I WOULD LIKE TO START THE MEETING BY GOING AROUND THE TABLE AND HAVING PEOPLE INTRODUCE THEMSELVES. WE'LL START WITH LINDA. >> GOOD MORNING I'M LINDA COLEMAN THE DIRECTOR OF THE HUMAN RESEARCH PROTECTION PROGRAM AT YALE UNIVERSITY. >> GOOD MORNING I'M SANDY BERRY. THE CHAIR OF THE RAND HUMAN SUBJECTS PROTECTION COMMITTEE. >> GOOD MORNING. MS. ANGAL FROM SOUTH DAKOTA. >> I'M MARY ELLEN ALLEN FROM SAN FRANCISCO. >> STEVEN ROSENFELD, CHAIR. >> JOE MENIKOFF. >> JOANNE LESS IN THE OFFICE OF THE COMMISSIONER AT FDA. >> TOM PAYNE A SENIOR POLICY ANALYST IN THE OFFICE OF SCIENCE POLICY AT NIH >> JANET FREEMAN DAILY. >> NANCY KING, WAKE FOREST SCHOOL OF MEDICINE. >> SKIP JOHNSON, JOHNSON JOHNSON. >> WALTER STRAUS WITH MERCK. >> CONSUELO WILKINS HEALTH EQUITY OF VANDERBILT. >> I'M FROM THE GEORGIA STATE COLLEGE OF LAW. >> THANK YOU. ANY EX-OFFICIOS OR PEOPLE SITTING IN THE AUDIENCE WHO WOULD LIKE TO INTRODUCE THEMSELVES? WE SEE YOU. ALL RIGHT. THANK YOU. AS OUR FIRST ORDER OF BUSINESS I'D ENTERTAIN A MOTION TO APPROVE THE MINUTES FROM OUR LAST MEETING. MOVED. DO WE HAVE A SECOND? MOVED AND SECONDED. DISCUSSION? DOES ANYONE HAVE COMMENTS OR CHANGES TO THE MINUTES? ALL IN FAVOR OF APPROVING LAST MEETING'S MINUTES SAY AYE. OPPOSED? ABSTAINING? MOTION PASSES. THANK YOU. ALL RIGHT. WE'LL MOVE RIGHT INTO THE WELCOME REMARKS. SO I'LL START. THERE'S A COUPLE OF THINGS I WANTED TO FILL THE COMMITTEE IN THAT HAPPENED AT THE SUBCOMMITTEE MEETING. AND YOU SEE THOSE REFLECTED IN THE AGENDA SO THERE WERE TWO ITEMS WE DISCUSSED LAST TIME NOT ON TODAY'S AGENDA AND THOSE WERE SIGHT MONITORING AND THE CONSEQUENCES OF UNCHECKING THE BOX. I WANTED TO FILL YOU IN ON WHY THOSE ARE NOT APPEARING TODAY I THINK FIRST IN TERMS OF UNCHECKING THE BOX AND ITS CONSEQUENCES THE SUBCOMMITTEE FELT THAT EMBODIED TWO SEPARATE ISSUES. ONE WAS SORT OF THE INSTITUTIONAL CONSEQUENCE OF NO LONGER HAVING THIS ENFORCEABLE COMMITMENT AND HOW INSTITUTIONS SHOULD REVIEW RESEARCH PREVIOUSLY THEY REVIEWED UNDER THE COMMON RULE. THE SECOND WAS THE OPPORTUNITY RAISED BY UNCHECKING THE BOX AND HOW WE SHOULD BE REVIEWING ALL THE NEW KINDS OF RESEARCH THAT DON'T SIT WELL WITHIN THE REGULATIONS AND THAT ACTUALLY MAY START WITH INSTITUTIONS. I THINK THAT'S HOW WE GOT TO IT IN THIS TOPIC AND GOES BEYOND THAT BECAUSE WE'RE TALKING ABOUT THINGS LIKE GENOMICS AND BIG DATA THAT HAVE IMPLICATIONS FOR INDUSTRY AND OTHERS. IT FELT BOTH WERE VERY LARGE TOPICS. I'LL GET BACK TO THE INSTITUTIONAL PIECE. THE SUBCOMMITTEE FELT THE ISSUES WEREN'T NARROW ENOUGH FOR ADDRESS YET AND IT WOULD BENEFIT BOTH PIECES FROM HAVING COMMUNITY INPUT IN THE FORM OF A PANEL. SO WE'RE GOING TO TALK ABOUT DOING THAT FOR THE MARCH MEETING FORTUITOUSLY. IT'S THE ONLY TIME I'LL USE THAT ADJECTIVE IN RELATION TO A VIRTUAL MEETING. IT'S EASIER TO INCLUDE THAT NA VIRTUAL MEETING TO INCLUDE PEOPLE. MORE ON THAT TO COME BUT WE WON'T DISCUSS THAT AT THIS MEETING. AS FAR AS SIGHT MONITORING I THINK IT'S FAIR TO SAY THE COMMUNICATE FELT IT WAS A CONCERN BUT A COMPONENT OF SOMETHING BIGGER. THE INSTITUTIONAL RESPONSE TO THE SINGLE IRB MANDATE AND THE CONSEQUENCES OF THAT FOR THE HRPP PROGRAMS. AND THERE WAS LIVELY DEBATE ON THE CALL BECAUSE THERE'S A QUESTION WHETHER IT'S AN INSTITUTIONAL ISSUE AND CHANGE HARD AND CHANGE CAN BE EXPENSIVE OR WHETHER IT MIGHT IMPACT PARTICIPANTS WHICH WOULD MAKE IT AN IRB AND ETHICAL ISSUE WE MAY HAVE CONCERN OVER. AND AGAIN SITE MONITORING IS A SMALL PIECE OF THAT. AGAIN THE SUBCOMMITTEE FELT IT WAS SOMETHING SACHRP WHERE WE SHOULD HAVE MORE VOICES AND FOR US TO OPEINE WITHOUT THE GROUP IS SOMETHING WE SHOULD HAVE. I'M NOT AS CONVINCED WE KNOW WHAT WE'RE ASKING THERE SO YOU'LL PROBABLY SEE IT DEVELOP OVER TIME IF WE DECIDE TO DO IT. THEN THE LAST THING I WANT TO VISIT BECAUSE I CONTINUE TO BE ASKED ABOUT IS OUTSIDE THIS CONTEXT IS THE ISSUE THAT WAS RAISED IN THE KOGER ABOUT WHAT HAPPENS AT A COMPLIANCE DATE FOR STUDIES IN THE NEW IRB TRANSITIONED TO THE UPDATING COMMON RULE BEFORE THAT. THEISH SUE IF YOU -- THE ISSUE IS IF YOU WERE APPROVED YESTERDAY OR FIVE YEARS AGO AND TRANSITIONED, COME JANUARY, THE REGULATIONS SAY YOU HAVE TO BE REVIEWED BY A SINGLE IRB. THAT'S A DEFINED NUMBER OF STUD STUDIES SO IT WILL EVENTUALLY GO AWAY BUT IN THE COMMUNITY SEEMS LIKE A BURDEN THAT DIDN'T SERVE A PURPOSE. WE TALKED ABOUT RAISING THAT HERE. WE KNOW THE OHRP AND THE DEPARTMENT ARE WORKING ON THAT AND SOMETHING IS FORTHCOMING AND NAT APPROPRIATE FOR US TO GET INVOLVED. SO THAT IS ALSO NOT SOMETHING WE'LL BE DISCUSSING. THOSE ARE MY NOTES FOR THE DAY. JERRY. AND ALSO, WELCOME. >> THANK YOU, STEVEN. PRIMARILY I'D LIKE TO WELCOME EVERYBODY AND THANK EVERYBODY FOR ALL THE WORK BEHIND THE SCENES THAT BUILDS UP TO THIS MEETING. PARTICULARLY TO THE SUBCOMMITTEE MEMBERS AND SUBCOMMITTEE CHAIRS AND THE COMMITTEE MEMBERS WHO WORKED TOGETHER WITH THE SUBCOMMITTEES,EX-OFFICIOS AND THE STAFF, JULIA AND SAYS -- CECILIA AND EVERYBODY HERE IN THE ROOM OR ON THE INTERNET, THE PUBLIC, EVERYBODY. THANK YOU ALL. WE LOOK FORWARD TO AN INTERESTING MEETING. LET ME ADDRESS THE ISSUE STEPHEN BROUGHT UP. WE'RE NOT TRYING TO HIDE ANYTHING. IN TERMS OF THE GAP YEAR AND SINGLE IRB REQUIREMENT, CERTAINLY FOR MANY OF US IT WAS NOT OUR INTENT THAT YES, YOU WOULD BE FORCED TO GO FROM AN ONGOING STUDY WITHOUT A SINGLE IRB AND AS OF THE APPROPRIATE DATE NEXT JANUARY YOU'D HAVE TO SHIFT TO HAVE A SINGLE IRB. WE WERE SYMPATHETIC TO THE ISSUES RAID IN THE KRO -- RAISED IN THE KROGER JOINT LETTER. WE HAVE BEEN WORKING ON A FIX FOR QUITE A WHILE. UNFORTUNATELY WELL ALL THE THINGS IN THE FEDERAL GOVERNMENT YOU OFTEN END UP ENCOUNTERS HURDLES TO GET SOMETHING OUT THE DOOR. HOPEFULLY IT WON'T BE TOO LONG BEFORE SOMETHING GETS OUT THE DOOR. WE SAY THIS MANY TIMES AND THEN IT TAKES LONGER THAN YOU THINK BUT WE'RE WORKING ON IT AND IT'S NOT LIKE WE EVER WANTED TO FORCE PEOPLE TO SHIFT MID STREAM IN TERM OF THAT. THAT'S WHERE IT IS IN TERMS OF THAT ISSUE. AGAIN, THANKS EVERYBODY FOR AND I JUST WANT TO NOTE ONE THINGS IN THE NEWS IT'S SOMETIMES INTERESTING THE WAY ISSUES REGARDING HUMAN SUBJECTS SHOW UP IN UNEXPECTED AREAS DEPENDING ON WHAT AREAS YOU WORK IN AND GIVEN WE'RE TWO WAYS ANNOUNCEMENTS FROM THE NOBEL LAUREATES IN ECONOMICS. NOT EVERYBODY'S AWARE THERE'S ANALOGS OF CLINICAL TRIALS AND OTHER AREAS OF RESEARCH EFFECTIVELY RANDOMIZED TRIALS, INVENTIONAL MAN DOMIZED TRIALS THAT AREN'T ALWAYS ABOUT THAT AND THE NOBEL LAUREATES ARE KNOWN FOR AND ONE OF THE REASONS THEY GOT THE NOBEL IS THEY ACTUALLY STARTED IN THE FIELD OF ECONOMICS DOING THINGS THAT ARE EFFECTIVELY ANALOGS OF CLINICAL TRIALS BUT LOOKING AT HUPAN BEHAVIOR AND ASSIGNING PEOPLE TO DIFFERENT ECONOMICS OF CHANGES. OFFERING A VACCINE FOR FREE RATHER THAN CHARGING SOMEBODY A DOLLAR OR TWO DOLLARS. IT'S A FASCINATING FIELD AND RELEVANT TO HOW WE DEAL WITH PROTECTIONS FOR HUMAN SUBJECTS. IT'S WORTH TAKING A LOOK AT. THERE'S A REALLY GOOD BOOK CALLED POOR ECONOMICS WHICH IS DESIGNED FOR A PUBLIC AUDIENCE AND WORTH TAKING A LOOK AT IF YOU'RE INTERESTED IN THAT. I'LL LEAVE IT AT THAT. BACK TO STEPHEN. >> THANK YOU. I WAS REMISS IN NOT EXPLICITLY THANKING THE OHRP STAFF. THERE'S A LOT THAT GOES INTO PLANNING A MEETING AND THE TIMING WASN'T GREAT FOR THEM AND AN APPRECIATE HERE WE ARE AND EVERYTHING LOOKS LOVELY SO THANK YOU. WITH THAT WE'RE BACK ON SCHEDULE AND WE'LL TURN TO RE-CONSENT. >> THERE'S A SLIGHT CHANGE IN THE AGENDA. I'M MARK BARNES UNDERSTUDY AND START WITH END USER LICENSE AGREEMENTS AND MARK WILL BE LIKE BIG BROTHER ON THE PHONE. WE'LL HEAR HIS VOICE HOPEFULLY. >> HI, DAVID. >> WE'RE GOING TO WORK OFF THE VERSION TO LOOK AT ALL THE EDITS IN PLACE SINCE THE LAST TIME THIS WAS VIEWED. I'LL GIVE FOLKS A SECOND TO SWITCH GEARS AND GET TO THAT DOCUMENT AND WE'LL DO RE-CONSENT AT 11:00. >> WOULD YOU LIKE TO GUIDE THE DISCUSSION? >> CAN YOU HEAR IS THE --? >> THE VERSION YOU HAVE AND DAVID POINTED YOU TO SHOWS CHANGES FROM THE LAST VERSION THAT WE DISCUSSED AT SACHRP A FEW MONTHS AGO. IN IT ALSO THERE ARE EMBEDDED SOME NOTES IN CAPS I HAD MADE THAT WAS NOT IN THE ORIGINAL DOCUMENT. THESE ARE NOTES I MADE FOR DAVID FOR FORRESTER AND THE OTHER SUBCOMMITTEE MEMBERS IN REGARD TO WHAT THE COMMENTS WERE MADE ON THE DOCUMENT LAST TIME. THERE WERE SOME CLARIFICATION POINTS YOU ALL HAD ASKED US TO MAKE IN THE DOCUMENT AND I THINK THOSE HAVE BEEN MADE. THE MAIN INSTRUCTION WAS THAT YOU WANTED A FOURTH SCENARIO CREATED TO TEASE OUT SOME COMPLEXITIES OF ONE OF THE THREE SCENARIOS THAT HAD BEEN PRESENTED IN THE ORIGINAL DOCUMENT. THAT'S WHAT WE HAVE DONE. ALSO YOU ASKED WE HAVE RECOMMENDATIONS FOR EACH OF THE SCENARIOS SO THOSE THINGS HAVE BEEN DONE HERE. SO WHAT I THINK IT MIGHT DO AND I'LL PAUSE IN CASE THERE'S GENERAL COMMENTS FROM ANY OF YOU BUT I'LL GO ON TO THE SPECIFIC CHANGES RECOMMENDED IN THE DOCUMENT. BUT LET ME PAUSE AND SEE IF DAVID YOU WANT TO ADD ANYTHING OR ANYONE ELSE WANTS TO SAY SOMETHING? >> THAT'S A GOOD INTRODUCTION FROM MY END. I DON'T KNOW IF THE SACHRP MEMBERS HAVE QUESTION OR COMMENTS. OKAY, GO AHEAD, MARK. >> UNLESS PEOPLE HAVE A SPECIFIC COMMENT I'LL SKIP OVER THE MINOR EDITORIAL CHANGES AND LET ME GO TO LINE 110. THIS IS NOT SIGNIFICANTLY CHANGED BUT THERE IS A COMMENT FROM DAVID FORRESTER WITH WHICH I AGREE BUT WE'RE HAPPY TO DO WITH THE TEX WHATEVER -- TEXT WHATEVER YOU ALL WANT US TO DO. THIS IS A LITTLE BIT OF A FROLIC AND DETOUR FROM THE MAIN POINT OF THE DOCUMENT. IT'S A SURVIVAL FROM AN EARLIER VERSION AND DAVID'S RECOMMENDATION IS WE DELETE THE HIGHLIGHTED LANGUAGE HERE. THE POINT THAT WAS TRYING TO BE MADE WAS IN REGARD TO THE FUNCTION OF IRBs AS LOOKING AT AND APPROVING POTENTIALLY DOCUMENT ARE ACTUALLY NOT CONSTRUCTED OR CREATED PURSUANT TO A COMMON RULE REQUIREMENT BUT PURSUANT TO THE REQUIREMENT OF AN ANCILLARY REGULATORY REGIME. IN THIS CASE, THE POINT WAS WITH THE ADVENT OF HIPAA AND 20 YEARS AGO NOW THERE WAS AN ACTIVE DEBATE AMONG IRBs AS TO WHETHER THE IRBs SHOULD REVIEW THE HIPAA AUTHORIZATION THAT WERE NECESSARY AS A LEGAL MATTER TO PROTECTING HEALTH INFORMATION AND USING THAT IN THE COURSE OF THEIR RESEARCH. THEY'RE USING IT TO DISCLOSE THE INFORMATION. SOME IRBs DECIDED THEY WOULD INDEED REVIEW THE HIPAA ORGANIZATION. OTHERS DECIDED THEY WOULD NOT. THE POINT IS DIFFERENT IRBs TOOK THE TEXT WE RECOMMEND DELETED AND DIFFERENT POSITIONS. IT'S A HISTORICAL POINT. IT'S NOT NECESSARY FOR THE FLOW OF THE DOCUMENT AND DAVID FORRESTER AND I RECOMMEND IT BE REMOVED BECAUSE WE'RE NOT SURE IT ADDS ANYTHING TO THE DOCUMENT. AND WE'LL PAUSE IF ANYONE HAS A DIFFERENT IDEA. I DOESN'T HARM THE DOCUMENT BUT IT SEEMS TO AT THIS POINT IN THE DOCUMENT COME OUT OF NOWHERE. >> I SEE A LOT OF PEOPLE NODDING IN AGREEMENT WITH YOUR ASSESSMENT, MARK. >> OKAY. >> WE CAN ELIMINATE THAT. >> WE DELETED IT. >> LET'S GO ON TO THE PARAGRAPH THAT BEGINS ON LINE 120. WE'RE TRYING TO NOTE THAT THERE ARE MANY LEGAL DOCUMENTS AND LEGAL RELATIONSHIP UNDERLIE AND UNDERPIN RELATIONSHIPS BUT PRECEDE THE RESEARCH RELATIONSHIPS AND NOT ROUTINELY EXAMINED AND WHEN A BEHAVIOR STUDY IS CONDUCTED AT A BASEBALL GAME THE IRB WOULD NOT EXAMINE THE TICKET CONTRACT ON FOUL BALLS. IT SEEMS SILLY BUT IT'S A PUBLIC CONTRACT AND A TYPICAL CONTRACT IN WHICH INDIVIDUALS WHO ULTIMATELY BECOME SUBJECTS MAY ENTER. IF YOU GO TO THE BOTTOM HERE IN TERMS OF SERVICE IT'S BASED ON THE NATURE OF THE CONTRACT AS BEING BETWEEN THE SUBJECT AND THE EXTERNAL ENTITY AS IS THERE NO DISINTERMEDIATING ENTITY. THE THE LANGUAGE SUGGESTED FOR VERIFICATION THE CONTRACT STILL BETWEEN THE MANUFACTURER OF THE APP THAT IS OF THE DEVICE OR SOFTWARE AND THE SUBJECT. IF THE SUBJECT DOESN'T LIKE THE TERM OF THE APP, ULTIMATELY THE SUBJECT CAN REFUSE TO AGREE TO THE PP AND NOT PARTICIPATE IN THE RESEARCH. DAVID IS MAKING CLEAR HERE ULTIMATELY WHEN THESE ARE THESE KINDS OF PUBLIC OR TYPICAL CONTRACTS OUTSIDE THE RESEARCH RELATIONSHIP, THAT REALLY AS A MATTER AS A GENERAL MATTER IS THE PROVINCE OF THE INDIVIDUAL AND THE THIRD PARTY. IT'S NOT THE PROVINCE OF THE IRB TO SECOND GUESS IT AND ULTIMATELY THE INDIVIDUAL DOES HAVE THE OPTION NOT TO ENTER INTO THAT CONTRACT. THIS IS NOT CHANGING THE MEETING OF ANYTHING. I THINK IT'S A CLARIFICATION DAVID FORRESTER HAD SUGGESTED. LINE 177 THE PARAGRAPH THERE IS MEANT TO IDENTIFY A SCENARIO THAT REALLY WAS BURIED AND PREVIOUSLY THE THIRD -- SORRY, BURIED IN THE THIRD SCENARIO. REMEMBER THE SCENARIOS ARE BASICALLY THE FOLLOWING. THE SCENARIOS REPRESENT A CONTINUUM OF INVOLVEMENT OF THE RESEARCHER AND MANUFACTURER OF THE APP WITH THE APP ITSELF AND THE INTEGRATION OF THE APP AND THE RESEARCH WITH THE FIRST SCENARIO BEING THE LEAST INVOLVEMENT THERE AND THE FOURTH SCENARIO BEING THE MOST SERIOUS DEGREE OF INVOLVEMENT OF ALL THE DIFFERENT PARTIES. THE FIRST SCENARIO REMEMBER IS THAT WHEN A POTENTIAL SUBJECT, THIS IS ON LINE 156 OBTAINED A PUBLICLY AVAILABLE APP ON HIS OR HER OWN INITIATIVE PRIOR TO THE PERSON'S INVOLVEMENT WITH THE RESEARCH AND THE ORIGINAL USE OF THE APP IS QUITE SIMILAR TO OR EVEN THE SAME AS THE USE OF THAT APP FOR PURPOSES OF THE STUDY. THIS IS AN INDIVIDUAL. IN THIS CASE, WE HAVE THOUGHT ABOUT THIS AND THE SUBCOMMITTEE AS PIGGY BACKING THE APP ON A CONSUMER LATER RECRUITED AS A RESEARCH SUBJECT BECAUSE HE OR SHE ALREADY AGREED TO USE THE APP AND LIKELY DOING IT IN THEIR DAILY LIVES. IN THIS CASE THE SUBJECT HAS ALREADY AGREED TO THE TERMS OF SERVICE AND END USER LICENSE AGREEMENT INDEPENDENTLY OF THE STUDY AND PRECEDING THE STUDY AND THE STUDY IS ASSUMING THE INDIVIDUAL AND COMES IN LATER AND ASSUMES THE INDIVIDUAL HAS BEEN COMFORTABLE WITH THE TERMS OF USE OF THE APP. SO WE TEASED OUT A SECOND SCENARIO WHEN A SUBJECT HAS OBTAINED A PUBLICLY AVAILABLE APP ON HIS OR HER INITIATIVE PRIOR TO THE INVOLVEMENT WITH THE RESEARCH BUT THE ORIGINAL USE OF THE APP IS SOMEWHAT DIFFERENT THAN THE USE OF THE APP IN THE STUDY. IN OTHER WORDS, THE STUDY WOULD BE INTERVENING TO ENCOURAGE OR REQUIRE THE INDIVIDUAL TO USE AN APP BUT IN A WAY THAT WAS NOT CONTEMPLATED WHEN THE INDIVIDUAL ORIGINALLY OBTAINED THE APP. THE PERSON MAY HAVE A FITBIT FOR PURPOSES OF TRYING TO TRACK HIR ACTIVITY BUT THE STUDY MAY COME IN TO SEE IF THE FITBIT CAN BE USED TO DIAGNOSE SLEEP APNEA BUT WOULD BE A NEW USE OF THE APP. MANUFACTURER OF THE APP IS NOT REALLY INVOLVED IN THE RESEARCH OR CAUSE THE RESEARCH. THE POINT THE POINT MAYBE CONCERNED WITH THE SECOND SCENARIO WITH THE TERMS OF VERSUS THE TERMS OF PARTICIPATION IN THE RESEARCH IN THE PROTOCOL AND CONSENT. THIS DOESN'T CHANGE THE MEANING BUT TEASING OUT THE CONTINUUM BETWEEN THE FIRST AND THIRD SCENARIO. LET ME PAUSE THERE TO SEE IF THERE'S COMMENTS. >> WE DISCUSSED THAT BUT IT WAS EMBEDDED IN THE SECOND SCENARIO. >> THAT'S RIGHT. >> FOR REVIEW, IF YOU LOOK AT LINE 184 THE THIRD SCENARIO WHICH BECOMES MORE COMPLEX IN REGARD TO THE RELATIONSHIP OF ALL THE PARTIES AND THE RELATIONSHIP OF THE APP TO THE STUDY DESIGN AND WHEN THE RESEARCH DESIGN REQUIRES THE USE OF THE APP AND THE RESEARCH ENROLLMENT REQUIRED THE ACQUISITION OF THE APP. IT'S AN APP THE SUBJECT DID NOT HAVE BEFORE OR CHOOSE ON HIS OR HER OWN BUT THE STUDY PROTOCOL ELIGIBILITY CRITERIA SAID IF YOU WANT TO PARTICIPATE IN THE STUDY ONE CRITERIA IS YOU MUST ACQUIRE THE APP BECAUSE THE APP IS NECESSARY FOR THE STUDY. SO IN THIS CASE THE RESEARCH TEAM HAS INSTIGATED THE STUDY SUBJECT'S ACQUISITION OF THE APP AND INS TI -- INSTIGATED THE ULA OR TERMS OF SERVICE. THIS IS CROSSING INTO A TERRITORY WHERE THE RESEARCH REQUIRES THE USE OF THE APP THAT WAS NOT PREVIOUSLY CON TOMB -- CONTEMPLATED OR REQUIRED BY THE SUBJECT. THE FOURTH SCENARIO WHICH IS THE MOST COMPLEX AND PROBABLY MOST CONCERNING WHEN THE APP MANUFACTURER IS INVOLVED IN THE STUDY AND THE DATA IS INTENDED TO PROMOTE THE DESIGNER OF THE STUDY. IN THIS CASE THERE'S MORE INVOLVEMENT. THE STUDY HAS BEEN DONE IN THIS SCENARIO IN SOME WAYS IT MAY BE DONE FOR ACADEMIC KNOWLEDGE BUT IT'S ALSO BEING DONE FOR POTENTIAL BENEFIT OF THE MANUFACTURER OF THE APP. THAT WOULD INDICATE A HIGHER DEGREE OF CONCERN THE RESEARCHER AND IRB SHOULD HAVE FOR THE TERMS OF SERVICE. AT THE SAME TIME THE MANUFACTURER IS DEEPLY INVOLVED. IT'S THE COMMERCIAL ENTITY THAT WRITES THE TERMS OF SERVICE AND THE APP MANUFACTURER IS MOST SUSCEPTIBLE TO PRESSURE FROM THE REQUEST OR STIPULATION OF THE IRB ABOUT THE POTENTIAL CONFLICT WITH THE TERMS OF SERVICE WITH THE CONSIDERATIONS OF THE COMMON RULE AND THE INFORMED CONSENT ITSELF. IN THIS CASE THOUGH THE MANUFACTURER MAY BENEFIT IT'S PRONE TO STIPULATION IT MAY CHANGE OR ALTER THE TERMS AND CONDITIONS SO THEY DO NOT CONFLICT WITH EITHER THE COMMON RULE OR WITH THE PROTOCOL AND THE IC. NOTHING IS CHANGED IN THAT REGARD BUT I WANTED TO BE CLEAR AND REMIND PEOPLE OF THE CONTINUUM WE'RE TALKING ABOUT. AGAIN, LET ME PAUSE THERE. >> WE'RE MARK. >> OKAY. IN THE NEXT SECTION WE GO TO ACTUAL RECOMMENDATIONS WHAT TO DO WITH THE FOUR SCENARIOS AND THE RECOMMENDATIONS ARE CALIBRATED TO THE DEGREE OF CONCERN THAT AS A REGULATORY AND ETHICAL MATTER WE THINK THE SUBCOMMITTEE THINKS THE RESEARCHER AND IRB OUGHT TO BE CONCERNED. SO IN THE FIRST SCENARIO REMEMBER IS THE LEAST INVOLVEMENT THE SUBJECT ALREADY GOT THE APP. APP MANUFACTURER'S NOT INVOLVED IN THE RESEARCH. OUR RECOMMENDATION FOR SACHRP HERE IS THE RISKS INVOLVED WITH THE USE OF THE APP ARE NOT RESEARCH RISKS AND THERE IS EXCULPATORY LANGUAGE THAT RISKS THE APP MANUFACTURER THAT INVOLVED THE USE OF THE APP AND NOT THE RESEARCH. IN OUR VIEW OUR RECOMMENDATION IS THAT THE EULA TERMS OF SERVICE DOES NOT TYPICALLY NEED TO BE REVIEWED BY THE IRB AS PART OF ITS REVIEW OF THE RESEARCH. MAYBE I'LL GO THROUGH THE RECOMMENDATIONS AND THEN WE CAN TALK. >> THIS IS CONSUELO WILKINS. MY QUESTION IS ABOUT IF THE RESEARCHER ASKED THE MANUFACTURER TO CHANGE THE APP IN SOME WAY. THAT WOULD BE FOR THE STUDY. WOULD YOU SAY THE MANUFACTURER IS THEN INVOLVED IN THE STUDY IN SOME WAY OR IS THAT SEEN AS A SCENARIO THREE OR FOUR? THE RESEARCHER, FOR EXAMPLE, ASKED THE FITBIT FOLKS TO ADD IN SOME DATA COLLECTION THAT WASN'T ALREADY BEING DONE WITH THE FITBIT APP SO WHEN THIS PERSON IS IN A COMMUNITY OR AREA WHERE THERE'S NO GROCERY STORES AND PING A MARKET IN SOME WAY. ARE THEY THEN INVOLVED OR THE CONDUCT OF THE STUDY? >> CONSUELO, I WOULD SAY IN ALL LIKELIHOOD THAT COULD HAPPEN IN ANY OF THE FOUR SCENARIOS BUT IF IT HAPPENED AND THE MANUFACTURER RESPONDED IN A POSITIVE WAY, THE MANUFACTURER IS PROBABLY DOING THAT NOT OUT OF THE GOODNESS OF ITS HEART BUT RATHER BECAUSE IT THINK IT HAS SOMETHING ULTIMATELY TO BE GAINED FOR THE MANUFACTURER BY ALTERING AN OTHERWISE UNBURIED EULA OR TERMS OF SERVICE. I THINK AS A PRACTICAL MATTER THOUGH THE SCENARIO YOU PROPOSED COULD ARISE IN ANY OF THESE THINGS BECAUSE A RESEARCHER CAN ALWAYS ASK THE MAP MANUFACTURER TO ASK SOMETHING I THINK 99 TIMES OUT OF 100 THAT WOULD ARISE ONLY IN SCENARIO FOUR. THAT'S MY OPINION AND A PRACTICAL OPINION. I COULD BE WRONG BUT I THINK THAT'S THE WAY I SEE IT IN REAL LIFE WORKING OUT. >> THIS IS JANET. I THINK IT MATTERS WHETHER THE CHANGE REQUESTS GETS PUSHED TO OTHER USERS AND BECOMES A STANDARD APP TIRE END UP CREATING SOMETHING UNIQUE FOR THE STUDY. THEN IT'S NO LONGER A STANDARD APP. >> RIGHT. IF THAT HAPPENS IF THERE'S A SPECIALTY OR ALTERED APP CREATED NOR PURPOSE OF THE ONE STUDY, THE REASON THE RESEARCHER WOULD HAVE REQUESTED THAT IS SPECIFIC BY -- SPECIFICALLY BECAUSE IN LIKELIHOOD IT WANTS IT CONSISTENT WITH THE STUDY AND TO SUPPORT THE PROTOCOL AND ULTIMATELY THE RESEARCHER IN THAT CASE OUGHT TO ONLY REQUEST SOME CHANGE THAT WOULD AT LEAST NOT BE INCONSISTENT WITH THE CONSENT FORM AND PROTOCOL. IN MOST CASES IT WOULD BE IN ALMOST ALLCATIONS -- ALL CASES TO THE SUBJECT OF THE -- BENEFIT OF THE SUBJECT. I THINK WE COULD ADD A SENTENCE OR TWO TO THE DOCUMENT THAT CUTS ACROSS ALL THE SCENARIOS AND SAY TO THE EXTENT THE INVESTIGATOR THINK AN EXISTING APP NEEDS TO BE ALTERED TO FIT A SPECIFIC STUDY AND ONLY FOR A STUDY. OBVIOUSLY THE RESEARCHER SHOULD DO THAT ONLY TO BE CONSISTENT WITH THE PROTOCOL AND PROMOTE THE INTEREST OF SUBJECTS. >> SKIP. >> SO MARK, THESE QUESTIONS I WAS THINK ABOUT IN THE USE OF THE SECOND SCENARIO WHEN YOU SAY THE APP IS DIFFERENT FROM THE STUDY USE. THE QUESTIONS ABOUT MODIFICATION AND DATA SUGGEST AND YOUR ANSWER SUGGESTS IF THE A -- IF THE APP NEEDS TO BE MODIFIED TO COLLECT DATA BUT SOMEHOW THE DATA ARE NOT BE USED EXCEPT NOW BEING USED IN A RESEARCH CONTEXT OPPOSED TO WHATEVER ELSE MAY THEY BE USED FOR. I THINK THAT COULD MERIT SOME CLARIFICATION. I THINK IF THERE'S A RESEARCH-BASED MODIFICATION, THAT LIKELY UNDER TWO THE ONLY WAY YOU COULD INTERPRET THAT IS TO SAY IT DOESN'T REQUIRE SUCH A MODIFICATION AND IN FACT IT WOULD IMPLY THE DATA IS BEING COLLECTED BY THAT APP AND PREVIOUSLY NOT USED IN SOME WAY. THERE COULD BE SOME SEPARATION OF THAT IF THAT'S WHAT YOU'RE SAYING. THERE'S A LITTLE BIT OF LACK OF CLARITY. WHEN I READ TWO ARE THE DATA BEING COLLECTED BUT NOT USED AND WHY IS IT NOT BE COLLECT ORDER USED, ETCETERA. THAT'S MY SUGGESTION. >> MARK, IT SEEMS LIKE WE SHOULD EXPAND THE FOURTH SCENARIO TO ENCOMPASS CHANGES TO THE APP AS WELL AS DESIGN AND DEVELOPMENT OF THE APP. IF YOU HAVE TO GO BACK TO THE MANUFACTURER AND CHANGE THEIR CODE AND CHANGE HOW AS THE PROCESSED DIFFERENTLY, THAT SEEMED TO ME IT WOULD FIT MORE IN SCENARIO FOUR AND TWO IS USE THE FITBIT AND COLLECTING THE SAME DATA BUT NOW YOU'RE TRYING TO DIAGNOSE PAR SIN SONS DISEASE AND ANALYZING IT DIFFERENTLY WITH DIFFERENT APPLICATIONS. >> I AGREE BUT IN NUMBER TWO I MAKE A CLARIFICATION THAT DIFFERENCE IN THE USE OF THE DATA DOESN'T IMPLY A MODIFICATION OF THE APP TO ALLOW THE COLLECTION OF DIFFERENT DATA. I THINK IF WE MADE THE ORIGINAL USE AND DATA COLLECTED THE ORIGINAL USE OF THE APP IS DIFFERENT FROM THE STUDY USE BUT THERE'S NO CHANGE IN THE DATA COLLECT ORDER SOMETHING LIKE THAT. >> OKAY. >> DAVID I'M RUNNING NOTES BUT WOULD YOU ADD NOTES AS WELL. >> WE CAN DO WHAT YOU SAY WITH REGARD TO THE FOURTH SCENARIO PUT INNING SENTENCES THAT ADDRESS CONSUELO'S POINT. >> MARK, WE HAVE ONE MORE QUESTION. I WAS WAITING FOR DAVID TO FINISH WRITING. >> OKAY. >> OKAY. >> THIS IS MARY ELLEN ALLEN. THROUGHOUT THE DOCUMENT THERE'S THE USE OF THE TERM SUBJECTS ACQUISITION OF THE APP. SPECIFICALLY WOULD BE IN SCENARIO THREE AND FOUR. ZIT MAKE A DIFFERENCE -- DOES IT MAKE A DIFFERENCE WHETHER THE SUBJECT IS REQUIRED TO ACQUIRE THE APP ON HIS OR HER OWN OR WHETHER IT'S PROVIDED BY THE SPONSOR AS PART OF THE STUDY? I THINK IT DOESN'T MATTER IF THE EULA AND TERMS OF SERVICE ARE BETWEEN THE SUBJECT AND THE MANUFACTURER. BUT JUST A CLARIFYING QUESTION IF THAT MAKES A DIFFERENCE HOW THE SUBJECT ACQUIRES THE APP. >> I DON'T THINK IT DOES, MARY ELLEN. I THINK THE WAY MOST WORK IS THE APP IS AVAILABLE AND GOES ON TO THEIR OWN IN SOME CASES A SPECIFIC DEVICE PROVIDED LIKE A FITBIT A PERSON DIDN'T ALREADY HAVE BUT IN MOST CASES THEY ARE APPS THAT ARE DOWNLOADED BY THE SUBJECT ON TO THEIR OWN PDA AND AT THE DIRECTION OF THE STUDY TEAM. I THINK IT DOESN'T REALLY MATTER EN TERMS OF THE LEGAL RELATIONSHIP OF THE SUBJECT AND THE MANUFACTURER. >> OKAY. MY SECOND QUESTION IS HOW MUCH IF ANY INFORMATION SHOULD BE REGARDING THE EULA AND TERMS OF SERVICE BEING INCLUDED IN THE PROTOCOL? >> THAT'S A GOOD POINT, MARY ELLEN BECAUSE MOST THE DOCUMENT IS FOCUSSED ON THE INFORMED CONSENT. MAYBE WE SHOULD CLARIFY THAT BUT IT'S NOT REALLY POSSIBLE FOR THE INVESTIGATOR SIMPLY TO PUT THE INFORMATION INTO THE INFORMED CONSENT. THE INFORMATION IN AN INFORMED CONSENT IS A DIRECT OUTGROWTH OF THE STATEMENT AND THE ANALYSIS THAT'S DONE IN THE CONTEXT OF THE PROTOCOL. IT'S NOT JUST A QUESTION OF WHAT'S IN THE INFORMED CONSENT IT'S ALSO A QUESTION IN THIS CASE AND IT OUGHT TO BE REFLECTING THE CONCLUSIONS OF THE PROTE KOL. I THINK IT'S A GOOD POINT. THIS KIND OF THING DOES NOT CONTEMPLATED IN A PROTOCOL AND NEEDS TO BE REFLECTED IN THE INFORMED CONSENT. >> JAENT. -- >> JANET. >> I SEEM TO REMEMBER WE DISCUSSED THIS A LOT LAST TIME BUT IF THE PERSON ALREADY HAS THE APP OR HAS A STANDARD PROCEDURES APP, A SIMPLE LINE IN THE PROTOCOL SAYING WE ASSUME YOU HAVE READ AND ARE WILLING TO ACCEPT THE TERMS OF SERVICE AND THAT'S THE END OF IT. >> IN THE CONSENT OR PROTOCOL? >> I WOULD SAY IT WOULD BE IN THE CONSENT. BUT CONSENTS VOLLEYBALL TO APPROVED -- HAVE TO BE APPROVED AS PART OF THE IRB ANN WAY, RIGHT? -- ANYWAY, RIGHT? >> I'D TAKE A DIFFERENT TACT AS SHE SUGGESTED SAYING IT'S ONLY IN SCENARIO THREE WHERE THE IRB HAS TO DO THE WORK OF INFORMATION IT BUT I DO THINK ONE, WE KNOW NOBODY READS THESE THINGS BUT THERE'S THE DISCONNECT POTENTIALLY BETWEEN THE CONFIDENTIALITY PROTECTIONS OR LACK THEREOF THERE ARE IN THE EULA VERSUS THE PROTECTIONS AN PROMISES MADE IN THE CONSENT FORM FROM THE RESEARCH SIDE OF THINGS. SO IN LOOKING AT IT, MY CONCERN WAS IN ONE OR TWO INSTEAD OF SAYING THEY DON'T HAVE TO DO ANYTHING, I THINK THERE AT LEAST NEEDS TO BE SOME NOTICE IF NOT WE KNOW YOU READ THIS BUT RATHER YOU MIGHT WANT TO BECAUSE THERE MAY BE DIFFERENT OBLIGATIONS ON THE PART OF THE MANUFACTURER THAN WE'RE TALKING ABOUT HERE IN THE RESEARCH. IT'S A LITTLE BIT DIFFERENT THAN THE CONDITION PREDICATE. >> MY READING WAS FOR ONE. I'LL STAY WAY -- AWAY FROM TWO FOR THE TIME BEING BECAUSE IT BLURS THE LINES. THE IDEA IS YOU WERE USING THIS THIS WAY ANYWAY AND WHILE IT'S PROBABLY ABSOLUTELY TRUE YOU DIDN'T READ THE EULA TERMS OF SERVICE AND I READ IT AS THE EULA TERMS OF SERVICE IMPACT THE RISK PROFILE. I THINK IT'S A STRONG CASE THAT IN CASE ONE WHERE YOU'RE USING IT THE SAME WAY IT'S A STRETCH TO CONSIDER THE RISKS OF THE RESEARCH. THAT'S THE ARGUMENT THAT WOULD ARGUE AGAINST BEING OVERLY BURDENSOME AS FAR AS WHAT PEOPLE SHOULD HAVE DO. IF THEY WERE COMFORTABLE WITH IT BEFORE AND BEING USED THE SAME WAY IT'S PART OF THEIR DAILY LIFE THEN WHY ARE YOU RAISING THIS IN THE CONTEXT OF RESEARCH. >> MY RESPONSE IS NOT SO TO SAY IT'S PART OF THE RESEARCH RISK BUT WHILE WE'RE MAKING PROMISES WE'RE GOING TO TAKE YOUR DATA AS CONFIDENTIAL AS POSSIBLE YOU SHOULD BE AWARE SEPARATELY YOUR FITBIT MAY BE USING IT DIFFERENTLY. THERE MAY NEED TO BE AN ALERT AND IT'S NOT THAT IT'S PART OF WHAT WE'RE DOING BUT AS WE'RE MAKING THE PROMISES WHAT YOUR EXPECTATIONS ARE. >> SO I THINK THAT'S GOING TO BE A POINT OF DISCUSSION. I THINK THAT'S A GRAY AREA WE'LL HAVE TO COME TO CONSENSUS ON. I DON'T KNOW NANCY OR JANET. WHO WAS UP FIRST? NANCY. >> I GOING TO LEAP AHEAD OF THE WAY MARK WANTED TO ORCHESTRATE THIS SINCE THERE'S SCENARIO TWO. I'M NOT SURE I FULLY INFORMATION IT AND MAYBE MISSED THE SUBCOMMITTEE'S MEETING ON IT. I DON'T FULLY UNDERSTAND WHY USING THE APP FOR A NEW PURPOSE WOULDN'T HAVE TO BE PART OF WHAT THE IRB CONSIDERED AND CONVEYS TO SUBJECTS MUCH LIKE THE LANGUAGE TOWARDS THE END OF SCENARIO THREE SAYING WHAT MIGHT GO NOT CONSENT FORM MARK COULD YOU WALK US THROUGH THE RECOMMENDATIONS FOR SCENARIO TWO ARE THERE TO SEE IF WE AGREE. >> LET ME GIVE MARK AND DAVID THE OPTION OF WHETHER YOU WANT TO. WE'LL GET TO THAT AND GET TO THE RECOMMENDATIONS I ASSUME CASE BY CASE. I DON'T KNOW IF YOU WANT TO STAY -- THAT WILL BE DISCUSSED. >> I THINK WE CAN ADDRESS THAT. I'M HEARING ROUGHLY CONSENSUS HERE AS A DID AT THE LAST MEETING ABOUT THE FIRST SCENARIO. I THINK WE'RE ON WHAT NANCY HAS BEEN TALKING ABOUT AND IT'S OKAY TO TALK ABOUT THAT NOW FROM MY POINT OF VIEW. >> LET'S DEAL WITH THE FIRST ONE. I DON'T KNOW WHAT THE DIFFERENT FEELINGS ARE IN TERM OF WHAT LESLIE BROUGHT UP. >> THE ISSUE OF ONE'S RISK IN SHARING DATA IS PRETTY UBIQUITOUS AND IT STRIKES ME WE COULD SAVE A LOT OF TROUBLE NOR IRBs IF THERE WAS ONE PLACE WHERE THERE WAS ONE GENERALIZED STATEMENT WITH THE RISKS OF SHARING DATA IN RESEARCH THAT THE IRBs OR VARIOUS DOCUMENTS COULD POINT TO SAYING FOR MORE INFORMATION ABOUT RISK THOINS TOPIC GO TO A -- RISK ON THIS TOPIC GO TO X, Y, Z AND WE WOULDN'T HAVE TO BEAT OURSELVES OVER THE HEADS ABOUT THIS. >> DOES OHRP WANT TO TAKE THAT ON THE EDUCATIONAL WEBSITE? I THINK IT'S A GREAT IDEA. SANDY. >> IN THE FIRST SCENARIO IF THE STUDY IS ASKING THEM TO USE AN ASPECT OF SAY FITBIT OR SOME OTHER WIDELY USED APP, THEY HAVE NOT BEEN PREVIOUSLY USING, THEY ARE POTENTIALLY UNDERTAKING -- THEY'RE CREATING DATA WHICH FITBIT IS GOING TO SELL AND SHARE WIDELY THAT MIGHT OTHERWISE NOT BE AVAILABLE TO pMEANS PEOPLE HAVE TO GO TO A LOT OF TROUBLE TO MAKE THEM READ IT AND SIGN IT OVER AGAIN. I THINK SIMPLY BY SAYING YOU USE THIS FEATURE OF FITBIT YOU'LL BE COLLECTING DATA WHICH FITBIT WILL USE IN ITS NORMAL WAYS AND I THINK ADDING THAT TO THE CONTENT FORM IS NOT AN UNREASONABLE THING. DOES THAT RESPOND TO YOUR -- >> IT SEEMS WHAT YOU'RE DESCRIBING IS ACTUALLY NOT SCENARIO ONE. I THINK IT'S MORE SCENARIO TWO. >> THAT GETS TO SKIP'S POINT WHETHER THE DATA COLLECTED IS DIFFERENT. IF YOU'RE USING IT FOR A DIFFERENT PURPOSE THAT'S ONE USE. IF THERE WAS DATA YOU WERE USING BEFORE OR HAD IT TURNED OFF IT WILL BE APP DEPENDENT. SUDDENLY THE MANUFACTURER HAD ACCESS TO DATA THEY DIDN'T HAVE BEFORE IS A DIFFERENT SCENARIO. I THINK THAT WOULD KICK IT OUT OF TWO. REMEMBER THE MANUFACTURER IS INVOLVED IN THIS. IN THE FIRST SCENARIO THE RESEARCHER IS USING DATA IN THE NORMAL COURSE OF THE APP AND IN THE NEW USE OF THE CONSUMER APP BUT THE MANUFACTURER IS NOT INVOLVED IN THE STUDY. IS NOT FUNDING IT OR DOING ANYTHING WITH IT. THERE MAY BE A SIDE BENEFIT TO THE MANUFACTURER BUT NOT BECAUSE IT PLANNED ON THAT OR INSTIGATED IT. YOU COULD HAVE HAD THAT OPTION. IT PUTS THE BURDEN ON THE INVESTIGATOR TO EXPLAIN IF YOU TURN ON FEATURE THIS IS WHAT WILL HAPPEN BUT TO SOME EXTENT YOU COULD ARGUE THE DATA USE IS THE SAME BUT THE USE IS DIFFERENT THAN INTENDED OUTSIDE THE RESEARCH CONTEXT I WOULD ARGUE IT'S NUMBER TWO. IF WE NEED THAT CLARIFIED WE HAVE TO GET NOT NUANCES WHICH IS DIFFERENT AND THEY SHOULD KNOW IF YOU TURN ON YOUR FEATURE AND NEED TO KNOW IT'S THE APP FEATURE BECAUSE IT'S A FEATURE THAT DOES NOT EXIST. >> THE DOCUMENT SAYS WE DON'T MEAN FOR THESE EXAMPLES TO BE ALL INCLUSIVE OR PERFECT. I THINK WE SHOULD DECIDE STRATEGICALLY HOW WE WANT TO -- I GO BACK TO THE QUESTION ABOUT THE PROTOCOL, I'VE SEEN PROTOCOLS WHERE YOU USE AND WHERE THE IRB REQUIRED THE STUDY PROVIDE PARTICIPANTS WITH A SEPARATE I PHONE BECAUSE IT GETS COMPLICATED. AND MAKE CLARIFICATION THAT PEOPLE WHO ARE CONCERNED WITH WHAT WE'RE RAISING CAN FIND THE S IN THE DOCUMENT. WALTER. >> I MAY BE TRANSGRESSING FROM THE REMARKS YOU JUST MADE, STEPHEN, BUT I WAS STRUCK BY AND THERE MAY BE UNINTENDED CONSEQUENCES OF PARTICIPATION. FOR EXAMPLE, THERE WAS AN ARTICLE IN THE PAPER JUST YESTERDAY ABOUT THE USE OF A SEARCH ENGINE, ONE OF THE MOST COMMON SEARCH ENGINES FOR PURPOSES OF LAW ENFORCEMENT WHERE THE APPS TRACK INDIVIDUALS BY GPS. WHICH MAY HAVE UNINTENDED CONSEQUENCES TO THE USER AND IT MAY SPEAK TO JANET'S PROPOSAL AROUND INCREASING AWARENESS AROUND SOME OF THE POTENTIAL UNINTENDED APPLICATIONS OF THE APPS, IF YOU WILL. >> THE QUESTION IS THEN WHO BEARS THE BURDEN? I THINK IT GOES BACK TO THE PROTOCOL QUESTION AND THE INVESTIGATOR SHOULD HAVE THE UNINTENDED CONSEQUENCES IF THEY USE THE APP THAT'S SAME OR DIFFERENT UNDER ONE OR TWO OR THREE FOR THEIR JOINT RESPONSIBILITY BECAUSE THEY'RE WORKING TOGETHER. I WOULD ARGUE IN THE PROTOCOL AND WE COULD ADD A SENTENCE THAT WOULD SAY SOMETHING LIKE SURE, THERE COULD BE OTHER CIRCUMSTANCES WHERE THERE COULD BE AN IMPACT ON THE WELFARE OF THE RESEARCH PARTICIPANT IN THE UNINTENDED WAY AND THE RESEARCHER SHOULD UNDERSTAND AND COMMUNICATE THE COMPLEXITY OF THE ISSUES. DON'T WORDSMITH IT IN THE PROTOCOL SO THE IRB CAN EVALUATE IT. THE BURDEN OUGHT TO BE ON THE INVESTIGATOR TO UNDERSTAND THAT AND KNOW THE IMPLICATIONS. THEN THE IRB CAN JUDGE ALONG WITH THE INVESTIGATOR WHAT NEEDS TO BE COMMUNICATED OR NOT. UNDER THESE SCENARIOS. I SUGGEST YOU TRY TO PUT A SENTENCE IN THAT SHOWS COMPLEXITY BUT I AGREE NOT GETTING INTO EVERY LITTLE POSSIBILITY HERE WE COULD BE HERE FOR A LONG TIME COMING UP WITH EXAMPLES. >> SO BEFORE WE GO TOO FAR INTO THIS, JUST LET'S CONSIDER SCENARIO ONE. SO SOMEONE HAS AN APP AND HAVE A FITBIT AND APPLE WATCH OR SOMETHING THEY'RE USING ALREADY. THEY HAVE AN iPHONE WITH THE APP IN EXACTLY THE SAME WAY THE RESEARCHER ARE USING IT. THEY HAVEN'T READ THE EULA. WE KNOW THEY HAVEN'T READ THE EULA. DO WE FEEL WHERE LIKE JUST BY DOING RESEARCH WITH THAT DATA WE'RE SOMEHOW COMPLICIT BUT THEY MADE THE DECISION TO DO THIS. JUST SCENARIO ONE, HOW DO PEOPLE FEEL ABOUT HOW THE RESEARCHER SHOULD BE CALLING OUT THE RISKS OF THE EULA FOR SOMETHING SOMEONE ALREADY HAS AND USES THE WAY THEY DO IN THE RESEARCH? >> IS THE RESEARCHER OBTAINING THE INFORMATION FROM THE APP? IN OTHER WORDS THEY HAVE THE APP ON THERE BUT NOW THE RESEARCHER WILL GO TO THE APP OPERATOR AND SAY PLEASE GIVE ME X INFORMATION. DO THEY HAVE