>> HI, GUYS, WE'RE GOING TO GET STARTED. I'M AMY BULMAN, ACTING DIRECT TO OF ADVOCACY OFFICE HERE AT THE CANCER INSTITUTE. MOST OF YOU KNOW ME OR HAVE KNOWN ME AND IF NOT, I LOOK FORWARD TO TALKING TO YOU THROUGHOUT TODAY. WE'RE VERY EXCITEDDED ABOUT TODAY'S MEETING. THANK YOU SO MUCH FOR TAKING THE TIME OUT TO COME BE US WITH ON CAMPUS AND P MANY OF YOU SPEND TIME WITH US WORKING ON THIS AGENDA AND SPEAKERS AND CONTENT AND QUESTIONS WE NEED TO ADDRESS SO WE VERY MUCH APPRECIATE THAT. BEFORE I TURN IT OVER TO MAX OUR CHAIR I WANT TO LET YOU KNOW THERE'S A HANDFUL OF PEOPLE IN THE ROOM, ALSO PEOPLE ON VIDEOCAST JOINING US THAT WAY, WE APPRECIATE YOU TAKING TIME TO TALK ABOUT THIS IMPORTANT TOPIC. >> GOOD MORNING. I'M MAX WALLACE, CHAIR OF THE DCLG. I WANT TO TELL YOU HOW WONDERFUL TO HAVE EVERYBODY IN THE ROMP AND SO MANY COME FROM LONG DISTANCE TO TAKE PART IN THIS. IT WILL MAKE IT A BETTER EVEN OR DISCUSSION. IT GLADDENS MY HEART TO SEE Y'ALL HERE. NOW I'M GOING TO REVERT TO MY OLD PROFESSION AND BE A LAWYER FOR A SECOND AND READ AN OPENING STATEMENT BECAUSE I WANT US TO BE PROPERLY COMPLIANT. AND IT'S A CONFLICT OF INTEREST STATEMENT THAT SAYS AS COMMITTEE MEMBERS I WANT TO REMIND YOU TO ABSENT YOURSELF DURING SPECIFIC DISCUSSIONS FOR YOUR PARTICIPATION ON A PARTICULAR PRODUCT PROGRAM OR OTHER SPECIFIC PROGRAM THAT CREATES A CONSTITUTE OF CONFLICT OF INTEREST OR APPEARANCE OF ONE. ABSTAIN FROM ANY PARTICIPATION AN DISCUSSION OR ACTION REGARDING THAT MATTER. IN LIGHT OF CURRENT POLICIES GOVERNING CONFLICT OF INTEREST BASED ON FINANCIAL HOLDINGS OF SPECIAL GOVERNMENT EMPLOYEES, THIS WILL ONLY GO ON FOUR OR FIVE MORE MINUTES. WHICH INCLUDE ALL MEMBERS OF THE COMMITTEE. WE MUST DEPEND ON YOU TO VOLUNTARILY ABSENT YOURSELF DURING DISCUSSION OF MATTERS THAT COULD CONCEIVABLY IMPACT THE STATUS OF THE HOLDINGS. WE TRUST YOUR JUDGMENTS IN THESE INSTANCES. A QUORUM OF BOARD MEMBERS IS REQUIRED FOR EACH INSTANCE A VOTE OCCURS IN OPEN SESSION, DURING THESE MEETINGS A MINIMUM OF 6 APPOINTED MEMBERS MUST BE PRESENT TO VOICE THEIR VOTES. NEW MEMBERS ARE NOT VOTING UNTIL THEY HAVE BEEN CLEARED BY THE NCI ETHICS OFFICE. THIS CAUSES ME TO SMILE BECAUSE IN MY ENTIRE CAREER AS MEMBER OF THE DCLG WE HAVE NEVER HAD ONE VOTE BUT IT'S IMPORTANT THAT YOU UNDERSTAND WHAT THESE RULES AREMENT DON'T HOLD YOUR BREATH. >> WE DID VOTE ON THE NAME CHANGE BUT I DON'T THINK ANY OF US HAD A CONFLICT OF INTEREST. WE ARE STILL CALLED THE DCLG, THERE ARE AT LEAST 12 MORE LEVELS GOVERNMENT BUREAUCRACY IT HAS TO GO THROUGH BEFORE WE CHANGE OUR NAME. WE WILL BECOME COUNCIL OF RESEARCH ADVOCATES INSTEAD OF DIRECTOR CONSUMER LIAISON GROUP BUT DON'T KNOW WHEN WE'LL BECOME THAT. HAROLD APPROVED. I ALSO LIKE TO START AND WELCOMENATE GAINS OUR NEW MEMBER, WILL YOU TELL US WHERE YOU ARE? MEG IS ASSOCIATE DEAN FOR ACADEMIC AFFAIRS AND PEENSIAL LEARNING AND DIRECTOR CENTER FOR PATIENT PARTNERSHIP UNIVERSITY OF WISCONSIN LAW SCHOOL, GREAT ADDITION TO OUR GROUP. I WANT TO GIVE AN OVERVIEW WHY WE HAVE THIS MEETING NOW. I ATTRIBUTE TO TO OUR FRIEND DAVID AIRPLANE FROM THE BRAIN TOW MORE SOCIETY. DAVE IS WORKING ON A PROJECT IN BRAIN CANCER ROOK AT BASICALLY THESE SAME TIMES OF ISSUES. WE WERE PRIVILEGED TO BE INVITED TO PARTICIPATE IN THAT SET OF DISCUSSIONS, I THOUGHT THIS IS SO MUCH BROADER, SO MUCH MORE IMPORTANT THAN JUST WHAT WE'RE SEEING IN BRAIN CANCER, IT MAKES SENSE TO BRING IT BEFORE THE DCLG. AND FOR MANY MANY GUESTS WE HAVE IS THE COMMITTEE TO ADVISE SENIOR OFFICERS, THE NCI ON ISSUES WE'RE ASKED TO ADVISE ON AND ISSUESES WE THINK IT'S IMPORTANT TO ADVISE ON. THIS IS A TIME OUR INTERESTS MEET THAT THE SCENE YEAR LEADERSHIP WOULD LIKE TO HEAR ABOUT THIS, WE WANT TO BECOME EDUCATED SO THIS ISN'T AN NCI MEETING. THIS IS A MEETING OF A GROUP OF ADVOCACY ORGANIZATIONS CHARTERD TO ADVISE THE DIRECTOR. WE'RE COUNTING YOU PART OF US FOR THIS PURPOSE. OUR JOB IS TO BAND TOGETHER WITH YOU TO LEARN TODAY FROM EACH OTHER. AND TO SEE WHERE WE CAN TAKE THIS IN A WAY THAT WILL BE USEFUL TO HELP NCI GUIDE ITS FUTURE PATH. , IT'S GREAT TO HAVE EVERYBODY BANDED TOGETHER Z Z THE ADVANTAGE IS WE COME OUT AS TEAMMATES FROM SOMETHING LIKE THIS. SO PLEASED TO HAVE YOU HERE AND LOOK FORWARD TO HEARING WHAT EVERYBODY HAS TO SAY. WE SUPPORT THE LARGER CANCER COMMUNITY TRYING TO FIND MORE EFFICIENT PATHS TO DEVELOPING NEW TREATMENTS ACROSS THE BOARD IN CANCER. THAT'S WHAT A LOT OF US ARE LOOKING FOR, WHY WE'RE SUPPORTIVE OF THE RESEARCH NCI DOES, A LOT OF ORGANIZATIONS FUND BOTH TYPES OF CANCER RESEARCH BUT AS I HAVE TALKED TO THE THOUGHT IS WE OUGHT TO BE LOOKING AT ADDING VERY SPECIFIC PEDIATRIC FOCUS TO THE DCLG ITSELF AND WE'LL PUT A CONCERTED EFFORT ADDING PEOPLE INTO THE DCLG GOING FORWARD TO PROVIDE A VERY SPECIFIC PEDIATRIC VOICE SO EVERY DISCUSSION AROUND THE TABLE THAT'S FRONT AND CENTER. SO I KNOW YOU ARE HEAR BECAUSE YOU WANT YOUR VOICES HEARD AND OUR INTENTION IS TO DO THIS ON A GO-FORWARD BASIS. DURING THE DAY YOU CAN SEE I THINK Y'ALL GOT COPIES OF THE AGENDA. YOU SHOULD HAVE. WE HAVE WONDERFUL SPEAKERS, WE'RE GOING TO GO THROUGH THIS, THIS IS DESIGNED TO EDUCATE US AS COMMITTEE OF ADVOCATES SO WITH WANT TO LEARN FROM VARIETY OF SOURCES. I WOULD LIKE IT TO BE INTERACTIVE AS POSSIBLE. I WOULD LIKE IT TO BE AS ORGANIZED AS POSSIBLE. I RUN MY ORGANIZATION AND COMPANIES BUILT ON FOUR PRINCIPLES, FAIRNESS HONESTY, TRUST AND RESPECT, THOSE ARE THE GRADING CRITERIA IN OUR ORGANIZATIONS. I WOULD LIKE THOSE TO GOVERN OR MEETING TODAY. WE'RE HERE BECAUSE WE ALL WANT TO DO GOOD STUFF AND LET'S RESPECTFUL AND FAIR TO EVERYBODY AND THINKING HOW WE'RE GOING FORWARD. WITH THAT SAID, WE'RE GOING TO DEVIATE A LITTLE BECAUSE IT'S SO IMPORTANT WE HAVE SO MANY NEW FRIENDS IN THE ROOM MAYBE HE SHOULD SHOULD INTRODUCE THEMSELVES. WE CAN START AROUND THE TABLE, I'M MAX WALLACE, I RUN AN ORGANIZATION CALLED ACCELERATE BRAIN CANCER CURE. WHICH IS HERE IN WASHINGTON D.C. AND FOCUSES ON BRAIN TUMORS. I'M AMY BULMAN ADVOCACY OFFICE AT NCI AND SPECIAL ASSISTANT TO DR. DOUG LOWIE DEPUTY DIRECTOR. >> I'M ANN (INAUDIBLE) DEPUTY DIRECTOR AT NCI AND SPENT MANY YEARS WORKING CLOSELY WITH OFFICE OF ADVOCACY RELATIONS. Q. GOOD MORNING I'M JOANNE HARRIS. I WORK ON THE EXTRAMURAL RESEARCH DEPARTMENT AMERICAN CANCER SOCIETY. >> GOOD MORNING, JOHN (INAUDIBLE) FROM THE AMERICAN ASSOCIATION FOR CANCER RESEARCH. I'M MANAGING DIRECTOR FOR SCIENCE POLICY AND GOVERNMENT AFFAIRS. >>TY I'M LEE HELMAN, SCIENTIFIC DIRECTOR FOR CLINICAL RESEARCH AT THE CENTER FOR CANCER RESEARCH WHICH IS THE INTRAMURAL NCI PROGRAM AND ALSO SENIOR INVESTIGATOR IN THE PEDIATRIC ONCOLOGY BRANCH. >> I'M MALCOLM SMITH, PEDIATRIC ONCOLOGIST WITH THE CANCER THERAPY EVALUATION PROGRAM AT NCI AND I WORK ESPECIALLY WITH THE PEDIATRIC BRAIN TUMOR CONSORTIUM AND CHILDREN'S ONCOLOGY GROUP. >> MY NAME IS JOHN MARIS, PHYSICIAN SCIENTIST AT CHILDREN'S HOSPITAL PHILADELPHIA. >> I'M PETER ADOCUMENTSON PEDIATRIC ONCOLOGIST CHILDREN'S HOSPITAL PHILADELPHIA, I CHAIR THE CHILDREN'S ONCOLOGY GROUP. >> I'M GREGORY (INAUDIBLE) PEDIATRIC ONCOLOGIST, I'M CURRENTLY ASSOCIATE DIRECTOR OF THE OFFICE OF HEMATOLOGY ONCOLOGY PRODUCTS AT THE MDA. AND ALSO AT THE CHILDREN'S NATIONAL MEDICAL CENTER IN WASHINGTON D.C. >> ANDREA FERRIS, I RUN LONGEVITY FOUNDATION LUNG CANCER RESEARCH. >> MICHELLE KEITH, ASR.IATE DIRECTOR FOR SCIENCE AT CENTER FOR DEVICES AND RADIO LOGICAL HEALTH AT FDA WHICH OVERSEES MEDICAL DEVICES AND DIAGNOSTICS. >> TED THE GAINS ASSOCIATE DEAN FOR EXPERIENCIAL LEARNING UNIVERSITY OF WISCONSIN AND FOUNDER DIRECTOR FOR CENTER FOR PATIENT PARTNERSHIPS, PRESIDENT UNIVERSITY OF WISCONSIN IN MADISON. >> DAVID CANCER, SENIOR PUBLIC POLICY NATIONAL BRAIN TUMOR SORT. >> SUSAN (INAUDIBLE) CEO OF THE (INAUDIBLE) FOUNDATION FOR CANCER RESEARCH AND JUST A QUICK NOTE, THOSE OF YOU BASKETBALL FANS, AND P KNOW DICK VITAL, A HUGE PROPONENT OF ADVOCATE FOR PEDIATRIC CANCER RESEARCH, HE'S ON THE BOARD AND HE'S READY TO KEEP MOVING AS WE ALL ARE. IT'S IMPORTANT. >>TY I'M JOHN CZAJKOWSKI, DEPUTY DIRECTOR FOR MANAGEMENT NCI AND EXECUTIVE OFFICER. SO I'M MANAGEMENT ADMINISTRATION HERE AT THE INSTITUTE. >> WE'LL START IN THE BACK. >> PETER MAY BERRY, SENIOR MANAGER OF LEGISLATIVE AFFAIRS FOR THE STEVE ALDRIDGE FOUNDATION. >> VICKIE BIGGER, PRESIDENT OF THE COALITION AGAINST CHILDHOOD CANCER. >> SARA BONDU, LOBBIEST FOR AMERICAN CANCER SOCIETY CANCER ACTION NETWORK. >> RUTH HOFFMAN, DIRECTOR OF CHILDREN'S NATIONAL CANCER ORGANIZATION. >> I'M MAUREEN LILY, EXECUTIVE DIRECTOR OF CHILDREN'S CAUSE FOR CANCER ADVOCACY. >> (INAUDIBLE) PRESIDENT OF THE COALITION AND ORGANIZATION MY WIFE AND I STARTED (INAUDIBLE) PASSED AWAY FROM (INAUDIBLE) IN 2010. >> I'M JACQUELINE PETRO, CANCER SURVIVOR AND CHILD CANCER ADVOCATE. >> I'M MIKE GELLETTE, WITH TRUTH (INAUDIBLE) A DOCUMENTARY AND SOCIAL MEDIA CAMPAIGN. >> ? I'M MAKING MY WAY AROUND. >> WHY DON'T YOU INTRODUCE YOURSELF. >> LATONIA HENDRICK, I'M A FORMER NCI AND CONSULTANT TO THE OFFICE OF ADVOCACY RELATIONS. >> I'M (INDISCERNIBLE) NCI COORDINATING CENTER FOR CLINICAL TRIALS, I'M PROGRAM DIRECTOR FOR THE PEDIATRIC STEERING COMMITTEE. >> HELLO, I'LL DANIELLE DAY WITH OFFICE OF SCIENCE PLANNING AT NCI. >> I'M M.K. HOLLAHAN OFFICE OF GOVERNMENT CONGRESSIONAL RELATIONS. >> SUSAN HERBSON, ALSO WITH NCI GOVERNMENT CONGRESSIONAL RELATIONS. WE HAVE A LITTLE CONTINGENCY HERE. >> HOLLY GIB BONNES WITH LEGISLATIVE OFFICE. >> (INDISCERNIBLE) ALSO WITH THE LEGISLATIVE OFFICE. >> I'M AMY (INDISCERNIBLE) WITH THE LEGISLATIVE OFFICE, DIRECTOR OF PUBLIC POLICY FOR CANCER ADVOCACY. >> I'M KATHERINE WARREN, PEDIATRIC ONCOLOGY BRANCH AND MEMBER OF THE PEDIATRIC BRAIN CHILDREN CONSORTIUM AND CHILDREN'S ONCOLOGY GROUP. >> I'M ROBERT PRICE OFFICE OF ADVOCACY RELATIONS. >> >>TY I'M CONSUL TAN TO NCI SERE PROGRAM WHICH PRODUCES STATISTICS ON INCIDENCE MORTALITY AN SURVIVAL. >> I'M JENNIFER CLICK, WITH THE (INDISCERNIBLE) AND MOTHER OF AN 11 YEAR SURVIVOR OF STAGE 4 NEUROBLASTOMA. >> MARGARET NORRIS, MY SON WAS DIAGNOSED WITH T-CELL ALL, AUGUST 2008. RELAPSED 2010, TOOK HIS LAST CHEMO THREE WEEKS AGO TODAY. >> I'M DANIELLE LEECH BOARD MEMBER OF THE CHILDHOOD CANCER ORGANIZATION AND PARENT OF A -- MY SON MASON PASSED AWAY FROM MEDULLAR BLASTOMA AT AGE FIVE. >> ERICA NEWFELT VICE PRESIDENT OF GOVERNMENT RELATIONS AN PROGRAM DIRECTOR RESEARCH CANCER. >> I'M WITH THE OFFICE OF COMMUNICATIONS NATIONAL CANCER INSTITUTE. >> JENNIFER GLOCK WITH ADVOCACY OFFICE AT NCI. >> I'M PETER GARRETT SENIOR ADVISER TO DR. HAROLD VARMUS FOR COMMUNICATIONS. >> RICHARD (INAUDIBLE) RETIRED ATTORNEY FOR THE MAX CURE FOUNDATION IN HONOR OF ANIMY GRANDSON MAX, WHO IS NOW A SIX YEAR SURVIVOR, TEN YEARS OLD. IF YOU SAW TODAY'S SHOW LAST WEEK WE WERE FEATUREDDEN ON IT. >> KELLY LANDY, OFFICE OF ADVOCACY RELATIONS. >> DOOR NETA KING WITH NCI. >> JOHN MCINTOSH, I LOST MY NINE-YEAR-OLD DAUGHTER TO A BRAIN TUMOR AND SINCE THEN WORKING WITH CURE SEARCH NOW AND COLLABORATIVE AND VARIOUS OTHER ADVOCACY GROUPS AS AN ADVOCATE. >> THANK YOU ALL. WE'RE SO PLEASED YOU'RE HERE. I THINK IT'S INTERESTING TO KNOW WILLINGNESS OF NCI TO COMMIT SO MUCH TIME TO COME TO THIS MEETING FROM ACROSS THE BOARD WITH VERY SENIOR OFFICERS IN IMPORTANT PLACES. A LOT OF PEOPLE DON'T WANT TO TAKE ADVICE, SOMETIMES WE WANT TO GIVE IT AND THEY DON'T WANT TO TAKE IT AND WHAT'S GRATIFYING TO ME AS CHAIR OF THIS VOLUNTEER GROUP IS NCI REALLY EMBRACED THIS AND SAID THIS IS GOING TO BE SUCH A GOOD START OF A PROCESS WHERE WE CAN ALL LEARN FROM EACH OTHER SO I WANT TO THANK YOU FOR TAKING TIME OUT OF YOUR WORK DAY TO COME DO THIS AS WELL AS OUR GUESTS. WITH THAT SAID, I WOULD LIKE TO COME BACK TO JOHN CZAJKOWSKI TO MY RIGHT, ONE PRIVILEGE BEING IN THE DCLG COMMUNITY IS WE GET UPDATED WHEN WE HAVE MEETINGS ON THINGS HAPPENING AT NCI IN THEIR WORLD THAT THEY THINK ARE RELEVANT FOR US TO KNOW. I LOOK FORWARD TO HEARING FROM JOHN BECAUSE I THINK HE GIVES US SUCH A GOOD VIEW OF NCI, IT'S NOT ALWAYS CHEERY IN THIS ECONOMIC ENVIRONMENT SINCE HIS JOB IS TO MAKE THIS SHIP RUN WELL. SUNSHINE IS HARD TO COME BACK. BUT IT'S IMPORTANT TO KNOW THIS AND I'M PLEASED WHEN HE'LL COME JOIN US. SO JOHN. >> IT IS ABOVE FREEZING. AS HAPPY AS I'M TO SEE YOU I'M ALSO HAPPY GOOD MORNING, IT'S GOOD TO SEE YOU AND MEET SO MANY NEW PEOPLE COMMITTED TO THIS DISCUSSION. LOOKING BACK ON A YEAR LIKE THIS, LISTENING TO YOUR COMMENTS, IT'S ONE UP THING TO PROVIDE AN UPDATE, I WILL NOT ATTEMPT TO EXPLAIN OR HELP UNDERSTAND WHAT HAS GONE OVER THE PAST YEAR IN THE FEDERAL SECTOR WHEN IT COMES TO THE BUDGET PROCESS. IF THE SEQUESTER WAS A SURREAL EXPERIENCE, THE SHUTDOWN IN OCTOBER WAS ALMOST INCOMPREHENSIBLE. AND I THINK IN MANY WAYS THE CONSEQUENCES OF THAT SHUTDOWN ARE ALMOST IMMEASURABLE. FOR US, LIKE ANY GOOD CRISIS WE LIKE TO SEIZE THE MOMENT AND TAKE A HARD LOOK AT OURSELVES AND THINK ABOUT NOT JUST PROGRAMS AND THE NCI AS EXISTS TODAY BUT THINK ABOUT OUR PROCESSES FOR SETTING PRIORITIES AND MAKING DECISIONS WITH PRECIOUS RESOURCES. THE BUDGET ENVIRONMENT WON'T GET BETTER ANY TIME SOON. THE PRESIDENT'S BUDGET PLANS ARE TALKING ABOUT SOME RELIEF TO THE AUSTERITY THAT HAS BECOME THE NORM FOR THE PAST COUPLE OF YEARS. WE HAVE LOTS OF FRIENDS AND SUPPORTERS BUT THEY'RE BROKE. SO THEIR ENTHUSIASM DOESN'T ALWAYS COME WITH THE FINANCIAL RESOURCES WE SEE TO DO THIS IMPORTANT WORK. I THINK WHAT'S EXTRAORDINARY FOR ME THE REASON I LIKE TO COME TO THIS GROUP IS TO IMPRESS UPON YOU AS BEST I CAN HOW IMPORTANT THIS RELATIONSHIP IS TO THIS INSTITUTE BECAUSE JUST AS SUNSHINE IS HARD TO COME BY, CONSTRUCTIVE DIALOGUE HAS BEEN A SCARCE COMMODITY IN THIS TOWN FOR SEVERAL YEARS. IT IS HARD TO COME UP WITH SOLUTIONS AND PLANS AND STRATEGIES AND PRIORITIES THAT THRILL ANYBODY, EVERYBODY IS GIVEN A LITTLE SOMETHING THESE DAYS, EVERY PART OF THIS PROGRAM HAS A CONSTITUENCY OF SOME KIND. UNFORTUNATELY AS WE HAVE SEEN IN THE BIG PICTURE POLITIC THES THAT GO ON DOWNTOWN WASHINGTON THAT OFTEN DEGRADES TO A FISTFIGHT THAT IS OFTEN MORE DAMAGING AS GOVERNOR O'MALLEY SAID TO ME ONE DAY WHEN THE ELEPHANTS FIGHT EVEN GRASS GETS TRAM TRAMPLED. WE HAVE SEEN TOO MUCH OF THAT, MARKEDLY DIFFERENT IN THIS ROOM KNOWING THE PASSION THAT WE ALL FEEL, ESPECIALLY WHEN IT COMES TO CHILDREN. TO BE ABLE TO SIT AS ADVOCATES FOR IMPORTANT PRINCIPLES, ACCEPT OUR DIFFERENCES, ACCEPT OUR PERSPECTIVES AN P TRY CONSTRUCTIVELY TO FIND WAY FORWARD WE CAN SIGN ON TO IS FRANKLY, A REFRESHING CHANGE OF PACE FROM WHAT WE SEE FROM OUR FRIENDS ON THE HILL SO I JUST HOPE BY BEING HERE, ALL OF US WHO ARE HERE WITH ANN AND AMY AND LEE AND PETER AND EVERYBODY ELSE WHO IS HERE FROM NCI, I HOPE YOU DO SEE HOW VALUABLE THIS RELATIONSHIP IS TO US. WE ARE EACH OTHER'S EYES AN EARS AN EACH OTHER'S VOICES IN DIFFERENT PLACES WE GO, WE HOPE THE UNITY AND SOL L DARETY THAT IS CREATED THAT EXISTS IN THIS ROOM AND CREATED IN THIS ROOM WE HOPE IT'S OBVIOUS TO YOU HOW MUCH IT MEANS TO US. THESE ARE TOUGH TIMES BUT AS WE LIKE TO SAY, AND AS OFTEN BEEN THE CASE, YOUR WORST NIGHT MARE CAN TURN TO YOUR FINEST HOUR IF YOU APPROACH IT WITH THE HEALTHY CONSTRUCTIVE DIALOGUE THAT WE'RE LOOKING FOR. THAW FOR TAKING PART AND BEING HERE. ON A PERSONAL NOTE, MY WIFE AND I HAVE FOUR CHILDREN, IT ISN'T LOST ON ME HOW IMPORTANT THIS WORK IS AND WHAT YOU GUYS WILL BE TALKING ABOUT TODAY WHICH IS WHY IT'S IMPORTANT TO GET OUT OF YOUR WAY AS QUICKLY AS POSSIBLE. I WANT TO SHARE WITH YOU A BIT OF PERSONAL NEWS, THIS IS A SELL P FISH MOMENT FOR ME BUT I WANT TO SHARE WITH YOU BECAUSE I HAVE WORKED SHOULDER TO SHOULDER WITH A NUMBER OF YOU FOR QUITE SOME TIME. I HAVE ACCEPTED AN OFFER TO JOIN HARVARD MEDICAL SCHOOL AS EXPECT PTIVE DEAN OF ADMINISTRATION START -- EXECUTIVE DEAN OF ADMINISTRATION IN JUNE. SO 27 YEAR RUN IN THE FEDERAL SECTOR IS GOING TO TAKE A BREAK IF I COME BACK TO FEDERAL SERVICE ONE DAY, WHO KNOWS. BUT AS MANY COLLEAGUES HEARD ME SAY, I HAVE NEVER BEEN ANYTHING OTHER THAN A CIVIL SERVANT. SO THIS AN EXCITING TIME FOR ME AND I'M SURE YOU CAN IMAGINE DISCERNMENT AND DECISION MAKING PROCESS FOR MY WIFE AND ME. BUT IT IS AN FIGHTING PROPECK -- EXCITING PROJECT AND A CAREER IN ACADEMIA I LOOKED FORWARD TO FOR SOME TIME SO I'M CHANGING TEAMS BUT I DON'T THINK I'M GOING TO DISAPPEAR BECAUSE THE WORK DONE IN THIS PLACE IS FAR TOO IMPORTANT AND SO I WANT TO CONTINUE TO ADVOCATE FOR THINGS THAT GET DONE HERE REGARDLESS OF WHERE I AM AND WHAT MY PROFESSIONAL ADDRESS IS. SO I SHARE THAT WITH YOU ON A PERSONAL NOTE I JUST REALLY THANK YOU FOR CONTINUING TO SHOW UP AND BE PART OF THIS DISCUSSION AND DO IT IN SUCH A HEALTHY CONSTRUCTIVE WAY IT MAKES NCI BETTER. LET'S ASK EACH OTHER HARD QUESTIONS AND LET'S DEAL WITH THE THORNY ISSUES. BUT KEEP EACH OTHER WRAPPED AROUND WHAT REALLY IS IMPORTANT AND KEEP THE DISCUSSION GOING FORWARD. SO THANK YOU FOR A FEW MINUTES, I KNOW WE SPENT SOME TIME AROUND THE ROOM, I DON'T WANT TO DELAY THE AGENDA FURTHER. IF ANYBODY WANTS TO ASK THE WORLD AS WE KNOW IT OR AS YOU IMAGINE IN THE FUTURE, I'M HAPPY TO SHARE, OTHERWISE I'LL LEAD YOU TO DO THE IMPORTANT WORK. I THANK YOU ALL TRULY. IT'S AMAZING. WE NEED A ROOM THIS BIG TO HAVE THIS DISCUSSION, THAT BY ITSELF SAYS SOMETHING. AS I TOLD YOU THANK YOU FOR ALL YOUR WORK AND I'LL GET U OUT OF YOUR WAY, THANK YOU, MR. CHAIRMAN. [APPLAUSE] >> J THANK YOU VERY MUCH, I WANT TO GRAB ON TO YOU AND SAY DON'T GO BUT THAT'S NOT FAIR BECAUSE YOU'RE GOING TO DO WONDERFUL THINGS IN A WONDERFUL PLACE. SO WE WISH YOU THE BEST OF LUCK. FOR THOSE WHO AREN'T REGULAR ATTENDEES, WE'RE FORTUNATE TO GET JOHN'S ADVISE BECAUSE HE GIVES US A STRAIGHT SHOOTING LOOK HOW HARD TO RUN A PLACE LIKE NCI WITHIN THE CONTEXT OF THE FEDERAL GOVERNMENT, BUSINESS TEEN AND BIZARRE POLICIES SOMETIMES. IT WILL BE INTERESTING TO SEE HOW YOU DO, I SUSPECT HARVARD IS JUST AS BYZANTINE. I WORKED IN ACADEMIA SO I UNDERSTAND. DURING YOUR TALK WE WERE FORTUNATE, NANCY JOINED US. WOULD YOU LIKE TO INTRODUCE YOURSELF? >> SORRY I'M TARDY, TOOK ME OF AN HOUR TO FIND THE ROOM. ANIMY NAME IS NANCY GOODMAN, I'M DIRECTOR OF KIDS VERSUS CANCER. WE FOCUS ON CREATING MARKET INCENTIVES FOR PEDIATRIC CANCER DRUG DEVELOPMENT. OUR SIGNATURE PROGRAM TO DATE HAS BEEN CREATING (INAUDIBLE) ENACTED AS THE RARE PEDIATRIC DISEASE PRIORITY REVIEW VENTURE PROGRAM AS PART OF THE FDA SAFETY INN INVESTIGATION ACT OF 2012. SO BE LOOKING FORWARD TO SPEAKING WITH ALL OF YOU AND DR. ADAMSON HERE TODAY. THANK YOU. >> THANK YOU. IT'S NOT UNUSUAL TO GET LOST AROUND HERE. I HAVE HAD EXACTLY THAT EXPERIENCE. THANK YOU. WE THOUGHT THE BEST WAY TO START MEETING LIKE THIS, WHICH REALLY STARTS TO BE EDUCATIONAL PROCESS AN DISCUSSION PROCESS TO GET THE SMARTEST THING TO TELL US THEIR VIEW OF THE STATE OF PEDIATRIC CANCER RESEARCH SO WE HAVE A FOUNDATION TO OPERATE FROM. WE ARE FORTUNATE TODAY. WE HAVE DR. JOHN MARIS FROM THE CENTER FOR CHILDHOOD CANCER RESEARCH CHILDREN'S HOSPITAL PHILADELPHIA WHICH IS A WONDERFUL PLACE DOING GREAT WORK WE'RE LUCKY TO GET JOHN TO COME, DR. MALCOLM SMITH, ASSOCIATE BRANCH CHIEF PEDIATRIC ONCOLOGY AND CTEP PROGRAM AT NCI. THAT WILL BE COMPLIMENTED BY DR. LEE HELMAN YOU HEARD FROM, THE SCIENTIFIC DIRECTOR FOR CLINICAL RESEARCH AND CENTER FOR CANCER RESEARCH HERE AT NCI. SO WE WILL START WITH TALK BUSINESS THE THREE GENTLEMEN TO FORM A PLATFORM AND FOUNDATION FOR THE REST OF THE DISCUSSION TO OCCUR DURING THE DAY. JOHN, WOULD YOU LIKE TO GO? >> JUST A SMALL HOUSEKEEPING NOTE. MOST OF Y'ALL HAVE SLIDES IN YOUR PACKETS FOR THOSE PRESENTERS, DR. MARIS THEY'RE NOT IN THERE YET BUT YOU'LL GET THEM SHORTLY. >> LIKE YOU ARE USUAL I DID THE SLIDES ON THE TRAIN RIDE DOWN, I APOLOGIZE FOR THAT. >> WE ALL KNOW IT. >> BEFORE WE GO, I WANT TO REMIND YOU THAT THIS IS BEING WEBCAST AND I KNOW A LOT OF YOU REPRESENT ORGANIZATIONS WITH CONSTITUENTS WHO WEREN'T ABLE TO COME BUT YOU SHOULD KNOW WITHIN A COUPLE OF DAYS THIS WILL BE AVAILABLE ONLINE AND YOU CAN GET BACK AND ACCESS WHICH IS A GREAT THING. SO PLEASE REMEMBER THAT AND ALSO PLEASE REMEMBER THERE ARE PEOPLE DIALED IN AS WELL. THANK YOU. >> SO IT'S MY PLEASURE TO BE HERE TODAY, I LOOK FORWARD TO LEARNING A LOT IT'S GREAT TO SEE OLD FRIENDS AND MEET NEW FRIENDS. I THINK THERE WILL BE REDEN DANCY IN WHAT MALCOLM AND LEE AND I HAVE TO SAY, THAT'S A GOOD THING HOPEFULLY THE POINTS WE WANT TO MAKE, THE ONES THAT WE FOCUS ON TO DRIVE THE POINT HOME. WE WERE EACH GIVEN SIX FRAMING QUESTIONS TO THINK ABOUT SO I THINK WE'RE GOING TO SPEAK WITHIN THAT CONTEXT BUT SINCE I'M THE FIRST TALK I THOUGHT I PROBABLY WOULD SHOW A FEW SLIDES EVERYONE HERE WILL BE UP TO SPEED ON BUT THOUGHT IT WOULD BE A GREAT WAY TO SET THE STAGE. I DO THINK THAT THOSE OF US ENGAGED IN THE PEDIATRIC CANCER PROBLEM AND INVESTIGATING WAYS TO IMPROVE OUTCOMES FOR THIS HORRIFIC SET OF DISEASES HAVE WITNESSED A MODERN MEDICAL SUCCESS STORY, IF YOU LOOK AT IMPROVEMENTS IN CURE RATES. P A OVER THE LAST SEVERAL DECADES. THIS PICTURE OF LEUKEMIA CELLS AND PICTURE OF A CHILD WITH A DISEASE BURKETT'S LYMPHOMA, TELL A LOT BUT THE BAR GRAPHS SPEAK FOR THEMSELVES AND SET THE STAGE HOW WE APPROACH THE PROBLEM OF CANCER IN GENERAL. I'M NOT GOING TO SPEND A LOT OF TIME ON RIGHT NOW, IS THAT THE INVESTIGATION OF PEDIATRIC CANCER THROUGHOUT H HISTORY OF INVESTIGATING CANCER HAS LED TO SEMINOLE ADVANCES IN UNDERSTANDING THE BASIC GENETIC OF THE DISEASE SO KEY CANCER GENES LIKE THE RETINAL BLASTOMA GENE, DISCOVERED BY STUDYING CHILDHOOD CANCER, THERE'S A HUGE LESSON THERE. CHILDHOOD CANCER IS BEING SOMEWHAT MORE PURE FROM AN ENVIRONMENTAL STANDPOINT. THERE'S LESS MUTATIONS DUE TO TOXINS AN EXPOSURES MAKE THEM MODEL SYSTEMS THAT PROVIDE INSIGHTS APPLICABLE TO THE PROBLEM OF CANCER IN GENERAL. THE OTHER SIDE OF THE COIN IS THERE ARE VERY IMPORTANT CHILDHOOD CANCERS WHERE THERE'S LITTLE OR NO IMPROVEMENT IN CURE RATES. A CHILD WHO PRESENTS WITH THIS CONDITION OF BRAIN STEM GLIOMA HAS THE SAME ZERO PERCENT CHANCE OF CURE THAN A CHILD PRESENTED WITH THIS MANY YEARS AGO WOULD HAVE. AND THE WAY WE TRADITIONALLY RESPONDED TO THIS REALITY AS PEDIATRIC ONCOLOGISTS OVER THE LAST SEVERAL DECADES HAS BEEN TO DRAMATICALLY INTENSIFY THE CYTOTOXIC THERAPY WE KNOW HOW TO PROVIDE. SO THE SAME STRATEGY THAT MADE THOSE MAJOR ADVANCEMENTS IN LIEU CHEMOIA AND OTHER DISEASES MORE CHEMOTHERAPY, MORE RADIATION H THERAPY HAS NOT RESULTED IN IMPROVEMENTS OR SIGNIFICANT OR ANYTHING MORE THAN INCREMENTAL IMPROVEMENTS IN CURE RATES. OVER THESE YEARS. AND I THINK THAT THE MOST IMPORTANT POINT I WOULD LIKE TO MAKE IN THIS INTRODUCTION IS EVEN THOUGH WE HAVE GOTTEN TO A POINT WHERE TWO-THIRDS OF CHILDREN OR MORE CAN BE CURED OF CHILDHOOD CANCER, THE WAY WE'RE DOING IT IS UNACCEPTABLE. SO THE WAY YOU READ THIS GRAPH IS THIS IS THE CUMULATIVE INCIDENCE OR FREQUENCY WITH WHICH SEVERE SIDE EFFECTS SHOW UP IN SURVIVORS OF CHILDHOOD CANCER, THIS IS YEARS THAT GOT CUT OFF BUT YEARS AFTER PLEATING CANCER THERAPY. WE THOUGHT BACK IN THE DAY THERE'S SIDE EFFECTS EARLY ON BUT THAT IT WOULD PLATEAU. SURVIVORS OF CHILDHOOD CANCER ARE SCARRED FOR LIFE AT LEAST THE WAY WE CURRENTLY TREAT CHILDHOOD CANCER. SO THERE ARE A SUBSET OF CHILDREN WITH SEVERE TOXICITIES THAT ARE LIFE THREATENING. SO ALMOST ALL CHILDREN GET SOME SIDE EFFECTS OF THERAPY, THAT SURVIVE TO ADULTHOOD. MANY HAVE CONGESTIVE HEART FAILURE T DEVELOPMENT OF A SECOND MALIGNANCY, OTHER SEVERE SIDE EFFECTS SO CLEARLY BECAUSE OF THE PLATEAUED CURE RATES AS WELL AS THE COST OF SURVIVING CHILDHOOD CANCER, WE NEED TO RE-ENGINEER WHAT WE'RE DOING. SO I'M IN THE BASIC SCIENTIST, I HAVE BEEN INVOLVED IN CANCER GENETICS AND GENOMICS. I WILL ROLE THROUGH TITLES OF MANUSCRIPTS HERE. THE POINT IS IN THE LAST TWO OR THREE YEARS, THERE'S BEEN A IMUNPRECEDENTED NUMBER OF PUBLICATIONS IN VERY HIGH PROFILE JOURNALS FROM COLLABORATIVE PEDIATRIC ONCOLOGISTS TRYING TO UNDERSTAND BASIC MECHANISMS OF CHILDHOOD CANCER AND DESCRIBE PRECISE GENETIC LEVEL ALL MUTATIONS THAT ARE OCCURRING IN A WHOLE VARIETY OF CHILDHOOD CANCERS. WHAT WE HAVE COME UP WITH, THIS IS A MIXTURE OF CHILDHOOD AND ADULT CANCERS, A COMPENDIUM OF BEING ABLE TO QUANTIFY THE NUMBER OF MUTATIONS IN THESE DISEASES TRYING TO UNDERSTAND HOW THESE MUTATIONS ALLOW CANCERS TO ARISE IN FIRST PLACE TO PROGRESS TO DEFINE THE TYPE OF CANCER WE SEE IN THE CLINIC, MATCH MUTATIONS TO RATIONAL THERAPIES. DESCRIPTION AND NUMBER OF DISCOVERIES IN CHILDHOOD CANCER IS AMAZING. ONE FACT OF LIFE, I ALLUDED TO THIS IN THE BEGINNING IS CHILDHOOD CANCERS TEND TO HAVE A LOWER NUMBER OF THESE GENETIC CHANGES COMPARED TO ADULT CANCER. THIS MAKES PERFECT SENSE. WAY OVER HERE IS MELANOMA WHERE WE KNOW THAT THE UV EXPOSURE WHICH CAUSES MUTATIONS IS THE MOST FREQUENTLY MUTATED. A LOT OF THESE MUTATIONS ARE NOISE. SO THESE MUTATIONS ARE TRULY IN THE PEDIATRIC CANCERS WE THINK HAVE A VERY, VERY IMPORTANT ROLE IN THE DEVELOPMENT OF THE DISEASE IN THE PROGRESSION OF THE DISEASE. WE'RE ALSO IN THIS AMAZING AREA OF UNPRECEDENTED THERAPEUTIC ADVANCEMENTS. BUT THESE ARE TWO EXAMPLEPS OF IMMUNOTHERAPEUTIC RESULTS IN CLINICAL TRIALS, THE FIRST DISEASE NEUROBLASTOMA USING AN ANTIBODY, MALCOLM WILL TALK MORE ABOUT THIS, TO TRY TO PREVENT RELAPSE IN CHILDREN WHO ACHIEVED REMISSION WITH CHEMOTHERAPY AND RADIATION THERAPY. IMPROVE SURVIVAL RATES, OR AT LEAST RELAPSE FREE RATES BY 20% WHICH IS A MAJOR ADVANCEMENT IN THE DISEASE THAT'S BEEN RESISTANT TO IMPROVEMENTS IN CANCER. AND THERAPY. THIS IS AN EXAMPLE FROM A PAPER LAST YEAR IN THE NEW ENGLAND JOURNAL USING A ENGINEER T-CELL SO TURNING ON THE IMMUNE SYSTEM BY RE-ENGINEERING A T-CELL, THESE ARE ALL THE BAD LEUKEMIA CELLS IN THIS FLOW CYTOMETRY PLOT. A SINGLE INJECTION OF THIS MADE CELLS GO AWAY, THIS CHILD IS NOW 18 MONTHS OUT AND WAS CURED OF HER HIGHLY REFRACTORY LEUKEMIA WITH A SINGLE INFUSION OF ENGINEER T-CELLS SO THESE ARE UNPRECEDENTED ADVANCEMENTS AND I CAN SPEAK TO THE EXCITEMENT IN THE FIELD. SO FOR THE REST OF THE TIME I'M GOING TO GO THROUGH THE SIX QUESTIONS POSED TO ME. AGAIN, GIVE YOU MY ADMITTEDLY BIASED VIEWS AS SOMEONE IN THE EXTRAMURAL PROGRAM WHO HAS BEEN IN THER RA OF DOING BASIC RESEARCH AND TRANSLATING THAT TO THE CLINIC. I DO SEEK PATIENTS. I DO SEE MANY PATIENTS WITH A SPECIALTY IN NEUROBLASTOMA SO I SEE ISSUES FROM ALL THOSE ENDS, AND WILL GIVE YOU MY OPINIONS SO THIS ONE IS EASY. I DON'T THINK WE WOULD BE HERE IN THE ANSWER WAS -- IF THE ANSWER WAS YES SO WE ARE ALL HERE TODAY AND IN OUR LABORATORIES AN CLINICS TRYING TO FIGURE OUT SMARTER WAYS, MORE EFFICIENT WAYS TO DEVELOP PEDIATRIC TREATMENTS. THERE ARE THINGS WORKING AND THINGS YOUR PERCEIVE WORKING NOT ON THIS LIST, PLEASE, THIS IS A MY VIEW OF THE MORE IMPORTANT THINGS THAT ARE FRONT AND CENTER OF MY MIND AT THIS POINT IN TIME. AS THE FEDERAL FUNDING FOR ALL THE WORK WE'RE DOING, THAT'S BEEN RESTRICTED, IT'S BEEN WONDERFUL TO SEE HOW PHILANTHROPIC ORGANIZATIONS MANY WHOM ARE HERE, AND INDUSTRY HAVE TEN STEPPED TO THE PLATE TO FUND BASIC RESEARCH. MY LABORATORY USED TO BE 1 NEEDS TO BE 100% FUNDED. RIGHT NOW IT'S 40% FUN AND REST IS SPLIT BETWEEN PHILANTHROPY AND INDUSTRY FOR PRE-CLINICAL WORK. THAT'S RELATIVELY COMMON ACROSS THE FIELD. CLEARLY AS WE CAN SEE TODAY THE ADVOCACY COMMUNITY IS HIGHLY ENGAGED. AND LOOKING FOR WAYS TO WORK WITH THE SCIENTIFIC COMMUNITY TO MAKE A DIFFERENCE. AMONG THE INVESTIGATORS AS WITNESSED BY THOSE, MANY SHOWED UP EACH WHICH HAD 30, 40, 50 AUTHORS, THE COLLABORATIVE SPIRIT TO DO WORK TOGETHER TO MAKE A DIFFERENCE, SOMETHING I THINK IS ALWAYS COMMON TO PEDIATRICIAN. ENRICHED ALL TIME HIGH AT LEAST IN MY PERSPECTIVE. THERE ARE OBVIOUSLY ISSUES. AND THIS IS PROBABLY A SHORT LIST OF WHAT WE'LL GET INTO THESE ISSUES AS WE GO THROUGH THE PARTS OF THE TALK AND MALCOLM AND LEE'S. ONE TALK ALL DAY ABOUT FUNDING AND THE ISSUES WITHIN NIH FUNDING BUT ONE POINT I'M SURE CLEAR TO MANY PEOPLE IN THE ROOM, THE BIGGEST CONCERN I HAVE IS WE'RE LOUING THE NEXT GENERATION OF PHYSICIAN SCIENTISTS. CLEAR PEOPLE LIKE ME GET THROUGH THE TIGHT BUDGET TIMES BUT YOUNG INVESTIGATORS WHO ARE NOT GETTING THEIR INITIAL K AWARDS OR INITIAL R AWARDS OR CAN'T RENEW INITIAL GRANTS ARE GETTING DISCOURAGED. WE SEE THIS ALL THE TIME. PHILANTHROPY HELPED FILL THE GAP BUT THIS IS A REAL RISK. PEDIATRIC ONCOLOGY, THERE'S A SHIFT IN THIS, WE REMAIN RELIANT ON INDUSTRY. THERE I'LL SHOW YOU ONE EXAMPLE HOW WE'RE TRYING TO APPROACH THIS BUT THIS IS CLEARLY AN ISSUE THAT WE CAN WORK A LONG TIME ON A TARGET, POTENTIAL TARGET DRUG MATCH. IT HAPPENED SEVERAL TIME WHERE IS THAT DRUG GOES AWAY AND THERE'S NO EASY WAY FOR US AS A COMMUNITY TO RESPOND AND DEVELOP. THERE ARE CLEARLY EXCEPTIONS. JUST IN GENERAL, THERE'S OBVIOUS ISSUE OF RISK AVERSION HURTING VULNERABLE POPULATION OF CHILDREN AND I THINK THAT WE HAVE -- ALWAYS HAVE THIS BALANCE HOW WE CAN BE AGGRESSIVE, CHILDREN WHO HAVE RELAXED REFRACTORY CANCER MOVE QUICKLY AS POSSIBLE AND HANDLE RISK OF DOING INNOVATIVE CLINICAL RESEARCH IN A TIMELY WAY. BRIEFLY FOR THIS ONE, THE SECOND QUESTION, WHAT EXTENT EXPERIENCE WITH NEW INVESTIGATIONAL PRODUCT IS REQUIRED BEFORE IT THIS WORD REQUIRED, I THINK THAT OPTIMALLY THERE'S THE COMPLETION OF A PHASE 1 TRIAL, THERE'S SAFETY DATA, THERE'S A RECOMMENDED PHASE 2 DOSE, THAT'S GREAT WHEN THAT HAPPENS, IT OFTEN DOES HAPPEN. IF WE'RE SUCCESSFUL DEVELOPING TARGETS AND WE HAVE SOME EXAMPLES OF THIS, THERE ARE EXCEPTIONS WITH PEDIATRIC INDICATIONS. -- IF THIS FIRST IN HUMAN STUDY, WHAT DO YOU DO IF THERE'S NO REASON TO GIVE TO THE ADULT, IT NEEDS TO BE FIRST IN CHILD STUDY, HOW WE'RE GOING TO DO THAT. WE'RE STRUGGLING WITH THIS WITH PROGRAMS WE'RE DEVELOPING. THE ADDITIONAL CHALLENGE, THE FIELD AS A WHOLE HAS NOT DEALT WITH THIS, WE MAKE PROGRESS WITH TARGETED THERAPIES WE HAVE TO QUICKLY MOVE TO NOVEL COMBINATIONS. DO WE NEED TO TEST EACH COMBINATION IN ADULTS BEFORE THEY COME TO KIDS. IF THAT'S THE CASE WE'RE GOING TO BE VERY SLOW IN OUR CLINICAL DEVELOPMENT. THIRD QUESTION HOW SPECIFICALLY ARE RESEARCHERS TRANSLATING ADVANCES TO OUTCOMES FOR CHILDREN. TWO EXAMPLES FROM MY OWN PROGRAM, CLEARLY EMPHASIS ON PRECISION MEDICINE APPROACHES. THAT'S THE EXAMPLE NOT FROM MY GROUP PHILADELPHIA CHROMOSOME AOL AND PERFECT MATCH HEMATOANYBODY THAT'S CHANGED DRAMATICALLY FROM A DISEASE UNIFORMLY FATAL TO ONE THAT CAN BE CURED. MOST OF THE TIME. THE MUTATIONS ARE TRANSLOCATIONS IN THE GENE IN LARGE CELL LYMPHOMAS AND NEUROBLASTOMAS AN SARCOMAS CHANGED THE WAY WE THINK ABOUT THOSE. WHERE WE NEED TO BE, WE'RE WELL INTO THE DEVELOPMENT OF WHAT WE'RE CALLING A MASTER POLYPROTOCOL, THE CLINICAL TRIAL CONCEPT THAT IS BROUGHT FORWARD IN ADULT CANCER ESPECIALLY LUNG CANCER THAT IF ONE HAS ENOUGH ROBUST BIOMARKERS OF WHAT GENETIC CHANGE IN TUMOR CELL PREDICT FOR RESPONSE TO HAVE A CLINICAL TRIAL, WHERE YOU CAN ROLE IN DIFFERENT MATCHES OF BIOMARKERS AND POTENTIAL DRUGS TO TREAT THOSE WITH THE WHOLE GOAL OF TRYING TO MEASURE RESPONSE RATE RELATIVELY SMALL COHORTS OF PATIENTS IN VERY EFFICIENT