>> WE'RE GOING TO ENDEAVOR TO FINISH THIS AFTERNOON BY 3:30. THE OPEN SESSION OF COUNCIL IS OPEN TO THE GENERAL PUBLIC, TO ATTEND IN PERSON AND IT IS BEING LIVE VIDEOCAST. FOR THOSE COUNCIL MEMBERS ATTENDING AT YOUR PLACE IS A FOLDER THAT CONTAINS INFORMATION ABOUT THE OPEN SESSION INCLUDING AGENDA AND ROSTER. I WOULD REMIND THE COUNCIL MEMBERS HERE IN PERSON TO MAKE SURE YOU'VE RETURNED THE SIGNED CONFLICT OF INTEREST FORM, AND THAT WE HAVE ALSO, FOR THOSE WHO WILL BE DEPARTING AT THE END OF THE MEETING, TO GO TO AIRPORTS WE HAVE ARRANGED CABS, AND YOU CAN TALK WITH MISS PHAM, ON MY RIGHT AT THE TABLE. THE OPEN SESSIONS WILL INCLUDE THE DIRECTOR'S REPORT TO COUNCIL, NUMBER OF CONCEPT CLEARANCES, ALSO WE HAVE TO TAKE A VOTE ON THE COUNCIL OPERATING PROCEDURES WHICH WE'LL DO MOMENTARILY. WE WILL BREAK FOR LUNCH AND RECONVENE, WITH A SYMPOSIUM ON THE NIH OVERSIGHT OF CLINICAL TRIALS. COUNCIL MEMBERS RECEIVED A COPY OF THE OCTOBER 2019 MINUTES IN THE ELECTRONIC COUNCIL BOOK. I'D LIKE TO FINALIZE MEETINGS. ARE THERE ANY CORRECTIONS TO THE MEETING MINUTES FOR THE OCTOBER 2019 COUNCIL MEETING? HEARING NONE MAY I HAVE A MOTION FOR APPROVAL OF THOSE MEETING MINUTES? SO MOVED. SECONDED? SECONDED. ANY FURTHER DISCUSSION ON MEETING MINUTES, THE MOTION FOR IT? ALL THOSE IN FAVOR PLEASE RAISE YOUR HAND INDICATING FOR AFFIRMING THE MEETING MINUTES. AND IF ANYONE ON THE PHONE FOR COUNCIL HAS ANY -- IS NOT APPROVING PLEASE INDICATE BY TELLING US NOW. WE'LL ASSUME THE MEETING MINUTES ARE UNANIMOUSLY APPROVED. FUTURE COUNCIL MEETING DATES NOTED ON THE AGENDA, NEXT IN-PERSON MEETING HERE IN BETHESDA ON FRIDAY JUNE 2, 2020, PLEASE BE -- JUNE 5, 2020, LET US KNOW IF YOU WILL NOT BE ABLE TO ATTEND. THE LAST AGENDA ITEM FOR THE OPEN SESSION WILL BE A PUBLIC COMMENT SESSION. IF ANY MEMBERS OF THE PUBLIC ARE HERE AND INTERESTED IN SPEAKING DURING THE PUBLIC COMMENT SESSION, YOU MUST INDICATE YOUR REQUEST BY SIGNING IN ON THE REGISTER SIGN-IN SHEET BY THE ENTRANCE TO THE ROOM. COMMENTS BY THE PUBLIC ARE LIMITED TO FIVE MINUTES EACH AND WILL NOT BE DISCUSSED BY COUNCIL. SO, AS IS REQUIRED BY THE CHARTER FOR THIS COMMITTEE, WE HAVE TO ANNUALLY REVIEW AND THEN COUNCIL HAS TO VOTE TO APPROVE OF ITS COUNCIL OPERATING PROCEDURES. I'M GOING TO QUICKLY TAKE YOU THROUGH THESE. THEY HAVE NOT CHANGED IN SIGNIFICANT FASHION FROM LAST YEAR'S OR THE PRIOR YEARS, FOR THAT MATTER, SO I'M GOING TO RUN THROUGH QUICKLY, IF ANYONE HAS QUESTIONS STOP ME AND WE'LL TAKE A VOTE ON THEM. SO AGAIN THIS IS REQUIRED AS ANNUAL ACTIVITY BY THE CHARTER FOR THIS COUNCIL TO REVIEW AND APPROVE. ESSENTIALLY THE FOLLOWING BULLETED POINTS THAT ARE PART OF THE OPERATING PROCEDURES, THE SECONDARY REVIEW OF GRANT APPLICATIONS THAT WILL BE IN REPORTS TO COUNCIL, THERE WILL BE CONCEPTS TO GET PRESENTED FOR RESEARCH INITIATIVES, ADJUDICATION OF ANY APPEALS THAT ARE SUBMITTED BY GRANT APPLICANTS, AND THEN DISCUSSION OF POLICY AND RESEARCH PRIORITIES. FOR THE REPORTS TO COUNCIL, INFORMS COUNCIL OF SCIENTIFIC BUDGETARY AND/OR LEGISLATIVE ISSUES THAT MAY HAVE IMPACT ON NCCIH OR CHANGE INCLUDING PERSONNEL CHANGES. AS PART OF THE SECONDARY REVIEW OF APPLICATIONS THERE ARE SIX DIFFERENT ASPECTS OF THIS, GRANT APPLICATIONS THAT HAVE NO SPECIAL CONCERNS, THOSE THAT NEED SPECIAL CONSIDERATION, AND THERE ARE VARIOUS OPTIONS AVAILABLE TO COUNCIL. WE ALSO HAVE THINGS RELATED TO ADMINISTRATIVE DECISIONS AND ACTIONS THAT FOLLOW AFTER COUNCIL HAS MET. WE ALSO HAVE A PROCESS FOR EXPEDITED OR EARLY CONCURRENCE AND EXCEPTIONAL SITUATIONS. I'LL GO THROUGH THOSE QUICKLY. FOR APPLICATIONS, GRANT APPLICATIONS WITH NO SPECIAL CONCERNS THEY MAY BE APPROVED EN BLOC, THEY MUST BE RELEVANT TO THE NCCIH MISSION, MUST NOT HAVE CONCERNS REGARDING HUMAN PARTICIPANTS OR ANIMALS OR BIOHAZARDS, CANNOT BE ANY ISSUES IDENTIFIED BY THIS SCIENTIFIC PEER REVIEW REGARDING INCLUSION OF WOMEN, CHILDREN, MINORITY, THESE ALL HAVE TO BE DOMESTIC APPLICATIONS, AND THEY CAN NOT HAVE AN APPEAL FOR THEM. GRANTS THAT NEED SPECIAL CONSIDERATION BY COUNCIL INCLUDING THOSE THAT ARE NOMINATED FOR EITHER HIGH OR LOW PROGRAM PRIORITY, THOSE THAT DO HAVE CONCERNS RELATED TO HUMAN SUBJECTS, ANIMALS OR BIOHAZARDS, THOSE THAT HAVE ISSUES IDENTIFIED BY PEER REVIEW RELATED INCLUSION OF WOMEN, CHILDREN, MINORITIES, IF THEY ARE A FOREIGN APPLICANT OR IT'S BEING APPEALED, AND REVIEW OF APPLICATIONS FROM A GIVEN PRINCIPAL INVESTIGATOR WHO HAS $1 MILLION OR MORE IN DIRECT COSTS TO SUPPORT ON AN ANNUAL BASIS BY NIH. COUNCIL CAN CONCUR, THEY MAY MAKE A RECOMMENDATION OF HIGH OR LOW PROGRAM PRIORITY, THEY CAN DEFER AN APPLICATION TO GAIN ADDITIONAL INFORMATION WHICH WILL BE RECONSIDERED AT THE NEXT MEETING OF COUNCIL, THEY CAN DEFER APPLICATION TO GO BACK FOR RE-REVIEW BY THE INITIAL REVIEW GROUP, COUNCIL MAY RECOMMEND CHANGE IN SCOPE, BUDGET, DURATION, SUPPORT, THOUGH THEY CAN NOT CHANGE PRIORITY SCORE ASSIGNED, AND FINALLY THEY CAN MAKE A RECOMMENDATION OF NOT RECOMMENDED BY COUNCIL. SO THERE'S CERTAIN ADMINISTRATIVE DECISIONS AND ACTIONS THAT FOLLOW COUNCIL. THESE DO NOT REQUIRE ANY RECOMMENDATION BY COUNCIL PER SE. SO AN APPLICATION HAS BEEN DESIGNATED FOR FUNDING. THE APPLICANT, THAT IS THE INSTITUTION, CAN MAKE A -- CAN DECIDE THEY NEED TO OR WANT TO CHANGE THE PRINCIPAL INVESTIGATOR, THE PRINCIPAL INVESTIGATOR MAY DECIDE THEY WANT TO CHANGE THEIR INSTITUTION, APPLICATIONS THAT GET DEFERRED FOR RE-REVIEW AS WELL AS ADMINISTRATIVE SUPPLEMENTS. WE'LL USUALLY INFORM COUNCIL OF THESE SIGNIFICANT CHANGES BUT DO NOT REQUIRE COUNCIL RECOMMENDATION OR VOTE. WE HAVE A PROCESS FOR EXPEDITED OR EARLY CONCURRENCE. THERE ARE A CERTAIN GROUP OF APPLICATIONS THAT MAY BE CONSIDERED FOR EXPEDITED OR EARLY CONCURRENCE, THOSE ARE DOMESTIC WITH NO CONCERNS FOR HUMAN SUBJECTS, ANIMALS OR BIOHAZARDS. WE'LL MAKE A SUBCOMMITTEE OF ONE OR MORE PEOPLE OF COUNCIL ASSIGNED TO REVIEW THIS APPLICATION WHEN THE SUMMARY STATEMENTS BECOME AVAILABLE. FOR SUCH A SUBCOMMITTEE THEY MUST HAVE AT LEAST TWO VOTES IN FAVOR, NO NEGATIVE VOTES TO BE CONSIDERED FOR EXPEDITED CONCURRENCE. AND THEN COUNCIL WILL BE INFORMED OF GRANTS APPROVED BY EXPEDITED CONCURRENCE AT THE NEXT RELEVANT COUNCIL MEETING, THESE ARE ESSENTIALLY NO-BRAINER APPLICATIONS. WE ALSO HAVE EXCEPTIONAL SITUATIONS, WE DO NOT KNOW WHAT THEY ARE BUT IF AN EXCEPTIONAL SITUATION ARISES THE DIRECTOR HAS AUTHORITY TO ACT ON EXTENUATING CIRCUMSTANCES, DIRECTOR MAY CONSULT WITH SUBSET OF COUNCIL MEMBERS TO GET FEEDBACK AND/OR INPUT FROM COUNCIL IN THESE EXCEPTIONAL SITUATIONS, AND ANY ACTIONS TAKEN BY THE DIRECTOR FOR THESE SITUATIONS WILL BE DOCUMENTED AND REPORTED TO COUNCIL. ONE OF THE MAJOR EFFORTS THAT COUNCIL DOES IS REVIEW OF CONCEPTS THAT ARE BEING PRESENTED TO IT FOR RESEARCH INITIATIVES. THESE CONCEPTS CAN COME FROM A VARIETY OF DIFFERENT SOURCES. THEY TYPICALLY COME FROM STAFF BUT THEY CAN ALSO COME FROM THE SCIENTIFIC COMMUNITY ITSELF, CONSTITUENCY ORGANIZATIONS, AND/OR CONGRESS. NCCIH STAFF WILL PREPARE THESE CONCEPT SUMMARIES FOR REVIEW BY COUNCIL IN OPEN SESSION, COUNCIL MAY RECOMMEND APPROVAL, MODIFICATION, DEFERRAL OR DISAPPROVAL OF A GIVEN CONCEPT. APPROVED CONCEPTS MAY THEN LEAD TO ONE OR MORE FUNDING OPPORTUNITY ANNOUNCEMENTS. ALL THIS INFORMATION ABOUT CONCEPTS GETS POSTED ON OUR WEBSITE, IF IT DOES LEAD TO FUND OPPORTUNITY ANNOUNCEMENTS THEY ARE ANNOUNCED IN THE USUAL WAYS. ANOTHER MAJOR ACTION COUNCIL RUNS IS APPEALS BY APPLICANT ORGANIZATIONS WHO ARE APPEALING ESSENTIALLY THE SCORE OR LACK THEREOF FOR A GIVEN APPLICATION. FOR AN APPEAL TO GO FORWARD, THEY HAVE TO HAVE RELEVANT CRITERIA. LISTED ON THE SCREEN ARE COMMON RELEVANT BASES AND NON-RELEVANT. RELEVANT INCLUDE FACTUAL ERRORS THAT MIGHT SIGNIFICANTLY CHANGE PRIORITY SCORE ASSIGNED BY THE PEER REVIEW PANEL. IF THERE'S EVIDENCE OF REVIEWER BIAS, EVIDENCE OF CONFLICT OF HAVE, OR EVIDENCE OF LACK OF SCIENTIFIC EXPERTISE, IT HAS TO BE ONE OR MORE TO BE CONSIDERED FOR APPEAL. THINGS THAT ARE NOT RELEVANT WOULD BE ERRORS OF OMISSION AS SHOWN IN A SUMMARY STATEMENT OR DIFFERENCEES OF SCIENTIFIC OPINION. SO FOR THOSE APPEALS THAT ARE ELIGIBLE, THERE ARE SORT OF ESSENTIALLY TWO THINGS THAT COULD HAPPEN. IF IT'S AN ELIGIBLE APPEAL. IF BOTH PROGRAM STAFF AND REVIEW STAFF AGREE THAT THE APPEAL IS JUSTIFIED, THE GRANT IS AUTOMATICALLY DEFERRED FOR RE-REVIEW BEFORE COUNCIL, ESSENTIALLY GETS THE -- APPLICATION GETS ASSIGNED TO NEXT APPROPRIATE COUNCIL. HOWEVER IF STAFF DISAGREE ABOUT AN APPEAL, THE CENTER'S APPEAL OFFICER ADJUDICATES, AND IF THE APPEAL OFFICER SUPPORTS THE APPEAL THEN IT IS BROUGHT TO COUNCIL FOR YOUR CONSIDERATION. INELIGIBLE APPEALS ARE THOSE NOT BASED ON RELEVANT CRITERIA, APPLICANT'S APPEAL LETTER WILL BE PROVIDED TO COUNCIL MEMBERS THROUGH THE ELECTRONIC COUNCIL BOOK AS AN INFORMATION BUT NOT COME UP FOR VOTE. FORTUNATELY BECAUSE OF CHANGES IN NIH POLICY APPEALS ARE RELATIVELY RARE THESE DAYS. I THINK IT'S BEEN A FEW YEARS IN FACT SINCE THE LAST ONE WE HAVE BROUGHT TO THIS COUNCIL. BUT IT IS ONE OF THE THINGS THAT YOU CAN AND MAY HAVE TO DO. AT THE END OF COUNCIL OPERATING PROCEDURES, I'D LIKE TO ENTERTAIN A MOTION TO APPROVE THESE COUNCIL OPERATING PROCEDURES. SO MOVED. SECONDED? SECONDED. ANY DISCUSSION BY COUNCIL MEMBERS ABOUT THE MOTION OR THE ACTUAL OPERATING PROCEDURES? HEARING NONE, WE'LL GO AHEAD AND TAKE A VOTE OF ALL MEMBERS PRESENT. IF YOU'RE APPROVING FOR THE NEXT YEAR PLEASE INDICATE BY RAISING YOUR HAND. I'LL GET A COUNT. YOU CAN PUT IT DOWN. ANYONE VOTING AGAINST? HEARING NONE, WE'LL MAKE THAT AS UNANIMOUS. >> WELL, GOOD MORNING, AGAIN. IT'S A GREAT PLEASURE TO GIVE YOU THE DIRECTOR'S REPORT. THIS IS -- THIS YEAR HAS BEEN QUITE A MOMENTOUS YEAR FOR US, FOR ME. I HAD MY FIRST ANNIVERSARY HERE AS DIRECTOR, BACK IN NOVEMBER. AND IT'S ALSO BEEN THE 20th ANNIVERSARY AND WE'RE GOING INTO OUR STRATEGIC PLAN. SO, A LOT GOING ON. IT FEELS LIKE A NICE, YOU KNOW, CONVERGENCE. AND IT'S MY -- FIRST, I WANT TO ACKNOWLEDGE OUR TWO AD HOC REVIEWERS IN THE POST SESSION, DR. WILLIAM HELPRICH AND ROBERT SITUICH AND THANK THEM FOR HELPING US REVIEW THE BOTANICAL APPLICATIONS. IT'S MY PLEASURE TO WELCOME OUR NEW EX OFFICIO MEMBER, THE NATIONAL DIRECTOR OF THE INTEGRATIVE HEALTH COORDINATING CENTER, AT THE V.A. HEALTH ADMINISTRATIVE, WHERE HE ALSO SERVES AS DIRECTOR OF WHOLE HEALTH EDUCATION AND RESEARCH IN THE OFFICE OF PATIENT-CENTERED CARE AND CULTURAL TRANSFORMATION HE RECEIVED HIS M.D. FROM BOSTON UNIVERSITY, BOARD CERTIFIED FAMILY PHYSICIAN, WORKING AS CLINICIAN, EDUCATR, RESEARCHER, AND ADMINISTRATIVE LEADER IN THE FIELD OF COMPLEMENTARY AND INTEGRATIVE MEDICINE FOR THE PAST 25 YEARS. HE SERVED IN MANY PROFESSIONAL CAPACITIES, INCLUDING PROFESSOR OF FAMILY AND COMMUNITY MEDICINE AT MOUNT SINAI SCHOOL OF MEDICINE, TEACHING AT THE BETH ISRAEL RESIDENCY PROGRAM IN URBAN FAMILY PRACTICE, AND AS A FACULTY MEMBER OF THE LEADERSHIP PROGRAM IN INTEGRATIVE HEALTH CARE AND DUKE UNIVERSITY. SO WELCOME. WE HAVE HAD SOME STAFF ARRIVALS SINCE OUR LAST COUNCIL. WE HAVE A NEW -- PETER MURRAY IS NEW, PROGRAM OFFICER. JEAN PETTEY, OCRA. CHEREE GRANT, FRONT DESK. KEVIN LIU, NEW TENURE-TRACK INVESTIGATOR IN DIVISION OF PRESIDENT OBAMA RESEARCH. HE IS AT NIDCR, NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH, BUT WE ARE CO-FUNDING HIS APPOINTMENT AND WE'RE VERY EXCITED BECAUSE IT OPENS A LOT OF POSSIBLE COLLABORATIONS, IF WORK IS IN THE AREA OF PAIN. ALSO MOLLY COSGROVE, POSTBAC, AND NICHOLAS MADIAN, ALSO A POSTDOC. WE'VE HAD DEPARTURES, LEEANNE NOCITO LEFT, JOY VANCOOTEN RETIRED, KATIE HOWEES AND LESLIE HERTZ BOTH TOOK OTHER POSITIONS AT NIH. NOW, ONE VERY EXCITING PIECE OF NEWS IS THAT OF OUR NIH-DoD-VA PAIN MANAGEMENT COLLABORATORY GRANTS. ALL OF THE GRANTS, NOW 11, ALL 11 GRANTS HAVE NOW TRANSITIONED TO THE IMPLEMENTATION PHASE. AND THIS IS A TREMENDOUS ACCOMPLISHMENT. THESE ARE -- IT'S A VERY IMPORTANT PROGRAM FOR US, ALL THESE GRANTS HAVE HAD A PRELIMINARY PHASE, ALL MOVING TO RECRUITING SUBJECTS. ANOTHER BIG ITEM IS THE HEAL INITIATIVE, AN EXTENSIVE EFFORT, NCCIH WAS A FULL PARTNER IN THIS. SO THE TWO ASPECTS OF HEAL INITIATIVE, IMPROVING TREATMENT OF OPIOID MISUSE AND ADDICTION AND ALSO PAIN, ENHANCING PAIN MANAGEMENT, WE HAD INITIATIVES IN BOTH OF THESE AREAS. AND THIS WAS TRULY A REMARKABLE INITIATIVE IN SO MANY DIFFERENT WAYS. FIRST OF ALL, BY THE SHEER NUMBER OF RESEARCH PROGRAMS THAT WAS PART OF IT. IT WAS CLEARLY -- IT WAS TRULY A CROSS-NIH EFFORT, 20 INSTITUTES AND CENTERS PARTICIPATED, AND REALLY THE GOVERNMENT STRUCTURE WAS REALLY REFLECTIVE, CROSS-INSTITUTIONAL KIND OF STRUCTURE THAT ALLOWED FOR A LOT OF VERY IMPORTANT COLLABORATIONS. SO, THIS PAST YEAR OVER -- ALMOST A BILLION DOLLARS IN FUNDS, IN GRANTS WERE FUNDED BECAUSE THERE WERE -- FIRST YEAR BECAUSE THE FUNDING WAS SO LATE IN THE FIRST YEAR, IN 2018, A LOT OF THESE FUNDS WERE ESSENTIALLY SPENT IN 2019. BUT THE YEARLY ALLOCATION FOR THE HEAL INITIATIVE IS $500 MILLION A YEAR, AND IT'S GOING TO CONTINUE. SO FAR WE HAVE OVER 40 FUNDING ANNOUNCEMENTS, AND RESULTED IN GRANTS ACROSS 41 STATES, OVER 400 INVESTIGATORS. WE JUST HAD THE FIRST INVESTIGATOR MEETING FOR THE HEAL INITIATIVE, AND IT WAS QUITE REMARKABLE. THE -- YOU KNOW, THE SCOPE OF IT WAS QUITE PALPABLE THERE. AS FAR AS WHAT WE DO AT NCCIH WE WERE LEADING TWO MAJOR INITIATIVES WITHIN "HEAL." ONE IS PRISM INITIATIVE. AND THESE PROGRAMS COMBINED WITH THE GRIM INITIATIVE, I'LL TELL YOU WHAT THEY ARE, COMBINED $87 MILLION OVER SIX YEARS OF FUNDING. PRISM STANDS FOR PRAGMATIC AND IMPLEMENTATION STUDIES FOR MANAGEMENT OF PAIN TO REDUCE OPIOID PRESCRIBING, IT SUPPORTS MULTIPLE PRAGMATIC TRIALS TO CONDUCT RESEARCH EMBEDDED IN HEALTH CARE SYSTEM, WE FUNDED FIVE GRANTS IN THIS PARTICULAR PROGRAM. ONE OF THOSE GRANTS WAS TO INVESTIGATE EFFECT OF ACUPUNCTURE IN OLDER ADULTS WITH LOW BACK PAIN, AN IMPORTANT COLLABORATION WITH THE CMS, CENTER FOR MEDICARE SERVICES, AND THE GRANT, CMS WAS PLANNING ON BASING THEIR COVERAGE DETERMINATION BASED ON THE GRANT -- THE RESULTS OF THE STUDY BUT THEY RECENTLY A COUPLE WEEKS AGO DECIDED TO COVER ACUPUNCTURE. AND SO OUR OWN DOCTOR DEBAR HERE IS ONE OF THE CO-INVESTIGATORS OF THIS STUDY, AND IT'S QUITE REMARKABLE THAT THIS FUNDING DECISION WAS ACTUALLY MADE. THE STUDY REMAINS CRITICALLY IMPORTANT. I MEAN, THE COVERAGE DECISION WAS MADE ASSUMING THAT THE DATA WOULD BE FORTHCOMING. SO BUT THERE'S STILL A LOT OF VERY IMPORTANT INFORMATION THAT WILL BE DERIVED FROM THIS STUDY. WE'RE VERY, VERY EXCITED ABOUT BOTH THE STUDY AND ALSO COVERAGE DECISION ITSELF. THE OTHER NIH HEAL INITIATIVE PROGRAM THAT NCCIH IS LEADING IS BRIM, BEHAVIORAL RESEARCH TO IMPROVE MEDICATION-ASSISTED TREATMENT. WE FUNDED 10 PROJECTS IN THIS INITIATIVE, AND THERE'S ALSO -- THESE ARE ALL PHASED AWARDS THAT WE'LL HAVE DIFFERENT COMPONENTS. THE OTHER NEWS THAT I WANT TO SHARE WITH YOU, SOME CHANGES IN NIH SENIOR LEADERSHIP. FIRST DR. NED SHARPLESS RETURNED AS DIRECTOR OF THE NATIONAL CANCER INSTITUTE AFTER SERVING AS INTERIM FDA ACTING COMMISSIONER. DR. JOSHUA DENNY WAS APPOINTED CHIEF EXECUTIVE OFFICER OF THE "ALL OF US" RESEARCH PROGRAM, DR. DISHMAN REMAINS AS CHIEF INNOVATION OFFICER. DR. MARTHA SOMERMAN RETIRED, AND DR. JOHN NGAI WAS NAMED DIRECTOR OF THE NIH BRAIN INITIATIVE. QUITE A FEW CHANGES IN TEAM LEADERSHIP. OTHER NIH NEWS, WE'RE CONTINUING OUR EFFORTS IN THREE VERY IMPORTANT AREAS AT NIH. ONE IS WORKFORCE DIVERSITY. THE OTHER IS FOREIGN INFLUENCE, AND THE OTHER ONE, THE FINAL ONE, ANTI-HARASSMENT EFFORTS. THESE ARE ONGOING. YOU KNOW, SORT OF EFFORTS THAT WE TAKE VERY, VERY SERIOUSLY, AND WE HAVE EFFORTS THAT ARE BOTH WITHIN NCCIH TO ADDRESS THESE AND ALSO ACROSS NIH. I'M NOW TURNING TO OUR BUDGET. IN YOUR COUNCIL FOLDER YOU WILL FIND THE NCCIH BUDGET TABLES. BUDGET TABLE. AND I WANT TO POINT OUT A FEW THINGS. FIRST OF ALL, WE HAD ANOTHER INCREASE IN OUR BUDGET FOLLOWING -- THIS YEAR. LAST YEAR BUDGET, FY19, WAS 145, 961, AND THIS YEAR OUR BUDGET IS NOW 150, $877 87 -- 150, 877 MILLION. THE OTHER IS THE TOTAL RESEARCH GRANT ALLOCATION FUNDS. AND I WANT TO POINT OUT SOMETHING VERY INTERESTING. THIS WAS FOR FY19, $102 MILLION. I WANT TO CONTRAST THIS AND SHOW YOU THAT THIS $102 MILLION WAS IN OUR FUNDS, WHAT IS IN OUR BUDGET AT NCCIH. BUT IN ADDITION TO THAT WE HAD A SIZEABLE AMOUNT OF MONEY THAT CAME FROM THE SPECIAL INITIATIVES, INCLUDING THE HEAL INITIATIVE THAT I JUST TALKED ABOUT, $43 MILLION, AND THEN ALSO A LOT OF CO-FUNDING FROM OTHER I.C.s. I'M GOING TO TALK ABOUT THESE, OTHER INSTITUTES AND CENTERS THAT CO-FUND GRANTS. AND WE PARTNER WITH A LOT OF OTHER INSTITUTES IN TRYING TO LEVERAGE OUR BUDGET AND REALLY KIND OF EXPAND OUR ABILITY TO FUND. SO THE TOTAL OF THESE TWO ADDITIONAL BUCKETS ADDS ANOTHER $62 MILLION IN ADDITIONAL FUNDS, SO IT'S MORE THAN HALF OF THIS $102 MILLION. I WANT TO GIVE YOU A SENSE OF THE SCOPE OF WHAT WE'RE ABLE TO DO BY HARNESSING THE VARIOUS DIFFERENT OTHER TYPES OF SOURCES OF FUNDING. THIS IS JUST TO GIVE A BREAKDOWN OF, FOR EXAMPLE, IN "HEAL," SO THE TWO PROGRAMS THAT I MENTIONED, PRISM AND BRIM, AND AN ADDITIONAL AMOUNT OF FUNDING HERE FOR OPIOID, YOU KNOW, INITIATIVES AS WELL. IN THE PAIN MANAGEMENT COLLABORATORY, THIS IS THE DoD/VA COLLABORATORY I TALKED ABOUT, THERE'S FUNDING FROM THE DoD, FROM THE V.A., ALSO FROM OTHER INSTITUTES AND CENTERS AT NIH. EVERYTHING THAT'S IN BLUE HERE IS WHAT WE FUND, OKAY? YOU CAN SEE THAT, YOU KNOW, THERE'S A LOT OF OTHER THINGS THAT SUPPLEMENT THAT. HEALTH CARE RESEARCH SYSTEMS COLLABORATORY IS ANOTHER AREA WHERE WE GET A LOT OF CO-FUNDING FROM OTHER INSTITUTES AS WELL AS FROM THE COMMON FUND. AND FINALLY THE MUSIC IN HEALTH PROGRAM HAS SOME SUBSTANTIAL AMOUNTS OF CO-FUNDING FROM OF CO-FUNDING FROM INSTITUTES AND CENTERS. WE'RE CAUTIOUSLY OPTIMISTIC, BIPARTISAN SUPPORT TO MAKE IT EASIER TO CONDUCT RESEARCH ON CANNABIS PRODUCTS THAT PEOPLE ARE USING INSTEAD OF HAVING TO USE VERY RESTRICTED SOURCES ADMINISTERED BY NIDA, THERE'S ONLY ONE FARM SOURCE AVAILABLE FOR CANNABIS. WE DON'T HAVE ANY FURTHER UPDATES ABOUT THIS, BUT THIS IS IMPORTANT TO FOLLOW, AS THIS DEVELOPS. WE FUNDED 11 GRANTS ON MINOR CANNABINOIDS AND TURPENES, WITH MORE OPPORTUNITIES GOING FORWARD. NOW RESEARCH HIGHLIGHTS, I'M GOING TO HIGHLIGHT PAPERS THIS FROM DR. CARRASQUILLO, ONE OF OUR INTRAMURAL TENURE TRACK INVESTIGATORS, A NICE PAPER THAT CAME OUT RECENTLY ON ROLE OF CENTRAL AMYGDALA. THEY FOUND IT FUNCTIONS AS SORT OF WHAT THEY CALL A RHEOSTAT, THERE'S TWO POPULATIONS OF CELLS, ONE OF PKC DELTA, THE OTHER SOMATOSTATIN. DEPENDING ON WHICH OF THE NEURONS POPULATIONS IS ACTIVATED IT CAN DAMPEN PAIN OR ENHANCE IT. THIS IS ALL WITHIN THE CENTRAL AMYGDALA, VERY INTERESTING. THIS OTHER PAPER ILLUSTRATES ONE OF OUR CO-FUNDING, THIS IS A GRANT THAT IS FUNDED BY NIDDK, THAT WE ALSO CO-FUND FROM NCCIH. THIS IS A PAPER IN "CELL" FROM A MULTI-CENTERED TEAM OF SCIENTISTS LED BY RESEARCHERS AT HARVARD MEDICAL SCHOOL THAT FOUND THAT THERE ARE CGRP POSITIVE NOCICEPTORS THAT ACTIVATE CELLS IN THE GUT THAT PLAY A ROLE IN TRANSPORTING BACTERIAL ANTIGENS TO THE LAMINAPROPRIA, THERE WAS INTERACTION BETWEEN NERVOUS SYSTEM AND NOCICEPTORS AND ALSO THE IMMUNE FUNCTION OF THE GUT ABLE TO DEFEND AGAINST PATHOGENS IN THE GUT, HELPED THE GUT DEAL WITH PATHOGENS SUCH AS SALMONELLA. NOW, THIS PARTICULAR OTHER STUDY, ANOTHER ILLUSTRATION OF PARTNERSHIPS, THIS ONE WITH NIAMS, NATIOAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL DISEASES. AND SKIN DISEASES. THIS IS A STUDY IN RATS THAT FOUND DIETARY SUPPLEMENTS WITH MIXTURE OF SEVERAL PLANT-DERIVED POLYPHENOLS REDUCE THE PAIN ASSOCIATED WITH INTERVERTEBRAL DISK DEGENERATION. ALL THESE STUDIES, BY THE WAY, ARE IN YOUR PACKET. THIS STUDY WE WANT TO SHOW YOU, IT'S AN INTERESTING APPROACH, AN NCCIH STUDY, AND THIS IS A STUDY THAT LOOKS AT ACCESS TO CHIROPRACTIC CARE AND IT WAS RECENTLY PUBLISHED IN THE AMERICAN JOURNAL OF MANAGE THE CARE, AND RESEARCHERS FROM VARIOUS ARMS OF THE UNIVERSITY OF MICHIGAN AND RICE UNIVERSITY LOOKED AT THE ACCESSIBILITY TO CHIROPRACTIC CARE IN PATIENTS WHO MOVED FROM ONE LOCATION TO ANOTHER, AND FOUND WHETHER THEY MOVED FROM AN AREA THAT HAD OR MORE OR LESS ACCESS TO CHIROPRACTIC CARE, AND THEY LOOKED AT HEALTH CARE EXPENDITURES, DEPENDING ON WHETHER PEOPLE HAD MORE VERSUS LESS ASPECT, AND THERE WAS A SUGGESTION MOVING TO AN AREA WITH MORE ACCESS TO CHIROPRACTIC CARE REDUCED SOME HEALTH CARE COSTS, RELATED TO PAIN AND IMAGING AND THIS KIND OF THING. I ALSO WANT TO HIGHLIGHT A PAPER THAT IS CO-AUTHORED BY DR. NAHIN AND STUSSMAN AND BARNES, VERY INTERESTING OBSERVATIONS, EPIDEMIOLOGICAL STUDIES ON USAGE OF COMPLEMENTARY AND INTEGRATIVE PRACTICES. THIS ONE IS ABOUT RECOMMENDATIONS, HOW MANY -- WHAT IS THE PERSONAL OF PHYSICIANS THAT ACTUALLY RECOMMEND COMPLEMENTARY HEALTH APPROACHES, AND SO THIS IS -- THEY FOUND THAT FEMALE PHYSICIANS APPARENTLY RECOMMENDED COMPLEMENTARY HEALTH APPROACHES AT A HIGHER RATE THAN MALE PHYSICIANS YOU ABOUT OVERALL MORE THAN -- OVER 50% OF PHYSICIANS ACROSS THE BOARD RECOMMENDED COMPLEMENTARY HEALTH APPROACHES IN THE -- DURING AN OFFICE VISIT. THIS NEXT -- LAST PAPER IS A VERY, VERY COOL PAPER THAT WAS PUBLISHED BY SOME OF OUR COMMUNICATIONS, OUR DIRECTOR OF COMMUNICATION, KATHERINE LAW AND KATY DANIELSON, A PAPER ABOUT TWITTER, CONVERSATIONS THAT OCCUR ON TWITTER. AND HOW PAIN PATIENTS AND HEALTH CARE PROVIDERS DIFFER. SO I'LL JUST SHOW YOU A COUPLE ILLUSTRATIONS HERE, LOOK AT THE ONE ON THE LEFT, THIS IS THE PAIN FIELD. SO YOU SEE CHRONIC PAIN PATIENTS, THIS IS KIND OF HOW THEY CLUSTER WHEN YOU LOOK AT WHAT THEY CALL THE NODES OF -- WHAT THEY CALL ATTENTIVE CLUSTERING, HOW THEY TEND TO CHAT TOGETHER. YOU SEE THE PROVIDERS ARE OUT HERE, COMPLETELY SEPARATE. AND THEN OUT HERE IN THE CORNER HERE THIS LIGHT GREEN ARE NON-PHARMACOLOGICAL PAIN TREATMENT CHATS. YOU CAN SEE THEY ARE ALSO IN AN ISLAND OF THEIR OWN. BUT WHEN YOU LOOK AT ONCOLOGY, PRACTICE, YOU KNOW, CONVERSATIONS ABOUT ONCOLOGY, WHETHER THEY ARE PATIENT, HEALTH CARE PROVIDER, YOU CAN SEE IT'S MUCH MORE MIXED. THIS IS AN INTERESTING OBSERVATION THAT THE TWITTER FIELD SEEMS TO BE QUITE POLARIZED, PROBABLY COULD USE MORE INTEGRATION. I'M GOING TO TALK ABOUT SOME FUNDING INITIATIVES NOW. A FEW FUNDING OPPORTUNITIES. SO THIS IS A FUNDING OPPORTUNITY WITHIN THE HEAL INITIATIVE. AND THIS IS A REISSUE OF THE PRISM, TO REDUCE OPIOID PRESCRIBING, AND THE IMPORTANT DATE HERE IS THAT THERE'S A TECHNICAL ASSISTANT VIDEOCAST SCHEDULED FOR MARCH 2, SO IF WE'LL WANT INFORMATION ABOUT THAT, THAT'S A GOOD PLACE TO DO IT. ANOTHER FUNDING OPPORTUNITY IS THE EMOTIONAL WELL-BEING, HIGH PRIORITY