>> WELCOME TO SESSION TO WITH THE REG LATTERY ASPECTS OF CLINICAL RESEARCH. WE HAVE A FULL MORNING OF TALKING ABOUT IRBs, THEIR SUBJECT COLLECTION AND WE WILL HEAR FROM A PANEL WHO HAVE DIFFERENT ROLES IN THE CONDUCT OF RESEARCH AND WE'LL HEAR FROM THEM ABOUT THE ETHICAL ISSUES THEY FACE. BEFORE WE START, I WANT TO MAKE SURE THAT PEOPLE KNOW THAT TODAY, I SHOULD HAVE ANNOUNCED THIS LAST WEEK, BUT TODAY AT NOON IN THIS SAME AUDITORIUM IS AN ETHICS GRAND ROUNDS AND LITTLE, THE TITLE IS WHO SHOULD BE ABLE TO ENROLL IN A PHASE 1 CLINICAL TRIAL. IT'S A UNIQUE ETHICS GRAND ROUNDS BECAUSE THE CONSULT REQUEST WAS BROUGHT TO US BY A RESEARCH PARTICIPANT HIMSELF AND HE WILL BE PART OF THE ETHICS GRAND ROUNDS THIS AFTERNOON. SO IF YOU CAN STAY, PLEASE DO, IF YOU CAN'T, IT'S AVAILABLE ON VIDEOCAST SO YOU CAN WATCH IT AT SOME OTHER TIME. SO TO START US OFF THIS MORNING, WE HAVE SARAH HALL WHO WILL TALK ABOUT THE PURPOSE, FUNCTION OF IRBs, SUCCESSES AND CURRENT CHALLENGES, SARAH IS AN NIH CHAIR, HERE AT THE INTRA MURAL PROGRAM AND ALSO THE HEAD OF THE BI ONY ETHICS CORE FOR THE NHGRI, INTRA MURAL PROGRAM AND ASSOCIATE INVESTIGATOR AND NHGRI AND A FACULTY MEMBER IN THE CLINICAL CENTER AND WE ARE VERY GRATEFUL TO SARAH FOR BEING HERE THIS MORNING: THANK YOU. GOOD MORNING AND THANK TO YOU EVERYBODY DOING REMOTE. I UNDERSTAND WE A LOT OF PARTICIPATION ONLINE AND IT'S WONDERFUL WE CAN ALL BE HERE TOGETHER IN 1 WAY OR ANOTHER. SO AS CHRISTINE MENTIONED, I WILL TALK ABOUT IRBs, INSTITUTIONAL REVIEW BOARDS WITH THE PURPOSES, IN GENERAL HOW THEY FUNCTION AND SOME PROPOSALS THAT HAVE BEEN MADE TO IMPROVE UPON THE STRUCTURE AND FUNCTION AND PERFORMANCE OF IRBs. IMPORTANT DISCLAIMER, THIS IS JUST ME TALKING AND MY VIEW IS NOT NECESSARILY THOSE OF THE FEDERAL GOVERNMENT AGENCIES THAT EMPLOY ME. BEING AN IRB CHAIR SOMETIMES REQUIRES HAVING A THICK SKIN. YOU ARE SOMETIMES THE FOCUS OF THE BRUNT OF FRUSTRATION THAT INVESTIGATORS AND OTHERS EXPERIENCE BECAUSE OF THE DELAYS ASSOCIATED WITH ETHICAL OVERSIGHT AND BECAUSE OF THE CHANGES THAT IRBs SOMETIMES REQUIRE. SO LAST YEAR, WHEN I WAS WORKING ON THIS LECTURE FOR THE FIRST TIME, I WASN'T SURPRISED TO COME UPON SOMETHING LIKE THE FOLLOWING IN A NEWSPAPER, A STATEMENT BY STEVEN PINKER THAT SAYS: I WAS QUITE SURPRISED TO READ ON AND DISCOVER THAT HE WASN'T TALKING ABOUT IRBS BUT THE FIELD OF BIOLOGICS PARTICULARLY, HE SAID OF COURSE, INDIVIDUALS MUST BE PROTECT FRIDAY IDENTIFIABLE HARM BUT WE ALREADY HAVE AMPLE SAFE GUARDS FOR THE SAFETY AND INFORMED CONSENT OF PATIENTS AND RESEARCH. HIS POINT WAS THAT IRBs ARE DOING GOOD JOB AND IT WAS A PART OF A TWIST ON THE WAY THAT THIS KIND OF ARGUMENT USUALLY GOES, IT WASN'T NECESSARILY CONVINCED IN AS CHRISTINE MENTIONED, I WEAR MULTIPLE HATS SO I DIDN'T LIKE THE THOUGHT THAT EVERYONE ELSE WAS DOING BUT REFRESHING TO HEAR THAT MAYBE IRBs ARE FUNCTIONING SUFFICIENTLY BUT THAT RAISES THE QUESTION, DOES IRB REVIEW WORK AND SOME HAVE SAID THAT WE REALLY DON'T KNOW IF IT'S SUCCEEDING AT THE SPECIFIC TASK OF PROTECTING HUMAN PARTICIPANTS IN RESEARCH. THERE HAVE BEEN NO CONTROL TRIALS IN DIFFERENT PHASE OF IRBs, AND THERE'S VARIABLES OF THAT BUT WE DON'T KNOW IF THAT TRANSLATES INTO THE KINDS OF PROTECTION THAT WE WOULD WANT TO SEE. THERE'S NO UNDERLYING THEORY OR FRAMEWORK OF WHAT IT MEANS TO BE A GOOD QUALITY REVIEWER AND EFFECTIVE REVIEW. THERE'S A LACK OF LONGITUDINAL ASSESSMENT AND THERE'S BEEN LITTLE RESEARCH WITH KEY STEAK HOLDERS, IN OTHER WORDS WITH RESEARCH PARTICIPANTS, THERE HAVE BEEN SOME STUDIES OF IRBs OF BOARDS THEMSELVES ABOUTLET PROCESS, SO THIS WAS BASED ON A REVIEW OF 198 IMPERICAL STUDIES ABOUT IRB REVIEW THAT WAS PUBLISHED LAST YEAR. SO, INTERESTING, WHY ARE WE DOING THIS AT ALL? WELL SOME HAVE ARGUED AND HAVE ARGUED FOR QUITE SOMETIME THAT THE EXISTENCE OF IRBs HAS IMPORTANTLY CHANGED THE CULTURE IN WAYS THAT MATTER. SO EDGAR AND ROTHMAN ARGUED THAT: WELL THAT'S CERTAINLY SOMETHING AND THAT'S IMPORTANT TO OBSERVE A CULTURAL SHIFT THAT IMPROVES THE WELFARE OF HUMAN SUBJECTS IN RESEARCH. I KNEW IRBs HAD MADE IT WHEN I DISCOVERED THAT THEY HAD BEEN INCORPORATED ON VIRAL MEANS ON THE INTERNET SO THIS IS 1 THAT MAYBE YOU SEE IN A CLASSIC INTERNATIONAL BETWEEN BAT MAN AND ROBIN WHERE HE WAS SAYING, THE IRB WAS TAKING TOO LONG SO I DID THE SURVEY WALLET APPROVAL AND BAD MAN HEARD THAT WRONG, HE SAID YOU CAN'T PASS THAT WITHOUT THE IRB. SOME PEOPLE HAVE ATTEMPTED TO REALLY PINPOINT WHAT THE SPECIFIC CHALLENGES ARE THAT FACE IRBs AND ZEEK EMANUEL AND SOME OF OUR COLLEAGUES AT THE NIH BOILED IT DOWN TO 3 CATEGORIES OF ISSUES, THEY HIGHLIGHTED STRUCTURAL PROBLEMS THAT LEAD TO REPETITIVE IRB REVIEW, INCONS CYSTENCY--AND TO THEE SECOND SEEDURAL PROBLEMS THAT IRB REVIEW IS OVERLY TIME CONSUMING, THERE IS INADEQUATE GUIDANCE AND TOO MUCH PICKING OF PERFORMANCE DETAIL ABOUT BROADER ETHICAL CONCERNS THAT SHOULD TAKE UP MORE OF OUR TIME FOR THE RISKIER KINDS OF RESEARCH FOR EXAMPLE. AND THIRD THEY FLAG THE CHALLENGE OF AN ABSENCE OF DATA TO BE ABLE TO COMPARE PERFORMANCE AND ASSESS HOW IRBs ARE DOING. SO WITH THAT, INTRODUCTION, LET ME JUST SAY A FEW WORDS ABOUT WHAT I WOULD LIKE TO ACCOMPLISH TODAY. I WANT TO GIVE A VERY BRIEF HISTORY AND BACKGROUND OF INSTITUTIONAL REVIEW BOARDS AND TALK ABOUT HOW THEY FUNCTION WITH A PARTICULAR FOCUS ON THE NIH INTRA MURAL RESEARCH PROGRAM AND OUR PARTICULAR SET OF POLICIES AND PROCEDURES. SO THIS WILL INCLUDE HOW THEY'RE MADE UP, HOW THEY REVIEW PROTOCOLS, WHAT THE PROCESSES LOOK LIKE. AND I DO WANT TO FOCUS ON A COUPLE OF PROPOSALS THAT HAVE BEEN MADE FOR IMPROVING IRB FUNCTION AND IN PARTICULAR LOOKING AT A MOVEMENT TOWARD ACCREDITATION AND WHAT HAS HAS ACCOMPLISHED AND A SHIFT SHIFT TOWARDS THE CENTRALIZATION OF IRB REVIEW FOR MULTICENTER RESEARCH AND THEN STILL AT THE END OF THE DAY, THERE WILL BE ADDITIONAL RESEARCH THAT'S NEEDED BASED ON SOME OF THOSE PROPOSALS STARTING TO TAKE EFFECT. SO WITHIN THE UNITED STATES, IRBs REALLY START TO BECOME--ALTHOUGH THERE WERE CERTAIN KINDS OF RESEARCH STRUCTURES AND REVIEW, ETHICAL REVIEW STRUCTURES THAT EXISTED ALONGLET WAY, THEY BEGAN TO REALLY BECOME FORM ALIZED IN THE EARLY 1970S. A LOT OF THIS MOVEMENT WAS IN RESPONSE TO THE REVELATIONS ABOUT CONGRESSIONAL ACTIVITY AROUND THE SYPHILIS TRIAL, AND THAT LED TO THE CREATION OF THE--THE NATIONAL RESEARCH ACT AND CREATION OF THE NATIONAL COMMISSION FOR THE PROTECTION OF HUMAN SUBJECT AND BIOMEDICAL AND BEHAVIORIAL RESEARCH. IF YOU HAVEN'T ALREADY, YOU WILL BE A SESSION ON THE CYSTRY OF RESEARCH ETHICS THAT WE'LL TALK ABOUT THIS IN MORE DETAIL BUT THIS A PROLIFIC MISSION THAT PUBLISHED AMONG OTHER THINGS, THE BELMONT REPORT WHICH ARTICULATED A SET OF PRINCIPLES TO OVERSEE HUMAN SUBJECTS RESEARCH THOSE BECAME CODIFIED IN 1981 WHICH FORMALLY SPECIFIED REQUIREMENT AND FUNCTION OF IRBs AS WELL AS THE ELEMENTS OF INFORMED CONSENT THAT WERE RESPONSIBLE FOR REVIEWING AND INSURING WHAT WERE IN PLACE. A DECADE LATER THIS CELT OF REGULATIONS WAS ADOPTED BY ALL OF THE FEDERAL AGENCIES, 15 IN TOTAL. THAT WERE FUNDING RESPONSORRING FOR HUMAN SUBJECTS EVER, SUBPART A WERE ADOPTED IN WHAT WE REFER TO AS THE COMMON RULE. THE FDA HAS A LARGER SET THAT PERTAIN TO RESEARCH THAT WE'RE RESPONSIBLE FOR REGULATING. NOW MANY OF YOU MAY HAVE HEARD THERE'S BEEN SOME OTHERS IN PLAY FOR A NUMBER OF YEARS NOW TO TRY TO UPDATE AND REVISE THE COMMON RULE AS RECENTLY AS LAST YEAR. 2015 IS WHAT WE REFERRED TO AS THE NOTICE OF PROPOSED RULE MAKING OR NPRM. A PUBLISHED SET OF PROPOSED CHANGES FOR PUBLIC COMMENT THAT WENT OUT AND THE COMMENTS CAME IN AND WE'RE ALL WAITING TO SEE IF THE FINAL RULE IS GOING TO BE RELEASED WITHIN, DAYS, WEEKS, MONTHS. WE'RE NOT SURE WHEN IT'S GOING TO COME OUT BUT THERE MAY BE SOME CHANGES THAT WILL BE OF INTEREST THAT WILL EFFECT THE THINGS I WILL SHARE WITH YOU TODAY. BUT IN GENERAL THE IDEA OF INSTITUTIONAL REVIEW BOARDS, THAT'S A TERM WE USE WITHIN THE UNITED STATES BUT THERE ARE MANY OTHER TERMS THAT ARE USED, SOME ARE ADOPTED BY INDIVIDUAL INSTITUTIONS AND IN OTHER COUNTRIES, SO RESEARCH ETHICS, COMMITTEES, ETHICS REVIEW BOARDS, A NUMBER OF DIFFERENT TERMS BUT THE IDEA IS THAT THIS IS A GROUP THAT INDEPENDENT OF THE RESEARCH TEAM THAT'S CHARGED WITH WITH REVIEWING THE RESEARCH, IT'S THE ETHICAL REQUIREMENT FOR INDEPENDENT REVIEW LOOKS AT THE DESIGN OF THE STUDY, WHAT POPULATION IS PROPOSED TO THE STUDY, THE RISK BENEFIT, ASSOCIATED WITH THE CONDUCT OF THE RESEARCH AND THE GOAL AT A MINIMUM ARE BOTH TO MINIMIZE THE CONFLICTS OF INTEREST THAT RESEARCHERS WHO ARE DESIGNING AND ENTERING UP STUDIES BRING TO THE TABLE TO PROVIDE AN INDEPENDENT SOURCE OF OVERSIGHT TO INSURE THAT ALL OF THESE PRINCIPLES HAVE BEEN MET IN AN APPROPRIATE WAY. AND ALSO TO ASSURE THE PUBLIC THAT THERE IS THIS ACCOUNTABILITY THAT RESEARCHERS AND RESEARCH FUNDERS HAVE TO MAKE SURE THAT THIS BENEFITS THE PUBLIC IS BEING DONE IN A WAY THAT'S RESPONSIBLE AND ETHICALLY SOUND. SO IRBs AT A GLANCE. I HAVEN'T BEEN ABLE TO FIND A NUMBER UNLESS I WENT TO THE REGISTER AND FOUND IT, THERE ARE PROBABLY MORE THAN 4000. THIS IS A 2008 CALENDAR AND HUNDREDS OF ADDITIONAL TYPES OF MEMBERS IN OTHER COUNTRIES, THEY ARE ROUGHLY 14-40 MEMBERS, SOME OF THE LARGER MEMBER IRBs HAVE ALTERNATE PLAINTIFF'S EXHIBITS SO HAVE YOU A PARTICULAR ROLE AND YOU HAVE MORE THAN 1 PERSON AVAILABLE TO BE ABLE TO FULFILL THAT ROLE, SOME OF THE IRBs HERE UTILIZE THAT KIND OF A SYSTEM TO INSURE THAT YOU ALWAYS HAVE THE RIGHT KIND OF EXPERTISE AT THE TABLE. IRBs OFTEN HERE AT THE NIH TEND TO MEET 1-2 TIMES A MONTH DEPENDING ON THE VOLUME, AND NUMBER OF PROTOCOLS THAT THEY'RE RESPONSIBLE FOR VIEWING. ALTHOUGH I KNOW THERE ARE SOME COMMERCIAL IRBs FOR EXAMPLE THAT HAVE MEETINGS WEEKLY AND EVEN MULTIPLE TIMES A WEEK. SO THIS CAN VERY TREMENDOUSLY. INCREASINGLY, WE'RE SEEING IRBs, BEING STAFFED BY FULL-TIME ADMINISTRATORS AND IRBCOORDINATORS AND AT THE TIME I'VE BEEN AT THE NIH, I'VE SEEN A PROFESSIONALIDESSATION OF THIS ROLE WHERE THERE'S ACTUALLY CREDENTIALLY, A PRIMER, THE ORGANIZATION CALLED PRIMARY REVIEWERRER, PUBLIC RESPONSIBILITY IN MEDICINE AND RESEARCH, IT'S A CERTIFIED IRB PROFESSIONAL CREDENTIAL THAT MANY FOLKS HERE AT THE NIH FOR EXAMPLE WOULD HAVE, BUT A COMBINATION OF A TEST, CONTINUING EDUCATION REQUIREMENTS. THE CHAIR, IN EITHER A FULL-TIME OR PART-TIME CAPACITY DEPENDING ON HOW THE POSITION IS STRUCTURED, INFORMALLY WHEN I WAS DECIDING TO TAKE ON THE ROLE, OF THE CHAIR AS THE NHGRI, I SERVE THE OTHER IRB CHAIRS HERE AT THE NIH AND I DISCOVERED THAT THEY FACILITATE THAT ROLE AT 15 AND A HUNDRED% OF THEIR TIME, AGAIN, DEPENDING ON THE SIZE OF THEIR IRBs, THE WAY IT WAS STRUCTURED AND TOA WHAT EXTENT THEY HAVE A LARGE STAFF TO SUPPORT THEM. IRBMEMBERSHIP, THE REQUIREMENT FOR I RB MEMBERS, THEY HAVE TO HAVE AT LEAST 5 MEMBERS, AND THE GOAL IS TO HAVE QUALIFIED DIVERSE MEMBERS, NOT ALL MEN, OR WOMEN FROM THE SAME PROFESSION. THERE'S A REQUIREMENT TOW HAVE AT LEAST 1 SCIENTIST WITH EXPERTISE IN THE AREAS OF RESEARCH THAT ARE BEING REVIEWED, 1 NONSCIENTIST. THERE HAS TO BE SOMEBODY UNAFFILIATED WITH THE INSTUITION WHERE THE IRB IS LOCATED. THERE'S AN EFFORT TO REVIEW CONFLICTS OF INTEREST TO INSURE THAT THEY WILL NOT HAVE A CONFLICT WITH ANY OF THE PROTOCOLS THAT THEY WILL BE REVIEWING ON A REQUIREMENT THAT MEMBERS RECRUISE THEMSELVES IF A STUDY COMES UP THAT THEY'LL HAVE A CONFLICT WITH FOR SOME REASON AND THERE'S ATTENTION PAID TO INSURING THAT SPECIALIZED AREAS OF EXPERTISE ARE REPRESENT SAID FOR DIFFERENT KINDS OF STUDIES. THE NIH POLICIES AROUND IRB MEMBERSHIP GO INTO A LOT MORE DETAIL AND SPECIFICITY. THERE'S A REQUIREMENT THAT THE THAT THE NONAFFILIATED MEMBER OR MEMBERS AS WELL AS A MEMBER WHO REPRESENTS PARTICIPANT PERSPECTIVE. THAT MIGHT BE THAT SAME PERSON, THE NONAFFILIATED MEMBER, MIGHT BE SOMEBODY ELSE, THE GOAL IS TO HAVE THEM BE PRESENT OF THE MAJORITY OF THE IRB MEETINGS IT PRIORITIZED THAT INDEPENDENT AND THAT SPEER TECTIVE THAT'S PART OF THE DELIBERATION. THERE'S A REQUIREMENT TO HAVE A MEMBER WHO'S A BIOETHICIST AND THAT CAN ALSO BE FILLED BY INSURING THEY HAVE REGULAR ACCESS TO CONSULTATION THROUGH THE DEPARTMENT OF BIOETHICS. THERE'S A REQUIRED STATISTICIAN OR EPIDEMIOLOGIST, PHARMACIST OR PHARMACOLOGIST. A REQUIREMENT THAT IRB STAFF MEMBERS CANNOT SERVE AS IRB MEMBERS AND THEN DEPENDING ON THE TYPES OF STUDIES, THE IRB MIGHT BE EXPECTED TO HAVE PEDIATRIC EXPERTISE IF THEY'RE REVIEWING STUDIES THAT INVOLVE A PEDIATRIC POPULATION. THE REGULATIONS, REQUIREMENT FOR A PRISONER REPRESENTATIVE IF PRISONER SETTINGS WILL BE REVIEWED UNDER VERY SPECIFIC GUIDELINES. SO AN IRBs HAVE THE ABILITY TO BRING IN ADHOC EXPERTISE, ANYTIME THEY'RE REVIEWING A COMPLICATED STUDY WHEN WE HAVE REVIEWED GENE TRANSFER PROTOCOLS, WE BROUGHT IN ADHOC EXPERTS IN THE SPECIFIC SAFETY OR VECTOR THAT'S BEING USED. SOMEBODY WHO COULD SIT AT THE TABLE AND HELP US DELIBERATE DOESN'T COUNT TOWARDS THE VOTE OR THE DECISION THAT'S MADE BY THE IRB OR AUGMENT OUR ABILITY TO REALLY DELVE INTO THE SAFETY ISSUES FOR THAT KIND OF STUDY. I WANT TO FOCUS IN--1 OF MY PARTICULAR INTERESTS AS AN I RB CHAIR IS TO GIVE A VOICE TO THE NONSCIENTIST MEMBERS OF THE BOARD. I FEEL THIS IS VERY IMPORTANT AND OUR NIH POLICIES DEFINE THIS ROLE ANY BIOMEDICAL OR BEHAVIORIAL SCIENTIFIC DISCIPLINES. AND OTHERS HAVE ATTEMPTED TO DEFINE THIS ROLE IN SLIGHTLY DIFFERENT WAYS. SOMEBODY WHO CAN FULLY APPRECIATE THE RISK THAT'S ASSOCIATED WITH THE STUDY WITHOUT BEING BLINDED BY THE LURE OF SCIENTIFIC ADVANCEMENT. THAT'S A PARTICULARLY SHARPLY FOCUSED WAY OF PUTTING THE PERSPECTIVE OF A NONSCIENTIST. AND SOME OF OUR FORMER COLLEAGUES HERE AT THE NIH DID A SURVEY BACK IN 2008 OF THE NONSCIENTIST MEMBERS OF OUR INTRA MURAL IRBs AND THEY--THEY SURVEY 25 PEOPLE IN THAT ROLE. WHO ARE ASKED WHETHER THEY VIEWED THEIR OWN ROLE IN THE FOLLOWING POSSIBLE WAYS AND YOU COULD SEE A MAJORITY OF THEM, 68% USE THEIR ROLE AS THAT OF BEING A LAY PERSON. ONLY 28% VIEW THEMSELVES AS BEING A PUBLIC REPRESENTATIVE, FEWER, 16% SAW THEM AS A COMMUNITY, REPRESENTATIVE OF SOME PARTICULAR COMMUNITY AND ONLY 16% OF BEING A RESEARCH SUBJECT ADVOCATE. AND THAT LATTER FINDINGS IS INTERESTING WHEN COMPARED TO STUDIES THAT HAVE BEEN DONE OF THE NONSCIENTIST ROLE IN NONNIH SETTINGS. WHERE A MAJORITY OF THE NONSCIENTIST MEMBERS VIEWED THEMSELVES AS BEING THE VOICE OF HUMAN SUBJECTS OF BEING THAT RESEARCH SUBJECT ADVOCATE. THIS STUDY ALSO COMPARED WHAT THE NONSCIENTIST AND THE SCIENTIST MEMBERS OF THE IRB, HOW THEY VIEWED THIS ROLE AND DID COMPARISONS. SO THE NONSCIENTIST, 72% OF THEM VIEWED THEIR MAIN ROLE AS BEING TO REVIEW AND MAKE RECOMMENDATIONS ABOUT THE INFORMED CONSENT DOCUMENT BEING THE PERSON WHO CAN SIT THERE AND READ IT WITH SORT OF A NONSCIENTIFIC MIND AND MAKE SURE THAT IT'S CLEAR AND STRAIGHT FORWARD AND ONLY 47% OF THE SCIENTIST MEMBERS THOUGHT THAT THAT'S WHAT THE NONSCIENTIST SHOULD BE DOING. REPRESENTING COMMUNITY VALUES, VIEWS AND NORMS. 