WAY. THIS IS A LARGE EFFORT. THE SECOND EFFORT AGAIN SHOWS HOW ADVOCACY MAKES SUCH A DIFFERENT DIFFERENCE, I HAVE THE PLEASURE OF CO-CHAIRING WITH CRYSTAL MAY GAL AT THE ONCOLOGY BRANCH, PEDIATRIC CANCER IMMUNOGENOMICS DREAM TEAM, A PARTNERSHIP BETWEEN STAND UP TO CANCER ORGANIZATION AND BALL DISTRICTS FOUNDATION THAT FUNDED THIS. THIS IS A MAJOR EFFORT TO DEVELOP DRUGS BY OURSELVES. IN ACADEMIA, TO TARGET IMMUNOTHERAPEUTIC PROTEIN OR IMMUNE TARGETS SPECIFIC TO PEDIATRIC CANCER CELLS. SO THIS CARTOON SHOW IT IS WAY WE USED TO THINK, THERE -- HERE IS YOUR CANCER CELL, THERE'S THINGS ON THE SURFACE OF THE CANCER CELL LIKE ALK AND OTHER THINGS THAT CAN BE MUTATED. WE HAVE BEEN TARGETING THESE WITH SMALL MOLECULES BUT ALSO COME IN WITH T-CELLS OR ANTIBODIES OR A VARIETY OF DIFFERENT IMMUNE TARGETS. THERE'S WAY TO DO THIS ON AN INDIVIDUALIZED LEVEL WHICH IS A FUTURE GOAL BUT THE GOAL OVER THE NEXT FOUR YEARS IS TO DEVELOP THESE TYPE OF DRUGS IN ACADEMIA AGAINST THESE SORTS OF MOLECULES THAT ARE DIFFERENTIALLY ON THE SURFACE OF PEDIATRIC CANCER CELLS AND NOT NORMAL DEVELOPING CHILDHOOD TISSUES, AND MAY OR MAY NOT BE ADULT MALIGNANCIES. FOURTH QUESTION WE WERE ASKED, WHAT IS WORKING, WHAT ARE THE CHALLENGES IN THE PRE-CLINICAL ARENA. MALCOLM WILL SPEAK MORE TO THIS SO I'LL SAY BRIEFLY, I HAVE BEEN INVOLVED WITH THE THERAPEUTICALLY APPLICABLE RESEARCH EFFECTIVE TREATMENT, THIS IS THE NCI EFFORT TO DEFINE MUTATIONS AS I SHOWED YOU IN THE BEGINNING OF THE TALK IN PEDIATRIC CANCER, THAT'S CERTAINLY WORKING. WE DEVELOPED METHODS TO SCREEN DRUGS IN THE PIPELINE THROUGH THE PEDIATRIC PRE-CLINICAL TESTING PROGRAM NOW TEN YEARS IN. I THINK I'M NOT GOING TO SAY MORE ABOUT IT, AT THIS POINT BECAUSE I THINK MALCOLM WILL SPEAK TO IT. AS A COMMUNITY, WE STEADILY IMPROVED COLLECTION PRE-CLINICAL MODELS. THERE'S A LOT OF DEBATE IN THE CANCER COMMUNITY WHETHER THIS MOUSE OR THAT MOUSE OR ZEBRAFISH WHAT WE BELIEVE IS THERE'S NO ONE MODEL THAT FITS WHAT YOU NEED FOR DRUG DEVELOPMENT, YOU HAVE TO HAVE A DIVERSIFICATION, YOU HAVE TO BE SMART ENOUGH TO KNOW WHICH OF THESE MODELS MAKES SENSE FOR THE TYPE OF PRE-CLINICAL PROGRAM YOU HAVE. WHAT ELSE IS WORKING SOMETHING THAT'S BEEN AS I SAID AT LEAST FROM MY PERSPECTIVE INTEREST ON THE INDUSTRY SIDE, TO COLLABORATE, IF THE SCIENCE IS THERE TO SUPPORT THE TYPE OF INDUSTRY COLLABORATIONS. THE CHALLENGES, THIS GETS TALKED ABOUT A LOT IF YOU LOOK AT CHILDHOOD CANCERS COMPARED TO ADULT, THERE'S LESS MUTATIONS, BUT ONE ANOTHER VERY IMPORTANT POINTS IS ALL THE DATA WE HAVE NOW IN CHILDHOOD CANCERS ARE ON TUMORS WHEN THE PATIENT SHOWS UP ORIGINALLY WITH -- IN THE CLINIC WITH THE DISEASE AT DIAGNOSIS. WE ALREADY KNOW CANCER CELLS EVOLVE QUITE RAPIDLY UNDER THE SELECTIVE PRESSURE OF THERAPY AND CHANGE DRAMATICALLY. WHAT THE PEDIATRIC CANCER COMMUNITY STRUGGLED WITH IS ACCESS TO TUMOR CELLS AT RELAPSE OR EVEN AUTOPSY. THIS IS SO IMPORTANT BECAUSE WHEN CHILD ENTERS A PHASE 1 TRIAL THEIR CANCER IS ALREADY MUTATED. IT'S ONLY A SHELL OF WHAT IT WAS AT DIAGNOSIS. AS WE HAVE BEGUN TO DO MORE OF THIS, WE FIND MORE DRUG TARGETS AVAILABLE, IDENTIFIABLE IN THOSE RELAPSE SAMPLES. THIS HAS TO BE A MAJOR FOCUS OF OUR WORK MOVING FORWARD. THERE ARE ETHICAL ISSUES HERE ABOUT THAT I'M COMFORTABLE WITH AND WE CAN DOES CUSS WHEN AND HOW AND ARE WE IN EQUIPOISE. TIDE TO THIS IS THAT WE TIED TO THIS IS WE NEED TO HAVE BETTER MARKERS WHETHER OR NOT A DRUG WILL WORK. I THINK WE HAVE A FEW OF THOSE BUT THIS TO ME, IT SHOULDN'T BE -- WE HAVE TO GET AWAY FROM -- THERE'S A LIST OF TRIALS AVAILABLE WHENEVER IS OPEN THE CHILD GOES ON THERE HAS TO BE A RATIONAL ASSIGNMENT BASED UPON TUMOR GENETICS. WE AS A COMMUNITY I THINK LACK A COMPREHENSIVE STRATEGY TO SCREEN FOR NEW DRUGS ESPECIALLY NEW DRUG COMBINATIONS. IT'S DONE IN A HELL TRISCELE SORT OF WAY. AND MAYBE THIS IS THE SORT OF THING THAT'S WHY ACADEMIA IS GOOD AND THERE SHOULD BE DIVERSIFICATION. BUT I THINK ESPECIALLY FOCUSING ON DRUG COMBINATIONS, PEDIATRIC CANCER COMMUNITY CAN COME TOGETHER. TIED TO THIS IS DEFINING NOT JUST ONE PLUS ONE EQUALS TWO BUT ONE PLUS ONE EQUALS 4 SYNERGISTIC INTERACTIONS, THINGS THAT MAKE POTENTIAL DIFFERENCE. HAPPY TO SAY WE DO HAVE EXAMPLES AT LEAST IN THE DISEASE NEUROBLASTOMA. I WAS ASKED, WE WERE ASKED WHAT IS WORKING AND WHAT ARE THE CHALLENGES IN CLINICAL RESEARCH. I THINK ADULT CANCERS ARE BECOMING COMPARTMENTALIZED NOT TO THE POINT WHERE THE SUBSETS ARE SMALL AS PEDIATRIC CANCER COMMUNITY BUT I THINK WHEN YOU'RE TALKING ABOUT GENOMIC ALTERATIONS AND SUBSET OF LUNG CANCERS THAT ARE 3 OR 4%, IT'S STILL A LARGE NUMBER OF INDIVIDUALS BUT IT IS CHALLENGED THE PHARMACEUTICAL INDUSTRY TO THINK DIFFERENTLY ABOUT HOW THEY DEVELOP DRUGS IN RARE SUBSETS. I THINK THAT'S WHAT WE HAVE BEEN DOING AT PEDIATRICS FOR A VERY LONG TIME SO THIS IS IMPORTANT. (INAUDIBLE) WILL SPEAK LATER, THE FORMER AND CURRENT CHAIR, FROM MY PERSPECTIVE, IT'S THE WORLD'S BEST ORGANIZATION TO DO THE PIVOTAL TRIALS, PHASE 2 PHASE 3 TRIALS IN ORPHAN DISEASES ANYWHERE IN THE WORLD. WE HAVE THAT AS AN ADVANTAGE. WE ARE SUPPOSED TO HAVE A DRUG DEVELOPMENT PIPELINE, IT IS TRICKLING. THAT MIGHT BE AN OVERESTIMATE. AS A CLINICIAN WHO SEES THESE CHILDREN, THREE CONSULTS YESTERDAY FOR CHILDREN WHO HAVE RELAPSE DISEASE, THERE'S NOTHING OPEN. THERE'S NOT A SINGLE PHASE 1 TRIAL THAT I CAN ENROLL THIS CHILD ON YESTERDAY BECAUSE THERE'S NOTHING OPEN RIGHT NOW. SO CAME UP WITH STRATEGIES BUT IT'S A FINGER IN THE DIKE. AS MENTIONED EARLIER WE GOT TO GET TO THE POINT NOT JUST OPEN BUT HAVE A PANEL WITH STUDIES OPEN WHERE THERE'S A RATIONAL ASSIGNMENT. I THINK THIS ISSUE I ADDRESSED, IN MY OPINION IN CERTAIN DISEASES, NEUROPALACE TOE MARKS MEDULLAR PALACE TOE MA, THE RESULT OF A BIOPSY AT TIME OF RELAPSE OR PROGRESSION, FIRST THE BIOPSY CAN BE DONE IN A SAFE WAY DESPITE WHERE IT IS THE INTERVENTIONAL RADIOLOGISTS AND PEDIATRICS ARE EXTRAORDINARILY CLINICAL LENTED. AND THERE'S -- TALENTED. SO I BELIEVE WE ARE EQUIPOISE AND NEED TO DO BIOPSIES AT RELAPSE PROGRESSION. BUT THAT'S NOT A GENERALLY AGREED UPON STATEMENT. WE STILL LACK ABILITY IN OUR CLINICAL TRIALS TO DETERMINE WHY A DRUG WORKS WHEN IT WORKS, OR WHY A DRUG FAILS WHEN IT FAILS. WE DON'T HAVE GOOD-BYE MARKERS IN SERUM, WE DON'T UNDERSTAND WHY RESISTANCE OCCURS. IN PATIENTS. THAT'S SOMETHING WE NEED TO APPROACH AS A COMMUNITY. SO WRAPPING UP WITH THE SIX AND FINAL QUESTION, WHAT IS NCI INVESTMENT CANCER RESEARCH AND HOW IS NCI WORKING WITH INDUSTRY, I DIDN'T FEEL THAT I WAS -- I THINK OTHERS CAN SPEAK TO THIS BETTER THAN ME. I DO BELIEVE AS SOMEBODY WHO WRITES NIH GRANTS, IT'S MY IMPRESSION THAT SPEAKING TO THE PROBLEM OF CHILDHOOD CANCER, THE IMPACT RESEARCH COULD MAKE IF SUCCESSFUL IN TERMS OF TRANSLATABILITY AND CLINICAL IMPACT, THAT IS VERY VALUED IN NIH STUDY SECTIONS, THESE ARE THE PROJECTS THAT I BELIEVE ARE GETTING FUNDED THESE DAYS AND I THINK THAT'S IMPORTANT. I THINK WE CAN REALLY WORK WITH THE NCI TO HAVE MORE PEDIATRIC CANCER SPECIFIC, REQUEST FOR APPLICATIONS OR PROJECTS THAT ARE DESIGNED FOR PEDIATRIC CANCER COMMUNITY. I'M NOT ONE OF THESE INDIVIDUALS WHO THINK THERE SHOULD BE A CUT OUT OR A CERTAIN SLICE OF THE PIE, I THINK WE NEED TO STEP UP TO THE PLATE WITH THE IDEAS AND I THINK WE CAN DO THAT WITH -- IF WE DEFINE THE RIGHT QUESTIONS WITH THE NCI. IN MINIMIZING BARRIERS, IN THE PRE-CLINICAL TESTING PROGRAM IS HOW TO ENGAGE INDUSTRY EARLY ON IN DEVELOPING THE PRE-CLINICAL DATA SO THAT WE HAVE THAT COLLABORATION AS WE MOVE FORWARD. I THINK THAT'S A GREAT EXAMPLE OF HOW WE SHOULD DO THINGS. IN MY OPINION THERE'S NEVER A MORE EXCITING TIME IN AT THIS COVERRYING CANCER ETIOLOGY INTERVENTION AND EVOLUTION. IT'S A HEADING TIME IN TERMS OF DISCOVERY IN THINGS WE LEARN AND HOW QUICKLY WE'RE LEARNING. BUT ON THE OTHER HAND THERE'S NEVER BEEN A MORE FRUSTRATING TIME TO BE A PHYSICIAN SCIENTIST TRYING TO GET THIS INTO THE CLINIC OR ONE WHO IS TAKING CARE OF CHILDREN WITH REFRACTORY CANCER AND FACED EVERY DAY WITH THE BARRIER OF LOOKING A PARENT IN THE EYE AND SAYING THERE'S NOTHING AVAILABLE TODAY. SO WE'LL USE (INDISCERNIBLE) WE HAVE BEEN DOING IT FOR THE LAST 20 YEARS. THANK YOU FOR YOUR ATTENTION. >> DR. MARIS, THANK YOU VERY MUCH. WHAT I WOULD LIKE TO DO IS OFFER THE OPPORTUNITY FOR A COUPLE OF QUESTIONS BUT TO HAVE THOSE QUESTIONS PHRASED HOW THEY'RE SPECIFIC TO WHAT WE HAVE SEEN BECAUSE WE'RE GOING TO HAVE AMPLIFIED PRESENTATIONS FROM TWO NCI FOLKS COMING UP. I WOULD LIKE TO HAVE QUESTIONING AT THE END OF THAT WHERE WE CAN HAVE THE WHOLE GROUP PARTICIPATE. SO IF THERE ARE QUESTIONS FOR DR. MARIS BASED ON THE PRESENTATION, I ENTERTAIN THEM. ONE IN THE BACK CORNER, DO WE HAVE A MICROPHONE? >> JOHN, THANKS FOR THAT PRESENTATION. ONE THING YOU SAID EARLY ON IN SIDE EFFECT CHART ABOUT 1 THROUGH 5 AND GRADE 3 THROUGH 5, AFFECTING THE SURVIVOR POPULATION, IS THERE ANYTHING IN YOUR EXPERIENCE THAT THE DRUG DEVELOPMENT NEEDS TO DO SPECIFICALLY TARGETED STUDY, THAT MARCH COMPONENT OF SO MANY PERCENTAGE OF KIDS SURVIVING WITH THE NEGATIVE SIDE EFFECTS? >> I THINK THAT -- THANK YOU FOR THE QUESTION. THE PROMISE OF SO CALLED TARGETED THERAPY IS TO BE MORE TUMOR SPECIFIC AND LESS EFFECT ON DEVELOPING CHILD. THESE TARGETED AGENTS HAVE POTENTIAL SIDE EFFECTS AND IT DEPENDS HOW TARGETD THEY ARE. SO CLEARLY, TARGETED THEY ARE, WE HAVE A LONG WAY TO GO TO GET TO A COMPLETELY NON-TOXIC THERAPY. THIS DRUG (INDISCERNIBLE) IS A GREAT EXAMPLE OF ONE THAT SHORT OF MEETS -- MOVES TOWARDS THAT BECAUSE THIS PROTEIN ALK IS NOT EXPRESSED ON NORMAL CELLS AFTER DEVELOPMENT SO THAT THE SIDE EFFECT PROFILE IS VERY, VERY LOW. AND THERE IS SOME BUT IT'S -- IT AT LEAST GIVES SOME HOPE THIS IDEA OF TARGETED THERAPY DOES HAVE REALISTIC PROMISE. >> THANK YOU, EXCELLENT PRESENTATION. ONE THING WE HAVE HEARD IS CHILDREN'S CANCER CLINICAL TRIALS CHILDREN ENROLLED IN CLINICAL TRIALS HAS BEEN THE MODEL HOW THE ENTIRE SCIENTIFIC ENTERPRISE SHOULD OPERATE IN TERMS OF ADULT POPULATION, GET PEOPLE ACCRUED. WHAT STRUCK ME, YOU TALK ABOUT YOU COULD BE FIND CLINICAL TRIALS FOR SOME OF YOUR CHILDREN. SO THAT'S VERY CONCERNING. DOES THAT LINE UP WITH THE FIRST STATEMENT ABOUT 80% OF ALL CHILDREN ENROLLED IN CLINICAL TRIALS, IS THAT ACCURATE? Q. JOHN, LET ME TRY TO ADDRESS THAT BRIEFLY. AND WE'LL TALK MORE ABOUT THIS. , YES, IT'S BEEN A MODEL. WHEN WE TALK ABOUT CHILDREN ENROLLED, NEWLY DIAGNOSED WITH CANCER, WE STILL ARE A MODEL ORGANIZATION. WE HAVE CHANGED THINGS, WE TRIED TO GET MORE FOCUSED, IT USED TO BE ANY CHILD WHO SHOWED UP WOULD END UP ON A CLINICAL TRIAL AT DIAGNOSIS. BUT AS WE'VE -- THAT FIRST BAR CHART I SHOWED, IN CERTAIN DISEASES THE CURE RATES ARE REALLY OUTSTANDING, PERHAPS WE DON'T NEED TO PUT THE RESOURCES IN CLINICAL TRIALS THERE SO WE HAVE NOT HAD CLINICAL TRIALS FOR LOW RISK TUMOR OR LOW RISK NEUROBLASTOMA, NOT AS FREQUENTLY. SO WE DON'T NEED TO MAINTAIN THAT 80%, WE NEED TO GET KIDS ON CLINICAL TRIALS WHO HAVE MORE AGGRESSIVE DISEASE AND BE VERY GOOD THERE. IT'S VERY DIFFERENT IN THE -- FOR CHILDREN WITH RELAPSE REFRACTORY DISEASE, THERE'S UNMET NEED, WE HAVE HAD A HARD TIME IN THE LAST FEW YEARS, HAVING A PORTFOLIO OF CREATIVE PHASE 1 OR 2 TRIALS AVAILABLE TO THE COMMUNITY. IT'S A HUGE PROBLEM. THAT IS WHY WE'RE HERE. >> (INAUDIBLE) (OFF MIC) >> I'M INTERESTED WHEN YOU SAY THE T-CELL THERAPY IS EXCITING. WE'RE HELPING TO WRITE A LAB AT MEMORIAL SLOAN I GATHER IS NOW FOCUSED ON LEUKEMIA AND LYMPHOMAS FOR CHILDREN AN YOUNG ADULTS, HAVE YOU SEEN ANY SUCCESS IN T-CELL THERAPY BEYOND LEUKEMIAS AN LIMB LYMPHOMAS? >> GREAT QUESTION, YES. THERE'S ENORMOUS AMOUNT OF ABOUT T-CELL THERAPIES. OUR CLINICAL TRIAL WE HAVE ENROLLED ABOUT 28 PATIENTS WITH REFRACTORY LEUKEMIA. AND HAVE COMPLETE RESPONSE RATES OF 86% NOT UNHEARD OF EARLY RESULT. THE WHOLE PURPOSE OF OUR DREAM TEAM GRANT IF YOU WILL IS TO TAKE THAT SUCCESS INTO THE SOLID TUMOR WORLD. ZOAL TUMORS HAVE BEEN MUCH MORE DIFFICULT FOR A VARIETY OF REASONS BUT THAT'S WHAT WE ARE TRYING TO DO, COLLABORATION OTHER THE NEXT FOUR YEARS TO MEASURE LYMPHOBLASTOMAS AND DIFFUSE INTRINSIC GLIOMASS, THE HIGH RISK SARCOMAS, HOW DO WE GET THESE THERAPIES TO WORK IN THOSE DISEASES. >> MAYBE I CAN ANSWER A LITTLE BIT MORE DIRECTLY. SO THERE IS AN EXPRESS PROTEIN CALLED A CANCER TESTES ANTIGEN IN A SARCOMA CALLED SYNOVIAL SARCOMA. IT'S A RARE SARCOMA THAT OKAY CAN CURS IN BOTH CHILDREN, YOUNG ADULTS AND ACTUALLY ADULTS AS WELL. SO EXPRESSES ANTIGEN, WE HAVE LEARNED TO MAKE A T-CELL THAT WE PUT A -- WE PUT A -- THAT RECOGNIZES WE PUT THE RECEPTOR THAT RECOGNIZES THAT, IT'S CALLED NYESO 1. WE HAVE SEEN OVER 50% RESPONSE RATE. IN PATIENTS WITH SYNOVIAL SARCOMA THAT GET THE ENGINEERED T-CELL, THEIR OWN T-CELL WE PUT IN A RECEPTOR. THE PROBLEM IS SO FAR, THEY RESPOND FOR A PERIOD OF TIME, LIKE ALL MONOTHERAPIES THEY RECUR. BUT THE FACT WE HAVE SEEN IN SOLID TUMORS MAKES US REALIZE IT WILL WORK. WE NEED THE RIGHT ANTIGENS THAT THE TUMOR NEEDS. THEN WE NEED TO FIND SOMETHING ELSE AND THERE ARE SOME OF THE REAL EXCITEMENT IN THE FIELD ONCOLOGY THE LAST YEAR HAS BEEN THE SO CALLED CHECK POINT INHIBITORS. THEY ARE SIGNALING PATHWAYS THAT TURN OFF THE IMMUNE RESPONSE. BECAUSE WHEN WE'RE HEALTHY, WE DEVELOP AN IMMUNE RESPONSE TO BACTERIA, YOU WANT TO TURN OFF THE IMMUNE RESPONSE WHEN THE BACTERIA GOES AWAY. SO NOW WE HAVE LEARNED HOW TO MANIPULATE THAT TO MAYBE KEEP THAT IMMUNE RESPONSE GOING LONGER IN THIS MANIPULATED ENVIRONMENT. SO WE HAVE YET TO GET ACCESS TO THESE DRUGS, WE'RE JUST ABOUT TO OPEN A PEDIATRIC STUDY, SO THERE WAS ENORMOUS PROMISE AND DEMONSTRATED ACTIVITY IN SOLID TUMORS. WE JUST HAVE TO FIND THE RIGHT TARGETS. (OFF MIC) >> THE ANSWER IS YES. THE PROJECT WE HAVE IS INSTITUTION, THE PLACES YOU MENTIONED, YES, THE HOSPITALS ARE WORKING TOGETHER ON. THIS ONE OF THE GOALS IS TO GET THIS OUT OF A NICHE, YOU HAVE TO COME TO ONE INSTITUTE AND HE CAN PORT THIS TYPE OF THERAPY -- EXPORT THIS TYPE OF THERAPY. >> THANK Y ALL FOR THE QUESTIONS. DR. MARIS THANK YOU FOR THAT PRESENTATION. I WOULD LIKE TO MOVE TO DR. SMITH NOW. WE WILL HAVE TIME NOT ONLY AFTER DR. SMITH'S TALK TO ASK SPECIFIC QUESTIONS BUT TO ENGAGE THE GROUP. >> IT IS A REAL PLEASURE TO BE HERE TODAY AND TO SEE A NUMBER OF FAMILIAR FACES AND BECOME ACQUAINTED WITH NEW FACES, HONOR TO BE ON THE JOB WITH JOHN AND THE PANEL. IT'S ALL ON THE PERSON SPECKTIVE OF STATE OF PEDIATRIC CANCER RESEARCH. FROM NCI PERSPECTIVE, THE NCI PART OF NCI THAT SUPPORTS EXTERNAL RESEARCH T RESEARCH THAT'S DONE THROUGHOUT THE COUNTRY. UNLIKE JOHN I DID GET MY SLIDES IN EARLY THIS WEEK. BUT LIKE JOHN I CHANGED THEM THIS MORNING. I DO APPRECIATE THE STAFF GETTING COPIES OF MY CURRENT SLIDES. SO YOU DO HAVE COPIES OF THEM. NCI TRIES TO BE A CONTRIBUTOR IN ALL SECTORS OF CHILDHOOD CANCER THERAPY -- THERAPEUTIC RESEARCH FROM THE INITIAL DISCOVERY RESEARCH AND THE TARGET DISCOVERY PROGRAM THROUGH PRE-CLINICAL TESTING PHASE 1 AND DEFINITIVE TRIALS. THESE ARE JUST LISTED SOME OF THE PROGRAMS HERE ON THIS SLIDE THROUGH THE PRE-CLINICAL TESTING PROGRAM, THE PHASE 1 EARLY PHASE TRIALS CONSORTIA LIKE THE DOJ PHASE 1, PEDIATRIC BRAIN TUMOR CONSORTIUM, THE NCI INTRAMURAL RESEARCH PROGRAM, CHILDHOOD CANCER SURVIVORSHIP STUDY, TRACKING AS JOHN MENTIONED, THE RESEARCH FROM THAT STUDY, TRACKING WHAT ARE THE CHALLENGES SURVIVORS FACE AND WHAT ARE THE ISSUES THAT DIMINISH THEIR QUALITY OF LIFE. THEN LARGE NUMBER OF INVESTIGATOR INITIATED RESEARCH PROJECTS. ONE POINT, SINCE ALL THIS AROUND $200 MILLION OR A LITTLE OVER $200 MILLION, THE ONE POINT TO MAKE ABOUT THIS IS BASIC RESEARCH THAT WE'RE DOING TODAY NOT CODED TO CHILDHOOD CANCER, BUT THAT IS THE RESEARCH THAT WE'LL NEED FOR CURING THE CHILDREN WITH USINGS SARCOMA OR SARCOMA NOT CURED TODAY. TO GIVE AN EXAMPLE, EARLIER THIS WEEK I WAS AT A MEETING THAT WE SPONSORED IN COLLABORATION WITH THE OFFICE OF RARE DISEASE RESEARCH AND DIFFUSE INTRINSIC GLIOMA, THE DEVASTATING CANCER WHERE WE HAVEN'T MADE PROGRESS. IN DECADES, A COUPLE OF YEARS AGO REMARKABLE DISCOVERY WAS MADE THAT THIS WAS A CANCER RELATED TO HISTONE GENE MUTATIONS AND THE FIRST CANCER RELATED TO HISTONE GENE MUTATIONS. SO ALL OF A SUDDEN YEARS OF RESEARCH ON CHROMATIN BIOLOGY AND HISTONE RESEARCH BECAME IMMEDIATELY RELEVANT TO THIS DISEASE SOME WHO NEVER HEARD DIPG RESEARCHERS EXAMPLE WHAT WE WERE DOING RESEARCH WE HAVE TO SUPPORT ABLE TO MAKE ADVANCES IN CHILDHOOD CANCERS IN THE FUTURE. I WILL FOLLOW THE QUESTIONS RAISED FOR US TO ADDRESS WHAT'S WORKING IN PRE-CLINICAL RESEARCH, PEDIATRIC PRE-CLINICAL TESTING PROGRAM, A RESEARCH CONTRACT SUPPORTED BY NCI, NATION WILD CHILDREN'S HOSPITAL IS THE PRINCIPLE INVESTIGATOR FOR THAT. EITHER (INAUDIBLE) WE HAVE BEEN TESTING WE COLLABORATED WITH MORE THAN 50 DIFFERENT PHARMACEUTICAL COMPANIES, WE HAVE EVALUATED MORE THAN 70 INVESTIGATIONAL AGENTS. LARGE MEASURE DIRECT ELECTRONICS PLANT PATIENT DERIVED XENOGRAPHS CAN BE USED TO PRIORITIZE AGENTS FOR EVALUATION. THERE'S OTHER -- SOME OF THE KEYS TO SUCCESS FOR THE PROGRAM, WE HAVE A MODEL NTA SO THEY CAN BE NEGOTIATED WITHIN ONE OR TWO MONTHS RATHER THAN A YEAR OR LONGER. THIS IS SOMETHING THE ADVOCACY COMMUNITY CAN HELP ENCOURAGE THROUGHOUT PRE-CLINICAL TESTING, ADOPTION OF MODEL NTAs THAT COULD BE ACCEPTABLE TO TECH TRANSFER OFFICES AND TO INDUSTRY. HAVING A CONSISTENT FUNDING SOURCE IS CRITICAL. AND BEING ABLE TO GO TO A COMPANY AND SAY IF YOU'LL PROVIDE WAS DRUG, WE CAN DO THIS BUT NOT ONLY AMOUNT OF TESTING TO INFORM HOW YOUR AGENT MAYBE RELEVANT TO CHILDHOOD CANCERS, THEN FINALLY WE HAVE A SYSTEMATIC CONSISTENT APPROACH TO TESTING, THIS IS IMPORTANT AND ENGENDERING CONFIDENCE IN PHARMACEUTICAL COLLABORATORS THAT WE HAVE A CONSISTENT WAY TOY APPROACH THE DRUGS, WE HAVE TO GIVE THEIR DRUG A FAIR RELIABLE TESTING APPROACH. A A NUMBER OF AGENTS THAT WE HAVE STUDIEDED TRANSITIONED FROM PRE-CLINICAL TESTING INTO THE CLINIC. WE HAVE -- SOME THAT ARE ALREADY IN THE CLINIC. SOME THAT ARE SURELY TO BE IN THE CLINIC. I'LL GIVE AN EXAMPLE OF ONE OF EACH. HEMATONIB IS AN AGENT WE LOOK AT AS A MEK INHIBITOR, ONE TARGETED AGENT THAT JOHN MENTIONED, THIS TARGETS THE MAP KINASE PATHWAY, WE HAVE STUDIED IT AGAINST 40 XENOGRAPHS CHILDHOOD CANCER XENOGRAPHS, IT HAD LITTLE OR NO ACTIVITY. FIRST IS LOW RATE ASTRO CYTOMA, IT HAS A BRAF MUTATION, WE SAW THESE NICE REGRESSIONS AT SEVERAL LEVELS, VERY HIGH ACTIVITY FOR THIS STUDY AGAINST THE LOW GRADE ASTRO CYTOMA XENOGRAPH. THIS TRANSITIONED TO THE CLINIC. THE PEDIATRIC BRAIN TUMOR CONSORTIUM HAS DONE A PHASE 1 TRIAL, IN THE PHASE 1 TRIAL THEY SAW SIMILAR RESULTS AS FOR PATIENTS WITH BRAF MUTATED LOW GRADE ASTRO CYTOMAS, NOW IN A PHASE TWO EXPANSION TO GET MORE EXPERIENCE, WITH THE AGENT IN LOW GRATE ASTRO CYTOMA PATIENTS WITH B RAF MUTATED TUMOR Z. THE SECOND EXAMPLE, THIS ONE THAT IS TRANSITIONING TO THE CLINIC. AND THIS IS AN EXAMPLE FROM A USING SARCOMA XENOGRAPH. THIS IS A PARP INHIBITOR, A DNA REPAIR INHIBITOR, BMN 673, FROM (INDISCERNIBLE) PHARMACEUTICALS. THE IDEA HERE WAS TO COMBINE SOMETHING THAT INHIBITS DNA REPAIR WITH SOMETHING THAT CAUSES DNA DAMAGE, THE FINDING WAS CONTROL ANIMALS THE TUMORS GROW AT QUICK RATE, EITHER SINGLE AGENT, THERE'S NO EFFECT BUT WHEN TWO AGENTS ARE PUT TOGETHER THE ANIMAL IS TREATED ONLY FIVE DAYS, THERE'S A REMARKABLE EFFECT WHERE EVEN AT 12 WEEKS WE'RE WAITING FOR THE TUMORS TO RECUR. THIS FINDING IS BEING TRANSLATED INTO THE CLINIC. AND WE WILL SHORTLY HAVE A PHASE 1 TRIAL. I THINK I'LL TRANSITION WITH THAT, WHAT IS WORKING IN CLINICAL RESEARCH. WE CAN DO PHASE 1 TRIALS QUICKLY, WE CAN GET THEM UP AND RUNNING WITH THE COG PHASE 1 CONSORTIUM WITH THE PEDIATRIC BRAIN TUMOR CONSORTIUM, WHEN THERE'S A COMMITMENT FROM THE COMPANY TO MOVE THE DRUG FORWARD. LIKE JOHN SAID RIGHT NOW THERE'S A PAUCITY OF PHASE 1 TRIALS. THIS IS ONE, THE (INAUDIBLE) COMPOUND WHERE THE COMPANY NOT ONLY WAS WILLING TO COLLABORATE TO DO THE PRE-CLINICAL TESTING BUT COLLABORATING DOING A PEDIATRIC PHASE 1 TRIAL TO THE PHASE 1 CONSORTIUM. THE DATA I SHOWED YOU GENERATED PROBABLY LESS THAN SIX MONTHS AGO. WITHIN LESS THAN A YEAR, WE'LL HAVE A PEDIATRIC PHASE 1 TRIAL THAT WILL BE SEEN IF WE CAN TRANSLATE THAT FINDING FROM PRE-CLINICAL AND INTO SETTINGS FOR USINGS SARCOMA OR OTHER CHILDHOOD SOLID TUMORS. WHAT ELSE IS WORKING? COG AND AND HIS COLLEAGUES, THERE'S EXCITING TRIALS THAT ARE ONGOING OR IN PLANNING STAGES NOW. JOHN MENTIONED THE PREZOTNIB FOR LYMPHOMA, (INDISCERNIBLE) IS ANOTHER AGENT. POST ARE -- WHEN THAT WAS KNOWN COG DEVELOPED A TRIAL WHERE COMBINING ONE OR THE OTHER OF THESE AGENTS WITH SYSTEMIC CHEMOTHERAPY, THAT'S EFFECTIVE AGAINST AANY PLASTIC LARGE CELL LYMPHOMA IN NEWLY DIAGNOSED PATIENTS SO THE DESIRED OUTCOME IS A HIGHLY EFFECTIVE REGIMEN TOLERATED. HEMATONIB IS IN PHASE 2 EXPANSION NOW. JOB TALKED ABOUT THE CD 19 DIRECTED THERAPYIES. SO WITH WE HAVE SOME TRIALS FOR SOME DISEASES THAT ARE PROMISING AND HIGH HOPES THAT THE RESULT OF THEM WILL BE POSITIVE. ANOTHER POINT IS CHILDHOOD CANCER MORTALITY IS DECLINING FROM 2002 TO 2010, THE RATE OF DECLINE 2.4% PER YEAR. AS A RESULT OF THE WORK OF THE CHILDREN'S ONCOLOGY GROUP AND OTHERS, INSTITUTIONS ALL OVER THE COUNTRY, PHYSICIANS, RESEARCHERS ALL OVER THE COUNTRY ENROLLING PATIENTS ON TRIALS, GETTING THE TRIALS GOING, WE SEE NEW TREATMENTS THAT ARE WORKING. THERE'S IS IT ENOUGH? ABSOLUTELY NOT. IS IT ACROSS ALL CANCERS? AGAIN, ABSOLUTELY NOT. WE HAVE THE REFRACTORY CANCERS WHERE THE DIPG HIGH GRADE GLIOMAS IN CHILDREN, METASTATIC SARCOMAS WHERE WE AREN'T SEEING THESE IMPROVEMENT IN MORTALITY SO THERE'S CHEERILY MUCH MORE WORK TO BE DONE. SO WHAT ARE THE CHALLENGES THEN, THOSE ARE SOME OF THE THINGS THAT ARE WORKING. WHAT ARE SOME OF THE CHALLENGES? IN PRE-CLINICAL RESEARCH ONE THING, THIS IS IN SOMEWHAT ON US TO ADDRESS, I THINK WE'RE INSUFFICIENTLY CLINICAL CRITERIA FOR CLAIMING ACTIVITY BASED ON PRE-CLINICAL TESTING. SO IN SOME WAYS IN THE (INAUDIBLE) SCHOOL OF DRUG DEVELOPMENT, ALL DRUGS ARE ABOVE AVERAGE, THEY'RE NOT ABOVE AVERAGE. WE SHOULD BE MORE READY TO SAY THIS ISN'T WORKING AS WELL AS WE WOULD HOPE. AND MOVE TO SOMETHING ELSE. I THINK YOU CAN HELP US APPLY PRESSURE TO DO THAT. A GOOD CANCER IS ONE THAT GOES AWAY, GOES AWAY COMPLETELY AND STAYS AWAY. GOOD DRUGS ARE THE ONES THAT MAKE THE CANCERS REGRESS, GO AWAY. I THINK WHICH NEED TO BE FOCUSING PRE-CLINICAL TESTING ON LOOKING FOR THOSE DRUGS THAT MAKE THE CANCER GO AWAY WHETHER IMMUNOTHERAPY, SMALL MOLECULE DRUGS, ANTI-P BODIES, WHATEVER IT IS. WE NEED TO AVOID GREAT INFLATION, HAVE HIGH CRITERIA FOR PRE-CLINICAL TESTING. THERE'S NOT ENOUGH FUNDING TO TO ALL THE TESTING WE COULD DO THAT BE CONTRIBUTORY. THERE ARE MORE MODELS THAT COULD BE STUDIED ORTHO TOPIC MODELS NOT WIDELY UTILIZED AS THEY COULD BE. WITH MORE FUNDING WE CAN DO MORE SYSTEMATIC TESTING THAT COULD CONTRIBUTE. WE LACK AGENTS THAT ADDRESS SPECIFIC GENOMIC LESIONS IN CHILDHOOD CANCERS. I'LL SAY MORE ABOUT THAT HERE. PHARMACEUTICAL COMPANIES ARE DEVELOPING DRUGS FOR THE TARGETS THAT ARE PRESENT IN ADULT CANCERS. WE HAVE GOT A NUMBER OF GENOMIC LESIONS THAT IN PRINCIPLE COULD BE TARGETED IN CHILDHOOD CANCER. EWS 51 FOR USINGS SARCOMA, FUSION PROTEIN FOR ALVEOLAR RHABDOMYOSARCOMA, THE K-23 M MUTATION THAT OKAY CAN CURS IN 80% OF DIPG, MORE THAN ONE ALTERATION FOR TUMORS MAKING AMPLIFICATION FOR NEUROBLASTOMA AND P WE NEED AGENTS TARGETING THESE SPECIFIC ALTERATIONS OR TARGETING THE SUSCEPTIBILITIES CREATED BY THESE ALTERATIONS. SO THERE'S A GREAT NEED, MAYBE IMMUNOTHERAPY AAS JOHN DESCRIBED WILL ADDRESS THIS. MAYBE SMALL MOLECULES WILL ADDRESS THIS BUT WE HAVE A PAUCITY OF APPROACHES ADDRESSING THESE SPECIFIC CHILDHOOD CANCER LESIONS. WE ALSO HAVE A CHALLENGE APPLYING TARGETED THERAPY THAT JOHN ALLUDED TO. AND JOHN MENTION AD PAUCITY OF MUTATIONS IN MANY CHILDHOOD CANCERS. MOST CHILDHOOD CANCERS LACK ACTIVATING MUTATIONS IN THE KINASES THAT ARE THE PRIMARY FOCUS OF ADULT TARGETED THERAPY DRUG DEVELOPMENT. WHEN WE LOOK AT THE CANCERS THAT KILL CHILDREN TODAY, THERE ARE EXAMPLES WHERE WE HAVE THE KINASE ALTERATIONS THAT ARE THERAPEUTIC TARGETS THAT GIVES REMARKABLE RESULTS, PH POSITIVE ALL, ANOTHER SUBSET OF ALL. LOW GRADE ASTRO CYTOMA THAT I MENTIONED IS A KINASE, A SUBSET OF NEUROBLASTOMA, NON-HODGE KIN LYMPHOMA BUT LARGE MEASURE, ALL THIS RESEARCH MAYBE NOT APPLICABLE IN A MAJOR WAY IN THE CHILDHOOD CANCER SETTING. ANOTHER CHALLENGE WE FACE, THIS BORDERS THE PRE-CLINICAL TO CLINICAL ARENA. HUNDREDS OF CHILDHOOD CANCERS HAVE BEEN SEQUENCED FROM PATIENTS AT DIAGNOSIS. ST. JUDE CHILDREN'S RESEARCH HOSPITAL WASU COLLABORATION, THE TARGET PROGRAM, A NUMBER OF OTHER PROGRAMS AROUND THE WORLD, WE HAVE GOT ENORMOUS AMOUNT OF GENOMIC INFORMATION ABOUT CHILDHOOD CANCERS AT DIAGNOSIS. THERE'S A MUCH SMALLER NUMBER SEQUENCED AT TIME OF TREATMENT FAILURE. THIS IS A REAL DEFICIT IN OUR UNDERSTANDING, WHAT ARE THE NO REGULAR CORRELATES OF TREATMENT FAILURE, HOW SIMILAR IS THE CANCER THAT RECURS TO THE ONE THAT WAS PRESENT AT DIAGNOSIS. ARE MULTIPLE FACTORS DIFFERENT OR JUST ONE OR TWO? MOST IMPORTANT ARE THERE RECURRING GENOMIC ALTERATIONS THAT CAN INFORM WHAT SHOULD WE -- THE THERAPEUTIC STRATEGIES THAT WE SHOULD BE PURSUINGING. SO THIS IS AN AREA, JOHN P HIT THE NAIL ON THE HEAD, A LOT OF ATTENTION NEEDS TO BE APPLIED IN THIS AREA. ANOTHER CHALLENGE IN CLINICAL RESEARCH, WE ARE INLEARNLY SMALL POPULATIONS, WE ADAPTED OVER THE YEARS WITH NATIONWIDE CLINICAL TRIALS TO ADDRESS THIS CHALLENGE. AS WE DEFINE PEDIATRIC CANCER, IT'S NOT JUST MED LOW BLASTOMA, AT LEAST FOR SUBSETS OF MEDULLAR BLASTOMA, NOT JUST ALL, IT'S MULTIPLE SUBSETS OF ALL TREATED DIFFERENTLY. EACH CANCER BEING SUBSETTED IN SMALL PATIENT POPULATIONS NEEDING TO BE STUDIED IN CLINICAL TRIALS, IS EXTRAORDINARILY CHALLENGING. BACK TO FUSION PROTEIN MAYBE IMPORTANT IN ARCLL BUT 1 OR 2%, IT'S EXTRAORDINARILY CHALLENGING TO IDENTIFY THOSE PATIENTS, IDENTIFY THE ONES WHO RELAPSED AND GET ENOUGH PATIENTS TREATED TO UNDERSTAND WHETHER FOR EXAMPLE, JACK 2 INHIBITOR MIGHT BE IMPORTANT. IT IS POINT WE NEED ACCRUAL BASE OF ONE OR TWO CONTINENTS TO CONDUCT CLINICAL TRIALS. IT'S VERY COMMON NOW TO HAVE COLLABORATIONS WITH NORTH AMERICA, WITH COG, AND MANY OTHER EUROPEAN COUNTRIES TO CONDUCT CLINICAL TRIALS. THAT'S A COMMON CIRCUMSTANCE NOW. ONE CONCERN, THIS IS OCCURS AT THE SAME TIME PHARMACEUTICAL COMPANIES, IN SOME CASES ACCOMPLISHING THEIR OWN PEDIATRIC CLINICAL TRIALS NETWORK. WE NEED TO BE VERY -- PERHAPS THIS IS AN AREA YOU CAN HELP IN, WE NEED TO MAINTAIN OUR ABILITY TO MOBILIZE A WHOLE COUNTRY OF PEDIATRIC PATIENTS SO WE CAN GET THE TRIALS IN A TIMELY MANNER AND NOT SPLIT OFF SO IN THE END P NOTHING GETS ACCOMPLISHED. IN TERMS OF WORKING WITH INDUSTRY, OUR PERSPECTIVE HOW WE CAN WORK WITH INDUSTRY AND PEDIATRIC RESEARCH IS BY SUPPORTING THE THE PRE-CLINICAL TESTING PROGRAM BY SUPPORTING THE PEDIATRIC BRAIN TUMOR CONSORTIUM, THE COG PHASE 1 CONSORTIUM, COG. THAT WE CAN LOWER THE ACTIVATION BARRIER FOR COMPANIES TO ENTER THE PEDIATRIC PRE-CLINICAL AND CLINICAL STATE. A COMPANY NEEDS TO BE FOCUSED ON WHAT'S MISSION CRITICAL FOR THE COMPANY. FIRST IN CLASS, GETTING TO THEIR AGENT APPROVED, ANY RESOURCES THEY WERE THEY HAVE TO DIVERT CAN BE DAMAGING TO THE COMPANY. BY COMPANIES ENTERING THE PEDIATRIC PRE-CLINICAL, CLINICAL ARENA, WITH A REDUCED RESOURCES ON THEIR PART, WE CAN MAKE IT EASIER FOR DRUGS TO ENTER PEDIATRIC TESTING DO IT FOR EXPERIENCED GROUPS OF INVESTIGATORS THAT CAN GET THE TRIALS DONE AS SAFELY AS THEY CAN BE AND EXPEDITIOUSLY. I MENTIONED WE HAVE MODEL NPAs, WE HAVE MODEL CRADA AGREEMENTS THAT DEVELOP IP ISSUES AND HELP EXPEDITE GETTING INTO THE CLINICAL -- INTO PRE-CLINICAL TESTING. SO THERE IS A QUESTION CURRENT PARADIGM WORKING THERE ARE A LOT OF PARADIGMS. HARD THE ADDRESS WHICH PARADIGM WE TALK ABOUT. THE ONE THING I WOULD DRAW YOUR ATTENTION TO IS PARADIGM THAT'S VERY -- THE EUROPEAN LEGISLATIVE INITIATIVE THAT PUT THIS AT THE FOREFRONT, THAT'S WHERE IT MOST ADVANCED. I CALL IT THE PHARMACEUTICAL REGULATORY PARADIGM. CHILDHOOD CANCER CLINICAL RESEARCH ON THE ADULT CANCER PRIORITIES OF PHARMACEUTICAL COMPANIES THROUGH CENTERS AND REGULATORY REQUIREMENTS. SO WITH THIS PROCESS AN AGENTS THAT GET PRIORITY, TYPICALLY WHICH ADULT INDICATIONS ARE SOUGHT WITH THE HIGHEST INCENTIVES FOR THE LARGEST ADULT CANCER MARKETS. SO WE HAVE PRIORITIZATION DECISIONS BEING MADE BY PHARMACEUTICAL COMPANIES, REGULATORY AGENCIES, WITH VARIABLE INPUT FROM THE PEDIATRIC CANCER COMMUNITY. AND I SAY THIS IS MOST ADVANCED BASED ON EUROPEAN LEGISLATION, TO ITS CREDIT FDA HAS REALLY TRIED TO GET INPUT FROM PEDIATRIC CANCER COMMUNITY AS ROBUST WAY AS POSSIBLE WITHIN THIS -- WITHIN THIS FRAMEWORK. WHAT THE ISSUE IS, I CAN SAY MORE ABOUT FAILURE BUT WE'RE LIMITED BY RESOURCES, YES, BUT THE NUMBERS OF PATIENTS LIMIT AS WELL THANKFULLY A SMALLER NUMBER BUT ONE TRIAL FOR ALVEOLAR MYOSARCOMA IN THE NEXT FIVE YEARS, WHAT THAT FOR NEW AGENT RATHER THAN WHAT'S THE BEST PEDIATRIC CLINICAL TRIAL FOR THIS SPECIFIC CHILDHOOD CANCER, WE MAKE MAY GET VERY DIFFERENT ANSWERS TO THE QUESTION. DISTINGUISHING ANY PEDIATRIC ONCOLOGISTS IN THIS ROOM, TAKE NEW CANCER DRUG, AND DEVELOP A MEDIA TRICK PROGRAM, THE BEST WAY TO DEVELOP THAT IN THE CHILDHOOD CANCER SETTING. BUT THAT'S A VERY DIFFERENT APPROACH OR VERY DIFFERENT QUESTION THAN SAYING WHAT IS THE BEST CLINICAL TRIAL THAT NEEDS TO BE DONE FOR HIGH RISK NEUROBLASTOMA, USINGS SARCOMA AND SO ON. I'M NOT A POLICY MAKER, DON'T KNOW HOW THINGS CAN BEST BE BE DONE. BUT WE NEED A SETTING WHICH THE PEDIATRIC RESEARCH COMMUNITY IS EMPOWERED TO MAKE PRIORITIZATION DECISIONS, AND THIS REQUIRES SECURE FUNDING FOR CLINICAL TRIALS THAT AREN'T DEPENDENT ON PHARMACEUTICAL COMPANY SUPPORT AS WELL AS UNHINDERED ACCESS TO AGENTS OF INTEREST. HOW WE GET TO THIS POINT AND MAINTAIN, I DON'T KNOW, BUT I THINK THIS APPROACH HAVING THE PEDIATRIC RESEARCH COMMUNITY PARADIGM MAKING REALLY LEADING THE PRIORITIZATION WITH CURE FUNDING ACCESS TO AGENTS HAS OUR BEST CHANCE OF PROGRESS OVER THE YEARS. SO THE FINAL THING I'LL END WITH IS A CHALLENGE IN CLINICAL RESEARCH. RESCUING ORPHAN DRUGS, THESE ARE OR ORPHAN DRUGS DEVELOPED FOR ADULT CANCER INDICATIONS BUT THEY FAIL IN THOSE ADULT CANCER INDICATIONS AND THOUGH THEY MAYBE OF INTEREST FOR ONE OR MORE CHILDHOOD CANCERS, WE DON'T HAVE THE CHANCE OF STUDYING THEM BECAUSE EAR NO LONGER IN DEVELOPMENT. I'LL SAY MORE ABOUT THE 14, 18 EXAMPLE. THE IDEA FOR OUR EXAMPLE, FIVE YEARS AGO THERE WERE PROBABLY TEN COMPANIES THAT HAD AGENTS IN DEVELOPMENT FOR MONOCLONAL ANTIBODIES AGAINST IGF INSULIN GROWTH FACTOR ONE RECEPTOR. AND THERE'S GREAT INTEREST IN USINGS SARCOMA, THIS WAS A CLASS OF AGENT THAT COULD BE POTENTIALLY IMPORTANT FOR USINGS SARCOMA. WE HAD ONE TRIAL WE WANTED TO DO WHERE WE COMBINED AN ANTIBODY WITH STANDARD CHEMOTHERAPY TO SEE IF THE ANTIBODY MADE THE CHEMOTHERAPY WORK BETTER AND IMPROVE OUTCOMES FOR USINGS SARCOMA. BEFORE WE GET THAT TRIAL