>> GOOD MORNING, EVERYBODY. WELCOME TORE THE NINDS COUNCIL, OUR 201st MEETING. IT'S GOING TO BE AN INTERESTING DAY. WE'RE LOOKING FORWARD TO EVERYONE'S INPUT ON TOUGH QUESTIONS. A COUPLE QUICK ANNOUNCEMENTS, OUR PENDING MEMBERS ARE JOINING US AS AD HOCS BECAUSE THE FINAL NOMINATION SLATE IS NOT YET APPROVED DOWNTOWN, WE'RE HOPING THIS WILL HAPPEN SOON. SO THANKS AGAIN TO EVERYONE FOR THEIR PATIENCE AND FOR COMING TODAY. I WANT TO ANNOUNCE TO THE GROUP, KAREN WAS NOT AWARE, PROBABLY A LOT OF PEOPLE AREN'T, THAT NINA SHORE HAS JOINED AS NINDS DEPUTY DIRECTOR. AND I AM SO EXCITED TO HAVE NINA HERE. SHE COMES WITH LOTS OF SCIENTIFIC EXPERIENCE, LOTS OF CHILD NEUROLOGY EXPERIENCE, AND LOTS OF ADMINISTRATIVE EXPERIENCE. AND I'M PLANNING ON GOING ON A LONG VACATION VERY SOON. SO NINA, SAY A COUPLE WORDS ABOUT YOUR HISTORY AND WHAT YOU HOPE TO DO HERE. >> IT'S A REAL PLEASURE TO BE HERE, AND A REAL PLEASURE TO BE AT MY FIRST COUNCIL MEETING. I KNOW MANY OF THE PEOPLE IN THE ROOM ALREADY FROM MY EXPERIENCE IN THE OUTSIDE WORLD, AS IT WERE. I REALLY COME WITH A LONG HISTORY OF JUXTAPOSING THINGS FROM VERY DIVERSE FIELDS AND WAYS OF APPROACHING NEUROSCIENCE. I HAVE DONE CLINICAL WORK AND HAVE SPENT MOST OF MY TIME IN THE RESEARCH LABORATORY IN A VERY, VERY BASIC PARADIGM, AND THEN FOR THE LAST 12 YEARS WAS CHAIR OF THE DEPARTMENT OF PEDIATRICS AT THE UNIVERSITY OF ROCHESTER ROCHESTER. I HOPE TO TAKE WHAT I LEARNED FUNDING MY RESEARCH AND BRING IT ME, LANDSCAPE ACROSS A NATIONAL PLATFORM. SO AGAIN, I'M VERY, VERY EXCITED FOR THE OPPORTUNITY TO BE HERE WITH YOU, AND LOOKING FORWARD TO THE MEETING. THANK YOU. IS. >> WHAT NINA FORGOT TO SAY, SHE WENT TO HIGH SCHOOL WITH MY SISTER WHO REMEMBERS HER VERY WELL FROM CARDOZA HIGH SCHOOL IN QUEENS, MANY DECADES AGO. OKAY. SO GOOD MORNING. IT'S VERY STRANGE TO BE SO CLOSE TO ALL OF YOU, WE'LL GET TO KNOW EACH OTHER TODAY. THE OTHER THINGS ARE THAT TIM COATSY COULDN'T COME IN PERSON. ARE YOU ON THE PHONE? >> GOOD MORNING, I'M HERE. >> REMEMBER TO VOTE WHEN WE GET INTO THE CLOSED SESSION OR EVEN IN THE OPEN SESSION. >> THANK YOU. >> OH, BY THE WAY, REMEMBER THAT THE AD HOC COUNCIL MEMBERS WHO ARE UNFORTUNATELY STILL AD HOC, YOU CAN SAY WHATEVER THE HECK YOU WANT BUT CAN'T FORMALLY VOTE. OKAY. AND WE'RE HOPING THAT THAT CHANGES SOON. JANET KEYSHUTTER IS COMING SOON. SHE GOT DELAYED. THAT TAKES CARE OF ALL THE COUNCIL MEMBER ATTENDANCE THINGS. WE'RE VIDEOCASTING, SO IF YOU HAVE TO FRESHEN UP, YOU CAN DO THAT DURING THE BREAK. MEETING IS OPEN TO THE PUBLIC UNTIL 2:00 WHEN WE GO TO CLOSED SESSION TO DISCUSS INDIVIDUAL GRANTS, I'LL MAKE MY USUAL REMARKS ARE CONFIDENTIALITY, CONFLICT OF INTEREST, ET CETERA. I'M GLOWING TO LAUNCH RIGHT IN. THE FOYERS THING WE NEED IS APPROVAL OF YOUR MINUTES, THE MINUTES FROM THE LAST MEETING WHICH WERE POSTED IN THE ECB, UNDER TAB 2. DOES ANYONE WANT TO DISCUSS THE MINUTES? IF NOT, I NEED A MOTION TO APPROVE. SECOND. ALL IN FAVOR. ALL OPPOSED. ANY ABSTENTIONS? I KNOW THE MINUTES CAN BE VERY CONTROVERSIAL. OKAY. THAT'S A SUCCESSFUL MOTION. THE OTHER THING IS THAT WE NEED TO REMIND YOU ABOUT THE DATES FOR THE FUTURE COUNCIL MEETINGS, UNDER TAB 1 OF YOUR NOTEBOOKS. TWO DATES IN 2019 HAVE CHANGED, SO CORRECT THEM IF YOU HAVE THEM ON YOUR CALENDARS. DEFINITELY ALWAYS LET KELLY KNOW AS FAR AS IN ADVANCE AS POSSIBLE IF YOU HAVE CONFLICTS WITH ANY OF THE MEETINGS. BY THE WAY, YOUR TERMS END ON JULY 3 1 OF THE YEAR, NOTED NEXT TO YOUR NAME WHEN YOU OFFICIALLY ROTATE OFF COUNCIL. OKAY. SO I'M JUST GOING THROUGH THE USUAL BOILERPLATE HERE. OH, ACTUALLY THIS IS SOMETHING WE DO ONCE A YEAR WHICH IS APPROVING THE COUNCIL OPERATING PROCEDURES. WE'RE REQUIRED BY LAW TO DO THAT. THEY ARE THE GROUND RULES THAT ESSENTIALLY EXPLAIN HOW WE CONDUCT COUNCIL. ONE OF THE THINGS THAT'S DESCRIBED IN THE DOCUMENT WHICH IS UNDER TAB 3 IN YOUR NOTEBOOKS IS THE THINGS THAT WE'RE ALLOWED TO DO WITHOUT COUNCIL APPROVAL. AND THERE'S NOT THAT MANY OF THEM BUT ONE OF THEM IS GIVING ADMINISTRATIVE SUPPLEMENTED UP TO $100,000, SO AS I SAID WE HAD POSTED THIS DOCUMENT FOR YOU TO SEE BEFORE THE MEETING. WE HAVEN'T PROPOSED ANY CHANGES THIS YEAR SO, AGAIN, UNLESS YOU WANT TO DISCUSS THE COUNCIL DELEGATED AUTHORITIES, WE NEED A MOTION TO APPROVE THEM. SECOND. ALL IN FAVOR. ALL OPPOSED. ABSTENTIONS. OKAY. NEXT I TALK ABOUT THE EXPEDITED REVIEW PROCESS WHICH I'M SUPPOSED TO REPORT ON EACH ROUND, THREE MEMBERS APPROVE GRANTS BEFORE THE MEETING OCCURS, THE IDEA BEING TO GET THE AWARDS OUT THE DOOR AS SOON AS POSSIBLE SO THE WORK CAN GET STARTED. THIS FOCUSES ON R01 WITH NO OUTSTANDING ISSUES, NOT CONTROVERSIAL, WE ROTATE AMONG THREE OF YOU, BEV, JANET AND DAVID THIS TIME, SO THANKS TO ALL OF YOU FOR DOING THAT. 77 APPLICATIONS WERE ELIGIBLE TO BE EXPEDITED THIS ROUND, OF THESE 37 HAVE ALREADY BEEN ISSUED, AND THIS AS I ALWAYS SAY IS A TESTIMONY, TESTAMENT OR TESTIMONY? A TESTIMONY TO OUR GRANTS MANAGEMENT BRANCH WHICH IS PHENOMENAL IN QUICKLY GETTING AWARDS OUT THE DOOR, HELDED BY TIA DECOSTA, ALL THE WAY IN THE BACK HERE. YOU CAN THANK TIA DURING THE BREAK IF YOU WANT FOR GETTING GRANT AWARDS OUT SO EFFECTIVELY. OKAY. NEXT I WANT TO INTRODUCE PEOPLE WHO RECENTLY JOINED NINDS WHO ARE LEAVING. I HAVE A WHOLE LITANY USUALLY, THERE HAVEN'T BEEN THAT MANY HIRES THIS YEAR SO I ONLY HAVE ONE INTRODUCTION. AND IT'S DOE KUMSA. DID I PRONOUNCE YOUR NAME RIGHT? SHE JOINED AS A CONTRACTOR, MOSTLY DOING IS SUPPORTING EFFORTS IN THE SPARK PROGRAM. I NEVER CAN REMEMBER WHAT SPARK ACRONYM STANDS FOR, DOUGH HER THESIS WAS ON THEORETICAL ASPECTS OF SELECTED ELECTRO CHEMICAL PROCESSES, MICROMACHINING, OMIC MICROSCOPY AND ELECTRO KATALYSIS, POSTDOCTORAL WORK AT CASE, SHE FOCUSED ON FINDING WAYS TO MAKE SURE ELECTRICAL STIMULATION FROM NEURAL DEVICES IS SAFE TO BE USED IN PATIENTS. CLINT, YOU HAVE SOMEBODY TO INTRODUCE? CLINT IS THE HEAD OF OUR DIVISION OF CLINICAL RESEARCH. >> YES, JEREMY IS NOT HERE. HE'S ON HIS WAY IN. BUT I CAN JUST ANNOUNCE I THINK SOME COUNCIL MEMBERS WERE HERE BACK FEBRUARY LAST YEAR WHEN I ANNOUNCED JEREMY BROWN WHO IS AN EMERGENCY MEDICINE PHYSICIAN AND HAD BEEN AT NIGMS RUNNING THE OFFICE OF EMERGENCY CARE RESEARCH BOTH HE AND THE OFFICE HAVE MOVED OVER TO NINDS WHICH WE'RE HAPPY ABOUT, JEREMY IS LEADING THE CHARGE ON OUR SIREN EMERGENCY CARE NETWORK, AND JEREMY IS NOW FULL TIME OFFICIALLY AT NINDS, WE'RE VERY HAPPY TO HAVE HIM HERE AND THE OFFICE HAS ALSO MOVED AND HE WILL SAY A COUPLE WORDS ABOUT THAT IF WE HAVE A CHANCE WHEN HE'S PRESENT. WE WANT TO WELCOME JEREMY. >> THANKS, CLINT. THE LAST -- WE HAVE A COUPLE MORE INTRODUCTIONS THAT OUR EXECUTIVE OFFICER MAUREEN GORMLY IS GOING TO DO. >> GOOD MORNING. I'LL BE INTRODUCING TWO NEW STAFF, WE WERE ABLE TO REPROGRAM FROM WITHIN NIH. IN THE BACK HILLARY SATILLA STARTED OCTOBER 2 AS NINDS ASSOCIATE DIRECTOR FOR WORK FORCE MANAGEMENT. , HAD PROVIDE SENIOR ADVISORY SUPPORT TO THE DIRECTOR AND SENIOR STAFF AS WE BUILD OUR CAPACITY FOR A REALLY HIGHLY ACCOUNTABILITY AND ENGAGED WORKFORCE, HAS WORKED WITHIN NIH WITH SCIENTIFIC AND CLINICAL LEADERS, SHE HOLDS A J.D. FROM AMERICAN UNIVERSITY AND MASTER'S FROM GEORGE WASHINGTON AS WELL AS CERTIFICATES AND SENIOR LEADERSHIP FROM GEORGETOWN, SENIOR PROFESSIONAL IN HUMAN RESOURCES. NEW STARTING OCTOBER 16 NOT HERE TODAY DENISE FORD WHO JOINED MANAGEMENT TEAM TO HELP US AS INTERNAL CONSULTANT WORKING TO FACILITATE IMPROVEMENT TEAMS AND IMPROVE THE EFFECTIVENESS ALL AROUND OF TEAM FUNCTIONING. SHE'S AN EXPERT IN STRATEGIC PLANNING AND ORGANIZATIONAL CHANGE AND SHE'S A RECENTLY RETIRED CAPTAIN FROM THE U.S. PUBLIC HEALTH SERVICE, SPENT HER CAREER AT THE NIH CLINICAL CENTER. THANKS. >> THANKS A LOT. ALSO I JUST LEARNED PAUL SCOTT, HEAD OF OUR OFFICE OF SCIENTIFIC POLICY AND PLANNING, HAS INTRODUCTIONS. >> I WANT TO INTRODUCE ANDREW HOOPER, OVER HERE, STAND UP. HE IS WORKING IN OUR OFFICE, OFFICE OF SCIENCE POLICY AND PLANNING. FELLOWSHIP IS ONE TO TWO YEAR PROGRAM THAT BRINGS SCIENTISTS TO D.C. TO LEARN ABOUT SCIENCE POLICY. HE B.A. IN PSYCHOLOGY FROM BOSTON UNIVERSITY 2005, THEN DID SOME TRANSLATIONAL RESEARCH IN RODENT MODELS OF HYPOXIA ISCHEMIA AT KENNEDY KRIEGER, ENLISTED IN ARMY, FIVE YEARS IN THE ARMY, SUPPORTING OPERATION ENDURING FREEDOM, AFTER THAT COMPLETED HIS DOCTORAL THESIS IN NEUROSCIENCE AT TUFTS IN 2016, FOCUSING ON GABAergic TRANSMISSION IN EPILEPSY. WILL BE, AN -- WELCOME, ANDREW. >> MORE ININTRODUCES. >> AMY ADAMS, HEAD OF OUR OFFICE OF SCIENTIFIC LIAISON. >> WE WERE ABLE TO RECRUIT AAAS FELLOWS IN LIGHT OF THE OVERALL HIRING FREEZE, I'M ALSO DELIGHTED TO INTRODUCE NINA SHUE AS A POLICY FELLOW, PRIOR TO THE FELLOWSHIP NINA COMPLETED NRSA FUNDED POSTDOCTORAL FELLOWSHIP UNIVERSITY OF MARYLAND COLLEGE PARK, RECEIVED Ph.D. IN NEUROSCIENCE FROM U PENN IN 2012, BACHELOR'S DEGREE FROM DUKE UNIVERSITY, FELLOWSHIPPED IN MY OFFICE, FOCUSED IN SCIENTIFIC COMMUNICATION AND OVERALL COORDINATION AND PLANNING FOR THE NIH BRAIN INITIATIVE. >> MEGAN MYERS, CHIEF OF STAFF FOR ME. >> GOOD MORNING. JACKIE WORD, STAND UP. SHE'S A AAAS FELLOW WORKING IN OFFICE OF THE DIRECTOR WITH ME AND WALTER, EARNED A Ph.D. IN BIOMEDICAL SCIENCE FROM THE UNIVERSITY OF CALIFORNIA SAN DIEGO, FALL 2016, LAB OF ALICE BATA, FOCUSING ON UNDERRING MITOCHONDRIA AND NEURODEGENERATION OF REPEAT DISEASES IN PATIENT DERIVED STEM CELL AND ANIMAL MODELS, BEFORE THAT MECHANISMS OF HISTONE METHYLATION IN YEAST IN THE LAB OF FRED WINSTON AT HARVARD UNIVERSITY, AND IDENTIFICATION OF NOVEL STRESS RECEPTORS AND FUNGAL PATHOGENS AT RHODES COLLEGE IN MEMPHIS, TENNESSEE. JACKIE IS WORKING ON A NUMBER OF HIGH PRIORITY PROJECTS INCLUDING HELPING SUPPORT TRANS-NIH ACTIVITIES RELATED TO PAIN AND OPIOID CRISIS. >> CLINT? >> YEAH, JEREMY BROWN IS HERE, WOULD YOU LIKE TO MAKE A COMMENT ABOUT THE OFFICE OF EMERGENCY CARE? >> VERY BRIEF COMMENT. >> I'M DELIGHTED TO SHOW YOU THE OFFICE HAS BEEN MOVED FROM NIGMS TO NINDS, FOCUSING ON EMERGENCY CARE RESEARCH, ANYTHING IN THE PRE-HOSPITAL SPACE AND EMERGENCY DEPARTMENT. I'VE GOT BIG SHOES TO FILL AS DIRECTOR BECAUSE THE FIRST ACTING DIRECTOR WAS WALTER, HE WAS REALLY INSTRUMENTAL IN GETTING THE OFFICE UP AND RUNNING WITH A TRANS-NIH FOCUS, WE REALLY GO OUT AND TRY AND GET OTHER INSTITUTES INVOLVED, AND AS WELL I'M A PROGRAM OFFICER WITHIN NINDS RUNNING THE SIREN PROGRAM. >> OKAY. THANKS, EVERYBODY. SO I THINK JUST TO MAKE THE STATEMENT RIGHT OFF THE BAT, NINDS IS BLESSED WITH GREAT STAFF, HIGH LEVEL OF EXPERIENCE, REALLY STRONG WORK ETHIC AND A REALLY DEVOTION TO THE INSTITUTE. AND SO WE'RE REALLY GRATEFUL TO ALL THE WORK THAT'S DONE AT COUNCIL. WE PRESENT WHAT PEOPLE HAVE BEEN WORKING ON FOR THE LAST FOUR MONTHS OR SO, AND BUT WE CERTAINLY VALUE YOUR INPUT BECAUSE IT IS VERY CLOSE SOCIETY HERE IN THE SENSE THAT WE CANNOT GET OFFICIAL ADVICE FROM ANYONE EXCEPT THE PEOPLE AROUND THIS TABLE AND WE VALUE YOUR INPUT. I'M GOING TO BRIEFLY TALK ABOUT SOME OF THE THINGS THAT HAVE HAPPENED SINCE THE LAST COUNCIL, AND GIVE YOU A GLIMPSE OF WHERE WE ARE AND START OFF FROM THE FINANCIAL BASIS, WHICH I GENERALLY DO. SO HERE YOU CAN SEE THE TOTAL NINDS BUDGET OVER THE YEARS. SO RECALL IT WAS VERY FLAT FROM 2004 TILL WE STARTED TO SEE THE FIRST INCREASE IN 2016. 2017 AGAIN A SIGNIFICANT INCREASE. AND BUT WE ARE IN OUR BUSINESS PUTTING OUT MONEY THAT'S GOING TO BE OBLIGATED USUALLY FOR THE NEXT FOUR OR FIVE YEARS, SO WE HAVE TO CONSIDER WHAT THE FUTURE IS GOING TO LOOK LIKE BUDGET-WISE WHEN WE DON'T KNOW WHAT THE FUTURE IS. SO THAT'S KIND OF THE GAME THAT WE'RE IN. NOW, I WOULD ALSO COMMENT THAT THE INCREASES THAT WERE SEEN IN 2016 AND 2017 FOR NINDS WERE VERY MUCH APPRECIATED BUT THEY ARE IN A SIGNIFICANT PART TARGETED, TARGETED TOWARDS TWO MAJOR AREAS, ONE IS BRAIN INITIATIVE, AN EXCITING PROJECT, AND THE OTHER IS MONEY THAT HAS REALLY ON THE NIA BUDGET BUT IS THEN USED TO FUND PROJECTS RUN OUT OF NINDS, ALZHEIMER'S RELATED PROJECTS, A LOT OF INCREASE IN THE BUDGET AT NIH AND WHERE THE BRAIN INITIATIVE CAME FROM. AS I MENTIONED, WE HAVE TO PLAN FOR THE FUTURE NOT KNOWING WHAT THE FUTURE IS, TO SIMPLIFY IT YOU CAN'T SPEND WHAT YOU DON'T HAVE. SO THAT MEANS YOU HAVE TO BASICALLY PLAN FOR THE WORST CASE FINANCIAL SCENARIO, BUT YOU HAVE TO ALSO HAVE THINGS READY SHOULD INCREASED FUNDING COME. THE GOOD NEWS, SINCE I'VE BEEN HERE AT NINDS, WE LEAVE A LOT OF GOOD SIGH SCIENCE ON THE TABLE AND FEEL SECURE SHOULD INCREASED FUNDING COME WE HAVE THINGS READY AND SCIENTISTS OUT THERE THAT WILL MAKE INCREDIBLY GOOD USE OF THAT FUNDING. SO WE KIND OF WORK ON THE WORST CASE AND BEST CASE SCENARIO BUT THINK THE BEST CASE SCENARIO IS SOMETHING THAT WE ARE COMFORTABLE DEALING WITH. WE ARE RESOURCE LIMITED IN WHAT WE DO. SO LOOKING TO THE FUTURE, WE HAVE THREE BUDGETS THAT ARE IN PLAY. WE HAVE THE PRESIDENT'S BUDGET, P B, A MAJOR CUT IN NINDS'S FUNDING. AND THEN WE HAVE THE HOUSE BUDGET, WHICH IS AN INCREASE OVER OUR 17 BUDGET, BUT NOT AS MUCH AS THE SENATE BUDGET. THOSE ARE THE THREE NUMBERS THAT ARE IN PLAY, AND WE HAVE TO PREPARE FOR ANY ONE OF THOSE. WE DO NOT HAVE A BUDGET NOW, AS PEOPLE PROBABLY KNOW READING THE PAPER, WE'RE UNDER A CONTINUING RESOLUTION, WHICH MEANS THAT THERE IS NO BUDGET AND YOU JUST CONTINUE WITH SAME APPROPRIATION YOU ARE LAST YEAR BUT IT'S ALWAYS FOR LIMITED AMOUNT OF TIME AND SO THE CONTINUING RESOLUTION RUNS OUT AGAIN ON FEBRUARY 9th. AS YOU KNOW, WE DID CLOSE OVER THE WEEKEND, AND FOR ONE -- BUT THEN CONGRESS CAME AND PUT THE CONTINUING RESOLUTION IN FOR A COUPLE WEEKS. WE'RE IN AN UNUSUAL SITUATION IN TERMS OF SPENDING. UNDER A COMPETING -- CONTINUING RESOLUTION, THE NON-COMPETING GRANTS, THESE ARE THE GRANTS AWARDED BEFORE, ARE THE -- THE MONEY GOES OUT BUT ONLY TO 90% OF WHAT WAS PLANNED. SHOULD THE BUDGET COME THROUGH AND IT'S A REASONABLE BUDGET, THEN WE WOULD FUND 100% F WE GOT A BIG BUDGET CUT WOULD PROBABLY NOT BE FUNDING NON-COMPETING TO 100% BUT WE'LL PROBABLY HAVE TO TAKE THAT 10% CUT AND CONTINUE IT. WE CONTINUE TO HAVE THIS CUT OF 17.5%, 12.5% FOR HISTORICAL REASONS, I'D LOVE TO GET RID OF THAT ONE OF THESE DAYS, BUT IT'S BEEN GOING ON FOR YEARS AND IT WOULD BE DIFFICULT TO ALL OF A SUDDEN CHANGE. AND I ALSO WANTED TO MENTION THAT THE BUDGETS GOING FORWARD HAVE FUNDING IN THEM FOR THE 21st -- FROM THE 21ST CENTURY CURES ACT, WHICH WAS PASSED AND FUNDS PARTICULAR PROJECTS GOING FORWARD, OF INTEREST TO US, IT FUNDS THE BRAIN INITIATIVE OUT TO 2026. AND SO THAT'S A BILL THAT'S PASSED THAT DIRECTS CONGRESS TO APPROPRIATE MONEY EVERY YEAR FOR THESE PARTICULAR PURPOSES AND THAT'S THE 21ST CENTURY CURES ACT. WHAT DOES THIS MEAN FOR US NOW? WHAT WE PAY A GREAT DEAL OF ATTENTION TO IS THE PAYLINE FOR OUR INVESTIGATOR-INITIATED GRANTS. AND FOR YEARS, WE WERE ABLE TO MAINTAIN A 14% PAYLINE, BUT RECENTLY THAT HAS NOT BEEN POSSIBLE ANY LONGER. SO IN 17, AS PEOPLE MAY KNOW, WE HAD TO DROP DOWN TO 12% PAYLINE, WE HAD THE INCREASE IN 16 WE WERE ABLE TO GO UP TO 15, BUT FOR MANY YEARS BEFORE THAT WE WERE AT 14. AND THE REASON IS THAT THE AMOUNT -- A COUPLE REASONS THAT WE'LL GO INTO THAT PLAYED INTO THIS PROBLEM WITH HAVING TO DECREASE THE PAYLINE. THE THING TO NOTE IS THAT THE PAYLINE IS NEW MONEY, SO IT DEPENDS ON THE AMOUNT OF COMPETING FUNDS THAT ARE AVAILABLE. SO THAT IS THE MONEY THAT YOU CAN PUT INTO NEW GRANTS EACH YEAR. SO OUR BUDGET IS ABOUT, YOU KNOW, $1.7 BILLION, BUT WE ONLY HAVE $355 MILLION COMPETING IN THAT YEAR FOR THIS PURPOSE. AND WHAT HAPPENED WAS THAT WE SAW ABOUT A 25% INCREASE IN THE APPLICATION RATE. SO REMEMBER WE KEPT OUR PAYLINE THE SAME, DESPITE THE GROWING NUMBER OF APPLICATIONS, AND SO THAT'S A SIGNIFICANT BUMP IN NUMBER OF APPLICATIONS WITHOUT ANY -- WITHOUT 25% INCREASE IN BUDGET AND TO COMPLICATE MATTERS MORE IN 17 WAS THIS PRETTY SIGNIFICANT JUMP IN THE AVERAGE COST OF A GRANT. SO THE AVERAGE COST OF A GRANT HAS BEEN BUMPING 400K, 370, 380, BUT THIS TIME UP TO 476K. THIS HAPPENED ACROSS NIH, WASN'T JUST US. THE FACT WE HAD INCREASED NUMBER OF APPLICATIONS, INCREASE COURSE FOR GRANTS IS WHAT FORCED US TO GO TO THE 12% PAYLINE. OKAY. AND WHAT THAT HAS DONE TO OUR SUCCESS RATE, THE SUCCESS RATE IS A LITTLE DIFFERENT THAN THE PAYLINE, IT'S ALL THE GRANTS THAT COME IN, YOU KNOW, THAT'S YOUR DENOMINATOR, WHAT PERCENT GET FUNDED, THAT'S YOUR NUMERATOR, AND SO OUR SUCCESS RATE WENT DOWN TO 17.7%, WHICH IS THE LOWEST IT'S BEEN IN A LONG TIME. AND ALSO IT'S NOT GOOD IN COMPARISON TO OTHER INSTITUTES. THESE ARE THE OTHER NEUROSCIENCE INSTITUTES, NICHD HAND UNDER STRONG STRESS FOR A NUMBER OF YEARS AND THEY ARE DOWN BELOW US, NIMH AGAIN IS HIGHER THAN US. SO THIS IS SOMETHING WE'D LIKE TO TURN AROUND BUT WE GOT INTO THIS PRIMARILY BECAUSE THE NUMBER OF APPLICATIONS AND MORE MONEY GOING INTO THE NON-COMPETING OBLIGATED POOL. NOW, THAT MONEY WILL RETURN AND RECYCLE BACK. REMEMBER THE AVERAGE GRANT IS FOUR YEARS OR SO, SO YOU START TO SEE THE MONEY FROM FOUR YEARS AGO THAT YOU PUT IN. SO I THINK WE'LL GET TO A BETTER STREAM BUT WE REALLY DO I THINK THE SCIENCE THAT'S COMING TO NINDS, THE NUMBER OF APPLICATION INCREASE, REALLY MEANS THAT WE NEED -- WE REALLY COULD USE GREATER RESOURCES TO ACHIEVE WHAT WE WANT TO ACHIEVE. SO LET ME STOP THERE AND ASK IF THERE ARE ANY QUESTIONS ON THE BUDGET BEFORE I TURN TO THE NEXT TOPIC. YES, BRUCE. >> WALTER, TWO QUESTIONS. ONE, HAS THERE BEEN CORRESPONDING INCREASE IN APPLICATIONS TO OTHER INSTITUTES AS WELL? AND THEN TWO, IS THERE ANY SENSE OF THE QUALITY OR STRENGTH OF INCREASED APPLICATIONS OVERALL COMPARED TO PRECEDING YEARS? > WELL, I THINK, YOU KNOW, MAYBE BOB COULD COMMENT. I THINK THE STRENGTH OF THE APPLICATIONS IF ANYTHING THEY LONG STRONGER EVERY YEAR, SO I DON'T THINK THAT IS AN ISSUE. IN TERMS OF APPLICATION FOR THE OTHER INSTITUTES, THERE WAS ACROSS THE BOARD AT NIH AN INCREASE IN APPLICATIONS BUT I DON'T THINK AT THIS LEVEL. NOW, WHAT HAPPENED THE OTHER THING THAT HAPPENED WAS YOU REMEMBER DURING THIS TIME PERIOD THERE WAS A SWITCH FROM THE FACT THAT YOU COULD SUBMIT A REAPPLICATION, AND THEN COULDN'T SUBMIT ANYMORE, THAT WAS TAKEN AWAY SO THAT ALSO LED TO A BUMP OF APPLICATIONS. IF YOU HAVE AN APPLICATION THAT DIDN'T GET FUNDED AND IT'S FREE, YOU HIT A BUTTON, IT GETS SUBMITTED, WHY NOT. SO I THINK THAT'S ALSO PLAYED INTO THE INCREASED NUMBER OF APPLICATIONS WHICH THEN AFFECTS THE PAYLINE. THE OTHER THING, THE R35, WE'VE TAKEN PEOPLE OUT OF THE R01 POOL WHO ARE STRONGLY COMPETITIVE R01 APPLICANTS AND THEY ARE NOT COMPETING ANYMORE. THEY ARE IN THIS R35 POOL. THAT ACCOUNTS FOR ABOUT A 1 TO 1 1/2% TILE POINTS, WE'LL GET TO THAT. NEXT TOPIC IS THE ISSUE WE'VE BEEN WRESTLING WITH HERE AND NIH, THE AGE DISTRIBUTION OF THE WORKFORCE, THIS IS A GRAPH THAT NIH SHOWS MANY TIMES, WHAT IT SHOWS IS THAT THE NUMBER OF FOLKS OVER 60 ARE TAKING A GREATER CHUNK OF THE NIH RESEARCH BUDGET. THE CHUNK GOING TO PEOPLE LESS THAN 45 YEARS OLD IS DROPPING, MAYBE PLATEAUING, AND THE PEOPLE IN THE MID-RANGE ARE ALSO DROPPING. AND SO THIS IS -- IT'S VERY HARD TO SAY WHAT IS THE RIGHT PROPORTION BUT I THINK MOST PEOPLE FEEL THAT THIS IS CRAZY, THAT THE TIME TO BECOME INDEPENDENT IF IT GETS INTO YOUR 40s IT REALLY TURNS PEOPLE, REALLY GOOD PEOPLE, AWAY FROM SCIENCE. AND THEY LOOK AT A CAREER WHERE THEY ARE POSTDOCS FOR SEVEN YEARS AND THEY MAY OR MAY NOT GET A JOB, SO WE REALLY THINK THIS IS A PROBLEM. AND I THINK THAT THAT IS -- THERE'S GENERAL CONSENSUS AROUND THAT. WHAT THE ACTUAL MIX SHOULD BE, I DON'T KNOW ANYBODY KNOWS. THE METRIC IS HARD TO DETERMINE WHAT IT IS. SO I WANT TO SAY ONE THING IS THAT IN MAY WE'LL PRESENT DATA FROM NINDS WITH REGARD TO THIS. I HATE TO TAKE CHRISTINE'S THUNDER BUT IT LOOKS LIKE THIS. WE'RE NO BETTER. I THOUGHT WE WOULD BE BETTER BECAUSE I THOUGHT NEUROSCIENCE WAS A YOUNG FIELD, AND ALSO BECAUSE NINDS HAS BEEN FUNDING EARLY STAGE INVESTIGATORS 10% HIGHER THAN A REGULAR PAYLINE NOW FOR 7 OR 8 YEARS. I THOUGHT THAT WOULD DRIVE THE AGE DOWN. BUT IT HAS NOT DRIVEN THE AGE DOWN. SO WE HAVE SOME REALLY HARD THINKING TO DO AND THAT WILL BE A MAJOR TOPIC FOR THE MAY COUNCIL. BUT FOR NOW, LET'S TALK ABOUT WHAT NIH DID. THEY RELEASED THE POLICY IN AUGUST. THEY GAVE IC SOME FLEXIBILITY AND IMPLEMENTATION BECAUSE IT WAS SO LATE IN THE YEAR, BUT THEY ASKED THAT EVERYBODY FUND EARLY STAGE INVESTIGATORS WHICH ARE PEOPLE TEN YEARS FROM TERMINAL DEGREE OR TERMINAL TRAINING. CLINICAL TRAINING, TO THE 25th PERCENTILE. THEY ALSO ASKED THAT THEY FUND PEOPLE WHO ARE WHAT'S CALLED EARLY ESTABLISHED INVESTIGATORS, THOSE ARE PEOPLE WHO WERE REALLY EARLY STAGE INVESTIGATORS AT ONE POINT, GOT THEIR R01 AND NOW ARE WITHIN TEN YEARS OF THAT INITIAL R01. AND THERE HAS BEEN CONSIDERABLE DISCUSSION ABOUT THIS, AND WE'LL TALK ABOUT THAT WHAT WE DID AND WHAT NIH IS DOING. OKAY. SO THEY ASKED, THIS IS THE ADVISORY COMMITTEE TO DIRECTOR, WORK GROUP ON NEXT GENERATION RESEARCH, ASKED THE INSTITUTES TO FOCUS ON PROGRAMS OF RESEARCH, PI ACCOMPLISHMENTS, RATHER THAN PROJECTS PER SE. THIS IS REALLY TO KIND OF ALLOW DIRECTION CHANGE IN THE MIDST OF EXECUTION OF PROJECTS. THEY ASKED US TO PRIORITIZE PROJECT TO FILL A CRITICAL KNOWLEDGE GAP AND REALLY THE CRITICAL ISSUES ARE THESE, EMPLOY SELECTIVE PAY, ABOVE THE PAYLINE FOR EARLY STAGE INVESTIGATORS. WE'VE BEEN DOING THAT FOR MANY YEARS TO MAKE GREATER USE OF BRIDGE AWARDS, WE'VE DONE THIS IN THE LAST COUPLE YEARS. ONE, WE HAVE FOLKS WHO LOOKS LIKE THEY HAVE -- THIS IS THEIR ONLY GRANT. IF THEY DIDN'T HIT THE PAYLINE, WERE WORRIED THEY WOULD LOSE THEIR LABS AND HAVE TO SHUT DOWN, WE GIVE BRIDGE AWARDS, ALLOW THEM TO APPLY AGAIN. MANY DO QUITE WELL, WE'LL TRY TO GET DATA WHEN THEY COME BACK FOR REAPPLICATION BUT THE OTHER REASON FOR THIS AS I MENTIONED FINANCIALLY IF WE FUND A GRANT WE'RE COMMITTING MORE OUT YEAR COSTS AND HAVE A PROBLEM WITH OUT-YEAR COSTS. IF WE BRIDGE PEOPLE IT'S ONE-YEAR MONEY, DON'T INCUR OUT-YEAR COURSES BALANCING OUR BOOKS INTO THE FUTURE. THE OTHER THING THEY ASK FOR IS LONGER PERIODS OF SUPPORT, R35 IS DOING THIS. AND SEPARATE REVIEWS FOR ESTABLISHED AND EARLY STAGE INVESTIGATORS, THEY HAVEN'T REALLY DONE THAT BUT THEY HAVE KIND OF MADE SOME ADJUSTMENTS AT CSR TO LOOK AT THE EARLY STAGE FOLKS BEFORE OR AFTER, I CAN'T REMEMBER LATEST. YES, AMY? >> A QUICK QUESTION ON THE POINT ABOUT THE LONGER PERIODS OF SUPPORT. MY MEMORY OF OUR R35 FUNDING IS THAT IT REALLY DIDN'T GO TO EARLY STAGE INVESTIGATORS OR EVEN EARLY ESTABLISHED INVESTIGATORS, THOSE WERE MORE VERY SENIOR INVESTIGATORS,& PROBABLY PART OF THE GROUP THAT WAS THAT GREATER THAN 60. >> WE CAN LOOK. I THINK WE DECIDED WHEN WE WERE GOING TO DO THIS THAT WE WEREN'T GOING TO ALLOW THAT TO BASICALLY TAKE OVER. I THINK IT'S ABOUT 30% ARE EARLY STAGE, WITHIN TEN YEARS OF FIRST R01. >> WE DID DECIDE NOT TO COMMIT TO EIGHT YEARS OF SUPPORT. AS LONG AS YOU HAD ONE CYCLE, YOU'RE ELIGIBLE FOR R35. THE LAST ROUND THERE WERE VERY FEW EARLY STAGE PEOPLE, AND THAT IS SOMETHING -- IN FACT WE'RE JUST CONSIDERING WHETHER TO DO ANOTHER ROUND OF THE R35, I WAS JUST TALKING TO MY DEPUTY ABOUT EXACTLY THAT ISSUE, WHETHER WE COULD HAVE A WAY OF ENSURING THAT MORE EARLIER CAREER INVESTIGATORS ARE PART OF THE PROGRAM. >> WE THOUGHT ABOUT TWO FOAS. YOU'RE RIGHT, WE DON'T WANT TO GET CAUGHT INTO THAT. >> (INAUDIBLE) HAS THAT BEEN LOOKED AT? >> I DON'T KNOW THE ANSWER. I CAN TELL YOU A COUPLE THINGS ABOUT THE BRAIN. IT HAS A LARGE PROPORTION OF NEW INVESTIGATORS, PEOPLE NEW TO NIH, AND I THINK ABOUT 40% OF THOSE ARE EARLY STAGE INVESTIGATORS. SO THE ONE THING THAT'S HAPPENING WITH BRAIN IS THAT, WHICH IS INTERESTING, THE PEOPLE WHO ARE APPLYING HAVE THESE NEW TECHNIQUES, WHO TEND TO BE THE YOUNGER PEOPLE. >> ALSO TEND TO BE GROUP GRANTS OR NOT? >> NO, THE YOUNGER PEOPLE ARE NOT USUALLY IN THE GROUP GRANTS. I THINK THEY ARE IN THEIR INDIVIDUAL GRANTS. YEAH, THE BRAIN INITIATIVE DOES LOOK YOUNGER THAN AVERAGE. >> I WONDER IF THERE ARE ANY LESSONS THERE. >> YES, GOOD POINT. THE LESSON IS OLD PEOPLE CAN'T LEARN NEW TECHNIQUES AND CAN'T APPLY >> I WANT TO WRAP MY MIND AROUND THE DENOMINATOR FOR AGE DISTRIBUTION. ARE THE NUMBER OF GRANTS BY AGE DIFFERENT FOR OLDER MORE ESTABLISHED INVESTIGATORS THAN JUNIOR SO WE SHOULD BE LOOKING AT THE SUCCESS RATE PER AGE GROUP, NOT THE PERCENT OF INDIVIDUALS WHO ARE FUNDED, WHEN THE DENOMINATOR IS EVERYBODY. YOU SHOULD BE -- IF THERE ARE MORE SENIOR INVESTIGATORS SUBMITTING GRANTS, THEN EXCUSE IT. >> OKAY. I'M NOT SURE I KNOW THE EXACT -- I DO KNOW IF YOU LOOK AT SUCCESS RATES, VERSUS AGE, THEY GET BETTER AND BETTER AND BETTER. BUT THAT MEANS THAT -- BUT THAT'S KIND OF A NO-BRAINER BECAUSE IF YOU STAY IN THE GAME LONGER YOU'RE GOOD AT WRITING GRANTS. SO SUCCESS RATE IS HIGHER FOR MORE EXPERIENCED FOLKS. >> DATA FROM THE CURVES, NHLBI DID AN ANALYSIS, THAT WAS DOLLARS, POINT WELL TAKEN. NOW, WE -- THERE'S AN NIH MANDATE THAT EVERY INSTITUTE HAS TO AT LEAST EQUALIZE THE SUCCESS RATE OF A NEW INVESTIGATORS APPLYING FOR FIRST R01 WITH SUCCESS RATE OF ESTABLISHED INVESTIGATOR APPLYING FOR NEW R01 SO WE'VE BEEN OVERSHOOTING PAY LINE FOR ESI, SO OUR SUCCESS RATE FOR ESI IS HIGHER THAN THAT OF ESTABLISHED INVESTIGATORS. ONE OTHER THING, SUCCESS RATE, YOU HAVE TO UNDERSTAND WHAT SUCCESS RATE MEANS. IF YOU SUBMIT AN APPLICATION TWICE INNING IN A YEAR AND ALSO FUNDED THAT'S ONE APPLICATION. THE ACTUAL RATE, AWARD RATE I BELIEVE, WHERE YOU TAKE THE NUMBER OF AWARDS YOU GET, DIVIDED BY THE TOTAL NUMBER OF APPLICATIONS IS ACTUALLY LOWER. YOUR CHANCES WHEN YOU SUBMIT AN APPLICATION OF GETTING IT ARE ACTUALLY LOWER THAN THE SUCCESS RATE, IF YOU UNDERSTAND WHAT I'M SAYING. >> OKAY. NED, DID YOU WANT TO SAY SOMETHING ABOUT EARLY STAGE AND BRAIN? >> NOTHING SERIOUS. JUST THAT WE IN TERMS OF THE BRAIN INITIATIVE DO HAVE NUMBERS. THE EARLY STAGE INVESTIGATORS IS AROUND 18% OF THE AWARDED GRANTS, PRETTY HIGH. WE HAVE ANOTHER POOL OF NEW INVESTIGATORS, SO THE TOTAL POOL OF NEW AND EARLY STAGE INVESTIGATORS IS AROUND 40%, WHICH IS REALLY QUITE HIGH. BECAUSE WE HAVE A LOT OF PEOPLE WHO ARE COMING IN AS FIRST-TIME NIH APPLICANTS, BECAUSE THEY ARE FROM FIELDS OUTSIDE OF TRADITIONAL NIH BIOMEDICAL FUNDING. WE DON'T HAVE INFORMATION ON, YOU KNOW, THE RELATIVE PROPORTION OF NEW INVESTIGATORS WHO ARE COMING IN AS CO-INVESTIGATORS ON MULTI-P.I. GRANTS. WE HAVEN'T COLLECTED THAT. WE HAVE COLLECTED THAT INFORMATION BUT WE HAVE NOT ANALYZED IT YET. >> OKAY. LET'S GO ON. SO