RESEARCH NETWORKS. THIS IS AT A U24 GRANT, WHICH WILL FACILITATE RESEARCH NETWORKS THROUGH MEETINGS, CONFERENCES, SMALL SCALE PILOT RESEARCH, MULTI-DISCIPLINARY CROSS-TRAINING SUCH AS WORKSHOPS, ET CETERA. SO, AGAIN, THERE'S A TECHNICAL ASSISTANCE VIDEOCAST SCHEDULED FOR MARCH 17 ABOUT THIS PARTICULAR INITIATIVE AND FUNDING OPPORTUNITY. THIS IS A NOTICE OF SPECIAL INTEREST. SO WE CALL THEM NOSIs. WHEN WE POST A NOSI, THAT MEANS WE'RE POINTING, WE'RE ALERTING THE COMMUNITY TO A FUNDING OPPORTUNITY AND POINT THEM TO AN ALREADY EXISTING OR DIFFERENT SORT OF REQUEST FOR APPLICATION. AND THIS PARTICULAR ONE IS ABOUT THE MECHANISMS UNDERLYING ANALGESIC PRODUCTS OF MINOR CANNABINOIDS AND TERPENES IS AND WHERE TO GO TO FIND THAT. I BELIEVE IN THIS CASE IT'S THE PARENT -- IT'S NOT AN RFA, IT'S USING THE PARENT FUNDING OPPORTUNITY. ANYWAY, THE NOSI EXPLAINS THAT. ANOTHER FUNDING OPPORTUNITY IS THIS -- ANOTHER NOSI IS FOR THIS ONE ON SPECIAL INTERESTS, ALZHEIMER'S-FOCUSED ADMINISTRATIVE SUPPLEMENT FOR NIH GRANTS THAT ARE NOT FOCUSED ON ALZHEIMER'S DISEASE. IT MEANS IT'S JUST TO SUPPLEMENT A GRANT AND ADD SOMETHING THAT COULD MAKE IT RELEVANT TO ALZHEIMER'S. ACTIVE AWARDS FOR THIS PROJECT END DATES ARE IN FY 21 OR LATER ARE ELIGIBLE. SO, SOME WORKSHOPS AND PAST EVENTS, SO THIS WAS OUR 20th ANNIVERSARY CELEBRATION, WHICH WAS REALLY A WONDERFUL DAY. I BELIEVE THAT WE HAVE THE VIDEOCAST AVAILABLE THAT YOU CAN WATCH THEM IF YOU'RE INTERESTED. WE HAD SOME WONDERFUL SPEAKERS. IT WAS JUST A REALLY FUN DAY ALL AROUND. THE-- WE ALSO HAD A VERY SUCCESSFUL WORKSHOP ON CONCEPTS OF IMPLEMENTATION AND DEIMPLEMENTATION. THIS WAS A WORKSHOP, THE CHARGE OF THE GROUP WAS TO FOCUS ON DISCUSSIONS OF IMPLEMENTING OR DEIMPLEMENTING COMPLEMENTARY AND INTEGRATE APPROACHES, WHAT ARE READY, AND MOVING INTO THE HEALTH CARE SYSTEM. UPCOMING EVENTS, WE'RE GOING TO NOW REALLY START RAMPING UP OUR STRATEGIC PLANNING ACTIVITIES, AND THE FIRST ONE IS GOING TO BE A STRATEGIC PLANNING WEBINAR. AND I HOPE YOU CAN ALL JOIN US. THIS IS GOING TO BE ON -- WHAT'S THE DATE ON THIS? FEBRUARY 19. IT SHOULD HAVE BEEN BEEN IN BIGGER LETTERS, SORRY. AND SO AT THIS WEBINAR WE'RE GOING TO BE REALLY KIND OF INTRODUCING SOME OF THE CONCEPTS OF WHOLE PERSON HEALTH THAT WE ALREADY DISCUSSED AT COUNCIL, AT THE LAST COUNCIL, AND THIS IS REALLY KIND OF TO EXPAND THAT AND GET INPUT FROM THE COMMUNITY ABOUT THIS. OUR INTEGRATIVE MEDICINE LECTURE SERIES IS KICKING OFF AGAIN IN THE SPRING. WE'RE GOING TO HAVE OUR LECTURES ON MINDFULNESS-ORIENTED RECOVERY ENHANCEMENT, A TECHNIQUE CALLED "MORE," THIS IS FOR REDUCING CRAVINGS FOLLOWING TREATMENT FOR OPIOID ADDICTION, DR. ERIC GARLAND. DR. ALICIA HEAPY WILL BE GIVING A TALK ON COOPERATIVE PAIN EDUCATION AND SELF-MANAGEMENT FOR PAIN. AND DR. HELEN BURGESS IS GOING TO TALK ABOUT LIGHTING UP OUR LIVES, HOW LIGHT CAN INFLUENCE OUR MENTAL AND PHYSICAL HEALTH. THE GENERAL THEME OF THE LECTURES IS KIND OF PAIN AND SORT OF ADDICTION, IT'S VERY MUCH IN THE SPIRIT OF THE HEAL INITIATIVE. THE INTERNATIONAL CONGRESS ON INTEGRATIVE MEDICINE AND HEALTH, ICIMH, NCCIH WILL HAVE A HUGE PRESENCE. I'LL GIVE YOU A DAY TO DAYBREAK DOWN OF WORKSHOPS AND SYMPOSIUM STARTING FROM THE FIRST DAY, I DON'T KNOW IF IT'S TUESDAY OR WEDNESDAY, 28th OF APRIL, SO WE'RE GOING TO HAVE A WORKSHOP ON TRANSLATING RESEARCH FOR PUBLIC CONSUMPTION, IT'S REALLY ABOUT COMMUNICATING ABOUT RESEARCH. WE'LL HAVE ANOTHER WORKSHOP ON -- A SESSION ON CAREER DEVELOPMENT. THE FOLLOWING DAY, APRIL 29, IS CHOCK FULL. I'M GOING TO GIVE A PLENARY ON WHOLE PERSON HEALTH AND STRATEGIC VISION FOR NCCIH. WE'LL HAVE ANOTHER SESSION ON COMPLEMENTARY AND INTEGRATIVE HEALTH APPROACHES IN HEALTH CARE SYSTEMS, CLINICAL TRIALS DESIGN, PAIN AND INFLAMMATION AND SLEEP. SO MANY, MANY DIFFERENT SESSIONS. THE FOLLOWING DAY WE'RE GOING TO HAVE A BEHAVIORAL APPROACH FOR OPIOID USE DISORDER, CHRONIC PAIN MANAGEMENT, VIRTUE REALITY AND A SESSION ON GLIM -- GLYMPHATICS, AND A TOWN HALL, WE'RE HOPING FOR A FULL HOUSE AND GREAT INPUT ON THE STRATEGIC PLAN. AND FINALLY ON MAY 1 WE'LL HAVE A SESSION ON CANNABINOIDS, ONE ON mHEALTH, ONE ON THE BRAIN INITIATIVE. SO IT'S GOING TO BE VERY, VERY BUSY. WE ALSO ARE PLANNING A MYOFASCIAL PAIN WORKSHOP IN THE CONTEXT THAT'S FUNDED BY THE HEAL INITIATIVE, AND THIS IS PLANNED FOR LATE SUMMER AND EARLY FALL. THIS IS GOING TO BE TO LOOK AT MYOFASCIAL PAIN, WHICH IS REALLY AN AREA THAT HAS A REAL GAP I THINK IN THE LITERATURE ON OUR UNDERSTANDING, WHAT CAUSES IT, HOW TO TREAT IT. STAY TUNED FOR THAT. AND OUR NEXT MEETING IS GOING TO BE JUNE 5. THAT'S ALL FOR ME. HOW DID WE DO? WE HAVE A COUPLE MINUTES. ANY COMMENTS OR QUESTIONS? NO COMMENTS? WE MADE UP SOME TIME. ALL RIGHT. THANK YOU. >> ALL RIGHT. SO WE WILL NEXT MOVE TO A SERIES OF CONCEPT CLEARANCES THAT WILL BE PRESENTED BY STAFF TO COUNCIL, OPPORTUNITIES FOR DISCUSSION AND THEN WE'LL TAKE A VOTE ON EACH CONCEPT CLEARANCE AS IT -- AT THE END OF EACH ONE. THE FIRST IS A CONCEPT CLEARANCE PRESENTED BY A TAG TEAM I BELIEVE IS THE WAY WE'RE TALKING ABOUT THIS, DOCTORS MUDD, SABRI AND ELWOOD. THIS IS INTEGRATING BASIC BEHAVIORAL AND SOCIAL SCIENCE TRAINING FOR MID-CAREER INVESTIGATORS. >> WE HAVE TO LOAD SLIDES. >> NOW WE GET TO FILL THE SPACE. [LAUGHTER] ANYONE KNOW A GOOD JOKE? >> I CAN USE THIS MOMENT TO LET YOU KNOW -- (INAUDIBLE) -- >> WHY WOULD YOU BE WANTING TO DO THIS, KATHERINE? CAN YOU SPEAK INTO THE MICROPHONE? >> OKAY. IT'S THE HEART TRUTH CAMPAIGN, AMERICAN HEART ASSOCIATION, NATIONAL HEART, LUNG AND BLOOD INSTITUTE CELEBRATING RED WEAR DAY, RECOGNIZING IMPORTANCE OF CARDIOVASCULAR HEALTH, A SOCIAL MEDIA CAMPAIGN TODAY AND FEBRUARY 7 IS WEAR RED DAY. >> HENCE YOU'LL NOTICE A NUMBER OF STAFF ARE WEARING RED. THAT'S WHY. >> ALL RIGHT, GREAT. GOOD MORNING, EVERYONE. I'M LANAY MUDD, PROGRAM OFFICER AND TRAINING OFFICER FOR NCCIH. I'M JOINED TODAY BY MY COLLEAGUE DR. BILL ELWOOD FROM BEHAVIORAL AND SOCIAL SCIENCE RESEARCH TO DISCUSS A CONCEPT CLEARANCE FOR MID-CAREER ENHANCEMENT AWARD TO INTEGRATE SOCIAL SCIENCES. THIS CONCEPT IS ACTUALLY -- OKAY. THERE WE GO. ALL RIGHT. THIS CONCEPT IS ACTUALLY BEING LED BY OBSSR'S BASIC BEHAVIORAL AND SOCIAL SCIENCE OPPORTUNITY NETWORK, AND THEY ARE COMING HERE TO OUR COUNCIL FOR COUNCIL CLEARANCE FOR THIS INITIATIVE. AND SO WE'RE GOING TO PROVIDE AN OVERVIEW OF THE COLLABORATION BETWEEN NCCIH AND OppNet AND MOCH INTO -- MOVE INTO THE PURPOSE OF THE TRANS-NIH INITIATIVE WITH SUPPORT FROM SEVERAL DIFFERENT I.C.s, SO FAR, WHICH YOU CAN SEE LISTED ON THE SCREEN AND WE WILL BE SEEKING SUPPORT FROM OTHER INSTITUTES AND CENTERS ACROSS NIH AS WELL IF THIS MOVES FORWARD. >> THANKS, LANAY. NIAAA JUST EXPRESSED INTEREST IN JOINING THIS INITIATIVE. LANAC TOLD YOU OppNet IS OUR SHORT HAND TERM FOR INITIATIVE THAT'S BEEN AROUND FOR A DECADE NOW. A TRANS-NIH COLLABORATION THAT TRIES TO FOSTER RESEARCH ABOUT THE UNDERLYING MECHANISMS AND PROCESSES THAT INFORMS HEALTH BEHAVIORS BUT RESEARCH THAT DOESN'T FIT NEATLY WITHIN THE BAILIWICK OF ANY INDIVIDUAL OR CENTER'S MISSION. WE COMPLEMENT AND ENHANCE RATHER THAN REPRODUCE. ORIGINALLY PLANNED AS A FIVE-YEAR INITIATIVE, OppNet BROUGHT IN A TREMENDOUS NUMBER OF ESIs, AND FUNDED GRANTS TO BASIC BEHAVIORAL RESEARCH GRANTS, APPROXIMATELY 40 OF WHICH DID NOT RECEIVE THE RCDC FINGERPRINT FOR bBSSR. THUS EXPANDING THE PORTFOLIO AND LEADING US TO CHANGE OUR BOOTPRINT DEFINITION. BECAUSE OF THESE AND OTHER SUCCESSES NIH LEADERS DECIDED WE SHOULD MAINTAIN OppNet AS A VOLUNTARY INTELLECTUAL SCIENTIFIC COLLABORATIVE IN WHICH ALL ICOS PARTICIPATE INTELLECTUALLY, AND THEN INDIVIDUAL INSTITUTES WHO WANT TO PARTICIPATE IN A FOA DO SO, REGARDLESS OF WHO PARTICIPATES IN THE -- WHICH I. PARTICIPATES IN THE FOA, OBSSR PROMPTLY DELIVERS CO-FUNDING FOR ALL YEARS OF THE PROJECTS THAT INDIVIDUAL INSTITUTES AND CENTERS DECIDE THEY WANT TO INVEST AND MANAGE. I'M STILL UP? SORRY. >> SO I THINK WE WANTED TO TALK ABOUT HOW THIS INITIATIVE THAT WE'RE PROPOSING WILL ALLOW US TO CONTINUE SUPPORT FOR MID-CAREER ENHANCEMENT, AND WE HAVE A COUPLE EXAMPLES OF PREVIOUS SUCCESSES. >> THANK YOU SO MUCH. OUR FIRST EXAMPLE IS DR. KATHY LUSTYK, YOU CAN SEE HERE THOUGH THIS WAS NOT AN NCCIH-MANAGED PROJECT, BECAUSE HER WORK WAS LOOKING AT ADDICTION, IT WAS FOR NIDA, YOU CAN SEE HOW VERY NICELY IT FITS INTO NCCIH'S INTERESTS. WHAT YOU HAVE HERE IS THE TITLE OF THE PROJECT, TWO ARTICLES THAT CAME AS THE RESULT OF THIS PROJECT, AND HER CAREER TRAJECTORY. IF YOU HAVE ACCESS TO THESE SLIDES, ALL OF THESE ARE HYPERLINKS, SO YOU CAN ACCESS THE PROJECT AND REPORTER, READ THE ARTICLES. DR. LUSTYK'S TEAM HELPED HER EXPAND AND GROW THE WOMEN'S HEALTH LAB AT SEATTLE PACIFIC UNIVERSITY, AND THOUGH SHE DID INSTEAD SHE WAS LURED AWAY TO HELP DEVELOP THE RESEARCH TRAJECTORY AT PRESCOTT CAMPUS OF EMBRY-RIDDLE UNIVERSITY. OUR SECOND EXAMPLE IS KAREN WESTLUND-HIGH, A MEMBER UNTIL SHE SAW THE -- UNTIL SHE APPLIED TO THE K18, EXCUSE ME, SPENT MUCH OF HER TIME IN PANCREATIC CANCER PAIN AND DENTAL CRANIOFACIAL PAIN. SO IN THIS EXAMPLE SHE RECEIVED TRAINING IN BRAIN IMAGERY, AND ADDICTION, THUS AGAIN RELATING VERY CLOSELY TO THIS MISSION, TO YOUR MISSION, ALTHOUGH GIVEN HER HISTORY WITH NIDCR THAT WAS THE INSTITUTE THAT MANAGED THIS PROJECT. YOU CAN SEE HER TRAJECTORY BASED ON THIS ONE-YEAR OF A PROJECT THAT BOUGHT OUT SOME OF HER TIME, AND ALLOWED HER A MENTORED RESEARCH PROJECT IN WHICH SHE GAINED EXPERIENCE PUBLISHING THREE ARTICLES, THREE SUBSEQUENT RESEARCH GRANTS, THE COMPETITIVE RENEWAL INCLUDED IN ARM BASED ON HER K18 PROJECT, AND YOU ALSO CAN SEE HER CAREER ADVANCEMENT AS WELL. >> GREAT. WE HAVE ONE FINAL EXAMPLE, THAT'S ACTUALLY AN ONGOING PROJECT FOR DR. ROIN PUETT. THIS IS ANOTHER EXAMPLE OF A MID-CAREER ENHANCEMENT AWARD, HER BACKGROUND WAS IN ENVIRNMENTAL EPIDEMIOLOGY. SHE WAS STUDYING ENVIRONMENTAL ASPECTS OF ASTHMA. AND SHE REALLY BECAME INTERESTED IN HOW MINDFULNESS INTERVENTIONS MIGHT HELP WITH ANXIETY RELATED TO ASTHMA ATTACKS. SO HER PROPOSAL SHE PROPOSED TO WORK WITH DR. RICHIE DAVIDSON AND HIS LAB TO UNDERSTAND MINDFULNESS RESEARCH BETTER, AND TO GAIN TRAINING IN NEURAL BIOLOGY AND PHYSIOLOGY OF MINDFULNESS, AND THEY ARE CONDUCTING SECONDARY ANALYSES TO IDENTIFY OVERLAPS BETWEEN MINDFULNESS AND ENVIRONMENTAL EXPOSURES. AND CONDUCT SOME FORMATIVE WORK TO DEVELOP AN ENVIRONMENTALLY INFORMED MINDFULNESS INTERVENTION FOR ASTHMA SYMPTOMS. WITH THESE PROJECTS IT'S NOT ONLY ABOUT ADDING NEW KNOWLEDGE FOR THESE MID-CAREER INDIVIDUALS, IT'S ALSO ABOUT FORMING SOME INTERDISCIPLINARY COLLABORATIONS THAT CAN MOVE FORWARD TOGETHER INTO NEW RESEARCH PROJECTS. AND SO THE PURPOSE OF THIS PROPOSED INITIATIVE IS TO HELP US CONTINUE TO PROVIDE OPPORTUNITIES FOR MENTORED RESEARCH TRAINING, FOR INVESTIGATORS WHO WANT TO EXPAND BEYOND THEIR CURRENT RESEARCH PROJECTS, AND ACQUIRE NEW SKILLS AND KNOWLEDGE, AND DIFFERENT AREAS RELATED TO BASIC BEHAVIORAL AND SOCIAL SCIENCE RESEARCH. AND SO APPLICATIONS COULD PROPOSE TRAINING AND COLLABORATIONS ACROSS A BROAD RANGE OF TOPICS, WHICH YOU CAN SEE LISTED HERE, AND REALLY THE OBJECTIVES OF THIS TYPE OF INITIATIVE ARE GOING TO FOCUS ON CROSS-TRAINING, AND HELPING INVESTIGATORS GAIN THESE NEW SKILLS AND ESTABLISH NEW RESEARCH TEAMS TO TAKE THEM IN NEW DIRECTIONS AND ADD NEW DIRECTIONS. WE'RE HAPPY TO TAKE QUESTIONS. I'LL TAKE NO QUESTIONS AS MEANING YOU'RE REALLY EXCITED ABOUT THIS. >> OKAY. SO IF I CAN ENTERTAIN A MOTION FOR APPROVAL BY COUNCIL OF THIS PARTICULAR CONCEPT, SO SECONDED. ANY DISCUSSION BY COUNCIL ON THE MOTION OR ANY CONTENT OF THIS? I'LL ASK FOR A VOTE, FOR THOSE VOTING TO APPROVE THIS CONCEPT PLEASE INDICATE BY RAISING YOUR HAND HIGH AND HOLD IT UP SO WE'LL GET A COUNT. ANYONE VOTING IN OPPOSITION? OKAY. OH, THAT'S RIGHT, WE ALSO HAVE -- FOR THOSE ON THE VIDEO CONFERENCE, I WANT TO ASK YOU, SO HOPEFULLY YOU'RE STILL THERE. DR. SONNEN BERG? DO WE STILL HAVE DR. SONNEN BERG? DR. HENSEL? >> I'M HERE, I APPROVE. >> DR. TIMER MAN? >> I APPROVE. >> DR. YAY? >> I APPROVE. >> THANK YOU. 174, NONE AGAINST. GREAT, THANK YOU. WE'LL MOVE TO THE NEXT CONCEPT CLEARANCE, PRESENTED BY DR. SABRI AND CHEN, IMAGING OF MYOFASCIAL TISSUE. >> GOOD MORNING, I'M WEN CHEN, CHIEF FOR THE BASIC MECHANISTIC BRANCH. I HAVE TWO ACTS TO CONSIDER, FIRST IS RESEARCH CONCEPT, RESEARCH INITIATIVE CONCEPT RELATED TO THE NIH HELPING TO END ADDICTION LONG TERM, ALSO KNOWN AS HEAL INITIATIVE. THE TITLE OF THIS CONCEPT IS QUANTITATE I CAN EVALUATION, IMPLICATION IN MUSCULOSKELETAL PAIN RESEARCH. WE KNOW MUSCULOSKELETAL PAIN IS IN PARTICULAR CHRONIC LOW BACK PAIN AND CHRONIC SHOULDER PAIN IS ONE OF THE MAJOR DRIVING FORCES FOR CHRONIC PAIN PATIENTS TO SEEK FOR LONG-TERM USAGE OF OPIOID-BASED PAIN MEDICATIONS. IT HAS BEEN ESTIMATED THAT OH, ADVANCE, THANK YOU. IT'S BEEN ESTIMATED APPROXIMATELY 30 TO 85% OF MUSCULOSKELETAL PAIN PATIENTS HAVE PAIN ORIGINATED FROM MUSCLES, OR SOFT TISSUE SUCH AS FASCIA, AND IT'S A CONDITION CALLED MYOFASCIAL PAIN SYNDROME. THIS PAIN SYNDROME IS CURRENTLY DIAGNOSED PRIMARILY BY CLINICAL HEALTH PATIENTS OF THE HARD NODULES IN THE MUSCLES AND THE SOFT TISSUES, CONNECTIVE TISSUES, CALLED THE MYOFASCIAL TRIGGER POINTS. AS WELL AS LOCAL PAIN OR THE RADIATING PAIN TO OTHER PARTS OF THE BODY. LIKE MOST OF THE MUSCULOSKELETAL PAIN CONDITIONS, SOME OF THE PATIENTS WITH MYOFASCIAL PAIN SYNDROME, THE STANDARD PAIN THERAPIES DO NOT WORK FOR THEM. AND THEY LOOK FOR OPIOID-BASED PAIN MEDICATIONS, WHICH REALLY LEADS TO THE POSSIBILITY FOR THEM TO GET INTO LONG-TERM OPIOID USAGE AND ADDICTION. SO IN THE FIELD OF MUSCULOSKELETAL PAIN RESEARCH CURRENTLY A SUBSTANTIAL RESEARCH AND TREATMENT INVESTMENT AND EFFORTS HAVE BEEN FOCUSED ON THE SKELETAL SYSTEM SUCH AS BONES, JOINTS, AND INTERVERTEBRAL REALLY INTERVENTIONS SUCH AS SURGERY IN EFFORT TO CORRECT THOSE SKELETAL ABNORMALITIES OR CENTRAL NERVOUS SYSTEM, OPIOID-BASED MEDICATIONS TO NUMB THE PAIN SENSATION. MANY PATIENTS WITH MUSCULOSKELETAL PAIN DO NOT RESPOND TO SURGERY OR DEVELOP SIGNIFICANT SIDE EFFECTS TO OPIATE THERAPIES, OR BOTH. IN CONTRAST, VERY LITTLE IS KNOWN ABOUT WHAT HAPPENS TO THE DAMAGES AND THE INJURIES TO THE MUSCLES AND THE CONNECTIVE TISSUES WHICH ARE MANY TIMES PART OF THE CAUSES OF THOSE PAIN OR THE CO-CONTRIBUTORS TO THE MUSCULOSKELETAL PAIN. THOSE DAMAGES AND INJURIES HAVE REMAINED LARGELY UNDERSTUDIED. CURRENTLY THERE ARE VERY FEW QUANTITATIVE EVALUATIONS OF THE PATHOLOGY INCLUDING MYOFASCIAL TISSUES. AND THOSE TISSUES REMAIN LARGELY AS UNTURNED STONE IN THE MUSCULOSKELETAL PAIN RESEARCH. SO THIS PROPOSAL, THIS PROPOSED HEAL INITIATIVE HERE WOULD LIKE TO BRING RESEARCH SPOTLIGHT TO THE MYOFASCIAL -- TO THE UNDERSTUDIED MYOFASCIAL TISSUES IN MUSCULOSKELETAL PAIN RESEARCH. THIS DIAGRAM ACTUALLY ALONG WITH ULTRASOUND IMAGES HERE REALLY ILLUSTRATES, I'LL GIVE EXAMPLE OF THE STRUCTURES AND COMPONENTS OF THE TISSUES INVOLVED, AS WELL AS COMPLEXITY OF THE SITUATION. YOU CAN SEE IN THE FIGURE, THIS IS A HUMAN THORACOLUMBAR FASCIA, YOU CAN SEE MULTIPLE LAYERS IN THIS TISSUE, AS ILLUSTRATED BY THOSE COLORED PLANES HERE, THE PURPLE, THE YELLOW, GREEN, AND THE BLUE. EACH OF THE LAYERS ARE REALLY CONNECTED TO DISTINCT GROUPS OF MUSCLE. WHEN THE TISSUES ARE STRETCHED OR COMPRESSED OR PULLED AND PUSHED, THEY CAN ACTUALLY -- EVEN OF THOSE LAYERS CAN MOVE INDEPENDENTLY -- EACH OF THE LAYERS CAN MOVE INDEPENDENTLY AND DYNAMICALLY IN MANY DIRECTIONS, ALONG THE LONGITUDINAL PLANES OR TRANSVERSE PLANES. HOWEVER, WE ACTUALLY HAVE VERY LITTLE KNOWLEDGE ABOUT WHAT HAPPENS TO THE STRUCTURE AND FUNCTION OF THOSE TISSUES WHEN THEY ARE INJURED IN MUSCULOSKELETAL PAIN CONDITIONS. ALSO WE DO NOT KNOW THE THERAPEUTIC TREATMENT STRATEGIES THAT COULD BE HELPFUL TO RESTORE THE TISSUE FUNCTIONS STRUCTURALLY AND FUNCTIONALLY. SO IN THE NEXT TWO SLIDES, I'D LIKE TO BRING -- DISCUSS TWO EXAMPLES OF POTENTIAL TECHNOLOGIES THAT HELP US GAIN INSIGHT INTO THE MYOFASCIAL TISSUES IN MUSCULOSKELETAL PAIN. SO THIS FIRST EXAMPLE IS REALLY ILLUSTRATING TECHNOLOGY CALLED ULTRASOUND SONOELASTOGRAPHY, APPLYING INPUT TO THE SURFACE OF THE MYOFASCIAL TISSUES, THOSE TISSUES WILL MOVE, AND THE MOVEMENT OF THE TISSUES CAN BE DETECTED BY THE ULTRASOUND, BY ULTRASOUND TRANSDUCERS. AND AS YOU CAN SEE, THROUGH THIS SONOELASTOGRAPHY, THE SYMPTOMATIC AREAS APPEAR TO BE DARKENED SPACE IN THE DIAGRAM DUE TO RESTRICTED MOVEMENT OF THOSE TISSUES, IN COMPARISON TO THE MORE NORMAL SURROUNDING TISSUES. SO A LOT OF RESEARCH OBVIOUSLY IS NEEDED TO TRY TO UNDERSTAND WHETHER THOSE DARKENED AREAS IS ASSOCIATED OR CORRELATED WITH CLINICAL PALPATION OF THE MYOFASCIAL TRIGGER POINTS, AND CAN MONITOR PATHOPHYSIOLOGY OF THE CONDITION AS WELL AS BIOMARKERS FOR TREATMENT OF RESPONSES. THE SECOND EXAMPLE OF TECHNOLOGY IS CALLED MAGNETIC RESONANCE ELASTOGRAPHY, MRE. IT IS UTILIZING VIBRATION DEVICE TO DELIVER FORCE TO THE TISSUE. HOWEVER, IN THIS CASE THE DISPLACEMENT OF MYOFASCIAL TISSUE ARE OBSERVED, OR IMAGED, BY MAGNETIC RESONANCE IMAGING INSTEAD OF THE ULTRASOUND. THIS TECHNOLOGY HOLDS TREMENDOUS POTENTIAL FOR FUTURE -- FOR FURTHER DEVELOPMENT AND ENHANCEMENT, TO DETERMINE WHETHER THEY MAY BECOME POTENTIAL BIOMARKERS FOR PATHOLOY AND TREATMENT RESPONSES. IT IS IMPORTANT TO POINT OUT THAT THE TWO TECHNOLOGIES ONLY REPRESENT THE TIP OF THE ICEBERG TO EVALUATE MYOFASCIAL TISSUES IN THE MUSCULOSKELETAL PAIN. SUBSTANTIAL RESEARCH INVESTMENT IS NEEDED FOR US TO DEVELOP AND APPLY INNOVATIVE TECHNOLOGIES AND ASSESSMENT TOOLS FOR QUANTITATIVE EVALUATIONS OF MYOFASCIAL TISSUES IN MUSCULOSKELETAL PAIN. WITH THIS IMPORTANCE IN MIND I'D LIKE TO BRING TO YOUR ATTENTION THIS CONCEPT, RESEARH CONCEPT. THIS CONCEPT IS COMPOSED OF TWO-PHASED APPROACH, FIRST PHASE IS TECHNOLOGY DEVELOPMENT AND VALIDATION OF MYOFASCIAL LESIONS, DEVELOPING NEW TECHNOLOGIES OR EVALUATE THE ABILITY OF EXISTING TECHNOLOGIES TO VISUALIZE AND MEASURE THE LESIONS QUANTITATIVELY. AND WE WILL ALSO SUPPORT ASSESSMENT OF CORRELATION OF THOSE NEW QUANTITATIVE OBJECTIVE EVALUATIONS WITH CLINICAL PALPATION OF THE TISSUES OR OTHER TYPE OF CLINICAL SYMPTOMS AND DETERMINE THEIR SENSITIVITY, SPECIFICITY, TEST-RETEST STABILITY. IN THE SECOND PHASE STUDIES FOCUS ON TESTING POTENTIAL OF THOSE TECHNOLOGIES AND METHODS DEVELOPED IN THE FIRST PHASE TO SERVE AS BIOMARKERS FOR TREATMENT RESPONSES TO A VARIETY OF THERAPEUTICS FOR MUSCULOSKELETAL PAIN. FOR INSTANCE, ACUPUNCTURE ACTUALLY, DRY NEEDLING, LIDOCAINE INJECTION AND OTHER FORMS OF MANUAL THERAPIES OR YOGA HAVE BEEN COMMONLY USED TO MANAGE THE MYOFASCIAL PAIN CONDITIONS OR SYNDROMES WITH VERY LITTLE UNDERSTANDING OF THEIR MECHANISMS OF ACTION OR EFFICACY. SO IN THIS SPACE OF STUDY IT WOULD BE IMPORTANT TO SEE WHETHER THOSE METHODS DEVELOPED IN THE PHASE 1 CAN REALLY BE UTILIZED TO MONITOR PATHOPHYSIOLOGY AND TREATMENT RESPONSES TO THIS TYPE OF INTERVENTIONS. AND IN ADDITION, IT WOULD BE IMPORTANT TO INCORPORATE CUTTING-EDGE ARTIFICIAL INTELLIGENCE TOOLS AND COMPUTATIONAL MODELS INTO DEVELOPMENTS OF THOSE MEASURES TO ESTABLISH PREDICTIVE MODELS FOR THE PATHOPHYSIOLOGY OF THE MYOFASCIAL PAIN CONDITIONS AS WELL AS TREATMENT RESPONSES. WE BELIEVE THAT SCIENTIFIC ADVANCES IN THE PROPOSED AREA OF RESEARCH WILL TRANSFORM THE DIAGNOSIS AND TREATMENT OF A LARGE PORTION OF PAIN PATIENTS, AND AS WE SEARCH FOR EFFECTIVE AND NON-ADDICTIVE PAIN THERAPIES, AND THEY WILL MAKE SIGNIFICANT CONTRIBUTIONS TO THE REDUCTION OF OPIOID-BASED THERAPEUTICS FOR PAIN MANAGEMENT. WITH THAT I'D LIKE TO CONCLUDE THIS PRESENTATION AND THANK YOU FOR YOUR ATTENTION. I WELCOME YOUR COMMENTS AND QUESTIONS. >> DISCUSSION, QUESTIONS, COMMENTS? >> I HAVE A QUICK COMMENT. I'M WONDERING IF THIS INITIATIVE MIGHT BE OPEN TO THINGS THAT ARE DONE IN EAST ASIAN MEDICINE LIKE CUPPING, MOVING CUPS TO ALLEVIATE TISSUE IMMOBILITY IS COMMON, IS THAT CONSIDERED LIKE PART OF THE INITIATIVE? >> YES, I THINK ANY THERAPEUTIC OR INTERVENTIONS THAT WILL IMPACT THOSE TISSUES WOULD BE RELEVANT. >> JUST SOMETHING I DON'T SEE VERY MUCH IN THE RESEARCH LITERATURE AND I DON'T KNOW IF, YOU KNOW, INVESTIGATORS ARE EVEN AWARE OF THAT MODALITY AS BEING HELPFUL IN THIS TYPE OF CONDITION. >> CUPPING IS PRETTY FAMOUS BECAUSE OF MICHAEL PHELPS. [LAUGHTER] >> I DON'T SEE MUCH IN THE RESEARCH. >> I AGREE. I AGREE. >> YES? >> [OFF MICROPHONE] >> YEAH, I THINK THE NERVES WILL BE STUDIED IN THE CONTEXT OF THE NON-NEUROTISSUES, PART OF THE EFFORT IS TRYING TO HAVE SOME FOCUS ON THE NON-NEURAL ASPECT OF THE PAIN BECAUSE WE'VE BEEN SO FOCUSED ON THE NEURAL ASPECT, AND THERE'S A LARGE GAP AREA THAT NEEDS TO BE FILLED. >> NEVER ONE TO SHY ABOUT GOING ON THIN ICE, I GUESS THE ONLY CONCERN I HAVE, THIS IS GREAT STUFF, WE'VE TALKED ABOUT THIS FOR SO MANY YEARS ABOUT THE NEED TO BETTER UNDERSTAND, THIS MIGHT BE AS BIG A MYSTERY AS THE MICROBIOME AS FAR AS WHAT THE FASCIA DOES. I JUST, FOR CRITICS AND SKEPTICS, I WORRY MAYBE YOU AND HELENE COULD HELPF WE'RE OVERLY FOCUSED ON SORT OF MEGA QUANTITATIVE MEASURE. IS IT POSSIBLE WE OVERLOOK MUCH MORE SUBTLE SIGNALING ACROSS FACIAL PLANS AND WE WOULD BE SEEN, IF IT WAS NEGATIVE, INVALIDATING THE ROLE OF FASCIA, IF YOU FOLLOW WHAT I'M SAYING. >> YOU'RE WONDERING, YOU THINK THE ACTUAL ABNORMALITIES MAY BE MORE SUBTLE THAN WHAT WE'RE DETECTING BY PALPATION. >> WELL, I'M THINKING ABOUT, YOU KNOW, YOUR NOW FAMOUS RAT YOGA STUDIES WHERE YOU SAW THAT THE INVESTITURE DOWN TO THE MUSCLE CELL, FASCICLE, GOT TRANSLATED INTO DOWNREGULATION OF INFLAMMATION IN TISSUE. I'M NOT SURE THAT WOULD BE PICKED UP BY SOMETHING LIKE THIS. WHAT I'M CONCERNED ABOUT IS ONLY THAT THERE BE CAVEATS ON THIS WORK THAT SAYS THIS DOESN'T DEFINE THE TOTALITY OF WHAT THIS MIGHT BE DOING. DO YOU FOLLOW WHAT I'M SAYING? >> THAT'S FAIR. I THINK WE'RE STARTING HERE FROM THE PREMISE THAT IF YOUR HANDS CAN FEEL SOMETHING, THAT FEELS MORE STIFF OR HARDER OR DIFFERENT COMPARED WITH SURROUNDING TISSUE, WE SHOULD HOPEFULLY BE ABLE TO MEASURE THAT AND SO FAR WE HAVEN'T FOUND A GOOD WAY TO MEASURE IT. SO THAT'S REALLY KIND OF STARTING AT A REALLY BASIC FUNDAMENTAL SORT OF VERY SIMPLE LEVEL. I AGREE THERE MAY BE MUCH MORE SUBTLE THINGS GOING ON IN THESE TISSUES AS WELL, AND IN FACT ONE OF THE THINGS THAT WE ALSO DISCUSSED AS PART OF THE WORKSHOP, RIGHT, BECAUSE WE'RE GOING TO HAVE A WORKSHOP ABOUT THIS, LOOKING AT METABOLIC MEASURES, LOOK AT MASS SPEC, FOR EXAMPLE, WE'LL LOOK -- NOT MASS SPEC, SPECTROSCOPY, IMAGING, THERE'S ONE-SIDED MRI TECHNIQUES, NOT EXISTING NOW, THERE'S A LOT OF OTHER TECHNIQUES THAT COULD LOOK AT MORE SORT OF BIOCHEMICAL BUT STILL -- >> YEAH. >> WE WANT THESE TO BE NON-INVASIVE. THAT'S IMPORTANT. NOT