PERMISSION? ONE SCENARIO IS SOMEONE'S JUST USING AN APP IN A NORMAL WAY. AS A RESEARCHER YOU NOTE THEY'RE DOING THAT AND MAYBE ASK QUESTION DOING THAT AND I DON'T KNOW, OBSERVE THEIR BEHAVIOR IN SOME WAY. SO YOU'RE NOT INTERATING WITH THIS AT ALL. THE OTHER IS YOU OBTAIN INFORMATION FROM THIS APP FOR WHICH YOU HAVE TO GO TO THE PERSON WHO OPERATES THE APP TO OBTAIN IT. >> I WOULD MAKE THE ASSUMPTION THEY GO TO THE MANUFACTURER. THE RISK OF THE SHARING OF THE DATA WOULD BE THE CONSENT AND THE RESEARCH DATA AND DOWNLOAD IT AND FROM THERE IT'S THEIR RESPONSIBILITY. BY THE WAY, THAT IS ALREADY COVERED IN THE EULA SO YOU DON'T HAVE TO WORRY ABOUT IT. I'M KIDDING. THAT'S THE MOST COMMON SCENARIO THEY GO TO THE MANUFACTURE TORE GET THE DATA -- MANUFACTURER TO GET THE DATA AND IT'S WHAT THE MANUFACTURER DOES WITH IT THAT'S OF CONCERN. >> I THINK THAT'S CORRECT IN MOST CASES. IN EITHER CASE, IN SOME CASES ONE CAN IMAGINE THE INDIVIDUAL HAS AN APP OR THE APP HAS A DATA PRODUCTION ITSELF AND SO WHEN THE STUDY SUBJECT COMES IN 30 DAYS LATER AT THE DATA COLLECTION POINT THE SUBJECT SIMPLY HANDS THE iPHONE TO THE RESEARCH COORDINATOR AND RESEARCH COORDINATOR WIPES DOWN THE DATA AND THAT'S THE LOW TECH WAY OF DOING IT AND IS POSSIBLE THAT COULD HAPPEN. THE MORE COMMON SCENARIO IS WHEN THE APP IS BEING USED EXACTLY FOR WHAT THE PERSON WAS YOU'VE IT FOR ANYWAY, NEVERTHELESS THE WAY TO GET IT IS GO TO THE MANUFACTURER AND PRESENT THE CONSENT FORM AND SAY WOULD YOU PLEASE GIVE ME THE DATA. I HAVE A STUDY GOING ON SO I NEED THIS DATA AND HAVE THE CONSENT OF THE INDIVIDUALS FOR YOU TO GIVE ME THEIR DATA. AND SOME GO ON A DROID AND iPHONE AND GETTING THE DATA. >> THIS IS BRINGING UP QUESTIONS FOR ME. SORE TRY TO COMPLICATE THINGS. RIGHT NOW THE WAY CURRENT CONSENTS ARE RIT JEP IT'S DIFFICULT -- WRITTEN IT'S DIFFICULT FOR A RESEARCH TORE TAKE DATA ALREADY COLLECTED BY AN IRB AND SHARE IT WITH ANOTHER AGENCY WITHOUT THE PATIENT'S PERMISSION. NOW WE'RE SAYING IT'S OKAY FOR THEM TO TAKE DATA THAT THEY KNOW IS GOING TO BE COLLECTED IN THEIR RESEARCH BUT BY THE VIRTUE OF THEIR COLLECTING IT, IT'S GOING TO BE AVAILABLE TO THAT APP AND ANYBODY ELSE THEY WANT TO SHARE IT WITH WITHOUT SAYING ANYTHING AND THAT SEEMS CONTRADICTORY TO ME. >> THAT'S WHY I WANTED TO START WITH ONE. IF THERE'S FAULT LIES IN ONE WE NEED TO ADDRESS THOSE AND THE OTHER SCENARIOS ARE MORE COMPLEX. >> SO GOING BACK TO ONE. "THE NEW YORK TIMES" CAME OUT WITH AN ARTICLE THAT STATE WHAT THE RISKS ARE OF SHARING THEIR DATA. I THINK FOR SCENARIO ONE IF WE JUST GIVE PEOPLE A PLACE TO GO AND LEARN MORE INFORMATION ABOUT WHAT MIGHT BE DIFFERENT BECAUSE THEY'RE CHOOSING TO USE THE DATA TIRE ALREADY COLLECTING IN RESEARCH. IF THEY HAVEN'T READ THE TERMS OF SERVICE THEY PROBABLY WON'T READ THAT EVER. THEY MADE THAT CHOICE. >> IN SCENARIO ONE WE'RE USING THE RESEARCH AND HOW IS THAT DIFFERENT FROM ABSTRACTION? YOU'RE COLLECTING THE DATA FOR CLINICAL CARE AND IN TERMS OF CONSENT, YOU'RE USING DATA COLLECT FORD A DIFFERENT PURPOSE AND NOW FOR RESEARCH AND OUTLINE THE RISKS IN THE CONSENT. >> THERE ARE SOME ISSUES AMONG PATIENTS WITH THAT IT'S NOT THE EPIC MANUFACTURER BUT THE OTHER GUY. THEY NOUNCED THEY'D START MONETIZING PATIENT'S DATA. I'M IN SOONER AND NOBODY ASKED ME. THAT ISSUE IS STILL THERE. >> TO KEEP US ON TOPIC, THIS IS NOT DATA FOR SCENARIO ONE. THEY'RE ALREADY COLLECTING IT. THERE'S NOT NEW DATA. SO I THINK THE INTENTION OF SCENARIO ONE IS THERE IS NOT A NEW RISK, NOT NEW DATA BEING COLLECTED. NOT NEW USES. THERE'S NOT NEW EXPOSURE TO THE MANUFACTURER. THERE'S DATA BEING COLLECTED BEING COLLECTED ANYWAY THAT THE SUBJECT PROBABLY IN AN UNINFORMED WAY AGREED TO AND THE ONLY CHANGES THAT DATA IS BEING NOW DOWNLOADED OR ACQUIRED BY THE RESEARCHER SO THERE'S ALL THE TYPICAL RESEARCH DATA RISK THAT WE SEE IN ALL STUDIES. THE RISK IN THE MANUFACTURER HAVING THE DATA WAS ALREADY THERE. THE QUESTION IS IS THIS SCENARIO SUFFICIENTLY DIFFERENT. WE'LL GET BACK TO OTHER THINGS. I DON'T MEAN TO MINIMIZE THEY'RE COMPLICATED BUT IT'S A FUNDAMENTAL ISSUE IF WE FEEL RESEARCH JUST USING EXISTING DATA FOR RESEARCH THE INDIVIDUAL ALREADY AGREED TO PROVIDE THROUGH THE EULA WHERE YOU'RE NOT ADDING RISKS THEY'LL BE EXPOSED TO BY THE MANUFACTURER, YOU'RE ONLY ADDING RISKS THAT WILL BE SKOEFD TO BY THE RESEARCH TEAM WHICH ABSOLUTELY SHOULD BE COVERED IN THE CONSENT. WHETHER WE NEED TO READDRESS THE RISKS THEY'RE EXPOSED TO BY THE MANUFACTURER HAVING THAT DATA JUST BECAUSE YOU'RE NOW USING THE SAME DATA FOR ANOTHER PURPOSE FOR WHICH THEY'VE CONSENTED. >> STEVEN, CAN I GO TO A -- STEPHEN, CAN I GO TO A HIGHER LEVEL OF WHAT YOU JUST SAID TO PUT IT ALL IN CONTEXT? SO YOU KNOW, I HAVE NO PERSONAL NORMATIVE VIEW OF WHAT ANY OF THIS SHOULD BE. I'VE JUST BEEN TRYING TO REFLECT AND SO HAS DAVID BORASKY AND FORRESTER AT THE SUBCOMMITTEE LEVEL AND THE DISCUSSION LAST TIME BUT SO YOU UNDERSTAND THE BASIC -- YOU GUYS ARE CONCENTRATED ON RISK, I DON'T DISAGREE WITH THAT. BUT WHAT WE HEARD A LOT OF AT LEFT IN THE SUBCOMMITTEE AND HEARD SOME OF IT LAST TIME IN THE SACHRP MEETING WAS PEOPLE WHO OPERATE IRBs SAY THE FOLLOWING, I CAN'T READ A TERMS OF SERVICE. I DON'T HAVE EXPERTISE IN TERMS OF SERVICE. THEY AGREE TO THEM ANYWAY AND AGREE TO THE CONTRACT IN THE BALLPARK WHEN THEY GO IN BUT WE DON'T READ THAT AND YOU'RE PUTTING AN IN FUR -- AN UNFAIR BURDEN ON IRBs AND THAT WAS THE GENESIS OF TRYING TO PUT THIS CONTINUUM OF RISK TOGETHER IN THE FOUR SCENARIOS TO TRY TO CALIBRATE THE DEGREE OF OVERSIGHT AND INTERVENTION BY THE RESEARCHER AND IRB TO THE DEGREE OF NEW RISK PRESENTED BY THE USE OF THE APP. I JUST WANTED TO SAY IN GENERAL BECAUSE WITH ALL THE RISK, THAT'S SIGN, BUT WE HAVE HAD MANY COMPLAINT OF IRBs AND RESEARCHERS WOULD HAVE A HARD TIME OPERATIONALIZING THIS WHEN THE MANUFACTURER IS NOT AT ALL INVOLVED IN THE RESEARCH. WE'RE NOT TALKING ABOUT WHERE SOMEONE IS USING FACEBOOK OR WHATEVER. AND THERE'S NO OPERATOR OR DEVELOPER BECAUSE THEY'RE ALREADY SCRAPING WHAT IS PUBLIC ON THE INTERNET WHICH PRESENTS ITS OWN SET OF CHALLENGES BUT WE'RE TALKING ABOUT WHERE THE APP OPERATOR IS INVOLVED IN SOME DEGREE AND HAS TO PROVIDE THE DATA TO THE RESEARCHER. IS THAT TRUE? WE'RE NOT TALKING ABOUT THE SITUATION IN WHICH THERE IS NO NEED FOR INTERACTION BETWEEN THE APP. >> IF THAT'S TRUE LET'S GET BACK TO THE CASE WHERE THAT HAS TO BE PROVIDED. LINDA THEN LEGACY. -- LESLIE. IT SEEMS TO ME FROM EXPERIENCE IT SEEMS LIKE HAVING TO REVIEW THE EULA WOULD HAVE TO BE BURDENSOME FOR THE IRB AND NOT ABLE TO NEGOTIATE THAT IN MANY CASES. ONE OPTION I THINK WOULD BE IF POSSIBLE IF WE COULD DEVELOP SOME SIMPLE LANGUAGE THAT POTENTIAL POTENTIALLY COULD BE PUT IN THE CONSENT FORM THAT WOULD CALL OUT THE RISKS ETCETERA AND THEN THAT WAY IT WOULD BE CLEARER FOR WHAT WE'RE TALKING ABOUT BECAUSE I DO THINK RESEARCH PARTICIPANTS DO NEED TO UNDERSTAND THAT THOUGH THEY'RE COLLECTING IT ANYWAY IT'S BEING USED FOR A NEW OR DIFFERENT PURPOSE AND THIS IS A REMINDER WHAT THE RISKS COULD BE AND THAT COULD ADDRESS THE CONCERNS RAISED THAT'S HOW I WOULD VIEW NUMBER ONE. >> I DON'T THINK THE IRB NEEDS TO LOOK AT THE RISKS IN SCENARIO ONE OR THE EULA. AND I HAVE A FITBIT AND DID NOT READ THE EULA. BECAUSE THERE'S PROMISES MADE WITH CONFIDENTIALITY WITHIN THE CONTEXT OF THE RESEARCH, THAT WE DON'T WANT -- WE WANT TO BE CLEAR ABOUT THAT. I THINK WHAT LINDA WAS GOING TO IS WHAT I WAS THINKING ABOUT AS WELL WHICH IS WE'LL TREAT WHAT YOU GIVE US BECAUSE THERE MAY BE OTHER THINGS YOU'RE GIVING US AND PROTECT THE CONFIDENTIALITY BUT YOU MAY HAVE AGREED OR THERE MAY BE AN AGREEMENT WITH THE MANUFACTURER OF THE FITBIT TO ALLOW THEM TO USE IT IN DIFFERENT TERMS AND THAT LANGUAGE TO BE CLEAR WHAT PROMISES WE'RE MAKING MAY BE DIFFERENT THAN WHAT FITBIT CAN DO AND WHATEVER COMES UP. IN THE WORLD WHERE THEY'RE USING IT IN WAYS PEOPLE DIDN'T ANTICIPATE. WE ALERTED YOU TO THAT AGREEMENT NOT WITH ACTUALLY GOING IN AND LOOKING AT THAT AGREEMENT. >> I'D BE CONCERNED IF WE PLACED RISK ON SCENARIO ONE AND TWO. THERE'S A DISTINCTION BETWEEN THE RISKS OF USING AN APP WE'RE ALL AWARE IN TERMS OF SOCIAL MEDIA ETCETERA AND WE SHOULDN'T PUT A BURDEN ON RESEARCH IF THERE'S NO CHANGE THANE RISK TO EDUCATE THE PEOPLE ABOUT THOSE RISK ARE SEPARATE FROM THE RISK IN RESEARCH. I THINK THAT'S A DIFFERENT TAKE. I'M NOT DISAGREEING THERE COULD BE A ISSUES AROUND THE USE OF DATA IN SOCIETY BUT WE SHOULDN'T PLACE THE BURDEN ON THE RESEARCHER AND IRB TO FIX THAT. >> LET ME MAKE ANOTHER CLARIFYING SUGGESTION. IN SCENARIO ONE, DATA IS BEING COLLECTED THE EXACT SAME DATA. THE RISK AND EXPOSURE AND CONFIDENTIALITY PROTECTIONS RESULT FROM THE RESEARCHER GETTING ACCESS TO THAT DATA AND USING IT ARE ABSOLUTELY HAVE TO BE DISCLOSED IN THE CONSENT FORM. SO THE QUESTION IS WHETHER IT'S IN THE CONCEPT FORM, RESEARCHER, IRB READING THE EULA. WHETHER ANY OF THAT IS NECESSARY IF THEY'RE ALREADY USING IT AND WE SHOULD BE VERY CLEAR THE ADDITIONAL RISKS TO CONFIDENTIALITY THAT RESULT FROM THE RESEARCH USE ABSOLUTELY NEED TO BE DISCLOSED AND THEY'RE KEEPING IT IN A FILE CABINET NEEDS TO BE DISCLOSED BUT WHAT WHAT HAPPENS TO THE DATA GOOGLE GETS ANYWAY WHAT HAPPENS TO THE AND IT HAS TO BE ADDRESSED AND LESLIE'S SUGGESTION IS A COMPROMISE. WE DON'T HAVE TO READ IT JUST REMIND PEOPLE THAT CONTINUING TO USE YOUR FITBIT, WHICH YOU'LL DO WHETHER OR NOT YOU SIGN THIS CONSENT FORM, CARRIES CONFIDENTIALITY CONSEQUENCES. I DON'T FEEL THERE'S A RIGHT ANSWER TO THAT BECAUSE IT GOES DOWN TO WHAT YOU THINK THE ROLE OF THE RESEARCHER IS. THAT'S THE QUESTION. THERE SHUNT BE ANY QUESTION. ALL THE RISK RESULT FROM USE OF THAT DATA AND DOWNLOADING THAT DATA BY THE RESEARCHER ABSOLUTELY HAVE TO BE COVERED AS THEY ALWAYS HAVE. THAT'S NOT AN ISSUE AND ONE OTHER CLARIFYING POINT, THE DOCUMENT USE THE WORD REVIEW, THE IRB HAS TO REVIEW THE EULA. I THINK WE NEED TO BE CLEAR WHETHER THAT MEANS READ OR TAKE ACTION ON AND APPROVE. I THINK FROM A RISK POINT OF VIEW IT'S REASONABLE TO SAY THE IRB REVIEWS THE YOU LA AS PART OF THEIR RISK MITIGATION STRATEGY AND THAT MAY BE DISCLOSURE IN THE CONSENT THAT DOESN'T IMPLY DIRECTLY THEY HAVE TO APPROVE IT OR MODIFY IT OR ANYTHING ELSE. BUT I THINK IRBs WOULD RATHER NOT READ THIS IF THEY DON'T HAVE TO AS WE ALL WOULD RATHER NOT READ WHICH IS KIND OF THE FUNDAMENTAL PROBLEM. THEY'RE WRITTEN TO DISCOURAGE US FROM READING THEM. THE SAME RESEARCH INFORMATION RISKS HAVE YOU FROM ANY OTHER DATA SOURCE HAVE TO BE DISCLOSED LIKE MEDICAL RECORDS. THE POINT OF VIEW EXPRESSED AND THIS IS CONTRARY TO THE SUGGESTION LESLIE MADE BUT I CAN'T UNDERSTAND WHO'S TALKING ALL THE TIME, IN THE BALLPARK SCENARIO OR IN RESEARCH THAT'S DONE WITH CARS, WE DON'T THINK IRBs AND RESEARCHERS NEED TO ALERT THEM TO THE FACT THERE'S PRE-EXISTING RELATIONSHIPS THAT'S NOT TYPICALLY DONE. THE QUESTION IS ASKED IF IF WE DON'T ALERT PEOPLE TO THE BACK STORY WHY DO WE NEED TO DO THAT HERE? >> THINK THAT'S EXACTLY RIGHT. THAT'S THE QUESTION. YOU I THINK WE DO BETWEEN THE STRONG CONFIDENTIALITY ISSUES OF PEOPLE IGNORE IN THE EULAS AND THE CONFIDENTIALITY DISCUSSION IN THE CONSENT FORM FOR THE RESEARCH USE OF THE DATA AND THAT DOESN'T EXIST IN THE BALLPARK SITUATION. I THINK THIS CAN BE DONE WITH ONE SENTENCE. AS LINDA AND LESLIE WERE SAYING. AT THE END OF THE DISCUSSION OF THE RISKS TO CONFIDENTIALITY AND THE PROMISE OF PARTIAL PROMISE IN THE CONSENT FORM YOU SAY SOMETHING LIKE REMEMBER THE DATA WE ARE KEEPING CONFIDENTIAL ARE STILL BEING COLLECTED AND USED BY THE APP MAKER SO IF YOU WANT TO GO BACK AND READ THE EULA, DO IT. SOMETHING THAT SIMPLE AND WE CAN STANDARDIZE THIS FOR EACH OF THE RECOMMENDATIONS THAT IS STRAIGHTFORWARD AND SIMPLE. >> TAUNTON AND THEN CONSUELO AND THEN SKIP. >> JUST TO CLARIFY THEN. THAT LANGUAGE WOULD BE NOR FIRST SCENARIO. WOULD WE DO THIS FOR THE ORGANIZATION THAT MAINTAINS IT OR OWN IN THE SCENARIO IN APPS, FITBITS AND THINGS LIKE THAT? THERE'S MANY SOURCES INFORMATION MAY COME FROM WHERE THE OWNER OR SOURCE OF THE INFORMATION COULD BE SHARING IT FOR DIFFERENT PURPOSES NOT RELATED TO THE. I WOULD THINK IN MANY CASES WE WOULD NOT BE REMINDING THEM OF THE PRIVACY PRACTICES OF THE SOURCE OF THAT INFORMATION. I'M TRYING TO UNDERSTAND WHY THIS IS DIFFERENT FROM THOSE SITUATIONS. >> IT'S DOCUMENTS FOR PEOPLE OUT THERE TO READ AND AGREE TO AND THE NOTICE OF PRIVACY PRACTICES EVERYBODY GETS ON A REGULAR BASIS MAY BE A DIFFERENT THING. SOMETHING LIKE THAT MAY BE A WISE THING TO DO BUT NOT IN THE SCOPE OF THE INVESTIGATION BUT MAY BE GOOD TO ADDRESS IN SIMILAR KINDS OF WAYS. FOR THE FIRST SCENARIO I THINK THE FINAL POINT OF THE RECOMMENDATION I AGREE THE IRB DOES NOT NEED TO REVIEW THE EULA OR TERMS OF SERVICE. I'M NOT SURE THE REFERENCE TO THE REGISTRY IS AND MINIMAL RISK SHOULD BE INCLUDED THERE. IF THEY'RE DOWNLOADING DATA FROM THEIR FITBIT AND TRANSFERRING TO THE RESEARCH TEAM WHICH IS HOW IT OFTEN HAPPENS, THERE MAY BE DATA IN THERE THAT COULD HAVE IDENTIFIERS AND PERSONAL INFORMATION. THEY COULD BE ACTIVITY MONITORING INFORMATION WHERE THEY WERE. TRANSFERRING SOME OF THAT INFORMATION MAY NOT MEET THE THRESHOLD FOR MINIMAL RISK. THE RECOMMENDATION DOESN'T TALK ABOUT THE RESEARCHER'S ROLE SHOULD BE THOUGH THAT'S SOMETHING WE'VE TALKED ABOUT. I'M NOT SURE HOW THE RESEARCHER WILL KNOW WHAT THE RISKS ARE IF THEY HAVEN'T READ THE EULA. >> I THINK THE RESEARCHER NEEDS TO UNDERSTAND EULA AND UNDERSTAND THE RISK IF THEY HAVEN'T, THEY AREN'T ABLE TO COMMUNICATE TO THE IRB. I DON'T THINK WE'RE TALKING ABOUT WHAT THE RESEARCHER SHOULD OR SHUNT UNDERSTAND. THEY -- OR SHOULDN'T UNDERSTAND. THEY SHOULD UNDERSTAND THE RESEARCH TO SAY TO THE IRB IT'S SCENARIO ONE, TWO, THREE OR FOUR. I DON'T THINK THIS HAS ANY IMPACT ON THE USE OF MEDICAL RECORDS ON ELECTRONIC HEALTH RECORDS OF WHICH THE MODIFICATION HAS ALREADY HAPPENED AND BEING BOUGHT AND SOLD ON THE MARKET. OFTEN IF YOU HAVE A RESEARCH THAT'S A CLINICAL TRIAL SUPER IMPOSED ON STANDARD OF CARE YOU'LL HAVE A SENTENCE LIKE YOU'VE ALREADY SPOKEN TO YOUR PHYSICIAN ABOUT X AND HE OR SEE HAS EXPLAINED WHY AND HERE'S WHAT WE PLAN TO DO BASED ON YOUR PREVIOUS AGREEMENT TO HAVE DONE Z. THAT'S IN MANY CONSENT FORMS THEN RESEARCH IS OTHER THAN STANDARD OF CARE. IN SOME SENSE WE'RE SAYING THE EULA IS STANDARD OF CARE HERE. YOU CAN REMIND PEOPLE THAT THEY AGREED TO THAT AND THEN JUST MOVE ON. WITHOUT NECESSARILY GOING INTO THE RISKS AND BENEFITS OF THAT PREVIOUS AGREEMENT. I THINK IT'S AN ANALOGOUS SITUATION. >> BEFORE WE GO BACK TO THE FUNDAMENTAL QUESTION, WE'RE INCHING TOWARDS A COMPROMISE. CONSUELO'S POINT THE REGISTRY DOESN'T REALLY FIT HOW DO PEOPLE FEEL? I TEND TO AGREE. WE HAVEN'T TALKED ABOUT THAT AT ALL FOR JUSTIFICATION FOR ONE OR THE OTHER SO I'M NOT SURE IT'S NECESSARY. >> I WOULD DELETE IT BUT WE COULD DEBATE THE POINT BUT IT'S TRAN -- TANGENTIAL. >> DOES ANYBODY FEEL IT SHOULD BE KEPT? >> I THINK IT'S NOT NECESSARY TO THE ARGUMENT. >> SO THERE'S NO OBJECTIONS TO REMOVING IT, MARK. >> I REMOVED IT. IT'S NOT NECESSARY IT'S FINE. >> THINK WE'RE AT THE POINT WHERE WE FOUND A FAULT LINE. SOME PEOPLE FEEL IN THE RESEARCH CONTEXT THE REGULATIONS REQUIRE TO US MAKE CONFIDENTIALITY DISCLOSURES IN THE CONSENT FORM. THROWS ARE ONLY RESEARCH USE OF THE DATA. I THINK SOME PEOPLE AND THINK IT'S A BELIEF OR A NORMATIVE BELIEF, I DON'T THINK WE'LL NECESSARILY CHANGE MINDS HERE. SOME PEOPLE BELIEVE THANE SCENARIO IT'S APPROPRIATE GIVEN YOU'RE DISCUSSING CONFIDENTIALITY TO POINT OUT TO PEOPLE THAT YOU HAVE, THIS IS WHAT WE'RE GOING DO BUT REMEMBER THERE ARE OTHER THANGS ARE GOING ON WITH YOUR DATA WE HAVE NO CONTROL OF YOU AGREED TO WHICH IS THE ONE SENTENCE SCENARIO. IT DIDN'T REQUIRE AN ASSESSMENT OF RISK OR IN THE CONSENT FORM. IT DOESN'T ADD TO THE WORK OF THE IRB. I SORT OF LIKE IT BUT I SORT OF DON'T BECAUSE IT'S MESSY IN A WAY. IT MAKE IT AN EXCEPTIONAL CIRCUMSTANCE BECAUSE WE'RE SENSITIVE TO DIGITAL DATA WHEN IT'S NOT THAT EXCEPTIONAL OF A CIRCUMSTANCE. NONETHELESS, I THINK THIS IS A REAL DIFFERENCE IN HOW PEOPLE FEEL ABOUT THIS. >> ARE WE MAKING AN ASSUMPTION INVESTIGATORS SHOULD READ EULAS AND BE KNOWLEDGEABLE AND I THINK IT'S A SLIPPERY SLOPE. I THINK IT'S A BURDEN TO BE EXPECTING THAT FROM INVESTIGATORS. >> I STARTED TO READ THE PRIVACY POLICIES WHEN I DOWNLOAD APPS IN LIGHT OF THIS BECAUSE I NEVER DID IT BEFORE. THEY'RE NOT OPAQUE. THEY'RE NOT MEANT TO BE READ EASILY BUT OUR EXPECTATION FOR A RESEARCHER IS SAYING THEY SHOULD USE A BLOOD TEST WITHOUT UNDERSTANDING THE FULL IMPLICATIONS OF THAT. PERSONALLY, IT'S NOT THE IRB. THEY'RE NOT DOING IT OVER AND OVER AGAIN SO IT'S A HUGE THING. WHEN YOU'RE USING A RESEARCH STUDY EXCLUSIVELY FROM A FITBIT I DON'T THINK YOU NEED TO BE COGNIZANT OF THAT BUT I MAY HAVE A HIGHER EXPECTATION OF INVESTIGATORS. >> I THINK IT MAY BE PAINFUL BUT I THINK IT'S GOING TO BE NECESSARY. IN A CERTAIN WAY, INFORMED CONSENT DOCUMENTS AS THE SACHRP IS DEEPLY AWARE HAVE BECOME EXTREMELY COMPLEX SUCH THAT I SUSPECT THAT SOME INVESTIGATORS FIND IT CHALLENGING TO WORK THROUGH INFORMED CONSENT DOCUMENTS. THE DISTINCTION BETWEEN ELECTRONIC MEDICAL RECORDS AND EULAS, WE HAVE THIS STRUCTURE OF DATA PRIVACY. IT'S TRUE IT'S MON TIEFD TIES -- MONETIZED BUT THERE'S SAFEGUARDS AND FOR EULAS, THEY'RE IN EFFECT NO SUCH REAL OVERSIGHT. THEY'RE TO EYE -- EYE DEM ANIFY THE USER TO FULFILL THE RESPONSIBILITIES FOR RESEARCH PARTICIPANTS. WE'RE >> >> WE'RE TALKING ABOUT PEOPLE USING AN APP AND POSTING AND THE POSTS ARE PUBLIC. THE RESEARCHER CAN OBTAIN THOSE POSTS WITHOUT THE INVOLVEMENT OF THE APP DEVELOPER OR OPERATOR AT ALL. AND THE PERSON HAS NO CONSENT OR NON-CONSENT. IT'S A DISTINCTION THAT APPLIES TO SCENARIO ONE WE NEED TO MAKE. I ALSO MENTION IT AS SOMEONE WRESTLING WIJT NOW. THERE'S -- WITH IT NOW. THERE'S NO CLEAR MANDATE FOR IRBs TO INTERVENE IN THE PROCESS THOUGH THERE'S EIGHT OF QUESTIONS WHETHER IRBs SHOULD INTERVENE FROM WHAT I SEE FROM AN INSTITUTION THAT DOES REQUIRE PEOPLE TO OBTAIN IRB APPROVAL FOR THIS KIND OF WORK, THERE'S PLENTY OF REASON TO TAKE A CLEAR AND CAREFUL LOOK AT IT. IT ALSO DOES INVOLVE MAKING SURE WHAT THIS RESEARCHER IS DOING IS CONSISTENT WITH THE TERMS OF SERVICE THE PERSON AGREED TO WHEN THEY MADE THIS INFORMATION AVAILABLE. I THINK THE DISTINCTION HERE RELEVANT TO SCENARIO ONE IS THIS IS A CASE WHERE THE DATA IS NOT OBTAINABLE INDEPENDENT OF THE APP OPERATOR WHERE THE RESEARCHER HAS TO GO TO THE APP OPERATOR IN ORDER TO GET THE DATA WHICH I THINK WE NEED TO EXPLAIN TO MOTIVATE WHAT SCENARIO ONE REALLY MEANS. I'D RAISE THE QUESTION WHETHER WE OUGHT TO SAY ANYTHING ABOUT SCENARIO ZERO AND I WISH WE WOULD BUT I DON'T THINK IT'S ON THE TABLE NOW. >> JANET, I THINK WE SHOULD TAKE IT OFF THE TABLE NOW BECAUSE IN THE ARGUMENT OF SCREEN SCRAPING FACEBOOK AND SUCH OR TWITTER OR WHATEVER, THE DATA ARE SHARED AND PUBLICLY AVAILABLE. WE MAY WANT TO ADDRESS THAT. I THINK WE SHOULD MAKE CLEAR THAT THAT'S NOT WHAT WE'RE TALKING ABOUT HERE. >> YOU SAID WHAT I WAS GOING SAY. WHEN PEOPLE POST WORDS ON FACEBOOK YOU KNOW WHAT DATA YOU'RE PUTTING OUT THERE. IT'S NOT THE SAME WITH A MEDICAL DEVICE. DON'T NECESSARILY KNOW WHAT DATA THEY'RE COLLECTING. I THINK THIS APPLIES TO DATA COLLECTED FROM DEVICES NOT PUBLIC POSTS. >> SO JUST A PROCEDURAL NOTE, MARK, I UNDERSTAND YOU HAVE TO LEAVE AT 10:30, CORRECT? >> THAT'S RIGHT, STEPHEN. >> YES. >> COULD WE GET CALENDAR -- CLOSURE ON SCENARIO ONE. >> YOU GUYS HAVE APPROPRIATELY IDENTIFIED A LOT OF FACTUAL SCENARIOS THAT EACH OF WHICH HAS SOMETHING DIFFERENT THAN WHAT'S EXACTLY IN SCENARIO ONE AND TWO AND THAT'S ALL WE DEALT WITH SO FAR. WE COULD DO A WHOLE DIFFERENT APPROACH TO THIS AND NOT HAVE SCENARIOS AND JUST HAVE PRINCIPLES. THE PRINCIPLES WOULD BE TRACKING THE PREMIUM THAT SAYS WHEN THERE'S AN APP USE SUBJECTS SHOULD ALWAYS BE ALERTED SO THE FACT THERE'S TERMS AND CONDITIONS IN APPS THEY SHOULD BE CONSULTED AND TO THE EXTENT THE MANUFACTURER OF THE APP OR CONTROLLER OF THE APP IS GOING TO DERIVE BENEFITS FROM THE STUDY AND INVOLVED IN THE STUDY OR SPONSORING OF IT, THERE SHOULD BE A GREAT ATTENTION TO THE TERMS OF SERVICE AND THE CONSISTENCY WITH THE COMMON RULE AND BELMONT REPORT AND WITH THE CONSENT FORM AND PROTOCOL. THREE WOULD BE THE PROTOCOL THAT RESEARCHERS SHOULD ALWAYS LOOK AT THE TERMS OF SERVICE BECAUSE THAT'S WHAT A RESEARCHER HAS TO DO WHEN HE OR SHE IS DESIGNING THE STUDY. WE COULD GO ON BUT THERE'S A WAY TO DO THIS. IT'S NOT SCENARIO BOUND. IF PEOPLE WOULD PREFER THAT WE COULD DO THAT. >> SO MARK, I WOULDN'T LOSE TO SCENARIOS BECAUSE I THINK HAVING CONCRETE EXAMPLE IS USEFUL TO PEOPLE AND I THINK PUTTING THE FRAMEWORK BEHIND IT AND USING THE SCENARIOS AS EXAMPLES WOULD CLARIFY BECAUSE I DO THINK WE'RE NOT GOING TO COME UP WITH CLEAN SCENARIOS THAT ENCOMPASS ALL POSSIBILITIES SO HAVING THE FRAMEWORK AND HAVING THE ILLUSTRATIVE EXAMPLES MAY BE THE BEST WAY TO DO IT. >> THAT'S THE WAY I ORIGINALLY DRAFTED THE MINI VERSION. THE SUBCOMMITTEE DIDN'T LIKE THAT BUT I'M HAPPY TO GO BACK. >> SKIP. >> YOU WOULD PROBABLY MAKE THAT PART OF THE CONCLUSION. YOU COULD SIMPLY IN CONCLUSION SAY HERE ARE THE THREE OR WHATEVER OR HOWEVERMAN -- HOWEVER MANY YOU COME UP WITH THE OPTIONS IN THE SCENARIO AND AS THE A WAY TO CONCLUDE RATHER THAN ISSUE GUIDANCE. SO WE HAVE 12 MINUTES. DOES ANYONE OBJECT TO MARK'S SUGGESTION THAT WE MOVE TO SUPPLEMENTING THE EXAMPLES WITH PRINCIPLES BEFORE OR AFTER? SO MARK, CAN YOU I WANT TO GIVE YOU AS MUCH AS POSSIBLE FROM THE MEETING TO TAKE THIS FORWARD. DO YOU WANT TO GO THROUGH THE PRINCIPLES? ARE THERE ANY YOU THINK WOULDN'T RESONATE THE ONES YOU DESCRIBED SEEM CONSISTENT. I DON'T THINK ANYONE WOULD OBJECT. IS THERE ANYTHING YOU WANT OUR OPINIONS BEFORE TAKING THIS BACK? [INDISCERNIBLE]. >> MARK, WE'RE LOSING YOU. CAN YOU REPEAT THAT? >> CAN YOU HEAR ME NOW? >> YES. >> WHAT I WAS SAYING IS I ARTICULATED THE OR FOUR PRINCIPLES JUST OFF THE TOP OF MY HEAD BASED ON THE CONVERSATION THIS MORNING. I THINK THE TIME THAT REMAINS IF PEOPLE HAVE IDEAS WHAT THEY'D LIKE TO SEE IN ADDITIONAL USE OF THE NEXT 10 MINUTES.GOOD >> READERS SHOULD READ THEM. PEOPLE SHOULD BE ALERTED TO THE FACT THAT THEY MADE PRIVACY COMMITMENTS TO PRIOR TO THE RESEARCH. THERE WAS A THIRD ONE. DOES ANYONE HAVE OTHER THINGS? >> THE THIRD ONE WAS BASICALLY THAT WHERE THE CONTROLLER OR MANUFACTURER OF THE APP IS GOING TO BENEFIT FROM IN SOME DEMONSTRABLE WAY OR THE RESEARCH OR THE COLLECTION OF RESEARCH FOR THE MANUFACTURER AND CONTROLLER IS INVOLVED IN THE DESIGN AND FUNDING AND/OR FUNDING OF THE STUDY THEN THERE OUGHT TO BE GREATER ATTENTION PAID BY THE RESEARCHER AND IRB TO THE TERMS OF SERVICE. >> OKAY. GOOD. SKIP. >> I WOULD ADD A PRINCIPLE THAT ARTICULATE THE RESEARCH RISK VERSUS APP RISK. SOMETHING ALONG THE LINES OF TRYING TO COMBINE SCENARIO ONE AND TWO TO SAY IF THERE'S NO CHANGE IN THE DATA BEING COLLECTED BY THE APP THEN THOSE WOULD NOT BE THE USE OF THE DATA WOULD NOT BE CONSIDERED RESEARCH RISK FOR THE PURPOSE OF REVIEWING THE TERMS OF AGREEMENT OF THE APP WITH THE CAVEAT THE CONFIDENTIALITY OF THE RESEARCHER WOULD STILL NEED TO BE ADDRESSED. SOMETHING LIKE THAT. >> I THINK REFERRING TO THE GENERAL PRINCIPLE OF IDENTIFYING WHAT THE NEW RISKS ARE WHICH IS CONSISTENT WITH WHAT SKIP IS SAYING AND SEEKING TO MITIGATE THEM AS ONE ALWAYS DOES CONSISTENT WITH THE BELMONT REPORT. AND SAYS WHEN YOU'RE WORK THE DEVELOPER YOU MAY BE ABLE TO TAKE EXTRA STEPS TO MITIGATE THE RISK AND TYING THEM TO THE BASIC PRINCIPLES WE ALWAYS TIE THEM WITH IS A GOOD WAY TO THINK ABOUT IT. >> IS IT WORTH HAVING A PRINCIPLE IN THERE IDENTIFYING HOW THIS APPLIES TO A DEVICE OPPOSED TO RESEARCHING ONLINE AND SOCIAL MEDIA? >> IT'S MY PERSONAL FEELING AND I'LL LEAVE THIS UP TO MARK IN HIS NEXT DRAFT WE SHOULD PUT LANGUAGE IN THAT EXCLUDE THAT SITUATION BECAUSE THAT'S A BIGGER TOPIC. BUT MAKING THAT EXPLICIT I THINK WOULD BE USEFUL. ANYTHING ELSE? CONSUELO. >> MAYBE IT'S INHERENT IN THE DESIGN OF THE CURRENT SCENARIOS BUT IT SEEMS WE'RE MAKE DISTINCTION BETWEEN INDIVIDUALS WHO ALREADY POSSESS THE APP AND THOSE WHO ARE ACQUIRING IT FOR THE RESEARCH. SO MAYBE THAT AS A PRINCIPLE OR A GUIDING PRINCIPLE THERE SHOULD BE A DISTINCTION BETWEEN HOW THOSE SHOULD BE APPROVED. >> WE SORT OF STARTED WITH THAT BUT I THINK THAT NED TO BE SURVIVE. LINDA, DO YOU STILL -- >> SORRY. I HAD A QUICK COMMENT ABOUT SCENARIO NUMBER FOUR. I JUST WANTED TO CLARIFY IN SOME SITUATION THE RESEARCHER MAY BE ACTUAL MANUFACTURER AND WE'VE BEEN TALKING ABOUT THAT IF WE COULD STRENGTHEN THAT TO MAKE THAT CLEAR BECAUSE SOMETIMES LATER ON I'M SURE WE'LL WORDSMITH THIS BUT IT TALKS ABOUT AND THE RESULT AND COLLECTED DATA ARE INTENDED TO PROMOTE THE COMMERCIAL INTEREST OF THAT ENTITY AND I WANT TO MAKE CLEAR SOMETIMES IT'S NOT THE AND THE RESULTS OF IT MAY BE MORE THAN JUST TO PROMOTE THE COMMERCIAL INTEREST OF THE ENTITY THAT COULD BE INTEGRAL TO THE RESEARCH AND WE WANT TO DISCLOSE THE RESEARCHER'S INVOLVEMENT IN THAT. THERE MAY BE OVERLAP THERE IF WE COULD STRENGTHEN THAT, THAT WOULD BE HELPFUL I THINK. >> JUST A QUICK QUESTION WITHOUT OPENING UP THE WHOLE MAN -- PANDORA'S BOX, COULD WE GIVE MARK A SENSE OF THE GROUP WITH A DIRECTION OF ALL FOUR SCENARIOS WHETHER WE'RE ON THE RIGHT TRACK. I THINK THE ANSWER IS YES. IS THAT SOMETHING WE CAN ACCOMPLISH WITHOUT GETTING INTO THE WORDSMITHING AND DETAILS OF EACH SCENARIO. >> SO SKIP HAS THROWN OUT A CHALLENGE TO THE GROUP. NANCY. >> ACTUALLY, THAT'S A GREAT SET UP FOR MY QUESTION WHICH IS I DON'T KNOW HOW TO PUT THIS IN TERMS OF A PRINCIPLE BUT I DON'T REALLY UNDERSTAND THE RECOMMENDATION AROUND SCENARIO TWO AND I WOULD LIKE US TO HAVE A LITTLE OPPORTUNITY TO UNDERSTAND WHAT'S GOING ON IN SCENARIO TWO BECAUSE I THINK IF THAT ONE CAN GO EITHER WAY THAN WE DON'T WANT TO GET TANG WILLED UP IN THIS -- TANGLED UP IN THE SAME DISCUSSION THE NEXT TIME WE SEE THE DOCUMENT. >> SKIP. >> LET ME GIVE A CONCRETE EXAMPLE. THERE'S A LOT OF INTEREST IN PEDIATRIC PULMONARY CONDITIONS AND THE ACTIVITY DATA IS GOING TO THE APP MANUFACTURER BUT THE APP MANUFACTURE'S NOT TRYING TO TIE THAT INTO THE CLINICAL ISSUES AROUND EXERCISE TOLERANCE AND WALKING AND THAT SORT OF THING. THERE'S NO IMPACT WHETHER IT'S FITBIT AND THEY'RE NOT TRYING TO ANSWER THAT QUESTION BUT THE RESEARCHERS ARE GETTING THE ANTIGRAPHY DATA AND THEY CAN LINK TO QUESTIONNAIRES AND WALKING AND SIX-MINUTE WALK TESTS AND SO ON AND SO FORTH. THE DATA'S THE SAME AND FITBIT'S COLLECTING THE DATA AND TO ME THAT'S I SCENARIO OF AN EXAMPLE. I DON'T SEE IMPACT OF THAT USE OF THE RESEARCH ON THE DATA FROM THE APP PERSON. YOU WOULD HAVE TO DISCLOSE WHAT THE RESEARCHER'S DOING. TO ME THAT'S AN EXAMPLE UNDER NUMBER TWO. >> SO SKIP, DOES THAT MEAN THE ACTIGRAPHY DATA MAY BE MORE ACCURATE HAN THE SIX-MINUTE WALK? >> YES. >> I GUESS IT. -- I GET IT. SO THE USE OF ACTIGRAPHY DATA TO DIAGNOSE PARKINSON'S. BECAUSE THE DATA'S THE SAME THE MANUFACTURER HAS IT, BUT NOW YOU'RE LABELLED MAYBE A DIAGNOSIS IS MADE AND MAYBE IN SOMEONE'S RECORD THEY'VE NOW CLASSIFIED YOU THIS WAY WITH THAT THAT IMPLIES FOR INSURANCE AND ACCESS AND EVERYTHING ELSE. >> STEPHEN, GO AHEAD -- >> THAT'S ALL. >> I THINK THAT'S NOT SCENARIO TWO BECAUSE SCENARIO TWO THE RESEARCHERS IS INDEPENDENT FROM THE RESEARCHER AND THEY'RE GETTING EXTRA DATA FROM THE MANUFACTURER AND WHETHER THERE'S PARKINSON'S OR NOT THAT'S A RISK. I WOULD CLARIFY THAT AS A RISK OF THE RESEARCH NOT A RISK OF THE APP. >> OKAY. I'M OKAY WITH THAT. >> SO WE HAVE THREE MINUTES LEFT. TO NANCY'S POINT, THE ONE SCRIPT DESCRIBED BETTER THAN I DOES -- THE ONE SKIP DESCRIBED BETTER THAN I DID, WHERE NOTHING CHANGES AT THE SERVERS AT GOOGLE, APPLE OR NIT FITBIT AND NOTHING CHANGES WITH WHAT THE APP MANUFACTURER OR CONTROLLER S -- HAS ACCESS BUT THE MANUFACTURER IS DOING SOMETHING DIFFERENT WITH THE DATA THAT YOU PURCHASED THE FITBIT FOR HOW DO PEOPLE FEEL WHETHER IT'S A SUBSTANTIVE CHANGE FROM SCENARIO ONE? I KNOW IT'S NUMBER TWO BUT THE RECOMMENDATIONS ARE BASICALLY THE SAME AS ONE WHICH IS WHAT NANCY HAD THE ISSUE WITH. >> STEPHEN, CAN I ARTICULATE THE REASON. NANCY WAS ASKING THE REASON WHY THE RECOMMENDATIONS IS AS IT IS FORESCENARIO TWO. I THINK REASONABLE PEOPLE CAN DISAGREE ABOUT THIS AND I DIDN'T WRITE THIS, DAVID FORRESTER INSERTED THIS PARAGRAPH AND THE ARGUMENT IS SOMEONE SIGNED UP FOR THE APP BEFORE THE RESEARC. THEY ALREADY AGREED TO THE TERMS AND CONDITIONS. IN DAILY LIFE APPS ARE USED IN DIFFERENT WAYS THROUGHOUT THE LIFE OF AN APP AND AN INDIVIDUAL. SO THE FACT THE APP MAY BE USED FOR A DIFFERENT PURPOSE FOR THIS PARTICULAR RESEARCH IS NOT DISSIMILAR TO THE USE OF AN APP IN REAL LIFE. THE PERSON ALREADY AGREED TO THESE THINGS ON HIS OR HER OWN KNOWING AS THE BACKGROUND KNOWLEDGE OF OUR LIVES THAT DATA COLLECTED IN ONE WAY COULD BE USED AND DATA COLLECTED IN ANOTHER AND THAT'S WHAT THE APP EULA SAYS. THEY USUALLY HAVE THE BROADEST POSSIBLE TERMS OF INVESTIGATION. THEREFORE IT'S NOT REALLY THOUGH THE DATA IS NOT USED IN A DIFFERENT WAY IT'S NOT MATERIALLY DIFFERENT FROM NORMAL TYPICAL DAILY CONDITIONS THE WAY APPS WILL TRANSPIRE AND DEVELOP AND USE THAT WOULD LEAD TO US A DIFFERENT CONCLUSION THAN SCENARIO ONE IS THE ARGUMENT. >> THANK YOU, MARK. I THINK THERE'S A NUMBER OF QUESTIONS. WE'RE RUNG OUT OF TIME. -- RUNNING OUT OF TIME AND WE'LL START WITH JODY AND DO AS MANY AS WE CAN BEFORE YOU ARE HAVE TO LEAVE. >> ARE YOU TALKING ABOUT DIFFERENT PURPOSE THAN THE DATA IS LOOKING AT? WHAT DO YOU MEAN DIFFERENT PURPOSE? >> TO TAKE AN EXAMPLE WE COULD GO BACK TO SKIP'S EXAMPLE IN PEDIATRICS BUT THE REASON ONE WOULD SIGN UP FOR A FITBIT IS BECAUSE IT WANTS TO UNDERSTAND HOW MANY STEPS ONE TAKES AND ONE'S EXERCISE PATTERNS AND TRACKING RESPIRATION AND HEART RATE AND THAT MAY BE USED IN SCENARIO TWO FOR A COMPLETELY DIFFERENT PURPOSE THAN THE DATA. THEY'RE EITHER COMPREHENDED AND ACTUALLY IDENTIFIED AND USED BY THE INDIVIDUAL EVEN THOUGH THE DATA WAS COLLECTED AND IT WASN'T THE PURPOSE FOR WHICH THE INDIVIDUAL WAS SIGNED UP FOR THE APP. IT'S A DIFFERENT PURPOSE TO UNDERSTAND A HEALTH CONDITION. >> CAN I GIVE AN EXAMPLE? SO MY FITBIT TRACKS MY SLEEP AND WHEN I FIRST BOUGHT IT IT TOLD ME THE HOURS WHEN I WENT TO BED AND GOT UP AND WAS RESTLESS. IN THE APP UPGRADE IT GIVES ME A NEW DISPLAY WHETHER I'M IN DEEP SLEEP OR REM OR REGULAR SLEEP AND GIVES ME A RATING OF WHAT THE QUALITY OF MY SLEEP IS. THAT'S NOT THE ORIGINAL PURPOSE. THAT'S NOT WHAT I SIGNED UP FOR, IT'S STILL COLLECTING THE SAME DATA BUT IT'S FIGURE THE OUT HOW TO USE THE DATA IN A DIFFERENT WAY. I THINK I'M AGREEING. I DON'T THINK THERE'S A BIG DIFFERENCE BETWEEN ONE AND TWO. >> AND I WANT TO UNDER SCORE TWO POINTS. THE FIRST IS SKIP ALLUDED TO THIS AND THERE'S A KEEN INTEREST IN PATIENT REPORTED OUTCOMES BEING REPORTED INTO PRODUCT LABELS AND THERE'S BEEN A LONG DIALOGUE BETWEEN THE AGENCY AND VARIOUS MANUFACTURERS AND INCORPORATING SUCH DATA. AND THESE APPS ARE POTENTIALLY A FOCUS OF SUCH DISCUSSIONS GOING FORWARD. IT'S NOT A TRIVIAL EXERCISE. THE SECOND ISSUE IS THE APP MANUFACTURERS ARE NOT WORKING IN BIOMEDICAL RESEARCH. THEY'RE COMMERCIAL ENTITIES DEVELOPING NOVEL APPLICATIONS THAT ARE OF INTEREST COMMERCIALLY. WE SHOULD BE ATTENTIVE TO THE LIKELIHOOD THE APP MANUFACTURER WILL BUY OTHER APP MANUFACTURERS AND THE EULA YOU SIGNED AT THE BEGINNING OF A STUDY MAY ACTUALLY THE APP MAY LOOK VERY DIFFERENT AT THE END OF THE STUDY. SO BEING ATTENTIVE TO STUDY AMENDMENTS IS ONE WE SHOULD ADDRESS. >> SO I'M BECOMING CONVINCED THAT IN SOME RESPECT SCENARIO ONE IS NOT VERY DIFFERENT FROM SCENARIO TWO AND MAYBE IT'S A TOTALLY OFF THE WALL PIECE OF THINKING BUT MAY BE SOMETHING PEOPLE WHO ARE BEING RECRUITED INTO A SCENARIO TWO STUDY MAY THINK ABOUT WHICH IS THE LIKELIHOOD THAT THE APP MANUFACTURER COULD REVERSE ENGINEER WHY THEY'RE COLLECTING INFORMATION AND MONETIZE THAT TO ADVERTISEMENTS FOR PARTICULAR CONDITIONS OR EVEN TO INSURERS BECAUSE OF THIS GAP THAT WALTER MENTIONED EARLIER BETWEEN SORT OF THE WORLD OF APPS AND EULAS AND THE PRIVACY PROTECTIONS FOR MEDICAL RECORDS THAT IT MIGHT MAKE IT EASIER FOR SOME APP MANUFACTURERS TO FIGURE OUT WHY THESE PARTICULAR QUESTIONS ARE BEING ASKED AND SAY, OH, THERE'S SOMETHING WE CAN DO WITH THE SAME DATA WE ALREADY HAVE. THIS IS A REALLY OUT THERE SCENARIO BUT IT MAY BE SOMETHING THAT WOULD INCORPORATE HOW WE -- THE LANGUAGE THAT WE CRAFT TO SUPPORT A RECOMMENDATION ABOUT SCENARIO TWO AND PROVIDE TO POTENTIAL RESEARCH SUBJECTS IN A CONSENT FORM. >> FIRST, I DON'T THINK IT'S OUT THERE ATTAL I THINK IF -- AT ALL I THINK IF THEY CAN DETECT AFIB IT WILL BE IN NEXT RELEASE AND A WONDER IF IT FALLS IN THE CAVEAT WHY WHERE WE'RE NOT SUPPOSED TO LOOK AT THE IMPLICATION. >> FOR INFORMATIONAL TERMS NOT NECESSARILY FOR RISK BENEFIT CALCULATION BECAUSE YOU'RE RIGHT. >> AS A PRACTICAL MATTER IT'S GOING TO BE DIFFICULT TO DISTINGUISH