>> SO LET'S TAKE OUR SEATS AND WE'LL GET STARTED. A COUPLE OF STANDARD ITEMS TO GO THROUGH. FIRST I WOULD LIKE THE WELCOME EVERYBODY TO 15th MEETING OF CTAC. THIS IS OUR OPPORTUNITY TO PROVIDE FEEDBACK, COMMENTS AND IDEAS TO THE NCI AND I HOPE PEOPLE WILL TAKE ADVANTAGE OF THAT TODAY AS WE GO THROUGH THE AGENDA. SO WE HAVE NEW MEMBERS THAT I WOULD LIKE TO WELCOME. WE HAVE A LIST OF PEOPLE THAT HAVE JOINED US FOR THIS MEETING. INCLUDING NANCY DAVIDSON WHO IS DIRECTOR OF THE CANCER CENTER AT THE UNIVERSITY OF PITTSBURG. NANCY IS FORMER PRESIDENT OF ASCO AND IS WELL KNOWN TO OUR COMMUNITY. DR. PHILLIP KEEBLER, PRINCIPLE INVESTIGATOR AT THE COLUMBUS CCOC. WELCOME. MARY MCCAIB, DIRECTOR OF THE CANCER SURVIVORSHIP PROGRAM AT MEMORIAL SLOAN-KETTERING. WELCOME. MIGUEL (INAUDIBLE) PROFESSOR OF ONCOLOGY, OHIO STATE, PHASE 1 DRUG DEVELOPMENT AND I THINK LUNG CANCER AS WELL. AND GEORGE WEANER, CANCER CENTER DIRECTOR, UNIVERSITY OF IOWA, COMPREHENSIVE CANCER CENTER IN IOWA CITY. WE ALSO HAVE A NUMBER OF ADDITIONAL, FIVE ADDITIONAL PEOPLE GOING THROUGH THE PROCESS OF APPROVAL FOR THE COMMITTEE. I'LL JUST MENTION THEIR NAMES BRIEFLY. SUSAN BRAWN, KEVIN COULD LYNN, DIRECTOR OF THE UNIVERSITY OF MARYLAND CANCER CENTER, GEORGE SLEDGE, IMMEDIATE PAST PRESIDENT OF ASCO AND PROFESSOR AT INDIANA UNIVERSITY CANCER CENTER. GILLIAN THOMAS, PROFESSOR OF RADIATION ONCOLOGY AT STONY BROOK, UNIVERSITY OF TORONTO. AND FRANK (INAUDIBLE) WHO IS VICE PRESIDENT FOR STRATEGIC PROGRAMS AT WAKE FOREST MEDICAL CENTER. SO WELCOME, ALL, WE HOPE THAT YOU WILL RAPIDLY PARTICIPATE IN OUR DELIBERATIONS OVER THE NEXT FEW HOURS AND IN SUBSEQUENT MEETINGS. I NEED TO READ AN OPENING STATEMENT. AS COMMITTEE MEMBERS I WANT TO REMIND YOU TO ABSENT YOURSELF DURING SPECIFIC DISCUSSIONS WHENEVER YOU'RE PARTICIPATION IN DELIBERATIONS ON A PARTICULAR PRODUCT, PROGRAM OR SPECIFIC MATTER WOULD CONSTITUTE A CONFLICT OF INTEREST OR CREATE AN APPEARANCE OF ONE. IT IS INCUMBENT UPON YOU TO ADVISE THE EXECUTIVE SECRETARY DR. PRINDIVILLE AND ABSTAIN FROM ANY PARTICIPATION IN DISCUSSION OR ACTION REGARDING THAT MATTER. IN LIGHT OF CURRENT POLICIES GOVERNING CONFLICT OF INTEREST BASED ON FINANCIAL HOLDINGS, OF A SPECIAL GOVERNMENT EMPLOYEES WHICH WE ALL ARE, WHICH INCLUDE ALL MEMBERS OF HIS COMMITTEE, WE MUST DEPEND ON YOU TO VOLUNTARILY ABSENT YOURSELF DURING ANY AND ALL DISCUSSIONS OF MATTERS THAT COULD CONCEIVABLY IMPACT THE STATUS OF THOSE HOLDINGS. WE TRUST YOUR JUDGMENT IN THESE INSTANCES. BY LAW, A QUORUM OF BOARD MEMBERS IS REQUIRED FOR EACH INSTANCE WHICH A VOTE OCCURS IN AN OPEN SESSION. DURING THIS MEETING NINE APPOINTED MEMBERS MUST BE PRESENT TO VOICE VOTES. THE NCI ADVISORY BOARD ARE NOT VOTING UNTIL CLEARED BY THE NCI ETHICS OFFICE. I THINK ALL OUR NEW MEMBERS ARE CLEARED. NO, THEY'RE NOT. THEY KNOW WHO THEY ARE. THANK YOU. OKAY. ALSO NEED TO TAKE A LOOK AT YOUR CONFLICT OF INTEREST STATEMENTS, THEY'RE IN THESE PURPLE FOLDERS AND SIGN THOSE AND PASS THEM TO DR. PRINDIVILLE WHEN YOU GET A MOMENT. GOING TO READ NOW THE PUBLIC COMMENT STATEMENT, MEMBERS OF THE PUBLIC WHO MAY WISH TO EXPRESS VIEWS REGARDING ANY ITEMS DISCUSSED DURING THIS MEETING MAY DO SO IN WRITING. BY WRITING DR. SHEE WILL PRINDIVILLE, EXECUTIVE SECRETARY WITHIN TEN DAYS OF THE MEETING, ANY WRITTEN STATEMENTS BY MEMBERS OF THE PUBLIC WILL RECEIVE CAREFUL CONSIDERATION. FOR YOUR SO YOU'RE AWARE THIS MEETING IS BEING VIDEOCAST TO THE PUBLIC BY THE NIH VIDEOCAST WEBSITE AND THE VIDEOCAST IS ALSO ARCHIVED SO PEOPLE CAN VIEW IT AT LATER TIME. I WOULD LIKE TO NOW TURN ATTENTION TO ANY COMMENTS ON THE JULY 2011 MEETINGS, ANY CORRECTIONS OR COMMENTS THAT PEOPLE MAY HAVE REGARDING THE MINUTES?Jjs IF THERE ARE NONE I WILL ASK FOR A MOTION TO APPROVE THE MINUTES FROM JULY 2ND. ALL IN FAVOR. OPPOSED. ANY ABSTENTIONS. MINUTES ARE APPROVED. WE WILL NOW TURN TO THE NCI UPDATE GIVEN BY DR. JAMES DOROSHOW WHO IS GOING TO BRING US UP TO DATE ON SOME OF THE CURRENT NCI ACTIVITIES ONGOING SINCE OUR LAST MEETING. >> THANKS, JIM, THIS IS I WANT TO MAKE VERY CLEAR THIS IS AN EXTRAORDINARILY PEAL IMITATION OF DR. VARMUS WHICH NO ONE CAN ACTUALLY DO APPROPRIATELY BUT I WILL DO MY VERY BEST. I'M NOT GOING TO TAKE OFF MY TIE, HOWEVER, TO DO THAT. OKAY. SO THE THINGS THAT HAROLD -- CATHY USUALLY CATHY. BUT IN ANY CASE, LET ME GO THROUGH SOME OF THE THINGS THAT HAROLD WENT THROUGH FOR THE BOARD OF SCIENTIFIC ADVISERS ON MONDAY, ONES OF INTEREST TO EVERYONE SO EVERYONE BUDGET SO POINTS TO BE MADE ABOUT 2011 THAT CLOSED THE END OF SEPTEMBER, WAS THAT ROUGHLY IT WAS 1106 RO1s WERE FUNDED, DOWN ABOUT 100 GRANTS FROM 2010 FISCAL YEAR. TO DO THAT THE MONEY BECAUSE THE NCI AND THE NIH GOT FOR THE FIRST TIME IN HAROLD'S MEMORY THE NIH HAD NEVER GOTTEN AN ACTUAL ABSOLUTE REDUCTION. SO THE 1% REDUCTION WAS REFLECTED IN NOT ONLY DECREASE IN OUR ONE FUNDING BUT ALSO CUT FROM 1 TO 5% ACROSS ALL THE DIVISIONS AND PROGRAMS FOR 2011. I'M SURE THAT LORI CAN COMMENT BUT THESE TTD TOOK A $25 MILLION CUT, THE 5% REDUCTION IN ITS BASE BUDGET. SO THE QUESTION IS WHAT WILL GO FORWARD. YOU ALL KNOW THERE'S A CONTINUING RESOLUTION THAT IS IN EFFECT UNTIL THE 18th OF THIS MONTH, WHICH YOU MAY NOT KNOW THE CONTINUING RESOLUTION ACTUALLY HAS A 1.5% DECREASE IN THE AMOUNT OF MONEY FOR THE NIH THAT IS BUILT INTO IT AND WHETHER THAT WILL BE THE ENDING NUMBER FOR 2012, NOBODY KNOWS. THE SENATE HAS A 1% DECREASE IN ITS BILL THAT'S NOT BEEN MARKED UP AND A 3% INCREASE BUT SO MANY CONTINGENCIES ASSOCIATED WITH IT BUT IT'S VERY UNLIKELY TO ACTUALLY BE -- TO GO FORWARD. SO THE TRUTH IS THAT NO ONE UNDERSTANDS EXACTLY WHERE WE'LL BE OTHER THAN IT'S VERY LIKELY THAT NOT ONLY THE NIH BUT THE NCI WILL BE DOWN PERHAPS NOT AS MUCH AS 2011 BUT DOWN THEN THE REAL CONCERN IS WHAT WILL HAPPEN FOR 2013. JUST SO EVERYONE KNOWS WE HAVE A LONG MEETING, THE END OF THE SUMMER TO PLAN FOR THE DIREST CONTINGENCIES FOR 2013. THROUGH AN EXERCISE WHAT WOULD IT LOOK LIKE TO TAKE A MAJOR REDUCTION, 20, 25% CUT OVER A COUPLE OF YEARS AND TRY TO FIGURE OUT WHAT WOULD HAPPEN. JUST I THINK I CAN CONVEY THIS, THIS IS NOT A SECRET, LAST YEAR A LOT OF PROGRAMS GOT ACROSS THE BOARD CUTS, 5% CUT, EVERYBODY TOOK A CUT. I THINK THE OPPORTUNITY FOR DEALING WITH THE -- ESPECIALLY THE 2013 BUDGET WILL BE DIFFERENT. THERE'S A REAL COMMITMENT TO LOOK AT BIG PROGRAMS AND RATHER THAN TO DO MORE ACROSS THE BOARD 1, 2, 3% CUTS, HAVE TO LOOK AT MAJOR PROGRAMS THAT COULD BE ELIMINATED. NOT A FUN THING TO CONSIDER. OTHER ISSUES THAT WE'RE DIS-- THAT WERE DISCUSSED. DR. HARLOW WILL TALK PROVOCATIVE QUESTIONS EXERCISE WHICH IS VERY INTERESTING, I WOULD LOVE TO HEAR FROM EVERYONE AT THE VARIOUS CENTERS. THIS IS A PRETTY FAIRLY MODEST RFA, THE AMOUNT OF MONEY IS ONLY ABOUT $15 MILLION SET ASIDE, THAT DOESN'T MEAN THAT THERE COULDN'T BE MORE MONEY THAT'S PAID OUT. IF A LOT OF REALLY FANTASTIC GRANTS COME IN. BUT THE IDEA IS IF YOU HAVE GONE TO THE WEBSITE TO THAT GENERATED THE QUESTIONS COME FROM THE EXTRAMURAL COMMUNITY AND MY UNDERSTANDING IS THAT THERE HAVE BEEN OVER 700 LETTERS OF INTENT SUBMITTED FOR THOSE PROVOCATIVE QUESTIONS ACROSS ALL THE QUESTIONS I DON'T KNOW HOW MANY GRANTS WILL COME IN BUT IT COULD BE MORE THAN THAT. IT'S A VERY INTERESTING EXERCISEh<+ AND YOU'LL HEAR ABOUT IT. ED WILL DO A GREAT JOB TALKING ABOUT IT THIS AFTERNOON. ONE THING YOU MIGHT THINK ABOUT AS HE GOES THROUGH THAT, IT'S NOT ALL BASIC AND TRANSLATIONAL RELATED BUT IT'S MOSTLY TO THINK ABOUT HOW SUCH EXERCISE EITHER EXACTLY IN THAT VEIN OR IN A BROADER VAIN ACROSS THE TRANSLATIONAL ARENA MIGHT BE SOMETHING OF INTEREST TO THE TREAX MURAL COMMUNITY, HOW WOULD YOU THINK ABOUT DEVELOPING THE TOPICS, HOW DO YOU ENHANCE TEAM SCIENCE, ARE THERE WAYS TO DO THAT WITHIN THE CONTEXT OF THE NUMBER OF GRANTS THAT ARE GOING TO GET FUNDED WITHIN THE NCI BASE. A THIRD THING HE TALKED ABOUT WHICH I'M SURE EVERYONE IN THE COMMITTEE IS INTERESTED IN IS THE DRUG SHORTAGE. AND THE EXECUTIVE ORDER PRESIDENT OBAMA PUT OUT TEN DAYS AGO. AND YOU ALL KNOW THAT THOSE ARE IMPORTANT THINGS THAT WILL I THINK HELP THE FDA DO SOME OF ITS JOBS BETTER BUT IT'S NOT GOING TO -- THE EXECUTIVE ORDER IS NOT GOING TO TAKE CARE OF THE PROBLEM PER SE. I WANTED TO -- DIDN'T GET A LOT OF PUBLICITY, THE FDA PUT OUT A VERY INTERESTING REPORT ON THEIR RESPONSE TO THE DRUG SHORTAGE BUT ALSO THERE IS A REPORT THAT WAS PUT OUT BY THE DEPARTMENT OF HHS, BY SHERRY GLEE'S OFFICE THAT TALKS ABOUT THE OFFICE OF PROGRAM EVALUATION, SO CALLED OPE. BUT IT'S AN ECONOMIC ANALYSIS, A VERY INTERESTING ONE AND THIS MIGHT PROVOKE FURTHER DISCUSSION ONE OF THE POSSIBILITIES SHE RAISED AND ECONOMISTS RAISED WAS HOW -- BECAUSE EVERYBODY -- I THINK EVERYBODY BELIEVED UNLESS ADDITIONAL INCENTIVES TO THE PRODUCERS IT WILL BE DIFFERENT TO GET TO MORE INJECTABLE GENERICS TO PRODUCE SO THE QUESTION IS WHETHER OR NOT THE PURCHASING GROUPS THAT ARE SO -- HAVE SUCH A STRONG ROLE IN THIS ARENA, WHETHER OR NOT THE CONTRACTING ACTIVITIES OF THOSE GROUPS MIGHT BE RETHOUGHT TO INCENTIVIZE THE APPROPRIATE COMPANIES TO HAVE SOME KIND OF AN INCREASE IN WHAT THEY CHARGE SO THAT THERE COULD BE SOME KIND OF A SUPPLY, NOT JUST A ONE WEEK OR TWO WEEK SUPPLY OF THOSE AGENTS. SOMEONE HAS TO PAY FOR IT. AND THE QUESTION IS HOW TO PROVIDE THE INCENTIVES TO MAKE THAT HAPPEN. I THINK THAT'S VERY IMPORTANT. IT MAYBE SOMETHING THAT THIS COMMITTEE WANTS TO HEAR MORE ABOUT, TALK ABOUT IN MORE DETAIL, BUT IT IS SOMETHING THAT BOTH DR. VARMUS AND I HAVE BEEN VERY DEEPLY INVOLVED IN DISCUSSIONS WITH THE ASSISTANT SECRETARY FOR HEALTH, IT'S REALLY A GREAT IMPORTANCE. FOURTH THING, THIS IS NOT -- ANY IDEA R-21 ANNOUNCEMENTS GO OUT FOR THE -- (OFF MIC) >> SO THIS IS VERY IMPORTANT AND I HOPE YOU TAKE THIS BACK TO YOUR COLLEAGUES. AFTER A LOT OF DISCUSSION, A LOT OF WORK BY DR. GRAY'S OFFICE, THE NCI LEADERSHIP HAS DECIDED TO BASICALLY PUT TOGETHER AN NCI-WIDE ANNOUNCEMENT FOR R-21s. SO WHAT THIS MEANS IS THAT THE 30, 40, 60, HOW MANY? HOW MANY PAs DID WE HAVE? WE HAD 20 DIFFERENT PROGRAM ANNOUNCEMENTS BECAUSE THE NCI HAD NEVER AGREED TO ACCEPT R-21 GRANTS IN AN UNSOLICITED FASHION WITHOUT A SPECIFIC PROGRAM ANNOUNCEMENT OR AREA THAT FOCUS. MANY NOT ALL BUT MANY OF THE OTHER INSTITUTES EXCEPT NOT ONLY RO-1 INITIATED BUT INVESTIGATOR INITIATED R-21 GRANT AND AFTER DISCUSSION WHAT WILL GO OUT IN JANUARY, FEBRUARY IS AN ANNOUNCEMENT THAT NCI WILL ACCEPT R-21s ON ANY SUBJECT THAT ANY INVESTIGATOR WANTS TO PROPOSE WHETHER IT'S A CLINICAL TRIAL, IT'S A PRELIMINARY SET OF TRANSLATIONAL STUDIES, WHATEVER IT IS, I THINK THIS ONE IS A BIG IMPROVEMENT, PAULETTE IS TRYING TO WORK HER MAGIC SO THESE GRANTS ARE REVIEWED BY NCI STUDY SECTION WHICH WILL BE A GREAT HELP AND I THINK IT WILL HELP THE CLINICAL TRIALS COMMITTEE, IT WILL HELP THE TRANSLATIONAL RESEARCH COMMITTEE BECAUSE IT WON'T MEAN YOU HAVE TO FIT WHAT YOU'RE DOING INTO A SERIES OF NARROW BOXES. I THINK IT WILL BE HELPFUL, THE PAY LINE IS DIFFICULT BUT THAT'S ONE AREA THAT WILL I THINK BROADEN THE ABILITY TO APPLY FOR THOSE KINDS OF GRANTS. LAST COUPLE OF THINGS I WANT TO TALK ABOUT, I THINK WE HAVE SLIDES FOR -- OKAY. JUST TO REMIND, SOME OF YOU KNOW ABOUT THIS, PERHAPS NOT SO MUCH, IS A ACTIVITY CALLED FOR IN THE CLINICAL TRIALS WORKING GROUP REPORT, THE CLINICAL INVESTIGATOR TEAM LEADERSHIP AWARDS AND SHEILA PRINDIVILLE AND CCCT HAVE BEEN IN CHARGE OF PUTTING TOGETHER AND DEVELOPING THE APPLICATION PROCESS FOR THESE AWARDS WHICH ARE SPECIFICALLY FOCUSED ON RECOGNIZING INVESTIGATORS WHO DO NOT HAVE THEIR OWN SOURCE OF FUNDING, NOT RO-1 PIs OR ANY FORM OF PISHIP ON AN NIH OR NCI GRANT BUT ACTUALLY ARE THOSE INDIVIDUAL WHOSE AT YOUR INSTITUTION THE CRITICAL INDIVIDUALS PUT PATIENTS ON FILE GET SAMPLES TOGETHER FOR YOUR SPORES AND BY AND LARGE DON'T GET A LOT OF RECOGNITION, WE HAVE GONE THROUGH THREE YEARS OF APPLICATIONS. THESE AWARDS ARE FOR $50,000 A YEAR FOR TWO YEARS. THE IDEA BEING THAT AS MUCH THE RECOGNITION AS THE MONEY BUT AT LEAST TO FREE UP PERHAPS A DAY A WEEK OF THE INDIVIDUAL TIME TO CONTINUE TO ADVANCE THEIR CAREER. BECAUSE THEY'RE ESSENTIAL AND THEY GET RECRUITED AWAY BY PRIVATE PRACTICE ALL THE TIME. THIS IS A LIST OF 2011 INVESTIGATORS, THEY COME FROM ALL OVER THE COUNTRY. IN FACT, THE RULES ARE SPECIFICALLY STIPULATED THAT NO ONE CANCER SENOR AT ANY ONE TIME CAN CAN HAVE MORE THAN ONE INDIVIDUAL SUPPORTED IN THIS WAY. I CAN TELL YOU PART OF MY JOB LOOK AT THESE APPLICATIONS WHICH ARE PUT TOGETHER NOT ONLY BY THE INDIVIDUALS BUT BY THE CANCER SENOR DIRECTORS WHO SUPPORT THE INDIVIDUALS THESE ARE REMARKABLY ACCOMPLISHED, SENIOR ASSOCIATE PROFESSORS AN JIEWB YOUR ASSOCIATE PROFESSOR -- JUNIOR ASSOCIATE PROFESSORS WHO IT'S OBVIOUS DO THINGS FOR THEIR INSTITUTION AND THEIR CANCER CENTER, THEIR HOSPITAL THAT ARE ESSENTIAL TO THE CLINICAL RESEARCH MISSION. SO MY ONLY THING -- WE WILL DO A FORMAL EVALUATION AND HOPEFULLY WE'LL TELL YOU IN THE NEXT YEAR OR TWO WE STIMULATED THEIR ABILITY TO STAY IN ACADEMIA HAVING DONE THE REVIEWS FOR THE PAST THREE YEARS, SUCH A SMART AMOUNT OF MONEY, IF THERE'S ANYTHING I CAN DO TO P P DOUBLE THE NUMBER OF INDIVIDUALS BECAUSE THERE'S TWICE AS MANY INDIVIDUALS TO GET NOMINATED ON A YEARLY BASIS WHO DESERVE THIS RECOGNITION, I WOULD DO SO. BUT I THINK THAT BEST WE CAN DO IS COME BACK AND PROVIDE, HERE ARE THE INDIVIDUALS, HERE IS WHAT THEY ARE FUNDED TO DO, HERE IS WHAT THEY HAVE DONE, I THINK YOU'LL BE IMPRESSED AND IT'S A SMALL THING WE CAN DO TO HELP THE CLINICAL RESEARCH EFFORT. LAST THING I'M GOING TO COVER IS JUST TO -- IS AN FYI TO MAKE SURE Y'ALL KNOW ABOUT THIS. THIS IS ALSO AN INITIATIVE THAT WAS STARTED A COUPLE OF YEARS AGO THAT WAS CALLED FOR IN THE CTWG REPORT. BASICALLY TO TRY TO PROVIDE RESOURCES FOR INDIVIDUALS WHO NEED SUPPORT FOR MULTI-SITE TRIALS THAT MAY NOT BE THE KIND OF THING EASILY DONE OR COULD EASILY BE DONE IN THE COOPERATIVE GROUPS. FRANKLY I HOPE IN THE FUTURE THERE'S NOT A NEED FOR THIS ACTIVITY GOING FORWARD. BUT IN THE INTERIM THERE WERE MANY AND HAVE BEEN MANY INSTANCES WHICH SPORE INVESTIGATORS WANTED TO COME TOGETHER TO DO A 100 PATIENT TRIAL, RANDOMIZED PHASE 2, ET CETERA AND THEY HAD NO WAY TO DEVELOP THE STATISTICAL DATA MANAGEMENT SUPPORT FOR THESE TRIALS AND CERTAINLY HAD NO WAY TO DEVELOP CAPITATION SUPPORT FOR THE ACTUAL COLLECTION OF DATA. SO OVER THE PAST YEAR AND A HALF OR SO, TWO YEARS, YEAR AND A HALF? ABOUT A LITTLE MORE THAN A YEAR, WE HAVE HAD FOUR SUBMISSIONS THAT HAVE COME IN FROM INVESTIGATORS, AGAIN, IT COULD BE INVESTIGATORS IN CANCER CENTERS OR OTHER INVESTIGATORS TO HAVE PROPOSALS THAT GO TO ONE OF THE STEERING COMMITTEES IF THEY APPROVE THOSE FROM POSALS THEN WE PROVIDE SUPPORT FOR THESE TYPES OF TRIALS. WE HAVE MADE A FEW MINOR TWEAKS TO WHAT WILL BE ELIGIBLE FOR 2012. BUT AS YOU SEE, THE REAL FOCUS, I THINK THE WAY IT'S BEEN USEFUL CURRENTLY IS THE AREA OF RARE DISEASES. AND THIS IS HELPED BRING TOGETHER INDIVIDUALS WHERE THERE'S REALLY ACTUALLY NO WAY TO DO THIS NOW IN THE GROUPS. BUT INDIVIDUALS WHO HAVE ACCESS TO PATIENT POOLS OF VERY UNUSUAL DISEASES, BUT THERE'S OPPORTUNITY TO MAKE SUBSTANTIVE PROCESS AND WE HAVE BEEN ABLE TO SUPPORT. THIS BUT GOING FORWARD I HOPE THIS IS AN ACTIVITY THAT WITH THE REORGANIZATION OF THE GROUPS REALLY THIS EFFORT WILL BECOME MOOT AND UNNECESSARY. APPRECIATE YOUR TIME AND HAPPY TO TAKE QUESTIONS IF I CAN. WE HAVE TIME FOR QUESTIONS. HEARING NONE, I HATE TO PUT DR. PASSER ON THE SPOT BUT WONDER WITH THE DRUG SHORTAGE ISSUE IS A COMPLEXION ONE, JIM MENTIONED IN HIS COMMENTS WHETHER RICK -- THE RESPONSE TO THE PROBLEM AND THOUGHTS ABOUT IS THERE SOMETHING THIS COMMITTEE COULD DO TO HELP AT ALL AND JUST MORE UNDERSTANDING I GUESS OF THE ISSUE. >> THIS IS HANDLED BY A DIFFERENCE PART OF THE FDA AND NOT ONCOLOGY OFFICE, THIS IS SEGREGATED INTO A TEAM THAT HANDLES DRUG SHORTAGES. AS SUCH THE ONCOLOGY OFFICE THAT U SUPERVISE REALLY IS DISTINCT FROM WHAT'S GOING ON HERE. I HAVE HAD ACCORDANCES WITH THEM AND THIS HAS BEEN A LONG STANDING PROBLEM WITH A LOT OF DIFFERENT ISSUES ASSOCIATED WITH THEM SOME ECONOMICS, SOME SECONDARY TO ECONOMIC ISSUES IN A SENSE THAT MANY DRUG COMPANIES ARE NOT PROFITABLE DRUGS, REALLY DON'T PUT A LOT OF RESOURCES INTO MANUFACTURING AND KEEPING MANUFACTURING TECHNIQUES, ET CETERA, TO A MINIMUM STANDARD. WHICH GENERALLY WOULD NOT OCCUR IN MORE PROFITABLE DRUG SITUATION. I PERSONALLY, HERE AGAIN, THIS IS MY PERSONAL FEELING, IF ONE WANTS TO ADDRESS THESE ISSUES, IF LEGISLATION OR SOME OTHER ISSUES COME UP, IT WOULD BE MUCH BETTER TO WORK ON ISSUES OF INCENTIVES RATHER THAN SOME TYPE OF PUNITIVE MECHANISM. BRUCE CHAVNER CALLED ME AT REQUEST OF HAROLD AND THIS WAS MY COMMENT TO HIM, WE DEALT WITH TRYING TO DO PUNITIVE THINGS TO DRUG COMPANIES FOR MANY, MANY YEARS AT THE FDA AND WHAT THIS RESULTS IN IS A LARGE AMOUNT OF LITIGATION THAT STEMS FROM PUNITIVE MEASURES AND PEOPLE TRYING TO FIGURE OUT WAYS OF GETTING AROUND IT. ONCE YOU INSTITUTE INCENTIVES TO MAKE THEM WANT TO DO AND IMPROVE MANUFACTURING TECHNIQUES, THEN PEOPLE GENERALLY TEND TO CLAMOR TO DO THESE THINGS RATHER THAN TRYING TO FIGURE OUT HOW TO GET AROUND THEM. IT'S A COMPLICATED THING, WE HAVE A WHOLE TEAM, WE RECEIVED ADDITIONAL RESOURCES TO IMPLEMENT THIS TEAM TO LOOK AT DRUG SHORTAGES INCLUDING EARLIER NOTIFICATIONS, WHEN THESE WOULD OCCUR, LOOKING AT SIZE OF DRUGS WHEN THE DRUG SHORTAGES ARE NOTED. IT IS A VERY COMPLICATED ISSUE MULTIPLE BASES HERE. ADDITIONAL QUESTIONS, NANCY? >> ONE OF THE QUESTIONS I HAVE ON THE DRUG SHORTAGE IS CLEARLY CONGRESS HAS TO DO SOMETHING. I MEAN, IT FALLS IN THEIR COURT. AND I GUESS THIS IS A QUESTION FOR EVERYBODY AROUND THE TABLE. IS THERE ANY SENSE THAT THEY'RE MOVING TOWARDS A CONSTRUCTIVE SOLUTION? [LAUGHTER] >> AS A FEDERAL -- CONGRESS ALWAYS MOVES (INAUDIBLE) (INDISCERNIBLE). >> THIS IS SOMETHING THAT THE ADVOCACY COMMUNITY IS PAYING A LOT OF ATTENTION TO. >> AS THEY SHOULD. >> YES. WE'RE WORKING VERY HARD WITH A VARIETY OF COALITIONS THAT ARE TRYING TO PUSH CONGRESS IN THE DIRECTION OF A CONSTRUCTIVE SOLUTION. SO FAR WE HAVEN'T SEEN A LOT OF MOVEMENT IN THAT AREIN AND WONDERING IF ANYBODY ELSE HAS. I'M NOT SEEING ANY NODS. OKAY. THANK YOU. >> SO THIS IS ALSO A QUESTION FOR YOU, RICK. I THINK THE SOLUTIONS BEING DISCUSSED ARE COMPLEX AND INCENTIVE ALSO TAKE A WHILE TO INSTITUTE. DO YOU HAVE A SENSE OF WHAT THE LIKELIHOOD OR IS THERE REASONABLE LIKELIHOOD WE AS A NATION WILL RUN OUT OF ONE OR MORE OF THESE LIFE-THREATENING DRUGS THROUGH THE UPCOMING YEAR? LIFE-SAVING DRUGS IN THE UPCOMING YEAR? I DON'T HAVE ANY KNOWLEDGE OF ANY IMPENDING DISASTER SO TO SPEAK. IT'S HARD FOR ME TO HAVE A CRYSTAL BALL ON THIS. AS I STATED, I THINK BOTH THE DRUG COMPANIES THAT ARE MANUFACTURING THESE DRUGS ARE REALLY IN A SPOTLIGHT, SO TO SPEAK, AS WELL AS THE FDA IS IN A SPOTLIGHT TO REALLY ADDRESS THIS PROBLEM IN A SHORT-TERM BASIS UNTIL LONG-TERM SOLUTIONS ARE LOOKED AT. SO SOME OF THESE SOLUTIONS WOULD INCLUDE WHEN WE DO HAVE EARLIER NOTIFICATION TO LOOK AT FOREIGN OUTSOURCING IN BRINGING THE BRUGS OUT FROM CANADA, EUROPE, AND ALSO HAVING SOME FLEXIBILITY IN THE INSPECTIONS AND WHAT WE ALLOW AND WHAT WE DON'T ALLOW. HOWEVER, THERE ARE SOME ISSUES THAT HAVE TO BE ADDRESSED. WE CAN'T ALLOW DRUGS TO GO ON THE MARKET THAT ARE CONTAMINATED BY BACTERIA OR ANYTHING LIKE THAT. THERE'S BASIC STANDARDS COMPANIES HAVE TO MEET. I THINK WHAT THE SPOTLIGHT AND WITH ENOUGH NOTIFICATION, I WOULD HOPE THAT THERE WOULD NOT BE A SERIOUS DRUG SHORTAGE THAT IMPACTS SIGNIFICANTLY LIFE-SAVING THERAPIES. AGAIN, I DON'T HAVE A CRYSTAL BALL. >> I UNDERSTAND THAT AND THE HOPE IS THAT STRATEGY APPLIES. THE QUESTION FOR US PERHAPS IS WHAT WILL WE DO WHEN WE'RE OUT? >> LET ME ASK YOU AND MONICA AND OTHERS, BECAUSE WE'RE TRYING TO GET A HANDLE ON IMPACT OF THE -- THIS WEEK IT'S THIS AND NEXT WEEK SOMETHING ELSE. BUT IN OVERALL THE IMPACT OF WHAT YOU SEE AND THE SHORTAGE ACCRUAL AND THE CANCER SENORS AND THE GROUP. I WOULD LIKE TO GET FOR THE RECORD SOME ESTIMATES, IF YOU DON'T MIND. >> AND IT'S A DIFFICULT NUMBER BECAUSE WE DONE TRACK PATIENT WHOSE DON'T GO ON WE HAVE OPERATIONAL RULES IN PLACE FOR CTEP AS FAR AS THE AMOUNT OF DRUG ON HAND TO GET A PATIENT STARTED ON A PROTOCOL. THE PROTOCOL REQUIRES DOXORUBICIN TOMORROW AND WE DONE HAVE IT WE WON'T ENROLL. SO WE WILL MONITOR TRENDS AND DECREASE ACCRUAL AND THAT COULD POTENTIALLY INFER WHAT IT IS BUT WE DONE HAVE A SYSTEM IN PLACE TO ACTUALLY DETERMINE THAT. DO WE HAVE MULTIPLE ANECDOTAL STORY? ABSOLUTELY. WE HAVE PATIENTS NOT GETTING ENROLLED, IT'S REGIONAL AT TIMES BUT WE CLEARLY THINGS ARE NOT GETTING ENROLLED. AS FAR AS WHAT PERCENTAGE THAT IS, THAT'S A DIFFICULT NUMBER TO COME BY RIGHT NOW. >> WHAT WE'RE SEEING IS A THIRD OF STUDIES NOW ARE AFFECTED IN ONE WAY OR ANOTHER IT IS DOING ONE THING THAT'S FAIRLY PROFOUND, I THINK WE ALREADY SEE, NEW STUDIES COMINGEN BOARD ARE STUDIES THAT WE HAVE BUT SITES HAVEN'T PUT THROUGH IRB AND STARTED UP. IF THERE'S A DRUG ON THAT LIST WHY BOTHER PUTTING IT ON IRB. WE'RE SEEING SITES NOT COME ON BOARD AS A RESULT OF THIS. FOR MANY ONGOING STUDIES WHERE PEOPLE HAVEN'T COME ON YET AND WE'RE ALSO OBVIOUSLY TALKING ABOUT NEW STUDIES THINKING MAYBE NOT OPENING THEM DEPENDING ON WHAT HAPPENED SO I THINK THE DOWNSTREAM EFFECT OF THAT LIKE MOST OF THESE UNCERTAINTIES IS PROFOUND BECAUSE IT'S JUST PUTS SUCH A DELAY AND SUCH A LASTING AFFECT EVEN IF THE DRUG WERE SUDDENLY IN AMPLE SUPPLY TOMORROW. >> IN OUR INSTITUTION WE%3o HAD QUITE A BIT OF DEBATE ON THIS AND THIS CAME ACROSS WITH PACLA TAXOL IN PARTICULAR. OUR INITIAL KNEE JERK REACTION WAS TO PRIORITIZE THE PATIENTS IN THE UNDERLYING CLINICAL TRIALS BUT A GROUP, REALLY QUESTION THAT BECAUSE SOME CLINICAL TRIALS USING A (INAUDIBLE) SETTING AND YOU HAVE PATIENTS YIEWGING IN A CARE SETTING SO YOU CAN'T PRIORITIZE CLINICAL TRIALS BOTH PATIENTS THAT CAN BE CURE. NOW EVERY PATIENT HAVE TO GO ON IT YOU NEED TO COME UP WITH A WHY AND ET CETERA. SO IT'S NOT AN EASY SOLUTION, YOU CANNOT JUST SAY YOU'RE GOING TO USE ALL THE TAXOL YOU HAVE FOR CLINICAL TRIALS. >> FROM A NARROW PERSPECTIVE, THERE IS A TRIAL FOR TREATMENT FOR METASTATIC COLORECTAL CANCER GOING AND GOING AND GOING. IT'S ALMOST DONE. AND SHORTAGE, WE HAVE NO IDEA WHEN IT'S GOING TO BE DONE. IT'S SO CLOSE. BUT THE 5 FU PEOPLE JUST DONE KNOW WHEN. >> OUR CCOP SHUT DOWN TRIALS LAST MONTH BECAUSE WE DIDN'T HAVE ENOUGH 5 FU AND WHEN WE GOT SOME WE OPENED THE ADJUVANT TRIALS BUT WE'RE OPEN FOR BOTH BUT IT COMES AN GOES EVERY MONTH. >> ONE OTHER CONCERN IS ISSUE OF PROTOCOL VIOLATIONS, FOR SOMEONE ON STUDY AND YOU CAN GET THE DRUG WHEN THEY'RE DUE. AND HOW TO DEAL WITH THAT, REALLY IS -- COULD RESULT IN SOME VERY CONFUSING DATA AT THE OTHER END IF THERE'S PATIENT WHOSE DIDN'T GET THE THERAPY AS PRESCRIBED. >> I WONDER WHETHER THE SMALLER INSTITUTIONS AND IN PARTICULAR MINORITY SERVING INSTITUTIONS MAYBE ADVERSELY AFFECTED MORE SO THAN THE CANCER CENTERS LIKE MINE THAT HAVE MORE WEIGHT IN PURCHASING POWER AND CONTINUE TO GET SOME OF THESE DRUGS WHILE THOSE THAT DON'T ARE WITHOUT SO SOME OF YOUR CLINICAL TRIALS ACCRUE TO THOSE VERY IMPORTANT COMMUNITY GROUPS MAYBE ACTUALLY QUITE ADVERSELY AFFECTED. >> ANY OTHER QUESTIONS FOR JIM? I HAVE ONE. I DON'T MEAN TO PUT YOU ON THE SPOT AND I DON'T KNOW IF YOU CAN ANSWER THIS QUESTION. >> YOU NEVER MEAN TO PUT ME ON THE SPOT. [LAUGHTER] >> YOU MENTIONED ABOUT MORE SIGNIFICANT CUTS AS A POSSIBILITY, AS THE BUDGETS ARE FURTHER DECREASED. I WONDER -- I THINK AS A SORT OF RESEARCH COMMUNITY, WE HEAR ABOUT VARIOUS PROGRAMS BEING LOOKED AT FOR THEIR PRODUCTIVITY OVER THE YEARS, CERTAINLY THE SPORE PROGRAM IN PARTICULAR HAS COME UNDER SOME EVALUATION IN THIS REGARD. CAN YOU GIVE US A SENSE AS TO WHICH PROGRAMS OR HOW NCI IS APPROACHING THIS SHOULD THERE HAVE TO BE MORE SIGNIFICANT CUTS? HOW YOU MIGHT SEE THIS PLAYING OUT IF IT NEEDS TO BE? >> NO DECISIONS HAVE BEEN MADE ALONG THOSE LINES. TO LOOK AT EVERY PROGRAM THAT IS COMING UP, IF IT'S AN RFA AND IT'S A FIVE YEAR CYCLE FOR COMPETITIVE RENEWAL. AND LOOKING VERY HARD AT EACH AND EVERY PROGRAM ACROSS THE ENTIRE SPECTRUM IN THE INSTITUTE. TO SEE WHETHER OR NOT THE INVESTMENT, THE TOTAL INVESTMENT OR THE INVESTMENT OUGHT TO BE DECREASED, JUST HOW IMPORTANT THAT PARTICULAR PROGRAM IS, VERSUS ALL THE OTHERS. I THINK THAT BASICALLY ESPECIALLY IN THIS COMING YEAR BECAUSE WE DON'T KNOW WHAT THE COMMITTEE IS GOING TO DO OR NOT DO. THAT IT WOULD BE -- IT IS INCOUPLE BENEFIT UPON US TO LOOK CAREFULLY AT ALL THE RFAs THAT COME THROUGH IN 2012, WHICH ACTUALLY CALL FOR MONEYS TO BE -- BEGUN TO BE RESPENT IN 2013. THE GENERAL PERSPECTIVE, WE TAKE A VERY TOUGH LOOK AT EVERY PROGRAM THAT IS UP FOR COMPETITIVE REVIEW, THAT WOULD BE REFUNDED IN 2013. >> ONE CLARIFYING QUESTION THERE. PRE-CLINICAL AND CLINICAL, ACROSS THE BOARD. GOOD. CAN YOU REMIND US OF WHICH THE BIG PROGRAMS WOULD BE THAT FALL UNDER THAT, EVERYONE THAT COMES UP FOR RENEWAL NEXT YEAR? >> UNFORTUNATELY MY OTHER COLLEAGUES AND DIVISION DIRECTORS ARE NOT HERE. I CAN'T TELL YOU OFF THE TOP OF MY HEAD HOW MANY PROGRAMS IN DIVISION OF CANCER BIOLOGY ARE ACTUALLY UP TO BE RECOMPETED IN 2013, 2014. BUT I GIVE AN EXAMPLE OF A VERY IMPORTANT PROGRAM THAT WILL MAKE DR. ABRAMS WHENCE BUT THE PHASE 1 PROGRAM IS UP FOR RECOMPETITION IN 2013. I HAVE NO DOUBT THAT WHEN WE GO THROUGH THE PROCESS OF TRYING TO RE-EVALUATE THAT PROGRAM, A VERY TOUGH EYE, EVEN SOMETHING THAT HAS BEEN TRADITIONALLY VERY PRODUCTIVE WILL BE SCRUTINIZED. THERE ARE MANY OTHER RFAs EVERY YEAR ANYWHERE FROM 50 TO $70 MILLION A YEAR WORTH OF RENEWED RFA PROGRAMS THAT COME UP FOR -- I JUST DONE HAVE A LIST IN FRONT OF ME BUT IT IS NANCY, A VERY BROAD SPECTRUM FOR THINGS THAT ARE VERY BASIC TO CLINICAL TRIALS. >> SO HERE IS A QUESTION, THE CLINICAL TEAM LEADERSHIP AWARD, IT'S AN EXCELLENT IDEA. I CONGRATULATE YOU FOR THAT. ANY PLANS OR POSSIBILITY OF RELAXING SO ONE INSTITUTION CAN HAVE MORE TWHAWN INVESTIGATOR AT A TIME? -- MORE THAN ONE INVESTIGATOR AT A TIME? >> THAT WAS A STRONG RECOMMENDATION WHEN THE PROGRAM WAS INITIATED BECAUSE WE REALLY DON'T WANT TO -- THERE ARE OUTSTANDING INDIVIDUAL SMALL CANCER SENT ERGS AND LARGE CANCER SENORS. MANY LARGE CANCER CENTERS MAY HAVE A BIGGER POOL TO CHOOSE FROM AND WE REALLY WOULD LIKE TO MAKE SURE THAT THE SMALL AMOUNT OF MONEYS THAT EXIST ARE AVAILABLE ACROSS THE SPECTRUM OF INSTITUTION. IT WOULD BE EASY TO MAKE THIS AN APPLICATION THAT WAS FILLED WITH INDIVIDUALS FROM -- I WON'T USE W GEOGRAPHIC LOCALE BUT IT COULD GET DISTORTED QUICKLY. I THINK THAT THOUGHT WAS TO TRY VERY HARD TO MAKE SURE THAT INDIVIDUALS GET SUPPORTED ACROSS THE COUNTRY. >> YOU AND JIM BOTH MENTIONED THE SPORE PROGRAM, WE KNOW THAT'S UNDERGOING, COMPLETED THE REVIEW, PROCESS. DO YOU HAVE A SENSE OF WHAT THE TIMETABLE ON A DECISION? A LOT OF COMMENTS ABOUT THAT PROGRAM. >> THERE HASN'T BEEN A FORMAL REVIEW OF THE SPORE PROGRAM. >> IS IT -- I CAN'T REMEMBER WHAT IT STANDS FOR, HAVE DONE FORMAL REVIEWS TO GENERATE A REPORT TO DR. VARMUS I UNDERSTAND AND WE WHEN THROUGH THAT. AND HAD THE IMPRESSION THAT THAT WAS GOING TO LEAD TO A REVIEW. >> WHAT HASN'T HAPPENED IS WHETHER OR NOT THERE WILL BE A REVIEW THAT BOARD OF SCIENTIFIC ADVISERS DOES ON ANY PARTICULAR PROGRAM AS THEY DID FOR THE CaBIG PROGRAM. NO DECISION HAS BEEN MADE WHETHER TO DO THAT OR NOT TO DO THAT FOR ANY ONE PROGRAM OTHER THAN caBIG THAT'S ALREADY GONE THROUGH THAT. >> DO YOU HAVE DO YOU KNOW HOW MANY SPORE INTERVIEWS TAKING PLACE, WHERE IS THAT INFORMATION GOING? >> THAT WILL GET PRESENTED TO THE SCIENTIFIC PROGRAM LEADERSHIP COMMITTEE, DR. (INAUDIBLE) WILL PRESENT THAT EVALUATION IN THE NEXT COUPLE OF MONTHS. THAT'S A SO-CALLED PROGRAM EVALUATION IS NOT AN OUTSIDE EVALUATION OF THE PROGRAM. IT'S WHOLE -- BY A BOARD. SO REALLY TWO DIFFERENT LEVELS OF REVIEW. >> ANY ADDITIONAL QUESTIONS? IF NOT, THANK YOU VERY MUCH. I THINK WE'RE A LITTLE BIT AHEAD OF TIME. WE CAN GO AHEAD AND GET STARTED SO SUSAN ERICKSON WHO HAS COME BEFORE THE COMMITTEE MANY TIMES TO