>> I WANT TO FIRST WELCOME EVERYONE TO THE 25th MEETING OF CLINICAL TRIALS AND TRANSLATIONAL RESEARCH ADVISORY COMMITTEE. NANCY MENTIONED WE SHOULD HAVE SOME TYPE OF CELEBRATION BUT BEING GOOD APPROVAL STEWARDS OF OUR RESOURCES WE'RE JUST GOING TO MOVE INTO OUR WORK TODAY. SO FIRST OF ALL EVEN THOUGH SOME OF THESE FOLKS ARE NOT HERE YET, WELCOME A NUMBER OF AD HOC MEMBERS THAT ARE GOING THROUGH THE COMMITTEE, THEY ARE GOING THROUGH THE APPROVAL PROCESS NOW. THEY INCLUDE DAVID AARONS AARONS WHO IS WITH US TODAY WHO IS DIRECTOR OF PUBLIC POLICY AT THE NATION BRAIN TUMOR SOCIETY, SO WELCOME. DR. MICHAEL LABLANC, I DON'T KNOW IF HE'S HERE YET, BUT PROFESSOR OF BIOSTATISTICS AT UNIVERSITY OF WASHINGTON. DR. DAVID MANKOFF, PROFESSOR RADIOLOGY U PENN. AND LOU WEINER AND PROFESSOR OF THE GEORGETOWN UNIVERSITY, DIRECTOR OF THE CANCER CENTER AT GEORGE TOWN. AND IF PEOPLE ARE INTERESTED I HAVE MORE DETAILED BIOGRAPHY OF ALL THE NEW MEMBERS IF PEOPLE WANT TO LOOK AT THAT. I WILL READ TWO STATEMENTS THAT ARE ESSENTIAL BEFORE WE GET GOING. FIRST OF ALL THE OPENING STATEMENT, AS COMMITTEE MEMBERS YOU MUST ABSENT YOURSELF DURING SPECIFIC DISCUSSIONS WHENEVER YOUR PARTICIPATION ON A PARTICULAR PRODUCT PROGRAM OR OTHER SPECIFIC MATTER WOULD CONSITUTE A CONFLICT OF INTEREST OR CREATE THE APPEARANCE OF ONE. IT'S INCUP BENT UPON YOU TO ADVICE THE SECRETARY DR. PRENTVILLE AND ABSTAIN IN ANY DISCUSSION IN LIGHT OF THE CURRENT MATTER. IN LIGHT OF THE CURRENT STANDING OF SPECIAL GOVERNMENT EMPLOYEES WHICH INCLUDE ALL MEMBERS OF THE COMMITTEE WE MUST VOLUNTEERS UNSUPPORTED TARLY ASK TO YOU ABNORMALITIES SEBT YOURSELF DURING ANY AND ALL MATTERS THAT COULD IMPACT THE STATUS OF THOSE HOLDINGS. WE TRUST YOUR JUDGMENTS IN THESE INSTANCES. BY LAW A QUORUM IS REQUIRED FOR EACH INSTANCE IN WHICH IT OCCURS IN AN OPEN SESSION. WE HAVE A QUORUM. NEW MEMBERS WHO ARE NOTES MEMBER OF ANOTHER NCI ADVISORY BOARD ARE NOT VOTING UNTIL THAT I HAVE BEEN CLEARED BY THE NCI ETHICS OFFICE AND THE OFFICE OF HUMAN RESOURCES PUBLIC COMMENT STATEMENT FOR MEMBERS OF THE STATEMENT WHO MAY WISH TO EXPRESS VIEWS DURING ANY ITEMS DISCUSSED THROUGH THE MEETING MAY DO SO BY WRITING DR. SHEILA PRENTVILLE, ANY WRITTEN STATEMENTS BY MEMBERS OF THE PUBLIC WILL RECEIVE CAREFUL CONSIDERATION. I WANT NOW TO ENTERTAIN A MOTION TO ACCEPT THE MINUTES FROM THE JULY 16th 2014 CTAC MEETING. SECOND? AND ALL IN FAVOR OF ACCEPTING THE MINUTES. ANY OPPOSE? ANY ABNORMALITIES TENSIONS? THE MINUTES ARE ACCEPTED. NEXT WE'LL MOVE TO THE UPDATE FROM DR. DOROSHOW THE DEPUTY DIRECTOR. I WANT TO POINT OUT THAT AS HE MOVES THROUGH HIS PRESENTATION AT THE END, WE WILL NEED TO ENTERTAIN A MOTION TO FORM A--I GUESS A WORKING GROUP OF CTAC WHO WILL OVERSEE THE NCI'S RESPONSE TO TO THE RECALCITRANT CANCER PLANS THAT HAVE BEEN PUT INTO PLACE, ONE FOR PANCREATIC ADENO DUCTAL CARCINOMA AND THE OTHER FOR SMALL CELL LUNG CANCER AND A REMIND TORE THE COMMITTEE THAT AT THE END OF THE COMMISSION, WE WILL NEED TO TAKE THAT UP. SO TIN THINGS OVER TO JIM AT THIS POINT. >> THANK YOU, APPRECIATE EVERYONE'S WHO HERE FOR THIS MEETING. IT'S AN IMPORTANT MEETING. I HAVE SEVERAL TOPECS TO COVER AND HOPEFULLY WE WILL DO IT IN A TIMELY, TIMELY FASHION. THE FIRST IS TO GIVE YOU AN OVERVIEW AND UPDATE ON THE RECALCITRANT CANCER ACT AND THE INITIATIVE AROUND THAT AND IN PARTICULAR AS WILL COME AT THE END OF THIS PORTION THIS MORNING TO GET YOUR ACCEPTANCE OF WORKING GROUPS TO OVERSEE THE PROGRESS THAT HAS BEEN AND WILL BE REVIEWED BY CTAC. SO JUST TO REMIND YOU ABOUT 18 MONTHS AGO CONGRESS PASSED THE CALCITRANT RESEARCH ACT WHICH CHARGED THE NCI WITH DEPRIVATIONING FRAMEWORKS FOR RESEARCH IN PANCREATIC ADENO CARC NOME NOMA AND SMALL CELL LUNG CANCER AND ONE REPORT LED BY A C IT WAS SENT TO MARCH IN AND JULY, THIS WAS A REPORT OVERSEEN BY CHARLIE AND AND BASICALLY REVIEW AND IT WILL STIR THE PURPOSE OF PROVIDING A REVIEW AND THE FRAMEWORKS AND EFFECTIVENESS OF THE RESEARCH OVER THE NEXT FIVE TO SIX YEARS ON A BI-ANNUAL BASIS, BASICALLY THE LAW STATES THAT THE NIH WILL PROVIDE CONGRESS WITH ACTIVITIES AND A SUMMARY OF THE REWARDS IN THE AREAS AND PROGRESS MADE TOWARDS. GOAL OF RECALCITRANT CANCER ACT. SO JUST TO GIVE YOU AN IDEA ABOUT OVERSIGHT, SINCE THE LAST TIME WE TALK ABOUT THE ACTUAL SPECIFICS OF THE REPORTS THAT WERE SUBMITTED IN MARCH AND JULY NCI'S DEVELOPED INTERNAL GROUPS TO BASICALLY TRACK THE PROGRESS OF THE INITIATIVE TO PUT FORTH IN THOSE COMMITTEES. ONE THING WE WILL DO TODAY IS TO TRY TO AN EXTERNAL GROUP OF STAKE OLDERS TO FOLLOW THE PROGRESS AND HELP US ASSESS WHETHER OR NOT THOSE RECOMMENDATIONS ARE BEING COMPLETED AND WILL HELP US TO REPORT BACK TO CTAC ON ANNUAL BASIS. SO JUST AS A REMINDER, WITH RESPECT TO SMALL CELL LUNG CANCER, MAJOR PARTS OF OF THAT REPORT WITHOUT GOING INTO GREAT DETAIL HAVE TO DO WITH HOW DO WE DEAL WITH THE ISSUE OF NOT HAVING THE APPROPRIATE NUMBER AND AMOUNT OF TISSUE AND CELL LINES TO UNDERSTAND THE UNIQUE BIOLOGY OF SMALL CELL LUNG CANCER. THE EFFORT IN TERMS OF SEQUENCING, SMALL CELL LUNG CANCER TO DATE AS BEEN MODEST PRIMARILY BECAUSE OF THE DIFFICULTY OF OBTAINING THE AMOUNTS OF PURIFIED MATERIAL NECESSARY FOR SEQUENCING SO ONE OF OUR GOALS HAS BEEN TO ENCOURAGE OUR COLLEAGUES IN CANCER CENTERS TO SUPPLEMENT THE MATERIALS THAT ARE AVAILABLE TO INVESTIGATORS. AND SO, MONEY'S FOR A GROUP OF ABOUT--I THINK IT'S 11 OR 12 NCOR SITES AS WELL AS WELL AS A DOZEN NCI CANCER CENTERS HAVE BEEN FORTH COMING TO TRY TO ASSIST IN THE DEVELOPMENT OF A BANK OF TISSUE THAT COULD BE PROPAGATED AS PATIENT DRIVED XENOGRAPHS FROM THE COMMUNITY. AND WE'RE MOST HOPEFUL BUT THESE MATERIALS, THOSE WILL BE FORTH COMING FROM NCOR SITE WHICH IS HAVE AN ENORMOUS PATIENT BASE AND SINCE WE'RE LOOKING PARTICULARLY FOR PATIENTS, PATIENT MATERIALS, FOR MOST TUMORS THAT ARE UNTREATED AND THEN AGAIN TO OBTAIN MATERIALS AT THE TIME OF RELAPSE, IT'S LIKELY THAT THE COMMUNITY PHYSICIANS, ORGANIZED IN THE NCOR WILL BE PROPERLY MOST HELPFUL IN THIS REGARD BUT WE'LL SEE OVER THE NEXT THREE YEARS HOW WELL WE CAN ENHANCE THE TISSUES THAT ARE AVAILABLE. IN THE SAME, AND BASICALLY THE SAME BULLET IS TO NOT ONLY OBTAIN THE TISSUES BUT THEN TO CHARACTERIZE THE GENETIC NATURE OF THOSE TISSUES, BOTH AT A GENETIC AND EPIGENETIC BASIS. WE HAVE SOME ASSURANCES FROM THE TCGA THAT RESOURCE TO DO THOSE ANALYSIS IF WE HAVE THE MATERIALS WILL BE FORTH COMING. THERE ARE ALSO OTHER EFFORTS RELATED TO DEVELOPING BETTER WAYS TO PERHAPS UNDERSTAND EARLY DIAGNOSIS AND DEVELOP SCREENING TESTS AND THE DIVISION OF CANCER PREVENTION IS ACTIVELY INVOLVED IN DEVELOPING A P. A. IN THIS AREA TO DEVELOP NEW AND MOLECULAR METHODS TO SCREEN PATIENTS AT HIGH RISK OF DEVELOPING SMALL CELL LUNG CANCER, AND FINALLY, THE DIVISION OF CANCER TREATMENT AND EVALUATION IS ALSO ENGAGED IN DEVELOPING PROGRAM ANNOUNCEMENTS TO UNDERSTAND NOT ONLY THE POTENTIALLY NEW MOLECULAR VULNERABILITY OF SMALL CELL LUNG CANCER BUT ALSO WAYS TO UNDERSTAND THE NEW APPROACHES TO THE RAPID DEVELOPMENT OF ACQUIRED RESISTANCE IN THAT DISEASE AND SO IT'S LIKELY THAT PERHAPS AT NEXT YEAR'S MEETING AT THIS TIME WE WILL HAVE THOSE P As BOTH OF THEM TO REVIEW AND SHOULD BE AT NEAR FINAL FORM OR HAVE BEEN ISSUED BY THE TIME OF OUR MEETING A YEAR FROM NOW. WITH RESPECT TO PDAC, THE RFA BETWEEN THE NCI AND NATIONAL INSTITUTE FOR DIABETES AND DIGESTIVE DISEASES AND KIDNEY DISEASES WAS ISSUED IN OCTOBER. I CAN'T TELL YOU, I DON'T KNOW HOW MANY APPLICATION VS COME BACK IN, BUT WE'LL KEEP YOU UP TO DATE WITH THAT. I THINK IT WILL BE A WONDERFUL OPPORTUNITY TO TRY TO LEARN MORE ABOUT THE CROSS SECTIONAL INTERSECTION OF NEW DIAGNOSIS OF DIABETES AND THE DEVELOPMENT OF PANCREATIC CANCER WITH MONIES THAT ARE JOINTLY SUPPORTED BY NIDDK AND THE NCI. AGAIN THE DIVISION OF CANCER PREVENTION IS ALSO WORKING IN A PROGRAM ANNOUNCEMENT OF EARLY DIAGNOSE AND I GUESS HIGH RISK POPULATIONS AND BOTH POPULATIONS THAT ARE AT HIGH RISK FOREVER GENETIC REASONS AND ALSO THOSE INDIVIDUAL WHO IS HAVE CYSTIC DISEASES OF THE PANCREAS THAT PUT THEM AT ENHANCED RISK FOR DEVELOPING THIS DISEASE. AND WE'RE ALL INTERESTED IN THE APPROACHES OF NEW ORLEANS THERAPY WILL BE USEFUL AND OUR COLLEAGUES IN FREDERICK WHO HAVE SUPERVISED OUR PLANT FOR DEVELOPED BIOLOGICALS IF INSTANCES ARRIVE AND RECOMMENDATIONS FOR PRODUCING PANCREATIC CANCER EMUNE O THERAPY CLINICAL TRIALS AND THE CIT IS INTERESTED IN THIS DISEASE. AND FINALLY I GIVE YOU A SHORT UP DATE ON THE FAIRLY REMARKABLE PROGRESS THAT'S GONE ON IN JUST OVER A YEAR IN THE PROJECT AT FED RICK. THIS LIST GIVES YOU SOME OF THE ACTIVITIES BUT TO ME THE MOST RECENT, I HEARD THAT FRANK MCCORMICK UPDATE THE NCI IN THIS AREA AND AMONG THE THINGS THAT REALLY MOST INTERESTING ARE THE RAPID ABILITY TO PRODUCE A WHOLE RAFT OF DIFFERENT PROTEINS THAT WILL BE USEFUL AND COMPLETELY CHARACTERIZED AND USEFUL FOR THE STUDY FROM INTERACTIONS THAT VARIOUS PROTEINS ARE INVOLVED, AND SIGNIFICANT PROGRESS IN THAT AREA HAS BEEN MADE, AS HAS PROGRESS AND THE ATTEMPT TO MAP THE SURFACE OF THE KRASE MODEL EXPRESSING TUMOR CELLS WITH THE POTENTIAL OF IMMUNO THERAPEUTIC APPROACHES MIGHT BE USEFUL SO I THINK PROBABLY, THIS WILL BE A USEFUL THING TO DO MAYBE NOT AT OUR NEXT MEETING OR SUBSEQUENT MEETING TO GET AN UPDATE ON THE RAS PROJECT BECAUSE A LOT OF PROGRESS HAS BEEN MADE TODAY. I'M GOING TO INTRODUCE NOW BRIEFLY OUR HEAD OF COMMUNICATIONS. PETER GARRETT WILL UPDATE YOU ON THE REDESIGN OF THE NCI CANCER.GOV WEB SITE BECAUSE OF THE--THIS IS NOT ONLY A BIG EFFORT BUT EFFORT THAT REQUIRES A SUBSTANTIAL AMOUNT OF INPUT FROM OUR STAKEHOLDER COMMUNITY. >> THANK YOU JIM AND GOOD MORNING, EVERYONE, IT'S A PLEASURE TO BE HERE. JUST TO LET YOU KNOW, I TOOK OVER THE OFFICE OF COMMUNICATION THIS IS SUMMER, SO I'M NEW TO THE POST BUT I'M EXCITED ABOUT HAVING AN OPPORTUNITY TO TALK TO YOU TODAY AND GIVE YOU A QUICK AND HOPEFULLY USEFUL UPDATE ON WHAT WE CONSIDER TO BE A VERY IMPORTANT WAY TO COMMUNICATE OUR WEB SITE AND ALSO TO--I LOOK FORWARD TO INTERACTING WITH YOU IN THE FUTURE MEETINGS AS WELL. WE WILL KEEP PACE WITH THE WEB, WE KNOW THERE ARE CHANGES ALL THE TIME AND CHANGING OUR LIVES IN VERY DRAMATIC WAYS AND SOMETIMES SUBTLE BUT WE REALIZE HW DIFFERENT THEY THINKS ARE, IN ORDER TO KEEP PACE WITH THESE CHANGES AND ALSO WITH PUBLIC EXPECTATION, WE REDESIGN WANT THE CANCER.GOV WEB SITE CHRKS IS A BIG THING, HASN'T BEEN REDESIGNED IN OVER 10 YEARS. WE REALLY WANT THIS TO BE THE PLACE WHERE MOST CONFINED INFORMATION ABOUT NOT ONLY CANCER SO ONE OF THE THINGS IS A REALITY NOWADAYS AND I THINK IS THAT PEOPLE USE THE SITE, AND WHICH ENABLES THE CONTECT YOU SEE ON A WEB SITE TO BASICALLY ACCOMMODATE WHATEVER YOU'RE USING TO LOOK AT IT. MANY COME TO CANCER.GOV WITH A STRONG INTEREST IN CLINICAL RESEARCH AND TRIALS IN PARTICULAR. SO ONE OF THE THINGS WE WILL DO WITH THE NEW WEB SITE IS FEATURE CLINICAL TRIALS AND RESEARCH PROMINENTLY, AS WELL AS RESEARCH SECTION AND THROUGHOUT, AND PATIENTS ARE ACTUALLY SPEAKING ON INFORMATION ABOUT CANCER, THEY WILL BE ABLE TOACILY FIND INFORMATION ON CLINICAL TRIALS. AND LASTLY I WANT TO SAY THAT WE'RE DOING THIS VERY DELIBERATELY WITH VERY KEY AUDIENCES AND HERE ARE THE CATEGORIES THAT WE TEND TO GENERALLY THINK ABOUT WHEN WE'RE CONSIDERING THE--ABOUT FOUR MILLION VISITORS WE GET RIGHT NOW AT CANCER.GOV EVERY MONTH. WE BE THAT A MODEL CITIZEN JORRITY OF THOSE OF THE PUBLIC, FOLKS NEWLY DIAGNOSED, FAMILY MEMBERS OR FRIENDS, HEALTH PROFESSIONAL WHO IS COME TO OUR SITE FOR INFORMATION ABOUT CERTAIN DIAGNOSIS AND OBVIOUSLY NEW RESEARCH. THE RESEARCH COMMUNITY, VERY, VERY, IMPORTANT TO US AND IN THE NEW SITE WE'RE REALLY GOING TO MAKE RESEARCH A MORE EVIDENT THING AND MAKE IT CLEAR WHAT'S GOING ON SO RESEARCHERS WILL COME BACK OVER AND OVER AGAIN AND WE'RE NOT JUST THINKING THE EXTRAMURAL COMMUNITY BUT WE'RE ALSO THINKING ABOUT OUR OWN INTRANSLATIONAL RESEARCH MURAL COMMUNITY AND ADVOCATES KNOW WHAT'S GOING ON AND FINALLY INDUSTRY. SO TO MAKE SURE THAT WE'RE MEETING THE NEEDS OF ALL THESE FOLKS, WE'RE ACTUALLY GOING OUT AND DOING WHAT WE CALL USABILITY TESTING. AND THAT'S ESSENTIALLY GETTING PEOPLE IN A CONTROLLED SETTING AND WE HAVE A LAB WHERE YOU CAN WATCH BEHAVIOR BUT CAN YOU DO IT REMOTELY AND WE CAN HAVE SOMEBODY BASICALLY WORK WITH US AND WE CAN SEE WHAT KINDS OF THINGS THEY'RE LOOKING FOR, GIVES THEM TASKS AND MAKE SURE THEY'RE ABLE TO FIND THINGS ON THE SITE. SO I'M HAPPY TO ENTERTAIN ANY QUESTION FIST NOW'S THE TIME? >> WHAT'S THE TIME FRAME THAT YOU ENVISION IN TERMS OF WHEN THE NEW WEB SITE WILL BE UP AND RUNNING AND WHETHER IT'S ALL OF SORT OF AT ONCE OR ROLLED OUT SEQUENTIALLY? >> THE MAYBE DATE WILL BE MAY 15th, THANK YOU FOR ASKING THAT. I DID MEAN TO MENTION NA. >> JUST ANY ACISIONAL QUESTIONS? --ADDITIONAL QUESTIONS? >> I WOULD LIKE TO CLOSE BY INVITING YOU TO GIVE ME ANY SUGGESTIONS IF YOU HAVE THEM ABOUT THE WEB SITE, I WANT TO MAKE SURE THAT YOU HAVE MY E-MAIL ADDRESS AND KNOW YOU ALL ARE IMPORTANT USERS OF THIS INFORMATION AS WELL AND SO, WE WOULD WELCOME YOUR INPUT. YES? >> MY QUESTION IS WHETHER THERE WILL BE RESTRICTED ACCESS SITES OR ACCESS THAT IS LIMITED TO ANY GROUP FOR EXAMPLE RESEARCHERS IF THERE WILL BE A SITE WHERE WE WILL BE ABLE TO ACCESS INFORMATION THAT MIGHT NOT BE AVAILABLE TO THE ENTIRE PUBLIC. >> THE PLANS THAT WE HAVE RIGHT NOW, WITHIN THE OFFICE OF COMMUNICATIONS AND SUPPORING NCI BROADLY DO NOT INCLUDE THOSE KINDS OF SORT OF WORKPLACE SITES OR WHAT WE CAN ACTUALLY INTERACT BUT WE DO SEE THAT IN SOME OF THE OFFICES AND CENTERS WANT TO DO AND WE WANT TO SUPPORT THEM IN THAT WAY. >> WELL, THANK YOU FOR YOUR TIME. >> THANK YOU VERY MUCH. >> SO THIS WAS ONE OF MY FAVORITE PARTS OF THIS MEETING ON A YEARLYY BASIS WHERE I GET TO INTRODUCE TO YOU SOME OF THE OUTSTANDING INDIVIDUAL WHO IS COMPLETED SUCCESSFULLY FOR THE LEADERSHIP AWARD THIS IS PAST YEAR. AND JUST TO REMIND YOU THIS IS ONE OF THE RECOMMENDATIONS OF THE CLINICAL WORKING BOARD TAKEN--THEY WE TRY TO DO WHATEVER WE COULD TO RECOGNIZE AND SUPPORT THOSE INDIVIDUALS AT YOUR CANCER CENTERS WHO PARTICIPATE EXTENSIVELY IN NCI FUNDED COLLABORATIVE RESEARCH ACTIVITIES, BUT WHO SELDOM ARE RECIPIENTS OF INDIVIDUAL PEER REVIEW AWARDS. THEY ARE THE GLUE THAT KEEPS THE CLINICAL AND TRANSLATIONAL RESEARCH ACTIVITIES TOGETHER AND OFTEN THEY SIMPLY DON'T GET THE KIND OF RECOGNITION THAT THEY SHOULD. WE HAVE SO FAR RECOGNIZED ALMOST 70 INDIVIDUALS, TWO YEAR-OLD AWARDS, BASICALLY $50,000 A YEAR THE IDEA WAS TO BUY A DAY AWAY SO THEY WOULDN'T HAVE TO GO TO CLINIC AND THEY HAVE DESIGNATED TIME SO THEY CAN FOCUS ON THE CLINICAL AND TRANSLATIONAL RESEARCH ACTIVITIES THAT THE CANCER CENTERS THAT RECEIVE SO THIS MONEY AND THEIR NAMES. THIS GIVES YOU A LIST, I WON'T GO THROUGH THE BULLETS BUT IT'S A COMPREHENSIVE LIST OF ALL THE THINGSES THAT GO ON AT YOUR CENTERS THAT ARE ESSENTIAL: WHETHER IT'S TRAINING, MANNING THE IRB, PARTICIPATING ON IN GROUPS THAT ARE CRITICAL FOR A PROJECT GRANT OR ANY KIND OF MULTIINVESTIGATOR GRANT WHERE SAMPLES NEED TO COME FROM A PARTICULAR GROUP OF PATIENTS AND YET THERE'S NEVER ENOUGH MONEY TO PAY FOR THE ACQUISITION OF THOSE SAMPLES AND THERE'S SELDOM IF EVER ANY MONEY TO RECOGNIZE THE CLINICIANS WITHOUT WHOM THE SAMPLES WILL NOT GET TO THE APPROPRIATE LABORATORY. WE ALSO HAVE INDIVIDUAL WHO IS SPEND A GREAT DEAL OF TIME CHAIRING OR PARTICIPATING VERY ACTIVELY BEFORE THE SCIENTIFIC REVIEW COMMITTEES BY CTSG GUIDELINES BEFORE THE STUDY GUESS FORWARD SO THERE ARE NUMEROUS ACTIVITIES I WISH--IT WASN'T POSSIBLE, BUT I WISH IT WAS POSSIBLE TO SHARE THE DOES HE SCRIPGZ OF THESE INDIVIDUAL'S ACTIVITIES AT YOUR CENTERS. BECAUSE NUMBER ONE YOU WOULD ALL BE PROUD YOU HAVE SUCH INDIVIDUALS AND IT WOULD BE ABUNDANTLY CLEAR HOW IMPORTANT THEY ARE TO THE ACTIVITIES AT YOUR SITES. THESE ARE HOUR AWARDS THAT ARE--THEY COME FROM THE NOMINATION OF THE CANCER CENTER DIRECTOR, WE CAN REALLY FUBBED ONE INDIVIDUAL EVERY TWO YEARS AT AN NCI SUPPORTING CENTER, THEY HAVE TO BE A PRACTICING CLINICAL ONCOLOGIST IN WHATEVER DISCIPLINE. IT DOESN'T MATTER WHETHER THEY'RE A PHYSICIAN, NURSE, PSYCHOLOGIST, ET CETERA BUT THEY HAVE TO PLAY A CRITICAL ROLE IN YOUR CRITICAL TRIALS OPERATIONS. A GROUP OF SENIOR STAFF THAT THE NCI APPLICATIONS AND AS I SAY, THE BIGGEST PROBLEM YEAR TO YEAR IN AN ONGOING BASIS THAT WE HAVE IS THAT IT'S VERY RARE THAT THERE ARE EVEN A FEW OF THE FOLKS WHO ARE SUBMITTED AND SENDING OUT, FOR THE APPLICATIONS WE RECEIVE, WOULDN'T BE APPROPRIATE TO BE FUNDED SO WE COULD FUND 20 OR 25 INDIVIDUALS A YEAR IF WE HAD THE MONEY BECAUSE THERE ARE OUTSTANDING FOLKS THAT YOU WORK WITH THAT YOU WANT TO RECOGNIZE. SO LET ME RUN THROUGH THE INDIVIDUALS. SO FROM THE HUNTS MAN CANCER CENTER, WE HAVE: ROBBER ... >> THEY'RE NOT HERE BUT IF I COULD ASK YOU FOR A ROUND OF APPLAUSE FOR THESE INDIVIDUALS. [ APPLAUSE ] THEY REALLY ARE OUTSTANDING AND WE DID THIS A COUPLE YEARS AGO, AND WE SHOULD DO IT IN ANOTHER YEAR OR TWO, WE BROUGHT IN PREVIOUS AWARDEES AND YOU HEARD FROM THEM AND IT'S REALLY QUITE WONDERFUL, TO HEAR, WE WON'T USE NAMES BUT THERE WAS AN INDIVIDUAL WITH BREAST CANCER AT A LOCAL INSTITUTION, NOT TOO FAR FROM HERE WHO WAS INTERMEDIATE, JUNIOR TO INTERMEDIATE WHEN HE GOT THIS AWARD AND NOW IS ON A MAJOR NATIONAL COMMITTEE AND THAT--THAT STORY RINGS TRUE FOR A VARIETY OF THESE INDIVIDUALS. AND HE SPECIFICALLY TOLD US, HE WASN'T GOING TO GET ANYMORE MONEY FOR US AND HE WASN'T TRYING TO MAKE HIM FEEL GOOD BUT THE FACT THAT HE HAD A PICTURE WITH THAT AWARD, IT GOT INTO THE NEWS LETTER FOR THE CANCER CENTER, THE DEAN SAW IT AND THESE THINGS--THEY WEREN'T BIG DEALS IN THE BIG PICTURE, THEY'RE NOT MULTIMILLION DOLLAR GRANTS BUT THEY ARE FOR THESE INDIVIDUALS THEY MEAN A LOT. SO I APPRECIATE ALL OF THE EFFORT THAT GOES INTO TRYING TO DO THIS. BOTH IN YOUR END AND WITH INDIVIDUALS TO HAVE THE ABILITY OF THE FUNDS TO DO IT. SO LAST BUT NOT LEAST IN MY SECTION IS TO RECOGNIZE THE RETIRING CTAC MEMBERS, OUR RETIREES, LISA I DON'T THINK IS HERE YET. SHE WILL GET HER PLAQUE, HE ISN'T COMING TO THE MEETING BUT THE PLAQUE IS BETTER THAN HAVING HER PICTURE TAKEN WITH ME, I CAN'T IMAGINE THAT WOULD BE SOMETHING THAT WOULD BE FOR HER WALL, IT'S A PLAQUE, TELL BE A NICE ONE SO TELL BE ON THE WALL BUT MOSTLY I JUST WANT TO--IN THANKING THEM, CONTINUE TO THANK YOU FOR COMING TO THESE MEETINGS, YOU KNOW IT SEEMS LIKE EVERY TIME WE HAVE ONE, THERE'S ANOTHER SET OF WORKING GROUPS AND SUBCOMMITTEES THAT WE ASK YOU TO CHARGE AND THAT INVOLVES MORE WORK AND I WON'T TELL YOU THAT ISN'T GOING TO CONTINUE IN FACT IT WILL CONTINUE VERY SOON WHEN WE ASK THR THESE THINGS IN THE NEAR FUTURE. SO I DON'T KNOW, SHOULD WE ADDRESS THIS AT THIS TIME? >> WELL, FIRST OFF LET ME--COUPLE HOUSEKEEPING THINGS. FIRST I WOULD LIKE TO WELCOME DAVID BANKROFD TO THE COMMITTEE. WE'RE BELIGHTED TO HAVE YOU HERE. AND PHIL KEEBLER, CAME IN, ANY QUESTIONS FOR JIM? >> NANCY? >> IT'S EXCITING TO SEE THESE FOR THE CLICAL TRIALS GROUP. WHO DOES THOSE? >> WE INVOLVE INDIVIDUALS--WELL, I COULD NAME NAMES BUT I DON'T THINK IT MAKES A HUGE DIFFERENCE SO WHEN THE WIFE IS INVOLVED, THERE ARE APPLICATION TO SUPPLEMENTS AND CANCER CENTERS AND INDIVIDUALS IN HER GROUP AND WE HAVE INDIVIDUALS AND INDIVIDUALS IN CTEP, IN THE DIAGNOSIS PROGRAM, IN DCP SO IT'S REALLY AN INSTITUTE WIDE SENIOR LEADERSHIP GROUP. >> WE DO HAVE EXTERNAL REVIEWERS THAT LOOK AT THEM AS WELL AND CORRELATE THE SCORES AND THERE'S SENIOR LEADERSHIP GROUP THAT ARE REVIEWING AND MAKE THE FINAL RECOMMENDATIONS. >> ANY OTHER QUESTIONS. >> CMS IS EVALUATING NOW, A SCREEN INITIATIVE AND IT BECAUSE SMALL CELL LUNG CANCER IT'S SO FAR ADVANCED AT THE TIME OF DIAGNOSIS HAS THERE BEEN ANY DISCUSSION WITH CMS IN TERMS EVER THIS SCREENING INTERNAL AUDITTISHIAATIVE IF THEY'RE CONSIDERING IF THERE'S CONNECTIONS BETWEEN THE TWO PROGRAMS AND WHETHER OR NOT THE SCREENING MIGHT ALLOW SOME BENEFIT OR SOME INFORMATION GAINING IN TERMS OF OUR INITIATIVE. >> SO BEAR KRAMER FROM DCP AND PAULA JACOBS FROM THE IMAGING PROGRAM HAVE BEEN ACTIVELY INVOLVED AND WERE ACTIVELY INVOLVED IN DISCUSSIONS DUE TO CMS'S WORDS OF WISDOM ABOUT HOW THEY'LL GO FORWARD WITH THE LOCAL CTSCREENING SO WE'VE HAD AN ACTIVE ROLE AND HOW THEY PUT TOGETHER THEIR DATABASE IS REALLY NOT--WE OFFER OUR OPINION ABOUT HOW THAT SHOULD BE DONE BUT THAT SHOULD BE UP TO CMS AND ONE THING THAT WAS DISCUSSED I THINK AT LENGTH AT THESE SMALL CELL LUNG CANCER, THEY PUT TOGETHER THE REPORT FOR THE CANCER'S ACT THE DATA FROM MLST, WITH RESPECT TO SMALL CELL IS ACTUALLY VERY DISAPPOINTING. THERE'S NO QUESTION THAT A COUPLE HUNDRED PATIENTS EARLY LESIONS WERE DETECT BUD THERE'S NO EVIDENCE THAT THE DETECTION HAD ANY IMPACT ON SURVIVAL. THE PROGRAM ANNOUNCEMENT FOR DIVISION ANNOUNCEMENT PREVENTION IS CONSIDERING IS NOT ONE THAT WILL BE LOOKING MORE I BELIEVE--CAN'T SWEAR TO THIS, IS FINDING MOLECULAR MARKERS IN BLOOD RATHER THAN IMAGING CORRELATE OF EARLY DETECTION FOR SMALL CELL. >> ANY ADDITIONAL QUESTIONS? OKAY, IF NOT ON THE SLIDE YOU SEE AS MENTIONED EARLIER WE WANT TO EXPLAIN A MOTION FOR TWO WORKING GROUPS TO OVERSEE THE PROGRESS FOR THE RECALCITRANT ACT AS IT RELATES TO SMALL LUNG CELL CANCER AND PANCREATIC CANCER. I WOULD LIKE TO ENTERTAIN A MOTION IF POSSIBLE. >> SECOND. >> AND SECONDED. >> ALL IN FAVOR? AND ANY OPPOSED? AND ANY ABSTENTIONS? >> WE WILL PROCEED, THANK YOU VERY MUCH. JUST ONE OTHER QUICK HOUSEKEEPING NOTE, I FAILED TO MENTION THAT IN THE BOOK ARE THE FUTURE MEETING DATES FOR THE COMMITTEE. THEY'RE ENUMERATED THROUGH 2016. SO THIS GIVES YOU AN OPPORTUNITY TO GET THESE ON TO YOUR SCHEDULE, WELL IN ADVANCE OF THE MEETING. SO PLEASE JUST REFER TO THAT WHEN YOU CAN. AT THIS POINT I THINK WE'RE GOING TO MOVE TO THE LEGISLATIVE UPDATE. THERE'S BEEN A LOT OF INTERESTING ACTIVITY OVER THE LAST FEW WEEKS AND IT'LL BE TO SEE HOW THOSE CHANGES MIGHT EFFECT OUR WORK. SO SUSAN WILL GIVE US OUR LEGISLATIVE UPDATE. >> OKAY, THANK YOU. >> THANK YOU AND GOOD MORNING, VERY PLEASED TO BE HERE TO REPORT ON THE LEGISLATIVE ACTIVITIES. I THINK THE SORT OF THE TWO MAJOR TOPICS I THINK WILL BE OF INTEREST TO YOU IS WHAT WILL HAPPEN IN THE LAME DUCK SESSION IS WHATEE CAN EXPECT TO SEE IN THE NEW CONGRESS WHICH WILL START IN JANUARY. WE WILL START IN THE LAME DUCK SESSION AND TALK A LITTLE BIT ABOUT APPROPRIATIONS AND THE KEY ISSUES OF THE LAME DUCK SESSION THAT WILL WE NEED TO BE CONSIDERING. SO THE STATUS OF APPROPRIATION, THE MOST IMPORTANT THING TO KEEP IN MIND IS RIGHT NOW WE'RE ON A CR THAT'S IN EFFECT UNTIL DECEMBER 11th, BUT I WANT TO SORT OF REVIEW HOW WE GOT HERE. WHY WE HAVE A CR. INSTEAD OF A BILL. IN THE HOUSE THE LABOR HHS SUBCOMMITTEE DID NOT RELEASE EITHER A BILL OR A REPORT THIS YEAR. SO WE DON'T KNOW WHAT THE MAJORITY FEELS IN TERMS OF THOSE INDIVIDUAL FUNDING LEVELS FOR PROGRAMS WITHIN THE LABOR HHS BILL. THE MINORITY MEMBERS OF THE COMMITTEE DID RELEASE THEIR OWN PROPOSAL ON SEPTEMBER 15th THIS WAS SORT OF A FORMALITY. NOT EXPECTED TO HAVE MUCH OF A IMPACT ON HOW THE SUBCOMMITTEE MOVES THERE ARE 12 APPROPRIATIONS BILLS. THE OTHER 11 WERE PASSED BY THE SUBCOMMITTEE AND THE FULL COMMITTEE. AND SEVEN OF THOSE BILLS WERE PASSED BY THE FULL HOUSE. SO THE HOUSE WAS ABLE TO ACCOMPLISH A LOT, BUT NOT WITH THE LABOR HHS BILL, IN THE SENATE OUR SUBCOMMITTEE DID VOTE ON A BILL AND DID REPORT ON JUNE 10th. THIS WAS ONE OF THE BILLS PASSED BY THE SUBCOMMITTEE AND EIGHT BILLS WERE PASSED BY THE FULL COMMITTEE BUT LABOR H WAS NOT ONE OF THOSE. SO WHAT CONCLUSION, I THINK WE CAN REACH FROM THIS IS THAT THERE WAS SOME AGREEMENT AMONG THE APPROPRIATORS ON HOW TO PROCEED IN MANY OF THE AREAS BUT LABOR HHS WAS NOT ONE OF THEM. THERE IS A 1.1 BILLION DOLLAR DIFFERENCE IN THE ALLOCATION TO THE LABOR HHS SUBCOMMITTEE BETWEEN THE HOUSE AND THE SENATE. SO THAT'S NOT TERRIBLY FAR APART. MANY, MANY BILLIONS A PART LAST YEAR--OR LAST YEAR, SO IT SEEMS LIKE WHEN THEY DO START TO SIT DOWN AND WORK ON IT WON'T BE INSURMOUNTABLE. SO LEADING UP TO THE CR, THERE ARE LOTS OF GOOD INTENTIONS ON EVERYONE'S PART, THIS IS WHAT THE CHAIRMAN OF THE HOUSE APPROPRIATIONS COMMITTEE SAID HE WANTED TO MOVE FORWARD WITH A CR SO THAT WOULD ALLOW TIME TO DRAFT THESE BI-CAMMURAL PIECES OF LEGISLATION THAT AFFECT THE REQUIREMENTS AND THEN THE FOLLOWING DAY WE HEARD FROM SENATOR Mc CLUSKY AS CHAIR OF THE APPROPRIATIONS COMMITTEE. SHE SEES THE BRIDGE AS THE OMNIBUS, SETS THE STAGE FOR CONGRESS TO COME TOGETHER. SO I THINK AT THAT POINT IN MIDSEPTEMBER, EVERYONE HAD WONDERFUL INTENTIONS ABOUT GETTING THIS OFF OF THE--OFF OF THEIR LIST IN SEPTEMBER PUTTING IT FORWARD INTO THE LAME DUCK SESSION BUT THEIR INTENTION WAS CLEARLY TO DO AN OMNIBUS BILL THAT WOULD INCLUDE THE INDIVIDUAL BILLS. THE REALITY TODAY, NOVEMBER 12th, WE ARE OPERATING THURPD CONTINUING RESOLUTION AND TODAY IS THE DAY THAT CONGRESS RETURNS TO BEGIN THE LAME DUCK SESSION, SO THEY ARE GOING TO NEED TO ACTOT FY15 FUNDING PRIOR TO DECEMBER 11th AND SO WHAT ARE THERE OPTIONS HERE? WELL, AS EVERYONE WAS SAYING THEY DIDN'T INTEND TO DO AN OMNIBUS BILL AND THAT IS CERTAINLY A POSSIBILITY. ANOTHER OPTION IS TO JUST TAKE THAT CR AND EXTEND IT FOR THE FULL YEAR FOR ALL OF THE BILLS THAT IS PRETTY PROBLEMATIC. IN TERMS OF NOT BEING ABLE TO INFLUENCE ANY OF THE INDIVIL BILLS, NOT BEING ABLE TO MAKE ANY CHANGES. THERE'S A COMBINATIONS, WE THE OMNIBUS, MINIBUS AND NOW WE HAVE THE CROM-NIBUS. WHICH IS A COMBINATION OF THE CR AND AN AMNIBUS. THEY STARTED TALKING ABOUT THIS IN THE LAST WEEK OR TWO AND WHAT THIS WOULD BE IS SOME BILLS WOULD BE PUT INTO THE NATIONAL LIBRARY OF MEDICINE NIBUS, SOME OF THEM WHERE THERE IS QUITE A BIT OF AGREEMENT, IT WOULD GO INTO AN OMNIBUS BILL AND THEN THE CR FOR THE PROBLEMATIC BILLS. SO AS I MENTIONED, LABOR H IS ONE OF THOSE PROBLEMATIC BILLS. SO, YOU KNOW THAT'S JUST ONE OF THE OPTIONS IS TODAY'S THE FIRST DAY SO WE'LL WAIT AND SEE HOW THAT PROCEED, WE DO KNOW THAT THE STAFF APPROPRIATIONS STAFF AND BOTH THE HEALTH AND THE SENATE HAVE BEEN WORKING VERY DILIGENTLY TO GET THEIR BILLS IN ORDER TO MAKE AN EFFORT TO MOVE THEM FORWARD IN AN OMNIBUS. SO AS I SAID THERE FIRST PRIORITY IS TO DO SOMETHING ABOUT PASSING APPROPRIATIONS BILLS. THEY NEED TO CONSIDER EMERGENCY APPROPRIATIONS PRIMARILY FUNDING FOR EBOLA OUTBREAK AS WELL AS NEW MILITARY OPERATIONS AND ANOTHER VERY IMPORTANT THING THAT WILL BE ADDRESSED IN THE LAME DUCK SESSION IS NONAPOPTOTIC SETTLE THE DIFFERENCES IN THE DEFENSE AUTHORIZATION BILL. THIS IS A BILL THAT IS AUTHORIZED EVERY YEAR, HAS BEEN AUTHORIZED EVERY YEAR AND THEY DON'T WANT TO SORT OF BREAK THAT RECORD. SO THE HOUSE AND THE SENATE DEFENSE, THE ARMED SERVICES COMMITTEES WILL BE WORKING TO SEND--MOVE FORWARD A DEFENSE AUTHORIZATION BILL. SO THOSE ARE PRETTY BIG THINGS THAT WILL KEEP THEM OCCUPIED FROM TODAY UNTIL HOWEVER ALONG THEY CHOOSE TO WORK AND I THINK ONCE THEY--ONCE THEY GET THESE THREE THINGS OUTS OF THE WAY, THEY'LL BE PROBABLY HEADING OUT OF TOWN. ANOTHER THING THAT'S HAPPENING IN THIS TIME FRAME IS THE NEW MEMBERS OF CONGRESS ARE BEGINNING THEIR ORIENTATION SESSIONS. SO THOSE ARE BEGINNING THIS WEEK FOR BOTH NEW MEMBERS OF THE HOUSE AND NEW MEMBERS OF THE SENATE. SO ONCE THE LAME DUCK SESSION WRAPS UP, JANUARY WILL COME AND THE NEW MEMBERS WILL BE SWORN IN SO I WOULD LIKE TO TELL YOU ABOUT THE NEW MEMBERSHIP OF THE--WHAT WILL BE THE 114th CONGRESS, SOME OF THE MAJOR DIFFERENCES WE EXPECT TO SEE AND THE COMMITTEES AND SOMETHING ABOUT THEIR PRIORITIES MOVING FORWARD. SO AS OF MONDAY THERE WERE SIX RACES STILL UNDECIDED AND IN ADDITION TO THAT, THE LOUISIANA SENATE RACE WHERE MARY LANDRIEU WILL BE COMPETE NOTHING A RUN-OFF ELECTION ON DECEMBER 6. THAT WILL BE SETTLE OFFICE OF DIVERSITY DECEMBER 6th. IF THE PROJECTIONS OF THESE UNDECIDED RACES HOLD THE SENATE WOULD LIKE LOOK LIKE THIS WITH 56 REPUBLICANS 42 DEMOCR TWO OF THOSE ARE INDEPENDENTS HOWEVER BOTH INDEPENDENTS CONFIRM THAT THEY PLAN TO CAUCUS WITH THE DEMOCRATS AGAIN IN THIS CONGRESS. AND THERE WAS SOME DOUBT ABOUT THAT AT VARIOUS POINTS. 