OVER, ALL AGENTS DISAPPEARED. AND WE WERE LEFT NEVER ABLE TO TEST THAT PARADIGM. IT IT MIGHT NOT HAVE WORKED BUT AT LEAST A CHANCE TO TEST IT. WE WERE ABLE NCI WAS ABLE TO ESTABLISH A COLLABORATION WITH AMGEN, WHEREBY THEY PROVIDE US WITH RAW MATERIAL, WITH THE BULK ANTIBODY, WE WILL VILE IT AND COG WILL CONDUCT ONE CLINICAL TRIAL, PROOF OF PRINCIPLE CLINICAL TRIAL TO SEE IF IN FACT THIS CLASS OF AGENTS IS IMPORTANT FOR USINGS SARCOMA. I KNOW THERE ARE OTHER AGENTS THAT WILL NEED RESCUING IN THE FUTURE. I'LL 1418 MODEL AS AGENTS THAT CAN BE RESCUE AND HOW PEDIATRIC SPECIFIC DRUGS CAN BE DEVELOPED. SO CHIMERIC 1418 IS A MONOCLONAL ANTIBODY, IT TARGETS GD-2, GD-2 IS SOMETHING ON THE SURFACE OF ALMOST ALL NEUROBLASTOMA CELLS, GD-2 EXPRESSION OF NORMAL TISSUES, FROM SCANNING NERVE CELLS, 1418 CAN KILL CANCER CELLS THE WAY ANTIBODIES WERE ABLE TO KILL CANCER CELLS BUT IT WAS UNSUCCESSFUL IN ADULT CANCER INDICATIONS. IN THE LATE 1990s A GROUP OF PEDIATRIC ONCOLOGISTS WHO HAVE BEEN STUDYING CHIMERIC 1418 FOR NEUROBLASTOMA CAME TO NCI AND ASKED NCI TO MAKE CHIMERIC 1418 SO A CLINICAL TRIAL CAN BE CONDUCTED. NCI AGREED TO MANUFACTURE THE CHIMERIC 1418. THIS STUDY WAS OPENED IN 2001. THE STUDY HALF THE CHILDREN GOT THE ANTIBODY, HALF GOT STANDARD THERAPY WITHOUT THE ANTIBODY AND IMMUNOTHERAPY APPROACH. POSITIVE RESULTS WERE ANNOUNCED IN 2009. THIS IS FROM THE PUBLICATION A YEAR LATER IN THE NEW ENGLAND JOURNAL OF MEDICINE. IN BOTH INCREASE SURVIVAL, OVERALL SURVIVAL IMPROVED BY THE CHIMERIC 1418 ANTIBODY. AGAIN, SOMETHING THAT DO NOT HAVE ADULT TUMOR FOR WHICH IT WAS BEING DEVELOPED. WE GOT THESE RESULTS, WE FED ABOUT A PROCESS OF COMPETING FOR PHARMACEUTICAL COLLABORATORS. WE CAN'T COMMERCIALIZE, DEVELOP AGENTS COMMERCIALLY AT NCI. WE HAVE THIS COMPETITION, THOUGH WE HAVE POSITIVE PHASE 3 TRIAL THERE'S STILL A LOT OF WORK THAT HAD TO BE DONE BEFORE THE AGENT CAN BE COMMERCIALLY APPROVED, BY FDA. AS A RESULT OF COMPETITION, WE SELECTED UNITED THERAPEUTIC AS OUR PHARMACEUTICAL COLLABORATOR. THEY HAD MONOCLONAL ANTIBODY PRODUCTION FACILITY. IN THE TIME SINCE THEY HAVE BEEN SELECTED THEY HAVE DONE A FANTASTIC JOB IN DOING THE THINGS ALL THE STEPS NECESSARY TO MOVE TOWARDS FILING VOAs SO IT CAN CAN BE COMMERCIALLY APPROVED. AS OF TODAY CHILDREN WITH NEUROBLASTOMA NO LONGER RECEIVE THE NCI MANUFACTURED PRODUCT. THEY'RE NOW RECEIVING THROUGH CLINICAL TRIAL UNITED THERAPEUTICS MANUFACTURED PRODUCT, AND HOPEFULLY WILL BE SUBMITTED WITHIN THE NEXT COUPLE OF MONTHS. SO THIS PROVIDES POTENTIAL MODEL FOR HOW PEDIATRIC SPECIFIC AGENTS COULD BE DEVELOPED. IT WOULDN'T HAVE BEEN DEVELOPED WITHOUT PUBLIC FUNDING, AT MULTIPLE STEPS IN THE DRUG DEVELOPMENT CYCLE. IT TOOK THE ACADEMIC VISITORS AND FOLKS LIKE LSU AND -- DOING THE PRE-CLINICAL WORK WITH NCI SUPPORT CHILDREN'S ONCOLOGY GROUP BLASTOMA COMMITTEE JOHN AND SUE COHEN AND ALL THE OTHERS IN THE NEUROBLASTOMA COMMITTEE AND MANY INSTITUTIONS, AND AT THE END TOOK THE PHARMACEUTICAL SECTOR ABLE TO STEP IN ONCE THE PROJECT HAD BEEN SUFFICIENTLY DERISKED AND GO FINAL STEPS WHICH IS SUBSTANTIAL BUT NONETHELESS GO TO FINAL STEPS TO MAKE A COMMERCIAL PRODUCT. SO AGAIN, I THINK THIS PROVIDES AN EXAMPLE HOW IN THE FUTURE WE MIGHT BE AUTOMOBILE TO REPLICATE THIS FOUR NOVEL AGENTS FOR UNCOMMON LIFE THREATENING DISEASES USING THESE MULTIPLE SUPPORTS. SO IN CONCLUSION FUTURE OF PROGRESS REQUIRES PEDIATRIC FOCUSED DRUG DEVELOPMENT EFFORT FROM PRE-CLINICAL TO CLINICAL IDENTIFYING PATHWAYS TO CURE FOR ALL CHILDREN WITH CANCER. WE SUPPORT PRE-CLINICAL DISCOVERY ALL THE WAY THROUGH TO DEFINITIVE TESTING BUT IT TAKES THE SUPPORT FROM ADVOCACY COMMUNITY, ALL THE GRANTEES THAT NCI SUPPORTS IN THE PHARMACEUTICAL COLLABORATIONS THAT ARE CRITICAL FOR BRINGING EFFECTIVE NEW TREATMENTS TO CHILDREN. THANK YOU. [APPLAUSE] >> DR. SMITH, THANK YOU, VERY MUCH. WE'RE RUNNING A TAD LATE BUT THE SMART PEOPLE IN THE NCI OFFICE WHEN THEY PRINTED THE AGENDA BOOKED IN A LONG BREAK, A HALF HOUR BREAK, AND I'M WILLING TO CANNIBALIZE THE BREAK A BIT SO WE CAN GET GOOD QUESTIONS GOING. IF THERE ARE QUESTIONS SPECIFIC TO DR. SMITH, THAT WOULD BE GREAT, THEN WE'LL HAVE TIME TO ADDRESS THE THREE PRESENTERS AT THE END. SO QUESTIONS. >> DR. SMITH IN ONE OF YOUR SLIDES YOU INDICATED >> PEDIATRIC RESEARCH COMMUNITY, LARGE ACADEMIC RESEARCH COMMUNITY AND OTHER GROUPS LIKE THAT. THERE'S DISTINCTION BETWEEN ACADEMIC INVESTIGATORS FOCUSEDDED ON SPECIFIC DISEASES A NUMBER HAS PEDIATRIC ONCOLOGISTS AND TALENTED PEDIATRIC ONCOLOGISTS ARE MAKING IMPORTANT CONTRIBUTIONS FOCUS MORE ON THE DISEASE ITSELF. >> SUSAN, YOU HAVE A QUESTION? >> MAYBE DR. HELMAN WILL COVER THIS IN HIS COMMENT. KEEPING THE EYE ON THERAPIES AND DRUG DEVELOPMENT DO YOU HAVE DRUGGABLE TARGETS THAT ARE DRUGGABLE TARGETS? WHERE THERE IS ANY SORT OF VIRAL COME POINT TO PEDIATRIC CANCERS THAT MIGHT ALREADY HAVE OR COULD HAVE >> IT'S A GREAT QUESTION. WITH CHILDHOOD CANCER AS OPPOSED TO I ADULT CANCER THAT GO THROUGH STAGES OF DEVELOPMENT WHERE THE POTENTIAL STEPS OF INTERVENTIONAL ALONG THE WAY, TO THIS POINT WE DON'T HAVE THE PRE-CURSOR LESION THAT WE CAN POINT TO, IT MAYBE INHERENT DIFFERENCE BETWEEN KARENS OF ADULTS APPROXIMATE CANCERS OF CHILDREN, RAN DIED RABDOID TUMOR THERE'S ONE MUTATION. YOU DON'T NEED OPPOSED TO CASH FLOW RECTAL CANCER WHERE THE MOIETY STEP CARCINOGENESIS MODEL WITH MANY OF OUR CHILDHOOD CANCERS, IT'S PROBABLY ONE OR TWO MUTATIONS, THAT'S RELATED TO A CELL OF ORIGIN UNIQUELY SUSCEPTIBLE TO TRANSFORMATION, THEY'RE PROBABLY DEVELOPMENTAL FACTORS THAT RELATE TO WHY ONE OR TWO MUTATIONS TRANSFORM A CELL INTO CANCEROUS LESION IN A CHILD. >> I WOULD ANSWER THAT SLIGHTLY DIFFERENTLY BECAUSE THERE IS A PERFECT EXAMPLE. ONE THEY'RE RARE, NOT DISAGREEING IN GENERAL THERE IS NOT ABILITY TO STUDY IN COLON CANCER OR POLYP. HOWEVER, IN THE INTRAMURAL PROGRAM, UNDER THE LEADERSHIP OF (INDISCERNIBLE) STUDYING NEUROFIBROMATOSIS. WHAT WE KNOW, IS PLEXI FORM NEUROFIBROMAS, A BENIGN LESION, 10 TO 12% OF PATIENTS DEVELOP A MA ANYTHING FANTASTIC TUMOR CALLED PERIPHERAL MALIGNANT NERVE SHEATHE TUMOR. WE HAVE BEEN WORKING THE 5 TO 10 YEARS TO TRY TO UNDERSTAND HOW WE MIGHT -- AND WE KNOW IN FACT THESE PLEXI FORM, ABOUT 50% PATIENTS WITH MPNST HAVE NF-1 AS PRECURSOR LESION. THEY ALL HAVE PLEXI FORM NEUROFIBROMAS AS PRECURSOR LESION. THESE LESIONS GROW VERY QUICKLY, MUCH MORE QUICKLY MANY EARLY CHILDHOOD. THAN THEY DO LATER. YOU CAN SEE THESE BEAUTIFUL INFANTS AND WITHIN THREE YEARS THEY HAVE A PLEXI FORM AND WITHIN TEN YEARS THEY'RE DEFORMED. BUT ONLY 10% OF THOSE WILL GO ON TO DEVELOP A MALIGNANT LESION. WE NOW HAVE A DRUG THAT INTERESTINGLY SEEMS TO BE VERY EFFECTIVE IN TARGETING THE PRE-HAOMA LEG THAN HE'S. THE SAME MEMBER INHIBITOR THAT JOHN MENTIONED. HERE THE PROBLEM WILL BE HOW DO WE DEVELOP CLINICAL TRIAL DESIGN THAT CAN LET US FIGURE OUT IS IT WORTH EXPOSING PATIENTS. SO THERE ARE A LOT OF ISSUES BUT THERE'S RARE PRE-CLINICAL OR RARE PRE-DISPOSITION LESIONS IN CHILDREN THAT WILL MAKE -- FORCE US TO DO DIFFERENT TRIAL DESIGNS TO TRY TO UNDERSTAND HOW TO STUDY THEM. BUT THEY ARE RARE. >> LET ME JUMP IN ON THAT ONE. IT MAY NOT BE WHAT YOU'RE AFTER. THIS IS AN EXAMPLE FROM PEDIATRICS, NOT PEDIATRIC ONCOLOGY BUT HPV VACCINE, IT IS ABSOLUTELY A PEDIATRIC FOCUSED AND HAS ENORMOUS IMPACT. SO YES, THEY ARE CANCERS THAT OCCUR DURING ADULT HOOD BUT THE INTERVENTION IS PEDIATRIC INTERVENTION. SO THAT'S THE BEST EXAMPLE OF AN INTERVENTION WITH A VIRUS AND PREVENTION STRATEGY THAT THERE'S MOUNTING DATA AS FAR AS TRANSFORMING THE DISEASE CERVICAL CANCER BY INTERVENING DURING PEDIATRICS. >> HEPATITIS VIRUS PROBABLY AS WELL. >> IN CERTAIN POPULATIONS. CHILDHOOD IMMUNIZATIONS WILL HAVE IMPACT BUT THAT MAY NOT BE REALIZED UNTIL ADULTHOOD. >> I WANT TO ADD A PICK, MAY NOT BE WHAT YOU'RE GETTING AT BUT THE NCI INVESTED HEAVILY IN A FEW DIFFERENT DISEASES AND GENOME WIDE ASSOCIATION STUDIES TO UNDERSTAND WHY CERTAIN CHILDREN DEVELOP NEUROBLASTOMA OR USINGS SARCOMA AND NOT OTHERS. -- USING EWING SARCOMA. THIS WILL RESULT IN PREVENTION STRATEGY, THE UNDERSTANDING OF WHY CERTAIN KIDS DEVELOP THE DISEASE DOES HAVE THERAPEUTIC POTENTIAL AT LEAST IN IDENTIFYING THE KEY GENETIC FACTORS THAT ARE TAKEN ADVANTAGE OF AS THE TUMOR ARISES. I THINK IT SPEAKS TO YOUR QUESTION A LITTLE BIT. >> THANK YOU. LET'S TAKE ONE MORE. THEN WE'LL MOVE TO DR. HELMAN, DAVID ARONS. >> THANK YOU FOR YOUR PRESENTATION AN HELPING US UNDERSTAND THE LANDSCAPE AND THE IMPORTANCE OF THE PRE-CLINICAL TESTING PROGRAM. YOU MENTIONED FUNDING FOR THAT PROGRAM EARLY IN YOUR PRESENTATION. CAN YOU HELP AS ADVOCATES UNDERSTAND FUNDING FOR THAT PROGRAM IN GENERALITY, IS IT ON SOLID GROUND, WHAT DO WE KNOW GIVEN CRITICALITY IN THIS PRONECESSARY >> I THINK IT WAS APPROVED FOR RECOMPETITION, LIKE ALL NIH PROGRAMS THEY'RE TERM LIMITED AND P HAVE TO BE APPROVED AGAIN SO IT WILL BE RECOMPETED THIS YEAR. AND SO I THINK WE HOPE THEY'LL BE FUNDS TO -- SOME FUNDS ARE ALLOCATED FOR THE RECOMPETITION. >> THANK YOU VERY MUCH. LEE, WOULD YOU LIKE TO -- >> I DECIDED TO DOING SOMETHING DIFFERENT TODAY. I DECIDED SINCE I WAS TALKING TO A DIVERSE AUDIENCE RATHER THAN A USUAL SCIENCE TALK WITH THE SLIDES, AND I KNEW MALCOLM AND JOHN WERE GOING TO DO THAT BECAUSE WE DISCUSSED DOING IT, I DECIDED I WAS JUST GOING TO DO A TALK. AND I THINK FOR SAVING SOME TIME, I'M GOING TO TURN MY TALK A LITTLE UPSIDE DOWN AND START WITH WHAT IS NECESSARY AND TRY TO POSE CHALLENGES AN QUESTIONS TO THE ADVOCACY COMMUNITY. I THINK WHAT I THINK IS NEEDED IN MANY WAYS REITERATES WHAT YOU HAVE HEARD FROM THE PREVIOUS TWO SPEAKERS. SO I WOULD SAY ONE OF THE CRITICAL NEEDS WE HAVE, MANY EXAMPLES, THE IGF-1 RECEPTOR SAN EXAMPLE, I THINK WITH THE PARP INHIBITOR,AS A IMMUNITY WE NEED TO UNDERSTAND WHEN WE SEE RESPONSES IN A RARE TUMOR, OF TEN OR 15 PERCENT AND THOSE PATIENTS DO EXTRAORDINARILY WELL, WE NEED TO SET UP FRONT WAYS THAT MAKES THOSE PATIENTS EXTRAORDINARY RESPONDERS. RIGHT NOW THE PEDIATRIC COMMUNITY HAS NO WAY OF DOING THAT. AND WE ARE LAGGING BEHIND. IT HURT MESS BECAUSE THE PEDIATRIC CANCER COMMUNITY WAS ALWAYS AT THE FOREFRONT. WE SET THE WORLD HOW YOU DO ALL, HOW YOU COMBINE THERAPIES. WE ARE NOT GENERATING THAT INFORMATION. SO WHY AREN'T WE GENERATING THAT INFORMATION? IT STEMS TO THE NEXT ISSUE THAT JOHN BROUGHT UP I'M GOING TO PUSH AND LOBBY HARD FOR THIS BECAUSE WE DOPE GET BIOPSIES. AND P THERE ARE ISSUE REGARDING BIOPSIES IN PEDIATRIC CANCER PATIENTS. WHAT WE KNOW, IF WE RELY ON A DIAGNOSTIC IN BIOPSY IN A PATIENT DONE THREE YEARS AGO WHEN THEY WERE DIAGNOSED AND THEY COME ON WITH EXPERIMENTAL STUDY THREE YEARS LATER WHAT WE KNOW FOR SURE IS THE TUMOR LOOKS MUCH DIFFERENT THAN WHAT WE CAN LOOK AT FROM A BIOPSY DONE THREE YEARS EARLY EARLIER. SO I -- WE'RE ACTUALLY DEVELOPING AN INTERNATIONAL STUDY, A SLIGHTLY DIFFERENT BUT SIMILAR TO THE PARP INHIBITION INHIBITOR STUDY MALCOLM DESCRIBED. AND WE DECIDED TO ABSOLUTELY REQUIRE ON STUDY BIOPSY. I CAN'T TELL YOU DISCUSSION, ARGUMENT, AND I JUST SAID LOOK, I THINK IT'S MORE UNETHICAL TO DO A STUDY WHERE YOU KNOW SOME PATIENTS RESPOND BUT NOT ALL AND IN THE END NOT KNOW WHY THOSE PATIENTS RESPOND. SO I THINK YOU CAN MAKE THE ARGUMENT IT'S UNETHICAL NOT TO DO A BIOPSY. AS JOHN SAID IN THE YEAR 2014, WE ARE ABSOLUTELY GOOD AT DOING BIOPSIES WITH INTERVENTIONAL RADIOLOGISTS WHERE THE COMPLICATION RATE IS NOT MUCH MORE THAN A VENAL PUNCTURE. OF COURSE IF WE THINK IT'S GOING TO BE -- WE'RE DOCTORS FIRST, IF WE THINK IT IS RISK TO TO THE PARK WE WOULDN'T DO IT. WHAT I HAVE LEARNED IN 20, 25 YEARS OF DOING CLINICAL STUDIES IS IF YOU DON'T MANDATE A BIOPSY, AND MAKE AN ELECTIVE YOU GIVE 20, 25% OF THOSE PATIENTS. AND THINK ABOUT A RARE DISEASE WHERE ONLY 25% GET BIOPSY WE NEVER HAVE THE NUMBERS TO KNOW ANYTHING. SO I THINK DOING STUDIES WHERE WE LEARN WHY SOME PATIENTS RESPOND AND SOME DON'T, REQUIRES BY NECESSITY INSISTING WE GET MATERIAL PRIOR TO STUDYING ON STUDY, WE NEED OUR ADVOCATES TO HELP US WITH THAT. WE GET PUSH BACK CONSTANTLY FROM OUR IRBs, FROM REGULATORY AGENCIES. WE CAN DO IT SAFELY, I WOULD ARGUE IT'S A REAL PROBLEM AND IT'S HOLDING THE FIELD BACK. THE OTHER AREA I WOULD SAY REALLY REQUIRES SOME THOUGHT. AGAIN, I THINK BOTH -- CERTAINLY JOHN MENTIONED, I THINK MALCOLM MENTIONED IT, IT IS TAKING US WAY TOO LONG TO GET FROM A NEW TARGETED AGENT TO DOING COMBINATION THERAPY. IT TOOK THE ADULT FIELD TOO LONG BUT THERE ARE NO EXAMPLES YET OF TWO TARGETED AGENTS IN PEDIATRIC CANCER BECAUSE WE SPEND YEARS DEFINING, IT JUST TAKES US TOO LONG. PEDIATRIC CANCER WAS THE FORWARD IN THE 1960s THAT QUICKLY IDENTIFY THAT YOU CAN'T CURE PATIENTS WITH SINGLE AGENT THERAPY. ALL WAS THE PERFECT EXAMPLE OF THAT, THEY FOUND AN EFFECTIVE DRUG. PROLONGED LIFE BY 6, 8 WEEKS, NOW WE'RE USING FOUR, SIX DRUG COMBINATIONS. SO WE HAVE TO FIGURE OUT WAY AS COMMUNITY TO GET SIGNAL THAT THIS DRUG HAS ACTIVITY AND P COMBINE IT RATIONALLY AS QUICKLY AS POSSIBLE. I THINK AGAIN, THE ADVOCACY COMMUNITY CAN HOLD OUR FEET TO THE FIRE, AND HELP FIGURE OUT HOW TO DO THAT IN A MUCH MORE EFFICIENT WAY. LASTLY, LET ME MOVE BACK TO THE PREVIOUS THING. YOU SAW THIS VERY EXCITING DATA THAT MALCOLM SMITH SHOW WITH THE THE PARP INHIBITOR. THAT'S (INDISCERNIBLE) WHERE THEY SAW FANTASTIC RESPONSES IN MICE. SO WE HAVE DONE A SIMILAR STUDY, WE SEE EXACTLY THE SAME THING IN THE CELL LINE HE SHOWED YOU TC- 71. BUT I HAVE ANOTHER MODEL OF EWING'S SARCOMA THAT DOESN'T RESPOND AT ALL TO THE SAME COMBINATION. SO WE ALREADY KNOW PATIENTS THAT DO NOT RESPOND. SO WE'RE TRYING TO MODEL WHAT THE DIFFERENCES ARE IN OUR MOUSE MODEL BUT WE NEED TO GET THAT INFORMATION IN THE PEDIATRIC STUDIES THAT STUDY THAT COMBINATION AND THE WAY WE GET THAT INFORMATION IS BY OBTAINING SAMPLES OF THE TUMOR. OTHERWISE WE'RE GOING TO BE THROWING UP OUR HANDS. JUST ANOTHER EXAMPLE I DID NOT WANT TO MENTION. I THINK WE ALSO NEED, WE NEED TO RETHINK AND COME UP WITH NEW STRATEGIES FOR HOW WE DO CLINICAL TRIALS. AND AGAIN I THINK THERE ARE SEVERAL ISSUES THAT WE'RE LAGGING BEHIND, I THINK ADVOCATES CAN PUSH US A LITTLE BIT HERE. SO ONE IS THE CONCEPT OF FOR LACK OF BETTER TERM, BECOMING USED IN THE ADULT MEDICAL ONCOLOGY COMMUNITY, BASKET STUDY. SO WE HAVE TARGETD AGENTS, MEC INHIBITOR, BRAF INHIBITOR, ALK INHIBITOR. AND MEDICAL ONCOLOGY COMMUNITY THEY'RE SETTING UP STUDIES WHERE IF YOU HAVE A TUMOR WITH A MEK IT CAN GO WHETHER DOESN'T MATTER COLON CANCER MELANOMA OR BREAST CANCER. WE DON'T HAVE THOSE STUDIES YET IN PEDIATRIC CANCER AND WE NEED THEM. WE DO KNOW IN FACT THERE ARE REASONS THAT EVERY PATIENT WITH BRAF MUTATION, WE KNOW FOR EXAMPLE MELANOMA PATIENTS RESPOND TO BRAF MUTATION, INHIBITORS IF THEY HAVE A BRAF MUTATION. COLON CANCER PATIENTS DON'T. BUT THEY GOT THE DRUG AND WE FIGURED OUT WHY THEY DON'T. THE REASON THEY DON'T IS COMPLICATED, I DON'T WANT TO GET INTO SCIENCE BEHIND IT. BUT I WOULD BE WILLING TO BET BECAUSE PEDIATRIC CANCERS ARE MORE LIKE OR ALMOST ALLOMYCES CHEMOAL TUMOR, WE'LL HAVE A -- ALMOST ALL MESENCHYMAL TUMOR, WHETHER IT HAPPENS IN A RAD DOE MYOSARCOMA OR EWING'S CAR SARCOMA OR GLIAL BLASTOMA WILL RESPOND TO THAT SAME INHIBITOR SO MAYBE WE SHOULDN'T TREAT PATIENTS IN PHASE 2 STUDIES, BY HISTOLOGY BUT TREATING BY GENETIC. THAT'S CALLED A BASKET STUDY, WE HAVEN'T DONE THAT YET IN PEDIATRICS AND I THINK ADVOCATES COULD HELP US. SO THAT'S ONE CLINICAL TRIAL DESIGN, WE HAVEN'T TAKEN ADVANTAGE OF AND WE NEED TO DO IT. THE SECOND ONE, THIS HELPS ME DRIVE HOME THE POINT OF ONE OF JOHN'S FIRST SLIDES, THE PRICE OUR PATIENTS ARE PAYING NOW, FOR WORKING THERAPIES 15, 20 YEARS AGO, WE'RE JUST LEARNING THE PRICE THEY PAY, PATIENTS WITH AOL WE CURED EARLY IN OUR CAREERS, WHEN WE SEE AGE 35, 45, THEY'RE A PAIR. THEY HAVE PAID A SIGNIFICANT PRICE. NONETHELESS WE'RE CURING 85% OF PATIENTS WITH ALL. SO HOW DO WE TEST THERAPIES THAT MAY DECREASE TOXICITIES 20 YEARS HENCE? IN A SETTING WHERE WE HAVE 85% CURE RATE. THAT'S A CHALLENGE. I'M NOT SURE HOW TO DO IT FRANKLY BUT IT'S A REAL CHALLENGE. WE KNOW IF WE CONTINUE USING THE SAME THERAPIES THAT WE HAVE THAT PATIENTS ARE -- HAVE ISSUES 20 YEARS LATER. I THINK WE MADE PROGRESS BY INTENSIFYING THERAPY AND P ONLY THOSE PATIENTS THAT SEEM TO NEED IT AND BACKING OFF LATE. BUT THOSE ARE REALLY -- THOSE ARE TOUGH QUESTIONS FOR THE FIELD. I THINK IT'S AN OPPORTUNITY FOR THE PEDIATRIC COMMUNITY TO TEACH THE ADULT COMMUNITY BECAUSE WE HAVE MORE SURVIVORS SO WE HAVE A COHORT OF SURVIVORS, WE NEED TO LEARN HOW TO DO STUDIES WE CAN ASK QUESTIONS SAFELY ABOUT HOW TO MINIMIZE TOXICITY IN PATIENTS THAT HAVE 85, 90% CURE RATE. THOSE REALLY HARD. THAT WOULD BE AN INTERESTING DISCUSSION WITH OUR CONSUMERS. I FIND THOSE DISCUSSIONS IN OUR PATIENTS VERY DIFFICULT TO HAVE BECAUSE OF COURSE WHEN YOU WORRY ABOUT MORTALITY OF YOUR CHILD, YOU SAY I'LL DO ANYTHING. 25 YEARS LATER YOU DON'T ALWAYS FEEL THAT WAY. THAT'S ANOTHER CHALLENGE. SO MAYBE IN THE LAST MINUTE I'LL JUST GIVE YOU A BROAD OVERVIEW WHICH IS WHAT I WAS GOING TO START WITH ABOUT THE INTRAMURAL PROGRAM BECAUSE IT IS UNIQUE. I THINK ANOTHER THING TO DO BETTER IS MAKE INTRAMURAL PEDIATRIC CANCER PROGRAM BE MORE COMPLIMENTARY TO THE NATIONAL PROGRAM AS DPEMLY FEWED BY COOPERATIVE GROUP. I THINK THE INTRAMURAL PROGRAM HAS THE ABILITY TO DO MUCH MORE INTENSIVE STUDIES WHERE WE CAN GET IMAGING, WE CAN DO PHARMACODYNAMICS, WE CAN DO THESE BIOPSIES, WE CAN DO THE SEQUENCING. WE NEED TO THINK HOW TO USE THE INTRAMURAL PROGRAM TO BETTER INFORM BIGGER STUDIES AND ARE COMPLIMENTING WHAT'S ALREADY GOING ON THROUGH CHILDREN'S ONCOLOGY GROUP. ONE AREA WE HAVE PUT PARTICULAR EMPHASIS ON IN THE INTRAMURAL PEDIATRIC ONCOLOGY PROGRAM RIGHT NOW IS IN DEVELOPING IMMUNOTHERAPEUTIC MORTALITIES BECAUSE -- MODALITIES BECAUSE IT IS, THE PHARMACEUTICAL INDUSTRY HASN'T ENGAGED MUCH UNTIL CHECK POINT INHIBITORS BECAME AVAILABLE, NOW SUDDENLY NOVARTIS AND P BRISTOL MYERS SCWIBB ARE INTERESTED BUT IT'S A TOUGH AREA TO GET SUPPORT TO DO BIG STUDIES SO THAT'S AN AREA THE INTRAMURAL PROGRAM FOCUSED ATTENTION TO PUSH THE FIELD FORWARD BUT THERE ARE OTHER OPPORTUNITIES IN IMAGING WHERE WE MIGHT GET BETTER EARLIER SIGNALS AND IN DOING THE STUDIES THAT HELP US TURN A DRUG THAT MAY WORK IN 30% OF PATIENTS. AND BE ABLE TO IDENTIFY THEM UP FRONT SO THAT NOW THE NEXT STUDY THAT GETS DONE WE TREAT MUCH LESS PATIENTS BUT WE GO FROM A 30% RESPONSE RATE TO A AN 85, 90% THAT'S THE HOLY GRAIL BUT PIT'S HAPPENING NOW. HAPPENING IN THE MEDICAL ONCOLOGY COMMUNITY AND WE NEED TO MAKE SURE WE PUSH TO MAKE IT HAPPEN IN THE PEDIATRIC ONCOLOGY. SO I THINK I'LL STOP THERE, AT LEAST THERE'S A FEW MINUTES FOR OPEN DISCUSSION, MAYBE WE CAN TAKE A LITTLE TIME. >> SO NOW I WOULD PUT LESS RESTRICTION ON THE QUESTIONS. AND SAY THAT NOT ONLY SHOULD WE TAKE QUESTIONS FROM DR. HELMAN'S PRESENTATION BUT YOU HAVE HEARD ALL THREE BASIC BRIEFINGS IN A SENSE. LET'S OPEN THE FLOOR TO QUESTIONS AND GO TO GENERAL TOPICS WE CONSIDER. >> WHAT ARE ETHICAL CONSIDERATIONS AND REASONS WHY WE'RE NOT GETTING BIOPSY UPON RECURRENCE? >> I'M HAPPY TO TAKE THE FIRST CRACK AT THAT. I THOUGHT A LOT ABOUT THIS, I MEAN CLEARLY, THE BASIC PRINCIPLES PROSPECT FOR BENEFIT HAS TO BE THERE. WE HAVE THE INFORMATION TO DESIGN A CLINICAL TRIAL WHERE THAT BIOPSY WILL BE USED TO ASSIGN A TRIAL TO THE TREATMENT WHERE THE CHILD HAS PROSPECT FOR BENEFIT. SO THERE'S TWO STAGINGS, BIOPSY, IS THERE ANY INFORMATION THAT CAN BE USED. IF SO, ACTIONING THAT RESULT. THAT'S VERY DIFFERENT A CLINICAL TRIAL OF AN AGENT WHERE WE WOULD LOVE THE BIOPSIES FOR RESEARCH BUT IT'S DRUG X AND SECONDARY OR TERTIARY AIM OF THE STUDY, WE WANT TO GET TISSUESES TO THE LAB, THERE I DON'T THINK WE CAN MANDATE. I WOULDN'T. SO IT REALLY COMES DOWN TO THE DESIGN OF CLINICAL RESEARCH STUDY AND HOW WE'RE GOING TO OPERATIONALLIZE IT. >> LET ME DRILL DOWN MORE. THERE ARE FEDERAL REGULATIONS FOR SPECIAL PROTECTIONS FOR CHILDREN. YOU PROBABLY ARE FAMILIAR WITH IT BUT ONE IS THE ONE JOHN ALLUDED TO. THERE HAS TO BE PROSPECT FOR DIRECT BENEFIT MEANING IF YOU DO A PROCEDURE GREATER THAN MINIMAL RISK, IN SOME WAY THAT HAS TO HAVE THE POTENTIAL TO DIRECTLY BENEFIT THAT TRIAL, THAT'S WHERE JOHN DRAWS THE DISTINCTION, WE LOVE MATERIAL FROM EVERY RELAPSE CHILD BUT IF THERE'S NO BENEFIT TO THAT CHILD, PUTTING THAT CHILD THROUGH A PROCEDURE IS NOT GENERALLY WOULD NOT BE ALLOWED UNDER CURRENT FEDERAL REGULATIONS. WE DO HAVE TO HAVE BECOME BETTER DESIGNING TRIALS THAT OFFER THAT PROSPECT. AND WHERE I WOULD CAUTION ALL OF US IS FOR SOME DISEASES WE CAN CLEARLY MAKE THAT STATEMENT. WE HAVE DRUG X THAT IS POTENTIAL BENEFIT IF WE KNOW YOU HAVE LESION Y BUT THOSE ARE A SMALL MINORITY RIGHT NOW. BUT I DO THINK THERE HAS TO BE -- I FULLY AGREE WITH ALL MY COLLEAGUES, THERE HAS TO BE A SHIFT IN WHAT WE ARE CONSIDERING THE MAGNITUDE OF RISK. AND WHAT WE'RE CONSIDERING THE PROSPECT OF BENEFIT. I DO THINK WITH BETTER TRIAL DESIGNS, WHERE WE CAN OFFER THIS BUT ULTIMATELY WHAT IT WILL TAKE IS YOU HAVE TO HAVE A PORTFOLIO OF DRUGS THAT YOU CAN SELECT FROM. AND OUR PORTFOLIO IS TERRIBLE. WE HAVE SOME. BUT WE'RE TOO LIMITED. IT'S A COMPLEX PROBLEM BUT RISK AVERSION FROM BIOPSY IS AN OVERCOMABLE ONE IF WE PUT IN CONTEXT OF DIRECT BENEFIT BECAUSE NOW AT LEAST WE HAVE A SMALL PORTFOLIO. OF DRUGS THAT COULD BE RATIONALLY APPLIED AS OPPOSED TO RANDOMLY APPLIED. >> PETER, WE RAN INTO A SITUATION WHERE WE WERE LOOKING AT OUR RESEARCH PROJECT INVOLVING DIPG WHERE ROUTINELY THERE WAS LITTLE DONE FOR THOSE KIDS. INTERVENTIONS WEREN'T USEFUL, RADIATION WAS KIND OF THE TREATMENT AND A GROUP OF PARENTS GOT TOGETHER AND SAID UNTIL WE DEVELOP CELL LINES AND MODELS WE WON'T FIND DRUGS TO TACKLE THIS THING. HOW DID THEY GET AROUND THE ISSUE WHERE THEY ENABLE PEOPLE TO GET TISSUE TO DEVELOP CELL LINES FOR THOSE KIDS WITHOUT THAT DIRECT BENEFIT PER SE? WHAT THIGH EAR DOING IS CREATING WELL CHARACTERIZE MODELS SO HUNT FOR DRUGS IN THE -- HOW -- >> OTHERS MAY KNOW THE HISTORY BEHIND THAT, SOME OF THOSE CAME POSTMORTEM AND THAN P SAY'S ORGANIZATION AND OTHERS HELPD SPEARHEAD OBTAINING POSTMORTEM TISSUE. IN FRANCE THEY HAVE INCREASING EXPERIENCE BIOPSYING PATIENT SAFELY. PART OF THAT STILL HAS TO BE WHAT WOULD YOU DO DIFFERENTLY. UNDER FEDERAL REGULATIONS, IF THAT INFORMATION IS NOT GOING TO IN SOME WAY IMPACT WHAT YOU DO FOR THAT CHILD, YOU'RE NOT GOING TO BE ABLE TO DO THAT. THAT MAY CHANGE BUT MOST CELL LINES LIKELY CAME FROM POSTMORTEM >> RIGHT. THERE'S SOME DEPG. THE LANDSCAPE CHANGING, UNDERGO RESECTION WHERE THERE'S BENEFIT YOU GET IT THAT WAY. BUT STRAIGHT FORWARD BIOPSY WHERE WE JUST WANT TO STUDY IT I THINK IS GOING TO BE A CHALLENGE. >> SO LET ME JUST COMMENT, I THINK PETER DESCRIBED THE SITUATION WELL. I CERTAINLY WOULD NEVER ADVOCATE, THOUGH I WOULD LOVE MORE BIOPSIES TO DO MY OWN RESEARCH, I WOULD NEVER ADVOCATE FOR THAT ON A CLINICAL STUDY. BUT LET ME GIVE YOU THE SCENARIO WHAT HAPPENED WITH BRAF INHIBITOR, IN MELANOMA. WE HAVE TO BROADEN DIRECT BENEFIT A LITTLE BIT FURTHER. SO IN A VERY RARE SITUATION, 50% MELANOMAS HAVE A SPECIFIC MUTATION IN THIS GENE CALLED BRAF. THEY VIRTUALLY ALL RESPOND TO THIS DRUG. BUT ALMOST NO ONE RESPONDS FOR MORE THAN EIGHT MONTHS SO THEY GET THE DRUG AND THEY HAVE THIS BEAUTIFUL RESPONSE AND THEN IT ALL THE TUMOR COMES RARE AND BACK. MELANOMA WAS EASY TO STUDY BECAUSE THEY'RE CUTANEOUS LESIONS. SO WITHIN SIX MONTHS OF ALL THIS HAPPENING, BECAUSE PATIENTS BYE-BYE I DON'T KNOW SAID WHERE THEY RECURRED WE IDENTIFIED THREE PATHWAYS IN THE SETTING OF INHIBITING BRAF, TWO OR THREE OTHER PATHWAYS GOT ACTIVATED WHICH IS EXPECTED TO CAUSE RESISTANCE BECAUSE THEY OCCUR DOWNSTREAM. WE WITHIN A SHORT PERIOD OF TIME HAVE COMBINATIONS AND ACTUALLY COULD EVEN HAVE PREDICTED THAT YOU MIGHT WANT TO WHEN SOMEONE RECURS NOT STOP THE DRUG BUT ADD A SECOND DRUG OR MAYBE A THIRD DRUG. THAT'S BACK TO MY ISSUE ABOUT COMBINATION. SO SHORTLY WE SHOULD BE ABLE TO HAVE -- AND REMEMBER MOST OF THE CASES OF THESE PHASE 1 STUDIES THE RESPONSE RATES ARE MUCH LESS THAN -- THEY'RE LESS THAN 50%. BUT IF WE BIOPSY A PATIENT, A CHILD SEE WHY THEY RESPONDED AND RECUR HAVE SOME INFORMATION ABOUT WHAT IS LEADING TO THAT RESISTANCE, WE CAN CONTEMPLATE ADDING ANOTHER DRUG AND WE CAN DESIGN PROSPECTIVE STUDIES TO DO THAT OR SWITCHING THERAPY ALL TOGETHER. THE OTHER AREA THAT I'M CURIOUS WHAT PEOPLE THINK, I HAVE HAD MANY DISCUSSIONS, BUT HAVING BEFORE INVOLVED IN STUDIES WHERE YOU SEE FIRST OF ALL WHEN I STARTED, PETER, YOU CAN VERIFY THIS, OVERALL RESPONSE RATES IN PHASE 1 CLINICAL TRIALS WERE ABOUT 5% OR LOWER. WE SEE MUCH HIGHER RESPONSE RATES NOW BECAUSE WE'RE A LITTLE BIT SMARTER. BUT NUMBERS, WE DID PHASE 1 STUDIES IN FEED WHEREIA TRICK PATIENT THOSE THE EXPECTED BENEFIT WAS LESS THAN 5%. SOMEHOW WE DID. NOW IT'S PROBABLY HIGHER THAN THAT BUT IT'S -- IT CAN'T BE MUCH MORE THAN 25%. SO MOST OF THE TIME WHEN WE PUT A CHILD ON A PHASE 1 STUDY UNFORTUNATELY THEY'RE DOING TO DIE OF THEIR DISEASE. THEIR PARENTS KNOW THEY'RE PARTICIPATING IN RESEARCH. SO IF WE RUN STUDIES AND FIND 10% RESPONSE RATE AND AT THE END OF THE DAY HAVE NO MORE INFORMATION THAN THAT, I THINK WE HAVE DONE A DISSERVICE TO THOSE FAMILIES. WE ARE OBLIGATED TO GET MORE THAN A 10% RESPONSE RATE. I THINK WE CAN DO IT SAFELY, IT'S UNETHICAL NOT TO DO THAT. BUT THAT'S -- I FEEL PASSIONATELY ABOUT THAT BUT I DON'T KNOW WHAT THE ADVOCACY COMMUNITY FEELS. >> I CAN MAKE ANTIREJECTION AT THIS POINT BECAUSE I ABSOLUTELY AGREE. ONE AREA AS ADVOCATE I SEE CONCERN THAT OFTENTIMES YOU WILL SEE A DRUG DEVELOPED FOR ADULT INDICATION MOVED TO PHASE 2 OR EVEN PHASE 3 TRIAL AS COMBINATION THERAPY, VERY EFFECTIVE WITH LOW TOXICITY. IN THESE INSTANCES WHY NOT DO THE PHASE 1 COMBINATION THERAPY FOR CHILDREN TO GIVE THEM A CHANCE OF SURVIVAL. WHEN THERE'S LOW TOXICITY, SIGNIFICANT INCREASED EFFICACY, ON COMBINATION. >> I WOULD LOVE TO HEAR GREG'S COMMENT ON THIS BECAUSE WE'RE REALLY -- WE'RE RUNNING A TRIAL NOW STRUGGLING WITH THIS, WHAT DO YOU DO WHEN THERE'S NO PEDIATRIC PHASE 1 DATA. AND WE'RE TRYING TO DESIGN THIS BY HAVING A BRIEF DOSE FINDING, AND THEN AUTOMATICALLY INTO THE PHASE -- COMBINATION. BUT IT GETS TRICKY WHEN -- AND THERE IS A LARGE EXPERIENCE THAT THERE ARE UNANTICIPATED TOXICITIES SOMETIMES WHEN TARGETING THESE -- COMBINE TARGETED AGENTS SO I AGREE COMPLETELY BUT WE NEED TO WORK WITH THE FDA ON INNOVATIVE SOLUTIONS. >> I THINK THOSE INNOVATIVE SOLUTIONS -- GO AHEAD. >> ONE QUICK INTERSECTION. BEFORE YOU MAKE YOUR COMMENTS. AS A PARENT I UNDERSTAND THERE ARE THESE RISKS OF SIGNIFICANT INCREASED TOXICITIES. I WOULD BEEN WILLING TO ASSUME THEM FOR INCREASED POSSIBILITY OF A GOOD OUTCOME. >> SO I THINK THERE ARE NO REAL BARRIERS, IF YOU WILL, TO NOT HAVING PEDIATRIC PHASE 1 DATA. I THINK THIS IS SOMETHING THE AGENCY HAS GONE ON RECORD BEFORE AND AN APPROPRIATE SITUATIONS AND APPROPRIATE CASES. PART OF IT WOULD DEPEND ON THE TOTAL BODY OF EVIDENCE THAT EXISTS WITH RESPECT TO THE DRUGS SAFETY IN AN ADULT POPULATION. AND WHAT CLINICAL BIOLOGIC RATIONALE IS FOR USING IT IN COMBINATION. SO WE'RE CERTAINLY PREPARED AND P WE HAVE APPROVED DRUGS THAT THERE'S BEEN NO ADULT PHASE 1 TESTING, NO PK STUDIES DONE IN ADULTS. (INDISCERNIBLE) WAS APPROVED FOR CHILDREN AND THERE WAS LITTLE OR NO ADULT DATA THAT PRECEDED THAT. SO IT'S POSSIBLE. IT'S POSSIBLE. >> MAYBE I CAN ADD. FIRST OF ALL, I THINK THE COG STUDY (INDISCERNIBLE) HOPEFULLY WILL BE AN EXAMPLE. IF THERE'S NOT A PHASE 1 STUDY IN PEDIATRIC WITH BIOMARIN COMPOUND, WE HAVE HOPE OUR STUDY IS APPROVED BUT WE ONLY GO DOWN TO 13 SO WE'RE EASIER. BUT I HOPE THERE WILL START TO BE EXAMPLES AND CERTAINLY, I WOULD JUST ADD TO WHAT GREG SAID, IT'S NOT -- PEOPLE ASSUME IT'S THE REGULATORS, IT'S FDA BECAUSE IT'S EASIER TO -- BUT I WILL TELL YOU, WE GET SEDUCED BY OUR PHARMA PARTNERS AND THEY WANT TO GET A DRUG APPROVED. AND THEY WANT TO GET THEIR DRUG APPROVED AS A SINGLE AGENT, I OOH CLEAN, THEY SHOW, HERE IS A RESPONSE AND WE GET ALL HUNG UP IN THIS. WE GET STUCK IN THIS GETTING THIS SINGLE DRUG APPROVED OPPOSED TO REALIZING WE DON'T NEED TO GET SINGLE DRUG APPROVED. WE NEED TO FIGURE OUT HOW TO GET IT INTO COMBINATIONS QUICKER. IT -- NOT JUST THE FDA. SOMETIMES PHARMA DOESN'T WANT TO HAVE THE DISCUSSION WITH THE FDA BECAUSE THEY WANT THE SINGLE DRUG APPROVED AS QUICKLY AS POSSIBLE. THOUGH IT WILL TAKE MUCH MORE PATIENTS TO NOT GIVE THEY WILL A CHANCE TO CURE, AS YOU SAY. AND GET MORGUE QUICKLY TO COMBINATIONS. >> I WANTED TO ALSO AS FAR AS PEDIATRIC PHASE 1 DATA, THERE ARE NOW PUBLICATION FROM THE CLINICAL PHARMACOLOGY GROUP AT THE FDA. LOOKING AT ADOLESCENCE, CHILDREN BETWEEN AGE 12 AND 18. AND LOOKING AT PK OVER 500 DRUGS EVALUATED AS PART OF THE BPCA. AND THE DIFFERENCES IN PK BETWEEN ADOLESCENTS AND ADULTS WHERE NEGLIGIBLE AND VIRTUALLY ALL CASES NON-EXISTENT. SO OUR REQUIREMENT FOR ENROLLING PATIENTS ONLY AFTER THE AGE OF 16, 17, 18, WHEN SOME OF THESE ADOLESCENTS ACTUALLY HAVE DISEASES LIKE MELANOMA, THAT OCCUR AT A YOUNGER AGE I THINK IS SOMETHING THAT CAN BE, SHOULD BE CHANGED. THE SAME IS TRUE FOR SOME OF THE TRIALS IN OSTEOSARCOMA THAT ARE BEING DEVELOPED CURRENTLY THAT ARE EXCLUDING PATIENTS UNDER THE AGE OF 18 I SEE NO REASON FOR THAT. THERE IS NO REQUIREMENT, IF THERE ARE REASONS TO ENROLL YOUNGER CHILDREN, CONSULTS COULD BE REQUESTED. THERE IS PLENTY OF INTEREST IN FLEXIBILITY ON THE AGENCY'S PART. >> I WOULD LIKE TO THANK ALL OUR PRESENTERS AND THE OTHER PARTICIPANTS, THIS WAS JUST A TERRIFIC INTRODUCTION TO SET THE STAGE FOR THE REST OF THE DAY. WITH THAT I'M GOING TO DECLARE A SHORT TIME OUT. YES. >> DR. HELMAN, DOESN'T THE FEDERAL REGISTER ALLOW PARENTS TO CONSENT TO HAVING A BIOPSY? I CAN'T IMAGINE IF THERE'S AN 18 -- UNDER 18 YEARS OLD THE PARENT NOTWITHSTANDING ALL THE OTHER PIECES OF THE FEDERAL REGISTER CAN'T SAY WE CONSENT OR 18, 19-YEAR-OLD CHILD WHO DOES HAVE MAJORITY WHY COULDN'T THEY CONSENT. >> YOU CAN -- WE HAVE WHAT'S CALLED ASSENT, WE HAVE PATIENTS THAT ARE OLD ENOUGH BUT UNDER 18 TO GIVE ASSENT. AND THE PARENT CONSENTS BUT THERE'S A DIFFERENCE BETWEEN BEING ABLE TO GIVE CONSENT AND GETTING A STUDY APPROVED WHERE YOU MANDATE THAT'S WHERE THE IRB HAS THE RESPONSIBILITY TO MAKE SURE THAT THERE IS SOME POTENTIAL FOR BENEFIT. I THINK THE SQUIGGLY SQUISHY PART IS HOW TO DEFINE POTENTIAL FOR BENEFIT. IF THERE'S NO POTENTIALK IF WE'RE DOING IT SO I CAN WRITE A GRANT. THERE'S NO POTENTIAL FOR BENEFIT, THAT'S MORE DIFFICULT. SO IT'S NOT THE PARENT CAN'T CONSENT, WE CAN'T GET PROTOCOLS APPROVED IN CERTAIN INSTANCES BECAUSE THE IRBs ARE CONCERNED ABOUT COERCION OR I CAN TALK FOR AN HOUR ABOUT COERCION WHICH IS ALSO AN OVERPLAYED PART. BUT THOSE ARE THE ISSUES. SO SINCE YOU BROUGHT IT UP, THAT'S ONE OF THE FAVORITE THINGS THAT THE IRBS SAY, IT'S COERCESIVE AND THEY FEEL THEY WON'T GET THE EXPERIMENTAL THERAPY IF THEY DON'T CONSENT TO HAVE A BIOPSY. WELL, YOU KNOW, AGAIN, I HAVE BEEN IN THIS FIELD 30 YEARS, IN