UPDATE US ON LEGISLATIVE ACTIVITIES OR LACK THEREOF AT TIMES AND UPDATE US HOPEFULLY SHE'LL BE ABLE TO SHED LIGHT ON WHAT'S GOING ON, MAYBE HELP WITH NANCY'S QUESTION FROM EARLIER THIS MORNING. >> THANK YOU. THANK YOU, MEMBERS OF THE BOARD FOR THE OPPORTUNITY TO REPORT ON LEGISLATIVE ACTIVITIES THIS MORNING. SO I'LL START TALKING ABOUT APPROPRIATIONS. I WOULD LIKE TO TELL YOU AB INTERACTIONS THAT NCI STAFF HAS HAD WITH CONGRESS TO SHOW YOU WE'RE DOING OUR JOBS HERE, MAKING SURE CONGRESS WREBS WHO WE ARE AND WHAT WE'RE DOING. THE TOPIC IS THE DRUG SHORTAGE ISSUE SO THERE IS SOME LEGISLATIVE ACTIVITY AND I WILL BE TALKING ABOUT THAT. SO APPROPRIATIONS, NO APPROPRIATION BILL HAS PASSED YET. FISCAL YEAR DID END SEPTEMBER 30th AND THE NEW ONE BEGAN SO IN ORDER TO KEEP RUNNING THE CONGRESS PASSED A CONTINUING RESOLUTION THAT WILL EXPIRE ON NOVEMBER 18th. SO HOW DID WE GET HERE? WHY DID THAT HAPPEN? LOT OF REASONS BUT THE ONES I'LL TALK ABOUT ARE -- THE APPROPRIATIONS COMMITTEE DO MOST OF THEIR WORK ON THE INDIVIDUAL APPROPRIATIONS BILL, SORT OF IN THE APRIL, MAY, JUNE, JULY TIME FRAME AIMING TO PASS THEM BY THE END OF SEPTEMBER. THIS YEAR A LOT OF THAT TIME WAS REALLY TAKEN UP WITH THE DEBT CEILING NEGOTIATIONS AND THAT DELAY PROGRESS IS PRETTY MUCH SORT OF STOPPED PROGRESS ON MOST OF THE OTHER THINGS GOING ON. SO TOWARDS THE END OF SEPTEMBER, THE ACTIVITY DID PICK UP. AND THE LABOR HHS EDUCATION BILL PASSED INCENTIVE OHIO IN SENATE, NOT FULL SENATE BUT BY APPROPRIATIONS COMMITTEE SEPTEMBER 21st, THE HOW LABOR HHS BILL WAS NOT ACTUALLY FORMALLY INTRODUCED OR ACTED ON BY THE ECONOMY BUT IT WAS MADE -- COMMITTEE BUT IT WAS MADE PUBLIC SEPTEMBER 29th BY THE CHAIRMAN OF THE COMMITTEE AND I'LL TALK MORE ABOUT THAT, IT WAS KIND OF AN UNUSUAL WAY TO DO THINGS. SO WE'LL START WITH THE SENATE. WHAT ELSE HAPPENED IN THE SENATE OTHER THAN THE BILL GETTING INTRODUCED? WELL, SENATOR MORAN, REPUBLICAN FROM CONGRESS OFFERED AN AMENDMENT, THE END OF THE DEBATE ON THE BILL TO INCREASE NIH FUNDING BY $190 MILLION. THAT WAS CERTAINLY GOOD NEWS FOR US. THE BAD NEWS WAS THAT THE NIH INCREASE WAS GOING TO BE PAID FOR BY AN ACROSS THE BOARD CUT TO THE REST OF THE BILL WHICH MADE IT PRETTY MUCH UNACCEPTABLE TO MOST OF THE MEMBERS. BUT SENATOR MORAN, I WILL BE TALKING ABOUT HIM MORE LATER. HE'S LOOKING LIKE HE WOULD REALLY LIKE TO BE SOMEBODY, A STRONG SUPPORTER OF THE NIH AND PARTICULARLY NCI I THINK. SO SO SOME OTHER THINGS HAPPENED IN THE HOUSE. THE BILL THAT CHAIRMAN REEBERG POSTED ON HIS WEBSITE, INCLUDED HIGHER FUNDING LEVELS FOR NIH AND NCI THAN THE SENATE HAD INCLUDED. AND THAT WAS THE GOOD NEWS. BUT THE BAD NEWS WAS THAT THERE WERE ALSO PROVISIONS IN THIS BILL THAT PROHIBITED FUNDING FOR THE IMPLEMENTATION OF HEALTHCARE REFORM WHICH PRETTY MUCH WAS A POISSON PILL FOR THE DEMOCRATS. THEY WON'T BE ABLE TO VOTE TO PASS THAT BILL. THE MINORITY LED BY RANKING MEMBER ROSE DELARO OBJECTED THE WAY IT WAS HANDLED. THE MINORITY MEMBERS OF THE SUBCOMMITTEE HAVE NO INPUT WHATSOEVER AND CONGRESSWOMAN DELORES SAID THE CHAIRMAN IS NOT THE SUBCOMMITTEE. SO SHE DIDN'T WANT TO BE ASSOCIATED WITH THAT BILL. THE END RESULT OF THAT IS THE BILL IS UNLIKELY -- THIS PARTICULAR BILL IS UNLIKELY TO BE VOTED ON. SO WHAT'S NEXT? WHERE DO WE GO FROM HERE? THE HOUSE AND SENATE LEADERSHIP NEEDED A STRATEGY TO MOVE THESE BILLS. MANY OF THE LAST FEW YEARS ALL THE APPROPRIATION BILLS HAVE MOVED THROUGH AN OMNIBUS BILL WHERE ALMOST ALL APPROPRIATION BILLS WERE PUT INTO ONE PACKAGE, IT ALLOWS VERY LITTLE TIME FOR DEBATE ON INDIVIDUAL ISSUES AN PRETTY MUCH THE LEADERSHIP REACHED AN AGREEMENT, WHAT WILL BE IN THE ONMIBUS BILL AND MOVED FORWARD FOR THE VOTE. THEY RECEIVED A LOT OF CRITICISM FOR THIS PARTICULAR PROCESS SO THIS YEAR THEY WERE LOOKING FOR A WAY TO CUT THE TIME THAT IT WOULD TAKE TO PASS ALL THE APPROPRIATIONS BILLS BUT STILL AVOID A SINGLE CATCH-ALL BILL. SO THE AGREEMENT WAS TO HAVE A SENATE COMBINE TWO OR MORE BILLS TO SMALLER PACKAGES AND NOT OMNIBUS BUT A MINI BUS. THEY'RE THE FIRST MINI BUS HAS BEEN WORKED ON OVER THE LAST COUPLE OF WEEKS AND IS EXPECTED TO BE VOTED ON TOMORROW. THIS INCLUDED THREE BILLS THE LABOR H BILL WAS NOT ONE OF THOSE. IF THE MINI BUS, THE FIRST MINI BUS PASSES, REALLY, THIS IS SORT OF A TRIAL TO SEE HOW THIS IS GOING TO WORK, IT WOULD NEED TO BE PASSED BY THE HOUSE AND SIGNED BY THE PRESIDENT. SO WHAT HAPPENED THE LAST WEEK IS A CONFERENCE COMMITTEE WAS APPOINTED THAT INCLUDED SUBCOMMITTEES FROM -- MEMBERS FROM THE THREE SUBCOMMITTEES WHOSE BILL WAS INCLUDED. HOUSE AND SENATE BILLS AND THAT IS WHAT NOW THAT CONFERENCE BILL IS NOW WHAT WILL COME UP FOR A VOTE IN THE SENATE TOMORROW. THERE'S A SECOND MINI BUS BEING TALKED ABOUT THAT WILL START TO BE WORKED ON NEXT WEEK. ONE THING SEEMS FOR SURE IS THE LABOR HHS EDUCATION BILL WILL PROBABLY BE IN THE LAST GROUP. IT COULD BE THE VERY LAST BILL, SENATOR HARKEN SAID I THINK YESTERDAY HE IS A CHAIRMAN OF THE SUBCOMMITTEE. WE'RE USUALLY THE CABOOSE IN THIS TRAIN. SO IN THIS FIRST MINI BUS THERE'S LIKELY A PROVISION THAT WILL BE A NEW CR THAT WILL EXTEND THROUGH MID DECEMBER. SO WHEN THAT PASSED THEN WE'LL HAVE THAT EXTRA TIME THAT CONGRESS WILL HAVE TO WORK ON THE BILL. LEAVING THAT REL TUFLY DOWN-BEAT TOPIC I THOUGHT I WOULD TALK ABOUT NCI INTERACTION WITH CONGRESS. AND WE HAVE HAD NCI STAFF GO DOWN TO INFORM CONGRESS ABOUT MANY OF THE ACTIVITIES THAT WE'RE ENGAGED IN. THE TOPIC OF CANCER RESEARCH WAS COVERED BY DR. VARMUS IN LATE SEPTEMBER. THE AACR INVITED MEMBERS OF THE REPUBLICAN STUDY COMMITTEE TO HEAR FROM DR. VARMUS ON THIS TOPIC. THE REPUBLICAN STUDY COMMITTEE IF YOU'RE NOT FAMILIAR IS A SUBSET OF HALF MEMBERS WHO ARE GENERALLY REGARDED AS LITTLE OVER TO THE RIGHT. SO THIS WAS A GREAT OPPORTUNITY TO MAKE SURE THAT THIS GROUP HEARD ABOUT GOOD THINGS THAT WE'RE DOING HERE AT NCI. OVARIAN CANCER WAS THE TOPIC THAT MANY MEMBERS WERE INTERESTED IN, THE OVARIAN CANCER NATIONAL ALLIANCE SPONSORED A BRIEFING. SEVERAL MEMBERS ATTENDED AND MANY MORE STAFF. THE DCEG'S DR. JENNIFER LOUD WENT AND SPOKE ABOUT OVARIAN CANCER RESEARCH PROGRAMS. THE INTERNATIONAL MYELOMA FOUNDATION IN OCTOBER SPONSORED ANOTHER EVENT AND THEY INVITED DR. OLA LANGREN, ONE OF CCR RESEARCHERS TO SPEAK ABOUT THIS TOPIC. REPRESENTATIVE CONGRESSWOMAN JACKIE SPEAR FROM CALIFORNIA PARTICIPATED IN THE BRIEFING. SHE DELIVERED OPENING REMARKS. STAYED FOR MOST OF THE BRIEFING. I'LL BE TALKING MORE ABOUT HER IN A MINUTE. RIGHT NOW, AS A MATTER OF FACT. ONE THING THERE EVERY TIME WE HAVE INTERACTION WITH CONGRESS, WHETHER IT'S STAFF OR MY OFFICE OR DR. VARMUS VISITS WITH MEMBERS OR STAFF, I'M ALWAYS EXTENDED AN INVITATION FOR PEOPLE TO COME THE CLINICAL CENTER AND COME TOP THE NIH CAMPUS AND REALLY -- COME TO THE NIH CAMPUS. THERE'S NO SUBSTITUTE FOR THAT. IT'S HARD FOR MEMBERS OF CONGRESS AND STAFF TO VISIT THE CLINICAL CENTER AND MEET WITH PATIENTS, TALK WITH RESEARCHERS, VISIT LABS AND NOT COME AWAY FEELING LIKE THIS IS SOMETHING WORTH SUPPORTING. SO SEVERAL MEMBERS HAVE TAKEN US UP ON THAT OFFER AND ONE OF THESE WAS ACCOMPLISHED FROM (INAUDIBLE). SHE CAME IN JULY, THAT WAS DR.'S HELMAN AND NABLE FROM THE CLINICAL CENTER. THEY LED A TOUR AND DISCUSSED PEDIATRIC CLINICAL TRIALS WHICH SHE WAS QUITE INTERESTED IN. DR. COLLINS ALSO HAD THE OPPORTUNITY TO MEET WITH THE CONGRESSWOMAN AND NIDDK TOOK THE CONGRESSWOMAN TO ONE OF THEIR LABS. SENATOR MORAN, ACTUALLY THE DAY AFTER HE INTRODUCED THAT AMENDMENT TO INCREASE THE NIH FUNDING, CAME OUT AND VISITED THE CLINICAL CENTER. HE ALSO MET WITH DR. COLLINS, THAT WAS THE SAME DAY DR. VARMUS WAS DOWN BRIEFING THE REPUBLICAN SU CITY COMMITTEE. HE DIDN'T MEET WITH SENATOR MORAN BUT DR. COLLINS DID AND THEY VISITED A LAB AND TOURED THE CLINIC WITH DR. HELMAN. I THINK SENATOR MORAN WAS VERY IMPRESSED WITH HIS VISIT HERE AND HAS SAID A LOT OF NICE THINGS. AGAIN, I THINK THIS IS STRENGTHENING HIS SUPPORT FOR NIH. CONGRESSIONAL STAFF AND ADVOCATES CAME OUT ON A VISIT SPONSORED BY RESEARCH AMERICA. MANY OF THE ICs PARTICIPATED AND DR. LENAHAN WITH NCI HAD THE OPPORTUNITY TO SHOW THEM HIS LAB AND TALK ABOUT HIS WORK. SO THAT WAS THE FIELDED STUFF. I WANT TO TALK A LITTLE BIT ABOUT DRUG SHORTAGE. THIS IS THE LEGISLATION INTRODUCED PRESERVING ACCESS TO LIFE SAVING MEDICATIONS ACT. IT'S A BILL INTRODUCED IN THE SENATE BACK IN FEBRUARY, INTRODUCED BY TWO DEMOCRATS, THE HOUSE BILL WAS THEN INTRODUCED IN JUNE THIS WAS A BIPARTISAN BILL INTRODUCED BY CONGRESSMAN ROONEY, A REPUBLICAN AND A DEMOCRAT. THE MAJOR FEATURES OF THIS BILL MANUFACTURERS NOTIFY FDA ABOUT THE CONTINUING DISRUPTION THAT RESULTS IN SHORTAGE. HHS WOULD NEED TO IMPLEMENT EVIDENCE BASED CRITERIA TO IDENTIFY DRUGS VULNERABLE TO DRUG SHORTAGES. THE GAO IS TO STUDY POSSIBLE CAUSES AND THEN HHS MUST REPORT TO CONGRESS. I THINK GENERALLY THIS LEGISLATION IS SEEN AS A GOOD START. I THINK THE SPONSORS OF THE LEGISLATION ARE OPEN TO DISCUSSIONS AB HOW TO STRENGTHEN THE BILL. I NE THEY CONTACTED NIH FOR TECHNICAL ASSISTANCE -- I KNOW THEY CONTACTED NIH FOR TECHNICAL ASSISTANCE SO WE'RE HOPEFUL THE HHS AGENCIES WILL BE ABLE TO WORK WITH THOSE MEMBERS AND PERHAPS BE ABLE TO STRENGTHEN THAT BILL. THERE'S BEEN A GREAT DEAL OF IN GENERAL CONGRESSIONAL INTEREST IN THIS TOPIC. THE HOUSE ENERGY COMMERCE COMMITTEE HELL A HEARING IN LATE SEPTEMBER. THE ASSISTANT SECRETARY FOR HEALTH, DR. KO TESTIFIED AND HE WAS ACCOMPANIED BY DR. KREEDER FROM FDA. SENATOR SHUMER WEIGHED IN ON THE ISSUE. HE HELD A PRESS CONFERENCE IN OCTOBER WHERE HE ASKED SEVERAL TRADE COMMISSIONS TO INVESTIGATE DISTRIBUTORS FOR PRICE GOUGING, THE GENERAL AREA CALLED THE GRAY MARKET. AND THEN CONGRESSMAN ELIJAH CUMMINGS LAUNCHED AN INVESTIGATION OF THE MARKET. HE IS THE RANKING MEMBER ON THE HOUSE OVERSIGHT GOVERNMENT REFORM COMMITTEE. HE DOESN'T HAVE THE AUTHORITY TO SCHEDULE A HEARING, HE CAN ASK THE CHAIRMAN TO BUT HE CAN MAKE INVESTIGATIONS OF THE ISSUE. SO HE REQUESTED INFORMATION FROM FIVE OF THE COMPANIES THAT HE WAS INTERESTED IN. THESE ARE COMPANIES THAT SELL DRUGS BUT DO NOT MANUFACTURE THEM OR TREAT PATIENTS. SO THEY'RE SORT OF A MIDDLEMAN. AND QUESTIONS HE ASKED WERE ASKED THESE COMPANIES TO ANSWER, HOW DO THEY OBTAIN THEIR DRUGS, HOW MUCH DO THEY PAY FOR THEM, HOW MUCH PROFIT DO THEY MAKE. SOME OF THE COMPANIES HAD RESPONDED. OTHERS HAVE NOT. IN NOVEMBER CONGRESSMAN CUMMINGS EXPRESSED SOME CONCERN THAT SOME OF THE COMPANIES WERE LACKING COOPERATION AND HE SEEMED INTENT ON INTENSIFYING EFFORTS TO TO LOOK INTO GRAY MARKET ISSUES. FOLLOW-UP, DR. DOROSHOW MENTIONED THIS BUT THE FDA RELEASE POSTED ON THEIR WEBSITE A REVIEW OF DRUG SHORTAGES AND THE HHS POSTED THEIR ISSUE BRIEFS, ECONOMIC ANALYSIS OF THE CAUSES OF DRUG SHORTAGES, ALSO AVAILABLE ON THEIR WEBSITE AND THEN ALL THESE ACTUALLY WERE RELEASED ON THE SAME DAY, OCTOBER 31st. THE PRESIDENT ISSUED HIS EXECUTIVE ORDER FOR THE FDA TO -- AMONG OTHER THINGS, USE THEIR EXISTING AUTHORITIES TO REQUIRE DRUG MANUFACTURERS TO PROVIDE ADVANCED NOTICE OF POTENTIAL SHORTAGES, EXPAND THEIR CURRENT EFFORTS TO EXPEDITE REGULATORY REVIEWS AN WORK WITH THE DEPARTMENT OF JUSTICE TO REVIEW CERTAIN BEHAVIORS BY MARKET PARTICIPANTS AND I THINK THAT GETS US A PRICE GOUGING ISSUE AS WELL. SO THAT WRAPS UP MY REPORT. IF THERE'S ANY QUESTIONS I'M HAPPY TO TRY AND ANSWER THEM. >> WE HAVE TIME FOR A FEW QUESTIONS. THAT WAS GREAT, VERY COMPREHENSIVE. NANCY. >> IS THERE ANY SENSE OF WHEN THE GAO REPORT WILL BE OUT? >> WE HAD HEARD NOVEMBER BUT NOTHING MORE DEFINITIVE THAN THAT. >> IF THERE ARE NO OTHER QUESTIONS WE'RE SCHEDULED TO TAKE A SHORT BREAK. WE HAVE A FEW EXTRA MINUTES SO WE'LL BE BACK AT 10:15. WE'LL HAVE GEOFF ABRAMS AND MEG MOONEY PRESENTING AN UPDATE OF THE NEW RFA. AND THE PLANS TO TRANSFORM THE CLINICAL TRIALS SYSTEM. THANK YOU.#)u >> WHY DON'T WE GET STARTED. IT'S 10:15. SO THE NEXT PRESENTATION IS AN UPDATE ON THE PRESENTATION OF THE RFA WHICH WAS APPROVED BY THE BSA ON MONDAY. AND THIS IS THE PROGRESS IN TRANSFORMING THE NCI CLINICAL TRIALS SYSTEM. SO THIS IS AN IMPORTANT PRESENTATION, I HOPE PEOPLE WILL TAKE SOME TIME AT THE END TO PROVIDE FEEDBACK. THIS IS THE -- WE HAVE THE FINAL TIME -- I BELIEVE THE FINAL TIME THE COMMITTEE CAN PROVIDE FEEDBACK TO THE NCI ON THE RFA. AFTER THIS IT GOES TO THE NIH. IT HAS TO BE WRITTEN, GOES INTO DEEP SORT OF -- THIS IS THE TIME TO REALLY MAKE YOUR FEELINGS KNOWN BEFORE IT GOES INTO THE WRITING PHASE. >> THANK YOU. I'M HAPPY TO BE I BELIEVE TO PRESENT THIS TODAY AND DOUBLY HAPPY BECAUSE IT WAS APPROVED BY THE BOARD OF SCIENTIFIC ADVISERS ON MONDAY. SOY EESM PRESENTING ON BEHALF OF NOT JUST THE CANCER THERAPY EVALUATION PROGRAM, BUT ALSO OUR OTHER COLLEAGUES AT THE NCI WHO ARE PART OF THIS PROGRAM AND HELPED US DEVELOP THIS RFA. INCLUDING FROM WITHIN DIVISION OF CANCER TREATMENT AND DIAGNOSE MOWSIS -- DIAGNOSIS, THE CANCER IMAGING PROGRAM AS WELL AS THE RADIATION RESEARCH PROGRAM. AND ALSO THE DIVISION OF CANCER PREVENTION, THE CCOC PROGRAM DIRECTOR. SO JUST WHAT I'LL DO BRIEFLY TODAY IS GO OVER WHAT WE PRESENTED IN A SHORTENED FORM TO THE BOARD OF SCIENTIFIC ADVISERS. FIRST PRESENTATION I'LL GET AN OVERVIEW OF THE CURRENT PROGRAM AND THE BACKGROUND RATIONALE FOR WHY WE HAVE THE NEW RFA AND THEN GO OVER THE PROGRESS THAT WE HAVE MADE ALREADY TOWARDS MOVING TOWARDS AN INTEGRATED NATIONAL NETWORK AND GO IN DEPTH THE SPECIFIC COMPONENTS OF THE RFA INCLUDING REVIEW CRITERIA, THE BUDGE PROPOSAL AS WELL. THE COOPERATIVE GROUP PROGRAM IS FUNDED OVER 50 YEARS AND IS FUND AS A STANDING PRUX FOR CLINICAL TRIALS IN TREATMENT AND ALSO IN SYMPTOM AND CANCER CONTROL PREVENTION AND SCREENING. FOR THE LAST 50 YEARS. IT INVOLVED OVER 3100 INSTITUTIONS 14,000 INVESTIGATORS AND 25,000 PATIENTS ARE ENROLLED ANNUALLY ON THE TREATMENT TRIALS ACROSS THE NATION. THE VAST MAJORITY, OVER 83% ARE ENROLLED OR DEFINITIVE PHASE 3 TRIALS. ONE NOTABLE STRENGTH IS THE BROADRATOR BRANCH BASE NOT JUST FROM NCI CANCER CENTERS BUT ALSO OTHER ACADEMIC CENTERS AND COMMUNITY HOSPITALS ACROSS THE UNITED STATES AND AS WELL AS INTERNATIONAL MEMBERS AN PRIVATE PRACTITIONERS. SO ONE OF THE BASIC QUESTIONS WE HAD TO ASK WHEN WE WERE MOVING FORWARD WITH THE NEW RFA IS WHETHER TO CONTINUE SUPPORT THROUGH PUBLIC INVESTMENT, A STANDING PUBLICLY FUNDED CLINICAL TRIALS NETWORK. AND AS YOU KNOW, THERE HAVE BEEN SEVERAL REVIEWS OVER THE PAST FIVE TO SIX YEARS LOOKING AT THE PROGRAM, THE MOST NOTABLE FROM THE INSTITUTE OF MEDICINE IN APRIL OF 2010. THE CONSENSUS FROM ALL THOSE REVIEWS WAS THAT THERE WAS A CRITICAL NEED FOR PUBLICLY FUNDED NETWORK. PARTICULARLY BECAUSE IT ADDRESSES QUESTIONS THAT MIGHT NOT BE TAKEN ON BY THE PRIVATE SECTOR BECAUSE THEY WOULDN'T BE NECESSARILY BE PRIORITIES FOR THEM AND THAT DOES INCLUDE INTEGRATING NEW AGENTS INTO STANDARD THERAPY COMBINING NOVEL AGENTS FROM DIFFERENT SPONSOR, LOOKING AT MULTI-MODALITY THERAPIES, ESPECIALLY SURGERY, RADIATION THERAPY, IP THERAPY BUT ALSO SCREENING, DIAGNOSTIC AND PREVENTION STRATEGIES. OBVIOUSLY LOOKING AND EVALUATING CLINICAL TRIALS IN RARE TUMOR TYPES INCLUDING PEDIATRIC CANCERS AND OTHER RARE TUMORS LOOKING AT THAT TIME OPTIMAL DURATION AN DOSE OF DRUGS AB OTHER MODALITIES LIKE RADIOTHERAPY AND LASTLY, EVALUATING COMPETING THERAPIES THAT HAVE ALREADY BEEN APPROVED FOR CERTAIN INDICATION. PUBLIC TRIALS ALSO ARE FOCUSED TOWARD DISEASE MANAGEMENT, THEY'VE NOT AGENT SPECIFIC NOR LIMITED BY MARKETING CONSTRAINTS AND THAT ALLOWS US TO LOOK AT ADDITIONAL IMPORTANT ANCILLARY RESEARCH QUESTIONS INCLUDING THOSE RELATED TO CORRELATIVE SCIENCE, IMAGING, QUALITY OF LIFE, SYMPTOM MANAGEMENT AND SPECIAL POPULATION. LAST CERTAINLY NOT LEAST IS THE SYSTEM ALLOWS EXTENSIVE DIRECT INVOLVEMENT OF EVERYONE IN THE ONCOLOGY COMMUNITY AND DESIGN, DEVELOPMENT AND CONDUCT OF TRIALS SO IT EXTENDS THE DEBATE ABOUT WHAT SHOULD BE DONE AND WHAT WE REALLY NEED TO LOOK AT ACROSS THE ENTIRE COMMUNITY. SO LOOK AT THE COOPERATIVE GROUP PROGRAM AND ACCOMPLISHMENTS OVER THE LAST SIX YEERKS WE LISTEDDED SOME HERE BUT BETWEEN 2005 AND 2011, THERE HAVE BEEN OVER 30 PRACTICE CHANGING CLINICAL TRIALS INCLUDING THERAPEUTIC AGENTS AND OTHER MO BALLTIES AND IN FACT FOUR OF THOSE ANNOUNCEMENTS WERE MADE IN THE FIRST SIX MONTHS OF 2011. YOU HAVE LISTED THOSE HERE. THEY ILLUSTRATE NICELY HOW A PUBLICLY FUNDED SYSTEM DOES ADDRESS QUESTIONS THAT MIGHT NOT BE TAKEN ON BY INDUSTRY. THE FIRST TWO INVOLVED SURGERY AND RADIOTHERAPY. AND BREAST CANCER, THE THIRD INVOLVES THE USE OF A GENERIC DRUG AT A PARTICULAR DOSE, HIGH DOSE METHYL TREXATE OR PEDIATRIC ALL. THE LAST IS MULTI-MODALITY THERAPY, LOOKING SHORT TERM GENERIC ANDROGEN DEPRIVATION THERAPY, THAT IMPROVED OVERALL SURVIVAL IN MEN WITH PROSTATE CANCER. IN ADDITION OVER THE SAME TIME PERIOD THERE'S OVER TEN FDA APPROVED APPLICATIONS USING ONCOLOGY AGENTS, MONOCLONAL ANTIBODIES AND SMALL MOLECULES FOR DIFFERENT INDICATIONS AN DISEASES, INCLUDED IN THAT LIST A PRIMARY INDICATION FOR PEDIATRIC AND ADULT POPULATIONS WITH T-CELL LYMPHOMA. IN ADDITION TO THAT, MANY GROUP TRIALS ALSO LOOKED AND SHOWED DEFINED CLINICAL BENEFITS FOR NEW INDICATIONS WITH GENERIC AGENTS, TWO ARE LISTED HERE AT THE BOTTOM OF THE SLIDE. ONE INCLUDES DANIRUBICIN AND DEATHAMEXINAN IN MULTIPLE MYELOMA. SO BASED ON REVIEWS FROM THE PAST AS YOU'RE ALL FAMILIAR WITH THE CLINICAL TRIALS WORKING GROUP AS WELL AS OPERATIONAL EFFICIENCY WORKING GROUP REPORT, WE ALSO RECEIVED RECOMMENDATIONS AND REVIEWS OF THE SYSTEM FROM ASCO AS WELL AS THE INSTITUTE OF MEDICINE REPORT IN APRIL OF 2010. SO OVER THE LAST 18 MONTHS THE NCI HAS UNDERGONE AN EXTENSIVE REVIEW AND PERIOD IN WHICH WE TRY TO OBTAIN AS MUCH INPUT AS WE COULD FROM ALL THE STAKEHOLDERS IN THE SYSTEM. ALL WHICH ARE LISTED HERE AROUND THE CIRCLE TO TRY TO UNDERSTAND HOW BEST TO MOVE FORWARD WITH THE RECOMMENDATIONS MADE BY THE REVIEW COMMITTEE AND ALSO OTHER STAKEHOLDERS. WE HAVE ALSO HAD PROFESSIONAL ANALYSIS BY THE SCIENCE TECHNOLOGY POLICY INSTITUTE ON THE OPERATIONAL EFFICIENCY OF THE PROGRAM AND WE'VE ALSO OBTAINED GENERAL PUBLIC INPUT THROUGH THE NCI MAILBOX AND WEBSITE. SO THE REPORT CONSENSUS GOALS THAT WERE ACTUALLY PUT OUT BY THE INSTITUTE OF MEDICINE IN TERMS OF WHAT THEY FELT THAT ANY PUBLICLY FUNDED SYSTEM WOULD NEED TO DO INTO THE FUTURE TO MEET NEW EMERGING SCIENTIFIC CHALLENGES, PARTICULARLY BECAUSE CANCER MEDICINE IS EVOLVING TO A MORE MOLECULARLY DEFINED DISCIPLINE WHERE THERE'S MORE GENETIC SUB CLASSIFICATIONS WITHIN TUMOR TYPES. AS WELL AS NEW WAYS TO BETTER DIAGNOSE -- SO THOSE ARE CONSENSUS GOALS PUT OUT BY THE INSTITUTE OF MEDICINE LISTED HERE IN RED, THEY INCLUDE OBVIOUSLY IMPROVING SPEED AND EFFICIENCY OF TRIAL DEVELOPMENT AND CONDUCT, INCORPORATING INNOVATIVE SCIENCE AND TRIAL DESIGN, IMPROVING TRIAL PRIORITIZATION AND ENSURING PARTICIPATION OF PATIENTS AND PHYSICIANS IN A PUBLIC SYSTEM SO WE HAVE MADE QUITE A BIT OF PROGRESS ON MANY OF THESE FRONTS. IN PARTICULAR IN TERMS OF IMPROVE EGG FISH SI, -- IMPROVING EFFICIENCY, WE HAVE IMPLEMENTED THE OPERATIONAL EFFICIENCY GUIDELINES AND WE HAVE INITIAL DATA ON THE FIRST 20 MONTHS AFTER IMPLEMENTATION OF THOSE GUIDELINES. WE SET OUT A VERY AGGRESSIVE GOAL OF TRYING TO REDUCE TIME LINE FOR PROTOCOL DEVELOPMENT AND ACTIVATION BY OVER 60% AND OUR INITIAL 20 MONTH EXPERIENCE SO FAR SHOWS THAT WE ARE REDUCING OUR TIME LINES BY 50%. SO WE'RE NOT QUITE AT THE TARGET THAT WE WANT TO BE AT BUT WE'RE CERTAINLY -- WE HAVE A LOT OF WORK TO DO TO GET THERE BUT WE'RE CERTAINLY MOVING IN THE RIGHT DIRECTION. IN ADDITION, WE STARTED TO ROLL OUT THE IMPLEMENTATION OF A COMMON DATA MANAGEMENT SYSTEM, META DATA THAT WILL BE IMPLEMENTED OVER THE NEXT 18 MONTHS SO THAT ALL TRIALS CONDUCTED IN THE SYSTEM WILL BE USING THE SAME REMOTE DATA CAPTURE SYSTEM. AND DATA WILL BE COLLECTED AN PATIENTS ENROLLED IN THE SAME MANNER ACROSS THE ENTIRE SYSTEM. IN TERMS OF INNOVATIVE SCIENCE WE IMPLEMENTED THE BUSINESS QUICK PROGRAM TO PUT INTEGRATED BIOMARKERS AS WELL AS OTHER INTEGRAL STUDIES INVOLVING QUALITY OF LIFE AND IMAGING INTO THESE DEFINITIVE LARGE SCALE TREATMENT TRIALS. SO OVER THE PAST THREE AND A HALF YEARS MORE THAN 13 PHASE 3 CLINICAL TRIALS HAVE MADE USE OF THAT PROGRAM WITH FUNDING IN EXCESS OF $22 MILLION. Y'ALL OBVIOUSLY WELL KNOW ABOUT THE DISEASE SPECIFIC STEER I COMMITTEESCH THOSE ARE INSTITUTED FROM 2006 TO 2011 IN JUST ABOUT EVERY DISEASE TYPE WHICH WE DO RESEARCH TO HELP PRIORITIZE LARGE SCALE PHASE 2 TRIALS AS WELL AS PHASE 3 TRIALS. WE ALSO HAVE IMPLEMENTED SLOILY ACCRUING GUIDELINES AN WILL GIVE SOON PROBABLY IN THE NEXT SIX MONTHS THE FIRST UPDATE ON THAT PROGRAM, THE PROGRAM TO HELP IDENTIFY PHASE 3 TRIALS THAT ARE NOT ACCRUING WELL SO THAT WE CAN MAKE THE APPROPRIATE MODIFICATIONS EARLY ON OR STOP THE TRIALS EARLY IF IN FACT THEY PROVE NOT TO BE FEASIBLE. LASTLY, IN TERMS OF ENSURING PARTICIPATION OF PATIENTS AND PHYSICIANS IN THE SYSTEM, WE HAVE HAD SEVERAL PILOT INITIATIVES TO TRY TO INCREASE REIMBURSEMENT, PARTICULARLY RELATED TO COMPLEX PHASE 2 AND PHASE 3 TRIAL. AND WE HAVE HAD INITIATIVES ASSESSING PHYSICIAN AN PATIENT FEEDBACK HOW TO ENHANCE ACCRUAL TO OUR TRIALS. SO AS WE MOVE FORWARD WE LOOKED AT THE WAY THE PROGRAM WAS STRUCTURED. THIS IS THE STRUCTURE OF THE PROGRAM AT THE BEGINNING OF THIS YEAR. AS YOU KNOW WE HAVE FUNDED TEN COOPERATIVE GROUPS OVER THE PAST DECADE BUT THEY WERE ALL REVIEWED, ORGANIZED, AND REALLY CONDUCTED EVALUATIONINGS OF THOSE PROGRAMS SEPARATELY FROM ONE ANOTHER. THEY REVIEWED DIFFERENT TIMES, THEY HAD DIFFERENT COMPONENTS. SO THEY WERE SOME DUPLICATION OF INFRASTRUCTURE ACROSS THE SYSTEM. WE TRIED OVER THE LAST SEVERAL YEARS TO CENTRALIZE MANY FUNCTIONS, PARTICULARLY ADMINISTRATIVE AND REGULATORY FUNCTIONS THROUGH THE CTSU AND THE NCI CENTRAL IRB FOR BOTH ADULT AND PEDIATRICS. AND TRIED TO CENTRALIZE PRIORITIZATION OF THE TRIALS THROUGH DISEASE SPECIFIC STEERING COMMITTEES. BUT WE STILL HAVE HAD A SYSTEM AND AN ORGANIZATION THAT HAD A SILOED EFFECT SO WE THOUGHT IN ORDER TO MOVE FORWARD AND MEET CHALLENGES GOING FORWARD THAT WE WOULD HAVE TO FUNDAMENTALLY CHANGE THE ORGANIZATIONAL STRUCTURE AND THE REVIEW PROCESS. SO THE RFA SETS OUT THE NEXT STEPS WE FEEL NEED TO BE TAKEN IN TRANSFORMING THE SYSTEM. SO IT IS A NEW RFA FOR AN INTEGRATED NATIONAL CLINICAL TRIALS NETWORK. NCI IS PROPOSING THROUGH THE RFA THAT WE CONSOLIDATE THE ORGANIZATIONAL STRUCTURE WITH FUNDING FOR ONE PEDIATRIC GROUP AND UP TO FOUR ADULT GROUPS. WE WILL ALSO BE CHANGES THE REVIEW CRITERIA SO THEY EMPHASIZE INTEGRATION AN COLLABORATION FOR OVERALL SCIENTIFIC ACHIEVEMENT RATHER THAN A SPECIFIC COMMITTEE BY COMMITTEE REVIEW OF EACH SCIENTIFIC COMMITTEE WITHIN THE GROUP AND IT WILL ALSO BE ORIENTED WITH REVIEW CRITERIA SPECIFICALLY FOR OPERATIONAL EFFICIENCY. AS PART OF THIS, WE ALSO FEEL IT'S FUNDAMENTAL THAT WE HAVE A NEW FUNDING MODEL THAT INCREASES PER CASE REIMBURSEMENT FOR HIGH PERFORMANCE ACADEMIC AND COMMUNITY SITES. ND I'LL EXPLAIN WHAT THAT MEANS IN A MINUTE. LASTLY WE THOUGHT IT WAS IMPORTANT TO HAVE COMPETITIVE INTEGRATED TRANSLATIONAL SCIENCE AWARDS TO BENEFIT THE ENTIRE SYSTEM AND TO REVITALIZE THE CANCER SENORS ROLE IN PARTICIPATING IN THE TRIALS MOUNTED BY THE SYSTEM. SO THE NEW STRUCTURE THAT WE'VE PROPOSED IS PRESENTED HERE, IT IS PART OF A MUCH LARGER SYSTEM AND WE WANTED TO PUT THAT IN CONTEXT THROUGH THIS ILLUSTRATION. ALL THE COMPONENTS IN DARK BLUE ARE THE RFA COMPONENTS GOING FORWARD IN FUNDING OPPORTUNITY ANNOUNCEMENTS BUT THEY FIT INTO AMOUNTS AS PREVIOUSLY STATED. OBVIOUSLY WE HAVE OTHER GRANT PROGRAMS WELL COORDINATED WITH THE PROGRAMS FUNDED UNDER THE RFA, PARTICULARLY THE DIVISION OF CANCER PREVENTION CCOP PROGRAM AND MINORITY BASED CCOP PROGRAM AND CANCER DIAGNOSIS PROGRAM, BANKING OF BIOSPECIMENS FROM THESE DEFINITIVE CLINICAL TRIALS. WE HAVE CONTRACT PROGRAMS THAT SUPPORT THE CENTRALLY ADMINISTRATIVE AND REGULATORY ASPECTS OF THE SYSTEM INCLUDING THE CTSU AND CENTRAL IRB. LASTLY WE HAVE ADVISORY COMMITTEES OBVIOUSLY THE DISEASE SPECIFIC STEERING COMMITTEE HELPS WITH PRIORITIZATION OF TRIALS, BUT ALSO PREVIOUS THROUGH PRESENTED TO Y'ALL, A SUBCOMMITTEE OF CTAC THAT LOOK AT CLINICAL TRIALS AND STRATEGIC PLANNING. SO WE HAVE BEEN ASKED MULTIPLE TIMES FOR TRANSFORMING THE CURRENT PROGRAM AND ALSO VERY SPECIFICALLY HOW WE THINK THE SYSTEM WILL HELP. WE CERTAINLY THINK THAT CONSOLIDATING INFRASTRUCTURE WILL ALLOW US TO GAIN IMPORTANT EFFICIENCIES, PARTICULARLY IN AREAS OF IT, REGULATORY AND ADMINISTRATIVE FUNCTIONS AN TISSUE RESOURCE MANAGEMENT. WE ALSO BELIEVE CONSOLIDATING IMAGING AND RADIOTHERAPY, TWO MODALITIES THAT IN PARTICULAR DO NOT HAVE OR HAVE VERY LIMITED PUBLIC SUPPORT, NOT PUBLIC SUPPORT, EXCUSE ME, PRIVATE SECTOR SUPPORT AND INDUSTRY SUPPORT WILL ALLOW US TO PROVIDE AND CONSOLIDATE THOSE CORE SERVICES FOR QA AND QC FOR CLINICAL TRIALS CONDUCTED ACROSS THE ENTIRE NETWORK. WE ALSO BELIEVE IT'S IMPORTANT TO INTEGRATE THE NEW COMPONENTS INTO TRIALS THAT PROVIDE VALUE-ADDED RESEARCH QUESTIONS, PARTICULARLY WITH RESPECT TO ADVANCED IMAGING AND TRANSLATIONAL SCIENCE AND WE THINK THAT AN INTEGRATED NATIONAL NETWORK HELP US INTEGRATE NEW AGENTS INTO TRIALS MORE RAPIDLY. IPILU MIRKSMAB ARE BEING INTEGRATED INTO TRIALS OF LUNG CANCER AND REQUIRE SCREENING OF LARGE POPULATION AN COMBINING THOSE AGENTS WITH SURGERY, RADIO THERAPY AND IMMUNOTHERAPY. SOMETHING WE DO THINK WOULD BE BETTER AND MORE QUICKLY ADDRESSED BY HAVING AN INTEGRATED NETWORK. IN ADDITION WE NEED TO E EVALUATE NEW AGENTS. EVEN COMMON DISEASES SUCH AS BREAST CANCER, THE NUMBER OF MOLECULARLY DEFINED PATIENT POPULATIONS RIN CREASING AND THERE'S A NEED FOR TRIAL PRIORITIZATION EVALUATING NEW AGENTS WITH STANDARD REGIMENS ACROSS VARIOUS SUBTYPES TO AVOID DUPLICATION AN OPTIMIZE ACCRUAL. SOMETHING WE ALSO THINK BETTER ADDRESSED BY AN INTEGRATED NATIONAL NETWORK. SO HERE IS THE ORGANIZATION. AS I SAID BEFORE, THE ONE THING I DON'T KNOW IF YOU CAN READ THEM BUT THEY'RE IN DARK BLUE ARE THE SPECIFIC COMPONENTS FUNDED UNDER THIS NEW RFA. I WILL GO OVER EACH IN A LITTLE BIT OF DETAIL TO EXPLAIN THEIR COMPONENTS AS WELL AS NEW REVIEW CRITERIA. FIRST WILL BE OBVIOUSLY THE OPERATIONS AND STATISTICAL CENTERS OF THE GROUPS WHICH WILL HAVE AN EMPHASIS ON COLLABORATION. THE SECOND WILL BE LOOKING AT NETWORK LEAD ACADEMIC PARTICIPATING SITES. WE WILL ALSO HAVE NETWORK INTEGRATED TRANSLATIONAL COMPONENTS AND LASTLY, WE'LL HAVE CORE SERVICES FOR QA AND QC OF IMAGING AND RADIOTHERAPY AS WELL AS A COLLABORATION WITH THE CANADIAN CLINICAL TRIALS NETWORK. IN TERMS OF GROUP OPERATIONS AND STATISTICAL CENTERS, OBVIOUSLY THEY PROVIDE STRATEGIC SIGN ACTIVE INC. STRATEGY AND GOALS ACROSS A BROAD RANGE OF DISEASES AND WE WILL BE LOOKING FOR ALL GROUPS TO BE OBVIOUSLY MULTI-DISEASE BASE AND MULTI-MODALITY. THEY WILL BE RESPONSIBLE FOR NETWORK ADMINISTRATION, ALTHOUGH OBVIOUS THINGS THAT WE ALL KNOW FROM CLINICAL TRIALS FROM STUDY CONCEPTION THROUGH PROTOCOL DEVELOPMENT AND ACCRUAL AS WELL AS ADHERENCE TO OPERATIONAL EFFICIENCY, AUDITING, QA QC PROTOCOL THERAPY, COORDINATING BIOSPECIMEN COLLECTION AND COMPLIANCE WITH FEDERAL REGULATORY AGENCIES. THE STATISTICAL LEADERSHIP OBVIOUSLY IS RESPONSIBLE FOR EFFECTIVE DESIGN AND TRIAL CONDUCT. AND WILL MONITOR QUALITY WITH CORRELATIVE SCIENCE. WE WILL ALSO HAVE A COMPONENT THAT WILL SUPPORT DATA MANAGEMENT AND ANALYSES FOR STUDIES OUTSIDE THE NETWORK GROUPS AS APPROPRIATE FROM INVESTIGATORS WHO BRING IDEAS FOR STUDIES THROUGH STEERING COMMITTEES THAT ARE APPROVED. FUNDAMENTALLY, WE ALSO HAVE TO RECONFIGURE THE WAY NCI AND NIH CONDUCTS EXTERNAL PEER REVIEW OF THE SYSTEM. THERE WILL BE EMPHASIS ON INCENTIVES FOR A NATIONAL SYSTEM BUT THE TRIALS ALL BUT DEFINITIVE PHASE 3 TRIALS AND MANY PHASE 2 TRIALS OPEN TO ALL QUALIFIED SITES AND SITES ABLE TO CREDIT ANY GROUP WHICH THEY BELONG. ALSO HOPE TO HAVE IN SPECIAL POPULATIONS FOR EXAMPLE YOUNG ADULTS AND ADOLESCENTS, GROUP TRIALS THAT IN SOME CASES THE CHILDREN'S ONCOLOGY GROUP AND ADULT GROUP CAN PARTICIPATE ON TOGETHER. THERE WILL BE REVIEW OF NETWORK COMPONENTS AT THE