GREAT TO SEE EVERYBODY HERE. JUST WANT TO LET YOU KNOW NANCY DAVIDSON IS NOT ABLE TO BE WITH US TODAY SO WE HAVE ASKED PAT LOEHRER TO BE CHAIR THIS MORNING WHICH SHE HAPPILY AGREED TO DO. NANCY IS NOT LEAVING SHE'S JOINING THE BOARD OF SCIENTIFIC COUNSELORS FOR THE INTRAMURAL PROGRAM AND IS GOING TO BE BSC REPRESENTATIVE TO CTAC. WE HOPE TO SEE HER VERY SOON. WE ARE IN THE PROCESS OF GOING THROUGH THE APPOINTMENTS PROCESS FOR ADDITIONAL MEMBERS TO CTAC. >> IT'S SHOW TIME HERE. I'M TRYING TO BE FILL IN NICE FOR NANCY HERE. SO WELCOME, THIS IS THE 37th CTAC MEETING. FOR THOSE OF YOU WHO DON'T KNOW EACH OTHER I WOULD AT THE BREAK PLEASE SHAKE HANDS AND GET TO KNOW EACH OTHER. I HAVE A COUPLE OF OPENING STATEMENTS I'M REQUIRED TO READ, THIS IS VIDEOCAST. AS COMMITTEE MEMBERS I WANT TO REMIND YOU YOU MUST ABSTAIN YOURSELVES DURING SPECIFIC DISCUSSIONS WHENEVER YOUR PARTICIPATION DELIBERATIONS ON A PARTICULAR PRODUCT, PROGRAM OR OTHER SPECIFIC MATTER WOULD CONSTITUTE A CONFLICT OF INTEREST OR CREATE APPEARANCE OF ONE. IT IS INCUMBENT UPON YOU TO ADVISE EXECUTIVE SECRETARY AND ABSTAIN FROM ANY PARTICIPATION IN DISCUSSION OR ACTION REGARDING THAT MATTER. IN LIGHT OF CURRENT POLICIES GOVERNING CONFLICT OF INTEREST BASED ON FINANCIAL HOLDINGS AS SPECIAL GOVERNMENT EMPLOYEES WHICH INCLUDE ALL MEMBERS OF THIS COMMITTEE, WE MUST DEPEND UPON YOU TO VOLUNTARILY ABSTAIN YOURSELF DURING ANY AND ALL DISCUSSIONS OF MATTERS THAT COULD CONCEIVABLY IMPACT THE STATUS OF THOSE HOLDINGS. WE TRUST YOUR JUDGMENTS IN THESE INSTANCES. BY LAW QUORUM OF BOARD MEMBERS IS REQUIRED FOR EACH INSTANCE WHICH A VOTE OCCURS IN OPEN SESSION. DURING THIS MEETING TEN APPOINTED MEMBERS MUST BE PRESENT TO VOICE VOTES. NEW MEMBERS WHO ARE NOT CURRENT MEMBERS OF THE ANOTHER NCI ADVISORY BOARD ARE NOT VOTING UNTIL THEY HAVE BEEN CLEARED BY NCI ETHICS OFFICE IN THE OFFICE OF HUMAN RESOURCES. NEXT STATEMENT IS THE PUBLIC COMMENTS STATEMENT AND BASICALLY IT SAYS MEMBERS OF PUBLIC WHO MAY WISH TO EXPRESS VIEWS REGARDING ANY ITEMS DISCUSSED DURING THIS MEETING MAY DO SO BY WRITING DR. SHEILA PRESENTVILLE, EXECUTIVE -- PRINDIVILLE, EXECUTIVE SECRETARY WITHIN TEN DAYS ANY MEETING. ANY WRITTEN STATEMENTS WILL RECEIVE CAREFUL CONSIDERATION. AS REMINDER THIS IS A -- THIS MEETING IS BEING BROADCAST AS CURRENTLY AVAILABLE ON THE NIH VIDEOCAST WEBSITE. NOT SURE HOW MANY PEOPLE ARE BATCHING BUT IT WILL BE ARCHIVED FOR VIEWING LATER IF YOU HAVE SO DESIRE. ALSO WHEN YOUR HAND OUT, IF YOU COULD -- THERE'S ALSO THE LIST OF THE FUTURE CTAC MEETINGS. SO YOU CAN PUT THOSE ON YOUR CALENDARS. THERE IS A QUESTION ABOUT THE NEXT ONE WHETHER IT WILL BE IN PERSON OR VIRTUAL. ALSO IN YOUR HAND OUT HERE IS THE MEETING SUMMARY FROM JULY 11, 2018, I'M PRESUMING YOU GUYS TOOK A LOOK AT THIS. IF YOU HAVE ANY OTHER DISCUSSIONS ON IT OR CORRECTIONS, IF NOT I'LL TAKE A MOTION FOR APPROVAL OF THESE SUMMARIES. SECOND. ALL THOSE IN FAVOR SAY AYE. OPPOSED? GREAT. THE ONE OF THE MOST FUN PARTS OF THIS MEETING THE NCI DIRECTOR TALK TO US. SO WE'RE EXCITED TO HAVE DR. SHARPLESS, OVERVIEW DIRECTOR'S VIEWPOINT HERE. >> THANK YOU FOR COMING TO SPEAK TODAY. FIRST I HAVE SOME SLIDES I WILL GO THROUGH QUICKLY TO PRESERVE TIME AT THE TEND FOR DISCUSSION. I -- AT THE END FOR DISCUSSION. CTAC HAS THINGS TO IS ASK THE DIRECTOR SO I'LL GET TO THAT QUICKLY. ALSO I SHOULD MENTION I LIKE TO START BY THANKING NANCY DAVIDSON FOR RUNNING THIS FOR A WHILE AND TO I THINK PAT FOR TAKING OVER IN ACTING CAPACITY. NCI IS COMING BACK TO SERVE AS DSC REPRESENTATIVE OF CTAC SO SHE'S NOT GOING AWAY, SHE'S BEEN A TREMENDOUS FRIEND AND SUPPORTER OF THE,NANAL CANCER INSTITUTE FOR MANY YEARS AND I PERSONALLY FOUND HER TO BE A GREAT SOURCE OF ADVICE AND ENJOY WORKING WITH HER. UPDATE. I THOUGHT I WOULD GO THROUGH A FEW THINGS THAT ARE OF INTEREST TO THIS GROUP. FIRST TO POINT OUT IS BUDGET SLIDE. BUDGET IS GOOD. IT'S A GOOD TIME TO BE A CANCER RESEARCHER IN THE UNITED STATES. WE HAVE NOW FIVE YEARS OF STEADY INCREASE IN FUNDING. YOU CAN SEE COMPARING 2019 TO 2015, MORE A BILLION DOLLARS INCREASE IN THE APPROPRIATION FOR NATIONAL CANCER INSTITUTE. THE ORANGE BAARS SHOW THE MOON SHOT FUNDING SO 300 MILLION STARTING IN 2017 PEAKING AT 400 MILLION THIS YEAR WHICH IS APPROPRIATE AND THEN NOW NEXT YEAR STARTS TO GO DOWN, DOWN TO 200 MILLION IN 2020 AND STAYS THAT WAY FOR FEW YEARS AND GOES AWAY IN 2023. THIS I THINK IS A TESTAMENT TO THE STRONG BIPARTISAN INTEREST IN CANCER RESEARCH. THIS IS A SENSE THE INVESTMENT OF THE PUBLIC FUNDS AND I THINK ONE OF THE REASONS WHY I GET THE SENSE WHEN I WALK AROUND CONGRESS AND TALK TO MEMBERS ABOUT THE NCI IS THERE'S A CLEAR FEELING WE'RE MAKING PROGRESS. LEGISLATORS HEAR FROM CONSTITUENTS AND READ OPT NEWS ABOUT PATIENTS IN TRIALS THAT ARE SUCCESSFUL SO IS IT'S A LOT OF WHAT DRIVES THIS FAITH IS CLINICAL TRIALS, THE ENTERPRISE OF CLINICAL TRIALS AND THEREFORE WE HAVE TO MAKE SURE THAT THAT OPERATION WORKS AS WE INTEND. A FEW HIGHLIGHTS RELATED TO THE BUDGET, ACTUALLY FIRST OFF HIGHLIGHT TO START WITH IS THE CONTINUED TREND IN CANCER INCIDENCE MORTALITY IN THE UNITED STATES, SHOWN HERE FROM THE ANNUAL DOCUMENT CREATED EVERY YEAR BY THE NCI, CDC AND TESTIMONY AMERICAN CANCER SOCIETY. IT SHOWS AND HAS SHOWN SINCE THE 1990s A STEADY DECREASE IN OVERALL CANCER INCIDENCE AND MORTALITY IN THE UNITED STATES, WITH PARTICULAR NICE PROGRESS IN LUNG CANCER. AND VARIOUS OTHER CANCERS. WHILE GREAT NEWS, IT'S IMPORTANT TO SAY THERE'S UNEVEN PROGRESS, THERE'S A FEW CANCERS WHERE MORTALITY AND INCIDENTS ARE FLAT OR INCREASING LIKE LIVER CANCER. SO THE NCI IS GOOD NEWS BUT ALSO A CHALLENGE SO WE HAVE TO FOCUS AND NOT LOSE THE NUANCE IN COMMUNICATION. THERE'S PROGRESS AGAINST CANCER BUT IT IS UNEVEN AND THEREFORE WE STILL NEED MORE WORK, MORE WORK TO DO IN A FEW AREAS. THE BY PASS SUBJECT IS OUT, THIS IS MY FIRST VERSION OF THAT. THIS IS A DOCUMENT THAT WE PROVIDE EVERY YEAR DIRECTLY TO CONGRESS ASKING DESCRIBING WHAT THE NATIONAL CANCER INSTITUTE WOULD DO IN THESE AREAS WITH ADDITIONAL FUNDING. I COMMEND THIS DOCUMENT TO YOU. WE TRIED TO MAKE IT FOCUSED AROUND WHAT INVESTMENTS MEAN FOR PATIENTS, PATIENT FOCUSED DOCUMENT INCLUDING THE PHOTOGRAPH OF ME WITH MY PATIENTS WHO HAD ACUTE LEUKEMIA I TOOK CARE OF A FEW YEARS AGO AND IS NOW IN ENTERMISSION AND CAME TO VISIT ME NOT LONG AGO. A FEW HIGHLIGHTS FOR THE BUDGET. FIRST WE HAD LAST YEAR THE LARGEST INCREASE TO THE RPG POOL, THIS SUPPORTS RO1s AND PO 1s AND UO 1s, INVESTIGATOR INITIATED SCIENCE SINCE 2003. 2003 WAS A PEAK ENDING BUDGET DOUBLING PERIOD. THE RPG POOL I BELIEVE IS WHERE SOME OF THE REALLY MOST INNOVATIVE IDEAS IN CANCER RESEARCH COME FROM, CRAZY SOUNDING IDEA FROM ACADEMIC INVESTIGATOR THEY SUBMIT AND GET FUNDING FOR AND THOSE ARE THINGS THAT ARE GAME CHANGING CANCER RESEARCH. SO I BELIEVE PRESERVING RPG POOL IS VERY IMPORTANT AND IT'S A REAL ENDORSEMENT FOR THE BASIC SCIENCE WORK THE NCI NEEDS TO CONTINUE TO SUPPORT BECAUSE OF THIS UNEVEN PROGRESS I MENTION. CERTAIN CANCERS WE NEED NEW SCIENTIFIC IDEAS. ANOTHER HIGHLIGHT IS PARTICULAR FOCUS ON EARLY STAGE INVESTIGATORS. SO ESI -- CONGRESS ASKED THE NATIONAL CANCER INSTITUTE TO PAY ATTENTION TO THIS TOPIC TO THE LEGISLATION THAT FUNDED THE MOON SHOT. SO WE HAVE DONE THAT. OUR GOAL WAS TO INCREASE ESI FUNDING BUT MORE THAN 25% IN 2018 WE WELL SURPASSED THAT GOAL, WE'RE STILL TABULATING FINAL NUMBERS BUT WILL BE OVER 30% INCREASE ESI FUNDING. SO THIS IS IMPORTANT BECAUSE OUR ANALYSIS SHOWS THAT EARLY STAGE INVESTIGATORS HAVE A HARD TIME GETTING THAT FIRST GRANT, WRITING A GRANT IS FOREIGN TO THEM, GRANTSMANSHIP PROCESS, ORGANIZING THE DOCUMENT, CREATING A SCIENTIFIC NARRATIVE THAT'S COMPELLING. SO SUPPORT FOR ESIs IS AN AREA WE CAN HELP CULTIVATE EARLY WORK FORCE OF CANCER RESEARCH AND WHERE I THINK WE HAVE GOOD SUCCESS IN 2018. LASTLY, 2019 FOR THE FIRST TIME IN 22 YEARS WE HAVE OUR BUDGET AT THE BEGINNING OF THE FISCAL YEAR SO MUCH MORE COMMONLY, THE FISCAL YEAR BUDGET THAT STARTS OCTOBER 1 WE DON'T GET UNTIL MAY OR JUNE. THAT'S VERY GOOD NEWS. THAT ALLOWS THE NCI MORE TIME TO PLAN HOW WE WILL EXPERIENCE CHANGES IN FUNDING, TAKING MONEY FROM ONE AREA AND PUTTING TOWARDS ANOTHER WITH MUCH LONGER PLAN, THAT IN ITSELF IS ALMOST LIKE A BIT OF SAVINGS, IN ADDITION TO THAT THERE WAS ALMOST $180 MILLION INCREASE TO 2019 BUDGET OF WHICH 100 MILLION IS MOON SHOT FUNDING. SO ABOUT -- ALMOST 80 MILLION-DOLLAR INCREASE TO GENERAL APPROPRIATION. SO THAT'S THE GOOD NEWS, BUT I SHOULD ALSO SAY AT THIS POINT, WE CAN TALK ABOUT THIS MORE WITH QUESTIONS BUT 2019 IS SHAPING UP TO BE A CHALLENGING BUDGET YEAR DESPITE THIS FOR A NUMBER OF REASONS. ONE IS THAT COSTS OF GRANTS, THE GRANTS THAT FINISH ARE SMALLER THAN THE GRANTS THAT START ON AVERAGE AWARD SIZE. ON THE ORDER OF ABOUT $80 MILLION. SO ALMOST THE ENTIRE APPROPRIATION WILL BE CONSUMED BY THE RPG POOL, ANOTHER FACT OF LIFE IS THAT WHILE WE FUND MORE AND MORE RO1s EVERY YEAR, THE RATE OF INCREASING NEW APPLICATIONS EXCEEDS OUR ABILITY TO FUND NEW APPLICATIONS. SO IN 2017 WE HAD A 12% INCREASE IN NEW RO1 APPLICATIONS, IN 2018, 11% AND THIS YEAR WE MODEL 6 TO 7% INCREASE SO 30% INCREASE IN RO1 APPLICATIONS THE LAST FEW YEARS. WHILE WE INCREASE THE RPG POOL NEW APPLICATION FUNDS IN RPG POOL, OVER THAT PERIOD, 30% IS NOT SOMETHING WE CAN AFFORD. SO CITY TALK BUDGET -- A TOUGH BUDGET YEAR I MEAN PAY LINES I DO NOT EXPECT TO GO UP. THERE THEREBY THE SAME OR PERHAPS WORSE IN 2019 COMPARED TO 2018. BUT WE ARE WORKING THROUGH THAT, WILL BE A WHILE BEFORE WE MAKE A FORMAL ANNOUNCEMENT ABOUT PLANS FOR FUNDING RPG POOL IN 2019. ANOTHER HIGHLIGHT FOR THE YEARS IS CLEARLY A BIG YEAR FOR IMMUNOTHERAPY. WE HAD PUBLICATIONS ON 3-D PATIENTS WITH ADVANCE SOLID TUMORS USING CELLULAR IMMUNOTHERAPY. WE HAD A ALBANY PRIZE THIS YEAR FOR THIS DISTINGUISHED GROUP OF FORMER CURRENT NCI SUPPORTED INDIVIDUALS. THEN OF COURSE JIM ALLISON AND WINNING THE NOBEL PRIZE FOR WORK CHECK POINT INHIBITORS SO IMMUNOTHERAPY HAS CONTINUED TO AMAZE, AND BE DEVELOPED, IT SHOWED ACTIVITY IN NEW SETTINGS AND APPROVALS AND NCI CONTINUES TO INVEST IN CLINICAL TRIALS RELATED TO IMMUNOONCOLOGY. ANOTHER HIGHLIGHT TO MENTION IS FDA APPROVAL OF (INAUDIBLE) P THE EXCLAMATION POINT ON A LONG DISTINGUISHED BODY OF WORK FROM PAST AND -- IRA PASTAIN AND COLLEAGUES IN THE INTRAMURAL PROGRAM SO THE CONCEPT OF LINKING ANTIBODIES TO TOXIC MOLECULES WAS DEVELOPED BY HIM, THIS SPECIFIC ANTIBODY, C 22 SPECIFIC TOXIN T PSEUDOMONA TOX, PRODUCTS OF THE INTRAMURAL PROGRAM AND CLICK TRIALS WERE DONE IN THE CLINICAL CENTER WERE DONE BY ROBERT CREIGHTON SO THIS IS A INTRAMURAL STORY COMMERCIALIZED BY MED IMMUNE ASTRA ZENECA AND IS NOW APPROVED FOR PATIENTS IN THIS CANCER. SO I THINK THIS IS ONE OF MANY I CAN PROVIDE ABOUT QUALITY OF SCIENCE AND THE NCI INTRAMURAL PROGRAM AND HOW CERTAIN CAPABILITIES IN THIS INTRAMURAL PROGRAM ARE NOT PRESENT ELSEWHERE. TAYLOR X IS A GOOD THING TO MENTION BECAUSE IT MAKES THE STATEMENT WHILE I SAID CLINICAL TRIALS NATURE ONCOLOGY IS CHANGING AND THE FOCUS IS GOING AWAY FROM LARGE, LARGE TRIALS TO SMALLER MOLECULARLY TARGETED TRIALS, IT'S STILL IMPORTANT TO NOTE THE NCI NEEDS SUPPORT LARGE CLINICAL TRIALS BECAUSE THEY ARE CERTAIN KINDS OF TRIALS THAT NO ONE ELSE IS LIKELY TO DO THAT ARE VERY IMPORTANT FOR PATIENTS. THIS IS SUCH AN EXAMPLE. SO THIS IS A TRIAL THAT TOOK OVER A DECADE ENROLLING 10,000 PATIENTS TO SEE IF ASSIGNING PATIENTS TO CHEMOTHERAPY, PLUS HORMONAL THERAPY PLUS HORMONAL THERAPY ALONE, ER POSITIVE BREAST CANCER WOULD -- AS MENTIONED A LARGE TRIAL WITH FOLLOW-UP, THE ANSWER IS DECIDEDLY ONE CAN SKIP CHEMOTHERAPY IN THIS POPULATION, INTERMEDIATE RISK PATIENTS BASED ON RNA RISK SCORE. THIS IS GREAT NEWS FOR PATIENTS. THIS ALLOWS WOMEN WITH ER POSITIVE TO DO THAT EXPERIENCE A LOT OF SIDE EFFECTS HAIR LOSS, ET CETERA BUT ALSO SAVES MONEY SO IT'S GREAT TO MINIMIZE TOXICITY AND TO SAVE THE HEALTHCARE COSTS. IT'S A DEESCALATION TRIAL, A TRIAL INDUSTRY EFFORTS ARE NOT GOING TO TAKE ON, NOT REALLY COMPANIES TO SHOW LESS OF THEIR DRUG IS GOOD ADS HIGHER DOSE. IT'S WORTH POINTING OUT THE DEESCALATION TRIALS ARE HARD TO DO SO THE NCI FUNDED ANOTHER HIGH PROFILE TRIAL IN HPV RECORDED AT -- THAT SHOWED IN THAT CASE THE OLD MORE TOXIC REGIMEN RADIATION PLUS PLATINUM IS BETTER THAN THE NEW LESS TOXICS BUT NOW WE KNOW LESS EFFECTIVE REGIMEN OF RADIATION PLUS CETUXIMAB. THAT'S A DEESCALATION TRIAL ARE WHERE THE NEW ARM IS IS INFERIOR AND WHY WE NEED TO WORK THROUGH THESE TOPICS IN THE NCI. ASPRE IS A STUDY SUPPORTED THROUGH DCP ALONG WITH NATIONAL INSTITUTE OF AGING THIS IS A LARGE TRIAL IN ALL COMERS OVER AGE 70, PATIENT WHOSE DIDN'T HAVE A REASON TO BE ON ASPIRIN AND THE IDEA TO SEE IF IT REDUCED ALZHEIMER'S, STROKE, CARDIOVASCULAR EVENTS AND CANCER. THIS AND OTHER ASPIRIN TRIALS WERE DUE TO SINGLE ISSUE IN NEW ENGLAND JOURNAL TWO WEEKS AGO, ALL ASPIRIN AND THE SUMMARY OF ALL THE TRIALS IS THAT IT WAS A STRONG -- PRIMARY PREVENTION IN ANY POPULATION, CERTAINLY NOT OVER AGE 70, IF ANYTHING WE SAW MORTALITY EXCESS. STATISTICALLY SIGNIFICANT INCREASE IN CANCER RELATED DEATH OR OTHER TRIALS IT WAS JUST EVEN, NO BENEFIT TO ASPIRIN USE IN TERMS OF MORTALITY. BECAUSE EXCESS BLEEDING AND EXCESS CANCER. SO THIS IS THE PROBLEM WITH PRIMARY PREVENTION. I WOULD LIKE TO MENTION SOME BAD NEWS HERE, I LONG HAVE BEEN INTERESTED IN THE TOPIC OF INTERACTION TOPIC AGING THAT'S A RESEARCH INTEREST OF MINE. I TRIED TO TO US CAN ON OTHERS IN CANCER AGING I THOUGHT THERE WAS A DERTH OF CLINICS WHO WERE INTERESTED IN TOPIC OF INTERACTION OF CANCER AND AGING AND ONE OF THE REALLY WONDERFUL PEOPLE IN THIS FIELD IS ALREADY HERE, CITY OF HOPE I WAS INFORM WAS IN AN ACCIDENT LAST NIGHT. AND PASSED AWAY. SO THERE IS TREMENDOUS LOSS FOR THE FIELD. ARTY WAS A WONDERFUL SCIENTIST GREAT COLLABORATOR. CERTAINLY WE NEED MORE PEOPLE LIKE HER WITH THIS INTEREST. MOVING ON SOME OTHER NEW PROJECTS TO TALK ABOUT. THAT I THINK ARE LIKELY OF INTEREST IN THIS CANCER. WE WERE ABLE TO FUND THROUGH SUPPLEMENT MECHANISM A FEW INTERESTING TOPICS THIS YEAR. AS MANY KNOW SUPPLEMENT MECHANISMS ALLOW THE NCI TO PROVIDE MODEST FUNDS TO NEW TOPICS WITH RAPID TURNAROUND. IN PARTICULAR, VARIETY OF REASONS WE SUPPORTED SOME WORK IN GBM SO SINGLE CELL SEQUENCING EFFORTS IN PEDIATRIC AND ADULT GLIOBLASTOMA SHOWN HERE. WE ALSO USE SUPPLEMENT FUNDING FOR QUESTIONS, IN THE CANCER CENTERS AND RURAL VERSUS URBAN RESEARCH. WE AWARDED A NEW SCORE IN LIVER CANCER, AS I MENTIONED LIVER CANCER IS A CANCER IN THE UNITED STATES THAT IS INCREASING IN FREQUENCY MORTALITY. THE EPIDEMIOLOGY IS CHANGING IN A FASCINATING WAY WITH LESS LIVER CANCER ASSOCIATED WITH DECREASE INCIDENCE FROM VIRAL HEPATITIS BUT INCREASING FROM ALCOHOL USE AND OBESITY. AND SO THIS CHANGING PATTERN LIER CANCER ARE AN INTERESTING PROBLEM GIVEN THE IMPORTANCE OF INCREASE IN MORTALITY IN THE UNITED STATES. THIS IS ALSO SCORE IS ALSO MATCHED BY UO 1s ON THIS TOPIC SO I THINK FAIR TO SAY RESEARCH PORTFOLIO IN LIVER CANCER HAS BEEN THIN IN THE PAST. WE ARE WORKING TO RECTIFY THAT IN A DIRECT WAY. I THINK A BIG DEAL FOR CANCER PATIENTS LAST YEAR WAS THE CMS DECISION TO COVER NEXT GENERATION SEQUENCING. THIS WAS A COMPLICATED REGULATORY PROCESS THAT INCLUDED THE FDA AND CMS, THE FDA SIMULTANEOUSLY APPROVING THIS WITH CMS COVERAGE DECISION, THIS PROCESS WAS A GOOD ONE. THE NCI PLAYED ADVISORY ROLE IN THE FINAL POLICY. WATCHING THIS HAPPEN FROM THE INSIDE IS MY FIRST FEDERAL TYPE PROCESS EFFORTS. I WAS IMPRESSED, THIS WAS A GOOD DECISION, FELT ACADEMIC IN THE BEGINNING, BUT AFTER MONTHS OF DISCUSSION DECISION WAS MADE, VERY MEANINGFUL PREVENTION. MEDICARE PATIENTS WHO MEET CMS CRITERIA ADVANCE SOLID TUMOR WHO FAILED STANDARD OF CARE ARE ELIGIBLE FOR SEQUENCING THROUGH FDA APPROVED ASSAY SUCH AS THE FOUNDATION MEDICINE ASSAY, NOW SEVERAL ACADEMIC LABS ARE PURSUING APPROVAL FROM ASSAY. SO I THINK IT'S DEMOCRATIZES PRECISION ONCOLOGY OUTSIDE COMPLEX OF CLINICAL TRIALS THROUGHOUT THE UNITED STATES AND IT'S GOOD NEWS FOR CANCER PATIENTS. THINGS GOING ON WITH MOON SHOT WE HAD A FOLLOW-UP WITH A PANEL LAST WEEK TO DISCUSS PROGRESS WITH THE MOB SHOT. A LITTLE -- MOON SHOT. WE ARE TWO AND A HALF YEARS IN. THE MOON SHOT IS I BELIEVE YOU RECALL THE VISION OF IT WAS FRAMED BY BLUE RIBBON PANEL, THAT IDENTIFIED TEN PRIORITY AREAS. THESE WERE AREAS THE IDEA WAS A BIT OF INVESTMENT, RAPIDLY ACCELERATE PROGRESS SO THE MOON SHOT FUNDING WASN'T ENVYINGED TO TRAINING OR SCIENCE BUT FUND RAPID TRANSLATION OF ALMOST READY FOR THE CLINIC IDEAS IN THESE TEN AREAS. WE NOW HAD FUNDING ANNOUNCEMENTS IN INTRAMURAL AND EXTRA MURAL PROGRAMS IN ALL TEN AREAS. SOME LARGER THAN OTHERS, BUT WE WERE TRYING TO DEVOTE SIGNIFICANT EVIDENCE IN ALTERNATE AREAS. NCI TRIED TO ADHERE TO THAT DOCUMENT. THAT VISION. WE HAVE TRIED TO FIND BEST SCIENCE TO SUPPORT SCIENCE IN THOSE TEN AREAS AND HAVE COME UP WITH GREAT STUFF. I'M SURE MOST HAVE BEEN TO THE WEBSITE AND FUNDING ANNOUNCEMENTS IN 2017, 2018, MORE COMING IN 2019. SOME EXAMPLES OF THINGS WE FUND IN RECENT PAST ARE ADULT AND PEDIATRIC IMMUNOTHERAPY NETWORKS, TRANSLATIONAL NETWORKS IN IMMUNOONCOLOGY, WORK THROUGH VARIETY OF NETWORKS AND COOPERATIVE GROUPS AND DRUG RESISTANCE EFFORTS IN RARE TUMOR PATIENT ENGAGEMENT FUSION ONCO PROTEINS AND PEDIATRIC CANCER FOR EXAMPLE. SO A LOT OF IMPORTANT STUFF RELATED TO THE INITIAL VISION BUT ONE THING TO POINT OUT MOON SHOT IS SHOWN HERE, THAT AS I ALLUDED TO EARLIER, THE FUNDING DID THIS FIRST COUPLE OF YEARS, NOW PEAKS THIS YEAR AND THEN GOES DOWN FOR FOUR YEARS THEN OFF. SO THIS IS ONE OF THESE THINGS WE CALL GOVERNMENT A GOOD PROBLEM TO HAVE. IT IS A GOOD NEWS THAT THE FEDERAL GOVERNMENT HAS GIVEN US $1.8 BILLION MORE TO SPEND ON CANCER RESEARCH IN THESE INTERESTING TOPIC. THE NCI CERTAINLY GLAD TO HAVE THAT OPPORTUNITY BUT THIS FUNDING DECREASED FROM 400 TO 200 AND 200 OFF SO SORT OF 4 -- I MEAN 2, 200 MILLION-DOLLAR CUTS OVER THE NEXT FOUR YEARS IS SOMETHING NCI HAS TO PLAN FOR, CUTS. SOMETHING TO PLAN FOR BECAUSE MOON SHOT IS CREATING WONDERFUL INFRASTRUCTURE RESEARCH COLLABORATIONS, EFFORTS IN VARIOUS TOPICS WE WANT TO CONTINUE AFTER THE FUNDING ENDS IN 2023. THE NCI WILL HAVE TO FIGURE OUT WAYS TO SUPPORT THE GREAT THINGS MOON SHOT IS CREATING TODAY IN THE OUTYEARS ONCE MOON SHOT ENDED. ONE THING CONGRESS IN ITS WISDOM KNEW THIS WOULD BE A PROBLEM FOR THE NATIONAL CANCER INSTITUTE MOVE AND BUST CYCLE OF FUNDING, MAYBE FUNDS IN OF YEAR FUNDING, THIS ALLOWS US TO PREPAY SOME GRANTS, MORE THAN ONE YEAR IN INITIAL FUNDING POLES AND CARRY OVER FUND IN A FEW INSTANCES. WE HAVE TAKEN ADVANTAGE OF BOTH CAPABILITIES TO SMOOTH OUT THE ISSUES BUT EVEN DESPITE THAT AS I SAID, THESE DECREASES IN FUNDING POSED CHALLENGES FOR THE NCI. FEW OTHER CHALLENGES TO MENTION AHEAD. WE HAVE DISCUSSED A BIT AD HOC WORKING GROUPS TO CTAC T. GLIOBLASTOMA ROSTER IS OUT AND CHAIRS ARE SHOWN HERE. THESE REPORT TO THE NCAB,. AND THE RADOC WORKING GROUP IS IN PROCESS. WE'RE STILL GETTING A SLATE FOR THAT. AS YOU RECALL ONE OF THE RECOMMENDATIONS OF THE SCORE RE-EVALUATION PROCESS WAS THAT NCI GET ADDITIONAL ADVICE ON GREAT TRANSLATIONAL OPPORTUNITIES. WE DECIDED THAT PROBABLY GO BETTER IF THERE WERE SOMEWHAT FOCUSED BY TOPIC AND WE IDENTIFIED TWO INITIAL TOPICS TO TRIAL WE DON'T ENVISION THESE TO BE THE LAST TWO WE DO. THIS PROCESS IS USEFUL I SUSPECT ADDITIONAL WORKING GROUPS TO IDENTIFY TRANSLATIONAL OPPORTUNITIES FOR THE NATIONAL CANCER INSTITUTE. LOT OF TRANSITIONS IN LEADERSHIP. WE HAVE AN ACTIVE SEARCH GOING, FOR DIRECTOR OF CENTER FOR GLOBAL HEALTH, NOW THAT TED TRIMBLE HAS GONE TO NEW ROLE LIAISON TO WHO FOR THE NCI, THE CENTER FOR BIOINFORMATICS IS VERY IMPORTANT JOB NCI IN TERMS OF DATA STRATEGY GOING FORWARD FOR NCI WE HAD A HUGE SPEND ON IT, BIG DATA AND THIS IS REALLY IMPORTANT LEADERSHIP POSITION I EXPECT WE'LL FILL SOON. CTAC, JEFF ABRAMS IS HERE BUT PLANS TO RETIRE SOON SADLY FOR THE NCI, AND NEED TO LOOK FOR REPLACEMENT THERE, BARRY KRAMER HERE LET US KNOW LAST WEEK WE'LL RETIRE IN JANUARY FROM DCP, THIS IS A CRITICAL POSITION GIVEN LARGE PORTFOLIO OF THE NCI CANCER PREVENTION EARLY DIAGNOSIS AND NATIONAL CHANGES IN THE TOPIC OF PREVENTION. I THINK BARRY DESERVES APPLAUSE. [APPLAUSE] >> TREMENDOUS LEADER FOR THE NCI FOR A LONG TIME. THAT IS NOT TO SAY JEFF -- I THINK WE HAVE DONE THAT BEFORE BUT APPLAUSE FOR JEFF. [APPLAUSE] FREDERICK NATIONAL LABS, IMPORTANT SET OF CAPABILITIES, HAS POSITION OPEN FOR INSTITUTE DIRECTOR NCI EMPLOYEE TO WORK WITH THE EMPLOYEES FREDERICK IS RUN BY -- AS MANY OF YOU KNOW. THIS IS VERY IMPORTANT TO MAKE FREDERICK OPTIMAL USE FOR THE NCI. WE EXPECT TO ANNOUNCE POSITIONS DIRECTOR SOON. THIS HAS BEEN TIME BEING POSITION IS FILLED BY DOUG ABLY BUT DOUG WOULD LIKE TO SEE THIS POSITION FILLED. I HAVE SPOKEN TO THE GROUP BEFORE ABOUT KEY FOCUS AREASES THAT IDENTIFY A PROCESS OF LISTENING AND LEARNING AND GOING AROUND NATIONALLY. I WON'T GO INTO THIS TOO MUCH UNLESS THERE'S SPECIFIC QUESTIONS, WE TALKED ABOUT THE PAST. MAYBE I WILL HIGHLIGHT ONE ITEM HERE IN THE CLINICAL TRIALS AREA WHICH IS IN 2018 I SPOKE TO MANY OF INVESTIGATORS INVOLVED IN THE NATIONAL CLINICAL TRIALS NET WORK NCTN AND OTHER NETWORKS AND GOT A CLEAR SENSE WHILE NCTN WAS VITAL AND IMPORTANT PART OF WHAT NCI DOES, IT WAS UNDERRESOURCED. I AGREED WITH THAT AND LEARNED HISTORY HOW THAT CAME ABOUT. AND IN 2018 WE WERE ABLE TO PUT NEW FUNDS INTO THE NCTN TO THE TUNE OF $10 MILLION, MOSTLY TO ALLEVIATE COST DISCREPANCIES IN PER PATIENT FUNDING. SO PHARMA TRIALS REIMBURSE AT HIGHER RATE THAN NCI TRIALS AND WE ARE TRYING TO MAKE THE DELTA SMALLER THROUGH ADDITIONAL FUNDING. I HOPE WE WILL BE ABLE TO DO THAT IN 2019. THAT IS A -- THAT IS A TOUGH BUDGET YEAR FOR US. BUT THIS IS AMONG HIGH PRIORITIES. I DON'T BELIEVE 10 MILLION-DOLLAR WAS ENOUGH, WE NEED TO DO MORE. THE REASON THIS GROUP APPRECIATES WE HAVE TO DO IT SOMEWHAT SLOWLY BECAUSE EVERY NICKEL WE PUT IN HAS OUTYEAR COSTS SO RATHER THAN MONEY AT ONCE WE TRY TO DO DATE OVER COUPLE OF YEARS SO HOPE WE WILL BE ABLE TO DO THAT IN 2019 AS WELL AS WE SEE THAT SPENDING PIPELINE. SO THAT'S MY REMARKS THIS MORNING. I WOULD BE HAPPY TO TAKE QUESTIONS, I VERY MUCH -- I WILL BE BY THE WAY ABLE THE STAY AROUND FOR THE PANCREATIC PRESENTATION NEXT, VERY IMPORTANT TOPIC TO THE NCI SO I'LL BE AROUND A LITTLE WHILE BUT HAVE TO LEAVE AFTER THAT. ANY QUESTIONS? >> WE HAVE ABOUT TEN MINUTES FOR QUESTIONS FOR DR. SHARPLESS. BEFORE YOU DO, I WANT TO -- I FEEL COMPELLED TO SAY THIS ABOUT -- I KNEW HER THROUGH THE ASCO LEADERSHIP DEVELOPMENT PROGRAM, SHE WAS A SUPER STAR THERE. BECAME THE FIRST PERSON PART OF THE AS CO BOARD FROM THAT GROUP, WAS THE YOUNGEST RECIPIENT OF THE BJ KENNEDY AWARD. SHE WAS A LADY THAT WAS FULL OF WISDOM AND GRACE AND THE MOST GENUINE PERSON I EVER KNEW. THE WORLD OF CANCER IS SADDENED BY HER LOSS. QUESTIONS. >> ANY COMMENTS ON NCI GLOBAL INITIATIVES? I BELIEVE EARLY ON YOU TALKED HOW IMPORTANT THEY ARE AND DO YOU HAVE ANY TRACK FORWARD HOW TO ADDRESS IT? YES. THIS IS SOMETHING WE SPEND A LOT OF TIME ON. I THINK PER CONVERSATION I HAD WITH DR. VARMUS BEFORE I STARTED, I ASKED HAROLD WHY DOES THE NCI HAVE SUCH A BIG AND DIVERSE PORTFOLIO IN GLOBAL ONCOLOGY? THIS IS BEFORE I WAS SWORN IN, NOT FEDERAL OFFICIL AT THE TIME. SO I ASKED WHY DO WE HAVE THAT? HAROLD SAID VERY FORCEFULLY, WE THIS. CANCER IS AN INCREASING KILLER WORLDWIDE AND THE SCIENCE WE DO BENEFITS ALL PATIENTS NOT JUST AMERICAN PATIENTS. THAT'S WHY WE DO IT. I SAID YEAH, YEAH, I GOT THAT BUT HOW WOULD I EXPLAIN THIS TO A SKEPTICAL MEMBER OF CONGRESS? WHY IS THIS SOMETHING THE NCI NEEDS TO DO? HAROLD'S RESPONSE TO THAT WAS YOU SHOULD PROBABLY ASK TONY FAUCI FOR ADVICE ON THAT TOPIC. WHO RUNS NIGHED IDEA AND MADE THAT ARGUMENT ABOUT HIV FUNDING OR EBOLA OR FLU. I HAVE TAKEN HIM UP ON THAT, I HAD A NUMBER OF CONVERSATIONS WITH FRANCIS COLLINS, ROGER GLASS AND PEOPLE INTERESTED IN TOPIC OF GLOBAL CANCER RESEARCH. I THINK IT IS A VERY EASY TO DEFEND USE OF FUNDS T. RESEARCH TOPICS FOR VARIETY OF REASONS WILL HAVE TROUBLE DOING IN THE UNITED STATES BUT WE WANT TO KNOW THE ANSWER TO CERTAIN QUESTIONS. THERE ARE DISEASES THAT ARE NOT SUFFICIENTLY COMMON LIKE TRIALED CHAD BRAIN CANCER, TO MAKE PROGRESS THERE WE NEED INTERNATIONAL COLLABORATION. ALSO USAGE OF DRUGS IN DIFFERENT PHASES OF DISEASE SO YOU MIGHT BE ABLE TO DO IMMUNOONCOLOGY TRIALS IN HODGKIN'S DISEASE IN OARY-- OTHER COUNTRIES THAN IN THE UNITED STATES. WHAT DRIVES BIOLOGY OF SQUAMOUS CANCER IN SOUTHEAST AFRICA? IT ANOINTERSING PATHOGENESIS IN CANCER ONE OF THE GREAT ETIOLOGIC STORIES IN CANCER RESEARCH SO WE NEED TO DO THIS, IT'S A GOOD THING TO DO, AND WE'RE GOING TO DO IT. BUT HAVING SAID THAT, IT TURNS OUT TO BE REALLY HARD. THERE IS A IMMENSE NEED FOR RESEARCH IN GLOBAL CANCER. THE NCI IS ROUTINELY APPROACHED BY OTHER COUNTRIES THAT WOULD LIKE US TO PARTICIPATE IN ACTIVITIES AND EFFORTS INTERNATIONALLY, SOME OF THOSE PROPOSALS ARE STRONG THINGS WE SHOULD BE DOING. SOME OF THOSE ARE LESS SO. SO PRIORITIZING THOSE EFFORTS IS A CHALLENGE BECAUSE THERE IS A GLOBAL DEMAND FOR OUR TIME. THIS AFTERNOON FOR EXAMPLE I'M MEETING WITH SCIENTISTS FROM CRUK TO TALK ABOUT OPPORTUNITIES TO CO-FUND EFFORTS OR CO-SUPPORT EFFORTS BETWEEN CRUK AND NCI BECAUSE OF THOSE KINDS OF TOPICS I MENTIONED WHERE JOINT COLLABORATION IS BETTER THAN ANY SINGLE COUNTRY ALONE. SO PLY YOUR ADVERTISING EFFORTS IS A -- PRIORITIZING EFFORTS IS A BIG PROBLEM IN CENTER FOR GLOBAL HEALTH AT THE NCI. HOW TO GET CERTAIN ACTIVITIES SUFFICIENTLY DONE AS YOU ARE WELL AWARE, DOING STUDIES IN OTHER COUNTRIES CAN BE CHALLENGING, SAMPLE SHARING IS DIFFICULT, THE LEVELS OF SCRUTINY FROM LOCAL INSTITUTION ETHICAL REVIEW BOARDS IS DIFFERENT AND CULTURE TAKEN INTO ACCOUNT SO MAKING SURE WE PROVIDE INFRASTRUCTURE TO SUPPORT BIG PORTFOLIO OF RESEARCH IN THE NCI IS AN IMPORTANT MISSION FOR THAT CENTER AS WELL. AS I MENTIONED, CGH WILL BE LOOKING FOR A NEW DIRECTOR, I EXPECT IT TO START SOON. MY IDEA THERE IS IT WILL BE A GREAT SCIENTIST, PHYSICIAN OR Ph.D. OR BOTH WHO IS INTERESTED IN THE PROBLEM OF GLOBAL ONCOLOGY AND REALLY UNDERSTANDS IT, EITHER FROM WITHIN NCI OR EXTRAMURALLY, DOESN'T MATTER, IT'S AN OPEN SEARCH BUT THAT PERSON WILL BE CRITICAL. TO SETTING PRIORITIES, TO MAKING SURE THAT THE SIGNIFICANT RESOURCES WE'RE USING ON THIS TOPIC ARE OPTIMALLY SPENT TO ANSWER THE KEY QUESTIONS T. >> I WANT TO MAKE ONE CLARIFICATION. I JUST SORT OF LOOKED AT HIM BUT THE -- WORKING GROUP REPORTS TO CTAC. RADIATION ONCOLOGY. >> I NEW -- KNEW IT REPORTED TO SOME COMMITTEE. THAT'S WHAT I LEARNED ONE YEAR FEDERAL OFFICE. WORKING GROUP REPORTS TO SOMEBODY. >> A QUICK QUESTION. WHEN YOU SHOWED THE INCREASE -- GREATEST INCREASE OF CANCER DEATH, IS IN NON-MELANOMA SKIN CANCER -- >> ARE YOU TALKING ANNUAL REPORT TO THE NATION DATA? >> GO BACK NEXT SLIDE. SURPRISES ME DO YOU KNOW ANYTHING ABOUT THAT? >> I WOULD HAVE TO LOOK INTO THIS. JEFF, CAN YOU SAY ANYTHING ABOUT --? >> THIS MAYBE SUCH A RARE CAUSE -- IT HAS AN ASTERISK BESIDE IT, I HAVE TO LOOK INTO IT. I HAVE TO LOOK INTO THAT. THE ONES WE ARE A BIT MORE FOCUSED ON BECAUSE THEY ARE BECOMING IMPORTANT CAUSE OF MORTALITY IN THE UNITED STATES, LIVER OBVIOUSLY ENDOMETRIAL IN WOMEN, PANCREAS CANCER, BRAIN CANCER, THOSE ARE AREAS WHERE I THINK FEELS LIKE WE SHOULD BE MAKING MORE PROGRESS AND WE ARE NOT. THEY ARE IMPORTANT CAUSE OF MORTALITY IN THE UNITED STATES. >> WHAT QUESTIONS DO YOU HAVE FOR US? HOW CAN THIS COMMITTEE SERVE YOU WELL? >> I THINK THE -- A PROBLEM -- I MAKE PROBABLY A LOT OF QUESTIONS MORE THAN I CAN COVER IN FIVE MINUTES BUT I HAVE THIS SORT OF WHEN I TALK CLINICAL TRIALS, AS ONE KEY FOCUS AREAS, I HAVE THIS SOMEWHAT CAVALIER REMARK, TO ME IT SOUNDS CAVALIER, THAT THE NCI SHOULD BE DOING CERTAIN KINDS OF TRIALS AND NOT OTHER KINDS OF TRIALS. WE SHOULD BE COLLECTING DATA AND AGGREGATING IT IN A WAY PROSPECTIVELY THAT MAKES IT USEFUL, EVERYBODY AGREES WITH THOSE TWO STATEMENTS BUT THE DETAILS OF THOSE STATEMENTS ARE VERY COMPLEX. WHAT EXACTLY ARE THE TRIALS THAT ARE NCI TRIALS VERSUS TRIALS THAT WE SHOULD DEFER TO INDUSTRY? OR WHERE WE COLLABORATE WITH INDUSTRY. WE HAVE ALL THREE MECHANISMS FULLY SUPPORTED COLLABORATIVELY OR DEFER COMPLETELY INDUSTRY SO I MENTION DEESCALATION TRIALS, I MENTION COMPLEX MULTI-MODALITY TRIALS, RADIATION, SURGERY AND MULTIPLE AGENTS, ALSO TRIALS TWO DRUGS COMES FROM TWO COMPANIES, NCI IS GOOD FIT BECAUSE OF ABILITY TO SERVE ON AS BROKER BUT AS TRIALS BECOME MORE EXPENSIVE AND ABILITY TO GET TRIALS UP AND RUNNING AND STARTED IS ALWAYS CHALLENGING, THEN IT'S REALLY IMPORTANT FOR THE NCI TO DEVOTE ITS EFFORTS TO THE RIGHT TRIALS WE HAVE TO DO VERSUS THOSE WE LIKE TO DO. THAT WE THINK ARE INTERESTING. THEN ALSO THE TOPIC OF I THINK DATA ANALYSIS RELATED TO CLINICAL TRIALS IS TWO PROBLEMS, PROBLEM A IS HOW TO GET BETTER DATA FROM THE TRIALS IN STUDIES WE HAVE ALREADY DONE, THE RETROSPECTIVE PROBLEM, HOW DO YOU MINE THE LDHR AND UNDERSTAND PROGRESSION OR RESISTANCE AND THESE THINGS WE CARE ABOUT BUT NOT ROUTINELY CAPTURED IN STANDARD PATIENT MEDICAL RECORD AND ALSO SOMETHING NOT CAPTURED IN A CLINICAL TRIAL, OUTCOME OF INTEREST HAPPENS AFTER WITH THE FIRST PROGRESSION OR WHATEVER. SO GETTING BETTER RETROSPECTIVE DATA IS A PROBLEM BUT ALSO A PROBLEM WE HAVEN'T TALKED ABOUT ADS MUCH BUT IS -- AS MUCH BUT INTERESTING CONCERN, LET'S JUST SAY WE WANTED THE FIX HOW WE COLLECT DATA TODAY, WITHIN ANY TRIAL NCI FUNDS, HOW SHOULD WE FIX -- HOW SHOULD WE DO THAT? WHAT WAS THE PROSPECTIVE SOLUTION SUCH THAT FIVE YEARS FROM NOW YOU WON'T BE STUCK IN THE SAME BOAT HAVING DATA WE CAN'T MINE EFFICIENTLY. HOW DO WE MAKE CLINICAL TRIALS DATA COLLECTION MACHINE READABLE IF YOU WILL BUT IN A WAY THAT IS NOT IN A POSITION? I HAVE READ THE NEW YORKER PIECE THIS WEEKEND ON EPIC BURN OUT, I BELIEVE THAT, MY WIFE IS THE CLASSIC 2 IN THE MORNING IN HER PAJAMAS IN HER EPIC NOTES PHYSICIAN SO I KNOW THE BURDEN THAT EHR HAVE CAUSED FOR MODERN MEDICAL ONCOLOGISTS FOR EXAMPLE. I DON'T WANT TO INCREASE THAT BY SAYING YOU HAVE TO FILL OUT 75 FORMS FOR THE NCI FOR ANY PATIENT ON TRIAL. BUT I ALSO WANT TO MAKE THE DATA -- IF WE'RE PAYING THESE TRIALS EXPENSIVE, WE LIKE USE THEM FOR PURPOSES OTHER THAN JUST A SINGLE FIRST PRIMARY END POINT. SO MAKING THE DATA PROSPECTIVELY COLLECTIBLE IN CLINICAL TRIALS IN WAY THAT WORKS IN CLINICAL PRACTICE BUT ALSO USED IN NCI IS