THE OLD DAYS, WE ONLY HAD ONE DRUG. WE ONLY HAD ONE APPROACH. BUT WHEN WE'RE TALKING NOW, WHEN I'M CONSENTING A PATIENT FOR AN EXPERIMENTAL THERAPY, THERE'S THREE OR FOUR OTHER OPTIONS SO IT'S NOT AS IF WE KNOW WHAT WE'RE GOING TO DO IS BETTER, USUALLY HAVE OTHER OPTIONS ANYWAY, SO O COERCION IS NOT THE WRIGHT WORD ANYMORE. WE ARE USED TO IT WHEN THERE WERE NO OTHER ALTERNATIVES OTHER THAN THE COG STUDIES FOR NEWLY DIAGNOSED EWING'S SARCOMA BUT THAT'S NOT THE CASE ANY MORE SO COERCION MAYBE SOMETHING OUR ADVOCATES COULD HELP TEACH OUR IRBs, WE ALWAYS HAVE PATIENT REPRESENTATIVES ON THE IRBs, WE NEED TOY GUSH OUT HOW TO DO THIS -- TO FIGURE OUT THOUSAND DO IN A WAY DIFFERENT FROM THE 1960s. (OFF MIC) >> -- TO ADVOCATE FOR THIS CAUSE, BUT I HAVE TO KNOW WHO TO ADVOCATE AND WHAT TO SAY, ET CETERA. >> IF I COULD MAKE A COMMENT HERE. I HAVE GONE TO A COUPLE OF IRBs AND SPOKEN TO THEM AS A PARENT. IN BOTH INSTANCES, THERE WERE INCREDIBLY UNCOMFORTABLE MEETINGS FOR THE IRB, BECAUSE I HAVE NEVER MET A PARENT BEFORE WHO HAD COME TO TALK ABOUT THIS ISSUE. AND THEIR VIEWS CHANGED VERY QUICKLY. I WOULD FRANKLY COUNCIL ADVOCATES AND CLINICS TO PAIR UP AND GO TALK TO IRBs. I THINK THAT IT'S REALLY EASY WAY TO MOVE THE NEEDLE. >> I'M AFRAID I'M GOING TO HAVE TO BE A RUDE CHAIR AND AT LEAST CALL A SHORT ADJOURNMENT BECAUSE WE WANT TO KEEP THE MEETING ON TIME AND WE HAVE OTHER PEOPLE READY TO SPEAK AT LUNCH AND PEOPLE HAVE TO BE ABLE TO TAKE A BREAK AN P GET THEIR FOOD ESPECIALLY ANYBODY WHO DIDN'T ORDER THEIR FOOD HAS TO GO DOWNSTAIRS. SO IF THERE ARE PEOPLE THAT WANT TO TALK TO FOLKS DURING THE BREAK, THAT WOULD BE GREAT BUT IN ORDER TO KEEP THE MEETING IN LINE SO WE CAN RESTART IN LESS THAN 20 MINUTES, I'M GOING TO DECLARE A SHORT RECESS AND WE'LL COME BACK BY NOON. WHEN WE LAST SPOKE, 15 MINUTES AGO, I USED CHAIR PREROGATIVE TO GET A CHANCE TO SEND EVERYBODY TO THE CAFETERIA BUT I CUT OFF GAVIN LINDBURG WHO WAS INTERESTED IN ASKING A QUESTION TO THE PEOPLE WHO PRESENTED IMMEDIATELY BEFORE. SO WHILE WE GATHER OTHER FOLKS, GAVIN, WOULD YOU LIKE TO ASK YOUR QUESTION? WE HAVE YOUR ASSEMBLED SPEAKERS HERE. >> THANK YOU VERY MUCH. I APPRECIATE YOUR PATIENCE WITH ME. INVESTMENT IN PEDIATRIC CANCER RESEARCH IS APPROXIMATELY 200 MILLION DOLLARS A YEAR. I HAVE BEEN IN THE COMMUNITY FOR ABOUT EIGHT YEARS NOW AND I THINK THAT NUMBER HAS BEEN PRETTY STAGNANT FOR THAT PERIOD OF TIME. THE OTHER COMMENT THAT WAS STRIKING WAS AN OBSERVATION THAT THERE WERE CONVERSATIONS WITH THREE PARENTS THIS WEEK AND COULDN'T FIND A CLINICAL TRIAL THAT WAS OPEN. MY QUESTION IS, WHAT ARE YOUR THOUGHTS. AND SINCE WE HAVE THESE AT VO KAATZ IN THE ROOM, WHAT COULD WE DO TO RAISE THE PROFILE WITH THESE IMPORTANT ISSUES WITH THE INSTITUTE? THANK YOU. >> BEFORE WE GO TOO DEEPLY DOWN THAT PATH, I WOULD ALSO POINT TO THE FACT THAT WE HAVE A PANEL LATER IN THE AFTERNOON THAT REALLY FOCUSES ON SPECIFICALLY WHAT CAN WE DO THROUGH ADVOCACY. SO JUST KEEP THAT IN MIND. I DON'T MEAN TO CUT OFF THE ANSWER HERE. >> THANK YOU FOR THE QUESTION, GAVIN, AND I ALLUDED TO THE INVESTMENT. IT'S EASY TO SAY NOT NEARLY ENOUGH AND WE NEED MORE FUNDING, BUT I THINK THAT THE RESPONSIBILITY IS ALSO ON US TO COME UP WITH THE RIGHT IDEAS WORTHY OF FUNDING. AND THAT IS WHY I'M A BIG ADVOCATE FOR THINGS LIKE THE PPTP, WHERE THERE IS A MUTUAL GOAL WHERE THERE IS A CLEAR WIN WIN FOR THE NCI AND FOR THE COMMUNITY. I THINK WE NEED A LOT MORE OF THOSE TARGETED APPROACHES FOR DEVELOPING DRUGS IN A FASTER WAY. WE ARE DOING NOTHING IN HIGH-THROUGHPUT COMBINATORIAL SCREENING, HAPPENING VERY COMMONLY IN ADULT CANCER. >> SO, I GUESS I WOULD SAY, OBVIOUSLY, WE NEED MORE FUNDING. NO QUESTION ABOUT THAT. I REMEMBER HAVINGA CONVERSATION WITH A CONGRESSMAN A COUPLE OF YEARS AGO WHO WAS SORT OF ADVOCATING AT THE TIME FOR INCREASING PEDIATRIC CANCER RESEARCH WHILE VOTING TO DECREASE NIH FUNDING. AND THAT WON'T WORK. SO, I THINK WHAT WE NEED ARE ADVOCATES TO DO IS KEEP THE PRESSURE ON OUR CONGRESS, THAT CUTTING THE NIH IN THIS TIME OF UNPRECEDENTED OPPORTUNITY, PERIOD, IS A BAD IDEA. AND THEN I WOULD SAY, IF YOU REMEMBER MALCOLM SMITH MADE A COMMENT. HE DIDN'T FOCUS ON IT YOU ABOUT HE MADE A COMMENT ABOUT, WE NEED TO BE MORE RIGOROUS IN NOT WASTING TIME DOING THINGS THAT AREN'T GOING TO ULTIMATELY CHANGE THE OUTCOME OF PATIENTS. AND IT HURTS ME EVERY TIME WE SPEND MONEY ON THINGS THAT AREN'T REALLY THE MOST OUTSTANDING, RIGOROUS SCIENCE, EITHER IN THE BASIC FIELD OR IN THE TRANSLATIONAL AND CLINICAL FIELD. AND I THINK WE NEED MORE MONEY, BUT I ALSO THINK WE COULD STILL SPEND OUR MONEY MORE WISELY. AND I COME BACK TO, DURING A CLINICAL TRIAL WHERE WE JUST GET THE ANSWER, THIS DRUG IS ACTIVE OR NOT, I DON'T THINK IS GOOD ENOUGH IN 2014. AND I THINK WE NEED TO MAKE SURE THAT WE SPEND OUR OR WE GET THE MOST BANG FOR THE BUCK. AND WE NEED MORE BUCK, BOTH. >> ALL RIGHT. WHAT WE SCHEDULED FOR -- >> JUST MY ECHO. >> YES, I DIDN'T SEE. >> I WANT TO ECHO LEE'S COMMENT THAT WE DO NEED NIH FUNDING T IS CRITICAL. WE ARE NOT GOING TO RISE IMMENSELY WITHOUT MAINTAINING, INCREASING NIH FUNDING. I THINK JOHN MADE A GREAT POINT AS WELL. THISINS INSTITUTE DRIVEN BY SCIENCE AND SO I THINK TO POINT WHAT THE BEST SCIENCE IS, IT'S NOT BEING DONE, WORK THAT IS CRITICAL AND IS JUST THE HIGHEST SCIENTIFIC QUALITY NOT BEING DONE, THOSE REALLY POINTING TO SCIENCE IS GOING TO, IN THE SCIENTIFIC GAPS AND HOW THERE IS COMPELLING RESEARCH THAT CAN ADDRESS THOSE GAPS, WILL GIVE US OUR BEST CHANCE OF GETTING MORE FUNDING FOR SPECIFIC THINGS. >> THANK YOU. WE ARE GOING TO MOVE TO A WORKING LUNCH, BECAUSE WE NEEDED TO GIVE YOU A CHANCE TO EAT. BUT IT IS GOING TO BE A MODERATED DISCUSSION WITH DR. PETER ADAMSON PRESENTING, NANCY GOODMAN, AND GREG REAMAN. I ASKED LEE TO HELP ON THE MODERATION BECAUSE THIS IS HIS SPACE AND KNOWS ITEL, BUT ALSO DAVID ARONS, ONE OF OUR PANEL MEMBERS, WHO HAS DONE A LOT OF PREPATORY WORK ON THIS AND HIS ORGANIZATION, NATIONAL BRAIN TUMOR SOCIETY. I GOT HIM INTO A ROLE OF SERVING AS A MODERATOR IN THIS. SO PETER, WOULD YOU LIKE TO START? >> I DON'T HAVE SLIDES. SO FIRST OF ALL, THANK YOU FOR INVITING ME AND FOR HAVING THIS SESSION. I WANT TO CHANGE THE DIALOGUE A LITTLE BIT AND I DON'T HAVE SLIDES IN PARTICULAR BECAUSE I WANTED TO GET A SENSE OF WHAT WE WANT TO ACHIEVE FOR THIS MISSION. THE MOST IMPORTANT TAKEHOME MESSAGE FOR MEMBERS OF THIS COMMITTEE IS THAT THE PROBLEM OF CHILDHOOD CANCER HAS NOT BEEN SOLVED. AND I THINK UNDERSTANDING THAT -- THIS MORNING MY FRIENDS AND COLLEAGUES PRESENTED A TREMENDOUS BACKGROUND ABOUT ALL THE ACTIVITY. BUT, HOPEFULLY, WHEN YOU LEAVE HERE, YOU ALSO WILL BE OUTRAGED. AND THE REASON YOU NEED TO BE OUTRAGED, THE REASONS ARE SEVERAL-FOLD. CHILDHOOD CANCER REMAINS A LEADING CAUSE OF DEATH FROM DISEASE IN THIS COUNTRY. THE LEADING CAUSE OF DEATH FROM DISEASE IN THIS COUNTRY. ALL THE IMPRESSIVE ACCOMPLISHMENTS WE HAD, THAT'S A FACT. THAT'S A FACT THAT SHOULD BE FRONT AND CENTER. BUT MORE IMPORTANTLY, AND JOHN PRESENTED SOME OF THIS DATA, BUT LET ME REFRAME IT. WHAT WE PUT OUR CHILDREN THROUGH TO ACHIEVE A CURE IS UNACCEPTABLE. WHAT DO I MEAN BY THAT? IF YOU LOOK AT TREATMENT FOR HIGH-RISK CANCERS, TO BE HIGH-RISK LEUKEMIA, HIGH-RISK NEUROBLASTOMA, HIGH-RISK BRAIN TUMORS. GO DOWN THE LINE. IF YOU LOOK AT WHAT WE PUT OUR CHILDREN THROUGH, 4-5 CHILDREN DURING TREATMENT EXPERIENCE SEVERE LIFE-THREATENING OR FATAL TOXICITY. 4-5 CHILDREN! WE HAVE GOTTEN VERY GOOD AT A COMMUNITY OF SPECIALISTS, PEDIATRIC ONCOLOGISTS AND NURSING AND GO DOWN THE LINE, OF SUPPORTING CHILDREN THROUGH THAT. BUT SEVERE LIFE-THREATENING OR FATAL TOXICITY, NOWHERE IN MEDICINE WOULD YOU SEE THAT ALLOWED. THAT IS WHAT WE USE. WE ARE FUNDAMENTALLY STILL USING DRUGS THAT WERE DISCOVERED IN THE 50s AND 60s. THEY ARE GREAT DRUGS AND I WOULD ARGUE THAT MANY OF THEM ARE TARGETED DRUGS AND DIFFERENT TARGETS. BUT THE TOXICITY OF THOSE DRUGS, YES, WE ARE GOOD AT MANAGING THE TOXICITY, BUT THAT'S WHAT WE SPEND OUR DAY DOING. IS MANAGING TOXICITY. AND THEN FOR THOSE CHILDREN WHO WE DO QUOTE/UNQUOTE CURE, ALMOST HALF OF THEM CARRY A LIFELONG BURDEN FROM THEIR CANCER OR TREATMENT. SO WE HAVE NOT SOLVED CHILDHOOD CANCER AND WE HAVE TO CHANGE THE DIALOGUE AND NOT GIVE THE IMPRESSION THAT WE SOLVED IT. THE NUMBERS ARE IMPRESSIVE. YES, WE MADE PROGRESS BUT THIS IS AN ENORMOUS PROBLEM. SO, WITH THAT BACKGROUND, LET ME TALK ABOUT TWO AREAS THAT, ONE WE TOUCHED ON IN SOME REGARD, FUNDING, AND THE OTHER, I'D LIKE TO TALK ABOUT THE REGULATORY ENVIRONMENT. AND THAT SOUNDS REALLY BORING BUT IT IS TURNING OUT AS FAR AS A BARRIER TO DRUG DEVELOPMENT. IN SOME RESPECTS, UNEXPECTED BARRIER. WHEN I TALK ABOUT REGULATORY ENVIRONMENT, I'M TALKING ABOUT THE GLOBAL REGULATORY ENVIRONMENT AND NOT THE FDA. SO, YOU HEARD A LOT ABOUT SOME VERY IMPORTANT PROGRAMS THAT ARE FUNDED BY THE NCI. BUT THERE ARE SOME FACTS THAT I'M SURE FAMILIAR TO MANY IF NOT ALL OF YOU, WHO IS THE MAJOR FUNDER OF BIOMEDICAL RESEARCH IN THIS COUNTRY? SO NIH FUNDS ABOUT 25%. THE PRIVATE SECTORS ARE AROUND 60 PLUS%. FOR PEDIATRIC ONCOLOGY, THROW THAT MATH AWAY. THAT MATH DOESN'T WORK. THE VAST PROPORTION OF FUNDING FOR CHILDHOOD CANCER IS FROM THE NIH. INDUSTRY IS NOT YET REGISTERING ON OUR RADAR SCREEN. IT'S REALLY ALL FUNDED BY THE NIH AND THE REASON IT IS IMPORTANT IS THAT WHEN THE NIH BUDGET GETS CUT, WE DON'T HAVE ANOTHER FUNDING STREAM. WE ARE RELIANT ON THE NIH FUNDING. AND WITHOUT QUESTION, AND YOU'LL HEAR IT FROM EVERYONE, WE HAVE TO INCREASE THE NIH BUDGET. WE KNOW THAT. AND THE IDEA THAT ALL SHIPS RISE, SURE. I AVIBE TO THAT AS WELL. YOU NEVER WANT TO PIT ONE DISEASE AGAINST ANOTHER. BUT I'M GOING TO. AND HERE IS WHY WHY. THERE ARE NEW PROGRAMS GOING TO THAT THE NCI IS FUNDING. MAY HAVE HEARD ABOUT THEAL KEMIST TRIAL. THE NCI MATCH TRIAL. SO THE ALCHEMIST TRIAL, AND I DON'T KNOW THE NUMBERS, BUT 6000 PLUS PATIENTS WITH LUNG CANCER WILL GET SCREENED B450 WILL GET PUT ON A STUDY. THE REST ARE GOING TO BE SEQUENCED AND SO FORTH. VERY INTERESTING TRIAL. MAX TRIAL. THE BASKET STUDY WHERE WE'LL TRY TO ALIGN PATIENTS WITH SPECIFIC MUTATIONS WITH SPECIFIC DRUGS. LOTS AND LOTS OF INITIATIVES THAT MAKE SENSE THAT I THINK PROBABLY, AND LEE TELL ME IF I'M WRONG, TENS OF MILLIONS OF DOLLARS. AND THAT'S A GOOD INVESTMENT. WHAT NEW INITIATIVES, WHAT NEW INITIATIVES HAVE THE NCI FUNDED FOR PEDIATRIC ONCOLOGY? NONE. PEOPLE WORK HARD TO KEEP THE PROGRAMS AT A LEVEL OF FUNDING BUT THERE ARE NO NEW INITIATIVES. WHEN WE TALK ABOUT WE NEED BASKET RULES AND GENOMICS AND SO FORTH, WHO WILL PAY FOR THAT? IT'S NOT GOING TO BE INDUSTRY. SO I THINK THERE IS A PUBLIC RESPONSIBILITY THAT THE NCI HAS AND WE PUT THEM IN IMPOSSIBLE POSITION TO BALANCE ALL THIS AS OUR BUDGET IS CUT. BUT WE CAN'T LET THE PRESSURE OFF BY SAYING WE SHOULD BE DOING MORE GENOMIC. WE SHOULD BE DOING MORE THIS AND THERE BE NO FUNDING FOR IT. IT IS AN ISSUE. IT'S A SMALL SLICE OF THE BUDGET AND RESEARCH FOR CHILDHOOD CANCER IS ENTIRELY DEPENDENT ON THAT FUNDING STREAM AND THAT IS NOT TRUE FOR THE REST OF CANCER. IT IS ENTIRELY DEPENDENT ON THE NCI FUNDING SCREAM WHEREAS 60% OF FUNDS IN BIOMEDICAL RESEARCH AND ADULT PATIENTS WITH CANCER IS NOT DEPENT ENT ON THAT. SO THAT, I THINK IS A MESSAGE THAT SHOULDN'T BE LOST ON THIS COMMITTEE AS IT ADVOCATES. AND HOW YOU DO THAT EFFECTIVELY, YES, RACES THE BUDGET. WE VALUES TO POINT OUT THAT PEDIATRICS ONCOLOGY IS ENTIRELY DEPENDENT ON IT. SO THE LAST FEW MINUTES I'M GOING TO TALK ABOUT. >> SO WE HEARD FROM JOHN 48% OF HIS BUDGET -- >> AND I WOULD SAY THAT JOHN IS AN EXTRAORDINARY SCIENTIST WITH AN EXTRAORDINARY LAB AND I CAN TELL YOU THE REST OF THE COUNTRY DOES NOT HAVE 60% FUNDS FLOWING FROM INDUSTRY FOR THEIR WORK. BUT THE REST OF THE COUNTRY IS NOT LIKE JOHN. AND I DON'T THINK JOHN -- >> BUT. MAYBE WE DON'T WANT NONEXTRAORDINARY SCIENTISTS GETTING FUNDING IF -- YOU KNOW? JUST WANT TO PLAY BOTH SIDES OF THAT. >> OKAY. WELL, THIS IS AN ARGUMENT -- YOU'RE GOING TO LOSE THIS ARGUMENT. SO I'M NOT EVEN UPON GOING TO PURSUE IT. I'M NOT SAYING WE SHOULDN'T FUND -- OR ONLY FUND THE BEST, BUT I THINK IT IS FAIR TO SAY THAT INDUSTRY'S FISCAL FOOTPRINT IN PEDIATRIC ONCOLOGY IS A TINY FRACTION OF THEIR FISCAL FOOTPRINT IN THE REST OF ONCOLOGY. AND THAT MODEL IS NOT GOING TO CHANGE. NANCY IS GOING TO TELL YOU ABOUT AN EXTRAORDINARY EFFORT THAT SHE HAS HELPED SPEARHEAD FOR CREATING HOPE ACT, THAT WILL TRY TO CHANGE THAT DIALOGUE, BUT IT TAKES EXTRAORDINARY EFFORTS TO CHANGE THAT DIALOGUE. LET ME TALK ABOUT THE GLOBAL REGULATORY ENVIRONMENT. SO IN THE U.S., THERE WERE TWO INITIATIVES AND YOU'RE PROBABLY FAMILIAR WITH THEM. AND GREG, HOPEFULLY, I DON'T KNOW HOW MUCH OF BPCA YOU WANT TO TALK ABOUT -- >> A LOT. >> SO I'LL BE BRIEF. BEST PHARMACEUTICALS FOR CHILDREN ACT, GREG WILL TELL BUT THIS. AND FOR PEDIATRICS, THEY HAD IN MANY AREAS, A MAJOR IMPACT. THEY HAD A MORE MODEST IMPACT FOR CHILDHOOD CANCER BUT THOSE CLEARLY HAVE CHANGED THE LANDSCAPE 234 THIS COUNTRY. IN EUROPE -- IN THIS COUNTRY. IN EUROPE, THE E MORE. A -- THE EMA PUT FORWARD LEGISLATION THAT BORROWED SOME PARTS OF THE EXPERIENCE IN THIS COUNTRY AND CREATED THEIR VERSION. AND THE OUTPUT OF THAT IS CALLED THE PEDIATRIC INVESTIGATION PLAN OR PIPS. FOR CHILDHOOD CANCER, ADVOCACY NEEDS TO BECOME MORE GLOBAL, BAYS WHAT HAPPENS IN EUROPE WILL IMPACT CHILDREN IN THIS COUNTRY AND VICE VERSA. YOU HEARD ABOUT DIMINISHING -- AS WE TAKE SMALL POPULATIONS AND STUDY SMALLER SUBSETS, WE HAVE TO BECOME INCREASINGLY GLOBAL SO ADVOCACY ACTUALLY HAS TO BECOME INCREASINGLY GLOBAL WHEN IT COMES TO CHILDHOOD CANCER. SO, THE PIPs, PEDIATRIC INVESTIGATION PLAN. WELL INTENDED BUT SIGNIFICANT UNINTENDED CONSEQUENCES. WHAT THE PIP REQUIRES INDUSTRY SPONSORS TO DO IS HAVE A FULL DEVELOPMENT PLAN, PHASE I, PHASE II, PHASE III APPROVED BEFORE THEY'LL GET MARKETING AUTHORIZATION. THE PROBLEM IN ADDITION TO THE ONE MALCOLM SPOKE ABOUT WHERE WE ARE TAKING A DRUGCENTRIC VIEW OF CANCER TREATMENT AS OPPOSED TO A DISEASE OR PATIENT-CENTRIC VIEW. THE OTHER PROBLEM WITH THAT IS IT IS AN ENORMOUS DRAIN OF RESOURCEOS EVERYONE'S PART TO PRETEND WE KNOW WHAT A TRIAL WILL LOOK LIKE THAT MIGHT GET CONDUCTED 15 YEARS FROM NOW BEFORE A DRUG HAS EVER BEEN GIVEN TO A CHILD. SO, PEOPLE ARE RUNNING IN CIRCLES COMING UP WITH PLANS FOR THEIR DRUG, PHASE I, PHASE II, PHASE III, WHEN WE KNOW NOTHING ABOUT THE DRUG IN THE PEDIATRIC SETTING. SO THE UNINTENDED CONSEQUENCE IS THAT IN MANY CIRCUMSTANCES, THE REGULATIONS TO STIMULATE PEDIATRIC DRUG DEVELOPMENT ARE DELAYING INITIATION OF CLINICAL TRIALS IN THIS COUNTRY. THE REASON THAT IS HAPPENING IS -- AND I'LL GIVE YOU AN EXAMPLE. I WON'T NAME THE COMPANY. WE HAVE A TRIAL THAT WAS READY TO GO THREE YEARS AGO, AND IT WAS ABOUT AS STRAIGHTFORWARD A TRIAL AS WE COULD HOPE. IT WAS NOT NEARLY AS SOPHISTICATED AS WHERE WE WANT TO BE WITH COMBINING DRUGS. I MEAN, THIS WAS ABOUT AS SIMPLE AS IT COULD GET. BUT THEY DID NOT HAVE 69 OFF ON THEIR PEDIATRIC INVESTIGATION PLAN. AND WHEN THEY DID HAVE THE SIGNOFFS, A GREAT DEAL OF FOCUS WAS PUT ON, HOW ARE YOU GOING TO DOSE CHILDREN LESS THAN TWO? THAT'S NOT TO MINIMIZE THE IMPORTANCE OF DOSING CHILDREN LESS THAN TWO, BUT WE ARE INTERESTED IN TUMORS THAT OCCURRED IN ADOLESCENCE. FOR THREE YEARS, THAT TRIAL HAS BEEN ON HOLD WHILE WE FIGURE THIS OUT IT'S AN UNINTENDED CONSEQUENCE. SO, WE NEED THE ADVOCACY COMMUNITY TO COALESCE AROUND ISSUES THAT IMPACT CHILDREN WITH CANCER NOT JUST IN THIS COUNTRY, BUT ACTUALLY OVER SEAS AS WELL WHERE THERE HAS TO BE A BETTER HARMONIZATION BEHIND REGULATORY REQUIREMENTS AND INCENTIVES ACROSS THE GLOBE. THERE IS DIALOGUE BETWEEN THE FDA AND THE EMA, BUT TO BE VERY BLUNT, THE EMA COMPLETELY TRUMPS, IN MY VIEW FOR CHILDHOOD CANCER, COMPLETELY TRUMPS ANYTHING WE HAVE ON THE REGULATORY SIDE IN THIS COUNTRY. IN THE U.S. FOR CANCER DRUGS IT'S VOLUNTARY. REQUIREMENTS WILL ALWAYS TRUMP VOLUNTARY WITH INCENTIVE. AND THAT IS THE REAL PROBLEM. SO, I'M GOING TO PAUSE THERE AND I THINK GREG WILL PROBABLY COUNTER SOME OF THOSE ARGUMENTS, BUT THE MAIN MESSAGE AGAIN, WE HAVEN'T SOLVED THIS. WE ARE MORE DEPENDENT ON NCI FUNDING BECAUSE IT IS IN LARGE MEASURE OUR ONLY FUNDING STREAM. PHILANTHROPY UNQUESTIONABLY INCREASED BUT FOR CHILDHOOD CANCER IS STILL WITH ONE EXCEPTION, A RELATIVELY SMALL ENTERPRISE. AND INDUSTRY, ALTHOUGH THEY ARE INVESTING MONEY, IT IS STILL A SMALL INVESTMENT AND IT IS FOCUSED VERY MUCH ON PRIORITIZING, AS IT OUGHT TO BE, PRIORITIZING THEIR PLAN AND NOT NECESSARILY DISCOVERY RESEARCH. SO I'LL PAUSE THERE AND I DON'T KNOW IF YOU WANT LEE TO DO QUESTIONS AT THE END. THAT MIGHT BE BETTER. >> I THINK WE SHOULD DO WHAT WE DID LAST TIME IF THERE ARE ONE OR TWO SPECIFIC QUESTIONS AND THEN WE'LL GET THE OTHER MEMBERS TO PRESENT AND HAVE A BROADER DISCUSSION. IF THERE ARE ONE OR TWO BURNING QUESTIONS -- >> CONSIDER ME AS THE NEWCOMER MORE LIKE THE SIMPLE CHILD AT PASS OVER. AND I DON'T HAVE EXPERTISE IN CHILDHOOD CANCER PARTICULARLY I DEALT WITH SOME FOLKS THAT HAVE OR HAVE BEEN FIGHTING IT. IT WAS ALWAYS MY SIMPLE UNDERSTANDING THAT THE REASON WE HAD THE KIND OF IMPROVEMENTS IN PEDIATRIC CANCER THAT WE CAN TALK ABOUT IN TERMS OF LEUKEMIA AND SMOTHERS, WERE BECAUSE ALL CHILDREN WERE ON CLINICAL TRIALS AND TO DO THAT, I PRESUMED, AND AGAIN I'M ASKING YOU TO CHECK MY ASSUMPTIONS, I PRESUME WE HAD TO HAVE SIGNIFICANT GOVERNMENT INVOLVEMENT SO THAT THAT COULD BEING AND CAREFULLY DONE. SEEMS TO ME, I MEAN I WONDER, WHETHER THAT IS NOT PARTLY THE ORIGIN OF THE FACT THAT PEDIATRIC CANCER SO DISPROPORTIONATELY OR LARGELY OR WHATEVER YOU WANT TO CALL IT, DEPENDENT ON FEDERAL FUNDING. I WONDER, YOU DIDN'T SEEM TO INDICATE THAT YOU THOUGHT IT WOULD BE VALUABLE FOR ADVOCATES TRY TO HELP CHANGE THAT BALANCE, BUT I WONDER IF YOU THINK THERE WOULDN'T BE VALUE IN HAVING MORE INDUSTRY INTEREST IN? >> SURE, AND NANCY CAN TALK ABOUT THAT. SO, ABSOLUTELY. THE NCI WAS A FUNDING SOURCE THAT LED TO CURE. I MEAN, THAT'S A FACT AND IT IS THE NCI FUNDING THAT DROVE THOSE CURES. BUT, IT'S PROBABLY MORE COMPLICATED THAN JUST ENROLLING ON CLINICAL TRIAL. WHAT HAPPENED THROUGH THE CHILDREN OF ONCOLOGY GROUP AND THE PREDECESSOR ORGANIZATIONS IS THAT PEOPLE MUCH WISER THAN ME, MANY YEARS AGO, RECOGNIZING TO WORK TOGETHER. SO THE ORIGINS OF THE COOPERATIVE GROUP DATE BACK TO THE 1950s. AND THE SUBSPECIALTY OF PEDIATRIC ONCOLOGY THAT EMERGED GREW UP AROUND CLINICAL RESEARCH, AND ENROLLING CHILDREN ON CLINICAL TRIALS IS REALLY A MESH IN OUR SUBSPECIALTY. MANY OF THE ADVANCES CAME THROUGH CLINICAL RESEARCH BUT SOME OF THE ADVANCES CAME FROM STANDARDIZATION ACROSS THE COUNTRY. BECAUSE IF ALL CHILDREN ARE BEING ENROLLED IN THE SAME PROTOCOL, THEY ARE ALL BEING TREATED THE SAME WAY. IT'S STANDARDIZATION. BUT THEN YOUR LATTER QUESTION, THE ECONOMIC MODELS FOR INDUSTRY WITHOUT GOVERNMENT INCENTIVES DON'T WORK. OUR MOST COMMON CHILDHOOD CANCER, ALL, WHICH IS MANY CANCERS, 2500 CASES A YEAR, MOST COMMON SOLID TUMOR OUTSIDE OF BRAIN TUMORS, NEUROBLASTOMA. 600 CASES A YEAR. THE ONE EXAMPLE WE HAVE WAS ALMOST AN ENTIRE DERISKING OF THE IN. CI DOING THE DEVELOPMENT AND THEN AN INDUSTRY PARTNER THAT WAS FOCUSED ON RARE DISEASES WILLING TO MAKE THE LAST STEP OF THE INVESTMENT IN A VERY PROFESSIONAL WAY. BUT THE ECONOMIC MODELS, HISTORICALLY, FOR WHAT ARE ULTRARARE DISEASES, BECAUSE MOST OF OUR OTHER DISEASES ARE LESS THAN 1000 NEW CASES A YEAR, THEY DON'T WORK. AND IT IS HARD TO ENVISION THOSE MODELS EVER WORKING WITHOUT OTHER INVENTIVES BEING PUT IN PLACE. >> DR. ADAMSON, ONE OF MY BOARD MEMBERS WHO IS WATCHING ASKED ME TO THANK YOU FOR SAYING WHAT IS ON THE MINDS OF SO MANY PEOPLE IN THE ROOM NOW WITH REGARD TO THE NEED FOR FEDERAL FUNDING FOR KIDS WITH CANCER. SO THANK YOU VERY MUCH FOR THAT. I AM FAIRLY NEW THIS WHOLE COMMUNITY, THIS WHOLE DEBATE. WHAT I ALWAYS FOUND STRIKING IS THE DICHOTOMY BETWEEN THE FACT THAT CHILDHOOD CANCER IS SO DEPENDENT ON FEDERAL FUNDING YET THE NCI BUDGET IS ROUGHLY 2-4% FOR CHILDHOOD CANCER VERSUS ALL THE OTHER CANCERS. I WAS WONDERING -- I HAVE TWO THINGS I WANT TO ASK YOU ABOUT. ONE IS, CAN YOU SPEAK TO THAT DICHOTOMY? WHY DOES BREAST CANCER AND ALL THE ADULT CANCERS GET SO MUCH MORE ATTENTION WHEN CHILDHOOD CANCERS WHICH ARE SO COMPELLING. AND SECOND, I WAS A LITTLE TAKEN ABACK BY YOUR COMMENT ON THE UNINTENDED CONSEQUENCES FOLLOWED ALMOST IMMEDIATELY SAYING THAT EMA TRUMPS -- IF YOU COULD EXPAND ON THAT A LITTLE BIT AND GIVE US MORE DIRECTION AS ADVOCATES, WHAT WE OUGHT TO BE DOING VIS-A-VIS THE EMA. >> THANK YOU. SO, IN REVERSE ORDER, THE EMA REGULATIONS HAVE HAD POSITIVE CONSEQUENCES. I DON'T WANT PEOPLE TO WALK AWAY THINKING IT'S ALL UNINTENDED CONSEQUENCES. UNINTENDED CONSEQUENCES IS THAT IT IS A REQUIREMENT. AND DRUGS DON'T GET JUST STUDIED IN THE U.S., THEY GET STUDIED GLOBALLY. SO A DRUG COMPANY HAS A REQUIREMENT IT MUST FULFILL IN THE FORM OF A PIP. THEY ARE REQUIRED TO DO THAT. ON THE U.S. SIDE, WE HAVE A SYSTEM THAT ACTUALLY WORKS EXTREMELY WELL AND THAT WAS INCENTIVE THAT MANY COMPANIES TOOK AN ADVANTAGE OF. BUT THE FDA SAYS IT'S NOT A REQUIREMENT FOR THEM. SO REQUIREMENTS TRUMP VOLUNTARY PROCESSES. NOW, THE OTHER QUESTION, THE BUDGET. AGAIN, SCIENCE SHOULD DRIVE IT. AND THE BURDEN OF CANCER IS SIGNIFICANT AND WE DO NOT WANT TO PIT A SPECIFIC DISEASE OR ONE SPECIFIC DISEASE AGAINST ANOTHER. I'M SURE THERE IS NO ONE IN THE NCI WHO SAYS WE SHOULD NEGLECT PEDIATRIC CANCER. BUT IN PART, IT MAY BE THE CART BEFORE THE HORSE. HOW DO YOU GET MORE PEOPLE TO BECOME SCIENTISTS LIKE JOHN? WELL, YOU PUT THE RFAs OUT THERE. PEOPLE WILL FOLLOW THE MONEY. WHERE IS THE MONEY? DO WE HAVE SPECIFIC RFAs? AND I AGREE WITH LEE. WE DON'T WANT A LESSER QUALITY SCIENCE FOR PEDIATRIC CANCER. BUT, UNLESS YOU PRIME THE PUMP, WE ARE PROBABLY ALWAYS GOING TO BE STUCK HERE. AND I THINK THERE ARE PEOPLE SMARTER THAN ME IN THIS ROOM AND OTHER AREAS, HOW CAN WE PRIME THE PUMP? AND I THINK THAT IS THE WAY TO DO IT. NOT TO NECESSARILY FOCUS ON -- BECAUSE MATH CAN GET FUZZY. BUT IT'S A SMALL PERCENTAGE. I DON'T THINK ANYONE KNOWS WHAT THE RIGHT NUMBER IS, BUT I DO THINK THAT EVERYONE WOULD AGREE, WE NEED TO ATTRACT MORE SCIENTISTS TO THE PROBLEM. WE REFER TO PEDIATRIC CANCER AS A CANCER TO MORE THAN 100 DIFFERENT TYPES OF CANCER. SO, AND I THINK LASTLY, WHY HAVE OTHERS BEEN MORE SUCCESSFUL? PARTLY A NUMBERS ISSUE. THERE ARE FAR MORE ADULTS INFLICTED WITH CANCER. BUT IT IS ONLY, I THINK, AND MORE RECENT YEARS, THE PEDIATRIC ADVOCACY COMMUNITY IS GAINING MORE EXPERIENCE. AND DON'T FORGET, THE PATIENTS AND FAMILIES THAT ARE AFFECTED BY CHILDHOOD CANCER ARE YOUNG FAMILIES. THEY ARE YOUNG FAMILIES STARTING OUT IN LIFE. AND ALL THE HURDLES YOU FACE AS A YOUNG FAMILY, THEY HAVEN'T ESTABLISHED THEMSELVES ECONOMICALLY AND HAVEN'T RISEN TO HIGH LEVELS IN CORPORATIONS. IT'S A PEAK AGE, TWO-6 YEARS. SO, IT IS VERY DIFFICULT FOR FAMILIES WITH CHILDREN WITH CANCER TO ALSO BECOME ADVOCATES. IT'S WACKERRABLE WE HAVE THE NUMBER OF ADVOCATES WE DO. -- IT'S REMARKABLE. PART OF IT IS FAMILIES WHO ARE AFFLICTED WITH CHILDHOOD CANCER AND THEIR ABILITY TO CHANGE THE DIALOGUE. I'M AMAZED AT THE SUCCESS THAT ADVOCACY GROUPS HAVE HAD BUT RECOGNIZE THEY ARE THE OUTLIERS RIGHT NOW AND THAT'S UNDERSTANDABLE GIVEN THE INCREDIBLE BURDEN THAT CHILDHOOD CANCER PLACES ON THEM. SOME OF THEM I'LL GO OVER QUICKLY BECAUSE WE HIT ON A NUMBER OF THESE. BUT I JUST WANTED TO POINT OUT THAT I'M VERY WELL AWARE OF THIS CHALLENGE. AND I SEE IT NOW FROM A VERY DIFFERENT PERSPECTIVE, HAVING PREVIOUSLY CHAIRED THE CHILDREN'S ONCOLOGY GROUP AND HAVING SPENT 35 YEARS AS A PRACTICING PEDIATRIC ONCOLOGIST AND CLINICAL INVESTIGATOR, AND NOW WEARING THE UGLY REGULATOR HAT. I'M AWARE OF SOME OF THE ISSUE THAT IS WE ARE TRYING TO DISCUSS TODAY. I WANT TO EMPHASIZE DESPITE THE DIFFERENCES BETWEEN PEDIATRIC AND ADULT CANCERS THAT WE KNOW ABOUT ALL TOO WELL, DRUG DISCOVERY AND DEVELOPMENT FOR PEDIATRIC CANCER REALLY HIGHLY LEVERAGES THAT FOR COMMON ADULT CANCERS. I THINK THAT MAY CHANGE TO SOME EXTENT IN THE YEARS AHEAD. BUT RIGHT NOW, THAT IS SORT OF THE REALITY. AND I THINK THERE ARE OPPORTUNITIES AND OPPORTUNITIES TO UTILIZE EXISTING LEGISLATION TO MAKE THAT LEVERAGING A LITTLE BIT MORE A REALITY. JUST WANTED TO GO OVER SOME CONSENSUS COMMENTS FROM THE PEDIATRIC SUBCOMMITTEE OF THE ONCOLOGIC DRUGS ADVISORY COMMITTEE. AND THESE ARE FROM 5 OR 6 YEARS AGO WHEN I ACTUALLY CHAIRED THAT GROUP. AND I THINK THEY DO STILL REFLECT THE POSITION OF THE FDA, THAT DRUG DEVELOPMENT FOR PEDIATRIC CANCERS SHOULD BE COORDINATED AS PART OF OVERALL ONCOLOGY DRUG DEVELOPMENT PLANS. THE EVIDENCE BURDEN FOR INITIATING CLINICAL STUDIES IN CHILDREN WITH CANCER SHOULD OBVIOUSLY INCLUDE BIOLOGICAL JUSTIFICATION AND SOME EXPECTATION OF POTENTIAL BENEFIT. REASONABLE EXPECTATION OF SAFETY, AND INFORMATION TO GUIDE APPROPRIATE DOSING. AND I THINK CASE-BY-CASE DETERMINATIONS OF WHEN THESE STUDIES COULD BE INITIATED IN CHILDREN ARE REALLY MADE ON THE BASIS OF THE TYPE OF AGENT, MECHANISM OF ACTION, WHAT IS KNOWN ABOUT THE POTENTIAL OR SAFETY PROFILE AND POTENTIAL INDICATION. AND I THINK THE MOST STRIKING IS THAT THE CURRENT PRACTICE THAT PEDIATRIC STUDIES COULD BE INITIATED IMMEDIATELY FOLLOWING ADULT PHASE 1 STUDIES, REMAINS. UNFORTUNATELY, IT IS SOMETIMES DIFFICULT TO CONVINCE THE INDUSTRY SPONSORS OF THAT. BUT I THINK EACH MORE IMPORTANT THAN FOLLOWING PHASE I STUDIES, THERE IS NO OBJECTION ON THE PART OF THE AGENCIES THAT FIRST IN HUMAN STUDIES COULD, IN SOME APPROPRIATE SITUATIONS, AND SPECIFIC DISEASES, AND WITH SPECIFIC AGENTS, BE FIRST IN CHILDREN STUDIES. AND THAT IS SOMETHING CLEARLY WE ALL WANT TO SEE. IN A REPORT TO CONGRESS YEARS AGO, THE FDA COMMITTED TO THE DEVELOPMENT OF INEFFECTIVE AND SAFE THERAPIES FOR CHILDHOOD MALIGNANCIES AND IT BELIEVED, AND I THINK IT STILL DOES, THAT ITS INITIATIVES COULD ASSIST IN PEDIATRIC NEW DEVELOPMENT GENERALLY AND IN PEDIATRIC CANCER THERAPY DEVELOPMENT SPECIFICALLY. AND AGAIN, I THINK THERE ARE OPPORTUNITIES TO MAKE THESE INITIATIVES WORK A LITTLE BIT BETTER. AS DR. ADAMSON POINTED OUT, THE LEGISLATIVE INITIATIVES ARE NOT PERFECT. THEY WERE WELL INTENTIONED. THEY ARE INTERPRETED PRIMARILY BY MEDICAL ONCOLOGY REVIEWERS WITHIN THE FDA AND SOMETIMES THERE IS REALLY LIMITED HUMAN EXPERIENCE, PERSONAL EXPERIENCE WITH PEDIATRIC CANCER AND THERE IS AN OVER EMPHASIS ON SAFETY AND TOXICITY CONCERNS AND I THINK THAT CAN AND WILL CHANGE. PEDIATRIC PATIENTS SHOULD BE GIVEN MEDICINE THAT HAVE BEEN EVALUATED AND PRODUCT DEVELOPMENT SHOULD ALWAYS INCLUDE PEDIATRIC STUDIES WHEN USE IS ANTICIPATED. AND THE REASON FOR THIS REALLY DATES BACK MANY YEARS AND WITH THE BEGINNING OF THE FOOD, DRUG AND COSMETIC ACT WHEN UNTESTED AND UNLABELED DRUGS WERE USED AND RESULTED IN HORRIFIC TOXICITIES AND 90% OF THOSE WERE IN CHILDREN UNDER SIX YEARS OF AGE. SO, THERE IS A BIT OF OVERSENSITIVITY ON THE PART OF ASSURING SAFE USE. DESPITE THAT, UP UNTIL 1994, THERE WASN'T EVEN A REQUIREMENT FOR PEDIATRIC USE LABELING OF NEW PRODUCTS. AND THE FACT THAT THERE WAS NO REQUIREMENT CERTAINLY MEANT THERE WERE VERY FEW STUDIES OF NEW DRUGS IN THE PEDIATRIC POPULATIONS. AND THIS WAS ALTERED BY THE FOOD DRUG ADMINISTRATION MODERNIZATION ACT IN 97. WHICH INTRODUCES THE CONCEPT OF PEDIATRIC EXCLUSIVITY AND PHARMACEUTICAL SPONSORS COULD GET SIX MONTHS OF PATENT EXTENSION ON A NEW MOLECULAR ENTITY IF THEY DID PEDIATRIC STUDIES AS OUTLYING A WRITTEN REQUEST FROM THE AGENCY. THIS WAS EXTENDED IN PRINCIPLE TO THE PEDIATRIC RULE THAT THIS HAD TO BE DONE. IT WAS INCENTIVE AND IN A VOLUNTEER AREA INCENTIVE PROGRAM. THE RULE WAS OVERTURNED BUT REPLACED A FEW YEARS LATER WITH THE PEDIATRIC RESEARCH EQUITY ACT, WHICH REPLACED THE PEDIATRIC RULE. AS DR. ADAMSON ALSO MENTIONED, THESE HAVE HAD REALLY PROFOUND IMPACT ON THE USE OF DRUGS IN CHILDREN WITH NOW MORE THAN 500 PRODUCTS WITH LABELING THAT RESULTED FROM STUDIES IN THE PEDIATRIC POPULATION. UNFORTUNATELY, THE AREA THAT IS LEAST REPRESENTATIVE OF ALL THE CLINICAL AREAS IS ONCOLOGY. AND THAT MANY OF THE DRUGS THAT HAVE BEEN EVALUATED HAVEN'T DEMONSTRATED EFFICACY, SO, ETHICAL INFORMATION IS NOT INCLUDED ON LABELS OF THESE AGENTS. ALL OF THESE OR BOTH OF THESE IMPORTANT PIECES OF LEGISLATION WERE SET TO SUNSET. AND YOU CAN SEE THEY WERE REVIEWED OR RENEWED EVERY FIVE YEARS WHICH WAS ENORMOUS TASK TO KEEP REAUTHORIZING THESE. BOTH OF THESE WERE PERMANENTLY REAUTHORIZED LAST YEAR AS PART OF THE FOOD DRUG ADMINISTRATION SAFETY AND INNOVATION ACT. THE EUROPEAN UNION HAS AN ORGANIZATION, THE EUROPEAN MEDICINES AGENCY, EMA, WHICH IS THE SORT OF COUNTERPART FROM A REGULATORY PERSPECTIVE, FOR MARKETING AUTHORIZATION OF PRODUCTS IN THE EU. AND THERE ARE PEDIATRIC REGULATIONS WERE DELAYED. THEY WERE SO IMPRESSED BY WHAT THE EXCLUSIVITY PROVISION COULD DO THAT THEY ALSO WENT A STEP FORWARD AND NOT ONLY MADE THIS VOLUNTARY, BUT ACTUALLY MANDATED PEDIATRIC DEVELOPMENT PLANS. THE PROBLEM IS THAT AGAIN, THESE PEDIATRIC DEVELOPMENT PLANS ARE VERY MUCH THE SAME AS IN THE U.S. AND THAT THEY ARE INDICATION DRIVEN. SO ACTUALLY GRANTING WAIVERS HAS BEEN THE REASON FOR MANY OF THE DELAYS. AND I THINK THERE REALLY ARE OPPORTUNITIES WHEN THE EMA IS SITTING ON A PLAN THAT IS ACTUALLY BEEN WHERE THERE IS A REQUEST FOR A WAIVER OR DEFERRAL OR DELAY THAT WE COULD ACTUALLY MAKE SOME HEADWAY IN THIS COUNTRY MOVING FORWARD WITH THE STUDIES. AS WE GO THROUGH A LITTLE BIT OF ACRONYMS HERE, BPCA, BEST PHARMACEUTICALS FOR CHILDREN ACT, FDASIA AND THE PEDIATRIC ODAC, A SUBCOMMITTEE OF THE ONCOLOGIC DRUGS ADVISORY COMMITTEE WHICH DOESN'T VOTE AND MAKE RECOMMENDATIONS AS FAR AS APPROVAL BUT WE TRIED TO REORGANIZE IT SO THAT WE CAN FOSTER COMMUNICATION COLLABORATION BETWEEN CLINICAL INVESTIGATORS, ADVOCATES AND INDUSTRY. AND THEN THE PROCESS BY WHICH SPONSORS CAN SUBMIT PROPOSALS, THE PROPOSED PEDIATRIC STUDY REQUESTS WHICH COULD RUM IN THE AGENCY ISSUING A WRITTEN REQUEST, WHICH IF THE CONDITIONS OF THAT REQUEST COMPLETED STUDIES ARE MET, RESULTS IN THE PEDIATRIC EXCLUSIVITY. WHICH I MIGHT SAY IS REALLY QUITE SIGNIFICANT FROM A FINANCIAL PERSPECTIVE, AT LEAST HAS BEEN HISTORICALLY. AND WITH THE ASTRONOMICAL COSTS OF CURRENT DRUGS THAT ARE BEING DEVELOPED AND THE EXPENSE OF THOSE PROGRAMS, THE FINANCIAL OPPORTUNITIES THAT DO COME BACK TO INDUSTRY ARE ENORMOUS OR COULD BE ENORMOUS. SO I THINK SOME OF THE COMMENTS WERE MADE EARLIER ABOUT UTILIZING THAT LEVERAGE TO INCREASE SUPPORT FROM THE PHARMACEUTICAL INDUSTRY IS REALLY WELL JUSTIFIED. SO THESE LAWS DO WORK TOGETHER AND THE STUDIES ARE MANDATORY. THE CATCH HERE IS THAT THE REQUIRED STUDIES ARE FOR THE ADULT INDICATION UNDER REVIEW. SO CHILDREN DON'T GET THE COMMON CANCERS OF ADULTS AND THIS ISN'T EXCLUSIVE TO ONCOLOGY. BECAUSE OTHER PRODUCTS DEVELOPED FOR SPECIFIC ADULT INDICATIONS ALSO ANTIADEQUATELY STUDIED IN CHILDREN. A CASE-IN-POINT IS THE WIDE UTILIZATION OF ANTI-THROMBOTIC AGENTS WHICH EFFECT THE