SAME TIME WITH SPECIFIC REVIEW PANELS FOR PARTICULAR NETWORK COMPONENTS IN THE PAST, EACH OF THE GROUPS WAS REVIEWED AT A DIFFERENT POINT IN TIME AND COMPLETELY SEPARATED FROM EACH OTHER. REVIEWING THEM AT THE SAME TIME WILL ALLOW THE RU RE VIEWERS TO BRING EXPERTISE LOOKING AT ACROSS THE NETWORK AND WILL ALLOW US THE MAKE BETTER FUNDING DECISIONS FOR THE ENTIRE SYSTEM. SCIENTIFIC EVALUATION WILL SHIFT AS PREF YSLY STATED TO EVALUATING GROUP ROLE IN THE NATIONAL NETWORK AND THEIR OVERALL DISEASE STRATEGY AND INNOVATION AND QUALITY AS OPPOSED TO A MORE DETAILED COMMITTEE BY COMMITTEE EVALUATION OF INDIVIDUAL DISEASE AREAS. THE REVIEW CRITERIA WILL HAVE A STRONG COMPONENT FOR EFFICIENT SAIND COLLABORATIVE MANAGEMENT, THAT WILL INCLUDE NOT COORDINATION AND COLLABORATION WITH THE OTHER NETWORK GROUP BUT WITH OTHER NCI PROGRAMS AND NCI INVESTIGATORS OUTSIDE THE GROUP. WE WILL HAVE A NEW PROGRAM FOR LEAD ACADEMIC PARTICIPATING SITES. WE HAVE HAD A U-10 PROGRAM FOR INDIVIDUAL ACADEMIC SITES THAT WERE CONNECTED WITH SPECIFIC GROUPS BUT WILL HAVE A NEW ORIENTATION. THESE WILL BE MULTIPLE PI GRANTS FOR ACADEMIC INSTITUTIONS WITH DEMONSTRATED LEADERSHIP ONE OR MORE ADULT GROUP, SUBSTANTIAL ACCRUAL AND EXCELLENT DATA QUALITY. THEY WILL PRESUMABLY BE HIGH PERFORMANCE SITES, MEETING ALL THOSE CRITERIA, THEY'RE TARGETED AT NCI COMPREHENSIVE AND CLINICAL CANCER CENTERS BUT OTHER LEADING ACADEMIC CENTERS. THE REVIEW CRITERIA WILL SET AN ACCRUAL THRESHOLD FOR THESE TRIALS FOR ACCRUAL FROM ACROSS THE NETWORK. SO THEY WON'T BE EVALUATED JUST ON ACCRUAL WITHIN SPECIFIC GROUP BUT INSTEAD ON HOW THEY ACCRUE TO ALL TRIALS WITHIN -- IN THE NETWORK. SO ALSO EVALUATED FOR EXPERTISE AND LEADERSHIP ROLES IN THE VARIOUS GROUPS OF WHICH THEY ARE MEMBERS. THERE'S FOCUS ON DATA QUALITY AND CONTRIBUTIONS TO TRANSLATIONAL SCIENCE. AND LASTLY, WE HOPE THAT THIS WILL STRENGTHEN SCIENTIFIC COLLABORATION ACROSS THE CANCER CENTER AN INSTITUTIONS AND THE ENTIRE NETWORK. WE ALSO WILL HAVE A NEW CATEGORY OF COMPONENT FOR THE NETWORK CALLED INTEGRATED TRANSLATIONAL SCIENCE AWARDS. THESE ALSO WILL BE MULTIPLE PI GRANTS AND SUPPORT PROMINENT RESEARCHERS FOR EXPERTISE AN EFFORTS INCORPORATING MOLECULAR STUDIES INTO THE NETWORK TRIALS AN ENABLE ACQUISITION OF PRELIMINARY DATA FOR FURTHER RESEARCH. THEY'LL HELP FUND LABORATORY BASED RESEARCHERS SO THEY CAN FACILITATE HAND-OFF OF EARLY PHASE CLINICAL TRIAL FINDINGS INTO LATER PHASE DEFINITIVE TRIALS. THE REVIEW CRITERIA WILL OBVIOUSLY FOCUS ON PEER REVIEW THE QUALITY OF SCIENTIFIC APPROACH. AND INTEGRATION OF THE CLINICAL SCIENCE INTO NETWORK TRIALS, HOPEFULLY WILL LEVERAGE IBD PEN DEN LIT FUNDED RESEARCHERS WITH RESOURCES TO WORK WITH GROUP CLINICAL SPECIMENS AN DATA TO BENEFIT GROUP RESEARCH AIM. WE ALSO EXPECT THAT THE RESEARCH AREAS SELECTED FOR THESE RESULTS IN A STRATEGY THAT WILL BE FUNDED ARE LIKELY TO BENEFIT TRIAL EFFORTS ACROSS THE NETWORK. LAST TWO COMPONENTS FOR RADIOTHERAPY AND CORE SERVICES, PROVIDE SCIENTIFIC LEADERSHIP FOR QA AN QC OF IMAGE DATA MANAGEMENT FOR RESEARCH TRIALS INVOLVING BOTH IMAGING AND RADIOTHERAPY, THE CRITERIA WILL FOCUS ON SCIENTIFIC LEADERSHIP AND EXPERTISE WITHIN CORE SERVICES ACROSS THE ENTIRE NETWORK INCLUDING INTEGRATED IT PLATFORMS FOR CAPTURING AN STORING DATA AND EFFICIENT PROCEDURES FOR ACCESSING SITE DATA FOR IMAGING AND RADIOTHERAPY TRIAL QUESTIONS. NCI HAS HAD A LONG HISTORY OF COLLABORATION WITH CANADIAN SITES AND WITH NON-PROFIT CANADIAN CLINICAL TRIALS ORGANIZES; THE LAST COMPONENT OF THE NEW RFA WILL BE A GRANT THAT COULD POTENTIALLY FUND A CANADIAN COLLABORATING TRIAL NETWORK. THE REVIEW KYE TIERIA WILL FOCUS ON THE ABILITY REGULATORY OVERSIGHT FOR U.S. NETWORK TRIALS CONDUCTED IN CANADA, IRRESPECTIVE OF WHICH GROUP IS LEADING THE TRIAL AN TO BE FULL PARTNERS IN ACCRUING PATIENTS TO U.S. NETWORK TRIALS. SO REALLY THIS NEW RFA WILL ACTUALLY HAVE FOUR DIFFERENT FUNDING OPPORTUNITY ANNOUNCEMENTS AND WILL FUND ANYWHERE FROM 43 TO 58 DIFFERENT GRANTS WE ESTIMATE. WE SORT OF ORGANIZED THE FOUR DIFFERENT FUNDING OPPORTUNITY ANNOUNCEMENTS BY THE EXPERTISE THAT WILL BE NEEDED TO REVIEW THEM. AS WELL AS BY THE TYPE OF FUNDING MECHANISM BEING USED. AND THE FREQUENCIES THAT NEW APPLICATIONS ARE ACCEPTED. SO YOU SEE THE FOUR DIFFERENT ONES HERE LISTED OR DEMARKED BY THE DIFFERENT COLORS, THE FIRST SET WILL BE THE OPERATIONAL COMPONENT SO THE GROUP STATISTICAL MANAGEMENT CENTERS UNDER ONE FUNDING OPPORTUNITY ANNOUNCEMENT. THE SECOND WILL BE FOR THE INTEGRATED TRANSLATIONAL SCIENCE AWARD, THIRD FOR RAID WROAR THERAPY AND IMAGING CORE SERVICES AND THE LAST FOR THE LEAD ACADEMIC PARTICIPATING SITES. SO IN ALL THE REVIEWS WE DID FUNDAMENTAL TO THE RECOMMENDATIONS FROM THE INSTITUTE OF MEDICINE, EVERYONE EMPHASIZED THE NEED TO PROVIDE INCREASED RESEARCH REIMBURSEMENT TO ENSURE CONTINUED PARTICIPATION OF SITES IN THE PUBLIC PROGRAM. THE BASE REIMBURSEMENT FOR PATIENTS IN THE PROGRAM REMAIN FIXED AT $2,000 PER PATIENT PER TREATMENT TRIAL, OVER THE PAST DECADE. IN 2006 THE ESTIMATE FOR AVERAGE INDUSTRY TRIAL WAS OVER $4,700 FOR PHASE 3 TRIALS. AND OVER $8,400 FOR PHASE 2 TRIALS WITH SOME INDUSTRY TRIALS PROVIDING $15,000 WITH MORE PATIENT FOR SUPPORT. A SERVING OF GROUP SITES FOUND OF THOSE PLANNING TO LIMIT PARTICIPATION IN THE PROGRAM 75% CITED INADEQUATE REIMBURSEMENT FOR THE DECLINE IN THEIR LEVEL OF PARTICIPATION. SO IT'S ESSENTIAL WE INCREASE REIMBURSEMENT. WE FEEL HIGH PERFORMANCE SITES AND THOSE WE DEFINE AS HAVING SIGNIFICANT ANNUAL PATIENT ACCRUAL BECAUSE THEY IN PARTICULAR HAVE INCREASED AN ADDITIONAL INFRASTRUCTURE COST DUE TO THE NUMBER OF PATIENTS THEY ACCRUE AND WHAT THEY NEED TO DO TO CONTINUE TO FOLLOW PATIENTS UP IN THAT LARGE ENROLLMENT BURDEN THAT WE PROPOSE FOR THOSE SITES TO INCREASE PER CASE REIMBURSEMENT FROM $2,000 PER PATIENT TO APPROXIMATELY $4,000. SO DOUBLING IT ESSENTIALLY. WE HAVE TO LOOK AT THE FINANCIAL ECONOMIC CLIMATE. YOU SEE THE BUDGET HISTORY FOR DIFFERENT COMPONENTS OF CURRENT PROGRAM OVER THE LAST SIX YEARS THE MAJORITY OF FUNDING WAS GROUP OPERATIONS AND STATISTICAL CENTERS, THOSE FIGURES ALSO DO INCLUDE CAPITATION FOR MAJORITY OF ACCRUAL, OVER THE LAST SIX YEARS. WHAT'S NOTABLE OBVIOUSLY IS THAT THE FUNDING HAS REMAINS ESSENTIALLY FLAT AND THAT THERE WAS A BUDGET CUT IN FISCAL YEAR 2011. OBVIOUSLY WITH LEVEL FUNDING THAT REALLY MEANS THERE HAS BEEN A DECREASE IN PURCHASING POWER THAT'S DEVOTED TO THE NETWORK OVER THE PAST DECADE. YOU SEE HERE THE COOPERATIVE OBLIGATIONS FOR THE LAST DECADE DEFLATED USING THE BIOMEDICAL RESEARCH DEVELOPMENT PRICE INDEX AND THERE OBVIOUSLY HAS BEEN A REAL DECLINE IN PURCHASING POWER FOR THE FUNDING PROVIDED. IN ORDER TO ADDRESS THAT WE DO WHAT'S ESSENTIAL TO PROVIDE INCREASED REIMBURSE P M. WE'RE PROPOSING UNDER THE NEW RFA THAT THERE BE AN INCREASE IN FUNDING OF $25.6 MILLION. 21 MILLION OF THAT GOES DIRECTLY TO SITES WHETHER DCTD FUNDED IN THE IMMUNITY TO INCREASE THE REIMBURSEMENT BY APPROXIMATELY $2,000 OR DOUBLING IT. WHETHER THE BREAKDOWN IS LISTED HERE WE DONE KNOW, IT DEPENDS ON ACCRUAL FROM THE INDIVIDUAL SITES BUT WE WOULD ANTICIPATE WE WOULD NEED TO PROVIDE SIGNIFICANT ADDITIONAL FUNDING TO DO THAT. IN ADDITION WE'RE RECOMMENDING ABOUT $4 MILLION BE SPENT FOR INCREASING FUNDING FOR INTEGRAL MARKERS, BECAUSE WE THINK IT'S ESSENTIAL TO HAVE THE CAPACITY TO DO THAT AND PUT IMPORTANT TRANSLATIONAL RESEARCH INTO THE DEFINITIVE PHASE 3 TRIAL. OVERALL THAT'S AN ADDITIONAL REQUEST FOR INCREASING THE FUNDING BY $25.6 MILLION. IN ORDER INTO CREASE FUNDING WE FEEL WE NEED TO MAKE A REDUCTION IN ACCRUAL SO BY PLANNING WHAT WE ANTICIPATE TO BE A 20% REDUCTION IN ACCRUAL, FROM 25,000 PATIENTS PER YEAR TO 20,000 PATIENTS PER YEAR WITH THE ADDITIONAL FUNDING THAT WE WOULD BE ABLE TO MEET THE GOAL OF AT LEAST INCREASING SUBSTANTIALLY FUNDING HIGH PERFORMANCE SITES WHICH WOULD ACCOUNT FOR 46% OF THE TOTAL ACCRUAL. SO OBVIOUSLY AS WE MOVE FORWARD THIS IS A CHALLENGING MISSION TO BALANCE ACCRUAL AND SCIENTIFIC PRIORITIES. IN THE LAST DECADE BY LARGE ADJUVANT TRIAL IN THE TUMOR OF THE BREAST AND GI CANCER. NEW FUNDING MODEL REALLY DOES REQUIRE THAT NETWORK GROUPS AND STEERING COMMITTEES MONITOR THE BALANCE OF TRIALS PRIORITIZED FOR DEVELOPMENT AND HELP DEVELOP THE STRATEGIC CONSENSUS ABOUT THE TRIALS WITH THOSE DEES AND MAKE SURE WE ENCOURAGE MORE TRIALS AND SIGN TOUGHIC OPPORTUNITIES -- AS SCIENTIFIC OPPORTUNITIES ARISE FOR THE NETWORK T. NEW REVIEW CRITERIA SHOULD FACILITATE MORE TRIALS WHICH MAY NOT HAVE TYPICALLY BEEN REPRESENTED AND HAVE BEEN UNDER-REPRESENTED RELATIVE TO INCIDENCE. AND THE PORTFOLIO BALANCE WILL BE MONITORED CLOSELY BY CTAC ON NEW STRATEGIC PLANNING SUBCOMMITTEE THAT JOE WILL SPEAK AB IN A FEW MINUTES TO ENSURE SCIENTIFIC OPPORTUNITIES PARTICULARLY IN LESS COMMON TUMORS ARE NOT MISSED. SO WE DO HAVE -- STILL HAVE A AGGRESSIVE TIME LINE FOR POTENTIAL IMPLEMENTATION. SO WE PASS THE FIRST TIME LINE, THE BSA CONCEPT REVIEW APPROVED ON MONDAY. WE WILL NOW BETWEEN NOVEMBER AND HOPEFULLY JULY OF 2012 BE DEVELOPING THE FUNDING OPPORTUNITY ANNOUNCEMENT AND GUIDELINES AND HAVE THOSE REVIEWED BY NCI'S DIVISION OF EXTRAMURAL ACTIVITIES AS WELL AS BY NIH. AND OUR GOAL IS TO RELEASE THE FOAs AND THE GUIDELINES IN JULY OF 2012. WE THEN ANTICIPATE WE HAVE RECEIPT OF COMPETING NEW APPLICATIONS THROUGH THE WINNER OF 2012, SOMETIME BETWEEN NOVEMBER AND FEBRUARY DEPENDING ON WHEN WE RELEASE THE FOAs. WITH REVIEW AND SUMMER OF 2013 AND THEN REVIEW BY THE NATIONAL CANCER ADVISORY BOARD IN DECEMBER OF 2013 AND ROLE OUT OF THE NEW AWARDS FOR THE NEW INTEGRATED NETWORK IN MARCH OF 2014. THIS IS FUNDAMENTAL AN NEW NETWORK AND CHANGE FROM THE WAY WE HAVE APPROACHED DOING PUBLICLY CLINICAL TRIALS IN THE PAST. WE HOPE THAT IT WILL BENEFIT RESEARCH AS WE MOVE FORWARD AND ENABLE US TO BETTER REACH THE SCIENTIFIC OPPORTUNITY. SO THANK YOU FOR YOUR ATTENTION AND GEOFF AND I WILL BE HAPPY TO ANSWER YOUR QUESTIONS ANYONE MAY HAVE. THANK YOU. >> THANK YOU, THAT WAS A GREAT PRESENTATION. OPEN THE FLOOR TO ANY QUESTIONS OR COMMENTS AT THIS POINT, NANCY. >> I HAVE A QUESTION ABOUT WHAT THE BSA SAID. WHAT WAS THE GENERAL REACTION AND WHAT WERE THE QUESTIONS THEY RAISED? >> IT WAS FAVORABLE IN THE SENSE THAT IT WAS APPROVED UNANIMOUSLY. SO -- OBVIOUSLY I'M ONLY PARAPHRASING WHAT I REMEMBER FROM MONDAY BUT CERTAINLY I THINK THAT THEY WERE PARTICULARLY APPRECIATIVE OF THE FACT THAT IT WAS STRUCTURED AS AN INTEGRATED NETWORK AND THAT INSTITUTIONS WOULD BE REWARDED FOR PARTICIPATING ACROSS THE NETWORK. THEY PARTICULARLY LIKE THE REVITALIZATION OF THE CANCER CENTER ROLES AND PARTICIPATING IN THE NETWORK. THEY FELT A LOT OF OPPORTUNITIES THAT WOULD BE HELPED BY HAVING AN INTEGRATED NETWORK. DATA SHARING, A VERY IMPORTANT COMPONENT THAT THEY BROUGHT UP AND WHICH WE WILL ALSO BE BRINGING UP THE FUNDING OPPORTUNITY ANNOUNCEMENTS AND GUIDELINE, THAT IT IS ESSENTIAL IN THESE PUBLICLY FUNDED SYSTEM TO HAVE ACCESS. PUBLIC ACCESS TO THE DATA AFTER THE PRIMARY RESEARCH RESULTS ARE AVAILABLE. THAT WE MAKE SURE THAT IT WAS IN THE PROGRAM, WE ENABLE THAT TO HAPPEN AS WIDELY AND QUICKLY AS POSSIBLE. THAT WAS ANOTHER LARGE COMPONENT. INFORMED CONSENT. LUCKILY I HAVE PEOPLE HERE TO HEAR WHAT HAPPENED ON MONDAY BUT ANOTHER WAS THEY WANTED TO MAKE SURE THAT OUR INFORMED CONSENT DOCUMENTS FOR THESE TRIALS ARE APPROPRIATE TO INFORM PATIENTS AND PARTICULARLY ABOUT USE OF TISSUE AND OTHER BIOSPECIMENS FOR POTENTIALLY NEW SCIENTIFIC OPPORTUNITIES INCLUDING GENOMIC APPLICATIONS OF USE OF THE BIOSPECIMENS AND THAT WE MAKE SURE THAT WE HAVE THOSE THINGS IN PLACE. >> I THINK THEY WANTED TO MAKE SURE THAT -- THEY REMINDED ME THAT WHEN WE'RE INTEGRATED WITH THE DIVISION OF CANCER PREVENTION, WHICH WE ARE. AND THAT WHEN WE -- THEY PARTICULARLY ASK WE MAKE THIS CHANGE IN THE PROGRAM WHAT DOES THAT MEAN FOR THE RESEARCH BASIS, THE CCOP PROGRAM AND MINORITY BASED CCOP PROGRAM AND WE ASSURED THEM THAT WE ARE APPROACHING THIS FROM THE NCI PERSPECTIVE AND ALSO THE EXTRAMURAL COMMUNITY PER PERSPECTIVE AS ONE INTEGRATED NETWORK. SO IT IS ANTICIPATED AS WE MOVE FORWARD WITH THIS RFA THE DIVISION OF CANCER PREVENTION WILL BE CHANGING THEIR RFA AS WELL TO REFLECT THE SAME CHANGES. ANOTHER THING THE SPECIALTY RESEARCH, AS I AM SURGICAL ONCOLOGIST BY BACKGROUND, I ALSO ECHOED THAT NEED BUT THEY WANTED TO MAKE SURE THAT RADIO THERAPY QUESTIONS, SURGICAL QUESTIONS, NON-MEDICAL ONCOLOGY BASED QUESTIONS STILL HAVE A STRONG ROLE WITH THE SYSTEM AND WE FELT EVERYTHING IN THE NEW RFA WILL SPORE THAT AS WELL. >> DO YOU KNOW ANYTHING ABOUT THE TIME SOMETHING THERE ARE A LOT OF COMPONENT PARTS, ARE YOU INVITING ALL THESE THINGS TO COME UNDER ONCE, SUBMITTED LEAD ACADEMIC ORGANIZATIONS AND THE COOPERATIVE GROUPS AN THESE VARIOUS PIECES OR ARE THEY STAGGERED IN SOME FASHION? >> THERE MIGHT BE A SLIGHTLY DIFFERENT RECEIPT DATE BUT THEY WON'T BE THAT DIFFERENT. WE WERE AIMING INITIALLY BUT WE'LL HAVE TO LOOK AT IT WHEN WE DISCUSS THIS WITH THE DIVISION OF EXTRAMURAL ACTIVITIES. FOR THE GENERAL PERIOD OF RECEIPT TO BE PRETTY CLOSE TOGETHER FOR ALL THE FUNDING OPPORTUNITY ANNOUNCEMENTS AND FOR THE REVIEWS AS WELL. BUT THEY WILL BE SOMEWHAT STAGGERED BECAUSE IT'S A SLIGHTLY DIFFERENT EXPERTISE FOR EACH OF THE FUNDING OPPORTUNITIES ANNOUNCEMENTS AND A SLIGHTLY DIFFERENCE REVIEW PANEL. IT WILL BE A VERY CENTRALIZED AND YES, WE ARE ANTICIPATING THAT TO BE DONE IN CLOSE PROXIMITY. >> THE EXTRAMURAL COMMUNITY YOU JUST GLUED 2012 FOR US. >> A FEW QUESTIONS, AT A TIME. I HATE GETTING QUESTIONS AND CAN'T REMEMBER WHAT THEY ARE. LET ME ADD ONE OTHER THING DAN IF YOU DONE MIND TO NANCY'S QUESTION. I WANT TO EMPHASIZE THE REVIEW APPLICATION WILL BE MUCH SHORTER AND MUP MORE STREAMLINED. SO THE REVIEW PROCESS WILL BE COMPLETELY DIFFERENT FROM WHAT IT'S BEEN IN THE PAST, AT LEAST THE COOPERATIVE GROUP PROGRAM. WE HAVE NEW NIH PAGE LIMITATIONS. SO I WANT TO EMPHASIZE THAT OUR GOAL WITHIN THIS IS TO MAKE SURE THAT THE ENTIRE REVIEW PROCESS AND APPLICATION PROCESS IS MUCH MORE STREAMLINED AND MUCH MORE CONDENSE THAN IN THE PAST AS WELL TO HELP WITH THAT. >> MY COMMENT IN THAT REGARD IS ACTUALLY HARDER TO WRITE 25 PAGE GRAB AND 75 PAGE GRANT. THAT'S OKAY, WE APPRECIATE THAT. SPECIFIC QUESTION ABOUT THE DOCUMENT, IS THIS PAGE 3 ESSENTIAL FEATURE TO THE NCTN INCLUDE A COORDINATED -- INCLUDE PROCESS FOR GENERATING CONCEPTS FOR RANDOMIZED FADES PHASE 2 AND 3 CLINICAL TRIALS. SHOULD I READ THAT LITERALLY THAT THERE IS NO PLACE FOR SINGLE ARM TRIALS IN THIS NETWORK ANY MORE OR IS THAT JUST NOT STATED ACCURATELY? >> I THINK THAT THE EMPHASIS IS -- FOR THIS NETWORK BECAUSE WE WERE ASKED THIS IN TERMS OF THE PORTFOLIO ANALYSIS ABOUT HOW THIS PROGRAM FITS IN WITH THE WIDER NCI PROGRAM IS OBVIOUSLY TO DO DEFINITIVE TRIALS. IT'S USUALLY RANDOMIZED PHASE 2 GOING ON TO DEFINITIVE PHASE 3 BUT YOU'RE RIGHT. NOT ALL. SO IT'S NOT TO BE READ THAT THERE WOULD NEVER BE ANY OTHER TRIALS. WHAT'S IMPORTANT IS TO HAVE A HIGH QUALITY TRIAL, THERE'S ALWAYS SOME EARLIER PHASE TRIALS WITHIN THE COOPERATIVE GROUP SYSTEM IN ORDER TO GET TO THE DEFINITIVE TRIAL, IN EXTREMELY RARE CANCER POPULATION WHERE THOSE ARE SINGLE ARM TRIALS. >> SECOND QUESTION IS EVERYBODY KNOW MISCONFLICT OF INTEREST HERE. WE HAD GONE TO A SIX YEAR CYCLE FOR THE GROUPS AND WHY THAT DEFIES -- >> I'LL LET DR. ABRAMS RESPOND TO THAT. >> THE RECOMMENDATION FOR MOST OF THE EXTERNAL REVIEW COMMITTEES SINCE WE'RE DOING THIS AT THE SAME TIME AND IT WAS GOING TO BE COMPARING PERFORMANCE WAS TO DO IT EVERY FIVE YEARS, THAT THIS WOULD BE IMPORTANT TO REDISTRIBUTE FUNDS APPROPRIATELY. AND THAT WAS A COMPLAINT OF THE PREVIOUS REVIEW SYSTEM. IT DIDN'T MATTER WHETHER YOU GOT A GOOD OR BAD SCORE. YOU GOT THE SAME MONEY. SO NOW WE WANT TO MAKE SURE THAT PEOPLE DOING A GOOD JOB GET REWARDED AND OTHERS NOT AS GOOD A JOB HAVE THEIR FUNDS REDUCED. SO IT WILL BE COMPARED ACROSS THE SYSTEM IN THAT WAY AND HAVING EVERYBODY COME IN AT THE SAME TIME IS THE WAY WE HOPE TO DO THAT. >> MY THIRD COMMENT IS ON THE REVIEW CRITERIA, AS THE MIXTURE BETWEEN SCIENCE AND OPERATIONS, AND THE WAY IT IS NOW, PROBABLY 90% SCIENCE AND 10% OPERATION WHICH IS IS NOT GOOD, I WORRY ABOUT GOING ALL THE WAY TO A 50/50 SPLIT THERE, MAYBE I'M READING IT TOO LITERALLY IN TERMS OF HOW THIS SCORE FOR YOUR GROUP WILL BE CREATED. BUT I THINK AS A STRATEGY WE WANT TO EMPHASIZE SIENTS FIRST. SO YOU CAN HAVE A GREAT OPERATIONS GROUP BUT IF THEY DON'T DO GOOD SCIENCE -- I DON'T KNOW IF THAT'S SO EXPLICITL/3M STATED OR MAYBE 75/25 SPLIT OR SOMETHING, JUST YOUR THOUGHTS IN THAT REGARD. >> I DO THINK WE THINK IT'S CRITICAL NO MATTER HOW GOOD THE SCIENCE IS, THAT IF WE CANNOT DO TRIALS IN A SUFFICIENT MANNER THAT -- AND THIS HAS BEEN A PART OF ALL THE REVIEW CRITERIA, ALL THE REVIEW GROUP, THAT ESSENTIALLY WE HAVE TO REPORT BACK WHAT WE HAVE DONE WITH THAT PUBLIC INVESTMENT. SO WE DO THINK IT CRITICAL THAT THERE BE A SIGNIFICANT COMPONENT OF THE SCORE BASED ON OPERATIONAL EFFICIENCY. SCIENCE ALSO -- ALWAYS COMES FIRST AND WE AGREE WITH THAT. BUT WE ALSO AGREE THAT IT HAS TO BE COMBINED WITH OPERATIONAL EFFICIENCY. THE OTHER IS THAT THE DISEASE-SPECIFIC STEERING COMMITTEE ALSO PROVIDE ONGOING TRIAL PRIORITIZATION OF THE SCIENCE AS WELL. AND SO THAT ASPECT GOING FORWARD IS ALSO BEING EVALUATEDDED ON THE ONGOING BASIS. >> THE OTHER IMPORTANT CRITERIA IN THE SECOND 50% IS COLLABORATION. THAT ISN'T ONLY OPERATIONAL COLLABORATION, WE'RE TALKING ABOUT SCIENTIFIC COLLABORATION THERE AS WELL SO ON SCIENCE RESEARCH OR WORKING TOGETHER ON SCIENTIFIC QUESTIONS, SO I THINK IT IS PROBABLY MORE SCIENCE THAN JUST 50/50. >> SO INCREASINGLY CORRELATIVE SCIENCE IS INTEGRATED INTO TRIALS AN ENTHUSIASM FOR THE TRIAL ITSELF AND THE CORRELATIVE SCIENCE ARE MUTUALLY DEPENDENT. IT'S A CHALLENGE WHEN THE REVIEW OF THOSE AND THE SUPPORT IS SEPARATED AND TRYING TO BRING P THEM TOGETHER IN THE SAME PLACE AT THE SAME TIME IS REALLY DIFFICULT. HOW IS THE NEW SYSTEM HELPED WITH THAT INTEGRATION? REALLY FROM THE VERY BEGINNING WHEN THE STEERING COMMITTEES FIRST HEAR OF THE CONCEPT? >> I MEAN OBVIOUSLY THAT'S PART OF THE REASON THAT WE STARTED THE BISQUICK PROGRAM IS TO MAKE SURE INTEGRATED BIOMARKERS AND QUALITY OF LIFE IMAGING THAT THOSE FUNDS WOULD BE AVAILABLE FOR DEFINITIVE AND RANDOMIZED PHASE 2 AND 3 TRIALS AND IN FACT THE APPLICATIONS FOR THAT SHOULD COME IN AT THE SAME TIME THE TRIAL IS BEING EVALUATE FORD FIRST TIME AS A CONCEPT ON STEERING COMMITTEE. THAT'S ONE WAY, OBVIOUSLY THE OTHER WAY WE HOPE TO DO THIS OR ENCOURAGE IS THROUGH THE INTEGRATE TRANSLATIONAL SCIENCE AWARD SO WE CAN ALLOW EACH OF THOSE AWARDS IN THE GROUP THAT ARE PARTICIPATING IN THEM TO BRING THE TRANSLATIONAL SCIENTISTS IN AT A VERY EARLY TIME. I THINK YOU'RE TALKING ABOUT ADDITIONAL FUNDING AS WELL AND SOMETHING WE HAVE TO THINK ABOUT AS TIME GOES ON. WE AT LEAST ARE TRYING TO INTEGRATE MORE TRANSLATIONAL SCIENCE INTO THE PROGRAM WITH FUNDING THROUGH THOSE COMPONENTS ON THIS RFA. >> SEEMS THAT 4 MILLION-DOLLAR FOR IMAGING QUALITY OF LIFE IS NOT ENOUGH. >> THE 4 MILLION-DOLLAR IN ADDITION TO WHAT WE ALREADY PROVIDE ON THE ORDER OF $10 MILLION A YEAR. SO WE ARE UPPING IT TO 14 MILLION-DOLLAR A YEAR. >> SO I WAS WONDERING ON YOUR SLIDE HOW THE NETWORK WILL HELP. AT LEAST IN TERMS OF SPECIFIC EXAMPLES LISTED THE CANCER THERAPY, CERTAINLY INCREASING FOR CASE REIMBURSEMENT THINGS WILL HELP PREVENTION AS WELL BUT WONDERING IF YOU HAVE SPECIFIC EXAMPLES OR THOUGHTS HOW THAT PROGRAM WILL HELP PREVENTION AND THROUGH CCOP OTHER THAN INCREASING PER CASE WHICH IS IMPORTANT. >> RFA IS ORIENTED TOWARDS TREATMENT BUT WE'RE WORKING WITH THE WAY WE ORGANIZED IT SO IT CAN INTEGRATE WITH CCOP AS WELL. >> WE CERTAINLY WANT TO BUILD ON ALL THE WORK THAT'S DONE AT THIS POINT N. MANY CASE IT IS COOPERATIVE GROUPS HAVE BEEN LOOKING AT CANCER PREVENTION AN CONTROL IN MORE INTEGRATED WAY. OUR EXEBLGATION IS THAT THE CCOP RESEARCH BASED RFA AS IT MOVES FORWARD WILL BE REVISED TO PARALLEL AND BE COMPLIMENTARY SO THAT WE HOPE AS THIS EVOLVES, WE CAN BEGIN TO SPEAK ABOUT CANCER PREVENTION PORTFOLIO, THERAPY PORTFOLIO AS WELL. AND CERTAINLY THERE ARE THINGS THAT WE CONSIDER UNDER CANCER CONTROL THAT CAN BE BUILT INTO SOME OF THE KAREN TREATMENT TRIALS. I KNOW DR. BRENOLE AND WE HAVE BEEN TALKING ABOUT INTEGRATING END POINTS FOR TREATMENT TRIAL, ET CETERA. SO I THINK THIS IS THE FIRST STEP. WE SEE MULTIPLE DIFFERENT PIECES OF EVOLUTION OVER TIME BUT I THINK YOU'LL SEE THE CANCER PREVENTION CONTROL WILL ALSO RISE TO THE SAME LEVELS OF EXPECTATION. ALSO IN TERMS OF CORRELATIVE SCIENCE. I WANTED TO ADD A WORD THERE, WE HAVE MADE NOTABLE PROGRESS WORKING WITH ECT MANY CANCER CONTROL STUDIES ON CTSA MENU SIMILAR TO TREAT TRIALS SO WE OPENED PARTICIPATION MORE BROADLY AND WE HAVE SEEN ACCRUAL QUITE WELL IN A NUMBER OF STUDIES SO WE HAVE SOME PRACTICAL EXAMPLES OF THIS NETWORK EFFECT STARTING TO WORK FOR US. >> SO I HAVE A COMMENT. AND JUST -- I JUST WANT TO ACKNOWLEDGE THAT IT HAS BEEN A TOUGH YEAR. IT'S BEEN VERY PAINFUL FOR US, IT'S BEEN -- US MEANING THE GROUP. IT'S BEEN VERY PAINFUL FOR Y'ALL AT THE NCI. REAL INNOVATION, REAL DISRUPTIVE INNOVATION IS REALLY HARD. I JUST REALLY THINK WE ALL WANT TO THANK YOU BECAUSE THIS WAS A COLLABORATIVE PROCESS. AND IT WAS, I THINK THIS DOCUMENT, THIS WHOLE NEW SYSTEM REPRESENTS REAL COLLABORATION BETWEEN Y'ALL, THE NCI AND THE GROUPS, SPEAKING FOR MYSELF, I THINK WE HAVE BEEN LISTENED TO, TAKEN INTO ACCOUNT OUR NEEDS, AND WE DON'T KNOW HOW THIS IS GOING TO WORK. I DON'T THINK YOU DO, I DON'T THINK WE DO. BUT WE HAVE A TEMPLATE WHERE WE FEEL WE CAN DO THIS. THAT IS REALLY IMPORTANT. THE REASON WE HAVE A TEMPLATE WHERE WE FEEL WE CAN DO THIS IS IT REALLY WAS A COLLABORATION AND OUR NEEDS WERE LISTED IN THE ADDRESS. SO THAT'S MY MAIN COMMENT AND JUST WANTED THE THANK YOU ALL. >> SO I'LL ECHO THE CONGRATULATIONS, IT IS A TRUE MILESTONE AND IT'S BEEN A LONG PROCESS THAT I KNOW MANY HAVE WORKED HARD ON. I HAVE TWO RELATED QUESTIONS FOR YOU. THE FIRST IS THIS IS A COMPLEX SYSTEM, WE KNOW THAT. ONE OF THE CHALLENGES THAT I THINK DAVID FIRST POINTED OUT AND MANY OF US RECOGNIZED THAT THE SYSTEM THAT WE CURRENTLY HAVE IS GEARED TO FAIL LATELY. THE IDEAS AND CONCEPTS AND FAIL. DO YOU THINK THIS SYSTEM WILL FUNDAMENTALLY ADDRESS THIS? IF SO, HOW WILL IT FUNDAMENTALLY ADDRESS THAT? >> CERTAINLY WE HAVE DONE SOME THINGS THAT WE ARE MOVING IN THAT DIRECTION. CERTAINLY NOT THE COMPLETE SOLUTION TO IT SO THE GUIDELINES AFFECT AFTER THE TRIAL IS UP AND RUNNING. SO THOSE GUIDELINES ARE HELPING US TO IDENTIFY AT LEAST EARLY ON WHAT CAN BE DONE TO MODIFY TRIALS THAT THEY LOOK LIKE THEY'RE NOT ACCRUING WELL. AND/OR TO IDENTIFY MAYBE IDENTIFY THEM EARLIER. SECOND OF ALL, LOOK AT THOSE SO THAT WE CAN IDENTIFY THEM IN TERMS OF THEMES SO WHEN NEW CONCEPTS COME IN FOR REVIEW WE ACTUALLY KNOW, HAVE A BETTER SENSE WHETHER THEY WOULD GO FORWARD. THE WHOLE STEERING COMMITTEE PROCESS AND MANY STEERING COMMITTEES HAVE PAST COURSES SO PEOPLE CAN WEIGH IN VERY, VERY EARLY. WE ALSO HELP -- WE ALSO HAVE MUCH MORE INTEGRATION WITH THE CTSU TO BE ABLE TO NOT ONLY MONITOR BUT MAYBE TO USE THAT CAPACITY IN A CENTRALIZED WAY TO GET FEEDBACK ON THINGS AN ON CONCEPTS VERY EARLY IN COOPERATION WITH THE GROUP. SO I THINK THERE'S A LOT MORE THAT WILL BE ABLE TO DO IN ORDER TO ADDRESS THOSE THINGS. I THINK WHAT'S VERY DIFFICULT IS WITH EACH GROUP IN A DIFFERENT REVIEW CYCLE AND ORGANIZATION, IT'S HARD SYSTEM AS A WHOLE. WE WILL NOW HAVE THE OPPORTUNITY TO DO THAT AND MONITOR IT ON ONGOING BASIS REAL TIME. I THINK THIS AS WE MENTIONED BEFORE, SHOULD START A EVOLVING PROCESS AN NEW PROCESS BUT WE'LL HAVE FAR MORE OPPORTUNITY TO SEE THE THINGS WE SHOULD DO IN ORDER TO DO EXACTLY WHAT YOU SAID BECAUSE WE WOULD ALL RATHER DO THAT. WE'RE GOING TO FAIL, WE'D RATHER FAIL EARLY THAN LATE. >> SO THE RELATED QUESTION, I HAVEN'T HAD A CHANCE TO G THROUGH THE DOCUMENT YOU SEN AROUND IN DETAIL, BUT HOW TO DO SCIENCE WE'RE HEADING INTO EFFICIENTLY AND EFFECTIVELY IS SOMEWHAT OF AN UNKNOWN. ARE THERE WORDS HERE AND LANGUAGE THAT INCENTIVIZE INNOVATION HOW WE DO OUR SCIENCE? AS OPPOSED TO SAY THIS IS HOW WE SHOULD DO THE SCIENCE? >> THERE ARE WORDS IN THERE. CERTAINLY INNOVATIVE -- >> NOT THAT INNOVATION IN SCIENCE BUT INNOVATIONS HOW WE DO IT. HOW ARE WE DOING THINGS EFFICIENTLY? >> I THINK THERE ARE TWO THINGS THE INTEGRATED TRANSLATIONAL AWARDS WHICH WILL BE A COMPETITIVE REVIEW FOR TRANSLATIONAL SCIENCE UNDER SCIENTIFIC THINGS IS ONE WAY P THAT PEOPLE COME IN WITH INNOVATIVE IDEAS PEER REVIEWED. SO I THINK THAT WILL HELP THAT'S ONE THING. THE OTHER THING WE SHOULD EMPHASIZE, THIS REFLECTS A LITTLE BUILT AS WELL WHAT MONICA SAID, GOING FORWARD THERE WILL BE COLLABORATIVE MANAGEMENT OF THE ENTIRE NETWORK OF ALL THIS TOGETHER. THAT WILL HELP IN TERMS OF IDENTIFYING HOW IN AN INTEGRATED NETWORK WE DO SOME OF THE THINGS YOU'RE SAYING. I THINK IT IS DIFFICULT WHEN YOU HAVE TEN SEPARATE GROUP, ALL OPERATING SEPARATELY TO ADDRESS THE INNOVATIONS THAT PROBABLY WOULD BE EXTREMELY BENEFICIAL, PARTICULARLY IN RARE SUB SETS NEW OPPORTUNITIES IN TERMS OF CANCER RELATED PATHWAYS FOR AGENTS ACROSS DISEASE TIMES. >> -- TYPES. >> THAT'S VERY IMPORTANT BUT I WANT TO PERHAPS ANOTHER ASPECT OF PETER'S QUESTION IS WE'RE NOT CREATIVE AND INNOVATIVE IN THE SENSE THAT WE'RE PUTTING DOWN GUIDELINES OR THE TRANSLATIONAL SCIENCE AWARD, BUT WE'RE NOT TELLING GROUPS HAD TO DO THAT. I'M SURE PEOPLE WILL BE CREATIVE AND DO IT IN DIFFERENT WAYS. HOPEFULLY SHARE THE GOOD THINGS SO WE CAN LEARN FROM EACH OTHER WHAT WORKS AND WHAT DOESN'T. I DON'T THINK THERE'S ANY LACK OF CIVILITY FOR EACH ORGANIZATION TO DO THINGS THAT MAKE SENSE FOR THEM AND SOMEWHAT DIFFERENT WAYS AS LONG AS THEY RESPECT THE OVERALL GOAL, BOTH EFFICIENCY AND COLLABORATION. (OFF MIC) >> SO ANOTHER MN DANE QUESTION, WHAT'S THE REVIEW PROCESS GOING TO LOOK LIKE? AFTER ALL THOSE APPLICATIONS COME INTO BETHESDA A YEAR FROM NOW? >> BECAUSE YOU HAVE EVALUATION CRITERIA BUT WHO IS GOING TO APPLY -- WE HAD PRELIMINARY DISCUSSIONS OF EXTRAMURAL ACTIVITIES. BUT IT'S A BIG WORLD, EVEN WITHIN THE UNITED STATES. SO WE DO FEEL THAT WE WILL BE ABLE TO HAVE REVIEW PANELS THAT WILL BE ABLE TO ADEQUATELY REVIEW THE COMPONENTS. YOU WILL HAVE TO HAVE MUCH MORE ATTENTION TO CONFLICT OF INTEREST BECAUSE ALL THE GROUPS WILL BE COMING IN TOGETHER. WE DO HAVE THE OPPORTUNITY TO GET REVIEWERS FROM OTHER COUNTRIES AS WELL. BUT WE DO BELIEVE IN THE UNITED STATES THAT ACTUALLY WILL BE ABLE TO GET A REVIEW CRITERIA OR REVIEWERS TOGETHER WITH EACH OF THE PANELS WITHOUT CONFLICTS AND WE HAVE HAD PRELIMINARY DISCUSSIONS HOW TO DO THAT, HOW TO ROLE IT OUT, TYPES OF REVIEWERS THAT WE HAVE. >> I ALSO WANTED TO JUST COMMENT, A LOT OF PEOPLE PUT WORK IN AND CONGRATULATE PEOPLE FOR THIS. I WANT TO FOLLOW-UP ON A COMMENT RELATED TO THE WORK WE DO IN AKRON AND HOW IT'S ACCOMMODATED IN THE NEW NETWORK. YOU FOCUSED ON THE IDEA OF THERAPY, THERAPY, THERAPY. PART OF WHAT WE DO IS LOOK AT IMAGENING THE CONTEXT OF MARKERS FOR THERAPY STUDIES, FUNDED THROUGH DCTD THROUGH OUR CIT GRANT TO DO STUDIES LOOKING AT THE IMPACT OFK-PgG AND IMAGING DIAGNOSTIC, ON PATIENT OUTCOMES FOR EXAMPLE. THOUGH NOT NECESSARILY SCALED RIGHT NOW FOR THIS BUT THAT'S AN EXAMPLE OF AN OUTCOME RELATED TO IMAGING INTERVENTION. THAT DOESN'T COUNT UNDER THOSE 20,000 ACCRUALS YOU'RE SUGGESTING WITHIN DCTD, DCTD STILL INTERESTED IN THESE STUDIES? SO IT'S NOT PURELY THERAPY-DRIVEN NETWORK. >> YOU'RE RIGHT. YOU MAKE A VERY GOOD POINT. WITHIN THIS GROUP WE'RE ADDING IMAGING AKRON IMAGING NETWORK INTO IT. IT'S NOT COMPLETELY HARD TO MAKE EXACT DEFINITIONS OF THIS BUT IT WOULD NOT BE LIMITED JUST TO THE TREATMENT ASPECT, IT ALSO INVOLVES IMAGING TRIALS AS WELL AND THE ENTIRE ACCRUAL WAS BASED ON ALL OF THAT. >> LIKEWISE, GREAT JOB. I WANT TO ASK YOU SOMETHING ABOUT SOMETHING YOU DIDN'T TALK ABOUT WHICH IS THE TUMOR BANKING. VERY INTERSD HOW THIS WOULD BE -- INTERESTED WHAT ARE THOUGHTS HOW THIS WOULD BE