BIOPSIES. >> I'M WITH YOU. AGAIN, I THINK THIS IS TERRIFIC. THIS IS MORE I WANT TO PROTECT THE AREA FROM ATTACKS THAT MIGHT COME OUT FROM THIS. FOR EXAMPLE, PALPATION, YOU KNOW, WE LEARN A LOT ON BREAST SELF EXAMINATION AND PHYSICIAN PROVIDER EXAMINATIONS OF BREAST MASSES TO KNOW THAT WHAT YOU THOUGHT YOU FELT WASN'T THERE. OR WHAT YOU DIDN'T FEEL WAS THERE. SO THERE'S A LOT OF FALSE NEGATIVES, FALSE POSITIVES IN THIS WORLD OF PALPATION, TO GO BACK INTO THIS WORK AND THE WORK OF PEOPLE WITH DRY NEEDLING, I'M WORRIED THAT VERY SUBTLE SIGNALING ACROSS FACIAL PLANES MIGHT BE STIMULATING SPASM AND OTHER TRIGGER POINT EVENTS THAT REALLY ORIGINATE SOMEWHERE ELSE. AND WE'RE NOT GOING TO BE ABLE TO PICK THAT UP NECESSARILY BY SOMETHING LIKE THIS. THAT'S MY COMMENT. >> THAT'S TRUE. IT'S A VERY GOOD POINT. >> I JUST WANT TO GO ON EVEN THINNER ICE, WHICH IS THAT ON A CLINICAL SIDE, YOU KNOW, WHEN YOU'RE PALPATING OR LET'S SAY WHEN AN ACUPUNCTURIST IS PALPATING, THERE'S THE CONCEPT OF WHAT'S THE ENERGY FLOW IN THE AREA, RIGHT? AND SO I THINK JUST TO ERIC'S POINT, IT IS A BEAUTIFUL IDEA, AND YOU WOULDN'T WANT THE NOTION TO BE EXTRACTED FROM THIS THAT IF YOU'RE PALPATING AS A CLINICIAN AND THERE'S NO EVIDENCE OF A VISIBLE OR MYOFASCIAL OR EVEN BIOCHEMICALLY MEASURABLE MYOFASCIAL LESION, THAT YOUR PALPATION IS NECESSARILY NOT VALID AS A MEANS TO STEER CLINICAL TREATMENT. AND I KNOW THAT'S -- YOU KNOW -- >> CERTAINLY WOULDN'T WANT TO IMPLY THAT, THAT THE NEGATIVE TISSUE IS NORMAL, BUT TO START AT GROSS ANATOMICAL LEVEL, YOU HAVE TO START SOMEWHERE, RIGHT? AND RIGHT NOW WHEN YOU THINK ABOUT IT, I MEAN, HOW MANY -- I THINK THE BREAST EXAM EXAMPLE IS VERY GOOD, BECAUSE -- BUT, YOU KNOW, TECHNIQUES, FOR EXAMPLE, DEVELOPED LIKE, YOU KNOW, RADIOLOGICAL TECHNIQUES, SONOGRAPHY, TO DETECT PALPABLE LESIONS, THAT'S HOW THEY STARTED. THE TECHNIQUES GOT SO GOOD THEY WERE ABLE TO DETECT NON-PALATABLE LESION BUT YOU HAD TO START WITH PALPABLE LESION TO GUIDE WHERE YOU'RE GOING TO LOOK. I HAVE A SENSE THAT IT WOULD BE GREAT IF WE COULD GET TO THESE MORE SUBTLE THINGS, BUT I WOULD ARGUE THAT STARTING WITH THE PALPABLE THINGS MIGHT BE A GOOD, YOU KNOW, FIRST STEP. >> I WASN'T ARGUING THAT IT WOULDN'T. JUST THAT THINKING ABOUT IT FROM THE POINT OF VIEW OF HOW WE GET CRITIQUED IN SOME PARTS OF THE ACADEMIC WORLD. >> GOOD POINT. >> DOES THIS MEAN NCCIH THINKS IF IT'S NOT POLL -- NOT VISIBLE OR MEASURABLE THAT IT'S NOT REAL >> (OFF MIC.). >> YOU HAVE TO TELL THEM. >> I KNOW THE THEORIES NOT CLASSIFIED AS SCIENTIFIC BUT IF WE LOOKED IN THAT CONTEXT, CLASSIC EXAMPLE, STAGNATION VERSUS BLOOD STASIS, SO IF WE COULD USE THAT AS A CONCEPTUAL FRAMEWORK WE COULD SUBSTANTIATE THE DIFFERENTIATION BETWEEN PALPABLE AND NON-PALPABLE, JUST A SUGGESTION. >> TWO THINGS. ONE, I LOVE THE IDEA OF DEVELOPING NEW TECHNOLOGIES BECAUSE I THINK WE HAVE A LOT OF INNOVATION THAT COULD HAPPEN THERE AND GUIDE AN RFA TO WHAT NEW TECHNOLOGIES THAT COULD BE COMBINED, NOT NECESSARILY EVALUATE EXISTING BUT PROBABLY COMBINATION OF TECHNIQUES, NEW DEVELOPMENT PLUS WHAT WE HAVE DEVELOPED BEFORE, AND SOMETIMES WE GO IN EITHER DIRECTION BUT I WOULD HOPE WE COULD INCORPORATE BOTH NEW DEVELOPMENTS AND EXISTING TECHNOLOGIES AND THE IDEA THAT YOU ARE DOING A LOT OF DATA ANALYSIS, HAVING A DATA COMPONENT, WASN'T SURE WHY IT'S NOT ALSO IN PHASE 1 BECAUSE I FEEL YOU WILL GET SOME INFORMATION THERE AND WILL BE ABLE TO USE COMPUTATIONAL TENGE NECKS TO GO TO -- TECHNIQUES TO GO TO PREDICTIVE MODELING, HOW THIS COULD BE HELPFUL, PEOPLE THAT COULD POTENTIALLY GET IT FOR WHATEVER REASONS. >> YOU SHOULD PUT IT IN PHASE 1. >> I DIDN'T MEAN TO LEAVE OUT THOSE COMPUTATIONAL ASPECTS IN THE PHASE 1. IT WAS JUST TRYING TO EMPHASIZE IN THE PHASE 2 AS WELL. WE HAVE A PRETTY BIG TEAM ACTUALLY, TRANS-NIH TEAM WORKING ON THIS TOGETHER, INCLUDING NIBIB, WHICH IS CO-LEADING THIS EFFORT WITH US. AND AS WELL AS NIAMS AND NINDS, NICHD, AND NIDCR. SO WE HAVE A GOOD TEAM OF PROGRAM OFFICERS AND EXPERTS INVOLVED AS WE PLAN WORKSHOP AND HOPEFULLY SUBSEQUENT INITIATIVE. >> OKAY. BEING MINDFUL OF TIME, I'D LIKE TO ENTERTAIN A POCKETS OF SLOWING FOR APPROVAL OF THIS CONCEPT, SO MOVED. SECONDED. OKAY. SO I'LL TAKE A VOTE. THOSE IN FAVOR OF APPROVAL OF THIS CONCEPT PLEASE INDICATE BY RAISING YOUR HAND AND WE'LL GET A COUNT. OKAY. AND NOW THOSE ON THE PHONE, DR. HENSEL? >> AS A D.O. AND OMT, I ENTHUSIASTICALLY APPROVE THIS. >> THANK YOU. DR. TIMERMAN? >> APPROVE. >> DR. YAY? >> AS WELL. >> WE'LL MARK THIS ALSO AS UNANIMOUS. WE'LL NOW GO TO THE NEXT CONCEPT, ALSO GOING TO BE PRESENTED BY DR. CHEN, BLUEPRINT INITIATIVE CONCEPT, FUNCTIONAL NEURAL CIRCUITS OF INTEROCEPTION. >> THANK YOU. SO, YES, NOW IT'S MY SECOND PRESENTATION ON THIS BLUEPRINT CONCEPT TO GIVE BACKGROUND, THIS INITIATIVE REPRESENTS COLLECTIVE EFFORT OF A VERY LARGE TEAM OF PROGRAM OFFICIALS ACROSS MANY NIH INSTITUTES AND CENTERS AND OFFICES INVOLVED IN THE NIH BLUEPRINT FOR NEUROSCIENCE CONSORTIUM, PRESENTING TODAY A CONCEPT, RESEARCH INITIATIVE CONCEPT, FUNCTIONAL -- OH, FUNCTIONAL NEURAL CIRCUITS OF INTEROCEPTION, AS DEFINED BY THIS INITIATIVE REPRESENTS PROCESSES BY WHICH THE BODY SENSES, INTERPRETS, INTEGRATES AND REGULATES SIGNALS FROM WITHIN ITSELF. WE ACTUALLY CONSIDERED SKIN AS THE BOUNDARY OF INTEROCEPTION, BASICALLY SENSATION AND REGULATION OF ANY ORGAN WITHIN SKIN CONSIDERED PART OF INTEROCEPTION, WHEREAS IT IS IMPORTANT TO POINT OUT THAT INTEROCEPTION IS NOT A REPRESENTATION OF THE EXTERNAL WORLD THROUGH SOMATO SENSATION, VISION, AUDITION, OLFACTION OR TASTE. SO, LAST YEAR AS YOU HEARD FROM PREVIOUS COUNCIL MEETINGS THAT WE HAD THIS LARGE TEAM OF NIH INTEROCEPTION WORKING GROUP ORGANIZED A WORKSHOP IN APRIL LAST YEAR AND THE WORKSHOP TITLE IS SCIENCE OF INTEROCEPTION AND ITS ROLES IN NERVOUS SYSTEM DISORDERS. THE MANY I.C.s INVOLVED IN THIS EFFORT, ALMOST ALL OF THEM ARE INVOLVED. AND THE -- THE WITHOUT GOING INTO DETAILS OF THE WORKSHOP, THE BEAUTIFUL PAPER DEMONSTRATES THE CONCEPT AND RESEARCH, CUTTING-EDGE RESEARCH ON INTEROCEPTION, PUBLISHED AS A RESEARCH ARTICLE IN "NATURE" LAST OCTOBER BY ONE OF THE SPEAKERS OF THE WORKSHOP, DR. PAUL KENNY AND COLLEAGUES DEMONSTRATING THAT THERE'S A VERY INTRICATE INTERPLAY BETWEEN THE BRAIN AND THE BODY THROUGH VASCULAR SYSTEM DELIVERY SIGNALS AS WELL AS A NEURAL VAGAL PATHWAY FROM THE BRAIN TO THE PANCREAS TO REGULATE THE BLOOD SUGAR LEVELS IN THE CONTEXT OF DIABETES. ALSO DEMONSTRATES A SURPRISING IMPACT OF THIS INTEROCEPTION PROCESS ON BRAIN FUNCTION INVOLVING NICOTINE DEPENDENCE AND NICOTINE ADDICTION. THIS IS THE EPITOME OF WHAT WE WERE LOOKING FOR IN TERMS OF RESEARCH INVOLVED IN INTEROCEPTION. IN AN EFFORT TO UNDERSTAND WHAT THE CURRENT NIH PORTFOLIO ON INTEROCEPTION RESEARCH IS LIKE AND HOW DOES IT COMPARE TO WHAT WE'VE BEEN DISCUSSING IN THE WORKSHOP LAST YEAR, DR. ANGELA ARESDOFF AND DR. DANA FROM OFFICE OF BEHAVIORAL AND SOCIAL SCIENCE RESEARCH IN THE OFFICE OF DIRECTOR OF NIH DID A VERY NICE PORTFOLIO ANALYSIS USING THE TERM, MEDICAL TERMS INVOLVING THE KEY CONCEPT OF INTEROCEPTION, FOR NIH GRANTS IN THE PAST TEN YEARS AS WELL AS WORD CLOUD ANALYSIS OF WORKSHOP SUMMARY AS YOU CAN SEE CURRENT NIH PORTFOLIO INTEROCEPTION IS HEAVY ON THERAPEUTICS AND REGULATION BUT ACTUALLY LACKING THE KEY CONCEPT ABOUT INTEROCEPTION RELATED TO THE BRAIN AND BODY SIGNALING AND CONNECTIONS. AND THIS SORT OF GAP OF KNOWLEDGE AT LEAST IN NIH PORTFOLIO CAN BE EXPLAINED BY TWO ONGOING MAJOR NIH TRANS-NIH INITIATIVES. ONE IS THE WELL KNOWN BRAIN INITIATIVE, WHICH ACTUALLY EXCLUSIVELY FOCUSES ON THE SCIENCE OF THE BRAIN, AND TECHNOLOGY OF THE BRAIN. AND THE OTHER ONE IS A COMMON FUND, ONGOING COMMON FUND PROJECT, AND THAT'S -- BRAIN INITIATIVE IS ABOUT LIKE $4,000 " MILLION OVER 10 YEARS AND SPARC, THE LOCAL ORGAN LEVELS. AND AS YOU CAN SEE THERE'S -- THOSE TWO LEFT OUT THE CONNECTION BETWEEN THE BRAIN AND BODY. AND THIS GAP IS WHAT WE WERE HOPING TO ADDRESS THROUGH THIS BLUEPRINT INTEROCEPTION INITIATIVE. THE SCOPE OF THIS INITIATIVE WILL -- DUE TO BUDGET CONSTRAINS WILL FOCUS ON NEURAL PATHWAYS, SPECIFICALLY THE SPINAL PATHWAYS AND CRANIAL VAGAL NEURAL PATHWAYS CONNECTING THE BRAIN AND REST OF THE BODY, AND WILL INCLUDE ASCENDING AND DESCENDING PATHWAYS. AND IN FACT ZOOMING INTO THE SPECIFIC PERIPHERAL GANGLIA RESIDING BETWEEN PERIPHERAL ORGANS AND THE BRAIN TO -- THE PRIMARY SENSOR AND EFFECTOR COMMUNICATOR BETWEEN THE BRAIN AND THE BODY, AND THE SPECIFIC RESEARCH TOPICS THAT WE WOULD LIKE TO SUPPORT THROUGH THIS INITIATIVE INCLUDE BUT NOT RESTRICTED TO THE FOLLOWING TOPICS, INCLUDE CELL-TYPE CHARACTERIZATION OF THE PRIVILEGE WALL GANGLIA INVOLVED IN INTEROCEPTION, IDENTIFICATION OF SPECIFIC GANGLIA RESPONSIVE TO INTEROCEPTION SIGNALS, ANATOMICAL MAPPING OF NEURAL CIRCUITS INVOLVED IN INTEROCEPTION, AND FUNCTIONAL CHARACTERIZATION CIRCUITS AT PHYSIOLOGIC AND BEHAVIORAL LEVELS. THE TEAM HAS AGREED IN THIS PHASE OF EFFORT TO FOCUS PRIMARILY ON ANIMAL MODEL RESEARCH TO ACHIEVE THIS SCIENTIFIC GOAL. SO THIS IS THE BASICALLY NUTSHELL OF THE INITIATIVE. AND I WANT TO CONCLUDE MY PRESENTATION HERE AND WELCOME YOUR QUESTIONS AND COMMENTS. >> QUESTIONS, COMMENTS? BOTH? >> I HAVE A QUESTION. CAN YOU SAY A LITTLE BIT MORE ABOUT WHY THE FOCUS ON THE ANIMAL MODELS TO BEGIN WITH? >> IT'S -- IT WAS MOSTLY BUDGETARY CONSTRAINT. WE WERE RAISING FUNDS -- I DON'T KNOW IF I CAN TALK ABOUT THAT. ANYWAY, THE WORKSHOP IDENTIFIED MANY RESEARCH GAPS, BOTH ANIMAL MODEL LEVEL BASICALLY AS WELL AS THE HUMAN CLINICAL RESEARCH LEVELS. BUT THE -- I THINK THE TEAM HAS DECIDED TO FOCUS ON THE BASIC SCIENCE FIRST TO RAISE THE BOAT SO WE'LL HAVE A BETTER UNDERSTANDING OF THE BLUEPRINT OF THE CIRCUITS AND THAT WILL HOPEFULLY THEN BE SUPPORTED IN FUTURE EFFORTS ON THE MORE CLINICAL AND TRANSLATIONAL EFFORTS ON THE TOPICS. I WANT TO EMPHASIZE I'M HOPING THIS IS THE BEGINNING OF THE TOPIC, NOT THE END OF IT. SO IT'S JUST THE FIRST EFFORT WE'RE TRYING TO MAKE. >> I THINK IT'S FANTASTIC THAT THE TOPIC IS PICKED UP. WONDERFUL. I JUST WANT TO MENTION THAT INTERIOR INSULA, FOR INTEROCEPTION, IT'S UNDERDEVELOPED, FOR THE SUPERIOR AREAS, AND I DON'T KNOW HOW MUCH THE LOWER MAMMALS RESEARCH WOULD CONTRIBUTE, JUST WONDERING. >> ANIMAL MODELS ARE NOT LIMITED TO LOWER LEVELS, NON-HUMAN PRIMATES WORK AS WELL. >> YEAH, I WANT TO WEIGH IN AND SAY I THINK THIS IS TERRIFIC AS WELL. IT'S UNFORTUNATE THAT THE ORIGINAL BRAIN AND SPARC PROJECT DID NOT CONNECT MIND AND BODY. I THINK THAT'S KIND OF AN OBJECT LESSON IN WHAT WE'RE ALL FACING. I WOULD HOPE, AGAIN, TO GO BACK TO FASCIA DISCUSSION THAT THIS -- YOU SAID YOU'RE GOING TO GO FURTHER WITH THIS. ONE OF THE AREAS I THINK THAT IS WORTH -- I MEAN A LOT OF WHAT THE WORK LOOKS LIKE IT'S GOING TO FOCUS ON IS WHAT WE ALREADY KNOW ABOUT CONNECTIONS. BUT SOME OF THE THINGS WE DON'T KNOW, FOR EXAMPLE, THE NEURAL CONNECTION BETWEEN THE BRAIN AND BONE MARROW, THE SPLEEN, REGULATOR OF INFLAMMATION, SO IF A FUTURE EFFORT IS ALSO TO LOOK AT SOME UNRECOGNIZED BUT NOVEL CONNECTIONS, THAT MAYBE MEDIATING AREAS THAT WE DON'T HISTORICALLY THINK ABOUT, WE THINK ABOUT GUT PROBLEMS AND THINK ABOUT -- >> IT WOULD BE GREAT IF SOMEONE WOULD COME UP WITH A PROPOSAL TO STUDY NEURAL CONNECTION BETWEEN BRAIN AND BONE MARROW. THIS EFFORT SHOULD BE ABLE TO HELP TO DISCOVER, AND SO I DON'T MEAN TO SAY WE WANT TO FOCUS ON THINGS ALREADY KNOWN, THAT'S NOT THE IDEA. THE IDEA IS TO DISCOVER NEW CIRCUITS, CONNECTIONS HERE. >> YEARS AGO I WAS ON A TEAM THAT FOUND VASCULAR CHOLINE RECEPTORS ON RED BLOOD CELLS, WHAT THE HELL ARE THEY DOING THERE? THERE ARE NO NERVES IN THE BONE MARROW. WELL, MAYBE THERE ARE. THERE ARE. AND MAYBE THIS IS PART OF A GENERALIZED UPREGULATION-DOWNREGULATION SYSTEM WE NEVER RECOGNIZED. >> ABSOLUTELY. >> ONE MORE QUESTION. PAIN I SAW IN THIS GRAPH, OTHER WORDS WERE SHOWN. >> PAIN? >> THE WORD "PAIN" WAS VERY SMALL, PRINTED. >> YES. >> IS THAT CONSIDERED AS PART OF THE INTEROCEPTION, LIKE IS THERE A CONNECTION BETWEEN MYOFASCIAL PAIN AND INTEROCEPTION? THAT WOULD BE MY QUESTION. >> PAIN IS THE TRICKY TOPIC HERE BECAUSE IT DEPENDS WHETHER -- I GUESS IT DEPENDS WHETHER IT GOES THROUGH SOMATOSENSATION, SENSE THE EXTERNAL ENVIRONMENT, OR LOOKING AT INTEROCEPTIVE, IT CROSSED INTEROCEPTION AND WILL FIT WITH THIS EFFORT, WITH SOME OF THOSE MIGHT FALL INTO THE EXOCEPTION, IT'S UP TO THE INVESTIGATORS TO DEFINE THAT CLEARLY. >> A COMMENT ON THAT, GREAT QUESTION. IT WAS A LOT OF DISCUSSIONS ABOUT THAT AT THE INTEROCEPTION WORKSHOP. WHERE PAIN FITS, YOU KNOW, IT'S EVERYWHERE, RIGHT? BUT THE ONE THING THAT WE'RE REALLY MISSING IN MUSCULOSKELETAL PAIN FIELD IS A BETTER UNDERSTANDING OF PROPRIOCEPTION, WHEN WE THINK OF PROPRIOCEPTION AND TEST IT CLINICALLY WE REMOVE JOINTS UP AND DOWN, THAT'S WHAT DOCTORS DO. BUT THERE'S SO MUCH MORE TO SENSATION FROM MUSCULOSKELETAL TISSUES. AND HOW THOSE SENSATIONS THAT WE GET IN THE ABSENCE OF ABNORMALITIES, JUST NORMALLY, HOW DO SENSATIONS CHANGE, WHAT IS THE EQUIVALENT OF ALLODYNIA IN DEEP TISSUES AND DEEP CONNECTIVE? WE DON'T KNOW. THESE ARE ALL QUESTIONS THAT WILL BE RELEVANT TO NORMAL PHYSIOLOGY AND PATHOPHYSIOLOGY. SO I DON'T THINK PAIN NECESSARILY EITHER BELONGS OR DOESN'T BELONG IN THERE. IT WILL NATURALLY FLOW FROM IT I THINK. >> I HAVE A REALLY CONCRETE QUESTION. I MEAN, ONE OF THE THINGS, HELENE COULD HAVE SAID THIS AFTER YOUR PRESENTATION, REALLY IMPRESSIVE ABOUT WHAT NCCIH HAS DONE IS TO BE VERY STRATEGIC IN LEVERAGING RELATIONSHIPS WITH THE OTHER I.C.s IN THAT, YOU KNOW, THE AMOUNT OF IMPACT FOR A RELATIVELY SMALL CENTER IS JUST REALLY CRAZY IMPRESSIVE. I KNOW PART OF WHAT WE WERE HEARING IS THERE WERE BUDGETARY CONSTRAINTS ON THIS, SO THESE COULD BE MORE EXPANSIVE. BUT ARE THESE PROJECT CONCEPT CLEARANCES THAT ARE I'M ASSUMING BROADER THAN NCCIH? THIS IS INVOLVING ALL THE ICs, RIGHT? >> I DON'T KNOW HOW MUCH WE'VE CAN SAY ABOUT THE BUDGET BUT IT IS A TRANS-NIH EFFORT. >> [OFF MICROPHONE]. >> YEAH, OKAY. >> MYOFASCIAL PAIN INITIATIVE COULD BE PART OF THE HEAL INITIATIVE, THE WORKSHOP IS, SO IF THIS, YOU KNOW, COULD POTENTIALLY BE PART OF THE HEAL INITIATIVE, WE DON'T KNOW YET. >> I WOULD JUST SAY -- HOW DO I WANT TO SAY THIS? ON THE LAST PROJECT CONCEPT YOU WERE SAYING LET'S START WITH THE MOST CONCRETE, BUT ALSO I THINK NCCIH THINKS MORE EXPANSIVELY THAN SOMETIMES SOME OF THE OTHER INSTITUTES, WAYS TO REALLY PUSH THE ENVELOPE SOME OF WHAT PEOPLE ARE BRINGING INTO THIS, FROM THIS DISCUSSION. >> I THINK WEN SAID IT BEST. THIS IS THE FIRST STEP. AND WE'RE LOOKING FOR A LONG JOURNEY. >> OKAY. SO, I'D LIKE TO ENTERTAIN A MOTION FOR APPROVAL OF THIS CONCEPT. SO MOVED. SECOND? ANY FURTHER DISCUSSION ON THE MOTION? WE'LL TAKE A VOTE THEN. ALL IN FAVOR OF APPROVING THE MOTION PLEASE INDICATE BY RAISING YOUR HAND. HOLD IT UP SO WE GET A COUNT. OKAY. AND THEN ON THE PHONE, DR. HENSEL? >> I APPROVE. >> DR. TIMERMAN? >> I APPROVE. >> DR. YAY? >> I APPROVE. >> THANK YOU. OKAY. WE'LL MARK THAT ALSO AS UNANIMOUS. AND GO TO THE FOURTH AND LAST CONCEPT PRESENTATION FOR THIS MEETING, BY DR. SABRI, UNDERLYING MECHANISMS OF FORCE-BASED MANIPULATIONS, HIGH PRIORITY RESEARCH NETWORKS. >> OKAY. GOOD MORNING, EVERYONE. I'M THE LAST ONE, SO THEN YOU GET TO HAVE LUNCH. I'M MERAV SABRI, PROGRAM DIRECTOR IN THE BASIC AND MECHANISTIC -- SORRY, IN THE BASIC AND MECHANISTIC RESEARCH BRANCH, NCCIH, PRESENTING A CONCEPT INITIATIVE ON THE UNDERLYING MECHANISMS OF FORCE-BASED MANIPULATIONS, HIGH PRIORITY RESEARCH NETWORKS. FORCE-BASED MANIPULATIONS REFERS TO PASSIVE APPLICATIONS OF MECHANICAL FORCE TO THE OUTSIDE OF THE BODY WITH THERAPEUTIC INTENT. RATHER THAN ACTIVE MOVEMENT OR EXERCISE. EXAMPLES OF FORCED-BASED MANIPULATIONS INCLUDE LIGHT TOUCH, PRESSURE, THRUST, NEEDLING. THE RANGE OF APPLIED FORCES IN MANIPULATIONS IS DIVERSE. FORCES APPLIED IN SPINAL MANIPULATIONS ARE ABOUT 1,000 TIMES GREATER THAN THOSE IN ACUPUNCTURE NEEDLING, AND FORCES IN MASSAGE ARE INTERMEDIATE BETWEEN THE TWO. TISSUES RESPOND TO DIFFERENT FORCES. FUNDAMENTAL UNDERSTANDING OF THE MECHANISMS BY WHICH FORCE-BASED MANIPULATIONS EXERT THEIR EFFECT IS LACKING. IN THE FIELD OF NEUROSCIENCE A LARGE BODY OF RESEARCH HAS NEURAL SYSTEMS INVOLVED IN FORCE-BASED MECHANOSENSATION. HOWEVER, SCIENTISTS IN THE FIELD HAVE BEEN COMPLETELY UNAWARE OF THE RELEVANCE OF THE WORK TO THE SCIENCE BEHIND MANUAL THERAPIES, SUCH AS MASSAGE AND SPINAL MANIPULATION. IN AN EFFORT TO BUILD A COMMON LANGUAGE AND FACILITATE COLLABORATIONS AND TRANSLATION, NCCIH IN COLLABORATION WITH DR. NOD OF NINDS PLANS TO ORGANIZE A WORKSHOP TO BRIDGE THE GAP, WE HELD THE WORKSHOP ON NEURAL CIRCUITRY LAST SEPTEMBER. THE WORKSHOP WAS CO-SPONSORED BY NICHD AND CMRR, OTHER NIH PARTNERS INCLUDED NIBIB AND NIA. THE TWO-DAY MEETING FOLLOWED A ROUNDTABLE FORMAT. DR. ELLEN LUMPKIN AND BRANFORD, YOU CAN SEE THEM BOTH IN THE CIRCLE. PARTICIPANTS INCLUDED NIH ORGANIZERS, A SMALL GROUP OF INVITED EXPERTS, FROM THE MANUAL THERAPY AND MECHANOSENSATION FIELDS. THE WORKSHOP GOALS WERE TO IDENTIFY RESEARCH GAPS AND BARRIERS, TO DISCUSS NEW RESEARCH OPPORTUNITIES FOR THE FIELD, PROMOTE COLLABORATIONS AMONG NEUROSCIENTISTS, MANUAL THERAPIST, PHYSIOLOGIST, MATHEMATICIANS AND ENGINEERS. LASTLY DEVELOP AND ENCOURAGE MOST NEEDED COMMON TERMINOLOGY. THE FOLLOWING SCHEMATIC SUMMARIZES THE DIFFERENT ACTIVE INGREDIENTS ESSENTIAL TO RESEARCH FRAMEWORK MODEL AS DISCUSSED AT THE WORKSHOP. THE FRAMEWORK INCLUDES INTEROCEPTIVE PATHWAY BEGINNING WITH SIGNALS IN THE CONNECTIVE TISSUE AND MUSCLES, DETECTED AND TRANSMITTED INTO THE BRAIN FOR INTEGRATION AND PROCESSING. THE SIGNALS WOULD BE FURTHER TRANSMITTED IN THE DESCENDING PATHWAYS BACK TO PERIPHERAL TISSUES THROUGH THE SPINAL CORD. THIS IS THE INTEROCEPTIVE CIRCUIT. THE SECOND MAJOR COMPONENT OF THIS FRAMEWORK IS HOW FORCE-BASED MANIPULATION CAN THEN REGULATE THE CIRCUITS. THE MANIPULATION IS TYPICALLY DELIVERED BY A PRACTITIONER WHO CAN INFLUENCE THE CIRCUITS FROM TWO DIRECTIONS. ONE DIRECTION IS THROUGH THE DELIVERY OF FORCE TO THE PERIPHERAL MUSCLES AND TISSUES, AND THE OTHER IS THROUGH INTERACTIONS WITH THE PATIENTS BY CREATING A PSYCHOSOCIAL CONTEXT AND EXPECTATION. THE CONTEXT CAN DIRECTLY INFLUENCE THE PATIENT'S BRAIN ACTIVITY. THE SOCIAL INTERACTION CAN BE PROJECTED BACK THROUGH DESCENDING PATHWAYS TO INFLUENCE THE PERIPHERAL TISSUE ACTIVITY. THE ROUNDTABLE IDENTIIED GAPS IN OPPORTUNITIES IN THE VARIOUS COMPONENTS OF THIS RESEARCH FRAMEWORK. SPECIFICALLY, THE MECHANICAL FORCE AND RESPONSE TO IT, HOW EXTERNAL FORCE AND PSYCHOSOCIAL CONTEXT AFFECT NEURAL CIRCUITS OF FORCE-BASED MANIPULATION, THE NEED FOR COMPUTATIONAL MECHANISTIC MODELS THAT INCLUDE HISTORICAL FACTORS, SOCIAL FACTORS, AFFECT, MOOD, THE TECHNOLOGY NEEDS TO ADVANCE THE RESEARCH, AND LASTLY THE CHALLENGES FOR TRANSDISCIPLINARY EFFORTS. IN RESPONSE TO THESE CHALLENGES AND GAPS, WE WOULD LIKE TO PROPOSE AN INITIATIVE CONCEPT FOR ESTABLISHMENT OF INTERDISCIPLINARY RESEARCH NETWORKS TO FOCUS ON DEVELOPING RESOURCES BY REFINING AND TESTING KEY CONCEPTS THAT WILL ADVANCE AND FURTHER SUPPORT THE STUDY OF FORCE-BASED MANIPULATION. THE SCIENTIFIC SCOPE OF NETWORKS WILL INCLUDE THE FOLLOWING HIGH PRIORITY RESEARCH AREAS. TERMINOLOGY AND MEASUREMENTS OF FORCE-BASED MANIPULATION, MECHANISTIC RESEARCH ON THE NEURAL CIRCUITRY OF FORCE-BASED MANIPULATION, CONTEXT CAL PSYCHOSOCIAL AND EXPECTATIONS EFFECT OF FORCE-BASED MANIPULATION, BIOMARKERS AND LASTLY TECHNOLOGY AND METHODOLOGY DEVELOPMENT FOR MECHANISTIC STUDIES ON THE TOPIC. WITH THAT I WOULD LIKE TO THANK YOU FOR YOUR ATTENTION AND I'LL >> THE FLOOR IS OPEN. >> I HAVE A QUESTION FROM MY WORK EXPERIENCE, AS A MANUAL THERAPIST. ATTENTION, STYLE OF ATTENTION, QUALITY OF ATTENTION IS AN ELEMENT OF CONTEXT FRAME THERE? >> YES, ABSOLUTELY. AND DR. BUSHNELL IN OUR INTRAMURAL PROGRAM HAS SOME RESEARCH TO SHOW THAT ATTENTION AND DESTRUCTION IS AN INTEGRAL PART OF THE CIRCUITRY. >> AND I'M SORRY THAT CHEN JEN WANG IS NOT HERE BUT THIS LENDS ITSELF TO LOOKING AT THE ROLE OF THE PROVIDER. WE TALK ABOUT THAT WITH ACUPUNCTURE AND YOGA. THIS SEEMS TO ME TO BE A REALLY GOOD AREA THAT YOU COULD ISOLATE THE EFFECT OF PROVIDER AND INTERACTION, HUMAN DIMENSION, FROM THE SIMPLE MECHANICAL FORCE. AND MAY GET AT A LOT OF STUFF WE'RE STRUGGLING WITH AROUND THAT. >> YES, ABSOLUTELY. THAT WOULD TAP INTO TWO DIFFERENT CIRCUITRIES. >> I WANT TO INVITE DR. HENSEL AND DR. EVANS IF THEY HAVE COMMENTS? >> YES, I DO. DR. HENSEL. I'M CURIOUS ABOUT A COUPLE OF THINGS. NUMBER ONE, IT SOUNDED LIKE IN TALKING ABOUT THE WORKSHOP THAT YOU MENTIONED BRIDGING TWO PROFESSIONS, I WAS CURIOUS WHAT THOSE WERE, IT SEEMED LIKE IT WAS CHIROPRACTIC CARE, IS THAT ONE OF THEM? >> MANUAL THERAPIES IN GENERAL, SO CHIROPRACTIC, PHYSIOTHERAPIST, OSTEOPATH. >> OKAY. WERE THERE ANY OSTEOPATHIC PHYSICIANS AT THAT FOCUS SESSION? >> I THINK WE HAD A REPRESENTATIVE, YES. >> OKAY. MY CURIOSITY IS BECAUSE YOU KEEP -- YOU USE THE TERM "SPINAL MANIPULATION," WHICH IS TYPICALLY THE TERM THAT IS USED IN CHIROPRACTIC MANIPULATION. AND IS CONSIDERABLY DIFFERENT FROM OSTEOPATHIC MANIPULATION. AND SO I'M CURIOUS ABOUT THAT. AND ALSO WHEN YOU SPECIFICALLY REFERRED TO FORCE-BASED MANIPULATION, ARE YOU REFERRING TO A THRUST-BASED LIKE A TYPICALLY CHIROPRACTIC APPROACH OR IS IT ANY FORCE SPECIFICALLY LIGHTER, OSTEOPATHIC MANIPULATION USES A COUPLE OF DOZEN OTHER TECHNIQUES AND DOES NOT FOCUS JUST ON THE SPINE, BUT INSTEAD WORKS ON THE HEAD AND THE VISCERA AND EXTREMITIES AND EVERYWHERE ELSE, AND I'M WONDERING IF THE WAY THAT THIS IS BEING WORDED IS EXCLUSIONARY. >> WE DO REFER TO FORCE-BASED MANIPULATIONS TO INCLUDE TOUCH, IT COULD BE PRESSURE TOUCH, IT COULD BE LIGHT TOUCH, COULD BE THRUST, IT COULD BE REFERRED TO AS SPINAL MANIPULATIONS, ANYTHING THAT RELATES TO EXTERNAL FORCE. YOU BRING EXACTLY THE POINT THAT WE'RE TRYING TO WORK WITH AT THE WORKSHOP, AND MOVING FORWARD WITH THIS INITIATIVE, WHICH IS THE LACK OF COMMON TERMINOLOGY IN DIFFERENT PROFESSIONS MIGHT USE DIFFERENT TERMINOLOGY FOR THE SAME ACTUAL MANIPULATION. SO THIS IS COMPONENT WE HOPE TO BRIDGE HERE. >> DR. EVANS AND DR. -- >> I'M SORRY, CAN I MAKE ONE QUICK COMMENT? >> PLEASE GO AHEAD. >> I WOULD RESPECTFULLY DISAGREE IT'S THE SAME ACTION. IT'S FROM HAVING SEEN A CHIROPRACTOR FOR YEARS BEFORE I WENT TO OSTEOPATHIC MEDICAL SCHOOL, AND FROM HAVING EXTENSIVE CONVERSATIONS OVER ABOUT THE LAST TWO DECADES WITH ALL DUE RESPECT TO EVERYBODY THERE, PARTAP INCLUDED, IT'S NOT THE SAME. THAT'S ONE OF THE FOUNDATIONAL MISINTERPRETATIONS OR MISUNDERSTANDINGS, WE CANNOT LOCK TOGETHER MANUAL THERAPIES AND EXPECT THEY ARE