CHILDREN WITH CANCER SIGNIFICANTLY, WHICH HAVE NEVER REALLY BEEN ADEQUATELY STUDIED IN PEDIATRIC AGE GROUP UNTIL VERY RECENTLY WE MADE SOME HEADWAY. BECAUSE SPONSORS COME IN WITH INDICATIONS THEY ONLY WILL BE USED IN ADULTS FOLLOWING HIP REPLACEMENT SURGERY. SO STAINS INDICATION DOESN'T EXIST, THEY ARE EXEMPT FROM DOING PEDIATRIC STUDIES BUT THAT IS CHANGING. THE OTHER WAY THIS IS WAIVED IS IF A PRODUCT IS DEVELOPED FOR OVER AN INDICATION, A DISEASE -- ORPHAN INDICATION, A DISEASE THAT EFFECTS LESS THAN 2000 INDIVIDUALS A YEAR, AND IT NOW APPLIES TO DRUGS AS WELL AS TO BIOLOGICS. IN THE PAST, BIOLOGIC AGENTS WERE ALSO EXEMPT. BPCA, THE STUDIES ARE VOLUNTARY FOR THE ENTIRE ACTIVE MIGHTY. THEY MAY BE ISSUED FOR ORPHAN INDICATIONS. SO WHEN YOU HAVE AN ORPHAN PRODUCT YOU ALREADY GET SEVEN YEARS OF PATENT EXCLUSIVITY AND THIS WOULD BE A WAY OF GETTING ADDITIONAL PATENT EXTENSION ON AN ORPHAN DRUG AND APPLIES TO BIOLOGICS AS WELL AS DRUGS. SO I THINK SOME OF THE CHALLENGES, AS NOW I HAVE SEEN ON THE DRUG APPROVAL PROCESS FROM THE FDA PERSPECTIVE IS THAT CLINICAL TRIALS, WHICH LEAD TO DRUG APPROVAL UNTIL ADULTS AND CHILDREN ARE VERY, VERY DIFFERENT. WE HAVE DIFFERENT CLINICAL OBJECTIVES IN THE INITIAL MANAGEMENT APPROACH TO CHILDREN WITH CANCER AS COMPARED TO ADULTS, MANY WHOM PRESENT WITH METASTATIC DISEASE. SO PROLONGING SURVIVAL FOR INDETERMINANT PERIODS OF TIME OR PROGRESSION-FREE SURVIVAL FOR 2-4 MONTHS, IS NOT REALLY TERRIBLY GERMANE TO THE PEDIATRIC ONCOLOGY COMMUNITY. WE ARE MORE INTERESTED IN CURE AND QUALITY OF SURVIVORSHIP. MANY BLOCKBUSTER ADULT ONCOLOGY DRUGS ARE APPROVED FOR SECOND AND THIRD LINE TREATMENT INDICATIONS. WE DON'T EVEN WANT TO HAVE THE SECOND AND THIRD LINE NECESSITY. SO THESE INDICATIONS ARE MUCH LESS RELEVANT IN CHILDREN. AND PREAGGRESSION-FREE SURVIVAL AS AN ENDPOINT, IF WE CAN PROVE THERE IS A CLINICAL BENEFIT ASSOCIATED WITH THAT IT IS IMPORTANT. AND AS A PREVIOUS FDA COMMISSIONER AND NCI DIRECTOR, THOUGHT THIS WAS THE WAVE OF THE FUTURE HAS NEVER BEEN A PEDIATRIC PERSPECTIVE. SO SO WE HAVE PROBLEMS. RARE DISEASES AND THE REQUIREMENT FOR MULTI-CENTER TRIALS BUT THE FACT THAT WE HAVE THE CLINICAL TRIAL INFRASTRUCTURE WE HAVE IS AN EXTRAORDINARY OPPORTUNITY. AS HAS BEEN MENTIONED, THE SEGMENTATION OF TUMOR DIAGNOSIS BY GENOMIC CLASSIFICATION IS FURTHERED GOING TO DIMINISH SAMPLE SIZE AND I THINK WE ARE ALREADY SEEING SOME PROBLEMS WITH PRECISION THERAPY APPROACHES. BUT I THINK THIS IS GOING TO BE A PROBLEM THAT NOT ONLY WE IN PEDIATRIC ONCOLOGY FACE BUT I THINK IT IS GOING TO BE I A DRUG APPROVAL CHALLENGE IF YOU WILL, WITHOUT BASKET PROTOCOLS OR MASTER PROTOCOLS. SO, I THINK AGAIN, THERE IS AN OPPORTUNITY TO TAKE ADVANTAGE OF THIS SITUATION. RARELY, IF EVER, OUR COOPERATIVE GROUP AND CLINICAL TRIALS, WHICH ARE ALWAYS MULTI-AGENT AND MULTIMODALITY OR GENERALLY SPEAKING, PLANNED AS REGISTRATION TRIALS. THAT IS DRUG APPROVAL TRIALS OR APPROVAL FOR MARKETING AND WITH THE APPROPRIATE LABELING. CLINICAL TRIAL OBJECTIVES HAVE BEEN TO IMPROVE EVENT-FREE SURVIVAL AND REDUCE TOXICITIES AND THEY HAVEN'T BEEN DESIGNED TO ACHIEVE LICENSING APPROVAL OR MARKETING AUTHORIZATION. EVEN WHEN WE TRIED TO DO IT WITHIN THE CONTEXT OF WHAT OUR PRIMARY OBJECTIVES IN COG TRIALS HAVE BEEN, IT'S BEEN A REAL CHALLENGE. ONE DRUG THAT RECEIVED ACCELERATED APPROVAL FOR PEDIATRIC CANCER SOME 12 OR 13 YEARS AGO NOW, THAT REQUIRES A CONFIRMATORY STUDY. IT WAS TO BE DONE BY COG AND 13 YEARS LATER IS STILL NOT BEING DONE FOR REASONS THAT ARE RELATED TO THE FACT THAT THESE ARE MULTI-AGENT TRIALS AND TRIED TO DESIGN THE TRIALS SO WE COULD ISOLATE THE EFFECT OF THIS NEW DRUG. AND IT IS PROVEN QUITE DIFFICULT. THE ONLY SINGLE-AGENT THERAPIES ARE EARLY DOSE FINDING AND EARLY EFFICACY STUDIES. SO, WHEN WE LOOK AT OUR APPROACH WITH COMBINATION THERAPIES GENERALLY, DRUG APPROVALS REQUIRE DEFINITIVE EFFICACY ASSESSMENT AND ISOLATION OF THE EFFECT OF THE DRUG IN QUESTION, AND I THINK OUR COMBINATION THERAPY APPROACH, ALTHOUGH CHALLENGING, CAN BE ADDRESSED AND I THINK THERE WILL BE ADDITIONAL COMPLEXITIES WITH TARGETED AGENTS AND USING TARGETED AGENTS IN COMBINATION AND TARGETED AGENTS IN COMBINATION WITH CONVENTIONAL THERAPY. SO, HOW BEST TO DESIGN NEW STUDIES BECAUSE THERE IS ALWAYS A VERY CONSERVATIVE APPROACH TO PREVENT EROSION OF CURRENT RESULTS IN THE RISK AVERSION THAT WE KNOW TOO WELL. BUT IT'S NOT A VERY EFFICIENT WAY TO GET DRUGS EVALUATED AND APPROVED. BUT ALWAYS, THERE IS THE REQUIREMENT TO ISOLATE THE EFFECT OF A NEW DRUG. I THINK WE HAVE BEEN THROUGH SOME OF THIS AND THE INDICATION-BASED PRA TRIGGERS ARE REALLY NOT RELEVANT FOR CHILDHOOD CANCER. BUT NOW THERE ARE SOME OPPORTUNITIES FOR US TO USE THIS TO OUR ADVANTAGE WHILE WE ALSO LEVERAGED THE WRITTEN REQUEST OPPORTUNITIES. THERE ARE CERTAINLY OTHER INCENTIVE MODELS. NANCY WILL SPEND TIME AND I'LL MENTION IT A BIT. BUT MAYBE SIX MONTHS PATENT EXCLUSIVITY ISN'T LONG ENOUGH. COULD IT BE 12 MONTHS OR TWO YEARS? COULD IT BE RELATED TO THE ULTIMATE PROFITABILITY OF A PARTICULAR AGENT IN QUESTION? SO JUST HAVING THE FLAT SIX MONTH APPROACH IS THAT SOMETHING THAT SHOULD BE EVALUATED? AGAIN, THE BASIS FOR A NEW DRUG APPROVAL WE WERE MANDATED BY LAW TO ABIDE BY IS DEMONSTRATING EFFICACY WITH ACCEPTABLE SAFETY AND ADEQUATE WELL CONTROLLED STUDIES. AND YOU SEE THAT STUDIES IS PLURAL. THERE IS ALREADY SIGNIFICANT FLEXIBILITY ON THE PART OF THE AGENCY AND MANY ONCOLOGY DRUGS ARE APPROVED FOLLOWING A SINGLE STUDY AND OBVIOUSLY IN PEDIATRIC ONCOLOGY. THAT IS IMPORTANT. WHAT WE REALLY STRIVE FOR IS THE ABILITY TO GENERATE PRODUCT LABELING THE FINES IN APPROPRIATE POPULATION FOR TREATMENT WITH THE DRUG. THIS IS WHAT DRIVES THE ENTIRE MODE US OP RUN DIOF THE FDA IS LABELING, LABELING, LABELING. AS A PRACTICING PHYSICIAN FOR TOO MANY YEARS THEY WANT TO ADMIT, I CAN COUNT ON ONE HAND THE NUMBER OF TIMES THEY ACTUALLY READ FULLY A PRODUCT LABELING. NONETHELESS, THAT'S WHAT WE ARE OBLIGATED BY LAW TO ASSURE THAT THE LABELING PROVIDES ADEQUATE INFORMATION FOR SAFE AND EFFECTIVE USE IN PRESCRIBING OF THE DRUG. SO THERE ARE DIFFERENT APPROVAL PATHWAYS, REGULAR APPROVAL W CLINICAL BENEFIT IS OR USING AN ESTABLISHED SURROGATE FOR LIFE-THREATENING CONDITIONS, PARTICULARLY CANCER, THE AGENCY STRIVES PROVIDE ACCESS WHILE DEFINITIVE EFFICACY IS BEING COLLECTED. AND THAT LED TO THE ACCELERATED APPROVAL PATHWAY WHICH PROVIDES AN OPPORTUNITY TO USE A SURROGATE ENDPOINT THAT STUDIES COULD BE SHORTER IN DURATION. THESE SURROGATES WERE EXPECTED TO LIKELY PREDICT CLINICAL BENEFIT GENERALLY OVER ALL SURVIVAL WHICH IS THE AGENCIES GOLD STANDARD. I THINK THERE ARE OPPORTUNITIES FOR FLEXIBILITY IN REGULATORY DECISION-MAKING WITH RESPECT TO PEDIATRIC DRUG APPROVALS. EARLY COMMUNICATION AND THOUGHTFUL COLLABORATIVE PLANNING ARE KEY TO AFFECTING CHANGE WHETHER IT IS -- AND I THINK ALL STAKEHOLDERS SHOULD BE PART OF THE DISCUSSIONS UINVESTIGATORS, REGULATORS ON BOTH SIDES OF THE OCEAN AND ADVOCATES. AND OBVIOUSLY INVESTIGATORS. THERE ARE, I BELIEVING, ALTERNATIVE ENDPOINTS THAT COULD BE USED TO DEFINE CLINICAL BENEFIT. AND WE HAVE APPROVED DRUGS FOR CHILDHOOD CANCER LOOKING JUST AT PHARMACOKINETICS. BUT, ARE THERE OTHER NOVEL ENDPOINTS SINCE STEM CELL TRANSPLANT IS A BIG PART OF COMBINATION INTENSIVE THERAPY APPROACHES? COULD YOU LOOK AT THE DURATION OF EVENT-FREE SURVIVAL PRIOR TO MOVING ON TO TRANSPLANT IN SOME LEUKEMIA RETRIEVAL STUDIES? AND THE USE OF ASSESSMENT OF FUNCTIONALITY AND SYMPTOM IMPROVEMENT, WHICH IS NOW BEING USED TO A SIGNIFICANT EXTENT IN PEDIATRIC OR IN ADULT CANCER DRUG DEVELOPMENT T IS SOMETHING THAT REALLY REQUIRES SOME INTENSE INVESTIGATION OR INVESTMENT IN THE FUTURE. HIS STORE CALL CONTROLS VEHICLE A PLACE. WE ALL LABORED UNDER THE DILUTION THAT THE AGENCY WON'T LOOK AT APPLICATIONS THAT DEPEND ON HISTORICAL CONTROLS. WE WILL. THEY HAVE TO BE CONSTRUCTED IN SUCH A WAY THAT THERE IS RELATIVE ASSURANCE WHAT IS BEING PRESENTEDDED AS HISTORICAL IS IN FACT TRUE AND VERIFIABLE. AND I THINK THERE IS ALSO THE CONCERN ABOUT EROSION OF CURRENT EXCELLENT OUTCOME RESULTS IN MANY PEDIATRIC CANCERS, MOST PEDIATRIC CANCERS THAT MAKE SOME REGULATORS A LITTLE BIT NERVOUS. SO RATHER THAN REQUIRING COMPARATIVE EFFICACY STUDIES OR NONINFERIORITY STUDIES OR SUPERIORITY STUD CHEESE TAKE A LONGER TIME LOOKING AT LONG TERM SAFETY STUDIES, IT MIGHT BE ANOTHER WAY TO DO THIS. WE ARE ABLE TO ACCOMPLISH SOME FLAX BELTY. I THINK SOME OF THE NEW REQUIREMENTS FOR PEDIATRIC STUDY PLANS THAT HAVE BEEN REQUIRED NOW BYE, DOES ALLOW EXTENSION BUT MORE IMPORTANTLY, I THINK IT CAN RESULT IN THE TIMING OF OUR CONSIDERATION OF WRITTEN REQUESTS. THE DEVELOPMENT TIME LINES IN EUROPE AS DR. ADAMSON MENTIONED, THEY DEVELOPED THEIR PIP EARLY AND THEN THERE CAN BE MANY MODIFICATIONS BEFORE IT IS SIGNED OFF ON. FREQUENTLY IT'S A WAIVER AND GOES NOWHERE. SO, BEFORE ANY PEDIATRIC STUDIES ARE DONE, A PIP HAS TO BE FINALIZED. IN THE U.S., THERE IS NO REQUIREMENT FOR ANY DECISION REGARDING PHASE I AND PHASE II STUDIES. SO WE REALLY NEED TO MAKE SURE THAT SPONSORS ARE AWARE THAT THERE IS NO OBSTRUCTION TO EARLY INVESTIGATIONS OF NEW AGENTS IN CHILDREN. THERE IS NOW REQUIREMENT THAT IF THE SAME CONDITION EXISTS, THAT A PEDIATRIC STUDY PLAN HAS TO BE PRESENTED FOR EVALUATION AND APPROVAL FOLLOWING MODIFICATIONS BEFORE A NEW DRUG WILL BE APPROVED. BUT AGAIN, THIS IS ONLY IF THE SAME INDICATION EXISTS. BUT I THINK WHEN WE SEE THESE AND KNOW THAT THESE MAY BE AGENTS IN WHICH THERE IS A POTENTIAL RELEVANCE IN THE PEDIATRIC CANCER POPULATION, THEN WE CAN WORK WITH SPONSORS AND INVESTIGATORS TO DISCUSS POSSIBLE WAYS TO ACCELERATE AND EXPEDITE STUDIES IN CHILDREN. THIS IS JUST THE REQUIREMENTS OF AN INITIAL PEDIATRIC STUDY PLAN, AND THEY CAN IN FACT BE USED, EVEN THOUGH THEY FREQUENTLY REQUIRE MODIFICATION BACK AND FORTH. THEY CAN IN FACT BE USED TO STIMULATE THE DEVELOPMENT OF A WRITTEN REQUEST, WHICH COULD RESULT IN THE PATENT EXCLUSIVITY OR THE PEDIATRIC EXCLUSIVITY FOR A NEW AGENT. SO PRIORITY REVIEW VOUCHER INITIATIVE, THE RARE DISEASE PRIORITY REVIEW VOUCHER WAS ALSO PART OF FIDUCA, TITLE 9, SECTION 908, WHICH AMENDED THE FOOD, DRUG AND COSMETIC ACT BY ADDING A SECTION 529. WHICH ALLOWED THE SECRETARY OF HHS TO AWARD A PRIORITY REVIEWED VOUCHER TO A SPONSOR OF A RARE PEDIATRIC DISEASE PRODUCT APPLICATION UPON APPROVAL BY THE SECRETARY OF SUCH A RARE PEDIATRIC DISEASE PRODUCT APPLICATION AND OBVIOUSLY WHAT THIS MEANS IS THAT APPROVAL OF AN APPLICATION BY THE FDA FOR A SPECIFIC PEDIATRIC INDICATION. IT ENTITLED THE HOLDER OF THE VOUCHER TO REQUEST A PRIORITY REVIEW OF ANY SINGLE HUMAN DRUG APPLICATION. SO, GENERALLY, WE WOULD NOT ANTICIPATE THIS BEING USED FOR PRIORITY REVIEW OF A PEDIATRIC PRODUCT. BUT OF A PRODUCT THAT IS GOING TO HAVE A SIGNIFICANT MARKET AND IN FACT, COULD BE SOMETHING THAT HAS A TREMENDOUS FINANCIAL VALUE. THAT COMPANY -- TO THAT COMPANY OR ANOTHER COMPANY. THE RARE PEDIATRIC DISEASE IS DEFINED AS A DISEASE THAT PRIMARILY EFFECTS INDIVIDUALS FROM BIRTH TO 18 YEARS. THIS IS A LITTLE BIT DIFFERENT THAN HOW THE FDA DEFINES CHILDREN AS UP TO AGE 16. BUT NONETHELESS, THIS IS WHAT IS IN THE STATUTE. AND EFFECTS WE INTERPRETED TO MEAN GREATER THAN 50% OF THE PREVALENCE OF THE DISEASE EXISTS IN THE POPULATION 0-18 YEARS OF AGE. THIS IS PREVALENCE AND NOT INCIDENTS. THERE ARE SOME MISCONCEPTIONS ABOUT THAT AS WELL. SO THE LAW DOES DEFINE TO SOME EXTENT, THE PROCESS FOR APPLYING. THIS HAS BEEN PUT INTO A GUIDANCE THAT IS UNDERGOING REVIEW INTERNALLY. IT CAN'T BE OR CAN'T CONTAIN ANIESTER OR SALT OF A PREVIOUSLY APPROVED AGENT SO THIS IS ONLY FOR NEW MOLECULAR ENTITIES. IT HAS TO BE A DRUG THAT HAS POTENTIAL SIGNIFICANT CLINICAL IMPACT AND ELIGIBLE FOR PRIORITY REVIEW. IT RELIES THE APPLICATION HAS TO RELY ON CLINICAL DATA, DERIVE FROM PEDIATRIC STUDIES. SO IN THE GUIDANCE WE HAVE ELABORATED THAT NOT 100% OF THE PATIENTS HAVE TO BE CHILDREN ENROLLED. SO THERE ARE SOME RARE DISEASES WHICH PRIMARILY EFFECT CHILDREN BUT SOME ADULTS MAY BE ENROLLED AS WELL AND WE DIDN'T WANT TO EXCLUDE THE POP SITUATIONS. AND THERE HAS TO BE A REQUIREMENT THAT THERE IS NO PLAN TO SEEK APPROVAL FOR ADULT INDICATION WITHIN THIS ORIGINAL DISEASE OR RARE DISEASE APPLICATION. AND THIS IS INTERPRETED TO MEAN AN INDICATION DISTINCT FROM OR ANOTHER INDICATION IN THE ADULT POPULATION FROM THAT IN CHILDREN. SO SPONSORS MAY REQUEST DESIGNATION BEFORE THEY SUBMIT AN APPLICATION FOR THIS EITHER AT THE TIME THEY REQUEST ORPHAN DESIGNATION, WHICH MOST COMPAES WILL DO BECAUSE THIS PROVIDES AN EXCLUSIVITY INCENTIVE AS WELL. AND THEY MAY REQUEST FAST TRACK DESIGNATIONS. SO AN EXPEDITED REVIEW AND APPROVAL PROCESS WITHIN THE FDA. THE DESIGNATIONS AREN'T PREREQUISITE OR RERADIO ACQUIRED FOR RECEIVING A PRIORITY REVIEW UNDER THE PROGRAM. AND JUST GETTING THE DESIGNATION DOESN'T NECESSARILY MEAN THAT THE PRODUCT IS ELIGIBLE FOR THE REVIEW. OR THAT THE APPLICATION OF THE PRODUCT IS GOING TO END UP BEING APPROVED. THE FINAL ELIGIBILITY IS REALLY BASED AT THE END OF THE REVIEW. IMPORTANT THING IS THAT THE VOUCHERS MAY BE TRANSFERRED, INCLUDING BY SALE TO OTHER COMPANIES. THERE IS NO LIMIT TO THE NUMBER OF TRANSFERS FOR ANY PARTICULAR VOUCHER. THERE IS A REQUIREMENT FOR THE FDA TO TRACK THESE TRANSFERS AND THAT IS A PROCESS THAT IS STILL BEING WORKED OUT. APPLICANTS WHO USE THEM NEED TO NOTIFY THE FDA PRIOR TO THEIR USE AND THERE ARE STILL PRESCRIPTION DRUG USER FEE APPLICATIONS THAT ARE INVOLVED. SO THERE WAS A WORKING GROUP ESTABLISHED TO ACTUALLY IMPLEMENT THE PROGRAM AND AS I MENTIONED, WE HAVE FINISHED INTERNALLY THE GUIDANCE WHICH IS NOW BEING REVIEWED. IT IS A LITTLE BIT DIFFERENT THAN MANY GUIDANCES IN THAT IT IS WRITTEN IN SORT OF A QUESTION AND ANSWER FORM AND I THINK WE WILL BE INFORMATIVE TO POTENTIAL SPONSORS. IT GOES OVER THE PROCESS FOR DESIGNATION. THE PROCESS OR REQUIREMENTS FOR VOUCHER ELIGIBILITY AND WHAT REMAINS AS I SAID, STILL HOW THESE THINGS ARE GOING TO BE TRACKED. SO, IT IS IMPLEMENTED. IT'S WORKING. THERE HAVE BEEN FIVE DESIGNATION REQUESTS. THREE OF WHICH HAVE BEEN GRANTED. TWO NOT GRANTED. AND THERE ARE ACTUALLY VERY RECENTLY ONE VOUCHER AWARDED FOR THE TREATMENT OF MUCO POLYSACCHAROIDOSEIS. AND I THINK THAT THE FACT THAT THIS HAS HAPPENED IS REALLY AN EXTRAORDINARY ACHIEVEMENT AND DEMONSTRATION OF WHAT ADVOCACY CAN DO. I'M PARTICULARLY HOPEFUL THAT THE SECOND VOUCHER AWARDED WILL BE OR AT LEAST THE THIRD VOUCHER AWARDED WILL BE FOR A PRODUCT SPECIFICALLY FOR PEDIATRIC CANCER INDICATION. AND I THINK THERE ARE A NUMBER OF POTENTIAL DESIGNEES IN THE WING THAT IS HAVE EXPRESSED INTEREST IN THIS PROGRAM. SO I THINK THERE NEEDS TO BE SOME EXPANDED AWARENESS, MARKETING, IF YOU WILL, OF THE RARE PEDIATRIC DISEASE, PRIORITY REVIEWED VOUCHER PROGRAM. I THINK IT COULD BE PARTICULARLY APPLICABLE TO THOSE QUOTE/UNQUOTE, FAILED AGENTS, THOSE AGENTS THAT FAILED IN THE ADULT DEVELOPMENT ARENA FOR WHICH THERE IS INTEREST IN THE PEDIATRIC COMMUNITY AND IF THERE IS IN FACT EVIDENCE OF THEIR ACTIVITY. AS I MENTIONED EARLY COMMUNICATION, VERY EARLY. EXPRESSIONS OF INTEREST IN AGENTS FOR WHICH THERE IS A DESIRE TO DESIGN AND CONDUCT PHASE I STUDIES BETWEEN INVESTIGATORS, SPONSORS AND REGULATORS. I THINK THAT THERE IS CLEARLY AN OPPORTUNITY, AS THE AGENCY HAS REALLY PUT FORWARD A PATIENT-FOCUSED DRUG DEVELOPMENT PROGRAM, HAS BROUGHT IN FOCUS GROUPS FOR BREAST CANCER AND LUNG CANCER, AND I THINK HAVING ADVOCATES AS PART OF PREBLA, PRE-NBA, AND IND MEETINGS WITH THE AGENCY AND WITH THE MEDICAL OFFICERS WHO MAY NOT BE AS INFORMATIVE OR INFORMED OF PEDIATRIC CANCER, COULD REALLY BE HELPFUL. AS I MENTIONED, EARLIER, I THINK THAT THERE ARE OPPORTUNITIES TO RECONSIDER ANGLE GIABILITY REQUIREMENTS IN APPROPRIATE CIRCUMSTANCES IF THE CLINICAL INDICATION AND DISEASE BIOLOGY EXISTS. AND, THE GUIDANCE THAT IS BEING REWRITTEN FOR PEDIATRIC ONCOLOGY TRIALS CLEARLY SPECIFIES THAT PATIENTS BETWEEN 12-18 YEARS OF AGE DON'T NECESSARILY REQUIRE SPECIFIC PK STUDIES. WE DISCUSSED THE USE OF MASTER PROTOCOLS, BASKET PROTOCOLS, CLOUD PROTOCOLS, LOOKING AT THE SPECIFIC GENETIC DETERMINANTS TO GUIDE ENROLLMENT OR TO GUIDE TREATMENT ON A SINGLE PROTOCOL TREATMENT WITH A NUMBER OF INVESTIGATIONAL AGENTS. THIS IS OBVIOUSLY GOING TO REQUIRE SOME AGREEMENT TO COLLABORATE AND PARTICIPATE ON THE PART OF SPONSORS, BUT THERE IS PRECEDENT FOR DOING THIS. AND I THINK ENROLLING RELAPSED AND REFRACTARY PATIENTS, AND EVEN OTHER HIGH-RISK PATIENTS TO ADDRESS SOME OF OUR RISK ADVERSIVE BEHAVIOR, IS CLEARLY NECESSARY. I THINK HAVING TRIED TO OVERSEE THE DEVELOPMENT OF NEW TRIALS FOR RELAPSE AND REFRACTARY ALL AND THEIR INABILITY TO ACCRUE PATIENTS BECAUSE INVESTIGATORS WANTED TO KEEP GOING, KEEP GOING WITH WHAT WAS THOUGHT TO BE EFFECTIVE THERAPY, HAS TO REALLY CHANGE AND WE REALLY NEED TO LOOK AT WAYS TO CHANGE THIS WITHIN THE CLINICAL TRIALS INFRASTRUCTURE. LOOKING AT OPPORTUNITIES TO USE HISTORICAL CONTROL GROUPS AND SINGLE ARM TRIALS, ESPECIALLY WHEN THERE ARE LARGE EFFECT SIZES THAT ARE ANTICIPATED, AND AGAIN, WE NEED SOME EFFICACY INPUT INTO WHAT OUR AND WHAT CAN BE OR WHAT SHOULD BE RELEVANT ENDPOINTS WHEN WE DO TRIALS IN CHILDREN AND LOOK AT THE TRIAL DATA AS PART OF THE APPROVAL PROCESS. SO, I THINK THERE ARE WAYS FOR US TO WORK TOGETHER AND I'M HOPING THAT WE CAN DEFINITELY TAKE ADVANTAGE OF THOSE OPPORTUNITIES. >> I THINK WE SHOULD MOVE ON TO NANCY BECAUSE WE ARE RUNNING LATE HERE. AND I'M GOING TO ASK NANCY TO DISCUSS WHAT POINTS SHE WANTED TO MAKE AND HOPEFULLY WE'LL HAVE A LITTLE BIT OF TIME AT THE END FOR DISCUSSION. >> THANK YOU ALL SO MUCH FOR HAVING ME, INVITING ME TO SPEAK TODAY AND TO THE DCLG, THANK YOU FOR DECIDING TO FOCUS A WHOLE DAY ON PEDIATRICS. IT'S SOMETHING OUR COMMUNITY NEEDS. MY NAME IS NANCY GOODMAN. I'M FIRST AND FOREMOST A MOTHER OF A CHILD, JACOB, WHO DIED OFFING INULAR BLASTOMA FIVE YEARS AGO. >> CAN WE GET TO YOU PUT YOUR MICROPHONE CLOSER? I'M HAVING A HARD TIME HEARING YOU. >> THIS IS BETTER? >> YES. >> LET'S SEE. DO I HAVE TO LEAN FORWARD? >> USE BOTH. I'M GOING TO SIT DOWN OTHERWISE I HAVE TO DUCK. IS THIS PICKING UP MY VOICE? OKAY. I JUST WANT TO PUT A LITTLE BIT OF A HUMAN FACE ON THE EXPERIENCE OF PEDIATRIC CANCER. WHEN JACOB WAS DIAGNOSED AT AGE 8, HE WAS YOUR TYPICAL CUTE 8-YEAR-OLD BOY. WE THOUGHT HE WAS BRILLIANT. HE THOUGHT HE WAS GOING TO BE A PROFESSIONAL BASEBALL PLAYER OR A ROCK STAR MUSICIAN. TWO YEARS AFTER DIAGNOSIS, BY THE TIME JACOB DIED, HE WAS A CHILD IN A WHEELCHAIR WITH COGNITIVE DEFICITS, SPASTIC MOVEMENTS, HE HAD A G TUBE FOR FEEDING, HIS ENTIRE GI SYSTEM WAS NOT WORKING. THESE IMPAIRMENTS WERE NOT DUE TO THE CANCER, THEY WERE DUE TO THE TREATMENTS AND HAD JACOB SURVIVED, HE WOULDN'T HAVE BEEN ABLE TO LIVE INDEPENDENTLY. HE WOULDN'T HAVE BEEN ABLE TO GROW UP, HE WOULDN'T HAVE HAD A MINIMAL CHANCE OF MARRIAGE OR A JOB OR A FAMILY. AND I WANT TO TALK ABOUT THIS JUST TO UNDERSCORE THAT, PEDIATRIC CANCER IS A SERIOUS PROBLEM THAT HAS NOT BEEN SOLVED. KIDS ARE NOT BEING CURED. MANY KIDS DO GET THE 5 YEAR SURVIVAL RATE AND WE USE THIS SLOPPILY AND WE DESCRIBE IT AS A CURE BUT IT'S NOT A CURE. KIDS HIT THE 5 YEAR NUMBER AND MANY ARE QUITE SICK, MANY OF THEM DIE BEFORE THEY OTHERWISE WOULD HAVE IF THEY WERE TO LIVE A LONG AND HEALTHY LIFE AND THE GOAL, REALLY, FOR ALL OF US IS OUR CHILDREN LIVE A LONG, HEALTHY LIFE. I ALSO WANT TO TALK A LITTLE BIT ABOUT SOME OF THE TREATMENTS JACOB HAD. RADIATION. AND CRANIAL RADIATION. THAT COULD NEVER BE A CURATIVE TREATMENT. STEM CELL TRANSPLANTS THAT LEAVES KIDS PERMANENTLY IMMUNOLOGICALLY IMPAIRED. THIS ISN'T BE IN OUR BASKET OF TREATMENT FIST WE WANT TO CURE KIDS. WE HAVE SO MUCH WE NEED TO DO TO GET TO TREATMENTS THAT ARE APPROPRIATE FOR CHILDREN. I WANT TO TALK A LITTLE BIT ABOUT THE ROLE OF THE GOVERNMENT AND THE ROLE OF THE GOVERNMENT TO STEP IN AND PROVIDE PUBLIC SECTOR GOODS WHEN THE PUBLIC CANNOT. YOU KNOW, WE HAVE A, IN THE UNITED STATES, WE HAVE A PIPELINE FOR CANCER DRUGS OF ABOUT 900 DRUGS. YET THEY ARE ALMOST ALL ADULT CANCER DRUGS. THERE IS FEWER THAN A HANDFUL OF DRUGS FOR CHILDREN. SO, INDUSTRY REALLY IS NOT CONSIDERING PEDIATRIC CANCER DRUG DEVELOPMENT SERIOUSLY. AND I THINK THE NCI, FRANKLY, HAS NOT REALLY CONSIDERED THIS ISSUE IN A WAY THAT IS REALLY REFLECTIVE OF OUR SOCIETAL VALUES. AT THE NCI, WE THINK ABOUT THE BEST SCIENCE. THAT REALLY IS NOT IN A SOCIETY WHY WE CONSTITUTED THE NCI. WE SET UP THE NCI TO CREATE THE BEST SCIENCE TO SAVE PEOPLE. AND WHAT DOES THAT MEAN? THAT MEANS CREATING THE BEST SCIENCE WHEN INDUSTRY CAN'T. OR WHEN INDUSTRY IS UNWILLING TO DO SO. MAYBE THAT MEANS BASIC SCIENCE WHERE THE PAYOFFS ARE SO FAR IN THE FUTURE THAT COMPANIES JUST ANTICIPATOR WILLING TO ASSUME THAT KIND OF RISK. MAYBE THEY ARE MASSIVE PROJECTS THAT ARE DIFFICULT TO FINANCE IN THE PRIVATE SECTOR. ONER MAYBE THEY ARE PROJECTS FOR ORPHANED DISEASES LIKE PEDIATRIC CANCERS FOR WHICH THE MARKETS ARE SO SMALL THAT THERE IS NO OPPORTUNITY FOR RETURN ON INVESTMENT. AND I THINK THAT WHEN THE NCI INSTEAD PURSUES THE MOST EXCITING SCIENCE, IT IS PURSUING CANCER INDICATIONS THAT ACTUALLY ALREADY HAVE SUPPORT FROM THE PRIVATE SECTOR. AND THAT IS WHY THEY ARE AHEAD. THAT'S WHY THEY ARE THE MOST EXCITING. AND THEN WE USE OUR GOVERNMENT FUNDS TO SUPPLEMENT THAT. SO I THINK WE HAVE IT BACKWARDS. AFTER JACOB DIED, I FORMED KIDS VERSUS CANCER. AND THE QUESTION THAT I HAVE, WHICH I FIND MOST COMPELLING IS WHAT MECHANISMS MIGHT BE AVAILABLE TO ATTRACT PRIVATE SECTOR FUNDING TO PEDIATRIC CANCER? AS ALL OF YOU KNOW, OUR FIRST STEP OUT WAS THE CREATING HOPE ACT. I GET TO BE THE FACE OF THE CREATING HOPE ACT BUT IN FACT, THIS WAS TRULY A COMMUNITY WIDE EFFORT. PHYSICIANS AND ADVOCATES AND KIDS. AND ALL OF YOU IN THE ROOM NOW, KNOW FROM DR. REMANS VERY DETAILED AND EXCELLENT DESCRIPTION, HOW IT WORKS. WE ARE THRILLED TO ANNOUNCE THAT LAST WEEK, THE FDA DID AWARD A VOUCHER FOR -- WHICH CREATED -- THEY AWARDED THE FDA APPROVAL FOR THE DRUG FOR NUKEO POLYSACCHAROIDTOSIS, MPS4, THIS CREATED THE FIRST VOUCHER. SO WE ARE REALLY EXCITED. IT'S A TERRIBLE DISEASE. IT'S NOT PEDIATRIC CANCER BUT THESE KIDS WITH MTS4 CAN REALLY RIVAL OUR KIDS FOR SUFFERING AND FOR CHALLENGES THEY FACE AND I HOPE THAT THIS VOUCHER WILL BE SOLD. IT WILL BE SOLD AT A EXCITING EVALUATION THAT WILL DRIVE MORE COMPANIES INTO PEDIATRIC CANCER DRUG DEVELOPMENT. WE ARE TALKING TO INVESTMENT BANKS WHO HAVE BEEN WILLING AND EAGER TO MAKE A MARKET IN VOUCHERS. SO WE ARE REALLY EXCITED ABOUT FACILITATING THE TRANSFERABILITY OF THESE VOUCHERS. NOW NOTWITHSTANDING THE EXCITING DEVELOPMENT, THERE ARE SOME CONCERNS WE HAVE WITH RESPECT TO THE FDA IMPLEMENTATION OF THE CREATING HOPE ACT. AND WE HAVE NOT HAD DETAILED CONVERSATION BUSY THIS YET, IN PARTICULAR, WE ARE CONCERNED ABOUT THE FDA'S DEFINITION OF WHAT KIND OF PEDIATRIC DISEASE DRUGS WOULD TRIGGER THE CREATION OF A VOUCHER AS DR. REMAN DESCRIBED. THESE WOULD BE DRUGS THAT TREAT INDICATIONS FOR WHICH 50% OF THE INDIVIDUALS WITH THIS DISEASE, THE 50% OF THE PREVALENCE ARE PEOPLE 18 YEARS OF AGE OR YOUNGER. AND OUR CONCERN IS WHETHER THAT MIGHT EXCLUDE MOST PEDIATRIC CANCERS. DR. REMAN IS SHAKING HIS HEAD. I'M HOPING A A GIANT MISUNDERSTANDING HERE WHICH HE IS HAPPY TO JUMP IN. YES? OKAY. THAT WOULD BE GREAT. BUT, FOR MANY CANCERS, PEDIATRIC CANCERS WHICH MAY APPEAR IN ADD LES EXPENSE IS HAVE HIGH SURVIVAL RATES, GETTING THE PREVALENCE NUMBER OVER 50% COULD BE CHALLENGING. SO WE LOOK FORWARD TO ADDITIONAL COMMUNICATIONS FROM THE FDA AND ASSURANCES THAT WILL NOT EXCLUDE PEDIATRIC CANCERS. OF COURSE, THE PURPOSE OF THE CREATING HOPE ACT WAS TO ADDRESS MARKET FAILURES AND WE CERTAINLY HERE IN THIS AM RADIO, KNOW THAT WITH RESPECT TO DRUG DEPARTMENT OF PEDIATRIC CANCER INDICATIONS, THERE HAVE BEEN SERIOUS MARKET FAILURES. NOW THAT THE CREATING HOPE ACT HAS BEEN ENACTED INTO LAW AND VOUCHERS ARE BEING CREATED, WE HAVE BEGUN TO TALK TO VENTURE CAPITAL FIRMS TO ASK WHETHER AND HOW ONE CAN START CONSIDERING FOR PROFIT STRATEGIES TO DEVELOP DRUGS FOR PEDIATRIC CANCERS. AND WE HAVE ACTUALLY HAD VERY SPECIFIC CONVERSATIONS WITH SPECIFIC DRUG CANDIDATES. THERE ARE TWO LINES OR STRATEGIES THAT ONE CAN PURSUE HERE. THE FIRST STRATEGY IS DR. REMAN SUGGESTED IS REPURPOSING OR RESCUING. AND THE QUESTION HERE IS, IF YOU CAN TAKE A DRUG THAT WAS DEVELOPED FOR AN ADULT CANCER INDICATION, AND FOR WHICH A PHARMACEUTICAL COMPANY MIGHT HAVE PUT IN $100 MILLION OR MORE DOLLARS INTO. AND PERHAPS THIS DRUG FAILS IN PHASE II OR PHASE III, PERHAPS IT DOESN'T DEMONSTRATE THE EFFICACY THAT WOULD WARRANT FDA APPROVAL ON THE ADULT INDICATION, BUT, PERHAPS IT DEMONSTRATES VERY EXCITING EVIDENCE ON THE PEDIATRIC INDICATION. IS THERE A WAY WE CAN ENCOURAGE THE PHARMACEUTICAL COMPANY TO STAY IN THE GAME AND CONTINUE TO DEVELOP THE DRUG FOR KIDS WITH CANCER? IN PARTICULAR, THIS WAS AN ISSUE THAT THE WHOLE COMMUNITY GRAPPLED WITH WHEN LEE HELLMAN'S EXCITING TRIAL FOR IGFR INHIBITORS WAS STOPPED BEFORE THE CONCLUSION OF HIS TRIAL BECAUSE THE ADULT TRIALS FAILED AND THE PHARMACEUTICAL COMPANY DECIDED TO ENTIRELY DISCONTINUE PROVIDING CLINICAL SUPPLY OF THE DRUG. SO, IT'S A REALLY -- MAYBE IT WOULD TAKE 5 OR 10 MILLION DOLLARS TO TAKE THIS DRUG AND CARE AT THE THROUGH ALL THE WAY TO FDA APPROVAL ASSUMING IT WARRANTED IT. AND MAYBE WITH THE INCENTIVES EMBEDDED IN THE CREATING HOPE ACT, WITH PREMIUM PRICING, WHICH I REALIZE MANY OF US ARE AMBIVALENT ABOUT, BUT NEVERTHELESS CONSTITUTE INCENTIVE, MAYBE WE CAN CREATE A WAY FOR DUMPS CONTINUE TO DEVELOP THESE DRUGS, OR, WE CAN GIVE THEM A REASON TO TRANSFER THE INTELLECTUAL PROPERTY OF THESE DRUGS TO THIRD PARTIES WHO WILL BE WILLING TO DEVELOP THEM. THE SECOND PATH TOWARDS DRUG DEPARTMENT, OF COURSE, IS VERY EXCITING ONE WHICH IS REALLY DEVELOPING DRUGS FROM SCRATCH FOR KIDS WHO HAVE CANCER, IDENTIFYING UNIQUE PEDIATRIC CANCER TARGETS THAT DO NOT EXIST IN ADULT INDICATIONS. AND HERE WHAT IS INTERESTING, IS A VENTURE CAPITAL FIRM WE SPOKE TO SAID THEY WOULD BE INTERESTED IN DEVELOPING DRUGS HERE. THE TARGETS HAVE TO BE DRUGABLE, WHICH IS HARD FOR PEDIATRIC CANCERS, AND IT HAS TO BE A SMALL MOLECULE DRUG. SO, THE ISSUE HERE INTERESTINGLY, IS THAT IMMUNOTHERAPIES ARE VERY EXPENSIVE TO DEVELOP. AND HERE IN LIES WHAT WE ALL ARE GOING TO SEE AS ONE OF THE LIMITATIONS OF PRIVATE SECTOR DEVELOPMENT OF PEDIATRIC CANCER DRUGS. AND THAT IS, NO MATTER WHAT THE INCENTIVES WE MIGHT CREATE, AT SOME POINT, IT MIGHT JUST BE TOO EXPENSIVE TO DEVELOP DRUGS FOR CHILDREN. TO THIS END, WE ARE REALLY HAPPY THAT DR. SMITH AND CTIP STEPPED IN AND ACTED AS SUPPLIER MANUFACTURER OF DRUGS ON A COUPLE OF OCCASIONS. C14 AND 18 AND ALSO NOW THIS IGF1R INHIBITOR, FOR IMMUNOTHERAPIES. WE HAVE TO BE REALLY CAREFUL. I HOPE THE DCLG IS, YOU KNOW, IS REALLY TAKING THIS AS A POSITIVE AND ENSURES THIS PROGRAM IS FULLY FUNDED SO ANY OTHER CANDIDATES WE FIND THAT NEED TO BE DEVELOPED CAN BE ANDY WOO ARE NOT JUST WAITING FOR 5 OR 10 OR 15 MILLION DOLLARS HERE OR THERE WHEN THAT IS THE ONLY WAY WE WILL DEVELOP THESE DRUGS FOR THESE KIDS. SO, WE DO HAVE THESE OPPORTUNITIES. WE ARE SEEKING TARGETS. WE ARE SEEKING CANDIDATES THAT MAY MERIT FOR PROFIT DRUG DEVELOPMENT, BUT AND WE THINK WE WILL FIND SOME EXCITING CANDIDATES WE THINK THERE WILL BE SOME EXCITING STEPS WE'LL TAKE. BUT, EVEN WITH AS MUCH EFFORT AS WE TAKE, THE FACT IS THAT AT THE END OF THE DAY, PRIVATE INDUSTRY WILL ONLY GO SO FAR WHEN IT COMES TO THE INDICATIONS LIKE PEDIATRIC CANS CHER HAVE TINY MARKETS AND -- CANCER -- AND DRUG DEVELOPMENT IS REALLY HARD AND WHEN IF IS IMMUNOTHERAPIES, THEY ARE VERY, VERY EXPENSIVE. AND SO TO THIS END, WE REALLY HOPE THAT THE NCI JUST REMEMBERS ITS ROLE, WHICH IS THAT OF A GOVERNMENT INSTITUTION PROVIDING A PUBLIC SECTOR GOOD WHEN PRIVATE INDUSTRY CANNOT DO SO. SO, A COUPLE OF OTHER THINGS. HOW TO FIND THE TARGETS. ONE OF THE QUESTIONS IS FOR WITH RESPECT TO REPURPOSING. HOW DO YOU KNOW WHICH PEDIATRIC INDICATIONS WOULD BENEFIT FROM DRUG DEVELOPMENT OF AN ADULT DRUG? AGAIN, DR. SMITH'S PPTP PROGRAM, WHICH IS A PANEL OF CELL LINES THAT ARE USED TO SCREEN DRUGS DEVELOPED FOR ADULTS INDICATIONS, TO SEE IF ANY HAVE BOST KIDS WITH CANCER, IT'S A GREAT PROGRAM. IT'S ALSO A TINY PROGRAM. I THINK IT'S FEWER THAN 50 CELL LINES. AND JUST TO GIVE YOU A COMPARISON, WE ARE WORKING WITH A NONPROFIT DOING A LARGER VERSION OF THIS FOR ALL SORTS OF ADULT CANCERS. FOR COLORECTAL CANCER ALONE, THEY HAVE 2000 CELL LINES. AND WE HAVE 50 FOR EVERY PEDIATRIC CANCER. SO, YOU KNOW, CAN WE REALLY FIND OR GLEAN ALL THE INFORMATION THAT IS BENEFICIAL TO KIDS WITH CANCER IF HAVE YOU SUCH A SMALL PROGRAM? IT NEEDS TO BE MUCH, MUCH BIGGER. WE ARE SO GRATEFUL, I'M SO GRATEFUL FOR ALL THE EFFORT DR. SMITH PUT INTO GATHERING RESOWSES AT THE NCI, BUT IT'S NOT ENOUGH. SIMILARLY, WHO IS GOING TO DO THE CLINICAL TRIALS? WE HAVE CHILDREN'S ONCOLOGY GROUP, WHICH IS AS WE ALL ACKNOWLEDGE A GREAT RESOURCE, BUT THE 4000 DOLLARS PER CHILD AND THE NCI BUDGET FOR ACCRUING KIDS ON TRIALS. THIS IS NOT ENOUGH TO DO REGISTERED TRIALS LEADING TO FDA APPROVAL. JUST TO GIVE YOU A COMPARISON OF HOW MUCH THAT COSTS, IN THE LUNG MASTER PRO PROTOCOL BEING CONDUCTED BY ONE OF THE ADULT CONSORTIUMS T IS GETTING 4000 DOLLARS FOR A PATIENT AND THEN INDUSTRY IS THROWING IN $35 PER PATIENT TO DO MONITORING AND REGULATORY COMPLIANCE. AND WHERE IS THAT GOING TO COME FROM IF COG NEEDS THAT TO ALSO DEVELOP DRUGS TO PUT TOGETHER TRIALS THAT WOULD MEET STANDARDS FOR FD AMOUNT APPROVAL? WE ARE ASSUMING AS A SOCIETY THAT INDUSTRY WILL STEP IN AND PAY THAT FOR PEDIATRIC TRIALS AS WELL BUT THAT IS A BIG QUESTION MARC AND I THINK WE REALLY NEED TO ADDRESS THIS AS A COMMUNITY AND LOOK FOR PUBLIC FUNDS TO DRAMATICALLY INCREASE COG SUPPORT GIVEN THAT IT IS JUST NOT GOING TO BE EASY TO RAISE THESE FUNDS FROM INDUSTRY. SO, I KNOW, I WANTED TO CONCLUDE AND I KNOW THAT PREVIOUS SPEAKERS HAVE TALKED ABOUT WHAT THE ADVOCATES CAN DO. WE ALL -- THE ADVOCATES ARE INCREDIBLY SMART AND WE ALL TALK TO EACH OTHER ALL THE TIME AND WE WILL CONTINUE TO DO THAT AND THINK ABOUT WHAT WE WANT TO DO. BUT WE ARE HERE FOR THE FIRST TIME MEETING ALL OF YOU AT DCLG AND I'D LIKE TO PROPOSE A FEW THINGS WE HOPE YOU MIGHT CONSIDER DOING. FIRST, IN YOUR INDIVIDUAL ORGANIZATIONS, TAKE ON PEDIATRICS AS ONE OF YOUR PROJECTS. IF YOU'RE WORKING WITH COMPANIES DEVELOPING DRUGS FOR YOUR INDICATIONS, ASK THEM WHY THEY ARE NOT LOOKING AT THESE DRUG PRODUCTS FOR PEDIATRIC INDICATIONS AS WELL. AND PLEASE BE A FORCE WITH US IN PUSHING FOR SINGLE INDs OR PEDIATRIC TRIALS AS WOULD BE NECESSARY. IF YOU'RE DOING OTHER PROJECTS WHETHER IT BE VENTURE, PHILANTHROPY, BIOREPOSITORIES, PARTNER WITH A PEDIATRIC ADVOCATE AND MAKE US SMARTER AND SOPHISTICATED SO WE CAN BRING NEW KNOW HOW INTO THE PEDIATRIC SPACE. INSTITUIONAL REFORMS AT THE NCI. THIS WAS AN IDEA PROPOSED TO ME BY RUTH HOFFMAN SO I WON'T CLAIM CREDIT FOR IT. BUT LET'S GET A