INCORPORATED? >> WELL, THE TUMOR BANKS AS YOU KNOW THERE HAVE BEEN QUITE A FEW DISCUSSIONS ABOUT THAT. RIGHT NOW THE CANCER DIAGNOSIS PROGRAM AND BARB IS HERE IS GOING THROUGH A LITTLE BIT OF THE SAME PROCESS THAT WE WENT THROUGH IN TERMS OF THINKING ABOUT HOW TO COME THROUGH WITH A NEW RFA, THEY'LL BE MEETING WITH STAKEHOLDERS INCLUDING THE COOPERATIVE GROUP CHAIRS AND THE GROUP BANKING COMMITTEE TO TRY TO DEFINE HOW BEST TO GO FORWARD WITH TUMOR BANKING SUPPORT GIVEN THIS NEW NETWORK. WE WAITED, OBVIOUSLY AS YOU KNOW, THE BSA MEETING IN JUNE. THERE WAS A VOTE BY THE BSA TO DEFER GOING FORWARD WITH THE NEW RFA FOR THE TUMOR BANKS UNTIL THE COOPERATIVE GROUPS OR INTEGRATED CLINICAL TRIALS NETWORK RFA WAS BETTER DEFINED. THAT'S AS MUCH AS I CAN PERSONALLY TELL YOU RIGHT NOW. >> I HAVE A PROCESS QUESTION AND THEN A COMMENT. ONE OF THE SLIDE OVERVIEW OF THE RFA, THERE'S 30 OR 40 LEAD ACADEMIC+ PARTICIPATING SITES. WILL THEY BE REVIEWED AT THE SAME TIME? >> YES. THIS IS MORE THE PATIENTS THINK THE SYSTEM IS ORGANIZED, THE CONCEPT OF A COMMON DATA STANDARD AND COMMON DATABASECH WHEN I TELL PEOPLE THAT'S NOT HOW IT IS NOW, SO IT'S GREAT SEE THIS MOVING FORWARD, I WISH IT WOULD MOVE FASTER BUT I REALIZE THAT'S PRACTICALLY NOT POSSIBLE BUT THERE'S A BIG SENSE OF URGENCY ON OUR SIDE TO KEEP IT GOING. SO THANK YOU. I WISH YOU LUCK WRITING YOUR GRANTS. >> WE HAVE A FEW MORE MINUTES IF PEOPLE HAVE A FEW EXTRA QUESTIONS. IF NOT, THANK YOU VERY MUCH, VERY NICE PRESENTATION. [APPLAUSE] SO WE WILL MOVE ON TO THE NEXT PRESENTATION WHICH IS GOING TO BE JOEL TEPPER. AS YOU REMEMBER, I GUESS WE HAVE SOME NEW MEMBERS, OUR LAST MEETING WE DID AUTHORIZE THE FORMATION OF A CTAC STRATEGIC PLANNING AD HOC SUB COMMITTEE WHICH IS REALLY CHARGED WITH OVERSEEING THIS PROCESS OF CREATING CLINICAL TRIALS NETWORK. IN PARTICULAR AS JOEL OUTLINED, THERE ARE SPECIFIC AREAS THAT ARE WE FEEL ARE THE MOST IMPORTANT TO BEGIN TO EXAMINE THE SUBCOMMITTEE MET LAST EVENING, YOU'LL SEE A COMPOSITION OF THIS AND SOME OF THE DISCUSSION THAT TOOK PLACE IN OUR PLANS GOING FORWARD. >> SO I WILL KEEP MY COMMENTS BRIEF. AS JIM MENTIONED THE MEMBERS OF THIS CLINICAL TRIALS STRATEGIC PLANNING SUBCOMMITTEE ARE LISTED HERE. TAS SMALL GROUP, AS YOU SEE THERE'S A LOT OF PEOPLE THAT WILL LIKELY BE INVOLVED AS WE MOVE ON. THE RATIONAL FOR THIS IS THERE'S A LOT OF CHANGES MADE AND A LOT OF CHANGES THAT WILL BE MADE IN THE SYSTEM EVER SINCE THE CTWG REPORT CAME OUT. AND IT WAS DECIDED THAT WE NEEDED TO EVALUATE WHETHER WE WHAT WE'RE DOING IS WORKING AT ALL IN TERMS OF SCIENTIFICALLY WORKING EFFICIENCY WORKING AND GETTING ACTUALLY SOME GOOD END RESULTS. SO WE NEEDED A PLAN TO ASSESS THE PERFORMANCE AND IMPACT OF THE CTWG INITIATIVES AND OTHER INITIATIVES AS THEY COME ALONG ON EFFECTIVENESS OF THE WHOLE CLINICAL TRIAL ENTERPRISE AS WE MOVE FORWARD. THE AREA OF GREATEST INTEREST IS REALLY IN THIS WHAT'S NOW THIS NCTN. IT'S WITH A FEELING THAT REALLY EVERYONE NEEDS FEEDBACK IN TERMS OF HOW THE SYSTEM IS WORKING, CERTAINLY A LOT OF IT IS THAT NCI NEEDS FEEDBACK THROUGH CTAC AND THROUGH EVALUATION OF CTAC IN TERMS OF WHAT IS WORKING IN THE SYSTEM, WHAT ISN'T WORKING IN THE SYSTEM. SO THERE CAN BE CHANGES MADE IN THE SYSTEM TO MAKE IT BETTER. IT'S CLEARLY THERE ARE SO MANY PHASES THAT THEY'RE CLEARLY GOING TO BE MISTAKES, THERE WILL BE THINGS THAT AREN'T WORKING RIGHT, OTHERS THAT ARE, WE NEED TO TRY TO UNDERSTAND WHAT THEY ARE. RIGHT NOW WITH THE FORMATION WITH THE STEERING COMMITTEE, STEERING COMMITTEES AND LIKE, THERE IS A SENSE OF WHAT'S GOING ON I PRESENTED TO THIS GROUP ABOUT THE OPERATION WITHIN THE STEERING COMMITTEE, BUT IT REALLY NEEDS TO BE MUCH BROADER, NEEDS INVOLVEMENT CCOP AND THE LIKE. PART OF THIS IS TO BE ABLE TO ASSESS PRIORITIES ACROSS THE MODALITIES. ONE THING THAT HAPPENS RIGHT NOW, THERE IS SOME LEVEL OF PRIORITIZATION WITHIN THE INDIVIDUAL STEERING COMMITTEE AS BEST I KNOW THERE IS NO PRIORITIZATION ACROSS THE STEERING COMMITTEE. SO ONE GROUP MIGHT APPROVE HUGE NUMBERS OF TRIALS AND OTHERS WHO DONE AND THAT'S WHAT YOU GET. THAT MIGHT NOT BE AND PROBABLY ISN'T THE BEST USE OF NCI RESOURCE WHICH IS WE HEARD CONTINUES TO GO DOWN. WE WANT THE FEEDBACK TO BE -- THOUGHT LEADERS REMINDING, BOTH WITHIN AND OUTSIDE THE GROUP. AND CLEARLY THIS EVALUATION SHOULD BE COMING THROUGHw. CTAC. THIS IS A MAJOR ROLE THAT THE CTAC HAS A AND A MAJOR REASON CTAC WAS FORMED TO DO THIS. ONE EMPHASIZES THIS WAS NOT A PROTOCOL SPECIFIC REVIEW. THIS IS REALLY A SYSTEM REVIEW LOOKING AT PORTFOLIO EVALUATION AND NOT INDIVIDUAL STUDIES WHETHER THOSE ARE GOOD OR THOSE STUDIES ARE NOT SO GOOD. SO THE PURPOSE OF THE CLINICAL TRIAL STRATEGIC PLANNING SUBCOMMITTEE IS TO ADVISE NCI ON THE DEVELOPMENT OF THIS FULLY INTEGRATED CLINICAL TRIAL SYSTEM AND THE MODIFICATIONS OF THAT SYSTEM AS TIME GOES ON. THE SCOPE OF THIS, TRIALS FUNNED PREDOMINANTLY THROUGH COOPERATIVE AGREEMENTS AN CONTRACT, THE CLINICAL TRIALS NETWORK THAT WE JUST HEARD ABOUT, ALMOST ALL THESE, STEERING COMMITTEES AND CONDUCTED BY THE COOPERATIVE GROUPS CCOP, NOT 100 PERCENT NECESSARY THIS HAPPEN BUT IN ESSENCE IT IS WHAT HAPPENS. THERE ARE ALSO THE EARLY PHASE TRIALS, IT'S IMPORTANT THAT INITIALLY TO FOCUS ON THE CLINICAL TRIALS NETWORK FOR THE EVALUATION WE TALKED ABOUT THIS A FAIR BIT AND WE TRIED TO LIMIT OUR SCOPE AS WE START OFF SO THAT WE CAN ACTUALLY GET SOMETHING DONE. , THEY'RE NOT TRYING TO BE GLOBAL. TO LOOK AT THE ENTIRE CLINICAL TRIAL SYSTEM AND BRING MANY, MANY OTHER AREAS THAT WOULD BE FAR TOO EXTENSIVE TO LOOK AT AT LEAST INITIALLY, THAT'S NOT TO SAY THAT THAT WOULD NOT BE DONE AS TIME MOVES FORWARD. SO THE SPECIFIC OBJECTIVES OF THE SUBCOMMITTEE TO MONITOR AND ASSESS THE BALANCE COHERENCE APPROPRIATENESS OF THE NCI CLINICAL TRIALS PORTFOLIO, KEEP IN MIND ISSUES SUCH AS BALANCE, COHERENCE AND APPROPRIATENESS ARE NOT EXACTLY SCIENTIFICALLY RIGOROUS TERMS THAT HAVE ANSWERS THAT ARE EASILY DEFINED, IT IS A HUGE ISSUE IN TERMS OF HOW WE APPROACH THESE AND HOW THESE ARE DEFINED. THE MONITOR AN ASSESS THE SCIENTIFIC EFFECTIVENESS OF THE THE SCIENTIFIC STEERING COMMITTEE, PART IS DONE BY PRETTY CAREFUL METRICS IN TERMS OF EFFICIENCY AND IN TERMS OF HOW LONG IT TAKES CERTAIN THINGS TO HAPPEN. BUT SCIENTIFIC EFFECTIVENESS IS NOT AS EASY, AGAIN, THERE IS LIKELY TO BE SOME SIGNIFICANT LEVEL OF SUBJECTIVITY ON THIS AND THIS WILL NEED TO BE DISCUSSED AT SUBSTANTIAL LENGTH. AND THEN TO RECOMMEND NEW%q STRATEGIES PRIORITIES AN DIRECTIONS FOR CLINICAL TRIALS, BASED ON THE CURRENT PORTFOLIO. EVOLVING CLINICAL NEEDS AND EMERGING OPPORTUNITIES AND MONITOR AND ASSESS OTHER ASPECTS OF THE OPERATIONS ACROSS THE DISTANCE, INCLUDING COLLABORATION AND TIMELINESS. I THINK WE ALL AGREE THESE ARE IMPORTANT ISSUES BUT ADMITTEDLY SO, THESE ARE NOT AS EASILY DEFINED IN TERMS OF CLEAR CUT METRICS BUT THERE ARE SOME WAYS THIS IS APPROACHED. I SHOULD HAVE MENTIONED EARLIER A LOT IS GOING TO BE BUILT ON EVALUATION SUBCOMMITTEE WITH DAN TAR GENT AND PETER ADAMSON WHICH IS REALLY THE BASIS FOR MOST OF THE EVALUATION GOING FORE. THAT GROUP SPEB A LOT OF TIME -- SPENT A LOT OF TIME PUTTING TOGETHER THE REPORT AND METRIC THAT WILL BE THE BASIS FOR MUCH OF THIS EVALUATION. AND WITHIN THAT GROUP THERE WAS STRUGGLING WITH SUBJECTIVITY ISSUES AND SO SOME OF THESE OUTCOMES WILL BE MEASURED IN TERMS OF ISSUES -- PUBLICATIONS, PUBLICATIONS AND HIGH QUALITY JOURNALS, SOME ARE ASSESSED BY PANELS, BY SURVEY INSTRUMENTS AND THE LIKE, PEOPLE'S OPINIONS AS TO HOW THINGS ARE WORKING. DAN PAY WANT THE COMMENT MORE WHEN WE GET INTO DISCUSSION. THE STRUCTURE OF HOW WE DO THIS, WE HAVE CTAC UP TOP. THE SUBCOMMITTEE THAT I JUST DISCUSSED BELOW THAT WE REPORT THROUGH THIS GROUP REPORT TO CTAC. A LOT OF WORK IS DONE AT THE LEVEL OF CLINICAL TRIALS STRATEGIC PLANNING WORKING GROUP. THIS WORKING GROUP NEEDS TO ADDRESS MANY ISSUE, COME UP WITH RECOMMENDATIONS FOR WHICH THE SUBCOMMITTEE WOULD BE INVOLVED IN THAT PROCESS PULL THESE TOGETHER IN AN APPROPRIATE WAY AND THEN REPORT TO CTAC. THERE WAS TAWNG EARLY ON ABOUT HAVING OTHER WORKING GROUPS BUT WE HAD DISCUSSED THIS AND DECIDED IT WOULD BE A GOOD IDEA TO INITIALLY STICK JUST WITH THE CLINICAL TRIALS WORKING GROUP AS THE MAJOR FOCUS. THAT WILL LIKELY COME UP IN THE FUTURE. WHAT IS THE COMPOSITION OF THIS WORKING GROUP. WE DISCUSSED THIS A FAIR BIT LAST NIGHT AND IT CAME UP WITH A POSSIBLE MEMBERSHIP CATEGORY THAT ARE LISTED HERE, IN AN ATTEMPT TO GET FAIRLY WIDE INPUT. THAT'S A PROBLEM HERE OBVIOUSLY OF HAVING TOO MANY PEOPLE SO YOU CAN GET ANYTHING DONE OR NOT ENOUGH TO GET ANYTHING DONE. WE PROBABLY END UP WITH A WORKING GROUP ON THE ORDER OF 25 OR 30 PEOPLE LIKELY REMEDY VIEDING THIS UP INTO SMALLER GROUPS WHO COULD HAVE -- THAT WOULD BE ABLE TO ADDRESS SPECIFIC ISSUES IN THE EVALUATION PROCESS AND THEN LARGER GROUP GETTING TO TO GET FEEDBACK TO THE SMALLER GROUPS. IT'S AN APPROACH USED PRETTY MUCH LIKE THAT IN THE OPERATIONAL EFFICIENCY WORKING GROUP, THE PART WORKED OUT FAIRLY WELL, A LOT OF WORK DONE SEPARATELY AND THEN TOGETHER. WE ACTUALLY TALKED ABOUT THE NUMBERS THAT MIGHT BE PUT HERE AND THERE WOULD BE A FAIR AM OF LIKELY OVERLAP THE NUMBER OF PEOPLE WOULD BE WEARING TWO HATS OR EVEN THREE HATS TO BE ABLE TO REPRESENT DIFFERENT GROUPS, BUT WE WOULDN'T BE HAVING CANCER CENTER DIRECTORS OR ANYTHING LIKE THAT. THEY WOULD BE REPRESENTING EACH OF THESE AREAS. SO CRITICAL IN THIS PROCESS. WE CAN TALK ABOUT THAT AND GET A LITTLE BIT MORE IN DISCUSSION TIME. THE NEXT STEP WOULD BE TO DRAFT A FUNCTION STATEMENT AND PROPOSED MEMBERSHIP OR AGREE ON THE MEMBERSHIP FOR THIS WORKING GROUP AND WE WOULD LIKE TO GET FEEDBACK ON THAT DURING THIS MEETING. AND THEN NCI WOULD CONTINUE TO IMPLEMENT THE EVALUATION PLAN. THERE'S DATA THAT NEEDS TO BE PUT TOGETHER. SOME OF THE EVALUATION METRICS RECOMMENDED BY THE EVALUATION SUBCOMMITTEE THAT DAN AND PETER SHARED, ARE DATA THAT CAN BE PULLED OUT FAIRLY EASILY, THEY ARE NUMERIC, THEY CAN'T BE DEFINED, OTHERS REQUIRE MORE EFFORT NORTH TO GET THAT INFORMATION. SO NCI WOULD PRESUMABLY BE PROCEEDING WITH THIS(PL AS WE'RE FORMING THE WORKING GROUP AND THE WORKING GROUP WAS STARTING ITS WORK. AND THE INITIAL WORK GROUP ACTIVITIES WOULD BE TO FIRST OF ALL UNDERSTAND WHAT THAT -- WHAT THEY WERE SUPPOSED TO DO, TO LOOK OVER THE PROPOSED MEASURES AND THE METRICS TO SEE WHETHER THIS WOULD LIKELY HELP THEM ACHIEVE THE TASK. AND DEVELOP A PROCESS FOR ANALYZING THE PORTFOLIO, ASSESSING THE BALANCE BASED ON INPUT FROM A VARIETY OF GROUPS. SO WITH THAT I WILL STOP AND I THINK WE CAN OPEN IT UP TO DISCUSSION. -- IN TERMS OF EVALUATION >> I DON'T KNOW IF I HAVE TOO MUCH TO ADD. I THINK STARTING THE FOCUS TO MAKE SENSE, I THINK THERE WILL BE PRESSURE TO EXPAND WHAT YOU COVER. BUT I CERTAINLY CONCUR WITH WHERE YOU'RE BEGINNING BECAUSE YOU'RE RIGHT. THERE ARE A NUMBER OF MEASURES THAT ARE GOING TO BE LOW HANGING FRUIT AND PERHAPS A LARGER NUMBER THAT ARE MORE SUBJECTIVE THAT WILL NOT BE SO EASY TO TACKLE. I THINK TRYING TO STAKING THIS STEP WISE IS THE RIGHT WAY TO GO. ARE THERE ANY ADDITIONAL QUESTIONS? SO THIS GEOFF, IT'S JUST A LITTLE UNCLEAR TO ME THIS IS AN OVERSITE ROLE IN THE SCIENTIFIC STEERING COMMITTEES AND IF SO, HOW IS THIS COMMITTEE GOING TO THEN COMPEL CHANGE IN TERMS OF SCIENTIFIC COMMITTEE. SPECIFICALLY WOULD IT LOOK AT HOW THE STEERING COMMITTEES ARE REVIEWING PROTOCOLS, HOW RIGOROUS THEY ARE? BECAUSE IT'S DIFFERENCE BETWEEN SCIENTIFIC COMMITTEES AND THERE MAYBE SOME ROLE TO TRY TO GET MORE BALANCE AMONG THAT. IS THIS COMMITTEE OVERLOOK THAT? >> THE STEERING COMMITTEES ARE CREATIONS OF NCI. AND THEREFORE NCI CAN SIT UP THE GROUND -- SET UP GROUND RULES FOR HOW THOSE STEERING COMMITTEES WORK. CTAC'S JOB IS TO ADVISE NCI AS TO ISSUES RELATED TO THE CLINICAL SYSTEM INFORMATION FROM THE WORKING GROUP TO THE EVALUATION SUBCOMMITTEE IF THERE ARE CHANGES THAT NEED TO BE MADE I SUSPECT THERE WILL BE SOME SIGNIFICANT CHANGES THAT WOULD NEED TO BE MADE, THEY WOULD BE IMPLEMENTED BASED ON ADVICE GOING THROUGH THE SYSTEM. CLEARLY CERTAIN ASPECTS ARE RELATED TO INDIVIDUAL PERSONALITIES AND THE LIKE YOU CAN FEEL UP POTENTIALLY SET UP PARAMETERS TO CLEAN THOSE OFF IN TERMS OF WHETHER THINGS ARE ADEQUATELY PRIORITIZED. SO I THINK IT CAN BE -- THINGS CAN BE EASILY FOUND OUT, SOME WHICH CAN BE CHANGED, SOME WHICH ARE HARDER TO CHANGE. TO HAVE A LEADER STHAIP'S NOT WORKING WITH THE STEERING COMMITTEE AND IS NOT FUNCTIONAL, WELL, IMAGINE THAT COULD BE CHANGED. >> SEE HOW WELL THEY'RE FUNCTIONING FOR EXAMPLE WHEN CLINICAL TRIALS PLANNING MEANING (INAUDIBLE) WAS MOVING SCIENTIFIC AGENDA WITHIN THE STEERING COMMITTEE FORWARD. AND THEN LOOKING AT THE OVERALL BALANCE OF THINGS COMING OUT, SPECIFIC STEER COMMISSION SO SOME MORE DETAILED MEASURES THAT WERE PROPOSED AND THEN LOOKING AT THE BALANCE IS A BIG PART OF IT. >> SO I UNDERSTAND WHY YOU WOULD START WITH A GROUP OF A NETWORK PORTFOLIO GIVEN THAT IT PROBABLY IS BEEN THE MOST ORGANIZED AND EASIEST TO GET YOUR ARMS AROUND BUT I THINK FOR THE SAME REASON IT'S EASIEST, IT IS PROBABLY THE MOST SCRUTINIZED. AND TALKED ABOUT PART OF THE PORTFOLIO. AND SO I WOULD JUST ENCOURAGE LOOKING BEYOND THE GROUP PORTFOLIO RELATIVELY QUICKLY BECAUSE I THINK THAT THERE IS A NEED FOR SIMILAR SCRUTINY AND ORGANIZATION AROUND THE ENTIRE PORTFOLIO BUT NOT THE MAJORITY. >> WE TALKED ABOUT THIS LAST NIGHT, A LOT OF NCI DOLLARS THAT GO TO OVER PARTS OF THE CLINICAL TRIAL PORTFOLIOS. SOME ARE FAR MORE DISPERSED AND POORLY ORGANIZED, THE PORTION UNDER RO-1 IS GOING TO BE VERY HARD TO GET HANDLE ON THAT. THE REASON IT'S HARDER TO BE ABLE TO MANAGE IT, THIS IS A BETTER CHANCE OF BEING ABLE TO MANAGE THAT. >> THAT'S NOT A REASON TO AVOID IT. >> WE'RE NOT AVOIDING IT BUT I THINK WE NEED TO LEARN FROM WHAT WE DO WITH THIS. SO WE CAN MOVE ON. BUT THIS IS GOING TO BE A BIG EFFORT. AND JIM AND I TALKED LAST NIGHT WE NEED TO MOVE FORWARD. I TOTALLY AGREE WITH WHAT YOU'RE SAYING BUT IT'S HARD. >> ONE OF THE MOST INTERESTING PRESENTATIONS I HAVE THE OPPORTUNITY HERE SINCE I HAVE BEEN ON THE COMMITTEE WAS THE PRESENTATION OF THE OVERALL NCI CLINICAL TRIALS PORTFOLIO WHERE MONEY GO. THIS WAS A VERY HIGH-LEVEL DISCUSSION. BECAUSE I THINK LACK OF DATA OR MAYBE THE TIME TO GATHER THE DATA, IT'S HARD TO DRILL DOWN FURTHER. BUT WE HAVE A NUMBER OF NEW MEMBERS OF THE COMMITTEE AND I HAVE BEEN THINKING ABOUT THIS THE LAST FEW WEEKS WHETHER PEOPLE WOULD WANT TO HEAR THAT PRESENTATION AGAIN. I THOUGHT IT WAS EYE OPENING HOW MUCH MONEY TOTAL IS COMMITTED BY THE NCI TO CLINICAL TRIALS AND WHERE IT'S BEING DONE. AND I THINK AS I RECALL, IT'S ABOUT A HALF HOUR OR SO PRESENTATION. IT'S EYE OPENING. I THINK IT'S -- SO WHAT DO PEOPLE THINK? WE HAVEN'T DONE THAT BEFORE ON THE COMMITTEE TO HAVE REPRIZE PRESENTATION. >> WE CAN CUT A CD. >> BUT PEOPLE WOULD BE INTERESTED IN -- BECAUSE WE HAVE A NUMBER OF >> SO YOU KNOW WHAT IT IS, THE SCIENCE TECHNOLOGY INSTITUTE ANALYZE THE COST ACE CROSS THE INSTITUTE TOWARDS -- FOR CLINICAL TRIALS. SO INCLUDING THE INTRAMURAL PROGRAM, AND THE GRANT PORTFOLIO, IT WAS BASED ON 2006 DATA. BUT IT WAS DONE TO DEVELOP -- TO DEVELOP FEASIBILITY TO DO THAT. THAT'S WHAT THE PRESENTATION THE MODALITIES, TO SHOW IT WAS FEASIBLE AND THEN SO YOU CAN SEE WHAT THE PORTFOLIO LOOKS LIKE IN 2006, IT HAS NOT BEEN DONE SINCE THEN. AND ONE OF THE QUESTIONS SHOULD WE EVER DO THAT AGAIN. BUT THAT IS --S THAT WHAT WAS PRESENTED HERE PROBABLY TWO YEARS AGO NOW. >> WE THINK THAT'S PART OF THE WHO PROCESS AND THEN SHE DOESN'T DO IT AGAIN. OF COURSE. SUSPECT THAT PART AND PARCEL OF WHAT WE'RE TRYING TO DO WITH CREATING A NATIONAL CLINICAL TRIALS NETWORK IN THAT WE ARE BEING ASKED TO SERVE AS A RESOURCE FOR OTHER NCI FUNDED GROUPS, AND -- NO-1s RO-1s, ET CETERA, WITHOUT KNOWING HOW THAT IS DISTRIBUTED. MAYBE WE DON'T NEED TO KNOW BUT WITHOUT THE STRATEGIC PLANNING COMMITTEE KNOWING HOW THOSE DECISIONS ARE BEING MADE IN 2011, HOW CAN WE EFFECTIVELY MANAGE WHAT WE NEED TO DOEN OUR DOWN STREAM? >> I THINK IT WOULD BE HELPFUL TO >> LET ME ASK ANOTHER THING. IN ADDITION TO THE DOLLARS, THIS IS CREDIT TO SHEILA, WE WORKED HARD TO ACTUALLY DEVELOP A DATABASE. YOU HAVE HEARD PRESENTATIONS ABOUT THIS, WE KEEP -- WE'RE MAKING INCREMENTAL PROGRESS. I THINK IT WILL BE ANEST MABL VALUE TO THIS COMMITTEE AND THE ENTIRE CLINICAL RESEARCH COMMITTEE TO KNOW WHERE EVERY CLINICAL TRIAL THAT IS SUPPORTED BY NCI DOLLARS IS AND WHAT (INAUDIBLE). THAT GOES HAND IN HAND WITH KNOWING WHERE THE DOLLARS ARE. >> SO FIRST IT'S THE PEOPLE WHO HAVEN'T SEEN IT, IT'S HARD TO SAY WHETHER THEY WANT TO SIT OR NOT BUT THERE WAS WORTHWHILE SEEING. BUT IT COMES UP -- IT'S PROBABLY WORTH SEEING AGAIN. I THOUGHT -- MY REACTION WAS THAT WE DID MAKE A RECOMMENDATION THAT IT WAS EASY FOR US TO MAKE A RECOMMENDATION TO DO IT AGAIN, IT WAS A LOT OF WORK BUT FOR ME IT'S LIKE TO SEE IT AGAIN JUST TO HAVE SOME VALIDATION THAT THOSE NUMBERS WERE OKAY AND SEE IF THERE IS ANY CHANGES IN TIME AND EVERYTHING -- RELEVANT TO WORTH BRINGING IT BACK. >> I ABSOLUTELY AGREE. SINCE MANY HAVEN'T SEEN IT WE SHOULD SEE IT AGAIN. AS FAR AS DOING THE ANALYSIS AGAIN, I WOULD ARGUE UNTIL WE HAVE A PLAN FOR WHAT WE'RE GOING TO DO, WE KNOW THERE IS A LARGE PORTFOLIO OF MONEY NOT FALLING IN THIS ANALYSIS SO UNTIL WE WE HAVE A PLAN FOR WHAT WE'RE GOING TO DO, WE'RE SORT OF WASTING TIME SAYING WE'LL DO THE ANALYSIS AGAIN. IF IT HAS CHANGED I CAN'T IMAGINE IT'S CHANGED LOGARITHMICALLY OR DRAMATICALLY. SO THE DATA WILL SPEAK FOR THEMSELVES. I THINK OUR CHARGE WILL BE HOW DO WE ADDRESS IT. >> I HAVE A DIFFERENT VIEW. SO MUCH HAS CHANGED IN GENOMIC MEDICINE, TRANSLATIONAL, MOVING SCIENCE INTO DRUG DEVELOPMENT. I CAN SEE SUBSTANTIAL FUNDS GOING TO DIFFERENCE AREAS, IT'S HARD FOR US TO INFORM A CERTAIN AREA WHICH MAYBE A LOW HANGING FRUIT BUT NOT VERY FUNDED WITHOUT KNOWING THE CONTEXT OF WHERE FUNDS ARE GOING. IT HELPS US INFORM YOU KNOW. WE'RE GOING AFTER SPECIFIC PROGRAMS. I THINK IT'S USEFUL TO RENEW IT. >> THE POINT IF WE'RE GOING TO RENEW IT WE NEED TO PUT A WORKING GROUP AROUND THAT ABLE TO MAYBE NOT TALK ABOUT SPECIFIC POLICY DISCUSSIONS BUT IN TERMS OF STRATEGIC OPERATIONAL ORGANIZATIONAL ISSUES START PUTTING A WRAPPER AROUND IT. >> I DON'T CARE WHAT HAPPENED IN 2006. I CARE ABOUT WHAT HAPPENED IN 2011, AS MONICA SAID. HOW FEASIBLE IS IT TO REDO THIS? IS THIS AN EXERCISE IT TOOK A WEEK, A MONTH, A YEAR? I'M SURE IT TOOK MORE THAN A WEEK. THREE YEARS. BUT MAYBE WE HAVE A DATABASE NOW THAT CAN HELP US WITH THAT. I MEAN -- >> RIGHT. SO JUDY (INAUDIBLE) BUT I WILL TELL YOU ONE IT COSTS MONEY, TWO, IT DID TAKE A SUBSTANTIAL AMOUNT OF TIME, IT WAS 2006 ANALYSIS, REALLY WAS TO DEVELOP THE FEASIBILITY. SO IN THEORY IT SHOULD BE EASIER TO DO IT IN THE FUTURE BUT THERE ARE THINGS THAT NEED FINE TUNING FROM LOOKING AT METHODOLOGY AND THINGS THAT WERE USED. IT WOULDl NEED TO BE DONE. >> CHRONOLOGICALLY THE ANALYSIS TOOK A FAIR AM OF TIME. PARTIALLY BECAUSE IT GOT PUT ON THE BACK BURNER AND PARTIALLY BECAUSE SOMETIMES GETTING THE INFORMATION FROM PEOPLE EVEN IF THEY HAD IT DIDN'T COME AS PROMPTLY. BUT WE DID WORK OUT A METHODOLOGY WHICH AT THE RISK OF BEING TOO OPTIMISTIC I DON'T THINK WILL BE THAT DIFFICULT TO REPRODUCE PROVIDING NCI STAFF, PROVIDING THE DATA THAT WE ASKED FOR TO DO VARIOUS ANALYSES, BECAUSE FOR EVERY PROGRAM, ACTUALLY JIM WE DO HAVE IT BROKEN DOWN FOR ALL PROGRAMS THAT SUPPORT CLINICAL TRIALS. WITH OBVIOUSLY -- WE OBVIOUSLY DIDN'T PRESENT THAT IN FULL DETAIL BUT IT COULD BE DONE. NOW, THE BIG THING THAT'S THE UNKNOWN, AND THAT IS TRUE, IS THE PERCENTAGE OF THE VARIOUS GRANT PORTFOLIO, WE DID BREAK THOSE DOWN TO VARIOUS DIVISIONS AN PROGRAMS, THAT'S REALLY DEVOTED TO CLINICAL TRIALS, WE PROPOSED A METHODOLOGY WHERE PRINCE INVESTIGATORS PUT IN THEIR PROFESSION REPORT. APPROXIMATE PERCENTAGE. ZERO, 10, 25, 60, NOT 62.3, IN THEIR PROGRESS REPORTS FOR HOW MUCH WAS SPENT ON CLINICAL TRIALS. IF YOU WANTED TO DO IT ACCURATELY. AS PETER AND MITCH WERE POINTING OUT. THERE'S NO POINT DOING THIS ANALYSIS IF YOU'RE NOT GOING TO DO ANYTHING WITH THE DATA. BUT BASED ON DATA FROM 2006 YOU COULD MAKE SOME JUDGMENTS ABOUT THINGS YOU MIGHT DO IF THE DATA IN 2010 WERE THE SAME AND THEN WHAT YOU WANT TO DO IS REDO THE DATA WITHOUT MAKING PIs TURN IN THE PERCENTAGES AND SEE IF IT HAS LEGS. >> A THOUGHT, I'M NOT SURE SO MUCH WE NEED TO KNOW WHERE EVERY DOLLAR HAS GONE. WHAT I THINK THE STRATEGIC PLANNING COMMITTEE NEEDS TO KNOW IS HOW MANY PHASE 2s ARE FUNDED OUT THERE FOR BREAST CANCER? VERSUS WHAT IS GOING ON IN RARE TUMORS, NOT EVERY PENNY BUT WHAT IS GOING ON THROUGHOUT THE SYSTEM, BUT SYSTEM SETTING STRATEGIES FOR WHICH TRIALS ARE ABLE TO GO FORWARD WITHOUT KNOWING WHAT IS BEING DONE ON A DISEASE AND PHASE OF CLINICAL TRIAL LEVEL. THAT'S WHAT THEY REALLY NEED TO MAKE THEIR DECISION. IT'S ANOTHER ECONOMIC ANALYSIS TO LOOK AT IT'S WAY TOO EXPENSIVE TO DO A STUDY IN A CANCER CENTER VERSUS A GROUP. THAT'S A DIFFERENT THING. THAT RIGHT NOW MIGHT NOT BE SO NECESSARY. BUT WE NEED TO KNOW WHAT'S GETTING DONE. >> I THINK IT'S MORE FUNDAMENTAL THAN THAT. WE NEED A STRATEGY HOW WE LOOK AT THIS INFORMATION AND HOW ARE WE GOING TO MANAGE IT. WHAT WE HAVE -- WHEN WE HAVE THAT PLACE WE NEED UPDATEDDED DATA. -- UPDATED DATA. HOW MUCH DOES THIS COST? NOT CHEAP. SO UNTIL WE HAVE A STRATEGY TO DEAL WITH IT I DON'T THINK WE SHOULD NECESSARILY BURN THROUGH MORE RESOURCES WITHOUT KNOWING. HOW WE'RE GOING THE DEAL WITH IT. I AGREE, FULLY YES NEED TO KNOW WHERE WE ARE IN 2011 BUT WE DON'T NEED TO KNOW WHERE WE ARE FOR THE SAKE OF KNOWING WHERE WE ARE. WE NEED TO HAVE A PLAN HOW WE'RE GOING TO MANAGE IT. >> I THINK THE -- IT'S NOT EVERY DOLLAR BUT AS MITCH BROUGHT UP, WHAT ARE YOU DOING AFTER THE COOPERATIVE GROUPSCH WHAT I RECALL FROM THAT PRESENTATION, THERE WAS MONEY GOING TO DIFFERENCE AREAS I NEVER HEARD OF FOR CLINICAL TRIALS SO IT WOULD BE NICE TO KNOW WHEN MITCH MAKES THAT COMMENT WHAT ARE THE OTHER THAT FEED INTO CLINICAL TRIALS AN APPROXIMATE DOLLARS THAT ARE GO SOMETHING THAT WOULD BE USEFUL. AND MAYBE LIKE IN THE 2006 WOULD BE ENOUGH PETER AN SOMEONE CAN MAKE A COMMENT OF MAJOR CHANGES FROM THERE, JUST BIG PICTURE. >> SO TO MAKE A TANGIBLE SUGGESTION, PERHAPS WE CREATE A WORKING GROUP AROUND THE ISSUE TO DEVELOP A PLAN OF WHAT DATA IT NEEDS AND WHAT IT MIGHT DO WITH THE DATA, REPORT BACK TO THE GROUP IN TERMS OF NEXT STEPS THAT IT THINKS WOULD MAKE SENSE TO GO FORWARD (OFF MIC) [LAUGHTER] >> LET ME SUGGEST AN ALTERNATIVE TO THAT IS WE TAKE THIS DISCUSSION TO THE WORKING GROUP THAT WE CREATED, THE STRATEGIC GROUP, AND HAVE FURTHER DISCUSSION AROUND THIS IN TERMS OF GOING FORWARD. I THINK THIS ISSUE WAS CERTAINLY PART OF THE INITIAL THINKING OF THE SUBCOMMITTEE AND WHAT THE SECOND SUBCOMMITTEE WOULD DO. WE DIDN'T GO THERE FOR REASONS THAT JOEL HAS OUTLINED OF TRYING TO --hWE FELT THAT IT WAS MORE IMPORTANT TO LOOK AT FUNCTIONING OF THE SCIENTIFIC STEERING COMMITTEES AND A BROAD VIEW OF THE INTEGRATED NETWORK PORTFOLIO AS IT EMERGES. LET ME SUGGEST WE TAKE IT YOUR SUGGESTION BACK TO SUBCOMMITTEE, TALK ABOUT IT MORE AND SEE WHAT THE GROUP THINKS WE SHOULD DO. >> I THINK WE SHOULD REPRESENT THAT -- >> I THINK THAT WOULD BE INSTRUCTIVE EVEN IF WE DONE HAVE A SPECIFIC PLAN IN MIND YET WHAT WE'RE GOING TO DO WITH IT. WE HAVE ALLUDED TO IT IN VARIOUS WAYING IT'S NOT BAD TO UPDATE THE WHOLE -- SO WE'LL PUT THAT ON THE AGENDA FOR NEXT TIME. >> I WAS GOING TO SAY FOR THOSE THAT DIDN'T HEAR IT, PEOPLE LIKE TO SEE IT. >> I HAVE ONE COMMENT I THINK LONGER TERM EVALUATION EFFORTS ARE NECESSARY AND CRITICAL FOR THE LONG TERM HEALTH. AT THE SAME TIME I THINK THAT WE ALWAYS NEED TO HAVE A SAFETY VALVE FOR PLACES WHERE THINGS AREN'T WORKING RIGHT NOW. I PLACE THIS IN A COUPLE OF VENUES, I'M UNEASY IF SOMETHING IS REALLY NOT WORKING WELL RIGHT NOW, THERE DOESN'T SEEM TO BE A CLEAR PATH TO RESOLUTION. AND I'M WONDERING IF THAT'S SOMETHING YOU CAN TALK ABOUT OR IS THAT SOMETHING DISCUSSED ON A STEER I COMMITTEE CHAIR MEETING. >> SO THERE'S SPECIFIC ISSUES -- >> MAYBE A STEERING COMMITTEE IS HAVING PROBLEMS GETTING -- >> I DON'T KNOW IF EVERYBODY IS AWARE BUT STEERING COMMITTEE CHAIRS HAVE PERIODIC CONFERENCE CALLS. MAYOR THINGS WE DISCUSS THERE ARE ISSUES -- THINGS THAT ARE WORKING OR THINGS THAT AREN'T WORKING, WE TRY TO BRING THOSE UP. OTHERS MIGHT NOT NECESSARILY KNOW THOUGH THE NCI REPRESENTATIVES SHOULD KNOW THAT THERE ARE PROBLEMS THERE AND IT TAKES A WHILE FOR THE STEERING COMMITTEE TO GEL AND GET A SENSE OF WHAT THEY'RE DOING. BUT AT LEAST SOME OF THAT IS BEING APPROACHED AT THE STEERING COMMITTEE CHAIR MEETING. >> I HAVE A COMMENT TO THAT BECAUSE I THINK IT IS IMPORTANT TO MAKE SURE YOU'RE AWARE OF CONCERNS, SOMETHING IS NOT SHOWING AND (INAUDIBLE) WE WILL PERIODICALLY HAVE CALLS WITH SPECIFIC STEERING COMMITTEE ISSUES GETTING STARTED AND GETTING GOING (INAUDIBLE) SO I THINK COMMUNICATING BACK TO US THROUGH THE STEERING COMMITTEE LEADERSHIP I THINK IS VERY HELPFUL BECAUSE WE DO LISTEN TO THOSE COMMENTS. >> IN THE REPRESSION TO THE GROUP AND TO THE WORKING GROUP, IF -- IT WOULD BE INTERESTING IF THERE'S WAY TO GET AT THE FUNDS GOING TO CLINICAL TRIALS TO PREVENTION BECAUSE THAT REALLY IS AN UNMET NEED, IT'S HARD TO LEVERAGE SUPPORT FOR THAT, OTHER THINGS, WE WANT TO DO MORE TRANSLATIONAL SCIENTIFIC, GOOD TO GET A SENSE OF WHAT'S GOING ON THERE IN TERMS OF RESOURCES. >> OKAY. GREAT DISCUSSION. I THINK WE HAVE ONE MORE PRESENTATION BEFORE LUNCH BREAK. WE PUT THESE THREE PRESENTATIONS, THE OVERALL PRESENTATION OF THE RFA, DISCUSSION AB HOW WE'RE GOING TO OVERSEE THE PROCESS OF CREATING THE INTEGRATED NETWORK AND NOW WE WILL HAVE PRESENTATION FROM MIKE MONTELLO ON THE COMMON DATA MANAGEMENT SYSTEM FOR THE COOPERATIVE GROUPS, ANOTHER ESSENTIAL ELEMENT IN CREATING THIS INTEGRATED PROCESS. >> THANK YOU. GOOD MORNING. SO THE PREFACE OF OUR PRESENTATION IS TO PROVIDE A STATUS UPDATE REGARDING NCI INITIATIVE TO MODERNIZE A CRITICAL COMPONENT OF THE COOPERATIVE GROUP INFRASTRUCTURE THE CLINICAL DATA MANAGEMENT SYSTEM. OUTLINE BASED ON THE PRESENTATION WE BROKE OUT THREE AREA ESTABLISHING THE VISION FOR CDMS, OUR APPROACH THROUGH THE PROJECT AND THE PROJECT STATUS. THE VISION. JUST TO GET EVERYBODY ON THE SAME PAGE, WHAT ARE THE CLINICAL DATA MANAGEMENT SYSTEM AT CDMS? TOOLS AND PROCESSES THAT SUPPORT DATA COLLECTION, REMOTE DATA CAPTURE A TIP OF METHODOLOGY FOR DATA COLLECTION. DATA CODING, THE COMMON TOXICITY CRITERIA IS A GOOD EXAMPLE. DATA MANAGEMENT ACTIVITIES, YOU IDENTIFY DISCREPANCIES DELINQUENCIES, COMMUNICATION PROCESS, FIX THOSE ISSUES AND A CORRECTION PROCESS AND PREPARATION FOR THE DATA ANALYSIS. A CDMS DIRECTLY OR INDIRECTLY TOUCH IT IS ENTIRE ORGANIZATION. TOUCHES UPON SCIENTIFIC SAFETY, REGULATORY OPERATION OS FINANCIAL MANAGEMENT AND INDIVIDUALS IMPACTED INCLUDE THE GROUP CHAIR DOWN TO RESEARCH STAFF OUT IN THE FIELD AS WELL AS PATIENTS THEMSELVES. TYPES OF CDMS. THEY'RE TWO CAMPS. PAPER VERSUS ELECTRONIC. PAPER FORMS MAILED OR FAXED TO CORPORATE HEADQUARTERS AND OFTEN REQUIRES DOUBLE DATA ENTRY OR SCANNED IN USING TECHNOLOGY THAT'S AVAILABLE NOW USING (INDISCERNIBLE) OBJECT IDENTIFIER TECHNOLOGY INTO ELECTRONIC DATABASE. THE -- IT'S EASY TO SET UP. PAPER BASED FORM. CONS DOUBLE DATA ENTRY, DUMB FORMS REQUIRE MORE TIME AND EMPT TO COMPLETE, THE RISK OF DATA DISCREPANCY AND DELINQUENCY, ONCE THAT PAPER FORM IS OUT IN THE FIELD IT'S DIFFICULT TO MAKE SURE THEY HAVE THE LATEST VERSION IN THE FIELD. COMMUNE DAITION OCCURS OUTSIDE THE SYSTEM. WITH ELECTRONIC CMS THERE'S TWO FLAVORS HERE, YOU CAN HAVE HOME BUILT APPLICATIONS USING INTERNAL IT, COMMERCIAL OFF THE SHELF PRODUCTS USE VARIOUS PRODUCTS, VARIOUS VENDOR PRODUCTS THAT ARE AVAILABLE RIGHT NOW. THE PROS HERE, SIMPLIFIED VERSION CONTROL. SMART FORM SIMPLIFIED DATA COLLECTION, ONLY WOMEN CAN ASK THE QUESTION ABOUT PREGNANCY. THE FORM CAN AUTOMATICALLY DO IT FOR YOU. EDIT CHECKS TO E RE DEUCE DISCREPANCY DISCREPANCIES AND DELINQUENCIES. THE CON IT TAKES TIME AND EFFORT TO SET THESE THINGS UP. INSIDE