THIS SLIDE BASICALLY SHOWS YOU THE FUNDING FOR EARLY STAGE INVESTIGATORS AT THE DIFFERENT PERCENTILES, WE FUNDED EVERYBODY TO 25th PERCENTILE. IN TERMS OF BRIDGE FUNDING, SO WE GAVE OUT 64 BRIDGE FUNDS, AND 43 OF THOSE WERE TO PEOPLE WHO WERE NOT EARLY ESTABLISHED INVESTIGATORS, OUR POLICY HAS BEEN NOT TO JUST USE BRIDGES FOR EARLY ESTABLISHED INVESTIGATORS BUT LOOK AT THE POOL IN GENERAL, AND TO FIND PEOPLE WHO WE THINK REALLY NEED A BRIDGE, SO THEY CAN COME IN WITH ANOTHER GRANT AND KEEP THINGS GOING. AND OF INTEREST, NIH HAS ALSO LOOKED AT THIS EARLY ESTABLISHED INVESTIGATOR POOL AND REALIZED IT DOESN'T MAKE A LOT OF SENSE TO PUT EXCESS FUNDING ON THAT GROUP BECAUSE IT BASICALLY TAKES MONEY AWAY FROM SOMEONE ELSE THAT'S VULNERABLE. SO THEY ARE COMING ALONG I THINK TO THE POLICY THAT WE'VE BEEN USING FOR A WHILE. AND THEN AS I MENTIONED WE ALSO AWARDED 37 R35s, AND THIS IS EIGHT YEARS OF FUNDING SO THIS IS THAT SPECIAL PROGRAM WHICH IS OUTLINED HERE, AND THE IDEA IS FROM MY POINT OF VIEW THIS IS TO ALLOW PEOPLE TO DO MUCH MORE INNOVATIVE RESEARCH, TO HAVE EIGHT YEARS OF STABLE FUNDING, SO THEY DON'T HAVE TO GO QUICKLY FROM ONE FLASHY DISCOVERY TO ANOTHER FLASHY DISCOVERY TO GET ANOTHER GRANT BUT DO A BODY OF WORK THAT STICKS AND ALSO HAVE MORE TIME TO REALLY BE IN THE LAB WITH THE DATA, MAKING SURE THAT THE DATA COMING OUT IS MORE RIGOROUS AND THAT TRAINEES IN THE LAB ARE BETTER MENTORED. AND THAT'S REALLY THINK THE VALUE OF THE R35. AND SO IT REQUIRES AT LEAST A 50% EFFORT, AND YOU CAN'T HAVE -- YOU'RE NOT GOING TO BE ABLE TO GET ANOTHER NINDS GRANT BUT COULD USE 50% EFFORT FOR AGING OR OTHER INSTITUTE GRANTS. IN THE FIRST YEAR 196 APPLICATIONS, 30 AWARDS, $25 MILLION SHIFT FROM THE R01 POOL INTO THE R35 POOL, IN YEAR TWO A MAJOR DROP IN THE NUMBER OF APPLICATIONS. WE'RE NOT CLEAR WHY THAT IS. IT MAY BE THAT, WELL, IT WAS A VERY HIGH LEVEL GROUP THAT GOT AWARDED AND PEOPLE MAY HAVE KIND OF SELF SELECTED OUT, SO 7 MILLION THAT WENT IN, IN 18, BUT I THINK WE WANT TO CONTINUE THIS PROGRAM AND PICK PEOPLE AGAIN WHO HAVE -- YOU CAN REALLY BANK ON THAT WITH THE FUNDING THEY ARE GOING TO DO REALLY GREAT THINGS OVER THE NEXT 8 YEARS. SO IT'S A LITTLE BIT CONSERVATIVE FOR US, IT'S NOT -- IT TAKES MONEY OUT OF THE R01 POOL, IT IS PEOPLE WHO WOULD PROBABLY BE GETTING R01s IN THE USUAL SITUATION, SO IT'S BUDGET SHIFTING BUT BUDGET NEUTRAL OVERALL. OKAY. THE NEXT THING WHICH I THINK WE JUST WANT TO MENTION, WE TALKED ABOUT THIS BEFORE, IS THAT NIH HAS REDEFINED CLASSIFICATION OF RESEARCH THEY CALL CLINICAL TRIALS. SO IT'S NOT THE OLD DEFINITION OF CLINICAL TRIALS, INTUITIVE DEFINITION. IT'S SOMETHING DIFFERENT. ANYTHING THAT INVOLVES HUMAN SUBJECTS, ANYTHING THAT PER PERSPECTIVELY ASSIGNS, SO A LOT OF PSYCHOLOGY EXPERIMENTS WOULD DO THESE THINGS. IN THE PAST WE'RE UNDERSTANDING HOW THE BRAIN WORKS, JUST A MECHANISTIC STUDY, NOT REALLY AFFECTING WHAT TREATMENT PEOPLE SHOULD TAKE SO BUT IN FACT NIH IS NOW DEFINING PRETTY MUCH ALL OF THESE BIOLOGICAL OUTCOMES AS HEALTH-RELATED OUTCOMES, BECAUSE WHY WOULD NIH BE DOING ANYTHING THAT DIDN'T HAVE A HEALTH-RELATED BIOMEDICAL OUTCOME? SO THE POOL OF RESEARCH THAT FITS UNDER THIS CLINICAL TRIAL MENTIONED BEFORE, THE DRIVING FORCE FOR THIS WAS TO HAVE -- TO GET THESE DATA FROM THESE -- THIS KIND OF RESEARCH MADE PUBLIC IN clinicaltrials.gov. SO ALL THIS WORK NOW HAS TO BE REPORTED IN clinicaltrials.gov, INCLUDING THE RESULTS. AND THAT'S THE BENEFIT OF THIS. THEN THERE'S A LOT OF BUREAUCRACY THAT GOES ON TO MAKE THAT HAPPEN NOW THE MEAT OF THE ISSUE IT WILL TAKE TIME TO GET USED TO THIS BUT THERE ARE NOW ALL THE GRANTS THAT NIH PUTS OUT, FOAS ARE NOW CLASSIFIED. THEY ARE CLASSIFIED AS EITHER A CLINICAL TRIAL IS NOT ALLOWED, HERE IS AN EXAMPLE, SO FROM THE BRAIN INITIATIVE A TARGETED BRAIN CIRCUITS PROJECT, SO THIS IS GOING TO BE ANIMAL EXPERIMENTS ONLY, CLINICAL TRIALS, THEREFORE NOT ALLOWED. HERE'S ANOTHER ONE NEXT GENERATION INVASIVE DEVICES RECORDING AND MODULATION OF HUMAN NERVOUS SYSTEM, THESE WILL BE DEVICES THAT GO INTO PEOPLE, THEY ONLY GO IN BECAUSE THEY HAVE SOME DISEASE. THEY MAY HAVE NOTHING TO DO WITH MODULATING THE DISEASE. SO THEY MAY BE EPILEPSY PATIENTS WHO ARE RECORDED AND THEN YOU TASK AND RECORD FROM THE NEURONS AS THEY DO SPEECH OR MEMORY, BUT THAT IS NOW CLINICAL TRIAL. SO IN THIS GRANT THIS IS CLINICAL TRIAL REQUIRED, EVERYTHING IS GOING TO HAVE PAPERWORK FOR CLINICAL TRIAL. THERE ARE OTHER FOAS WHERE IT'S NOT REALLY CLEAR WHICH WAY THINGS ARE GOING. IT WILL SAY CLINICAL TRIALS OPTIONAL. WE'RE TRYING TO PUT ON THE THE SUITE OF GRANTS SO NO ONE'S RESEARCH DOESN'T FIT SOMEWHERE BUT JUST TAKES A LITTLE TIME AND EFFORT TO TRY AND FIGURE OUT WHERE YOUR RESEARCH SHOULD GO. PROGRAM DIRECTORS AND THERE'S A GROUP AT OER THAT WILL ANSWER QUESTIONS ABOUT THAT. SOME OF THESE CLINICAL TRIALS HAVE ANOTHER CUT POINT IN THEM. TRYING TO UNDERSTAND LANGUAGE FUNCTION RECORDING FROM EPILEPSY PATIENTS WOULD BE A MECHANISTIC TRIAL, UNDERSTANDING MECHANISMS, SO THAT'S ANOTHER SUBDIVISION OF THE CLINICAL TRIAL. SOME OF THESE WILL SAY MECHANISTIC CLINICAL TRIALS ONLY. SO COMPLICATED, TIME TO GET USED TO IT, BUT I THINK IT'S NOT GOING TO -- I THINK BESIDES THE BUREAUCRATIC BURDEN WE DON'T THINK IT'S GOING TO HAVE A MAJOR EFFECT ON RESEARCH, AT LEAST WE HOPE NOT. OKAY. ANY QUESTIONS ON THAT ONE? YES, AMY. >> A QUICK QUESTION. WITH THAT, HAS THERE BEEN A REORGANIZATION OF WHEN CLINICAL TRIALS ARE CONSIDERED APPROPRIATE? IT WAS THOUGHT FOR A WHILE THAT MAYBE SAY FOR K23 AWARDS BY OLD DEFINITION A CLINICAL TRIAL MAY NOT BE THE BEST APPROACH, I'M ASSUMING AS WE MODIFIED THE CLINICAL TRIAL DEFINITION WE'VE MODIFIED THOUGHTS ABOUT WHAT -- THAT WILL BE CLARIFIED FOR K AWARDS, WHETHER THEY CAN INCLUDE WHAT IS NOW A CLINICAL TRIAL? >> STEVE, DO YOU WANT TO SAY ANYTHING ABOUT THAT? >> AS WITH MANY, THERE WILL BE TWO FOAS FOR EVERY MECHANISM, A CLINICAL TRIALS REQUIRED AND CLINICAL TRIALS NOT ALLOWED. THAT'S FOR LOTS OF MECHANISMS, TRAINING. >> THERE'S BEEN A LOT OF BUREAUCRACY ON OUR END TOO TRYING TO REDO FOAs. THIS IS AN FYI, I HOPE, AND SO AS YOU KNOW, ONE OF THE AGENCIES IN HEALTH AND HUMAN SERVICES, THERE IS AN EFFORT AT HEALTH AND HUMAN SERVICES TO REENGINEER THE FEDERAL WORKFORCE AND HOW WE DO WORK IN THE GOVERNMENT. AND SO THIS HAS COME TO NIH UNDER THE RUBRIC OPTIMIZE NIH, TO IMPROVE NIH OPERATIONS, BUSINESS PROCESSES, COORDINATION, AND MAXIMIZE EMPLOYEE FEEDBACK IN THE PROCESS. AND SO THIS IS SOMETHING THAT WILL I THINK BE COMING DOWN DIFFERENT STAGES AT NIH. I THINK WE ARE FEELING VERY FORTUNATE THAT OUR LEADERSHIP IN DISCUSSING WITH HHS HAS BASICALLY PUT TOGETHER A PLAN FOR HOW NIH CAN BE MORE EFFICIENT. THAT WAS BUILT AT NIH AND FORMED BY NIH, AND WE FEEL PRETTY CONFIDENT THAT THIS IS GOING TO BE A GOOD THING FOR US GOING FORWARD. WHAT THEY HAVE STARTED ALREADY IS STARTING A PLAN TO OPTIMIZE THE FUNCTIONS ACROSS THE DIFFERENT INSTITUTES, IN THESE THREE AREAS. ONE IS COMMITTEE MANAGEMENT WHICH KELLY BAKER IS LIKE AMAZING FOR US. ETHICS RUN BY MARTHA DIAZ ORTIZ, AND FOIA, FREEDOM OF INFORMATION, WE RELY ON NHLBI. NIH IS LOOKING AT BRINGING THOSE FOLKS TOGETHER, BEING MORE EFFICIENT BY CROSS-INSTITUTES WORK AS OPPOSED TO PURE INSTITUTE WORK BUT WE'LL SEE WHAT HAPPENS OVER TIME THERE. KELLY, HAVE YOU ANYTHING TO REPORT YET? IS IT STILL IN THE PLANNING STAGES? >> YEAH, WE'VE MET AND WE'RE DOING WORKING GROUPS. THAT'S IT. >> HIRING, THERE WAS A HIRING FREEZE. THE HIRING FREEZE WAS LIFTED BUT THE HIRING WAS THEN ONLY ALLOWED WHEN APPROVED BY DOWNTOWN HHS. AND THERE WERE VERY FEW HIRES. NINA WAS ONE OF THEM, THANK GOODNESS. WE WERE ABLE TO GET THAT THROUGH DOWNTOWN. DO YOU HAVE FRIENDS DOWN THERE? OKAY. ON OCTOBER 18, THE ABILITY TO HIRE WAS THEN TRANSFERRED BACK TO NIH, SO BUT AT NIH NOW I CAN'T DO THE HIRE MYSELF. IT HAS TO GO THROUGH APPROVAL PROCESS AT NIH CENTRAL. THERE'S A COMMITTEE THAT IS LOOKING AT ALL THE HIRES, AND THEY ARE LOOKING AT METRICS OF EFFICIENCY AND DETERMINING WHICH HIRES THEY ARE GOING TO APPROVE. AND THAT'S WHERE WE ARE NOW. BUT THINGS ARE CERTAINLY IMPROVING MONTH BY MONTH. WE HAVE A COUPLE SEARCHING -- SEARCHES OUT THAT ARE APPROVED. AS YOU KNOW WE HAVE THE DIVISION OF TRANSLATIONAL RESEARCH, CLINICAL RESEARCH, AND STARTED DIVISION OF NEUROSCIENCE, AND BOB AND DAVE HAVE BEEN ABLY LEADING THIS BUT WE HAVE A SEARCH FOR SOMEBODY WHO WOULD BE THAT DIVISION HEAD, AND THEN BOB AND DAVE WOULD BE THEN COORDINATING ACROSS ALL THE DIVISIONS, AND SO THAT SEARCH WE BELIEVE THEY ARE GOING TO BE INTERVIEWING FOLKS IN A COUPLE WEEKS, SO HOPEFULLY BY THE NEXT COUNCIL WE'LL HAVE SOMEBODY IN THAT SPOT AND WE'LL HAVE THREE DIVISION LEADERS THAT CAN WORK VERY CLOSELY TOGETHER, SCIENCE, TO MOVE OUR SCIENCE AND INTEGRATE OUR SCIENCE. THAT'S THE DIRECTION OF NEUROSCIENCE. THE SCIENTIFIC DIRECTORS FOR INTRAMURAL, THAT SEARCH WENT ON, ALLEN KORETSKY WANTS TO GO BACK IN THE LABORATORY. PEOPLE ARE LOOKING AND WE'RE HOPING TO FILL THAT SOON. BRAIN DIRECTOR JOB WE HAD A FAILED SEARCH BECAUSE OUR CHOICE COULDN'T CLEAR ETHICS, AND SO WE HAVE A NEW SEARCH GOING ON, A GREAT PROJECT, REALLY AMAZING PROJECT, AND A LEADER THERE WOULD BE INCREDIBLY IMPACTFUL ACROSS THE COUNTRY. WE HAVE A GREAT TEAM, NED FROM OUR END, GREG FARBER FROM NIMH, 20 OTHER PEOPLE IN NINDS WORKING ON THESE TEAMS, AND IT'S REALLY HUMMING. SO IT WOULD BE A REALLY EXCITING JOB. THE PERSON WHO DID THIS WOULD HAVE A LABORATORY AT NINDS SO THEY WOULDN'T HAVE TO GIVE UP THEIR LABORATORY WORK. SO IF YOU KNOW PEOPLE WHO MIGHT EVEN THINK ABOUT THIS, PLEASE WE'RE HAPPY TO TALK TO THEM. A COUPLE CHANGES ACROSS THE INSTITUTE, ROD PETTIGREW HEAD OF BIOENGINEERING LEFT TO JOIN TEXAS A & M UNIVERSITY. HE IS REPLACED IN ACTING STAGE BY JILL HEEMSKERK, PEOPLE REMEMBER WAS A FANTASTIC PROGRAM DIRECTOR IN OUR OFFICE OF TRANSLATIONAL RESEARCH, THEN WENT TO NIMH, AND THEN BECAME DEPUTY DIRECTOR AT NABIB. AND HER HUSBAND IS NICE TOO. [LAUGHTER] DAVE. JOSIE BRIGGS RETIRED, DAVID SHURTLEFF IS THERE. DAVID IS A PSYCHOLOGIST, PAIN RESEARCH, A NEURO BEND THERE. WE WENT FROM KIDNEY TO PSYCHOLOGY SO WE'LL SEE. WE HAVE A NEW HHS SECRETARY, DR. COLLINS HAS MET HIM. I HAVEN'T MET HIM YET. WE'RE LOOKING FORWARD TO HIM TAKING OVER AT HHS, COMES WITH A LOT OF EXPERIENCE, BOTH IN GOVERNMENT AND THEN IN INDUSTRY. OKAY. A COUPLE OF OTHER FYIs, I THINK IT WAS MONDAY MAYBE, OR TUESDAY, IT WAS ANNOUNCED OFFICIALLY THAT THE ACCELERATED MEDICINE PARTNERSHIP FOR PARKINSON'S DISEASE IS LAUNCHED. WE'VE ACTUALLY -- IS MARK SUTHERLAND HERE? HE'S BEEN WORKING HARD PUTTING THIS TOGETHER FOR YEARS, BUT FINALLY IT COMES TO FRUITION WHEN ALL THE PARTNERS SIGNED ON, SO THIS IS A 50-50 FUNDING PROGRAM, 50% OF THE MONEY FROM NIH, 50% OF THE MONEY FROM INDUSTRY, AND IT FOCUSES ON TRYING TO DEVELOP BIOMARKERS FOR FINDING TARGETS AND INFORMING PHASE 2 CLINICAL TRIALS IN PARKINSON'S DISEASE. WE HAVE AS WE'VE MENTIONED IN THE PAST NINDS HAS BEEN ASKED TO LEAD THE TRANS-NIH EFFORT TO TRY TO KICK START AND REALLY ENERGIZE RESEARCH IN CHRONIC FATIGUE SYNDROME, ME/CFS, AND WITH OTHER INSTITUTES AND THEIR FUNDING, AND PROGRAM DIRECTOR INPUT, WE HAVE FUNDED A CONSORTIUM OF CENTERS, HIGH LEVEL FOLKS TO LOOK SERIOUSLY AT THIS PROBLEM, TRY TO UNDERSTAND WHAT IS ITS ORIGIN, WHAT POTENTIAL TREATMENTS MIGHT BE CONSIDERED IN TRIALS. I DON'T KNOW IF PEOPLE HAVE SEEN THIS MOVE, UNREST, IT'S ON PBS ABOUT CHRONIC FATIGUE SYNDROME. IT'S A PRETTY POWERFUL FILM, EMOTIONALLY POWERFUL FILM. IF YOU GET A CHANCE TO SEE IT, IT WOULD BE INTERESTING. THE BIG PROBLEM, I LIKE PEOPLE TO THINK ABOUT THIS, IF THERE'S ANYTHING THAT BOTHERS ME THE MOST BEING NIH DIRECTOR SEEING WHAT'S GOING ON IN TERMS OF THE OPIOID OVERDOSE DEATHS, AND FEELING HELPLESS AND NOT ONLY HELPLESS BUT KIND OF GUILTY THAT THE EFFORT THAT'S BEEN MADE ON THE PART OF NIH AND MAYBE THE REST OF THE HHS TO SOLVE THIS PROBLEM JUST IS NOTHING CLOSE TO WHAT IT NEEDS TO BE. SO 63,000 PEOPLE DIED OF OVERDOSE LAST YEAR. SO THAT'S MORE THAN DIED AT THE PEAK OF THE AIDS EPIDEMIC. NOW, THERE'S $3 BILLION OF RESEARCH MONEY FOR AIDS WHICH WAS MANDATED BY CONGRESS WHEN THIS WAS KILLING PEOPLE. THERE'S STILL $3 BILLION OF RESEARCH FOR AIDS MONEY. THERE IS VERY LITTLE -- THERE'S BEEN NO EXTRA MONEY FOR THIS PROBLEM. AND SO AT SOME POINT, I THINK IT SHOULD HAVE BEEN A YEAR OR TWO AGO, NIH HAS GOT TO RESPOND TO THIS. AND HOW TO DO THIS IN THE MOST EFFECTIVE WAY, IT'S NOT CLEARLY NOT JUST AN NIH PROBLEM BUT EVERYBODY SAYS THE MEDICAL PEOPLE SAY IT'S NOT OUR PROBLEM, YOU KNOW, WE'VE BEEN DOING BETTER IN TERMS OF PRESCRIBING. CDC IS DOING SURVEILLANCE, THAT WE CAN'T DO THE TREATMENT. SOMEHOW WE HAVE TO KIND OF GET THE GROUPS TOGETHER. DR. COLLINS HAS BEEN REALLY PUSHING HARD ON THIS FOR THE LAST SIX MONTHS, AND WE'VE BEEN MEETING WITH HIM, LINDA PORTER AND I, WITH DR. VOLKOW WEEKLY ON A PLAN THAT HE'S GOING TO TALK TO YOU ABOUT COMING UP. BUT I THINK WE ALSO NEED SOME NEW IDEAS ON WHAT WE SHOULD BE DOING IN THIS SPACE BECAUSE THE DEATHS ARE HORRIBLE. THAT'S JUST THE TIP OF THE ICEBERG. FOR EVERYBODY WHO DIES, THERE'S GOT TO BE 50 OTHER PEOPLE WHO ARE ADDICTED. AND CAN'T HAVE NORMAL LIVES. ADDICTION IS A BRAIN CIRCUIT DISORDER. PEOPLE HAVE DEALT WITH -- PEOPLE WHO HAVE ADDICTION, THE BRAIN IS REWIRED. YOUR REWARD SYSTEM IS COMPLETELY DIFFERENT AFTER YOU'VE BEEN EXPOSEED TO THESE DRUGS. SO IT IS A BRAIN PROBLEM, AND NIDA IS IN THE LEAD THERE. WE'RE REALLY IN THE LEAD FOR PAIN. AND TREATMENT OF PAIN. AND THE TREATMENT OF PAIN IS WHAT GOT US INTO THIS MESS IN THE FIRST PLACE, INCREASED USE OF PRESCRIPTION OPIOIDS. AND SO IF, FOR INSTANCE, IF YOU WANTED TO SHUT THIS OFF, IF YOU COULD SUBSTITUTE A NON-ADDICTIVE PAIN MEDICINE FOR OPIOID, THAT I THINK WOULD BE A MAJOR PUSH. THAT'S WHAT DR. COLLINS IS PUSHING US TO THINK ABOUT. A COUPLE OF ADVANCES, SO RECENTLY THIS STUDY CAME OUT IN THE NEW ENGLAND JOURNAL AND IT'S A STUDY THAT USED AN IMAGING TECHNIQUE CALLED PERFUSION DEFUSIO IMAGING, CT IMAGING, IT WAS ABLE TO TAKE PEOPLE WHO CAME WITH A STROKE, IMAGE THEM AND DETECT WHETHER THEY HAD NO TISSUE TO SALVAGE OR LOTS OF TISSUE TO SALVAGE. EVERYBODY AT THIS STAGE HAS SOME TISSUE THAT'S DEAD AND YOU'RE NOT GOING TO SALVAGE. SOME PEOPLE IT'S ALL DEAD, AND THE DEAL IS DONE UNFORTUNATELY. SOME PEOPLE HOWEVER EVEN AT LATE TIME PERIODS THERE'S TISSUE TO SALVAGE. AND THIS TECHNOLOGY, THIS IMAGING TECHNOLOGY, WHICH WE'VE KIND OF BEEN FUNDING, THIS STUDY IS DIFFUSE 3, WE FUNDED 1 AND 2 TO DEVELOP THIS TECHNOLOGY, AND NOW DEFUSE 3, THEY TOOK PEOPLE IN WHO ARE LATE ON AFTER SIX HOURS OF STROKE ONSET, PREVIOUSLY THOSE PEOPLE WERE NOT TREATED, AND SHOWED WITH THIS IMAGING THEY COULD PICK PEOPLE OUT AND WITH THIS IMAGING LOTS OF TISSUE TO SALVAGE, AND HAVE A HUGE EFFECT SIZE. SO I THINK IT WAS LIKE 41% BECAME INDEPENDENT IN TREATED GROUP VERSUS 17% IN UNTREATED GROUP. SO IT'S A TREMENDOUS EFFECT SIZE. AND SO I THINK THAT ACTUALLY THAT SAME TECHNOLOGY WAS USED IN ANOTHER TRIAL THAT WAS INDUSTRY SPONSORED BY RAGULENAGAR SHOWING A SIMILAR THING, THIS IN ADDITION TO THE 2015 STUDIES OF ENDOVASCULAR THERAPY, TAKING CLOTS OUT IN STROKE PATIENTS EARLY, SHOWING TREMENDOUS BENEFIT HAS REALLY COMPLETELY CHANGED HOW STROKE IS GOING TO BE MANAGED. IT'S GOING TO BE JUST REALLY VERY SIMILAR TO HEART ATTACK, GET PEOPLE INTO THE CATH LAB AS FAST AS YOU CAN, GET THE CLOT OUT, AND DEVELOP SOME WAY OF SELECTING PATIENTS WHO STILL CAN BENEFIT FROM THIS FAIRLY AGGRESSIVE THERAPY. AND I GUESS THE ONLY OTHER POINT TO MAKE IS THAT I WAS INVOLVED IN THIS IN THE BEGINNING, I GAVE A TALK AT THE AMERICAN HEART ASSOCIATION, AND BASICALLY THE PREMISE THAT THIS WAS GOING TO WORK CAME -- PUBLISHED IN 1996. IT TOOK 21 YEARS FROM THE INITIAL DISCOVERY TO ACTUALLY SHOWING BENEFIT IN PEOPLE, AND HOW TO SHORTEN THAT TIME IS CERTAINLY INTERESTING. I'D ALSO SAY IN TERMS OF CLINICAL SIDE OF THINGS A COUPLE INTERESTING THINGS HAVE HAPPENED. SO WE HAVE A STROKE TRIAL, OF A DRUG, IT'S AN ACTIVATED PROTEIN C MODIFIED DRUG THAT WAS THOUGHT TO PROTECT THE BRAIN FROM REPERFUSION INJURY, AND THAT WAS RUN BY OUR NEURO NEXT NETWORK, THEY REPORTED THE DRUG DECREASED HEMORRHAGE RATE FOR PEOPLE TREATED FOR ACUTE STROKE. ANOTHER TRIAL FOR MULTIPLE SCLEROSIS, A PHASE 2, OUTCOME TO DECREASE ATROPHY IN THE BRAIN IN PEOPLE WITH MULTIPLE SCLEROSIS, THAT ALSO MET ITS OUTCOME SO THOSE ARE NOT PUBLISHED, PHASE 2, WHERE WE TRY TO FOCUS, BUT LOOK PRETTY PROMISING FROM THE INVESTMENT WE MADE THERE. WE HAVE TRYING TO GET THE WORD OUT ABOUT HOW AS THESE THINGS COME OUT 20 YEARS AFTER WE FIRST INVESTED IN THEM, HOW DO YOU ACTUALLY TIE THIS THERAPEUTIC ADVANCE THAT PEOPLE RECOGNIZE AS THE END GOAL OF NIH'S BASIC RESEARCH TO TRANSLATIONAL TO CLINICAL RESEARCH. WE HAVE A WEBSITE THAT WE'RE WORKING ON, TRYING TO PUT STORIES UP. SMA STORY AND tPA STORY NOW, BUT AS THESE COME UP WE'RE GOING TO TRY TO PUT THAT OUT THERE AND BUT I'D ENCOURAGE FOLKS WE ARE VERY POOR AT MESSAGING TO THE PUBLIC ABOUT THE VALUE OF NIH. PEOPLE AROUND THE TABLE, PEOPLE IN UNIVERSITIES, PEOPLE IN YOUR FOUNDATIONS, THEY ARE THE ONES WHO CAN REALLY DO THIS WELL. AND SIMILARLY AMY ADAMS' GROUP IS WORKING ON A NEW WEBSITE DESIGN WHICH IS UP. AND A NEW PUBLIC SIDE WHERE WE'RE GOING DO HAVE -- KIND OF PUT OUR PUBLIC INFORMATION MESSAGES UP. MOST OF THEM HAVE BEEN INVOLVED IN STROKE. WE HAVE ONE COMING UP IN CHILDHOOD MIGRAINE. I WANT TO MOVE TO THE BRAIN INITIATIVE. I MENTIONED THAT ABOUT THE 21ST CENTURY CURES ACT HAD FUNDING FOR THE BRAIN INITIATIVE TO 2026, SEEN IN GREEN. IN BLUE IS SEEN THE FUNDING THAT'S COME FROM CONGRESS TO THE BASE OF THE INSTITUTES, WE GET MAYBE A LITTLE LESS THAN HALF OF THIS MONEY TO NINDS, AND THIS IS INTO THE BASE, SO WE CURRENTLY HAVE $250 MILLION FOR THE BRAIN INITIATIVE INTO THE BASE, THIS IS ADDITIONAL FUNDING, NOT COMING OUT OF THE R01 POOL, AND THEN THIS IS THE PROJECTED 21ST CENTURY CURES FUNDING WHICH GETS US TO $400 MILLION A YEAR, WITH THIS ONE PEAK IN 2023. AND THAT'S ACTUALLY PRETTY CLOSE TO WHAT WAS CALLED FOR IN THE PROFESSIONAL JUDGMENT. IT WAS HIGHER. WE'RE HOPING WE CAN GET GREATER FUNDING TO THE BASE OVER THE YEARS, BUT THIS LOOKS VERY, VERY EXCITING GOING FORWARD. THE BRAIN INITIATIVE ITSELF HAS BEEN TREMENDOUSLY TRANSFORMATIVE I THINK IF YOU SEE THE TYPE OF RESEARCH THE PEOPLE ARE DOING TO UNDERSTAND CIRCUIT ACTIVITY, THINGS YOU COULD ONLY IMAGINE DOING YEARS AGO AND ACTUALLY TOM SUDHOFF WAS HERE YESTERDAY, GAVE A TALK, I DON'T KNOW IF HE -- HE WROTE A PAPER IN NEURON, THE BRAIN CIRCUIT FIELD IS MOVING SO FAST HE THINKS MAYBE WE SHOULD BE A LITTLE CAREFUL, THE PENDULUM MAY SWING TOO FAR AND AWAY FROM MOLECULAR NEUROSCIENCE WHICH WAS THE BURGEONING FIELDS FROM THE '70s TO NOW. THE CIRCUIT FIELD WAS REALLY HELD BACK BY THE FACT THEY HAD POOR TECHNOLOGIES. BUT I THINK I'M NOT WORRIED, I THINK THAT BALANCE WILL OCCUR. AND BUT IT IS -- IT WAS GREAT TO THINK ABOUT HOW TO MARRY THOSE TWO. THE BRAIN INITIATIVE MEETING IS COMING UP IN APRIL. ALL THE BRAIN P.I.s COME IN FROM US, NIH, NATIONAL SCIENCE FOUNDATION, DARPA AND IARPA-FUNDED FOLKS AND IT'S A REALLY EXCITING MEETING, AND ANYBODY WOULD BE WELCOME. WE ARE ABOUT TO OPEN UP A COMMITTEE AGAIN. WE HAD A COMMITTEE THAT GAVE US THE KIND OF BIBLE FOR WHAT THE LIKE. IT WAS CALLED THE BRAIN 2025 REPORT. THAT'S AVAILABLE ONLINE. WE'VE KIND OF PRETTY WELL STUCK CLOSE TO THAT. IT'S EXTREMELY -- WE FOUND IT EXTREMELY VALUABLE AND SCHOLARLY. BUT THINKING ABOUT THE FUTURE, NEXT HALF OF THE BRAIN INITIATIVE, WHERE MOST OF THE FUNDING IS, WE'RE GOING TO THINK ABOUT GETTING A GROUP TOGETHER AND LOOKING AT WHAT WE'VE DONE, WHAT THE OPPORTUNITIES FOR THE FUTURE LOOK LIKE, AND SHOULD WE REVISIT THINGS IN THE BRAIN 2025 REPORT. I WANT TO TALK I THINK CONSIDERABLE TIME INTO THIS ISSUE OF THE NEUROETHICS QUESTIONS THAT ARE BEING RAISED AS THE BRAIN INITIATIVE WORK MOVES FORWARD. SO WHEN THE BRAIN INITIATIVE WAS FIRST ANNOUNCED, IT IS, REMEMBER, AN EFFORT TO DEVELOP THE TECHNOLOGIES TO MONITOR AND MODULATE BRAIN CIRCUIT FUNCTION. AND SO FOR DISEASES, THAT'S WHAT IT'S ALL ABOUT, IN A SENSE. IF YOU'RE THE PATIENT, YOU WORRY ABOUT THE SYMPTOM THAT YOU HAVE. MY MEMORY IS POOR, MY MOTOR FUNCTION IS POOR, AND THOSE SYMPTOMS ARE A DIRECT RELATION TO THE ABNORMAL CIRCUIT FUNCTION. NOW, THAT CIRCUIT FUNCTION COULD BE DISORDERED FOR TAU BUILDING UP AND KILLING NEURONS OR A STROKE AND PARTICULARLY A PATHWAY, BUT THE ACTUAL DEFICIT IS RELATED TO THE CIRCUIT DYSFUNCTION. AND FOR SOME DISORDERS LIKE STROKE AND ALZHEIMER'S WE CAN LOOK IN THE BRAIN AND SEE WHAT THE MOLECULAR AND PATHOLOGY IS BEHIND THE DISORDER, AND ASSUME THAT'S AFFECTING THE CIRCUIT, BUT A LOT OF ASSUMPTIONS THERE, LOTS OF CASES WHERE YOU CAN SEE A BRAIN FULL OF AMYLOID AND TAU AND THE PERSON HAS NORMAL MEMORY FUNCTION. SO THERE'S OFTEN DISCONNECT THAT WE TEND TO IGNORE. BUT FOR MANY DISORDERS WHEN YOU LOOK IN THE BRAIN YOU DON'T SEE ANYTHING AND DON'T HAVE ANYTHING TO GO AFTER. THAT ACCOUNTS FOR SOME OF THE DISORDERS WE HAVE, YOU KNOW, TOURETTE'S SYNDROME, DYSTONIA, YOU CAN'T REALLY SEE WHAT'S GOING ON. CLEARLY THE CIRCUITS ARE VERY ABNORMAL. PAIN IS A PURELY CIRCUIT DISORDER. IT'S A GOOD THING TO HAVE TO AVOID INJURY BUT CHRONIC PAIN IS NOT A GOOD THING. BUT THERE IS NO PATHOLOGY TO BE SEEN. AND THEN ALL THE PSYCHIATRIC DISORDERS FALL INTO THAT CONDITION. SO THEY ARE ALL BRAIN DISORDERS, THEY ARE CALLED PSYCHIATRIC DISORDERS BECAUSE WHEN YOU LOOK IN THE BRAIN YOU DON'T SEE ANYTHING. IF YOU LOOKED IN THE BRAIN AND SAW SOMETHING WE CALLING THAT NEUROLOGIC DISORDER. ONCE WE SEE THE BRAIN CIRCUITS THEY ARE ALL GOING TO BE NEUROLOGIC DISORDERS. SO THAT'S REALLY THE MANDATE FOR DOING THIS PROGRAM. BUT ON THE OTHER HAND, YOU'RE DEVELOPING TECHNOLOGIES TO MONITOR AND MODULATE BRAIN CIRCUITS, SO WHEN THAT GETS TO PEOPLE, MONITORING PEOPLE'S BRAIN CIRCUITS, OR MODULATING PEOPLE'S BRAIN CIRCUITS, THEY ARE GOING TO BRING UP QUESTIONS IN THE MEDICAL SPACE, YOU KNOW, WHAT'S THE BENEFIT, WHAT'S THE RISK, WHAT'S THE DOWN SIDE OF DOING THAT? AND THE NON-MEDICAL SPACE, IT COULD BE THE WILD WEST. SO DEVELOPING WAYS IN WHICH YOU CAN MODULATE BRAIN FUNCTION SO THAT KIDS LEARN MATH BETTER. I THINK THAT'S PROBABLY POSSIBLE. WE'LL GET TO THAT. BUT THEN ENHANCING OTHER TYPE OF ABILITIES MAY BE QUESTIONABLE. PARTICULARLY IF YOU GET INTO THINGS WHERE IT'S ENHANCING ONE PERSON WHERE SOMEONE ELSE LOSES OUT BECAUSE OF THAT ENHANCEMENT, WHETHER IT'S ON MILITARY SIDE OR LAW ENFORCEMENT SIDE OR WHATEVER. SO THAT'S THE ISSUE WITH THE MODULATION. THE MONITORING IS THE ISSUE OF PRIVACY. SO WHEN WE STARTED, THE PRESIDENT ACTUALLY INSTRUCTED HIS BIOETHICS COMMISSION TO LOOK AT THE BRAIN INITIATIVE TYPE OF WORK, THIS IS BEFORE IT EVEN STARTED, AND THEY PUT OUT A REPORT WHERE THEY RAISED THE ETHICAL QUESTIONS THAT WE HAVE TO CONSIDER. WHEN WE STARTED THE BRAIN INITIATIVE WE PUT TOGETHER A NEUROETHICS GROUP PART OF OUR MULTI-COUNCIL WORKING GROUP THAT ADVISES US IN THE BRAIN INITIATIVE AND THEY HAVE BEEN WORKING WITH FORESIGHT TO PUT DOWN THE PRINCIPLES THAT SHOULD BE GUIDING US AND ALSO TO HELP US WHEN THERE IS AN ISSUE THAT NEEDS DEEP DIVE AND STRONGER CONSIDERATION. SO THE FIRST THING I'M GOING TO TALK ABOUT IS THAT THEY HAVE A DRAFT, WHAT'S CALLED NEUROETHICS GUIDING PRINCIPLES FOR NIH BRAIN INITIATIVE, AND I'M GOING TO EXPLAIN THIS AND I THINK WE'LL DISTRIBUTE IT TO THE COUNCIL MEMBERS FOR YOUR INPUT. SO, THE IDEA IS THAT WE WANT TO HAVE KIND OF AN OVERARCHING SET OF PRINCIPLES THAT CAN BE PUT DOWN ON PAPER TO GUIDE THE BRAIN INITIATIVE RESEARCH GOING FORWARD. AND BUT THESE ARE TO TRY TO ENSURE THE ETHICAL CONDUCT OF BRAIN RESEARCH, AND TO THINK ABOUT THE ETHICAL AND SOCIETAL IMPLICATIONS OF THE DISCOVERIES AND NEW TECHNOLOGIES THAT THE RESEARCH WILL SPAWN. AND AS I SAID IN THE BEGINNING WE THINK THAT ONE OF THE MOST IMPORTANT ETHICAL PRINCIPLES IS THAT WE REALLY NEED TO DO THIS, THAT TO TRY TO TREAT THE DISORDERS I TALKED ABOUT WE NEED TO KNOW THIS KIND OF INFORMATION. AND WE'RE STUCK BECAUSE WE DON'T HAVE IT. ON THE OTHER HAND, WE ALSO WANT TO SAY NEUROETHICS IS VITAL TO NEUROSCIENCE RESEARCH, THAT IF THIS IS NOT DONE ETHICALLY IT'S GOING TO STOP. AND WE REALLY WANT TO MAKE SURE THAT AS THE RESEARCH GOES ON, PEOPLE ARE THINKING ABOUT ISSUES AND NOT GOING TO A PLACE WHERE WE THINK IS DANGEROUS OR NOT IN THE BEST INTEREST OF SOCIETY. OKAY. THESE ARE THE PRINCIPLES. I WOULD SAY WHEN YOU SEE THEM, YOUR FIRST THOUGHT IS, WELL, THESE ARE MILK TOAST, AND THE TRUTH OF THE MATTER IS THEY ARE IN THE SENSE MILK TOAST BECAUSE I THINK THEY HAVE PRETTY MUCH WIDE AGREEMENT THAT THESE ARE IMPORTANT AND THERE'S NOT A LOT OF DISAGREEMENT. BUT I THINK IT'S STILL IMPORTANT TO GET THEM OUT THERE BECAUSE IF SOMETHING IS GOING TO CROSS THE LINE IT'S GOING TO CROSS ONE OF THESE LINES. AND SO TO PUT THE LINES OUT THERE I THINK IS IMPORTANT TO BEGIN WITH. SO FIRST THING IS SAFETY. AND THAT, YOU KNOW, I THINK IS PRETTY CLEAR-CUT. PEOPLE UNDERSTAND THAT. BUT IN THE BRAIN INITIATIVE THERE ARE AREAS OF SAFETY THAT WE MAY NOT HAVE THOUGHT ABOUT BEFORE. SO THE ONE THING WE HAVE IS PEOPLE WHO ARE RECORDING FROM PATIENTS WHO UNDERGO EPILEPSY, DEEP BRAIN STIMULATION, AND THE RISK IS MINIMAL BUT IT'S NOT ZERO TO HAVE ANOTHER ELECTRODE PUT IN OR HAVE ELECTRODES PLACED OVER THE CORTEX WHILE YOU'RE STIMULATING WITH AN ELECTRODE STRIP IN THE BASAL GANGLIA. IT'S MINIMAL BUT IT'S AN AREA THAT CONSENT PROCESSES HAVE TO BE THERE. IT'S NOT JUST, OH, WE'RE IN THERE, WE'LL JUST PUT THIS IN AND DON'T WORRY ABOUT IT. IT'S GOT TO BE REALLY EXPLAINED IN DETAIL WHAT THE SAFETY ISSUES ARE. THERE MAY BE CHANGES WE DON'T KNOW ABOUT IN TERMS OF MODULATING BRAIN CIRCUITS, WE KNOW WHEN PEOPLE DO BRAIN STIMULATION FOR PARKINSON'S DISEASE THERE WERE PERSONALITY CHANGES THAT OCCURRED THAT WEREN'T ANTICIPATED AND BUT WERE DISCOVERED AND THOSE THEN HAVE TO BE EXPLAINED AS BEST AS POSSIBLE AS RISKS AS YOU GO ON. THAT GETS YOU INTO THE NEXT SIDE WHICH IS THE BRAIN INITIATIVE BRINGS UP QUESTIONS OF AUTONOMY, AGENCY AND CAPACITY. THE PERSON WHO HAS DEEP BRAIN STIMULATION WHICH MAKES THEM MORE, SAY, MANIC OR RISK -- LESS RISK ADVERSE, THEY MAY LIKE THAT. BUT THAT'S NOT WHY WE PUT IT IN. WE PUT IT IN FOR THE PARKINSON'S DISEASE. SO WHO CONTROLS THAT DECISION? IS IT THE PATIENT? IS IT THE DOCTOR? IS IT THE FAMILY? THAT KIND OF DISCUSSION IS NOT SOMETHING THAT