REALLY IMPORTANT QUESTION. THOSE TWO. THANK YOU. >> ALL RIGHT. THE NEXT SESSION HAS TO DO WITH THE PROGRESS REPORT ON PANCREATIC CANCER, DUCTILE RESEARCH WORKING GROUP, IT'S GOING TO BE PRESENTED BY JIM ABBRUZZESE. JIM UNFORTUNATELY HAD A SITUATION AT HOME THAT DIDN'T ALLOW HIM TO COME AND HE WAS GOING TO PRESENT HERE THROUGH WEBCAST. WE FOUND OUT THAT THE WEBCAST ISN'T WORKING SO I THINK HE'S ON THE PHONE. ARE YOU ON THE FOB? -- PHONE? >> CAN YOU HEAR ME OKAY? I WANT TO MAKE SURE THAT I -- >> WE CAN HEAR YOU WELL. >> OKAY. I WANT TO MAKE SURE I CAN CONTROL THE SLIDES. WHICH I'M -- HANG ON. LOOKS GOOD. >> LET ME FRAME THIS A LITTLE BIT. >> GO AHEAD. >> THE PURPOSE OF THIS SESSION IS PROVIDE UPDATE ON ACTIVITIES OF THE PDAC PROGRESS WORKING GROUP, THIS GROUP WAS CONVENED SOMETIME AGO TO ADVISE THE NCI AND THE RELEVANCE OF INITIATIVES OF PANCREATIC CANCER SCIENTIFIC FRAMEWORK DEFINED FIVE YEARS AGO. REALLY TO LOOK AT TRYING TO HELP IDENTIFY NEW OPPORTUNITIES FOR PDAC THIS WAS PART OF THE REQUIREMENT OF RECALCITRANT CANCER RESEARCH ACT OF 2012. THE FINDINGS OF THIS GROUP WILL ENCYST -- ASSIST THE NCI UPDATING THE PDEC SCIENTIFIC FRAMEWORK WHICH ITS DUE MARCH 1 OF 2019. THE GROUP MET A FEW WEEKS AGO. DR. ABBRUZZESE WILL PRESENT HIGHLIGHTS OF THAT MEETING AND SCIENTIFIC ADVANCES. THE WORKING GROUP REPORT IS NOT YET FINALIZED BUT WHEN IT IS IT WILL BE CIRCULATED AMONG THESE MEMBERS OF THE THIS COMMITTEE FOR COMMENT AND ACCEPTANCE. >> JIM TAKE IT AWAY. >> THANKS VERY MUCH, APPRECIATE THE OPPORTUNITY TO SPEAK TODAY TO UPDATE THE COMMITTEE ON PROGRESS BEING MADE TO COMBAT ONE OF THE TWO RECALCITRANT CANCERS, PANCREATIC CANCER AND THE OTHER SMALL CELL LUNG CANCER. I'M SORRY I CAN'T BE THERE IN PERSON TO DO THIS. JUST A BRIEF OUTLINE, YOU HAVE A LITTLE BACKGROUND ALREADY ABOUT RECALCITRANT TUMOR ACT. WE WILL TALK BRIEFLY ABOUT THAT. JUST START OUT WITH PRIMER ON PAN CREE T CATTIC CANCER FOR PEOPLE WHO DON'T DEAL WITH THIS DISEASE DAY IN AND OUT. GO THROUGH A FEW VERY SELECTED SCIENTIFIC AND CLINICAL ADVANCES, HAPPY TO ADDRESS ANY QUESTIONS PEOPLE HAVE SPECIFIC AREAS OF RESEARCH THEY'RE INTERESTED IN HEARING MORE ABOUT. ONE SLIDE OUTLINING THE RECALCITRANT CANCER ACT AND WHAT IS REQUIRED OF THE NCI IN TERMS OF PRESENT INFORMATION BACK TO CONGRESS. THE MAJORITY OF THE TALK IS TALKING ABOUT THE PROGRESS DISCUSSION FROM THE PDAC WORKING GROUP. MOST HORIZON SCANNING SO THIS SORT OF HORIZON SCANNING EXERCISE TO TALK ABOUT WHERE SHOULD WE BE GOING FUTURE AND TRYING TO DRAW CONCLUSIONS, HAPPY TO TAKE SOME QUESTIONS AT THAT POINT. SO A FEW BASIC THINGS ABOUT PANCREATIC CANCER, YOU SAW FROM DR. SHARPLESS SOME DATA, PANCREATIC CANCER OF COURSE IS ONE OF THE MOST AGGRESSIVE AND LEAST TREATABLE AT THIS POINT OF ALL THE SOLID TUMORS. THANKFULLY IT ONLY MAKES UP 2% OF CANCER CASES BUT INCREASINGLY IT IS CAUSE OF CANCER RELATED DEATH. AROUND 5% AT THE PRESENT TIME BUT IT'S MOVING UP QUICKLY IN TERMS OF ITS FREQUENCY OF BEING CAUSE OF DEATH, PROJECTED THIS IS WORK DONE BY THE PANCREATIC CANCER ACTION NETWORK AND OTHER ADVOCACY GROUPS. PROJECTED TO BECOME THE SECOND LEADING CAUSE OF CANCER RELATED DEATH BY YEAR 2030. SO THIS DISEASE IS VERY DIFFICULT TO CURE. WE WILL TALK EFFORTS SCREENING EFFORTS, TRYING TO IDENTIFY PATIENTS VERY EARLY PANCREATIC CANCER WHERE SURGICAL INTERVENTION IS MORE SUCCESSFUL BUT IN GENERAL PATIENTS ABLE TO UNDERGO SUCCESSFUL SURGERY HAVE A CHANCE TO CURE. THE FIVE YEAR SURVIVAL TRENDS HAVE IMPROVED VERY SLIGHTLY FROM 1989 TO 2013. THAT'S ENCOURAGING. BUT IT'S STILL WAY UNDER WHERE WE NEED TO BE. CURRENTLY, 40% OF PATIENTS STILL PRESENT WITH METASTATIC DISEASE, 20% WITH EXTENSIVE VASCULAR INVOLVEMENT THEY FELT UNRESECTABLE USING CURRENT SURGICAL TECHNIQUES. THEN ABOUT 40% HAVE POTENTIAL TO UNDERGO SURGERY DEPENDING ON THE EXTENT OF THAT VASCULAR INVOLVEMENT. THESE TUMORS ARE KNOWN TO BE HIGH LIE RESISTANT TO THERAPY, YOU HEARD FROM DR. SHARPLESS IMMUNOTHERAPY HAS BEEN A REAL SUCCESS STORY IN OTHER DISEASE SETTINGS BUT HAVE NOT REALLY -- AT LEAST TO DATE FOR SOME OF THE AVAILABLE CHECK POINT INHIBITORS AND OTHER STRATEGIES, BEEN VERY RESPONSIVE TO IMMUNOTHERAPY. THERE'S A LOT OF WORK BEING DONE NOW TO TRY TO UNDERSTAND THAT PHENOMENA AND COUNTER ACT IT. UNFORTUNATELY ESPECIALLY FOR PATIENTS WITH METASTATIC DISEASE SURVIVAL IS MEASURED IN TERMS OF MONTHS. IN TERMS OF RISK FACTORS, THERE ARE A NUMBER AND BECOMING INCREASINGLY WELL DEFINED, PARTICULARLY THE GENETIC RISK FACTORS, BUT THERE ARE ENVIRONMENTAL FACTORS AS WELL, CIGARETTE SMOKING CONTINUES TO BE A SIGNIFICANT PROBLEM. PATIENTS WITH CHRONIC PANCREATITIS OF ANY ETIOLOGY, ALCOHOL, GENETIC, AND OTHER CHRONIC PANCREATITISIES PATIENTS AFTER TEN YEARS ARE HIGHER RISK FOR PANCREATIC CANCER. IN THE LAST FIVE TO SIX YEARS OBESITY IS A SIGNIFICANT RISK FACTOR FOR PANCREATIC CANCER WORKING OUT MECHANISMS FOR THAT IS WORK ONGOING. RELATIONSHIP WITH DIABETES IS COMPLEX AND WE'LL TALK ABOUT THAT BUT IMPORTANT TO RECOGNIZE DIABETES CAN BE CAUSED BY CANCER -- BUT MINOR RISK FACTOR FOR THE DISEASE. GENETIC UNDERSTANDING OF GERM LINE ALTERATIONS THAT CAN INCREASE RISK FOR PANCREATIC CANCER IS WELL KNOWN AT THIS POINT IN TIME, ACTUALLY FACTORED INTO MANAGEMENT OF PATIENTS WITH PANCREATIC CANCER INCREASINGLY. CERTAIN HEREDITARY SYNDROMES, THE CLASSIC WOULD BE BRCA 1 AND 2 PATIENTS BUT THERE ARE OTHERS THAT HERE CD K ANDEN 2A MUTATIONS AND OTHERS AS WELL T. OTHER NEOPLASMS ARE MUCIN ASISSIC PATTERNS CT SCANS PERFORMED FOR OTHER REASONS THAT INCREASE THE RISK OF PANCREATIC CANCER AND UNDERSTANDING THE NATURAL HISTORY AND UNDERLYING BIOLOGY OF THESE LESIONS IS AN AREA OF ACTIVE RESEARCH. AS YOU SAW, FUNDING FOR PANCREATIC CANCER HAS PARALLELLED THE INCREASED FUNDING OVERALL FOR THE NCI. THIS SHOWS AFTER A LITTLE LAG TIME FROM 2012 WHICH IS PASSAGE OF RECALCITRANT CANCER ACT, SHORT LAG TO GET ORGANIZED AND DEVELOP THE FRAMEWORK FOR WHAT WAS GOING TO BE DONE AND ADDRESSED IN PANCREATIC CANCER AND FUNDING HAS GENERALLY GONE UP SINCE THAT TIME. SO JUST A COUPLE OF SCIENTIFIC ACCOMPLISHMENTS, THESE ARE VERY SELECTED BOTH THESE IN THE CLINICAL ACCOMPLISHMENTS AND PEOPLE HAVE OTHER SPECIFIC THINGS THEY WANT TO TALK ABOUT, I'M HAPPY TO TRY TO ADDRESS THEM. BUT WE HAVE SEEN IN THE PAST FIVE TO SIX, SEVEN YEARS, WE HAVE NOW A GENOMIC AS WELL AS TRANSCRIPTIONAL PROFILES OF PANCREATIC CANCER, THERE ARE A NUMBER OF PAPERS I HIGHLIGHTED ONE HERE FROM UNC, BASICALLY IDENTIFYING PROGNOSTIC SUBTYPES OF PANCREATIC CANCER BASED ON EXPRESSION PROFILES IN THE TUMOR AS WELL AS TUMOR RELATED STROMA, THIS IS AN IMPORTANT PAPER BECAUSE IT REALLY HELPS TO DISECT OUT THE CONTRIBUTION OF THE TUMOR RELATED STROMA IN TERMS OF NATURAL HISTORY OF BIOLOGY OF PANCREATIC CANCER. WE HAVE BETTER MODELS FOR PANCREATIC CANCER DEVELOPED BY PEOPLE LIKE TILER JACK, GENETICALLY ENGINEERED MOUSE MODEL OF THE DISEASE, A LARGE NUMBER OF PATIENT DERIVED XENOGRAPH INCLUDING SUBSTANTIAL NUMBER THAT THE GROUP HEADED UP BY JIM DOROSHOW DEVELOPED PDXs THAT ARE WIDELY AVAILABLE FOR INVESTIGATORS AND INCREASINGLY ORGANOIDS ARE NOW BEING DEVELOPED FROM PANCREATIC CANCER AND BEING DEPLOYED FOR HIGH THROUGH PUT DRUG TESTING AND OTHER STRATEGIES. I MENTION TUMOR RELATED STROMA, THIS IS A PROMINENT COMPONENT OF THE PATHOLOGY OF PANCREATIC CANCER AND UNDERSTANDING THE CROSS TALK BETWEEN STROMA AND PANCREATIC CANCER CELLS IS CRITICAL AND PROBABLY IS GOING TO NEED TO BE UNDERSTOOD AT DEEP LEVEL TO REALLY MAKE IMMUNOTHERAPY A RATIONAL APPROACH FOR PANCREATIC CANCER PATIENTS. AND WORK IS ONGOING IN MANY LABORATORIES TRYING TO DO THIS. I MENTION RELATIONSHIP BETWEEN DIABETES AND OBESITY OF PANCREATIC CANCER AND CLEARLY THERE'S -- WE WILL TALK ABOUT RESEARCH ONGOING AND LOTS OF INTEGRATION BETWEEN NCI AND NIDDK TO REALLY UNDERSTAND ESPECIALLY THE RELATIONSHIP OF DIABETES AND THE POSSIBILITY OF IDENTIFYING NEW ONSET DIABETICS THAT MAY HARBOR VERY EARLY PANCREATIC CANCER. SO THIS MECHANISTIC UNDERSTANDING OF THESE TWO METABOLIC ALTERATIONS THAT ARE FREQUENTLY SEEN IN PANCREATIC CANCER IS A MAJOR FOCUS OF CURRENT EFFORTS AT NCI AND ACROSS THE NIH. I WANT TO SHOW A COUPLE OF DATA SLIDES. THIS IS A PAPER A. DRAW YOUR ATTENTION TO PANEL B HERE, THE MOFFET PAPER I MENTION LOOKING AT PANCREATIC CANCER SUBTYPES BASED ON EXPRESSION PROFILING AND VERY NICE PAPER, IT'S A LARGE COLLABORATION ACROSS MANY DIFFERENT CENTERS TO ACQUIRE ENOUGH SAMPLES TO TEST. BUT IT SHOWS PANEEIUS CANCER IS NOT A MONOLITHIC DISEASE, IT HAS SUBCLASSIFICATIONS WE ARE LEARNING ABOUT, THEY TOO WITH RESPECT TO TUMOR CELLS BASAL VERSUS CLASSICAL ALTERATIONS. THIS PAPER IS NICE I THINK IN THE WAY IT'S INTEGRATED AND UNDERSTANDING OF THE TUMOR RELATED STROMA AND IS CHARACTERIZED BOTH ACTIVATED AS NORMAL STROMA AND IT'S IMPACT ON PROGNOSIS. THE CHALLENGE IS TO TAKE THIS INFORMATION AND TRANSFER INTO THERAPEUTIC OPPORTUNITIES AND ALSO CAN WE DEVELOP SIMPLIFIED TESTS SUCH AS IMMUNOHISTOCHEMICAL STUDIES PATHOLOGISTS CAN USE TO FEED THAT INFORMATION IMMEDIATELY BACK TO THE CLINICIAN. MANAGING THE PATIENT. THAT'S WORK ONGOING. WITH RESPECT TO CLINICAL ADVANCEMENT, THERE'S BEEN A SERIES OF TRIALS NOW LED BY INVESTIGATORS AT JOHNS HOPKINS, MIMI CANTO AND MIKE GOGGIS AND OTHERS THAT WORKED IN THIS AREA A LONG TIME AND DEMONSTRATEDED THAT IT IS POSSIBLE TO DO SUCCESSFULLY SCREEN PATIENTS FOR HIGH RISK PATIENTS FOR EARLY PANCREATIC CANCER, ONE OPERATES ON SUCH PATIENTS AT EARLY TIME POINT BEFORE DEVELOPMENT OF INVASIVE DISEASE APPEARS THOSE PATIENTS CAN BE CURED. EVEN THOSE PATIENTS WITH EARLY INVASIVE CANCER SURVIVAL TIME OVERALL SURVIVAL TIME IS EXTENDED. WHETHER THAT'S LEAD TIME BY STATISTICAL ISSUE REMAINS TO BE SEEN. IT'S POSSIBLE TO IDENTIFY CURRENT TECHNIQUE OF PATIENTS AT HIGH RISK WITH EARLY DISEASE AND INTERVENE IN THE APPROPRIATE SETTING. I MENTIONED UNDERSTANDING NEOPLASMS, WE ARE SEEING MORE OF THESE, THERE ARE SURGICAL CRITERIA DEVELOPED FOR WHEN ONE OPERATES ON THESE PATIENTS. LEARNING MORE NATURAL HISTORY AND TRYING TO IDENTIFY WHICH OF THESE LESIONS ARE HIGHEST RISK FOR INRAYSIVE CANCER IS STILL WORK IN PROGRESS. NEXT GENERATION SEQUENCING IS INCREASINGLY IN PANCREATIC CANCER AND WE IDENTIFY SUBSETS OF PATIENTS WITH PANCREATIC CANCER THAT ARE PARTICULARLY RESPONSIVE TO CLASSICAL CHEMOTHERAPY, CHEMOTHERAPEUTIC AGENTS LIKE CISPLATIN. THESE ARE PATIENTS WITH HOMOLOGOUS RECOMBINATION REPAIR DEFECTS, ALTERATIONS IN BRC 1 AND BRCA 2 ET CETERA. ALSO ONE MORE DATA SLIDE IN SECOND. SOME LIMITED INFORMATION ABOUT VERY SPECIFIC TARGETED THERAPIES THAT MAYBE AD VAN STAY YOUS TO SMALL SUBSETS OF PATIENTS WITH PANCREATIC CANCER, WORK IS UNDERWAY AND HOPEFULLY WE'LL BE ABLE TO EXPAND HE NUMBER OF TARGETED AGENTS THAT ARE APPLICABLE TO PATIENTS WITH PANCREAS CANCER IN THE FUTURE. WE HAD A COUPLE OF APPROVALS, PACK LA TACK SOL GOES BACK A LITTLE WAYS AND -- WE ARE IN THE ERA OF CYTOTOXICS, AT LEAST CURRENTLY FOR THIS DISEASE. WE NOW HAVE HIGH LEVEL DATA TO SUGGEST THAT CHEMOTHERAPY AFTER SURGERY WITH COMBINATION -- CAN SIGNIFICANTLY INCREASE THE SURVIVAL OF PATIENTS WHO HAVE UNDERGONE SUCCESSFUL SURGICAL OPERATIONS AND RECOVER FAST ENOUGH TO BE ABLE TO RECEIVER CHEMOTHERAPY. WHAT MAYBE LESS WELL RECOGNIZED BUT IS NONETHELESS VERY IMPORTANT IS INTEGRATING OUR CURRENT MODALITIES AND UTILIZING NEOADJUVANT APPROACH TOES THIS DISEASE AS WELL AS ADJUVANT THERAPIES HAS BEEN THE DRIVER TO IMPROVE SURVIVAL STATISTICS YOU SAW, SLIGHT INCREASE IN OVERALL SURVIVAL TO THE 8 TO 9% RATE. SO WE ARE BETTER ABLE TO INTEGRATE MODALITIES AND IMPROVED WAYS TO MANAGE CONSTRUCTIVE COMPLICATIONS THAT CAN BE DEVASTATING FOR PATIENTS WITH PANCREATIC CANCER WITH MODERN ENDOSCOPIC TECHNIQUES. THIS IS JUST DATA TRILLION PAN CAN KNOW YOUR TUMOR PROGRAM. IT DOES SUGGEST THAT IN A SUBSET OF PATIENTS A SMALL SUBSET OF PATIENTS, IT VERY AD WITH A TOTAL PATIENT -- STARTED WITH A TOTAL POPULATION OF -- ABOUT 20% HAD THE INVESTIGATORS USE OR THE TREATING PHYSICIANS USE THE INFORMATION FROM THEIR PROFILING TO DESIGN THEIR THERAPEUTIC APPROACH BUT IF ONE HAD HIGHLY ACTIONAL WITH THERAPEUTIC IS IT POSSIBLE TO IMPROVE THE OUTCOME FOR THESE PATIENTS SO THIS IS WORK REALLY GETTING STARTING AND NEEDS TO BE EXPAND IN THE FUTURE. PAT HAS TALKED ABOUT THIS SO I WON'T BELABOR THIS BUT THIS IS THE REQUIREMENT STIPULATED BY RECALCITRANT CANCER RESEARCH ACT OF 2012. WE ARE AT THIS FIVE YEAR UPDATE PERIOD NOW, IN BLUE HERE WHERE WE ARE DEVELOPING -- HELPING NCI DEVELOP SCIENTIFIC FRAMEWORK THAT WILL GO TO CONGRESS IN 2019. SO THIS IS BASICALLY THE FOUR PROPOSED SCIENTIFIC INITIATIVES FROM THE ORIGINAL HORIZON SCANNING WORK AND PSYCHOFRAMEWORK PUT TOGETHER BY THE NCI -- SCIENTIFIC FRAMEWORK PUT TOGETHER BY THE NCI AND THESE FOUR INITIATIVES PROPOSED DEVELOP IN DEPTH UNDERSTANDING OF RELATIONSHIP BETWEEN PANCREATIC CANCER AND DIABETES MELITIS ONSET, EVALUATE SCREENING PROTOCOLS FOR BIOMARKERS FOR EARLY DETECTION OF PANCREATIC CANCER BUT MORE GENERAL PATIENTS AS WELL AS PATIENTS AT KNOWN HIGHER RISK FOR DEVELOPING DISEASE. AT THAT TIME THERE WAS CERTAINLY INCREASE INTEREST IN DEVELOPING APPROACHES TO IMMUNOTHERAPY THAT CONTINUES TODAY. THIS WAS THE POINT IN TIME AT WHICH THE RAS INITIATIVE BASED OUT AT THE FREDERICK LABORATORIES HEADED BY FRANK MCCORMICK GOT THEIR START AND WAS A KEY INITIATIVE BACK IN 23014. SO WE BASICALLY OUR WORK WE CONVENED I GUESS THIS WAS DONE UNDER VERY RAPID TIME FRAME, TO THE CREDIT OF PEOPLE INVOLVED IN THIS, SHEILA PRINDIVILLE AND OTHERS, DEBBIE JAFFE KEPT US MOVING ALONG, TRY TO PROVIDE UPDATE KEY SCIENTIFIC ADVANCES ASSESS PREVIOUS INITIATIVES. IDENTIFY WHETHER THEY FELT IT SCIENTIFICALLY RELEVANT AND HOW THEY NEED TO BE MODIFIED. AND I TALKED A LITTLE BIT DO WE FEEL NCI IS ON TRACK IN TERMS OF CORRECT RESEARCH DIRECTION AND AGAIN AS TYPICAL FOR THE WORKING GROUPS I HAVE BEEN INVOLVED WITH NCI, THERE'S A LOT OF GROUND WORK TO PROVIDE PORTFOLIO ANALYSIS AND OUTLINE AVAILABILITY AND WHAT'S DONE IN THE CLINICAL TRIALS ARENA TO PROVIDE INFORMATION FOR THE COMMITTEE TO REVIEW. THIS REPORT WILL BE DUE -- THE NEW SCIENTIFIC FRAMEWORK WILL BE DUE CONGRESS IN MARCH OF 2019. SO THIS WAS LED BY TONY HOLINGS WORTH AND MYSELF WE DIVIDED THE WORK INTO FOUR AREAS YOU SEE HERE, AND BIOLOGY WHICH ENCOMPASS GENOMICS AND METABALOMICS AND TUMOR BIOLOGY LED BY TONY. ANIMAL HUMAN TISSUE MODELING, LED BY DAVID TUGESON RISK PREVENTION SCREENING AN DIAGNOSE MOWSIS LED BY ALLISON KLINE FROM JOHNS HOPKINS AND I OVERSAW THE TREATMENT SUBCOMMITTEE, SUBGROUP. THIS WAS THE ORGANIZATION OF OUR WORKING GROUP MEETING. WE HAD GREAT UPDATES FROM THE NCI, NIH. BASICALLY UPDATING COMMITTEE ON STATUS OF BIOMARKERS EARLY DETECTION AND SCREENING FROM DANA ANDERSON FROM NIDDK, UPDATED THE COMMITTEE ON THE CONSORTIUM FOR PANCREATITIS, DIABETES AND CANCER, PETER GAVE A BRIEF UPDATE OF THE MOON SHOT INITIATIVES WHICH IS WHERE IMMUNOTHERAPY AND MICROENVIRONMENT IS INCORPORATED AND DWIGHT TALKED ABOUT THE STATUS OF THE RAS INITIATIVES. THE OTHER SESSIONS WERE BASICALLY REPORT OUTS FROM THE FOR AREAS OF WORK THAT I JUST DESCRIBED AND A BRIEF GENERAL DISCUSSION WITH SOME FINAL CONCLUSIONS. JUST TO GO BACK IN TERMS OF PROGRESS IN THE SCIENTIFIC INITIATIVES, I HAVE BROKEN THIS UP TO THREE, TWO FIT TOGETHER IN THE EARLY DETECTION RISK SCREENING. STRATEGIES THAT HAVE BEEN ADDRESSED OVER THE PAST FIVE YEARS. JUST VERY HIGH LEVEL, THIS HAS BEEN A COLLABORATIVE EFFORT WITH LOTS OF PEOPLE AT THE NCI AS WELL AS OTHER INSTITUTES PARTICULARLY THE NIDDK. SO WE HAVE ENGAGED THE EDRN IN PROGNOSTIC BIOMARKERS. CONSORTIUM OF CBD PC FOR CHRONIC PANCREATITIS DIABETES AND PANCREATIC CANCER IS WELL UP AND RUNNING AND THEY HAVE A NUMBER OF WORKING GROUPS LOOKING AT THE DIABETES PANCREATIC CANCER, RELATIONSHIP TRYING TO IDENTIFY BIOMARKERS FOR IDENTIFYING THOSE SUBSETS OF PATIENTS WITH NEW ONSET WITH DIABETES THAT HARBOR PANCREATIC CANCER, THERE IS A GROUP WORKING SPECIFICALLY ON TYPE 3 DIABETES MELITIS, TYPE OF DIABETES THAT IS ASSOCIATED WITH PANCREATIC CANCER TRYING TO UNDERSTAND THE BIOLOGY AND ENDOCRINOLOGY AROUND THAT. AND TWO WORKING GROUPS WORKING ON CHRONIC PANEEIATITIS. ONE IS ADULT PANCREATITIS AND ONE ON THE PEDIATRIC SIDE. WITH RESPECT TO IMMUNOTHERAPY AND MICROENVIRONMENT, THERE IS A CONSORTIUM FOR MOLECULAR CHARACTERIZATIONS KOREAN DETECTED LESIONS -- SCREEN DETECTED LEAGUES THAT IS UP AND RUNNING AND WORKING AT THIS POINT. FROMWITH RESPECT TO IMMUNOTHERAPY THE WORK IN PANCREATIC CANCER IS EMBEDDED IN THE MOON SHOT INITIATIVE, THERE IS A OVER TWO YEARS NCI DEVELOPED PANCREATIC CANCER MICROENVIRONMENT NETWORK. THE GOALS OF THE NETWORK ARE AS OUTLINED HERE, TO UNDERSTAND THE MICROENVIRONMENT AND ITS CELLULAR HETEROGENEITY AT A DEEPER LEVEL, UNDERSTAND WHAT MAKES THE MICROENVIRONMENT PANCREATIC CANCER AN IMMUNE AS WELL AS DRUG PRIVILEGED MICROENVIRONMENT. UNDERSTAND MORE ABOUT THE CELLULAR CROSS TALK BETWEEN PANCREATIC CANCER CELLS AND ACTIVATED CELLS AS WELL AS OTHER CELLS THAT MAKE UP THE MICROENVIRONMENT AND THEN LOOKING AT WAYS OF REPROGRAMMING THE MICROENVIRONMENT TOWARD IMMUNORESPONSIVENESS. WITH RESPECT TO THE RAS INITIATIVE, THERE'S TWO MAJOR COMPONENTS TO THIS, THIS WAS RECENTLY REVIEWED, UNDERWENT EXTERNAL REVIEW AND WAS REFUNDED. BUT BASICALLY, THERE'S TWO APPROACHES BEING LOOKED AT AND I PUT K IN PARENTHESIS HERE BECAUSE THIS IS NOT JUST A KRISTIN RAS INITIATIVE, IT'S A RAS INITIATIVE SO RELEVANT TO PANCREATIC CANCER. BUT IT IS A LITTLE BIT BROADER THAN JUST KRISTIN RAS. BASICALLY TRYING TO DEVELOP KRAS TARGETED THERAPIES AS WELL AS EXTENDING LE TALLTY APPROACHES THAT HAVE BEEN TRIED WITH OTHER LABORATORIES AND PUBLISHED VARIOUS POINTS IN TIME. BUT TAKING ANOTHER LOOK MORE COMPREHENSIVELY SYNTHETIC LETHALITY AS AN APPROACH TO TARGET KRAS. GIVEN THE FACT THE PROTEIN ITSELF IS SO CHALLENGING TO TARGET WITH SMALL MOLECULES. JUST THE ACTUAL WORK PRODUCT OF THE WORKING GROUP MEETING FOCUSED ON WHAT IS COMING UP ON HORIZON AND WHERE ARE THE OPPORTUNITIES IN PANCREATIC CANCER. WE THOUGHT THIS WOULD BE THE MOST USEFUL INFORMATION TO TRY TO FEEDBACK TO NCI. AS THEY DEVELOP THEIR SCIENTIFIC FRAMEWORK. SO TUMOR BIOLOGY WE NEED DEEPER MORE CONTINUED UNDERSTANDING OF THE MICROENVIRONMENT AS IT CONTRIBUTES TO DRUG RESISTANCE AND IMMUNOSUPPRESSION. THERE'S LOTS OF NEW DATA ABOUT BIOMECHANICAL AND BIOPHYSICAL PROPERTIES OF THE STROMA THAT MAY RELATE TO ITS RESISTANCE, AND UNDERSTANDING BASIC MECHANISMS OF METASTASIS. SPRINKLED THROUGHOUT THE PRESENTATION AN EMPHASIS ON MORE IMAGING STRATEGIES, MORE SOPHISTICATED IMAGING FOR EARLY DETECTION AND TO UNDERSTAND RESPONSIVENESS OR LACK OF RESPONSIVENESS TO THERAPEUTIC INTERVENTION. THE KRAS PROGRAM WE FEEL IS -- NEEDS TO CONTINUE AND TO TRY TO IDENTIFY SPECIFIC TARGETED AGENTS OR OTHER APPROACHES TO INTERFERE WITH R ASHESS SIGNALING. THERE ARE PHARMA COLLABORATIONS, THOSE MIGHT BE EXTENDED IN THE FUTURE AS BASIC INFORMATION FROM THE INITIATIVE CAN BE TRANSLATED INTO THE CLINIC. PANCREATIC CANCER IS A DISEASE ASSOCIATED WITH SYSTEMIC AND LOCAL METABOLIC PERTURBATIONS, KRAS ITSELF CREATES TREMENDOUS ALTERATIONS IN CELLULAR METABOLISM OF GLUCOSE AND GLUTAMINE AND ALTERS WAY ENERGY THE CELL DERIVES ENERGY FROM VARIOUS METABOLIC PRODUCTS. WE NEED TO UNDERSTAND THAT FURTHER AND WE NEED TO BE ABLE TO USE THAT INFORMATION TO POTENTIALLY TARGET THE DISEASE. SYSTEMICALLY THIS IS A DISEASE CHARACTERIZED BY TREMENDOUS WASTING BOTH FAT AND MUSCLE AND WE ARE JUST AT THE BEGINNING TO UNDERSTAND THE PATHOPHYSIOLOGY OF THAT PROCESS. TO THIS COULD HAVE SIGNIFICANT IMPLICATIONSES FOR PATIENTS UNDER ACTIVE TREATMENT AS THEY SEEM TO CONTINUE TO LOSE WEIGHT EVEN IN THE CONTEXT OF WHAT APPEARS TO BE RESPONDING DISEASE. THE MICROBIOME IS RELATIVELY UNEXPLORED IN ITS RELATIONSHIP TO PANCREATIC CANCER AND NEEDS TO BE EMPHASIZED. THROUGHOUT THESE DISCUSSION THERE IS RECK ANYTHING AT EVERY LEVEL WE NEED TO BE ABLE TO INTEGRATE MORE CORRELATIVE SCIENCE INTO THE CLINICAL TRIALS TO GIVE EARLIER INDICATIONS TO WHAT'S WORKING AND WHAT IS NOT AND MECHANISTICALLY TO DERIVE INFORMATION FROM EACH OF THE TRIALS WE DO. WITH RESPECT TO ANIMAL MODEL SYSTEMS THIS IS AN AREA THAT HAS COME A LONG WAY, GENETICALLY ENGINEERED MOUSE MODELS THAT LED THE WAY TO LOTS OF I THINK USEFUL INFORMATION ABOUT BIOLOGY AND EVEN HELP IDENTIFY POTENTIAL NEW THERAPIES. MODELS CAN BE IMPROVED. AS YOU PROBABLY KNOW, THE WAY THESE MODELS ARE GENERATED CURRENTLY, USING DEVELOPMENTAL PROMOTER WHICH KRAS IS EXPRESSED IN ALL CELLS OF DEVELOPING PANCREAS. THAT IS NOT THE WAY CANCER DEVELOPED IN PEOPLE SO REFINE MODEL TO OVEREXPRESS OR E PRESS KRAS IN SPECIFIC CELLULAR COMPONENTS, OR DUCTILE CELLS IS WORK THAT IS ONGOING AND NEEDS TO CONTINUE. PLUS WE NEED TO UNDERSTAND HOW METABOLIC INSULT SUCH AS PANCREATITIS, DIABETES AND OBESITY, FACTOR INTO PATHOPHYSIOLOGY OR PATHOGENESIS OF PANCREATIC CANCER. CONTINUED STUDY OF HIGH RISK PRECURSORS LESIONS AND IPMN, BETTER MODELS FOR METASTASIS AS WELL AS CACHEXIA AND SARCOPENIA. MODELS THAT HELP US FACILITATE THE STUDIES OF IMMUNOTHERAPY, RIGHT NOW THE AVAILABLE MODELS ARE NOT EFFECTIVE IN THAT CONTEXT. AND AGAIN, USING MORE SOPHISTICATED IMAGING, TO ASSESS IMPACT OF THERAPEUTIC INTERVENTION OR HELP DETECT EARLIER LESIONS CAN BE ASSESSED IN BETTER -- IN THESE BETTER MODELS. THEN THE MODELS NEED TO BE ABLE TO INCORPORATE WHAT I DESCRIBE TO YOU AS THE INTERACTION BETWEEN CANCER CELLS AND STROMA, WE DO NOT HAVE MODELS THAT DO THAT VERY EFFECTIVELY AT THIS POINT IN TIME. WITH RESPECT TO RISK PREVENTION SCREENING AND DIAGNOSIS, THE WORK ON PANCREATIC CANCER AND DIABETES MELITIS IS WELL UNDERWAY. I THINK THERE'S GOING TO BE SOME REALLY USEFUL INFORMATION THAT'S GOING TO COME OUT OF THAT. WE NEED TO UNDERSTAND THE ROLE OF GLUCOSE INTOLERANCE THAT MAY EXIST IN A WELL BEFORE DIAGNOSED WITH DIABETES, IS THAT A BETTER WINDOW, INCIDENCE TO EARLY PANCREATIC CANCER THAN WAITING FOR PATIENTS TO DEVELOP DIABETES. THE RELATIONSHIP BETWEEN DIABETES AND PANCREATIC CANCER IMPLIES THERE'S A STRONG ROLE FOR INSULIN IN THE PATHOPHYSIOLOGY, THAT NEEDS TO BE UNDERSTOOD AT A DEEPER LEVEL. WE NEED TO LOOK AT THE MECHANISM OF INCREASE RISK CONFIRMED BY OBESITY AND UNDERSTAND THAT, CONTINUE TO UNDERSTAND NATURAL HISTORY OF IPMN AND THE MUCIN CYSTIC NEOPLASM OF THE PANEE WAS, FOCUSING SOME OF -- PANCREAS FOCUSING EFFORTS ON SOME OF THE IMAGING. CONTINUED RESEARCH TO HERITABLE CAUSES OF PANCREATIC CANCER, WORK IS NOW OCCURRING IN CANCER GRANT AND IN OTHER CONTEXT TO EXPAND GERM LINE TESTING OF PATIENTS NEWLY DIAGNOSED WITH PANCREATIC CANCER AND BEGIN TO THE PROCESS OF WORKING ON CASCADE TESTING IN TO PATIENTS AND FAMILIES. THIS IS STIMULATED PARTLY BY RECOGNITION FAMILY HISTORY ITSELF IS NOT A PREDICTOR OF SUBSET, SMALL, YET IMPORTANT SUBSET OF PATIENTS WITH GENETIC PREDISPOSITION FOR PANCREATIC CANCER THAT WE'RE JUST NOT GOING TO PICK UP BY TYPICAL TAKING A TYPICAL FAMILY HISTORY. THE DATA GENERATED TO DATE, ALL THE WORK I MENTIONED ABOUT PACK CREE CATTIC CANCER SUBTYPES, WORK OF THE TCGA AND CONSORTIA ALL DONE HARMLY IN CAUCASIAN PATIENTS. WE NEED TO UNDERSTAND -- LARGELY IN CAUCASIAN PATIENTS. WE NEED TO UNDERSTAND WE NEED GREATER MINORITY REPRESENTATION IN STUDIES OF PANCREATIC CANCER. WE KNOW LIMITED DATA THAT EVEN IF THE LEVEL OF KRAS MUTATION, SPECIFIC ALTERATION IN KRAS AND AFRICAN AMERICAN LOOKS TO BE DIFFERENT THAN THAT IN CAUCASIAN PATIENT WHERE AFRICAN AMERICAN PATIENTS CODON 12 ALTERATION IS A G 12B ALTERATION, IN CAUCASIAN IT'S TYPICALLY A G 12D ALTERATION. THAT'S JUST VERY LIMITED DATA BUT I THINK JUST SUGGESTS THAT WE DON'T REALLY UNDERSTAND THIS DISEASE IN NON-CAUCASIAN POPULATION. THEN CONTINUING TO BROADEN OUR EFFORTS EARLY DETECTION IN THESE HIGH RISK AND EVEN AVERAGE RISK PATIENTS THROUGH BETTER DEVELOPMENT OF BETTER BIOMARKERS AND SCREENING METHODS. FINALLY WITH TREATMENT, CONTINUING THE RAS EFFORTS, CONTINUING THE PRECISION MEDICINE EFFORTS, ONE BIG LIMITATION IN TERMS OF PRECISION MEDICINE IS THE TURNAROUND TIME FOR NEXT GENERATION SEQUENCING. THAT HAS TO BE IMPROVED STREAMLINED IF WE'RE GOING TO BE ABLE TO REALLY APPLY SPECIFIC PRECISION APPROACHES TO FIRST LINE MANAGEMENT OF PATIENTS WITH PANCREATIC CANCER. MANY PATIENTS IF THEY PROGRESS BEYOND FIRST LINE CYTOTOXIC THERAPY ARE NOT NECESSARILY ABLE PHYSICALLY TO SECOND SECOND OR THIRD LINE THERAPY. SO WE HAVE TO FIGURE HOW TO TURN THAT INFORMATION AROUND MUCH MORE QUICKLY. I MENTIONED SARCOPENIA AND CACHEXIA. THESE ARE IMPORTANT PROBLEMS CREATED BY PANCREATIC CANCER, WE NEED TO UNDERSTAND BETTER AND FIGURE BETTER WAYS TO INTERVENE. IMPROVING TISSUE ACQUISITION METHODOLOGIES TO CONDUCT HIGH QUALITY CORRELATIVE SCIENCE WITHIN CLINICAL TRIALS. THIS IS MAJOR FOCUS I KNOW OF THE ETCTN. I'M INVOLVED WITH THAT GROUP. THEY HAVE DONE A LOT OF WORK AND JEFF AND COLLEAGUES, JEFF ABRAMS AND COLLEAGUES DESERVE A LOT OF CREDIT FOR TRYING TO STANDARDIZE THESE APPROACHES TO REALLY GET HIGH QUALITY CORRELATIVE SCIENCE DONE. IT'S A PARTICULAR CHALLENGE IN PANCREATIC CANCER AND WE NEED TO WORK ON THAT. INCREASING ACCESS TO PATIENT TRIALS, PARTICULARLY MINORITY POPULATIONS. AS WE GAIN MORE UNDERSTANDING OF THE IMMUNOSUPPRESSIVE MICROENVIRONMENT, I THINK THIS IS GOING TO LEAD TO NOVEL IMMUNOTHERAPY STRATEGIES THAT WE NEED TO RAPIDLY TRANSLATE INTO THE CLINIC. THIS DISEASE I TRY TO SHOW YOU IN A SIMPLISTIC LEVEL THROUGH EXPRESSION PROFILING, IT IS A VERY HETEROGENEOUS DISEASE. AND WE NEED TO DIG DEEP AND UNDERSTAND THE EXTENT OF THE HETEROGENEITY IN ORDER TO POTENTIALLY USE THAT INFORMATION, FOR SCREENING BUT STRATIFICATION FOR PATIENTS IN CLINICAL TRIALS AND APPLICATION OF SPECIFIC THERAPIES TO THOSE INDIVIDUALS. THE OVERALL -- >> JIM, IF YOU CAN WRAP UP QUICKER BECAUSE WE WANT TIME FOR SOME QUESTIONS. >> WE'RE DONE. JUST ABOUT DONE. WE CAN JUST STOP WITH THIS SLIDE. SO BASICALLY WE FEEL THERE HAVE BEEN ADVANCES, SOME PROGRESS, RECALCITRANT TUMOR ACT ESSENTIALLY IS FIVE YEARS OLD, BEEN A LOT OF WORK PUT INTO PLAY, PARTICULARLY PREVENTION SCREENING UNDERSTANDING RELATIONSHIP WITH DIABETES. THE SENSE OF THE COMMITTEE IS NCI IS RESPONSIVE TO THE RESEARCH DIRECTION. OUTLINED BY THE 2014 SCIENTIFIC FRAMEWORK. THE FRAMEWORK IS RELEVANT. THE QUESTIONS THAT HAVE BEEN RAISED THERE IN -- AND THE APPROACHES THAT NEED TO BE TAKEN ARE STILL BASICALLY UNDERWAY. FOR THAT REASON HAVEN'T BEEN FULLY COMPLETED, NEED TO BE UPDATED, PROBABLY NEED TO BE -- THERE NEEDS TO BE CONSIDERATION FOR REFUNDING ESPECIALLY FOR SOME OF THE LARGE CONSORTIA JUST GETTING UP AND RUNNING. AND THEN WE HOPE THAT THE WORK OF THE WORKING GROUP AND THE WAY WE HAVE OUTLINED THINGS WILL HELP TO IDENTIFY ADDITIONAL SCIENTIFIC OPPORTUNITIES THAT CAN BE PRIORITIZED AND TARGETED. SO I'LL STOP THERE AND HAPPY TO TAKE QUESTIONS THAT PEOPLE MIGHT HAVE. >> THANK YOU, JIM, INCREDIBLY THOROUGH. BEFORE WE OPEN UP, I THINK LYNN AND GLORIA YOU WERE ON THIS WORKING GROUP AND DAVE AND JIM WAS PRESENT SO IF YOU WANT TO OPEN WITH COMMENTS? >> FIRST, THANK YOU, JIM FOR THAT VERY NICE SUMMARY OF THE FIELD AS WELL AS WHAT THE WORKING GROUP HAS DONE THUS FAR. I THINK THE COMMITTEE VERY MUCH COMMENDS THE NCI FOR TAKING THIS VERY SERIOUSLY FOR LOOKING AT THOSE FOUR RESEARCH INITIATIVES THAT WERE IN THE SCIENTIFIC FRAMEWORK AND REALLY PUTTING EFFORTS INTO TRYING TO UNDERSTAND THOSE QUESTIONS AND REALLY GET RESEARCH GROUPS AROUND THOSE SPECIFIC ISSUES. I THINK IT COMES DOWN TO YOUR LAST SENTENCE THERE, THE LAST BULLET THAT THEY'RE NOT COMPLETED, THEY NEED TO BE UPDATED AND THERE ARE ADDITIONAL SCIENTIFIC OPPORTUNITIES THAT NEED TO BE PRIORITIZED AND TARGETED. SO THERE'S A LOT OF INFORMATION IN THESE SLIDES FROM THOSE FOUR WORKING GROUPS BUT I DON'T THINK THE COMMITTEE IS QUITE GOT TON THE POINT YET WHERE WE HAVE BEEN ABLE TO PRIORITIZE THEM AND FIGURE OUT WHAT ARE THOSE ISSUES THAT RISE TO THE TOP THAT ARE REALLY WHERE THIS GROUP WHICH HAS A LOT OF EXPERTISE IN PANCREATIC CANCER SEES THOSE OPPORTUNITIES TO GO FORWARD. SO I THINK WE HAD A LOT OF DISCUSSION FOR INSTANCE ABOUT METABOLISM THAT IS NOT JUST THE INTERACTION OF DIABETES BUT IT'S REALLY A MUCH BROADER METABOLIC SYNDROME. SO DOES THE INITIATIVE COVER THAT OR IS THAT NEED TO BE EXPANDED REALLY SUBSTANTIALLY GOING FORWARD, A LOT OF DISCUSSION ABOUT CLINICAL TRIALS. AND BACK TO WHAT'S THE DESIGN OF THOSE TRIALS AND WHAT'S THE ANALYSIS, IS IT DIFFERENT IN PANCREATIC CANCER THAN IN OTHER CANCERS? SO AGAIN USING THE EXPERTISE OF THIS GROUP TO THINK A LITTLE MORE DEEPLY ABOUT SOME OF THOSE QUESTIONS TO GUIDE FURTHER FUTURE EFFORTS NOT JUST SUMMARIZE WHAT WHAT HAPPENED SO FAR WHICH IS CERTAINLY SUBSTANTIAL BUT NEEDS TO GO FURTHER. >> I WOULD LIKE TO CONGRATULATE JIM ON A GREAT OVERVIEW OF THE REPORT TO SAY THAT I WAS INVOLVED IN THE -- ALONG WITH JIM AND OTHERS ON THIS REVIEW PANEL. IN THE 2014 FRAMEWORK. AND MY PERSPECTIVE IS THAT THERE HAS BEEN A LOT OF BANG FOR THE BUCK THAT'S COME OUT OF THE NCI INVESTMENT SINCE THAT FRAMEWORK WAS DEVELOPED AND I'M PLEASED WITH THE PROGRESS THAT HAS BEEN MANIFEST. I WANT TO ADD SOME INFORMATION TO COMPLIMENT WHAT JIM REPORTED. IN ADDITION TO THE VARIOUS CONSORTIA THAT FORMED AS A RESULT OF THE PANCREATIC CANCER INITIATIVES, THE SPORE PROGRAM AND THE -- THERE IS A NEW CONSORTIUM CALLED PANCREATIC CANCER DETECTION CONSORTIUM AND N CORPS HAVE PUT HANDS ON DECK ON THIS. THIS IS REALLY GOING TO WIDE NCI RESPONSE TO PANCREATIC CANCER FRAMEWORK. IT'S REALLY FANTASTIC TO SEE THE INVESTMENT PAYING OFF. I'M VERY HAPPY ABOUT THAT. I WANT TO ADD A COMMENT ABOUT THE RISK FROM A RISK AND EARLY DETECTION BECAUSE THAT'S WHERE I LIVE. THERE REALLY IS TREMENDOUS ADVANCES MADE IN THE GENETIC PRE-DISPOSITIONS AND UNDERSTANDING OF THE GENETICS OF PANCREATIC CANCER TO THE POINT WHERE PRACTICE CHANGE THAT HAS BEEN RECOMMENDED OR WILL BE COMING OUT VERY SOON FROM ONE PROFESSIONAL ORGANIZATION AND CERTAINLY THE NCCN RECOMMENDED THAT ALL PANCREATIC CANCER PATIENTS SHOULD HAVE PREDISPOSITION TESTING WHICH IS REMARKABLE WHEN ONLY 10% HAVE A POSITIVE FAMILY HISTORY. IT'S CLEAR THERE ARE LOTS OF PATIENTS WHO HAVE NO FAMILY HISTORY WHO HAVE A GENETIC PRE-DISPOSITIONS BUT UNDERSTANDING THAT IS A BLACK BOX IN MANY WAYS. THERE IS ACTUALLY WHAT IS HAPPENING AND WHAT IS GOING TO HAPPEN IS THERE'S GOING TO BE A NEW COHORT OF HIGH RISK PEOPLE IDENTIFIED AS A RESULT OF THIS GENETIC TESTING AND THAT'S FAMILY MEMBERS THAT WE HAVE NEVER DONE ANYTHING ABOUT. THEY'RE WORRIED, VERY WORRIED BUT THEY'RE NOW MAYBE