION, CAN YOU IMPROVE HOW YOU'RE ANSWERING THIS SO WE ALL UNDERSTAND WHAT IS EXPECTED. SO WE'VE CERTAINLY, I WOULD SAY, PLAYED A CRITICAL ROLE IN THE DEVELOPMENT OF THESE SABV RESOURCES AND ACTIVITIES, ALWAYS IN PARTNERSHIP WITH OUR INSTITUTE AND CENTER COLLEAGUES, AND I DRAW YOUR ATTENTION TO A COUPLE OF THOSE RESOURCES AND I WANT TO ASK FOR YOUR HELP IN DISSEMINATING THAT TO YOUR CONSTITUENTS BECAUSE PEOPLE DON'T KNOW THEY EXIST, FIRST WITH THE OFFICE OF EXTRAMURAL RESEARCH, DESIGNED FOR REVIEWERS TO HELP THEM THINK ABOUT HOW TO START ASSESSING WHETHER AN APPLICATION HAS ADEQUATELY ADDRESSED SEX AS A BIOLOGICAL VARIABLE. THE SECOND IS A CHECKLIST THAT WAS DESIGNED FOR RESEARCHERS TO USE AS THEY THINK ABOUT DEVELOPING A STUDY STARTING WITH CONSIDERING THE INFLUENCE OF SEX WHEN YOU'RE ACTUALLY FORMULATING YOUR RESEARCH QUESTION. AND THEN ALL THE WAY DOWN TO COMMUNICATING APPROPRIATELY ABOUT YOUR FINDINGS IN TERMS OF THE LIMITATIONS IN TERMS OF GENERALIZABILITY, BASED ON WHETHER YOU ARE INCLUDING MALES AND FEMALES, HOW MALES AND FEMALES MIGHT HAVE BEEN ADDRESSED IN YOUR STUDY DESIGN. WE ALSO HAVE LOOKED AT OTHER WAYS TO DISSEMINATE INFORMATION ABOUT THE SEX AS A BIOLOGICAL VARIABLE POLICY. FIRST I WANT TO HIGHLIGHT THE FACT WE RELAUNCHED THE NIH WOMEN'S HEALTH RESEARCH SEMINAR SERIES WITH THIS IN MIND. THE FIRST OF THOSE WAS IN DECEMBER, WHERE WE FOCUSED ON PAIN AS A TOPIC. DR. MOGUL PRESENTED ON PAIN, SEX AND DEATH. DR. FILLINGHAM AND OTHERS ON OTHER TOPICS. WE CHOSE PAIN AS A CRITICALLY IMPORTANT TOPIC, THREE OR FOUR DIFFERENT PRESENTATIONS AVAILABLE BY VIDEOCAST, DR. SABERKLEIN TALKED ABOUT SEX DIFFERENCE IN VACCINE EFFICACY, AND IN JUNE WE'RE LOOKING FORWARD TO AN INCREDIBLE SPECIAL PRESENTATION BY DR. LANGER WHO IS HERE, DR. GOLDSTEIN, VIRGINIA MILLER AND DR. COOK FROM NHLBI CONNECTING THE HEART AND THE BRAIN IN THE CONTEXT OF HEALTH OF WOMEN. WE ALSO FOUNDED A NEW SCIENTIFIC INTEREST GROUP THAT IS A WAY TO DISSEMINATE AND TALK ABOUT THE APPLICATION OF SABV TO SPECIFIC SCIENTIFIC AREAS, THE FIRST SCIENTIFIC INTEREST GROUP PRESENTATION BY DR. ARMAND RASNAHAN USING NEURAL IMAGING FOLLOWED BY A PRESENTATION ON SEXUAL DIMORPHISM AND DNA METHYLATION AS A MODIFIER OF PREDISPOSITION TO HUMAN DISEASE, BY ANA MINOVA FROM McGILL AND IN MAY CONNECTIONS BETWEEN SLEEP PATTERNS AND GENE NETWORKS IN FRUIT FLIES FROM NHLBI'S SUSAN HARBESON, ANOTHER STRATEGY WE'VE USED. NIH-- I MEAN ORWH COLLEAGUES HAVE BEEN TIRELESSLY PRESENTING ON SABV AND RELATED TOPICS AT A WIDE VARIETY OF SCIENTIFIC FORUMS INCLUDING THE AMERICAN COLLEGE OF LABORATORY AND ANIMAL MEDICINE, THE PRIMATE RESEARCH CENTERS, MAYO CLINIC, AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY, AND SSN. THEY HAVE BEEN VERY, VERY BUSY. WE PARTNERED WITH OFFICE OF STRATEGIC COORDINATION WHO MANAGES COMMON FUND TO HOST THE FIRST SABV WORKSHOP IN OCTOBER, AND THE KEYNOTE SPEAKER WAS DR. VIRGINIA MILLER. THE VIDEOCASTS ARE AVAILABLE FROM BOTH DAY 1 AND DAY 2. THERE WAS A POSTER SESSION. YOU CAN SEE THE RANGE OF TOPICS THAT WERE PRESENTED. I WANT TO DRAW YOUR ATTENTION SPECIFICALLY TO TWO. SEX DIFFERENCES IN ANIMAL MODELS AND SEX DIFFERENCES IN GENE EXPRESSION. THAT INFORMATION IS AVAILABLE IN THE VIDEOCAST AND WE ARE SEEING CONTINUED UPTAKE OF VIEWS OF BOTH DAY 1 AND DAY 2. ANOTHER RESOURCE THAT I'D LIKE YOUR ASSISTANCE WITH DISSEMINATING TO YOUR COLLEAGUES IN TERMS OF OPPORTUNITIES TO HEAR ABOUT THE FIRST WAYS OF SABV BEING ADDRESSED, MOST OF THE SPEAKERS WERE PRINCIPAL INVESTIGATORS WHO RECEIVED THE SUPPLEMENT WITH RESEARCHERS AS WELL. SO, I'M NOT A SAILOR, BUT I CAN TELL WHEN THE LANDSCAPE IS CHANGING. IT'S IMPORTANT TO READ THOSE WINDS. I'M NOT A GOLFER, I DO PLAY TENNIS, YOU NEED TO KNOW WHICH DIRECTION THE WIND IS GOING WHEN SERVING. AND SO IT'S ALWAYS IMPORTANT TO KNOW WHERE YOU'RE OPERATING AND ADJUSTING YOUR COURSE, ACCORDINGLY. AND THE 21ST CENTURY CURES ACT IS ONE OF THOSE COURSE CHANGERS THAT I THINK IS IMPORTANT TO ACKNOWLEDGE. PARIS WATSON, OUR LEGISLATIVE POLICY ANALYST, WILL BE GIVING YOU A FULL LEGISLATIVE AND 21ST CENTURY CURES UPDATE, SO LOOK FORWARD TO HEARING THERE. OF COURSE, SCIENCE MOVES FORWARD. WE HAVE ADVANCES IN SCIENCE AND TECHNOLOGY. WE HAVE CRISPR/CAS9, NEW IMAGING MODALITIES, WE WANT TO BE ABLE TO TAKE ADVANTAGE OF THOSE ADVANCES AS WELL. AND WE ALSO HAVE CHANGES IN OUR PUBLIC HEALTH LANDSCAPE. AND WE NEED TO BE ADDRESSING THOSE PUBLIC HEALTH NEEDS. AND THIS IS ONE THAT I REALLY AM DISTURBED BY. THIS IS MATERNAL MORTALITY WHICH CONTINUES TO RISE IN THE UNITED STATES, EVEN AS IT DECLINES IN OUR PEER COUNTRIES. AND THIS IS REALLY UNACCEPTABLE. AND DISTURBING. AND I'M GOING TO PUT A FACE ON THAT STORY. I WANT TO SHARE VERY BRIEFLY THE STORY OF DR. IRVING, WHO WAS A CDC EPIDEMIOLOGIST WORKING ON HEALTH DISPARITIES RESEARCH. SHE WAS A LIEUTENANT COMMANDER IN THE COMMISSION CORPS, HAD TWO MASTER'S DEGREES, HAD A DUAL SUBJECT Ph.D., AND SHE DIED AT THE AGE OF 36 FROM PREGNANCY-INDUCED COMPLICATIONS. SHE HAD EXCELLENT INSURANCE. SHE HAD EXCELLENT PRENATAL CARE, OUTSTANDING SUPPORT FROM FAMILY MEMBERS AND COLLEAGUES AT WORK. THIS SHOULDN'T BE HAPPENING. WE HAVE TO FIND A WAY TO ADDRESS THESE ISSUES. YOU'RE GOING TO HEAR MORE ABOUT THAT A LITTLE BIT LATER. IT'S ALSO NOT JUST WOMEN WHO ARE DYING. AND THIS IS A SHIFT IN TOPIC HERE. THIS IS A DIFFERENT BUT RELATED TOPIC, CLEARLY WE'RE HAVING CONCERNS WITH MATERNAL HEALTH. WE'RE HAVING INCREASES IN MATERNAL OPIOID USE, AND INCREASES IN BABIES BEING BORN WITH OPIOID WITHDRAWAL SYMPTOMS. YOU'LL HEAR FROM DR. DIANA BIANCHI, DIRECTOR OF EUNICE KENNEDY SHRIVER ON CHILD HEALTH AND DEVELOPMENT, A PEDIATRICIAN, PREGNANT AND LACTATING WOMEN IN RESEARCH, INCLUDING IN PRESENTATION A REALLY INTERESTING STRATEGY NICHD EMPLOYED WITH MULTIPLE PARTNERS ON CROWD SOURCING FOR GETTING INFORMATION ABOUT PREGNANCY, PREGSOURCE IS THE NAME OF THAT PROGRAM. SO AS YOU'RE OPERATING IN ANY KIND OF OPEN WATERS, IT'S IMPORTANT TO KIND OF KEEP YOUR EYE ON THE HORIZON AND WHERE YOU'RE GOING. AND ONE OF THE THINGS THAT WE CONSIDERED IN THESE CHANGING TIMES IS WHERE IS OUR TRUE NORTH, WHAT IS OUR VISION, WHERE ARE WE TRYING TO GO, WHAT IS THE WORLD WE WANT TO SEE, WE ENVISION WHERE SEX AND GENDER DIFFERENCE ARE INTEGRATED INTO BIOMEDICAL RESEARCH, EVERY WOMAN RECEIVES TREATMENT TAILORED TO HER NEEDS, CIRCUMSTANCES AND GOALS. AND A PLACE AND WORLD WHERE WOMEN IN SCIENCE REACH THEIR FULL POTENTIAL. AND SO WE HAD NOT ARTICULATED THAT VISION IN THE PAST, I WANTED TO SHARE IT WITH YOU TODAY. AND DR. MARGARET BEVANS, ASSOCIATE DIRECTOR FOR CLINICAL RESEARCH ATORWH, ARE GIVE AN UPDATE ON THE STRATEGIC PLAN FOR RESEARCH ON WOMEN'S HEALTH LATER TODAY WHERE YOU'LL HEAR HOW WE'D LIKE TO MOVE FORWARD IN ACHIEVING I ACHIEVING THIS VISION. I'D LIKE TO SHARE UPDATES ON WOMEN IN BIOMEDICAL CAREERS. I'M CLOSE TO THE END HERE. I WANT TO MAKE SURE WE HAVE TIME FOR ALL OUR OTHER AMAZING PRESENTATIONS. I CONTINUE TO CO-CHAIR THAT WORKING GROUP WITH DR. COLLINS. AS YOU KNOW, THAT WORKING GROUP WAS PART OF THE IMPETUS FOR CAUSAL FACTORS IN INTERVENTION, FUNDING OPPORTUNITY ANNOUNCEMENT THAT FUNDED 14 GRANTS AT THE TUNE OF $16.8 MILLION FROM 11 ICs, FOUR OFFICES. WE'RE LOOKING AT THE OUTCOME OF THAT PARTICULAR FUNDING OPPORTUNITY, OVER 100 PUBLICATIONS HAVE RESULTED, MANY OF THOSE P.I.s HAVE GONE ON TO GET ADDITIONAL FUNDING. SO WE'RE PARTICULARLY PLEASED TO SEE THAT. ONE OF THE EFFORTS OF THE WORKING GROUP IS THE WOMEN OF COLOR RESEARCH NETWORK, WHICH HAS SEVERAL REGIONAL CHAPTERS AND IS NOW AVAILABLE ON LINKED IN, AND I WANT TO SHARE WITH YOU THAT DR. SHIRLEY MALCOLM, WELL KNOWN TO ALL OF YOU HERE, CAME TO TALK TO BOTH DR. COLLINS, MYSELF AS WELL, AS THE ENTIRE WORKING GROUP, OH AN EFFORT, C CHANGE SCIENCE, TECHNOLOGY, MATHEMATICS, EQUITY ACHIEVEMENT PROJECT PROGRAM, A PILOT PROGRAM FOR INSTITUTIONS TO VOLUNTEER TO COLLECT DATA ON DIVERSITY OF EFFORTS, THAT GOALS AND DEVELOP ACTION PLANS FOR IMPROVING RECRUITMENT, HIRING AND RETENTION OF DIVERSE STUDENTS, PHAK FACULTY, LEADERSHIP IN WOMEN, ESSENTIALLY AN ASSESSMENT AND CERTIFICATION PROGRAM BUILT UPON MODEL ESTABLISHED BY ADINA SWANN, ADOPTED IN THE U.K. AND AUSTRALIA TO CREATE INSTITUTIONAL CHANGE TO FOSTER DIVERSITY IN S.T.E.M. WE'RE VERY EXCITED TO HEAR ABOUT IT, AND I HOPE WE'LL HAVE MORE TO SHARE IN THE FUTURE. OUR SPECIFIC EFFORTS IN THIS CASE, WE'VE DEVELOPED PEARLS OF WISDOM VIDEO SERIES, THE FIRST SET DEVELOPED IN PARTNERSHIP WITH THE NATIONAL MEDICAL ASSOCIATION AND FEATURE WOMEN OF COLOR. THERE'S SEVEN MORE VIDEOS IN ADDITION TO THESE THAT YOU SEE HERE. AND I WAS PLEASED TO RECENTLY SPEAK AT UNIVERSITY OF PENNSYLVANIA ON THE INVITATION OF DR. EVE HIBBENBOTHAM IN HEALTH EQUITY WEEK. YOU'LL SEE MORE PEARLS OF WISDOM AS WE MOVE FORWARD INTO THE NIH REALM, MEN AND WOMEN LEADERS TALKING ABOUT ADVANCING WOMEN IN S.T.E.M. SOON. TOPIC WE SELECTED THIS YEAR FOR THE THIRD ANNUAL SYMPOSIUM IS LEVERAGING THE NETWORK TO ADVANCE WOMEN IN SCIENCE, THIS INCLUDES LEVERAGING THE NETWORK WITH WOMEN AND MEN TO ADVANCE WOMEN IN SCIENCE. DR. PENN WILL GIVE OPENING REMARKS, DR. KAY LUND WILL SPEAK ON ADVANCING WOMEN IN THE NIH BIOMEDICAL RESEARCH WORK FORCE THROUGH MENTORING, DR. FORD FROM HOPKINS WILL TALK ABOUT ACHIEVING ADVANCED LEADERSHIP POSITIONS FOR WOMEN IN ACADEMIA, DR. HELLER ADVANCING WOMEN IN STEM, AND AWIS CEO, AND A SPEED NETWORKING SESSION WE'RE CALLING CATALYTIC CONNECTIONS. TAKE A LOOK AT THE WEBSITE, THERE'S STILL TIME TO REGISTER FOR THAT. I'LL ROUND OUT MY PRESENTATION WITH A FEW OTHER ORWH ACTIVITIES ABOUT WHICH I THINK YOU NEED TO BE AWARE, AND THAT IS AMAZING WORK BEING DONE BY ORWH TEAM MEMBERS. I WANT TO ACKNOWLEDGE DR. ARNEGAR, BEG AND SERANO, WHO HAD RECENT PUBLICATIONS, ALL IMPORTANT TOPICS. CONGRATULATIONS TO THEM. AND I WANT TO ALSO SHARE WITH YOU OUR SPECIFIC AND STRATEGIC STRATEGY AROUND STAKEHOLDER ENGAGEMENT HAS YIELDED SIGNIFICANT RETURNS. WE HAVE BEEN IN THIS SPACE, MARTY BOND, CHIEF OF PUBLIC AFFAIRS, LEADING US IN THAT EFFORT WITH PROFESSIONAL ORGANIZATIONS, ACADEMIA AND OTHERS, WITH THE GOAL OF AMPLIFYING OUR MESSAGE, ENHANCING OUTPUT AND GETTING TARGETED OUTREACH. THERE ARE CURRENTLY 1100 STAKEHOLDERS IN OUR SYSTEM THAT WE'RE REACHING, WE HAVE 25 KEY STAKEHOLDERS THAT WE ARE TRYING TO REACH AS WELL. AND OVER -- LET ME SHARE WITH YOU A COUPLE OTHER PIECES OF INFORMATION. FORTUNATE TO BE ABLE TO REACH OVER 30,000 MEMBERS OF THE APHA THROUGH A STRATEGIC PARTNERSHIP WITH DR. BENJAMIN, EXECUTIVE DIRECTOR OF APHA, AND THE WAY THIS IS PLAYED OUT THROUGH THE STRATEGIC PARTNERSHIPS WE HAVE SEEN ENHANCED INPUT, FOR EXAMPLE YOU'LL HEAR FROM DR. BEVANS ABOUT INPUT FROM THE RFI, A LARGE NUMBER OF RESULTS. SO WE'RE PLEASED ABOUT THAT STAKEHOLDER ENGAGEMENT. AND WE HAVE ALSO MADE A FEW OTHER CHANGES THAT MIRROR THE APPROACH THAT WE'RE USING AT NIH AND ORWH IN TERMS OF HIGHLIGHTING THE OFFICE OF RESEARCH ON WOMEN'S HEALTH EFFORTS IN THE CONTEXT OF SPOTLIGHTING THE INSTITUTES AND CENTERS' EFFORTS. THE AMAZING WORKS THEY ARE FUNDING IN THE WOMEN'S HEALTH RESEARCH REALM. AND SO WE HAVE A WOMEN'S HEALTH IN FOCUS IS THE TITLE OF OUR NEW NEWSLETTER, WITH FEATURE STORIES, INCLUDING IN THIS CASE PARTICULAR STORY ON MENTAL ILLNESS, CONNECTION WITH CHRONIC DISEASES. AS WELL AS AN SABV COLUMN. WE TALKED ABOUT PAPERS THAT ARE IN THE JOURNALS. ALL OF THE MATERIAL THAT HAD BEEN ON WOMEN IN SCIENCE CAREERS, ADVANCES AND INSIGHT NEWSLETTER INCLUDED IN WOMEN AND SCIENCE SECTION. ANY FUNDING OPPORTUNITIES AND OTHERS ARE AVAILABLE. SO I WANT TO DRAW YOUR ATTENTION TO THAT. THE NEXT ISSUE WILL FOCUS ON THE MICROBIOME AND HEALTH OF WOMEN, INCREDIBLE TOPIC. IF YOU'D LIKE TO RECEIVE THIS, MORE LIKE AN ONLINE MAGAZINE, PLEASE E-MAIL US AT ORWHINFO@NIH.GOV. SUBJECT LINE SUBSCRIBE ME. YOU'LL HEAR MORE ABOUT THE PROGRAMS. OUR AMAZING COMMUNICATIONS TEAM LED BY LAMONT WILLIAMS LED US TO REDESIGN THE WEBSITE TO FUNCTION AS MORE OF A WAY TO PROVIDE BOTH HIGH LEVEL INFORMATION, ALL ORWH RESOURCES ARE THERE INCLUDING A-Z GUIDE ON SEX AND GENDER INFLUENCE ON HEALTH AND DISEASE, WOMEN OF COLOR HEALTH DATA BOOK, FUNDING OPPORTUNITIES, BUT THERE'S ALSO A SPECIFIC LINK THAT GETS YOU TO EVERY SINGLE INDIVIDUAL INSTITUTE AND CENTER'S WOMEN'S HEALTH RESEARCH RELEVANT CONTENT. YOU CAN GET TO ALL OF THAT CONTENT THROUGH THE ORWH WEBSITE THAT NOW FUNCTIONS AS A PORTAL. THE NEWSLETTER, WEB SITE AND SOCIAL MEDIA ARE ORGANIZED TO ENCOURAGE WORK BEING DONE BY AMAZING 27 INSTITUTES AND CENTERS AND ALL THE OFFICES SO WE CAN SEE THAT THE WHOLE TRULY IS GREATER THAN THE SUM OF THE PARTS AND WE'RE TRYING TO FACILITATE THAT RECOGNITION. WE AMPLIFY MESSAGES VIA SOCIAL MEDIA AS DOES EVERYONE. WE HAVE 2500 NEW TWITTER FOLLOWERS, I'M PLEASED TO SHARE WITH YOU THAT WE ALSO HAVE 500 NEW FACEBOOK FANS, SIGNIFICANT MEDIA MAINSTREAM MENTIONS IN THE LAST YEAR, 26, A FAIRLY NEW SPACE FOR ORWH. ALSO IN THE UPCOMING WOMEN'S HEALTH CONFERENCE SPONSORED BY ACADEMY OF WOMEN'S HEALTH ORWH WILL BE HAVING A PRE-CONFERENCE WORKSHOP THAT IS FREE OF CHARGE. ADDRESSING HEALTH CHALLENGES OF WOMEN ACROSS THE LIFE COURSE IS THE TITLE, A NOVEL AND EMERGING RESERVE, KARA HALL IS PRESENTING ON TEAM SCIENCE, YOU CAN STILL REGISTER THROUGH OUR WEBSITE. IT'S ON MAY 3, AGAIN FREE OF CHARGE. I ENCOURAGE YOU TO TAKE A LOOK AT OUR WEBSITE, CONNECT WITH US, ALL THESE DIFFERENT WAYS THAT YOU CAN. I LOOK FORWARD TO THE REST OF OUR MEETING. THANK YOU SO MUCH FOR YOUR ATTENTION. I HOPEFULLY DIDN'T GO TOO MUCH OVER. [APPLAUSE] I'M GOING TO COME OVER TO THE OTHER SIDE THERE AND MAKE SURE WE ARE CUED UP FOR THE NEXT PRESENTATION. IN THE INTEREST OF TIME I'M GOING TO GO RIGHT TO MISS PARIS WATSON'S PRESENTATION. I'M SURE WE'LL HAVE TIME LATER IN THE DAY TO DISCUSS ANY QUESTIONS, SO PLEASE JOT THEM DOWN, MEMBERS, SO YOU'LL REMEMBER YOUR QUESTIONS AND WE CAN TALK ABOUT THEM LATER. SO WITHOUT FURTHER ADO, PARIS WATSON. >> GOOD MORNING. I AM PLEASED TO TALK TO YOU TODAY ABOUT 21ST CENTURY CURES. I'M PARIS WATSON, AS DR. CLAYTON MENTIONED, A LEGISLATIVE POLICY ANALYST AT ORWH. A YEAR AGO, A LITTLE OVER A YEAR AGO, THEN-PRESIDENT BARACK OBAMA SIGNED THE 21ST CENTURY CURES ACT INTO LAW, AND IT SEEMS LIKE A REALLY GOOD TIME TO TAKE A STEP BACK, LOOK AT THE 21ST CENTURY CURES AND HOW IT HAS IMPACTED NOT JUST NIH BUT ORWH AND THE WORK THAT WE DO. THERE ARE THREE MAIN GOALS OF THE LEGISLATION, TO ENHANCE RESEARCH, ENSURE TREATMENTS ARE ASSESSED BY PATIENTS MORE QUICKLY, AND INVESTING IN MEDICAL INNOVATION, PROTECTING AND CREATING JOBS IN THE U.S. 21ST CENTURY CURES RESULTED IN AN INVESTMENT IN THE NIH INNOVATION FUND, AND PROVIDED RESOURCES SPECIFICALLY FOR FOUR INITIATIVES. PRECISION MEDICINE, CANCER MOONSHOT, REGENERATIVE MEDICINE. YOU CAN SEE FUNDING VARIES OVER THE COURSE OF TEN YEARS. WE AT ORWH BENEFIT FROM THIS INFUSION OF RESOURCES BECAUSE WOMEN'S HEALTH RESEARCH AND POLICIES LIKE SABV APPLY THROUGHOUT THE WORK OF NIH. WHILE THERE AREN'T IC-SPECIFIC FUNDING, OUR WORK IS ENHANCED THROUGH WORK IN THESE FOUR AREAS. 