21 MEMBERS OF THE SENATE WILL BE WOMEN AND SIX MINORITY MEMBERS. THE 21 WOMEN IS ASSUMING ACTUALLY MA MARY LANDRIEU WILL NOT WIN HER PRIMARY SO THAT COULD GO UP TO 22. IN THE HOUSE WE'RE LOOKING AT 247 REPUBLICANS AND AND 188 DEMOCRATS. THERE ARE NO CHANGES EXPECTED IN THE OVERALL PARTY LEADERSHIP. THE SPEAKER THE MAJORITY MINORITY LEADERS HAVE INDICATED THEY WILL BE RUNNING AGAIN. THEY WILL HAVE TO BE ELECTED BY THE CAUCUSES. BUT THERE ISN'T ANY EXPECTATION THAT THE LEADERS FROM THE LAST CONGRESS WILL ALSO NOT BE THE LEADERS IN THE COMING CONGRESS. SO IN TERMS OF THE COMMITTEES, WE WILL HAVE ALL NEW CHAIRS BECAUSE THE MAJORITY IS HELD BY THE REPUBLICANS. THE RATIOS OF THE NUMBER OF ONE PARTY ON EACH COMMITTEE AND THE NUMBER OF THE OTHER PARTY, THE ACTUAL RATIO WILL NOT CHANGE BUT THEY WILL FLIP. THERE WILL BE ADDITIONAL SO THERE WILL BE A LOT OF REPUBLICAN MEMBERS ADDED TO THE COMMITTEES. AND IN SOME COMMITTEES THEY WILL HAVE NEW CHAIRS OR MEMBERS DUE TO RESIGNATIONS OR DEFEATS IN THE ELECTION AND ALSO TERM LIMITS. SO SOME OF THE PEOPLE THAT HAVE LEFT THAT ARE OF PARTICULAR NOTE, HENRY WAX MAN HAS RETIRED, HE HAS BEEN THE RANKING MEMBER OF THE ENERGY AND COMMERCE COMMITTEE AND WE WILL HAVE A NEW RANKING MEMBER THERE. THAT'S PROBABLY THE--WELL, YEAH, THAT'S PROBABLY THE BIGGEST ONE. THE RATIOS WILL DEFINITELY CNGE SINCE THE REPUBLICANS GAIN SO MANY SEATS IN THE HOUSE. SO IN THIS POINT IN THE 113th CONGRESS THERE WILL WERE ABOUT FIVE OR SIX MORE REPUBLICAN MEMBERS ON EACH COMMITTEE THAN THERE WERE DEMOCRS SO THERE WILL PROBABLY BE SOME NUMBER HIGHER THAN THAT IN THE NEXT CONGRESS. SO TALKING ABOUT THE COMMITTEE, SENATOR Mc CULLS SKI WILL NOW BE THE RANKING MEMBER BUT IN TERMS OF WHOLE BE THE CHAIR, THERE'S NOT REAL CERTAINTY WHETHER IT WOULD BE SENATOR COCHRAN OR SENATOR SHELBY, MOST OF THE THINKING RIGHT NOW IS THAT IT WILL BE SENATOR COCHRAN, BUT THAT'S A DECISION THAT THE EACH CAUCUS WILL MAKE AND OUR SUBCOMMITTEE, SENATOR MORAN IS EXPECTED TO BE THE CHAIR OF LABOR H AND THERE WILL NEED TO BE A REPLACEMENT FOR SENATOR HARKIN WILL NOT BE THERE TO BE THE RANKING MEMBER. SO THERE'S NOT REAL DEFINITE WORD ON WHO THAT MIGHT BE. COULD BE PATTY MURRAY. WE JUST--DON'T KNOW THAT YET. ON THE SUBCOMMITTEE, SENATOR ALEXANDER IS EXPECT TUBED THE CHAIR HOWEVER SENATOR ENZI WHO HAD BEEN TERM LIMITED AS A CHAIR DOES NOT HAVE ENOUGH TERMS AS THE RANKING MEMBER TO LIMIT HIM. SO HE COULD THROW HIS HAT IN THE RING TO BE THE CHAIRMAN OF THE SENATE HEALTH COMMITTEE. SENATOR MURRAY IS EXPECTED TO BE THE RANKING MEMBER ON THE SENATE HEALTH COMMITTEE AND IF SHE ALSO STAYS ON THE BUDGET COMMITTEE SHE MAY NOT WANT TO BE THE RANKING COMMITTEEOT HEALTH COMMITTEE THAT'S WHY THERE'S UNCERTAINTY THERE, HOUSE PROARPTIONS, THE BIG QUESTION MARK IS WHO WILL CHAIR THE LABOR HHS SUBCOMMITTEE AND CONGRESSMAN KING STONE LOST IN HIS BID FOR THE SENATE ELECTION SO HE WILL NOT BE RETURNING. THERE ARE MEMBERS THAT HAVE BEEN THERE IN THE 113th CONGRESS WHO EXPRESSED INTEREST, PRIMARILY CONGRESSMAN ANDY HARRIS OF HAIR MARE. HOWEVER HE DOESN'T HAVE A LOT OF SENIORITY SO THAT'S DEFINITELY NOT A SURE THING AND THERE'S JUST A LOT OF SHUFFLING THAT WILL TAKE PLACE AND WE DON'T KNOW YET. BUT WE DO EXPECT THAT OUR RANKING MEMBER WILL STAY ON IN THAT ROLE THE HOUSE ENERGY AND COMMERCE COMMITTEE, CHAIRMAN UPTON WILL STAY ON IN TERMS OF WHO THE MEMBER WILL BE THIS IS WHERE HENRY WAX-MAN COMES INTO PLAY, THE CONGRESSMAN AND WOMAN FROM CALIFORNIA HAVE SHOWN INTEREST AND HAVE BEEN WORKING TO BECOME THE RANKING MEMBER ON THAT VERY LARGE AND VERY IMPORTANT COMMITTEE. NANCY PELOSI HAS ENDORSED CONGRESS WOMAN PISHU. CONGRESSMAN PITS IS CURRENTLY THE CHAIR OF THE HEALTH SUBCOMMITTEE. MY GUESS IS BOTH P A LONE AND ISHU, IS ON THE HEALTH SUBCOMMITTEE. MY GUESS IS WHOEVER DOESN'T GET THE RANKING OF THE FULL COMMITTEE MAY BECOME THE MEMBER OF THE HEALTH SUBCOMMITTEE. SO IN TERMS OF WHAT THE PRIORITIES OF THE NEW CONGRESS WILL BE TON OF LEADERSHIP FOR THE PRIORITIES AND WHAT THE PRIORITIES ARE, BUT I THINK THEY'RE STILL BEING SORTED OUT SO I WASN'T GOING TO MENTION ANY OF THOSE. I THOUGHT THE MOST RELEVANT NEW PRIORITY IS TALKED ABOUT IN THIS STATEMENT THAT CHAIRMAN UPTON PUT OUT ON THE DAY AFTER THE ELECTION RELATIVE TO THE 21st CENTURY CURES INITIATIVE AND I DON'T KNOW HOW MANY OF HAVE YOU BEEN FOLLOWING THIS BUT THIS IS SOMETHING THAT HE AND CONGRESS WANTED TO GET BEGAN IN THE LAST CONGRESS THEY'VE HELD NUMEROUS MEET NOTHING WASHINGTON HEARING FROM THEIR DISTRICTS AND HEARING FROM A LOT OF PEOPLE IN DIFFERENT AREAS AND WE TALK ABOUT THIS IN THE STATEMENT, WE TALK ABOUT PATIENTS, RESEARCHERS CAREGIVERS AND INNOVATORS. AND THEY ARE LOOKING, THEY WOULD LIKE TO BE ABLE TO MOVE FORWARD TO FIND TREATMENTS FOR THE THOUSANDS OF DISEASES WITHOUT TREATMENTS. AND SO, HE'S SAYING HIS PRIORITY NOW FOR THE COMING CONGRESS IS TO CONTINUE TO ADVANCE THIS INITIATIVE. AND WE ARE STARTING TO HEAR ABOUT SOME DRAFT LEGISLATION THAT THEY ARE WORKING ON THAT WILL FOLLOW THROUGH ON SOME OF THE THINGS THAT THEY HAVE LEARNED IN THOSE 21st CENTURY CURES HEARINGS. SO I'M GOING TO STOP THERE AND SEE IF THERE ARE ANY QUESTIONS I CAN ANSWER. >> THANK YOU, QUESTIONS? LEE? >> SO ONE QUESTION IS YOU SORT OF INTIMATED THAT ONE OPTION WOULD BE TO EXTEND THE CR FOR THE ENTIRE YEAR. BUT COULD BT THEY EXTEND IT TO THE NEXT CONGRESS, THAT WOULD BE THE MORE LIKELY GUESS, RIGHT? >> I FORGOT TO SAY THAT AND SO THANK YOU VERY MUCH. THEY COULD EXTEND IT FOR THE FULL YEAR, AND SOME PEOPLE TALKED ABOUT THAT WHEN THE NEW CONGRESS STARTS THEY CAN START UP ON THE NEXT YEAR FISCAL APPROPRIATIONS CLEAN AND SO, I THINK SOME PEOPLE WOULD PREFER THAT BUT DEFINITELY, IT IS AN OPTION TO PASS THEN ANOTHER SHORT-TERM CR WHICH WOULD TAKE US TO PERHAPS SOMETIME AT THE END OF JANUARY OR MIDFEBRUARY, SO DEFINITELY THAT'S ANOTHER OPTION. >> ANY ADDITIONAL QUESTIONS. OKAY, THANK YOU VERY MUCH. THAT WAS VERY COMPREHENSIVE. SO I THINK WE'RE A LITTLE BIT AHEAD OF TIME BUT I THINK WE WILL MOVE TO THE NEXT ITEM WHICH IS DR. LEE HELMAN WHO IS UPDATE THE COMMITTEE AND SEEKING INPUT FROM US ALL ABOUT FEEDBACKOT NIH AND NCI'S SORT OF--PLANS FOR THE INTRAMURAL RESEARCH AND THE INPUT THAT YOU KNOW REALLY SEEKING IS HOW THE COMMITTEE WOULD LIKE TO HAVE INPUT IN TERMS OF ENHANCING ESPECIALLY INTRAMURAL AND EXTRAMURAL COLLABORATIONS AND AS I THINK HE'LL SPEAK TO, AROUND SOME OF THE MORE UNUSUAL OR RARE CANCERS THAT WE ALL DEAL WITH. LEE? >> THANK YOU, JIM. SO SHEILA ASKED ME TO UPDATE THIS ONGOING PROCESS AND I HAVE TO APOLOGIZE TO LOU, BECAUSE HE'S BEEN ON THE COMMITTEE AND HEARD SOME OF THIS ALL RIGHT, AND THANK YOU FOR YOUR WORK ON THIS LOU, BUT JUST FOR THOSE WHO DON'T KNOW, EARLY THIS YEAR FRANCIS COLLINS CHARGED ALL THE EN--STRATEGIESITUTES WITH DEVELOPING A LONG-TERM PLAN WITH THE BROAD GOAL OF DEVELOPING A 10 YEAR VISION. AND WE QUICKLY FELT 10 YEARS WAS WAY TOO FAR AHEAD AND WE WERE SORT OF MORE FOCUSING ON ON A FIVE YEAR BUT HIS GOALS WERE TO DEVELOP LARGE SCALE INITIATIVE THAT CAPITALIZE ON DISTINCTIVE FEATURES OF THE GLOBAL NIH INTRAMURAL PROGRAM AND TO DEVELOP A BLUEPRINT FOR MAINTAINING SCIENTIFICALLY DISTIRVEGHTIVE AND OUTSTANDING SCIENCE SPECIFICALLY ALSO INCLUDING A SUSTAINABLE CLINICAL RESEARCH CENTER. SO OUR OWN NCI, IRP VISION, AS WE ENTER INTO THIS WAS TO SUPPORT THE MISSION BY IDENTIFYING PROJECTS FOR BROAD COLLABORATIONS, BOTH ACROSS THE NCI, INTRAMURAL RESEARCH PROGRAM AND ALSO TO STRENGTHEN NIH COLLABORATIONS AND COLLABORATIONS ACROSS NCI DIVISIONS AND ALSO EXPAND OPPORTUNITIES FOR COLLABORATION WITH EXTRAMURAL COMMUNITY AND/OR AND INDUSTRY. OBVIOUSLY WE WERE LOOKING AT IMPORTANT ISSUES TO IMPROVE THE USE AND FISCAL HEALTH OF THE CLINICAL CENTER TO TALK ABOUT ORGANIZATIONAL ELEMENTS THAT ENHANCE DISTINCTIVENESS AND THE SUCCESS OF THE IRP AND TO IDENTIFY BARRIERS AND I'M GOING TO NOT REALLY FOCUS TOO MUCH ON THE BARRIERS BUT MORE ON WHAT WE'RE TALKING ABOUT. SO THIS WAS THE TIMELINE. IT WAS REALLY PRETTY COMPRESSED. WE HAD TO HAVE A REPORT TO THE NIH IN OCTOBER--IN AUGUST 10th AND ALL THE REPORTS FROM ALL THE INSTITUTES WERE SORT OF PUT INTO ONE REPORT AND THAT GOES TO THE ADVISORY COMMITTEE TO THE NIH DIRECTOR AND THEIR DRAFT REPORT WAS DUE AT THE END OF OCTOBER AND THIS WILL BE PRESENTED IN A FEW WEEKS, DECEMBER 12, TO THE FULL REPORT, TO THE SUBCOMMITTEE AND THE SUBCOMMITTEE OF THE ACD WILL GIVE THE FULL REPORT AND I'M SURE THERE WILL BE LOTS OF DISCUSSION. SO THIS WAS OUR COMMITTEE AND YOU CAN SEE, ALL OF THE ICs FORM THE COMMITTEE THAT WAS 50% SENIOR STAFF FROM THE INSTITUTES OF 50% EXTRAMURAL MEMBERS AND SO, WE CHOSE OUR COACH CO--CHAIRS OF OUR BFC, OTHER MEMBERS LISTED HERE, YOU PROBABLY KNOW MOST OF THEM, MANY FROM OUR BSC THIS IS SCHEME AND MEMBERS ACROSS TED CCR. SO JUST TO TAKE STOCK IN IN WHEN WE HAVE RIGHT NOW IN THE OVERALL PROGRAM, THESE ARE THE OVERALL NUMBERS, IF YOU SEE WE COMBINE THE DCGE, WHICH IS A SMALL SMALL INTRAMURAL BUT A SMALL INTRAMURAL, BUT WE SEE THE DIVISION WHERE WE HAVE CLINICAL AND INVESTIGATORS, AND BASIC 124, BUT THIS GIVES THE OVERALL SPREAD. AND THE POINT WE MADE WAS THAT WE'VE REDUCED OUR STAFF BY 18% BY 375 ABOUT 12 YEARS AGO TO A CURRENT NUMBER OF 307. SO THAT WAS MAINLY DUE TO DEPARTURES AND NOT REFILLING ALL OF THOSE DEPARTED SLOTS. WE'VE HAD REALLY ACTIVE ENGAGEMENT WITH OUR PROCESS THROUGH BSC, AS I MENTIONED. CAN YOU SEE THAT OUR INTRAMURAL INVESTIGATORS ARE A--DISTINGUISHED GROUP. WE HAVE EIGHT MEMBERS, NINE MEMBERS OF THE NATIONAL ACADEMY. 11 MEMBERS OF THE INSTITUTE OF MEDICINE, YOU KNOW 17 MEMBERS OF THE AAP, MEMBERS OF ASCP, ET CETERA, SO WE HAVE A LOT OF RECOGNIZED BOTH SENIOR AND JUNIOR INVESTIGATORS FOR THEIR RECOGNIZED FOR THEIR DISTINCT SCHOLARSHIP. SO SOME OF THE DISTINCTIVE FEATURES OF OUR INTRAMURAL PROGRAM IS THAT WE'RE ALMOST 30% OF ALL THE INTRAMURAL RESEARCH PROGRAM SO WE'RE THE LARGEST WHICH OF COURSE GIVES US A BREDTH AND DEPTH OF INTERDISCIPLINARY SCIENCE SPANNING FROM BASIC BIOLOGY TO CLINICAL TRIALS, AND REALLY IN THE DCEG, THE LARGEST INTRAMURAL RESEARCH POPULATION SCIENCE EFFORT. THE CULTURE OF THE CORRIDORS IS REALLY ALIVE HERE, THAT IS VERY CLOSE PROXIMITY BETWEEN BASIC AND CLINICAL RESEARCHERS. THAT'S DONE ON PURPOSE. THAT WAS DESIGNED THAT WAY. AND I THINK THE NCI HAS HAD A DISPROPORTIONATE COMMITMENT TO PATIENT BASED SCIENCE THAT REALLY IS HIGHLIGHTED BY THE FACT THAT WE'RE AROUND 37% OF ALL THE CLINICAL ACTIVITY WITHIN THE NCI CLINICAL CENTER. WHICH REALLY IS A UNIQUE THING, AND ALLOW UNCOMMON ABILITY TO PERFORM MECHANISTIC STUDIES IN PATIENTS WITH CANCER. AND WE HAVE A VERY CLOSE RELATIONSHIP WITH THE FED RICK NATIONAL LABORATORIES. SOME OF THE OTHER DISTINCT FEATURE SYSTEM THAT WE CAN COMMIT TO LONG-TERM PROJECTS THAT WOULD OFTEN BE DIFFICULT TO SUSTAIN BY EXTRAMURAL FUNDING MECHANISMS AND I THINK WE OFTEN HIGHLIGHT DOUG LOWY AND JOHN SCHILLER'S ABILITY TO WORK SO LONG ON THESE VIRAL REGULATED PARTICLES THAT ULTIMATELY LED FOR A VACCINE FOR HPV, AND THAT WAS A MULTI, MULTIYEAR AND THE FIRST FEW YEARS WERE VERY HARD TO GET FUNDED BECAUSE IT WAS A TOUGH ROAD EARLY ON. THERE'S A STRONG COMMITMENT AND YOU'LL SEE THIS, I SEE THIS, AND STRONG COMMITMENT RARE DISEASES DISPROPORTIONATELY UNDERSERVED PATIENT POPULATIONS AND COMMITMENT IN THE EPIDEMIO LOGIC ABILITY THAT IT WORKS ON. SOME OF OUR PAST ACHIEVEMENTS INCLUDE MULTIPLE FDA APPROVED DRUGS FOR BOTH CANCER AND HIV AS I JUST MENTIONED, WE ARE DEVELOPED TECHNOLOGY HERE TO ENABLE THE HPV VACCINE. A LOT OF CONTRIBUTIONS TO UNDERSTANDING AND EXTREME OF RARE CANCERS. OBVIOUSLY WE'VE BEEN IN THE FIELD OF ADOPTED IMMUNOTHERAPY BEFORE IT WAS THE NEXT NEW THING AND THAT'S BEEN A LONG-TERM COMMITMENT AND I THINK WE'RE REALLY STARTING TO SEE FRUIT. RECENTLY THE GROUP HERE WORKING ON PROSTATE CANCER LED TO THE DEVELOPMENT OF TECHNOLOGY NEAR IMAGING AND PROSTATE CANCER AND SEVERAL OTHER NOTABLE CONTRIBUTIONS ARE LISTED BELOW INCLUDING NOVEL INN SIGHT INTO'S TARGETED INTERVENTIONS FOR LYMPHOMA. THE IDENTIFICATION OF GENERATEDET INCREASE IN BODY SUSCEPTIBILITY OF SEVERAL SUBTYPES OF KIDNEY CANCER, CHROMATIN STRUCTURE AND OBVIOUSLY REGULATION AND HARNESS OF THE IMMUNE SYSTEM. SO WE HAVE DONE SEVERAL THINGS TO TRY TO CREATE OPPORTUNITIES WITHIN OUR LIMITED BUDGET TO FREE UP A LITTLE BIT OF MONEY FOR PEOPLE TO DO SOME CREATIVE THINGS. WE CREATED A MAJOR OPPORTUNITIES PROGRAM THAT WAS COMPETITIVE AND THREE--AND IT WAS ACTUALLY VOTED ON BY OUR WHOLE INTRANSLATIONAL RESEARCH MURAL INVESTIGATORS AND WE CHOSE INITIALLY THREE ONGOING PROGECS AND THESE ARE LIMITED THREE-FIVE YEAR PROJECTS, ONE WAS A DRUG SCREENING PROJECT. ONE WAS A PROJECT TO BE ABLE TO IMAGE METABOLIC DERANGEMENTS AND CANCER AND A THIRD WAS CHROMATIN PROFILING. THE PROJECTS WERE DESIGNED TO TRY TO ACCELERATE NOVEL APPROACHED. WE ALSO DEVELOPED A TUMOR REPAIR THAT WASN'T READY FOR MAJOR OPPORTUNITIES BUT WE DID CREATE THE INITIATIVE TO APPLY NCI EXPERTISE BOTH IN BASIC AND CLINICAL STUDIES AND WE FOCUSED ON DEZ MOID TUMORS AND PLEXA FORM NEUROFIB ROMAS AND IT WAS LED OUT OF DR. KUMAR, AND I HIGHLIGHT IN BLUE, RARE TUMORS AND WE MOST RECENTLY JUST MADE A CALL FOR WHAT WE CALL FLEXIBILITY FUNDING PROGRAMS. THIS IS ANOTHER SERIES OF COMPETITIVE PROGRAMS. THIS WILL BE LED BY A GROUP THAT INCLUDES INTRAMURAL AND EXTRAMURAL INVESTIGATORS AND SPANS SEVERAL INSTITUTES, NOT JUST THE NCI. WE HAVE SEVERAL AREAS OF DEVELOPMENT TECHNOLOGY DEVELOPMENT, A SIN KNOWLEDGEY AWARD AND THE IDEA IS TO BRING ACROSS BRANCHES THAT ARBITRATE CURRENTLY COLLABORATING TO SOLVE A PROBLEM AND A NEW DIRECTIONS PROGRAM WHICH IS MORE SOMETHING THAT HASN'T BEEN DONE YET, FOR THE OPPORTUNITY. WE JUST SENT OUT THE CALL, THE APPLICATIONS ARE DUE IN DECEMBER AND AND WE HOPE TO MAKE AWARDS AND WE SET ASIDE MONEY FOR THIS PROGRAM. SO IN THE LAST FEW MINUTES, I WANT TO FOCUS ON OUR RESEARCH PRIORITIES AND THAT'S WHERE I WOULD LIKE TO LEAD THE DISCUSSION AND THAT IS TO DESIGN AND EXCUED NOVEL SCIENCE BASED CLINICAL TRIALS. SO LIKE ALL OF YOUR INSTITUTES WE WOULD LIKE TO FOCUS ON MOLECULAR BASEDDED TAILORED MEDICINE. CERTAINLY WE WANT TO UTILIZE THE TECHNOLOGY AND CORRELATIVE SCIENCE THAT'S DIFFICULT TO SUPPORT AND OBVIOUS EXAMPLE OF THAT IS OUR ABILITY TO PUT A HEAVY FOCUS ON IMAGINGLY AND OUR CLINICAL TRIALS. BUT ALSO WE'RE VERY--WE IS A MISSION TO FOSTER THE EDUCATION OF RESEARCH AND PHYSICIAN SCIENTISTS. OBVIOUSLY WE NEED AS MUCH SUPPORT IN MY OPINION FOR THAT GROUP AND WE'RE PREPARED TO CONTINUE TO WORK ON THAT. AND AGAIN STUDY RARE CANCERS. THAT SHOULD BE IN BLUE AGAIN. SO WHEN WE LOOK AT OUR AREA OF STRENGTH, I DON'T HAVE TO REITERATE THESE, SO WE CAME UP WITH THESE SORT OF SEVEN OR EIGHT YEARS OF SPRENTH. IMMUNOTHERAPY, LYMPHOMA, PEDIATRIC MALIGNES BUT RARE CANCERS WAS OBVIOUSLY AN AREA OF STRENGTH AND WE WOULD LIKE TO EXPLORE THE ABILITY TO DO MORE OF THAT. WE'VE DONE A LOT OF REENGINEERING AND SO I APOLOGIZE FOR THOSE OF YOU THAT HEARD THAT BUT OVER THE LAST COUPLE YEARS WE'VE HAD MAJOR REORGANIZATION IN OUR LABS AND BRANCHES AND WE CREATED A MEDICAL ONCOLOGY CLINICAL SERVICE THAT GOES ACROSS ALL OF THE--ALL OF THE CLINICAL OPPORTUNITIES. WE--DRAMATICALLY CHANGE THE WAY PROTOCOL CONCEPTS ARE REVIEWED AND THEY'RE REVIEWED ACROSS THE ENTIRE INTRAMURAL CCR NOW. WE'VE SUCCEEDED IN ACCELERATING THE TIMELINE WHERE FOR 90 DAYS NOW, WE'D LIKE TO GET IT TO 60 SO WE HAVEN'T LOST SITE OF THAT GOAL BUT WE'VE GONE FROM 160 TO 90 DAYS AND WE CREATED A PROTOCOL SUPPORT OFFICE THAT'S BEEN HELPFUL IN ALLOWING INVESTIGATORS FROM FIELDS THAT MAY NOT NECESSARILY HAVE CLINICAL EXPERTISE BUT HAVE GOOD IDEAS TO PARTNER WITH CLINICAL INVESTIGATORS BUT ALSO TO HELP GET PROTOCOLS WRITTEN. BUT WE WANT TO LOOK AT NEW SCIENTIFIC OPPORTUNITIES. WE OPEN THIS UP TO OUR ENTIRE INTRAMURAL PROGRAM AND WE RECEIVED 30 PROPOSALS. WE HAVE A CCR SCIENCE BOARD THAT WE CREATED THAT'S CHAIRED BY TOM MASTELLI, AND IN THAT GROUP, PICKED FIVE PROPOSALS FOR FURTHER CONSIDERATION AND THOSE FIVE PROPOSALS ARE LISTED BELOW. AND ALL INTERESTINGLY WHEN WE SENT THIS DRAFT IN, ALL FIVE OF THOSE PRECISION MEDICINE CELL BASED THERAPIES HUMAN MICROBIOME, NATURAL PRODUCT THE HUMAN RNA PROJECT WERE ALL LIST INDEED THE CONSOLIDATED REPORT SO THIS RANG TRUE WITH OTHER MULTIPLE INSTITUTES AS WELL. SO JUST QUICKLY, THE PRECISION MEDICINE AND PREVENTION IS TO DEVELOP STRATEGIES STAY LORA RODRIGUEZED TO EARLY PEDIATRIC AND RARE CANCERS AS WELL AS SEVERAL TUMOR TYPES ALREADY PROMULGATEINANTLY FEATURED AS I SHOWED YOU ON A PREVIOUS SLIDE. AGAIN RARE CANCER SYSTEM COMING UP AND TO EXPLORE ACCESS TO THE WELL CHARACTERIZED PATIENT POPULATIONS, CERTAINLY THE AVAILABILITY OF MOLECULAR EPIDEMIOLOGIC DATA SETS: SO THOSE ARE A PROGRAM WITH DCEG WHICH WE HADN'T HAD BEFORE AND TO USE THE STRONG EXPERTISE IN MOLECULAR CANCER MECHANISMS ACROSS OUR BASIC LABS. SO YOU CAN SEE THE APPROACHES TO DEVELOP NEW CELL BASED THERAPIES, COMBINING CELL BASED ENGINEERING AND IMMUNO BIOLOGY AND THE GOALS ARE LISTED THERE. OBVIOUSLY WE WOULD VERY MUCH LIKE TO ESTABLISH THE INFRASTRUCTURE FOR DISSEMINATION OF THESE IF WE COULD AND TO FOCUS ON APPROACHES AND DISEASE TYPES THAT ARE NOT DESIRABLE FOR CURRENT BUSINESS PLANS. THIS IS A BIG PROBLEM I THINK ACROSS MANY INSTITUTIONS. THE HUMAN METAORGANISM AND CANCER BIOLOGY AND MEDICINE IS OBVIOUSLY THE MICRO BIOME, THERE'S BEEN TWO ARTICLES IN THE NEW YORK TIMES OVER THE LAST MONTH. THIS IS AN EXPANDING AREA. WE KNOW MORE AND MORE THAT THE MICROBIOME INFLUENCES BOTH THE HANDLE BEING OF DRUGS AS WELL--HANDLING OF DRUGS AS WELL AS IMMUNOLOGIC RESPONSE SO THE GOAL IS TO MAP THE MICRO BIOME ON HEALTH AND DISEASE AND INFLAMMATION, SIGNALING AND IMMUNE FUNCTION AND UNDERSTAND HOW IT EFFECTS CANCER TREATMENT. THE NATURAL PRODUCTS PROGRAM WAS A PROPOSAL TO CONTRIBUTE TO A NATIONAL PROGRAM FOR NATURAL PRODUCTS DISCOVERY FOR NEW MOLECULES THAT TARGET BIOLOGIC PROCESSES, CENTRAL TO HUMAN DISEASE AND THE GOALS ARE LISTED HERE AND WE REALLY WANT TO DEVELOP A COMPREHENSIVE LIBRARY THAT INCLUDES PREFRACTIONATED COMPOUNDS WHICH INCLUDE ABOUT A MILLION FOR MODERN HIGH THROUGH PUT TARGETED SCREENING PROGRAM AS MOST OF YOU KNOW, NATURAL PRODUCT VS BEEN ABANDONED BY THE PHARMACEUTICAL INDUSTRIES BECAUSE IT'S TOUGH. SO WE FEEL WE CAN REALLY PROVIDE A NATURAL RESOURCE AND TAKEN--THEY'S REALLY THE LAST BULLET HERE FOR ASSAY DEVELOPMENT, EXECUTION OF DRUG SCREENS, WE SUPPLY ACTIVE MOLECULES AND BIOINFORMATICS FOR EXTRAMURAL SUPPORT FOR EXTRAMURAL USERS. LAST BUT NOT LEAST IS A HUMAN RNA PROJECT. AND THIS IS TO EVALUATE COMPREHENSIVE PROGRAM FOR THE INVESTIGATION AND THERAPEUTIC EXPLOITATION OF RNA AND WE ALL KNOW THIS IS IN ITS INFANCY BUT THERE ARE OPPORTUNITIES TO USE RNA FOR THERAPEUTIC PURPOSES AND THE GOALS ARE SORT OF AGAIN LISTED HERE, VERY AMBITIOUS. SO WHAT ARE OUR NEXT STEPS? SO EACH OF THOSE FIVE PROGRAMS OF CCRs PLANNING A SERIES OF WORKSHOPS AND WE'RE VERY INTERESTED AND VERY MUCH GOING TO INCLUDE EXTRAMURAL EXPERTS IN THIS, WE WILL ALSO INCLUDE EXPERTS FROM OTHER INSTITUTES IF THAT'S POSSIBILITY. SO FOR EXAMPLE IN THE MICRO BIOME PROJECT, NIAID HAS A ROBUST PROGRAM AND WE WILL INVITE INVESTIGATORS FROM NIAID, INTERESTINGLY IN THE RNA PROGRAM WHEN I PRESENTED THIS TO THE NCAB, TYLER JACKSON IS VERY EXCITED. HE SAID THEY'VE BEEN TALKING ABOUT RNA'S THERAPEUTIC AND THERE'S CLEARLY AN INTEREST IN HIS INSTITUTE TO PARTICIPATE IN THAT. AND BUT WHAT I--WHEY REALLY THINK IS ONE OF THE OTHER AREAS THAT WE WOULD VERY MUCH LIKE TO EXPLOIT IS THE OPPORTUNITY TO PARTNER WITH THE EXTRAMURAL PROGRAM, NOT JUST IN THE OTHER PROJECTS BUT SPECIFICALLY FOCUSED ON FOLK US ON RARE TUMORS. AND THAT WOULD BE INVOLVED IN ENGAGING THE EXTRAMURAL COMMUNITY IN A PRECISION MEDICINE WORKSHOP. ALL OF US KNOW AND PART OF THIS WAS ALSO PRECIPITATED BY HAROLD VARMUS MENTIONED TO ME THE COOPERATIVE GROUP CHAIRS, THERE WAS DISCUSSION ABOUT LESS THAN DESIRABLE INTERACTION WITH THE INTRAMURAL PROGRAM. I WASN'T SURE WHAT THAT ENTAILED BUT WHEN WE THOUGHT ABOUT IT, ALL THE COOPERATIVE GROUPS HAVE THE INITIATIVE BUT IT'S HARD TO STUDY RARE TUMORS AND ONE OF THE THINGS WE DO HAVE THE ABILITY TO DO HERE IS TRAVEL PATIENTS FROM ALL OVER THE COUNTRY, AND THAT'S WHY WE'VE BEEN SUCCESSFUL FOR EXAMPLE, THE DESMOID INITIATIVE, GIOVANI WROTE A STUDY USING A GAMMA [INDISCERNIBLE] ACTIVITY BECAUSE OF A POSTER WE SAW A FEW YEARS AGO AT ASCO AND WE THOUGHT IT WOULD TAKE TWO OR THREE YEARS TO DO THE STUDY AND IT WAS DONE IN A YEAR. BECAUSE ONCE PATIENTS HEARD ABOUT IT WE COULD BRING THEM IN FROM ALL OVER THE COUNTRY. SO THAT'S WORTH A DISCUSSION AND OBVIOUSLY ANY OTHER OPPORTUNITIES ACROSS THESE INITIATIVES WE WELCOME INTERACTION WITH THE EXTRAMURAL COMMUNITY. SO I'LL STOP THERE. >> THANK YOU, I WOULD LIKE TO INVITE LOU WEINER, IF YOU HAVE REMARKS FROM THE LONG-TERM PLANNING COMMITTEE. >> YES, THANK YOU, JIM. THIS WAS A REMARKABLE EXPERIENCE FOR ALL OF US THAT PARTICIPATE INDEED IT. I THINK THE IMPORTANT THING TO NOTE IS THAT THE EMPHASIS THAT WAS APPLIED BY LEE AND THE RECOLLECT INTRAMURAL PROGRAM LEADERS WITH OUR ENCOURAGEMENT WAS TO CAPITALIZE ON THOSE ATTRIBUTES OF INTRAMURAL PROGRAM THAT WAS DISTINCTIVE THAT COULDN'T BE EASILY REPLICATED. I THINK THERE WAS AN UNDERSTANDING THAT NO ONE INSTITUTION CAN DO THINGS THAT ARE COMPLETELY IMPOSSIBLE EVERYWHERE ELSE, BUT THERE ARE DISTINCTIVE CAPABILITIES THAT EXISTED AT THE INTRAMURAL PROGRAM NOT THE LEAST OF WHICH WAS THE ACCESS TO THE OTHER--STRENGTHS OF OTHER INTRAMURAL PROGRAMS OUTSIDE OF NCI THAT COULD BE EXPLOITED BUT THE 5-AREAS THAT WERE TARGETED EXEMPLIFIED EXCITING NEW AREAS WHERE IT WOULD BE GOOD TO ADDRESS THESE EASILY AND WHERE, NOT ONLY WOULD THERE BE NOVEL SCIENTIFIC OPPORTUNITIES BUT IN SOME CASES, NOVEL TOOLS THAT COULD BE DEVELOPED FOR EXAMPLE, THE NATURAL AND MENTAL COMPOUND THAT'S BEING DISCUSSED REALLY IS AN EFFORT THAT DOESN'T REALLY EXIST AS FAR AS KNOWN IN THE INDUSTRY ON A BROAD SCALE IS A GREAT OPPORTUNITY TO LEVERAGE UNIQUE RESOURCES. SO ONE OF THE OTHER THING WE CONSIDERED AND DIDN'T GET EMBEDDED FULLY INTO THIS REPORT I WAS HOW TO HARMONIZE THE FUNCTION AND THE ORIENTATION OF THE CLINICAL CENTER IN ORDER TO BE ABLE TO ACCOMMODATE THESE CHANGES AS WE MOVE FORWARD, IN OTHER WORDS AS THE INSTITUTES PRIORITIES CHANGE. AS CERTAIN AREAS BECOME EMPHASIZED WILL THE CLINICAL CENTER HAVE THE FLEXIBILITY AND THE TO ACTUALLY CHANGE WHAT IT OFFERS AND WHAT THE SKILL SETS ARE IN ORDER TO BE ABLE TO ACCOMMODATE THESE CHANGES AND I THINK THAT TO MY KNOWLEDGE, AND LEE YOU CAN CORRECT ME IF I'M WRONG, I THINK THAT'S STILL UNDER-- >> I KIND OF LEFT IT OUT BECAUSE IT'S SUCH A BIG TOPIC AND OBVIOUSLY. >> YEAH, IT IS A BIG TOPIC. I MENTION IT, BUT I THINK WE COULD GET BOGGED DOWN IN A DISCUSSION THAT MAY NOT BE THE MOST APPROPRIATE AT THIS TIME FOR THIS GROUP. BUT IT IS A BILGE ISSUE THAT'S BEING DISCUSSED ALL THE INSTITUTE DIRECTORS ARE VERY ENGAGED IN THAT. I SHOULD SAY MAYBE THESE NEW UO-ONE MECHANISMS THAT WERE ON OUR THIRD ONE, I THINK THAT ARE ENCOURAGING INTRAMURAL, EXTRAMURAL COLLABORATIONS WHERE EXTRAMURAL INVESTIGATORS THAT HAVE SPECIFIC QUESTIONS THAT MIGHT BE ABLE TO UTILIZE THE CLINICAL CENTER. WE HAD THREE THAT WE FUNDED IN THE FIRST CALL AND THESE ARE REVIEWED BY THE--BY THE EXTRAMURAL REVIEW PANEL. BUT, WE'RE TRYING TO EXPLORE THOSE KINDS OF MECHANISMS AS WELL. >> TWO COMMENTS. FIRST THE CONSULTANTS OF THIS PROCESS WERE MINDFUL AND APPRECIATIVE OF THE OPPORTUNITIES TO CREATE THESE INTRAMURAL AND EXTRAMURAL COLLABORATIONS AND WE WANT TO ENCOURAGE THAT IN AND WAY POSSIBLE. THE SECOND IS THAT LEE MENTIONED THERE'S BEEN A SIGNIFICANT CONSTRAIKS OF THE MINCE PEL INVESTIGATOR POOL IN THE INTRAMURAL PROGRAM AT THE NCI OVER THE PAST NUMBER OF YEARS AND THIS HAS CREATED OPPORTUNITIES TO THINK ABOUT WAYS TO REFOCUS THE SCIENTIFIC EMPHASIS AND WE THOUGHT THESE FIVE AREAS REPRESENTED REALLY GOOD ORGANIZING PRINCIPLES WHO WERE HELPING TO RETHINK HOW WE'RE GOING TO ORGANIZE INTRAMURAL PROGRAM RESEARCH AS TIME MOVES ON, SO THIS HAS A LOT OF SUPPORT FROM THE--BOTH THE CLINICAL EPIDEMIOLOGY ANDA ALSO THE BASIC ESC FOR THAT REASON. I'LL STOP THERE. >> THANK YOU. >> I THINK YOU DID AN EXCELLENT POINT OF THE INTERNATIONAL CLASSIFICATION MA MURAL ACTIVITIES THAT OCCUROT CAMPUSES BUT THIS IS SOMETHING I WAS THINKING ABOUT BUT I DONE KNOW IF THE INTRAMURAL PROGRAM GETS CREDIT FOR BUT THE TRAINING BUT BEING AN INCUBATOR FOR DIFFERENT PROGRAMS AND ACTING LIKE TENURE IN THE 90S AND THERE ARE MANY SITUATIONS WHERE I CAN THINK OF RESEARCH, WHOLE GROUPS THAT HAVE THEIR ORIGIN HERE AND THEN MOVE TO THE EXTRAMURAL COMMUNITY AND THRIVE THERE. SO DAVE POPLECK, AND THE GROUP TEXAS CHILDRENS HAD THEIR CORE HERE, THE NAVY GROUP AT THE HOSPITAL, U. T. SOUTHWESTERN AND THEN I WAS THINKING ABOUT THIS AGAIN WHEN I WEPT TO THE SOCIETY FOR IMMUNOTHERAPY FOR LAST WEEK YOU HAD WALTER ERVA, AND PART OF THE RESPONSE MODIFIER GROUP UP AT FREDERICK, THEY'RE KIND OF THE CORE FOR THE STUDENT IN OREGON. WHEN I WAS HERE AT NCI AND THE BIG GROUPS LEFT, WE SAW IT AS A NEGATIVE BECAUSE WE SAW IT AS SUBTRACTION. BUT NOW FROM THIS PERSPECTIVE, IN MANY WAYS THESE RESEARCH GROUPS INCUBATED HERE, MOVED TO THE EXTRAMURAL COMMUNITY AND THEN DRIVED THERE BUT THEY HAD KIND OF THEIR ORIGIN HERE AND I THINK THAT'S SOMETHING THAT'S INCREDIBLY VALUABLE. I DON'T KNOW HOW YOU CAPTURE THAT BUT-- >> YEAH, THANK YOU, CHRIS. WE'VE HAD A LOT OF DISCUSSION ABOUT THAT. AND I DO THINK THERE ARE EXAMPLES OF YOU KNOW MANY HEADS OF DEPARTMENT, MANY COOPERATIVE GROUPS HAVE SO I THINK IT IS--I THINK WE DO A GOOD JOB AND WE VALUE THAT AND WE CONTINUE AND WE WANT TO CONTINUE TO TO PUT A LOT OF EMPHASIS ON TRAINING BUT I DO THINK IT IS AN AREA WHERE WE ARE--NOT UNIQUELY SUCCESSFUL BUT QUITE SUCCESSFUL AND WE FEEL WE HAVE A SIGNIFICANT ROLE TO PLAY. >> DID YOU HAVE A COMMENT. >> YES, VERY POWERFUL PRESENTATION, A GREAT DEAL. AND I WAS ALSO VERY PLEASED TO SEE YOU PLACING EMPHASIS ON THE COMMITMENT NOT ONLY TO STUDY RARE DECEASES BUT DISEASES PROPORTIONATELY SERVING ORBED SERVED POPULATIONS AND I WONDER IF YOU WOULDN'T MIND EXPANDING ON THAT A LITTLE BIT? >> WELL, YOU KNOW I THINK THERE WAS NO QUESTION THAT MINORITY POPULATIONS IN GENERAL FAIR MORE POORLY AND OUTCOME OF ANY OF THESE AND THERE ARE A VARIETY OF REASONS BOTH GENETIC AND ECONOMIC AND THEY'VE BEEN BEEN A LOT OF TRASH IN THE AIR ABOUT THIS BUT THESE POPULATIONS DESERVE NOR INTENSIVE STUDY, WE HAVE AN INVESTIGATOR, KEVIN GARNER HAS BEEN EXTREMELY INTERESTED IN THE BREAST CANCER AND POPULATION OUTCOMES, MOST SPECIFICALLY AFRICAN AMERICANS, WE FEEL THIS IS IMPORTANT AND SO DOES THE REST OF THE WORLD BUT WE FEEL WE COULD PLAY A SUBSTANTIAL ROLE AS A CATALYST TO REALLY SPAN THAT. AND SO WE'RE WORKING ON THAT AND IN FACT, IT JUST SO HAPPENED I HAVE AN E-MAIL. I HOOKED KEVIN UP WITH THE EXTRA MURAL APPLY FOR UR ONE USING THE CLINICAL CENTER SPECIFICALLY TO STUDY AFRICAN AMERICAN BREAST CANCER POOR PROGNOSIS AND TRY TO GET A HANDLE ON HOW MUCH IS ECONOMIC AND HOW MUCH IS GENETIC AND WHAT CAN WE DO ABOUT IT AND YOU KNOW THERE ARE--WE CAN DEAL WITH ALL OF THOSE. AND ESPECIALLY PARTNERING WITH DCEG, WE CAN FIND RECOMMENDATIONS THAT MAY HELP. SO WE'RE PRETTY COMMITTED TO THAT. >> KURT? >> I HAD TWO QUESTIONS, LEE, THIS IS GREAT LEE, AND LOU, THE FIRST WAS A DETAIL. I WAS SURPRISED YOU DIDN'T MENTION RESISTANCE AS A CO-AREA OF PRECISION MEDICINE THERAPIES THE MORE CANCER WITH QUICK RESISTANCE AND SCREENING FOR RESISTANCE MECHANISMS AND ACTUAL RESISTANCE IS MULTIPLEA MORE--MORE EBBS