BETWEEN ONE AND TWO BECAUSE THE NOTION THE DIFFERENCE BETWEEN ONE AND TWO IS THAT YOU ARE INDUCE ING A PERSON TO ADD OR TURN ON A FEATURE THEY DIDN'T HAVE TURNED ON BEFORE. SOME PEOPLE WILL HAVE TURNED IT ON AND SOME WON'T HAVE TURNED IT ON AND SOME WON'T KNOW WHETHER THEY TURNED IT ON OR NOT. TO ME AS A PRACTICAL MATTER, ONE AND TWO WILL BE VERY DIFFICULT TO DISTINGUISH IN A FIELD STUDY OF ANY KIND. >> SO IF A SMART WATCH MANUFACTURER TRIES TO USE A GENERIC INSTEAD OF A BRAND NAME AND WORKS WAY SPONSOR OR ANOTHER RESEARCHER TO SHOW THE HEART MONITORING FEATURE IS USEFUL FOR DIAGNOSIS OF ATRIAL DEFIBRIL AND THAT BECOMES AN IN VITRO DIAGNOSTIC DEVICE IF THAT NEEDS APPROVAL IF THEY WANT TO LABEL AND MARKET FOR THIS SERVICE BUT I DON'T SEE A PROBLEM IF THEY WANT TO DID THAT AND LABEL AND MARKET FOR THAT PURPOSE. GOD BLESS, THEY SHOULD HAVE THE RIGHT TO DO THAT AND IF THEY DO THAT USING MY HEART RATE DATA SO BE IT. TO ME THAT COMMERCIALIZATION IS A GOOD THING NOT A BAD THING. AND I DON'T SEE ANY REASON WHY WE SHOULD DISCOURAGE THE MODIFICATION THAT'S TO THE BENEFIT OF PUBLIC HEALTH CHIN THIS CASE IT WOULD BE. >> A NUMBER OF PEOPLE HAVE THEIR TENTS UP. >> STEPHEN, I HAVE TO GO. >> IT'S PERFECT. IF YOU GET OFF QUICKLY THERE'LL BE NO MORE QUESTIONS. THANK YOU VERY MUCH. I THINK WE'RE AT A GOOD STOPPING POINT. THANK YOU. >> THANK YOU. BYE. >> BYE. SO ANTICIPATE WHEN WE COME BACK WE'LL START A PRINCIPLES DISCUSSION AND SEE IF THE SCENARIOS FIT. SO WE WERE SUPPOSED TO BE SCHEDULED FOR A BREAK IN EIGHT MINUTES. WE HAVE TWO ITEMS TO GET THREE BEFORE LUNCH BUT I THINK MAYBE A 10-MINUTE BREAK WOULD BE AN APPROPRIATE TIME. PARTICULARLY THE ONE ABOUT PARTICIPANTS SHOULD BE PAYING VERY QUICK. JUST KIDDING. >> QUESTIONS HAVE ARISEN, SOME PEOPLE HAVE ASKED IN TERMS OF WHAT THIS CURRENT RULES ARE WHAT'S OHRP'S TAKE ON THIS SO IN TERMS OF FULL DISCLOSURE, EULAS AREN'T OUR TOP PRIORITY IN TERMS OF GUIDANCE. WE'RE LIKELY NOT TO GET TO THIS ISSUE FOR A FAIRLY LONG TIME. WE HAVE A WRONG -- BACKLOG OF OTHER THINGS WE WANT TO WRITE GUIDANCE ABOUT BUT IN TERMS OF TOOLS AND I TALK ABOUT THE FIRST THREE SCENARIOS WHERE THE RESEARCHER BASICALLY HAS NO DIRECT INTERACTION WITH THE ENTITY THAT CREATED THIS APP, I THINK OUR CURRENT TAKE ON THOSE SCENARIOS IS THERE'S NOTHING IN ANYTHING WE'VE PUT OUT IN TERMS OF GENERIC GUIDANCE THAT WOULD SAY THAT IRBs HAVE TO BE READING EULAS AND TRYING TO UNDERSTAND THEM. IN FACT THERE'S REASONABLE ARGUMENTS IN TERMS OF HOW IRBs ARE CURRENTLY STAFFED AND THEIR PRIORITY AND IF YOU CAME TO OHRP IN THOSE THREE SCENARIOS, WE WOULDN'T BE REQUIRING THE IRBs TO READ THE EULA. IN TERMS OF THE DISCUSSIONS HERE THE POINT IN TERMS OF HAVING ONE SENTENCE AND THE PRIVACY AND CONFIDENTIALITY SECTION AND I'M INCLUDING SCENARIO THREE WHERE THE PERSON ENDS UP INTERACTING WITH THE APP AS PART OF THE RESEARCH EVEN THOUGH THEY WEREN'T OTHERWISE INTERACTING WITH IT IN THE SCENARIOS IT'S REASONABLE AND CONSISTENT TO HAVE SOMETHING IN THE SECTION WHICH AGAIN I THINK IS GENERIC AND NOT ALL THAT DISSIMILAR TO WHAT OFTEN HAPPENS. OFTEN THOSE SKSS DISCLOSE -- SECTIONS DISCLOSE THEY'RE GIVEN TO OTHER ENTITIES AND FOR LEGAL AND OTHERWISE AND THERE'S A DISCUSSION IN WHAT THE ENTITIES COULD DO WE THIS DATA. YOU'RE INTERACTING WITH SO AND SO AND THEY'LL HAVE YOUR DATA AND BE AWARE THEY'RE NOT CONTROLLED BY ANY OTHER PROPOSITIONS IN THE AGREEMENT WHAT THEY COULD DO WITH THE DATA. IF IT BOTHERS YOU OR YOU HAVE INTEREST IN THAT THEY CAN TALK TO THEM ABOUT IT. ETCETERA AND IT'S CONSISTENT WITH WHAT MANY OF YOU HYPOTHESIZED. >> OKAY. WE'RE NOW GOING TO TURN TO THE DOCUMENT ENTITLED AS THE RECONSENT PIECE OR RE-CONSENT DOCUMENT. I WAS NOT AT THE LAST SACHRP MEETING BUT I KNOW THERE WERE SUGGESTIONS MADE AT THAT TIME INCORPORATED AND SENT TO SUBCOMMITTEES TO ADDITIONAL FINE TUNING AND THIS NOT TRACKED BECAUSE THERE WERE FAIRLY MINIMAL CHANGES AND NOT REALLY SUBSTITUTIVE THE SUBCOMMITTEE ALL IN AGREEMENT WITH UNTIL WE GET TO THE LAST PAGES OF THE DOCUMENT. VERY LITTLE IS CHANGED FROM WHAT YOU SAW BEFORE. I THINK IT'S FAIRLY SELF-EXPLANATORY. THE QUESTION HAS COME UP ON THE ROLE OF IRBs IN ADVISING RESEARCHERS AND THE SCENARIOS IN WHICH STUDY PARTICIPANTS SHOULD BE PROVIDED WITH NEW INFORMATION AND THE WAY IN WHICH THAT MANNER SHOULD BE PROVIDED AND PART OF THE REASON THE QUESTION COMES UP IS BECAUSE THE REGULATIONS THEMSELVES ARE FAIRLY VIOLESILENT OTHER THAN THE CONSENT SHOULD NOTE THE SUBJECTS WILL BE PRESENTED WITH NEW INFORMATION THAT MAY IMPACT THEIR WILLINGNESS TO CONTINUE IN THE RESEARCH. SO I'LL WALK THROUGH THIS AND STOP ME OR START RAISING COMMENTS AT ANY POINT. FIRST PAGE GIVES THAT BACKGROUND AND TALKS ABOUT WHAT IS AND WHAT ISN'T IN THE U.S. REGULATIONS. WHEN WE GET TO PAGE TWO, LOOKING AT SOME OF WHAT WE SEE IN THE U.S. AND SOMETIMES STUDIES CHANGE AND SOMETIMES THEY'RE SIGNIFICANT AND ACROSS INTERNATIONAL GUIDELINES THERE'S NO BRIGHT LINES DRAWN ABOUT WHEN NEW INFORMATION SHOULD BE PROVIDED AND THE TERM RECONSENT DOESN'T EXIST IN THE U.S. REGULATIONS OR GUIDELINES THE EX-U.S. PERSPECTIVES IT ITH ESSENTIALLY DOES THE SAME BACKGROUND PIECE THE REGULATION DOES. AND WE GONE TO DESCRIBE THE IRB PRACTICES ON PAGE THREE AND AS YOU'LL KNOW FROM LOOKING AT THIS, THERE IS SOME COMMONALITY IN IRB PRACTICES THAT IRBs DO ROUTINELY ACCEPT REQUESTS TO APPROVE CONSENT FORMS WITH THE IDEA THERE'LL BE INSTRUCTIONS TO RECONSENT. AGAIN, IT'S NOT A REGULATORY DEFINITION OF RE-CONSENT OR CONCEPT OF RE-CONSENT AND SO THERE IS FLEXIBILITY THAT'S ALLOWED AND PROBABLY INCONSISTENCY ACROSS IRB PRACTICES BECAUSE OF THAT. AND SO ON PAGE THREE AROUND LINE 76, WE TALKED ABOUT WHAT THE DIFFERENT PATHWAYS MIGHT BE. BUT HIGHLY DEPENDENT ON THE CIRCUMSTANCES WHICH I THINK IS ONE OF THE CHALLENGES HERE. AND FURTHER COMPLICATED BECAUSE IT'S A MATTER OF LOCAL IRB PRACTICE IN THE AB SENSE OF GUIDE -- ABSENCE OF CLEAR REGULATIONS. THEN WE MOVE INTO THE SUBSTANCE OF THE DOCUMENT AT LINE 97. THE QUESTIONS FOR SACHRP TO REVIEW. AND MAKE SURE WE HAVE ANSWERS ACCEPTABLE TO SACHRP AND SHARE WITH THE REGULATED COMMUNITY. THE FIRST ONE STARTS OFF WITH A QUESTION RELATED TO TRANSITION. THERE'S FOLKS ON WHAT THE IMPLICATIONS OF THE REVISED COMMON RULE GO INTO EFFECT ON IRB PRACTICES. THIS COMPLICATES THINGS BECAUSE IRBs AND KEEP THEM ON THE OLD RULE OR TRANSITION THEM TO THE NEW RULE AND THAT HAS IMPLICATIONS FOR THINGS LIKE INFORMED CONSENT BECAUSE THE NEW RULE HAS REQUIREMENTS FOR INFORMED CONSENT THAT AREN'T IN THE IN OLD RULE. THE FIRST QUESTION IS ABOUT RESEARCHER APPROVED UNDER THE PRE-2018 RULE IS IT NECESSARY TO CONSENT TO THE REVISED RULE WHEN THE NEW INFORMATION RESULTS IN A CHANGE TO THE CONSENT DOCUMENT? HERE WE SATE THE REQUIREMENT SHOULD NOT REQUIRE A PROTOCOL TO THE REVISED RULE. JUST BECAUSE YOU'RE AMENDING THE PROTOCOL IN WAYS THAT NECESSITATE CHANGES TO THE CONSENT FORM IT DOESN'T MEAN OH, NOW WE HAVE TO TRANSITION IT. IT CAN REMAIN GRANDFATHERED. THERE'S NO REQUIREMENT TO ADD THE ADDITIONAL ELEMENTS OF CONSENT OR KEY INFORMING REQUIREMENTS TO THE -- INFORMATION REQUIREMENT VILLANO VILLANOVA EVEN WHEN IT'S GOING TO THE CONSENT DOCUMENT. QUESTIONS? THE NEXT QUESTION'S A BIT MORE BROAD. WHEN DO THE REGULATIONS REQUIRE RE-CONSENT AS NOTE BEFORE THEY DON'T. IT'S NOT A CONCEPT DEFINED IN THE REGULATIONS AND REQUIRE RESEARCHERS PROVIDE PARTICIPANTS WITH NEW FINDING IN THE COURSE OF THE WHEN THEY MAY IMPACT THE WILLINGNESS OF THE PARTICIPANT TO CONTINUE IN THE RESEARCH. UNTIL REGULATIONS ARE CLEAR THEY DON'T SUGGEST A THRESHOLD FOR THE SIGNIFICANCE OF INFORMATION OR DESCRIBE A MECHANISM FOR IMPLEMENTING THE REQUIREMENT. THE PARAGRAPH STARTING AT 116 NOTES THAT THIS IS ALL PART OF AND THERE'S STATUS OF PARTICIPANTS AT A GIVEN TIME OR FOLLOW UP IN THE SPECTRUM OF PARTICIPATION AND THE NEW INFORMATION MAY HAVE DIFFERING DEGREES OF IMPACT ON THOSE PARTICIPANTS DEPENDING WHERE THEY ARE ON THE RESEARCH. THAT CONCLUDES THAT BY PROVIDING NEW INFORMATION IT INCLUDES A RIGHT TO EXCLUDE FROM THE PARTICIPATION OR REMAIN IN THE RESEARCH. >> I WANTED TO MENTION THIS EARLY IN THE DISCUSSION AND I DON'T KNOW IF WE WANT TO PURSUE IT, I ALWAYS HAD THE IMPRESSION WHEN WE WERE TALKING ABOUT THIS THAT WE WERE TALKING ABOUT INTENTIONAL CHANGES IN THE STUDY PROCEDURES. OR A BIOMEDICAL STUDY WHERE A RISK DEVELOPS OF SOME KIND. THE ONE THAT CAME TO MIND RECENTLY IS WHAT HAPPENS IF A PROJECT HAS HAD A DATA BREACH OF SOME UNIT AND IS THERE A -- KIND AND IS THERE A DATA RISK AND SOMETHING HAPPENED THAT WASN'T INTENDED AT ALL DOES IT RAISE A QUESTION WHETHER CONFIDENTIALITY PROCEDURES ARE AS TIGHT AS THEY'RE SUPPOSED TO BE AND IS THAT SOMETHING THAT ONE MIGHT NEED TO DISCLOSE IN THIS CONTEXT. SO I JUST WANT TO RAISE IT BECAUSE IT'S NOT SOMETHING I WAS THINKING OF WHEN I READ THIS BEFORE IN ANYWAY BUT IT MAY BE SOMETHING TO THINK ABOUT INCORPORATING AS AN EXAMPLE OR AS A TYPE OF RISK THAT MIGHT BE CONSIDERED. I THINK IT'S A FAIRLY EXTREME SITUATION BUT I THINK IT COULD HAPPEN. >> IT CAN HAPPEN AND THOUGH THINGS HAVE CHANGED IT'S NOT LIMITED TO THAT. CERTAINLY NOT LIMITED TO THAT AND ON OUR LIST OF EXAMPLES THAT WILL BE IN APPENDIX ONE OR IN THE DOCUMENT ITSELF OR BOTH THERE'S NO HARM IN CALLING OUT WE'RE TALKING ABOUT CHANGES OF MULTIPLE TYPES. >> CONSUELO I'LL LET YOU GO FIRST. >> IN PROVIDING INFORMATION PROVIDES AN EXPLICIT OPPORTUNITY TO ASSERT THEIR RIGHTS. IS THERE EXISTING METHODS THAT HAVE BEEN DOCUMENTED THAT PARTICIPANTS HAVE AGREED TO -- I THINK THE WHOLE TOPIC ITSELF SEEMS TO ME AN ISSUE IN THAT PEOPLE DON'T RECOGNIZE, APPRECIATE OR KNOW HOW TO OPERATIONALIZE THE CONSENT AS AN ONGOING PROCESS. SO IF IT'S WELL ACCEPTED CONSENT IS ONGOING AND THERE'S MECHANISMS IN PLACE ALREADY THIS IS NOT CONSIDERED CONSENT. >> I DON'T KNOW A STAND ALONE THAT COVERS THAT BUT IN PREVIOUS SACHRP CONSIDERATIONS WE HAVE EMPHASIZED THE PROCESS OVER PAPER ASPECT OF IT BUT NO, I'M NOT AWARE OF GUIDANCE THAT GOES TO THE HEART OF THIS ISSUE. THAT'S PART OF THE REASONS THE QUESTIONS CAME TO SACHRP. >> I THINK THAT'S RIGHT. >> I THINK THERE'S WHY THERE'S NO RE-CONSENT IN THE REGULATIONS AND YOU RAISE AN IMPORTANT POINT THAT MAYBE WE NEED TO BE MORE EXPLICIT ABOUT WHETHER THE OPERATIONAL CONSEQUENCES OF WHAT WE MEAN AND I THINK WE GET THERE BUT IT'S DISTRIBUTED THROUGH THE DOCUMENT AND THERE'S A LATER SECTION THAT TALKS ABOUT TALKING TO PARTICIPANTS AND DOCUMENTING THEIR WILLINGNESS TO CONTINUE IN THEIR STUDY RECORD OR HAVING THEM SIGN AN ADDENDUM OR SIGN A WHOLE NEW CONSENT FORM. I THINK WE NEED TO BE MORE EXPLICIT WHAT IT MEANS WHEN WE USE THE TERMS TO MAKE IT A MORE USABLE DOCUMENT. >> I DON'T KNOW IF THAT'S A CONCEPT WE ELABORATE ON IN THE BEGINNING OF THE DOCUMET. THE PROCESS PIECES OF IT. WE MENTION IT BUT MAYBE WE'RE IN THE CLEAR ENOUGH. >> OR IF WE COVER THEM LATER PUT A PREFERENCE IN SO PEOPLE KNOW IT'S COMING. THE MORE IMMEDIATELY USABLE WE CAN MAKE THET DOCUMENT THE BETTER. -- MAKE THE DOCUMENT THE BETTER. IT'S A PRACTICAL PROBLEM. >> WE SAY SOMETHING IN LINE 139 THAT WE'RE DESCRIBING A PROCESS FOR APPROVING THE MECHANISM. WE SAY THE INFORMATION DOES NOT EXIST RIGHT NOW AND SAY THE IN INTENT OF THIS DOCUMENT IS TO EXPLICITLY PROVIDE GUIDANCE. >> I'LL REITERATE WHAT'S BEEN BROUGHT IN THE PAST I THINK IT'S IN THE UPDATED RULE AND THE IMPACT SO FROM AN IRBs POINT OF VIEW, THIS HASN'T REALLY BEEN A PROBLEM IRBs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s HAVE NOT HAD A PROBLEM DEALING WITH THIS PRACTICAL IMPLEMENTATION APPROACHES HAVE BEEN X, Y, Z SO PEOPLE KNOW WE'RE NOT START FROM SCRATCH AND THAT THE PURPOSE IS TO HELP PEOPLE THINK THROUGH IT AND MAKE IT MORE CONSISTENT. WHICH WE SAY. >> WE DO. WE TALK ABOUT THE AVAILABILITY. >> I HAVE ONE MORE COMMENT ON LINE 94 THE WORD SHOULD BE AFFECT NOT EFFECT. >> WASN'T THERE ONE MORE HAND OVER HERE? JANET? >> I BROUGHT THIS UP BEFORE AND DIDN'T SEE IT GOT ADDRESSED UP HERE. I WOULD LIKE TO SEE SOME WORDING THAT EMPHASIZES IF YOU HAVE THE ABILITY TO MAKE THIS JUST A NOTE SMEBODY SIGNS RATHER THAN STRONG GO THROUGH THE ENTIRE CONSENT DOCUMENT AGAIN, THAT WOULD BE PREFERABLE. I NOTICED IN THE MATRIX THERE'S A LOT OF OPPORTUNITIES ON THE FIRST LINE WHEN THEY SAY IT'S A MINOR CHANGE TO NOTIFY THE PERSON VERBALLY. I CAN UNDERSTAND THE NEED TO GET WRITTEN NOTIFICATION BUT I WOULD PROPOSE SAYING YOU NEED TO NOTIFY PEOPLE. SAY THERE'S BEEN A DEATH IN THE TRIAL. THAT'S IMPORTANT AND WE NEED TO KNOW THAT. YOU CAN HAVE AN ADDENDUM SAYING THEY'RE STILL WILLING TO PARTICIPATE WITHOUT SIGNING THE ENTIRE 50 PAGES. WHEN I HAVE TO SIGN AND INITIAL THE 50 MORE PAGES IT GETS LOST IT'S LIKE READING THE TERMS OF SERVICE AGREEMENT. I'D LIKE TO SEE SOMETHING THAT ADDRESSES THE IMPORTANCE AS TRYING TO MAKE THE PAPERWORK AS MINIMAL AS POSSIBLE NOT ASSUME YOU HAVE TO GO THROUGH THE FULL ENTIRE CONSENT DOCUMENT AGAIN BECAUSE THERE'S BEEN A CHANGE. >> THAT WAS THE INTENT OF THE MATRIX. >> MAYBE A LINE WOULD BE HELPFUL. >> I THINK THERE'S A COUPLE QUESTIONS THAT LEND THEM RECEIVED TO A STRONGER STATEMENT ABOUT WHAT THE OPTIONS ARE AND FOT REVIEW EVERY PAGE AGAIN. THE POTENTIAL CHALLENGE IS THERE'S A LOT OF SPONSOR WANT TO PARTICIPATE FOR CYA REASONS AND IRBs DON'T OFTEN TAKE A STAND AND SAY THAT'S TOO MUCH. WE DON'T THINK YOU SHOULD REQUIRE THIS ABOUT THE STILL CALL IT OUT IN THE DOCUMENT. THERE'S A COUPLE PLACES WHERE THERE'S AN OPPORTUNITY TO DO THAT. >> I KNOW THERE'S LOTS OF PLAYERS HERE AND THERE AND ISSUES, WE SHOULDN'T BE SHY ABOUT RECOMMENDING IT. >> THE GENERAL BACKGROUND QUESTION MAY BE BEST DIRECTED TO JERRY. IN THE CLASSICAL CLINICAL TRIAL DESIGN, ONE ASSUMES THAT RISKS AND BENEFITS AND IT'S NOT UNTIL THE LESION NEF TRIAL YOU'RE NOT ABLE TO ASCERTAIN THE NET BENEFIT OR RISK OF A TRIAL. I'M THINKING ABOUT RECENTLY THERE'S BEEN INTEREST IN ADAPTAL CLINICAL DESIGNS IN ACCELERATING THE DEVELOPMENT OF POTENTIALLY IMPORTANT PRODUCTS WHERE THERE'S UNMET NEED. IN THOSE ADAPTIVE TRIALS ALMOST BY DEFINITION THE BENEFIT RISK IS EVALUATED AND THERE'S A TIPPING POINT WHY THE TRIAL MAY PROGRESS OR A PROGRAM MAY PROGRESS INTO PHASE THREE WITHOUT THE STANDARD COMPLETION OF PHASE TWO. I'M WONDERING HOW THIS IS HANDLED FROM AN INFORMED CONSENT STANDPOINT WHERE AS PART OF THE PROGRAM OR TRIAL THERE MAY ACTUALLY BE INHERENTLY A PRE-DETERMINED TIPPING POINT. >> THAT'S A GREAT ISSUE. >> YOUR RISKS CAN BE DIFFERENT AT DIFFERENT PARTS OF THE TRIAL AND IF THEY HAVE BEEN IN A NON-TRIVIAL WAY IT WOULD PROBABLY BE APPROPRIATE IN TERMS OF DOING SOMETHING IN MAKING SURE THINGS ARE OKAY IN TERMS OF WHERE THEY'RE AT AND INTRIGUE UP THIS PARTICULAR QUESTION -- IN IN TEEING UP THIS QUESTION IT WAS TO THE REVISIONS OF THE RULES RAISING AN ISSUE THAT WASN'T AN ISSUE BEFORE AND WHEN ARE WE DOING SOMETHING UNDER THE PART OF 11 OR 116 BECAUSE THEY'RE DIFFERENT UNDER THE OLD AND NEW VERSION AND AFTER TRANSITION STUDY FROM THE OLD RULES TO THE NEW RULES DOING SOMETHING UNDER THE NEW 116 YOU HAVE TO KNOW YOU'RE DOING SOMETHING UNDER 116 OPPOSED TO OUT INFORMATION IN A WAY THAT IS SOMEHOW CATEGORIZED AS NOT RELATED TO 116. THAT'S THE SPECIFIC SCENARIO BUT YOU'RE RIGHT, THERE ARE TYPES OF STUDIES WHERE IT COULD BE APPROPRIATE TO NOT JUST VOLUNTARILY BUT YOU SHOULD BE GIVING OUT ADDITIONAL INFORMATION AND CONFIRMING A PERSON IS OKAY WHERE THEY'RE AT IN TERMS OF A PARTICULAR POSITION OR STAGE IN A CLINICAL TRIAL AND I DON'T KNOW IF THAT'S GETTING AT THAT. >> WITH A PHASE TWO, THREE ADAPTIVE DESIGN THE INDIVIDUALS THEMSELVES ARE NOT TRANSITION FROM TWO TO THREE. THEY'RE EITHER IN TWO OR THREE. I'M NOT SURE THERE'S A WHOLE LOT DIFFERENT THAN BEING IN A CLINICAL TRIAL AND THERE'S AN EVOLUTION OVER TIME. ON THE RISK SIDE THEY NEED TO BE INFORMED BUT SINCE YOU'RE NOT DOING EFFICACY ANALYSIS UNTIL A FUTURE POINT IT'S NOT CLEAR TO ME YOU WOULD THEN TELL SOMEONE UNLESS YOU TELL THEM THEY'LL KNOW SOMETHING AROUND THE EFFICACY SIDE. IT'S NOT CLEAR TO ME IT'S THE SAME ISSUE AROUND RISK INFORMATION. >> I WOULD RESPECTFULLY DISAGREE. IF YOU LOOK AT THE ADAPTIVE TRIAL AFTER THEY'VE BEEN OUT FOR A FEW YEARS, THEY CHANGE THE STANDARD OF CARE ARM FROM THE ATTACKS TO IMMUNOTHERAPY. YOU WOULD NEED TO INFORM THE PATIENTS ABOUT THE OPTIONS ASSOCIATED WITH THE NEW TRIAL. >> IF SOMETHING CHANGES IT IMPACTED ON YOU. ABSOLUTELY. I'M NOT DISAGREEING BUT SEPARATE FROM PLATFORM TRIALS LIKE LUNG MAP, IF YOU'RE DOING A SINGLE DISEASE, AN ADAPTIVE DESIGN THE PERSON THAT'S ENROLLED ON PHASE TWO DOESN'T ROLL OVER TO PHASE THREE. I'M NOT DISAGREEING WITH THE LUNG MAP. IF THERE'S AN IMPACT ON SOMETHING HAPPENING TO YOU, YOU NEED TO KNOW ABOUT THAT. >> TURNING BACK TO THE DOCUMENT. I DO HAVE -- >> I HAVE A COUPLE COMMENTS WITH RESPECT TO THE U.S. REGULATORY REQUIREMENTS. IT STARTS ON LINE 25. THESE ARE RELEVANT TO THE ISSUE OF RE-CONSENT. I'M NOTING THREE OF THESE ARE IN THE CONTEXT OF PROSPECTIVE SUBJECTS. I DON'T REALLY SEE HOW IT'S DIRECTLY RELEVANT TO RE-CONSENTING. AND SO TEEING OFF ON THAT PIECE ON THE REGULATORY REQUIREMENTS THAT'S STARTING AROUND LINE 146. I DID FIND IT INTERESTING THAT IN TERMS OF THE ACTUAL REGULATORY REQUIREMENTS, ONLY SPECIFICALLY REFERS TO SPECIFIC NEW FINDINGS. MAYBE IT'S A MATTER HOW SPECIFIC NEW FINDINGS ARE INTERPRETED. THERE'S A LOT OF ADDITIONAL INFORMATION THAT REALLY DON'T FALL AT LEAST IN MY MIND THE CATEGORY OF SIGNIFICANT NEW FINDINGS AS THEY'RE CALLED OUT ON THE APPENDIX, FOR EXAMPLE, IF YOU'RE GOING TO COLLECT NEW BIOSPECIMENS OR THERE'S A CHANGE IN THE FINANCIAL BURDEN OR SUBJECT. THAT TYPE OF THINGS AREN'T SIGNIFICANT NEW FINDINGS. THEY'RE NOT RELATED TO THE STUDY DESIGN. I'M NOT PROPOSING WE CHANGE THE REGULATIONS BUT IT JUST SEEMS THAT IT'S A PARTICULAR PROBLEM. I THINK IT'S INTERESTING IN THE REAL WORLD ALL THESE ADDITIONAL NEW INFORMATION IS BEING CALLED OUT IN SOME FASHION, SOME MECHANISM BE IT MECHANISM OR INFORMED CONSENT OR INFORMATION. I GUESS MY QUESTION IS, IS THIS MAYBE THAT SHOULD BE CALLED OUT MORE IN THIS GUIDANCE ABOUT THIS SORT OF THE GAP IN THE REGULATIONS THAT I THINK SHOULD BE REQUIRED EVEN THOUGH THEY'RE NOT. >> IN TERMS OF RECOMMENDATIONS, SACHRP CAN ALWAYS MAKE A RECOMMENDATION THE REGULATIONS ARE REVISED AND THEY WERE JUST REVISED SO MAYBE AGAIN. JUST TO TRACK BACK THROUGH SOME COMMENTS, THE REASONS WE CALLED OUT THE EXISTING REGULATIONS, IT WAS SIMPLY POINTING TO THE PROVISION OF INFORMATION. WE DID QUOTE CONSENT ON NEW PARTICIPANTS LARGLY BECAU -- LARGELY BECAUSE THERE IS NO REGULATIONS TO PROVIDE NEW INFORMATION OR WHAT THE THRESHOLD SHOULD BE AND THAT'S AT THE ROOT OF THE WHOLE DOCUMENT IS THIS IDEA THEY'RE TRYING TO FIGURE OUT HOW TO GUIDE IRBs AND RESEARCHERS IN THE ABSENCE OF A REGULATORY REQUIREMENT. AND GIVEN THERE ARE CHANGES OR NEW INFORMATION THAT WILL ARISE IN THE CONTEXT OF A RESEARCH STUDY WHILE THERE MAY NOT BE A SIGNIFICANT RISK CHANGE OR IN THE STUDY DESIGN NEVERTHELESS HAVE AN IMPACT ON PARTICIPANTS THEY SHOULD BE MADE AWARE OF BECAUSE IT COULD IMPACT THEIR PARTICIPATION IN THE STUDY AND THE ONES AROUND LINE 25, THEY'RE THERE BECAUSE THAT'S ALL THE REGULATIONS SAY AND IT'S MAKING THE POINT THE REGULATIONS DON'T REALLY HAVE ANY SUBSTANCE IN THIS CONTEXT OF RE-CONSENT OTHER THAN CALLING OUT IN THE CONSENT THAT ADDITIONAL ELEMENTS WHEN APPROPRIATE THOUGH SOME IRBs HAVE IT IN THEIR GENERAL CONSENT AND SIGNIFICANT NEW FINDINGS DEVELOP MAY BE GIVEN TO SUBJECTS THAT MIGHT RELATE TO THEIR WILLINGNESS TO CONTINUE. SIGNIFICANT NEW FINDINGS NOT OTHER WISE DEFINED. IT SOUNDS LIKE A SIGNIFICANT NEW THING. THE WORLD OF WHAT MIGHT IMPACT A pTHAN JUST THAT.T IS GREATER >> IN THE IRB WE DEAL WITH THIS ALL THE TIME WHILE THERE'S NO SPECIFIC CALL OUT IT'S NEVER STOPPED OUT FROM ACQUIRING CONSENT. I'M IN FAVOR OF THINGS BEING FLEXIBLE. I THINK IRBs ALREADY CONSIDER THEMSELVES REGULATORY COMPLIANCE BODIES AND THEY SHOULD BE THINKING MORE BROADLY BUT IT'S AN AREA WHERE A CHANGE COMES THROUGH IT ADDS TO COLLECTIONS AND WHEN SOMETHING CHANGES IT ADDS TO AN AMENDMENT AND THE IRB DEBATES WHERE THE CONSENT FORM NEEDS TO BE CHANGED AND ALL THE THINGS WE'VE DISCUSSED. >> SURE. AND THEY'RE DEALING WITH THE IRB LEVEL ON A REGULAR BASIS. WE RECEIVED NEW INFORMATION AND THINGS LIKE A DATA BREACH OR A LOST LAPTOP WHERE THAT'S NEW INFORMATION AND WE WANT TO PROVIDE IT TO PEOPLE. I DON'T KNOW IF YOU CALL IT RE-CONSENT BUT WE'RE GIVING THEM NEW INFORMATION AND IT MAY CAUSE THEM TO WITHDRAW THEIR CONSENT. WE RECEIVE LOTS OF AMENDMENTS THAT HAVE A LITANY OF MINOR CHANGES BUT IN THE END WE SAY WHEN THEY COME IN RE-CONSENT THEM BECAUSE YOU CHANGED THINGS IN THE DOCUMENT AND THE DOCUMENTER ED RE-CONSENT AND THE IRB APPROVES THAT AND GOES FORWARD. THERE'S A LOT OF FLEXIBILITY. I DON'T KNOW IRBs ALWAYS EXERCISE IT AND WE CAN ENCOURAGE THAT MORE IN THE DOCUMENT. >> I'M NOT SUGGESTING EVERY LOST LAPTOP HAS TO BE REPORTED TO EVERY PARTICIPANT. WHEN YOU IDENTIFY THAT PROCEDURE SYSTEMATICALLY NOT BEING FOLLOWED PROPERLY THERE'S A RISK YOU CAN CONSIDER. >> WITH THAT CONVERSATION IN MIND LET'S KEEP GOING THROUGH THIS. I HAVE NOTES ABOUT BEING MORE CLEAR ABOUT CALLING OUT PROCESS AT MULTIPLE OPPORTUNITIES IN THE DOCUMENT. WE WERE GETTING INTO THE 108 QUESTION ABOUT RE-CONSENT AND THEY DON'T REALLY. IT TALKS ABOUT PROVIDING NEW INFORMATION AND THAT THERE'LL BE FACTORS THAT INFLUENCE WHETHER OR NOT THAT NEW INFORMATION IS RELEVANT TO GIVEN PARTICIPANTS. I THINK IT'S ONE OF THE CHALLENGES FOR THE TOPIC OVERALL. THE FINAL QUESTION ASKS TO THE REGULATORY CONCEPT OF RE-CONSENT AND IF SOMETHING SHOULD BE RECOMMENDED. IT'S THE PLACE WHERE THERE'S CONSENSUS TO THE COMMITTEE WHERE WE MORE ADVOCATE FOR THAT SORT OF REGULATORY CHANGE AND THIS IS THE POINT TO DO IT BECAUSE WE ONLY HAVE THE 116C5 FINDINGS THAT MAY IMPACT WILLINGNESS. THAT'S WHAT THE FIRST PARAGRAPH TALKS ABOUT. THE SECOND PARAGRAPH INDICATES HAVING GUIDANCE IN THIS AREA MAY BE MORE HELPFUL THAT'S NOT AS STRONG AS SAYING REGULATIONS MAY HAVE A GREATER IMPACT BUT I DON'T KNOW HOW THE ENTIRE COMMITTEE FEELS ABOUT THAT. >> I AGREE WITH GUIDANCE. I THINK PART OF IT COMES DOWN TO THE INTERPRETATION OF FINDING THAT DOESN'T CONSTRICT IT TO A RESULT OF THE RESEARCH TO ANYTHING THAT WOULD IMPACT ON THE WILLINGNESS TO PARTICIPATE. EVEN IF YOU TRIED TO WRITE A REGULATION YOU'D END UP STUCK USING A WORD THAT COULD END UP BEING CRITICIZED FOR THE SAME LIMITATION BUT IN A DIFFERENT WAY. IT WOULD TAKE FOREVER TO DO THAT. GUIDANCE TAKES TIME AS WELL. A REGULATION CHANGE WOULD LIKELY FOUNDER AND A NUMBER. I THINK THE GUIDANCE APPROACH IS REASONABLE. I WONDER WHETHER ANYBODY FEELS DIFFERENTLY. >> I AGREE WITH YOU IN TAKING THE GUIDANCE APPROACH. I WONDER IF WE SHOULD OR SHOULDN'T INVOKE THE MATERIAL TO THE PARTICIPATION DECISION IDEA. THAT'S WHAT COMES UP IN OTHER CONTEXTS IN A PHAGE -- FAMILIAR IDEA. IT'S A WORDING PEOPLE ARE A BIT USED TO THAT CONSENT SHOULD INCLUDE THE ELEMENTS MATERIAL TO A PARTICIPATION DECISION. >> I'M SUPPORTIVE OF THE GUIDANCE APPROACH BECAUSE IT PROVIDES AN OPPORTUNITY TO BE A BIT MORE CONTEXTUAL AND LESS PRESCRIPTIVE. >> THE NEXT QUESTION MAY LEND ITSELF TO YOUR QUESTION WHEN AN IRB WE CONSENT AS ADVISABLE OR AN ETHICALLY APPROPRIATE THING TO DO, AND HERE WE TOUCH ON THE APPENDIX ONE AND TWO AND WE CAN TURN TO THOSE AFTER WE GET THROUGH THE DOCUMENT BUT PUTTING A CLEAR FRAMEWORK AROUND THIS PROVED CHALLENGING TO THE SUBCOMMITTEES. WE CALL OUT THE FACT THAT IT'S PRETTY CLEAR WHEN THERE'S NEW OR INCREASED RISK TO PEOPLE OR MODIFICATIONS THAT INCREAS BURDENS ON PARTICIPATION. WHEN WE STEPPED AWAY FROM THAT TO OTHER EXAMPLES WE GOT IN DISCUSSIONS WHERE SOMETHING WAS PERCEIVED IMPORTANT TO ONE PERSON AND NOT THE OTHER AND CHA WHOO ARE THE THRESHOLDS TO FIGURE OUT WHAT ARE GENERALLY ACCEPTED OR AGREED UPON SITUATION THAT WOULD LEND ITSELF TO AN IRB TAKE STANCE THAT RE-CONSENT IS APPROPRIATE AND SHOULD BE DONE. >> CHECK ME ON THIS BUT THE PARAGRAPHS SEEM TO OMIT ONE OF THE MOST GLARING EXAMPLES WE'RE ALL FAMILIAR WITH THE TUSKEGEE STUDY WHERE A NEW MODALITY OF TREATMENT HAS EMERGED THAT MAKES THE STUDY PARTICIPANTS SHOULD AVAIL THEMSELVES OF. I THINK WE OUGHT TO INCLUDE THAT ONE. >> SO THAT DOES END UP APPEARING IN THE APPENDIX. >> I DON'T THINK IT'S A PROBLEM. THERE'S NOT CONCERNS OF HOW WE'RE DOING IT NOW AND DIDN'T HAVE CONCERNS ABSENT THE COMMON RULE AND IN THE IRB WORLD AND EVERYTHING IS A STRONG ARGUMENT FOR CONSISTENCY FOR US TO THINK ABOUT THIS BUT I DON'T THINK THE COMMITTEE SHOULD BE CONCERNED WE'RE RESPONDING TO A NEED THAT ARISES BECAUSE WE'RE NOT ASKING PEOPLE TO REAFFIRM THEIR PARTICIPATION. >> WE TRIED TO NOT TO BOG THE DOCUMENT DOWN BECAUSE IT PROVED A CHALLENGE BUT WE COVERED THAT SCENARIO IN THE APPENDIX. >> I TLIRNG IT'S FINE TO REFER -- >> I THINK IT'S FINE TO REFER TO A REASONABLE PERSON OR PARTICIPANTS OR SOMETHING I'M RIGHT-HANDED OF THE COMPLEXITIES OF CONSENT LAWS AND JERRY KNOWS MORE ABOUT THIS THAN OTHERS BUT WHERE THE OBLIGATION OF INFORMED CONSENT IS NOT TO TELL SOMEONE WHAT THEY SPECIFICALLY WANT TO KNOW BECAUSE THERE'S NO WAY TO KNOW THAT MY OBLIGATION IS TO TELL THEM WHAT A REASONABLE PATIENT WOULD WANT TO KNOW. THAT'S TRUE IN THE STATE OF PENNSYLVANIA. IT'S TRUE IN MOST STATES IT'S THE STANDARD. AND HERE THE IRB FUNCTIONS LIKE A PROXY FOR REASONABLE PARTICIPANT AND THE CONVERSATION THAT WOULD TAKE PLACE AROUND WHETHER THAT SHOULD BE DISCLOSED. I'M FINE WITH THE LANGUAGE THAT LEPT OUT OF ME AND THINK ABOUT THAT IN THE CLINICAL SETTING. YOU HAVE IT CONSIDERED AS REASONABLE BY PERSON THERE. THE STANDARD CAN'T BE WHAT ANY ONE INDIVIDUAL PERSON MAY WANT TO KNOW. >> WHAT'S IMPORTANT HERE IS WE'RE RESPONDING TO WHAT JANET SAID WHICH IS THE EVER SINGLE TIME THERE'S A MUNE OUT CHANGE AND -- MINUTE CHANGE AND I THINK THE DOCUMENT DOES A GOOD JOB OF MAKING THE POINT WE SHOULD BE THINKING NOT ABOUT THAT BUT WHAT PEOPLE NEED UNDER THOSE CIRCUMSTANCES AND NOT BE SO CONCERNED. WE'RE REACTING TO PEOPLE OVER REQUIRING STUFF AND IN THINKING ABOUT WHEN IT SHOULD BE. THERE MAY BE A COUPLE PLACES WRAPS AT THE VERY BEGINNING WHERE WE MIGHT EMPHASIZE MORE IT MAY BE THE CONSENT FORM RATHER THAN THE PROCESS THAT'S THE ISSUE TO NOT DISCOURAGE PEOPLE FROM DISCLOSING MORE INFORMATION THAN THE REGULATIONS MAY REQUIRE. OVERALL IT DOES A GOOD JOB OF SERVING THAT PURPOSE AND BE REASSURING WITHOUT SAYING DON'T PROVIDE INFORMATION TO PARTICIPANTS WHEN THERE'S SOMETHING THEY MAY BE INTERESTED TO KNOW BUT NOT BURDEN THEM AT THE SAME TIME WITH THAT INFORMATION. >> I HAVE A FUNDAMENTAL PROBLEM WITH REASONABLE PERSON. SOMETIMES IT'S NOT REALLY CONSIDERING THAT PEOPLE FROM BACKGROUNDS OR COMMUNITIES HAVE EXPERIENCED EXCESS HARM FROM RESEARCH WILL HAVE HEIGHTENED CONCERNS AND A DIFFERENT THRESHOLD OF CONCERNS AND DISTRUST WITH THE PROCESS. AND SOMETIMES IT'S DEEMED OUTSIDE OF WHAT A REASONABLE PERSON WOULD CONSIDER AN ISSUE. THE IDEA AND REASONABLE PERSON IS APPROPRIATE AS SOME CONTEXT NOT TO RESPOND TO EVERY SINGLE CONCERN THAT MIGHT BE REALLY FAR MY EXPERIENCE IS SOME PEOPLE'S WHOSE CONCERN IS VALID ARE PUT IN THE CATEGORY OF NOT BEING REASONABLE. JUST BEING CONSCIOUS OF WHAT AND WHO DEFINES REASONABLE AND HOW THAT'S ACTUALLY -- >> BEFORE SKIP RESPONDS, THAT MAY BE A FOOT NOTE TO A REASONABLE PERSON BECAUSE IT MAY BE HARD TO OTHERWISE CONTEXTUALIZE IN THE FOOT NOTE ESPECIALLY IF SOMEBODY HELPS ME WRITE IT. >> I WANT TO REMIND US AND THEY'RE GREAT POINTS AND THAT'S SOMETHING WE DISCUSSED AND SHOULD DISCUSS AGAIN MY TAKE ON WHAT THE DOCUMENT SHOULD DO IS LITERALLY ABOUT THE CONSENT FORM AND WE GIVE A LOT OF BACKGROUND AND THAT'S WHAT WE'RE GETTING INTO HERE AND NOT TO SAY WHAT WE DO IS RIGHT. BUT MY UNDERSTANDING WAS IT'S THE USE OF THE FORM AND MODIFICATIONS AND WHETHER THERE'S ALTERNATIVES TO THAT BECAUSE IF YOU HAVE STUDY APPROVED UNDER THE NEW RULE, SAY RECRUITMENT IS OVER OR ONGOING, AND YOU CREATE A NEW FORUM, IF YU CREATE A NEW FORUM FOR A CHANGE IT HAS TO MEET THE FULL NEW REQUIRED ELEMENT AND FORMAT OF CONSENTING WHERE THERE'S ALTERNATIVES THAT DON'T REQUIRE YOU TO DO THAT AND I THINK PART OF THE WORK WE WERE TRYING TO DO WAS TO GET PEOPLE TO THINK ABOUT THAT BEFORE THEY EMBARK ON HUGE PURPOSES TO THE CONSENT AND MAY CONFUSE THE PARTICIPANTS AND IF ENROLLMENT IS ONGOING AND HALF THE SUBJECTS HAVE KIND CONSENT WE WANT TO DISCOURAGE WHERE YOU PUT INFORMATION IN THE NEW UPDATED RULE CONSENT AND THEN MAKE EVERYBODY SIGN THAT IN THE PAST THERE'S GOING TO BE PUSH BACK BECAUSE PEOPLE DON'T WANT TO VERSIONS OF THE CONSENT BUT FROM A CLARITY POINT OF VIEW IT'S CONFUSING TO HAVE A MINOR CHANGE AND GIVEN A DOCUMENT THAT'S DIFFERENT AND REFORMATTED. TO ME, THIS WAS NOT SO MUCH ABOUT THE FUNDAMENTALS OF CONSENT AND WHERE TO MAKE IT BETTER AND THE TOOLS WE HAD WHERE SOMETHING HAD TO BE COMMUNICATED TO PARTS PANTS. >> AGAIN, I THINK THE STARTING POINT WAS TRYING TO CATEGORIZE INSTANCES YOU'RE GIVING SOMEBODY ON THE SIDE OF RE-CONSENTING OR NOT RECONSENTING BECAUSE IF IT'S ON THE RE-CONSENTING SIDE, THAT DOES HAVE SOME CONSEQUENCE AND HOW IT HAD TO BE CATEGORIZED AND THERE'S A BETTER ARGUMENT YOU DON'T HAVE TO WORRY ABOUT WHAT THE NEW RESIZED RESOLUTIONS SAY ABOUT WHEN YOU OBTAIN INFORMING BECAUSE YOU'RE NOT OBTAINING INFORMING -- INFORMED CONSENT AT THAT POINT. IT RAISES SOMETHING WE NEED TO BE CLEAR ABOUT WHEN WE USE THE LANGUAGE AND WE'RE BACK AND FORTH. WE AFFIRM YOUR WILLINGNESS TO PARTICIPATE AND WE NEED TO BE CLEAR WHEN WE SAY RE-CONSENT IN THE WAY YOU MEAN IT, IT'S RESIGNING AN INFORMED CONSENT UNDER THE REGULATION BECAUSE BECAUSE IT MAY MEAN REAFFIRMING YOUR WILLINGNESS TO PARTICIPATE. AND YOUR QUESTIONS DO THAT IN THE 144 VERSUS 158. AND THE CONSENT FORM AND ETCETERA, THE FACT OF HOW YOU'RE DOING IT WHETHER YOU'RE GIVING THE PERSON THE WHOLE CONSENT FORM MAY IN FACT ALTER HOW YOU CATEGORIZE WHAT THE EVENT IS AND THAT'S PERFECTLY REASONABLE TO THINK ABOUT BUT THE BROADER QUESTION IS WHAT THINGS ARE IN THE RE-CONSENT POT AND WHAT THINGS ARE IN THE NOT RE-CONSENT POT BECAUSE THE LINES YOU DRAW THERE MAY ON OUR END FORCE US TO GO IN ONE DIRECTION OR ANOTHER IN TERMS OF WHEN YOU ARE NOW REQUIRED TO DO SOMETHING THAT THE REVISED REGULATIONS SAY IN TERMS OF OH, SINCE YOU'RE NOW CONSENTING SOMEBODY AS A RE-CONSENT AND UNDER THE NEW REGULATIONS DUE TO OTHER CIRCUMSTANCES, YOU HAVE TO USE A CONSENT FORM THAT MEETS THE STANDARDS OF HAVING THE INFORMATION SECTION ETCETERA. >> SO NOW I HAVE TWO COMMENTS. ONE IS ON THE ONE HAND, 116C5 BASICALLY SEEMS TO TAKE AN OPT-OUT POSITION WHERE SIGNIFICANT NEW FINDINGS THAT AAFFECT YOUR ABILITY TO CONTINUE. PROVIDE THE INFORMATION AND WHAT WE'RE TALKING ABOUT ARE DIFFERENT WAYS OF PROVIDING INFORMATION REGARDED AS DIFFERENT LEVEL OF SIGNIFICANCE. IF YOU'RE NOT WILLING TO CONTINUAL SAY NO THANKS NOW. RE-CONSENT IS AN OPT-IN. IF RE-CONSENT MEANS DIFFERENT BURDENS WITH RESPECT TO CONFORMING TO THE RULE OR REVISIONS MAYBE IT WOULD MAKE SOME FOLKS WHO SAY WE NEED A NEW CONSENT FORM THINK DIFFERENTLY BUT THERE'S ALWAYS ADDITION IMPLIED BY THE PARTICIPANT WHETHER I'LL CONTINUE OR NOT AND MAYBE WE CAN MAKE THAT CLEARER WITH THE OKAY, THIS DOESN'T RISE TO THE LEVEL OF RE-CONSENT BUT WE WANT TO PROVIDE INFORMATION AND STILL EXPECT THE PERSON TO MAKE A DECISION TO CONTINUE OR NOT CONTINUE BASED ON THAT. THAT'S IN RESPONSE TO WHAT STEVEN AND JERRY WERE SAYING. WITH RESPECT TO CONSUELO'S POINT, NOW THAT WE HAVE THE LANGUAGE OF THE REASONABLE PERSON IN THE REVIVED COMMON RULE -- REVISED COMMON RULE, IT'S ABSOLUTELY ESSENTIAL FOR US EVERY TIME THE TERM COMES UP WE ADD WHAT'S IMPLIED THE REASONABLE PERSON UNDER ALL THE CIRCUMSTANCES BECAUSE THE POINT OF USING A TERM LIKE REASONABLE PERSON IS NOT EVER TO SAY THAT THERE ARE SOME PEOPLE WHO ARE UNREASONABLE BUT TO SAY THAT THE CONCERNS THAT PEOPLE WHO ARE IN A MINORITY HAVE ARE REASONABLE BECAUSE OF THEIR CIRCUMSTANCES. I THINK IF WE CAN BRING THAT LESSON HOME THEN PEOPLE WILL UNDERSTAND WHAT THE LAWYERLY USE OF REASONABLE PERSON IS INTENDED TO MEAN AND WE HAVE TO HELP PEOPLE UNDERSTAND THE INFORMATION BY TAKING ACCOUNT OF ALL THEIR CIRCUMSTANCES AND WHY THEY MAKE THE CHOICES THAT THEY DO. I WOULD ARGUE FOR ADDING UNDER ALL THE CIRCUMSTANCES ANY PLACE REASONABLE PERSON APERIODS IN THE DOCUMENT AS A START BUT WE SHOULD DO THAT GOING FORWARD. >> I AGREE AND NANCY'S A LAWYER. I DON'T THINK IT'S JUST ABOUT THE LANGUAGE BUT THE CONCEPT OF CONCEPT AND MEANT TO CONTEXTUALIZE THE BROADER CONTEXT. I DON'T THINK WE CAN GET AWAY FROM STRUGGLING WITH SOME OF THE LANGUAGE SUCH AS REASONABLE PERSON AND I AGREE WITH YOUR POINT ABOUT THE FACT THAT AND I'LL USE MAYBE A RATHER CRUDE EXAMPLE. IF IT WAS A STUDY IN SICKLE CELL AN ALL-WHITE IRB, THERE'S A PROBLEM WITH THAT JUST ON THE OPTICS IN TERM OF A REASONABLE PERSON. IT DOESN'T WORK FOR ME. WHETHER YOU ADD THE LEGAL TERM WHETHER IT HELPS OR REASONABLE PERSON IN THE CONTEXT OF THE RESEARCH STUDY OR SOMETHING, I WOULD HOPE WE COULD