21ST CENTURY CURES ALSO REAFFIRMED COMMITMENT TO INCLUSION, AND WE SEE IMPORTANCE OF THE HEALTH OF WOMEN THROUGHOUT THE LEGISLATION. NOT ONLY DOES THE LEGISLATION MANDATE COLLECTION OF DATA ON WOMEN, MINORITIES, AND INCLUSION ACROSS THE LIFESPAN IN CLINICAL RESEARCH, BUT THERE'S AN INVESTMENT IN DIVERSE WORKFORCE BY RAISING THE NIH'S STUDENT LOAN REPAYMENT CAPS TO $50,000 A YEAR. THE 21ST CENTURY CURES AS I SAID HAS IMPACTED NIH, ORWH, AND WOMEN'S HEALTH. AS YOU'LL SEE SHORTLY WHEN I TALK ABOUT THESE FOUR AREAS, WE HAVE NEW REPORTING REQUIREMENTS, THERE ARE NEW POLICIES, AND THERE ARE MANDATED CHECK-INS BETWEEN THE DIFFERENT INSTITUTES AND CENTERS AND OUR OFFICE AROUND THEIR STRATEGIC PLANS. MUCH HAS BEEN LEARNED ABOUT HOW SEX AND RACE MAY CONTRIBUTE TO DIFFERENCES IN HEALTH OUTCOMES AND PHYSIOLOGIC CONDITIONS. WE KNOW, FOR EXAMPLE, THAT AFRICAN-AMERICANS WITH HYPERTENSION ARE MORE SUSCEPTIBLE TO STROKES THAN WHITES WITH THE SAME BLOOD PRESSURE LEVELS. NIH HAS AMENDED THE INCLUSION POLICY TO ENHANCE PUBLIC REPORTING OF SEX AND GENDER, ETHNICITY INCLUSION DATA WITH BACKING FROM THE 21ST CENTURY CURES ACT, THIS AMENDMENT SPECIFICALLY REQUIRES THE RESULTS OF VALID ANALYSIS ON SEX GENDER AND RACE/ETHNICITY TO clinicaltrials.gov AFTER COMPLETING NIH DEFINED PHASE 3 CLINICAL TRIAL. VALID ANALYSIS REFERS TO STRATIFIED ANALYSES THAT EXPLORE HOW WELL INTERVENTION WORKS AMONG SEX/GENDER AND RACIAL AND ETHNIC GROUPS, MAY OR MAY BE POWERED STUDIES CAN STILL SHED LIGHT ON TRENDS AFFECTING DIRECTION OF FUTURE RESEARCH QUESTIONS. APPLICABLE CLINICAL TRIALS IN GENERAL STUDY FOOD AND DRUG ADMINISTRATION REGULATED THERAPEUTICS, BIOLOGICS AND DEVICES. THE REPORTING REQUIREMENTS SPECIFIC LEGISLATION REFERS TO IS NIH-DEFINED PHASE 3 CLINICAL TRIALS, WHICH ARE STUDIES THAT EVALUATE INTERVENTION IN LARGE GROUPS OF PEOPLE BY COMPARING INTERVENTION TO OTHER STANDARDS OR EXPERIMENTAL INTERVENTIONS. NIH FUNDS ABOUT 600 OF THESE TYPES OF TRIALS EACH YEAR. CLINICAL RESEARCH ACROSS THE LIFESPAN IS ESPECIALLY IMPORTANT FOR DISEASES SUCH AS CARDIOVASCULAR DISEASE WHICH HAS AN ONSET IN WOMEN AT OLDER AGE THAN IN MEN. SO CLINICAL TRIAL HAS ARBITRARY AGE CUTOFF OF 70, MAY NOT PICK UP CARDIOVASCULAR DISEASE IN WOMEN. WITH THE INCLUSION ACROSS THE LIFESPAN POLICY, NIH AIMS TO ENSURE INDIVIDUALS ARE INCLUDED IN CLINICAL RESEARCH IN A MANNER APPROPRIATE TO THE SCIENTIFIC QUESTION UNDER STUDY SO KNOWLEDGE IS GAINED FROM NIH-FUNDED RESEARCH, APPLICABLE TO ALL THOSE AFFECTED BY THE RESEARCHED DISEASES AND CONDITIONS. POLICY EXPANDS THE INCLUSION OF CHILDREN AS PARTICIPANTS IN CLINICAL RESEARCH POLICY TO INCLUDE ALL AGES. THE POLICY ALSO CLARIFIES POTENTIAL JUSTIFICATIONS FOR AGE-BASED EXCLUSION CRITERIA AND REQUIRES PARTICIPANT AGE AT ENROLLMENT TO BE PROVIDED IN PROGRESS REPORTS. FINALLY, THE 21ST CENTURY CURES ACT PROVIDES SUPPORT FOR COORDINATION BETWEEN THE INSTITUTES, CENTERS AND OFFICE, AND ORWH. BECAUSE OF THIS LEGISLATION, OUR COORDINATING COMMITTEE, THE CCRWH, IS NOW COMPRISED OF THE DIRECTORS OF THE DIFFERENT ICOs, OR THEIR SENIOR LEVEL STAFF DESIGNEE. ADDITIONALLY, THE DIRECTORS OF THE VARIOUS INSTITUTES, CENTERS AND OFFICES ARE NOW MANDATED TO CONSULT WITH THE ORWH DIRECTOR ANNUALLY TO DISCUSS HOW THEIR OBJECTIVES TAKE INTO ACCOUNT WOMEN AND ARE FOCUSED ON REDUCING HEALTH DISPARITIES. ADDITIONAL IC STRATEGIC PLANS MUST NOW INCLUDE DETAILS ON THESE OBJECTIVES. WE ARE VERY PLEASED WITH THE FOCUS ON THE HEALTH OF WOMEN IN 21ST CENTURY CURES, AND WE LOOK FORWARD TO WORKING WITH OUR ICO PARTNERS IN THE IMPLEMENTATION OF MANY OF ITS PROVISIONS. THANK YOU. [APPLAUSE] >> BECAUSE MISS WATSON WAS SO EFFICIENT, WE'RE BACK ON TIME. I WAS NOT EFFICIENT. THANK YOU, PARIS. >> YOU'RE WELCOME. >> ARE WE ABLE TO ASK QUESTIONS? >> ABSOLUTELY. WE CAN TAKE A COUPLE QUESTIONS WHILE WE HAVE DR. MARGARET BEVANS COME. I'LL TAKE ONE OR TWO QUESTIONS, MARGARET, SINCE WE GOT A LITTLE BIT OF TIME. >> CLARIFYING QUESTION. WITH THE DIFFERENT REQUIREMENTS ON BOTH THE VALID ANALYSES AND CLINICAL TRIALS AS WELL AS PARTICULARLY ONES ON THE COORDINATING COMMITTEE AND CONSULTING, ARE THOSE IN EFFECT CURRENTLY, OR DID THEY GIVE LIKE A ONE-YEAR -- ANY DEADLINES, LIKE ARE THESE IMPLEMENTED NOW? >> THE FIRST QUESTION REGARDING THE REQUIREMENTS THAT THOSE THAT CONDUCT NIH-BASED NIH-DEFINED PHASE 3 APPLICABLE CLINICAL TRIALS REPORT THEIR RESULTS FOR VALID ANALYSIS FOR THE DIFFERENCE IN PRIMARY OUTCOME BY SEX/GENDER, RACE/ETHNICITY APPLIED AFTER 2015. REGARDING CCRWH CHANGES THAT IN EFFECT, AND WE PLAN TO BE HAVING THE FIRST MEETING OF THE NEWLY RECONSTITUTED CCRWH IN JUNE OF THIS YEAR, DR. COLLINS DID SPEAK TO ALL THE INSTITUTE AND CENTER DIRECTORS AT A MEETING TRANSMITTING THIS INFORMATION, AND SENIOR LEVEL DESIGNEES HAVE BEEN PROVIDED BY EACH OF THE ICs. SO THAT'S IN EFFECT NOW. FULLY OTHER QUICK QUESTIONS BEFORE DR. BEVANS? DR. GREEN? >> SO GREAT PRESENTATIONS FROM BOTH OF YOU, AND CONGRATULATIONS TO PARIS WHO IS GETTING READY TO GRADUATE WITH HER MASTER'S. MY QUESTION REALLY FOCUSES ON YOU'VE GOT $4.8 BILLION GOING TO THE MOONSHOT, PRECISION MEDICINE. HOW DO WE KNOW THAT THE WORK IS NOT JUST REPRESENTATIONAL IN REGARDS TO WOMEN'S HEALTH AND THAT WE'RE ACTUALLY TAKING INTO CONTEXT THE WHOLE WOMAN? >> SO AS USUAL, DR. GREEN, YOU GET STRAIGHT TO THE POINT, THE HEART OF THE MATTER. I APPRECIATE THAT. THE FUNDING THAT CAME FROM 21ST CENTURY CURES IS NOT IC SPECIFIC. IT IS DISEASE AGNOSTIC, EXCEPT FOR THE CANCER MOONSHOT. HOWEVER, ALL OF THAT FUNDING, THE APPLICATIONS THAT COME THROUGH FOR THAT, ARE SUBJECT TO NIH POLICY. THAT MEANS IF THEY INVOLVE VERTEBRATE ANIMALS AND HUMANS, WHICH ODDS ARE MANY OF THEM WILL, THEY ARE SUBJECT TO THE SABV POLICY AND THEY ARE SUBJECT TO THE POLICIES ON ENHANCING RIGOR AND REPRODUCIBILITY THROUGH RIGOR AND TRANSPARENCY, A KEY POINT FOR RIGOROUS EXPERIMENTAL DESIGN AND ADHERENCE TO SCIENTIFIC METHOD. IN THAT POLICY, NIH SPECIFICALLY SAYS WE EXPECT DESIGNS THAT ARE APPROPRIATE, UNBIASED DESIGNS BASICALLY, THAT MAXIMIZE THE OUTCOME, RIGOROUS OUTCOME. SO I THINK THAT THROUGH THE WORK OF THOSE INSTITUTES AND CENTERS AND HOPEFULLY THROUGH THE CCRWH RECONSTITUTION, AND THROUGH EFFORTS THAT ARE ORGANIZED BY THOSE INSTITUTES AND CENTERS, WE ARE TRYING TO ENSURE THAT THOSE ISSUES ARE ADDRESSED. I ASSURE YOU THAT OUR VOICE, WE ARE ALWAYS ADVOCATING FOR THAT. BUT I -- YOU KNOW, OTHER THAN THAT -- YOU KNOW, THEY ARE ALL SUBJECT TO THE POLICY. WE'RE ADVOCATING FOR THEM. IT'S IMPORTANT THAT THE NEW STRATEGIC PLANS AS YOU HEARD FROM INSTITUTES AND CENTERS FROM MISS WATSON ARE GOING TO BE ARTICULATORRING HOW EACH INSTITUTE IS ADDRESSING A STRATEGIC PLAN OBJECTIVE THAT'S RELEVANT TO THAT MISSION. AND SO GOING FORWARD, I HOPE THAT WE'LL BE ABLE TO COME BACK TO YOU AND GIVE YOU SPECIFIC EXAMPLES OF HOW INSTITUTES AND CENTERS AND NIH OFFICES HAVE ADDRESSED THE HEALTH OF WOMEN THROUGH THEIR ACTIVITIES. >> I WAS AT THE PRECISION MEDICINE WORKSHOP, SEEMED TO BE MORE REPRESENTATIONAL. MAYBE I'M MAKE A RECOMMENDATION WHEN WE VOTE EACH INITIATIVES COMES, PRECISION MEDICINE HAS BEEN HERE, MY CONCERN IS THE TRAIN STARTS MOVING AND IT'S TOO LATE, THINGS BECOME AN ADD-ON AS OPPOSED TO INTENTIONAL FOCUS TO THINK ABOUT HEALTH AND WELL-BEING OF WOMEN AND NOT JUST REPRODUCE. I ACTUALLY LIKE TO MAKE A RECOMMENDATION THAT EACH ONE OF THOSE PEOPLE WHO ARE IN CHARGE OF THOSE INITIATIVES WOULD COME AND MAKE A PRESENTATION IN FRONT OF THIS GROUP TO SPECIFICALLY ADDRESS THESE ISABEL. >> THANK YOU, DR. GREEN. DO YOU WANT TO MAKE THAT OFFICIAL MOTION? OKAY. >> I'VE GOT A SECOND. >> DR. GREEN HAS MOVED LEADERS OF THE MAJOR INITIATIVES THAT WERE PRESENTED IN THE DIRECTOR'S REPORT BE INVITED TO PRESENT AT A FUTURE ADVISORY COMMITTEE MEETING. DR. BECKER HAS SECONDED THAT. I DON'T KNOW THAT WE NEED A VOTE BUT WE'LL GO AHEAD AND DO A VOTE JUST IN CASE. IS EVERYONE IN FAVOR? WHO IS IN FAVOR OF THAT? IF YOU ARE, PLEASE INDICATE BY SAYING AYE. >> AYE. >> ANYONE OPPOSED TO THAT APPROACH? ANYBODY ABSTAINING? THANK YOU. LAST QUESTION. WE CAN GIVE DR. BEVANS A LITTLE EXTRA TIME THIS WAY. >> THE TWO ISSUES THAT ARE CRITICALLY IMPORTANT THAT YOU LED WITH, THE OPIOID CRISIS AND THE RISING MATERNAL MORTALITY, ARE GOING TO BE ADDRESSED I'M SURE WITH SEX AS A BIOLOGICAL VARIABLE, BUT IT'S PROBABLY EQUALLY IMPORTANT TO MAKE SURE THAT ISSUES OF GENDER ARE BEING ADDRESSED, AND HOW CAN WE HELP ENSURE THAT HAPPENS, BECAUSE IT'S PROBABLY NOT ALL ABOUT BIOLOGY. >> SO NOEL, BY ISSUE OFFER, DO GENDER, ALL THE ISSUES THAT AFFECT THE HEALTH OF A WOMAN, EVERYTHING, RIGHT? >> YES. >> YOUR QUESTION IS HOW CAN WE ENSURE THAT WE MOVE BEYOND JUST SEX, AND WE CLEARLY WANT TO DO THAT. SO MUCH SO THAT THAT -- REFERENCE TO GENDER, IMPORTANCE OF GENDER, ROLES, DYNAMICS, ALL THE MULTI-DIMENSIONS OF GENDER, WHICH IS A MUCH MORE COMPLEX SOCIAL CONSTRUCT THAN IS SEX, WERE REFERENCED IN THE DOCUMENT THAT WAS MADE AVAILABLE THROUGH THE SABV POLICY. AND I THINK THAT AS WE MOVE FORWARD WITH NEW CLINICAL TRIAL DESIGNS, THERE ARE BIG CHANGES IN THAT SPACE AS YOU KNOW, POTENTIALLY NEW WAYS OF DEFINING WHAT CONSTITUTES WOMEN'S HEALTH AND WOMEN'S HEALTH RESEARCH THAT'S AN OPPORTUNITY AGAIN TO CLARIFY FOR THE SCIENTIFIC COMMUNITY HOW COMPLE HEALTH IS AND HOW CRITICALLY IMPORTANT IT IS TO ACCOUNT FOR BOTH INTERNAL AND EXTERNAL FACTORS, TO ADDRESS COMPLEX PROBLEMS. AND I WOULD SAY FROM OUR PERSPECTIVE ONE OF THE MOST APPROPRIATE WAYS TO BE ABLE TO DRIVE THAT IS THROUGH THE INCORPORATION OF INTERDISCIPLINARY RESEARCH APPROACHES TO PROJECTS. AND THAT ENCOURAGES BIOLOGICAL, BIOMEDICAL, BEHAVIORAL, SOCIAL SCIENCE PERSPECTIVE, AND YOU KNOW THAT'S BEEN A LONG STANDING COMMITMENT OF LONG BEFORE I JOINED ORWH SO I THINK ONE WAY OUR COLLEAGUES CAN ASSIST, WORKING THROUGH THE ACADEMIC COMMUNITY AROUND BETTER INTEGRATING AND OPERATIONALIZING INTERDISCIPLINARY RESEARCH WHICH HAS CHALLENGES, RIGHT? IN TERMS OF TENURE, TEAM SCIENCE, WHAT IS IT, IS IT MULTI, IS IT TRANS, HOW DO WE MEASURE IT, HOW DO WE LOOK AT IMPACT, ARE YOU ALL REALLY WORKING TOGETHER IN A NEW WAY, ARE YOU JUST SITTING AROUND THE TABLE ADMIRING THE PROBLEM IN THE MIDDLE OF THE TABLE. WE'RE DONE WITH THAT, RIGHT? SO I THINK THAT SYSTEMS OF REWARD IN OUR ACADEMIC& ORGANIZATIONS, ATTENTION TO WAYS THAT WE CAN ASSESS AND MEASURE THE IMPACT OF INTERDISCIPLINARY EFFORTS, HIGHLIGHTING INTERDISCIPLINARY EFFORTS, CHAMPIONING THEM, SHOWING THE VALUE WOULD BE ONE REALLY TANGIBLE AND PRACTICAL WAY TO INCORPORATE GENDER AS WE MOVE FORWARD. WE ALWAYS LOOK FORWARD TO SPECIFIC SUGGESTIONS FROM THIS ADVISORY COMMITTEE ON WAYS TO DO THAT. THE OTHER WAY IS WE ALL HAVE TO BE ON THE SAME PAGE FIRST ABOUT THESE TERMS. SO IF IN EVERY PRESENTATION YOU DO, YOU INCLUDE A DEFINITION OF SEX AND DEFINITION OF GENDER, YOU'RE GOING TO HAVE, YOU KNOW, MONUMENTAL IMPACT IN JUST GETTING US ON THE SAME PAGE IN TERMS OF WHAT ARE WE TALKING ABOUT. WE MAY OR MAY NOT AGREE WHAT WE SHOULD BE DOING ABOUT IT BUT SHOULD ALL BE UNDERSTANDING WHAT WE'RE TALKING ABOUT. >> WITHOUT FURTHER ADO I WANT TO BRING UP DR. MARGARET BEVANS, ASSOCIATE DIRECTOR FOR CLINICAL RESEARCH AT ORWH, TO GIVE US AN UPDATE ON THE DEVELOPMENT OF THE TRANS-NIH STRATEGIC PLAN FOR WOMEN'S HEALTH RESEARCH. DR. BEVANS. >> THANK YOU VERY MUCH, DR. CLAYTON. THANK ALL OF YOU FOR BEING HERE TODAY, PRETTY LIVELY, I HAVE TO SAY. EVERYBODY SITTING TALL AND VERY ENGAGED. I HOPE WE CAN CONTINUE AS WE MOVE FORWARD TALKING ABOUT WHERE WE ARE WITH THE STRATEGIC PLAN. BEFORE I BEGIN, I WANT TO ACKNOWLEDGE ALL THE OTHER INDIVIDUALS WHO HAVE BEEN INVOLVED IN THE STRATEGIC PLAN PROCESS STARTED IN 2017. I STAND HERE AS A REPRESENTATIVE OF ALL OF ORWH, MANY INDIVIDUALS IN OUR TEAM HAVE WORKED IN DIFFERENT PHASES AT DIFFERENT LEVELS OF INTENSITY, AND CURRENTLY WE HAVE A CORE TEAM LED BY DR. DENISE FREDERICK, MELISSA HARRINGTON AND PARIS WATSON, STRONG MEMBERS OF OUR CORPS, SPOT TEAM, OUR STRATEGIC PLAN PLANNING ORGANIZATIONAL TEAM AT ORWH, HAVE BEEN GIVING ENDLESS HOURS AS WELL AS MANY MEMBERS OF THE GROUP. THANK YOU TO ALL OF THEM. I HOPE I DO THEM JUSTICE IN REPRESENTING ALL THE WORK. THE OUTLINE FOR TODAY IS THE NEXT 15 OR SO MINUTES I'M GOING TO SPEND A LITTLE TIME PROVIDING THE UPDATE ON THE STRATEGIC PLANNING PROCESS, I'LL GIVE A LITTLE BACKGROUND AND SHARE OUR TIMELINE, AND SHARE OUR, IF YOU WILL, FRAMEWORK THAT IS A VERY IN-PROCESS PRODUCT AND SO WE'RE LOOKING FOR ADDITIONAL FEEDBACK ON THAT TODAY. THAT FRAMEWORK INCLUDES SPECIFIC STRATEGIC PRIORITIES, AS WELL AS SOME FOUNDATIONAL PRINCIPLES. OUR OUTCOMES OF OUR STRATEGIC PLANNING WORKING GROUP, A SUBGROUP OF THE COMMITTEE AT LARGE, HAS BEEN WORKING ON SOME OF THESE ISSUES ALREADY. IT'S GOING TO REPORT OUT ON THAT TODAY, OR PART OF MY PRESENTATION IS TO REPORT OUT ON THAT. AND THEN DR. JUDY REAGANSTEINER IS GOING TO FACILITATE A CONVERSATION WITH ALL OF US AFTER MY PRESENTATION TO ENGAGE YOU IN ADDITIONAL WAYS OF THINKING. I WANT TO START BY TAKING A MINUTE TO SHOW WHERE THE STRATEGIC PLAN FITS INTO THE WORK WE'RE DOING. DR. CLAYTON MENTIONED OUR VISION ON THE RIGHT-HAND SIDE OF THE SLIDE. I WON'T REPEAT THAT. ON THE LEFT-HAND SIDE IS THE MISSION OF THE NIH AS IT RELATES TO WOMEN'S HEALTH, REFLECTING THE MANDATE GIVEN IN 1993. THE STRATEGIC PLAN FITS BETWEEN THE TWO. AND IS REALLY A ROAD MAP, IF YOU WILL, OUTLINING THE STEPS THAT WE NEED TO TAKE BETWEEN THE MISSION, THE WORK THAT WE'RE DOING, AND THE VISION, WHERE WE WANT TO BE. IN ADDITION TO THAT, BEFORE I GO ON I WANT TO HIGHLIGHT THAT THIS STRATEGIC PLAN THAT'S THE CIRCLE IN THE MIDDLE OF THIS DIAGRAM REALLY REFLECTS THE TRANS-NIH STRATEGIC PLAN, I WANT TO CALL OUT THAT DIFFERENCE. THE STRATEGIC PLAN THAT WE'RE TALKING ABOUT TODAY IS A TRANS-NIH STRATEGIC PLAN. THIS IS NOT A PLAN FOR ORWH ALONE. THIS IS A PLAN THAT IS GOING TO BE ENACTED ACROSS ALL OF THE 27 INSTITUTES AND CENTERS OF THE NIH. IN ADDITION TO THAT, WE HAVE INDIVIDUAL STRATEGIC PLANS, AS YOU HEARD MENTIONED BY PARIS WATSON PREVIOUSLY NOW REQUIRED TO INTEGRATE WOMEN'S HEALTH INTO SPECIFIC MISSION AREAS. AS YOU CAN SEE THERE'S A LOT OF ATTENTION RIGHT NOW ON HOW WE ARE ADDRESSING THE HEALTH OF WOMEN, AND THIS STRATEGIC PLAN IS JUST ONE, ONE MAJOR PIECE OF THAT, IF YOU WILL. SO JUST TO TAKE A MINUTE TO REFLECT ON THE TIMELINE, WHERE WE'VE BEEN AND WHERE WE'RE GOING, BACK IN SEPTEMBER OF 2017 WE PRESENTED TO THIS COMMITTEE AS WELL ON THE REQUEST FOR INFORMATION WHICH WAS ABOUT TO BE LAUNCHED. THAT REQUEST FOR INFORMATION WAS INDEED LAUNCHED, AND ALL OF THAT FEEDBACK CAME BACK TO US AND WAS ANALYZED AND REFINED INTO A FRAMEWORK THAT I'M GOING TO SHARE WITH YOU TODAY. THAT FRAMEWORK HAS ALSO BEEN PRESENTED TO THE STAFF OF ORWH, TO THE DIRECTOR OF NIH AND HIS TEAM AS WELL AS THE NIH COUNCIL OF COUNCILS. AND THE PROCESS THAT WE'RE TAKING TO ENGAGE ALL THE INSTITUTES AND CENTERS AND MANY OFFICES HERE AT THE NIH WAS APPROVED. IN ADDITION TO THAT WE WORK WITH OUR COORDINATING COMMITTEE FOR RESEARCH ON WOMEN'S HEALTH AS WELL AS YOU, AS THE ADVISORY COMMITTEE, AND MANY OF YOU IN MORE DETAIL AS PART OF OUR SPECIFIC WORKING GROUP. I'LL GO OVER THE NEXT STEPS TOWARDS THE END OF THE TALK. SO I WANT TO SPEND A MINUTE TALKING ABOUT THE REQUEST FOR INFORMATION. IT WAS OUT BETWEEN SEPTEMBER 12 AND NOVEMBER 10. AND WE RECEIVED 145 RESPONSES. WHICH WAS AN AMAZING NUMBER OF RESPONSES. ACTUALLY REFLECTED SORT OF A -- IT WAS A NEW BENCHMARK IN THE OFFICE OF THE DIRECTOR. AS YOU CAN SEE, WE GOT EXTENSIVE STAKEHOLDER ENGAGEMENT. ALTHOUGH RESEARCHERS WERE THE LARGEST PERCENTAGE OF INDIVIDUALS WHO RESPONDED, YOU CAN SEE WE HAD REPRESENTATION FROM ADVOCACY GROUPS, CLINICIANS, AND PATIENTS. AND ORWH IS PLEASED TO ACKNOWLEDGE AND THANK EVERYONE FOR THESE CONTRIBUTIONS. MANY OF WHOM MAY BE IN THE ROOM HERE TODAY AS WELL AS JOINING US VIA THE VIDEOCAST. THESE RESPONSES REALLY REPRESENT THE DIVERSITY OF ORGANIZATIONS AND INDIVIDUALS WHO ARE COMMITTED TO THE WORK EVERY DAY TO ADVANCE WOMEN'S HEALTH RESEARCH. SO, NEEDLESS TO SAY, 145 NARRATIVE RESPONSES WAS A LOT OF INFORMATION TO GO THROUGH. AND SO WE NARROWED THAT DOWN IN OUR FIRST PHASE TO 45 BROAD CATEGORIES, AND THEY ARE REPRESENTED ACROSS MANY SPANS. BUT I'M GOING TO HIGHLIGHT A FEW OF THE AREAS THAT THEY REPRESENTED. CLEARLY WE ARE A RESEARCH INSTITUTION. WE GOT A LOT OF FEEDBACK ON SPECIFIC RESEARCH TOPICS THAT WE SHOULD BE CONSIDERING. THERE WAS INFORMATION IN THE RFI THAT ADDRESSED WHAT WE CALLED CROSS-CUTTING THEMES, THEMES THAT DIDN'T GO TO ANY SPECIFIC RESEARCH TOPIC BUT ACROSS MANY ASPECTS OF THOSE TOPICS. THERE WAS A LOT OF RESPONSE ABOUT WOMEN IN BIOMEDICAL CAREERS. THERE WAS A LOT OF RESPONSE ABOUT INCLUSION OR OTHER POLICIES THAT AFFECT WOMEN'S HEALTH. THERE WAS A LOT OF DISCUSSION IN THOSE RESPONSES AROUND DISSEMINATION. HOW ARE WE REPRESENTING THE RESEARCH THAT WE'RE DOING AS WE ARE PUSHING IT OUT