THE SAME THING. >> WE'RE NOT LUMPING. WE'RE INTERESTED IN DIFFERENCES AS WELL AS SIMILARITIES. THE GOAL IS JUST TO GET CLINICIANS AND RESEARCHERS TOGETHER TO TALK ABOUT THIS. SO THIS IS -- I MEAN THE POINTS YOU'RE RAISING ARE EXACTLY THE KIND OF DISCUSSIONS WE'RE HOPING ARE GOING TO HAPPEN AT THESE NETWORKS. >> EXCELLENT. CAN WE MAKE SURE THAT THERE'S SOME OSTEOPATHIC REPRESENTATION AT THEM? >> ABSOLUTELY. >> I LOVE THIS CONCEPT. I LOVE THE MODEL. THE FACT THAT THE PSYCHOSOCIAL IS IN THERE, THIS IS REALLY GOING TO LEAD US TO THAT WHOLE PERSON, LIKE WHAT DO CHIROPRACTICS, OSTEOPATHS, PHYSICAL THERAPISTS, AND PUNCTURISTS, ANYBODY DELIVERING THESE TYPES OF TREATMENTS, THERE'S SO MUCH MORE THAN JUST THAT, MANIPULATION, SO I FIND THIS VERY EXCITING. >> I DIDN'T SEE ANYTHING EXCLUSIONARY, IF ANYBODY WANTS TO LOOK AND STUDY IT, AND I THINK IT'S ENCOURAGING ACROSS -- YOU KNOW, ACROSS DISCIPLINARY APPROACHES TO IT. I DIDN'T SEE ANYTHING EXCLUSIONARY AT ALL. >> OKAY. I'LL GO AHEAD AND ENTERTAIN A MOTION FOR APPROVAL OF THIS CONCEPT. SO MOVED. SECONDED? SECONDED. ANY FURTHER DISCUSSION ON THE MOTION? WE'LL GO AHEAD AND TAKE A VOTE. ALL THOSE IN FAVOR OF APPROVING THIS CONCEPT PLEASE INDICATE BY RAISING YOUR HAND. WE'LL GET A COUNT. PUT YOUR HANDS DOWN. AND THEN ON THE PHONE, I KEEP SAYING THE PHONE, ON THE VERY SOPHISTICATED VIDEO CONFERENCE, DR. HENSEL? DR. HENSEL? >> CAN YOU HEAR ME? >> NOW WE CAN. >> OKAY. SORRY. IT'S CLOSE ENOUGH TO THE PHONE. I APPROVE AND WOULD WELCOME THE OPPORTUNITY TO BE INVOLVED IN FURTHER DISCUSSIONS. >> THANK YOU, DR. HENSEL. DR. TIMERMAN? >> I APPROVE. >> DR. YAY? >> I APPROVE. I THINK IT'S VERY IMPORTANT TO GET EVERYBODY ON THE SAME PAGE AND AT THE TABLE TOGETHER. THANK YOU. >> ANYONE VOTING NOT TO APPROVE THIS? WE'LL RECORD THAT THEN AS UNANIMOUS. JUST A BRIEF LAST BUSINESS BEFORE WE BREAK FOR LUNCH HERE MOMENTARILY. I WANT TO LET EVERYONE KNOW THAT THERE IS A -- FOR COUNCIL MEMBERS, TO MY RIGHT, THOSE AT THE VIDEO CONFERENCE DON'T CARE BUT EVERYONE ELSE TO MY RIGHT THERE'S A BREAK ROOM, IF YOU WOULD LIKE TO GO AND GET LUNCH IN THE CAFETERIA WHICH IS RUN LEVEL UP FROM US, AND BRING IT BACK TO THAT BREAK ROOM, OR IF YOU WANT TO GO IN THERE AND HANG OUT, THAT'S FINE. THE CAFETERIA IS ON THE FIRST FLOOR IF YOU FOLLOW YOUR NOSE AND YOUR EYES, YOU'LL FIND IT. IT'S UP THERE. KEEP WANDERING ONE WAY YOU'LL GO OUTSIDE, THE OTHER WAY WILL TAKE YOU TO THE CAFETERIA. WE'LL PLAN TO MEET BACK HERE AT 1:00 TO CONTINUE THE OPEN SESSION. DR. LANGEVIN? >> BON APPETIT. >> SO, WE HAVE A REALLY COMPETING SYMPOSIUM THAT IS GOING TO -- WAS SCHEDULED TO BE FIRST UP BUT WE HAVE SOME IMPORTANT NEWS THAT DR. FISHBEIN IS GOING TO SHARE BECAUSE HER FLIGHT GOT CANCELED AND SHE HAS TO MAKE NEW ARRANGEMENTS, I WANTED TO MAKE SURE SHE COULD GIVE THIS TWO TO THREE MINUTES OF ANNOUNCEMENT ABOUT SOME THINGS SHE'S BEEN WORKING ON. >> THANK YOU, PARTAP. QUICKLY, WHEN I HEARD THAT RESEARCH WAS ABLE TO CHANGE CMS REGULATIONS ABOUT ADDING ACUPUNCTURE TO BEING A COVERED SERVICE, I WONDERED IF PEOPLE REALIZE HOW AMAZING THAT IS. I MEAN, IT'S VERY DIFFICULT TO MOVE CMS, YOU HAVE TO HAVE STRONG RESEARCH. SO IT WAS REALLY A GREAT COUP AND GOT ME EXCITED. I WANTED TO TELL YOU QUICKLY, WE'VE BEEN WORKING ACTUALLY WITH CMS, HAVING GREAT STRIDES ADDING FAMILY INTERVENTIONS TO THEIR COVERAGE, AND WE'VE HAD A LOT OF SUCCESS. THERE'S STILL A NUMBER OF RESTRICTIONS HAVING TO DO WITH THAT, WE'RE STILL WORKING WITH THEM, BUT THERE'S A LOT OF POTENTIAL FOR RESEARCH, WHEN THERE'S A FIELD CONSENSUS. I HAVE TO REALLY EMPHASIZE THAT. THERE HAS TO BE A GOOD BODY OF EVIDENCE THAT'S CONVINCING, AND CONSENSUAL IN THE FIELD, FOR US TO GO TO CONGRESS WITH THIS SORT OF INFORMATION. BUT WE DO THIS ON A REGULAR BASIS WHEN THERE IS A FIELD CONSENSUS, AND WE'RE BRINGING PREVENTION SCIENCE IN PARTICULAR TO CONGRESS. I HAVE A NATIONAL COALITION THAT I RUN. OUR MANDATE, SELF IMPOSED MANDATE, TO BRING SCIENCE TO POLICYMAKERS IN WAYS THAT BE LEGISLATIVELY RELEVANT, TO IDENTIFY THE SCIENCE AND WE DO BRIEFINGS AND WE HAVE DIRECT CONNECTIONS WITH THEM. WE'VE ACTUALLY RECENTLY LAUNCHED OUR OWN CONGRESSIONAL CAUCUS THAT WE INVITED LEGISLATIVE MEMBERS INTO SO THAT WE HAVE A HOME ON THE HILL. SO THAT WE CAN HAVE A DIRECT ROUTE TO PROVIDE THEM WITH INFORMATION AGAIN THAT'S LEGISLATIVELY RELEVANT. WE DO NOT LOBBY. REALLY QUICKLY, THE MOST RECENT BRIEFING WE RAN WAS IN THIS NOVEMBER, WE HAD A BRIEFING ON THE VERY SIGNIFICANT POLICY IMPLICATIONS OF THE DIFFERENCE BETWEEN ADDICTION AND DEPENDENCE, IT OCCURRED TO ME WHEN SOMEONE I KNEW COMMITTED SUICIDE AFTER HAVING OPIOIDS REMOVED WITHOUT -- BEING TOLD YOU HAVE THREE WEEKS TO WITHDRAW. SHE WAS A MOTHER. SHE WAS JUST LIKE YOU AND I. SHE HAD A DISABLED SON THAT SHE LIFTED FOR 28 YEARS AND HAD SEVERE BACK PROBLEMS. AND SHE USED OPIOIDS TO FUNCTION. SHE WAS DEPENDENT AND NOT ADDICTED. AND, YOU KNOW, COMMON JOE INCLUDING POLICYMAKERS DON'T UNDERSTAND THAT DISTINCTION, AND IT'S HUGELY IMPORTANT FOR US TO UNDERSTAND THAT PEOPLE WHO ARE, YOU KNOW, DEPENDENT ON OPIOIDS NEED ALTERNATIVES. THEY NEED TO BE WITHDRAWN IN A CERTAIN WAY. THEY NEED ALTERNATIVES TO HELP THEM THROUGH WITHDRAWAL. AND TO SUBSTITUTE FOR THAT. BUT WE ALSO NEED TO START THINKING OBVIOUSLY ABOUT PREVENTION IN TERMS OF, YOU KNOW, PREVENTING PEOPLE FROM BECOMING DEPENDENT. BUT PEOPLE WHO ARE DEPENDENT ARE NOT ON THE STREET, YOU KNOW, COMMITTING CRIMES TO SEEK HEROIN UNLESS THEIR OPIOIDS ARE WITHDRAWN AND THEN PEOPLE WILL DO JUST ABOUT ANYTHING TO RELIEVE THEIR PAIN. WE DID A CONGRESSIONAL BRIEFING ON THIS TOPIC, NORA VOLKOW, THE DIRECTOR OF NIDA WAS OUR SPEAKER, A PAIN MEDICATION FROM HERSHEY WHO TREATS PEOPLE END OF LIFE HAVING PAIN MEDICATIONS WITHDRAWN. THEY ARE DYING. THEY HAVE MONTHS TO LIVE. YOU CAN'T IMAGINE HOW WIDE RANGING THESE BLANKET POLICIES THAT HAVE BEEN INDISCRIMINATELY ROLLED OUT, HOW WIDESPREAD THE IMPLICATIONS HAVE BEEN FOR PEOPLE WHO ARE PAIN PATIENTS, AND THERE ARE LITERALLY PROBABLY HUNDREDS OF THOUSANDS OF PAIN PATIENTS WHO ARE STARTING TO ORGANIZE AROUND THIS THEME. WE ALSO HAVE AN OPIOID ADDICTION SPECIALIST, AND A PAIN PATIENT WHO HAPPENED TO BE A POSTDOC, AND A PREVENTION SCIENTIST. IT WAS REALLY A TREMENDOUS BRIEFING. IT'S ON OUR WEBSITE IF YOU WANT TO WATCH IT. I I WANTED TO MENTION IT. IT'S A VEHICLE. WHEN WE HAVE COMPELLING RESEARCH LET'S HAVE IMPACT. WE DON'T LOBBY; WE EDUCATE AND INFORM. JUST SO YOU KNOW ABOUT THAT. >> THANK YOU, DR. FISHMAN. >> CAN I JUST ADD ONE THING? IT BEGS THIS -- I THINK THERE'S NO FIELD THAT BETTER DEMONSTRATES THE FACT THAT FACTS DO NOT SELF AGGREGATE INTO DECISIONS. IF FACTS HAD SELF AGGREGATED INTO DECISIONS THIS WOULD HAVE HAPPENED A LONG TIME AGO. WHAT REALLY MADE THE ACUPUNCTURE CMS THING WORK WAS LEADERSHIP. I THINK WE OWE IT TO SERRIE LING AND OTHERS WHO MADE IT HAPPEN. WE CAN'T JUST SPONSOR RESEARCH. WE HAVE TO LEAD AND ADVOCATE, WHY IT'S SO IMPORTANT TO HAVE SO MANY PEOPLE HERE. >> THANK YOU, DR. SHOEMAKER. THANK YOU, DR. FISHMAN. NOW WE'RE GOING TO START OUR SYMPOSIUM ON CLINICAL TRIALS AN OVERSIGHT. DR. LANGEVIN? >> TAG, YOU'RE IT. YES, THANK YOU FOR COMING TO THIS AFTERNOON'S SESSION. WE'RE GOING TO REVISIT AND EVALUATE PROGRESS ON OUR CLINICAL TRIALS OVERSIGHT. TO PUT THIS IN CONTEXT IN 2017, 2018, NIH LAUNCHED A SERIES OF INITIATIVES TO ENHANCE ACCOUNTABILITY AND TRANSPARENCY FOR CLINICAL RESEARCH, AND THIS AT THE TIME WAS A MULTI-FACET EFFORT TO INCLUDE QUALITY AND CLINICAL TRIALS, FOCUSING ON KEY POINTS ALONG THE RESEARCH CONTINUUM, FROM CONCEPT REVIEW TO FUNDING TO OVERSIGHT, AND MONITORING AND IMPORTANTLY TO RESULTS RECORDING. AND THESE CHANGES ARE AIMED AT ENHANCING NIH'S ABILITY TO ASSESS THE MERITS AND FEASIBILITY OF CLINICAL TRIAL APPLICATIONS, IMPROVE OVERSIGHT AND TRANSPARENCY. IMPORTANTLY, INCREASE THE SHARING OF CLINICAL TRIAL RESULTS, SOMETHING THAT WAS NOT HAPPENING BEFORE POLICIES WERE PUT IN PLACE. WE'RE GRATEFUL TO HAVE DR. MIKE LAUER HERE TO GIVE AN UPDATE AND PROGRESS REVIEW OF NIH POLICY REGARDING CLINICAL TRIAL OVERSIGHT. IN ADDITION, NCCI NCCIH HAS BEEN AT THIS FOR A LONG TIME, DR. EMMELINE EDWARDS AND DR. CATHERINE MEYERS WILL DISCUSS GOALS FOR OVERSIGHT AND CLINICAL RESEARCH AT NCCIH WHICH ALIGNS WITH WHAT'S GOING ON AT THE NIH LEVEL. JUST ON A PERSONAL NOTE, I CAME TO NCCIH IN 2013, AND THE FIRST THING I SORT OF DIVED RIGHT INTO WAS LOOKING AT AND HELPING AND WORKING WITH EMMELINE AND CATHY ON EXAMINING POLICIES AND PROCEDURES, AN ENLIGHTENING -- AS A BASIC SCIENTIST THAT WAS ENLIGHTENING TO ME, AND THAT WAS WOULD HAVE HAD IN DETERMINING RIGOR AND REPRODUCIBILITY OF CLINICAL RESEARCH, WHAT OVERSIGHT REALLY MEANT. THAT WAS A YEAR-LONG PROCESS THAT RESULTED IN 2015 A CHANGE IN HOW WE LOOKED AT AND REVIEWED CLINICAL TRIALS AND THE PROCESSES BY WHICH WE CONDUCTED OVERSIGHT. IT CONTINUES TODAY. IT'S A DYNAMIC PROCESS, WE'RE CONSTANTLY LOOKING TO EVALUATE OUR PROCESS. WE VALUE FEEDBACK FROM MANY DIFFERENT DIRECTIONS. AND WE CONTINUE TO DEFINE THIS PROCESS AND PROVIDE RESOURCES AND TOOLS TO THE COMMUNITY. THE RESEARCH COMMUNITY. BUT THE GOAL OF COURSE IS TO FACILITATE RIGOROUS RESEARCH AND SUPPORTING VERY ROBUST CLINICAL RESEARCH PORTFOLIO. TODAY'S GOAL REALLY IS TO HAVE THAT OPPORTUNITY FOR YOU TO HEAR WHAT WE'RE DOING AT THE NIH LEVEL FROM DR. LAUER, WITHIN THE CENTER, AND HAVE AN OPEN DISCUSSION ABOUT WHAT YOU THINK AND WHERE WE CAN GO FROM HERE. WITH THAT I'LL TURN IT BACK OVER. >> THANK YOU, DAVID. WE WANT THIS TO BE A DIALOGUE, AND I THINK WE WANT PEOPLE TO SEE WHAT IT'S LIKE FROM OTHER PEOPLE'S POINTS OF VIEW, RIGHT? THAT'S HOW GOOD COMMUNICATION STARTS. WE REALIZE THAT THERE HAVE BEEN SOME PAIN POINTS ALONG THE WAY, IN THIS PROCESS. BUT WHAT WE HOPE TO SHOW TO YOU IS THAT WE'VE BEEN LISTENING, WE'VE BEEN ADAPTING OUR POLICIES AND PROCEDURES TO WHAT WE PERCEIVED WERE DIFFICULTIES BOTH WITH SOME -- WE UNDERSTAND THIS IS REGULATION AND OVERSIGHT, IT'S A LOT OF WORK FOR US AND NCCIH, FOR THE INVESTIGATORS, BUT WE THINK IT'S WORK THAT'S IMPORTANT. AND SO WHAT WE WANT TO DO TODAY IS REALLY CONTINUE THIS CONVERSATION AND WANT TO HEAR FROM YOU. WHAT DO YOU THINK ABOUT THIS? AND SO I'D LIKE TO INTRODUCE NOW DR. MIKE LAUER, DEPUTY DIRECTOR FOR EXTRAMURAL RESEARCH, WHERE SERVES ON MATTERS RELATING TO SUBSTANCE, QUALITY, EFFECTIVENESS OF NIH EXTRAMURAL RESEARCH PROGRAM. >> THANK YOU VERY MUCH FOR INVITING ME BACK. I OBSERVE IT WAS ALMOST EXACTLY TWO YEARS AGO THAT I LAST MET WITH YOU. I UNDERSTAND THAT I MET WITH SOME OF YOU THEN, AND SOME OF YOU NOT. I DON'T REMEMBER WHETHER IT WAS WEAR RED DAY. [LAUGHTER] AND I CONFESS I DIDN'T CHECK THE CALENDAR TO SEE. THERE'S A HIGH LIKELIHOOD I WOULD HAVE FORGOTTEN TO DO THAT, AND THERE WAS A TIME IN MY LIFE THAT I WAS AT NHLBI, I'M A CARDIOLOGIST BY BACKGROUND, AND WOULD ROUTINELY FORGET TO WEAR RED. TODAY BY SOME MIRACLE I ACTUALLY PUT ON THE RIGHT TIE. OKAY. YOU HAVE TO KNOW HOW TO TALK TO IT OR SOMETHING? >> UH-UH. >> OKAY. SO, HALF OF THIS IS REVIEW, HALF OF THIS IS NEW. THIS IS HOW I STARTED THE LAST TIME, AND THIS WAS PROBABLY THE STUDY THAT CATALYZED THE EFFORTS TO RETHINK HOW NIH AS AN AGENCY OVERSEES ITS CLINICAL TRIALS. THIS WAS A STUDY OUT OF INVESTIGATORS FROM YALE AS WELL AS NATIONAL LIBRARY OF MEDICINE, AND WHAT THEY DID WAS LOOKED AT TRIALS THAT HAD BEEN -- FUNDED BY NIH AND THAT WERE REGISTERED IN clinicaltrials.gov, THEY USED WHEN THE TRIALS ENDED AND LOOKED TO SEE HOW LONG IT TOOK UNTIL THE MAIN TRIAL RESULTS WERE PUBLISHED. SO THE X-AXIS SHOWS THE TIME FROM STUDY COMPLETIONS, ZERO MEANS STUDY IS OVER, DOESN'T MEAN THE STUDY STARTED. IT'S OVER. WHICH MEANS THEORETICALLY RESULTS COULD BE PUBLISHED THE VERY NEXT DAY, AND THEN THE Y-AXIS IS PERCENT OF STUDIES THAT HAVE BEEN PUBLISHED. SO WHAT YOU SEE HERE IS THAT IF YOU GO TO, SAY, 30 MONTHS, WHICH WOULD BE I GUESS -- ALL RIGHT, ONLY ABOUT 50% OF TRIALS HAD BEEN PUBLISHED AFTER 2 1/2 YEARS. THERE WERE A SUBSTANTIAL NUMBER OF TRIALS THAT EVEN AFTER 100 MONTHS OF FOLLOW-UP HAD NEVER BEEN PUBLISHED AT ALL. SO, THE AUTHORS WROTE THERE ARE MANY NIH-FUNDED TRIALS THAT WERE NOT UNDER A POLICY THAT REQUIRED RESULTS REPORTING. FDAAA, THE FDA AMENDMENTS ACT, REQUIRES REPORTING, SUCH AS TRIALS OF BEHAVIOR INTERVENTIONS AND SURGICAL PROCEDURES. NO POLICIES EXIST TO MAKE SURE THE PUBLIC HAS ACCESS TO RESULTS FROM NIH-FUNDED RESEARCH THAT'S NOT PUBLISHED. ESSENTIALLY, IF THE RESEARCHERS THEMSELVES DON'T PUBLISH THE RESULTS, THE PUBLIC IS OUT OF LUCK. WE HEARD ABOUT THIS, THIS PAPER CAME OUT IN I GUESS -- YEAH, 2012, BEGINNING OF 2012. OUR INITIAL REACTION TO THIS WAS UTTER DISBELIEF. WE COULD NOT BELIEVE ACADEMICS WOULD NOT PUBLISH RESULTS OF THEIR STUDIES. AFTER ALL, A PUBLICATION IS CURRENCY OF ACADEMIA. WE ASSUMED THAT WAS METHODICALLY FLAWED, AND THE PROBLEM WAS THEY DIDN'T COLLECT THEIR DATA PROPERLY. WE DECIDED WE WOULD DO IT RIGHT. WE WOULD LOOK AT CARDIOVASCULAR TRIALS AND IF WE COULDN'T FIND THE PUBLICATION WE WOULD CALL UP THE P.I. AND SURELY IT WAS THAT WE DIDN'T KNOW HOW TO LOOK PAPERS UP AND THEY WOULD SEND US THE PAPERS AND EVERYTHING WOULD BE ABSOLUTELY FINE. AND SO WE DID THAT. WE FOUND 244 CLINICAL TRIALS THAT HAD BEEN FUNDED OVER ABOUT A PERIOD OF 12 -- 10 YEARS OR SO. THEY HAD ALL BEEN COMPLETED. AND WHAT WE FOUND WAS PRETTY CONCERNING. SO THE BOTTOM LINE IS, AND WE DID PUBLISH THESE RESULTS, IN THE NEW ENGLAND JOURNAL, THE BOTTOM LINE IS THAT WE ESSENTIALLY REPLICATED THE FINDINGS. WE FOUND THAT SUBSTANTIAL NUMBER, I THINK MAYBE 45% OF THE TRIALS THAT HAD BEEN FUNDED WERE NOT PUBLISHED WITHIN 2 1/2 YEARS OF COMPLETION. NOW, WE THEN WENT A LITTLE BIT FURTHER AND WE SPLIT THE TRIALS UP INTO THOSE THAT FOCUSED ON HARD CLINICAL ENDPOINTS, AND THOSE THAT DID NOT. SO ON HERE, THIS GRAPH IS SIMILAR TO THE PLOT THAT WE SAW BEFORE, SO THE X-AXIS IS YEARS AFTER THE TRIAL WAS COMPLETED. AND THIS GOES FROM 0 TO 60, SO THAT WOULD BE FIVE YEARS. AND THEN THE Y-AXIS IS THE BEEN PUBLISHED BY THAT POINT IN TIME. AND THE TOP LINE SHOWS THOSE TRIALS THAT HAD CLINICAL ENDPOINTS. WHAT YOU CAN SEE HERE IS THAT AFTER TWO YEARS, ESSENTIALLY ALL THESE TRIALS HAD BEEN PUBLISHED. AND THIS IS WHAT MATCHED OUR GENERAL IMPRESSION, TRIALS PUBLISH. NOT ONLY DO THEY PUBLISH, THEY PUBLISH WITH GREAT FANFARE, WITH PRESS, MEDIA, AND IN VERY PRESTIGIOUS JOURNALS. THE PROBLEM IS THAT THOSE TRIALS THAT FOCUSED ON HARD CLINICAL ENDPOINTS ONLY REPRESENTED 20% OF THE TOTAL PORTFOLIO. SO THERE WERE ABOUT 45 TRIALS THAT FOCUSED ON HARD CLINICAL ENDPOINTS, THERE WERE 199 THAT FOCUSED ON SURROGATE ENDPOINTS AND THE PICTURE THERE WAS QUITE DIFFERENT. THERE, AFTER ABOUT A YEAR, ONLY 10% OF THOSE TRIALS HAD PUBLISHED, AFTER TWO YEARS IT WAS MAYBE 30%, AND SO BECAUSE OF THAT THE OVERALL RATE OF PUBLICATION WAS VERY LOW. SO IN OUR EFFORTS TO REFUTE THE RESULTS OF THE PAPER THAT FOLKS FROM YALE AND NLM HAD PUBLISHED, WE REPLICATED THEIR FINDINGS AND MAYBE WE ALSO CAME UP WITH SOME ADDITIONAL INSIGHTS. WE WROTE IN OUR DISCUSSION A NUMBER OF PARTIES SHARE RESPONSIBILITIES FOR THE STATE OF AFFAIRS, INCLUDING FUNDERS, INVESTIGATORS, ACADEMIC MEDICAL CENTERS, CLINICAL RESEARCH ORGANIZATIONS, AND JOURNALS. NOW, THE NEXT PART OF THIS WOULD BE ACADEMIC MEDICAL CENTERS, AND SO THERE WAS ANOTHER PAPER, I DID SHOW THIS TO YOU, PUBLISHED IN 2016, ALSO FROM THE GROUP AT YALE WHAT THEY DID WAS LOOKED AT ALL CLINICAL TRIALS, NOT JUST THOSE FUNDED BY NIH, BUT ALSO THOSE FUNDED BY INDUSTRY OR FOUNDATIONS OR BY INSTITUTIONS THEMSELVES, AND THEY LOOKED TO SEE WHAT PROPORTION OF THOSE TRIALS HAD THEIR RESULTS REPORTED WITHIN TWO YEARS OF COMPLETION IN ONE WAY OR ANOTHER. EITHER THROUGH A PUBLICATION IN PEER REVIEWED JOURNAL OR BY POSTING OF THE RESULTS IN clinicaltrials.gov. SO THE X-AXIS ARE INSTITUTIONS, AND THE Y-AXIS IS THE PERCENT THAT HAD REPORTED OUT WITHIN TWO YEARS. AND THE WINNER OF THIS COMPETITION, BY THE WAY THE REASON WHY THEY DID THIS STUDY WAS THEY WERE GOING TO IDENTIFY INSTITUTIONS THAT HAD 90% OR 95% OF STUDIES PUBLISHED, AND THEN WHAT THEY WERE GOING TO DO WAS THEY WERE GOING TO GO MEET WITH THEM, THIS IS LIKE MIXED METHODS RESEARCH, THEY WERE GOING TO MEET WITH THEM AND SAY, SO, HOW DO YOU DO IT? BUT THEY DIDN'T QUITE GET TO THAT STAGE BECAUSE THE WINNER WAS THE UNIVERSITY OF MINNESOTA, AND IF ANYBODY IS HERE FROM THE UNIVERSITY OF MINNESOTA, DON'T SAY ANYTHING. [LAUGHTER] TOO LATE NOW. SO, THEY HAD 55%. AND THEN YOU CAN SEE THAT THE VAST MAJORITY WERE AROUND 30 TO 40%. THESE ARE ESSENTIALLY WHO'S WHO OF MAJOR INSTITUTIONS IN THE UNITED STATES. SO THE AUTHORS SAID DESPITE ETHICAL MANDATE AND EXPRESSED VALUES OF ACADEMIC INSTITUTIONS THERE'S POOR PERFORMANCE ACROSS LEADING ACADEMIC MEDICAL CENTERS, THIS IS ONE PROBLEM, LOW RATE OF REPORTING. WE HAD ANOTHER PROBLEM. THIS WAS IDENTIFIED FOR US BY THE GAO, THE GOVERNMENT ACCOUNTABILITY OFFICE, AND THEY DID A STUDY OF HOW WELL NIH AS AN AGENCY FUNCTIONS AS A STEWARD OVER CLINICAL TRIALS. THEY WEREN' TALKING ABOUT INDIVIDUAL INSTITUTES AND CENTERS. THEY WERE TALKING ABOUT THE NIH AS ONE AGENCY. AND THEY NICELY SAID -- LET ME JUST READ THIS. NIH'S O.D., THAT'S THE OFFICE OF DIRECTOR, REVIEWS SOME DATA ON CLINICAL TRIAL ACTIVITY, NIH IS LIMITED IN ABILITY TO MAKE DATA-DRIVEN DECISIONS REGARDING THE USE OF $3 BILLION ANNUAL INVESTMENT IN CLINICAL TRIALS. IT'S A NICE WAY OF SAYING THE OFFICE OF THE DIRECTOR HAS NO CLUE WHAT'S GOING ON. [LAUGHTER] AND SO THEY SAID FIGURE OUT A WAY WHICH YOU COULD FIND OUT WHAT'S GOING ON BECAUSE OTHERWISE HOW CAN YOU POSSIBLY TELL US THAT YOU'RE FUNCTIONS AS EFFECTIVE STEWARD. PART OF THAT IS WHY ON YOUR APPLICATIONS WHEN YOU SUBMIT YOUR APPLICATIONS WE HAVE THAT HUMAN SUBJECTS SECTION, AND WE ASK YOU A BUNCH OF QUESTIONS ON THE HUMAN SUBJECT SECTION, SOME OF THEM ARE STRUCTURED DATA FIELDS AND SOME ARE BOXES. AND WE'RE ANSWERING THE GAO, BECAUSE ALL OF THAT DATA COMES INTO OUR CENTRAL SYSTEM AND WE'VE ACTUALLY BEEN ABLE TO START ANALYZING IT WHICH IS IF YOU WANT TO TALK ABOUT IT, WE CAN TALK ABOUT THAT. OKAY. SO, THOSE ARE TWO OF THE MANY PROBLEMS, BUT ONE IS THAT THE RESULTS DON'T GET REPORTED. SO THAT YOU MIGHT CONSIDER TO BE THE OUTPUT. THE OTHER IS IT DOESN'T -- THAT EVEN CONSIDERING FACT RESULTS DON'T GET REPORTED, WE HERE IN THE OFFICE OF DIRECTOR DON'T EVEN KNOW WHAT RESULTS WE SHOULD BE LOOKING FOR. SO IT WAS A LONG ROAD AND IT DEALT WITH A POTENTIAL POLICY TO REQUIRE REGISTRATION AND REPORTING OF ALL NIH-FUNDED TRIALS. THIS OF COURSE REQUIRED US TO COME UP WITH WHAT A DEFINITION OF A TRIAL ACTUALLY IS. THERE WERE EDITORIALS WRITTEN. THIS ONE BY FRANCIS COLLINS AND KATHY HUDSON, ABOUT HOW NIH WAS NOT HAPPY ABOUT THE STATE OF AFFAIRS, AND SO WE PUT OUT A REQUEST FOR COMMENTS. THIS IS BACK IN 2014. IT WAS OUT FOR A NUMBER OF MONTHS, ON A PROPOSED POLICY THAT WOULD ESSENTIALLY REQUIRE REGISTRATION AND REPORTING FOR ALL NIH-FUNDED CLINICAL TRIALS ACCORDING TO THE DEFINITION THAT HAD BEEN PUT OUT BACK IN 2014. AND AFTER WE WENT THROUGH ALL THOSE COMMENTS, IN SEPTEMBER OF 2016 WE RELEASED THE POLICY. THIS IS THE REPORT. THIS IS THE POLICY REPORT IN THE FEDERAL REGISTER. AND IN THERE WE SAY THAT ALL NIH-FUNDED STUDIES, CLINICAL TRIALS, WILL HAVE TO BE REGISTERED AND REPORTED, AND WE WENT ON TO SAY THAT THERE'S AN ETHICAL OBLIGATION HERE, BECAUSE PEOPLE WHO ARE PARTICIPATING IN CLINICAL TRIALS DO SO WITH THE IMPLICIT UNDERSTANDING THAT THEY ARE GIVING TO SCIENCE. AND GIVING TO SCIENCE MEANS THAT THE RESULTS GET REPORTED OUT. OKAY. THERE WAS QUITE A BIT OF PUBLISHTY ABOUT THIS AT THE TIME IN 2016. FRANCIS COLLINS, KATHY HUDSON AND I POSTED A PIECE IN JAMA, AND CARRIE WOLINETZ WHO I MUST SAY DESERVES A LOT OF THE CREDIT FOR PUTTING THESE POLICIES TOGETHER AND SHEPHERDING THEM THROUGH THE PROCESS AND I WROTE SOME BLOGS, AND WE IN ADDITION TO POSTING IT IN THE FEDERAL REGISTER WE ALSO POSTED IT IN THE GUIDE. NOW, AT THAT TIME WE ACTUALLY ROLLED OUT AND DAVID ALLUDED TO THIS A PANOPLY OF POLICIES. IT WASN'T JUST ONE THING. SO WE WANTED TO MAKE SURE OUR STAFF, THAT NIH STAFF WHO OVERSEE CLINICAL TRIALS KNOW SOMETHING ABOUT CLINICAL TRIALS. I THINK YOU'LL BE VERY IMPRESSED BY WHAT EMMELINE AND KATHY HAVE TO SHOW ABOUT HOW THIS CENTER IS OVERSEEING ITS WORK. SO, PART OF THAT IS MINIMUM, OUR STAFF, ALL OF OUR STAFFS, WHO ARE INVOLVED IN THE OVERSIGHT OF CLINICAL TRIALS TAKE GOOD CLINICAL PRACTICE TRAINING AND WE ALSO WOULD REQUIRE THAT OF EXTRAMURAL INVESTIGATORS. ANOTHER ISSUE IS THAT WE WANTED TO MAKE SURE THAT TRIALS CAME IN TO SPECIFIC FOAs, SO THAT THAT WAY THEY WOULD BE REVIEWED ACCORDINGLY, DEPENDING UPON THE SPECIFICS OF THE TYPE OF SCIENCE AND SO WE BROKE OUT OUR FOAs INTO THOSE THAT REQUIRE CLINICAL TRIALS, THOSE THAT DO NOT ALLOW CLINICAL TRIALS, AND THOSE WHERE CLINICAL TRIALS ARE OPTIONAL. A NUMBER OF THE I.C.s HAVE ACTUALLY SET UP AS THEIR OWN POLICY ALL THEIR CLINICAL TRIALS MUST COME IN TO AN FOA THAT THEY RUN OUT OF THEIR OWN SHOP. ANOTHER IS THE SINGLE IRB POLICY. NOW, WE KNEW AT THE TIME THE SINGLE IRB POLICY -- THE SINGLE IRB POLICY SAYS IF YOU'RE RUNNING A MULTI-CENTER STUDY, THIS IS ANY HUMAN STUDY, WHERE THE SAME PROTOCOL IS BEING USED IN MULTIPLE DIFFERENT CENTERS, THAT YOU HAVE TO USE ONE SINGLE IRB THAT WOULD BE PRIMARILY RESPONSIBLE FOR IRB-RELATED ISSUES. AND WE ALREADY KNEW THAT THIS WAS COMING AS PART OF THE REVIEWED COMMON RULE. NOW THAT THE REVIEWS THE COMMON RULE IS HERE, AND IS IN EFFECT, THE SINGLE IRB POLICY IS NOW -- THAT'S THE POLICY. THAT'S THE COUNTRY'S POLICY. BUT INITIALLY WE SET IT UP AS AN NIH POLICY, AND SO THAT GOT IMPLEMENTED I BELIEVE IN 2018, IF I REMEMBER THAT RIGHT. A NUMBER OF OUR TRIALS INVOLVE FDA-REGULATED PRODUCTS, SOME DO AND SOME DON'T, BUT WE PUT TOGETHER A PROTOCOL TEMPLATE. IT IS STRICTLY OPTIONAL. SOME INVESTIGATORS USE IT AND LIKE IT. IT'S A NICE WAY OF MAKING SURE THAT NO MAJOR ELEMENTS GET FORGOTTEN. AND BUT IT'S THERE AS A RESOURCE. AND THEN AT THE VERY END, YOU HAVE THE REQUIRED REGISTRATION AND clinicaltrials.gov, WITHIN 21 DAYS OF WHEN THE FIRST PATIENT IS ENROLLED, AND THEN REQUIRED RESULT SUBMISSION TO clinicaltrials.gov WITHIN ONE YEAR OF THE COMPLETION OF THE STUDY. SO THIS IS THE -- YOU COULD CONSIDER THIS THE PANOPLY OF POLICIES. AND THIS SHOWS THE TIMELINES OF WHEN THESE VARIOUS POLICIES CAME INTO PLACE. AND ON THE BOTTOM IS A WAY OF THINKING ABOUT HOW WE THOUGHT ABOUT THE PROBLEMS, WORKING BACKWARDS. SO ONE OF THE PROBLEMS THAT RESULTS WEREN'T BEING REPORTED, OKAY, FOR THAT REQUIRED RESULTS TO BE REPORTED. WE HAVE TO KNOW WHAT RESULTS WE'RE LOOKING FOR. THAT MEANS STUDIES -- TRIALS HAVE TO BE REGISTERED. IN