YOU CAN EASILY KIND OF PUSH OFF. THAT'S GOT TO BE A SERIOUS TYPE DISCUSSION. THERE WILL BE LOTS OF THOSE KIND EVER THINGS THAT COME. CONFIDENTIALITY AND PRIVACY OF THOUGHTS, NEURODATA IS IMPORTANT. JIM EBERLINE USES THE ANALOGY, PEOPLE ARE TAKING BRAIN TISSUE FROM PEOPLE WHO HAVE EPILEPSY SURGERY, THEY ARE ABLE TO RECORD FROM THE DISH. WHAT IF I RECORD THE NEURON THAT HAS THE MEMORY OF THE PERSON'S FIRST KISS? AND WOULD I TELL THE WIFE? SO TO BE FACETIOUS, THOSE THINGS, EXAMPLES, THEY COULD REALLY GET CERTAIN PEOPLE NOT INFORMED THAT'S NOT GOING TO BE POSSIBLE AT THIS POINT IN TIME, NOT SOMETHING TO WORRY ABOUT BUT IT GETS YOU THE QUESTION OF WHAT ORGANIZATION, WHAT FUNCTION WOULD YOU SEE THAT WOULD START GETTING YOU WORRIED ABOUT THINGS LIKE THAT? STEVE HYMAN SAYS, WELL, IF THE CULTURE BASICALLY PICKS UP THE PHONE AND CALLS THEIR LAWYER YOU'VE GONE TOO FAR. BUT THAT'S AGAIN THE FACETIOUS EXAMPLE. IN TERMS OF THOUGHTS, THERE ARE WAYS WITH fMRI NOW WHERE YOU CAN LOOK AT VISUAL CORTEX AND GET A GOOD SENSE OF WHAT THE PERSON HAS BEEN LOOKING AT. SO YOU CAN EVEN NOW WITH TECHNOLOGIES WE HAVE GET SOME IDEAS OF READOUT FROM CIRCUIT FUNCTION. AND THEN I THINK AS I MENTIONED BEFORE, I THINK THE MEDICAL COMMUNITY HAS BEEN FACED WITH MANY TECHNOLOGIES OVER THE YEARS, AND THEY HAVE OFTENTIMES RUN A PATH THAT GOES BACK AND FORTH UNTIL THEY GET ON THE STRAIGHT AND NARROW. I FEEL COMFORTABLE IN MEDICINE WE'RE GOING TO DO THIS BUT OUTSIDE OF MEDICINE I THINK THAT'S WHERE WE HAVE VERY LITTLE TO PLAY, ROLE TO PLAY, BUT WE HAVE TO INFORM SOCIETY ON HOW THIS IS TO BE USED PROPERLY. AND WE HAVE TO BE CAREFUL AS WE MOVE THESE TOOLS AND TECHNOLOGIES INTO THE MEDICAL SPACE OR NON-MEDICAL SPACE. AGAIN, VERY SIMILAR TO OTHER TECHNOLOGIES MOVED IN, OFTENTIMES THEY MOVE IN AND GO TOO FAR AND GET PULLED BACK. AND THEN YOU FIND THE REAL SPOT WHERE THEY ARE REALLY ADVANTAGEOUS. SO THAT PROCESS I THINK IS GOING TO OCCUR HERE TOO. NOW, WE HAVE TO -- NOW THE OTHER PART WHICH I THINK IS AGAIN HARDER FOR NIH IS TO TRY TO ACTUALLY DISCUSS WITH THE PUBLIC ABOUT THESE ISSUES IN A KIND OF LOGICAL FASHION AND STAY AWAY FROM THE SCIENCE FICTION SIDE OF THINGS, AND THIS IS GOING TO BE A MESSAGING TASK I THINK AND WE CERTAINLY AGAIN NOT SOMETHING THAT NIH IS REALLY GOOD AT SO WE NEED TO ENGAGE OTHERS TO KIND OF GET THAT INFORMATION OUT TO KEEP THE PUBLIC INFORMED, AND THE LAST ONE IS TO BEHAVE JUSTLY, WHICH MEANS TO REALLY LOOK AT WHAT THE PROS AND CONS ARE OF ANY TECHNOLOGY AND USE THEM WISELY SO THAT THE BENEFIT OUTWEIGHS THE RISK. SO THAT'S BASICALLY THE BRAIN INITIATIVE NEUROETHICS GUIDING PRINCIPLES TO START. AND THEN WHAT WE'LL HAVE AT DIFFERENT STAGES, DEEP DIVES INTO PARTICULAR ISSUES. WE'VE HAD WORKSHOPS ON CONSENT, ON EX VIVO BRAIN RESEARCH, AND CONSENT WITH INVASIVE DEVICES. ANYBODY HAVE QUESTIONS ON THIS ONE? WE'LL SEND THIS DRAFT AROUND AND LOOK FOR COMMENTS, THIS OFFICIALLY WILL BE A REPORT TO THE MULTI-COUNCIL WORKING GROUP THAT WILL COME TO OUR COUNCIL FOR APPROVAL. ALMOST DONE. EVERY YEAR AT NIH THE PROGRAM DIRECTORS AND OFFICE OF DIRECTOR LOOK BACK AT SOME OF THE ADVANCES OVER THE LAST YEAR AND YOU ALWAYS ARE AMAZED TO SEE THE AMOUNT AND REALLY EXCITING NEW SCIENCE THAT COMES OUT. SO WE HAVE A WEB PAGE UP, WHICH IS LOOKING BACK, WE PICKED TEN THINGS, THEY ARE NOT THE TOP TEN, JUST TEN GOOD THINGS OF PROBABLY A MILLION GOOD THINGS. SO I THINK THIS IS THINGS TO LOOK AT. INTERESTING FROM ED BOYDEN, HE'S BASICALLY STIMULATING THE BRAIN, ELECTRICALLY AT HIGH FREQUENCIES THAT DON'T ACTIVATE NEURONS, BUT THEN FOR MULTIPLE POINT SOURCES SO WHEN THEY CONVERGE THERE'S A LOWER FREQUENCY THAT RESONATES THAT DOES TURN ON NEURONS. NOW, SO YOU CAN DO THIS, YOU WOULD BE ABLE TO TURN ON NEURONS ANYWHERE IN THE BRAIN, WITH THIS KIND OF FOCUSED MULTI-FOCUSED ELECTRICAL STIMULATION. I THINK IT'S STILL EARLY DAYS TO KNOW IF WE CAN PULL THIS OFF, BUT PRETTY AMAZING, PRETTY AMAZING FINDING. THE LAST ONE FROM THE BARRIS LAB, BEN WAS EXCITED HE THOUGHT HE FOUND A SWITCH WHEREBY ASTROCYTES WHO ARE GENERALLY SUPPORTIVE OF A LOT OF NEURONAL FUNCTIONS SWITCH INTO A TOXIC STATE AND PRODUCE TOXIN THAT GETS OUT OF THE ASTROCYTES AND KILLS THE NEURONS. SO HE HAS A PAPER THAT INDICATES THIS IS TRUE, THEY HAVEN'T ACTUALLY IDENTIFIED THE TOXIN, AND UNFORTUNATELY AS PEOPLE KNOW BEN DIED RECENTLY, SO HE WAS COUNCIL MEMBER, AND REMEMBER HE'S THE ONE WHO COULD NEVER REALIZE HOW TO HIT THE BUTTON TO TALK. A REALLY WONDERFUL PERSON. I HAD THE OPPORTUNITY TO WORK WITH HIM IN THE LAB FOR FIVE OR SIX YEARS. AND HE WILL BE SORELY MISSED. AND BUT I THINK HIS LEGACY LIVES ON, AND HE CERTAINLY HAD AN IMPACT HERE AT NINDS. WITH THAT I WOULD LIKE TO CLOSE THE DIRECTOR'S MESSAGE. BUT HAPPY TO ANSWER QUESTIONS. I GUESS WE'RE NOT HAPPY TO ANSWER QUESTIONS. OKAY. GRAB ME IF YOU HAVE ISSUES. OKAY. >> SO A COUPLE OF COUNCIL MEMBERS ASKED ME A LITTLE WHILE AGO IF WE COULD HAVE A TIME TODAY TO TALK ABOUT THINGS THAT SHOULD BE ON THE AGENDA. SO THE ANSWER IS IF WE CAN STAY ON SCHEDULE WE COULD SPEND 15 MINUTES STARTING THAT IN OPEN SESSION BUT IF YOU HAVE OTHER IDEAS YOU CAN E-MAIL THEM TO US AND WE CAN TALK ABOUT THEM. SO AT THE END OF THE OPEN SESSION IF IT'S NOT LATER THAN ABOUT 2:00 OR QUARTER TO 2:00, WE CAN DO THAT. SO WE USE ALL -- ALL INSTITUTES DON'T DO THIS BUT WE USE COUNCIL FOR CONCEPT CLEARANCE FOR NEW INITIATIVES THAT INVOLVED NINDS MONEY. SO ESSENTIALLY WE HAVE A BUNCH OF INITIATIVES TODAY, MORE THAN THE USUAL NUMBER, AND I'LL JUST CUT INTO THIS. THE FIRST INVOLVES A PROPOSED TRANSLATIONAL T32 PROGRAM THAT STEVE AND I BELIEVE AMIR ARE GOING TO DISCUSS. STEVE KORN IS HEAD OF OUR TRAINING OFFICE. >> GOOD MORNING. WE'VE GOT TO DRAP TO DROP DOWN TO THE GROUND FROM 30,000 FEET TALKING ABOUT INITIATIVES. THIS IS AS BOB MENTIONED FOR TRANSLATIONAL TRAINING PROGRAM. IT'S A JOINT EFFORT BETWEEN THE TRAINING OFFICE AND THE DIVISION OF TRANSLATIONAL RESEARCH, AND IT'S A SOMEWHAT LIMITED BUT WE THINK IMPORTANT OPPORTUNITY. SO THIS IS ABOUT CREATING SOME T32s, AND IT IS REALLY WE WANT TO PUT OUT AN FOA TO STIMULATE SUBMISSION OF APPLICATIONS FOR TRANSLATIONAL RESEARCH. SO WHAT WE ENVISION THESE PROGRAMS IS DOING IS SUPPORTING BASIC DISEASE-RELATED RESEARCH PROJECTS. AND IT WOULD BE FOR ADVANCED STUDENTS AND POSTDOCS, BUT IT'S A WAY OF FORMING GROUPS BETWEEN BASIC SCIENTISTS AN CLINICIANS TO DO BASIC RESEARCH WITH AN EYE TO TRANSLATION. HOW DO YOU DO RESEARCH THAT YOU CAN THEN MOVE FORWARD TOWARDS CLINICAL APPLICATION? JUST TO GIVE YOU AN IDEA WHAT THE PORTFOLIO LOOKS LIKE, I'VE LISTED FROM 2008 TO THE PRESENT THAT'S A TOTAL NUMBER OF APPLICATIONS FOR T32s, 239, TWO WERE WHAT YOU COULD ARGUE WOULD BE TRANSLATIONAL, ONE OF THOSE IS ARGUABLE. THERE ARE A COUPLE ENGINEERS I DID NOT INCLUDE IN THE NUMBERS. YOU COULD ARGUE THEY ARE TRANSLATIONAL. BUT THE WAY WE'RE THINKING OF IT, THEY ARE NOT. WE'VE FUNDED ONE, AN OUTSTANDING PROGRAM THAT DOES EXACTLY WHAT WE'RE TRYING TO STIMULATE. BUT WE JUST ESSENTIALLY GET NO APPLICATIONS TO DO THIS SORT OF THING. WHY WOULD WE DO IT? THERE ARE LOTS OF TRAINEES THAT WOULD LIKE TO DO IT. THEY DON'T REALLY HAVE THE OPPORTUNITY IN A PROGRAMMATIC WAY. THERE MAY BE INDIVIDUALS IN INDIVIDUAL LABORATORIES DOING THIS. BUT THE OPPORTUNITY IS NOT THERE FROM A PROGRAMMATIC LEVEL. LOTS OF STUDENTS DOING BASIC RESEARCH WOULD LIKE TO THINK ABOUT CLINICAL APPLICABILITY OF THEIR RESEARCH AS OPPOSED IT TO BEING PURELY BASIC DISCOVERY. BUT THEY JUST DON'T HAVE THE OPPORTUNITY. AND AS I MENTIONED THERE ARE VERY FEW PROGRAMS THAT DO THIS THAT LIST THESE BULLETS HERE, FOR WHAT THEY ARE DOING. IT'S FOCUSING ON TRANSLATIONAL PRINCIPLES. I MEAN, REALLY THAT'S WHAT THIS IS ABOUT. HOW DO YOU DO BASIC SCIENCE WITH AN UNDERSTANDING OF HOW YOU WOULD MOVE YOUR WORK FORWARD TOWARDS CLINICAL APPLICABILITY? AND SO THESE PROGRAMS WOULD CREATE AN ENVIRONMENT TO DO THAT, AND PROVIDE SOME FORMAL TRAINING TO DO THAT. IMPORTANTLY, WOULD FOCUS TEAMS MADE UP OF BASIC SCIENTISTS AND CLINICIANS. WE HAVE LOTS OF TRAINING PROGRAMS THAT HAVE BOTH PhDs AND CLINICIANS WORKING TOGETHER, BUT IN A SENSE THEY WORK ON THEIR OWN THINGS AND TALK TO EACH OTHER, THEY ARE NOT WORKING TOGETHER ON PROJECTS, FOR THE MOST PART. WHY AN INSTITUTIONAL PROGRAM? WHY DO YOU DO SOMETHING INSTITUTIONALLY OTHER INDIVIDUALLY? INSTITUTIONAL PROGRAMS CREATE THE ENVIRONMENT. THAT'S WHAT A T32 IS FOR. IT FUNDS A FEW INDIVIDUALS BUT WHAT IT DOES IS FORCES THE PROGRAMMATIC -- CREATION OF A PROGRAMMATIC EFFORT, AND CAN BE THOUGHTFUL AS OPPOSED TO BEING RANDOM, ONE INDIVIDUAL GOING INTO ONE LABORATORY AND YOU DO WHATEVER THAT LABORATORY MANDATES. YOU HAVE A GROUP OF PEOPLE THAT COME TOGETHER AND SAY HOW SHOULD WE BE TRAINING PEOPLE TO DO THIS SORT OF THING. WE ARE WORKING, IF YOU LOOK AT THE THIRD BULLET, WE ARE WORKING VERY HARD, TISCH WYGANT HAVE BEEN WORKING HARD FOR YEARS, PART OF SILBER BERG'S EFFORT TO BRING BACK STRONG TRAINING IN EXPERIMENTAL DESIGN STATISTICS, BRINGING RIGOR TO EXPERIMENTATION, WITH A PROGRAM, YOU'RE LEFT TO THE MERCY OF A LABORATORY ON AN INDIVIDUAL BASIS. THESE PROGRAMS WILL CREATE COHORTS OF TRAINEES THAT TALK TO EACH OTHER, COHORTS OF FACULTY THAT TALK TO EACH OTHER, TRAINEES TALK TO MULTIPLE FACULTY, IT REALLY BROADENS EVERYBODY'S EDUCATION AND TRAINING EXPERIENCE. AND RESEARCH. OF COURSE, IT CREATES COLLABORATIVE EFFORTS. IMPORTANTLY IT CREATES AN ACCOUNTABILITY, WHEN WE MAKE AN AWARD TO AN INDIVIDUAL WHAT HAPPENS, HAPPENS. MAYBE GOOD THINGS HAPPEN. MAYBE NOT GOOD THINGS HAPPEN. THERE'S NO CONTROL OVER IT. WHEN YOU HAVE AN INSTITUTIONAL PROGRAM, THERE'S AN ACCOUNTABILITY THAT THE P.I. AND THE LEADERSHIP OF THAT PROGRAM ARE RESPONSIBLE FOR MAKING GOOD THINGS HAPPEN. ALL RIGHT. SO NOW THAT'S THE GENERAL IDEA WHY WE WANT TO CREATE AN INSTITUTIONAL PROGRAM, WHY WE NEED THEM. AMIR IS GOING TO COME UP NOW AND TALK ABOUT THE SPECIFICS OF WHAT ARE WE TRYING TO ACCOMPLISH HERE. >> GOOD MORNING, EVERYONE. THANKS, STEVE. THIS HAS BEEN QUITE AN INTERESTING PATH OVER THE LAST SIX MONTHS THAT WE CROSSED. AND IF 2017 APPROVALS FOR PRODUCTS, THERAPEUTICS DEVICES, IS ANY INDICATION FOR WHAT'S COMING IN THE FUTURE, WE ARE REALLY ON A REALLY GREAT PATH. AND WHO KNEW THAT IN ONE YEAR YOU CAN HAVE A RECOMBINANT PROTEIN BEING APPROVED FOR BATTEN'S DISEASE, A DEVICE BEING APPROVED FOR CLUSTER HEADACHE, A HUMANIZED ANTIBODY BEING DEVELOPED FOR MULTIPLE SCLEROSIS, VARIOUS NUMBER OF SMALL MOLECULES BEING DEVELOPED FOR VARIOUS NEUROLOGICAL INDICATIONS, FREE RADICAL SCAVENGER COULD BE THE FIRST DRUG APPROVED NOW AND VARIOUS OTHER THINGS, OLIGO NUCLEOSIDES, SMA FOREFRONT, OLIGO NUCLEOSIDES ARE VIABLE PRODUCTS. SCRATCHING THE SURFACE, WE'RE NOW WORKING ON GENE THERAPY, GENE EDITING, EVERYTHING IS COMING TOGETHER, REALLY HOPEFULLY PROPELLING THE SCIENCE SO THAT BASIC RESEARCH CAN ACTUALLY HAVE THE APPROPRIATE TOOLS TO ADVANCE THESE PROJECTS, TO REAL PRODUCTS THAT COULD BE BENEFICIAL TO PATIENTS. SO IT'S A PERFECT STORM IN SOME WAYS. WE HAVE NUMBER OF TECHNOLOGIES THAT ARE NOW AVAILABLE, NUMBER OF PRODUCTS THAT CAN BE USED AS A GUIDING PRINCIPLES TO GET US THERE. AND THERE'S A GREAT EMPHASIS ON GOAL-DIRECTED RESEARCH NOW WITH THE EYE TO WHAT IS IT THAT'S GOING TO BE HELPING THE PATIENTS. IN FACT, THAT'S PART OF THE MISSION OF NINDS, TO BRING THERAPIES TO PATIENTS. SO WHAT ARE THE OPPORTUNITIES? AND WE FEEL THERE'S SORT OF FOUR-FOLD, ONE IS TO, AS STEVE SAID, CREATE THE ENVIRONMENT FOR PEOPLE TO DO BASIC RESEARCH. AND HAVE AN OPPORTUNITY WITHIN THAT ENVIRONMENT TO COLLABORATE. TO LEARN ABOUT WHAT IT WOULD BE LIKE TO ACTUALLY DEVELOP A PRODUCT, WHAT THE PATH LOOKS LIKE, AND INTERACT IN VARIOUS STAGES WITH INVESTIGATORS AND MENTORS, WHO HAVE BEEN PART OF THOSE TYPE OF ACTIVITIES AND DIRECTLY LEARN FROM THEM, HANDS ON, SO BY THE TIME THEY ARE READY TO GO IN A DIRECTION, THEY HAVE ALL THE CAPABILITIES AND SKILL SETS AND KNOW-HOW TO ACTUALLY EXECUTE. AND LASTLY, IT'S REALLY ABOUT STRIKING COLLABORATIONS AT THE TRAINING STAGE. AND HAVING THESE FOSTER OVER THE YEAR SO BY THE TIME THEY ARE READY FOR INITIATING THEIR OWN LABORATORIES, INITIATING THEIR OWN WORK IN INDUSTRY, THEY ARE REALLY IN A PLACE WHERE THEY CAN ACTUALLY PICK UP A PHONE AND TALK TO LOTS OF DIFFERENT PEOPLE AND BRAINSTORM AND TROUBLE SHOOT VARIOUS THINGS. SO IN SPECIFICALLY TRAINING OPPORTUNITIES ARE MANY-FOLD, ONE IS REALLY TO ESSENTIALLY LEARN THAT IT DOES TAKE MORE THAN JUST ONE LABORATORY TO DEVELOP A PRODUCT. THERE ARE MANY CONSIDERATIONS THAT COME IN PLAY, ALL THE WAY TO COMMERCALIZATION, WHICH HOPEFULLY IT'S SOMETHING THAT INDUSTRY CAN REALLY CHAMPION. BUT THERE ARE MANY, MANY STEPS THAT COME IN PLAY, INCLUDING JUST GOING OVER TO THE OFFICE OF TECHNOLOGY DEVELOPMENT AND TALKING TO THE PATENT OFFICER TO SEE IF THIS IDEA CAN ACTUALLY HAVE ANY LEGS FOR PATENTABILITY. LEARN ABOUT SPECIFIC AREAS, ADVANCING BASIC, AND THERE'S MANY CHALLENGES AS YOU ALL WERE FAMILIAR WITH ON HOW DO YOU ACTUALLY GET FROM PRE-CLINICAL STAGE TO CLINICAL STAGE. INTERACT WITH MENTORS WHO HAVE THE EXPERIENCE, AND FINALLY COLLABORATE WITH PEOPLE THAT ARE WITHIN FDA, NON-PROFITS, EVEN WITHIN DIFFERENT INSTITUTES TO LEARN ABOUT MISTAKES THEY HAVE DONE, TO GET GUIDING PRINCIPLES, LEARN ABOUT GUIDANCE DOCUMENTS THAT ARE READILY AVAILABLE FOR THEM TO LEARN ABOUT HOW TO DEVELOP A NON-OPIOID PAIN MEDICINE THAT'S A GUIDANCE DOCUMENT PUBLISHED IN 2014 BY THE FDA JUST TO LEARN ABOUT THESE THINGS ARE OUT THERE AND HOW WE CAN ACCOMPLISH THEM. SO WHAT ARE THE FEATURES? AND REALLY IT'S ABOUT GETTING JUST LIKE STEVE SAID A FOCUSED TRAINING THAT'S ALL ABOUT EXPOSURE, TO VARIOUS STAGES, BUT REALLY TOWARDS THE END PRODUCTS THAT ARE REALLY HOPEFULLY BENEFITING THE PATIENTS. CROSS DISCIPLINE TRAINING, STUDENTS CAN HAVE AN OPPORTUNITY TO GO AND WORK WITHIN THE BIOTECH OR PHARMACEUTICAL ENVIRONMENT OR ANY OTHER ENVIRONMENT THAT ACTUALLY IS ANSWERING BIG QUESTIONS AND LEARN FIRST LAND WHAT IT WOULD TAKE, THE TYPE OF LANGUAGES REQUIRED TO COMMUNICATE THESE TYPE OF THINGS. WE HAVE A VERY ACTIVE R25 PROGRAM THAT MEETS ONCE A YEAR AND TRAINS STUDENTS FOR VARIOUS ACTIVITIES, SMALL MOLECULES, BIOLOGICS AND SO ON. WE'D LIKE TO SEE INSTITUTIONS THAT ACTIVELY PURSUE THESE TIMES OF DIDACTIC TRAINING AND TEACH VARIOUS TOPICS THAT ARE REALLY IMPORTANT. FINALLY TO SORT OF LEARN ABOUT COMMUNICATION SKILLS, WHAT DOES IT TAKE TO MAKE AN ELEVATOR PITCH, HOW DO YOU GO OUT AND RAISE ADDITIONAL FUNDS FROM NON-CONVENTIONAL TYPE SOURCES? HOW DO YOU GO TO A VC FUND, TO PHARMACEUTICALS AND TALK ABOUT YOUR IDEAS, HOW YOU CAN PERHAPS STRIKE COLLABORATION, ALL THESE THINGS COME TOGETHER AS PART OF HAVING THIS PROGRAM. SO THIS HAS BEEN A REALLY INTERESTING EXPERIENCE FOR STEVE AND I AND THE LARGER GROUP. I WANT TO MAKE SURE WE THANK ALL OF THEM. KARI, CHUCK, STEPHANIE, NICK AND A NUMBER OF OTHER PEOPLE HAVE REALLY CONTRIBUTED TO THIS. THE PEOPLE THAT REALLY HAVE DONE THE HEAVY LIFTING TO DO HOURS AND HOURS OF RESEARCH AND SORT OF OUT DATA FOR US HAS BEEN CHRISTINA AND TISCH, WE WANT TO THANK THEM FOR THEIR EFFORTS, AND THANK YOU. >> QUESTIONS? BEV, STEVE AND LARRY. >> THIS IS REALLY GREAT. SOME INSTITUTIONS DO THIS UNDER THE GUISE OF CTSA OR MAYBE NOT FOCUSED IN NEUROSCIENCE BUT IN OTHER, YOU KNOW, IN OTHER CLINICAL AREAS WHERE THEY ARE BRIDGING BASIC AND CLINICAL RESEARCHERS. CAN YOU ANSWER THE ONE INSTITUTION THAT WAS ONE OUT OF 289 OR WHATEVER THAT WAS? >> YEAH, WE CAN DO THAT FUNDED, LESLIE THOMPSON HAS A T32 AT IRVINE, STEM CELL PROGRAM, WHERE THEY HAVE STUDENTS DOING BASIC RESEARCH ON STEM CELL PROPERTIES. THEY HAVE STUDENTS WORKING WITH CLINICIANS TO INJECT STEM CELLS INTO PEOPLE. THEY HAVE HAD A COUPLE PEOPLE GO INTO INTERNSHIPS WITH LOCAL STARTUPS AND THEN COME BACK AND CONTINUE THEIR RESEARCH. WE'VE LEARNED A LOT FROM THEM. THEY IN FACT DO -- STARTED VIDEO SHARK TANK PITCHES, AND REALLY WHAT IT'S ABOUT, IT'S NOT SO MUCH LEARNING HOW TO RAISE MONEY AS LEARNING HOW -- IT HELPS THE STUDENTS FIGURE OUT THE SIGNIFICANCE OF WHAT THEY ARE DOING AND WHAT ARE THE SHORTFALLS. THERE'S ALL THESE KINDS OF PROFESSIONAL ITEMS. YEAH. >> YEAH, I ALSO FEEL REALLY GOOD ABOUT THIS, HAVE A LOT OF SUPPORT FOR THIS CONCEPT. SO MY QUESTION WAS YOU'VE THOUGHT ABOUT A LOT OF POTENTIAL THINGS THAT COULD BE INCLUDED IN THESE. BUT WHAT DO YOU CONSIDER THE BASIC REQUIREMENTS THAT, YOU KNOW, OF ALL THE POSSIBILITIES TO INCLUDE, SAY INDUSTRY RELATIONSHIPS, REGULATORY CONNECTIONS, ALL OF THAT, WHAT DO YOU CONSIDER THE BASIC REQUIREMENTS AS OPPOSED TO OPTIONS? >> WE MAY HAVE TO TAG TEAM THIS ANSWER. ONE OF THE THINGS THAT MAKES THIS JOINT EFFORT REALLY ENJOYABLE IS THAT WE HAVE SUCH DIFFERENT PERSPECTIVES THAT WE THINK IN DIFFERENT WORLDS. THE NUMBER ONE THING IS THAT EVERY TRAINEE HAS TO BE DOING A GREAT RESEARCH PROJECT. JUST LIKE EVERYBODY ELSE, IT CAN'T BE -- THIS IS NOT ABOUT ACTUALLY DOING THE PRE-CLINICAL TRANSLATIONAL WORK. IT'S ABOUT DOING A BASIC RESEARCH PROJECT WELL AND UNDERSTANDING HYPOTHESIS TESTING AND UNDERSTANDING HOW TO BE A SCIENTIST. THAT'S THE NUMBER ONE REQUIREMENT. BRINGING TEAMS OF PEOPLE TOGETHER IS ANOTHER REQUIREMENT. THIS HAS TO INVOLVE BOTH BASIC SCIENTISTS AND CLINICIANS, AND PEOPLE WHO KNOW HOW TO DO TRANSLATIONAL WORK. AND SO FROM MY POINT OF VIEW ALL THE THINGS THAT MAKE A GREAT PROGRAM ARE A REQUIREMENT. THERE ARE SPECIFICS THAT AMIR MIGHT WANT TO SPEAK TO ABOUT WHAT MAKES THIS DIFFERENT FROM OTHERS. >> IT REALLY IS ABOUT RESEARCH. AND SOME INSTITUTES ARE REALLY IN A PERFECT POSITION TO COME OUT OF THIS, RIGHT? SO YOU CAN IMAGINE INSTITUTES THAT HAVE A VERY ACTIVE TECH TRANSFER OFFICE, THEY HAVE MBA PROGRAMS FOR ENTREPRENEURSHIP, WHO THEN CAN TEAM UP WITH THE STUDENTS TO LEARN ABOUT WHAT IT WOULD REALLY TAKE TO ACTUALLY GO TO NEXT STEP. THERE ARE ENGINEERING PROGRAMS THAT COULD BE TEAMED UP WITH. THERE'S SO MANY OPPORTUNITIES. WE DON'T WANT TO BE PRESCRIPTIVE ABOUT THIS. WE WANT TO JUST LAY OUT SOME IDEAS AND ASK FOR PEOPLE TO REALLY COME UP WITH WHAT WOULD WORK BEST FOR THEM, HOW DO THEY POOL RESOURCES WITHIN INSTITUTES AND COME UP WITH A PROPOSAL. >> THIS SEEMS LIKE A MARVELOUS IDEA. ONE OF THE THINGS THAT STRUCK ME AS YOU WERE GOING THROUGH THIS WAS POTENTIAL PERHAPS TO DEVICE SOME TYPE OF PARTNERSHIP WITH PHARMA OR BIOTECH. TO GET SOME BUY-IN, MONEY TO HELP SUPPORT THIS KIND OF PROGRAM, THEY WILL BE THE MAJOR BENEFICIARIES OF THIS KIND OF TRAINING. >> GREAT POINT. >> SIMPLE QUESTION, WILL THIS GO INTO THE CATEGORY OF CLINICAL TRIALS REQUIRED, CLINICAL TRIALS DISALLOWED? I'M NOT ACTUALLY JOKING. I'M TRYING TO UNDERSTAND HOW THIS WOULD FIT TOGETHER. >> THIS WILL BE CLINICAL TRIALS DON'T EXIST. YEAH, THERE WILL BE NO CLINICAL TRIALS HERE. >> THIS WON'T HAVE HUMAN SUBJECTS RESEARCH. >> NO. >> EVEN THOUGH THIS IS PRE-TRANSLATIONAL. OKAY. >> DO YOU FORESEE THIS BEING DISEASE FOCUSED OR BRIDGING ACROSS A NUMBER OF NEUROLOGIC DISEASES TAKING ADVANTAGE OF INSTITUTIONAL INFRASTRUCTURE? >> IT COULD BE BOTH, DEPENDING HOW YOU WANT TO TAILOR AND DEPENDING WHAT MENTORS, WHO ARE THE MENTORS THAT ARE COMING TOGETHER TO DO THIS. IDEALLY, IT'S BENCH SCIENCE, AND WITH THE IDEA THAT YOU CAN EITHER GO AFTER ONE SPECIFIC DISEASE AREA OR YOU CAN FIND COMMONALITIES AND MECHANISMAL ACTIONS THAT GO BEYOND THAT, DEPENDS ON THE FIELD OF RESEARCH YOU WANT TO PURSUE AND WE'RE CERTAINLY OPEN FOR THAT AS LONG AS THEY ARE IN THE MISSION OF NINDS. >> IF I COULD ADD ONE THING BEFORE WE ASK YOUR NEXT QUESTION. WE TRY VERY HARD NOT TO TELL PEOPLE WHAT THEY SHOULD BE DOING, WHAT WE WANT THEM TO DO IS COME IN WITH THEIR STRENGTH THAT ACCOMPLISHES A MISSION THAT WE'RE TRYING TO ACCOMPLISH. >> JUST SOME FOLLOW-UP TO THE QUESTION, WHY NOT INCLUDE CLINICAL TRIALS SINCE YOU WANT TO TRAIN BASIC SCIENTISTS IN PURSUING THAT TRANSLATIONAL LINK? YOU WANT TO TEACH THEM RESEARCH METHODOLOGY, CLINICAL RESEARCH METHODOLOGY, EVEN LEADING UP TO TRIAL DESIGNS. >> YOU KNOW, WE CAN THINK ABOUT THAT. I THINK WHAT WE TRY TO BE CAREFUL OF IN SOMETHING LIKE THIS IS NOT TO BE ALL THINGS TO ALL PEOPLE, AND TRY TO NARROW DOWN A FOCUS OF A MISSION. A MISSION KIND OF FOCUS TO SOMETHING THAT PEOPLE JUST AREN'T ALL OVER THE MAP. AND I THINK FOR THIS, AND LET ME JUST SAY THIS DOES NOT PRECLUDE ANYBODY COMING IN FOR ANYTHING. THERE'S A REGULAR T32 FOA, PEOPLE CAN PROPOSE TO DO WHATEVER, INCLUDING THIS. THEY COULD BE DOING THIS WITH THE REGULAR FOA, THEY JUST AREN'T. AND WE'RE TRYING TO STIMULATE A SPECIFIC ACTIVITY. >> DAVID? >> I WONDER IF YOU COULD COMMENT ON THE RESOURCES THAT MIGHT BE AVAILABLE IN ADDITION TO THE STANDARD RESOURCES THAT ARE AVAILABLE IN THE T32 TO PROMOTE THESE KINDS OF BOOT CAMPS AND SYMPOSIA NOT TYPICALLY PART OF A T32 STRUCTURE AND THE SECOND QUESTION, MORE PRACTICAL, WHEN IS YOUR TIME LINE FOR LAUNCH? >> THAT'S A VERY ENCOURAGING STATEMENT. THANK YOU. WHAT WE OFTEN -- SO T32s, THE FUNDING THAT WE COULD PROVIDE IN THE T32 IS REGULATED AND MANDATED AND RESTRICTED AND WE'RE NOT IN CONTROL OF IT. WHAT WE DO THOUGH, AMIR ALLUDED TO THIS, WE'LL OFTEN RUN R25 PROGRAMS THAT THEN CAN LINK UP AND BRING THESE T32 PROGRAMS TOGETHER TO DO SOMETHING GREATER. WE CAN PROVIDE SUPPLEMENTS FOR SPECIFIC ACTIVITIES. BUT WE CAN'T -- FOR EXAMPLE WE WOULD NOT BE ALLOWED TO PUT RESEARCH DOLLARS INTO A T32 OR ANYTHING LIKE THAT. p>> ANY OTHER QUESTIONS? OKAY. THEN WE NEED A MOTION TO ALLOW OR NOT ALLOW THIS CONCEPT TO MOVE FORWARD. SECOND. ALL IN FAVOR OF MOVING THIS FORWARD, HOLD YOUR HANDS UP IF YOU'RE -- OH, RIGHT. YOU'RE AD HOC, OKAY. ALL OPPOSED? ABSTENTIONS? OKAY. OH, I'M SORRY, TIM, WHAT DO YOU THINK OF THIS CONCEPT, ARE YOU VOTING FOR IT OR AGAINST IT? >> I'M FOR IT. I'M SORRY, THE FILM HAS BEEN CUTTING IN AND OUT BUT I'M VERY SUPPORTIVE. IT'S A GOOD IDEA. >> THANKS A LOT. THANKS, STEVE. THANKS, AMIR. STEVE ACTUALLY STAYS UP THERE BECAUSE THE NEXT INITIATIVE CONCEPT INVOLVES PROMOTING FACULTY HIRING SPECIFICALLY FOR WOMEN AND UNDERREPRESENTED GROUPS. SO STEVE AND MICHELLE JONES-LONDON ARE GOING TO TALK ABOUT THIS. >> OKAY. SO THIS IS ANOTHER ONE WE'RE VERY EXCITED ABOUT. I'VE BEEN WORKING WITH MICHELLE FOR YEARS NOW ON TRYING TO ENHANCE DIVERSITY AND REALLY ENHANCE THE IN-- INCREASE THE NUMBER OF WOMEN IN LEADERSHIP POSITIONS WITH THE T32s FOR ME AND MICHELLE HAS HER PROGRAMS FOR PROMOTING DIVERSITY, AND THIS IS ANOTHER PROGRAM THAT WE ARE KIND OF EXCITED ABOUT. SO THIS IS -- I WANT TO SAY THIS IS GOING TO BE AN OPPORTUNITY FOR WOMEN AND UNDERREPRESENTED GROUPS AND SO THIS INCLUDES, YOU KNOW, UNDERREPRESENTATIVE MINORITIES AND PEOPLE WITH DISABILITIES, AND WOMEN AND IT'S DIVERSITY WRIT LARGE IS WHAT WE'RE TALKING ABOUT. WHEN YOU SEE DIVERSITY, IT'S ALL OF THESE GROUPS. AND SO JUST A POINT TO MAKE ABOUT WHY WE WOULD DO SUCH A THING, THIS IS SfN DATA FROM 2017. YOU CAN SEE THERE'S A BIG DROP-OFF IN THE NUMBER OF WOMEN WHEN YOU GO FROM POSTDOCS TO FACULTY. AND THE SAME FOR MINORITIES. LET ME JUST SAY THIS MINORITY DATA FROM SFN INCLUDES ASIANS. ALL OF THESE NUMBERS DROP TO MUCH SMALLER THAN WHAT'S ON HERE BUT THAT'S THE DATA THAT I HAD. BUT REGARDLESS, THERE'S A BIG DROP-OFF WHEN YOU GET TO FACULTY. AND WHAT WE HAVE, I WANT TO SAY WE'RE GOING TO PROPOSE SOMETHING HERE THAT DOES NOT IN ANY WAY ADDRESS WHY, RIGHT? THERE ARE PROBABLY DOZENS OF REASONS WHY THESE THINGS ARE TRUE. AND WE'RE NOT TARGETING ANY PROPOSED REASON. WE'RE JUST GOING TO TRY TO CHANGE THINGS. AND SO THE GOAL, THERE WERE TWO GOALS OF THIS INITIATIVE. ONE IS THAT IS IMMEDIATE HIRING. WE'RE GOING TO USE A P30, I'LL TALK TO YOU IN A MINUTE, BASICALLY PROVIDES MONEY TO INSTITUTIONS TO HIRE WOMEN AND MINORITIES AND PEOPLE WITH DISABILITIES INTO TENURE-TRACK OR EQUIVALENT POSITIONS. IT WILL ATTEMPT TO CREATE AN ENVIRONMENT FOR SUCCESS OF THESE INDIVIDUAL HIRES. ONCE YOU HIRE THEM, YOU NEED TO RETAIN THEM. THEY NEED TO BE SUCCESSFUL. AND THIS MECHANISM IS INTENDED TO CREATE THAT. IT WILL -- IT IS GOING TO BE DESIGNED TO HAVE A LONG-TERM EFFECT. THERE'S AN IMMEDIATE EFFECT, WE PROVIDE MONEY, PEOPLE GET HIRED, BUT OBVIOUSLY THAT'S LIMITED. WE'RE NOT GOING TO CHANGE THE WORLD WITH A HANDFUL OF HIRES. AND THE GOAL IS TO HAVE A LONG LASTING INFLUENCE. AND THE OTHER THING IN FACT, THIS MAY BE EVERYBODY, YOU KNOW, WHEN YOU TALK ABOUT TRAINING IT'S VERY HARD TO KNOW WHETHER ANY PARTICULAR THING THAT YOU DO IN TRAINING IS A CAUSAL INFLUENCE ON THE RESULTS. AND THIS IS A CASE WHERE I THINK WE ACTUALLY HAVE AN EXPERIMENT WE CAN DO. AND WE ARE GOING TO TEST THE HYPOTHESIS THAT THE APPROACH WE'RE PROPOSING TODAY WILL HAVE AN IMPACT EVEN ON THE INSTITUTIONS THAT DO NOT RECEIVE MONEY. AND THAT'S A PRETTY RARE EXPERIMENT TO BE ABLE TO DO. SO WHAT'S THE APPROACH? THIS IS JUST FOR ALL OF YOU, SOME OF YOU REMEMBER, SOME OF YOU PROBABLY DON'T, BACK THE ARA DAYS IN 2009, 2010, ONE OF THE THINGS THAT NIH DID IS IT CREATED THIS P30 MECHANISM TO PROVIDE MONEY TO INSTITUTIONS TO HIRE PEOPLE INTO TENURE TRACK POSITIONS. THIS IS REALLY MIRRORING THAT APPROACH. IT WOULD BE A FIVE-YEAR AWARD. WE ARE PROPOSING TO REQUIRE EACH INSTITUTION THAT IS SUCCESSFUL TO HIRE TWO TO THREE PEOPLE INTO A SINGLE ORGANIZATIONAL UNIT. WE WOULD PREFER THREE, BUT REALLY WE UNDERSTAND THE REALITY THAT PLACES MAY NOT BE ABLE TO ACTUALLY CREATE THREE POSITIONS IN A SINGLE ORGANIZATION UNIT. BUT THERE CAN'T JUST BE A SINGLE PERSON. THERE WILL BE A STRUCTURED MENTORSHIP PROGRAM THAT WOULD BE CREATED FOR THESE, THIS GROUP OF HIRES, BUT ONCE YOU CREATE THAT IT CAN BE USED FOR ALL HIRES. AND REALLY ANYBODY. THE INSTITUTION WILL HAVE TO HAVE SKIN IN THE GAME. IF WE JUST PROVIDE MONEY FOR SOMETHING WHEN THE MONEY RUNS OUT IT CAN END. INSTITUTIONAL COMMITMENT, THEN THINGS LAST A LOT LONGER. SO THEY WILL HAVE TO GUARANTEE A FIVE-YEAR SALARY, P30 WOULD PROVIDE PART OF IT. THEY WOULD HAVE TO PROVIDE THE FULL START-UP APPROPRIATE FOR THAT POSITION, THAT VARIES BY INSTITUTION AND POSITION, BUT WHATEVER IS NORMAL THEY WILL HAVE TO GIVE, THE P30 WILL PROVIDE PART OF THAT. IT WILL BE SPREAD OVER A FIVE-YEAR PERIOD. AS AN EXAMPLE OF SUCCESS NINDS P30 WE RAN, THERE WERE 28 HIRES AND I'M ONLY TALKING ABOUT 26, JUST SO YOU KNOW WHY THERE WERE A COUPLE OF HIRES THAT WERE NEUROSCIENTISTS HIRED INTO THE SAME DEPARTMENT THAT HAD THE SAME NAME, AND SO I DIDN'T KNOW WHICH ONE WAS WHICH SO I DIDN'T KNOW HOW TO EVALUATE THEM. I'M TALKING ABOUT 26 OF THEM. THEY ALL ARE STILL IN TENURE TRACK POSITIONS HIRED IN 2009, 2010. 