A ELECTRONIC DATABASE. SO THE (INAUDIBLE) WITH CMS. AT ONE TIME ALL USED PAPER CDMS. THE COOPERATIVE GROUPS SHIFTED INDIVIDUALLY TO START UTILIZING ELECTRONIC CDMS. SOME DEVELOPED INTERNAL CUSTOM APPLICATIONS AND OTHER PROVIDE DIFFERENT VENDOR PRODUCTS. SOME STILL USE PAPER IN SOME CASES SO THIS CREATE AS LOT OF INTERAS WELL AS INTRA COMPAREN 'T WITH THAT ARE APPROACH TO CDMS. IN 2006 GROUPS THEMSELVES AGREED TO WORK TO IMPLEMENT BASICALLY A COMMON CDMS INFRASTRUCTURE, THEY DID INDEPENDENT ANALYSIS OF VARIOUS PRODUCTS AVAILABLE, THEY SELECTED THE DATA RAVE, IN 2009 CBIT HAD WHICH RESULTED IN META DATA. AND IN 2010 WE KICKED OFF THIS INITIATIVE TO ACCOMPLISH A COMMON CDMS FOR THE COOPERATIVE GROUPS. SO THE FACT THAT MULTIPLE CDMS ON COOPERATIVE GROUP DATA MANAGEMENT SYSTEM. IT IS NECESSARY FOR PERFORMING CLINICAL TRIALS. IT IS THE MEANS AND NOT THE END OF WHAT WE TRY TO DO. SOMETIMES THE INEFFICIENCIES OF THE PROCESS CREATE DISTRACTIONSES TO SCIENTIFIC OBJECTIVES. SO WITH THIS INITIATIVE WE HOPE TO REINFORCE SCIENCE AND PATIENT BY OPTIMIZING EFFICIENCY AND EFFECT TICHNESS -- EFFECTIVENESS OF DATA MANAGE SYSTEMS AND PROCESSES. WE TRY TO INCREASE -- THE INEFFICIENCIES RESULT IN INCREASED TRAINING COST, INCREASED RISK OF DATA DISCREPANCIES AN DELINQUENCIES WHICH RESULTS IN TIME AND EFFORT TO CORRECT AND COMPLETE THOSE ISSUES. AND THEN DELAYS TO ATTAIN SCIENTIFIC RESULTS OF THE STUDY. SO THAT ENABLES REINFORCED BY THE IOM REPORT WHICH IDENTIFY THE ADOPTION OF A COMMON ELECTRONIC REGISTRATION DATA CAPTURE SYSTEM TO INCREASE THE CONSISTENT ACROSS CLINICAL TRIALS BY CON SERK RESOURCES, WE DO SEE WORK WITH PATIENT ENROLLMENT AND FOLLOW-UP, MORE TIMELY REVIEW OF DATA MANAGEMENT ON TRIAL, ENHANCING KNOWLEDGE GAINED AND STANDARDIZING CASE REPORT FORMS TO EASE THE BURDEN OF REGULATORY OVERSIGHT AND LEAD TO BETTER COMPLIANCE IN TRIALS. SO THE OPPORTUNITY, THE OPPORTUNITIES HAVE ALWAYS BEEN THERE. OUR INVESTIGATORS HAVE MULTIPLE COOPERATIVE GROUPS AND THROUGH THE CTSU WHICH ALLOW GROUPS MEMBERSHIP TO PARTICIPATE ON EACH OTHER'S CLINICAL TRIALS. THERE'S ADDEDDED EMPHASIS NOW, OBVIOUSLY WE'RE ASKED TO DO MORE WITH LESS, FUNDING CONSTRAINTS NOW REQUIRES IMPROVING OUR EFFICIENCY AND THE TRANSFORMATION ACTIVITIES TALKED ABOUT EARLIER ARE ALSO A STIMULUS FOR FURTHER PROMOTION OF NETWORK COLLABORATION AND AS THESE GROUPS COME TOGETHER THEY INDIVIDUALLY HAVE TO DETERMINE WHAT IS GOING TO BE THEIR COMMENT -- COMMON NETWORK GROUP CDMS SO WHY NOT USE THE ENTIRE NETWORK ACROSS THE BOARD. SO THE VISION FOR COMMON COOPERATIVE GROUP CDMS. REINFORCE THE FOCUS ON ZYSCIENCE AND PATIENT, NOT DATA MANAGEMENT. PROMOTE EFFICIENT ACCURATE DATA ENTRY USING A USER FRIENDLY INTERFACE. MAKE SURE IT'S SCALED FORIUS ACROSS ALL COOPERATIVE GROUP CLINICAL TRIALS, THE VARIOUS DIFFERENT FLAIRS OF TREATMENT TRIAL, PREVENTION TRIALS, CONTROL AS WELL AS DIAGNOSTIC STRIELS. WE WANT TO -- TRIALS. WE WANT TO MINIMIZE TRAINING ACROSS THE GROUPS TO SHARED TRAINING AND EXPERIENCES. AND REDUCE THE BURDEN COSTS NOT ONLY COOPERATIVE GROUP OPERATION OFFICES BUT ALSO OUT IN THE FIELD. THE PROJECT ORGANIZATION OR APPROACH. FIVE THINGS NEED TO COME TOGETHER FOR THIS PROJECT TO BE SUCCESSFUL. WE NEED A STANDARDIZED APPROACH TO THE APPLICATION THAT'S DONE, WE PURCHASE META DATA. THAT'S COMPLETE. CORPORATE CONFIGURATION, THESE ARE HIGHLY ADAPTABLE. YOU CAN SET IT UP IN A WAY THAT ORGANIZATION A LOOKS DIFFERENT THAN ORGANIZATION B SO WE HAD TO COME ONE A COMMON CORE CONFIGURATION. DONE. BUSINESS PRACTICES, THERE'S A LOT OF BUSINESS PRACTICES THAT ARE TIED TO THE CDMS SUCH AS DATA DELINQUENCY RULES. ONE COOPERATIVE GROUP HAS POLICIES THAT DATA IS DUE AT 14 CALENDAR DAYS. SHE HAD 10 WORKING DAYS, A THIRD HAS 15th AND 30th OF THE MONTH. THOSE SIMPLE ISSUES TOGETHER AND HAVE A COMMON APPROACH TYPE OF THING WOULD MAKE LIFE EASIER FOR PEOPLE IN THE FIELD. WANT ?IERK THERE'S A COMMON INTEGRATION TOUCH POINTS WITH GLOBAL APPLICATIONS. THERE'S CERTAIN APPLICATIONS. PATIENT ENROLLMENT SYSTEM, NCI ACCRUAL REPORTS, ADVERSE EVENT REPORTING SYSTEMS. ONE TIME APPROACH THAT MEETS THOSE NEEDS. WE EMPHASIZE, WE RECOGNIZE VERY EARLY WE WANT TO HAVE A COMMON SINGLE SIGN-ON ACROSS THE BOARD. SO INVESTIGATOR FROM -- CAN SIGN ON TO A COG STUDY USING THE SAME USER NAME AND PASSWORD THROUGHOUT. WE THOUGHT THAT WAS IMPORTANT FOR THE SUCCESS OF THE OVERALL PROJECT. FINALLY COMMON CASE REPORT FORMS. AND WE'LL LEVERAGE THE CDSR, CRF LIBRARY. SO WHILE EVERYONE APPRECIATES THE NEED FOR STANDARDIZATION THERE IS ALWAYS THE FEAR THAT WITHIN ORGANIZATION ESPECIALLY THE GOVERNMENT, WILL GO TOO FAR TRYING TO BUILD A STANDARDIZED ONE SIZE FITS ALL APPROACH FOR EVERYBODY. THROUGH THE GROUP CDMS INITIATIVE WE'RE THOUGHTFUL HOW WHEN AND WHERE WE STANDARDIZE. WE'RE RESPECTFUL ABOUT DIFFERENCES BETWEEN THE COOPERATIVE GROUPS AN UNIQUENESS OF THE THE SCIENCE OF EACH INDIVIDUAL TRIAL. WE SEEK TO PROMOTE EFFICIENCY ALLOWING THE NECESSARY FLEXIBILITY REQUIRED TO SUPPORT THE DIFFERENCES BETWEEN RADIATION, SURGERY, PREVENTION, IMAGING, AND PEDIATRIC TRIALS. SO AS THE SLIDE DEMONSTRATES WE ALLOW SOME LEVEL OF BRANDING AND CUSTOMIZATION NECESSARY TO CAUSE UNIQUENESS OF THEIR ORGANIZATION AND SCIENTIFIC PURSUITS. BUT TO PROMOTE EFFICIENCY WE NEED A COMMON INFRASTRUCTURE. WHETHER A RESEARCH NURSE IS WEARING COG SWAB, THEY KNOW HOW TO FIT THE CAP BECAUSE OF THE USE OF COMMON INFRASTRUCTURE. THE STRAP ON THE BACK OF THE CAP. SO ACROSS THE CDMS IS THE SAME. WE ALLOW CUSTOMIZATION NECESSARY TO SUPPORT -- BUILDING A COMMON BACKBONE TO PROMOTE EFFICIENCY AND EASE DATA MANAGEMENT BURDEN ON LOCAL ORGANIZATIONS AS WELL AS COOPERATIVE GROUPS CORPORATELY. SO KEY CONCEPTS FOR SUCCESSFUL DEPLOYMENT. META DATA HAS A LOT OF EXPERIENCE WITH THEIR PARTICULAR PRODUCT AND COOPERATIVE GROUPS HAVE GENERATIONS OF EXPERIENCE IN THIS AREA. OFTEN IT'S GENERAL EXPERIENCE WITH CDMS ACTIVITIES. WE HAVE A COUPLE OF GROUPS THAT HAVE SPECIFIC KNOWLEDGE AS WE SPEAK. THE ALLIANCE ARE MORE SPECIFICALLY MAYO HAVE TWO YEARS EXPERIENCE UTILIZING META DATA AND NCI'S DATA OUR CANADIAN BRETHREN HAS OVER FIVE YEARS EXPERIENCE. SO THE STRIVE FOR THE FEATURES, WE WANT TO MAKE SURE WE HAVE STANDARDS IN PLACES A STANDARD APPROACH TO THEM AND COMMUNICATION IS EMPHASIZED THROUGHOUT. SO THE CAP. WE HAVE ADOPTING OORGSES, THE NATIONAL -- ORGANIZATIONS THE NATIONAL CANCER INSTITUTE AS WELL AS CONTRACTORS SUPPORTING THEM. THE ORGANIZATIONS ADOPTING THE COMMON CDMS IS ALL THE COOPERATIVE GROUPS BUT NOT LIMITED TO THE COOPERATIVE GROUPS. WE HAVE THE PHASE 1 CONSORTIUM, AS WELL AS TWO OF OUR NCI CONTRACTORS. (INAUDIBLE) CTSU. THE ROLE OF EACH ONE OF THESE INDIVIDUAL ORGANIZATIONS, TO MODIFY INTERNAL BUSINESS AND OPERATIONAL TECHNICAL INFRASTRUCTURE TO SUPPORTo THE TRANSFORMATION. PARTICIPATE IN STANDARDS DEVELOPMENT AND ADOPTION ACTIVITIES, INTEGRATE THEIR LOCAL APPLICATIONS AND ALSO PARTICIPATE LOCAL KNOWLEDGE OR TRAINING ACQUISITION ACTIVITIES. THE NCI, THIS IS A TRANS-NCI INITIATIVE T. ROLE IS TO PROVIDE OVERSIGHT TO ESTABLISH THE OVERALL DIRECTION AND EXPECTATION FOR THE PROJECT. TRY TO PROMOTE STANDARDIZATION, NOT STANDARDS, WITHIN THE NCI, WE DONE CARE 14 CALENDAR DAYS OR TEN WORKING DAYS, PIG ONE AND LET'S G FORWARD WIT. AND RESPONSIBLE FOR RESOURCE ALLOCATION, THE HOSTING, TRAINING, ET CETERA. WE HAVE A VARIETY OF CONTRACTORS PROVIDING SUPPORT TO THE INITIATIVE. THE CTSU AND THE COOPERATIVE GROUPS. WE'LL TALK ABOUT MORE AND THE SUPPORT CENTER IN A SECOND BUT ALSO RESPONSIBLE FOR IC INTEGRATION ACTIVITIES, TRAINING FUNDING AN LOGISTICAL SUPPORT. CAPITAL TECHNOLOGY AND INFORMATION SYSTEMS PROVIDE IT INTEGRATIONS FOR CTEP APPLICATIONS. ETHICS PROVIDES WORKING GROUP LEADS FOR SEVERAL COMMITTEES AND MAKE SURE WE'RE STAYING IN CONJUNCTION WITH THE CBIT ACTIVITIES ONGOING AND FINALLY META DATA USING THEIR PRODUCTS, HOSTING, TRANSFER, ET CETERA. CDMS SUPPORT CENTER IS LOCATED WITHIN THE CTSU, IT HAS REPRESENTATION FROM ALL THE MAJOR PARTIES AND THE ROLE IS CENTRAL MANAGEMENT NCI IMPLEMENTATION OF META DATA, COORDINATING EFFORTS TO MAKE SURE WE HAVE A UNIFORM DEPLOYMENT. PROVIDING OVERSIGHT FOR THE DAY TO DAY ACTIVITIES AND COORDINATING THE VARIOUS DIFFERENT WORKING GROUPS AN TRAINING ACTIVITIES. SO AS I SAID BEFORE, WE HAVE A BALANCING ACT. TRYING TO MEET THE NEEDS OF THE NETWORK AT THE SAME TIME NOT DISRUPTING WITHIN THE LOCAL ORGANIZATION. SO HOW DO WE DO IS THAT USE WORKING GROUPS TO IDENTIFY STANDARDS AND BEST BUSINESS PRACTICES. MORE DETAIL ABOUT THOSE IN A SECOND SO I'LL SKIP OVER THOSE QUICKLY. WE STARTED KICKING OFF THE LAST MONTH OR TWO REGARDING METRICS, REMOTE CEAT CAPTURE TRAINING AS WELL AS AUDITING. AND KICKED OFF IN 2012 WHICH WILL FOCUS IN ON REPORTING, STAT ISSUES SUCH AS NAILSIS AS WELL AS ANCILLARY STUDIES. SO GOVERNANCE, COORDINATORS FACILITATED, ONE IS A COOPERATIVE GROUP MEMBER. WE HAVE INDIVIDUAL GROUP CHARTERS THAT DEFINE THE GOVERNANCE GOALS AND DELIVERABLES TO MAKE SURE EVERYBODY IS ON THE SAME PAGE TRYING TO ACCOMPLISH EACH WORKING GROUP. EACH HAS ONE VOTING GROUP TO MAKE RECOMMENDATIONS ON BEHALF OF THEIR ORGANIZATION AND THE MEMBERSHIP FOR ALL THE WORKING GROUPS WE HAVE AT LEAST TWO NCI REPS, TWO CTSU REPS AND ONE OR MORE FROM EACH OF THE OTHER COOPERATIVE GROUPSCH COMMUNICATION PLAN. WE GET THE WORD OUT THROUGH THE WORKING GROUPS, LEADERSHIP COMMITTEE, TRAINING AS WELL AS MONTHLY NEWS LETTER GOES OUT AS AS WELL AS COOP ATTRACTIVE GROUP LEADERSHIP. STATUS UPDATE. I DON'T ANTICIPATE ANYBODY WILL BE ABLE TO READ THE SLIDE BUT WE HAVE A PROJECT PLAN AND TIME LINE, THIS OUTLINES THE MAJOR DELIVERABLES FOR THE PROJECT AND HOW IT WILL COME TOGETHER. EACH ONE OF THESE MAJOR DELIVERABLES WE HAVE A SPREADSHEET BEHIND IT SO WE HAVE TO HAVE A REAM OF PAPER THAT SHOWS WHERE THE VARIOUS PROJECT PLANS ARE AND MAKING SURE WE'RE NOT MISSING GAPS ALONG THE WAY. THE GROUP DEPLOYMENT PLAN. WE STARTED APRIL OF THIS YEAR, WE BROKE IT OUT IN THREE STAGES AN EEF STAGE WE HAVE THREE OR FOUR DIFFERENT COOPERATIVE GROUPS PARTICIPATING WITH THE OTHER ORGANIZATIONS PARTICIPATING. THE FIRST GROUPS ARE ALPHA STAGE, KICKED OFF IN APRIL OF THIS YEAR, WE GAVE THEM ONE YEAR TO IMPLEMENT META DATA WAVE. STAGE 2 STARTED IN JULY OF THIS YEAR, BRAVO NOW HAS ALSO NINE MONTHS AND THEN THE TROLLY STAGE STARTING OCTOBER. SO THE END RESULT IS TARGETED COMPLETION FOR ALPHA AND BRAVO IS MARCH OF NEXT YEAR AND CHARLIE BY JUNE OF NEXT YEAR. SO BASICALLY BY THE EARLY SUMMER OF 2012, ALL NEW COOPERATIVE GROUP TRIALS WILL BE UTILIZING META DATA FOR DATA MANAGEMENT. NCI TRAINING SUPPORT FOR THE META DATA DEEMPLOYMENT. META DATA RAVE HAS -- IT'S UNBELIEVABLE. PARTICULAR APPLICATION. THEY'RE AVAILABLE ONLINE AS WELL AS FACE TO FACE. WE'RE TAKING THE TRAINER TYPE OF PHILOSOPHIES IDENTIFYING A CORE GROUP WITHIN EACH COOPERATIVE GROUP TO BE TRAINED AND THEY CAN PASS THE INFORMATION DOWN. THE NCI FOR THE CTSU PROVIDES SUPPORT INCLUDING SCHEDULING IMPLEMENTATIONS AND ET CETERA. TRAVEL TRAINING COSTS FOR THE PUND MENTAL AND MID LEVEL COURSES WE TRY TO IDENTIFY 200 INDIVIDUALS THAT WE -- GET THAT TRAINING AND 100 FOR THE ADVANCED TRAINING. AND ADDITIONAL TRAINING SESSIONS CAN BE MADE AVAILABLE. THE STATUS OF THE VARIOUS WORKING GROUPS. THE DATA ELEMENTS WORKING GROUP. WE HAVE ESTABLISHED A CASE REPORT AND GOVERNANCE MODULE FOR THE -- COMMUNICATION IDENTIFY ENHANCEMENTS TO IMPROVE THAT COMMUNICATION BETWEEN META DATA RAVE AND THE CADSR. THE DATA QUALITY WORKING GROUP, CASE REPORT FORM QUERY TIMELINESS AND PROVIDE RECOMMENDATIONS FOR CLASSIFYING PROTOCOL DEVIATION. STUDY CONCEPT, WE IDENTIFY STANDARD PROCEDURES AND COMMUNICATION PROCESSES AND STANDARD PROCESS FOR LOSS TO FOLLOW-UP AS WELL AS (INAUDIBLE). DESIGNING STANDARD META DATA RACE SPECIFIC STUDY WORK FLOW, OPTIMAL METHODS FOR DESIGNS INSIDE META DATA. WE HAVE RECENT VALIDATION TEST CASES, WE ALSO PERFORMED TWO SIDE AUDITS ONE TWO WEEKS AGO AND ONE NEXT WEEK, MOST OTHER THINGS THEY'RE DOING IS CONFIRMING META DATA DISASTER RECOVERY SECURITY AND BACK UP PROCEDURES TO MAKE SURE THEY'RE ALL UP TO SNUFF. CORE CONFIGURATION, WE CREATED A DOCUMENT, A STANDARD META DATA REAF FOR CONSIDERATION ACROSS THE SYSTEM. NO MORE DIFFERENT INTEGRATION ACTIVITIES TO COME TO FRUITION FOR THIS PROJECT TO BE SUCCESSFUL. PRIOR TO ONES NECESSARY PRIOR TO BE IMPLEMENTED, FIRST WE HAVE TO MAKE SURE CADSR (INAUDIBLE) CASE REPORT FORMS IS RESOLVED. AGAIN, TO EMPHASIZE WE CLEARLY RECOGNIZE THAT THE IMPORTANCE OF SINGLE SIGN ON TO MAKE THIS WORK. THE THREE APPLICATIONS YOU SEE HERE, THESE ARE APPLICATIONS THAT COOPERATIVE GROUPS HAVE BEEN USING FOR MANY, MANY, MANY YEARS, UP TO A DECADE SO WHAT HE EAR TRYING TO DO IS LEVERAGE THE CURRENT INFRASTRUCTURE WE HAVE AND BASICALLY TIE IT IN TO META DATA REAF TO MAKE IT SIMPLER TO USE THAT PARTICULAR AMPLYCATION. THE PRIORITY TWO ISSUES WILL BE DEPLOYED WITHIN THE FIRST SIX MONTHS, THE LATER HALF OF 2012. THE NCI SUPPORTS AN CIS THINGS LIKE THAT AS WELL AS SERIOUS EVENT REPORTING WHICH WE'LL TALK MORE ABOUT IN A SECOND. AND PROBABLY 2013 WHICH INCLUDE AUDITING AND FURTHER EXPANSION OF NCI REPORTS. SEVERE ADVERSE EVENT REPORTING, ONE CLEAR EXAMPLE OF HAVING COMMON CDMS AND HOW IT BENEFITS THE ONCOLOGY COMMUNITY. CURRENTLY WE HAVE A PROBLEM. THERE'S A DISCONNECT BETWEEN ADVERSE EVENT REPORTING AND SEVERE. ROUTINE EVENTS AND SEVERE AD VER EVENTS ARE CAPTURED IN SEPARATE SYSTEMS. YOU HAVE DOUBLE DATA ENTRY, DOUBLE DATA ENTRY YOU HAVE DISCREPANCIES WHICH REQUIRE RECONCILIATION, THIS PROMOATS A FAIR AMOUNT OF UNDERREPORTING OR OVERREPORTING. THE APPROACHED SOLVED THESE PARTICULAR ISSUES HAVING A SINGLE SOURCE FOR REPORTING ROUTINE AND SEVERE ADVERSE EVENTS. LET'S TAKE ADVANTAGE OF WHAT WE HAVE INSIDE OF RAVE. WE ENTER ONE TIME WITHIN RAVE WHICH REDUCES DATA DISCREPANCIES BY DEFINITION ENTRY. SMART CRS BASICALLY IDENTIFY WHICH EVENTS REQUIRE ADDITIONAL INFORMATION AND RESEARCH DONE ON THAT INFORMATION, SAYS THIS IS A SEVERE ADVERSE EVENT, OPENS UP ANOTHER PAGE, REQUIRE ACE DITIONAL INFORMATION FOR THAT PARTICULAR ADVERSE EVENT TO BE POPULATED. REDUCE THE TRAINING REQUIREMENTS ACROSS THE ONCOLOGY COMMUNITY. IMPLEMENTATION SUPPORT. ONCE IT'S DEPLOYED WE DON'T TURN AWAY AND TELL THE COOPERATIVE GROUPS GOOD LUCK. WE STICK AROUND. WE PROVIDE A FORM TO SHARE EXPERIENCES, WITH TELECOM AND FACE TO FACE MEETINGS. SPANNING EFFORTS, THE OTHER ISSUES, PROCUREMENT ISSUES, HOSTING ANCILLARY SOFTWARE MAYBE PROCURED IN THE FUTURE AS WE GO FORWARD. AND POTENTIAL EXPANSION OF PROJECT TO ADDITIONAL ADOPTING MULTI-SENSOR@7o ORGANIZATION. POTENTIAL EXAMPLES WILL BE DCP AND CTEP PHASE 2 CONTRACTS OR THE PEDIATRIC BRAIN CONSORTIUM. IN CONCLUSION A MODERNIZED STANDARDIZED COOPERATIVE GROUPS CLINICAL DATA MANAGEMENT SYSTEM WILL SUPPORT AND COMPLIMENT THE TRANSFORMATION OF THE COP COOPERATIVE GROUPS INTO A NETWORK. YOU WILL MEET FDA AND OTHER ELECTRONIC REQUIREMENTS FOR CAPTURE SECURITY AND TRANSFER. WE RE DEUCE EFFORT AND COST FOR DATA MANAGEMENT, IMPROVE TRIAL MLGMENT AND DECISION MAKING, PROMOTE DATA SHARING AND SETS THE STAGE FOR FURTHER INFRASTRUCTURE IMPROVEMENTS AS WE LOOK FORWARD. ONE EXAMPLE, REMOTE AUDITING AND SOMETHING IN THE FUTURE TO THINK ABOUT. SO QUESTIONS TO TOSS OUT, I KNOW YOU HAVE QUESTIONS FOR ME BUT I'LL TOSS QUESTIONS TO YOU FIRST. DO YOU0nn HAVE SUGGESTIONS HOW TO BEST PROMOTE DEPLOYMENT OUT TO THE COOPERATIVE GROUP? RIGHT NOW WE'RE FOCUSING ON LEADER SHIP, HOW TO GET THE WORD OUT TO THE ONCOLOGY COMMUNITY. IF, WHEN, HOW. DO WE EXPAND TO THE OTHER COOPERATIVE GROUPS AND OTHER PLAYERS CURRENTLY AND GIVEN THE METRICS KICK AWFD, ANY METRICS OR STEPS WE SHOULD BE THINKINGN'T TO MEASURE HOW WE -- COMPARED TO HOW WE ARE NOW TO IN THE FUTURE TO CONNING TO IMPROVE THE PROCESS AS WE MOVE FORWARD. QUESTIONS? >> THANK YOU. WE CAN OPEN UP FOR SOME QUESTIONS OR DISCUSSION. >> GREAT. I WAS JUST WONDERING, HAVING NOT HAD THE OPPORTUNITY TO WRITE A PHASE 3 TRIAL IN A PHASE 3 TRIAL REPORT OR PRESENTATION FROM THE GROUP. SO HOW MANY -- I'M AN INVESTIGATOR, AND I WANT TO WRITE THE TRIAL THAT I JUST COMPLETED. SO HOW DOES IT WORK NOW IN TERMS OF ME MINING THE DATA FOR MY PRESENTATION REPORTING DATA SHARING OVER HERE AND HOW IT WILL WORK IN THIS SYSTEM. WILL THIS SYSTEM SHOREN THE TIME IT TAKES TO GET THE DATA TO MAKE THE PRESENTATION, ET CETERA? >> THAT WOULD BE OUR HOPE. HOW WE DO IT NOW T SHORT ANSWER IS 100 DIFFERENT WAYS. MOVING FORWARD, WE HAVE ONE UNIFIED WAY OF DOING THAT. I THINK ONE THING THAT'S BEING TRYING TO PROMOTE LOOKING FOR EFFICIENCY, HOPE TO GARN INEFFICIENCIES BY HAVING THESE STANDARDS. ALSO BY ESTABLISHING THIS WORKING GROUP AS WE GO FORWARD, BASICALLY -- OOPS SORRY. A FORUM TO SHARE EXPERIENCES, THOSE WHICH ACTUALLY ARE DOING BETTER AT SOME ACTIVITIES CAN SHARE THAT EXPERIENCE WITH OTHER GROUPS TO MAKE SURE WE CAN BUILD UPON THOSE THINGS AN THOSE GROUPS WHO ARE STRUGGLING CAN SAY HOW DO YOU DO? AND WE CAN AS A GROUP COME TOGETHER AND IMPROVE THE PROCESS. >> YOU HAVE ONE INDIVIDUAL THAT THE INVESTIGATOR WILL CONTACT AND OTHER DATA WILL COME. >> WE'RE NOT DOWN TO THAT LEVEL HOW TO PEOPLE UTILIZE THE TOOL BUT AN ORGANIZATION HAS ONE GO TO PERSON, YOU MAY HAVE A TEAM OF GO TO PEOPLE AND THAT REALLY IS THE INDIVIDUAL DECISION OF EACH COOPERATIVE GROUP. BUT UTILIZE THE TOOL, LET'S NOT OVERSELL THIS, INITIAL TRANSFORMATION STAGES, WHEN ANYTHING NEW THIS IS PROBABLY INEFFICIENCIES THAT CAUSES THAT BUT OVER TIME WE DO ANTICIPATE WE'LL SEE IMPROVED EFFICIENCIES AND GET TO YOUR DATA WHEN YOU NEED IT ADS QUICKLY AS YOU NEED IT. >> SO A A LAUDABLE GOAL TO HAVE NEW TRIALS STARTING SUMMER OF 2012 COME UP IN THE SYSTEM, CAN YOU SHARE WITH US -- I SHOULD KNOW THIS BUT I CAN'T RECALL, THE PLANS FOR PILOTING THIS IN ONE OR MORE COOPERATIVE GROUPS. >> THAT'S A HARD ONE TO ANSWER. THE EXPERIENCE WE HAVE WITH META DATA WORKING WITH THE COOPERATIVE GROUPS, WE HAVEN'T IDENTIFIED -- THAT TIME LINE LAID OUT, IF WE RUN INTO ISSUES WE HAVE TO TAKE A STEP BACK. >> JUST SO I UNDERSTAND, THERE'S NO PLAN TO PILOT -- >> THAT IS TRUE SIR. I YIELD TO DAN. >> THANK YOU. SO THE EXPERIENCE WE HAVE -- THANK YOU, DR. ABRAMS, GETS ME OUT OF MY LITTLE BIND THERE. WE HAVE EXPERIENCE OF NCIC AS WELL AS THE AALLIANCE WHO ARE -- THANK YOU. I CAN BETTER -- THAT'S A BETTER ANSWER THAN THE ONE I HAD. >> FIRST I WANT TO THANK NCI AND MIKE IN PARTICULAR, THIS IS A REALLY POSITIVE PROJECT. AT LEAST FROM OUR PERSPECTIVE FROM THE ALLIANCE THAT IT HAS BEEN A TRUE PARTNERSHIP. AND BACK AND FORTH GIVE AND TAKE, AND GOOD PROGRESS BEING MADE ON BOTH SIDES. I THINK THIS IS REALLY GONE VERY WELL. IT IS NOT BEEN EASY AT ALL. IT'S VERY, VERY HARD WORK AND THE SAVINGS IN THE CENTRAL OFFICE ARE GOING TO COME YEARS DOWN THE LINE. THEY'RE GOING TO COME AT THE TIME OF ANALYSIS, NOT AS THE -- SO WE'RE PUTTING UP TRIALS RIGHT NOW THAT'S GOING THE TAKE THREE YEARS TO ENROLL PATIENTS AND THEN WE HAVE TO FOLLOW THEM. THEN THE BEAUTY OF THE SYSTEM IS THE DATA WILL BE GOOD AND CLEAN AND READY TO GO BUT THAT SAVINGS IS GOING TO TAKE QUITE A LONG TIME. I WOULD BE INTERESTED IN THE METRICS OF SUCCESS INTERESTED IN TIME SAVING ATJ2 THE LOCAL SITE. THAT IS WHAT WE CAN ALSO GET, WHEN LOCAL SITES HAVE ONE SYSTEM TO LEARN AND THEY CAN ENTER THE DATA AND HAVE QUERIES BACK TO THEM AND GET THAT DATA CLEAN BUT WE NEED TO GATHER BASELINE DATA ON THAT RIGHT NOW BEFORE THE SYSTEM GOES INTO PLACE. SO I WOULD BE INTERESTED COLLECTING WORKLOAD AND TIME PRETRICK INFORMATION AT PARTICIPATING SITES TO COMPARE IN THREE YEARS, AND FIVE YEARS TO QUANTIFY THOSE SAVINGS. THAT'S WHERE THE GREATEST SAVINGS WILL COME, THAT WAS OUR GOAL TO SIMPLIFY THINGS FOR THE SITE. WE HAVE THREE TRIALS UP IN THE ALLIANCE, THERE'S ONE CLGB LEGACY, ONE CENTRAL LEGACY. AND THE SITES LIKE THE SYSTEM. IT IS TAKING MORE TIME TO PUT STUDIES UP, THAT'S NOT JUST RAVE'S FAULT. THE COMPREHENSIVE SYSTEM IS GOING TO REQUIRE THAT. WITH REGARD TO NOT THE SPECIFICS OF RAVE BUT WHAT IT TAKES TO BE A 21 CFR-11 COMPLIANT SYSTEM. THAT REQUIRES ENHANCED LEVEL OF DOCUMENTATION, TESTING COMPARED TO ANYTHING YOU HAVE EVER DONE BEFORE. THE RIGHT THING TO DO BUT IT IS A TIME COMMITMENT THAT WE HAVEN'T HAD TO DO IN THE PAST. RIGHT NOW IT'S TAKING US THREE TO FOUR MONTHS PER STUDY TO GET THEM UP AND READY. WHERE THE ARRA SYSTEM COULD UP IN A FEW WEEKS. IT IS TAKING LONGER BUT THAT WILL GET FASTER AS WE DEVELOP OUR GLOBAL LIBRARY AND WE DEVELOPED THE CUSTOM FUNCTIONS WHICH ARE USABLE. I'M PROBABLY GETTING TOO TECHNICAL HERE BUT IT IS A REAL LEARNING CURVE AND ALL TRIALS BY ALL GROUPS IS HIGHLY AMBITIOUS AND I THINK WE CAN TRY. WE WILL MAKE THAT IN LINE BUT WE STARTED A LONG TIME -- >> WE RECOGNIZE THAT. WE HAVE TO RECOGNIZE (INAUDIBLE) AN IMPORTANT THING AND RIGHT NOW TO THIS POINT IN TIME, WE ACTUALLY HAD A RELEASE ON MONDAY, WE ARE STILL ON STRIDE TO MEET OUR APRIL AND JUNE DEADLINES. I'M NOT SAYING THAT SOMETHING WILL HAPPEN IN JANUARY OR FEBRUARY, WHEN THINGS GET CLOSER BUT RIGHT NOW WE ARE STILL MARCHING FORWARD AND THOSE DELIVERY DATES ACROSS THE PROGRAM BECAUSE WE WILL BE ABLE TO MEET THEM. >> SO THE SYSTEM NOW AND PERCEIVABLE FUTURE COMMUNICATED WITH THE MORE COMMON ELECTRONIC HEALTH RECORD PLATFORMS. >> WE ACTUALLY HAVE PART OF OUR DISCUSSION WE PICKED UP OUR AUDITING TEAM MEETING LAST WEEK AND THAT WAS ONE OF THE DISCUSSIONS. IT DOESN'T DO THAT INHERENTLY NOW BUT HAD THE COMMON CDMS WILL ALLOW US TO BUILD OUT THOSE CONNECTIVITY ISSUES IN THE FUTURE, IT WON'T HAPPEN NEXT YEAR BUT ALLOWS US TO THINK ABOUT THOSE ISSUES AN APPROACHES GOING FORWARD. >> SO THIS IS A QUESTION FOR DAN. TO CLARIFY, AS AN ESTIMATE YOU THINK IT'S SOMEWHERE BETWEEN 2 TO 3 TIMES AS LONG TO GET A STUDY UP AND RUNNING AT LEAST WHEN YOU START? >> YES. >> THAT'S GOOD TO KNOW. >> THE FIRST TRIALS GOING UP, BASICALLY INFORMATION THEY PROVIDED TO US IS TYPICALLY SITES MAY TAKE TWO MONTHS TO GET TRIALS SET UP, WITH THE META DATA RAVE THE INITIAL TRIAL TAKE 3-S TO 4 MONTHS. THE SECOND TRIAL MAY TAKE 3 MONTHS, SO ON, P AND HOPEFULLY IMPROVE OVER TIME. WE ANTICIPATE THING ALSO IMPROVE OVER TIME. >> I HAVE A REALLY BASIC QUESTION. DO YOU ENVISION THIS A PAPER LESS SYSTEM? >> BY DESIGN, YES. BY DEFINITION. YES. >> THAT'S REALLY COOL. FROM THE DATA ANALYSIS PERSPECTIVE, JUST FROM MONITORING AUDITING THE QUALITY OF THE TRIAL. >> FROM START TO FINISH THIS SHOULD BE PAINLESS. THAT IS A GOAL WHICH WE THINK -- BACK END ISSUE AS WELL AS FRONT END ISSUE SHOULD SIMPLIFY THINGS A LOT. SO THE TIME AND EFFORT THAT DAN, JUST TO EMPHASIZE, MAYBE TAKING MORE TIME TO GET THE STUDY SET UP BUT THE BANG FOR YOUR BUCK LONG TERM DATA MANAGEMENT ACTIVITIES AND ANALYSIS IT'S WORTH THE INVESTMENT TO GET IT RIGHT AND SET UP IN THE ELECTRONIC SYSTEM. YOU CAN SET IT UP IN A PAPER BASED SYSTEM IN A MONTH AND A HALF BUT YOU HAVE STRUGGLES AN INEFFICIENCIES THAT OCCUR LATE WE ARE THE DATA MANAGEMENT ACTIVITIES AND DATA ANALYSIS ACTIVITIES LATER ON. >> ONE MORE COMMENT IN THAT REGARD. WHAT WE HAVE FOUND ACTUALLY IS THAT THE RIGOR OF PUTTING IT UP IN RAVE MADE THE PROTOCOL CLEANER WHEN WE OPEN IT. AND I EXPECT WILL RESULT IN FEWER PROTOCOL AMENDMENTS GOING FORWARD. BECAUSE YOU CANNOT WAIT UNTIL IT HAPPENS TO FIGURE OUT. YOU HAVE TO FIGURE OUT EVERY POSSIBLE WAY A PATIENT CAN GO THROUGH A STUDY, EVERY CASE REPORT FORM THEY'RE GOING TO NEED IN EVERY VISIT AND IT IS A LEVEL OF RIGOR THAT'S REALLY I THINK -- IT'S ANOTHER INVESTMENT AND WE ARE GOING TO HAVE FEWER PROTOCOL AMENDMENTS BECAUSE OF IT. >> I DIDN'T THINK OF THAT. THAT'S ANOTHER METRIC TO LOOK AT. AMENDMENTS DROP OFF OVER TIME. >> HAVE YOU THOUGHT ABOUT THE COORDINATION WITH GENOMIC DATA HOPING THE PUSH A BUTTON AND GET THE CLINICAL PHENOTYPE? >> THERE ARE DATA SETS THAT MIGHT BE AVAILABLE OUT THERE. RIGHT NOW THE STRUGGLE WE HAVE IS BECAUSE WE HAVE TO BANG THAT AGAINST 50 DIFFERENT WAYS OF DOING BUSINESS. NOT SAYING IT'S EASY TO RESOLVE BUT NOW WE HAVE THE FIGURE OUT ONE WAY AND SHOULD HOPEFULLY SIMPLIFY THOSE ISSUES GOING FORWARD. >> SO MORE SPECIFICALLY YOU'RE TALKING TO PEOPLE TO RE-ENGINEER caBIG, ET CETERA? >> THEY ARE ABSOLUTELY THIS IS A TRANSNCI INITIATIVE AND WE MAKE SURE THEY'RE ON THE SAME PAGE AS WE ARE. THEY KNOW WHERE WE ARE. WE'RE LEVERAGING THEIR LICENSE, THERE'S -- AND THEY ARE LEVERAGING THE EXPERIENCE WE HAVE WITH THE COOPERATIVE GROUPS DEPLOYING THE APPLICATION AND WE GET THOSE IDEAS TOGETHER TO MAKE SURE WE DO THIS IN A THOUGHTFUL WAY THAT BENEFIT THE ENTIRE ONCOLOGY COMMUNITY. >> OKAY. THANK YOU VERY MUCH. WE'RE SCHEDULED FOR A LUNCH BREAK UNTIL 1:15. WE'LL PICK UP AT THAT POINT WITH A PRESENTATION FROM DR. HELMAN AND CENTER FOR CANCER RESEARCH.xjjtVX >> LET'S GET STARTED. SO AS WE MENTIONED ONE OF THE THINGS THAT CTAC IS CHARGED WITH IS HELPING NCI WITH THE INTRAMURAL CANCER PROGRAM. WE HAVEN'T SPENT A LOT OF TIME THINKING ABOUT THAT. WE REALLY FOCUSED I THINK MOSTLY ON EXTRAMURAL. ALMOST EXCLUSIVELY ON EXTRAMURAL BUT BUT WE THOUGHT WE SHOULD BROADEN OUR SCOPE AND ASK DR. HELMAN TO GIVE US AN UPDATE ON THE CENTER FOR CANCER RESEARCH CLINICAL TRIALS PORTFOLIO AND WHAT THEY HAVE DONE TO WORK ON SOME OF THE TIME LINE ISSUES THAT THE ODWG HAS PUT FORTH FOR THE EXTRAMURAL COMMUNITY. >> IT'S ONE LITTLE BRIEF ADMINISTRATIVE THING BEFORE YOU START. I WAS ADVISED AT 2 O'CLOCK SOME NATIONAL ALARM IS OCCURRING. (OFF MIC) >> SO IN THE NEXT 45 MINUTE, JIM DIDN'T KNOW ANYTHING ABOUT THE INTRAMURAL PROGRAM SO I'LL TRY TO GIVE HIM A BRIEF BACKGROUND. AND FOCUS ON SOME ISSUES BROUGHT UP THIS MORNING THAT WE HAVE REALLY BEEN TRYING TO WORK ON IN THE INTRAMURAL CLINICAL PROGRAM. SO THIS IS OUR CLINICAL VISION. THAT IS TO IMPROVE THE OUTCOME OF PATIENTS WITH CANCER BUT THESE BULLETS SUMMARIZE HOW WE THINK DO THIS BY ENGAGING RESEARCHERS IN INVESTIGATOR INITIATED CLINICAL RESEARCH IN WHAT WE THINK IS A STRONG TRANSLATIONAL RESEARCH CULTURE BY HAVING THE ABILITY TO HAVE FLEXIBLE FUNDING TA'S AN AREA OF SUPPORT, INNOVATIVE HIGH IMPACT BENCH TO BEDSIDE RESEARCH THROUGH ACCESS TO THE LARGEST PUBLICLY FUNDED RESEARCH CENTER IN THE WORLD AND CLEARLY THINK OF OUR PROGRAM AS COLLABORATIVE WITH RESEARCHERS NOT ONLY THROUGHOUT THE NIH BUT THE EXTRAMURAL. SO OUR PRIORITIES ARE OBVIOUSLY ONE TO TAKE DISCOVERIES MADE WITHIN THE LABORATORY OF THE CCR BUT ALSO EDUCATION AN TRAINING IS A PRIORITY TO DESIGN AND EXECUTE NOVEL SCIENCE BASED CLINICAL TRIALS. THESE SOUND FAMILIAR TO ALL OF YOU. FOCUS ON PRECISION MEDICINE, MOLECULARLY BASED PRECISION MEDICINE. TO CLEARLY INTEGRATE TECHNOLOGY AND CORRELATIVE SCIENCE IN ALL OF OUR CLINICAL STUDY, SOMETHING THAT IS OFTEN DIFFICULT TO DO. ALSO WE HAVE THE ABILITY TO STUDY WHERE CANCERS AREN'T ADEQUATELY STUDIED BECAUSE WE CAN TRAVEL PATIENTS FROM THROUGHOUT THE UNITED STATES. LIKE YOU, WE'RE UNDER PRESSURE FINANCIALLY OVER THE LAST FEW YEARS AND PUT IN PERSPECTIVE, WE HAD TO MAKE AN ACROSS THE BOARD 8% CUT IN THE INTRAMURAL PROGRAM THROUGHOUT OUR LABORATORY AND CLINICAL PROGRAM LAST YEAR SO WE NEED TO LEARN HOW TO DO MORE WITH LESS JUST LIKE YOU DO. WE NEED TO DEVELOP FLEXIBLE TARGETING APPROACHES TO SOLVE COMPLEX PROBLEMS TO EMBRACE NEW INITIATIVES THAT WILL MAKE SURE THAT WE MAKE PROGRESS TO CLEARLY USE THE SCIENCE-BASED KNOWLEDGE THAT WE'RE GENERATING ABOUT THE DISEASE AND PROGRESSION SO THAT WE CAN INTERVENE IN EARLIER STAGES. AND INTEGRATE BIOMEDICAL TECHNOLOGIES IN EVERY CLINICAL TRIAL SO I HAVE HIGHLIGHTED THAT BECAUSE THAT'S SOMETHING WE HAVE BEEN WORKING EXTREMELY HARD TO DO. SO EACH PATIENT IS TREATED FOR TUMOR-SPECIFIC MOLECULAR QUALITIES AS WELL AS HOST OR PATIENT MOLECULAR CHARACTERISTICS. SO WHAT'S DISTINCT ANT THE INTRAMURAL PROGRAM? I DON'T THINK ANYTHING IS TOTALLY DISTINCT BUT I HAVE LISTED UNIQUE ATTRIBUTES. THERE IS AS I MENTIONED BEFORE, SUSTAINED SUPPORT FROM HIGH RISK HIGH IMPACT RESEARCH. THAT MEANS TO ME THAT WE SHOULD FAIL IN SOME THINGS BECAUSE IF WE'RE SUCCESSFUL IN EVERYTHING WE DO WE'RE NOT TAKING THEM UP. WE REALLY DO HAVE A HIGHLY INTERACTIVE CULTURE AND WHEN WE MERGE THE DIVISION OF BASIC SCIENCE WITH THE DIVISION OF CLINICAL SCIENCE, TO CREATE THE SENOR FOR CANCER