SO THAT IT CAN BE APPLIED IN PRACTICE OR BE A BUILDING BLOCK FOR OTHER RESEARCH TO FOLLOW. THERE WAS REQUEST AND DIALOGUE ABOUT RESOURCES THAT WE SHOULD BE CONSIDERING, AND THEN OF COURSE THERE WERE RESPONSES THAT WERE SOMEWHAT DIRECTIVE, OR HELPING US UNDERSTAND PROCESSES THAT WE MIGHT NEED TO CONSIDER AS WE MOVE FORWARD, ADVANCING THE SCIENCE FOR HEALTH OF WOMEN. SO WHEN YOU THINK ABOUT THOSE TOPICS, AGAIN WE THEN BROKE THOSE DOWN AND THERE'S A LIST OF MANY, AND BASICALLY THEY COVER THE GAMUT OF ALL ASPECTS OF HEALTH AND DISEASE. BUT WE ENDED UP PUTTING THEM SORT OF IN THREE BUCKETS, IF YOU WILL. THERE WERE DISEASES AND CONDITIONS THAT WERE CALLED OUT. AND THESE ARE JUST A FEW EXAMPLES. THERE WERE TOPICS THAT REALLY GO INTO THAT DISCOVERY SPACE, THINK ABOUT BASIC SCIENCE AND A LOT OF THOSE WERE MICROBIOME AND EPIGENETICS ORIENTED. WE HAD SUGGESTIONS THAT WERE MORE IN THE PUBLIC HEALTH SPACE, LIKE ENVIRONMENTAL INFLUENCES, AND HEALTH BEHAVIORS. WHEN WE TALKED ABOUT THOSE CROSS-CUTTING THEMES, WE ENDED UP PUTTING THOSE IN THREE CATEGORIES. AND WE'RE GOING TO TALK A LOT ABOUT THESE. THIS IS THE SPACE WHERE OUR WORKING GROUP HAS REALLY BEEN HELPING US TO FLESH THIS OUT A LITTLE BIT. THOSE INCLUDE INTERDISCIPLINARY APPROACHES, WAYS TO THINK ABOUT THINGS TO INTENTIONALLY INTEGRATE, AND MULTI-DIMENSIONAL CONSIDERATIONS, WHICH WAS REALLY -- SPEAKS TO THE CONVERSATION WE HAD RIGHT BEFORE I CAME TO THE PODIUM. SO ALL OF THESE RESPONSES ARE CAPTURED TO SOME EXTENT IN THIS FIGURE THAT YOU SEE HERE. THIS FIGURE REPRESENTS CURRENT FRAMEWORK TO ADDRESS THE INTERSECTION OF THE NIH'S MANDATE TO ADDRESS THE HEALTH OF WOMEN, AND ALL OF THOSE COMMENTS, ALL OF THAT INFORMATION THAT WE GOT FROM BOTH INTERNAL AND EXTERNAL STAKEHOLDERS. THE WAY THAT WE'RE MOVING FORWARD RIGHT NOW IS THAT WE ARE CONSIDERING TWO PATHS, IF YOU WILL, THAT ARE STAYING CONNECTED AT MANY JUNCTURES. FIRST, WE'VE CREATED A STRATEGIC PLAN, ALIGNED WITH FIVE PRIORITY AREAS ON THE FRAMEWORK. THESE TEAMS ARE TO CONTRIBUTE TO THE DEVELOPMENT, IMPLEMENTATION AND DISSEMINATION OF THE STRATEGIC PLAN. IT DOESN'T END WITH GETTING A DOCUMENT TOGETHER THAT SAYS THIS IS WHAT WE SHOULD BE DOING AND HOW TO DO IT. WE NEED TO IMPLEMENT THE STRATEGIC PLAN, EVALUATE THE STRATEGIC PLAN, AND MAKE SURE WE ARE DISSEMINATING ALL OF THOSE PIECES. SO THESE TEAMS WE KICK THEM OFF BY HAVING TWO SPECIFIC TRANS-NIH THINK TANK SESSIONS, AND MANY OF THOSE MEMBERS ARE INDIVIDUALS WHO PARTICIPATED ARE HERE TODAY OR ON THE CALL. WE HAD APPROXIMATELY 70 MEMBERS FROM ACROSS THE NIH JOIN THESE THINK TANKS, AND THEY REPRESENTED ALL 27 INSTITUTES AND CENTERS, AS WELL AS MANY OF THE OFFICES. EACH OF THESE TEAMS IS CO-CHAIRED BY A MEMBER OF THE ORWH STAFF, AS WELL AS AT LEAST ONE MEMBER OF ONE OF THE SPECIFIC INSTITUTES OR CENTERS. THE GOALS OF EACH OF THESE TEAMS IS SPELLED OUT HERE. FOR THE RESEARCH STRATEGIC PRIORITY OUR GOAL IS TO IDENTIFY AND ADVANCE INNOVATIVE AND EMERGING AREAS OF WOMEN'S HEALTH œFOR THE METHODS TEAM, THEIR GOAL IS TO COME UP WITH OBJECTIVES THAT WILL HELP US DEVELOP AND ENHANCE RESEARCH METHODS AND RESOURCES. FOR THE DISSEMINATION TEAM, THEIR GOAL IS TO COME UP WITH OBJECTIVES TO DISSEMINATE RESEARCH ON WOMEN'S HEALTH. FOR THE CAREERS TEAM THEY ARE LOOKING TO DEVELOP OBJECTIVES FOR PROMOTING THE RECRUITMENT, RETENTION, REENTRY AND ADVANCEMENT OF WOMEN, AND TO IMPROVE NIH INVESTMENT IN WOMEN'S HEALTH RESEARCH. I WANT TO GO BACK ONE SLIDE FOR JUST A SECOND AND HIGHLIGHT THE FACT THAT THOSE CROSS-CUTTING THEMES THAT I MENTIONED EARLIER, YOU SEE THOSE AT THE TOP OF THE FIGURE. THEY ARE NOW CALLED FOUNDATIONAL PRINCIPLES, AS WE HAVE GONE THROUGH AN ITERATIVE PROCESS IN TRYING TO SORT OF UNDERSTAND THEM AND FLESH THEM OUT A BIT MORE. THEY DON'T NECESSARILY CROSS-CUT EVERY ASPECT OF THE PLAN, BUT THEY ARE INDEED FOUNDATIONAL PRINCIPLES THAT WE NEED TO BUILD ON TO ENSURE WE'RE ADVANCING SCIENCE FOR THE HEALTH OF WOMEN. AND THEN AT THE BOTTOM OF THE DIAGRAM YOU'LL SEE IMPLEMENTATION PLAN, I REFERRED TO THAT A MINUTE AGO, THAT WILL INCLUDE THE WAY WE IMPLEMENT THE PLAN BOTH ACROSS THE 27 ICs AND CENTERS AS WELL AS MANY ACTIONS WILL BE INVOLVED IN. THE ICs WORKING CURRENTLY WITH OUR OFFICE TO DEVELOP THESE OBJECTIVES. THE SECOND PATH WE STARTED BY WORKING WITH A SUBGROUP OF THE ACRWH TO FLESH OUT FOUNDATIONAL PRINCIPLES AND SPEAKING TO WOMEN'S HEALTH AND HEALTH OF WOMEN. TO ADDRESS THIS FIRST OBJECTIVE OF HEALTH OF WOMEN WE ARE LOOKING AT DEFINING THE RECOMMENDATION -- LOOKING AT THE -- ONE SECOND PLEASE. THE RECOMMENDATION WAS THAT THE HEALTH OF WOMEN IS A MORE COMPREHENSIVE AND ACCURATE TERM AS COMPARED TO WOMEN'S HEALTH. THE HEALTH OF WOMEN REALLY ENCOMPASSES ALL ASPECTS OF HEALTH AND DISEASE, ACCOUNTING FOR THE INFLUENCE OF SEX AND GENDER, WHICH INCLUDES CONDITIONS THAT AFFECT ONLY WOMEN, SUCH AS REPRODUCTIVE HEALTH, AS WELL AS ASPECTS OF HEALTH AND DISEASE THAT MAY AFFECT WOMEN DIFFERENTLY FROM MEN. THIS NEXT SLIDE REPRESENTS THE FIRST OF THE FOUNDATIONAL PRINCIPLES WHICH WE TITLED THE MULTI-DIMENSIONAL CONSIDERATIONS. THE INTENT OF THIS PRINCIPLE IS TO RECOGNIZE THAT THE HEALTH OF WOMEN IS AFFECTED BY MANY FACTORS. HERE IS A FIGURE THAT ILLUSTRATES A WOMAN'S LIFE TRAJECTORY. ALTHOUGH EVERY STAGE OF LIFE HAS ITS UNIQUE TRAITS, IT IS CRUCIAL TO EXAMINE HEALTH AS A CONTINUUM, BECAUSE HEALTH ADVANTAGE AND DISADVANTAGES ARE CUMULATIVE ACROSS THE LIFESPAN. WE WANT TO HIGHLIGHT THE INTERNAL FACTORS, AND THIS IS WHERE SEX COMES IN. SEX INFLUENCES AT THE MOLECULAR, CELLULAR AND ORGAN LEVELS, CAN HAVE A SIGNIFICANT ROLE. AND WE'RE LABELING THIS CURRENTLY THE BIOLOGICAL PERSPECTIVE. WE THINK OF THE MANY, MANY EXTERNAL FACTORS, SUCH AS DEMOGRAPHICS, SES, LIFESTYLE, OTHERS THAT WE HAVE REFERENCED HERE ON THE SLIDE. THESE REPRESENT REALLY THE CONTEXT IN WHICH WE LIVE. AND OF COURSE WE ALL RECOGNIZE THERE IS A CONNECTION, AND INTERACTION, BETWEEN THE INTERNAL AND EXTERNAL FACTORS THAT WE CANNOT IGNORE. SO THE NEXT FOUNDATIONAL PRINCIPLE THAT I WANT TO TALK ABOUT IS ONE THAT WE CURRENTLY HAVE LABELED AS INTENTIONAL INTEGRATION. THIS PRINCIPLE REFERS TO THE THOUGHTFUL CONSIDERATION OF SEX AND GENDER AS WELL AS THE OTHER -- MANY OTHER FACTORS THAT I JUST PRESENTED, IN ALL PHASES OF A STUDY, RECOGNIZING AS WELL THE CONTINUUMS OF HEALTH AND DISEASE, RESEARCH, AND HEALTH CARE. MORE SPECIFICALLY, THIS INCLUDES THE INTENTIONAL INTEGRATION IN RESEARCH ADDRESSING EVERYTHING FROM HEALTH PROMOTION TO DISEASE PREVENTION, AND OF COURSE THE MANAGEMENT OF SPECIFIC CONDITIONS AND DISEASES. IT ALSO CONSIDERS THE FULL RANGE OF TYPES OF RESEARCH, BEGINNING AT THE BENCH, AT THE BASIC SCIENCE LEVEL. RECOGNIZING THROUGH TRANSLATION, TRANSLATIONAL RESEARCH INTO THE CLINICAL RESEARCH SPACE, AND THE CLINICAL RESEARCH SPACE THAT EVIDENCE THEN REALLY BEING TESTED IN THE IMPLEMENTATION SCIENCE SPACE AS WE MOVE THIS EVIDENCE INTO PRACTICE. THERE ARE TWO WAYS TO THINK ABOUT WHERE WE GO NEXT. SOME OF THAT WORK MAY SUGGEST THERE ARE ADDITIONAL GAPS THAT GO BACK TO THE BENCH FOR EXPLORATION. AND SOME OF THAT WORK MAY BE PUSHED OUT, IF YOU WILL, INTO THE POLICY SPACE, EDUCATION SPACE, AND REALLY THROUGHOUT THE SYSTEMS OF CARE. THE LAST PRINCIPLE THAT I JUST WANTED TO HIGHLIGHT RELATES TO INTERDISCIPLINARY RESEARCH. DR. CLAYTON WAS JUST DOING A BEAUTIFUL JOB SPEAKING TO THIS ISSUE. WE'RE REALLY LOOKING HERE TO LOOK AT PARTNERSHIPS THAT COLLABORATE ACROSS DISCIPLINARY BOUNDARIES, AND THERE ARE MANY TERMS UNDER THE LARGER UMBRELLA OF TEAM SCIENCE THAT SPEAK TO THAT. CURRENTLY, WE ARE WORKING WITH THE DEFINITION THAT YOU SEE HERE ON THE SLIDE, FOR INTERDISCIPLINARY RESEARCH THAT CAME FROM THE NATIONAL ACADEMIES IN 2008. THIS IS REALLY REFERRING TO A MODE OF RESEARCH THAT INTEGRATES INFORMATION, DATA, TECHNIQUES FROM TWO OR MORE BODIES OF SPECIALIZED KNOWLEDGE TO ADVANCE FUNDAMENTAL UNDERSTANDING, SOLVE PROBLEMS, WHOSE SOLUTIONS ARE BEYOND THE SCOPE OF A SINGLE DISCIPLINE, OR AREA OF RESEARCH PRACTICE. SO ALTHOUGH WE'RE FOCUSING ON A TRANS-NIH STRATEGIC PLAN, I REALLY WANT TO HIGHLIGHT THE UNIQUE ROLE OF ORWH IN THIS WORK. ORWH CREATES OPPORTUNITIES FOR SYNERGY BETWEEN THE INSTITUTES, CENTERS AND OFFICES. WE HELP IDENTIFY GAPS IN EVIDENCE, PRACTICE AND HEALTH, CONVENE INTERDISCIPLINARY EXPERTS WITH COMMON INTERESTS, AND LEVERAGE OUR CO-FUNDING RESOURCES WITH OUR ICO PARTNERS WHICH YOU HEARD HIGHLIGHTED IN THE DIRECTOR'S REPORT. WE ADVISE ON THE INCLUSION OF WOMEN, MINORITIES AND INDIVIDUALS ACROSS THE LIFE COURSE IN CLINICAL RESEARCH. WE PROMOTE THE ADVANCEMENT OF WOMEN IN BIOMEDICAL CAREERS. PROVIDE A PLATFORM FOR INTENTIONAL INTEGRATION OF SEX AND GENDER, AND REALLY ADVANCE A MULTI-DISCIPLINARY VIEW OF THE HEALTH OF WOMEN. SO OUR NEXT STEPS, WHICH ARE VERY AMBITIOUS, INCLUDE TAKING& THE OBJECTIVES THESE FIVE TEAMS ARE DEVELOPING, AND CONTINUE TO REFINE THEM, DEVELOP SOME WAYS TO SPEAK TO THEM AND CREATE THE NEXT DRAFT OF THE STRATEGIC PLAN FOR ORWH'S REVIEW. WE WILL THEN SHARE THAT FINAL PLAN, OR FINAL DRAFT PLAN, WITH ALL OF YOU, AS WELL AS THE LEADERSHIP HERE AT THE NIH FOR FINAL APPROVAL. WE HOPE TO GO INTO PRODUCTION OF THE STRATEGIC PLAN, THE END OF THE FISCAL YEAR, AS WELL AS PLAN TO DISSEMINATE IT BY OCTOBER OF 2018. I WANT TO CALL OUT ALL OF OUR -- MAKE A SPECIAL THANKS TO ALL OF OUR WORKING GROUP MEMBERS WHO HAVE GIVEN US MUCH OF THEIR TIME, ESPECIALLY IN THE PAST COUPLE WEEKS, INCLUDING LAST NIGHT, TO BEGIN TO REALLY WORK THROUGH THIS AND DEVELOP A COMMON WAY TO JUST HAVE DIALOGUE ABOUT IMPROVING THE HEALTH OF WOMEN. AT THIS TIME I TURN THE PODIUM OVER TO DR. JUDY REAGANSTEINER TO LEAD OUR DISCUSSION. THANK YOU. [APPLAUSE] >> THAT'S SO AMAZING, SO BROAD, SO IMPRESSIVE AND COMPREHENSIVE THAT I'M THRILLED TO BE PART OF IT. IT'S BIG. I REMEMBER WHEN I WAS A YOUNG ASSISTANT PROFESSOR, I DID A REVERSE SITE VISIT AS A UNIVERSITY I WILL NOT NAME WITH A PROFESSOR I WILL NOT NAME, A HUGE CARDIOVASCULAR TRIAL TO BE DONE IN 400 PEOPLE, IMPORTANT CARDIOVASCULAR PREVENTION, THE PEOPLE STUDIED WERE ALL MEN. I SAID WHY AREN'T YOU INCLUDING WOMEN? HIS ANSWER WAS VERY SIMPLE AND QUICK. BECAUSE THEY ARE SO COMPLICATED. HE SAID THAT OUT LOUD. AND I DIDN'T SCORE HIM PARTICULARLY HIGHLY, AS YOU CAN IMAGINE, TO BE NICE. BUT NOW I DON'T THINK ANYONE WOULD DREAM OF HOPEFULLY SAYING SUCH A THING. WE HAVE COME A LONG WAY BUT WE HAVE A LONG WAY TO GO. THIS PLAN REALLY ADDRESSES A LOT OF THAT. SO I'M HERE TO ASK FOR DISCUSSION ABOUT THE ENTIRE PLAN, AND ONE OF THE THINGS I FIRST NOTICED WHEN WE TALKED ABOUT IT IS SWITCH TO TALKING ABOUT THE HEALTH OF WOMEN RATHER THAN WOMEN'S HEALTH, AND ACTUALLY EVOKED A LOT OF DISCUSSION. THAT'S ONE POINT. AND THEN THE SEX AND GENDER VERSUS WOMEN'S HEALTH, I MEAN, WOMEN'S HEALTH TALKING ABOUT PREGNANY YOU'RE TALKING ABOUT WOMEN'S HEALTH, NOT WHEN YOU'RE TALKING ABOUT THE BABY'S, BUT THE WOMAN. AND PREGNANCY PER SE. ALMOST ANYTHING ELSE IN THE LIFESPAN CAN BE SEX DIFFERENCES. I THINK THIS PLAN ENCOMPASSES A LOT OF THAT. I WANT TO HEAR FROM EVERYBODY WHAT THEY THINK AND NOW IS THE TIME AS WE CONTINUE TO WORK ON THE PLAN, A HUGE, HUGE PROJECT, SO YOUR INPUT IS CRITICAL TO US GOING FORWARD THE BEST POSSIBLE WAY. WHO WANTS TO LEAD OFF? >> MARGARET AND JUDY, CAN YOU GO BACK A COUPLE SLIDES, TO THE ONE, THERE WAS A LOT OF DISCUSSION ABOUT IT. >> TELL ME WHEN. >> THAT ONE RIGHT THERE. SO THAT ONE AND -- SO A COUPLE THINGS. MUCH IMPROVED, YOU'VE GOT SOME WORK TO DO, BUT MUCH IMPROVED, I REALLY THINK THE WORD "HEALTH POLICY" IS SORT OF LIMITING BECAUSE WE'RE TALKING ABOUT ECONOMIC AND SOCIAL POLICY. I DON'T KNOW IF YOU LEAVE IT AS THE WORD "POLICY." AND THEN YOU HAVE TO THINK ABOUT SMALL P VERSUS BIG P POLICY. SO I'LL JUST PUT THAT OUT THERE. GO BACK ANOTHER SLIDE OR TO TWO. RIGHT THERE. SO WHEN YOU HAVE THIS CONVERSATION ABOUT EXTERNAL FACTORS, WE PUT UP SPECIAL DETERMINANTS OF HEALTH, AND I THINK AGAIN WE NEED TO -- I'M SURPRISED I MISSED THIS. ECONOMIC, BEHAVIORAL, YOU KNOW, DETERMINANTS OF HEALTH. AND SO THAT NEEDS TO BE -- I THINK IT NEEDS TO SPECIFICALLY BE SPELLED OUT BECAUSE FROM THAT PERSPECTIVE, IT DOESN'T SPECIFICALLY SAY WE'RE LOOKING AT THE BROAD WOMEN, I MEAN, IN REGARDS TO LGBTQ, IT DOESN'T SPEAK TO, FROM MY PERSPECTIVE, RACIAL AND ETHNIC MINORITIES, IT'S SORT OF IMPLIED BUT THIS WILL BE THE LARGEST MAJORITY, BECOMING A MAJORITY, MINORITY COUNTRY. AND WE KNOW BEHAVIOR CERTAINLY INFLUENCES. I WOULD ACTUALLY SPELL OUT THAT, INSTEAD OF SOCIAL DETERMINANTS, BRING THAT OUT. STACY? >> THANK YOU. EXCELLENT WORK. YOU CLEARLY WORKED A LOT LAST NIGHT AFTER WE SENT YOU HOME. A COUPLE RECOMMENDATIONS, I'M SURE YOU DIDN'T HAVE TIME FOR THIS LAST NIGHT. EVERY TIME IT SAYS WOMEN'S HEALTH, I WOULD PUT IN THE HEALTH OF WOMEN, RIGHT? I THINK THAT'S IMPORTANT. I THINK THE COMMENT ABOUT WOMEN ARE COMPLICATED, PEOPLE AREN'T SAYING IT OUT LOUD ANYMORE BUT THEY ARE STILL THINKING IT, RIGHT? AND SO LET'S NOT THINK FOR A MOMENT -- I MEAN THIS GROUP KNOWS THIS, THAT IT'S STILL NOT A THOUGHT THAT A LOT OF PEOPLE HAVE. BOTH MEN AND WOMEN. THIS IS NOT JUST ABOUT MEN. THE OTHER THING ON THIS SLIDE, AND I THINK, YOU KNOW, SINCE I LIVE IN THE WORLD OF REPRODUCTIVE HEALTH AND MATERNITY MORTALITY AND MORBIDITY, I HELPED WITH THE STORY ABOUT THE SCIENTIST FROM CDC, I DON'T KNOW HOW IN AMERICA I HOPE THIS IS OKAY TO SAY, WE DON'T TALK ABOUT RACISM AS AN EXTERNAL FACTOR. THAT AFFECTS THE HEALTH OF WOMEN. AND MEN OF COURSE, BUT WE'RE HERE TODAY TO TALK ABOUT THE HEALTH OF WOMEN. AND MATERNAL MORTALITY IS AN EXCELLENT EXAMPLE OF WHERE YOU CONTROL FOR EDUCATION, ECONOMIC WELL-BEING, ALL OF THOSE FACTORS WE TALK ABOUT AND STILL AFRICAN-AMERICAN WOMEN IN THIS COUNTRY HAVE A HIGHER RATE OF MATERNAL MORTALITY AND MORBIDITY, AND INFANT MORTALITY. NOW, THERE IS SOMETHING THAT WE'RE NOT CAPTURING THERE BECAUSE WE WORK ON ALL OF THIS ALL THE TIME, THAT WE MUST PAY ATTENTION TO. AND SO I THINK IT'S A BOLD STEP, BUT IF WE DON'T DO IT WHO WILL DO IT? I THINK WE HAVE TO PUT IT UP THERE. THAT'S MY RECOMMENDATION. >> SO, I LIKE THE FACT THAT IN UTERO IS THERE. BUT I STILL WANT TO MAKE THE CASE THAT SOME KIND OF SHADING OR SOMETHING THAT REPRESENTS REPRODUCTION CAPACITY GETS REFLECTED. AND I SAY IT AS, YOU KNOW, I KNOW AN OB/GYN, YOU KNOW, THERE WAS A HUGE CONFERENCE TO PUT THE M BACK IN MATERNAL AND CHILD HEALTH. AS A MATERNAL FETAL MEDICINE SPECIALIST WITH MATERNAL MORTALITY THERE WAS A HUGE CONFERENCE TO PUT THE M BACK IN MATERNAL AND FETAL MEDICINE. WHEN YOU'RE PREGNANT YOU PREDICT WHAT'S HAPPENING IN UTERO AND SOME DISEASES PREDICT LATER WHAT'S HAPPENING IN YOUR HEALTH AND, YOU KNOW, A SCREENING TEST FOR THE OTHER CONDITIONS. TO NOT REPRESENT IT I THINK DOESN'T REFLECT THE HEALTH OF WOMEN. >> NOEL? >> I WOULD PUT AT THE BOTTOM, THIS IS A MINOR PUT BUT COULD BE MAJOR, SEX AS A BIOLOGICAL VARIABLE INFLUENCES AT MOLECULAR, CELLULAR, AND WE HAD A CHAT EARLIER IN THE DAY THAT THERE PROBABLY AREN'T ENOUGH BASIC SCIENTISTS AT THIS TABLE AND ON THIS WORKING GROUP BECAUSE THAT ACTUALLY HAS BEEN SORT OF MORE OF A HOLDUP IN TERMS OF THE SABV ROLLOUT. >> YES. >> I THINK THIS IS A GREAT IMPROVEMENT, AND I APPRECIATE THE COMMENTS THAT ARE MADE. I GUESS IT WILL BE YOUR JOB TO BALANCE WHAT YOU CRAM INTO THIS FIGURE VERSUS WHAT GOES INTO THE NARRATIVE, AND I'M CONVINCED YOU CAN'T GET EVERYTHING IN HERE THAT WE ALL MIGHT WANT. THAT SAID, LET ME SUGGEST ADDING ONE MORE THING. [LAUGHTER] I THINK AN INTERESTING ISSUE, DR. CLAYTON TALKED ABOUT OPIOIDS AS JUST ONE OF MANY TREATMENTS, BUT TREATMENTS AS A SPECIFIC TYPE OF EXPOSURE THAT IMPACT BOTH EXTERNAL AND INTERNAL FACTORS, SO I MIGHT CALL THAT OUT BECAUSE THAT CAN HAVE PROFOUND IMPACT ON THE HEALTH OF WOMEN IN BOTH DIRECTIONS. >> CARMEN? >> BRILLIANT. I STILL AM STRUGGLING WITH A COUPLE -- WELL, FIRST OF ALL I WANT TO PIGGYBACK ON MY COLLEAGUE'S COMMENT IT'S ABOUT THE RACISM AND DISCRIMINATION, WHATEVERISM YOU WANT TO CHOOSE, AS RELATED TO RACIAL