60%OT PART OF THE NONSCIENTIST AND A MUCH HIGHER PROPORTION THOUGHT THAT THAT'S WHAT THIS ROLE WAS ABOUT AND TO MAKE THE CONDUCT OF RESEARCH ACCOUNTABLE TO THE PUBLIC, 88% VERSUS 93%. SO IT'S INTERESTING AND I ALWAYS SHARE THIS PAPER WITH OUR NONSCIENTIST MEMBERS. WE HAVE, I THINK 3, RIGHT NOW ON OUR IRB, AND MY GOAL IS TO ENCOURAGE THEM TO BE THE ROLE AS SOMETHING THAT INCLUDES BUT IS NOT LIMITED TO THE REVIEW OF CONSENT FORMS BECAUSE I THINK THEY ARE A VERY IMPORTANT BALANCING, THEY FEEL INITIALLY INTIMIDATED SPEAKING UP AND VOICING THEIR PERSPECTIVE SIDE BY SIDE WITH A SCIENTIST AND EXPERTS SO THIS IS A BIT OF A CHALLENGE TO TRY TO JUGGLE AND THAT REQUIRES EXTRA TRAINING. VERY FORM AT ASPECTS OF THE IRB REVIEW PROCESS. IRBs ARE RESPONSIBLE FOR OVERSEEING THE STUDY FROM THE TIME IT'S PROPOSED TO THE TIME IT BEGAN AND THE TIME WHICH IT'S OVER AND CLOSE TED OUT. SO INITIALLY, WE DO INITIAL REVIEW OF THE PROTOCOL, WE'RE REQUIRED TO DO THE STUDY ON AN ANNUAL BASIS DURING THE CONTINUING REVIEW, ANY CHANGE VS TO BE SUBMITTED TO THE IRB FOR REVIEW AND APPROVAL IN THE FORM OF AMENDMENT AND WE TAKE A CLOSE LOOK AT AUDIENCE ANTICIPATED PROBLEMS THAT MIGHT COME UP ALONG THE WAY, THESE ARE THINGS THAT ARE UNEXPECTED, THAT ARE RELATED OR SEEM TO BE RELATED TO THE RESEARCH, AND THAT MAY SHIFT OUR UNDERSTANDING OF THE RISK OF THE RESEARCH TO PARTICIPANTS. AND SO MIGHT RESULT IN NEEDING TO ADAPT, SOMETHING ABOUT THE STUDY DESIGN OR SOMETHING ABOUT THE DISCLOSURE FOR EXAMPLE, THINGS WE HAVE TO TAKE SERIOUSLY, WE HAVE TO REVIEW ALLEGATIONS OF NONCOMPLIANCE AND INVESTIGATOR WHO'S NOT PERHAPS FOLLOWING THE POLICIES AND PROCEDURES OR IS DEVIATING FROM WHAT'S IN THE PROTOCOL AND LARGELY UNINTENTIONAL VARY OCCASIONALLY, IT'S MORE SERIOUS THAN AND THEN EVEN AT THE TIME THE STUDY IS COMPLETED, ALL THE DATA HAS BEEN COLLECTED AND ANALYZED AND THE RESEARCH KEQUESTIONS HAVE BEEN ADDRESSED WE LOOK AT HOW THE STUDY HAS BEEN CLOSED OUT. THE DATA DURING THE STUDY ARE GOING TO BE STORED, WHETHER ULTIMATELY OF THE PROMISES THAT WERE MADE TO SUBJECTS IN TERMS OF FOLLOW UP AND MANAGEMENT OF RESULTS, ALL THOSE EXPECTATIONS HAVE BEEN MET. SO, STUDIES DON'T JUST FIZZLE AWAY, THEY HAVE TO ACTIVELY BE CLOSED AND THAT HAS TO BE APPROVED BY THE IRBs TO INSURE THAT ALL OF THOSE DETAILS ARE ATTENDED TO. WE HAVE A SET OF REVIEW STANDARDS THAT HAVE BEEN DEVELOPED TO HELP GUIDE THE IRBs THROUGH THIS PROCESS, AND WE TEND TO MAKE THESE AVAILABLE TO THE INVESTIGATORS TO UNDERSTAND WHY IT IS WE'RE ASKING THEM FOR DETAILED INFORMATION IN A BROAD RANGE OF CATEGORIES. SO THE FIRST STANDARDS THAT HAS TO BE MET IS THAT THE PROPOSED RESEARCH DESIGN HAS TO BE FOUND AND CAN'T UNNECESSARILY EXPOSE SUBJECTS TO RISK AND THIS CORRESPONDS TO SOME OF THE BASIC PRINCIPLES THAT YOU'VE HEARD ABOUT ABOUT WHAT MAKES RESEARCH ETHICAL. YOU CAN'T--YOU CAN'T ASK THEM TO PARTICIPATE IN THE STUDY WHERE THE SCIENCE IS NO GOOD TO BEGIN WITH, THERE HAS TO BE A REASON TO EXPOSE THEM TO ANY LEVEL OF RISK. THE SECOND REVIEW STANDARD, THE RISKS HAVE TO BE REASONABLE IN RELATION TO THE ANTICIPATED BENEFITS OF THE STUDY AND THE SOCIETAL BEN FILTRATION RATES, THE KNOWLEDGE TO BE GAINED. THE RISKS THAT SUBJECTS WILL BE EXPOSED TO HAS TO BE MINIMIZED TO THE EXTENT POSSIBLE. SO WE LOOK CLOSELY AT HOW CONFIDENTIALITY WILL BE MANAGED AND HOW DIFFERENT PROCEDURES WILL BE CONDUCTED AND IF THERE'S A WAY TO MINIMIZE BUSHEDDEN AND POTENTIAL HARMS SOCIALITIED WITH THOSE PROCEDURES AND WE HAVE A DATA MONITORING PLAN AND STUDIES HAVE TO HAVE A DATA MONITORING PLAN IN PLACE THAT THE IRB APPROVED TO INSURE THAT PROBLEMS THAT COME UP ALONG THE WAI ARE IDENTIFY INDEED A TIMELY MANNER AND ADDRESSED. WE TAKE A LOOK AT THE SELECTION OF SUBJECTS AND WHETHER IT'S APPROPRIATE AND EQUITABLE. WE LOOK AT WHETHER THERE'S A NEED FOR ADDITIONAL SAFE GUARD FOR CATEGORIES OF VULNERABLE PARTICIPANTS SO ASCENT, FOR CHILDREN AND MONITORING AND ADULTS WHO MAY LACK THE CAPACITY TO CONSENT AS SOME EXAMPLES. THERE'S A FOCUS THEN ON THE INFORMED CONCERT PROCESS AND IN CASES WHEN CONSENT NEEDS TO BE OBTAINED WE LOOK CAREFULLY AT THE DOCUMENTATION AS WELL AS SETTING IN WHICH CONSENT WILL BE ADMIN I FELTERED. THERE ARE CONDITIONS UNDER WHICH THE IRB CAN APPROVE A WAIVER OR ELEMENTS OF INFORMED CONSENT OR REQUIREMENTS OF DOCUMENTATION OF INFORMED CONSPENT THOSE REQUIREMENTS ARE SPELLED OUT IN THE REGULATION. AND WE ALSO LOOK CAREFULLY AT THE LANGUAGE THAT WILL BE PRESENTED TO CHILDREN TO EXPLAIN RESEARCH TO THEM AND INSURE THAT IT'S UNDERSTANDABLE TO THEM AT THE READING LEVEL THAT WE EXPECT THAT THEY MIGHT BE AT, BASED ON THEIR AGE AND THEIR EXPERIENCE. WE ALSO REVIEW ASCENT FORMS FOR ADULT WHO IS MIGHT BE COGNITIVELY IMPAIRED BUT IN SOME WAYS IN IN PROCESS, SO I THINK I ALREADY MENTIONED THAT WE LOOK CLOSELY AT THE PRIVACY AND CONFIDENTIALITY PROTECTION TO INSURE THAT DATA WILL BE CODED AND ONLY SHARED WITH PEOPLE THAT ARE AUTHORIZED WHO HAD IT WHO HAD APPROPRIATE TRAINING AND KNOW HOW TO PROTECT THE CONFIDENTIALITY OF PARTICIPANTS. THERE ARE SOME ADDITIONAL CONSIDERATIONS THAT WE AS IRBs NEED TO PAY ATTENTION TO THAT ARE IN OUR POLICIES, WE WANT TO MAKE SURE THAT THE INVESTIGATORS AND RESEARCH STAFF ARE APPROPRIATLY TRAINED. THERE ARE DETAILED REQUIREMENTS AND ENTIRE SUBERATE S. O. P. IN FACT FOR THE TRAINING OF PIs AND PEOPLE ENGAGED IN DIFFERENT CATEGORIES OF RESEARCH, CURRENTLY REVIEWING WHAT'S GOING TO BE REQUIRED FOR REFRESHER COURSES, SOMETHING THAT NEEDS TO BE UPDATED EVERY 3 YEARS. IF IONIZING RADIATION WILL BE USED IN THE CONDUCT OF RESEARCH, THERE'S A REQUIREMENT FOR COMMITTEE REVIEW AND THE IRB NEEDS TO BE NOTIFIED ABOUT THAT BECAUSE IT RESULTS IN SPECIFIC LANGUAGE ABOUT THOSE RISKS INCLUDED IN RESEARCH. IN THE CASE OF COLLABORATIVE RESEARCH, INVOLVING OTHER SITES, OTHER SITES THAT ARE ENGAGED IN THE RESEARCH, THERE'S A LOT OF ATTENTION THAT MEDES TO BE PAID TO WHAT LOCAL REVIEWS ARE IN PLACE OR INCREASINGLY--AND I'LL SAY MORE ABOUT THIS IN A BIT--A RELIANCE ON THE INSTITUTIONS WE DO AND INSURING THAT THE DOCUMENTATION IS IN PLACE. FDA REGULATED RESEARCH ENTAILS A WHOLE ADDITIONAL LEVEL OF REVIEW AND DOCUMENTATION TO LOOK AT THE INVESTIGATOR BROCHURES, TO INSURE THERE'S IND IN PLACE OR IDE, THERE'S A WHOLE SEPARATE SET OF POLICIES AND PROCEDURES AROUND FDA REGULATED RESEARCH AND THE IRB HAS THE DISCRETION, I MENTIONED THAT WE NEED TO TAKE A LOOK AT RESEARCH, AT LEAST ANNUALLY FROM THE POINT IN TIME AT WHICH IT'S INITIALLY BEEN APPROVED BUT THERE ARE CASES IN WHICH THE IRB MAY CHOOSE TO ASK TO SEE A STUDY AGAIN BEFORE THAT YEAR IS UP. SO SOMETIMES AFTER THE FIRST PARTICIPANT IS ENROLLED OR AFTER 6 MONTHS BECAUSE WE WANT TO SEE IF THE SAFETY MEASURES THAT WERE PUT INTO PLAY ARE ADEQUATE AND TO SEE IF THE ADVERSE EVENT RATE IS AS LOW AS WE HOPED. SO SOMETIMES FOR THE COMPLICATED STUDIES WE MIGHT ASK TO SEE A STUDY MORE OFTEN THAN ANNUALLY. SO, THE IRB FUNCTIONS LARGELY LIKE OTHER COMMITTEES THAT YOU MIGHT BE FAMILIAR WITH, YOU FOLLOW THROUGHOUT THE BORDER AND WE MIGHT SAY, THAT A STUDY IS UNCONDITIONALLY APPROVED. YOU MIGHT STIPULATION DEFERRED WHICH MEANS YOU HAVE TO COME BACK TO THE IRB WITH CHANGES BEING MADE AND MIGHT BE TABLED BECAUSE WE DON'T HAVE QUITE ENOUGH INFORMATION TO ADDRESS ALL OF THE REVIEW CRITERIA AND IT MIGHT EVEN BE DISAPPROVED BUT THOSE DETAILED MINUTES THAT ARE WRITTEN UP TO DOCUMENT ALL OF THE IRBs DETERMINE NATION AT GREAT LENGTH ARE--THEY TEND TO BE IN THE 20 OR 30 PAGES, WE HIRE A PROFESSIONAL CONTRACTOR TO WRITE UP THE MINUTES AND THEY'RE FAMILIAR WITH THE REGULATION AND KNOWS HOW TO MAKE SURE AND HELPS THE IRB KEEP TRACK OF EVERYTHING IT'S REQUIRED TO DOCUMENT UNDER THIS INCREASINGLY ELABORATE SET OF POLICIES AND PROCEDURES. FOR CERTAIN KINDS OF RESEARCH WE'RE PERMITTED TO DO A CERTAIN KIND OF REVIEW, MEANING IT DOESN'T HAVE TO HAVE A FULL MEETING, AND A QUORUM PRESENT, AND A VOTE, IT MEANS WE CAN USE JUST THE COMMITTEE CHAIR AND DO GUIDANCE RESURE, AND WE CAN SOMETIMES DO REVIEWS FOR AN EXPEDITED PROCEDURE, AT TIMES I PROPOSE CHANGES TO THE COMMON RULE, 1 OF THE PROPOSALS WAS MADE TO ELIMINATE THE REQUIREMENT FOR CONTINUING REVIEW FOR CERTAIN CATEGORIES OF RESEARCH THAT ARE CONSIDERED TO BE EXPEDITABLE FOR A MINIMAL RISK SO THAT WILL BE AN INTERESTING CHANGE TO KEEP AN EYE ON IF THAT ULTIMATELY GOES THROUGH. SO NOW TURNING TO THE PROPOSAL 6 IRBs, I WILL MENTION, I WILL TALK ABOUT ACCREDITATION AND THEN THE 2 IN THE MIDDLE TOGETHER. SO AAAHRPP, I THINK IT'S ACCREDITABLE ASSOCIATION FOR HUMAN RIGHTS PROTECTION PROGRAM, IT'S THE ACCREDITATION THAT ACCREDITED THE NIH PROGRAM, I LOOKED AT THE WEB SITE AND THEY ACCREDITED 227 RESEARCH ORGANIZEERATIONS, THEY SAY THEIR GOALS ARE AS FOLLOWS TO IMPROVE THE SYSTEMS THAT PROTECT THE RIGHTS AND WELFARE OF RESEARCH PARTICIPANTS AND TO ENHANCE PUBLIC COMMUNICATIONS OR PUBLIC ACCOUNTABILITY, PIECE ABOUT HOW THOSE INSTITUTIONS ARE DOING SO THE RIVIEW PROCESS IS VERY--I MEAN THE ACCREDITATION PROCESS IS VERY DOCUMENTATION AND IRB PROCESS FOCUSED SO THEY'RE VERY INTERESTED IN LOOKING AT S. O. P.s, MINUTES PROTOCOLS AND MAKING SURE THAT IN WRITING WE ARE DOING EVERYTHING BY A VERY ELABORATE AND WELL DOCUMENTED SET OF STANDARDS AND SO THIS HAS LED FOR EXAMPLE AT THE NIH TO THE ESTABLISHMENT OF I THINK 42 DIFFERENT S. O. P.s THAT ALL OF THE DIFFERENT--DEZEN DIFFERENT IRBs HERE IN THE INTRA MURAL RESEARCH PROGRAM AND WE ALL FOLLOWED THESE S. O. P.s AND ALTHOUGH IT WAS A PRETTY ELABORATE PROCESS TO GET ALL OF THAT INTO PLACE, I HAVE TO SAY AS A RELATIVELY NEW IRB CHAIR, 2014, IT'S VERY HELPFUL TO HAVE THIS STANDARD SET OF DOCUMENTS TO REFER TO THIS AS A STARTING POINT FOR IN SHOULD OF THE NEW THINGS COMING UP, THERE'S SO MANY DETAILS TO KEEP TRACK OF AND THEY'RE AVAILABLE ON THIS PUBLIC--PUBLICLY ACCEPTABLE, PUBLIC WEB SITE IF YOU'RE INTERESTED AND WANT TO TAKE A LOOK. SO THAT ADDRESSES AT LEAST THE DOCUMENTATION PIECE, IT DOESN'T SPEAK TO HOW IRBs ARE ACTUALLY PROTECTING HUMAN SUBJECTS IN PRACTICE. BUT IT HELPS TO INSURE THAT AT LEAST IRBs ARE FOLLOWING A FAIRLY CONSISTENT SET OF STANDARDS WHICH MIGHT HELP TO MINIMIZE SOME OF THE VARIABILITY AND PARTICULARLY PROBLEMATIC VARIABILITY WHERE IRBS MIGHT BE MISSING THINGS, ROOTS NOW PERHAPS SPELLED OUT IN GREATER DETAIL AND HAS THE ABILITY TO IMPROVE OUR ABILITY TO CARRY OUT OUR WORK. IT DOESN'T--THIS DOESN'T ADDRESS THE OTHER PROBLEM THAT'S BEEN MENTIONED, THE IDEA OF REPETITIVE IRB REVIEW. THE MULTISITE RESEARCH IS BEING CONDUCTED AND EACH SITE'S IRB HAS TO REVIEW THE PROTOCOL, THERE'S QUESTIONS ABOUT WHETHER THE VALUE TO HAVING THE LOCAL REVIEW, DOES IT UPHOLD EFFORTS TO PROMOTE LOCAL STANDARDS OF ETHICAL STANDARDS FOR RESEARCH, CAPITALIZED ON AN IRBs KNOWLEDGE OF LOCAL COMMUNITIES AND STANDARDS IN WAYS THAT ARE ENCOURAGED OR IS IT REDUNDANT AND INEFFICIENT, THOSE ARE THE QUESTIONS THAT HAVE BEEN ASKED. SO THE PROPOSED SOLUTION IS TO ENCOURAGE CENTRALIZATION OF IRB REVIEW, SO HAVING A SINGLE IRB OF RECORD FOR A MULTICENTER CLINICAL CENTER, FOR EXAMPLE. MORE DETAILED DEVELOPMENTAL ENDOCRINOLOGY NITION OF CENTRALIZED IRB HAS BEEN OFFERED A PROPERLY CONSITUTED IRB TO WHICH ALL SITES SEIZE ALL REGULATORY RESPONSIBILITY. IF I WERE WRITING THIS DEFINITION, I WOULD TAKE OUT THE WORD ALL BECAUSE THERE'S STILL SOME RESPONSIBILITIES THAT REMAIN AT THE PERFORMANCE SITE. SO THE RESPONSIBILITY FOR SCIENTIFIC OVERSITE AND INTEGRITY OF THE PROTOCOL FROM INI SHALL REVIEW TO DETERMINE NATION OF REVIEW, INCLUDING INFORMED CONSENT. SO