TOOLS THAT ASSESSMENT OF THEIR RISK. THERE'S TWO OTHER IN ADDITION TO THE RECOMMENDATIONS FOR TESTING ALL PATIENTS, THERE'S ACTUALLY A NEW TREND OCCURRING ACROSS THE COUNTRY AND THAT'S DIRECT TO CONSUMER TESTING FOR CANCER GENES AND EMPLOYER TESTING FOR CANCER GENES. THERE'S ACTUALLY GOING TO BE ATING TO THIS COOR OF HIGH RISK PEOPLE THAT WE ARE NOT PREPARED TO DEAL WITH. -- COHORT. THE BIOMARKER DISCOVERY INITIATIVES ARE FINE BUT NOT VERY SUCCESSFUL AND THE VALIDATION GOAL OF A LOT OF CONSORTIA CAN HE HAVE ARE NOT BEING MET BECAUSE THERE ARE NO REALLY GOOD-BYE MARKERS FOR EARLY DETECTION OF PANCREATIC DETECTION SO I WOULD LIKE US TO CONSIDER REFINING WHAT WE'RE ASKING THE INVESTIGATORS TO DO. EVERYONE IS GOING BACK TO THE ROUND -- SQUARE ONE TO TRY TO DISCOVER NEW BIOMARKERS AND IT'S ALL OVER THE MAP WHAT THEY ARE DOING, IT WOULD BE GREAT IF DIRECTED BY BIOLOGY OF THE TUMOR WHICH CALLS FOR US TO BETTER UNDERSTAND THE BIOLOGY OF PANCREATIC CANCER. SO THERE'S A LOT OF STILL UNKNOWNS FOR US. >> I WANT TO START BY ECHOING THANKS TO JIM AND TONY FOR LEADING THIS AND SHEILA AND DEBBIE WHO DID A SUPER JOB BRINGING US BACK TOGETHER. JIM, I WANT TO THANK YOU FOR MENTIONING NEUROIMAGING SO MUCH IN THE PRESENTATION. I WAS PART OF THE 2014 AND DIDN'T HAVE A LOT TO OFFER AT THAT POINT. WHAT I IDENTIFY FOLLOW-UP ON THEMES THAT GLORIA RAISED IS BASIC INVESTMENTS IN IMAGING TECHNOLOGY WHICH ARE NOT PANCREATIC FOCUS FROM CANCER IMAGING PROGRAM AND OTHER AREAS HAVE -- I THINK THE OPPORTUNITY FOR IMAGING AND DIAGNOSTIC STANDPOINT IN GENERAL IS TO LEVERAGE THIS TECHNOLOGY BY INTEGRATING IT IN OTHER FACETS OF THIS EFFORT. I WANT TO HIGHLIGHT TWO. JIM MENTIONED DEVELOPMENT OF TECHNIQUES THAT CAN HELP US UNDERSTAND THE INTERACTION BETWEEN BIOLOGY AND TREATMENT EFFICACY. ALSO ANIMAL MODELS. VERY RECENTLY, CANCER IMAGING PROBLEM IS A U 24 MECHANISM ON CLINICAL TRIALS DESIGNED TO BRING IMAGING TECHNIUES UNIQUE TO ANIMAL MODELS IN A STANDARDIZED WAY. IN A STATISTICAL FASHION MY COLLEAGUE JUST JOINED THAT CLUB BUT FOCUSED ON PROFUSION PHON PANCREATIC CANCER, IT'S ONE OF THE FEW WHERE BLOOD FLOW IS LOWER IN THE TUMOR THAN SURROUNDING TISSUE, SO THE BARRIER TO SYSTEMIC DRUG DELIVERY IS POORLY UNDERSTOOD AND THIS WILL BE LEVERAGES TECHNOLOGY ADVANCEMENTS FROM THAT STANDPOINT. THE OTHER THING I FOUND FOR THIS IS EVOLVING ROLE THAT ENDOSCOPIC ULTRASOUND HAD AND PRIMARY DIAGNOSTIC OPPORTUNITIES. IN A COUPLE OF INVESTMENTS IN ULTRASOUND CONTRAST AS WELL AS POSSIBLY OPTO IMAGING TECHNOLOGY IS BRINGING MOLECULAR CAPABILITIES TO THAT. HERE IS A TREMENDOUS OPPORTUNITY FOR INTEGRATION. IF WE IDENTIFY BIOMARKERS THAT ARE NOT PERFECT BIOMARKERS BUT GUIDE US DOWN THE RIGHT PATHWAYS TO KNOWING WHAT WE ARE LOOKING FOR WITH IMAGING TECHNOLOGIES, THAT KIND OF INTEGRATION I THINK COULD REALLY CHANGE THE LANDSCAPE OF BOTH EARLY DETECTION AND DIAGNOSIS. SO I WAS VERY EXCITED TO BE PART OF THIS, AND WAS REALLY EXCITED TO SEE THAT THESE BASIC INVESTMENTS IN TECHNOLOGY WHICH MAY NOT HAVE BEEN ORIGINALLY DIRECTED TOWARDS PANCREATIC CANCER WERE NOW POISED TO CONTRIBUTE ON DIAGNOSTIC AND THERAPEUTIC SIDE. >> CAN I MAKE ONE MORE COMMENT. BECAUSE LYNN IS -- IT WOULD BE SELF-SERVING FOR LYNN TO SAY THIS BUT THIS IS -- INITIATIVE NCI IS INVOLVED WITH PANCREATIC CANCER WITH PUBLIC PRIVATE PHILANTHROPY PARTNERSHIP HAS BEEN AMAZING TO BEHOLD. WHAT HAS HAPPENED IS THESE LARGE PHILANTHROPIC ORGANIZATIONS AND NCI ARE WORKING TOGETHER AS A TEAM TO WORK ON COMMON PROBLEMS TO SOLVE. IT'S BEEN WONDERFUL TO SEE THE PARTNERSHIP AND CO-FUNDING OF INITIATIVES SO I APPLAUD THE NCI FOR BEING OPEN TO IT. >> WE HAVE GOT -- I KNOW -- GIVE ANOTHER FIVE MINUTES TO THIS AND WE CAN CARVE IT INTO OUR BREAK. OTHER COMMENTS, JIM, DO YOU HAVE ANY COMMENTS? >> THIS MIGHT BE A QUESTION FOR NED AS WELL AS JIM. IN THIS CONGRESSIONAL INITIATIVE WHAT IS THE NCI PLAN. IS THERE A PLAN FOR SEEKING RENEWAL OF THIS ACT? LOOKING AT OTHER DISEASES FOCUSING ON PANCREATIC AND SMALL CELL AND HOW MUCH DETAIL YOU'RE LOOKING FOR THIS WORKING GROUP TO GIVE US A FIVE YEAR VISION. >> THE LAW IS -- HAS (INDISCERNIBLE) VARIOUS RUERING FRAMEWORK WE TALKED ABOUT. WHETHER IT'S NEW OR SEE A DIFFERENT DISEASE FOCUS OR WHAT NOT IS UP TO THE CONGRESS, NCI IS REAL OPINION ON THIS TOPIC. I HAVE TO SAY, WHEN I WALK AROUND CONGRESS AND TALK, I DON'T GET A LOT OF QUESTIONS ABOUT WHETHER THE RECALCITRANT ACT SHOULD GO. THE PLAN IS TO MEET REPORTING REQUIREMENTS OF SMALL CELL AND PANCREATIC CARCINOMA AND THEN CONGRESS HAS TO DO NEXT IN THIS REGARD. THERE IS -- IT'S AN INTERESTING DANCE BETWEEN THE CONGRESSIONAL DESIRE TO SUPPORT THE NCI AND ALSO TO TELL US WORKING SPECIFIC TOPICS SENSE OF LACK OF PROGRESS. SO WE TRY AND AS I ALLUDE TO IN MY PRESENTATION BALANCE THAT TO GREAT DEAL AND IT'S BETTER FOR US IF WE IDENTIFY THOSE DIFFICULT CANCERS FOR THE CONGRESS ASKS TO WORK ON THEM. LIVER CANCER BEING AN EXAMPLE. THERE'S DISCUSSION OF A NEW LEGISLATION LIVER CANCER AND THAT'S AN AREA WE SHOULD BE WORKING ON WHETHER OR NOT CONGRESS ASKED US. >> THAT FOCUSED YOU ABODING GIVE YOU MONEY, IS THAT RIGHT? >> THAT'S CORRECT. >> ACCURATE. >> JUST TO FOLLOW-UP ON THAT POINT. AS PATIENT ADVOCATE REPORTED COALITION CALLED DEADLY CANCER COALITION WHICH IS A COALITION OF PATIENT ADVOCACY GROUPS THAT REPRESENT RECALCITRANT CANCER, WELCOME CONVERSATION ABOUT WHERE TO GO NEXT WITH RECALCITRANT CANCER RESEARCH ACT. THE ACT ITSELF IS A PRODUCT OF PATIENT ADVOCACY LARGE MEASURE LED BY PAN CAM BUT WHERE THIS GOES, WE ARE OPEN TO CONVERSATION TO HELP THE NCI THINK THROUGH WHAT IT WOULD LIKE TO DO NEXT ON THIS TOPIC ANY TIME. COALITION MEETS QUARTERLY. >> I THINK IT GIVES ADDITIONAL SINING OPPORTUNITY BUT -- SCIENTIFIC OPPORTUNITY BUT WE DIP HEAR ABOUT STEM CELLS DISEASE, IS THERE GROUPS WORKING ON THAT, WHICH IS ACTUALLY STRATEGY BUT DIDN'T INCLUDE A DISEASE SO DIFFICULT. >> I MEAN, IT CAME UP A LITTLE BUT IT HAS NOT BEEN A MAJOR FOCUS IN THIS PARTICULAR DISEASE. AT THIS POINT IN TIME. THERE ARE SOME PEOPLE WORKING ON IT BUT IT DIDN'T RISE TOP ONE OF THE TOPICS BROUGHT UP BY THE COMMITTEE BEING HIGH PRIORITY. >> JIM IS ON THE PHONE. I WAS PLEASANTLY SURPRISED BY THE POSITIVE, STRONGLY POSITIVE RANDOMIZED TRIAL ADJUVANT PANCREATIC CANCER PRESENCED AT ASCO FOR -- VERSUS JIM SIDE BEAN. I WONDER I DIDN'T SEE THAT COMING. WONDER HOW THE RESULTS OF THAT TRIAL INFLUENCE IN CYTOTOXIC AGENT TRIALS PANCREATIC CANCER, OUTSIDE OF THE ADJUVANT SETTING FOR EXAMPLE. WHAT IF ANYTHING SHOULD NCI DO DIFFERENTLY BASED ON THESE RESULTS? >> GOOD QUESTION. I THINK FULLFERNOX IS RECOGNIZED DESPITE LIMITATION IN TERMS OF TOXICITY AND THE LIKE AS PROBABLE THE SINGLE BEST REGIMEN FOR MANAGEMENT OF PANCREATIC CANCER, THE TRIALS THAT EVOLVED STARTING WITH THE METASTATIC SETTING AND UTILIZE IN THE NEOADJUVANT SETTING TO DOWN STAGE CANCER, PARTICULARLY THOSE TUMORS BORDERLINE RESECTABLE. THEY HAVE SOME VASCULAR INVOLVED BUT WITH IMPROVED SURGICAL TECHNIQUE CAN PERHAPS IN COMBINATION WITH RADIATION THERAPY CAN BE RESECTED. THE RESULT IN ADJUVANT SETTING WAS ACTUALLY QUITE IMPRESSIVE. I DON'T KNOW. THIS MAYBE CONTROVERSIAL BUT I'M NOT SURE OTHER THAN THE WORK NOW BEING DONE TO REFINE THE UNDERSTANDING OF PATIENT POPULATIONS LIKELY TO RESPOND TO DNA DAMAGING AGENTS SUCH AS CISPLATIN JUST BASED ON BETTER UNDERSTANDING OF THAT SUBSET OF FOLKS THAT HAVE HRD DEFECTS, DUE TO EITHER SPECIFIC GENETIC ALTERATION -- SOMATIC MUTATIONS AND OCCASIONAL GERM LINE AS WELL. SO WE CAN REFINE THE PATIENT POPULATION THAT WE USE REGIMEN LIKE THAT BUT I THINK THE INVESTMENT FROM NCI REALLY SHOULD GO IN THE OTHER AREAS THAT THE WORKING GROUP IDENTIFIED. I THINK PARTICULARLY UNDERSTANDING THE BIOLOGY AND SIGNALING THAT IS OCCURRING WITHIN THE MICROENVIRONMENT AND THE METABOLIC ALTERATIONS CONFERRED BY KRAS GROWING IN A VERY HOSTILE MICROENVIRONMENT IDENTIFYING TARGETS PUSHING BEYOND CYTOTOXIC. THAT'S MY BIAS, THE WORK BEING DONE, IT IT'S GREAT WHEN IT WORKS WELL FOR PATIENTS IT'S AN IMPRESSIVE AND GRATIFYING TO HAVE THAT HAPPEN. BUT IF WE'RE GOING TO MAKE SIGNIFICANT IMPACTS ON THIS DISEASE, WE NEED TO BE INVESTING IN THE SCIENCE, THAT IS GOING TO HELP US IDENTIFY BETTER TARGETS AND MORE PRECISE MANAGEMENT OF PATIENTS. THAT'S MY PERSPECTIVE, IT MAY NOT JIVE WITH EVERYBODY. >> CAN YOU PRESENT T IT IN A QUICK WAY WITH A QUESTION ANSWERED QUICKLY? >> I WOULD JUST I'M HOWARD FINGERT, INDUSTRY REPRESENTATIVE. I'M REALLY INTERESTED IN UNDERSTANDING PLANS GOING FORWARD TO IMMUNOONCOLOGY EFFORTS THAT MULTIPLE INDUSTRY SPONSORS ARE DOING BY DIALOGUE WHERE NCI IS OR PRECISION PROMISE PROTOCOL. WHICH SOME ARE PARTICIPATING IN AND SOME NOT. THERE ARE INDUSTRY TRIALS GOING ON BY BIG SPONSORS NOW AND SMALL SPONSORS IN THE PANCREATIC CANCER FIELD WITH THAT DIVERSITY, I DON'T KNOW IF THEY ARE COLLECTING THE RIGHT BIOMARKERS OR CONDUCTING THE RIGHT TRIAL. THIS IS -- THERE IS -- YOU ARE RIGHT. THERE'S ONGOING ACTIVITY IN THIS SPACE, FROM MY PERSPECTIVE BEING SOMEONE THAT PARTICIPATES IN SUBSET AT LEAST OF THESE TRIALS, IT IS NOT COORDINATED IN ANY WAY. AND I -- AS POINTED OUT IN THE REPORT, I DON'T THINK THAT ALL THE TRIALS ARE OPTIMALLY DESIGNED TO REALLY GAIN INFORMATION WHY OR WHY NOT A PARTICULAR INTERVENTION WORKED IN PATIENTS WITH PANCREATIC CANCER, NOT AN EASY THING TO DO BUT IF WE DON'T WORK ON THE PROBLEM WE'RE NEVER GOING TO GET THERE. IT WOULD BE WONDERFUL TO HAVE A LITTLE MORE COORDINATED EFFORT, DIFFICULT THING TO DO. BUT RIGHT NOW EACH -- IN MANY CASES EACH COMPANY IS GOING THEIR OWN DIRECTION, THEY HAVE THEIR OWN AGENT, SECOND GENERATION CHECK POINT INHIBITOR S IS A COMMON TRIAL BEING PROMOTED OR COMBINATION OF FIRST GENERATION CHECK POINT INHIBITORS WITH CHEMOTHERAPY. BUT THERE ISN'T A GREAT COORDINATION, THAT I SEE, AT LEAST FROM WHERE I SIT. >> VERY GOOD SESSION, JIM, THANK YOU SO MUCH, I APOLOGIZE FOR THE NETWORKING ISSUES HERE. WE'RE GOING TO BREAK NOW, THERE WILL BE REPORT, CIRCULATED SO IF OTHERS HAVE QUESTIONS PLEASE ADD IT THERE. LET'S BREAK NOW. WE'LL MEET AT 10:52. TEN MINUTE BREAK. OKAY? FOR ALL OF YOU GUYS, THANK YOU. 9:50. WRONG TIME ZONE. BARRY HAS BEEN A FIXTURE AT THE NCI AND HAVE KNOWN HIM FOR A HUNDRED YEARS. WHEN HE WAS DOWN IN FLORIDA, BUT IT'S GREAT PLEASURE TO HAVE HIM GIVE HIS VISION FOR CANCER PREVENTION AND IMPLEMENTATION. AND THIS WILL FRAME THE NEXT HOUR SO OF PREVENTION. TO HELP ADVISE THE NCI AND DCP IN TERMS HOW WE MIGHT HELP YOU. SO INTRODUCE A SERIES OF PREVENTION TOPICS AND OVERVIEW AND FOLLOW THIS UP WITH COUPLE OF OTHER PRESENTATIONS BY DR.S THOMPSON AND UNGER BUT I WANT YOU THE TAKE THE LEAD HERE BARRY. >> THANKS, PAT. >> NOTHING HAPPENED. OKAY. THANK YOU. SO FIRST I HOPE YOU WILL PERMIT ME TO DIE DEGREES FOR JUST A MOMENT. AS YOU KNOW FROM NED SHARPLESS UPDATE IN THE CURRENT ISSUE THE CANCER LETTER I WILL BE RETIRING ON JANUARY 3RD. SO MY INTRODUCTORY REMARKS TODAY ON THE VISION FOR CANCER PREVENTION RESEARCH AND IMPLEMENTATION ARE A BIT OF RETROSPECTIVE ON MY SEVEN YEARS AS DIVISION DIRECTOR. A MAJOR GRATIFICATION OF BEING DIVISION DIRECTOR IS PRIVILEGE OF IMPLEMENTING THAT VISION WITH TRULY WOUND OF PEOPLE WITH MY DIVISION OR OTHER COLLEAGUES AROUND THE COUNTRY AND EVEN AROUND THE WORLD OVER THOSE YEARS. ALSO FOR THAT REASON I'M FOREVER GRATEFUL TO HAROLD VARMUS WHO PULLED ME OUT OF MY PREVIOUS RETIREMENT SEVEN YEARS AGO TO OFFER ME WHAT I CONSIDER TO BE ABSOLUTE BEST JOB IN MY FIELD. ALWAYS THANK HIM FOR THAT. TALKS BY IAN THOMPSON, GERALD UNGER, SZABO AND DR. HAWK AND MS. CAUSE SKILL SCIENCE PROVIDE A FEW EXAMPLES OF WHAT I FEEL PRIVILEGEDDED TO HAVE SERVED AND WHY I ANTICIPATE CONTINUED PROGRESS. BUT ALSO AS PAT SAID WE LOOK TO YOU FOR ADVICE AND HELP US FRAME OUR THINKING AND FRAME FUTURE OF DIVISION FUTURE ACTIVITIES IMPLEMENTATION OF VISION. NOW MY INTRODUCTORY REMARKS. THIS IS A FRAMEWORK WE THINK ABOUT AS WE PLAN CANCER PREVENTION ACTIVITIES AND SCREENING ACTIVITIES. THE LINEAR ASPECT OF THAT TRIAL CAME FROM PETER GREENWALD WHO WAS A PIONEER DEVELOPING CANCER PREVENTION AND HE DEVELOPED THE FIVE PHASES THAT RANGE FROM HYPOTHESIS DEVELOPMENT ALL WAY TO IMPLEMENTATION OF PROJECTS. AND I -- THIS WAS A USEFUL FRAMEWORK BUT WE ADDED TO THAT BECAUSE WE FELT IT LOOKED A LITTLE TOO LINEAR. WE WANTED TO CONVEY THE CONCEPT THAT LARGE SCALE POPULATION BASED STUDIES AN IMPLEMENTATION PROJECTS NOT ONLY TEST HYPOTHESES BUT THEY PROVIDE NEW HYPOTHESES SO THAT TAKES US ALL THE WAY BACK TO THE BEGINNING TO TEST OUR HYPOTHESES. LET ME GIVE YOU AN EXAMPLE ONE WHICH YOU HAVE HEARD ABOUT, THE OTHER YOU'RE GOING TO HEAR ABOUT, IS FREE TRIAL THAT YOU HEARD ABOUT, WE HAVE SURPRISING RESULT. THAT IS ONE OF THOSE ASPIRIN APPEAR TO HAVE NO NET BENEFIT AND MAY HAVE HAD ACTUAL HARM IN THE ELDERLY. THAT WAS UNANTICIPATED BUT IT PROVIDES THE OPPORTUNITY TO ASK WHY BASIC BIOLOGICAL QUESTIONS THAT NEED TO BE PURSUED IF THOSE RESULTS HONED OUT. AS YOU WILL HEAR LATER THE PROSTATE CANCER PREVENTION TRIAL BIOLOGICAL UNDERSTANDING OF THE PROGRESSION OF PROSTATE CANCER BUT WE LEARNED A LOT FROM IT AND IAN WILL GET INTO THAT IN A BIT BUT IT TAUGHT US YOU CAN'T MAKE ASSUMPTIONS ABOUT END POINTS, IN THIS CASE I THINK IT'S FAIR TO SAY THE GLEASON SCORE THAT LED TO ALL THE SKEPTICISM ABOUT THE USE OF -- FOR PREVENTION MAY HAVE BEEN MISLEADING AND YOU WILL GET AN UPDATE TO THAT. THE OTHER THING THAT IS VERY IMPORTANT TO MY DIVISION IS RESEARCH TRAINING, TRAINING THE NEXT GENERATION OF SCIENTISTS AND I WILL TELL YOU ABOUT THAT. FINALLY, THE AREA OF CANCER PREVENTION IS ONE OF THE TOP INTERESTS OF THE PUBLIC AND OTHER REPRESENTATIVES. SO A CRITICAL ROLE OF THE DIVISION IN THE INSTITUTE IS PUBLIC AND PROFESSIONAL EDUCATION. TO THAT END I HAVE BEEN VERY PROUD TO SERVE OVER THE YEARS IN THE SCREENING AND PREVENTION EDITORIAL BOARD, THE PDQ, PHYSICIAN DATA QUERY. SO ON TO THE VISION WE TRIED TO FOLLOW. OUR KEY VISION IS REDUCTION IN INCIDENCE AND ULTIMATE ELIMINATION OF INVASIVE CANCERS, THAT ARE POTENTIALLY LIFE THREATENING. THAT LESS PHRASE IS PARTICULARLY IMPORTANT BECAUSE AS WE DEVELOP MORE AND MORE SENSITIVE TOOLS TO DETECT TUMORS IN EARLY LESIONS WE HAVE DISCOVERED THAT SOME OR EVEN MANY LESIONS THAT WE DETECT ARE NON-LIFE THREATENING. THIS OFFERS US NEW AVENUES FOR UNDERSTANDING THE BIOLOGY AND TRYING TO SORT OUT THE DETECTED LEAGUES THAT ARE LIFE THREATENING FROM THOSE NOT LIFE THREATENING AND SHOULDN'T BE TREATED. WE CAN DIMINISH THE HARM OF MANY OWN DETECTION TOOLS IF WE LEARN WHICH LESIONS SHOULD BE TREATED AND WHICH SHOULDN'T. THIS IS HOW I WILL COVER THE AREAS I USE TO IMPLEMENT THAT VISION, PREVENTIVE AGENT DEVELOPMENT BIOMARKER RESEARCH AND THE COMMUNITY BASED STUDIES TO TEST HYPOTHESES AND DEVELOP NEW ONES. N COMMUNITY ONCOLOGY RESEARCH PROGRAM IS A LABORATORY FOR THAT EFFORT. AND FINALLY, TRAINING THE NEXT GENERATION WITH RESPECT TO PREVENTIVE AGENT DEVELOPMENT, WE ENGAGED IN IMMUNOPREVENTION INCLUDING DEVELOPMENT OF FRAME SHIFT VACCINE IN OUR PREVENT PROGRAM. FOR LINT SYNDROME AND MUTATIONS THAT LEAD TO FRAME SHIPS AND IMMUNOBRIDGING TRIAL WITH THE HPV VACCINE. AS SOME OF YOU HAVE HEARD THERE'S ONGOING TRIAL COMPARING ONE DOSE HPV VACCINE TWO DOSES HPV VACCINE THAT WOULD BE A MAJOR GAME CHANGER AROUND THE WORLD. MANY COUNTRIES CAN'T EASILY AFFORD OR IMPLEMENT HPV VACCINATION FOR THE ENTIRE POPULATION. SO YOU CAN IMAGINE WHAT HAPPENS IF YOU CUT DOWN -- COULD CUT DOWN THE DOSE TO TWO OR EVEN ONE AROUND THE WORLD. ALSO WE ARE LOOKING AT AGENTS THAT HAVE BEEN OUT THERE A LONG TIME, FOR EXAMPLE ASPIRIN. NED COVERED A SPRING TRIAL WHICH AS I MENTIONED GAVE US SOME SURPRISES. IT TAUGHT TWO THINGS. ONE IS THAT YOU CAN'T ASSUME YOUR INTUITION IS GOING TO WORK. BACK BEFORE I TOOK THIS JOB, I SOUGHT ADVICE FROM THOUGHT LEADERS IN THE COUNTRY, ONE WAS BERNARD LE VINE. HE TOLD ME IS THE ONLY THING YOU HAVE TO KNOW IS ASPIRIN IS ALWAYS THE ANSWER TO CANCER. THAT WAS A COMMON ASSUMPTION. UP UNTIL THE SPRING TRIAL PEOPLE CARRIED IT IN THEIR HEAD AND THOUGHT NO DOWN SIDE TO TAKING ASPIRIN BECAUSE OF ADDED BENEFIT OF REDUCTION IN CANCER AND NOW WE HAVE LEARNED IT'S A LITTLE MORE NUANCED AND COMPLICATED THAN THAT. WE TRIED TO REPURPOSE EXISTING DRUGS. AN WE KNOW OUR TRIALS ARE LARGE EXTREMELY EXPENSIVE AND THEREFORE VERY DIFFICULT TO GET THROUGH COUNCIL. SO WE LOOK -- ANOTHER THING WE LEARNED IS THAT SOMETIMES WE CAN GET THE WRONG INDICATION FROM EPIDEMIOLOGY EVEN IF IT IS LINKED TO VERY TIGHT MOLECULAR STORY, WE THOUGHT EVERYTHING WAS ALIGNED WITH ANTIOXIDANTS AND BETA CAROTENE AND IT TOOK A LARGE TRIAL. TO FIND OUT THAT OUR ASSUMPTIONS AND INTUITIONS DON'T ALWAYS PAY OFF. BUT THAT REASON WE DON'T WANT TO RUSH INTO LARGE PREVENTION TRIALS WITHOUT ALL THE INFORMATION WE CAN GET. ONE TO DO LESS EXPENSIVELY, LOOK TO TRIALS THAT HAVE BEEN DONE USING DRUGS THAT ATTACKS ONCOLOGY RELATED CANCER RELATED PATHWAYS. WHY WE LOOK TO METAPHOR MAN IN THE DIABETES TRIAL THAT WAS A RANDOMIZED TRIAL COMPARING METAPHORMAN TO PLACEBO TO LIFESTYLE CHANGE. AND PREVENT DIABETES. THAT IS ONGOING EFFORT. IF YOU HEAR FROM THE CANCER PREVENTION STUDY, WON'T GO INTO DETAIL IAN TAUGHT US AN AWFUL LOT ABOUT DOING TRIALS AND IMPORTANCE OF NOT ONLY DOING THEM BUT FOLLOWING THE PARTICIPANTS LONG TERM. FINALLY AS YOU ALL KNOW UNLIKE THERAPEUTIC ONCOLOGY WHICH WE ARE WILLING TO TOLERATE SUBSTANTIAL TOXICITY IN EXCHANGE FOR BENEFITS OR POTENTIAL BENEFITS, IN PEOPLE WHO ARE SUFFERING FROM CANCER, IN PREVENTION AREA WE CAN BARELY TOLERATE ANY TOXICITY SO EVEN AN EFFECTIVE DRUG CAN BE ABANDONED COMPLETELY IF IT HAS MODEST TOXICITIES. SO FOR THAT REASON WE LOOK FOR NOVEL DELIVERY METHODS TO REDUCE TOXICITIES. AND WE'RE STUDYING THAT IN OUR EARLY CLINICAL TRIALS, U WILL HEAR FROM DR. SZABO FROM 0 TO PHASE 2 DON SOURCE YUM BUT WE'RE STUDYING TAMOXIFEN AND -- FOR BREAST CANCER AND AEROSOLIZED DRUGS TO PREVENT LUNG CANCER HOPEFULLY TO DELIVER EFFECTIVE AGENT DIRECTLY TO TARGET. WE HAVE THREE CRITICAL COMPONENTS OF PREVENTIVE AGENT DEVELOPMENT PROGRAM. THREE LEGS TO THE THREE LEGGED STOOL. WE HAVE PRE-CLINICAL DEVELOPMENT THE PREVENT PROGRAM, EARLY PHASE TRIALS AND NCI IMMUNITY ONCOLOGY RESEARCH PROGRAM TO TEST HYPOTHESES IN THE COMMUNITY, YOU WILL HEAR MORE DETAIL ABOUT LAST TWO LEGS, PREVENT PROGRAM NOT GOING TO COVER MUCH BUT THE FLOW OF DEVELOPMENT IS DEPICTED IN THIS CHART. FROM MOLECULAR TARGETS AND PRE-CLINICAL EFFICACY IN OUR PREVENT PROGRAM. ANYTHING THAT SUCCEEDS THERE WE THINK ABOUT PUTTING INTO OUR PHASE 0 THROUGH 2 TRIALS FOR THE FIRST IN HUMAN TESTING AND THEN FINALLY FOR LARGER PHASE 3 TRIALS, ALONG THE WAY AS YOU HEARD NED SHARPLESS EMPHASIZE THIS MORNING, EARLY DETECTION RESEARCH NETWORK HELPS REFINE AND VALIDATE BIOMARKERS THAT CAN HELP IN TRANSITION FROM PHASE TO PHASE. EARLY DETECTION BIOMARKER RESEARCH, THE BIG PART OF THE PROGRAM IS NOT EARLY DETECTION BUT MITIGATION OF OVERDIAGNOSIS, IT IS PURE HARM. IF YOU DETECT AND OVERDIAGNOSED LESION. I CAN'T THINK OF ANYTHING BENEFICIAL ABOUT IT. YOU LABEL A PERSON MAKE THEM A CANCER PATIENT UNNECESSARILY AND IMMEDIATELY OFTEN START LIFE CHANGING AND OFFICE VERY TOXIC THERAPY. SO IT'S IMPORTANT TO KNOW AS WE DEVELOP MORE AND MORE SENSITIVE TOOLS, WHO NEEDS THAT THERAPY. TO THAT END YOU HEARD ABOUT THE MOLECULAR CELLULAR CHARACTERIZATIONS OF SCREEN DETECTED VISION OR MCL CONSORTIA, THIS IS THE INTERFACE BETWEEN BIOLOGICAL UNDERSTANDING AND APPLICATION TRANSLATION TO ACTUAL UTILITY AND THAT'S WHY DINA SINGER AND I WORKED ON DEVELOPING THIS PROGRAM BETWEEN THE TWO DIVISIONS WHERE YOU HAVE CANCER BIOLOGISTS WORKING HAND IN HAND WITH TRANSLATIONAL SCIENTISTS. PRE-CANCER ATLAS OR PCA IS PART OF THE HUMAN TUMOR ATLAS NETWORK. THERE ARE A LOT OF ADDITIONAL COMPLEXITIES AS I HINTED. IN THE DETECTION. AND ANALYSIS AND PREDICTION PROGNOSIS IN PRE-CLINICAL LESIONS AND THAT'S WHY HALF OF THE HUMAN TUMOR ATLAS NETWORK IS DEVELOPED, IS GOING TO BE IN SECTORS DEVOTED TO PRE-CLINICAL LESIONS. THE TEAMIST TRIAL THE RANDOMIZE TRIAL OF 2D DIGITAL MAMMOGRAPHY WITH VERSUS WITHOUT TUMOR SYNTHESIS, ATTEMPT TO TAKE A NEW TECHNOLOGY BEFORE THE TRAIN LEAVES IT IS STATION AND BEFORE EVERYONE ASSUMES THAT EARLY DETECTION IS NECESSARILY ALWAYS A BENEFIT. WHENEVER YOU APPLY TWO TESTS, YOU ARE GOING TO FIND MORE CANCER THAN YOU APPLY ONE TEST THAT'S INESCAPABLE CIRCUMSTANCE. BUT YOU CAN'T BE CONFIDENT OF A RANDOMIZED TRIAL WHETHER EARLY DETECTION OF MORE LESIONS IS ALL GOOD, ALL BAD OVERDIAGNOSIS OR MORE LIKELY SOMEWHERE IN BETWEEN. SO IT REQUIRES A RANDOMIZED TRIAL WITH BIOLOGICAL BACKUP. AND WE LOOK AT POST THERAPY SURVEILLANCE TO SEE IF WE CAN GET HINTS OF HOW FOLLOW-UP OF PREVIOUSLY TREATED HOPE ANY CURED PATIENTS MAY GIVE US FOR NOT ONLY MANAGEMENT BUT EARLY DETECTION DOWN THE ROAD AND SCREENING. YOU HEARD ABOUT THE NEW ONSET DIABETES COHORT, WE HAVE TWO OF THE LEADERS, THAT COHORT HERE IN THE ROOM, AND -- GLOVER RA PETERSEN. WE ARE VERY PLEASED TO USE THAT AS A HIGH RISK POPULATION TO IDENTIFY PEOPLE AT INCREASE RISK FOR PANCREATIC CANCER TO GIVE NOT ONLY HINTS ABOUT EARLY DETECTION BUT WHICH POPULATIONS MAY BENEFIT FROM PREVENTIVE INTERVENTIONS. YOU HEARD ABOUT PANCREATIC DETECTION CONSORTIA AND YOU HEARD ABOUT CONSORTIA TRANSLATIONAL RESEARCH AND EARLY DETECTION OF LIVER CANCER THAT YOUR SUBCOMMITTEE HAS ALREADY REVIEWED. MOVING TO THE N CORE NCI COMMUNITY ONCOLOGY RESEARCH PROGRAM, THIS IS A MAP OF OUR COVERAGE OF THE COUNTRY OF COMMUNITY SITES IN MINORITY BASED COMMUNITY SITES. THIS IS NOT ONLY A MECHANISM OF ACCRUAL SUBSTANTIAL PROPORTION OF PATIENTS, CANCER PATIENTS TO THE NCTN TRIALS, IT ADDED FOR EXAMPLE LARGE PROPORTION OF THE MATCH PATIENTS WHO ENTERED THE TRIAL, BUT IT'S DEVOTED PREVENTION AND TO SCREENING. AND IT HELPS US AS A LABORATORY FIGURE OUT WHETHER THINGS THAT WORK IN THE MAJOR CANCER CENTERS ARE APPLICABLE IN TO COMMUNITIES AND SITES. LAST TRAINING NEXT GENERATION OF PREVENTION AND SCIENTISTS HAS BEEN A REAL SOURCE OF PRIDE TO DIVISION. THIS IS A CANCER FELLOWSHIP PROGRAM WHICH IS A MULTI-DISCIPLINARY POST-DOCTORAL PROGRAM, TRAINING THE FUTURE LEADERS. AND WE OFFER THEM RESEARCH THAT SPANS FULL SPECTRUM OF THE SLIDE THAT I SHOWED YOU FROM BASIC BENCH RESEARCH AND HYPOTHESIS DEVELOPMENT IN THE LABORATORY ALL THE WAY TO POPULATION BASED STUDIES, IT CELEBRATED 30th ANNIVERSARY LAST YEAR AND IT'S BEEN ALONG THOSE DECADES THROUGHOUT THOSE DECADES PROVIDING MULTI-DISCIPLINARY TRAINING FOR POST-DOCTORAL FELLOWS THAT SPAN THAT SPECTRUM, THERE'S 37 FELLOWS THAT WORK ACROSS THE DIVISIONS. WE DON'T CARE WHICH DIVISION THEY WORK IN, AS A MATTER OF FACT A MINORITY OF THEM WIND UP CHOOSING TO WORK IN THE DIVISION OF CANCER PREVENTION. WE DO CARE THAT THEY'RE PROPERLY TRAINED IN THINKING ABOUT PREVENTION AND SCREENING AND THEY CAN THAT TRAINING AND THAT NEW DEPTH INTO WHATEVER FIELD OF RESEARCH THEY ARE DOING AND WE COLLABORATE WITH THE FDA WHERE WE HOPE THEY WILL BE INSTRUMENTAL IN DEVELOPING PREVENTIVE AGENTS. FINALLY WE HAVE TWO SUMMER COUNSELORS ONE ON BASIC PRINCIPLES OF CANCER PREVENTION AND CONTROL AND ONE ON MOLECULAR PREVENTION. SO WITH THAT, I WHETHER STOP AND THINK WE'LL RESERVE QUESTIONS AND HEAR COMMENTS AT THE END OF ALL THE TALKS. >> THANK YOU SO MUCH. NEXT UP IS IAN THOMPSON, PRESIDENT OF SANTA ROSA HOSPITAL CENTER AT UT SAN ANTONIO. IAN WAS INSTRUMENTAL IN DEVELOPING THE -- PREVENTION TRIAL. WHAT WE ASKED HIM TO DO IS BASICALLY GIVE A PRESENTATION OF THIS, BASICALLY WHERE WE HAVE BEEN IN THE PAST WITH SOME OF THE PREVENTION TRIALS. WE WILL HAVE A COUPLE OF OTHER PRESENTATIONS THAT WILL TAKE US INTO THE PRESENT AND FUTURE. WE WILL HAVE -- AFTER IAN AND DR. UNGER PRESENT WE WILL HAVE AT THE END OF THE TABLE TIME FOR QUESTIONS, IAN. >> THANK YOU VERY MUCH, PAT. NICE TO BE HERE, NICE TO BE AMONG FRIENDS AND COLLEAGUES AND I MAY POINT OUT SEVERAL OF YOU DURING THE COURSE OF THIS PRESENTATION. JOE AND I WILL TAG TEAM THIS. I WILL GIVE HISTORY, TAKE YOU PARTWAY THROUGH, JOE WILL THEN TALK ABOUT INTEGRATION OF BIG DATA AND PROGRAMS THAT ALLOW US TO CONTINUE TO ACCOMPLISH WHAT WE HAVE DONE LONG TERM. AND THENLY TAKE YOU THROUGH THE END AND PERHAPS THE LONG TERM IMPLICATIONS OF THIS. THE CHALLENGE OF PROSTATE CANCER IS THAT GENTLEMEN IN THE ROOM THREE QUARTERS OF US WILL HAVE IT DURING OUR LIFETIME. THREE TO FIVE PERCENT OF US WILL -- AS MANY AS 16% WILL BE DETECTED. WE CAN DETECT TUMORS BUT AS BARRY HAS BEEN ONE OF THE GREAT PROTAGONISTS IN ALL THIS AND HELPING US TO UNDERSTAND THIS, THERE'S A SIGNIFICANT RISK OF OVERDETECTION AND TREATMENT CARRIES WITH IT QUITE A FEW TOXICITIES. TO INCLUDE ERECTILE DYSFUNCTION INCONTINENCE, GI TOXICITY AND POTENTIAL RISK OF SECONDARY MALIGNANCY. WE CANNOT IGNORE THE FACT 3 TO 6% OF US MEN WILL DIE FROM THIS DISEASE. FOR DIAGNOSED WITH SYMPTOMS WHEN WE'RE SYMPTOMATIC MOST PEOPLE WILL HAVE METASTATIC DISEASE AND MOST MEN WITH METASTATIC DISEASE DESPITE THE NUMEROUS NEW THERAPIES THAT WE HAVE AVAILABLE, MOST OF THOSE MEN WILL DIE FROM THEIR DISEASE AND THE TREATMENTS THEMSELVES BECAUSE THOSE WHO MANAGE THESE PATIENTS WITNESS THIS THEY ARE EXTREMELY MORBID AND FROM A HEALTH SYSTEM STANDPOINT IT CAN BE EXTREMELY EXPENSIVE. WE KNOW SCREENING WITH PSA DETECTS THE DISEASE EARLY BUT IT LEADS TO MODEST REDUCTION IN PROSTATE CANCER MORTALITY IF ANY, IF YOU COMPARE WITH PLCL OUTCOMES. WHEN WE WAIT FOR SYMPTOMS, MOST DIE OF THE DISEASE THIS AS YOU CAN SEE NUMBER OF SURVIVAL CURVES FROM SOME OF OUR ORIGINAL SOUTHWEST ONCOLOGY GROUP CLINICAL TRIALS, TRIAL STARTED IN THE '80s, IN THE '90s AND MORE RECENTLY. WITH P SA DETECTION YOU SEW EARLIER MODEST REDUCTION IN PROSTATE CANCER RISK LOOKING AT THE MOST OPTIMISTIC OUTCOMES FROM THE CLINICAL TRIAL FROM EUROPE. SO THE OPTIONS WITH REGARDS TO PROSTATE CANCER IF YOU ARE WORRYING YOUR PUBLIC HEALTH -- WEARING YOUR PUBLIC HEALTH HAT INCLUDES CUREING A DISEASE WHEN SYMPTOMATIC, WHEN SYMPTOMS PRESENT, BPH IS ALMOST NEVER ASSOCIATED WITH PROSTATE CANCER, WHEN SYMPTOMS PREVENT FROM THE DISEASE DEATH IS INEVITABLE. SCREENING FOR THE DISEASE WHICH LEADS TO SIGNIFICANT OVERTREATMENT, SIGNIFICANT SIDE EFFECTS AND I WOULD ARGUE DIVERTS PRECIOUS HEALTHCARE RESOURCES TOWARDS A VERY EXPENSIVE INTERVENTION, THE THIRD OPTION IS PREVENTION. THE ATTRACTIVE FEATURES OF PREVENTION FOR FEATURE IS MEDIAN AGE FOR DEATH IS 80, THE LAST TIME I REMEMBER TO LOOK AT IS THE AVERAGE LIFE YEARS LOST FROM PROSTATE CANCER IS NINE, AND SO IF YOU MAY NOT NECESSARILY PREVENT IT BUT DELAY IT, THE IMPACT ON MORTALITY COULD BE SUBSTANTIAL. SO THERE WAS A CONFLUENCE EVENTS IN 1990, '91, '92 A SIGNIFICANT SPIKE IN CANCER DIAGNOSES BECAUSE OF PSA TESTING, BECAME ADOPTED ROLLED OUT AND WIDELY DONE QUICKLY IN THE UNITED UNITED STATES, DIAGNOSING AND TREATING THE DISEASE AND FDA REGISTRATION OF -- THE FIRST FIVE ALPHA REDUCTASE INHIBITOR, PAUL LANES EDITORIAL IN NEW ENGLAND JOURNAL, HE ASKED THE QUESTION IS THE PROSTATE PILL HERE SUGGESTING WIDESPREAD USE OF THAT. AT THAT POINT IN TIME WE UNDERSTOOD TESTOSTERONE, SIMPLE BASICS OF THIS, TESTOSTERONE IS ACTED UPON BY FIVE ALPHA REDUCTASE TO FORM DHT WHICH HAS AN EIGHT FOLD GREATER AFFINITY FOR THE ANDROGEN RECEPTOR. THE DEVELOPMENT OF FIVE ALPHA REDUCTASE INHIBITORS IS SOMEWHAT SERENDIPITOUS AND TARGETED AND MAYBE ONE OF THE FIRST TARGETED PREVENTION STRATEGIES EVER DONE, MEN WITH MUTATION OF SRA TYPE 2 ENZYME MUTATION DON'T DEVELOP BPH OR PROSTATE CANCER, LOOK AT& THE MRI, RUDIMENTARY PROSTATE, THEY DON'T DEVELOP BPM FOR FOUR DECADES USED EFFECTIVELY AND FOUNDATION FOR MANAGEMENT OF PROSTATE CANCER IN A NUMBER OF STAGES. CLINICAL STUDIES FOUND IT EXTREMELY WELL TOLERATED AND LATER AS YOU ALL PROBABLY KNOW AS APPROVEED FROM THE TREATMENT OF MALE PATTERN BALDNESS USED IN YOUNGER MEN AND OLDER FOR MANAGEMENT OF BPH SO THIS CONFLUENCE PIPELINE OF EVENTS FOR BOARD OF SCIENTIFIC COUNSELORS, WHAT WAS CALLED DCPC AT THAT TIME IF I REMEMBER CORRECTLY, RECOMMENDED STUDY FOR PROSTATE CANCER PREVENTION AND EPIDEMIC OF PSA TESTING AS WELL AS DISCOVERY OF THE DRUG THAT SEEM TO PERHAPS HAVE A MOLECULAR BIOLOGIC RATIONALE FOR PREVENTION. WE WERE INVITED TO THE NCI BASEMENT OF THESE OLD EXECUTIVE PLAZA BUILDING TO DESIGN THE TRIAL. THE CHALLENGE WE FACE IS PRIMARY METHOD OF CANCER DIAGNOSIS PSA REDUCES PROSTATE CANCER PSA REDUCES BY ABOUT 50%. IF THE STUDY WERE THAT VERSUS PLACEBO HOW WOULD YOU ADJUST AS P ISS DROP THE SAME AND PEOPLE WITH PBH VERSUS PROSTATE CANCER AND ONLY ONE SOLUTION ABOUT TWO DAYS OF DISCUSSION IS BIOPSY ALL MEN AFTER SEVEN YEARS. SO THE FINAL SCHEME OF THE TRIAL WAS TO ENROLL AND WE ULTIMATELY ENROLL 24,000 MEN RANDOMIZING 19,000 MEN TO PLACEBO OR FINASTERITE, STANDARD OF CARE WAS ANNUAL PSA TESTING BUILT IN, IT WAS ADJUSTED SO THERE WAS AN EQUAL RISK OF BIOPSY IN ANNUAL BASIS FOR MEN AND END OF STUDY BIOPSY, IT WAS UNCERTAIN WHETHER MEN IN THE UNITED STATES COULD PARTICIPATE IN CANCER PREVENTION TRIAL. I REMEMBER COMING TO THE PRESS CLUB DOING THE PRESENTATION AND THAT NEXT DAY THE CANCER INFORMATION SERVICE RECEIVED THE MOST PHONE CALLS THEY HAD EVER RECEIVED AND IT WAS ONLY ECLIPSED BY THE FOLLOWING DAY WHERE YOU CAN SEE WHAT HAPPENED AT THE BEGINNING OF THIS TRIAL THE 200 SOME ODD SITES THAT WE HAD MANY OF THOSE SITES FILLED UP WITHIN A YEAR AND COMPLETED THEIR ACCRUAL IN A YEAR AND WE TAILED OFF DURING THE THREE YEARS OF ANTICIPATED ACCRUAL WE OVERACCRUALED FOR THE TRIAL. MEN WERE ACCRUED FOR ALL OVER THE UNITED STATES, TIP OF HAT TO PAUL GODLEY WHO CHAIRED, THANK YOU VERY MUCH, PAUL. YOU CAN SEE AT THE TEND OF THE TRIAL BIOPSIES COMING IN THERE WAS NOT A PLAN FOR EARLY INTERIM ANALYSIS BECAUSE BULK OF CANCER WERE ANTICIPATED AT THE END OF TRIAL, THOSE WERE BIOPSIES BECAUSE THE MEN BEGAN AT THE BEGINNING OF THE TRIAL. IN FEBRUARY OF 2003 WE WERE IN DALE LABS I WAS MEETING FOR A PO 11 MEETING, PAUL WALKED OVER AND SAID YOU ARE DONE. FERTILITY ANALYSES SHOWED MET THE END END POINT PROSTATE CANCER OVER SEVEN YEARS, IT PRODUCED THE RISK THE RELATIVE RISK REDUCTION WAS 25%. BUT LOOK AT THE CANCER RISK FAR EXCEEDED WHAT WE ANTICIPATED IN PART DUE TO THE END OF STUDY BIOPSY BUT ALSO FAR MORE CANCER WERE DETECTD THAN WE ANTICIPATED OVER THE COURSE OF THE TRIAL. THE RISK REDUCTION OCCURRED IN BOTH MEN THAT WERE DRIVEN FOR CAUSE WHICH WAS PSA OR REMEMBER TALL EXAM AS WELL AS A RISK REDUCTION IN MEN WITH END OF STUDY BIOPSIES WITH A NORMAL PSA. THER CHALLENGE WE FACE -- THE CHALLENGE WE FACED IS THIS, MAJORITY OF RISK REDUCTION OCCURRED IN THE GLEASON FIVE AND SIX, PREDOMINANT FORM OF