AND ETHNIC MINORITY PEOPLE, MICRO AND MACRO AGGRESSION, AT WHAT POINT IN TIME DO THEY BECOME INTERNALIZED IN SHORTENED TELOMERE LENGTH, I'M PUTTING THAT OUT THERE. WE WERE TALKING ABOUT WEATHERING, BUT THAT DATA IS THERE. AND SO TO THE EXTENT THAT WE COULD THINK ABOUT THIS IN A LARGER, BROADER CONTEXT, I THINK IS CRITICAL. THE OTHER THING I'M STILL BUGGED BY EARLY, MIDDLE AND LATE. BECAUSE THAT IS VARIABLE. NOW, I THINK I'M STILL EARLY ADULT. YOU UNDERSTAND MY POINT. AND SO I SEE LOTS OF PEOPLE WHO ARE EARLY ADULTS WHO ARE ACCELERATED. I ACTUALLY THINK WE JUST GET RID OF THE EARLY, MIDDLE AND LATE, MAKE IT LESS MESSY. WHATEVER IS -- WHEREVER YOU THINK IT IS. WE HAVE THESE ARBITRARY DEFINITIONS. >> EASY TO THINK ABOUT THAT, THERE ARE SPECIFIC ISSUES SUCH AS ALZHEIMER'S DISEASE WHICH IS FAR MORE PREVALENT IN WOMEN AND VERY MUCH PRIMARILY THE PROBLEM FOR MUCH OLDER PEOPLE. THERE ARE SPECIFIC GERIATRIC ISSUES I WOULD SAY IN WOMEN. >> WELL, YEAH, BUT I THINK ADULTHOOD STILL IMPLIES GERIATRICS ARE INCLUDED IN ADULTHOOD. >> THEY ARE BUT THAT STARTING TO DIFFERENCES IN THE VERY OLD. >> YEAH, BUT THERE ARE ALSO PEOPLE WHO ARE HAVING DEMENTIA AT EARLIER AGES, SO IT'S NOT JUST ALZHEIMER'S, I MEAN THAT'S ONE CAUSE OF DEMENTIA BUT THERE ARE OTHER CAUSES AS WELL. AND SO IF YOU THINK ABOUT WHAT WE WERE TALKING ABOUT EARLIER ABOUT STROKES AND CARDIOVASCULAR DISEASE AND THAT, RACIAL AND ETHNIC MINORITY WOMEN AT INCREASED RISK AND HAVING THAT EARLIER, AGAIN IF WE THINK ABOUT INCORPORATING THIS FOR AN INCREASINGLY NON-WHITE POPULATION, THERE ARE A LOT OF RACIAL AND ETHNIC MINORITIES WHO WOULD LIKE TO GET TO THE ALZHEIMER'S STAGE. >> YES. >> WE WANT TO BE CAREFUL NOT TO DE-EMPHASIZE NEEDS ACROSS THAT SPAN FOR RESEARCH BECAUSE LIKE IN NUTRITION, METABOLISM REALLY CHANGES THROUGHOUT EARLY, MIDDLE AND LATE. AND AT LEAST IN THE NARRATIVE, IF NOT IN THE GRAPHIC, WE NEED TO CALL OUT THAT WE NEED TO UNDERSTAND BETTER. >> WE'RE NOT DISAGREEING ABOUT THAT. >> WE THINK ALSO TO CONSIDER OUR PARTNERS ACROSS ALL THE ICs. THERE'S NIA, FOR INSTANCE. AND WITHOUT LABELING ISSUES AS THOSE OF PRIMARILY OLDER PEOPLE I WORRY SOME OPPORTUNITIES COULD BE -- IT'S A BIGGER DISCUSSION, SO AGREE TO DISAGREE. >> ANY OTHER COMMENTS, YES? >> I'M NOT QUITE SURE HOW TO POSE THIS. I LOVE THE COMMENTS THAT HAVE BEEN MADE BY MY COLLEAGUES AT THIS TABLE. AND REALLY RESPECT THE WORK THAT'S BEEN DONE, BY THE WORKING GROUP. FROM MY OWN PERSPECTIVE, I SEE SOCIAL DETERMINANTS OF HEALTH, AS A RESEARCH SCIENTIST I UNDERSTAND BUT I WANT TO SEE CHOICES IN THERE. I DON'T -- YOU KNOW, I THINK THE EXERCISE OF CHOICE IS SOMETHING THAT WHENEVER WE DEVELOP APPROACHES TO CHANGING BEHAVIOR WE'RE LOOKING AT THE CHOICES THAT WOMEN HAVE. AND TRY TO FIND CHOICE WITHIN THE CONTEXT OF THEIR LIVES. AND I DON'T REALLY SEE THAT IN THIS MODEL, AND I'M STRUGGLING WITH HOW TO MAKE THAT HAPPEN. SO, YOU KNOW, THERE'S SOMETHING ON MY MIND A LOT. I DON'T KNOW -- I CAN BET YOU MY BOTTOM DOLLAR, SO I DON'T HAVE THAT MANY DOLLARS, THAT EVERY SINGLE PERSON IN THIS ROOM FROM EVERY SINGLE CITY, TOWN, VILLAGE, HAS A YOGA STUDIO. RIGHT? WHO DOESN'T HAVE A YOGA STUDIO IN THEIR NEIGHBORHOOD? THEY ARE OPENING UP EVERYWHERE. I MEAN EVERYWHERE. THERE'S A REASON. WHO IS IN THE YOGA STUDIOS? MEN GO TO YOGA STUDIOS TO MEET WOMEN. SO THAT'S WHO IS IN THERE. WOMEN. SO THERE'S PHENOMENON ACROSS THE UNITED STATES OF PROMOTING ONE'S HEALTH IN SUCH WAYS THAT REDUCE STRESS, INCREASE HEALTH. I THINK THAT IT'S A VERY, VERY IMPORTANT PHENOMENON OF CHOICES TO PROMOTE HEALTH. AND I DON'T SEE THAT IN THE MODEL VERY WELL. AND I WISH I COULD JUST COME FORWARD WITH -- I HAVE TO THINK ABOUT HOW TO COME FORWARD WITH THIS SOLUTION TO THAT BUT I WOULD LIKE TO SEE MORE IN THERE ABOUT HEALTH PROMOTION, RATHER THAN JUST DISEASE PREVENTION, BECAUSE WOMEN ARE LIVING LONGER, AND THE CONCEPT OF AGING IS DIFFERENT FOR WOMEN. WE'RE LOOKING AT TROPIC, GREATER COMPLEXITY, WE'RE LOOKING AT GREATER WISDOM, WE'RE LOOKING AT LIVING LONGER, HEALTHIER, AND HOW DOES THAT HAPPEN FOR ALL POPULATIONS OF WOMEN? SO THAT'S AN EMPHASIS I HOPE TO SEE. >> GOOD POINT. WE'VE REACHED THE END OF THE DISCUSSION PERIOD. I'M SURE THE ORWH WANTS TO RECEIVE EVERY COMMENT SO SEND YOUR COMMENTS TO MARGARET, THANK YOU VERY MUCH. >> THANK YOU DR. BEVANS, DR. REGANSTEINER. DR. ARGEWAL? >> GOOD MORNING. I'M DELIGHTED TO INTRODUCE OUR NEXT SPEAKER, DR. SCOTT HAR GREEN, PROFESSOR OF BIOLOGY AND WAS ELECTED TO NATIONAL ACADEMY OF SCIENCE NATIONAL ACADEMY OF MEDICINE, RECEIVED HIS Ph.D. IN MICROBIOLOGY FROM NORTHWESTERN UNIVERSITY, CURRENTLY THE DIRECTOR OF THE CENTER FOR WOMEN'S INFECTIOUS DISEASE AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE, TODAY TALKING ABOUT URINARY INFECTION. >> IT'S CERTAINLY A PLEASURE AND HONOR TO BE HERE. ORWH HAS HAD A MAJOR IMPACT ON MY CAREER AND ON WASHINGTON UNIVERSITY IN GENERAL. IS IT POSSIBLE TO TURN THE LIGHTS DOWN A HAIR? I'M GOING TO HAVE A BUNCH OF PICTURES. I'M GOING TO BE TALKING ABOUT THE RESEARCH DONE BY THESE SIX INDIVIDUALS TODAY AND WHAT WE'VE BEEN TRYING TO DO BY UNDERSTANDING HOST-PATHOGEN INTERACTION IN THE URINARY TRACT TO LAUNCH AN ANTIBIOTIC-SPARING REVOLUTION. MORE AND MORE YOU SEE IN THE HEADLINES IN THE NEWSPAPER ABOUT SUPER-BUGS, THIS IS NOW OCCURRING IN URINARY TRACT INFECTION PATIENTS, PEOPLE CARRYING BACTERIA RESISTANT TO ANTIBIOTICS AS LAST RESORT, HEALTH OFFICIALS SAY IT COULD MEAN THE END OF THE ROAD FOR ANTIBIOTICS. THESE DEPICTIONS HIGHLIGHT URGENT NEED TO DEVELOP A VACCINE OR NEW AND BETTER THERAPEUTIC. THIS IS A MAP SHOWING HOW FLUORO QUINNLIN RESISTANCE IS SPREADING GLOBALLY. 15% OF ALL ANTIBIOTICS PRESCRIBED IN THE UNITED STATES ARE FOR THE TREATMENT OF URINARY TRACT INFECTIONS. AND THIS IS MOSTLY WOMEN. AND SO THIS CONSTITUTES WOMEN'S HEALTH ISSUE, INTERTWINED WITH SPREAD OF ANTIBIOTIC RESISTANCE, ALL GOING INTO THE GASTROINTESTINAL TRACTS OF WOMEN. THIS IS LEADING TO DYSBIOSIS OF THE MICROBIOTA THAT SETS UP FUTURE PROBLEMS, AND I'M TALKING ABOUT THAT. WHEN YOU LOOK AT DRUG RESISTANCE INDEX IT PROVIDES AGGREGATE TREND TO MEASURE EFFECTNESS OF AVAILABLE DRUGS, NUMBER FACING DIFFICULTY INCREASING SINCE 2000s, THIS IS A DISTURBING DEPICTION. AND THIS IS MOSTLY WOMEN. SO WE REALLY NEED TO DO SOMETHING ABOUT THIS. SO, WHAT I'VE TALKED ABOUT HERE IN THE INTRODUCTION IS THE UNMET NEED, OVER 15 MILLION WOMEN SUFFERING PER YEAR IN THE UNITED STATES. INFECTIONS CAN BECOME CHRONIC AND RECURRENT, MORE AND MORE MULTI-DRUG RESISTANT BACTERIA ARE CAUSING THESE INFECTIONS. THIS IS ADDING UP TO INADEQUATE TREATMENT OPTIONS, CATHETER ASSOCIATED UTI ANOTHER BILLION DOLLAR TO HEALTH CARE. THERE'S A REAL NEED TO DEVELOP NEW AND BETTER THERAPEUTICS. TO DEVELOP NEW AND BETTER THERAPEUTICS YOU NEED TO UNDERSTAND THE COMPLEXITY OF THE DISEASE. ONE OF THE REASONS UTI IS SO COMPLEX, MOSTLY BY UROPATH ENGENIC E. COLI, UPEC OCCUPY THE BLOOD, GUT, VAGINA, KIDNEY, EACH WITH A UNIQUE SET OF COLONIZATION REQUIREMENTS THAT I'LL REFER TO AS LOCKS. THE STRAINS ARE DIVERSE, SO THEY SHARE 60% OF THE GENOME SHARED ONE STRAIN CAN DIFFER FROM ANOTHER BY 40%, KEYS ENABLE COLONIZATION, DEPENDING ON HABITAT THEY ARE IN AND PARTICULAR HOST. COLONIZATION AND PERSISTENCE OCCURS WHEN THE LOCK IS OPENED BY THE MATCHING KEY, AND WHAT I'M GOING TO TALK ABOUT TODAY IS SHAPE OF LOCKS CAN CHANGE BASED ON HISTORY, GENETICS AND BEHAVIOR. SO UTI COMPLEXITY RESULTS FROM DIVERSITY AT THE BACTERIAL-HOST INTERFACE. WHEN A STRAIN IS INTRODUCED IF IT'S GOING TO CAUSE DISEASE DEPENDS WHETHER THE URI VIRULENCE PHENOTYPES MATCH WITH DETERMINANTS. SO ULTIMATE RESERVOIR FOR UPEC IS GASTROINTESTINAL TRACT. WHEN THEY GET IN THE BLADDER THEY NEED TO BE ABLE TO STICK, OTHERWISE THEY GET WASHED OUT BY THE FLUIDS AND MATERIALS THAT BATHE SURFACES. SO TO STICK THEY PRODUCE HAIR-LIKE FIBERS KNOWN AS PILLI, USED BY DIVERSE HUMAN PATHOGENS IN A PLETHORA OF DISEASES, I'M TALK ABOUT URINARY TRACT INFECTION TODAY. PILLI MOST IMPORTANT ARE SO CALLED TYPE 1 PILLI, TIPPED WITH FEMH, RECOGNIZING MANNOSE, WITH SPECIFICITY. HUMAN BLADDER IS DECORATED WITH PROTEINS, BINDING TO THE BLADDER, SO THIS BINDING ACTIVATES PLETHORA OF MOLECULAR CROSS-TALK IT THE HOST-PATHOGEN INTERFACE AND ULTIMATELY LEADS TO THIS ZIPPERING OF THESE BLADDER CELLS AROUND THE BACTERIA AT POINTS OF CONTACT BETWEEN THE RECEPTOR AND FIMH ADHESION, ON THEIR WAY TO INVADE, BEGIN TO RAPIDLY REPLICATE AND FILL UP CELLS FORMING INTRACELLULAR BACTERIAL COMMUNITIES, IBCs FOR SHORT. REPLICATION IS SO ROBUST IT CAUSES BLADDER CELLS TO PROTRUDE INT THE LUMEN IN THESE POD-LIKE PROJECTIONS. THIS IS A MECHANISM THE BACTERIA USE TO BUILD UP IN NUMBERS. AND THAT CAN BE APPRECIATED BY THE EXPERIMENTS HERE, WHERE WE INFECTED THE BLADDERS OF MICE WITH GREEN FLUORESCENTLY TAGGED E. COLI, REMOVED THE BLADDER, VIDEOTAPED USING VIDEO FLUORESCENT MICROSCOPY PATHOGENIC CASCADE, NEUTROPHILS ARE BLUE, IBC 10 TO THE 4 BACTERIA, NEUTROPHILS TRYING TO ATTACK IN THE IBC BUT THEY ARE PROTECTED IN THIS BIOFILM LIKE MATRIX. THESE BACTERIA HAVE NOT INVADED AND COALESCED INTO THE IBC BIOMASS AND YOU CAN SEE HERE NOW THE NEUTROPHILS HAVE NO PROBLEM IN GOBBLING UP BACTERIA. SO IBC FORMATION, THESE ARE CLONAL ONE BACTERIUM GETS IN, MULTIPLIES TO 10 TO 4 TO GAIN A FOOTHOLD. THE CYCLE IN THE ACCUSE PHASE OF DISEASE, BUT THERE ARE A NUMBER OF CONSEQUENCES. THE INFECTION CAN RESOLVE WITH OR WITHOUT FORMATION OF THESE RESERVOIRS THAT CAN BE ESTABLISHED IN THE BLADDER EPITHELIUM THAT CAN SERVE AS SEEDS FOR FUTURE RECURRENCES. OR INFECTION CAN GO ON TO BE CHRONIC AND RECURRENT, COUPLED WITH IMMUNOPATHOLOGY AND UNCHECKED IN THE BLADDER. CHECKPOINTS OCCUR EARLY IN THE INFECTION. AND THESE CHECKPOINTS ARE BOTH GENETIC IN NATURE AND ALSO RELATED TO EXPOSURE. SO FOR EXAMPLE HISTORY OF UTIs AMONG THE MOST SIGNIFICANT RISK FACTORS. SO AN INDIVIDUAL WHO HAS HAD AN INFECTION, SHOWN IN GRAY, MUCH MORE LIKELY TO GET A UTI THAN SOMEONE WHO NEVER HAD ONE, SHOWN HERE IN BLACK. THAT'S BEEN KNOWN CLINICALLY FOR DECADES. THE QUESTION IS WHY? WHY IS AN INDIVIDUAL WHO HAD AN INFECTION MORE LIKELY TO GET ONE? MY FORMER GRADUATE STUDENT VALERIE O'BRIEN SAID OUT TO INVESTIGATE, HOW PRIOR HISTORY IMPACTS PATHOGENESIS. SO WHAT SHE DOES IS EITHER TO MOCK INFECT A MOUSE, THESE ARE REFERRED TO AS NAIVE, OR AFFECTS HEN MICE, TWO DIFFERENT FATES ABOUT, ABOUT HALF GO ON TO GET CHRONIC CYSTITIS, DEMARCATED BY UNCHECKED BACTERIAL REPLICATION FOR THE LIFETIME OF THE MOUSE, CFUs PER MILL OF URINE, SENSITIZED MICE. THE OTHER HALF OF THE MICE GO ON TO SPONTANEOUSLY RESOLVE INFECTION, WE REFER TO THESE AS RESOLVED. WHAT SHE DOES IS TREAT MICE WITH ANTIBIOTICS, LET THEM CON HAVE A VALECSE FOR FOUR TO FIVE WEEKS AND CHALLENGE WITH ANOTHER BOLUS OF E. COLI. SENSITIZED MICE ARE SIGNIFICANTLY NOW MORE PREDISPOSED TO RECURRENT INFECTION THAN THE RESOLVED OR NAIVE MORE OR LESS RECALCITRANT. IT TURNS OUT THE BLADDERS ARE BECOMING REMODELED THROUGH THE SENSITIZATION PROCESS. SO WHAT I MEAN? HERE YOU'RE LOOKING AT ELECTRON MICROGRAPHS OF NAIVE SENSITIZED AND RESOLVED BLADDERS. THEY LOOK DIFFERENT BECAUSE THEY ARE. AND THIS IS AFTER ANTIBIOTIC TREATMENT TO CLEAR THE INFECTION, FOUR TO FIVE WEEKS INTO CON HAVE A LESSENS. LUMINAL CELLS ARE SMALLER. WHEN YOU STAY FOR BIOMARKERS OF THE BASAL EPITHELIUM THERE'S EXPANSION OF PROLIFERATIVE ZONE IN SENSITIZED ABSENT IN NAIVE AND RESOLVED. STAIN FOR KERATIN 20, IN WHITE, MORE OR LESS A LACK OF STAINING IN THE SENSITIZED COMPARED TO ROBUST STAINING IN THE NAIVE, SUGGESTING THAT SENSITIZATION HAS RESULTED IN DEFECT IN TERMINAL DIFFERENTIATION. SO I LIKE TO REFER TO THIS PHENOMENON THAT AN INFECTION CAN LEAVE A MOLECULAR IMPRINT ON THE BLADDER SENSITIZING IT TO UTI WHAT DO I MEAN? WHEN WE DO RNA-SEQ ANALYSIS OR PROTEOMIC ANALYSIS ON THESE BLADDERS, WE SEE HUNDREDS OF GENES AND PROTEINS THAT ARE DIFFERENTIALLY EXPRESSED BETWEEN SENSITIZE AND RESOLVED, YOU PUT THESE IN PATHWAYS, SHOWN HERE IN RED, THEIR EFFECT BEING OXIDATIVE STRESS, MORPHOLOGY SENSING IT'S SENSITIVE TO NEUTROPHIL DAMAGE AS CONSEQUENCE OF INFLAMMATION. WHAT DO I MEAN BY THAT? HERE WHEN YOU REEXPOSE THESE BLADDERS TO E. COLI NOW, THERE'S AN OVEREXUBERANT INFLAMMATORY RESPONSE IN SENSITIZED MOUSE RESULTING IN MUCOSAL WOUNDING, SETTING UP PERFECT MILIEU FOR INCHECKED BACTERIAL REPLICATION. SO HERE IS THE DATA. INFECTING SENSITIZED MOUSE RESULTS IN SIGNIFICANTLY MORE CFUs, MORE SEVERE RECURRENT UTI, THAN THE ADULT NAIVE. SENSITIZATION CAUSED BY PRIOR INFECTION LEADS TO LONG LASTING REMODELING THAT INCREASES VULNERABILITY TO SUBSEQUENT INFECTIONS. IN ADDITION SOMETHING ELSE VERY INTERESTING COMES OUT OF THIS. AND THAT IS THE PATHOGENESIS IN MICE WITH HISTORY IS VERY DIFFERENT THAN THE PATHOGENESIS IN NAIVE MOUSE. SO FOR EXAMPLE, MICE WITH A HISTORY OF INFECTION ARE COMPLETELY RECALCITRANT TO IBC FORMATION COMPARED TO NAIVE CONTROLS. THERE'S ALSO SOMETHING INTERESTING THAT WE REFER TO AS COLONIZATION RESISTANCE. SO MICE WITH A HISTORY SENSITIZED AS A RESULT IN THE FIRST 12 HOURS ARE SIGNIFICANTLY -- HAVE SIGNIFICANTLY FEWER CFUs THAN NAIVE CONTROL MICE. THEN SOMETHING REALLY INTERESTING HAPPENS AT 24 HOURS IN THE SENSITIZED GROUP. THAT IS THERE'S A BREAKTHROUGH IN THIS COLONIZATION RESISTANCE. NOW ABOUT HALF THE MICE GO ON TO ACHIEVE THESE HIGH CFUs, SO WHAT'S THE MOLECULAR BASIS OF THIS BREAKING OF COLONIZATION RESISTANCE? IT TURNS OUT IT'S MOST CLOSELY ASSOCIATED WITH INCREASED EXPRESSION OF CYCLOOXIDASE 2, COX2, UPREGULATION IN SENSITIZED COMPARED TO RESHOVELLED, MORE OR LESS LINEAR RELATIONSHIP BETWEEN COX2 EXPRESSION AND BACTERIAL TITERS IN THE URINE AND IN PMNs INFLUXING INTO THE BLADDER. YOU'RE LOOKING AT IN SITU STAINING OF COX2 IN THE BLADDER TISSUE, MICE THAT ARE GOING TO GO ON TO GET CHRONIC RECURRENT INFECTION. SO WHAT'S COX2? IT'S THE ENZYME THAT BREAKS DOWN ERACK DONNIC ACID, INFLAMMATORY MODERATORS, A PERFECT POINT FOR PHARMACOLOGICAL INTERVENTION NSAIDs ARE COX2 INHIBITORS, COULD IMMUNOMODULAR THERAPY ALONE ALTER OUTCOME OF RECURRENT UTI? LOOK AT THE CENTER PANELS. IT'S A LOT OF DATA. TREAT WITH COX2 INHIBITORS, YOU SEE DRAMATIC REDUCTION IN INFLAMMATION, MARKED BY PMN SCORES IN THE BLADDER, ALSO REMARKABLY COX2 INHIBITORS PROTECT THESE MICE FROM RECURRENT UTI. WHAT COX2 SEEMS TO BE DOING IS LICENSING THESE NEUTROPHILS FOR TRANSMIGRATION ACROSS BLADDER EPITHELIUM, RESULTING IN MUCOSAL WOUNDING THAT SETS UP PERFECT MILIEU FOR UNCHECKED BACTERIAL REPLICATION. TREATMENT OF THESE MICE WITH COX2 INHIBITOR NOW PREVENT THIS TRANSMIGRATION, ALLOWS THE TISSUE TO REGENERATE, REPAIR ITSELF, AND ALLOWS INFECTION TO RESOLVE. SO COX2 INHIBITION EXPRESSES EPITHELIA TRANSMIGRATION BY NIGHT NEUTROPHILS AND ALLOWS INFECTION TO RESOLVE. THERE HAVE BEEN CLINICAL TRIALS LOOKING AT TREATING INDIVIDUALS WITH COX2 INHIBITORS. 