PENSIVE AND RESOURCE INTENSIVE THAN THE INITIAL SCREENS, YOU KNOW? THAT WOULD BE INTERESTING FROM OUR PERSPECTIVE EVERYONE'S LOOKING AT RESISTANCE MECHANISMS WE ALL UNDERSTAND THE PROBLEMS WE ALL UNDERSTAND THE DIVERSITY OF SUBCLONES THAT END UP KILLING THE PATIENT. SO WE DO FEEL THIS IS AN IMPORTANT QUESTION. WE WEREN'T SURE WE HAD SOME LEVERAGE OVER AND ABOVE WHAT WERE BEING DONE AT MULTIPLE TERRIFIC CENTERS BUT IF THERE ARE ISSUES THAT COULD BE DISCUSSED WE WOULD BE TOTALLY OPEN TO HOW WE WE MEANING THE INTRAMURAL PROGRAM COULD HELP IN THAT EFFORT, WE BEING THE CLINIC, IT WAS JUST WASN'T IN OUR INITIAL DISCUSSIONS. >> I WOULD THINK THE ABILITY TO DO THE GENETIC SCREENS ON THE LARGE SCALE AND THE CELL BASE SCREENS WE TALK ABOUT LATER IN THE DAY WOULD BE AN AREA FOR MY SECOND COMMENT, THE ULONES AND THE USE OF THE CLINICAL CENTER BY THE EXTRAMURAL COMMUNITY MY IMPRESSION IT'S BEEN UNDERWHELMING THE USE AND I'VE BEEN REALLY SURPRISED AT THAT. >> YEAH. >> GO AHEAD, LOU. >> I WANT TO DISCUSS THE RESISTANCE DISCUSSION, THAT WAS A TOP THAT I CAN WAS PRIORITIZED LOWER PRIMARILY BECAUSE IT DIDN'T RISE TO THE LEVEL OF THERE BEING UNIQUE NCI BAND WIDTH OR PERSPECTIVE THAT WOULD DIFFERENTIATE IT FROM A LOT OF THE OTHER WORK THAT'S BEING DONE IN THE EXTRAMURAL COMMUNITY AND IT WAS FELT THAT IT COULD BE INCORPORATED INTO A PRECISION MEDICINE KIND OF APPROACH WITH THE NOGS THAT ONE WOULD NOT BE LOOKING AT SIMPLY AT TRYING TO IDENNIFY THE RIGHT DRUG FOR THE RIGHT PERSON AT THE RIGHT TIME BUT PERHAPS THEERATE COMBINATION OF DRUGS, SO IT'S EMBEDDED WITHIN THE CONCEPT AND I THINK THE EXTERNAL ADVISORS AT LEAST FELT COMFORTABLE THAT THEY WOULD AKOCHLISH IT FOR THE PURPOSES OF THIS WORK EFFORT >> YEAH, IN TERMS OF THE ONE, I AGREE THERE WAS A LOT OF CONFUSION. IT WASN'T AS CRISPLY DEFINED AS IT SHOULD HAVE BEEN. THAT'S MY OWN OPINION, I'M NOT SPEAKING ON BEHALF OF THE INTUITY IN ANY WAY SHAPE OR FORM. AND THERE WERE A LOT OF A LOT OF ISSUES TO BE RESOLVED SO THE HOPE IS THAT AS IT MATURES TELL BE CLEARER TO PEOPLE. THERE WERE APPLICATIONS THAT JUST WANTED TO--NOT USE THE CLINICAL CENTER, BUT TO DO TESTS SO THERE WAS CONFUSION, I DON'T THINK IT WAS AS CLEARLY DEFINED AS IT MAYBE COULD HAVE BEEN. AS I SAID, WE FUNDED THE MOST. I THINK WE FUNDED THREE. I MEAN PAULET'S GROUP DID THE REVIEWS AND AT LEAST ONE OF THEM IS DRIVING AND DOG QUITE WELL. I DON'T KNOW ABOUT THE OTHER TWO, I HAPPENED TO TALK TO ONE OF THEM ON FRIDAY, I CONTINUING HAD GROWING PAINS AND I THINK WE'LL HAVE TO SEE WHAT HAPPENS WITH THE NEXT ROUND. >> SO HIGHLIGHTING OR ELUCIDATING AN APPROPRIATE SUCCESS STORY MIGHT BE-- >> YEAH, IT'S A GOOD IDEA. >> SO LEE THANK YOU. I THINK IT'S SAFE TO SAY MOST EXTRAMURAL INVESTIGATORS REALLY DON'T UNDERSTAND THEIR INTRAMURAL PROGRAM OR HOW TO WORK WITH IT AND I CAN THINK OF A COUPLE WAYS THAT MAYBE WE CAN CHANGE THAT, NUMBER ONE IS WITH REDESIGNED EVENT AND THE NCI WEBPAGE HAVE A DEDICATED PAGE THAT SAYS UNDERSTANDING INTRAMURAL PROGRAM FOR EXTRAMURAL-- >> IT'S INTERESTING YOU SAY THAT BECAUSE THAT IS ONE OF THE THINGS, I MEAN PETER MENTIONED THAT, WE WERE LEFT OFF THE NCI CORPORATE PAGE--IT WAS FELT, WELL WE CAN'T ADVERTISE IN THE INTRAMURAL PROGRAM BUT HOPEFULLY WE CAN DO THAT WITH PETER'S REENGINEERING. >> THE OTHER IS THE ASSOCIATION FOR AMERICAN CANCER ASSOCIATES WILL BE IN WASHINGTON. WHY DON'T WE PLAN ON HAVING A SESSION DEDICATED TO LOOKING AT COLLABORATIONS BETWEEN INTRAMURAL AND EXTRAMURAL PROGRAMS. >> THAT WOULD BE AWESOME. THAT WOULD BE FANTASTIC. >> IT WAS ONE OF OUR SHINING EXAMPLES OF TOOK HER FANTASTIC TALENTS EXTRAMURALLY. WE'RE VERY PROUD OF YOU NANCY. >> THANK YOU VERY MUCH. >> I'M ONE OF SEVERAL AROUND THE TABLE, I HEAR. THAT WAS A REALLY NICE REPORT IF I GO BACK TO WHERE YOU STARTED THIS IS THE NCI EFFORT IS THERE WERE PARALLEL EFFORTS WITH ALL YOUR SISTER INSTITUTES AND CENTERS AND SO WHAT DO YOU THINK WILL ENEMY YEAR AND HOW SPECIFIC DETAILS ON YOU SEE THIS WILL ROLL UP TO THE WHOLE VISION OF THE NIH. >> WELL, EVERYONE IS CURIOUS ABOUT THIS AND IN FACT WE ASKED HAROLD BECAUSE WE FIGURED, IT'S TOTALLY UNCLEAR TO US WHAT I MEAN I THINK WE'LL HAVE A BETTER SENSE AFTER THE AC--THE ACD COMMITTEE IN DECEMBER 12th I BELIEVE IT IS, SO IT'S NOT CLEAR TO US WHAT THEY'RE GOING TO FOCUS ON. I THINK THAT OUR ATTITUDE AND CERTAINLY IN DISCUSSING THIS WITH HAROLD IS GERONTOLOGYSTS GARDLESS OF WHAT COMES OUT FOR THE GLOBAL NIH, WE FELT THIS WAS AN OPPORTUNITY WE COULD TAKE ADVANTAGE OF TO REFOCUS AND PRIORITIZE CERTAIN THINGS AND I THINK JUST FOR THAT, HOPEFULLY IF WE CAN BE SUCCESSFUL WE WILL HAVE GAINED SOMETHING BUT THE GLOBAL ISSUE IS, IT'S REALLY AN ENIGMA TO US. WE'RE NOT EXACTLY--WE KEEP HEARING, IT'S ALL ABOUT THE CLINICAL VIT'S ABOUT THIS, AND SO IT'S VERY UNCLEAR, IT WAS VERY UNCLEAR TO US WHEN FRANCIS FIRST CAME WITH THE CHARGE. WHAT EXACTLY HE WAS LOOKING FOR AND I STILL HAVEN'T HEARD A CONCISE ANSWER TO THAT. >> THANK YOU DR. HELMAN FOR THIS PROCESS. AS THE PLANNING CONTINUES AND THE PROGRAM BETWEEN THE INTRAMURAL AND EXTRAMURAL PROGRAM EVOLVES WHAT SHOULD THE PATIENT AND THE COMMUNITY KNOW HERE WHAT IS THE TAKE HOME MESSAGE FOR THE PATIENT COMMUNITY AND THIS PROCESS? >> WELL, I HOPE WITH THE PATIENT COMMUNITY CAN GET OUT OF THIS IS THAT WE ARE A PART OF THE NCI'S EFFORT AND WE DO--AND THAT INCLUDES PATIENT CARE. AND SOMETIMES I THINK THERE'S A MISCONCEPTION ABOUT THAT. AND SO I HOPE IT WILL JUST BE MORE APPARENT TO THE ADVOCACY COMMUNITIES THAT THE INTRAMURAL NCI IS PART OF THE OVERALL NCI EFFORT IN TRYING TO PUSH FORWARD IMPROVED OUTCOMES IN PATIENTS WITH CANCER. I DON'T KNOW THAT I CAN SAY MUCH MORE THAN THAT AND I THINK YOU'RE WELL AWARE OF THE INTRAMURAL PROGRAM BUT I THINK THIS IS AND RETOOLED ADVOCACY GROUP THAT HAROLD'S NOW PUT TOGETHER AGAIN. I THINK WE WILL BE PART OF THAT DISCUSSION. ALL WE CAN HOPE FOR IS AN AWARENESS THAT WE'RE PART OF THE EQUATION. >> LEE, I WONDER YOU MENTIONED A COUPLE OF SORT OF MECHANISMS BY WHICH THE INCREASED COLLABORATION WITH EXTRAMURAL INVESTIGATORS WOULD OCCUR THROUGH THE NCTN AND THE COOPERATIVE GROUPS AND THE UR ONE MECHANISM, ARE YOU THINKING OF WAYS ABOUT FOSTERING THESE RELATIONSHIPS OR PERHAPS WITH CANCER CENTERS OR SOME OTHER WAY OF ACCOMPLISHING ABOVE AND ABOVE WHAT YOU ALREADY GOT. SO JIM THE ANSWER IS YES, BUT WE NEED YOUR HELP, SO I THINK IF YOU HAVE IDEAS OR IF WE COULD HAVE A SUBCOMMITTEE TO TALK ABOUT THIS, WE'RE VERY OPEN. I THINK THAT WE REALLY SEE OURSELVES AS PART OF THE NATIONAL PROGRAM. WE CERTAINLY FEEL THAT THE CENTERS ARE A HUGE COMPONENT BUT WE FEEL WE CAN BE CONTRIBUTOR NEUROECTODERMAL PART OF THAT EFFORT AND HOW CAN DO THAT. YOU KNOW THERE ARE CERTAIN BARRIERS, YOU KNOW THERE'S A CLEAR BARRIER, YOU CAN'T MIX INTRAMURAL AND EXTRAMURAL BUT THERE ARE WAY WHAT'SY CAN BE CREATIVE AND GET MORE DONE BY LEVERAGING IF THERE ARE THINGS THAT THE EXTRAMURAL COMMUNITY BELIEVES WE CAN CONTRIBUTE IN A WAY THAT MAKES, THAT LOWERS, YOU KNOW THE ACTIVATION ENERG TOW SOLVE A PROBLEM, WE WOULD VERY MUCH LIKE TO FIGURE OUT HOW TO DO THAT. AND WHETHER IT'S--LIKE I SAID HAVING THESE WORKSHOPS WHERE WE BRING IN EXTRAMURAL--EXTRAMURAL FOLKS WE WILL DO THAT BUT I THINK--FIRST OF ALL I THINK THE IDEA OF GETTING TOGETHER WITH THE CANCER CENTERS IN THE SUMMER IS A FANTASTIC IDEA BUT I WOULD LOVE TO HAVE THE CHANCE TO FIGURE OUT OTHER WAYS WHERE WE CAN JUST BE SITTING AT THE TABLE TRYING TO SOLVE PROBLEMS WITH OUR--WITH THE REST OF THE COMMUNITY. SO MAYBE COMMENTS OR SENSE OF THE COMMITTEE AS FAR AS YOU KNOW IS THIS SOMETHING--I THINK THIS IS A GREAT OPPORTUNITY OBVIOUSLY TO TRY TO LEVERAGE THE INCREDIBLE RESOURCES THAT ARE BOTH INTELLECTUAL AND FINANCIAL AT THE INTRAMURAL GROUP. IS THIS SOMETHING THAT THE COMMITTE FEELS WE WANT TO TAKE SOME OWNERSHIP OF AND I HESITATE TO FORM MULTIPLE ADDITIONAL COMMITTEES THAT INVOLVE SMS CAREFUL CONSIDERATION BUT JUST TO GET A SENSE THIS AN AREA THAT PEOPLE FEEL STRONGLY, PASSIONATE ABOUT THAT CTEC COULD PLAY AN IMPORTANT MAYBE PROACTIVE ROLE FOR--AROUND SOMETHING LIKE THIS. IS THERE--CAN WE ASK FOR A VOTEOT SENSE OF THE COMMITTEE. I SEE A LOT OF NODDING HEADS SO I WILL TAKE THAT AS A YES. AND WITH MY-- >> JAM DOS HAVE YOU ANY COMMENTS I SHOULD JUST ASK YOU MAYBE--I ALWAYS LIKE TO HEAR JIM'S COMMENTS? >> SO JUST SOME OF YOU KNOW THIS SOME DON'T, BUT THE--THE EARLY THERAPEUTICS CLINIC THAT I WORK IN, HAS NOW FOR YEARS ACTUALLY OPENED STUDIES FROM THE OTHER PHASE ONE INVESTIGATORS AROUND THE COUNTRY BECAUSE WE COULD FLY PATIENTS IN HERE WHO HAD NO INSURANCE WHO COULDN'T BE TREATED WITH EXPENSIVE DRUGS I THINK THAT THAT WILL ONLY EXPAND BECAUSE WE'RE NOW OFFICIALLY PART OF THE UMONE EARLY THERAPEUTICS GROUP AND THAT SAY SITUATION WHERE--FOR THOSE WHO DON'T KNOW, YOU'LL HEAR ABOUT THIS AFTERNOON, IT'S A NETWORK WHERE ALL THE TRIALS ARE OPEN AT ALL OF THE SITES AND WHERE THERE IS A NETWORK GOAL TOWARD COMPLETING A PARTICULAR DRUB DEVELOPMENT PLAN FOR A RECOMBINATION OF AGENTS AND THERE SIMPLY ARE PATIENTS FOR ONE REASON OR ANOTHER CAN'T AFFORD THE BIOPSIES THAT ARE REQUIRED AT YOUR SITE OR THAT WOULDN'T MIND FLYING AND IT'S NOT A MATTER OF OUR GETTING CREDIT FOR A GRANT, WE'RE NOT IN THE SAME GRANT POOL SO IT'S VERY HELPFUL AND SO THOSE INVESTIGATORS WHO FIGURE OUT FOR THE LAST SEVERAL YEARS HAVE MADE USE FOR THE FACT TAKEN--THEY WE COULD DO THIS QUITE REGULARLY AND I THINK IT'S BEEN VERY HELPFUL, IN THIS SOMETHING THEY THINK COULD BEING EXPANDED. >> THAT'S A GOOD POINT. >> SO, I GUESS THE BOTTOM LINE IS YOU KNOW WE'RE JUST TRYING TO TAKE PATIENTS, WE'RE NOT TRYING TO COMPETE, WE'RE TRYING TO BE SYNERGISTIC AND ALL OF US NEED TO FIGURE OUT HOW TO BETTER DO THAT. >> ANY ADDITIONAL COMMENTS OR QUESTIONS? >> THE BOUNDARIES OF WHAT CT EAC COULD HELP AND MORE IMPORTANTLY FROM AN EXTRAMURAL POINT OF VIEW, WITH KEEPING THE MONEY APART AND HOW REGULATIONS ARE HOWEE CAN COMBINE THOSE IS A WONDERFUL IDEA AND I THINK IF IT IS ALLOWED WITHIN THE CENTER REGULATION, IF WOULD BE A GREAT INITIATIVE TO BE PART OF AS CTAC. >> PAULET'S TWITCHING. >> LET ME STATE THAT INTRAMURAL PIs CAN PARTICIPATE AS COLLABORATORS ON EXTRAMURAL GRANTS. THEY JUST CAN'T RECEIVE MONEYS FROM THOSE GRANTS AND ET CETERA. SO THERE'S AN OPPORTUNITY. >> AND I SHOULD SAY, YOU KNOW BOB AND I HAVE ALWAYS BEEN ENCOURAGING AND WHAT WE--WE HAVE TO LOOK AT IT BECAUSE OUR COMMITMENT IS ALWAYS IF AN INTRAMURAL INVESTIGATOR IS PART OF A SUCCESSFUL INTRAMURALLY FUNDED GRANT. WE HAVE TO HAVE THE MONEY INTERNALLY TO SUPPORT OUR SIDE OF IT SO WE'RE JUST CARE THAFUL IN FACT WE DON'T JUST TELL SOMEONE TO DO IT AND THEN WE DON'T HAVE THE MONEY BECAUSE THAT IS A COMMITMENT ON OUR PART. >> THIS IS A BIT OPPOSITE BUT IS THAT THE INTRAMURAL PROGRAMS AND THE EXTRAMURAL COMMUNITY WANTS TO BE PART OF. SO, IF THE INTRAM INVESTIGATORS COULD BE PART OF EXTRAMURAL WORK, HERE I THINK IT'S A BIT OPPOSITE, CAN EXTRAMURAL BE PART OF INTRAMURAL AND IT'S COLLABORATIVE. >> EXTRAMURAL INVESTIGATORS CAN ACTUALLY COME INTO THE RESEARCH LABS AND PROGRAM AND PARTICIPATE IN ACTIVITIES. >> IN SOME WAYS. >> AND WE WOULD WELCOME THOSE SUCCESS AND THOSE OPPORTUNITIES WITH THEM FROM THE EXTRAMURAL COMMUNITY. >> I THINK THERE'S SO MUCH WEALTH HERE INTELLECTUALLY AND OTHERWISE THAT THE EXTRAMURAL OPPORTUNITIES WHICH ARE WONDERFUL PROJECTS FOR FUTURE DIRECTIONS WOULD BE REALLY GREAT BENEFIT. >> BUT TO GO BACK TO JIM'S QUESTION AS TO WHETHER YOU CAN FORM A DISCUSSION GROUP IN TERMS OF THE ACTIVITIES AND DISCUSSIONS THAT ARE OCCURRING NOW, THE BEST WAY TO DO THAT WOULD BE THE WORKING GROUP WHERE YOU CAN BRAINSRM AND JUST THROW OUT IDEAS AND ET CETERA. THAT WOULD BE DIFFERENT THAN FORMING A SUBCOMMITTEE OUT WHERE YOU WOULD BE EXPECTED TO COME UP WITH A SET OF RECOMMENDATIONS AND ET CETERA. >> OKAY, GREAT DISCUSSION. THANK YOU VERY MUCH LEE. SO WE'RE AT A SHORT BREAK NOW. PEOPLE CAN COME BACK ABOUT--WE'LL TRY TO GET STARTED AROUND 10:45 PLUS OR MINUS A MENUTE OR TWO. SO 10:50. ALL RIGHT, LET'S SHOOT FOR 10:50. GIVE PEOPLE TIME TO GO DOWN STAIRS AND GET COFFEE. >> OKAY, WE'RE GOING TO GO AHEAD AND GET STARTED. SO THIS NEXT SESSION REALLY INVOLVES A SERIES OF TALKS AS A MEANS OF UPDATING ON SOME ASPECTS OF THE NCTNs. WE WILL HEAR FROM DR. DOROSHOW MOONEY, ABRAMS, Mc CASKILL-STEVENS AND THEN DR. KUEBLER WILL GIVE STATS ON COMMUNITY ONCOLOGY AND CLINICAL TRIALS ACTIVITIES CONDUCTED IN THE COMMUNITY. JIM'S GOING TO LEAD OFF TALKING ABOUT AND TRY TO PUT THIS SESSION IN CONTEXT AND TALK ABOUT THE EVOLUTION OF THE LATE PHASE CLINICAL TRIALS SYSTEM. >> THANKS, JIM, SO, I GUESS AS LEE APOLOGIZED TO LOU, I HAVE LOTS OF APOLOGIES TO ALL THE INDIVIDUAL WHO IS HAVE OVER THE LAST DECADE PARTICIPATED AND I SAY THAT IT IS A DECADE, RIGHT? THAT WE'VE BEEN AT THIS. STARTING IN 2004 FOR OUR YEAR AND HALF EXPEDITION IN THE CLINICAL TRIALS WORKING GROUP, THE OPERATIONAL EFFICIENCIES WORKING GROUP. I DIDN'T PUT UP THE TRANSLATIONAL RESEARCH WORKING GROUP AND THE IOM REPORT AND AS JEFF WOULD LIKE TO SAY, IT'S BEEN EVALUATED IN GREATER DEPTH THAN THE NCI'S COOPERATIVE GROUPS BY MORE ROBUST INDIVIDUALS. AND IN ALL OF THOSE CASES, I THINK THAT THE CONCLUSION THAT WE NEED A FEDERALLY FUNDED CLINICAL TRIALS GROUP SYSTEM HAS BEEN RATIFIED. AGAIN AND AGAIN. AND THE ISSUES HAVE BEEN HOW DO WE DEVELOP A PROGRAM THAT THAT IS, FICIENT AND ADDRESSES THE KINDS OF PROBLEMS THAT ARE APPROPRIATE FOR CONTEMPORARY ONCOLOGY. SO, I THOUGHT THAT TO THE BEST WAY TO DO THIS WAS TO DO A LITTLE--WE LIKE TO CALL IT--IN DCCCD FARM CO ARCHEOLOGY, BUT BASICALLY TO GO BACK TO SOME OF THESE REPORTS AND SAY, WELL, WHAT DID WE--WHAT DID WE WRITE 10 YEARS OKAY AND DID WE HAVE ANY IDEA WHAT WE WERE WRITING IN RETROSPECT AND SO, IN FACT, IF YOU GO TO THE CTWG REPORT AT THE BEGINNING. IT OUTLINES THE RATIONAL FOR ONCE AGAIN LOOKING AT THE COOPERATIVE GROUP SYSTEM. THIS, AS YOU RECALL, THIS IS ONLY FOUR OR FIVE YEARS AFTER THE ARMITTAGE COMMITTEE HAD DONE ITS REVIEW. BUT THE FACT IS THAT THE RATIONAL FOR CHANGE WHAT WE THOUGHT OF A COUPLE OTHER SITES I COULDN'T BELIEVE THAT THESE WERE STILL TRUE AND I THINK THAT THEY ARE AND THE RATIONAL FOR CHANGE THEN AND FOR DEVELOPING THE KIND OF SYSTEM WE WANT IS IN CHANGE NOTHING CANCER BIOLOGY AND MOVING PAST CYTOTOXIC THERAPIES AND TO UTILIZE THE INFORMATION THAT WAS THEN WHERE WE HAD A MEETING OF THE CTWG WAS A FEW WEEKS AFTER THE SCIENCE AND NEW ENGLAND JOURNA IDENTIFYING THE MUTE ANT ADENO CARCINOMA IN THE LUNG WERE PUBLISH TODAY EGFR INHIBIORS, SO THERE WAS GREAT HOPE THAT IN FACT THERE WOULD BE MANY MORE SIMILAR SUCCESSES AND AS WE ALL KNOW, THAT HAS THAT HOPE HAS COME TO FRUITION. THE GOALS THAT WERE IN THE REPORT WERE TO IMPROVE OUR SYSTEM, TO IMPROVE DATABASES THAT WOULD ALLOW US TO UNDERSTAND WHAT WAS ACTUALLY GOING ON ON A--IF NOT A REALTIME BUT A VERY MUCH MORE FASTER TIMELINE. ON WHAT ACCRUAL WAS GOING ON AROUND THE COUNTRY SO THAT IF AN INDIVIDUAL AT A SMALLER INSTITUTION WANTED TO DO A TRIAL, WOULD THEY KNOW THAT THEY'VE ALREADY COMPLETED THAT TRIAL AND TOWARDS COMPLETING IT AND HOW DO WE DEVELOP INCENTIVES FOR COLLABORATING AS A NETWORK TO FIND THE APPROPRIATE PATIENTS? HOW DO WE DEVELOP A SYSTEM TO PRIORITIZE THE TRIALS WE CAN AFFORD TO DO USING THE MOST APPROPRIATE TOOLS OF MOLECULAR ONCOLOGY AND HOW DO WE DO THAT BETTER? HOW DO WE DEVELOP A STANDARDIZED I.T. INFRARE AND OTHER CLINICAL RESEARCH TOOLS THAT WILL MAKE THE SYSTEM REALLY SOMETHING THAT WILL FUNCTION AS A NETWORK. THERE WAS A LOT OF DISCUSSION AND THEN ACTUALLY SEVERAL MINIPEER REHAVE YOU PUBLICATIONS DEMONSTRATING THE LACK OF OPERATION AT EFFICIENCY IN THE SYSTEM. THAT AT THE TIME WE STARTED THE STUDIES WAS TAKING ON THE ORDER OF SEVEN OR EIGHT TRIALS TO GET THESE GOING, AND I THINK ALL OF YOU KNOW THERE HAVE BEEN DRAMATIC IMPROVEMENTS IN EFFICIENCY IN THAT REGARD AND WELL DOCUMENTED AND HOW DO WE INTEGRATE A MANAGEMENT SYSTEM AND INTRAMURALLY AND EXTRAMURALLY AND THE GOALS OF THE RESTRUCTURING AND THE FACT THATINANCE THAT'S WE'VE HAD 25 MEETINGS OF THIS COMMITTEE IS A CLEAR OUTPUT OF THAT REPORT THAT THERE WOULD BE AN EXTRAMURAL GROUP THAT WOULD BE KEEPING OUR FEET TO THE FIRE, MAKING SURE WE WERE IMPLEMENTING THE GOALS FOR RESTRUCTURE BEING. SO FOR TODAY, WE'RE GOING TO HAVE TALKS BY MEG MOONEY, ABOUT THE NCTN ABOUT SETTING GOALS GOING FORWARD FOR THE NCTN BY JEFF ABRAMS, ABOUT THE REDO OF THE CCOP PROGRAM INTO NCORP. THERE'S VERY SIGNIFICANT AND HIGHLY RELATED REDO OF OUR THERAPEUTICS PROGRAM THAT PERCY IVY WILL TALK ABOUT AND JEFF SCHAPIRO WILL TALK ABOUT IN A DIFFERENT WAY THAT WE GO ABOUT DOING EARLY PHASE OF NCI EARLY PHASE EVICTIONS SO I WOULD LIKE TO LEAVE YOU WITH THIS TO THINK ABOUT WHAT WE WANTED TO DO AND WHAT WE ACTUALLY SRO DONE, HOW WELL THAT'S WORKING OVER THE COMMUNITIES BUT PEE DO HAVE INTEGRATED NETWORK THAT'S CAPABLE OF SUPPORTING STUDIES THAT ARE BASED ON THE PRINCIPLE PRECISION MEDICINE AND I THINK THE FACT THAT THE ALCHEMT TRIAL LUNG MATCH, ET CETERA ALL THOSE ARE UP, RUNNING, SOON WILL BE UP AND RUNNING. AND BASICALLY EMPHASIZE THE FACT THAT WE'RE ABLE ON TO DO THAT BECAUSE WE HAVE AN INTEGRATED WAY TO GO ABOUT DOING THAT, DOING THOSE KINDS OF STUDIES. OUR TOOLS, OUR NATIONAL TOOLS WHETHER THEY'RE A CENTRAL IRB THAT WORKS ACROSS ALL OF OUR TRIALS INTEGRATED I.T. SYSTEM, THOSE ARE UP AND RUNNING. AND WE HAVE CUT THE TIME TO OPEN A PHASE THREE TRIAL DOWN TO ABOUT A YEAR. BETTER THAN 50% IMPROVEMENT. IMPROVEMENT IN EARLY PHASE STUDY SYSTEM AROUND 30-35% IS BETTER. WE ARE CONTINUING TO IMPROVE. OUR GOAL IS TO AT LEAST GET TO PHARMACEUTICAL INDUSTRY NORMS IN THOSE AREAS AND I THINK THERE'S A GOOD REASON TO BELIEVE THAT WE CAN DO THAT AND IN FACT. ALL OF THOSE ACTIVITIES HAVE ACCOMPLISHED, NOT ONLY THE TRIALS THAT YOU TALK ABOUT BUT OTHER TRIALS THAT WILL UTILIZE THE REMARKABLE TOOLS THAT WILL ENVISION AND AND CLINICAL PRACTICE IN ONCOLOGY AND I WILL INTRODUCE DR. MOONEY. SO JUST IN TERMS OF--BECAUSE WE HAVE A LOT OF PRESENTATIONS IN IN SESSION, I WOULD LIKE TO SUGGEST THAT WE TAKE QUESTIONS FOR JIM, MEG, AND JEFF AFTER MEG AND JEFF'S PRESENTATION AND THEN WE'LL TAKE QUESTIONS REGARDING THE NCORP AND THE QUESTIONS THAT AFTER EACH OF THOSE RESENTATIONS, I THINK IT WILL ORGANIZE OUR THINKING AND HOPEFULLY BE ABLE TO PROVIDE SOME SALIENT COMMENTS BACK IF WE ORGANIZE IT THAT WAY. >> OKAY, WELL, THANK YOU. I'M HAPPY TO BE HERE THIS MORNING TO PRESENT AN OVERVIEW OF THE NEW NCI NATIONAL CLINICAL TRIALS NETWORK ALTHOUGH IT HAS BEEN WORKING MARCH FIRST THIS YEAR. SO THIS IS ONLY A LITTLE UNDER FOUR YEARS PROGRESS SO IT'S PROGRESS IN THAT REGARD BUT WE LAID OUT AN AGGRESSIVE PERIOD IN WHICH TO TRANSFORM THE FORMER COOPERATIVE GROUP SYSTEM INTO THE NEW NCTN. WE HAD ABOUT A YEAR AND HALF PRE-PERIOD WHERE WE GOT WIDE SPREAD STAKEHOLDER INPUT ON HOW TO REDESIGN THE TRIAL IN THE LATE PHASE NETWORK AS WELL AS BUILDING ON THE REPORED FROM THE INSTITUTE OF MEDICINE, BUT AFTER THAT WE WENT TO THE NCI BOARD OF SCIENTIFIC ADVISOR IN NOVEMBER OF 2011 AND GOT APPROVAL FOR A NEW CONCEPT TO TO REVAMP THE SYSTEM AND FROM THEN TO MARCH OF THIS YEAR WE LAID OUT A SERIES OF TIME PERIODS TO GIVE A BIG SYSTEM AND TO GIVE ALL THE GRANTEES AND THE EXTRAMURAL COMMUNITY ENOUGH TIME TO AND TO TRANSFORM INTO THE NEW NOTE WORK AND THAT WAS ABOUT AN 18 MONTH PERIOD BUT WE WERE ABLE TO SUCCESSFULLY RUN THAT DESPITE THE GOVERNMENT SHUT DOWN AND OTHER ISSUES AND WE WERE ABLE TO LAUNCH THE NEW NETWORK ON MARCH FIRST. THE VISION FOR THIS WAS LAID OUT IN THE PRIOR YEARS OF PLANNING WHERE WE WANTED TO MAKE SURE THAT WHATEVER--HOWEVER WE DECIDE OFFICE OF DIVERSITY WHICH TRIALS WERE THE MOST IMPORTANT TO GO FORWARD, THAT WE MADE SURE THAT WE LAUNCH THOSE TRIALS RAPIDLY AND COMPLETED ACCRUAL PERDEFINED GUIDELINES AND MADE SURE WE DID THIS AS AN INTEGRATED NATIONAL NETWORK. WE WANTED TO ALSO MAKE SURE WE HAD HARMONIZED USER FRIENDLY PROCESSES WHICH WERE THE SAME FOR EVERYONE WHO PARTICIPATE INDEED THE NETWORK, NO MATTER WHICH NETWORK LED THE TRIAL. WE WANTED ALSO TO MAKE SURE THAT WE HAD A COMMON INFRASTRUCTURE TO REALLY PERFORM WHAT WE FELT WERE REALLY THE NECESSARY TRIALS THAT WE WOULD NEED TO DO IN THE FUTURE. PARTICULARLY TRIALS THAT WOULD INVOLVE LARGE SCALE TESTING OF INCREASINGLY SMALLER SUBSETS OF MOLECULARLY DEFINED TUMORS AND I WILL GIVE A FEW EXAMPLES OF THOSE TRIALS TWO OF WHICH ARE ALREADY OPEN AND LAST BUT NOT LEAST WE WANT TO FOCUS ON RESEARCH QUESTIONS THAT ARE NOT ALWAYS WELL SUPPORT INDEED A COMMERCIAL ENVIRONMENT. SO AS YOU--MANY OF YOU KNOW THE FORMER COOPERATIVE GROUP SYSTEM WAS BASED ON 10 DECENTRALIZED U.S. GROUPS. WE HAD OVER THE YEARS TRIED TO PUT COMMON PROCEDURE INTO'S PLACE AND WE'RE SUCCESSFUL WITH THAT UP TO A DEGREE. BUT WE STILL HAD 10 GROUPS THAT FUNCTION SOMEWHAT INDEPENDENTLY CERTAIN THREE THEIR GRANT STRUCTURE WAS INDEPENDENT AND THE TIMING OF THE REVIEW WAS INDEPENDENT OF ONE ANOTHER. WE ALSO DUPLICATED MANY ADMINISTRATIVE AND REGULATORY FUNCTIONS WITHIN EACH OF THE 10 GROUPS. AS WELL. SO WE REALLY COULDN'T MOVE FORWARD IN AN INTEGRATED NETWORK UNLESS WE TOTAL REVAMP THE SYSTEM. AND THAT WAS THE PURPOSE OF THE NEW THIS, CTN STRUCTURE. WE FELT THIS WAS THE STRUCTURE WE NEEDED TO OPTIMIZE SCIENTIFIC OPPORTUNITIES IN THE FUTURE. WE HAVE NOW TRANSITIONED TO FIVE U.S. GROUPS. WE ALSO HAVE ONE CANDNANOG COLLABORATING NETWORK GROUP THAT,'S THE NCIC CTFG OF CANADA. WE ALSO HAD A PROGRAM IN THE OLD COOPERATIVE GROUP WHERE HIGH ACCRUING INSTITUTIONS AND THOSE THAT PROVIDED US SIGNIFICANT SCIENTIFIC LEADERSHIP WITHIN THE GROUP WERE TIED TO INDIVIDUAL GRANTS BUT THEY WERE TIED TO GRANTS WITHIN PARTICULAR COOPERATIVE GROUP AND IT WASN'T SPREAD OUT ALL THE COOPERATIVE GROUPS SO AS WE MOVED FORWARD, WE WANTED TO MAINTAIN THAT BUT WE ALSO WANTED TO EXPAND IT TO MAKE SURE THAT WE GAVE INDIVIDUALS GRANTS TO THOSE INSTITUTIONS THAT PROVIDED SIGNIFICANT SCIENTIFIC LEADERSHIP AND ACCRUAL FOR WHAT THEY DID ACROSS THE NETWORK. NOT JUST WITH ANY PARAR NETWORK GROUP. WE ALSO INSTITUTED TRANSLATIONAL SCIENCE AWARDS SO MAKE SURE WE HAD BETTER FUNDING AND COLLABORATION WITH INTEGRATION WITH TRANSLATIONAL SCIENTISTS FOR WHAT THEY COULD BRING TO THESE LARGE SCALE CLINICAL TRIALS AND WE ALSO INTEGRATED A NEW CENTRALIZATION OF RADIO THERAPY AND IMAGING QUALITY ASSURANCE FOR THE CLINICAL TRIALS SO THAT WOULD BE A CORE INTEGRATED SERVICE THAT WOULD SUPPORT THE ENTIRE NETWORK. WE ALSO APPLIED INTEGRATION AND NCORP, WE WILL PEEK ABOUT LATER THIS MORNING BUT WE WANT TO MAKE SURE THAT THE INFLAY STRUCTURE WOULD SERVE BOTH PROGRAMS AND WE DOPE AS MUCH AS WE CAN DOJ THAT. SO ALL THE CENTRALIZED PROCEDURES LIKE THE CENTRAL IRB, AND THE MINIARRAY AND ALL THE PROCESSES ARE INTEGRATED BETWEEN THE TWO PROGRAMS AND FOR THE FIRST TIME WE HAVE AN INTEGRATED ROSTER OF SCIENCE BETWEEN THE TWO PROGRAMS, SO WE NOW KNOW EXACTLY WHOSE ACCRUING IN REALTIME BASIS TO WHICH TRIALS AND FROM WHICH INSTITUTIONS AND UNDER WHICH PROGRAM. YOU CAN SEE THAT THE FOCUS IN TERMS OF OUR RESEARCH IS A LITTLE BIT DIFFERENT, OBVIOUSLY AND THE NCTN, WE FOCUS ON LATE PHASE TREATMENT TRIALS AND ADVANCED IMAGING TRIALS AND OF COURSE PRIMARY FOCUS IS IN PRIMARY CONTROL TRIALS AS WELL AS COMARRAATIVE EFFECTIVENESS RESEARCH. HERE ARE THE MAJOR COMPONENTS, I WON'T GO OVER THEM AGAIN BUT WE DID ELICIT SIX RFAs SO THAT WE COULD AT THE SAME TIME REVIEW AND MAKE SCIENTIFIC AND FUNDING DECISIONS ACROSS THE SAME NETWORK FOR ALL THE SIX INTEGRATED COMPONENTS. WE'VE ALSO LISTED AND IT IN YOUR PACKAGE THE AWARDEES UNDER EACH OF THE SIX RFAs. HERE YOU SEE TWO RFAs, THE OPERATIONS AND THE STATISTICAL DATA MANAGEMENT CENTERS FOR EACH OF THE FIVE U.S. GROUPS AS WELL AS ONE FEEDIATRIC GROUP AND THE CANDNANOG CLINICAL TRIALS GROUP WHICH IS OUR COLLABORATING PARTNER IN CANADA. MANY IN NOT MOST OF THESE AWARDS ARE ALSO MULTIPLE PI AWARDS. WE WERE ABLE TO DO THAT FOR THE FIRST TIME WE DIDN'T HAVE THAT UNDER THE PREVIOUS COOPERATIVE GROUP PROGRAM BUT NOW EACH OF THE GRANTEES OR AWARDEES ARE ABLE TO APPROPRIATELY RECOGNIZE THE REALLY TEAM SCIENCE THAT UNDERLINES ALL OF THESE NETWORK GROUPS. WE WERE ALSO ABLE TO PARPARTICIPATE IN A TRIAL IN THE SLIDE BY ALPHABETICAL ORDER BY NAME OF INSTITUTION AND THE ORDER DOESN'T MEAN ANYTHING IN PARTICULAR IN THIS REGARD, WE WOULD HAVE LIKED TO AWARD MORE THAN 30 BUT GIVEN THE BUDGET SITUATION, WE FELT COMFORTABLE THAT WE COULD AT LEAST FULLY SUPPORT THESE 30 PRINCIPLE LEAD ACADEMIC GROUPS NEAR THE FETE WORKS. SO THE SECOND PAGE IS HERE WITH THE ADDITIONAL END OF THE LIST OF THE 30. EXCUSE ME THEN WHEN WE LOOK OVER THE GEOGRAPHIC DISTRIBUTION, WE FELT WE HAD GOOD GEOGRAPHIC DISTRIBUTION OF THE SITE THAT SUPPORTS THE NCTN NETWORK IN ADDITION WE HAVE THE NCORP PROGRAM THAT WE HAVE LARGE OF THE COMMUNITY CENTERS THAT PARTICIPATE IN THE NCTN, AND THE NCORP PROGRAM ITS. THESE COME FROM A VARIETY OF CTNGROUPS ACROSS THE COUNTRY AS WELL. SO A RESEARCH AGENDA GOING FORWARD: OBVIOUSLY WE'RE A LATE PHASE CLINICAL TRIAL SYSTEM, WE DO MAINLY LARGE PHASE TWO TRIALS AND DEFINITIVE LARGE PHASE THREE PRACTICE CHANGING TREATMENT AND ADVANCE IMAGING TRIALS. WE ARE LOOKING TO TRY TO MAKE SURE THAT THE NEW INTEGRATED NETWORK IS ABLE TO DESIGN AND DEVELOP AND CONDUCT TRIALS WITH NOVEL AND MOLECULARLY TARGETED AGENTS, PARTICULARLY WHEN WE THINK--WHEN THEY COME FROM DIFFERENT SPONSORS BECAUSE THAT'S A UNIQUE ROLE THAT A PUBLICLY FUNDED SYSTEM CAN OFTEN PLAY. WE ALSO WANT TO MAKE SURE THAT WE INTEGRATE THESE NEW AGENTS AND IMAGING APPROACHES AND AS A STANDARD OF CARE, ANOTHER AREA THAT OFTEN ISN'T SUPPORTED WELL WITHIN AN ENVIRONMENT AND IN ADDITION, THEY HAVE MULTIREGIMENS THAT INCLUDE THERAPY AND WE HAVE A FOCUS ON CANCER AND PEDIATRIC CANCER IN GENERAL AND A RARE CANCER BUT WE'RE LOOKING TO DO MORE TO DEVELOP TRIAL ASKS RARE CANCERS IN THE ADULT SEER PATIENT POPULATION AS WELL AS UNCOMMON PRESENTATIONS OF MORE COMMON CANCERS WHERE WE THINK WE HAVE A PARTICULAR APPROACH THAT MIGHT BENEFIT THOSE PATIENT POPULATIONS. WE ALSO DO LOOK AT DIFFERENT TREATMENT AND IMAGING APPROACHES THAT ARE ALREADY APPROVED FOR CLINICAL CARE. WHEN THAT MAKES SENSE AS WELL. SOME OF THAT IS DONE IN COMPARATIVE EFFECTIVENESS BY NCORPS AND IT'S DONE IN TREATMENT TRIALS AS WELL. SO WE DID WANT TO HIGHLIGHT TRIALS TO SPEAK TO AND NETWORK APPROACH IN PARTICULAR, THE EXTRAMURAL COMMUNITY AS WELL AS NCI HAS BEEN TRYING TO DEVELOP A NATIONAL STRATEGY FOR PRECISION MEDICINE TRIALS AND I WILL SHOW YOU A COUPLE OF THOSE THAT HAVE ALREADY BEEN OPENED WITHIN THE NCTN. WE'RE TRYING TO HELP ADVANCE OBVIOUSLY MOLECUAR PROFILING FROM RESEARCH USE INTO THE CLINIC. WE ARE LOOKING AT DOING GENO TYPE TO PHENOTYPE WHERE WE DEVELOP A PORTFOLIO OF TRIALS ACROSS THE SPECTRUM TO ADVANCE DISEASE TO SCREEN FOR THE FEATURES THAT WE THINK MAY PREDICT A RESPONSE TO A PARTICULAR DRUG OR COMBINATION THERAPY AND MULTIMODALITY THERAPY AND WE WANT TO EXPAND THE RESEARCH SO THAT WE CAN HOPEFULLY ANALYZE TUMOR SPECIMENS THAT RELAPSE AND DEFINE MECHANISMS OF RESISTANCE. AND ALSO TO DEVELOP THE DATABASES TO CLINCH THE CLINICAL OUTCOMES WITH THE MOLECULAR TUMOR CHARACTER FOR FIXED CONTINUED RESEARCH. SO THREE OF THESE ARE DOING THE TRIALS ONE IS ALCHEMIST, ONE IS NCI MATCH AND I WILL GIVE YOU A FLAVOR OF THOSED ST'S RIGHT NOW. WE HOPE THAT NCI MATCH IS OPEN AND PLAN FOR ACTIVATION BY THE END OF THE FIRST QUARTER OF 2015. WE ALSO HAVE A STUDY, BUT IT IS AN NCI INITIATIVE THAT YOU MAY HAVE HEARD OF TO LOOK AT PHENOTYPE TO GENOTYPE ISSUE WHERE WE'RE LOOKING FOR FOLLICULAR MUTATIONS OR CHANGES IN GENE EXPRESSION THAT MIGHT EXPLAIN WHY PATIENTS RESPONDED TO A TREATMENT THAT OBVIOUSLY DIDN'T WORK FOR OTHERS. THAT'S CALLED THE EXCEPTIONAL RESPONSES INITIATIVE. THAT ALSO IS HOPE IS IT'S AVAILABLE THOUGH NOT JUST FOR PEOPLE WHO BELONG TO THE NCTN, BUT THE CANCER CENTERS, PHARMA TO