THESE ARE DEFINITIONS THAT HAVE BEEN AUTHORED. THERE ARE A NUMBER OF EXAMPLES OF CENTRALIZED IRBs THAT EXISTED EVEN FOR A WHILE. THE NCI CENTRAL IRB IS A GOOD EXAMPLE, THE DEPARTMENT OF VETERAN AFFAIRS HAS CENTRALIZED IRB REVIEW SYSTEM THAT TAKES PLACE AS WELL AS MANY HOSPITAL SYSTEMS. NEURONEXT IS AN NINDS SPECIFIC NET WORK THAT UTILIZES CENTRALIZED IRB REVIEW PROCESS, THE NHGRI, UNDIAGNOSED DISEASES NETWORK IS AN EXAMPLE OF A SINGLE IRB, MY OWN IRB, ADAPTED TO BECOME THE SINGLE IRB TO THIS 1 STUDY, WHILE WE'RE STILL FUNCTIONING AS A QUOTE-UNQUOTE REGULAR IRB FOR A NUMBER OF REGULAR STUDIES THERE'S A HEALTH EMERGENCY REVIEW BOARD THAT'S BEING ESTABLISH INDEED OUR INTRA MURAL RESEARCH PROGRAM HERE AS WELL. THAT YOU CAN LOOK AT IF YOU'RE INTERESTED IN MORE DETAILS ABOUT THAT. SO THE ABILITY TO USE A MORE CENTRALIZED IRB MECHANISM HAS EXISTED FOR THIS MECHANISM TO DO RELIANCE AGREEMENT ON A VULUNSUPPORTED TARY BASES FOR SOMETIME, IT'S AN AGREEMENT BETWEEN THE NIH AND ASSIGNED RESPONSIBILITIES OF OVERSIGHT TO 1 OR THE OTHER INSTITUTIONS AND EITHER DIRECTION, THESE ARE OBSERVED BY AN OFFICE CALLED OHRB, THE OFFICE OF HUMAN AND AND THE MOMENTUM TOWARDS MAKING THIS WITH THE STUDIES, THE DEFAULT SHOULD BE TO TRY TO USING A SINGLE IRB, AND THIS IS EVIDENCE FOR THIS IN THE REALLY SINGLE USE OF THE IRB WHICH ESTABLISHES THIS EXPECTATION TO USE A SINGLE IRB OF RECORD WITH THE ETHICAL REVIEW OF NONEXEMPT HUMAN SUBJECTS RESEARCH BEING FUNDED BY THE NIH IN A MULTISITE MANNER IN THE UNITED STATES SO MORE THAN 1 SITE IN THE UNITED STATES. SO THIS DOESN'T NECESSARILY APPLY TO INTERNATIONAL RESEARCH, SO ALTHOUGH EVEN IN THAT SETTING, THERE'S STILL TED OPTION OF USING THE RELIANCE AGREEMENT IF ALL PARTIES ARE INTERESTED IN DOING THAT. SO THIS IS A NEW POLICY THAT EXISTS AND IS IN THE PROCESS OF BEING IMPLEMENTED THAT WILL BE HEARING ABOUT OVER THE NEXT FEW MONTHS TO SEE HOW IT'S ACTUALLY GOING TO PLAY OUT: THE RATIONAL FOR THE POLICY IS, PUT FORTH AS FOLLOWS THAT THERE'S LITTLE TO NO EVIDENCE THAT MULTIPLE IRB REVIEW ACTUALLY ENHANCES THE PROTECTIONS FOR HUMAN SUBJECTS IN MOST KINDS OF MULTISITE RESEARCH AND THERE'S AN ARGUMENT THAT THE USE OF SINGLE IRBs MAY LEAD TO ENHANCED BY RESEARCH PARTICIPANT BY ELIMINATING THE PROBLEMS ACROSS MULTIPLE EN--STRATEGIES TUITIONS, INMYSELFING CONFLICTS OF INTEREST, SO - I'M OVER HERE, THE CENTRALIZED IRB HAPPENS AT MULTIPLE SITES, I'M LESS LIKELY TO HAVE A CONFLICT OF INTEREST WITH THE RESEARCH TAKING PLACE AT ALL OF THOSE OTHER SITES. AND IT CAN HELP REFOCUS IRB FOR LOOKING AT THE MOST COMPLICATED AND ETHICALLY CHALLENGING KINDS OF STUDIES BY ELIMINATING THIS REDUNDANT REVIEW, SO THOSE WERE ARGUMENTS THAT WERE PUT FORWARD. WE WILL SKIP AHEAD A BIT AND TALK ABOUT WHAT SOME PEOPLE HAVE ARGUED AS COUNTERARGUMENTS FOR THE USE OF CENTRALIZATION OF IRBs. THERE'S A CONCERN ABOUT INSTITUTIONAL LIABILITY THAT THAT 1I RB IS GOING TO BE ASSUMING TOO MUCH LIABILITY FOR THE RESEARCH THAT'S HAPPENING AT ALL OF THESE OTHER SITES AND THERE'S BEEN A LOT OF LEGAL REVIEW OF THESE QUESTIONS. REAL CONCERN ABOUT THE LOSS OF COMMUNITY REPRESENTATION AND THE KNOWLEDGE THAT AN IRB HAS OF THE LOCAL SUBJECTS AS WELL AS INVESTIGATORS. THE QUALITY OF REVIEW, AND JUST THE CHALLENGES OF COORDINATING AND HAVING TO LEARN TO WORK IN THE NEW IRB, EACH TIME YOU INITIATE A NEW STUDY, MY PROCESSES HERE ARE GOING TO BE DIFFERENT THAN THE SUBMISSION PROCESSES AT ANOTHER INSTITUTION AND SO, IF INVESTIGATORS ARE NOT WORKING WITH THE LOCAL IRB BUT WHICHEVER IRB HAS BEEN DESIGNATED FOR A STUDY, THERE'S CONCERN ABOUT THAT COMPLEXITY THAT THAT'S MENTIONED AS WELL. BUT THIS IS SOMETHING THAT'S MOVING FORWARD AND THERE'S A SUBCOMMITTEE THAT'S LOOKS AT METRICS OF SUCCESS. LOOKING AT WHETHER IT IS IN FACT MORE EFFICIENT TO GO THIS WAY, TO LOOK AT HOW THE PROCESS IS IMPLEMENTED AND TO DEVELOP METRICS FOR MEASURING SUCCESS. I DO WANT TO MENTION THAT THE POLICY BUILDS IN CERTAIN TYPES OF EXEMPTIONS FOR RESEARCH. I MENTIONED, THE POLICY, I FORGOT TO MENTION THAT THE NPRM INCLUDES A SIMILAR PROPOSAL FOR THE CENTRALIZATION OF IRB REVIEW FOR COOPERATIVE RESEARCH PROTOCOL, THAT I THINK WILL PARALLEL AT LEAST TO SOME EXTENT TO ASSOCIATE THE NIH POLICY AS TAKEN. SO HERE THE NIH POLICY EXCEPTIONS ARE PERMITTED WHERE REVIEW BY A PROPOSED SINGLE IRB WILL BE PROHIBITED BY A FEDERAL TRIBAL OR STATE REGULATION OR POLICY AND FOR THOSE ARE SORT OF AUTOMATIC CATEGORICAL EXEMPTIONS THAT XYST AND THERE WILL BE A COMMITTEE THAT WILL EXPLAIN COMPELLING JUSTIFICATIONS THAT A INVESTIGATOR PRESENTS THAT NOT ONLY A SINGLE IRB BUT THE LOCAL IRB REVIEW FOR A GIVEN STUDY OUGHT TO BE REVIEWING THIS RESEARCH FOR SOME SPECIFICATION AND THERE'S ANOTHER SUBCOMMITTEE LOOKING AT WHAT SHAPE THOSE EXCEPTIONS OF WHAT THAT WILL LOOK LIKE THAT WE WILL HEAR MORE ABOUT OVER THE NEXT WEEKS AND MONTHS. THE TRIBAL POLICIES EXCEPTION IS 1 THAT'S VERY IMPORTANT. THERE'S A NUMBER OF COMMENTS THAT WERE SUBMITTED WHEN THE NIH POLICY WAS RELEASED AND THE ARGUMENT RANGE FROM WANTING TO MAKE SURE THAT TRIBAL RESEARCH WITH INDIGENOUS COMMUNITIES WITHIN THE UNITED STATES IS CONDUCTED IN A COMMUNITY ENGAGED MANNER. THE ARGUMENT THAT LOCAL IRBs OR TRIBAL IRBs ARE BEST SITUATED TO BE ABLE TO INSURE THAT THAT TAKES PLACE, AND MANY TRIPES HAVE AS A MATTER OF POLICY THAT THEIR OWN IRBs AND PROCESSES HAVE TO BE USED. IN ADDITION TO WHATEVER PROCESSES WILL EXIST. THERE'S AN INTEREST IN THIS MAKING SURE THAT RESEARCH IS APPROPRIATELY BALANCED WITH OTHER COMPETING NEEDS WITHIN THE COMMUNITY FOR EXAMPLE FOR DIRECT PATIENT CARE AND THAT FINDINGS, THOSE PROVISIONS IN PLACE THAT THEY WILL MAKE THEIR WAY BACK TO THE TRIBE THAT WILL HELP TO BENEFIT THEIR COMMUNITIES AND THERE ARE SPECIFIC REQUIREMENTS FOR EXAMPLE, FOR INDIAN HEALTH SERVICE IRBs TO BE CALLED UPON TO REVIEW RESEARCH THAT'S TAKING PLACE WITHIN IHS FUNDED FACILITIES OR TRIBAL IRBs IN OTHER KINDS OF CIRCUMSTANCES AND I JUST WANT TO END BY LETTING PEOPLE KNOW THERE WAS A PRIMR WEBBENER A FEW WEEKS AGO AND THE TRANSCRIPT IS PUBLICLY AVAILABLE. THEY MADE THIS FREELILY AVAILABLE TO THE PUBLIC THAT TALKS THROUGH TRIBAL OVERSIGHT AND GOVERNMENT RESEARCH AND HOW IT RELATES TO THE SINGLE IRB POLICIES, I WILL END ON THAT NOTE AND I LOOK FORWARD TO TAKING YOUR QUESTIONS. THANK YOU. [APPLAUSE ] [INAUDIBLE QUESTION FROM AUDIENCE ] >> WHERE SPECIFIC DETAILS ON YOU GET THE COMMUNITY RESEARCH OR THE IRB PARTICIPANTS FROM THE BROADER COMMUNITY, THE NONSCIENTISTS? >> GREAT QUESTION. THROUGH WORD OF MOUTH. OCCASIONALLY A VERY MOTE VOTED COMMUNITY REPRESENTATIVE AND OFFERS THEIR TIME TO OHRP WHO WILL GET THE WORD OUT. SOMETIMES WE TALK TO INVESTIGATORS WHO MIGHT HAVE A PARTICULARLY ENGAGED RESEARCH PARTICIPANT WHO MIGHT BE INTERESTED IN SURVEYING RESEARCH BEYOND THEIR PARTICIPATION AND WE GOT MEMBERS THAT WAY AND ALSO THROUGH THE ADVOCACY COMMUNITY AND IN MY CASE, A LOT OF RARE DISEASE PROTOCOLS AND A LOT OF ADVOCACY GROUPS THAT WE'VE ENGAGED WITH TO TRY TO IDENTIFY PEOPLE BUT YOU'RE ALWAYS LOOKING FOR MOTIVATED VOLUNTEERS SO WE'LL TAKE ALL COMERS IF YOU'RE AWARE OF ANY RESOURCES PLEASE SEND THEM. >> I WAS WONDERING IF YOU COULD SAY SOMETHING ABOUT THE SORT OF PROCESS OF DELIBERATION AT THE IRB? IN OTHER WORDS THERE ARE LOTS OF RULES AND ROBERTS RULES AND THINGS PEOPLE FOLLOW, REGULATIONS, ET CETERA, HOW MANY OF YOU HAVE BEEN TO AN IRB MEETING? MOST, WELL, MAYBE HALF. THERE'S A SORT OF LIVE PROCESS THAT GOES ON, SOMETIMES WHICH IS VERY SORT OF DEEP AND THOUGHTFUL ABOUT THE VERY DIFFICULT ISSUES THAT IRBs NEED TO MAKE DECISIONAND I WAS WONDERING IF YOU COULD SAY ANYTHING ABOUT THE PROCESS OR AN EXAMPLE OF SOMETHING THAT WAS YOU KNOW SORT OF TOOK A LONG TIME OR GAVE THE IRB LOTS OF THINGS TO CHEW ON OR SOMETHING LIKE THAT. >> GREAT, GREAT QUESTION. SO I'LL PHRASE ME ANSWER IN HOW WE TACKLE INITIAL REVIEWS OF STUDIES, SO IF THIS IS THE FIRST TIME THE IRB GRAPPLED WITH THE STUDY AS A BOARD. WE MAKE A POINT OF INVITING THE INVESTIGATOR TO COME TO THAT INITIAL MEETING AND TO SIT WITH US AND PROVIDE US WITH A DESCRIPTION OF THEIR PROTOCOL--THE IRB TO ASK THAT INVESTIGATOR A QUESTION AND TO GET CLARIFICATION ABOUT ABOUT THE STUDY WITH HIM OR HER MEMBERS OF THE PRESENCE IN THE ROOM. AND THAT I FIND IS A VERY USEFUL WAY TO GAIN A BETTER UNDERSTANDING OF WHAT WAS INTENDED BY WHAT'S WRITTEN, GOING FROM THE 2 DIMENSIONAL PAPER TO THE ACTUAL STUDY, IS SOMETIMES ENHANCED BY JUST SITTING AND HAVING A CONVERSATION. WE BUILD IN A LOT OF TIME FOR OUR INITIAL REVIEWS BECAUSE THE PROCESS CAN TAKE A WHILE AND THEN WE EXCUSE THE INVESTIGATOR AND THE TEAM AND WE DO DELIBERATE FOR QUITE A WHILE AND 1 OF MY GOALS AS A CHAIR, I THINK DIFFERENT IRBs HAVE DIFFERENT SORT OF TENDENCIES WHEN IT COMES TO VOTING ON PROTOCOLS, CHAIRS WILL STRIVE FOR CONSENSUS AND EVEN UAN IMPEDIMENTSITY, AND GET A POINT WHERE THEY'RE COMFORT, AND HAVING SAT IN ON IRBs FOR THE MEETING, MY OWN IRB, MY GOAL IS TO DRAW OUT THE DISSENTING VIEWS AND SEE IF WE COULD GET LESS AGREEMENT IN A WAY INITIALLY TO REALLY HEAR WHAT SOME OF THE MINORITY PERSPECTIVES AT THE TABLE MIGHT BE AND USE THAT AS A WAY TO WORK BACK TOWARD THINKING ABOUT, IF NOT CONSENSUS THAT LEAVES SOMETHING THAT MOST PEOPLE COULD AGREE ON AND THAT'S BEEN A CONSTRUCTIVE AND REALLY FUN AND ENGAGED PROCESS. MY MEMBERS ENJOY COMING TO THE MEETINGS. WE HAVE LIMITED TURNOVER THE MEMBERS BUT IT TAKES A LONG TIME AND SO WE HAVE MUCH LENGTHIER IRB MEETINGS, WE TEND TO HAVE 1 OF THOSE LOWER VOLUMES AMONG THE DIFFERENT IRBs SO WE JUST SORT OF MAKE UP FOR IT. IT'S THE TIME THAT WE HAVE AND HAVE LENGTHY INTERESTING DELIBERATIONS. AND THEN SO WE COME TO A VOTE. IT'S A SIMPLE MAJORITY VOTE. WE NOW OCCASIONALLY HAVE DISSENTING VIEWS THAT GET DOCUMENTED IN THE MINUTES AND THEN WE REPORT THIS BACK IDENTITY IN THE FORM OF MINUTES WHICH I THINK DON'T QUITE CONVEY THE NATURE OF THE FULL ENGAGEMENT THAT WE HAVE IN THESE DELIBERATIONS. BUT AT LEAST TALK ABOUT THE ISSUES THAT THE WORD IS KONT ROUGH ATOM VERTED THAT WERE ISSUES THAT WERE HARD ORDER TO GRAPPLE WITH FOR WHICH THE AGREEMENTS AND WE DOCUMENT CAREFULLY THE RATIONAL FOR THE DISSENTING VOTES AS WELL AND GET THAT INTO THE MINUTES. AND WE DO IT ALL AGAIN THE FOLLOWING YEAR, BUT IT'S USUALLY A LOT LESS TO DO THE SECOND TIME AROUND BECAUSE AT THAT POINT WE HAVE SOMETHING IN PLACE, TO WORK WITH AND WE'RE LOOKING TO SEE IF EVERYTHING STILL HOLDS TRUE WITH CHANGES TO THE PROTOCOL ALTER ANYTHING ABOUT OUR ORIGINAL ASSUMPTIONS WHEN WE PROPOSE THIS. THE INITIAL PROPOSAL IS THE 1 WE SPEND THE MOST TIME ON. >> GREAT. ANYBODY ELSE? QUESTIONS? [INDISCERNIBLE] AHHHH! [LAUGHTER] OKAY, THANK YOU SARAH. >> THANK YOU. [APPLAUSE ] ALL RIGHT FOR THOSE OF YOU LISTENING OR IN THE AUDIENCE WHO HAVEN'T BEEN TO AN IRB MEETING, I WOULD RECOMMEND IT BECAUSE IT'S A VERY INTERESTING INSIGHT INTO HOW DIFFICULT SOME OF THE JUDGMENTS ACTUALLY ARE. AND YOU KNOW PEOPLE WHO SIT ON IRBs TAKE IT VERY SERIOUSLY. SOMETIMES I THINK IT IS THE SORT OF VIEW OF SOME INVESTIGATORS, THE IRB IS GIVING ME A HARD TIME OR DOESN'T WHAT I'M REALLY TRYING TO DO BUT I THINK THE INTRA MURAL IRBs IN PARTICULAR MAKE A POINT OF TRYING TO BE VERY ENGAGED WITH THE INVESTIGATORS TO TRY TO MAKE SURE THE RESEARCH IS AS GOOD AS IT CAN BE. SO HOW NEXT SESSION IS ON FAIR SUBJECT SELECTION AND YOU MAY REMEMBER FROM THE FRAMEWORK WE TALKED ABOUT LAST WEEK, THIS IS 1 OF THE ELEMENTS, UNFORTUNATELY THE LECTURES THROUGHOUT THE COURSE ARE NOT IN THE ORDER OF FRAMEWORK MOSTLY BECAUSE OF SPEAKER'S SCHEDULES, SO WE ARE LUCKY TO HAVE DAVE WENDLER, WHO IS A SENIOR INVESTIGATOR IN THE DEPARTMENT OF BIOETHICS AND THE HEAD OF THE SECTION ON HUMAN SUBJECTS RESEARCH IN OUR DEPARTMENT WHO HAVE THOUGHT ABOUT THIS TOPIC AND WRITTEN ABOUT THIS TOPIC AS MUCH AS JUST ABOUT ANYBODY. DAVE? >> GOOD MORNING. CHRISTINE MENTIONED THIS BUT MY COMPENSATION FOR AGREEING TO GIVE THIS TALK IS ADVERTISING, SO I'M GOING TO ADVERTSIZE THAT THERE'S ETHICS GRAND ROUNDS IN THIS ROOM AT NOON SO ANYBODY WHO DOESN'T GET ENOUGH RESEARCH ETHICS, THIS MORNING, WE WILL WELCOME YOU BACK AND IT'S ACTUALLY APROPOE SUBJECT FAIR SELECTION. IT'S AN INTERESTING CASE ABOUT WHO SHOULD BE ABLE TO PARTICIPATE IN PHASE 1 TRIALS AND IT'S A CASE FOR US, A RARE CASE THAT WAS BROUGHT TO US BY A PATIENT WHO HAD SOME CONCERNS ABOUT THE ELIGIBILITY CRITERIA FOR 1 OF THE STUDIES THAT WE WANTED TO ENROLL IN BUT WASN'T ELIGIBLE FOR. IT SHOULD BE A GREAT DISCUSSION FOR ANYBODY AROUND. SO TAKE A BREAK AND COME BACK. OKAY, SO FAIR SUBJECT SELECTION, YOU PROBABLY HEARD THAT FROM A BUNCH OF US NOW, WE MAKE THIS UP OURSELVES AND NOBODY APPROVES IT AND SOME PEOPLE DISAPPROVE OF IT. SO, I THINK ABOUT FAIR--AS CHRISTINE MENTIONED FAIR SUBJECT SELECTION IS 1 OF THE STANDARDS IN THE 7 OR 8 PRINCIPLES, DEPENDING UPON HOW YOU COUNT THEM FOR ETHICAL RESEARCH AND I TEND TO THINK ABOUT THEM IN THIS WAY, SO THIS IS NOT NECESSARILY A STANDARD WAY OF DOING IT, BUT I THINK IT'S HELPFUL FOR THINKING ABOUT THE DIFFERENT ASPECTS OF CONDUCTING TRIALS THAT ARE RELEVANT TO SUBJECT SELECTION. SO FIRST IT'S JUST OBVIOUSLY SUBJECT SELECTION WHICH IS DETERMINING WHO'S ELIGIBLE AND WHO'S NOT ELIGIBLE TO BE IN A CLINICAL TRIAL AND AS I MENTION, THAT WILL BE THE DISCUSSION