THE DISEASE BUT THERE WAS SLIGHT INCREASE IN RISK OF GLEASON 8 THROUGH 10, ABOUT THE SAME NUMBER OF GLEASON 7 AND THOSE NOT PROSTATE CANCER AFICIONADOS THIS WAS THOUGHT TO BE AN INDOLENT DISEASE THOUGH WE HAVE NOW LEARNED IT PROBABLY IS NOT. AND 8 THROUGH 10 THE MORE LE TALL FORM. THE DSMC RELEASED DATA US TO RECOMMENDING TO END THE STUDY BECAUSE WE MET PRIMARY OBJECTIVE AND THE MOKOS AT THAT POINT IN TIME BECAUSE WE HAD MEN UNDERGOING END OF STUDY BIOPSIES UNNECESSARY, WAS TO CLOSE A TRIAL, GET THE DATA OUT, ANSWERING THIS PARADOX WOULD HAVE THE WAIT. -- WOULD HAVE TO WAIT. THAT WAS PUBLISHED IN NEW ENGLAND JOURNAL BUT ACCOMPANYING EDSTORIAL BY PETER SCARDINO WHO SAID IT SHOULDN'T BE USED SIMPLY BECAUSE OF THIS INCREASE RISK OF HIGH GRADE DISEASE. AS WE BEGIN TO LOOK AT THIS AFTER PAPERS CAME OUT WE BEGAN TO TRY TEASE OUT WHY WE HAD THIS PARADOX. I THINK HERE WE ARE 25 YEARS LATER HOPE TO BE ABLE TO PROVIDE YOU AN ANSWER TO THAT ALONG WITH JOE'S CRITICAL WORK IN THIS. TWO KINDS OF BIOPSIES OCCURRED DURING THE COURSE OF THE TRIAL. ONE WERE FOR CAUSE DRIVEN BY PSA AND RECTAL EXAM, OTHER WAS END OF STUDY BIOPSY. AND THE INTERESTING THING ABOUT THIS, IS THAT IF YOU ANTICIPATED THE FENESTERITE WAS ACTUALLY LEADING TO DEVELOPMENT OF CANCER OR HIGH GRADE CANCER YOU MIGHT HAVE EXPECTED IT TO CURVE LIKE THIS WITH P 1 TRIAL FOR ENDOMETRIAL CANCER OR ON THE RIGHT IF YOU WILL A DOSE RESPONSE FOR TOBACCO AND LUNG CANCER. IN A LETTER TO TEDTOR IN NEW ENGLAND JOURNAL, THE CURVES DIDN'T CHANGE OVER TIME, IT WAS ESTABLISHED RISK OF HIGH GRADE DISEASE YEAR ONE AND IT DIDN'T CHANGE MUCH OVER TIME. LEADING US -- THIS IS ONE OF THE PERHAPS TAKE HOME MESSAGES YOU DISCOVER THING YOU HADN'T THOUGHT ABOUT DOING THIS. IT'S A SIMPLISTIC NOTION TO DETERMINE ESPECIALLY IF YOU HAVE A HIGH PREVALENCE DISEASE WITH A RELATIVELY LOW RATE MORTALITY, TWO THINGS ARE NECESSARY TO DETERMINE PROSTATE CANCER PRESENT BECAUSE IT'S ASYMPTOMATIC AND UBIQUITOUS IN AGING MEN YOU FIRST MUST SUSPECT THE DISEASE. THEREFORE YOU HAVE TO HAVE AN ABNORMAL PSA OR RECTAL EXAM. THE OTHER THING THAT MUST HAPPEN IS YOU MUST THEN DIAGNOSE THE DISEASE. YOU HAVE TO RECOMMEND BIOPSY PATIENT HAS TO ACCEPT BIOPSY AND STRIKE LESION WITH YOUR BIOPSY NEEDLE. WE DIDN'T KNOW AS WE BEGAN THE TRIAL IT CHANGES ALL OF THOSE. IT'S SIGNIFICANTLY CHANGES THE PERFORMANCE CHARACTERISTICS OF PSA RECTAL EXAM AS WELL AS BIOLOGY SHY, THIS IS A FAMILY OF SEVER OPERATING CHARACTERISTIC CURVES FOR OVERALL CANCER, HIGH GRADE CANCER AND I WOULD CONTEND TO YOU THERE ARE A LOT OF BIOMARKERS THAT ARE BEING USED CLINICALLY THAT WOULD -- REGISTERED BASED ON THOSE KINDS OF RLC CURVES. IT IMPROVES SIGNIFICANTLY SENSITIVITY OF A INSENSITIVE TEST DIGITAL RECTAL EXAM, AND THE OTHER INTERESTING THING IS THAT BECAUSE IT ALSO CHANGES THE SIZE OF THE PROSTATE WE DO THE SAME NUMBER OF BUY I DON'T KNOW SIPS YOU HAVE -- BIOPSIES YOU HAVE A GREATER LIKELIHOOD IF CANCER PRESENT OF STRIKING WITH YOUR NEEDLE AND IT IMPROVES SENSITIVITY FOR DETECTION OF HIGH GRADE CANCER BY 40%. WE'RE ABLE TO DO THIS BECAUSE WE'RE TRACKING NOT ONLY BIOPSIES BUT THE RADICAL PROSTATECTOMIES AS WELL. FOLDING IT TOGETHER IN A ACCOUNTING FOR THESE BIASES THERE WERE SEVEN STUDIES SUBSEQUENTLY LOOKED AT THIS ACCOUNTING FOR BIASES AN CORRECTING FOR THOSE, THE ESTIMATE WAS THAT THERE WAS PROBABLY 30% OVERALL REDUCTION IN RISK OF CANCER, A GREATER RISK REDUCTION OF GLEASON SIX AND PERHAPS MAY HAVE LOST THAT REDUCTION AND INCREASE RISK OF GLEASON 7 THROUGH 10 IN FACT MARY REDMAN SUGGESTED RISK REDUCTION OF GLEASON 7 THROUGH 10. NONETHELESS THE STICKY FAT STUCK AND SPEAKING WITH FOLKS FROM THE MEDIA AFTERWARDS AS UPDATES CAME ALONG, THEY SAID OH, THAT'S THE TRIAL THAT SHOWED THAN IT CAUSES AGGRESSIVE PROSTATE CANCER. BIASES EXPLAIN SOME OF THESE HIGH GRADE CANCERS, WE WEREN'T CERTAIN, WE FIRST QUESTION WE ASKED WAS HOW DO SURVIVAL RATE DIFFER BETWEEN THE ARMS. WHAT HAPPENED WHEN STOPPED THE STUDY DRUG DID THE DIFFERENCE DISAPPEAR, MORE IMPORTANTLY THE MOST IMPORTANT THING AS BARRY POINTED OUT EARLIER, HERE WE HAVE A DRUG THAT ACTUALLY AFFECTS BPH FOR EXAMPLE, MALE PA TERM BALDNESS AND NUMBER OF OTHER BENEFIT BUS IF IT CAUSES THE DEVELOPMENT OF HIGH GRADE CANCER RISK OF DEATH FROM PROSTATE CANCER WOULD BE SIMPLY UP ACCEPTABLE AND PREVENTION STRATEGY. FIRST THING WE DID IS MAPPING THIS WITH THE SOCIAL SECURITY DEAF INDEX ASKING LONG TERM SURVIVAL IN 2013, FIVE YEARS AGO, AND ALSO BECAUSE DATA DATA WERE LOCKED IN MAY OF 2003, WE CONTINUED THE END OF STUDY BUY I DON'T KNOW IS IS UNTIL OCTOBER OF -- BIOPSY UNTIL OCTOBER OF THAT YEAR, UPDATED TOTAL NUMBER OF CANCER AND RISK REDUCTION WITH UPDATE, BIASES OPERATIONAL BECAUSE SOME OF THE MEN MAY HAVE BEEN UNBLINDED, 30% RISK REDUCTION, YOU SEE INCREASE RISK OF HIGH GRADE DISEASE BUT WAS NO LONGER PRESENT BUT MOST IMPORTANTLY, WE SAW THAT THE OVERALL SURVIVAL OF BOTH ARMS WAS IDENTICAL. THE CANCER DIAGNOSIS IN THAT AND THE PLACEBO ARM, THEY WERE SUPERIMPOSABLE SUGGESTING THAT WE WERE IN GOOD SHAPE. WITH THAT WHAT I WOULD LIKE TO DO IS TAG TEAM, JOE WILL TAKE OVER NOW. AND TAKE YOU THROUGH HOW WE ARE ABLE TO CONTINUE THE USE THIS ANALYSIS. >> THANK YOU VERY MUCH FOR HAVING ME TODAY AND THANK YOU, IAN. SO I WANT TO TOUCH ON WORK WE HAVE DONE THAT PERTAINS TO THE INTERSECTION OF TWO DOMAINS DR. SHARPLESS MENTIONED WHICH ARE BIG DATA STRATEGIES AND CONDUCT OF CANCER CLINICAL TRIALS. AS MANY OF YOU KNOW BIG DATA IS CHARACTERIZED PERTAINING NOT JUST VOLUME WHICH IS TYPICALLY THE WAY IT'S REGARDED BUT ALSO WITH REGARD TOP VELOCITY AND VARIETY OF DATA. WE EMPHASIZED VARIETY OF BIG DATA IN BIG DATA ANALYSIS USING LARGE NCI NETWORK NATIONAL CLINICAL TRIALS DATABASE IN COMBINATION WITH DATA SOURCES AS SERE REGISTRY DATA, GEOSPATIAL DATA OR MEDICARE CLAIMS WHICH I WILL GET TO. HERE IS AN EXAMPLE OF USING BIG DATA STRATEGIES TO EXAMINE TREATMENT OUTCOMES, WE EXAMINE SURVIVAL PATIENTS FOR RURAL PATIENTS WITH CANCER TREAT IN CLINICAL TRIALS BY COMBINING TREATMENT TRIAL DATA WITH GEOSPATIAL MAPPING DATA. WE EXAMINED 37,000 PATIENTS FROM 44 PHASE 3 TREATMENT TRIALS WHICH WE STACK TOGETHER FROM ALL 50 STATES. THE MAP SHOWS RURAL PATIENTS IN THE RED DOTS IN URBAN PATIENTS AND BLACK DOTS. WHAT WHAT WE FOUND IS RURAL PATIENTS HAD WORSE SURVIVAL IN NEARLY ONE OUT OF 17 CANCER COHORTS, THAT WE CONSTRUCTED. THIS SUGGESTED A BEST APPROACH OR ONE GOOD APPROACH TO IMPROVING OUTCOMES FOR RURAL CANCER PATIENTS MAYBE PERHAPS TO ENROLL IN CLINICAL TRIALS BUT ALSO TO PROVIDE ACCESS TO THE KIND OF QUALITY GUIDELINE BASED CARE THAT IS AVAILABLE IN TRIALS. SO PIVOTING BACK TO PCT, SOME LIPPING ARE QUESTIONS ONE WHICH IS IT IS UNCLEAR IF TRIAL DURATION WAS SUFFICIENT TO DETERMINE THE MAXIMUM BENEFIT OF FIN, ASTERIDE ANOTHER -- ONE CONCERN WAS REDUCED RISK OF PROSTATE CANCER SEEN IN SUBJECTS RECEIVING FINASTRIDE MAY IN THE BE MAINTAINED AFTER DISCONTINUATION. THESE -- THIS QUESTION THESE QUESTIONS CANNOT BE ADDRESSED USING CLINICAL STUDY DATA ALONE BECAUSE FOLLOW-UP TERMINATED AT SEVEN YEARS AND NO ADVERSE EVENT COLLECTED AFTER TREATMENT STOPPED AND THERE WAS LIMITED UTILIZATION DATA BEYOND PROTOCOL SPECIFIED THERAPY. SO PROGRAM OBJECTIVES OF PCPT LINKAGE TO MEDICARE CLAIMS MORE BROADLY LINKAGE TO MEDICARE CLAIMS WAS TO LINK TRIAL RECORDS TO MEDICARE CLAIMS TO EXAMINE LATE EFFECTS LONG TERM PROSTATE CANCER DIAGNOSES, TREATMENT UTILIZATION AND COMPLICATIONS. YOU CAN SEE HERE THAT THE ADVANTAGES BROUGHT BY THIS APPROACH ARE SYNCHRONOUS, CLINICAL TRIALS PROVIDE SASS SAME BASELINE CRIMINAL FACTOR DATA IN THE ON STUDY OF PROSTATE CANCER DIAGNOSES WHILE MEDICARE CLAIMS PROVIDE LONG TERM FOLLOW-UP FOR OTHER ILLNESS, NEW CANCER DIAGNOSES OVER THE LONG TERM AN TREATMENT UTILIZATION. OF COURSE IN THE RANDOMIZE SETTING IF YOU HAVE RANDOM ASSIGNMENT YOU RETAIN ADVANTAGE OF RANDOMIZATION BY LIMITING CONFOUNDING. SO THE QUESTION WAS, WHAT ARE THE PATTERNS OF LONG TERM PROSTATE CANCER DIAGNOSES IN THE PREVENTION TRIAL. WE HAD TO DEFINE A MEDICARE CLAIMS BASED PROSTATE CANCER DIAGNOSIS ALGORITHM IN ORDER TO DO THIS, WE CREASED DIAGNOSIS AND PROCEDURE CODES FROM MED KALE CLAIMS AND -- MEDICARE CLAIMS, MEN WERE INCLUDED BECAUSE THEY WERE CONSIDERED AT RISK OF PROSTATE CANCER. INCLUDING THOSE WITHOUT MEDICARE LINKAGE. ONE COMPLICATION IS THE PCPT ENROLLED PATIENTS FROM 1997 TO '97, WHEREAS MEDICARE CLAIMS DATA WERE AVAILABLE FROM 1999 TO 2011, '99 BEING EARLIEST AVAILABLE FOR RESEARCHERS UNLESS I'M CORRECTED, THAT IS MY UNDERSTANDING. THIS PRESENTED ANALYTICAL CHALLENGES. NONETHELESS WE EXAMINED IN THIS CONTEXT MULTIPLE CLAIMS BASED ALGORITHMS, CONSIDERING THE PROSTATE CANCER DIAGNOSIS WHILE ON THE PCPT AS THE FOLD STANDARD -- GOLD STANDARD COLLECTED UNDER BEST PRACTICES IN A CLINICAL TRIAL SETTING. FROM WE COMPARED PCPT TO MEDICARE DIAGNOSES AMONG MEN WITH CONCURRENT COVERAGE IN BOTH PCPT AND MEDICARE -- AT THE SAME TIME THEY HAD MEDICARE COVERAGE. SO THIS OVERLAP REGION IS REALLY CRITICAL FOR VALIDATING CLAIMS BASED APPROACH TO EVENT IDENTIFICATION BECAUSE THE -- YOU HAVE THE GOLD STANDARD AND YOU CAN USE THAT TO VALIDATE AN ALGORITHM FOR MEDICARE CLAIMS. THE BEST ONE WE IDENTIFIED IS HAVING AN ICD 9 DIAGNOSIS CODE OF 185 FOR PROSTATE CANCER, FOR ANY HOSPITAL CLAIM OR TWO OR MORE PHYSICIAN OR OUTPATIENT CLAIMS GREATER THAN 30 DAYS APART APPROACH COMMONLY USED. WE SET A CAP OF NO MORE THAN SIX MONTHS APART. IN ORDER THE RULE OUT ICD 9 PROSTATE CANCER CODE FOR ANNUAL SCREENINGS. WE INCLUDED ANY RADICAL PROSTATECTOMY AS BEING DEFINED AS A PROSTATE CANCER DIAGNOSIS. WITH THIS APPROACH WE HAD A SENSITIVITY OF 83% AND SPECIFICITY OF 96% WHICH IS FAIRLY GOOD. WEIUS THIS APPROACH TO EXAMINE CUMULATIVE INCIDENTS AT FIVE, TEN, 15 YEARS AFTER RANDOMIZATION KEEPING IN MIND THE PCPT ENDED AT SEVEN YEARS. COX REDEPRESSION WAS USED TO TEST THE INTERVENTION -- REGRESSION WAS USED AND IT IS WORTH NOTING AS IAN MENTIONED, END OF STUDY BIOPSY AT SEVEN YEARS WHICH MEANT LARGE PROPORTION OF CASES IDENTIFIED AT SEVEN YEARS, TO ACCOUNT FOR THIS WE USED AD CHANGE POINT ANALYSIS WHERE WE SET UP THREE REGIONS OF FOLLOW-UP FROM 0 TO 6.5 YEARS ONE YEAR AROUND THAT SEVEN YEAR END OF STUDY BIOPSY TIME OF 6.5 TO 7.5 YEARS, AFTER 7.5 YEARS EXAMINE INTERVENTION EFFECT WITHIN THOSE REGIONS SEPARATELY. IN TOTAL WE HAD A SUCCESSFUL MEDICARE LINKAGE TO THREE OF FOUR PATIENTS. 14,176 IN TOTAL. FROM MS.SUBJECT CHARACTERISTICS WERE WELL BALANCED BY ARM AND MEDIAN TIME FROM PCPT RANDOMIZATION TO END OF OBSERVE VISION FOR ALL PATIENTS INCLUDING THAT MEDICARE COVERAGE LINKAGE WAS 16 YEARS WHICH WAS A NINE YEAR INCREASE OVER FOLLOW-UP USING THE CLINICAL STUDY ALONE. WE CAN SEE HERE IN THIS TABLE MEDICARE ALONE DIAGNOSES WERE A THOUSAND -- NEARLY A THOUSAND ADDITIONAL PROSTATE CANCER IDENTIFIED USING THAT MEDICARE LINKAGE. THESE WERE DIAGNOSES THAT WERE NOT OTHERWISE CAPTURED BY THE PCPT CLINICAL RECORDS. THIS IS HERE THE TAKE HOME MESSAGE, THE TAKE HOME SLIDE, THE CUMULATIVE INCIDENCE USING THE PCPT CLINICAL RECORDS ALONE OF PROSTATE CANCER, FOR THE PLACEBO FINESTEIDE ARMS THROUGH 7.5 YEARS, DASH LINES INDICATE CRITICAL REGION AROUND THAT SEVEN YEAR BIOPSY TIME YOU CAN SEE THERE WAS A HUGE SPIKE IN THE NUMBER OF DIAGNOSES. WHEN WE ADD IN THAT MEDICARE LINKAGE, THIS ALLOWED US TO EXTEND WAY OUT TO 16 YEARS MEDIAN AND MAXIMUM OF 18 YEARS. YOU CAN SEE HERE THE CURVES WHICH IS INTERESTING, NEITHER COME TOGETHER NOR CONTINUE TO SEPARATE. THERE'S NO TAILING OFF. SO THIS SLIDE HERE REPRESENTS SUMMARIZES THOSE FINDINGS. THIS IS A FOREST PLOT OF THE HAZARD RATIO OF PROSTATE CANCER, SOLID VERTICAL LINE IN THE MIDDLE IS EQUAL HAZARD. AND AND BOXES ARE THE HAZARD RATIOS AND HORIZONTAL LINE ABOUT THEM ARE THE 95% CONFIDENCE INTERVALS SO YOU CAN SEE FROM 0 TO 7.5 YEARS THERE WAS 29% RISK REDUCTION TO DUE TO FINASTERIDE CONSISTENT WITH THE FINDINGS. AFTER # .5 YEARS THERE WAS NO SIGNIFICANT DIFFERENCE FOR THAT VERSUS PLACEBO ARM PATIENTS IN TERMS OF THEIR PROSTATE CANCER DIAGNOSES WITH THE 95% CONFIDENCE INTERVAL INCLUDING LINE EQUAL HAZARD. OVERALL THROUGH THAT 16 YEARS THERE WAS A 21% RISK REDUCTION IN TERMS OF PROSTATE CANCER DIAGNOSIS. WE EXAMINE ISSUES TO GET AT POTENTIAL BIAS ASSESSMENT THE USE OF ADMINISTRATIVE CLAIMS INTRODUCE BIAS IN TERMS OF DETECTION OF PROSTATE CANCER THAT COULD INFORM THE INFERENCE BY ARM, WE EXAMINE UTILIZATION PATTERNS HAVINGS PLACEBO AND NO DIFFERENCE IN SCREENING CLAIMS BY ARM NO DIFFERENCES IN HOSPITAL IN PATIENT OR PHYSICIAN OUTPATIENT VISITS AND NO DIFFERENCES IN IN OVERALL CLAIMS. FROM NO DIFFERENCES IN UTILIZATION PATTERNS, THERE WAS ALSO NO DIFFERENCES IN DIAGNOSIS STATES BY ARM. THERE ARE ALSO NO DIFFERENCES IN BASELINE DEMOGRAPHIC AND CLINICAL RISK FACTORS ALL THESE CONSIDERATIONS IMPROVE OUR CONVERSATION IN THIS -- CONFIDENCE IN THIS FINDING. SO IN SUMMARY, THERE WAS NO EVIDENCE THAT SEVEN YEARS OF FINESTERIDE CONTINUED TO PREVENT CANCER DIAGNOSES AFTER DISCONTINUATION. BUT ALSO NO OTHER EVIDENCE IT HAD MORE PROSTATE CANCER OR USE LED TO MORE DIAGNOSIS OF CANCER AFTER COMPLETING FINESTRIDE. OVER 16 YEARS IT PROVIDED SUBSTANTIAL 21% REDUCTION OF PROSTATE CANCER. I WANT TO DIGRESS EDITORIALIZE FOR A SECOND. BY TALKING ABOUT THE USE OF SECONDARY DATA FOR CLINICAL TRIAL FOLLOW-UP CANCER PREVENTION TRIALS AS IAN INDICATED FOLLOWING A LARGE NUMBER OF PARTICIPANTS FROM MANY YEARS AND CONDUCTING THESE TRIALS IS COSTLY, THE USE OF SECONDARY DATA SOURCES COULD AUGMENT THE DETECTION OF LONG TERM OUTCOMES AT MUCH REDUCED COST WHICH IS AS WE SHOWED WITH THIS EXAMPLE, IN GENERAL BIG DATA STRATEGIES USED TO EXTEND AND ENRICH VALUABLE NCTN AND N CORPS CLINICAL TRIAL DATA BY EXTENDING FOLLOW-UP OR DATA COLLECTION FOR INDIVIDUAL TRIALS OR BY INCLUDING THEM IN SECONDARY DATA ANALYSES BY COMBINING DATA FROM MULTIPLE TRIALS AND I THINK THIS APPROACH WOULD BE ESPECIALLY ADVANTAGEOUS IN DISEASE SETTINGS WITH RARE OR LONG TERM EVENTS INCLUDING PREVENTION OR ADJUVANT TREATMENT. WITH THAT I'M TURNING BACK TO IAN. >> THANK YOU, JOE. OBVIOUSLY THE QUESTION STILL REMAINS ABOUT HIGH GRADE DISEASE AND POTENTIAL RISK OF HIGHER CANCER MORTALITY AND MORTALITY OBVIOUSLY IS THE PRINCIPAL OUTCOME THOUGH DIAGNOSIS OF A NON-LETHAL PROSTATE CANCER LEADS TO NUMBER OF ADVERSE CONSEQUENCES TO THE BARER OF THAT DIAGNOSIS. SO TO BE ABLE TO ANSWER THAT QUESTION WE USED A LINKAGE ANALYSIS INCLUDING SOCIAL SECURITY NUMBERS COLLECTED IN THE VAST MAJORITY OF PCP TO PARTICIPANTS AND THEY WERE MATCHD WITH THE U.S. NATIONAL DEATH INDEX. THE FIRST MATCHING WAS WITH THE SOCIAL SECURITY DEATH INDEX. THIS IS THE NDI STUDY FOR THREE OUTCOMES, DEATH, DEATH DUE TO PROSTATE CANCER AND THAT WAS MADE BASED ON DEATH CERTIFICATE. ULTIMATELY AS YOU CAN SEE HERE, HERE IS THE TABLE U SEE THE PROSTATE CANCER DEATH, 56 IN PLACEBO, 42 IN FINASTRIDE TOTAL NUMBER OF PERSON YEARS FOLLOW-UP WAS 300,000 PERSON YEARS OF FOLLOW-UPMENT I POINT OUT SEVERAL THINGS THAT ARE STILL HEAD SCRATCHERS AT THIS POINT IN TIME, THIS IS UNPUBLISHED DATA. BUT IF YOU LOOK AT FOR EXAMPLE GLEASON SCORES OF THE INDIVIDUALS WHO DIED OF PROSTATE CANCER, A THIRD OF THE MEN WHO DIED OF PROSTATE CANCER HAD GLEASON SCORES OF SIX OR LESS. OTHERWISE THOUGHT TO BE INDOLENT DISEASE. THE OTHER THING OF INTEREST IS INDIVIDUALS WITH RELATIVELY LOW PSAs, AT THE TIME OF DIAGNOSIS CONSTITUTE THIRD OF CANCER DEATH AND NUMBER OF DEATH DUE TO PROSTATE CANCER THAT WERE PROMMED BY END OF STUDY BIOPSIES OR FOR CAUSE WERE ABOUT THE SAME. AGAIN, POINTING OUT TO US THAT THERE ARE DATA WE COLLECT FROM THIS THAT WERE OTHERWISE UNEXPECTED. IF YOU LOOK AT THE LONG TERM RISK OF PROSTATE CANCER DEATH IN TWO ARMS OF THE STUDY, THERE IS NO EVIDENCE OF ANY INCREASE, THERE IS A REDUCTION IN RISK OF DEATH FROM PROSTATE CANCER WITH FINESTRIDE BUT BECAUSE OF THE SMALL NUMBER OF DEATHS IT IS NOT STATISTICALLY SIGNIFICANT. WHEN THIS STUDY RAN OUT OR BEGAN, THE DRUG WAS NOT GENERIC, IT HAS BEEN GENERIC FOR MANY, MANY YEARS. AND THE COST FULL FREIGHT OF PHARMACY IS 25 CENTS A DAY, MY PHARMACIST AND HOSPITAL SYSTEM SAYS IF YOU GET A GOOD DEAL IT'S PENNY A PILL. SO IN TERMS OF A PREVENTION STRATEGY THAT'S COST EFFECTIVE, IT'S PRETTY GOOD. SO WHEN YOU THINK ABOUT CHEMOPREVENTION WITH AN AGENT LIKE FINETRIDE AFTER 20 YEARS REDUCES THE RISK OF PROSTATE CANCER BETWEEN 25 AND 30%, WHAT HAPPENS IF YOU TAKE LONGER WE DON'T KNOW. IN THE FACE OF IMPROVED PROSTATE CANCER DECK. THE DRUG BIASES YOU TOWARDS DICTION OF PROSTATE CANCER, AS WELL AS BIASES TOWARDS DETECTION OF HIGH GRADE DISEASE, REDUCTION IN RISK AS JOE POINTED OUT FROM HIS LINKAGE IS DURABLE. MOST ARE PREVENTED GLEASON 3 PLUS 3 AND RISK OF PROSTATE CANCER DEATH IS LESS BUT NOT STATISTICALLY SIGNIFICANT. THE PROS TO THIS ARE THE RISK OF REDUCTION AND DIAGNOSIS AND THEREFORE WOULD LIKELY, I'LL MENTION THIS IN A MOMENT WOULD TRANSLATE TO FEWER NUMBER OF PATIENTS HAVING SURGERY, RADIATION, OR TREATMENT COMPLICATIONS. THERE APPEARS NO ACCESSORIESK OF PROSTATE CANCER DEATH. AS BARRY POINTED OUT ASPIRIN IS ANSWER THE EVERYTHING, URINE RETENTION REQUIRING TUR OF PROSTATE REDUCING THE RISK OF URINARY TRACT INFECTIONS OR OTHER TREATMENTS FROM UBIQUITOUS DISEASE OF AGING MEN BPH AND EXPENSIVE, THE CONS THERE ARE ALWAYS CONS IS THAT THERE'S A SMALL BUT SIGNIFICANTLY INCREASED RISK OF SEXUAL SIDE EFFECTS AND (INDISCERNIBLE) BECAUSE OF IT LEADS TO ABOUT A 10% INCREASE IN SERUM TESTOSTERONE TO A SLIGHT INCREASE IN RICKS OF GYNOCOMASTIA. AS A COMMENTARY IN PREVENTION FOR TUMORS MAY HAVE LOWER LESS THAN NATURAL HISTORY IS THAT SOME WOULD POSIT THESE TUMORS THAT ARE PREVENTED ARE INCONSEQUENTIAL LIKE POINT OUT TO YOU THAT A THIRD OF THE DEATH DUE TO THESE THOUGHT INCONSEQUENTIAL TUMORS, FOR THOSE WHO MANAGE THOSE PATIENTS IS A LIFE CHANGING EVEN. THERE IS 30 TO 50% RISK WITH SIDE EFFECTS, REPEATED VISITS, ANXIETY, REPEATED BIOPSIES THAT ARE EXPENSIVE AND CAUSE SEPSIS AND WITH ADVENT OF MRI AND OTHER IMAGING TECHNOLOGIES INCREASING THE RISK OF FURTHER DIAGNOSIS, ICER LOOKED THAT THE AND SAID SURVEILLANCE IS AS EXPENSIVE AS 38% RISK OF PROSTATE CANCER DEATH WERE GLEASON 3 PLUS 3 AND ALMOST 50% PROSTATE CANCER DEATH MEN WITH NORMAL P SA AND RECTAL EXAM TS. SO THERE IS A FINAL CHAPTER. THAT IS THE PIN ULTIMATE DATA PROSTATE CANCER SPECIFIC MORTALITY RISK AND THE FINAL CHAPTER FOR NOW IS THAT JOANNE AT THIS PATIENTS HE AND COLLEAGUES WILL LINK WITH OTHER OUTCOMES WE CAN FIND WITH CMS DATA. THOSE ARE RELATED TO FACT IF YOU ARE NOT DIAGNOSED WITH A PROSTATE CANCER YOU WON'T GET TREATMENT NOR HAVE SIDE EFFECTS OF THAT. THE INITIAL OUTCOMES WE LOOK AT WILL INCLUDE RADIATION PROBING TIETIS,SIS TIES AT THIS, -- PROBING TOE TIETIS, PLACEMENT OF ARTIFICIAL URINARY SPHINCTERS, PROS THESES, INCISIONS SUCK STRICTURES, ET CETERA, ET CETERA T. SO PEOPLE DESERVE CREDIT FOR THIS WORKS, HUNDREDS OF INVESTIGATOR IT IS RESEARCH ASSOCIATES, PICTURES THAT I WOULD LIKE TO POINT OUT TO YOU DOWN HERE. THERE'S PETER GREENWALD, BARRY, LORI IN THE BACK AND OTHERS MIKE LEBLANC THAT RUNS STATISTICAL CENTER AT SOUTHWEST ONCOLOGY GROUP BUT THE HEROS ARE PEOPLE WHO CARE DISEASE PREVENTION. I WOULD LIKE TO TAKE YOU BACK TO 1992, 1993 WHEN 24,000 MEN THOSE ARE MEN RANDOMIZED, 24,000 CARED ENOUGH ABOUT CANCER PREVENTION, TO SAY I'LL TAKE A PILL EVERY DAY, COME TO BE -- BE PHONE CALLED EVERY THREE MONTHS, COME TO SEE YOU EVERY SIX MONTHS, I'LL HAVE PSA DRAWN EVERY YEAR, AT THE END OF THE STUDY, TO HELP US IN THIS ROOM I'LL HAVE A BIOPSY, EVEN IF MY PSA IS ONE TO ANSWER THAT QUESTION AND PERHAPS DURING THE DISCUSSION WE CAN TALK ABOUT THE ALL THE OTHER INFORMATION THAT IS COME UP FROM THAT. SO WE GO TO QUESTIONS? >> GO AT THE END OF THE TABLE AND MAKE THIS A PSEUDOPANEL DISCUSSION. BARRY, IF YOU CAN JOIN TOO. THREE CHAIRS ARE THERE. PART OF THIS, THE DISCUSSION BASICALLY IS A LESSONS LEARNED IF YOU WILL. THIS WAS A NOBLE EFFORT THE NEXT COUPLE OF SPEAKERS WILL TALK PIPELINE OF THE DRUGS AND FUTURE DIRECTIONS. SO PART OF THIS I THINK IS FROM THIS PERSPECTIVE, WE'LL TRY IT IN 15 MINUTES, SOME OF THE LESSONS LEARNED. -- WAS ALSO ON THIS INVOLVED WITH THIS, I DON'T KNOW IF YOU WANT TO LEAD OFF WITH COMMENTS? >> THANK YOU, YES. THIS IS VERY IMPRESSIVE WORK. VERY PERSISTENT WORK ON A STUDY THAT TOOK PLACE A WHILE AGO. I AGREE, I THINK IT WILL HAVE IMPLICATIONS FOR PREVENTION STUDIES THAT DO REQUIRE SOMETIMES EXTENSIVE FOLLOW-UP WITH OUTCOMES OCCURRING OVER DECADES, POTENTIALLY DECADES OVER THE INTERVENTION. ONE OF THE THINGS I WAS INTERESTED IN LISTENING TO THE PRESENTATION, PARTICULARLY FOR DR. THOMPSON, THESE FINDINGS OF DURABLE AFFECT FROM FINESTERIDE ARE LIKELY OUTSIDE YOUR 95% CONFIDENCE INTERVALS, WHAT YOU ANTICIPATED WHEN THE STUDY STARTED. CURIOUS WHETHER THIS GIVES YOU PAUSE WHEN FINDING SOMETHING SO MUCH MORE ROBUST THAN YOU PROBABLY ANTICIPATED WHEN THE TRIAL STARTED. >> THE MAGNITUDE OF RISK REDUCTION IS EXACTLY WHAT POLYAND PLUME STEIN WROTE IN THE ORIGINAL TRIAL. THIS SPEAKS TO THE ISSUE OF BIOMARKERS SCREENING WE DIDN'T REALIZE THAT THE UBIQUITOUS DISEASE WE KNOW EXISTS AT -- ON AUTOPSY STUDIES IN THE PROSTATE YOU CAN FIND WITH SIMPLY PUTTING SIX NEEDLESS IN A PROSTATE. SO IT WAS THE MAGNITUDE OF THE RISK REDUCTION WAS MY RECOLLECTION ALMOST EXACTLY WHAT WAS IN THE ORIGINAL PROTOCOL BUT IT WAS THE SHEER LIKELIHOOD RISK OF DIAGNOSIS WAS FOUR FOLD GREATER THAN ANTICIPATED. NOT SURE IF I'M ANSWERING YOUR QUESTION, WHETHER THE CURVES COME BACK TOGETHER AGAIN. >> DID YOU ANTICIPATE DURATION OF EFFECT THE WAY IT'S PANNING OUT? >> NO. THERE'S SO MANY MORE BIOLOGIC QUESTIONS THAT HAVE TO BE ADDRESSED THAT COULD BE ADDRESSED WITH REGARDS TO THAT. >> SPECTACULAR WORK, IT'S A TESTAMENT TO WHAT YOU HAVE DONE OVER TIME. ONE THING I DID LEARN FROM DR. KRAMER YEARS AGO, SOMETIMES IT'S DIFFICULT TO LINK DISEASE SPECIFIC MORTALITY WITH -- BECAUSE IT'S MEDICAL RESIDENTS RUNNING DOWN PROSTATE CANCER DEATH BECAUSE OF PSA. ANY DATA ON OVERALL MORTALITY AMONG POPULATIONS? >> THAT WAS THE PAPER IN NEW ENGLAND JOURNAL FROM 2013 THAT SHOWED MORTALITY THE SAME. IT EMPHASIZES -- REALLY HAS TO DO WITH WHAT ARE WE TRYING TO DO WITH DISEASE PREVENTION? IT EMPHASIZES THIS IS A DRUG THAT DOESN'T REDUCE THE RISK OF PROSTATE CANCER MORTALITY, IT REDUCES YOUR LIKELIHOOD, OVERALL SURVIVAL IS THE SAME. IN THE ORIGINAL TRIAL DESIGN OUR ORIGINAL PROTOCOL WE HAD A VARIETY OF END POINTS AND VARIETY OF DESIGNS WE HAD TO THROW UP FOR VARIETY OF REASONS. ONE WHICH WAS OVERALL MORTALITY, PROSTATE CANCER IS SUCH A LOW TO THE INDIVIDUAL IT AFFECTS IS HIGH BUT AS POPULATION IT'S 3%. YOU NEED 100,000 MEN FOR 25 YEARS FOLLOW-UP TO ANSWER THAT QUESTION. YOU CAN'T GET OVERALL WHICH IS WHY AS YOU EXPECT THE OVERALL SURVIVAL IS THE SAME. TO THE INDIVIDUAL PERSON, NOT GOING TO CALL IT A PATIENT TO THE SUBJECT AND THE TRIAL, A DIAGNOSIS OF CANCER IS A BAD THING, ANY CANCER NOT JUST PROSTATE AND TO TRIVIALIZE A CANCER DIAGNOSIS IS SO TO IGNORE THE FEELINGS AND IMPACT ON A PATIENT. WHAT WE FIND OUT IS NOT AFFECTING MORTALITY, WE'RE NOT ADVERSELY AFFECTING MORTALITY, WE'RE ELIMINATING THE DIAGNOSIS AND CONSEQUENCES OF CANCER DIAGNOSIS AND FREQUENT CANCER DIAGNOSIS. >> FOLLOW-UP, AS YOU MENTIONED SIX BIOPSIES 20, 30 YEARS AGO NOW WITH MRI SCREENING DIRECT DETECTION IS DIFFERENT. SO TWO QUESTIONS, FIRST GLEASON SIX FROM BIOPSIES THAT YOU TALKED ABOUT? >> THEY WERE BIOPSIES, THAN CENTRALLY READ BY GARY MILLER. UNTIL ABOUT A YEAR INTO IT WHEN HE PASSED AWAY. AND SCOTT LUCIA PICKED UP SO ALL OF THOSE ARE CENTRALLY READ. THE PROSTATECTOMY FOR THAT UPGRADING BIOPSY GREATER LIKELIHOOD OF DIAGNOSING, THAT WAS COMPARING BIOPSIES WITH THE PROSTATECTOMY, ALSO CENTRALLY READ. >> ANY THOUGHTS HOW THE USE OF IMAGING, HARD TO PREDICT BUT OBVIOUSLY CHANGE THESE OUTCOMES? SPECULATIVE BUT LOOKING MRI WE'RE GOING TO FIND MORE CANCER FOR SURE. >> WE WERE GOING TO FIND MORE CANCER, BARRY WAS JUST TALKING ABOUT THAT. MY LOOK AT THIS IS IT WILL TAKE EVERYTHING ON THE NOTCH. THE CHALLENGE WE FACE IN THIS IS THAT YOU DO MORE BIOPSIES, IF YOU FIND GLEASON INTERNALLY REVIEW THREE PLUS THREE TUMORS, THE KAPPA FOR A GLEASON DIAGNOSIS OF 3 PLUS 3 IS .7. IF U YOU ADD MORE INTO THE MIX, YOU WILL DRIVE UP THE NUMBER OF INTERMEDIATE GRADE TUMORS TREATED WITH THE CONSEQUENCES THEREOF. >> SO I WANT TO APPLAUD THE USE OF OTHER DATE BASES AND INTEGRATING THIS PROJECT TO ANSWER QUESTIONS AN QUESTIONS WE DEN KNOW WE WOULD HAVE AT THE TIME, PCPT WAS DEVELOPED. IS THERE -- MAYBE YOU HAVE DONE IT AND I'M NOT AWARE, CAN BE USE SUCH DATA TO ANSWER THOSE BIOLOGIC QUESTIONS SUCH AS I'M CURIOUS WAS THE RISK REDUCTION EQUAL AMONG PARTICIPANTS, ARE THERE PERSONALIZED RISK FACTORS THAT YOU CAN PULL OUT OF THAT DATA TO UNDERSTAND WHO IS -- WHO WILL BENEFIT MORE FROM FINASTERIDE VERSUS OTHERS AND SECOND LOOK AT WHAT MAKES THE THREE PLUS THREE TUMORS LOW THAT WILL IN BY INCORPORATING OTHER DATABASES TO BE ABLE TO LOOK AT THOSE QUESTIONS. >> WE START, JOE CAN GIVE YOU THE BETTER ANSWER TO IT. SO WE LOOKED AT A NUMBER OF ORIGINAL PATIENT CHARACTERISTICS THAT WE ALSO HAVE -- AN APPEAL A NUMBER OF OTHER ANALYSES THAT HAVE GIVEN SUGGESTIONS WHO MIGHT BENEFIT MORE. BUT IN THE GENERAL, EVERY SINGLE CHARACTERISTIC OF INDIVIDUALS BE IT FAMILY HISTORY, AGE, RACE ETHNICITY, ORIGINAL PSA ALL THE SORTS OF THINGS THAT BETHINK INCREASE RISK OF INDIVIDUAL MITIGATE THE RISK, RISK REDUCTION IS ALL 20 TO 30% RANGE >> I WANT TO COME BACK TO THE DIAGNOSIS -- >> WE ARE GOING TO DO GWAS STUDIES ON THESE. SO THAT -- WHEN WE CAN LINK THAT TO CLAIMS DATA TOO. SO WE HAVE MULTIPLE INDEPENDENT DATA SOURCES WE CAN USE TO ANSWER THESE QUESTIONS. >> I WANT TO COME BACK TO THE DIAGNOSIS QUESTIONS THAT WAS RAISED EARLIER WITH A SLIGHTLY DIFFERENT PLAY. AND I WANT TO PITCH SAMPLING ERROR YOU HAVE A SURPRISING RATE DIFFERENCE IN BIOPSY AND TURNED AROUND AND YOU GOT SURPRISING SURVIVAL DIFFERENCE NOT CONCORDANT WITH THAT GRADE. ONE WAY OF EXPLAINING THAT IS BIOLOGIC EFFECT AND THE OTHER WAY IS WE HAVE A LOT OF SAMPLING ERROR IN PROCESS. SO WE THINK ABOUT SAMPLING TECHNIQUES WITH IMAGING AND OTHER APPROACHES, IN ADDITION THE FINDING MORE TUMORS AND GETTING IN THE RIGHT PORTION OF THE PROCESS OF MALIGNANT RATHER THIS THAN BENIGN, SEEMS TO ME THE OTHER THING THAT'S IMPORTANT IS GETTING TO THE MOST MALIGNANT PART OF THE TUMOR WHEN YOU'RE DOING SAMPLES. I'M WONDERING IF YOU CAN COME COMMENT ON EXTENT WHICH YOU KNOW OR DON'T KNOW HOW MUCH ROLE SAMPLING ERROR PLAYED. >> PICK UP ON THE SAMPLING ERROR BASED ON NUMBER OF TUMORS THAT WERE UPGRADED AT RADICAL PROSTATECTOMY WE PUBLISHED ON. THAT IS AN UNANSWERABLE QUESTION. I THINK YOU NEED TO TALK TO BARRY'S SUCCESSOR ABOUT -- AND RORRIE AND SAY LET'S DO THE STUDY AGAIN WITH CURRENT -- I DON'T MEAN TO TRIVIALIZE THAT ANSWER BUT IT'S A BIT OF THE BIG MOVING TARGET WE FACE AND THERE'S NOT REALLY A GOOD ANSWER TO THAT. OTHER THAN TO SAY THE ONLY THING THAT WE DO KNOW IS THAT WITH THE ADVENT OF IMAGING, WE SEE MORE TUMORS, IF YOU LOOK AT BIOPSY REPORT OF PERSON WITH IMAGING THEY HAVE THE TRADITIONAL 12 COARSE BECAUSE SENSITIVITY IS NOT 95%. THEN THEY GET ANOTHER SIX TO 12 COARSE SAMPLING FROM THE PROSTATE SO JUST -- IT WILL DRIVE UP THE NUMBER OF TUMORS THAT YOU WILL DETECT. >> CLAIRE TYMPANI IS STARTING A LARGE MULTI-PARAMETRIC MRI STUDY COMING MORE OUT OF THE NCTN THAN DCP. BUT ALTHOUGH THAT HAS SLIGHTLY DIFFERENT GOALS THAN WHAT YOU ARE TALKING HERE, THERE IS A LOT OF INFORMATION THAT WE'LL USE NOT ONLY AS TRADITIONAL MRI BUT THESE MORE ADVANCE VERSIONS TO BE ABLE TO GET EXACT QUESTION SO MAY NOT BE THE DATA YOU WANT BUT THAT TRIAL IS UNDERWAY. >> I'M SORRY, I WAS THINKING AS YOU WERE TALKING ABOUT THIS, THAT THERE IS A APPROXIMATE OPPORTUNITY TO ADDRESS YOUR QUESTION. SO PATIENTS WITH LOW GRADE DISEASE WE KNOW FROM A RANDOMIZE TRIAL ADMINISTRATION OF FIVE ARI WILL REDUCE FINDING CANCER AND REDUCE LIKELY HOOD OF UPGRADED CANCER, SO YOU COULD MARRY WITH TARGETED TECHNIQUES TO BE ABLE TO ANSWER THAT QUESTION AND THAT SELECTED POPULATION. >> I WOULD LIKE TO BRING WITH THIS COMMENT OR QUESTION. YOU'RE A UROLOGIST? ONE SLADE YOU SAID PROSTATE CANCER MORTALITY IS THE OUTCOME. IN TERMS OF TAMOXIFEN PREVENTION TRIAL SHOW INCREASE RISK OF UTERINE CANCER, HAD THERE NOT BEEN SURVIVAL ADVANTAGE, AND THEY ALL DIED OF UTERINE CANCER, DIFFERENCE STORY. THERE IS HIGH RISK OF OSTEOPENIA, OSTEOPOROSIS IN PROSTATE CANCER PATIENTS AS THEY AGE, HAD MORE DEVELOPED HIP FRACTURES AN DIED -- (OFF MIC) >> I HAVE LESSONS LEARNED FROM THIS WE TRIED TO TEACH OUR FELLOWS. BUT WHEREVER WE DESIGN A TRIAL, WE HAVE TO BE COGNIZANT OF THE KNOWN AND POTENTIALLY UNKNOWN ADVERSE EFFECTS OF THE DRUGS USING. SO THAT'S WHY LONG TERM FOLLOW-UP IS EXTREMELY IMPORTANT. WHEN WE STARTED BREAST CANCER PREVENTION TRIAL I DON'T THINK WE HAD A FIRM IDEA THAT WE WOULD BE SEEING A SIGNAL IN ENDOMETRIAL CANCER AND WE USE EXTERNAL INFORMATION AND WHEN IT STARTED TO EMERGE SO IT'S VERY IMPORTANT TO LOOK AT THE NET BENEFIT OR HARM. SO POINT WELL TAKEN, LONG TERM FOLLOW-UP IS IMPORTANT. SOME OF THE EFFECTS ARE FRONT LOADED BUT A LOT OF EFFECTS OF THESE MEDICATIONS MAYBE BACK LOADED. YOU CAN'T BE FOOLED INTO MISJUDGING BALANCE OF BENEFITS AND HARMS. THAT'S WHY LONG TERM FOLLOW-UP IS SO IMPORTANT. >> LITTLE BIT OF EDITORIAL COMMENT, LESSON THAT I LEARNED AND WE TRY TO TEACH IS THAT WE CAN'T FALL PREY TO THE TYRANNY OF EXPERTISE. AND AGGRESSIVE CANCER PREVENTION TRIAL WAS AT RISK OF FALLING TYRANNY TO -- FALLING PREY TO THAT TYRANNY. THAT IS INTERMEDIATEIAL END POINT, THE GLEASON SCORE USED TO MAKE AIONAL OS OF -- ASSUMPTION OF WHAT INEVITABLY WAS GOING TO HAPPEN, DEATH RATE FROM PROSTATE CANER WAS INEVITABLY GOING TO BE INCREASED IN THE FINETRIDE TRIAL WE TRIED TO TEACH OUR FELLOWS IN THE CANCER PREVENTION PROGRAM WHAT IT TAKES TO VALIDATE AN INTERMEDIATE END POINT, NOT TO ACCEPT EXPERT OPINION ON WHAT INTERMEDIATE END POINT MUST MEAN AND NOT TO MAKE PUBLIC HEALTH DECISIONS IMPORTANTLY BASED ON NON-VALID INTERMEDIATE OUTCOMES. >> MAYBE SELF-SERVING BUT WE SAW EXAMPLES HOW LINKAGES CAN EXTEND FOLLOW-UP AND ENRICH THAT DATA. JOE SAID SOMETHING IN PASSING IN TERMS OF THESE STUDY RELATIVELY WIDE EPIIN TERMS OF ELIGIBILITY CRITERIA, ALL COMESSERS DESIGN BUT IN TERMS OF LARGE PREVENTION TRIALS AND THERAPEUTIC TRIALS, THE ABLE TO SUBSEQUENTLY GENOMICALLY CHARACTERIZE AND LOOK AT -- IN MY OPINION, PROVIDES OPPORTUNITY TO MOVE TOWARD MORE TARGETED LATER ON BUT NOT WITHOUT A LARGE STUDY RANDOMIZED UP FRONT TO BEGIN WITH. >> ONE