85% ARE R01s OR TP2s. TWO OF THE 26 THAT DID NOT EVER GET AN R01 EQUIVALENT HAVE BEEN PROMOTED TO ASSOCIATE PROFESSOR, SO CLEARLY THEY DID SOMETHING RIGHT. TWO OTHERS ARE STILL IN THEIR POSITIONS, THEY HAVE OTHER KINDS OF FUNDING, NOT R01 OR DP2. IF YOU DO IT RIGHT THIS CAN BE ENORMOUSLY SUCCESSFUL. THE KEY IS HAVING JUST MAKING SURE THE INSTITUTIONS ARE COMMITTED FINANCIALLY AND OTHERWISE. I THINK THIS IS MY LAST SLIDE. AND LEADS INTO WHAT MICHELLE IS GOING TO TALK ABOUT AS TO WHY WE THINK THIS WILL HAVE BROADER IMPACT. IT WILL REQUIRE, FIRST OF ALL, REQUIRE A PLAN FOR MENTORING AND FOSTERING SUCCESS OF THESE INDIVIDUALS AND ONCE THEY CREATE THAT AGAIN FOR THESE INDIVIDUALS IT WILL APPLY TO EVERYBODY BECAUSE WHY NOT? IN ORDER TO APPLY AND BE SUCCESSFUL THEY ARE GOING TO HAVE TO COME UP WITH A DETAILED ACCOUNTING OF WHERE THEY ARE, AND WHAT THEY HAVE DONE SO FAR. AND A PLAN FOR WHAT THEY ARE GOING TO DO IN THE FUTURE. AND WE THINK THIS IS A REALLY IMPORTANT PART OF THIS FOA, AND MICHELLE IS GOING TO EXPLAIN WHY. AND SO HERE IS WHERE MICHELLE COMES IN. >> GOOD MORNING, EVERYONE. AND SO WHAT I'LL TALK ABOUT IS THE VISION FOR THE LONG-TERM OUTCOMES, REALIZING THAT WHAT I'M GOING TO SPEAK ABOUT ISN'T GOING TO BE IMMEDIATE, THIS ISN'T SOMETHING THAT'S GOING TO HAPPEN IN THE FIRST YEAR, MAYBE EVEN THE SECOND YEAR. IT REALLY TAKES INTO ACCOUNT WHAT I FEEL IS THE SHIFT IN THE MOVEMENT OF HOW WE'RE THINKING ABOUT INCLUSION AND DIVERSITY, ESPECIALLY FOR WOMEN AND MINORITIES. I THINK THE OLD THOUGHT PATTERNS OF FIXING PEOPLE TO MAKE THEM BETTER, TO BE MORE COMPETITIVE, IS REALLY CHANGED INTO THINKING ABOUT WHAT ARE THE INSTITUTIONAL STRUCTURES THAT THESE PEOPLE ARE GOING INTO, AND THE FACT THAT SOMETIMES THESE STRUCTURES COULD BE BROKEN, AND HOW DO WE INFLUENCE THE INSTITUTIONAL STRUCTURE AND THE CLIMATE AND THE ENVIRONMENT THAT PEOPLE ARE GOING INTO. AND SO WITH THIS P30 WE REALLY EXPECT THIS INVESTMENT OF, YOU KNOW, UP TO THREE HIRES TO HAVE A RIPPLE EFFECT BEYOND THOSE JUST THREE INDIVIDUALS. WITH THE FIRST THING BEING REALLY INFLUENCING HIRING PRACTICES ACROSS THE INSTITUTION, RIGHT? SO WE'RE TARGETING A NEUROSCIENCE ORGANIZATIONAL UNIT AT OUR DEPARTMENT. BUT OF COURSE ONCE PEOPLE SEE HOW THIS CAN BE DONE, OUR THEORY AND HOPE IS THIS WILL SPREAD ACROSS THE INSTITUTION ITSELF. THE OTHER THING IS INFLUENCING INSTITUTIONAL CLIMATE AND CULTURAL AWARENESS, RIGHT? BUT ONCE AGAIN THE SHEER ACT OF PUTTING THIS TOGETHER AND PAYING ATTENTION TO DIVERSITY AND INCLUSION CREATE A BETTER AWARENESS. THE THIRD THING, AND THIS IS BORNE OUT BY OTHER NSF ACTIVITIES, HHMI, WHEN YOU ACTUALLY MAKE DIVERSITY GOALS EXPLICIT AND WRITE DOWN STRATEGIES TO ACHIEVE THOSE GOALS, YOU CAN MAKE BETTER PROGRESS. THAT SOUNDS LIKE A NO-BRAINER, AS SCIENTISTS, BUT WHEN IT COMES TO DIVERSITY SOMETIMES IT'S GOOD INTENTIONS, PERHAPS REALLY NICE CONVERSATIONS AROUND IT, A FEW SPEAKER SERIES, BUT NO REAL EXPLICIT IN BLACK AND WHITE ACTION PLANS OR GOALS. HOPEFULLY THE P30 WILL GIVE THAT THE STRUCTURE THAT WE NEED TO ACTUALLY ACHIEVE THE OUTCOMES. AND THE LAST BULLET, SORT OF TOUCHES ON WHAT STEVE ALREADY MENTIONED, IS THAT WHEN A GROUP OF PEOPLE GET TOGETHER AND SET OUT TO WRITE ANY INSTITUTIONAL, WHETHER A P30, P50, ANY BIG PROGRAM, YOU START TO GET AND GENERATE IDEAS AND CONVERSATIONS, THAT PERHAPS WEREN'T ALREADY HAPPENING. AND ONCE YOU KNOW BETTER, YOU TEND TO DO BETTER, RIGHT? SO THE MERE ACT OF PUTTING THIS APPLICATION TOGETHER, GETTING BUY-IN FROM DEPARTMENT HEADS AND CHAIRS AND HAVING THIS CONVERSATION, WE HOPE WILL IMPROVE AND POTENTIALLY INFLUENCE HOW PEOPLE FEEL ABOUT DIVERSITY WITHIN THEIR INSTITUTION. AND THAT'S PUTTING THE APPLICATION IN. OF COURSE, GETTING THE MONEY WOULD BE EVEN BETTER, BUT ONCE AGAIN WE'VE SEEN FROM OTHER PROGRAMS LIKE ADVANCE THAT NSF FUNDS TO TARGET INCREASING WOMEN IN S.T.E.M. IS THAT SOMETIMES DEPARTMENTS, INSTITUTIONS BY THE MERE FACT OF SITTING DOWN AND ACTUALLY TAKING A STEP AWAY TO LOOK AT THIS PROBLEM IN A CONCENTRATED EFFORT CAN IMPROVE THE OUTCOMES. AND SO THAT WILL BE SORT OF OUR CONTROL GROUP. SO WE'LL HAVE P30s THAT NOT EVERYBODY THAT APPLIES OBVIOUSLY WILL BE ABLE TO GET THE AWARD, WE'LL HAVE P30s THAT ACTUALLY SUBMIT THE APPLICATION, AND DON'T GET FUNDED VERSUS THE P30s THAT ARE AWARDED. WE'LL BE ABLE TO LOOK BACK AND SEE IF THIS THEORY HOLDS TRUE. IN TERMS OF THE DOWNSTREAM BENEFITS TO THE RESEARCH ENVIRONMENT, THE THOUGHT WITH HAVING THIS NOT BE JUST, YOU KNOW, ONE PERSON COMES IN OR INDIVIDUAL AWARD IS THE BENEFIT THAT ONCE AGAIN WE KNOW FROM LITERATURE, FROM UNIVERSITIES THAT DO CLUSTER HIRING OR PROGRAMS THAT HAVE DONE COHORT HIRING THAT YOU ALSO GET THESE OTHER DOWNSTREAM BENEFITS. IN TERMS OF THE COHORT HIRING, WE WOULD EXPECT TO SEE A HEIGHTENED POTENTIAL FOR COLLABORATION, HOPEFULLY A SUPPORT OF TEAM SCIENCE, ESPECIALLY WITH THE DEMOGRAPHICS OF THIS GROUP THAT TEND TO COLLABORATE MORE. IN TERMS FOR THE INDIVIDUALS THEMSELVES, THEY WON'T NECESSARILY BE AN n-OF-1 IN TERMS OF, YOU KNOW, IDENTIFYING WITHIN THE DIVERSITY CATEGORY, SO YOU COULD HAVE THE POTENTIAL FOR SUPPORT SYSTEM. AND THEN ALSO CRITICAL MASS OF INFLUENCE, I THINK THAT WE KNOW AND WE'VE SEEN A LOT OF CONVERSATIONS ABOUT THE AMPLIFICATION EFFECT, IF YOU HAVE WITHIN A GROUP OR COMMITTEE ONE WOMAN SAYING SOMETHING, IT SOMETIMES GETS DROWNED OUT OR SOMEONE ELSE TAKES CREDIT FOR THE ACTUAL COMMENT BUT BY HAVING A GROUP OR COHORT, YOU HAVE MORE OF THIS VOTING EN BLOC POWER, HOPEFULLY THE P30 CAN PROVIDE THAT CRITICAL MASS OF INFLUENCE AS WELL. IN TERMS OF HIRING A DIVERSE FACULTY ACTUALLY GIVES TO THAT DEPARTMENT, THE INSTITUTION ITSELF, IS REALLY A POSITIVE ENVIRONMENT FOR ALL TRAINEES. AND SPECIFICALLY, WE THINK ONCE AGAIN THERE ARE STUDIES TO SHOW THIS THAT HAVING DIVERSE FACULTY CAN HELP TO INCREASE NOT ONLY THE EXPOSURE FOR ROLE MODELS, FOR THE EXISTING TRAINEES, BUT CAN ACTUALLY HELP INCREASE RECRUITMENT OF NEW STUDENTS. BUT JUST THE FACT OF HAVING DIVERSE FACULTY REALLY TRANSLATES TO A BENEFIT FOR ALL TRAINEES AND ALL STUDENTS. THE THIRD IS THAT STEVE MENTIONED THIS, THE DEVELOPMENT OF THIS REALLY STRUCTURED MENTORING PROGRAM, JUNIOR FACULTY APPROPRIATE INPUTS IN COACHING AND SPONSORSHIP, IT WILL BE NECESSARY TO COME IN FOR THE P30 TO HAVE THAT STRUCTURE THERE, BUT OF COURSE YOU'RE NOT GOING TO BUILD THAT JUST FOR THE THREE PEOPLE. ONCE WE ENVISION THAT ONCE THE DEPARTMENT OR INSTITUTION MAKES THAT INVESTMENT, THAT WILL HELP ALL BOATS TO RISE AS WELL. OTHER JUNIOR FACULTY WILL PROBABLY TAKE ADVANTAGE OF THIS, YOU KNOW, MENTORING AND CAREER DEVELOPMENT RESOURCES THAT WILL HAVE TO BE PUT TOGETHER FOR THE P30 FACULTY. AND THIS IS MY LAST SLIDE. YOU KNOW, THIS REALLY FOCUSES ON HOW WE WILL LOOK AT -- HOW WILL WE KNOW THIS INVESTMENT MADE A DIFFERENCE? DID IT CHANGE ANYTHING? DID IT MATTER? I'VE ALREADY TOUCHED ON THE THREE LEVELS THAT WE'LL LOOK AT BUT I'LL GO OVER IT AGAIN. WE'RE GOING TO LOOK AT THE INSTITUTION, AT THE INDIVIDUAL FACULTY, BUT THEN ALSO THE TRAINEE POPULATION. IN TERMS OF WHEN THE APPLICATION COMES IN, WE'LL REQUEST THIS BEFORE DATA IN TERMS OF DEMOGRAPHICS, ALSO INSTITUTIONAL CLIMATE, AND THEN WE'LL BE ABLE TO LOOK AT THE BEFORE AND THE AFTER FOR THE P30. IN TERMS OF INDIVIDUAL FACULTY, THAT WILL BE THE NORMAL METRICS THAT YOU WOULD MEASURE IN TERMS OF GRANTS, PUBLICATIONS, PROMOTION AND RETENTION. AND THEN FOR THE TRAINEE POPULATION, DOES YOUR THEORY HOLD TRUE, DO WE SEE DIFFERENCES IN DIVERSE TRAINING RERUT. RECRUITMENT AND RETENTION. THAT IS IT. STEVE AND I WILL TAKE QUESTIONS. >> LARRY AND THEN GORD, DAVID AND AMY. REMEMBER THAT ORDER. >> I THINK THIS IDEA OF HIRING A GROUP IS A GREAT IDEA BUT IN THAT VEIN IS THIS RESTRICTED TO ONLY FIRST-TIME FACULTY PEOPLE OR WOULD IT BE POSSIBLE FOR THREE PEOPLE TO HAVE A RANGE OF EXPERIENCE, MAYBE ONE HAS AT LEAST A FEW YEARS OF FACULTY EXPERIENCE? >> GREAT QUESTION. IN OUR MIND WE'VE BEEN THINKING ABOUT JUNIOR FACULTY. WE HADN'T THOUGHT ABOUT HAVING THE RANGE OF EXPERIENCES. >> I THINK WHAT WE ALWAYS THINK ABOUT, AND WE ARE NOT STUCK ON ONE WAY OR ANOTHER RIGHT AT THIS POINT, IT'S A GREAT POINT. IF YOU HAVE A PROGRAM WHERE YOU HIRE A FACULTY MEMBER WHO IS ALREADY A FACULTY MEMBER, YOU AREN'T CHANGING THE NUMBER OF FACULTY MEMBERS. AND THAT'S I THINK LARGELY WHY WE THINK IN TERMS OF NEW PEOPLE COMING IN. I UNDERSTAND. THEY GO FROM BEING A FACULTY MEMBER AT ONE PLACE TO A FACULTY MEMBER AT ANOTHER PLACE. >> WE'RE GETTING COMPLAINTS ON THE PHONE WE'RE GOING IN AND OUT. USE YOUR MICROPHONES AND TRY TO STAY CLOSE TO YOUR MICRO PHONE. >> SO I WANT TO MAKE A COUPLE POINTS, ONE OF WHICH IS THIS IS AN INTERESTING CONTRAST TO THE K99 PROGRAM. I HAD A REAL BEEF WITH SOME OF THE IMPLICATIONS -- THE WAY K99S WERE USED BY UNIVERSITIES, PROBABLY THE ONE I OBJECTED TO, SfNs, PEOPLE WHO RECEIVE K99s IN NOT KNOW SUBTLE WAY SAYING THEY ARE GOING TO DEFER RECRUITMENT COST THROUGH K99 RECRUITMENT, THIS IS MUCH BETTER. A COUPLE SUGGESTIONS THE WAY YOU MIGHT IMPLEMENT THIS, P30 IS A NICE NUMBER. I HAVE NOTHING AGAINST THE ACTUAL NOMENCLATURE. IT'S ENTIRELY UNINSPIRING. I THINK THAT FRANKLY IF YOU'RE GOING TO DO SOMETHING LIKE THIS YOU NEED TO CREATE AN ESPIRIT DE CORPS, PUT MONEY INTO CACHET, MEETINGS FOR INDIVIDUALS HIRED THIS OF THROUGH THIS PROGRAM, LIKE McKNIGHT MEETING WHERE THEY CAN FEEL PROUD AND BROAD TOGETHER, NOT RESTRICTED TO INDIVIDUALS, I WOULD BRING IN REALLY GOOD PLENARY SPEAKERS AND EXEMPLARY PEOPLE THEY CAN LOOK UP TO. FINALLY AS I SAID P30 AS A NAME DOES NOT INSPIRE. BEN BERRES THIS WAS CENTRAL TO HIS MISSION. WHY NOT CALL THIS THE BERRES PROFESSORSHIPS? >> THEY ARE GOING TO THINK I PAID YOU TO SAY THIS BECAUSE THAT'S EXACTLY WHAT I SAID. AND SO WE HAD THOUGHT ABOUT THAT. THAT WAS ON THE TABLE. YOU'LL NOTICE I SNUCK IN AN ACRONYM. THE ACTUAL NAME OF THE PROGRAM IS POWER, BUT SOME INDIVIDUALS THOUGHT MAYBE THAT WAS TOO CHEESY BUT THANK YOU FOR VALIDATING ME. >> BY THE WAY, IT IS KIND OF INCREDIBLE THAT WE HAVE TALKED. MICHELLE BROUGHT THIS UP AND WE'VE TALKED ABOUT THAT. I ACTUALLY DON'T KNOW WHETHER WE WOULD BE ALLOWED TO DO THAT. >> WHAT WOULD POSSIBLY KEEP YOU FROM DOING THAT? >> LET'S DISCUSS IT LATER, IT'S NOT THE ONLY PROGRAM PROPOSED TO BE NAMED AFTER BEN. >> I DON'T THINK BEN WOULD MIND TO SHARE HIS NAME WITH A FEW. >> I'M SURE BEN WOULDN'T MIND. IT'S A GREAT IDEA. >> SO THIS SOUNDS TERRIFIC. I HAD A ENOUGH OF QUESTIONS, ONE TECHNICAL. WHAT IS AN ORGANIZATIONAL UNIT IN THE SENSE OF THIS BECAUSE -- WELL, I'LL LEAVE IT AT THAT, WHAT IS AN ORGANIZATIONAL UNIT? >> THAT IS OUR WAY, SO WHEN WE SPOKE ABOUT THIS, WE WENT BACK AND FORTH IN TERMS OF HOW YOU CREATE A COHORT IF PEOPLE ARE SPREAD ALL AROUND, AND WE TALKED ABOUT OR WE SPOKE ABOUT DEPARTMENTS, BUT WE SAID GIVEN THE NATURE OF NEUROSCIENCE AND INTERDISCIPLINARY NATURE OF IT, DEPARTMENT DOESN'T FIT. WHEN I WAS AT PENN, LIKE A DEPARTMENT DOESN' REALLY MEAN ANYTHING IN TERMS OF HOW IT COULD BE STRUCTURED IN THE INTERACTION AND ENVIRONMENT. AND SO THAT'S OUR REALLY POOR WORD CHOICE FOR TRYING TO DESCRIBE THAT. >> I GUESS THE REASON I'M ASKING IS THAT YOU CAN EASILY IMAGINE A PLACE THAT HAS A LOT OF INTERACTION AMONG THE NEUROSCIENTISTS IN A FACULTY OF ARTS AND SCIENCES THAT PEOPLE IN A NEUROSCIENCE DEPARTMENT AT A MEDICAL SCHOOL AND PEOPLE IN A NEUROLOGY DEPARTMENT, AND ARE THEY IN AN ORGANIZATIONAL UNIT BECAUSE THEY HAVE ALL GOTTEN APPOINTMENTS AT THE SAME UNIVERSITY OR ARE THEY THREE DIFFERENT PLACES AND YOU PROBABLY WANT OR MAYBE YOU WANT TO ENCOURAGE THAT SORT OF INTERACTION BUT IN COORDINATED RECRUITING. >> WITHIN THE FOA WE'LL HAVE TO ARTICULATE JUST THAT, WHAT WE'RE DESCRIBING, WITH THE THOUGHT THAT WE REALLY DO WANT THE POSSIBILITY OF THEM COMING TOGETHER AND HAVING THE INTERACTION TO BE REAL AND NOT DESPERATE PEOPLE FLUNG ACROSS A UNIVERSITY SYSTEM. >> GOT IT. THE OTHER ONE, I DON'T WANT TO TAKE TOO MUCH TIME, I ASSUME THAT THE SYSTEM MUST BE THAT THEY APPLY, INDICATE THE POOLS OF PEOPLE WHO HAVE APPLIED FOR FACULTY JOBS BUT CAN'T IDENTIFY THE SPECIFIC INDIVIDUALS PROPOSING TO HIRE BECAUSE OF TIMING FROM FILING THIS APPLICATION TILL IT'S FUNDED VERSUS TIMING OF MAKING OFFERS TO INDIVIDUALS WHO ARE ACTUALLY IN THE MARKET. >> YEAH, JUST LIKE ARA, TO BE NAMED. YOU DON'T HAVE TO HAVE SOMEONE SITTING THERE SHOVEL READY TO HIRE. >> SO IT'S GOING -- SOUNDS LIKE IT'S PROBABLY GOING TO BE A RICH GETTING RICHER SITUATION BECAUSE THE KINDS OF ORGANIZATIONAL UNITS THAT WE'LL BE ABLE -- WILL BE ABLE TO SUPPORT THREE PEOPLE WILL BE LARGE TO SAY WE HAVE THE ROOM, THE SPACE, THE LAB SPACE, THE START-UP FUNDS. >> DO YOU WANT TO TALK ABOUT THE TRANSITIONAL NATURE OF THE HIRES? >> YEAH. YOU KNOW, EVERYBODY -- WE HEAR THAT A LOT. IT'S A REASONABLE WORRY ABOUT THE RICH GETTING RICHER. WHEN YOU START LOOKING AMOUNT WHO IS THE RICH, THERE'S A LOT OF RICH OUT THERE. THIS IS PROBABLY NOT FOR THE POOR. BUT THERE'S NOT A LOT OF POOR OUT THERE. YOU KNOW, THE OTHER PART OF THAT IS WE IN FACT ARE NOT EXPECTING ALL THE HIRES TO OCCUR AT ONCE. IT'S A FIVE-YEAR AWARD. AND WE WOULD ANTICIPATE IT WILL BE STAGGERED AND IT'S NOT -- ALTHOUGH YOU COULD HAVE IDENTIFIED SOMEBODY, IT'S NOT THAT YOU SHOULD HAVE IDENTIFIED SOMEBODY. OUR ASSUMPTION, THERE ARE WOMEN AND MEMBERS OF VARIOUS GROUPS JUST DISABLED PEOPLE AND MINORITIES THAT THEY ARE OUT THERE, THERE ARE POSTDOCS, AND THIS IS AN INSTITUTION COMING WITH A PLAN OVER A PERIOD OF YEARS TO HIRE PEOPLE AND IF IT'S A GOOD PLAN WE ASSUME THE PEOPLE ARE OUT THERE. >> AND IF THE UNIT DOES A GREAT JOB, BRINGS IN PEOPLE, THEY ARE STAYING, THEY ARE GETTING PROMOTED, WHAT MAY BE QUICK AT FIVE YEARS TO GET PROMOTED, CAN THEY RENEW THEIR P30 AND KEEP GOING? >> GOOD QUESTION. >> THAT'S A GREAT QUESTION. >> WE'RE TRYING TO GET MONEY FOR THIS FIRST ISSUE. [LAUGHTER] I'LL SAY I HOPE SO. >> YOU KNOW, I THINK LIKE ANYTHING, IF IT WORKS AND IT'S INCREDIBLY SUCCESSFUL, PEOPLE WILL LOOK FAVORABLY AT IT. IF IT DOESN'T WORK, NOBODY'S GOING DO WANT TO RENEW IT. >> WE'LL HAVE TO FIGURE OUT IN THE FUTURE. AMY, BEV AND DEARA. WE'RE TIGHT FOR TIME BECAUSE FRANCIS COLLINS IS COMING AT A CHOREOGRAPHED TIME. >> I'LL ASK MY QUESTION QUICKLY. ASSUMING HIRES ARE NOT IDENTIFIED AT THE TIME OF APPLICATION I WORRY A LITTLE BIT ABOUT HOW YOU COULD ADVERTISE THOSE POSITIONS BECAUSE I THINK MOST INSTITUTIONS MAY HAVE PROBLEMS WITH SAYING THESE FACULTY POSITIONS ARE OPEN ONLY TO WOMEN AND UNDERREPRESENTED MINORITIES. THEY ARE ALWAYS ENCOURAGED TO APPLY BUT I DON'T KNOW MANY INSTITUTES WILL FEEL COMFORTABLE DOING THAT AND IF THEY DIDN'T HAVE THE FUNDS TO HIRE SOMEONE WHO IS A HIGHLY QUALIFIED CANDIDATE WHO WASN'T IN ONE OF THOSE GROUPS THAT MIGHT MAKE THEM OPEN A LITTLE BIT TO CHARGES OF, YOU KNOW, SOME KIND OF REVERSE DISCRIMINATION. SO THAT'S THE ONLY THING I THINK WE'LL HAVE TO THINK THROUGH HOW THAT COULD BE DEALT WITH. I THINK THIS IS A FABULOUS PROGRAM. 100% SUPPORTIVE. BUT THAT'S -- I CAN SEE THAT AS BEING A POTENTIAL CHALLENGE OF THIS PROGRAM. AND THEN I WAS WONDERING JUST A QUICK -- IS IT GOING TO BE OPEN TO PhDs AND MD/PHDs? THAT WOULD CHANGE THE DYNAMICS IF IT WAS MD/PHDs, VIABLE -- VALUABLE TO THEM. IS THERE A WAY TO EXTEND BEYOND FIVE YEARS AS LESS THAN FULL TIME? WE ALL KNOW THE TIME OF THE FIRST FACULTY POSITION IS A VERY COMMON TIME, PARTICULARLY FOR WOMEN TO START FAMILIES. AND IT CAN BE HIGHLY CHALLENGING TO BE STARTING A RESEARCH PROGRAM AND STARTING A FAMILY SIMULTANEOUSLY AND MANY WOMEN WOULD LIKE THE OPPORTUNITY I THINK, AND MEN ALSO POSSIBLY, TO MAYBE NOT HAVE IT BE 100% FOR FIVE YEARS OR MAYBE 80% FOR SIX YEARS OR SOMETHING LIKE THAT. AND WILL WE HAVE THAT KIND OF FLEXIBILITY? THAT IS STILL A PLACE WE LOSE A LOT OF EARLY CAREER WOMEN BECAUSE THAT IS A VERY HARD BALANCE TO STRIKE. >> WHY DON'T WE COLLECT THE QUESTIONS AND THINK ABOUT IT. I DON'T THINK YOU'LL HAVE EASY ANSWERS. THESE ARE IMPORTANT POINTS. QUICKLY BEV AND DEERA. >> I'M 100% SUPPORTIVE, MY QUESTION IS SIMPLE. HOW DO YOU SHOW SUCCESS IN FIVE YEARS WITH THREE? IT'S JUST DIFFICULT TO MAKE THE MATH WORK, IN MY MIND. SO, YOU KNOW, LIKE YOU SAID, YOU SORT OF LIFT ALL BOATS. IS THERE EVIDENCE THAT THIS PROGRAM IS -- THE INTENTION IS THREE BUT ENDS UP BEING 13, HOW YOU CAN SHOW SUCCESS IN FIVE YEARS. >> SHORT TERM, LONG TERM. >> I CAN DEFER MY QUESTION ALONG THE LINES OF AMY'S FIRST QUESTION. I'M INTERESTED IN KNOWING ABOUT ALL THE DIFFERENT DIVERSITY THAT WILL COUNT AND INTERACT BUT IT'S NOT URGENT. >> IF YOU'RE NOT USING THE MIC TURN IT OFF. AFTER FRANCIS SPEAKS WE MIGHT WANT TO FINISH THIS DISCUSSION. I DON'T WANT TO CUT IT SHORT. LARRY? >> I'LL MAKE A QUICK COMMENT AND PERHAPS WE CAN PICK UP ON IT AFTERWARDS. IN SOME WAYS THIS IS AT LEAST THE INTENT SIMILAR TO THE HANNAH GRAY PROGRAM HHI INITIATED A YEAR AGO. SO THE EMPHASIS THERE IS ACTUALLY ON APPLICANTS, IT'S AN OPEN POOL FOR APPLICATIONS, IT FUNDS FOUR YEARS OF POSTDOC FOLLOWED BY FOUR YEARS OF ONE'S ASSISTANT PROFESSORSHIP FOR WOMEN AND MINORITIES. IT MIGHT BE INTERESTING TO DISCUSS THE DIFFERENCE BETWEEN THIS PROGRAM AND THE ONE YOU'RE PROPOSING. >> OKAY. WE SHOULD PICK THIS UP AGAIN AFTER FRANCIS TALKS BECAUSE THESE ARE IMPORTANT ISSUES. I DON'T WANT TO TRUNCATE THEM. WHY DON'T WE TAKE A 10-MINUTE BREAK. HE'S SPEAKING AT 10:30. TRY TO BE BACK IN YOUR SEATS IT'S A PLEASURE TO INTRODUCE DR. FRANCIS COLLINS, 16TH DIRECTOR OF THE NIH. WELL KNOWN PROBABLY TO EVERYBODY HERE IN THE ROOM. PREVIOUS DIRECTOR OF THE NATIONAL GENOME RESEARCH INSTITUTE AND PIONEER IN GENETIC RESEARCH, MANY CONDITIONS ARE NEUROLOGICAL HE WORKED WITH, HUNTINGTON'S, AND NEUROENDOCRINE TUMORS, HE'S AN HONORARY& NEUROSCIENTIST, AND ALSO BEEN A TREMENDOUS LEADER HERE AT NIH AND WE'VE BEEN MEETING WITH HIM. HE WILL TELL YOU ABOUT SOME MEETINGS. ALL I'D SAY IS THAT WE ARE SO GRATEFUL TO HAVE DR. COLLINS STICK WITH NIH OVER THIS TRANSITION PERIOD, IT'S JUST BEEN FANTASTIC. I DON'T KNOW WHAT WOULD HAPPEN WITHOUT YOU AT THIS POINT. [APPLAUSE] ABSOLUTELY. HE'S ALSO A WONDERFUL GUITAR PLAYER AND GAVE ME A GUITAR PICK, BUT I DON'T PLAY THE GUIDING GUITAR. FRANCIS, THANK YOU VERY MUCH. >> THANKS, WALTER. THANKS FOR THE OPPORTUNITY TO COME AND ADDRESS THIS ADVISORY COUNCIL COMPOSED OF SUCH DISTINGUISHED INDIVIDUALS WHO ARE VISIONARIES ABOUT WHERE WE NEED TO GO AT A VERY EXCITING TIME SCIENTIFICALLY IN NEUROSCIENCE. AND IT IS WONDERFUL HAVING WALTER AS A COLLEAGUE IN MANY AREAS I'M GOING TO TOUCH ABOUT. WE'RE SEEING A LOT OF EACH OTHER LATELY BECAUSE OF THE MANY THINGS WE'VE SHARED VISIONS AND HOPES ABOUT INCLUDING THE BRAIN INITIATIVE AND CERTAINLY AT THIS POINT A VERY HEAVY FOCUS ON PAIN AND WHAT WE MIGHT BE ABLE TO DO ABOUT THE OPIOIDS PUBLIC HEALTH CRISIS WHICH I'M ALSO GOING TO SAY SOMETHING ABOUT AND WHICH YOU ARE GOING TO BE ASKED TO LOOK AT IN TERMS OF CONCEPT CLEARANCES LATER ON TODAY.& SO ALWAYS A GREAT CHANCE TO HAVE FOR ME TO BE ABLE TO COME AND MEET WITH COUNCILS AND HEAR WHAT'S ON YOUR MIND. I'M GOING TO SPEAK FOR 20 MINUTES AND HAVE A CHANCE TO HEAR YOUR COMMENTS. I'M GOING TO HAVE TO DASH OUT AT 11:00 OR SHORTLY THERAFTER BECAUSE OF A MEETING WITH THE FDA COMMISSIONER. THERE'S A LOT GOING ON RIGHT NOW. SO WITHOUT FURTHER ADO, I'M GOING TO HIT A FEW HIGHLIGHTS, THINGS THAT I SUSPECT YOU'VE ALREADY BEEN TALKING ABOUT BUT JUST A QUICK PERSPECTIVE FROM ME. THE NEWEST KID ON THE BLOCK IN TERMS OF EVENTS IN JUST THE LAST COUPLE WEEKS BECAUSE THIS JUST GOT ANNOUNCED A FEW DAYS AGO IS THIS FOURTH PROGRAM IN THE ACCELERATING MEDICINES PARTNERSHIP PREVIOUSLY STUDDING TYPE 2 DIABETES, ALZHEIMER'S DISEASE AND RHEUMATOID ARTHRITIS AND LUPUS AND NOW ADDED A FOURTH PROGRAM ON PARKINSON'S DISEASE, AND MUCH CREDIT TO WALTER WHO HAS HELPED A LOT BUILD THE MOMENTUM BEHIND THIS EFFORT WHICH NOW INCLUDES PARTNERS YOU SEE THERE, AND THE GOALS WHICH INCLUDE PARTICULARLY A FOCUS ON BIOMARKERS, STANDARDIZED ASSAYS, TRYING TO FIGURE OUT HOW WE CAN UNDERSTAND SUBSETS OF PARKINSON'S DISEASE, AND THEREFORE ALSO IDENTIFY BIOMARKERS THAT ARE CORRELATING WITH RESPONSE, ALL OF THE PARTNERS THAT YOU SEE HERE PUTTING REAL MONEY ON THE TABLE AS WELL AS WILLINGNESS TO TAKE PART IN AN INTENSELY COLLABORATIVE EFFORT WHERE ALL THE DATA WILL BE MADE ACCESSIBLE TO ANYBODY WHO IS INTERESTED IN IT. INTERESTING IN THIS CASE, IN ADDITION TO COMPANIES, WE HAVE VERILY AS A PARTNER, WE HAVE MICHAEL J. FOX FOUNDATION, FDA VERY MUCH INVOLVED AS WELL, AND WITH NINDS AS THE LEAD AT NIH. SO WATCH THIS SPACE. I THINK SOME VERY INTERESTING SCIENCE IS GOING TO HAPPEN HERE BY BRINGING TOGETHER A REALLY CAPABLE SCIENTIFIC LEADERS FROM BOTH THE PUBLIC AND PRIVATE SECTORS IN AN OPEN ACCESS FORMAT AND FIGURING OUT HOW WE CAN TOGETHER DO THINGS WE COULD NOT HAVE DONE SEPARATLY. OF COURSE, THE BRAIN INITIATIVE HAS BEEN AN INCREDIBLY INTENSE FOCUS FOR ALL OF US AT NIH SINCE IT WAS INITIATED AND ANNOUNCED BY PRESIDENT OBAMA BACK NOW THREE YEARS AGO. THE WAY THIS PROJECT IS GOING FORWARD IS EXHILARATING TO OBSERVE. WE HAVE OF COURSE A BLUEPRINT FOR WHAT THE OVERALL BRAIN INITIATIVE SHOULD LOOK LIKE, SOMETHING THAT WAS PUT TOGETHER BY THAT REMARKABLE PANEL THAT CORI BARGMANN AND BILL NEWSOME LED, THAT'S BEEN VERY VALUABLE IN TERMS OF PROVIDING US WITH A PATH FORWARD OF HOW THIS PROJECT OUGHT TO BE MANAGED AND WHAT SCIENCE WE OUGHT TO BE PARTICULARLY ENCOURAGING AND AS YOU KNOW THE EARLY STAGES OF THIS FOCUSED PARTICULARLY ON TECHNOLOGY DEVELOPMENT, GRATIFYING TO SEE GRANTEES HAVE BEEN ENGINEERS AND WE'RE BRINGING THEM INTO THE FOLD AT SCIENTISTS. THE 21ST CENTURY CURES ACT PASSED BY BOTH HOUSES SAW FIT TO ENDORSE THE BRAIN INITIATIVE AS A HIGH PRIORITY FOR AMERICAN SCIENCE, AND THERE ARE PUT IN PLACE A TRAJECTORY FOR SUPPORTING IT UNTIL 2025, OUTSIDE OF THE REGULAR YEARLY APPROPRIATIONS PROCESS, GIVING US THE CONFIDENCE THAT THIS IS A PROJECT THAT WE CAN REALLY INVEST IN AND NOT WORRY ABOUT IDEAS OF DIMINISHED ENTHUSIASM. IT'S BEEN VERY STRONGLY ENDORSED BY THE CONGRESS. THE BRAIN AWARDS, AS YOU NO DOUBT HAVE BEEN HEARING ABOUT, ARE ALL OVER THE COUNTRY. JUST IN THIS CURRENT YEAR 110 NEW AWARDS ADDING UP TO 17 $170 MILLION, $543 MILLION SINCE IT BEGAN. WALTER AND I HAVE TALKED ABOUT THIS WITH JOSH GORDON WHO CO-LEADS WITH WALTER THE OVERALL MANAGEMENT OF THE BRAIN INITIATIVE TO THINK ABOUT WHETHER WE SHOULD HAVE A RELOOK AT THE 10-YEAR PLAN WITH A FIELD& MOVING AS QUICKLY AS NEUROSCIENCE, THE IDEA YOU HAVE A 10-YEAR PLAN THAT STAYED EXACTLY THE SAME FOR A DECADE DOESN'T SEEM TOO LIKELY TO BE THE RIGHT ANSWER. SO THERE IS AS YOU CAN SEE FROM THIS TIME LINE A SERIES OF STEPS NOW GETTING UNDERWAY AND WILL LEAD TO BY THE SUMMER OF 2019, WHICH IS NOT THAT FAR OFF, A NEW BRAIN STRATEGIC PLAN FOR THE SECOND HALF OF THIS DECADE OF EFFORT AND WILL LEAD THEREFORE TO FOAs BY WINTER OF 2020. AND THE CHARGE TO THE NEW WORKING GROUP IS TO UPDATE THE SCIENTIFIC VISION THAT'S LAID OUT TO GUIDE THIS SECOND HALF, IDENTIFY VALUABLE AREAS OF NEW AND CONTINUED TECHNOLOGY DEVELOPMENT AND CONSIDER THE UNIQUE CONTRIBUTIONS THAT CAN BE MADE THAT WOULDN'T OTHERWISE HAPPEN. SO LOOKING FORWARD TO A VERY INTENSE TIME AS THIS WORKING GROUP GOES THROUGH THAT PROCESS, AND NO DOUBT WILL BE COLLECTING LOTS OF IDEAS FROM LOTS OF PEOPLE BEGINNING WITHIN MARCH 2018 AN RFI ON BRAIN 2025, SO WE WANT TO HEAR FROM YOU. ALSO WE ARE CONCERNED GIVEN EMPHASIS ON NEEDS FOR PAIN THAT WE TAKE FULL ADVANTAGE OF WAYS IN WHICH THE BRAIN INITIATIVE CAN HELP WITH FURTHERING THE UNDERSTANDING OF THE BASIC SCIENCE OF PAIN, THERE IS A CONNECTION HERE JUST ANNOUNCED IN THIS NEW FOR FY 2018 NOTICE OF SUPPORT FOR RESEARCH ON THE FUNDAMENTAL NEURO BIOLOGY OF PAIN PROCESSING, AND OF COURSE WHEN WE SAY BRAIN WE'RE ALSO THINKING ABOUT SPINAL CORD AS A PLACE WHERE A LOT OF SCIENCE NEEDS TO HAPPEN TO FULLY UNDERSTAND THE NATURE OF PAIN AND MANY OTHER FUNCTIONS. BUT NOW LET ME SWITCH TO THE OPIOID CRISIS, WHERE I'M GOING TO SPEND MOST OF THE REST OF THE TIME BECAUSE THIS IS SUCH AN AREA OF INCREDIBLY HIGH IMPORTANCE. I DON'T THINK 20 YEARS AGO IT COULD HAVE BEEN IMAGINED THAT WE WOULD BE WHERE WE ARE. THAT WAS THE POINT AT WHICH THERE WAS A GENERAL SENSE THAT PAIN WAS THE FIFTH VITAL SIGN, THAT PAIN OUGHT TO BE TREATED, THAT EVERY PATIENT SHOULD BE ASKED IF THEY ARE HAVING PAIN AND IF SO SOME INTERVENTION SHOULD BE DONE, THE INTERVENTION OFTEN WAS A PRESCRIPTION. THERE WAS A SENSE SOMEHOW LONG-ACTING OPIOIDS WOULD NOT END UP BEING ADDICTIVE, IF THAT INDIVIDUAL WAS SUFFERING CHRONIC PAIN, SOMETHING WE NOW KNOW IS ABSOLUTELY WRONG. OVER THE COURSE OF TIME BEGINNING IN THE MID-1990s GOING FORWARDS THE NUMBER OF OPIOID PRESCRIPTIONS BEGAN TO RISE DRAMATICALLY AND WE SEE OURSELVES IN A CIRCUMSTANCE LOOKING AT THE MAP OF THE UNITED STATES WHERE IN THE SPACE OF THE LAST 17 YEARS THERE HAS BEEN A TRULY FRIGHTENING INCREASE IN OPIOID ADDICTION AND MOST FRIGHTENING OF ALL DEATH RATES FROM OVERDOSES. YOU CAN SEE IN 1999 OTHER THAN A LITTLE BIT OF ACTIVITY PERHAPS IN THE APPALACHIANS AND SOUTHWEST, OVERDOSE DEATH RATES WERE QUITE MODEST, BY 2016 THE WHOLE COUNTRY HAS CHANGED, AND YOU CAN SEE DRAMATICALLY WHAT'S HAPPENED IN PLACES LIKE WEST VIRGINIA AND OHIO AND IN THE SOUTHWEST. BUT VIRTUALLY NO STATE, NO COUNTY, HAS BEEN FREE OF SOME IMPACT HERE IN TERMS OF WHAT HAS HAPPENED. UNTIL RECENTLY, 80% OF THOSE WHO WERE ADDICTED TO OPIOIDS STARTED OUT ON PRESCRIPTIONS. SO WE HAVE TO TAKE SOME RESPONSIBILITY FOR THE WAY IN WHICH OUR MEDICAL CARE SYSTEM CONTRIBUTED TO THIS DREADFUL CIRCUMSTANCE, MORE RECENTLY THOSE WHO WERE ADDICTED TO OPIOIDS ARE MORE LIKELY TO HAVE STARTED WITH INJECTABLE HEROIN BECAUSE WE MADE IT MORE DIFFICULT FOR PRESCRIPTIONS TO BE AVAILABLE. THE NUMBER OF ADDICTS OVER 2 MILLION IN THE UNITED STATES FACING ALL OF THEM SIGNIFICANT RISKS, ESPECIALLY NOW AS THE HEROIN SUPPLY IS LACED WITH FENTANYL AND CARFENTANIL, POTENT AND DANGEROUS. YOU CAN SEE WHAT'S HAPPENED IN ITEMS OF OPIOID OVERDOSE DEATHS, 42,000 OF THEM IN 2016, THE LAST YEAR OF FULL DATA. THE RED LINE SYNTHETIC INCLUDING OPIOIDS GOING UP STRONGLY. YOU CAN SEE THE RELATIONSHIP IN TERMS OF POTENCY EXPLAINS WHY EVEN A LITTLE BIT OF FENTANYL OR WORSE YET CARFENTANIL CAN RESULT IN DEATH, IT TURNS OUT TO BE LETHAL. FIRST RESPONDERS MUST BE PREPARED TO TREAT PEOPLE USING NALOXONE IF PRESENT IN SUFFICIENT DAYSES, WE AT NIH HAD HAVE A LOT TO DO WITH TRYING TO ADDRESS THIS SITUATION IN TERMS OF