70 WOMEN CAME IN WITH UTI, HALF TREATED WITH BIB IBUPROFEN OR CIPRO, WITH IDENTICAL RESULTS, CHANGING THE COURSE OF INFECTION, WE'RE HOPING TO DO A BIGGER TRIAL TO LOOK AT THIS MORE CAREFULLY. SUMMARIZING INFECTION CAN LEAVE MOLECULAR IMPRINT ON BLADDER IN FORM OF REMODELED MEMBRANE, PROTEIN REMODELING ON THE MEMBRANE, AS WELL AS ALTERED TRANSCRIPTOME. THIS CAN PREDISPOSE TO CHRONIC RECURRENT INFECTION. AND SO AT COX2 INHIBITION CAN BLOCK THIS AND LATER ON I'LL TALK ABOUT HOW VACCINATION CAN ALSO PROTECT AGAINST RECURRENT UTI. AS I MENTIONED IN THE BEGINNING ULTIMATE RESERVOIR FOR BACTERIA ARE IN THE GUT. BACTERIA GET SHED FROM THE GUT, COLONIZED PERIURETHRAL AREA, ASCEND IN BLADDER TO CAUSE UTI. THE QUESTION IS, WHAT ARE THE POPULATION DYNAMICS OF UPEC IN THE GUT, BEFORE DURING AND AFTER UTI, HOW DOES THE GUT MICROBIOTA INFLUENCE UTI SUSCEPTIBILITY, QUESTIONS NO ONE EVER ASKED, THE INTERACTION BETWEEN MICROBIOTA AND SUSCEPTIBILITY TO UTI. INDIGENOUS AND METABOLIC ATTRIBUTES, HAD TO EVOLVE ON OUR OWN, HEALTHY MICROBIOTA SERVES A ROLE, IN THE GENERATION OF IMMUNE BALANCE THAT LIMITS INFLAMMATION COMBATING COLONIZATION FROM UNWANTED PATHOGENS, COLONIZATION RESISTANCE, WHAT'S KEEPING UPEC OUT OF THE GUT RESERVOIR. ANTIBIOTIC TREATMENTS BREAK DOWN THIS COLONIZATION RESISTANCE THOUGHT TO EXPOSE INDIVIDUALS TO INCREASED RISK OF OPENING UP NICHES IN THE GUT WHICH ALLOWS PATHOGENS TO EXPAND. SO I WANT TO TALK ABOUT HOW WE'RE LOOKING AT THE MOLECULAR BASIS OF THIS GUT URINARY TRACT ACCESS IN URINARY TRACT INFECTION. WE TOOK UP A COLLABORATION WITH ASHLEY EARL AND HER GROUP AT THE BROAD INSTITUTE. THESE ARE EXPERIMENTS WE'VE BEEN DOING WITH THIS. RECRUITED 28 WOMEN INTO THE TRIAL, 14 WITH HISTORY OF INFECTION, 14 HEALTHY CONTROLS. AT ENROLLMENT COLLECT URINE, FECES, SERUM, AT TIME POINTS AND EPISODES, POST ANTIBIOTIC TREATMENT. WE GOT 19 UTI EVENTS DURING THIS TRIAL. COLLECTED 387 FECAL SAMPLE, 47 URINE, 47 BLOODS. SO WHAT ASHLEY AND HER COLLEAGUES DID WAS METAGENOMIC ANALYSIS ON THESE FECAL SAMPLES, AND WHAT THEY FOUND IS THAT RECURRENT UTI WOMEN HAVE A LOWER DIVERSITY IN THEIR MICROBIOTA THAN THE HEALTHY CONTROLS. SO THERE'S THIS DECREASE IN SPECIES RICHNESS IN THE MICROBIOTA OF THE RECURRENT UTI GROUP, LESS STRAINS IN THE MICROBIOTA, ALSO DEPLETE IN THESE STRAINS KNOWN TO BE ASSOCIATED WITH HEALTHY MICROBIOTA, LIKE FECAL BACTERIUM, SO WE CURRENT UTI IS ONE OF THE GROWING NUMBER OF HUMAN DISEASES ASSOCIATED WITH IMBALANCE OF COMPLEX MICROBIAL COMMUNITIES IN THE GUT. FURTHERMORE AT THE TIME OF UTI WHAT WE'RE SEEING IS THERE'S THIS BLOOM OF E. COLI IN THE GUT. E. COLI BLOOMS IN THE GUT ARE COINCIDING WITH URINARY TRACT INFECTION. SO PUTTING THIS ALL TOGETHER WE'RE BEGINNING TO SEE THAT A HEALTHY GUT HELPS PRECLUDE UPEC FROM OCCUPYING GUT AND ESTABLISHING RESERVOIR WHICH NOW IS GOING TO PREVENT RECURRENT UTIs. DUE TO SOME SORT OF MOLECULAR INSULT LIKE ANTIBIOTICS OR ANOTHER PERTURBATION, IT ALLOWS UPEC TO GAIN HOLD IN RESERVOIR, BLOOM AND THIS ALLOWS SEEDING OF THE URINARY TRACT. WE'RE ALSO INTERESTED IN LOOKING HOW THIS MICROBIOTA INTERACTS WITH IMMUNE FACTORS ALSO POSSIBLY TO PRE-PREDISPOSE URINARY TRACT TO INFECTION. AS THE NUMBER OF RECURRENT UTIs INCREASE, THE SPECIES RICHNESS DECREASES, WHICH SETS UP INDIVIDUALS FOR RECURRENCES, VICIOUS CYCLE, PREDISPOSING TO OTHER PROBLEMS MOST LIKELY. SO THIS ALL MAKES US INTERESTED IN HOW DOES UPEC COLONIZE THE GUT? THAT'S NEVER BEEN LOOKED AT BEFORE. CAITLIN SPALDING BEGAN TO LOOK, APPROACH WAS TO MUTATE ALL OF THE DIFFERENT PILI FOUND IN THE GENOME OF THIS PARTICULAR ISLET, UTI 89 AND COMPETES WILD TYPE WITH MUTANTS IN THE GUT. AND SO THE PROTOCOL SHE USES IS TREATS MICE WITH STREPTOMYCIN TO REDUCE COLONIZATION RESISTANCE I WAS TALKING ABOUT, THEN GAVAGE WITH UTI 99 AND YOU CAN SEE THIS RESULTS IN GOOD COLONIZATION OF THE GUT, ILIUM CECUM AND COLON. NOW IN HER COMPETITION STUDIES SHE FINDS THE TWO ADHESIONS THAT ARE MOST IMPORTANT COLONIZATION OF THE GUT ARE TYPE 1 PILI ALSO IMPORTANT IN BLADDER AS WELL AS SO CALLED F 17 LIKE PILI WITH THE TIP I TIP KNOWN AS UCLD. WHAT WE DID WAS TO OVERLAY COLONS WITH PURIFIED ADHESIONS, AND WE SEE FIMH IN RED BINDS TO UPPER PART OF THE CRIPS, AND SEEM TO BE BINDING TO OLIGOSACCHARIDES, TREATMENT WITH PNCH ABOLISHES, UCLD BINDING TO LOWER PARTS OF THE CRIPS WITH THIS RED STAINING HERE, SEEMS TO BE BINDING ONLY OLIGOSACCHARIDES, TREATMENT WITH OLIGO GLYCOSIDASE. WITH CRIPS IT INDICATES MAYBE ADHESIONS COULD PULL BACTERIA OUT OF THE LUMEN OF THE GUT INTO THESE CRYPTS WITH LESS COMPETITION IN REGARD TO ACQUISITION OF NUTRIENTS. THIS IS A BUSY SLIDE. I WANT TO MAKE ONE POINT, AND THAT IS IN E. COLI WHERE DO YOU FIND THESE F 17-LIKE PILI? OUTER CIRCLE ARE 33 DIFFERENT PILI ENCODED BY NEURO PATHOGENIC E. COLI, CONCENTRIC RINGS, THE POINT IS THESE F17-LIKE PILI ARE RESTRICTED. ANOTHER BUSY SLIDE TO MAKE THE POINT, PHYLOGENETIC DEPICTION, WHAT WE'RE SEEING IS THESE F-17-LIKE PILI BLUE ARE MOST RELATED TO ADHESIONS FOUND EXCLUSIVELY IN INTESTINAL E. COLI, AND INTESTINAL PATHOGENS LIKE THE F17 PILI. SEEMS UPEC STALLED THIS F17 ADHESION FROM INTESTINAL PATHOGENS AND THEN IT'S BEEN EVOLUTIONALLY FINE TUNED, WHAT DO YOU MEAN BY EVOLUTIONARY FINE TUNING? ROGER KLEIN CRYSTALLIZED THIS UCLD ADHESION, AND HERE'S THE STRUCK TEAR HERE AND FOUND EVEN THOUGH THE AMINO ACID SEQUENCES BETWEEN THIS ADHESION AND INTESTINAL ADHESION ARE VERY DIFFERENT, THESE TWO STRUCTURES ARE PRETTY MUCH SUPERIMPOSABLE ON ONE ANOTHER. WE KNOW WHAT THE RECEPTOR IS FOR THE F17 ADHESION. THAT'S THE INTESTINAL ONE, GLUCOSAMINE, WE DON'T KNOW WHAT IT IS IN UCLD, BINDING PROCESS IN THE SAME LOCATION, POINTING TO THIS IDEA THAT UPEC ACQUIRED THIS ADHESION FROM INTESTINAL PATHOGENS IS EVOLUTIONARY FINE TUNED TO ALLOW ASYMPTOMATIC COLONIZATION OF THE GUT RESERVOIR. LOOK AT THIS CLINICALLY, THIS ADHESION IS ONLY PRESENT IN 11% OF ALL E. COLI. WE WONDERED WHAT ABOUT IN STRAINS CAUSING RECURRENT UTI? ENROLLED 14 PATIENTS, COLLECTED STRAINS ACROSS RECURRENCES, DID COMPARATIVE GENOMIC ANALYSIS AGAIN WITH ASHLEY EARL AT THE BROAD AND FOUND 13 OUT OF 14 OF THE WOMEN WITH RECURRENT UTI ENCODED THIS ADHESION SUGGESTING IT MIGHT BE ASSOCIATED WITH UPEC PERSISTENCE IN WOMEN PROMOTING MAINTENANCE OF THIS INTESTINAL RESERVOIR. ALL RIGHT. NOW WHAT I WANT TO TURN TO AND END WITH HOW WE'RE TRYING TO APPLY ALL THIS INFORMATION AND KNOWLEDGE IN THESE STUDIES, TO TRY TO TRANSLATE THESE BASIC SCIENCE ADVANCES INTO ANTIBIOTIC-SPARING THERAPEUTICS, AN IMPORTANT ISSUE RELATING TO WOMEN'S HEALTH, ANTIBIOTIC RESISTANCE IS RISING AT ALARMING RATES, WE'RE REACHING TIPPING POINT, BECOMING IMPOSSIBLE TO TREAT CERTAIN INFECTIONS EVEN URINARY TRACT INFECTIONS. NUMBER ONE USE OF FLUOROQUINOLONES, LAST RESORT ANTIBIOTIC, IT'S NOW FRONT LINE ANTIBIOTIC, THERE'S 10 MILLION PRESCRIPTIONS WRITTEN EVERY YEAR OF FLUORO QUINOLONES TO TREAT URINARY TRACT INFECTIONS. IT'S NO WONDER THAT MULTI-DRUG RESISTANCE IS RISING, TREATMENT WITH BROAD SPECTRUM IS CREATING DYSBIOSIS IN THE GUT WHICH I TOLD YOU PREDISPOSES TO UTI AND OTHER CONDITIONS. SO WE'RE ASKING HOW CAN WE USE THIS BASIC SCIENCE TO TRY TO DESIGN ANTIBIOTIC-SPARINGATION. I'VE TOLD YOU FIMH PLAYS A ROLE IN ALL ASPECTS OF INFECTION CYCLE, YOU VACCINATE WITH FIMH, BUILD UP ANTI-FIMH ANTIBODIES TO BLOCK COLONIZATION, THIS MAY BLOCK INFECTION. A SMALL BIOTECH COMPANY LICENSED THIS TECHNOLOGY AND THEY HAVE JUST COMPLETED A PHASE 1A, 1B STUDY, TO MEASURE IgG RESPONSE AND DURATION AND SUSTAINABILITY. THERE WERE 67 WOMEN ENROLLED, IN SIX COHORTS, FIRST FOUR COHORTS WITH NO HISTORY OF UTI, FIVE AND SIX HAD HISTORY OF RECURRENT UTIs. SO THIS IS THE RESULT FROM STUDY. IN COHORT FIVE, PRE-FIMH IMMUNITY, 39 TOTAL UTI EVENTS. COHORT 6, 27 UTI EVENTS. PRE-FIM IMMUNITY. POST, THERE WAS 87% REDUCTION IN UTI CAUSED BY E. COLI AND KLEBSIELLA. EIGHT PATIENTS ARE NO UTI. THESE PROMISING DATA LED TO THE FDA APPROVING COMPASSIONATE USE OF THIS VACCINE, IN WOMEN WHO ARE, FOR EXAMPLE, IN THE FIRST WOMAN WHO HAS 73-YEAR-OLD WOMAN, RECURRENT UTI BY E. COLI RESISTANT TO STANDARD OF CARE, EXHAUSTED OPTIONS, FAILED PROPHYLAXIS WITH ORAL AMP SILLEN, RESISTANT, FAILED PROPHYLAXIS, BECAME RESISTANT, ENDED UP WITH UTIs CAUSED BY ESBL STRAINS, FINAL OPTION PUT HER ON IV IRBIPENTUM, NOW ON VACCINE, PRIOR HAD 20 RECURRENT UTIs, POST IMMUNITY HAD NO UTIs CAUSED BY E. COLI OR KLEBSIELLA. BASED ON PROMISING RESULTS, THOMAS HOOTEN IN MIAMI RECEIVED APPROVAL TO EXPAND COMPASSIONATE USE PROGRAM, WE'RE HOPING TO DO A FIMH TRIAL AT WASH U AND TAKE PATIENTS AND ISOLATE B CELLS AND LOOK AT MONOCLONAL ANTIBODIES AND BEGIN TO LOOK AT THE MECHANISM OF ACTION OF THESE ANTIBODIES AND EFFECT ON GUT MICROBIOTA. ANOTHER STRATEGY THAT WE'VE BEEN TAKING IS TO DESIGN MANNOSE ANALOGS, MANOCIDES THAT BIND TO FIMH WITH A MILLION MORE POTENCY THAN NATURAL RECEPTOR, AND THEY BLOCK COLONIZATION OF E. COLI TO THE URINARY TRACT, TO THE BLADDER. AND WE'VE DONE OVER THE YEARS THOUSANDS OF COMPOUNDS BASED ON CHEMISTRY, BIG BREAKTHROUGH WAS CHANGING THIS LINKAGE TO C, BECAUSE THE C MANOCIDES PERSIST IN THE BLADDER FOR LONG PERIODS OF TIME AND HAVE INCREASED POTENCY AND EFFICACY. THE IDEA IS MANNOSIDES BLOCKS COLONIZATION AND THEREFORE CAN ACT INSTANTANEOUSLY, RELEASE BACTERIUM FROM EPITHELIUM AND GET ELIMINATED FROM URINARY TRACT. WE'VE STARTED A COMPANY, NOW HAVE A WONDERFUL COLLABORATION WITH GLAXOSMITHKLINE, AND HOPING TO MOVE THESE COMPOUNDS INTO CLINICAL TRIALS. THIS IS JUST THE DATA OF SOME, HOW THEY WORK, PROPHYLACTICALLY. ORALLY BIOAVAILABLE. AND SO PROPORTIONS AFTER SIX HOURS YOU GET FOUR LOG REDUCTION IN CFU, THEY ARE WORKING FASTER THAN ANTIBIOTIC PROBABLY BECAUSE MECHANISM OF ACTION IS INSTANTANEOUS, ONCE THEY BIND THEY RELEASE BACTERIA. THREE DIFFERENT TREATMENTS MORE OR LESS ELIMINATE INFECTION. THEY WORK AGAINST DRUG RESISTANT STRAINS, MECHANISMS TARGET FIMH, CAN'T TREAT WITH TRIMETHPRINE BUT MANNOSIDE WORKS. COULD THAT AFFECT THE RESERVOIR? CAITLIN SAW THE PHARMACOKINETICS WERE GOOD ENOUGH TO USE, THE DRUG STAYED IN INTESTINE AT LEVELS ABOVE CONCENTRATIONS REQUIRED TO INHIBIT COLONIZATION FOR EIGHT HOURS AND USES STAIN PROTOCOL, TREAT THE MICE WITH STREPTOMYCIN AND ONE DAY LATER GAVAGE WITH E. COLI AND THEN DAY 3, THREE TREATMENT WAS MANNOSIDES. WHAT SHE SEES IS A 98% REDUCTION IN UPEC IN THE FECES, CECUM AND COLON. MANNOSE HAS NO EFFECT, YOU NEED HIGH AFFINITY INTERACTION TO GET THIS EFFECT. WHEN WE LOOK AT EFFECT ON MICROBIOTA STRUCTURE, AS I'VE MENTIONED SEVERAL TIMES ANTIBIOTICS DESTROY MICROBIOTA. CIPROFLOXACIN, YOU SEE THIS EFFECT. TREATMENT WITH MANNOSIDE HAS NO EFFECT ON THE STRUCTURE, TAKING OUT THE BAD GUYS, TAKING OUT UPEC. SEEMS MANNOSIDE CAN SELECTSIVELY DEPLETE UROPATHOGENNIC E. COLI OUT OF THE INTESTINE, SO THEY CAN SIMULTANEOUSLY REMOVE THIS RESERVOIR WHILE ALSO TREATING AN INFECTION, THE REASON I'M EXCITED ABOUT THIS IS BECAUSE IF WE CAN REMOVE THE RESERVOIR WE SHOULD BE ABLE TO REDUCE RATE OF RECURRENT UTIs, REDUCING DEPENDENCY ON ANTIBIOTICS. AND THAT WOULD BE I THINK A REALLY GREAT ACCOMPLISHMENT. SO, I'LL LEAVE YOU WITH THIS. PATHOGENIC BACTERIA CAUSING PLETHORA OF DISEASES RANGING TO URINARY TRACT INFECTION, ONE THING THEY HAVE TO DO AT SOME POINT IS COLONIZE A SURFACE. SO WE'RE HOPING TO REVOLUTIONIZE THROUGH DISSECTION OF HOST-PATHOGEN INTERFACE TO PRODUCE ANTIBIOTIC-SPARING THERAPEUTICS. SO I JUST HAVE A DISCLOSURE, I'M PART OWNER OF FIBRION AND COULD BENEFIT IF THIS WORKS. I WORK ON THE FEMALE SIDE, I FORGOT TO MENTION, THE SCORE INSPIRED US TO LOOK AT SEX DIFFERENCES. DR. HANSTEAD, PARTS OF PROJECT 2, IS NOW LOOKING -- BECAUSE OF THE WISDOM OF ORWH WE STARTED THESE PROGRAMS, NOW LOOKING AT MALE -- EFFECTS OF MALE -- MALES DON'T GET UTI VERY OFTEN BUT WHEN THEY DO IT'S SEVERE, AND ELDERLY MALES AND YOUNG BOYS GET THEM. I'LL JUST SHOW YOU ONE BRIEF SNIPPET OF WHAT HE'S FINDING, RATHER REMARKABLE. WHEN YOU LOOK AT MALE VERSUS FEMALE NOW TWO WEEKS POST INFECTION, YOU GET THIS DRAMATIC OCCURRENCE OF SEVERE KIDNEY INFECTION IN THE MALES COMPARED TO FEMALES. CASTRATE MALES, YOU DON'T GET THIS SEVERE KIDNEY INFECTION. AND IF YOU TREAT FEMALES WITH ANDROGEN YOU GET SEVERE KIDNEY INFECTION COMPARED TO UNTREATED. AND SO HE'S DEVELOPING ANIMAL MODELS NOW TO LOOK AT RENAL SCARRING, FOLLOWING ANTIBIOTIC TREATMENT AND PIE LOW NEPHRITIS, DISSECTING INTERACTIONS, SO IT'S A REALLY EXCITING PERIOD TO LOOK AT WHAT WE'RE LEARNING WITH SEX DIFFERENCE RESEARCH, IN THE CASE OF URINARY TRACT INFECTION. SO THIS IS THE MOST -- ONE OF THE MOST IMPORTANT SLIDES PEOPLE HAVE DONE THE WORK, TRIED TO MENTION THEIR NAMES, AND THANK YOU SO MUCH, OFFICE OF RESEARCH OF WOMEN'S HEALTH, NIDDK, NIAID, AND THE PROGRAM AND SPECIAL ACKNOWLEDGMENT TO ASHLEY EARL AND HER GROUP AT THE BROAD INSTITUTE. THANKS VERY MUCH. [APPLAUSE] >> THANK YOU SO MUCH, SCOTT. WE HAVE TIME FOR ONE QUESTION FOR DR. HOLTGREN. LET'S START WITH DR. MISUR,I, WE'LL DO THREE SHORT QUESTIONS. >> THANK YOU. THIS IS SUCH ELEGANT WORK. JUST A PLEASURE TO HEAR YOU PRESENT IT. I HAVE A QUESTION THAT'S MAYBE A LITTLE BIT OF A REACH BUT I'M CURIOUS HOW ESTROGEN FITS INTO YOUR MODEL. THE REASON I RAISE IT IS BECAUSE MY COLLEAGUES IN GYNECOLOGY TELL ME THEY FREQUENTLY USE VAGINAL ESTROGEN APPLICATION AND IT WORKS IN TERMS OF HELPING WITH UTIs AND CHRONIC UTIs. ALSO BECAUSE I KNOW THERE ARE ANIMAL MODELS THAT HAVE SHOWN THAT IF YOU ENGINEER ANIMALS GENETICALLY, YOU CAN INDICATE CLEARLY THAT WITH OVEREXPRESSION OF ESTROGEN RECEPTORS THESE ANIMALS CLEAR E. COLI FASTER IN THEIR URINE AND DON'T GET UTIs. IT INTERESTS ME HOW YOU WOULD FIT ESTROGEN AND HORMONES INTO YOUR MODEL. >> I MEAN, THAT'S MORE QUESTION FOR DR. HUNTSTAD, BUT WHO IS LOOKING AT EXACTLY THAT. BUT ONE THING, ESTROGENDD YOU MAY KNOW MORE BEEN THEY, IT'S CONTROVERSIAL. SOME PHYSICIANS AREN'T QUITE AS SOLD ON ESTROGEN AS OTHERS, BUT IT'S AFFECTING VAGINAL MICROBIOTA, SO THESE INFECTIONS ARE ASCENDING, FROM THE GUT, VAGINA, URINARY TRACT. AND SO THERE ARE PAPERS THAT DESCRIBE ONE EFFECT OF ESTROGEN IS PART OF THIS REGENERATION PROCESS, JUST LIKE IN THE BLADDER ONE OF THE POTENT INNATE DEFENSES IN THE BLADDER IS EXFOLIATION. AND SO THESE CELLS WHEN THEY GET COLONIZED UNDERGO APOPTOSIS AND SLOUGH OFF. AND SO THEY ARE SLOUGHING OFF INFECTED CELLS, THEN THEY GET ELIMINATED. AND SO THAT'S A POTENT INNATE DEFENSE. I THINK SOME PEOPLE SUGGEST THAT THE SAME THING IS HAPPENING WITH ESTROGEN TREATMENT IN THE VAGINA, SLOUGHING OFF CAN HELP GET RID OF INFECTED CELLS. A FASCINATING QUESTION THAT DESERVES ATTENTION. >> DR. BREWSTER >> I LIKE THE IDEA OF TERMINATING UPEC COLONIES, DO YOU HAVE THOUGHTS OF HOW DISTURBING THE MICROBIOTA OF THE GUT MIGHT BE THE DO YOU DOWNSTREAM EFFECT, COLON HEALTH, COLON CANCER. >> THAT'S A GREAT QUESTION. AND THE ADVANTAGE OF, AS I SEE IT, ADVANTAGE OF THESE MANNOSIDES, SELECTIVELY DEPLETING ONLY THE PATHOGEN, LEAVING STRUCTURE OF MICROBIOTA INTACT. ANTIBIOTIC YOU'RE WIPING EVERYTHING OUT. MANNOSIDE IS ONLY TAKING OUT THE PATHOGEN AS WE SEE IT AT THIS POINT. SO IT'S AN ADVANTAGE. YOU'RE LEAVING THE MICROBIOTA STRUCTURE INTACT THAT ALLOWS IT TO INTERACT WITH IMMUNE SYSTEM AND SET UP A HEALTHY GUT, WHICH CAN ALLOW FOR NUTRIENT ACQUISITION AND SO FORTH. YOU STILL HAVE ALL OF THE MEMBERS, STILL HAVE THE DIVERSITY LEFT, AFTER TREATMENT WITH MANNOSIDE. >> THE PATHOGEN. >> YES. SO THAT'S GONE. >> RIGHT. THE QUESTION, DO WE KNOW WHETHER THAT'S THAT SPECIFIC PATHOGEN HAS A -- IT'S NOT A PATHOGEN IN EVERYONE. >> IT'S A GOOD QUESTION. IT'S E. COLI. IN THAT 16 S RNA YOU STILL LEAVE BEHIND E. COLI. WE HAVE MARKED UPEC, THAT GETS DEPLETED. NORMAL E. COLI IS STILL THERE. WE DON'T KNOW WHY THE MANNOSIDE IS NOT AFFECTING NORMAL E. COLI BUT ONLY THE UROPATHOGEN, OUR SUSPICION IT HAS HIGH LEVELS OF FIMH, THE TARGET FOR THE DRUG. IT REALLY -- IT'S SOMETHING WE LOOK INTO, WE'RE PROPOSING TO LOOK INTO THIS, WHAT IS THE EFFECT, NORMAL PHYSIOLOGY, WHETHER IT'S VACCINE OR MANNOSIDE OR ANTIBIOTIC. NORMAL PHYSIOLOGY OF THE GUT BASED ON WHAT I'VE SEEN SO FAR. >> BEAUTIFUL WORK. QUICKLY, YOU STARTED OUT TALKING ABOUT ANTIBIOTIC AND HOW MUCH YOU USE, INCLUDING OTHER EPITHELIAL SURFACES, I WONDER THESE ARE SUCH BEAUTIFUL IDEAS FOR REDUCING USE OF ANTIBIOTICS, COULD YOU JUST COMMENT ON HOW APPLICABLE THEY MAY BE TO OTHER EPITHELIAL SURFACES, DIFFERENT ORORGANISMS, MANNOSIDE ITSELF OR VACCINATION CONCEPT TO THOSE. >> IT'S A GREAT QUESTION. THANK YOU VERY MUCH FOR THAT. I THINK I'M VERY EXCITED, IT'S POTENTIALLY BROADLY APPLICABLE, AS I SHOWED IN THE LAST SLIDE, ALL BACTERIAL PATHOGENS AT SOME POINT COLONIZE THE SURFACE, WHETHER IT'S OTITIS MEDIA, GONORRHEA, YOU NAME IT, THEY HAVE TO COLONIZE TO CAUSE DISEASE. COLONIZATION IS BASED ON A DIFFERENT ADHESIONS EXPRESSED BY DIFFERENT PATHOGENS AND RECEPTORS. SO BY UNDERSTANDING HOW RECEPTOR -- CHEMICAL SPECIFICITY, ONE CAN DESIGN MOLECULES TO INHIBIT THAT. WE'RE ACTUALLY EXPANDING OUR IDEA, THIS IDEA LOOKING AT KIDNEY INFECTION, SO BACTERIA CAUSING KIDNEY INFECTIONS ARE BINDING TO SOMETHING CALLED GLOBAL SERIES OF GLYCOLIPIDS, BIND