POINT FOR GRAND ROUNDS AT NOON. SO THAT'S THE FIRST PART AND THAT'S PROBABLY THE ASPECT OF THIS THAT GETS THE MOST ATTENTION AND YOU WILL SEE THAT MIRRORED IN MY TALK WHERE MOST OF WHAT I'LL TALK ABOUT IS THE FIRST 1. IN PART, I THINK BECAUSE OF IMPORTANCE BUT ALSO BECAUSE OF HOW MUCH HAS BEEN DONE ON IT AND I THINK THE SECOND AND THIRD 1S STILL NEED A LOT MORE WORK. SO RECRUITMENT IS BASICALLY YOU'VE DECIDED WHO IS ELIGIBLE FOR THE STUDY AND YOU HAVE TO DECIDE HOW TO TRY TO GET THEM TO ENROLL IN YOUR TRIAL AND THEN REATTENTION IS, THEY'VE ENROLLED ON YOUR TRIAL AND HOW DO YOU KEEP THEM ON THE TRIAL TILL YOU GET THE END POINTS THAT ARE SPECIALSIFIED FOR YOUR PROTOCOL FOR GETTING THE DATA YOU WANT SO YOU WILL GO THROUGH THESE 3 ASPECTS AND HOPEFUL THIS IS FAMILIAR, THIS IS BASED ON THE FRAMEWORK AND THE THOUGHT HERE IS THAT IN GOING THROUGH THESE ASPECTS OF FAIR SUBJECT SELECTION, THESE GOALS PROVIDE A FRAMEWORK FOR THINKING ABOUT HOW TO DO IT, AS WE GO ALONG WE WILL SEE MANY OF THESE HERE THAT REMAIN TO BE ADDRESSED AND HOPEFULLY THIS FRAMEWORK IS NOT PROVIDING A WAY TO ANSWER THOSE CHALLENGES, AT LEAST PROVIDE A WAY FOR INVESTIGATORS AND I RBs TO THINK ABOUT THEM AND TRY TO ADDRESS THEM. AS YOU GO THROUGH THE 3 ASPECTS. OKAY SO OBVIOUSLY WHEN YOU HAVE A BUNCH OF GOALS THEY MIGHT CONFLICT AND THIS FRAMEWORK ISN'T GOING TO PROVIDE YOU A CLEAR SPECIFICATION ABOUT HOW YOU SHOULD PROCEED IN CASES OF CONFLICT, AND THAT'S BECAUSE I DON'T KNOW HOW TO FIGURE OUT EXACTLY HOW TO DO THAT IN A GENERAL WAY. I THINK WHAT YOU JUST NEED IS YOU NEED SMART PEOPLE WHO UNDERSTAND A SPECIFIC CASE AND USE THE JUDGMENT TO FIGURE OUT WHICH OF THE CONSIDERATIONS ARE MORE IMPORTANT ON THAT CASE SO WHO OF THE ELEMENTS I SAID WE SHOULD MIN MIDS RISK AND THE OTHER WE SHOULD INCREASE THE VALUE OF SOCIAL SCIENCE AND THOSE 2 CONNECTICUT FLICK ALL THE TIME, SO YOU MIGHT WANT TO EXCLUDE PEOPLE THAT ARE VERY SICK, THAT COULD BE WAYS TO MINIMIZE THE RISK OF STUDY BUT THEN YOU MIGHT LEARN ABOUT HOW YOU WORK ON DRUGS THAT ARE VERY SICK. AS A RESUMMIT, THE STUDY MIGHT NOT BE AS VALUABLE AS THEY WOULD OTHERWISE AND WHAT IRBs DO ALL THE TIME AND HOW DO BALANCE THOSE 2 CONSIDERATIONS AND PEOPLE NEED TO FIGURE THIS OUT. BALANCE THEM, USING THEIR JUDGMENT, IN THE SPECIFIC CASES, OKAY. SO SPARE SUBJECT SELECTION, STARTING WITH SUBJECT SELECTION, AS A MENTIONED THIS IS ABOUT WHO CAN GET INTO THE TRIAL, IRBs DO THAT BASED ON INCLUSION AND EXCLUSION CRITERIA, YOU HAVE TO BE AT LEAST 18 YEARS OLD, YOU HAVE TO HAVE A CERTAIN CONDITION, YOU CAN'T HAVE TAKEN PARTICULAR DRUGS. SO THOSE ARE THE INCLUSION, EXCLUSION CRITERIA FOR YOUR STUDY, SO, YOU'VE HEARD A BIT ABOUT THIS, YOU WILL HEAR MORE WHERE IF YOU LOOK AT THE HISTORY OF CLINICAL RESEARCH AND ALSO RESEARCH ETHICKINGS, A LOT OF WHAT WE DO WAS STARTED IN RESPONSE TO WORRIED AND RESPONSE TO SCANDALS AND IN RESPONSE TO WHAT WERE REGARDED AS ABUSES, SO TUSK EAGEE PEOPLE HEARD ABOUT, A LOT OF WORK WAS DONE ON PRISONERS AND GIVEN THE HISTORY, INITIAL FRAME FOR THINKING ABOUT RESEARCH ETHICS WAS VERY MUCH ON THE SIDE OF PROTECTION, OF PROTECTING PEOPLE FROM RISKS AND WHAT THAT LED TO IN A LOT OF CASES WAS WELL, THE BEST WAY TO PROTECT SOMEBODY FROM THE RISK OF RESEARCH IS TO NOT LET THEM IN THE RESEARCH IN THE FIRST PLACE. IF YOU CAN'T ENROLL IN THE STUDY THEN YOU CAN'T BE HURT BY THE PROCEDURES IN THE STUDY, SO THERE WAS A LOT OF EMPHASIS ON PROTECTIONING SUBJECTS AND EXCLUDING THEM SO REALLY AN EMPHASIS ON THE EXCLUSION CRITERIA OF A STUDY. THAT STARTED TO CHANGE IN THE 1980S WHEN WE HAD THE HIV EPIDEMIC IN THE U.S. AND AT LEAST INITIALLY, THERE WEREN'T ANY PROVEN EFFECTIVE TREATMENTS FOR HIV AND THE ONLY CHANCE SOME PEOPLE HAD FOR GETTING ANY TREATMENT WAS IN THE CONTICKET OF A CLINICAL TRIAL. PEOPLE SEE IF THERE'S GREAT PHOTOS OF PROTESTS OF SMOKE GOING OFF AND PROTESTING AND THE POLICE CAME IN AND INTERESTINGLY THOSE PROTESTS WEREN'T THAT RESEARCH WAS RISKY AND PEOPLE SHOULD BE EXCLUDED FROM IT, THAT WASN'T THE WORRY. THE WORRY WAS THAT PEOPLE WERE EXCLUDED TOO MUCH AND THEY WEREN'T GETTING THE OPPORTUNITY TO GET TREATMENTS FOR THEIR HIV. SO THIS HAS LED TO A WHOLE SEE CHANGE IN HOW PEOPLE THINK ABOUT THIS TOPIC LATER THIS' A NUMBER OF AND RESPECT TO BREAST CANCER RESEARCH WHERE THE EMPHASIS IS ACCESS RATHER THAN PROTECTION. SO THIS IS BY LESLIE AND JIM IN THE TEXTBOOK FOR THIS SESSION, THIS LED TO PROTECTION AND FAIR ACTS ALLOWING PEOPLE TO GET INTO TRIALS. SO THESE--I WILL HAVE A COUPLE OF THESE ARROWS SO THIS IS THE FIRST 1, THESE ARE AND THE ANSWER, SO, EXISTING REGULATIONS FOR RESEARCH INCLUDE SPECIAL PROTECTIONS IN THE U.S. REGULATIONS FOR CHILDREN, FOR PRISONERS AND FOR FETUSES AND PREGNANT WOMEN AND 2 A LARGE EXTENT YOU COULD ARGUE THAT THOSE REQUIREMENTS WERE INFORMED BY THE PRIOR VIEW, OF RESEARCH ETHICS WHERE THE EMPHASIS WAS ON PROTECTION AND SO, I THINK THERE'S AN IMPORTANT QUESTION NOW AND YOU'LL GET A LITTLE BIT OF THIS, YOU'LL BE LUCKY TO HEAR FROM MAGY A LITTLE IN A COUPLE OF WEEKS ON RESEARCH WITH PREGNANT WOMEN AND THERE'S A QUESTION ABOUT WHETHER OR NOT THOSE REGULATIONS SHOULD BE REVISED, WHETHER OR NOT THEY'RE TOO STRICT OR TOO MUCH EMPHASIS ON PROTECTION. OKAY, SO THE FIRST THING WE WANT TO DO IS DISTRIBUTE THE BENEFITS AND BURDENS OF STUDIES FAIRLY, AND SO THE WAY I THINK ABOUT THIS IS ASSUME AT THE BEGINNING THAT EVERYBODY CAN GET INTO YOUR TRIAL. YOU'RE PROPOSING A NEW CLINICAL TRIAL AND START WITH THE AWRVETIONZ SUSMGZ THAT EVERYBODY'S ELIGIBLE AND THEN--ASSUMPTION THAT EVERYBODY'S ELIGIBLE AND THEN ONLY EXCLUDE PEOPLE IF HAVE YOU A GOOD REASON TO EXCLUDE THEM. SO 1 OF THE GOOD REASONS, WELL, OBVIOUSLY THE FIRST 1 IS JUST THE SCIENCE. WHAT ARE YOU DOING AND WHO DO YOU NEED IN THE TRIAL TO ANSWER YOUR PRIMARY END POINT. SO IF IT'S A TREATMENT FOR DIABETES, YOU NEED PEOPLE WHO HAVE DIABETES. SO INCLUDE PEOPLE WHO HAVE DIABETES, INCLUDE EVERYBODY ELSE. SO IT'S THE VALUE OF THE STUDY, AND ALSO THE VALIDITY MAKING SURE THAT YOU CAN GET THE STUDY COMPLETED IN TIME. SO AS I MENTIONED THE EMPHASIS ON GENERALIZABILITY, EXAMPLE I GAVE BEFORE WAS POSSIBILITY OF EXCLUDING PEOPLE WERE VERY SICK AND THE THOUGHT IS MORE POPULATIONS YOU GET INTO YOUR STUDY, IF YOU DO ANALYSIS ON THEM, YOU LEARN MORE ABOUT HOW THE INTERVENTION OR THE DRUG IN QUESTION EFFECTS DIFFERENT POPULATION, SO THIS IS AT LEASTS 1 REASON TO TRY TO RECRUIT AS BROADLY AS POSSIBLE. SO INSURING THE VALUE OF THE STUDY, AS I MENTIONED OBVIOUSLY YOU NEED PEOPLE WHO HAVE THE CONDITION. YOU ALSO MIGHT NEED TO EXCLUDE PEOPLE WHO HAVE CONDITIONS WHICH WILL INTERFERE WITH ASSESSMENT OF THE DRUG IN QUESTION, SO FOR INSTANCE ACCIDENT PEOPLE HAVE CERTAIN BRAIN TUMORS OR BRAIN TUMORS IN CERTAIN PARTS OF THEIR BRAIN, TEND TO HAVE SEIZURES, YOU CAN'T TELL IF IT'S THE RESULT OF THE BRAIN TUMORROR A RESULT OF THE DRUG YOU'RE GIVING THEM AND DID YOU'RE TESTING THE SAFETY OF THE DRUG, THAT CAN BE AN IMPORTANT CONFOUNDER AND THEN EXCLUDE PEOPLE WHO HAVE THOSE BRAIN TUMORS. HERE'S A DILEMMA THAT PEOPLE WHO PARTICULARLY STUDY RARE DISEASES FACE A LOT. HAVE YOU A NUMBER OF DIFFERENT TRIALS BUT YOU HAVE A SMALL POOL OF ELIGIBLE SUBJECTS FOR THOSE TRIALS. SO, WHAT I WAS SAYING IS BASICALLY YOU ALLOW INTB INTO YOUR TRIAL WHO SATISFIES THE INCLUSION, ANYBODY WHO CAN HELP YOU ANSWER THE QUESTION, BUT WHAT IF YOU HAVE 2 TRIALS, YOU DON'T HAVE ENOUGH PEOPLE FOR BOTH TRIALS. IS IT OKAY FOR SAY THE NIH OR RESEARCH CONSORTIUM TO SAY, WE WILL EXCLUDE PEOPLE FROM TRIAL A BECAUSE WE'RE PRIORITIZING TRIAL B AND WE WANT TO FUNNEL THEM BASICALLY TO TRIAL B OR IS THAT A DECISION THAT THE POTENTIAL SUBJECT SHOULD GET TO MAKE. IS IT FAIR TO EXCLUDE THEM OR NOT. SO ENHANCING VALIDITY. YOU WANT PEOPLE IN THE TRIAL TO ANSWER YOUR QUESTION, AND THEN, YOU HAVE A NUMBER OF PROCEDURES, REQUIREMENTS, CLINIC VISITS FOR YOUR TRIAL, SO, IF YOU ARE GOING TO GET THE DATA, PEOPLE HAVE TO DO THOSE THINGS, THEY HAVE TO UNDERGO MRIs, THEY HAVE TO UNDERGO CLINIC VISITS, ANSWER SURVEYS, SO THAT RAISES QUESTIONS ABOUT WHAT DO YOU DO, SO 1 OF THE CONSULTS WE OFTEN GET ARE QUESTIONS ABOUT WHAT DO YOU DO WITH SOMEBODY WHO MISSES 1 OF THEIR SCANS. THEY MISS AN APPOINTMENT SO IT'S A TREATMENT TRIAL, SO IT'S BENEFICIAL FOR THAT PERSON, BUT YOU'RE NOT GETTING AS GOOD A DATA AS YOU COULD IF THEY MET THE REQUIREMENTS. AT WHAT POINT IS IT FAIR TO SAY, WE WILL DROP YOU OUT OF THE STUDY, WE'RE NOT GETTING SUFFICIENTLY USEFUL DATA FROM YOU TO CONTINUE. SO MINIMIZING RISKS SO HERE'S A STANDARD VIEW PEOPLE HAVE IN RESEARCH, IRBs DO THIS ALL THE TIME WHICH I ADMIT YOU HAVE THE POOL OF EVERYBODY WHO'S ELIGIBLE, FIND OUT WHO CAN ANSWER YOUR SCIENTIFIC QUESTION, EXCLUDE THE OTHERS. NOW HAVE YOU A SMALLER POOL, AND NOW WHAT YOU DO IS ASK, HOW RISKY IS BEING IN THIS STUDY TO THE PEOPLE IN THIS REMAINING POOL IN PARTICULAR ARE THERE SOME PEOPLE WHO PHASE MUCH HIGHER RISKS THAN OTHER PEOPLE DO WHO ARE ELIGIBLE. EXCUSE ME. SO FOR EXAMPLE, THIS IS A STANDARD MOVE IN PHASE 2 TRIALS. IF YOU HAVE A DRUG THAT'S CLEARED BY THE KIDNEYS, YOU MIGHT EXCLUDE PEOPLE WHO HAVE POOR KIDNEY FUNCTION WITH THE IDEA THAT THEY WON'T EXCRETE THE DRUG AS QUICKLY, THE DRUG WILL BUILD UP IN THEIR BODIES AND THEY ARE LIKELY TO HAVE MORE EFFECTS IN TOXICITY AS A RESULT OF THAT DRUG. SO IRBS IN A CASE LIKE THAT THEY HAVE A THRESHOLD, FOR KIDNEY FUNCTION AND IF IT'S GERONTOLOGYSTS LOW THAT THRESHOLD, YOU WILL BE EXCLUDED FROM THE STUDY. ONE OF THE CONTROVERSIAL QUESTIONS THAT MAGY WILL ADDRESS FOR YOU IN A COUPLEEM OF WEEKS IS SO GIB THAT PRINCIPLE DOES THAT SUGGEST WE SHOULD EXCLUDE PREGNANT WOMEN FROM SOME TRIALS, MOST TRIALS, ALL CLINICAL TRIALS. MOST PEOPLE, RISKS IF YOU HAVE A FETUS YOU HAVE MORE RISKS IS THAT A REASON TO EXCLUDE WOMEN FROM THOSE TRIALS AND LET MAGGIE ANSWER THAT FOR YOU. HERE'S A PHILOSOPHICAL POINT I WANT TO MENTION, AS I MENTIONED HERE IT'S STANDARD PRACTICE WHO EXCLUDE PRACTICE WHO DON'T HAVE SUFFICIENT KIDNEY FUNCTION BUT NOTICE IN SOME CASES WHEN THEY HAVE A CONDITION FOR WHICH THEY DON'T HAVE EFFECTIVE TREATMENT, BEING IN A TRIAL MAY STILL NONETHELESS BE IN THAT PERSON'S MEDICAL INTEREST EVEN THOUGH THEY FACE GREATER RISKS THAN SOMEBODY ELSE. THE POTENTIAL BENEFIT OF RECEIVING THE DRUG MAY STILL OUTWAY THE RISKS FOR THEM EVEN THOUGH THE RISKS FOR THEM ARE GREATER THAN THE RISKS FOR SOMEBODY ELSE. AND THEN THE QUESTION IS, HOW DO WE JUSTIFY IN THOSE CASES, THE PEOPLE WHO EXCLUDE HIGHER RISK. WELL IT LOOKS LIKE WE CAN'T JUSTIFY IT BASED ON THEM SINCE IT'S STILL IN THEIR INTEREST TO BE IN THE STUDY. SO HERE'S WHAT SEEMS TO BE THE PLAUSIBLE JUSTIFICATION FOR THIS PRETTY STANDARD PRACTICE WHICH IS THAT, WE DON'T CARE JUST ABOUT PROTECTING INDIVIDUAL SUBJECTS AND MAKING SURE THAT PARTICIPATION IN TRIAL IS IN THE INTEREST OF THE SUBJECT, THAT'S IMPORTANT BUT IT'S NOT THE ONLY THING WE CARE ABOUT. WE ALSO CARE IN THE PROCESS OF DOING WERE AND IN THE PROCESS OF DOING THINGS ABOUT LEARNING MEDICAL TREATMENTS, WE WANT TO MINIMIZE THE TOTAL NUMBER OR AGGREGATE OF RISKS OR PARTICULARLY HARMS THAT WE CAUSE TO PEOPLE AND 1 WAY WE DO THAT IS BY EXCLUDING PEOPLE WHO FACE GREATER RISKS FROM BEING IN THE TRIAL. SO I THINK THIS RAISES WHAT I THINK IS IMPORTANT GENERAL POINT ABOUT RESEARCH ETHICS WHICH IS OFTEN THOUGHT ABOUT AS PROTECTING INDIVIDUAL SUBJECTS. I THINK THAT'S IMPORTANT BUT THERE'S OTHER THINGS GOING ON. ONE OF WHICH IS REDUCING OVER ALL RISKS OR OVERALL HARMS. OKAY, I WILL COME BACK TO THAT IN A MINUTE. SO ENHANCING BENEFIT, SO GOT THE PEOPLE WHO ARE IN THERE, PEOPLE WHO CAN GET TO THE TRIAL, WE ENHANCED THE BENEFITS THAT WE MACHINE MYSELFED THE RISKS OF THE STUDY, SO NOW WE WANT TO SEE WHAT CAN WE DO ABOUT BENEFIT FOR THESE SPECIFIC PEOPLE? SO THIS IS A DILEMMA WE FACED ON IRB, I SAT DOWN 15 YEARS AGO WHEN THEY FIRST DEVELOPED PROTEASE INHIBITORS FOR HIV. THEY LOOK LIKE THEY'RE PRETTY GOOD BUT THEY'RE EXPERIMENTAL TREATMENT AND THE QUESTION THE IRB FACED WAS WHO SHOULD WE ALLOW INTO IT TRIAL. ANYBODY ON HAS HIV, THAT'S 1 POSSIBILITY. ANOTHER POSSIBILITY IS TO SAY, NO, LET'S TAKE THE PEOPLE WHO HAVE HIGHER CD4 COUNT. SO PEOPLE WHO'S IMMUNE SYSTEM IS STILL RELATIVELY INFACT BECAUSE THEY WILL FACE LOWER RISKS, THEY ARE HEALTHIER, TAKING A NEW DRUG WILL LIKELY OPPOSE THE RISK TO THEM, SO LET'S FOCUS ON THEM. ALTERNATIVE APPROACH IS TO SAY, WELL, THEY'RE STILL RELATIVELY HEALTHY, WHAT WE SHOULD DO IS WE SHOULD LIMIT THIS STUDY TO THE PEOPLE WHO WERE PARTICULARLY SICK, PEOPLE WHO HAVE LOW CD4 COUNTS. PEOPLE WHO MOST NEED AN EFFECTIVE TREATMENT SO IF THIS WORKS, IT WILL BENEFIT THE MOST FROM RECEIVING IT. SO MAYBE WE SHOULD FOCUS ON THE LOW CD4 COUNT. HERE'S THE BENEFIT. IN THIS CASE, DO YOU CARE MORE ABOUT MINIMIZING THE RISKS OF THIS STUDY TO SUBJECTS OR DO YOU CARE MORE ABOUT, DO YOU THINK IT'S ETHICALLY MORE IMPORTANT ENHANCED OR INCREASED POTENTIAL BENEFIT FROM BEING IN THIS STUDY. SO I JUST MENTIONED BEFORE ABOUT AGGREGATE BENEFITS AND RISK, SO THIS IS BASED ON A CONSULT WE'VE BEEN WORKING ON OVER THE LAST COUPLE OF YEARS SO TYPICALLY THE WAY YOU FIGURE OUT HOW MANY PEOPLE SHOULD BE IN YOUR CLINICAL TRIAL AS YOU GET SOME STATISTICIAN AND YOU SAY, HERE'S THE QUESTION I WANT TO ANSWER, HOW MANY PEOPLE DO I