TREATMENT OF OVERDOSES, IN TERMS OF TREATMENT OF ADDICTION, AND I WANT TO TELL YOU EVEN MORE ABOUT THAT BUT, AGAIN, I THINK IT'S TIME FOR ALL HANDS ON DECK. WE AT NIH HAVE BEEN ORGANIZING A NUMBER OF MEETINGS WERE INDUSTRY, ADVOCATES, TO SEE THE WAY THE BEST SCIENCE CAN BE BROUGHT TO BEAR ON THIS PUBLIC HEALTH CRISIS, JESSICA NICKEL QUOTED HERE HAS BEEN A VERY ARTICULATE VOICE FOR THOSE WHOSE FAMILIES, WHO HAVE INDIVIDUALLY BEEN AFFECTED BUT, AGAIN, CALLING US TO ACTION, LOSING A GENERATION OF AMERICANS TO AN ILLNESS WE KNOW HOW TO TREAT IF WE HARNESS THE WILL, THE GOAL HAS TO BE TO DO THAT KIND OF HARNESSING. THE NUMBERS ARE TROUBLING. WE MUST REMEMBER HOWEVER IN OUR EFFORTS TO DEAL WITH THE OPIOID CRISIS THAT THERE ARE 25 MILLION ADULTS WHO HAVE PAIN EVERY DAY, AND WE DON'T HAVE NECESSARILY GOOD ANSWERS FOR THEM. IN FACT FOR MOST INSTANCES WE DO NOT. WE KNOW OPIOIDS ARE OFTEN THE OPPORTUNITY THAT'S PUT FORWARD BUT ARE NOT PARTICULARLY APPROPRIATE OR EFFECTIVE IN MANY INSTANCES OF CHRONIC PAIN. I'VE MENTIONED ALREADY THE NUMBER OF INDIVIDUALS WHO ARE ALREADY ADDICTED. WE KNOW THE TREATMENT IS AVAILABLE FOR ADDICTION, USING MEDICATION, WE ALSO KNOW TREATMENT PROGRAMS THAT DO NOT USE MEDICATION HAVE EXTREMELY HIGH RELAPSE RATES. AND THE IDEA THAT A 28-DAY DETOXIFICATION PROGRAM WHICH DOES NOT INVOLVE MEDICATION IS GOING TO HELP PEOPLE WHO ARE OPIOID ADDICTED IS SIMPLY NOT THE CASE YET THERE ARE MANY PROGRAMS ADVERTISING THEMSELVES TO PEOPLE DESPERATE FOR HELP. WE HAVE A HUGE PUBLIC EDUCATION ISSUE AS WELL AS NEED TO MAKE MAT AVAILABLE TO THOSE LOOKING FOR IT, CURRENTLY DRASTICALLY UNDERUTILIZED, ONLY A TINY PERCENTAGE OF PEOPLE ADDICTED TO OPIOIDS AND SEEKING TREATMENT ULTIMATELY END UP GETTING SUCCESSFUL TREATMENT THROUGH SUCH PROGRAMS. AND PART OF THE PROGRAM, WE DON'T KNOW HOW LONG PEOPLE NEED TO BE TREATED. THIS IS NOT THE CIRCUMSTANCES WHERE 28 DAYS AND YOU'RE DONE. MAYBE SIX MONTHS, MAYBE A YEAR, MAYBE LONGER, MAYBE THIS IS A DISEASE LIKE DIABETES WHERE YOU DON'T SAY I'M JUST GOING TO GET THROUGH MY TREATMENT AND STOP. MAYBE THIS IS SOMETHING THAT ONCE YOU HAVE REWIRED YOUR BRAIN BY OPIOIDS, YOU MAY NEED THAT KIND OF LIFELONG INTERVENTION. WE DON'T HAVE ENOUGH DATA TO KNOW ABOUT THAT. CERTAINLY WE COULD COME UP WITH OTHER STRATEGIES GOING DOWNSTREAM ABOUT HOW TO PREVENT THIS, BUT WE NEED TO BE SURE THAT WE'RE NOT ABANDONING THOSE INDIVIDUALS WITH SERIOUS PAIN, SO OTHER ALTERNATIVES, NOT ADDICTIVE BUT POTENT MEDICINES ARE VERY MUCH NEEDED. HOW DO WE DO THIS? WE NEED IN THREE DIFFERENT AREAS RESEARCH TO MOVE FORWARD, THE THREE AREAS IN THIS TRIANGLE THAT YOU SEE. WE DO NEED TO FIND NO AND BETTER AND INNOVATIVE AND PATIENT-FRIENDLY APPROACHES TO OPIOID ADDICTION TREATMENT. RIGHT NOW WE HAVE METHADONE, BUPRENORPHINE, METH TREKS OWN. NALOXONE WORKS IF YOU GIVE AT THE RIGHT MOMENT BUT WITH THE STRONGER FORMS OF SYNTHETIC OPIOIDS, IT MAY TAKE MORE THAN ONE DOSE BECAUSE BECAUSE APPROACHES LIKE TMS THAT NEED FURTHER EXPLORATION. WE HAVE A ROLE TO PLAY, THAT INCLUDES NINDS, NIDA, THE NATIONAL INSTITUTE OF DRUG ABUSE IS IN THE SPACE OF ADDICTION AND TREATMENT BUT WHEN IT COMES TO PAIN MANAGEMENT THE PAIN CONSORTIUM AT NIH AND WALTER'S ROLE IN LEADING THAT MEAN THAT THIS INSTITUTE NEEDS TO BE IN THE MIDDLE OF TRYING TO FIND THOSE SOLUTIONS. WE'VE DONE A LOT AT NIH IN THIS SPACE, JUST PICKED A FEW EXAMPLES HERE, THE BASIC SCIENCE ARENA DISCOVERING MUTATIONS, RECESSIVE MUTATIONS IN SCN9A WHICH CONES FOR NAV 1.7, SENSITIVITY TO PAIN, TRYING TO FIND OUT A WAY TO COME UP WITH AGONIST OR ANTAGONIST TO THIS SODIUM CHANNEL, I MEANT TO AANTAGONIST. IF WE COULD GIVE PEOPLE TEMPORARY INSENSITIVITY, THAT WOULD BE A WAY. WORKING TO UNDERSTAND THE MU OPIOID RECEPTOR WITH TWO PATHWAYS, THAT MIGHT BE POSSIBLE, THIS IS NOW STARTING TO BE TESTED IN REALITY TO VALUE BIASED AGONISTS BINDING TO THE RECEPTOR AND LEAD TO ANNUAL ANALGESIA BUT NOT THE BETA ARRESTOR PATHWAY, IT'S A PROMISING PATHWAY TO TAKE ADVANTAGE OF A RECEPTOR WE KNOW IS THE MAJOR PLAYER HERE. AND TURN IT INTO SOMETHING SAFER. IN TERMS OF DEVELOPMENT OF THERAPEUTICS, IT IS AN EFFORT BETWEEN NIDA AND A SMALL COMPANY THAT HAS LED TO MOST COMMONLY USED OVERDOSE REVERSAL, NALOXONE, WHAT MOST FIRST RESPONDERS CARRY AROUND WITH THEM NOW. MUCH EASIER TO ADMINISTER AND EASIER TO ADMINISTER BY LAYPEOPLE THAN PREVIOUS INJECTABLE FORM. IN TERMS OF PREMIUM OF ADDICTION, THIS IS AN IMPLANT VERSION OF BUPRENORPHINE WHICH HAS A SIX-MONTH DURATION, VERY VALUABLE IN HELPING INDIVIDUALS TRYING TO GET FREE OF ADDICTION AND DON'T WANT TO TAKE A DAILY PILL, ONCE YOU HAVE THESE IMPLANTED YOU HAVE SIX MONTHS OF TREATMENT. AND VIVITROL, AN INJECTABLE FORM, AN ANTAGONIST WILL MAKE IT THE CASE THAT SOMEBODY WHO IS TRYING TO STAY FREE OF OPIOIDS IS PRETTY MOTIVATED TO DO SO BECAUSE IF THEY DO SEEK OUT AN OPIOID IT'S NOT GOING TO HAVE ANY EFFECT BECAUSE THE RECEPTOR IS BLOCKED. WE WOULD LOVE TO HAVE A VERSION OF THIS THAT LASTS SIX MONTHS INSTEAD OF ONE MONTH BUT THIS IS STILL A BIG DEVELOPMENT. ALL OF THESE ARE THINGS THAT NIH HAS PLAYED A SIGNIFICANT ROLE IN MAKING POSSIBLE. THERE'S MORE WE NEED TO DO IF THERE WAS A CASE FOR ALL HANDS ON DECK, SOME IN THE PRIVATE SECTOR, THIS IS A CASE WE OUGHT TO DEVELOP A PUBLIC/PRIVATE PARTNERSHIP. BUILDING UPON THE POSITIVE EXPERIENCE WITH AMP AND OTHER SUCH PARTNERSHIPS, REACHING OUT TO THE COMPANIES WE THOUGHT HAD SOME SKILLS AND EXPERTISE BRINGING THEM TOGETHER, IT'S AN URGENT PUBLIC HEALTH CRISIS, WE NEED BETTER ALTERNATIVES FOR TREATMENT, OVERDOSE AND PAIN. THERE'S EMERGENCE OF NUMEROUS DRUG TARGETS NOT AS VIGOROUSLY PURSUED AS THEY MIGHT BE, POSSIBILITY OF COMING UP WITH BIOMARKERS TO HELP SEGREGATE OUT PATIENT POPULATIONS WITH CHRONIC PAIN THAT MAY HAVE DIFFERENT MECHANISMS AND RESPOND DIFFERENTLY TO INTERVENTION AND STRONG SUPPORT AT THE HIGHEST LEVEL OF U.S. GOVERNMENT INCLUDINGTHE PRESIDENT OF THE UNITED STATES, THE FDA SCOTT GOTTLIEB MOTIVATED AS IS SAMHSA, AS IS CDC, AS IS CMS. IN TERMS OF ADMINISTRATION PRIORITIES YOU MAY KNOW ABOUT THE PRESIDENT'S COMMISSION ON COMBATING DRUG ADDICTION LED BY CHRIS CHRISTIE. WHEN THEY MADE RECOMMENDATIONS AND EMPHASIZED THIS MONTHS LATER THEY SPECIFICALLY INSTRUCTED NIH TO BEGIN WORKING WITH THE PHARMACEUTICAL INDUSTRY IN THESE TWO AREAS, WHAT WE'RE DOING BEFORE JULY 30 IS TO TRY TO FOLLOW UP ON THAT. SO WHAT HAVE WE DONE? BACK IN APRIL, A YEAR AGO, I HAD THE OPPORTUNITY TO MAKE THE CASE TO THE HEADS OF R&D OF PHARMACEUTICAL INDUSTRIES THIS IS PART OF THEIR RESPONSIBILITY AND OPPORTUNITY AS WELL AND THEY EMBRACED THAT CONCEPT. IN JUNE AND JULY WE RAN A SERIES OF THREE VERY INTENSE CUTTING EDGE MEETINGS, FOCUSED ON WHAT THE OPPORTUNITIES WOULD BE HERE, IN THE VARIOUS AREAS, BOTH IN TERMS OF ADDICTION, TREATMENT, OVERDOSE TREATMENT AND DEVELOPMENT OF PAIN MEDICINES. AND THEN IN SEPTEMBER ADDITIONAL MEETINGS WITH REPRESENTATIVES OF LARGE INDUSTRY, PHARMACEUTICAL COMPANIES, ALSO SMALLER COMPANIES THAT HAVE EXPERTISE IN DELIVERY, THE PHARMACEUTICAL MANUFACTURING ASSOCIATION, PHARMA, THE TRADE ORGANIZATION HAS BEEN VERY DEEPLY ENGAGED AS A PARTNER IN THIS, SINCE THE SUMMER. AND FURTHERMORE WE CONTINUE TO INTERACT WITH THE PRESIDENT'S COMMISSION ABOUT THIS PARTNERSHIP. THE INSIGHTS THAT CAME OUT OF ALL OF THOSE MEETINGS WERE THEN USED TO DEVELOP THE DESIGN PHASE OF THIS PUBLIC/PRIVATE PARTNERSHIP, WHICH IS NOW TAKING SHAPE IN A FAIRLY DETAILED WAY. IN NOVEMBER THROUGH JANUARY A SERIES OF MEETINGS INITIATED TO LOOK AT THESE OPPORTUNITIES, I'M SHOWING YOU HERE ON THE SLIDE THE NAMES OF SOME OF THE PEOPLE WHO HAVE BEEN INVOLVED, CERTAINLY YOU'LL RECOGNIZE THE FOLKS FROM NINDS, BUT YOU CAN SEE MANY OTHERS INCLUDING SOME STRONG LEADERS IN RESEARCH FROM THE PRIVATE SECTOR. AND A VERY IMPORTANT TWO-DAY MEETING WITH MORE THAN 90 INDUSTRY STAKEHOLDERS, AND LOTS OF NIH-ERS AND ACADEMIC EXPERTS ABOUT PAIN AND ADDICTION GATHERING TO TRY TO MAP OUT MUCH MORE PRECISELY WHAT WOULD THE PLAN LOOK LIKE, WHAT WOULD MILESTONES BE, THE COST IF WE WERE GOING TO REALLY SERIOUSLY JUMP INTO THIS EFFORT. SO WHERE ARE WE NOW? WE'RE AT THE POINT OF HAVING A PRETTY WELL DEVELOPED RESEARCH PLAN IN THE FORM OF A WHITE PAPER, WHICH MY TEAM AND I WILL BE TALKING ABOUT THIS AFTERNOON WHICH WE HOPE WILL BE READY FOR PUBLIC DISBURSAL IN THE COURSE OF THE NEXT TWO OR THREE WEEKS WITH SEVERAL PARTS TO IT. IT IS AIMING TO TRY TO COVER ALL THREE OF THOSE POINTS OF YELLOW BOXES IN THAT TRIANGLE I SHOWED EARLIER. WE DO NEED NEW FORMULATIONS AND COMBINATIONS OF MEDICATIONS TO TREAT OPIOID USE DISORDER AND PREVENT OVERDOSES. WE NEED THEREFORE POTENT AND LONGER LASTING ANTAGONISTS BECAUSE OF THE NEED TO BE SURE WE'RE SUCCESSFUL IN REVERSING OVERDOSES FROM THE SYNTHETICS LIKE FENTANYL. IN COMING UP WITH STRATEGIES FOR ADDICTION TREATMENT THE FDA MADE IT CLEAR THEY ARE WILLING TO CONSIDER STRATEGIES THAT INVOLVE OTHER ENDPOINTS FOR TREATMENT OTHER THAN PROOF OF LONG-TERM ABSTINENCE. THAT'S A VERY DIFFICULT ENDPOINT TO ACHIEVE, CERTAINLY IN THE SHORT TERM, AND WILLINGNESS TO CONSIDER SUCH THINGS AS CRAVING AS AN ENDPOINT THAT MIGHT BE QUITE USEFUL IN TESTING ALTERNATIVE APPROACHES TO MAT. THE PART OF THIS THOUGH THAT MOST DEEPLY INVOLVES NINDS AND WHERE WALTER AND LINDA PORTER HAVE BEEN SIGNIFICANT LEADERS IN OUR DISCUSSIONS AND IN WHAT WE HOPE WE CAN NOW DO IS TO ACCELERATE DEVELOPMENT OF ALTERNATIVES, NON-ADDICTIVE TREATMENTS FOR PAIN. IT'S VERY MUCH THE CASE THAT ADVANCES IN NEUROSCIENCE HAVE POINTED TO TARGETS OUTSIDE OF THE MU OPIOID RECEPTOR THAT ARE POTENTIALLY QUITE INTERESTING AND MIGHT LEAD THEN TO ALTERNATIVES THAT COULD BE QUITE POTENT, BUT I DON'T THINK ANYBODY WOULD SAY THAT HAS BEEN MOVING AT THE SPEED THAT YOU WOULD LIKE. IN PART BECAUSE PAIN RESEARCH HAS NOT GOTTEN THE ATTENTION THAT ONE MIGHT HOPE IN THE PRIVATE SECTOR. INDUSTRY IS UNEASY ABOUT WHETHER FDA WILL SMILE UPON APPROACHES TO TREATING CHRONIC PAIN WHEN PEOPLE MAY BE TAKING A PAIN MEDICINE FOR MANY YEARS, THE TOLERANCE FOR ANY KIND OF SIDE EFFECT IS SEEN TO BE QUITE LIMITED. NOW THAT WE'RE IN THIS CRISIS I THINK FDA AND SCOTT GOTTLIEB'S BEEN QUITE OPEN ARE WILLING TO RETHINK BENEFITS AND RISK IN THIS CIRCUMSTANCE THAT WILL HELP. WE ALSO I THINK NEED TO TAKE ADVANTAGE OF INFORMATION THAT'S ALREADY OUT THERE. AND INDUSTRY IN A RATHER UNPRECEDENTED WAY IS WILLING TO OPEN UP SOME OF THE INFORMATION THEY KNOW ABOUT TO SHARE DATA ABOUT PROJECTS THAT THEY HAVE ALREADY CONDUCTED, ATTEMPTING TO TREAT PAIN THAT HAVE NOT WORKED AND WE CAN FIND OUT WHY AND NOT THEN MAKE THE MISTAKE OF CONTINUING TO DO THE SAME FAILED EFFORTS OVER AND OVER AGAIN. AND THAT AGAIN MUCH CREDIT TO INDUSTRY FOR BEING WILLING TO THINK ABOUT THAT. THAT'S VERY COUNTER TO THE USUAL APPROACH WHERE EVERYTHING STAYS BEHIND THE CURTAIN. AND THEY ARE WILLING TO TAKE ASSETS, THAT WOULD INCLUDE COMPOUNDS THEY HAVE ABANDONED FOR BUSINESS REASONS BUT WHICH SOMEBODY ELSE MIGHT NOW BE INTERESTED IN PICKING UP AND SHARING THAT INFORMATION ACROSS INDUSTRY, NIH ACTING AS A NEUTRAL BROKER BECAUSE THEY NEED THAT KIND OF ASSURANCE THIS IS GOING TO BE DONE IN A FAIR WAY. THEY ARE VERY INTERESTED AS WELL IN DEVELOPING AND VALIDATED BIOMARKERS THAT WOULD DIFFERENTIATE THE MECHANISMS OF PAIN, SO THAT YOU COULD HAVE A BETTER OPPORTUNITY IN A CLINICAL TRIAL TO MATCH THE THERAPEUTICS THAT YOU'RE USING WITH WHAT YOU BELIEVE TO BE THE MECHANISM OF PAIN IN THOSE INDIVIDUALS. AS WELL AS COMING UP WITH BIOMARKERS THAT MIGHT PROVIDE A MORE OBJECTIVE AND DIGITAL MEASURE OF THE LEVEL OF PAIN THAT SOMEONE IS EXPERIENCING SINCE WE KNOW HOW DIFFICULT THIS CAN BE, WITH THE VERY STRONG PLACEBO EFFECT, HAVING ADDITIONAL MEASURES OF PAIN WOULD BE QUITE VALUABLE. BUT THEY ALSO RECOGNIZE THAT IF WE'RE SERIOUS ABOUT PUSHING THIS AGENDA, THAT WOULD BE VERY VALUABLE FROM INDUSTRIES' PERSPECTIVE AND NIH TO HAVE A CLINICAL RESEARCH NETWORK READY TO GO WITH PHASE 2 TRIALS, WOULD INCLUDE BIOMARKER VALIDATION, INCLUDE SUBSETS OF PATIENTS THAT HAVE PARTICULARLY HOMOGENOUS KINDS OF PAIN THAT MIGHT BE MORE READILY ADAPTABLE TO CLINICAL TRIALS. MORE ON THIS FROM LINDA PORTER LATER TODAY BECAUSE YOU'RE GOING TO BE ASKED ABOUT TWO CONCEPT CLEARANCES THAT RELATE TO THE ITEMS YOU SEE THERE IN THE RED BOX, WHICH WE VERY MUCH FEEL NEED TO GO FORWARD AS OUR PART OF THIS PUBLIC/PRIVATE PARTNERSHIP. I WANT TO BE CLEAR THIS IS NOT THE ENTIRE AGENDA FOR DEALING WITH THE OPIOID CRISIS, AND WITH THE NEED TO DEVELOP BETTER ALTERNATIVES FOR PAIN NOT FOLDED INTO THE PUBLIC/PRIVATE PARTNERSHIP ALTHOUGH THAT'S BEEN AN INTENSE FOCUS OVER THE LAST YEAR AND WE HOPE WILL BE SOMETHING THAT CAN AGAIN LAUNCHED IN THE FAIRLY NEAR FUTURE AND BY THE WAY THE EXPECTATION THERE IS THAT THE COSTS FOR THAT PARTNERSHIP WILL BE SHARED BETWEEN NIH AND BETWEEN INDUSTRY WHO WILL CONTRIBUTE NOT JUST EXPERTISE BUT ALSO DOLLARS AND THAT IS SOMETHING BEING WORKED OUT THROUGH PHARMACEUTICAL INDUSTRY, THROUGH THE TRADE ORGANIZATION PHARMA. I CAN'T TELL YOU EXACTLY HOW THAT WILL PLAY, WHAT THE DOLLAR FIGURES WILL BE, WHAT THE TIMING WILL BE, BECAUSE THAT'S IN DISCUSSION IN TERMS OF WHAT THE INDUSTRY CONTRIBUTIONS WOULD BE AND WHAT THE GOVERNMENT MAY BE ABLE TO COME UP WITH AS WELL, AS YOU KNOW. WE DON'T HAVE A BUDGET EVEN THOUGH IT IS NOW FEBRUARY 1, AND OUR FISCAL YEAR BEGAN OCTOBER 1, WE'RE TRYING TO MAKE PLANS OF THIS SORT WITHOUT A GREAT DEAL OF CERTAINTY WHAT'S IN OUR CHECKBOOK AND HOPING THIS TIME CONGRESS WILL GET THROUGH THE PROCESS OF MAKING THOSE DECISIONS AND NOT CONTINUALLY PUTTING OFF BY A SERIES OF CONTINUING RESOLUTIONS THE NEXT ONE OF WHICH OF COURSE IS ONLY A WEEK AWAY, IF WE'RE LUCKY ENOUGH NOT TO HAVE A SHUTDOWN. I'M JUST SAYING, SOMETIMES IT'S A LITTLE CHALLENGING TO RUN AN OPERATION THAT'S TRYING TO BE ON THE LEADING EDGE OF BIOMEDICAL RESEARCH FOR THE WHOLE WORLD WHEN YOU DON'T KNOW HALFWAY THROUGH THE FISCAL YEAR WHAT YOU HAVE TO SPEND. I JUST HAD TO SAY THAT. BUT THERE ARE MANY THINGS NIH IS ENGAGED IN, AGAIN NINDS PLAYS A SIGNIFICANT ROLE. WE WANT TO UNDERSTAND THE TRANSITION FROM ACUTE TO CHRONIC PAIN. WE DON'T KNOW ENOUGH ABOUT WHAT HAPPENS AND HOW TO AVOID THAT. RESEARCH INITIATIVE TO DEFINE THAT IS UNDER INTENSE DISCUSSION. WE ALSO NEED TO COME UP WITH OTHER TECHNOLOGIES THAT WOULD ALLOW US TO DISCOVER NOVEL PAIN TARGETS. I WOULDN'T SAY WE KNOW THE WHOLE UNIVERSE OF TARGETS AT THIS POINT. THERE'S PROBABLY MANY MORE. AND YOU CAN SEE ALSO A RESEARCH INITIATIVE TO LEVERAGE TECHNOLOGIES COMING FROM THE BRAIN INITIATIVE WE WANT TO BE SURE THAT WE'RE TAKING FULL ADVANTAGE OF THOSE. AND AGAIN GOING NEUROTECHNOLOGIES TO BE SURE THAT WE'RE IMPROVING DEVELOPMENT OF THERAPEUTICS. I'LL FINISH BY SAYING IT WAS INTERESTING FOR ME TO READ WHAT WALTER WROTE, THIS JUST GOT POSTED A COUPLE DAYS AGO, ABOUT WHAT'S HAPPENED OVER THE COURSE OF THE LAST YEAR. I SUSPECT HE COVERED SOME OF THIS IN THIS IS DIRECTOR'S REPORT A LITTLE BIT AGO. WE ARE CERTAINLY AT THIS REMARKABLE MOMENT IN TERMS OF SCIENTIFIC OPPORTUNITY. IT'S INTERESTING WE ALSO FEEL PARTICULARLY BECAUSE OF THE OPIOID CRISIS AT A PARTICULAR INTENSE MOMENT OF RESPONSIBILITY, SO WE'VE GOT TO PUT THAT TOGETHER. THE OPPORTUNITY, THE RESPONSIBILITY, IT'S A GREAT TIME TO BE A SCIENTIST, ALSO A MOMENT WE'RE CALLED UPON TO STRETCH OURSELVES IN A SPECIAL WAY TO TRY TO DO SOMETHING TO TURN AROUND WHAT IS AN UNANTICIPATED AND UNPRECEDENTED SITUATION WHERE MORE PEOPLE ARE DYING NOW OF OPIOID OVERDOSES THAN DIED OF HIV/AIDS AT THE PEAK OF THAT EPIDEMIC AND YET I DON'T THINK WE'VE FULLY MARSHALLED THE PUBLIC UNDERSTANDING OF THAT. THAT'S ANOTHER THING WE NEED TO WORK ON TOGETHER. I PROMISE FROM MY PERSPECTIVES THIS IS GOING TO BE AN EXTREMELY HIGH PRIORITY AND WE'LL DO EVERYTHING TO PULL RESOURCES AND CONVINCE OTHERS TO WORK WITH US, SUCCESSFUL ONLY WITH THE FULL SUPPORT WITH THE PEOPLE IN THE INSTITUTE OF NEUROLOGICAL DISEASES AND STROKE TO WHOM I'M GRATEFUL, TO ALL OF YOU FOR THE CHANCE TO SPEAK ABOUT THIS. WITH THAT, I'LL BE GLAD TO TAKE ANY QUESTIONS YOU MIGHT HAVE. THANK YOU. >> BEV. >> THAT WAS REALLY EXCITING AND INFORMATIVE. I WONDER IF YOU CAN COMMENT A LITTLE BIT ON THE CONVERSION ISSUE. FOR EXAMPLE CHILDREN EXPOSED TO ACUTE PAIN, BREAK A LEG, GO TO THE DENTIST OR YOUNG ADULTS, AND WHAT KIND OF RESEARCH IS BEING DONE TO INVESTIGATE HOW MUCH MORE PLIABLE THOSE BRAINS MAY BE TO CONVERT TO A CHRONIC USER FIVE YEARS DOWN THE ROAD, TEN YEARS DOWN THE ROAD? >> TWO THINGS THAT WORK THERE. ONE IS WHAT'S HAPPENING IN TERMS OF THE PHYSIOLOGY OF PAIN ITSELF IN TERMS OF HOW DOES AN ACUTE EPISODE, LET'S SAY BROKEN BONE, RESOLVE ITSELF, SETTING ASIDE WHAT THE THERAPEUTIC INTERVENTION WAS. THAT'S A HUGE BLACK BOX IN TERMS OF WHAT THAT TRANSITION LOOKS LIKE. WE MAYBE HAVE MORE IN THE WAY OF STATISTICS, MICHIGAN DID A RECENT STUDY OF PATIENTS WHO COME IN FOR SURGERY, AND LOOK TO SEE WHAT PROPORTION OF THOSE END UP AFTER KNEE REPLACEMENT, ENDING UP NOT JUST WITH ACUTE EPISODE BUT CHRONIC PAIN. A DISTURBINGLY HIGH NUMBER, IN THE TEENS PERCENTAGE-WISE, YOU WOULD LOVE TO KNOW PREDICTORS, THEY DID PUBLISH SOME OF THOSE. >> MY QUESTION BEGGING IF DENTISTS OR DOCTORS PRESCRIBE OPIOIDS TO THOSE KIDS, EVEN FOR A SHORT WINDOW, ARE THEY MORE LIKELY TO BE, YOU KNOW, DEVELOP ADDICTION LATER IN LIFE. >> YEAH, THAT IS VERY MUCH THE CASE. THIS IS ONE OF THE REASONS WHY CDC NOW WITH THEIR GUIDELINES IS PRACTICES TO LIMIT THE AMOUNT OF OPIOID THT'S BEING OFFERED AFTER WISDOM TEETH EXTRACTED OR SOMEBODY HAS BROKEN A BONE. SOME SUCCESS IS BEING ACHIEVED, NOT NEARLY ENOUGH. I CONTINUE TO HEAR LOTS OF STORIES FROM PEOPLE WHO WENT HOME WITH A BOTTLE OF 30 OXYCONTINS, AFTER HAVING A STRAINED ANKLE. WE SHOULD NOT SEE THAT HAPPENING ANYMORE. FDA IS ALL OVER THIS ALSO TRYING TO BE SURE THAT WE'RE NOT CONTRIBUTING BY THE WAY IN WHICH MEDICINES ARE DISPENSED. MAYBE WE NEED BLISTER PACKS WITH ENOUGH FOR THREE DAYS, THAT'S WHAT YOU WRITE, INSTEAD OF JUST OKAY, WRITE THE PRESCRIPTION, WRITE DOWN NUMBER 30 BECAUSE YOU'RE USED TO DOING IT AND SEND THEM TO THE DRUGGIST. WE HAVE A SERIOUS ISSUE. THERE ARE NUMBERS THERE, INDIVIDUALS WHO HAVE ALREADY TAKEN OPIOIDS FOR ONE WEEK, THE LIKELIHOOD OF GOING ONTO A SIGNIFICANT DIFFICULTY WITH WITHDRAWAL GOES UP PRETTY SUBSTANTIALLY. IT ONLY TAKES A WEEK BEFORE PEOPLE BECOME PHYSICALLY ADDICTED. AND THAT APPRECIATION I THINK IS STILL NOT OUT THERE, IN MANY PRIVATE PRACTICES. >> IT IS A LITTLE AFTER 11:00. ANY LAST PRESSING QUESTION? GO AHEAD. >> THANKS. [LAUGHTER] >> WELL, THANK YOU ALL. [APPLAUSE] >> NOW BACK TO OUR REGULARLY SCHEDULED PROGRAMMING. MICHELLE AND STEVE, WHY DON'T YOU GO BACK UP THERE AND YOU CAN EVEN PUT YOUR SLIDES BACK ON AND LET'S PICK UP WHERE WE WENT OFF UNLESS THERE'S ANYTHING PEOPLE WANT TO DISCUSS ABOUT THIS OPIOID ISSUE. I SEE WE'VE LOST WALTER. DERA, YOU WERE IN THE MIDST OF A QUESTION WITH VARIOUS OTHER POINTS BEING RAISED. >> I HAVE A QUESTION RELATED TO WHAT AMY BROUGHT UP HOW DOES ONE ADVERTISE POSITIONS THAT WERE DIRECTED DO SUBGROUPS OF DEMOGRAPHICS, ALSO INTERESTED IN DETAILS OF WHAT STEVE SAID, DIVERSITY WRIT LARGE, PART OF THE IDEA ABOUT HAVING THREE PEOPLE COME IN, THERE'S SOME SORT OF A CONNECTION AMONG THOSE PEOPLE AND I'M WONDERING WHAT THE NATURE OF THAT WOULD BE IF ONE HAS, YOU KNOW, A PHYSICAL DISABILITY, ONE IS AN ETHNIC MINORITY, ONE IS A WOMAN, I'M JUST INTERESTED IN THINKING OF THAT AND I'M GOING TO ADD ONE MORE THING. HOW LARGE ARE WE WRITING THIS? WE'VE HAD QUESTIONS ABOUT THIS, IN MY OWN DEPARTMENT, ABOUT NATIONAL PEOPLE, TRANSGENDER PEOPLE, HOW ARE WE -- HOW ARE YOU THINKING ABOUT ALL OF THESE MATTERS? >> THIS GROUP HAS GIVEN US THINGS TO THINK ABOUT WHAT WE HADN'T BEFORE, WITH REGARDS TO HOW INITIALLY WE WERE THINKING ABOUT THIS USING DIVERSITY TARGETED POLICY LANGUAGE FROM THE NIH. AND THEREFORE THERE ARE CERTAIN FRAMEWORKS AROUND THAT. YOU'RE PROBABLY FAMILIAR WHEN I SPOKE TO THIS BODY BEFORE I'VE TALKED ABOUT DIVERSITY, RACIAL, ETHNIC, UNDERREPRESENTATION, PERSONS WITH DISABILITIES, AND DISADVANTAGED, THAT CATEGORY DROPS OFF ONCE YOU GET TO THE UNDERGRADUATE, AND THAT'S NIH POLICY. IN TERMS OF WOMEN, YOU CAN INCLUDE WOMEN IN FOAs UNDER THE DIVERSITY POLICY LANGUAGE, BUT ONLY AT THE MORE ELEVATED CAREER STAGES, THEREFORE LIKE ADVANCED POSTDOC AND JUNIOR FACULTY. SO HOW WE'RE THINKING ABOUT DIVERSITY, THAT GLOBAL TERM IT WOULD BE THAT NIH POLICY OF WOMEN, PERSONS WITH DISABILITIES. IN TERMS OF AMY'S FIRST QUESTION HOW A UNIVERSITY COULD DO THAT, THAT'S SOMETHING WE DIDN'T EVEN REALLY THINK ABOUT THAT. WE WERE THINKING ABOUT IT FROM OUR SIDE OF THINGS HOW DO WE PUT OUT AN FOA TO DO THIS TARGETING LANGUAGE. BUT WHEN I SAT DOWN AND LOOKED AT JUST TARGET HIRING AND BIOMEDICINE A FEW UNIVERSITIES WERE USING THAT, TARGET HIRING INITIATIVES. WE HAD A CIRCLE CONVERSATION, THEY ARE PUTTING THE MONEY WITH THE CHAIR OR THE DEPARTMENT AND THEREFORE WHEN THEY DO OPEN HIRES IF THE PERSON HAPPENS TO BE DIVERSE THEN THEY USE THOSE SET-ASIDE FUNDS TO HIRE THAT PERSON. THAT'S JUST A VERY QUICK ANSWER, BUT OBVIOUSLY THAT'S SOMETHING, THAT'S A GREAT POINT THAT WE'LL HAVE TO ALSO THINK ABOUT, BALANCING THE LEGAL SIDE FROM YOUR VANTAGE POINT. DID YOU HAVE ANOTHER -- >> JUST IMAGINING THE CONNECTIONS AMONG INDIVIDUALS, THE AXES OF FULFILLING DIVERSITY REQUIREMENTS. >> I DON'T THINK WE'LL BE PRESCRIPTIVE ABOUT, YOU KNOW, LIKE YOU HAVE TO HAVE ONE FROM EACH BOX, OBVIOUSLY NOT. IT WILL BE THE STRENGTH OF THE SCIENCE AND WHAT'S IN THAT ENVIRONMENT. OUR HOPE IS THAT WE WILL SEE A RANGE OF DIVERSITY VERSUS, YOU KNOW, IT ENDS UP BEING A PROGRAM FOR ALL WOMEN, OR ENDS UP BEING A PROGRAM FOR ALL AFRICAN-AMERICAN OR HISPANIC MEN. WE REALLY DO SINCERELY WANT THIS TO BE A BROAD SPECTRUM OF DIVERSITY. >> ANYTHING ELSE? WE NEED A MOTION TO MOVE FORWARD WITH FLESHING OUT THIS. BEV. SECOND. THIRD. NO, JUST KIDDING. ALL IN FAVOR. I THINK THAT'S EVERYBODY. OKAY. AND SO I'LL JUST STOP. OKAY. THANKS A LOT. >> IF YOU HAVE QUESTIONS, OR COMMENTS, WE HAD HELPFUL ONES, E-MAIL US. E-MAIL ME OR STEVE AS YOU SORT OF THINK ABOUT IT MORE. THANK YOU. >> THOSE BY THE WAY I THOUGHT WERE INCREDIBLY HELPFUL SUGGESTIONS FOR BOTH THOSE TRANSLATIONAL THING AND THE DIVERSITY, WOMEN AND DIVERSITY HIRES. OKAY. SO AT THE LAST COUNCIL WE TALKED ABOUT A POTENTIAL PLAN THAT WE HAD FOR CHANGING THE SPECIAL COUNCIL REVIEW PROCESS. I'LL REFRESH YOUR MEMORY WHAT THAT IS IN A MINUTE. YOU HAD ALL KINDS OF SUGGESTIONS, A FREE AND FAR RANGING DISCUSSION. WE'VE THOUGHT ABOUT THEM A LOT. WE'VE COME BACK WITH SOMETHING THAT WE DID OUR BEST TO TRY TO INCORPORATE WHAT YOUR SUGGESTION, THE BASIC SUGGESTION MADE BY ONE OF YOU AT THE LAST MEETING. WE WANT TO NOW IMPLEMENT THIS POLICY SO WE'RE GOING TO HAVE ANOTHER HOPEFULLY FINAL DISCUSSION AND SEE IF YOU'RE OKAY WITH WHAT WE'RE PROPOSING. ONE THING I JUST WANT TO EXPLAIN WHICH IS WHEN WE DO SPECIAL COUNCIL REVIEW IN CLOSED SESSION, THERE WERE FIVE APPLICATIONS THAT WE'RE GOING TO NEED TO DISCUSSION, YOU NEED TO GO BY THE OLD POLICY. I'LL REMIND YOU WHAT THAT IS. IF WE IMPLEMENT THIS, NIH DOES NOT MOVE AT LIGHTNING SPEED IN MOST CASES. WHAT WE HAVE TO DO IS PUBLISH A NOTICE IN THE GUIDE SAYING HERE ARE THE CHANGES TO THE SPECIAL COUNCIL REVIEW POLICY, AND THEN WE'LL IMPLEMENT THEM FOR APPLICATIONS THAT COME IN AFTER THAT. ONE OF THE REASONS THIS IS IMPORTANT, IT'S UNFAIR TO CHANGE THIS IN MID-STREAM. INVESTIGATORS WHO MIGHT HAVE ALREADY SUBMITTED GRANT APPLICATIONS ABOUT WHICH THERE ARE ISSUES UNDER THE PROPOSED POLICY WOULD BE AT A DISADVANTAGE. HOW DO I -- THERE WE GO. SO I'LL JUST REMIND YOU THAT THE CURRENT POLICY WAS IMPLEMENTED ACROSS NIH, IN 2012. AND ESSENTIALLY THIS IS THE POLICY. I'LL JUST LET YOU READ THAT. AND OKAY, THERE'S A NUMBER OF ISSUES THAT ARE RELEVANT TO THIS POLICY. I DISCUSSED THEM AT SOME LENGTH LAST TIME BUT SINCE FOUR MONTHS PASSED I'M GOING TO GO THROUGH MOSTLY THE SAME FEW SLIDES THAT I SHOWED LAST TIME, JUST TO SET THE STAGE AGAIN. ONE OF THE THINGS THAT HAS INFORMED THIS POLICY IS THIS ISSUE OF HYPER COMPETITION. THIS IS NIH-WIDE DATA, SINCE 2003. YOU CAN SEE THE NUMBER OF APPLICANTS FOR GRANT AWARDS HAS INCREASED FROM, I DON'T KNOW, 55,000, WHATEVER THIS POINT IS, SIGNIFICANTLY, WHILE THE NUMBER OF AWARDS THAT NIH GIVES OUT HAS REMAINED ALMOST CONSTANT, JUST A LITTLE OVER 25,000. NOW, THIS IS NOT A GOOD SITUATION. THIS IS WHAT IS CLASSICALLY DEFINED AS HYPERCOMPETITION. OKAY. IN RESPONSE TO THAT, AND OTHER ISSUES, THERE ARE A LOT OF DIFFERENT IMMINENT PEOPLE WEIGHED IN. THIS IS A PAPER FROM BRUCE ALBERTS AND HAROLD VARMUS AND OTHERS THAT CAME OUT IN 2014, AND HERE'S A QUOTE. AGENCIES SHOULD BE SENSITIVE TO THE TOTAL NUMBER OFS DOLLARS GRANTED TO INDIVIDUAL LABS, DIFFERENT RESEARCH COSTS, WE APPLAUD RECENT DECISION BY NIH TO EXAMINE GRANT PORTFOLIOS CAREFUL BEFORE INCREASING DIRECT RESEARCH SUPPORT FOR LABORATORY BEYOND $1 MILLION PER YEAR. WHAT THEY RECOMMEND HERE IS DIFFERENT FROM EXISTING POLICY, AND EXISTING SCR POLICY WE LOOK AT INDIVIDUALS WHO ALREADY HAVE OVER A MILLION DOLLARS, WHO ARE COMING IN FOR A NEW GRANT APPLICATION. AS I TOLD YOU LAST TIME WE'RE PROPOSING TO ENLARGE THIS TO PEOPLE WHOSE PENDING APPLICATION WILL BRING THEM OVER A MILLION WHICH IS WHAT MOST OF THE COMMUNITY SEEMS TO HAVE RECOMMENDED. FOR EXAMPLE, FASEB, THERE'S 30 OR 40 GROUPS UNDER THE UMBRELLA, RESEARCH RESPONSE SHORES SHOULD MONITOR AMOUNT OF FUNDING GOING TO A SINGLE INDIVIDUAL OR RESEARCH GROUP, THEY PROPOSE LIMITING AMOUNT OF FUNDING AWARDED TO ANY INDIVIDUAL SCIENTIST, WOULD ENABLE MORE PEOPLE TO BE ACTIVELY ENGAGED IN RESEARCH, NIH ANALYSES SHOW LIMITING P.I.'S TOTAL RPG SUPPORT, BLAH, BLAH, BLAH, NUMBERS ARE NOT EXACTLY RIGHT BUT THEY HAVE THE RIGHT IDEA. SO I JUST WANT TO TRY TO DISTILL THE CRITICAL POINT WE GOT FROM THESE AND OTHERS. NIH SHOULD FOCUS NOT JUST ON NUMBER OF GRANTS WE AWARD WHICH IS USUALLY THE METRIC THAT WE LOOK AT, AS OUR BUDGET GOES UP AND DOWN, BUT ALSO ON THE NUMBER OF INVESTIGATORS THAT WE SUPPORT. THIS IS A CRITICAL POINT. AND THE ASSUMPTION, ONE OF THE ASSUMPTIONS, THERE'S VALUE IN A DIVERSE POOL OF IDEAS, RELATED TO WHAT WE JUST FINISHED TALKING ABOUT. OKAY. ANOTHER CONSIDERATION WHICH I THINK GETS SHORT SHRIFT, WE'RE OFTEN FOCUSING ON THINGS LIKE DIMINISHING RETURNS OR HYPER COMPETITION BUT I THINK THESE ARE BOTH INCREDIBLY IMPORTANT VARIABLES. IF YOU HAVE AN INVESTIGATORS WHO IS DIVERSING MINIMAL