EVERYONE, WHAT WE'RE TRYING TO DO IS HAVE THE EXTRAMURAL COMMUNITY SENDING CASES WHERE THEY THINK SOMEONE HAD AN EXCEPTIONAL RESPONSE WHERE TUMOR MAY BE AVAILABLE SO THAT WE CAN LOOK BACK AND SEE IF THERE'S ANY REASON WE THINK THAT MIGHT HAVE BENEFITED THAT PARTICULAR PATIENT WHEN IT DIDN'T BENEFIT THE THE WHOLE PATIENT POPULATION. SO TO GIVE YOU A FLAVOR OF THE FEW OF THE MOLECULAR AND PRECISION MEDICINE TRIALS WE'VE ALREADY LAUNCHED. I WILL TALK TO YOU FIRST ABOUT THE ALCHEMIST TRIAL. THIS IS A TRIAL IN EARLY STAGE LUNG CANCER WHICH WILL EVALUATE MOLEC LARRY TARGETED THERAPY AND SMALL CELL LUNG CANCER AND SQUAMOUS CELL LUNG CANCER AND WE DON'T KNOW WHETHER IT'S GOING TO HELP PATIENTS IN AN ADJUVANT CLINICAL SETTING AND THAT'S WHAT THIS PARTICULAR PROJECT AND SERIES OF TRIALS IS SET UP TO DO. ALCHEMIST IS DESIGNED SO WE SEE PREOPERATIVELY OR POST OPERATIVELY. PATIENT WHO IS HAVE UNDERGONE RESURGICAL RESECTION WITH THE APPROPRIATE HISTOLOGIES AND WE LOOK FOR WHETHER THEY HAVE THE MOLECULAROTERATION THAT MIGHT SUGGEST THAT THEY WOULD BENEFIT FROM HERLOTNIB THERAPY OR OTHER THERAPY AND WE ARE LOOKING FOR ACTIVATING PATIENTS IN THE TREATMENT TRIAL FOR THOSE WHO HAVE TUMORS WITH WITH THE OUTFUSION PROTEIN. SO THEY WILL GET--ONCE THE PATIENTS ARE IDENTIFIED THEY WILL BE REFERRED TO THE TREATMENT TRIALS AND ENTER INTO THOSE RANDOMIZED TREATMENT TRIALS AFTER COMPLETION OF ADJUVANT THERAPY TO SEE WHETHER THEY BENEFIT. BUT THIS IS ALSO SET UP AND HERE'S THE SCHEMA SO THAT WE COLLECT FOR ALL THE PATIENTS THAT WE SCREEN THAT WE DON'T--WILL GO ON TO STANDARD OF CARE BECAUSE THEY DON'T HAVE THE MODEL CITIZEN LEAKULAR MUTATION THAT WE'RE LOOKING FOR FOR THE TWO TREATMENT TRIALS BECAUSE WE THINK ONLY THOSE PATIENTS WILL POTENTIALLY BENEFIT WE'RE ALSO COLLECTING EPIDEMIOLOGIC INFORMATION AS WELL AS ADVANCED GENOMIC ANALYSIS THAT'S GOING TO BE DONE BY THE NCI CENTER FOR CANCER DENATIONAL LIBRARY OF MEDICINICS IN COLLABORATION WITH THE EXTRAMURAL INVESTIGATORS FOR ALL THOSE SCREENED PATIENTS SO HOPEFULLY WE WILL BE ABLE TO MAKE ALL THAT INFORMATION AS WELL AS FIVE YEAR OUTCOME INFORMATION AVAILABLE IN A LARGE PUBLIC DATABASE, FOR CONTINUED RESEARCH. SO THAT ALL PATIENTS EVEN THOSE THAT ARE SCREENED AND DON'T GO ON TO A TREATMENT TRIAL WILL GO ON TO CONTRIBUTE TO THE RESEARCH EFFORT. IN ADDITION THAT IS SET UP SOPHISTICATED THAT THERAPIES THE PATIENTS IN THE ADJUVANT SETTING WE COULD ADD THEM IN A MODULAR WAY TO THE ENTIRE PRODUCT AND WE COULD IBT--INTEGRATE CORPORATE THOSE PATIENTS AS WELL AND THEY COULD BE REFERRED TO A TREATMENT TRIAL AS WELL. THE OTHER IS LUNG MAP, IT'S FOR THE MASTER PROTOCOL IS A UNIQUE PUBLIC-PRIVATE PARTNERSHIP WITH THE FNIH, NATIONAL INSTITUTE AND FDA WHERE A MASTER PROTOCOL WAS DEVELOPED FOR PATIENTS WITH ADVANCED SQUAMOUS CELL CARCINOMA THIS IS A BIOMARKER FOR SECOND LINE TREATMENT OF PATIENTS WITH SQUAMOUS CELL LUNG CANCER. IT'S A MULTIARMED ANDROGEN ORDER OF MICRONSIZED CONTROL-THREE CLINICAL TRIAL IN WHICH OF THE INDIVIDUAL ARMS ARE SET UP AS INDEPENDENT PHASE TWO AND THREE TRIALS. PATIENTS ARE SCREENED FOR PARTICULAR MOLECULAR ALTERATIONS, THEY'VE ASSIGNED TO THE APPROPRIATE TREATMENT APPROACH AND EACH OF THE ARMS AS POWERED EVENT YULELY TO GO TO A PHASE THREE REGISTRATION TRIAL, SHOULD THEY PASS A PHASE TWO BARRIER. THIS TRIAL IS LED BY FLOG BUT IT'S DESIGNED WITH THE PARTICIPATION OF ALL THE GROUPS IN THE NCTN AND THEY'RE ALL PARTICIPATING AS WELL AS ALL THE SITES OBVIOUSLY IN THE NCOR AND NCTN. SO HERE'S JUST A BRIEF SCHEMA, PATIENTS COME IN, THEY HAVE CLINICAL CLE O LAB PROFILING OF THE MOLECULAR TUMORS THAT WE THINK MIGHT BE AMENABLE FOR A PARTICULAR THERAPIES THAT WE INCLUDE IN THE TRIAL, PATIENTS ARE THEN ASSIGNED TO THE PARTICULAR TRIAL. IF THEY HAVE THOSE MOLECULAR ALTERATIONS WHICH AS I SAID ARE ALL DESIGN AS INDEPENDENT PHASE TWO AND THREE TREATMENT TRIALS. THERE'S ALSO AN UNMATCHED ARM SO AT THIS POINT EVERYONE WHO GOES ON IF THEY DON'T HAVE A ALTERATION, CAN GO ON TO THE NONMATCH ARM WHICH IS EVALUATING IMMUNOTHERAPY. THE NEXT TRIAL WILL BE OPEN TO THE ENTIRE NCTN AND NCORP NETWORK, IT IS AN UMBRELLA PROTOCOL THAT'S A SINGLE SEEKING, SERIES OF SINGLE ARM PHASE TWO TRIALS ACROSS VARIOUS CYSTOLOGYS SO IN THIS CASE WHAT WE'RE DOING IS IDENTIFYING A VARIETY OF HISTOLOGIES, PATIENTS WITH TUMORS WITH THE MODEL CITIZEN LEAKULAR ALTERATIONS, WHERE WE THINK A PARTICULARLY TARGETED AGENT MAY LEAD TO A POTENTIAL RESPONSE FOR THEM. THIS IS OBVIOUSLY FOR PATIENT WHO IS HAVE ALREADY UNDERGONE STANDARD OF CARE IN THE ADVANCE DISEASE SETTING. BUT THE DISEASE PROGRESSED ASK WE WILL DO TUMOR BIOPSIES TO HOPEFULLY ELIMINATE RESISTANCE MECHANISMS WITHIN EACH OF THESE INDIVIDUAL ARMS, WE HOPE TO HAVE ANYWHERE FROM 10-20 INDIVIDUAL ARMS OR DRUGS THAT WOULD BE AVAILABLE ACROSS A SPECTRUM OF MOLECULAR MUTATION FOR PATIENT WHO IS CAN BE ENTERED INTO THE TRIAL. THIS IS ALSO UNIQUE, THAT THERE WILL BE ONE IND FOR THE ENTIRE NETWORK, EVEN THOUGH--EXCUSE ME ENTIRE PROTOCOL EVEN THOUGH IT INVOLVES A SERIES OF DIFFERENT DRUGS AS WELL AS CORPORATE SPONSORS. IT'S INITIALLY FOCUSED ON SINGLE AGENTS, EITHER COMMERCIAL OR EXPERIMENTAL IN MOST CASES MANY OF THEM WILL BE EXPERIMENTAL AND IT WILL BE UNDER THE CENTRAL IRB SO IT'S A VERY LARGE SIGNAL SEEKING TRIAL THAT WILL BE OPEN TO THE ENTIRE NETWORK ACROSS VARIOUS CYSTOLOGYS. WE'RE ALSO PLANNING TO EXPAND ON THIS AREA, WITHIN THE NCTN, THERE IS A PEDIATRIC MARCH THAT THE EQUIVALENT SORT OF TO WHAT'S BEING DONE FOR NCI AND THE MATCH FOR THE ADULT PATIENTS FOR THE PEDIATRIC PATIENT POPULATION IN LABERATION WITH LEE HELMAN AND HIS GROUP IN THE INTRAMURAL PROGRAM THAT THE CHILDREN'S ONCOLOGY GROUP WILL BE CONDUCTING. WE'RE ALSO LOOKING AT AN ADDITIONAL MASTER PROTOCOL. EVALUATING SECOND GENERATION OUT INHIBITORS COMPARED TO THE CRIZOTNIB, FOR THOSE IN ADVANCED LUNG CANCER. SO WE HOPE AS WE GO FORWARD THAT THIS NETWORK WILL HELP US ADDRESS THESE TYPES OF QUESTIONS. AND HELP US ALSO ADD ON TO THE GENERAL RESEARCH ENVIRONMENT IN TRYING TO UNDERSTAND WHY TREATMENTS WORK AND WHY RESISTANCE DEVELOPS. MORE OFTEN TRYING TO DEVELOP A SERIES OF OTHER APPROACHES BY WHICH WE CAN WORK AS A NETWORK. WE DO HAVE A MEETING PLANNED FOR DECEMBER 4th AND 5th WHERE WE WILL GET REPRESENTATIVES FROM EACH OF THE 30 LEAD ACADEMIC PARTICIPATING SITES PLUS THE FIVE U.S. NCTNGROUPS AS WELL AS CANADIAN PARTNER, PATIENT ADVOCATES AND REPRESENTATIVES FROM THE NCI BUT WE WANT TO LOOK AT ACCRUAL CHALLENGES THAT PEOPLE ARE FACING WITH THESE NEW DRIVEN TRIALS AND TRY TO UNDERSTAND HOW WE CAN MAXIMIZE THE NETWORK TO MAXIMIZE THE ACCRUAL TO THESE TRIALS AND WHAT WORKS AND DOESN'T WORK, ET CETERA. SO THAT GIVES YOU AT LEAST THE FLAVOR OF WHERE WE'RE GOING WITH THE NCTN AND I WILL BE HAPPY AT THE END OF ALL THE TALKS TO ANSWER ADDITIONAL QUESTIONS. THANK YOU. >> THANK YOU MEG. WE WILL NOW HAVE JEFF WHO'S GOING TO TALK MORE ABOUT SOME OF THE IDEAS AND STATUS OF WHERE--WHERE WE STAND IN TERMS OF DOING PERIODIC REVIEW OF PORTFOLIOS OF FOLKS FROM STEERING COMMITTEES, BUT ALSO HAD PRIOR DISCUSSIONCROSS PORTFOLIO REVIEWS AND I THINK JEFF'S GOING TO KIND OF UPDATE WHERE WE ARE WITH THAT PROCESS. THIS IS GOING TO COME BACK TO US AGAIN, I THINK MORE FORMALLY IN THE MARCH MEETING. HERE I THINK WE'RE KIND OF LOOKING AT WHERE WE STAND WITH THIS PROCESS THINKING ABOUT ARE THEY ARE ON THIS RIGHT TRACK ASK I'LL LET JEFF TAKE IT FROM HERE. >> THANK YOU JIM. GOOD MORNING. SO AS MANY OF YOU KNOW THE WAY WE PRIORITIZE THE TRIALS THAT MEG JUST DESCRIBED TO YOU IS THROUGH THE STEERING COMMITTEE PROCESS AND BOB AND GEORGE SLEDGE LED A VERY THOROUGH NCTN WORKING GROUP ANALYSIS OF THE STEERING COMMITTEES AND HOW THEY WERE DOING AND THEY CAME UP WITH SEVERAL RECOMMENDATIONS WHICH HAVE OR WERE DISCUSSED I BELIEVE AT THE LAST CTAC MEETING AND WE WANT TO SHOW YOU THIS MORNING AS JIM SAID THE EVOLUTION OF THE THINKING OF HOW TO GO FORWARD TO HAVE A PROCESS THAT WILL CONTINUALLY EVALUATE HOW OUR DISEASE SPECIFIC STEERING COMMITTEES ARE FUNKING. SO ONE OF THE MAJOR RECOMMENDATIONS FOR THE WHOLE REVIEW IS THAT WE NEED TO SET STRATEGIC PRIORITIES FOR THE NCTN TRIALS IN THE GIVEN DISEASES IN THE ADZ VANCE AND THE CONCEPT FOR INNOVATION WOULDN'T BE CONSIDERED AND THIS MAY BE INFORMATION IF YOU'RE MOVING OUT OF THE COMMITTEE WHAT THEIR STATUS IS HIGH PRIORITY. IT IS TRUE THAT THE NCTN GROUPS ARE RESPONSIBLE FOR CONCEPT DEVELOPMENT AND RECOMMENDATION FROM THE GROUP AND FINALLY THE STEERING COMMITTEE'S JOB IS TO EVALUATE ALL THE CONCEPTS RIGOROUSLY FOR THEIR SCIENTIFIC AND CLINICAL QUALITY. IRRESPECTIVE OF WHETHER THEY ALINE OR NOT WITH A STRATEGIC PRIORITY. IN OTHER WORD FIST THEY ALINE WITH THE PRIORITY, IT HAS TO BE A SOLID CLINICAL TRIAL THAT MEETS ALL THE REQUIREMENTS TO GO FORWARD IN THE NCTN. NOW HOW WE'RE GOING TO SET UP THESE TRANSLATIONAL RESEARCH TEGGIC PRIORITIES, THIS WILL BE A JOINT DISCUSSION BETWEEN THE NCTN GROUPS AND THE STEERING COMMITTEE MEMBERS. THE GROUPS WILL PROPOSE STRATEGIC PRIORITIES FOR DISCUSSION. HOPEFULLY THEY WILL COLLABORATE AMONGST THE DIFFERENT GROUP LEADERS AND THEIR DIFFERENT DISEASE COMMITTEES, AND WE WILL ALSO SOLICIT OUTSIDE INPUT. IT WILL BE IMPORTANT FOR THE--FOR THE STEERING COMMITTEE TO ASSESS WHETHER ALL THE GAPS IN THE LANDSCAPE IN THAT DISEASE HAVE BEEN ADEQUATELY COVERED AND WE DON'T WANT A LAUNDRY LIST OF PRIORITIES, WE ARE LOOKING FOR A FEW KEY PRYERITYS. SO THAT WE CAN REALLY FOCUS INVESTIGATORS ATTENTION ON TRIALS THAT ARE LIKELY TO SUCCEED ON CONCEPTS THAT ARE LIKELY TO BE APPROVED IF THEY ANSWER THE QUESTION WELL. AND THESE PRIORITIES WILL HAVE TO BE REVIEWED AS LEAST ANNUALLY AND REVISED AS NECESSARY. NOW, WE DO EXPECT THE STRATEGIC PRIORITY SETTING TO BE A VERY COLLABORATIVE PROCESS AND AS I SAID IT WILL INVOLVE THE GROUPS AS WELL AS STEERING COMMITTEE MEMBERS AND POSSIBLY OUTSIDE EXPERTS. THE PROCESS IS FLEXIBLE. WE'RE NOT STATING THAT IT HAS TO BE IMPLEMENTED IN A SPECIFIC WAY. IT MAY BE IMPORTANT IN DIFFERENT DISEASES TO TAKE SLIGHTLY DIFFERENT APPROACHES TO THIS. NCI IS GOING TO PROVIDE THE COMMITTEE'S ADMINISTRATIVE SUPPORT AND THE PROCESS WILL PROBABLY BE CONDUCTED OVER A CONFERENCE CALLS POSSIBLY AND IN-PERSON MEETINGS. BUT WE DO OPEN THAT ALL THE COMMITTEES WILL HAVE STRATEGIC PRIORITIES SET AND AVAILABLE ON THE WEB SITE BY JUNE OF 15th, 2015. AND THEN AGAIN THEY WOULD HAVE BE REVIEWED ANNUALLY TO KEEP THEM UPDATED. NOW THE SECOND PART OF THIS WHICH WE'RE REALLY COMING TO YOU TODAY TO HEAR YOUR COMMENTS ON BECAUSE IT'S VERY EARLY DAYS AND DISCUSSING HOW BEST TO DO THIS BUT IT REALLY IS HOW TO REPLACE THE PROCESS THAT WE WENT THROUGH WITH THE NCTN WORKING GROUP AND ASSESSING THE STEERING COMMITTEES AND HOW TO DO THAT IN A MORE SYSTEMATIC ROUTINE WAY THAT WON'T REQUIRE THE ENORMOUS EFFORT THAT THE EXTRAMURAL COMMUNITY PUT IN DURING THAT INITIAL EVALUATION AND WE HOPE WE LEARNED SOME THINGS FROM THAT EVALUATION THAT WILL FACILITATE THIS. SO WE DO THINK IT'S IMPORTANT TO HAVE FEET FEEDBACK TO THE STEERING COMMITTEES ON HOW THEY'RE DOING AND MAKING SURE IF WE GO TO THE TROUBLE OF SETTING UP STRATEGIC PRIORITIES THAT THEY'RE ACTUALLY--THE TRIALS ARE ACTUALLY ADDRESSING THEM PROPERTILY. BUT WE FELT THE STEERING COMMITTEES COULD START OFF BY DOING THEIR OWN SELF-ASSESSMENT. THEY MIGHT OWING MENTORSHIP SKILL INDIVIDUAL SELF-ASSESSMENT WITH ADDITIONAL GROUP OR NCORP RESEARCH BASE EXPERTS BUT WE FELT BY AND LARGE THEY'RE IN THE POLINGS POSITION AFTER A PERIOD OF TIME TO ASSESS HOW HAY FEEL THEY'VE BEEN DOING WITH THE PRIORITIES THEY'VE SET. NONETHELESS WE KNOW FROM OUR LAST EFFORT OF THIS IS THAT YOU NEED A BODY, ANOTHER GROUP TO LOOK ACROSS THESE. YOU CAN'T EXPECT THE DISEASE SPECIFIC STEERING COMMITTEES TO HANDLE AND BE ABLE TO HAVE THAT FEW ACROSS ALL DISEASES AND SO, WE HOPE TO HAVE A CTAC WORKING GROUP THAT WOULD INCLUDE THE NCTN GROUP CHAIR THAT WOULD LOOK AT THE ACROSS DISEASE PORTFOLIO TO SEE OVERALL ARE WE STRATEGICALLY ADDRESSING THE QUESTION WE SHOULD BE AND ARE WE FILLING THE GAMS THAT WE NEED TO. IT WAS THE RECOMMENDATION FROM C TAC THAT WE SHOULDN'T DO THIS AGAIN SINCE WE'RE THREE TO FIVE YEARS IN THE LAST GROUP AND THAT IS IN OUR PLAN. SO THE NEXT PORTFOLIO ASSESSMENTS WOULD BE PERFORMED BY THE STEERING COMMITTEES AS I SAID BEGINNING IN 2016. AND THEY COULD BE AUGMENTED WITH ADDITIONAL EXPERT AND WE WOULD REALLY LOOK FOR A COMPREHENSIVE EXAMINATION AND PRIORITIES THAT THE STEERING COMMITTEE HAS SET, THEN THERE WOULD BE THIS SECOND GROUP, WHAT WE'RE CALLING THE OVERSIGHT ASSESSMENT GROUP UNDER THE AH PICIOUSS OF CTAC THAT WOULD BOTH LOOK ACROSS THE DISEASES AND REALLY TRY TO DESCRIBE THIS NETWORK THAT MEG WAS TALKING BERLINER--DR. BERLINERER, IN TRYING TO DO THE BEST IT COULD IN ANSWERING THE CLINICAL QUESTIONS. AND THE TYPES THINGS THEY LOOK AT IS THE QUALITY OF THE OVERALL PORTFOLIO, RECOMMENDATIONS THAT KIT ACROSS THE DIFFERENT DISEASES WHETHER'S LESSONS LEARN IN ONE DISEASE OR APPLIED IN ANOTHER AND THEY WOULD HAVE THE ABILITY TO LOOK AT THE VALUE OF THE PROCESS AND MAKE RECOMMENDATIONS FOR HOW IT SHOULD CHANGE HOW OUR REVIEW PROCESS AND ASSESSMENT PROCESS SHOULD CHANGE GOING FORWARD AND AGAIN JUST TO FINISH THIS CTAC GROUP SHOULD CONSIST OF INDIVIDUALS WHO HAVE SERVED ON THE STRATEGIC PLANNING COMMITTEE PLUS THE GROUP CHAIRS AND SOME GROUP STATISTICIANS SO THAT WE HAVE A COMMITTEE WITH BOTH EXPERTISE AND INDEPENDENCE. SO I'LL STOP HERE AND WE'LL GO ON. >> SO GREAT, THANK YOU SO I'D LIKE TO JUST STOP AT THIS POINT AND ASK, FOR ANY COMMENTS OR QUESTIONS, ESPECIALLY THE LAST SERIES OF SLIDES, IN TERMS OF WHERE THE THINKING IS CURRENTLY WITH ASSESSMENT OF THE STEERING COMMITTEES AS WELL AS THE CROSS PORTFOLIO ASSESSMENT AND THE PLANNING THAT HAS TAKEN PLACE AND THE THINKING THAT HAS TAKEN PLACE SO FAR IN TERMS WHERE NCI IS AND OBVIOUSLY A LOT OF THIS HAS BEEN AS A RESULT OF INPUT FROM THIS COMMITTEE AS WELL AS INITIALLY NCTN WORKING GROUP THAT GEORGE AND THEY'VE WORKED SO DILIGENTLY ON. AND I THINK THIS IS IMPORTANT MOMENT FOR THE COMMITTEE TO REALLY TRY TO PROVIDE ADDITIONAL FEEDBACK AND INPUT GEORGE DO YOU WANT TO LEAD OFF? >> LET ME ASK ABOUT THE SELF-ASSESSMENT PART OF THIS BECAUSE IF THE STEERING COMMITTEES WERE GOOD AT SELF-ASSESSING DO YOU THINK WE WOULD HAVE AS MANY PROBLEMs AS WE HAD WITH THE ASSESSMENT. I'M CONCERNED THAT THE LIKELIHOOD THAT PEOPLE WILL SAY, YOU KNOW WE DID A REALLY LOUSY JOB THESE LAST THREE YEARS IS LOW I THINK THERE IS REAL VALUE TO ASSESSMENT, I'M NOT VOLUNTEERING TO GIVE AN EXTRA YEAR AND HALF OF MY LIFE HERE BUT I DON'T THINK IT WOULD BE UNREASONABLE TO HAVE SOME SORT OF EXTERNAL REVIEW BUILT INTO THIS. >> SO YOU KNOW MAYBE I DIDN'T MAKE IT CLEAR BUT THE SELF-ASSESSMENT IS STEP ONE. STEERING COMMITTEES VALID TO TAKE THEIR ASSESSMENT TO THE CTAC OVERSIGHT GROUP THAT WE WERE TALKING ABOUT AND PRESENT IT TO THEM AND IT WOULD BE THE CTAC OVERSIGHT GROUP WHO WOULD ASSESS WHAT THEY THOUGHT OF THE SELF-ASSESSMENT WHETHER THEY THOUGHT IN FACT THAT IT MET THE GOALS AND IT WOULD BE THE OVERSIGHT GROUP THAT WOULD COME TO THIS BODY AND CTAC AND MAKE A PRESENT ON HOW THEY THOUGHT THE DIFFERENT DISEASES WERE DOING REGARDING THE THEIR OWN STRATEGIC PRIORITIESA WELL AS ACROSS THE PORTFOLIO REVIEW SO MAYBE I DIDN'T EMPHASIZE THAT ENOUGH BUT THERE WAS GOING TO BE THIS INDEPENDENT BODY. >> AND WOULD THERE BE A STANDARDIZED FORM AT FOR THIS ASSESSMENT BECAUSE THE OTHER THING THAT CAME OUT OF OUR ANALYSIS WAS SIMPLY HOW DISPARATE THE COMMITTEES WERE IN TERMS OF HOW THEY'RE CREATED, HOW THEY FUNCTION WHAT SORT OF APPROACH OF THE TRIALS. >> YOU MAKE A GOOD POINT THERE BUT THAT IS SOMETHING WE SHOULD TRY AND DO BECAUSE THE CTAC OVERHT GROUP HAS A MEASURING STICK AND THEY USE ACROSS THE DISEASE SO WE'RE ONLY NOW BEGINNING TO WORK ON THIS BUT THAT WOULD BE AN IMPORTANT ITEM TO MAKE SURE WE GET RIGHT. >> I THINK MY INDUSTRY PERSPECTIVE WILL COME IN HERE NOW BECAUSE I REMEMBER WHEN WE DISCUSSED IT LAST TIME THERE WAS REAL CONCERN ABOUT DOING THE EVALUATION BECAUSE OF THE AMOUNT OF WORK AND VOLUNTEER GROUP, ET CETERA AND AS SOME SENSE AS I LISTENED I THINK THERE WAS SUCCESS TO MAKE IT DIFFICULT AND IT SEEMS TO ME THAT IT'S A BIG PORTFOLIO, IT'S IMPORTANT WORK THAT'S BEING DONE AND THINGS CHANGE IN TIME AND THINGS GO WELL AND THINGS DON'T GO WELL AND I DON'T REALLY UNDERSTAND WHY THERE COULDN'T BE SOME WAY OF PUTTING TOGETHER SOME KIND OF ANNUAL REVIEW AND NOT SEPARATING STRATEGIC PLAN KNOWLEDGEYS FROM PRIORITIES ALTHOUGH I'M NOT SUGGESTING STRATEGIES BE CHANGED ALL THE TIME BUT WHY THERE SHOULDN'T BE SOME CONSIDERATION FOR A STRAIGHT FORWARD NONOWNEROUS BUT THOUGHTFUL REVIEW OF WHAT EACH OF THE--I DON'T KNOW WHAT YOU WANT TO CALL THEM, EACH GROUP, COMMITTEE, WHATEVER IT IS HOW IT'S GOING, WHAT THEIR ISSUES ARE, WHAT THEY THINK THEY'RE DOING WELL, WHAT THEY TK THEY COULD DO BETTER, WHERE THERE IS SOME EXTERNAL REVIEW AND AGAIN I'M VERY SYMPATHETIC WITHIN INDUSTRY ALSO TO THE TIME THAT SOME OF THIS CAN TAKE IF PEOPLE GET TOO FAR OF AND MAKE IT TOO BIG AND TOO COMPLICATED BUT I URGE YOU TO GIVE THOUGHT TO SOMETHING BECAUSE IT SHOULD BE AN ONGOING YEAR, IT SHOULD BE ABOUT WHAT WE'RE DOING ALL THE TIME IN AN EFORT TO MAKE SURE WE'RE DOING GOOD THINGS, BEING RESPONSIVE AND ALSO FEEDING EACH OTHER. LEARNING BECAUSE A LOT OF THIS IS NEW. WE'RE LEARNING FROM EACH OTHER AS WE GO HOW WE CAN DO IT BETTER. >> RIGHT AND I THINK MANY OF US WHO WENT THROUGH THIS ARDUOUS PROCESS THE FIRST TIME SHARE YOUR SENTIMENT IN THE SENSE THAT IF WE'RE GIVING THE DISEASE COMMITTEES, DISEASE SPECIFIC STEERING COMMITTEES TILL JUNE OF NEXT YEAR TO COME UP WITH PRIORITIES THEN WE NEED TO GIVE THEM TIME TO DEVELOP CONCEPTS AND SHOW US THAT THEY'RE ACTUALLY WORKING ON THEIR PRIORITIES AS THEY HAVE--AS THEY'VE DEFINED THEM. THAT'S WHY WE SAID THE FIRST TIME WE DO THIS WILL BE IN 2016. NOW WE WON'T BRING THE OVERSIGHT COMMITTEE OR CTAC EVERY SINGLE DISEASE COMMITTEE EVERY SINGLE TIME. WE DO THIS ON A ROLLING BASES SO THAT OVER A PERIOD OF ABOUT THREE YEARS, YOU WILL SEE EVERY COMMITTEE BEING REVIEWED AND ASSESSED AND THIS ALLOWS US TO START WITH THE ONES THAT WE BEGAN WITH ON THE WORKING GROUP AND WORK FORWARD FROM THERE. IT IS CHALLENGING TO TAKE PEOPLE FROM OUTSIDE OF THE AREA WHICH IS SORT OF WHAT YOU WANT BECAUSE IF YOU HAVE ALL BREAST CANCER FOLKS OR ALL GI PEOPLE EVALUATING THE PORTFOLIO, YOU HAVE A DIFFERENT VIEW THAN PEOPLE WHO DON'T SPEND TIME WORK NOTHING THAT AREA. BUT THE DOWN SIDE IS YOU NEED TO BRING THEM UP TO SPEED AND THINKING INTO WHY THE TRIALS THAT CAME FORWARD ONE OR TWO YEARS EARLIER WITH THE ENGINE BASE AT THAT TIME WERE SELECTED. SO I THINK WHERE WE'RE TRYING TO FIND A COMPROMISE HERE BETWEEN BEING OVERLY OPENING REMARKSEROUS AND YET MAKING SURE THAT AS YOU SAID, THAT WE DO REVIEW AND THAT PEOPLE KNOW WE ARE--WE ARE TRYING TO ACHIEVE EXTREME HIGH QUALITY TRIALS IN THIS SYSTEM AND WE EXPECT THE STEERING COMMITTEES TO MAINTAIN THOSE STANDARDS. >> SO MAYBE I'M SUGGESTING CHANGING SOMETHING THAT WE'RE NOT THINK BEING, I'M SUGGESTING AN INDUSTRY AND OPERATIONS COMMITTEE WHICH A CROSS LEVEL GROUP OF SENIOR PEOPLE AND AGAIN I DON'T THINK THAT COMMITTEE SHOULD SIT THERE AND SAY, WELL I DON'T THINK THAT'S THE STRATEGIC PLAN KNOWLEDGEY WHEN YOU'RE IN THE BEGINNING AND STARTING TO ACCRUE, BUT IT'S JUST LIKE A CHECK THE BOX OF THE BASIC THINGS. LET PEOPLE KNOW WHAT YOU'RE DOING, HOW IT FITS WITH WHAT YOU PLAN TO DO AND WHAT YOUR CHALLENGES ARE AND WHAT YOU SEE CHANGING THAT MIGHT ASSESS, YOU KNOW NOTING THE PROBLEMS THAT COULD BE COMING UP AND HOW YOU ADDRESS THEM SO I WOULD THINK OF IT MORE AS AN OPERATIONS COMMITTEE AND ANNUAL REPORT AND A LOT OF THOUGHT GIVEN TO PREVENTING THE KINDS OF PROBLEMS THAT I KNOW PEOPLE ARE CONCERNED THAT IT MIGHT BE CREATING BUT I WOULD TRY TO THINK OF IT MORE OPERATIONAL RATHER THAN OVERSIGHT AS AN OPPORTUNITY FOR PEOPLE TO WORK TOGETHER TO MAKE SURE THINGS ARE GOING IN THE WAY YOU WANT SO YOU'RE NOT WAITING THREE YEARS OR FIVE YEARS TO IDENTIFY A MAJOR ISSUE THAT YOU MIGHT HAVE FIXED OR IMPACT #-D EARLIER. SO I EMPHASIZE IT SHOULD BE SIMPLE AND STRAIGHT FORWARD AND MORE OPERATIONAL. >> SO THIS DISCUSSION REALLY FOR ME EXEMPLIFIES THE TENSION BETWEEN TOP DOWN AND BOTTOM UP APPROACHES AND FINDING THE RIGHT BALANCE IS SOMETHING YOU'RE ALL WORKING HARD TO ACCOMPLISH BUT I WOULD SUSPECT THAT IF THERE'S BEEN A STRATEGIC OVERSIGHT PROCESS IN THE TYPE YOU DESCROIB IN 2009 OR 2010, THE WORD PD ONE OR CTLA FOUR WOULDN'T HAVE EVEN BEEN ON THE RADAR AND I DON'T KNOW THAT THERE'S--I DIDN'T HEAR THERE WAS A STRATEGY IN PLACE FOR INCORPORATING THESE NEW CONCEPTS AND IDEAS AS EFFECTIVELY AS POSSIBLE INTO WHATEVER'S STRATEGIC OVERSIGHT PROCESS MIGHT BE PROVIDED AND ONE OF THE THINGS I DIDN'T SEE WAS WHERE THE TRANSLATIONAL SCIENTIST INPUTS MIGHT BE INCORPORATED INTO THIS KIND OF OVERSIGHT SO THAT NEW OPPORTUNITIES FOR LARGER SCALE EVALUATION WEREN'T BEING MISSED AND THERE WASN'T A DELAY IN TAKING EXCITING NEW CONCEPTS FORWARD. PARTICULARLY AS MANY OF THESE NEW CONCEPTS ARE NOT GOING TO INVOLVE NECESSARILY THE LARGEST POTS OF PATIENTS THAT ARE AVAILABLE BUT RATHER SOME OF THE LESS COMMON DISEASES. SO HOW DO YOU THINK YOU MIGHT BE TILE INCORPORATE THOSE NEW TRANSLATIONAL CONCEPTS AND AND A ROW FOR INSPIRED OBSERVATIONS AND INSPIRED NEW CONCEPTS TO ACTUALLY AGAIN ATTRACTION FOR THIS. >> THE STEER'S COMMITTEE JUST NOW GETTING TOGETHER AND TALK ABOUT STRATEGIC LEVELS AND THE LEVEL OF GRANULARITY THAT THEY'LL DO THAT IS UP FOR DEBATE. IT MAY BE SOMETHING MUCH MORE GENERAL THAN WHAT YOU'RE THINKING IN THE SENSE THAT IT MAY BE THAT THAT SAY PANCREATIC CANCER WE NEED GOOD SYSTEMIC THERAPY BECAUSE YOU KNOW WE DON'T HAVE ANY, AND THEREFORE ANY GOOD TRANSLATIONAL IDEA IS OBVIOUSLY ON THE TABLE WRASSE IT MIGHT BE THAT IN BREAST CANCER WE DON'T NEED TO CONCENTRATE OR DO VERY, VERY LARGE LOCAL THERAPY TRIALS AS AN EXAMPLE BECAUSE MANY THOUSANDS OF PATIENTS AND LAST MANY YEARS SO THE GROUP WAS ASKING FOR GUIDE LINES SHOULD THEY WHEN THEY GET THESE WITH INVESTIGATORS GO SPEND A YEAR DEVELOPING THIS CONCEPT AND IT WOULD HELP THEM, THEY ACTUALLY SAID TO KNOW WHAT THE PRIORIES OF THE TEARING COMMITTEES WERE. BUT I DON'T THINK DOWN TO THE LEVEL OF, YOU KNOW WE WANT YOU TO WORK IN THIS SPECIFIC THERAPY NOW OR TOET DETRIMENT OF ANYTHING NEW THAT WOULD BE DEVELOPED LIKE THE IMMUNOTHERAPIES CAN HAVE BECOME SO HOT NOW BUT EVEN WITH THAT SAID, I GUESS THE SAVING GRACE IS THE PEOPLE ON THESE COMMITTEES ARE SENIOR LEADERS, EXPERTS IN THEIR PARTICULAR AREA, THERE ARE TRANSLATIONAL SCIENTISTS ON EACH ONE OF THESE STEERING COMMITTEES, AND I THINK--I WANTED TO MAKE SURE THAT I EMPHASIZE THAT EVEN IF A GREAT IDEA COMES IN AND IT'S NOT IN THE STRATEGIC PRIORITIES IF IT'S A GREAT IDEA, I THINK IT'LL BE WELL RECEIVED BY THE COMMITTEE. >> SO I HAVE TWO QUESTIONS. ONE IS FOR DR. MOONEY, AS WE GO OVER THE PRECISION MEDICINE AND OTHER TRIALS AND MATCH TRIAL, ANY PLAN OR ANY IDEA ON HOW THIS IS DONE, IS IT CENTRALIZED MOW TO MAKE IT UNIFORM, QUALITY CONTROL? >> YEAH, I THINK IT'S A LARGE PART OF ANY OF THE TRIALS, FOR EACH OF THEM IT DEPENDS ON THE OPPORTUNITIES STATE OF THE SCIENCE OF THAT TIME, THEY'LL ALL BE DONE CENTRALIZED IN SOME CENTRALIZED FASHION, ALCHEMIST FOR MATCH AND FOR LUNG MAP AS WELL AS PEDIATRIC MATCH AND DEVELOPMENT BUT IT MIGHT BE DONE SLIGHTLY DIFFERENTLY AND LABS DESPENDING ON THE STATE OF THE SCIENCE AND THE CLINICAL SETTING BUT OBVIOUSLY THAT'S A HUGE PORTION OF THE DEVELOPMENT AND DESIGN OF THE TRIAL. >> MY SECOND IS MORE GENERAL BUT WITH THE 10 GROUPS, NOW IT'S FIVE GROUPS, AND OBVIOUSLY, THE TENDENCYS ARE GONE, EFFICIENCIES ARE GONE, ANY IDEA HOW MUCH MONEY ARE WE SAVING BY DECREASING THIS TO REMOVING THE REDUNDANCIES? >> HOW MUCH MONEY ARE WE SAVING? >> HOW MUCH MORE MONEY IS AVAILABLE TO DEVELOP IT? >> YOU KNOW I THINK IT'S HARD TO MAKE THAT CALCULATION. AND WE HAVE VERY DETAILED SLIDES ACTUALLY IN A BREAK DOWN OF THE FUNDING BEFORE AND THE COOPERATIVE GROUP SYSTEM AND HOW IT'S DISTRIBUTESSED NOW IN THE NCTN SYSTEM ON THE WEB SITE AND THAT WAS PRESENTED AT THE IN, CAB MEETING AS WELL YOU KNOW IT'S HARD TO GET THAT EXACT CALCULATION BUT WHAT WE'VE BEEN ABLE TO DO WITH THE COMBINATION OF DECREASING THE REDUNDANCY AND THE ACCRUAL ONLY SLIGHTLY THAT WE'RE ABLE TO FUND THE LEAD ACADEMIC SITES AT A HIGHER RATE, WE'RE ABLE TO FUND COMPONENTS OF THE TRIALS NOW A BIT MORE, BEFORE IT WAS JUST ONE PRICE FOR EVERYTHING, NOW WE'LL PAY SEPARATELY FOR THE BIOSPECIMENS, SEPARATELY FOR CREEPING SO WE CAN PROVIDE SUPPORT AND WE'LL HAVE TO SEE HOW THAT PLAYS OUT. BUT AT LEAST THE PLAN FOR THIS YEAR, THE WAY WE FUNDED THE BUDGET AND THE ACCRUAL THAT WE'RE SPECTING, WE EXPECT NOT TO HAVE ANY FUNDING PROBLEMS, I KNOW THERE WERE A LOT OF ISSUES BROUGHT UP INITIALLY BUT AT LEAST ALL OUR PROJECTIONS WHERE ALL THE TRIALS THAT WERE OPENED AND NONE HAVE CLOSED BECAUSE OF FUNDING ISSUES. SOME HAVE CLOSED BECAUSE OF POOR ACCRUAL, NEW SCIENTIFIC INFORMATION, YOU KNOW INTERIM ANALYSIS, BUT, SO, AND I THINK THE GREAT ADVANTAGE NOW OF HAVING A REALLY INTEGRATED SYSTEM WITH REALTIME MONITORING IS THAT WE CAN ACTUALLY KNOW WHAT WE'RE DOING AND SO, IT HELPS US PLAN MUCH BETTER AND HELPS US MAKE SURE THAT WE CAN FUND WHAT WE WERE DOING AT THE LEVEL THAT WE WANT TO. SO I WANTED TO FOLLOW UP ON THE MEDICINE FROM THAT LAST PIECE, FROM THE GENERAL SAMPLING FROM THE TWOF YOU, YOU GOT THIS INCREDIBLY WELL ORCHESTERATED DISEASE SITE ORIENTED NCTN AND STEERING COMMITTEES AND ALSO OF A SUDDEN YOU'RE INTRODUCING THESE TARGETS AND STUDIES THAT ARE REALLY DRIVEN BY TARGET THAT SHOULD VERY LIKELY CUT ACROSS THOSE DISEASE SITES. SO HOW DO YOU DO THAT, HOW DO YOU TAKE ADVANTAGE OF THE NEW APPROACH AND TAKE ADVANTAGE OF YOUR EXISTING SYSTEM WITHOUT HAVING TO CREATE A ANOTHER COMPLETELY NEW AND DIFFERENT SYSTEM TO HANDLE PRECISION MEDICINE. , THE NICE THING YOU HAVE IN THIS SERIES OF TRIALS THAT MEG PRESENTED, HAVE YOU NCI MATCH WHICH IS HISTOLOGY AGNOSTIC. YOU KNOW IT'S REALLY ANY PATIENT WITH ADVANCED CANCER SOLID TUMOR LYMPHOMA IN THAT PARTICULAR TRIAL WHO HAS THE RIGHT PARTICULAR MOLECULAR ALTERATION REGARDLESS OF THE HISTOLOGY WOULD GET A TARGETED DUG TAKEN--THEY WE HOPE WILL INTERFERE WITH THAT TARGET. AND WE--WE DIDN'T HAVE ANY PROBLEM BRINGING THAT THROUGH THE NCTN SYSTEM, THE--IF WE END UP DOING MORE OF THOSE TYPES OF TRIALS IN THE FUTURE, IF IT SORT OF SUPERSEEDS HISTOLOGY, WE MAY HAVE TO THINK OF DIFFERENT STEERING COMMITTEE INFRASTRUCTURE BUT AS YOU SAW HISTOLOGY DOES COUNT AND WE HAVE LUNG CANCER TRIALS THERE WITH ARE WHERE AS WE'RE LEARNING ABOUT THIS, IT ISN'T--IT ISN'T GOING TO BE AN ALL OR NONE PHENOMENA. THERE WILL BE ALTERATIONS THAT DO CUT ACROSS AS WE'VE SEEN ALREADY BUT SOMEWHERE THE POTENTIAL FOR OUTCOME. >> AS WHAT MARGARET WAS TALKING ABOUT, WE ARE A DISEASE ORIENTED SYSTEM AND IT MIGHT BE GOOD TO PERIODICALLY REVISIT THAT AS THIS PROCESS EVOLVES FOR PRECISION MEDICINE. >> YEAH, I THINK WE NEED A QUESTION OR TWO AND THN MOVE ON. >> SO THE INTENTION IS THAT THIS COULD GO ON FOREVER? BECAUSE THERE'S ALWAYS GOING TO BE NEW BASKET EXPS DRUGS TO PUT IN THOSE BASKETS. HAD YOU GIVEN THOUGHT TO--DOES THIS GO ON TILL WE ALL RETIRE? HOW ARE YOU GOING TO EVALUATE SUCCESS OR FAILURE IN THE LONG RUN AND TELL EVER SUN SET? >> ALL RIGHT, SO I REALIZE MOST PEOPLE THINK, NO GOVERNMENT PROGRAM EVER ENDS BUT WE HAVE ACTUALLY THE TRIAL IS DESIGNED TO SCREEN 3000 PATIENTS, THAT GET IT WE HOPE IN THE DIFFERENT ARM AND THE TRIALS WE HAVE SO IT'S ALREADY SET UP TO STOP, YOU KNOW AT A CERTAIN POINT. IT'S ALSO A FUTILITY RULE IN THERE SO IF WE CREEP A CERTAIN NUMBER OF PATIENTS AND WE DON'T FIND ENOUGH WITH MOLECULAR ALTERATIONS TO ACTUALLY PUT THEM INTO ENOUGH TRIALS THAT ACTUALLY WILL STOP SOONER BUT THE MAXIMUM RIGHT