PLODFY THAT TO -- MODIFY THAT TO ADDRESS THE CONCERN HOW REASONABLE PERSON IS INTERPRETED. >> JOANNE AND SANDY. >> ARE WE DONE WITH THE REASONABLE PERSON DISCUSSION IN UNDER PARAGRAPH 154 THE IRB MAY CONSIDER THE STATUS OF THIS STUDY AND TAKING INTO ACCOUNT THE STUDY STATUS AND ALL THAT. MA WE'VE SEEN AND MAYBE -- WHAT WE'VE SEEN AND MAYBE IT'S UNIQUE TO FDA THE SPONSORS ALSO WANT TO BE ENGAGED IN THE DISCUSSION. WE'VE HAD IRBs SAY IT RISES TO THE LEVEL WHERE YOU SHOULD GO BACK TO THE PATIENT AND THE SPONSOR OF THE CI IS SAYING NOT NECESSARILY. I THINK IT WOULD BE HELPFUL TO MODEFY THAT THAT THE IRB SHOULD CONSIDER WHAT THE SPONSOR AND INVESTIGATOR ARE THINKING SINCE THEY DRAFT THE INFORMED CONSENT. I DON'T THINK WE'D GIVE THEM THE VETO POWER BUT TO TAKE INTO ACCOUNT WHAT THEY'RE THINKING AND WHERE THEY'RE COMING FROM. >> I AGREE. I'M NOT SURE IF THAT'S THE RIGHT SENTENCE TO PUT IT INTO. THAT'S THE STATUS OF THE PARTICIPANTS. >> I THINK THERE'S OTHER THINGS TO FACTOR IN. >> THE INVESTIGATOR SHOULD BE P PROPOSING WHAT THAT OUGHT TO BE. THE IRB IS THEN CONSIDERING THAT PROPOSAL SO THAT KOUD BE ADDED. I'M AT ODDS WITH EVERY WHICH IS PROBLEMATIC. I REELS MY IRB EXPERIENCE AND YOU'VE SEEN ONE AND THE WHOLE THING. IT SEEMS WE ROUTINELY DID THIS AND I'M CONCERNED ABOUT IRB'S THAT ROUTINELY TELL THEM WHAT TO DO. THE DEFAULT IS THEY WANT TO MAKE SURE IT'S JUSTIFIED IF THE ADDENDUM HAS TO BE PREPARED AND THE INVESTIGATOR IS THE SAME. I'M CONCERNED ABOUT US POSING THINGS THAT SOUND LIKE PROBLEMS THAT ARE NOT THERE. [ [NO AUDIO] >> SO I DON'T KNOW WITH JOANNE'S COMMENT IF WE WANT TO SAY SOMETHING ABOUT THE ROLFE SPONSORS -- THE ROLE OF SPONSORS AND WHO OTHERS THAT ARE ABSENT THAT ARE ROUTINELY PRESENT AND SHOULD BE CONSIDERED WE OMITTED. SOME WORK WITH PATIENT ADVISORY COMMITTEES TO HELP WITH THE DESIGN OF THE STUDY AND PRESUMABLY THE CONSENT FORM. >> IRB'S SHOULDING -- SHOULD BE DOING THAT AND THIS IS RELATED TO THE STATUS OF THE STUDY. IT'S VERY NARROW. IT'S NOT PARTICIPANTS' CONCERNED BUT THE STATUS WHETHER IT'S ENROLLING OR NOT ENROLLING AND IT MAY HAVE DIFFERENT IMPLICATIONS AND THINK WE SHOULD BE FOCUS OND WHAT -- FOCUSSED ON WHAT WE WERE ASKED TO ADDRESS. >> IF WE HAVE AN OPPORTUNITY SOMEWHERE ELSE IN THE DOCUMENT WHERE IT MAKES MORE SENSE WE CAN WEAVE IT IN. >> THEY WERE INCONSISTENT AND THINGS USED. >> I CAN'T RECALL BUT I DON'T BELIEVE -- I DON'T KNOW WE'VE TALKED IN THE BEGINNING OF THE DOCUMENT ABOUT SOURCES OF NEW INFORMATION AND IF WE HAVEN'T, WE CAN ACKNOWLEDGE THEY COME FROM PLACES LIKE THE INVESTIGATORS OR THE SPONSORS OR THE REGULATORS SOMETIMES. SKIP. >> SCROLL UP TO 137. YOU'VE GOT THIS PHRASE THAT SAYS GUIDANCE FOR SPONSORS AND RESEARCH AND A CONSISTENT APPROACH. YOU COULD INSERT SOMETHING THERE ABOUT THE COMMUNICATION PROCESS THE PROPOSALS, THE PATIENT COMMUNITY AND CONTEXT. IF YOU WANTED TO ADD A SENTENCE THAT BUILDS ON SPONSORS RESEARCHERS AND IRBs, THAT COULD BE A PLACE TO JUST PUT IT TO SAY WE KNOW THIS IS A MORE COMPLEX QUESTION. THE IRB NEEDS TO DO CERTAIN THINGS BUT THERE'S OTHER STUFF GOING ON BEHIND THE SCENES WITHOUT GETTING INTO TOO MUCH DETAIL. >> I THINK THAT'S A GREAT SENTENCE AND COULD BE PUT UP FRONT IN THE DOCUMENT. IT WOULDN'T HURT TO REPEAT IT. I THINK IT CAPTURES THE PURPOSE OF THE DOCUMENT WELL. >> OKAY. >> SO THE NEXT QUESTION START AT 158 GETS TO THE PROCESS PIECE OF IT AND WHAT THESE HOW INFORMATION IS PROEFRDED AND THE QUESTION -- PROVIDED AND WHEN IT APPROPRIATE TO PROVIDE INDIVIDUAL THE APPROPRIATE INFORMING BUT NOT OBTAIN CONSENT AGAIN AND DIFFERENTIATE BETWEEN CONSENT WITH A NEW FORM AND DOCUMENTATION AND THE WHOLE PROCESS VERSUS PER -- PERTINENT INFORMATION THAT MAY IMPACT THE SUBJECT. >> AND LINES 171 TO 173 MAYBE ADDRESS YOUR COMMENT, JANET, ABOUT THE BURDEN ON THE PARTICIPANT. >> THE GOAL OF THE ANSWER WAS TO BE CLEAR IRBs HAVE FLEXIBILITY AND THEY SHOULD BE JUDICIOUS IN HOW TO PRESENT THAT AND NOT DEFAULT TO A RE-CONSENT AND IF IT CAN BE PRESENTED THROUGH AN ADDENDUM OR ANOTHER RE-CONSENT MECHANISM, THAT'S OKAY. >> I THINK MAYBE NANCY'S APPROACH OF OPT-IN AND OPT-OUT WE NEED TO BE CLEAR WHEN WE SAY RE-CONSENT WE MEAN REGULATORY CONSENT BECAUSE THERE'S A COMMON SENSE USE OF THAT TERM IS NOT GOING TO BE UNDERSTOOD THAT WAY UNLESS WE'RE VERY EXPLICIT. >> IN THE BEGINNING OF THE DOCUMENT WE HAVE TO BE VERY CLEAR ABOUT THAT. >> THE SIG TOUR LINE. -- SIGNATURE LINE. >> IT'S NOT RE-CONSENT BY THE REGULATIONS. IT'S JUST DOCUMENTED REAFFIRMATION OF YOUR WILLINGNESS TO PARTICIPATE. I WISH WE HAD OTHER WORDS FOR THIS BECAUSE I THINK EVERYBODY GETS CONFUSED. >> I DON'T WANT TO GET INTO DEVICE REGULATIONS BUT LEAST BURDENSOME. JUST A THOUGHT. I DON'T FEEL STRONGLY ABOUT IT BUT UNOBTRUSIVE DIDN'T FIT FOR ME. DEVICE SPEAK. BUT IF JOANNE'S OKAY WITH THAT, WE CAN GO THERE. >> I THINK THERE'S A COUPLE SITUATIONS WE MAY OR MAY NOT WANT TO CALL OUT HERE. ONE I MENTIONED ALREADY WHICH IS DURING A STUDY THAT'S ONGOING OR YOU FIND THAT THERE HAS BEEN SOME SIGNIFICANT FAILURE OF THE PROTOCOL THAT HAS SYSTEMATICALLY COMPROMISED CONFIDENTIALITY. ANOTHER POSSIBILITY THAT COULD OCCUR EITHER DURING THE STUDY OR AFTER THE STUDY IS OVER IS A DATA BREACH THAT HAS SIGNIFICANTLY COMPROMISED THEIR DATA. NOW, IN SOME CASES IF YOU SAY YOU HAVE A SOCIAL SECURITY NUMBER THIS MAY BE A DATA BREACH WHERE YOU HAVE LEGAL OBLIGATIONS TO REPORT BUT EVEN ONE THAT DOES NOT INCLUDE THAT MIGHT BE SOMETHING YOU NEED TO REPORT. IF IT'S LIKE UCLA AND THEY'VE BLOWN THE WHOLE DATA SYSTEM THEY'LL GET REPORTED ANYWAY BUT IF IT'S A STUDY SPECIFIC DATABASE THAT WAS BREACHED IT MAY BE SOMETHING YOU NEED TO REPORT. IT'S NOT A RE-CONSENT ISSUE BUT CERTAINLY A RECONTACT AND INFORM ISSUE. >> OTHER QUESTIONS OR COMMENTS ON THIS SECTION? >> IT SEEMS LIKE IT MAY BE WORTHWHILE TO TAKE THE APPROACH TO THE LAST DOCUMENT AND HAVE SOME PRINCIPLES STATED UP FRONT. GENERAL PRINCIPLES LIKE NANCY'S COMMENTS AND LEAST BURDENSOME METHODS FOR ETCETERA AND HAVE THEM BROKEN OUT RATHER THAN BY INDIVIDUAL QUESTIONS. >> I THINK WE CAN LOOK AT THOSE. >> OTHER COMMENTS ON THIS SECTION? ALL RIGHT. THE LAST SECTION ARE SOME ADDITIONAL QUESTIONS THAT THE SUBCOMMITTEE MEMBERS THOUGHT WERE IMPORTANT TO PROVIDE ANSWERS TO IN THIS DOCUMENT. ONE IS THE ACT OF TRANSITIONING REQUIRE RE-CONSENT AND IN SHORT WE SAY NO. AND SOME FELT WHILE THERE'S NO REGULATORY REQUIREMENT THE IRB HAS THE DIRECTION TO DECIDE WHEN -- DISCRETION TO DECIDE WHEN THERE'S DISCLOSURES NOT ON THE COMMON RULE MAY BE REVISED. WHEN THERE'S A CONSENT FORM THAT DOESN'T TALK ABOUT SECONDARY USE IN THE WAY THE NEW CONSENT REQUIREMENTS WOULD MAKE NECESSARY THE IRB COULD CERTAINLY DECIDE THAT'S NEW INFORMATION TO PROVIDE. WHETHER IT'S THROUGH A RE RE-CONSENT PROCESS AND WE SPLIT OFF AN ADDITIONAL QUESTION RELATED TO THAT, CAN THE IRB DECIDE PRE-ENROLLED PARTICIPANTS NEED TO BE PROVIDED WITH ADDITIONAL INFORMATION AND IF SO WHAT THE MECHANISM FOR DOING THAT WOULD LOOK LIKE. AS I LOOK AT THE RE-CONSENT AND BUNS -- ONCE WE HAVE A BETTER DEFINITION OF RE-CONSENT IT WILL STRENGTHEN THE WHOLE DOCUMENT. THAT'S WHAT WE HAVE THERE. I'M LOOKING AT THE CLOCK AND I HAVEN'T TOUCHED ON APPENDIX ONE OR TWO YET. >> I THINK WE SHOULD WRAP THIS UP. WE'RE OBVIOUSLY GOING TO SEE IT AGAIN. EVERYBODY'S FLIGHTS HAVE BEEN CANCELED BECAUSE OF THE NOR'EASTER SO WE CAN STAY HERE ALL AFTERNOON. NO, LET'S USE ANOTHER FIVE MINUTES AND WRAP IT UP AND BRING OUR LUNCHES BACK BECAUSE I THINK THE TOPICS THAT ARE REMAINING ARE SIGNIFICANT. >> IT STARTED ALREADY. >> AT THE BEGINNING OF THE DOCUMENT I THINK WE'LL BE DOING THIS FOR THE OPT IN AND OPT OUT AND ONE MINOR WORDING THING AND MAYBE PEOPLE FEEL DIFFERENTLY BUT ON LINE 13, EXTENDED CONSENT PROCESS DIDN'T QUITE CAPTURE IT FOR ME. TO ME EXTENDED SOUNDS LIKE GIVING THE CONSENT FORM TO A POTENTIAL PARTICIPANT SAYING GO HOME AND THINK ABOUT IT AND SO ON AND SO FORTH. AND THE CONSENT HAS BEEN EXTENDED OVER A NUMBER OF DAYS. THE WORD ONGOING MAY BE BETTER. THIS IS WHERE I THINK MAYBE YOU WANT TO BREAK THE PARAGRAPH AND WHERE A DISCUSSION OF THE COMPLEXITIES OF WHAT'S OPT-IN AND OPT-OUT AND RE-CONSENT AND CONSENT CAN GO HERE. >> THANKS, SKIP. >> I'LL JUST ASK ONE THING BECAUSE I ACTUALLY DON'T LIKE THIS AND WE'VE HAD THE REQUIREMENTS FOR DECADE. WE THOUGHT THEY WERE ETHICAL. THERE'S THINGS WE CAN DO BETTER WITH CONSENT BUT IT DOESN'T SEEM LIKE WE SHOULD CONSIDER THAT NOW THAT WE HAVE KEY INFORMATION AND DISCLOSURE OF OTHER USES, ALL THE STUFF ADDED. I THINK THERE'LL BE TROUBLE IF THEY THINK THEY NEED TO WRITE IT TO MEET NEW REQUIREMENTS WHEN WE FOUND THEM ETHICAL BEFORE. >> OKAY. >> I WANT EVERYBODY TO KNOW IN MY NOTES FOR THE MEETING I WROTE LOOKS GOOD AND SUBSEQUENTLY WROTE I WAS WRONG. WHY DON'T WE TRY TO GET OUR LUNCHES AND BE BACK AT 12:30 AND WE CAN JUMP INTO TRY TO DO -- WELL, I'LL THINK ABOUT WHAT WE DO NEXT BUT BRING LUNCHES BACK WE'RE GOING TO JUMP RIGHT IN A LITTLE BIT EARLY TO DDR. WE'RE GOING TO BREAK AT ONE BECAUSE THERE WERE A NUMBER OF OUTSIDE INDIVIDUALS WHO HAVE COME TO PARTICIPATE IN THE MEETING WHO READ THE DOCUMENTS AND I THINK WE SHOULD START WITH THEIR COMMENTS BUT NO ONE WAS EXPECTING TO GET STARTED UNTIL ONE SO WHY DON'T WE START, GET A JUMP ON THINGS. >> SURE. SO FIRST OF ALL, I WORKED ON THIS REVISED GUIDANCE DOCUMENT MOVING FROM BOSTON TO WASHINGTON D.C . AND MOVING MY MOTHER DOWN HERE AND BECOMING A GRANDMOTHER. SO I WILL ADMIT THAT I DIDN'T HAVE -- IT'S HARD TO BE A 29-YEAR-OLD GRANDMOTHER. SO I MIGHT HAVE IN OTHER CIRCUMSTANCES HAD MORE TIME TO SPEND ON THIS AND IT'S AN INCREDIBLY COMPLICATED TOPIC. AND THE WAY I SEE THIS DOCUMENT AND THIS ISSUE IS THAT WE WILL TODAY PROVIDE -- YOU WILL PROVIDE A LOT OF GOOD GUIDANCE WHERE WE GO WITH IT BUT I DON'T SEE THIS BEING IN A FORM WHERE WE ARE COME UP WITH ISSUES AND CHANGES AND BE CLOSE TO GETTING IT ON THE WAY. SO THE TOPIC HAS TO DO WITH DECEASED DONOR INTERVENTION RESEARCH ON ORGANS OF DECEASED DONORS SO I WAS WHAT I WILL CALL THE CAPTAIN OF THE DOCUMENT, STEVEN AND NANCY CAME AND, WOOED WITH ME VERY CLOSELY ON IT. THERE ARE PEOPLE WHO HAVE DIFFERENT VIEWS OF DIFFERENT ISSUES INVOLVED IN THIS SITUATION. AND THE QUESTION -- AND OHRP ASKED US TO ANSWER TEN QUESTIONS. SO THE DOCUMENT WHILE THERE MAYBE OTHER PLACES TO GO IN TERMS OF THE CONVERSATION, THE DOCUMENT IS INTENDED TO RESPOND VERY SPECIFICALLY TO THOSE QUESTIONS. THE ONE QUESTION THAT WAS ASKED, ONE OF THE CRITICAL QUESTIONS WAS WHETHER SECRETARY WAIVER WOULD BE APPROPRIATE AND WE DUG INTO THAT MORE SPECIFICALLY AS YOU MAY HAVE SEEN IN THE DOCUMENT, BY DISCUSSING HOW SUCH RESEARCH COULD BE REVIEWED BY FDA, WHERE IT'S REGULATED BY FDA AND THAT IS NOT ACTUALLY SPECIFICALLY IN ANY OF THE QUESTIONS BUT A NATURAL OUTGROWTH FROM THE ONE THAT ASKED ABOUT THE APPROPRIATENESS OF A SECRETARIAL WAIVER. SO THE DOCUMENT THAT I'M GOING TO WORK FROM IS A DOCUMENT THAT I WORKED ON BEFORE THIS MEETING. I HAVE ADDED SOME COMMENTS FROM DIFFERENT PEOPLE IN TO IT SO IT WILL GIVE US TRIGGERS FOR DIFFERENT CONVERSATION. AND SO WHEN YOU SEE DIFFERENT THINGS HERE AND YOU SAY WELL, THAT WASN'T IN MY DOCUMENTS, IT'S THE SAME DOCUMENT IT'S JUST THERE'S BEEN THINGS ADDED TO IT. LET ME JUST SAY ONE THING WHICH IS THAT AT THE OUTSET I THINK WE HAVE A CONSISTENCY ISSUE IN THE DOCUMENT HOW WE REFER TO THE TWO PART CONVERSATION SO IT'S CALLED TWO PART COP SENT OR WHATEVER, I'M NOT SURE IF IT WAS A TWO PART CONSENT PROCESS. AT SOME POINT WE DO NEED TO DECIDE HOW WE WANT TO REFER TO IT. SO DON'T GET ALL TANGLED UP IN KNOTS YET BECAUSE THAT'S NOT A BIG ISSUE WE CAN DEAL WITH THAT, THAT THERE INCONSISTENCIES IN THE DOCUMENT WHETHER IT'S REFERRED TO AS TWO PART CONSENT, TWO PART CONVERSATION, TWO PART PROCESS OR WHATEVER. SO THIS VERY BEGINNING OF THE DOCUMENT IS THE BACKGROUND, SO THERE WAS A NATIONAL ACADEMY OF SCIENCE REPORT ON THIS WHICH BROUGHT THIS TO THE ATTENTION OF OHRP AND I THINK FDA TOO. AND AS YOU CAN SEE THIS IS THE PARAGRAPH THAT TALKS ABOUT HOW SACHRP HAS BEEN ASKED BY OHRP TO CONSIDER CERTAIN ISSUES RELATING TO HOW THIS RESEARCH WOULD BE REVIEWED IN LIGHT OF THE REGULATIONS REGARDING INSTITUTIONAL REVIEW BOARD REVIEW AND RESEARCH INFORMED CONSENT. STEVEN WHEN IT HITS ONE O'CLOCK YOU WANT TO JUMP IN AND CUSS US OFF FOR PEOPLE ON THE PHONE? SO THE FIRST QUESTION IS HERE. AND TALKS ABOUT IF THE TWO-PART PROCESS PROPOSED BY NAM FOR SEEKING INFORMED CONSENT OR IMPLEMENTED WITH THE INFORMATION PROVIDED IN THE SECOND PART, SUBSTANTIALLY DIFFER FROM OR BE SIGNIFICANTLY MORE TIME CONSUMING TO SHARE THE INFORMATION ROUTINELY PROVIDED TO A TRANSPLANT CANDIDATE WHEN OFFERED AS AN ORGAN AS PART OF CLINICAL PRACTICE. SO I SUPPOSE I SHOULD STEP BACK AND SAY THAT THERE'S BEEN SEVERAL MEETINGS FOR THOSE WHO ARE NEW TO THE CONVERSATION WHERE WE HAD REPRESENTATIVES FROM FIRST THE TRANSPLANT COMMUNITY, ABOUT HOW LEGAL COUNCIL TO THE TRANSPLANT COMMUNITY, HOW THIS ACTUALLY WORKS IN REAL LIFE. SO SOME INFORMATION CONTAINED IN THIS DOCUMENT OR SOME GUIDING RECOMMENDATIONS ARE BASED UPON SOME OF THAT INFORMATION AND SOME PEOPLE ARE HERE TODAY AND WE'RE GOING TO -- MORE PEOPLE AT ONE O'CLOCK, I THINK WE ARE HEARING PEOPLE JURY ON. JUMP ON. FEEL FREE IF THAT'S A QUESTION AT ANY TIME. SO THE FIRST QUESTION KIND OF STARTS OFF WITH THAT TWO-PART PROCESS, RIGHT? AND HOW ARE WE GOING TO LOOK AT THAT TWO-PART PROCESS. WE RECEIVED AN AWFUL LOT OF INFORMATION THAT DESCRIBED THE FIRST CONVERSATION AS KIND OF BEING GENERAL AND THAT THERE COULD BE A LOT OF IRB APPROVED PROTOCOLS THAT -- COULD BE PROTOCOLS THAT HAVE BEEN APPROVED BY THE EXPECTATION IS THAT THERE WILL BE MANY MORE APPROVED IN THE FUTURE SO BOTTOM LINE YOU CAN'T RELY ON THAT FIRST CONVERSATION AS A PLACE YOU CAN GO OVER THE IRB APPROVED PROTOCOLS. THE SECOND CONFERENCE COULD HAPPEN ANYWHERE FROM -- CONVERSATION COULD HAPPEN DAYS MONTHS YEARS DOWN THE ROAD I HEARD IT COULD BE FOUR YEARS DOWN THE ROAD SO THEY MIGHT NOT BE CLOSE IN TIME AT ALL AND THAT SECOND CONVERSATION WHICH IS THE ONE WHERE THE INDIVIDUAL IS OFFERED AN ORGAN FOR TRANSPLANTATION COULD TAKE AS LITTLE AS 30 MINUTES AND POTENTIALLY SIX HOURS OR MORE. SO WHAT WE SAY IN OUR DOCUMENT IS BASED UPON THE KNOWLEDGE OF THE DIFFERENCE BETWEEN RESEARCH AND CLINICAL CARE, AND SO FORTH, THE RESEARCH CONVERSATION WOULD PROBABLY REQUIRE MORE TIME AND DISCUSSION THAN COULD RELIABLY BE MADE AVAILABLE DURING THE SECOND CONVERSATION AND PART OF THAT PROBLEM ALSO IS THAT IN THAT FIRST CONFERENCE IF YOU DON'T KNOW WHAT THE RESEARCH WILL BE ON THAT ORGAN IT'S PARRED TO GET INTO PARTICULARS WHAT THAT MIGHT BE. THE OTHER THING WE MENTION -- LET ME JUST MENTION IS THAT WE WERE ASKED TO ASSUME THAT THERE COULD BE SOME RESEARCH THAT'S MINIMAL RISK RESEARCH. MINIMAL RISK IN THE CONTEXT OF THE IRB DEFINITION OF MINIMAL RISK. AND THERE MAY BE A DIFFERENT PERCEPTION MINIMAL RISK FOR CLINICAL PURPOSES BUT WHAT WE ARE GOING TO TALK ABOUT HERE IN THE CONTEXT OF THIS DOCUMENT WE'RE GOING TO TALK ABOUT MINIMAL RISK TOKER THE CONTEXT OF THE IRB REGULATIONS. SO WE HAVE A DISCUSSION WHERE WE TALK ABOUT SOME OF WHAT I JUST SAID, WE DID RAISE -- SO THIS IS WHERE PART OF MY NOTES WAS ADDING THINGS THAT I THOUGHT HAD BEEN LEFT OUT OF THE DOCUMENT. THERE WAS A CONVERSATION AT DIFFERENT TIMES WHETHER THERE COULD BE A COMMUNICATION SYSTEM SET UP SO THAT BETWEEN THE TIME OF THE FIRST CONVERSATION AND THE TIME OF THE SECOND CONVERSATION PEOPLE ON THE TRANSPLANT LIST COULD HAVE ACCESS TO INFORMATION ABOUT IRB APPROVED PROTOCOLS AND ANY NEW PROTOCOLS COULD BE ADDED TO THAT. BUT MY SENSE IN STEVEN CORRECT ME IF I'M WRONG, THERE IS NOT A SYSTEM IN PLACE TODAY AND WE SHOULDN'T RELY ON THAT NOW AS PART OF DISCUSSION OF HOW AN IRB SHOULD MOVE FORWARD. BUT I THINK IT'S IMPORTANT TO RAISE AND KEEP THAT AT THE DOCUMENT. >> I THINK WE DISCUSSED THAT AT LAST MEETING AND WE HEARD A NUMBER OF PERSPECTIVES AND WE ALL FEEL HAVING THAT INFORMATION AVAILABLE IN A WAY THAT IS ACCESSIBLE AND UNDERSTANDABLE TO PARTICIPANTS WOULD BE A GOOD THING. BUT THE ISSUES -- WE DIDN'T FEEL -- WELL, I DIDN'T FEEL IT WAS APPROPRIATE AND WE CAN TAKE THE TEMPERATURE OF OTHERS, TO RELY ON PARTICIPANTS CONTINUING TO USE THAT AS A WAY TO MAKE THE PROCESS FULLY INFORMED. 'S GREAT E RESOURCE, WHEREVER PRACTICAL THAT SHOULD BE DOP DEVELOP AND AVAILABLE TO PEOPLE BUT REQUIRING THEM TO USE IT AS PART OF THE INFORMED CONCEPT PROCESS IS NOT APPROPRIATE SO IT'S NOT ONE OF THE WAYS OUT OF THIS INFORMED CONSENT DIFFICULTY. >> THANKS. DO YOU WANT TO GO TO THE PHONE? >> ACTUALLY YES. SO WE STARTED A LITTLE BIT BEFORE 1:00. THIS SESSION ON THIS RESEARCH WAS SCHEDULE AT ONE SO WE HAVE SEVERAL PEOPLE OUTSIDE JOINING US BY PHONE. I WOULD LIKE TO JUST GIVE THESE DOCUMENTS WE ARE DISTRIBUTED, WE HAVE OUTSIDE EXPERTS. WE DON'T HAVE THE FULL PANEL, WE HAVE REPRESENTATIVES FROM HR SKSA WITH FDA WITH EXPERTISE IN THIS AREA. SO IT WOULD BE A GOOD PLACE TO START WHILE HOPEFULLY EVERYBODY IS AVAILABLE TO HEAR THEIR THOUGHTS ON THE DIRECTION WE ARE TAKING SO FAR. I WILL INVITE DR. FAIPG TO -- FANG TO START IF YOU DOPE MIND, SHARE CONCERNS OR HOLD UNTIL LATER IF YOU FEEL MORE E >> I'M GRATIFIED YOU ARE WORKING ON THIS AND I THINK THIS IS GOING IN A PRODUCTIVE DIRECTION. I THINK THERE'S A STRONG UNDERSTANDING OF LIMITATIONS THAT THE COMMUNITY FACES IN DEALING WITH THIS PROBLEM AND I THINK I CAN MAKE MORE COMMENTS AS WE ARE GOING THROUGH THE DOCUMENT BUT I DON'T HAVE ANY OVERRIDING CONCERNS THAT WE'RE GOING IN THE WRONG DIRECTION. SO THANK YOU VERY MUCH. >> MARK. >> I'M A MEDICAL OFFICER DIVISION OF IMMUNOSUPPRESS SANTS AND ORGAN CELL TRANSPLANTATION. I HAVE BEEN DOING SINCE 1992 SO I HAVE SEEN HOW CLINICAL STUDIES GO AND THE NOTIONS OF INFORMED CONSENT HAVE EVOLVED THERE TOO. WE ANTICIPATE THAT WE WILL GET APPLICATIONS FOR INVESTIGATIVE NEW DRUG EXEMPTIONS OR I IDEs FOR DONOR INTERVENTION, THESE INVOLVE DRUG PRODUCTS THAT PROBABLY IN MY DIVISION. WE WOULD ALSO BE WORKING WITH BIOLOGICS AND WITH DEVICE TO BE CONSULT WITH EACH OTHER. MY EXPERIENCE WITH -- SORRY. MY EXPERIENCE WITH THE PARTICIPANTS IN THE CLINICAL TRIALS FOR TRANSPLANTATION, THAT THEY ARE VERY SOPHISTICATED. THE FIELD OF TRANSPLANTATION RELATIVE TO PATIENTS EDUCATE THEMSELVES EACH OTHER AND PAY ATTENTION TO A LOT OF DETAILS. THIS IS A LOT OF PATIENT SUPPORT, A LOT OF SUPPORT FROM THE NURSING STAFF THERE TOO. SO I THINK THERE ARE PEOPLE THAT COULD HELP WITH THIS. AND PROVIDE SOME TYPE OF CONTINUING I WOULD SAY EDUCATION ABOUT THIS. BECAUSE AS YOU SAID, THE FIRST TIME THEY APPROACH TO BE LISTED THEY DON'T HAVE TO MAKE MANY CHOICES WHAT THEY ACCEPT EXTENDED CRITERIA DONOR OR EXPECT IN SOME CASES ACCEPT DONORS THAT ARE HIGH RISK BECAUSE OF THEIR -- FOR INFECTION, SO FORT. SO THERE'S A LOT OF CHOICES MADE THEN. BUT IT'S OBVIOUSLY GOING TO BE SOMETIMES YEARS UNTIL THEY GET TRANSPLANTED. SO I SEE IT COMING FROM POINT OF VIEW HOW TO DESIGN A CLINICAL STUDY THAT WILL PRODUCE DATA AND BE DONE ACCORDING TO THE PATIENTS WILL BE ADEQUATELY CONCEPTED SO WE HAVE AN ACTIVE INTEREST IN SEEING THAT COME THROUGH. >> I JUST NOTE WHEN WE TALKED BEFORE THE MEETING YOU RAISED THE POINT WHICH I THINK IS CRITICAL IN WHICH WE HAVEN'T BEEN RESPONSIBLE -- RESPONSIVE ENOUGH TO, WHICH IS THAT WE SHOULD HAVE HAD THE VOICES OF THE RECIPIENTS AND TRANSPLANT COMMUNITY ON OUR PANEL BECAUSE THEY ARE THE PEOPLE ACTUALLY DOING THIS. SO THAT'S SOMETHING AS WE -- AS THIS DEVELOPS, IT'S PERHAPS SOMETHING WE CAN SEEK OUT. >> I WOULD MENTION I THINK -- KNOWS MORE ABOUT THIS TOO BUT PROFESSIONAL SOCIETIES AMERICAN SOCIETY OF TRANSPLANTATION, ALREADY HAS DONE SOME OUTREACH TO PATIENTS. ORGANIZED ANNUAL REUNIONS ON THAT TOPIC. I THINK WOULD BE GOOD TO TAP INTO SOME THOAFS ORGANIZATIONS THAT ALREADY HAVE PATIENTS THEY IDENTIFIED EDUCATED ENOUGH TO GIVE A VOICE TO WHAT'S GOING ON. >> ANOTHER SOURCE, UNOS HAS A PATIENT COMMITTEE AND A LOT OF VERY SUPER SOPHISTICATED PATIENTS AND TRANSPLANT AND THEY ARE ALSO DONOR FAMILIES THAT I THINK YOU MIGHT WANT TO CONSIDER INCLUDING, FOR OBVIOUS REASONS. SO THERE ARE A LOT OF RESOURCES TO REACH PATIENTS WHO ARE SOPHISTICATED AND WOULD BE INTERESTED IN PARTICIPATING. >> AS A PRACTICAL MATTER WE HAVE ALREADY BEEN DISCUSSING THIS SINCE JANUARY. BY THE NEXT MEETING WE WILL BE OVER A YEAR AND WE WON'T FINISH TODAY. SO IT WILL BE COMING BACK IN MARCH. I'M A LITTLE SENSITIVE TO RECONVENING. SO THERE A PROCESS WHERE WE -- IF WE FINISH A DRAFT DOCUMENT THAT SACHRP IS HAPPY WITH, IS THERE SOME WAY WE CAN ASK THOSE COMMITTEES REVIEW THAT AND HAVE IT BROUGHT BACK TO THE NEXT MEETING? I WANT TO GET SOME INPUT FROM OGC BEFORE I SAY DEFINITIVELY YES. >> I THINK THOUGH, HOWEVER WHETHER WE ARE ABLE TO DO IT OR NOT, IT IS IMPORTANT THAT WE WANT TO DO IT. >> IF YOU JUST SEND THIS DOCUMENT AND -- BECAUSE IT'S POINTED TO THE 10 QUESTIONS, MAY OR MAY NOT PROVIDE CONTEXT AND THE RATIONALE FOR WHAT'S DRIVING THIS, WHICH IS OF COURSE THE WHOLE ISSUE OF MAKING MORE ORGANS AVAILABLE. YADA YADA, ALL THE BACKGROUND STUFF. SO I WOULD CAUTION THAT THIS DOCUMENT GOES OUT ON ITS OWN WITHOUT SOME OTHER STUFF POTENTIALLY AROUND IT OR SOME CONTEXT SO THAT THERE'S A LOT OF UP TO SPEED AS WE WERE DISCUSSING, IT'S VERY HARD TO GET UP TO SPEED ON THE TOPIC AND IS DOCUMENT IS SORT OF THE FINAL PRODUCT. >> I SEE OUR TASK CHARTING A REGULATORY PATHWAY. SO MAYBE THE APPROPRIATE THING WOULD BE TO FIND AN OPPORTUNITY TO PRESENT THAT FOR US TO PRESENT THAT TO THOSE GROUPS. WHERE IT CAN BE EXPLAINED. >> YOU MIGHT ALSO JUST ATTACH THE MINUTES FROM THE LAST MEETING IN SECTION WHERE WE DISCUSSED ALL THIS. >> THIS IS JIM FROM HRSA. IN BOB WALS CAN CORRECT ME BUT HRSA CAN WORK WITH OHRP TO FACILITATE THIS PROCESS. >> THAT WOULD BE GREAT. THAT'S AN IMPORTANT STEP IN THIS. THEY ARE CLEARLY THE MAJOR STAKEHOLDER COMMUNITY. ANY OTHER COMMENTS FROM FOLKS ON THE PHONE? JOANNE. >> I WANT TO SAY DR. JOHN IS ON THE PHONE FOR FDA, A CARDIO THORACIC SURGEON AND DR. CAROLYN NEWLIN BRANCH CHIEF THAT I DON'T HAVE SEES SOME OF THESE DEVICES. I DON'T KNOW IF THEY HAD ANYTHING TO ADD OR WAIT UNTIL LATER. >> THANK YOU. THERE WILL BE OTHER OPPORTUNITIES. I CAN'T PREDICT HOW LONG WE WILL HAVE THIS CONVERSATION TODAY BUT IF YOU WANT, PLEASE FEEL FREE TO JUMP IN AND -- OR SEND EMAIL OR SOMETHING THAT YOU HAVE A COMMENT AND WE -- TO JULIE AND WE WILL MAKE SURE YOU HAVE AN OPPORTUNITY TO TALK. AND -- >> WE WANT TO ACT NE LEDGE WE ARE ON THE -- ACKNOWLEDGE WE ARE ON THE PHONE. BUT NO COMMENT. >> WE VALUE YOUR INPUT IF YOU FEEL YOU WANT TO GIVE IT AT SOME POINT. >> THANK YOU. >> MICHELE. >> I'M GOING TO PROPOSE, APPROACHING THIS TOPIC A DIFFERENCE WAY. INSTEAD OF GOING THROUGH THE DOCUMENT, I'M GOING TO PROPOSE WE TALK GENERALLY ABOUT WHAT CAN BE DONE IN THAT FIRST CONVERSATION RELATING TO RESEARCH. BECAUSE THAT WILL DRIVE SOME ACCORDINGS FOR THE SECOND PART OF THE CONVERSATION. THAT WILL DRIVE HOW WE THINK ABOUT SECRETARIAL WAIVER AND WHAT THE PARAMETERS ARE. WE ALSO DISCUSS THE INFORMATION WE HAVE INCLUDED ON USING THE PLANNED EMERGENCY RESEARCH PROVISION FOR ANY DDIR RESEARCH THAT'S COVERED BY FDA. IF WE HAVE PA CONVERSATION ABOUT THOSE THREE TOPICS, I THINK IT WILL GIVE ME ENOUGH INFORMATION TO BE ABLE TO WORK THROUGH THIS SPECIFIC QUESTIONS. BUT I'M A LITTLE WORRIED ABOUT GETTING CAUGHT UP IN SOME OF THE SPECIFIC QUESTIONS BECAUSE I THINK ULTIMATELY WHAT WE NEED TO TALK ABOUT IS WHAT'S REALLY GOING TO HAPPEN IN THAT FIRST CONVERSATION, WHAT CAN TAKE PLACE AS IT RELATES TO RESEARCH CONSENT, THEN BASED UPON THAT, HOW DO WE SEE THE SECOND POINT IN TIME AND HOW DOES THE SECRETARIAL WAIVER FIT INTO THAT. IS THAT OKAY WITH PEOPLE OR PEOPLE REFER TO SEE THE DOCUMENT LINE BY LINE? SO I MEAN, IT'S NOT -- THE QUESTION IS DO ADDRESS ALL THESE THINGS BUT IT'S EASIER TO TALK THIS WAY. SO MY UNDERSTANDING -- ACTUALLY I'M GOING TO PUT NANCY KING ON THE SPOT BECAUSE NANCY KING AND I HAD A CONVERSATION JUST A LITTLE WHILE AGO AND SHE SEEMED TO HAVE THIS REALLY UNIQUE FOR THIS GROUP SENSE OF WHAT HAPPENS IN THAT FIRST CONVERSATION AND IT WAS REALLY HELPFUL FOR ME TO HEAR HER >> THANK YOU FOR PUTTING ME ON THE SPOT MICHELE. >> BECAUSE I LIKE YOU SO MUCH. >> IT'S MY UNDERSTANDING, MAYBE DIFFERENTLY IN DIFFERENT CENTERS BUT THE FIRST CONVERSATION IS OR AT LEAST OUGHT TO BE A MAJOR EDUCATIONAL INTERVENTION FOR FOLKS WHO ARE IN THE PROCESS OF GETTING ON THE TRANSPLANT LIST. I KNOW IT'S NOT REALLY A LIST BUT JUST SAY IT THAT WAY. WHICH INCLUDES INFORMATION ABOUT THE PROCESS WHAT HAPPENS WHEN YOU GET A CALL, ALL KIND OF THINGS BUT ALSO INCLUDES INFORMATION LIKE WE HAVE -- WOULD YOU BE WILLING TO ACCEPT AN OFFER OF AN EXTENDED CRITERIA ORGAN, HERE IS WHAT THAT MEANS, HERE ARE WHAT THE GENERAL CATEGORIES ARE. WHEREAS THEN AT THE SECOND POINT IF YOU ARE OFFERED SUCH AN ORGAN YOU ARE GIVEN MORE DETAIL ABOUT THE SPECIFIC ORGAN YOU ARE BEING OFFERED. SO WHAT I WAS THINKING WAS THAT THAT FIRST CONVERSATION IS AN OPPORTUNITY TO INTRODUCE WELL THERE IS THIS CATEGORY OF RESEARCH ORGANS, HERE IS WHAT IT MEANS TO BE IN RESEARCH, HERE ARE SOME GENERAL THINGS TO THINK ABOUT. HERE ARE COMPONENTS OF INFORMED CONSENT, HERE ARE SOME EXAMPLES OF CURRENT RESEARCH GOING ON AND GENERAL CATEGORIES OF RESEARCH THAT MIGHT BE DONE. ALL OF WHICH COULD EASILY BE DONE AS AN EDUCATIONAL MATTER BY PEOPLE NOT CONNECTED WITH THOSE PARTICULAR TRIALS BUT THEN AS A SETUP FOR ARE YOU WILLING TO ACCEPT A RESEARCH ORGAN AND BEAR ALL THESE KINDS OF THINGS IN MIND. WHICH IS IN SORT OF AN EDUCATION L AND GENERAL SETUP FOR THE SECOND CONVERSATION WHEN SUCH AN ORGAN IS ACTUALLY OFFERED. IT'S SIMILAR TO BUT THERE'S MORE TO IT THAN BEING OFFERED AN EXTENDED CRITERIA ORGAN. SO THAT'S MY ASSUMPTION ABOUT THAT FIRST STEP AND WHAT WE RECOMMEND BUILDING INTO THAT FIRST STEP FOR RESEARCH ORGANS. >> CAN WE GET DEFINITIONS AND MAYBE THE EXPERTS CAN HELP US. THERE'S THE PHRASE HIGH RISK ORGAN USED A LOT AND NANCY USED THE PHRASE EXTENDED CRITERIA. IS THAT WHAT YOU SAID? CAN SOMEBODY EXPLAIN THOSE TWO TERMS? >> I THINK TERMINOLOGY IS SUPER IMPORTANT BECAUSE I HAD A COMMENT ABOUT IT. EXPANDED CRITERIA OR EXTENDED CRITERIA, TYPICALLY REFERS TO ORGANS THAT MIGHT NOT FUNCTION IDEALLY UPON TRANSPLANT. SO WE THINK IDEAL DONOR THAT DIES OF TRAUMA AND VARIOUS WAYS WHICH THEN YOU HAVE AN AVERAGE DONOR. THEN YOU HAVE EXPANDED CRITERIA, WHICH CONNOTES BECAUSE IT'S NOT SPECIFIC, CONNOTES A TYPE OF ORGAN THAT MIGHT HAVE INFERIOR EARLY FUNCTION AND/OR INFERIOR LONGEVITY. RISK HIGH RISK INCREASED RISK USED INTERCHANGEABLY WHICH IS UNFORTUNATE, CAN INVOLVE THE FUNCTIONAL ASPECT THAT I JUST MENTIONED. BUT IS OFTEN USED FOR THESE DISEASE TRANSMISSION TYPES OF ORGANS FROM A HEP C DONOR OR A DONOR IN JAIL OR A DONOR USING IV DRUGS. THESE THINGS ARE THEN DIAGRAMMED BECAUSE THESE HIGH RISK TO TRANSMIT DISEASE CAN BE CONSIDERED,PANNEDDED RISK BECAUSE THEY HAVE THIS -- EXPANDED RISK BECAUSE THEY HAVE THIS OTHER TYPE OF RISK AND WE HAVE BEEN TRYING TO TRANSPLANT OR AT LEAST I HAVE BEEN TRYING TO SEPARATE OUT THE FUNCTIONAL RISK ISSUES FROM THE DISEASE TRANSMISSION RISK ISSUES, AND THAT'S FOR A VARIETY OF REASONS INCLUDING THE FACT THAT FOR DISEASE TRANSMISSION YOU EITHER GET IT OR YOU DON'T. AND VERY FEW PEOPLE ACTUALLY GET THE DISEASE. HEP C. BUT THE FUNCTIONAL IS THIS GRADATION OF RISK. SOME WERE DARN WELL, WORDS PRETTY DARN -- THERE'S A GRADATION. SO I THINK WHAT WE SHOULD THINK ABOUT IS EXPANDED CRITERIA AND DEFINE THEM MORE AS A OR USE THEM MORE FUNCTION AND RISK RELATED TO THE PHS, PUBLIC HEALTH SERVICE INCREASED RISK CRITERIA. >> THAT'S HELPFUL. THANK YOU. NANCY, DID YOU WANT TO ADD ANYTHING? OKAY. SO GO AHEAD. >> ARE WE PRESUMING THE NAM REPORT WILL BE IMPLEMENTED BEFORE THIS HAPPENED? CAN WE ASSUME THAT FRAMEWORK EXISTS? >> I THINK THE CONCERN IS THAT I HAVEN'T HEARD ANY ARGUMENTS AGAINST THAT FRAMEWORK. BUT UNTIL OHRP AND FDA FIND IT MEETS REGULATORY REQUIREMENTS I DON'T THINK ANYONE WILL MOVE FORWARD ON IT. FIND A WAY TO HAVE IT MEET THE REGULATORY REQUIREMENTS. FAIR? >> WE ARE STEW MID FOR QUOTE UNQUOTE MINIMAL RISK STUDIES THAT'S BEEN DONE WITH HYPOTHERMIA, WHICH I THINK WE DISCUSSED LAST TIME. AND THAT WAS DEEMED MINIMAL RISK BY SOME PEOPLE BUT THEN OTHER PEOPLE HAVE CHIMED IN AND HAD ISSUES WITH THAT WHERE MINIMAL RISK STUDIES SOME IRB SAYS YOU DON'T HAVE TO DO ANY SORT OF INFORMED CONSENT AND IN THAT CASE THERE WAS EVEN A -- THERE WAS NO SPECIFICATION OF NOTIFYING PEOPLE INFORMING PEOPLE. STUDIES BEYOND THAT, I DON'T THINK, HAVE ANY REAL PATHWAY TO BEING DONE RIGHT NOW ON ANY SORT OF SIGNIFICANT VOLUME BASIS. >> I'M NOT CLEAR ON WHAT THE SCOPE OF OUR PARTICULAR TASK IS TODAY GIVEN THAT THEY WANT TO SET SOMETHING UP THAT WILL ALLOW IT TO BE THIS RESEARCH TO BE DONE IN THIS BROADER CONTEXT BUT WE ARE NOT SUPPOSED TO ASSUME THAT EXISTS YET. SO WHAT ARE WE TRYING TO DO? >> I DON'T REMEMBER SPECIFICS OF THE QUESTION BUT AMONG QUESTIONS WE FOUND THAT FRAMEWORK WAS APPROPRIATE. AND I THINK WE DID. WE DIDN'T COME UP WITH ANYTHING BETTER. AND MOST OF OUR WORK HAS BEEN -- SO THERE'S THE MINIMAL RISK WHICH WE CAN SPEND A COUPLE OF MOMENTS ON BECAUSE I THINK PARTICULARLY WITH OUR CLINICAL COLLEAGUES LISTENING, I THINK IT'S WORTH DESCRIBING WHY WE HAVE ANY TROUBLE WITH THAT AT ALL BECAUSE I THINK IN THE CONTEXT OF HAVING A TRANSPLANT, IT'S PRETTY CLEAR IN THE COMMON SENSE AND CLINICAL USE OF THIS IS MINIMAL RISK PARTICULARLY ON TOP OF WHAT YOU ARE GOING THROUGH AS TRANSPLANT, IT'S A NO BRAINER. BUT THE REGULATORY DESIGNATION MINIMAL RISK WHICH OPENS THESE THINGS LIKE WAIVER OF CONSENT MEANS SOMETHING SPECIFIC. IT MEANS NOT GREATER THAN RISKS ENCOUNTERED IN EVERY DAY LIFE AND THAT'S BEEN INTERPRETED TO BE NOT FOR PEOPLE ON THE TRANSPLANT LIST BUT FOR THE AVERAGE PERSON. SO THAT CREATES A BARRIER TO US RELYING ON THAT DESIGNATION EVEN FOR THINGS LIKE HYPOTHERMIA RESEARCH. SO THAT'S WHAT THAT WHOLE DEBATE IS ABOUT. I THINK IT'S WORTH MAKING THAT EXPLICIT BECAUSE LIKE THEIR CONSENT AND RECONSENT DISCUSSION, WE TALK IN REGULATORY SPEECH AND IF YOU ARE NOT IMMERSED IN THAT, SOME OF WHAT WE ARE SAYING DOESN'T MAKE SENSE AT ALL. I DON'T THINK ANYONE IS ARGUING THAT THE RISKS OF THESE THINGS ARE SMALL, WE ARE JUST TRYING TO FIND A WAY TO OPEN THE REGULATORY PATHWAYS THAT THIS ALLOWS. SO WE WERE ASKED SPECIFICALLY NOT TO OPINE WHETHER THIS COULD BE MINIMAL RISK PER REGULATIONS OR NOT BUT SIMPLY DISCUSS IN THE QUESTIONS HOW WE WOULD HANDLE A STUDY DEEMED TO BE MINIMAL RISK. SO AS TO TAKE THAT DISTINCTION OFF THE TABLE. I THINK WE TRIED TO ANSWER THAT. IN THE QUESTIONS AND GENERALLY TOOK THE POSITION IT WOULD BE LIKE ANY OTHER MINIMAL RISK STUDY. THERE'S CRITERIA YOU HAVE TO PASS TO GET WAIVER OF CONSENT, SOME WOULD BE STRAIGHT FORWARD, SOME MIGHT NOT. BUT THAT'S WHAT YOU HAVE TO DO. I THINK THAT THAT'S PROBABLY THE BEST SUMMARY OF THAT. I DON'T -- WE COULD GET DISTRACTED TO A CONVERSATION WHETHER THIS MET CRITERIA FOR RIGLATORY MINIMAL RISK AND DID OR DIDN'T AND I DON'T THINK THAT'S WORTH SPENDING OUR TIME ON. ASSUME IT DOES, SOME OF IT DOESN'T. >> JUST TO SPEAK TO YOUR QUESTION. I THINK THIS INFORMED CONSENT FOR THE RECIPIENT WHO IS THE HUMAN SUBJECT AND HOW TO ACHIEVE THAT REGULATORY COMPLIANCE IS THE IMMEDIATE BARRIER. BUT LET'S SAY YOU WORK IT OUT HERE AND OHRP SAYS YES WE WILL TAKE THIS, THE SECRETARY DOES THAT, YADA YADA, THE NEXT BARRIER WOULD BE POTENTIALLY TO SET UP OR DEAL WITH THIS SINGLE IRB, THE DROC. THERE'S A SERIES OF THINGS TO PUT THE INFRASTRUCTURE TOGETHER TO ACTUALLY ALLOW THE TRIALS TO GO FORWARD. BUT ONE COULD IMAGINE WITHOUT SOME OF THESE INFRASTRUCTURE -- THERE COULD BE SOME INROADS AS LONG AS WE UNDERSTAND HOW TO DEAL WITH HUMAN SUBJECTS. THAT'S THE SUPER FRIGHTENING AND CONFUSING PART. >> PART OF -- I'M STRUGGLING WITH, MAYBE I'M JUST BEING DENSE HERE. BUT TO ME THE MOST DIFFICULT THING IS HOW DO YOU GET THE NECESSARY INFORMATION TO THE PATIENTS IN A REASONABLE PERIOD OF TIME. AND IF THE DROC EXISTED THERE WOULD BE A PLACE WHERE WE COULD SHARE THAT INFORMATION. BUT IF WE CAN'T ASSUME THAT THAT EXISTS, THEN HOW DO WE PROPOSE TO MAKE THAT INFORMATION AVAILABLE? WE CAN'T GO FORWARD WITHOUT IT. >> I THINK THERE COULD BE -- BECAUSE TRANSPLANT IS A NATIONAL ENTERPRISE AND THERE ARE NATIONAL STRUCTURES IN PLACE SUCH AS UNOS OPTN. , WE COULD FIND A WAY TO HAVE A WEBSITE THAT IS PATIENT FACING, THAT COULD -- WE COULD OPERATIONALLIZE THAT BECAUSE TRANSPLANT IS A NATIONAL ENTERPRISE AND WE HAVE WAYS TO REACH EVERY SINGLE TRANSPLANT PATIENT. SO I THINK THOSE THINGS ARE DOABLE. >> I'M BOB WALSH, HRSA TRANSPLANTATION. THANK YOU, LARGE PART IS WHAT I WANT TO SAY. FROM OUR PERSPECTIVE, THE FIRST QUESTION NEEDS TO BE ADDRESSED IS QUESTION BEFORE THIS GROUP NOW. HHS AND HRSA IS VERY SUPPORTIVE OF THE DIRECTION THAT CAME OUT OF THE NAM REPORT AND WE ARE VERY INTERESTED HOW WE CAN PUT THOSE STRUCTURES IN PLACE. BUT IT'S A CHICKEN OR EGG THING. WE NEED TO MAKE SURE THAT WE