PEDIATRIC ADVOCATE ON EVERY PATIENT ADVOCATE BOARD AT THE NCI SO THAT WE REALLY CAN ENSURE GOING FORWARD THAT WE HAVE APPROPRIATE REPRESENTATION AND WE BRING UP THESE ISSUES. I'M SO GRATEFUL THAT DAVID ARONS AND MAX WALLACE AND PERHAPS OTHERS OF YOU HAVE SPECIFIC PEDIATRIC CANCER PROJECTS. THANK YOU. BUT WE EVEN NEED A PETE AT RICK ADVOCATE ON THE DCLG. WE NEED ONE ON OTHER PANELS AND PLEASE BE OUR VOICE AND PUSH FOR INCLUSION OF OUR COMMUNITY IN AS MANY OF THE ADVOCACY BOARDS AS POSSIBLE. AND THIRD, GENERALLY, I HOPE YOU WILL BEGIN A CONVERSATION WITHIN THE NC-I TO TALK ABOUT WHAT THE PURPOSE OF THE NCI IS, HOW WE WANT TO SUPPORT THE BEST SCIENCE BUT IT IS THE BEST SCIENCE TO SAVE LIVES, WHEN PRIVATE INDUSTRY CAN'T OR WON'T STEP IN TO PROVIDE THAT FUNDING. AND THAT FOR OUR MOST TREASURED AND VALUABLE MEMBERS OF OUR SOCIETY, OUR KIDS, AND FOR INSTANCES IN WHICH THESE KIDS ARE AFFLICTED BY RARE DISEASES FOR WHICH IT IS VERY TOUGH TO PULL INDUSTRY IN, I REALLY HOPE THAT THERE WILL BE EXTRA CONCERN AND EXTRA INTEREST WITH RESPECT TO NCI FUNDING. IT'S NOT JUST ABOUT THE SCIENCE. IT'S ABOUT SAVING WHEN PRIVATE INDUSTRY KEPT. THANK YOU VERY MUCH. [ APPLAUSE ] >> SO I HAVE BEEN TOLD BY MAX WE HAVE A LITTLE TIME FOR DISCUSSION. IS THAT RIGHT? WHAT WE ARE GOING TO DO IS NOT INCLUDE THAT LAST MODULE THAT WAS DCLG-SPECIFIC MODULE UNRELATED TO THIS. WE'LL JUST PITCH THAT AND DO IT AT THE NEXT MEETING SO WE ADD MORE TIME FOR THIS BECAUSE DISCUSSION IS IMPORTANT AND WE OUGHT TO ENABLE IT TO FULLY FLOWER. >> SO LET ME FOLLOW-UP WITH YOU GREG ON THE NANCY'S COMMENT. THE INTERPRETATION OF PRIMARILY EFFECTIVE AND THE DECISION TO USE PREVALENCE, I THINK THE ISSUE THEN IS DO SURVIVORS OF A DISEASE COUNT IN THE PREVALENCE FIGURES? IF THEY DO, THAT IS GOING TO BE A POTENTIAL PROBLEM? >> UNFORTUNATELY, THE INTERPRETATION WAS THE 50%. THE PREVALENCE IS NOT INTERPRETATION BUT THE PREVALENCE IS WHAT IS USED BY THE OFFICE OF ORPHAN PRODUCT DEVELOPMENT TO DEFINE ORPHAN AND RARE IN THAT INCIDENCE. SO, IT WASN'T SOMETHING THAT WE HAD A CHOICE IN USING, QUITE HONESTLY, AND I TRIED VERY HARD TO SAY, PREVALENCE. WE DON'T WANT TO USE PREVALENCE. WE WANT TO USE INCIDENCE. EVEN WITH THAT, IT IS UP TO 50%. IT DOESN'T HAVE TO BE. IT COULD BE MORE THAN 50%. BUT TO ANSWER YOUR QUESTION SPECIFICALLY, YES, IT WOULD INCLUDE PATIENTS IN HAVE THE DISEASE AT A GIVEN POINT IN TIME. SO IT INCLUDES PEOPLE THAT ARE CURED OF THE DISEASE. SO A RECENT EXAMPLE TOOK SOME MAJOR WORK ON MY PART, LOOKING AT THE SEER DATABASE FOR A DISEASE WHICH IS LISTED BUT INCLUDES LOTS OF OTHER RELATED ABNORMALITIES. NOT NECESSARILY RELATED TO THE DISEASE. BUT THAT IS IN THE DATABASE AND THAT IS WHAT YOU DO. SO I THINK THERE ARE OPPORTUNITIES TO LOOK AT OTHER SOURCES OF DATA WITH RESPECT TO PREVALENCE AND I THINK NOW THAT THERE HAS BEEN EDUCATION ON THE PART OF THE OOPD, WHICH IS THE GROUP THAT HAS BEEN GIVEN THE RESPONSIBILITY FOR MAKING THESE DESIGNATIONS, THAT'S -- I THINK WE ENLIGHTENED THEM TO THE POINT WHERE I DON'T THINK THIS IS AN ISSUE. AND IF IT IS, THERE ARE OPPORTUNITIES TO APPEAL IT AND DISCUSS IT. >> SO WHAT YOU'RE SAYING NOW, THAT ASSUMES THE BIOLOGY OF ADULT TUMORS AND PEDIATRIC TUMORS -- >> NO. THESE AREN'T NECESSARILY ADULT TUMORS. THESE ARE PEOPLE WHO HAD ADULT OR HAD PEDIATRIC CANCERS BUT WHAT WAS SELECTED TO LOOK AT WERE 10-YEAR PREVALENCE RATES AND THERE WERE MANY CURED SURVIVING -- >> WE HAVE 330,000 CHILDHOOD CANCER SURVIVORS WHICH WILL BLOW AWAY PEDIATRIC PREVALENCE. >> I THINK THERE IS A WAY TO LIMIT THE PERIOD OF TIME THAT THE OFFICE USES. >> RIGHT. >> SO THAT -- >> [ OFF MIC ] >> SO, EVEN IF WE ARE NOT TALKING ABOUT SURVIVORS, IF YOU'RE TALKING ABOUT GLOWO BLASTOMAS, THE BIOLOGY OF PEDIATRIC IS VERY DIFFERENT FROM ADULT. >> I DON'T DISAGREE. THE LAW WAS WRITTEN THE WAY THE LAW WAS WRITTEN. AND I THINK THERE ARE WAYS, AS I JUST DESCRIBED, TO AMEND, REPEAL, DECISIONS THAT ARE MADE THAT JUST WERE PREPOSTEROUS TO ME. SO, IT CAN BE WORKED AROUND. I DON'T SEE THIS AS A HUGE DEAL QUITE HONESTLY. >> SO, ON A DIFFERENT TOPIC SO IF SOMEBODY ELSE WANTS TO SPEAK ON THIS TOPIC? WHEN YOU TALK ABOUT GENOMIC CLASSIFICATION AND HOW STUDIES WILL BE DIFFERENT WHEN WE START TO LOOK ACROSS GENOMIC CLASSIFICATIONS, IT MAKES ME WONDER IF THERE IS ANY POSSIBILITY FOR NOT ONLY THE SORT OF HORIZONTAL INTEGRATION LOOKING AT DIFFERENT TUMOR TYPES THAT MIGHT HAVE THE SAME GENETIC ABNORMALITY BUT A VERTICAL INTEGRATION WHERE YOU IF HAVE YOU THAT ABNORMALITY NECHILDREN, IS THERE A WAY TO WRITE THAT INTO THE ADULT PROTOCOL THAT IS MEANINGFUL? >> I WOULD THINK THAT -- I MEAN, WHAT I SEE POTENTIALLY HAPPENING IS THAT DRUGS WILL BE DEVELOPED BASED ON PATHWAYS AND WHETHER YOU HAVE BREAST CANCER, LUNG CANCER OR MELANOMA. YOU MIGHT BE ELIGIBLE FOR A TRIAL. IF WE HAVE NEUROBLASTOMA ORUINGS SARCOMA, YOU COULD BE POSSIBLY BE ELIGIBLE FOR THAT. >> BUT THAT IS GOING TO TAKE A LITTLE BIT OF TIME. I DON'T THINK PHARMACEUTICAL INDUSTRY IS NECESSARILY THERE YET WITH PATHWAY-FOCUSED OR TARGET-FOCUSED DRUG DEVELOPMENT. THERE IS STILL SOME TENSION TWO SPECIFIC DISEASES. EVERY LARGE DISEASE INDICATION COMES DIVIDED INTO SMALLER AND SMALLER SUBSETS AND MORE NUMEROUS SUBSETS. IT MAY JUST HAPPEN. AND I THINK THAT WOULD BE AN OPPORTUNITY THAT PEDIATRIC ONCOLOGY COULD -- [ INDISCERNIBLE ] >> SO JUST THIS PAST NOVEMBER, THE ACR SPONSORED A MAJOR CONFERENCE ON PEDIATRIC CANCER. DR. HELMAN WAS A CO-CHAIR OF THAT AS WAS DR. MAREIS. HOW CAN THAT KIND OF EVENT, MEETING, CONFERENCE, HELP IN TERMS OF ATTRACTING INDIVIDUALS TO THE FIELD, IDENTIFYING SCIENTIFIC OPPORTUNITIES, AND SHOULD WE JUST CONTINUE THAT AND MAYBE THIS WILL HELP PRIME OF PUMP SO TO SPEAK GOING FORWARD? >> I UNFORTUNATELY COULDN'T BE THAT THE CONFERENCE. BUT ABSOLUTELY. IT'S NOT JUST WHERE DOES PEDIATRIC FALL ON THE NCI RADAR SCREEN, WHERE DOES IT FALL ON ASCO, ALLS, AND IT IS RISING. THERE IS COMMITMENT FROM THE TOP LEVELS. AND THAT IS A PLUS. IN PART, BECAUSE IT BROADENS THE COMMUNITY OF SCIENTISTS WHO ARE COLLABORATING. BECAUSE THE SCIENTIFIC QUESTIONS AS JOHN POINTED OUT, WHEN HE SHOWED THE NUMBER OF MUTATIONS AS A FUNCTION OF CANCER THAT OCCURS IN AGE, WE HAVE A LOWER SIGNAL TO NOISE RATIO IN MANY PEDIATRIC CANCERS. THAT SCIENTIFICALLY CAN BE INTERESTING. SO I DO THINK IT IS VERY HELPFUL BUT AT THE END OF THE DAY, IF THERE IS NO FUNDING TO GO AFTER, IT IS JUST GOING TO BE AN INTERESTING MEETING. >> I WASN'T ABLE TO GO EITHER BECAUSE THERE WAS NO FUNDS AVAILABLE FOR TRAVEL AT THE FDA. SO I FELT BAD THAT I MISSED IT. BUT I THINK IT IS ALSO AN OPPORTUNITY NOT ONLY TOW BRING COLLABORATING SCIENTISTS TOGETHER BUT TO BRING INDUSTRY SCIENTISTS AND INDUSTRY TOGETHER BECAUSE I THINK 234 LARGE PART, THEY ARE UNAWARE OF SOME OF THESE VERY IMPORTANT AND RECENT FINDINGS. BUT I THINK -- AND MAYBE INVESTMENT BANKERS OR VENTURE CAPITALISTS -- CERTAINLY PEOPLE FROM INDUSTRY. THEY ARE PRETTY CREATIVE ABOUT LOOKING FOR WAYS TO CREATE MARKETS THAT MIGHT EXIST. >> JUST SO PEOPLE -- I PROMISED NANCY I WOULD TALK ABOUT THIS. JUST SO PEOPLE UNDERSTAND THE MAGNITUDE OF THE PROBLEM. SO I SPENT 20 YEARS STUDYING IGF PATHWAY AND WE FINALLY HAVE THESE AS SOMEONE SAID, THERE WEREN'T JUST WONG. THERE WERE 10 COMPANIES THAT HAD THESE IGF1 RECEPTOR ANTIBODIES AND THEY STUDIED THEM IN BREAST AND LUNG AND PANCREATIC. NONE OF WHICH RESPONDED WITH A SINGLE AMOUNT BUT THEY WERE ALREADY DOING COMBINATIONS. RIGHT AWAY. IN FACT, THERE WAS A SIGNAL IN COMBINATION AND LUNG CANCER SO THEY DID A DEFINITIVE PHASE III STUDY THAT COMPLETELY FAILED. THAT COMPANY SAID, WE ARE DONE. SO, AS MALCOLM SAID, SO OUR STUDY GOT CLOSED BEFORE WE EVEN HAD THE RIGHT DOSING SCHEDULE. AND WE SAW ABOUT A 14-15% RESPONSE RATE. BUT SOME OF THOSE PATIENTS WERE ON STUDY SINGLE DRUG, MULTIPLY RECURRENT VIEWING FOR 3-4 YEARS WITHOUT DISEASE REOCCURRENCE. IN BREAST CANCER THAT WOULD HAVE GONE SOMEWHERE. BUT, WHEN THE NCI WAS NEGOTIATING WITH AMGEN, AND AMGEN WAS RUNNING THE PANCREATIC CANCER STUDY, IT FAILED. AND I CALLED MALCOLM UP. I SAID, THEY WON'T GIVE YOU THE DRUG EVEN THOUGH THEY SAID THEY WOULD. AND SURE ENOUGH THEY SAID WE ARE DONE. SO, FOR ALL THIS TIME, WE COULDN'T GET ANY. THEY WERE ALL DONE. SO CTAP WAS SO INNOCENCED AND JEFF ABRAHAMS, HE CALLED UP AMGEN AND SAID, HOW CAN YOU DO THIS? SO WHAT AMGEN AGREED TO DO WAS SELL TO THE NCI BULK -- SO ANTIBODIES, MONOCLONAL ANTIBODIES MADE IN THE BIOREACTORS YOU GROW. SO THEY SOLD THIS BULK THING WHICH THE NCI WILL HAVE TO SPEND MILLIONS OF DOLLARS TO MAKE A GMP GRADE ANTIBODY THAT CAN BE GIVEN TO HUMAN BEINGS. AND HAVING WORKED ON THIS, I HAVE A COUPLE OF IDEAS FOR REALLY NICE COMBINATION THAT IS WE SHOWN ARE MUCH MORE EFFECTIVE THAN SINGLE DRUG OF XENOGRAPHS. AND AMGEN THEN TOLD THE NCI, YOU CAN ONLY DO THIS ONE STUDY. CHEMOTHERAPY PLUS THIS ANTIBODY. WE WILL NOT ALLOW YOU TO DO A SINGLE OTHER STUDY. EVEN THOUGH THE NCI IS PUTTING IN 5 MILLION DOLLARS. SO, I MEAN, THIS IS A REAL PROBLEM BECAUSE IT HAD -- THIS IS MY FIRST BRUSH UP WITH A DRUG THAT HAD NO IMMEDIATE INDICATION OF ANY ADULT CANCER BUT IT HAD ACTIVITY IN A PEDIATRIC CANCER. AND IT IS A TOUGH ROW TO HO. AND I JUST -- PEOPLE DON'T REALIZE HOW DIFFICULT IT IS. AND NANCY SAID, WE HAVE SOME ADVOCATES IN THE PHARMACEUTICAL INDUSTRY BUT THEY ARE LOOKING FOR SMALL MOLECULES, KINASE INHIBITORS AND UNFORTUNATELY, MANY OF THESE TUMORS ARE NOT KINASE DRIVEN. AND I THINK WE WILL HAVE MORE -- WE'LL PROBABLY MAKE MORE IMPROVEMENTS WITH NONKINASE INHIBITORS AND I JUST DON'T KNOW HOW WE'LL GO FORWARD. IT'S A REAL ISSUE. AND WHATEVER ADVOCATES CAN DO TO HELP US HERE, WE NEED HELP BECAUSE WE ARE NOT DEALING WITH THIS PROBLEM. >> MY FIRST COMPANY WAS AN HI AIDSUM AND WE ALL LOOKED AT HOW QUICK THAT MARKET MOVED AND IT WAS ALMOST DIRECTLY PROPORTIONAL TO HOW MANY PEOPLE CHAINED THEMSELVES TO THE RAILINGS ON THE ENTRANCE TO THE EXECUTIVE SUITES OF THE PHARMACEUTICAL COMPANIES. AND NOT THAT YOU CAN DO THAT. I WOULD NEVER ADVOCATE THAT NCI SHOULD DO THAT, BUT I DO FEEL THAT SOMETIMES OUR ADVOCACY COMMUNITY IS WAY TOO POL II LIGHT WITH HOW WE DEAL WITH INDUSTRY. SOMEBODY SHOULD HAVE BEEN RAILING IN PUBLIC N COLUMNS AND NEWSPAPERS AND MAGAZINES ABOUT THE AMGEN'S DECISION. >> I WOULD JUST POINT OUT AND THEN I'LL SHUT UP. PHARMACEUTICAL COMPANIES AREN'T SO DARN SMART. IN THE 1960S, THERE WASN'T A SINGLE BOOK. ANTI-CANCER DRUGS WERE NOT VIABLE. THEY WEREN'T INTERESTED. WHICH IS ONE OF THE REASONS THE 1970s, THE CANCER ACT HAPPENED. BECAUSE FARMY DIDN'T SEE ANTI-CANCER DRUGS AS FINANCIALLY LIABLE. SO JUST BECAUSE IN 2014, A DRUG FOR PEDIATRIC CANCER ISN'T FINANCIALLY VIABLE T DOESN'T MEAN IT WON'T BE IN THE FUTURE. THEY ARE NOT SO DARN SPARK SMART. AND NOW IT'S ONE OF THE BIGGEST MONEYMAKERS. IN 1970s, IT WAS NOT. THEY WOULDN'T MAKE ANYTHING. >> SO THIS IS A PUBLIC MEETING. >> I SHOULD HAVE BEEN THE ONE TO SAY THAT. >> IF YOU WANT TO CLARIFY AND BUILD UPON THE STORY, FIRST, THE BAD NEWS PART OF IT, WE HAD A TRIAL OR WE HAVE A TRIAL THAT LITERALLY HAS BEEN READY TO GO OVER FOR OVER THREE YEARS WAITING FOR ANTIBODY. THERE WAS A LONG LIST OF COMPANIES IN THAT SPACE AND A NUMBER OF THOSE WE HAD PEDIATRIC DATA. SO, TO AMGEN'S CREDIT, THEY ARE THE ONLY COMPANY WHO WAS WILLING TO DO THIS AND JUST TO CLARIFY IT, THEY DID TAKE A CALL TO THE CEO FROM SOMEONE, BUT IF YOU GET THROUGH, YOU CAN HAVE AN IMPACT. AND IT WAS A CONCERTED EFFORT BETWEEN MANY, MANY PEOPLE. I DON'T THINK THEY SOLD DRUGS BUT THE COST OF TAKING THE BULK SUBSTANCE AND MAKING IT INTO A DRUG WERE FULLY BORN BY THE NCI. BUT THERE IS A LONG LIST OF COMPANIES THAT SIMPLY WOULD NOT ENTER INTO THE DISCUSSION FOR PEDIATRIC DEVELOPMENT. ONLY ONEAL BEE IT IN A LIMITED AND CHALLENGING WAY, THAT DID IT. >> LAWYERS ARGUE FROM HYPERBOLE. SO, IT WAS EASY FOR ME TO DO THE, CHAIN YOURSELF TO THE RAIL. BUT I DO THINK THAT -- [ LAUGHS ] DO I THINK THE ADVOCATES SHOULD RECOGNIZE IN MANY CASES, COMPANIES DO RESPOND TO PUBLIC SUGGESTIONS. AND THAT IT ISN'T JUST A QUIET DECISION IF YOU HAVE A DOG IN THE FIGHT. AND THERE ARE POLITE WAYS TO DO IT BUT I THINK IT'S AN ACTIVE ROLE FOR THE ADVOCACY COMMUNITY: WE CAN DO IT BECAUSE WE ARE INTERESTED IN THIS IN A WAY WHERE WE HAVE FREEDOM OF ACTION. I AGREE. >> AND THEY MIGHT RYE SPOND IN THAT INSTANCE NOT ONLY BECAUSE OF PUBLIC OUTCRY BUT BECAUSE IT CHANGES THE ECONOMIC MODEL. IN SOME WAYS. >> I WANTED TO MAKE A COMMENT SINCE WE Z SOME OF THE WORLD'S GREATEST RESEARCHERS IN THE ROOM. IN THE ROOM HERE IS ORGANIZATIONS THAT LITERALLY REPRESENT MILLIONS OF FAMILIES TOUCHED BY CHILDHOOD CANCER. THE ALLIANCE FOR CHILDHOOD CANCER IS WELL REPRESENTED HERE. AND SO, ONE OF THE THINGS THAT WE, AS PERSONAL AND PROFESSIONAL ADVOCATES ARE ALWAYS SEEKING IS WE HAVE VOLUNTEERS AND DONORS THAT ARE SAYING, WE WANT TO ADVOCATE BUT WE REALLY WANT TO KNOW WHAT IS THE AGENDA? WE'LL ADVOCATOR WHATEVER YOU TELL US TO ADVOCATE FOR. OUR JOB IS FIGURING OUT WHAT IS THAT REALLY CRISP AGENDA? WHAT IS THE PRIORITY? WE DISCUSSED A LOT OF THINGS TODAY. WE DISCUSSED THINGS THREE DIFFERENT CATEGORIES AT LEAST. INCREASING GOVERNMENT INVOLVEMENT, IMPROVING SCIENCE FOR CLINICAL CARE AND INCREASING AND IMPROVING INDUSTRY INVOLVEMENT. WE TALKED ABOUT BIOPSIES, LACK OF A MAJOR NCI INITIATIVE. REGULATORY ISSUES, FUNDING, FLEW TRIAL DESIGNS, NEW TRIAL DESIGNS, CONCENTRATED EFFORTS TO MINIMIZE TOXICITY. AND PRECLINICAL MODEL DEVELOPMENT AND INCENTIVES FOR INDUSTRY. THAT'S A HUGE AGENDA OF A LOT OF DIFFERENT INTERRELATED PARTS. SO WHAT ADVOCACY GROUPS SEEK IS TO REALLY KNOW ULTIMATELY WHAT IS GOING TO -- WHAT ARE THE BARRIERS THAT EXIST TODAY THAT IF DONE AWAY WITH ARE GOING TO BE THE BIGGEST BANG FOR OUR BUCK? WHAT ARE THE BARRIERS THAT HAVE A REASONABLE CHANCE OF GETTING CONSENSUS AROUND? AND WHAT ARE THE BARRIERS THAT LEND THEMSELVES WELL TO MOBILIZATION OF THAT KIND OF POWER? SO, WE NEED YOUR HELP. YOU'RE THE EXPERTS. WE ARE NOT GOING TO GET TOO MANY OPPORTUNITIES TO ASK YOU WHAT YOU THINK THE ADVOCACY COMMUNITY SHOULD DO. WE NEED YOUR HELP A LITTLE BIT IN PRIORITIZING SOME OF THESE THINGS TO UNDERSTAND WHAT ARE THE BIGGEST BANGS FOR THE BUCK. WE WANT TO BE AT THE HEAD OF THE DOMINO BOARD HERE AND IF YOU TIP SOMETHING OVER, WHETHER IT IS A NEW BIOPSY POLICY OR SOMETHING ELSE, THOSE ARE SOME BIG ONES THAT WE CAN CHANGE AND MAKE A BIG DIFFERENCE. END OF SPEECH. SORRY ABOUT THAT. >> SO, YOU ALWAYS FRAME IT AND I THINK YOU CUT TO THE CHASE. AND I APPRECIATE THAT. ON THE ONE HAND, YOU DON'T WANT TO GET TOO GRANULAR AND SUPPOSE OR PRESUPPOSE THAT 3 OR 4 OF US AROUND THE TABLE CAN COME UP WITH THE RIGHT ANSWER. BUT, AT THE END OF THE DAY T IS A MATTER OF, I THINK, PRIMING THE PUMP. AND NOT MORE MINIMIZE THE OTHER BARRIERS AND ISSUES AND NEVER TO TAKE AWAY FROM OTHER IMPORTANT AREAS OF RESEARCH, BUT THE NCI LAUNCHING AN INITIATIVE THAT CHANGES THE LANDSCAPE OF DEVELOPMENT OF TARGETED AGENTS FOR CHILDHOOD CANCER. HOWEVER THAT IS FORMULATED. AS OPPOSED TO REPACKAGING. WE HAVE VERY IMPORTANT PROGRAMS. YOU HEARD ABOUT THEM. NO ONE WANTS TO TAKE AWAY THOSE PROGRAMS. BUT, MANY OF THOSE PROGRAMS DATE BACK 10 YEARS. NOTHING WRONG WITH THEM, BUT WE NEED NEW INITIATIVES AND NEW RESOURCES AND ULTIMATELY, IT COMES FROM THE NCI I THINK TO CONSIDER THAT, BUT IN THE CURRENT ECONOMIC CLIMATE IS HOW DO YOU GROW A PROGRAM IN THE CURRENT ECONOMIC CLIMATE? IF UP TO ASK ME WHAT WOULD TAKE AWAY THE GREATEST BARRIERS? IS LAUNCHING A MAJOR NEW INITIATIVE AND BRINGING TARGETED THERAPY TO CHILDHOOD CANCERS IN WHATEVER FORMAT THAT COULD ROLLOUT WHICH WOULD RANGE FROM DISCOVERY TO SCREENING, TO IMPLEMENTATION. >> AND I WOULD JUST ECHO YOUR SUGGESTION. BUT AUGMENT IT THAT THIS NEW PROGRAM REALLY BE NOT JUST A PUBLICLY-FUNDED PROGRAM, BUT A PUBLIC-PRIVATE FUNDED SPONSORED-SUPPORTED PROGRAM. AND I THINK THE INITIATIVE WITH THE MASTER PROTOCOLS, COULD CERTAINLY BE USED AS AN EXAMPLE. AND AS AN EXAMPLE, IT IS BEING DONE. WHY FOR SQUAMOUS CELL NONSMALL CELL LUNG CANCER AND WHY NOT FOR NEUROBLASTOMA OR WHY NOT FOR RELAPSE ACUTE [ INDISCERNIBLE ] I REALLY THINK THAT THAT IS AN AREA THAT COULD BE PACKAGED, SUPPORTED, AND ADVOCATED FOR VERY HEAVILY. >> I MEAN, TO PUT IT -- [ INDISCERNIBLE ] SO DAVID, I AGREE, WHAT YOU FRAMED IS EXACTLY WHAT YOU NEED AND I DON'T KNOW WHETHER THERE OUGHT TO BE A SORT OF ONE-DAY OR TWO-DAY WHERE THE LEADERS ACROSS THE FIELD IN ADVOCACY AND PEDIATRIC CANCER COME UP AND AT THE END OF THE TWO DAYS THIS IS OUR AGENDA. THIS IS OUR AGREED UPON AGENDA. I THINK IT IS REALLY IMPORTANT. AND WE ALL GET A LITTLE NERVOUS BECAUSE THERE ARE A LOT OF THINGS TO DO. BUT AT THE END OF THE DAY, IT IS CHANGING THE WAY WE ARE DOING THINGS IN A WAY THAT IS TAKING ADVANTAGE OF THE OPPORTUNITIES THAT, FOR WHATEVER REASON, WE DON'T HAVE THE FUNDS, WE DON'T HAVE THIS OR THE PROTOCOLS OR FDA APPROVAL OR -- IT'S ALL OF US TOGETHER. BUT JUST TO GIVE YOU A VERY CONCRETE SPECIFIC EXAMPLE. SOMETHING AGAIN IS NEAR AND DEAR TO MY HEART BECAUSE I HAVE BEEN INVOLVED IN THIS IS THE PARP-INHIBITOR WITH TAM ZOL MIDE WHICH YOU HEARD DISCUSSED. THE HISTORY OF THIS IS THAT PARP INHIBITORS HAVE BEEN PROVE TO BE VERY EFFECTIVE IN BRCA MUTANT BREAST CANCER, BRACKRA 2, BECAUSE THAT'S A DNA REPAIRED DEFECT SO THEY BECOME TOTALLY RELIANT ON THE DNA REPAIR THAT THE PARP-INHIBITOR BLOCKS. SO IT WAS AN OBVIOUS THING AND IT IS LOOKING VERY PROMISING. IT SHOWED UP IN EWING SARCOMA BECAUSE A GROUP AT THE SANGER INSTITUTE DID A BROAD SCREEN OF 3000 CELL LINES AND EVERY KNOWN DRUG. AND THEY FOUND, YOU KNOW, THE PROOF OF PRINCIPLE, FOUND THAT MELANOMA CELLS RESPONDED TO B RAV INHIBITOR AND CML CELLS RESPONDED TO AMAT EN. THE MOST UNEXPECTED FINDING WAS THAT EWING SARCOMA CELLS RESPONDED TO A PARP-INHIBITOR. WE STILL DON'T KNOW WHY THAT IS. BUT IT IS TRUE. SO NOW THERE ARE GOING TO BE STUDIES DONE. AND MY FEAR IS, AND I GUARANTEE YOU THERE WILL BE RESPONDERS AND NONRESPONDERS. AND WE BETTER DO THE STUDY WHERE WE GET IT RIGHT AND KNOW AFTER THAT STUDY WHO WE NEED TO SELECT, AND THOSE PEOPLE THAT WILL RESPOND. AND CO GLUM SAY, WE ONLY HAVE 4000 DOLLARS PER PATIENT AND WE CAN'T AFFORD TO DO THE STUDY. AND THEY MAY SAY, WE CAN GIVE YOU A LITTLE BIT OF MONEY BUT WE ARE PUTTING OUR MONEY IN GETTING TO TO BREAST CANCER PATIENTS BECAUSE THAT'S WHERE THE MONEY IS. THAT IS WHAT WE ARE NOT DOING. AND WE HAVE GOT TO FIGURE OUT WAY WAY TO DO IT BECAUSE THIS IS IMPORTANT. >> I DO AGREE. I POINT OUT THE NCI IS FUNDING BIOPSIES ON HOW MANY THOUSANDS OF ADULT PATIENTS FOR THIS? >> I HAVE NO IDEA. >> IT'S THOUSANDS. THAT'S THE RIGHT THING TO DO. BUT THEY ARE PAYING FOR IT. >> WELL, BUT YOU KNOW, I CAN TELL YOU IN THE COG DISCUSSION THERE WILL BE PEOPLE THAT WILL GET UP AND ARGUE AND SAY WE CAN'T DO BIOPSIES. >> WE'LL MANAGE THOSE THREE PEOPLE. >> AND YOU NEED FAR LESS -- >> AND IF WE COULD FRAME IT IN A BROADER, NOT JUST FOCUS ON ONE STUDY, BUT HERE IS HOW WE HAVE TO DO THESE STUDIES AND HERE IS WHAT WE NEED TO DO THEM AND YOU COULD HELP DO THAT. I DO THINK WE NEED TO COME UP WITH 3-4 PRINCIPLES HERE AND YOU KNOW, WHAT YOU SAID IS EXACTLY RIGHT. >> SO I HEARD A LOT TODAY ABOUT THE ECONOMIC DRIVERS FOR THE RESEARCH AND THE PERCENT THAT IS CONTRIBUTED BY THE DIFFERENT KEY PLAYERS THAT IS USUALLY ADVOCACY, INDUSTRY AND GOVERNMENT SECTORS. WHAT I HAVEN'T HEARD FOLKS DISCUSS IS SOMETHING USUAL I DISCUSSED IN PEDIATRIC CONTEXT IS COVERAGE. COVERAGE FOR INDICATIONS IS USUALLY MUCH MORE LIMITED AND THAT IS THE MAJOR REASON, ASIDE FROM THE NUMBERINGS OF PATIENTS, ALSO BEING SMALLER, THAT INDUSTRY DOESN'T SEEM TO GO INTO PEDIATRIC INDICATIONS. IS THAT THE CASE IN THE PEDIATRIC CANCER SPACE? >> NO. I MEAN, I DON'T THINK THAT IS THE CASE. BECAUSE RESEARCH IS SO INTEGRATED WITH CLINICAL CARE, AND CLINICAL CARE IS ALMOST EXCLUSIVELY AT ACADEMIC CENTERS, I'M NOT SAYING COVERAGE IS EASY BUT I DON'T THINK COVERAGE HAS BEEN A LIMITATION. NOW WITH THAT SAID, I THINK THAT YOU MOVE INTO SURVIVORSHIP AND THERE ARE PROBABLY PEOPLE WHO ARE MUCH MORE KNOWLEDGEABLE THAN YOU OR I ON THAT. FOR NEWLY DIAGNOSED CHILDREN, GENERALLY, THAT HAS NOT BEEN A LIMITATION. INDUSTRY'S LACK OF INVOLVEMENT IS NOT INSURANCE ISSUE. IT'S HOW DO WE DEVELOP A DRUG FOR 300 PATIENTS A YEAR? NO THANK YOU. [ LOW AUDIO ] >> IT REALLY ISN'T AN ISSUE. VIRTUALLY 90% OF THE THERAPY WE USE FOR PEDIATRIC CANCER GETS USED OFF LATIAL. SO, EVEN FOR THAT OFF LABEL USE, AND CLINICAL TRIALS ENROLLMENT FOR SOME REASON, FORTUNATELY, COVERAGE REALLY HASN'T BEEN A HUGE ISSUE. FROM TIME TO TIME THERE ARE AND IN CERTAIN GEOGRAPHIC AREAS, BUT OVERALL -- >> SO, 20 YEARS AGO, THE COST OF THAT DRUG WAS REASONABLE. THAT IS NO LONGER THE CASE WHEN A DRUG IS APPROVED FOR AN ADULT INDICATION, WE HAVE TO HAVE A SUPPLIER OF THAT DRUG BECAUSE WE ARE NOT GOING TO GET THAT -- NOT GOING TO PASS THAT COST THROUGH DURING A STUDY BECAUSE THE COST OF THESE DRUGS AS EVERYONE KNOWS IS GENERALLY EXTRAORDINARILY HIGH. SO THE LANDSCAPE HAS CHANGED FROM THE STANDPOINT OF IT'S BECOMING MORE DIFFICULT FOR US TO STUDY DRUGS THAT ARE APPROVED FOR ADULT INDICATIONS BECAUSE OF THE COST OF THOSE DRUGS. >> TAKE CONTROL A LITTLE BIT OF SCHEDULE AGAIN. WE HAVE FALLEN A HALF HOUR BACK. I APPRECIATE ALL THE COMMENTS AND IT'S BEEN USEFUL BUT THE NEXT SECTION IS WHERE WE HAVE THE ADVOCATES TALK TO US ABOUT EXPERIENCES AND THOUGHTS AND I DON'T WANT TO SHORT CHANGE THAT. SO WE ARE GOING TO ELIMINATE THE WORKING GROUP DISCUSSION AT THE END OF THE AGENDA AND TAKE THAT HALF HOUR OUT WHICH ACCOMMODATES FOR WHAT WE JUST WENT THROUGH. ONE OF THE HEADS OF THE WORKING GROUPS IS GOING, THANK GOD! I'M THE HEAD OF THE OTHER WORKING GROUP AND I'M SAYING THE SAME THING. [ LAUGHS ] OY SAW YOU FRANTICALLY TYPING JUST A MINUTE AGO. BUT WHAT I'D LIKE TO DO IS TO MOVE US INTO THIS SECTION CALLED, ADVANCING PEDIATRIC CANCER RESEARCH THROUGH ADVOCACY, WHICH GIVES US A CHANCE TO HEAR FROM A NUMBER OF THE ADVOCACY GROUPS THAT ARE HERE ABOUT THEIR EXPERIENCES AND THOUGHTS AND WE'LL MOVE FROM THAT AS THE LAST MODULE OF THE DAY INTO NEXT STEPS. THANK YOU VERY MUCH FOR THAT LAST REALLY GOOD SESSION. LISA, WOULD YOU LIKE TO BE FIRST UP? A TICH TICH WILL BE OUR FIRST SPEAKER -- LEASE TICHENOR FROM QUADW WILL BE OUR FIRST SPEAKER. >> THANK YOU VERY MUCH FOR HAVING ME HERE TODAY. THIS IS MY SON, WILLIE. WHEN HE WAS 16, WE LEARNED THAT HE HAD OSTEOSARCOMA. THREE YEARS LATER, HE DIED. I SAY THESE THINGS ABOUT WILLIE THAT ALL OF US SAY ABOUT THE KIDS WE LOST. HE WAS BRIGHT, SUNNY, TALENTED, HE WAS A BIGHEARTED HANDSOME BOY THAT LOVED HIS MAMA. DURING HIS TREATMENT, THERE WAS HARDLY A MOMENT WHEN HE WASN'T IN SOME KIND OF CRISIS. IT'S A HORRIFIC THING TO GO THROUGH EVEN IF YOU LIVE. MY HUSBAND, MACK AND I, HAD THE EXPERIENCE OF WATCHING OUR CHILD DIE. WILLIE HAD A REMARKABLE PIECE ABOUT KNOWINGNESS AND HE HAD A CONVERSATION WITH US BEFORE HE DIED IN WHICH HE ASKED US TO HELP HIS FRIENDS AND TO SEE IF WE COULD SEEK ADDITIONAL TREATMENTS FOR PATIENTS LIKE HIMSELF. IT WAS AN INCREDIBLE GIFT HE GAVE US. FROM THIS CONVERSATION, OUR FAMILY CREATED THE QUADW FOUNDATION. IT STANDS FOR WHAT WOULD WILLIE WANT. IT WAS NATURAL THAT WE INVOLVED HIS FRIENDS IN THE LEADERSHIP OF THE ORGANIZATION. OUR BOARD OF DIRECTORS IS EIGHT FRIENDS THAT WALKED WITH HIM THROUGH HIS ILLNESS. THEY WERE EAGER TO MAKE A DIFFERENCE IN SOMETHING THAT HAD A PROFOUND IMPACT ON THEIR LIVES. FROM THE OUTSET, THEIR MISSION HAS BEEN TO SUPPORT FINDING NEW AND BETTER TREATMENT OPTIONS FOR OUR PEOPLE LIKE THEIR FRIEND. THE BOARD DECIDED ON A SPECIFIC GOAL FOR SARCOMA RESEARCH. SO NOW I'M GOING TO TELL YOU A STORY ABOUT HOW WE SET OUT TO ACHIEVE THAT GOAL. WE HAVE THREE PRINCIPLES THAT WE BELIEVE IN IN OUR WORK IN QUADW. THE FIRST IS COLLABORATION. YOU WILL SEE HOW THESE PLAY OUT AS WE MOVE THROUGH THE CASE STUDY. AFTER WILLIE DIED WE DIDN'T KNOW WHAT TO DO. THROUGH THE KINDNESS OF WONDERFUL DOCTORS WE GOT CONNECTED WITH THE AACR. THEY SPONSORED A PANEL OF SARCOMA EXPERTS LED BY LEE HELMAN. I THINK THEY WERE SURPRISED TO WALK INTO A ROOM FULL OF 19 AND 20-YEAR-OLDS. AND WE WANT THEM TO BE EFFICIENT AND LEVERAGABLE. AND THE CONVERSATION AROUND THE EXPERT PANEL TABLE THAT DAY REPRESENTED THAT AT ITS BEST. THE GROUP FOCUSED ON THE LARGER PROBLEM OF LACK OF TREATMENT OR LACK OF PROGRESS AND TREATMENTS FOR SARCOMA PATIENTS AND JUST AS THEY'RE SURPRISED ABOUT WHO WE WERE, WE WERE REALLY SURPRISED AT WHAT WAS IMPEDING PROCESS IN THE FIELD. THEY IDENTIFIED SEVERAL ROAD BLOCKS AND SUGGESTED A COLLABORATION WITH THE CHILDREN'S ONCOLOGY GROUP AS A POTENTIAL WAY FOR QUADW TO WORK. THE COD HAD AN OSTEOSARCOMA TISSUE BANK OF UNKNOWN QUALITY LABBING IN CLINICAL ANNOTATION, AND THERE WAS A BACKLOG OF REPORTS WAITING FOR STATISTICAL ANALYSIS. FROM THAT, THE QUADW CHILDHOOD SARCOMA BIOSTATISTICS AND ANNOTATION OFFICE WAS CREATED. WE HAVE YET TO CREATE A CATCHY ACKANISM BUT WITH QUADOF THE SUPPORT, THE OSTEOSARCOMA TISSUES ARE NOW 90% ANNOTATED AND WE HAVE A BIOSTATISTICIAN WHO WORKS FULL-TIME ON THE PROJECT IN THE OFFICE. WE ARE VERY PLEASED WITH THE ACCOMPLISHMENTS THAT HAVE OCCURRED IN THE YEARS WE HAVE WORKED WITH COG AND FEEL LIKE IT IS DUE TO THE VERY HIGH QUALITY OF LEADERSHIP AND BESIDES THE SCORECARD YOU JUST SAW, THERE HAVE BEEN ADDITIONAL ACHIEVEMENTS WE FEEL ARE VERY IMPORTANT TO MAKING PROGRESS IN TREATMENT AND DRUG DEVELOPMENT. THE THIRD PRINCIPLE IS WHAT WE CALL LIGHT HEARTED AND WHOLE HEARTED. WILLY AND HIS FRIENDS EXPERIENCED A LOT OF LAUGHTER AND JOY WITH EACH OTHER DURING DIFFICULT TIMES. QUADS A UNIQUE COLLECTION OF CHARACTERS. AND I THINK THE GROUP FROM COD WILL TELL YOU THEY HAD A FEW GOOD LAUGHS WHILE WORKING ON THIS PROJECT AND MAKE SHOULD GO SIGNIFICANT ACCOMPLISHMENTS. QUADW BOARD ENERGIZED ABOUT THE SUCCESS OF THE COG PROJECT BUT THEY LEARNED HOW MUCH MORE THERE IS TO DO. THEY QUOTE A PHRASE USED BY WILLIE, THAT IS PRETTY GOOD BUT WE CAN DO BETTER. SO ONE OF THE PLACES THEY FEEL LIKE THEY CAN DO BETTER IS IN FUNDRAISING TO INCREASE OUR CAPACITY FOR GIVING. THE YEAR WILLWENT TO COLLEGE, HIS GIRLFRIEND ASKED THEM TO MAKE A LIST OF THINGS THAT MADE HIM FEEL ALIVE. WE FOUND THIS LIST ON HIS COMPUTER AFTER HE DIED. IT HELPS US TO UNDERSTAND THAT WE ARE DOING WHAT WILLIE WANTED AND IN A WAY THAT HE WOULD HAVE WANTED. NUMBER 23 WAS LEARNING STUFF AND FEELING SMART, THAT WAS HIS WORDS, NOT OURS. THE QUADW BOARD IS CONSTANTLY TRYING TO LEARN MORE ABOUT THE FIELD IN WHICH WE ARE WORKING. BEING OUTSIDE WHEN IT'S NICE. WE FEEL LIKE IF WE DON'T GIVE UP, SOMEBODY WILL HAVE A BETTER DAY. MY FRIEND, WILLIE'S FRIENDS WERE SO IMPORTANT TO HIM. AND THEY REALLY WANT TO MAKE A DIFFERENCE AND THEY ARE GOING TO BE AROUND FOR A LONG TIME. LAUGHING. WE DECIDED IMMEDIATELY THAT THIS WAS GOING TO BE HARD TO DO UNLESS WE HAD LAUGHS ALONG THE WAY. AND SO WE DO. SO NOW YOU THAN RELATIONSHIPS ARE REALLY IMPORTANT TO WILLIE. IT'S CLEAR THIS MAP OF QUADW RELATIONSHIPS THAT WE CAN REALLY BEST DESCRIBE OUR WORK. AND AS I SAID IN THE BEGINNING, OUR BOTTOM LINE GOAL NEW TREATMENTS, BETTER TREATMENTS FOR PATIENTS LIKE WILLIE. WE ARE CONVINCED THAT SUPPORTING THE INFRASTRUCTURE IS THE MOST EFFECTIVE WAY TO FILL THE PIPELINE FOR NEW TREATMENT IDEAS. BUT, OUR RELATIONSHIPS HAVE ALSO BEEN KEY IN OUR QUEST TO BRING INVESTIGATIONAL TREATMENTS TO THE CLINICAL TRIAL STAGE. I THINK WILLIE WOULD BE PROUD OF HIS FRIENDS. THANK YOU. [ APPLAUSE ] >> THANK YOU VERY MUCH. WHY DON'T WE GO THROUGH THE GROUPS AND THEN WE CAN COME BACK AND ASK QUESTIONS OF THINGS THAT WE FIND PROVOCATIVE AND INTERESTING. TING WILL BE NICE TO GET FEEDBACK. MAUREEN? >> [ OFF MIC ] >> I'M A LITTLE DIZZY. [ LAUGHS ] >> THANK YOU FOR THIS OPPORTUNITY. MY NAME IS MAUREEN LILLY. I'M THE EXECUTIVE DIRECTOR OF CHILDREN'S CLOUD FOR CANCER ADVOCACY. WE HAVE WORKED FOR 15 YEARS AN AN INDEPENDENT NATIONAL CHAMPION FOR CHILDREN WITH CANCER, FAMILIES AND THE SURVIVORS. WE HAVE DONE IT THROUGH WORK TO ACHIEVE MORE RAPID ACCESS TO LESS TOXIC AND MORE EFFECTIVE PEDIATRIC CANCER THERAPIES, TO EXPAND RESOURCES FOR CHILDHOOD CANCER RESEARCH AND CARE AND TO DESTINIES AND CHALLENGES OF CHILDHOOD CANCER SURVIVORS. YOU HEARD LISA TALK ABOUT THEIR APPROACH. OUR APPROACH HAS BEEN THROUGH NATIONAL DEBATE AND PUBLIC POLICY AND LEGISLATION. AND DOING IT IN A VERY THOUGHTFUL AND ANALYTICAL WAY. WE ARE PLEASED TO HAVE DISCUSSION TODAY TOGETHER ALIGNING THE ROLES OF THE ADVOCACIY COMMUNITY AND THE RESEARCH COMMUNITY. AND THE ISSUE OF REDUCING BARRIERS PEDIATRIC ONCOLOGY, DRUG DEVELOPMENT HAS BEEN A PRIORITY FOR CHILDREN'S CLOUD SINCE IT BEGAN IN 1999. AND I'D LIKE TO THANK DR. LEHMANN FOR GETTING THROUGH THE ALPHABET SOUP OF RECENT LEGISLATION. THESE ARE ALL IMPORTANT PIECES INDIVIDUALLY AND TOGETHER. AND IN RECEIPT YEARS, WE FOCUSED ON HOW TO EFFECT THE POLICY CHANGES DURING THE PDUFA REAUTHORIZATION. DURING CONSIDERATION OF FDASIA, WE ADVOCATED ALONG WITH OTHER ORGANIZATIONS LIKE AMERICAN ECONOMY OF PEDIATRICS, TO PERMANENTLY AUTHORIZATION OF THE BPCA AND PRE TOO. ENSURE THESE PROGRAMS DID REMAIN INTACT AND DIDN'T HAVE TO COME UP FOR AUTHORIZATION EVERY 5 YEARS. WE ALSO ADVOCATEDDED FOR AND CONTINUE TO ADVOCATE FOR CERTAIN CHANGES TO PREA TO MAKE IT WORK MORE EFFECTIVELY FOR CHILDREN WITH CANCER. IT IS CRITICAL THE LANGUAGE OF PREA BE CHANGED SO CHILDREN CAN HAVE ACCESS TO MODERN APPROACHES TO CANCER THERAPY. CURRENTLY PREA REQUIRES THE SPECIFIC CANCER THAT OCCURS IN ADULTS DETERMINES WHAT PEDIATRIC STUDIES CAN BE REQUIRED FOR THOSE AGENTS. BECAUSE CANCERS DON'T ESSENTIALLY OCCUR IN CHILDREN, BREAST CANCER, COLON, CANCER, PROSTATE CANCER, THAT MEANS THAT THERE IS A WAIVER ISSUED AND TRIALS ARE NOT REQUIRED. AS YOU HEARD TODAY, AND SOME TERRIFIC PRESENTATIONS THIS MORNING, THERE ARE OPPORTUNITIES THAT WE ARE MISSING. SCIENTIFIC ADDNESS ADVANCES IDENTIFIED KEY PATHWAYS FOR MANY KANSAS WHICH DEPEND ON THE SPECIFIC MOLECULAR CHARACTERISTIC OF THOSE TUMORS. IT CAN BE USED TO ADVANCE CHILDHOOD CANCER DRUG DEVELOPMENT, TRIALS SHOULD BE BASED ON THOSE DEVELOPMENTS OF DRUGS THAT ARE BASED ON THE PATHWAYS AND THE OPPORTUNITIES BETWEEN THE ADULT CANCERS AND THE CHILDHOOD CANCERS NOT ON LOCATION OF THOSE CANCERS. THIS IS SOMETHING WE ARE ADVOCATING FOR. AND ALSO, BECAUSE ALL CHILDHOOD CANCERS ARE CLASSIFIED AS ORPHAN DISEASES TO EFFECTIVELY CHANGE THE DRUG DEVELOPMENT, THE CURRENT ORPHAN DRUG DEVELOPMENT FOR CHILD HAD CANCER NEEDS TO BE ELIMINATED - AUTO EXCLUSION. THE OTHER AREA WE HEARD ABOUT IS THE CHALLENGES ON THE RESEARCH SIDE. THE LACK OF GENETIC INFORMATION. DR. SMITH TALKED ABOUT THE -- I WAS SO RELIEVED TO HEAR A REFLECTION OF THE NEED IN SUCH A BROAD AREA. ANOTHER DRUG DEVELOPMENT IS THROUGH A DEEPER UNDERSTANDING OF THE MOLECULAR AREAS IN CHILDHOOD CANCER WORKING TO IMPROVE THE BASE OF KNOWLEDGE ABOUT CHILDHOOD CANCER BY PROMOTING LEGISLATION. THE CPW REAUTHORIZATION ACT IS CURRENTLY BEFORE CONGRESS AND WE INTRODUCED THE HOUSE AND SENATE ABOUT NINE MONTHS AGO AND IT HAS BIPARTISAN SUPPORT AND IT HAS -- I DON'T