NOW IS TO SCREEN UP TO 3000 PATIENTS AND HOPEFULLY GETTING ABOUT A THOUSAND OF THEM ON TO TRIAL. >> I UNDERSTAND THAT. BUT-- >> OH, SORRY. >> BUT I COULD IMAGINE A COUPLE YEARS FROM NOW, YOU'VE HAD A COUPLE HITS AND A COUPLE OF THESE BASKETS, IT'S A PROMISING APPROACH. IT WILL--THIS WILL BE A TRIAL THAT WILL BE WELL LOVED IN THE COMMUNITY. IS THERE ANY REASON NOT TO CONTINUE IT TWO OR THREE YEARS FROM NOW WHEN YOU HIT THE 3000 MARK. >> I WAS JUST GOING TO SAY, MAYBE--I THINK WE'LL ALL HAVE TO EVALUATE IT AND SEE IF IT DOES DISCOVER WAWE'RE HOPING IT WILL AND IF IT DID AND GAVE A LOT OF LEADS TO PHASE TWO TRIALS THAT LED TO THERAPIES THAT WERE USEFUL THEN I THINK EVERYBODY WOULD LIKE THIS APPROACH AND WANT TO CONTINUE IT WITH SCREENING TECHNOLOGY THAT BECAME AVAILABLE BUT THE PROOF WILL BE IN THE PUDDING SO TO SPEAK. WILL WE ACTUALLY FIND NEW THERAPIES IN THE NEW TRIALS. >> THAT'S WHY IT'S BEEN SET UP WITH THE PARAMETERS, RIGHT NOW WE ANTICIPATE SIX OR SEVEN YEARS EVERYTHING WITH THE 3000, YOU KNOW NOT ACCRUAL BUT TO GET TO THE END POINTS BUT AS JEFF SAID IT'S ALSO DESIGN THAD IF WE FIND SOMETHING FOR THAT AGENT OR HISTOLOGY THERE WOULD BE TRIALS OFF OF IT OBVIOUSLY IF NEW SEPARATE TRIALS DEPENDING ON WHAT WE DISCOVER BUT WE'LL HAVE TO SEE WHETHER IN THAT PERIOD OF TIME WE FIND THIS A PROFIT AND PRODUCTIVE WAY TO DO DRUG SIGNAL THINKING AND DRUG DISCOVERY. >> THANKS IS THERE AN EXPECTATION OF THE DISEASE GROUPS AS THEY DEVELOP--EXCUSE ME--PRIORITIZE PLANS OR PRIORITIES TO SEEK APPROVAL FROM THE FDA TO BRING IN EXPERTS ABOUT THOSE PRIORITIES AS THEY GET STARTED? >> WELL THERE ISN'T A FORMAL PLAN, WE DO HAVE FDA OBSERVERS ON THE STEERING COMMITTEES AND AS THEY HAVE INSIGHTS INTO THIS, IT MIGHT BE ABLE FOR THEM TO TALK ABOUT THIS ASPECT OF THINGS WHERE IT'S MORE DIFFICULT ON SPECIFIC TRIALS, BUT WE WELCOME PEOPLE WHO PARTICIPATE IN THE STEERING COMMITTEE PROCESS. RICK, DO YOU WANT TO SAY ANYTHING ABOUT IT? >> WELL WE HAD INPUT ON THE TRIALS YOU MENTION AND WE ARE LOOKING AT THEM OBVIOUSLY AND PROVIDING COMMENT AND IT WAS THE LONG MAP PROTOCOL AND IT WAS DESIGN WIDE THE TRIAL AND GRAPHIC REVIEW OF THE TRIAL. SO WE HAVE REORGANIZED SOME OF OUR APPROACHES WHEN WE HAVE THESE UMBRELLA BASKET TRIALS TO LOOK AT ONE MEDICAL REVIEWER AND FOR ONE LOOKING AT THESE TRIALS AND IT DOESN'T LEAD TO CONFUSION SO THERE'S A NEED TOO ORGANIZE OUR APPROACHES THAT MIGHT HAVE MULTIPLE I& Ds ASSOCIATE WIDE THEM. >> THE REASON I ASK THAT QUESTION IS FROM AN OUTSIDE PATIENT PERSPECTIVE, IT APPEARS THAT THE NCI HAS GREAT CAPACITY TO ON PARTICULAR THINGS AND FDA HAS BIG THINGS AND WHEN THEY COME TOGETHER AND DEVELOPING CLINICAL TRIALS IS ONE EXAMPLE WHERE WE HAVE TERRIFIC EXPERTISE IN BOTH AGENCIES. >> THANK YOU. >> THANKS SO WE WILL MOVE ON TO DR. Mc CASKILL-STEVENS WHO WILL GIVE US THE UPDATE ON NCORP. >> THANK YOU FOR GIVING ME THE OPPORTUNITY TO PRESENT THE RESEARCH PROGRAM ON THE NCORP, I AM PRESENTING ON BEHALF OF CANCER PREVENTION, POPULATION SCIENCES AND TREATMENT DIAGNOSIS AND CENTER TO REDUCE CANCER DISPARITY. SO THE NCORP PROGRAM WAS ALSO UNDER AGGRESSIVE TIMELINE TO GET THE PROGRAM UP AND STARTED ABOUT TWO AND HALF YEARS AGO AND NCI BEGAN THE PLANNING FOR NCORP THAT INCLUDED A BROAD SPECTRUM OF SELECTING INPUT FROM BOTH THE PUBLIC AND SCIENTIFIC COMMUNITY. MOVING THROUGH THE VARIOUS PROCESSES FOR THE CONCEPT APPROVAL LEADING TO THE APPROVAL BY THE BOARD OF SCIENTIFIC ADVISORS IN JUNE OF 2013. WE THEN DEVELOPED A FUNDING OPPORTUNITY ANNOUNCEMENT THAT WAS RELEASED AND PEER REVIEWED IN THE SPRING AND NCORP WAS LORNED ON AUGUST 1 OF THIS YEAR. NOW IN ADDITION TO WHAT I'M GOING TO SHARE WITH YOU I WILL INFORM YOU OF WHAT THEY ARE GOING TO BE LAUNCH, SO NCORP IS PUBLISHING TRIALS, THESE TRIALS ARE BEING ACCESS BIDE THE COMMUNITY ENCLUED TRIALS FOR PREVENTION, CONTROL, QUALITY OF LIFE, COMPARATIVE EFFECTIVENESS AND SCREENING. WE HAVE NOT HAD--THERE HAVE BEEN SIGNIFICANT GAPS IN OW CANCER CARE DELIVERY TAKES PLACE IN THE COMMUNITY SETTING AND THEREFORE WE HAVE EXPANDED THE RESEARCH SCOPE WITHIN NCORP AND CANCER DELIVERY IN THE SETTING SO THIS ALLOWS US TO MOVE BEYOND THE PATIENTS TO LOOK AT OTHER CRITICAL FACTORS INCLUDING PROVIDERS AND ORGANIZATIONS AND HOW THEY INFLUENCE THE OUTCOMES IN THE CANCER PATIENTS. WE HAVE HAD A FOCUS ON ENROLLING AND RETENTION OF AND CONTINUE WITH THE PROGRAM PREVIOUSLY BUT NOW WE HOPE FOR THE RESEARCH QUESTIONS AND CLINICAL TRIALS AS WELL AS CANCER DELIVERY THAT WILL HELP US PERHAPS COME UP WITH INTERVENTIONS DISPARITIES IN OUR OUTCOME AND NOW WE HAVE CONTRIBUTED TO EXTREME AND TRIALS AND OVER THE LAST THREE DECADES AND WE WILL CONTINUE TO ENROLL PATIENTS AND IMAGING STUDIES. WE HAVE HAD A SUCCESSFUL MODEL AND ACTIVE PARTNERSHIP AND IT IS IMPORTANT THAT WE HAVE--HAVE APPEALING OPPORTUNITIES FOR INCREASED PARTICIPATION BY EXPERTS AS WE MOVE INTO A NEW AREA OF CANCER RESEARCH AND IMPORTANTLY WE HOPE TO HAVE OPPORTUNITIES THAT ARE CONDUCIVE FOR FACULTY WHO ARE BRINGING TO THE TABLE TRAINING AND TECHNOLOGIES THAT ARE VERY IMPORTANT FOR US. OUR PROGRAM WILL HAVE THREE COMPONENTS, ONE WILL BE SERVING UNDERSERVED COMMUNITIES AND POPULATIONS, IT WILL PROVIDE GUIDANCE FOR RURAL POPULATIONS THAT ARE UNDERREPRESENTED AND UNDER SERVED AS WELL AND THE RESEARCH BASIS SERVE AS THE ORGANIZATION THAT DEVELOP THE CONCEPT AND PROTOCOLS TO BE IMPLEMENTED IN THE COMMUNITY SETTING AS WELL. SHOWN HERE ARE THE SITES AND 12 MINORITY AND UNDERSERVED SITES AND WE HAVE THE SEVEN RESEARCH BASIS THAT ARE IN WILL YELLOW SQUARES. WE HAD VARIOUS AND DIVERSE ORGANIZATIONS THAT ARE WITHIN NCORP. AND WE HAVE ORGANIZATIONS THAT TRAVERSE FIVE STATES OR SO. WE HAVE INTEGRATED ORGANIZATIONS THAT ALSO PROVIDE A SPECTRUM OF DISCIPLINE IN THE COMMUNITY SETTING AND WE'VE BEEN ABLE TO RETAIN SOME OF THE SMALLER PRACTICES AS WELL. NOTICE IN THE CIRCLES OR ROCKY MOUNTAIN PLAINS TO DEMONSTRATE THAT ALTHOUGH IT LOOKS THERE IN THAT PART OF THE COUNTRY BUT THESE REFLECT THE PACT THAT THERE ARE MULTIPLE COMPONENTS THAT PROVIDE INCREASED ACCESS TO CLINICAL TRIALS IN THOSE AREAS. AND IN FACT THERE ARE COMPONENTS WITHIN NCORPS, WE HAVE EIGHT HEALTHCARE SYSTEMS, SOME OF THE CLASSIC SYSTEM SUCH AS KISER AND FOCUSED ON THE WEST COAST AND COLORADO AND HAWAII AND INCLUDED IN THE EIGHTH HEALTH SYSTEMS I LISTED HERE IS ONE THAT LED INTO PEDIATRIC FOCUS AS WELL, MANY OF ACTIVITIES EMERGENCIERS AND ACACQUISITIONS, IN RESPONSE TO THE FUNDING COMMUNITY IS THAT LEGACY SITES CONSOLIDATED AND MERGED. THERE WERE SEVEN OF THEM THAT ARE BEING SUPPORT INDEED NCORPS. EACH OF THE COMMITTEE SITES WAS REQUIRED TO IDENTIFY AT LEAST ONE COMPONENT THAT WOULD PARTICIPATE IN THE NEW COMPONENT OF NCORPS, THE CANCER CARE DELIVERY RESEARCH AND THERE ARE OVER 200 NOW WHICH FAR EXCEEDS THE 46 PROGRAM. SO THIS IS LARGER INTEGRATE THE SYSTEM INCLUDES ALL OF THEIR SITES SUCH AS COLLECTING DATA CLAIMS THROUGH THEIR SYSTEM, I LISTED HERE THE FOUR BROAD AREAS OF THE RESEARCH THAT ARE INCLUDED WITH IN THE NCORPS THAT INCLUDE REDUCTIONS IN RISK AND INCIDENCE OF CANCER AND CO-MORBIDITIES AND EVALUATE DIAGNOSE AND I GUESS REDUCTION IN RECURRENCES AS WELL AS OUR EXTENSIVE QUALITY OF LIFE IS IT THES EMBEDDED IN OUR TREATMENT TRIALS. ONE OF THE OPPORTUNITIES THAT WE HAVE IS THAT THEY DO NOT FOCUS ON THE FOUR AREAS OF RESEARCH ALL AT ONCE, THEY SELECT THOSE ACTIVITIES I HAD LISTED HERE THE SEVEN RESEARCH BASIS I DO NOTE THAT BEFORE THE FOUR ADULT NCFNs IN THE ONE PEDIATRIC DID APPLY AND FUNDED TO CONDUCT THE RESEARCH FORECANCKER CONTROL PREVENTION AND IN ADDITION WE HAVE TWO COMMUNITY CANCER CENTERS THAT DO CANCER CONTRO PREVENTION. I LISTED HERE THE THE CONTACT PIs LISTED FIRST AND THIS DID TAKE THE OPPORTUNITY TO USE THE MULTIPLE PIOPTION IN THE PROGRAM. >> OUR FOCUS WE HAVE BEEN AT THE HELM OF DOING STUDIES THAT HAVE HELPED TO AMELIOR EIGHT SYMPTOMS AND TOXICITIES FROM TREATMENT WE NOW FOCUS ON IDENTIFYING MECHANISMS AND AREAS OF AND WERE BIOMARKERS OF RISK AND TREATMENT RELATED TOX ISOTOPITYS AND WE HEAP WE CAN MOVE IN FIELD FORWARD SO WE WILL BE IN ALYMEINMENT AND MOLECULARLY TARGETED AGENTS AS BEING DONE IN THE TREATMENT AREASON A. WE ARE INTERESTED IN THOSE DISEASES FOR WHICH WE HAVE CURATIVE INTENT AND WE DO NOT HAVE STRONG EVIDENCE OF HOW THOSE PATIENTS ARE GOING TO ORBED GO SURVEILLANCE AT MARKERS IMAGING STUDIES. AND THIS IS THE ONE WHERE WE HOUSE THE CARCINOMA WITHIN OUR PORTFOLIO AND WE WILL CONTINUE TO ENHANCE OUR ACCRUAL AS WELL AS INTEGRATE STUDIES INTO THOSE AREAS THAT I MENTIONED BEFORE. OUR PARTNERSHIP HAS INTEREST IN OVERDIAGNOSIS AS WELL AS UNDERDIAGNOSIS WHICH WAS MENTIONED THIS MORNING. THE STEERING QUALITY OF LIFE COMMITTEE WAS ESTABLISHED TO DO RESEARCH IN OUR DIVISION AND WILL CONTINUE INTO NCORP AND I WANT TO SHARE WITH YOU A FEW COMMENTS AS IT RELATES TO HOW THE DIRECTION OF OUR PORTFOLIO IN TERMS OF MECHANISTIC APPROACH TO THESE AREAS. THEIR LEADERSHIP IS--THERE'S NEW LEADERSHIP, CO-CHAIRS KAREN FROM THE UNIVERSITY EVER ROCHESTER CANCER CENTER, AND DAB FROM THE UNIVERSITY OF MICHIGAN. AND IN ORDER TO ADDRESS THE ISSUES RELATED TO THE MECHANISTIC MARKERS AND BEING ABLE TO IDENTIFY VALIDATE AND AN LAZE THEME, WE HAVE ACTIVITIES FROM THE FOOD AND DRUG ADMINISTRATION AS WELL AS ONCOLOGISTS. THERE ARE NEW ACTIVITIES WITHIN THE STEERING COMMITTEE. THERE WAS A WORKING GROUP TO EXPLORE FUNDING MEXANISTIC STUDIES FOR SYMPTOM MANAGEMENT AND WE HAVE WEBINARS, A SERIES OF SEVEN THAT HAVE BEEN DEVELOPED AND PLACED ON THE WEB, IT'S AN INTERNATIONAL COLLABORATION WORRY SOCIETY OF QUALITY OF CARE RESEARCH AND NCI AND WILL ALLOW INVESTIGATORS TO GO ON THE WEB AND BETTER UNDERSTAND DESIGN FOR INTEGRATING PATIENT REPORTED OUTCOMES INTO CLINICL TRIALS AS WELL AS SOME STANDARDIZATION OF END POINTS. SO WE CURRENTLY HAVE NOW 50 TRIALS THAT ARE ACTIVE OR APPROVED AND THIS INCLUDES THROUGH THE LEG ASTERISKSY STUDY THAT ARE BEGUN WITHIN THE PREVIOUS PROGRAM THAT ARE TRANSITIONED INTO NCORPS. THOSE THAT WERE FOOD AND PREVIOUSLY PUT ON HOLD, WE HAD A HIATUS DURING WHICH TIME OUR INVESTIGATORS WERE ACTIVELY RESPONSING AND MAKING TRANSITION INTO NCORPS AND WE ARE NOW OPEN FOR BUSINESS AND HAVE RECEIVED IN FACT NEW CONCEPTS COMING INTO THE NCORPS. WE HAVE NOW INCREASE IN CARDIO ONCOLOGY, THERE'S A TASK FORCE IN NCORPS TO PRIORITIZE RESEARCH IN THIS AREA ACROSS THE RESEARCH BASIS. WE ARE ALSO CONDUCTING WEBINARS TO INTRODUCE FROM THE DIVISION TREATMENT AND DIAGNOSIS PRECISION AND FORT FOLIO WE HEARD ABOUT THIS MORNING SO OTHER COMMUNITY INVESTIGATORS ARE ORIENTED AND CAN ASK QUESTIONS ABOUT HOW THEY WILL INTEGRATE THESE STUDY INTO'S COMMUNITY PRACTICE. THE NCI CONCEPTUALIZES THREE MAJOR CATEGORIES IN THE AREA OF CANCER CARE DELIVERY RESEARCH. THE FIRST IS DESCRIPTIVE OBSERVATIONAL STUDIES IN WHICH WE WILL LOOK TO HAVE A BETTER UNDERSTANDING OF THE LANDSCAPE, THE PREVALENCE AND VARIABILITY OF PROCESSES AND APPROACHES IN CLINICAL AND HOW THEY EFFECT CLINICAL OUTCOMES. AND THEN TAKING IT TO THE NEXT LEVEL OF ANALYTICAL OBSERVATIONAL STUDIES WHERE WE LOOK AT MULTILEVELS, THE PATIENT, PROVIDER AND ORGANIZATIONS INFLUENCES ON THOSE OUTCOMES AND HOPEFULY TO DEVELOP INTERVENTIONS THAT WILL HELP US IMPROVE THE OUTCOMES AND QUALITY OF CARE FOR THOSE PATIENTS. AND THE AREAS HOW WE WILL INTEGRATE THEM AND THE FORCE OF OUR EXPERTISE, AS I MENTIONED WE ARE COLLABORATING WITH THE HAVE TO REDUCE CANCER DISPARITY, IS LEADING AND INITIATIVE WITH THE FOUR MAJOR RESEARCH ORGANIZATIONS AND THE AMERICAN ASSOCIATIONS OF CANCER RESEARCH AND AMERICAN SOCIETY FOR CLINICAL ONCOLOGY, AND THE AMERICAN CANCER SOCIETY FOR A JOINT POSITION STATEMENT ON CANCER DISPARITIES WHICH WE HOPE WILL HELP PRIORITIZE AND RESEARCH THEM AS WE INTEGRATE THEM INTO OUR PROGRAM AS WELL AS HOPEFULLY TO HAVE A BROADER INFLUENCE AS WELL. WE THINK THERE ARE OPPORTUNITIES IN IN AREA. ALL OF OUR AREAS HAVE DESIGNATED COMMITTEES TO SOME EXTENT THAT ADDRESS DISPARITY SO WE INCREASE POWER AND ANALYSIS AS WELL AS DESIGN OF STUDIES BY COALESCING THE COMMON INTEREST FROM THOSE RESEARCH BASES. SO ALL OF THIS, RESULTED IN FUNDING FOR NCORPS FOR THE FISCAL YEAR 2014 OF 93.1 MILLION DOLLARS. THERE WAS APPROXIMATELY 3.9 MILLION ALLOICATIONS FOR THE WORK THAT WE SHARE WITH THE DIVISION OF CANCER TREATMENT AND DIAGNOSIS FOR DRUG DISTRIBUTIONS FOR MONITORING, ET CETERA. AND JUST IN THE NEXT BLOCK YOU SEE HOW THAT WAS BROKEN DOWN WITH THE TWO COMMUNITY SITES AS WELL AS THE RESEARCH BASIS WITH 50.3 MILLION FOR THE COMMUNITY SITES FOR IN YEAR AND 42.8 FOR THE RESEARCH BASIS. AND IN ADDITION. IN ADDITION, THERE'S ONE TIME YEAR FUNDING AND THE AMOUNT OF 5.2 MILLION WHICH WAS DISSEMINATED TO THE COMMUNITY BASE TOYS ENHANCE CLINICAL TRIAL ACCRUAL. SO POST THE LAUNCHING ONE OF THE FIRST ACTIVITIES THAT TOOK PLACE WAS BRINGING TOGETHER THE RESEARCH BASIS AND SOME OF THE COMMUNITY SITES TO HAVE A TWO-DAY PLANNING MEETING TO BEGIN THE FOUNDATION FOR THE WORK FOR THE NEW COMPONENT OF NCORPS, THE CANCER CARE DELIVERY ACTIVITY. THE GOAL OF THIS MEETING WAS TO BEGIN THE DISCUSSIONTHE PRIORITIES THIS, IS A NEW COMPONENT. THIS WAS A VENUE IN WHICH THE RESEARCH BASIS HAVE AN OPPORTUNITY TO SHARE THE AREA OF INTEREST TO DESCRIBE IN THEIR COMPETITIVE APPLICATIONS AND THERE WAS ALSO A TIME TO BEGIN TO TALK ABOUT THE COORDINATING COMMITTEE WHICH I WILL MENTION MOMENTAR ILLEGALS SCHETALK ABOUT THE INFRASTRUCTURES WITHIN THE RESEARCH BASIS AND IN ADDITION TO THE RESEARCH STRUCTURE CAPACITY FOR THE COMMUNITY SITES THAT WERE FUBBEDDED. SO IN ATTENDANCE WERE THE RESEARCH BASIS AND THEIR SELECTED LEADS FOR CANCER CARE DELIVERY RESEARCH IN ADDITION TO THE COMMUNITY SITES THAT HAVE BEEN DESIGNATED OR DESCRIBED EXPERIENCE IN THEIR APPLICATIONS IN CANCER CARE DELIVERY RESEARCH. AND THERE WAS CLEAR EVIDENCE OF INNOVATION AND EXPERTISE AND SEVERAL RESENTATIONS BY THE DIVISION OF CANCER CONTROL AND POPULATION SCIENCES, THAT SORT OF DESCRIBED THE LANDSCAPE HAVING REVIEWED THE INSTITUTES OF MEDICINE REPORT, HAVING LOOKED AT THEIR OWN PORTFOLIO AS WELL AS IN LITERATURE, THE REVIEW SET THE STAGE FOR SOME OF THE DISCUSSIONS AND THERE WERE SEVERAL BREAK OUTS OF TOPICS OF WHICH I HAD LISTED ON THE SLIDE. >> THE CANCER CARE COORDINATING COMMITTEE HAS BEEN ESTABLISHED TO PROMOTE AND COORDINATE ACROSS YCORP SCIENTIFIC AREAS SO THAT THE RESEARCHER BASIS AND COMMON INTEREST THEY CAN BEGIN TO WORK WITH THIS AND INTERE INTO THE INFORMATION THAT WILL GO INTO THE NEXT COMMITTEE THEY WOULD DESCRIBE, THE COORDINATING COMMITTEE WILL DEVELOP THE OPERATIONAL PROCEDURES FOR THE DEVELOPMENT, REVIEW AND IMPLEMENTATION OF CANCER CARE DELIVERY WITHIN NCORPS, THEY WILL ALSO IDENTIFY OUTSIDE SOURCES OF FUNDING AND HOW THAT MIGHT BE VIEWED WITHIN NCORPS AND WHAT WOULD BE APPROPRIATE FOR NCORPS AND IMPORTANTLY TO STABBED ARDIZE THE VARIOUS ASPECTS FOR DATA DEFINITIONS, COLLECTIONS OF TWO TUBES AND PROCEDURES AND THE AUDITS AND THEY WILL ALSO DETERMINE THE DATA THAT EXISTS AND CONFIRM THE INFORMATION THAT WAS REPORTED AND ALSO TO LOOK AT THOSE INSTITUTIONS THAT ACTUALLY CONSOLIDATED TO SEE HOW THEIR INFRASTRUCTURES ARE GOING TO BE AVAILABLE FOR AND WHAT CAPACITY IS AVAILABLE FOR THE STUDY. WE HAVE SELECTED THE COMMITTEE CO-CHAIRS THEY ARE JAN BUCKENER FROM THE MAYO CLINIC REPRESENTING THE ALLIANCE. RUTH CARLOS FROM THE UNIVERSITY OF MICHIGAN, AND SCOTT RAM RAMSEY FROM THE HUTCHISON IN SQUAB, THEY WILL HAVE MEMBERS FROM THE RESEARCH BASE AND ONE SHOULD BE THE CANCER CARE DELIVERY RESEARCH EXPERT, FOUR MEMBERS FROM THE COMMITTEE OF SITES, THREE FROM THE MINORITY UNDERSERVED AND THERE WILL BE NCI REPRESENTATION AS WELL. THE SECOND COMMITTEE WITH THE NCORPS WOULD BE THAT FOR CANCER CARE DELIVERY RESEARCH. IN THE PLANNING IT WAS MADE VERY CLEAR THAT THERE WOULD BE A REQUIREMENT FOR A STANDING COMMITTEE THAT WOULD HAVE COST DISEASE REPRESENTATION. THAT WOULD HAVE THE STATISTICAL EXPERTISE FOR LARGE DATA SET AAS WELL AS HAVING THE SATTA DETAILS SUFFICIENCY FOR MEETING THE DEMANDS OF THE CONCEPT THAT WOULD BE DEVELOPED. SO THE NCORP STEERING COMMITTEE WOULD ADHERE TO AWFUL THE GOALS OF THE DISEASE AND NONDISEASE COMMITTEES SUCH THAT STRATEGIC SCIENTIFIC PRIORITY FOR THIS PARTICULAR AREA OF RESEARCH AND PROVIDE RIGOROUS SCIENTIFIC REVIEWS AS WELL AS FOR THE CONCEPT. IT IS OUR EXPECTATION THAT WITH THE COMMITTEES BEING POPULATED WITH BOTH COMMUNITY INVESTIGATORS AND EXPERTS IN THE AREA THAT THE STUDIES THAT HELP YOU MOVE FORWARD WOULD BE ONES THAT WOULD HELP US IN OUR IMPLEMENTATION AND GIST SEMINATION FROM OUR CLINICAL TRIALS AND THAT WE CAN ACCELERATE THAT BY THE STUDIES SIMULTANEOUSLY. THE CO-CHAIRS OF A CANCER CARE DELIVERY STEERING COMMITTEE ARE PAWED GODLY FROM THE UNIVERSITY OF NORTH CAROLINA AND BRAD POLLOCK FROM THE UNIVERSITY OF CALIFORNIA DAVIS WHO IS ALSO THE P. I. FOR THE CHILDREN'S ONCOLOGY GROUP. I WON'T GO THROUGH THIS BUT THIS IS THE TEMPLATE FOR THE COMPOSITION OF THE COMMITTEE AND WE WOULD ADHERE TO IT FOR THIS PARTICULAR COMMITTEE. SO THE EARLY NEXT STEPS FOR CANCER CARE DELIVERY RESEARCH WOULD INCLUDE THE FACT THAT WE ARE SUBMITTING--I THINK THIS WEEKEND A LIST OF POTENTIAL CANDIDATES FOR THE CLINICAL TRIALS COORDINATING COMMITTEE TO BEGIN THEIR VETTING PROCESS AND TO BEGIN THE PROCESS BY IDENTIFYING THE RESEARCH PRIORITIES AND INITIATING THE GROUP THAT WOULD SERVE WITH THE STEERING COMMITTEE AND CHARACTERIZE THE HEALTHCARE ENVIRONMENT AND CAPACITIES WITHIN BOTH COMPONENTS ACROSS THE NCORPS. SO HOW DO THE COMMUNITY INVESTIGATOR RESEARCHES CONTRIBUTE TO THE NCORP? CERTAINLY THEY HAVE THE RESEARCH COMMITTEES AND OTHER COMMITTEES WITHIN IT IS RESEARCH BASIS THEY ARE REPRESENTED ON THE DISEASE AND NONDISEASE STEERING COMMITTEES. THEY ARE REPRESENTED ON 12 OF THE 16 AND 15 OF THE EXISTING TASK FORCES. THEY ARE MEMBERS OF THE TRANSLATION ADVISORY COMMITTEE, THEY ARE ASKED TO PROVIDE IN INITIATIVES THAT WERE HELD LIKE SEPTORS NINTH IN WHICH THE NCI INVOLVED CLINICAL TRIALS SYSTEM IN THE JOINT NCAB AND BSA AND THERE ARE--WE ARE PLANNING TO DEVELOP A GROUP OF LOOKERRING AT DESIGNING STUDIES THAT EVALUATE NATURAL EXPERIMENTS RELATED TO HELP POLICY CHANGES AND HOW THESE MIGHT EFFECT CLINICAL OUTCOMES. THIS WAS ALOUDED TO THE ONE AND THIS SPOKE WITH THE POLICY AND HOW IT WOULD PRACTICE THE CONONCOLOGY IN THE COMMUNITY SETTING. SO AS WE MENTIONED BEFORE, WE WORK WITH THE CLOSE PREVENTION ASK TREATMENT AND DIAGNOSIS. AND WE ALSO ARE THE SYSTEM THAT COMMUNICATES THE AUDITING, ROSTERING IS ONE THAT CONNECTS THE TWO PROGRAMS TO BE WELL INTEGRATED. ABOUT SEVEN% OF OUR COMMUNITY PRACTICES ARE PARTICIPATE NOTHING THE CENTRAL IRB THAT WERE LISTED FOR TREATMENT AND WE ARE VERY EXCITED TO ANNOUNCE TAKEN--THEY THERE WILL BE A CENTRAL IRB THAT WILL BE LAUNCHED IN JANUARY 2015 AND WILL HELP WITH CANCER AND CONTROL. SO IN CONCLUSION WE FEEL WE HAVE PREP PRESENTED THE REAL WORLD ONCOLOGY PRACTICES, WE FEEL WE'LL BEEN RESPONSIVE TO THE EXTENSIVE STAKEHOLDER INPUT, THEY NEED TO PREPARE AND SUPPORT THE SCIENTIFIC ARK GENDA HAVING MADE SOME SELF-ASSESSMENTS AND BEING RERESPONSIBLE FOR MEDIEVALS FOR EXTERNAL THROUGH PRACTICES. WE THINK THERE THAT THERE CAPACITY TO SUSTAIN OR IMPROVE CLINICAL TRIALS ACCRUALS TO ALL CONPOEMENTS OF THE NCTN. AND BECAUSE OF SOME OF THE NETWORKS AND THE ORGANIZATIONS AND SYSTEMS WE THINK WE HAVE A BROADER BASE OF INDIVIDUALS AT RISK OF CANCER TO HELP US AND BRING FURTHER PREVENTION. AND FINALLY IT IS AN OPPORTUNITY TO EVALUATE AND INFLUENCE THE CURRENT HEALTH CARE SYSTEMS UNDER THE SUCCESSFUL CONDUCT AND IMPLEMENTATION OF DECISION MEDICINE THAT'S BEEN MOVED FORWARD. THANK YOU AND I'LL HOLD QUESTIONS UNTIL AFTER THE NEXT SESSION. >> I THINK IN THE INTEREST OF TRYING TO BE EFFICIENT WITH EVERYBODY'S TIME I'M GOING TO ASK PHIL TO GO AHEAD AND GIVE LIAISONS PRESENTATION AND THEN WE'LL TRY TO ENTERTAIN A FEW QUESTIONS AS I THINK BOTH PRESENTATIONS WILL INTERSECT PRETTY NICELY. >> I'LL TRY TO BE BRIEF SINCE WE'RE NEARING LUNCH. >> IT'S BEEN AN INTERESTING YEAR FOR THOSE OF US IN THE COIP PROGRAM, OBVIOUSLY SOME OF THESE CHALLENGES WE KIND OF EXPECTED WE'VE KNOWN ABOUT THIS PROGRAM FOR SOMETIME AND AS WE BEGAN TO WRITE OURA GRANTS ALMOST ABOUT A YEAR AGO NOW, THESE WERE CERTAINLY EXPECTED AND ANSWERED. THEY ARE HOWEVER CERTAINLY THE CAPABILITY OF UNKNOWN CHALLENGES THIS, IS UP AND RUNNING NOW AND ONE WONDERED ABOUT HOW THINGS WILL APPEAR. THERE'S SOME FEELINGOT COMMUNITY OF NERVOUSNESS ABOUT WHAT WILL HAPPEN IN THE FUTURE AND THAT'S ALWAYS TO BE EXPECTED. AND OF COURSE, SOME OF THE CHALLENGES ARE VARIABLE, AS YOU SAW THE STRUCTURE OF THE NCORP, NOT ALL NCORPS ARE THE SAME. ORGANIZATIONAL STRUCTURES VARIES SO THE CHALLENGES FOR THESE VARIOUS NCORPS MAY BE DIFFERENT AND WE'VE SEEN NAIN DISCUSSIONS WITH THE OTHER PIs AROUND THE COUNTRY. SO I PUT TOGETHER A LIST OF CHALLENGES ISSUES OBVIOUSLY BIASED ACCORDING TO WHAT WE'VE SEEN IN OUR GROUP BUT ALSO FROM SHOULD SOME OF THE COMMENTS FROM THE PIs, AROUND THE COUNTRY. WE CERTAINLY DISCUSSED THE NATIONAL PLANS TO DECREASE ACCRUAL IN THIS COMMITTEE AND WE'VE HAD DECREASED EXPECTATION NUMBERS IN OUR GRANT WHICH KIND OF CONFIRMS SOME OF THAT. OT OTHER HAND IF YOU THINK ABOUT IT, THERE AREN'T MANY WAYS TO EVALUATE IN THIS CANCER CARE DELIVERY RESEARCH AND PROGRAM ISN'T YET UP AND RUNNING, SO WE'RE A LITTLE UNCLEAR AS TO WHAT THE AMOUNT OF EMPHASIZE WILL BE CERTAINLY ON ACCRUAL AND TREATMENT AND CANCER CONTROL AND PREVENTION ACCRUAL. THERE ARE FEWER TRIALS NOW APPROVED. THERE ARE FEWER WHAT I CALL A+, B TREATMENTS WHAT I CALL PATIENTS GETTING A+ TREME VERSES B, AND WE COULD PUT A HUNDRED PATIENTS ON NEGATIVE BREAST CANCER--I THINK THE SCIENCE OF PRECISION MEDICINE CLEARLY NEEDS TO BE PUSHED FORWARD BUT THIS PRESENT ACE CHALLENGE TO THE COMMUNITY SIBS SINCE THIS IS SOMETHING WE'RE NOT USED TO. TARGETED THERAPY TRIAL TAKE A LOT OF TIME TO DISCUSS PATIENTS AND THERE WILL BE A BUILT-IN DELAY ON PATIENTS WITH SECOND LINE METASTATIC DISEASE AND THE TRIAL AND WHILE THEY WAIT FOR THEIR GENETIC ANALYSIS, AND THEY SIMPLY ARE GOING TO BE RESISTANT TO THAT. YOU CAN TAUNT THE PATIENTS BUT THAT REQUIRES MORE TIME AND AS WE KNOW, PHYSICIAN TIME COMMIMENT CONTINUES TO INCREASE ON AREAS OTHER THAN CLINICAL TRIALS WITH EMR AND OTHER KINDS OF ISSUES AND OF COURSE FUNDING IS AN ISSUE WITH ACCRUAL. OUR FUNDING QUITE FRANKLY FOR CLINICAL TRIALS ACTIVITY WENT DOWN AS IT DID IN MANY OF THE NCORPS. AND SO WE HAVE TO BE LOOKING AT TRYING TO DO THIS ACCRUAL MORE EFFICIENTLY, HOW MUCH ACCRUAL, WHAT WE NEED TO DO, HOW DO I DO THAT WITH THE EXISTING FUNDING SO WE'RE RAPIDLY FUNDING LOOKING AT BUDGETS, THROUGH OUR PROGRAM AND TRYING TO CONTINUE OUR ACCRUAL. IT'S CERTAINLY A CHALLENGE. NOT THAT IT CAN BE THE BE DONE BUT I CHALLENGE. BUT ANOTHER AREA OF CHALLENGES, ARE THE NEW INITIATIVES. CANCER CARE DELIVERY RESEARCH, IS CERTAINLY SOMETHING NEW FOR US. I THINK IT'S TIMELY AND CERTAINLY NEEDED, BUT WE'RE ASKED THIS YEAR TO COME UP WITH INFRASTRUCTURE TO CONDUCT CANCER CARE DELIVERY RESEARCH AND SOME OF THE NCORPS HAVE A LITTLE EXPERIENCE COMING UP WITH IDEAS ON MATCHING WHAT THE NCIs DOING IN TERMS OF PROCESS OF NCORP, ONE OF THE THINGS I WORRY ABOUT IS HOSPITAL BUY-IN, WE HAD PRETTY GOOD BUY-IN FOR OUR GRANT AND THIS I MAY NOT COME ABOUT BUT WILL HOSPITALS LOSE THEIR COMMITMENT TO DO CANCER CARE DELIVERY RESEARCH IF THERE'S A BIG TIME ELEMENT BETWEEN WHEN THE GRANT WAS ACTIVE AND WHEN WE'VE TALKED TO THEM AND WHEN THESE TRIALS GET ACTIVATED. HOPEFULLY NOT, WE'RE GOING TO KEEP WORKING WITH THEM ALL CHALLENGES I MENTIONED, MINORITY RECRUITMENT HAS NOT BEEN A NEW CHALLENGE BUT WE SEE A NEW REINVIGNETTESERATION AND WE SEE A DISPARITIES RESEARCH CONCEPT IS RELATIVELY NEW FOR US AND WE HAVE TO SEE HOW THAT PLAYS OUT BUT THE CHALLENGE FOR US TO COME UP WITH NEW WAYS TO TRY TO IMPROVE MINE RECRUITMENT. THERE ARE CONFUSIONs AS WELL. OUR GRANT WAS DINGED BECAUSE WE DIDN'T COME UP WITH HOW WE GED RETIRED OF BARRIERS TO CLINICAL TRIAL ACCESS EVEN THOUGH OUR NCORP DOESN'T PROVIDE CARE TO CLINE DALE PATIENTS SO IT'S A CHALLENGE TO WORK WITH HOSPITALS TO TRY TO DO THIS. OTHER CHALLENGES I DIDN'T MENTION, THE ACADEMIC COMMUNITY RELATIONSHIPS, AGAIN VARY BY NCORPS WE HAVE A GOOD RELATIONSHIP, AT LEAST GETTING BETTER IN OUR COMMUNITY BUT OTHER NCORPS MAY HAVE--MAY SEE THIS AS MORE OF A CHALLENGE. MANY RESEARCHER ARE NOW AMING UP WITH ACCRUAL MINIMUMS WELL THAT'S FINE BUT WHEN YOU HAVE DECREASED ACCRUAL AND YOU PARTITION YOUR ACCRUAL OVER WHEN YOU MAY BELONG TO THERE MAY BE AFFILIATION ADJUSTMENTS THAT COME ABOUT. I VICTORY SEEN THIS YET IN TALKING TO THE PIs BUT THIS CERTAINLY IS A POSSIBLE CHALLENGE FOR THE FUTURE AND WE ASKED OUR QUESTION WHAT DO WE DO WITH SMALLER EN--STRATEGIES TYPINGSS THAT PUT ONLY A FEW PATIENTS ON TRIAL IF OUR FUND SUGGEST DECREASED, HOW DO I KIND OF CENTRALIZE THINGS THAT OUR SMALLER INSTITUTIONS CAN STILL PARTICIPATE? BECAUSE IF I ELIMINATE SMALLER INSTITUTIONS ISN'T THAT GETTING RID OF THEIR ACCESS TO CLINICAL TRIALS AND THE PATIENT'S IN OUR RURAL AREAS, ESPECIALLY IN THE APPALACHIAN REGIONS WE SERVE IN OHIO. I DO LIKE THE IDEA THAT RESEARCH GROUPS ARE REQUESTING MORE PARTICIPATION AMONG COMMUNITY PHYSICIANS THAT REQUIRES SOME EDUCATION OF OUR COMMUNITY PHYSICIANS, THERE THEY'RE USED TO PUTTING THEM ON TRIAL, HOW DO I GET THEM INVIGORATED TO GET ON PARCOMMITTEES AND PARTICIPATE ON THEM IT'S A CHALLENGE. WE'RE HAPPY THERE PROBABLY WILL BE PROTOCOL STANDARDIZATION ACROSS THE GROUPS ANDENTIOUS SPECIALLY AUDIT STANDARDIZATION. I'M TIRED OF BEING DINGED FOR ONE THING ON BY ONE GROUP ON THE SAME THING THAT I'M NOT DINGED FOR BY ANOTHER GROUP IN THE TRIAL. SO IF AUTOMATICKIZATION COMES AROUND ALL OF US WILL BE HAPPY. AND FINALLY, IRBISSUES, FOR MOST OF US WE'VE BEEN IN THERE AND IT'S ENTIRELY NEW FOR SOME OF THE NCORP PIs AND IT WILL BE A CHALLENGE. WE'VE HAD TO DO SITE CODES AND DO PAPERWORK IN THE LAST MONTH OR TWO AND THAT'S BEEN A BIG CHALLENGE ESPECIALLY WHEN WE TRY TO REGISTER PATIENTS AND FIND OUT THAT THEY DIDN'T HAVE THEM. AND WE COULDN'T EVEN REGISTER THE PATIENTS WE HAD TO FIGHT WITH THAT. A LOT OF THAT'S BEEN KIND OF WORKED OUT BUT IT CERTAINLY WAS A CHALLENGE. OUR TESTS ARE COMPLEX AND THERE MAY BE PROCEDURE FIST THAT ARE AND THERE MAY BE DELAYS IN OUR IMREBUSKERMENT SO IN SUMMARY THERE'S VELOCITY SURROUNDING THE NCORP PROGRAM FOR MANY OF US. BUT I'M BEGINNING TO SEE THROUGH SOME OF THAT, MAYBE SEE SOME OF THE STARS BEHIND IT AND MY HOPE IS THAT SOME OF THE VELOCITY WILL CONTINUE TO DISSIPATE HOPEFULLY FASTER THAN IT WILL FOR THE ROSETTE NEBULA HERE IN THE FUTURE. THANK YOU. >> THANK YOU. >> VERY NICE. SO THERE IS GOOD NEWS, THE EUROPEAN SPACE AGENCY HAS BEEN ABLE TO LAND ITSELF STROBE ON TO A COMET FOR THE FIRST TIME SO I THINK WE'LL--WE'RE ON THE RIGHT TRACK. SO WE HAVE--WE HAVE MAYBE A FEW MINUTES FOR QUESTIONS? WE WILL--I THINK WE CAN KITCHEN--WE'RE A BIT BEHIND BUT I THINK WE CAN CATCH UP IN THE AFTERNOON WITHOUT TOO MUCH DIFFICULT SO IF THERE ARE QUESTIONS FOR EITHER PHIL OR--YES, CHRIS? >> SO PHIL, I HAD A QUESTION FOR YOU, IN THE COMMUNITY PRACTICE SETTINGS THAT HAVE THE NCORP PROGRAMS HOW MUCH COMPETITION IS THERE FOR INDUSTRY STUDY? SO AS AN INVESTIGATOR, I THOUGHT ACADEMIC CENTERS BUT THERE'S SECONDARY GAIN TO DO INVESTIGATOR INITIATED TRIALS OR GROUP TRIALS IN THE ACADEMIC SETTING THAT PUSHED US. >IT VARIES ACROSS NCORPS. SOME ARE USING INVESTIGATION OR PHARMACEUTICAL TRIALS TO TRY TO BRIDGE THAT FUNDING GAP. WHETHER IT JUST HAPPENED, I DOUBT IT, ACTUALLY, IN OUR INDUSTRY WE'VE NOT WANTED TO DO COMMUNITY TRIALS WHERE WE'RE PRETTY DEDICATED TO THE NCI THRILLS BUT SOME OF OUR PRACTICES ARE HEAVILY INVOLVED. AND THAT DOESN'T TAKE AWAY ACCRUAL IN THOSE PRACTICES FROM OUR NCORP. SO IT DOES HAVE AN EFFECT. D. SO IN THE MODEL FOR THE SCREENING AND SURVEILLANCE COMPONENTS IN