WERE ABLE TO DO IT. BEFORE WE START MAKING DETAIL DECISIONS ON HOW WE WOULD DO IT. >> I WOULD LIKE TO CLARIFY, I DON'T THINK OUR CHARGE IS TO REVISIT THE CONCLUSIONS OF THE NAM REPORT. I THINK THEY HAD AN OPPORTUNITY TO DO A DEEPER DIVE, THEY HAD BETTER EXPERTISE SPECIFIC EXPERTISE. IF THESE ARE THE RECOMMENDATIONS THEY CAME OUT WITH AS FAR AS THE DROC, WE MADE COMMENTS ON THEM TRANSPLANT SPECIFIC IRB, FINE. WE ARE SPECIFICALLY TASKED WITH HOW TO MAKE THIS WORK, PARTICULARLY WITH REGARDS TO CONSENTS AND MEETING THE REGULATORY REQUIREMENTS. SO I CO-OPTED A BUNCH OF PEOPLE WAITING TO TALK. I DON'T KNOW WHO WAS FIRST. >> MY COMMENT IS MORE GENERAL, APPRECIATE AND ENDORSE BRINGING THE PATIENTS AND THEIR FAMILIES TO HELP GUIDE THIS BUT I'M VERY CONCERNED ABOUT THE LANGUAGE USED TO DESCRIBE PEOPLE AS SOPHISTICATED OR EDUCATED. I THIT'S EXCLUE -- THINK IT'S EXCLUSIVE AND IS IN OPPOSITION TO THE PRINCIPLE OF JUSTICE AND MAKING SURE THAT WE ARE BEING FAIR ABOUT WHAT -- WHO COULD BENEFIT OR MIGHT BE HARMED FROM RESEARCH. >> BEFORE WE MOVE ON, COULD I PUT YOU ON THE SPOT? BECAUSE THAT'S A DIFFERENT LENS THAN WE ARE USED TO USING AND IT WOULD BE HELPFUL FOR YOU TO POINT US TO A SENTENCE IN THE DOCUMENT. SO WE KNEW EXACTLY WHAT WE SHOULD BE THINKING TWICE ABOUT. >> I DON'T KNOW THERE'S A SENSE IN THE DOCUMENT BUT IN THE DISCUSSIONS AS WE WERE GOING AROUND ABOUT BRINGING PEOPLE TO THE TABLE, SEVERAL PEOPLE MADE POINTS ABOUT HOW SOPHISTICATED THE TRANSPLANT POPULATION IS AND HOW WE CAN BRING THESE PEOPLE WHO ARE WELL RESOURCED AND CONNECTED TO SUPPORT GROUPS TO GET THEIR OPINIONS TO INFORM THE PROCESS. >> I'M GOING TO MAKE A COROLLARY REMARK AND JUST TO ACKNOWLEDGE WITH THANKS THE READING PROVIDED TO THE DMI FROM THE 20TH ANNUAL STATE-OF-THE-ART WINTER SYMPOSIUM. ON -- BY THE AMERICAN SOCIETY OF TRANSPLANT SURGEONS. WHICH IS ESSENTIALLY A SURVEY CONDUCTED OF INDIVIDUALS WHO ARE ON A TRANSPLANT LIST, TO PROVIDE INPUT IN TERMS OF THEIR PERSPECTIVES. I THINK OUR PRIOR MEETING WHERE THIS TOPIC WAS RAISED WAS MISSING THE VOICE OF THE PATIENT. SO I THINK THAT THIS IS A VERY GOOD START BUT TO CONSWELO'S POINT ONE CRITIQUE OF THE SURVEY WAS THAT IT WAS NOT FULLY REPRESENTATIVE. SO I WOULD ENCOURAGE THE BETTER INFORM OURSELVES WITH RESPECT TO REPRESENTATIVENESS OF THE TRANSPLANT RECIPIENT POPULATION. THE OTHER POINT, I MAY BE JUMPING AHEAD, BUT IT WAS A POINT THAT RENEE HIGHLIGHTED THAT THE CONSENT PROCESS IS ONE THAT'S GOING TO BE THE ABILITY OF THE RESPECTIVE SE SIP YENT TO RESPOND IN AN INFORMED WAY IS NOT A CONSTANT. IN CERTAIN ORGAN TRANSPLANTS THERE IS GOING TO BE POTENTIALLY A CHANGE IN MENTAL STATUS. WHO HAD TRANSPLANTS FOR EXAMPLE WHERE THERE MAYBE THE INDIVIDUAL PLACED ON A LIST EARLY ON THOUGHTFUL RESPONSE THAN WHEN AN ORGAN BECOMES AVAILABLE SO THAT'S -- THERE ARE SOME INHERENT CHALLENGES WITH THIS TWO STEP PROCESS, INDEPENDENT OF THE YOU ARE U URGENCY OF THE DECISION MAKING. >> DISPLILD POINT OUT IF WE CAN'T -- >> I WOULD POINT OUT IF WE CAN'T SOLVE FOR PEOPLE WHO ARE COMPETENT, SO I WOULD HOPE WE USE THE SAME MODEL FOR COMPETENCE THAT WE USE IN OTHER SETTINGS AND WE HEARD THAT FROM THE FROM THE TRANSPLANT COMMUNITY, EVEN IF THEY'RE NOT COMPETENT FOR SECOND TRANSPLANT, THERE'S ALMOST ALWAYS LAR INVOLVED IN THIS SITUATION BECAUSE IT'S A FORESEEABLE SITUATION SO IN THIS CASE THE SAME CONSTRAINTS TIMING CONSTRAINTS APPLY TO THE LAR. SO I THINK THAT THAT'S NOT THE PRIMARY PROBLEM. I THINK WE NEED -- AND CONSUELO, I'LL CHALLENGE YOU. THE POINT YOU BRING UP IS SOMETHING WE HAVE ALL THE TIME. AND JUST AS A PRACTICAL MATTER, WE HAVE WHEN WE ASK FOR THE VOICE OF THE PATIENT OR THE VOICE OF THE PARTICIPANT, THE PEOPLE WHO STEP UP AND VOLUNTEER ARE TYPICALLY HAVE IN THE PATIENT -- THEIR RESEARCH ADVOCATES, THEIR NOT TYPICAL -- THAT'S JUST THE STRUCTURAL PROBLEM. IF YOU -- PLEASE KEEP REMINDING US OF THAT AND IF WE CAN BRAINSTORM WAYS, IT'S DIFFICULT FOR IRBs, DIFFICULT FOR THE WHOLE COMMUNITY. >> HAPPY TO DO THAT. WE ARE DOING THAT WITH ALL OF US RESEARCH PROGRAM NOW, WE HAVE GOT PEOPLE FROM AROUND THE COUNTRY, DIFFERENT BACKGROUNDS, DIFFERENT EDUCATIONAL LEVELS THAT WE PREPARE AND EMBED INTO GOVERNANCE COMMITTEES TO PROVIDE GUIDANCE. IT DOES TAKE WORK, RESOURCES, SOMEONE WHO IS KNOWLEDGEABLE BUT I'M SURE WITHIN UNOS THERE ARE PEOPLE WHO ARE ARE INTERACTING SPECIFICALLY WITH MINORITY POPULATION, PEOPLE IN RURAL COMMUNITIES, MAKING SURE THEY HAVE THE INFORMATION THEY NEED TO MAKE INFORMED DECISIONS. BUT THAT WOULD PROBABLY NEED TO BE A DIRECT ASK TO IDENTIFY THOSE PEOPLE TO SAY HEY, CAN YOU HELP US FIND SOMEONE WHO CAN GIVE GUIDANCE. >> BACK TO MY SHE WOULD'S CHALLENGE -- MICHELE'S CHALLENGE TO ARTICULATE BUT IF NANCY WANTS TO FOLLOW-UP ON THIS CONVERSATION I'LL DEFER TO YOU THEN DO MY COMMENT. >> THANK YOU, BECAUSE I WAS EXACTLY WHAT I WAS GOING TO DO. THIS IS ACTUALLY REALLY IMPORTANT BUT IT ALSO GOES BACK TO SOMETHING THAT'S STEVEN SAID EARLIER WHICH IS ON THE ONE HAND WHAT WE ARE TRYING TO DO IS IDENTIFY WHAT -- HOW CAN THE RESEARCH -- THE REQUIREMENTS FOR INFORMED CONSENT TO RESEARCH BE ADEQUATELY MET UNDER THE CIRCUMSTANCES OF THE TRANSPLANT SETTING. AND WE ARE ALSO TALKING ABOUT ALL THE WAYS WHICH MORE INFORMATION CAN BE PROVIDED TO FOLKS AWAITING TRANSPLANT WHO ARE INTERESTED IN RECEIVING OFFERS OF RESEARCH ORGANS WHICH ARE ALL TO THE GOOD AND REALLY IMPORTANT TO DO BUT WHAT WE HAVE TO AVOID, THIS GOES TO C OBJECTIONNSUELO'S POINT, WE HAVE THE AVOID SAYING ALL WE NEED TO DO IS MAKE SURE THAT EVERYBODY LOOKS AT THE WEBSITE AND THEN WE DON'T HAVE TO WORRY ABOUT THE CONSENT FORM AND PROCESS. SO WE HAVE TO KEEP THOSE TWO THINGS SEPARATELY, WHAT WE NEED TO DO IS DO WHAT'S RIGHT FOR RESEARCH PARTICIPANTS WITHOUT REQUIRING THEM TO DO A WHOLE LOT OF TAKING UP OF WHAT'S OFFERED BUT ALL THOSE RESOURCES SHOULD STILL BE OFFERED >> RIGHT. SO LET ME ARTICULATE WHAT I THINK NANCY DESCRIBED AS STEP ONE AND REPHRASE IT AND SEE IF WE ARE ON THE SAME PAGE. BASICALLY IF I'M A CANDIDATE FOR TRANSPLANTATION, I'M ENTERING THAT PROCESS HOWEVER IT'S LISTED OR HOW WE DESCRIBE THAT, THERE'S A SIT DOWN TO TELL ME WHAT THAT REALLY ENTAILS. AS PART OF THAT SIT DOWN, THERE IS A DESCRIPTION OF THE EXPANDED OR EXTENDED CRITERIA, DESCRIPTION OF THE HIGHER RISK CRITERIA AS DESCRIBED, WHERE I ASSUME THAT AS PART OF THAT PROCESS THERE WILL BE SOME SORT OF E LISSATION OF MY PREFERENCE --S, CONSIDER IT ET CETERA NOT NECESSARILY BINDING ON FUTURE DECISION BUT GUIDANCE WHETHER TO APPROACH ME OR SOMEONE ELSE THERE WHO SAID I WOULD DEFINITELY TAKE THAT, IF I'M HESITANT YOU ONLY HAVE TEN MINUTES, YOU GO THE FERN WHO SAID THEY WOULD BE OPEN TO THAT. SO IT SOUNDS LIKE WHAT WE ARE ADDING TO THAT PROCESS IS A THIRD CATEGORY. WHICH IS DECEASED DONOR ORGANS THAT HAVE GONE THROUGH SOME RESEARCH PROCESS. IN THAT CONTEXT YOU CAN'T SPECIFY WHAT PROTOCOL THAT WOULD BE FROM, YOU CAN'T SPECIFY WHETHER WE WANT TO ELICIT RISK PREFERENCE IN THAT CONTEXT, WOULD BE ANOTHER DISCUSSION BUT THE POINT IS WE HAVE ADDED A THIRD CATEGORY WHERE YOU WOULD ELICIT MY PREFERENCE THERE AS WELL. SAYING -- AND IF I SAID NO WAY, THEN AGAIN YOU MIGHT NOT APPROACH ME AS OPPOSED TO MY NEIGHBOR. WHO SAID SURE I WOULD CONSIDER THAT. OR YOU MIGHT -- IF IT'S AN EASY QUESTION. SO EFFECTIVELY WE ARE ADDING A THIRD GROUP IF YOU WILL. A THIRD GROUP AND ELICITING A PREFERENCE. WE ARE NOT GETTING INFORMED CONSENT BECAUSE YOU DON'T REALLY KNOW WHAT TO DO AT THIS POINT. SO THAT -- THAT'S MY UNDERSTANDING OF WHAT WE ARE TALKING ABOUT. I WANT TO MAKE SURE WE ARE ON THE SAME PAGE. >> THAT GOES TO A REALLY IMPORTANT POINT. THAT IS HOW WE ARE THINKING OF IT. IF YOU THOUGHT OF THAT DECISION TO ACCEPT A RESEARCH ORGAN AS THE FIRST STEP TO PARTICIPATING IN RESEARCH, THEN YOU HAVE TO TREAT IT AS A RESEARCH CONSENT. THE OTHERS ARE CLINICAL DISCUSSION. SO THEY ARE DIFFERENT REGULATORY IMPLICATIONS, SO WE HAVE TO DECIDE, THE -- WE HAVE TO DECIDE. I THINK THE IMPLICATIONS ARE IF IT'S NOT A RESEARCH CONCEPT, IF IT'S A CONSENT TO HAVE PRESENTED A RESEARCH OFFER AT SOME LATER DATE, JUST LIKE THE EXTENDED CRITERIA DONORS ARE THE INFECTIOUS DISEASE ISSUES. THAT DOESN'T -- I DON'T THINK THAT'S REALLY NOT PARTICIPATION IN RESEARCH. SO WE DON'T NEED TO INVOKE ALL OF THE PARTS OF 116. THAT CAN BE MUCH SIMPLER. THE DOWN SIDE OF THAT THEN IS THAT WE MIGHT WANT TO TREAT IT ADS AN NON-REEARCH CONSENT BUT SAY EXPLICITLY WHAT NEEDS TO GO INTO IT BECAUSE YOU WON'T HAVE A CHANCE DOWN THE ROAD. >> CAN WE GET CONFIRMATION FROM THE EXPERTS IN THE ROOM THAT WHAT WE ARE TALKING ABOUT DOES HAPPEN? THAT THERE IS THIS FIRST CONVERSATION THAT INVOLVES AN EDUCATION EFFORT AND COVERS THE EXPANDED CRITERIA AND THE HIGH RISK? IS THAT ACTUALLY HAPPENING ALL THE TIME? >> I WOULD SAY THAT THAT IS PROBABLY HAPPENING. MOST OF THE TIME AND THAT THAT IS PAD JUSTED BASE -- AND THAT IS ADJUSTED BASED ON THE LOCAL CONDITIONS. I KNOW UCSF, THE BEST OF COURSE, SO FOR EXAMPLE, IF OUR KIDNEY WAITING LIST IS EIGHT YEARS LONG, THEN WHAT YOU THINK ON DAY ONE WHEN YOU KIND OF VERY FAMILIAR WITH DIALYSIS AND TRANSPLANT SOUNDS LIKE YOU ARE JUMPING UP INTO A FOREIGN ORBIT, IS VERY SCARY AND THEREFORE WE DON'T GET IN -- WE DO INTRODUCE THE IDEAS BUT WE DON'T DRILL DOWN ON ALL -- SO THE LEVEL OF DETAIL, THE APPROPRIATENESS OF THE MESSAGE, IS REALLY DEPENDENT ON THE OTHER HAND IF I'M AT A TRANSPLANT CENTER WHICH INSTEAD OF SEEING 2000 PATIENT AS YEAR SEES 50 PATIENTS A YEAR, MY WAITING LIST IS TWO YEARS LONG, THEN I MIGHT DO SOMETHING DIFFERENT. IT'S ALSO REALLY IMPORTANT TO REMEMBER THAT PEOPLE'S PREFERENCES CAN AND SHOULD AND DO CHANGE OVER TIME. SO I THINK WHILE THIS TWO STEP THING IS DEFINITELY THE WAY TO GO, I THINK YOU GUYS SHOULD CONSIDER WHETHER YOU THINK IT WOULD BE IMPORTANT TO HAVE STEP 1A AND MAYBE A 1B AND A 1C BECAUSE YOU DON'T WANT TO TAKE THE PREFERENCES THAT ARE NECESSARILY EXPRESSED AT THE GET GO WHERE PEOPLE MAY BE THE LEAST INCLINED TOWARDS TRANSPLANTS TO BE THEN NOT REVISITED, IF POSSIBLE, ET CETERA. >> I'M JUST A LITTLE CONCERNED ABOUT US MAKING ASSUMPTIONS ABOUT WHAT GOES ON IN A FIRST CONVERSATION. THEN HAVING WHAT WE THINK IS APPROPRIATE NUMBER 2 CONDITIONED UPON THOSE THINGS HAPPENING. IF THEY ARE NOT ACTUALLY HAPPENING. >> MICHELE, I HERE HESITATION JUST FROM AN EPIDEMIOLOGIC PERSPECTIVE, YOU MAY NOT KNOW WHAT'S GOING ON EVERYWHERE. SO FROM MY STANDPOINT I WOULD USE THE BEST PRACTICE APPROACH IN THAT REGARD AND NOT TRY TO USE A DEMOGRAPHIC ARGUMENT ABOUT WHAT IS HAPPENING. BUST TWO QUICK COMMENTS. I VERY CAREFULLY USED THE LANGUAGE ELICIT A PREFERENCE. NOT GET INFORMED CONSENT SO I DON'T THINK THIS FIRST CONVERSATION IS A CONSENT PROCESS. I DON'T EVEN THINK IT'S A CONSENT PROCESS TO THE EXPANDED -- IT'S THE FIRST PREFERENCE. THAT'S A SEPARATE QUESTION TO DEPENDING HOW LONG I'M ON THE LIST HOW I AM UPDATED, HOW I UNDERSTAND, HOW AS MY DISEASE PROGRESSES MY RISK PREFERENCES CHANGE. THAT'S A WHOLE SEPARATE QUESTION AND HOW THAT'S UPDATED, ET CETERA. BUT I THINK THAT FIRST CONVERSATION IS NOT A RESEARCH CONSENT, IT'S AN E E LISSATION, ABOUT THE NEXT SET OF OPTIONS AND IF I CHANGE MY MIND HOW THAT'S INCORPORATED, AT THE TIME OF THE ACTUAL HERE IS AN ORGAN, WHAT DO WE DO, THAT'S THEN A THIRD STEP. SO I THINK WE NEED TO LOOK AT EACH OF THOSE PROCESSES VERY SEPARATELY. >> CAN I SUGGEST SIMPLIFYING ASSUMPTION THAT I WANT COMMENTED ON BY FDA AND BY OHRP TO SEE IF IT MEETS REGULATORY SNUFF. THE IDEA IS YOU HAVE THE SECOND CONVERSATION. RESEVERAL TO CONSENT, TO RECEIVE THE ORGAN -- MANIPULATED UNDER A SPECIFIC PROTOCOL. YOU HAVE OPPORTUNITIES BEFORE THAT. AND I THINK WHAT WE HAVE TO BE ABLE TO SAY IS THAT YOU HAVE TO WRITE AT SOME INFORMATION BEFOREHAND. I DON'T THINK GIVEN THE VARIABILITY YOU DESCRIBE WHICH IS GOING TO BE SITE DEPENDENT CLINICAL PARTICIPANT DEPENDENT, EVERYTHING, I DON'T THINK IF WE DON'T NEED TO DO IT FOR REGULATORY PURPOSES, I DON'T THINK WE WANT TO LOCK IN THAT THERE IS A SPECIFIC CONVERSATION THAT COVERS THESE SPECIFIC POINTS AT THIS POINT IN TIME. I THINK WE WANT TO BE ABLE TO SAY THOUGH THAT BEFORE YOU HAVE THAT SECOND CONVERSATION, UNLESS THERE ARE EXTENUATING SIXER, THESE THINGS -- CIRCUMSTANCES, THESE WOULD HAVE BEEN DISCUSSED BEFORE BECAUSE WE WANT TO TAKE -- FROM MY PERSPECTIVE, WE WANT TO UNBURDEN THE SECOND CONVERSATION WHICH WE KNOW IS GOING TO HAPPEN IN A VERY LIMITED PERIOD OF TIME UNDER A LOT OF PRESSURE, MAYBE PERCEIVED AS A LIECH OR DEATH DECISION. THERE'S SO MANY PIECES THAT DON'T MEET OUR GENERALLY ACCEPTED STANDARDS FOR INFORMED CONSENT, THAT THE MORE WE CAN PRE-LOAD THAT THE BETTER OFF WE ARE. I DON'T THINK IT MATTERS FOR THAT SECOND DISCUSSION WHICH IS THE PROBLEMATIC ONE. HOW MANY PEOPLE CHANGE THEIR MINDS. IF WE GO IN THE SECOND TIME WITH ASSUMPTION THIS MATERIAL IS CONVEYED AT SOME POINT, THAT WOULD BE VERY HELPFUL, IF WE CAN'T DO THAT IT'S MUCH MORE DIFFICULT. >> I'M A LITTLE WORRIED ABOUT -- ABOUT ASSUMING THOUGH THAT CERTAIN THINGS HAVE HAPPENED IN THE FIRST CONVERSATION. I MEAN, I -- THAT'S A CONCERN THAT I HAVE BASED ON WHAT I'M HEARING FROM THE EXPERTS. >> I DON'T THINK IT CAN BE ANY ASSUMPTION ON THE PART OF AN INDIVIDUAL THAT AFTER THEY HAVE HAD THAT FIRST CONVERSATION JUST LAID OUTLET'S SAY THE -- OUT, LET'S SAY THE BROAD FRAMEWORK, I DON'T THINK THERE'S ANY ASSUMPTION THAT THERE'S ANY INFORMATION UPDATED BEFORE THE TIME OF THAT SECOND CONVERSATION BECAUSE THAT SECOND CONVERSATION COULD BE EIGHT YEARS LATER, SEVEN SIX FIVE FOUR THREE TWO ONE, A MONTH LATER, IF IT RELIES ON A WEBSITE, DO I HAVE WEB ACCESS. WE HAVE TO ASSUME IGNORANCE. >> LET ME ASK SOMETHING ELSE THEN BECAUSE AS A VERY PRACTICAL MATTER WHEN YOU HAVE AN OFFER, WHEN YOU HAVE AN ORGAN AVAILABLE, YOU KNOW YOU HAVE A LIST OF PEOPLE WHO HAVE AGREED TO ACCEPT THAT TYPE OF ORGAN. SAY IT'S AN EXTENDED DO MORE ORGAN, YOU DON'T GO TO PEOPLE WHO HAVEN'T SAID THEY WOULD ACCEPT EXTENDED DONOR ORGAN, DO YOU? >> YES AND NO. SO THE PROBLEM IS BECAUSE THE -- IF YOU JUST EVEN LOOK AT AN INCREASE RISK ORGAN, WE KNOW FROM DATA THAT THERE'S CERTAIN TYPES OF BEHAVIORS, IV DRUG USE AND MEN WHO HAVE SEX WITH MEN THAT HAVE THE HIGHEST -- POSE THE HIGHEST RISK OF TRANSMISSION. SO UNLESS YOU ARE ABOUT TO DIE, IF YOU SAID NO, WE DON'T ASK YOU, IF YOU ARE ABOUT TO DIE, WE WILL ASK YOU FOR THAT. HOWEVER, IF THE RISK DESIGNATION IS BASED ON THIS DONOR HAVING BEEN IN THE HOSPITAL AND DURING THE PROCESS OF DEATH GETS DIALYSIS, THAT'S LABELED INCREASE RISK IN THE EXACT SAME WAY BUT WE KNOW FROM DATA THAT THE RISK OF TRANSMISSION IN DIALYSIS AND HOSPITALS IS ALMOST NOTHING. SO THEN WE WILL APPROACH SOMEBODY WHO IS APPROPRIATE FOR THAT ORGAN EVEN THOUGH THEY SAID NO, I DON'T WANT INCREASE RISK. AND WILL SAY HEY LOOK THIS IS NOT -- SO THESE ARE ALL KINDS OF SHADES OF GRAY BUT SOMETHING THAT'S VERY HIGH RISK IN ONE WAY OR ANOTHER, WE WOULD NOT APPROACH A PERSON WHO IS DECLINED. IF IT'S LOW RISK THEN WE MIGHT. I'M USING THE RISK FUNCTIONALLY AND DISEASE WISE. >> I HAVE BEEN OPERATING ON THE ASHUM SUM SHUN THAT WE ARE TALKING ABOUT A TWO-STEP PROCESS DESCRIBED IN THE NAM REPORT. WHAT WE ARE NOW TALKING ABOUT IS NOT THAT. WHAT WE ARE TALKING ABOUT IS WILLINGNESS DISCUSSIONS EDUCATION SIGNALING BUT THE RESEARCH CONSENT IS THE SECOND CONSENT. AND I'M NOT SAYING BAD OR GOOD, WE NEED TO HAVE CERTAIN THINGS ESTABLISHED BEFORE WE CAN EVEN OPINE ABOUT HOW THESE MAKE THE REGULATION. >> I THINK YOU CAN LEND SHAPE TO THE DISCUSSION. I WOULD SAY 15 YEARS AGO, 10 YEARS AGO WHEN THE INCREASED RISK TRANSMISSION -- DISEASE TRANSMISSION ORGANS WERE FIRST SORT OF ON THE SCENE BECAUSE WE GOT MORE DESPERATE TO USE ORGANS, THERE WAS A LOT MORE VARIABILITY ABOUT HOW TRANSPLANTS CENTERS WERE HANDLING. NOW THAT THIS IS SORT OF PART OF THE ROUTINE I WOULD SAY THERE'S MUCH LESS VARIABILITY THERE'S MORE BEST PRACTICES BEING FOLLOWED. I THINK THIS TYPE OF DISCUSSION, IF YOU PROVIDE SOME GUIDELINES, THEY MAY NOT BE -- I DON'T KNOW WHAT RECOMMENDATIONS GUIDELINES RULES, THERE'S ALL SHADES OF GRAY. I THINK THEY DO PROVIDE A BEST PRACTICE FRAMEWORK FOR TRANSPLANT CENTERS TO WORK THROUGH. I WOULD ASK YOU PERHAPS TO CONSIDER ABANDONING THE FIRST AND THE SECOND. BECAUSE I THINK THIS IS KIND OF PROVIDING A FRAMEWORK THAT'S RESTRICTIVE. YOU MIGHT WANT TO SAY INITIAL AND THEN YOU MIGHT WANT TO SAY FINAL. BECAUSE NO MATTER WHAT, THE DAY OF THE ORGAN IS -- WELL IT'S FINAL FOR THAT ORGAN SO MAYBE THAT'S NOT A GOOD WORD BUT I WOULD MAYBE GET AWAY FROM MAKING IT STRICTLY ONE AND TWO IMPLICATING THAT THERE'S THESE TWO POINTS IN TIME. >> IN ORDER FOR US TO HAVE THE MOST FLEXIBILITY, I THINK MAYBE WE SHOULD -- LET'S DISCUSS THIS FOR A MOMENT, I THINK IT'S RESPONSIVE TO MY SHE WOULD'S ORIGINAL QUESTION. -- MICHELE'S ORIGINAL QUESTION. LET'S TALK ABOUT THIS IS ALL CONSENT TOO. WE CAN TALK BEST PRACTICE AND WHAT PEOPLE SHOULD BE DONE AND HOW PEOPLE SHOULD HAVE ACCESS TO THE INFORMATION BEFORE. AND HOW IT SHOULD BE ONGOING PROCESS OF EDUCATION. BUT WHEN IT COMES DOWN TO THE RESEARCH REGULATIONS AND FINDING A REGULATORY PATHWAY THROUGH THIS THAT SATISFIES 116 OR WHATEVER, IT WILL COME DOWN TO CONSENT 2. THAT'S WHAT I'M HEARING. THE ALTERNATIVE IS TO BE ACTUALLY TO REQUIRE SOMETHING MORE RESTRICTIVE THAN IS CURRENTLY GOES ON. IF WE HAVE TO, WE CAN DO THAT. IF THAT IS THE ONLY WAY TO SATISFY REGULATIONS BUT IF WE CAN FIND A WAY TO MAKE CONSENT TO CARRY BURDEN OF REGULATORY COMPLIANCE THEN WE HAVE MUCH MORE FREEDOM TO ALLOW CLINICIANS TO APPROPRIATELY HAVE THE CONVERSATIONS AHEAD OF TIME. SO WHAT TO PEOPLE -- DO PEOPLE THINK ABOUT THAT? >> I THINK I'M SPEAKING TO THAT. I WAS GOING TO SAY THAT I LIKE THE COMMENT BECAUSE WHEN I WAS LISTENING TO THE CONVERSATION IT SEEMED TO ME THAT THIS QUOTE INITIAL CONVERSATION IS MORE CONVERSATIONS. AND I ALSO WOULD SAY THAT THERE MIGHT BE SITUATIONS WHERE YOU MAY NOT EVEN HAVE NECESSARILY A MEANINGFUL INITIAL CONVERSATION, MIGHT BE SO HIGH-LEVEL THAT YOU ARE BASICALLY MENTIONING SOMETHING VERY BRIEFLY. THAT YOU MAY -- THERE MIGHT BE SITUATIONS WHERE YOU MIGHT ENCOUNTER A PATIENT THAT YOU HAVE TO MAKE A DECISION THEN AND THERE. ARE THERE CIRCUMSTANCES WHERE YOU WOULD NOT HAVE HAD MORE ROBUST CONVERSATIONS THEN JUST APPROACH SOMEONE OR IS IT NORMALLY A SERIES, THAT KIND OF THING, I WANT CLARITY ON THAT. >> I WOULD SAY THE VAST MAJORITY IS SERIES, VERY, VERY SMALL MINORITY, IS VERY, VERY CONTRACTED. EVEN PEOPLE WHO PRESENT VERY ILL. IT TAKES SOME TIME HOURS TO FIGURE OUT T REASONABLE TO DO A TRANSPLANT ON THIS PATIENT MEDICALLY SOCIALLY. SO IT IS NEVER I MEET A PATIENT, 12 YEARS LATER THEY ARE IN THE OR WITH AN ORGAN. ALMOST NEVER. >> SEEMS LIKE THEN I LIKE THE APPROACH, THE ONE THING I WAS THINKING THIS IS SIMILAR TO PLANNED EMERGENCY RESEARCH IN A WAY. BUT THAT'S WHAT I WAS THINKING. >> GREAT SEGUE. >> SORRY, THAT WAS WHAT I WAS THINKING ABOUT AND IT SOUNDS LIKE IN THOSE CIRCUMSTANCES, IT'S VERY SIMILAR, NOT JUST STEP ONE AND STEP TWO, IT'S ACTUALLY LOTS OF THINGS ARE HAPPENING ALONG THE WAY WITH COMMUNITY ENGAGEMENT AND VARIETY OF THINGS. THERE ARE PROBABLY MORE OPPORTUNITIES IN THIS SPACE TO WORK WITH INDIVIDUALS AS WELL. SEEMS LIKE WE CAN DO MORE IN TERMS OF INFORMING INDIVIDUALS THAN WE CAN IN THAT SCENARIO. THAT WAS MY ONLY COMMENT. >> MY QUESTION IS, AT WHAT POINT DOES A PATIENT IS A PATIENT LIKELY TO MAKE A DECISION, THAT CHANGES THE PROBABILITY THAT THEY WILL BE OFFERED AN ORGAN? WHAT I'M HEARING IS THAT IN THIS INITIAL CONVERSATION THEY MIGHT BE ASKED WHETHER THEY WOULD BE WILLING TO ACCEPT SOME SORT OF LESS THAN PERFECT ORGAN. IF THEY SAID NO, THEN THEY MIGHT NOT BE OFFERED AN ORGAN. IS THAT TRUE. IF NOT, AT WHAT POINT DO THEY MAKE THAT LIMITING DECISION, THAT CHANGES THEIR PROBABILITY, IT DOESN'T TOTALLY DETERMINE FROM WHAT I HEAR YOU SAY, THERE ARE PROBABILITIES IF YOU THOUGHT THEY WERE IN EXTREME SITUATION AND THERE WAS A COMPROMISE ORGAN YOU MIGHT OFFER IT TO THEM ANYWAY. BUT WHEN DO THEY MAKE A DECISION THAT CHANGES THEIR PROBABILITIES OF BEING OFFERED AN ORGAN? >> I THINK THE TIME FRAME AS WE WERE DISCUSSING GOES FROM A DAY OR TWO FOR SOME PEOPLE ALL THE WAY TO A DECADE. SO I THINK WE GENERALLY DO OUR BEST TO GIVE PEOPLE MULTIPLE OPPORTUNITIES TO REVISIT THESE ISSUES. MOST GO FROM MORE RESTRICTIVE TO LESS RESTRICTIVE AS THEY WANT MORE ORGANS BUT SOME PEOPLE NEVER CHANGE THEIR MINDS SO USUALLY, USUALLY THERE IS AN OPPORTUNITY OVER A PERIOD OF TIME AS THEIR CONDITION CHANGES TO REVISIT THESE DISCUSSIONS T. BUT I DON'T -- I THINK THE CHALLENGE IN TRANSPLANT IS EVERY PATIENT HAS A DIFFERENT TRAJECTORY. SO WE HAVE TO MAKE RECOMMENDATIONS THAT CAN FIT AND BE ADJUSTED TO THOSE TRAJECTORIES. >> FOLLOW-UP, IS IT POSSIBLE IN THAT INITIAL CONVERSATION YOU HAVE WITH A PATIENT, THE FIRST TIME YOU RAISED QUESTION OF TRANSPLANT, THEY COULD EXPRESS SOMETHING THAT WOULD START -- WOULD HAVE CHANGED PROBABILITIES THEY WOULD HAVE BEEN OFFERED AN ORGAN? >> SURE, YES. SOME -- >> IMPORTANT CONVERSATIONS. >> SOME PEOPLE ARE BLACK AND WHITE. THEY DON'T WANT INCREASE RISK ORGANS OF ANY FLAVOR. THEY EVEN CARE ABOUT THINGS WE DON'T EVEN CONSIDER INCREASE RISK IS INCREASED RISK. BUT VERY FEW PATIENTS REALLY START DRYING THOSE LINES DRAWING THOSE LINES IN THE SAND. THE LAST THING I WOULD SAY IS, WE DISCUSSED THIS ON THE THE LAST TIME WE WERE HERE, THE MOST DAMAGING TIME FOR PEOPLE TO CHANGE THEIR MIND IS FOR PEOPLE TO SAY YES THEN WHEN THEY SHOW UP IN THE HOSPITAL THEN SAY NO. BECAUSE THEN IT SENDS THIS ORGAN INTO A PURGATORY WHICH THEY MAY NEVER GET BACK INTO A PERSON. THIS CHANGING OF THE MIND IS SOMETHING THAT IS HUMAN, WE ACCOMMODATE THAT WITHIN THE TRANSPLANT PLAN BUT THE MOST DAMAGING TIME TO BE HONEST TO THE SYSTEM IS AT THE LAST MINUTE AND WE DON'T -- WE TRY TO EDUCATE PEOPLE TO MAXIMIZE THEIR OPPORTUNITIES. >> BOB WALSH FROM HRSA. TO BUILD UPON THAT IS ONE IMPORTANT FACT, SANDY IS CORRECT, OCCASIONALLY A PATIENT WILL ABSOLUTELY SAY I REFUSE, I WILL NEVER TAKE AN ORGAN FROM A HEP C DONOR OR SOME OTHER FACTOR, IS IT POSSIBLE THE SYSTEM IS BUILT SO THAT YOU CAN PUT IN CRITERIA FOR INDIVIDUAL PATIENTS OR CRITERIA FOR EACH TRANSPLANT CENTER SO THAT IF YOU REFUSE, YOU DON'T WANT TO RECEIVE OFFERS OF THAT TYPE, IT WILL SKIP OVER THAT PATIENT. FOR EFFICIENCY PURPOSES BECAUSE YOU DON'T WANT TO JUST BE -- IF THEY HAVE LIKE ADAMANTLY DEFINITIVELY SAY THEY WILL NOT TAKE THAT ORGAN, IT DOESN'T MAKE SENSE TO BE SLOWING DOWN GIVING TO SOMEBODY WHOLE TAKE THAT OFFER. IN THE VAST MAJORITY OF CASES THE PATIENTS ARE COUNCILLED TO KEEP THEIR COUNSELED TO KEEP THEIR OPTIONS OPEN BECAUSE CIRCUMSTANCES CHANGE AND IT'S ALSO IMPORTANT TO NOTE IF YOU PUT IN ONE OF THOSE CRITERIA IN THE SYSTEM THAT ROLES YOU OUT, THANK -- THEY CAN CHANGE. YOU ARE NOT SET IN STONE LISTED TO TRANSPLANT. >> WE HAVE BEEN TAKEN BY SIMILARITIES BETWEEN DDIR AND THESE OTHER HIGHER RISK CATEGORIES. IS THAT RIGHT? THERE ARE TWO PERSPECTIVES. THIS SOUNDS LIKE A DEEPLY CLINICAL DECISION MAKING PROCESS THROUGHOUT AND IN FACT WE ARE ALSO THE INVESTIGATORS ON THE STUDIES ARE UNLUKELY TO BE ANYWHERE NEAR THE PATIENTS ARE NOT GOING TO BE THE PEOPLE HAVING CONSENT, THE SURGEON WHOSE ARE MAKING THE DECISIONS A TT MOMENT MAY NOT KNOW ABOUT THE RESEARCH, SO THE SURGEONS AN TRANSPLANT TEAMS ARE MAKING COMPLETELY CLINICAL DECISIONS. IS THAT HOW YOU SEE THIS KIND OF RESEARCH GOING ON TOO? THERE ARE TWO THINGS. WE MAY SAY I'M SORRY YOU CAN'T DO THAT, THIS IS RESEARCH AND THERE'S NO WAY THROUGH THE REGULATIONS, YOU HAVE TO DO IT THROUGH A DIFFERENT PROCESS. BUT WE WERE STRUCK AT THE SORT OF TWO STEP I'LL CALL IT THAT FOR BETTER WORD, MULTI-STATE PROCESS FOR HIGH RISK AND HOW THAT SEEMED SIMILAR TO WHAT WE WANT TO DO. SO IS THAT -- SO SHOULD WE BASICALLY TRY TO SATISFY THIS UNDER THAT CRITERIA OR IS RESEARCH DIFFERENT FROM YOUR PERSPECTIVE FROM THE BEGINNING? >> WELL I THINK RESEARCH IS DIFFERENT BECAUSE I THINK THERE'S A LOT MORE UNKNOWNS. WE CAN PUT OUR ARMS AROUND RISK OF DISEASE TRANSMISSION. WE CAN PUT OUR ARMS BASED ON DATA, AND I THINK RESEARCH BY ITS NATURE AND THAT I THINK IS THE RISK LEVEL OF THE RESEARCH INTERVENTION THAT HAPPENED IN THE DONOR, THERE'S A LOT MORE UNKNOWNS. I THINK IT'S ALSO VERY DIFFICULT TO HAVE A RISK BENEFITS AND ALTERNATIVES DISCUSSION BECAUSE IF YOU ACCEPT THIS ORGAN THEN WE HAVE THESE UNKNOWN RISKS OF THE RESEARCH AND WHATEVER ELSE WE WANT TO DISCUSS. IF YOU DON'T ACCEPT THE ORGAN, THE ALTERNATIVES OF NOT ACCEPTING THE ORGAN IS WAY MORE UNKNOWN RELATIVE COMPARED TO ALTERNATIVES WHERE YOU HAVE A STANDARD OF CARE. IN THE STANDARD RESEARCH FORMULATION THE ALTERNATIVES ARE KIND OF KNOWN BECAUSE IT IS WHAT YOU WOULD DO WITHOUT THE RESEARCH. HERE WE DON'T KNOW WHEN THE NEXT OFFER IS COMING, WE DON'T KNOW FLAVOR OF ORGAN THAT IS, WE DON'T KNOW IF IT'S BROWN ONE OR GREEN ONE OR PURPLE ONE. SO THE ALTERNATIVES DISCUSSION IS DIFFICULT. NOW, THE ONLY THING I WOULD SAY IS THAT ONE OF THE REASONS WE FOCUSED A LOT AHEAD OF TIME ON EMPHASIZING HAVING THIS SINGLE REVIEW BOARD IRB FUNCTION IS THAT WE HAVE TO CONTROL OR AT LEAST HAVE A VERY CLEAR VIEW AS TO WHAT IS SCIENTIFICALLY MERITORIOUS TO EVEN ENTER THIS ZONE OF DDIR. AND THAT THAT IS WHERE THE BEST WAY WE CAN ASSESS, THE RISK THAT THE RESEARCH POSES TO THE ORGAN AND TO THE RECIPIENT OF THAT ORGAN, IS THAT FRONT END REVIEWING THE ANIMAL DATA, REVIEW -- THE USUAL SCIENTIFIC MERIT EQUIPOISE AND SO I THINK THAT'S WHY WE FELT THAT THIS OVERSIGHT COMMITTEE WAS IMPORTANT AS PART OF THESE DISCUSSIONS. BECAUSE IT'S NOT THAT ANYTHING IS GOING TO GET INTO THE ORGAN POOL, IT'S REVIEWED AND APPROVED AND APPROPRIATE AND ALL THAT STUFF HAS TO HAPPEN LEADING UP TO BEING OFFERED THIS SITUATION. SO MY -- >> THIS IS A GREAT DISCUSSION. MY SENSE IS THAT THIS FIRST CONVERSATION OR WHATEVER YOU WANT TO CALL IT IS NOT NECESSARILY STANDARDIZED. THERE'S A LOT ONE COULD SAY ABOUT BEST PRACTICES AND WHAT ONE WOULD IDEALLY LIKE TO SEE HAPPEN AT THIS TIME. BUT ITs NOT A REGULATORY PROCESS. WAIT ONE SECOND. I SEE. SO WHAT I WOULD REALLY LIKE TO DO IS TAKE THAT -- BECAUSE WE HAVE TIME TO KEEP TALKING ABOUT THIS, IT'S JUST I WANT INPUT FROM THIS COMMITTEE ON THE SECOND -- WHAT I THINK IS THE TIME FOR CONSENT AND SECRETARIAL WAIVER AND HOW WE FRAME THAT AND I WANT US TO HAVE TIME TO TALK ABOUT PLANNED EMERGENCY RESEARCH REGULATIONS AND HOW THAT FITS WITH ANY DDI RESEARCH REGULATED BY FDA. SO I WAS HOPING TO MOVE US INTO AFTER THE PERSON'S BEEN IDENTIFIED AS NEEDING A TRANSPLANT, THAT WHAT SE REFERRED TO AS THE SECOND CONVERSATION OR THE SECOND CONSENT OR IF WE PUT AWAY THE WORDS FIRST AND SECOND, THE CONSENT PROCESS. BUT YOU HAD A COMMENT. GO AHEAD. >> I MEANT TO MENTION EARLIER IN RESPONSE TO YOUR ORIGINAL QUESTION, AND YOU ARE EXACTLY RIGHT, IT IS NOT A STANDARDIZED PROCESS FOR THAT INITIAL CONVERSATION. HOWEVER, THERE IS SOME REQUIREMENTS. OPTN POLICY AND THE MEDICARE CONDITIONS FOR PARTICIPATION FOR TRANSPLANT CENTERS HAVE SOME REQUIREMENTS ON INFORMATION THAT MUST BE SHARED WITH PATIENTS AT THE TIME OF LISTING, INCLUDNG INFORMATION ABOUT THE POSSIBILITY OF RECEIVING INCREASE RISK ORGAN AND THOSE SORTS OF THINGS. THAT DOESN'T MEAN IT IS SAID IN THE SAME WORDS OR EXACTLY THE SAME WAY AT EVERY CENTER BUT THERE IS SOME REGULATORY AND POLICY REQUIREMENTS ON WHAT IT SHOULD BE INCLUDED IN THAT INITIAL DISCUSSION. >> OKAY. >> SO I'M TRYING TO TIE IT TOGETHER TO DISPARATE PIECES OF INFORMATION. I WAS THINKING WHAT CONSUELO SAID. I WENT THROUGH AND STRETCHED THE WORD RECIPIENT IN OUR DOCUMENT AND THERE IS NO REFERENCE TO THE CAPABILITY OF ANY PARTICULAR RECIPIENT TO UNDERSTAND INFORMATION IN ANY PARTICULAR FORM. IN REALITY, IT VARIES A LOT. WHEN CANCER PATIENTS ARE INFORMED ABOUT THINGS, SOME PEOPLE RESPOND BETTER TO WRITTEN, SOME PEOPLE RESPOND BETTER TO VERBAL, SOME PEOPLE NEEDED TO COME FROM SOMEONE THAT LOOKS LIKE THEM OR SOMEBODY WHO HAS A SIMILAR BACKGROUND. SO WE DON'T NECESSARILY HAVE TO MAKE THIS ONE FLAVOR. BUT GIVEN THAT THERE'S ALREADY MULTIPLE POINTS WHEN THE MEDICAL SYSTEM INTERACTS WITH THESE PATIENTS TO EXPLAIN THEIR RISK, WE CAN DESIGN THE SYSTEM THAT PROVIDES VARIOUS PLACES FOR PEOPLE TO GET INFORMATION. THE REALITY IS WHEN A MEDICAL PROCEDURE IS NEW, THAT THE FIRST ADOPTERS TEND TO BE PEOPLE WHO BE ABLE TO UNDERSTAND WHAT'S GOING ON AND GET THEMSELVES TO WHERE TRIAL MIGHT BE. WE ARE STRUGGLE WITH THIS RIGHT NOW IN TARGETED THERAPIES. MY PARTICULAR POPULATION OF CANCER IS 1% OF NON-SMALL CELL LUNG CANCER PATIENTS. AND WE HAVE -- TESTING FOR IT, IT'S INFORMED PATIENTS GETTING THEMSELVES TESTED, HOPEFULLY EVENTUALLY WE WILL GET THE STANDARDIZED SO IT'S MORE AVAILABLE HE CAN TABLY TO ICTBLY TO EVERYBODY. BUT YOU START OUT SOMEWHERE. SOY THINK IF WE WANT TO GET THIS ROLLING THAT MIGHT START WITH KIND OF A TEST SYSTEM WITH THE INFORMATION IS AVAILABLE ON THE WEB AND GRANTED THAT'S NOT GOING THEY'RE MAKING INFORMED CONSENT. >> SO I WOULD PROPOSE WE LOOK AT THE SECOND SCENARIO. BECAUSE IF WE CAN SATISFY OURSELVES THAT IT'S ETHICAL, TO CONDUCT WE CAN OFF LOAD TO PRIOR CONVERSATIONS AND I WILL HAVE TO BE SOMETHING LIKE I THINK WE WANT TO AVOID SIMPLY HAVING A RULE THAT SAYS >> IT'S GOING TO END UP BEING. IF WORE CHALLENGE AND WE CAN START OFF LOADING IT I DON'T WANT TO BE PRESCRIPTIVE ABOUT THE PARTICULAR WAYS OF DOING THAT. BUT I THINK WE'LL END UP HAVING TO SAY SOME OF THESE H HAVE TO BE DISCUSSED AND DOCUMENTED BEFORE, WALTER THEN SKIP. >> SO IS IT MORE I THINK ABOUT IT THE MORE I I'M TROUBLED BY THE TWO STEP PROCESS. THE EXAMPLE PROVIDED EARLIER, WHEN YOU ARE ON A DIALYSIS FOR EIGHT YEARS YOUR SENSE OF DIALYSIS, WHAT IT MEANS FOR YOUR LIFESTYLE, IS VERY DIFFERENT WHEN YOU ARE STARTING I I DIALYSIS THAN FIVE YEARS DOWN THE ROAD SO IT UNDERSCORES AN ONGOING SET OF I DIALOGUES WITH PATIENTS BECAUSE THEIR TOLERANCE AND SENSE OF WILLINGNESS FOR A ORGAN EXTENDED CRITERIA ORGAN MAY BE DIFFERENT FIVER YEARS INTO DIALYSIS THAN DAY ONE SO IT'S SORT OF UNDERSCORES TO MY MIND THE VALUE OF AND IMPORTANCE OF ONGOING DISCUSSIONS AND PRESSURE TESTING THE PATIENTS INTEREST IN SUCH WAYS. >> I FIND MYSELF CONFUSED BY YOUR COMMENTS. I DON'T WANT TO TRY TO ARTICULATE WHY -- I WANT TO ARTICULATE WHY. THAT FIRST CONVERSATION IS NOT A RESEARCH CONSENT CONVERSATION. WE CAN AGREE IT'S A E LISSATION OF PREFERENCES, FIRST STEP OF SOME EDUCATIONAL PROCESS. WE CAN ALSO SAY IT WOULD BE IDEAL BETWEEN THAT DAY AND THE DAY YOU ARE OFFERED AN ORGAN TO LEARN AS MUCH ADS POSSIBLE ABOUT WHAT'S GOING TO HAPPEN. BUT I DON'T THINK WE CAN NECESSARILY SAY THAT THAT WOULD HAVE HAPPENED IN EVERY CASE. IT'S -- GIVEN ALL THE VARIABILITIES, ALL THE DIFFICULTIES, THE TIMING ISSUES, THE LOCATION, ALL OF THE ISSUE -- I DON'T THINK WE CAN ASSUME AND PRESPECIFY THAT TAKES PLACE SO I'M LEFT WITH THE DEFAULT OF SAYING THAT THAT SECOND CONVERSATION IS THE RESEARCH CONSENT AND ON THE ASSUMPTION THEY MAY NOT HAVE TAKEN PLATE, IT'S THE LOWEST COMMON DENOMINATOR WHICH IN MY MIND IS SECRETARY OF WAIVER. I DON'T THINK WE CAN PREDICATE WHAT GOES ON IN THE SECOND ONE TO ASSUMPTION WHAT MAY OR MAY NOT HAPPEN BETWEEN STEP ONE AND THE TWO. >> I THINK WE SHOULD TRY TO FIND A WAY TO MAKE WHETHER IT'S -- THAT WAS WHY I MADE THE DISTINCTION BETWEEN ETHICS AND REGULATION. I THINK WE COULD SAY TODAY THERE'S A SECRETARY WARE THIS FITS UNDER 5024, YOU CAN DO IT. I THINK WE HAVE TO DECIDE WHETHER WE'RE COMFORTABLE WITH THIS BEING AN ETHICAL SITUATION. IF WE ARE WHATEVER MECHANISM WE HAVE AT HAND. IF WE DON'T WE HAVE THE THINK ABOUT OTHER THINGS. >> IF WE'RE IN AGREEMENT WE NEED TO BE CAREFUL USING WORDS VERSUS SHOULD, VERSUS WILL, THAT WILL BE IDEAL AND ETHICAL, WOULD ARE WILL MEANS REQUIRED BY REGULATION IN ORDER TO HAVE THAT SECOND BE IMPLEMENTED. SO WE JUST NEED TO BE -- MAYBE THAT'S AS YOU HAVE DESCRIBED, SOMETIMES I HAVE INTERPRETED SOME OF YOUR COMMENTS ABOUT THAT IN BETWEEN PROCESS AS BEING A REQUIREMENT. AS OPPOSEDDED TO IDEALLY ETHICALLY OPPOSED TO REGULATORY REQUIREMENT FOR NUMBER TWO. >> I THINK IF WE -- I WILL TRY TO USE AS STRAIGHT FORWARD TERMS BUT I THINK WE'RE IN AGREEMENT. THE IDEAL CIRCUMSTANCE IS IF WE FIND IT ETHICAL TO DO SO THAT WE FIND A WAY TO FIT THE REGULATIONS TO THE SECOND -- TO THE SECOND CONSENT BEING RESEARCH CONSENT. THE OTHER OPTIONS WERE I DON'T WANT PEOPLE TO GO INTO THIS FEELING THAT'S THE ONLY WAY. IF WE ARE NOT -- IF WE DON'T FEEL IT'S ETHICAL WAY TO TREAT PEOPLE, THEN WE SHOULD THINK ABOUT WE SHOULD UNDER THOSE CIRCUMSTANCES THINK ABOUT WHAT WE -- THE MINIMAL THINGS WE NED TO OFF LOAD TO -- NEED TO OFF LOAD TO EARLIER CONVERSATIONS. THAT'S ALL. >> ONE THING I WOULD LIKE TO PROPOSE AS A KNOW MEN NOMENCLATURE, IT SOUNDS LIKE THERE'S AN INITIAL CONVERSATION AND ORGAN OFFER CONVERSATION. THOSE TWO WE KNOW EXIST. SOMETHING MAY OR MAY NOT HAPPEN IN BETWEEN BUT THOSE ARE THE TWO THAT WE KNOW EXIST. AND IS IT POSSIBLE TO HAVE ANY SENSE IN ADVANCE OF WHO IS IN A SITUATION WHERE THERE ARE LIKELY TO BE OFFERED RESEARCH OR -- RESEARCH