RESEARCH, IT REALLY CREATED A CULTURE, ONE CULTURE ACROSS OUR LABORATORY RESEARCHERS AND OUR CLINICAL RESEARCHERS. THERE IS AN ACTIVE BENCH TO BEDSIDE AND BEDSIDE TO BENCH CULTURE. WE HAVE ACCESS TO THIS WONDERFUL FACILITY CALLED THE CLINICAL SENOR. WE HAVE A COMMITMENT TO RARE CANCERS AND THE UNDERSERVED POPULATION. WE CAN LAB RATE WITH PARTNERSHIPS ACROSS NIH AND AS WELL AS ACADEMIA. WE HAVE THE FLEXIBILITY IF THERE'S AN EMERGENCY, SO WHEN THE SARS EPIDEMIC HIT FOR EXAMPLE, NIAID PUT A SUBSTANTIAL SOURCE OF THE PORTFOLIO TO FIGURE OUT WHAT SARS WAS. SO WE CAN RAPIDLY REDEPLOY FOR THE FEDERAL GOVERNMENT. SO THE QUESTION WE HAVE BEEN FACED WITH, HOW CAN WE BE MORE EFFICIENT AS COST INCREASES AND BUDGETS GROW TIGHTER? SOME OF YOU MAY HAVE HEARD, THERE'S A REAL CRISIS IN FUNDING THE CLINICAL CENTER, IN ALL NIH. COSTS ARE GOING UP, THERE'S NO MORE MONEY. HOW DO WE PROTECT THIS FACILITY AND MAKE SURE WE'RE DOING THE MOST IMPORTANT CLINICAL VERGE. CLEARLY WE CAN'T DO ANYTHING, WE CAN AFFORD TO DO THINGS THAT MAXIMIZE OUR IMPACT PER DOLLAR SPENT. PETER, THIS WILL PROBABLY SOUND FAMILIAR TO YOU. HOW WE MEASURE CALL. IT'S THE SAME ISSUE YOU GUYS WERE STUDYING. HOW DO WE MEASURE IMPACT. AND HOW STUDIES ARE DONE HERE AS OPPOSED TO WHY WOULDN'T IT BE BETTER AT A CANCER SENOR. NOT SO MUCH IN THE COOPERATIVE GROUPS BECAUSE OUR STUDIES AS YOU'LL SEE IN A MOMENT -- WE NEVER DO THINGS WITH STUDIES, WE DO SMALLER STUDIES BUT OUR CLINICAL PROTOCOLS HAVE TO SUPPORT THE MISSION OF THE CRR TO BE SCIENTIFICALLY EXCITING, MEET PEER REVIEW STANDARDS OF SCIENTIFIC DESIGN AND LAST BUT NOT LEAST, AS WE'VE ALL HEARD FROM REVIEW HAS A HIGH LIKELIHOOD FOR TIMELY PATIENT ACCRUAL. SO BASED ON SOME OF THESE PRELIMINARY DISCUSSIONS, IN THE LAST YEAR WE DEVELOPED STRATEGIC ALIGN M AND RESOURCE PLANNING CHECKLIST THIS WAS A REAL CHANGE IN CULTURE ACROSS OUR CLINICAL BRANCHES. WHEN YOU GIVE US OUR BUDGE WE MANAGE OUR CLINICAL PROGRAM. WE SAID NO BECAUSE A LOT OF THE INFRASTRUCTURE YOU'RE NOT PAYING FOR. AND WE NEED TO LOOK ACROSS ALL THE CLINICAL PROGRAMS AND MAKE SOME PRIORITY DECISIONS. SO EVERY TIME YOU PROPOSE A STUDY NOW, YOU HAVE TO FILL OUT THIS WHAT WE CALL THE SARP. SO IT'S A SIX SECTION FORUM, WHERE THE MAJOR SESSIONS ARE THE STUDY IMPACT AND BY THAT I MEAN WHY IS THIS AN IMPORTANT STUDY TO BE DONE IN THE INTRAMURAL PROGRAM NOW, WHEREAS DEMOGRAPHIC, WHAT KIND OF RESOURCES DO YOU NEED AND ARE ANY OF THESE UNIQUE TO WHAT WE HAVE AVAILABLE HERE. AND OTHER ADDITIONAL PERTINENT INFORMATION. SO THIS IS JUST THE FORM, YOU CAN SEE THE STUDY IMPACT, STUDY DEMOGRAPHICS. RESOURCE NEEDS, AND HOW DOES THIS ALIGN WITH OUR MISSION. BUT INTO FOCUS ON THIS SECTION TOO. YOU HAVE YOU HAVE TO ANSWER ALL THESE QUESTIONS WHEN YOU PUT FORWARD A PROPOSAL. HOW IS THIS CONSEQUENTIAL TO THE FIELD? WILL IT CHANGE RESEARCH PARADIGMS OR PRACTICE OR WILL IT BE A THEFT IN DOING THOSE. WE WISH OUR PARADIGMS, I'M NOT NAIVE TO THINK WE WILL DO IS PARADIGM CHANGING STUDIES BUT ASK OURSELVES THESE QUESTIONS HONESTLY. LEADERS IN THE FIELD CONSIDER THIS HIGH IMPACT. AND IF YES, WHY. AND WE ATTEMPT HOW YOU MEASURE IMPACT AND THEY'RE SIMILAR TO WHAT WAS BROUGHT OUT THROUGH CTAC LAST YEAR. PUBLICATIONS, SIGNIFICANT CHANGE IN PARADIGM, MAYBE IT'S SOMETHING THAT WOULDN'T BE STUDIED ANYWHERE ELSE BUT IT'S YET AN IMPORTANT QUESTION. IS IT INVOLVING A NOVEL APPROACH. AND WHAT IS THE BROADER CONTEXT. AND IF IT'S A FAILURE, WILL IT BE A PRODUCTIVE FAILURE WE TALKED ABOUT THAT IN VARIOUS FORUMS ALREADY. WHY CAN'T THE STUDY BE EASILY CONDUCTED ON THE OUTSIDE? BECAUSE IF IT CAN BE MAYBE WE SHOULDN'T BE DOING IT. WE WANT THE MAKE SURE WHAT WE DO IS COMPLIMENTARY, NOT PETTIVE WITH WHAT CAN BE DONE JUST AS EASILY IF NOT MORE EASILY IN THE CANCER SENORS. SO HIGHLIGHT IN RED, OBVIOUSLY WE PUT A LOT OF STOCK IN SOMETHING THAT'S TRANSLATION FROM OUR LABORATORY RESEARCH. THAT CAN THEN MOVE INTO THE CLAY IN THIS CASE. AND IF YOUR ANSWER TO THAT IS YES, YOU HAVE TO EXPLAIN TO US WHY THAT IS. IF I'S PART OF AN EXISTING PROGRAM HOW IS IT MOVING FORWARD, IF IT'S AN EXTENSION OR BECAUSE IT'S A PROGRAM DOES IT NEED TO BE STUDIED IN THE CLINIC. LAST BUT NOT LEAST, IT'S -- THESE ARE FILLED OUT BY THE REVIEW TEAM. SO THIS IS FILLED OUT BY SCIENTIFIC REVIEWERS, NOT THE PI. AND ULTIMATELY HAS TO BE SIGNED OFF ON BY THE BRANCH CHIEF AND SO -- AND BY MYSELF. SO OBVIOUSLY THE GOAL IS TO AS OPTIMALLY AS POSSIBLE DISTRIBUTE OUR RESOURCES ACROSS OUR PORTFOLIO MUCH AS WETATION ABOUT HOW THE NCI CAN DO THIS, THE TRIALS TO MAXIMIZE HOW WE ACHIEVE OUR MISSION. SO THE FIRST SYMBOL WE SET FORWARD IS THIS WOULD BE TRANSPARENT, THAT WE WOULD FOCUS ON IMPACT AND OUTCOMES. AND IF WE HAD TO NOT DO A STUDY, IT'S NOT, WELL, I HAVE BEEN DOING THESE AND I HAVE THIS MONEY, NO. YOU HAVE TO REALLY DEFEND WHY WE SHOULD BE SPENDING TAXPAYER DOLLARS ON THESE PARTICULAR STUDIES. AND KNOWLEDGE UP FRONT THAT THERE WILL BE GOOD RESEARCH STUDIES THAT WE CAN'T FUND, THAT WILL ALLOW US TO HAVE THE MONEY TO FUND THE MOST IMPACTFUL. BASICALLY TO FOCUS ON CONSEQUENTIAL INNOVATIVE AND HIGH IMPACT CLINICAL STUDIES. SO BEFORE I MOVE TO THE NEXT PART, LET ME JUST TELL YOU, I DID ALSO WANT TO TAKE A MOMENT ABOUT THE DURATION OF HOW LONG IT TAKES US TO DO STUDIES SO WE HAD DATA BUILT TO REVIEW OUR PROGRAMS. WE BEGAN WITH A MEETING OF 208 DAYS FROM SCIENTIFIC REVIEW TO OPENING STUDIES. I SAID TO THE TARGET -- THAT'S A LITTLE AMBITIOUS BUT THE FIRST THING WE HAD TO GENERATE AND WE HAVE NOW IN OUR COMPUTER SYSTEM WE HAVE CODED AND AVAILABLE, AND I CAN LOOK AT THIS EVERY MONTH, HOW LONG SCIENTIFIC REVIEW TAKES, HOW LONG SCIENTIFIC REVIEW SUBMISSION TO THE IRB, HOW LONG IRB REVIEW TAKES, ONCE IRB IS APPROVED HOW LONG DOES IT TAKE FROM THE TIME WE SEND TO IT THE CLINICAL CENTERS TO THE HOSPITAL HAS TO APPROVE IT. HOW LONG IT TAKES TO GET CLINICAL SENOR APPROVAL, LAST BUT NOT LEAST, HOW LONG UNTIL OUR FIRST PATIENT IS ACCRUED. SO ALL OF THIS DATA IS COLLECTED PROSPECTIVELY NOW, ABOUT TEN OR 12 CHARTS, I WON'T GO INTO SHOWING YOU BUT WE'RE NOW DOWN TO 95 DAYS SO WE HAVE CUT THIS SUBSTANTIALLY. LARGE PART BECAUSE WE'RE TRACKING IT AND EVERYONE KNOWS WE'RE TRACKING IT. THE OTHER THING WE HAVE INSTITUTED, THIS WAS AMAZING TO ME. SCIENTIFIC REVIEW SORT OF LIKE WHAT WE DO WITH OUR JOURNAL REVIEW. WE INSTITUTED A TWO STRIKES AND YOU'RE OUT. IF YOU SEND SOMETHING TO REVIEW AND IT'S NOT ACCEPTED, YOU HAVE ONE RESUBMISSION. IF IT'S NOT ACCEPTED AFTER SECOND RESUBMISSION IT'S DONE. AND THAT'S BECAUSE ZERO PROTOCOLS COME BACK FOR TWO AND A HALF YEARS. WE ALL KNOW IF WE LIKE A STUDY USUALLY THE CONSENSUS WE SHOULD DO IT HERE. IF WE DONE LIKE IT INSTEAD OF SAYING NO WE DON'T WANT TO DO IT WE NITPICK OR NICKEL AND DIME AND SAY NO BUT INVESTIGATORS WILL KEEP SENDING IT BACK SO NOW WE HAVE TWO STRIKES AND YOU'RE OUT AND THAT SAVED US ENORMOUS AMOUNT OF TIME. SO I WANT TO SPEND A MINUTE TALKING ABOUT SOME OF THE UNIQUE THINGS THAT WE HAVE AVAILABLE IN OUR CLINICAL RESEARCH CENTER. AND I'M GOING TO HIGHLIGHT OUR MOLECULAR IMAGING CLINIC, NOT SO MUCH MENTION BUT WE HAVE NOW PUT IN PLACE THE STANDARD DICED BIOSPECIMEN COLLECTION HOUSED WITHIN THE LABORATORY OF H PATHOLOGY. I'M TALK A LITTLE BIT ABOUT OUR GENOME WIDE PROFILING CORE THAT WE HAVE PUT IN PLACE. I'M NOT GOING TO TALK SO MUCH ABOUT OTHER THINGS AT THIS POINT IN TIME. IMAGING IS A BIG PRIORITY, IT WAS MENTIONED EARLIER HOW IMPORTANT IMAGES IS, WE BELIEVE IMAGING IN MANY WAYS IS -- HAS TO SOLVE IN SOME WAY SOME OF OUR PROBLEMS BIOMARKERS, WE BELIEVE WE SHOULD BE DOING MORE FUNCTIONAL IMAGING. ULTIMATELY PERHAPS BEING ABLE TO BLUR THE LINE BETWEEN I IMAGINING AND -- IMAGING AND START ARGUING ABOUT TURF. SO WE HAVE BASIC DISCOVERY RESEARCH. WE HAVE TRANSLATIONAL APPLICATION, WE'RE WORKING TO BRING THIS TO THE CLINIC. WE BELIEVE THAT WE SHOULD BE ABLE TO USE THIS TO ENHANCE HERB DETECTION, DIAGNOSIS AND TO MONITOR TREATMENT. SO WE HAVE A PRE-CLINICAL TESTING PROGRAM AND VALIDATION, AND WE TRY TO PUT IMAGING INTO EVERY ONE OF OUR CLINICAL TRIALS MOVING TOARD FORWARD. IT'S OUR ULTIMATE HOPE, RATHER THAN WAITING FOR 10 TO THE 12th OR OVER A BILLION CELLS TO SEE SOMETHING, TO MEASURE IT, IF WE CAN FIND RECURRENCE BEFORE WE SEE MEASURABLE TUMOR VOLUME PERHAPS WE CAN INTERVENE IN A MORE APPROPRIATE POINT ALONG THE PATIENT'S NATURAL HISTORY BEFORE RECURRENCE AN MAYBE THEN OUR THERAPIES WILL BE MORE EFFECTIVE. BECAUSE AS WE ALL KNOW WITH RARE EXCEPTIONS AFTER PATIENT RECURS WE DONE HAVE MANY OPTIONS TO CURE. SO WE SET UP UNDER THE DIRECTION OF PETE (INDISCERNIBLE) WHO USED TO BE IN THE DEPARTMENT OF RADIOLOGY HERE, AT AN IMAGING CLINIC. SO WE HAVE A CT MR, WE HAVE A THREET MAGNET. THESE ARE THE PROTOCOLS THAT WE HAVE. THIS IS NOW AN IMAGING CLINIC THAT OUR PATIENTS CAN HAVE AVAILABLE TO ANY PATIENT ON THE CLINICAL PROTOCOL. TOTALLY INDEPENDENT OF THE HOSPITAL. SO IF WE NEED TO IMAGE A PATIENT 45 MINUTES THREE DAYS IN A ROLE WE CAN DO THAT SO THESE ARE ONGOING STUDIES THAT ARE AVAILABLE AND I DON'T NEED TO GO THROUGH THE LIST. BUT IT'S AN EVER INCREASING AMOUNT OF IMAGING REAGENTS THAT WE HAVE AVAILABLE TO US. AND VERY MUCH TRYING TO TIE EACH TO CLINICAL STUDIES. NOW WE ASK WHEN A CLINICAL INVESTIGATOR IS DEVELOPING A TRIAL TO SIT DOWN WITH (INDISCERNIBLE) AND ASK IF THERE'S AN IMAGING MODALITY THAT MIGHT TEACH US MORE THAN WE HAD THOUGHT ABOUT OURSELVES. WE ALSO IN COLLABORATION WITH THE CLINICAL CENTER HAVE AN NIH SENOR FOR INTERVENTIONAL ONCOLOGY HEADED BY BRAD WOOD. HE IS VERY INTERESTED IN USING INTERVENTIONAL RADIOLOGY AS ANOTHER MODALITY SO HE WORKS CLOSELY WITH PETE CHOIKE. SO TALK A MOMENT ABOUT MOLECULAR PROFILING CORE. THIS WAS SOMETHING WE ALSO ASKED, THIS WAS NOW SET UP BY PAUL MELSER, AGAIN WE ASK ALL OUR CLINICAL PROTOCOLS TO THINK ABOUT THE USE OF THIS CORE IN THE DEVELOPMENT OF THEIR RESEARCH QUESTION, SO IT GOES THROUGH A TISSUE PROCUREMENT AND PROCESSING FACILITY WHERE THERE'S ANNOTATION BUT WE ALSO HAVE ACCESS OF COURSE TO LASER CAPTURE MICRODISSECTION AND THEN THE CORE ITSELF HAS THE CAPACITY FOR PROFILING SEQUENCING EXPERIMENTAL IMAGING, PHARMACOGENOMICS. SO WE HAVE THE FACILITY IN MACE, THE DIRECTOR IS PAUL MELTSER AROUND MANY IS CLIA CERTIFIED. DIRECTS KEITH KILLIAN TRAINED IN PATHOLOGY AND HE'S NOW CENTER IN RUNNING THIS CORE. SO WE ARE USING THIS FOR BOTH TUMOR CLASSIFICATION AS WELL AS IN DISCOVERY AND CLINICAL TESTING UNDER KLIA. THE PROFILING CORE OPERATES ON A COLLABORATIVE MODEL PROVIDING A FULLY INTEGRATED TEAM THAT WORKS WITH OUR CLINICAL INVESTIGATORS AND YOU CAN SEE HERE THESE ARE THE CURRENT ASSAYS THAT ARE AVAILABLE FOR CLINICAL STUDIES, MICROARRAYS, METHYLATION, DNA SEQUENCING THOUGH WE STILL, NO ONE HAS CLIA CERTIFICATION TO NEXT GENERATION SEQUENCING. WE HAVE TO THEN GO BACK AND DO SAENGER SEQUENCING. BUT WE'RE WORKING ON MOVING THESE THINGS IN TO WHAT I CALL CLINICAL TIME BECAUSE RIGHT NOW SOME OF THE SEQUENCING THINGS STILL TAKE MORE TIME THAN YOU HAVE IF YOU HAVE -- WANT TO MAKE A DIAGNOSIS AND AN INTERVENTION.0 I INNOCENCE CONCERT WITH OUR CLINICAL CORE WE DO HAVE A SEQUENCING FACILITY WORKING HARD TO BRING SOME OF THESE TONE OUR PROFILING CORE. I LIST HERE WE'RE USING THE ALUMINA PLATFORMS, WE NOW HAVE INSTALLED A BACK BIOSEQUENCER, THE ADVANTAGE OF THAT IS MUCH QUICKER DATA GENERATION. IT'S NOT OPERATIONAL YET BUT WE'RE OPTIMISTIC TO BRING AS MUCH AS WE CAN INTO MAKING REAL CLINICAL DECISION. THERE'S A BIG RESEARCH COMPONENT, IT'S BEEN A ACTIVE COURSE, IT'S BEEN QUITE PRODUCTIVE. SO OBVIOUSLY THE IMPACT OF ALL OF THIS STO ENSURE THAT WE GET THE GREATEST AMOUNT OF INFORMATION FROM EVERY PATIENT PARTICIPATING IN A CLINICAL TRIAL. AND GAIN DETAILED INFORMATION THAT COULD LEAD TO QUESTIONS, THAT COULD RAPIDLY ACCELERATE THE PACE OF TRANSLATION OF THIS EXPLOATDING TECHNOLOGY AND CLINICAL APPLICATION. SURE EVERY ONE OF YOU AT YOUR CANCER CENTERS ARE HAVING THESE SAME DISCUSSIONS. THE DIFFERENCE IS WE CAN PICK AND CHOOSE, WHAT DISEASES WE STUDY AND FOCUS AND MAKE SURE WE CAN OPERATIONALIZE IN A FEW DISEASES HOW THIS WILL ACTUALLY LOOK MOVING FORWARD. SO ONE OF THE AREAS THAT BECAME APARENT AS WE WERE GOING THROUGH THESE DISCUSSIONS IS WELL, WE ALL KNOW WE WANT IMPACTFUL SCIENCE BUT HOW MIGHT WE ACTUALLY INVOLVE THE COMMUNITY, BASIC SCIENTISTS AND OUR CLINICAL SCIENTISTS, AND THIS DISCUSSION WAS GOING ON AT THE TIME THESE PROVOCATIVE QUESTIONS WOULD BE POSTED, AND WE'LL HEAR FROM ED HARLOW IN LITTLE BIT. SO WE CAME ONE THE IDEA, WE SHOULD TALK ABOUT WITHIN THE INTRAMURAL PROGRAM MAJOR OPPORTUNITIES. WHERE DO WE THINK WE HAVE MAJOR OPPORTUNITIES TO REALLY ADVANCE THE FIELD? NOT THAT EVERYTHING WE DO IS A MAJOR OPPORTUNITY BUT IF WE HAD TO PICK THREE OR FOUR, HOW MIGHT WE THINK ABOUT THAT? SO WE SPENT TIME, WE HAD A STEERING COMMITTEE AND WE DECIDED THAT A MAJOR OPPORTUNITY SHOULD ADDRESS THE FUNDAMENTAL PROBLEM IN ONCOLOGY BROAD APPLICATIONS ACROSS MULTIPLE CLINICAL AND LABORATORY BRANCHES WHERE CCR HAS RARE CAPABILITIES OR DIRECT POPULATIONS. AND IT SHOULD FOCUS OVER THE NEXT 3 TO 5 YEARS THE ACHIEVE SPECIFIED GOALS AND DELIVERABLES, THAT IF ACHIEVED WOULD BE CONSIDERED A SIGNIFICANT STEP FORWARD BY THE ENTIRE CANCER COMMUNITY AND IT HAD TO HAVE AT THE END OF IT A CLINICAL STUDY. SO IT COULDN'T BE A LABORATORY MAJOR OPPORTUNITY. THIS HAD TO BE SOMETHING THAT COULD BE TESTED IN PATIENTS. SO I HAD -- WE HAD A LOT OF DISCUSSION BUT I WANT PEOPLE TO UNDERSTAND BY DEFINITION THIS WAS NOT A PERMANENT ORGANIZATIONAL UNIT. BUT A FOCUSED GROUP THAT CAME TOGETHER TO ACTUALLY CARRY THIS OUT IN THE 3 TO 5 YEAR TIME FRAME. SO IT WAS A MAJOR THEME, PARADIGM SHIFTING, THE RATIONALE FOR WHY IT'S DONE HERE AND COLLABORATE ACROSS MULTIPLE BRANCHES, IF IT WAS JUST ONE BRANCH THAT'S THE BRANCH ACTIVITY, THAT'S IN THE A MAJOR OPPORTUNITY. SO WE HAD OTHER GOALS OF COURSE THAT WOULD INCREASE COMMUNICATION BETWEEN BASIC AND CLINICAL SCIENCES. IT WAS AMAZING TO FINE OUT THAT SOME OF OUR BASIC SCIENCES HAD IDEAS THAT THOUGHT SHOULD BE TESTED IN CLINIC BUT DIDN'T APPROACH OUR CLINICAL SCIENTISTS. AND TO UNDERSTAND THE IMPORTANCE OF THESE, SO THIS IS TALKING ABOUT WE HAD A RETREAT ABOUT TWO WEEKS AGO, SO AFTER WE PUT THESE TOGETHER, WE BROUGHT TOGETHER THE COMMUNITY TO DISCUSS THESE. THAT'S ANOTHER GOAL IS TO PROVIDE TRANSPARENCY SO EVERYONE KNEW WHAT WE WERE THINKING ABOUT. FIRST WE HAD TO FIGURE OUT WHAT WOULD A MAJOR OPPORTUNITY LOOK LIKE? I CAN TELL YOU WHEN WE DECIDED TO GO FORWARD IT TOOK US TWO AND A HALF MONTHS TO WRITE DOWN ONE MAJOR OPPORTUNITY. IT'S NOT SO TRIVIAL. SO WE HAD TO PUT A LAY SUMMARY, WE HAD TO EXPLAIN ITS UNIQUENESS, THE OVER ARCHING STRATEGY, THE ANTICIPATED TIME LINE, THE TARGETED POPULATION, THE THERAPEUTICALS, ET CETERA. SO WE WORKED ON THESE, AND WE INVOLVED THE ENTIRE CCR COMMUNITY, WE HAD A WEB SIETD. PEOPLE WERE ALLOWED TO PUT ON THEIR OWN SO WE DEVELOPE w FEW EXAMPLES, THEN WE OPENED IT UP AND VETTED 26 MAJOR OPPORTUNITIESCH THESE WERE THE 8 MAJOR OPPORTUNITIES THAT WERE ACTUALLY CONSIDERING AND DISCUSSED AT THE RETREAT TWO WEEKS AGO. AND THEY'RE LISTED HERE, ONE TO TARGET INFLAMMATION IN CANCER. ONE WAS TO DEVELOP A MATRIX DRUG SCREENING FOR COME BY THAITION THERAPIES UTILIZING THE ABILITY TO SCREEN ONE DRUG AND LOOK FORESI NER JIS ACROSS MULTIPLE CELL LINE -- FOR, SYNERGIES ACROSS MULTIPLE CELL LINES. MUTATIONS INDEPENDENT OF HISTOLOGY, MONITORING THE EPIGENOME IN CANCER, COMBINE PROGRAM LOOKING AT IMMUNOTHERAPY AND PHARMACO THERAPY. ATTACKING CANCER BASED ON ITS METABOLIC BASIS. THERE IS ONE LOOKING AT RARE CANCERS AND GENETIC PRE-DISPOSITION SYNDROMES AND ONE THAT PROPOSED CHARACTERIZING TRANSITION FROM PRE-MALIGNANT OR SMOLDERING CANCERS TO MALIGNANT TUMORS. SO THE RETREAT THEN HAD A STRUCTURED DISCUSSION SO WE HAD TO DISCUSS WHAT ARE THE PERCEPTIONS FROM THE EXTERNAL AND INTERNAL ONCOLOGY COMMUNITIES. SUCH THAT IN FIVE YEARS HOW WOULD THIS CHANGE THE FACE OF CANCER. WHY SHOULD WE DO THIS HERE, WHAT ARE UNIQUE ATTRIBUTES THAT WE HAVE. IT'S INTERESTING, SOME OF THESE CAME OUT WELL, YOU KNOW WHAT, THIS IS BEING DONE ELSEWHERE, WE SHOULDN'T DO IT HERE. HOW CAN WE APPROVE THOSE AND HOW DO WE INTEGRATE CURRENT RESEARCH IN DIRECTION OF MAJOR OPPORTUNITY. THAT IS WILL THE COMMUNITY WANT TO PARTICIPATE IN THAT SO WE SPENT A WHOLE DAY, WE HAD 100 PEOPLE PARTICIPATING AND THEN WITH WE ASKED PEOPLE TO VOTE. AND THERE WERE 90% RESPONSE RATE AFTER THE RETREAT. THEY HAD A WEEK TO RESPOND. 0 WERE AFTER RETREAT AND THERE WERE 18 THAT WERE ENGAGED IN THE PROCESS SO THEY RESPONDED. YOU CAN SEE OF THE PEOPLE WHO RESPONDED 31 IDENTIFIED THEMSELVES AS BASIC SCIENTIST, 49 AS TRANSLATIONAL OR BASIC AND CLINICAL, AND 19 AS PURELY CLINICAL. SO FEEDBACK, TYPES OF RESPONSES WE GOT IS THAT IT WAS A GOOD EXERCISE, PEOPLE REALLY SEEMED TO APPRECIATE THE INTERACTION AND ABILITY TO COME UP WITH SOME MEASURES OF SUCCESS. ONE PERSON RANKED THE OPPORTUNITY ON HOW THEY CONVERGE MANY CANCER DISCIPLINES. ANOTHER ONE SAID IT WAS A HARD DECISION. WE ASKED THEM TO RANK TOP 3. SO I WON'T GUF YOU DETAILS OF THE RESULTS BECAUSE WE'RE STILL NOW DISCUSSING THIS BUT THE INTERESTING THING I WANT TO SHOW, THESE WERE CLINICAL BRANCHES ARC THROUGH J AND YOU CAN SEE HERE ARE THE MAJOR OPPORTUNITIES. YOU CAN SEE EVERY BRANCH LIKE A LOT OF OPPORTUNITIES, SO IT WASN'T ONE BRANCH PUSHING ONE MAJOR OPPORTUNITY SO EVERY ONE OF THE OPPORTUNITIES CUT ACROSS ALMOST EVERY ONE OF OUR CLINICAL BRANCHES WHICH IS WHAT WE INTENDED TO DO. SO OUR NEXT STEP AND NANCY WILL PARTICIPATE IN THIS NEXT WEEK AS A MEMBER OF BRC, WE HAVE A BSC WORKING GROUP ADVISING ME ON OUR IMPLEMENTATION BECOMING MORE -- GETTING OUR TRIALS OPEN IN A MORE EFFICIENT MANNER. BUT THEY'RE NOW INVOLVED IN OUR MAJOR OPPORTUNITIES. SO WHEY I'M GOING TO PRESENT THESE MAJOR OPPORTUNITIES IN AN UNBIASED FASHION AND THEY'RE GOING TO VOTE. SO WE'RE GOING TO INCORPORATE ALL THE FEEDBACK FROM BOTH OUR BOARD OF SCIENTIFIC COUNSELORS MADE UP OF EXTRAMURAL ADVISERS, AND THE VOTES THAT WE GOT FROM THE INTRAMURAL GROUPS THAT PARTICIPATED IN THE RETREAT. THEN BOB WILTROUT, WILL COLLATE THIS INFORMATION AND COME UP WITH A A PRIORITY LIST WE WILL DISCUSS WITH HAROLD VARMUS AND JIM, THE DEPUTY, ONCE WE HAVE AGREEMENT THESE ARE MAJOR OPPORTUNITIES WE CAN DO AND CONTACT LEADERS WHO PUT IN THAT EFFORT AND ASK THEM TO COME UP WITH A MUCH MORE SPECIFIC DETAILED SCHEDULE AND RESOURCE LIST AND OUR HOPE IS BY JANUARY WE'LL BE ROLLING OUT. WE DON'T KNOW. BECAUSE PART WILL DEPEND ON THE BUDGET. WHETHER 2, 1, 4, I DON'T THINK WE'LL HAVE MORE THAN FOUR BECAUSE WE HAVE TO PUT RESOURCES INTO THESE MAJOR OPPORTUNITIES WHICH MEANS WE HAVE TO TAKE RESOURCES OUT SOME OF OUR OTHER CLINICAL ACTIVITIES. SO I WANT TO END WITH A QUICK SNAP SHOT WHERE WE ARE AND WHERE WE HOPE TO GO TO TRY TO GIVE YOU A MORE GRAPHIC VISUALIZATION. SO WE ARE AT THE NCI INTRAMURAL 14% OF THE OVERALL INTRAMURAL NIH PROGRAM AND YET WE'RE ALMOST 40% OF THE CLINICAL PROGRAM. WHEREAS LAST YEAR WE WERE 30% INPATIENT DAY, 37% OF NEW PATIENT VISITS TO THE CLINICAL SENOR SO WE ARE A MAJOR CHUNK OF THE USE OF THE CLINICAL SENOR. SO WHEN I LOOK, HERE ARE THE CLINICAL BRANCHES AND THE NAMES ARE NOT RELEVANT. YOU CAN SEE THAT WE HAD ABOUT 50% OF OVERALL PROTOCOLS IN ONCOLOGY PEDIATRIC ONTOLOGY AND SURGERY AND THEN WE HAD A SMATTERS OF OTHER PROTOCOLS ACROSS SOME OF THESE OTHER BRANCHES. IF YOU LOOK AT DISEASE SIETSZ, MOST OF THEM WERE -- THERE'S A LARGE NUMBER OF LYMPHATIC AND HEME LOGIC TUMOR, MOST WERE MULTIPLE CANCER TYPES BECAUSE WE TEND TO DO PHASE 1 STUDIES AND YOU CAN SEE THE OTHER AREAS WHERE WE HAVE MULTIPLE CLINICAL STUDIES. ANOTHER WAY ABOUT THIRD OUR TRIALS ARE PHASE 1 AND 50% ARE PHASE 2. SO REALLY 85% ARE PHASE 1 OR PHASE 2, IT'S 95% OF WHAT WE DO EARLY PHASE. WE WILL ONLY PARTICIPATE IN PHASE 3 STUDIES, IF WE'RE LUCKY AND ONE OF THESE STUDIES IS POSITIVE ENOUGH THAT IT'S TAKEN UP BY THE CLINICAL -- BY THE GROUPS, IT WAS GENERATED HERE, WE MAY HAVE A PI THAT WANTS TO PARTICIPATE IN THAT. THAT WILL BE THE WAY WE PARTICIPATE IN A PHASE 3 TRIAL. SO WE'RE PHASE 1 CLASSIC PHASE 1, EARLY PHASE 2. BUT I WANT TO GIVE YOU AN ILLUSTRATION OF SOMETHING THAT'S A DIFFERENT WAY OF LOOKING AT THE CLINICAL CENTER. ABOUT TWO YEARS AGO NOW WE STARTED THIS PEDIATRIC WILD TYPE. THE REASON WE DID THAT IS WE SEE ONE OR TWO PATIENTS A YEAR, COLLEAGUES AROUND THE COUNTRY SEE ONE PATIENT A YEAR AND IT BECAME CLEAR THAT NOBODY KNEW WHAT TO DO WITH THESE PATIENT, NONE HAD PDGFR MUTATION. ALMOST NONE RESPONDED TO STANDARD TYROSINE KINASE INHIBITORS. SO WE SIMPLY DIDN'T KNOW WHAT TO DO WITH THESE PATIENTS. SO WE BROUGHT IN A CONSORTIUM, I GOT FUNDING FROM THE OFFICE OF RARE DISEASES. AND WE BROUGHT IN DOCTORS FROM AROUND THE COUNTRY, PARTICULARLY SOW ZAHN GEORGE, GEORGE DEMETRIUS, DANA-FARBER AND JONATHAN TRENT AT MD ANDERSON AND WE HAVE SEEN 75 PATIENTS WITH WHAT WE CALL PEDIATRIC WILD TYPE. IT TURNS OUT THAT IT BECAME VERY CLEAR TO US THAT THESE PATIENTS ALMOST UNIFORMLY HAD LOST OF FDH SO THEY WERE ALL DEFINED BY NO MUTATION. BUT WHEN THEY WERE REALLY THE YOUNG PATIENTS, PATIENTS WHO HAD ONCE SAID WE DON'T KNOW WHOA THE DISEASE CUT OFF IS, WE CALL THEM FDH MUTANT. SO 100% TURNED OUT AND INTERESTINGLY ENOUGH, ABOUT A THIRD ACTUALLY HAD GERM LINE MUTATIONS. SO THAT PAPER WAS PUBLISHED IN PNAS BUT MORE STRIKINGLY WE BEGAN TO LOOK AT THE BIOLOGY OF THESE TUMORS. SO IN THIS I'M SHOWING YOU, THIS IS FDH IMMUNOHISTOCHEMISTRY, SO THIS WAS A STANDARD PATIENT WHO HAD NON-PDGFR WILD TYPE IN ADULT PATIENT AND TURNS OUT LIKE ALL OF OF THEM WERE EXPRESSED PLENTY OF FBH AND IF WE LOOK AT THEIR -- IF WE DID A CGH THEY HAD MULTIPLE GENETIC AB B NORMALITIES LIKE WE SEE WITH MOST CANCERSCH THIS IS A TYPICAL FDH NEGATIVE WHICH WE THINK IS MORE PEDIATRIC NORM. YOU CAN SEE THE ONLY FDH STAINING IS IN THE NORMAL TISSUE HERE, NOT IN THE TUMOR CELLS. AND IF YOU LOOK AT TUMORS THEY ARE COMPLETELY SILENT GENETICALLY. SO THAT WAS PRETTY STRIKING. NOW, WITH KEITH KILLION AND PAUL MELSER WE DID A GLOBAL GOLDEN GATE ANALYSIS, THESE TUMORS LOOK LICK THIS AND THESE HAD A DIVERGENT METHYLATION PATTERN. SO COMPLETELY DIFFERENT. MOST CANCERS LOOK LIKE THIS. YOU MAY ZYSEE AREAS OF HYPERMETHYLATIONCH THESE ARE ACROSS THE ENTIRE GENOME HYPERMETHYLATE. SO THEY HAVE A SILENT GENOME AND UNBELIEVABLY HYPERMETHYLATED GENOME. SO THE EPIGENETICS IS -- WE GOT INTERESTED BECAUSE (INDISCERNIBLE) ACROSS THE HAUL FROM ME -- HALL FROM ME HAD BEEN IDENTIFYING FUME RATE MUTATIONS IN KIDNEY CANCER AND WE KNOW WHAT THESE DO IS INHIBIT THE ABILITY OF PROLIEN HYDROXYLACE TO DEGRADE, AND THAT'S WHY THE TUMORS ARE HIF DRIVEN. SO WE WEREN'T TOTALLY SURPRISED THAT WE SAW FDH MUTATIONS BECAUSE THEY'RE IN CYTOMAS AND PARAGANG GLIOMAS SO THIS IS A SYNDROME WHERE THERE'S AN ASSOCIATION WITH GIST WITH THESE PAIR OF GAN GANGLIOMAS. AND ALSO SEEN -- SO I WANT THE TAKE A MOMENT TO SHOW YOU WHAT PRO LIEN HYDROXYLACE DOES AND HOW SUCCINATE BUILDUP INHIBITS THAT ENZYME. SO NORMALLY IT TAKES ALPHA GLUTERATE IN OXYGEN, THE PRO LIEN HYDROXYLACE ENZYME. AND IT THEN DEGRADES HIF AND IT GENERATES SUCKNATE CO-2. -- SXNATE. SO MORE -- SUCCINATE. SO NOR COMES IN AND IT WILL DEGRADE MORE HIF. IN A TUMOR WHERE YOU HAVE EXCESS SUCCINATE WHAT HAPPENS STOIC METRICALLY YOU CAN'T BIND ALPHA CE TA GLUTERATE SO YOU INHIBIT THE ABILITY TO DEGRADE HIF, THAT'S WHY TUMORS ACCUMULATE AND WHY THE SUCCINATE DEHYDROGENASE KIDNEY CANCERS ARE SENSITIVE TO INHIBITION OF HIF. SO EVENTUALLY YOU'LL DO SOME DEGRADATION. IN THESE TUMORS WHERE THERE'S FUME RATE, SIMILARLY FUME RATE BINDS AND INHIBITS THE ABILITY OF ALPHA KEY TA GLUTERATE TO BIND THE PROTEIN HYDROXYLACE TO HYDROXYLATE AND DEGRADE HIF. SO IT TURNS OUT THIS ENZYME WHICH IS ALSO HYDROXYLACE WHAT IT DOES IS IT GENERATES RECOGNIZES METHYLCYTE SCENE IN A HYDROXYLACE, IT ALLOWS THE DEMETHYLATION OF THE GENOME. SO INTERESTINGLY ENOUGH IT'S SIMILAR TO PROLIEN HYDROXYLACE TO FIND METHYL SOORKSITOTENE AND GENERATE THIS IS FIVE HYDROXY METHYL SITOZENE AND SUCCINATE AND CO-2. SO IF YOU HAVE WAY TOO MUCH SUCCINATE LIKE WE THINK WE HAVE IN THIS SXNATE DEHYDROXYNATE MUTANT TUMORS YOU CAN'T DEMETHYLATE YOUR DNA. AND THIS WOULD EXPLAIN WHY WE DONE SEE GENETIC MUTATIONS, BUT WE SEE AN UNBELIEVABLY HYPERMETHYLATED DNA. SO JUST WITH STUDYING A RARE TUMOR WITHIN A YEAR AND A HALF, WE DISCOVERED A METABOLIC PATHWAY IN RARE TUMORS TAKING ADVANTAGE OF THE HATS FIELD RESEARCH RESOURCE SENOR TO BRING RARE PATIENTS. WE IDENTIFIED A NOVEL MECHANISM, GLOBAL HYPERMETHYLATION AND A POTENTIAL TREATMENT, I DON'T HAVE TIME TO GO INTO THIS AS WELL AS ANTI-ANGIOGENIC APPROACHES, MORE FOR KIDNEYS. AND WE WERE ABLE TO USE GENOMICS AND IMAGING. TO DEVELOP NEW APPROACHES TO MONITOR THERAPY. I THINK THIS IS LIKELY TO AFFORD SUB SETS OF OTHER COMMON DISEASES. AND I'LL JUST END WITH IMAGING BECAUSE I THINK THIS WILL BE A NICE SUMMARY TO THIS, SO WE ALREADY HAVE IN OUR IMAGING CLINIC IN OUR PRE-CLINICAL IMAGING CLINIC THE ABILITY TO USE MRI TO MEASURE HYPERPOLARIZED PYRUVATE. AND ALLOW US TO HE SURE THIS PATHWAY SO YOU GET A TRACING THAT SHOWS PYRUVATE, ALANINE AND LACTATE AND ME HUR DIFFERENCES IN TUMORS. SO ACTUAL ONE OF OUR INTRAMURAL INVESTIGATORS IS INVOLVED IN DEVELOPING THIS WITH GE, DEVELOPING THIS ABLE TO DEVELOP THIS HYPERPOLARIZED IMAGING. THEY HAVE BUILT A CLINICAL HYPERPOLARIZER THAT CAN MEASURE PYRUVATE, IT'S USED AT UCSF IN PROSTATE CANCER. SO HERE IS A NORMAL PROSTATE. YOU SEE PYRUVATE. THIS IS TAKEN FROM THIS AREA HERE, YOU CAN SEE ON THE MR. HERE IS THE AREA WHERE THERE'S A LESION AND YOU CAN SEE HOW THE APPEARANCE OF LACTATE, YOU CAN MEASURE LOSS OF LACTATE IN REAL TIME SO WE'RE ABOUT TO GET THIS TO ADD INTO OUR MOLECULAR IMAGING CLINIC. AND IT'S A REASON WE'RE EXCITED ABOUT TRACING METABOLIC DERANGE MS IN CANCER, HERE IS ONE MAJOR OPPORTUNITY IN THE INTRAMURAL PROGRAM. SO IT'S NOT CHEAP, BUT SINCE WE DEVELOPED THIS WE'RE ANXIOUS TO PUT ONE OF THESE HERE AND IT FITS ON TOP OF OUR THREE TESLA MAGNET IN OUR IMAGING PLANT. NOT ONLY CAN WE MEASURE PYRUVATE BUT OIR METABOLITES WITHIN THE PATHWAY. SO I'LL STOP THERE AND BE HAPPY TO ANSWER ANY QUESTIONS OR ANYTHING YOU WANT TO ASK ME THAT I DIDN'T COVER IN THIS SHORT PRESENTATION. >> THANKS VERY MUCH. IN TERMS OF MAJOR OPPORTUNITIES, WHEN DO YOU THINK YOU'LL BE READY FOR LAUNCH? >> JANUARY. >> JANUARY. THAT'S OUR HOPE FOR LAUNCH DAY. >> TWO OR THREE? >> IT DEPENDS, JIM. WE'RE HOPING TO HAVE A COUPLE. IT IS POSSIBLE, WE HAVE A LOT OF DISCUSSION, IF SOME OF OUR GROUPS SAY YOU KNOW WHAT, ALL WE REALLY NEED IS A PIECE OF EQUIPMENT BECAUSE WHAT HAPPENED IS WE HAVE FOUR OR FIVE BRANCHES AND THREE LABS COMING TOGETHER. SO THEY MAY SAY I HAVE SOME OF THIS GOING, I DON'T NEED THAT MUCH. WE HAVE TO BE HONEST BECAUSE THEY REALIZE WHATEVER MONEY WE PUT IN HERE, IT'S COMING OUT FROM SOMEWHERE ELSE WITHIN OUR CLINICAL PROGRAM SO ULTIMATELY IT DO DEPEND ON WHAT THE ACTUAL EXPENSES ARE TO ROLL THESE OUT, ASSUMING THEY GET A HIGH PRIORITY. I'M GUESSING (INAUDIBLE) HIGH PRIORITY. SO LEE, ON YOUR SLIDE WITH THE OPPORTUNITIES TO DISCUSS AT THE RETREAT, THE LAST ONE WAS A PROVOCATIVE ONE TO AMERICAS THE INTERVENTION THERAPY INTERVENTIONS. CAN YOU DESCRIBE WHAT YOU WERE THINKING AND WHAT THE DISCUSSION WAS? >> THIS IS A REALLY INTERESTING DISCUSSION, SCOTT. WE -- IT BASICALLY STARTED WITH PROSTATE CANCER FOLKS AND THE MYELOMA FOLKS SAYING THERE'S A LONG PRE-MALIGNANT STATE. SO HOW -- AND OF COURSE THE BEST PARADIGM IS MYELOMA, WE KNOW MDOT OCCURS WAY MORE FREQUENTLY THAN FRANK MALIGNANCY, IF WE CAN INTERVENE IN THOSE PATIENTS, PROBLEM IS ALWAYS 5% GOES ON TO DEVELOP. SO THE QUESTION IS, CAN WE IDENTIFY THEM WHEN THEY'RE STILL IN AN M DOSE AND IF WE COULD, WOULD IT MATTER? SO THIS LED TO A WHOLE INTERESTING DISCUSSION ABOUT DOES ANYONE THINK WHETHER PROSTATE OR LUNG OR BREAST CANCER OR MYELOMA, WHEN WILL BE SOME COMMON UNDERLYING MECHANISMS, ED JUST WALKED IN, I ASKED ED HARLOE WHAT HE THOUGHT -- THINKS ABOUT THESE. THERE WILL BE SOME COMMON UNDERLYING THEME THAT MAY HELP US, IN OTHER WORDS, WHERE IS THE SWITCH EARLY ON SOME