TO A DIGALACTOCIDEE, PSEUDOMONAS, BY UNDERSTANDING STRUCTURAL BASIS, HIGH AFFINITY GALACTOCIDE, THERE'S POTENTIAL TO LOOK AT THIS ELSEWHERE. >> JANINE, CAN I ASK ONE QUESTION? >> QUICKLY. >> I'LL ASK A QUESTION THAT MIGHT BE CONSIDERED SOMEWHAT IMPOLITE. THAT IS, THIS WORK, WHICH IS REALLY INTERESTING, AND CERTAINLY HAS A GREAT PUBLIC HEALTH AND POTENTIAL FOR GREAT PUBLIC HEALTH AND CLINICAL CARE, INVESTED BY NIH, AND NIAID, SO BUT IT'S NOW MOVED INTO THE PRIVATE SECTOR. A COMPANY WILL DEVELOP THESE PRODUCTS. IF THEY ARE WILDLY SUCCESSFUL, THEY MIGHT BE WILDLY EXPENSIVE. AND AS WE'VE SEEN PARTICULARLY WITH BIOLOGIC PRODUCTS, THEY CAN BE WILDLY EXPENSIVE. IT MAY NOT BE YOUR ABILITY TO ANSWER OR SOLVE THE PROBLEM, BUT ARE THERE IN THE RELATIONSHIPS BETWEEN THE NIH, UNIVERSITY, INVESTIGATORS AND COMPANIES IS THERE SOME THOUGHT AND PLANNING TO MAKE SURE THIS ACTUALLY IS AN INVESTMENT OF PUBLIC DOLLAR AND PUBLIC RESEARCH THAT ACTUALLY COMES BACK TO BENEFIT THE PUBLIC? >> I THINK GREAT POINTS TO RAISE AND DISCUSS. BUT I THINK THE GOAL OF NIH, ORWH, THEY WANT TO SEE OUR RESEARCH TRANSLATED TO IMPROVE PUBLIC HEALTH. AND THAT'S THE WAY IT WORKS. SO, THE BENEFIT TO THE PUBLIC IS REDUCED DEPENDENCY ON ANTIBIOTICS, IMPROVED HEALTH, THE COST STRUCTURE OF THESE THINGS IS SOMETHING THAT I AM NOT PRIVY TOO. IT'S NOT TRUE WE'RE MOVING TO THE PRIVATE SECTOR. ONE THING HAS MOVED. AND THEN ALL OF THESE OTHER THINGS ARE STILL BEING INVESTIGATED IN THE LABORATORY. >> COMPLICATED STORY, AND I THANK YOU FOR RAISING THE ISSUE. BEFORE WE ADJOURN I'LL HAVE THE EXEC SEC, ALSO DEPUTY DIRECTOR GIVE ANNOUNCEMENTS. KNOWLEDGE AND UNDERSTANDING, ONCE WE GET AN UNDERSTANDING THAT THERE MIGHT BE VERY DIFFERENT STRATEGIES FOR ELIMINATING PATHOGENIC BACTERIA, SCIENTISTS HAVE PROVEN TO BE INCREDIBLY CREATIVE, INGENIOUS IN DEVELOPING MULTIPLE WAYS TO DISRUPT WHAT WE NOW UNDERSTAND IS A PATHWAY FOR PATHOGENESIS. SO WE WOULD HOPE THAT THE KNOWLEDGE IS CERTAINLY BROAD AND FREELY AVAILABLE TO EVERYONE. AND OF COURSE NIH HAS MULTIPLE STRATEGIES LIKE SBIR AND STTR TO SUPPORT TECHNOLOGY TRANSFER PROJECTS TOO. THANK YOU VERY MUCH FOR YOUR PRESENTATION. [APPLAUSE] AND MISS SPENCER? >> WHAT A WONDERFUL MORNING WE'VE HAD. AND APPRECIATE YOU ALL JOINING US. I WANTED TO TAKE A MOMENT BEFORE WE BREAK FOR OUR LUNCH TO RECOGNIZE DR. MARJORIE JENKINS WHO JOINED US FROM THE FDA, OUR COLLEAGUE AND FRIEND AND SUPPORTER. ALSO WANT TO RECOGNIZE THE FACT WE'VE ALSO BEEN JOINED BY THE SOCIETY FOR RESEARCH AND WOMEN'S HEALTH, WOMEN'S HEART ALLIANCE, HOWARD HOSPITAL, HOWARD COLLEGE OF MEDICINE, NATIONAL POLYCYSTIC OVARY SYNDROME ASSOCIATION, AND NATIONAL ACADEMIES OF SCIENCE. THANK YOU ALL FOR JOINING US FOR THIS VERY IMPORTANT MEETING AND WE TRULY DO APPRECIATE AND VALUE YOUR PRESENCE WITH US. NOW FOR THE GOOD THING THAT EVERYONE'S WAITING FOR, A BREAK AND TO HAVE LUNCH. OKAY. WE'RE GOING TO RECONVENE. THE ADVISORY COMMITTEE FOR RESEARCH ON WOMEN'S HEALTH. AND I'M PLEASED TO INTRODUCE OUR NEXT SPEAKER, DR. DIANA BIANCHI, EUNICE KENNEDY SHRIVER -- DIRECTOR OF THE EUNICE KENNEDY SHRIVER, DIRECTOR FOR 18 MONTHS NOW, PRIOR TO COMING TO NIH PRACTICED AT MEDICAL GENETICIST, EDITOR IN CHIEF OF PRENATAL DIAGNOSIS OF INTERNATIONAL SOCIETY FOR PRENATAL DIAGNOSIS, FOUNDED MOTHER/INFANT RESEARCH INSTITUTE AT TUFTS MEDICAL CENTER. RECIPIENT OF THE LANDMARK AWARD IN RECOGNITION FOR HER CONTRIBUTIONS TO GENETICS AND NEWBORN CARE, MAUREEN ANDREW AWARD FOR MENTORING. PLEASE WELCOME DR. DIANA BIANCHI TO GIVE US AN INSTITUTE UPDATE, INCLUSION OF PREGNANT AND LACK EIGHT LACTATING WOMEN. >> IT'S WONDERFUL TO BE AMONGST OLD FRIENDS I DIDN'T REALIZE I WOULD SEE TODAY AND NEW FRIEND. TALKING WITH JANINE WE REALIZED THIS BEFORE, EVIDENT WHEN I WAS TELLING HER WHAT I WAS TALKING ABOUT, HOW MUCH SYNERGY THERE IS BETWEEN NICHD AND THE OFFICE OF RESEARCH ON WOMEN'S HEALTH. AND I'M GOING TO TALK ABOUT SOME THINGS THAT ARE TIMELY AND THINGS WE'VE BEEN WORKING ON ACTIVELY DURING THE FIRST YEAR OF MY TENURE IN THIS POSITION. REALLY WHAT'S BUBBLED UP AS I'M GOING TO GET TO IN THE BEGINNING OF THE TALK IS THE IMPORTANCE OF INCLUDING PREGNANT WOMEN AND LACTATING WOMEN IN CLINICAL RESEARCH, SOMETHING WE'VE BEEN WORKING ON AS PART OF THE CURES ACT. YOU HAD A TALK THIS MORNING ON THE CURES ACT BUT THAT'S THE PRGLAC TASK FORCE. I'M GOING TO TALK ABOUT A CROWD SOURCING RESOURCE CALLED PREGSOURCE. I'LL TALK ABOUT OUR EFFORTS IN TRYING TO GET CHILDREN INCLUDED IN "ALL OF US," AND HOW AS A RESULT OF THAT PREGNANT WOMEN ARE BEING INCLUDED BUT THERE'S MORE WORK TO BE DONE. I HOPE TO EMPOWER AND MOBILIZE YOU. THEN THE BIGGEST PUBLIC HEALTH CRISIS OF OUR TIME RIGHT NOW IS OPIOID MISUSE, AND HOW THAT'S AFFECTING PREGNANT AND LACTATING WOMEN AND NEONATAL OPIOID WITHDRAWAL SYNDROME. THAT'S WHAT NOWs IS AND BRIEF WORDS ON THE STRATEGIC PLANNING PROCESS, ONGOING. I DON'T KNOW HOW MANY OF YOU HAVE BEEN IN THE NATIONAL PORTRAIT GALLERY, I STUMBLED UPON THIS PORTRAIT ONE DAY. OF COURSE, THE PERSON ON THE RIGHT HERE IS EUNICE KENNEDY SHRIVER, WHO HAS BEEN IN THE NEWS A LOT LATELY BECAUSE THERE'S A NEW BIOGRAPHY ABOUT HER WHICH I HAVEN'T YET, SHE AS A WOMAN WAS THE LEAST RECOGNIZED OF THE KENNEDYS, PROBABLY WITH THE MOST IMPACT. IN MY OFFICE THERE'S A PORTRAIT OF JOHN F. KENNEDY, HER BROTHER. NICHD WAS CONCEIVED OF BY EUNICE, AND SHE WAS THE ONE WHO KEPT NAGGING HER BROTHER TO GET AN INSTITUTE DEDICATED TO THE STUDY OF PEOPLE ACROSS THE LIFESPAN WITH A PARTICULAR EMPHASIS ON PEOPLE WITH INTELLECTUAL DISABILITIES. HER SON TIM SHRIVER IS ON OUR ADVISORY COUNCIL, I ASKED ABOUT A PORTRAIT OF HIS MOTHER FOR MY OFFICE, IT WOULD BE MORE APPROPRIATE. BUT I WAS VERY HAPPY TO SEE THIS PAINTING IN THE NATIONAL PORTRAIT GALLERY AND GOT PERMISSION FROM THE ARTIST TO SHOW IT. IT SHOWS EUNICE AND HER COMMITMENT TO CHILDREN OF ALL AGES AND THERE'S A YOUNG ADULT HERE WHO HAS DOWN SYNDROME. WELL, AGAIN, THIS THEME HAS BEEN PERCOLATING DURING THE PAST YEAR BECAUSE OF A NUMBER OF CURES ACT-RELATED ACTIVITIES THAT WE'VE BEEN INVOLVED IN. AND AS A RESULT OF THIS, IT REALLY BECAME CRYSTAL CLEAR WE ALL NEED AND YOU NEED TO JOIN US IN THIS EFFORT. WE NEED TO INCLUDE UNDERREPRESENTED POPULATIONS IN RESEARCH. SO CATHY SPONG, DEPUTY DIRECTOR AT NICHD, DID AN ANALYSIS OF PHASE 3 AND PHASE 4 CLINICAL STUDIES ON clinicaltrials.gov. AND SHOWED THAT 68% OF ONGOING CLINICAL TRIALS ARE EXCLUDING PREGNANT WOMEN. FOR LACTATING WOMEN, IT'S 47.3%, FOR CHILDREN IT'S 75%. INTELLECTUAL DISABILITIES AND PHYSICAL DISABILITIES, THERE ARE OTHER CORE POPULATIONS, THEY ARE NOT NECESSARILY EXCLUDED BUT A LOT OF TIMES PEOPLE AREN'T EVEN THINKING ABOUT THEM AS A SPECIFIC POPULATION. AND IF YOU PUT THOSE FIVE POPULATIONS TOGETHER, WE ARE EXCLUDING 58% OF THE TOTAL U.S. POPULATION. SO, WE NEED A CULTURE CHANGE, AND THAT'S GOING TO BE THE THEME OF MY TALK GOING THROUGH IT. NOW, YOU WOULD SAY, OKAY, THAT'S IN OTHER PARTS OF THE COUNTRY. IT TURNS OUT HERE WE ARE, NIH, HERE'S THE CLINICAL CENTER, LARGER RESEARCH HOSPITAL IN THE WORLD. IT TURNS OUT YOU CANNOT STUDY A HEALTHY PREGNANT WOMAN ON A PROTOCOL IN THE CLINICAL CENTER RIGHT HERE, RIGHT ACROSS THE STREET. NOW, WE UNDERSTAND THAT THEY DON'T WANT WOMEN WHO ARE SICK OR AT RISK OF DELIVERING A PREMATURE INFANT DELIVERING THERE BECAUSE WE DON'T HAVE THE SUPPORT STAFF FOR THE MOTHER OR THE BABY. BUT WHAT WE'RE TALKING ABOUT HERE RELATIVELY BENIGN NON-INVASIVE CLINICAL STUDIES, ULTRASOUND STUDIES, MRI STUDIES, METABOLIC STUDIES, AND THEY ARE NOT INVASIVE, SO WE ASKED THE QUESTION, WHY IS THAT? THE CERTAIN IS THAT THEY MIGHT DELIVER. SO, MY NEXT QUESTION WAS DOES THAT MEAN THAT PREGNANT WOMEN WHO WORK AT THE CLINICAL CENTER CANNOT WORK DURING THEIR PREGNANCY? THERE'S NO ANSWER FOR THAT. SO AFTER A LOT OF NAGGING, IT TURNS OUT IT'S REALLY JUST A HISTORICAL ARTIFACT, AND IT'S AN ANCIENT CULTURE. SO, A WORKING GROUP HAS BEEN FORMED TO EXAMINE THE BENEFITS AND RISKS OF HAVING HEALTHY WOMEN -- HEALTHY PREGNANT WOMEN WHO ARE HEALTHY PARTICIPATE IN RESEARCH PROTOCOLS. THIS IS PART, AGAIN, OF TRYING TO CHANGE THIS CULTURE THAT PREGNANCY IS NOT THIS GREAT MYSTERY, AND THERE'S A GOOD REASON TO HAVE A PROTOCOL IN PLACE FOR THE STAFF, OR PERHAPS THE PARTNER OF A MAN WHO IS UNDERGOING A PROTOCOL, LET'S SAY, FOR CANCER AND HIS PARTNER HAPPENS TO BE PREGNANT, THERE NEEDS TO BE PROTOCOL TOO IF THAT PERSON SITTING IN THE CLINICAL CENTER, JUST IF YOU HAVE AN EMERGENCY, THIS IS HOW WE'RE GOING TO DEAL WITH IT. SO, I MENTIONED THE CURES ACT OF THE PART OF THE CURES ACT WAS TO ESTABLISH A TASK FORCE ON RESEARCH SPECIFIC TO PREGNANT AND LACTATING WOMEN. THE MISSION OF THE TASK FORCE WAS TO ANALYZE FEDERAL EFFORTS AND PROGRAMS IN THIS, FUTURE RESEARCH COLLABORATION, ETHICAL ISSUES SURROUNDING INCLUSION OF PREGNANT AND LACTATING WOMEN IN CLINICAL RESEARCH, WHAT ARE THE BEST EFFECTIVE COMMUNICATION STRATEGIES WITH HEALTH CARE PROVIDERS AND THE PUBLIC, AND IT'S BEEN A TERRIFIC EXPERIENCE BEING ON THIS TASK FORCE, WHICH IS CHAIRED BY OUR DEPUTY DIRECTOR CATHY SPONG, AND THREE OF THE FOUR MEETINGS HAVE BEEN COMPLETED THE LAST ONE IS NEXT MONTH, AND AT THAT POINT WE'LL PUT TOGETHER A REPORT TO THE SECRETARY OF HEALTH AND HUMAN SERVICES, SECRETARY AZAR, AND TO CONGRESS. WHEN I TESTIFIED IN CONGRESS LAST WEEK, ONE OF THE THREE QUESTIONS THAT I WAS ASKED WAS ABOUT THIS. I WOULD SAY THAT ON THE PART OF THE FEMALE CONGRESS PEOPLE THERE'S GREAT INTEREST IN THIS AREA AS WELL AS ISSUES THAT AFFECT CHILDREN. SORRY. SO, IN THE FIRST TASK FORCE WE REVIEWED WHAT EXISTS IN THE LITERATURE WITH REGARD TO STUDIES, RANDOMIZED CLINICAL TRIALS, THAT HAVE BEEN PERFORMED IN PREGNANT WOMEN. AND THERE AREN'T A WHOLE LOT OF THEM. WHEN YOU THINK PREGNANCY OCCURS, MOST WOMEN WILL HAVE HAD AT LEAST ONE PREGNANCY IN THEIR LIFETIME, THERE AREN'T A WHOLE LOT OF STUDIES. AND THEY EITHER ARE IN BASIC SCIENCES, PHARMACOKINETICS, PHARMACODYNAMICS, POPULATION OR DATABASE STUDIES OR RANDOMIZED CLINICAL TRIALS. YOU DID SEE PRE-TERM PREVENTION OF PRE-TERM LABOR IS A BIG ONE, THAT'S BEING STUDIED ACROSS THE SPECTRUM. BUT IN TERMS OF SUBSTANCE ABUSE OR IN TERMS OF MENTAL HEALTH, THERE'S ALMOST NOTHING THAT'S BEING DONE. WE ALSO ASK INDUSTRY COLLEAGUES WHO ARE ON THE TASK FORCE AND CHRISTINA FROM NOVARTIS DID A STUDY LOOKING AT TRIALS INVOLVING BOTH LACTATING WOMEN AND PREGNANT WOMEN, IF THEY WERE COMPLETED, IF THEY WERE SUSPENDED FOR SOME REASON OR IF THEY ARE ONGOING. WHAT STRIKES ME ABOUT THIS PARTICULAR GRAPHIC IS THAT THERE'S ALMOST NOTHING IN LACTATION. IT IS A TOTAL DESERT IN TERMS OF STUDY OF ANY KIND. AND WE'VE HEARD FROM WOMEN WHO HAVE BEEN PARTICIPATING THEMSELVES IN THE TASK FORCE, AND REPORTING ON THEIR OWN PERSONAL EXPERIENCES. WE'VE HEARD ABOUT THEIR CHOICES THAT THEY HAVE EITHER HAD TO CHOOSE BETWEEN TAKING A MEDICATION WITH UNKNOWN RISK TO THEIR BABY, THEIR PEDIATRICIAN SAYS ASK OBSTETRICIAN, WHO SAYS ASK THE PEDIATRICIAN, NOBODY KNOWS THE ANSWER, OR IF THE WOMAN WANTS TO BREASTFEED DON'T TAKE THE MEDICINE TO BE PERFECTLY SAFE, PUTTING HER OWN HEALTH AT RISK, AND AREA WHERE THERE'S A HUGE GAP AND WE NEED TO DO MORE. PART OF THE TASK FORCE WE BECAME AWARE OF THE FACT THAT THERE WERE NO WHAT WE CALL RCDC CODES HERE AT NIH. WHEN I HEARD PEOPLE TALKING ABOUT RCDC IT SOUNDED LIKE SOMETHING OUT OF "STAR WARS." STANDS FOR RESEARCH CONDITION AND DISEASE CATEGORIZATION CODES. IT'S A DATABASE THAT ALLOWS FOR REPORTING ON SPECIFIC DISEASE CONDITIONS. SO THAT, FOR EXAMPLE, PATIENT GROUPS CAN FIND OUT HOW MUCH RESEARCH IS BEING DONE ON DOWN SYNDROME AND FOLLOW THE TRENDS. SO, IT REPORTS ON MORE THAN 280 TOPICS BUT UNTIL THIS YEAR PREGNANCY WAS NOT A TOPIC. CAN YOU BELIEVE THAT? SO, THERE IS A VERY RIGOROUS WAY THAT THEY GENERATE THE DATA. THERE'S KIND OF A LOBBYING EFFORT, THERE'S RATIONALE GIVEN FOR WHY THE CATEGORY IS NEEDED. IN THIS CASE OUR STAFF AT NICHD HAD TO GET THIS INFORMATION BECAUSE OF THE TASK FORCE. SO IT ALLOWED US TO GET THE CATEGORY ESTABLISHED, BUT WE DO NOT USE IT FOR BUDGETING. IT'S USED ON FUNDED ACTIVITIES TO REPORT TO CONGRESS AND TO WHOMEVER, IT'S A PUBLICLY AVAILABLE DATABASE. IT IS POSSIBLE THAT A PARTICULAR PROJECT WOULD BE PUT INTO MORE THAN ONE CATEGORY. BUT, WE WERE VERY EXCITED AS PART OF THE TASK FORCE TO BE ABLE TO GIVE SOME DATA TO THE MEMBERS OF THE TASK FORCE. SO IT TURNS OUT THAT WE GOT THREE NEW CATEGORIES. NONE OF THESE CATEGORIES WERE EVER ESTABLISHED PRIOR TO THIS YEAR. SO, NIH OVERALL IS FUNDING 683 PROJECTS ON PREGNANCY AT A TOTAL OF $319 MILLION. OUT OF A TOTAL OF, IN 17, ABOUT $34 BILLION. WE HAVE 27 INSTITUTES AND CENTERS, SO THE MAJORITY OF THEM ARE DOING SOMETHING RELATED TO PREGNANCY. THERE'S ALSO A CATEGORY ON MATERNAL HEALTH, AND THEN A NEW ONE ON BREASTFEEDING, LACTATION, AND BREAST MILK. THINK THE TAKEHOME MESSAGE IS THAT THERE IS A CONSIDERABLE AMOUNT OF RESEARCH GOING ON, ACROSS NIH. IT'S NOT IN ANY ONE SPECIFIC AREA. AND THERE'S A HALF A BILLION DOLLARS ON THESE AREAS. NICHD HAS THE MOST PROJECTS IN TERMS OF NUMBERS, BUT YOU CAN SEE THAT THERE ARE QUITE A NUMBER OF OTHER INSTITUTES INVOLVED. I ASSUME THAT THE OFFICE OF RESEARCH ON WOMEN'S HEALTH WOULD BE IN THE "OTHERS" CATEGORY. ANOTHER THING WE'VE DONE NOT IN RELATION TO THE TASK FORCE OR TO THE CURES ACT IS TRYING TO USE CROWD SOURCING. SO IF IT'S HARD ENOUGH FOR NIH TO DEFINE PREGNANCY AND REPORT ON PREGNANCY, WE KNOW THAT THERE IS NO SUCH THING AS A TYPICAL PREGNANCY AND WE GET A LOT OF QUESTIONS AS PHYSICIANS, YOU KNOW, ARE MY SYMPTOMS NORMAL, AM I GAINING TOO MUCH OR TOO LITTLE WEIGHT? SO PRIOR TO MY ARRIVAL HERE, THERE WAS A LOT OF WORK PUT IN TO ESTABLISHING THIS CROWDSOURCING RESOURCE CALLED PREGSOURCE. THOSE WHO WANT TO CAN GO ONLINE, IT'S MOBILE FRIENDLY, TO LOOK AT IT. IT'S MEANT AS WAY FOR PREGNANT WOMEN TO ENTER THEIR SPECIFIC DATA ON PREGNANCY EXPERIENCE, INCLUDING HOW MUCH THEY ARE SLEEPING AT NIGHT, WHETHER THEY HAVE NAUSEA AND VOMITING, HOW MUCH EXERCISE THEY ARE DOING, HOW MUCH WEIGHT THEY ARE GAINING, AND WHAT MEDICATIONS THEY ARE TAKING, WHICH IS HOW IT LINKS TO PRGLAC. BY GETTING INFORMATION, EACH WOMAN WILL GET HOW HER RESPONSES COMPARE TO THE ENTIRE DATASET, BUT IT WILL BE -- IT'S DE-IDENTIFIED AND WE CAN USE THAT INFORMATION TO BETTER UNDERSTAND WHAT A TYPICAL PREGNANCY EXPERIENCE CONSISTS OF AND THEN TO DESIGN STUDIES TO IMPROVE MATERNAL CARE. THE ENTIRE RESOURCE WAS DESIGNED WITH A NUMBER OF BOTH FEDERAL PARTNERS AS WELL AS FOUNDATIONS. AND WE'RE VERY GRATEFUL FOR ALL OF THEIR INPUT. THIS IS WHAT IT LOOKS LIKE. I MEAN, I HAVE TESTED, BY THE WAY, I SIGNED UP IN AS MISS EUNICE, THAT WAS MY TEST NAME. AND WHEN YOU GO IN, IT'S VERY USER FRIENDLY. YOU CAN CLICK ON ANY OF THESE LINKS, AND THEN YOU GET UPDATES AS WELL AS INFORMATION ABOUT OTHER PEOPLE. AND THEN IF YOU ARE NOT COMPLETELY HEALTHY AND YOU HAVE CERTAIN SYMPTOMS, FOR EXAMPLE IN THIS LINE IF YOU PUT IN THAT HAVE YOU GESTATIONAL DIABETES, FOR EXAMPLE, YOU WILL THEN GET TRIGGERD WITH ANOTHER SET OF QUESTIONS. AND THEN THERE'S ALSO THE CAPACITY TO LOOK AT THINGS POSTPARTUM, SO BOTH THE MOTHER, FOR EXAMPLE, IF SHE HAS POSTPARTUM DEPRESSION, QUESTIONS RELATED TO BREASTFEEDING, AND THEN HOW THE BABY IS DOING UP UNTIL 3 YEARS OF AGE. SO, IT'S JUST -- IT'S STILL IN A SOFT LAUNCH BUT AS OF THIS MONTH WE HAD 513 PARTICIPANTS ENROLLED. THEY ARE AT A VARIETY OF AGES, A VARIETY OF DIFFERENT BACKGROUNDS, AND SO FAR IT'S GOING QUITE WELL. NOW, INCLUSION ALSO MEANS INCLUSION IN ONE OF NIH'S BIGGEST PROJECTS, WHICH IS THE " ALL OF US" PERSONALIZED MEDICINE INITIATIVE. AND WHEN I FIRST ARRIVED, JUST ABOUT 18 MONTHS AGO, THERE WAS NO DISCUSSION ABOUT CHILDREN. THE CONCERN WAS, WELL, THERE ARE CONSENT ISSUES, AND WE'RE WORRIED ABOUT HOW TO FACILITATE THAT. WE'LL DEAL WITH THAT ONCE WE GET THINGS GOING FOR THE ADULTS. BUT, THIS IS ALSO BEING CONCEIVED OF AS THE PROJECT THAT'S GOING TO ENTAIL 60, 70, POSSIBLY 80 YEARS. THE MOST LOGICAL PEOPLE TO ENROLL