ORGAN OF THIS KIND? IS ANYONE EQUALLY LIKELY TO DO THAT? OR DO THEY NEED TO BE ASSOCIATED WITH A PARTICULAR CENTER OR CERTAIN KIND OF CENTER, IS THERE ANY WAY TO HONE IN ON WHO IS LIKELY TO VET THIS KIND OF OFFER? >> NO. ORGANS ARE SHARED NATIONALLY, SO IT'S NOT A LOCATION ISSUE. I THINK THE ONLY THING I WOULD SAY IS THESE INTERVENTIONS ARE MORE LIKELY TO BE CONDUCTED ON NON-IDEAL DONORS. IF YOU HAVE AN IDEAL DONOR THERE'S NOT MUCH MOTIVATION TO BE IMPROVING QUOTE UNQUOTE DONE. SO THERE ARE -- SO THIS WOULD GENERALLY BE THE OLDER DONOR OR THE DONOR WITH MEDICAL CO-MORBIDITIES. BUT THE PROBLEM IS WHILE MAYBE IN KIDNEY, THAT WOULD BE DIRECTED BECAUSE OF THE WAY ALLOCATION IS ORGANIZED, THE IDEAL ORGANS ARE DIRECTED TOWARDS ONE SET OF PATIENTS AND SOME PATIENTS DON'T ACTUALLY HAVE ACCESS TO THE IDEAL ORGANS BECAUSE OF THE WAY ALLOCATION OR HAVE MUCH, MUCH REDUCED ACCESS, THIS IS EVERY WHICH WAY FOR EVERY WHICH ORGAN SO I THINK THIS IS ANOTHER CHALLENGE, THERE'S NO WAY TO NARROW THE POOL OF POTENTIAL PEOPLE THAT ARE AFFECTED. >> LAKELY RECIPIENTS -- LIKELY RECIPIENTS. >> CORRECT. >> CAN I JUST MAKE ONE COMMENT. JOHN FROM FDA. >> SPEAK UP. >> (OFF MIC) FROM A DEVICE -- TRANSPLANTATION STANDPOINT, I DON'T THINK IT'S SAFE FOR US TO VIEW THE RESOURCES ONLY ON WHAT NEED WE BELIEVE MIGHT BE NON-IDEAL EXTENDED CRITERIA ORGANS. WE CERTAINLY ALREADY HAVE EXPERIENCE WHERE STUDIES HAVEN'T ON DONORS HAVE INVOLVED WHAT ARE PRESUMED TO BE STANDARD DONORS. SO ANYTHING THAT WE DO IN TERMS OF MODIFYING THE CONSENT PROCESSES FOR RESEARCH, IS IN ALL LIKELIHOOD GOING TO GET EXPANDED TO PERHAPS ALL DONORS NOT JUST SUBOPTIMAL DONORS, HIGHER RISK DONORS. MAYBE WE SHOULD HOLD THOSE UP AND START TO TALK ABOUT IN WHAT WAYS WE ARE COMFORTABLE WITH A PROCESS AT THE TIME OF ORGAN OFFER, THAT COULD SATISFY THOSE OR WHERE THEY WOULD NEED TO BE MODIFIED AND ONCE WE GET MODIFICATIONS WE NEED WE CAN DECIDE WHETHER THAT'S TOO FAR OR NOT. >> THANKS, DAVID. COUPLE OF VIEWS. LIKE I SAID STEVEN AND NANCY AND I HAVE BEEN WORKING ON THIS. SO STEVEN HAS PROPOSED THAT WHAT WE ARE REALLY WAIVING IS THE OPPORTUNITY TO CONSIDER -- OPPORTUNITY TO CONSIDER PARTICIPATION IN THE RESEARCH. NANCY HAS PROPOSED -- FORGIVE ME IF I MISSTATE YOUR POSITIONS. NANCY HAS PROPOSED TO DO A WAIVER BUT WE NEED TO HAVE KEY INFORMATION SO THAT EVERYBODY HAS A SENSE AT LEAST A LITTLE BIT OF A SENSE, SNAP SHOT OF THE FACT THAT THEY ARE BEING ASKED TO PARTICIPATE IN RESEARCH. AND I'M JUST A LITTLE CONFUSED WHICH COULD BE BECAUSE I'M GETTING OLDER AND THAT HAPPENS TO ME BECAUSE I'M TRYING TO PUT MYSELF IN THE SHOES OF A SURGEO ACTUALLY WHO IS NOT GOING TO BE THE INVESTIGATOR WHO DID THE RESEARCH WHO NEEDS TO UNDERSTAND WHAT'S THE CONVERSATION THAT SURGEON NEEDS TO HAVE WITH RESPECT TO THE ORGAN WHICH THERE WAS RESEARCH CONDUCTED. WHAT ARE WE ACTUALLY WAIVING, DOES THIS PERSON NEED TO DISCUSS RISKS, BENEFITS, ALTERNATIVES? I DON'T KNOW. BUT I'M JUST SAYING THAT I THINK WE NEED TO HAVE A CONVERSATION ABOUT WHAT ARE THE DIFFERENT WAYS TO APPROACH THIS AS PRECISE THE OHRP QUESTION, WHAT WOULD BE THE SCOPE OF THE SECRETARY YAL WAIVER. >> LET ME SPEAK TO MY PERSPECTIVE. I DIDN'T THINK THERE WAS ANY REASON TO WAIVE ANY OF THE REQUIRED ELEMENTS OF THE INFORMED CONSENT DOCUMENT. I THINK INFORMED CONSENT ARE USED AT TIME OF CONSENT, THEY ARE USED AFTERWARDS. THERE'S NO REASON TO TAKE THAT AWAY. UNDER THE NEW RULE THERE HAS TO BE A KEY INFORMATION SECTION AT THE BEGINNING WHICH IS ONE OR TWO PAGES. HOPEFULLY MAYBE LONGER BUT AT LEAST SOMETHING THAT'S SUPPOSED TO BE MORE IMMEDIATELY MEANINGFUL. WHAT I THINK CAN'T HAPPEN REALISTICALLY FOR SO MANY REASONS, NOT -- TIME IS THE OBVIOUS ONE, BUT ALSO PEOPLE ARE FACING WHAT THEY ARE LIKELY TO SEE AS LIFE AND DEATH DECISION. THEY'RE OFFERED AN ORGAN THAT WILL -- THAT'S WHAT THEY ARE WAITING FOR. IT'S NOT A SIMPLE SITUATION WHICH PEOPLE CAN SIT THERE AND THINK ABOUT AND TAKE CONSENT HOME AND DISCUSS WITH THEIR FAMILY. SO TO ME THE THING WE HAVE TO RECOGNIZE IS NOT HAPPENING IS 116A 2, AN INVESTIGATOR SHALL SEEK INFORMED CONSENT UNDER CIRCUMSTANCES TO PROVIDE PERSPECTIVE SUBJECT OR L AR WITH SUFFICIENT OPPORTUNITY TO DISCUSS AND CONSIDER WHETHER OR NOT TO PARTICIPATE. I THINK THAT'S A GIVEN, THAT IS NOT HAPPENING UNDER THIS CIRCUMSTANCE. SO TO ME, THAT'S THE MOST CRITICAL THING WE HAVE TO RECOGNIZE. AND I THINK THIS IS STILL FOR ALL THE REASONS WE HAVE DISCUSSED, DISCUSSED IN THE NAM REPORT, THIS IS REALLY IMPORTANT RESEARCH TO BE DONE. IT WILL IN THE END INCREASE THE NUMBER OF ORGANS OF IDEALLY INCREASE NUMBER OF ORGANS AVAILABLE TO ALL. THE RISK LEVELS ARE RELATIVELY LOW IN THE CONTEXT OF WHAT ELSE IS GOING ON. I THINK IT IS ETHICAL BUT I DON'T -- IT'S DISINGENUOUS TO SUGGEST ANY OTHER FORMULATION IS GOING TO SATISFY A 2 UNDER THESE SIXER. THEY ARE -- CIRCUMSTANCES. THERE'S SPECIAL CIRCUMSTANCES PEOPLE ARE NOT CONFIDENT AND OTHER THINGS BUT IN GENERAL THAT'S MY CONCERN. >> I WANTED TO INSERT A THOUGHT THAT THIS OFFER IS COMING WHEN A PERSON IS LYING IN BED AT 2 IN THE MORNING. THERE'S NO PIECES OF PAPER, THERE'S A COORDINATOR ON THE PHONE, THERE MAYBE A TRANSLATOR THROUGH WHICH -- THIS ISN'T THE STANDARD VIEW OF A PERSON SITTING IN AN OFFICE OR SITTING IN A HOSPITAL BED DEALING WITH AN INFORMED CONSENT. >> I WAS GOING TO ASK FOR THAT, I MEAN PUTTING THE DOCUMENT ASIDE DECIDING WHICH GET WAIVED OR NOT, A WAIVE OF INFORMED CONSENT EXCEPTION EMERGENCY RESEARCH STILL HAS A DOCUMENT, EVEN IF YOU ARE WAIVING TALKING TO THEM AT ALL. I DON'T THINK WE START PARSING IT TO SAY WE'RE WAIVING THIS TOO AND NOT 4 AND NOT 8. WE CAN GET INTO THAT BUT WHAT YOU WILL LIKE TO HEAR IS MORE ABOUT WHAT TAKES PLACE. IF I'M LYING IN BED AT HOME, I GET A CALL AT 3 IN THE MORNING, HOW MUCH TIME IS SPENT IN THAT CONVERSATION AND WHAT IS IT THAT YOU SAY? I WOULD LIKE TO HEAR THAT. I MEAN -- >> THE SHORT VERSION IS WHAT EVERYTHING IS AVERAGE, YOU JUST SAY WE HAVE THIS ORGAN, IT'S FROM A PERSON IN THEIR 40s. WE THINK THIS IS -- THE LONGER VERSION IS WHEN YOU HAVE THINGS THAT ARE NOT THE QUOTE UNQUOTE AVERAGE IN STANDARD. THEN WE HAVE OUR COORDINATORS DO HAVE CERTAIN SCRIPTS THAT THEY FOLLOW WHEN THEY ARE TALKING ABOUT AN ORGAN THAT HAS AN INCREASE RISK OF NOT WORKING, VERSUS DISEASE TRANSMISSION RISK AND THESE ARE THINGS PEOPLE HAVE HEARD OF BEFORE SO YOU THEN ASK THEM ARE YOU GOING WITH -- YOU INDICATE YOU ARE AGREEABLE AND YOU VERIFY THAT. SO THIS IS AGAIN, TYPICALLY A CONVERSATION THAT CAN BE TWO, THREE, FOUR MINUTES, AND SOMETIMES I HAVE CALLED THE SAME PATIENT THREE TIMES MYSELF TO GIVE ORGAN -- SO THERE IS A LOT OF VARIABILITY. AVERAGE THINGS ARE GENERALLY NOT DISCUSSED IN ANY DETAIL AND THE FOCUS IS TO TELL THEM ABOUT THINGS THAT ARE NOT THE STANDARD AND NOT AVERAGE AND THEN TO DEAL WITH ALL THE LOGISTICAL ISSUES OF WHAT THEY HAVE TO MANAGE. >> AND TO FOLLOW-UP. SO WE ARE LOOKING AT A FEW MINUTES, MAYBE FIVE, AND A SCRIPT. SO PRESUMABLY THERE COULD BE A SCRIPT FOR RESEARCH AND THE LIKES. HOW MUCH TIME DOES THE ORGAN PROCUREMENT AGENCY GIVE YOU AND THEREFORE YOU GIVE TO THE PATIENT, TO MAKE A DECISION WHERE THEY THEN WOULD MOVE ON. >> WE ARE GIVEN 60 MINUTES BUT YOU HAVE TO REALIZE IT CAN BE 30 MINUTE BFERS YOU EVEN FIND THE PATIENT. YOU ARE ALSO GIVEN 60 MINUTES AND SOMETIMES I HAVE TO TURN ON MY COMPUTER AND LOOK UP STUFF ABOUT THIS DONOR BECAUSE IT'S COMPLEX. THERE'S A LOT OF DIFFERENT THINGS YOU ARE GIVEN 0 MINUTE BUS IN A KIDNEY SITUATION MY COORDINATOR IS CALLED AND WE HAVE TO ACTIVELY CHECK WITH THIS PARTICULAR DONOR BASED ON THE MOST RECENT BLOOD TEST, IS THE COMPATIBILITY SO THE 60 MINUTES, IT CAN BE 30 TO 40 MINUTE BFERS YOU GET TALKING TO -- BEFORE YOU GET TALKING TO THE PATIENT. >> IS THERE A POINT ESTIMATE ALL AROUND HOW THAT TRANSLATES TO ME, I ONLY I'M HOME, HOW MUCH TIME DO I GET? >> THE VAST MAJORITY OF PATIENTS MOST PATIENTS WILL DECIDE 80% THEN THERE'S 20% THAT SAY GEE, I WANT YOU TO TALK TO MY WIFE, I WANT YOU -- I WANT TO TALK TO MY CHILDREN. SO THERE'S SOME PERCENTAGE THAT ASKS FOR MORE TIME BUT MOST PEOPLE TAKE IT OR LEAVE IT WHEN THEY GET PRESENTED THAT CALL IN A MINORITY WANT MORE TIME TO THINK ABOUT IT OR DO WHATEVER ELSE THEY NEED TO. >> WHAT IS THE MOST TIME YOU EVER GIVE ME IN GENERAL IN >> I WOULD GENERALLY SAY I WILL CALL YOU BACK IN ABOUT 15 MINUTES. AND THE 60 MINUTES IS OBVIOUSLY NOBODY IS GOING TO BE DRA DRACONIAN, THERE IS NO MINUTE TO SECOND TIME CLOCK. BUT YOU HAVE TO RESPECT THAT BECAUSE OTHERWISE EVERYTHING GRINDS TO HALT. IF THEY WANT MORE TIME I USUALLY SAY TEN TO 15 MINUTES. >> WE ARE IN A 15 MINUTES, 20, 25, AT BEST MAYBE 30 BUT USUALLY 15. OKAY. >> SO LET ME THROW THIS OUT. WHAT IF WHENEVER THERE'S A PROTOCOL APPROVE BID IRB -- APPROVED BY IRB THAT INVOLVES RESEARCH CONDUCTED ON AN ORGAN FROM A DISEASED DONOR, THERE'S A SHORT SUMMARY CREATED. THAT IS -- WOULD FIT THE REQUIREMENTS OF KEY INFORMATION PROVIDE THE BASIC CRITICAL INFORMATION. AND THAT WHEN SOMEBODY IS OFFERED AN ORGAN, THAT GIVEN THE TIME CONSTRAINTS AND EVERYTHING ELSE, THAT WE WAIVE COB SENT, WAIVE ALL ELEMENTS OF CONSENT EXCEPT THEY HAVE TO BE GIVEN THAT SUMMARY, LEGALLY AUTHORIZED REPRESENTATIVE AND THIF TO BE GIVEN THE LONG FORM RESEARCH INFORMED CONSENT. I THROW THIS OUT AS A STARTING POINT. >> SO MY SHE WOULD, -- MICHELLE WHAT DOES IT MEAN? WHEN WE TALK WAVERS WE ARE USED TO INFORMED CONSENT. >> YOU ARE JUST WAIVING INFORMED CONSENT. >> THESE PEOPLE EVEN IN EMERGENCY RESEARCH THERE'S COMMUNITY CONSULTATION AND STUFF BUT THOSE PEOPLE DON'T GET CONSENT. HERE WE ARE GETTING SOMETHING. WE CAN ARGUE WHETHER IT'S INFORMED CONSENT PER REGULATIONS BUT PEOPLE ARE MAKING A DECISION AND EXPRESSING THEIR CHOICE. THAT'S JUST THERE. THERE ARE OBVIOUSLY CIRCUMSTANCES WHERE THEY ARE INEX TENT AND ALL -- INCOMPETENT AND OTHER THINGS, THAT'S WHAT'S GOING ON SO IT HAS MADE ME UNCOMFORTABLE SAYING THIS IS A WAIVER OF CONSENT. >> I'M NOT SURE WE ARE GETTING CONSENT, WE ARE WAIVING CONSENT AND WHAT WE ARE TALKING ABOUT IS PROVIDING THEM WITH INFORMATION ABOUT THE RESEARCH THAT'S BEEN DONE ON THE ORGAN, BECAUSE IF THEY DON'T HAVE THE TIME TO -- AND THE SITUATION, THE CIRCUMSTANCES TO CONSIDER IT, WE ARE NOT GETTING THEIR CONSENT. >> BUT THEY CAN SAY NO. >> THEY CAN SAY NO. SURE. BUT -- OKAY. SKIP. >> NANCY. >> OKAY SO NOW I SORT OF UNDERSTAND SOME OF THE WHAT WE ARE DISAGREEING ABOUT, IT MIGHT NOT BE A REAL DISAGREEMENT. I REALLY APPRECIATE YOU ARE SAYING STEVEN WE ARE REALLY ONLY WAIVING THE TIME CONSIDERATION BUT IN PRACTICAL TERMS WHAT THAT MEANS ON THE GROUND IS YOU GENERATED A FORM LIKE YOU ALWAYS DO FOR 5024 BUT IF NOBODY EVER SEES IT OR GETS TO CONTEMPLATE IT THEN WE ARE ACTUALLY NOT GETTING -- THEN IT'S NOT AN INFORMED CONSENT. IF WE SAY OKAY, LET'S WAIVE THE FULL BLOWN THING BUT WE HAVE TO CREATE THE CONSENT FORM ANYWAY JUST IN CASE, AND ACTUALLY REQUIRE SOME WAY OF CONVEYING THE KEY INFORMATION SUMMARY MICHELE IS TALKING ABOUT, HERE IS THE REALLY SHORT SCRIPT OF WHAT YOU NEED TO KNOW ABOUT THIS OFFER OF AN ORGAN THAT'S HAD RESEARCH DONE ON IT, THEN WE ARE AT LEAST GETTING CLOSER TO SOMETHING THAT WE COULD SAY ACTUALLY SATISFIES THE REQUIREMENTS OF BELMONT. >> I THINK WE ARE IN AGREEMENT. THIS A WAIVER OF CONSENT. IF WE DO THAT PEOPLE WILL TAKE IT TO BE NOT THE PEOPLE AT THIS TABLE BUT THERE'S A SECRETARIAL WARE OF CONSENT FOR ORGAN DONATION. DDIR, THAT'S NOT QUITE THE RIGHT MESSAGE OUTSIDE OF A VERY SOPHISTICATED AUDIENCE THAT UNDERSTANDS EXACTLY WHAT WE ARE TALKING ABOUT. THAT IS WHY I WOULD HAVE THEM GO THROUGH ALL THIS STUFF, PREPARE THE LONG FORM, WHETHER YOU CALL IT SOMETHING ELSE, WHAT YOU ARE NOT ABLE TO DOTY COMPLETELY AGREE -- I COMPLETELY AGREE NOT CONSENT PER REGULATIONS, THE REASON I SEE IS BECAUSE OF A 2 BECAUSE YOU DON'T HAVE THE TIME. SO THAT WAS WHAT THAT'S MY ARGUMENT, IT DOESN'T CHANGE WHAT WE ARE DOING BUT IT CHANGES THE REGULATORY PATHWAY BECAUSE I'M SCARED OF SENDING THE SIGNAL THAT THIS RESEARCH IS DONE UNDER WAIVER OF CONSENT. THAT'S BASICALLY WHAT I -- >> WE HAVE TO TACKLE THAT REGULATORY QUESTION. I AGREE. I THINK WITH THIS COMMUNICATION IS HELPFUL BECAUSE EVEN IF EXCEPTION FROM INFORMED CONSENT WHERE YOU WAIVE IT, THERE'S AN OPPORTUNITY FOR OPT OUT SO YOU CAN SAY NO, IF SOMEONE IS STANDING THERE YOU CAN SAY NO. SO I COULD -- IF I'M APPROACHED SAY NO. THERE IS A DANGER, I SAY YES AND START UNPACKING MY LITTLE -- AND I START -- AND I DON'T KNOW WHEN I GET A COPY OF THE FORM, I CAN GET INTO THE HOSPITAL, IF HOME IS -- FAX IT TO ME OR EXMAIL IT TO ME. -- EMAIL IT TO ME. FROM A PRACTICAL MATTER UNLESS IT COULD GET EMAILED BUT I MA MAY NOT HAVE EMAIL SO ASSUME THAT I GET THEN THE SUMMARY AND THE FULL FORM WHEN I ARRIVE AT THE HOSPITAL, AN INTERESTING QUESTION TO ASK IF I START AND ACTUALLY LOOKING THROUGH THAT, WHETHER I'LL CHANGE MY MIND. HOPEFULLY THAT WILL NEVER HAPPEN. BUT WE CAN'T PREVENT THAT FROM EVER HAPPENING. SO THAT'S GOING TO BE A JUDGMENT CALL. SO THERE'S -- I CAN SAY NO AT THE BEGINNING THEN THE PRESUMPTION IS THAT I'M IN. BUT I CAN ALWAYS SAY NO ALL THE WAY UP TO THE TIME I GET ENROLLED INTO THE -- GETTING ROLLED INTO THE OPERATING ROOM. IDEALLY WE DON'T WANT THAT TO HAPPEN BECAUSE THAT ORGAN IS WASTED. I APPRECIATE THAT. SO I THINK THE PROBLEM IS WE ARE WAIVING CONSENT BUT THE CHALLENGE IS WE'RE NOT WAIVING COMMUNICATION. >> THAT'S THE ISSUE. >> AND I'M REMINDED OF A PROJECT BACK IN MY ACADEMIC LIFE WHERE WHEN I RAISE THE QUESTION OF WAIVING CONSENT WITH PARENTS FOR RESUSCITATION RESEARCH COOLING ET CETERA, THEIR FIRST REACTION WAS NO. WHY? BECAUSE THEY THOUGHT I WAS THEN NOT GOING TO TALK TO THEM. SO WHEN THEY UNDERSTOOD THAT I WAS WAIVING THIS REGULARLATORY REQUIREMENT YET I WAS GOING -- NOT I BUT INVESTIGATORS WOULD BE COMMUNICATING THE WHOLE TIME, WITH THEM AND THEY COULD ALWAYS SOME POINT STOP IT, BUT THE HIEM THERMIA HAD -- HYPOTHERMIA HAD TO BEGIN DURING RECESS STATION, THEN THEY SAY OKAY THAT'S DIFFERENT. SO I AGREE WITH THAT BUT NOT SURE THE REGULATORY PATHWAY CHANGES HOW WE COMMUNICATED UNDERSTAND IT, FRAME IT I THINK IS IMPORTANT. IT'S NOT CLEAR TO ME THAT WE CAN DO THIS WITHOUT A WAIVER OF CONSENT IN A REGULATORY SENSE AND WE DO WANT TO COMMUNICATE, WE ARE NOT WAIVING COMMUNICATION. >> ABSOLUTELY. WE HAVE ALREADY HAD MULTIPLE INSTANCES IN THIS MEETING ALONE WHETHER IT WAS ABOUT MINIMAL RISK OR ABOUT CONSENT OR RECONSENT WHERE WE HAVE BEEN REMINDED THAT WORDS MATTER. SO THAT'S WHAT I -- THESE -- WE ARE TALKING ABOUT PEOPLE ANYWHERE. WHO MAY HAVE SEEN WAIVER OF CONSENT IN CONTEXT OF OTHER THINGS WHERE IT MEANS YOU JUST MOVE AHEAD. SO THAT'S I THINK THE ONLY POINT -- SOMEONE BROUGHT THIS UP AT THE LAST MEETING, SOMEONE FROM THE TRANSPLANT COMMUNITY. WE CAN DO WHAT WE DO IN OTHER SITUATIONS WHERE PEOPLE ARE NOT GIVEN THE OPPORTUNITY TO GET REAL INFORMED CONSENT WHICH IS THIS IS A POPULATION THAT WILL BE IN THE HOSPITAL. YOU CAN SHARE THE DOCUMENT WITH THEM, THEY WILL PROBABLY BE LYING IN BED FOR A WHILE. THEY COULD OPT OUT AFTER THE FACT TO ANY SUBSEQUENT -- WHO KNOWS RESEARCH DATA COLLECTIONS WE WOULDN'T LIKE THAT, BUT IT WOULD SHOW RESPECT FOR AUTONOMY, HOPEFULLY THEY WOULDN'T DO IT. SO WE CAN SPECIFY THAT IN FRAMING OUR SOLUTION TO THE PROBLEM. >> THE SITUATION OF STAGE 4 CANCER PATIENTS GOING INTO CLINICAL TRIAL IS SIMILAR THAT OUR LIVES ARE OFTEN ON THE LINE. THE TIMES IIVES INVOLVED ON MY -- TIMES I HAVE BEEN INVOLVED IN MY OWN OR WITH OTHER PEOPLE THESE ARE ENGAGED PATIENT WHOSE DID RESEARCH AHEAD OF TIME AND TALKED TO OTHER PATIENTS ABOUT THE TRIAL. IT'S STILL THE HOUR THEY SET ASIDE TO TALK TO US ABOUT THIS CONSENT STILL LEAVES US WITH QUESTIONS UNANSWERED. I JUST DON'T SEE HOW YOU CAN USE THE CURRENT FORMAL CONSENT THAT TRIALS SPONSORS EXPECT TO HAVE THIS BIG LONG DOCUMENT AND EXPECT TO GIVE SOMEBODY INFORMED CONSENT UNDER THESE CONDITIONS. YOU HAVE TO HAVE GONE THROUGH THAT PROCESS OF INFORMING THEM AHEAD OF TIME. IT ISN'T ENOUGH FOR THEM -- ONCE THEY HAVE THE ORGAN IN THEM TO START TELLING THEM ABOUT IT. >> SO LET ME CHALLENGE THAT. WHAT I'M GOING THE CHALLENGE, WE ALL AGREE YOU CANNOT DO THIS AT THE TIME. AT THIS POINT IN THE CONVERSATION THAT'S A GIVEN. THE QUESTION IS CAN WE RELY -- IS IT UNETHICAL TO GO AHEAD WITH THE RESEARCH GIVEN IT BE REVIEWED BY THE DROC AND TRANSPLANT IRB WHICH IS FAMILIAR WITH THIS PARTICULARLY FAMILIAR WITH THIS, DO WE FEEL WE NEED TO HAVE HAD THAT CONVERSATION AHEAD OF TIME OR PUT ASIDE REGULATIONS FOR THE MOMENT THERE ARE WAYS AROUND THAT. WE WILL TALK ABOUT THAT BUT DO WE FEEL THAT'S DISRESPECTFUL VIOLATES AUTONOMY IS UNETHICAL TO ACTUALLY GO AHEAD WITH THIS -- PEOPLE SAYING FINE BUT YOU KNOW THEY DON'T REALLY UNDERSTAND WHAT THEY ARE GETTING INTO. >> YOU SAID WE COULDN'T ASSUME DROC EXISTED THAT THOSE THINGS WERE AVAILABLE. THAT'S THE PROBLEM I STATED AT THE VERY BEGINNING IS HOW WE GET INFORMATION TO PEOPLE. >> DROC TO ME IS A STAND IN FOR SCIENTIFIC REVIEW COMMITTEE THAT LOOKS AT IMPACT OF -- THAT REALLY IS VERSED IN THIS AND HAS LOOKED THE OTHER PIECE THAT WE HAVEN'T DISCUSSED IN PROBABLY OUT OF SCOPE IS IMPACT OF THIS RESEARCH ON OTHER AVAILABLE ORGANS TO OTHER PEOPLE WHICH HAS TO BE TAKEN INTO CONSIDERATION IN THE SCIENTIFIC DISCUSSION. I THINK DROC, THAT SEEMS LIKE IT WOULD SIT THERE. BUT I THINK WE HAVE TO ASSUME THAT WHETHER IT'S DROC OR THE SPECIALIZED IRB OR AN INSTITUTIONAL IRB THAT'S CONVENED IN THE ANTICIPATION OF THOSE THINGS BEING IN PLACE, ACTUALLY DOES DO ADEQUATE RISK BENEFIT ANALYSIS AND SCIENTIFIC REVIEW LIKE HAS BEEN DONE IN THE FEW TRIALS THAT IT'S DONE THIS ALREADY. >> SO THE ISSUE BECOMES WHERE IS THE LINE DRAWN BETWEEN THIS IS A RISK A PATIENT GETTING A TRANSPLANT WOULD DEAL WITH ANYWAY VERSUS WHERE IS THE RISK WHAT HAPPENEDDED TO THAT ORGAN COULD POSSIBLY IMPACT THEM. BECAUSE IT'S ONLY THE PEOPLE FOR WHOM WHAT'S DONE TO THE ORGAN WILL MAKE A DIFFERENCE FOR THEM THAT IT'S URGENT THEY KNOW AHEAD OF TIME WHAT'S GOING TO HAPPEN. >> I THINK THAT'S THE ISSUE. I MEAN, I THINK WE CAN'T ASSUME THE RESEARCH HAS NO IMPACT AT ALL. WE HAVE TO ASSUME IF IT'S RESEARCH THE REASON IS RESEARCH IS THAT THERE'S SOME UNCERTAINTY. PAIB IF WE ARE UNCOMFORTABLE -- MAYBE IF WE ARE UNCOMFORTABLE SAYING YOU CAN'T DO THAT DROC UNTIL A CENTRAL IRB IN PLACE. >> THERE'S THAT UNCERTAINTY IN THE JUST RECEIVING AN ORGAN. SOMEBODY COULD END UP GETTING AN ORGAN WITH WEST NILE IN IT AND -- YEAH. THEY DON'T KNOW. WE KNOW THERE ICE RISK IN -- THERE IS RISK IN IT. WHERE IS THE LINE WHERE THE PERSON HAS NO KNOW ABOUT IT AHEAD OF TIME VERSUS SAYING YOU MIGHT GET AN ORGAN THAT'S HAD RESEARCH DONE. THIS KIND OF GETS BACK TO WHAT WE SLID OVER WHICH IS THE FIRST CONVERSATION OR SERIES OF CONVERSATIONS BUT WHAT IF WE REGARDED AGREEMENT TO RECEIVE OFFERS OF RESEARCH ORGANS AS DIFFERENT ENOUGH FROM AGREEMENT TO RECEIVE EXTENDED OFFERS OF EXTENDED CRITERIA ORGANS SO THAT IT WOULDN'T BE THE CASE AT LEAST I'LL GET TO SOMETHING STEVEN WAS WORRYING ABOUT IN A MINUTE. IT WOULDN'T BE THE CASE THAT YOU WOULD EVER OFFER SOMEBODY A RESEARCH ORGAN WHO SAID NO, I DON'T WANT TO BE OFFERED A RESEARCH ORGAN. WITH THE PROVISO OF COURSE PEOPLE CAN CHANGE THEIR MIND ALONG THE WAY. AND PART OF THE ISSUE THEN IF YOU SAY YES I'M WILLING TO CONSIDER RESEARCH ORGAN, IS THAT PART OF ONE OF THOSE FIRST CONVERSATIONS IS AND HERE IS WHAT IS GOING TO HAPPEN WHEN THE OFFER REALLY COMES, IS YOU ARE REALLY NOT GOING TO HAVE ENOUGH TIME TO THINK ABOUT IT FULLY. SO TAKE THAT INTO ACCOUNT AS PART OF YOUR DECISION MAKING PROCESS. HERE IS THE KIND OF INFORMATION WE MIGHT BE ABLE TO GIVE YOU BUT IT'S NOT GOING TO BE FULL BLOWN, IF THAT IS A PROBLEM FOR YOU THEN DON'T AGREE TO ACCEPT A REESSENTIAL ORGAN. HOW THAT MIGHT CHANGE WOULD BE WITH THE POSSIBILITY THERE'S SO MUCH RESEARCH GOING ON THAT THERE ARE MANY MORE RESEARCH ORGANS OUT THERE THAN STANDARD CRITERIA OR EXTENDED CRITERIA ORGANS. WE MIGHT WANT TO SAY HERE IS A DIFFERENCE BETWEEN THE RESEARCH SETTING THAT WE CAN TALK ABOUT NOW, AND THE CLINICAL SETTING. >> THAT'S BACK TO TWO STAGE CONSENT, IF WE FIND THAT THE SECOND STAGE -- IF WE CAN'T MAKE IT WORK ETHICALLY THEN WE PUT OTHER REQUIREMENTS THAT HAVE TO HAPPEN BEFORE. THAT'S WHERE YOU ARE GOING. >> I DIDN'T HEAR GOING THERE. I THINK IT'S FINE TO PRESSURE TEST MY EXPRESSION PREFERENCE AT THE BEGINNING, I DIDN'T HEAR WHAT WAS BEING PROPOSED AS SUBSTITUTING FOR CONSENT. YOU CAN HAVE YEAR, TWO, THREE FIVE YEARS, IT DOESN'T SUBSTITUTE. I'LL GO ON RECORD. AND MAYBE THIS IS MY ICU CLINICAL EXPERIENCE. I THINK IN THE SPACE OF SPHIEF MINUTES, THREE -- FIVE MINUTES, THREE MINUTES WITH TIME TO REFLECT WHILE YOU ARE CALLING MANY I WIFE, I CAN MAKE A DECISION AS TO WHETHER I WOULD ACCEPT THAT ORGAN BASED ON A PRIOR PREFERENCE I WOULD LIKE TO BE APPROACHED. I THINK IT'S ETHICAL. TO SAY I CAN'T MAKE THAT DECISION BASICALLY ROBS ME OF AN OPPORTUNITY THAT I WOULD OTHERWISE NOT HAVE. TO SAY IT'S UNETHICAL WHERE WE CAN'T DO THAT SO IT'S PERFECTLY ETHICAL EVEN IF I DON'T KNOW OF ANYTHING, NO DROC, NOTHING. I'LL BE RADICAL ABOUT IT, IT'S ETHICAL AND BE A WAIVER FROM A REGULATORY VIEWPOINT OF CONSENT THAT MEETS ALL OF THIS AND THEN SURE I HAVE IN MY HAND SOMETHING WHETHER I GET THAT THROUGH EMAIL, IF I HAVE EMAIL OR FAXED OR IF I HAVE FAXED OR GET AT THE HOSPITAL, I GET THAT AND PROCEED. BUT I THINK IT'S PERFECTLY ETHICAL IN THE SPACE OF THREE TO FIVE MINUTES TO MAKE A DECISION TO ACCEPT AN ORGAN IN THE CONTEXT OF RESEARCH IF I AM A TRANSPLANT CANDIDATE. I WILL GO RIGHT ON SAYING, EVEN IF NOTHING HAS GONE ON BETWEEN THE FIRST AND THE SECOND CONVERSATION AND EVEN IF AT THE FIRST TIME IT WAS JUST E LISSATION OF PREFERENCE, IT'S NOT -- E SOLICITATION. >> I DON'T KNOW WHY WE'RE ARGUING WHEN WE ARE SAYING THE SAME THING. >> YOU CALLED NANCY STAGE OF CONSENT, YOU WANT TO FRONT LOAD IT. I SAID NO. >> MAYBE TO UNDERSTAND THAT WHEN WE SAY A SECRETARIAL WAIVER WE HAVE FREEDOM TO PUT CONDITIONS WHAT MAKES THAT WAIVER CRITERIA SATISFIED. IF PEOPLE FEEL THERE HAS TO BE SOME -- AND I'M NOT SAYING THAT IS WHAT I FEEL, IF PEOPLE FEEL THERE HAS TO BE SOME COMMUNICATION BEFORE, THAT IS AN OPTION WE HAVE. THAT'S ALL. >> IF WE VIOLENTLY AGREE, I'M HAPPY WITH THAT. >> IF I UNDERSTAND A REASONABLE PERSON BASED ON THE PAPER NANCY SENT ME, I'M ONLY TO PAGE 2. WHAT SKIP DESCRIBED IS WHAT WE ARE NOT SUPPOSED TO DO. WHICH IS TO MAKE A DECISION BASED ON WHAT WE, ANY OF US AROUND THE TABLE WOULD DO BUT WHAT THE -- WE SHOULD BE THINKING ABOUT WHAT THE PERSON, THE RANGE OF PEOPLE WHO WOULD BE PRESENTING FOR TRANSPLANT MIGHT DO. AND THEY ARE VARIED BACKGROUNDS, LEVELS OF EDUCATION, EXPOSURE TO RESEARCH, ET CETERA, WOULD DO. NOT ABOUT WHAT AGAIN WE WOULD DO. >> I WAS REFLECTING MY EXPERIENCE WORKING WITH PARENTS AND WHAT THEY WOULD DO AND DECISIONS THEY WOULD MAKE IN SITUATIONS IN CRISIS. I -- OFTEN THERE WOULD BE DECISIONS MADE IN THAT SPACE OF JUST A FEW MINUTES TO DO THINGS LIKE GO ON ECMO. I WASN'T STATING WHAT I WOULD DO, I HAVE NO IDEA WHAT I WOULD DO IF I WAS FACE WITH THIS CIRCUMSTANCE. >> GOING BACK TO THINKING WHAT PATIENTS WOULD DO WITHOUT KNOWING WHAT THEY WOULD DO IN THE ABSENCE HEARING FROM THEM. >> I HAVE A QUESTION FOR THE MEDICAL PRACTITIONERS. IF THE PERSON WERE TO BE ASKED, IF YOU WILL BE WILLING TO ACCEPT RESEARCH ORGAN AND THEY SAID YES I CONSIDER IT, WOULD IT BE POSSIBLE TO SCHEDULE PERIODIC VISITS YOU USE TO INFORM THEM ABOUT WHAT THAT MEANT? AND YOU CAN HAVE A FLAG IN THEIR RECORD SO THAT YOU KNOW THAT THAT IN INFORMATION HAD BEEN AT THIS CUSSED SOFT IT WOULDN'T HAVE TO BE DISCUSSED AT SECOND TIME OF CONSENT? >> I THINK THAT'S VARIABLY POSSIBLE IN THAT THERE ARE PEOPLE THAT ARE -- SEEN REGULARLY AND THERE ARE PEOPLE WHERE THERE ARE LONG GAPS. IF WE THINK IT'S EIGHT YEARS WE WON'T SEE THEM EVERY YEAR BUT BASED ON SOME OF THE CONVERSATION I THINK YOU GUYS THINK AND I THINK THAT THE CONVERSATION ON THAT PHONE EVEN TO ACCEPT THE ORGAN, FORGETTING RESEARCH IS NOT FULL INFORMED CONSENT. THE PERSON IS SAYING YEAH, I -- THE SOUNDS GOOD. I'M COMING IN. YES. AND THEN WHEN THEY COME IN TO THE HOSPITAL EIGHT HOURS LATER YOU PUT THE PIECE OF PAPER AND THEN THE SURGEON COMES AND YOU ARE DOING ALL THAT. BUT THAT IS BECAUSE THEY HAVE HAD THAT EDUCATION, LEADING UP TO IT. SO YES BUT AGAIN, IT'S A BURDEN ON THE SYSTEM I DON'T THINK PATIENTS ARE SUPER RECEPTIVE IN THE LARGE MAJORITY TO COME EXTRA TO THE TRANSPLANT CENTER SIMPLY TO LEARN ABOUT RESEARCH BUT COULD BE BUILT IN TO THE VISITS THEY ARE COMING FOR. >> THEY WOULD BE MOTIVATED SAYING YOU CAN DO THIS. >> BE SURPRISED A PHS INCREASE RISK GEE WE CAN TAKE TWO, THREE FOUR YEARS OFF YOUR WAITING TIME. THEY JUST HAVE A VERY GUT RESPONSE THEY DON'T WANT ORGAN FROM A MAN WHO HAS SEX WITH MEN. SO NOT EVERYTHING PEOPLE ARE DECIDING IS RATIONALE AND YET A WE FEEL BAD IF THEY LIMIT THEMSELVES BE YOU CAN'T FORCE PEOPLE TO EAT APPLE PIE IF EVERYBODY THINKS IT'S SOMETHING GOOD. >> LISTENING TO THIS DISCUSSION. IT WORRIES ME THAT WE IMPOSE A CONSENT REQUIREMENT THAT ENDS UP DENYING PEOPLE THE OPPORTUNITY TO HAVE AN ORGAN THAT MIGHT BENEFIT THEM. WHEN THEY REALLY -- IF WE SAY YOU HAVE TO HAVE THE CERTAIN AMOUNT OF CONSENT MATERIALS BEFORE YOU ARE ALLOWED TO MAKE THE DECISION, THAT WORRIES ME. IF WE HAVE SO MANY CONDITIONS ON THIS PROCESS. >> STANDARD FOR CLINICAL TRIALS. WE HAVE TO DO THAT IN ORDER TO GET A DRUG THAT MIGHT KEEP US ALIVE. BUT YOU ARE NOT IN QUITE SUCH A TIME CONSTRAINT SITUATION ABOUT A CLINICAL TRIAL. >> HERE IT'S THE ORGAN AND SO THE QUESTION IS THE RESEARCH ON TOP OF THE ORGAN. IF -- SO IT'S A LITTLE BIT DIFFERENT BECAUSE YOU ARE MAKING A DECISION BECAUSE OF THE RESEARCH ABOUT IT SEEMS DIFFERENT THAN WHEN MEDICINE IS THE ONLY THING AT STAKE. IF YOU DON'T LIKE THE MEDICINE YOU DON'T GET THE ORGAN. >> I THINK THE OTHER IMPORTANT THING THERE'S OTHER CLINICAL TRIALS IN OTHER CIRCUMSTANCES AND THEY ARE ALSO A LOT OF CLINICAL TRIALS THAT DON'T BENEFIT PEOPLE BUT THEY MAY DPO INTO THEM FEELING THE SAME WAY. I THINK THIS IS DIFFERENT IT SEEMS UNLIKELY THE IRB OR THE SCIENTIFIC REVIEW PANEL WOULD HAVE APPROVED DECEASED DONOR INTERVENTION RESEARCH WHERE THAT ORGAN, YES, THERE ARE UNKNOWNS BUT THE PREPONDERANCE OF THE EVIDENCE SUGGEST THERE'S SOME VARIATION THAT THAT IS IN FACT THE LIFE SAVING INTERVENTION THAT'S BEEN TWEAKED SO IT MAYBE A LITTLE LESS, A LITTLE MORE BUT IT'S NOT -- YOU ARE GETTING THE THERAPY, IT'S MORE LIKE CHOOSING YOU CAN GO ON TRIAL OR GET NOTHING. THE KNOWN THERAPY IT'S EFFECTIVE, THAT'S BEEN TWEAKED SLIGHTLY. WE HAVE TO HAVE A DIFFERENT CONVERSATION IF WE GET INTO THE RESEARCH THAT RADICALLY CHANGES THE LIKELIHOOD OF ENGRAFTMENT OR SURVIVAL. THAT'S NOT WHAT I'M HEARING. THESE ARE THINGS THAT EXTEND THE POOL OF POSSIBLY DONORS, EXTEND LIFE OF THE ORGAN FOR TRANSPLANT. I THINK THERE IS A DIFFERENCE IN THE FACT THAT STILL WHAT THE CONTEXT OF THE DECISION THEY HAVE TO MAKE, 95% IS TO RECEIVE AN ORGAN. THAT'S NOT EXPERIMENTAL. SO I THINK IT'S A LITTLE BIT OF A DIFFERENT CIRCUMSTANCE. THERE'S CLINICAL TRIALS THAT ARE PARALLEL, AS TYPE OF RESEARCH, THIS IS DIFFERENT. >> SO I THINK WE HAVE UNTIL WHAT, 3:30, TO TALK ABOUT THIS? WE ARE NOT GOING TO TAKE A BREAK? WHATEVER PEOPLE WANT. I MEAN, I FEEL LIKE THIS HAS BEEN A REALLY GOODIES CUSHION, IT'S A LOT OF GOOD FOOD FOR THOUGHT AND IDEAS PUT TOGETHER. I WOULD LIKE US TO TALK ABOUT THE PLANNED EMERGENCY RESEARCH WAIVER AND FDA AND HAVE THE GROUP OPINE ABOUT IT. I DON'T WANT TO NOT GET TO THAT TODAY BECAUSE I HAVE TO KEEP WORKING THIS DOCUMENT, THAT'S A CRITICAL COMPONENT. >> CAN I SUGGEST WE TAKE A FIVE MINUTE BIO BREAK. COME BACK AND RECONVENE WITH WHAT WE -- WITH THOSE ISSUES WHAT WE WOULD ACTUALLY PUT INTO A SECRETARIAL WAIVER BECAUSE AGAIN, SECRETARIAL WAIVER IS NOT JUST WAIVER OF CONSENT. WE CAN WAIVER ANYTHING DOWN TO WHATEVER LEVEL WE WANT. >> I ALSO ASK WE KEEP THAT DISCUSSION LIMITED TO 15 MINUTES BECAUSE WE HAVE TO TALK ABOUT PLANNED EMERGENCY RESEARCH WAIVER AND WHETHER THIS COULD FIT IN FOR FDA PURPOSES, I DON'T WANT TO LOOSE THAT. >> LAST WORD. >> ON LIGHTER NOTE I SUGGEST WE TAKE MINIMAL RISK AND REPLACE IT EVERYWHERE WITH THE WORDS TWEAKED SLIGHTLY. I WAS GOING TO ASK IF SOMEBODY FROM HHS COULD SPEND TWO OR THREE MINUTES DISCUSSING PAST SECRETARIAL WAVERS BECAUSE I WONDER IF IT WOULD BE USE TO FEEL THE COMMITTEE TO HEAR WHAT'S BEEN DONE IN THE PAST. EVEN GENERALLY. IT'S NOT SOMETHING THAT A LOT OF PEOPLE HAVE HAD EXPERIENCE WITH. SOME PEOPLE THINK IT WOULD BE HELPFUL TO HEAR SOMETHING ABOUT THAT? DID WE PLAY TAG AND LAURA GOT TAGGED IT? JULIA, I THINK WHEN STEVEN BRINGS UP THE ISSUE OF NOT FEELING COMFORTABLE CALLING IT A WAIVER OF CONSENT, I THINK RAISE THE ISSUE OF WHAT REALLY IS A SECRETARY OF WAIVER, HOW HAS IT BEEN US YOOD IN THE PAST, ONE EXAMPLE WOULD BE HELPFUL. >> SURE. SO THIS IS JUST GOES OFF MEMORY BECAUSE I HAVE NOT -- >> YOU'RE NOT PREPARED? >> I'M NOT. SO TAKE THAT INTO CONSIDERATION. WE HAVE ONLY HAD A HANDFUL AS I RECALL AND THEY ARE ALL IN FACT POSTED ON OUR WEBSITE AS WELL SO YOU GUYS HAVE ACCESS TO THE FACTS BECAUSE I'M NOT GOING TO HIT THEM ALL. WE HAVE GRANTED THEM IN SOME CASES FOR SPECIFIC STUDIES AS I RECALL. BUT THE -- I THINK THE BEST PARALLEL FOR THIS SORT OF WAIVER YOU GUYS ARE CONSIDERING ARE NOT THOSE BUT ONES THAT ARE MORE GENERALLY APPLIED ACROSS TYPES OF STUDIES. SO ONE HAS BEEN DISCUSSED ALREADY WHICH IS COMPARABLE TO THE FDA WAIVER OF INFORMED CONSENT PROVISIONS, 5024 PROVISION WITH A SECRETARY YAL WAIVER THAT PARALLELS TO A LARGE EXTENT THE FDA REQUIREMENTS AND WITH THAT AS YOU HAVE NOTED, THERE ARE MANY CONDITIONS ATTACHED TO THE WAIVER. SO IT'S NOT A WAIVER WITHOUT ANY REQUIREMENTS, IT'S A WAIVER WITH MANY CONDITIONS AND FACTS. AS A REQUIREMENT BEFORE THE WAIVER CAN BE USED. SO KEEP THAT IN MIND AS YOU DELIBERATE ABOUT THIS SORT OF WAIVER, IF YOU WANT GO THAT ROUTE, YOU WANT TO RECOMMEND FOR THIS CATEGORY OF RESEARCH. THEN OTHER WAIVER THAT COMES TO MIND, JULIA IS MOST FAMILIAR WITH, THAT BASICALLY OPERATES ADS ANOTHER CATEGORY OF PERMISSIBLE RESEARCH WITH PRISONERS. SO REGULATIONS IN SUB PART C HAVE REQUIREMENTS THAT THE IRB HAS TO FIND THAT RESEARCH NEEDS CERTAIN CATEGORIES IN ORDER FOR IT TO PROCEED UNDER THE RULE. SO WE DEVELOPED ESSENTIALLY WHAT OPERATES AS ANOTHER CATEGORY OF PERMISSIBLE RESEARCH WITH PRISONERS USING THE WAIVER MECHANISM. SO IT TOO HAS CONDITIONS ASSOCIATED WITH IT IN THAT THE RESEARCH HAS TO MEET WHAT'S DESCRIBED AS PERMISSIBLE UNDER THE WAIVER. I HOPE THAT'S HELPFUL. >> JULIA JUST FLOW ON THAT BY SAYING MEMBERS MIGHT RECALL THAT ON AUGUST 29 I SENT OUT AN EMAIL DESCRIBING PAST USES OF THE SECRETARIAL WAIVER AND LINK TO WHERE YOU CAN FIND INFORMATION ON OUR WEBSITE. >> THANK YOU. SO BECAUSE INTERESTING CONVERSATIONS FREAKILY TAKES PLACE IN BATHROOMS, IT'S BEEN A LONG DAY. LINDA COLEMAN AND I HAD AN INTERESTING CONVERSATION ABOUT -- AND LESLIE, THERE'S TWO TOPICS I WANT TO CONTINUE WITH, ONE IS WHAT A SECRETARIAL WAIVER LOOKS LIKE TO PURSUE THAT. AND SECOND BECAUSE FDA DOESN'T HAVE A SECRETARIAL WAIVER WE HAVE GONE DOWN THE ROUTE OF LOOKING AT THE PLANNED EMERGENCY RESEARCH PROVISIONS TO SEE IF THE RESEARCH COULD FIT INTO THAT CATEGORY FOR THE PURPOSES OF FDA. THE QUESTION THAT WAS RAISED IS WHY NOT JUST USE THAT FOR ALL RESEARCH? WHY HAVE A SECRETARIAL WAIVER FOR HHS AND PLANNED EMERGENCY RESEARCH USE FOR FDA REGULATED AND SO I JUST WANTED TO THROW THAT OUT. STEVEN, YOU LOOK PUZZLED. IN OTHER WORDS IF IT WORKS FOR FDA WHY NOT WORK FOR HHS? >> EXCEPT FOR THE SECRETARIAL WAIVER THAT RECOGNIZES PLANNED EMERGENCY RESEARCH I THINK IF IT WAS UNDER COMMON RULE WHETHER IT WAS UNDER FDA AS WELL OR NOT, IT WOULD STILL HAVE TO SATISFY THE COMMON RULE REQUIREMENTS. I DON'T THINK WE CAN USE A PROVISION THAT'S WRITTEN INTO THE FDA REGS. >> THAT IS ONE OF THE SECRETARIAL WAVERS RIGHT, IS PLANNED EMERGENCY RESEARCH. >> USING THE SECRETARY WAIVER. >> IT'S ALREADY BEEN DONE. I MEAN, IT WOULDN'T HAVE TO BE DONE AGAIN BECAUSE THERE IS A PROVISION FOR DOING PLANNED EMERGENCY RESEARCH FOR HHS FUNDED RESEARCH. >> MAYBE IF WE ARE COMFORTABLE WITH IT MEETING >> I'M SAYING IF WE ARE GOING TO SAY IT COULD MEET PLANNED EMERGENCY RESEARCH REQUIREMENTS FOR DDIR RESEARCH REGULATED BY FDA WHY COULDN'T IT DO THE SAME FOR HHS FUNDED RESEARCH? >> MY CONCERN REMAINS WITH THE IDEA THAT PEOPLE WILL PERCEIVE AS WAIVER OF CONSENT SO I HAVE TO LOOK AT THE LANGUAGE OF THE HHS SECRETARIAL WAIVER TO MAKE SURE. THE FDA WAIVER BASICALLY SAYS IF YOU CAN GET CONSENT YOU SHOULD, IT'S ONLY CIRCUMSTANCES YOU CAN'T THAT YOU DON'T. THAT'S PROBABLY OKAY. I HAVE TO LOOK AT THE OTHER TO SEE WHETHER THAT'S MY MAIN CONCERN. >> I THINK LESLIE MIGHT -- I MAY REFER TO YOU BECAUSE YOU WERE TALKING ABOUT IT BUT THE OTHER PIECE TO IT WOULD BE THAT EVEN IF WE CAN'T RECONCILE THAT PIECE OF IT, THE POINT THAT LESLIE MADE WAS WE COULD TAKE SOME OF THE PRINCIPLES OUTLINED IN THE PLAN EMERGENCY RESEARCH PIECES AND APPLY IT HERE