METABOLIC SWITCH COMMON ACROSS BREAST CANCER AN COLON CANCER. THAT WILL BE NEAT BECAUSE THEN WE CAN CHANGE HOW WE MONITOR. SO I DON'T KNOW WHERE THIS IS GOING TO LEAD TO. THERE'S BEEN INTEREST IN INCORPORATING EPIGENOMICS, MAYBE THERE'S AN EPIGENOMIC SIGNATURE THAT CHANGES SO THEY'RE TRYING TO FLESH THIS OUT BUT THAT IS HOW THE DISCUSSION WENT. THAT MAYBE THERE'S SOME COMMON MECHANISMS AND IF WE PICK A FEW MODELS TO STUDY AND BE ABLE TO VET THEM AND OTHER TUMORS TO SEE IF WE CAN COME UP WITH COMMON THEMES TO ALLOW US TO THINK MORE SCIENTIFICALLY ABOUT MONITORING INTERVENTIONS. >> I GUESS (INDISCERNIBLE) I GUESS IN THE SERIES OF TRIALS I COULDN'T TELL FROM THE DIVISION BUT ARE YOU DOING EARLY PHASE TRIALS IN COLLABORATION WITH DCP SOMEHOW INFERENCE IN MULTI-MYELOMA OR EARLY -- IT'S A HUGE OPPORTUNITY TO DO EARLY PHASE DRUG DEVELOPMENT, HIGH RISK, HIGH GAIN OPPORTUNITY. >> THAT'S A GOOD POINT. WE'RE TRYING TO DO MORE. OLA LANGREN WHO CAME FROM CCR FROM DCEG, WAS TRAINED IN PREVENTION INITIALLY AND EPIDEMIOLOGY, HE'S FAIRLY INTEGRATED WITH DCE, LESS WITH DCP BUT WE'RE TRYING TO HAVE DISCUSSIONS. THE BIGGEST THING IS WHAT MAKES SENSE FOR THEIR PORTFOLIO THAT WOULD BE COMPLIMENTARY WE HAVE TO BE CAREFUL, WE'RE NEVER GOING TO DO BIG PRESCRENGS STUDIES. WE NEED TO DO PILOT STUDIES THAT WILL THEN BE SOMETHING THAT CAN BE TAKEN. >> THAT'S WHERE THE FIELD IS GOING TO DO EARLY PHASE PREVENTION STUDIES BEFORE GOING TO THE LARGE TRIALS. >> WE'RE RIGHT AT A LITTLE AFTER 2 O'CLOCK. SO THANKS VERY MUCH LEE. THE NEXT PRESENTATION IS AN UPDATE FOR THE COMMITTEE, ONE OF THE FIRST COMMITTEES IF NOT IF FIRST SUBCOMMITTEE FORMED WAS A GUIDELINES HARMONIZATION GROUP, THIS IS A LOOK AT THE GUIDELINES ACROSS THE COOPERATIVE GROUPS, SPORES AND CANCER CENTERS TO TRY TO INCREASE COLLABORATION BETWEEN THESE MAJOR PROGRAMS A LOT OF EFFORT HAS GONE INTO THIS AND PROGRESS MADE AND WHAT WE WANT TO DO TODAY IS UPDATE SOME OF THAT AND SO ANNA LEVEE WILL START AND THEN TONY HECHT WILL TALK ABOUT WORK DONE WITH THE SPORE GUIDELINE. >> SO GOOD AFTERNOON AND THANK YOU FOR THIS OPPORTUNITY TO GIVE YOU A SHORT UPDATE ON SOME OF OUR PROGRESS. SINCE WE PRESENTED THE ORIGINAL REPORT AND I GUESS ABOUT TWO YEARS AGO THEN THE IMPLEMENTATION PLAN LAST YEAR AROUND THIS TIME WE THOUGHT IT MIGHT BE HELPFUL TO REFRESH PEOPLE'S MEMORIES AB THE REPORT AND FOR SOME OF YOU WHO WEREN'T ON THE COMMITTEE AT THAT POINT. YOU DO HAVE A COPY OF THE IMPLEMENTATION PLAN IN YOUR BOOKS AND THE ORIGINAL REPORT IS UP ON THE WEBSITE SO I WON'T GO INTO A LOT OF DETAIL. JUST THE WORK OF THE GROUP, THE GOAL WAS TO HARMONIZE GUIDELINES AND DEVELOP INCENTIVES TO FOSTER COLLABORATIONS AND COLLABORATIVE TEAM SCIENCE. AND THE SUPPORT OUR ULTIMATE GOAL OF FULLY INTEGRATED TRIAL SYSTEM. (INDISCERNIBLE) WAS CHAIR OF THE WORKING GROUP, WORKED ABOUT A YEAR, YEAR AND A HALF AND THERE WERE MEMBERS FROM CTAC ON THE COOPERATIVE GROUP SPORE CANCER CENTERS AND THE NCI LEADERSHIP. AND OVER A PERIOD OF MONTHS WE DEFINED COLLABORATION, IDENTIFIED SOME MILD COLLABORATIVE EFFORTS SUCH AS SELECT I SPY AND DEVELOPMENT OF (INDISCERNIBLE) AND THERE ARE PROBABLY OTHERS OF COURSE SINCE THAT REPORT CAME OUT. AND TO LOOK AT LESSONS LEARNED ON WHAT WERE CHALLENGES AND COLLABORATIVE EFFORTS. THEN THEY LOOKED CAREFULLY AT WHAT WERE IN THE CURRENT GUIDELINES FOR THE MAJOR MECHANISMS IN THE CLINICAL TRANSLATIONAL RESEARCH INFRASTRUCTURE WHAT ARE DISINCENTIVES AND BARRIERS ACROSS MECHANISMS AND IDENTIFIED THAT THE DISINCENTIVES GUIDELINE ALLOWING SPECIFITY IN THE GUIDELINES FOR GRANTEES AND ON THE REVIEWERS DIFFERENCES IN ORGANIZATIONAL CULTURES THAT IN FISCAL REALITIES THAT ARE CHALLENGES TO THOSE COLLABORATIVE EFFORTS. CHALLENGES ARE DESCRIBED IN MORE DETAIL IN THE REPORT. FINALLY WORKING GROUP DEVELOP RECOMMENDATIONS AN IMPLEMENTATION PLAN WAS PRESENTED IN THE LAST YEAR TO CTAC. THE RECOMMENDATIONS FALL INTO TWO BROAD AREAS, ONE IS PROVIDING THE GUIDELINES AND THE REVIEW CRITERIA WHICH IS CRITICAL FOR THE THREE MAJOR CLINICAL TRIALS MECHANISMS, SPORES CANCER CENTERS AND COOPERATIVE GROUPS AND THOSE ARE THE MECHANISMS WHICH HAVE STANDALONE PROGRAMS THAT -- AND THEN THE SECOND AREA WAS TO FOSTER -- PROVIDE INCENTIVES TO COLLABORATION SO TOE TOBY WILL GIVE Y AN UPDATE TO REVISED GUIDELINES THAT WENT INTO EFFECT AUGUST OF THIS YEAR. THEN THE SECOND AREA INCENTIVES TO COLLABORATION, THERE ARE A NUMBER OF INCENTIVES TO COLLABORATION WERE RECOMMENDED AND DESCRIBED IN THE IMPLEMENTATION PLAN. AND THIS MORNING DR. DOROSHOW MENTIONED PROGRESS IN THE INVESTIGATOR TEAM LEADERSHIP AWARD AND THE CTSU OPPORTUNITY. DR. HECHT WILL UPDATE YOU ON ACTIVITIES RELATED TO THE ORGAN SITE SPECIFIC MEETINGS AND TO THE ARRA FUNDED GO GRANTS PILOT MECHANISM TO SUPPORT TEAM SCIENCE AS WE MOVE FORWARD WITH CANCER SENOR GUIDELINE AN COOPERATIVE GROUP GUIDELINES WE WILL PROVIDE MORE FUTURE UPDATES. >> SO LAST DECEMBER I PRESENTED TO YOU HOW THE SPORE PROGRAM WOULD IMPLEMENT THE GUIDELINE RECOMMENDATIONS OF THE WORKING GROUP. TODAY I'M GOING TO TELL YOU WHAT WE DID LAST DECEMBER WAS THE STARTING LINE AND NOW WE HAVE ARRIVED AT THE FINISH LINE FOR THE NEW SPORE GUIDELINES. SO THE WORKING GROUP REPORT RECOMMENDED THE FOLLOWING. COLLABORATIVE EFFORTS ACROSS MECHANISMS SHOULD BE DESCRIBED IN A SPECIFIC SECTION OF THE APPLICATION. SO WE TOOK THIS TO HEART AND DEVELOPED AND INDEPENDENT SECTION OF THE SPORE APPLICATION CALLED SCIENTIFIC COLLABORATIONS. AND THIS SECTION INCLUDES A DESCRIPTION OF COLLABORATIVE EFFORTS THAT HAVE AS THEIR GOAL MOVING STUDIES FROM THE EARLIEST STUDIES OF DEVELOPMENT IN CANCER THERAPEUTICS, BIOMARKERS, PREVENTION, EPIDEMIOLOGY, FROM DISCOVERY, EARLY CLINICAL STUDIES AN LATER STAGE STUDIES AN BEYOND. THIS SHOULD TAKE PLACE EITHER WITHIN THE SPORE COMMUNITY OR ACROSS NCI SUPPORTED CLINICAL TRIALS AND TRANSLATIONAL SCIENCE MECHANISMS AND ALSO WITH OTHER GOVERNMENT AND NON-GOVERNMENT PROGRAMS. THE SECTION ALSO SHOULD DESCRIBE LEADERSHIP RELATED TO COLLABORATION AND INCLUDE A DESCRIPTION OF COLLABORATIVE ARRANGEMENTS WHERE APPROPRIATE SUCH AS SEPARATE GRANTS THAT'S GOING TO CONTINUE SOME OF THE WORK IN THE SPORE, CONTRACTS OR CREDAS WITH INDUSTRY, AND CONTINUE DEVELOPMENT OF CONCEPTS THAT ORIGINATE IN THE SPORES. SO TRANSLATIONAL RESEARCH IS BEST SERVED BY DEFINING TWO TYPES OF COLLABORATION. THE FIRST IS THE HORIZONTAL COLLABORATION WHERE GROUPS WORK TOGETHER TO ACCOMPLISH RESEARCH AIMS OR GOALS ON SINGLE LEVEL. THAT IS IN THE LABORATORY OR IN THE CLINIC OR IN A POPULATION CLINICAL STUDY. THAT'S TRADITIONALLY WHAT SPORES HAVE BEEN DOING FOR YEARS. WE INCLUDED VERTICAL COLLABORATION WHERE GROUPS WORK TOGETHER SEQUENTIALLY OR WITH OVERLAP TO MOVE UP THE TRANSLATIONAL RESEARCH PATHWAY FROM DISCOVERY PRE-CLINICAL DEVELOPMENT TO PHASE 1 TRIALS OR STUDY, LATER PHASE STUDIES AN POSSIBLY TO A FINAL HAND-OFF TO A COMMERCIAL COMPANY. WE'RE ASKING EACH SPORE TO DEMONSTRATE A COMMITMENT TO BOTH HORIZONTAL AND VERTICAL COLLABORATION IN COMPLETING PRE-CLINICAL PROJECTS AND MOVING PROMISING RESULTS ALONG THE PATHWAY TO TRANSLATIONAL AND CLINICAL DEVELOPMENT. THE OTHER THING THAT THE WORKING GROUP REPORT SAID WAS THAT CREDIT SHOULD BE REFLECTED IN PRIORITY OR OVERALL IMPACT SCORE. THE FIRST THING IS THAT THIS SECTION, THE SECTION I JUST DESCRIBED IS GOING TO RECEIVE AN INDEPENDENT NUMERICAL SCORE OF 1 TO 9 JUST LIKE ANY RO-1 IN PEER REVIEW. BUT WE HAVE DONE MORE THAN THAT, WE HAVE NOW ASKED IT TO BE REFLECT IN THE OVERALL IMPACT SCORE. WE DID THAT BY SCORE ELIMINATING THE OLD 70/30 SCORING RAWSH OWE IN EFFECT. APPLIED HANDEDLY AND WE ALSO FELT MORE EMPHASIS NEEDED TO BE ON THE SCIENTIFIC PROJECT. SO INSTEAD NOW WE'RE ASKING REVIEWERS TO FOCUS ON TRANSLATIONAL IMPACT OF THE SCIENTIFIC RESEARCH PROJECTS AND THAT INCLUDES ANY COLLABORATION. SUPPORTED BY THE CORES IN THE CONTEXT OF THE PROGRAM ORGANIZATION AND CAPABILITIES. AND DEVELOPMENTAL PROGRAM AND SCIENTIFIC COLLABORATION PROCEDURAL SECTIONS OF THE SCORE. THE WORKING GROUP REPORT SAID COLLABORATIVE ACTIVITIES SHOULD BE BETWEEN THE PROGRAMS. MENTION TO YOU COLLABORATIVE ACTIVITY HAS BEEN A KEY FEATURE OF SPORES BUT WHEN REVIEWED IT WAS REVIEWED AS ONE OF SEVEN ELEMENTS IN THE PROGRAM ORGANIZATION AND CAPABILITY SECTION OF THE APPLICATION. AND NOW THAT THE SCIENTIFIC COLLABORATION SECTION IS GOING TO BE INDEPENDENTLY SCORED, IT WILL HAVE MORE WEIGH. THOUGH THIS IS NOTED IN GUIDELINES, WE HAVE OTHER WAYS OF SPORES ARE COLLABORATING. MOST SITES HAVE MONTHLY TELECONFERENCES FOR SHARING INFORMATION, DATA AND FOR INITIATING COLLABORATION. AND SOME OF THE INSTITUTIONS THAT HAVE SEVERAL SPORES HAVE INITIATED MEETINGS THAT CROSS THE ORGAN SITE, WHERE EXAMPLE SIGNALING PATHWAYS THAT ARE COMMON TO VARIOUS ORGAN SITES ARE DISCUSSED AND TECHNOLOGIES FOR EXAMPLE VIRUSES THAT RUS REPUBLICAN USED IN A NUMBER OF DIFFERENT ORGAN SITES, INFORMATION IS SHARED. ANOTHER REPORT RECOMMENDATION WAS TO INCENTIVIZE TRANSMIT COLLABORATIONS THAT WILL MOVE NOVEL INTERVENTIONS FROM PRE-CLINICAL TO EARLY CLINICAL TO STAGE 3 TRIALS. SO I SHOULD MENTION TO YOU THAT ONLY PHASE 1 AND EARLY PHASE 2 TRIALS ARE SUPPORTED BY THE SPORES. SO WHAT HAPPENS WHEN A REALLY GOOD SUCCESSFUL CONCEPT IS COMPLETED AT THAT POINT. WE NEED TO HAVE A MECHANISM TO HAND OFF. AND YOU HAVE HEARD THIS MORNING ABOUT VARIOUS MECHANISMS OF DOING THAT. FOR COLLABORATION WITH OTHER SPORES, CANCER CENTERS AND OTHER NCI GRANT MECHANISMS ON RANDOMIZED PHASE 2 THERAPEUTIC TRIALS, SPORES ARE BEING ADVISED TO USE THE APPROPRIATE NCI DISEASE-SPECIFIC STEERING COMMITTEES, AND TASK FORCES TO WORK TOGETHER TO DEVELOP CLINICAL CONCEPTS FROM EARLY SPORE TRIALS THAT CAN BE MOVED FORWARD THE COOPERATIVE GROUPSCH THESE MAY INCLUDE RELATIVE STUDIES IN MANY CASES. AND ALSO WHEN THE STEERING COMMITTEE IS NOT ABLE TO USE THE COOPERATIVE GROUPS WE'RE PROMOTING A LIMITED ALTERNATIVE BUT LIMITED COLLABORATIVE OPPORTUNITY USING THE CTSU RESOURCES AND THAT WOULD BE ON RECOMMENDATIONS OF THE STEERING COMMITTEE. INFORMATION AND INSTRUCTIONS FOR THIS IS IN THE NEW GUIDELINES. THIS IS THE TIME LINE WE PUT FORWARD LAST DECEMBER. WE STAID WE WOULD START TO WRITE AND FINISH WRITING AND HAVE APPROVAL OF THE NEW GUIDELINES BY AUGUST OF 2011 AND IN FACT THAT'S EXACTLY WHAT HAPPENED. WE COMPLETED IT AND HAD APPROVAL IN AUGUST OF 2011. WE SAID WE WOULD HAVE THE PROGRAM ANNOUNCEMENTS COMPLETED AND APPROVED BY SEPTEMBER 2011 AND THAT IS WHAT HAPPENED. AND THE APPLICATION RECEIPT DATE IS JANUARY OF 2012 AND WE'RE EXPECTING LETTERS OF INTENT DUE IN DECEMBER. FOR FUNDING IN FY 2013 AND AT THE BOTTOM OF THE SLIDE IS THE LINK TO THE SPORE GUIDELINES. SO I WANT TO MOVE TO SECOND AREA, NOT ONLY CHANGING THE GUIDELINES FOR HARMONIZATION BUT ALSO HAVING INCENTIVES FOR COLLABORATION. THAT'S VERY DIFFICULT TO DO WITH A LARGE POT OF MONEY AS Y'ALL KNOW. BUT SOME OF THE THINGS WE CAME UP WITH ARE ACTUALLY WORKING VERY WELL. ONE OF THE THINGS IS TO ESTABLISH ORGAN SITE WORKSHOPS. THE GOAL OF THESE WORKSHOPS PROVIDE VENUES IN ALL AREAS OF TRANSLATIONAL RESEARCH TO COME TOGETHER IN SMALL GROUPS TO FOCUS ON NEW GOALS IN TRANSLATIONAL SCIENCE. THE IDEA HERE IS TO FACILITATE INVESTIGATOR INITIATED INTERACTIONS TO FOSTER COLLABORATION ACROSS GRANT MECHANISMS TO FORGE NEW COLLABORATIONS OR TO CONSOLIDATE ONES JUST STARTED. HOWEVER CONDITIONS FOR APPLYING FOR THESE WORKSHOPS WERE STRICT. THEY HAD CO-CHAIRS FOR MORE THAN ONE NCI SUPPORTED MECHANISM AND ACTIVE FUNDING WAS REQUIRED. IT NEEDED TO HAVE A UNIQUE COLLABORATIVE PURPOSE WITH FOLLOW-UP, IT HAS STATED OBJECTIVES IN OUTCOMES ALIGNED WITH SCIENTIFIC PRIORITIES OF THAT SPECIFIC ORGAN SITE@8 AND AT A SIMILAR MEETING COULD NOT BE SCHEDULED IN THAT ORGAN SITE IN THE NEAR FUTURE OR IN THE PAST AND OUTCOMES REPORTED BY THE CORE CHAIR. SO THE SUMMARY OF WHAT HAS HAPPENED IN THE LAST YEAR IS THAT WE HAVE HAD 10 APPLICATIONS, AND THREE OF THEM HAVE GONE FORWARD FOR APPROVAL. AND ONES LISTED HERE ARE THE ONES THAT WERE APPROVED, THE PROSTATE CANCER GENETICS WORKSHOP WHICH TOOK PLACE LAST YEAR, TARGETING LYMPHOMA, METABOLISM AND ONCO GENIC PATHWAYS WHICH TOOK PLACE IN JULY IN CONJUNCTION WITH THE TRANSLATIONAL SCIENCE MEETING. AND ONLY IN SEPTEMBER DID WE HAVE THE NOVEL NEW ADJUVANT THERAPY FOR BLADDER CANCER MEETINGS. AND THOUGH I WON'T GO THROUGH EACH OF THESE ACCOMPLISH I'M GOING TO TELL YOU A LITTLE BIT ABOUT WHAT HAPPENED IN THE PROSTATE CANCER GENETICS WORKSHOP, THAT WAS A YEAR AGO. THIS WORKSHOP WAS CHAIRED BY BILL CATALONA AND ISAACS. AND THE PURPOSE WAS TO BRING TOGETHER EXPERTS IN THE FIELD OF PROSTATE CANCER GENETICS TO DEVELOP A STRATEGY TO STUDY THE GENETICS OF A AGGRESSIVE PROSTATE CANCER. A SECONDARY GOAL WAS TO DISCUSS CONSISTENCY IN DATA COLLECTION. AND PARTICIPANT CAME FROM LOTS OF DIFFERENT BACKGROUNDS. THERE WERE UROLOGISTS, MEDICAL ONCOLOGIST, GENETICISTS, EPIDEMIOLOGISTS AND STATISTICIANS AND THE NCI STA WAS ALSO INVITED TO PARTICIPATE. IF YOU LOOK AT FUNDING FOR THESE INVESTIGATORS THEY WERE ALL OVER THE PLACE. SPORES, NHGRI, EDRN, THE INTERNATIONAL CONSORTIUM OF PROSTATE CANCER GENETICS, THE PROSTATE CANCER FOUNDATION, AND MED TAP. THERE WAS A PLAN FOR A MULTI-COLLATERAL INSTITUTION FOR ACQUISITION AND ANALYSIS FOR DATA FOR CASE ASSOCIATION STUDY TO IDENTIFY SNP THAT'S ARE ASSOCIATED WITH AGGRESSIVE PROSTATE CANCER. THE MEETING REPORT WAS PUBLISHED LAST MAY AND THERE'S STILL ?ROAUP ACTIVITIES. THE FOLLOW-UP ACTIVITIES ARE MORE FORMALIZED NOW, THERE'S A GENETICS WORKING GROUP THAT WAS FORMED, 23,000 CASES THAT ARE LEFT FOR ANALYSIS BOTH AFRICAN AMERICANS AN CAUCASIANS HAS BEEN ACCESSED. AND THERE ARE 35 SNP THAT'S HAVE BEEN IDENTIFIED. AND ANALYSIS IS ONGOING. SO NOW I'M GOING TO CHANGE GEARS A LITTLE BIT AND TALK TO YOU ABOUT THE GRANT OPPORTUNITY GRANTS AS A MODEL MECHANISM FOR TEAM SCIENCE RESEARCH. I DON'T KNOW IF YOU REMEMBER WHAT HAPPENED AT THE TIME OF THE AMERICAN RECOVERY AND REINVESTMENT ACT WHEN THERE WAS QUITE A BIT OF MONEY THAT CAME IN TO THE INSTITUTE BUT WE PUT TOGETHER INCENTIVE FOR COLLABORATIONCH THAT WAS DISCUSSED IN THE WORKING GROUP REPORT. WHICH SAID WHICH WOULD ON THE GO GRANTS FOR CLINICAL TRANSLATIONAL RESEARCH AND EVALUATE THE EFFECTIVENESS OF GO GRANTS ENTITLED COORDINATION OF CLINICAL TRANSLATIONAL RESEARCH ACROSS THE NCI. WITH THE INTEND OF DEVELOPING SIMILAR GRANTS AND USE IT AS A MODEL TO DEVELOP A NEW MECHANISM TO MOVE EXCITING NOVEL AND CLINICALLY APPLICABLE IDEAS FROM BENCH TO BEDSIDE THROUGH THE CLINICAL TRIAL SYSTEM TRANSCENDING CULTURAL BARRIERS AND RESEARCH SILOS,S THAT TAKEN VERBATIM FROM THE REPORT. NOW, AT THE TIME THAT THE GO GRANTS WERE PUT OUT ON THE STREET THERE WERE SOME STRICT QUALIFICATIONS THE PIs HAD TO BE FROM DIFFERENT INSTITUTES WITH DIVERSE EXPERTISE, WHO ARE ALREADY SUPPORTED BY DIFFERENT NCI OR NIH FUNDING MECHANISMS. THEY FORMED A TEAM WITH INTENSIVE HIGH IMPACT AND IF POSSIBLE, PARADIGM SHIFTING STUDIES THAT WERE ASSOCIATED WITH CLINICAL TRIALS. THEY NEED TO PROPOSE TRANSLATIONAL CANCER RESEARCH PROJECT OF SIGNIFICANT SCOPE AND CONSEQUENCE THAT -- AND THIS IS BECAUSE OF THE ARRA AWARD, HAD TO BE COMPLETED WITHIN TWO YEARS.xf AND I EAT GET IN MINUTE WHY THAT WASN'T OPTIMAL. THEY HAD TO FORM GIVEN HYPOTHESIS DRIVEN CORRELATIVE STUDIES ASSOCIATED WITH ONGOING CLINICAL TRIAL OR NEW READY TO PROCEED CLINICAL TRIAL IN A MULTI-INSTITUTIONAL SETTING. INDUSTRIAL AND FOUNDATION PARTNERS WERE ALLOWED TO PARTICIPATE IN THE RESEARCH BUT WERE NOT GIVEN GOVERNMENT SUPPORT TO THE STUDIES. SO THE RESULTS OF THE GO GRANT INITIATIVE WERE THAT WE RECEIVED 32 APPLICATIONS, NINE WERE FUNDED. THEY TRANSSENNED THE NCI PROGRAMS AN DISEASES, IF YOU LOOK ON THE RIGHT SIDE YOU CAN SEE THERE WAS A REAL WIDE ARRAY OF DISEASES THAT WERE REPRESENTED BY THE GRANTS THAT WERE FUNDED. PANCREATIC CANCER, CHILDHOOD ALL, SARCOMA, GLIOBLASTOMA, LUNG CANCER, PROSTATE, LEUKEMIA, ORAL CANCER, AND MELANOMA, SO WHAT IS THE STATUS NOW OF THE GRANTS THAT HAVE ALREADY HAD TWO YEARS OF FUNDING? NONE OF THOSE GRANTS OF THOSE NINE GRANTS HAVE BEEN COMPLETED. SO EACH GRANT HAS NOW BEEN GIVEN A ONE YEAR NO COST EXTENSION, NO ADDITIONAL COSTS ASSOCIATED WITH THIS BUT MANY OF THEM NEEDED THAT EXTRA YEAR. SO PROGRESS REPORTS ARE DUE AT THE END OF THE NO COST EXTENSION SO A FULL EVALUATION IS NOT POSSIBLE UNTIL ALL THE GRANTS ARE COMPLETED BUT I WANTED TO GIVE YOU A SHORT SYNOPSIS OF SOME OF THE WORK, I'M NOT GOING TO GIVE YOU DATA BUT I'LL GIVE YOU A SUMMARY OF THE GRANTS THAT HAVE BEEN ONGOING. I'M SURE THAT'S NOT TOO EASY TO READ BUT I THINK IT'S IN YOUR BOOK. THE FIRST ONE IS DR. TIMOTHY TRISH, PREDICTIVE CANCER BIOMARKERS INTO CLINICAL PRACTICE. WHAT IS THE PROBLEM ADDRESSED? IN THAT RHABDOMYOWE SARCOMA, PATIENTS ARE CLASSIFIED AT THE TIME OF DIAGNOSIS INTO RISK CATEGORY, HIGH, LOW AND INTERMEDIATE. THESE RISK CATEGORIES ARE BASED ON CLINICAL AND PATHOLOGICAL CRITERIA. WHAT THE CATEGORY IS DETERMINES ON HOW PATIENTS ARE TREATED FOR PATIENTS THAT ARE CLASSIFIED AS INTEER MEDIATE RISK THE CRITERIA OFTEN FAILS TO PREDICT OUTCOME. SO DR. TRISH TOGETHER WITH ONE OTHER PI, GOT TOGETHER WITH A NUMBER OF INSTITUTIONS AND THE GOAL WAS TO DEVELOP DIAGNOSTIC GENE EXPRESSION PROFILE FROM PARAFFIN EMBEDDED TUMOR TISSUES CLINICAL CLASSIFICATION OF CLASSIC RHABDOMYOWE SARCOMA IN ORDER TO DETERMINE TREATMENT OPTIONS BECAUSE THE PATHOLOGY AND CLINICAL CRITERIA FAIL TO PREDICT OUTCOME IN MOST PATIENTS PARTICULARLY THOSE CLASSIFIED AS INTERMEDIATE RISK. SO WHAT HAVE THEY DONE? THEY NOW ANALYZED THE OUTCOME VERSES 1.4 MILLION RNA TRANSCRIPT EXPRESSION VALUES AND 167 CHILDHOOD RHABDOMYOWE SARCOMA CASES, CRG INTERMEDIATE RISK PROTOCOLS AN DERIVED MULTI-GENE BIOMARKER PROFILE THAT THEY FEEL PREDICT OUTCOME BETTER THAN THE CLASSICAL WAY OF PREDICTING. THE TISSUES THAT WE USE IN THIS CASE WERE FROZEN TISSUES. SO NOW WHAT HE WANTS TO DO IS TO TRANSLATE TWO -- MOST OF THESE GENE EXPRESSIONS WERE CODING AND NON-CODING RNAs. AND HE WANTS TO TRANSLATE THIS TO A FASTER PLATFORM THAT WORKS WELL ON ROUTINE FST SPECIMENS. SO IF YOU SELECTED THE NANOSTREAM PLATFORM, AS THE BEST TECHNOLOGY AND TRANSLATED THE PROGNOSTIC SIGNATURE TO CLINICAL ASSAY AND SHOWED EXCELLENT CORRELATION BETWEEN DATA GENERATED AT CHRN'S HOSPITAL OF LOSS -- CHILDREN'S HOSPITAL OF LOS ANGELES AN NATIONWIDE CHILDREN'S HOSPITAL IN OHIO. AND APPLICATION FOR CLIA CERTIFICATION IS BEING DONE AT BOTH LABS. HE IS ASSESSING THE RNA EXPRESSION IN 400 CORRESPONDING FSP TUMORS FROM THE COG PROTOCOL INTERMEDIATE RISK AND HE'S NOW REFINING THE PROGNOSTIC PROFILE BY DROPPING UNDERPERFORMING RNA AND HE'S EXPECTING TO BE ABLE TO DO THIS BY THE END OF THE YEAR. AND THEN WE'LL DO A PROSPECTIVE VALIDATION ON PATIENTS IN CRG BOTH LOW, INTERMEDIATE AND HIGH RISK THERAPEUTIC PROTOCOLS. THE NEXT EXAMPLE, IS DR. BRUCE TROCK, AT JOHNS HOPKINS UNIVERSITY. AND THE PROBLEM THAT HE IS DEALING WITH IS THAT SOME MEN WHO ARE DETERMINED TO HAVE A 3 PLUS 3 ON BIOPSY ACTUALLY HAVE A HIGHER SCORE WHEN THEY HAVE A RADICAL PROSTATECTOMY. SO DR. TROK AND HITS TEAM WANT TO DEVELOP A PANEL OF BIOMARKERS THAT DISTINGUISH THOSE WHO ARE THREE FROM THOSE WHO ARE FOUR. AND THIS IS A CRITICAL NEED TO INCREASE THE SAFETY OF PATIENTS WHO CHOOSE ACTIVE SURVEILLANCE AND WHO ARE DETERMINED TO BE GRADE 3 BUT MAY IN FACT BE GRADE 4. SO THE BIOMARKERS THAT HE IS LOOKING AT ARE MOLECULAR INDICES WITH CHROMOSOME INSTABILITY. SPINDLE CHECK POINT INTEGRITY, SENT TRASOME FUNCTION, PROLIFERATION, HYPOXIA, EPIGENETIC DNA DAMAGE RESPONSE. THE PREDICTIVE MODEL IS PROPOSED AND VALIDATED IN AN INDEPENDENT COOR. SO WHAT HE'S DONE SO FAR IS EXCISION 200 RADICAL PROS TECH TOMY -- PROS PROSTATECTOMY SPECIMENS OF A GLEASON SCORE OF 3 PLUS 3, 4 PLUS 4 AND 4 PLUS 3 AND 106 BIOPSY CORES WITH THE CORRESPONDING PROSTATECTOMY TISSUES. TISSUE MICRO ARRAYS HAVE BEEN COMPLETED, BIOMARKER ANALYSIS IS PERFORMED IN FIVE LABORATORIES TO FINE MARKERS THAT DISCRIMINATE GLEE SAN 3 FROM 4. BIOMARKER OPTIMIZATION ASSAY IS COMPLETE, ANALYSIS IS CONTINUING AND WILL BE COMPLETED BY THE END OF THE NO COST EXTENSION YEAR. NEXT EXAMPLE IS DR. STEVEN GRANT FROM VIRGINIA COMMONWEALTH UNIVERSITY. AND THE PROBLEM THAT HE IS LOOKING AT IS THE DIFFICULT REFRACTORY AML, HIGH RISK MDF AND OTHER IMMUNOLOGIC CANCERS THAT NEEDS NEW APPROACHES SO HE IS BASING HIS WORK ON PRE-CLINICAL MODELS THAT WERE DEVELOPED IN HIS LAB AND HE'S STUDYING THE ANTITUMOR ACTIVITY FOR COMBINATION INHIBITOR AND CARDIOSOME INHIBITOR, IN A CLINICAL TRIAL WE REFRACTORY AML, HIGH RISK MDF, CML BLAST CRISIS AND ALL PATIENTS. HE'S ALSO DOING PHARMACODYNAMIC STUDIES IN BONE MARROW AND PERIPHERAL BLOOD ON NF KAPPA B ACTIVATION, DOWN REGULATION OF NF KAPPA B DEPENDENT PROTEINS, UP REGULATION OF PRO APOT POP TOTTIC PROTEIN AND -- APOPTOTIC PROTEIN AN PROTEIN ACTIVITY. SO HIS PROGRESS IS THAT IT IS REALLY DIFFICULT FOR HIM TO GET STARTED BECAUSE OF THE CLINICAL TRIALS AGREEMENTS THAT HAD TO BE DONE BETWEEN TWO DIFFERENT COMPANIES BUT HE WAS ABLE TO COMPLETE THAT. AND INGD APPROVAL WAS OBTAINED. THE CLINICAL TRIAL OPENED IN MAY OF 2010, 16 PATIENTS HAVE BEEN ENROLLED IN THREE DIFFERENT LEVELS, AND HE'S READY TO ESCALATE TO THE FOURTH DOSE LEVEL AS OF ABOUT A WEEK OR SO AGO. NO DOSE LIMITING TOXICITIES HAVE BEEN ENCOUNTERED SO FAR, THIS ONE OBJECTIVE RESPONSE FOR STABLE DISEASE AND SEVEN PROGRESSIVE DISEASES. HE'S HAD OBSTACLES, SOME PATIENTS HAVE NOT MET THE CRITERIA FOR CORELLA STUDIES OR REFUSED SECOND POST TREATMENT BONE MARROW AND HE'S HAD THREE PUBLICATIONS IN THIS. THE NEXT EXAMPLE IS SUZANNE (INDISCERNIBLE) OF OHIO STATE UNIVERSITY, SHE IS A DENTIST WHOSE WORKING IN HEAD AND NECK TUMORS. SHE HAS BEEN ABLE TO TEAM UP WITH MEDICAL COLLEGE OF WISCONSIN AND THE PROBLEM THAT SHE'S ADDRESSING IS THE TREATMENT OF DISPLASTIC ORAL LESIONS BEFORE THEY ADVANCE TO ORAL CANCERS. SHE'S EXTENDING A PREVIOUS WORK AND PREVENTION TRIAL WITH FREEZE-DRIED BLACK RASPBERRY BIOADHESIVE GEL IN ORAL LESIONS WHICH SHOWED THAT ONE-THIRD OF THE PARTICIPANTS OR HIGHER RESPONDERS. AND IT TURNS OUT IT'S IN THE PREPARATION. AND SHE SUGGESTED THAT PATIENT SPECIFIC DIFFERENCES IN TARGET TISSUE ABSORPTION, METABOLIC ACTIVATION AND LOCAL RETENTION OF THE BLACK RASPBERRY CONSTITUENTS AFFECTED THE CHEMOPREVENTION RESPONSES. SO HER PROGRESS IS THAT ALL THE ASSAYS HAVE BEEN ESTABLISHED WHICH IDENTIFY IN PK PARAMETERS AND BIOACTIVATION PATHWAYS THAT ARE ACTIVE IN HUMAN ORAL MUCOSA SHE WAS ABLE TO GET IND DURING THIS PERIOD. A STUDY WITH NORMAL VOLUNTEERS WHICH SUPPORT DIFFERENCES LOCAL RETENTION IN ORAL MUCOSA. SHE STARTED HER ORAL CANCER CHEMOPREVENTION TRIAL AND HAS ALREADY ACCRUED 16 PATIENTS IN STUDIES TO DETERMINE LOSS OF HETERO ZYGOSITY INDICES AND P-16 METHYLATION AND COMPARING PRE-AND POST TISSUES ARE ONGOING. HISTOLOGY AND CLINICAL RESULTS ARE PROMISING. SHE'S ALREADY LINED UP TEN ADDITIONAL PATIENTS AND THEY'RE IN VARIOUS STAGES OF THE STUDY AT THIS TIME. ONE PATIENT RESOLVED CLINICALLY AND HIS LATE MICROSCOPIC DIAGNOSIS DECREASED AND SHE HAS PUBLISHED A PAPER THIS YEAR. AND FINALLY, A LAST EXAMPLE, DR. JED WALLCHECK AT MEMORIAL SLOAN-KETTERING, THE PROBLEM HE'S ADDRESSING IS THAT IPILIMIMAB WHICH AS YOU KNOW RECEIVED FDA APPROVAL THIS YEAR FOR ADVANCED MELANOMA, WHEN PATIENTS ARE TREATED WITH IT THEY NEED TO SHOW DELAY IN CLINICAL BENEFIT AND IT WOULD BE VERY NICE TO HAVE A BIOMARKER THAT'S PREDICTS FAVORABLE OUTCOMES, PARTICULARLY BECAUSE THE SIDE EFFECTS OF IPILIBIMAM CAN BE VERY SERIOUS. SO WOULD BE NICE TO KNOW WHO IS GOING TO RESPOND. HE'S TEAMED UP A NUMBER OF INSTITUTIONS AND THE GOAL HERE WAS TO ESTABLISH THE IMPORTANCE IT SHOULD SAY IMMUNITY, AS THE BIOMARKER IN THE IMMUNOTHERAPY OF METASTATIC MELANOMA WITH ANTI-CTLA SCORE ANN BODY. HIS PROGRESS IS THAT ALL THE PATIENTS TREATED WITH THE IPILIMIMAB BUT IN STUDIES IN ADVANCE PATIENTS HE FOUND THAT PATIENTS THAT HAD AN CANCER ANTIGEN IF YOU DIDN'T KNOW THAT, THOSE ANN GUYS, PEOPLE WITH THOSE ANN BODIES EXPERIENCE MORE FREQUENT CLINICAL BENEFIT AT WEEK 24 THAN SEER ROW NEGATIVE PATIENTS. THOSE ANTIBODIES CAME UP QUICKLY. REALLY QUICKLY, THERE WAS A TREND TOWARDS MORE FAVORABLE RESPONSES IN THOSE PATIENTS. THEN WHEN HE LOOKED AT THE SEER ROW POSITIVE PATIENTS HE FOUND INDUCTION IN PATIENTS WITH SPECIFIC CD8 POSITIVE T-CELL RESPONSES, CORRELATED WITH A BETTER CLINICAL RESPONSE PREPARED THE PATIENT WHOSE DID NOT HAVE THE T-CELLS SO B AND T RESPONSES TO IT MAY HAVE PREDICTIVE VALUE IN IPI TREATMENT AND CONTINUAL STUDIES, JUST TO TALK ABOUT THE CONCEPT FOR TEAM SCIENCE AND WHETHER THIS IS SOMETHING THAT MIGHT BE VIABLE TO SPAN OR TO CON OR TO EVOLVE INTO SOME OTHER TYPE OF CONCEPT THAT WE MIGHT USE, WHAT ARE THE BENEFITS OF THIS TYPE OF CONCEPT? THERE ARE FEW IF ANY MECHANISMS THAT REQUIRE COLLABORATION ACROSS INSTITUTIONS AN ACROSS METHODS OF GRANTS AND CONTRACTS FOR RARE CANCERS, THOSE UNDER-REPRESENTED IN THE NCI PORTFOLIO. FUNDING MECHANISMS DON'T COMMONLY SUPPORT BOTH CLINICAL TRIALS AND CORRELATIVE STUDIES. THESE STUDY COULD BE COMPLETED IN THREE YEARS. CERTAINLY NOT TWO YEARS AS WE SEE, NONE HAVE BEEN COMPLETED IN TWO YEARS, THREE IS LESS THAN THE AVERAGE RO-1. WE THINK THAT MIGHT BE SOMETHING TO TAKE INTO CONSIDERATION. IT'S A GRANT, NOT A SUPPLEMENT, IT'S BETTER THAN A SUPPLEMENT BECAUSE WHEN YOU HAVE A SUPPLEMENT, YOU HAVE TO HAVE GRANTS THAT HAVE ENOUGH YEARS LEFT IN THEIR FUNDING PERIODS TO BE ABLE TO GET THAT SUPPLEMENT. THEN IF YOU'RE COLLABORATING YOU HAVE TO HAVE INVESTIGATORS THAT ARE COMPLETELY IN SYNC WITH THEIR FUNDING PERIODS, MOST OF THE TIME THAT'S NOT THE CASE THAISM EAR OUT OF SYNC. -- THEY'RE OUT OF SYNC. INVESTIGATOR WHOSE ARE CO-PIRKSIs OR KEY PERSONNEL AND -- CO-PIs OR KEY PERSONNEL AND HAVE EXPERTISE NEEDED COULDN'T APPLY IN THIS CASE. SO THE QUESTION FOR YOU AND TO CONSIDER IS THAT IS THIS A MECHANISM THAT NCI SHOULD CONSIDER FOR THE FUTURE TO ENCOURAGE TEAM SCIENCE? AT THIS POINT I WILL STOP AND IF YOU HAVE ANY QUESTIONS OR WOULD LIKE TO DISCUSS, THAT'S GREAT. >> THANK YOU, I WANTED TO ASK KIM DOROSHOW TO COMMENT ON THE GO GRANTS. SEEMS WE HAVE HEARD COMMENTS BEFORE, GEORGE MENTIONED THIS MORNING MECHANISMS TO FACILITATE MORE TRANSLATIONAL SCIENCE, THAT SEEMS TO BE THE POTENTIAL GAP IN SOME OF THE THINGS WE'RE DOING. THIS MAYBE A MECHANISM TO HELP CLOSE THE GAP, PROVIDE FUNDING FOR THIS TYPE OF TRANSLATIONAL RESEARCH. JIM I DON'T KNOW IF YOU WANT TO MAKE ADDITIONAL COMMENTS. >> A IF ADDITIONAL PROJECTS THAT TONY DIDN'T PRESENT THAT ARE ENCOURAGING, BECAUSE THIS IS A WAY OF SUPPORTING BRINGING PEOPLE SUCCESSFUL PEOPLE TOGETHER WITH SUFFICIENT RESOURCES TO DO THINGS THEY COULDN'T OTHERWISE DO. AS TO WHETHER OR NOT THIS IS SOMETHING THAT -- IS IT SOMETHING WE SHOULD BE DOING INSTEAD OF SOMETHING ELSE? ARE THERE ENOUGH PROJECTS PER YEAR TO SUPPORT THE REVIEW NECESSARY? OR ARE THESE JUST RARE INSTANCES? I SAY IT'S PROBABLY THE FORMER, IT'S QUITE REMARKABLE THAT WE GAVE PEOPLE I'M SURE SOME OF YOU REMEMBER VIVIDLY WE GAVE PEOPLE ALMOST NO TIME TO WRITE THE GRANTS, SIX WEEKS FOR THE GO GRANTS, THEY HAD TO TURN AROUND MULTI-INSTITUTIONAL COLLABORATION. THEY WEREN'T ALL NECESSARILY AT THE TIME GRANTS WERE DUE YET WE HAD A REALLY LARGE NUMBER OF INTERESTING PROPOSE LALS SO -- PROPOSALS SO IT'S SOMETHING FOR US TO CONSIDER. >> ANYTHING WE CAN DO TO ENCOURAGE COLLABORATION, I WONDER IF WE NEED A NEW MECHANISM OR IS TOBY COMMENTED SOUNDS LIKE THE SPORES ARE PUTTING IN CERTAINLY INCENTIVES. IT'S NOT A REQUIREMENT CERTAINLY TAKEN SERIOUSLY YOU CAN DO IT WITHIN AN ESTABLISHED PROGRAM PERHAPS. AND I WAS GOING TO ASK TOBY A QUESTION. ON THE HAND OFFS IN THE NEW GUIDELINES, WE SHOULD KNOW THIS BUT ON THE INTERVENTIONS DEVELOPING PHASE # AND 2 AND HANDING OFF TO COOPERATIVE GROUPS OR INDUSTRY, DO THE GUIDELINES ALSO LOOK AT HAND-OFFS OF PREDICTIVE MARKERS, BIOMARKERS IN EARLY PHASE TRIALS FOR LATER SETTINGS COOPERATIVE GROUP AND INDUSTRY? >> SOME OF THE COOPERATIVE GROUP PROPOSALS WOULD INCLUDE CORRELATIVE STUDIES AND THAT COULD BE BIOMARKER STUDIES. FOR STAGE 3 BIOMARKER STUDIES THERE ARE OTHER MECHANISMS THAT WHEN YOU'RE READY FOR