KNOW THE CURRENT NUMBER OF SPONSORS BUT IN THE NEIGHBORHOOD OF 40 COSPONSORS T IS ACTIVELY BEING SUPPORTED AND BEING PUSHED FORWARD. ONE OF THE THINGS THAT IT WOULD DO, THE MOST IMPORTANT THING FOR THE PURPOSES OF THIS DISCUSSION, IT WOULD REMOVE THE BARRIERS TO IMPROVE COLLECTION OF BIOSPECIMENS AND AUTHORIZE RESOURCES FOR THE NCI TO DO SO. SO THE CURRENTLY BIOSPECIMENS CAN ONLY BE COLLECTED FOR APPROXIMATELY HALF OF THE CHILDREN DIAGNOSED WITH CANCER IN THE UNITED STATES YOU WOULD RESULTING IN LIMITED OPPORTUNITIES FOR SCIENTISTS AND MEDICAL PROFESSIONALS TO INVESTIGATE THESE DISEASES. THERE ARE EFFORTS UNDERWAY TO IMPROVE THIS AS YOU HEARD FROM PRIVATE FUNDERS. BUT THIS LEGISLATION WOULD CENTRALLY COORDINATE THOSE EFFORTS. IT WOULD MAKE THE SPECIMENS ASSOCIATED DATA MORE ACCESSIBLE TO RESEARCHERS AND EARLIER POINTS. AND ENABLE COLLECTION FROM CHILDREN WHO AREN'T CURRENTLY ENROLLED IN NCI-SPONSORED TREATMENT RESEARCH TO ALSO HAVE THEIR INFORMATION INCLUDED IN THE CENTRAL DATABASE. WITH CONSENT ISSUES. GIVEN LIMITED RESOURCES AND STAGNANT CONGRESS, IT IS IMPORTANT FOR US TO WORK TOGETHER TO ADVANCE THESE LEGISLATIVE EFFORTS BY PUTTING WEIGHT OF COMMUNITY, PARENTS, ADVOCATES, FAMILIES, SURVIVORS, PROVIDERS, BEHIND THE PRIORITIES. DAVID MEANED TO YOU THE ALLIANCE OF CHILDHOOD CANCER. THIS IS A ORGANIZATION THAT HAS BEEN AROUND FOR ABOUT 13 YEARS. IT'S A COLLECTION OF NOW 28 ORGANIZATIONS, INCLUDING BOTH THE CHILDHOOD CANCER NATIONAL ADVOCATE ORGANIZATIONS AND THE PROFESSIONAL SOCIETIES. WE ARE ALL AT THE TABLE TALKING ABOUT THE POLICIES THAT MIGHT WORK TO PROVIDE MORE OPPORTUNITIES FOR THE NEXT DEVELOPMENT OPPORTUNITIES. I'M HONORED TO BE CO-CHAIR OF THAT GROUP CURRENT LIE. THERE IS ALSO THE GROUP YOU'LL HEAR FROM TODAY FROM THE NEWLY-FORMED CAP 2. THESE ARE COALITIONS FROM MANY ENTITIES AND THE ADVOCATES COMMUNITY HAS TO WORK TOGETHER AND WE ARE DOING SO. ADVOCATES NEED TO BE BETTER EQUIPPED TO MAKE THE CASE. BEFORE LEGISLATION AND MEMBERS OF THE CONGRESS AND SENATORS IN THEIR HOME DISTRICTS. THEY HAVE POWERFUL STORIES TO TELL. AND AS YOU HEARD NANCY TALK ABOUT HER PRESENTATION. THE SAME IS TRUE WHEN WE GO TO CAPITOL HILL AND TALK TO THOSE. YOU CAN MAKE A DIFFERENCE IN TRYING TO GET LEGISLATION PASSED. WE MUST USE OUR RESOURCES THROUGH WORKSHOPS, MEETINGS, AND REQUESTS FOR PERMITS FROM FDA. LIKE THE MEETING HELD IN JANUARY, IT'S AN IMPORTANT OPPORTUNITY FOR ADVOCATES. WE NEED TO EXPRESS OUR SUGGESTIONS FOR THE STRATEGIC PLAN BEING DEVELOPED NOW REGARDING BARRIERS TO DRUG DEVELOPMENT FOR PEDIATRIC CANCERS. TOGETHER, WE MIGHT URGE THE FD TOO. PUT FORWARD IN THE STRATEGIC PLAN THE NEED IF MECHANISMS BY WHICH WE CAN PRIORITIZE STUDIES AND ASSURE THAT PEDIATRIC STUDIES ARE BEING COORDINATED FOR NEW AGENTS BASED UPON THEIR TARGETED PATHWAYS AND ADULT CANCERS. FINALLY, I WANT YOU TO REMEMBER REBECCA LILI. OUR DAUGHTER WAS DIAGNOSED IN 1991. THAT'S A LONG TIME AGO. SHE HAD AN AGGRESSIVE BRAIN TUMOR. GLIOBLASTOMA. AND THAT THING JUST ROLLS OFF MY LIPS NOW AND WOULDN'T HAVE BACK THEN. WE ARE HONORED TO PARTNER WITH HER JOURNEY FOR SIX YEARS WITH CANCER AND BRAIN TUMORS. SHE DIED 17 YEARS AGO IN 1997. I WAS PUTTING TOGETHER MY INFORMATION FOR THIS TALK TODAY. I WANTED TO CELEBRATE THE THINGS THAT HAD BEEN DONE AND STRIDES THAT HAVE BEEN MADE BUT ALSO NOT LOSE SIGHT OF THE AFFECT THAT SOME CANCERS FOR CHILDREN WHERE THERE ARE HAVE BEEN NO STRIDES. FOR REBECCA THERE HAS BEEN NO IMPROVEMENT IN 30 YEARS OF THAT PARTICULAR BRAIN TUMOR. THE SAME THING CAN BE SAID FOR SEVERAL OTHER CHILDHOOD CANCERS. THERE IS A LOT OF WORK THAT STILL NEEDS TO BE DONE. I THINK WE CAN DO BETTER. I AM REALLY THRILLED THERE ARE A LOT OF SMART PEOPLE IN THIS ROOM AND I REALLY HOPE THAT YOU INDIVIDUALLY AND COLLECTIVELY CONSIDER THE NEEDS OF OUR CHILDREN. THANK YOU. [ APPLAUSE ] >> NEXT WE'LL HEAR FROM RUTH HOFFMAN. >> I WANT TO THANK YOU FOR HAVING FOCUSED TODAY ON PEDIATRIC CANCER. WE OFTEN HEAR THAT CANCER, THE ANALOGY, CANCER IS LIKE FIGHTING A BATTLE AND WINNING THE WAR. WE ARE SOLDIERS FIGHTING THE WAR. WIN THE BATTLE, LOSE THE BATTLE. THAT ANALOGY IS USED ALL THE TIME FOR FIGHTING CANCER. AND I WANTED TO INITIALLY REMIND US THAT IN THIS BATTLE, WITH CHILDHOOD CANCER, IT'S THE LITTLE CHILDREN THAT ARE THE SOLDIERS AND WE ARE THE SECRETARY OF DEFENSE, AND MAYBE OUT TO THE ACTUAL COMMANDER-IN-CHIEF AND WE HAVE AN OBLIGATION AND I'M CHARGING TO YOU TAKE YOUR INTELLIGENCE TODAY TO ARM THESE KIDS WITH TOOLS AND WITH EQUIPMENT AND WEAPONS FOR THIS BATTLE AND I THINK IT IS REALLY IMPORTANT. JUST AGAIN TO COMPARE, IN OUR MILITARY, A LOT OF MONEY IS INVESTED AND OUR GOVERNMENT OBVIOUSLY IS VERY, VERY IMPORTANT AND SO IT SHOULD BE. DEVELOPED IN THE LAST FEW YEARS IS AN M200 LONG-RANGE SNIPER RIFLE CAPABLE OF HITTING A TARGET FROM 1.5 MILES. CLEAR SHOT STATE-OF-THE-ART WEAPON TO ALLOW SOLDIERS TO TARGET WEAPONS. WE ARE STILL TREATING OUR CHILDREN WITH WEAPONS THAT ARE ANNUAL WAITED. LIKE GIVING OUR SOLDIERS -- APTED WAITED -- LIKE GIVING THEM BOLT ACTION RIFLES AND EXPECTING THEM TO WIN THE WAR. WE CANNOT WIN IF WE DON'T GIVE OUR CHILDREN THE WEAPONS TO DO THAT. SO I'M GOING TO GIVE A FACE TO THIS DISEASE. THIS IS MY DAUGHTER, DIAGNOSED IN 1987. WE HAVE BEEN AT THIS FOR 27 YEARS. DIAGNOSED WITH LEUKEMIA AT AGE 7 AND ONE OF THE FIRST GENERATION SURVIVORS OF BONE MARROW TRANSPLANTATION. BUT THE DRUGS SHE HAD, AND WHEN THEY WERE 50 SET ASIDE. -- WHEN THEY WERE FIRST SET ASIDE. SO THESE ARE THREE ESSENTIAL CONDITIONING INDUCTION CHEMOTHERAPIES. AND I'LL SHOW YOU IN A FEW MINUTES THOSE THREE DRUGS ARE STILL STANDARD OF CARE FOR AML. THEY WERE SYNTHESIZED IN THE 1950s. TRANSPLANT CONDITIONING: [ READING ] IT WAS BECAUSE I WAS PREGNANT WITH TWINS SO THEY HAD TO DELAY TO KEEP HER UNDER MAINTENANCE FROM GOING INTO RELAPSE AND SHE HAD 1600 ROUNDS OF RAIDITATION HER BODY. BUT UNLIKE ALL THE FAMILIES AND CHILDREN IN THIS THAT SPOKE TODAY, MY DAUGHTER DID SURVIVE BUT SHE LIVED INCREDIBLE. SHE HAD TOXICITY, LUNG DAMAGE, TERRIBLY HIGH BLOOD PRESSURE, WHICH LEADS TO A LOT OF PROBLEMS FOR HER. SHE HAD CATARACTS IN BOTH EYES, ENDOCRINE DYSFUNCTION, GROWTH ISSUES, SHE HAD AY SECONDARY TEAR DUCT THAT TREATED WITH RADIATION AND THAT TOOK AWAY HER SALIVA IN HER MOUTH AND TEAR DUCTS. WE WERE TOLD SHE WOULD BE IN FIRSTILE AND SHE GROUP UP LIVING THAT WAY. SHE WAS MARRIED IN 2006 AND WHAT WE DIDN'T KNOW WAS IN 2008, - APRIL FOOLS DAY SHE CALLED ME AND SHE WAS HAVING A ROUTINE PREGNANCY TEST TO CHECK TO SEE WHETHER HER SECONDARY CANCER HAD COME BACK. SHE HAD TO DO THAT EVERY 6 MONTHS AND CALLED ME AND SAID, MOM, I'M PREGNANT. AND IT'S LIKE -- THAT'S NOT REALLY FUNNY BECAUSE YOU'RE STERIL. AND SHE SAID, NO. I'M PREGNANT. SO I KNEW BEFORE HER HUSBAND DID. WHAT WE DIDN'T KNOW IS THAT THE TREATMENT THAT SHE HAD CAUSED INCOMPETENCY AND THAT HASN'T BEEN DOCUMENTED ANYWHERE. SHE WAS AT THAT POINT 12 WEEKS PREGNANT. AND WE DID KNOW THROUGH DOING SOME RESEARCH AT THAT POINT IN TIME THAT IT CAUSED UTERINE VASC LIN INSUFFICIENCY SO A LACK OF BLOOD SUPPLY TO THE UTERUS. THAT MEANT SHE WAS HOSPITALIZED IMMEDIATELY. WE HAD TO GET HER TO 24 WEEKS JUSTATION IN ORDER FOR THE BABY TO BE VIABLE. WHAT HAPPENED WAS NAOMI ACTUALLY WAS NOT ABLE TO GIVE ENOUGH BLOOD TO THE BABY. AND SHE ALSO DEVELOPED A VERY BAD INFECTION BECAUSE OF THE CERVICAL INCOMPETENCE IN NOT HAVING A CERVIX TO STOP INFECTION. SO AT 24 WEEKS SHE WAS INDUCED TO HAVE THIS BABY AND IT WAS BORN FOUR MONTHS EARLY AND WEIGHED ONE POINT 6 OUNCES AND 9.5 INCHES LONG. IF YOU LOOK AT YOUR PEN ON YOUR TABLE, SHE WAS JUST A LITTLE BIT LONGER THAN THAT. HER FEET, IF YOU CAN SEE HERE BETWEEN YOUR FINGERTIPS AND HER HANDS, AND TODAY HOPE IS A SEVERE EPILEPTIC. BUT MY GRANDDAUGHTER HAS SEVERE HEALTH ISSUES. SHE WAS IN THE NICU FOR 111 DAYS BEFORE SHE CAME HOME. AT THIS POINT, WHERE SHE IS BEING HELD HERE SHE WAS EIGHT WEEKS OLD. SO JUST TO GIVE YOU AN IDEA WHAT THAT WAS LIKE. THAT WAS THE FIRST TIME THAT NAOMI HELD HER. IF YOU LOOK AT THE HAND BY THE NECK, YOU CAN GET AGAIN PERSPECTIVE ON HOW SMALL SHE IS. HER LIFE TODAY AND THE SUFFERING SHE HAS SHE HAS GRAND MALL SEIZEIERS AND HER BRAIN SHUTS DOWN AND IT'S A 911 CALL EVERY TIME AND HER HEALTH ISSUES ARE A DIRECT RESULT OF THE TOXICITY THAT MY DAUGHTER RECEIVED FOR HER CANCER WHEN SHE WAS 7. AND MARLY WAS DIAGNOSED IN 2012 WITH ACUTE MY LOGICAL LEUKEMIA. THIS CHILD WE WORKED WITH THROUGH OUR ORGANIZATION. WE DO EXPENSIVE PATIENT NAV OFIGATION FOR FAMILIES. MARLY HAS MLL REARRANGEMENT. SHE ALSO RECEIVED HIGH DOSE CHEMOTHERAPY AND BONE MARROW TRANSPLANTED. THIS WAS MARLY'S DRUG. EXACTLY THE SAME. 27 YEARS LATER. [ READING ] AND AS A SIDE NOTE, DAUNORUBICIN IS ON THE BACKLOG LIST, DRUG SHORTAGE LIST. WHICH IS ANOTHER ISSUE OF AVAILABILITY OF DRUGS AND ACCESS TO CARE. MARLY ALSO HAD A LITTLE BIT OF A DIFFERENT CONDITIONING REGIMEN FOR TRANSPLANTATION. SHE HAD BUSULFAN. IT WASN'T A NEW DRUG. THEY PULLED OUT THE RAILEDDATION AND SHE RECEIVED THESE OTHER DRUGS AS WELL. SO THE CONCLUSION WITH EXCEPTION OF MY NOTES DOWN BELOW IS THERE IS NO NEW FDA APPROVED DRUGS TO TREAT PEDIATRIC AML SINCE MY DAUGHTER WAS DIAGNOSED IN 1987. WITH THE EXCEPTION OF THE ADULT DRUG APPROVAL. SO -- WAS APPROVED BY THE FDA - GREG QUOTE ME IF I'M WRONG BUT MY UNDERSTANDING, FOR ADULTS, AND THEN APPROVAL WAS WITHDRAWN AFTER A PHASE III STUDY IN ADULTS AND IT FAILED. I WAS ON THE IND WHEN IT WENT THROUGH MARKETING APPROVAL. IT WAS APPROVED FOR ALL. IT SEEMED A LITTLE BIT FOR AML AND MARLY DID GET A LITTLE BIT OF THAT AND WE DO HAVE TYROSINE KINASE INHIBITORS IN TRIAL RIGHT NOW. BUT NO FDA APPROVED DRUGS RANDOM. SO, ATCL, MOST OF YOU PROBABLY KNOW IS A CANCER FOUNDATION, AND WE ARE A NETWORK OF ORGANIZATIONS ACROSS THE COUNTRY IN 40 DIFFERENT STATES. AND I DON'T USUALLY PUT THIS UP THERE. MOST PEOPLE THINK OF THIS AS A HALF MILLION DOLLAR OPERATION. IF YOU PUT OUR NETWORK TOGETHER, MORE THAN 15 MILLION DOLLARS PROVIDING PROGRAMS AND SERVICES TO FAMILIES THAT ARE FIGHTING THIS DISEASE NOW, SO FINANCIAL SUPPORT AND INFORMATION SUPPORT AND IT IS A HUGE AND ACTUALLY JEN FIR IS HERE FROM DC AGAIN ONE OF OUR NETWORKS. WE ARE ACROSS THE COUNTRY. WE ARE THE LARGEST PUBLISHER OF HEALTH CANCER BOOKS IN THE COUNTRY AND INFORMATION. AND ACTUALLY GOING TO THE WHOLE ISSUE OF TISSUE DONATION, WE RECENTLY PUBLISHED A BOOK ON DIPG, THE ONLY BOOK IN THE WORLD AND WILL A CHAPTER IS DEVOTED TO THE IMPORTANCE OF POST MORTEM TISSUE DONATIONS AND WE ARE IN THE PROCESS OF WRITING A BOOK ON PALLIATIVE CARE AND THAT IS ALSO GOING TO HAVE A CHAPTER IN IT ON THE IMPORTANCE OF TISSUE DONATION AND PORT MOTOR EM TISSUE DONATION. SO, ALL OF THESE BOOKS GO OUT TO THESE FAMILIES DIAGNOSED WITH NO CHARGE. WE INITIATED TARGET, GOT INITIAL FUNDING FROM -- MALCOLM KNOWS THIS. FROM THE NCI AND AC. TO HAVE AN INITIAL CONFERENCE THAT THEN LED TO THE TARGET FUNDED INITIATIVE. WE TALKED ABOUT INTERNATIONAL INITIATIVES. SO WE SIT ON THE INTERNATIONAL CONFEDERATION OF CHILDHOOD CANCER ORGANIZATIONS, WHICH IS A COLLABORATIVE GROUP UMBRELLA THAT IS A PARTNER WITH COP, WHICH GREG IS ON THE COP BOARD. THE UICC, UNITED INTERNATIONAL AGAINST CANCER AND THEN THERE IS A COMMIT THEY IS RUN THAT FUNDS A LOT OF CANCER PROGRAMS IN DEVELOPING COUNTRIES AND I WANT TO COMMENT ABOUT ONE OF THE ORGANIZATIONS THAT IS A PARENT ORGANIZATION UNDER ICCPO, IS IN IRAN. AND WE THINK OF IRAN AS A DEVELOPED COUNTRY AND THEY CAN'T HAVE A CHILDHOOD CANCER PRIORITY. THEIR ORGANIZATION IS CALLED MAHAK AND THEY RAISED $65 MILLION A YEAR FOR CHILDHOOD CANCER. AND SO AGAIN, HERE WE ARE IN THE U.S. AND WE ARE GOING OKAY, LIKE $5 MILLION HERE ON -- $65 MILLION IN IRAN FOR ONE ORGANIZATION. SO THEY HAVE TAKEN CHILDHOOD CANCER AS A MAJOR PRIORITY. AND THEN PATIENT NAVIGATION I SHOWED WITH MARLY. AND THEN AGAIN, THERE IS ANOTHER EXAMPLE. SO MARLY WAS DIAGNOSED AND THEN SHE RELAPSED TWICE. I WAS ACTIVE IN HER CARE AND WHAT SHE WAS RECEIVING AND THERE WAS DELAYS IN TRANSPLANTS AND A BUNCH OF ISSUES BUT SO, IT WAS BECAUSE OF THE CONFERENCE IN SAN DIEGO. THERE WAS A TALK ON EPIZYME AND HAVING A NEW DRUG THAT THEY WERE LOOKING AT THAT TARGETED MLL REARRANGEMENT. I CONTACTED THAT COMPANY. THE DRUG IS CALLED EPZ5676. AND THEY WERE JUST IN A PHASE I ADULT TRIAL SO WE COULDN'T GET THE DRUG FOR MARLY. WHICH OBVIOUSLY WAS VERY SAD. SO A LOT OF RECOMMENDATIONS HERE. I THINK MESSAGING IS ESSENTIAL AND REALLY, REALLY IMPORTANT. MESSAGING THEY HEARD FOR SO MANY YEARS OUT OF THE NCI, OUT OF SO MANY PLACES IS THAT WOW, WE HAVE DONE SUCH A GREAT JOB, WE CURED CHILDHOOD CANCER IT'S WONDERFUL. 90% OF KIDS WITH CANCER ARE CURED. 80% OF KIDS WITH ALL ARE CURED. WE ARE HURTING OUR KIDS BY SAYING THIS. INSTEAD OF LIKE, WHAT TINA WAS SAYING, THIS IS THE LEADING CAUSE OF DISEASE AND DEATH OF OUR CHILDREN. YOU CAN SEE MOST OF OF THESE ADVOCATES ARE CHILDREN AND HAVE DIED AND THOSE HAVE HAVEN'T ARE LIVING WITH THE LATE EFFECTS LIKE MY DAUGHTER. WE HAVE NOT DONE THEM JUSTICE. SO I THINK WE NEED TO HAVE A PEDIATRIC CANCER ADVOCATE BOARD ON THE NCI COMMUNICATION ROUNDTABLE SO WE CAN CORRECT THAT INFORMATION AND THAT MESSAGING. MESSAGING CAME UP THIS MORNING THAT 80% OF KIDS WITH CANCER OF NON-CLINICAL TRIALS. THE REPORT THAT CAME OUT AT THE NCANISM SEPTEMBER SAID THAT THERE ARE 4000 CHILD ON COG TRIALS. RECENT REPORT THAT CAME OUT OF THE AMERICAN CANCER SOCIETY SAID INCIDENTS ROUNDED UP ABOUT 16,000. SO IF YOU TAKE 4000 KIDS ON TRIAL AND 16,000 KIDS INCIDENTS A YEAR. THAT'S 25%, NOT 80. THAT'S ANOTHER MESSAGE OUT THERE. I REMEMBER A FEW YEARS AGO, I WENT MENTION THE ORGANIZATION BUT IT WAS A ADULT CANCER ORGANIZATION, PUT OUT A FULL-PAGE AD ADD ON THE BACK OF THE "NEW YORK TIMES" ON HOW BASICALLY 95% OF KIDS WITH CANCER WERE ENTERED INTO CLINICAL TRIALS. THAT'S WHY THEY GOT CURED. AND WE NEED TO DO THAT FOR ADULTS. I WAS SO ANGRY BECAUSE IT WAS WRONG INFORMATION. IT'S KIWI HAVE ACCURATE INFORMATION AND WE NEED THE PEDIATRIC ADVOCATE VOICE ON THAT. FUNDING. WE TALKED ABOUT THAT. OUR PRIORITY. WHERE IS OUR PRIORITY? AGAIN, THE WAR ANALOGY. WHAT WOULD YOU DO IN WAR? IT'S CORRECT. THE GOVERNMENT ENDORSES AND SUPPORTS IT AND AREN'T OUR KIDS WORTH MORE THAN 4%? REALLY? WE ALL HAVE CHILDREN. WE ALL GIVE THEM OUR INHERITANCE WHEN WE DIE. WE GIVE THEM 100%. WE GIVE THEM EVERYTHING WE HAVE. AREN'T OUR CHILDREN WORTH MORE THAN 4%? IN TERMS OF RESEARCH WORKFORCE AND PETER TALKED ABOUT THAT, WE DEFINITELY NEED TO EXPAND THE INTRAMURAL AND EXTRAMURAL FUNDING OPPORTUNITIES FOR SCIENTISTS SO WE CAN BRING SCIENTISTS IN THE FIELD AND BRING CLINICIANS INTO THIS FIELD. WE DON'T DO THAT, THEN NO MATTER HOW MUCH MONEY WE HAVE, WE WON'T HAVE THE WORKFORCE DOING THE WORK. REPRESENTATIONS. NANCY MENTIONED THIS, WE NEED TO MANDATE PEDIATRIC CANCER REPRESENTATION ON THE NCAB. ON THE BOARD OF SCIENTIFIC ADVISORS AND THE PRESIDENT'S CANCER PANEL AND ON THE ADVISOR COMMITTEE. THEY NEED TO HAVE THIS VOICE. IF WE CAN'T CHINE THE LIGHT ABOUT CHILDHOOD CANCER ON THESE COMMITTEES, HOW DO WE EXPECT PEOPLE TO KNOW WHAT IS HAPPENING WITH THESE KIDS? AND THEN WE NEED TO ALSO INCLUDE ADVOCATE REPRESENTATION ON THE PEDIATRIC CANCER STEERING COMMITTEES AND THERE HAS TO BE EXPERTS. AND I KNOW THERE ARE EXPERTS ON EXPERIENCE BY THOSE ADVOCATES SO THEY REALLY CAN BE EFFECTIVE ON THE COMMITTEES ON TARGETING THE SCIENTIFIC BOARD OF ADVISERS. I SUGGEST THAT WE DO HORIZON MEETINGS. PICK ONE OR TWO CANCERS, WHETHER IT IS DIPG, JOHN MCIN TASH WAS HERE. HE LOST HIS SON. WE TALKED ABOUT IT AROUND THE TABLE. AND I KNOW DAVID IS DOING A LOT OF INITIATIVES. THIS IS A DISEASE THAT ALL THE KIDS DIE. THEY ALL DIE. ALMOST WITHIN A YEAR. THE AVERAGE IS 9 MONTHS AND AVERAGE AGE OF DIAGNOSIS IS 8 YEARS OLD. SO AGAIN, PICTURE YOUR CHILD. THEY ARE IN GRADE III AND 4 AND THEY ARE PLAYING SOCCER AND THEN A YEAR FROM NOW THEY ARE DEAD. IT'S NOT A PLEASANT DEATH. THESE KIDS LOSE ALL 80 TOW TALK AND MOVE AND THEY GO INTO HIGH DOSE STEROIDS. I KNOW CHILDREN'S WHOSE SKIN TORN OPEN FROM THE STRETCH MARKS. IT'S A HORRIBLE DISEASE AND IT IS WORTHY OF A HORIZON MEETING. CROSS INSTITUTE COMMUNICATION. THIS IS ABSOLUTELY ESSENTIAL AS WELL. WE HAVE OUR OWN COMFORT ZONE WITHIN THE NCI. OTHERS HAVE DONE THIS. LIE AUTISM. WE NEED A COMMIT THEY WILL LOOK ACROSS INSTITUTES, NICHD FOR EXAMPLE AND ALSO TRND, IT'S DRUG DEVELOPMENT FOR RARE DISEASES. WE HAVE A RARE DISEASE. THERE IS NOT ONE DRUG WITHIN THAT TRND LIST OF DRUGS THAT IS TARGETING CHILDHOOD CANCER. THERE IS ONE FOR ALS AND ALL THESE RARE DISEASES BUT NOTHING FOR CHILDHOOD CANCER AND THIS MIGHT BE A WAY AGAIN FOR US TO TAKE THE DRUG DISCOVER DISCOVERY AND THEN MOVE IT AGAIN ACROSS INSTITUTE INTO TRND. AND IF WE DON'T DO THIS, THEN THIS IS WHAT HAPPENS. SO MARLY DIED DECEMBER 12, 2013, TWO WEEKS BEFORE CHRISTMAS. SHE WAS AN ONLY CHILD. AND THERE IS AN ESTIMATED 500 CHILDREN, WHO30 ADOLESCENTS THAT WILL BE DIAGNOSED IN 2014. AT THIS POINT IN TIME, HALF WILL CONTINUE TO DIE AND IT'S NOT ACCEPTABLE. WE NEED TO GIVE OUR KIDS BETTER WEAPONS TO FIGHT THE WAR ON CHILDHOOD CANCER AND THIS IS THE TAG PHRASE FOR AMERICAN CHILDHOOD CANCER ORGANIZATION. AND TING IS SO TRUE. BECAUSE KIDS CAN'T FIGHT CANCER ALONE. THEY ABSOLUTELY NIDUSES. WE NEED INTELLIGENCE AND WE NEED THE PEOPLE THAT ARE THERE TO HELP THEM REACH THAT GOAL AND WIN THAT BATTLE. IT IS ESSENTIAL. [ APPLAUSE ] >> THANK YOU VERY MUCH. SARAH. SARAH FROM THE AMERICAN CANCER SOCIETY CANCER ACTION NETWORK. >> THANK YOU. SO, I WANT TO THANK NCI STAFF FOR INVITING ME AND I WANT TO ACKNOWLEDGE ALL THE YEARS OF ADVOCACY EXPERIENCE THAT HAS BEEN ON THIS PANEL. IT'S GREAT TO BE PART OF SUCH AN IMPRESSIVE GROUP AND IMPRESSIVE AUDIENCE. I WANT TO TAKE A MINUTE TO EXPLAIN WHAT ACS IS. EVERYBODY KNOWS WHAT THE AMERICAN AMERICAN CANCER SOCIETY IS. I KNOW SOME OF YOU MAY THINK THAT ACS CAN IS AN EXPRESSION WE NEED TO INFLATE OUR SELF-ESTEEM. ACS CAN! WELL, IT'S ACTUALLY AN ACRONYM. IT STANDS FOR AMERICAN CANCER SOCIETY CANCER ACTION NETWORK. IT'S A MOUTHFUL. CONSIDER IT ALPHABET SOUP. SOMETIMES I CAN'T GET OUT OF MY MOUTH. WHAT IT MEANS IS THAT WE ARE HERE TO TAKE ACTION WITHIN OUR POLITICAL SYSTEM ON BEHALF OF CANCER PATIENTS AND THEIR FAMILIES. I WANT TO START WITH SOMETHING TIMELY AS MOST OF YOU KNOW, ACS RECENTLY RELEASED A SPECIAL SECTION ON CANCER IN CHILDREN AND ADOLESCENCE IN THE ANNUAL FACTS AND FIGURES REPORT ON CANCER CASES AND DEATHS IN THE CURRENT YEAR. CANCER REMAINS THE SECOND LEADING CAUSE OF DEATH FOR CHILDREN ONLY SECOND TO -- AND IT DEPARTMENT SEEM TO BE CHANGING. THIS IS 1-285 CHILDREN IN THE UNITED STATES WILL BE DIAGNOSED. FROM 1975-2010, OVERALL INCIDENTS OF PEDIATRIC CANCER RISING AND SOME OF THAT MAY BE DUE TO BETTER DIAGNOSIS, SOME OF IT MAY NOT. THERE ARE ALMOST 380,000 SURVIVORS. WHICH MEANS THAT THERE IS ONE-530 YOUNG ADULTS BETWEEN 20-39, MY AGE, THAT IS A CHILDHOOD CANCER SURVIVOR. STATISTICS DON'T SHOW THE FACES AND THE FAMILIES AND THE COMMUNITIES THAT ARE TOUCHED BY CHILDHOOD CANCER AND THIS IS WHERE ACS COMES INTO PLAY. ADVOCATING FOR PATIENTS AND FAMILIES. PRIORITY FOR ACS CAN IS PROTECT AND INCREASE FEDERAL FUNDING FOR CANCER RESEARCH AT NIH, NCI. BUT IN IN CONGRESSIONAL CLIMATE IT'S DIFFICULT TO CHANGE THE LANGUAGE FROM PROTECT FUNDING INSTEAD OF INCREASING. WE WORKED ON A NUMBER OF BILLS WHICH BECAME LAW IN 2012 THAT FOCUS ON PEDIATRIC CANCER INCLUDING BBCA, PRA. WE DISCUSSED A LITTLE BIT OF THAT. AND WE ENDORSED CHILDHOOD CANCER SURVIVORS QUALITY OF LIFE ACT AND REAUTHORIZATION FOR THE CAROLYN PRICE WALKER CHILDHOOD CANCER ACT. ACS CAN PARTICIPATES IN THE ALLIANCE FOR CHILDHOOD CANCER, COALITION MEMBER ORGANIZATIONS AND ADVANCING CHILDHOOD CANCER ISSUES. ONE OF OUR BIGGEST SUCCESSES FOR CHILDREN IS THE WORK ON THE AFFORDABLE CARE ACT. AMONG THE MANY ITEMS THAT ARE INCLUDED IN THAT REPORT HOW CLIENTS ARE COVERED WHEN THEY GET SICK. NEW HEALTH PLANS COVERAGE IN CHILDREN AND AS WELL AS ADULTS WITH PRE-EXISTING CONDITIONS HEALTH PLANS ARE BARRED FROM SPENDING LIFETIME DOLLAR CAPS AND COVERAGE. THE CHALLENGE I ALLUDED TO EARLIER, IS THAT CONGRESS HASN'T WANTED TO ACT. THIS NONACTION HAS SPLINTERED ALL THE CANCER COMMUNITY AND NOT JUST PEDIATRIC CANCER. THIS NONACTION FORCED THEICANTER COMMUNITY AS A WHOLE TO SAVE THEMSELVES AND INDIVIDUAL PRIORITIES. THIS HAS LED THE COMMUNITY TO BE LESS EFFECTIVE. WE'LL TAKE WHATEVER WE CAN GET. NOW THE STRENGTHS OF THE PEDIATRIC COMMUNITY AND ONE OF THE WEAKNESSES IS IT IS A BROAD DIVERSE COMMUNITY THAT IS FIERCELY PASSIONATE. IT SEEMS THAT ALMOST EVERYONE THAT WORKS IN HIGHLAND HOOD CANCER ADVOCACY HAS BEEN PERSONALLY TOUCHED. THIS GIVES US STRENGTH BUT IT ALSO LEADS TO A NARROW FOCUS. ALL ORGANIZATIONS ARE GOING TO HAVE THEIR AUTHORITIES BUT SOMETIMES THERE NEEDS TO BE SHARED ONES SO WE CAN ALL PUSH THE GAS PEDAL TOGETHER. SOMETIMES THE COMMUNITY CHOOSES TO FOCUS ON INITIATIVES AND SOMETIMES LARGE NONDISEASE SPECIFIC PROJECTS CAN BE JUST AS IMPORTANT AND CHILDHOOD CANCER PATIENTS SURVIVORS AND FAMILIES. ONE ISSUE THAT CAME TO MIND WAS MEDICATE EXPANSION. THIS IS NOT AN EXAMPLE FOR THIS AUDIENCE BUT IT IS AN EXAMPLE OF WHAT WE CAN DO FOR SURVIVORS. I WOULD LIKE TO CLOSE BY SUGGESTING THAT NIH, NCI AND FDA NEED TO WORK MORE CLOSELY WITH STAKEHOLDERS TO HELP POINT OUT WHERE THERE CAN BE MOVEMENT AND PROGRESS. IF ANYONE WATCHES HOUSE OF CARDS, MAY I SUGGEST A FEW BAD CHANNEL CONVERSATIONS? NO ONE WATCHES HOUSE OF CARDS? ALL RIGHT. THIS MEETING IS A PERFECT EXAMPLE OF THAT. WE NEED GUIDELINES. WE NEED GUIDELINES TO TAKE IT TO THE VOLUNTEERS AND WE NEED SUPPORT AND EXPERTISE TO TAKE IT TO THE VOLUNTEERS SO WE CAN EXPLAIN IT AND SHOW WHY THESE THINGS ARE SO IMPORTANT. AND I WANT TO SAY THANK YOU. [ APPLAUSE ] >> THANK YOU, SARAH. PETER, YOU ARE UP. PETER MAY BARRY FROM SAINT BALDRICK'S FOUNDATION. >> THANK YOU VERY MUCH. I LOAD TO JOIN THE OTHERS IN THANKING NCI AND NIH FOR PUTTING ON THIS VERY SAFER VERY IMPORTANT AND INSTRUCTIVE AND INFORMATIVE WORKSHOP. I AM THE NEW KID ON THE BLOCK HERE. I HAVE BEEN A PART OF THE SAINT BALDRICK'S FOUNDATION SINCE MID-OCTOBER OF 2013. AND I JUST COME TO MEET MANY OF YOUR PEOPLE IN THE ROOM OVER THE PAST FEW MONTHS. AND I HAVE BEEN SO TREMENDOUSLY IMPRESSED AND HUMBLED BY THE KNOWLEDGE AND THE DEDICATION AND THE PASSION FOR VIRTUALLY EVERYBODY WHO IS IN THIS ROOM. WE ALL TRYING TO FIND AN ANSWER. WE ALL ARE DISCOVERING WHAT THE CHALLENGES ARE, WHAT THE STRUGGLES ARE. AND A LOT OF THE ROAD BLOCKS ARE COMING IN THE LINE. AND AS THEY SAY, AS THE CULTURE GOES, A PROBLEM THAT IS WELL DEFINED IS HALF SOLVED. NOW, IN THIS CASE, WHAT WE ARE TALKING ABOUT IS MONEY AND DRUG DEVELOPMENT AND CONGRESS, WE ARE TALKING ABOUT GLOBAL REGULATORY FORCES. SOMETIMES A PROBLEM IS SOLD AND MAYBE THAT'S NOT ENOUGH. BUT I THINK WITH THE ATTENTION THAT NIH AND NCI AND FDA OF COURSE GIVING THIS INCREDIBLE IMPORTANT ISSUE OVER THE PAST FEW MONTHS, I THINK WE ARE ON OUR WAY A LITTLE BIT BETTER THAN WE WERE A COUPLE EVER YEARS AGO AS I UNDERSTAND IT SAINT BALDRICK'S, WE WERE FORMED OUT OF THE AMBITIONS OF THREE GOOD FRIENDS WHO WERE SITTING AROUND HAVING A BEER. ONE SAID TO THE OTHER, IF -- I'LL BET YOU A CERTAIN AMOUNT OF MONEY YOU WOULDN'T SHAVE YOUR HEAD. AND IF YOU DO SHAVE YOUR HEAD, I'LL GIVE THAT AMOUNT OF MONEY TO WHATEVER CHARITY YOU DESIRE. AND THE THIRD GUY SAID, I'LL MATCH WHATEVER HE GIVES. THAT WAS IN 2000. BY 2005, THE CONCEPT HAS GONE SO VIRAL, WE HAVE BECOME THE LARGEST PRIORITY SECTOR SOURCE OF FUNDING FOR PEDIATRIC ONCOLOGY AND RESEARCH. LAST YEAR WE RAISED $33.7 MILLION FROM 1400 EVENTS THAT HAD 58,500 PEOPLE SHAVING THEIR HEADS UNDER THE CONCEPT OF, HOW MUCH WILL YOU DONATE FOR CHILDHOOD CANCER RESEARCH TO SEE ME SHAVE MY HEAD? AND IN THE SPIRIT OF QUADW, ONE OF OUR PRINCIPALS IS, IF IT'S FUN, THEY WILL COME. OUR EVENTS ARE BOISTEROUS AND OUT GOING AND COMPETITIVE. WONDERFUL GOOD TIMES. BUT WE TAKE THAT MONEY AND WE PUT IN THE RESEARCH. AND AGAIN, WE GRANTED ONE OF THE 24.5 MILLION DOLLARS FOR CHILDHOOD CANCER LAST YEAR. AND THE GRANTS ARE ARE STILL BEING FUNDED. WE FUND VIRTUALLY EVERY STAGE AND TYPE OF RESEARCH INCLUDING TRAINING AND EARLIER CAREER GRANTS. GRANTS TO ESTABLISH RESEARCHERS AND SUPPORTIVE CARE RESEARCH GRANTS, CONSORTIA GRANTS AND THE CHILDREN'S ONCOLOGY GROUP FOR WHICH WE ARE SO HUMBLED BY THE SHOUT OUT THAT WE GOT OUT THIS MORNING AS WELL AS THIS TEAM. OUR NEW CEST FOR INTERNATIONAL SCHOLARS. MOST OF THESE ARE LOW OR MIDDLE-INCOME COUNTRIES TO PREFER THE SITE. ONE OF THE OTHER THINGS WE ARE VERY PROUD TO GIVE A SHOUT OUT ABOUT IS OUR STAND UP TO CANCER DREAM TEAM WHICH WAS LAUNCHED IN JULY OF 2013 AND MADE UP OF RESEARCHERS FROM 7 STATUTES IN NORTH AMERICA. THE DREAM TEAM GOAL IS TO CREATE NEW THERAPIES BASED ON TUMOR GENOMICS AND WHAT MAKES THE CANCER CELLS DIFFERENT FROM THE REST OF THE BODY. THIS BRINGS EXPERTS TOGETHER THAT DRIVE AND SUSTAIN CANCER CELLS WITH EXPERTS IN IMMUNOLOGY, STUDY THE HUMAN IMMUNE SYSTEM. THIS IS THE FIRST TIME RESEARCHERS FROM THE TWO DISTINCT FELD HAVE COME TOGETHER TO BALLING THE PROBLEM OF CHILDHOOD CANCER. THUNDER PROJECT, LARGE NUMBER OF TUMOR SAMPLES HAVE BEEN SERVED AS THE BASIS FOR DISCOVERING NEW TARGETS. INVESTIGATORS HAVE IDENTIFIED AL. K, A TARGET IDENTIFIED IN NEUROBLASTOMA COULD SERVE AS A TARGET FOR CHILDHOOD BRAIN TUMORS AND SARCOMAS. INVESTIGATORS DISCOVERED THE PROTEIN DERIVED FROM THE MALARIA PARASITE FINDS A LARGE NUMBER OF PEDIATRIC CANCERS THAT COULD BE USED FOR IMMUNE TARGETING. WE SAID EARLIER, WE COULD BE ON THE CUSP OF THE GREATEST DISCOVERIES OF CANCER FROM ALL TIMES BASED ON THIS RESEARCH. WE ALSO HONOR KIDS AND FAMILIES. ON OUR WEBSITE ALONE, THERE ARE MORE THAN 3000 HONORED KIDS AND WE FOCUS TO GIVE A FACE AND A VOICE AS THEY MOVE THROUGH THE REST THEIR LIVES. AND WE ALSO CHOOSE KIDS PER YEAR WHO WE HIGHLIGHT, ONE OF WHICH HAS ALWAYS BEEN A DECEASED CHILD TO REPRESENT THE FACT THAT OF EVERY FIVE CHILDREN, HER DIAGNOSIS WITH CANCER, ONE WILL NOT SURVIVE. WE ESTABLISHED FUNDS AND PARTNERSHIPS. THEY ARE A WAY TO GIVE PEOPLE WHO LOST THE CHILD AND WANT TO SET UP THEIR OWN NONPROFIT THE ABILITY TO JOIN TOGETHER WITH SAINT BALDRICK'S AND HAVE ESTABLISHED FOUNDATIONS PARTNER WITH US TO FUND RESEARCH THAT IS ALREADY BEEN SCIENTIFICALLY APPROVED. LASTLY, I'D LIKE TO TALK ABOUT OUR ADVOCACY PROGRAMS. WE HAVE MORE THAN 80,000 ACTIVE VOLUNTEERS AND HUNDREDS OF THOUSANDS OF DONORS AND LAUNCHED ADVOCACY PROGRAM TO ENCOURAGE PEOPLE TO QUOTE, SPEAK UP FOR KIDS WITH CANCER. OUR EFFORTS ARE INTENDED TO PROMOTE FEDERAL FUNDING FOR CHILDHOOD CANCER RESEARCH AND INFLUENCE LEGISLATION AND MAKE CHANGES OF FEDERAL REGULATIONS. OUR BOARD OF DIRECTORS IS COMMITTED TO ADVOCACY EFFORTS AND SUPPORTS GOALS INCLUDING PROPER ADDRESS TO PEDIATRIC DRUG ONCOLOGY DRUG SHORTAGES AND SPOORS FOR THE CHILDHOOD CANCER ACT AND FEDERAL FUNDING FOR CHILDHOOD CANCER RESEARCH AND SUPPORT FOR CANCER APPROPRIATIONS AND CREATING HOPE ACT. WE WORK WITH MEMBERS OF THE CONGRESSIONAL CHILDHOOD CANCER CAUCUS AND THE U.S. HOUSES OF REPRESENTATIVES AND WITH THE SENATE CANCER COALITION AS WELL AS REGULATORY OFFICIALS WITHIN THE NIH, NCI, FCC AND DOD. WE ARE ALSO ACTIVE PARTICIPANTS IN ALLIANCE FOR CANCER RESEARCH AND ONE VOICE AGAINST CANCER AND LASTLY, OUR ADVOCACY TEAM HAS MORE THAN 5 DECADES OF COMBINED EXPERIENCE AND DEDICATED TO THE SAINT BALDRICK'S CAUSE IN SOLVING THE PROBLEMS WE ALL HAVE BEEN DISCUSSING TODAY. [ APPLAUSE ] >> I'M THE PRESIDENT OF THE COALITION AGAINST CHILDHOOD CANCER AND WE ARE A COLLABORATIVE NETWORK OF ORGANIZATIONS AND INDIVIDUALS SUPPORTING AND SERVING THE CHILDHOOD CANCER COMMUNITY AND WHILE WE HAVE BEEN IN THE WORKS FOR A COUPLE OF YEARS, WE ARE NEWLY FOUNDED IN THE MILT OF 2013 AND I'M SO HAPPY TO BE INCLUDED IN THE CONVERSATION TODAY. WHAT I UNDERSTAND, MY PERSONAL EXPERIENCE WITH THE CHILDHOOD CANCER ORGANIZATION GOES BACK A LITTLE BIT LONGER THAN LAST YEAR. I HAD A DAUGHTER WHO WAS DIAGNOSED IN 2002 AND WHO SURVIVED NEUROBLASTOMA FOR 7 YEARS BEFORE SHE SUCCUMBED AND WHAT WAS AMAZING TO ME IS THAT I THOUGHT I UNDERSTOOD A LOT ABOUT ACADEMICS AND ACADEMIC RESEARCH AND ABOUT THE WORLD OF ADVOCACY BECAUSE OF OTHER THINGS I HAD BEEN INVOLVED IN. WHAT I DIDN'T UNDERSTAND WAS THE LANDSCAPE AND HOW FRAGMENT TODAY IS. WHEN I START THINKING ABOUT BARRIERS TO DRUG DEVELOPMENT, PETE YOU SAID 100 DIFFERENT KINDS OF CANCERS, CHILDHOOD CANCERS. WHILE THE SOURCES OF FUNDING PRIMARILY FROM THE NIH, I THINK THAT PETER JUST SAID 33 MILLION WAS RAISED, 24 MILLION IN AWARDS LAST YEAR RESEARCH IS GOING ON AT MULTIPLE INSTITUTIONS AROUND THE COUNTRY. IF YOU'RE A RESEARCHER OR AN ADVOCATE, THERE IS A LOT OF INFORMATION OUT THERE THAT IS IN THE GAPS. WHAT IS BEING FUNDED. WHO IS FUNDING WHAT. WHAT ARE THE PROCESSES AND WHAT ARE THE POLICIES? AND SO WHEN YOU TAKE THAT FRAGMENTED LANDSCAPE AND OVERLAY ON TOP OF THAT, THE ADVOCACY COMMUNITY, YOU HAVE THIS INFORMATION GAP AND IT COMES FROM THE NATURAL FRAGMENTATION OF THE RESEARCH ENVIRONMENT BUT YOU HAVE MANY HUNDRED THOUSANDS OF INDIVIDUAL ADVOCACY ORGANIZATIONS AND SOME OF THEM ARE FAIRLY NARROW. THOUGH FOCUS ON ONE PARTICULAR DISEASE OR RAISE MONEY FOR RESEARCH AT ONE PARTICULAR HOSPITAL OR STAY IN ONE PARTICULAR REGIONAL AREA. THERE ARE AS WE VISITED HERE TODAY, BROADER MODELS THAT WERE NATIONAL AND SYNDICATION APPROACH OR A FEDERATION APPROACH TO SPREAD INFORMATION OUT AND LIKE MAUREEN TALKED ABOUT IN HER DEEP AND BROAD EXPERTISE IN A PARTICULAR AREA, THESE ARE ALL EXTREMELY IMPORTANT AND VIABLE MODELS FOR ADVOCACY AND THERE IS NOTHING TO BE PASSIONATE PEOPLE TRYING TO DO GOOD WORK WITHIN THE AREA THEY FEEL COMFORTABLE DOING. I WOULD SAY DESPITE WHAT IS GOING ON, THERE IS A PRETTY BIG INFORMATION GAP. I DON'T FINISH THERE IS ANYBODY IN THIS ROOM THAT YOU HAVEN'T LEARNED SOMETHING TODAY. IT FILLS IN THE INFORMATION GAP. IN GENERAL, WHAT I WOULD SAY IS, THAT ONE OF THE WAYS TO DEAL WITH AN INFORMATION GAP IS TO EXPAND INFORMATION RICHNESS, THE QUALITY OF YOUR INFORMATION, AND INFORMATION REACH. SO YOU PLANNED THIS WORKSHOP TODAY. PEOPLE ABLE TO KNOW WHAT WAS SAID HERE AT THIS MEETING WOULD BE, OR HAVE A MUCH SMALLER INFORMATION GAP AND ALSO BECAUSE OF THE WAY YOU'RE OPERATING, YOU HAVE ALMOST AT LEAST THEORETICALLY, INEFFICIENT INFORMATION REACH BECAUSE YOU CAN PUT THIS ON THE INTERNET. YOU CAN PUT OW YOUR WEBSITE, YOU'RE BROADCASTING IT. SO POTENTIALLY YOU HAVE GREAT INFORMATION RICHNESS AND REACH. WE DON'T NECESSARILY KNOW ABOUT THIS OR HAVE IN ALL THESE DIFFERENT POCKETS -- I LIVE IN BRIAN TEXAS. WE HAVE -- I TEACH AT TEXT AT A&M IT'S FAR. I DON'T HAVE A CLUE ABOUT WHEN I FIRST GOT AN IN I HAVEITITION. HE IT SAID IT WAS THE 64'S DIRECTORS MEETING AND I WONDERED WHAT HAD HAPPENED THE PREVIOUS 63 TIMES BECAUSE I WAS NOT AWARE. I HAD A BIG INFORMATION GAP AND I KNOW OF THE FAMILIES THAT ARE THE 14,000 CHILDREN THAT ARE DIAGNOSED THIS YEAR. THE 380,000 SURVIVORS. I'M PRETTY SURE THAT THEY HAVE INFORMATION GAPS