NEED TO ENROLL IN MY STUDY TO ANSWER THAT QUESTION, THE STATUS--SO FOR A PHASE 1 STUDY, FOR INSTANCE THE STATISTICIAN MIGHT COME BACK AND SAY, YOU NEED TO ENROLL 8. EIGHT PEOPLE TO EVALUATE THE SAFETY OF THIS DRUG IN THIS POPULATION. SO TYPICALLY WHAT WILL HAPPEN IN THIS CASE, IS AN IRB AND INVESTIGATOR WILL SAY, OKAY, WE WILL LIMIT 8 PEOPLE, THAT'S ALL WE NEED TO ANSWER THE QUESTION, WE WILL GET IN 8 AND THEN WE WILL STOP THE STUDY. STANDARD PRACTICE. WELL, IMAGINE A SITUATION IN WHICH, 1 THAT'S ONGOING TODAY IN THE CLINICAL CENTER, IMAGINE THAT THE DISEASE IN QUESTION IS A DEVASTATING DISEASE, FURTHER IMAGINE THERE ARE NO TREATMENTS FOR THE DISEASE AND THERE'S AT LEAST SOME MINIMAL REASON PERHAPS TO THINK THAT THIS EXPERIMENTAL TREATMENT MIGHT ACTUALLY HELP THE PEOPLE. AND THEN THE QUESTION IS, IF WE DON'T JUST CARE ABOUT INDIVIDUAL SUBJEBLGHTS BUT OVER ALL BENEFITS SHOULD WE SAY, OKAY FOR STATISTICAL PURPOSES WE JUST NEED A, BUT WE SHOULD INCREASE THE END TO NEARLY 12 OR 15, DEPENDING ON HOW BIG OUR POOL IS TO LET MORE PEOPLE IN AND GIVE THEM THE CHANCE FROM BENEFIT BEING AND IN THIS TRIAL. SO IS THAT A SENSIBLE THING, HELP PEOPLE GET TREATMENT OR IS THAT INFLATING CLINICAL CARE WITH RESEARCH IN AN INAPPROPRIATE WAY? OKAY, SO LAST 1 IS PROTECTING VULNERABLE SUBJECTS SO THERE'S A BIG DEBATE ABOUT WHO COUNTS AS A VULNERABLE SUBJECT, PEOPLE HAVE DIFFERENT DEFINITIONS, I WILL GIVE YOU A BRIEF 1 IN A SECOND, THE GENERAL THOUGHT IS THAT THERE'S THIS ORDER OF PREFERENCE JUST LIKE YOU SHOULDN'T ENROLL RISKY PEOPLE. PEOPLE FOR INSTANCE WITH LOW KIDNEY FUNCTION IF YOU DON'T NEED TO, THE OTHER IS THAT YOU SHOULDN'T ENROLL VULNERABLE SUBJECT FIGURES YOU DO THE TRIAL AS WELL IN PEOPLE WHO AREN'T VULNERABLE, SO THIS IS BELMONT REPORT, YOU HEARD THE GIDDING DOCUMENT FOR RESEARCH ETHICS AND THEY OWN THIS INFLUENTIAL DOCUMENT IN RESEARCH IN DEVELOPING COUNTRIES. SO THE WAY I THINK ABOUT IT IS, THEREEE A COUPLE DIFFERENT WAYS: ONE IS PEOPLE DON'T PROTECT THEIR INTEREST AS WELL AS OTHER PEOPLE AND TYPICALLY TO THE EXTENT IT'S IT IS RIGHT DEFINITION WITHIN THE CONTEXT OF RESEARCH THE WAY WE ALLOW PEOPLE TO PROTECT THEMSELVES IS BY INFORMED CONSENT. WE TELL THEM WHAT THE STUDY S&P ABOUT AND THEY DECIDE WHETHER THEY WANT TO ENROLL, WHETHER OR NOT IT'S CONSISTENT WITH THEIR CLINICAL INTEREST. SO THAT SUGGESTS 1 REALLY IMPORTANT GROUP OF VULNERABLE SUBJECT SYSTEM PEOPLE WHO CAN'T GIVE INFORM CONSENTS, PEOPLE WITH VISOR ALWAYSIMER'S DISEASE, 2 YEAR-OLDS, PEOPLE WHO'VE BEEN IN A CAR ACCIDENT AND ARE UNCONSCIENCE. NOW 1 OF THE EXAMPLES WE FACE HERE ALL THE TIME IS WE HAVE PEOPLE WHO COME TO ENROLL IN TRIALS FROM AROUND THE WORLD, THEY DON'T ALWAYS SPEAK ENGLISH ISSUE ENGLISH IS LARGELY SPOKEN IN THIS BUILDING AND FOR THE MOST PART SOMEBODY WHO DIDN'T SPEAK ANY ENGLISH WILL BE VULNERABLE IN A CLINICAL TRIAL IN THIS BUILDING BUT THAT DIDN'T MEAN YOU HAVE TO EXCLUDE THEM, CAN YOU GET THEM A TRANSLATOR, A NURSE WHO SPEAKS THEIR LANGUAGE AND ADDRESS THE VULNERABILITY FIRST. NOW OBVIOUSLY A LOT OF VULNERABILITIES YOU CAN ADDRESS, UNFORTUNATELY WE HAVEN'T YET FIGURED OUT HOW TO GET SEVERE ALZHEIMER'S DISEASE TO MAKE THEIR OWN DECISIONS AND CONSENT AND SO, THERE'S A GENERAL VIEW THAT YOU SHOULD EXCLUDE PEOPLE WHO CAN'T GET INFORMED CONSENT, THEY DON'T HAVE AS MUCH PROTECTIONS AS PEOPLE WHO GIVE INFORMED CONSENT, EXCLUDE THEM UNLESS YOU HAVE A GOOD REASON TO INCLUDE THEM. SO THEN, THE PHILOSOPHICAL ETHICAL QUESTION HERE IS WHAT COUNTS AS A GOOD REASON TO DO A STUDY IN PEOPLE WHO CAN'T GIVE INFORMED CONSENT. THE OBVIOUS 1 IS SCIENTIFIC NECESSITY SO THE EXAMPLE I'VE BEEN USING IS SEVERE ALZHEIMER PATIENT HYMER'S DISEASE, IF YOU WANT TO STUDY A NEW TREATMENT FOR SEVERE ALZHEIMER'S DISEASE, THEN YOU NEED TO GET PEOPLE WHO HAVE A SEVERE ALZHEIMER'S DISEASE, THAT'S A GOOD JUSTIFICATION FOR ENROLLING THOSE WHO KONT CONSENT. WHAT ABOUT OTHERS, I WILL LEAVE FOR PEOPLE AND MAYBE WE CAN TALK ABOUT THIS IN DISCUSSION. WHAT ABOUT LOWER RISK? WE WERE AT A CONFERENCE IN THE PHILIPPINES ABOUT 8 YEARS AGO AND I GAVE A TALK SIMILAR TO THIS AND AN INVESTIGATOR CAME UP TO ME AFTERWARDS AND STUDIED A VERY RARE NEUROLOGICAL CONDITION. HE HAD A NEW TREATMENT, HE THOUGHT IT MIGHT WORK BUT IT COULD BE RISK SCHEHE HAD A CHOICE IN DOING IT IN PEOPLE WHO HAD THE MILD DISEASE WHO BECAUSE THE BRAINS ARE STILL RELATIVELY INTACT UNAFFECTED BY THE DISEASE FACE RISKS FROM TAKING THIS DRUG, ON THE OTHER HAND HE COULD DO IT WITH PEOPLE WHO HAD THE SEVERE DISEASE, HAD INSULTS TO THEIR BRAINS AND WOULDN'T FACE AS MANY RISKS BECAUSE THEY ALREADY LOST CAPACITY IN CERTAIN AREAS OF THE BRAIN BUT AS A RESULT THEY COULD NOT GIVE INFORMED CONSENT. SO THEY FACED LOWER RISKS AND COULDN'T GIVE CONSENT AND HIS QUESTION WAS WHO SHOULD HE DO THIS TRIAL ON, WHICH IS MORE ETHICAL TO DO THIS TRIAL ON. ANOTHER EXAMPLE IS PROSPEBLGHT OF BENEFIT, WHAT IF YOU HAVE A CASE IN WHICH ENROLL NOTHING THE TRIAL OFFERS AN IMPORTANT POTENTIAL FOR CLINICAL BENEFIT THAT PEOPLE PERHAPS CAN'T GET OUTSIDE OF A RESEARCH TRIAL. SO THIS IS A STUDY THAT CAME TO OUR DEPARTMENT FROM ZEEK EMANUEL ABOUT 15 YEARS AGO NOW AND WE STILL DEBATE WITHIN OUR DEPARTMENT ABOUT WHAT'S APPROPRIATE HERE. SO YOU HAVE SOMEBODY WHO CAN'T CONSENT BECAUSE THEY HAVE--BECAUSE THEY HAVE DOWN'S SYNDROME, THEY ALSO HAVE BREAST CANCER AND YOU HAVE A NEW TRIAL FOR CHEMO THERAPY AND ANNIE THAT LOOKS PROMISING IN BREAST CANCER, THERE'S NO REASON WHY TO TEST THE BREAST CANCER DRUG, YOU HAVE TO ENROLL PEOPLE WHO HAVE DOWN'S OR CAN'T GIVE INFORMED CONSENT IN GENERAL. THAT LOOKS LIKE A REASON TO EXCLUDE THEM. BUT IS IT UNFAIR BECAUSE IT PRECLUDES THEM FROM HAVING ACCESS TO THE PENTINE REGIMENNIAL BENEFITS OF BEING IN THE TRIAL? SO HOW DO WE THINK ABOUT THIS CASE? SO AS I MENTIONED, I THINK IF THEN YOU START G >> --THAT NEED HELP AND I WANTED TO ANSWER THE PREVIOUS PERSON'S QUESTION ABOUT GOING OUT INTO THE COMMUNITY AND WE TRY HARD TO DO THAT AND WE DO GO TO HEALTH FAIRS, BUT A LOT OF IT IS JUST FUNDING AND NO 1 WANTS TO PAY FOR US TO GO OUT INTO THE COMMUNITY TO TALK ABOUT WHAT NIH DOES. >> YES, SO FINAL LESS IS: YOU HAVE TO TAKE MORE ADVANTAGE OF INGRID AND USE THEIR OFFICE TO MAKE SURE THAT WE GET THESE STUDIES DONE. [LAUGHTER] >> AND SEND HER MONEY. >> YEAH, GET HER FUNDING. TALK TO PEOPLE IN CONGRESS. INGRID NEEDS A HIGHER SALARY AND MORE FUNDING. >> OKAY, TIME FOR A BREAK. PLEASE COME BACK AT 10:30 BECAUSE WE HAVE A PANEL AFTER THE BREAK AND TELL BE VERY INTERESTING, THANK YOU. >> OKAY, AS OUR PANEL ISTS ARE BEING SEATED LET ME INTRODUCE THIS PANEL. SO SOME OF YOU FIT THE BILL AND YOU WILL SEE IF THEIR PERSPECTIVES ALIGN WITH YOURS. IN YEARS PASSED, I HAVE HAD A PANEL OF JUST RESEARCH PARTICIPANTS AND SOMETIMES HAD I HAD A PANEL OF INVESTIGATORS, IS THIS YEAR I DECIDED TO PUT SOME OF EACH ON THE PANEL SO WE GET A FLAVOR OF THE DIFFERENCES. SO I AM VERY GRATEFUL TO HAVE 4 PEOPLE ON THE PANEL. WE ACTUALLY HAD A FIFTH, A RESEARCH PARTICIPANT WHO DECIDED THIS MORNING TO GO HOME BECAUSE HER HOME IS ON THE COAST IN FLOOR FLOWER AND SHE'S WORRIED ABOUT THE HURRICANE SO THAT WAS A SMART MOVE ON HER PART. I THINK TONY WILL BE ABLE TO RELAY SOME OF THERAPY AND THOUGHTS TO YOU WHEN SHE GETS HER TURN. SO THE 4 PANELISTS IN THE ORDER THAT THEY'RE SEATED ARE DR. BILL GALL, DIRECTOR OF NHGRI, TONY JONES, ANTWONET JONES, PATIENT NEAR CLINICAL CENTER. DR. ANGELLA RESOURCESSEN THAT YOU WILL, AND NINA BURKWOTIZ, WHO IS A PARTICIPANT AND AN EMPLOYEE AND THEY WILL GIVE YOU THEIR PERSPECTIVE AND THEY ARE SELECTED PERSPECTIVES, IN 5 MACHINEUTES THEY CAN'T TELL YOU EVERYTHING THEY EVER STRUGGLED WITH IN THEIR WORK OR PARTICIPATION BUT THEY WILL GIVE YOU THE SALIENT POINTS AND THE REST OF THE TIME IS FOR YOU TO ASK QUESTIONS AND COMMENTS ON THE THINGS THEY RAISE. SO BILL, WOULD YOU LIKE TO DEBEGIN. >> SURE. I THOUGHT I WOULD JUST GIVE AN EXAMPLE. THERE'S A DISEASE CALLED PLAGEARIA, THE PREVALENCE IS LESS BECAUSE THE PARENTS DIE BY THE AGE OF 13, ON AVERAGE AND THERE MAY BE 30 PATIENTS IN THE WORLD WITH THIS AND WHAT THEY DIE OF IS VASCULAR PROBLEMS, IT'S POOR BLOOD FLOW AND THEY MAY HAVE MY O CARDIAL INFARCTION OR CNS DISEASE, AND SO 1 QUESTION WAS, BECAUSE WE HAD SOME EXPERTISE THAL, WE SAW FEN, 16 PATIENT IT IS OR SO AT THE NIH A WHILE AGO AND THERE'S A POSSIBLE TREATMENT THAT WAS RELATED TO THE MECHANISM INVOLVED HERE. BASICALLY A SMALL MOLECULE TREATMENT AND 1 QUESTION FOR US AS INVESTIGATORS AND FOR THE ADVOCACY GROUP WAS IF WE WERE TO DO A TRIAL WITH THIS, WOULD THAT TRIAL BE OPEN LABEL OR WOULD IT BE A PLACEBO CONTROL? AND THIS HAD INCREDIBLE IMPACT ON THE INDIVIDUALS WHO WERE OUR PATIENTS. THERE WERE RESEARCH SUBJECTS BUT ALSO OUR PATIENTS. AND THE PERSPECTIVE WAS THAT FROM SORT OF A SCIENTIFIC STANDPOINT, THERE WAS NOT COMPLETE CONSENSUS BUT REASONABLE CONSENSUS THAT THESE COULD BE PLACEBO CONTROL TRIALS AND THEY HAVE A MUCH BETTER CHANCE FOR THE FIELD OF PLAGERIA BUT ALSO FOR FUTURE PATIENTS. FROM THE PATIENT PERSPECTIVE THERE WAS A AN INTEREST IN RECEIVING THIS DRUG, PERIOD, WITHOUT HAVING THE POSSIBILITY OF RECEIVING THE PLACEBO, SO OPEN LABEL WAS WHAT WAS FAVORED BY AT LEAST SOME OF THE PATIENTS AND ADVOCACY GROUP. SO REALLY THIS BROUGHT UP A REPEATED AND SORT OF LONG STANDING ISSUE OF WHAT IS MY RESPONSIBILITY, AS AN INVESTIGATOR AND ACTUALLY AS A PHYSICIAN WHO HAS SOME PERHAPS DUTY TO THE PATIENTS AS WELL. AND SO, THE WAY THAT I SAW THIS, WAS THAT WE HAD 15 PATIENTS OR SO WHO MAY RECEIVE THIS DRUG AND I HAD A RESPONSIBILITY TO THEM TO SEE IF THEY COULD GET IT BUT WE DIDN'T KNOW IF THE DRUG WOULD WORK AND I THOUGHT THAT WITH THAT FEW NUMBER OF INDIVIDUALS, WE WEREN'T GOING TO KNOW IF THIS DRUG WOULD WORK WITH AN OPEN LABEL STUDY. SO, I ALSO SAW BESIDES MY RESPONSIBILITY TO THOSE INDIVIDUAL PATIENTS, I SAW A RESPONSIBILITY TO FUTURE PATIENTS WITH PLEGARIA AND HOW CAN I WEIGH THOSE 2 RESPONSIBILITIES IN HERE? BECAUSE, THERE WILL ALWAYS BE PEOPLE WHO WILL FAVOR TRYING TO GIVE EVERY PATIENT THE DRUG. THEY WILL ALWAYS BE THOSE PEOPLE WHO ADVOCATE FOR THAT. BUT IT'S A UNIQUE RESPONSIBILITY TO BE IN A POSITION TO INFLUENCE THE PEOPLE FOR THE FUTURE AND FOR THE FUTURE PATIENTS OF PLEGARIA, DO WE HAVE ANY RESPONSIBILITY FOR THAT, SO THAT'S THE QUESTION THAT I POSE HERE FOR GROUPS LIKE THIS BECAUSE IT'S ABSOLUTELY RECURRING THEME AND SOMETHING THAT WE SORT OF HAVE TO DEAL WITH. SO THAT'S WHAT I HAVE TO SAY. >> THANK YOU VERY MUCH. WE WILL LET EVERYBODY SPEAK BEFORE WE GET INTO THE DISCUSSION OF THAT BUT THAT'S A REALLY INTERESTING CASE. TONY? >> GOOD MORNING. I WILL SPEAK FIRST FOR MAUREEN, WHO IS THE PATIENT WHO DECIDED TO GO HOME AND MANAGE HER ISSUES THIS MORNING AND SHE ACTUALLY WROTE SOMETHING SHE WANTED TO SHARE SO I'M SPEAKING FOR HER. SHE SAID I WAS DIAGNOSE SAID WITH A VERY RARE DISEASE AT AGE 3, UNFORTUNATELY BECAUSE IT WAS SO RARE IT WAS DIFFICULT TO FIBBED DOCTORS TO TREAT ME. WHEN I WAS IN MY 20S, I KEPT GETTING RECURRING PNEUMONIA AND OTHER INFECTIONS THAT IMPACT SAID MY QUALITIED OF LIFE. SO I NOTICED NIH WAS DOING A PROTOCOL AND THEY GRACIOUSLY ACCEPTED ME. SINCE THEN IT HAS BEEN ALMOST 20 YEARS, THEY HAVE SAVED MY LIFE A FEW TIMES AND MOST CERTAINLY MY QUALITY OF LIFE. I WORK FULL-TIME AND LOVE WHAT I DO I CAN'T SAY ENOUGH GOOD ABOUT MY TEAM. THEY HAVE BEEN AMAZING THROUGH ALL THESE YEARS. I NEVER ONCE FELT PRESSURED TO DO ANYTHING AND THEY TREAT ME LIKE A PERSON. THEY'RE LIKE MY SECOND FAMILY, AFTER ALL THESE YEARS THEY THINK ABOUT THE BEST WISHES OF THEIR PATIENTS. THEY AREN'T ONLY FOCUSED UPON THEIR RESEARCH. I JUST GOT BACK FROM PARIS AND I COULD NONAPOPTOTIC THE HAVE DONE THIS IF IT HAD NOT BEEN FOR THEM. AND THAT'S FROM HER. AND I THINK THAT'S AN IMPORTANT PIECE TO REMEMBER AS YOU'RE DESIGNING STUDY AND YOU INTERACT WITH PATIENTS THAT SORT OF PERSPECTIVE OF THE PATIENT WHO HAS BEEN HERE AND IS SO GRATEFUL FOR WHAT THEY RECEIVED. THAT'S ALWAYS IN FRONT OF YOU, AND AS A PATIENT REPRESENTATIVE AND A NURSE BY BACKGROUND AND SOMEONE WHO'S BEEN IN THIS ORGANIZATION FOR 29 YEARS, I HAVE A UNIQUE PERSPECTIVE AS WELL, AND I TALK TO LOTS OF PATIENTS, LOTS OF CLINICIANS TO SOME OF YOU IN THE ROOM ABOUT THE INTERACTIONS THAT WE HAVE WITH OUR PATIENT AND THERE'S JUST A FEW THINGS I POINT OUT THAT I WANT TO BE AWARE OF AS YOU CONDUCT THESE STUDIES. IT SOUNDS SIMPLE BUT THIS IS A VERY OVERWHELMING TO COME TO AS A PATIENT. IT IS VERY CONFUSING TO BE HERE. EVEN THE MOST SOPHISTICATED PEOPLE ARE OVERWHELM, NOT ONLY WITH THEIR DISEASE BUT WITH NAVIGATING A PLACE LIKE THIS AND UNDERSTANDING THE EXPECTATION, THE RESPONSIBILITIES OF A RESEARCH PROTOCOL. PLEASE KEEP THAT IN THE FOREFRONT OF YOUR MIND. THIS PLACE IS VERY FRAGMENTED IF YOU THINK ABOUT THE VARIOUS DEPARTMENTS, DIFFERENT INSTITUTES DO THINGS DIFFERENT WAY AND PAIBTS LEARN ABOUT THAT BECAUSE THEY TALK ABOUT THAT FROM WEIGHTING ROOMS, IN CAFETERIAS ON THE SHUTTLE BUSES AND THEY LEARN THESE DIFFERENCES AND SOMETIMES IT FEELS UNFAIR TO THEME BECAUSE WE DON'T UNDERSTAND HOW THEY OPERATE AND WE DEPONENT ALWAYS UNDERSTAND HOW EACH OTHER OPERATES EITHER SO KEEP THAT IN MIND THAT SOMETIMES YOU'RE EXPLAINING, NOT DEFENDING BUT EXPLAINING UNIQUE DIFFERENCES WHEN THEY HEAR ABOUT THINGS PEOPLE MIGHT GET