EFFORT TO FOR EXAMPLE OVERSEEING AN R01, THIS CAN, SOME PEOPLE WOULD SAY MAY NOT ALWAYS BE TRUE, YOU WOULD SAY IN GENERAL THIS CAN NEGATIVELY AFFECT TRAINING ENVIRONMENT IN THAT PERSON'S LABORATORY AND QUALITY OF RESEARCH DONE IN THE LABORATORY. NIH HAS BEEN PARTLY UNDER THE LEADERSHIP OF SHY SILVERBERG, EMPHASIZING INCREASED RIGOR. A NUMBER PROPOSE TO DEDICATE FOR EXAMPLE.8 CALENDAR MONTHS TO AN R01, THIS IS NOT UNUSUAL. I'M NOT QUITE SURE WHERE THAT.8 COMES FROM, IMPLYING THAT PRSON COULD HAVE 12 OR 13 R01s. THINK WHAT YOU WANT BUT A LOT OF PEOPLE MIGHT THINK THAT'S CRAZY. THESE ARE CRITICAL ISSUES IN TERMS OF WHAT WE'RE TALKING ABOUT HERE. THERE'S ALSO I'M NOT GOING INTO DETAIL BECAUSE I DIDN'T REALIZE WALTER WAS GOING TO TALK ABOUT IT BUT IN THE 21ST CENTURY CURES ACT THIS NGRI INITIATIVE WAS INSTITUTED, TO PROMOTE THE DEVELOPMENT OF THE NEXT GENERATION OF RESEARCHERS AND ALSO PROMOTE EARLIER RESEARCH INDEPENDENCE. NOW, THIS IS GOING TO -- THIS INITIATIVE WAS PUT FORWARD QUITE QUICKLY BY NIH, AFTER WHAT HAPPENED WITH THE GSI POLICY WHICH MANY OF YOU MAY REMEMBER. AND IT'S REALLY IN THE PROCESS OF FLUX. FOR EXAMPLE, THE ADVISORY COMMITTEE TO FRANCIS COLLINS MET RECENTLY TO DISCUSS THIS AND THEY HAVE PROPOSED AS WALTER SHOWED ALL KINDS OF MODIFICATIONS TO THIS POLICY, MAKING IT MORE FLEXIBLE, ET CETERA, ET CETERA. BUT THE BOTTOM LINE IS IT'S ALMOST CERTAIN THAT ALL THE INSTITUTES ARE GOING TO BE ASKED TO FUND MORE EARLY STAGE INVESTIGATORS, AND MORE QUOTE/UNQUOTE VULNERABLE INVESTIGATORS. OVERSIMPLIFIED DEFINITION OF WHAT A VULNERABLE INVESTIGATOR IS, A PERSON WHO IF THEY DON'T GET THE R01 THAT'S IN QUESTION THEY WILL HAVE NO GRANT SUPPORT. OKAY. NOW OBVIOUSLY AN ESI DOESN'T HAVE GRANT SUPPORT TO BEGIN WITH LET'S SAY YOU HAD R01, TRYING TO RENEW, JUST BEYOND THE PAYLINE. INSTITUTES WILL BE ASKED TO FUND MORE IN THESE CATEGORIES. WALTER POINTS OUT NINDS WE'RE ONE OF THE LEADING TWO INSTITUTES ACROSS NIH IN TERMS OF SUPPORTING ESIs WE HAD BEEN FUNDING ESIs TEN POINTS BEYOND OUR PAY LINE, IF IT'S 12 WE GO TO 23, OR 22, I FORGET. WE'RE GOING UP TO THE 25th PERCENTILE, WHAT WAS DECREED INITIALLY BY NIH. BUT MORE IMPORTANTLY, WE'RE GOING TO HAVE TO SPEND A LOT MORE DOLLARS FUNDING VULNERABLE INVESTIGATORS. NOW, WE'RE NOT AT LEAST YET AND WE DON'T NECESSARILY ANTICIPATE THIS CHANGING, WE'RE NOT GETTING ANY ADDITIONAL FUNDING FOR THIS INITIATIVE. SO THIS MONEY, THIS IS ALL ONE BIG POT OF MONEY, LIKE THE PAYLINE IS IN THIS POT. SO IF WE'RE FUNDING MORE OF THESE PEOPLE, YOU KNOW, THERE'S ALWAYS -- IT'S ALWAYS NEGATIVELY AFFECTING OTHER GROUPS OF PEOPLE. OKAY. SO THIS LAW SAID WE'RE SUPPOSED TO PAY FOR THE NGRI BY REPRIORITIZING FUNDING BY THE DIRECTORS OF THE NIH INSTITUTES AND CENTERS, AND AS I ALREADY SAID, THIS IS GOING TO BE COSTLY. THIS IS ANOTHER FACTOR THAT AFFECTS THE WAY WE THINK ABOUT THIS WHOLE PROCESS. IT DOESN'T DIRECTLY BEAR ON IT BUT WE NEED MONEY FOR THIS. OKAY. SO I ALREADY SHOWED YOU THIS. LET'S SHIFT GEARS BACK TO THE ORIGINAL SCR POLICY, STILL CURRENTLY IN EFFECT HERE. AND I SHOWED YOU THE SCR APPROVAL CRITERIA HERE FOCUSING ON SPECIAL OPPORTUNITIES AFFORDED TO ADVANCE THEIR RESEARCH, WE'RE FLEXIBLE. RENEWAL APPLICATION IS NOT GOING TO BE A TOTALLY NEW DIRECTION FOR THE INVESTIGATOR. BUT WE HAVE TO CONSIDER VALUE OF CONTINUING A PRODUCTIVE PROJECT. THERE'S OTHER CONSIDERATIONS AS WELL. WE TALK ABOUT THIS IN DEPTH LAST TIME. THESE ARE THE CURRENT SCR APPROVAL CRITERIA, A LITTLE BIT AMORPHOUS. THAT MIGHT BE AN UNDERSTATEMENT. SO THE PROBLEM THAT WE'RE TRYING TO ADDRESS IS THAT THESE CRITERIA AS YOU POINT OUT IN THE DISCUSSION WE HAD ARE QUITE SUBJECTIVE AND DIFFICULT TO APPLY. AND ONE OF THE TESTIMONIES TO THAT, TESTAMENTS, TESTIMONIES? I KEEP MIXING UP THOSE TWO WORDS, IS THAT NINDS HAS DISAPPROVED ONLY TWO APPLICATIONS SINCE 2012. I THINK ACTUALLY SINCE WE MADE THIS SLIDE THERE MIGHT HAVE BEEN ONE MORE WE DISAPPROVED AT THE LAST COUNCIL, EVEN WORSE ACROSS NIH. VIRTUALLY NO APPLICATIONS GET REJECTED IN THE CURRENT SCR PROCESS, THE EXERCISE BECOMES MEANINGLESS. SO IN THE LAST COUNCIL WE PROPOSED TO SOMEWHAT EXTEND THE SCOPE OF THE SCR PROCESS, AS I MENTIONED EARLIER, TO APPLY TO APPLICATIONS THAT CAUSE A P.I. NIH'S SUPPORT TO EXCEED $1 MILLION IN DIRECT COSTS, WE DISCUSSED THAT LAST TIME. WE SAID THAT APPLICATIONS WOULD BE INITIALLY EVALUATED BY PROGRAM STAFF, THEN BY COUNCIL, AND THEN BY THE NINDS DIRECTOR, WE EXCLUDED CERTAINLY CATEGORIES OF RESEARCH MOST PEOPLE AGREE SHOULD BE EXCLUDED FROM THIS ANALYSIS. AND WE DECIDED TO ALSO INCLUDE MULTI-P.I. OR MULTI-COMPONENT APPLICATIONS WHERE ONLY ONE P.I. REACHES THE THRESHOLD. NOW, I'M NOT GOING TO GO THROUGH& ALL THE COMMENTS THAT WERE MADE HERE. OH, WE ALSO PROPOSED VARIOUS CRITERIA. I SHOWED YOU THESE LAST TIME. I'LL MENTION THE PROJECT IS SUPPOSED TO PRESENT AN EXTRAORDINARY -- WE PROPOSED THIS OPPORTUNITY TO ADVANCE A FIELD THAT WOULD NOT OCCUR WITHOUT ADDITIONAL FUNDING TO THE P.I., AND WE ALSO TALKED ABOUT THE PERCENT EFFORT OF P.I., I'LL GET BACK TO THIS IN A MINUTE. NOW, THIS IS AN OVERSIMPLIFIED VERSION OF YOUR FEEDBACK. SO WHAT YOU TOLD US IS THAT DETERMINING IF A PROJECT PRESENTS AN EXTRAORDINARY OPPORTUNITY TO ADVANCE A FIELD CAN BE VERY DIFFICULT AND SUBJECTIVE. A NUMBER OF YOU WERE UNCOMFORTABLE ABOUT HAVING TO MAKE THIS JUDGMENT FOR EVERY SINGLE SCR APPLICATION. WE HEARD THAT LOUD AND CLEAR. ANOTHER ONE OF YOU WHO WILL REMAIN NAMELESS ACTUALLY PROPOSED THAT WE ESTABLISHED A SCORE THRESHOLD, SO WE'RE LOOKING AT APPLICATIONS IN THE PAYLINE, SOMEONE SUGGESTED WE APPLY A THRESHOLD THAT'S LOWER THAN THE PAYLINE, IN THIS PROCESS. SO I'M GOING THROUGH THIS QUICKLY TO LEAVE TIME FOR DISCUSSION BUT THAT IS PRETTY MUCH WHAT WE ARE PROPOSING TO DO. SO WE'RE PROPOSING TO SET A SOMEWHAT FLEXIBLE SCORE THRESHOLD WHICH IS HALF OF OUR PAYLINE, SO RIGHT NOW OUR PAYLINE IS THE 12th PERCENTILE, DIVIDED BY TWO, 6th PERCENTILE. WE'RE PROPOSING IF THE APPLICATION SCORES BELOW THRESHOLD DEFAULT WILL BE TO FUND IT. IT'S HARD TO NOT FUND SOMETHING THAT GOT LIKE A THIRD PERCENTILE IN PER REVIEW. ABOVE THE THRESHOLD THE DEFAULT WILL BE TO NOT FUND. WE DON'T WANT THIS TO BE COMPLETELY RIGID FOR REASONS THAT I'LL EXPLAIN IN A MINUTE. WE'RE GOING TO ALLOW OUR STAFF TO PROPOSE EXCEPTIONS, EITHER SKIPPING WITHIN THIS CATEGORY OR REACHING INTO THIS CATEGORY. WE HOPE THAT THESE ARE EXCEPTIONS AND NOT THE RULE, BY THE WAY WE DID A PILOT EXERCISE THIS ROUND, WHERE WE PRETENDED INTERNALLY THIS POLICY WAS IN PLACE, AND IT WAS KIND OF INTERESTING WHAT RESULTS ARE. I'LL SAY WE'RE VERY FEW PROPOSED SKIPS, FAIRLY LARGE NUMBER OF PROPOSED REACHES. THE STAFF WOULD PROPOSE THESE, THEY WOULD PROVIDE A WRITE-UP JUSTIFYING EXCEPTION TO COUNCIL, YOU WOULD EVALUATE, WE WOULD ONLY TALK ABOUT THE EXCEPTIONS. WE WOULDN'T TALK ABOUT EVERY APPLICATION THAT GOT A SCORE IN THE 6th PERCENTILE, DISCUSS THE ONES WE'RE PROPOSING TO SKIP AND REACH TO. AFTER YOUR FEEDBACK WALTER WILL MAKE THE FINAL DECISION. THERE'S MANY ISSUES I COULD DISCUSS HERE, TRYING TO STAY FOCUSED ON BIG IDEAS AND SIMPLE BUT THIS IS THE CRUX. SO I CAN'T EXHAUSTIVELY EXPLAIN ALL THE POTENTIAL CRITERIA FOR A SKIP OR REACH BUT WANT TO GIVE YOU SOME -- HIGHLIGHT EXAMPLES. WHEN WOULD WE SKIP IN THE 6th PERCENTILE? IF IT OVERLAPS WITH THE P.I.'S EXISTING GRANTS. THAT WAS THE REASON THAT WE REJECTED ONE OF THE SCR APPLICATIONS AT THE LAST COUNCIL. THE OTHER ISSUE WHICH I PERSONALLY WILL DISCLOSE THIS BIAS FEEL STRONGLY ABOUT IS THAT I DON'T -- WE'RE NOT CRAZY ABOUT GIVING A GRANT TO A P.I. WHO IS UNABLE OR UNWILLING TO COMMIT SUFFICIENT EFFORT TO THE APPLICATION. FOR EXAMPLE, THE NUMBERS THAT WE'VE BEEN KICKING AROUND ARE IF IT'S AN R01, THE P.I. SHOULD COMMIT AT LEAST 20% EFFORT. THAT WOULD MEAN A PERSON COULD HAVE FIVE R O 1s, OR 2.5 CALENDAR MONTHS FOR R01. BACK TO THE GSI, UNDER THAT POLICY WE WOULD HAVE ALLOWED FAR FEWER THAN THIS NUMBER OF GRANTS TO A P.I. YES? >> WOULD THAT BE FOR EVERY R01 THE INVESTIGATOR HAS? >> NO, FOR THE NEW ONE, THEY COULD REDISTRIBUTE. THIS IS A COMPLEX DISCUSSION AROUND THE GSI. WE CAN TALK MORE BUT WE DON'T WANT TO APPROVE AN APPLICATION TO WHICH THE P.I. IS PROPOSING .8 CALENDAR MONTHS. >> (INAUDIBLE). >> YEAH, THAT WOULD HAVE TO BE NEGOTIATED WITH THE PROGRAM DIRECTOR, WOULD HAVE TO SAY IT'S APPROPRIATE. THEY HAVE TO HAVE EFFORT TO SPARE IS THE BOTTOM LINE. OKAY. WHEN WOULD WE REACH AGAIN THESE ARE ONLY TWO EXAMPLES. IF THE PENDING APPLICATION ADDRESSES AN URGENT PRIORITY, AND I MEAN TRULY URGENT, OKAY, FOR EXAMPLE THERE'S THE ALZHEIMER'S DISEASE, NAPA INITIATIVE FOR WHICH THERE IS DEDICATED FUNDING, THERE HAD BEEN THE ZIKA INITIATIVE, PERHAPS THE OPIOID CRISIS MAY FALL UNDER THIS, OR THIS IS A LITTLE BIT TRICKIER, OR THE APPLICATION PRESENTS A TRULY EXTRAORDINARY OPPORTUNITY TO ADVANCE THE FIELD. THIS IS THE LANGUAGE YOU SORT OF OBJECTED TO LAST TIME, BUT WE DON'T WANT TO COMPLETELY CLOSE THE DOOR ON THE POSSIBILITY THAT THERE MIGHT BE AN APPLICATION BETWEEN THE 7th AND 12th PERCENTILE COUNCIL THINKS IS SO EXTRAORDINARY WE CAN FUND THIS. WE CAN DISCUSS THIS WHEN I'M DONE TALKING ABOUT THIS. WHEN WOULD WE REACH BEYOND 6th PERCENTILE? IF THE PERSON'S RESEARCH IS INHERENTLY COSTLY, FOR EXAMPLE LET'S SAY THE PERSON HAS NO NIH SUPPORT AND PROPOSE TO BE THE P.I. ON A $2 MILLION A YEAR CLINICAL TRIAL, IT WOULD BE SILLY NOT TO FUND THAT AWARD UNDER THE SCR POLICY ASSUMING WE THINK IT'S OKAY WITH RESPECT TO THE P.I. AND PROJECT. ANOTHER SIMILAR EXAMPLE IF THE APPLICANT IS CURRENTLY THE P.I. ON A BIG EXPENSIVE GRANT, I'M USING A TRIAL AS EXAMPLE, DOESN'T HAVE TO BE A CLINICAL TRIAL, AND PENDING IS R01, A PERSON MIGHT BE A P.I., THE ROLE MIGHT BE ORGANIZATIONAL, THEY ARE NOT GETTING MONEY FROM ALL THE SUBCONTRACTING SITES, BUT THEY ARE PROPOSING TO JUST HAVE A MODULAR R01, SO COUNCIL THAT MIGHT BE AN EXAMPLE WE PROPOSE FOR A REACH. NOW, THIS IS NOT, YOU KNOW, AN EXHAUSTIVE LIST BY ANY MEANS, JUST TO SHOW YOU THE WAY WE'RE THINKING ABOUT IT. ONE THING, IF WE IMPLEMENT THIS POLICY IT WILL BE A PILOT. WE REALLY NEED TO DO THIS FOR A FEW ROUNDS TO LEARN WHETHER THIS IS A GOOD APPROACH OR NOT. OKAY. SO FINAL POINTS, THIS I ALREADY TOLD YOU LAST TIME. I DON'T THINK COUNCIL HAD ANY OBJECTIONS. THESE CATEGORIES OF GRANTS WOULD HAVE BEEN EXEMPTED FROM THE GSI POLICY. WITHIN THE SCOPE OF THE SCR POLICY WOULD BE MULTI-P.I. APPLICATIONS ONLY THE P.I. REACHES $1 MILLION. THERE'S A VERY REAL POTENTIAL FOR GAMING THIS. SO, FOR EXAMPLE, LET'S SAY SOMEONE IS A P.I. ON AN R01, WHICH WILL PUT THEM OVER A MILLION, AND THEY DECIDE JUST TO STICK ANOTHER PERSON ON THE GRANT SIMPLY IN ORDER TO GET IT FUNDED, WHAT WE'RE PROPOSING HERE, WE DISCUSSED THIS LAST TIME, IF IT BRINGS ANY OF THE P.I.s OVER A MILLION, IT WOULD BE SUBJECT TO SCR SCRUTINY. THE REASON WE COULD NEVER IMPLEMENT THIS POLICY IMMEDIATELY IS THAT PEOPLE NEED TO KNOW THIS IN ADVANCE. OKAY. SOME PEOPLE MAY ALREADY BE DOING THIS. AND WE DON'T -- IT WOULD BE UNFAIR TO CHANGE THE RULES. IN ADDITION, THIS IS ANOTHER, ALL THESE ARE COMPLEX BUREAUCRATIC TOPICS THAT WE CAN TALK ABOUT A LOT, BUT WE'RE AT LEAST RIGHT NOW THINKING CONSORTIUM COSTS AND SUBCONTRACTS WILL GENERALLY NOT BE INCLUDED COMPUTING A P.I.'S FUNDING. IF YOU'RE THE P.I., I KEEP USING CLINICAL TRIALS AS AN EXAMPLE BECAUSE THEY ARE EXPENSIVE, IF YOU'RE THE P.I. IN A BIG CLINICAL TRIAL APPLICATION, ONLY A SMALL AMOUNT OF MONEY MIGHT ACTUALLY BE GOING TO YOU, A LOT MIGHT BE GOING TO THE SITES. WE ARGUE IT WOULD BE UNFAIR TO INCLUDE THOSE SUBCONTRACTS TO 20 DIFFERENT SITES IN YOUR BUDGET. CONVERSELY, IF YOU'RE A P.I. WHO WANTS TO BE A CO-P.I., THIS IS NOT MULTI-P.I. BUT CO-P.I. IN SOMEBODY ELSE'S GRANT, YOU'RE COLLABORATING AND DRAWING FUNDS THROUGH A SUBCONTRACT FROM SOMEONE ELSE'S GRANT, WE THINK THAT'S OKAY. THIS COULD BE DEBATED. THIS IS A LITTLE BIT IN THE WEEDS BUT IF COUNCIL WANTS TO DISCUSS IT WE'RE HAPPY TO. AND THEN FINALLY, WE'RE PROPOSING THAT I DIDN'T TALK ABOUT THIS LAST TIME, THERE BE A GRACE PERIOD DURING WHICH A P.I. CAN TEMPORARILY BE OVER A MILLION IN DIRECT COSTS. FOR EXAMPLE IF THIS PERSON HAS EXISTING GRANT THAT WILL END IN THREE MONTHS OF COUNCIL, AND NEW GRANT PUTS THEM OVER A MILLION, WE'RE WILLING TO LET THEM BRIEFLY BE OVER A MILLION IN THIS PERIOD OF TIME. THERE ARE A LOT OF SUBISSUES, I'M HAPPY TO DISCUSS THEM. BY I, I MEAN WE. WE WANT TO STAKE FOCUSED ON THE CRUX, WE'RE MANDATED TO HAVE AN SCR POLICY, AND THE CURRENT POLICY OF DISCUSSING EACH GRANT INDIVIDUALLY AND TRYING TO MAKE THIS JUDGMENT CALL DOES NOT SEEM TO BE WORKING. SO THIS IS THE BEST WE COULD COME UP WITH, AGAIN THE IDEA WAS SUGGESTED BY YOU NOT US, SO ANY GENERAL COMMENTS YOU HAVE THIS IS THE TIME TO DO IT. YES, BRUCE. BRUCE, GORD AND ANOTHER HAND. AND DAVID AND ESAM. REMEMBER THE ORDER. >> I LIKE IT A LOT. THE ISSUE IS IT REACHES IN TERMS OF EXTRAORDINARY RESEARCH, TAKES US BACK TO WHERE WE WERE BEFORE. I WONDER WHETHER 1 TO 6% DOESN'T TAKE CARE OF THAT. BEAUTY IS IN THE EYE OF THE BEHOLDER. >> THIS IS AN IMPORTANT POINT. JUST TO RESTATE WHAT YOU SAID, YOU WOULD GUESS IF SOMETHING IS TRULY EXTRAORDINARY, IT WOULD USUALLY BE CAPTURED IN THIS 1 TO 6% CATEGORY SO WE'RE REINSTATING WHAT YOU TOLD US YOU DIDN'T WANT TO DO LAST TIME. THIS IS AN IMPORTANT POINT. WE COULD ELIMINATE THAT LANGUAGE BUT AGAIN WE WERE A LITTLE NERVOUS ABOUT MAKING IT RIGIDLY CLOSE BECAUSE YOU COULD IMAGINE THAT THERE MIGHT BE AN APPLICATION THAT PEER REVIEW MIGHT UNDERESTIMATED BECAUSE OF A MISUNDERSTANDING AND COULD ARGUE THAT SHOULD BE AN APPEAL BUT AGAIN IT'S SOMETHING THAT GOT A GREAT SCORE SO THIS IS AN IMPORTANT POINT. STEVE, YEAH. >> ONE THING THAT HELPS MAKE IT DIFFERENT, IF THE STAFF IS LOOKING OVER THOSE AND MAKING THE CASE THAT IT'S SOMETHING UNIQUE, A VERY SPECIAL OPPORTUNITY, AND MAKING THAT CASE TO US, THAT THAT HELPS ME RATHER THAN SITTING IN THE ROOM, AND WE'RE JUST DISCUSSING BASED ON SUMMARY STATEMENTS AND WHAT THOSE OF US IN THE ROOM HAPPEN TO KNOW. SO IF STAFF IS PROPOSING A REACH BECAUSE THEY HAVE TAKEN THE TIME TO DIG IN AND CAN EXPLAIN WHY IT'S SPECIAL -- >> THIS IS TRUE BUT YOU HAVE TO REALIZE THAT UNDER THE CURRENT POLICY, STAFF IS PROPOSING TO FUND THE APPLICATIONS THAT YOU'RE SEEING WITH RARE EXCEPTIONS. AND WE HAVE FANTASTIC STAFF BUT PEOPLE TEND TO -- HAVE A TENDENCY TO ADVOCATE FOR THE AREA THEY ARE INVOLVED IN. I UNDERSTAND THE POINT BUT IT'S A SLIPPERY SLOPE. THERE MIGHT BE A LOT MORE PROPOSED REACHES BASED ON WHAT YOU'RE SAYING. AGAIN, THIS IS SOMETHING FOR YOU TO DISCUSS. ESAM AND GORD. >> THE GRACE PERIOD FOR JUST ONE SECOND AS TO HOW THIS MIGHT WORK OUT, THREE MONTHS SEEMS TO BE A LITTLE BIT SHORT TO ARBITRARILY NOT FUND THE GRANT, WHEN THE PERSON WOULD BE ACTUALLY IN COMPLIANCE, ONLY, YOU KNOW, MAYBE YOU WANT TO CONSIDER SIX MONTHS ON THAT, BECAUSE IT REALLY IS A TECHNICALITY IN THE SENSE OF DELAYING THE FUNDING BY A FEW MONTHS TO BRING THE PERSON BACK IN COMPLIANCE. >> OTHER THOUGHTS ABOUT THIS? THE THREE MONTHS I BELIEVE CAME FROM THE GSI POLICY WHERE THE IDEA WAS THAT, YOU KNOW, WE DIDN'T WANT PEOPLE TO GIVE UP A GRANT THAT THEY HAD LIKE A YEAR LEFT ON OR SOMETHING LIKE THAT. THAT REALLY THE TIME WINDOW WAS NOT NARROW, IT BECOMES A GAME SITUATION. >> UP TO SIX MONTHS COULD BE IN ONE OF THOSE THAT ARE DISCUSSED HERE, IF YOU REALLY LOOK AT THE SITUATION WITH SOMEBODY, YOU KNOW, TWO OF HIS OTHER GRANTS ARE GOING AWAY WITHIN THE YEAR. >> YES. THAT'S A REALLY GOOD POINT. WE DO SEE THAT SITUATION. LITERALLY A PERSON ALMOST ALL THE SUPPORT IS GOING TO VANISH IN THREE OR FOUR MONTHS, YOU DON'T WANT THE 60 TO ZERO PHENOMENON. THAT'S A GOOD POINT. I HAVE TO SAY, BOB, THIS WHOLE CONVERSATION, I KNOW THIS INCLUDES YOU, MAKES ME FEEL INCREDIBLY UNCOMFORTABLE. >> OKAY. IS THIS PSYCHOLOGICAL? >> WELL, LET ME BE GRANULAR. YOU KNOW, THIS BEGINS TO SOUND LIKE A DISCUSSION OF THE INHERITANCE TAX. WE SHOULD HAVE NO INHERITANCE TAX, OR WE SHOULD HAVE ONE THAT HITS EVERYONE. BUT YOU'VE PICKED A MILLION DOLLAR MARK AND SAID 20% PER INDIVIDUAL. IF YOU HAVE FIVE R01s, AT A MODULAR RATE, THAT'S 1.25. YOU KNOW WHAT, I KNOW LOTS OF GREAT LABS WHO USE THAT KIND OF MONEY PRODUCTIVELY, REASONABLY, AND I'M MUCH MORE COMFORTABLE WITH THE DECISION TO FUND THEM TO BE PUT IN THE HANDS OF A STUDY SECTION AND NOT IN THE HANDS OF A DECISION. THERE'S TOO MUCH STANDARD DEVIATION IN THE PRIORITY SCORES TO BE SERIOUS THAT A 6% VERSUS 3% VERSUS 8% MEANS ANYTHING. SO I HAVE TO SAY THE WAY I WOULD ARGUE TO DEAL WITH THIS IS PERCENT EFFORT AND NUMBER OF GRANTS AND BASICALLY YES YOU CAN HAVE A HARD CEILING, I THINK ONE MILLION IS A LITTLE LOW. >> OKAY. BY THE WAY, ONE MILLION IDEA IS NOT AN IDEA WE CAME UP WITH. THIS IS AN IDEA THAT WE HEARD FROM THE OUTSIDE WORLD. BUT ANYWAY, YEAH. I UNDERSTAND. HOLLY? >> I THINK I SAID THIS BEFORE. I'D LIKE TO REITERATE, I THINK ONE THING, THE NIH ENJOYS AND EMPHASIZES NEED FOR MULTI-P.I. COLLABORATIVE PROGRAMS, AND I THINK THAT A LOT OF PEOPLE HAVE RESPONDED TO THAT. AND AS A RESULT, WE HAVE MANY MORE APPLICATIONS WHERE BECAUSE OF THESE COLLABORATIONS ONE INDIVIDUAL COMES UP ABOVE THE $1 MILLION LINE AND I THINK ONE NEGATIVE ASPECT OF THIS NEW POLICY IS THAT IT WOULD BASICALLY GO BACK TO HAVING PEOPLE ACT MORE INDIVIDUALLY AND DISCOURAGE THESE COLLABORATIVE PROJECTS. >> THIS IS A GOOD POINT. I SHOULD HAVE CLARIFIED ONE THING. FOR A MULTI-P.I. R01, WE WOULD SPLIT THE COSTS AMONG TO OVERSIMPLIFY THERE THERE'S TWO MULTI-P.I.s AND R01, DIVIDE BUDGET BY TWO, THEY WOULD CONTRIBUTE LESS TOWARDS COMPUTING THE PERSON'S FUNDING THAN A STAND-ALONE R01 BUT I UNDERSTAND YOUR POINT. >> AND THEN THE OTHER COMMENT THAT I WANT TO MAKE IS THAT THE STRENGTH OF THE NIH HAS CONSISTENTLY BEEN THAT THE AWARDS ARE MERIT BASED. AND, YOU KNOW, SOMEBODY WHO IS ASKED TO PARTICIPATE IN A PROJECT AND ENDS UP HAVING A VERY LOW PERCENTILE EFFORT IS PARTLY BECAUSE THEY ARE COLLABORATING WITH OTHER PEOPLE BECAUSE THEY HAVE UNIQUE EXPERTISE. AND THIS KIND OF UNIQUE EXPERTISE MAY NOW HAVE TO BE, YOU KNOW, PRESENTED IN A DIFFERENT WAY OR GAMED AS YOU SAY. >> RIGHT. >> AGAIN ANOTHER COMMENT. >> THAT'S A GOOD POINT. LET'S DISTINGUISH BETWEEN A CO-P.I., LET'S SAY SOMEONE ASKS YOU TO COLLABORATE ON THEIR R01, YOU WON'T BE PENALIZED FOR THAT. THAT WOULD NOT COUNT TOWARDS THIS BUDGET. YOU COULD DRAW FUNDS FROM ANOTHER PERSON'S R01, AND IT WOULD NOT BE INCLUDED WHEN WE'RE COMPUTING WHETHER YOU'RE OVER A MILLION. THE ONLY THING THAT WOULD BE INCLUDED IS IF YOU'RE A MULTI-P.I. GRANT WHERE YOU'RE PLAYING A CO-LEADERSHIP ROLE IN WHICH CASE YOUR FRACTION OF THE FUNDS WOULD BE INCLUDED BUT I HEAR YOUR POINT. DAVID? >> SO I LIKE THE IDEA OF REDUCING THE UNPREDICTABILITY OF THIS, AND SKIPS AND REACHES STILL LEAVE IT UNPREDICTABLE TO PUT IN A TREMENDOUS AMOUNT MUCH TIME AND EFFORT PLANNING A GRANT, THEY MAY HAVE DECIDED TO INELIGIBLE BUT DIDN'T KNOW THAT. THE MORE EXPLICIT AND FEWER AD HOC DECISIONS THAT GET MADE THE BETTER IT IS ALL AROUND. I WAS WORRIED THAT ONE MILLION IS A NICE ROUND NUMBER, WE JUST HEARD EARLIER TODAY THAT THERE WAS 25% INCREASE IN THE COST OF GRANTS. >> RIGHT. >> THAT WERE BEING FUNDED. SO THAT WERE THOUGHT TO BE MERITORIOUS ENOUGH TO BE FUNDED, IF THE NUMBER STAYS THE SAME THE IMPACT WILL CHANGE DRASTICALLY. I DIDN'T REALIZE VALUES WOULD CHANGE THAT MUCH. I DON'T KNOW WHETHER YOU HAVE THE LEEWAY TO SAY IT'S GOING TO BE BASED SOMEWHAT ON THE DISTRIBUTION OF COSTS OF GRANTS OR THE LEVELS OF SUPPORT THAT INVESTIGATORS HAVE HAD IN PRIOR ROUNDS SO THAT IT'S ANCHORED MORE TO REALITY THAN TO JUST A NICE ROUND NUMBER. >> YES. SO THERE'S A COUPLE THINGS. SO FIRST OF ALL, THE OTHER INSTITUTE WHICH HAS BEEN DOING THIS FOR A WHILE AND IS GOOD AT IT IS NIGMS, THEIR LIMIT IS $750,000. THEY ARE A BASIC RESEARCH INSTITUTE WHICH IS DIFFERENT BUT MOST GRANTS WE'RE TALKING ABOUT HERE ARE NOT NECESSARILY INHERENTLY EXPENSIVE SCIENCE, AND IF THEY ARE LIKE A CLINICAL TRIAL WE WOULD PROBABLY MAKE AN EXCEPTION. THE OTHER POINT, WHAT WAS THE OTHER THING I WAS GOING TO SAY? I LOST IT BUT I THINK I'LL REMEMBER SOON. OKAY. DAVID AND THEN THERE'S ANOTHER HAND THAT I CAN'T SEE. IS THAT JANET? >> YES. >> OKAY. >> THIS IS DIFFICULT. SYSTEM, BROUGHT UP BEFORE, IT'S REALLY A MERITOCRACY. GO BACK TO THE SLIDES, IT BOTHERS ME IN PRACTICE AND MESSAGE, THAT WE'RE SENDING A MESSAGE THAT IF THERE'S AN URGENT NIH PRIORITY, THAT TRAINEES AND FUTURE INVESTIGATORS SHOULD FOLLOW THE MONEY, THAT BOTHERS ME AT A MESSAGE. EITHER WE ESTABLISH A CEILING AND PERCENT EFFORT AND SAY THAT REPRESENTS THE BEST SCIENCE WORKING ON IMPORTANT AREAS RATHER THAN HAVE ESCAPE CLAUSES LIKE URGENT PRIORITIES OR -- I WANT TO MAKE SURE WE REMAIN TRUE TO THE MERITOCRACY SYSTEM. >> GOOD POINT. DAVID, I REMEMBERED WHAT I WANTED TO SAY, THERE ARE A NUMBER OF NIH INSTITUTES, MAYBE THE MAJORITY OF NIH INSTITUTES, THAT LIMIT THE INCREASE YOU CAN PROPOSE TO AN EXISTING GRANT. SO FOR EXAMPLE THERE ARE INSTITUTES I THINK NIGMS MIGHT BE ONE WHERE IN YOUR RENEWAL YOU CANNOT ASK FOR MORE THAN 10% MORE THAN WHAT YOU HAVE PRESENTLY. WE HAVE NEVER DONE THAT. SO WE HAVE NOT RESTRICTED INCREASES IN GRANT BUDGETS. DAVID, I THINK THIS IS A GREAT POINT. WHEN WE TALKED -- WHEN I WAS TALKING ABOUT THIS, WE WERE THINKING THIS WOULD BE PRETTY RARE. OKAY? THERE WERE NOT THAT MANY EXAMPLES THAT FELL UNDER THIS RUBRIC. THERE'S ANOTHER PARALLEL DISCUSSION HERE, WHAT IF SOMEONE IS RESPONDING TO INITIATIVE WHICH HAS ITS OWN EARMARKED FUNDING STREAM, FOR EXAMPLE NIH IS GETTING HUNDREDS OF MILLIONS OF DOLLARS ON TOP OF ITS USUAL APPROPRIATION, TO SPEND ON ALZHEIMER'S DISEASE, THE IDEA IS WE DON'T WANT TO RESTRICT THE INVESTIGATORS FROM COMING WITH R01s, AND ALZHEIMER'S AND THIS WOULD NOT BUDGETARILY HURT OTHER PEOPLE, IT FALLS UNDER THE P.I. BANDWIDTH ISSUE. ZIKA WAS A TRANSIENT CRISIS WHERE NIH MOBILIZED. WE PARTICIPATED TO A LIMITED EXTENT. IN A SHORT PERIOD OF TIME WE WANTED TO GET GRANT APPLICATIONS ON ZIKA, IT WAS THOUGHT TO BE A PUBLIC HEALTH CRISIS, WE DIDN'T CARE WHO APPLIED. WE JUST WANTED THE BEST APPLICATIONS. SO I AGREE THAT THE IDEA OF MAKING THIS A SLIPPERY SLOPE WHERE ANYTIME NIH ANNOUNCES SOME INITIATIVE SUDDENLY IT'S EXEMPT FROM THIS PROCESS IS DANGEROUS. YOU KNOW, BUT I GUESS -- >> WE COULD CERTAINLY LEAVE THAT OFF THE MESSAGING. I THINK THAT'S -- IT COULD BE WE COME TO YOU AND SAY THIS ONE DIDN'T FIT BUT WE'RE GOING TO HAVE TO DO IT. >> RIGHT. >> YOU'RE RIGHT. I MEAN, I THINK WE COULD DROP THAT FROM ANY MESSAGING. BUT THAT'S NOT PART OF THE GAME TO LOOK AT. >> YES. AND WE COULD ALSO POTENTIALLY DROP THE TRULY EXTRAORDINARY FROM THE MESSAGING. I'VE HEARD A LOT OF CRITICISM OF THIS AS BEING SORT OF A VESTIGE OF WHAT YOU WERE OBJECTING TO LAST TIME. AS WALTER SAID WE DON'T HAVE TO MESSAGE IT THIS WAY. IF WE REALLY SEE AN EXCEPTION, AND THESE WOULD I THINK BE PRETTY RARE, WALTER TELL ME IF YOU DISAGREE, THEN OF COURSE WE WOULD BRING IT TO COUNCIL AND SAY PEOPLE -- ZIKA IS THIS EMERGING CRISIS, WE NEED TO DO SOMETHING ABOUT IT RIGHT NOW SO WE'LL MAKE AN EXCEPTION. I THINK THAT'S A GOOD POINT. JANET AND AMY. >> BOB, THIS IS TIM. >> YES, TIM. >> I GUESS I'M SUPPORTIVE OF THE APPROACH YOU'RE TAKING, THE 20% CUTOFF MAKES SENSE, I WOULD BUMP UP FROM THE MILLION. MY QUESTION, IS THIS GOING TO TEASE A FINANCIAL GOAL YOU LAID OUT IN THE BEGINNING? YOU CLEARLY SAID WE DO NOT HAVE ENOUGH RESOURCES FOR EVERYTHING THAT'S MANDATED. I MEAN, IF YOU ADOPTED POLICY, IS IT GOING TO HAPPEN ON THE FINANCIAL SIDE? >> OKAY. THAT'S A GREAT QUESTION. OKAY. LET ME SAY A COUPLE DIFFERENT THINGS. SO FIRST OF ALL, WE DID A PILOT EXPERIMENT AS I MENTIONED IN TERMS OF THAT. THIS BY MAKING IT A MILLION, RATHER THAN YOU HAVE TO ALREADY HAVE A MILLION, THAT EXTENDS THE SCOPE SOMEWHAT. AND REMEMBER WE DO HAVE TO DO THIS POLICY. IN TERMS OF HOW MANY FUNDS -- THE PRIMARY MOTIVATION FOR THIS IS NOT FINANCIAL. THE PRIMARY MOTIVATION IS TO INCREASE THE NUMBER OF INVESTIGATORS WE FUND, AND TO EVEN PERHAPS MORE IMPORTANTLY ADDRESS THE ISSUE OF P.I. BANDWIDTH, THE DRIVING FORCE BEHIND THIS. INCIDENTALLY WE'RE GOING TO BE ASKED TO SPEND MILLIONS MORE BECAUSE OF THE NGRI INITIATIVE. WE DON'T REALLY KNOW THE ANSWER TO THAT QUESTION ABOUT WHETHER IT WILL -- TO WHAT EXTENT IT WILL FREE UP MONEY UNTIL WE DO IT. WE DID IT THIS ROUND, AND DIDN'T FREE UP THAT MUCH MONEY TO OVERSIMPLIFY BUT WASN'T A BIG ENOUGH SAMPLE SIZE TO REACH CONCLUSION. IF WE PILOT THIS AND IT DIDN'T MAKE A DIFFERENCE WE CAN GO BACK TO THE DRAWING BOARD. SO WE DON'T REALLY KNOW HOW MANY MORE INVESTIGATORS THIS WILL ALLOW, FOR EXAMPLE, ALLOW US TO FUND. WHO WAS NEXT? >> THANK YOU. >> TIM HAD MY QUESTION. >> WAS AMY NEXT OR LARRY? >> AS WE THINK ABOUT THIS WE HAVE TO REMEMBER SOMETIMES PERFECT IS THE ENEMY OF THE GOOD. AND THERE ARE DEFINITELY GOING TO BE ISSUES WITH THIS BUT AT THE SAME TIME IF WE'RE PRIORITIZING THINGS LIKE INCREASING THE TOTAL NUMBER OF INVESTIGATORS AND ESTABLISHING THAT THE P.I.s HAVE ENOUGH BANDWIDTH TO BOTH DO THE SCIENCE WITH GOOD RIGOR AND PROVIDE TRAINING, WE MAY HAVE TO ACCEPT SOME OF THOSE OTHERS POTENTIAL DOWNSIDES, WHICH AS YOU SAID WILL COME OUT, WILL COME OUT AS YOU DO THE TRIAL PERIOD. AND I DO, I WOULD ENCOURAGE AS FEW CAVEATS AS POSSIBLE, WITH IT. I THINK THAT KEEPING IN PRESENTS OPPORTUNITY TO ADVANCE THE FIELD. ALMOST EVERY INVESTIGATOR WHO HAS A GRANT THAT COMES IN AT SUCH A LOW PERCENTILE FROM WHAT IS UNDOUBTEDLY A VERY ESTABLISHED INVESTIGATOR THAT ALREADY HAS A GREAT AMOUNT OF FUNDING IS GOING TO FEEL LIKE THEY QUALIFY THERE AND I THINK IT MAY PUT THE PROGRAM OFFICERS IN UNIQUELY DIFFICULT POSITIONS. >> RIGHT. >> TO BE ARGUING WITH THE PEOPLE THAT THEY ARE TRYING TO SUPPORT, THAT THIS DOESN'T REPRESENT A TRULY EXTRAORDINARY OPPORTUNITY SO I VERY MUCH AGREE WITH TAKING THAT OUT OF AT LEAST THE MESSAGING. >> RIGHT. LARRY, WERE YOU NEXT? >> YEAH, I THINK THE EXCEPTION THING, IT'S NO DIFFERENT THAN ANY OTHER GRANT. IF YOU HAD A GRANT YOU THOUGHT WAS GOING TO SOLVE THE OPIOID CRISIS AND GOT A LOW SCORE FROM THE STUDY SECTION YOU WOULD DO SOMETHING ABOUT IT. I DON'T SEE THIS IS ANY DIFFERENT. >> INTERESTING BECAUSE WE USED TO HAVE A HIGH PROGRAM PRIORITY PROCESS, HPP PROCESS. WHEN OUR PAY LINE WAS 12, WE USED TO ALLOW PROGRAM DIRECTORS TO NOMINATE FOR SELECT PAY UP TO, SAY, 25th PERCENTILE AND DISCUSS THAT. BECAUSE OF THIS INCREDIBLE BUDGET UNCERTAINTY WE'RE AFRAID