ORDER FOR TRIALS TO BE REGISTERED WE HAVE TO KNOW THEY EXIST. WE HAVE TO KNOW THAT THEY ARE IN OUR SYSTEM. IN ORDER TO KNOW THEY ARE IN OUR SYSTEM THAT MEANS GOING BACK TO GAO, THAT WE HAVE TO COLLECT DATA SO WE KNOW WE ACTUALLY HAVE A CLINICAL TRIAL. AND SO IN A WAY, THESE VARIOUS STEPS THAT WE'VE TAKEN ABOVE IN PART ADDRESS THE VARIOUS PROBLEMS THAT HAD BEEN BROUGHT TO OUR ATTENTION. OKAY. WE HAVE A WEBSITE. I SHOWED YOU BEFORE. IT KEEPS GETTING UPDATED WHERE YOU CAN -- THERE ARE TOOLS AND THERE'S CASE STUDIES AND THERE ARE LINKS TO VARIOUS SPECIFIC RESOURCES, AND SPECIFIC POLICIES. ONE SPECIFIC AREA WHICH I'M SURE YOU ALL KNOW ABOUT THAT HAS ATTRACTED A LOT OF ATTENTION ARE STUDIES THAT ARE CLINICAL TRIALS IN THE SENSE YOU'RE DOING AN EXPERIMENT ON PEOPLE, YOU'RE DOING SOMETHING TO A PERSON AND THEN YOU'RE TRYING TO SEE HOW THAT AFFECTS AN OUTCOME, BUT YOU'RE DOING IT FOR THE PURPOSES OF STUDYING HUMAN BIOLOGY OR STUDYING HUMAN BEHAVIOR AT A VERY BASIC LEVEL. YOU'RE NOT DOING THIS BECAUSE YOU HAVE AN INTENTION OF A POTENTIAL TREATMENT. SO FOR EXAMPLE YOU'RE NOT TESTING SOME KIND OF PAIN INTERVENTION BECAUSE THAT MAY BE THE TRIAL RESULTS USED IN PRACTICE. SO THESE ARE WHAT WE CAME TO CALL BASIC EXPERIMENTAL STUDIES WITH HUMAN PARTICIPANTS, AND WHAT'S BEEN POINTED OUT TO US, AND WHAT WE RECOGNIZE AS BEING SOMETIMES TRUE IS THAT clinicaltrials.gov IS NOT A GREAT PLATFORM. FOR SOME OF THESE KINDS OF STUDIES. FOR SOME, THEY WORK QUITE WELL. THERE ARE OVER 11,000 BASIC SCIENCE INTERVENTIONAL TRIALS REGISTERED IN clinicaltrials.gov. AND SOME OF THEM ARE ACTUALLY QUITE GOOD, IF YOU ACTUALLY LOOK AT THE REGISTRATION. SOMEONE LIKE ME, WHO IS NOT IMMEDIATELY FAMILIAR WITH THOSE FIELDS, CAN UNDERSTAND WHAT THE EXPERIMENT IS AND IT MAKES A LOT OF SENSE. BUT THERE ARE OTHER TYPES OF BASIC STUDIES WHICH DON'T FIT SO WELL. SO, WE HAVE RELAXED A REQUIREMENT FOR REGISTRATION AND REPORTING FOR BASIC EXPERIMENTAL STUDIES WITH HUMAN PARTICIPANTS IN THE SENSE THAT WE DO NOT REQUIRE THAT REGISTRATION AND REPORTING OCCUR IN clinicaltrials.gov. SO WE ALLOW INVESTIGATORS TO USE ALTERNATIVE PLATFORMS. WE KNOW THERE ARE ALTERNATIVE PLATFORMS OUT THERE, SOME OF THEM ARE QUITE GOOD. AND THAT WE DO. AND IN THE MEANTIME, THIS IS PRIMARILY BEING ORCHESTRATESSED OUT OF OSP, OFFICE OF SCIENCE POLICY, AS WELL AS NLM, THERE IS AN ONGOING ENGAGEMENT TO HELP FIGURE OUT HOW BEST THE GOVERNMENT CAN COLLECT THE DATA THAT IT NEEDS, VIS-A-VIS REGISTRATION AND REPORTING, WHILE ALSO PROPERLY MEETING THE NEEDS OF THE SCIENCE. THAT'S ONGOING, AND I'M ONLY PERIPHERALLY INVOLVED. THEY GIVE ME UPDATES EVERY SO OFTEN, SOUNDS LIKE THERE'S A LOT OF ACTIVITY GOING ON. OKAY. THIS IS A SINGLE IRB POLICY. WE KEPT DELAYING WHEN THAT WAS GOING TO BE IMPLEMENTED BECAUSE OF IMPLEMENTATION CONCERNS BUT WE DID THEN IMPLEMENT IT. AND NOW SINGLE IRB, THIS SINGLE IRB POLICY IS COMMON RULE. AND SO THIS IS CONTINUING TO EVOLVE. NOW, THERE ARE EXCEPTIONS. THERE ARE CERTAIN SITUATIONS WHERE WE HAVE GRANTED EXCEPTIONS THAT SINGLE IRB IS NOT REQUIRED BUT FOR THE MOST PART FOR THE VAST MAJORITY OF MULTI-CENTER HUMAN STUDIES SINGLE IRB POLICY APPLIES. SO, THIS WAS THE FINAL SLIDE I SHOWED TWO YEARS AGO. TWO HEADLINES. ONE THAT HAD COME OUT AROUND THAT TIME, ONE HEADLINE SAID A SURPRISING AMOUNT OF MEDICAL RESEARCH ISN'T MADE PUBLIC, THAT'S DANGEROUS. AND THEN ANOTHER HEADLINE SAID HHS AND NIH TAKE STEPS TO ENHANCE TRANSPARENCY OF CLINICAL TRIAL RESULTS. THIS IS AN ONGOING PROCESS. WE'RE FAR FROM DONE. BUT WE ARE ROLLING OUT THE POLICIES AND I HOPE THIS WAS INTERESTING AND USEFUL. IT PRESENTS HOW WE'RE LOOKING AT THIS FROM A TRANS-NIH POINT OF VIEW. I THINK THE REST OF THE SYMPOSIUM WILL FOCUS ON THE WORK YOU'VE BEEN DOING WITHIN YOUR CENTER. THANK YOU. >> THANK YOU SO MUCH, MICHAEL. >> ANY YES, SIR -- QUESTIONS FOR DR. LOWRY. >> WOULD YOU KNOW ABOUT NULL RESULTS. >> GREAT QUESTION. IS ONE OF THE REASONS WHY TRIALS ARE NOT GETTING PUBLISHED OR BEING PUBLISHED MORE SLOWLY BECAUSE OF NEGATIVE FINDINGS. SO THERE IS A LITERATURE ON THIS, IN GENERAL STUDIES WITH NEGATIVE FINDINGS ARE LESS LIKELY TO GET PUBLISHED OR PUBLISHED OVER A LONGER PERIOD OF TIME. IN OUR COHORT OF 244 TRIALS, WE DID NOT ACTUALLY SEE THAT. WE LOOKED AT THIS. NOW, THIS WAS NOT A TRIVIAL EXERCISE. STUDIES WHERE RESULTS WERE PUBLISHED WE COULD LOOK AT THE PAPER AND MAKE A JUDGMENT WHETHER OR NOT HYPOTHESIS WAS MET OR NOT. FOR THE STUDIES NOT PUBLISHED, WE HAD TO TRY TO FIGURE OUT WHAT THE RESULTS WERE. SO YOU MIGHT SAY, WELL, THAT SHOULDN'T BE HARD. TAKE A LOOK AT THE PROGRESS REPORTS OR TAKE A LOOK AT THE FINAL REPORTS. SO IN SOME CASES THAT ACTUALLY WORKED AND WE COULD LOOK AT FINAL REPORT AND IN SOME CASES WE LOOKED AT THE FINAL REPORT AND HAD ABSOLUTELY NO CLUE WHAT HAD HAPPENED. FOR THOSE CASES WHERE WE DIDN'T KNOW, WE THEN ACTUALLY CONTACTED THE P.I.s PERSONALLY. FIRST WAS MY COLLEAGUES, AND THEN FOR SOME OF THEM THEY HEARD NO RESPONSE. AT THAT POINT I SENT OUT E-MAILS, I SENT OUT AN E-MAIL SAYING NIH DIVISION DIRECTOR REQUESTS YOUR IMMEDIATE RESPONSE. THAT WORKED. [LAUGHTER] THE QUESTIONS I ASKED WERE PRETTY SIMPLE, WHICH WAS DID YOUR PRIMARY ENDPOINT -- WAS YOUR PRIMARY ENDPOINT MET, YES OR NO. SO WHAT WE WERE ABLE -- BY THE WAY, FOR 11 OF THE STUDIES OUT OF 244 STUDIES, THEY WERE NOT ABLE TO TELL US. THEY SAID THEY NEVER ANALYZED THEIR RESULTS. WHICH IS KIND OF STUNNING. SO, OH, ONE OF RESPONSES WAS FROM A LAWYER. [LAUGHTER] HE WAS VERY UPSET. AND HE SAID, NOBODY EVER TOLD US WE HAD TO PUBLISH THE RESULTS OF OUR STUDY. SO I SAID, IT'S OKAY, WE'RE NOT THE GOON SQUAD. WE'RE JUST DOING OUR OWN STUDY. SO ... [LAUGHTER] AND WE WILL PUBLISH IT. [LAUGHTER] SO WE DIDN'T. WE ACTUALLY DID NOT FIND THAT THERE WAS. SO LATER ON WE WENT INTO A LITTLE BIT MORE DEPTH TO SEE IF WE COULD FIGURE OUT PREDICTORS OF MORE RAPID -- ONE PREDICTOR WE IDENTIFIED IN THE ORIGINAL PAPER WAS FOCUSED ON HARD CLINICAL ENDPOINT. SO THOSE PUBLISHED VERY QUICKLY. WE THEN DID A SUBSEQUENT STUDY WHICH WE HAD ONE OF OUR COLLEAGUES WHO WAS NOT AWARE OF PUBLICATION HISTORY OF THE STUDIES, WE HAD HER READ THROUGH EACH OF THE PAPERS. THESE WERE PAPERS THAT WERE ACTUALLY PUBLISHED. THEN USING A VALIDATED SCALE, SORRY, I DON'T REMEMBER WHICH ONE IT WAS, BUT USING A VALIDATED SCALE WE HAD TO RATE EACH OF THE STUDIES FOR THEIR METHODOLOGICAL QUALITY. AND WHAT WE FOUND WAS THAT THAT WAS A VERY STRONG PREDICTOR OF THE RAPIDITY OF PUBLICATION. THOSE STUDIES THAT WERE OF HIGH METHODOLOGICAL QUALITY PUBLISHED VERY QUICKL, IRRESPECTIVE OF WHAT THE RESULT WAS. THAT WAS INTERESTING BECAUSE IT POINTED OUT THESE WERE ALL ITEMS THAT COULD BE ASSESSED AT THE TIME OF INITIAL PROPOSAL. SO, FOR EXAMPLE, WAS THE RANDOMIZATION PROPERLY DESCRIBED, IS THERE -- WHEN APPROPRIATE, IS THERE APPROPRIATE BLINDING OF PEOPLE WHO ARE MEASURING OUTCOMES? SO THAT ALSO GAVE US MORE IMPETUS FOR MAKING SURE FOAs WERE MORE SPECIFIC TO CLINICAL TRIALS AND THAT THE FORMS TO A BETTER DEGREE THAN BEFORE WOULD CAPTURE THAT KIND OF INFORMATION. >> YEAH, OKAY. THANK YOU, MIKE. THAT WAS A PERFECT SEGUE ACTUALLY INTO THE NEXT PART OF THE SYMPOSIUM. I THINK FOR MANY YEARS EVEN BEFORE THE NIH POLICY NCCIH HAS BEEN SERIOUS ABOUT OVERSIGHT OF CLINICAL RESEARCH FOR THE REASONS DR. LAUER JUST POINTED OUT. IT'S A JOINT EFFORT BETWEEN DIVISION OF EXTRAMURAL RESEARCH AND OFFICE OF CLINICAL REGULATORY AFFAIRS. BECAUSE IT'S A TIGHTLY WOVEN PROCESS BETWEEN THE TWO, THE DIVISION AND THE OFFICE, THAT EMMELINE AND KATHY WILL TAG TEAM THIS PRESENTATION AND I THINK EMMELINE WILL START AND KATHY WILL CONTINUE ON WITH ADDITIONAL INFORMATION. I'LL TURN IT OVER TO THEM. >> THE REAL COLLABORATION THAT EXISTS BETWEEN THE DIVISION OF EXTRAMURAL RESEARCH AND OFFICE OF CLINICAL AND REGULATORY AFFAIRS, WE'RE GOING TO TRY TO BE AS ENGAGING AS POSSIBLE AND DOING THIS TAG TEAM, SO OUR FIRST TOOK IN GENERAL ABOUT WHAT'S IN OUR CLINICAL PORTFOLIO AND THE GOALS AND PRINCIPLES FOR OVERSIGHT. CATHY WILL TAKE OVER AND GO INTO MORE DETAIL WHAT CONSIDERATIONS WE USE WHEN WE ESTABLISH THE OVERSIGHT LEVELS FOR THE STUDIES THAT WE'RE OVERSEEING. AND THEN WE'LL TALK ABOUT WHAT'S CURRENTLY OUR, YOU KNOW, POLICY FOR 2020. WE'LL TAKE A BREAK, THAT WILL ALLOW YOU TO POSE QUESTIONS AND HAVE A DISCUSSION ON THE FIRST PART OF THE TALK. THEN WE'LL COME BACK AND ACTUALLY DIVE INTO MORE OF THE PROCESS, HOW DO WE ACTUALLY DO IT, THE PEOPLE THAT ARE RESPONSIBLE, WHAT ARE WE TRYING TO ACCOMPLISH IN TERMS OF COLLABORATION BETWEEN NCCIH AND THE INVESTIGATIVE TEAM. SO LET'S JUST BEGIN. SOME OF YOU MIGHT REMEMBER THAT SLIDE, WHEN WE HAVE OUR PATIENTS FOR COUNCIL MEMBER AND WANT TO EMPHASIZE SOME OF THE UNIQUE ASPECT OF NCCIH WE USUALLY IN THE CONTEXT OF CLINICAL RESEARCH, WE COMPARE WHAT WE HAVE IN OUR CLINICAL RESEARCH SUPPORT PORTFOLIO FOR NCCIH AS COMPARED TO THE NIH. WE'VE AVERAGED OVER THE YEARS ABOUT 60% OF OUR EXTRAMURAL RESEARCH IS FOCUSED ON CLINICAL RESEARCH, AS COMPARED TO 40% FOR OUR BASIC RESEARCH PORTFOLIO. IT'S THE REVERSE AT THE NIH IN GENERAL, WHERE THE MAJORITY OF THE INSTITUTES, THEIR PORTFOLIO IS ACTUALLY 60% BASIC, VERSUS 40% CLINICAL. SO RIGHT THERE WE HAVE THE DISTINCTION THAT ACTUALLY SUPPORTS OUR STRONG INTEREST AND DEDICATION TO OUR CLINICAL RESEARCH PORTFOLIO. SO WHEN WE LOOK AT THE PORTFOLIO OVER THE NUMBER OF YEARS, FOR THE PURPOSE OF THAT TALK WE REALLY HAVE CATEGORIZED, PUT THINGS IN THREE BUCKETS. OUR MIND AND BODY THERAPIES, NATURAL PRODUCTS, AND OUR OUTCOMES AND EFFECTIVENESS STUDIES. THE POINTS I WANT TO MAKE HERE, WE HAVE A VERY DIVERSE AND ROBUST PORTFOLIO. WE HAVE MANY DIFFERENT STUDY DESIGNS, MANY DIFFERENT GRANT MECHANISMS, THAT HAVE EXPANDED OVER TIME. IN FACT, IT'S A GOOD NEWS STORY. FROM THE TIME I'VE COME TO NCCIH TO NOW I'M SEEN A NICE PROGRESSION, NOT ONLY IN THE MATURITY OF THE PORTFOLIO BUT ALSO MATURITY OF THE INVESTIGATORS IN THE INSTITUTION THAT WE ACTUALLY CURRENTLY ARE FUNDING. THIS IS ANOTHER REPRESENTATION OF OUR -- OF THE WAY WE CATEGORIZE. THIS IS EXACTLY REPRESENTATION THAT THE PIECHART THE SHOW YOU WHERE WE TOOK IN TWO TIME POINTS, 2012 AND 2019, AND ESSENTIALLY OUR CLINICAL RESEARCH REALLY STAYS AROUND THE 60% MARK. OUR MIND AND BODY PORTFOLIO HAS ALWAYS BEEN A LITTLE MORE ROBUST. BUT WE ALSO HAVE, YOU KNOW, SOME OF THOSE, YOU KNOW, BAR GRAPHS INCLUDES GRANTS THAT ARE REPRESENTED IN MORE THAN ONE CATEGORY BECAUSE SOME GRANTS COULD BE MIND AND BODY AND ALSO EFFECTIVENESS RESEARCH, OR MIND AND BODY AND NATURAL PRODUCTS; SO HAVING THIS VERY ROBUST AND DIVERSE PORTFOLIO, WE HAVE SOME PRINCIPLE THAT HELPS US WHEN WE THINK ABOUT THE OVERSIGHT OF THAT PORTFOLIO. ONE OF THE PRINCIPLES IS REALLY WE WANT TO MINIMIZE RISK TO THE PARTICIPANTS. BUT IN THE CONCEPT OF RISK, I ALSO WANT TO POINT OUT THAT NOT ONLY IS RISK TO PARTICIPANTS, WE ALSO NEED TO THINK ABOUT RISK TO NCCIH AND RISK TO THE INSTITUTION, WHERE THE STUDY IS BEING CONDUCTED. THE SECOND PRINCIPLE IS REALLY -- YOU ALL KNOW THAT OUR BUDGET IS NOT AS LARGE AS WE WOULD LIKE IT TO BE, SO WE REALLY WANT TO MAXIMIZE THE SUCCESS OF THOSE STUDIES. SO WE WANT TO MAXIMIZE SCIENTIFIC POTENTIAL AND OF COURSE THE IMPACT OF THE WORK WE'RE FUNDING. AND THE THIRD PRINCIPLE IS THAT WE WANT TO MAXIMIZE PRODUCTIVITY AND RELEVANCE TO OUR NCCIH MISSION AND NCCIH PROGRAM. NOW, FOR NCCIH, IT'S EVEN MORE IMPORTANT THAT WE STAY TRUE TO THOSE PRINCIPLES BECAUSE A LOT OF THE INTERVENTIONS THAT WE FUND ARE USED WIDELY BY THE PUBLIC, SOMETIMES WITH VERY LITTLE EVIDENCE OF UNDERSTANDING OF HOW THEY WORK AND ALSO SAFETY. I ALSO WANTED TO HIGHLIGHT THAT WE HAD A NUMBER OF COMMON LIMITATIONS TO THE TRIALS THAT WERE IN THE EARLY STAGE OF OUR NCCIH CLINICAL PORTFOLIO. MANY YEARS BACK, WE HAD A NUMBER OF SINGLE SITE TRIALS, SO IT WAS VERY HARD TO GET THE GENERAL IDEA OF, YOU KNOW, OUTCOME OF THE STUDY, NOT CLEAR WHETHER THE INTERVENTION COULD BE DELIVERED IN OTHER SITES. ALSO, IT'S WORTH POINTING OUT THAT A LOT OF STUDIES -- WE HAD A NUMBER OF FAILED TRIALS, FOR WHATEVER REASON, BUT WE HAD -- WHEN WE HAVE A FAILED TRIAL WE COULD GLEAN SOME GOOD INFORMATION OUT OF THAT. HOWEVER, A LOT OF THE STUDIES DIDN'T -- WERE NOT ACTUALLY CARRIED OUT WITH THE GOOD MECHANISTIC GROUNDING OR THEORETICAL FRAMEWORK, DIFFICULT TO FIGURE OUT WHAT ACTUALLY WENT WRONG. DID WE DELIVER INTERVENTION CORRECTLY? DID WE HAVE, YOU KNOW, DIDN'T GET ENOUGH TREATMENT, WAS IT THE RIGHT DURATION? WAS IT THE RIGHT POPULATION? AND YOU KNOW WE DO HAVE A PRETTY LARGE NATURAL PRODUCT PORTFOLIO. THERE WAS ALSO THE ISSUE, DID WE HAVE THE RIGHT PRODUCT? SO WE REALLY WANTED TO SPEND TIME AND ACTUALLY DEVELOP WAYS THAT WOULD ALLOW OUR INVESTIGATORS TO HAVE THE RIGHT BUILDING BLOCKS THAT THEY NEEDED IN ORDER TO DESIGN THE FOLLOW-UP EFFICACY TRIALS. SO AS MIKE MENTIONED, THERE WAS AN EFFORT TO ACTUALLY DEVELOP THE THEORY OF FUNDING OPPORTUNITY ANNOUNCEMENT THAT WAS VERY SPECIFIC TO SOME AREAS OF RESEARCH. FOR US, WE FUND RESEARCH THAT GOES FROM BASIC AND MECHANISTIC TO TRANSLATIONAL, INTERVENTION, EFFICACY STUDIES, TO PRAGMATIC STUDY AND DISSEMINATION. WE SPENT A GREAT AMOUNT OF TIME TO DEVELOP SPECIFIC FUNDING OPPORTUNITY ANNOUNCEMENT WHICH ALLOWS INVESTIGATORS TO NOW HAVE THE PLACE TO GO, DEPENDING ON THE STAGE OF RESEARCH THAT THEY WERE ACTUALLY, YOU KNOW, INVOLVED WITH. SO, ESSENTIALLY RIGHT NOW IF AN INVESTIGATOR IS DEVELOPING AN INTERVENTION, FOR EXAMPLE, THEY COULD ESSENTIALLY APPLY FOR OUR R34 MECHANISM, WHICH IS STAGE OF RESEARCH WHERE THEY HAVE AN OPPORTUNITY FOR THREE YEARS TO NOT ONLY DEVELOP THE INTERVENTION BUT ALSO REFINE IT AND TRY -- AND HAVE SOME FEASIBILITY DATA, BEFORE THEY COME TO US FOR A FULL FLEDGED EFFICACY STUDY. WE FOUND THIS HELPFUL FOR INVESTIGATORS AND ALSO FOR US BECAUSE WE WANT TO INVEST IN AREAS WHERE WE THINK THAT WE HAVE ENOUGH CONFIDENCE THAT EFFICACY TRIAL WOULD BE WORTH PURSUING. SO I'M GOING TO TURN NOW TO MY COLLEAGUE, CATHY, WHO IS GOING TO DELVE INTO MORE OF THE CONSIDERATIONS FOR THE OVERSIGHT OF THOSE CLINICAL RESEARCH. >> THANK YOU, EMMELINE. I THINK WE'LL BEGIN HERE WHICH REFLECTS BACK A BIT ON SOME OF THE INFORMATION THAT MIKE TOLD US ABOUT. IF WE LOOK AT OVERARCHING GOALS FOR NIH WITH CLINICAL TRIALS OVERSIGHT, AND CERTAINLY THE IMPORTANCE OVER THESE LAST SEVERAL YEARS, FOR ALL OF THE INSTITUTES AND CENTERS OF ENHANCING STEWARDSHIP FOR CLINICAL TRIALS. SO IF WE BEGIN HERE WITH THE -- WITH OUR CLINICAL TRIALS JOURNEY, FROM THE IDEA OF A CLINICAL STUDY THROUGH ALL OF THESE STEPS, ULTIMATELY TO PUBLICATION OF RESULTS, WE SEE THAT THERE ARE A NUMBER OF ASPECTS REALLY CRITICAL TO OUR OVERSIGHT OF THESE STUDIES ALONG THE WAY, AND CLEARLY TO EMPHASIZE THE SUCCESS OF THE CLINICAL TRIALS ENTERPRISE REALLY RELIES ON PUBLIC TRUST IN THE SCIENTIFIC RIGOR, TRANSPARENCY AND OVERSIGHT. NIH IS THE LARGEST FEDERAL FUNDER OF CLINICAL TRIALS IN THE U.S., WITH ITS $3 BILLION ANNUAL INVESTMENT, CLEARLY HAS A LARGE SHARED RESPONSIBILITY WITH INVESTIGATORS IN THEIR INSTITUTIONS. AND SO I SHOW THIS SLIDE TO FOCUS ON A FEW KEY WORDS IN OUR GUIDE BE PRINCIPLES IN TERMS OF RISK, SUCCESS OF OUR FUNDED WORK, AS WELL AS MAXIMIZING THE PRODUCTIVITY AND RELEVANCE OF NCCIH PROGRAMS AS A SMALL CENTER AT THE NIH OF . WE TAKE THIS RESPONSIBILITY OF STEWARDSHIP QUITE SERIOUSLY, BUT ALSO EMPHASIZE THAT THIS IS INDEED A SHARED RESPONSIBILITY, AND WORKING WITH OUR NCCIH SCIENTIFIC STAFF, WORKING WITH OUR INVESTIGATORS AS WE MOVE CLINICAL TRIALS THROUGH OUR PORTFOLIO. I'D LIKE TO PROVIDE A PERSPECTIVE ON LEVELS OF OVERSIGHT WITHIN OUR CLINICAL PORTFOLIO REALLY OVER THE LAST DECADE. EMMELINE AND I BOTH HAVE BEEN AT THE CENTER SINCE I THINK 2009. I THINK THE CENTER HAD A BROAD SPECTRUM OF OVERSIGHT ACTIVITIES AT THEIR DISPOSAL AS THEY LOOKED AT THE CLINICAL PORTFOLIO. WE'VE HAD TWO BROAD CATEGORIES OF OVERSIGHT, ONE IS ROUTINE, THE OTHER ENHANCED. ROUTINE OVERSIGHT INCLUDED PRE-AWARD, NCCIH STAFF DISCUSSIONS AS THEY CLEARED THE IRG AND WE PREPARE FOR COUNCIL, AS WELL AS PRE-AWARD DISCUSSIONS WITH PRINCIPAL INVESTIGATORS. THERE HAS ALWAYS BEEN AN ELEMENT OF PRE-AWARD WRITTEN COMMUNICATION WITH THE P.I. ABOUT PROCESSES WITHIN THE CENTER, AND POST AWARD ACCRUAL INFORMATION THAT'S COLLECTED ONCE A PROJECT IS FUNDED. THE ENHANCED ASPECT OF OVERSIGHT HAS BEEN A SUBSET OF GRANTS WITHIN THE PORTFOLIO THAT HAVE THESE ROUTINE ACTIVITIES BUT ALSO WHERE THE CENTER HAS COLLECTED STUDY DOCUMENTS, POST AWARD, OR COLLECTED STUDY DOCUMENTS AND WE HAVE A SUBSET OF THESE ENHANCED PROJECTS THAT ALSO HAVE ENTERED OUR ON-SITE MONITORING PROGRAM. SO TWO BROAD CATEGORIES, ROUTINE AND ENHANCED, AND WITHIN ENHANCED WE HAVE A SUBSET THAT HAVE ENHANCED WITH ON-SITE MONITORING. AND THAT'S BEEN OUR WORKING STRATEGY OVER THESE LAST MANY YEARS. SO I THINK WE WANTED TO SHOW THE SLIDE AS IT ILLUSTRATES HOW THE CENTER HAS BEEN USING OVER THE LAST SEVERAL YEARS, WE HAVE A GRAPH HERE THAT SHOWS THE PERCENT OF NEW GRANTS, WITH ENHANCED OVERSIGHT, THAT ARE FUNDED IN A GIVEN FISCAL YEAR ON THE X-AXIS AND WE SEE IN THE EARLY YEARS BETWEEN 2011 AND 2014 A HIGH PERCENTAGE OF PORTFOLIO BETWEEN 80 AND 90% OF CLINICAL WORK SUPPORTED IN THE CENTER WAS WITHIN THIS ENHANCED OVERSIGHT CATEGORY. AND CLEARLY THERE IS A CHANGE, EVIDENCED BY THE LARGE BLUE ARROW IN THE MIDDLE THAT SHOWS A SIGNIFICANT SHIFT, IF YOU WILL, IN THE ENHANCED OVERSIGHT PORTFOLIO. AND CERTAINLY DAVID COMMENTED HIS ARRIVAL HERE SOMEWHERE IN 2013, AND THE LATTER PART OF 2014 WE -- >> [OFF MICROPHONE] [LAUGHTER] >> AND OF COURSE OUR TREND, SO WE CERTAINLY HAD A DECREASE THROUGH 2016, AND SINCE 2016 WE HAVE AN ENHANCED OVERSIGHT OF, SAY, 20 TO 30% IN A GIVEN YEAR WHICH DOES VARY. YES? >> [OFF MICROPHONE]. >> OH, THAT'S THE VERY NEXT SLIDE. SO, WHAT HAPPENED? HOW DO WE ACTUALLY COME TO THESE KINDS OF OVERSIGHT DECISIONS? AND HERE WE AGAIN HAVE A NUMBER OF OVERSIGHT CONSIDERATIONS THAT THE CENTER HAS REVIEWED FOR ANY GIVEN PROJECT, AND, AGAIN, IF WE CONSIDER EMMELINE'S EARLIER SLIDE ABOUT THE EVOLUTION IF NOT IN THE CENTER WE HAVE, AGAIN, A DIVERSE PORTFOLIO, A LOT OF DISCIPLINES, CONDITIONS, STUDY DESIGNS, AND A LOT MORE FOAs AND GRANT MECHANISMS. THE THINGS WE THINK ABOUT WITH INDIVIDUAL PROJECTS FOCUS ON THE SIZE AND COMPLEXITY AND NUMBER OF PARTICIPANTS, NUMBER OF SITES, THE PARTICULAR INTERVENTION THAT'S BEING STUDIED, THE TARGET POPULATION, IN PARTICULAR WHETHER THERE'S A FOCUS ON VULNERABLE POPULATIONS AS OUTLINED IN THE FEDERAL REGS, TRIALS OF REGULATED PRODUCTS, THAT'S WITH OVERSIGHT FROM FDA, OR THE DEA, AND INVESTIGATOR EXPERIENCE AS WELL AS APPROPRIATE INSTITUTIONAL INFRASTRUCTURE, FOR CONDUCTING CLINICAL RESEARCH. THOSE ARE THE VARIABLES, NOT NECESSARILY IN A PRIORITIZED OR HIERARCHICAL LIST BUT THEY COME INTO CONSIDERATION ON PRODUCTS. IF WE LOOK AT TRENDS IN PORTFOLIO SINCE 2014, WE SEE THE TREND REFLECTS HOW OVERSIGHT CONSIDERATIONS ARE BEING APPLIED TO CHANGING AND EVOLVING CLINICAL PORTFOLIO, REVIEWED WITH FEEDBACK FROM THE STAFF AND INVESTIGATOR COMMUNITY, AND WE'RE REALLY TARGETING THE OVERSIGHT TASKS FOR LARGER, MORE COMPLICATED STUDIES, WHILE MAINTAINING THESE STEWARDSHIP RESPONSIBILITIES ACROSS THIS CLINICAL PORTFOLIO. WE CLEARLY HAVE LESS ENHANCED OVERSIGHT FOR THE SMALLER MECHANISTIC EXPLORATORY PROJECTS, AS WELL AS WITHIN OUR TRAINING GRANT PORTFOLIO. AND AS EMMELINE COMMENTED EARLIER, WE'VE CERTAINLY SEEN A CHANGE IN THE NUMBER OF EXPERIENCED INVESTIGATORS AS WELL AS INSTITUTIONS THAT HAVE MUCH INFRASTRUCTURE, ADMINISTRATIVE INFRASTRUCTURE, IF YOU WILL, TO SUPPORT CLINICAL TRIALS. AND SO THIS REALLY REFLECTS ONGOING CHANGES IN OUR OVERSIGHT, WHICH I ANTICIPATE WOULD CONTINUE WITHIN THE CENTER, AS OUR PORTFOLIO CHANGES OVER TIME. WE'VE SEEN A LOT OF CHANGE OVER A DECADE. A NUMBER OF STRATEGIC PLANNING EFFORTS UNDERWAY THAT HAVE SORT OF BEEN STEERING WHAT RESEARCH IS SUPPORTED AND NEW INTERESTS WITHIN THE CENTER, AND THAT NECESSARILY FROM THAT HAS -- WE'VE SEEN A NUMBER OF NEW INITIATIVES, AND REALLY QUITE A BROAD SPECTRUM OF MECHANISMS NOW SUPPORTED IN THE CENTER. I THINK AT THIS POINT WE THOUGHT WE WOULD TAKE TIME FOR DISCUSSION AS WE'VE GONE THROUGH THE DESCRIPTION OF GOALS OF OVERSIGHT AND CONSIDERATIONS THAT THE CENTER HAS USED AS WELL AS SORT OF THE STATE OF THE ART, IF YOU WILL, OF OUR OVERSIGHT IN 2020, AND ALLOW PEOPLE TO PERHAPS PROVIDE US WITH SOME INSIGHTS OR QUESTIONS INTO AND DISCUSSION. >> THIS IS GREAT. I THINK BOTH PRESENTATIONS WERE QUITE GOOD, GIVES PERSPECTIVE OF WHERE WE STAND WITHIN THE NIH, WHY WE'RE COMMITTED TO THE OVERSIGHT PROCESS FOR CLINICAL RESEARCH. IT GIVES THE HISTORICAL PERSPECTIVE. WE REALIZE BASICALLY WITH LIMITED BANDWIDTH, OVER TIME, WE'RE FOCUSING MORE ON CLINICAL TRIALS SORT OF FOR THE ENHANCED OVERSIGHT THAT HAS CHARACTERISTICS THAT CATHY AND EMMELINE OUTLINED. THAT FRANKLY IS AN ONGOING DISCUSSION WITHIN THE CENTER, ARE THERE WAYS TO EVEN REFINE THAT, THOSE CRITERIA FURTHER. SO THAT WAS SOMETHING WE APPRECIATED FEEDBACK FROM THE COUNCIL ON OTHER WAYS WE CAN THINK ABOUT CATEGORIZING THESE APPLICATIONS INTO HIGH OR BASIC OVERSIGHT. SO IT'S OPEN FOR YOUR THOUGHTS AND WE WOULD VALUE YOUR -- MANY OF YOU OR SOME OF YOU HAVE GONE THROUGH THIS PROCESS, I THINK. FOR BETTER OR FOR WORSE. BUT I THINK YOU CAN SEE WHY WE'RE COMMITTED TO DOING IT IN THIS SORT OF FASHION BUT WE'RE ALWAYS OPEN FOR FEEDBACK AND WAYS TO IMPROVE UPON PARTICULARLY COMMUNICATION BETWEEN OUR CENTER AND THE INVESTIGATORS, AND THIS IS WHERE YOU COME IN OF COURSE AS THE COUNCIL. SO PLEASE DON'T BE SHY. WE REALLY WANT TO LEARN FROM YOU AND TAKE YOUR FEEDBACK SERIOUSLY TO KEEP ON IMPROVING AND MAKING PROGRESS IN THIS AREA. SO ANY COMMENTS, QUESTIONS? COMPLAINTS? >> WELL, I'M TRYING TO TIE THE TWO PRESENTATIONS TOGETHER FOR A SECOND. I'M JUST CURIOUS, WHERE IN PROGRAMMATIC REVIEW OF AN NCCIH PROPOSAL WOULD LESSONS LEARNED ON THE TRACK RECORD OF PUBLICATION COME IN, ESPECIALLY GIVEN THAT IT MAY NOT BE TAGGED TO THE P.I. IT MAY BE TAGGED TO THE INSTITUTION THEY ARE PART OF OR HAVE BEEN PART OF, I MEAN WITNESS THE LAWYER WHO WROTE, THAT'S NOT NECESSARILY THE P.I. THAT'S THE -- WHERE DOES THAT COME IN? >> WELL, SO WE DO HAVE A -- WE ACTUALLY DO HAVE A PROCESS WHICH WE WOULD DISCUSS SORT OF AS THE PART 2 AND HOW THIS -- HOW THESE CONVERSATIONS AND SORT OF THE CORRALLING OF ALL OF THIS KNOWLEDGE AND INFORMATION ABOUT, YOU KNOW, THE STUDY AND THE COMMUNITY AND THE INVESTIGATORS' EXPERIENCE IS BROUGHT TOGETHER FOR CONVERSATIONS WITHIN THE CENTER, AND CERTAINLY CONVERSATIONS WITH THE INVESTIGATORS. >> SO SPECIFICALLY THEN THE TRACK RECORD OF BOTH PUBLICATION AS WELL AS TIMELINESS OF PUBLICATION COMES INTO THAT