AND THEY DON'T GET AND THEY DON'T UNDERSTAND WHY. THERE'S A LOT OF INCONSISTENCIES AROUND HERE EVEN THOUGH WE DO OUR BEST, THEY DON'T ALWAYS MAKE SENSE AND LINE UP TO OUR PATIENTS. ANOTHER CONFUSION IS CLINICAL CARE VERSUS RESEARCH AND PLENTY OF OUR PATIENTS COME HERE AND THEY ARE THINGS THAT THE PROTOCOL OUTLINE THAT WE WILL TAKE CARE OF AND THERE ARE CLINICAL ISSUES THAT WE'RE ASKING THEM TO MANAGE AT HOME THAT BECOMES VERY CONFUSING AND THOSE EXPLANATIONS ARE REQUIRED ONGOING AND THOSE DECISION VS TO BE REALLY CLEAR TO THEM BECAUSE THEY CAN BE A BIT DISJOINTED. I CAN'T EVEN READ MY OWN WRITING. [LAUGHTER] I THINK THIS IS IMPORTANT, DAVID SORT OF GOT TO THIS, WE TELL OUR PATIENTS THEY'RE PARTNERS IN THEIR CARE, WE WANT THEM TO PARTNER WITH US, BUT PARTNERSHIP HERE IS VERY DIFFERENT THAN WHAT THEY MIGHT HAVE EXPERIENCED ON THE OUTSIDE. I MEAN HERE WE RELY - THEM TO PARTNER WITH US, TO TELL US THEIR SYMPTOMS, WE EXPECT IT FOR THE PROTOCOLS TO BE IN TACT, BUT IF YOU THINK ABOUT PATIENTS IN OUTSIDE HOSPITALS, THERE'S NO PARTNERSHIP GOING ON, THEY GO IN, GET IT DONE AND GO HOME. SO THE EXPECTATION OF PARTNERSHIP MAY BE FOREIGN TO THE PATIENTINGS SO ENGAGING THEM AROUND HOW IT'S IMPORTANT TO GET THE FEEDBACK AND TAKING THE FEEDBACK IN WHEN THEY PROVIDE IT TO US, IS REALLY IMPORTANT RATHER THAN BECOMING EITHER OFFENDED THEY'VE TOLD US SOMETHING WE'RE NOT DOING WELL OR PUSHING BACK, TO ENCOURAGE THAT PARTNERSHIP. THERE WERE TIMES SPENT LAST WEEK ABOUT THE INFORMED CONSENT ABOUT THE PROCESS AND I'LL JUST SAY THE WORD PROCESS OVER AND OVER AGAIN BECAUSE IT IS PART OF A JOURNEY, IT'S NOT THAT 1 SHOT, THAT FIRST DAY THEY COME AND FIND THAT YOU KNOW--WE KNOW ABOUT HUMAN BEHAVIOR, WE KNOW ABOUT PEOPLE BEING STRESSED AND OVERWHELMED AND THEY CAN ONLY TAKE IN SO MUCH INFORMATION AT A TIME AND SO THERE ARE TIMES WHEN WE TALK TO INVESTIGATORS OR RESEARCH NURSES COORDINATED TO INTERACT WITH PATIENTS FREQUENTLY AND PATIENTS SAID I DON'T UNDERSTAND THIS PART OF THE PROTOCOL OR THIS EXPECTATION AND WHEN I REACH OUT TO THOSE TEAM MEMBERS TO SAY, WE NEED TO HAVE ANOTHER CONVERSATION, WE GO BUT I TOLD THEM ALREADY, I TOLD THEM 7 TIMES. YEAH, YOU HAVE TO TELL HER AN EIGHTH TIME BECAUSE WE KNOW THAT IT'S NOT SO MUCH ABOUT WHAT YOU DIDN'T SAY, IT'S ABOUT WHAT THEY CAN TAKE IN OR EVEN WHEN THEY WERE ABLE TO UNDERSTAND IN THAT MOMENT. SO, I GUESS THE TAKE HOME MESSAGE HERE IS, INFORMING THEM IS AN ONGOING PROCESS AND BE PATIENT WITH OUR PATIENTS. BECAUSE THEY DON'T TAKE IT IN ALL AT 1 TIME AND THEY DO NEED REMINDERS AND CLARIFICATION. AND THEN THE OTHER THING I WOULD SAY IS THEY SEE THE NIH AS 1 ORGANIZATION, THEY DON'T REALLY SEE THE NCI AND THE CLINICAL CENTER AS DISTINCT. SO WHEN 1 PART OF THIS ORGANIZATION BREAKS DOWN, WE ALL BREAK DOWN. SO WHEN THERE ARE TIMES WHERE 1 DEPARTMENT DOESN'T SUPPORT WHAT THE INSTITUTE MEANS AND THE PATIENT HEARS OR SEES THINGS POINTED AT 1 ANOTHER. WE ARE THROWING OURSELVES UNDER THE BUS. WE'RE NOT LOOKING AT THE BEST INTEREST OF THAT PATIENT. SO, I GUESS I WOULD ENCOURAGE ALL OF US TO--WHEN THERE ARE THOSE BREAK DOWNS THAT WE HAVE MORE FEEDBACK TO DEPARTMENTS, TO 1 ANOTHER THAN AIRING SORT OF OUR INEFFICIENTS TO OUR PATIENTS BECAUSE THEY'RE NOT GOING TO SAY THEY WILL SAY IT'S NOT THE SURGERIES OR THE CLINIC, THEY WILL SAY IT'S NIH THAT FAILED ME, SO WE ALL HAVE A PART IN THE SMOOTH TRANSITION FOR OUR PATIENTS AGAIN I WOULD SAY, THEY SEE US AS 1. AND WHEN PEOPLE COME TO ME AND THEY HAVE A COMPLAINT ABOUT SOMETHING THAT HAS BEEN DONE, I SAY I'M SORRY ON BEHALF OF THE ORGANIZATION, WE FAILED YOU I DON'T SAY IT WAS THAT RESEARCH NURSE ORIGINAL THAT DOC, WE NEED TO FIGURE OUT HOW WE CAN MAKE THIS BETTER FOR YOU AND HOW WE CAN FOR OTHERS GOING FORWARD. ANOTHER PART I WOULD SAY OF THAT PROCESS IS AS MUCH AS CAN YOU TRY TO HELP PATIENTS UNDERSTAND, THEY ALSO HAVE RESPONSIBILITIES AS RESEARCH FACILITIES, THEY HAVE RIGHTS AND RESPONSIBILITIES DAVID TALKED ABOUT THE ETHICAL QUESTION COMING, ROUND WHEN YOU COME IN AND THEY DON'T SHOW UP OR COME IN PLEAT, WHAT DO YOU DO THEN IT'S TALKING ABOUT THEIR RIGHTS AND THEIR RESPONSIBILITIES AND FOR THEIR SAFETY HOW WE NEED FOR THEM--SO THOSE INCONSISTENCIES ARE CHALLENGING AS WELL, SO LASTLY, THE IDEA OF PREPARING FOR THE MUNDANE, MANY OF OUR PATIENTS FIND THEMSELVES ALONG THE TRAJECTORY OF OF THE RESEARCH HAVING TROUBLE BECAUSE OF THE MUNDANE THINGS LIKE TRANSPORTATION, LIKE CHILDCARE LIKE PARKING AND THEY MAY OR MAY NOT ASK YOU FOR THOSE RESOURCES SEOUR JOB SOPHISTICATED TO EXPLORE THOSE AND GET THOSE RESOURCES IN PLACE AND PAY ATTENTION TO THESE ARE WHOLE PEOPLE WITH THINGS GOING ON AND YES THEY WILL COME FOR PROTOCOL PIECES BUT THEY ALSO HAVE OTHER CHALLENGES AND WE DON'T WANT TO IGNORE THOSE EITHER. SO THAT'S ENOUGH FOR NOW. THANK YOU. >> GREAT, TONY, THANK YOU. >> DR. ROSENTHALL? I WORK FOR THE HIV/AIDS HEPATITIS E TIGHT ISOTOPE CLINICAL AIDS RESEARCH PROGRAM. I WILL EXPLAIN WHAT IT DOES BECAUSE IT'S DIFFERENT THAN WHAT WE TRADITIONALLY DO AT NIH, THE D. C. PARTNERSHIP FOR HIV/AIDS PROCESS IS A COLLABORATION BETWEEN THE OFFICE, AND THE D. C. INSTITUTES OF HEALTH AND THE NIH. IT WAS FORMED TO CREATE A MULTIDISCIPLINARY APPROACH TO COMBAT THE LEVELS OF HIV IN WASHINGTON D. C. THE TEAM OF FROM NIH MAKES UP THE SPECIALTY PILLAR OF THE PROGRAM AND WHEN IT STARTED WE WENT WENT TO PROVIDERS IN THE DISTRICT AND OVERWHELMING 3 THEY SAID THEY NEEDED HELP WITH HEPATITIS E TIGHT ISOTOPE B. AND FROM THATLET CLINICAL RESEARCH WAS BORN. IN THE U.S. 3-4 MILLION PEOPLE ARE CHRONICALLY THIS VIRUS JUST POETIC PORTIONATELY IMPACTS PEOPLE WHO LIVE IN URBAN CENTERS, AND PEOPLE WOHAVE BEEN INCARCERATED SO REALLY IN AN EFFORT TO OVERCOME AND MINIMIZE BARRIERS THAT TONY WAS TALKING ABOUT, THE MODEL THAT WAS CREATED WAS A BIT DIFFERENT SO FOR OUR CLINICAL STUDIES WE ACTUALLY BRING OUR SERVICES TO D. C. PATIENTS RATHER THAN THE TRADITIONAL MODEL, AND SO WE EMBEDDED CLINICS AND COMMUNITY HEALTH CENTERS AND MORE RECENTLY IN NONCLINICAL ORGANIZATIONS THAT ACCESS PATIENTS IN MARGINALIZED PATIENT POPULATIONS. USING THESE TRIALS WE EMBED THESE WITH INVESTIGATIONAL AGENTS AIMED AT TREATING AND OPTIMIZING TREATMENT OF HEPATITIS E C, AS WELL AS EPILEVELLATION LOOKING AT BETTER IMPROVEMENT OF TREATMENT OF HEPATITIS C. SO WE ENCOUNTERED VARIOUS CHALLENGES. I WILL SPEAK ON A FEW. ONE BIG ETHICAL CHALLENGE WE FOCUS ON A LOT IS FAIR SELECTION OF PATIENTS. RESEARCH TRIALS REQUIRE RELIABLE COLLECTION OF DATA IN ORDER FOR MEANINGFUL RESULTS TO BE PRODUCED SO THERE'S OFTEN A PRIORITY ON PATIENT WHO IS CAN BE SEEN AS RELIABLE, HAVE ACCESS TO TRANSPORTATION, FLEXIBLE WORK SCHEDULES, CARE AND ALSO PEOPLE WHO WE BELIEVE ARE ABLE TO UNDERSTAND COMPLEX OR ADJUVANTS OR COMPLEX STUDY SCHEDULES. BUT OFTEN WHAT RESULTS IS THAT WE'RE LIMITING INCLUSION OF PEOPLE WHO HAVE MEANS OR BASE LINE HEALTHCARE LITERACY. SO FOR THE TRIALS OF HEPATITIS C TREATMENT, THE RESULT IS THAT THE POPULATION IS OFTEN PREDOMINANTLY MIDDLE AGED WHITE MEN, SO OUR MODEL OF COMMUNITY ACADEMIC COLLABORATION AND EMBEDDED CLINICAL TRIAL IN THE COMMUNITY ALLOW US TO OVERCOME SOME OF THAT CHALLENGE BY MEETING PATIENTS WHERE THEY'RE AT AND ENROLLING MINORITY PARTIC PACT WHO IS ARE HAPPY TO PARTICIPATE IN RESEARCH IN THEIR PRIMARY MEDICAL HOME BUT WOULD NOT BE COMFORTABLE OR ABLE TO TRAVEL TO BETHESDA FOR A CLINICAL TRIAL. ANOTHER ETHICAL CHALLENGE WE OFTEN SEE BECAUSE WE'RE EMBEDDED IN THESE COMMUNITY SYSTEM ACTIVE STANDARD OF CARE TREATMENT. PATIENTS WITH POOR ECONOMIC STATUS CANNOT GET ACCESS TO STANDARD OF CARE MEDICAL TREATMENT. FOR HEPATITIS C WHEN THIS CAME OUT 3 YEARS AGO, MEDICATION WAS PRICED AT OVER A THOUSAND DOLLARS PER PILL FOR A 3 MONTH COURSE OF TREATMENT SO AS A RESULT INSURANCE COMPANIES HAVE PLACED RESTRICTIONS ON WHO CAN ACCESS THE MEDICATION ESPECIALLY THOSE WHO HAVE MEDICAID OR OTHER SAFETY NET INSURANCES, SO MANY THAT WE SEE, EVEN THOUGH THERE'S FDA APPROVED MEDICATION TO TREAT THEIR ILLNESS, THE CLINIC HAS THE ONLY OPTION FOR THOSE HOPING TO BE CURED FOR HEPATITIS C. SO WE FEEL LIKE THE TRIAL CAN BECOME COERCIVE BECAUSE PATIENTS HAVE NO OTHER IMMEDIATE OPTION OUTSIDE OF CLINICAL RESEARCH. ALONG THE SAME WAY, WE SEE CHALLENGE OF NONAVAILABILITY OF THE PROTOCOL SERVICES. SO DURING A PROTOCOL A SERIOUS MEDICAL FINDING UNRELATED TO THE PROTOCOL MAY BECOME EVIDENT. DURING A HEPATITIS SCREENING WE MIGHT HAVE A LIVER LESION, AND WE HAVE THE CAPACITY TO REFER PATIENTS TO SPECIALTY EVALUATION WITHOUT COST AND IN ACADEMIC INSTITUTIONS WE CAN OFTEN HAVE PATIENTS BE SEEN WITHIN THE HOSPITAL SYSTEM. BUT BECAUSE WE'RE PRACTICING IN COMMUNITY HEALTH CENTERS WE'RE NOT AFFILIATED WITH SPECIALISTS AND THEY HAVE TO BE REFERRED TO OUTSIDE INSTITUTION FOR SPECIALTY CARE. AGAIN BECAUSE A LARGE PORTION OF OUR PATIENTS ARE MEDICATE PATIENTS WHICH MEANS THAT IN D. C. THEY OFTEN DON'T HAVE ACCESS TO A LOT OF SPECIALTY CLINICS. WE ARE OFTEN LIMITED IN OUR ABILITY TO REFER PATIENTS TO TIMELY NECESSARY SPECIALTY CARE. SO IT RAISES THE QUESTION TO US ABOUT WHAT IS THE ETHICAL RESPONSIBILITY TO PROVIDE CARE WHEN AN OMINOUS FINDING IS ARKS DENTIFIED IN THE COURSE OF A STUDY BUT UNRELATED TO THE PROTOCOL AND NOT SUPPORTED BY THE STUDY 49ABLELY. ANOTHER CHALLENGE WE ARE STARTING TO SEE IS AROUND CONSENTING. STUDIES OF HEPATITIS C OFTEN INCLUDE PATIENTS WITH SUBSTANCE DISORDER, FOR 1 OFURE STUDIES, ONGOING DRUG INJECTION USE IS PART OF THE STUDY, SO THE QUESTION IS HOW DO YOU DETERMINE WHEN THE PATIENT IS CONSENTIBLE AND IS IT EVER ETHICAL TO CONSENT A PATIENT WHO MAY BE INTOXICATED THIS IS PARTICULARLY COMPLICATED BECAUSE REQUIRES SOBRIETY MAY BE ETHICAL TO THE STUDY AND WHO CAN ENROLL AS SOME PATIENTS ARE UNABLE TO ABSTAIN FROM DRUG USE. AND LASTLY, WE COLLECT EPIDEMIOLOGIC SURVEYS ASKING ABOUT PRACTICES WHICH ARE CRIMINALLY PRACTICED IN THE UNITED STATES AND IT'S OUR GOAL TO ALWAYS UPHOLD HIPAA AND MAINTAIN THEIR PRIVACY BUT WE HAVE TO TAKE INTO CONSIDERATION THAT ENDORSING THESE PRACTICES CAN PUT THEM AT RISK FOR CRIMINAL PROSECUTION AND PAROLE AND OTHER CONSEQUENCES. SO IN ORDER TO BE ETHICAL WE HAVE NOT OHM PUT MEASURES IN PLACE THAT INFORMATION IS PROTECTED BY THE PUBLIC BUT WE HAVE TO PUT IN PLACE A CERTIFICATE OF CONFIDENTIALITY TO INSURE THAT LAW ENFORCEMENT IS ABLE TO SUBPOENA INFORMATION THAT IS USED. THANKS. >> NINA? >> I'M NINNA, I HAVE BEEN AN EMPLOYEE HERE AT NHIERARCHIES H FOR 7 YEARS AND I WORKED IN RECRUITMENT FOR ABOUT 5 YEARS DURING CLINICAL OUTREACH AND RECRUITMENT FOR VACCINE CLINICAL TRIALS. I GOT MY MASTERS AND THEN SWITCHED OVER TO WRITING PROTOCOLS FOR THE CLINICAL TRIAL AND SO I'VE HAD AN EXPERIENCE BOTHOT OUTREACH AND RECRUITMENT SIDE AS WELL AS DEVELOPING ADVERTISEMENTS, PLACING THE ADVERTISEMENTS, WORKING WITHIN THE COMMUNITY AND HARD TO REACH POPULATIONS, PERHAPS HIV POSITIVE AND PRIMARILY OUR STUDIES WE DO RECRUIT HEALTHY VOLUNTEERS AND SO, I SPENT A GOOD AMOUNT OF TIME DOING RECRUITMENT AND THEN I TRANSFERRED OVER TO WORKING ON THE PROTOCOL SPECIALIST WHERE I NOW RIGHT THE PHASE 1 AND 2 VACCINE TRIALS FOR THE VARIOUS VACCINES THAT COME OUT OF RESEARCH CENTER, SO, RIGHT NOW, OUR BIGGEST STUDY IS THE ZEEKA DNA VACCINE AND THERE'S A FEW ETHICAL ISSUES THAT WE'RE WORKING THROUGH RIGHT NOW ESPECIALLY INVOLVING PREGNANCY FOR SUBJECTS WHO ARE PARTICIPATINGOT STUDY, WHAT IF THEY GET PREGNANT, WHAT IF WE--WHAT IF SOMEONE WHO IS PREGNANT THEN GETS ZEEKA BECAUSE WE'RE TARGETING AREAS WHERE ZICKA IS AN EPIDEMIC SO THAT'S IN SOUTH CENTRAL LATIN AMERICA. AND THAT'S THE EMPLOYEE SIDE I'LL TALK MORE ABOUT BUT AS A PARTICIPANT IN THE STUDY, I HAVE PARTICIPATED IN 2 VACCINE TRIALS OF THE HEALTHY VOLUNTEER AND THE FIRST WAS A MALARIA VACCINE STUDY WHERE I GOT THE MALARIA VACCINE 4 TIMES AND THEN WAS EXPOSED TO MALARIA BY MALARIA INFEBLGHTED MOSQUITOES, 2 DIFFERENT TIMES TO FIRST TEST EFFICACY AND THEN TO TEST DURABILITY. AND THEN AS A--AN NIH EMPLOYEE, I AM NOT ALLOWED TO SAY THAT I WAS PROTECTED AGAINST MALARIA BUT AS A HEALTHY PARTICIPANT, I THINK I WAS PROTECTED AGAINST MALARIA BECAUSE TWICE I WAS EVALUATED BY MALARIA BLOOD SMEARS AND I WAS MALARIA-FREE, SO I THINK AS A PATIENT I HAVE TO BE CAREFUL WHAT I SAID, BUT I HAD TO TELL MY BOSS WHEN I WAS DOING THE PRESENTATION, AS AN EMPLOYEE, I WAS NOT PROTECTED AGAINST MALARIA. AND THE OTHER STUDY THAT I'M CURRENTLY ON IS THE FACE 1 ZEEKA VACCINE STUDY. AND I HELPED EDIT THAT PROTOCOL, I DID NOT WRITE IT, BUT I DID HAVE A HAND IN EDITING IT AND I USE MOOD I BACKGROUND TO HELP WITH THE INFORMED CONSENT. --THE FASTER WE CAN GET OUR ANSWERS, WE CAN MOVE ON TO DOING BIGGER AND BETTER THINGS WITH THE VACCINES AND SO, AS I--AS AN EMPLOYEE, I NEVER--I NEVER WORKED ON THE PROTOCOL AS IF I WERE TO PARTAS PARTICIPATE IN A TRIAL, I HAPPEN TO QUALIFY AND SO, I'VE GOTTEN 1 VACCINE AND I FEEL GOOD AND I'LL GET MY OTHER VACCINE IN A MONTH AND HOPEFULLY WE WILL GET GOOD RESULTS BUT EACH TIME BEFORE I PARTICIPATED IN THE TRIAL I HAD TO UNDERGO A BIOETHICS CONSULT AND THAT'S HOW I MET DR. GRADEY WAS DURING THE CONSULT AND IN THE CONSULT IS WHEN THEY'LL TALK ABOUT A FEW ISSUES THAT I COULD SEE, COULD BE A PROBLEM, LUCKILY THEY WEREN'T FOR ME, BUT THE FIRST IS COERCION TO PARTICIPATE, DOES MY BOSS TELL ME TO