LAST POINT. THIS WOULD NOT HAVE BEEN POSSIBLE HAD WE NOT HAD SOCIAL SECURITY NUMBERS. AS SOMEONE POINTED OUT DURING THE BREAK, THERE'S A NEW -- YES, MA'AM. I KNOW. WHERE I'M GOING WITH THIS. >> >> I HOPE SO. >> NEW NUMBER SELF-SERVING NOW FOR THE NEXT GENERATION IF WE HAD THAT AND BE ABLE TO LINK IT NOT JUST IN PREVENTION TRIALS, THERAPEUTIC TRIALS, IMAGINE REDUCTION IN COST. IMAGINE REDUCTION IN COST IN ADDITIONAL DATA THAT YOU GET FROM IT BUT YOU'RE THE PERSON. >> KEEPING IN MIND MEDICARE CARDS ARE CHANGING, SOCIAL SECURITY NUMBER WILL BE REMOVED ONLY TO MAKE PREPARATIONS FOR THIS TWO YEAR TRANSITION PERIOD WHERE THE MEDICARE NUMBER MAY OR MAY NOT BE PRESENT, SOCIAL SECURITY NUMBER MAY OR MAY NOT BE PRESENT ON THE CLAIMS YOU'RE TRYING TO LINK. I THINK THE OTHER THING JUST TO KEEP IN MIND IS THAT MEDICARE HAS BEEN LINKING CLAIMS DATA FOR IF PURPOSES OF CANCER RESEARCH AS FAR BACK AS 1991. IF YOU ARE INTERESTED IN SEEING ESPECIALLY OUTPATIENT AND CARRIERS CLAIMS RELATED TO THE PATIENTS THAT YOU'RE INTERESTED IN STUDYING WE COULD TALK MORE AFTER THE SESSION. >> WHO DO I TALK TO? THE >> THE OTHER THING IS CURRENTLY MOST TRIALS DON'T CHECK. SO IT'S NOT LINKABLE RIGHT NOW. >> THE FDA MADE GREAT STRIDES IN THEIR POST APPROVAL DATA COLLECTION FOR THE PURPOSES OF REGISTRIES. REGISTRIES STARTED TO LEVERAGE THE ACCESSIBILITY OF MEDICARE CLAIMS, BY CHECKING THIS INFORMATION, GREAT EXAMPLE WOULD BE THE AMERICAN COLLEGE OF CARDIOLOGY. THEY HAVE TRANSVASCULAR SOCIETY THAT HAS BEEN COLLECTING NUMBER ANDING YOU IT ADS PART OF THEIR THREE STEP LINKAGE PROCESS SO THERE'S OPPORTUNITIES THERE TO U SEE HOW THE INFORMATION COULD BE IMPROVED AND IN ABSENCE OF THAT INFORMATION CAN GET 60 TO 70% LINKAGE USING DATE OF BIRTH SO FIRST AND LAST NAME, ADDRESS, ALL THAT INFORMATION THAT YOU USE FOR LINKAGE TO NATIONAL DEATH INDEX. >> THIS IS GREAT. THANK YOU, GENTLEMEN, THIS WAS AN OUTSTANDING SESSION. THANKS FOR THE HERCULEAN EFFORT IN PUTTING TOGETHER THIS TRIAL. TERRIFIC. NEXT UP IS DR. SZABO, CHIEF OF LUNG AND UPPER AIR DIGESTIVE RESEARCH DIVISION WHO WILL TALK ABOUT THE PREVENTIVE PIPELINE. SO AS WE THINK ABOUT WHERE WE ARE NOW, WE'LL EAR GOING IN THE FUTURE. >> CAN EVERYBODY HEAR ME? THANK YOU FOR THIS OPPORTUNITY TO TALK TO US -- TO TALK TO YOU ABOUT DCP EARLY PHASE CLINICAL TRIALS PROGRAM AND THE DRUGS THAT ARE IN THE PIPELINE. WE ARE SWITCHING GEARS A LITTLE BIT HERE. WE KNOW DEVELOPMENT OF CANCER IS A LENGTHY PROCESS AND ACTUALLY THE OPPORTUNITIES FOR PREVENTION ARE QUITE LONG. THE EARLY PHASE CLINICAL TRIALS PROGRAM COVERS MAJORITY OF THAT LIFETIME OF THE CANCER. THE OBJECTIVES OF THE PROGRAM ARE TO QUALIFY PREVENTIVE AGENTS FOR FURTHER CLINICAL DEVELOPMENT, IT'S THE PHASE 0 THROUGH 2 CLINICAL TRIALS THAT ASSESS PRELIMINARY EFFICACY AND PROVIDE NEEDED RATIONALE TO GO TO PHASE 3 SUCH AS YOU JUST HEARD ABOUT. AS THIS IS A SCIENCE UNDER DEVELOPMENT STILL WE ALSO LOOK TO OPTIMIZE PEARL CLINICAL TRIAL DESIGNS, THESE TRIAL CAN BE QUITE DIFFICULT TO DEVELOP SURROGATE INTERMEDIATE END POINT BIOMARKERS, TEST NOVEL TECHNOLOGYINGS, IMAGING AND MOLECULAR TO DIAGNOSE PRE-EXISTING LESIONS AND DEVELOP INSIGHTS TO MECHANISMS OF CANCER PREVENTION BY STRATEGIES BEING STUDIED. SO THE TYPES OF STUDIES THAT WE PERFORM PHASE 0 MICRODOSING STUDIES THAT MODULATE BIOMARKERS, PHARMACOKINETIC SAFETY TRIALS AND PHASE 2 EFFICACY TRIALS, WHICH ARE THE BULK OF THIS PROGRAM, AND THESE ARE OFTEN PLACEBO CONTROLLED. THE PRE-MALIGNANCY INSULIN TRIAL IS MOST INFORMATIVE BUT REQUIRES SCREENING AND BIOPSY TO IDENTIFY THOSE INDIVIDUALS WHO HAVE PRE-MALIGNANT LEAGUES AT RISK TO DEVELOP CANCER IN A SHORTER TIME FRAME. ONE CAN ALSO LOOK AT MOLECULAR ENPOINTS AND WE TUSH TO CLINICAL TRIALS TO ASSESS INTERVENTION ON OVER CANCER AND OFTEN ON PRE-MALIGNANT LEAGUES AND SURROUNDING HISTOLOGICALLY BUT NOT MOLECULARLY NORMAL EPITHELIUM. OUR CURRENT PROGRAM IS A CONTRACT FUNDED PROGRAM, THE MAP SHOWS YOU THE STARS FIVE CONTRACTORS, WE HAVE MANY SITES OVER A HUNDRED, AND IN THE FIVE YEARS OF CURRENT PROGRAM WE APPROVED 43 TRIALS, MANY ARE ACTUALLY STILL ONGOING SINCE THEY WERE APPROVED OVER THAT PERIOD OF TIME. WE ARE RIGHT NOW IN THE MIDST OF OUR COMPETITION TO RENEW THIS PROGRAM, IT WILL NOW BE AS CANCER PREVENTION CLINICAL TRIALS NETWORK OR CPCT NET. IN FAIRLY MAJOR CHANGE MOVING TO A COOPERATIVE AGREEMENT. SO RIGHT NOW WE HAVE ON THE STREET TWO RFAs, ONE FOR THE SITES THAT WILL PERFORM, THE CLINICAL TRIALS, AND ONE FOR A COORDINATING CENTER, WHICH HELPS MAKE THIS INTO A FUNCTIONAL NETWORK THAT MOVES FORWARD. IN FACT, THERE ARE DEADLINE FOR RECEIPT OF APPLICATIONS IS NEXT WEEK. SO I CAN'T TELL YOU HOW THE PROGRAMS IS GOING TO MOVE FORWARD. BUT THE AREAS OF EMPHASIS ARE SOME OF THE SAME AREAS THAT YOU REALLY HEARD BARRY TALK ABOUT IN HIS TALK. WE ARE ALWAYS LOOKING FOR NEW SCIENTIFIC AREAS ROBUSTLY BEGUN TO INVEST IN IMMUNOPREVENTION AS A STRATEGY. WE ARE INTERESTED IN OPTIMIZING THE RISK BENEFIT FROM AGENTS AND GOING WITH AGENTS THAT WE KNOW THAT HAVE EFFICACY AND DEVELOPING AGENTS THAT ACTUALLY CAN BE USED SO REGIONAL DRUG DELIVERY, I'LL GIVE EXAMPLES OF THIS IN TERMS OF TOPICAL BREAST CANCER PREVENTION APPROACHES. ALTERNATING DOSING REGIMEN SUCH AS INTERMITTENT DOSING WHICH DECREASE TOXICITIES AND COMBINATIONS ARE ALL IMPORTANT ASPECTS OF OUR PROGRAM. WE HAVE ALSO PUT EMPHASIS ON USING DRUGS FOR MULTIPLE CHRONIC DISEASE AND REPURPOSING OLD DRUGS WHILE PREVENTIVE INTERVENTIONS, I WILL TALK ABOUT METAPHORMAN SPECIFICALLY. FROM YOU HEARD ABOUT ASPIRIN SUFFICIENTLY FROM DR. SHARPLESS AND FROM BARRY. WE ARE LOOKING FORWARD TO THE OTHER NCI ACTIVITIES SUCH AS THE MOON SHOT AND PRE-CANCER ATLAS AND IN IF PARTICULAR TO HELP GUIDE US INTO THE PROPER -- TO IDENTIFY THE PROPER TARGETS FOR INTERVENTIONS SO WE CAN REALLY PERSONALIZE PREVENTION IN THE FUTURE. SO JUST AS AN EXAMPLE, WE ARE AN INTEGRATED DIVISION. BARRY SHOWED THE THREE LEGGED STOOL WITH PREVENT PROGRAM. UAB 30 IS EXAMPLE OF A DRUG THAT'S COME FROM PREVENT PROGRAM WITH ROBUST DATA SHOWING IT EFFECTIVE IN ER POSITIVE AND NEGATIVE MOUSE MODELS. THIS IS A SPECIFIC REXNOID THAT DOESN'T HAVE THE HYPERGLYCERIDEMIA. IN OUR PRE-CLINICAL PROGRAM USED TO BE CALLED RAPID BUT NOW PREVENT, THE PHASE 1 STUDIES WERE PERFORMED IN OUR CLINICAL TRIALS PROGRAM AND WE ARE NOW IN PHASE 1B BREAST CANCER PRE-SURGICAL TRIAL LOOKING AT VERYRYING DOSES AND SHORT EXPOSURE WITH END POINT OF KI 67 IN BREAST CANCER ITSELF. WE HAVE NUMBER OF STUDIES, IN IMMUNOPREVENTION. AND THESE WILL FORM THE BASIS FOR FUTURE PHASE 2 TRIALS, BARRY ALLUDED TO THE IMMUNOVACCINE STUDY BUT LOOKING AT OTHER PROTECTIVES VACCINES, WHICH IS ALSO DEVELOPED BY THE PREVENT PROGRAM AND AS ALWAYS READY TO GO INTO PHASE 1 FISHES IN HUMAN TRIAL. WE LOOK AT HPV THERAPEUTICS WITH COMBINATION OF TOPICAL FIVE FU AND TLR 7 AGONIST. THIS IS JUST NOW ENTERED PHASE 1 AS A COMBINATION. THERE ARE SEVERAL TUMOR ASSOCIATED ANTIGEN STUDIES, # VACCINE, GLYCOSYLATED PROTEIN THAT IS EXPRESSED IN IN MANY ADENOCARCINOMAS AND ALSO IN MANY MALIGNANCIES. THESE ARE EARLY PHASE CLINICAL TRIALS. NORA DESIS VACCINE A MULTI-PEPTIDE VACCINE, THAT HAS WHOLE IGF RECEPTOR 1, PEPTIDES, TO -- IN A PHASE 1 STUDY, WITH IMMUNOGENICITY END POINTS, PSA VACCINE IS ALSO IN STUDIES. SO SO LET ME FOCUS A LITTLE BIT ABOUT BREAST CANCER OF PREVENTION AND TOPICAL APPROACHES, WHY WOULD THIS BE THE WAY TO GO. THE BREAST IS A REALLY A SKIN DERIVED STRUCTURE WITH A VERY WELL DEVELOPED INTERNAL LYMPHATIC CIRCULATION. AND DRUGS THAT ARE APPLIED TO THE BREAST REACH HIGHER CONCENTRATIONS, LOCALLY THAN WHEN APPLIED ELSEWHERE IN THE SKIN. AND WE ALREADY KNOW THAT TAMOXIFEN IS AN EFFECTIVE DRUG BUT NOT BEING USED SUFFICIENTLY SO THERE'S SEVERAL ONGOING STUDIES, FOR INSTANCE ONES WITH FOUR HYDROXY TAMOXIFEN WHICH IS A TAMOXIFEN METABOLITE, A PRIOR PHASE 2 STUDY THROUGH OUR PROGRAM SHOWED TOPICAL EXPOSURE, TOPICAL APPLICATION TO THE BREAST VERSUS ORAL TAMOXIFEN IN WOMEN UNDERGOING SURGERY FOR DCIS WITH ABOUT AN EIGHT WEEK EXPOSURE RESULTED IN SIMILAR DECREASE IN PROLIFERATION IN THE DCIS LESION AS WITH TOPICAL AS WITH SYSTEMIC. WITH FORMER CONCENTRATIONS BUT MUCH LESS SYSTEMIC EFFECT. SO NOW WE HAVE TWO STUDIES ONGOING TO MAKE -- THIS WAS A FAIRLY SMALL STUDY TO MAKE DATA MORE ROBUST, AND IMPORTANTLY THERE'S A PHASE 2B PLACEBO CONTROLLED TRIAL LOOKING AT WOMEN WITH MA'AM GRAPHICALLY DENSE BREASTS, 12 MONTH INTERVENTION WITH PRIMARY END POINT OF BREAST DENSITY. AND THIS IS AN FDA APPROVABLE END POINT. SO THIS IS I THINK OUR MOST LIKELY CANDIDATE IF THE STUDY IS POSITIVE, TO MOVE FORWARD INTO PHASE 3. OTHER AGENTS BEING STUDIED, ONE IS ANTI-PROGESTIN, THE LITTLE GRAPH ON THE RIGHT SHOWS DECREASE IN TUMOR INCIDENCE IN MICE TREATED WITH CARCINOGEN NMU. THIS STUDY WAS COMPLETED IN PRE-SURGICAL STUDY AND WE ARE LOOKING AT THE END POINT WHICH IS TISSUE CONCENTRATION THROUGHOUT THE BREAST NKICS 67. THERE ARE TWO ADDITIONAL AGENTS THAT ARE EARLIER IN THEIR DEVELOPMENT, ANOTHER TAMOXIFEN METABOLITE ENDOFONIN AND REXNOID WHICH IS POTENTIALLY EFFECTIVE IN ER NEGATIVE BREAST CANCER AS WELL. BOTH IN PHASE 1 RIGHT NOW. IN TERMS OF LOOKING AT DRUGS THAT COULD BE REPURPOSED FOR CHEMOPREVENTION THERE HAS BEEN A ROBUST LITERATURE DEVELOPING OVER THE LAST DECADE OR MORE. SUGGESTING THAT METAPHORMAN USE CAN DECREASE CANCER INCIDENCE. BUT THAT DATA IS -- ARE CHUTELY AFFECTED BY MULTIPLE CONFOUNDERS AND BIASES. WE TEAMED UP WITH COLLEAGUES AT THAT TIME EUROPEAN INSTITUTE OF ONCOLOGY IN MILAN, TO PERFORM META ANALYSIS THAT SPECIFICALLY CORRECTED FOR BMI, FOR INSTANCE, AND TIME RELATED BIASES. AND FOUND THE EFFECT OF METAPHORMAN WAS ACTUALLY MUCH LESS ROBUST FROM EPIDEMIOLOGICAL STUDIE, THAN WOULD HAVE BEEN PREVIOUSLY REPORTED IN THE LITERATURE. SO I THINK BARRY ALLUDED TO THIS, DIABETES PREVENTION PROGRAM OUTCOME STUDY, WILL PROVIDE VERY IMPORTANT INFORMATION ABOUT OVERALL CANCER INCIDENCE IN THE HIGH RISK POPULATION OF -- METABOLIC SYNDROME. BUT IT WON'T GIVE US A GOOD IDEA ABOUT SPECIFIC TARGET ORGANS, SO WE HAVE PERFORMED AT THIS POINT FOUR PHASE 2 TRIALS LOOKING AT THE ABILITY OF METAPHORMAN TO IMPACT BIOMARKERS AT THE TISSUE AT RISK IN BARE ROT'S ESOPHAGUS, IN PROSTATE CANCER AND VERY UNDERPOWERED STUDY AND IN COLORECTAL FOCI. AND NONE FOUND SIGNIFICANT EFFECT ON BIOMARKERS AT THE TISSUE AT RISK. WE MOST RECENTLY PERFORMED A PHASE 2A STUDY ORAL LEUKOPLAKIA, ORAL RISK FOR CANCER YOU NEVER FIND SIGNAL FOR THAT IN DPP. THE RESULTS THERE WERE NOT AS PROMISING AS WE WOULD LIKE. CLINICAL RESPONSE RATE WAS 18%, DOCUMENT PAIRED TO 20, 30% HISTORICAL CLINICAL RESPONSE RATE. THE HISTOLOGIC RESPONSE RATE WAS BETTER BUT THERE ARE BIASES THAT COME INTO PLAY THERE. THAT IS QUITE A WEEKEND POINT THUS FAR SO WE ARE PERFORMING MANY ADDITIONAL BIOMARKERS ANALYSIS INCLUDING SEQUENCING OF THESE LEAGUES TO GET BETTER UNDERSTANDING OF METAPHORMAN'S EFFECT IN THIS DISEASE BUT THUS FAR WE DO NOT HAVE ANY MORE DATA TO MOVE FORWARD TO PHASE 3 AND GOING FROM EPIDEMIOLOGICAL DATA IN PEOPLE WITH DIABETES TO A CLINICAL CANCER PREVENTION TRIAL NOT IN DIABETES IS A HUGE STRETCH WITH THE DATA THAT ARE AVAILABLE. SO I THINK THIS SLIDE HERE, IS FOR YOU TO ENJOY AT YOUR LEISURE. SHOULD YOU WANT TO LOOK AT THIS PRESENTATION BUT THERE ARE A NUMBER OF IMMUNOPREVENTIVE AGENTS AS WELL AS CHEMOPREVENTIVE AGENTS, THE RED ONES HAVE COME THROUGH OUR PREVENT PROGRAM, AND THAT WE ARE LOOKING TO MOVE FROM CLINICAL TO PHASE 1, OR EARLY PHASE 1 TO PHASE 2 TO LATER PHASE 2 AND MAYBE WITH FOUR HYDROXY TAMOXIFEN TO PHASE 3 AFTER ALL THE DATA ARE AVAILABLE. WITH THAT I WANT TO GO BACK TO THE THREE LEGGED STOOL. OUR PROGRAM SIT IN THE MIDDLE OF EARLY PHASE DEVELOPMENT THANK YOU TO PHASE 3 TOLL PROVIDE IMPORTANT DATA THAT SHEPHERD NOVEL STRATEGY AND SOME OLD STRATEGIES FORWARD. >> WE'LL HAVE YOU COME UP AND HAVE SOME QUESTIONS AFTERWARD SO WHILE YOU GUYS -- THE REST OF CTAC, ONE OF THE REASONS WE ARE DOING THIS PRESENTATION IS TO GET FEEDBACK ON THIS AREA OF EMPHASIS. SO ONE THING THAT HE WILL PRESENT ON PAGE 3 AREA OF EMPHASIS FOR THE PROGRAM, WHAT YOU MIGHT DO IS LOOK AT THAT AS WE THINK ABOUT QUESTIONS IN OUR PANEL DISCUSSION LATER ON. DR. HAWK IS VICE PRESIDENT DIVISION HEAD OF CANCER PREVENTION POPULATION SCIENCE AT MD ANDERSON AND JUST ONE OF THE MOST FAMOUS PEOPLE IN THE FIELD HERE. SO GREAT TO HAVE YOU HERE. THE NIH WANTS CANCER PREVENTION SCREENING COMMITTEE TO EVALUATE DIFFERENT CANCER PREVENTION TRIALS DEVELOP BY N CORE AND I WILL HAVE WERTA TO COME HERE TOO. HE'S CO-CHAIR OF THE STEERING COMMITTEE AND WILL GIVE YOU OVERVIEW OF OPPORTUNITIES AND CHALLENGESES REGARDING CANCER PREVENTION CLINICAL TRIALS. THANK YOU. >> THANK YOU VERY MUCH, PATRICK, IT'S A SMALL FIELD IF I'M A MAJOR FIGURE ANYTIME. BUT DELIGHT TO BE HERE WITH YOU TODAY. I'M A PRODUCT OF ONE OF OF THE PROGRAMS BARRY HIGHLIGHTED, CANCER PREVENTION FELLOWSHIP PROGRAM HERE AT NCI. AREA OF CANCER REPREENINGS IS IMPORTANT PART OF THE MISSION FOR MD ANDERSON 40 YEARS WE'RE CELEBRATING 40 ANNIVERSARY OF ENUCLEATION IN OUR MISSION STATEMENT. AND THE DIVISION I LEAD IS IN PLACE 25 YEARS. SO THAT'S A NOTABL YEAR FOR US AS AN ORGANIZATION FOR THE FIELD OF PREVENTION ON YOU ARE CAMPUS. WHAT I HOPE TO DO HERE OVER THE NEXT FEW MINUTES IS HIGHLIGHT WHERE THE FIELD STANDS FIRST AND FOREMOST AND SHARE SOME OF THE EXCITING OPPORTUNITIES AND CHALLENGES THAT THIS BODY, THAT I CO-CHAIR WITH GARY GOODMAN HAS RECENTLY CONVENED AROUND. TO POINT OUT WAYS WE FEEL GREAT PROGRESS COULD BE MADE T. IN TALKING PREVENTION WE HAVE TO GO WHAT IS THE BOTTOM LINE? THIS SLIDE ATTEMPTS TO CAPTURE THE OPPORTUNITY PREVENTION REPRESENTS FOR OUR POPULATION. THAT IS BEST ESTIMATES CURRENTLY, RANDOMIZE CONTROL TRIALS, ALSO IMPORTANTLY HIGH QUALITY LONG TERM PROSPECTIVE STUDIES, SUGGEST UP TO A THIRD HALF OF CANCER IN WESTERN POPULATION U.S. R&D PREVENTABLE BUT THAT IS DIFFICULT TO ACHEEF IT REQUIRES INTERVENTION AND BEHAVIOR THAT SPAN THE LIFE SPAN AND ED'S OPERATIONALIZED AT A PERSONAL LEVEL AS WELL AS POPULATION LEVEL IN BOTH OF THOSE COMPLIMENT ONE ANOTHER SO ON THE PERSONAL SIDE FIRST YOU CAN SEE EIGHT DOMAINS OF ACTIVITY THAT ARE CURRENTLY RECOMMENDED BASED UPON BEST AVAILABLE EVIDENCE. MAINTAINING A HEALTHY WEIGHT ACROSS THE LIFE SPAN, EATING A HEALTHY DIET BEING PHYSICALLY ACTIVE, AVOIDING TOBACCO AND LIMITING TYPICALLY IN AND INDICATION IT'S CANCER RISK REDUCTION RATHER THAN USE OF WORD PREVENTION OR TREATMENT OF PRE-CANCEROUS LEEINGS BUT 14 AGENTS -- LEAGUES BUT 14 AGENT VERSUS GONE THROUGH THE FDA PROCESS FOR PREVENTION RISK REDUCTION OF TREATMENT OF PRE-CANCEROUS LESIONS. SEVERAL FOR TOPICAL AGENTS JUST AS EVA ALLUDED TO, THE ABILITY TO TREAT PRE-CANCEROUS LESIONS WITH FEWER SYSTEMIC SIDE EFFECTS SO INDEED THE FIELD HAS RECOGNIZED A LOT OF PROGRESS OVER ITS RELATIVELY BRIEF SPAN. I NOW WANT TO MOVE FROM CURRENT STATE OF THE FIELD INTO A DISCUSSION OF SUGGESTIONS COMING FROM CANCER PREVENTION STEERING COMMITTEE, WHOM I'M REPRESENTING HERE TODAY, YOU CAN SEE SOME 22 MEMBERS HERE. THAT ARE PROVIDED THEIR THOUGHTS ABILITY PROMISING DIRECTIONS FOR THE FUTURE. LET ME TURN TO THOSE NOW. FIRST IN T FIELD OF BIOLOGY AND BIOMARKERS THE GREATEST SUGGESTION OF THIS BODY WAS TO BETTER UNDERSTAND THE EARLY DETERMINANTS AND DRIVERS OF THE EARLIEST STAGES OF CANCER DEVELOPMENT THAT COMES FROM DATA AND IN KIND OF TWO DOMAINS, FIRST THE PROGRESSIVE CHARACTERIZATIONS OF SOMETHING LIKE COLORECTAL CANCER HERE THAT'S NOW BEEN SUBCATEGORIZED ON MOLECULAR BASIS TO FOUR SUBTYPES, CONSENSUS MOLECULAR SUBTYPES, THE FACT THERE ARE FOUR DIFFERENT MOLECULAR FORMS OF COLORECTAL CANCER, THAT'S BARING ON EFFECTIVE TREATMENT AT THIS POINT, LEADS TO THE QUESTION OF WHAT'S BEEN THE UPSTREAM DRIVERS OF THAT? IS THAT SAME BIOLOGY, HETEROGENEITY BIOLOGY REFLECTED IN PRE-CANCEROUS LESIONS FOR EXAMPLE. A VERY IMPORTANT QUESTION, TOO FEW ANSWERS AT THE MOMENT. SECOND WE THINK OF THE THE MODEL OF ADVANCE STAGE CANCER, HOW DOES THAT EVOLVE OVER TIME, DOES INTERRUPTION OF APOPTOSIS A KEY FEATURE IN SOMETHING THAT PROGRESSES VERSUS SOMETHING TA REMAINS STABLE, WE DON'T KNOW THE ANSWER TO THOSE QUESTIONS. SO THIS WHOLE IDEA OF PRE-CANCER ATLAS IS STRONGLY ENDORSED BY OUR COMMITTEE, AND EXTREMELY GRATEFUL TO THE NCI BY RECOGNIZING AND FUNDING THROUGH THE CANCER MOON SHOT. STILL EVEN WITH THE FUNDED INITIATIVES WE THINK THERE'S MUCH MORE OPPORTUNITY TO BRING MORE BASIC BIOLOGY TO QUESTIONS OF EARLY CANCER DEVELOPMENT IN SOMETHING WE STRONGLY ADVOCATE. SECOND IN TERMS OF COHORT, THOSE AT RISK FOR CANCER, MOVING FROM THE GENERAL POPULATION TO HAVE BEEN INVOLVED IN STUDIES WE ED H ABOUT EARLIER, MEN WITH PROSTATE AND A CERTAIN AGE AND THEREFORE AT RISK FOR PROSTATE CANCER DEVELOPMENT REQUIRES A LARGE STUDY WITH LONG FOLLOW-UP, HOWEVER, AS ALLUDED TO EARLIER WE MAYBE ABLE TO IDENTIFY THOSE AT GREATER RISK WHO MAYBE WILLING TO MORE FREQUENTLY PARTICIPATE IN RESEARCH AS WELL AS BENEFIT FROM THAT RESEARCH AND ALSO MAYBE MORE TOLERANT OF ANY SIDE EFFECTS THAT ARE FOUND ALONG THE WAY. SO IDENTIFYING THOSE THAT INCREASE RISK IS VERY IMPORTANT OPPORTUNITY FOR THE FUTURE IN OUR OPINION. THAT COMES FROM FUNDAMENTALLY THREE THINGS, THAT ARE CHARACTERIZED DIFFERENT LEVELS. SO FIRST THOSE WITH DRAMATIC OR CUMULATIVE LIFETIME EXPOSURE TO CANCER CAUSING MEDIATORS YOU MIGHT SAY. AND THE COMMON ONES ARIST WILLED THERE. -- ARE LISTED THERE. SECONDLY, FAMILY HISTORY, WHICH I'LL SAY MORE ABOUT IN A MOMENT IS CHARACTERIZED AT GERM LINE LEVEL BUT HERE WE MIGHT THINK OF TRYING THE BETTER IDENTIFY FROM THE GENERAL PUBLIC THESE KINDS OF INDIVIDUALS WITH DRAMATIC EXPOSURE OR WITH FAMILY HISTORIES BY COLLECTING DATA MORE SYSTEMATICALLY REGARDING SOCIAL DETERMINANTS OF HEALTH AS WELL AS SOCIOECONOMIC FACTORS WHICH ARE VERY STRONGLY CORRELATED WITH CANCER OUTCOMES CERTAINLY HAVE TO DO WITH ACCESS BUT NOT EXCLUSIVELY TO ACCESS. SECONDLY, STANDARDIZING IMPROVING THE COLLECTION OF BEHAVIORAL AND FAMILY HISTORY DATA, PARTICULARLY AS IT EVOLVES ACROSS THE COURSE OF CLINICAL CARE, TYPICALLY IN PRIMARY CARE SETTINGS WE KNOW WE DO THAT EXCEPTIONALLY POORLY NOW. AND TENDS TO BE SPOTTY, EVEN IN OUR BEST INTEGRATED SYSTEM. NEXT GERM LINE MUTATION CHARACTER, YOU MIGHT SAY FAMILIAL PRE-DISPOSITIONS BUT NOW CHARACTERIZE IN A MORE SPECIFIC MANNER, HOW CAN WE MORE SYSTEMATICALLY SCREEN FOR THOSE TENDENCIES T A POPULATION LEVEL, LOTS OF DISCUSSION IN THE FIELD. LED BY MARY CLAIRE KING AN OTHERS WHETHER THIS SHOULD BE A MORE SYSTEMATIC PART OF CARE DELIVERY T. WHEN WE GET TO THAT POINT WE WILL BE DEALING WITH A MUCH GREATER INSIGHT IN TERMS OF INDIVIDUAL CANCER RISK AND THE OPPORTUNITIES TO INTERVENE IN WAYS THAT MIGHT BENEFIT THEM. THEN FINALLY, WE HAVE ALREADY HEARD ABOUT IDENTIFYING INDIVIDUALS WITH PRE-CANCEROUS LESIONS WHICH ESSENTIALLY INTEGRATE THE GENETIC TENDENCIES AS WELL CUMULATIVE LIFETIME EXPOSURE. THERE WE FELT NEED FOR SCIENCE TO DETECT SILENT LEAGUES. WE KNOW THAT IS -- LESIONS. THAT IS A DOUBLE EDGE SWORD YOU CAN'T OVERSCREEN OVERDIALING NOSE AN OVERTREAT BUT PROGRESSIVELY OVER TIME WE FIGURE THAT OUT AND PROBABLY THE BEST EXAMPLE IS SURGICAL CANCER WHICH IN WHICH 18 SHOULD BE A PREVENTABLE DISEASE THROUGH EFFECTIVE SCREENING WHICH CASE WE HAVE GONE THROUGH DIAGNOSIS OVERTREATMENT BUT PROGRESSIVELY GET BETTER ACROSS TIME. AS WELL AS REFINING THE CURRENT SCREENING SURVEILLANCE PROGRAMS TO BE ATTENTIVE TO THAT ISSUE OF RISK BENEFIT BALANCE. FINALLY, REALLY IMPORTANT AS WE HEARD EARLIER, TRYING TO DETERMINE WHICH OF THOSE PRE-CANCEROUS LEAGUES ARE TRULY CONCERNING AND LIFE THREATENING AND ASSOCIATED WITH SIGNIFICANT MORBIDITY, VERSUS THOSE THAT NAY REMAIN STABLE AND SOME CASE REGRESS ON THEIR OWN. THIRD PTOMAINE, I COVERED -- DOMAIN, I COVERED BIOLOGY AND BIOMARKERS, COHORTS, AGENTS, THE OPPORTUNITIES AS WE SEE THEM ARE TO TRY TO AVOID FALSE LEADS. THIS HAS BEEN THE HOPE RATHER THAN REALITY, WE SEE HERE THAT EARLY ON FOR EXAMPLE THE CASE WE'RE HIGHLIGHTING HERE IS SELENIUM VITAMIN E TRIAL IN PROSTATE CANCER BUT THERE WERE OTHERS WE COULD HAVE HIGHLIGHTED JUST POINTING OUT THAT OBSERVATIONALLY AS COMING OUT OF LARGE RANDOMIZED CONTROL TRIALS, IS A SUGGESTION IT MAYBE USEFUL IN PROSTATE CANCER SUGGESTED VITAMIN E MAYBE SIMILARLY HELPFUL AND YET WHEN SUBJECTED TO LARGE LONG DEDICATED TRIALS STUDYING THIS QUESTION INDEED SHOWED THE INVERSE IN TERMS OF THIS IS HIGHLIGHTING IN PARTICULAR THE VITAMIN E RESULT THERE WHICH NOT STATISTICALLY SIGNIFICANT 0.06 BUT NEVERTHELESS A BIT CONCERNING, OF COURSE EXTENDED FOLLOW-UP JUST AS WE LEARNED IN THE FIRST PROSTATE TRIAL WOULD TELL THE TRUTH STORY OR AT LEAST BETTER PART OF THE TRUE STORY. SECOND, REALLY IMPORTANT OPPORTUNITY IS TO RECOGNIZE THAT NCI BARES THE BRUNT OF THIS FIELD. IN OTHER AREAS THERAPEUTICS ARE IMAGING WE OFTEN HAVE PRIVATE PARTIES THAT ARE SUPPORT THIS WORK BUT IN PREVENTION REALLY STILL IT'S NCI AND NCI ALONE THAT CARRIES THE WATER FOR FUNDING THIS ENTIRE FIELD. THIRD POINT POINT IS THE OPPORTUNITY TO LOOK AT REPURPOSES ESTABLISH THERAPEUTICS AGENTS FOR PREVENTION RISK REDUCTION OR CANCERS WHATEVER THE INDICATION WOULD BE, THE POSTER CHILD FOR THAT OPPORTUNITY IS TAMOXIFEN WHERE EARLY DATA OBSERVATIONAL IN NATURE SUGGESTED THAT PREVENTED BENEFIT SUBSEQUENTLY PROVEN IN RANDOMIZE CONTROLLED LARGE TRIAL. THIS TO OUR MIND ALONG WITH SOME OTHER OBSERVATIONS, YOU MIGHT GO BACK TO ONE OF THE OLDEST AGENTS DEVELOPED IN ANIMAL MODELS LOOKING AT ADENOMA OUTCOMES AS WELL AS INTENTIONAL CANCER OUTCOMES IN ANIMAL MODELS. AND THEREFORE HAD PREVENTED POTENTIAL NEVER BEEN TESTED FOR PREVENTIVE POTENTIAL BUT IT'S NOW A MARKETED THERAPEUTIC IN TREATING PRE-CANCEROUS LESIONS THROUGH THE SKIN THROUGH THAT TOPICAL APPROACH, NOT THE SAME IN A CHEMOTHERAPEUTIC COMPLEX AND VASTLY ALTERED REGIMEN SHOWN PREVENTATIVE OR TREAT PRE-CANCEROUS LEAGUES TAMOXIFEN THE BEST EXAMPLE IN THE FIELD. ANOTHER IMPORTANT OPPORTUNITY FOR FUTURE AGENT COMBINATION, THEY WORK IN IMPORTANT IN IMPORTANT SHUTS DISEASE AND CANCER TREATMENT, WE FEEL THE SAME FOR THE FIELD OF CANCER PREVENTION, VERY FEW HUMAN STUDIES YET TESTING THAT CONCEPT HIGHLIGHTING THE MOST RECENT, THERE WAS ALSO A LARGE STUDY LOOKING AT INFLAMMATORY ANTIBODY THAT INHIBITS POLYAMINES WHICH ARE NOT THE USUAL 30% REDUCTION IN RISK BUT IN THAT CASE MAYBE EVEN 90% REDUCTION IN RECURRENT ADENOMAS, THIS IS RECENT DATA OUT OF PATIENTS WITH FAP SHOWING THE COMBINATION OF TWO AGENTS THAT WORK IN ISOLATION IN THIS PATIENT POPULATION, DECREASE THE UP PER INTESTINAL BURDEN OF PRE-CANCEROUS LEAGUES AS WELL AS IN THIS CASE -- LESIONS AS WELL AS THE COLONIC BURDEN OF THOSE PRE-CANCEROUS LESIONS WITH 69% REDUCTION BEFOREDUCTION AFTER SIX MONTHS OF THERAPY SUGGESTING COMBINATIONS ARE IMPORTANT FOR PREVENTION, PARTICULARLY PROBABLY IN HIGH RISK INDIVIDUALS GOING FORWARD. NEXT AREA, IMPORTANCE WE HAVE HEARD DEIMPLEMENTATION SCIENCE, TAKE SOMETHING WHERE WE HAVE EFFECTIVE STRATEGIES, SUCH AS CERVICAL CANCER SCREENING AND PROGRESSIVELY LEARN THE FIRST IMPACT OF THAT USUALLY IS REDUCTION IN MORTALITY, DEMONSTRATED NEAR TERM FOLLOWED THEN BY OVERSCREENING OVERDIAGNOSIS OVERTREATMENT MANY TIMES BUT THEN ULTIMATELY DEVELOPING BETTER TESTS AND LEARNING HOW TO APPLY THOSE TESTS BETTER, SO THAT YOU CAN REALIZE MORE OF THE BENEFIT AND LESS RISK BUT LOTS OF OPPORTUNITY, HIGHLIGHTS CERVIX AND PROSTATE WHERE THERE'S A LOT OF WORK AS WE HEARD IN THE PRESENTATION. FINALLY, IN TERMS OF OPPORTUNITIES FOR N CORE NETWORK ITSELF,, OUR MEMBERS HIGHLIGHTED THE NEED FOR MORE INTERACTION COORDINATION OF EFFORTS ACROSS GROUPS SO NOW WE ARE USING OUR MONTHLY SCHEDULED STUDIES NOT JUST REVIEW PROMISING CONCEPTS BUT RATHER TALK ABOUT THE FIELD AND HOW WE CAN PROMOTE IT TOGETHER. IMPROVING THEM PLATE FOR SUBMISSIONS. WE HAVE MANY SUBMISSIONS MANY FAILED TO WIN SUCCESS LARGELY BECAUSE OF ISSUE WE FEEL WE COULD HAVE ADDRESSED MORE PRODUCTIVELY UP FRONT FROM IDENTIFYING WHAT THE THRESHOLDS MIGHT BE. CREATE DISSEMINATING THRESHOLD STANDARD FOR PRELIMINARY DATA THAT RELATES TO THE IDEA OF TEMPLATING THE SUBMISSION, FOURTH COLLABORATING MORE PRODUCTIVELY IN PARTICULAR WITH SUBSPECIALISTS WHO MANY TIMES HAVE ACCESS TO HIGH RISK COHORTS AND INTERVENTIONS REQUIRED TO ASSESS BENEFIT. SO WORKING PARTICULARLY WITH GASTROENTEROLOGIST PULMONOLOGIST DETERMINE DERMATOLOGIST, ET CETERA WHO NOT ONLY SEE HIGH RISK PATIENTS BUT DO BIOPSIES FOR PROPER CHARACTERIZATIONS. AND FINALLY LOOKING ACROSS THE GROUP TO TRY TO IDENTIFY HIGH RISK SUBSETS SUCH AS THOSE THAT ARE GERM LINE CARRIERS OF MUTATION THAT PLACE AT INCREASE RISK. FANLY I WANT TO END ON BROADER CONCEPT, MOVING AWAY FROM CLINICAL TRIALS PER SE, THIS DEPICTS THE 0 THROUGH T-4 RESEARCH ENTERPRISE WHICH WE IDENTIFY FIRST EXCITING DISCOVERY AND TAKE IT TO THE PROCESS OF CLINICAL TRIALS AND ULTIMATELY INTO DISSEMINATION IMPLEMENTATION AND POPULATION LEVEL. DOWNSTREAM WE CREATE LARGE BODY OF EVIDENCE IN THE DOMAIN THAT I WOULD CHARACTERIZE AS CANCER CONTROL ISSUES OF POLICY EDUCATION, COMMUNITY BASED DELIVERY TO ACHIEVE A CULTURAL TRANSFORMATION AND TRY TO LIVE UP TO THE IDEA OF DISCOVERING ARE, DEVELOPING AND DELIVERING A WHOLE PROGRAM, THAT HIGHLIGHTS QUALITY IN DELIVERY AN REACH EVERYONE. THE BIGGEST CHALLENGE IS THAT OPPORTUNITY THERE DEPICTED HERE IN THE CENTER OF THE SLIDE, RESPONSIBLE PARTIES INVOLVED IN THAT DELIVERY ARE NUMEROUS AND COMPLEX. THIS TO MY MIND, IS MIND, OF THE AREAS WE WOULD USE A GREAT DEAL MORE LEADERSHIP BY THE NCI CANCER CENTERS IN PARTICULAR IN TRYING TO DRIVE ENTERPRISE OUT TO SEE EFFICACY AND EFFECTIVENESS AT POPULATION LEVEL, I THINK AGAIN THE NCI AN NCI DESIGNATED CANCER CENTERS, CAN BE BIG PART SERVING AS ADVOCATES, INSTITUTES AND DRIVES OF THIS CHANGE. BIGGEST CHALLENGE IS ALL OF THEM ARE UNDER FUNDED TO BE INVOLVED IN THIS DOMAIN THIS HELPS POPULATION LEVEL, SOCIETAL LEVEL BUT INDIVIDUAL RESPONSIBILITY AND CONTRIBUTION OF ANY ONE OF THESE ENTITIES REQUIRE LEADERSHIP TO BRING THEM TOGETHER TO SEE THAT LEVEL OF EFFECTIVENESS. WITH THAT THANK YOU FOR YOUR ATTENTION AND BRING MY PRESENTATION TO CLOSE, HAPPY TO TAKE QUESTIONS IN JOINT SESSION. FROM >> THANK YOU FOR AN OUTSTANDING TALK. IF I CAN HAVE -- DO YOU WANT TO STAND? THEY TALK ABOUT THIS THREE LEGGED STOOL, SEEMS LIKE IT WILL FALL OVER WITHOUT YOU HAVE YOUR PRESENCE AT THE END OF THE TABLE THERE. THE BIG QUESTION HERE, WE HAVE A FEW MINUTES BUT WHAT WE LIKE TO DO IS TO HAVE THIS COMMITTEE PROVIDE SOME INSIGHT IN TERMS OF AREAS OF INTEREST TO DEFINE PRIORITIES. YOU MIGHT HAVE TALKED ABOUT PREVIOUSLY AN MAY SAY A FEW WORDS BUT ONE OF THE THINGS THAT STRIKES ME IS THE HUGE IMPORTANCE OF PREVENTION WORK BUT ALSO I'M JUST BOGGLED BY TRIALS THAT HAVE 35,000 PEOPLE ON THEM AND YET THERE'S VERY LITTLE DIFFERENCE WHATSOEVER. I THINK THAT IT DIMINISHES THE ENTHUSIASM SO TO HELP YOU GUYS OUT WOULD BE HELPFUL FOR US TO DEVELOP PERHAPS PRIORITIES AND PERHAPS STRATEGIES HOW WE CAN DO THESE TRIALS WITH LESS PATIENTS BUT DO YOU HAVE ANY COMMENTS? >> WHAT'S THE ISSUE U? WE NEED TO DO BETTER, IT'S 2018, NOT 1998 OR 1993. THE QUESTION IS IT SEEMS, IT AMAZES ME THE BUDGET GOES UP AND THEN LINE GOES DOWN, BECAUSE WE -- THINGS ARE JUST NOT AS FACILE IN TERMS OF WHERE FUNDS ARE TO DO THESE VARIOUS THINGS. SO I THINK THAT IT WOULD BE USEFUL TO ME, I HOPE I'LL START WITH ERNIE, IF YOU HAVE ONLY ONE OR TWO PRIORITY AND ED'S 2018, WHERE -- IT'S 2018, WHERE SHOULD WE INVEST? THOUGH WE HAVE A BIG BUDGET WHERE SHOULD WE INVEST? >> GOOD QUESTION, ONE I STRUGGLE WITH AT ANDERSON AS WELL. I THINK PART OF IT PROBABLY IS PREDICTING THE FUTURE. EHR SEEM TO BE HERE TO STAY AND FIGURING HOW TO USE IT THE IDENTIFY RISK GROUPS WHICH WILL REQUIRE HUMAN ACTIVITY AS WELL. IT WILL REQUIRE FRONT LINE CLINICIANS, WE HAVE A HARD TIME GETTING OUR ONCOLOGISTS TO DO A COMPLETE HISTORY AND PHYSICAL MUCH LESS A FAMILY HISTORY ON ENTERING INTO THE INSTITUTION. TRYING TO AUTOMATE THE PROCESS AND WHETHER THAT ACHIEVES THE BENEFIT OR NOT IS THE RESEARCH QUESTION. THAT'S A VERY IMPORTANT PART. JUST AS WE HEARD IN THE PRIOR EXAMPLE, SYSTEMATIC LONG TERM FOLLOW-UP IS WHAT WE'RE MOST INTERESTED IN, WE WANT TO KNOW PROSTATE CANCER SPECIFIC MORTALITY BUT THE BIGGER ISSUE IS WHAT'S THE IMPACT OVERALL MORTALITY FUNCTIONING MORBIDITY, ET CETERA. SO IN THE EHR ARE WHERE THE SORTS OF DATA SHOULD LIVE IN THE FUTURE. SO TRYING TO FIGURE OUT HOW TO INTEGRATE EHR INTO THE DELIVERY OF CANCER AND IN MORE BROADLY, IN PREVENTION, SYSTEMMATIC ASSESSMENT OF INDIVIDUAL RISK IS ONE OF THE BIG PLACES THAT I WOULD PUT IT AS A STARTING PLACE, I HAVE TO THINK ABOUT IT, MAYBE MY COLLEAGUES HAVE OTHER GREAT IDEAS. >> THIS THAT IS A CURVE BALL. I THINK THAT ONE OF THE THINGS WE STRUGGLE WITH IDENTIFYING WHICH AGENTS TO USE IS WE DON'T UNDERSTAND THIS VAST PART OF THE BIOLOGY OF WHAT HAPPENS, THERE ARE MANY CANCERS, THERE ARE MANY WAYS IN GIVEN TART ORGAN SUCH AS LUNG TO DEVELOP CANCER SO NOT ONLY DO WE NOT KNOW WHO THE HIGHEST RISK COHORTS ARE, BUT GIVEN HETEROGENEITY HOW BEST TO ADDRESS IT SO I THINK WE NEED TO MAKE A MAJOR INVESTMENT IN UNDERSTANDING THE BIOLOGY OF EARLY CANCER. >> I'LL MAKE A COMMENT IN WHAT'S OUTSTANDING FOR THE COMMITTEE SETTING IS THIS IS A SIGNIFICANT SOURCE FOR THE PATIENTS WHO CERTAINLY ARE AT RISK AND ONE OF THE CHALLENGES IS INCORPORATING THOSE DISCIPLINES AND PRACTITIONERS WHO HAVE THE PATIENTS AND HOW THEY FIT INTO THE ORGANIZE OF PROVIDING THEM. THERE IS ROOM ABOUT THE FUND I CAN SHOE BECAUSE DISCIPLINES -- ISSUES -- THEY PROVIDE SERVICES BUT THEY ARE NOT ACTUALLY ON THE PART OF THE FUNDING INFRASTRUCTURE. SO I THINK THAT'S ONE OF THE AREAS WE CAN ADDRESS. >> THAT DIDN'T ANSWER YOUR QUESTION? >> OF COURSE NOT. WE GOT TO HAVE A CONVERSATION. RESOURCES ARE LIMITED. AND THESE ACTIVITIES ESPECIALLY POPULATION ACTIVITIES, CAN BE -- DON'T HAVE TO BE BUT CAN BE EXPENSIVE. SO I THINK IT'S A GREAT THING FOR THIS COMMITTEE WHICH IS NEVER IN THE PAST REALLY SPENT TIME TRYING TO GIVE INPUT IN THIS AREA, TO FROM TIME TO TIME, THIS IS ONE OF THOSE TIMES TRYING TO PICK YOUR BRAIN BECAUSE ANYBODY WHO THINKS THEY DON'T NEED HELP IN THIS AREA IS PROBABLY DILUTED THEMSELVES AND THE ISSUE I WOULD BRING BACK TO YOU ABOUT THE EHR, I DO HAVE A WIFE WHO STAYS UP UNTIL TWO IN THE MORNING TRYING TO FILL OUT HER MEDICAL RECORDS AND GIVES ME NO END OF GRIEF THAT I DON'T HAVE TO DO THAT ANY MORE. >> SO I WANT TO PUSH BACK ON THAT, THINK YOU DID HEAR THREE VERY STRONG ANSWERS TO THE QUESTION WHAT ARE THE NEEDS IN THE FIELD. FIGURING