ARE EITHER PREGNANT WOMEN OR CHILDREN WHO ARE JUST BEING BORN. SO FORTUNATELY, WE HAVE SOME SUPERSTAR PEDIATRICIANS CORRALLED INTO A SCIENTIFIC VISION WORKING GROUP, AND THEIR REPORT HAS JUST COME ONLINE. AND IT'S REALLY QUITE COMPREHENSIVE AND QUITE TERRIFIC, BUT THE THING I WAS MOST EXCITED ABOUT WAS THEY HAVE INCLUDED THE CONCEPT OF THE LIFE COURSE INTERGENERATIONAL PERSPECTIVE, BECAUSE IF WE KNOW NOTHING ELSE, WE KNOW THAT PREGNANCY IS A STRESS TEST FOR THE FUTURE HEALTH OF THE WOMAN, AFTER SHE COMPLETES HER PREGNANCY OR PREGNANCIES. SO HOW DO YOU DO DURING PREGNANCY IS A RISK FACTOR, IF YOU GET GESTATIONAL DIABETES, FOR INSTANCE, YOU'RE AT RISK OF DEVELOPING TYPE 2 DIABETES LATER ON. IF YOU HAD HYPERTENSION OR PRE-ECLAMPSIA YOU'RE THE INCREASED RISK OF CARDIOVASCULAR DISEASE AND STROKE, NOW VASCULAR DEMENTIA LATER IN LIFE. SO PREGNANCY IS A REALLY IMPORTANT LENS WITH REGARD TO WOMEN'S HEALTH. I'M PROBABLY PREACHING TO THE CONVERTED BUT IT'S A GOOD OPPORTUNITY TO SAY THAT. NOW, THE "ALL OF US" PROGRAM DEVELOPED SOME USE CASES, SO WHAT THESE ARE, THEY HAVE A DEMOCRATIC APPROACH TO TALKING ABOUT HOW THEY ARE GOING TO USE THE DATA THAT ARE GENERATED. THEY ARE GENERATING OMICS DATA, THEY ARE GENERATING ENVIRONMENTAL DATA. THEY ARE GENERATING MEDICATION EXPOSURES. THEY ARE GENERATING ALL KINDS OF HEALTH HISTORIES. NICHD STAFF PUT FORWARD SOME EXAMPLES OF CASES AND THEN THESE WERE SENT OUT ALONG WITH OTHER INSTITUTES AND CENTERS TO THE GENERAL PUBLIC WHO THEN VOTED ON THESE. AND THE ONES THAT NICHD PUT THROUGH, I PUT THE ARROWS NEXT TO THE ONES THAT MENTION THE MATERNAL EXPERIENCE, OR FECUNDITY IN FEMALES, FOR EXAMPLE. THESE PARTICULAR CASES DID QUITE WELL. AND BECAUSE WE MOBILIZE THE PEDIATRIC ADVOCACY COMMUNITIES, GOT A LOT OF VOTES, AND BROUGHT THE PEDIATRIC USE CASES ON TO THE RADAR SCREEN OF THE "ALL OF US" STAFF. I'M TELLING YOU THIS BECAUSE I THINK THAT THERE'S A GREAT OPPORTUNITY TO MAKE SURE THAT WOMEN'S HEALTH ISSUES ARE INCLUDED AS PART OF THIS MASSIVE PROJECT THAT HAS BEEN GIVEN QUITE A LOT OF MONEY THROUGH GENEROSITY OF CONGRESS. BUT WE KNOW THAT BY MOBILIZING OUR COMMUNITIES WE WERE ABLE TO GET THE PEDIATRIC CASES MORE ATTENTION. NOW INCLUSION, THIS IS THE LAST THING I'LL SAY ABOUT INCLUSION FOR NOW, BUT WE'RE VERY COMMITTED TO INCLUDING VOICE OF THE PARTICIPANT IN OUR ADVISORY COUNCILS, SO THIS IS SOMETHING WE'VE STARTED SINCE I'VE BEEN HERE, AND WE'VE JUST HEARD SOME REALLY AMAZING STORIES ABOUT HOW PEOPLE HAVE BEEN POSITIVELY AFFECTED BY RESEARCH THAT IS FUNDED BY NICHD, INCLUDING THE TOP THREE REALLY DO INVOLVE WOMEN'S HEALTH ISSUES, EVEN THOUGH THE FIRST ONE, THIS IS ANNIE RIBAS, PITUITARY TUMOR, HER MOTHER WAS TOLD SHE'S NOT FEEDING THE CHILD APPROPRIATELY, FEEDING CHILD TOO MUCH, MATERNAL ISSUE. TURNED OUT THE CHILD HAD A PITUITARY TUMOR THAT THEN RESPONDED TO SURGERY. EXCUSE ME. TARA SHAFER PRESENTED HER STORY AT A HUMAN PLACENTA PROJECT MEETING. WE'VE INVESTED ABOUT OVER $50 MILLION IN THE HUMAN PLACENTA PROJECT TO UNDERSTAND HOW THE PLACENTA IS FUNCTIONING REAL TIME AND NON-INVASIVE. BUT TARA EXPERIENCED A MISCARRIAGE AND TOLD THE ATTENDEES AT OUR MOST RECENT MEETING WHAT IT WAS LIKE TO BE TOLD LATE IN THE THIRD TRIMESTER HER BABY HAD STOPPED -- THE HEARTBEAT HAD STOPPED. SO VERY IMPRESSIVE REMINDER OF HOW WE NEED TO CHANGE THE WAY WE DELIVER INFORMATION. MEGAN CONNELLY IS A TWO-TIME SURVIVOR OF HODGKIN'S DISEASE, AND SHE HAS PARTICIPATED IN A PROTOCOL TO PRESERVE FERTILITY. WE'RE FUNDING INVESTIGATORS WHO REALLY HAVE ESTABLISHED THE FIELD OF ONCOFERTILITY. I MENTION THESE TO PUT A HUMAN VOICE ON EXPERIENCES OUR PARTICIPANTS ARE GOING THROUGH AND HOW THEY BENEFITED FROM THE RESEARCH. SO, I DON'T THINK ANYBODY HERE IS UNAWARE OF THE HEALTH AND FISCAL IMPACT OF OPIOID USE BUT YOU MAY NOT THINK ABOUT HOW IT AFFECTS PREGNANT WOMEN AND NEWBORNS. AS A RESULT OF PRGLAC WE KNOW PREGNANT WOMEN ARE TAKING THREE TO FIVE PRESCRIPTIONS DURING PREGNANCY, WE DON'T KNOW WHAT THEY ARE DOING TO THE WOMAN OR FETUS BUT WE KNOW THEY ARE TAKING THEM. WE ALSO KNOW THAT FOR A VARIETY OF REASONS, WOMEN ARE ON OPIOIDS BEFORE THEY GET PREGNANT AND THEY CONTINUE THEIR PREGNANCIES TAKING OPIOIDS. AND THAT HAS RESULTED IN A GREATER THAN FIVE TIMES INCREASE IN NEONATAL OPIOID WITHDRAWAL SYNDROME. IN 2012 NEARLY 22,000 INFANTS WERE BORN WITH NEONATAL OPIOID WITHDRAWAL SYNDROME IN THE UNITED STATES. THAT NUMBER HAS ESCALATED ENORMOUSLY. EVERYBODY THINKS ABOUT THE DEATHS, THE SENSELESS DEATHS OF YOUNG ADULTS. PEOPLE DON'T NECESSARILY THINK ABOUT THE BABIES WHO GENERALLY DON'T DIE BECAUSE THEY ARE DELIVERED IN A HOSPITAL SETTING WHERE NEONATOLOGIST IS THERE PREPARED TO GIVE NALOXONE TO COUNTERACT THE OPIOID. THIS IS AN ENORMOUS PROBLEM FOR NICUs, AND IT'S VERY EXPENSIVE, THOSE WORKING IN HOSPITALS KNOW THE COSTS ARE ENORMOUS BECAUSE THESE BABIES ARE TAKING UP SPECIAL CARE NURSERY OR NICU BEDS, BEDS NEEDED FOR EXTREMELY PREMATURE INFANTS OR INFANTS WHO NEED SURGERY. THIS IS AN AMAZING STATISTIC. IN 2015 ONE WISCONSIN COUNTY SPENT OVER A MILLION DOLLARS OUT OF $9 MILLION BUDGET ON CHILD WELFARE PLACEMENT LARGELY DUE TO PROVIDE EPIDEMIC. THE PROBLEM IS SOME OF THE WOMEN WHO ARE USING OPIOIDS DO NOT GET PRENATAL CARE AND THOSE WHO ARE ARE NOT ROUTINELY SCREENED FOR OPIOIDS. MANY TIMES THE OBSTETRICIAN DOESN'T KNOW THE WOMAN IS USING OPIOIDS AND THEY ARE NOT REQUIRED TO SCREEN THEM. WE WOULD RECOMMEND THAT THESE WOMEN SHOULD BE SCREENED BUT THAT IS NOT ROUTINE CARE YET. IF THE WOMAN DOES WANT TO BE TREATED, THE USUAL TREATMENT IS MEDICATION ASSISTED THERAPY, EITHER THROUGH METHADONE OR BUPRENORPHINE. THERE'S SOME DEBATE ABOUT WHICH ONE IS BETTER FOR THE MOTHER VERSUS THE BABY. THERE'S SOME INTEREST IN TRYING TO MEDICALLY SUPERVISE WITHDRAWAL BUT IT'S UNKNOWN RIGHT NOW WHETHER IT'S SAFE FOR THE PREGNANT WOMAN OR FETUS. SO RIGHT NOW WHAT'S BEING DONE IN PREGNANCY IS OFFERING PREGNANT WOMAN WHO DOES DISCLOSE THAT SHE'S ON OPIOID THIS CHOICE OF TREATMENT. BUT THEN THE BABIES ARE DIFFERENT FROM ADULTS. THEY ARE RESUSCITATED, AND THEN THE OTHER ISSUE IS SOME OF THEM, PARTICULARLY WITH METHADONE, DO NOT DEVELOP SYMPTOMS OF OPIOIDS, OPIOID WITHDRAWAL, RIGHT AWAY. SOMETIMES IT'S JUST AS THEY ARE ABOUT TO BE DISCHARGED THAT THESE SYMPTOMS DEVELOP. WHAT ARE THE SYMPTOMS? THEY ARE SWEATING, COULD BE SEIZING, CANNOT BE SOOTHED, THEY CLAW AT YOU, THEY CAN'T LATCH ON TO THE BOTTLE OR BREAST, THEY ARE VERY, VERY FRUSTRATED AND IT'S REALLY HEARTBREAKING TO SEE THEM. THE OTHER PROBLEM IS THERE'S NO CONSISTENT APPROACH TO CARE. SO YOU TALK TO ONE MOTHER-BABY UNIT IN OHIO, WHAT THEY ARE DOING IS WHAT WEST VIRGINIA IS DOING AND THAT'S DIFFERENT FROM WHAT THEY ARE DOING IN NEW HAMPSHIRE. AND NEONATES USE RESOURCES, AS I ALREADY MENTIONED, SO IT'S NOT JUST NICU BEDS, IT'S ALL THE SOCIAL SERVICES THAT ARE NEEDED. AND SO, WHAT WE'RE DOING RIGHT NOW IS NICHD HAS A PROJECT CALLED ACT NOW, ADVANCING CLINICAL CLINICAL TRIALS IN NEONATAL WITHDRAWAL IN PARTNERSHIP WITH ECHO PROJECT, ENVIRONMENTAL CHILD HEALTH OUTCOMES PROJECT, AND WE ARE USING OUR NEONATAL RESEARCH NETWORK IN PARTNERSHIP WITH THE IDeA STATES PEDIATRIC CLINICAL TRIALS NETWORK. SO THE NEONATAL RESEARCH NOW IS MAINLY IN URBAN SETTINGS, MATURE INVESTIGATORS, THEY HAVE BEEN WORKING TOGETHER FOR 30 YEARS, VERY EXPERIENCED IN CLINICAL TRIALS. THE IDeA STATES ARE FAIRLY NEW, THEY WERE ESTABLISHED A COUPLE YEARS AGO, MORE JUNIOR INVESTIGATORS. SO THE NEONATAL RESEARCH NETWORK IS MENTORING IDeA STATES PEDIATRIC CLINICAL TRIALS NETWORK, AND THE IDeA STATES HAVE THE HIGHEST PREVALENCE OF NOW. THEY ARE IN THE RURAL STATES, MOST AFFECTED BY THE EPIDEMIC. SO WE'RE VERY EXCITED ABOUT THAT. THEY ARE LOOKING AT THE VARIATION IN CLINICAL PRACTICE AND COMING UP WITH A COMPARATIVE EFFECTIVENESS CLINICAL TRIAL. THE EXCITING OPPORTUNITIES WILL BE TO TRULY INFLUENCE NATIONAL CARE BUT ALSO TO BE ABLE TO UNDERSTAND WHAT SOME OF THESE SYNTHETIC DRUGS ARE DOING TO THE DEVELOPING BRAIN. I MEAN, WE HAVE NO EXPERIENCE WITH A HUMAN DEVELOPING BRAIN BEING EXPOSED TO CARFENTANIL, AN ELEPHANT TRANQUILIZER. SO WE ARE VERY CONCERNED ABOUT THE LONG-TERM CONSEQUENCES OF EXPOSURE TO THESE DRUGS FOR THE BABIES. WELL, NOT THAT I WANT TO LEAVE YOU ON A SAD NOTE, THE FUTURE IS REALLY EXCITING. WE ARE ABOUT TO UNDERTAKE A STRATEGIC PLANNING PROCESS, NICHD'S LAST STRATEGIC PLAN WAS WRITTEN IN 2000. REMEMBER Y2K? THAT WAS A LONG TIME AGO. MANY OF YOU PARTICIPATED IN THE VISIONING PROCESS IN HELD IN 2012, AN OPPORTUNITY TO IDENTIFY GAPS ACROSS THE NIH. IT WAS NOT STRATEGIC PLAN FOR NICHD. AND WE HAVE A LOT OF CONCERNS, SCIENCE IS CHANGING, THERE ARE EMERGING EPIDEMICS SUCH AS OPIOIDS, SUCH AS ZIKA. WE NEED FLEXIBILITY. AND WE ALSO NEED TO BE ABLE TO ALIGN OUR RESOURCES WITH OUR AREAS OF FOCUS. SO THE END GOAL IS TO DETERMINE THE SCIENTIFIC PRIORITIES FOR NICHD MOVING FORWARD, AND TO ALIGN THESE RESOURCES WITH PRIORITIES. WE'RE MOVING ALONG. THIS IS SORT OF THE GOAL FOR 2018. WE'VE DEVELOPED A SET OF FOCUS QUESTIONS. WE HAVE A PLANNING SUBCOMMITTEE THAT MEETS MONTHLY, SOMETIMES TWICE MONTHLY. WHAT'S DIFFERENT IS WE HAVE -- THIS IS REALLY ONE OF THE BENEFITS OF BEING AT NIH, IS WE HAVE ALL OF THESE WAYS TO ANALYZE OUR PORTFOLIOS, AND THE IMPACT OF OUR PORTFOLIO. SO WE ARE LOOKING AT RELATIVE CITATION RATIOS, WE'RE LOOKING AT WHERE RESEARCH IS BEING CITED IN PATENT APPLICATIONS. WE'RE LOOKING AT PROFESSIONAL SOCIETY GUIDELINES TO SEE WHERE SOME OF THE CLINICAL RESEARCH IS BEING CITED AND HOW IT'S CHANGING PRACTICE. WE'RE LOOKING AT THE ANALYSIS OF THE REVIEW GROUP OUTCOMES. SO LOOKING AT THE STUDY SECTIONS THAT HAVE AT LEAST 10% OF THEIR APPLICATIONS THAT GET ASSIGNED WE'RE USING DIFFERENT METRICS. WE FEEL OUR MISSION IS SO BROAD THAT ONE METRIC MIGHT NOT EQUALLY APPLY TO A BASIC SCIENCE BRANCH, AS OPPOSED TO A MORE CLINICAL BRANCH. WE ALSO ARE INCLUDE BOTH INTERNAL STAFF AND EXTERNAL COMMUNITY. WHEN THE STRATEGIC PLAN WAS DONE IN 2000 THERE WAS NO ONE FROM NICHD INVOLVED IN THE PROCESS. WE REALLY WERE GOING TO HAVE IT HALF AND HALF. AND BECAUSE WE HAVE A BROAD MISSION THAT INCLUDES CHILD HEALTH, WOMEN'S HEALTH, REPRODUCTIVE HEALTH, INTELLECTUAL DISABILITIES, CHILD DEVELOPMENT, WE ALSO HAVE THE NATIONAL CENTER FOR MEDICAL REHABILITATION RESEARCH, WHICH IS ADULTS AS WELL AS CHILDREN, WE HAVE TO COVER ALL THOSE THINGS. DESPITE THAT, WE HOPE TO COMPLETE IT IN THIS CALENDAR YEAR, BECAUSE THERE'S SOME PRESSING ISSUES. AND WE HAVE A REFRESHED WEBSITE IF ANYBODY WANTS TO GO TO THE NICHD WEBSITE, WE WILL HAVE A TARGETED SPACE FOR THESE ANALYSES, AS WELL AS UPDATES ON THE PROGRESS OF THE PLAN. SO WITH THAT, I'M GOING TO SUMMARIZE AND HOPEFULLY WE HAVE TIME FOR QUESTIONS. THREE BULLETS. SO I HOPE I'VE LEFT YOU WITH THE MESSAGE THAT INCLUSION OF PREGNANT AND LACTATING WOMEN IN CLINICAL RESEARCH IS NEEDED. YOU CAN ALL BE AMBASSADORS AND HELP US WITH THE CHALLENGE. WE'VE MADE SOME PROGRESS IN THE PAST YEAR. WE HAVE THESE NEW RCDC CODES. WE WILL HAVE VERY SOON -- WE HAVE TO GET THE REPORT TO THE HHS SECRETARY BY SEPTEMBER OF THIS YEAR. IT WILL ALSO GO TO CONGRESS. SO WE WILL HAVE SOME CONCRETE RECOMMENDATIONS AND CONGRESSWOMAN JAMIE HERRERA BUTLER FROM THE STATE OF WASHINGTON WAS VERY PLEASED WITH THE PROGRESS OF THE TASK FORCE FROM WHAT SHE'S HEARD AND SHE WANTED TO KNOW IF WE'RE GOING TO CONTINUE I THAT'S ALWAYS GOOD TO HEAR FROM A MEMBER OF CONGRESS, THIS IS ON HER RADAR SCREEN. THINK GOOD THOUGHTS FOR THE CLINICAL CENTER WORKING GROUP DISCUSSION THAT WE'LL BE ABLE TO HAVE PREGNANT WOMEN ENROLLED IN PROTOCOLS. WE'RE INCLUDING PARTICIPANTS IN MOST OF THE THINGS WE DO PUBLICLY SO WE CAN PUT A HUMAN FACE ON THE NEED FOR RESEARCH SPECIFICALLY FOR OUR UNDERREPRESENTED POPULATIONS. OPIOID USE IN TERMS OF SCREENING AND TREATMENT IS A MAJOR ISSUE. I DON'T NEED TO TELL YOU THAT. BUT IT IS CERTAINLY A BIG ISSUE FOR WOMEN AND CHILDREN AND YOU DON'T NECESSARILY HEAR THAT ANGLE OF IT ON THE NEWS. SO WE ARE HOPING TO GET FUNDING FROM THE OFFICE OF THE DIRECTOR TO CONTINUE THAT WORK, AND WE CERTAINLY SEE A VERY STRONG PARTNERSHIP MOVING AHEAD WITH THE OFFICE FOR RESEARCH AND WOMEN'S HEALTH, AND OUR STRATEGIC PLANNING PROCESS WILL ALLOW US AN OPPORTUNITY TO FORMALIZE THAT. HOPEFULLY I HAVE TIME FOR QUESTIONS. I WANT TO THANK YOU FOR YOUR ATTENTION. [APPLAUSE] >> THANK YOU SO MUCH, DR. BIANCHI. THE FLOOR IS OPEN FOR QUESTIONS. DR. WOOD, PALER AND LANGER. >> THANKS SO MUCH. A LOT OF INTERESTING STUFF. I HAVE PROBABLY MORE COMMENT THAN I SHOULD TAKE UP PEOPLE'S TIME FOR BUT THE FIRST ONE I DID WANT TO MENTION IN RESPONSE AS A COMMENT TO THE ISSUES THAT SURROUND OPIOID USE AND ADDICTION BY PREGNANT WOMEN, ONE OF THE KEY ISSUES EVERYONE NEEDS TO KEEP IN MIND, TWO THINGS. ONE IS THE REASON A LOT OF WOMEN, SCREENING ISSUE GETS REALLY DICEY. SOUNDS EASY BUT WHEN SCREENING IN MANY STATES LEADS TO THE WOMAN'S CHILDREN BEING AUTOMATICALLY TAKEN AWAY, THAT'S AN ISSUE. WHEN THAT SCREENING AND WHOSE KIDS GET TAKEN AWAY, IF YOU LOOK AT RACE AND ETHNICITY AND CLASS ISSUES THAT COME UP, IT'S REAL. SO THAT FEAR OF CRIMINALIZATION AND TREATING OF PREGNANT WOMEN AS CRIMINALS AS OPPOSED TO TREATING IT AS I THINK ALL THOSE IN THIS ROOM WOULD SAY, IT'S A HEALTH ISSUE, WE SHOULD TREAT IT AS A HEALTH ISSUE, GIVE THEM THE BEST CARE POSSIBLE, UNFORTUNATELY THAT'S NOT THE REALITY OF HOW IT PLAYS OUT ON TELEVISION OR IF WE HIGHLIGHT IT AS, OH, THESE BAD WOMEN, YOU KNOW, WE NEED TO MAKE THEM DO SOMETHING. I THINK WE NEED TO BE VERY CAREFUL ABOUT THAT. AND IT'S BEEN NICHD'S FUNDED RESEARCH THAT HAS REALLY SHOWN, FOR EXAMPLE, THAT MANY OF THE MISTAKES MADE WITH THE CRACK COCAINE EPIDEMIC WHERE WE EXPECTED A GENERATION OF CRACK BABIES, WHEN IN FACT IT WAS DATA SUPPORTED AND RESEARCH SUPPORTED BY NICHD THAT SHOWED IT WAS POVERTY. IT REALLY WASN'T DRUG EXPOSURE IN UTERO THAT HAD THE EFFECTS ON CHILDREN BUT THE ASSOCIATION AND THE CAUSATIVE ACTION WAS POVERTY. AND SO WE AGAIN NEED TO BE VERY CAREFUL ABOUT HOW WE TALK ABOUT THESE THINGS BECAUSE DATA WILL SHOW US WHAT IS AND WHAT ISN'T, AND WE NEED TO OBVIOUSLY CONTINUE THAT RESEARCH. BUT I WOULD JUST BE CAREFUL ABOUT THAT. THE OTHER QUESTION, WHICH GOES BACK TO YOUR FIRST PART OF YOUR TALK, WHICH WAS ABOUT INCLUSION OF PREGNANT WOMEN, MUCH OF THE RESEARCH WAS ON HEALTHY PREGNANT WOMEN, SEEMED TO BE ABOUT PREGNANCY. ALL OF WHICH IS DEEPLY UNDERSTUDIED. BUT IS THIS ALSO ABOUT, YOU KNOW, AN AIDS TRIAL, HIV TRIAL, WHERE WE'RE TALKING ABOUT PREGNANT WOMEN WHO COULD -- WHO NEED TO BE STUDIED AS PATIENTS, AT THE CLINICAL CENTER, AND SO ON. >> LET ME FIRST OF ALL THANK YOU FOR YOUR FIRST POINT. I SHOULD HAVE BEEN MORE EXPLICIT WHEN I TALKED ABOUT THE MONEY THAT'S BEING SPENT ON SOCIAL SERVICES. IT'S BECAUSE THE BABIES ARE TAKEN AWAY FROM THEIR MOTHERS AND YOU'RE ABSOLUTELY RIGHT THAT'S PART OF THE ISSUE WHICH HAS TO BE SOLVED, BUT WE DECRIMINALIZE THE DISCLOSURE OR THE RANDOM FINDING OF THE FACT THAT THE MOTHER HAS TAKEN OPIOIDS. SO THAT'S A HUGE ISSUE. AND YOU'RE ABSOLUTELY RIGHT. THE SECOND ISSUE REALLY, IT IS PARTLY ABOUT STUDYING PREGNANT WOMEN AND HOW PREGNANCY AFFECTS THEIR METABOLISM OR, YOU KNOW, HOW THEY PROCESS DRUGS. BUT YOU'RE RIGHT, IT'S ABOUT A BIGGER ISSUE, LIKE IT IS TRUE THAT IF YOU ARE PREGNANT AND YOU ARE ENROLLED IN AN NCI PROTOCOL AND NEED TREATMENT, YOU CAN BE TREATED. BUT THAT'S CURRENTLY BEING DONE AT WALTER REED, FOR EXAMPLE. BUT I THINK WE'RE TALKING ABOUT EVERYTHING, NOT JUST PREGNANCY STUDIES PER SE. IT'S, AGAIN, INCLUDING PREGNANCY AS A REPRESENTED POPULATION AND NOT AUTOMATICALLY EXCLUDING THE POPULATION AS A VULNERABLE POPULATION. >> THANK YOU VERY MUCH FOR BRINGING UP SUCH AN IMPORTANT SUBJECT. SO MANY STUDIES TO BE DONE. ONE AREA THAT AS A PHYSICIAN I WORRY ABOUT IS PAUCITY OF MEDICATIONS THAT WE CAN GIVE TO PREGNANT WOMEN. AND I HAPPEN TO BE A PEDIATRICIAN, I APPLAUD THAT THE FDA IS MANDATING MORE TRIALS GOING TO CHILDREN BUT I THINK THAT WE HAVE A