PARTICIPATE, WILL MY BOSS BE UPSET IF I WITHDRAW FOR SOME REASON AND SO, I'VE NEVER FELT THAT WAY. IN FACT, I THINK FOR ME IT'S BEEN A GOOD LEARNING EXPERIENCE TO PARTICIPATE IN STUDIES AND BE ABLE TO TAKE WHAT I KNOW AS A PARTICIPANT BACK TO WRITING PROTOCOLS. AND THAT I WOULD ENQUALITY OF REVIEWAGE INDIVIDUALS TO PARTICIPATE OR NOT PARTICIPATE. ANOTHER ISSUE WAS ABOUT MY TIME. SO I TAKE LEAVE WHEN I PARTICIPATE IN THE STUDY BECAUSE I GET PAID AS A RESEARCH SUBJECT. I AM NOT PARTICIPATING BECAUSE I GET PAID ALTHOUGH THE MONEY ISN'T TERRIBLE AND AS KNOW EMPLOYEE WE ALWAYS SAY IT'S COMPENSATION FOR TIME AND INCONVENIENCE, SO I THINK THERE'S ALSO THAT--I MEAN ESPECIALLY COMING, ASKING A PARTICIPANT TO COME TO THE NIH CAN BE AN HOUR TO GET HERE AND GET ON CAMPUS AND FOR ME, I DON'T NECESSARILY HAVE THAT ISSUE, I'M HERE SO I DON'T KNOW THAT I NEED THE COMPENSATION FOR TIME AND CONVENIENCE. BUT THEY CAN'T NOT GIVE IT TO ME ETHICALLY. AND ANOTHER ISSUE, IS CONFIDENTIALITY. I UNDERSTAND GOING INTO THE PATIENT THAT MY COWORKERS THAT I WORKED WITH FOR 7 YEARS WILL SEE MY MEDICAL RECORDS AND THEY'LL KNOW WHAT MEDICATIONS I TAKE AND THEY'LL KNOW MY BLOOD COUNT AND I'M NOT A CLINICIAN. THEY KNOW ALL THOSE THINGS AND I HAVE TO DISCLOSE NEW INFORMATION AS IT COMES AND I'M COMFORTABLE WITH THAT AS WHO I AM. I'M NOT AFRAID TO SHARE THAT INFORMATION AND I DON'T FEEL LIKE I HAVE ANYTHING THAT I WOULD NEED TO HIDE FROM MY BOSS BUT I DO UNDERSTAND SHE CAN LOOK AT MY MEDICAL RECORDS AND IT COULD AFFECT HOW SHE TREATS ME OR HOW SHE MIGHT--IT COULD EFFECT HOW WE INTERACT AND IT DOESN'T AND I'M NOT WORRIED ABOUT THAT AND I DO FEEL THAT MY INFORMATION IS CONFIDENTIAL AND THAT THERE'S A LINE BETWEEN CHURCH AND STATE SO TO SAY AND 1 IS MY PERSONAL INFORMATION AND 1 IS I'M AN EMPLOYEE AND IF IT EFFECTS MY EMPLOYMENT, IF I'M SICK, THAT'S 1 THING BUT IF I HAVE TO REPORT THAT TO THE STAFF IT'S A SEPARATE ISSUE AND SO THAT'S SOMETHING THAT I THINK AS AN EMPLOYEE GOING INTO IT, YOU DO HAVE TO UNDERSTAND THAT THERE ARE ISSUES OF CONFIDENTIALITY AND ON THE SAME TIME AS AN EMPLOYEE, YOU SHOULDN'T LET THAT EFFECT YOUR WORKING RELATIONSHIP WITH ANOTHER EMPLOYEE. AND THE LAST ISSUE IS, AGAIN, WITH THE INFORMED CONSENT LIKE WE'VE DISCUSSED AND I DON'T THINK IT'S AN ISSUE. I FELT FULLY INFORMED BEFORE I PARTICIPATED BECAUSE I HAD READ THE CONSENT SO MANY TIMES BUT I ALSO WAS ABLE TO ASK QUESTIONS. THAT PROCESS WAS NOT REDUCED BECAUSE OF MY EMPLOYMENT AND BECAUSE OF MY UNDERSTANDING AND I STILL--I STILL GOT A FAIR INFORMED CONSENT PROCESS AND I FELT I WAS INFORMED AND I WAS MAKING A VOLUNTARY DECISION TO PARTICIPATE AND I'M HAPPY THAT I DID AND I AM EXCITED TO PARTICIPATE IN MORE RESEARCH AND I THINK IT'S A REALLY GOOD ASPECT FOR RESEARCHERS TO SEE THE OTHER SIDE AS A PARTICIPANT AND I WOULD SUGGEST THAT IT'S [INDISCERNIBLE]. THAT'S ALL I HAVE. >> SO FIRST JOIN ME IN THANKING THE PANELISTS FOR WONDERFUL COMMUNITIES AND AS YOU ARE LINING UP TO THE MIC'S TO ASK QUESTIONS OR COMMENT ON THE COMMENTS THAT WERE MADE IRB WANT POINT OUT A FEW THINGS THAT I THINK ARE FASCINATING. ONE IS THE RANGE OF RESEARCH THAT WE DO AT THE IN, IH. SO YOU'VE SEEN FROM A DISEASE THAT BILL WAS TALKING ABOUT THAT AS 16 PEOPLE IN THE WORLD THAT A DISEASE THAT LONA WAS TALKING ABOUT THAT HAS THOUSANDS, WE RESEARCH BOTH OF THOSE. IN VERY DIFFERENT WAYS, HOW IMPORTANT IT IS TO PUT YOURSELF IN THE SHOES OF THE PERSONS WHO ARE PARTICIPATING. CERTAINLY TONY TALKED ABOUT THAT A LOT. BUT EVEN BILL TALKED ABOUT THAT FROM THE PERSPECTIVE OF, PEOPLE WITH THIS RARE DISEASE HAVE CERTAIN EXPECTATIONS ABOUT WHAT THEY WANT WHEN THEY COME INTO A CLINICAL TRIAL AND LONA TALKED ABOUT THAT TOO, WHEN YOU HAVE OTHER KINDS OF HEALTH PROBLEMS AND YOU COME TO THE CLINIC AND GET YOUR HEPATITIS DRUGS YOU MIGHT WANT HELP WITH OTHER THINGS. I THINK IT'S REALLY INTERESTING AND I REALLY APPRECIATE NINNA BEING BEING ABLE TO DO THIS TO THINK ABOUT EMPLOYEES AS RESEARCH PARTICIPANTS. DAVE TALKED ABOUT THE IN THE LAST SESSION ABOUT VULNERABILITY, AND THERE'S AN ONGOING DEBATE ABOUT WHETHER EMPLOYEES ARE VULNERABILITY, MOST PEOPLE TEND TO THINK THEY ARE FOR THE REASONS THAT SHE SO NICELY ELUCIDATED. IN SOME SEDS, DEPENDING ON WHO YOU WORK WITH OR FOR, THERE MIGHT BE EXPLICIT OR IMPLICIT KIND OF PRESSURE TO PARTICIPATE AND THAT'S--THERE'S LOTS OF THINGS TO THINK ABOUT, ESPECIALLY IN A STUDY WITH THINGS BEING DONE THAT YOU WORK SIDE BY SIDE WITH. AND PUTTING THE SHOES OF THE PARTICIPANT IS A AN IMPORTANT WAY TO GET A SENSE OF THE KINDS OF STRUGGLES, THE KINDS OF EXPECTATIONS AND RESPONSIBILITIES THAT DO CREATE ETHICAL TENSIONS ACROSS THE BOARD. SO, PLEASE. >> I JUST WANT TO MAKE A COMMENT AND TALK MORE ABOUT THE PROTOCOL THAT YOU'RE TALKING ABOUT DISCUSSING WITH THE QUESTION OF WHETHER OR NOT YOU SHOULD DO A RANDOMIZED DOUBLE BLIND, IMINVOLVED IN A PROTOCOL THAT'S SIMILAR IN THAT WE HAVE A SMALL MOLECULE INHIBITOR, SMALL GROUP OF PATIENTS SO WE HAD PART 1 OF A TRIAL THAT WAS A DOSE FINDING ASPECT. AND SO EVERYONE, IT WAS AN OPEN STUDY. AND IT'S PRETTY OBVIOUS FROM THAT, THAT IT WORKED AND SO, THE--THE DRUG--IT'S A DRUG COMPANY STUDY, SO THEY WERE ABLE TO DO AN EXTENSION BECAUSE THE PATIENTS DID RECEIVE BENEFIT, SO ALL THOSE PATIENTS WILL NOW BE ABLE TO RECEIVE THE DRUG AND GO FORWARD. HOWEVER, THERE'S PART 2 OF THE STUDY AND IT IS GOING TO BE AIAN BLINDED RANDOMIZED TRIAL AND PART OF THE--PART OF THE PROTOCOL DESIGN IS SO THAT THE PATIENT, IF THEY RE--OR IF THEY STOP THE STUDY FOR SOME REASON, IF THEY DECIDED THEY DON'T WANT TO PARTICIPATE, THEY WILL NOT BE ELIGIBLE FOR THE CONTINUED TREATMENT AND I HAVE--I BROUGHT UP AN ETHICAL QUESTION WITH THE DRUG COMPANY ABOUT THAT BECAUSE BECAUSE IF A PERSON IS IN THE ARM THAT DOES NOT IN THE ARM THAT DOES NOT GET THE DRUG AND THEY HAVE TO DRAP OUT BECAUSE OF PROBLEMS WITH AES OR THEN THEY WOULD NOT BELIGIBLE AND THEY COULD MISS THE EFFECTS OF THE DRUG FOR YOU KNOW SOMETIME MY HOPE IS THAT THE DSMB IS INVOLVED, BUT IF IT SHOWS THERE ARE POSITIVE EFFECTINGS IN THE DRUG, THEN IT WILL BE ABLE TO THEY WILL SAY THIS DRUG SHOWS IT WORKS IN OTHER SITUATIONS. SO I'M WOBDERRING IF THAT SAME THING COULD HAPPEN IN YOUR STUDY, THAT THE DSMB WOULD SAY, YOU KNOW, IT IS SHOWING POSITIVE EFFECTS. AND WE WILL MAKE IT AVAILABLE FOR ALL PATIENTS. >> WELL, DSMBs ALWAYS RECEIVE REALTIME REPORTS AND THEN THEY ADVISE THE INSTITUTIONAL REVIEW BOARD AND SO ALL THOSE THINGS WOULD GENERALLY HAPPEN, THEY'RE INTERIM ANALYSIS AND THINGS LIKE THAT. DRUG COMPANIES OF COURSE, ARE NOT LET'S SAY FORMERLY BOUND BY THE A LOT OF ETHICS INVOLVED HERE SO WE DON'T ALWAYS SEE WHAT WEED LIKE TO SEE IN THESE THINGS. SO THERE ARE A COUPLE OF OTHER IF YOU HAVE HISTORY THAT YOU KNOW THE OUTCOME IN EVERY PATIENT WITH THIS PARTICULAR DISEAREDDER THEN THERE ARE TIMES WHEN THE NATURAL HISTORY WILL BE EVEN TAKEN BY THE FOOD AND DRUG ADMINISTRATION AS EVIDENCE AND THE SECOND ISSUE DEPENDS UPON THE EXTENT OF THE BENEFIT THAT ACCRUES BY TAKING THE DRUG, SO IF THERE'S A SLIGHT DIFFERENCE THEN YOU DO THE PLACEBO CONTROL TRIAL BUT IF THERE'S A HUGE DIFFERENCE WITH WHAT WE CALL THE LASEROUS EFFECT AND YOU GET UP AND WALK AND NEVER WALKED BEFORE, THINGS LIKE THAT CAN INFLUENCE HOW YOU DESIGN A TRIAL LIKE THIS. BUT ALL OF THESE ARE GEARED TOWARD DRUG COMPANIES INVOLVED TOWARDS NEW DRUG APPROVAL AND THE FOOD AND DRUG ADMINISTRATION, SO, THE FDA ACTUALLY HAS SOME INFLUENCE OVER WHAT PEOPLE CONSIDER ETHICAL. BECAUSE THERE'S ETHICAL ELEMENT AND FOR OTHER PEOPLE OR NOT HAVING IT APPROVED TO PEOPLE OUTSIDE THE STUDY. SO THAT'S SOMETHING PEOPLE HAVE TO CONSIDER AS WELL. NOT SURE I ANSWERED YOUR QUESTION EXACTLY. IS THERE SOMETHING STILL REMAINING. >> I JUST WONDERED IF--HOW LONG IN YOUR CASE IF THERE'S A TRUE BENEFIT IF YOU START WITHOUT WITH A RANDOMIZED CONTROL TRIAL, WILL THERE BE AN INTERIM ANALYSIS AND IF THERE IS A BENEFIT THEN YOU WOULD BE ABLE TO MAKE IT AVAILABLE TO ALL YOUR PATIENTS. YES, SO ESSENTIALLY WHEN WE HAVE TRIALS LIKE THAT, WE DO WRITE INTO THAT AND INTERIM ANALYSIS WHICH USES UP SOME OF THE P-VALUE BY THE WAY. BUT YOU CAN'T DO A NUMBER OF INTERIM ANALYSIS, BUT YOU CAN DO SELECTED--LET'S SAY POINTS THAT ARE SELECTED A PRIORI AND PRETTY MUCH RANDOMIZED PLACEBO CONTROL TRIALS DO HAVE SUCH AN INTERIM ANALYSIS AND IT'S A DSMB THAT'S SUPPOSED TO BE NEUTRAL THAT LOOKS OVER THOSE DATA, GENERALLY IN A--IN A BLINDED FASHION BUT SOMETIMES IN AN UNBLINDED FASHION WHEN ADVERSE EVENTS ARE INVOLVED. I THINK THERE'S INTERESTING ATTENTION THAT BILL ALLUDED TO THAT WASN'T EXPLICITLY DESCRIBED BUT WHEN YOU'RE AN PHYSICIAN AND INVESTIGATOR YOU HAVE 2 IMPORTANT ROLES THAT SOMETIMES CONFLICT. AND IT DOES COME TO A HEAD SOMETIMES IN THE CONDUCT OF TRIALS WHERE YOU'RE TRYING TO TEST THINGS THAT HAVEN'T BEEN TESTED BEFORE. BECAUSE YOU MIGHT BE A DOCTOR, YOU MIGHT KNOW THE PATIENT'S--THE PATIENT AND PATIENTS MIGHT COME EXPECTING THAT YOU'RE GOING TO DO SOMETHING FOR THEM, AND YET THERE'S A NEED TO DO A RIGOROUS SCIENTIFIC STUDY TO SHOW WHETHER OR NOT WHATEVER IT IS YOU'RE TEST SUGGEST SAVE AND EFFECTIVE. COMES UP OVER AND OVER AND OVER AGAIN. THERE WAS HUGE DEBATE FOR EXAMPLE LAST YEAR ABOUT EBOLA TRIALS ALONG THESE LINES AND SOME OF THE PEOPLE THAT I THINK STRUGGLE THE HARDEST WERE THE CLINICIANSOT GROUND WHO HAD TO FACE THE PATIENTS EVERY DAY AND YOU KNOW OFFER THEM A STUDY, PARSE TISIPATION AND STUDY, I THINK--PARTICIPATION AND STUDY. IT ALSO RAISES QUESTIONS THAT ELEANA RAISED AND A PERSON WHO HAS FEW OPTIONS FOR GETTING THE KINDS OF TREATMENT THEY THINK THEY NEED TO JOIN A CLINICAL TRIAL, MOST FROM THEIR PERSPECTIVE BE THE BEST OPTION. AND IN SOME CASES THAT PERCEPTION, I THINK IS ACCURATE BUT IN OTHER CASES IT MIGHT NOT BE. AND IT SHORT OF RAISES, IF YOU WANT TO SAY MORE ABOUT IT, IT RAISES THINGS MAUREEN SAID IN HERE STATEMENT BECAUSE SHE HAD A RARE DISEASE THAT NOBODY KNEW ANYTHING ABOUT, CAME HERE, HOPING THAT SHE WOULD GET YOU KNOW HELP AND SHE ACTUALLY DID AND WHAT IF SHE CAME HERE WANTING TO GET HELP AND PRESENT WIDE AN OPPORTUNITY THAT SHE DIDN'T LIKE AND THE STUDY WASN'T WHAT SHOO WAS LOOKING FOR, AND SHE WAS RANDOMIZING AND/OR WHATEVER. I WONDER IF ANYBODY COULD SAY MORE ABOUT YOU KNOW HOW DO YOU THINK ABOUT THE OPTION FROM A PERSPECTIVE OF THE PARTICIPANT ESPECIALLY UNDERSTANDING THAT THERE IS FOR SCIENCE AND GET ANSWERS TO YOU KNOW PEOPLE BEING TREATED IN THE WORLD GET THINGS WE KNOW WORK. ANYBODY WANT TO SAY ANYTHING ABOUT THAT? >> I JUST WANT TO COMMENT ON THAT AND JUST AS I WAS READING AND COMMENTING THIS MORNING, SHE SOUNDS LIKE MANY PATIENTS THAT SAY, THEY DON'T HAVE A CHOICE, THIS IS ALL THERE WAS. I'VE BEEN LOOKING FOR YEARS, I'VE BEEN SEARCHING AND YOU WILL HAVE IT AND SO THE CHALLENGE FOR THOSE OF US TREATING THE PATIENTS PARTICULARLY IN EVEN EXPLAINING SORT OF RISKS AND ALTERNATIVES OF THESE PROTOCOLS AND I THINK IT WAS DAVID MENTIONED BEFORE, THE PATIENT GOES, OKAY, YEAH, I HEARD WHAT YOU SAID BUT PSIGN ME UP. OR PEOPLE WHO CALL--BUT SIGN ME UP. OR PEOPLE WHO CALL ME AND SAY, I SIGNED THE CORN SENT WHO DO I SEND IT TO. WE DON'T WANT YOU TO SIGN ANYTHING AT HOME, COME IN, HAVE A CONVERSATION BUT UNDERSTAND THERE ARE BARRIERS THAT CHALLENGE PEOPLE WHO HAVE IN THEIR OWN LIVES DETERMINED, NIH IS MY ONLY HOPE SO THE BURDEN IS ON US TO HAVE CLEAR CONVERSATIONS AND FEEL AS CONFIDENT AS WE CAN THAT IN FACT THEY MAY WALK AWAY GOING, YEAH, I CAN QUIT WHEN I WANT, BUT I'M DOING THIS. AND ENENCOURAGING THEM TO BE AS OPEN AND TRANSPARENT ABOUT SIDE EFFECTS, THAT COME UP USING THOSE PATIENTS MIGHT REDUCE TELLING US THESE THINGS BECAUSE OF THEIR CONCERN THAT THIS IS ALL THERE IS. I MEAN THAT'S OUR DAILY DILEMMA WORRY PATIENTS LIKE THIS. I DON'T KNOW IF THAT WAS HELP BUT IT'S SORT OF REALITY. >> YEAH, THE POINT ABOUT BEING A CLINICIAN IS INTERESTING WITH ME BECAUSE AT OUR CLINICS IN D. C. WE PROVIDE CARE, STANDARD OF CARE, HEPATITIS C RESEARCH AND SO WHEN I SEE PATIENTS I AM EVALUATING FOR EITHER OR BOTH OR 1 OR THE OTHER. SO A LOT OF TIMES I'M IN THE POSITION WHERE SOMEONE REFERS TO AS A INFECTIOUS DISEASE SPECIALIST AND I'M TALKING TO THEM ABOUT THEIR OPTIONS AND WE HAVE THE OPPORTUNITY TO PROVIDE THEM CLINICAL RESEARCH AS WELL BUT IT SEEPS A LITTLE--I ALWAYS WISH THERE WAS SOMEONE ELSE WHO COULD PROVIDE AN OBJECTIVE PERSPECTIVE WHO'S NOT A PARTICIPANT OR AN INVESTIGATOR IN THE RESEARCH BECAUSE EVEN THOUGH I FEEL LIKE I'M LOOKING OUT FOR THE BEST INTEREST OF THE PATIENT AND I ALWAYS GIVE THEM THE OBJECTIVE DATA THAT I HAVE, YOU KNOW YOU ALWAYS WONDER IF THERE ISN'T A PART OF THAT YOU IS INCLINED TO ENCOURAGE PATIENTS TO PARTICIPATE IN RESEARCH EVEN IF YOU THINK THE RESEARCH IS THE BEST THEN FOR THEM, THEY THINK IT IS, IT'S HARD WHEN YOU WEAR ALL OF THOSE HATS AND PROVIDE ALL OF THOSE SERVICES FOR THEM. THE REALITY FOR A LOT OF THE PATIENTS THAT WE SEE THOUGH IS THAT WE ARE PROVIDING MEDICATION THAT THEY SHOULD HAVE THROUGH INSURANCE BUT DON'T BECAUSE OF VARIOUS INSURANCE CHALLENGES AND SO, FOR A LOT OF OUR PATIENTS RESEARCH, IS THE ONLY WAY FOR THEM TO GET ACCESS TO LIFE SAVING MEDICATION AND WE JUST HOPE THAT WE'RE DOING THE BEST FOR THEM AND THAT THAT FULLY UNDERSTAND ALL OF THEIR OPTIONS. THE CHALLENGE IS THAT THEY