DISCUSSION, AND IF -- HOPEFULLY NOT ON THE NEGATIVE SIDE BUT ON THE NEGATIVE SIDE, YOU KNOW, THIS INVESTIGATOR, THIS INSTITUTION, HAS A REPUTATION OF REALLY NOT PUBLISHING, THAT COMES IN AS PART OF IT? >> ABSOLUTELY. AND THAT DURING THE COURSE OF THE CONVERSATION, LET'S SAY THE INVESTIGATOR'S TRACK RECORD AND INSTITUTION'S TRACK RECORD COME INTO PLAY, SO THERE ARE MULTIPLE POINTS, CHECK AND BALANCES POINTS, WHERE, YOU KNOW, IN DISCUSSION OF WHETHER WE'RE GOING TO RECOMMEND SOMETHING FOR FUNDING, THAT HISTORY ACTUALLY PLAYS A VERY GOOD ROLE. >> AND -- >> THAT'S PART OF THE DECISION. >> AT LEAST FOR RESEARCH THAT'S BEEN FUNDED BY THE CENTER OVER TIME, AND AGAIN WE'LL DISCUSS THIS A LITTLE BIT IN THE NEXT PART, THERE'S A VERY LONG HISTORY OF TRACKING RECRUITMENT WITHIN ALL OF THE RESEARCH THAT'S EVER BEEN FUNDED. THE CLINICAL RESEARCH THAT'S BEEN FUNDED BY THE CENTER. AND REALLY TRACKING THE INVESTIGATORS, FOLLOWING THE INVESTIGATORS, AND FOLLOWING ALL OF THE TRIALS TO COMPLETION. SO THAT HISTORICAL INFORMATION DOES INFORM CONVERSATIONS, YOU KNOW, ABOUT THE INVESTIGATOR POOL THAT CONTINUES TO SUBMIT GRANTS TO US SO THAT WE FOLLOW THAT. >> YEAH, I GUESS A FOLLOW-ON, REAL QUICKLY, I IMAGINE THERE'S NOT A NATIONAL DATABASE THAT ALLOWS YOU TO COMPARE ACROSS -- I'M ALWAYS FASCINATED CEOs OF FORTUNE 500 COMPANIES WITH BUST A COMPANY, GET A GOLDEN PARACHUTE, GO TO ANOTHER AND BUST IT. I CAN'T FIGURE OUT WHY SOMEONE DOESN'T COMPARE NOTES. >> PERHAPS ONE OF THE STATED GOALS IS CT.GOV FOR REGISTRATION, AND REPORTING OF ULTIMATELY REPORTING OF ENROLLMENT AND ANALYSIS OF DATA THAT'S ACCUMULATED. >> BACK TO THE TRANSPARENCY ISSUE THAT MIKE COMMENTED ON, WHAT WE'RE TRYING TO DO, SHED LIGHT ON THESE KINDS OF ISSUES SO THAT INFORMATION IS AVAILABLE . >> YEAH, JUST A FEW COMMENTS. I'VE BEEN REALLY APPRECIATIVE OF THE PROCESS WITH NCCIH WE'VE GONE THROUGH WITH TRIALS, SOME HAS BEEN AROUND UG3, UH3 MECHANISM WHICH I KNOW NOT ALL CLINICAL TRIALS ARE OF THAT ILK BUT IT DOES PROVIDE REALLY A FRAMEWORK I THINK FOR THAT KIND OF REVIEW. JUST A COUPLE COMMENTS, AS A RESEARCHER, YOU KNOW, EXTRAMURAL RESEARCHER ON SOME OF THESE AREAS, MAYBE I'M TALKING ABOUT, YOU KNOW, SORT OF NOT WHAT SOME PROCESSES WERE MEANT TO DO BUT SOME UNINTENDED CONSEQUENCES, IF YOU WILL, CATHY, YOU'RE VERY FAMILIAR WITH clinicaltrials.gov AND SOME OF THE PRAGMATIC TRIAL PARAMETERS THAT DON'T FIT EASILY INTO THAT AND SOME CHALLENGES WHICH I KNOW ARE BEING WORKED OUT. THE OTHER PIECE, MAYBE THE HORSE IS COMPLETELY OUT OF THE BARN WITH, THE sIRB PROCESSES ARE REAL CHALLENGING KIND OF THING, AND THEY WORK DIFFERENTLY FOR DIFFERENT TRIALS WITH DIFFERENT INSTITUTIONS, AND IT DOESN'T TAKE AWAY FROM THE MULTI-SITE TRIAL, FOR INDIVIDUAL SITES, REALLY NEEDING TO ADHERE TO STATE REGULATIONS AND ALL SORTS OF OTHER THINGS, AND I FEAR THAT THE OVERSIGHT ACTUALLY IN SOME WAYS CAN BE LESS GOOD WITH sIRB, CERTAINLY FAR LESS EFFICIENT THAN IT USED TO BE BECAUSE THERE'S STILL ALL THE BACK AND FORTH AND THEN THE INSTITUTIONS THAT ARE WILLING TO TAKE ON THAT sIRB ROLE ARE OFTEN EITHER COMMERCIAL ENTERPRISES OR PLACES THAT ARE NOT REAL FAMILIAR WITH THE WORK OR THE INSTITUTIONS AND I THINK THE HIGH LEVEL OF OVERSIGHT IS NOT LOOKING AT THE SPECIFICS. SO, YOU KNOW, IT MAKES SENSE IN PRINCIPLE WHY THAT WAS PUT IN PLACE, AND I JUST THINK MANY OF OUR EXPERIENCES ON THE GROUND WHO ARE NOW DEALING WITH THE CONSEQUENCES OF HOW IT ROLLS OUT IS CHALLENGING. AND THEN THERE WAS ONE OTHER THING I WAS GOING TO SAY. I FORGOT WHAT IT WAS. >> YEAH, I THINK WE CERTAINLY HEARD FROM INVESTIGATORS WITH MULTI-CENTER STUDIES THAT THE SINGLE IRB HAS NOT NECESSARILY REDUCED THE ADMINISTRATIVE BURDEN AND COMPLEXITY OF OVERSIGHT, FOR SOME TASKS, BUT AS WE LOOK AT SOME, EVEN SOME CLINICAL TRIALS IN OUR PORTFOLIO THAT HAVE BETWEEN 50 AND 100 CLINICAL SITES, CLEARLY THERE IS A MARKED REDUCTION IN ADMINISTRATIVE TASKS. THERE IS A GREATER SIMPLICITY FOR LAUNCHING AND CONDUCTING A TRIAL. WHETHER THIS PERHAPS HIGHER LEVEL OF OVERSIGHT FROM SINGLE IRB MAY MISS OR, YOU KNOW, OBVIOUSLY IS A DIFFERENT PERSPECTIVE FROM INCLUDING INDIVIDUAL IRBs, BUT CERTAINLY HAS MADE THESE LARGER, YOU KNOW, WITH MANY, MANY CENTERS MUCH MORE FEASIBLE IN TERMS OF BEING ABLE TO -- >> JUST TO BE CLEAR, I'M TALKING ABOUT TRIALS THAT HAVE FIVE, SIX SITES AT THE MOST, DIFFERENT BALL GAME. I REMEMBER THE OTHER COMMENT I WAS GOING TO MAKE, JUST THAT WITH THE WAY THAT YOU PUT IN TRIALS NOW WITH MORE OF AN EMPHASIS FOR CLINICAL TRIALS OF REALLY THE -- I CAN'T REMEMBER IF IT'S FORM E OR THE SUPPLEMENTAL PIECE, I'VE BEEN STRUCK ABOUT HOW MUCH HETEROGENEITY THERE IS IN THE DIFFERENT RFAs FOR DIFFERENT SPONSORING I.C.s, THAT MIGHT BE FINE. I GUESS I WONDER IF THAT BECAME MORE STANDARD WHETHER IT MIGHT BE MORE USEFUL OVER THE LONG RUN. >> SO, WE'RE NOT YET READY TO ROLL THIS OUT BUT WE'VE BEEN PRODUCING AND INTERACTIVE DASHBOARD, BASED ON DATA THAT COMES IN THROUGH THE HUMAN SUBJECTS SECTION, FORMS E, BY THE WAY THAT DOESN'T ONLY INVOLVE CLINICAL TRIALS, THAT INVOLVES ALL HUMAN STUDIES. ONE ALREADY TANGIBLE OUTPUT OF THAT HAS BEEN OUR ABILITY TO LINK INCLUSION DATA WITH RCDC CATEGORIES. THAT'S OUT. THAT'S SOMETHING WHICH IS NOW PUBLICLY AVAILABLE. THAT WAS ANOTHER GAO REPORT. AND SO -- IN THIS WAY, ONE CAN LOOK AT BOTH THE PUBLIC AS WELL AS WE CAN LOOK AT HOW WELL WE'RE DOING AT INCLUSION ACROSS DIFFERENT CATEGORIES AND DIFFERENT KINDS OF STUDIES. WE'RE ALSO SEEING, FOR EXAMPLE, THIS IS NOT YET OFFICIAL BECAUSE WE'RE STILL WORKING OUT A LOT OF KINKS, BUT WE FIND ABOUT 10% OF OUR CLINICAL TRIALS ARE BASIC SCIENCE STUDIES, WHICH IS ABOUT RIGHT. THE OVERALL PERCENTAGE AMONGST ALL CLINICAL TRIALS MAY BE 3% OR 4%, BUT NIH OF COURSE IS A MORE BASIC SCIENCE STUDY -- BASIC SCIENCE ORIENTED AGENCY. AND THAT NUMBER KIND OF MAKES SENSE. SATS SOMETHING -- THAT'S SOMETHING WE'RE GOING TO DIG INTO MORE DEEPLY. WE STARTING TO WORK WITH THAT. WE'VE DISCOVERED IN PART THROUGH FEEDBACK THAT WE'VE -- FROM INVESTIGATORS THAT SOME OF THE QUESTIONS ARE REPETITIVE, AND PEOPLE HAVE TO PUT IN THE SAME INFORMATION OVER AND OVER AGAIN, AND SO THAT'S SOMETHING WHICH IS HOPEFULLY BEING FIXED, AS WE GO TO FORMS F, FORMS F WILL BE COMING OUT IN MAY. IN FACT ACTUALLY FORM Z, WHEN WE PUT TOGETHER FORM Z A PROBLEM WAS THERE WAS A LOT OF MATERIAL BEING ENTERED IN MORE THAN ONCE, NOT JUST HUMAN SUBJECTS BUT JUST ALL ACROSS THE BOARD. THE PHILOSOPHY WAS WE ONLY WANT TO HAVE INFORMATION NEED TO BE ENTERED IN ONCE. WHAT WE DIDN'T FULLY ACCOMPLISH THAT GOAL BUT HOPEFULLY WE'LL BE CLOSER WITH FORMS F. >> I HAVE A QUESTION ABOUT GETTING FEEDBACK FROM THE SYSTEM, HOPEFULLY SOMEDAY WE'LL HAVE ENOUGH DATA TO BE ABLE TO TELL WHETHER THIS IS MAKING A DIFFERENCE, WHETHE PEOPLE ARE REPORTING, PUBLISHING MORE PAPERS, RECRUITING STUDIES, WHAT'S YOUR ESTIMATE, MIKE, AS TO WHEN WE'LL BE AT A POINT WHEN WE CAN ASSESS THAT? >> POLICY BECAME EFFECTIVE IN JANUARY OF 2017. BUT REALLY BECAME EFFECTIVE IN JANUARY OF 2018 BECAUSE THAT'S WHEN WE PUT TOGETHER THE NEW FORMS BY WHICH WE COULD CAPTURE DATA ON TRIALS. LET'S SAY IT WAS 2017. IF YOU THINK ABOUT THIS, WHEN A TYPICAL RESEARCH GRANT COMES IN, IF IT GETS FUNDED ON THE FIRST GO AROUND, THE AVERAGE LENGTH OF TIME UNTIL IT GETS FUNDED IS ABOUT NINE MONTHS. IF THE -- MOST OF THE TIME IT DOESN'T GET FUNDED THE FIRST TIME AROUND. SO IT MIGHT BE AT LEAST A YEAR TO A YEAR AND A HALF UNTIL THE STUDY ACTUALLY GETS FUNDED. IF WE GO TO, SAY, 2017 WHEN WE FIRST START GETTING APPLICATIONS, THAT MEANS THAT THE ACTUAL STUDIES ARE GOING TO BE FUNDED IN 2018, MID TO LATE 2018, OR EVEN EARLY 2019, BUT LET'S SAY 2018, AND THEN IT TAKES ABOUT FOUR TO FIVE YEARS TO COMPLETE THE WORK, SO THAT TAKES YOU TO 2022. 2023, AND THEN ANOTHER YEAR UNTIL THE RESULTS GET REPORTED. WE'RE NOT QUITE THERE YET. WE WILL BE THERE PRETTY SOON TO TAKE A LOOK AT REGISTRATION, HOW WELL WE'RE DOING WITH REGISTRATION. THAT WILL PROBABLY BE MAYBE A YEAR OR TWO AWAY BEFORE WE CAN SAY SOMETHING MORE CONCRETE ABOUT THAT. >> I THINK THAT WILL BE QUICKER. YOU'VE SEEN WHAT HAPPENS IN INSTITUTIONS LIKE OURS BECAUSE OF WHAT HAS COME OUT. WE'RE ALREADY HAVING TO DO THIS. IT'S JUST -- I'D BE SHOCKED IF YOU DIDN'T SEE IT IN A YEAR. >> I'M WONDERING HAS THERE BEEN ANY EFFORT TO FIND OUT WHY THERE'S BEEN SOME OF THESE DELAYS IN PUBLICATION? LIKE, YOU KNOW, AS A SCIENTIST WHO EXPERIENCED THAT MYSELF I THINK WE ALL HAVE SOME THINGS THAT DON'T GET OUT AS FAST AS WE'D LIKE BUT THERE MIGHT BE SOME GOOD REASONS IN THERE. SOMETIMES INVESTIGATORS LEAVE INSTITUTIONS, THERE'S A LOT OF REASONS. HAVE THERE BEEN EFFORTS TO LOOK AT THAT? PART OF THE SOLUTION MIGHT BE AN UNDERSTANDING OF WHY IT'S HAPPENING. >> SO, YOU KNOW, IT'S BEEN REMARKABLY REPRODUCIBLE, THESE DELAYS IN PUBLICATION. IN FACT, WE FOUND PAPERS GOING BACK TO THE LATE '80s SHOWING EXACTLY THE SAME THING. AND THIS PHENOMENON CUTS ACROSS ALL DIFFERENT FIELDS. IF WE HAD HAD THE OPPORTUNITY TO DO OUR STUDY OVER AGAIN, WE WOULD HAVE SYSTEMATICALLY ASKED PEOPLE ABOUT THEIR TRAJECTORY TO PUBLICATION BUT WE WERE SO SURE WE KNOW THE RIGHT ANSWER WE DIDN'T BOTHER TO ASK. SO BUT WE DID GET A NUMBER -- ENOUGH ANECDOTES THAT YOU COULD COME UP WITH SOME HYPOTHESES. ONE PROBLEM IS THAT SOME SCIENTISTS AIM TO GET THEIR PAPERS PUBLISHED IN INAPPROPRIATE JOURNALS, THEY THINK IT'S IDEAL FOR "LANCET" OR "NEW ENGLAND" WHEN IT ISN'T AND THEY LOSE A LOT OF TIME BECAUSE OF THAT. SOMETIMES THE JOURNALS ARE SLOW TO PUBLISH THEIR -- TO REVIEW AND PUBLISH THEIR RESULTS. SOME OF OUR SCIENTISTS, I'M SURE THIS ALL RESONATES, AFTER THE THIRD TRY SAID WE'VE HAD ENOUGH. AND, YOU KNOW, LET'S MOVE ON TO SOMETHING ELSE. ONE OF THE REASONS WHY WE DECIDED TO FOCUS OUR POLICY ON REPORTING ON clinicaltrials.gov AS DIFFICULT AS IT MAY BE IS THAT WE DON'T REJECT THE STUDIES. IT HAS TO BE PROPERLY FORMATTED AND SO FORTH BUT WE'RE NOT GOING TO SAY WE DON'T THINK THE STUDY IS INTERESTING, OR WE DON'T BELIEVE YOUR RESULTS, OR WE DON'T THINK YOU DID YOUR ANALYSIS CORRECTLY. AND SO WE WANTED TO GET AROUND THAT PROBLEM. THAT WAS ALSO NOT A TRIVIAL ISSUE BECAUSE WE HAD TO HAVE SOME FAIRLY INTENSE CONVERSATION WAS JOURNAL EDITORS AND CONVINCE THEM AND HAVE THEM BE CONVINCED THIS DID NOT CONSTITUTE PRIOR PUBLICATION. AND THAT A REAL FEAR IS RESULTS WOULD GET POSTED IN clinicaltrials.gov AND JOURNALS WOULD SAY NOW WE'RE DEFINITELY NOT GOING TO PUBLISH BECAUSE YOU'VE ALREADY PRODUCED YOUR RESULTS. I DON'T THINK THERE'S A GOOD SATISFACTORY ANSWER TO THAT. IT'S A GREAT QUESTION. I'M NOT SURE WE TOTALLY UNDERSTAND THAT STUDY COMPLETION TO PUBLICATION ECOSYSTEM, NOT SURE WE KNOW IT ALL THAT WELL. >> I WOULD HYPOTHESIZE IT'S A FRONT-END PROBLEM AND I THINK, YOU KNOW, HISTORICALLY NIH FUNDED THROUGH THE R01 MECHANISM, NOT THE BEST FOR A CLINICAL STUDY, AND BY MOVING TO THESE PHASED AWARDS, HUGE UH3s, GIVING THE INVESTIGATOR A YEAR OR TWO I THINK FOR THE V.A., THE NIH/VA/COLLABORATORY GAVE TWO YEARS TO PLAN STUDIES TO FIGURE OUT HOW TO USE ELECTRONIC HEALTH SYSTEMS, FIGURE OUT WHAT THE PATIENT POPULATION IS, WHAT THE -- TO CONTACT THE SIDES TO BE SURE THERE'S ADEQUATE POPULATION, ON R01, THE CLOCK IS TICKING. CATHY COULD COMMENT, YOU HAVE DATA, WHEN YOU GET THE R01 AWARD IT MAY BE A YEAR OR TWO OR THREE BEFORE YOU START RECRUITING AND TIME IS UP FOR YOUR COMPETITIVE RENEWAL. WHAT WE'VE DONE IS WE HAVE LEARNED WE NEED TO BUILD IN START-UP TIME, UH3, UG3 HAS BEEN A GAME CHANGER CONDUCTING CLINICAL RESEARCH. >> CERTAINLY IT'S A GAME CHANGER IN THE CENTER. MANY OF US WHO WORKED IN I.C.s REALIZED EVEN THE U01, MORE COMMONLY USED FOR LARGE CLINICAL TRIALS, HAS ITS LIMITATIONS, SORT OF THE WAY THE BUDGETS ARE STRUCTURED AND TIME ELEMENT. SO THE -- OUR EXPERIENCE WITH THE TRANSITION AWARDS, NOT ONLY FOR PRAGMATIC CLINICAL TRIALS BUT WE ALSO HAVE EXPLANATORY TRIALS LARGE SCALE THAT WE'VE SUPPORTED WITH THE SIMILAR STRATEGY, AND I THINK YOU'RE ABSOLUTELY CORRECT, IT GIVES THE INVESTIGATORS A YEAR, SOMETIMES TWO, TO PLAN AND TO REALLY GET THEIR DUCKS IN A ROW AND MORE IMPORTANTLY TO PROVIDE COMPELLING EVIDENCE TO THE NIH THAT THEY ARE REALLY READY TO START. WE TYPICALLY DO ADMINISTRATIVE REVIEWS AND GENERALLY WILL LOOK FOR EXTERNAL ADVICE AS WELL BEFORE WE'RE READY TO REALLY LAUNCH AND IMPLEMENT A LARGE SCALE TRIAL. CLEARLY PROBLEMS STILL CROP UP BUT AT LEAST WE'RE CLEAR THE OBVIOUS PROBLEMS THAT PLAGUE MANY CLINICAL TRIALS HAVE BEEN ADDRESSED BEFORE WE REALLY COMMIT TO FUNDING A LARGER AWARD. >> FOR US AS A SMALLER CENTER, AND WITH, YOU KNOW, AT THE BEGINNING WE HAD A GROUP OF INVESTIGATORS THAT WERE ACTUALLY LEARNING THE PROCESS. IN TRYING TO ADAPT TO OUR SMALLER BUDGET WE HAD ACTUALLY THREE-YEAR PROCESS FOR SOME OF THE CLINICAL STUDIES WHICH TURNED OUT TO BE A COMPLETE DISASTER. SO WASN'T ENOUGH MONEY AND ENOUGH TIME. SO THOSE WERE THE GROWING PAINS FOR THE CENTER. >> IN TERMS OF AMOUNT OF TIME AND RESOURCES, THE RESOURCES ACTUALLY ENDED BEFORE THE PROJECT ENDED. AND I REALLY WANT TO SAY, DR. LAUER, WHEN THINGS DIDN'T GET PUBLISHED IS THAT ALL OF THE RESOURCES ENDED FOR THE ANALYSIS OF SOME OTHER COMPONENTS TO BE DONE, AND AFTER SPENDING THAT MUCH TIME WHEN PEOPLE ACTUALLY DON'T PUBLISH IT, IT MEANS SOMETHING ELSE HAS HAPPENED, AND I WOULD LIKE TO KNOW SOME INDICATION OF WHAT IT IS. AND AT LEAST IN OUR HANDS A LOT OF IT WAS WE COULDN'T GET ALL THE WORK DONE, WITH THE TIMING AND RESOURCES, ESPECIALLY FOR SMALLER GRANTS, R01s, YOU'RE RUNNING TO CATCH UP. WITH OVERSIGHT PEOPLE ASK YOU TO DO THINGS YOU INCIDENT PUT IN THE BUDGET IN THE FIRST PLACE. HAVE YOU LESS TIME, LESS BUDGET, MORE OVERSIGHT WHICH CONFLATES TO AN IMPOSSIBLE SITUATION. >> THAT WAS THE EXPERIENCE ACROSS THE NIH WITH THE R21 MECHANISM. ONCE IT WAS -- YOU KNOW, IT BECAME A VERY POPULAR MECHANISM TO COLLECT PRELIMINARY DATA, BUT I THINK THE MECHANISM WAS NOT ENOUGH TIME, NOT ENOUGH MONEY FOR INVESTIGATORS, AND FRUSTRATING FOR THE NIH AS WELL. MANY STUDIES DIDN'T GET COMPLETED. >> THAT'S WHY WE NOW HAVE OUR SORT OF TAILORED FUNDING MECHANISMS FOR CLINICAL RESEARCH, AND MUCH OF THAT REVIEW IS DONE IN HOUSE. WE'RE LEARNING IN THIS PROCESS, RIGHT? IT WAS PAINFUL TO GO THROUGH THINKING EVERYTHING COULD GO THROUGH AN R01 MECHANISM. WE'RE LEARNING THAT'S CERTAINLY NOT THE CASE BUT WE'RE MAKING TREMENDOUS STRIDES THINKING ABOUT LOU TO FUND CLINICAL RESEARCH THAT'S MORE PRODUCTIVE FOR THE INVESTIGATOR AND FOR CERTAINLY NIH. YEAH, JEAN? >> QUICK FOLLOW-UP. SO THE POINTS, GIVEN ALL THE INFORMATION WE NOW HAVE, I THINK MAKING SURE THE SCIENTIFIC COMMUNITY UNDERSTANDS WHY YOU ASKING FOR WHAT AND WHY WE'RE CHANGING WHAT IT IS AND NOT JUST TRANSPARENT WAY BUT WAY THAT DISSEMINATES TO PEOPLE SO THEY ACTUALLY GET THE INFORMATION, THEY WILL BE MORE IN LINE TO SAY, OH, I GET IT NOW. YOU'VE FOUND GOOD INFORMATION, BUT JUST THINKING OF OUR STUDY, OH MY GOODNESS, I KNOW WHY YOU DID IT A PARTICULAR WAY. IT ALLOWS US TO GO ALONG WITH YOU BECAUSE WE HAVE SOME UNDERSTANDING WHY YOU'RE ASKING AND THE TIME. >> THANK YOU. THAT'S VERY INSPIRING ALSO. WE'LL KEEP MOVING. BUT I THINK YOUR POINT IS ABSOLUTELY SPOT ON. AND WE'RE NOT YET EVEN AT THE POINT WHERE WE'RE READY TO SHARE WHAT WE HAVE WITH OUR COLLEAGUES YET BECAUSE WE'RE STILL IRONING OUT THE KINKS. BUT I THINK THAT'S A REALLY GOOD POINT, BEFORE TOO LONG WE WILL BE ABLE TO MAKE THAT INFORMATION PUBLIC, JUST LIKE WE DID WITH THE RCDC INCLUSION, MADE THAT PUBLIC. I THINK THAT TURNED OUT TO BE QUITE VALUABLE AND WE'VE ACTUALLY RECEIVED SOME VERY INTERESTING FEEDBACK ON THAT. SO I THINK YOUR POINT IS ABSOLUTELY SPOT ON. >> GREAT. THIS HAS BEEN A GOOD DISCUSSION. ANY OTHER COMMENTS OR QUESTIONS? IF NOT WE'LL MOVE ON TO -- OH YES. >> I WAS WONDERING ABOUT THE R61, ALSO TIME LINE TWO YEARS, LOW BUDGET, IS THAT AFFECTING THE POSSIBILITIES OF FINISHING ANYTHING IN TIME? >> SO WE HAVE THOSE TRANSITION AWARDS, WHERE WE HAVE THE TWO-YEAR AREA WHERE THE INVESTIGATORS, YOU KNOW, ARE STUDYING WHAT TARGET, TARGET ENGAGEMENT, AND COME BACK. >> GOAL, NO GOAL, YOU HAVE TO GET IN TWO YEARS DATA TOGETHER, ANALYZED BEFORE YOU GO TO THE NEXT PHASE. >> YEAH. >> IT'S A KILLER. >> IT IS. IT'S CHALLENGING. BUT I THINK FROM THE OUTSET THOUGH THERE'S SOME MILESTONE THAT'S BEEN AGREED UPON THAT, YOU KNOW, YOU CAN WORK ON. >> WELL, THERE ARE TRANSITION AWARDS AND THERE ARE TRANSITION AWARDS. UG3, UC3 HAS A HIGH RATE OF CONVERSION BY CLINICAL DESIGN. WE WANTED TO BE LAUNCHED, DUCKS ARE IN A ROW, EVERYTHING IS IN PLACE FOR PLANNING, A LOW RISK GRANT. R61, R33 IS HIGH RISK, HIGH FAILURE IN THE SENSE THAT WE'RE ASKING -- R61 IS EXPLORATORY DEVELOPMENTAL PHASE, WE EXPECT MANY NOT TO TRANSITION. AND SO BUT THE FLIP SIDE, IT GIVES INVESTIGATOR AN OPPORTUNITY TO REALLY TRY SOMETHING NEW, INNOVATIVE AND NOVEL THAT THEY MIGHT NOT OTHERWISE HAVE AN OPPORTUNITY TO TRY, UNDER TRADITIONAL R01, FOR EXAMPLE. THERE REALLY ARE DIFFERENT FLAVORS OF THESE TRANSLATIONAL AWARDS DEPENDING WHAT WE'RE TRYING DO AND WHERE YOU ARE IN THE PIPELINE FOR THE EARLY DISCOVERY VERSUS EFFICACY AND PRAGMATIC, SO JUST KEEP THAT IN MIND, IT'S WHAT WE'RE TRYING TO DO HERE. >> YEAH, AND A LITTLE BIT ABOUT PERHAPS THESE GRANTS ARE NOT TERMINAL OR NOT KILLERS NECESSARILY. INVESTIGATORS FREQUENTLY I THINK ACROSS THE NIH AND CERTAINLY WITHIN THE COLLABORATORIES AND OUR PORTFOLIO, INVESTIGATORS SOMETIMES NEED A BIT MORE TIME. AND SO THERE IS SOME FLEXIBILITY WITH ADEQUATE PROGRESS DURING THE EARLY PHASE, BE IT PLANNING, THERE'S USUALLY NOT A LOT OF CLINICAL ACTIVITY VERSUS AN R 6 1 OR ANOTHER TRANSITION GRANT WITH A SMALL CLINICAL STUDY HAPPENING FIRST, IF THERE'S A NEED FOR ADDITIONAL TIME. NOT ADDITIONAL FUNDING TYPICALLY BUT ADDITIONAL TIME TO GET THE WORKED FINISHED. >> I WANT TO OFFER UP WE WANT TO THINK ABOUT ADDITIONAL FUNDING FOR STUFF THAT MAKES SENSE TO YOU. YOU CAN'T HAVE A IT AVAILABLE TO EVERYBODY ELSE BUT IF THEY ARE DOING WHAT THEY ARE SUPPOSED TO BE DOING, THEY DON'T HAVE RESOURCES TO HIRE THE EXTRA PERSON BECAUSE THEY HAVE TO PAY SOMEONE FOR THE TIME, THE TIME WAS TICKING IF YOU DIDN'T GET EVERYTHING DONE, HAVING A FLEXIBLE MODEL TO APPROACH THAT AND THINK ABOUT IT BECAUSE FOR THE MOST PART THEY HAVE TO PAY SOMEBODY, SO WHEN YOU GET TO NO COST EXTENSION IT'S FINE IF YOU HAVE SOMETHING ELSE GOING ON, THOSE PEOPLE TAKE ON ADDITIONAL WORK, WHAT WE DO IN OUR LAB. IF THAT DIDN'T HAPPEN, THERE'S NOT A RESOURCES TO DO IT FOR THE YOUNGER FACULTY, I THINK THAT MIGHT BE A BURDEN. >> I THINK PCORI HAS SOMETHING LIKE THAT WHICH YOU'RE PROBABLY AWARE OF, GETTING TO THE END, RUNNING OUT OF MONEY, NEED EXTRA TIME TO WRITE THINGS UP YOU CAN ASK FOR A LITTLE EXTRA MONEY. KNOWN IF NIH HAS THAT OPTION BUT . >> SUPPLEMENTS, BRIDGE FUNDING. WE CAN ENTERTAIN THOSE OPPORTUNITIES UNDER THE R61, R33. HIGH RISK, HIGH REWARD, HIGH FAILURE WAS BUILT INTO THE R61, THE IDEA IS TO GIVE A LITTLE BIT OF MONEY TO TEST AN IDEA, IN SHORT PERIOD OF TIME, NOT TO DO A FULL FLEDGED STUDY BUT REALLY TO GET THE CORE PRINCIPLES AND SIGNAL AND SOME KINKS WORKED OUT OF THE INNOVATIVE PROJECT, THEN MOVING INTO A LARGER SCALE STUDY. WE REALLY ARE NOT EXPECTING A LOT OF THESE TO TRANSITION BUT WE'RE GIVING THE INVESTIGATOR AN OPPORTUNITY TO EXPLORE SOMETHING NEW AND NOVEL. UNLIKE THE CLINICAL TRIAL WHICH IS DIFFERENT. >> YEAH, I'D LIKE TO MAKE A COMMENT, MORE GENERAL COMMENT. IN RESPONSE TO WHAT JEAN WAS TALKING ABOUT, COMMUNICATION. I USED TO BE AN INVESTIGATOR, I KNOW HOW LONG IT'S TAKEN ME IN THIS POSITION TO EVEN UNDERSTAND ALL OF IT. YOU KNOW, SERIOUSLY. I MEAN, THESE ARE NOT SIMPLE THINGS. I THINK THERE'S A DIFFERENCE, THERE'S TWO STEPS, RIGHT? THERE'S COMMUNICATION. THEN THERE'S ALSO MAKING SURE THAT PEOPLE UNDERSTAND WHAT YOU COMMUNICATED. SO I THINK THIS MAY BE A LOOP THAT WE WOULD REALLY LOVE INPUT FROM YOU ALL AS TO, A, ARE WE COMMUNICATING THIS ENOUGH OR IN THE RIGHT WAY AND HOW CAN WE COMMUNICATE BETTER, HOW CAN PEOPLE UNDERSTAND? WHAT DAVID WAS JUST EXPLAINING, NUANCES BETWEEN THE RISK OF THE R61 VERSUS RISK OF UG3, I'M NOT SURE INVESTIGATORS REALLY UNDERSTAND THIS. I MEAN, IT'S SUBTLE BUT IT'S IMPORTANT BECAUSE YOU WANT TO MAKE SURE YOU APPLY FOR THE RIGHT MECHANISM. AND SO SOME OF THIS INFORMATION YOU CAN GET BY TALKING ONE ON ONE WITH YOUR PROGRAM OFFICER. BUT I WOULD GUESS YOU HAVE TO KNOW THE RIGHT QUESTIONS TO ASK. WE HAVE INFORMATION SESSIONS, WEBINARS, BUT A LOT OF TIMES, YOU KNOW, JUST IT'S SO MUCH. IT GOES OVER YOUR HEAD. ANY FEEDBACK FROM YOU ALL HOW TO EXPLAIN THIS BETTER WOULD BE REALLY, REALLY WELCOME. >> THAT SILENCED THE ROOM. [LAUGHTER] YOU'RE ALWAYS WELCOME TO COME AND SHADOW US FOR MAYBE A YEAR OR TWO. >> YEAH, RIGHT. >> NO, I THINK IT'S ALSO A PARTNERSHIP. WE DO WHAT WE DO. IT'S A SYMBIOTIC RELATIONSHIP. WE CAN'T MOVE FORWARD WITHOUT THE EXPERTISE YOU HAVE BUT I DON'T HAVE THE KNOWLEDGE YOU HAVE TO DO THE RESEARCH YOU DO. LIKEWISE, FOR BETTER OR WORSE, WE'RE GOVERNMENT EMPLOYEES WHO UNDERSTAND THIS LARGE BUREAUCRACY OF NIH, AND TRYING TO DO OUR BEST WITH TAXPAYER DOLLARS. SO I THINK WE JUST HAVE TO HAVE A MEETING OF THE MINDS AND COME TO SOME GENERAL UNDERSTANDING AND REALIZE BOTH ASPECTS OF FUNDING AND DOING RESEARCH ARE IMPORTANT. AND WE NEED TO JUST BE ABLE TO WORK THROUGH THESE CHALLENGES BUT I DON'T THINK THEY ARE GOING TO GO AWAY, JUST HOW CAN WE BETTER WORK TOGETHER I THINK IS THE OTHER ASPECT. SO IT'S NOT US/THEM. IT'S US AS AN ENTERPRISE, BOTH AS EXTRAMURAL RESEARCHER AND AS GOVERNMENT OFFICIALS, YOU KNOW, STEWARDS OF TAXPAYER DOLLARS. WE WANT TO DO THE BEST FOR BOTH, THE SCIENCE AND THE PUBLIC TRUST. SO IT'S THAT BALANCE WE HAVE TO GET RIGHT, AND I COMPLETELY ACKNOWLEDGE THAT WE DON'T ALWAYS GET IT RIGHT AND IT CAN BE EXTREMELY FRUSTRATING, FROM OUR PERSPECTIVE GOVERNMENT EMPLOYEES, I CAN'T IMAGINE WHAT IT'S LIKE BEING AN EXTRAMURAL SCIENTIST HAVING TO DEAL WITH THIS MONOLITH CALLED THE NIH. I COMPLETELY UNDERSTAND AND THAT'S WHY WE'RE HERE TO HELP. YES, SO -- YES, LET'S GO TO THE NEXT PART. >> WE ARE GOING TO -- IN THE SECOND PORTION OF THE TALK WE'RE GOING TO DELVE MORE INTO THE PROCESS, REALLY HOW WE DO THINGS, WHO IS ACTUALLY DOING MOST OF THE WORK, AND THE KIND OF INTERACTION THAT IS INVOLVED IN BOTH ASPECTS OF THE PROCESS, PRE-AWARD AND POST-AWARD ACTIVITY, AND ALSO WHAT KIND OF RESOURCES THAT WE HAVE IN PLACE FOR THE INVESTIGATORS. SO, WE'RE GOING TO CONTINUE THE SAME TAG TEAM APPROACH. I'M GOING TO TALK ABOUT THE PRE AND POST AWARD PROCESS, BUT SOME OF THE ELEMENTS INCLUDED INTO EACH OF THOSE STEPS, WHAT KIND OF INTERACTION WE HAVE WITHIN THE CENTER BETWEEN THE PROGRAM DIRECTORS AND DIVISION OF EXTRAMURAL RESEARCH, CATHY'S STAFF FROM