THAT COULD BE FILLED BY THIS. ONE OF THE THINGS I'D LIKE TO TALK ABOUT IS THE WAY THESE ORGANIZATIONS, ADVOCACY GROUPS WORK ON FILLING AND CLOSING THE INFORMATION GAP AND WHAT THE ORGANIZATION I'M INVOLVED IN DOES TO NOT REPLACE WHAT THEY ARE DOING BUT TO AMPLIFY WHAT THEY ARE DOING. THE COALITION AGAINST CHILDHOOD CANCER AN ORGANIZATION OR SUPPORT NETWORK THAT HAS A MISSION TO FOSTER AND COORDINATION ACTION AND KNOWLEDGE AND LEARNING LEARNING AND BROAD-BASED CLAPERATION IN THE INITIATIVES IN FOUR AREAS, ADVOCACY, SUPPORT, RESEARCH AND TREATMENT, FAMILY SERVICES AND AWARENESS BUILDING. AND THIS IS NOT MEANT TO REPLACE ANY OF THAT HUGE NUMBER OF ADVOCACY GROUPS IT'S TO HELP PROVIDE AND CLOSE THE GAP IN INFORMATION BY MAKING INFORMATION RICHER. THERE IS A TRUST AND RELATIONSHIP AMONG MEMBERS WE BUILDUP BY COMING INTO CONTACT WITH EACH OTHER. BY WORKING ON PROJECTS WITH EACH OTHER AND SERVING TOGETHER IN WAYS THAT LET ME SAY TO SOMEONE WHO LIVED IN TAN ANTONIO OR BOLDURE. I THINK YOU SHOULD LISTEN IN TODAY BECAUSE I THINK IT IS IMPORTANT. IT'S NOT BECAUSE I SAW IT ON THE INTERNET, OR GOT POSTED SOMEWHERE, IT'S BECAUSE I SAID, TO SOMEBODY I TRUST, THIS IS GOING TO BE A COOL THING. SO, IT DOES BOTH EXPAND THE REACH THROUGH MEMBERSHIP ORGANIZATIONS BEYOND ONE ORGANIZATION, EVEN A FEDERATED ORGANIZATION, AND IT CREATES TRUST RELATIONSHIP THAT CLOSES THE GAP. OUR FOUR GOALS ARE AROUND THESE PILLARS IN THE PREVIOUS SLIDE TO OPTIMIZE ORGANIZATIONS AND: [ READING ] AND THE PIECE WE DIDN'T TALK ABOUT IS FAMILY SERVICES. INCREASE AWARENESS AND PROMOTE COLLABORATION AMONG FAMILY AND PATIENT SUPPORT GROUPS. THERE IS A LIFE OUTSIDE OF THE RESOURCE -- RESEARCH PROCESS THAT EFFECTS THESE FAMILIES. WHEN YOU BECOME A MEMBER OF THE COALITION AGAINST CHILDHOOD CANCER, YOU MAY JUST STEP INTO THE CONE AND WORK ON THINGS THAT ARE JUST ONE-ON-ONE COOPERATIVE. YOU MIGHT MEET SOMEONE. IT MIGHT ENHANCE YOUR PERSONAL RELATIONSHIP. SO YOU KNOW SOMEONE THAT YOU DIDN'T KNOW. AND IN OUR CASE, LET ME HIGHLIGHT A COUPLE OF THINGS. SO THE BE POSITIVE FOUNDATION IS ONE OF THE FOUNDING MEMBERS OF THE THE COALITION AGAINST CHILDHOOD CANCER AND JOE MCDUMB AN AND REPRESENTATIVES FROM SOLVING KIDS CANCER GOT TO TALKING AND THEY DECIDED THEY COULD CO-FUND A DENDRITIC CELL RESEARCH PROJECT FOR NEUROBLASTOMA THAT CREATED A COMPLETE RESPONSE. THEY MET EACH OTHER AND WORKED THROUGH THE COALITION. IT WAS BECAUSE THEY KNEW EACH OTHER. ANOTHER EXAMPLE IS THAT. ANOTHER ORGANIZATION IS PRETTY GOD AT RAISING MONEY IN FLORIDA, BUT DIDN'T HAVE A SCIENTIFIC ADVISORY BOARD AND DIDN'T REALLY KNOW HOW TO DIRECT THEIR MONEY. AND THEY GOT TOGETHER AND USED THE REVIEW PROCESS AS ALEX TO FUND RESEARCH THAT THEY WOULDN'T -- IT WOULD HAVE BEEN MORE LIKE CROSSING A GUARD TO FIND THAT RESEARCH. WE ALSO HAVE AS YOU MOVE THROUGH THE CONE AND BECOME MORE INVOLVED IN THE COALITION AGAINST CHILDHOOD CANCER, THE OPPORTUNITY TO FLOAT TOWARDS ORGANIZATIONS THAT DO THE SAME SORTS OF THINGS THAT YOU DO. SOMETIMES INTEREST GROUPS ARE A VERY INTERESTING EXAMPLE OF THAT. WE HAVE A RESEARCH INTEREST GROUP. WE ALSO HAVE A HAT TRICK. -- THE GRANDPARENTS. SOME OF THE COALITION MEMBERS HAVE GOTTEN TOGETHER AND CREATED AN INTEREST GROUP CALLED GRANDPARENTS IN ACTION AND THEY GO AND LOBBY THE MEMBERS OF CONGRESS AND OTHER PEOPLE AND HAVE A DIFFERENT KIND OF PERSPECTIVE IN A WAY YOU CAN NOT TALK ABOUT JUST LOSING YOUR CHILD BUT IF YOU HAVE TO WATCH YOUR ADULT CHILDREN WATCH THEIR OWN CHILDREN DIE, AND THEY WOULDN'T HAVE KNOWN EACH OTHER HAD THEY NOT GOTTEN TOGETHER THROUGH THIS ORGANIZATION AND FOUND THAT COMMON INTEREST. WE HAVE AN ADVOCACY GROUP THAT EVERY TWO MONTHS GETS ON THE PHONE AND ACTS AS A CLEARING HOUSE FOR INFORMATION ABOUT WHAT IS GOING ON IN ADVOCACY. IN UPON RESEARCH, WE HAVE A GROUP THAT IS FORMING AND TRYING TO UNDERSTAND HOW SOME OF THE IDEAS THAT THEY ARE KICKING AROUND, WHETHER WE SHOULD TRY AND RESEARCH ADVOCATES TO GO TO CONFERENCES OR COME TO NCI AND ADVOCATE TO CAPITOL HILL AND THE EXECUTIVE BRANCH. WE ALSO WORKED ON COLLABORATION PROJECTS THAT WERE ENDORSED AND SUPPORTED BY THE GROUP. FOR INSTANCE TRYING TO GET ALL THE MEMBER ORGANIZATIONS ON THE SAME PAGE WITH THE STATIST TAKES THEY SHARE ON THEIR WEBSITE. AND TRYING TO GET THEM AND OF COURSE WE HAVE GOOD STATISTICS BUT WE DON'T ALWAYS FRAME THEM IN THE SAME WAY SO TRYING TO GET THE QUESTION RELATED TO THE WAY THE DATABASE IS SET UP IS 14 AND UNDER OR 20 AND UNDER AND WHAT THE INCIDENTS ARE. AND SO, WHAT I'D LIKE TO SAY IS I LOVE THE ADVOCATES ON THIS ORGANIZATION AND CHILDHOOD CANCER ORGANIZATIONS THAT ALLOWED IN THE COMMUNITY AND I THINK THAT THE ONES REPRESENTED HERE AND THE MANY, MANY MORE THAT ARE NOT REPRESENTED HERE ARE DOING GREAT WORK AND I THINK THAT THE COALITION IS MEANT TO NOT REPLACE WHAT THEY DO, SORE STEP ON THEIR TOES BUT AMPLIFY THE RELATIONSHIP THEY CAN DEVELOP AND CLOSE THAT GAP, THAT INFORMATION GAP THAT COMES FROM HAVING A FRAGMENTED RESEARCH LANDSCAPE AND A FRAGMENTED LANDSCAPE. CURRENTLY WE HAVE 57 ORGANIZATIONS AS SMALL AS 25,000 IN REVENUES, ANNUALLY AND 10 MILLION AND WE HAVE OTHER AFFILIATED INDIVIDUAL ADVOCATES LIKE MYSELF. AND WE ARE ABOUT TO START OUR MEMBERSHIP DRIVE PROBABLY BY THIS TIME NEXT YEAR TWICE AS BIG MAYBE LARGER. >> I APPRECIATE THE 6 GROUPS THAT GOT UP AND TALKED BECAUSE IT GIVES US AN IDEA HOW COMMITTED THIS COMMUNITY IS. THERE ARE OTHERS IN THE ROOM WHO COULD ALL TELL SIMILAR STORIES AND IF WE HAD TIME, WE SHOULD DO THAT TOO. BUT I'D LIKE TO RECOGNIZE THAT WE WILL LET THAT STAND AS ONE SMALL SMIDGEON OF THIS UNIVERSE AND BE GLAD ALL OF US ARE WORKING HARD ON IT. THIS IS SOMETHING WE ARE INTERESTED IN BECAUSE WE ARE INVOLVED IN GROUPS THAT DO RELATED WORK AND THAT THIS IS ENRICHING US BY LETTING US LEARN ABOUT ALL OF THESE ACTIVITIES. I'D LIKE TO TAKE ADVANTAGE OF THE OPPORTUNITY, WE JUST HAD SIX GREAT SPEAKERS. IF WE HAVE QUESTIONS FOR THEM AND COMMENTS AND DISCUSSION, THEN MY PLAN WOULD BE TO ALLOW YOU TO TAKE A BREAK. IT'S BEEN A LONG TIME SINCE LUNCH. AND THEN WE'LL COME BACK AND DO THE NEXT STEPS FOR DCLG. SO THERE ARE QUESTIONS FOR OUR SPEAKERS WITHIN THE GROUP? YES? >> HI. CHILDREN'S CAUSE. I WANTED TO CLEAR SOMETHING UP SINCE THERE WAS SOME ILLUSION ABOUT NOT COMING TO AGREEMENT ON THE NUMBER OF CHILDREN WHO ARE ENROLLED IN CLINICAL TRIALS. YOU HAD A NUMBER AND THEN YOU SAID WE DON'T HAVE A NUMBER. >> SO WHAT WE HAVE ARE PROBABLY ESTIMATES. BECAUSE THE TWO NUMBERS YOU NEED ARE ENUMERATOR, DENOMINATOR. WE HAVE A REASONABLE ESTIMATE OF THE DENOMINATOR AND THE NUMERATOR, YES, THE CHILDREN IN THE ON COLLIE GROUP IS THE LARGEST ORGANIZATION TO ENROLL. IT'S NOT THE ONLY ORGANIZATION ENROLLING CHILDREN. I THINK GREG PUBLISHED DATA A FEW YEARS AGO AND THE OTHER VARIABLE WHERE THE CONFUSION ARISES IS WHAT WE CALL PEDIATRIC. IS IT THE 14, 18, 19, 21? AND ALL THAT WILL IMPACT. THE HIGHEST ENROLLMENT CERTAINLY IS AMONG THE YOUNGER CHILDREN. LESS THAN 6. HISTORICALLY 60% OF THE CHILDREN ENROLL ON CHILD AND AS YOU GET OLDER, THAT ENROLLMENT FIGURE GOES DOWN AND UNFORTUNATELY IT IS THE LOWEST IN THE OLDER ADOLESCENTS. SO I THINK A REASONABLE ESTIMATE IS IF YOU LOOK ACROSS THE COUNTRY, IT IS PROBABLY APPROACHING 50% BUT NO HIGHER. I DON'T THINK IT IS A LOT LESS THAN IT HAS HISTORICALLY BEEN, BUT I THINK SOME OF THE ESTIMATES LOOKED AT EITHER SEGMENT OF POPULATIONS OR DIFFERENT NUMERATORS AND DENOMINATORS. WHAT WE KNOW IS, AS FAR AS WHERE CHILDREN ARE TREATED, 90% OF CHILDREN ARE TREATED AT A CHILDREN'S ONCOLOGY GROUP MEMBER SITE. A IS THAT DOESN'T MEAN 90% OF CHILDREN ARE ENROLLED IN A CLINICAL TRIAL. GREG YOU WANT TO EXPAND? >> I THINK THE OTHER CONFUSING THING IS NOT EVERY CHILD IS NECESSARILY ELIGIBLE FOR A CLINICAL TRIAL. AND THERE AREN'T CLINICAL TRIALS FOR EVERY SINGLE DISEASE THAT SORT OF CONSTITUTES CHILDHOOD CANCER. I THINK JOHN MAY HAVE MENTIONED THIS MORNING THAT SEVERAL YEARS AGO, BECAUSE OF RESOURCE LIMITATIONS, WE MADE A CONSCIOUS DECISION NOT TO DO CLINICAL TRIALS IN EARLY STAGE -- TUMOR BECAUSE WE WEREN'T GOING TO IMPROVE ON THE OUTSTANDING RESULTS AND INFANTS WITH NEUROBLASTOMA WHO REQUIRE MINIMAL THERAPIES, ALTHOUGH THERE ARE STILL QUESTIONS TO ASK, WE DID HAVE -- DIDN'T HAVE THE RESOURCES TO KEEP ASKING THOSE QUESTIONS. SO I THINK JUST TAKING THE NUMBER 14,000 THAT ARE DIAGNOSED AND 6000 ENROLLED IN CLINICAL TRIALS AND SAYING THAT WE ARE WRONG BECAUSE WE SAY IT IS 90%. IT'S SOMEWHAT JUSTIFIED BUT I THINK THAT AS PETER SAID, WE HAVE TO BE CAREFUL ABOUT WHAT THE NUMERATOR AND WHAT IS THE DENOMINATOR. I THINK IT IS VERY ACCURATE TO SAY THE PROGRESS THAT HAS BEEN MADE IN CHILDHOOD KENSER HAS BEEN MADE BECAUSE OF CHILDREN ENROLLING ON CLINICAL TRIALS. AND NO QUESTION 20 YEARS AGO, 90% OF CHILDREN WERE ENROLLED ON CLINICAL TRIALS BECAUSE THAT TIME REAL DECONSTITUTE THE ALMOST THE STANDARD OF CARE. >> SO WHAT I WOULD SAY IS REAL TWO POPULATIONS TO THINK ABOUT IS CHILDREN NEWLY DIAGNOSED AND THRONE THOSE WHO EXPERIENCE REFRACTARY DISEASE. IN BOTH AREAS THE LIMITATION ARE RESOURCES. IN THE RELAPSE POPULATION, WE HAVE FAR MORE CHILDREN AND FAMILIES SEEKING INNOVATIVE THERAPIES AND CLINICAL TRIALS THAN CLINICAL TRIALS. >> SO THE REPORT SAID 4000 IN THE COG STUDY SO YOU'RE SAYING 2000 IN OTHER STUDIES. IS THAT THERAPEUTIC TRIALS OR ALSO INCLUDING BIOLOGY TRIALS OR THERAPEUTIC TRIALS? >> I DON'T WANT TO GET THE NUMBERS WRONG AND I CAN GET YOU THE RIGHT NUMBERS. BUT MOST OF THE TIME WE ARE TALKING ABOUT ON THERAPEUTIC TRIALS. AND I DON'T THINK IT IS 2000. BUT IT IS A HIGHER NUMBER BUT THERE ARE TWO GROUPS. NEWLY DIAGNOSED PATIENCE AND WE HAVE CHILDREN ON CLINICAL TRIALS WHO ARE NOT NEWLY DIAGNOSED. WE CAN GET YOU THE DATA FOR COG. THAT IS EASY. SO THE DENOMINATOR NEWLY DIAGNOSED OR THOSE ON TREATMENT? THERE ARE 14,000 NEWLY DIAGNOSED AND 30,000 KIDS ON TREATMENT. >> AND RICHARD AND I WERE TALKING ABOUT THIS EARLIER. WE SHOULD BRING CLARITY SO WE ARE ALL ON THE SAME SET OF NUMBERS. WE CAN WORK WITH NCI TO TRY TO DO THAT. AT THE END OF THE DAY, THEY WILL BE ESTIMATES BUT WE THINK THEY WILL BE GOOD ESTIMATES SO THERE WILL BE FLUCTUATIONS YEAR TO YEAR AS THE STUDY CLOSES AND SO FORTH. AND I KNOW THE ADVOCATES AT THE OTHER END OF THE TABLE KNOW THIS. WHATEVER NUMBER WE ARE TALKING ABOUT, AT LEAST THE ORDER OF MAGNITUDES ARE MORE HIGHER THAN PARTICIPATION OF ADULTS. THAT ADDS TO THE CONFUSION. >> THANK YOU. >> SUSAN, YOU ASKED AN INITIAL? >> A RELATED QUESTION. DO YOU NONACADEMIC GROUPS LIKE U.S. ONCOLOGY DO RESEARCH IN PEDIATRICS? >> WHAT IS EF DEPUTY TO ME IS THOSE OFS YOU WHO HAVE BEEN AFFECTED BY PARENTS OR GRANDPARENTS, THE BEST ADVOCATES TO PRESENT THE STORY. HOWEVER, WHAT IS ALSO CLEAR TO ME IS THAT PEOPLE LIKE MYSELF, I WON'T PRETEND TO SAY I UNDERSTOOD HALF OF WHAT WAS SAID TODAY. WHAT I WOULD SUGGEST IS THAT WE GET TALKING POINTS FOR PEOPLE LIKE ME IN SUPPORT OF THE CREATING HOPE ACT. I MET WITH SEVERAL NEW JERSEY CONGRESSMEN AND GOT THEM TO SUPPORT IT BECAUSE THAT WAS AN EASY SELL. MY GRANDSON HAD CANCER. I WAS ABLE TO TALK THE TALK. AFTER HEARING TODAY, FROM ALL THE DOCTORS AND THE MEDICAL, I'M NOT COMFORTABLE GOING INTO THE LEGISLATORS AND MAKING THE STRONGEST PITCH POSSIBLE. SO WHAT I WOULD SUGGEST IS THAT TALKING POINTS BE GIVEN TO THOSE OF US THAT WANT TO GET INVOLVED WITH OUR LEGISLATORS SO THAT WE CANNOT ONLY TELL OUR PERSONAL STORIES BUT ALSO TALK ABOUT THE STATISTICS AND THE NEED IN A MEANINGFUL WAY. >> THANK YOU. MICHELLE? >> SO UNRELATED QUESTION. STRUCK BY THIS HIGH LEVEL OF RECURRENT DISEASE OR ATTRIBUTED TO THE TREATMENT. HAVE YOU BEEN ABLE TO TEASE OUT HOW MUCH IS DUE TO TOXICITY AS A THERAPY VERSUS DUE TO SOME OTHER UNDERLYING PROBLEM THAT THE CHILDREN WOULD BE HAVING LIKE DNA REPAIR SYSTEM? >> YES. THIS IS SOMETHING THAT HAS BEEN STUDIED VERY SYSTEMATICALLY AND LODGITUDEINALLY FOR 30 YEARS. AND I THINK THERE IS NO QUESTION THAT MOST TOXICITIES ARE LATE EFFECTS OF THERAPY. THE OVERWHELMING MAJORITY OF THEM THAT ARE TRULY DEBILITATING ARE RELATED TO RADIATION THERAPY. AND PARTICULARLY COGNITIVE DYSFUNCTION AND CHILDREN WITH LEUKEMIA. AND WE HAVE LEARNED A GREAT DEAL FROM THE LONGITUDINAL INVESTIGATIONS BY REDUCING THEY WERE SPEC ELIMINATING SOME THERAPIES THAT WE KNOW ARE TOXIC AND MAINTAIN THE SAME OR IMPROVED LEVELS. SO WHETHER OR NOT THERE MIGHT ALSO BE UNDERLYING -- WE KNOW THERE ARE SOME CHILDREN WITH GENETIC DEFECTS OF DNA REPAIR. WE GENERALLY ARE ARE MORE AT RISK FOR DEVELOPING CANCER TO BEGIN WITH. AND FREQUENTLY THEY DON'T DO VERY WELL. SO STUDYING LATE EFFECTS IS PROBABLY NOT SOMETHING TERRIBLY FEASIBLE. BUT JUST LOOKING AT THE CHANGE IN THE TOXICITIES THAT WE SEE BY ELIMINATING CERTAIN THERAPIES, I THINK WE HAVE MORE THAN A SUSPICION OF WHAT THAT IS. >> JUST THE REASON YOU'RE STRUCK WITH THE HOW MUCH LONG TERM TOXICITIES WE SEE IS BECAUSE WE HAVE MANY MORE LONG TERM SURVIVORS. AND THEY SURVIVED LONGER, RIGHT? SO WHEN YOU CURE A KID WITH TIMOR AT AGE TWO, AND THEY GROW UP BECAUSE WE CURE THEM, THEN YOU'RE FOLLOWING AND YOU SEE THE TOXICITIES THAT TAKE 30 YEARS TO MANIFEST THEMSELVES AND WE DON'T SEE THAT IN MOST ADULT CANCERS. >> OTHER QUESTIONS? >> JUST FOR CLARIFICATION. GO TO THE NCI WEBSITE WHEN YOU WANT TO GET INFORMATION. WE HAVE -- IT SAYS THAT 60% OF CHILDREN UNDER THE AGE OF 15 ARE ON CLINICAL TRIALS AND 2% OF PATIENTS BETWEEN 20-39 YEARS OF AGE. >> THAT'S SO RUDE TO BRING FACTS TO THE TABLE. >> OTHER QUESTIONS AND THOUGHTS? THEN I'LL OFFICIALLY DECLARE A BREAK AND WE'LL COME BACK BY 3 CHILDREN 30 AND WE'LL COME BACK -- WE'LL COME BACK AT 3:30 AND WE'LL COME BACK TO NEXT STEPS. WHAT I'D LIKE TO, OVER THE NEXT 20 MINUTES OR SO, IS BEGIN TO GET A HANDLE ON WHAT MAKES SENSE AS NEXT STEPS FOR THE DCLG AND I THINK IT IS IMPORTANT TO COME BACK TO THE FACT THAT THE DCLG IS AN AGGREGATION, A GROUP OF ADVOCACY ORGANIZATIONS WHO COME TOGETHER TO LEARN AND TO PROVIDE FEEDBACK AND ADVISE AND EXERCISE OUR ROLE AS ADVOCATES LIKE THE ONES WE SAW IN THE ROOM TODAY PRESENTING. TO SOME DEGREE, IT'S A GREAT DEAL OF POWER BUT ALSO -- YES, ANDREA? >> DO YOU WANT TO KNOW NEXT STEPS IN REGARDS TO PEDIATRICS? >> THIS IS DESIGNED TO BE NEXT STEPS OUT OF TODAY'S MEETING. NEXT STEPS FOR THE DCLG A MONUMENTAL TOPIC THAT WILL TAKE YEARS. [ LAUGHS ] THAROBABLY IS A MEETING WE WOULD HAVE AT THE BAR. >> YOU'RE RECORDED. >> I THINK THERE WERE A COUPLE OF THINGS WE TALKED ABOUT EVEN AT THE BEGINNING OF THE MEETING BUT HAVE BECOME MORE APPARENT THAT IT WOULD BE GOOD TO HAVE THE REPRESENTATION AT LEAST ONE FOCUSED PEDIATRIC ADVOCACY GROUP IN THE MIX SO THAT EVERY TIME WE HAVE A DCLG MEETING, THERE IS SOMEBODY THERE HOLDING OUR FEET TO THE FIRE TO MAKE SURE WE ARE COGNIZANT OF THE PEDIATRIC ASPECTS OF THAT. AND WE WILL DEFINITELY MAKE THAT HAPPEN. I SAY WE, BECAUSE I'M GOING TO FLY BACK TO NORTH CAROLINA AND LEAVE IT UP TO MY CAPABLE PARTNERS HERE TO MAKE THAT HAPPEN. BUT THE GOAL REALLY WILL BE TO TRY AND STRENGTHEN OUR KNOWLEDGE AND PARTICIPATION WITHIN THE DCLG AS ADVISORY GROUP. THE MEMBERSHIP ON THIS GROUP EBBS AND FLOWS BECAUSE SOMETIMES WE HAVE OVER REPRESENTATION OF SOME THINGS AND OTHERS. IT'S NOT LIKE IT IS INTENDED TO BE LIMITED TO ONE BUT IT DOESN'T WANT TO BE THE PEDIATRIC ADVISORY GROUP. WE'LL FIND A HAPPY MEDIUM TO MAKE SURE THE VOICES ARE REPRESENTED AT THE MEETING. SECONDARILY, YOU'RE PART OF THE COMMUNITY. I MEAN, YOU KNOW WHO WE ARE AND KNOW WHO THE FOLKS ARE AND AT THE OFFICE ADVOCACY RELATIONS, YOU MET SOME OF THE MOST SENIOR OFFICERS OF NCI HERE TODAY. SADLY JOHN IS LEAVING. I HEAR SADNESS NEXT TO ME. BUT, THIS IS NOW A GROUP OF FRIENDS. THIS IS A TEAM SPORT ADVOCACY FOR CANCER TREATMENTS AND CURES AND WHAT WE HAVE DONE IS EXPAND OUR TEAM TODAY FROM ALL ASPECTS AND IT HAS BEEN A PLEASURE TO HAVE EVERYBODY HERE FOR THAT VERY REASON. WE KNOW HOW TO CALL EACH OTHER AND HOW TO USE OUR E-MAILS AND TO TAKE ADVANTAGE OF THIS. I WAS COMMENTING TO VICKI, THIS SHOULD HAVE BEEN THE BEST AD EVER FOR HER GROUP. THAT IF WHAT WE WANT IS COMMUNICATION VEHICLES, WE WERE PRESENTED WITH ONE WHERE THERE IS A COORDINATING GROUP FOR PEOPLE INTERESTED IN PEDIATRIC CANCER ADVOCACY. IT WASN'T MY INTENTION WHEN WE TARTED -- STARTED THIS MEETING BUT IT WAS A GREAT HAPPY OUTCOME FROM THIS KIND OF MEETING THAT WE GAINED RESOURCES JUST BY GETTING TOGETHER. I THINK ALSO THIS MEETING SHOULDN'T BE CONSIDERED TO BE THE END OF THIS DISCUSSION. IT SHOULD BE THE BEGINNING OF THIS DISCUSSION. IT GOT TRIGGERED BECAUSE DAVID WAS WORKING ON THESE SAME ISSUES IN BRAIN CANCER AND IT SEEMED SO RELEVANT TO MOVE IT TO ANOTHER LEVEL WHERE WE BROADENED THE DISCUSSION. FOCUSED. -- TAKE ADVANTAGE OF THAT. WE HAD SOME DISCUSSIONS, THANK YOU, ABOUT VAGUERIES AND NUMBERS AND NUMBERS ALWAYS MOVE IN A PLACE LIKE THIS WHERE THERE IS NOT ONE CONTROL POINT BUT NCI IS A GOOD SOURCE FOR A LOT OF THESE NUMBERS AND WHAT WOULD BEHOOVE US IN OUR DISCUSSIONS IS TO HAVE NUMBERS THAT ARE NARROWED DOWN. AS I SAID, JOHN WAS SO RUDE HE LOOKED UP THE NUMBER AND CONFOUNDED US WITH FACTS. BUT, I WOULD LIKE TO MAKE SURE THOSE NUMBERS ARE LOOKED AT CAREFULLY AND SCRUBBED AND WE HAVE GOOD NUMBERS ON THE NCI WEBSITE THAT WE CAN ALL USE AS A GOOD REFERENCE POINT FOR OUR DISCUSSIONS. I DON'T THAN IT WILL EVER BE DEFINITIVE. I FACE THAT IN BRAIN CANCER. THERE ARE JUST NOT DEFINITIVE NUMBERS FOR SOME OF THE THINGS WE LOOK AT. IF WE COULD NARROW THE GAP AND BEGIN TO HAVE COMMON VOCABULARY THAT SAY GREAT HELP. SO THOSE ARE THINGS I STARTED OFF WITH. I THINK AMY THOUGHT A BIT ABOUT THIS AND WE'LL HAVE TO PONDER FROM AN NCI STANDPOINT WHAT THE NEXT MEETINGS MAY BE OR ACTION STEPS FROM THAT, BUT WHY DON'T YOU TALK TO YOUR THINKING HERE. >> SURE. I'M HAPPY TO AND I DON'T HAVE ANYTHING HARD AND FAST BUT BEFORE I DO TALK A LITTLE BIT, IS THERE ANYONE AROUND THE TABLE WHO HAS THOUGHTS OF THINGS THEY WOULD LIKE TO EXPLORE FURTHER OR WHETHER IT BE A TOPIC OR AN ISSUE OR JUST ANYTHING? I THINK WE COVERED A LOT. IT WAS A VERY CONTENT-RICH DAY. AND I WOULD LOVE TO HEAR WHAT RESONATES WITH YOU. >> EVERYTHING RESONATED. IT WAS A REALLY EXCELLENT MEETING. ONE THING THAT MAY BE HELPFUL TOO, WE HAVE GOT NOW GREAT INFORMATION ON SEVERAL OF THESE ORGANIZATIONS THAT ARE REAL ACTIVE IN THE PEDIATRIC SPACE. WHAT ARE SOME OF THE OTHER ORGANIZATIONS LIKE YOU OR OTHER ORGANIZATIONS THAT ARE INVOLVED IN PEDIATRICS WITH AT LEAST SOME OF WHAT WE DO WITH PEDIATRIC CANCER THAT MIGHT BE HELPFUL FOR US TO RECOGNIZE AS A RESOURCE? >> I'LL JUST ADD THAT I HAVE BEEN HERE THREE PLUS YEARS AND THIS IS THE MOST INSPIRING AND INFORMATIVE MEETING I HAVE BEEN TO. I WAS ANEWED HAVE THE PEOPLE WE HAD FROM THE FDA, TOP SCIENTISTS AT THE NCI, TOP EXTRAMURAL RESEARCHERS, THE ENTIRE COMMUNITY. TO HAVE EVERYONE AROUND AM IN THE AUDIENCE HERE TODAY AND TO HEAR FROM ALL OF YOU AND IT IS JUST FANTASTIC. I THINK THE ONE COMPONENT I FEEL LIKE I'M MISSING IS INDUSTRY. TO SOME DEGREE IT WOULD BE INTERESTING TO HAVE SOMEONE FROM INDUSTRY COME IN AND MAYBE CONTINUE THE DISCUSSION WITH THEM A LITTLE BIT. I MEAN, I'M SURE MUCH MORE AWARE THAN I WAS COMING INTO THIS ROOM JUST ABOUT THE CHALLENGES WITH REGARDS TO THE PEDIATRIC CANCER. >> I WILL SAY THAT WE TRIED RECOGNIZING WE PUT THIS TOGETHER ON RELATIVELY SHORT NOTICE BECAUSE OF THE URGENCY OF THE ISSUE, THE WAY IT COME UP. AND PHARMA MOVES IN GLACIAL PACES SOMETIMES PROBABLY BECAUSE OUR CALENDARS ARE BOOKED TWO YEARS AHEAD OF TIME. I THINK IF WE PUT OUR MINDS TO IT AND HAVE THE RIGHT AMOUNT OF LEAD TIME WE COULD CONVENE A SMALL MEETING WHERE WE HAD THE ABILITY TO GET-TOGETHER WITH THE RIGHT REPS FROM INDUSTRY. IT DIDN'T WORK FOR THIS. AND WE HAD ENOUGH CONTENT BUT I THINK THAT IS A LOGICAL NEXT STEP. MOST DRUGS IN MOST CANCERS ARE DEVELOPED THROUGH INDUSTRIAL PATHWAYS. THAT HASN'T BEEN TRUE HERE. AND IT WOULD BE GOOD IF WE COULD DO THAT. >> DEFINITELY NOT A CRITICISM. JUST A FOLLOW-UP TO THIS MEETING. >> IN THE INTERIM, PHARMA DID -- THERE WERE THREE PRESENTATIONS ON THE ONCOLOGY ADVISORY COMMITTEE YOU'RE ON, NANCY, BACK IN NOVEMBER. NOVARTIS, AMGEN AND BRISTOL MIRE SQUIBB GAVE PRESENTATIONS AND I BELIEVE THAT I ARE IN THE FDA WEBSITE. VERY INTERESTING. >> THIS IS MY FIRST EXPOSURE TO CANCERS. BUT FROM THE CYSTIC FIBROSIS CASE STUDY AND THE DRUG THEY JUST GOT APPROVED BECAUSE IT IS A SIMILAR SIZE POPULATION. ALSO ORPHANED DRUGS WITHOUT INDUSTRY PARTICIPATION BECAUSE OF LACK OF SIGNS IN THE MARKET. I'M WONDERING IF THERE IS ANYTHING YOU LEARNED FROM CYSTIC FIBROSIS OR NOT. >> AND OUR COMMUNITY SPENT QUITE A BIT OF TIME WATCHING THEM AND BEING JEALOUS OF THEM. AN AMAZING MODEL. I THINK ABOUT 80,000 KIDS HAVE CYSTIC FIBROSIS. -- RECENTLY APPROVED HAS INDICATED FOR 15% OF THE POPULATION. ONE OF THE INTERESTING THINGS ABOUT THE CYSTIC FIBROSIS FOUNDATION IS IS IT JUST ONE INDICATION. THERE ARE OVER 100 PEDIATRIC CANCERS. THAT IS VERY, VERY DIFFERENT PIECE OF THE MODEL. THEY RAISE OVER 100 MILLION DOLLARS A YEAR AND PUT IT ALL INTO DRUG DEVELOPMENT. COFUND COMPANIES AND SO IT IS REALLY INTERESTING MODEL. RIGHT NOW FUNDING IN OUR COMMUNITY IS VERY FRACTURED AND WE HAVE MANY INSTITUTIONS AND NONFLOORS RAISE SMALL AMOUNTS OF MONEY AND ST. JUDE WHICH IS THE ELEPHANT NOT IN THE ROOM RAISING 800 MILLION DOLLARS LAST YEAR. UNFORTUNATELY, IT'S NOT A MODEL THAT MATCHES OUR COMMUNITY. >> IN ADDITION TO LEARNING HOW TO USE THIS, LET ME SHARE WITH YOU SOMETHING ELSE THAT I GOT PERSONALLY OUT OF THIS MEETING AND I APOLOGIZE TO KELLIE, HOLLY AND AMY FOR THE E-MAILS THAT I HAD WRITTEN OVER THE LAST FEW YEARS AS TO MY ANGER THAT ONLY 3.9% OF FUNDS ALLOCATED BY NATIONAL CANCER INSTITUTE GO INTO PEDIATRIC CANCER. WHEN I LEARNED FROM TODAY IS WE ARE NOT ADVERSARIES. WE ARE PARTNERS IN THIS AND WE, AS PEDIATRIC CANCER COMMUNITY HAVE AN OBLIGATION TO MAKE OUR CASE NOT ONLY TO THE LEGISLATORS BUT ALSO TO NCI AND TRY TO FIND SCIENTISTS THAT WILL SEEK GRANTS FROM THE NCI AND THEN IF WE CAN INCREASE THE PIE, AT LEAST WE HAVE A PARTNER WITH US. I'M CONVINCED OF THAT, IN TRYING TO INCREASE 3.9. SO I AGAIN APOLOGIZE TO KELLIE, HOLLY AND AMY FOR MY E-MAILS. [ LAUGHS ] >> ONE OF THE THINGS I FOUND MOST INTERESTING AND WE TALKED ABOUT IT AND THEN VEERED AWAY FROM IT, FAIRLY QUICKLY, BUT I THINK THERE ARE SOME RESOURCES IN THE ROOM THAT COULD HELP US ALL WAS, I USED TO BE LEGAL COUNSEL TO A LARGE MEDICAL CENTER AND AS SUCH, I SAT IN THE IRBs. AND WHEN YOU SIT IN THE IRB, IT IS OPAQUE NOBODY KNOWS WHERE IT IS, WHEN IT IS, YOU DON'T KNOW THE REPS ON IT. OFTEN IT IS JUST STAFF REPRESENTING THE PROTOCOL WITH THE INVESTIGATOR SITTING THERE QUIETLY. EVERYBODY IS FROM DIVERSE PARTS FROM THE UNIVERSITY MEDICAL CENTER SO THEY DON'T KNOW THE FIELD YOU'RE TALKING ABOUT WELL. BUT THEY ARE PERFECTLY WILLING TOO PINE ON RISK AND THEN HAVE YOU DESIGNATED COMMUNITY MEMBERS, LAWYERS AND OTHERS WHO HEARING THE WORD, RISK, SPIRAL INTO THIS INCREDIBLE RISK STRAITS SPHERE. THERE IS NOBODY TO COUNTER THAT IN MOST IRBs. AND AS WE TALKED ABOUT, YOU SAID YOU WENT INTO THE IRB WITH YOUR INVESTIGATED PARTNER WITH THE DOC WHO WANTED TO DO THIS PROTOCOL. I DON'T THINK IN MY ENTIRE TIME ATTENDING IRB MEETINGS, A SINGLE PATIENT ADVOCATE CAME TO THE IRB. AND I WOULD LOVE TO HAVE US LEARN HOW TO DO THAT A LITTLE MORE EFFECTIVELY. WE LOOKED AT THE THINGS THAT ARE BARRIERS TODAY AND ACTED AS IF THEY ARE REGULATORY BARRIERS. AND IN MANY CASES, THEY ARE SELF-INFLICTED WOUNDS BY THE MEDICAL CENTERS THAT ARE INVOLVED, THAT THEY DETERMINE YOUR RISK FOR YOU AND ONE OF MY GREATEST FRUSTRATIONS WORKING WITH CANCER PATIENTS AND CANCER PARENTS IS WHO ARE THEY TO DETERMINE THE LEVEL OF RISK THAT I, AS A CANCER PATIENT OR THAT WE AS A CANCER FAMILY, ARE WILLING TO TOLERATE WITHIN BOUNDS? AND THAT IS A DIALOGUE THAT WE DIDN'T HAVE TODAY BUT IT CAME UP A COUPLE OF TIMES AND I WOULD LOVE TO JUST ENCOURAGE PEOPLE TO THINK ABOUT WHEN THEY ARE LOOKING AT THESE EXPERIMENTAL TREATMENTS AND LOOKING AT THE PROTOCOLS AND THEIR MEDICAL CENTER, THAT WE ASSERT OURSELVES A LITTLE MORE AS ADVOCATES TO GET IN THAT ROOM. CAN YOU EXPLAIN YOUR EXPERIENCE A LITTLE BIT WITH THAT? >> SURE. I GET WITH RESPECT TO A PROGRAM WE HAVE AT KIDS VERSUS CANCER WHERE WE COLLECT OR FACILITATE THE DONATION OF PEDIATRICS POST MORTEM AUTOPSY TISSUE FOR BRAIN CANCER TO RESEARCH RESEARCH. AND THE I. -- THE IRB DOESN'T HAVE JURISDICTION BECAUSE IT'S NOT A LIVE HUMAN SUBJECT. WE DETERMINED THAT AND SAID IT. HOWEVER, WE FOUND THAT TWO HOSPITALS WORKING WITH IN PARTICULAR WERE LIMITING THE PHYSICIAN'S ABILITY TO COOPERATE WITH US IN THIS PROGRAM SO LITERALLY I CALLED UP THE DIRECTOR OF THE IRB AND I SAID, COULD I PLEASE COME IN AND TALK TO YOU? AND YOU JUST GO IN AND TALK ABOUT WHO YOU ARE AND WHAT YOUR EXPERIENCE IS AND EVERYONE HEARS AN ADVOCATE KNOW THAT IS WHEN YOU SHOW UP YOU'RE 80% OF THE WAY THERE. RIGHT? SO MAYBE WHAT WE NEED TO DO IS, LET THE CLINICIANS WE WORK WITH KNOW THAT WE ARE RESOURCE. DO YOU HAVE A COMMENT? >> [ OFF MIC ] >> PEDIATRIC CANCER CLINICAL TRIALS ARE UNDER CENTRAL IRB. THEY ARE LIMITOD WHAT THEY CAN DO IN ORDER TO CHANGE ANY PROTOCOL. BECAUSE I USED TO SIT ON CHILDREN'S INITIAL MEDICAL CENTER IRB AND BEFORE THE CENTRAL IRB, WE HAD A LOT MORE LEEWAY TO DO THINGS AND I CAME OFF THE IRB WHEN IT WENT TO CENTRAL BECAUSE I COULDN'T DO ANYTHING. SO I THINK THAT YOU HAVE TO LOOK AT THAT STRUCTURE AND THEN WORK WITHIN IT. >> SO RUTH, I THINK THAT THE STEPS OF THAT WOULD BE TAKEN THE COG PUTTING TOGETHER, FOR EXAMPLE PERMIT BIOPSIES IN CERTAIN INSTANCES AND THEN IF CHILDREN'S ONCOLOGY GROUP ELECTED TO DO THAT, MAYBE COG COULD IDENTIFY A TEAM OF PARENT ADVOCATES WHO FAN OUT ACROSS THE COUNTRY AND JUST GO TALK TO THE IRBs. YOU WOULD HAVE DIFFERENT PEOPLE IN EACH STATE PERHAPS WHO WOULD TAKE RESPONSIBILITY FOR JUST ENSURING THAT IRBs ARE HOSPITALS IN THEIR REGION AND FELT COMFORTABLE PURSUING THAT DIRECTION. >> OTHER THOUGHTS? BEFORE WE LOSE YOU, PLEASE MAKE SURE THAT AMY AND I HAVE ALL YOUR CONTACT INFO. MY SENSE IS, THIS IS A COLLECTION POINT FOR A GROWING COMMUNITY. AND THAT IT WILL BE NICER IF IT IS EASY FOR ALL OF US TO STAY IN TOUCH, IF WE CAN DEVELOP SOME NEXT STEPS THAT BRING US BACK TOGETHER. IT WOULD BE GREAT. >> ABSOLUTELY AND JUST TO FOLLOW-UP ON THAT, I THINK WE HAD A VERY ROBUST DISCUSSION TODAY AND IT IS A TESTAMENT TO HOW MANY DIFFERENT ORGANIZATIONS AND PEOPLE AND PLAYERS ARE PURSUING THIS. I THINK WE HAVE A LOT OF MOMENTUM THAT HAS BEEN GENERATED BY THE PARTICIPANTS AND PANELISTS. AND THIS IS JUST A POINT IN TIME IN THIS DISCUSSION, A DISCUSSION THAT ALL OF YOU AROUND THE TABLE AND IN THIS ROOM HAVE BEEN HAVING FOR YEARS. I THINK IT IS A NEWER DISCUSSION FOR SOME MEMBERS ON THE DCLG BUT I THINK THE DISCUSSION, I KNOW THE DISCUSSION WILL CONTINUE ON FROM HERE. AND WE WANT TO BE A PART OF THAT AND BE A THRESHOLD FOR THIS DISCUSSION GOING FORWARD. OUR OFFICE IS WORKING WITH OUR LEADERSHIP WITHIN THE INSTITUTE AS YOU SAW, BY THE PEOPLE AROUND THE TABLE AND ACROSS HHS AGENCIES, AS YOU SAW BY THE PEOPLE AROUND THE TABLE. AND ALSO THE WHITE HOUSE WHO IS IN CONTACT THROUGH THE OFFICE OF PUBLIC ENGAGEMENT WITH A LOT OF ADVOCACY CANCER ORGANIZATIONS, SO I KNOW THAT THEY ARE AWARE OF THIS MEETING. THEY ARE AWARE OF ITS IMPORTANCE. THEY HAVE REACHED OUT TO US BECAUSE THEY ARE SO INTERESTED AND I KNOW THAT THOSE DISCUSSIONS WILL CONTINUE. SO I REALLY WANT TO MAKE SURE THAT WE KEEP THIS GROUP TOGETHER SO THAT I CAN COOP YOU INFORMED AS THESE THINGS EVOLVE AND AS THINGS TAKE SHAPE OUT OF IT. >> I THOUGHT TODAY WAS TREMENDOUSLY INFORMATIVE AND I DON'T THINK WE COULD HAVE HAD A MORE WELL COMPOSED QUESTION THAN WHAT CAVED SAID, THE SOUNDBITE OF THE DAY AND ASKED, WHAT IS THE BIGGEST BANG FOR OUR BUCK? I WOULD SAY, MAKE THOSE OUR NEXT STEPS AND FIND OUT WHO WE SHOULD POSE THOSE QUESTIONS TO AND GET THOSE ANSWERS AND START TAKING ACTION AND WHAT YOU SAID ABOUT HAVING TALKING POINTS FOR PEOPLE TO BE ABLE TO SPEAK WITH OUR LEGISLATORS. THOSE ARE SOME THINGS TO THINK ABOUT. >> I'M HOPING TO FOLLOW IN THE STREAM OF DAVID'S GOOD WORK HE IS DOING FOR NBTS ON THIS AND DON'T YOU HAVE FUTURE MEETINGS COMING UP WHERE YOU'RE FOCUSIN ON SOME OF THIS? I'M HOPING YOU WILL KEEP US INFORMED IS WHAT I'M REALLY SAYING. >> SURE. AND THEN WE ARE PRETTY NEW AT THE PEDIATRIC ARENA IN TERMS OF POLICY AND SOME OF THESE ISSUES. WE HAVE BEEN A FUNDER IN THIS ARENA FOR A FEW MORE YEARS BUT I KNOW WE HAVE JUST -- OUR BOARD SAID DO MORE. SO, STAFF IS DOING MORE AND THEN WE HAVE A MEETING COMING UP ON MARCH 13, A FOLLOW-UP MEETING, BECAUSE ABOUT A YEAR AGO WE WERE JUST ASKING PEDIATRIC BRAIN TUMOR RESEARCHERS, WHAT DO YOU SEE AS BIG BARRIERS? AND A LOT OF THEM SAID IT'S THE DIFFICULTY IN GETTING DRUGS FROM PHARMACEUTICAL COMPANIES, BOTH FOR PRECLINICAL RESEARCH AND THEN FOR CLINICAL TRIALS. AND SO, WE HAVE BEEN HOSTING ONE MEETING ON THAT BUT OTHER GROUPS DOING OTHER MEETING IN MARCH AND ANYBODY IS WELCOME BUT TO TRY TO DIG DEEP OR SOME OF THESE IMPEDIMENTS TO PEDIATRIC BRAIN TUMOR CANCER RESEARCH, THAT ARE ALL LIKE WE HEARD TODAY, INTERCONNECTED BUT AT THE END OF THE DAY, TRYING TO MAKE SURE THAT RESEARCHERS GET THE DRUGS THEY NEED, PHARMACEUTICAL COMPANIES FEEL LESS RISK AND ARE THEREFORE IN SEPTEMBERVISED. THINGS RESULT IN HOPEFULLY CLEARER RULES OF THE ROAD BUT -- INCENTIVIZED. WE ARE LOOKING FOR THE RIGHT GPS LIKE EVERYBODY ELSE. STILL HAVEN'T FOUND OUR GAM IN OR TOM TOM YET. BUT, THAT IS WHAT WE ARE IN SEARCH FOR. MEETINGS LIKE TODAY HELPS AND HAVING NANCY HERE HELPS A LOT BECAUSE THERE IS A WHOLE, AND JOHN YOU ALLUDED. WE DIDN'T HAVE INDUSTRY HERE TODAY BUT OUR ASSESSMENT AND OUR NAIVE ASSESSMENT OF MY ORGANIZATION HAS DONE, THERE IS BIG BUSINESS MODEL PROBLEMS IN PEDIATRIC CANCER THAT ARE DIFFERENT FROM THE SCIENTIFIC PROBLEMS OR AT LEAST RELATED AND SO HOW DOE WE PUT IT ALL TOGETHER? I THINK NANCY YOUR FOCUS, A LOT OF EXPERIENCE IS WHAT ARE THE BUSINESS MODEL PROBLEMS THAT INTERSECT WITH THE SCIENTIFIC AND CLINICAL PROBLEMS. SO I COME AWAY WISHING WE HAD ANOTHER MEETING BUT WITH THE CEOs OF SEVERAL PHARMACEUTICAL COMPANIES SO WE CAN ASK THEM NOT JUST SCIENTIFIC QUESTIONS ABOUT THESE BUT WHAT IS YOUR ASSESSMENT OF HOW DO WE MAKE THIS A BUSINESS SPACE YOU WANT TO GET MORE INVOLVED IN? THAT'S DREAMING. >> UNFORTUNATELY, THEY WON'T COME AND -- >> I GO BACK TO MY PARABLE. >> SPENDING 12 YEARS IN INDUSTRY, WHEN SUSAN CALLED ME OVER A CHRISTMAS BREAK AND SAID LINDA, WE HAVE A PROBLEM, CAN YOU HELP ME? I WAS MORE RECEPTIVE IN HELPING HER AND I THINK WE DID THAT. >> I'M GOING TO TAKE GREAT PRIDE IN DECLARING VICTORY AND SAYING IT IS NOW 4:00. WE HAD A WONDERFUL DAY. I MADE MANY NEW FRIENDED AND WE ARE GOING TO ADJOURN ON TIME. SO THANK YOU ALL FOR GREAT EFFORTS. [ APPLAUSE ] >> AGAIN, THANK YOU VERY MUCH. THERE IS A LOT THAT WEPT INTO THIS BOTH TODAY AND THEN THE WEEKS LEADING UP TO IT AND EVERYONE IN THE ROOM PLAYED A PART SO I THANK YOU VERY MUCH ESPECIALLY A LOT OF THE ADVOCACY STAFF. I REALLY APPRECIATE ALL THAT YOU DID. THANK YOU.