NCORP, IN THINKING ABOUT IMAGING COMPONENTS IS THERE AN OPPORTUNITY TO WORK WITH PAYERS, IS IN SETTING SOME OF THOSE MEASURES THAT YOU'RE GOING TO BESTING IN SCREENING AND SURVEILLANCE MAY GET PRICEY AND ODES OF THE SCOPE IS THERE OPPORTUNITIES WHERE OPPORTUNITY PARTNERS CAN BRING IN PAYORS OR DESIGN JOINT TRIALS AS IS HAPPENED IN SCREENING AREAS? >> YES THERE ARE AND THERE ARE DISCUSSION ONGOING NOW FOR IDEAS AND THE TRIALS AND PAYORS ARE VERY MUCH INVOLVED IN IT, VERY MUCH. >> OKAY, SO WE'RE RUNNING A LITTLE BEHIND. SO WHY DON'T WE PLAN TO RESUME AT ABOUT 1:10. LET'S MAKE IT 1:15 THAT WILL GIVE US A LITTLE OVER 45 MINUTES FOR LUNCH. AND AS I SAY, I THINK WE CAN CATCH UP IN THE AFTERNOON WITHOUT TOO MUCH DIFFICULTY AND WE'LL RECONVENE AT 1:15 AND I UNDERSTAND THAT FOR THOSE WHO ORDERED THEM, THEY'RE OUTSIDE CONFERENCE ROOM NIGHT. JUST RIGHT OUTSIDE. >> OKAY, WE'LL GET STARTED. TRY TO CATCH UP SOME TIME OVER THE NEXT COUPLE PRESENTATIONS. SO ONE OF THE THINGS THAT IN TERMS OF DOING THE AGENDA SETTING FOR THE MEETINGS, WE WANTED TO HAVE ONE MORE SCIENCE ORIENTED PRESENTATION, AS YOU HEARD THIS MORNING WE WILL PROBABLY TRY TO GET DR. MCCORMICK OR ONE OF THE MEMBERS, HIS GROUP WORKING ON THE KRASE MODEL PROJECT TO GIVE US AN UPDATE OF THE STATUS BECAUSE I KNOW THEY ARE CONTINUING TO DO A LOT OF WORK IN THAT AREA AND IT RELATES OBVIOUSLY TO A NUMBER OF DISEASES INCLUDING PANCREATIC CANCER WHERE WE HAVE A VESTED INTEREST WITH OUR WORKING GROUP TO OVERSEE PROGRESS IN THAT AREA. SO THE NEXT PRESENTATION FROM SUSAN HOLBECK AND JERRY COLLINS AND STIMULATED BY WORK WE HEARD ABOUT A COUPLE MEETINGS AGO, SORT OF A COMBINATTORRIAL APPROACH TO PRECLINICAL DRUG DEVELOPMENT THAT I THOUGHT WOULD BE INTERESTING FOR US TO HEAR MORE DETAILS B. SO JERRY'S HERE TO ADDRESS QUESTIONS. I THINK SUSAN'S GOING TO ALY GIVE THE PRESENTATION. >> OKAY, WELL, THANKS FOR INVITING ME TO COME AND TELL YOU ABOUT THE WORK THAT'S BEEN ONGOING AND THE DEVELOPMENT ON THERAPEUTICS PROGRAM WHICH IS PART OF THE DIVISION OF CANCER TREATMENT AND DIAGNOSIS HERE AT NCI. I THINK EVERYBODY UNDERSTANDS THE REASON TAKEN--THEY WE NEED TO DISCOVER NEW COMBIN AGESS SINGLE AGENTS ARE RARELY CURATIVE AND IF SOMEBODY DOES RESPOND TO ONE OF THE TARGETED AGENTS IT'S ALMOST CERTAIN THEY WILL EVENTUALLY RELAPSE. SO THERE HAVE BEEN A LOT OF DIFFERENT STRATEGIES THAT HAVE BEEN PUT FORWARD TO COME UP WITH COMBIN ANTICIPATIONS THAT MIGHT BE TESTED--COMBINATIONS THAT HAVE BEEN TESTED. A LOT OF PEOPLE HAVE BEEN UNDERSTANDING PATHWAYS AND UNDERSTANDING RATIONAL COMBINATIONS BASED ON PATHWAYS THAT ARE DRIVING THOSE TUMORS WITH MIXED SUCCESS AND THEN THERE ARE MORE COMPREHENSIVE APPROACHES TO COMBINATION DISCOVERIES INCLUDING SiRNA SCREENS OR IMPERRENT DRUG SCREENS WHICH IS WHAT I WILL ADDRESS TODAY. SO I WILL TELL YOU ABOUT TWO PARALLEL ACTIVITIES THAT ARE WE'VE HAD UNDERWAY AT NCI, THE FIRST OF THESE IS A COMPREHENSIVE SCREEN OF MOST OF THE APPROVED FDA APPROVED SMALL COLKIEWL CANCER DRUGS. SO WE DID CALL THIS NCI ALMONITOR ACWITH THE DECODING OF THE NAME. WE TESTED OVER A HUNDRED SMALL MOLECULE ONCOLOGY DRUGS AND TESTED ALL POSSIBLE PARALYZED COMBINATIONS OF THESE WHICH IS ABOUT 5000 DRUG PAIRS AND WE TESTED EACH OF THESE DRUG PAIRS. AND WE TESTED THESE IN THE PANELS, AND IT WAS OVER 300,000 EXPERIMENTS AND IT WAS RUN AT TWO CONTRACTOR LOCATIONS AT A COST OF JUST OVER FOUR MILLION DOLLARS, ONE MILLION PER WELL. IT MAKES A DIG DIFFERENCE. SO THIS SLIDE ADDRESSING IS SHES, SO THIS IS LOOKING TO SEE WHAT--WHICH OF THE APPROVED DRUGS HAS BEEN TEST WIDE OTHER ONES AND IS ACTUALLY VERY DIFFICULT DATABASE TO MINE BECAUSE IT'S A WONDERFUL, WONDERFUL RESOURCE BUT IT'S NOT STANDARDIZATION OR FEEL OF THINGS ARE IN BUT I MIND OUT CO OCCURRENCE OF APPROVED DRUG NAMES IN THE SAME CLINICAL TRIAL. SO IF ANYTHING IT'S AN OVERESTIMATE OF WHAT HAS BEEN TESTED AND FOUND ONLY ABOUT A QUARTER OF APPROVED DRUGS WERE FOUND IN THE SAME CLINICAL TRIAL SO THAT MEANS THERE'S A LARGE NUMBER OF PROBABLE PAIRS OF APPROVED DRUGS THAT HAVE NO CLINICAL EXPERIENCE. SO ABOUT 3700 OF THESE. SO THEN THE QUESTION IS, CAN WE DISCOVER AMONG THESE, THESE ARE THE WHITE SPACES IN THIS GRAPH, THE DOTS INDICATE CASES WHERE THE TWO DRUGS WERE FOUND TOGETHER IN THE SAME CLINICAL TRIAL. SO IN THESE WHITE SPACES CAN WE DISCOVER BENEFICIAL PAIRS WE MIGHT PUT INTO CLINICAL TRIALS. SECOND QUESTION IS WHY THE NCI SECTIONAL ANALYSIS? THIS IS HAS BEEN A WORK HORSE IN THE DEVELOPMENTAL THERAPEUTICS PROGRAM FOR A LONG TIME AND AS A CONSEQUENCE WE HAVE A LARGE DATABASE OF DRUG ACTIONS. WE HAVE EXTENSIVE CHARACTERIZATION OF THE CELL LINES OF MOLECULAR LEVEL. BASICALLY ANYTHING YOU CAN THINK OF HAS BEEN TESTED. MOST OF THE CELL LINES IN THE PANEL WILL GLOW AS XENOGRAFTS AND AS FOLLOW ON STUDIES AND JUST THIS PAST YEAR, THEY PUBLISHED DATA FROM XENOGRAFTS AT DIFFERENT CALCULATIONS, SO WE HAVE THE POSSIBILITY OF DOING PREDICTIVE DISCOVERY OF BIOMARKERS THAT MIGHT INFLUENCE SENSITIVITY TO A COMBINATION. THIS JUST LISTS THE TYPES OF CHARACTERIZATION THAT WE HAVE ON THE NCI 60 AND YOU CAN SEE THAT IT REALLY COVERS THE GAMUT FROM SEQUENCING, KNOWING ALL OF THE MUTATIONS THAT ARE PRESENT IN THE CELL LINES. WE HAVE LARGE SCALE PROTEIN EXPRESSIONS, DATA AND ALSO THINGS THAT HAVE BEEN DONE ONE AT A TIME IN SMALL LABORATORIES. SO ALL THIS DATA IS AVAILABLE TO US TO TRY TO UNDERSTAND THE CONTEXT IN WHICH THE COMBINATION WORKS OR DOESN'T WORK. SO I TOLD YOU WE DID 300,000 EXPERIMENTS OF 5000 DRUGS AND 60 CELL LINES. HERE'S WHAT THE DATA LOOKS LIKE FOR ONE OF THE COMBINATIONS. SO ONE OF THESE 300,000. IT'S A COMPLICATED SLIDE SO NEXT ONE I'VE BROKEN IT DOWN JUST PART OF IT. GO THROUGH IT. THE RED LINE, SO WE TESTED THREE CONCENTRATIONS OF EACH DRUG, AND OF COURSE SINGLE AGENTS. THE RED LINE IS THE GROWTH INHIBITION WE SEE FROM ONE OF THE SINGLE AGENTS BY ITSELF. OT Y-AXIS HERE YOU CAN SEE THAT--ON THE Y-AXIS HERE CAN YOU SEE THAT OUR UNITS GO FROM A HUNDRED PERCENT, NO GROWTH INHIBITION, HUNDRED PERCENT OF THE GROWTH TO UNTREATED CELLS TO ZERO WHICH IS THE STARTING NUMBER OF CELL LINES AND WE DO A TIME ZERO MEASUREMENT. SO WE WE'RE ABLE TO TELELESS THAN ZERO, SO THE BOTTOM IS MINUS A HUNDRED. THE X-AXIS IS CONCENTRATION OF AGENT ONE. SO AGENT ONE BY ITSELF IS THE RED LINE. THE DID SHE LINE IS ONE OF THE CONCENTRATIONS OF HNTWO BY ITSELF, SO WHAT WE'RE LOOKING FOR ARE CASES WHERE THE COMBINATION IS BETTER THAN BOTH OF THE SINGLE AGENTS. AND THAT IS TRUE FOR THIS ONE. THE BLUE SOLID LINE IS THE COMBINATION AT EACH OF THESE CONCENTRATIONS. WE CAN CALCULATE WHAT WE WOULD EXPECT TO SEE IF THE COMBINATION WERE ADDED TOO AND THAT'S INDICATED BY THE STARS, SO THEN THE GREEN ARROWS SHOW WHAT DID YOU SAY WE HAD SEEN IN EXCESS OF WHAT WOULD BE EXPECTED SO WE SUM THIS UP ACROSS ALL THREE DOSES FOR BOTH AGENTS, TOTAL OF NINE POINTS, ADD UP THOSE GREEN ARROWS AND COME UP WITH A COMBINATION SCORE. THAT ALLOWS US TO LOOK AT THE DATA AS A WHOLE AND SO, HERE'S A HEAT MAP BASED ON THAT COMBINATION SCORE, CELL LINES GO ACROSS THE X-AXIS, DRUG PAIRSOT Y-AXIS AND THE HEAT MAP MEANS THAT THE COMBINATION WAS BETTER THAN EXPECTED IF THEY WEREADATIVE, BLUE MEANS WORSE THAN INSPECT FEDERAL THEY WERE ADDITIVE. AND WHAT YOU CAN SEE FROM THIS IS THAT AT THE BOTTOM THERE ARE SOME DRUG PAIRS THAT GAVE HIGH SCORES IN JUST ABOUT EVERY CELL LINE. IN THE MIDDLE THERE ARE SOME DRUG PAIRS THAT GAVE LOW SCORES AND JUST ABOUT EVERY CELL LINE. AND THEN SCATTERED THROUGHOUT ARE SOME DRUG PAIRS THAT DO WELL AND ONE CELL LINE AND NOT IN OTHER CELL LINE. THOSE ARE THE CASES WHERE WE COULD HAVE SOME OPPORTUNITY TO DO A MOLECULAR UNDERSTANDING OF WHAT MIGHT BE THE BASIS FOR THAT; SO I WANT TO TAKE YOU THROUGH A COUPLE EXAMPLES THAT HAVE COME OUT OF THE SCREEN, THE FIRST OF THESE IS BBOTEZOMIB, PLUS CLOFARABINE, YOU CAN SEE THERE WERE A NUMBER OF GOOD SCORE LINES THAT GAVE A GOOD SCORE. WE TESTED FIVE OF THESE IN XENOGRAFTS, AND THREE WERE ACTIVE AND TWO WERE NOT. SO THE BOTTOM SHOWS XENOGRAFT ACTIVITY FOR ONE OF THE CELL LINES THAT WAS RESPONSIVE, AND THE LINE HCT-1 116. THE BLACK LINE IN THE LOWEST GRAFT IS THE CONTROL MICE, OR MICE THAT WERE UNTREATED. THE TWO DIFFERNT CONCENTRATIONS THAT WE USED WERE INACTIVE INDICATED BY THE B. CLOFARABINE HAD ACTIVITY BUT THE COMBINATION WAS EVEN BETTER SO WE HAD SEVERAL DIFFERENT COMBINATION ARMS CAN AND IN FACT WE SEE REGRESSIONS WITH THE COMBINATION AND THE PERIOD OF TREATMENT AS INDICATED BY THE BAR AT THE BOTTOM. SO THIS IS A COMBINATION WE'VE ADVANCED TO A COMBINATION OF TRIALS AND SHUMANI IS OVER SEEING THIS AT THE CLINICAL CENTER. ONE PATIENT HAS BEEN TREATED SO FAR. SO, EARLY DAYS. BUT ONE SUCCESSFUL TRANSLATION TO THE CLINICS. A SECOND EXAMPLE, IMENT TO SHARE WITH YOU IS ONE THAT IS STILL WORKING TINGS WAY THROUGH THE APROFFAL PROCESS AND THIS IS A DRUG PAIR THAT IS--HAS GOOD ACTIVITY IN TRIPLE NEGATIVE BREAST CANCER MODELS. SO IN OUR NCI 360 PANEL WE HAVE SIX BREAST CANCER LINES, FOUR OF THOSE ARE TRIPLE NEGATIVE AND HERE I'VE DONE LIKE WATER FALL PLOT OF THE HEAT MAP SO WITH THE MOST RESPONSIVE MODELS, A ALSO HAVE THE BEST BENEFIT FROM THE COMBINATION OF TOP IN RED AND THOSE THAT DON'T BENEFIT IN BLUE NEAR THE BOTTOM SO THE TRIPLE NEGATIVE ARE ALL AT TOP. THE TWO--THE TWO NONTRIPLE NEGATIVE BREAST CANCER MODELS ARE DOWN NEAR THE BOTTOM SO BOTH OF THOSE DID NOT BENEFIT FROM THIS COMBINATION. SO, MDMD468 TRIPLE NEGATIVE BREAST CANCER MODEL WE TESTED WITH IN XENOGRAFTS AND THAT DATA IS SHOWN ON THE PANEL IN THE RIGHT AND THIS IS DATA FROM MELINDA HOLLINGSHEAD. SO WE SEE THE NO DRUG CONTROL IN BLACK, DRUG A, WAS INSERT AS IF IT HAD BEEN GIVEN THE DRUG B, PRETTY ACTIVE, STASIS FROM A PERIOD OF TIME BUT THEN THE TUMOR BEGINS TO GROW BUT WITH THE COMBINATION, GET COMPLETE REGRESSIONS. AND IN FACT, WE SEE TUMOR FREE ANIMALS OUT TO 130 DAYS WHICH IS THE LATEST POINT THAT WAS MEASURED. VERY IMPRESSIVE. ALMOST NEVER SEE ANYTHING THAT LOOKS LIKE THIS. SO WE LOOKED AT A COUPLE OTHER MODELS OF THE FOUR TRIPLE NEGATIVE MODELS WE HAVE IN THE NCI 60, ONLY TWO WILL GROW AS XENOGRAFTS SO WE TESTED THE BOTTOM ONE WHICH WAS THE ARROW WHICH HAD THE MDA 41 AND THAT HAD A MORE MODEST SCORE AND THAT XENOGRAFT THE COMBO ARTICLES WERE BETTER AS AGENTS AND THEN WE ALSO TESTED TRIPLE NEGATIVE MODELS, THAT'S NOT PART OF THE MCI 60, SO ONE THAT WE HAD NO CELL LINE DATA TO KNOW WHETHER OR NOT IT WOULD RESPOND AND THAT ONE AGAIN, THE COMBO ARMS WERE BETTER THAN SINGLE AGENTS. SO IT LOOKS IMPRESSIVE, AT LEAST IN THE MODELS WE'VE USED SO THERE'S ONE THAT'S WORKING THAT WAY THROUGH THE APPROVAL PROCESS. ALL OF THIS DATA WILL BE PUBLIC, WE'RE WORKING ON THE FINAL STAGES OF GETTING A MANUSCRIPT OUT, BUT DEVELOPED A WEB SITE THAT WILL BE DEPLOYED AS SOON AS THAT IS ACCEPTED AND MAYBE A FEW SCREEN SHOTS OF WHAT THAT WILL LOOK LIKE BECAUSE WE WANT TO BREAK THIS BROADLY USEFUL TO CLINICIANS AND TO RESEARCHERS AND WE THINK THAT THERE MIGHT BE A LOT OF DIFFERENT WAYS THAT PEOPLE MIGHT WANT TO ACCESS IT, SO WE'VE DEVELOPED DIFFERENT DOORS TO GET IN AND POKE AROUND IN THE DATA. THERE ARE WAYS TO WALK YOU THROUGH THAT AND I WILL WALK YOU 32 THE EXAMPLE, BUT SOMEBODY MIGHT SAY, I WANT TO SEE WHAT THESE TWO INDIVIDUAL DRUGS LOOK LIKE, I DON'T CARE ABOUT THE REST OF THEM. THEY WILL BE ABLE TO DO THAT IF SOMEBODY HAS A PARTICULAR DRUG OF INTEREST, THEY CAN FOCUS IN ON JUST THE COMBINATIONS THAT DRUG THAT IS USED WITH THE OTHER ONES. SO I WILL WALK YOU THROUGH THE ANALYZING WITH THE HEAT MAP. SO THIS IS AN OVERVIEW OF THE WHOLE SCREEN. HERE WE CAN CHOOSE WHAT WE USE THE HEAT MAP TO DISPLAY. HERE I CHOSEN TO LOOK AT NUMBER OF CELL LINES THAT MET AN EFFICACY GOAL AND IN THIS CASE, WE HAD A SCORE TAKEN--THEY WE DETERMINED TO BE USEFUL AND SO, THE CELL LINES THAT ARE RED OR GRAY HAVE MORE CELL LINES, COMBINATIONS THAT HAVE--RED OR GRAY ARE THOSE THAT ARE MORE CELL LINES RESPONDED TO THE COMBINATIONS. THOSE IN BLUE HAD NO CELL LINES MUTING OUR GOAL EFFICACY. SO I POINTED OUT THIS WITH THE ARROW SO IF WE WOULD CLICK ON THE CELL, WE WOULD GET A BAR GRAPH SHOWING US THE DATA FOR THAT COMBINATION AND THEN IF WE CLICK ON THE BAR, WE WILL GET THE DOSE RESPONSE CURVES. SO IT'S REALLY EASY FOR PEOPLE TO DRILL DOWN AND GET TO THE DAILY BASIS THEA--DATA THAT THEY WANT. AND WE WILL MAKE THE DATA AVAILABLE FOR PEOPLE BECAUSE A LOT OF PEOPLE HAVE THEIR OWN COMBINATION OF WAYS OF LOOKING AT THE DATA AND THAT WILL ALLOW THEM TO MANIPULATE THE DATA AS THEY WISH. SO THE SECOND SCREEN I WILL TELL YOU ABOUT IS A COMBINATION SCREEN THAT WE'VE HAD GOING ON FOR ABOUT FIVE YEARS OR SO TO LOOK AT INVESTIGATIONAL AGENTS AND THESE COULD BE, FOR EXAMPLE, AGENTS ENTERING THE CTEP'S PORTFOLIO OR A MECHANISM OF INTEREST, SO THE DESIGN OF THIS IS DIFFERENT THAN WHEY DESCRIBED FOR THE NCI ALMANAC SCREEN SO WE CAME UP WITH CALLING A COMBO SET OF DRUGS, 70 DRUGS AGAINST WHICH EVERY TEST AGENT WILL BE SCREENED AND THEN TEST AGENTS WERE NOMINATED AGAIN BASED ON INTEREST TO CTEP AND TO OUR PROGRAM AND EACH OF THESE WERE THEN TESTED IN JUST THREE CELL LINES. SO THIS SCREEN TESTED THREE CELL LINES BUT IF IT WARRANTED WE WOULD ADD AN ADDITIONAL CELL LINE OR TWO TO ACCOMMODATE THE MEASURES THAT WE EXPECT TO BE RESPONSIVE. SO WE'VE DONE A TOTAL OF 27,000 COMBINATION ASSAYS IN THIS TEST. WE'VE DONE A SCORE FOR WHICH I CAMCULATED SIMILARLY FOR WHAT I DESCRIBED BEFORE AND WE CAN SEE FEATURES HERE SO THE TEST AGENTS AND CELL LINES ARE ALONG THE BOTTOM AND THE THESE ARE THAT DRUGS ARE ALONG THE TOP AND YOU CAN SEE THERE IS CLUSTERING OF ACTIVITY, THERE'S A SET OF--I WONDER IF I CAN DO THE HIGHLIGHT WITH THIS. NO? YEAH. HERE WE SEE CLUSTERS AND THESE ARE TWO IN THE COMBO SET. SO I THINK THAT RAPPA MYOSIN AND ANOTHER ONE WERE TOGETHER RIGHT ABOUT HERE SO WE CAN SEE A CLUSTERING OF MECHANISM AND I WILL TAKE YOU THROUGH A COUPLE OF EXAMPLES THAT WE HAVE FOLLOWED UP ON FROM THIS SCREEN. SO THE TWO EXAMPLES, ONE OF THEM SHOWS THAT TEST AGENTS THAT HAVE THE SAME MECHANISM CAN GIVE SIMILAR PATTERNS OF ACTIVITY AND THE SECOND EXAMPLE I'M GOING TO SHOW SURVEYS A BIT OF A SHAGY DOG STORY WHERE WE MAY HAVE DISCOVERED A NEW MECHANISM FOR AN INVESTIGATIONAL AGENT. SO HERE'S AN EXAMPLE OF TWO DRUGS HAVE THE SAME TARGET. AND THESE ARE THE RESULTS IN EACH OF THE THREE CELL LINES FOR AGENT ONEOT LEFT, AGENT TWOOT RIGHT AND THE AGENTS ARE GED ACCORDING TO MECHANISM. SO WE CAN SEE SIMILARITIES AND DIFFERENCES. WE CHOSE MORE DRUGS IN THE NCI TESTING WITH COMBINATIONS WITH BOTH OF THESE DRUGS. SO HERE ARE THE RESULTS WITH DRUG ONE AND DRUG TWO. BOTH OF THESE GAVE RED SIGNAL THAT, IS THEY HAD BENEFICIAL COMBO SCORES WITH BOTH OF THESE DRUGS AND WHEN WE PUT THEM IN THE NCI SECTIONAL ANALYSIS, CAN YOU SEE THERE'S A SIMILARITY WHEN DRUG ONE IS TESTED WITH AGENT ONE OR TWO AND LIKEWISE THERE'S SIMILARITY WITH THE TESTIG OF DRUG TWO BUT THERE ARE DIFFERENCES BETWEEN THEM AND THERE ARE FINGERPRINTS OF ACTIVITY. WE ALSO TESTED DRUG THREE AND FOUR WHICH WERE ONLY BENEFIC IN ONE OF THE AGENTS OF TWO, THESE LOOK SIMILAR BUT NOT AS WELL AS THE OTHER ONE. AND COMBINING THESE TOGETHER IS WHAT YOU CAN GET FINGERPRINTS AND YOU MIGHT WANT TO THINK ABOUT USING THIS SORT OF DA WHERE YOU COULD SAY, LET'S SAY THAT YOU HAD A TUMOR WITH THIS CHARACTERISTIC OR YOU WOULDN'T WANT TO PUT THAT PATIENT ON THIS DRUG BUT MAYBE THIS COMBINATION MIGHT BE A BETTER CHOICE AND IF YOU HAD A TUMOR WITH THESE CHARACTERISTICS WITH THIS CELL LINE YOU MIGHT WANT TO GIVE THIS PAIR OF DRUGS RATHER THAN THIS PAIR OF DRUGS JUST AS AN EXAMPLE OF THING YOU MIGHT WANT TO DEVELOP FURTHER DATA ON. SO THE SECOND STORY IS A BIT OF A SHAGY DOG, SO IN LOOKING AT ACTIVITY, WE SAW THAT TWO AGENTS THAT WE EXPECT TO DO DNA DAMAGE HAD SIMILAR PATTERNS OF ACTIVITY AND THAT'S THE TWO ON THE LEFT BUT THERE'S A 30 COMPOUND THAT SHOULD HIT A COMPLETELY DIFFERENT TARGET THAT AND AND WHAT IT COMBINES WELL WITH. SO WE DID ANOTHER EXPERIMENT TO TAKE THIS DRUG THIS IS AN ALCOLLATING AGENT AND RUN IT WITH EACH OF THESE TWO DRUGS. SO ONE THAT'S EXPECTED SENSITIZE THE DAMAGE AND THEN THE ONE THAT'S DIFFERENT MECHANISM AND THESE PATTERNS MAKE FINGERPRINTS THAT LOOK IDENTICAL FOR THESE TWO COMPOUNDS. THEN THE FINAL NAIL IN THE COFFIN IF YOU WILL IS THAT WE TEST TWOD OTHER AGENTS THAT HAVE A MECHANISM SIMILAR TO THAT REPORTED FOR THIS DRUG AND TESTED THEM WITH THE SAME ALCOLLATING AGENT AND THOSE FINGERPRINTS LOOK REASONABLY SIMILAR TO ONE ANOTHER BUT VERY DIFFERENT THAN THESE. SO WE ARE DOG ADDITIONAL EXPERIMENTS TO TRY AND CONFIRM THAT THE MECHANISM OF THIS COMPOUND IS DIFFERENT THAN WHAT WAS REPORTED. SO IN SUMMARY I'VE TOLD YOU ABOUT TWO DRUG SCREENS THAT WERE SUPPORTED HERE AT DTP. THE FIRST OF THESE NCI ALMANAC TESTED ABOUT 5000 DRUG PAIRS, ALL FDAAPPROVEED DRUGS AND NCI PANEL AND WERE UNDER COMBENATIONS OF CLINICAL TRIALS AND SECOND ONE WE HOPE TO BUT OUT OF THOSE 5000 DRUG PAIRS THERE ARE MORE OPPORTUNITIES AND MOREDATA THAN WE CAN FOLLOW UP ON AND A SECOND SCREEN WAS COMBINATION TESTING OF INVESTIGATIONAL DRUGS AND AGAIN IT'S A LOT OF VERY INTERESTING DATA IN THERE AND THERE'S A LOT OF TO PENTINE REGIMENNIAL MECHANISMS TO FOLLOW UP ON. >> SO THIS OBVIOUSLY HAD A LOT OF MOVING PARTS WHICH MEANS A LOT OF PEOPLE INVOLVED IN IT. SO JIM DOROSHOW, AND JERRY COLLINS WERE SUPPORTIVE IN THESE EFFORTS. A LOT OF FOLKS AT NCI WAS HERE WERE INVOLVED. WE NEEDED STATISTICIANS, WE NEEDED CONTRACT MANAGEMENT, WE NEEDED DATA ANALYSIS, I.T. SUPPORT AND THE NCI ALMANAC WAS RUN AT MOSTLY TWO CONTRACT LOCATIONS AND ALSO FROM THE UNIVERSITY OF PITTSBURGH AND I THANK YOU FOR YOUR ATTENTION. >> THANK YOU VERY MUCH SO PRESENTATION IS OPEN FOR QUESTIONS. I HAVE TWO QUICK ONES. ONE IS BEFORE, YOU KNOW FOR THE FIRST EXAMPLE THAT HAS GONE INTO THE PHASE ONE CLINICAL TRIAL WAS THERE ANY THOUGHT TO GIVING ADDITIONAL VALIDATION OF YOU KNOW SORT OF NEXT GENERATION STUDIES USING SORT OF PATIENT, YOU KNOW CELL LINES FROM PATIENT DERIVED XENOGRAFTS BUT VALIDATING THE COMBINATION MORE BROADLY BEFORE TAKING IT INTO THE CLINIC. >> SO YOU'RE AWARE THAT THERE ARE PATIENT DERIVED MODELS THAT ARE BEING DEVELOPED IN FREDERICK AND THOSE HAVE BEEN FAIRLY RECENT AND AND THE IDEA WAS TO GET SOMETHING OUT AS SOON AS POSSIBLE. WE HAVE GOING ON IN PARALLEL SOME PHARMACODYNAMIC MARKERS THAT WE THINK MIGHT BE INTERESTING TO FOLLOW UP ON ON PATIENTS. >> JIM DID YOU WANT TO COMMENT ON PATIENT-DERIVED MODELS? >> OF COURSE WE'RE INTERESTED IN PDF MODELS BUT THE DATA THAT EXISTS IN TERMS OF PREDICTION OF ROUTINE PHENOGRAPH, THERE'S DECADES WORTH OF DATA FROM THE DEVELOPMENTAL THERAPEUTICS PROGRAM AND INDICATES CLEARLY THAT IF HAVE YOU THREE DIFFERENT MODELS THAT HAVE SIGNIFICANT ACTIVITY, IT'S LIKELY THAT YOU ARE GOING TO SEE SOMETHING IN THE PHASE TWO SETTING IN PATIENTS. AND THAT'S REALLY THE REASON THAT WE WENT FORWARD. >> I GUESS MY OTHER QUESTION IS, BY USING THE NCI 60S CELL LINES YOU ALTS HAVE A LOT OF MOLECULAR DATA ON THOSE CELL LINES IS IT POSSIBLE TO IDENTIFY A MOLECULAR SORT OF FINGERPRINT FOR THE TYPE OF COMBINATION TESTING ONCE YOU GET THE KIND THAT YOU THINK IT CAN BE ADMINISTERED SAFELY? >> YEAH, AND THAT'S SOMETHING THAT WE HAVE UTILIZED FOR THE SO WE DID CELL LINES INVITRO AND THEN WHEN WE PUT THOSE FIVE MODELS, INTO XENOGRAFTS, THREE OF THEM WERE ACTIVE AND TWO WERE NOT, SO NOW WE'RE LOOKING AT WHAT CHANGES, IN THE XENOGRAFTS AND DISCOVER GENES THAT ARE SIMILAR FOR ALL FIVE CELL LINES AND TISSUE CULTURE AND DIVERGE FOR THE RESPONSIVE AND NONRESPONSIVE AND THAT'S VERY RECENT DATA AND THAT'S SHOULD GO THAT OUR PHARMACODYNAMICS GROUP IS FOLLOWING UP ON BUT WE HAVE INTERESTING MARKERS FROM THAT. >> OTHER QUESTIONS. >> , I WANTED TO FOLLOW ON THAT POINT ABOUT THE 40% OF THE XENOGRAFT RESULTS THAT DIDN'T RECAPITULATE THE RESULTS, I ASSUME YOU USE THE DRUG CONCENTRATIONS AND EVERYTHING, TOO? >> NO, WE'RE NOT, SO, WE'RE DOING A VERY LIMITED NUMBER OF DOSES WHICH IS, YOU KNOW LIMITED BY WHAT THE BUDGET WAS SO YOU REALLY DO NEED TO HAVE MORE EXPENSIVE DOSES TO DO THAT AND MORE TAYLORED TO THE PARTICULAR MODEL WE'RE DOING. WHEN WE'RE TESTING 60 CELL LINES EACH OF THEM HAS A DIFFERENT CONCENTRATION THAT THEY RESPOND TO AND DRUG PREP IS A HUGE, HUGE PART OF COMBINATION SCREENS. SO IT WASN'T POSSIBLE TO DO ANY TAILORING OF CONCENTRATIONS. >> BUT DON'T THEY RECOMMEND THAT YOU TEST AROUND THE INHIBITORY CONCENTRATION 50 AND THAT YOU HAVE A COUPLE CONCENTRATIONS AROUND THAT. >> SO THERE WAS ART IN CHOOSING THE DOSES FOR THESE. SO I'LL GIVE YOU A FLAVOR OF HOW WE DID IT. SO EACH LOCATION DID THOSE DOSE RESPONSE CURVES FOR EACH OF THE AGENTS IN THE CELL LINES SO WE GET A RAIMPLE OF RESPONSE AND WE WANT EVERY CELL LINE, WE WANT TO PICK TRUENESSITRATIONS FOR EVERY CELL LINE HAS SOME RESPONSE BUT NOT EVERY CELL LINE IS COMPLETELY INHIBITED. WE ALSO KEEP IN MIND THE HUMAN ACHIEVABLE C-MAX AND TRY TO MAXIMIZE DOSES UNDER THAT. >> SO MY REAL QUESTION IS WHY DIDN'T THOSE XENOGRAFTS WORK WHEN THE SAME CELL LINE INVITRO WAS JUDGED TO BE SENSITIVE, IS IT A PHARMACOKINETIC ISSUE OR A DOSE SCHEDULE ISSUE OR-- >> OR IT COULD BE THAT YOU EXPLAIN IT BEFORE YOU PUT THE CELL TYPES INTO THE MICE. FOLLOWING THE PASSAGE, THERE ARE SOME GENE CONSTANT BUT FOR EXAMPLE, ABCB-ONE WHICH IS IMPORTANT FOR DRUG EFFLUX, IT'S EXPRESSION DIS APPEARS DURING CULTURE. SO THAT OBVIOUSLY AS A BIG INFLUENCE ON SENSITIVITY TO DRUGS THAT ARE TRANSPORTED BY THAT SO THAT'S WHY IN THE DATA MINING WE'RE LOOKING FOR CASES WHERE THE CELL LINES RESPOND THE SAPPLED FOR THOSE FIVE MODELS BUT THEN DIVERGE FOR THE RESPONSIVE AND UNRESPONSIVE, SO THERE ARE CHARACTERISTICS SPECIFIC TO THE XENOGRAFT TUMORS THAT CAN TELL US WHY? ONE RESPONSE AND ONE DOESN'T. --RESPONDS AND ONE DOESN'T. >> I HAVE A QUESTION ABOUT REDUNDANCY OF MECHANISM OF ACTION. SO IN THE EXAMPLE FOR EXAMPLE, BORTIZAMIBAND THE CLORFARANINE, AND LOOKING AT THE INHIBITOR BECAUSE NOT THAT YOU SAW ONLY WITH THE BORTIZAMIB BUT IF THE PROTEOSOME INHIBITOR GAVE YOU THAT KIND OF THING THEN YOU WOULD HAVE THE CONFIDENCE IT HAD TO DO WITH PROTEOSOME AND MECHANISM WILL SO I'M WONDERING ABOUT THE REDUNDANCY OF MECHANISM OF ACTION, AND THAT'S ANOTHER IMPORTANT POINT SO FOR TWOT SCREENS FOR THE FIRST ONE FOR THE ALMANAC, WE USE TO APPROVE DRUGS BUT IT WAS THE ONLY CHOICE THAT THE TIME THE SCREEN WAS RUN AND THE SECOND SCREEN OF INVESTIGATIONAL DRUGS WE HAVE MADE AN EFFORT TO TRY AND COLLECT INVESTIGATIONAL AGENTS OF MULTIPLE ONES FOR EACH MECHANISM AND TO LOOK AT THOSE QUESTIONS AND YOU CERTAINLY DO SEE SIMILARITIES. ESPECIALLY FOR TARGETED AGENTS, KINASE INHIBITORS, MOST WILL INHIBIT THE TARGETING SYSTEM THEATPEOPLE ARE THINK BEING IT FOR BUT THEN MAYBE TWO OR THREE OTHER ONES. SO THOSE MIGHT BE DIFFERENT FOR THE NEXT INHIBITOR THAT TARGETS THAT KINASE SO THE CELL LINE CAN PICK APART. >> IT WILL GIVE YOU A DIFFERENT PILOT PROJECT POT SIS DEPENDING ON WHAT YOU SAW--TO WHAT THE-- >> RIGHT, RIGHT. >> OTHER COMMENTS OR QUESTIONS? >> THANK YOU. >> THANK YOU VERY MUCH. >> DO YOU ANTICIPATE WHEN THE DATA WILL BE DEPOSITED PUB LI >> FOR THE ONLINE WE'RE WAITING FOR FINAL RESULTS FROM THE PHARMACODYNAMICS GROUP. >> OKAY, WE WILL MOVE NOW TO A COUPLE PRESENTATIONS ON THE EXPERIMENTAL THERAPEUTICS CLINICAL TRIALS NETWORK. FIRST PERCY IVY WILL PROVIDE AN UPDATE ON THE LAUNCH OF THIS NEW PROGRAM AND THEN WE'RE GOING TO HEAR FROM JEFF CHAP HIRE O FROM CAN DANA-FARBER, I WAS GOING TO TALK ABOUT ON THE NEW CLINICAL TRIALS TRIALS THUT PUKICS NETWORK. >> SO GOOD AFTERNOON. I WILL SPEAK ABOUT THE NCI'S EXPERIMENTAL CLINICAL TRIALS NETWORK AND THE GOAL OF THIS NETWORK IS THE RE COMPETED SERIES OF GRANTS OF THE WERE THE AND DEVELOPMENT OF NEW CANCER PATIENTS. WE WANT TO EXTENTIVELY CHARACTERIZE TUMORS AND BIOMARKER DRIVEN STUDIES. WE WANT TO ENHANCE OUR UNDERSTANDING OF CANCER BIOLOGY AND THEN ANOTHER MAJOR GOAL WOULD BE EDUCATION AND TRAINING OF YOUNG INVESTIGATORS. WE ALSO RECOGNIZE FROM OUR PAST EXPERIENCE THAT THERE ARE GOING TO BE A NUMBER OF CHALLENGES THAT REFLECT THE REALITY OF DRUG DEVELOPMENT AT THIS POINT IN TIME AND THE FIRST IS ACTUALLY ACCRUAL AND ONE OF THE REASONS WE MOVE TO A NETWORK BASED MODEL WAS THAT WE WERE GOING TO HAVE SMALLER AND SMALLER PATIENT POPULATIONS WITH VERY CLEARLY MODEL CITIZEN LEAKULARLY DEFINED DISEASES AND THAT IT WOULD BE MORE AND MORE DIFFICULT FOR A SINGLE INSTITUTION TO ACCRUE THESE PATIENTS SO THEY WANT TO THE ABILITY TO RAPIDLY EXPAND STUDIES INTO A NETWORK. SO WE WERE LOOKING AT A SCALE AND FLEXIBLE PRESENTLY ARABLE PROGRAM TO ACCOMPLISH THAT GOAL. THE NEXT IS A CHALLENGE BUT PEOPLE RISING TO THE CAUSE IS THE EVALUATION OF BIOMARKERS AND CLINICAL TRIALS. THEY CAN ACQUIRE IMAGING AND THAT LEADS TO MULTIPLE BIOPSIES AND THAT CAN BE CHALLENGE NOTHING A CLINICAL SETTING AND THE FINAL THING WE WANT TO BE ABLE TO DO IS IN A MUCH MORE FASTER FASHION, TRANSLATE WHAT WE SEE CLINICALLY BACK TO THE BASIC RESEARCH OR IF THEY'RE NEW AND VERY INTERESTING BASIC FINDINGS, THEN MORE RAPIDLY TRANSLATE THOSE INTO THE CLINIC. SO THIS IS THE NCI AND CTEP DRUG DEVELOPMENT PORTFOLIO, I SHOW YOU THIS NOT TO READ IT ALL TO YOU BUT THAT WE HAVE A BROAD PORTFOLIO, IT COVERS A VARIETY OF CELL RECEPTORS AND SIGNALING PATHWAYS THAT EFFECT APOPTOSIS SURVIVAL, MIGRATION AND ANKIO GENESIS, AND PROTEIN TURNOVER AND IMMUNO MODULATION AND DNA REPAIR AND EPIGENETICS. ONE OF THE THINGS AND WE HAVE TO STRECTEN IS THE ABILITY TO PERFORM COMBINATION STUDIES WITH INVESTIGATIONAL AGENTS AND HAVING A BROAD PORTFOLIO, ALLOWS US TO MORE EASILY ACCOMPLISH THIS GOAL. SO THIS IS A GENERAL PARADIGM FOR HOW WE'RE TRYING TO APPROACH CLINICAL TRANSLATIONAL RESEARCH AND CANCER BIOLOGY. AND IF YOU LOOK AT THIS TRIAL, WE WANT THEM AT THE START OF THE STUDY TO HAVE TUMOR AVAILABLE OR ANALYSIS OF PATHWAY ACTIVATION OR BIOMARKER EVALUATION THEN ONCE A PATIENT IS ASSIGNED TO A CLINICAL TRIAL BASED ON MOLECULAR CHARACTERIDESSATION AND I USE THAT TERM VERY, VERY BROADLY, THEY WILL INITIATE TREATMENT AND THEN DURING THE COURSE OF THEIR TREATMENT WE WILL MONITOR THOSE PATIENTS AND OBTAIN ANOTHER BI OPPOSITE SCHEIN A TIME WHEN BIOPSIES OCCUR OR ARE INDICATED BY THE GREEN ASTERISKS IN THE UPPER RIGHTCORNER OF THE BOXES AND DURING PATIENT MONITORING WE WILL LOOK FOR A NUMBER OF THINGS, PROOF OF MECHANISM, PROOF OF CONCEPT BUT THE OTHER THINGS WE WILL LOOK FOR IS EMERGENCY OF RESISTANCE OR THE DEVELOPMENT THE SIGNALING TO COMPENSATORY PATHWAYS FOR THE REVIVAL THOSE KINDS OF THINGS AND THE FINAL THING WE DO TO CONTEXT OF THESE IS TO MONITOR THOSE PATIENTS AND UNDERSTAND AFTER THEY COMPLETED THEIR THERAPY, WHY DID THEY RESPOND OR BECOME RESISTANT AND DEVELOP PROGRESSIVE DISEASE. BECAUSE MY UNDERSTANDING THOSE THINGS WE WILL BE ABLE TO SELECT THE NEXT AGENT THEY MAY NEED TO RECEIVE IF IT'S AVAILABLE CLINICALLY OR TO HELP US BETTER DEFINE WHAT KINDS OF COMBINATION THERAPY AND ACTIVITIES AND PROJECTS WE WANT TO MOVE FORWARD WITH IN THE FUTURE. SO ON THE FAR RIGHT I'VE GIVEN YOU EXAMPLES OF NONCLINICAL MODELS OR THE TYPE OF MODEL CITIZEN LEAKULAR CHARACTERIZATION AND ON THE FAR LEFT ARE THE CLINICAL OBSERVATIONS WE ROUTINELY MAKE IN THE CONFIXTURE OF THE STUDY. SO HOW DID WE CHANGE OUR SYSTEM. I THINK PERHAPS ONE OF THE MOST IMPORTANT THINGS WE DID IS DECIDED TO TAKE A MUCH MORE TEAM BASED APPROACH TO DEVELOPMENT. TO THAT END WE DEVELOPED A PRETTY SIMPLE MODEL FOR CLINICAL TRIALS, AND WHAT WE WANTED OUT OF THAT MODEL WAS A GROUP OF CLINICIANS WITH EXPERTISE AND TRIALS AND CLINICAL MANAGEMENT AND WE WANTED TRANSLATIONAL SCIENTIST WHO IS MAY HAVE A VERY STRONG CLINICAL BENT THAT COULD HELP US WITH BIOMARKERS OR CHARACTERIZING THE PATIENTS WE ARE ALREADY TREATING AND FINALLY WE WANT TO LEVERAGE THE WORK OF THE CANCER BIOLOGIST, IN PARTICULAR THOSE THAT HAVE NCI BASED PEER REVIEWED FUNDING AND THAT COULD