BECAUSE I HAVE HEARD WAS THAT YOU CAN GET A SECRETARIAL WARE AND HAVE CONDITIONS -- WAIVER AND HAVE CONDITIONS ATTACHED TO IT. OR WITHOUT SECRETARIAL WAIVER WHAT THAT LOOKS LIKE, WHAT I HAVE HEARD IS WHAT KINDS OF THINGS OCCUR THROUGHOUT THE PROCESS IN ORDER TO MAKE THIS WORK. I THINK THAT WE COULD BORROW ALL OR SOME OF SOME OF THE THINGS UNDER PLAN EMERGENCY RESEARCH THAT COULD APPLY HERE WITH SOME TWEAKING, I THINK LESLIE YOU HAVE GOOD POINTS, MAYBE TURN IT OVER TO YOU. >> IN READING THE REGULATIONS AND LOOKING NOW IT'S COPIED INTO THE SECRETARIAL WAIVER, I DON'T THINK IT APPLIES. THE PROBLEM IS ONE OF THE PROBLEMS IS OBTAINING INFORMED CONSENT IS NOT FEASIBLE BECAUSE. ONE OF THREE THINGS. THERE'S NO REASONABLE WAY TO IDENTIFY PERSPECTIVELY THE INDIVIDUALS LIKELY TO BECOME ELIGIBLE FOR PARTICIPATION IN THE RESEARCH. HERE WE HAVE A SITUATION WE KNOW WHO ARE LIKELY. WE DON'T KNOW WHICH PEOPLE ARE GOING TO ACTUALLY BE OFFERED A RESEARCH ORGAN BUT UNLIKE A SITUATION WE CAN'T IDENTIFY WHO IS GOING TO HAVE TBI THAT IN FACT WE DO KNOW WHO IS ON THAT LIST. AND THEREFORE I THINK FROM A REGULATORY LANGUAGE WE DON'T FIT. >> SO WE HAVE AN ANALYSIS OF THE EMERGENCY RESEARCH 5024 CRITERIA WHICH WE CAN PUT UP ON THE SCREEN THAT GOES THROUGH THESE. AND MAYBE THAT'S WHERE WE SHOULD START BECAUSE IF WE CAN -- >> THAT'S WHAT I WAS THINKING. >> IF WE CAN MAKE IT FIT THAT. >> THIS WAS STEVEN WHO -- IT'S IN THE BACK, THIS HAS NOT CHANGED. SO WHY DON'T YOU TAKE IT FROM HERE AND I WILL BE HAPPY TO SIT DOWN. >> I'M GOING UP THERE, SANDY. >> I WILL TAKE NOTES. >> I WAS GOING TO SAY AS ONE FAMILIAR WITH PRISONER FININGS, I CAN IMAGINE WE CAN CREATE FINDINGS THAT COULD BE MADE THAT ADDRESS THESE PROBLEMS. THAT COULD BE AN ALTERNATIVE WAY TO GO. NOT WRITE THEM OUT NOW BUT I IMAGINE YOU CAN DESIGN THEM IN A WAY THAT THE IRB WHO APPROVES A PEACE OF RESEARCH THAT IS GOING TO MAKE CHANGES TO THIS ORGAN WOULD HAVE THE MAKE CERTAIN FINDINGS AND THOSE FINDINGS WOULD BECOME AN ASSURANCE THAT THE RESEARCH IS ALLOWABLE. AS A POSSIBILITY BUT SEE IF THIS WILL WORK FIRST. >> THAT IS THE SCHEME FOR THE -- >> STEVEN, ONE CORRECTION TO WHAT WE SAID. THERE WAS A TRIAL THAT WENT UNDER 5024, HAD A WAIVER PEDIATRICS WHICH WAS AN EMERGENCY SETTING STUDY FOR SEE INSURES. IN THAT SETTING YOU NEW KIDS WHO HAD SEIZURES, THAT WAS DONE BECAUSE PARTLY THE INVESTIGATORS WERE ABLE TO DEMONSTRATE THOUGH THEY KNEW WHO HAD A SEIZURE DISORDER THERE WAS NO WAY IN PREDICTING WHO WAS GOING TO COME IN IN STATUS TO BASICALLY PRESENT FOR PURPOSE OF RECEIVING THAT MEDICATION. SO I WOULD ARGUE EVEN THOUGH YOU KNOW WHO IS GONE ON THE TRANSPLANT LIST IF YOU HAVE AN 8 YEAR LONG LIST YOU HAVE NO IDEA WHO WILL SHOW UP AT THAT TIME WHO IS GOING TO BE IN LINE, WHEN THAT ORGAN WILL BECOME AVAILABLE SO THAT DOES APPLY. I WANT TO JUST COMMENT ON THAT. >> SANDY, WHAT YOU DESCRIBED I THINK ARE THE CONDITIONS ARE WHAT WE NEED TO GET TO, THIS APPLIES OR WE NEED A SECRETARIAL WAIVER WHICH WE'LL HAVE EXACTLY WHAT YOU DESCRIBED. >> MARY ELLEN. JOHN. JODY. >> I DON'T THINK IT APPLIES, BECAUSE I THINK WE HAVE IDENTIFIED THE CANDIDATE BASED MATCH. WE SAID THIS ORGAN IS MATCH FOR THIS CANDIDATE. >> WE'LL GET TO THIS BECAUSE WE'RE GOING GO THROUGH THE 5024 CRITERIA. SO WE'LL HAVE THIS DEBATE. THESE ARE THE CRITERIA. FOR BACKGROUND, THERE'S TWO FDA PROVISIONS THAT ALLOW RESEARCH WITHOUT FULLY INFORMED CONSENT, 23 AND 24. READING THEM SEEMS LIKE 23 IS FOR THE INDIVIDUAL USE EMERGENCY RESEARCH. THERE ARE PEOPLE FROM THE FDA HERE WHO CAN ANSWER THIS BUT THIS IS HOW I CAME TO THAT. 24, AT LEAST IT'S BROAD INTENT IS FOR SITUATION WHICH ARE PLANNED WHERE YOU KNOW FROM THE SITUATION THAT YOU ARE DOING THE RESEARCH IS, THAT THERE'S GOING TO BE RESTRICTED OPPORTUNITIES FOR CONSENT. SO I THINK IN THE SPIRIT OF THAT, IT FITS 5024. THAT BEING SAID THERE WERE PARTICULAR REQUIREMENTS PLACED ON 5024, FIRST IS LIFE THREATENING SITUATION AVAILABLE TREATMENTS ARE UNSATISFACTORY SO WALKING THROUGH THAT, OBVIOUSLY IT IS A LIFE THREATENING SITUATION. ALTHOUGH YOU CAN ARGUE THEY ARE ON THE LIST. IF THEY SAY NO, THEY ARE NO WORSE THAN BEFORE. I DON'T KNOW THAT THAT'S -- AVAILABLE TREATMENTS ARE PROVEN AND SATISFACTORY BUT NOT IMMEDIATELY AVAILABLE. OBVIOUSLY COLLECTION IS NECESSARY SO IT'S A BIT OF A MISMATCH ALREADY BUT I THINK IT COULD BE INTERPRETED APPROPRIATELY. TWO IS WHAT WE HEARD ABOUT EARLIER, THE SUBJECTS -- INFORMED CONSENT IS NOT FEEDSABLE BECAUSE SUBJECTS WILL NOT BE ABLE TO GIVE CONSENT AS A RESULT OF THEIR MEDICAL CONDITION. THE INTERVENTION MUST BE AD MINISTERED BEFORE CONSENT FROM L ACTR IS FEASIBLE. AND THERE -- LAR. AND THERE'S NO REASONABLE WAY TO IDENTIFY PROSPECTIVE INDIVIDUALS, ALL THREE MUST BE MET. I THINK EVEN THE FIRST ONE, THE CONSTRAINTS ON CONSENT ARE NOT JUST ABOUT THEIR MEDICAL CONDITION, IT'S ABOUT THE WHOLE ORGAN DELIVERY APPARATUS AS MUCH AS IT IS ABOUT THAT INDIVIDUAL. THAT'S WHAT THAT -- THESE PEOPLE HAVE BEEN STABLE ENOUGH TO SIT ON THE WAITING LIST. WHAT'S HAPPENED IMMEDIATELY IS THE CONSTRAINTS PLACED WHICH ARE NOT ARGUING WITH, THEY ARE CLEARLY NECESSARY, BUT SO ON THE OTHER HAND I PROVIDED ARGUMENTS TO MAKE IT FIT. IT IS A RESULT OF MEDICAL CONDITION. THAT THEY ARE IN THE SITUATION. SAME CONSTRAINTS APPLY TO LAR BECAUSE THEY ARE TIME CONSTRAINTS. IT DOES SAY CONSENT FEASIBLE IN CERTAIN CASE MUST BE OBTAINED WHICH IS REALLY GOOD. THEN TO LESLIE'S POINT, THE POOL OF ELIGIBLE VIJTS IS EXPLICITLY IDENTIFIED. I CALLED IT IN A THROW BACK TO AN EARLIER CONVERSATION. BUT AGAIN THE THIRD REQUIREMENT COULD BE INTERPRETED TO APPLY TO INDIVIDUALS WHOSE DON'T KNOW WHEN IF EVER RECEIVING ORGAN OFFER SO THAT'S TO YOUR POINT ABOUT EPILEPSY. NANCY DIDN'T SEE THAT AS REASONABLE. ALL THESE ADMITTEDLY ARE A STRETCH. I THINK THEY ARE JUSTIFIED POTENTIALLY IF WE AGREE BECAUSE OF THE INTENT OF 5024 WHICH IS DESCRIBE CONDITIONS WHERE YOU HAVE PLANNED RESEARCH AND YOU ARE NOT ABLE TO GET CONSENT. PARTICIPATION HOLDS DIRECT BENEFIT, SUBJECTS FACING LIFE THREATENING SITUATION AND PRE-CLINICAL STUDIES HAVE BEEN CONDUCTED AND RISKS ASSOCIATED WITH INVESTIGATION ARE REASONABLE IN RELATION TO WHAT'S KNOWN ADS THE CBT -- ABOUT THE CONDITION. I THINK THESE ARE SATISFIED. WE CAN QUIBBLE ABOUT LIFE THREATENING IN CONTEXT OF SOMEONE ON TRANSPLANT LIST BUT THEY ARE CONTINGENT ON HAVING ORGAN OFFER FOR THAW LIVES. (OFF MIC) >> WE HAVE -- SO THIS IS WRITTEN INTO THE FDA REGULATIONS. SO WE HAVE -- WE HAVE, FOR THE FDA, WE HAVE A CHOICE OF FITTING THIS INTO EXISTING REGULATIONS THROUGH GUIDANCE OR COMING UP WITH NEW REGULATIONS, WE KNOW HOW LONG THAT TAKES. SO I DON'T SEE ANY OTHER WAY. SKIP. >> I WOULD LIKE TO PROVIDE AN OPPORTUNITY FOR KEVIN TO COMMENT ON FDA ENTERPRETITION OF LIFE THREATENING. WHICH DOESN'T MEAN YOU ARE DYING TOMORROW SO THAT'S HELPFUL TO UNDERSTAND. WE CAN GET BACK TO QUESTION OF IDE IF IING POOL VERSUS WHO IN THAT POOL AT THAT MOMENT OF TIME WILL BE PRESENTED AND WHEN THEY PRESENT, YOU ONLY HAVE 15 MINUTES. GO TO PREVIOUS ONE BUT KEVIN YOU WANT TO COMMENT ON INTERPRETATION OF LIFE THREATENING GENERALLY IN 5024? R, PROTOCOLS? >> THANK YOU. CAN YOU HEAR ME? FIRST I WOULD LIKE EVERYBODY TO KNOW WE HAVE SOME EXCELLENT GUIDANCE ON THIS PARTICULAR REGULATORY REQUIREMENT, IT'S SMALL, 50, 60 PAGES LONG BUT IT COVERS A LOT. I'M SORRY? >> IT'S LIKE IN INFORMED CONSENT. >> EXACTLY. WE'LL HAVE A KEY INFORMATION SECTION UP FRONT SOME DAY. TBU OTHER THING IS THE ISSUE I THINK MANY OF THESE PROVISION ALSO NEED TO BE REINTERPRETED OR REASSESSED IN THE CONTEXT OF RESEARCH. IT'S TRUE LIFE THREATENING IS BROADLY DEFINED BY GUIDANCE, NOT REGULATION. AND COULD BE MODIFIED IF NECESSARY IT IS PLAUSIBLE IN CIRCUMSTANCES IN THIS SITUATION IN MY OPINION PEOPLE ARE FACEING A LIFE THREATENING SITUATION. THE MOST DIFFICULT PART ABOUT APLAYING THIS REGULATION TO THIS TYPE OF RESEARCH IS THE PROVISION THAT LESLIE IDENTIFIED WITH RESPECT TO WHETHER OR NOT YOU COULD PRECONSENT SOME OF THESE PEOPLE. THAT PARTICULAR CASE IT BECOMES A BIT OF NUMBERS GAME. AS TO HOW MANY PEOPLE WOULD YOU HAVE TO CONSENT TO GET NUMBER OF SUBJECTS YOU LIKELY NEED FOR THAT RESEARCH STUDY IF YOU WILL. BECAUSE THE UNIVERSE IS OF -- IN ANY PARTICULAR CONDITION WE KNOW WHO HAS CARDIOVASCULAR DISEASE BUT YOU DON'T WANT TO PRECONSENT EVERYBODY WITH CARDIOVASCULAR DISEASE BECAUSE YOU ARE LOOKING AT A CARDIOVASCULAR END POINT FOR A PARTICULAR STUDY. SAME HERE BECAUSE TALK ABOUT HUNDREDS OF THOUSANDS TO GET TEN PEOPLE WHICH IS SILLY. HERE IN THIS CASE -- IT MIGHT MATTER TO THE NUMBERS. THE PEOPLE WHO ARE WAITING FOR AN ORGAN WHAT THEIR STATUS IS, HOW PLAUSIBLE WOULD IT BE TO GET PRECONSENT THOSE INDIVIDUALS. THOSE TYPE OF THINGS HAVE TO BE ADDRESSED IN PROTOCOL TO ARGUE FOR RESEARCH. >> THESE ARE GIVEN ON A PROTOCOL BY PROTOCOL BASIS. >> ABSOLUTELY, YES. THEY COME IN FOR REVIEW, THEY NEED A SEPARATE IND AND THE REVIEW DIVISIONS GIVEN 30 DAYS TO REVIEW THEM BECAUSE THEY GET A LOT OF OVERSIGHT. >> TRANSPLANT PEOPLE HERE? SPH THAT IS PLAUSIBLE. SOMEONE WRITES A DECEASED DONOR INTERVENTION STUDY INVOLVING RENAL TRANSPLANT SAY, LET'S GO -- WE HAVEN'T BROACHED THE SUBJECT OF OFF TARGET STUFF. THAT'S THERE. NOW YOU HAVE -- YOU HAVE A POPULATION THAT'S ON THE TRANSPLANT LIST AND PERHAPS KIDNEYS WERE NOT FAIR TO TAKE BECAUSE THAT'S THE BIGGEST LIST BUT IS IT PRACTICAL. WHAT IS THE ARGUMENT AGAINST SO THERE'S NOT A LOT OF THESE STUDIES. WHAT IS THE ARGUMENT AGAINST DISSEMINATING CONSENT FORMS FOR THESE STUDIES TO TRANSPLANT CENTERS AND ACTUALLY GIVING THE CONSENT FORMS TO THE INDIVIDUALS WHO MIGHT WANT TO FACE THIS DECISION. AT LEAST RIGHT NOW THIS IS A HANDFUL OF STUDIES, AND HAVING THEIR CARE TEAMS RESPONSIBLE FOR OVER THE NEXT FEW VISITS PRESENTING THIS MATERIAL TO THEM. >> SO I THINK THE -- THERE WOULD BE NO WAY TO SUBSET VERY EASILY WHILE THE AVERAGE WAIT MIGHT BE EIGHT YEARS, SOME PEOPLE WAIT A MONTH BECAUSE THEY ARE SUPER SENSITIZED THEY GET A BUNCH OF POINTS AND CA BOOM, THEY WIN THE LOTTERY BASICALLY. SO THERE WOULD BE NO WAY TO SUBSET WHO -- UNLESS WE DON'T HAVE AN ALGORITHM ONE PERCENT, 10 PERCENT, 30 PERCENT. SO JUST BE DISTRIBUTING, YOU ALSO HAVE TO BECAUSE OF THESE OFF TARGET THINGS SINCE WE ARE TALKING GIVING THINGS TO DONORS AND USUALLY THIS MEANS THAT IT'S GOING TO CIRCULATE YOU BASICALLY NEED TO BE GIVING KIDNEY STUDY INFORMATION TO HEART TRANSPLANT -- IT'S JUST NOT A EFFECTIVE WAY OF COMMUNICATION BECAUSE WHILE THERE MAY NOT BE VERY MANY STUDIES, IT'S JUST A LOT OF STUFF THAT COULD BE REACHING PEOPLE THAT FOR WHICH IT HAS VERY LOW RELEVANCE. >> YOU COULD SEND THINGS OUT. >> I WILL ASK KEVIN HOW THAT WOULD BE VIEWED. SO IT'S NOT REALLY IMPRACTICAL, IT'S A WELL DEFINED -- EVERYBODY IS ON THE LIST. YOU MIGHT MISS SOME PEOPLE WHO JUST GOT ON THE LIST AND WOULDN'T HAVE TIME BUT THEY WOULDN'T HAVE SIGNED A CONSENT AND WOULDN'T BE ELIGIBLE. SO I MEAN, THAT WOULD BE THE MINORITY. MOST PEOPLE WOULD BE ON LONG ENOUGH. THAT MA NOT SIT WELL FROM A CLINICAL POINT OF VIEW BUT FROM RESEARCH POINT OF VIEW. THEN TESTING THIS. SO IN THE PRESENCE OF THAT SITUATION HOW WOULD THE FDA LOOK ON IDENTIFICATION OF THE POOL? >> OF COURSE EACH CASE WOULD HAVE TO BE LOOKED AT INDIVIDUALLY OF COURSE. BUT COLLECTIVELY YOU NEED TO CONSIDER THE FACT THAT THERE MAYBE 15, 20, 30, 50 TYPE OF STUDIES ONGOING ANY TIME TO TRY TO GET PEOPLE TO CONSENT ALL THOSE, MAYBE PART OF THE ANALYSIS WE DO WHETHER OR NOT WE CONSIDER IT IMPRACT CAN BELIEVE TO GET CONSENT. THAT WOULD BE -- A BIT OF POLICY CHANGE THAN IN THE PAST BUT SOMETHING REASONABLE TO CONSIDER. >> OKAY. LEASE MOVE ON BECAUSE WE GO THROUGH ALL THE CRITERIA HERE. SO ARE THERE ANY ISSUES WITH THREE LIFE THREATENING SITUATION? PRE-CLINICAL STUDIES, AND RISKS REASONABLE, WALTER? >> I DIDN'T ENTIRELY UNDERSTAND WHAT DIFFERENTIATES LIFE THREATENING FROM A REGULATORY STANDPOINT WHAT IS LIFE THREATENING OPPOSED TO SOMETHING THAT MIGHT CALL SUB ACUTE. DIABETES UNDER CERTAIN STANDPOINT IS LIFE THREATENING BUT IT MAY BE LIFE THREATENING OVER THE COURSE OF 25 YEARS. >> I UNDERSTAND WHAT YOU SAY AND WOULD BE DIFFICULT MISS IN SOME WAYS TO CATEGORIZE ALL THESE STUDIES AS LIFE THREATENING ESPECIALLY FOR KIDNEY RESEARCH WHERE SOMEBODY MAY OPT TO CHOOSE DIALYSIS AND MAYBE HAVE RELATIVELY LONG HEALTHY LIFE ALBEIT WITH LOTS OF INCONVENIENCESES, CERTAINLY. SO THERE WOULD HAVE TO BE PERHAPS A BIT OF REINTERPRETATION OF POLICY. >> THE GUIDANCE TALKS ABOUT THAT IT DOES HAVEN'T TO BE MORTALITY, IT CAN BE MORBIDITY. IN THE GUIDANCE DOCUMENT CLEARLY SAID THIS WAIVER COULD BE USED FOR STUDY WITH SIGNIFICANT MORBIDITY. >> SIGNIFICANT MORBIDITY CLOSELY ASSOCIATED WITH MORTALITY. THAT'S CERTAINLY CRITICAL. >> AGAIN, JUST A QUESTION. THEN WITH DIABETES QUALIFY AS LIFE THREATENING. ASSOCIATED SIGNIFICANT MORBIDITY SHORT TERM RISK MORTALITY LONG TERM. >> NOT INITIALLY. NOT INITIALLY PERHAPS DOWNSTREAM AS THEY START HAVING MOMENTS END STAGE MANIFESTATIONS OF THE CONDITION PERHAPS. >> WE DID SEE SOMETHING SHARED AT SOME POINT IN THE LAST NINE MONTHS WITH THE GROUP. IT WAS A STUDY THAT SHOWED THAT IF YOU REFUSE AN OFFER FOR WHATEVER REASON YOUR CHANCE OF RECEIVING ANOTHER ONE AND YOUR MORTALITY GOES UP SIGNIFICANTLY. SO I THINK YOU COULD ARGUE THAT THIS PARTICULAR DECISION WAS A LIFE THREATENING DECISION. WE WOULD HAVE TO PARSE THAT OUT. MARK. >> THERE HAS BEEN A RECENT STUDY THAT SHOWS SURVIVAL OF PATIENTS WHO ARE ON DIE DWRALSIS, HEMODIALYSIS IS MUCH WORSE THAN MANY COMMON CANCERS INCLUDING BREAST CANCER FOR EXAMPLE. THE MORTALITY RATE FOR PEOPLE ON DIALYSIS IS IN THE DOUBLE DIGITS PER YEAR PERCENTAGE WISE. SO ACTUALLY WHEN WE REVIEWED STUDIES FOR IMMUNOSUPPRESSION TO PROEVENTUAL PROJECTION WE ALSO STUDIED THAT THAT WAS IMPORTANT THAT WAS REALLY TRYING TO IMPROVE SOMEBODY'S SURVIVAL. >> THANK YOU. >> THAT'S THE TYPE OF DATA THAT WOULD BE VERY HELPFUL IN MAKING THAT DETERMINATION. SO WE EXPECT TO SEE THAT INFORMATION INCLUDED IN THE PROTOCOL. >> I THINK THAT IS THE LITERATURE. OKAY. FOUR, ANY -- THE CLINICAL INVESTIGATION COULD NOT PRACTICALLY BE CARRIED OUT WITHOUT WAIVER. THAT'S WHY WE ARE HERE. SO NO ONE HAS CONCERNS WITH THAT. WE CAN TALK ABOUT WHAT WE'LL DO IF WE DON'T BELIEVE THINGS APPLY. THEVATIONAL PLAN HAS LENGTH OF POTENTIAL -- THIS IS DIFFICULT LIFE OF POTENTIAL THERAPEUTIC WINDOW BASED ON SCIENTIFIC EVIDENCE. AND THE INVESTIGATOR HAS COMMITTED TO ATTEMPTING TO CONTACT LAR FOR EACH SUBJECT WITHIN THAT WINDOW OF TIME AND IF FEASIBLE TO ASKING THE LAR CONTACTED FOR CONSENT WITHIN THAT WINDOW RATHER THAN PROCEEDING WITH THAT CONSENT AND THOSE EFFORTS WILL BE SUMMARIZED. THAT'S VERY SPECIFIC AND HAS TO DO WITH THERAPEUTIC WINDOWS. THAT IS BASICALLY THE HOUR, HALF HOUR THAT WE HAVE. I DON'T KNOW HOW TRANSPLANTERS FEEL ABOUT -- I THINK YOU WOULD BE ABLE TO CONTACT SOMEONE. IT'S KIND OF AN ODD -- IT DOESN'T QUITE MATCH EVEN THOUGH -- THIS WAS THE ONE I HAD HARDEST TIME MAKING FIT BECAUSE IT'S VERY SPECIFIC. SO FDA ANY THOUGHTS HOW THIS MR. PLAY OUT IN THIS SETTING? >> IT WOULD BE A CASE BY CASE SITUATION OF COURSE BUT IT WOULD POTENTIALLY BE REASONABLE CONSIDER THAT HALF HOUR, HOUR WINDOW THAT EXISTS IN ORDER TO OBTAIN CONSENT AS PART OF THERAPEUTIC WINDOW, I DON'T SEE THIS AS BEING AN INSURMOUNTABLE PROBLEM FOR APPLYING THIS WAIVER. >> SKIP. >> THE LANGUAGE IF FEEDSABLE TALKS ABOUT CONSENT, IT DOESN'T TALK ABOUT CONTACT. SO YES YOU CONTACT -- EVEN IN THE CONTEXT SAY OF PEDIATRIC CARDIAC ARREST, COMPARING COULD BE LITERALLY AT BEDSIDE. THERE WITHIN THAT THERAPEUTIC WINDOW, THE QUESTION IS NOT CONTACT WITHIN THAT WINDOW BUT WHETHER YOU CAN GET MEANINGFUL CONSENT WITHIN THAT WINDOW. >> FROM YOUR POINT OF VIEW THIS WOULD BE OKAY. >> THAT'S WHY I ASKED ABOUT TIMING AND WHAT UB ACCOMPLISH IN THAT TIME. I THINK IT FITS. >> EXACTLY. I AGREE WITH SKIP, YOU VERY LEAST INFORM THEM SOMETHING IS GOING ON BUT NOT MAYBE HAVE THE FULL CONVERSATION. >> SO SIX -- >> I WANT TO CLARIFY, SO CONSENT FOR THE ACTUAL TRANSPLANT IS HAPPENING IN ADVANCE OR AT THE TIME, WHEN THEY ARRIVE. IT'S A CHALLENGE TO RATIONALIZE HOW YOU CAN GET CONSENT FOR THE SURGICAL PROCEDURE BUT NOT FOR THE STUDY. >> AT THIS TIME'S A TIME ISSUE. ED FROM GETTING CLINICAL CONSENT WOULD PROBABLY PREEMENT GETTING RECERTAIN CONSENT AND CLOCK IS TICKING, YOU LOSE MORE AND MORE TIME SO ON THAT 30 MINUTE IS IMAGINE SOME IS SPENT GETTING CLINICAL CONSENT AS WELL, SURNLCAL CONSENT. SO TIME IS SHORTER THAN THE 30 MINUTES. >> CONS WE LOW THAT GETS TO BASIC IDEA HERE, I DON'T THINK ANYONE WOULD BE COMFORTABLE NOT ASKING AT TIME OF ORGAN OFFER. BUT THE CONSTRAINTS ON REGULATORY CONSENT ARE VERY SPECIFIC. IT'S HARD FOR THIS TO MEET THE CRITERIA FOR REGULATORY INFORMED CONSENT. BUT THAT DOES GET TO THE PRACT CABILITY ISSUE FOR WAIVER OF CONSENT. >> THIS WILL NEED TO BE FLESHED OUT IN TERMS OF PROCESS, WE ALLUDED TO THAT BEFORE. SO YOU GET A PHONE CALL, YOU LISTEN TO THE SCRIPT THE FIRST THREE FOUR FIVE MINUTES AND SAY SURE. AND YOU GET UP IF NOT IN HOSPITAL PACK YOUR BAG GET A COPY AND THERE'S TIME. IT MAY BE THAT OVER THE COURSE OF THAT COMMUNICATION UNTIL YOU ARE ROLLED INTO THE ROOM THERE'S OPPORTUNITY TO FLESH OUT ALL THE ELEMENTS OF CONSENT THAT WE ARE NOT COVERED OR ABBREVIATED. NOT FROM THE STAND POINT OF PROMPTING THEM TO SAY NO BUT GIVING THEM ALL THAT INFORMATION. SO IS IT THEORETICALLY POSSIBLE BY THE TIME THEY ENTER THE OPERATING ROOM THEY WOULD HAVE GOTTEN THE REST OF THE STUFF? SURE. BUT IT'S HARD TO KNOW IF THAT WOULD OR WOULDN'T HAPPEN. SOME SENSE STARTING WITH THE WAIVER RECOGNIZING -- THE WINDOW COULD BE -- IT COULD BE SHORT, COULD BE AN ORGAN FROM THE HOSPITAL ITSELF, COULD BE WITHIN AN HOUR, COULD BE EIGHT HOURS. ASSUMING YOU HAVE A LOT OF VARYN 'T. >> I THINK A LOT OF PHARMACEUTICAL STUDIES IN PARTICULAR, BECAUSE A LOT OF NIH STUDIES SUPER HIGH RISK THEY ACTUALLY YOU HAVE TO HAVE CONSENT BUT IT DOESN'T EFFECT YOUR ABILITY TO AN ACCEPTED ORGAN, JUST AFFECTS WHETHER YOU'RE GOING TO GET SPECIFIC TREATMENT. A LOT OF PHARMACEUTICAL STUDIES PEOPLE ARE PRESENTED WITH THAT OPPORTUNITY WHEN THEY COME IN. A LOT OF PEOPLE SAY NO. A LOT OF PEOPLE DON'T WANT TO HEAR THE CONVERSATION BECAUSE THEY ARE OVERWHELMED WITH THE IDEA OF TRANSPLANT BUT A LOT SAY YES. OUR CONCERN IS WHEN YOU COME IN YOU ACCEPT THE OR GAN, YOU WANT THE TRANSPLANT AND YOU THINK YOU'RE FINE WITH THIS RESEARCH COMPONENT BUT IF YOU COME IN AND HEAR DETAILS, CHANGING THE MIND OR GOING BACKWARDS HAS A LOT MORE RAMIFICATIONS FOR THE SYSTEM AND THE ORGAN THAN SOMEONE JUST SAYING NO, I DON'T WANT TO PARTICIPATE IN AN IMMUNOSUPPRESSION STUDY AND I WANT MY STANDARD TREATMENT. SO I THINK THE CONCERN IS INFORMATION, YES, HOW FULLY IS THAT INFORMATION ASSIMILATED, IF IT'S BEING PROVIDED DURING THE THIS STRESSFUL PERIOD, EVEN IF THERE IS SOME ADDITIONAL TIME. WHAT MIGHT THE IMPACT BE ON SYSTEM AND ORGAN IF MORE INFORMATION LEADS TO DIFFERENT DECISIONS. THAT IS A BIG ETHICAL QUESTION BECAUSE RVE IT IS THE ORGAN, JUST DIFFERENT CONSIDERATIONS. >> WE ARE TALKING SEPARATELY ABOUT THE CLINICAL CONSENT AND RESEARCH CONSENT AT THE TIME OF THE ORGAN OFFER BUT I THINK IT WOULD HELP IF Y'ALL CAN WALK US THROUGH, THEY ARE NOT SO IN A SITUATION SOMEBODY SAID YES I'LL ACCEPT AN OFFER OF EXTENDED CRITERIA ORGAN, PART OF THAT CLINICAL CONSENT IS GOING TO BE WE HAVE AN ORGAN FOR YOU, IT'S AN EXTENDED CRITERIA ORGAN, AND HERE IS WHAT WE KNOW ABOUT THIS ORGAN. SO HOW IS THAT INCORPORATED INTO THE REST OF THE CLINICAL INFORMATION? WE ARE TALKING ABOUT YOU AGREED TO ACCEPT OFFER OF RESEARCH ORGAN, AND WE ARE OFFERING YOU A RESEARCH ORGAN AND HERE IS THE INFORMATION YOU NEED TO KNOW ABOUT THAT RESEARCH ORGAN IN ORDER TO TAKE THE NEXT STEP. SO SIT'S MORE INFORMATION THAN WOULD BE CONTAINED IN HERE IS THE INFORMATION ABOUT EXTENDED CRITERIA ORGAN BUT IT WILL FUNCTION IN THAT CONVERSATION. IN PROBABLY THE SAME WAY. >> I SEE IT ADS PARALLEL. THE REAL QUESTION IS WHAT IS THE BURDEN OF SCIENTIFIC BACKGROUND RESEARCH INFORMATION, RISK ASSESSMENT, WE NEED TO PROVIDE. BECAUSE THE INCREASE RISK ORGAN AND THE FUNCTIONAL AT RISK ORGAN, WE HAVE SCRIPTS AND PEOPLE HAVE HEARD THIS BEFORE, THESE ARE SOMETIMES CONCEPTS THAT ARE FAMILIAR, IT DEPENDS ON WHAT LEVEL OF INFORMATION WE HAVE TO PROVIDE ABOUT THE RESEARCH INTERVENTION, WHY IT WAS DONE, WHAT IS THE DATA ALL THAT SCIENTIFIC INFORMATION MAY BE DIFFICULT TO ACCURATELY DELIVER AND MAYBE DIFFICULT TO FULLY GRASP TO THE LEVEL OF INFORMED CONSENT. SO I THINK IT'S THAT -- HOW MUCH IS THAT CRITICAL INFORMATION THAT MUST BE COMMUNICATED, IF ALL WE HAD TO SAY IS GEE, THIS WAS A WELL TEST BEEN REVIEWED, IT WAS ASSESSED AS A MODERATE RISK, WE THINK THIS, WE THINK -- SOMETHING FAIRLY STRAIGHT FORWARD. THAT IS ONE THING BUT NOT STANDARD PROCEDURE FOR RESEARCH WHERE CONSENTS AN PROTOCOLS ARE 26 PAGES LONG. THAT'S THE PART WE FIND HARD TO ENCAPSULATE IN THAT TIME. >> EXACTLY, THAT'S EXACTLY WHAT WE ARE TRYING TO GET AT BECAUSE I THINK WE ARE HEADING TOWARD IS SOME DISCUSSION JUST LIKE YOU DESCRIBED THAT THEN GETS FOLLOWED UP WITH THE COMPLETE 25 PAGE CONSENT FORM BUT SOMETHING THAT HERE IS THE KEY FACTS AND INFORMATION YOU NEED TO KNOW SO YOU CAN DECIDE WHETHER OR NOT YOU WANT TO GET ORGAN AND WE'LL FOLLOW THAT UP WITH MORE INFORMATION SO YOU HAVE IT ALL AVAILABLE. >> LET ME JUST REMIND EVERYBODY IN THE DOCUMENT ONE OF THE QUESTIONS WE ARE ASKED IS WHETHER CIRCUMSTANCES IMPACT APPROVAL IRB GIVES TO PROTOCOL, MY RECOLLECTION IS DOCUMENT SAYS YES ABSOLUTELY THESE ARE THINGS WE NEED TO TAKE INTO ACCOUNT. SO THERE IS A LEVEL OF REVIEW AND BOTH SCIENTIFIC AND PARTICIPANT PROTECTION REVIEW HERE THAT WE ARE NOT TALKING ABOUT BUT WE HAVE TO ASSUME CAME FIRST. SO IRB APPROVED RISK BENEFIT RATIO OF THE STUDY IN THIS POPULATION WITH CONSTRAINTS OF CONSENT. THAT'S A GIVEN. WE ARE NOT -- IF THIS CONSENT MODEL -- THERE MAYBE RESEARCH INCRE PLI SCIENTIFICICALLY VALUABLE THAT CANNOT BE DONE IN THIS POPULATION BECAUSE THERE'S NO WAY BECAUSE THERE ARE SUBSTANTIAL RISKS INVOLVED AND NO WAY TO MEANINGFULLY COMMUNICATE THAT AHEAD OF TIME. AND THEN IRB WOULD SAY NO, YOU CAN'T DO THAT. THAT'S THE SITUATION WHERE YOU HAVE TO GIVE THE CONSENT AHEAD OF TIME, THERE ARE OTHER WAYS TO DO IT. BUT IF IT'S VALUABLE ENOUGH. SO I THINK WE HAVE TO BE -- WE HAVE TO START FROM THE POSITION THAT THIS HAS BEEN DEEMED ETHICAL RESEARCH TO DO UNDER THESE CONSENT CONSIDERATIONS. IT'S MORE QUESTION OF HOW WE RESPECT AUTONOMY AND SUCH THAN IT IS -- THAT WE FEEL THIS MAY BE TOO RISKY FOR PEOPLE. IT SHOULDN'T HAVE EVER GONE TO IRB. THE IRB WILL KNOW ALL ABOUT THIS. SO I JUST -- THAT'S JUST A BACKGROUND PIECE BECAUSE IT'S IN THE DOCUMENT, WE HAVEN'T DISCUSSED IT TODAY BUT IT'S IMPORTANT AS WE THINK ABOUT THE KINDS OF RESEARCH THAT MAY GET DOWN UNDER THIS -- DONE UNDER THESE CIRCUMSTANCES. I'M GOING TO ASK -- SO WE WERE SUPPOSED TO END THE WHOLE MEETING AT 3:30. WE STILL HAVE TO DO -- WE HAD RESERVED TIME FROM 3:30 TO 4:30 SO WE'LL USE RESERVE TIME FOR PAY TO PLAY BUT I WANT TO GET THANK YOU THE LAST CRITERIA HERE, I THINK WE SHOULD FINISH THE 5024. ONLY TWO MORE. SIX AND SEVEN. SIX SAYS RECEIVED AND APPROVED U INFORMED CONSENT PROCEDURES CONSISTENT WITH 5025, THESE PROCEDURES IN INFORMED CONSENT DOCUMENT ARE TO BE USED WITH SUBJECT LAR WHEN FEASIBLE. THE IRB REVIEWED AND APPROVED PROCEDURES AND INFORMATION TO BE USED WHEN PROVIDING AB OPPORTUNITY FOR FAMILY MEMBER, ET CETERA. SO I THINK THAT'S TO ME THAT WAS VERY IMPORTANT BECAUSE THAT SAYS IF THERE'S ANY WAY THE DO IT AT ALL, YOU NEED TO DO IT. KEVIN ANY THOUGHTS ON THAT IN THIS SETTING? >> I AGREE, IT'S VERY IMPORTANT PROTECTION BUILT INTO THE ETHICAL REQUIREMENTS. NOT ONLY IS THERE REQUIREMENT TO GET PROSPECTIVE INFORMED CONSENT WHEN FEASIBLE THERE IS A REQUIREMENT TO INFORM PEOPLE OF THE RESEARCH AFTER THE FACT IF IN FACT YOU WEREN'T ABLE TO GET PERSPECTIVE CONSENT SO IT'S CRITICALLY IMPORTANT PART OF THE PROTECTIONS BUILT INTO THE SYSTEM. >> WOULD YOU HAVE ISSUE WITH I APPLYING THAT IN THIS SITUATION? ANY PRACTICAL EXPERIENCE? >> I THINK IT SHOULD BE APPLIED IN FULL AS GREATLY NEEDED. >> 7 IS ADDITIONAL PROTECTIONS, SOME THINGS WE HAVE DISCUSSED SO THIS DOESN'T FIT EXACTLY BUT MAYBE IT DOES. WHAT WE CALL IRB WORLD COMMUNITY CONSULTATION. DOES THAT MEAN CONSULTATION WITH TRANSPLANT COMMUNITY OR MECHANISM -- HOW IS THAT GENERALIZED TO THIS SITUATION, KEVIN? >> I PERSONALLY HAVE NOT SEEN AN -- THIS TYPE OF POPULATION BUT I WOULD EXPECT THIS THEY WOULD REACH OUT TO THE PEOPLE ON THE TRANSPLANT LIST TO INFORM THEM OR TO EDUCATE THEM ABOUT THE RESEARCH BEING PROPOSED. >> WE TALKED AT VARIOUS TIMES ABOUT OUR WEBSITE OR SOMETHING. SO WOULD IT BE FEEDSABLE FROM THE TRANSPLANTERS PERSPECTIVE TO GET WORD OUT TO THE COMMUNITY, NOT INFORMED CONSENT, BUT BASICALLY TO MAKE INDIVIDUALS AWARE OF THE RESEARCH GOING ON? >> I SHOULD CLARIFY, THERE'S TWO ASPECTS TO THIS, PUBLIC DISCLOSURE WHICH IS ONE WAY COMMUNICATION OCCURS WITH WEBSITE OR FLYERS THAT YOU PUT AROUND BUT THEN THERE'S COMMUNITY CONSULTATION WHICH IS SORT OF A TWO WAY CONVERSATION, DIALOGUE WITH THE PEOPLE LIKELY TO BE ENGAGED IN THE RESEARCH. IN THE COMMUNITY FOR WHICH THEY WILL BE DRAWN. THAT'S THE GOAL OF THAT IS TO TEST WATERS IF YOU WILL TO TRY TO GET UNDERSTANDING OR APPRECIATION OF WHAT OBJECTIONS THESE PEOPLE MAY HAVE ABOUT THIS TYPE OF RESEARCH. >> COULD YOU SATISFY THAT HAVE DO YOU THINK IF YOU HAVE THIS SPECIALIZED IRB? IT HAS A FIXED NOT JUST ONE PERSON, BUT FIX REPRESENTATION FROM THE COMMUNITY ON THE IRB RESEARCH? >> NOT AT ALL. I HAVE NO PROBLEMS WITH THE SPECIALIZED IRB LOOK AT THIS TYPE OF RESEARCH BUT IT'S STILL THAT WOULDN'T CONSTITUTE COMMUNITY CONSULTATION AS INTENDED BY THE REGULATIONS. >> ANY THOUGHTS HOW PRACTICAL THIS IS FROM -- IN A TRANSPLANT COMMUNITY? >> I HAVE NO IDEA -- >> HERE IT IS EASIER THAN IN OTHER SETTINGS. YOU HAVE A LIST OF PEOPLE AND ADVOCACY GROUPS SO YOU HAVE A COMMUNITY THAT CAN BE ENGAGED IN A PROCESS AROUND THIS. THERE'S NO SPECIFICATION WHAT IS THE NATURE OF THE CONSULTATION OUGHT TO BE ACCEPT KEVIN MENTIONED TWO WAY, YOU ARE HAVING A CONVERSATION WHETHER YOU USE FOCUS GROUPS OR SURVEYS OR TOWN MEETINGS, ET CETERA THERE IS A WHOLE LOT OF DIFFERENT PROCEDURES THAT CAN BE USED. THE OTHER INTERESTING PART IS IN WHICH THE CLINICAL INVESTIGATION WILL BE CONDUCTED AND FROM WHICH THE SUBJECS WILL BE DRAWN, I HAVE INTERPRETED THAT TO MEN MEAN NOT ONLY TRANSPLANT COMMUNITY OF SUBJECTS AND LOTS OF CONVERSATION REACHING OUT TO THEM BUT INVESTIGATORS SURGEONS ET CETERA TO HAVE A CONVERSATION WITH THEM ABOUT THIS AS WELCH SO I SEE IT ADS BOTH. >> CAN I JUST CLARIFY. I'M HAVING REALLY HAVE TO WORK WITH THIS BEFORE. THE END RESULT OF THIS IS IF YOU COULD MAKE ALL OF THESE FINDINGS FIT INTO THIS SITUATION,S THAT YOU WOULD BE ABLE TO IMPLANT AN ORGAN THAT WAS A RESEARCH ORGAN WITHOUT TELLING THE PATIENT IN ADVANCE THAT YOU WERE DOING THAT. >> THE INTENT IS, IF IT'S FEASIBLE TO GET CONCEPT -- >> I KNOW. >> SITUATIONINGS WHERE IT'S NOT FEEDSABLE. SITUATIONS WALTER BROUGHT UP WHERE MENTAL STATUS IS CHANGED FROM THE USUAL SITUATION. >> Q. YOU ALWAYS HAVE A HALF OUR OR HOUR. YOU ARE ALWAYS IN TIME CONSTRAINED SITUATION. SO AND MAKING THAT A KEY FEATURE OF THIS TO JUSTIFY IT. SO I JUST WONDER IN THE END IS THERE ANY PEOPLE WHO WILL BE SURPRISED AFTER THE FACT TO FIND OUT THAT THEY ARE ORGAN IS A RESEARCH ORGAN? >> I THINK -- >> I WOULD SA SAY NO. STEVEN, YOU WENT BACK TO WHAT I WAS GOING TO SUGGEST. AN OPPORTUNITY FOR FAMILY MEMBER IN THIS CASE WOULD BE POTENTIALLY A COMPETENT TRANSPLANT RECIPIENT PERHAPS TO OBJECT. DURING THIS SCRIPT PRESENTATION, IN OTHER WORDS -- (OFF MIC) >> I'M ASSUMING WHAT WE TALKED ABOUT IN TERMS OF PROCESS THAT HAPPENS THAT THERE WOULD BE THAT SCRIPT THAT GOES ON AND THAT WOULD BE THE IRB WOULD REVIEW THAT AND WOULD CONSIDER THAT ADEQUATE FOR THIS QUICK EXCHANGE. THAT WOULD BE -- NO ONE SHOULD GET AN AN ORGAN THEY DON'T KNOW ABOUT. >> IT GETS BACK TO THE IDEA OF JUST A WAIVER OF CONSENT. INTERPRETATION OF THIS EITHER IN GUIDANCE OR IN THE CONTEXT OF INDIVIDUAL STUDIES WOULD HAVE TO SPELL THAT OUT. THIS IS NOT WAIVER OF INFORMED CONSENT THOUGH WE KNOW FULL INFORMED CONSENT PER REGULATIONS IS NOT FEASIBLE YOU STILL HAVE TO DO WHAT YOU CAN IN THE INDIVIDUAL CASE WHETHER THAT'S KEY INFORMATION OR SOMETHING THAT WANTS TO BE -- NEEDS TO BE SPECIFIED. REQUIREMENTS ARE ALSO THE IRB APPROVE A CONSENT PROCESS AS SUCH. >> I WOULD ACTUALLY SUGGEST THAT ONE OF THE FUNCTIONS OF THIS CENTRAL SINGLE IRB WOULD BE TO WRITE THE SCRIPT. BECAUSE THEN THEY COULD -- THE BEST PLACE AND ESTIMATE ON THE RISK BECAUSE THEY HAVE SEEN THE SCOPE OF THE VARIOUS STUDIES BEING DONE AND THAT COULD BE MUCH BETTER STANDARDIZED, THAT COULD BE READILY ACCESSIBLE IN THE ID MIDDLE OF THE NIGHT THAN PHYSICIANS -- THE DESCRIPTION SHOULD COME AS A PRODUCT OF THE REVIEW OF THE STUDY AND THE APPROVAL OF THE STUDY AND THEREFORE THE IRB SHOULD IDENTIFY WHAT ARE THE KEY ELEMENT -- ALL THOSE THINGS, THAT COULD BE A SPECIAL FUNCTION OF THIS PARTICULAR TYPE OF IRB. >> THE EXERCISE WE ARE DOING HERE IS TO SEE IF THIS KIND OF RESEARCH CAN BE FIT UNDER 5024. IT'S NOT TO SAY THAT IT WOULD FIT UNDER 5024 WITHOUT ADDITIONAL GUIDANCE AND OTHER DOCUMENTATION. SO I THINK WE HAVE TO ASSUME THERE WOULD HAVE TO BE GUIDANCE WHETHER GENERAL GUIDANCE OR GUIDANCE IN THE CONTEXT OF INDIVIDUAL STUDIES ABOUT HOW TO APPLY THIS SO INDIVIDUALS ARE PARTICIPANTS ARE PROTECTED. OUR CHOICES ARE LIMITED UNDER THE FDA RULES BECAUSE THERE'S NO OTHER WAY TO DO THIS WITHOUT GETTING FULL RESEARCH CONSENT EXCEPT 5023 WHICH WE ARE NOT DISCUSSING. IF IT DOESN'T FIT WE HAVE TO THINK OF SOMETHING ELSE BUT FITTING IT IN WOULDN'T BE JUST -- IT WORKS, LET'S GO AHEAD, IT WOULD BE MORE SCRUTINY THAN THAT. KEVIN. >> AGREE, I THINK USING THE INFORMED CONSENT REQUIREMENTS AND EMERGENCY RESEARCH, IS POTENTIALLY AN OPTION BUT SOME NEW GUIDANCE MAY NEED TO BE WRAPPED AROUND IT SO WOULD BE HELPFUL IF SACHRP COULD SUGGEST SOME WAYS OF INTERPRETING THINGS OR LOOK AT THESE THINGS TO ALLOW US TO MOVE FORWARD WITH THIS TYPE OF RESEARCH. >> LET ME JUST GO THROUGH THE LAST REQUIREMENTS IN 7. PUBLIC DISCLOSURE TO COMPRISE COMMUNITY AND RESEARCHERS, I DON'T THINK THAT COULD SHOULD BE A PROBLEM. ESTABLISHMENT OF INDEPENDENT DATA MONITORING COMMITTEE PROBABLY GOES ON IN THIS KIND OF STUDY BUT I DON'T KNOW, IT COULD. >> THIS LAST ONE IS ONE WE DISCUSSED EARLIER IF CONSENT IS NOT FEASIBLE AND THEN -- NOT AVAILABLE ATTEMPTING TO COMMIT CONTACT A MEMBER OF THE FAMILY, I THINK THAT'S REALLY TWO IFs PROBABLY NOT GOING TO COME UNTO PLAY HERE. AND THEN SO THAT'S IT. THE SENSE I GET IS WITH -- THERE'S NOTHING -- THE STRONGEST OBJECTION TO THIS HAS BEEN THE ONE ABOUT IDENTIFYING COMMUNITY AND WHAT FOLLOWS FROM THAT. I THINK WOULD IT BE HELPFUL IF SACHRP OPINED ON WHAT COMMUNITY CONSULTATION -- FROM MY PERSPECTIVE WE CAN SHOE HORN THIS RESEARCH INTO THIS EXCEPTION. WITH GUIDANCE, EXCEPT LESLIE. >> IT'S NOT JUST THE POINT I MADE BEFORE BUT OTHER PARTS OF THE CRY TIER YOUION, YOU ARE PROVEN WAS UNPROVEN TREATMENT. THERE'S SEVERAL WAYS YOU ARE SHOE HORNING WHICH I THINK ARE IS A BIG STRETCH FOR SOMETHING THAT HAS BEEN CONTROVERSIAL SINCE IT WAS ADOPTED NECESSARY IMPORTANT BUT CHALLENGING. THAT I THINK CREATES PROBLEMS. I AM UNCOMFORTABLE WITH. >> I CAN COMMENT AS WELL, I AGREE WITH WHAT WAS JUST SAID TRANSPLANT BY FDA, IT IS SHOE HORNING IN FROM MY PERSPECTIVE AS A REGULATOR, AND CLINICIAN AND REALLY A PROBLEMATIC FASHION AMONG SEVERAL FUNCTIONS IT IS AT THE END OF THE DAY NOT CONSISTENT WITH WHAT THE 5024 APPROACH IS AIMING TO DO. I THINK THAT THE TRANSPLANT COMMUNITY OF PATIENTS BY THE TIME THEY ARE PRESENTED WITH -- REALLY ARE A VULNERABLE POPULATION, IN DOING ANYTHING TO AN OR GAN UNDER RESEARCH PREMISE IS CLINICALLY SPEAKING, SIGNIFICANT RISK. ONE DOESN'T UNDERSTAND THE LONGER TERM OUTCOMES. THAT REALLY IS WHAT TRANSPLANT PATIENT ULTIMATELY WILL CARE ABOUT. THEY DON'T WANT A (INAUDIBLE) ORGAN TODAY T. ONE YEAR TWO YEARS FROM NOW NOT LINKED AS EXPECTED. 