HOW TO INTEGRATE DATA AND GET PRACTITIONERS TO ENTER DATA IS REALLY IMPORTANT PRESSING NEED PARTICULARLY ACROSS TIME. SO THAT'S -- THAT CAN BE AN ACTION TAKEN OR A QUESTION TO BE ASKED. I THINK PROBABLY THE BEST WAY TO ASK THE QUESTION HOW TO DO AND SEE TO IT IT'S DONE SOMEHOW. SECOND, IDENTIFICATION OF HIGH RISK INDIVIDUALS SIN CREDIBLY IMPORTANT, IT IS THE KEY TO BIG PART OF THE FUTURE OF PREVENTION. AND THIRD, THE IDEA OF UNDERSTANDING BIOLOGY WAS HIGHLIGHTED BY OUR COMMITTEE, HIGHLIGHTED IN EVERYTHING THAT YOU HEARD IN MY PRESENTATION, I THINK AS WELL AS EVAS SO THE PRE-CANCER GENOME ATLAS IS A GREAT STEP AND IMPORTANT DIRECTION BUT MUTT PUTTING MORE MONEY SO WE CAN ATTRACT MORE SCIENTISTS TO IT WAS THE POINT OF ONE OF THE PAPERS I PRESENTED THERE IS INCREDIBLE OPPORTUNITY THERE, THOSE ARE THREE AREAS KEY INVESTMENTS CAN BE MADE AND REALIZE A PROFOUND BENEFIT TO THE POPULATION. >> DEB. >> I AGREE WITH THE BIOLOGY PIECE AND PARTICULARLY IF YOU'RE THINKING ABOUT HOW TO DO SMALLER TRIALS, HAVING VALIDATED SURROGATE BIOMARKERS OF SUCCESS IS CRITICAL, BECAUSE THERE'S NO WAY TO GET AROUND THAT. I ALSO WANT TO BRING UP TWO THINGS, THOUGH IT'S A HYPOTHESIS , BEHAVIORAL CHARACTERISTICS THAT YOU PUT ON THE SCREEN, THE POTENTIAL RISK REDUCTION WAS GREAT OR GREATER THAN FINASTRIDE SO WE DON'T KNOW ENOUGH ABOUT THOSE SORTS OF THINGS AND WE NEED TO UNDERSTAND IT BETTER. SO WE CAN ACTUALLY DO THOSE TRIALS THAT CAN PROVE WHAT IT CAN DO AND THEN FIGURING WAYS TO DEVELOP THE ABILITY TO HAVE PEOPLE DO IT BECAUSE THE PRIMARY CARE SYSTEM IS OVERWHELMED, AND WE HAVE GOT TO FIGURE OUT WAYS TO ACTUALLY HELP THE HEALTH OF OUR POPULATION. THE LAST THING I WANT TO SAY IS JUST WENT OUT MY BRAIN. FROM SHOOT. ILL HAVE TO COME BACK, IT WAS A REALLY GOOD POINT. >> LIKE THAT TED CRUZ MOMENT. I JUST LIKE -- >> I'M SORRY. >> I LIKE TO RESPOND TO THAT A MINUTE. WE HAVE HAD A GREAT DEMONSTRATION OF THE IMPACT OF FOCUSING ON BEHAVIOR AND THAT BEING TOBACCO OVER LAST 50 YEARS, SEEING RATES POPULATION LEVEL FALL FROM 50% DOWN TO NOW, 15 TO 20% THROUGH BOTH CONCERTED ACTIONS IN BOTTOM SLIDE TOWARD POPULATION THROUGH POLICY PUBLIC EDUCATION, PROVIDER EDUCATION, DELIVERY OF COMMUNITY BASED SERVICES AND CESSATION COMBINED WITH CLINICAL ACTIVITIES OF CESSATION HAVE REALLY BEEN WHAT'S RESULTED IN A TREMENDOUS FALL. WE CAN'T TAKE CREDIT FOR LUNG CANCER OTHER TOBACCO ASSOCIATED CANCERS THROUGH EFFECTIVE THERAPY IN MOST INSTANCES AND THAT'S COME FROM EMPHASIS IN POPULATION LEVEL PREVENTION. Q. I REMEMBER. (OFF MIC) >> BECAUSE FOR EXAMPLE, WHEN I ASK THE QUESTION ABOUT WHO WAS THERE CLEAR BENEFIT IN THE PCPT FOR ONE GROUP VERSUS ANOTHER, I WAS TOLD MOLECULARLY BIOLOGICALLY CLINICALLY, NOTHING, BUT WHAT ABOUT SOCIAL DETERMINANTS OF HEALTH. PERHAPS THAT IS A MISSING PIECE THAT HAS POWER WE ARE NOT COLLECTING AND WE NEED TO DEVELOP THE INFRASTRUCTURE TO BE ABLE TO GET ALL THAT INFORMATION INTO THE PUZZLE. >> I WAS GOING TO SAY SOMETHING DIFFERENT, ONE OF THE THINGS YOU LEARN, I TRY TO MAKE A POINT EARLIER ONE THING YOU LEARNED FROM THOSE STUDIES WERE MAJOR RESOURCE INPUT. NOW THEY'RE STILL TRYING TO FIGURE OUT, TALK TO DR. THOMPSON, ONE THING WEAR TRYING TO FIGURE OUT RIGHT NOW IS ARE THERE GENETIC DETERMINANTS THAT HELP DECIDE WHERE YOU'RE GOING TO GO. THE ANSWER THERE IS IT'S STILL YET UNKNOWN. I THINK AT SOME POINT AND I DON'T KNOW WHEN THAT POINT WILL BE, WE HAVE SEEN EXAMPLES WHERE YOU CAN LEARN FROM THESE STUDIES AND I HOPE WE'REING TO MAKE RESOURCE INPUT WHEN WE CAN BECAUSE TO SAY WE ALWAYS ARE GOING TO DO SMALL STUDIES, I THINK IS A WRONG STRATEGIC MOVE, I THINK WE NEED TO -- I JUST DON'T KNOW WHEN THAT IS BUT WE GOT TO BE WILLING TO MAKE THAT DOLLAR ADJUSTMENT WHEREVER THOSE DOLLARS COME FROM. >> IF I COULD JUST RESPOND TO THAT, IS THAT WE TOTALLY AGREE THAT THE REASON TO DO SMALL STUDIES IS NOT TO CONTINUE TO DO SMALL STUDIES BUT TO REALLY GET A ROBUST AMOUNT OF EVIDENCE TO GIVE US A HIGHER CHANCE OF DOING A LARGER HOPEFULLY NOT AS LARGE AS IN THE PAST STUDY THAT CAN GIVE US A POSITIVE ANSWER, SO WE FULLY AGREE WITH YOU. >> I WANT PATIENTS TO FOLLOW IN THESE STUDIES. >> I WANT TO COMMENT ABOUT THE BIOLOGY, WE CAN'T EMPHASIZE THAT ENOUGH OF UNDERSTANDING THE MECHANISTIC BECAUSE I THINK WE HAVE GONE AROUND AND AROUND ON SURROGATE OR INTERMEDIATE END POINTS AND DECIDING WHEN VICTORY IS DECLARED ON A PREVENTION. IT'S UNSATISFYING SO I THINK THERE NEED TO BE MORE METHODOLOGICAL THOUGHT PUT INTO THAT. AND MAKING SOME FIRMER RULES OR WHATEVER ABOUT WHAT WE'RE GOING TO REALLY DECLARE WE HAVE SUCCESSFULLY PREVENTED, THAT WOULD LEAD TO THE MORE EFFICIENT TRIALS. THAT'S REALLY THE POINT, THE OTHER ELEPHANT IN THE ROOM I WANTED TO MAKE WAS IN WITH RESPECT TO THE FAP TRIAL, BECAUSE THAT'S AN OVERWHELMINGLY PENETRANT GENE HAVING AN APC MUTATION. SO WHAT'S THE ELEPHANT IN THE ROOM IS THERE IS ACTUALLY WDESPREAD PROPHYLACTIC SURGERY, THAT'S NOT LISTED IN ANYONE'S COMMENTS TODAY ABOUT A STRATEGY AND PROPHYLACTIC MASTECTOMYTO PROVE PROPHYLACTIC PAN TRIATECTOMY. GIVE SOME THOUGHT TO THAT. IT'S ACTUALLY HAPPENING. AND YOU HAVE NOT BROUGHT IN THE SURGICAL COMMUNITY ON THIS. >> >> ABSOLUTELY THERE ARE GUIDELINES IN SPECIFIC COHORTS, WITH SPECIFIC DISEASE FAP BEING ONE, PROPHYLACTIC SURGERY IS EFFECTIVE. BUT COMES WITH LOTS OF IT OWN ISSUES INCLUDING NOT BEING ABLE TO GET EVERYTHING THE ENTIRE FIELD SO IT'S ONE OF THE MANY PARTS OF ARMAMENTARIUM, IT'S NOT SOMETHING THAT WE ARE STUDYING SPECIFICALLY, I DIDN'T RAISE IT IN OUR PROGRAM. BUT WE'RE NOT AVERSE TO DOING STUDY -- >> GOAL IS WHETHER CHEMOPREVENTION IS DELAYING SURGERY OR INEVITABLE POTENTIALLY. >> THAT WOULD BE ONE GOAL. IS TO DELAY FOR INSTANCE BEYOND CHILD BARING YEARS, SO ON. YES. >> ONE OF THE THINGS THAT COMES TO MINE IS THE SCIENCE IN HERE IS SO GOOD. THINKING ABOUT IAN'S TRIAL MASTERFUL BUT IN TODAY'S DOLLARS HOW MUCH THAT COSTS TO DO BIOPSIES AND COST OF THESE TRIALS ARE SO ENORMOUS THAT WE SPEND SO MUCH TIME ON WHO BUT WOULD BE GREAT IF THERE WAS SUB-- HOW CAN WE CONDUCT TRIALS IN A CHEAPER WAY, WHAT MECHANISMS CAN WE DO INSTEAD OF DATA MANAGERS CAN WE USE APPS TO FOLLOW-UP ON -- SOMETHING BUT A STRATEGIC APPROACH TO CUT IT DOWN. THIS MAY FIT INTO A CONVERSATION I WAS HAVING EARLIER ABOUT TRIALS IN GLOBAL HEALTH. WHEN YOU DO TRIALS IN LOW TO MIDDLE INCOME COUNTRIES YOU HAVE TO FIGURE OUT A WAY TO DO A TRIAL MUCH MORE CHEAPLY THAN YOU DO IN THIS COUNTRY. THERE COULD BE LESSONS LEARNED HOW TO TRANSPORT HERE, WE HAVE TO FIGURE OUT WAY TO DO IT IN ORDER TO GET TRIALS THAT HAVE ENOUGH POWER TO MAKE A DIFFERENCE, RANDOM THING. DAVID. FROM >> SEEMS TO ME ONE OF THE CHALLENGES YOU HAVE COMPARE TO THERAPEUTIC TRIALS WE'RE USED TO IS NO INTERMEDIATE END POINTS READILY AVAILABLE. WE CAN MEASURE RESPONSE OR HAVE SOME INDICATING AND IDENTIFY FUTILITY EARLY ON. I'M WONDERING SINCE YOU ARE COLLECTING SCREENING MATERIALS FROM THESE FOLKS ANYWAY. STANDARD SCREENING WHICH IS BLOOD, TISSUE IMAGING, WHETHER COLLECTING THOSE DATA AND MINING THEM NOT ONLY FOR BETTER DETECTION TECHNIQUES IT WOULD BE HELPFUL, AS IMAGER FOR EXAMPLE IF YOU CHECK MAMMOGRAMS WE'RE REALIZING NOT ONLY IS THERE'S SOPHISTICATION WE CAN ADD FROM COMPUTER ANALYSIS STANDPOINT THAT MAY HAVE RELATIVE IF WE CAN CHECK THE DATA RELATIVELY INEXPENSIVE APPROACHES TO DATA MINING AND LOOKING NOT ONLY FOR BETTER DETECTION BUT BIOMARKERS I'M WONDERING TO WHAT EXTENT YOU INTEGRATED THAT SCREENING DATA COLLECTION WITH YOUR PREVENTION STRATEGY. >> EVERYBODY COMPLAINS HOW EXPENSIVE STUDIES ARE, PART IS BECAUSE OF EXACTLY -- WE MAYBE LOOKING AT ORAL LEUKOPLAKIA WHICH DOESN'T HAVE AN IMAGING COMPONENT THOUGH IT COULD. BUT WE WILL COLLECT BLOOD, WE CAN OFTEN COLLECT MANY OTHER NORMAL TISSUE AND SO ON. THAT IS THERE TO BE MINED AND TO BE MINED BY THE COMMUNITY. NOT JUST BY THE INVESTIGATORS. >> I WASN'T REALLY THINKING IMAGING PER SE BUT THE WAY TO LEVERAGE SCREENING BEST TECHNIQUE THERE AND CERTAINLY WE HAVE GOTTEN MECHANISMS IN PLACE WHERE IT'S RELATIVELY INEXPENSIVE IF YOU DO IT IN A TARGETED FAKINGS TO COLLECT IMAGES AND THERE'S JUST A WEALTH OF CAPABILITY GOING BACK AND TRYING TO FIND SOMETHING THERE. EARLY INDICATION THAT THESE COMPUTER ANALYSIS TECHNIQUES ARE GOOD AT PREDICTING RISK AND MAYBE PREDICTING BENEFIT AN RISK REDUCTION. >> >> THESE ARE QUESTIONS FOR DR. SZABO. IN VIEW OF THE TREMENDOUS SUCCESS OF CHECK POINT INHIBITORS IN LUNG CANCER, IMMUNOPREVENTION I DIDN'T SEE NOT EVEN MENTION OF CHECK POINT INHIBITORS. WE DON'T KNOW THE IMMUNOLOGY OF THE DISPLASTIC LESIONS. BUT THE HIGH RATE DOESN'T OCCUR OVER OVER NIGHT. WE DON'T KNOW WHETHER IT'S -- THAT NEEDS TO BE SOMETHING EXPLORED AND BROADLY WE WOULD FIND THIS DISAPPEAR WITH CHECK POINT INHIBITOR THAT -- IS THAT SOMETHING THAT IS INCLUDED? >> WE HAVE NOT SPECIFICALLY MOVED INTO THE CHECK POINT SPACE. THERE'S CERTAINLY SOME AREAS WHERE YOU -- ONE WITH THEIR EYES POTENTIALLY MORE EFFECTIVE, FOR INSTANCE MISMATCH REPAIR COHORT, MULTIPLE CANCER. THERE ARE I THINK TWO STUDIES THAT ARE BEING DONE IN THE COMMUNITY, THAT ARE ACTUALLY LOOKING AT CHECK POINT INHIBITORS, SMALL MAXIMUM NUMBER OF DOSES WITH BRONCHIAL DISMAY SHAH FOR ONE AND NOT -- DYSPLASIA, NOT SURE IF MD ANDERSON IS OR OTHER NODULES. OTHERS MOVED TO THE SPACE, WE HAVE NOT YET. >> THERE IS AN OPPORTUNITY FOR EFFICIENCY. THINK IT WOULDN'T BE DEFINITIVE BUT AROUND THE IDEA OF CHECKING OTHER DATA IN THERAPEUTIC TRIALS, FOR EXAMPLE IN LYNCH SYNDROME WHERE AGENTS ARE BEING DEVELOPED, GATHERING THE DATA ON COLONOSCOPIES AN FOLLOW-UP SURVEILLANCE IN A SYSTEM MA IT CAN WAY AND POINTING OUT WHETHER THE PREVALENCE OR INCIDENCE OF RECURRENT ADENOMAS ARE HIGHER, LOWER, UNCHANGED WOULD BE ONE WAY TO TRY TO MOVE IN EFFICIENT SUPPLEMENTAL STRATEGY UNDER THE THERAPEUTIC TRIALS ONGOING AND MIGHT PROVIDE EARLY INDICATION. THAT'S HOW THEY WOULD BE BUT NEVERTHELESS VERY IMPORTANT WAY TO ADVANCE FIELD OF PREVENTION AD THERAPEUTIC AGENTS IN A THERAPEUTIC CONTEXT. >> TWO QUICK TOPIC. ON THIS TOPIC OF OPERATIONAL EFFICIENCY THIS OBVIOUSLY HAS BEEN SOMETHING THAT INDUSTRY HAS PUT INVESTMENT IN, MOSTLY MORE THAN TO MY KNOWLEDGE DONE BY CONTRACTORS OUTSIDE VENDORS SO YOU MENTION THE PHONE APP WHEN JACKIFY WAS APPROVED BY PHONE APP IT WAS BY VENDOR NOT THE INSIGHT COMPANY. BUT THE VENDORS HAVE DONE RESEARCH HOW TO SUCCEED AT THIS AND WHERE CERTAIN POPULATIONS LIKE ELDERLY DON'T COMPLY WELL, THOSE SORTS OF THINGS, ARE AVAILABLE REGARDING ATTRACTING SCIENTISTS, THIS IS A QUESTION, ARE THESE TRIALS ALSO DOWNLOADED AND SOMETHING AVAILABLE TO OUTSIDE SCIENTISTS LIKE PROJECT DATA SPHERE WHERE IF THEY'RE IN SAS DATA SETS OUTSIDE SCIENTISTS, I HAVE BEEN IMPRESSED WITH PROJECT DATA SPHERE WITH BOTH CONTROL ARM AN TREATED ARM, THERE IS LEARNING THAT CAN BE GAINED BY HAVING THAT AVAILABLE AND IT DOESN'T NEED TO BE SOMETHING WHERE YOU HAVE TO PAY FOR SOMEBODY'S TUITION OR FELLOWSHIP OR SOMETHING TO BE PART OF YOUR GROUP. THEY CAN JUST ACCESS IT ONLINE. COULD YOU COMMENT? >> SO THE CLINICAL TRIALS THAT I HAVE BEEN INVOLVED WITH WHICH IS THE EARLY PHASE TRIALS ARE SMALL FOR THE MOST PART, THEY HAVE NOT BEEN UP LOADED INTO ANY KIND OF DATABASE THAT IS AVAILABLE. FROM WE ARE DEVELOPING A BIOREPOSITORY FROM THE LAST FIVE YEARS AND MOVING FORWARD WHICH WILL HAVE CLINICAL TRIALS DATA AS WELL, THOSE WILL BE MADE AVAILABLE TO THE COMMUNITY BUT THROUGH NCI INTERFACE. THE AMOUNT OF DATA THAT YOU GET FROM A PCPT COMPARED TO WHAT WE DO IS MANY LOSS DIFFERENT SO THE AMOUNT OF INFORMATION TO BE MINED IS MUCH LESS IN THOSE EARLY PHASE STUDIES. BUT WE DEFINITELY ARE WORKING ON MAKING INFORMATION AVAILABLE OUTSIDE THE INVESTIGATOR IN THE PROGRAM. >> AS I UNDERSTAND THE VALUE OF -- YOU CAN TAKE MULTIPLE SMALL TRIALS AND DO META ANALYSIS TO ADDRESS THING LIKE FOR INSTANCE I HAVE BEEN LOOKING AT REGIONAL DIFFERENCES IN SAFETY ISSUES, AND FINDING THEM BUT WERE NEVER DISCUSSED OR PUBLISHED BY THE PRIMARY INVESTIGATORS. OR LOOKING EVEN ADHERENCE AND COMPLIANCE RETENTION ON STUDY, MISSING DATA IS THERE SOMETHING ABOUT DEMOGRAPHIC THAT COULD BE A BETTER AREA OF FOCUS AGAIN, THOSE ARE THE KIND OF THINGS HAVING A LARGER DATA SET THAT PEOPLE CAN ADDRESS, BECOMES AN ADVANTAGE. >> THANK YOU FOR THAT SUGGESTION. >> ANY OTHER QUESTIONS? I'M GOING TO MOVE -- MAIN THING NAME YOUR REASON WE'RE HERE TODAY IS LEGISLATIVE UPDATE. THAT'S THE ONLY REASON I'M HERE. SO I WANT TO GIVE THEM ENOUGH TIME TO BE ABLE TO PRESENT BUT WE HAVE LUNCH -- WE'LL MEET AT A QUARTER TO 1:00. OUTSIDE HERE SO WE'LL MOVE THE AFTERNOON SESSION UP A LITTLE BIT QUICKER HERE. SO THANK YOU FOR ALL THIS. WE BREAK NOW FOR LUNCH. >> GIVING US AN OVERVIEW, I'LL TRY TO FOCUS ON THE NUMBER OF PATIENTS THAT HAVE BEEN ON PREVENTION TRIALS AND IT DOVETAILS WITH PRESENTATIONS BEFORE LUNCH IN TERMS OF OTHER PREVENTION TRIALS. IT'S ALL YOURS. >> GOOD AFTERNOON. THANK YOU. I'M PRESENTING ON ACCRUAL ANALYSIS IN THE NCORP PROGRAM SINCE INCEPTION IN 2014, AND TALK ABOUT THE ACCRUAL WITHIN THE BROAD RESEARCH AREAS THAT WE DO HAVE. AND ALSO TALK ABOUT WHO PARTICIPATES IN THE NCORP TRIALS AND FINALLY TALK ABOUT OUR EFFORTS TO DEVELOP GUIDANCE FOR EFFICIENCY IN CONCEPT AND PROTOCOL DEVELOPMENT. WE HAVE CANCER CONTROL, PREVENTION, BUT THEY DIDN'T SAY WE HAVE BROADENED DEFINITION OF PREVENTION THAT INCLUDES SCREENING, POST TREATMENT SURVEILLANCE AS WELL, OUR CANCER CONTROL IS PRETTY MUCH ENCOMPASSED BY SYMPTOM MANAGEMENT AND TREATMENT, AND CANCER-RELATED TOXICITIES. WE ALSO ENROLL QUALITY OF LIFE PATIENTS INTO -- THAT ARE EMBEDDED IN TREATMENT TRIALS, AND WE HAVE BROUGHT INTO OUR RESEARCH PORTFOLIO CANCER CARE DELIVERY RESEARCH LED BY DR. ANN GIGER AND HER TEAM, AND ADVANCE IMAGING AND TREATMENT TRIALS FROM DCTD. IT'S IMPORTANT TO UNDERSTAND OUR RESEARCH BASES ARE THE ORGANIZATIONS THAT DEVELOP CONCEPTS AND PROTOCOLS FOR OUR COMMUNITY SETTINGS AND OTHERS AS WELL. THERE ARE SEVEN RESEARCH BASES, FUNDED TO MANAGE STATISTICS AND DATA MANAGEMENT FOR TRIALS. FIVE OF THEM ARE ALSO NCTN GROUPS BUT THEY ARE FUNDED SEPARATELY TO CONDUCT TRIALS FOR CANCER CONTROL PREVENTION AND OUR RESEARCH PORTFOLIOS. THERE ARE TWO RESEARCH BASES IN OUR ACADEMIC CENTERS, THEY ARE PARTICIPATING IN DEVELOPING CANCER CONTROL TRIALS. SO THE RESEARCH BASES ARE EXPECTED TO CHOOSE FROM PREVENTION, SURVEILLANCE OR CANCER CONTROL, THEY DON'T HAVE TO DO ALL OF THEM. THEY ARE REQUIRED ALL TO DO CANCER CARE DELIVERY RESEARCH, AND TO INTEGRATE CANCER DISPARITIES WHERE APPROPRIATE. SO, MOST OF THE CONCEPTS AND PROTOCOLS AND IDEAS COME THROUGH THE RESEARCH BASES, THEY ARE FUNDED TO THAT AND COME FROM THEIR OWN INTRINSIC EXPERTISE. THE NCORP HAS BECOME A LABORATORY FOR OTHER INVESTIGATORS WHO WISH TO HAVE DIVERSE PRACTICES, EXTEND RESEARCH PRACTICES, FUND RESPECTIVE INSTITUTIONS SO THERE'S SEVERAL MECHANISMS, THEY BE OBTAIN FEDERAL FUNDING FROM RPG POOL. ALSO WE HAVE INVESTIGATORS WHO COME IN FOR NON-FEDERAL FUNDING WITH THEIR RESEARCH PROJECTS SUCH AS PCORI AND ACS AND ALL OF THOSE. BUT ALL OF THEM ARE FUNNELED THROUGH THE RESEARCH BASES. IT IS THERE THE MINORITY UNDERSERVED SITES HAVE OPPORTUNITY FOR INPUT FOR FEASIBILITY AND TO PARTICIPATE NUNSING BARRIERS IN ANYTHING THAT MIGHT HAMPER ACTIVATION AND SUCCESSFUL ENROLLMENT OF PATIENTS BUT ALSO PROVIDES AN OPPORTUNITY FOR THEM TO PARTICIPATE IN THE RESEARCH COMMITTEES AND ALSO BECOME LEADERS WITHIN THOSE RESEARCH COMMITTEES AS WELL. YOU'VE SEEN THE SLIDE. WE'RE GROWING EVERY YEAR BY INVESTIGATORS AND ADDITIONAL SITES AND CAN SHARE WITH YOU THIS IS PARALLEL BY A VERY DYNAMIC HEALTH CARE ENVIRONMENT THAT ACTUALLY IMPOSES CHALLENGES THAT WE ADDRESS VERY FREQUENTLY WITHIN OUR PROGRAM, PRESENTING TO US DIFFERENT LEADERSHIPS, HEALTH SYSTEMS OVERSEEING OUR COMMUNITY SITES, WE HAVE 12 MINORITY AND UNDERSERVED SITES. SO, THE AVERAGE NUMBER OF TRIALS ARE AVAILABLE TO OUR NETWORK PER YEAR IS 45, I'VE LISTED THE ONES HERE. WHEN WE STARTED NCORP SEVERAL LEGACY STUDIES WERE IN OUR PROGRAM AS WELL. THIS IS THE SLIDE THAT SHOWS ENROLLMENT FOR THE PAST -- SINCE NCORP HAS BEEN FUNCTIONING, RED IS TREATMENT, BLUE IS CANCER CONTROL. WE ASK INVESTIGATORS TO BALANCE THAT. IT SHOULD BE EVEN. IT DEPENDS UPON AVAILABILITY OF TRIALS. THE TREATMENT ENROLLMENT I THINK HAS NARROWED THE DIRECTION IN WHICH TREATMENT TRIALS HAVE BEEN GOING, WITH SMALLER TRIALS, LESS OF THE VERY LARG ADJUVANT TRIALS, AND WE ALSO HAVE HAD A DIFFERENT I THINK CADRE OF OUR CANCER CONTROL AND SYMPTOM MANAGEMENT STUDIES WHICH ARE BECOMING MORE MECHANISTICALLY DRIVEN AND MORE COMPLEX TO OUR INVESTIGATORS AS WELL. THE SORT OF UPTICK IN 2017 IN CANCER CONTROL REFLECTS ENROLLMENT INTO THE TRIAL. I'M SHOWING THE SAME ENROLLMENT OF THE OVER 24,000 PATIENTS BY THE COMMITTEES AND MINORITY UNDERSERVED SITES. SO, WE ADDED IN 2014 CANCER CARE DELIVERY RESEARCH STUDIES, THIS WAS A VERY IMPORTANT ADDITION. THIS IS A MULTI-DISCIPLINARY SCIENCE THAT LOOKS AT CLINICAL OUTCOMES AND PATIENT WELL BEING AND ALLOWS FOR INTERVENTIONS TO REDEFINE OUR ACCRUAL WHICH IS ONE OF THE THINGS I WANT TO STRESS TODAY. SO WE'RE NOT ONLY LOOKING AT OUTCOMES FOR PATIENTS BUT WE INCLUDE CLINICIANS AND ORGANIZATION FACTORS THAT INFLUENCE CARE DELIVERY. WHAT I HAVE LISTED BELOW ARE OTHER ACCRUALS, NOT JUST PATIENTS, THEY COULD BE CAREGIVERS, THEY COULD BE CLINICIANS, PHYSICIANS, PHARMACISTS, AND I'LL SHARE A LITTLE BIT MORE ABOUT THAT WITH YOU. SO, IF WE LOOK AT WHAT OUR INVESTIGATORS DO, I'VE SHOWN THE ENROLLMENT FOR CANCER CONTROL PREVENTION, AND TREATMENT. WE ALSO DO QUALITY OF LIFE. WE HAVE NOT RECOGNIZED THE ACCRUAL -- IT HASN'T COUNTED AS A METRIC FOR INVESTIGATORS BECAUSE IT WAS PERCEIVED AS BEING PERHAPS DOUBLE DIPPING ALTHOUGH IT ISN'T BUT QUALITY OF LIFE WHICH IS BECOMING INCREASINGLY IMPORTANT AS WE UNDERSTAND THE NON-INTERVENTIONS, MEDICAL INTERVENTIONS WITH OUR PATIENTS, SO ON THIS SLIDE WE'RE INCLUDING QUALITY OF LIFE ACCRUALS AS WELL AS CANCER CARE DELIVERY ACCRUALS, 26% INCREASE IN ACCRUAL FOR THE NETWORK. WE ALSO PROVIDE OUR SCIENCE THAT'S DEVELOPED WITHIN THE NCCOR SITES, OTHERS ROSTERED IN THE NCT AND PROGRAMS SO THEY ENROLL INTO OUR QUALITY OF LIFE STUDIES WHERE WE HAVE EXPERTISE, REVIEW AND GIVE FUNDING AND THEY PARTICIPATE IN CANCER CONTROL PREVENTION STUDIES THROUGH THEIR AFFILIATIONS WITH THE NCTN GROUPS. SO INCREASINGLY WE ARE LOOKING AT HOW -- WAYS TO GENERATE PRE-CLINICAL MODELS FOR CANCER, THIS REQUIRES QUITE A BIT OF WORK AS OUR INVESTIGATIVE SITES. I'M GIVING TWO EXAMPLES. ONE IS THE PATIENT DERIVED MODEL. ANY HAPPENED TO BE A PATIENT DERIVED XENOGRAPH MODEL, 2014, OUR INVESTIGATOR SITES WERE ORIGINALLY ASKED TO DO BLOOD SPECIMENS AND THEN TO DEVELOPING AND DOING PAIRS WITH TISSUE SPECIMENS AS WELL. SO THERE WAS ANOTHER RENDITION OF THIS. I THINK A COUPLE YEARS LATER. BUT IN TOTAL THERE ARE 194 SPECIMENS, MOST PAIRED SPECIMENS. ANOTHER TISSUE PROCUREMENT STUDY IS THE EARLY ONSET MALIGNANCY ONE, AN INITIATIVE TO LOOK AT DISPARITIES AMONG SIX CANCERS, THIS IS BEING CONDUCTED IN THE MINORITY UNDERSERVED FUNDED GROUPS. AND AFTER SOME CONTRACT NEGOTIATIONS, THE ACCRUAL BEGAN AND WE HAVE OVER 80 ENROLLMENTS INTO THIS INITIATIVE. SO, IF WE TALK MORE ABOUT PRECISION, IT'S BEEN DISCUSSED AT VARIOUS BOARDS THE NCORP WAS A CONTRIBUTOR TO THE MATCH TRIAL, 20% OF MINORITY ENROLLMENT FROM NCORP. FOR ADJUVANT AND LUNG MAP TRIAL AS WELL, ENROLLMENT FROM NCORP RANGED FROM 20 TO 40%, A DEMONSTRATION THERE WERE NOT BARRIERS, THE QUALITY OF SPECIMENS WERE OF THE SAME QUALITY AS ACADEMIC ONES. SO JUST TO SUMMARIZE AS WE LOOK AT ACCRUAL INCLUDING QUALITY OF LIFE, CANCER CARE DELIVERY RESEARCH AND TISSUE ACQUISITION, THAT'S IMPORTANT BECAUSE SPECIMENS OBTAINED ARE INCREASINGLY VIGOROUSLY COLLECTED, CLINICAL ANNOTATION, WE WANTED TO GIVE SCIENTIFIC RECOGNITION TO SITES, MOVING FORWARD WE'LL DO THAT. ACCRUAL WILL COUNT FOR QUALITY OF LIFE AS WELL AS WE WILL GIVE A SCIENTIFIC ACCRUAL RECOGNITION FOR THE TISSUE ACQUISITION STUDIES AS WELL. NOW, THIS SHOWS THE SCREENING THAT WAS ACTUALLY DONE FOR THE PRECISION TRIALS FROM NCTN, BUT ALSO INCLUDES NUMBERS FROM OUR TRIALS THAT WE'RE NOT DOING GENETIC CHARACTERIZATION BUT WE ALSO HAVE TRIALS AS YOU HEARD THIS MORNING WHERE WE'RE LOOKING AT INDIVIDUALS WHO ARE INCREASED RISK OF DEVELOPING CANCER SO THE EFFORT TO ENROLL THOSE PATIENTS IS OFTEN CHALLENGING AND ENGAGING OTHER DISCIPLINES SO WE LOOKED AT OUR PORTFOLIO. THIS IS A COMBINATION OF PRECISION TRIALS WHERE THERE WAS SCREENING AS WELL AS SCREENING IN SOME OF OUR TRIALS. SO WE MAY NOT BE ABLE TO GIVE EXACTLY PER CASE SUPPORT BUT CERTAINLY FROM AN INFRASTRUCTURE PERSPECTIVE WE TOOK THIS IN CONSIDERATION WHEN WE ASKED FOR FUNDING AS WE MOVE FORWARD FOR OUR SECOND CYCLE FOR NCORP. SO I'D LIKE TO NOW MOVE INTO THE MINORITY ENROLLMENT WITHIN THE NETWORK, OVERALL MINORITY ENROLLMENT IS 24%, IT'S INCREASED OVER TIME. AS I RECALL WHEN WE HAD OUR EXTERNAL REVIEW ONE OF THE COMMENTS WAS TO INCREASE THE ENROLLMENT IN NON-MINORITY AND UNDERSERVED SITES, IT'S ABOUT 2% INCREASE FROM OVER THE PAST YEARS PER YEAR. IF WE LOOK AT THE MINORITY ENROLLMENT FROM THE COMMUNITY SITES, 18%, IT TOO HAS INCREASED, MINORITY UNDERSERVED SITES BY DEFINITION HAVING 30% IN THEIR CATCHMENT AREA OF RACIAL AND ETHNIC MINORITIES, MINORITY ENROLLMENT IS 54%. THESE ARE DATA THAT ARE GIVEN TO THE NIH FROM THE RESEARCH BASE PER PROTOCOL. SO, THERE'S A DIFFERENT BREAKDOWN FROM THE OBN, YOU ALSO HAVE ETHNIC DIFFERENCES AS WELL. THERE ISN'T THAT DIFFERENCE -- MUCH DIFFERENCE FROM DATA WE REPORTED IN THE PREVIOUS SLIDES BUT THIS GOES TO NIH AND IT'S I THINK VERY TEMPLATED IN TERMS OF HOW THE DATA ARE COLLECTED AND ALSO THERE'S DIFFERENCE FROM THE WAY THE PATIENTS REPORT IN CHARACTERIZE IN PUERTO RICO. SO, WE HAVE FREQUENTLY ASKED WHO PARTICIPATES IN OUR TRIALS. ARE THEY ALL HIGHLY EDUCATED? YOU KNOW, WHAT'S THE ECONOMIC STATUS? WHAT ARE THEIR INCOME STATUS AS WELL AS COMORBIDITIES? SO IN 2016 DIANE SAINT GERMANE AND I WORKED TO GET A SCREENING TOOL TO BETTER UNDERSTAND THE PARTICIPANTS IN OUR TRIALS. SO, WHAT WE SHOW HERE IS THAT WE'VE HAD 10,000 ENTRIES. WE WERE LOOKING AT DEMOGRAPHICS. WE LOOKED AT INCOME. WE LOOK AT EDUCATION, COMORBIDITIES, INSURANCE, METHOD OF DIAGNOSIS, AND OTHER BARRIERS TO PARTICIPATION. SO FROM THE NETWORK THERE WERE 10,000 ENTRIES, OVER 8,000 OF THEM CONSENTED, ONE MUST CONSENT TO GET THIS EXPANDED AMOUNT OF DATA. AND OF THOSE 8,000 WHO CONSENTED TO PROVIDE THIS ADDITIONAL DATA, OVER 6,000 OF THEM ENROLLED IN CLINICAL TRIALS. NOW, WE DO KNOW THAT ABOUT 11% OF THOSE WHO ENROLLED IN CLINICAL TRIALS WERE ALSO ON OTHER EXISTING TRIALS. NOW, THESE MAY HAVE BEEN TREATMENT TRIALS, THESE MAY HAVE BEEN THOSE INDIVIDUALS WHO WERE ENROLLING ON OUR SYMPTOM SCIENCE TRIALS FOR EXAMPLE SO YOU SEE THE NUMBER OF PATIENTS WHO SAID YES IN TREATMENT AND WHO SAID YES IN CANCER CONTROL IN BLUE, AND THOSE WHO DECLINED. IF WE LOOK AT THOSE 2500 PATIENTS WHO DECLINED AND WE ASK WHY THEY DIDN'T PARTICIPATE, IT'S ABOUT HALF THOSE WHO DIDN'T MEET THE ELIGIBILITY CRITERIA FOR THOSE ACTUALLY ELIGIBLE BUT DID NOT OPT TO PARTICIPATE IN CLINICAL TRIALS. WE USE THIS INFORMATION, FORMATIVE FOR US INTERNALLY AND ALSO RESEARCH BASES GET THIS INFORMATION BY PROTOCOL SO IT CAN HELP THEM LOOK AT BARRIERS. OF COURSE THE DATA THAT WE HAVE GOES DEEPER IN TERMS OF OTHER COMORBIDITIES. WE'RE ANALYZING THE DATA HOPEFULLY TO PREPARE FOR PUBLICATIONS OF THIS. WE LOOKED AT PATIENT INCOME. THIS IS NOT BROKEN DOWN BY THOSE PATIENTS WHO ACTUALLY WENT ONTO ENROLL IN TRIAL. WE HOPE TO DO THAT AT A LATER TIME. IT'S INTERESTING TO SEE THERE ARE INDIVIDUALS, 17% WHO HAD INCOMES LESS THAN 25,000. AND THEN THERE WERE 18% OF THE 8,000 WHO REFUSED TO PROVIDE THAT INFORMATION. THIS IS AN INTERESTING POINT BECAUSE WE HAVE WITHIN OUR PORTFOLIO OF CANCER CARE DELIVERY RESEARCH FINANCIAL TOXICITY TRIALS AND IT WAS VERY INFORMATIVE FOR US BECAUSE OFTEN SOMETIMES IT WAS THE PATIENTS BUT THE BARRIER ACTUALLY WAS IN THE HEALTH CARE PROVIDERS. AND THEIR LEVEL OF COMFORT AND ASKING THAT INFORMATION HOW IT SHOULD BE ASKED AND WE DID HAVE WEBINARS AND OTHER INTERVENTIONS TO HELP OUR HEALTH CARE TEAMS ASK THOSE QUESTIONS IN AN APPROPRIATE AND CULTURALLY SENSITIVE MANNER. WE ALSO LOOKED AT EDUCATION. WE SEE THAT WE ASK WHAT'S THE HIGHEST LEVEL OF EDUCATION, WE CAN SEE THAT THERE ARE ABOUT 28% OF THAT NUMBER OF PATIENTS WHO HAD A HIGH SCHOOL OR LESS EDUCATION SO IT'S GIVEN US A LITTLE BIT OF INFORMATION AND WE THINK ABOUT THESE THINGS WHEN WE THINK ABOUT OUR INTERVENTIONS ASSESSING FOR FEASIBILITY, WHAT WILL WORK IN SPECIFIC COMMUNITIES. NOW I'M GOING TO TURN TO EFFORT TO INCREASE EFFICIENCY AT CONCEPT AND PROTOCOL LEVEL. WE HAD WEBINARS WITH OUR RESEARCH BASE P.I.s AS WELL AS STATISTICIANS TO GET FEEDBACK. GIVEN THE FACT THAT WITH THE CONSOLIDATION, CERTAINLY THE NCTN GROUPS NEEDED TO COME TOGETHER WITH THEIR VARIOUS PORTFOLIOS FOR OUR RESEARCH AND HOW THEY WERE GOING TO WORK TOGETHER. THE FACT THAT WE HAVE SUCH A BROAD PORTFOLIO AND TYPES OF TRIALS. SO WHAT WE CAME UP WITH WAS THE TARGET TIME LINE, SO FROM THE CONCEPT RECEIPT AT NCI AND PROTOCOL INFORMATION OFFICE TO TIME OF APPROVAL, 120 DAYS. PROTOCOL AUTHORING, 90 DAYS. PROTOCOL REVIEW AND APPROVAL 175 DAYS. AND FROM PROTOCOL APPROVAL TO ACTIVATION, 90 DAYS. OUR OVERALL TARGET, TOTAL TARGET TIME, WAS 475 DAYS. SO, AS I MENTIONED, WE HAVE VARIOUS SOURCES FROM WHICH THE CONCEPT CAN EMANATE. FOR THOSE THAT RESEARCH THE CONCEPT THAT WE RECEIVED A PROTOCOL ACTIVATION, TARGET WAS 475. BUT THE ABSOLUTE WAS 525 DAYS WHICH IS OUR PROPOSAL THAT WAS IMPLEMENTED IN AUGUST 1 OF THIS YEAR. AND THIS ALLOWS FOR ONE REVISION AT THE PROTOCOL LEVEL. I THINK MY COLLEAGUES AT NCTN HAVE BEEN TALKING ABOUT THIS AS WELL. THERE WERE TOO MANY REVISIONS AT THE PROTOCOL LEVEL SO WE'RE TRYING TO MINIMIZ THAT AND GIVING 50 DAYS, 30 DAYS FOR THE LETTER REVISION AND TO COME BACK IN WITH CONSENSUS LETTER TO THE TIME OF APPROVAL ON WHOLE PRIOR TO GOING TO THE CENTRAL IRB TO -- FOR THAT TO REALLY GIVE US THE ABSOLUTE DAYS OF 525. FOR THOSE STUDIES THAT COME IN AS PROTOCOLS FOR EXAMPLE FROM THE RPG POOL LESS AMOUNT OF TIME BUT ALSO GIVING THEM THE TIME OF ONE REVISION AT THE PROTOCOL LEVEL AS WELL. SO, I'M CLEARLY NOT GOING THROUGH ALL THESE STUDIES BUT WANT TO END ON THIS SLIDE TO SHOW TO YOU I THINK 10 OR 11 STUDIES THAT WERE ACTIVATED AND COMPLETED THEIR TARGET ACCRUAL WITHIN THE TIME OF THE NCORP EXISTENCE REFLECTING OUR EFFICIENCY AND IDENTIFYING OF AREAS AS WE MOVE FORWARD. SO WE'RE GOING TO LOOK AT IMPLEMENTATION OF THESE TARGET DEADLINES IN EARLY 2019 GIVING US SIX MONTHS TO ASSESS AND THEN HAVING HAD ONE CYCLE OF UNDERSTANDING SCOPE OF RESEARCH WILL MAKE OUR ADDITIONAL PLANS TO IMPROVE EFFICIENCY SO ON THAT I'M GOING TO CLOSE AND I'M HAPPY TO TAKE ANY QUESTIONS. >> THANKS. WE HAVE A FEW MINUTES FOR QUESTIONS. I ASKED JIM AND SHEILA AS I WAS GETTING READY TO CHAIR THIS THING, THIS MEETING, WAS REALLY TRY TO CHARGE THE COMMITTEE WITH HAVING A PURPOSE. SO WITH EVERY PRESENTATION RATHER THAN JUST LISTENING TO PRESENTATIONS HOW CAN WE ADVISE YOU IN THE NCI AND I THINK FOR THIS THE TALKING POINTS, THEY BASICALLY SAID TO ASK WHETHER OR NOT WE FELT AS A COMMITTEE WHETHER THE NCORP CORE PERFORMANCE WAS MEETING EXPECTATIONS FOR THE FEDERALLY FUNDED CLINICAL TRIALS ENTERPRISE AND I THINK IT SEEMS LIKE AN EASY QUESTION TO ANSWER BUT I WOULD LIKE TO OPEN THIS UP FOR QUESTIONS FORWARD ABOUT NCORP AND THE MISSION. ANY QUESTIONS YOU HAVE? YES? >> I'D LIKE TO ASK IF THERE'S BEEN ANALYSIS ABOUT COMPLETERS. A COMMENT WAS MADE WHEN YOU SHOWED THAT ONE BAR OF THE PEOPLE ENROLLED, FOR EXAMPLE, IT WAS ONE EXAMPLE OF YOUR MULTIPLE PRESENTATIONS WHICH I TOTALLY APPRECIATE BUT OF THE INCOME AND HOW THAT -- SO FROM MY PERSPECTIVE, WHAT'S IMPORTANT IS GETTING THE DATA BACK AND LEARNING FROM THE DATA. AND IF CERTAIN BAR IS LOWER THAN ANOTHER BAR BUT THERE'S 90% COMPLETER RATE WHEREAS THE BAR FOR INITIAL ENROLLMENT HAS 70% COMPLETER RATE, YOU GET MORE DATA BACK FROM BAR NUMBER TWO VERSUS -- YOU KNOW, ONE BAR VERSUS THE OTHER. SO I MEAN THIS IS A PROBLEM THAT I KNOW IT'S A PROBLEM WITH INDUSTRY. WHEN I WAS IN COOPERATIVE GROUPS IT WAS A PROBLEM WITH COOPERATIVE GROUPS. MISSING DATA, PEOPLE WHO ARE ENROLLED AND COUNT AS ENROLLMENT METRIC BUT DON'T COMPLETE THE TRIAL WITH SUFFICIENT DATA TO -- YOU CAN DEFINE IT VARIOUS WAYS, TYPICALLY WE DEFINE IT AS ENOUGH FOR A VALUABLE AT LEAST PRIMARY AND MAJOR SECONDARY ENDPOINTS. IF YOU'RE MISSING DATA FROM SOMETHING AND THEY DON'T COMPLETE SOME MINOR ISSUE, YOU KNOW, CAN YOU FORGIVE THAT MORE BUT IF YOU DON'T HAVE THE RIGHT DATA FOR THE PRIMARY ENDPOINTS AND MAJOR SECONDARY ENDPOINTS THEN YES THEY DO COUNT ENROLLMENT BUT YOU UNDERSTAND WHAT I'M SEEKING HERE? >> YEAH, RIGHT. I THINK THERE ARE VARIOUS INTERVENTIONS THAT ACTUALLY LOOK AT THAT INCLUDING THE DATA SAFETY MONITOR. ONE EXAMPLE WE HAD ISSUES WITH COMPLETING IN THE QUALITY OF LIFE, BUT WE HAVE MADE MEASURES TO TRY TO IMPROVE THAT, ONE OF WHICH WAS TO INCLUDE IT IN AUDITING BECAUSE IT HAD NOT BEEN NECESSARILY IN THE AUDIT. SO I THINK THAT'S ONE GOOD EXAMPLE BUT YOUR POINT IS WELL TAKEN. >> I WAS GOING TO ASK A QUESTION. I FORGOT COLLINS WROTE THIS BOOK, ONE OF THE ANALYSIS IS THAT A GREAT COMPANY DECIDES WHAT THEY AREN'T GOING TO DO. AS I LOOK THROUGH THIS AND THINK ABOUT THE EFFORT FOR THE TISSUE ACQUISITION STUDIES WITH 276 PATIENTS, AND I LOOK WHERE THEY CAME FROM, THEY DIDN'T COME FROM MINORITIES OR ANYTHING, I'M WONDERING WHETHER THIS IS SOMETHING THAT'S REALLY WORTHWHILE AS PART OF THE NCORP, WHETHER IT SHOULD BE COMING FROM THE CANCER CENTERS THEMSELVES. WE MIGHT GET MAYBE -- IS IT WORTH IT FOR THIS PROGRAM TO HAVE THAT IN THERE? >> ACTUALLY THERE WAS A SECOND REISSUANCE SPECIFICALLY FOR MINORITY SITES, ONE OR TWO IN THE ORIGINAL COHORT AS WELL. THE PROJECT THAT'S LOOKING AT SEQUENCING IN CONJUNCTION WITH CENTER FOR CANCER GENOMICS FOR EARLY ONSET IS EXCLUSIVELY IN MINORITY UNDERSERVED SITES. >> THE OTHER QUESTION IN TERMS OF MINORITY ACCRUAL THERE'S 20% ACCRUAL. >> ACROSS THE BOARD, YES. >> I DIDN'T SEE THE SPLIT BETWEEN THE ONES FOR CANCER TREATMENT AS WELL AS CANCER CONTROL, WHETHER OR NOT -- AT LEAST AT OUR CENTER IT'S THE ONES WHO GO ON THE NON-THERAPEUTIC TRIALS, THERE'S A HIGHER PERCENTAGE OF, SAY, AFRICAN-AMERICAN MINORITIES BUT THE TREATMENT TRIAL STILL IS LOW. HAVE YOU SEEN DIFFERENCES THERE? IT'S NOT SPLIT OUT HERE. >> NO, I DON'T. I THINK WE HAVE BUT I CAN'T QUOTE IT AT THIS TIME, BUT