BE EITHER OUT OF THE RO-1 GRANT POOL OR OTHER PORTS OF THE GRANT POOL, SPORES OR THE CANCER CENTER. WE ALSO TO MAKE THIS FUNCTIONAL HAD DEVELOPED A SOCIALIZED SUPPORT SYSTEM THAT AT THE END I'LL TOUCH ON VERY, VERY, BRIEFLY SO THIS SAY MODEL THAT WE USE TO HAVE A TEAM BASED APPROACH. SO THERE ARE TWO PLACES WHERE WE USE THIS MODAND HE WILL THIS IS A PROCESS FLOW DIAGRAM BUT THE FITTER IS INTERNALLY WE BRING A NEW DRUG INTO THE SYSTEM. THERE'S AN NCI PROJECT TEAM IF YOU WILL MADE UP THE SAME GROUP OF PATIENTS, PEOPLE THAT PARTICIPATE IN THE PROJECT TEAM SO THEY'RE CLINICIANS, PEOPLE WITH DISEASE SPECIFIC EXPERTISE PEOPLE WITH CLEAR EXPERTISE AND TRANSLATIONAL WORK AND WE ALSO WORK CLOSELY WITH THE BIOLOGIST AND THE PROGRAM DIRECTORS THAT MANAGE SPECIFIC GRANT PORTFOLIOS THAT WOULD HAVE AN IMPACT ON A SIGNALING PATHWAY, WE WERE TRYING TO INTERROGATE SO OUR HOPE IS ACROSS THE SYSTEM TO LEVERAGE EVERYONE TO PARTICIPATE. ONCE THIS KIND OF PRELIMINARY WORK IS DONE WE PROCEED WITH THE NEXT STEP AND WE START WORK ONAUR REGULATORY AGREEMENTS. SO THE EXTERNAL OR EXTRAMURAL PROJECT TEAM IS THE ONE I WILL SPEND A LITTLE BUILT OF TIME TABLING ABOUT TODAY, THAT TEAM ALSO HAD A CLINICAL TRANSLATIONAL CANCER BIOLOGY COMPONENT AND WHAT WE HAD CHOSEN TO DO, RATHER THAN SEND OUT MAP SOLICITATION IS TO SEND OUT A REQUEST OR FORM AFRONS PROJECT TEAM AND A REQUEST FOR PEOPLE TO APPLY FOR MEMBERSP TO THAT PROJECT TEAM AND THAT GROUP OF INDIVIDUALS IS EVALUATED AND COMPETITIVELY AND WE SELECT THE PROJECT TEAM BASED ON THE INDIVIDUAL SKILL AND ABILITY IN VERY SPECIFIC AREAS, EARLY CLINICAL TRIALS. BIOMARKER DEVELOPMENT WITH THAT PARTICULAR DRUG OR AGENT, AND WE ALSO IDENTIFY A BASIC SCIENTIST EXPERT THAT CAN HELP US BETTER INFORM OUR SELECTION OF BIOMARKERS OR THINGS THAT WE NEED TO BE LOOKING AT IN ADDITION TO JUST THE VERY BASIC WORK IN DOING EARLY CLINICAL TRIALS. SO I WILL SHOW YOU THIS AS AN EXAMPLE, AS WE THOUGHT ABOUT THIS, WE HAVE SIX MONTHS TO DEVELOP OUR AGREEMENTS SO OUR GOAL WAS TO MOVE FROM ABOUT 26 DOWN TO 15 MONTHS. WE ARE TRYING TO CUT OFF ABOUT SIX MONTHS OF TIME. SO WE WERE GOING TO CONCURRENTLY DO CREATIVE DEVELOPMENT AND HAVE THE PROJECT TEAM WORK TO DESIGN HOW THE NCI WAS INITIALLY GOING TO BRING A NEW DRUG INTO DEVELOPMENT SO THIS IS AN EXAMPLE OF A RECENT PROJECT TEAM AND THIS IS A TIMELINE. IT FIRST CAME INTO THE SYSTEM IN JANUARY. IT WENT THROUGH THE PROJECT TEAM PROCESS. THERE WAS VERY INTENSIVE SET OF MEETINGS IN THE MIDDLE OF THAT THAT DEFINED WHAT CLINICAL TRIALS WOULD BE PERFORMED AND WHAT TYPE OF BIOMARKERS WE WOULD BE DOING AND IT WAS THEN PRESENTED TO THE STEERING COMMITTEE, THE INVESTIGATIONAL DRUG STEERING COMMITTEE AND BASICALLY FROM THE TIME THE DRUG TAME INTO THE SYSTEM TO THE TIME IT WAS FINALLY APPROVED FOR DEVELOPMENT AT THE NCI, WAS 9.5 MONTHS. SO WE'VE ACTUALLY TRUNCATED OUR TIMELINE EVEN FURTHER. SO IT'S THEN, I THINK A RELATIVELY EFFICIENT SYSTEM FOR APPROACHING NEW DEVELOPMENT OF THESE DRUGS. THIS IS AN EXAMPLE OF THAT PROJECT TEAM. WE WILL HAVE SOMEONE ELSE JEFF SCHAPO SPEAK ABOUT A PROJECT TEAM EXPERIENCE BUT IN THIS WE WERE ABLE TO DO--IDENTIFY CLINICIANS WITH EXTENSIVE EXPERTISE, THIS IS AN AGENT THAT HITS THE T79 TISSUE THAT SMALL CELL LUNG CANCER WE HAD PEOPLE WITH EXTENSIVE EXPERIENCE IN TRANSLATIONAL WORK AND WE ALSO BASIC SCIENTIST THAT HAD NCI PEER REVIEWED FUNDING TO HELP INFORM US ON HOW WE SHOULD LOOK AT THE MUTATIONS WE WERE SEEING, WHAT KIND OF MODELS WERE OUT THERE, THAT WOULD HELP US BETTER DEVELOP THESE DRUGS, SO WE WERE ABLE TO GARNER, I THINK REALLY NATIONAL AND INTERNATIONAL LEVEL, EXPERTISE TO ASSIST US IN THE DEVELOPMENT OF THIS SPECIFIC AGENT AND IT ALSO WORKS FOR OTHER PROJECT TEAMS WE HAD. SO, I WILL TALK A LITTLE BIT ABOUT BIOMARKERS AND HOW WE'VE BEEN THINKING ABOUT THOSE IN THE CONTEXT OF EARLY PHASE CLINICAL TRIAL. THAT WAS ONE OF OUR GOALS AND OBJECTIVES THROUGH THE NETWORK AND WE BASICALLY HAVE SEGGREGATED THEM AND REASONABLY STRAIGHT FORWARD FASHION AND INTERVAL INTEGRATE AND EXPLORATORY. SO EACH TRIAL WHEN THE INVESTIGATOR SENDS IN APPLICATION WE DECIDE WHAT KIND OF BIOMARKER THEY'RE GOING TO PERFORM IN THEIR CONTEXT OF THEIR STUDY, AND THEN THEY WILL BE A STUDY USED FOR PATIENT SELECTION AND USED TO DETERMINE TREATMENT IF ANY OF THOSE ARE THE CASE THEN IT'S AN INTEGRAL BIOMARKER. IF IT'S INTEGRATED IT WILL BE HYPOTHESIS GENERATION AND USED TO DESCRIBE THE PATIENTS THAT ARE BEING TREATED IN THE CLINICAL TRIAL. IN THAT SITUATION, IT CAN BE PERFORMED IN A CLEAR READY ENVIRONMENT WHERE AN INTEGRAL BIOMARKER USED FOR SELECTION WILL HAVE TO BE PERFORM INDEED A CLEAR ENVIRONMENT AND FINALLY WE HAVE BIOMARKERS THAT ARE EXPLORATORY. THEY'RE INTERESTING, THEY'RE CLEARLY RELATED TO MECHANISMS BUT WE REALLY DON'T HAVE A SUFFICIENT AMOUNT OF INFORMATION TO MOVE THEM FORWARD FOR CLINICAL DECISION MAK. AND THEN WE ASK THAT OUR PROJECT TEAM ACTUALLY PRIORITIZE THE BIOMARKERS SO IF YOU CAN DO ONE, WHICH ONE DO YOU WANT TO DO. WHAT ARE THE MOST IMPORTANT IMPORTANT QUESTIONS TO BE ASKED OR ANSWERED WITH THE BIOMARKERS IN THE CONTEXT OF THE CLINICAL TRIALS. SO THEY'RE ASKED TO PRIORITIZE THEIR BIOMAR THEY CAN LOOK AT PROOF OF MECHANISM IF THAT'S THE MOST IMPORTANT THING, THEY CAN LOOK AT GENOMIC CHARACTERIZATION AND LOOK FOR SPECIFIC MUTATION OR DELETIONS OR TRANSLOCATIONS, WHATEVER, OR THERE MAY BE INSTANCES WHERE WE'RE GOING TO LOOK AT NONINVASIVE IMAGING ASSESSMENTS. SO THIS A LIST OF AGENTS THAT ARE COMING ON TARGET WITH THE SYSTEM, JEFF WILL SPEAK ABOUT THE ATT-1 837 WHICH IS AN HFP90 INHIBITOR WHICH HAS GONE THROUGH THE WHOLE SCIENCE PROCESS, THEN IT CAME IN AS SOLICITATION AND WE HAD A LOT OF CONTACTS BASED DISCUSSIONS USING THE INFERNAL PROJECT TEAM TO DISCUSS HOW THAT SHOULD BEST BE DEVELOPED AND WE MOST LEE HAD THE AFT RAZENNICCA 9291 WHICH IS AN EGFR INLIBRARY FOUNDATIONITTOR, IT'S A THERD GENERATION AND IT CIRCUMVENTS RESISTANCE AND WE HAVE ASPECTS THAT INTERROGATE ATMR AND DMET AND INHIBIOR AND THOSE ARE ALL PREPARING OR SLOTTED TO GO INTO PROJECT TEAM BASED DEVELOPMENT THIS WILL BE MY ONLY NOD INTO DATA MOTITTORRING AND INFRASTRUCTURE, WE HAVE DATA MONITORING FOR CLINICAL TRIAL AND HOW WE APPROACH GATHERING THE DATA ON THE CLINICAL STUDY. SO BASICALLY IT'S A WEB BASED SYSTEM O IT'S NO LONGER SEGGREGATED OUT INTO INDIVIDUAL SILOS BUT IT'S A SINGLE CENTRALIZED WEB BASED REPORTING SYSTEM FOR MONITORING CLINICAL TRIAL. SO VICTORYS COME IN USING AN I. A. M. ACCOUNT. THEY WILL GO TO THE CTSU WEB SITE WHICH IS THE CLINICAL TRIALS SUPPORT UNIT AND THEY CAN LOCATE CLINICAL TRIALS ON WHICH THEY CAN ENROLL PATIENTS. ALSO ONCE WE APPROVE A TRIAL WE HAVE A CENTRAL IRB THAT REVIEWS AND APPROVING ALL OF THIS TRIALS THAT WE'RE LAUNCHING. THAT, LOWS US TO OPEN EVERY TRIAL NETWORK WIDE AND TO BASICALL ONLY DEAL WITH ONE IRB. WE HAVE OPEN PATIENT DATA CESS AND WE REVAMPED HOW THAT IS OCCURRING AND THIS ALL HAD TO INTERDIGITATE WITH PREEXISTING ENTERPRISE SYSTEMS WITHIN THE NCI INCLUDING OUR ADVERSE EVENT REPORTING SYSTEM. SO A LITTLE BIT ABOUT MEDY DATA RAVE, WE MOVED FROM PAPER TO A PAPER FREE SYSTEM AND REVAMPED HOW THAT DATA IS PRESENTED TO US. SO IN THE WEB BASED REPORTING SYSTEM, YOU CAN SEE THAT ENROLLMENT BY SITE, LOOK AT ADVERSE EVENTS BUT YOU'RE LOOKING AT THEM IN A SPECIFIC CONTENT, YOU'RE LOOKING AT THE COURSE OF THERAPY, THE TOXICITY AND HOW MANY PATIENTS HAD THAT TOXICITY IN THE CONTEXT OF A CLINICAL TRIAL SO THAT CAN YOU VISUALLY SEE WHAT AN ADVERSE EVENT PROFILE LOOKS LIKE FOR A SINGLE PATIENTAGE AGENT AND A TRIAL. AND YOU CAN USE THE CAP LANMEYER CURVE AND WILL GENERATE AT END OF A STUDY, A FINAL STUDY REPORT THAT HAS AGGREGATED ALL OF THE DAT CONTEMPORANEOUSLY OVER THE LIFETIME OF THE CLINICAL TRIAL. THESE ARE THE FACE WOB SITES AND THE NETWORK LAUNCHED AND RECOMPETED PHASE ONE PROGRAM ASK STARTED ON MARCH FIRST OF THIS YEAR WE'RE OVER SIX MONTHS BOT PROCESS AND YOU KNOW ALL NEW PROCESSES HAVE LITTLE HICK UPS BUT I THINK THAT THINGS ARE GOING REASONABLY WELL, AND WE'VE BUILT 15 OR SO PROTOCOLS AND MEDIDATA RAVE AND WE'VE HAD TEAMS COME THROUGH THE PROCESS AND WE ARE MOVING ALONG. SO THE LAST THING I'LL TALK ABOUT IS WE FELT THAT SINCE THIS WAS A TOTAL NEW PROCESS, AND WE WERE USING A NEW SYSTEM SO WE WANT TO EVALUATION, IDENTIFY COURSE CORRECTIONS FOR THE NETWORK AS A WHOLE AND TO PROVIDE DATA TO DEVOID DECISION MAKING FOR PROGRAM'S SUBSEQUENT FUNDING CYCLE. SO WE'RE GOING TO BE EVALUATING FOUR KEY DOMAINS, ADOPTION AND IMPLEMENTATION AND VALUE ADDED HOPEFULLY AT THE T-SCIENCE BASED APPROACH. WE WILL MONITOR CLINICAL TRIAL PERFORMANCE AND WE HAVE DEVELOPED SOME MEASURES OF NETWORK SYNERGY TO SEE HOW WELL OUR NEWLY FORMED TEAM IS WORKING WITH EACH OTHER. SO I THINK THAT IS MY LAST SLIDE. I WOULD BE DELIGHTED TO TAKE ANY QUESTIONS. , QUESTIONS? >> SO PERSE YOU I INCLUDED FUNCTIONAL IMAGING AS A BIOMARKER BUT ONE EXAMPLE YOU SHOWED YOU DID NOT HAVE IMAGING EXPERTS IN THERE, AND READ IT QUICKLY, THOUGH, AND I'M WOBDER WHETHER IT'S ANOTHER SITUATION WHERE YOU WANT YOUR CLINICAL TO INFORM YOUR CLINICAL STUDIESENTIOUS SPECIALLY GIB OW EXPENSIVE IT IS IN THE CLINICAL TRIALS IT MIGHT BE A USEFUL TEAM APPROACH. >> ABSOLUTELY. SO WE DID NOT HAVE EXTERNAL IMAGING EVALUATORS BUT WE DID HAVE SOME OF THE PEOPLE IN THE CANCER IMAGING PROGRAM THAT PROVIDED US ADVICE AND INPUT. BECAUSE IT WAS A PRETTY--IF I REMEMBER CORRECTLY IT WAS A REASONABLY STANDARD IMAGING TECHNIQUE, AND SO WE DID NOT BRING IN AN OUTSIDE EXPERT BUT THERE ARE--THERE'S ONE THAT PROBABLY WILL COME UP SOON WHERE WE'RE LOOKING AT ETH-MYSO WHICH IS NOT WIDELY USE AND WE WILL SEEK ADDITIONAL INPUT AND EXPERTISE IN THAT AREA AND I THINK THAT'S A SITUATION WHERE THE PRIN CLINICAL TEST IS A RELATIVELY CHEAP FEASIBILITY BEFORE YOU GO TO TRIAL. ESPECIALLY WHERE THINGS ARE STARTING TO DO NCTN GROUPS WHERE THEY'RE FORM THAT SO THEY HAVE BEEN TALKING ABOUT THAT. >> THANK YOU. >> SO THANK YOU FOR YOUR PRESENTATION, IN JUST SEEING THE--VERY IMPRESSIVE RESOURCES AND THINGS THAT YOU'RE MARSHALING AROUND THESE PROGRAMS, YOU KNOW I THINK A COUPLE OF POINTS THAT I'M STRUCK BY, ONE IN TERMS OF THIS BEING A PATHWAY TO RAPIDLY CREPED DRUGS, I DON'T THINK THAT'S NECESSARILY WHAT YOU SET UP HERE, BUT WHAT IS VERY IMPRESSIVE AND I THINK CAN BE VERY INTERESTING IN TERMS OF COLLABORATION WITH INDUSTRY PARTNERS IS A--THE ABILITY TO DO TRANSLALLY RICH SCIENTIFIC, YOU KNOW BASICALLY CLINICAL SCIENTIFIC EXPERIMENTS AND THINGS. WHICH IS ACTUALLY AN IMPORTANT NEED BECAUSE WE'RE TYPICALLY RUSHING, JUST TRYING TO GET IN PHASE ONE OR TWO DOSE AND VERY FOCUSED ON GOING AS RAPIDLY AS POSSIBLE AND THEN WE CERTAINLY TRY TO BUILD IN BIOMARKERS AND THINGS TO MAKE BETTER DECISIONS BUT TO REALLY GO TO THIS LEVEL AND THINK SCIENTIFICALLY ABOUT THE STUDY, IS MUCH HARDER FOR US TO DO THOSE TYPES OF STUDIES IN INDUSTRY. SO I THINK THAT'S--I DON'T KNOW IF YOU THOUGHT ABOUT HOW THIS SORT OF SYNERGIZES WITH YOUR PARTNERS AND THINGS. >> CERTAINEE WE HOPE TO WORK CLOSELY, OBVIOUSLY BOTH OF THE DRUGS WE TOG TALK ABOUT AND JEFF WILL TALK ABOUT ARE GOVERNMENT-INDUSTRY PARTNERSHIP THROUGH A CREDA AGREEMENT. SO THAT'S OUR REAL GOAL IS TO PROVIEDMAN THAT VALUE ADDED, IN PARTICULAR IN THE AREA OF BIOMARKERS. >> I WAS STRUCK BY THE INTEREST APPROACH WHICH IS ESSENTIALLY PEACE MEAL SELECTION OF INDIVIDUAL WHO IS CAN CONTRIBUTE UNIQUE ATTRIBUTES. THAT IS A LITTLE BIT DIFFERENT THAN WHAT IT COMMONLY DONE WHICH HAS WOULD BE TO SOLICIT PREFORMED TEAM TO BASICALLY SAY WE CAN DO THAT, HERE'S WHAT WE CAN BRING. IS THERE ANYWAY TO ASSESS THE RELATIVE SUCCESS OF THE APPROACH YOU'RE TAKING VERSES WHERE WOULD HAVE BEEN THE MORE TRADITIONAL APPROACH. >> SO MY VERY LAST SLIDE WHICH I ZOOMED THROUGH, WE ARE EVALUATING THAT. WE'RE LOOKING AT EACH PART OF THE PROCESS. WE JUST COMPLETED A SET OF INTERVIEWS WITH ALL OF THE INDIVIDUALS THAT ACTUALLY PARTICIPATEDOT PROJECT TEAMS AND INTERNAL NCI PEOPLE TO GET A READ ON HOW THAT IS WORKING FOR THEM. ARE THE TIME COMMITMENTS REASONABLE? AND THEN, YOU KNOW I THINK TIME WILL TELL IF THIS IS THE BEST OR MOST EFFICIENT PROCESS. IT LOOKS TO BE WORKING WELL AND EFFICIENTLY, BUT I THINK WE HAVE TO SEE OVERTIME, HOW QUICKLY DO WE GET THE PROTOCOLS IN. HOW QUICKLY TO PROTOCOLS OPEN? WHEN THE TRIAL IS COMPLETED, DO WE ACTUALLY GET VERY VALUABLE ADDITIONAL INFORMATION OUT OF THAT. SO MY GESHTALT IS THAT WE'RE TOO EARLY IN THE PROCESS TO MAKE A DEFINITIVE STATEMENT THAT THIS IS THE BEST AND MOST FABULOUS WAY TO GO BUT I WOULD SAY THAT I THINK IT IS MOVE NOTHING THE DIRECTION WE ANTIC. AND IT HAS BEEN--IT HAS EXSEATED OUR EXPECTATIONS WITH REGARD TO EFFICIENCY OF THE PROCESS. THE OTHER THING IS THE AMOUNT OF TIME COMMITMENT FOR THESE, REALLY QUICK TEAMS THEY'RE NOT LIKE LONG STANDING TEAMS OF PEOPLE WHO ARE GOING TO GET TO KNOW EACH OTHER AND WORK TOGETHER FOREVER AND OVER AND EVERY. BUT THEY REALLY ASSEMBLE AND THEY HAVE TO FINISH THEIR WORK IN SIX MONTHS AND IT'S ASTONISHING THAT ONE OF THEM FINISHED ALL THEIR WORK IN 9.5 MONTHS. SO THAT'S GREAT. WE EXCEEDED OUR EXPECTATIONS THERE. SO I'M WONDERING ABOUT THE IMPACT OF HAVING A LACK OF CONTINUITY BY DESIGN IN TERMS OF GETTING THAT SORT OF VIRTUES ONITY AND EXPERTISE AND HISTORY OF WORKING TOGETHER THAT ARE ACTUALLY FACILITATES THINGS WORKING MORE EFFECTIVELY DOWN THE ROAD. >> SO MY IMPRESSION WE HAD CERTAINLY NOT TESTED THAT THEORY YET IS THAT WHEN WE ASK FOR PEOPLE THAT ARE DOING RESEARCH IN CERTAIN AREAS, WE ARE REQUESTING TO APPLY BROADLY BUT THERE WILL BE GROUPS OF PEOPLE THAT HAVE SPECIFIC AREAS OF EXPERTISE THAT WILL BE REUSED. EXPETER EASE IN LUNG CANCER MODELS OR BROAD EXPERTISE IN THE DEVELOPMENT OF RESISTANCE TO STANDARD THERAPIES IN LUNG CANCERS SO, I DON'T THINK THAT THOSE PEOPLE WILL BE DIFFERENT EVERY TIME WE DO IT, AND SO IF I HAD TO GUESS, I GUESS THAT SOME OF THEM WILL BE REUSED BUT NOT ALL OF THEM SO IT GIVES US A FRESH LOOK, GIVES US THE OPPORTUNITY FOR A FRESH LOOK AND THEY THERE WILL BE CONTINUITY. SO I HOPE IT WORKS. >> SO I'D LIKE TO-- >> ONE MORE QUESTION, IT'S PROBABLY TOO EARLY BUT ANY SENSE OF WHAT THE BAND WIDTH IS, THE PROCESS LOOKS WELL DEFINED AND MOVES TOO RAPIDLY BUT IN TERMS OF COMPOUNDS OR STUDIES YOU COULD BE RUNNING WITH THE NETWORK? >> SO IN TERMS OF BAND WIDTH, CERTAINLY I THINK THE MOST LOGS WE BROUGHT IN EVER WITHIN A YEAR HAS BEEN AROUND 15 OR 20. THERE IS OBVIOUSLY I'M SURE YOU'RE ALL AWARE OF THE NEW PROCESS OF BRINGING NEW DRUGS TO THE NCI THROUGH THE NEXT PROGRAM, THE EXPERIMENTAL THERAPEUTICS PROGRAM AND THAT IS BASICALLY LIMITED BY WHAT COMES IN THROUGH THAT SYSTEM. SO SO FAR THIS YEAR, WE'VE HAD THE ONES THAT I LISTED ON THIS SLIDE COME IN THROUGH THAT SYSTEM. AND WE'RE REVIEWING MORE AND AS THEY COME IN AND THEY'RE REVIEWED BY THE NEXT AND GO THROUGH THAT PROCESS TO BE BROUGHT INTO THE NCI FOR DEVELOPMENT, I THINK THEIR BAND IDTH AND PRETTY BROAD AND IF THERE IS ANY LIMITATION IN THE BAND WIDTH WILL IT BE LIMITATION IN THE BUDGET THAT ALLOWS US TO PURSUE IT. OKAY, I'D LIKE TO INVITE DR. SCHAPIRO WHO WILL GIVE A PRESENTATION ON HOW TO RESEARCH OR INVOLVED JEFF IS DIRECTOR OF EARLY DRUG DEVELOPMENT CENTER AT DANA-FARBER. I'M GOING TO TALK ABOUT THE CLINICAL TRANSLATIONAL RESEAR% IN THIS PROGRAM. SO AS A PHASE ONE DIRECTOR, TWO MAIN REASONS WHY I'M VERY EXCITED TO BE PART OF THE ETCTN, AND DECIDED TO BE PART OF THIS. AND A LOT OF THIS WAS JUST COVERED BUT I THINK THE CREATION OF THESE DRUG SPECIFIC PROJECT TEAMS AIS AFFORDING AN OPPORTUNITY TO CONTRIBUTE TO A VERY COLLABORATIVE NETWORK WITH VERY SUBSTANTIAL INPUT INTO THE DRUG DEVELOPMENT PLAN. ADDITIONALLY IT'S IMPORTANT TO POINT OUT THIS IS INCLUSIVE OF JUNIOR INVESTIGATORS AND THIS IS IMPORTANT MECHANISM FOR LEADING EARLY PHASE PROGRAM TO INVOLVE JUNIOR INVESTIGATORS AT OUR SITES. AND A SECOND ISSUE IS THAT I WOULD LIKE TO COVER IS THAT THE CTEP PROGRAM PROVIDES LEVERAGE TO FOSTER DEVELOPMENT OF NOVEL DRUG COMBINATIONS THAT WILL MAKE RESULTS AND MIGHT NOT BE TRANSLATED TO CLINICAL TRIAL. SO I THINK THE ETCTN PROVIDES THESE TWO OPPORTUNITIES WHICH IS WHY MANY OF THE SITES INVOLVED RIGHT NOW ARE EXCITED ABOUT THE PROGRAM. THERE'S A LOT OF VERBIAGE ON THIS SLIDE BUT IT'S IMPORTANT TO TAKE A LOOK AT THE WAY THING VS CHANGED FROM BEFORE MARCH FIRST TO THE WAY THINGS ARE HAPPENING NOW. SO IN THE OLD PROGRAM ARE THE LEGACY PROGRAMS, YOU KNOW FROM A PERSPECTIVE OF AN INVESTIGATOR, NCI CTEP WOULD PROCURE THE AGENT AND THEN GET LOIs FOR PREDEFINED TRIALS THAT WERE NOT ALREADY INCORPORATE INTO THE INDUST'S DRUG DEVELOPMENT PLAN, THAT IS THE MASSIVE SOLICITATIONS THAT PERCY MENTIONED SO THIS WOULD SUBMET COMPETITIVE LOIs AND THESE REQUIRED A GREAT DEAL OF PREPARATION THAT WOULD HAVE TO BE EXTENSIVE PRECLINICAL DATA JUSTIFYING THE CLINICAL PROPOSAL THERE HAD BE DETAILS OF THE EXECUTION AND BIOSTATTISTICAL CONSIDERATIONS AND ALL THAT WENT INTO THE LOI TO THE POINT THAT MANY OF US WERE RIGHTING NEXT TO WHAT WAS A GRANT PROPOSAL. AND OF COURSE THE PROCESS THEN HAD A SUBSTANTIALLY HIGH FAILURE RATE BECAUSE ONLY A SMALL NUMBER OF LOIs WERE APPROVED AND THIS AWIVE RESULT INDEED SUBSTANTIAL INVESTIGATION FRUSTRATION ESPECIALLY AT THE JUNIOR LEVEL. I THINK THE PROJECT TEAM MECHANISM IS A GOOD WAY TO MAKE THIS BETTER FOR US. SO RIGHT NOW, WHAT HAPPENS IS INVESTIGATORS APPLY SIMPLY TO BE A NUMBER OF THE PROJECT TEAM AND WE APPLY A BASIC TRANSLATIONAL OR CLINICAL SCIENTIST ASK THEN NCI, COMPET TESTIFY TO GET ON TO THE PROJECT TEAM BUT NCI ASSUMABLED THE PROJECT TEAM AND THE PROJECT TEAM TAKES ON A COUPLE OF GOALS, ONE WOULD BE TO ASSESS THE PRECLINICAL PACKAGE, DETERMINE IF OTHER WORK IS NEEDED AND THE SECOND MAJOR GOAL THEN WOULD BE TO PROPOSE IVE DISEASE BASE OR BI'S MARKER BASED CLEANICAL TRIALS AND THAT WOULD PKPD END POINTS. SO THE PROJECT TEAM DOES ALL THAT WORK OF WHAT ARE THE CLINICAL TRIALS GOING TO BE, WHAT ARE THE DESIGNS GOING TO BE, HOW WILL THEY LOOK, DRUG DEVELOPMENT PLAN IS PRESENTED TO THE IDFC, ONCE WE HAVE THE STAMP THEN PEOPLE GO BACK AND PREPARE DETAILED LETTER DETAILS ABOUT THESE TRIALS. SOPHISTICATED SO THAT THE WORK IS NOT SO GREAT. IT DOESN'T AND RATHER THERE'S PARTICIPATE IN THE PLAN OF WHAT THAT WILL BE, HOW THE DRUG DEVELOPMENT PACKAGE WILL LOOK AND NOT UNTIL THERE'S AGREEMENT AMONG INVESTIGATORS, AT MULTIPLE SITES OF THE NETWORK, BEFORE THE LOIs AND BEFORE THE TRIALS ARE WRITTEN. I WAS INVOLVED IN THE FIRST DRUG SPECIFIC PROJECT TEAM, AS FIRST YOU MENTION THE INHIBITOR, AT-1 33887. THIS IS ONE OF THE SECOND GENERATION RESOURCE COMPOUNDS IT'S A POTENT HSP INHIBITOR, IT IS COMPANY THAT'S BEEN DEVELOPING IS AZTECS, AND THEIR CURRENT PLAN ON THEM AND LUNG CANCER ALONG WITH CROZOTINIB, AND LOOKING AT IT WITH IMATINIB AND WITH CRPC ABIRATERONE. WHEN THEY TOOK THIS, THEY GOT TOGETHER, THEY IDENTIFIED AREAS THAT REALLY HAD NOT BEEN ADDREED FOR HSP 90 INHIBITORS, VERY WELL, OR YOU KNOW REALLY THEY THOUGHT NEEDED MORE ATTENTION BASED ON WHAT WAS ON THE LITERATURE SO THESE WERE SOME OF THE IDEAS THAT THE INTRAMURAL TEAM HAD PUT FORWARD AND THAT WAS POTENTIALLY TO ELECTRIC AT HSP INHIBITOR IN THE NONHODGKINS LYMPHOMA. THERE'S ALSO MANTEL CELL LYMPHOMA WHERE CDKFOUR COULD BE A CLIENT OR THE LYMPHOMA WHERE BCL SIX COULD BE A CLIENT. SO THESE WERE AREAS WHERE THEY HAVEN'T INVESTIGATED. BUT THERE WAS DATA IN THE LITERATURE THAT HSP 90 MAY BE USEFUL IN TRIPLE NEGATIVE BREAST CANCER HERE WHERE THEY MAY NOT BE JUST ONE DOM IN FACT RECEPTOR TYROSEEN KINASE, THERE MAY BE MULTIPLE PATHWAYS OF SIGNAL TRANSDUCTION INVOLVED MANY OF WHICH INVOLVE HSP 90 CLIENTS AND BASED ON DATA IN THE LITERATURE IT WAS THOUGHT THAT MAYBE THIS PROGRAM OUTTO LOOK AT HSP 90 INHIBITOR AND TRIPLE NEGATIVE BREAST CANCER. WHILE MOST OF THE WORK ON LUNG CANCER WAS DRIVEN ON LUNG CANCER THERE WAS DATA SHARINGA IN EGFR IN THE SUBSET AND THAT HAD NOT BEEN LOOKED AT WELL AT ALL IN PREVIOUS TRIALS. SO IT WAS THOUGHT THAT THAT MIGHT BE A WHERE CTEP COULD CONTRIBUTE. AS YOU KNOW THERE ARE MUSEUM TACTS THAT HAVE DENOEE RESISTANT TO THE INHIBITORS. ANOTHER ENTIRE SET OF HSP 90 SENSITIVE PROTEINS ARE THOSE INVOLVED IN THE DNA DAMAGE RESPONSE AND THIS HAS NOT BEEN LOOKED AT VERY CAREFULLY WITH HSP 90 INHIBITION AT ALL AND IT WAS THOUGHT THAT HSP 90 AS A MECHANISM AS A MEANS TO MODULATE THE DNA DAMAGE RESPONSES MIGHT OF USE AND THE IDEA THAT PUT FORWARD WHEN THE CTEP SOLICITED THE PROJECT TEAM MEMBER APPLICATION WAS FOR CHEMO RADIATION IN THE SQUAMOUS CELL CANCER OF THE HEAD AND NECK. SO THESE WERE THE FOUR IDEAS THAT THE INTERNAL TEAM PROPOSED AND THESE WENT OUT IN THE PROJECT TEAM MEMBER APPLICATIO SO PEOPLE THAT WERE INTERESTED IT WORKING IN THESE AREAS AND THESE WERE PEOPLE THAT APPLIED WITH OTHER IDEAS OF THE PROJECT TEAM AS WELL. AFTER THE APPLICATIONS WERE PUT TOGETHER THIS IS THE TEAM THAT WAS ASSEMBLED SO PEOPLE APPLY AGAIN BASIC SCIENTIST, TRANSLATIONAL SCIENTIST, CLINICAL SCIENTISTS AND OTHER MEMBERS AS WELL. SO WE JUST LOOK AT CLINICAL SCIENTIST LIST THERE SO THERE WAS ONE GROUP THAT WAS CHOSEN THAT HAD HEAD AND NECK EXPERTISE FOR COMBINATION TRIALS AND LILLIAN WASEUR CLINICAL LEADER WITHIN THIS PROGRAM. THERE WAS ANOTHER GROUP, ANOTHER PAIR OF INVESTIGATORS CHOSEN BASED ON INTEREST AND WORK NOTHING THIS--WITH DRUG IN LYMPHOMAS. THERE WAS ONE OF SEVERAL APPLICATIONS WAS CHOSEN TO POTENTIALLY PUT TOGETHER A PROPOSAL IN NONSMALL CELL LUNG CANCER AND THIS WAS THE GROUP IN TRIPLE NEGATIVE BREAST CANCER AND THERE WERE OTHER INVESTIGATORS BOTH FROM WITHIN AND WITHOUT THE NCI, THAT WERE RECRUITED AS CLINICIANS TO CONTRIBUTE TO THIS AS WELL AND WHAT YOU'LL NOTICE IS IN THE GROUP THAT WAS EVENTUALLY CHOSEN FOR EACH GROUP THERE WAS A JUNIOR INVESTIGATORS PAIR WIDE THE SENIOR INVESTIGATOR. SO HERE, THE JUNIOR INVESTIGATORS ARE IN BOLD AND PAIRED WITH SENIOR INVESTIGATOR HERE AND IT WAS A STRONG ATTENTION AND THROUGHOUT THIS WHOLE PROGRAM IS STRONG INTENTION TO LEADERSHIP ROLES AND TRIALS THAT WILL BE DONE BY JUNIOR INVESTIGATORS ALONG WITH SENIOR MENTORSHIP. AND NOW WE ALSO HAD BASIC SCIENCE MEMBERS OF THE TEAM THAT WERE RECRUITED SO WE WERE FORTUNATE TO HEAD AND NECK INVOLVED AND THE NCI AND HE IS ONE OF THE LEADERS NATIONALLY IN HSP 90 DEVELOPMENT AND IN BIOLOGY AND WE ALSO HAD ANOTHER INVESTIGATOR FOR UNIVERSITY OF MICHIGAN WHO CONTRIBUTED A LOT TO HELPING THEM UNDERSTAND A LOT OF BASIC SCIENCE BETWEEN THE INHIBITION AND WE LEARNED A LOT TO THESE TWO INVESTIGATORS AND THE GOAL OF HELPING TO PRIORITIZE AND WORK ON BIOMARKERS, THAT WOULD YOU KNOW FIT INTO ALL THE TRIALS. I HAD BEEN INVOLVED IN ONE OF THEM--AS INDUSTRY SPONSORED PHASE ONE STUDIES OF AT-1 3387 AND THIS IS PRODUCE A CONONICLE BIOMARKER INHIBITION AND SO I SERVED AS TRANSLATIONAL LEAVE IN THIS GROUP BUT WE ALSO HAD DAVID CAR BONE AND GORED AN MILLS AND CARTER FROM THE NCI AND ALL THESE PEOPLE HELPED IN DESIGN OF THE BIOMARKERS FOR THESE STUDIES. ADDITIONALLY THERE WERE RADIATION ONCOLOGY LEFTS AND WE WERE MADE AVAILABLE FOR THE CHEMO COMBINATION AND WE DID HAVE PEOPLE THAT HADKS EATER EASE IN IMAGE AND WAS ASKED THE PREVIOUS QUESTION WAS ABOUT NONINVASIVE IMAGING THAT MIGHT BE INCORPORATE INTO THESE TRIALS OR PRECLINICAL WORK AND WE HAD IMAGING INVESTIGATORS AS WELL AND THEN WE ALSO HAD A BIOSTATISTICIAN INVOLVEMENT. THIS WAS ALONG WITH CTEMMEMBERS AND THIS WAS THE INVESTIGATOR FOUR AT-1 3387 AND JAMIE PLAYED A PART IN THIS AS WELL AND THEN HELP FROM AMY. AND WE MENTIONED CAREER DEVELOPMENT INVESTIGATORS ON THE TEAM AND AND THESE PEOPLE PLAY IMPORTANT ROLES IN THE ULTIMATE DESIGN OF THE STUDY AND THERE ARE ATTEMPTS TO IDENTIFY INVESTIGATORS ASSOCIATED WITH SPORES WHOO ARE USED TO AND THE WAY THE TEAM WAS CONSTRUCTED IT IS A LARGE GROUP OF PEOPLE AND I THINK IT WORKED QUITE WELL. THIS IS HOW WE DID OUR WORK, WE FIRST ENDED UP WITH A LONG PERIOD ON ONE CALL WE FOCUSED ON THE LYMPHOMA TRIPLE KNEVE BREAST CANCER AND TRIALS ASK WHAT THEY MIGHT LOOK LIKE AND ABOUT I O MARKERS MIGHT BE CONSIDERED AND WE DID THAT A SECOND CALL FOR HEAD, NECK AND LUNG CANCER THOSE WERE DISCUSSED TOGETHER. THEN WE WERE CALLED WITH OTHER CLINICAL INVESTIGATORS THAT WERE IN THE ETCTN NETWORK WHO APPLIED TO THE TEAM AND DIDN'T NECESSARILY GET ON TO THE TEAM. BUT WE KNEW THAT WE WERE GOING TO NEED THEM TO THE CLINICAL TRIAL AND SO WE TOOK THE PAINS TO ACTUALLY HAVE FOUR DISEASE BASED CALLS WHERE WE INVITED INVESTIGATORS AND WE KNEW FROM APPLICATIONS THEY WERE INTERESTED IN WORKING ON THE DRUG IN THOSE AREAS AND WE GAVE THEM ONE PHONE CALL AND GET THEIR INPUT AND HOPEFULLY GENERATE THEIR EXCITEMENT FOR ULTIMATELY PARTICIPATE NOTHING THE TRIAL WHICH MIGHT INVOLVE ENTIRE NETWORK. WE HAD ADDITIONAL PRECLINICAL CALLS THAT CALL FOR HEAD AND NECK PROPOSAL AND THESE WERE OTHER IDEAS THAT WERE SENT INTO THE PROJECT TEAM WHICH THERE WASN'T A WAY FOR TIME, TIME TO CONSIDER BUT WE HAD HAD READS PROPOSED AND OF NOVEL COMBINATIONS OF WAYS TO ABNORMALITIES BROIGATE HSP70 INTO HSP90 INHIBITION AND OTHER STRATEGIES TO MAKE THEM DO THAT AND MAKE THEM WORK BETTER ADDITIONALLY WITH THE INHIBITION, WITH EFFECTS AND REPAIR WE HAD PROPOSALS THAT LOOK AT THE INHIBITION WITH THE REPAIR AND INHIBITOR, WE DID TAKE AT LEAST SOMETIME TO HAVE A BIT OF DISCUSSION ABOUT THESE IDEAS AND WHAT MIGHT BE NEEDED TO DEVELOP THEM FURTHER BUT ULTIMATELYY COULDN'T DO THIS BECAUSE THEY WERE OUTSIDE OF THE REALM THAT WERE CHOSEN TO GO FORWARD FOR CLINICAL TRIALS. THIS CULMINATED INTO FOUR PROPOSALS THAT WE PRESENTED TO THE INVESTIGATIONAL DRUG STEERING COMMITTEE SO LYMPHOMA THERE WAS A MODEL THERAPY BASE TO STUDY WITHOUT POSITIVE LYMPHOMA, MANTEL CELL LYMPHOMA AND BCL AS THREE SEPARATE ARMS AND TRIPLE NEGATIVE BREAST CANCER WAS A PHASE ONE, WAS A MONOTHERAPY STUDY FOLLOWINGED BY TAXATION COMBINATION FOR THAT DISEASE. LUNG CANCER PROPOSAL WAS WITH ERLOTINIB FOLLOWING A RUNNING, AND THEN WE DECIDED TO HAVE 20 PATIENTS WITH THESE INSERTION MUTATIONS TO BE EVALUATED AND THEY RESPONDED POORLY THEY MAKE MAKE A MAJOR IMPACT WE INCLUDED THOSE AS WELL IN THE PLAN. AND REPAIR COMBINATION WE FOCUSED ON AGAIN HEAD AND NECK AND THERE WAS PHASE ONE STUDY WITH CHEMO RADIATION THAT ULTIMATELY WAS PROPOSED. THE BIOMARKER PRIORITIZATION SIMILAR TO THE SLIDE THAT SHOWED YOU IT WAS FELT THAT WE FIRST HAD A REALLY FOCUS ON PROVE OF MECHANISM AND SO INDUCTION OF HSP SEIVET AND TUMOR BIOPSIES SERS GOING TO BE IMPORTANT WHERE WE MIGHT NOT ALWAYS GET TO THE MONOTHERAPY RECOMMENDED DOSE WE WERE GOING TO LOOK AT DEPLETION OF CLIENTS TO REDUCE RESPONSE OF THESE BENEFITS IN THESE PROGRAMS, SO THIS WOULD BE INDUCED EXPRESSION OF DNA REPAIR PROTEIN IN COMBINATION OF CHEMO RADIATION THESE ARE ALL HSP CLIENT OPEN SOURCE SOFTWAREY WE WANT TO LOOK AT REDUCED EXPRESSION OF THESE PROTEINS. AND MUTE NIGH FR AND WE WANT TO LOOK AT MUTINY EGFR AND THIS HAD BEEN CHOSEN HAS WORKED ON A PLASMA BASE PROTECTION AND THAT WILL BE INCORPORATED INTO THE STUDY, NONENVASIVE WAY OF LOOKING AT PLASMA DNA TO LOOK AT THE EGFR AS WE'RE TREATING WITH THE DRUG, SO WE'RE GOING TO HAVE REDUCED EXPRESSION OF LYMPHOMA DRIVERS AND REDUCED EXPRESSION OF BREAST CANCER DRIVES AND DETERMINANTS THAT COULD AFFECT THE RESPONSE TO TAXAIN. SO THE PROOF OF MECHANISMS WERE THE PRIORITY. IN SOME TRIALS WE WILL ENCLUED GENOMEECS AND THIS WILL BE EASIEST TO DO IN THE TRIAL WHICH IS A MONOTHERAPY STUDY AND WE MAY TRY TO SEPARATE OUT RESPONDERS FROM NONRESPONDERS WITH WHOLE EXOME SEQUENCING AND WHOLE TRANSCRIPT OHM ASSESSMENT FOR PATHWAY ADAPTATION AND TREATMENT BIOPSIES AND AGAIN IN THIS MONOTHERAPY STUDY IN PATIENTS WHO RESPOND WE WILL INCORPORATE BIOPSIES AT THE TIME OF RESIEVANCE AND TRY TO UNDERSTAND RESISTANCE IN PEOPLE WHO MIGHT HAVE ACHIEVED CLIPICAL BENEFIT. FINALLY WE ALSO DISCUSSED WITH OUR IMAGING COLLEAGUE, NONINSVASIVE ASSESSMENT AND A THYMA DINE PET AS A PET ISOTOPE THAT GO INTEREST THIS AND