THE OFFICE OF CLINICAL AND REGULATORY AFFAIRS AND OUR GRANTS MANAGEMENT STAFF THAT ISSUED THE AWARD. SO, WHAT IS INVOLVED IN OUR PRE-AWARD PROCESS? SO IN PREPARATION FOR COMING TO COUNCIL, WITH RECOMMENDATIONSES FOR FUNDING, THERE'S A LOT OF ACTIVITIES THAT TAKES PLACE BEHIND THE SCENE. AND WE HAVE MANY, MANY DIFFERENT STEPS WHERE THERE'S A LOT OF CHECKS AND BALANCES BEFORE WE COME TO YOU WITH THE RECOMMENDATION FOR FUNDING. FIRST OF COURSE WE HAVE THE PEER REVIEW PROCESS, APPLICATIONS ARE REVIEWED, AND THIS IS THE FIRST ASSESSMENT OF NOT ONLY SCIENCE AND APPROACH BUT ONCE WE GET THE OUTCOME FROM THE PEER REVIEW PROCESS THERE'S AN AWFUL LOT OF WORK THAT STAFF AT NCCIH GOES THROUGH BEFORE WE ACTUALLY PRESENT AN APPLICATION TO YOU FOR FUNDING. SO, IT'S A REAL COLLABORATION BETWEEN PROGRAM STAFF AND THE OFFICE OF CLINICAL AND REGULATORY AFFAIRS. SO THE DISCUSSIONS THAT WE HAVE, CONSIDERATIONS THAT COME INTO PLAY REALLY INCLUDE PROGRAM PRIORITIES. I MEAN, WE KNOW WHAT'S IN THE PORTFOLIO. WE HAVE A GOOD SENSE OF WHERE THE FIELD IS GOING. SO THOSE DISCUSSIONS REALLY INCLUDE THAT KIND OF PROGRAMMATIC BALANCE AND RELEVANCE TO NOT ONLY, YOU KNOW, STUDY IN GENERAL BUT ALSO TO THE FIELD. WHAT'S PROMISING, WHERE DO WE WANT TO GO? WE CERTAINLY TAKE INTO ACCOUNT IRG RECOMMENDATION AND CONCERNS. AS PART OF THOSE DISCUSSIONS, PROGRAM DIRECTORS WOULD ALWAYS ASK THE INVESTIGATORS TO RESPOND IN WRITING TO SOME OF THE COMMENTS OR, YOU KNOW, CONCERNS THAT WERE HIGHLIGHTED IN THE PEER REVIEW PROCESS. NOW, AS I MENTIONED, STAFF HAS A VERY GOOD KNOWLEDGE OF THE ONGOING WORK IN THE PORTFOLIO. WE HAVE ABILITY TO ACTUALLY HAVE SOME INSIGHT INTO WHAT DIRECTION PROPOSED STUDY IS ACTUALLY GOING. SO BETWEEN CATHY'S STAFF AND MY STAFF, THERE'S A LOT OF VERY CAREFUL DISCUSSION ABOUT THE AIMS OF THE STUDY, ANALYTIC PLAN, RECRUITMENT PLANS, ALSO THE DATA AND SAFETY MONITORING PLAN. THE PRIMARY FOCUS OF THE PRE-AWARD PROCESS AGAIN BEFORE WE COME AND COMMAND A STUDY FOR FUNDING WE WANT TO MAKE SURE THAT IT'S GOING TO, YOU KNOW, BE WITHIN THE PRINCIPLE OF RIGOR, SCIENTIFIC RIGOR, IMPACT, AND WHETHER THE STUDY COULD BE DONE. YOU COULD HAVE A VERY INTERESTING STUDY BUT IF IT'S NOT GOING TO BE FEASIBLE OR NOBODY'S GOING TO ACTUALLY ADHERE TO THE INTERVENTION, THEN IT WOULD BE POINTLESS FOR US TO FUND IT. SO, THE POINT THAT I REALLY WANT TO MAKE IS THAT IT'S ALWAYS WITH THE INTENT THAT THE STAFF WOULD ENGAGE INTO A DIALOGUE WITH THE INVESTIGATOR. SO THAT IS REALLY IMPORTANT. WE ALWAYS WANT TO EMPHASIZE THAT WE HAVE A PARTNERSHIP WITH THE INVESTIGATIVE TEAM AND THAT WE HAVE THEIR BEST INTERESTS AT HEART WHEN WE HAVE THOSE CONVERSATIONS. SO THERE ARE SOME PARTICULAR ELEMENTS TO THE PRE-AWARD PROCESS SO WE HAVE CLARIFICATION LETTER, IN THE CASE OF TRANSITION GRANT AS WE WERE JUST TALKING ABOUT THERE IS SOME MILESTONE THAT NEEDS TO BE, YOU KNOW, ACHIEVED BEFORE THERE IS A SWITCH TO THE OTHER PHASE, SO AGAIN THERE'S SOME NEGOTIATION ABOUT WHAT KIND OF MILESTONE, HOW AGREEABLE THEY ARE TO THE P.I. AND THEN OF COURSE THERE IS SOME STUDY ACCRUAL AND RETENTION PLAN, WE TALKED ABOUT DIFFICULTY IN STUDIES, NOT RECRUITING AND RETAINING PARTICIPANTS. AND I MENTIONED EARLIER WE ALSO HAVE VERY RICH CLINICAL RESEARCH TOOLBOX THAT IS A RESOURCE FOR INVESTIGATORS. WHO DOES WHAT? I MEAN, SO WE HAVE A LOT OF INTERACTION HERE BUT THERE'S SOME RESPONSIBILITIES THAT ARE ASSIGNED TO SPECIFIC PEOPLE. CLARIFICATION LETTER ESSENTIALLY THE PROGRAM DIRECTOR, MY STAFF, ARE RESPONSIBLE FOR PRIMARY INTERACTION WITH THE INVESTIGATORS. SO, IF THERE'S ANY QUESTION ABOUT SOME ASPECT OF THE PROJECT, INCLUDING THE MILESTONE FOR TRANSITION GRANT, THE PROGRAM DIRECTOR IS THE ONE THAT ACTUALLY INQUIRIES AND GETS IN CONTACT WITH THE INVESTIGATORS. AND WE REQUIRE WRITTEN RESPONSE TO THOSE, YOU KNOW, COMMUNICATIONS BECAUSE WE DON'T WANT TO HAVE A PHONE CALL AND THEN NOBODY REMEMBERS WHAT WAS AGREED UPON SO WRITTEN RESPONSE IS USUALLY REQUESTED. SO, CATHY IS GOING TO LATER ON TALK IN MORE DETAIL ABOUT THE SOFT PROCESS, STUDY ACCRUAL AND RETENTION PLAN AND DSMP, DATA SAFETY MONITORING PLAN. AT THE TIME, THOSE REQUESTS ARE MADE OF THE INVESTIGATOR. ALSO, THIS IS A TIME FOR PROGRAM STAFF TO REMIND INVESTIGATORS OF SOME OF THE REQUIREMENTS. WE JUST TALKED ABOUT clinicaltrials.gov. SO WE REMIND THEM THAT THEY NEED TO REGISTER THEIR STUDY. IF, FOR EXAMPLE, THEY DID AN IND, THIS IS THE TIME TO LET THEM KNOW THEY NEED TO HAVE PRE-DISCUSSION, IF THERE ARE SIGNIFICANT CHANGE IN THEIR STUDY THAT WE REMIND THEM THAT THEY ARE GOING TO NEED TO GET APPROVAL FROM NCCIH BEFORE THEY ACTUALLY GO AHEAD AND MAKE THE CHANGE. AND WE ALSO LET THEM KNOW AT VARIOUS POINTS DURING THE LIFE CYCLE OF THE GRANT WE'RE GOING TO ASK THEM FOR ACCRUAL AND MONITORING REPORTS SO THEY HAVE AN IDEA OF, YOU KNOW, THE PROCESS THAT THEY ARE GOING TO UNDERGO. NOW, FOR ENHANCED OVERSIGHT, THERE'S ADDITIONAL MATERIAL THAT'S REQUESTED SO FOR EXAMPLE STUDY DOCUMENT THAT INCLUDES PROTOCOL AND ALSO TIME LINE FOR IMPLEMENTATION IS ASKED AT THAT POINT. IF THOSE GRANTS ARE GOING TO HAVE THE ON-SITE MONITORING PROGRAM THAT'S AN IDEA TO GIVE THEM IDEA WHAT TO EXPECT AND THE TIMELINE. SO, IN ADDITION TO THE PRE-AWARD PROCESS NOW WE'VE COME TO COUNCIL, NOW IT'S FUNDED. THERE'S A SET OF ACTIVITIES POST-AWARD. AGAIN, HERE IS ACTUALLY EVEN MORE PLAYERS INVOLVED. WE HAVE PROGRAM STAFF, WE HAVE OCRA STAFF AND GRANTS MANAGEMENT. THERE'S DIFFERENT FLAVORS DEPENDING ON THE OVERSIGHT LEVEL. SO FOR ENHANCED OVERSIGHT STUDY, I ALREADY MENTIONED THAT WE'RE GOING TO REQUEST ADDITIONAL DOCUMENTS. WE'RE GOING TO REQUEST THE PROTOCOL IS SUBMITTED TO US. THIS IS AGAIN AN ITERATIVE PROCESS, AND I THINK INVESTIGATORS SOMETIMES DON'T PREFER TIME INVOLVED BECAUSE THEY SUBMIT SOMETHING TO US, STAFF HAS TO REVIEW IT, MAKE SOME COMMENTS, SEND IT BACK, SO THAT TAKES TIME. AND THEN THERE IS THE ON-SITE MONITORING PROGRAM IF IT'S APPLICABLE WHERE WE SEND A TEAM TO ACTUALLY ASSESS WHETHER THERE IS ALL CRITICAL ELEMENTS NEEDED FOR THE SUCCESS OF THE STUDY. NOW, POST-IMPLEMENTATION FOR ALL PROJECTS WE TALKED ABOUT STUDY ACCRUAL AND RETENTION PLAN, REALLY IMPORTANT BECAUSE THERE WILL BE MANY SITUATIONS WHERE INVESTIGATORS HAVE THE BEST INTENTIONS BUT FOR SOME REASON THEY MIGHT BE COMPETING INTERESTS WITHIN THE INSTITUTION FOR PARTICIPATING IN A STUDY OR MIGHT BE VERY DIFFICULT POPULATION AND THEY ARE STRUGGLING. BUT HAVING THIS THOUGHT PROCESS WE'RE ABLE TO KEEP -- TO TRACK THEIR PROGRESS AND AT TIMES WE HAVE SITUATION WHERE WE NEED TO INTERVENE AND MAYBE SUGGEST SOME DIFFERENT STRATEGIES. AND THIS IS OUR WAY TO BE PRO-ACTIVE SO WE CAN ANTICIPATE UNDERLYING PROBLEM WITH COMPLETION OF THE STUDY. SO THE STUDY DOCUMENTS, THE LATTER IS SENT BY THE PROGRAM DIRECTOR FOR ENHANCED OVERSIGHT BUT, AGAIN, EVEN THOUGH THE LETTER IS SENT BY THE PROGRAM DIRECTOR IT'S ALWAYS IN COLLABORATION WITH OUR COLLEAGUE AT THE, YOU KNOW, IN OCRA. AND WE TRY AS MUCH AS POSSIBLE TO INFORM THE INVESTIGATORS OF THE TIMELINE. WE REMIND THEM OF THE ON-SITE MONITORING TASK. ALL OF THIS IS DONE WITH THE INTENT OF MAXIMIZING SUCCESS FOR THE STUDY. THE STUDY DOCUMENT SUBMISSION ESSENTIALLY THE PRINCIPAL INVESTIGATOR HAS THE RESPONSIBILITY TO SUBMIT PROTOCOL AND ASSOCIATED STUDY DOCUMENTS. THE SARP AND DSMP. THIS IS AN ITERATIVE PROCESS. THERE'S STILL SOME CLARIFICATION THAT NEEDS TO BE PROVIDED. AGAIN, SO THIS IS BACK AND FORTH. THERE IS COLLABORATION ACROSS THE BOARD AT NCCIH AND ALSO WITH THE INVESTIGATORS. SO I HOPE YOU'VE GOTTEN A SENSE OF HOW MUCH WORK GOES INTO THIS PROCESS. THIS IS REALLY NOT FOR THE FAINT OF HEART. WE ALL GET VERY INVOLVED. IT REALLY DOES TAKE A VALUING. >> THAT'S TRUE. THANK YOU VERY MUCH, EMMELINE. I THOUGHT WE WOULD TAKE A BIT OF TIME TO TALK ABOUT A COUPLE ASPECTS OF SOME OF THESE POST-AWARD PROCESSES AND DRILL DOWN WITHOUT ALARMING FOLKS WITH TOO MUCH DETAIL. THE FIRST ONE, WE WANTED TO BRING TO YOUR ATTENTION, THE RATIONALE FOR ON-SITE MONITORING PROGRAM, WHY WE PUT THIS PROGRAM TOGETHER WHICH REALLY BEGAN IN EARNEST IN THE CENTER IN 2012. AND I THINK THAT IT REALLY WAS CONSISTENT WITH THIS OVERALL OVERSIGHT STRATEGY THAT WE HAD DISCUSSED IN THE FIRST PART OF OUR TALK WHERE OUR LARGER TRIALS THAT WERE PERHAPS MULTI-SITE OR MORE COMPLEX WOULD REALLY BENEFIT FROM THE ADDITIONAL ASPECT OF ON-SITE MONITORING WHEN OUR MONITORS ARE IN THE FIELD THEY CERTAINLY DO AN AWFUL LOT OF EDUCATION WITH STUDY TEAMS, AND AS WE LOOK INTO THE FEDERAL REGS AND CERTAINLY GCP PERHAPS, IT GIVES THE PRIMARY PURPOSE OF MONITORING IS TO VERIFY THE SAFETY, THE RIGHTS AND WELT -- ANDS WELL BEING OF PARTICIPANTS, DATA INTEGRITY AROUND ACCURACY AND COMPLETELY, VERIFIABLE, SITES THAT ARE PUTTING TOGETHER DATABASES FOR TRIAL RESULT IT'S INDEED DO -- HAVE AN OPPORTUNITY TO DO THAT. AND CERTAINLY COMPLIANCE WITH A NUMBER OF REQUIREMENTS REGARDING PROTOCOL AMENDMENTS AND POLICIES AND CERTAINLY AN APPLICABLE REGULATORY REQUIREMENT WHOSE LIST HAS UNFORTUNATELY GROWN OVER THE LAST DECADE OF CLINICAL TRIALS WORK. SO THIS IS A PROGRAM THAT WE'VE -- PARTICULARLY OVER THE LAST FEW YEARS HAVE TAKEN A VERY SERIOUS LOOK AT HOW WE USE THE MONITORING PROGRAM TO APPLY PROPERLY TO STUDIES IN THE PROGRAM OF THE APPROPRIATE COMPLEXITY, SIZE AND SCALE, AND AS WE MENTIONED BEFORE, A NUMBER OF OTHER CONSIDERATIONS THAT COME INTO OUR THINKING AND ASSIGNING SPECIFIC PROJECTS TO MONITORING. AND I DID ALSO WANT TO TALK ABOUT A SECOND ASPECT, THE SARP, INTRODUCED BY EMMELINE, THE STUDY ACCRUAL AND RETENTION PLAN. THIS IS AN ACTIVITY THAT BEGAN IN OUR PORTFOLIO WITH ANY GRANTS THAT WERE FUNDED JANUARY 1, 2017, AND BEYOND. AND IT'S AN ACTIVITY THAT REALLY ALLOWS EVERYONE TO CLARIFY THE GOALS AND THE TIMELINE OF A PROJECT BEFORE IT'S INITIATED. THESE SARPs ARE COMPLETED BY P.I.s AND THEIR INSTITUTION, AND THEY PROVIDE ALL THE STAKEHOLDERS HERE, P.I. INSTITUTION AS WELL AS NCCIH, AN UNDERSTANDING OF THE EXPECTATIONS BEFORE THE STUDY BEGINS. AND NCCIH INCORPORATION THIS SARP ACCRUAL PROJECTION PROVIDED INTO AN ELECTRONIC TOOL THAT WE ACTUALLY USE WITHIN THE CENTER TO TRACK WHAT'S HAPPENING IN THE FIELD. AND SO HERE'S AN EXAMPLE OF A SARP TEMPLATE THAT IS DOWN LOADED FROM OUR TOOLBOX. AND IT PROVIDES SIMPLY ACCOUNT NUMBER, OVER TIME, FOR AN INDIVIDUAL PROJECT. PRINCIPAL INVESTIGATORS PROVIDE US WITH A START TIME NEAR THE ORIGIN, AND THEN WE TRACK THESE DATA THAT THEY PROVIDE US OVER THE LIFESPAN OF A CLINICAL TRIAL SO AGAIN THESE ARE NUMBERS, THESE ARE DATES, AND PROJECTS, AND COUNT NUMBERS, IF YOU WILL, THAT ARE PROVIDED TO US BY THE P.I. BEFORE THE STUDY ACTUALLY STARTS. HOW DO WE USE THIS INFORMATION? WE ACTUALLY DO QUITE A BIT OF TRACKING. THE TOOL THAT WE HAVE WITHIN THE CENTER THAT INTERNALLY WE REFER TO THIS AS THE CLIPPER TOOL, BUT THESE ARE DATA THAT ARE PROVIDED BY THE INVESTIGATORS TYPICALLY EVERY FOUR MONTHS, ONCE ACCRUAL HAS STARTED. AND, AGAIN, THE WAY THESE DATA ARE DISPLAYED FOR REALLY ALL THE SCIENTIFIC STAFF IN THE CENTER, WE PROJECT -- YOU KNOW, THE TOOL IMPORTS WHATEVER THE P.I. TOLD US IN TERMS OF EXPECTED TOTAL AND WE FOLLOW ALONG WITH THE STUDY AS IT BEGINS. AND WE REALLY TRACK THREE VARIABLES AS WE'RE LOOKING AT THESE NUMBERS. FIRST IS THE PRE-ENROLLMENT TIME FRAME, OR WHETHER THERE'S ACTUALLY AN ACCRUAL DELAY WHEN INVESTIGATOR TELLS US THEY WILL START, AND HOW CLOSE THIS STUDY ACTUALLY IS TO THAT GIVEN START TIME AND THEN THE ACTUAL ACCRUAL NUMBER THAT OCCURS OVER TIME. AND THEN THE FINAL VARIABLE WE'RE LOOKING AT IS LOSS TO FOLLOW-UP PROJECTIONS, IN PART OF THE ORIGINAL SARP REPORT WE GET ESTIMATES FROM THE INVESTIGATOR BEFORE THE STUDY STARTS AND SO THAT'S ANOTHER VARIABLE THAT'S ACTUALLY TRACKED DURING THE LIFESPAN OF AN INDIVIDUAL STUDY. SO HOW DO WE USE THIS INFORMATION? AND I THINK IN RESPONSE TO ONE OF ERIC'S EARLIER QUESTIONS, THERE'S A LONG HISTORY OF COLLECTING THIS INTERIM ACCRUAL REPORT WITHIN THE CENTER. I ARRIVED IN 2009, AND WHEN I ARRIVED I WAS LOOKING AT OLD SPREADSHEETS THAT DATED BACK TO PERHAPS 2002, WHEN THE CENTER WAS FIRST EMPOWERED TO ISSUE ANY GRANTS, AND WE WERE TRACKING CLINICAL ACTIVITY FROM THE VERY BEGINNING. SO THIS IS INFORMATION WE'VE BEEN ABLE TO PUT INTO AN ELECTRONIC FORMAT THAT ALLOWS US TO MORE READILY TRACK WHAT'S HAPPENING. AND SO I THINK EMMELINE RAISED SOME OF THESE POINTS EARLIER BUT IN ADDITION TO CLARIFYING EXPECTATIONS PRE-IMPLEMENTATION, IT ALLOWS FOR EARLY RECOGNITION OF ACCRUAL PROBLEMS AND EARLY OUTREACH FROM SCIENTIFIC STAFF AT THE CENTER BECAUSE FOLKS WHO HAVE BEEN INVOLVED IN CLINICAL RESEARCH REALLY UNDERSTAND THAT PERHAPS SOMETIMES WHATEVER CAN GO WRONG, WILL, IN CLINICAL WORK. THERE ARE A LOT OF REASONS, BUT PERHAPS FIVE THAT ARE COMMON ACROSS ALL CLINICAL RESEARCH. WE FIND THAT ENROLLMENT CRY TEAR CRITERIA MAY BE RESTRICTIVE, ACCESS TO TARGET POPULATION MAY BE LIMITED FOR A VARIETY OF REASONS, IN AN UNEXPECTED WAY ONCE THE STUDY STARTS. THERE MAY BE COMPETING TRIALS, EITHER WITHIN THE P.I. PORTFOLIO OR WITHIN THE INSTITUTION. THAT THERE MAY BE REAL OBSTACLES. THE NUMBER OF ELIGIBLE PATIENTS FOR WHATEVER REASON MAY MARKEDLY SHIFT, PARTICULARLY -- I MEAN THERE ARE A NUMBER OF REASONS. REGARDLESS OF THE KIND OF TRIAL, WHETHER IT'S AN EFFICACY TRIAL OR OTHER MECHANISTIC STUDY, THESE ARE COMMON CHALLENGES ACROSS STUDIES. AND SO WE'VE ALSO KNOWN FOR FOLKS THAT HAVE BEEN INVOLVED IN CLINICAL RESEARCH THAT THE BEST TIME TO INTERVENE IS EARLY. IF ONE WAITS UNTIL THERE'S ONLY 12 MONTHS LEFT IN A GIVEN AWARD, IT'S REALLY TOO LATE TO HAVE A MEANINGFUL INTERVENTION TO TRY TO IMPROVE RECRUITMENT AND RETENTION. AND SO THE SARP PROCESS ALLOWED THE DEVELOPMENT OF THESE REPORTS WITHIN THE CENTER AND PRETTY REGULAR CONVERSATIONS WITH OUR COLLEAGUES TO LOOK AT WHAT'S HAPPENING, AND WE'RE REALLY FOCUSING ON THAT EARLY PHASE. ONCE PEOPLE HAVE BEEN ENREGULAR -- ENROLLING FOR 12 MONTHS IF WE SEE A DRIFT IT'S TIME TO REACH OUT AND FIND OUT WHAT THEY PERCEIVE AS THE OBSTACLES OR CHALLENGES THEY ARE DEALING WITH SO THAT EARLY INTERVENTION CAN SOMEHOW HELP. THE PLAN IS NOT TO REALLY LIMIT THE ABILITY OF STUDIES TO COMPLETE, QUITE THE REVERSE. YOU KNOW, WE FIND PERHAPS FIVE TO SIX TRIALS A YEAR THAT ARE STRUGGLING VERY EARLY ON, AND I THINK WITH OUT REACH, AND AT LEAST CONVERSATIONS WITH THE NIH, ABOUT WHAT THE DIFFICULTIES MIGHT BE, WE'VE ACTUALLY BEEN VERY ENCOURAGED BY SIGNIFICANT IMPROVEMENT, ONCE INVESTIGATORS KNOW THAT NIH IS THERE REALLY TO TRY TO HELP BECAUSE THIS IS A SHARED RESPONSIBILITY, TO SEE STUDIES COMPLETE, AND COMPLETE ON TIME. SO I THINK THAT THERE WAS A LONG HISTORY OF DOING THIS, AND NOW IN THE DIGITAL AGE WE'RE ABLE TO DO THIS A BIT EASIER AND I THINK THAT IT REALLY IS IMPORTANT FOR US TO KEEP UP AND KEEP EVERYBODY IN THE GREEN, AS THEY WERE. WE LIKE TO SEE EVERYBODY ON TRACK WITH THEIR GOALS. AND THAT'S -- THAT REALLY IS A GOAL FOR EVERYONE. I WANTED TO SPEND A FEW MINUTES ON THESE WEB-BASED RESOURCES WE HAVE. THERE ARE A NUMBER OF RESOURCES FOR RESEARCHERS. CERTAINLY THE TOOLBOX, THE CLINICAL RESEARCH TOOLBOX HAS BEEN UP AND RUNNING FOR SIX OR EIGHT YEARS, IT'S A TOOLBOX WE UPDATE FREQUENTLY AND PUT QUITE A BIT OF RESOURCES WITHIN OCRA AND OUR OFFICE OF COMMUNICATIONS THAT GIVES QUITE A BIT OF ADVICE AND ADDITIONAL RECRUITMENT FOR CLINICAL STUDIES AND RIGOR AND REPRODUCIBILITY. DRILLING DOWN A LITTLE BIT ON THE CLINICAL RESEARCH TOOLBOX, WE HAVE A LOT OF RESOURCES FOR CLINICAL RESEARCH START-UP, A NUMBER OF TEMPLATE DOCUMENTS FOR ALL ASPECTS OF GETTING A TRIAL READY FOR UP AND RUNNING, DOCUMENTS USED DURING THE CONDUCT OF A CLINICAL STUDY, AND QUITE A BIT OF INFORMATION ON THE ON-SITE MONITORING PROGRAM, MILESTONE DOCUMENTS FOR WHAT I SEE IS A GROWING TRANSITION GRANT PORTFOLIO WITHIN THE CENTER, AND THEN SEVERAL OTHER ADDITIONAL TRAINING AND RECRUITMENT RESOURCES. THE ON-SITE MONITORING PROGRAM HAS QUITE A BIT OF INFORMATION, AS I SAID BEFORE. THESE-- THE MONITORS TYPICALLY HAVE THREE KINDS OF SITE VISITS FOR ALL OF OUR STUDIES, THE FIRST IS THE -- THE FIRST IS THE SITE INITIATION VISIT. INTERIM VISIT. CLOSEOUT VISITS, WHICH ARE ALL -- A LOT OF INFORMATION, CHECK LIST FOR EACH OF THOSE VISITS AS WELL AS FAQs AND QUITE A BIT OF INFORMATION TO HELP OUR SITES GET PREPARED FOR THE ARRIVAL OF THE STUDY MONITORING -- MONITORS. IN CLOSING, I WANTED TO PROVIDE A BIT OF GOOGLE ANALYTICS. I THINK THE OFFICE OF COMMUNICATIONS HELPS US THINK ABOUT HOW PEOPLE ARE USING THE WEBSITE, PARTICULARLY THE TOOLBOX. LOOK ACROSS THE TOP, PAGE VIEWS IN THE TOOL'S BOX FOR 2019. WE SEE FOR 2019 WE HAD 35,000 VISITS, OR SO, THE USUAL FOOT TRAFFIC TO THE WEBSITE. AND THESE ARE JUST OVER TIME REPORTS FOR WHAT HAPPENS AND COMMUNICATIONS TELLS ME THIS IS THE USUAL CADENCE THEY SEE WITH THE EBB AND TIDE OF MONDAY THROUGH FRIDAY, PERHAPS SOME SEASONAL VARIATION, MAYBE A SPIKE BEFORE OR AFTER A GRANT REVIEW, SO THAT'S -- YOU KNOW, THIS CERTAINLY IS CONSISTENT WITH WHAT WE'VE SEEN IN THE PAST. IF WE LOOK AT WHO IS PEEKING INTO THE TOOLBOX, I THINK 85% IS USA AND CANADA. AND THE REST OF THE -- CERTAINLY ASIA AND EUROPE WITH PERHAPS 6 TO 7% OF THE FOOT TRAFFIC INTO THE TOOLBOX. AND ONE OBSERVATION THAT I THOUGHT WAS INTERESTING IF WE LOOK AT PAGE VIEWS AND TIMELINE PAGE, WHAT WE OBSERVED IN 2015, AND WHAT WE SEE NOW FROM HISTORY IN 2019, WE'VE REALLY SEEN ALMOST A DOUBLING OF THE PAGE VIEWS INTO THE RESEARCH TOOLBOX, AND THE TIMELINE PAGE IS QUITE LONG. TIME ON PAGE FOR THE CENTER IS LESS THAN HALF OF WHAT WE'RE SEEING HERE, SO IT'S USUALLY ABOUT TWO MINUTES. AND SO PERHAPS NOT UNEXPECTED WE'VE GONE FROM FOUR MINUTES TO SIX MINUTES, WE'VE GOT A RICH RESOURCE. IF YOU THINK THIS IS A DIRECTORY OF MANY KINDS OF DOCUMENTS AND TEMPLATES, REFLECTS THAT PEOPLE ARE USING THE TOOLBOX AS WE EXPECT, THEY ARE IN THERE, NOT DOING THIS ON A MOBILE DEVICE, THESE ARE LIKELY INVESTIGATORS SITTING AT A DESKTOP WITH A MONITOR, AND THEY ARE GOING THROUGH A LOT OF THE DOCUMENTS THAT ARE AVAILABLE FOR THEIR PLANNING AND IMPLEMENTATION OF CLINICAL STUDIES. SO I THINK AT THIS POINT WE'LL STOP FOR A BIT OF DISCUSSION. WE'VE GONE OVER A LOT OF DETAILS IN THE PROCESS. DAVID, DO YOU WANT TO PROVIDE SOME COMMENTS? >> CERTAINLY EMMELINE AND CATHY PEELED BACK THE CURTAIN, AND GAVE YOU INSIGHT INTO HOW WE MAKE AWARDS AND WHAT GOES INTO IT. I THINK YOU CAN HEAR -- YOU'VE HEARD FROM BOTH CATHY AND EMMELINE DEDICATION OF STAFF, AMOUNT OF TIME INVOLVED FROM OUR STAFF, CERTAINLY ON THE INVESTIGATOR SIDE. I THINK THAT REFLECTS TOO NOW WE'VE GONE FROM A LOT OF 90% HIGH OVERSIGHT NOW TO ABOUT 20 OR 30% OVERSIGHT. IT REFLECTS THE FACT THAT AMOUNT OF TIME INVOLVED IN SOME OF THESE PROCESSES WE JUST CAN'T DO IT FOR EVERY CLINICAL APPLICATION. WE REALLY HAD TO CHOOSE AND MAKE HARD DECISIONS ABOUT WHERE TO INVEST THOSE STAFF RESOURCES AND WHERE IT'S IMPORTANT TO COMMUNICATE WITH THE INVESTIGATORS. SO A LOT TO TAKE IN. I KNOW IT'S LATE IN THE AFTERNOON BUT WE DO WANT TO GET YOUR FEEDBACK ON WHAT YOU'RE THINKING. YOU HAVE BEEN PART OF THESE PRE AND POST AWARD DISCUSSIONS, AND E-MAILS AND WRITTEN CORRESPONDENCE. I WANT TO GET A SENSE OF WHAT YOU'RE THINKING AND WHAT WE'RE DOING WELL AND WHAT MAYBE WE COULD CERTAINLY DO BETTER. LET'S OPEN FOR DISCUSSION. >> I WANTED TO KNOW THINGS YOU DID QUITE SIGNIFICANTLY DECREASING THE NUMBER, WHETHER YOU TRACK THE OUTCOMES OF THAT CHANGE. >> WELL, WE'RE TRACKING THE OUTCOMES. I GUESS WE DON'T HAVE RESULTS. MOST OF THESE GRANTS ARE OVER -- MANY GRANTS ARE TWO TO FIVE-YEAR PROJECTS SO THERE WILL BE A LAG FOR US TO REALLY FIGURE OUT WHAT SORTS OF CHANGES, YOU KNOW, IF ANY, WERE IMPACTED BY THE REDUCTION IN LEVEL OF OVERSIGHT IN GENERAL. >> GREAT QUESTION. >> I WANT TO ASK HAVE YOU EVER THOUGHT ABOUT VOLUNTARY ENHANCED OVERSIGHT? WE TEND TO LOOK NEGATIVELY ON OVERSIGHT, ACTUALLY I THINK SOME PEOPLE MIGHT WELCOME IT. >> YEAH, I MEAN, I HAVE SOME INFORMAL OPINIONS ABOUT THE OVERSIGHT PROCESS, HIGH OVERSIGHT PROCESS. I THINK THERE WAS A REAL CONCERN THAT IMPLEMENTING ON-SITE MONITORING WITH THE HIGHER OVERSIGHT WOULD NECESSARILY DELAY STUDY IMPLEMENTATION. I THINK ACROSS THE BOARDS THAT'S NOT THE CASE. I THINK ONE ASPECT OF OVERSIGHT BE IT IN CLINICAL TRIALS OR OTHER AREAS OF GOVERNMENT ACTIVITIES IS I THINK WHEN THERE ARE MORE PEOPLE PAYING ATTENTION AND THERE ARE, YOU KNOW, TIMELINES FOR PEOPLE TO FOLLOW, AT TIMES THAT SORT OF KEEPS PROJECTS ON THE CONVEYOR BELT, IF YOU WILL, SUCH THAT THEY MOVE ALONG TOO IMPLEMENTATION. I DON'T KNOW IT'S A STRAIGHTFORWARD ANSWER. AND WE'LL DEFINITELY BE COLLECTING INFORMATION ON THAT. WE DO TRACK THE AMOUNT OF TIME IT TAKES FOR PEOPLE TO ACTUALLY START ONCE THEY HAVE GOTTEN THE AWARDS. WE DEFINITELY WILL TRACK THAT. >> I HAVE A LOT OF THOUGHTS ABOUT THIS. I'LL TRY AND KEEP THEM BRIEF. I'VE BEEN DOING THIS FOR A LONG TIME. I THINK IT'S A GREAT IMPROVEMENT, A LOT OF WHAT -- I LOVE THE SARP. I THINK THAT'S A WONDERFUL TOOL. WE'VE RUN INTO A FEW ISSUES WITH THE ACTUAL ELECTRONIC REPORTING, THAT DOESN'T MUCH, IT'S CUMBERSOME, AND IT WOULD BE NICE TO SEE CHANGES TO THAT. IT DOESN'T MATCH. THE ON-SITE MONITORING, I APPRECIATE THE EXTERNAL MONITORING. WE ALWAYS HAVE. WE'VE SEEN JUST A LITTLE BIT SOME DELAYS WITH THAT, AND EVEN OUR ON-SITE MONITORS COME IN AND SAID I DON'T KNOW WHY I'M HERE MONITORING THIS BECAUSE IT DOESN'T LOOK LIKE IT NEEDS MY MONITORING SO THERE'S REFINEMENT THAT NEEDS TO HAPPEN WITH SOME OF THAT. BUT OVERALL I THINK THE CHANGES THAT HAVE HAPPENED HAVE BEEN FOR THE GOOD. AND I DO LIKE -- I'D LIKE TO SAY VOLUNTARY, YOU KNOW, I'D BE THAT PERSON BUT PROBABLY NOT BECAUSE I'M SO BUSINESS. I LIKE BEING TOLD TO DO THIS AS AN INVESTIGATOR. SO OVERALL A GREAT JOB. I GUESS JUST SOME REFINEMENTS IN THE PROCESS AND THE TIMING WITH THINGS WOULD BE APPRECIATED. >> THE ELECTRONIC INTERFACE, IS THAT SOMETHING FOR A SHARE POINT? >> YES. >> I.T. TO -- >> YES. SO, YES. WE DO NOTICE THAT THE -- I'M NOT AN I.T. PERSON BUT DO NOTICE THERE HAVE BEEN I.T. STRUCTURAL CHANGES WITHIN THE NIH THAT HAVE MOVED AND THAT AT TIMES MAKES GREATER COMPLEXITY IN GETTING INFORMATION FROM OUTSIDE OF NIH. >> AND, YEAH, IT'S JUST A HEADS-UP THEY ARE NOT ALWAYS -- I DON'T KNOW, THEY DON'T ALL QUITE ADD UP. SO JUST DATA IN, YOU KNOW, WHAT YOU GET OUT. JUST I DON'T KNOW WHO WE COMMUNICATE WITH IN THERE. I'M ALWAYS COMMUNICATING WITH SOMEONE WHEN WE'RE HAVING TROUBLE WITH THAT. IT'S SOMETHING THAT I'VE SEEN AN EVOLUTION IN THE LAST COUPLE YEARS, IT'S GETTING BETTER BUT IT'S STILL FUNKY. AND JUST DOESN'T MATCH THE WONDERFUL SARP AT THE BEGINNING. THAT'S SUCH A GREAT PROCESS, JUST LIKE TO SEE THE MONITORING A LITTLE TIGHTER. >> VERY HELPFUL. WE'RE