I DO REMEMBER THAT SOME OF THE SYMPTOM TRIALS, WE'VE LOOKED AT IT SOMETIMES, DEPENDS UPON WHAT IT IS, SOMETIMES COMORBIDITIES THEY ARE NOT ELIGIBLE BECAUSE OF THAT. AS A MATTER OF FACT, WE HAD A RECENT DISCUSSION ABOUT THAT BECAUSE AS WE LOOKED AT THOSE PATIENTS WHO WERE NOT ELIGIBLE, WE DIDN'T LOOK AT TERMS OF RACE AND ETHNICITY BUT SOME WERE HIGHER IN SYMPTOM TRIALS, SOME BECAME MORE COMPLEX, BUT YET THEY MAY NEED TO BE THERE BECAUSE THEY MAY HAVE UNDERLYING CHRONIC DISEASES. BUT THAT'S ONE OF THE THINGS WE WERE GOING TO LOOK AT IN PREPARING OUR PUBLICATIONS TO BEING MORE DETAILED ABOUT THAT. >> BUT ONE OF THE THINGS, JUST TO ADD TO THE POINT, ONE OF THE THINGS WE STARTED DOING IN OUR STEERING COMMITTEE BECAUSE OF THAT VERY THING IS HAVING ONE OF THE MINORITY UNDERSERVED REPRESENTATIVES ON THE STEERING COMMITTEE REVIEW ALL ELIGIBILITY CRITERIA AND EVEN THE STUDY FROM THE LENS OF IS THIS FEASIBLE, ARE THERE RED FLAGS THAT WOULD SYSTEMATICALLY ELIMINATE MINORITIES OR UNDERSERVED FROM THE PROTOCOL AND I THINK IT'S TOO EARLY TO SAY WHETHER THAT'S CHANGING ANYTHING, BUT I DO THINK THAT IS AT LEAST TO PUT IT IN THE WORKFLOW, TO MAKE SURE THERE AREN'T SYSTEMATIC THINGS, AT LEAST ONE STEP. >> SO I'M GOING TO SPEAK ON BEHALF OF THE PEDIATRIC SITE. WITHIN NCORP THERE ARE THREE SOLELY PEDIATRIC NCORP, AND WHAT WE'VE BEEN FACING IS REALLY A DWINDLING OF THE CLINICAL TRIAL PORTFOLIO THROUGH COG. THERE'S A LIMITED NUMBER OF THERAPEUTIC TRIALS. OUR ENROLLMENTS KIND OF GO UP AND DOWN BASED ON THE LEUKEMIA STUDIES, PORTFOLIO FOR CANCER CONTROL STUDY SYMPTOM MANAGEMENT IS EXTREMELY LIMITED. I THINK WE'RE DOWN TO ONE OR TWO, AND MOSTLY IN THE TRANSPLANT SETTING. SO WE ARE REALLY KIND OF LIMITED. THE OTHER ISSUE I WENT TO THE NCORP MEETING THIS PAST WEEKEND, AND AT THE LEVEL OF THE STATE THEY WILL NOT BE ABLE TO PARTICIPATE IN NEUROBLASTOMA STUDIES BECAUSE THERE ARE NO MRBG SITE WITHIN THE STATE AND SO PATIENTS WHO ARE COVERED BY MEDICAID NEED TO BE GOING TO ANOTHER STATE AND THEN YOU HAVE THE QUESTION OF THIRD PARTY PAYER. SAME THING WITH THE NEW PROTOCOL THAT IS COMING FROM THE VERY HIGH RISK A.L.L. WHERE CAR T CELL IS GOING TO BE MANDATED FOR THE VERY HIGH RISK, BUT IT CAN ONLY BE DONE AT SHOP, PER PROTOCOL. AND, AGAIN, THEY WILL NOT BE ABLE TO SEND THEIR PATIENTS OUTSIDE OF THE STATE. SO, THESE PROTOCOLS I THINK WHAT WE HAVE ELECTED TO DO, START DOING IN JANUARY THROUGH COG IS REALLY HOLD WEBINARS WHERE WE CAN REVIEW CONCEPTS FOR IMPLEMENTABILITY AND KIND OF VETTING BEFORE THEY GO FORWARD BOTH FOR, YOU KNOW, SOME OF THE THERAPEUTIC STUDIES AND OF COURSE FOR THE CANCER CONTROL STUDIES, WE'VE ALSO HAD STUDIES WHERE WE COULD NOT ENROLL ANYBODY WHO DIDN'T SPEAK ENGLISH BECAUSE THE TOOLS THAT WERE USED TO ASSESS OUTCOME WERE NOT VALIDATED IN ANY OTHER LANGUAGE SO THAT ESSENTIALLY BLOCKED THOSE PATIENTS FROM ENROLLMENT. SO WE ARE -- WE REALLY ARE FACING A CRISIS. WE DON'T HAVE THAT MANY CLINICAL TRIALS. >> THE FINAL QUESTION TO YOU. WHAT QUESTIONS DO YOU HAVE FOR US, HOW CAN THIS COMMITTEE HELP YOU? >> WELL, I THINK WE LIKE TO HAVE, YOU KNOW, ADVISEMENT I THINK FROM ACROSS THE BOARD. I MEAN, MOST OF THE CARE IS DONE IN THE COMMUNITY SETTING SO THE ABILITY FOR US TO CONDUCT THEM SUCCESSFULLY IS REALLY IMPORTANT. I THINK WE TRIED TO IDENTIFY CERTAINLY AREAS OF PREVENTION WHETHER WE HAVE SOME GAPS BUT WE'D JUST LIKE TO HEAR, YOU KNOW, HOW WE CAN BETTER COLLABORATE WITH MANY OF YOU WHO ARE IN THE ACADEMIC PART OF IT. NCORP IS A COMMUNITY ACADEMIC PARTNERSHIP, AND HOW YOU THINK THAT WE CAN MAKE CHANGES THAT WOULD HELP TO STRENGTHEN THAT WOULD BE HELPFUL. >> I THINK THAT ONE OF THE ASPECTS WE'VE DISCUSSED AS PART OF THE NCORP IS PARTICIPATION OF THE COMMUNITY PRACTITIONERS IN SOME OF THESE PROTOCOLS, ESPECIALLY THE CANCER PREVENTION SYMPTOM MANAGEMENT PROTOCOLS BECAUSE THE REALITY IS THAT IN THE INITIAL DIAGNOSIS, ANY PREVENTION MEASURES OR ESPECIALLY SYMPTOM MANAGEMENT FOR SOME OF THE PATIENTS THAT COMPLETED TREATMENT AT THE CANCER CENTERS IS DONE BY COMMUNITY PRACTITIONERS AND WHEN YOU CONSIDER PARTICIPATION OF MINORITY PATIENTS OR UNDERSERVED PATIENTS IN RULE AREAS, FOR EXAMPLE, WHERE MANY OF OUR PATIENTS COME FROM, IT IS REALLY THE COMMUNITY PRACTITIONER WHO LEADS THIS, NOT THE ONCOLOGIST. THERE ARE A FEW ONCOLOGISTS IN THESE RURAL AREAS. SO I THINK ONE OF THE CONVERSATIONS THAT WE'VE INITIATED AT LEAST INFORMALLY WITHIN THE NCORP IS HOW CAN WE INCORPORATE THESE COMMUNITY PRACTITIONERS, THESE COMMUNITY GROUPS, THE FQHCs AND THING OF THAT SORT THAT CAN HELP US IN THE DEVELOPMENT OF THOSE PROTOCOLS. THINK THAT ALSO MIGHT FURTHER INCREASE THE PARTICIPATION OF MINORITY AND UNDERSERVED POPULATIONS AND WE'VE HAD SOME OF THESE DISCUSSIONS BUT I THINK IT'S BEEN IMPLEMENTED MORE ON AN INDIVIDUAL SITE BUT AS A PROGRAM THAT MIGHT BE SOMETHING TO AIM TOWARDS. >> THANK YOU. NEXT UP, GISELLE IS A MEDICAL CENTER, COORDINATING CENTER FOR CLINICAL TRIALS UNIT. THIS IS -- HER PRESENTATION IS TO PROVIDE AN UPDATE ON THE ONGOING ACTIVITY OF THE NCI FOR TRYING TO IMPROVE CLINICAL TRIALS. THE CLINICAL TRIALS INFORMATICS WORKING GROUP -- THIS WAS A TOPIC FOR THEM AND NCI RELEASED AN RFI FOCUSING ON STRATEGIES IN ORDER TO HELP MATCH PATIENTS IN CLINICAL TRIALS. WE'RE GOING TO ASK THIS GROUP TO GIVE ADDITIONAL COMMENTS ON THE STRATEGIES THAT HAVE BEEN IDENTIFIED BY THIS RFI AND WHETHER WE SHOULD CONSIDER SOME ADDITIONAL FACTORS FOR CONSIDERATION. GISELLE? >> OKAY. WELL, THANK YOU VERY MUCH. THANK YOU FOR THE INVITATION TO SPEAK THIS AFTERNOON. IT'S A PRIVILEGE TO PRESENT ON BEHALF OF THE FINDING CANCER TRIALS COLLABORATIVE, A GROUP OF STAFF THROUGHOUT NCI INCLUDING STAFF IN COLLABORATION WITH PRESIDENTIAL FELLOWS, MANY IN THE AUDIENCE PARTICIPATING VIA VIDEOCAST WORKING TO IDENTIFY APPROACHES TO MAKING CANCER CLINICAL TRIALS EASIER TO FIND. IN MY PRESENTATION, I'M GOING TO COVER THREE AREAS. FIRST, WHAT THE CHALLENGE IS, SECOND BACKGROUND ON NCI CLINICAL TRIALS REPORTING PROGRAM WHICH MAY BE A RESOURCE THAT MAY HELP US AS WE'RE TRYING TO ATTEMPT TO SOLVE THIS CHALLENGE, AND THIRDLY AN UPDATE ON ACTIVITIES OF THE GROUP WORKING ON THIS PROBLEM. FINDING CANCER CLINICAL TRIALS IS COMPLEX. PATIENTS AND PROVIDERS HAVE A COMMON NEED, TO FIND THE CANCER OR TRIAL THEY NEED. BUT THEY HAVE DIFFERENT WAYS OF LOOKING FOR TRIALS. SECONDLY, THERE ARE MULTIPLE SOURCES OF INFORMATION. SO IT'S HARD TO KNOW WHICH ONE OR ONES YOU SHOULD GO TO. SEARCHING RETRIEVE TOO MANY TRIALS FOR WHICH A PATIENT IS INELIGIBLE AND ONCE YOU'VE DONE THE SEARCH THE LIST OF TRIALS THAT ARE RETURNED IS NOT SUFFICIENTLY PRECISE. YOU MAY WIND UP GETTING TRIALS THAT ARE NOT RELEVANT TO THE PATIENT OR PARTICIPANT, OR YOU MAY MISS ONES THAT ARE RELEVANT PARTICULARLY THOSE THAT ARE IN THE FIELD OF PRECISION MEDICINE OR BASED ON MOLECULAR ABERRATION. AND THIS CHALLENGE WAS POINTED OUT DURING THE MOONSHOT WHERE IN THE SUMMIT THEY SAID PATIENTS SHOULD BE ABLE TO SEAMLESSLY FIND A CLINICAL TRIAL THAT MIGHT SUIT A SPECIFIC CONDITION. SO, THIS IS A PICTORIAL ATTEMPT TO TRY TO SHOW WHAT OUR VISION IS. AND WHAT WE'RE TRYING TO DO IS MAKE IT EASY AND SEAMLESS TO FIND THE CLINICAL TRIAL YOU NEED OR PATIENT NEEDS AT THE POINT OF NEED. THIS ICON SHOWS THE POINT OF TIME BETWEEN DIAGNOSIS AND TREATMENT WHERE A PATIENT AND PROVIDER MAY BE LOOKING FOR TREATMENT TRIAL BUT IF YOU CAN IMAGINE SLIDING THIS ICON TO THE LEFT OR TO THE RIGHT, YOU COULD JUST AS WELL BE A PERSON OR A PROVIDER WHO IS LOOKING FOR PREVENTION TRIAL, SCREENING TRIAL, OR DURING TREATMENT LOOKING FOR SUPPORTIVE CARE TRIAL. SO IT'S REALLY NOT TREATMENT SPECIFIC BUT WHERE IN TIME YOU NEED A TRIAL AND GETTING THE TRIAL TO YOU SEAMLESSLY AT THAT TIME. THIS SHOWS OUR VISION IN SOMEWHAT GREATER DETAIL, AS WE ALL KNOW THE NCI CLINICAL TRIAL SEARCH ENTERPRISE CONSISTS OF MULTIPLE INTERRELATED PARTS. IT'S A BUSY SLIDE. LET ME DRAW YOUR ATTENTION TO THE LEFT SIDE WHICH IS TRIAL INFORMATION. AND THE BOX ON THE RIGHT SIDE, PATIENT INFORMATION. AND THEY BOTH NEED TO COME TOGETHER THROUGH A SEARCH ALGORITHM TO FIND -- TO PRODUC THE LIST OF TRIALS. CURRENTLY WE HAVE UNSTRUCTURED PROTOCOL DOCUMENTS THAT ULTIMATELY GET INTO A DATABASE THAT ULTIMATELY GO OUT THROUGH AN API AND ARE PROVIDED TO THIRD PARTY USERS. WHAT'S IMPORTANT ABOUT THIS GRAPHIC IS THAT ANY CHANGES WE MAKE TO PATIENT INFORMATION TO IMPROVE THIS PROBLEM WE WANT TO BE INFORMED BY HOW WE CRAFT THE PATIENT INFORMATION BECAUSE THE ULTIMATE VISION MIGHT BE TO HAVE PATIENT INFORMATION AND PROTOCOL INFORMATION MATCH SEAMLESSLY FROM EHR INFORMATION. AND SO IF WE START MAKING CHANGES ON THE LEFT WITHOUT BEING INFORMED BY THE RIGHT, WE MAY GET INTO TROUBLE. SO, NEXT I'D LIKE TO GET SOME BACKGROUND ABOUT CTRP, YOU MAY BE FAMILIAR BECAUSE I PRESENTED TO THIS GROUP PREVIOUSLY BUT IT'S A DATABASE CONTAINING REGULARLY UPDATED INFORMATION ON ALL NCI-SUPPORTED TRIALS, INCLUDING THOSE UNDERTAKEN AT DESIGNATED CANCER CENTERS USING ABSTRACTION, IT SUPPORTS REGISTRATION AND RESULTS REPORTING OF NCI-SPONSORED TRIALS TO clinicaltrials.gov. AND IT'S THE SOURCE OF DATA FOR NCI'S CLINICAL TRIALS SEARCH TOOL ON THE CANCER. CANCER.GOV WEBSITE. WHAT MAKES IT DIFFERENT FROM OTHER REPOSITORIES? AGAIN, IT'S THE CONSISTENT TERMINOLOGY AND STANDARDIZED DATA ELEMENTS. ACCRUAL IS REPORTED TO CTRP AT LEAST QUARTERLY. STANDARD REPRESENTATION OF PERSONS AND ORGANIZATIONS AND BEFORE I STARTED WORKING ON CTRP I HAD NO IDEA HOW THE SAME ORGANIZATION COULD BE REPRESENTING A MILLION DIFFERENT WAYS. OUR BRAIN KNOWS THAT'S ALL THE SAME THING BUT A COMPUTER DOESN'T. SO WHAT MAKES CTRP UNIQUE IS THAT EACH TIME THE ORGANIZATION IS REPRESENTED, IT'S REPRESENTED IN A STAND AROUND WAY. LIKEWISE EACH PERSON IS REPRESENTED AS A UNIQUE INDIVIDUAL. INCLUSION OF STRUCTURED BIOMARKER INFORMATION, IDENTIFICATION ASSOCIATED NCI AWARD AND CONTRACTS, AND REGULAR UPDATES WE STRIVE TO MAKE DATA AS CURRENT AS POSSIBLE AND THROUGH INTEGRATION WITH SYSTEMS MAINTAINED AND DEVELOPED BY CTEP AND DCEP, WHICH CAN BE MULTIPLE SITES. SO THE TRIALS INCLUDED IN CTRP THE SCOPE ARE INTERVENTIONAL CLINICAL TRIALS, SUPPORTED BY NCI, INCLUDING ALL TAKING PLACE IN NCI DESIGNATED CANCER CENTERS INCLUDING THE INDUSTRIAL TRIALS. TRIALS SPONSORED BY NCI PER FDAAA, AS WELL AS BY OTHER ENTITIES, CURRENTLY REPORTING OF OBSERVATION AND CORRELATIVE STUDIES IS OPTIONAL. IN AN ANALYSIS UPDATED IN SEPTEMBER LAST MONTH, THE MONTH BEFORE LAST, SEPTEMBER 2018, 90% OF THE INTERVENTIONAL CANCER CLINICAL TRIALS OPEN TO PATIENT ACCRUAL IN THE UNITED STATES FOUND IN clinicaltrials.gov ARE ALSO IN CTRP. THIS SLIDE SHOWS HOW DATA IN CTRP IS DISTRIBUTED TO THE WORLD AT LARGE. WE HAVE AN APPLICATION PROGRAMMING INTERFACE WHICH IS A COMPUTER CONNECTION BETWEEN DATA IN CTRP WHICH FUELS cancer.gov WEBSITE AND SEARCH TOOL, BUT ALSO MADE AVAILABLE TO THIRD PARTIES AND THIRD PARTY INNOVATORS SUCH AS ACADEMICS, ADVOCACY ORGANIZATIONS, INDUSTRY, WHO CAN TAKE THE DATA THROUGH THE API AND REPACKAGE IT AND REUSE IT FOR THEIR OWN PURPOSES. SO WITH THAT AS A BACK DROP I'D LIKE TO BRING AN UPDATE REGARDING ACTIVITIES OF WHAT WE CALL THE FINDING CANCER TRIALS COLLABORATIVE. AND FIRST I SHOULD STATE THAT FOR THE CANCER CLINICAL TRIALS SEARCH ON cancer.gov, IN 2017 WE TRANSITIONED TO CTRP AS THE DATA SOURCE. WHEN YOU GO TO THE NCI WEBSITE, ANY SEARCH DONE ON EITHER BASIC OR ADVANCED FORM RETURNS DATA FROM CTRP. FURTHERMORE ADDITIONAL ENHANCEMENTS THAT HAVE BEEN MADE SINCE THAT TIME INCLUDE CHAT BOX HELP, INTEGRATION WITH NCI SOURCE, VOCABULARY TO IMPROVE SEARCH ACCURACY SO WHEN YOU SEARCH FOR A SPECIFIC DISEASE THIS RESOURCE CAN HELP FIND THE DISEASE YOU'RE LOOKING FOR AND TYPE AHEAD, MULTI-SELECT OPTIONS TO IMPROVE THE USER EXPERIENCE. A LARGE PART OF THE EFFORT OVER THE PAST YEAR IN COLLABORATION WITH THIS LARGE GROUP OF PEOPLE THROUGHOUT NCI HAS BEEN GATHERING INFORMATION AND ENGAGING STAKEHOLDERS. I THINK IT WAS ABOUT A YEAR AGO THE CTAC GROUP PRESENTED TO THIS GROUP, AN IMPORTANT SOURCE OF INFORMATION ON THIS EFFORT. WE HELD A SERIES OF TELECONFERENCES AND MEETINGS WITH PEOPLE AND STAKEHOLDERS, ORGANIZATIONS, WE KNEW WHO WERE INTERESTED AND INVOLVED IN THIS EFFORT, TO BE COMPLETE WE ISSUED A REQUEST FOR INFORMATION SO THAT THOSE WHOM WE DID NOT KNOW ABOUT WHO WERE INTERESTED IN THIS HAD AN OPPORTUNITY TO PROVIDE INFORMATION TO US ABOUT THEIR ACTIVITIES IN THIS AREA. AND LASTLY WE'VE BEGUN A COLLABORATION WITH DATA SCIENTISTS THROUGH THE PRESIDENTIAL INNOVATION FELLOWS. SO LAST YEAR THE CLINICAL TRIALS GROUP IDENTIFIED STRUCTURING ELIGIBILITY FOR IMPROVING CLINICAL TRIALS SEARCH. THEY NOTED MANY HAD ATTEMPTED TO DO SO WITH LIMITED SUCCESS AND SOME DISEASE AND HEALTH CARE SETTINGS BUT TO DATE NO EFFORTS HAVE SYSTEMICALLY STRUCTURED ELIGIBILITY IN A STANDARDIZEDs FASHION FOR USE BY THE BROAD CANCER CLINICAL TRIAL COMMUNITY. SO WHAT IS MEANT BY STRUCTURING? I THINK IN A PREVIOUS SLIDE I HAD SHOWN YOU THE TRIAL INFORMATION AND PATIENT INFORMATION. THIS SLIDE EMPHASIZES OR SHOWS ONLY THE TRIAL INFORMATION. AND THE CURRENT WAY THINGS WORK IS PROTOCOL DOCUMENT COMES TO US TYPICALLY WRITTEN IN WORD, WITH LIMITED STRUCTURE, AND PARTICULARLY THE ELIGIBILITY CRITERIA ARE UNSTRUCTURED EXCEPT FOR ONE OR TWO DATA ELEMENTS SUCH AS AGE. ABSTRACTERS ADD ADDITIONAL STRUCTURE, BE A TRACTS GOING INTO THE CTRP DATABASE AND ARE MADE AVAILABLE. SO IF WE WERE TO STRUCTURE THEM WE EXPRESS INFORMATION IN PROTOCOL DOCUMENT SUCH AS ELIGIBILITY CRITERIA IN A CONSISTENT FORMAT. WE READ THROUGH THAT TEXT, ISOLATE WHAT THAT CRITERIA IS AND EXPRESS THE SAME WAY. APPROACHES INCLUDE DOING IT AT THE POINT OF PROTOCOL AUTHORING, OR, B, APPLYING STANDARD ONTOLOGY OR TERMINOLOGY TO ELIGIBILITY CRITERIA. THIS COULD BE DONE BY HUMAN ABSTRACTERS AND ONCE YOU FIGURE OUT HOW TO DO IT YOU COULD POTENTIALLY USE NATURAL LANGUAGE PROCESSING OR ARTIFICIAL INTELLIGENCE TO IMPROVE EFFICACY. AND WHEN THEY SAY A PICTURE IS WORTH A THOUSAND WORDS THIS SHOWS WHAT I TRIED TO EXPLAIN. THESE ARE THREE DIFFERENT STUDIES WITH ELIGIBILITY CRITERIA THAT MEAN THE SAME THING, EXPRESSED IN WORDS, IN VERY DIFFERENT WAYS. SO A PERSON WOULD NEED TO READ THROUGH THEM, I THINK IT WOULD BE BEYOND OUR CURRENT EXPERIENCE WITH MACHINE LEARNING OR COMPUTERS TO BE ABLE TO DO IT IN AN AUTOMATED FASHION BUT A PERSON READS THROUGH IT AND SAYS, I UNDERSTAND, WHAT THEY ARE SAYING IS PARTICIPANT HIV, USING ANTIRETROVIRAL TREATMENT IS EXCLUDED. ON THE RIGHT CRITERIA PUT INTO COMPUTER CODE FOR DEMONSTRATION WE'VE USED THE CODES THAT ARE IN NCI THESAURUS BUT A COMPUTER COULD UNDERSTAND WHAT'S ON THE RIGHT COLUMN, A COMPUTER CAN'T UNDERSTAND WHAT'S ON THE LEFT. AND ARGUABLY ON THE LEFT IS ONE OF MANY ELIGIBILITY CRITERIA THAT RIGHT NOW WE HAVE TO STRUGGLE THROUGH WHEN WE'RE TRYING TO EVALUATE A POTENTIAL PARTICIPANT. IT WAS RECOMMENDED WE STRUCTURE ELIGIBILITY CRITERIA, WE HAD A SERIES OF TELECONFERENCES AND MEETINGS WITH STAKEHOLDERS. IF YOU CAN EXPRESS THEM IN A CONSISTENT WAY IT WILL MAKE IT EASIER TO FIND TRIALS. EFFORTS TO IMPROVE SEARCH OR MATCH PATIENTS TO TRIALS TO DATE HOWEVER WERE LIMITED BY LACK OF STANDARDS, WHAT CODE SHOULD YOU USE, HOW TO DESCRIBE THESE CRITERIA, EXTENSIVE HUMAN CURATION IS CURRENTLY INVOLVED FOR THE REASONS I JUST DESCRIBED. THE STAKEHOLDER ENGAGEMENT SUGGESTED NCI TAKE THE LEAD IN STRUCTURAL ELIGIBILITY CRITERIA BECAUSE THESE TELECONFERENCES NOTED THAT NCI WAS VIEWED AS HONEST BROKER FOR IDENTIFYING AN APPROACH TERMINOLOGY AND STANDARDS AND MANY WERE ENTHUSIASTIC THAT NCI WAS TALKING ABOUT THIS. WE THEN ISSUED A REQUEST FOR INFORMATION WITH RESPONSE PERIOD THAT ENDED SHORTLY AFTER ASCO SO THEY KNEW AND HAD THE OPPORTUNITY TO REPLY IF THEY CHOSE TO DO SO. AND THE RFI REQUESTED INFORMATION ABOUT WHAT AND HOW TO STRUCTURE ELIGIBILITY CRITERIA, ETHODS AND MODELS TO SEARCH OR MATCH PATIENTS TO TRIALS, TECHNOLOGIES, APPROACHES TO COLLABORATION, COULD THE STRUCTURING OF ELIGIBILITY CRITERIA AND MATCHING HOW BE INCENTIVIZED. WE GOT 39 RESPONDENTS. AS YOU CAN SEE PRIVATE SECTOR COMPANIES WERE 15, ACADEMICS ORGANIZATIONS 13. SO OTHER OVERARCHING CONSIDERATIONS THAT CAME THROUGH IN THE RFI IS THAT IT'S DIFFICULT TO STRUCTURE ELIGIBILITY CRITERIA AND HAD THIS PROBLEM BEEN EASIER SOMEBODY WOULD HAVE SOLVED IT FOR THE COMMUNITY BY NOW. SECONDLY, SET REALISTIC TIMEFRAMES BECAUSE IT'S GOING TO BE HARD. THREE, INVOLVE EXPERTS AND CHANGE MANAGEMENT IN HUMAN CENTERED DESIGN AS WE MOVE FORWARD. AND THAT STRUCTURING IS FUNDAMENTAL FOR REASONS I'VE DESCRIBED TO ENABLE TECHNOLOGY FIELD SOLUTIONS. AND THEN OTHER COMMON THEMES WERE STANDARD AND STRUCTURED ELIGIBILITY CRITERIA SHOULD BE DEVELOPED, AUTOMATED PROCESSES COULD BE USED. AND INTEROPERABILITY AND DATA STANDARDS ARE THE KEY TO MATCHING PATIENTS TO INFORMATION AND EHRs. ULTIMATELY PATIENT INFORMATION RATHER THAN COMING IN THROUGH CALLERS AND WEBSITES WHICH WE ALWAYS PROBABLY WILL WANT TO SUPPORT POTENTIALLY COULD COME THROUGH AN EHR. WE WANT TO BE SURE WHAT WE'RE DOING WILL MATCH UP WHEN WE GET THERE IN TIME. WE SHOULD -- FURTHER THEMES THAT NCI SHOULD CREATE AND ADOPT DATA STANDARDS FOR ELIGIBILITY CRITERIA, INTEGRATE CLINICAL TRIALS INTO THE CLINIC WORKFLOW, AND SUGGESTIONS FOR IMPROVING SEARCH BECAUSE WE DID INVITE FOR OTHER COMMENTS THAT SEARCH INTERFACES SHOULD BE USER SPECIFIC AND ELIGIBILITY CRITERIA AS WELL AS OTHER CLINICAL TRIAL INFORMATION SHOULD BE PRESENTED IN PATIENT FRIENDLY LANGUAGE. THIS IS AN OVERVIEW OF OUR COLLABORATION WITH DATA SCIENTISTS BECAUSE WE KNEW THAT COLLABORATING WITH ENGINEERS AND DATA SCIENTISTS FROM THE BEGINNING WOULD BE VERY IMPORTANT. SO IN COLLABORATION WITH THE PRESIDENTIAL INNOVATION FELLOWSHIP PROGRAM, WE PARTICIPATED IN NIH DATA SCIENCE HACKATHON ABOUT A MONTH OR TWO AGO. THESE ARE THREE-DAY EVENTS THAT BRING TOGETHER PEOPLE WHO DO COMPUTER PROGRAMMING AND COMPUTER SCIENTISTS GIVEN A SHORT PERIOD OF TIME TO WORK ON COMMON MON. THIS IS OUR UNSTRUCTURED ELIGIBILITY, GO AT IT FOR THREE DAYS AND COME UP WITH A NOVEL APPROACH HOW YOU CAN STRUCTURE IT. THEY CAME UP WITH INTERESTING OBSERVATIONS ABOUT FREQUENCY OF ELIGIBILITY CRITERIA. CURRENTLY, THE TOP HEALTH OR OPPORTUNITY PROJECT DONE IN COLLABORATION WITH DEPARTMENT OF HEALTH AND HUMAN SERVICES IS ONGOING, AND THIS IS A THREE-MONTH EVENT, THREE-MONTH PERIOD THAT WILL BRING TOGETHER LARGE COMPANIES TO WORK ON THE PROBLEM OF HOW TO STRUCTURE UNSTRUCTURED DATA AND POTENTIALLY MATCH IT TO PATIENT INFORMATION WITH THE GOAL OF PRESENTING THIS AT A MEETING TO BE SCHEDULED IN JANUARY. SO THERE'S OPTIMISM THERE MAY BE SOME PRELIMINARY OBSERVATIONS THAT COME OUT OF THE THREE-MONTH PERIOD. SO IN SUMMARY, MAKING CANCER CLINICAL TRIALS EASIER TO FIND IS A COMPLEX PROBLEM. TO SOLVE IT WILL REQUIRE ENGAGEMENT OF STAKEHOLDERS. THE CLINICAL TRIALS INFORMATICS WORKING GROUP RECOMMENDED NCI STRUCTURED ELIGIBILITY CRITERIA, CTRP COULD CONTRIBUTE TO THE SOLUTION BY ADDING ADDITIONAL STRUCTURE TO TRIAL REGISTRATION RECORDS BUT WE ALL ACKNOWLEDGE THAT STRUCTURING TRIAL INFORMATION IS ONLY PART OF SOLUTION. SO WHAT ARE OUR NEXT STEPS? WE'RE COMMUNICATING THE FINDINGS OF OUR LAST ANALYSIS TO NCI ADVISORY BOARDS, PRESENTED TO NCRA TWO WEEKS AGO. WE'RE HERE TODAY. WE'RE EXPLORING WITH OUR COLLEAGUES IN CTEP IF THERE'S APPROACH TO PROTOCOL FOR NCI NETWORK TRIALS, FOR EXAMPLE ETCTN TRIALS, AND WE WANT TO CONTINUE TO WORK WITH THE COMMUNITY AT LARGE TO FIGURE OUT HOW TO GO FORWARD ON TACKLING THIS COMPLEX PROBLEM. SO, IF I COULD GO TO THE LAST SLIDE. THIS IS JUST A PICTURE OF SOME OF THE MANY, MANY PEOPLE WHO HAVE BEEN INVOLVED IN THIS. BEFORE I WENT TO THE DISCUSSION I WANTED TO AGAIN SAY I'M PRESENTING BUT I'M REALLY DOING IT ON -- IT DOES TAKE A VILLAGE OR A CITY TO DO THIS, NOT JUST A VILLAGE. HOW DO I GO BACK? THE SLIDE BEFORE. THANKS. WITH THAT I'D LIKE TO OPEN TO DISCUSSION AND GET YOUR INPUT ABOUT WHAT I'VE JUST PRESENTED AND IF THERE ARE OTHER STRATEGIES OR FACTORS TO TAKE INTO CONSIDERATION. >> THANK YOU. ANY OTHER STRATEGIES OR FACTORS TO TAKE INTO CONSIDERATION? YES? >> I HAVE A QUESTION. I WANT TO MAKE SURE I UNDERSTOOD YOUR PRESENTATION. THIS IS AN ALTERNATIVE SEARCH ENGINE FOR CANCER PATIENTS TO FIND TRIALS THROUGH THE NCI cancer.gov WEBSITE. THERE SHOULD BE PRETTY MUCH 100% OVERLAP OF WHATEVER YOU HAVE IN YOUR SEARCH WITH clinicaltrials.gov, WHICH IS NOT AS USER FRIENDLY. IS THAT WHAT I'M GETTING HERE? AND ACCRUAL DATA THATSOME COMING FROM CANCER CENTERS IS AN ADDITIONAL PIECE IN YOUR ENGINE. IS THAT -- >> CORRECT. cncer.gov, CTRP HAS BEEN DEVELOPED TO MEET NCI PORTFOLIO MANAGEMENT NEEDS AND PROVIDES DATA TO NCI'S WEBSITE, CANCER.GOV. SO WE HAVE APPROXIMATELY 90% OF THE TRIALS THAT ALSO ARE IN clinicaltrials.gov BUT WE HAVE DIFFERENT -- WE HAVE THE ABILITY TO DIRECTLY MANAGE SOME OF THE CONTENT AND CHANGE SEARCH ALGORITHMS. >> IT'S ONLY NCI PORTFOLIO TRIALS IN THE CTRP. >> ANYTHING SUPPORTED BY NCI, ALL TRIALS ONGOING AT NCI DESIGNATED CANCER CENTERS INCLUDING INDUSTRY TRIALS AND INCLUDES TRIALS FUNDED BY OTHER INSTITUTES TAKING PLACE IN NCI-DESIGNATED CANCER CENTERS. >> WE'RE ALSO BROADENING COVERAGE OF V.A. TRIALS. >> NON-OVERLAP WOULD BE IN FRANCE. >> THERE'S A 10% DIFFERENCE BETWEEN CTRP AND clinicaltrials.gov FOR U.S. INTERVENTIONAL CLINICAL TRIALS. THE MAJORITY OF THOSE ARE THE TRIALS THAT ARE GOING ON OF NETWORKS OF PHYSICIAN GROUPS THAT ARE OUTSIDE NCI-DESIGNATED CANCER CENTERS OR TRIALS LET'S SAY FOR MOST SURGERY, FOR NON-SMALL CELL -- TALKING ABOUT THE WORD, HUGE NUMBER OF TRIALS, MANY, EUROPE, INDIA, ASIA, NOT IN CTRP. >> I MISSPOKE. I WANT DAVID TO TALK. DAVID ARONS IS CHAIR OF -- (INAUDIBLE) SAY A FEW WORDS. >> SURE. THANKS FOR BRINGING THIS FORWARD. EXCUSE ME WHILE I COUGH. WE HEARD THIS PRESENTATION A COUPLE WEEKS AGO WITH THE NATIONAL COUNCIL OF RESEARCH ADVOCATES, THE OTHER FEDERAL ADVISORY GROUP, RESEARCH ADVOCATES, PATIENT ADVOCACY ORGANIZATIONS, RESEARCH ADVOCATES. AND SEVERAL THEMES CAME OUT OF IT THAT THEY ASKED WE REPORT BACK TO CTAC, WE SHARE WITH YOU TODAY, FIRST THAT NCI EFFORTS TO IMPROVE CLINICAL TRIAL SEARCHING WAS PRESENTED, WE TALKED ABOUT THAT. FINDING THE RIGHT TRIAL FOR THE RIGHT PERSON AT THE RIGHT TIME, ESSENCE OF PRECISION MEDICINE IS ABSOLUTELY CRITICAL. WE SEE THIS AS CONSISTENT AND ALSO TERRIBLY IMPORTANT FOR THE NCI EFFORTS TO FURTHER PRECISION MEDICINE. AS WELL AS TO CLEAR UP THE CONFUSION AROUND clinicaltrials.gov AND PROVIDE A GREAT PRODUCT FOR PATIENTS AND PROVIDERS. A LOT OF PASSION AND INTEREST IN THIS TOPIC AND ADVOCACY COMMUNITY. I THINK SOME OF US CREATED OUR OWN SEARCH ENGINES, WE'VE DONE THAT IN BRAIN TUMORS TO WORK AROUND clinicaltrials.gov BUT MOST GROUPS CAN'T DO THAT. WE DID IT. WE FOUND A COMPUTER PROGRAMMER WHO IS A VOLUNTEER, WHO CAN DO IT FOR FREE. BUT SO THIS IS REALLY IMPORTANT WORK TO PATIENTS, AS YOU KNOW. DEVELOPING STRUCTURED INFORMATION ABOUT CLINICAL TRIALS THAT'S INTEROPERABLE WITH OTHER SYSTEMS WILL SUPPORT THE ENTIRE COMMUNITY, THE INTEROPERABILITY ISSUE THIS GROUP IS PAYING ATTENTION TO, SO IMPORTANT, HELPING PATIENTS AND PHYSICIANS. AND THEN INTEGRATION OF PRESENTATION, INTEGRATING PRESENTATION OF CLINICAL TRIALS INTO THE WORK FLOW COULD LEAD TO INCREASED CLINICAL TRIAL PARTICIPATION AND POTENTIALLY ADDRESS DISPARITIES IN THE PATIENTS WHO ENROLL IN CLINICAL TRIALS. OBVIOUSLY WE'VE TALKED ABOUT REDUCING HEALTH DISPARITIES. WE'VE TALKED ABOUT IN DIFFERENT MEETINGS THAT HELPING PATIENTS FIND THE RIGHT TRIAL FOR THEM IS OFTEN A NON-REIMBURSABLE EVENT. BUT DOCTORS, PROVIDERS, NURSES, EVERYBODY WANTS TO DO IT BECAUSE THEY KNOW IT'S THE RIGHT THING TO DO. EVEN IF IT'S NOT SOMETHING THAT'S A REIMBURSABLE 45 MINUTES. AND THIS CAN HELP CREATE EFFICIENCIES THAT WILL HOPEFULLY INCENT NAVIGATION AND EDUCATION AROUND CLINICAL TRIALS. THE NCRA OFFERED THREE PIECES OF ADVICE TO THE GROUP GOING FORWARD. THINKING ABOUT THE ULTIMATE END PRODUCT, KNOWING THERE'S A PROCESS IN PLACE TO GET THERE. BUT THREE THINGS THAT CAME OUT, ONE IS HOPEFULLY AT THE END OF THE DAY THIS WILL BE HELPFUL CROSS CULTURALLY WITH LANGUAGE DIFFERENCE ALSO IN MIND. THE UNITED STATES ALONE IS SO DIVERSE THAT HOW DO YOU MAKE THIS PROCESS AND THEN THE PRODUCT THAT COMES OUT REFLECTIVE OF THAT DIVERSITY. HELPFUL ACROSS CANCERS. MORE AND MORE WE'RE NOT TALKING ABOUT HISTOLOGY, ALTHOUGH THE PATIENT COMMUNITY BUCKETS ITSELF MOSTLY BY HISTOLOGY, CANCER TRIALS IN THE WORLD OF PRECISION MEDICINE ARE BEYOND HISTOLOGY AND SO HOW CAN SEARCH TERMS, STRUCTURE, INTEROPERABILITY, EVERYTHING HELP PATIENTS AND PHYSICIANS AND PROVIDERS, NURSES, EVERYONE WORKING ON THIS TO LOOK AT CANCER, LOOK AT TRIALS THAT MAY NOT NEATLY FIT INTO THE HISTOLOGICAL BUCKET BUT MAY BE SOMETHING THAT'S FOCUSED ON MOLECULAR PARAMETERS THAT COULD OPEN UP NEW POSSIBILITIES FOR PATIENTS. THIRDLY, EFFORTS TO HOPEFULLY -- HOPEFULLY THIS END PRODUCT WILL ENABLE BETTER TEACHING OF PROVIDERS AND HELP PROVIDERS IN TURN HELP PATIENTS. SO WE WANT PATIENTS TO UNDERSTAND THEY ARE GOING IN TO SEE THEIR CARE PROVIDERS, IF THEIR CARE PROVIDERS ARE UNCOMFORTABLE WITH IT OR SEE IT AS A TOOL THEY WON'T USE THAT MAY NOT BE AS USEFUL, SO WE'RE TRYING TO GET THE OPPOSITE OF THAT, SOMETHING WHERE IT'S VERY EASY TO INTEGRATE INTO PRACTICE. FINALLY, THE NCRA STRONGLY RECOMMENDED TO THE NCI THAT IT CONTINUES TO SUPPORT THIS COLLABORATIVE. THE GROUP OF STAFF AT NCI AND VOLUNTEERS WORKING TO MAKE THIS A GREAT PROJECT GOING FORWARD. SO COMMEND YOUR WORK. THANK YOU, DOCTOR. >> THANK YOU. >> I TOO WANT TO COMMEND YOUR WORK. I THINK LIKE MANY PROJECTS THE NCI HAS TAKEN ON TO TRY TO STANDARDIZE LANGUAGE WE USE IN TRIALS HAS POTENTIAL FOR A SERIES OF IMPACTS, MANY OF WHICH YOU'VE ARTICULATED EXTREMELY WELL. I HAVE A COUPLE QUESTIONS IF I MAY. ONE WAS THE IDEA OF STARTING WITH TRIALS WITHIN THE ECTN, BECAUSE THAT'S NOT NECESSARILY WHERE MY THOUGHT WENT IMMEDIATELY. >> I THINK IT'S A MULTI-PRONGED APPROACH, SO WE HAD AN OPPORTUNITY BECAUSE WE ARE WORKING ON AUTHORING ECTN PROTOCOLS TO SEE FIT MIGHT BE PRACTICAL TO DO IT AT THAT TIME. BUT I WOULD AGREE THAT IT NEEDS TO BE A MULTI-FACTORIAL APPROACH SO I THINK THE SECOND IS HOW DO YOU TAKE PROTOCOLS THAT ARE ALREADY WRITTEN AND STRUCTURE THEM AND CAN YOU FIND CONSISTENT WAYS OF EXPRESSING RECURRENT THAT THE DISEASE IS RECURRENT, OR MAYBE THERE ARE TWO OR THREE OTHER FACTORS THAT MIGHT ACTUALLY HELP YOU REFINE THE SEARCH STRATEGY. SO THE CHOICE OF ETCTN WAS MORE OF CONVENIENCE THAN THIS IS THE WELL-THOUGHT-OUT FIRST GROUP OF PROTOCOLS TO START WITH, THAT MIGHT BE A WAY TO DESCRIBE IT. >> YES, I CAN UNDERSTAND YOUR THINKING ALONG THAT LINE FOR THE REASONS YOU'VE OUTLINED. MY SUGGESTION WOULD BE TO START WITHIN A DISEASE AREA BECAUSE YOU WILL BE ABLE TO IDENTIFY KEY AREAS AND PRINCIPLES TO ADDRESS THOSE AREAS THAT CAN BE APPLIED TO THE NEXT DISEASE AREA AND NEXT DISEASE AREA. >> WE'VE THOUGHT ABOUT THAT. WE HAVE A LOT OF ENTHUSIASTIC PEOPLE, SO SOME OF MY COLLEAGUES SAID LET'S JUST TAKE LUNG CANCER TRIALS AND SEE IF WE CAN DO IT. SO I THINK WHAT WE'RE HOPING TO DO IS DO A COUPLE SMALL PILOTS AS WE MOVE THROUGH THE NEXT THREE TO SIX MONTHS, MAYBE ETCTN PROTOCOL AUTHORING IF THAT WORKS, MAYBE TRY TO SEE LUNG CANCER, DID THAT APPROACH WORK, A THIRD THING WE'VE BEEN WORKING ON TO SUPPORT THE TOP HEALTH PROJECT IS TRANSLATING SOME OF THE NCTN TRIALS SO ELIGIBILITY CRITERIA AND SEE IF WE COULD MATCH THOSE TRIALS TO POTENTIAL PARTICIPANTS AND SEE HOW THAT WORKS OUT. WE HAVE THREE OR FOUR TINY PILOTS THAT WE'RE MOVING FORWARD IN PARALLEL. >> MY SECOND QUESTION, WHY ISN'T THE NATIONAL LIBRARY OF MEDICINE INVOLVED SINCE THEY MANAGED THE clinicaltrials.gov? >> WE TALKED TO THEM ALL THE TIME. AND WE ARE LOOKING FROM A CANCER-SPECIFIC PART OF THE WORLD, NOT A BROAD DISEASE PART OF THE WORLD. AS WE MOVE FORWARD AND HAVE MEETINGS WITH STAKEHOLDERS OUTSIDE OUR LITTLE NCI WORLD WE CERTAINLY WILL WANT TO TALK TO THEM BECAUSE WE KNOW THEY HAVE BEEN WORKING ON THE SAME PROBLEM FOR A LONG TIME AND WE WILL BE WORKING WITH THEM, THAT'S THE BEST WAY OF DESCRIBING IT. >> OKAY. >> AGAIN, I COMMEND YOU. I THINK THERE WOULD BE HUGE EFFICIENCIES TO BE GAINED IF WE COULD JUST REMOVE SOME OF THE VARIATION THAT WE HAVE CREATED. >> RIGHT. >> WHICH HAS NO GOOD REASON. THERE ARE PROTOCOLS OBVIOUSLY THAT HAVE VARIATION FOR GOOD REASON BUT MOST OF IT IS AS YOU ILLUSTRATED, IT'S TEXT, VERBIAGE, MEANS THE SAME THING AND YET WE COULD MAKE IT A LOT SIMPLER. >> RIGHT. I'D LIKE TO GO BACK TO THE COMMENT ABOUT NLM. THEY HAVE STRUCTURED -- THEY EVER REALLY STRUGGLED WITH THE SAME PROBLEM BECAUSE THEY WANT TO BE ABLE TO GET PATIENTS TO TRIALS. SO I THINK WE'RE MOVING A LITTLE BIT IN THE CANCER SPACE, WE'LL REGROUP AND SAY THIS IS WHAT WE DID, WHAT DO YOU THINK. BUT WE'RE NOT QUITE ON FAST DIAL BUT WE'RE ON FAST COMPUTER CONNECTION. >> OKAY. SHEILA AND HOWARD AND WE'RE -- >> ONE COMMENT. WITH JANET, STARTING WITH THE ETCTN THIS IS AT THE PROTOCOL AUTHORING POINT, RIGHT? BECAUSE RIGHT NOW NCI IS ACTUALLY OFF THE PROTOCOLS. WE HAVE THE POTENTIAL TO ACTUALLY MAKE SURE THEY ARE WRITTEN THE SAME WAY -- AUTHORING THE PROTOCOLS. THE NCTN GROUPS HAVE TO AGREE TO AUTHOR IN THE STANDARD WAY. >> YEAH, I WITH UNDERSTAND THAT, THE WHOLE OF THE PROTOCOL, THAT MAKES SENSE. IF YOU WANT TO TACKLE A THING THAT WOULD HAVE HUGE IMMEDIATE IMPACT, STANDARDIZE ELIGIBILITY CRITERIA, FOLLOWS NATURALLY WITH THE MOVE TOWARDS SIMPLIIED ELIGIBILITY CRITERIA. >> JUST GOING TO SUGGEST THE THOUGHT OF HAVING A NICE CONVERSATION, DISCUSSION WITH THE GROUP THAT'S WORKING ON THE MODERNIZATION OF ICHE 8, THAT'S GOING TO BE PUBLICLY RELEASED, THE ICH GROUP, THINK IN THE FIRST QUARTER OF 2019 SO COINCIDES. TO GIVE AN EXAMPLE YOUR SLIDES 4, 8 AND 10 DESCRIBE THE WORD "PATIENT," WHEREAS THE TERM, I THINK, THAT'S GOING TO BE IN THE GUIDANCE IS GOING TO USE "SUBJECT," ESPECIALLY TALKING ABOUT LIKE PATIENTS THAT DON'T HAVE CANCER BUT PREVENTION TRIALS OR, YOU KNOW, DIAGNOSTIC TRIALS, WHATEVER. HEALTHY VOLUNTEER TRIALS WILL BE CALLED "SUBJECTS." THERE'S MULTIPLE TERMS LIKE THAT AS THEY MAY BE USED AND SEARCHED BY PEOPLE THAT COULD DIFFER THAN WHAT -- HOW YOU SELECTED. IT MAY BE USEFUL TO HAVE A GOOD HARD LOOK AT THAT DRAFT GUIDANCE. I THINK IT'S IN THE EARLY STAGES. SOMEBODY LIKE LISA LAVAGNE OR FERGUS SWEENEY CAN PROVIDE THAT. MARK MILANSON FROM THE FDA IS ON THAT COMMITTEE. >> OKAY. THANK YOU. >> GREAT. THANK YOU, GISELLE. SO DAVID, JEFF, JOIN JIM AND I UP FRONT. WE HAVE A LITTLE PRESENTATION. >> THIS