THIS WILL BE MOST RELEVANT IN A LYMPHOMA STUDY, ESPECIALLY WHERE CDKFOUR IS A TARGET AND THERE'S CELL CYCLE ARREST AND PET WOULD BE A NOVEL WAY OF ARRESTING CELL CYCLE ARREST WHEN WE DEPLETE THE CDKFOUR FOR LYMPHOMA CELLS AND IN THE OHIO STATE GROUP LOOKED AT THE PET AS A MARKER OF RESPONSE FOR TRIPLE NEGATIVE BREAST CANCER STUDIES IN THE PAST AND THIS WILL BE INCORPORATED INTO THE BREAST CANCER STUDY SO THESE WERE THE BIOMARKERS THAT WERE ULTIMATELY UG JESTED TO BE INCORPORATED INTO THE VARIOUS TRIALS. THE TEAM ALSO CAME UP WITH RECOMMENDATIONS AND IT WAS FELT THAT MORE WORK WAS NECESSARY FOR THE SAFETY OF SIS PLATIN COMBINED WITH AT-1 3387 AND PRECLINICAL HEAD AND NECK CANCER MODEL AND THAT WORK IS GOING ON THIS IS GOING ON NOW AS THE HEAD AND NECK CANCER IS BEING PUT TOGETHER AND REVIEWED. AND AS A MENTIONED THERE WERE COMBINATIONS THAT WERE PROPOSED AND DISCUSSED PRECLINICAL IN VIVO WORK THAT MIGHT BE NEEDED TO ULTIMATELY MORE DEFINITIVELY BRING THOSE FORWARD TO CLINICAL TATION NOW AS PERCY MENTIONED THIS IS A NEW SYSTEM AND THESE ARE ISSUES THAT CAN COME UP WHEN WE'RE WORKING IN THESE PROJECT TEAMS SO IN AN ATTEMPT TO BE INCLUSIVE, CTEMHAD GENERATED AND CONSTRUCTED A TEAM THAT WAS FAIRLY LARGE IN NUMBER. SO THERE THIS TO BE SELECTION OF BE MEMBERS AND PEER REVIEW GRANTS IN THE FIELD AND THEN THEY BECOME UNWIELDY AS YOU SAW THEY HAD FOCUSED ON HEAD AND LUNG AND NECK AND ONE THAT FOCUSED ON TRIPLE NEGATIVE BUST CANCER AND THE CALL HIS TO BE SUBSETTED TO DEAL WITH A FAIRLY LARGE PROJECT TEAM SIZE. BUT THE DOWN SIDE IS YOU CAN'T BE DO SELECTIVE AND APPLIED TO THE TEAM WHO CAN'T GET ON AND HAVE EVERY SITE REPRESENTED IN EVERY TEAM SO AS I MENTIONED THE WAY WE GOT AROUND THAT IS WE DID HAVE ONE CALL WHERE WE ENGAGED INVESTIGATORS WHO WOULD APLAY TO THE TEAM TO EDUCATE THEM ABOUT WHAT WE'RE DOING IS HOPEFULLY GENERATE EXCITEMENT ONCE AS THE INITIAL PLANS WERE REACHING MATURITY. IT WAS ALSO PREVIOUS MENTIONED THAT IT'S A SHORT CONSTRICTED PERIOD OF TIME AND PUT THESE TOGETHER TO WORK THROUGH THE BIOMARKERS TO HAVE EVERYBODY AGREE ON WHAT THE TRIAL WILL LOOK LIKE THIS WAS A LOT OF CALLS IN A ONE MONTH PERIOD AND A VERY HEAVY TIME INVESTMENT AND YOU CAN IMAGINE THERE WERE MEMBERS OF THE TIMA CO-WORKERSED ON THESE PLAN AND THEN DON'T END UP WITH THE TRIAL TO LEAD SO THIS REQUIRES QUITE A BIT OF ACADEMIC GENEROSITY, COMRATRY AND IT IS FORCING PEOPLE TO WORK TOGETHER AS A NETWORK SO THAT EVERYONE CAN ULTIMATELY BEN FATE. THOU THE OTHER SIDE OF THIS IS THAT IF THE INITIAL IDEA THAT ONE HAS OR YOU DON'T GET A NEW TRIAL OUT OF THE INITIAL CONTRIBUTION, DO YOU HAVE THE--THERE'S THE GREAT ABILITY TO ENGAGE THE JUNIOR INVESTIGATIONS HERE THAT I THINK MAKING UP FOR THAT AND THEN, YOU KNOW THE ABILITY TO INTERACT WITH SO MANY BASIC AND TRANSLATIONAL INVESTIGATORS TO CRYSTALLIZE EXPERIMENTS AND INFORMED DRUG DEVELOPMENT. I THINK EVERYBODY BENEFITS FROM THAT AND SOME OF THESE SOME OF THESE POSITIVES I THINK OUTWEIGH THIS POTENTIAL NEGATIVE AND AGAIN ALONG THOSE LINES THERE'S VARIOUS PRIORITIES OF PROJECT TEAM MEMBERS SO NOT EVERY IDEA CAN BE DEVELOPED AND THIS REQUIRE THAD THERE BE STRONG LEADERSHIP REQUIRED FROM BOTH CTEP AND THE PEOPLE THAT WERE CHOSEN AS THE PROJECT TEAM LEADERS AND ADDITIONALLY THERE'S THE ABILITY TO SEND IN LETTERS OF INTENT LATE THEY'RE DON'T COMPETE WITH THE PROJECT TEAM'S PLAN SO THAT ONE CAN SEND IN OTHER PLANS LATER IF YOU CAN'T GET YOUR IDEA DEVELOPED DIRECTLY BY THE PROJECT TEAM SO THERE'S WAYS AROUND IT THAT'S STILL THE ABILITY TO CO CONTRIBUTE. WE HAVE ONE MORE PRESENTATION, WE HAVE UNTIL THREE, I WAS WONDERING IF YOU COULD MOVE ON QUICKLY. >> SO THE THING I DID WANT TO COVER WAS THE COMBINATION AND I THINK THAT IT'S IMPORTANT TO POINT OUT THAT CTEP CAN LEVERAGE VERY GOOD PRECLINICAL DATA TO PUT TOGETHER NOVEL DRUG COMBINATIONS THIS IS THE TIP OF THE ICEBERG, THIS IS FOUR THROUGH OUR OWN SITE AND WE DON'T HAVE GO THROUGH THEM ALL IN THE INTEREST OF TIME BUT NOVEL CONITRATIONS EMANATING FROM TRANSLATIONAL WORK THAT HAVE NOW TRANSLATED INTO THE CLINICAL TRIALS SO THEY'RE NOT BEING LEFT ON THE PAGES OF CANCER CELL OR NATURE MEDICINE BUT THESE ARE WORKING INTO CLINICAL TRIALS. I THINK THAT ONE--THAT'S WORTH MENTIONING BRIEFLY IS THE CEDIRANIB/OLAPP A RIB TRIAL. SO THESE ARE COMING OUT OF THE GRANTS FUNDING MECHANISMS AND THESE ARE WAYS THAT THE PHASE ONE PROGRAMS IN THE INSTITUTIONS CAN INTERACT WITH DISEASE BASED PROGRAMS. AND FOR THE PROGRAM, THERE'S GOOD CLINICAL DATA THAT THE DRUGS COULD BE SINNER GESTIC IN PRECLINICAL MODELS AND THIS LED TO PHASE ONE TRIAL AND ARANDOMMIZED PHASE TWO TRIAL AND PLATINUM SENSITIVE OVARIAN CANCER WHERE THEY DID QUITE A BIT BETTER THAN MONOTHERAPY, YOU WILL SEE THE HAZARD RATIO AND THIS IS ONE WHERE THIS WOULD NOT HAVE BEEN DONE WITHOUT THE PROGRAM AND ONE NOW THAT IS MOVE INTOG PHASE THREE REGISTRATION STRATEGIES. AND THERE'S MANDATORY BIOPSIES AND ANGIOGENIC MARKERS WILL BE LOOKED AT TO GET MECHANISTICALLY WHAT IS HAPPENING WITH THIS COMBINATION. FINALLY IT'S IMPORTANT TO SEE THESE AT HARVARD AND YALE AND THESE WILL BE ANALYZING GENOMIC LEVELS FOR VARIOUS TRIALS BUT THESE ARE BIOMARKER HUBS AND THEY WILL BE ABLE TO CONTRIBUTE OTHER ASSAYS AS WELL AS TIME GOES ON. SO IN SUMMARY THE PROJECT TEAM MODCELL COLLABORATIVE AND INTERACTIVE AND IMPROVEMENT OF THE OVER THE OLD SYSTEM. IT'S HIGHLY ADVANTAGEOUS FOR THE ETCTN TO DRAW IN MULTIDISCIPLINARY TEAM OF SENIOR LEADERS BUT ALSO I THINK IT'S IMPORTANT TO STRESS THAT CONTRIBUTIONS OF THE JUNIOR INVESTIGATORS THAT'S INVITED INTO THIS PROGRAM AND PRIORITIZED. WE ONLY TOUCHED BRIEFLY BUT CTEP HAS THE ABILITY TO DEVELOP INNOVATIVE COMBINATIONS AND THIS IS EXCITING FOR MEMBERS OF ETCTN PROGRAM AND PERCY MENTIONED VERY BRIEFLY SOME OF THE OPERATIONAL IMPROVEMENT THAT WILL FACILITATE RAPID ACTVIATION AND ROBUST ACCRUAL WHEN NECESSARY. SOPHISTATED ARE SORTING SIGNALS WE IF I WENT OVER MY ALLOTTED TIME. >> IT'S A GREAT BRIE SENTATION AND YOU SEGUED BEAUTIFULLY INTO THE NEXT PRESENTATION WHICH I WILL ASK DR. MASSETT TO STEP UP TO TALK ABOUT ACCRUAL TO THE EARLY THERAPEUTICS PROGRAMMING. WE'VE TOUCHED ON A NUMBER OF TIMES TALKING ABOUT ACCRUAL TO LATE PHASE TRIALS BUT THERE'S A CORRECTIVE ACTION PLAN FOR EARLY PHASE TRIALS THAT IS CLOSELY CONSIDERED I THINK BY THE GROUP BY THEN THERE WILL BE ACCRUALCHALLENGES SO INTERESTED TO HEAR WHAT THE PLANS ARE. >> THANK YOU, GOOD AFTERNOON. I'M HAPPY TO BE HERE AND WRAPPING UP THE DAY AS THE LAST SPEAKER. THE GOOD NEWS THAT DR. IVY PRESENTED A FEW OF THE SLIDES IN MORE THUNDERSHOWER ONESS AND THAN I KNOW--THOROUGHNESS SO I CAN SKIP PASSED A FEW. SO THE FIRST THING I WOULD LIKE TO TALK ABOUT IS WE ARE DOING A THREE YEAR PROCESS EVALUATION OF THE ETCTN. WE WERE APPLIED FOR AND AWARDED FUBBEDS FOR THE NIH EVALUATION PROGRAM AND PERCY TALKED ABOUT THE FOUR DIFFERENT BUCKETS THAT WERE EVALUATING SO JUST IN BRIEF, LOOKING AT THE PARTICIPANTS ENGAGED. ARE THEY SATISFIED WITH IT, ARE WE EMPELEMENTING IT AS WE EXPECTED AND THEN FOR THE TEAM SCIENCE APPROACH BECAUSE IT'S SO NEW IN THE CLINICAL TRIAL ARENA AS WELL AS ACROSS NIH. WE WILL EVALUATING THE IMPACT OF THAT ON THE SATISFACTION OF THE PROGRAM. BUT THE THIRD BUCKET ARE THE CLINICAL TRIAL PERFORMANCE METRICS WHICH YOU ARE LOOKING AT SO ARE THE TRIALS MEETING THEIR GOALS IN AN EFFICIENT MANNER AND WHAT CONTRIBUTES TO THE SUCCESS OR CHALLENGES OF ACCRUAL TO A CHILD AND THE LAST BUCKET IS THE SYNERGY BECAUSE NETWORK CONCEPT IS NEW TO THE CLINICAL TRIAL SYSTEM HERE AS OPPOSE TO THE INDIVIDUAL ORGANIZATIONS THAT WE HAD PREVIOUSLY, WE WILL BE LOOKING AT OVERTHE COURSE OF THE THREE YORES, HOW DOES THIS NOTE WORK DEVELOPMENT AND HOW COLLABORATIVE ARE THE ORGANIZATIONS KNEESATIONS WITHIN IT. THERE ARE SIX TASKS JUST BRIEFLY DOING QUARTERLY DATA REVIEW. WE WILL BE ESTABLISHING BASELINES USING ARCHIVAL DATA FROM THE PREETCTN TRIALS. WE ARE DOING ANNUAL FIELD SURVEY WITH FOLK WHO IS ARE PARTICIPATE NOTHING THE NETWORK AS WELL AS INTERVIEWS AND THEN THE DRUG DEVELOPMENT PLAN WHICH YOU JUST HEARD A LOT ABOUT WILL BE DOING MILESTONE REVIEWS FOR EACH OF THE PLANS THAT HAVE BEEN DEVELOPED. THE IMPETUS FOR THE EVALUATION AND 2010 INSTITUTE CONSENSUS GOALS FOR RECOMMENDING NCI FOR THE TRANCE FORMED SYSTEM OF THE CLINICAL TRIALS. SO IF YOU LOOK HERE THE TRIAL DESIGN, PRIORITIZATION, PARTICIPATION AND IMPROVING SPEED AND EFFICIENCY OF THE CONDUCT OF THE TRIAL. SO FOR THE REST OF THE PRESENTATION I WILL I HIGHLIGHT THIS LAST ONE LOOKING OUT FOR EARLY PHASE TRIALS. HOW THE GUIDELINES FOR SLOW ACCRUAL ARE IMPLEMENTED. AS YOU KNOW THERE'S BEEN QUITE A BIT OF WORK DONE AND PRESENTED HERE FOR THE NCTN ON THE PROTOCOL DEVELOPMENT AS EARLY AS MARCH OF THIS YEAR, DRS. MOONEY ABOUT THE ACCRUAL GUIDELINES FOR THE LATE FIZZ TRIAL. SO WHAT WE'RE TALKING ABOUT IS A CORRECTIVE ACTION PLAN AND ANALYSIS OF THAT, FOR THE EARLY PHASE TRIALS. SO JUST AS A BRIEF BACKGROUND, PART OF THE OPERATIONAL EFFICIENCY WORKING GROUP. CTEP BEGAN TRACKING IN 2010 THE POST ACTIVATION FOR THESE ACTIVITIES FOR THESE EARLY PHASE TRIALS TO GIVE INFORMATION TO THE PORTFOLIO PERFORMANCE FOR THE IDB TRIALS. AND THEN ALSO WHAT THEY DID WAS IMPLEMENT THIS PROCESS CALLED DIRECTIVE ACTION MANS IF THE TRIAL IS SLOW ACCRUING WE WILL SEND A REQUEST FOR ACTIVE PLAN TO THE FIs OF THE STUDIES AND AT A HAVE TO RETURN IT WITHIN TWO WEEKS IDIDN'TIFYING REASONS AND POSSIBLE ACTIONS THEY'RE GOING TO TAKE TO IMPROVE THE ACCRUAL TO THEIR TRIAL. SO THE 2010 GUIDELINES ARE FOR PHASE ONE AFTER 2-QUARTERS, IF THEY'RE ACCRUING LESS THAN 50% OF THE ACCRUAL RATE, THEY WILL RECIPH A CORRECTIVE ACTION PLAN, FOR PHASE TWO TRIALS, IF AFTER 3-QUARTERS THEY WILL GROW IN LESS THAN 50%, THEY WILL ALSO RECEIVE THE CORRECTIVE ACTION PLAN. SO TO GET A TENSE OF THESE CORRECTIVE ACTION PLANS, IT'S A REQUEST THAT WE GET A LETTER BACK AND THEY DESCRIBE THIS WITHIN THE LETTER SO THE GOAL OF THE ANALYSIS WAS TO LOOK AT CHALLENGES IDENTIFY INDEED THESE CAPS AND PROVIDE GUIDANCE TO THE NEW ETCTN. SO WANTING TO CATEGORIZE THE SLOW ACCRUAL REASONS AND ACTIONS IN THE CAPS AND DOCUMENT METRICS OF TRIALS THAT RECEIVE THE CORRECTIVE ACTION PLAN FOR. SO THE SAMPLE WHERE THE IND STUDIES THAT WERE ACTIVE BETWEEN AUGUST 2011 AND FEBRUARY 2013 WHICH YIELDED A TOTAL OF 327 STUDIES OF THOSE, 46% ASKED FOR A CAP REREQUEST AND WE RECEIVED 135 THAT WERE ELIGIBLE FOR ANALYSIS AND 41% OF THE TRIALS TRIALS DURING THIS TIME FRAME. SO WE CODED THE CAP REASONS AND ACTIONS, WE LOOKED AT TIMELINE AND ACCRUAL DATA FOR THE PHASE TRIAL AND WORKED WITH IDB TO CODE WHETHER OR NOT THOSE WERE CLOSED HAD MET THEIR PRIMARY SCIENTIFIC OBJECTIVE. SO THE TRIALS WE HAD, 50% WERE PHASE ONE, MOST EVALUATION PROCESS THEM WERE ADULT TRIALS. THE MEDIAN TRIAL ACTIVATION DATE WAS OCTOBER 15th 2010 AND AT THE TIME OF ANALYSIS, WHICH WAS FEBRUARY 24th OF THIS YEAR, 70% ARE CLOSE TO ACCRUAL, I'LL GET INTO HA THAT MEANS IN A MOMENT MPLET SO HOW LONG WERE THESE TRIALS OPEN FOR. IF YOU LOOK AT THIS SLIDE, THE GREEN BARS REPRESENT THE TOLLAL NUMBER OF MONTH FOR THE TRIAL. THE BLUE WERE THE PRE-CAP, AND THE RED IS POST-CAP. SO THE CAP REQUEST WAS SENT AND RECEIVED PRETTY MUCH MISS OF HOW LONG THE TRIAL WAS OPEN FOR. FOR THE PHASE TWO, THE CAP WAS SENT AND RECEIVED EARLIER THAN HALFWAY THROUGH THE TRIAL. SO THE BIG QUESTION IS, DID THE ACCRUAL RATE CHANGE PRECAP TO POST CAP. SO THE WAY WE BROKE IT DOWN WAS LOOKING AT FOR PHASE ONE TRIAL, I'LL MENTION BLUE AND FIRST. 71% OF THE TRIALS HAD AN INCREASE POST CAP OF LESS THAN HALF A PATIENT A MONTH. NOW FOR PHASE ONE THAT'S NOT TOO SURPRISING BECAUSE THEY HAVE LOW ACCRUAL GOALS TO BEGIN WITH BUT THEY DID HAVE ALMOST 30% OF THE TRIALS TO INCREASE A HALF A PARTY TO THREE PATIENTS A MONTH FOR THE PHASE TWO TRIALS AND THE RED, A THIRD OF THEM INCREASED LESS THAN HALF A PATIENT A MONTH AFTER THEY RECEIVE THE CAPS BUT ALMOST AFUL INCREASED TO HALF A PATIENT TO THREE PATIENTS A MONTH AND THEN 17% DID INCREASE THREE PATIENTS MORE THAN THREE PATIENTS A MONTH AFTER THE CAP. SO THE TIME NEEDED, IT WAS TIME NEEDED FOR MINIMUM ACCRUAL FOR THE EARLY PHASE TRIAL AND MINIMUM ACCRUA IS IMPORTANT BECAUSE IT'S A MARKER THAT IS MOSTLY IMPORTANT FOR, YOU KNOW REACHING THE GOALS, FOR THE PRIMARY SCIENTIFIC OBJECTIVE, SO FOR PHASE ONE TRIALS, ON THE LEFT, THE MEDIAN NUMBER MONTH REACHING MINIMUM ACCRUAL WAS FIVE MONTHS HOWEVER THEY WENT ON TO TAKE 16 MONTHS TO MEET THEIR MINIMUM ACCRUAL GOALS. SO FOR PHASE TWO THE MEDIAN NUMBER OF MONTHS PROJECTED TO REACH MINIMUM ACCRUAL FOR EIGHT MONTHS AND THEN THEY WENT TO TO TAKE 22 MONTHS. SO THREE TIMES LONGER FOR PHASE ONE AND TWO TRIALS. SO HOW DID THIS, THE CAP IMPACT THE PRIMARY SCIENTIFIC OBJECTIVES FOR THESE CLOSE CAP TRIALS. SO OF THE TRIALS THAT WERE CLOSE WHICH WERE 94 OF THEM. PHASE ONE SKETCH% WERE SAID TO HAVE GONE ON TO MEET THE PRIMARY SCIENTIFIC OBJECTIVE. PHASE TWO, 70% WENT TO TO MEET THE SCIENTIFIC OBJECTIVE, HOW LONG DID IT TAKE TO DO THIS. WE COMBINE THEM BECAUSE THEY'RE NO DIFFERENCES BETWEEN THE PHASES, SO THE BARS ON THE LEFT THIS TIME, THE PURPLE, NUMBER 11 REPRESENTS THE NUMBER IT WOULD TAKE TO REACH TOTAL ACCRUAL FOR THE TRIAL AND THE YELLOW BAR WHICH IS 31 MONTH SYSTEM THE MEDIAN NUMBER OF MONTHS THAT ARE ACTIVE TRIALS FOR PRIMARY OBJECTIVE FOR THAT. THOSE PRIMARY OBJECTIVES OTHER THAN NOT MET, IS THE TOTAL NUMBER OF MONTHS WHERE IT'S GOING TO BE FOUR AND INDEED THEY WENT ON TO TAKE 26 MONTHS BEFORE THEY WERE CLOSED. SO THE NEXT ONE COMBINES WHAT WE SAW. SO IF YOU LOOK AT THE LEFT I'LL START WITH BLUE, WHICH IS PHASE ONE. OF THE 33 TRIALS THAT WERE CLOSED AND INCREASED LESS THAN A HALF A PATIENT A MONTH, 58% OF THOSE WENT ON TO MEET THE PRIMARY OBJECTIVE POST KAPS FOR THE 16 TRIALS OF PHASE ONE TRIALS, EIGHT WHO INCREASE, 27% OF THOSE WENT ON TO MEET THE PRIMARY SCIENTIFIC ABJECTIVE, LITTLE DIFFERENT FOR PHASE TWO. 63% OF THOSE THAT INCREASE LESS THAN A HALF A MONTH OR PATIENT A MONTH WENT TO TO MEET THE PRIMARY OBJECTIVES, 63% OF THOSE HAD HALF A PATIENT TO THREE PATIENTS MET THEIR OBJECTIVES, AND THEN ALL OF THE 10 TRIALS THAT INCREASE THREE OR MORE PATIENTS A MONTH, ALL OF THEM WENT ON TO MEET THEIR SCIENTIFIC OBJECTIVES. ANOTHER WAY TO LOOK AT THIS IS SAYING 27% OF THE CLOSED TRIAL HIS AN ACCRUAL IPT GREATER CREASE ASSOCIATE WIDE THE GREATER LIKELIHOOD OF MEETING PRIMARY SCIENTIFIC OBJECTIVE. SO I TOLD THAT YOU WE DID A CONTENT ANALYSIS OF THE CAP, SO BRIEFLY, LOOKING AT PHASE ONE TRIAL, FIRST THIS IS THE HIGH LEVEL REASONS WE FOUND FOR WHY CHILDS ARE SLOW RECURRING AND THAT IS NOT SURPRISING THAT SAFETY AND TOXICITY FOR PHASE ONE TRIAL SYSTEM THE NUMBER ONE REASON FILED CLOSELY BY INSTITUTIONAL ADMINISTRATION PROBLEM, DESIGN AND PROTOCOL CONCERNS AND ELIGIBILITY CONCERNS. FOR THE PHASE ONE TRIAL, 56% OF THE TRIAL HIS TWO OR MORE REASONS GIVEN SO WE WANT TO REMOVE THE SAFETY REASON BECAUSE THAT IS--WAS A PRIMARY REASON FOR THE PHASE ONE AND STILL 3-QUARTERS OF THEM STILL HAVE AT LEAST ONE OTHER REASON FOR SLOW ACCRUAL. SO DOWN GRANULARLY, STRICT ELIGIBILITY AND DELAYS IN TRAFFICKING MANAGEMENT AND FAIL AND YOU ARE EXTENDED IRB DELAYS WAS THE MAIN REASON. NOW SIMILAR ANALYSIS FOR PHASE TWO TRIALS AT HIGHER LEVEL, THE INSTITUTIONAL ADMINISTRATION PROBLEMS WERE THE NUMBER ONE REASON PRETTY CLEARLY FOR WHY THE TRIALS WERE SLOW ACCRUING FOLLOWED BY DESIGN PROTOCOL ELIGIBILITY. PHASE TWO HAD TWO OR MORE REASONS, GOING GRANULAR, STRICT ELIGIBLE AND NOT ACTIVATING WERE THE TOP REASONS SO THE LAUGH ONE ON THIS IS WE WANTED TO LOOK AT THE ACTION SO THEY HAD THE REASON FOR WHY THEIR CHILD WAS SLOW OCCURRING SO WHAT IT WOULD DO ABOUT THEM SO IN THE CODING, PHASE ONE WHICH IS THE BLUE, THE NUMBER ONE REASON THEY DO IS ELIGIBILITY OF THE DESIGN AND TRIAL. FOR PHASE TWO, THE NUMBER ONE WAS ADDING INSTITUTIONS FOLLOWED BY CHANGING ELIGIBLE AND DESIGN OF THE TRIAL. SO OTHER, LAST SLIDE FOR THIS IS TO LOOK AT HOW WELL DID THEY GIVE ACTION, THEY ASSUME THE ACTION STEP WOULD BE RELATED TO IT SO WE TOOK OUT THOSE REASONS THAT WERE OUT OF THE STUDY PIs CONTROL OR THE TEAM AND WE LOOKED AT THOSE THAT WE COULD MAP UP SO ELIGIBILITY, WE LOOKED AT 42 TRIALS AS ELIGIBILITY FOR REASON FOR SLOW ACCRUAL BUT ONLY IN 57% OF THOSE CASES DO WE HAVE AN ACTION STEP THAT MATCHED ELIGIBILITY, AND INSTITUTIONAL ADMINISTRATION PROBLEMS THAT WAS DOWN TO 44% MATCHED AND FOR ADDING SITES AND IRB APPROVAL. 30 OF THOSE TRIALS LIST EXPDZ THEY DID MUCH BETTER, SO IN 73% OF THE DID THEY GO ON TO ACTUALLY HAVE--THEY HAD AN ACTION STEP AND MARCH THE REASON, FUNDING ISSUES IS THE LOWEST AT 22%, I WOULD SAY THAT MOST PEOPLE WOULD ARGUE THAT FUNDINGS OUT OF THEIR CONTROL SO THAT'S WHY IT'S A LOW NUMBER, AND REMOVING SAFETY ISSUES FROM T. HAD 15 TRIALS THAT LIFT THAD AND IN 15% OF THE CASES THOSE MATCH BUT OVERACTIONS MATCH THE REASON 54% OF THE TIME. SO IN SUMMARY, THE CAP TRIALS ARE OPEN A MEDE I CAN'T THINK OF THE 30 MONTHS. TRIALS TOOK A MINIMUM OF THREE TIMES LONGER THAN PROJECTED. OF THEM THEY DID GO ON TO MEET THE SCIENTIFIC OBJECTIVES AND THAT METHOD TOOK THREE TIMES LONGER THAT PROJECTED SO IT'S NOT MEETING IT SO IT TOOK SIX TIMES LONG TORE GO TO THE CLOSE. 27 PERCENT OF ALL TRIALS HAD AN ACCRUAL RATE OF A GREATER LIKELIHOOD OF MEETING THE OBJECTIVE SO PHASE ONE IT WAS EVEN WITH A MODEST INCREASE OF A HALF A PATIENT A MONTH OR MORE AND FOR PHASE TWO AS MORE HAD MORE SUBSTANTIAL INCREASE OF THREE PATIENTS A MONTH. PHASE ONE TRIAL SAFETY TOMIDATEED BUT 3-QUART ARES HAD ONE REASON BEYOND SAFETY AND FOR PHASE TWO, INTUITIONAL AND ADMINISTRATION REASONS TOPPED THE LIST AND JUST OVER HALF REACHED THE CORRECTIVE ACTIONS. SO WHAT DOES THIS MEAN FOR ECTCN. SO THE FIRST IS THAT THE RECOMMENDATIONS ARE TO PROVIDE MORE REALISTIC ACCRUAL PROJECTIONS, SECONDLY DEFINE AND IMPLEMENT AN ACCRUAL PLAN EARLY IN A DEVELOPMENT SO ANTICIPATE WHAT THE PROBLEMS MIGHT BE, HAVE A PLAN OF ACTION FOR THAT AND IMPLEMENT IT IF NEEDED. IN OTHER WORDS DECREASE THE NEED FOR A CAP TO BEGIB WITH. AND THEN THIRD AIM TO BETTER MATCH THE CORRECTIVE ACTION WITH SLOW ACCRUING REASONS WHEN FEASIBLE. BUT ETCTN IS WELL POISED TO ADJUST THESE ACCRUAL CHALLENGES. THE CIRB AS MENTIONED SHOULD REDUCE THE IRB DELAY AND ACCELERATE THE ACTIVATION. AND WE'VE BEEN DOG INTERVIEWS WITH THIS DOES SEEM TO HAVE--IS BEGINNING TO TAKE PLACE. ACCESS TO THE ENTIRE NETWORK CHRKS IS ANOTHER KEY POINT OF THE ETCTN WILL ALLOW MORE SITES TO BE ABLE TO OPEN THE TRIAL AND THEN IN MORE SITES OPEN AND MORE SITE ARE ACCRUING PATIENTS AND THEN THE TEAM APPROACH. IMPROVING QUALITY OF RESPONSE AND OVERALL COMPLETION OF THE EARLY PHASE TRIALS. SO THE NEXT NEXT STEPS ARE A CODING SHEET AND THE COLLECTION AND REASONS AND ACTIONS FOR SLOW ACCRUAL AND DEVELOP STATISTICAL ALGORITHMS TELEVISION EVIDENCE BASED DECISION MAKING FOR TRIAL CLOSURE DUE TO SLOW ACCRUAL. AND FINALLY CONTINUING THE CAPS AS PART OF THE LARGER THREE YEAR ANALYSIS THAT WE'RE DOING THE PROCESS EVALUATION AND INCLUDING NONCAP TRIALS. SO, THAT IS IT. I TRIED TO FINISH EARLY FOR YOU. ANY--WE'RE LOOKING FOR RECOMMENDATIONS REGARDING PROGRAM EVALUATION WE MENTIONED OR THE CAPS ANALYSIS WE DISCUSSED HERE. THANK YOU. >> THANK YOU VERY MUCH. IT'S A LOT OF DATA. VERY INTERESTING DATA. I'M JUST WONDERING FROM YOUR PERSPECTIVE HAVING LOOKED AT ALL OF THAT, DO YOU THINK THAT THE MECHANISM IS WORKING OR DO YOU NEED TO GO BACK TO THE DRAWING BOARD AND REALLY CREATE A SEPARATE MORE ROBUST STRATEGY TO ALTER ACCRUAL TO THESE STUDIES IN A MORE TIMELY AND AGGRESSIVE WAY? >> I THINK THERE'S A LOT OF ANSWERS IN THAT. I BEING --THINK THE FIRST IS THAT THE CORRECTIONS ARE POSITIVE AND THEY HAVE SHOWN IMPROVEMENT TO THE TRIAL I ALSO LOOK AT THE LATE PHASE TRIAL AND WE FIND WHEN PEOPLE ASK TO TAKE A LOOK AT THEIR TRIALS AND REVIEW THEM AT A ACTUALLY ARE DOING IT IN A VERY THOUGHTFUL WAY AND THEY HAVE SAID TO US, YOU KNOW WOW WE HADN'T THOUGHT ABOUT THIS PROCESS, SO THEY LOOK THROUGH IT. AND IT DOES MAKE--THE ACCRUAL JUMP TO ATTENTION SO I THINK THEY DO HAVE POTENTIAL FOR GOOD IMPACT. I THINK SYSTEMATIZING IT MORE WOULD BE THROUGH HOW WE COLLECT THE DATA MIGHT BE HAD HELPFUL AS WELL BUT ONE THING WE TALK TO PERCY ABOUT AND JAMIE IS, HOW CAN WE HELP TRIALS REACH THEIR ACCRUAL GOALINGS BETTER SO THERE'S A LOT OF DATA WE'RE ABLE TO PACKAGE AND SEND BACK SO THEY CAN PUT IT ON THE RADAR ABOUT WHAT TO DO WHEN THEY'RE NOT OTHERWISE THINK BEING IT. >> JUST QUICKLY HAVE YOU LOOKED THE OTHER SIDE OF THE COIN? THOSE THAT CONCLUDED MORE CONVICTLY THAN EXPECTED? WHY THAT HAPPENED? IF YOU ARE TRYING TO GET ACCRUAL PREDICTIONS BETTER, LOOK AT BOTH ENDS OF THE BOTTOM CURVE? >> WE DIDN'T HAVE THAT DATA AVAILABLE TO US FOR THE PREECT NBUT WE ARE COLLECT TAG FOR ECCTN AND THAT WILL BE PART OF THE EVALUATION, SO YES. >> DO YOU KNOW IF THE DRUG THAT WORKS OR THE FACT HOW THE ACCRUAL WAS ON THAT TRIAL. MEANING THE DRUGS THAT ARE NOT GOOD, INVESTIGATOR LOOSES ENTHUSIASM AND IT'S A COMMON PROBLEM? >> I DON'T KNOW FOR THESE. I KNOW THAT LACK OF SCIENTIFIC INTEREST A REASON PEOPLE DON'T ACCRUE BUT WE HAVEN'T SELECT TODAY BUT IT IS SOMETHING THAT WE WILL BE BUILDING INTO THE EVALUATION OVER THE NEXT THREE YEARS. >> WELL ACCRUAL IS AICAL THEANCH EVERYBODY FACES BUT JUST TO POINT OUT IT LOOKS LIKE YOU'RE ONLY LOOKING LIKE AT THE ACCRUAL OF HALF WHAT HAVE THEY REALLY ACCRUE. YOU'RE ALLOWING A LOT OF LEEWAY, IT I THINK IT SUGGESTS MORE FEASIBILITY STUDIES BEFORE THE STUDIES ARE EVER PLACED AND INSTEAD OF GOING BACKWARDS AND TRYING TO FIX IT, I THINK YOU WILL FIND PROBLEMS ARE VERY SIMILAR AND COULD BE IDENTIFIED UPFRONT AND WOULD IDENTIFY STUDIES THAT IF THEY CAN'T BE FIXED AT THAT POINT, JUST SHOULDN'T BE DONE. >> AND WE ARE WORKING WITH THAT ON THE PHASE TRIALS SO THE DECEMBER MEETING THAT DR. MOONY MENTION SIDE HOW DO WE APPROACH THINGS VERY, VERY EARLY AS IN PREDEVELOPMENT. I THINK AS WELL, PERCY HAS A NEW PROGRAM SO WE'RE LOOKING AT A SIMILAR APPROACH FOR ETCTN. >> CHRIS? >> I WANT TO GIVE FEEDBACK TO JEFF AND PERCY, SO THANK YOU FOR PRESENTATIONS, IT'S MUCH CLEARY WHAT WIEWR DOING THERE AND I THINK IT'S A TERRIFIC IDEA BECAUSE WHAT YOU'RE DOING IS YOU'RE CREATING A PROJECT TEAM TO MANAGE A SERIES OF STUDIES AND IT'S VERY ANALOGOUS TO WHAT WE HAVE AN INDUSTRY COMPOUND DEVELOPMENT TEAM THAT IS RESPONSIBILITY FOR THE COMPOUND BUT OVERSEEING A NUMBER OF DIFFERENT STUDIES AND I PRESUME THAT THIS GROUP HAS INSIGHT INTO WHAT THE COMPANY IS DOG OR NOT DOING SO THE SCIENTIFIC GAPS WOULD COME VERY APPARENT AND THEN CAN YOU STEP IN AND FILL THEM. SO THAT'S IN THE OLD SYSTEM IT WAS ONLY THE INVESTIGATION DRUG BRANCH SCIENTIST THAT SORT OF HAD THE OVERVIEW OF ALL THE STUDIES WITH THE COMPOUND AND THEN WOULD HAVE TO MAKE THE SORT OF STRATEGIC BECISIONS SO THIS NEW SYSTEM I THINK IS TERRIFIC. >> SO EXCELLENT PRESENTATION, SO IF YOU HAVE--WE CAN EVALUATE ARE THE PATIENTS REFLECTIVE OF THE POPULATION OF THE UNITED STATES OR DOES IT VARY AMONG REGIONS, ET CETERA? >> THAT'S A GOOD QUESTION. NOT FOR THIS ANALYSIS BUT ANOTHER ONE OF THOSE PIECES OF DATA WE'RE ABLE TO COLLECT NOW WITH THE ECTCN SYSTEM. >> OKAY, THANK YOU. >> SO I HAD A MORE GLOBAL QUESTION FOR ALL THE SPEAKERS IS TO WHAT EXTENT IS THERE CROSS FERTILIZATION BETWEEN THE ECTCN AND THE ETN, SO I'M THINKING THOSE ACCRUAL TOOLS LOOK HELPFUL FOR ALL ACCRUAL TRIALS AND I WAS THINKING BACK TO THE PRESENTATION THAT THE BIOMARKER WORK AND IMAGING BIOMARKER WORK THAT GOES ON IN EACH SET OF TRIALS SHOULD INFORM EACH OTHER SO IS THERE EFFORTS FOR SHARING THESE VALUABLE TOOLS BETWEEN THOSE DIFFERENT NETWORKS. >> I CAN SPEAK TO THE TOOLS ON THAT BUT WE DO WITH NCTN IN THE PROCESS OF BUILDING A REPERTOIRE OF TOOLS TO USE AND WORKING WITH PERCY WE WILL SEE HOW WE CAN TAIL LORA RODRIGUEZ THOSE, SO IT'S REAL IMPORTANT FOR US TO MAKE SURE THAT BOTH NETWORKS HAVE--HAVE THE SAME ACCESS TO TOOLS. BECAUSE WE THINK THEY'LL CROSS OVER. >> AND THEN ALSO I MIGHT ASK YOU ABOUT THE BIOMARKERS AND IMAGING PIECE, SO THERE'S COMMONNALLITY BETWEEN GROUPS THAT EXPAND BIOMARKER IMAGING TECHNIQUE AND THE CENTERS AND HOW ARE THESE NETWORKING HELPING EACH OTHER WITH THAT. >> WE'RE USUALLY IN A STAGE OF BIOMARKER DEVELOPMENT OR VALIDATION AND WHAT WE HAD DONE IS TO CONSIDER IF I HAVE OF ALL WITH BIOMARKERS, I THINK IT IS DIRECTIONALLY ARE TAKING IT, BUT TO MOVE MORE TO A HUB BASED OR REFERENCE LAB IF YOU WILL RATHER THAN HAVING MULTIPLE LABS DOG THE SAME THING BECAUSE THAT'S--ONE MORE EFFICIENT, NUMBER TWO HAVE YOU A BETTER QAQC MECHANISM FOR BIOMARKERS, THE SAME CAN BE SAID FOR IMAGING SO IF IT IS TRULY AN INVESTIGATIONAL IMAGING TECHNIQUE THEN WE WILL HAVE TO IN ADVANCE IDENTIFY CENTERS THAT ARE ABLE TO ACTUALLY DO THAT PARTICULAR INVESTIGATIONAL IMAGING ANALYSIS AND OUR GOAL IS REALLY TO POINT THINGS SO TAT THINGS ARE READY TO MOVE INTO PHASE THREE OR LATERRIFIES TRAILS SO TO WORK OUT ALL THE BULGES IN THE SYSTEM OR THE ISSUES, IDENTIFY THE PROBLEMS WITH PESMEN COLLECTION OR ANALYSIS AND THOSE KINDS OF THINGS. SO I WOULD DESCRIBE IT AS A GROUND WORK OF A BASELINE WITH THE KINDS OF THINGS WE WANT TO DO. >> IN PARTICULAR, WE PRESENTED FROM OR AKRON, A PHASE TWO STUDY OF FLT OF THE 71 TRIALS SO AS I SAW IN THIS YOUR PROPOSAL, IT WOULD BE A SHAME TO HAVE TO REINVENT THAT WHEEL, ALL OF THE CALIBRATION ACCRUAL AND ANALYSIS TOOLS SO THE NETWORKS WOULD BENEFIT IN A LOT OF WAYS TO INFORM EACH OTHER. >> FINAL COMMENT, SUSAN DID YOU RAISE YOUR HAND? >> I DIDN'T KNOW IF THERE WAS TIME. VERY INTERESTING AND EXCITING CHALLENGING THINGS. I WONDERED WHAT THE ROLE OF INDUSTRY ACTUALLY SI SUSPECT IT'S PROBABLY VARYING WITH DIFFERENT COMPANIES IN THESE GROUPS AND THE OTHER QUESTION, ONE OF THE CHALLENGES WE'VE HAD HERE AND IN INDUSTRY, ALSO IS THE AVAILABILITY OF THESE BIOMARKERS ADEQUATELY CHARACTERIZE ET CETERA OR THE PREAL DATA AND I WONDER HOW YOU ARE MANAGING, HOW WERE FINDING SOME OF THESE ISSUES AND IT SOUNDED LIKE YOU HAD PRETTY CHALLENGING PRECLINICAL PROGRAMS, I WONDERED HOW IT'S FUNDED AND ORGANIZED AND I REALIZE I'M ASKING A LOT WHEN YOU HAVE NO TIME. >> WELL, I COULD AT LEAST INITIALLY ADDRESS HOW WE WORK WITH INDUSTRY AND WE WORK CLOSELY WITH INDUSTRY AND WE WORK WITHIN THE SCOPE OF OUR CREDA AGREEMENTS AND WE MAKE SURE WE'RE DEFINING NONOVERLAPPING DEVELOPMENT PLANS AND PLANS THAT WILL HELP FACILITATE THE DRUG DEVELOPMENT AND IN OUR CLANICAL TRIALS AND THEY CAN BE TRANSLATE INTOED INDUSTRY AND WE HAVE SEVERAL EXAMPLES OF THAT WHERE I THINK THAT HAS WORKED VERY WELL. WITH REGARD TO FUNDING THAT IS A SLIGHTLY MORE COMPLICATED QUESTION, BUT WITHIN WITH THE CONTEXT OF THE PHASE ONE GRANTS THERE IS FUNDING WITHIN THE GRANT SO BIOMARKER DEVELOPMENT BUT MORE SPECIFICALLY THERE IS FUNDING TO OBTAIN THE BIOPSY IN THE CONTEXT OF CLINICAL TRIAL AND THAT IS A RELATIVELY LARGE EXPENSE IN THE CONTEXT OF TRIALS AND THEN AFTER THAT, WE PUT DIFFERENT THINGS TOGETHER, SO WE MAY GET FUNDING FROM INDUSTRY, WE MAY GET ADDITIONAL BIOMARKER FUNDING FROM PROGRAMS THAT HAVE PUT TOGETHER THINGS LIKE THIS SO THAT WE CAN LEVERAGE A VARIETY OF DIFFERENT ASSETS. >> THANK YOU SO, JUST TO FINISH UP WE'RE ALWAYS LOOKING FOR ADDITIONAL AGENDA ITEMS SO IF THERE ARE UNANSWERED QUESTIONS OR ADDITIONAL ITEMS WE WOULD LIKE TO PUT SOME PRESENTATIONS OR SPECIFIC DISCUSSIONS ON TO SUBSEQUENT AGENDA PLEASE SEND THOSE IDEAS, QUESTIONS, ISSUES TO SHEILA AND I. THE ONLY BIT OF NEW BUSINESS AND I'LL HOPE IT UP FOR A SECOND TO MAKE SURE THERE'S NO OTHER ITEMS PEOPLE WANT TO DISCUSS BEWE WILL BE WORKING ON SETTING UP OR DEVELOPING A WORKING GROUP TO FURTHER DISCUSS OPPORTUNITIES FOR INTRAMURAL EXTRAMURAL COLLABORATIONS WITH NCI, SHEILA AND I WILL WORK WITH THAT AND BRING IDEAS BACK TO CTAC. ARE THERE ANY OTHER ITEMS THAT PEOPLE WANT TO BRING UP? IF NOT, THANK YOUAL FOR ATTENDING AND YOUR INPUT AND WE WILL SEE YOU IN MARCH!