TO TAKE ON OUTYEARS. WE HAVEN'T DONE THAT FOR A WHILE NOW. WE'D LIKE TO START AGAIN. WE'VE RECENTLY BEEN GIVEN BRIDGE AWARD BUT YES THAT'S RIGHT. LARRY AND -- >> YEAH. I WANT TO UNDERCORE . >> IS YOUR MIC ON? >> IT'S ON, I'M NOT FACING IT. I WANT TO UNDERSCORE WHAT GORD SAID, MERIT SHOULD BE THE PRIMARY CONSIDERATION, WE DON'T WANT TO COME PRE-MICE THERE. -- COMPROMISE THERE. IT'S DIFFICULT FOR US, SECOND, TO DETERMINE WHETHER AN INVESTIGATOR HAS BANDWIDTH TO COVER WHAT THEY HAVE SAID THEY CAN COVER. DIFFERENT INVESTIGATORS HAVE DIFFERENT BANDWIDTHS, IT'S HARD TO DETERMINE WHAT THAT IS. THE ONLY JUSTIFICATION HERE IF IT FREES UP YOU MONEY TO FUND MOVER INVESTIGATORS, PARTICULARLY JUNIOR INVESTIGATORS, AND I THINK DAVID WAS SAYING WE COULD REALLY DO THIS AS A RETROSPECTIVE STUDY RATHER THAN A TRIAL. WE SHOULD BE ABLE TO HAVE NUMBERS ON HOW MUCH MONEY OVER THE YEARS WE WOULD HAVE SAVED BY IMPOSING THIS LIMIT. >> WE'VE TRIED TO DO THAT. SINCE WE DON'T KNOW HOW THIS POLICY WILL BE INTERPRETED INITIALLY BY A PROGRAM STAFF AND BY YOU IT'S HARD TO COME UP WITH THAT NUMBER. BUT YES WE COULD TALK ABOUT WHAT WE'VE LEARNED LOOKING RETRO SPECK -- RETROSPECTIVELY. FUNDING ESIs 10 POINTS BEYOND THE PAYLINE HAS DROPPED OUR REGULAR PAY LINE BY SOMETHING LIKE 1.5 PERCENTAGE POINTS. THE PAYLINE IS BAD, 12th PERCENTILE, GREAT TO SEE SOMETHING LIKE THIS HAVE POTENTIAL TO RAISE OUR FUNDING PAYLINE. YES TO SOME EXTENT, DOES IT HAVE THE BANG FOR THE BUCK WE'RE HOPING. WHO IS NEXT, STEVE? >> THANKS. >> WALTER, TURN YOUR MICROPHONE ON. >> FIRST THOUGHT ABOUT THIS, MY CRAZY IDEA WAS THAT I WOULD ASK -- I WOULD SAY IF WE FUND THIS GRANT, HERE'S THE PERSON WE DON'T FUND. YOU MAKE THE CHOICE. AND NOBODY WANTED TO DO THAT. BUT IT IS TRUE FOR EVERYTHING WE DO FUND THAT MEANS SOMEONE ELSE DOESN'T GET IT. AND THERE IS A PERSON THERE, YEAH. >> RIGHT. IT JUST DEPENDS WHAT THAT MAGNITUDE IS, RIGHT? >> RIGHT. >> THERE'S ALWAYS GOING TO BE ONE. THERE'S ALWAYS ANOTHER PERSON. >> BUT IT DEPENDS HOW MANY -- YEAH. >> (INAUDIBLE). >> TO TALK ABOUT NIH FLASHY NIH, EVERY INSTITUTE IS DIFFERENT. NIGMS DOESN'T HAVE PAYLINE, THEY LOOK AT EVERY GRANT, FUND, NOT FUND, BREAK INTO SUBGROUPS AND COUNCIL WITH EACH DIVISION. WE COULD OPERATE LIKE THAT. WE DELIBERATELY DECIDED TO BE A FAIRLY HARD PAYLINE INSTITUTE, WE REALIZED THAT COULD BE ARBITRARY, NOT THAT MUCH OF A DIFFERENCE, IF ANY, BETWEEN A GRANT THAT GOT THE 12th AND 13th PERCENTILE, BUT THE QUESTION IS DO WE WANT TO MOVE TO A SYSTEM WHERE WE MAKE JUDGMENT CALLS FOR A LARGE NUMBER OF APPLICATIONS. WHO WAS NEXT? STEVE? >> YEAH, ON THE -- THERE ARE OTHER FACTORS. THAT'S WHY THE COUNCIL IS HERE BESIDES SCIENTIFIC MERIT. WE TALKED ABOUT SOME OF THEM BEING DIVERSITY. THIS IS JUST ANOTHER ONE OF THOSE. IT'S A REDISTRIBUTION. WE CERTAINLY DON'T KNOW IF THE EXTRA GRANT OR GRANTS THAT ARE FUNDED, IF WE DON'T FUND ONE OF THESE, IS TO AN EARLY INVESTIGATOR BUT WE DO KNOW IT'S TO SOMEBODY WHO IS NOT ALREADY FUNDED AT A MILLION DOLLARS. >> RIGHT. >> SO I SUPPORT THIS SORT OF APPROACH, WITH THE OPPORTUNITY TO LOOK FOR EXCEPTIONS AS APPROPRIATE. IN TERMS OF THE -- I GUESS THE ONLY ISSUE I REALLY HAVE IS THE SECOND BULLET POINT UP HERE ON SKIPPING, WHICH IS I THINK THE BANDWIDTH IS VERY IMPORTANT TO CONSIDER AND THAT WE CANNOT ALLOW SOMEBODY TO MANIPULATE THEIR PERCENT EFFORT ON AN EXISTING GRANT JUST TO MAKE THIS ONE MEET 20%. >> YES, THERE'S TWO FLAVORS OF EXISTING GRANTS. THERE'S NINDS GRANTS AND THERE ARE GRANTS FROM OTHER INSTITUTES. THE NINDS GRANTS WE CAN CONTROL, IF THEY PROPOSE LOWERING THEIR EFFORT ON ANOTHER GRANT FROM 10% TO 2% THE PROGRAM DIRECTOR AT NINDS IS NOT GOING TO APPROVE THAT. INSTITUTES DO BUT YES THAT'S A WAY PEOPLE COULD -- >> I THINK THAT NEEDS TO BE A PART OF THE PROCESS THOUGH. >> RIGHT. >> A WAY TO CONTROL OR AT LEAST INFLUENCE OR HAVE THAT DISCUSSION WITH THAT OTHER INSTITUTE. >> YEAH. >> OR TO -- YEAH, I DON'T KNOW. IF THEY ARE NOT GOING TO HAVE THE BANDWIDTH ON THE GRANTS THEY ALREADY HAVE BECAUSE THEY DECREASED ONE FROM 20% DOWN TO, YOU KNOW, 10 OR 5, I THINK WE NEED SOME WAY TO ADDRESS THAT OR -- >> I THINK THAT'S A GOOD POINT. BY THE WAY, I REASON I WROTE E G HERE AS OPPOSED TO 20% IS THAT WE IMAGINE THAT THERE WOULD BE SOME FLEXIBILITY HERE. OKAY. I WOULD TO SOME EXTENT QUESTION THIS IDEA, THE REMARKABLE PEOPLE IDEA, PEOPLE COULD HAVE 20 R01s AND BE FANTASTIC SUPERVISORS. THERE'S PEOPLE WHO COULD HAVE 20 R01s AND GET INCREDIBLE AMOUNTS OF GREAT SCIENCE DONE BUT CREATES A DIFFERENT LAB ENVIRONMENT WHICH ALBERTS AT EL HAVE ARGUED FOR 30 YEARS IT'S NOT HEALTHY, IF THE P.I. DOES NOT KNOW WHAT'S GOING ON IN THE GRANTS SHE OR HE IS SUPERVISING, THAT AFFECTS TRAINING, CREATES A DIFFERENT LAB CULTURE. DAVID? >> I JUST WANTED TO MAKE SURE I'VE UNDERSTOOD AND IF I HAVE BEEN THINKING THROUGH IMPLICATIONS. IF SOMEONE IS GOING TO BUMP UP AGAINST THIS, IF THERE ARE MULTIPLE P.I., CO-P.I., BUT NOT GOING TO BUMP UP AGAINST IF THEY ARE STILL ON THE GRANT DOING THE SAME THING BUDGET THE SAME BUT NOT LISTED AS A CO-P.I., DOES THAT JUST GIVE YOU ANOTHER ROUTE FOR GAMING THE SYSTEM? >> IF THEY PROPOSE -- IF THERE WAS A GRANT APPLICATION THEY ARE PARTICIPATING AS CO-P.I., THEY ARE DRAWING MONEY, YES THEY COULD DO THAT. THAT SEEMS SILLY BUT I'M INTERPRETING WHAT WE PROPOSED HERE. >> I GUESS THEN IT'S A HUMAN PSYCHOLOGY EXPERIMENT. >> THAT'S RIGHT. >> ARE THEY WILLING TO DO THAT TO GET THE SCIENCE DONE EVEN IF THEY DON'T GET TO COUNT THEY'VE GOT THAT MUCH DIRECT SUPPORT. >> ABSOLUTELY A HUMAN PSYCHOLOGY EXPERIMENT. I DON'T KNOW WHAT THE ANSWER WILL BE. I HAVE TO MAKE GUESSES. AMY? >> THAT COULD HAVE AN ADDED BENEFIT. I REMEMBER A COUNCIL ROUND OR TWO IN THE PAST DISCUSSING SOMEONE WHERE THERE WAS A MORE JUNIOR PERSON THAT COULD EASILY HAVE BEEN THE P.I. ON THE GRANT BUT THE SENIOR PERSON HAD CHOSEN TO MAKE HIM OR HERSELF THE P.I., SO THAT MAY NOT BE BAD. THAT MAY ALLOW MORE JUNIOR PEOPLE TO BECOME P.I.s ON GRANTS AND FOR INDEPENDENTS TO HAVE A SECONDARY ADVANTAGE FOR THE MORE SENIOR PERSON WHO MAY BE WORKING WITH THEM. >> NOW, I THINK WE'RE MAYBE REACHING THE END OF THE DISCUSSION. ESAM? >> YEAH, I AGREE WITH THAT CONCEPT, BUT IN REALITY YOU TELL THAT TO THE REVIEWERS WHO KEEP TELLING, YOU KNOW, THE PERSON THAT'S NOT SENIOR ENOUGH WHY IS THE BIG PERSON IN THE LAB NOT THE P.I. WE SEE IT OVER AND OVER AGAIN WHEN WE HAVE A JUNIOR PERSON GO WITH THAT R01 THAT IF YOU COME BACK AND SAY WHY IS THE BIG LAB HEAD NOT THE P.I. >> NOW YOU HAVE AN EXCUSE. >> BY THE WAY, THERE'S SORT OF VERY UNDERLYING BASIC ISSUES UNDERPINNING THIS DISCUSSION. SO FOR EXAMPLE, THERE'S THIS ISSUE OF THE PAYLINE. SO WHEN THE PAYLINE FASEB SAID I REMEMBER JIM GAZELLA SAID HE BELIEVED WHEN THE PAYLINE WAS BELOW 15% YOU START LOSING A GENERATION OF RESEARCHERS BECAUSE THE SMARTEST YOUNG PEOPLE LOOK AT THE FIELD AND SAY LOOK, I HAVE A 1 IN 8 CHANCE OF GETTING AN APPLICATION THAT I SUBMIT FUNDED, I SHOULD MAYBE GO TO MEDICAL SCHOOL OR SOMETHING. THIS PERCEPTION IS A PAYLINE IS TOO LOW THIS IS NOT A VIABLE FIELD FOR THE BEST YOUNG PEOPLE I THINK IS ABSOLUTELY CRITICAL. YOU COULD ARGUE THAT THERE'S TOO MANY PEOPLE IN THE SYSTEM AND THAT'S THE PROBLEM. NOTHING WE CAN DO ASIDE FROM WEEDING THEM OUT BUT PART OF THE MOTIVATION OF THIS THERE ARE A LOT OF PEOPLE ATTRACTED TO DOING NEUROSCIENCE, A LOT ARE ACTUALLY TERRIFIC, AND WE'D LIKE TO BE ABLE TO FUND MORE OF THEM, WHICH MEANS THAT IT'S NOT GOING TO BE A PURE MERITOCRACY. THIS IS NOT A PURIST PROPOSAL. I'M JUST GOING TO ACKNOWLEDGE WHAT DAVE AND A COUPLE OTHERS HAVE SAID. >> BOB, THIS IS TIM. I CAN MAKE AN OBSERVATION? I THINK YOU'RE GOING TO -- THE TEAM HAS DONE A CAPABLE JOB TRYING TO THREAD A COMPLICATED NEEDLE. IT'S REALLY CHALLENGING. I THINK PROBABLY IT'S THE BEST WE COULD THINK OF. LET'S ALL BE CANDID. THE LIKELIHOOD THAT NINDS OR NIH IS GOING TO SEE A DOUBLE DIGIT INCREASE IN BUDGET IS UNLIKELY IN THE NEAR FUTURE SO WE HAVE TO DO THE BEST WE HAVE, NOT LET THE PERFECT BE THE ENEMY OF THE GOOD AND TRY TO CREATE AN ENVIRONMENT THAT IS SUPPORTIVE OF YOUNG INVESTIGATORS WHILE TRYING TO FREE UP RESOURCES. I DON'T KNOW THAT THERE'S A CLEANER WAY TO THREAD THIS, AND WE'LL PROBABLY HAVE TO LOWER THAT AND REVISIT A FEW TIMES. WE PROBABLY DO HOPE TO KEEP A MIND THIS IS ONE TOOL, PERHAPS THE BROADER ISSUE ABOUT THE NUMBER OF SCIENTISTS HAVE TO NOT BE SOLVED THROUGH THIS OTHER MECHANISM BUT OTHER TOOLS. >> THANKS, TIM. LAST QUESTION PERHAPS. LARRY? >> IT'S NOT CLEAR TO ME HOW MANY GRANTS EACH ROUND YOU EXPECT WOULD FLOW INTO THIS CATEGORY. >> OKAY, THIS ROUND I BELIEVE THAT THERE WERE ROUGHLY 20 GRANTS, IS THAT WHAT YOU JUST SHOWED ME, ANNA, THAT FALL INTO THIS CATEGORY? THIS IS A LITTLE COMPLICATED BECAUSE I HAVEN'T EVEN ADDRESSED THE ISSUE BECAUSE I DIDN'T WANT TO GET TOO FAR IN THE WEEDS. HERE WE'RE TALKING ABOUT PERCENTILED APPLICATIONS, THERE ARE ALSO NON-PERCENTILED APPLICATIONS, A WHOLE OTHER DISCUSSION WHICH WE CAN HANDLE INTERNALLY IF THERE'S A TRANSLATIONAL GRANT OR CLINICAL TRIAL WHICH IS NOT PERCENTILED, WE INITIALLY THOUGHT ABOUT HAVING A SCORE THRESHOLD, THERE'S SOME BACK AND FORTH ABOUT THAT, MANY OF THESE NON-PERCENTILE GRANTS WE MAY SHOW YOU INDIVIDUALLY. WE MAY MAKE RECOMMENDATIONS RATHER THAN HAVING A SCORE CUTOFF, EVERY STUDY SECTION IS DIFFERENT, SO I'M GOING TO MAKE UP AN ANSWER APPROXIMATELY RIGHT, THERE MIGHT BE 20 GRANTS IN THIS BASKET, MAYBE EVEN A LITTLE MORE, I IMAGINE YOU DON'T WANT TO DISCUSS ALL THESE INDIVIDUALLY. THE NUMBER THAT WE MIGHT END UP ACTUALLY DISCUSSING WE THINK WOULD BE RELATIVELY SMALL. SO AGAIN THE PROBLEM HERE IS WE ACTUALLY HAVE TO DO SOMETHING, WE'RE MANDATED TO HAVE AN SCR POLICY. WE CAN KEEP DOING WHAT WE DOING WHICH IT'S CLEAR IT'S NOT WORKING. THAT'S WHAT ALMOST ALL OF YOU HAVE BEEN TELLING US. THIS IS A VARIATION ON THAT. ANY ONE LAST QUESTION? I DON'T KNOW IF WE NEED TO VOTE ON THIS. THIS IS NOT REALLY AN INITIATIVE. >> I WOULD SAY IT'S AS CLOSE TO AN INITIATIVE AS WE'RE GOING TO GET. >> SO THEN WHAT WE'RE TALKING ABOUT IS INSTITUTING THIS PROGRAM, WE'LL TRY TO TAKE AS MANY OF THE POINTS THAT HAVE BEEN RAISED INTO ACCOUNT AS POSSIBLE. PERHAPS ALL OF THEM. THESE WERE ALMOST ALL VERY GOOD POINTS. SO WHAT WE'LL COME OUT WITH IF YOU APPROVE IS A MODIFIED VERSION BUT THE CRUX IS ESTABLISHING THIS SCORE THRESHOLD SO WE DON'T HAVE TO DISCUSS EVERY SINGLE -- I DON'T WANT TO USE A CURSE WORD, EVERY SINGLE APPLICATION IN THIS ZONE. SO WHAT'S BEING PROPOSED HERE IS A SCORE THRESHOLD, AND LOWERING THE CAP TO APPLICATIONS AS FASEB AND VARMUS ET AL. SAID TAKEN OVER A MILLION DOLLARS, THAT'S WHAT WE'RE PROPOSING, AND I NEED A MOTION, YAY OR NAY. AMY? >> MOTION TO APPROVE. >> IS THERE A SECOND? ALL IN FAVOR? KEEP YOUR HANDS UP FOR A WHILE. BY THE WAY, KEEP IN MIND THIS IS A PILOT EXPERIMENT, AND WE MEAN THAT. KELLY, TELL ME WHEN YOU HAVE THE -- OKAY. ALL OPPOSED? ABSTENTIONS? I'M BEING HONEST. THIS IS A VERY DIFFICULT SUBJECT. I STRUGGLED TO PUT TOGETHER THIS TALK. AND THIS IS VERY MUCH GOING TO BE SOMETHING THAT WE PILOT AND SEE IF WHAT WE'RE DOING MAKES SENSE, AND FIT DOESN'T LIKE WITHIN FOR EXAMPLE A YEAR WE'RE GOING TO GO BACK TO THE DRAWING BOARD. SO THANKS A LOT. >> WE'LL GET STARTED ON THE AFTERNOON SESSION, LINDA PORTER WHO RUNS THE PAIN POLICY, WILL TALK ABOUT THIS MASTER PLAN AND HAVE FOLKS TALK ABOUT THE INDIVIDUAL COMPONENT. >> THANKS, WALTER. I THINK THIS MORNING BOTH WALTER AND DR. COLLINS GAVE YOU A REALLY GOOD SENSE OF THE URGENCY AND BREADTH OF THE PROBLEM AS FAR AS OPIOID ADDICTION, OPIOID USE DISORDER AND OPIOID DEATHS. THERE'S ANOTHER SIDE, THE ISSUE ABOUT THE NUMBER OF PEOPLE THAT SUFFER WITH CHRONIC PAIN, USE OF OPIOIDS FOR CHRONIC AND ACUTE PAIN AND NEED FOR GOOD ANALGESICS TO HOPEFULLY IN THE NEAR FUTURE BEGIN TO REPLACE SOME OF THOSE WITH SAFER ALTERNATIVE DRUGS. I'M NOT GOING INTO THE MAJOR SCOPE OF THE PROBLEM. IF YOU HAVE QUESTIONS AFTERWARDS, SOME OF US P RESENTING IN NEXT 15 OR 20 MINUTES CAN ANSWER THOSE BUT I'D LIKE TO GO TO WHERE DR. COLLINS LEFT OFF TO GIVE YOU MORE DETAIL ESPECIALLY IN THE COMPONENTS OF THIS MASTER PROJECT AS WALTER CALLED IT WHERE NINDS IS MOST INVOLVED AND WHERE WE NEED YOUR INPUT TO TWO SPECIFIC COMPONENTS OF THE MASTER PROGRAM. TO JUMP IN, THIS PROGRAM IS GEARED BOTH FOR THE OPIOID EPIDEMIC AND PAIN CRISIS AS FAR AS BETTER PAIN MANAGEMENT NEEDS GO. AND IT WAS -- IT EVOLVED OVER MANY, MANY MONTHS OF DISCUSSIONS. IT'S ON A REAL FAST TRACK TO GET THE PROJECT UP AND GOING, HOPEFULLY BEGINNING WITH SOME RESEARCH INITIATIVES IN 2018, IF ALL GOES ACCORDING TO PLAN. SO, ESSENTIALLY THIS IS A PUBLIC/PRIVATE PARTNERSHIP THAT'S BEING ESTABLISHED, THE KEY PLAYERS IN IT ARE THE NIH, INCLUDING PRIMARILY THE NATIONAL NATIONAL INSTITUTE ON DRUG ABUSE AND OUR INSTITUTE AT NEUROLOGY. SO DRUG ABUSE OBVIOUSLY OVERDOSE ADDICTION PIECE, NEUROLOGY MORE RELATED TO THE PAIN PIECE OF THE PROJECT. THE FOUNDATION FOR NIH IF YOU'RE NOT FAMILIAR WITH IT IS A NOT-FOR-PROFIT FOUNDATION SAID UP BY CONGRESS IN 1990, AND THEY ARE -- IT'S A GROUP THAT'S RESPONSIBLE FOR RAISING FUNDS AND MANAGING PROJECTS IN PARTNERSHIP WITH THE NIH. PHARMA AS DR. COLLINS NOTED IS A TRADE ORGANIZATION, ALSO A NOT-FOR-PROFIT, IT'S GOT MEMBERS FROM ACROSS THE PHARMACEUTICAL INDUSTRY, WHO WORK TOGETHER, THE PHARMACEUTICAL MANUFACTURERS AND RESEARCHERS OF AMERICA, ADVOCACY GROUP FOR THE PHARMACEUTICAL INDUSTRY TO MAKE DRUGS -- GET THEM THROUGH TO THE MARKET QUICKER AND MORE EFFECTIVELY. IN THAT GROUP WE'VE GOT INTENSE INTEREST FROM SLIGHTLY MORE THAN 30 PHARMACEUTICAL COMPANIES WHO HAVE BEEN PART OF THE CONVERSATIONS, ALL THROUGH THIS LONG DISCUSSION PROCESS BEGINNING JUNE OF LAST YEAR. SO THE TITLE HERE ENLISTING SCIENCE TO HELP THE OPIOID CRISIS STRATEGY FOR PUBLIC/PRIVATE PARTNERSHIP IS THE RESEARCH PROJECT THAT'S BEEN SET UP IN ITS ENTIRETY. THIS DEVELOPMENT OF THIS PROJECT AND THE TITLE IS THE WHITE PAPER THAT OUTLINES THE ORGANIZATIONAL STRUCTURE OF THE PROJECT, THE RESEARCH COMPONENTS THAT ARE ENVISIONED TO BE PART OF THE OVERALL PROJECT, THE GOVERNANCE OF THE PROJECT AND A BUDGET HAS BEEN DEVELOPED WITHIN THE PROJECT THROUGHOUT THE SERIES OF CONVERSATIONS. SO THE THREE PRIMARY AREAS OF NEED AND THE GOALS OF THE PROJECT ARE RELATED TO BETTER MEDICATIONS FOR ADDICTION TREATMENT, FOR OVERDOSE PREVENTION AND REVERSAL TO PREVENT OVERDOSE DEATHS, AND FOR BETTER ANALGESICS FOR PAIN MANAGEMENT. AND ONE OF THE AGENCIES THAT I ACTUALLY DON'T HAVE LISTED ON HERE AS A KEY PLAYER BECAUSE THEY ACTUALLY HAVE BEEN VERY IMPORTANT TO THE PROCESS AND WILL BE IS THE FDA. OBVIOUSLY ALL THESE MEDICATION DEVELOPMENT PROJECTS HAVE TO BE WORKED OUT WITH THE FDA AS FAR AS ACCELERATING THE REGULATORY PROCESS AS WELL AS THE ACTUAL DEVELOPMENT OF THE DRUGS. SO, I'M GOING TO JUST GIVE YOU A VERY, VERY HIGH LEVEL OVERVIEW OF WHAT THE FULL PROJECT LOOKS LIKE. IT'S MORE OR LESS FOUR DIFFERENT COMPONENTS. WE HAVE FOUR DIFFERENT WORK GROUPS THAT REALLY PARTICIPATED IN THE DEVELOPMENT OF THE WHITE PAPER RELATED TO THESE FOUR AREAS. BUT THEY WORK REALLY DIFFERENTLY AS FAR AS WHAT THE MECHANISMS FOR FUNDING WILL BE AND WHAT INSTITUTES WILL BE THE LEAD. AND SO I'LL GO THROUGH THIS, IT WILL TAKE A FEW MINUTES, AND THEN I'M GOING TO TURN OVER THE PRESENTATION TO THE THREE FOLKS AT NINDS, MICHAEL, AMIR AND CLAIRE WRIGHT, LEADERS IN EACH ONE OF THESE THREE AREAS AND WILL BE LEADING THE NINDS EFFORT THAT IS WITHIN THE OVERALL SO, FOCUSED MEDICATION DEVELOPMENT, DATA AND ASSET SHARING, DATA SHARING AND ASSET REPURPOSING, CLINICAL ENDPOINTS AND BIOMARKERS AND CLINICAL TRIAL NETWORKS ARE THE FOUR MAIN COMPONENTS OF THE PROJECT. THEY WILL EACH BE LED BY DIFFERENT GROUPS SO WE'RE NOT PRESENTING ALL OF THESE IN DETAIL TODAY BUT JUST SO YOU KIND OF UNDERSTAND WHAT THE STRUCTURE LOOKS LIKE, UNDER FOCUSED MEDICATION DEVELOPMENT NIDA'S INTEREST IS PRIMARILY IN ADDICTION TREATMENT, AND IN OVERDOSE TREATMENT. THEY WILL BE THE LEAD ON THAT PIECE, USING FOR THE MOST PART FUNDING MECHANISMS THAT THEY ALREADY HAVE IN PLACE. BUDGET DOLLARS THAT WOULD GO FROM THIS PROJECT WOULD FLOW THROUGH NIDA, MOSTLY WITH EXISTING PROGRAMS THAT WOULD BE EXPANDED. FOR THE PAIN MEDICATIONS, NINDS AGAIN HERE IS THE KEY PLAYER, BUT MOST OF THE ANALGESIC DEVELOPMENT PIECE, THE MEDICATION DEVELOPMENT, WOULD BE DONE THROUGH WHAT THE INDUSTRY IS ALREADY DOING. AND THEIR PROJECTS FOR THEIR PAIN PROJECTS WOULD BE FACILITATED AND ENHANCED THROUGH THE OTHER COMPONENTS OF THIS PUBLIC/PRIVATE PARTNERSHIP. SO AS FAR AS THE DATA SHARING AND ASSET REPURPOSING, THIS ONE IS BEING PRESENTED TO YOU TODAY SORT OF AS AN INFORMATIONAL PIECE OF HOW IT FITS INTO THE MASTER PROJECT, BUT WE WON'T BE ASKING YOU FOR CONCEPT APPROVAL ON IT BECAUSE WE DON'T ANTICIPATE THAT THIS WILL BE USING NINDS OR NIH FUNDS. THIS WILL BE MOSTLY INDUSTRY FUNDS AND ASSETS THAT ARE BROUGHT INTO THAT PIECE. AS FAR AS THE CONNECTION WE'LL BE LOOKING AT SHARE OF DATA AND ASSETS THAT RUN FROM THE PRE-CLINICAL THROUGH THE CLINICAL PIPELINE OF DRUG DEVELOPMENT. CLINICAL ENDPOINTS AND BIOMARKERS, NIDA IS MOST INTERESTED IN CLINICAL ENDPOINTS THAT CAN BE USED IN DEVELOPMENT AND TESTING OF ADDICTION TREATMENTS, AND OVERDOSE USE TREATMENTS, AND AGAIN THEY WILL BE WORKING MOSTLY ON THAT SECTION OF IT. SOME OF IT ON THEIR LEVERAGING RESOURCES THEY'VE GOT AND SOME OF IT BUILT THROUGH THIS PARTNERSHIP. NINDS WILL BE WORKING -- THERE'S IS MORE LOOKING AT ENDPOINTS. FRANCIS MADE A NICE POINT TODAY THE REGULATORY PROCESS FOR GETTING ADDICTION DRUG THROUGH, FOR EXAMPLE, ONE OF THE KEY ENDPOINTS THAT THEY WANT MET IS THE SUSTAINED ABSTINENCE FROM THE DRUGS THAT THEY ARE ADDICTED TO. WHICH IS KIND OF A HIGH HURDLE. SO THEY ARE LOOKING TO BRING IN MORE CLINICALLY MEANINGFUL ENDPOINTS INTO THAT ADDICTION MEDICATION DEVELOPMENT PROCESS. NINDS HAS TWO SPECIFIC AREAS OF BIOMARKER DEVELOPMENT THAT THEY WILL BE RUNNING THROUGH THE PARTNERSHIP. AND AMIR WILL TELL YOU MORE ABOUT THIS IN DETAIL, BUT REALLY FOR SORT OF SPECIFIC AREAS OF BIOMARKER DISCOVERY AND VALIDATION AND THAT'S ON THE PHARMACODYNAMICS VALIDATION AND DEVELOPMENT OF BIOMARKERS FOR PAIN THAT COULD BE PREDICTIVE OF A TREATMENT RESPONSE, WHERE YOU SEE THAT COULD BE INCREDIBLY IMPORTANT TO RUNNING MORE EFFECTIVE AND QUALITY CLINICALLY CLINICAL TRIALS. CLINICAL TRIALS NETWORK, NETWORKS ARE NEEDED FOR BOTH THE ADDICTION MEDICATION DEVELOPMENT AND TESTING AND ALSO FOR THE PAIN ANALGESIC DEVELOPMENT AND TESTING. NIDA HAS NETWORKS ALREADY EXISTING WHERE THEY HAVE BEEN DOING SOME WORK IN THIS ARENA FOR QUITE SOME TIME. SO THEY, AGAIN, WILL BE USING HE PARTNERSHIP TO SORT OF ENHANCE AND EXPAND THEIR EXISTING RESOURCES, WHEREAS NINDS WILL BE HELPING HOPEFULLY WITH NEW RESOURCES TO DEVELOP A PAIN CLINICAL TRIALS RESEARCH NETWORK, WHERE THE INDUSTRY DRUGS CAN BE TESTED THROUGH THE NETWORK, AND NIH CAN RUN DISCOVERY STUDIES THROUGH THE NETWORK, AND ALL THESE PROJECTS WILL BE SOMEWHAT INTEGRATED AS BEST AS POSSIBLE INTO THE LARGE MASTER PLAN. SO I'LL STOP THERE. I THINK IF THERE ARE GENERAL QUESTIONS AT THE END I CAN JUMP BACK IN IF NEEDED BUT I'M GOING TO TURN IT OVER TO MIKE WHO IS RUNNING THE WORK GROUP FOR DATA SHARING AND ASSET REPURPOSING. >> THANK YOU, LINDA. THANK YOU. SO AS LINDA MENTIONED, THIS PORTION OF THE PUBLIC/PRIVATE PARTNERSHIP, THIS PARTNERSHIP BETWEEN MORE THAN 30 INDUSTRY REPRESENTATIVES AS WELL AS THE NIH AND NINDS AS WELL AS NIDA IS FOCUSING ON REALLY LEVERAGING THE KNOWLEDGE THAT'S INSIDE INDUSTRY ASSOCIATED WITH DEVELOPMENT OF DRUGS FOR OPIOID USE DISORDER BUT IN THE CASE OF NINDS, OUR EMPHASIS IS ON LOOKING AT NEW PAIN TREATMENTS NON-ADDICTIVE. SO THE IDEA IS, THE CONCEPT IS, THERE'S A LOT OF PARALLEL EFFORTS THAT HAVE BEEN GOING ON OR CURRENTLY GOING ON INSIDE INDUSTRY, AND THOSE THAT ARE LEADING, LET'S SAY, THE DEVELOPMENT OF VOLTAGE SODIUM CHANNEL BLOCKSERS LIKE NAV 1.7, THE HURDLES OR DIFFICULTY IN DEVELOPING THOSE COMPOUNDS OR THE TRPV1, THERE'S SIDE EFFECTS, IF THOSE ARE SHARED THEN THE COMPANIES CAN MORE EFFICIENTLY USE THE RESOURCES, LIMITED RESOURCES THAT THEY HAVE FOR DEVELOPING COMPOUNDS TO MOVE THEM FASTER TOWARDS APPROVAL. THAT'S THE GOAL HERE, GET THEM TO SHARE DATA NORMALLY PRIVATE BECAUSE THE CURRENT HEALTH CRISIS THAT WE HAVE NOW REQUIRES US TO LOOK AT DRUG DEVELOPMENT IN COLLABORATION AMONG INDUSTRY AND GOVERNMENT IN A DIFFERENT WAY, AND THIS IS CLEARLY IN THE COMPETITIVE SPACE LOOKING AT IT VERY DIFFERENTLY. SO THE OTHER ASPECT OF THIS INITIATIVE IS THE REPURPOSING OF ASSETS THAT MAY HAVE BEEN DEVELOPED FOR OTHER NEUROLOGICAL DISORDERS. FOR INSTANCE, DRUGS THAT ARE USED TO TREAT DEPRESSION CAN ALSO BE USED TO TREAT PAIN, DRUGS USED TO TREAT EPILEPSY CAN BE USED TO TREAT CHRONIC PAIN, WE SHOULD LOOK AT COMPOUND AS NEUROMODULATORS FOR MULTIPLE CONDITIONS. ARE THERE COMPOUNDS DEVELOPED MAYBE THROUGH PHASE 1 AND PHASE 2 AND FAILED FOR EPILEPSY THAT COULD BE REPURPOSED FOR PAIN? WE WANT A SURVEY FROM COMPANIES. AND THEN WE'RE GOING TO HAVE AN OVERSIGHT COMMITTEE THAT WILL PRIORITIZE WHICH ONES WE SHOULD LOOK AT. I WANT YOU TO FOCUS HERE ON THE SECTION OVER HERE TO REALLY LOOK AT WHAT THE GOALS OF THE PROGRAM ARE, IT'S REALLY TO DRIVE FDA APPROVAL FOR NEW MEDICATIONS THAT ARE NOT ADDICTIVE, TO INCREASE THIS COLLABORATION BECAUSE THERE IS A TREMENDOUS AMOUNT OF EXPERTISE IN NIH AND IN INDUSTRY FOR THE DEVELOPMENT OF THESE IF THEY WORK TOGETHER WE COULD BRING THEM INTO THE PATIENTS FASTER. AND ALSO TO INDUCE THE COMPANIES THAT WORK IN THE REALLY HIGHER RISK AREA OF DRUG DEVELOPMENT, THE SMALL BIOTECHS, TO GET THEM TO LOOK AT SOME OF THE REPURPOSING HERE AND TO LEARN FROM THOSE THE DATA THAT WILL BE SHARED FROM BIG PHARMA, SO THAT THEIR PROGRAMS COULD BE MORE PRIORITIZED, AND MOVED EFFICIENTLY. AND THE LAST SLIDE I'M GOING TO SHOW YOU, THIS OVERSIGHT COMMITTEE WHICH WILL BE BUILT FROM REPRESENTATIVES FROM THOSE AT NIH WITH EXPERTISE IN PAIN AS WELL AS INDUSTRY AND THEN REPRESENTATIVES FROM THE FDA TO PRIORITIZE WHICH TYPES OF COMPOUNDS WE SHOULD LOOK AT, AGAIN HERE WE MENTION TRVP1, AND THEN LOOK FOR PARTNERS IN INDUSTRY TO SHARE MORE FOCUSED DATA, AND HOPEFULLY GET THEM WORKING TOGETHER TO DEVELOP NEW MEDICATIONS. THANK YOU. >> SO NEXT PHASE WOULD BE ABOUT BIOMARKERS, YOU'VE HEARD ABOUT THEM SO FAR THROUGHOUT THE DAY. >> EXCUSE ME. I HAVE A QUESTION FOR THE PREVIOUS SPEAKER. >> I'M GETTING ALL THESE SIGNALS, JUST MAKING SURE, I'M SORRY, I SAT DOWN SO QUICK. GO AHEAD. >> I'M WONDERING ABOUT THE FINANCIAL MOTIVATION THAT COMPANIES WOULD HAVE EITHER FOR DATA SHARING OR FOR TRYING TO REPURPOSE A DRUG THAT MAY NOT HAVE MUCH PATENT LIFETIME LEFT? >> SURE. SO THE REPURPOSING IS AN EASY ANSWER. AND THAT'S BECAUSE THE COMPANIES THEMSELVES DON'T HAVE TO PUT IN MONEY. ALL THEY HAVE TO DO A BUILD A LICENSE AGREEMENT WITH SOMEBODY ELSE WHO WANTS TO PUT IN MONEY. THAT'S EASY TO EXPLAIN, WHY THE COMPANIES MIGHT BE MOTIVATED TO GET SOMETHING BACK ON A COMPOUND THAT THEY HAVE PUT A LOT OF MONEY INTO DEVELOPMENT. WHEN IT COMES TO DATA SHARING THIS HAS TO BE AN ALTRUISTIC RESPONSE FROM THE COMPANIES THAT THEY REALLY WANT TO BE TEAM PLAYERS IN DEALING WITH THIS CRISIS OF THE OPIOID USE DISORDER AS WELL AS CRISIS OF CHRONIC PAIN IN THE UNITED STATES. SO THE COMPANIES COULD BENEFIT FROM SHARING DATA TO ACCELERATE THEIR PROGRAMS AND TO ALSO MAYBE STOP A PROGRAM WHICH HAS AN ON-SITE -- ON-TARGET SIDE EFFECT EFFECT WHICH IS UNAVOIDABLE. >> SO SUMMARIZING WHAT DR. COLLINS HAD EARLIER TODAY SAID, WE HAD THREE MEETINGS ON MAIN CAMPUS WHERE WE INVITED THOUGHT LEADERS FROM DIFFERENT SPECTERS TO OPINE. THE BOTTOM LINE, EXTREMELY COMPLICATED. AND BECAUSE OF IT, MANY PEOPLE ARE MOVED AWAY FROM THIS INDICATION OR THEY ARE LOOKING FOR VERY, VERY BIG RETURNS ON INVESTMENT. AND JUST TO OUTLINE HOW COMPLICATED IT IS, IF YOU GO TO THE GUIDANCE DOCUMENT THAT FDA PUBLISHED IN 2014, I WAS GOING TO READ A PART OF IT WHICH WE'LL GIVE YOU AN ESSENTIAL SUMMARY OF THE 35 PAGES. IT SAYS FOR AN OVERALL INDICATION FOR TREATMENT OF CHRONIC PAIN SPONSORSHIP CONDUCT AT LEAST EIGHT TRIALS IN SEVEN CONDITIONS. HOWEVER, WE ENCOURAGE SPONSORS TO STUDY AS MANY CONDITIONS AS POSSIBLE TO FULLY CHARACTERIZE POPULATIONS LIKELY TO BENEFIT FROM THE TREATMENT. ADDRESS IT SQUARE ON. THAT'S WHY BIOMARKERS WE FEEL ARE GOING TO BE THE BEST TOOLS THAT CAN ALLOW US TO DO SEVERAL THINGS. AND JUST TO MAKE A REAL EXAMPLE OF THIS, CYMBALTA, A WELL-KNOWN MEDICATION, HAS FOR APPROVAL WENT THROUGH SEVEN CLINICAL TRIALS, OVER A TOTAL OF 12 PAIN TRIALS. AND VARIOUS DIFFERENT CONDITIONS TO GET APPROVAL. THERE'S A LONG PATH, IT'S QUITE COMPLEX, AND COMPOUNDS LIKE CYMBALTA HAVE SEEN 10 TO YOU 10,000 WHO RECEIVED THE DRUG, 7,000 PLACEBO. WE'RE TRYING TO MAKE THESE TRIALS SMALLER, WE'RE TRYING TO MAKE THE PAIN SCALE MORE MEANINGFUL. AT THE SAME TIME TRY TO ADDRESS THE ISSUE WHICH IS A BIG ELEPHANT IN THE ROOM WHICH IS A PLACEBO CHALLENGE WITH ALL THESE TYPE OF TRIALS. SO ON ALL THOSE THREE FRONTS WE FEEL BIOMARKERS ARE PROBABLY THE BEST TOOLS THAT WE CAN USE TO TACKLE THEM. HERE WE FEEL THIS IS REALLY A GOOD TIME BECAUSE LAST COUNCIL WE TALKED ABOUT THE INITIATIVE THAT WALTER WAS REALLY CHAMPIONING WITHIN NINDS, AND WANTED US TO HAVE. THIS HAS BEEN SOMETHING WE'VE STARTED. AND WE FEEL THIS IS ACTUALLY QUITE EASY MODULE TO ADD ON TO THE EXISTING BIOMARKER INITIATIVE WE STARTED IN 2017. SO AS PART OF THIS WE'RE GOING TO DO THREE THINGS. WE'RE GOING TO ADD ANOTHER MODULE TO OUR EXISTING WORKSHOP THAT'S COMING ON LATER ON THIS YEAR. WE'RE GOING TO USE THE SAME FUNDING MECHANISMS, FUNDING ANNOUNCEMENTS, TO DO THE PAIN WORK. AND WE WILL HAVE NOTICES THAT WILL SPECIFY EXACTLY WHAT WE'RE GOING TO GO AFTER, WHAT TYPE OF INDICATIONS WE'RE LOOKING FOR AND WHAT TYPE OF BIOMARKERS WE'RE LOOKING FOR. AND WE'RE GOING TO ADD ONTO THE CENTRALIZED REPOSITORY OF ALL THE INFORMATION THAT WE HAVE WITHIN NINDS. ON TWO DIFFERENT FRONTS, THE BIG TACKLE HERE IS FOR THE PAIN SCALE, IF YOU LOOK AT THE LEFT-HAND SIDE, YOU HAVE -- YOU'RE DEALING WITH SOMETHING THAT'S A PRIMARY ENDPOINT FOR ALL THE CLINICAL TRIALS, AND WE WOULD LIKE TO GET AWAY FROM THAT. AS PART OF THIS WE'RE PROPOSING VARIOUS OBJECTIVE MEASURES. FOR EXAMPLE, INFORMATION, CONNECTIVITY, MECHANISTIC STRESS LEVELS THAT YOU CAN ACTUALLY MEASURE IN VITRO, AND PERHAPS TRANSMISSION AT THE VERY END. SO WE'RE REALLY LOOKING TO SHIFT THE NEEDLE FROM SOMETHING THAT'S SUBJECTIVE TO SOMETHING THAT'S MUCH MORE OBJECTIVE AND CAN ACTUALLY BE QUANTIFIABLE. TWO FRONTS ON BIOMARKERS, WHICH WE FEEL ARE REALLY IMPORTANT FOR THIS, ARE THE BIOMARKERS THAT ALLOW US TO STRATIFY THE PATIENT POPULATION, TO UNDERSTAND WHICH ONES WOULD ACTUALLY RESPOND TO A TYPE OF TREATMENT, AND ALSO PHARMACODYNAMIC MEASURES TO FIND OUT WHETHER THE TARGET HITS OR SEES THE THERAPEUTIC AND WHAT THE SUBSEQUENT MECHANISMS THERE ARE BEFORE IT ACTUALLY MANIFESTS ITSELF INTO COMPLEX BEHAVIOR. OR COMPLEX FEELING THAT YOU HAVE. SO ON BOTH FRONTS WE CAN DO DISCOVERY, OPTIMIZATION AND VALIDATION ALONG THE LINES I OFFERED TO DO LAST YEAR NINDS-WIDE, THIS WOULD BE A MODULE WE ADD ON TO THAT. >> THANKS. SO IN TERMS OF THE CLINICAL TRIAL ASPECT OF THIS, FROM WHAT YOU'VE HEARD FROM LINDA, MICHAEL AND AMIR, THERE'S A LOT OF CONSIDERATIONS THAT GO INTO BUILDING A CLINICAL TRIAL NETWORK. BUT TAKING A STEP BACK LOOKING AT THE LANDSCAPE, SO REGULATORY APPROVAL OF NOVEL MEDICATIONS FOR PAIN HAS BEEN A BIG PROBLEM BECAUSE OF A NUMBER OF FACTORS THAT I'VE OUTLINED HERE, THE COMPLEXITY AND HETEROGENEITY OF ETIOLOGIES OF PAIN, THE MANY COMORBID CONDITIONS THAT ARE CONCURRENT WITH MANY PATIENTS THAT ARE IN PAIN, AND ALSO THE SAFETY RISKS THAT ARE ASSOCIATED WITH DEVELOPING DRUGS FOR LARGE TARGET POPULATIONS. AND THE OTHER THING IS THAT THERE'S REALLY NO DEDICATED NETWORK FOR PAIN AT THE MOMENT. I MEAN, THERE ARE NETWORKS IN OTHER AREAS, BUT NOT DEDICATED TO PAIN. AND SO ONE OF THE QUESTIONS THAT THE PUBLIC/PRIVATE PARTNERSHIP HAD TO TAKE INTO CONSIDERATION WAS WHAT ARE THE QUALITIES AND CHARACTERISTICS OF AN EFFECTIVE PAIN NETWORK. SO THE ORIGINAL CALL TO ACTION WAS TO DEFINE WELL-DEFINED PAIN CONDITIONS, TO UNDERSTAND WHAT TIMES OF PAIN CONDITIONS WE'RE MOST INTERESTED IN, WERE THEY COMMON, CHRONIC PAIN CONDITIONS, NEUROPATHIC, INFLAMMATORY, ARE WE HAVE YOU HAD IN ACUTE AS WELL AS CHRONIC PAIN, AS FRANCIS TALKED ABOUT EARLIER ONE OF THE BIGGEST CHALLENGES IS THE PRESCRIPTIONS FOR OPIATES AND LARGE NUMBER OF PEOPLE GET IN ACUTE PAIN SETTING SETTING UP FOR ADDICTION PROBLEM LATER ON. SO -- AND THEN AS AMIR MENTIONED, CLARIFYING THE VALUE TO REGULATORY DECISION MAKING, FOCUSING ON SPECIFIC PAIN AREAS. OBVIOUSLY IT'S A TREMENDOUS, TREMENDOUS COST, AND INCREDIBLE BAR TO SURMOUNT, TO RUN MULTIPLE, MULTIPLE TRIALS TO GET ONE DRUG APPROVED. SO THERE HAS TO BE A BETTER WAY. AND SO WE HAD MANY, MANY MEETINGS WITH THE PUBLIC AND PRIVATE PARTNERS. AND CAME TO SOME CONCLUSIONS WHICH OBVIOUSLY WILL BE DEFINED FURTHER AS WE MOVE DOWN THE ROAD AND GET A BETTER CONCEPT OF THE SCOPE THAT'S INVOLVED. BUT ONE OF THE THINGS THAT BECAME CLEAR WAS THE NEED FOR A FOCUS ON PHASE 2 TRIALS THAT WOULD ALLOW US TO DEFINE NEW DRUGS THAT ARE COMING IN OR NEW TREATMENTS COMING IN WITH THE OPPORTUNITY TO BUY UP TO PHASE 3 IN THE NETWORK. OBVIOUSLY, BECAUSE OF WHAT AMIR WAS JUST TALKING ABOUT, THE ABILITY TO BUILD IN BIOMARKER STUDIES WOULD BE CRITICAL, ESPECIALLY IF WE WERE ABLE TO NARROW THE POPULATIONS, AND SOME OF THE EXAMPLES OF THAT ARE IDENTIFYING PEOPLE THAT ARE ACTUALLY GOING TO RESPOND TO A PARTICULAR TREATMENT, NOT MUDDYING THE WATERS WITH HETEROGENEOUS POPULATIONS.