IS ONE OF MY FAVORITE PARTS OF THE MEETING. WE GET TO THANK SOMEONE WHO PARTICIPATED SO ACTIVELY IN CTAC AND ALSO MANY WORKING GROUPS. DAVID ARONS HAS SPENT YEARS COMING TO THESE MEETINGS. AND HAS REALLY PLAYED A CRITICAL ROLE, PROVIDING INPUT, NOT ONLY FROM HIS PERSPECTIVE AS CHAIR OF THE ADEQUACY COUNCIL BUT REPRESENTING THE BRAIN TUMOR COMMUNITY IN THIS ENTIRE CONTEXT. WE'RE REALLY HAPPY. WE'RE NOT HAPPY TO SEE YOU LEAVE BUT WE'RE HAPPY FOR ALL THE EFFORT YOU PUT IN, AND THE PLEASURE IT'S BEEN TO WORK WITH YOU. THANK YOU SO MUCH. [APPLAUSE] >> USUALLY WE STAND HERE FOR SOMEBODY TO TAKE A PICTURE BUT THERE'S NO CAMERA. >> WE'RE AHEAD OF SCHEDULE. THE PHOTOGRAPHER HAS NOT ARRIVED. >> THANK YOU. THANK YOU SO MUCH. >> I'M NOT WORTHY TO DO THIS BUT I GOT ASSIGNED TO DO THIS. AND I -- I'M HERE BASICALLY TO HONOR JEFF ABRAMS FOR HIS MANY YEARS OF WORK HERE AT THE NCI. HE CAME HERE IN THE NCI 1993, BECAME A CTEP ASSOCIATE DIRECTOR SINCE 2007, HE'S PRESENTED HERE I THINK 14 DIFFERNT TIMES. HE WAS -- AT ASCO THE MOST IMPORTANT STUDY HAD JEFF'S FINGERPRINTS ON IT. ONE OF THE MOST IMPORTANT TRIALS AROUND BECAUSE, AGAIN, GOING BACK TO THIS GOOD TO GREAT, IT DECIDED WHAT WE SHOULDN'T BE DOING, AND THAT WILL IMPROVE THE CARE OF WHAT WE DO HERE. HE HELPED JIM CONSOLIDATE THE CLINICAL TRIALS GROUP, CONSOLIDATE TEN MASSIVE GROUPS INTO FIVE. HE'S BEEN -- HE PIONEERED THE CANCER TRIAL SUPPORT UNIT, AND HE'S BEEN A TERRIFIC GUY. NANCY DAVIDSON WOULD BE HERE PRESENTING BECAUSE YOU'VE KNOWN NANCY ALMOST YOUR PROFESSIONAL LIFE. YOU WERE AT MARYLAND WHEN SHE WAS AT JOHNS HOPKINS, AND SHE'S KNOWN YOU FOREVER. SHE WROTE SOME WORDS. I'LL GIVE IT TO YOU. SHE CONCLUDED THIS BY SAYING, THIS IS NANCY'S WORDS, I SPENT COUNTLESS HOURS WITH JEFF OVER THESE YEARS AND THANK HIM FOR HIS UNWAVERING COMMITMENT, WISDOM AND PASSION. INVESTIGATORS ACROSS THE UNITED STATES HAVE BEEN SUPPORTED BY HIS WORK. MOST IMPORTANTLY, HIS WORK AT THE NCI HAS TOUCHED THE LIVES OF SO MANY PATIENTS IN A PALPABLE WAY. HE'S TRULY BEEN A GOVERNMENT SERVANT FOR THE PEOPLE AND WE'RE BETTER FOR HIS SERVICE. I'D LIKE TO HAVE JEFF COME UP ON BEHALF OF THE CTAC COMMITTEE. WE FIGURED YOU DIDN'T WANT A PLAQUE BECAUSE YOU'RE RETIRING, YOUR WIFE WOULD NOT BE IMPRESSED WITH A PLAQUE IN YOUR OFFICE AT HOME. [LAUGHTER] SO WE CAME UP WITH THIS. WE ASKED THE MEMBERS OF THE GROUP TO COME UP WITH THE ONE WORD THAT THEY WOULD USE TO DESCRIBE YOU. AND THEN THROUGH THAT, BECAUSE THERE WERE SO MANY DIFFERENT WORDS WE CAME UP WITH THIS, PRACTICAL, INSPIRING, ON THE BACK PRESENTED BY CTAC 2018. MORE IMPORTANTLY, THE NEXT FIVE MINUTES, YOU GET THIS ALSO, ANOTHER LITTLE GIFT, WHICH IS ACTUALLY -- YOU DON'T HAVE TO WEAR THIS. YOU CAN DRINK FROM THIS. IT HAS THE SAME WORDS ON HERE, ON THE BACK IS ALL THE MEMBERS OF CTAC WHO WILL MISS YOU TREMENDOUSLY. THANK YOU FOR YOUR SERVICE. [APPLAUSE] >> WE AREN'T DONE YET. >> NOT DONE. >> JEFF, ON BEHALF OF THE NCTN GROUP CHAIRS, ON BEHALF OF JANET, MONICA, PETER, PETER, CHUCK, NORMAN, ROBERT AND MITCH, AND BERNIE FISCHER AS WELL, WE WANT TO ALL THANK YOU FOR ALL YOU'VE DONE FOR THE GROUPS, AND THIS IS ON BEHALF OF THAT GROUP. [APPLAUSE] >> A FEW WORDS. IT'S HARD TO SAY A FEW WORDS AFTER 25 YEARS, BUT IT'S ALWAYS BEEN A GREAT PLEASURE TO WORK AT THE NCI AND TO PARTICIPATE WITH ALL OF YOU IN THIS MISSION TO PREVENT AND CURE CANCER. IF WE CAN'T DO THAT AT LEAST DEAL WITH IT AND MANAGE IT BETTER. AND THE PEOPLE WHO WORK HERE I THINK ARE INSPIRED BY ALL THAT DO YOU BACK NUT OF -- BACK OUT IN THE EXTRAMURAL COMMUNITY. IT'S A UNIQUE INSTITUTION BECAUSE OF THAT TEAM WORK. I THINK IT'S REALLY A SHINING EXAMPLE HOW PUBLICLY FUNDED RESEARCH CAN IMPROVE THE LIVES OF PEOPLE WITH THESE TERRIBLE ILLNESSES. AND SO FOR ME IT'S BEEN A GREAT PRIVILEGE, REALLY, TO WORK WITH YOU AND SHARE MANY GREAT MOMENTS, SEEING CLINICAL TRIAL RESULTS COME OUT AT IMPORTANT MEETINGS AND ENJOY THE CAMARADERIE OF WORKING IN THIS IMPORTANT MISSION. THANK YOU ALL VERY MUCH. [APPLAUSE] >> JEFF IS RETIRING. WE FOUND OUT, THERE ARE INFINITE NUMBERS OF Rs AND Ps AND OTHER KINDS OF GRANT MECHANISMS. WE FOUND A SPECIAL VOLUNTEER MECHANISM THAT HE IS GOING TO BE BESTOWED WITH. THIS IS REALLY SPECIAL VOLUNTEER BECAUSE IT MEANS THAT AT ANY TIME WE CAN BRING HIM BACK TO WORK AT CTEP, WHEN WE REALLY NEED A SENIOR LEADER. HE'S GOING TO FIND OUT THOUGH, IN ABOUT A MONTH OR SO, WHEN THIS HAPPENS. OKAY. WE'RE GETTING TOWARD THE END OF OUR MEETING. WE'RE GOING TO MOVE TO A VERY IMPORTANT TOPIC, SOMETHING YOU ALL INSPIRED US TO MOVE FORWARD WITH. I'M GOING TO INTRODUCE JANET EARY, OUR NEW CHIEF OF CANCER IMAGING PROGRAM, TO BASICALLY SET THE STAGE FOR FURTHER DISCUSSIONS OF OUR QUANTITATEIVE IMAGING NETWORK. JANET? >> THANK YOU. THANK YOU FOR THE INTRODUCTION. PLEASURE TO BE BACK TO CHAT WITH YOU. THE PROGRAM DIRECTOR, BOB NORDSTROM, FOR THE QUANTITATIVE IMAGING NETWORK PRESENTED AN OVERVIEW, THE QUANTITATIVE IMAGING NETWORK WITH BASIC CONCEPTS ABOUT WHAT QUANTITATIVE IMAGING TOOLS ARE AND HOW THE NETWORK FUNCTIONS. WE'RE BACK TODAY TO GIVE YOU A BRIEF PRESENTATION ABOUT A PROPOSAL FOR WORKING GROUP FOR QUANTITATIVE IMAGING TOOL TRANSLATION. THAT'S WHAT I WANT TO DESCRIBE TO YOU TODAY. SO JUST BY WAY OF REVIEW, IMAGING, WHICH YOU'RE ALL AWARE OF, HAS A LOT OF INFORMATION THAT'S USEFUL IN CLINICAL TRIALS. IN THE CANCER IMAGING PROGRAM, MYSELF INCLUDED, WE CONSIDER IMAGING TO BE GRAPHIC REPRESENTATIONS OF DISEASES OF BIOLOGICAL PROCESS, ALMOST ANY LEVEL. AND THAT BEING THE CASE, YOUR CONSIDERATION OF IMAGING IS PARTICULARLY TIMELY. SO WHAT QUANTITATIVE IMAGING IS, EXTRACTION OF QUANTITATIVE MEASURABLE DATA FROM MEASURABLE IMAGES OF THE TIMES IN THE PREVIOUS SLIDE FOR ASSESSMENT OF STATUS OR CHANGE IN DISEASE. MANY WILL BE ABLE TO BE USED AS BIOMARKERS IN SUPPORT OF CLINICAL DECISION MAKING. BUT MORE IMPORTANTLY, WE NEED TO THINK ABOUT IT AS DATA IMAGING, QUANTITATIVE IMAGING DATA FROM DIFFERENT MODALITIES AS INPUT AS PART OF THE INTERACTION BETWEEN DATA ANALYTICS IMAGING AND INFORMATICS, THAT'S A THEME WE'VE ALL BEEN INVOLVED WITH IN PURSUING AT THE NCI. THE QUANTITATIVE IMAGING NETWORK ROAD MAP STARTED WITH THROUGHOUT ITS COURSE IN THE NETWORK AND THAT'S EVALUATION OF HARDWARE PERFORMANCE, DEVELOPMENT OF TOOLS, HARMONIZATION, AND USE OF THOSE. AND A LOT OF TECHNICAL AREAS IN REDUCING VARIANTS IN DATA COLLECTION, PARTICULARLY ACTIVE IN CREATING ROBUST ALGORITHMS TO EXTRACT INFORMATION FROM DIFFERENT IMAGES. THEY ARE IN THE PROCESS NOW THAT THE NETWORK INVESTIGATORS HAVE MATURED IN THEIR WORK INTO TESTING PHASES AND VALIDATION OF THESE TOOLS IN VARIOUS DIFFERENT CLINICAL SCENARIOS AND THEY HAVE BEEN INTRODUCING NEW ALGORITHMS TRYING TO FIGURE OUT WAYS TO PUT THEM INTO CLINICAL WORKFLOW WHERE THEY COULD BE ADAPT AND USED. THEY HAVE CREATED A NUMBER OF INTERACTIONS. SO WHERE ARE WE WITH ALL OF THESE? THE WAY THAT THE TOOLS THAT THE NETWORK HAS BEEN DEVELOPING HAVE BEEN BENCHMARKED IN VARIOUS WAYS, I DREW A RED LINE THERE BETWEEN ITEMS 3 AND 4. HERE IS WHERE WE ARE NOW, 67 TOOLS, AND ABOUT A DOZEN READY TO BE TEED UP INTO CLINICAL TRIAL BENCH MARKING WITH THE IDEA TOWARD EVENTUAL CLINICAL USE, NOT JUST RESEARCH TOOL USE. SO, WHAT OUR QUESTION FOR CTAC IS, WHAT MORE CAN THE QUANTITATIVE IMAGING NETWORK DO TO INTERACT TO DISTRIBUTE AND TEST QUANTITATIVE IMAGING TOOLS, THE NETWORK HAS BEEN ACTIVELY PUBLISHING AND PROMOTING TOOLS, AT ALL OPPORTUNITIES, MEETINGS, AND DIFFERENT CONVERSATIONS WITH FOLKS IN THE CLINICAL TRIALS WORLD. WE'VE BEEN TRYING TO THINK OF DIFFERENT WAYS TO MOTIVATE TEAMS TO MOVE INTO TEST VALIDATION PHASES, AND OUT OF THE CONSTANT DEVELOPMENT PHASE. AND WE'RE INCREASING INDUSTRY AND FDA PARTICIPATION IN THE NETWORK. SO WE'RE ASKING CTAC FOR ADDITIONAL IDEAS. SPECIFICALLY, THE QUESTION FOR ALL OF YOU IN CTAC IS HOW WE CAN FACILITATE TESTING AND IMAGING TOOL IMPLEMENTATION IN CLINICAL TRIALS FOR EVENTUAL USE. SO, WE PROPOSE THE CREATION OF A CTAC-BASED GROUP TO ADVISE ON STRATEGIES FOR INTEGRATION OF NETWORK TOOLS INTO CLINICAL TRIALS. TO HELP US ASSESS THE CURRENT STATUS OF USE OF TOOLS, QUANTITATIVE IMAGING TOOLS IN CLINICAL TRIALS AND PRACTICE AND HELP IDENTIFY BARRIERS AND STRATEGIC APPROACHES FOR ENHANCING THE TOOL TESTING AND INTEGRATION IN CLINICAL TRIALS. WE'D LIKE TO START WITH A SELECTED SUBGROUP OF YOU WITH AD HOC EXPERTS AS NEEDED FOR ADDITIONAL MEETINGS. WE DON'T ENVISION THIS GROUP WILL BE ACTIVE MORE THAN A YEAR OR SO, REALLY SHOULD BE A SHORT-TERM GROUP TO PROVIDE RECOMMENDATIONS AND PROVIDE US WITH SOME ADVICE. THAT WAS PRETTY MUCH ALL I HAD TO SAY TO REMIND YOU WHAT THE ISSUE WAS ON THE TABLE AND THE BACKGROUND FOR OUR REQUEST. >> ALL RIGHT. WHAT I WILL ACTUALLY -- TO MOVE THINGS ALONG WILL ENTERTAIN A MOTION AND WE'LL HAVE DISCUSSION. ANYBODY WANT TO MAKE THIS MOTION FROM THE COMMITTEE? >> THANK YOU. >> DAVID DOES. ANY SECONDS? ALL RIGHT. LET'S HAVE SOME DISCUSSION ON THIS. BASICALLY I REALLY APPRECIATE YOU DOING THIS AND PRESENTING THIS TO THE GROUP, ANY DISCUSSION ON THIS IN TERMS OF WHETHER OR NOT WE SHOULD FORGE AHEAD OR COMMENTS? YEAH, DAVID? >> VERY BRIEF, I'M AN ACKNOWLEDGED DOUBLE AGENT AS ACTIVE MEMBER OF QIN. I WAS IMPRESSED HOW EVERYBODY WAS, THAT WAS GREAT. WORKING IN A COUPLE SUBGROUP COMMITTEE, QIN IS REACHING OUT, THERE'S A LOT TO BE GAINED BY HAVING A FORMAL WORKING GROUP AS IT BRINGS PEOPLE NOT ONLY ENGAGED IN NCTN, CANCER CENTERS, A VARIETY OF ORGANIZATIONS, NCORP, A GREAT IDEA WITH MY ADMITTED CONFLICT OF INTEREST, MAKING THAT RECOMMENDATION. >> GREAT. ANY OTHER THOUGHTS? YES, WALLY? >> SO IF I LOOK AT WHAT THE PROPOSED FUNCTIONS OF THE GROUP ARE, IT'S REALLY TO ENHANCE INTEGRATION. SOMETIMES WHEN YOU GET A SUBCOMMITTEE OF A SUBCOMMITTEE OR WHATEVER WE CALL, IT'S TO ASSESS SUCCESS OR LACK THEREOF OF AN INITIATIVE. ASSUMED IN THIS IS QIN IS WORKING, AND WE WANT TO MAKE IT BETTER. THERE MAY BE MORE FUNDAMENTAL FUNCTIONS FOR THIS AND THAT IS IS QIN SET UP PROPERLY, NOT IS THE ENDPOINT -- ARE WE ASSUMING QIN IS A BLACK BOX, DOING RIGHT AND ALL WE HAVE TO ASSUME IS YOU CLINICAL TRIALISTS NEED TO INTEGRATE OUR TOOLS BETTER. I PERSONALLY THINK THERE'S A MORE FUNDAMENTAL QUESTION, IS THIS THE RIGHT MODEL. AND I'M NOT CHALLENGING IT BUT I'M JUST SAYING IT'S AN AWFULLY SMALL FOCUS OF A WORKING GROUP OUT OF THIS COMMITTEE IS MY VIEW. >> ADDED TO THE CHARGE I THINK. ANY OTHER? IT'S UP TO YOU THOUGH. ARE YOU AWAKE? >> YEAH. >> OKAY. [LAUGHTER] >> IT'S USUALLY NAP TIME. >> TITILLATING MEETING. LEGISLATIVE UPDATE IS COMING UP. WE'LL FIND OUT WHO WON. >> WE'RE WAITING TO FIND OUT WHO WON YESTERDAY. NO, THINK, WALLY, IT'S A GREAT ADDITION TO THE CHARGE AND WE SHOULD ADD THAT AND MOVE FORWARD IF YOU AGREE. >> YEAH. MAYBE I MISSED IT BUT I'M AWARE THAT THE BIOMARKERS CONSORTIUM HAS A SUBTEAM WORKING ON RADIOMIX AND QUANTITATIVE IMAGING AND VOLUMETRIC IMAGING. I IMAGINE THE PROGRESS THEY ARE MAKING AND DATA THEY COULD BRING WOULD BE PART OF THIS. >> ARE YOU TALKING ABOUT THE NIH? >> YEAH. WELL, THERE'S NO REASON THE WORKING GROUP COULDN'T GET INPUT FROM THAT GROUP, CERTAINLY. >> ALL RIGHT. I WANT TO CALL THE QUESTION THEN, ALL THOSE IN FAVOR OF THIS WORKING GROUP ESTABLISHING, SAY AYE. >> AYE. >> OPPOSED? HEARING NONE, IT IS PASSED. THANK YOU. ALL RIGHT. SO WE'RE NOW -- LAST NIGHT I WAS BUSY WATCHING TV. IT WAS SO EXCITING. I SAID, WHY AM I DOING THIS? I WOKE UP AT TWO IN THE MORNING. NO, I DON'T NEED TO DO THAT BECAUSE WE'RE GOING TO HAVE THIS LEGISLATIVE UPDATE. HOLLY IS GOING TO TELL US EVERYTHING THAT HAPPENED. WE PUT HER AT THE END OF THE DAY BECAUSE YOU WOULD HAVE UPDATES. >> I'VE BEEN UPDATING AS WELL. >> TERRIFIC. HOLLY GIBBONS, DEPUTY DIRECTOR, OFFICE OF GOVERNMENT RELATIONS, LOOK FORWARD TO HEARING YOUR PRESENTATION. >> THANKS FOR THE OPPORTUNITY TO JOIN YOU THIS AFTERNOON. I'M HOLLY GIBBONS, NCI OFFICE OF GOVERNMENT AND CONGRESSIONAL RELATIONS. YOU HEAR FROM MY COLLEAGUE WHO IS DISAPPOINTED TO MISS THE MEETING BUT I'M GLAD TO REPRESENT OUR TEAM, ESPECIALLY ON SUCH AN INTERESTING DAY AFTER THE MIDTERM ELECTIONS. THAT'S WHERE I'LL START SINCE I'M SURE THAT'S THE MOST TIMELY AND WHAT EVERYONE IS MOST INTERESTED IN HEARING ABOUT. I'LL ALSO GO BACK AND TOUCH ON A FEW THINGS DR. SHARPLESS MENTIONED THIS MORNING WITH AN APPROPRIATIONS RECAP, RECENT HEARINGS, BRIEFINGS AND VISITS AS WELL AS A COUPLE UPDATES ON LEGISLATIVE IMPLEMENTATION. MIDTERMS, A BASELINE, THIS IS A GRAPHIC FROM THE NATIONAL JOURNAL, SHOWING THE CURRENT 115th CONGRESS, WE HAVE A MAJORITY OF 235 235 REPUBLICANS IN THE HOUSE, 51 IN THE SENATE. EVERYONE WAS INTERESTED TO SEE, THE DEMOCRATS DID TAKE CONTROL OF THE HOUSE, REPUBLICANS DID MAINTAIN MAJORITY IN THE SENATE. I'LL GO INTO MORE DETAIL THERE. THERE ARE A FEW THINGS WE ARE STILL WAITING TO FIND OUT. ALSO I WANT TO TALK ABOUT WHAT IT MEANS FOR NIH AND NCI AND WHAT WE'LL BE WATCHING FOR HEADING INTO THE NEW CONGRESS. SO THIS IS JUST A SCREEN SHOT OF THE AP'S RESULTS, 1:30, AS WE WERE SITTING THERE. YOU'LL SEE IN THE HOUSE DEMOCRATS RIGHT NOW HAVE 220-SEAT MAJORITY, REPUBLICANS HAVE 196 SEATS, THERE ARE STILL SEVERAL SEATS UP IN THE AIR THAT HAVEN'T BEEN CALLED. OF THOSE, ABOUT EIGHT OF THEM BASED ON CURRENT VOTE COUNTS LEANING TOWARD THE DEMOCRATS, REST TOWARDS REPUBLICANS, WE MAY HAVE SOME SOMEWHERE IN THE RANGE OF 228 SEATS FOR REPUBLICANS, 206 FOR THE DEMOCRATS -- 206 FOR THE REPUBLICANS. BEFORE I CAME TO THE MEETING I WAS TAKING A CLOSER LOOK AT CTAC MEMBERSHIP. YOU ARE A VERY INTERESTING MICROCOSM OF THE MIDTERM ELECTION. WE HAD A FEW COMPETITIVE SENATE SEATS REPRESENTED ON CTAC INCLUDING TWO THAT CHANGED HANDS, MISSOURI AND INDIANA. WE HAD A COMPETITIVE HOUSE RACE IN MINNESOTA JUST CALLED FOR THE REPUBLICAN IN MINNESOTA'S FIRST DISTRICT. COMPETITIVE GOVERNOR'S RACES, ONE WE DON'T KNOW THE OUTCOME OF. WE'RE STILL WAITING TO FIGURE OUT, ON THE SENATE SIDE REPUBLICANS HOLDING THEIR 51 SEAT MAJORITY EXPECTED TO GROW. WE HAVE RUNOFF ELECTION IN MISSISSIPPI, FOUR CANDIDATES, NONE OF THOSE REACHED 50%, RUNOFF THERE, REPUBLICAN INCUMBENT IS EXPECTED TO WIN THERE. ALTHOUGH YOU NEVER KNOW WHAT CAN HAPPEN. WE HAVE TWO SENATE SEATS THAT ARE YET TO BE CALLED. GOING INTO THIS MORNING MONTANA STILL IN THE AIR, JUST RECENTLY CALLED FOR INCUMBENT SENATOR KESTER, ARIZONA HAS NOT BEEN CALLED, SENATOR FLAKE RETIRING, TWO MEMBERS OF THE HOUSE, McSALLY AND SINEMA RUNNING FOR THAT SEAT. IN FLORIDA A CLOSE RACE, THIS MORNING INCUMBENT SENATOR NELSON IS CALLING FOR A RECOUNT, THAT'S AGAINST CURRENT REPUBLICAN GOVERNOR TIM SCOTT IN FLORIDA. STILL A FEW QUESTIONS IN THE SENATE. THIS MAP WAS SHIFTING ALL MORNING, BOTH WILL CONTINUE TO DO SO THROUGHOUT THE WEEK AND WITH ANOTHER RECOUNT IN FLORIDA, WE'LL WAIT AND SEE WHAT HAPPENS THERE. SO IN TERMS OF WHAT THIS MEANS FOR NIH AND NCI, WE KNEW GOING INTO THE ELECTION THAT IT WOULD HAVE SHIFTS IN YOUR COMMITTEE AND SUBCOMMITTEE LEADERSHIP, AND NEW CONGRESS THE MEMBERSHIP WILL SHIFT SO WE'RE GOING TO BE PAYING CLOSE ATTENTION TO THAT LOOKING TO SEE WHO ARE THE NEW NUMBERS OF THE COMMITTEES THAT WE INTERACT WITH MOST OFTEN AND HAVE JURISDICTION OVER NIH AND NCI SO IN PARTICULAR APPROPRIATIONS SUBCOMMITTEES, AS WELL AS HELP COMMITTEE IN THE SENATE AND ENERGY AND COMMERCE COMMITTEE IN THE HOUSE. FOR THE HOUSE WE KNEW THAT CONGRESSMAN FREELING WAS RETIRING SO THERE'S A LEADERSHIP RACE THERE THAT WILL BE FOR THE RANKING MEMBER SINCE THE MAJORITY FLIPPED IN THE HOUSE OF THAT FULL COMMITTEE AND OUR SUBCOMMITTEE CHAIR TOM COLE IS IN THAT LEADERSHIP RACE. SO THAT MAY IMPACT NCI AND NIH. WE SEE SOME SHIFTS IN OUR CANCER CAUCUSES. I DON'T KNOW HOW MANY FOLKS ARE FAMILIAR WITH THAT BUT THERE ARE SEVERAL CAUCUSES IN THE HOUSE PRIMARILY, INTERESTED IN PARTICULAR AREAS OF CANCER RESEARCH SO WE HAVE OVERALL HOUSE CANCER CAUCUS, CONGRESSMAN KEVIN YODER OF KANSAS, LOST HIS RACE YESTERDAY. HE'S A CO-CHAIR OF THAT CAUCUS. CONGRESSMAN CHARLIE DENT RETIRED EARLY, ANOTHER CO-CHAIR OF THAT CAUCUS. WE'LL SEE SOME NEW LEADERSHIP OF THAT CAUCUS ON THE REPUBLICAN SIDE, LEONARD LANCE IN NEW JERSEY LOST HIS SEAT AS WELL, AND CONGRESSMAN DAVID REICHERT OF WASHINGTON STATE HAD RETIRED AS WELL AND SO THOSE ARE TWO CO-CHAIRS OF THE DEADLIEST CANCERS CAUCUS AND BOTH CO-CHAIRS OF THE LUNG CANCER CAUCUS, NOLAN AND LOBIANDO ARE RETIRING, WE'LL BE WATCHING THAT. I THINK ONE THING THAT WE'RE CONFIDENT IN BECAUSE THERE'S BEEN SUCH A STRONG TRACK RECORD OF BIPARTISAN SUPPORT, CANCER RESEARCH AND BIOMEDICAL RESEARCH REMAIN NONPARTISAN ISSUES AND WE'VE SEEN THAT TRACK RECORD OF BIPARTISAN SUPPORT OVER MANY YEARS AND THAT BRINGS ME TO MY NEXT UPDATE, WE CAN COME BACK TO THE MIDTERMS BUT I'M GOING TO MOVE TO A QUICK APPROPRIATIONS UPDATE. THIS YEAR WAS A REALLY INTERESTING YEAR. DR. SHARPLESS ALLUDED TO THE FACT THIS WAS A FIRST TIME IN A VERY LONG TIME WE RECEIVED OUR APPROPRIATION ON TIME FOR THE LABOR HHS BILL WHICH FUNDS NIH AND NCI, A STRATEGY OF COMBINING LABOR HHS BILL AND DEFENSE BILL AS WELL AS SHORT-TERM C.R. FOR SEVERAL OTHER AGENCIES, THE LAST TIME WE RECEIVED OUR FUNDS ON TIME WAS IN 1996, HEADING INTO FY 97, AND A QUICK TRIP DOWN MEMORY LANE THESE ARE A FEW THINGS THAT WERE HAPPENING IN 1996, OLYMPICS IN ATLANTA, EVERYONE WAS CARRYING THEIR FLIP PHONE, OPRAH HAD LAUNCHED HER BOOK CLUB, YOUR COLLEAGUE JIM ALLISON PUBLISHED KEY FINDINGS ON CHECKPOINT INHIBITION, NINTENDO 64 HIT THE MARKET. ONE THING THAT SETS 1996 APART FROM 2018, BACK THEN THE YANKEES WON THE WORLD SERIES, AS A RED SOX FAN, THIS YEAR IT'S DIFFERENT. YOU MAY REMEMBER M.K. TALKING ABOUT THE BILL IN PAST YEARS, CONTROVERSIAL POLICY WRITERS TACKED ON, THE DEFENSE BILL IS ONE OF THE FIRST TO MOVE. USUALLY CONSIDERED ONE OF THE MOST PASSED FUNDING BILLS. SO PAIRING THEM TOGETHER WAS AN INTERESTING MARRIAGE AND VERY STRATEGIC, ON THE PART OF THE APPROPRIATORS AND CONGRESSIONAL LEADERSHIP, AND THE PRESIDENT AS WELL, TO MOVE THIS PACKAGE THROUGH IN TIME FOR THE MIDTERM ELECTIONS. YOU'LL SEE SO MANY OF THESE HEADLINES ALLUDE TO THE FACT THE STRATEGY OF LABOR, DEFENSE, SHORT TERM CONTINUING RESOLUTION HELPED AVOID A PRE-ELECTION SHUTDOWN. WE'RE NOT SURE IF THIS IS A SIGN OF A RETURN TO REGULAR ORDER OR IF THIS IS A BLIP BECAUSE OF THE INTERESTING YEAR WE'RE HAVING. BUT WE'LL SEE NEXT YEAR WHICH IS NOT AN ELECTION YEAR WHETHER WE'RE ABLE TO SEE SOME OF OUR FUNDS ON TIME, BUT AS DR. SHARPLESS MENTIONED IT REALLY IS KIND OF A GIFT TO AGENCIES, ALLOWS THEM TO PLAN AND BE MORE EFFICIENT AND GET THINGS UNDERWAY ON SCHEDULE. SO WE'RE GRATEFUL FOR THAT THIS YEAR. AND LOOKING FORWARD TO SEEING WHAT HAPPENS NEXT YEAR. JUST WANTED TO MENTION WHEN CONGRESS RETURNS AND THEY ARE BACK IN SESSION NEXT WEEK ON NOVEMBER 13, THEY HAVE UNTIL DECEMBER 7 TO FIGURE OUT A PLAN FOR THOSE REMAINING AGENCIES. AND THOSE INCLUDE SOME AGENCIES THAT MAY BE OF INTEREST, COMMERCE, JUSTICE, SCIENCE, INCLUDING THE NATIONAL SCIENCE FOUNDATION, THAT BILL HAS NOT BEEN FUNDED YET AND AGRICULTURE FDA BILL HAS NOT BEEN FUNDED, AMONG THE REMAINING BILLS THAT NEED TO BE FUNDED AFTER DECEMBER 7th. I WANT TO RECAP HERE WHERE WE ENDED UP IN FY19 AND INCLUDE FY 18 FOR REFERENCE, YOU'LL SEE FOR 19 NCI RECEIVED $79 MILLION INCREASE TO BASE, FULL FUNDING AS AUTHORIZED BY THE CANCER MOONSHOT AND FOR NIH OVERALL THAT WAS A $2 BILLION INCREASE. FY 18 WAS SLIGHTLY DIFFERENT YEAR, BECAUSE OF THE BUDGET DEAL, OUR SUBCOMMITTEES OVERALL ALLOCATION WAS LARGER, THEY HAD ADDITIONAL FUNDS TO WORK WITH. AND NIH RECEIVED A SLIGHTLY LARGER INCREASE, SOMETHING APPROPRIATORS WARNED US WOULD NOT HAPPEN THIS YEAR. AS I MENTIONED YOU REALLY DO SEE A STRONG TRACK RECORD OF CONSISTENT SUPPORT WE'VE ENJOYED FOR THE PAST FOUR YEARS, AND REALLY APPRECIATE THAT LEADERSHIP OF OUR APPROPRIATIONS COMMITTEES AND SUBCOMMITTEES MAKING NIH AND INSTITUTES A PRIORITY. I KNOW AT YOUR LAST MEETING IN JULY M.K. HIGHLIGHTED HEARINGS WE PARTICIPATE IN, EACH SPRING THE NIH DIRECTOR IS INVITED TO TESTIFY BEFORE THE HOUSE AND SENATE APPROPRIATIONS SUBCOMMITTEES AND NCI DIRECTOR OFTEN JOINS HIM AND DR. SHARPLESS DID HAVE THE OPPORTUNITY TO JOIN DR. COLLINS LAST YEAR. THIS SUMMER, THIS WAS MORE OUT OF THE ORDINARY, OUR AUTHORIZING COMMITTEES ALSO HELD HEARINGS AND DR. SHARPLESS WAS ABLE TO JOIN DR. COLLINS AT THOSE SO HERE YOU'LL SEE A PHOTO FROM A HEARING IN FRONT OF THE HOUSE ENERGY AND COMMERCE COMMITTEE, HEALTH SUBCOMMITTEE, FOCUSING ON UPDATES ON IMPLEMENTATION OF THE 21ST CENTURY CURES ACT, DR. COLLINS AND DR. GOTTLIEB OF THE FDA PROVIDED TESTIMONY AND DR. COLLINS ASKED DR. SHARPLESS AND DR. STEPH DEVANEY OF THE "ALL OF US" PROGRAM TO FOCUS ON THE "ALL OF US" PROGRAM AND CANCER MOONSHOT PROVIDING UPDATES TO THE COMMITTEE. IN AUGUST WHEN THE SENATE IS TYPICALLY ON RECESS, SCHEDULES ARE DIFFERENT THIS YEAR. THEY WERE IN SESSION FOR MUCH OF AUGUST. , THE AUTHORIZING COMMITTEE IN THE SENATE HELD A HEARING FOCUSING ON NIH. DR. COLLINS TESTIFIED AND HAD DIRECTORS JOIN HIM INCLUDING DR. SHARPLESS. ALSO WANTED TO RECAP OTHER NCI COLLEAGUES SCIENTIFIC LEADERS ACROSS THE INSTITUTE HAVE BEEN INVITED TO SPEAK AT DIFFERENT BRIEFINGS AND EVENTS AT THE CAPITOL OVER THE PAST FEW MONTHS. AND SO YOU'LL SEE HERE AACR HOSTED A BRIEFING ON E-CIGARETTE ESEARCH AND DR. RACHEL GRANT AND TOBACCO CONTROL RESEARCH PRESENTED. THE PROSTATE HEALTH EDUCATION NETWORK HOSTS A SUMMIT EVERY SEPTEMBER AND INVITED A SPEAKER ABOUT THE RESPOND STUDY ON PROSTATE CANCER IN AFRICAN-AMERICAN MEN AND SUPPORTED UNDER THE MOONSHOT. DR. SHARPE LESS WAS INVITED TO GIVE THE KEYNOTE AT THE CONGRESSIONAL CHILDHOOD CANCER CAUCUS SUMMIT, AS WELL AS KEYNOTE AT A ONE VOICE AGAINST CANCER BRIEFING THIS FALL AND DR. MEG MOONEY JOINED COLLEAGUES AT ACS CANCER ACTION NETWORK PANEL FOCUSING ON OVERCOMING BEARERS TO CLINICAL TRIAL ENROLLMENT. IT'S BEEN A BUSY FEW MONTHS, WE APPRECIATED THE OPPORTUNITIES TO SHARE NCI'S WORK WITH CONGRESSIONAL COLLEAGUES. WE'VE HOSTED SOME VISITS AND MEETINGS. CONGRESSMAN KEVIN YODER WHO I MENTIONED ACTUALLY LOST HIS SEAT YESTERDAY, CURRENT CHAIR OF THE HOUSE CANCER CAUCUS, INTERESTED IN COMING OUT TO NCI IN ADDITION TO HIS CANCER RESEARCH HAD AN INTEREST IN RARE DISEASE AND PEDIATRIC RESEARCH, MET WITH DR. SHARPLESS AND DR. WIEDEMANN, CHIEF OF PEDIATRIC ONCOLOGY BRANCH AND SEVERAL OF HER COLLEAGUES. DR. SHARPLESS ALSO MET WITH CONGRESSMAN BUTTERFIELD OF NORTH CAROLINA, ONE OF THE CO-CHAIRS OF THE CHILDHOOD CANCER CAUCUS BUT UNFORTUNATELY THE DAY OF THEIR SUMMIT WAS THE DAY HURRICANE FLORENCE WAS HITTING THE NORTH CAROLINA COAST SO HE WAS IN HIS DISTRICT, DR. SHARPLESS FOLLOWED UP WITH HIM LATER IN THE MONTH. I WANTED TO SAY A FEW WORDS ON BILLS CONGRESSMAN BUTTERFIELDWO WAS A LEAD SPONSOR WITH COLLEAGUES IN THE HOUSE AND SENATE. I KNOW M.K. MENTIONED THESE TWO BILLS TO YOU IN JULY SO I'LL KEEP THE BACKGROUND BRIEF, HIGHLIGHTING SOME ACTIVITIES ON EACH OF THESE. NCI IS WORKING WITH COLLEAGUES AT THE FDA, ON IMPLEMENTING THIS SECTION OF THE FDA REAUTHORIZATION ACT, AS BASED ON PRIOR STAND-ALONE PROPOSAL, RACE FOR CHILDREN ACT, AND GIVES THE FDA THE ABILITY WHEN ONCOLOGY DRUGS ARE FOCUSING ON MOLECULAR TARGETS THAT ARE SHARED ACROSS ADULT AND PEDIATRIC CANCERS TO REQUIRE ACTIVITY SEEKING AND DOSING STUDIES, PEDIATRIC STUDIES, AND SO PART OF THAT BILL REQUIRED FDA TO DEVELOP THESE MOLECULAR TARGET LISTS AND TO WORK WITH NCI TO DO SO AND THAT'S SOMETHING WE'LL BE CONTINUING TO UPDATE AND THOSE LISTS WERE POSTED ON FDA'S WEBSITE IN AUGUST. A MORE RECENT LAW, CHILDHOOD CANCER STAR ACT, SIGNED INTO LAW IN JUNE, INCLUDING PROVISIONS TO NCI, NIH, CDC, FOCUSING ON CHILDHOOD, ADOLESCENT AND YOUNG ADULT CANCER SURVIVORSHIP RESEARCH AND OPPORTUNITIES TO ENHANCE BIOSPECIMEN COLLECTION AND RESOURCES. SO IMPLEMENTATION AND PLANNING IS UNDERWAY THERE AS WELL. IT ALSO INCLUDES PROVISIONS ENCOURAGING NCI TO INCLUDING PEDIATRIC EXPERTISE ON ADVISORY BOARDS AND WE VALUE THE EXPERTISE OF COLLEAGUES AT CTAC, PROVIDING THEIR INPUT TO THE GROUP. IN TERMS OF RESEARCH PROVISIONS, COLLEAGUES AT NCI ARE WORKING ON FUNDING OPPORTUNITY ANNOUNCEMENT ON SURVIVORSHIP RESEARCH AND EXPECT THAT TO GO TO BOARDS FOR APPROVAL IN DECEMBER. AND COLLEAGUES ARE ASSESSING OPPORTUNITIES TO ENHANCE BIOSPECIMEN RESOURCES, M.K. AND I WILL HAVE UPDATES AT FUTURE MEETINGS ABOUT THIS. ONE FINAL LONG-TERM LEGISLATIVE EFFORT, DR. SHARPLESS TALKED THIS MORNING ABOUT OUR ANNUAL PLAN AND PROFESSIONAL JUDGMENT BUDGET, THIS IS A UNIQUE AUTHORITY WE HAVE UNDER THE NATIONAL CANCER ACT OF 1971 AND SO EACH YEAR WHEN THIS PLAN IS AVAILABLE OUR OFFICE SENDS IT TO EVERY CONGRESSIONAL OFFICE TO THE HEALTH LEGISLATIVE ASSISTANTS, TO EACH MEMBER OF CONGRESS AS WELL AS TO KEY COMMITTEE STAFF OF INTEREST WHO WILL FIND IT OF INTEREST AND SO WE MAKE A POINT TO HIGHLIGHT DR. SHARPLESS HAD MENTIONED THIS YEAR'S PLAN REALLY FOCUSES ON SEVERAL PATIENT AND RESEARCHER STORIES, INCLUDING FORMER CTAC MEMBER DR. EDITH MITCHELL WHO YOU SEE UP THERE. WE MAKE A POINT TO HIGHLIGHT WHEN THOSE STORIES ARE FROM A MEMBER STATE OR DISTRICT. WE PAY CLOSE ATTENTION TO THE DIFFERENT CANCER CAUCUSES TO HIGHLIGHT RESEARCH AREAS OF INTEREST, AND TO HIGHLIGHT IF A MEMBER HAS A PERSONAL INTEREST IN THE CANCER RESEARCH AREA, SO THIS IS A NICE OPPORTUNITY AS WELL TO SHARE NCI'S WORK WITH OUR CONGRESSIONAL COLLEAGUES. SO I WILL WRAP IT UP THERE. I WANT TO MAKE SURE YOU HAVE MY CONTACT INFORMATION. I'M HAPPY TO TAKE QUESTIONS HERE TODAY. AS THE MEETING IS WRAPPING UP, FEEL FREE TO REACH OUT OR PUT OUR GOVERNMENT RELATIONS TEAM IN CONTACT WITH OUR TEAM. I'D BE HAPPY TO TALK MORE. THANKS AGAIN FOR HAVING ME TODAY. >> QUESTIONS FOR HOLLY. IF YOU'RE HEAD OF A CAUCUS YOU WON'T GET RE-ELECTED? >> I WAS HIGHLIGHTING CHANGES. SEVERAL CAUCUS LEADERS ARE MAINTAINING SEATS AND MAINTAINING LEADERSHIP POSITIONS. THAT WAS REALLY JUST TO HIGHLIGHT SOME MEMBERS THAT HAD PARTICULAR INTEREST IN DIFFERENT CANCER RESERVE AREAS. YEAH, MANY ARE STICKING AROUND AND WILL CONTINUE TO WORK WITH THEM AS WELL AS WITH THE NEW MEMBERS. >> GREAT. WALLY? >> THANKS FOR THAT GREAT UPDATE. I SHOULD PROBABLY KNOW THIS BUT WHAT'S THE PROCESS AND TIMELINE TO WHEN WE'LL KNOW WHO THE NEW COMMITTEE LEADERS ARE IN CONGRESS NOW THAT DEMOCRATS HAVE A MAJORITY AND IS IT USUALLY THE SENIOR DEMOCRATIC MEMBERS OF THE COMMITTEES AND DO WE HAVE ANY FEELING ABOUT THEIR VIEW AND NIH/NCI RESEARCH? >> SURE. THERE'S SOME LEADERSHIP RACES ALREADY KICKING OFF RIGHT NOW, MINORITY LEADER IN THE HOUSE, KEVIN MCCARTHY AND JIM JORDAN WILL BE RUNNING. WE'LL HAVE TO SEE WHO THE HOUSE SPEAKER WILL BE, HEADING INTO THE NEW CONGRESS, SO THOSE BIG RACES WILL BE HAPPENING MORE DIRECTLY RELATED TO NIH AND NCI, THESE COMMITTEE RACES, THAT I MENTIONED. THEY ARE ACTUALLY -- THERE LIKELY WON'T BE MUCH TURNOVER IN LEADERSHIP OF OUR SUBCOMMITTEES OF INTEREST, ASIDE FROM THE FACT I MENTIONED HOUSE APPROPRIATIONS COMMITTEE WILL HAVE A NEW RANKING MEMBER OF FULL COMMITTEE, TOM COLE, KATE GRANGER, A COMPETITIVE RACE. IF CHAIRMAN COLE BECAME THE RANKING MEMBER WOULD HE HOLD THAT OF OUR SUBCOMMITTEE, HE COULD, WE DON'T KNOW WHAT THAT WILL LOOK LIKE, THE BIGGEST POTENTIAL CHANGE FOR COMMITTEES WE INTERACT WITH MOST OFTEN BUT WE'LL SEE MANY SAME LEADERS WHO ARE STRONG SUPPORTERS OF NIH AND NCI SO ON THE SENATE SIDE WE HAVE CHAIRMAN ROY BLUNT OF OUR LABOR HHS SUBCOMMITTEE OF THE APPROPRIATIONS COMMITTEE AND RANKING MEMBER PATTY MURRAY, THAT LIKELY WILL NOT CHANGE. ON THE HOUSE SIDE THE FORMER RANKING MEMBER NOW CHAIR OF OUR SUBCOMMITTEE WILL BE DELAURA OF CONNECTICUT, CHAIRMAN EVER FULL COMMITTEE LOWY OF NEW YORK, LONGTIME RANKING MEMBER, ALL VERY INTERESTED IN NIH AND NCI AND HAVE VOICED STRONG SUPPORT IN THE PAST AND OUR AUTHORIZING COMMITTEE LEADERSHIP MAY SHIFT A SEATS WILL JUST SHIFT TO THE MAJORITY AND MINORITY IN THE HOUSE, AND NOT NECESSARILY WHO HOLDS THE POSITION. >> HOLLY, GREAT PRESENTATION. THE BLUEPRINT IS NON-BINDING, MORE SO THAN EVER CONGRESS SEEMS TO HAVE ITS OWN MIND WHEN IT COMES TO NIH FUNDING BUT THAT SAID, WHAT'S THE NCI NUMBER THAT THEY ARE ENCOURAGING TO GO INTO THE PRESIDENT'S BUDGET BLUEPRINT THIS NEXT ROUND, IS IT SOMETHING BASED OFF THE BYPASS BUDGET OR SOMETHING THAT YOU'LL WORK OUT WITH OMB? >> THAT'S SOMETHING WE WORK WITH OMB AND NIH AND HHS. THE PROFESSIONAL JUDGMENT BUDGET, BYPASS BUDGET, THE UNIQUE AUTHORITY TO SAY IN A PERFECT WORLD WHAT COULD WE DO WITH ADDITIONAL RESOURCES, WHAT WOULD THAT LOOK LIKE. THE PRESIDENT'S BUDGET IS DEVELOPED CLOSELY WITH OMB, HHS AND NIH AND STILL UNDER DEVELOPMENT SO I CAN'T REALLY SPEAK TO A SPECIFIC NUMBER. >> YOU MENTIONED THIS LUXURY OF HAVING A BUDGET TO WORK WITH THIS YEAR. WHAT'S THE CHANCE THIS KIND OF CHANGE WILL LEAD TO REININSTALLATION NEXT YEAR? >> IT'S HARD TO SAY. I TRY NOT TO MAKE PROJECTIONS, AND I THINK YOU HAVE TO TAKE INTO ACCOUNT THAT THIS YEAR THE ELECTION CREATED SOME PRESSURE. AND SO I DO THINK THAT WAS A FACTOR. I KNOW OUR APPROPRIATIONS LEADERSHIP AND LIKE I JUST SAID WE'LL SEE MANY OF THE SAME LEADERS IN VARIOUS POSITIONS IN THE NEXT CONGRESS ARE VERY COMMITTED TO TRYING TO RETURN TO REGULAR ORDER. AND HOPEFULLY IF FOLKS HAD A GOOD EXPERIENCE ON THE CONGRESSIONAL SIDE, ON THE EXECUTIVE SIDE WITH HAVING THIS ON-TIME FUNDING THIS YEAR HOPEFULLY THAT WILL BE SOMETHING TO LEARN FROM AS WELL. BUT IT MAY NOT GO QUITE AS SMOOTHLY NEXT YEAR AS IT DID THIS YEAR SO WE'LL SEE. I THINK IT'S A MOVE IN THE RIGHT DIRECTION BUT I'M NOT SURE IT'S SOMETHING THAT WILL HAPPEN EVERY YEAR. >> THANK YOU SO MUCH. >> YEAH, THANK YOU. >> VERY INFORMATIVE AND HELPFUL. WE'RE NOT SURE WHERE THE FUTURE LIES BUT YOU GAVE US A GREAT ROAD MAP. SO THE LAST FEW MINUTES I WANT TO HIGHLIGHT IN YOUR BINDERS WE HAVE THE FUTURE DATES FOR THE MEETINGS HERE. PUT THOSE ON YOUR CALENDARS. THERE WILL BE THE UPCOMING AGENDA, SOMETIMES WE'VE HAD THESE PLANNING GROUPS THAT MET AFTER THE SESSION. WE AREN'T GOING TO DO THAT TODAY. WE WILL BY PHONE TRY TO GET INFORMATION, ANY TOPICS THAT EACH OF YOU WOULD LIKE TO BRING UP, WE'LL TALK ABOUT THAT. IN THE AGENDA IN THE FUTURE OTHER WORKING GROUPS ARE STILL OUT THERE THAT WE'LL HAVE SOME REPORTS. GLIOBLASTOMA WORKING GROUP THAT WALLY IS LEADING, SMALL CELL LUNG CANCER WORKING GROUP, NTCN, BIOSPECIMEN BANK CONCEPT RENEWAL, CLINICAL TRIALS INFORMATICS WORKING GROUP UPDATE. WE'LL HAVE SOME. IF YOU HAVE IDEAS FOR FUTURE MEETINGS LET US KNOW. ANY FINAL THOUGHTS, ANY OTHER TOPICS? IF NOT, WE'LL -- LET ME DO THIS. THIS IS FUN. IT'S NOW ADJOURNED. [END OF PROGRAM]