5024 WOULD HAVE A HARDER TIME RECONCILING ALL THE -- >> THAT TAKES US BACK TO -- THANK YOU. I THINK IT DOESN'T FIT. THE REASON WHY I THINK IT WAS WORTH TRYING. OR IS WORTH TRYING I THINK THE INTENT IS TO BE ABLE TO DO RESEARCH AT A PLACE AT A TIME WHERE TRADITIONAL CONSENT IS NOT FEASIBLE. THAT WAY THE SITUATIONS ARE ANALOGOUS, THAT SETS IT APART. IT'S PLANNED RESEARCH, YOU KNOW ALL THIS. IT'S LITTLE DIFFERENT THAN 5023. THE FDA REGULATIONS DON'T HAVE A SECRETARIAL WAIVER SO THE ONLY WAY NOT TO MEET THE FULL CONSENT REQUIREMENTS ARE 5023 AND 5024. IS THERE SOME OTHER -- THAT WAS THE PURPOSE OF THE EXERCISE, IF IT DOESN'T FIT THEN WE HAVE TO THINK OF SOMETHING ELSE. I DON'T KNOW OTHER WAY TO DO IT THAN RULE MAKING. THAT MAYBE FINE, THAT MAYBE WHERE WE ARE. >> PERSONALLY I DON'T THINK IT'S THAT FAR OF A STRETCH TO MAKE IT FIT THOUGH I REALIZE IT'S CONTROVERSIAL BUT CURIOUS TO HEAR WHAT THE OPTIONS ARE BECAUSE I RULE MAKING I KNOW THAT'S -- COME ON, LET'S BE REALISTICMENT WHAT ARE THE OPTIONS OTHER THAN 23, 24. I HAPPEN TO THINK THIS FITS, I DON'T THINK IT'S A BIG STRETCH, I DON'T THINK IT'S PROBLEMATIC. SO I'M OPEN TO HEAR OTHER SOLUTIONS TO WHAT IS A COMPLEX QUESTION, CURIOUS WHAT THOSE MIGHT LOOK LIKE. >> WHAT I THIS I WORKS AT THIS POINT WOULD BE FOR THE WAY WE STARTED ONE OF THE WAYS WE STARTED TALKING ABOUT LOOKING AT 5024 WAS CAN WE USE THIS AS A TEMPLATE THAT'S MODIFIABLE FOR THE PURPOSES OF THE SECRETARIAL WAIVER AND IF WE WORK THROUGH THAT AND DECIDE WHAT WE NEED THEN WE'LL HAVE A REALLY MUCH BETTER ROADMAP TO ADDRESS THIS QUESTION OF WHETHER OR NOT THERE'S TOO MUCH SHOE HORNING WITH 5024 BUT OUR FIRST QUESTION REALLY, IT WOULD BE GREAT IF WE COULD ADDRESS THE 5024 PROBLEM BUT IF WE START WITH WHAT DO WE NEED FOR THE SECRETARIAL WAIVER AND WHICH OF -- IF -- AND START WITH THIS TEMPLATE INSTEAD OF STARTING FROM SCRATCH IT WILL GET US FARTHER ALONG. >> THE REASON WE DID IT THIS WAY IS PARTLY BECAUSE IF WE WERE COMFORTABLE UNDER 5024, WE CAN USE EXISTING SECRETARIAL WAIVER FOR THE COMMON. BUT I'M SENSING THERE'S NOT CONSENSUS ON THAT THE COMMON RULE PROBLEM IS EASIER. WE CAN COME UP TO AN ANSWER THAT WILL SATISFY THAT WILL LET US DRAF RESTRICTIVE OR NOT SO RESTRICTIVE SECRETARIAL WAIVER FOR THIS CIRCUMSTANCE BY DOING EXACTLY THE THINGS WE WANT TO DO AND THINK ARE ETHICALLY RIGHT, THE PROBLEM WILL BE I ANTICIPATE THIS RESEARCH WILL BE WITH DEVICES OR DRUGS AND WILL BE BACK WITH NO MECHANISM FOR FDA TO REVIEW IT. BUT IF WE JUST ACCEPT THAT AND SAY OKAY, LET'S TABLE THIS FOR NOW, LET'S SEE WHAT WE CAN COME UP WITH THE SECRETARIAL WAIVER KEEPING IN MIND WHERE IT DOES AND DOESN'T FIT WITH 5024 MAYBE THE THINGS WE PUT IN PLACE FOR THE SECRETARIAL WAIVER WILL HELP US BE COMFORTABLE WITH USING 5024 AND PUT CONSTRAINTS ON 5024 THAT WILL BE OKAY. I WOULD PROPOSE THAT AS THE WAY FORWARD. IT'S WHAT NANCY SUGGESTED LOOKING AT THE SECRETARIAL WAIVER CRITERIA. THERE ARE NO -- THE SECRETARIAL WAIVER IS WIDE OPEN. WE CAN DO WHATEVER WE WANT. SO START WITH WHAT DOESN'T FIT HERE, ADOPT WHAT FITS. MAKE THE SECRETARIAL WAIVER AS CLOSE AS POSSIBLE TO 5024 AND SEE WHEN YOU PUT TWO SIDE BY SIDE WHETHER YOU CAN BE COMFORTABLE WITH THE FACT THEY ARE ALIKE IN FACT OR SPIRIT. SKIP. >> I THINK THAT'S A FINE PROCESS BUT WHAT I WOULD ALSO ASK, I DON'T KNOW HOW DIFFICULT THIS WOULD BE, THERE IS A LOT OF EXPERIENCE ALREADY WITH APPLICATION 5024, I KNOW SOME OF THEM. THAT ADDRESS PARTICULARLY WHAT I HEAR IS CONTROVERSIAL ISSUE, ISSUE OF FEASIBILITY. PRE-SIDE FICATION POPULATION HOW WELL YOU CAN IDENTIFY WHETHER SO ISSUE IN THE PEDIATRIC STUDY WHERE INVESTIGATORS WNT THROUGH WHOLE STUDY LOOKING AT THAT QUESTION FEASIBILITY AND THE FDA AND OHRP WILLING TO APPLY SECRETARIAL WAFER, THAT WAS HHS CONDUCTED STUDY. IT WOULD BE INTERESTING TO GET THE DATA. I DON'T KNOW HOW EASY SUCCESSFUL TO SEE BUT WHAT WAS THE FEASIBILITY STUDY THEY DID, HOW MANY DID THEY IDENTIFY, ARGUMENT MADE AROUND FEEDSIBILITY, ET CETERA, THERE MAYBE OTHER EXAMPLES WE CAN LOOK AT TO PROVIDE SOME CONTEXT AROUND THAT DECISION OPPOSED TO WE KNOW WHO THEY ARE THEREFORE WE CAN GET THEM. WE KNEW WHO EVERYBODY WAS THAT HAD SEIZURES SO YEAH WE COULD IDENTIFY THEM BUT WHEN YOU ARE TRIED TO DRILL DOWN IT WAS TRULY NOT FEASIBLE TO KNOW WHO WAS THEN GOING TO BE STATUS EPILEAPT CUSS FOR EMS SYSTEM. SO THAT WOULD BE ONE REQUEST CAN WE GET INFORMATION AROUND HOW THAT'S BEEN APPLIED. >> IT IS AN INTERESTING PROPOSAL BUT AFRAID TO SAY THERE'S NOT TO MY KNOWLEDGE THAT MUCH EXPERIENCE WITH THIS ISSUE CONTROVERSIAL IN ANY PARTICULAR PROTOCOL THAT I HAVE REVIEWED. I HAVE BEEN DOING THIS FOR SIX YEARS. IT'S COME UP MAYBE TWO, THREE TIMES WHERE THERE WAS A DEBATE TO WHETHER OR NOT IT WAS POSSIBLE TO PRECONSENT PEOPLE. IT NORMALLY CAME DOWN TO A NUMBERS GAME HOW MANY PEOPLE YOU HAVE TO CONSENT IN ORDER TO IDENTIFY TEN PEOPLE THAT YOU NEED FOR THE STUDY, WHATEVER THE NUMBER PLANNED FOR THIS STUDY. SO IT'S THIS IS A UNIQUE SITUATION I THINK. >> SANDY. >> SO I'M NOT FAMILIAR WITH THE FDA RULE, BUT IN THE END OF THE DAY, WHAT THE FDA DOING IS SAYING IF YOU MEET REQUIREMENTS FOR 5024A YOU DON'T NEED TO PERFORM CONSENT? OR YOU DON'T NEED TO PERFORM FULL CONSENT? WHAT IS THE DETERMINATION YOU MAKE WHEN YOU SAY SOMETHING FITS THE 5024A? >> YOU NEED TO DO IT TO EXTENT -- YOU NEED TO WRITE EXTENT, DO IT TO EXTENT FEEDSABLE IN THE SITUATION. AND I THINK WE HAVE TO -- THIS IS A UNIQUE SITUATION AND WE HAVE TO FLESH THAT OUT. I'LL ASK KEVIN JUST TO CLOSE THIS BECAUSE THEN I WANT TO MOVE ON TO PAY TO PLAY FOR THE LAST HALF HOUR. THIS IS -- SO IF WE DECIDE THIS IS ETHICAL, AND QUESTION OF FITTING TO REGULATION THE QUESTION IS WHETHER THE FDA IS COMFORTABLE MAKING THE 5024 EXEMPTION IN SOME OF -- IN THE PROTOCOL BY PROTOCOL BASIS BUT WHETHER THAT'S A FEASIBLE APPROACH. >> IT HAS A POSSIBILITY I WOULD SAY. I DO WANT TO CLARIFY, WE DO CONSIDER THIS WAIVER OF CONSENT. HOWEVER THERE IS AN OBLIGATION TO GET PROSPECTIVE CONSENT WHEN FEASIBLE AND WE EXPECT IF NOT POSSIBLE TO IN THE VERY LEAST INFORM PEOPLE OF THE CRITICAL ISSUES AROUND THE RESEARCH, THAT WOULD BE AN EXPECTATION. AND IN THIS TYPE OF RESEARCH I THINK THIS WOULD BE TIME IN MOST CIRCUMSTANCES BE ABLE TO AT LEAST TELL PEOPLE ABOUT THE KEY ELEMENTS OR THE KEY ISSUES CONNECTED TO THE RESEARCH. >> JOANNE, LAST WORD. >> I WANT TO SAY THIS IS WHERE LESLIE IS HAVING A CONCERN, I'M ALSO HAVING ISSUE WITH WHERE IT SAYS SUBJECTS ARE NOT ABLE TO GIVE INFORMED CONSENT AS A RESULT OF MEDICAL CONDITION. WHAT WE TALKED ABOUT EARLIER WAS WAIVING 5020 WHERE THEY DON'T& HAVE SUFFICIENT TIME TO MAKE THIS DECISION WITHOUT UNDUE INFLUENCE AND COURSE OF ATMOSPHERE. THIS WAIVER IS TOTAL WAIVER OF INFORMED CONSENT UNLESS YOU CAN GET IT. YOU CAN TRY BUT IF NOT WAIVE COMPLETELY WHERE IT'S -- THAT CRITERIA THERE IS THE ONE I STRUGGLE WITH MOST BECAUSE IT DOESN'T GO WITH WHERE WE WHERE EARLIER THE SAY YOU CAN TELL THEM ALL THESE THINGS BUT THE THINGS THAT IS HUNG UP ON SO WE ARE SAYING IT DOESN'T SATISFY THE REGULATORY INFORMED CONCEPT. HERE WE WILL BE WAIVING THE ENTIRE THING. >> IN YOU ARE RIGHT, THIS WOULD HAVE TO BE ACCOMPANIED BY GUIDANCE, THAT'S NOT WHAT WHAT WE -- HOW WE ARE INTERPRETING IT IN THIS CASE AND WHEN YOU REVIEW PROTOCOL TO GIVE IND OR IDE IT DOES CALL FOR PROPERTIED COL SPECIFIC CONSENT PROCEDURES TO BE APPROVE BID THE IRB. IT HAS TO BE CLEAR WHAT THOSE WERE. IT IS A E CROO YEAHTIVE INTERPRETATION NO DOUBT ABOUT I. WITH THAT WITH TOTAL LOOK OF CONSENSUS WE SHOULD STOP, I WAS WRONG, I HAVE TO ADMIT FOR EVERYTHING ON THIS AGENT DARKS NEXT TWO YEARS. BUT I WILL INVITE DAVID TO COME UP AND SWITCH TO THAT. >> I'M BACK. ALL RIGHT. OUR LAST DOCUMENT IS PAY TO PLAY DOCUMENT, I WILL BRING UP THE CLEAN VERSION. THIS HAS BEEN SEEN BEFORE AND BACK AND FORTH WITH SUB COMMITTEE AS WELL AS PARENT COMMITTEE, I WON'T MAKE ANY GUESS AS TO THE HOW IT WILL SURVIVE THE NEXT HALF HOUR T. THIS IS -- I WOULDN'T CALL -- I DON'T KNOW IF IT'S A BOOK END DOCUMENT BUT THIS IS SOMETHING THAT GREW OUT OF OUR WORK ON PAIN RESEARCH PARTICIPANTS IN THE CONTEXT OF STUDY PARTICIPATION, THIS FLIPS THINGS AROUND A BIT AND ASK WHAT ABOUT SCENARIOS WHERE INDIVIDUALS ARE ASKED TO PAY IN ORDER TO PARTICIPATE IN A CLINICAL TRIAL. WITHIN THIS DOCUMENT WE DO DIFFERENTIATE BETWEEN FULL PAYMENT TO PARTICIPATE AND PARTIAL PAYMENT TO PARTICIPATE. WE WERE ASKED TO TAKE ON THIS TOPIC BECAUSE WE ARE SEEING ANECDOTALLY IRBs ARE SEEING UPTAKE IN TYPES OF TRIALS DESCRIBED HERE. THIS IS NOT MY DOCUMENT, THIS IS DAVID FORESTER'S DOCUMENT AND I WILL DO MY BEST TO WALK THROUGH IT. I'M FAMILIAR WITH IT AND AS I SAID IT'S BEEN TO THE NOT ONLY THIS COMMITTEE BUT THE SUB COMMITTEE A NUMBER OF TIMES. A LOT OF BACKGROUND AND THE GOALS ARE FAIRLY STRAIGHT FORWARD IF THERE ARE ANY EDITORIAL COMMENTS, I'M HAPPY TO TAKE THEM BEFORE JUMPING THE MEAT OF THIS DOCUMENT. THE GOAL IS TO PROVIDE STAKEHOLDERS WITH POINTS TO CONSIDER IN ASSESSING STUDIES OF THIS NATURE AND AGAIN PRODLY SPEAKING WE SAY BROADLY THERE'S TWO VARIATIONS ON PAY THE PLAY BOTH WHICH DIVERGE FROM THE IDEA A SPONSOR WHETHER FEDERAL OR OTHERWISE IS COMPLETELY PAYING FOR THE COST OF BEING IN THE STUDY SO WE HAVE FULL PAY TO PARTICIPATE TRIALS AND PARTIAL PLAY TO PARTICIPATE AND THE FULL PAY TO PARTICIPATE ARE SUBJECT ESSENTIALLY FUNDING THE ENTIRE TRIAL FROM TEST ARTICLE TO STUDY INTERVENTIONS, DATA COLLECTION ADMINISTRATIVE COST ET CETERA AND THE PARTIAL PAY TO PARTICIPATE TRIALS ARE THOSE SUBJECTS MAYBE CHARGED FOR ONLY CERTAIN COSTS SUCH AS TEST ARTICLE OR FOR A SPECIFIC DIAGNOSTIC TEST OR SOME COMBINATION THEREOF. THE THING THAT IS THE SAME IS SUBJECTS ARE BEING ASKED TO HELP FUND THE IMPLEMENTATION OF THE RESEARCH STUDY. AND WE ALSO CALL OUT A FEW THINGS THAT ARE OUTSIDE SCOPE OF THIS, SUCH AS ROUTINE BILLING FOR MEDICAL COSTS, NORMALLY CLINICAL CARE ALSO TO PATIENTS IN CLINICAL TRIALS SUCH EXAMPLE IS THE COST OF ANTI-MEDIC ONCOLOGY CARE AN ONCOLOGY CLINICAL TRIALS. SO MOVING ON TO -- I'M GOING FAST WAS BECAUSE I'M WARY OF THE TIME AND I WANT TO GET THROUGH IT AND THIS IS BACKGROUND SO PUT YOUR CART UP OR RAISE YOUR HAND AND I WILL PAUSE. WE TALK ABOUT MOTIVATION FROM THE SPONSOR PERSPECTIVE. OF THESE TRIALS, WHICH IS TO GET A TRIAL UP AND RUNNING THAT THEY CANNOT OTHERWISE OBTAIN FUNDING FOR IS ONE MOTIVATION. AS WE SAY THE GIST OF THE LARGER PARAGRAPH AND THE SECOND SHORTER PARAGRAPH IS TO SAY THAT ANOTHER POSSIBLE MOTIVATION MAYBE PROFIT SEEKING. WE KNOW IT APPEARS THAT SOME PAY TO PLAY TRIALS ARE NOT INTENDED TO GENERATE IMPORTANT SCIENTIFIC KNOWLEDGE BUT RATHER PRE-TEXT TO CIRCUMVENT REGULATORY PROHIBITIONS AGAINST MARKETING INVESTIGATIONAL PRODUCTS. >> WE DON'T HAVE TO WORD SMITH NOW BUT I THINK THE INDUSTRY MOTIVATION HAS TO BE NUANCED BETTER BECAUSE WANTING TO GET PAY TO PLAY WHERE YOU PAY FOR INVESTIGATIONAL DRUG IS NOT IN A SETTING WHERE YOU HAVE A SMALL STARTUP FOR EXAMPLE THAT CAN'T AFFORD COST OF THE DRUG, IS NOTHING TO DO WITH INTELLECTUAL PROPERTY SIZE OF PATIENT POOL, ET CETERA, SO I THINK IT'S -- DOESN'T QUITE FIT, THERE MAYBE A -- INVESTIGATOR MIGHT HAVE TO CHARGE FOR THE DRUG UNLESS THE INDUSTRY DONATES IT BUT THAT MAY COME DOWN TO WHETHER THEY ARE WILLING TO DONATE IT, ET CETERA SO WE DON'T HAVE TO WORD SMITH IT NOW BUT I DIDN'T THINK INDUSTRY MOTIVATION CAPTURED WHAT I WOULD THINK THE MOTIVATION WOULD BE OF AN INDUSTRY TO THEN ENGAGE IN PAY TO PLAY. THAT'S MY SENSE. YOU DON'T HAVE ENOUGH TIME TO CRAFT IT NOW. OTHERS. ALL RIGHT. THE, AFTER THAT WE HAVE SUBJECTS MOTIVATION FOR JOINING TO JOININGTRIALS OF THIS NATURE. THIS IS FAIRLY STRAIGHT FORWARD. THEN WE MOVE INTO REGULATORY ETHICAL ISSUES. WE START BY TALKING IN THE BACKGROUND WHAT IS IN THE DRUG DEVICE REGULATIONS WITH RESPECT TO PAYMENTS BY SUBJECTS TO PARTICIPATE. AND THE CHARGE FOR INVESTIGATIONAL DRUGS AND BIOLOGICS AND THE CHARGING FOR INVESTIGATIONAL DEVICES. AND THIS IS JUST REGULATORY LIFTED OUT OF THE REGULATIONS. PRETTY STRAIGHT FORWARD. THEN AFTER TALKING FDA WE KNOW NO OTHER U.S. REGULATIONS GOVERNING HUMAN SUBJECTS RESEARCH DIRECTLY ISSUE OF PAY TO PARTICIPATE THOUGH SOME OF THE CRITERIA FOR APPROVAL ARE RELEVANT AS ARE CERTAIN CONSENT REQUIREMENTS. SO THE THIS POINT WE SHIFT FROM THOSE REGULATORY CALL OUTS TO TALKING ABOUT ETHICAL PRINCIPLES AND WHAT CONSIDERATIONS IN THESE AREAS MAYBE STARTING WITH BENEFICENCE. QUESTIONS OR COMMENTS ON THIS SECTION? >> SANDY. >> COULD SOMEONE BE INDUCED TO TAKE PART IN PAY TO PLAY TRIAL IN PREFERENCE TO STANDARD OF CARE WHICH WOULD BE COVERED BY INSURANCE? DO WE NEED TO TALK ABOUT THE REQUIREMENTS THAT PEOPLE UNDERSTAND THE ALTERNATIVES TO THIS PAY TO PLAY TRIAL THEY HAVE BEEN MADE AWARE OF ALTERNATIVES A WE NORMALLY DO? >> CERTAINLY THERE'S AN EXPECTATION THE INFORMED CONSENT DOCUMENT IS GOING TO COVER ALTERNATIVES AND THAT THE IRB WOULD HAVE -- WOULD APPROVE THAT CONSENT DOCUMENT INCLUDING THE LANGUAGE DESCRIBING ALTERNATIVES TO PARTICIPATION RESEARCH BENEFIT BEYOND THAT, IT BECOMES POINT OF CONSENT PROCESS AND DISCUSSION LOOKS LIKE AND HOW THE -- THE POTENTIAL PARTICIPANT HAD THAT CONVERSATION WITH THE STUDY TEAM ABOUT WHAT THE ALTERNATIVES ARE AND WHY THE RESEARCH MAY OR MAY NOT BE APPROPRIATE FOR THEM. >> SHOULD THE IRB CONSIDER ALTERNATIVES WHEN THEY LOOK TO APPROVE THE PROJECT? IN OTHER WORDS, MIGHT THEY MAKE A JUDGMENT THIS IS ACTUALLY A TRIAL THAT'S DIRECTING PEOPLE AWAY FROM VIABLE ALTERNATIVES AND THEREFORE THEY DON'T WANT TO APPROVE IT BECAUSE THE RISK BENEFIT RATIO -- I DON'T KNOW IF SAY THIS PROPERLY. >> CRITERIA FOR APPROVAL. IF THEY THOUGHT THE RISKS WERE NOT REASONABLE IN RELATION TO ANTICIPATED BENEFITS THEY WON'T APPROVE IT ON THAT CRY TIERION T. >> SANDY, I THINK ONE OF THE CHALLENGES IS THERE ARE MULTIPLT FLAVORS TO THESE TYPES OF STUDIES. SO ONE WOULD BE IN THE -- IN DRUG AREA ORPHAN DRUG AREA, DIFFICULT TO SOLICIT FUNDING FROM A STANDARD MECHANISM BUT THEN THERE ARE ALSO I FEAR ALL SORTS OF QUACK THERAPIES THAT MAY BE FALL INTO THIS REALM AS WELL. SO THIS POINT IS VERY WELL TAKEN. IT'S ALLUDED TO IN THE SECTION ON INFORMED CONSENT BUT THERE IS A RISK FOR THERAPEUTIC MISCONCEPTIONS. >> MARY ELLEN. >> SORT OF A OVERARCHING ISSUE OR QUESTION. THE DOCUMENT ASSUMES THERE'S INFORMED CONSENT AND IRB REVIEW. BUT I THINK IT WAS SORT OF WHAT IT WAS POINTED OUT IN THE HOLLY FERNANDEZ AND JAFFE ARTICLE THAT THERE MIGHT BE SOME PAY TO PARTICIPATE TRIALS THAT LEGALLY COULD BE CONDUCTED WITHOUT HAVING IRB OVERSIGHT. IT JUST SEEMS TO BE A GAP THAT IS MISSING IN THIS PAPER BECAUSE IT IS ASSUMING EVERYTHING IS GOING TO HAVE OVERSIGHT. >> I THINK IT COULD BE ACKNOWLEDGED IN THIS PAPER. >> WE CAN'T ADDRESS THAT. >> THE MOST WE CAN DO IS CALL OUT AND SAY -- >> WATCH OUT. >> THEY ARE UNFUNDED AND ARE OTHERWISE SUBJECT TO FDA REGULATIONS BECAUSE THEY NOT A CLINICAL INVESTIGATION TECHNICALLY SPEAKING THERE IS NO REGULATORY REQUIREMENTS THAT ARE IMPOSED ON THAT TYPE OF RESEARCH. >> I THINK IT WOULD BE GOOD TO CALL THAT OUT. >> IF THEY DON'T PLAN TO PUBLISH AND DON'T PLAN TO APPLY FOR APPROVAL, IF YOU DON'T GET AN IRB APPROVAL OR FDA APPROVAL YOU PROBABLY CAN'T PUBLISH THIS IN A REASONABLE JOURNAL AND YOU CERTAINLY CAN'T APLAY FOR APPROVAL OF THE DRUG. >> MAKING MONEY AS CLINICAL MATTER YOU CAN DO WHATEVER YOU DAM WELL PLEASE. >> CORRECT. BUT THAT'S NOT NEW, THAT'S ALWAYS BEEN THE CASE. SO YES, IN THE BEGINNING OF THE DOCUMENT WE CAN CERTAINLY NOTE THAT THERE IS THIS REGULATORY GAP THAT SOMEBODY SOME OF THESE ACTIVITIES FALL INTO. IN THE BULK OF THIS DOCUMENT WE TALK WHAT HAPPENS WHEN IRB DOES GET THIS SORT OF THING. I DID A QUICK WORD SEARCH, ALTERNATIVE, DIDN'T FIND EQUIPMENT IN DOCUMENT, CERTAIN HI SOMEWHERE IN THIS SECTION OF WHEN WE GET TO THE RECOMMENDATIONS THAT WE PROBABLY OUGHT TO ADD SOMETHING IRBs SHOULD BE LOOKING AT THE ALTERNATIVES. AND MAKING A DETERMNATION, WHEN THERE ARE ALTERNATIVES SHAI SHOULD BE ADEQUATELY DESCRIBED IN THE CONSENT DOCUMENT. THAT'S PROBABLY AS FAR AS IRB COULD TAKE THAT PIECE OF IT. >> DAVID. NANCY CHAL HEDGED ME TO PROPOSE SOME LANGUAGE IN THE HOPES THAT WE CAN APPROVE THIS TODAY. CAN I READ WHAT I HAVE? YOU DON'T HAVE TO TYPE IT OUT AND SEE WHAT PEOPLE THINK. >> SURE. >> SO LINE 65 THROUGH 69 I WOULD DELETE THAT. I THINK UNPACKING THAT WOULD BE MUCH TOO COMPLICATED. SO ON THE INDUSTRY SIDE TO PROFITABLE SALE, I WOULD JUST DELETE THAT AND REPLACE IT WITH THIS H. ON THE INDUSTRY SIDE THE PRODUCTION COSTS OF AN INVESTIGATIONAL DRUG OR DEVICE MAYBE PROHIBITIVE TO CONDUCT OF CLINICAL TRIAL AB SEPTEMBER CHARGING CHARGING FOR INVESTIGATION ALG PRODUCT. A SPONSOR MAY OR MAY NOT WITH WILLING TO DONATE AN INVESTIGATIONAL PRODUCT TO INVESTIGATOR INITIATED TRIAL COMMA LEADING TO THE NEED FOR THE INVESTIGATOR TO CHARGE FOR PARTICIPATION IN A CLINICAL TRIAL. COUPLE OF EXAMPLES. >> THOSE OF US ONLINE OR LISTENING IN, CAN YOU PLEASE -- WHAT YOU ARE GOING TO DELETE? >> STARTS LINE 65 FROM ON THE INDUSTRY SIDE. CAN YOU SEE THE DOCUMENT OR NOT? >> I'M ON THE PHONE. >> SO BASICALLY FROM LINE 65, ON THE INDUSTRY SIDE THERE WAS LITTLE MOTIVATION TO FUND RESEARCH UNLIKELY TO GENERATE PROFIT, THAT'S TRUE AND UNRELATED THIS MAYBE ANTICIPATED FOR EXAMPLE MANY THE PRODUCT IN QUESTION NOT SUFFICIENTLY VALUABLE AS MATTER OF INTELLECTUAL PROPERTY INTEREST EXPIRED PATENTS AND EXCLUSIVE ITY ON PATENT SUBJECT MATTER OR SIZE POTENTIAL PATIENT POPULATION STOO SMALL TO SUSTAIN PROFITABLE SALE. I THINK WOULD BE TOO DIFFICULT TO UNPACK ALL THAT AND JUST TOO COMPLEX. SO SUGGESTING WE DELETE THAT AND GIVE THE FOLLOWING TWO EXAMPLES ON THE INDUSTRY SIDE THE PRODUCTION COSTS OF AN INVESTIGATIONAL DRUG OR DEVICE MAYBE PROHIBITIVE TO CONDUCT OF CLINICAL TRIAL OF A CLINICAL TRIAL ABSENT CHARGING FOR INVESTIGATIONAL PRODUCT. AND THAT LEADS TO THE FDA THING WHERE YOU CAN DO THAT. AND THEN SECOND SENTENCE WOULD BE A SPONSOR MAY OR MAY NOT BE WILLING TO DONATE AN INVESTIGATIONAL PRODUCT TO INVESTIGATOR INITIATED TRIAL COMMA, LEADING TO THE NEED FOR THE INVESTIGATOR TO CHARGE FOR A PARTICIPATION IN THE CLINICAL TRIAL. MAY OR MAY NOT. YOU COULD SAY MAY NOT, THAT'S FINE. MAY NOT BE WILLING WHICH IS SINCE WE ARE TALKING CHARGING PEOPLE, SPONSOR MAY NOT BE WILLING TO DONATE ET CETERA. SO I DON'T KNOW -- I DON'T GET A VOTE. >> WALTER, MY QUESTION IS HOW DO YOU FEEL ABOUT THAT. MARY ELLEN, AS OTHER INDUSTRY PEOPLE. >> DIRECTIONALLY I LIKE IT, I THINK IT STARTS WITH PRODUCTION COSTS, IT'S NOT REALLY PRODUCTION, IT'S DEVELOPMENT COSTS. >> FINE WITH DEVELOPMENT COSTS. >> I LAKE YOUR SUGGESTION. I THOUGHT IT WAS A -- I LIKE YOUR SUGGESTION. PARTS OF THAT WERE A LITTLE HARSH ON INDUSTRY, SPECIFICALLY THE LATTER WHEN YOU ARE TALKING ABOUT SMALL POPULATIONS, MANY COMPANIES ARE SPENDING A LOT OF MONEY INTO RARE PEDIATRIC DISEASES. >> THAT'S WHY I THINK IT WOULD BE TOO COMPLICATED TO TRY TO MUCK -- >> JUST DELETING THAT. >> YEAH. >> ALL RIGHT. I CAN GET THOSE EXACT WORDS FROM YOU LATER SINCE I KNOW YOU HAVE THEM SCRATCHED OUT. >> I'LL HAND IT TO NANCY NOW. >> DOES ANYONE OBJECT TO THAT? ANYBODY OBJECT TO THAT OR WANT TO FURTHER AMEND IT? I WILL QUICKLY MOVE ON BEFORE SOMEBODY RECONSIDERS. I WILL GO BACK DOWN TO I THINK WE WERE ON THE JUSTICE SECTION. YES. >> I THINK THIS IS VERY WELL WRITTEN AND REALLY CAPTURES THE SALIENCE OF THE IMPORTANCE OF LEAVING PEOPLE OUT AS WELL AS THE PROBLEM WITH SCIENTIFIC VALIDITY, I THINK WE ARE REALLY ONLY INCLUDING PEOPLE WHO CAN AFFORD TO PAY. I THINK WE DON'T KNOW WHAT THE COST OF PAY IS. I THINK THERE CERTAINLY COULD BE IF IT'S MODEST THAT MIGHT NOT BE MUCH ISSUE BUT IF WE ARE TALKING NOW REALLY HUNDREDS OF THOUSANDS OF DOLLARS THAT SUBSTANTIALLY CHANGES THE GROUP. THE ONE MAYBE SLIGHT CHANGE I WOULD MAKE IN 175 IS WHERE I AM 176, ARE THOSE WHO ARE ECONOMICALLY ADVANTAGED ENOUGH TO PAY THE COST OF PARTICIPATION SUFFICIENTLY BIOLOGICALLY AND CLINICALLY DIVERSE? IF THERE IS A WAY TO ADD IN -- IF THEY ARE ACTUALLY REPRESENTATIVE OF THE POPULATION OF PEOPLE WHO HAVE THE CONDITION. I THINK THAT'S -- I DON'T KNOW HOW YOU KNOW IF PEOPLE ARE BIOLOGICALLY AND CLINICALLY DIVERSE IN THAT. BUT ARE PEOPLE -- ARE THE PEOPLE WHO ARE GOING TO PARTICIPATE REALLY REPRESENTATIVE OF FOLKS WHO HAVE THE DISEASE? >> THIS IS JANET. IN RURAL POPULATIONS IN CLINICAL TRIALS, WE ARE NOT REPRESENTATIVES. THAT'S PRETTY STANDARD ACTUALLY. I'M NOT SURE THAT SHOULD BE A REASON FOR IRB TO DISREGARDED THIS. >> BUT YOU ARE REPRESENTATIVE OF THE STUDY POPULATION, NOT MEANT TO BE REPRESENTATIVE OF GENERAL POPULATION. >> NOT REPRESENTATIVE OF PEOPLE WITH THE CONDITION. WHEN YOU HAVE A RARE -- THESE RARE GENOMIC TRIALS MIGHT BE OFFERED IN TWO OR THREE LOCATIONS IN THE WORLD. YOU ARE GOING TO ONLY GET THE PEOPLE WHO HAVE THE RESOURCES AND TIME TO BE ABLE TO GO TO THOSE PLACES AND PARTICIPATE IN THE TRIALS. THAT IS -- THEY ARE NOT GOING TO BE REPRESENTATIVE OF ALL THE PEOPLE WHO HAVE LUNG CANCER WITH THAT MUTATION. >> THAT IS ANOTHER CONVERSATION. I STILL STAND BY THAT FROM A SIESK STANDPOINT. WHAT I'M ADDING THOUGH IS NO DIFFERENT THAN WHAT'S ALREADY INCLUDED WHICH IS, IS THE GROUP SUFFICIENTLY BUY LONLICALLY AND CLINICALLY DIVERSE, THAT IS ALREADY IN THE LANGUAGE. IF WE ARE SAYING THAT THAT'S APPROPRIATE, THAT'S ALSO SAYING THAT THOSE STUDIES WHO ONLY INCLUDE PEOPLE WHO HAVE THE RESOURCES TO PARTICIPATE THAT THEY ARE CHALLENGES WITH THE SCIENTIFIC VALIDITY OF THAT. >> JANET, LET ME RESPOND AS WELL. IN TARGETED THERAPY, WHAT IT COMES DOWN TO WHAT OTHER RELEVANT CHARACTERISTICS OF THE POPULATION ON WHICH YOU NEED TO EVALUATE WHETHER THEY ARE TRULY REPRESENTATIVE OR NOT. IF YOU HAVE GOT A HIGHLY TARGETED THERAPY TO A SMALL POPULATION TO WHERE YOU HIT THAT TARGET THEY RESPOND I WOULD ARGUE PROBABLY THE PRESENCE OF THE TARGET IS SUFFICIENT TO DECIDE IF THAT POPULATION IS REPRESENTED SO IT'S NOT INTENDING TO SAY THAT YOU NEED TO THEN BE REPRESENTED ALONG ALL THE OTHER CHARACTERISTICS FROM A SCIENTIFIC AND CLINICAL PERSPECTIVE. >> SO EVEN THOUGH WE MIGHT HAVE THE REARRANGEMENT IN THE CASE OF (INDISCERNIBLE) ELK WE HAVE -- THERE ARE 21 DIFFERENT GENES THAT WE KNOW OF CURRENTLY THAT WILL PAIR WITH ROSS 1. ALL THE DRUGS WERE DEVELOPED ON THE BASIS OF ONE PAIRING PARTNER. IT'S NOT REPRESENTATIVE OF IT STILL HAS RESULTED IN A DRUG THAT MAKES A DIFFERENCE. I'M JUST SAYING THAT WAS SOMETHING THAT I WAS GOING TO HAVE A COMMENT ABOUT IN THE DOCUMENT IS THAT I'M NOT SURE IT'S VALID TO SAY SIMPLY BECAUSE THE POPULATION IS NOT REPRESENTATIVE EVERYONE WITH THE DISEASE THAT THAT NECESSARILY MAKES IT SCIENTIFICALLY INVALID. IF IT GIVES YOU A CHANCE TO STUDY WHETHER OR NOT THAT INTERVENTION WORKS AT ALL. >> I HAVE A WORD SMITHING SOLUTION THAT I HOPE WILL BYPASS THIS, THIS IS IMPORTANT AND NUANCED. BUT I THINK WE COULD SIMPLIFY IT BECAUSE EVERY STUDY IS GOING TO RAISE DIFFERENT KINDS OF ISSUES FOR IRBs AROUND THESE POINTS. SO I PROPOSE THAT WE CHANGE SUFFICIENTLY BIOLOGICALLY AND CLINICALLY DIVERSE TO SUFFICIENTLY REPRESENTATIVE AND DI VERSE THEN WE CAN APPLY WHATEVER ADDITIONAL TERMINOLOGY IS APPROPRIATE FOR THE IRB IN WHATEVER SITUATION IS AT ISSUE. >> THAT'S WHAT IT WOULD LOOK LIKE. >> CAN YOU READ IT AGAIN? >> THE EDITS TO WHAT NOW -- ARE THOSE WHO ARE ECONOMICALLY ADVANTAGED ENOUGH TO PAY COSTS OF PARTICIPATION SUFFICIENTLY REPRESENTATIVE AND DIVERSE? >> I CAN ACCEPT THAT. >> OKAY. GOOD. YES. OTHER COMMENTS ON THIS SECTION? ALL RIGHT. WE WILL MOVE TO AUTONOMY AND INFORMED CONCEPT. I'M MAKING SURE I -- SANDY, THIS SECTION IS WHERE I CAN TRY TO COME UP WITH A SENTENCE QUICKLY BUT I THINK WE DON'T NEED TO ADD MORE THAN A SENTENCE REMINDING OF THE OBLIGATION OF THE CONSENT HAS TO UNCOLLUDE DESCRIPTION OF THE AVAILABLE ALTERNATIVES AND WE JUST LIFT IT FROM THE REGULATORY LANGUAGE. >> I THINK WE CAN IF WE KNOW PRETTY MUCH WHAT THAT SENTENCE IS GOING TO SAY, WE CAN APPROVE IT WITH THAT MODIFICATION T. >> YEAH. YES. GLZ WANTED TO DO THIS TRIAL I THINK IT WOULD BE WORTH THROWING -- WORTH FILLING OUT THE PAPER WORK AND SEEING IF I CAN GET AN IRB THE APPROVE IT. AND IF I COULDN'T GET ONE IRB TO APPROVE IT I COULD TRY ANOTHER IRB. THERE NOTHING TO PREHAVEN'T ME FROM DOING THAT AND NO REQUIREMENT TO DISCLOSE ANOTHER IRB HAS TURNED YOU DOWN. >> I DON'T THINK THERE'S REQUIREMENT, I KNOW MANY IRBs WILL ASK, CAN'T SPEAK FOR ALL IRBs BUT IT'S NOT UNCOMMON. RIGHT. >> INVESTIGATORS ARE FORBIDDEN TO DO THAT, THE REALITY IS IF THIS IS INVESTIGATOR INITIATED UNLESS AFFILIATED WITH ANY INSTITUTION THAT PROBABLY THAT'S NOT AN OPTION. INDEPENDENT I RB ALREADY ASKED THAT QUESTION AS PART OF THEIR SUBMISSION PROCESS. >> IT'S ALSO JUST PART OF -- WE ONLY HAVE SO MUCH CONTROL. I THINK -- SPONSOR AND THE IRB WHATEVER THEY SELECT ARE IN CAHOOTSTO MAKE A PROFIT OFF THIS WE CAN'T SKIP A LOT. >> WALTER. >> SO THE NUMBERS CHANGED A LITTLE BIT GIVEN ADDITION. BUT LINE 238 RIGHT THERE BENEFITS OUTWEIGH CHANGE OUTWEIGH TO JUSTIFY THAT WAY IMPLY IT IS BENEFITS NEED TO BE GREATER THAN -- >> I AGREE. >> >> WALTER. >> IT'S A QUESTION ABOUT THE REMIT OF THE COMMITTEE. I HAVE THE SAME CONCERN AS SANDY RAISED, WHICH IS ACKNOWLEDGE PAPER BY LYNCH AND J AFFE, THAT SOME STUDIES CAN BE OUTSIDE OF IRB OVERSIGHT. WONDER WHETHER THIS -- INSOFAR AS COMMITTEE LOOKED TO FOR ETHICAL GUIDANCE FOR FEDERALLY REGULATED RESEARCH, ARE WE ABLE TO ACKNOWLEDGE SOME OF THESE STUDIES WILL BE OUTSIDE OF -- OUTSIDE OF IRB OVERSIGHT? >> WE CAN ABSOLUTELY ACKNOWLEDGE IT. I THINK IN OUR ROLE MAKING RECOMMENDATIONS TO OHRP FOR GUIDANCE, SENSE OHRP HAS NO AUTHORITY BUT THAT'S OKAY. WE HAVE TALKED ABOUT SOME OTHER THINGS THAT FALL OUTSIDE THE REGULATORY AUTHORITY. SO MAYBE WE COULD ADD A SENTENCE SOMEWHERE, NOT SURE WHERE, THAT SAYS THAT SACHRP ACKNOWLEDGES MANY SUCH TRIALS MAY NOT BE REQUIRED THEN TO UNDERGO I RKSB REVIEW BY REGULATIONS. THE COMMITTEE FELT STRONGLY SOME REVIEW THAT FOLLOWS THESE PRINCIPLES SHOULD BE REQUIRED AND MAYBE IN THE QUESTIONS THAT ASK THAT NIH ASKED US TO PROVIDE PARTICIPANTS SHOULD ASK WE COULD SAY HAS THIS TRIAL BEEN REVIEWED BY AN IRB, WE COULD ADD THAT. >> THAT WOULD BE HELPFUL, STEVEN, THAT WOULD BE MY SUGGESTION BECAUSE I AM CONCERNED SOME OF THESE STUDIES MAY ACTUALLY BE EXPLOITIVE. >> THAT IS CAPTURED IN FIRST ONE OF THE QUESTIONS WHO REVIEWED THIS TRIAL AND SAID OKAY. DO YOU HAVE A PLACE YOU THINK WE SHOULD PUT THE ACKNOWLEDGMENT THAT SOME STUDIES ARE NOT GOING TO REQUIRE -- >> SHOULD HAVE IT ANYWAY. >> A LOGICAL PLACE TO PUT IT OR PLACE IT COULD FIT IS SECTION ON BENEFICENCE NO U.S. REGULATIONS ADDRESSING PAY TO PLAY PARTICIPANT TRIALS COULD ADD ANOTHER PARAGRAPH ACKNOWLEDGE THERE'S ALSO -- THERE WILL BE STUDIES THAT ARE UNREGULATED BECAUSE THEY ARE NOT FEDERALLY FUNDED NOR DO THEY -- NOR SUBJECT TO FDA REGULATION. >> SO WE MIGHT SAID THAT WOULD BE GOOD WE MIGHT EVEN SAY CREDIBLE STUDIES SACHRP WOULD ENCOURAGE INVESTIGATORS PLANNING CREDIBLE STUDIES THAT CHARGE PARTICIPANTS AND DON'T REQUIRE REGULATORY REVIEW TO SUBMIT THEIR STUDIES VOLUNTARILY FOR REVIEW OR FIND SOMEBODY -- THE LANGUAGE IS NOT GREAT. >> DELETE THE WORD CREDIBLE THAT'S FINE, THE ONES THAT AREN'T CREDIBLE TO GO THERE TOO. >> GOOD CATCH. >> THIS IS GENERALLY TRUE, IT'S NOT ONLY PAY TO PLAY STUDIES THAT WOULDN'T NECESSARILY -- AS A GENERAL STATEMENT WE KNOW SOME RESEARCH FALLS OUTSIDE OF THE SCOPE OF REQUIRED REVIEW AND AS WITH ANY OTHER STUDY WE WOULD ENCOURAGE INVESTIGATORS TO SEEK REVIEW VOLUNTARILY. >> WE CAN EVEN SAY BECAUSE OF THE PARTICULAR SIXER OF PAY TO PLAY SO THAT WE ARE NOT MAKING A GENERAL STATEMENT. >> I STARTED HERE. I THINK WE GOT THE START OF IT, JUST A MATTER OF HOW MUCH MORE WE WANT TO SAY. SO I THINK IT'S NICE TO SET AN EXPECTATION FOR BEST PRACTICE. THE CI BELIEVES THAT COMMA, BECAUSE OF THE PARTICULAR ISSUE Z RAISED BY TRIALS THAT REQUIRE PARTICIPANTS TO PAY, SUCH TRIALS SHOULD BE VOLUNTARILY SUBMITTED FOR REVIEW IRB OR EQUIVALENT BODY. (OFF MIC) >> I CAN TYPE BETTER THAN THIS BUT THIS IS NOT MY KEYBOARD. >> MAYBE FOR DISCUSSION ANOTHER DAY. I DO THINK THAT THERE IS A COMMON PERCEPTION AMONG THE PUBLIC THAT ANY RESEARCH INVOLVING HUMANS DOES INVOLVE SOME OVERSIGHT. I KNOW WE ARE MAKING THE DISTINCTION HERE THAT BECAUSE THERE'S SPECIFIC ISSUES RAISED WITH THE PAY TO PARTICIPATE BUT THE DOCUMENT REFERENCE IS TRUST IN SCIENCE AND I DO THINK THAT WE HAVE TAKEN MANY PEOPLE HAVE TAKEN GREAT LENGTHS TO SAY THAT RESEARCH HAS CHANGED AND THERE ARE PROTECTIONS IN PLACE. WE SAY THAT PRETTY BROADLY. NOT JUST FOR RESEARCH PAID FOR CONDUCTED, BY WITH RESOURCES FROM FEDERAL GOVERNMENT. >> HOLD THAT THOUGHT. THAT'S THE GIST OF THE TWO PARTS OF THE UNCHECK THE BOX PART LOOKS ALL THIS STUFF WITH THAT OVERSIGHT. SO I DON'T KNOW WHAT WE ARE GOING TO DO ABOUT THAT OR HOW TO APPROACH IT BUT I AGREE. >> SO I WILL JUMP BACK DOWN TO THE RECOMMENDATIONS. WE HAD A SUGGESTED WORD CHANGE FOR NUMBER ONE. FOR NUMBER 2 QUESTION WAS THE RISK BENEFIT BALANCE ACCEPTABLE? (OFF MIC) >> IT WAS BUT THE SAME ISSUE THOUGH. >> MAYBE YOU HAVE TO SAY JUSTIFIABLE. >> THEN QUESTIONING WHY TRADITIONAL FUNDING SOURCES ARE NOT BEING USED. WILL REQUIRE PAYMENT INFLUENCE EQUITABLE SUBJECTS SELECTION. WE GOT A LONGER SECTION ABOUT THERAPEUTIC MISCON SEPTION. >> THIS MIGHT BE A PLACE TO SAY ALSO COVERING THE SAME GROUND THAT ONE WAY TO MITIGATE THAT IS TO MAKE SURE THAT THE ALTERNATIVES ARE ADEQUATELY EXPLAINED. >> THAT MAY FIT INTOP THIS BULLETED LIST. >> MY SUGGESTION WOULD BE TO PUT IT IN THE ACTUALLY ADD IT TO THE SECOND TO LAST BULLET. IN THE PARENTHETICAL EXAMPLE ASKING REFLECTION ABOUT THE POSSIBILITY THE INTERVENTION MAY HAVE NO BENEFICIAL EFFECTS OR BE HARMFUL OR THAT ALTERNATIVE TREATMENTS MAY BE A BETTER CHOICE. OR MAYBE PREFERABLE. >> ALL RIGHT. THEN WE HAVE A CONCLUDING SECTION ON QUESTIONS POTENTIAL SUBJECTS SHOULD CONSIDER ASKING ABOUT PAY TO PARTICIPATE TRIALS. . I'M SORRY. THIS IS WHERE WE ACTUALLY DON'T ADVISE PARTICIPANTS TO ASK IF IRB REVUED THE STUDY, IT WOULD FIT INTO THIS FIRST BULLET THOUGH. OKAY. >> DAVID I WONDER WHETHER WE NEED TO BE MORE EXPANSIVE IN TERMS OF WHAT EXACTLY WILL I BE PAYING FOR. INDIVIDUALS MAY THINK THEY ARE PAYING FOR THE COST OF THE THERAPEUTIC INTERVENTION BUT MAY NOT RECOGNIZE THEY MAY BE PAYING FOR DIAGNOSTICS AS WELL. >> SO WHAT DID YOU DO STAY WITH PARENTHETICAL LISTING EXAMPLES OF MORE GENERAL QUESTION, WILL MY HEALTH INSURANCE COVER THE COST OF PARTICIPATION IN ANYWAY. >> DON'T CALL THE STUDY TREATMENT CALL IT THE STUDY INTERVENTION. >> THE FIRST BULLET RATHER THAN SAYING IRB REVIEWED IT MOST WON'T, WE CAN SAY AS AN ETHICAL REVIEW, AND SCIENTIFIC REVIEW, IF WE WANT TO SPECIFY SOMETHING BECAUSE THAT MIGHT BE MORE MEANINGFUL TO PEOPLE WHO DON'T KNOW WHAT AN IRB IS WHICH IS WHAT THIS IS IS GEARED TOWARDS. >> YOU CAN BE ASSURED PEOPLE WHO ARE PROMOTING RESEARCH REVIEWED THE RESEARCH. >> OTHER QUESTIONS WE ARE MISSING IFNY? MARY ELLEN. >> LINE 348 WHEN WILL I BE EXPECTEDDED TO PAY, THERE WAS A REFERENCE EARLIER ABOUT IT COULD BE LUMP SUM OR INSTALLED. I WOULD ASK IF IT'S INSTALLMENT PAYMENT WHAT HAPPENS IF I MISS PAYMENT. (OFF MIC) >> GET MONEY BACK. >> GOING ONCE. >> IT'S A WORD SMITHING BACK TO LINE 35 FIRST PAGE. WITH OF COURSE WITH THE ETHICAL STANDARDS NORMALLY APPLIED BY THE REGULATED RESEARCH COMMUNITY, BECAUSE THERE'S A LOT OF REGULATED COMMUNITIES. REGULATED RESEARCH COMMUNITY. IS THERE ANY CHANCE OF PARTICIPATING IN THIS COULD MAKE IT IMPOSSIBLE FOR THEM TO GET ANY CONVENTIONAL TREATMENT OR NOT PARTICIPATE IN A CLINICAL TRIAL REGULAR CLINICAL TRIAL? COULD THEY GIVE UP THE RIGHTS TO DO THINGS THAT ARE IMPORTANT TO THEM BY PARTICIPATING IN THIS? I DON'T KNOW WHAT I WOULD NEED TO SAY THAT. >> THAT'S AN IMPLICATION OF WHAT ARE SOME OF THE REASONS I MIGHT NOT BE WILLING TO JOIN THE RESEARCH. IT'S NOT GOING -- IT'S NOT GOING TO BE AN ISSUE FOR EVERY SINGLE TRIAL AND THIS IS INTENDED REALLY TO BE A GENERAL LIST. THIS -- THESE ARE QUESTIONS THAT THEY ARE ASKING OF OF THE PEOPLE RUNNING THE TRIAL BUT ALSO THERE ARE POTENTIAL QUESTIONS FOR THE IRB BECAUSE THIS IS IN THE CONTEXT OF QUESTIONS POTENTIAL SUBJECTS SHOULD ASK IRB ABOUT IRB REGULATED RESEARCH THAT'S BEEN APPROVED. THIS ISN'T ABOUT RESEARCH THAT FALLS OUTSIDE THE IRB PURVIEW. >> THAT IS FAIR BUT I THINK WE WERE JUST ASKED THE QUESTION WHAT SHOULD PARTICIPANTS ASK WHEN FACED WITH -- I MEAN THEY WON'T NECESSARILY KNOW WHETHER OR NOT IT'S BEEN IRB REVIEWED. >> THE LEAD IN TO THE LIST OF QUESTIONS SAYS IT'S STARTING POINT FOR IRB INVESTIGATOR SPONSORS BUT THESE ARE WRITTEN FROM PERSPECTIVE OF POTENTIAL PARTICIPANT WHAT SHOULD THEY BE ASKING. >> THEY ARE REALLY INTENDED TO BE VERY SPECIFIC TO WHAT ARE QUESTIONS THAT ARE GOING TO COME UP IN PAY TO PLAY RESEARCH BECAUSE THE OTHER LIST OF QUESTIONS REFERENCED ARE FOR ANY RESEARCH. SANDY'S QUESTION IS ACTUALLY A REALLY GOOD ONE BUT IT IS NOT ONE THAT'S ONLY GOING TO COME UP IN PAY TO PLAY CIRCUMSTANCES. >> THAT'S A QUESTION WE CAME UP WITH IN OUR KEY INFORMATION RECOMMENDATIONS BACK WHENEVER THAT WAS LAST YEAR. I HAVE A MINOR STYLISTIC CHANGE IN LINE 85. IF WE ARE DONE WITH EVERYONE ELSE. NOT SURE IF SHE SAYS THIS IS TRUE HOW TO EXPLAIN POTENTIAL SUBJECTS KEY, THIS IS TRUE FOR RESEARCH AND HEIGHTENED WHEN SUBJECT CHARGE FOR PARTICIPATION. NOT SURE HEIGHTENED WORKS BUT IS MORE CRITICAL IS WHAT WE ARE TRYING TO CAPTURE. I THINK YOU CAN'T BE -- YOU CAN'T HEIGHTEN AND BE A KEY. >> WORKS FOR ME. >> I THINK WE ARE THERE THEN. >> SO MOVED. >> SECOND. THANK YOU. ALL IN FAVOR OF APPROVAL SAY AYE. >> AYE. >> OPPOSED. ABSTAINING. MOTION PASSES. THANK YOU. >> SO WE HAVE ACTUALLY WE ARE LATE FOR PUB LUCK COMMENT. DO WE HAVE ANY PUBLIC COMMENT? WE HAVE NO PUBLIC COMMENT. ANY COMMENTS FROM IN HOUSE AUDIENCE? ALL RIGHT. THANK YOU. THEN I WOULD ENTERTAIN A MOTION TO ADJOURN. MOVE TO ADJOURN. SECOND. JULIA, AM I FORGETTERRING ANYTHING? ALL IN FAVOR OF ADJOURNMENT SAY AYE. MOTION PASSES THANK YOU ALL.