LONG WAY TO GO WITH PREGNANT WOMEN AND THE CONCEPT OF LACTATING. BUT THERE'S ALSO THE CONCERN ABOUT THE FACT THAT THERE ARE RISKS, AND THERE ARE TRUE RISKS TO UNBORN CHILDREN, SOMETIMES GIVING MEDICATION WE DON'T KNOW. ANIMAL STUDIES DON'T ALWAYS TELL 100%. HOW ARE WE NAVIGATING THAT FINE LINE OF MAKING DECISIONS, WE NEED TO BRING MORE OF THESE, SO THAT PHYSICIANS ARE NOT FREAKED OUT AND NOT GIVING THE DRUGS THAT NEED TO BE GIVEN TO WOMEN BECAUSE THEY ARE WORRIED DOWN THE LINE ABOUT SOMETHING HAPPENING AND THE POTENTIAL SUITS AND OF COURSE THE CONCERN ABOUT THE BABY. SO JUST IF YOU COULD COMMENT A LITTLE BIT ON HOW WE CAN GET MORE DRUGS TESTED AND YET NOT FACE SOME REAL RISKS WITH DOING THAT. >> YEAH, I THINK THAT'S AN EXCELLENT QUESTION. AND WE DO HAVE A MECHANISM WITHIN NICHD, THERE'S AN OBSTETRIC AND PEDIATRIC CLINICAL TRIALS NETWORK LOOKING SPECIFICALLY AT PHARMACOLOGY. JUST TO GIVE AN EXAMPLE, PRAVASTATIN, A CHOLESTEROL LOWERING DRUG IS BEING EXAMINED AS POSSIBLE MEDICATION FOR PRE-ECLAMPSIA, CATEGORY X MEDICATION NEVER DESIGNED AS PREVENTIVE STRATEGY FOR PRE-ECLAMPSIA BUT THROUGH THE PHARMACOLOGY NETWORK WE'RE ABLE TO DO SMALL SAFETY AND EFFICACY STUDIES SO 10 AND 10, FOR EXAMPLE, AND THEN SHOWING THAT IF IT'S SAFE IN THAT CIRCUMSTANCE AND ACTUALLY TAKING A POPULATION OF PREGNANT WOMEN AT HIGH RISK FOR WHATEVER, BUT IN THIS STUDY PRE-ECLAMPSIA AND PREVENTED PRE-ECLAMPSIA IN THE WOMEN WHO TOOK THE DRUG, THEN WE CAN MOVE TO A LARGER TRIAL USING THE MATERNAL FETAL MEDICINE, LOOKING AT SMALL SCALE AND TEST LARGE SCALE. BUT -- YOU KNOW, THE BPCA, IT'S ANOTHER ISSUE. WE ARE ALSO THE LEAD INSTITUTE FOR STUDYING PEDIATRIC MEDICATIONS AS WELL. >> YES, THANK YOU SO MUCH FOR A GREAT PRESENTATION AND FOR THE STRONGER FOCUS ON MATERNAL HEALTH. DURING PREVIOUS SECTION OF THE MEETING WE WERE TALKING ABOUT HIGH RATES OF MATERNAL MORTALITY AND RACIAL DISPARITIES IN THIS COUNTRY, IN PARTICULAR UNDERLYING CAUSES THAT COULD EXPLAIN RACIAL DISPARITIES. I WAS INTERESTED IN HEARING FROM YOU HOW THAT TOPIC WOULD FIT INTO YOUR AGENDA AND YOUR STRATEGIC PLAN. >> YEAH, I WAS ASKED THAT AT CONGRESS LAST WEEK AS WELL. IT'S ON THEIR RADAR SCREEN. WE'RE NOT STUDYING MATERNAL MORTALITY, PER SE. WE'RE STUDYING THESE UNDERLYING PREDISPOSING CONDITIONS. LIKE DIABETES. LIKE PRE-ECLAMPSIA, LIKE POSTPARTUM DEPRESSION, INFECTION. SO THE TOPICS COME UP, BUT AS SPECIFIC DISEASES OR DISEASE RISK FACTORS WHERE WE'RE GENERALLY EITHER TESTING UNDERLYING MECHANISMS IN MORE BASIC SCIENCE SETTINGS OR WE'RE ACTUALLY DOING CLINICAL TRIALS. SO, WE DID, FOR EXAMPLE, ONE STUDY OF CESAREAN SECTIONS, WOMEN WHO HAD UNDERGONE CESAREAN SECTION, A THIRD OF THE POPULATION, ADDING ZITHROMAX BECAUSE INFECTIONS ARE HIGH AND CAN BECOME SERIOUS, LIKE THE PREVASTATIN OR ZITHROMAX, BUT IT ALSO ALL RELATED TO POVERTY, DISPARITY IN CARE, THERE'S A SHOCKING DESERT OF MATERNAL CARE RIGHT HERE IN WASHINGTON, D.C. I MEAN, I WAS ASTONISHED TO FIND OUT THAT THE WHOLE EASTERN PART OF THE CITY, THERE'S REALLY NO MATERNAL FETAL MEDICINE EXPERTISE THAT WOMEN WHO ARE HIGH RISK NEED TO TRAVEL ON PUBLIC TRANSPORTATION FOR VERY LONG PERIODS OF TIME JUST TO SEE A DOCTOR IN WASHINGTON, D.C. SO IT'S A SERIOUS ISSUE. AND IT WILL BE IN OUR STRATEGIC PLAN. >> ONE COMMENT THEN CARMEN, THEN KIM AND CONNIE. DR. BIANCHI, YOU'VE TALKED ABOUT CLINICAL TRIALS QUITE A BIT. WE HAVE AN AUDIENCE THAT INCLUDES THE PUBLIC HERE. SO CAN YOU DRAW THE DISTINCTION BETWEEN CLINICAL RESEARCH STUDIES AND CLINICAL TRIALS? AND HOW THERE'S AN INCREDIBLE NEED FOR CLINICAL RESEARCH INVOLVING PREGNANT WOMEN AND PREGNANCY AND DISEASE, AND I DON'T REMEMBER WHO THE PERSON THAT SAID THIS WAS, IT WAS A COUPLE YEARS AGO, AND IT REALLY MADE IT CLEAR FOR ME, PREGNANT WOMEN GET SICK, AND SICK WOMEN BECOME PREGNANT, THAT DISTILLS THE ISSUES. MAYBE THE DISTINCTION BEFORE THE OTHER QUESTIONS. YOU PRESENTED NICHD DATA AND RANDOMIZED CONTROL TRIAL DATA WITH POPULATION PIECE, I DON'T KNOW IF CLINICAL RESEARCH WAS INCLUDED IN YOUR POPULATION COLUMN IN THAT SLIDE. >> OH, THAT I DON'T KNOW OFFHAND. BUT, YOU KNOW, WE DO MORE THAN CLINICAL RESEARCH AND CLINICAL TRIALS BECAUSE WE FUND QUITE A LOT OF BASIC SCIENCE RESEARCH. AND WE'RE CERTAINLY LOOKING AT SEX AS A BIOLOGICAL VARIABLE. AND WE'RE LOOKING AT TRANSLATIONAL RESEARCH. BUT CLINICAL TRIALS, IT'S AN EVOLVING DEFINITION RIGHT NOW AT NIH. SO IT'S KIND OF A LITTLE FUZZY, BUT USUALLY WITH CLINICAL TRIALS YOU ARE EVALUATING A SPECIFIC CHANGE, OR A SPECIFIC PERTURBATION, WHETHER IT'S GIVING A MEDICATION OR DOING EXERCISE OR FILLING OUT A QUIZ, THERE'S BEEN A LOT OF DISCUSSION ABOUT PSYCHOLOGICAL TESTING THAT THAT IS NOW CONSIDERED TO BE A CLINICAL TRIAL. WHEREAS CLINICAL RESEARCH IS PROBABLY A BROADER SPECTRUM, NOT NECESSARILY EVALUATING A SPECIFIC INTERVENTION, VERSUS A NON-INTERVENTION. >> THANK YOU. WE NEED BOTH IN RELATED TO PREGNANCY. DR. GREEN, DR. GREGORY AND DR. WEAVER AND WE ARE GOING TO HAVE TO KEEP THOSE QUICK BECAUSE WE'RE OVER TIME, IN RESPECT FOR DR. BIANCHI'S TIME TOO. >> OKAY, GREAT. A COUPLE THINGS. CONGRATULATIONS ON PUTTING TOGETHER A PROGRESSIVE AGENDA. I WANT TO MAKE A COUPLE COMMENTS FOR YOUR CONSIDERATION. THE FIRST ONE IS, THERE ARE -- NOT EVERY WOMAN WHO IS ON OPIOIDS IS ADDICTED TO OPIOIDS. I JUST WANT TO MAKE CERTAIN THAT WE ARE CLEAR ON THAT. THERE ARE WOMEN WHO HAVE A LEGITIMATE REASON TO BE ON OPIOIDS AND NOTHING ELSE WORKS. WE'VE NOT CREATED THE ALTERNATIVE MEDICATIONS, NOT IN THE PIPELINE, TO PROVIDE GOOD QUALITY CARE FOR WOMEN, AS WELL AS FOR MEN. SO, SOME OF THOSE WOMEN ACTUALLY, SURPRISE, SURPRISE, THEY GET PREGNANT. AND IF YOU TAKE AWAY THEIR OPIOIDS, YOU ACTUALLY MAY POTENTIALLY BE CREATING A VERY STRESSFUL ENVIRONMENT FOR THE MOTHER AS WELL. DESPITE FACT WE KNOW THERE ARE CHALLENGES FOR THE CHILD. I JUST WANT TO MAKE CERTAIN THAT WE'RE VERY CLEAR ON THAT, AND I JUST DON'T THINK THAT A POINT HAS BEEN MADE OFTEN ENOUGH DURING THIS MEETING. SO I THINK WE NEED TO TAKE A LOOK AT THOSE PARTICULAR ISSUES. THE OTHER THING I WOULD SAY, ENCOURAGE YOU TO DO, IS THERE ARE CHILDREN WHO ARE ON OPIOIDS. FOR INSTANCE, SOME CHILDREN WITH CANCER, THEY ARE ON IT FOR A LONG PERIOD OF TIME. AND SO THERE'S AN OPPORTUNITY TO REALLY LOOK AT THOSE CHILDREN. AND THEN I THINK THE OTHER POINTS THAT I WOULD MAKE IS THE DISPARITIES ISSUE. AND I DIDN'T HEAR A LOT COME OUT. I KNOW THAT WASN'T -- THERE ARE SOME WOMEN WHO MAY BE LACTATING, OR CAN LACTATE, OR DON'T HAVE ACCESS TO CARE, AND WHAT THOSE DIFFERENCES MIGHT BE. SO I JUST REALLY WOULD ENCOURAGE US TO SORT OF THINK ABOUT THOSE IN MORE OF A GLOBAL PERSPECTIVE. MORE OF A COMMENT. >> AGAIN, I THINK CONDENSING BECAUSE OF TIME, BUT $500 MILLION WAS GIVEN TO NIH, MAINLY TO NINDS, AND NIDA FOR OPIOID-RELATED RESEARCH IN THIS FISCAL YEAR. NOW, IF YOU'VE READ DR. COLLINS AND DR. VOLKOW'S PIECE IN THE NEW ENGLAND JOURNAL OF MEDICINE THERE'S A MAJOR EFFORT TO DEVELOP NEW NON-ADDICTIVE PAIN MEDICATIONS. BUT WE ARE ALL -- ALL THE INSTITUTES ARE WORKING ON DIFFERENT WAYS TO SPEND THAT $500 MILLION, EVEN THOUGH IT WAS OFFICIALLY GIVEN TO THOSE INSTITUTES, THE DIRECTOR OF NIH HAS THE AUTHORITY TO REDISTRIBUTE THE MONEY. SO THERE'S BEEN AN ONGOING PROCESS OVER THE LAST FEW MONTHS WHERE EACH INSTITUTE PUT FORWARD PROPOSALS, AND WE FOCUSED ON THE NEONATES BECAUSE THEY WERE NOT GETTING ANY ATTENTION AT ALL. THERE'S SOME SPECIFIC DIFFERENCES WHICH I TRIED TO COMMUNICATE BUT OUR OTHER PROPOSAL THAT WE WANTED TO BE THE LEAD ON WAS ON PAIN IN WOMEN OF REPRODUCTIVE AGE. SO IT'S EXACTLY GETTING AT WHAT YOU MENTIONED. I DIDN'T TALK ABOUT IT BECAUSE WE DON'T KNOW YET WHAT THE STATUS OF THAT PROPOSAL IS. BUT WE KNOW THAT FOR A VARIETY OF REASONS, YOU KNOW, WOMEN WHO HAVE VERY LEGITIMATE NEED FOR PAIN MEDICATION GET STARTED IN REPRODUCTIVE WINDOW AND WHEN THEY GET PREGNANT THEY NEED THOSE MEDICATIONS. WE WANT TO STUDY THE REASONS THEY ARE ON THE MEDICINES AND WHAT WE CAN DO ABOUT IT TO HELP THEM STAY PAIN FREE AS WELL AS HAVE A HEALTHY PREGNANCY AND HEALTHY BABY. AND DISPARITIES, SO DISPARITIES ARE WITHIN EVERYTHING THAT WE DO. PROBABLY SINCE YOU AND I WERE ON COUNCIL WE HAVE A NEW OFFICE OF HEALTH EQUITY, AND CHARISSE LAMAR IS THE RELATIVELY NEW DIRECTOR THERE. SO SHE'S INVOLVED IN ALL THESE ACTIVITIES, AND IT'S VERY MUCH A PART OF OUR THINKING. >> THIS IS PROBABLY JUST AN EXTENSION OF THE QUESTION, YOU MADE MENTION OF THE LIFE COURSE, SO PEOPLE ASSUME THAT INCLUDES SOCIAL DETERMINANTS. BUT I'M HOPING IN THE STRATEGIC PLAN THAT THAT IS SOMETHING THAT NICHD STARTS TO FUND, AND EXPLICITLY WANT TO PUT IN A PLUG FOR HEALTH SERVICES RESEARCH AND COMMUNITY-BASED PARTICIPATORY RESEARCH COMING FROM NICHD. >> OKAY. NOTED. THANK YOU. >> SO, I WAS WONDERING IF YOU HAD ANY IDEAS FOR HOW WE CHANGE THE CULTURE LIKE THE HOSPITAL THAT YOU WERE DESCRIBING. I AM HOST OF A CONVERSATION WITH LOCAL HOSPITAL ADMINISTRATORS FOR OUR CTSI TO TRY TO EXPAND PARTICIPATION IN COLLABORATION IN RESEARCH, ESPECIALLY TRIALS, AND LOCAL ADMINISTRATORS SAID WE WON'T ALLOW ANY FEMALE SUBJECTS OF REPRODUCTIVE AGE, EVEN IF THEY ARE NOT PREGNANT, BECAUSE THEY SAID -- THEY COULD GET PREGNANT LATER AND BLAME THE TRIAL. SO FOR LIABILITY REASONS THEY JUST WOULDN'T DO IT. WHERE DO YOU -- HOW DO YOU -- >> YES, STACY WAS TELLING ME ABOUT HER SUCCESS ON THREE IRBs TRYING TO CHANGE THE CULTURE AT UNIVERSITY OF CHICAGO -- UNIVERSAL OF ILLINOIS, CHICAGO. >> I DID A TRAINING FOR ALL THE IRBs. I SAID YOU CANNOT SAY VULNERABLE POPULATIONS ARE ALL CREATED EQUAL, RIGHT? A PERSON IN PRISON AND PREGNANT WOMAN WITH NOT THE SAME CREATURES. WE DID RETRAINING, LITERALLY. >> BUT ADMINISTRATOR SAYS WE'RE NOT ACCEPTING THAT LIABILITY. >> CTSI. >> NO, THE CTSI WAS TRYING TO ENGAGE LOCAL HOSPITALS TO THINK ABOUT RESEARCH AND PARTNER AND HOSPITAL ADMINISTRATORS SAY WE'RE NOT ACCEPTING THE LIABILITY OF ANY. >> WOMEN OF REPRODUCTIVE AGE. >> THAT'S DISTURBING. >> YEAH, VERY. >> I KNOW THAT DR. BIANCHI AND I BOTH CARE ABOUT THOSE ISSUES AND I WOULD LET YOU ALL -- LET US TAKE THAT UP TO HAVE SOME DISCUSSION INTERNALLY, CLEARLY NIH HAS LIMITS IN TERMS OF SCOPE BUT ORWH DID LEAD A MEETING ON INCLUSION OF PREGNANCY-INDUCED AND CLINICAL RESEARCH FIVE YEARS AGO AND PUT FORWARD ACTUALLY A CALL FOR A SPECIFIC RESEARCH AGENDA, RELATED TO PREGNANT WOMEN, AND THESE ISSUES WERE THERE, ETHICAL ISSUES, IRB ISSUES, LIABILITY, MEDICAL LIABILITY ISSUES, FDA ISSUES. AND SO I'M GOING TO SHARE THAT WITH YOU, DR. BIANCHI, AND WE'LL REVIEW THAT INTERNALLY AND I'LL SEND IT OUT TO ADVISORY COMMITTEE. I THINK MANY OF THE ISSUES ARE STILL SALIENT AND RELEVANT. >> YEAH, UNFORTUNATELY. >> DO PRIVATE FUNDERS GET TO IGNORE IT, OR ARE YOU TRYING TO ENGAGE? BECAUSE THAT'S THE SITUATION. THEY GET THE EXCUSE OF -- >> I THINK YOU PUT A VERY IMPORTANT ISSUE ON THE TABLE. I APPRECIATE THAT, DR. WEAVER, BECAUSE IT IS SO CHALLENGING TO FUND RESEARCH RELATED TO PREGNANT WOMEN, AS YOU SAW WITH PREGSOURCE. HAVE YOU TO BE CREATIVE. WE HAVE TO WORK MORE IN PARTNERSHIPS. IF THE PARTNERS WITH COMING AT THIS WITH DIFFERENT VIEWPOINTS, THAT'S GOING TO REALLY INHIBIT OUR ABILITY TO PARTNER EFFECTIVELY. SO WE NEED TO FIND A WAY THAT WE CAN FIND SOME COMMON GROUND LIKE WHAT IS SOMETHING WE COULD ALL PARTICIPATE IN. SO PLEASE JOIN ME IN THANKING DR. BIANCHI FOR THIS PRESENTATION. [APPLAUSE] I KNEW PEOPLE WOULD BE SO INTERESTED, SO DELIGHTED TO HAVE YOU HERE AT NIH AS WELL. WE FEATURED YOUR PHOTOS WHEN YOU FIRST BECAME I.C. DIRECTOR,& WE'RE DELIGHTED TO HAVE YOU VISIT WITH US AND LOOK FORWARD TO YOU COMING AGAIN. AND SO THANK YOU SO MUCH FOR JOINING US. WE APOLOGIZE FOR GOING OVER TIME. SO WE ARE ACTUALLY AT OUR TIME. TWO MINUTES OVER THE TIME TO CONCLUDE OUR MEETING. AND I FEEL REALLY BADLY THAT WE DID NOT HAVE A LOT OF TIME FOR DISCUSSION. IF YOU ALL ARE WILLING TO STAY FOR FIVE MINUTES, WE COULD HAVE A LIMITED DISCUSSION. YOU KNOW, YOU ALL KNOW HOW TO GET IN TOUCH WITH ME AS WELL. BUT WHY DON'T WE SEE IF THERE ARE ANY PRESSING HOT BUTTON ISSUES THAT ANYONE WANTS TO MAKE JUST TO HAVE ON THE LIST OF HOT BUTTON ISSUES THAT WE CAN CONSIDER FOLLOW-UP IN THE FUTURE. DR. HELLER? RACHEL? I'M SORRY. GO AHEAD. >> WE DIDN'T HAVE TIME, OF COURSE WITH ALL THE PRESSING ISSUES, TO DISCUSS A MAJOR RECRUITING TOOL FOR MANY OF US DOING CLINICAL TRIALS. AND ENGAGING COMMUNITIES AND RESEARCHERS ADVERTISING ON FACEBOOK. THERE HAVE BEEN SERIOUS ISSUES, AS MOST PEOPLE IN THE ROOM KNOW, WITH FACEBOOK ADVERTISING, AND I'M NOT TALKING ABOUT RUSSIAN INFLUENCE. I'M TALKING ABOUT ALL SORTS OF THINGS ABOUT SECURING CONFIDENTIALITY FOR PARTICIPANTS IN RESEARCH. MYSELF AND MY TEAM HAVE DONE A GREAT DEAL OF WORK IN THIS AND PUBLISHED ON THIS, BUT THE GROUND IS CHANGING. I WOULD REQUEST THAT WE HAVE SOME CONSIDERATION AS TO HOW DO UTILIZE SOCIAL MEDIA, WHICH IS SUCH AN IMPORTANT POWERFUL TOOL, TO ACCESS POPULATIONS THAT ARE SO DIFFICULT TO REACH UNDER OTHER CIRCUMSTANCES. WE RECRUITED 800 PREDOMINANTLY BLACK WOMEN INTO AN HIV PREVENTION CLINICAL TRIAL ON USING FACEBOOK PRIMARILY. I JUST WANT TO PUT THAT ON THE TABLE. THE RISKS AND THE BENEFITS OF SOCIAL MEDIA IN INCLUDING AT-RISK POPULATIONS IN HEALTH PROMOTION AND IN CLINICAL RESEARCH. >> THANK YOU, DR. JONES. OTHER-- I'M SCANNING THE ROOM FOR HOT BUTTON ISSUES. OH, I'M SORRY. YOU HAVE TO PUT YOUR HAND UP HIGHER. >> YEAH, I NEED TO LEARN TO DO THAT. THIS MAY NOT BE A HOT BUTTON ISSUE, AND I'M SURE YOU WILL AGREE WITH ME, BUT I'M ALL IN FAVOR OF USING THE HEALTH OF WOMEN INSTEAD OF WOMEN'S HEALTH, BUT I WOULD ENCOURAGE YOU TO IN THE NARRATIVE MAKE VERY, VERY CLEAR WE SHOULDN'T FORGET ABOUT REPRODUCTIVE HEALTH. I DON'T MEAN ONLY MATERNAL HEALTH, I MEAN CONTRACEPTION, YEAH, I DON'T KNOW ABOUT ABORTION, WHAT ROLE IT WOULD HAVE IN THE AGENDA BUT STILL IT'S AN IMPORTANT ISSUE. >> THANK YOU VERY MUCH FOR THAT. DR. PAIGE, HOT TOPIC OR QUESTION? >> SORT OF IN THE CONTEXT OF THE TRANS-NIH STRATEGIC PLAN, AND THINKING ABOUT THE -- JUST THINKING ABOUT THE -- WHAT I SEE AS A KIND OF COLLISION THAT IS COMING, SORT OF COMING AT THIS, AT THIS OFFICE, AT SOME POINT. AND FOR THIS COMMITTEE. AND THAT IS SEX AS A BIOLOGICAL VARIABLE IS SOMETHING THAT OF COURSE IS AND SHOULD BE PUSHED ACROSS ALL OF NIH, AND IT WILL BE OF NECESSITY BRING A COLLISION WITH THE WOMEN'S HEALTH, HISTORICALLY FRAMED -- THE CONTEXT OF WOMEN'S HEALTH HISTORICALLY FRAMED. SO THAT THE QUESTION IS, WILL WE AT SOME POINT TAKE ON STRATEGICALLY THE QUESTION OF ROLLING OUT SEX AS A BIOLOGICAL VARIABLE AS AN INPUT FOR THINKING NOT JUST ABOUT THE HEALTH OF WOMEN BUT -- AND THE HEALTH OF GIRLS, BUT THE HEALTH OF MEN AND THE HEALTH OF BOYS. AND WON'T THAT ACTUALLY BE A MUCH RICHER AND FORWARD-LOOKING AGENDA THAT I WOULD LOVE TO SEE US AS A COMMITTEE TAKE ON AT SOME POINT IN THE FUTURE. >> THANK YOU, DAVID. DR. GREEN, I'M GOING TO GIVE YOU THE LAST WORD. WERE YOU TRYING TO MAKE A COMMENT? DR. GREEN AND THEN DR. GREGORY AND WE'LL ADJOURN. >> SO THIS IS JUST HOT TOPIC. WE'VE TOUCHED ON IT. IN REGARDS TO WOMEN COMING THROUGH -- RECEIVING THE MAJOR AWARDS, I WANT TO RECOMMEND THAT ACTUALLY THAT'S MORE OF A LARGER DISCUSSION. AND I WOULD SPECIFICALLY LIKE US TO LOOK AT THE STATUS OF WOMEN OF COLOR IN THAT CONVERSATION. CONSIDERING AGAINST THE REPORT THEY MAY BE PARTICULARLY AT RISK. I'M NOT JUST TALKING ABOUT PIONEER AWARDS, I'M TALKING ABOUT OTHER AWARDS. I WON'T BE HERE FOR THAT BUT IT NEEDS TO OCCUR. >> THANK YOU. >> THANK YOU, DR. GREEN. DR. GREGORY. >> I WOULD LIKE TO COMMEND YOU FOR DOING MORE WITH LESS, GIVING OUT ALL THIS EXTRA MONEY. SOMEHOW THERE NEEDS TO BE AN ATTEMPT, I WANT TO GO ON THE RECORD SAYING THE OFFICE SHOULD BE GETTING MORE. >> THANK YOU, DR. GREGORY. I THINK WE'LL END ON THAT NOTE. THANK YOU TO THE ADVISORY COMMITTEE MEMBERS, AND THANK YOU TO TEAM ORWH AS WELL AS THE CCRWH MEMBERS WHO ARE HERE AND OUR CONTRACT SUPPORT AS WELL FROM CAMPBELL AND COMPANY. THANK YOU, EVERYBODY. WE ARE ADJOURNED. [APPLAUSE] [END OF PROGRAM]