CERTAINLY AWARE THIS IS A PROBLEM. AND SO IT'S SOMETHING THAT WE'LL TRACK MORE CAREFULLY. WE'VE HAD SEVERAL ISSUES IN THE LAST CALENDAR YEAR FOR I.T. REASONS, YOU KNOW, WITHIN NIH THAT HAVE BEEN BEYOND OUR CONTROL. >> SHARE POINT UPGRADE, SHARE POINT UPGRADE, YOU KNOW ABOUT UPGRADES, RIGHT? >> YEAH. >> FOLLOWING UP, THE QUESTION ABOUT THE ON-SITE MONITORING, I'M CURIOUS IF YOU THOUGHT, MAYBE I'M SPEAKING BEFORE I CONFER WITH CATHY AND EMMELINE, REVERSE SITE VISIT WHERE MAYBE A BRIEF CALL BETWEEN INVESTIGATOR, ON-SITE MONITORS AND NCCIH STAFF TO SEE WHAT KIND OF ISSUES WERE GOING TO BE ADDRESSED, WHETHER THEY COULD BE RESOLVED ON THE PHONE OR NOT OR WHETHER NEEDED FULL SCALE ON-SITE, WOULD THAT HAVE BEEN HELPFUL? >> THAT WOULD BE APPROPRIATE, YEAH. THAT WOULD HAVE BEEN PERFECTLY APPROPRIATE. >> HOW WE COULD SORT OF TAILOR THIS. >> WE'VE EXPLORED THAT WITH MONITORS. THAT'S REVERSE SITE VISITOR, WE FIND REAL PROBLEMS IN THE FIELD, YOU KNOW, RATHER THAN DOING ANOTHER SITE VISIT TO SEE IF THINGS ARE MODIFIED WE TRY TO DO SOME TUTORIALS AND WORK ON THE PHONE, SORT OF A VIRTUAL VISIT WITH THE STUDY TEAMS >> THE INITIAL SITE VISIT COULD HAVE BEEN THAT, EASILY, IT WOULD HAVE SAFE EVERYBODY A LOT OF TIME AND RESOURCE. >> IT'S A RESOURCE THAT'S LIMITED, FOR US AS WELL, RIGHT. WE CAN ONLY DO SO MANY PER YEAR, CONTRACTS AND LIMITATIONS, MAYBE SOMETHING WE COULD DISCUSS MORE. >> SOMETHING THAT WE'VE TALKED ABOUT WITH THE CONTRACTOR. >> YEAH. >> I THINK CERTAINLY IN THE WORLD OF CLINICAL TRIALS AND CERTAINLY WITH LARGE SCALE STUDIES WITH A HUNDRED SITES, VIRTUAL MONITORING IS BECOMING MUCH MORE COMMON. >> RICK AND THEN BO MIGHT HAVE HAD ANOTHER COMMENT. >> I WANT TO CLARIFY, I DIDN'T MEAN VOLUNTARY ONLY. I MEANT IN ADDITION. [LAUGHTER] >> RIGHT, RIGHT. >> I ALSO AGREE WITH RONNY THAT THINGS HAVE IMPROVED AND YOU GUYS HAVE DONE A GOOD JOB. THIS INSTITUTE IS AMAZING. THE CENTER'S AMAZING. COMING FROM A BASIC SCIENCE BACKGROUND AND THEN TRANSITIONING INTO CLINICAL RESEARCH AT THE BEGINNING OF THE 2000s WHEN THE CENTER WAS TAKING OFF AND GOING THROUGH CAREER DEVELOPMENT AWARDS AND THEN SUCCESSIVE RESEARCH AWARDS, IT WOULD HAVE BEEN HELPFUL IF I HAD A LITTLE MORE TRAINING IN ALL OF THE HOOPS THAT I HAVE TO JUMP THROUGH TO BE SUCCESSFUL, NOT ONLY DO YOU HAVE TO HAVE THE SCIENCE DOWN PAT, THE MESSAGE, THE FIELD, NOW IT'S LIKE EVEN ONCE YOU GET THE AWARD THERE'S THESE THINGS THAT HAVE TO BE MET, MILESTONES THAT HAVE TO BE MET. I TOOK A CLINICAL TRIAL DESIGN AND STATISTICAL ANALYSIS COURSE AT MICHIGAN WHEN I STARTED DOING CLINICAL TRIALS. WE DIDN'T HAVE ANYTHING LIKE THIS AROUND AT THAT TIME BUT IT WOULD REALLY BE HELPFUL IF, YOU KNOW, JUNIOR INVESTIGATORS KNOW IT'S NOT JUST ABOUT GETTING THE AWARD. ONE YOU GET THE AWARD YOU HAVE TO DO ALL THESE OTHER THINGS AS WELL. THAT MIGHT BE HELPFUL. I DON'T KNOW IF YOU HAVE ALL OF THAT. SOMETHING MORE THAN JUST TELECONFERENCES OR LIKE VIDEOS HERE AND THERE, BUT LIKE REALLY GOOD TRAINING FOR JUNIOR RESEARCHERS THAT WANT TO GET INTO THIS TYPE OF FIELD TO DO THIS TYPE OF WORK, I THINK THAT WOULD BE HELPFUL. >> WONDERING -- GOOD POINT, RICK. WONDERING IF THIS IS SOMETHING MAYBE THE INSTITUTION NEEDS TO THINK ABOUT. IT'S MORE THAN JUST UNDERSTANDING CLUSTER RANDOMIZED DESIGN FROM INDIVIDUALLY RANDOMIZED CONTROL TRIAL, APPROPRIATENESS OF DOUBLE BLIND STUDIES, ET CETERA. IS THERE A WAY TO BUILD INTO THE COURSE WHERE MAYBE EVEN NIH STAFF COULD COME AND TALK ABOUT NIH CLINICAL TRIAL OVERSIGHT AND WHAT THAT REALLY MEANS. I THINK SOMEBODY POINTED OUT THIS IS NOT NECESSARILY FOR THE FAINT OF HEART. THERE'S MORE THAT GOES INTO IT THAN JUST RUNNING THE EXPERIMENT FOR OBVIOUS REASONS, WONDERING IF THAT COULD BE BAKED INTO INSTITUTIONAL COURSES WHETHER AT MINNESOTA OR MICHIGAN OR WHEREVER. >> I THINK ALSO JUST BEING ON THE COUNCIL, WHEN I WAS UNDERGOING TRAINING TO BE ON THE COUNCIL THERE'S NOTHING ABOUT TRAINING ON OVERSIGHT, LIKE OCRA, MAYBE I MISSED IT, I DIDN'T SEE ANYTHING. THAT'S A KEY FACTOR AND WHAT GETS FUNDED AND HOW IT GETS DONE. >> BUT THE ISSUE ABOUT EARLY CAREER INVESTIGATORS AND GETTING LAUNCHED IN THE FIELD OF DOING CLINICAL RESEARCH THIS IS NOT YOUR DADDY'S OLDSMOBILE ANYMORE, RIGHT? IT'S DIFFERENT FROM AN R01 20 YEARS AGO, FROM WHAT DR. LAUER SAID, WHERE WE'RE ALL GOING AT THE NIH. IT'S NOT JUST AROUND THE SCIENCE, RIGHT? THE TRIAL DESIGN. IT'S ALL THESE OTHER ASPECTS NOW THAT ARE REQUIRED. AND I THINK THAT'S PART OF TRAINING AT AN INSTITUTIONAL LEVEL, PART OF A POSTDOCTORAL TRAINING, PRE-DOCTORAL, WHATEVER THE RIGHT LEVEL IS, MAYBE ALL OF THE ABOVE. I THINK PARTNERSHIP HERE WHERE WE CAN CERTAINLY HELP WITH EVEN BRINGING PEOPLE TO SPEAK AT THESE COURSES, PROVIDING THE ONLINE RESOURCES WE HAVE, BUT I THINK THE INSTITUTION HAS TO BE OPEN TO ADDING IN THE CURRICULA, NIH DAY OR SOMETHING, I DON'T KNOW WHAT IT IS. YEAH, SORRY. >> I THINK IT WOULD BE EASIER TO WORK WITH YOUR CTSAs THAT WAY, BECAUSE THAT'S WHERE THESE SORTS OF CONVERSATIONS ARE HAPPENING. AND SO THEY ARE TALKING ABOUT THESE SORTS OF THINGS NOW. I KNOW THE UNIVERSITY OF MINNESOTA, OUR Ks ARE GOING THROUGH THAT. I'M SURE THEY ARE AT OTHER INSTITUTIONS BUT HAVING IT MORE STANDARDIZED, NIH COMING IN AND TALKING TO THEM WOULD BE REALLY NICE. >> IS THAT SOMETHING YOU COULD ADD INTO THE CONTENT WHEN YOU GO TO THE CONFERENCE AT THE END OF APRIL? I MEAN, THAT'S AN EASY WAY TO REACH -- >> [OFF MICROPHONE] >> I KNOW WE'RE DOING THIS AS PART OF THE PRISM, MAYBE WENDY COULD TALK ABOUT THIS, I DON'T KNOW IF WE PUT IN A PART OF THAT SORT OF TRAINING, PRISM IS NOW GOING THIS ROADSHOW, VARIOUS CONFERENCES TO TALK ABOUT PRAGMATIC RESEARCH, SOMETHING TO THINK ABOUT AS WE STARTING TO DEVELOP PROGRAMS THAT ARE BECOMING VISIBLE, SOMETHING WE'LL CONTINUE TO KEEP DOING, WHETHER WE CAN BUILD IN WHAT RICK JUST TALKED ABOUT, THE IDEA THE ROLE NIH PLAYS IN OVERSIGHT. >> I THINK WHEN WE STARTED DEVELOPING THOSE SPECIFIC FUNDING OPPORTUNITY ANNOUNCEMENTS WE CAPITALIZED ON THE INTEGRATIVE -- INTERNATIONAL CONGRESS FOR COMPLEMENTARY AND INTEGRATIVE MEDICINE MEETINGS. WE HAD A NUMBER OF WORKSHOPS, THIS WAS LIKE A ONE-TIME SHOT. I THINK PERHAPS WE NEED TO HAVE SOMETHING A LITTLE MORE SUSTAINED THAT WOULD ACTUALLY DELVE INTO MORE DETAIL, ESPECIALLY IN THE CONTEXT OF THE OVERSIGHT. GOOD IDEA, SOMETHING FOR US TO CHEW ON. >> I JUST -- ONE FINAL COMMENT ABOUT HOW MUCH THE CLINICAL TRIALS ENTERPRISE HAS CHANGED IN 10 OR 15 YEARS, THE LIST OF REGULATORY REQUIREMENTS IT'S NOT JUST THE NIH. SO CERTAINLY OUR COLLEAGUES AT FDA, OHRP, YOU KNOW, THERE ARE A LOT OF US IN THE MIX. AND I THINK TRYING TO PERHAPS NOT EVEN JUST HAVE NIH DAY BUT ASKING US TO IDENTIFY OUR COLLEAGUES AS SISTER AGENCIES THAT CAN PROVIDE SOME INFORMATION AND TRAINING FOR JUNIOR INVESTIGATORS WOULD BE TERRIFIC. >> LAST THING IS A CLINICAL TRIAL IS NOT A CLINICAL TRIAL IS NOT A CLINICAL TRIAL. SEVERAL OF US DO MECHANISTIC STUDIES IN HUMANS THAT INVOLVE INTERVENTIONS THAT ARE TRIAL-LIKE, BUT IT'S NOT GOT EFFICACY AS AN ENDPOINT, AND SOME OF THE DOCUMENTS IT'S HARD TO FIT -- LIKE ON clinicaltrials.gov IT'S A BEAR TO GET THE BASIC SCIENCE TYPE OUTCOMES WHICH WERE OUR PRIMARY OUTCOMES IN THE FORMAT THE AGENCY WANTS IT. TO HELP WITH THAT KIND OF STUFF WOULD BE NICE OR LIKE SOMETHING WHERE EVEN LIKE WITH REPORTING LIKE WITH ACCRUAL REPORTING, ELECTRONIC REPORTING THAT RONNY WAS SAYING, I HAD MULTIPLE TYPES OF PEOPLE IN MY STUDIES WITH DIFFERENT AIMS AND DIFFERENT TIMELINES AND SO LIKE HOW DO YOU JUDGE RECRUITMENT? SO ANYWAY THAT I FELT DIFFICULT TO LIKE REPORT BACK AND SAY ACCURATELY HOW MANY PEOPLE I RANDOMIZED IN HEALTHY CONTROLS, THEY WEREN'T GETTING INTERVENTION, REALLY HARD FOR ME TO JUST GIVE YOU WHAT YOU WANTED. SO I HAD TROUBLE WITH THAT ON MY LAST GRANT. >> I JUST WANT TO ECHO THAT POINT REAL QUICK. I THINK ALL THESE SUGGESTIONS ARE GREAT. MY FIRST NCCIH GRANT, I WAS TOLD IT WAS A CLINICAL TRIAL, ALL THIS TIME WHEN THE REGULATORY PROCESSES WERE CHANGING, LIKE I WAS JUST LIKE OVERWHELMED, EVEN IF IT'S A SENIOR INVESTIGATOR, IF IT IS FIRST PROJECT THAT'S GOING TO BE TREATED AS A CLINICAL TRIAL, I THINK THEY NEED ADDITIONAL EDUCATION AND WARNING AND MAYBE EVEN WHEN THEY ARE SUBMITTING IT, YOU KNOW, IF THAT'S WHAT'S GOING TO HAPPEN AS YOUR FIRST ONE, LIKE YOU SAY, IT'S NOT FOR THE FAINT OF HEART. YOU MIGHT THINK A LITTLE BIT MORE ABOUT WHAT YOU'RE GOING TO PLAN BUT THEN GETTING IT ON THE BACK END YOU GET A GREAT REVIEW SCORE AND THEN YOU HEAR THERE'S ALL THESE ADDITIONAL THINGS YOU DIDN'T KNOW ABOUT CAN BE PRETTY DAUNTING SO WARNING PEOPLE AND GIVING THEM ASSISTANCE. >> I'M THINKING PRACTICALLY ABOUT THIS, DIGGING IN THE WEEDS, WOULD THAT BE SOMETHING THAT WOULD BE PART OF JUST-IN-TIME WHERE, YOU KNOW, IN ADDITION TO THE STANDARD FORM LETTER FROM NIH, WE'RE NOT UNIQUE, EVERY INSTITUTE IS GOING IN THIS DIRECTION BECAUSE OF WHAT YOU HEARD FROM DR. LAUER, WOULD IT BE HELPFUL TO SAY -- BY THE WAY, OVER THE NEXT THREE TO FOUR MONTHS YOU'RE GOING TO NEED THE FOLLOWING, WOULD THAT BE USEFUL AND JUST-IN-TIME -- I WAS TRYING TO THINK OF WAYS -- HOW DOES THAT SOUND? I DON'T KNOW IF LINDA IS HERE, LINDA RICH. MAYBE THAT'S SOMETHING, LINDA, WE COULD THINK ABOUT. IT ALREADY IS THERE? OKAY. I GUESS I THOUGHT WE DID DO SOMETHING LIKE THAT. MAYBE WE NEED TO BOLD IT OR SOMETHING. [LAUGHTER] >> (OFF MIC.). >> OKAY. BUT I GUESS IT'S NOT -- MAKE IT MORE SALIENT. >> MAYBE YOU CAN GIVE THEM SOMEBODY TO DO IT FOR THEM. THAT WOULD BE GOOD. [LAUGHTER] >> WHAT ARE YOU SUGGESTING? >> NOT QUITE. IT'S LIKE THEY NEED A BUDDY. WE DO GET OVERWHLMED. YES, ALL THE DOCUMENTS WE GET THROWN AT US, AND NOW THAT WE'RE RESPONDING TO EVERYTHING, LIKE IT'S A LOT. THIS IS ABOUT DOING SOMETHING. IT SHOULDN'T TAKE THAT LONG TO TRY AND SORT OUT, YOU KNOW, PUNCH IN A FEW NUMBERS TO GIVE YOU YOUR DATA. THIS IS ABOUT THERE MUST BE A TIP FOR HOW TO DO IT, GETTING ON THE PHONE WITH SOMEONE AND JUST DOING IT. LIKE I THINK THINGS GET LOST OR MAYBE THERE'S A LITTLE VIDEO. THIS IS HOW YOU DO IT, YOU KNOW. FILL OUT YOUR REPORTING. >> CHANGE IS HARD. >> I DON'T WANT ANY MORE THINGS IN PRINT. I'M JUST SAYING. >> REACHING OUT AND TOUCHING SOMEONE IS THE BETTER WAY. THESE ARE GOOD SUGGESTIONS. I THINK BACK TO WHEN WE TRANSITIONED TO GRANTS.GOV, CHALLENGES GOING TO THAT. >> UH-HUH, SUBMITTING GRANTS. >> THERE'S NO PERFECT SOLUTION BUT I'M HEARING WAYS OF SORTING GIVING YOU WARNING SIGNS ABOUT WHAT TO EXPECT AND WHAT IT MEANS TO GET A CLINICAL GRANT THROUGH NIH AND HOW WE CAN DO THAT BETTER, I'M HEARING THAT LOUD AND CLEAR. THIS IS GOOD INFORMATION. IT'S A BLIND SPOT FOR US. >> SO, I'VE BEEN HEARING COMMENTS ABOUT PEOPLE NOT BEING HAPPY ABOUT ONCE YOU GET FUNDED, AND THEN HAVING TO ANSWER A LOT OF QUESTIONS ABOUT THE DESIGN OF THE STUDY, CONTROL GROUPS, MAYBE STATISTICAL ANALYSIS. AND, YOU KNOW, THERE'S KIND OF THIS BACK AND FORTH SOMETIMES THAT GETS INVESTIGATORS IRRITATED, YOU KNOW, I GOT A GOOD SCORE, THIS IS MY STUDY, I'D LIKE TO DO IT THE WAY I WANT TO DO IT. IS THERE A SENSE AMONG YOU THAT THE AMOUNT OF OVERSIGHT IN THE SENSE OF TRYING TO IMPROVE THE STUDY POST AWARD OR PRE-AWARD IS APPROPRIATE, TOO MUCH, WITH THE UNDERSTANDING THERE'S ALWAYS THE OTHER SITUATION WOULD BE SAY REVISE AND RESUBMIT, RIGHT? SO ANY THOUGHTS ABOUT THAT? >> I THINK THE ONLY FRUSTRATION IN MY EXPERIENCE IS WHEN AN EXTERNAL REVIEW COMES IN, THINGS NEED TO BE DONE DIFFERENTLY BUT THERE'S NO ADJUSTMENTS IN THE BUDGET. THAT'S TOUGH. AND THEN, YOU KNOW, YOU TRY TO ARGUE FOR THE SENSIBILITY, FOR EXAMPLE, OF ADDING MORE THINGS AND THEN OF COURSE NOT HAVING POWER BECAUSE YOU'VE DONE SOME THINGS. THOSE ARE THE THINGS THAT I THINK ARE FRUSTRATING. >> AND I SECOND THAT. OVERALL, I LIKE THE DIALOGUE THAT WE'VE HAD. I THINK THE DIALOGUE HAS MADE OUR STUDIES BETTER. IT HAS. THAT'S BEEN FANTASTIC. BUT NOT TAKING INTO ACCOUNT SOME OF THE CHANGES TO THE BUDGET AND SOME OF THEM ARE SIGNIFICANT. THEY REQUIRE A LOT MORE RESOURCE. THERE DOESN'T SEEM TO BE LATITUDE THAT WE'RE AWARE OF. WHAT CAN WE DO ABOUT THAT? OVERALL, I DON'T KNOW WHETHER I'VE ENJOYED THE PROCESS, THAT MIGHT BE OVERSTATING IT A LITTLE BIT. BUT IT HAS MADE OUR RESEARCH BETTER. >> REACHING OUT TO SEE WHETHER ANYONE ON THE VIDEO CONFERENCE, DR. TIMERMAN, DR. YAY OR DR. HENSEL, HAD ANY COMMENTS THEY WANT TO RAISE? >> NO, THANK YOU. >> DR. TIMERMAN, YOU'RE ON MUTE. WE CAN'T HEAR YOU. WE CAN SEE YOU. YOU NEED TO UNMUTE. YOU'RE GOOD NOW. >> SO I'M HERE. YEAH, SO I'M LISTENING WITH GREAT INTEREST, THE CLINICAL TRIALS PART OF PROJECTS, YOU KNOW. I HAVE BEEN DOING ALWAYS THE BASIC RESEARCH SO I DON'T HAVE MUCH EXPERIENCE WORKING WITH CLINICAL TRIALS. BUT IF I COULD SHARE SOME OF MY OWN EXPERIENCES WITH THE NIH PROJECT FROM THE FOGARTY CENTER, THAT ALSO WAS A BRAND-NEW TYPE OF PROJECT, WE DIDN'T HAVE MUCH PRECEDENT HOW TO DO THINGS WITH INTELLECTUAL PROPERTY RIGHTS AND EQUITABLE SHARING AND BENEFITS WITH, YOU KNOW, OTHER COUNTRIES. SO WHAT WAS VERY POSITIVE WAS TO GET TOGETHER WITH THE OTHER P.I.s OF OTHER ICBG PROJECTS AND THEN WE FIGURED THINGS OUT WITH THE HELP OF THE NIH, OF THE FOGARTY CENTER. SO, LISTENING TO WHAT YOU ARE SAYING PERHAPS THE P.I.s WHO HAVE THE CLINICAL TRIALS, NCCIH WOULD HAVE A MECHANISM OF GETTING TOGETHER ONCE A YEAR AND SHARING THEIR EXPERIENCES AND HAVING THIS BUDDY TYPE OF SUPPORT SYSTEM ALONG WITH THE NIH OFFICIAL. SO I THINK THAT COULD BE VERY HELPFUL. BECAUSE THERE ARE MANY THINGS THAT ARE NEW, AND AS A RESEARCHER, ESPECIALLY MORE JUNIOR INVESTIGATORS, YOU KNOW, PEOPLE COULD SAVE A LOT OF TIME NOT TRYING TO REINVENT THE WHEEL. SO PERHAPS THE NIH WOULD HAVE SOME TYPE OF FORUM ONCE A YEAR FOR THE P.I.s TO GET TOGETHER AND KIND OF COMPARE NOTES. >> GOOD THOUGHT. >> I THINK IT'S A MODEL THAT WE TYPICALLY USE FOR OUR LARGER COOPERATIVE AGREEMENT GROUPS, SO FOR EXAMPLE THE NIH COLLABORATORY WHERE WE HAVE A NUMBER OF INVESTIGATORS FROM DISPARATE COMMUNITIES THAT ARE TRYING OUT NEW METHODS WITH A NUMBER OF UNCERTAINTIES. AND SO WE'VE PUT TOGETHER WORKING GROUPS OF SUBJECT MATTER EXPERTS IN PARTICULAR AREAS, AND THEN BRING THEM TOGETHER WITH THE STUDY TEAMS, FOR THEM TO WORK OUT DIFFICULT PROBLEMS. AND SO AS A MODEL, IT'S WORKED REALLY WELL. WE HAVE WONDERFUL COLLEGIAL CONVERSATIONS AMONGST THE INVESTIGATORS, AND OUR NIH EXPERTS, WHERE WE DO WORK THROUGH A LOT OF PROBLEMS. AGAIN, THESE TEND -- WE TEND TO IT'S USUALLY EMBEDDED INTO FOAs AND COORDINATING CENTERS, WHETHER THERE'S A SIMILAR STRATEGY WE MIGHT INVENT ON A SMALLER SCALE FOR INTERVENTION COMMUNITIES OR INVESTIGATORS AT A CERTAIN LEVEL IN THEIR CAREER PATH IS PROBABLY SOMETHING WE COULD THINK ABOUT. >> THE WEBINAR, I DON'T KNOW, THERE'S GOT TO BE A WAY. IT'S THE COMMON THEME WE'RE HEARING FROM THE COUNCIL ABOUT SORT OF KNOWING WHAT YOU'RE GETTING INTO I GUESS IS ONE WAY TO SAY IT. AND KNOWING THAT EARLY IS POSSIBLE. AND MAYBE EVEN EARLY IN YOUR CAREER IS POSSIBLE BECAUSE I THINK BEFORE YOU DECIDE TO GO INTO CLIP CAL RESEARCH. -- CLINICAL RESEARCH. I DON'T KNOW WHETHER YOU WOULD HAVE TAKEN THE LEAP, RICHARD OR TODD. WE ALL HAVE THE BEST INTENTIONS REPRODUCING RIGOR AND REPRODUCIBILITY, IT'S NOT DONE AS A CAPRICIOUS THING. IT'S MORE DONE BECAUSE OF WHAT WE'RE TRYING TO ACCOMPLISH. BUT THESE ARE EXCELLENT SUGGESTION AND I THINK WE'VE TAKEN A LOT -- WE HAVE SOME VERY GOOD SUGGESTIONS WE WILL FOLLOW UP ON. ARE THERE ANY OTHER THOUGHTS? THIS HAS BEEN A VERY RICH DISCUSSION. I APPRECIATE IT. YEAH, BO? >> I WANT TO POINT OUT HOW MUCH MORE DIFFICULT IT WOULD BE FOR A COMPLEMENTARY AND INTEGRATIVE HEALTH INSTITUTION TO DO THIS TYPE OF RESEARCH AND IMPACT THAT MIGHT HAVE ON NEW STRATEGIC PLANS. >> YES, YES, YES. >> A FINAL REACH OUT, DR. HENSEL, DR. YAY, ANY COMMENTS OR QUESTIONS? >> IT'S GLORIA. I DON'T THINK I HAVE ANYTHING SUBSTANTIAL TO ADD BUT I WILL SAY JUST AS A CLINICAL -- SOMEBODY WHO DOES CLINICAL TRIALS AND WHO, YOU KNOW, DURING THOSE TIMES 80 TO 90% ENHANCED FELL INTO THE CATEGORY, ON-SITE MONITORING, AND EVEN THOUGH I DON'T FEEL LIKE THERE WAS ANYTHING, LIKE, EARTH SHATTERING, YES, NEEDED, BUT I APPRECIATE THE WHOLE DISCUSSION AND HOW EVERYTHING WAS LAID OUT IN TERMS OF THE RATIONALE BEHIND THIS WHOLE PROCESS AND I APPRECIATE THE THOUGHTFULNESS, I'M REPEATING, HOW EVERYONE HAS THE BEST INTENTIONS IN TERMS OF GOING FORWARD AND I THINK IF THERE WAS A WAY TO REALLY GIVE THE INFORMATION TO THE INVESTIGATORS, EARLY ON, AND PARTICULARLY JUST THAT RATIONALE I THINK WOULD HELP THAT -- HELP EVERYONE BE ON THE SAME PAGE REGARDING THIS PROCESS. >> THANK YOU. >> THIS IS KIMBY. THE ONLY COMMENT I WOULD MAKE IS JUST THAT I AGREE WITH THE COMMENTS EARLIER ABOUT THE COMPLEXITY OF REALLY UNDERSTANDING THE NUANCES OF ALL THE DIFFERENT MECHANISMS, AND HAVING SOME BETTER SORTS OF TRAINING OR RESOURCES AVAILABLE TO TRY TO CLARIFY THAT, AND THAT, TO ME, SORT OF FEEDS IN WITH THE INCREASED OVERSIGHT ON CERTAIN PROJECTS AND THAT IS THAT IT'S FOR NOVICE INVESTIGATORS I THINK IT'S VERY HARD TO TRY TO SCALE THAT LEARNING CURVE BECAUSE THERE IS SO MUCH COMPLEXITY THERE. I AGREE WITH THE COMMENTS AND THE DISCUSSION THAT SOME WEBINARS OR WORKSHOPS OR A GUIDE, LIKE A PUBLISHABLE GUIDE, THAT COULD BE EVEN PRE-READING FOR SOME OF THE WORKSHOPS, I THINK WOULD BE VERY HELPFUL. >> GREAT. THANK YOU. WE'RE HEARING A COMMON THEME THAT WE WILL DEFINITELY FOLLOW UP WITH. AND NOW WE HAVE ZOOM AND WEBEX, WE CAN SEE EVERYBODY IN THE WORLD, I GUESS. SO THERE'S OPPORTUNITIES TO DO THIS AT A MORE CENTRALIZED WAY, DISSEMINATE TO A LARGE COMMUNITY. ANY OTHER -- WE HAVE TO GO TO PUBLIC COMMENT. OKAY. WE'RE BEING TOLD BY OUR -- >> I WANT TO SAY THANK YOU. I THINK THIS SESSION, IN MY VIEW, ACCOMPLISHED WHAT WE WERE HOPING WAS GOING TO HAPPEN. I FEEL WE TALKED OPENLY ABOUT THIS. I THOUGHT THERE WERE EXCELLENT PRESENTATIONS, ALSO EXCELLENT QUESTIONS, EXCELLENT COMMENTS. I HOPE YOU ALL CAN BE OUR EARS TO THE EXTERNAL RESEARCH COMMUNITY AND OUR FEEDBACK TO US. THIS IS WHAT WE WANT YOU AS A COUNCIL, HELP US TO -- AND TALK TO YOUR COLLEAGUES. IF BY TALKING WITH YOUR COLLEAGUES YOU GET OTHER TYPES OF FEEDBACK ABOUT THIS, PLEASE GET BACK TO US, NOT JUST TODAY BUT WE WANT TO HEAR. IT'S IMPORTANT. THIS IS HOW YOU CAN HELP US. >> OKAY. THANK YOU VERY MUCH, EVERYONE. WE'RE NOW GOING TO HAVE THE PUBLIC COMMENT SESSION FOR THE COUNCIL MEETING, AND WE HAVE TWO PEOPLE WHO HAVE REQUESTED TO SPEAK. FIRST IS MISS ASDA GANDERA WITH THE COSMO INTEL, INC. ORGANIZATION. YOU HAVE FIVE MINUTES. >> HELLO, I'M FROM COSMO CORPORATION, I'M SO HAPPY I'M HERE AND THE SESSION WAS VERY INFORMATIVE FOR ME BECAUSE I'M GOING TO APPLY FOR MY RESEARCH, FOR MY FUTURE RESEARCH, I'M SO HAPPY THAT I HAVE THIS MUCH INFORMATION ON WHAT I AM GOING TO DO. I'M JUST GIVING SHORT BRIEF INFORMATION ABOUT WHAT IS (INDISCERNIBLE), A TYPE OF COMPLEMENTARY THERAPY WITH MYSTIC PERSPECTIVE AND IS SUBCATEGORY OF MYSTICISM, BASED ON THE THEORY OF CONSCIOUS BOND, A LINK BETWEEN CONSCIOUSNESS AND CONS THE CITY WENT -- MIND BEGIN TO CORRECT, REPAIR, FIX THE BODY, PERFORMANCE OF THE PSYCHE AND OTHER PARTS OF THE MIND AS WELL. THEREAFTER HEALING RECOVERY TAKES PLACE. IN THIS BRANCH OF THERAPY THE PATIENT IS CONNECTED TO THE CCM, INTELLIGENCE AND AWARENESS GOVERNING THE UNIVERSE. WHILE THE PATIENT IS UNDERGOING TREATMENT HE MIGHT FEEL WARMNESS, COLDNESS, PAIN, TINGLING, CONVULSION, SEIZURE, ET CETERA, WHICH REVEALS CONFLICTING PARTS OF THE BODY THUS REMOVING THE SYMPTOMS AND LEADING TO TREATMENT OF THE DISEASE OR DYSFUNCTIONAL PARTS. THIS THERAPY IS CALLED (INDISCERNIBLE), LITERAL TRANSLATION ULTRA THERAPY, BECAUSE IT COMES FROM A TYPE OF VIEWPOINT CALLED ULTRA HOLISTIC VIEWPOINT, ACCORDING TO THIS PERSPECTIVE MAN'S EXISTENCE IS SEEN AS VAST AS THE UNIVERSE, MORE THAN A SET OF FLESH AND BONES. THIS VIEWPOINT MAN IS A COLLECTION OF PHYSICAL, PSYCHOLOGICAL, MENTAL, AND OTHER NUMEROUS BODIES INCLUDING VARIOUS ENERGY TRANSFORMERS, CHAKRA, FIELDS OF THE BODY, CELLULAR CONSCIOUSNESS, ENDLESS UNIDENTIFIED PARTS. DURING THE THERAPY TIME PATIENTS USING THIS CONNECTION WITH CCM, EVERY PART OF THE HUMAN EXISTENCE IS SCANNED AND THEY EXAMINE WHICH THEN CONTINUES TO TREAT THE INLETS ACCORDING TO DISCRETION, THIS CONFLICTING PARTS ARE IDENTIFIED ACCORDINGLY AND PRIORITIZED FOR ANALYSIS AND TREATMENT BY THE CCM. THANK YOU FOR LISTENING. I'M HERE FOR ANY COMMENTS OR QUESTIONS. THANK YOU. >> (OFF MIC.). >> GOOD AFTERNOON. I TALK ABOUT THE (INDISCERNIBLE) ALSO. I'M (INDISCERNIBLE), PSYCHOLOGIST, AND RESEARCHER, I HAVE RESEARCH FROM TEN YEARS AGO ABOUT A NEW SCIENCE BY COSMIS CONSCIOUSNESS BASE, FOUNDED BY (INDISCERNIBLE) FROM IRAN. PLEASE INFORM IT'S THE FIRST TIME IN THE SCIENCE WORLD HISTORY THAT HUMAN CAN USE THE NETWORK AND USE ITS BENEFITS, BY THE SCIENTIFIC THEORY THAT IS REPEATABLE AND TESTABLE. TWO OF THE SUBCATEGORIES ARE (INDISCERNIBLE) TWO COMPLEMENTARY AND ALTERNATIVE MEDICINE IN IRAN, FREE FOR EVERYONE, AND THEY DON'T NEED TO ANY DRUGS OR PILLS. DISORDERS COULD BE CURED IN THIS METHOD. OUR EXPERIENCE IS ABOUT 70% RESULT POSITIVE RESULT. RIGHT NOW ONE MILLION PEOPLE IN IRAN USE THIS MEDICINE. WE CAN PROVE THIS CLAIM IN A SHORT TIME. AND I (INDISCERNIBLE) HOW MANY SCIENTIFIC THEORIES AND ONE OF THEM, ONE OF THE SCIENTIFIC THEORIES ABOUT THE NEW VIRUSES, IF IN A PERIOD OF TIME HUMAN DON'T RESPECT THE EARTH AND START TO DESTROY IT EARTH PLANET ECOSYSTEM TO DIFFERENCE ITSELF RELEASE NEW VIRUSES, AND MAYBE THIS RECENT CORONAVIRUS MAYBE THIS IS KIND OF THE STORY. WE WILL HAVE VIRUSES IN FUTURE YEARS, UNFORTUNATELY PEOPLE AND SCIENTISTS HAVEN'T ANY INFORMATION ABOUT THAT AND THEY DON'T KNOW THE SOLUTION OF THE PROBLEM. ACCORDING TO DR. (INDISCERNIBLE) PEOPLE CAN USE THE CONSCIOUSNESS FOR SOLUTION AND CURE THESE VIRUSES. NUMBER ONE, USE SPECIAL CONNECTION, NUMBER TWO USE THE THERMODYNAMIC CONNECTION, NUMBER THREE THE NETWORK TO CHANGE THE BEHAVIOR OF HUMAN TO BE BETTER RESIDENTS IN EARTH. AND NUMBER FOUR, ACCORDING TO THEORY OF CONSCIOUSNESS FIELD AND CONSCIOUSNESS IMMUNITY AND ACCORDING TO THEORY OF PEACE A MAN THAT FINDS OUT THE RULES OF EXISTENCE SUCH AS RULES OF PEACE AND SYNCHRONIZED BY THEM AND ECOSYSTEM IN THIS REAL IF MAN IS CONTAMINATED BY VIRUSES IN HIS BODY, THE VIRUSES DON'T ATTACK HIM. AND WILL LEAVE WITH PEACE IN THAT BODY. IN A SPECIFIC EQUATION IN FUTURE, AFTER A VIRUS (INDISCERNIBLE) ONLY THE PEOPLE WILL BE ALIVE THAT THEY HAVE CONSCIOUSNESS IMMUNITY. THANK YOU. >> FINAL COMMENTS? >> THANK YOU FOR BEING HERE. THOSE THAT WERE ON VIDEOCAST, I THOUGHT IT WAS A VERY INTERESTING DAY. AND I WISH YOU A SAFE TRIP HOME. LOOKING FORWARD TO SEEING YOU NEXT TIME. >> THANK YOU EVERYONE. THIS CONCLUDES THE COUNCIL MEETING.