DON'T HAVE MORE OPTIONS FROM STANDARD OF CARE INSURANCE. , -- >> QUESTIONS OUT THERE? COMMENTS? >> IF KNEW A DRUG WORKED WE WOULDN'T DO A TRIAL BUT THERE ARE TIME WHEN IS THE PATIENT BELIEVES THE DRUG WILL WORK AND WE DON'T KNOW. SO WE HAD A CASE FOR EXAMPLE WITH PREFEDADONE WHERE WE RANDOMIZED THE PATIENTS AND--LET'S SAY THIS WAS NOT DOUBLE BLIND. AND THE PATIENT KNEW HE WAS RANDOMIZED TO THE STANDARD OF CARE WHICH WAS STEROIDS AND AS SOON AS HE FOUND THAT OUT, HE LEFT THE STUDY. SO THIS--THIS WAS, YOU KNOW SPOKE TO ME TO THE CONCEPT YOU MENTIONED ABOUT RESPONSIBILITIES OF PATIENTS, TOO. THE PERSON HAS COMPLETELY THE RIGHT TO DO THAT BUT THERE WAS AN UNDERSTANDING AND ACTUALLY COMPANIES UNDERSTAND THIS IN A WAY, TOO, BECAUSE THEY WRITE IN SOMETIMES THEIR PROTOCOL THAT ONCE PATIENTS COMPLETE THE STUDY, IF THERE'S ANY INDICATION OF SOME BENEFIT OF THAT DRUG, THEN THEY WILL RECEIVE THE DRUG, OPEN LABEL AFTERWARDS REGARDLESS IF THEY WERE RANDOMIZED TO THE TREATMENT OR PLACEBO. SO THERE'S RECRUITMENT THROUGH ALL OF THIS. THAT'S A FAIR WAY TO HANDLE THIS AND IT REALLY HURTS THE PROTOCOL TO HAVE A PERSON SORT OF SIGN UP AND THEN LEAVE IMMEDIATELY AS IF THE PERSON DOESN'T GET WHAT HE WANTS. >> YES. >> SO I'M HOPING PEOPLE WILL COME UP TO THE MIC, BUT I WILL ASK ANOTHER QUESTION UNTIL YOU DO. ONE THING IS FAIRNESS, FAIRNESS IN HOW PEOPLE ARE SELECTED, I THINK ELEANA SPOKE ABOUT PEOPLE WHO ARE SUBSTANCE INTOXICATED OR PEOPLE WHO WON'T BE RELIABLE PARTICIPANTS MIGHT BE EXCLUDED FROM A STUDY BECAUSE OF THOSE CONCERNS WHICH HAVE LEGITIMATE BASIS BUT THE QUESTION THAT I WILL POSE AND ACTUALLY I WILL LOVE FOR THESE IN THE AUDIENCE AS WELL, ARE THOSE REASONABLE, ARE THOSE FAIR REASONS TO EXCLUDE PEOPLE? I WOULD ASK NINNA TOO BECAUSE THERE ARE SOME INSTITUTIONS THAT EXCLUDE DE FACTO EMPLOYEES FROM PARTICIPATION. AND THE INTRA MURAL NH HAS NOT TAKEN THAT PROTECTION WHICH YOU DESCRIBED NICELY SO I GUESS THE QUESTION IS, YOU THINK IT'S FAIRER TO INCLUDE OR EXCLUDE THESE WHO HAVE THESE KINDS OF CHALLENGES? LIKE THEY MAY BE VULNERABLE BECAUSE THEY WORK HORMONE OR THEY MAY BE VULNERABLE BECAUSE THEY'RE INTOXICATED OR THEY MAY BE VULNERABLE BECAUSE--MAYBE VULNERABLE IS NOT THE RIGHT WORD. MAYBE THEY'RE NOT RELIABLE IN TERMS OF COMING TO THE CLINIC. ANYBODY WANT TO SPEAK TO THAT, EITHER ON THE PANEL OR IN THE AUDIENCE? >> FROM THE EXPERIENCE OF HAVING DONE CLINICAL TRIALS IN THE CLINICAL AS WELL EMBEDDED IN THE HEALTH CENTER SO 1 THING I THINK FOR SURE IS THAT IT'S ALMOST IMPOSSIBLE TO PREDICT WHO WILL BE A GREAT PATIENT. THERE ARE SOMETIMES, YOU NEED THEM TO TAKE THE MEDICATION AND THOSE ARE PEOPLE YOU SEE EVERY VISIT AT A CALL WHENEVER THERE'S AN ISSUE, AND THERE'S OTHER PEOPLE THAT ARE HERE, NICE, RELIABLE PERSON AND THEY CALL EVERY OTHER WEEK AND SAY, SORRY I FLEW OFF, I'M ON THIS BUSINESS TRIP, I WENT TO GET MEDICATION. SO THE BIG THING WE HAVE TO BE CAREFUL OF AND MAKING ASSUMPTIONS ABOUT WHAT MAKES THEM A GOOD PARTICIPANT, SO JUST BECAUSE YOU'RE NOTED ABLE TO BE THERE DOESN'T MEAN YOU'RE NOT A GOOD PARTICIPANT. USING DRUGS OR ALCOHOL DOES NOT MEAN YOU'RE NOT A GOOD PARTICIPANT, BEING PSYCHOSOCIAL DOESN'T MEAN YOU'RE NOT A GOOD PARTICIPANT. YOU HAVE TO ADDRESS THE BARRIERS AND LIKE YOU WERE SAYING IT'S TRANSPORTATION, YOU KNOW WE GIVE THEM A BUS PASS TO GIVE THEM A HOME INTO OUR COMMUNITY BASED HEALTH CENTER, AND A PATIENT WHO'S AGROPHOBIC WILL NOT TAKE THE METRO, HE COULD JUST WALK FROM HIS HOME. SO THERE'S LITTLE THINGS THAT PATIENTS CAN BECOME A GREAT STUDY PATIENT BUT IT'S 1 THING WE DO WITH OUR PROGRAM IS SEE PAST WHAT WE TRADITIONALLY BELIEVE TO BE A GOOD PATIENT AND WE FOUND THAT WE CAN EFFECTIVELY ENROLL AND TREAT OTHER PEOPLE WHO WOULD NOTED BE ENROLLED ESPECIALLY IN THESE. >> I WOULD SAY AMEN TO WHAT YOU JUST SAID ABOUT NOT MAKING ASSUMPTIONS BECAUSE EVEN THEIR PATIENT WHEN IS THEY COME AND ASK A TON OF QUESTIONS AND THEN THEY GET PEGGED AS OH THEY'RE GOING TO BE A PROBLEM. BUT WE SAID WE WANT THEM TO PARTNER AND GET ENGAGED BUT THEN THEY ASK TOO MANY QUESTIONS SO WE MAKE ASSUMPTIONS ABOUT THAT KIND OF PATIENT AND WE HAVE TO BE MINDFUL BECAUSE I REMEMBER I WAS THIS A SESSION ONCE AND A PERSON USED A PHRASE OF HAVING A CHILD'S MIND, IN EVERY ENCOUNTER YOU GO IN LIKE A KID LIKE YOU DON'T HAVE EXPERIENCE WITH THIS PERSON AND YOU TAKE THEM WHERE THEY ARE IN THE MOMENT AND NOT MAKE A JUDGMENT BASED ON MY THE OTHER HUNDRED PATES OR WHATEVER THEY DID THAT PUT YOU IN THE MIND FRAME OF WELL, THIS IS GOING TO BE TROUBLE. THAT THAT SETS US UP, WE GET TRACKED BY THOSE THINGS AND AS MUCH AS WE CAN MITIGATE OR PULL OURSELVES BACK TO BETTER OFF OUR PAIBTS WILL BE AND THE--PATIENTS WILL AND CLINICIANS WILL BE. >> GREAT. ANYBODY ELSE WANT TO SPEAK TO THAT? IT GOES INTO HOW WE WRITE INCLUSION AND EXCLUSION CRITERIA AS WELL WHICH IS REALLY IMPORTANT. WE DON'T SPEND ENOUGH TIME PAYING ATTENTION TO THAT. >> THIS IS MORE THAN I'VE EVER TALKED. >> BEFORE I CAME HERE, I WORKED IN--I DID A LOT OF DRUG TRIALS AND SO I WAS SHOCKED WHEN I CAME HERE AND FOUND THAT THE EVERY INFORMED CONSENT, THE PORTION ABOUT EMPLOYEE PARTICIPATION, BECAUSE THAT WAS NOT ALLOWED IN MOST OF THE PROTEIN COMPLEX COTS THAT I WORKED WITH, HOWEVER, I WORKED IN THE PRACTICE WHERE THERE WAS A RESEARCH PRACTICE AND A REGULAR PHYSICIANS OFFICE SO THEY WERE--PEOPLE WHO WORKED THE NURSES, WHO WORKED IN THE PRACTICE ACCOUNT PARTICIPATE BUT JUST NOT THE PEOPLE WHO WERE INVOLVED IN THE RESEARCH ITSELF. SO BUT IT STILL BROUGHT UP QUESTION BECAUSE THEY WERE EVEN--I DON'T KNOW THEY WERE JUST AS--BEHOLDEN I GUESS TO THE PHYSICIAN AS SOME OF THEM EVEN MORE SO BECAUSE THEY SORT OF HAD TENUOUS POSITIONS, SOME OF THEM SO IT WAS AN ETHICAL CONCERN THAT WE HAD AND THE OTHER THING I WAS GOING TO SAY, IS IN SOME OF THE DRUG TRIALS I'VE DONE THAT ARE NOT RELATED, YOU KNOW THEY'RE RELATED TO ALLERGY MEDICATIONS, THEY REQUIRED A DRUG TESTING AND A SCREENING AND IF YOU DID NOT--IF YOU WERE--IF YOU DID NOT PASS THE DRUG TESTING, AND I--YOU KNOW THAT DOESN'T HAVE ANYTHING TO DO WITH THE RESEARCH BUT IT WAS JUST A PART OF THE SCREENING PROCESS ITSELF. >> AND AS YOU HEARD, SOMETIMES THE PERSON WHO IS THE SUBSTANCE USER IS ALMOST AS GOOD A PARTICIPANT AS ANYBODY ELSE BUT THERE ARE SCIENTIFIC REASONS IN SOME CASES WHERE THAT NEEDS TO BE AN EXCLUSION SO IT JUST DEPENDS ON THE PROTOCOL. >> I JUST HAVE A POINT-AFRONS A QUESTION REGARDING THE ISSUE, YOU KNOW YOU TALK ABOUT THE RARE CONDITION WITH 16 PARTICIPANTS, JUST THINKING IN SUPERBOWL [INDISCERNIBLE] PRESENT OR FUTURE, IT'S GOOD TO LEARN FROM PAST AND LOOK FOR RESPONSIBILITY OF FUTURE GENERATION BUT ISN'T MORE IMPORTANT PERHAPS TO LOOK AT CURRENT PATIENTS WE HAVE, SO CASE IN POINT WHEN MY WIFE AND I WERE AT DINNER WE ALSO ORDER EXTRA SO WE CAN HAVE LEFT OVER FOR TOMORROW AND FRIDAY AND SHE SAID STOP EATING FOR WE NEED IT FOR FRIDAY LUNCH BUT I'M HUNGRY NOW. I NEED TO EAT. [LAUGHTER] SO IS IT--IS IT ETHICAL FOR YOU TO DO A PLACEBO TRIAL OR OPEN LABEL? BECAUSE YOU WANT TO HAVE YOU KNOW SCIENTIFIC KNOWLEDGE THAT CAN BENEFIT FUTURE? ABOUT WHAT BA 15 PATIENTS WHO ARE DYING? WOULD IT BE MORE BENEFICIAL FOR THEM TO ALL HAVE AN OPEN LABEL TRIAL? THAT'S 1 POINT. THE OTHER THING, I THINK IN RESEARCH WE ALL WORK ON THE PRESUMPTION THAT EVERYBODY WANTS TO LIVE, SUPPOSING A PARTICIPANT WHO HAS SUCH A RARE DISEASE THAT PARTICIPATE NOTHING TRIAL, FOR A CERTAIN DRUG MIGHT HAVE THE ADVERSE EFFECT OF MAYBE, THE END POINT WILL BE DEATH, MAYBE THAT'S WHAT THEY WOULD LIKE TO HAVE BECAUSE IF THE NATURE MAY NOT BE LEGAL WHERE THEY LIVE, THAT'S THE ONLY WAY, MAYBE THE SIDE EFFECT WILL BE IT? SO WHAT IT THEY PARTICIPATE BECAUSE THEY WANT TO DIE? I MAY THEY NOT BE INCLINED TOO BECAUSE THAT'S THE ONLY CHANCE? IS IT ETHICAL, TO EXCLUDE THEM? >> PLENTY OF WAYS PEOPLE CAN DIE IF THEY WANT TO DIE, THAT'S NOT MY BUSINESS, I'M NOT--I'M NOT EVEN GOING TO PROMOTE PEOPLE WHO WANT TO DIE. THEY CAN TAKE CARE OF THAT THEMSELVES, AS FAR AS I'M CONCERNED BUT BUT THE ISSUE OF, LET'S SAY--DIFFERENT PEOPLE HAVE DIFFERENT OPINIONS ON THAT. I WOULDN'T LIKEN IT TO FOOD. IT'S PROBABLY BETTER IF I DON'T EAT TODAY. BUT THE ISSUE IS, THAT IF THESE MODALITIES FOR STUDYING A DRUG'S EFFICACY WERE EQUIVALENT THEN IT'S VERY CLEAR, YOU SHOULD TAKE CARE OF THE CURRENT PATIENTS TO ME; IT'S VERY CLEAR, BUT THE MODALITIES ARE INCREDIBLE LIE DISPARATE IN THAT RESPONSE. AN OPEN LABEL STUDY IS INCREDIBLY INFERIOR IN THIS CASE TO A PLACEBO CONTROLLED STUDY AND BASICALLY THE WORLD'S EXPERTS WILL AGREE TO THAT AND IN FACT, IN THIS CASE, THEY DID AGREE TO THAT. SO UNDER THOSE CIRCUMSTANCES WHAT YOU MAY END UP WITH IS NOT HELPING THE CURRENT PATIENTS AND NOT HELPING FUTURE PATIENTS. SO YOU ACTUALLY IF YOU DO AN OPEN LABEL STUDY, SO AT LEAST YOU HAVE A CHANCE OF HELPING SOME OF THE FUTURE PATIENTS AND THEN I WOULD JUST REITERATE THE POINT I MADE BEFORE, IF WE ALWAYS TAKE CARE OF THE CURRENT PATIENTS AND USE INFERIOR METHODS LIKE THAT. THEN NOBODY'S EVER GOING TO TAKE CARE OF THE FUTURE PATIENTS. ESPECIALLY WHEN YOU HAVE A RARE DISEASE IN WHICH 1 STUDY CAN BE DONE AND MAYBE YOU WILL ONLY HAVE 1 CHANCE TO DO THAT 1 STUDY. SO, THOSE ARE THE WAYS TO LINE OUT THESE OPINIONS AND I'M--I'M PERFECTLY HAPPY TO HAVE OTHER PEOPLE SORT OF DISAGREE AND TO FOR OUR ETHICISTS TO MAKE DECISIONS BASED ON THAT. BUT YOU KNOW THESE ARE STILL TOUGH THINGS TO DEAL WITH. >> THEY'RE VERY TOUGH AND IT'S IMPORTANT TO REMEMBER THAT WE'RE TALKING ABOUT RESEARCH HERE. WE ARE TALKING ABOUT DOING RESEARCH SOMETIMES WITH PEOPLE WHO HAVE ILLNESSES AND WANT TREATMENT. BUT WE'RE ALSO TALKING ABOUT RESEARCH WITH HEALTHY VOLUNTEERS WHO ARE NOT PARTICIPATE NOTHING RESEARCH BECAUSE THEY WANT TREATMENT, AND WE'RE NOT DENYING THEM TREATMENT, WE'RE SUBJECTING THEM TO RISK SO WE CAN LEARN SOMETHING. IT'S A VERY DIFFERENT EQUATION. SO IN THE CONTEXT OF RESEARCH, FOR THAT THE REASONS OF WHY WE THINK RESEARCH IS IMPORTANT TO DO, WE SOMETIMES ASK PEOPLE TO TAKE RISKS THAT THEY OTHERWISE WOULD NOT NEED TO TAKE. AND WE ALSO ASK THEM TO PARTICIPATE IN STUDIES WHERE THEY MAY OR MAY NOT BENEFIT AT ALL. WHETHER THEY HAVE A DISEASE OR NOT. AND I THINK THOSE ARE IMPORTANT DISTINCTIONS FROM TAKING CARE OF PATIENTS IN ANOTHER KIND OF SETTING. PLEASE. >> I HAVE 2 QUESTIONS, I THINK. I'M STILL GRAPPLING WITH IF YOU INVOLVED AT ALL IN THE PROTOCOL DEVELOPMENT AND PARTICIPATING IN THE STUDY, PHYSICALLY. SO I MOSTLY DO HUMANS, HEALTHY VOLUNTEER STUDIES, VACCINE STUDIES, AND WE--WE RECRUITED SOME OF THE PEOPLE WHO WORK IN THE SAME LAB AND THEY DON'T DO ANYTHING SPECIFICALLY TO DO WITH THE PROTOCOL OR ANY CLINICAL SIDE OF IT. THEY MAY END UP SEEING SOME OF THE SAMPLES AND BE ABLE TO DO SOME OF THE LAB EVALUATIONS THAT WE'RE DOING SO WE TELL THEM NOT WHAT THE IDNUMBERS WERE SO WE HAD TO BLACK OUT THE ID NUMBER OR NOT WRITE IT AT ALL SO IN CASE THEY GOT TO SEE THE SAMPLES THEY COULD NOT IDENTIFY WHICH 1 WAS THEIRS AND WHICH 1 WAS. BUT IF YOU I'M TRYING TO PEOPLE OF ALL PEOPLE IN THE CLINICAL TEAM IF 1 OF OF THEM WAS IN THE STUDY HOW WOULD THAT EFFECT THE STUDY? I'M NOT SURE HOW MUCH YOUR INVOLVEMENT WAS IN THE STUDY, IN THE RUNNING OF THE TRIAL ITSELF. >> THAT WAS A QUESTION. IN FAIRNESS IT COULD BE UNFAIR TO NOT ALLOW AN EMPLOYEE TO PARTICIPATE BUT I SEE THE ISSUE RELATED TO DATA COLLECTION AND REPORTING AND FOR INSTANCE I HAVE THE BEST INTEREST OF THE PRODUCT-LIFE BUT I WOULD ETHICALLY DO THAT AS A PERSON AND MY PARTICIPATION IN THE TRIAL, I--I DO REGULARLY HELP REPORT THE DATA THAT COMES OUT OF IT BUT I'M NOT MYSELF COLLECTING COLLECTING DATA OR INPUTTING DATA. BUT WE DO ALLOW NURSES TO COLLECT DATA BUT THEY WON'T HANDLE THEIR OWN DATA. BUT ANOTHER NURSE AND TEAM FEELS THEY HAVE NOTHING TO DO WITH THEIR OWN DATA THAT IT'S--THAT THE RESULTS WHAT YOU DO WITH THE DATA AND HOW YOU REPORT IT AFTERWARDS WON'T BE EFFECT SAID AND I THINK IT'S JUST COMES BACK TO CONSENTING AND AS A PARTICIPANT UNDERSTANDING THAT YOU KNOW YOU DO HAVE TO REPORT ANYTHING AND MAKING SURE THAT THE EMPLOYEES UNDERSTAND THAT THEY HAVE TO ACT AS A PARTICIPANT WHEN THEY'RE PARTICIPATING AND THEY CAN ACT AS AN EMPLOYEE WHEN THEY'RE NOT PARTICIPATING BUT THERE'S A FINE LINE AND IT CAN BE CROSSED BUT I THINK THAT IF YOU--IF YOU ADDRESS THAT IN THE BEGINNING AND IF YOU TALK ABOUT IT AND IF YOU HAVE THE ETHICS CONSULT WHICH DOES GET YOU THINKING ABOUT THESE LITTLER PIECES, THEN I THINK IT CAN BE AVOIDED AND I STILL THINK THAT EMPLOYEE PARTICIPATION CAN AND SHOULD BE ALLOWED AND THAT, YOU KNOW AS A HEALTHY PARTICIPANT, I ENJOY BEING ABLE TO PARTICIPATE. >> THANK YOU. I THINK IT'S ANOTHER GREAT EXAMPLE OF THE TENSION BECAUSE THERE ARE SOME THINGS WE TRY TO DO WHEN EMPLOYEES ARE ENROLLED TO TRY TO PROTECT THE EMPLOYEE AND OTHER THINGS WE DO TO PROTECT THE SCIENCE, MAKE SURE THE SCIENCE IS NOT BIASED IN SOME WAY. AND THOSE ARE BOTH IMPORTANT. IT'S THE SAME TENSION WE'VE BEEN TALKING ABOUT ALL THE WAY THROUGH. SO OUR TIME IS UP. I WANT TO THANK OUR PANELISTS AGAIN FOR A WONDERFUL CONVERSATION. [ APPLAUSE ] AND WE MIND EVERYBODY, 2 THINGS, NEXT WEEK THERE IS NO CLASS BECAUSE IT'S YAM KIPPUR, SO I WILL SEE YOU 2 WEEKS FROM THIS MORNING AND THOSE THAT HAVE THE TIME AND INTEREST, GRAND ROUNDS STARTS AT NOON. THANK YOU.