THAT YOU CAN APPLY FOR THAT AS WELL. THIS IS ONE OF THOSE. >> WHAT I WAS TRYING TO GET, A LOT OF SPORES, ARE TRYING TO DEVELOP POTENTIAL PROMISING PREDICTED BIOMARKERS, THEN NEED TO BE VALIDATED IN PHASE 3 TRIALS. IS THAT THE SAME WAY IN THE NEW GUIDELINES DEVELOPING A NEW AGENT THAN TAKEN AS A HAND OFF FOR LATE ?ER >> ABSOLUTELY, WHAT HAPPENS IS EVEN THOUGH A BIOMARKER IS DEVELOPED IT NEEDS TO GO NEXT STEP WITH ASSAY VALIDATION BEFORE IT HAS CLINICAL VALIDATION. SO THERE'S A CHUNK THAT HAS TO BE MET BEFORE IT CAN GET TO THAT NEXT STAGE. AND WE DO HAVE NOW THE CLINICAL ASSAY DEVELOPMENT PROGRAM THAT LOOKS AT THAT. I HAVE MENTIONED THAT ON A NUMBER OF TELECONFERENCE CALLS AND I WOULD LIKE TO SEE PEOPLE APPLY FOR THAT BECAUSE I KNOW THERE ARE VERY PROMISING BIOMARKERS THAT ARE COMING ALONG AND BENEFIT FROM USING NCI RESOURCES FOR THAT. >> I WAS ONE OF THE AUTHORS OF ONE OF THOSE INCREDIBLY WORTHY APPLICATIONS THAT WERE NOT SELECTED. WE JURIED ON THIS BECAUSE IT'S A WONDERFUL MECHANISM WITH A LOT OF FLEXIBILITY AND ALLOWS TRANSLATIONAL RESEARCHERS TO THINK OUT OF THE BOX IN A WAY THAT A LOT OF THE OTHER THINGS THAT WE HAVE THE ABILITY TO RESPOND TO DON'T. FOR US WE HAVE BEEN BATTING AROUND THIS IDEA FOR A LONG TIME AND IT WAS A REALLY GOOD IDEA. AND THIS GAVE US AN OPPORTUNITY TO DO IT SHORT TIME FRAME MADE US GET OFF THE DIME AND GET IT DONE TOO. I WOULD ARGUE IN FAVOR THIS IS A GOOD MECHANISM. >> WE WERE LIMITED BY THE MONEY WE SET ASIDE, THERE WERE SOME REALLY FABULOUS, JUST FABULOUS PROPOSALS THAT WE REALLY COULDN'T GET TO. >> MUST HAVE BEEN BEEN TWO OR THREE. >> ONE POINT I THINK THERE ARE TWO -- I LIKE THE CONCEPT BUT THERE ARE TWO SEPARATE ISSUES. AND THEY'RE DISTINCT AND THINKING ABOUT IT WE SHOULD SEPARATE THOSE ISSUES. ONE IS A COLLABORATION ISSUE AND THE SECOND IS THE CORRELATIVE SCIENCE ISSUE. AND THEY'RE BOTH EXTREMELY IMPORTANT BUT I DON'T THINK YOU NECESSARILY WANT TO ROLE THEM INTO ONE. I THINK THAT WOULD BE -- I WOULD BE CAREFUL BEFORE NECESSARILY ROLLING THEM INTO ONE, MAYBE THE RIGHT WAY TO GO BUT YOU MAY WANT TO SEPARATE OUT THOSE TWO ISSUES. I THINK SOMEONE SHOULD MOVE FORWARD TO MOVE CAREFULLY ABOUT HOW TO COMPLIEN THE SEPARATE ISSUES. NANCY THEN MOVE ON TO PROVOCATIVE. NANCY, TWO MORE QUESTIONS. >> THIS IS GREAT. I HATE TO SEE MONEY GET CUT FROM THE CLINICAL PROGRAM. THE NATIONAL CLINICAL TRIAL NETWORK PROGRAM. TO DO THINGS LIKE THIS. MAYBE SOME OF THE RO-1s COULD BE MOVED OVER TO THIS TYPE OF FUNDING, THAT WOULD BE REALLY COOL. ALL RIGHT. >> WE'LL GET RIGHT ON THAT. WITH ALL THE ARRA FUNDING SHORT DURATION, IT WOULD BE NICE TO HEAR IN A COUPLE OF YEARS, YOU HAVE ONE YEAR EXTENSION, COME BACK A COUPLE OF YEARS AND SAY DID THE COLLABORATIONS HAPPEN, THE PUBLICATIONS HAPPEN AND ALL THIS STUFF SO REMEMBER IN A COUPLE OF YEARS TO LET US KNOW. >> NANCY'S COMMENT MADE ME THINK OF THAT AND I STARTED TO COMMENT ABOUT USING SPORES ESTABLISHED PROGRAMS INCENTIVIZING THEM FOR COLLABORATIONS AND I GUESS I THROW IT OUT THERE THAT YOU HEARD FROM JIM PROGRAMS MAYBE CUT COMPLETELY SO DO WE WAN TO BE ESTABLISHING NEW PROGRAMS OR INCENTIVIZEING THE CURRENT ONES. >> OKAY. THANK YOU FOR THE DISCUSSION. WE'RE GOING TO MOVE ON TO THE PRETTY MUCH LAST PRESENTATION AND THAT'S DR. ED HARLOE WHO IS GOING TO UPDATE ON THE STATUS OF THE PROVOCATIVE QUESTIONS INITIATIVES. I HOPE YOU HAVE HAD A CHANCE TO LOOK AT THE QUESTIONS ON THE WEBSITE, A SERIES OF REALLY INTERESTING ISSUES AND HOPEFULLY WE'LL GET SOME UPDATE ON WHERE THIS WHOLE PROCESS ENDS. (OFF MIC) >> BETTER? THANKS VERY MUCH. YOU OFTEN YOU ASK -- THIS IS AN INFORMATIONAL SESSION, THERE ARE COMMENTS AND QUESTIONS AND DEEP PENETRATING CRITIQUES ARE IMPORTANT BUT AT THIS POINT I THINK IS A CHANCE FOR YOU TO RELAX AT THE END OF THE DAY AND TO HEAR ABOUT AN UPDATE. IT'S A CELEBRATION OF QUESTIONS. WITH THE TWIST OF THINKING HOW WE CAN BEST USE RESEARCH QUESTIONS IN OUR COMMUNITY. THAT'S WHAT WE'RE TALKING ABOUT TODAY. GRAB A FEW QUOTE, APOLOGIZE FOR THOSE WITH A FEW PEOPLE WHO THOUGHT ABOUT QUESTIONS IN DIFFERENT WAYS THROUGHOUT THE YEARS TRYING TO GRAB AND UNDERSTAND HOW THEY CAN BE USED IN OUR SETTING. WE USE QUESTIONS FOREVER AND HONORED THEM HIGHLY IN SCIENCES IN YOUR SETTINGS. MOST IS ORGANIZED AROUND THE THAT QUESTION. MY LAB BOOK -- MANY TIMES ANYWAY START ON THE TOP WITH A QUESTION OF WHAT I WAS UP TO FOR THAT DAY OR THAT WEEK AND THAT SETTING AND I THINK WE USE THAT AS AN ORGANIZATIONAL STRATEGY FOR ALL PARTS OF OUR SCIENTIFIC ENTERPRISE. YOU ALSO REALIZE THE QUESTION IS PART OF SCIENTIFIC RIGOR. THE BEST PART OF A TALK IS THAT PENETRATING QUESTION THAT COMES AFTERWARDS. AND SOMETIMES THE REVIEW OF YOUR GO GRANTS, REVIEW NUMBER 3 YOU ASK THAT, THAT REALLY CRITICAL QUESTION THAT KIND OF TIGHTENS OUR THINKING AN PUSHES US FORWARD. WHAT WE WANT TO TALK ABOUT TODAY IS THE DIRECTION. AND IT'S NOT SOMETHING PART OF OUR OPERATION EXCEPT IN AN ABSTRACT WAY BUT IN THIS PARTICULAR PROJECT IS VERY MUCH THE CENTER OF OUR WORK. SO LET ME TELL YOU ABOUT PROVOCATIVE QUESTIONS, HOW THEY STARTED, HOW THEY DEVELOPED. IT'S REALLY A SENSE OF ASKING THE COMMUNITY TO HELP SET QUESTIONS OF INTEREST FOR OUR ATTENTION. IT REALLY HAS FOUNDATIONS AND A NUMBER OF QUESTIONS BUILDING OPERATIONS OF YOU ARE TIME. I THINK HAROLD VARMUS AND I WERE INFLUENCED BY THE GATES FOUNDATION GRAND CHALLENGES THAT CAME OUT SOME YEARS AGO THAT REALLY BEGAN TO TRY AND FRAME NUNTS SCIENCE BY TALKING TO THE IMMUNITY SAYING WHERE DO WE NEED TO GO, IN THAT CASE TRYING TO THINK ALL LITTLE BIT ABOUT WHAT HAD TO HAPPEN IN GLOBAL HEALTH. WHAT WERE THE KEY ISSUES. A PARTICULAR OPERATION WAS NOT DIRECTED AT QUESTIONS, IT WAS DIRECTED AT PROJECTS AND GOALS. IN THAT SETTING, QUESTIONS HAVE TO BE THE KEY FOUNDATION FOR ALL OF OUR THINKING. WE SET THE QUESTIONS TO TRY TO BE AS MUCH AS WE CAN INTO AREAS THAT ARE OBVIOUS. WHEN LOOKING FOR AREAS OF RESEARCH THAT ARE JUST MAYBE COULD BE POSSIBLE NOW BECAUSE OF NEW TECHNOLOGY DEVELOPMENTS, AND IN SOME CASES THESE MAYBE NEW AREAS THAT HAVE BEEN OR MIGHT BE AREAS FORGOTTEN FOR DECADES. ISLE SHOW YOU AN EXAMPLE AS WE GO THROUGH BUT THERE ARE WAYS TO LOOK FOR PLACE WHERE IS WE DON'T HAVE THE LIGHT WELL SHOWN, WHERE WE'RE NOT PAYING ATTENTION IN THAT SETTING. THAT'S A FOUNDATION THERE SO THERE HAVE TO BE QUESTIONS IN AREAS NOT WORKING DIFFICULT, THEY THOB BUILDING FROM WHERE WE ARE TO MOVE FORWARD. THEY ADDRESS BROAD ISSUES AND THE BIOLOGY OF CANCER, DIFFICULT TO RESOLVE, THERE MUST BE IN OUR DEFINITION OF PROVOCATIVE QUESTIONS HAVE TO BE ISSUES THAT ARE ACHIEVABLE. SO LOTS OF GOALS WE WANT TO HEAD TOWARD, LOTS OF QUESTIONS WE IMAGINE FRAMING THAT WE CAN'T APPROACH AT THE MOMENT. YOU HAVE TO HAVE THE FRAMEWORK WHERE THEY'RE IN OUR GRAPH AND THEY HAVE A CHANCE TO OVERCOME OBSTACLES AS WE GO THROUGH. THIS WHOLE OPERATIONAL IS AN EMPERIMENT. I WILL'S STILL AN EXPERIMENT. YOU THINK TELL FROM MY ENTHUSIASM, I THINK THE EXPERIMENT IS WORKING. WE DON'T KNOW THE ANSWER LONG TERM A COUPLE OF YOU WERE INVOLVED IN A NUMBER OF OUR WORKSHOPS ON THE OPENING DAYS OF THIS OPERATION. LAST YEAR IN OCTOBER REALLY FRIENDS OF HAROLD'S WORKSHOP, IT WASN'T VISITATION THAT WHEN OUT TO LEADERS IN OUR IMMUNITY WHO CAME HERE TO THE CAMPUS AND THE REAL QUESTION IN THIS FIRST WORKSHOP WAS COULD WE ACTUALLY FIND SUBJECTS OR QUESTIONS THAT SEEMED TO WORK IN THIS AREA. COULD THEY IDENTIFY USEFUL QUESTIONS THAT AN AREA THAT NEEDED TO BE DEVELOPED IN THAT SETTING. AND ANOTHER IMPORTANT PROCESS OF THIS QUESTION, WAS THE PROCESS FUN WOULD THE COMMUNITY ENJOY THE BANTOR AROUND ESTABLISHING QUESTIONS AND THE ANSWER ON BOTH FRONTS WAS YES. WE WERE ABLE TO IDENTIFY INTERESTING QUESTIONS AND EVERYBODY HAD A GOOD TIME COMING TO IT. YOU CAN IMAGINE SITTING AROUND THE TABLE WITH A BUNCH OF COLLEAGUES, BUT CONSIDER FIGHTING THE NEXT PART OF OUR EXPERIMENT WAS COULD WE ESTABLISH A LARGE GROUP OF QUESTIONS THAT BEGAN TO FIT INTO THIS TOP LEVEL. SO WE GOT A SERIES OF WORKSHOPS OVER THE LAST MONTH, FEBRUARY WE RAN THREE WORKSHOPS, DIVIDED BY DISCIPLINES SO WE HAVE A PUFF SCIENCE GROUP, A CLINICAL SCIENCE GROUP AND A BASIC SCIENCE GROUP. EVERYBODY CAME O THE CAMPUS HERE AND WE FOUGHT FOR A DAY ABOUT IDEAS AND QUESTIONS, IN FACT, FOUND THAT IT WAS REALLY A DEEP SETTING. WE MOVED THE WORKSHOP ON THE WEST COAST FOR WITH PEOPLE FROM THE LOCAL AREA, ONE IN SAN DIEGO, ONE LA, SAN FRANCISCO TO SEATTLE. THE SEATTLE GROUP IS IN THAT GROUP AS WELCOMING THROUGH. INTERESTINGLY IN EVERY ONE OF THOSE SESSIONS NEW QUESTIONS KEPT COMING OUT. SO IMAGINE IT'S LIKE I WAS WARNED BEFORE I WENT WEST WAS THAT WE WERE DONE, WE HAD ALL THE QUESTIONS LAID OUT, THEY WERE ESTABLISHED AND EVERY SESSION THERE WERE NEW QUESTIONS, NEW AREAS, NEW THINGS WE HADN'T APPRECIATED THAT WERE ON THE TABLE. I DON'T KNOW HOW LONG THIS OPERATION WORKED, IN THAT REGARD DLEES AT THE MOMENT IS WORKING WELL. WE SEND TRAINEES HERE AT NCI, IN AUGUST, AND EACH WORKSHOP AS I SAID CONTINUED TO ADD QUESTIONS, WE NOW HAVE A SERIES OF OTHER WORKSHOPS PLANNED WITHIN THE COMMUNITY, AND NCI, AN INTERNAL GROUP TRYING TO BUILD RECOGNITION OF THE PROGRAM HERE AND THEN I'M GOING ON THE ROAD AGAIN, WE'RE GOING TO TUSCON AND TO HOUSTON THE NEXT COUPLE OF MONTHS. PLEASE LOOK AT THOSE. AND IN EVERY CASE WE BEGAN TO ADD THOSE QUESTIONS. SO THAT BRINGS THIS TO THE RFA. YOU'RE BEGINNING TO DEVELOP OOH LANDSCAPE OF QUESTIONS TO PAINT THIS PICTURE, THE BOUNDARY BETWEEN KNOW AND WANT TO KNOW IN AREAS THAT WE THINK WE NEED TO EXPAND AND WORK ON THAT. AND SO EARLIER THIS YEAR, WE EXPANDED THIS EXPERIMENT TO MOVE FORWARD TO THINK HOW YOU USE THIS TO DRIVE RESEARCH PORTFOLIO DEVELOPMENT. SO AN RFA WAS BROUGHT FORWARD BUT INTERNALLY AS ONE DOES HERE AT NCI IS APPROVAL THROUGH THE BSA. BASED ON 24 PROVOCATIVE QUESTIONS THAT MET OUR CRITERIA. I'LL GIVEN YOU A SNIP PET OF IDEAS ABOUT A SERIES OF THOSE IN THE NEXT COUPLE OF SLIDES. THEY CRSES A BROAD RANGE OF COMMUNITY, I THINK WE TRIED TO TOUCH EVERY PART OF OUR WORLD. WE HAVEN'T GONE IN AS MUCH DEPTH AS WE MIGHT BUT YOU CAN SEE THE SETTINGS. IN EACH CASE WE DID A PORTFOLIO REVIEW TRYING TO IDENTIFY WHAT ALREADY WAS DONE OR WAS BEING WORKED ON NOW IN THE COMMUNITY OR ACTUALLY ACROSS ALL CANCER RESEARCH ORGANIZATIONS ACROSS THE WORLD. TO TRY TO MAKE SURE WE'RE WORKING IN AREAS THAT WERE NEW, IT CLOSES NEXT WEEK, THIS RFA, AND THERE'S A WHOLE REVIEW PROCESS PUT IN PLACE TO TRY AND MANAGE THIS OPERATION. PROVOCATIVE QUESTIONS KEEP RISING TO THIS LEVEL. WHAT WE'RE LOOKING FOR IN THESE SETTINGS IS AN OPPORTUNITY TO BROADEN OUR RESEARCH PORTFOLIO. I'M LOOKING AREAS WE'RE NOT PAYING AS MUCH ATTENTION AS WE WANT TO. MORE ABOUT THAT LATER. A QUESTION I'LL COME BACK AT THE VERY END IS IF THIS IS GOOD, IF THIS WORKS, DO WE REPEAT AND LOWRNLG SHOULD IT BE BE IN THAT SETTING. THERE'S A WEBSITE, WE PICKED UP QUESTIONS BOTH FROM WORKSHOP AS WELL AS THE COMMUNITY. EVERYBODY WAS INVITED TO JOIN THE WEBSITE, YOU JUST REGISTER YOUR QUESTIONS AND COMMENTS, QUESTIONS CAN GO IN. THERE ARE 150 QUESTIONS AND COMMENTS THAT CAME IN ON THE WEB. THIS WAS A VERY POPULAR SITE, 1800 HITS A DAY. PRETTY GOOD HIT, PARTICULARLY FOR THIS SORT OF OPERATION. SO HERE IS THE RFA BOTH R-21 AND RO-1s WE REALIZE THIS IS A NEW OPERATION, WE HAVE NEVER DONE IT BEFORE, WE TRY TO KEEP THE MECHANISM SIMPLE, SOMETHING EVERYBODY HAS EXPERIENCE WITH WITH TO RECOGNIZE AND KNOW HOW TO RESPOND. THE R-21 WAS STANDARD TWO YEARS, THE RO-1 WAS FOUR YEARS THINKING THIS WAS A PRELIMINARY OPERATION TO BUILD A NEW SETTING TRY TO MOVE INTO A NEW WORLD AND YOU OUGHT TO BE ABLE TO GET TO THAT STAGE TO SHOW THAT YOU HAD GOOD DATA TO ORGANIZE THE NEXT ROUND OF FUNDING SO A YEAR SHORTER THAN ONE MIGHT EXPECT IN AN RO-1. BUDGET 15 MILLION LOOKING FOR THAT SWEET SPOT, ENOUGH TO SHOW COMMITMENT FROM THE COMMUNITY, BUT NOT PUT ENOUGH -- SO MUCH MONEY INTO THE AREA THAT THAT IT WAS INAPPROPRIATE. THE REVIEW CRITERIA, SIMILAR FOR MANY PARTS OF THE -- HIGHLIGHT A COUPLE OF THINGS HERE, THESE ARE AREAS THAT WE THINK ARE IN NEW -- WHERE THERE'S NOT A LOT OF WORK BEING DONE SO IN MANY WAYS THE REVIEW PROCESS CONSENT TRAITS ON IDEAS AND STRENGTH OF PEOPLE'S IDEAS, NOT SO MUCH PRELIMINARY DATA BECAUSE IN MANY CASES THERE WON'T BE PRELIMINARY DATA IN OTHER >> MR. CASEY: S MAKING SURE IT'S NOT WEIGHTED BY THE STRENGTH OF PRINCIPLE INVESTIGATOR FOR THE STUDIES. AS WE SAY IT WILL CLOSE IN A SHORT WHILE AND WE'LL SEE HOW IT GOES. QIS WE GO THROUGH HERE, THIS ACTUALLY I FOUND TOUT THIS MORNING IS OUR MOST POPULAR QUESTION AS FAR AS THE APPLICATION THAT LEADS TO LETTERS OF INTENT PUT IN TO DATE WHICH WAS ACTUALLY PQ-1, HOW DOES OBESITY CONTRIBUTE TO CANCER. HERE, I WANT TO POINT OUT THAT THE OPERATION DOESN'T SAY TELL US MORE ABOUT HOW OBESITY IS LINKED TO CANCER, WHAT THE RISK FACTORS ARE. IT SAYS HOW DOES OBESITY CONTRIBUTE TO CANCER RISK. WE'RE ASKS MECHANISTICALLY AND THERE'S A SERIES OF PARAGRAPHS WITH THIS ON THE WEB, WHAT EVENTS OF OBESITY MAKE THAT CHANGE THAT ACTUALLY DRIVES THIS SETTING. SO MANY OF YOU ARE AWARE, THERE'S A CONNECTION BETWEEN OBESITY AND HIGHER RISK IN CANCER IS NOW WELL ESTABLISHED AND DEVELOPED IN A LOT OF VERY CAREFUL STUDIES. I HIGHLIGHT AN EXAMPLE HERE, A STUDY THAT LOOKS FIRST IN WOMEN, THE INCREASED RISK IN DIFFERENT TUMOR SITES N MEN THE SAME EXAMPLE, CERTAIN TISSUES ARE VERY SENSITIVE TO RISK FACTORS INVOLVED IN OBESITY. THIS EVENT IS SOMETHING THAT'S BEEN A REMARKABLE CHANGE IN THE AMERICAN POPULACE. HERE IS A INTERVIEW YOU HAVE SEEN THIS FROM RISK SURVEILLANCE SYSTEM LOOKING FROM 1990 TO 2009 ABOUT CHANGING OBESITY TRENDS AND THEN OBVIOUSLY HAS TRANSLATED INTO AN INCREASE IN PRESUMABLY A LONG TERM INCREASING RISK OF OBESITY. THE CANCER HAPPENS TO BE ONE OF THE DISEASES THAT'S MOST DRAMATICALLY AFFECTED ALMOST DOUBLING THE RISK IN THAT SETTING, BLOCKED BY SURGERY. ONE THING THAT I LIKE PARTICULARLY ABOUT THIS SUBJECT IS NOT ONLY WE TRY TAKE THIS OBESITY OBSERVATION, MOVE IT INTO MECHANISM BUT WE'RE ALSO TRYING TO JOIN THE FIELD OF RISK IDENTIFICATION AND CANCER BIOLOGY. SO FOR ME SOMEBODY WHO IS A BASIC BIOLOGIST WHO SPEND A LOT OF TIME OVER THE LAST YEAR TALKING WITH COLLEAGUES IN EPIDEMIOLOGY, I HAVE LEARNED TO HEAR THEIR LANGUAGE AND I HAVE LEARNED TO UNDERSTAND WHAT TASKS THEY USE THE IDENTIFY RISK. BUT ONE THING WE NEVER DID AND NEVER HAD THE OPPORTUNITY WAS TO EXPERIMENT TOGETHER. THIS QUESTION ASKS FOR THAT. HOW DO YOU MOVE THE OBSERVATION OF INCREASED BODY MASS IN THE CHANGES THAT ACTUALLY RELATE TO THE PROBLEMS THAT A BASIC BIOLOGIST THINKS ABOUT. SO WE'RE TRYING TO BUILD THIS BRIDGE THEN FROM THE OBESITY EVENT INTO EVENTS WE RECOGNIZE BEGINNING OF CANCER DEVELOPMENT. A SECOND EXAMPLE THIS RELATES TO THE ONES I SHOW YOU FROM THE LANSETT PAPER FAMILIAR WITH EARLY IN JANUARY OF THIS YEAR, THIS OBSERVATION LOOKING AT A SERIES OF META ANALYSIS OF CLINICAL OBSERVATIONS OF THE RELATIONSHIP OF LONG TERM ASPIRIN TREATMENT AN CANCER INCIDENCE. MAKING A RATHER DRAMATIC CHANGE IN THE OVERALL CANCER AND DEPENDING ON THE SITE, NAMING 30, 35% REDUCTION IN CANCER RISK. AND THE QUESTION WAS REALLY AGAIN DERIVE FROM THE THAT OBSERVATION BUT THINKING NOT ABOUT THE OBSERVATION OR REPEATING THE OBSERVATION OR PENDING AT THE DIFFERENT TUMOR SITES BUT WHAT WERE THOSE MECHANISMS INVOLVED HERE. WITH ASPIRIN, IT MAYBE ANTI-INFLAMMATORY BUT COULD BE FROM MY EVENT SO WHAT IS THAT CHARGE? WHAT IS THAT EVENT THAT ASPIRIN DRIVES IN THESE SETTINGS THAT MAKES US DIFFERENT? AGAIN, THIS IS A TISSUE-SPECIFIC EVENT. THERE ARE A NUMBER OF TISSUE SITES THAT ARE SENSITIVE TO THE INCIDENCE RATES AND ASPIRIN PEOPLE THAT TAKE ASPIRIN ROUTINELY. AL KANUSIN TAUGHT ME 15 SO I ROUTINELY TAKE MY ASPIRIN, I GOT MY FINGERS CROSSED BUT OTHER SITES HAVE NO CONNECTION AT ALL. SO AGAIN, THERE'S TISSUE-SPECIFIC EVENT, A MOLECULAR EVENT AND WHAT ARE THOSE EVENTS? CE FINE OUT WHAT'S TRUE HERE IS AN EXAMPLE OF ONE PART, WEST COAST TRIP IN SAN FRANCISCO. AND THIS WAS AN INTERESTING MOMENT FOR ME. AS A BASIC BIOLOGIST I THOUGHT ABOUT THE SELECTIVE PRESSURES THAT ARE ON A TUMOR AT EARLY STAGES AND WHAT'S INVOLVED THERE. I SAY WHAT ARE THE SELECT ACTIVE PRESSURES, WHAT'S IMPORTANT IN THOSE THING? WHAT CAN WE TELL ABOUT EARLY TUMORS. AN INDIVIDUAL THAT WAS PRESENT THERE WAS AN EVOLUTIONARY BIOLOGIST. HE SAY YOU'RE THINKING ABOUT TUMOR WITH WRONG IMPACT. SOMEBODY WHO THINKS ABOUT POPULATION DYNAMICS THINKS ABOUT TUMOR DEVELOPMENT IN THAT SETTING. THE EXAMPLE I PICKED UP HERE IS NOT FROM TUMORS, THIS IS FROM YOU PROBABLY REMEMBER THIS FROM YOUR HIGH SCHOOL OR COLLEGE BIOLOGY BOOK. THIS IS A PEPPER MOTH FROM ENGLAND. YOU'LL REMEMBER IN THE CHANGE IN DEVELOPMENT OF INDUSTRIAL REVOLUTION IN THE MID 1800S IN ENGLAND THE BIRCH TREE BARK WAS QUITE WHITE WHEN IT STARTED BUT QUITE DARK AFTER THE FACTORIES PRODUCE THE SMOKE THAT CORD IT. THE TREE BARK AND SURROUNDING FOR RESTS AROUND THE FOUNDRY. THE MOTH WAS ORIGINALLY WHITE, YOU CAN SEE IN THE TOP, VERY WELL DISGUISED. BUT AS THE TREE BARK BEGAN TO CHANGE A REMARKABLE THING HAPPENED. THIS MOTH, THE COLOR OF THIS MOTH WAS COMPLETELY SELECTED TO FOLLOW THE COLORATION AND HERE IS THAT MOTH SEVEN GENERATIONS LATE WE ARE A DARK COLOR, VERY WELL -- THIS HAPPENS TO BE A GENETIC SELECTION BUT IT'S VERY RAPID, EVOLUTION IN PROCESS AND REALLY POINTSES OUT RATHER DYNAMIC PROCESS SORKS THIS EVOLUTIONARY BIOLOGIST SAID I CAN TELL YOU BY PRINCIPLES IF YOU HAVE A CELL POPULATION THAT ISKINE MIC AND CAN CHANGE AND YOU HIT IT WITH A STRONG AGENT, SELECTED AGENT YOU WON'T AUTOMATICALLY FIND THOSE IN POPULATIONS. IF YOUR CELL POPULATION IS DYNAMIC BUT CAN'T CHANGE PERHAPS YOU CAN MAKE TREATMENT WORK LONG TERM BUT I DONE CARE WHAT YOUR AGENTS ARE, IF YOU HAVE THAT CELL POPULATION I KNOW THE LAWS FROM DARWINIAN LAWSES THE DARK MOTH COMES UP. WE TOOK THAT STATEMENT STRONGLY MADE AND THIS SETTING. WE BEGAN TO TALK A LITTLE BIT AND HE SAID WHAT I THINK YOU OUGHT TO BE LOOKING AT ARE METHODS THAT AREN'T SO STRONG IN THEIR SELECTION. THEY CAN BE ACTUALLY VERY DIRECTEDDED AND PARTICULAR AGAINST THE TUMOR YOU'RE AFTER BUT ALMOST ALL MUTATIONS ARE DELETERIOUS. THE FINANCE SURVIVAL IS REDUCED DRAMATICALLY HE PREDICTS VERY MUCH IN THAT SETTING SO IF YOU DON'T DRIVE THAT SELECTION THAT HARD YOU MIGHT BE ABLE TO GET A STATIC SITUATION WHICH THE TUMOR WOULD REMAIN COMPETITION GOING ON BETWEEN THE WILD TYPE CELLS AND THE CELLS THAT ARE UNDER THIS PRESSURE THAT DEVELOP MUTATIONS BECAUSE THEY DON'T GROW AS WELL. YOU OUGHT TO BE ABLE TO ESTABLISH A FOUNDATION TO GET A STABLE POPULATION OVER TIME. I STHOWGHT IT WAS A PROVOCATIVE THOUGHT BUT I WANT TO FIND OUT. I WANT TO KNOW. ONE QUESTION, NUMBER 21 ASKS THAT QUESTION. CAN WE TRY THAT? IT'S PROBABLY A MOUSE, PROBABLY ANOTHER MODEL. WE CAN SEE WHAT HAPPENS. BUT IT WAS A FUN DISCUSSION WITH SOMEBODY ELSE WHO THINKS ABOUT BIOLOGY FROM A DIFFERENT ANGLE. I DON'T THINK ABOUT OR HAVE THE SKILLS TO WORK ON THOSE. I'LL FINISH WITH ONE OTHER QUESTION. THIS WAS IN FACT THE QUESTION STARTED UP ALL OF OUR PRESENTATIONS, PROVOCATIVE QUESTIONS, IT'S HAROLD'S FAVORITE QUESTION IN THE SETTING EXAMPLE THAT HE GE GAN TO HELP US THINK ABOUT TO BEGIN TO THINK ABOUT WHAT A PROVOCATIVE QUESTION IS. THE QUESTION REALLY RELATES BACK TO LANCE ARMSTRONG AND TESTICULAR CANCER CURE THAT OCCUR FROM MEDICATIONS LIKE CISPLATIN. ANY OF YOU TREATED OR FAMILIAR WITH THAT TREATMENT IT GOES THROUGH, THERE ARE 85% CHANCE OF CURE IN THAT SETTING THE CURE IS DURABLE. WE HAVE A REAL CHANGE IN THAT SETTING. BUT FOR SOME REASON WE DON'T KNOW WHY, WHY SO PENETRANT IN THAT SETTING AN HAROLD START AD PROVOCATIVE DISCUSSION AND WE USE IT AS A COMMON THREAD THROUGHOUT, IF WE KNEW WHY, IF WE KNEW WHY THAT POPULATION OF CELLS WAS DYING IN THAT SETTING WE CAN USE AS A TREATMENT FOR WHAT OTHER TREATMENTS LOOK. SO THE QUESTION HERE IS AGAIN, WHY ARE THOSE CANCERS CURED. SO WHAT'S THE VALUE? HIGHLIGHTS NEW RESEARCH QUESTIONS THAT WE THINK NEED ATTENTION, IT ENGAGES THE COMMUNITY AND DISCUSSION I HAVE TO SAY IT HAHN A JOY TO BE INVOLVED WITH, THE DISCUSSIONS HAVE BEEN FUN TO THE POINT, NO KNOCK DOWN DRAG OUTS, NO BLOOD BUT LOTS OF GOOD INTELLECTUAL EXCHANGE ABOUT WHAT THE RIGHT QUESTIONS ARE. IT PUSHES THE NEW RESEARCH AREAS, I THINK THIS IS PARTICULARLY IMPORTANT AT THIS TIME. WE'RE TRYING TO CHANGE THE RESEARCH PORTFOLIO RATHER SIMPLE WAY HERE, MY THOUGHTS IN THIS REGARD IS THERE ARE 10 RESEARCH GRANTS IN THE HOTTEST AREA IN YOUR FIELD, IS THAT REALLY WHAT YOU WANT? WOULDN'T YOU RATHER HAVE FOUR IN THAT AREA OR FIVE AND SPREAD THE OTHER ONES INTO OTHER SUBJECTS UNTIL THEY ACTUALLY BALANCE OUT IN THIS SO YOU CAN TAKE THOSE SMART PEOPLE IN OTHER AREAS, THAT SEEMS LIKE A REASONABLE THING TO DO. SO WE'RE TALKING A POSSIBILITY OF A REASONABLE WAY OF REBALANCING THE PORTFOLIO. MONEY GETS TIGHT, WE ALL MOVE TO THE CENTER. WE ALL PICK EXACTLY WHAT SUBJECTS WE KNOW ARE THE HOTTEST ONES OR ARE THE BEST CHANCE OF GETTING FUNDED. GRANT WRITERS DO IT, WE ALL THINK COMMON LINE. YOU HEAR A STORY AND PICK IT UP AND RUN WITH IT. THIS SPREADS OUT THE OPERATION IN A SIMPLE WAY. WE'LL LOOK AT UNDERSTUDIED AREAS. WHAT'S EVALUATION FOR SUCCESS? THIS IS NOT SIMPLE. STIMULATE EXCITEMENT. WE OUGHT TO THINK ABOUT AT LEAST DO ANOTHER ROUND AS WE GO THROUGH. SO RARELY IN THAT SETTING, I HEARD THIS MORNING AS OF NOW 701 LETTERS OF INTENT. APPLICATIONS FOR 701 PREEP L, NOT MANDATORY SO WE MIGHT GET MORE, MIGHT GET LESS BUT OBVIOUSLY WE HIT A NERVE IN THE IMMUNITY, THAT'S RESPONDING WELL. THE WEBSITE HIGHLY POPULAR, 1800 HITS A DAY. SO I THINK IN THE FIRST LITTLE BIT WE KNOW WE'RE GENERATING SOME ATTENTION TO THIS SETTING. IT'S A TOUGH TIME, NOT SURPRISING PEOPLE TURN TO THIS BUT IT'S NOT SOMETHING PEOPLE RUN FROM SO THAT'S A GOOD FIRST ONE. INTERMEDIATE TERM SUCCESS IF WE WEREN'T DOING THIS RIGHT EACH APPLICANT AS THEY GO ON OUGHT TO MOVE IN THE GRANT POOL. THERE WERE A NEW AREA AND THEY HELPED BILL IT THEY WOULD BE IN A PERFECT PLACE TO WRITE AN RO-1. THESE ARE APPLICATIONS PEOPLE MOVE IN, MAKE THEIR STAB AND MOVE OUT INTO TO THE RO-1 SO THEY CAN COMPETE, R-21 THROUGH THAT SETTING. LONGER TERM WE'RE EXPECTING ANSWERS TO THESE QUESTIONS. THAT'S HELPFUL. WE'RE THINKING ABOUT GETTING A BETTER UNDERSTANDING, AND BASICALLY WE OTHER TALKING ABOUT IF YOU LOOK AT PORTFOLIO WITH PEAKS YOU SHOULD BEGIN TO GET SOME FILL IN THOSE AIR OTHER AREAS WHICH THE GRANTS TRYING TO AIM FOR IF WE'RE SUCCESSFUL. AND IF THAT IS SUCCESSFUL, IT RAISES REALLY INTERESTING QUESTION, ONE I'M FASCINATED WITH RIGHT NOW, JIM IS SITTING THERE SMILING, HE KNOWS THAT'S A SUBJECTS I LIKE TO THINK ABOUT. IF THIS WORKS, AND YOU CAN ACTUALLY PUT A LARGE PORTFOLIO IN FRONT OF THE COMMUNITY THEY'RE OF VALUE, HOW BIG A PROBLEM -- OPERATION SHOULD WE HAVE? SHOULD WE REPEAT ALL THE TIME, IT DOESN'T TAKE OVER THESE THINGS BUT YOU CAN IMAGINE A REASONABLE FRACTION OF YOUR PORTFOLIO MONEY SHOULD BE PUT INTO THIS OPERATION. ONE THAT SAYS IF IT DOES WORK WE HAVE BIGGER ISSUE WE HAVE TO THINK ABOUT HOW WE DO, HOW DO YOU MAKE IT WORK LONG TERM, HOW DO YOU GENERATE THE QUESTIONS. BEREFINE AND GET BETTER THINKING IF WE'RE SUCCESSFUL IN THAT AREA. THANKS, NOTICE POINT. MY COLLEAGUES IN THIS HAVE BEEN EARLY ON TYLER JACKS FROM MIT WAS PART OF OUR TEAM, OBVIOUS ENJOY WORKING WITH ALL THREE OF THOSE GUYS. BIG COORDINATION HELP FROM MAUREEN JOHNSON AND (INDISCERNIBLE) INVOLVED IN GOING EACH OF THESE WORKSHOPS OR A DOCUMENT BY NATION LISTENING TO ALL THESE THINGS TRYING TO TAKE NOTES AND PULLING THOSE THINGS THROUGH. WHO REALLY TOOK THIS ON AND TRIED TO FIGURE OUT HOW YOU DID A QUICK PORTFOLIO ANALYSIS. WE GAVE IN ONE CASE ABOUT 30 DAYS TO TURN OVER THAT QUESTION AND A SERIES OF TEN QUESTIONS WITH A FULL PORTFOLIO ANALYSIS. SO THEY HAVE DONE A GREAT JOB, AS WELL AS THE STAFF. THE WEBSITE WAS BUILT BY LISA AND CLINT AND THE CONCEPT REALLY NOW THE SETTINGS HAVE BEEN PASSED ON TO CHRIS JUAN ANDIERRY (INAUDIBLE) AND JERRY IS THE PROGRAM OFFICER TRYING TO PULL TOGETHER A MULTI-DIVISIONAL COMPONENTS. HOPE I'M OKAY ON TIME. HAPPY TO STOP THERE AN ANSWER QUESTIONS. >> THANK YOU THAT WAS GREAT. TIME FOR QUESTIONS. >> LET ME ASK THE PROVOCATIVE QUESTION ABOUT THE PROVOCATIVE QUESTIONS. WHETHER YOU'RE SURE YOU'RE STIMULATING RESEARCH IN NEW AREAS OR SIMPLY STIMULATING CLEVER RESEARCHERS TO RESHAPE THE WORK THEY WANT TO DO, ONE WAY TO ADDRESS THAT IS ANONYMOUS SURVEY WHEN IT'S DONE TO HAVE THAT VERY QUESTION. >> SO I THINK WE DO HAVE TO BE CAREFUL ABOUT THAT. YOU WON'T BE SURPRISED THAT EXPOST DOCS OF MINE CANGTD ME ALMOST IMMEDIATELY. COULD I RESHAPE MY RESEARCH TO FIT UNDER QUESTION NUMBER X? TO WHICH I SAID READ DETAILS ABOUT WHAT THE IS AFTER IN THAT SETTING. I THINK WE HAVE TO BE CAREFULFUL ABOUT THAT, WE HAVE TRIED TO MOVE INTO AREAS THAT ARE RELATIVELY UNPOPULATED WITH CURRENT RESEARCH PROPOSALS. THAT'S NOT COMPLETE. IN SOME CASES WE PICKED AREAS WHICH WE THOUGHT THEY WERE UNDERSTUDIED SO THERE'S A BALANCE THAT GOES ON IN THIS SETTING. I HOPE THE RESEARCH PROCESS IS PARTICULAR ENOUGH THEY WEED OUT GRANTS THAT DO EXACTLY WHAT YOU SAY. IF THEY AREN'T ON TOPIC IN THIS NEW AREA, I THINK THEY SHOULDN'T BE CONSIDERED UNLESS -- AND LET SOMEBODY ELSE WORRY ABOUT THAT. >> WHAT I SUGGEST AT THE END IS HAVE ANONYMOUS SURVEY AND ASK THAT QUESTION, FROM THE APPROXIMATELY CAN'TS. >> I THINK THAT'S AN IMPORTANT ASPECT. ENDORSING WHAT YOUR COMMENT WAS BUT THE PROCESS ITSELF WE ALSO NEED TO BE WARE. BUT WE ARE VERY CONSCIOUS, THAT PARTICULARLY IN TIGHT TIMES, THE RESPONSE MAYBE EVEN FROM ME, I HAVE TO ADMIT, WOULD HAVE BEEN, YOU KNOW, I'M GOING TO TURN MY GRANT IN F THEY TELL ME NO THEY TELL ME NO BUT I NEED MONEY BADLY ENOUGH THAT I WANT TO STIMULATE IT SO I THINK THERE'S GOING TO BE THAT NATURAL TENDENCY. I THINK IT'S CAREFUL TO BALANCE THAT. A SURVEY IS A GREAT WAY TO -- THERE'S OTHER WAYS TO MANAGE THAT SETTING BUT I THINK YOU TOUCH ON THE DIFFICULT NEXT STEP HOW DO WE GET REVIEW AND MANAGE THIS AND FIGURE OUT WHETHER WE'RE ACTUALLY DOING SOMETHING NEW. >> I WAS REALLY, REALLY PLEASED TO SEE THE QUESTIONS WHEN THEY CAME OUT BECAUSE AS A CLINICAL/TRANSLATIONAL RESEARCHER THERE'S REAL THINGS IN THERE FOR US. IT'S UNCOMMON, REALLY, THAT SOME OF THESE BIG INITIATIVES THAT ARE VERY SERIOUSLY SCIENCE-BASED REALLY HAVE A HOME FOR THE PEOPLE WHO LIKE TO DO CLINICAL AND TRANSLATIONAL RESEARCH SO IT WAS NICE TO SEE THAT COME OUT. THERE ARE ABOUT FIVE OR SIX OTHER QUESTIONS THAT HIT HOME WITH THE EXACT CLINICIANS AND TRANSLATIONAL PEOPLE NEED TO PARTICIPATE. THAT WAS REALLY NICE. >> THERE ARE NAYSAYERS OUT THERE, PEOPLE WHO READ THE LIST AND SAID I THOUGHT OF ALL THESE QUESTIONS BEFORE OR THIS ISN'T NEW. WE HAVE A BALANCE AND WE'RE MANAGING IT AND WE'LL GET BETTER AS WE GO ON. THEY'RE TIGHTENED UP IN THE WAY WE HAVE -- I THINK WE HAVE PEOPLE THAT ARE WE HAVE NCI STAFFERS WHO WILL STOP ME AND SAY IT DIDN'T DO A GOOD JOB AND I'M TRYING TO TAKE THAT TO HEART AS WE GO THROUGH. >> THANK YOU VERY MUCH. THAT WAS GREAT. >> I HAVE SO LITTLE CONTROL. I DON'T KNOW WHAT HAPPENED. >> SO WE'RE AT THE END. I'LL OPEN THE FLOOR UP TO ANY OTHER COMMENTS, ANY NEW BUSINESS. WE WILL BE WORKING ON AGENDA FOR THE NEXT MEETING. I ENCOURAGE PEOPLE TO PARTICIPATE IN AGENDA BUILDING SESSIONS, WE HAVE AT LEAST ONE IF NOT TWO. WE WILL TAKE TO HEART THE CONVERSATIONS WE HAD EARLIER ABOUT THE GLOBAL PORTFOLIO ANALYSIS THAT WAS DONE PREVIOUSLY HOW TO REPRESENT THAT AND GO FORWARD. I WOULD ALSO LIKE TO HAVE SOME THOUGHT AND SEE IF SOME AGREE ABOUT PERHAPS A PRESENTATION ON THE STATUS OF THE CTEP PHASE 1 UO-1 AN PHASE 2 NO 1 PROGRAM, PERHAPS NEXT MEETING OR THEREAFTER TRYING TO UNDERSTAND WHAT'S GOING ON THERE AS WELL. BUT IF PEOPLE HAVE OTHER AREAS THAT THEY WANT TO CONSIDER EITHER EMAIL SHEILA, MYSELF, OR IF YOU HAVE TIME, PARTICIPATE IN THE AGENDA BILLING SESSION, IT'S ACTUALLY VERY OPEN DISCUSSION OF ISSUES. SO SO IF PEOPLE HAVE CERTAIN TOPICS THEY WANT PRESENTED WE'RE MORE THAN HAPPY TO TRY TO FIGURE OUT THOUSAND DO THAT. SO IF THERE IF ARE NO OTHER COMMENTS I'LL MOVE FOR ADJOURNMENT. SO MOVED. WE'LL JUST HIT THE THING.