& WE ALSO DECIDED THAT IF WE'RE GOING TO SET UP A NETWORK WE HAVE TO BUILD INTO IT THE CAPACITY TO PILOT TEST WITH CERTAIN KNOWN ENTITIES TO MAKE SURE THAT IT'S SET UP PROPERLY AND WORKING PROPERLY, SO THAT WAS ANOTHER PRIORITY. AND THEN THINKING ABOUT HOW -- WHAT WOULD BE THE NECK MECHANISM FOR DOING THIS. AGAIN, THE SCOPE OF THIS IS IS TO SOME EXTENT YET TO BE DETERMINED BUT IN OUR DISCUSSIONS WE HAD, YOU KNOW, MANY DIFFERENT MODELS FOR HOW TO DO THIS. BUT THE ONE WE ARE COMFORTABLE WITH AND MOST FAMILIAR WITH IS SORT OF THE HUB AND SPOKE MODEL, WHERE WE WOULD HAVE DATA COORDINATING CLINICAL COORDINATING CENTERS, BUT IN THIS PARTICULAR AREA WE WOULD HAVE CLINICAL CENTERS OF EXCELLENCE DEFINED BASED ON THE AREAS OF PAIN THAT WE WERE MOST INTERESTED AND THE PUBLIC/PRIVATE PARTNERS WITH MOST INTERESTED IN TARGETING. AND THEN OF COURSE WE DON'T WANT TO REINVENT THE WHEEL SO IF WE HAVE EXISTING NETWORKS, SUCH AS NEURO NEXT, WE HAVE ABLE TO DELIVER NEUROLOGY PATIENTS AND IF THERE ARE NEUROLOGY QUESTIONS, OR EVEN SIREN, OUR ACUTE EMERGING CARE NETWORK, IF THERE WERE TRIALS IN THAT SPACE, STROKE NET, IF YOU'RE TALKING PAIN, WE WANT TO TAKE ADVANTAGE, EVEN NCATS AND CTSAs PROVIDING POTENTIAL PARTNERS FOR IDENTIFYING PEOPLE PARTICIPATING IN THE TRIALS BUT THERE ARE MANY AREAS THAT ARE EXISTING NETWORKS THAT ARE NOT GOING TO BE ABLE TO MEET. SO THE IDEA WOULD BE TO BUILD -- FUND CLINICAL CENTERS OF EXCELLENCE WITH SPOKES GOING OUT IN THE SPECIALTY AREAS, WE WOULD BUILD INTO THE NETWORK THE CAPACITY TO HAVE A PATIENT REGISTRY, WHICH AGAIN IF WE WERE TO DO CLINICAL TRIALS, USING PROSPECTIVE REGISTRIES OR REGISTRIES TO HELP INFORM SOME OF THE TRIALS THAT WE DID, IF WE USED MORE INNOVATIVE MECHANISMS LIKE PLATFORM DESIGNS OR BASKET TRIAL DESIGNS, THAT COULD POTENTIALLY BE INNOVATIVE. AND WE WOULD ALSO BUILD INTO IT BIOMARKER DISCOVERY AND BIOREPOSITORIES. SO THAT'S KIND OF AN OVERVIEW OF THE NETWORK AND THE WAY WE MIGHT SET IT UP. AGAIN, THIS IS SOMETHING THAT THE FUNDING WILL HELP DETERMINE HOW EXTENSIVE THIS WOULD BE. >> OKAY. >> YOU'VE HEARD PROPOSALS FOR TWO CONCEPTS, IS THIS WORKING? THE FIRST IS THE BIOMARKERS PROGRAM FOCUSED ON PAIN, THE SECRETARY IS CLINICAL TRIALS NETWORK. SO QUESTIONS? >> I HAVE A QUESTION, A REALLY BASIC STUPID QUESTION. I GET THAT PHARMA IS GOING TO CONTRIBUTE TO THIS. I GET THAT THE NIH FOUNDATION IS ALSO CONTRIBUTING TO THE FUNDING OF THIS. IS THE NIH PORTION OF THIS COMING FROM THE EXISTENT -- NON-EXISTENT BUDGET? IS THERE A SPECIAL CONGRESSIONAL APPROPRIATION FOR THIS PROGRAM, OR ARE WE TAKING FUNDS FROM EXISTING PROGRAMS TO TRY TO SUPPORT ALL OF THIS GOOD WORK? I CONGRATULATE YOU ON YOUR GOOD WORK, BUT I'M JUST WORRIED HOW WE'RE GOING TO FUND ALL THIS. >> DO YOU WANT ME TO START, WALTER, OR DO YOU WANT TO TAKE IT? >> YEAH, I THINK I BETTER. SO I THINK THAT'S THE MILLION DOLLAR QUESTION. MAYBE MORE THAN A MILLION-DOLLAR QUESTION. SO IN TRUTH, WHAT WE'RE DOING IS TRYING TO GET THINGS, YOU KNOW, ON THE -- YEAH, ON THE RAMP FOR WHEN MONEY COMES. BUT WE DON'T KNOW WHERE THE MONEY'S COMING FROM. THERE IS AN NIH -- AND NIH CAN'T SOLICIT FUNDS FROM INDUSTRY SO NIFH HAS TO SOLICIT FUNDS. THERE'S A FAIRLY DETAILED RESEARCH PLAN THAT'S GOING TO GO TO THE PHARMA GROUP, WHICH COORDINATES ALL THE DIFFERENT PHARMACEUTICAL COMPANIES, AND THEY ARE GOING TO SEE HOW MUCH MONEY THEY CAN PULL IN FROM INDUSTRY SPONSORS. IN TERMS OF WHAT'S GOING TO HAPPEN IN TERMS OF FEDERAL FUNDS, AGAIN, IS UP IN THE AIR. AND THERE HAVE BEEN -- I MEAN WE REALLY DON'T HAVE ANY STRONG SIGNALS OF WHAT'S GOING TO HAPPEN. THERE IS -- THERE WAS ONE SUGGESTION FROM CONGRESS THAT THERE MIGHT BE A LARGE FUNDING TO COME FOR TREATING THE -- SOLVING THE OPIOID CRISIS, WE DON'T KNOW IF THAT'S GOING TO PASS. SO WE'RE REALLY JUST -- WE REALLY -- BECAUSE IT'S A CRISIS WE WANTED TO TEE THINGS UP, BUT WHETHER OR NOT WE CAN DO ANY OF THIS REALLY DEPENDS ON FUNDING. SO I WOULD SAY WITH THE PRESIDENT'S BUDGET WE PROBABLY CAN'T DO ANY OF THIS. WITH THE SENATE BUDGET, WE MIGHT BE ABLE TO DO SOME LEVEL. SO WE'RE REALLY WAITING TO SEE. BUT THE IDEA IS THAT WE REALLY WANT TO PULL THE TRIGGER AS SOON AS WE KNOW. >> I HAVE THE IMPRESSION THAT THERE ARE BASICALLY COMPANIES THAT RUN CLINICAL TRIALS NETWORKS, THEY IDENTIFY PATIENT POPULATIONS AND HOOK UP PEOPLE TO THEM. SO IS THAT TRUE? AND CAN YOU ACCESS THEM AND CONTRACT OUT TO THEM? >> WELL, SO I THINK THAT IS TRUE BUT ONE OF THE THINGS THAT REALLY BECAME CLEAR TALKING TO THE INDUSTRY PARTNERS IS THAT THEY WOULD LOVE TO HAVE A NETWORK THAT COULD DELIVER HIGH-QUALITY PATIENTS AND DO HIGH-QUALITY TRIALS AND THEY DON'T FEEL THAT THEY CAN COUNT ON THEIR CURRENT INFRASTRUCTURE THAT IS OUT THERE TO DO THAT. AND THAT'S SOMETHING THAT WE THINK THAT WE MIGHT BE ABLE TO DO. >> WHY IS THAT THE NIH'S JOB TO DO THAT? >> WELL, WE HAVE A HUGE CRISIS. YOU KNOW, NATIONAL CRISIS IN FRONT OF US. I THINK WE'RE ALL MOTIVATED TO TRY AND SOLVE THAT CRISIS. THAT'S MY ANSWER. >> I WANT TO ADD ONE THING TO THAT. THE VISION BEHIND THE CLINICAL TRIAL NETWORK IS THAT IT WOULD ALSO SUPPORT DISCOVERY STUDIES, AND SO IT WOULDN'T BE COMPLETELY DEVOTED TO TESTING ANALGESICS, BUT ONCE THE NETWORK IS SET UP, ONCE IT'S SET UP, NOT IF IT'S SET UP, I THINK THERE'S A LOT OF POTENTIAL FOR THAT NETWORK TO ALSO RUN FOR EXAMPLE THE BIOMARKER STUDIES, SOMETHING THE CROs THAT INDUSTRY USING ESPECIALLY FOR PHASE 3 TRIALS WOULDN'T REALLY BE ABLE TO MANAGE. >> SO THIS IS JUST A QUESTION. I DON'T KNOW THE ANSWER OR IF ANYBODY KNOWS. NOT TO MINIMIZE RESEARCH BUT THERE'S A SIGNIFICANT SUM OF MONEY EARMARKED EVERY SINGLE YEAR, IS THERE A MECHANISM, HAS ANYONE TAKEN A MECHANISM TO TAKE A RHEOSTAT TO THE FUNDS AND REDIRECT THEM TO A DIFFERENT CRISIS? >> SO I CAN'T DO THAT MYSELF. I DON'T WANT TO GET INTO THE DETAILS BUT MY UNDERSTANDING, I DON'T KNOW IF PAUL SCOTT IS HERE AND CAN SAY I'M WRONG, THE CONGRESS APPORTIONS MONEY TO THE INSTITUTES. AND THE INSTITUTE DIRECTOR HAS THE ABILITY TO REAPPORTION 1% OF THE FUNDS. THAT'S MY UNDERSTANDING OF THE LEGAL STATUS OF REAPPORTIONING. NOW, WHETHER OR NOT THAT'S GOING TO HAPPEN OR NOT, WE'RE HOPEFUL THAT THIS CRISIS IS GOING TO BRING FUNDING TO NIH FOR THIS PURPOSE. MY PERSONAL OPINION IS THAT, YOU KNOW, IF WE DON'T DO IT THIS YEAR, IT'S JUST GOING TO GET WORSE. I MEAN, THIS IS NOT GOING AWAY. SO SOMEBODY, AT SOME POINT, SOMEBODY WILL HAVE TO PULL THE TRIGGER AND WE WANT TO BE READY IS THE WAY WE'RE LOOKING AT IT. I THINK JUST TO HOLLY'S POINT ABOUT THE CROs, SO THE -- I THINK THAT I WOULD EMPHASIZE WHAT CLINTON SAID THAT THE QUALITY OF THE RESEARCH AND THE ABILITY TO DEVELOP INNOVATIVE CLINICAL RESEARCH AS OPPOSED TO DOING THE SAME OLD FAILED THING OVER AND OVER AGAIN IS NOT IN THE CRO SPACE AT THIS POINT. AND -- BUT I THINK THE BIGGER ISSUE WHICH MAY BE IN THE BACK OF EVERYONE'S HEADS IS THAT HOW DOES THE FINANCIAL BENEFIT COME BACK TO NIH IF WE PUT IN ALL THIS EFFORT, HELP THE COMPANY DEVELOP A NEW DRUG THAT THEN THEY MAKE A LOT OF MONEY OFF OF, AND I THINK THAT'S PROBABLY WHAT HELD US BACK IN THE PAST BUT AS CLINTON SAID GIVEN THE SITUATION, PEOPLE ARE WILLING TO TAKE A SHOT AT THIS NOW. AND MAYBE WE JUST DO IT AND GET OUT AND LET THE CROs TAKE OVER ONCE WE FIGURE OUT HOW TO MOVE PAIN THERAPIES FORWARD. >> OKAY. WE'RE SIGNIFICANTLY BEHIND SCHEDULE AND WE HAVE COUNCIL MEMBERS LEAVING EARLY TODAY. COULD SOMEBODY MAKE A MOTION? YOU'VE HEARD THERE COULD BE ZERO DOLLARS FOR THIS, SOME DOLLARS FOR THIS, A LOT OF DOLLARS FOR THIS. I DON'T KNOW EITHER WAY -- WE'RE NOT VOTING ON THAT. >> WE'RE NOT VOTING ON THE MONEY. >> YOU SAY IT SO IT'S RIGHT. >> WE'RE JUST VOTING ON THE MERIT OF ACTUALLY GETTING THESE RFAs IN ORDER, READY TO GO OUT, AND WHAT WE FUND WILL DEPEND ON THE FUNDING SITUATION. >> I MAKE A MOTION. >> ONE SECOND. SO IS THERE ANY OBJECTION JUST IN THE INTEREST OF TIME TO LUMPING THESE TWO TOGETHER IN YOUR -- OKAY. YOU'RE ON, BEV. >> I MAKE THE MOTION TO PARAPHRASE WHAT WALTER JUST SAID, MOVE FORWARD, TEE THESE UP TO BE READY IN THE ADVENT THERE IS FUNDING. >> IS THERE A SECOND? ALL IN FAVOR? THAT'S EVERYBODY. OKAY. THANKS A LOT. ONE LAST -- ONE LAST INITIATIVE CONCEPT, WE'RE ALMOST READY FOR CLOSED SESSION, FRANCESCA BOSETTI IS GOING TO TALK ABOUT THE STROKE PRE-CLINICAL ASSESSMENT NETWORK. >> THANK YOU. I'LL TRY TO BE BRIEF AS MUCH AS POSSIBLE. HOW DO I ADVANCE? THANKS. OKAY. I DON'T WANT REALLY TO CUT THE ACKNOWLEDGMENTS, THIS WAS TRULY TEAM WORK AND WOULD LIKE TO TAKE A MOMENT TO THANK MY COLLEAGUES JIM, DAVE AND ROBERT IN THE DIVISION OF EXTRAMURAL RESEARCH, CHRIS AND OUR DIVISION OF TRANSLATIONAL RESEARCH AND SCOTT, CLAUDIA, CLINTON, AND ALSO NINDS STROKE WORKING GROUP MEMBERS THAT HAVE BEEN INVOLVED IN MANY DISCUSSIONS THAT LED TO THE DEVELOPMENT OF THIS CONCEPT. ACUTE ISCHEMIC STROKE RENDERS BURDEN FOR SOCIETY, LEADING CAUSE OF DISABILITY, FIFTH CAUSE OF DEATH IN THE UNITED STATES, THIRD WORLD WIDE. UNTIL 2015 tPA WAS THE ONLY APPROVED THERAPY, AND DESPITE ITS EFFICACY AND THE FACT THAT IT MADE A DIFFERENCE FOR A LARGE NUMBER OF PATIENTS HAD SEVERAL LIMITATIONS LIKE NARROW THERAPEUTIC WINDOW, RISK OF HEMORRHAGIC TRANSFORMATION AND SUCCESS WITH LARGE CLOTS. IN 2015, SEVERAL TRIALS REPORTED THE SUCCESS OF ENDOVASCULAR THERAPY AS A NEW APPROACH FOR THE TREATMENT OF ACUTE STROKE, AND THIS REALLY COMBINED WITH THE USE OF ADVANCED IMAGING MODALITIES HAS FORMED THIS STANDARD OF CARE AND IMPROVED THE OUTCOME OF PATIENTS. AND INITIALLY THE TIME WINDOW FOR THE USE OF ENDOVASCULAR THERAPY WAS SIX HOURS. DR. KOROSHETZ MENTIONED EARLIER, RECENT TRIALS THAT WERE CONDUCTED, ONE JUST REPORTED LAST WEEK OF INTERNATIONAL STROKE CONFERENCES, THAT OFFERED TOTALLY NEW PERSPECTIVE ON CONCEPT OF TIME IN BRAIN INDICATED THERE IS OPPORTUNITY TO INTERVENE AT LATER TIME WINDOWS UP TO 24 HOURS AFTER THE ONSET OF THE SYMPTOMS, THE TRIAL REPORTED AN IMPROVED OUTCOME IN PATIENTS WITH WAKEUP STROKE UP TO 24 HOURS AFTER THEY WERE LAST SEEN WELL, AND DEFUSE TRIAL ARE INCLUSION CRITERIA, REPORTING SUBSTANTIALLY IMPROVED OUTCOME UP TO 16 HOURS AFTER THE PATIENTS WERE SEEN WELL AND BASED ON THESE RESULTS AMERICAN HEART ASSOCIATION, AMERICAN STROKE ASSOCIATION RECENTLY REVISED THEIR GUIDELINES FOR THE EARLY MANAGEMENT OF ACUTE STROKE PATIENTS. HOWEVER, AS YOU CAN SEE IN THIS FIGURE, THE ACCESS TO ENDOVASCULAR CAPABLE FACILITIES IS A PROBLEM, IS NOT THE SAME ACROSS THE COUNTRY. AND THE FACT THAT NOW WE HAVE AN EXTENDED TIME TO INTERVENE REALLY SUGGESTS THAT PERHAPS IT'S THE TIME TO REVISIT THE POSSIBILITY OF EXTENDING THE TIME WINDOW WITH THE USE OF NEWER PROTECTION, AND ALLOW PATIENTS THAT ARE IN RURAL AREAS OR FAR FROM ENDOVASCULAR CAPABLE FACILITIES TO GAIN ACCESS TO THESE FACILITIES. SO, THE RECENT ADVANTAGE OF ENDOVASCULAR THERAPY OFFERS OPPORTUNITIES TO RECONSIDER NEUROPROTECTION AND NEUROPROTECTANT THAT CAN STABILIZE THE PENUMBRA, THE TISSUE THAT SURROUNDS THE INFARCT BUT IS NOT DEAD YET, OR REDUCE THE RATES OF CORIC EXPANSION MAY OFFER SIGNIFICANT BENEFIT IF GIVEN AS EARLY AS POSSIBLE IN THE STROKE EVOLUTION, AND WE HAVE TO THINK NOT JUST ABOUT THE NEURONS BUT ALSO THINK OUTSIDE THE NEURONS AND COLLATERAL CIRCULATION, COLLATERAL FLOW IS ALSO VERY ATTRACTIVE TARGET THAT WAS EXTENSIVELY DISCUSSED INTERNATIONAL STROKE CONFERENCE AS A WAY TO AFFORD NEW PROTECTION. IF WE LOOK AT THE PREVIOUS TRIALS IN NEUROPROTECTION SUCCESS RATE IS PRETTY MUCH ZERO. BUT WE HAVE TO KEEP IN MIND THAT MOST OF THE PREVIOUS CLINICAL TRIALS ENROLLED 15% OF PATIENTS THAT HAD REPERFUSION, AND HAD ALSO VERY SIGNIFICANT PROPORTION OF SUBJECTS THAT WERE HETEROGENEOUS, SOME ARE SALVAGABLE TISSUE, SOME DID NOT. FROM THE PRE-CLINICAL SIDE THERE WERE PROBLEMS ALSO BECAUSE IT HAS BEEN SHOWN NEUROPROTECTIVE AGENTS TYPICALLY ARE MORE EFFECTIVE IN MODELS OF TRANSIENT OCCLUSION, TRANSIENT ISCHEMIA PERFUSION, RATHER THAN IN PERMANENT ISCHEMIA MODEL, AND ALSO MOST PRE-CLINICAL STUDIES HAVE BEEN CONDUCTED IN SINGLE LABORATORIES OFTEN WITH SMALL SAMPLE SIZE, NOT INDEPENDENTLY REPLICATED, AND REALLY WITHOUT ADHERING TO RIGOROUS PROCEDURES THAT ARE USED IN CLINICAL TRIALS. ALSO, MOST STUDIES USE YOUNG HEALTHY RODENTS THAT REALLY DO NOT REFLECT THE COMORBIDITIES THAT WE SEE IN THE TYPICAL STROKE PATIENT POPULATION. AND ALSO BASED THEIR FINDINGS OFTEN ON INFARCT VOLUME THAT ARE NOT REFLECTIVE OF THE FUNCTIONAL OUTCOME MEASURES THAT ARE USED IN CLINICAL TRIALS. SO, WE HAVE DISCUSSED IN A LOT HOW WE CAN SPAN THE GAP BETWEEN THE PRE-CLINICAL AND CLINICAL SCENARIOS THEN SO ONE APPROACH IS THAT YOU ARE SUGGESTING HERE TO USE A STROKE PRE-CLINICAL ASSESSMENT NETWORK TO FIRST OF ALL TEST THE CONCEPT IF IT'S POSSIBLE TO ACHIEVE NEUROPROTECTION IN A VERY CONTROLLED EXPERIMENTAL SETTING BEFORE INVESTING IN EXPENSIVE CLINICAL TRIALS. AND WE'RE ENVISIONS UP TO SIX LEADING ACADEMIC SITES WITH PUBLISHED EXPERTISE IN THE TRANSIENT MIDDLE CEREBRAL ARTERY OCCLUSION MODEL OF STROKE AND ALSO RELATED COMORBIDITIES TO TEST THE INTERVENTIONS IN PARALLEL, THE MOST PROMISING NEUROPROTECTIVE INTERVENTIONS. AND COORDINATING CENTERS, SIMILAR TO THE WAY IT'S DONE IN CLINICAL TRIALS, WOULD HAVE CENTRAL OVERSIGHT AND PERFORM OVERALL STUDY COORDINATION, STATISTICAL ANALYSIS, RANDOMIZATION BLINDING AND MONITORING OF THE INDIVIDUAL SITES. KEY FEATURES OF THIS NETWORK ARE BUILT-IN REPLICATIONS, TWO SITES WOULD DO THE EXPERIMENTS AT ALL TIME, BUILT-IN ROBUSTNESS BECAUSE EXPERIMENTS WILL BE DONE IN DIFFERENT COMORBIDITIES IF THERE IS A HINT OF EFFICACY FOR A PARTICULAR INTERVENTION OR COMPOUND. SAMPLE SIZE WILL BE REBUST AND WILL BE DETERMINED BY STATISTICAL ANALYSIS BUT JUST TO GIVE YOU AN EXAMPLE OF THE POWER OF THIS NETWORK IF EACH SIDE IS TESTING 20 ANIMALS PER GROUP IN THE SAME TIME FRAME THE SAMPLE SIZE WILL GO TO 120, THAT WOULD TAKE MUCH LONGER TO ACHIEVE AND IT WOULD BE MUCH MORE COSTLY IF A SINGLE SITE WOULD DO THE SAME TYPE OF EXPERIMENTS. WE HAVE THE POTENTIAL TO INCLUDE ONE OR TWO CONTRACT RESEARCH ORGANIZATIONS FOR INDEPENDENT VALIDATION, I MEAN THIS IS NOT REALLY A REQUIRED STEP BUT IT'S SOMETHING THAT WE MAY CONSIDER.& THE APPROACHES COULD BE TIME AND COST EFFECTIVE, USE ADAPTIVE DESIGN SO THAT INTERVENTIONS AS I MENTIONED ARE TESTED IN PARALLEL BY IF SOMETHING SHOWS THAT IS NOT REALLY EFFICACIOUS WE CAN DROP IT OUT EARLY FROM THE TESTING, AND INVEST MORE IN INTERVENTIONS THAT SHOW EFFICACY AND INCREASE THE NUMBER OF COMORBIDITIES OR POSSIBLY ADD ANOTHER SPECIES. THERE WOULD BE COORDINATING CENTERS, AS I MENTIONED, AND STEERING COMMITTEE WITH REPRESENTATION FROM BASIC SCIENTISTS, CLINICAL SCIENTISTS AND INDUSTRY TO HELP MOVE THIS FORWARD TO CLINICAL TRIALS THROUGH STROKE NET. THIS IS JUST SCHEMATIC REPRESENTATION OF THE NETWORK. YOU SEE THERE ARE UP TO SIX SITES, AND POTENTIALLY CRO, AND IF YOU TAKE THESE FIRST WE WOULD START TESTING THINGS IN YOUNG MALES AND FEMALES, AND THEN ADD MODELS OF AGING, AS WELL AS HYPERTENSION, WHICH IS ONE OF THE MAJOR RISK FACTORS IN THE STROKE PATIENTS, DIABETES GIVEN IN COMBINATION WITH tPA OFTEN USED IN ACUTE SETTING OF STROKE PATIENTS AND IF THINGS REALLY LOOK PROMISING WE COULD CONSIDER USING A SECOND SPECIES. NOW, THIS IS NOT NECESSARILY ALL THE THINGS THAT WE'LL BE DOING BUT TO GIVE AN IDEA OF POTENTIAL AND COMPLEXITY OF THE NETWORK. THE PROCESS THAT WE PROPOSE IS TO HAVE ONE RECEIPT DATE, SO THAT ALL PROPOSED INTERVENTIONS ARE TESTED, REVIEWED AT THE SAME TIME AGAINST EACH OTHER. AND THE REVIEW WOULD OCCUR THROUGH NINDS STUDY SECTION, THAT WOULD SELECT THE COORDINATING CENTER AS WELL AS THE TOP SIX SCORING APPLICATIONS THAT WILL BECOME THE NETWORK SITES. INVOLVEMENT OF THE STEERING COMMITTEE AND EXTERNAL ADVISORY BOARD IN THE PROCESS, AND COUNCIL WOULD REVIEW AND APPROVE THE SIX INTERVENTIONS THAT ARE SELECTED, AND AWARDS WOULD BE MADE FOR UP TO THREE YEARS, HOPEFULLY IN TWO YEARS WE'LL BE ABLE TO GET RESULTS. AND IN PHASE 2 IN THE MEANWHILE WE'LL GET INFORMATION THROUGH REQUEST OF INFORMATION FROM THE BROAD SCIENTIFIC COMMUNITY AND PHARMA TO GET ADDITIONAL CANDIDATES THAT COULD BE TESTED THROUGH THE NETWORK, AND THEN MAKE THE AWARD TO THE SITES. SO I THINK I'LL STOP HERE. I WANTED TO SAY THAT THIS CONCEPT IS RESPONSIVE TO A NUMBER OF PLANNING EFFORTS AND WORKSHOPS THAT NINDS HAS ORGANIZED AS WELL AS THE EXTERNAL COMMUNITY, PARTICIPANTS IN THE RECENT STROKE TREATMENT ACADEMIC INDUSTRY ROUNDTABLE PLACED A HIGH PRIORITY ON EVALUATING AGENTS THAT COULD IMPROVE OUTCOME FOLLOWING ENDOVASCULAR THERAPY BUT ESTABLISHING THE MOST PROMISING AGENTS THAT COULD BE TAKEN TO CLINICAL TRIALS IS AN IMPORTANT FIRST STEP AND COULD SAVE A LOT OF MONEY BEFORE MOVING TO CLINICAL TRIALS. SO THANK YOU. I SEE BOB IS SIGNALING ME. I'M HAPPY TO TAKE ANY QUESTIONS. >> OKAY. QUESTIONS? AGAIN, WE DON'T NECESSARILY NEED TO FOCUS ON THE DETAILS BUT IT'S THE CONCEPT THAT WE'RE ASKING ABOUT, OVERALL CONCEPT. ESAM, DID HAVE YOU YOUR HAND UP? I'LL ERR ON THE SIDE OF YOU'RE NEXT. >> THIS IS OUTSTANDING. IN MANY WAYS, I WONDER WHY WE HAVEN'T DONE MORE OF THIS BEFORE. THE IDEA OF A COMMON PHENOTYPING CORE, IF YOU WOULD, THAT REALLY IS RUNNING ANIMAL MODELS IN A CONSISTENT WAY, AND STATISTICAL WAY HAS WORKED IN OTHER DISEASES FUNDED BY THE NIH, I THINK STROKE RESEARCH IT'S AMAZING. MY ONE SUGGESTION FOR YOU TO CONSIDER IS TO SEE WHAT CAN EMERGE FROM THIS TYPE OF NETWORK IN TERMS OF BIOMARKERS AND EARLY TRANSLATIONAL OPPORTUNITIES. SO MAYBE BUILD INTO THIS SOME MECHANISM TO USE SOME OF THE ANIMAL DATA, EITHER TRANSCRIPTOMICS OR ANY ELSE THAT EMERGES FROM THESE EXPERIMENTS TO ENCOURAGE BIOMARKER DEVELOPMENT AT THE SAME TIME AND VERY EARLY. >> DERA? >> IN THE DIAGRAM YOU HAD THAT THE MALES AND FEMALES TESTED AT DIFFERENT SITES WAS THAT JUST CONVENIENCE FOR SCHEMATCS OR WOULD ONE GROUPING DOING MALES, ANOTHER DOING FEMALES? >> NOT NECESSARILY. I MEAN, THESE ARE DETAILS THAT WE'LL FIGURE OUT, BUT JUST TO GIVE YOU THE VISUAL IMPRESSION THAT THINGS WILL BE TESTED IN TWO DIFFERENT LABORATORIES AT THE SAME TIME FOR THE INDEPENDENT REPLICATION. >> I SEE. NO, IT MAKES SENSE TO TEST THEM BOTH. IT SEEMED IF YOU FOUND DIFFERENCES BETWEEN MALES AND FEMALES THAT WERE TESTED AT DIFFERENT SITES YOU MEETLY WOULD TO SEE IS IT A DEVICE DIFFERENCE OR SEX DIFFERENCE SO I WAS -- >> WE'RE NOT JUST HAVING MALES TESTING THE MALES. >> THAT TOO. NO, OTHER THAN THAT, I JUST NOTICED THAT. >> OKAY. >> I AGREE THIS SOUNDS LIKE A GREAT IDEA. IT SOUNDS SIMILAR TO MY UNDERSTANDING OF WHAT MULTI-PART DID. SO CAN YOU TALK ABOUT HOW YOU MIGHT LEVERAGE THE SUCCESSES AND/OR THE, YOU KNOW, CHALLENGES THAT MULTI-PART FACED AND HOW THIS MIGHT BUILD UPON THAT? >> YEAH, THAT'S A GREAT POINT. I WAS IN THE EXTERNAL ADVISORY BOARD FOR MULTI-PART, AND SO I ATTENDED ALL THEIR MEETINGS. AND FIRST WE WERE INFORMED BY THEIR PROCESS IN THESE, SOME DIFFERENCES THAT WE HAD FROM THE MULTI-PART IS THE USE OF LONG-TERM FUNCTIONAL OUTCOME. THEY WERE MAINLY FOCUSING ON INFARCT VOLUME AS OUTCOME, ALSO THERE WAS NOT REALLY A LOT OF DISCUSSION ABOUT COMORBIDITIES THAT ARE CRITICAL ASPECTS OF THESE BUT LIKE THE COORDINATING CENTER IDEA IS DEFINITELY SOMETHING THAT WAS SO VERY VALUABLE FROM THAT EFFORT. >> WILL YOU BE FOLLOWING UP POTENTIALLY ON COMPOUNDS INITIALLY TESTED MULTI-PART SINCE IT SOUNDS LIKE YOUR TESTING IS MORE EXTENSIVE? >> MULTI-PART DIDN'T TEST FUNDING TO TEST, THEY GOT FUNDING FOR PLANNING. AND SO I MEAN WHAT WE COULD POTENTIALLY DO IS TO RECONSIDER THINGS THAT WERE TESTED IN CLINICAL TRIALS PREVIOUSLY AND FAILED OR THINGS THAT THE INDUSTRY WAS STARTING TO DEVELOP, BUT THEY DROPPED WHEN EVERYBODY RAN AWAY FROM NEUROPROTECTION. THAT'S WHY WE REALLY HOPE TO ENGAGE PHARMA IN THIS EFFORT. >> ANYTHING ELSE? OKAY. THEN WE NEED A MOTION ABOUT WHETHER TO MOVE AHEAD WITH THIS CONCEPT. OKAY. SECOND. ALL IN FAVOR OF ENDORSING THE CONCEPT? ALL OPPOSED? GORD? >> I'M NOT OPPOSED. >> OKAY. >> SORRY. >> OKAY. >> (INAUDIBLE). >> OKAY. AND I DIDN'T SAY ABSTENTIONS. OKAY. BEFORE WE GO INTO CLOSED SESSION, SO THIS IDEA YOU BROUGHT UP AT THE BEGINNING OF THE MEETING, A FEW PEOPLE CAME UP TO ME OF BEGINNING A DISCUSSION OF THINGS YOU'D LIKE TO SEE ON THE OPEN SESSION AGENDA. ONE THING THAT WILL CERTAINLY BE ON THE OPEN SESSION AGENDA IS THIS NGRI INITIATIVE, WHAT WE'RE DOING ABOUT FUNDING MORE ESIs, VULNERABLE INVESTIGATORS, THAT WILL DEFINITELY BE ON IN ONE FORM OR ANOTHER. AND I UNDERSTAND THAT WE'RE SORT OF BLIND SIDING YOU HERE BUT ARE THERE ANY IDEAS FOR THINGS YOU MIGHT WANT TO SEE DISCUSSED AT THE OPEN SESSION? GORD? >> IT WAS CLEAR WE HAD GREAT DISCUSSION ABOUT THE WHOLE QUESTION HOW TO DEAL WITH THE MILLION DOLLAR AND ABOVE ONE. OVER LUNCH, I GOT INTO A DISCUSSION WHERE ONE OF THE POINTS THAT WAS RAISED AND GOT RAISED THIS MORNING AS WELL WAS THE POINT THAT ONCE YOU GET BELOW THE 10% LEVEL, I THINK ANYONE WHO HAS BEEN ON STUDY SECTION KNOWS THE NOISE LEVEL JUST GETS ENORMOUS, AND THINGS GET REALLY UNPREDICTABLE AND PERHAPS VERY POORLY DECIDED. SO ONE IDEA WHICH I THINK IS WORTH DISCUSSING IS THE IDEA OF KIND OF PUSHING WHAT OUR FEARLESS LEADER WAS ROOTING FOR, A 15% PAYLINE. >> ACTUALLY HE'S OUR FEARLESS LEADER. >> THAT'S WHO I WAS REFERRING TO. NO, HE ACTUALLY TALKED -- >> I'M NOT CONFUSED. >> NEVER MIND, OKAY. >> YEAH. I'M LOOKING IN THAT DIRECTION. >> THE IDEA OF HAVING A MINIMUM PAYMENT. >> MINIMAL PAYLINE, A LOT OF MOVING PIECES TO THAT, BUT AT LEAST FROM THE DISCUSSION I HAD WITH A FEW PEOPLE AND MY PERSONAL SENSE IS ALMOST ANYONE WOULD RATHER ACCEPT A CUT IN THEIR GRANT THAN NO GRANT, AND I THINK THAT'S JUST A MUCH MORE WORKABLE THING, WORTHY OF OUR DISCUSSION. SO IF PEOPLE ARE INTERESTED, I WOULD PUSH FOR THAT DISCUSSION. >> OKAY. SO ARE YOU GETTING THIS? THE IDEA IS TO DISCUSS WHETHER WE WANT TO SET A MINIMAL PAYLINE AND IF SO, WHAT WILL WE DO TO MAKE SURE WE COULD MAKE PAYMENT. OKAY. DAVID? >> SO ONE OF THE THINGS THAT YOU AND I HAD E-MAILED ABOUT OFFLINE WAS APPARENTLY THERE HAD BEEN SOME DISCUSSION ABOUT THE FUTURE OF THE PHYSICIAN-SCIENTIST, THE PIPELINE, WORK AT NINDS, COULD THAT BE PRESENTED SO WE COULD BE BROUGHT UP TO DATE ABOUT WHAT INITIATIVES ARE -- >> I HAVE NO MEMORIAL RIF -- MEMORY OF THAT BUT WE CAN DO IT. >> IT WAS WITH WALTER, WASN'T IT? IT WAS WITH BOB. THAT'S WHY YOU HAVE NO MEMORY OF IT. IT WAS THE MULTI--- THE TRANS-NIH WORKING GROUP. >> OH, OKAY. >> DELIBERATIONS THAT THEY HAD REGARDING HOW BEST UPON TRAINING FOR PHYSICIAN-SCIENTISTS IN THE ROLE OF PHYSICIAN-SCIENTISTS. >> WE CAN PUT THAT ON THE AGENDA. THE REASON WE TRY TO GET THESE IN ADVANCE, WE USUALLY TRY TO DO SOME LEG WORK, ANALYSIS FROM BEFORE AS OPPOSED TO SUDDENLY DISCUSSING IT. ANYTHING ELSE? OKAY. IN THE INTEREST OF TIME IF YOU HAVE SUCH IDEAS E-MAIL US. YOU CAN SEND THEM TO ME AND I'LL DISBURSE THEM. WE WANT YOUR INPUT ABOUT THINGS YOU WANT TO TALK ABOUT IN ADDITION TO A FEW THINGS WE HAVE TO TALK ABOUT. I REALLY ENCOURAGE YOU TO DO THAT. >> TO THE POINT OF THE ANALYSIS WORKING GROUP, TAYLOR AND CHRISTINE TORBORG ARE GOOD AT GOING THROUGH DATA, SO IF THERE ARE THINGS THAT WOULD BE HELPFUL WE'LL BE -- THEY WOULD BE HAPPY TO HELP. GOOD. >> OKAY. SO IF THERE'S NOTHING ELSE, WHY DON'T WE TAKE A 5- TO 10-MINUTE BREAK AND GO INTO CLOSED SESSION.