Afternoon Speakers Q&A Panel

AT THE MICROPHONE, PLEASE. THESE ARE THE FANTASTIC TALKS.
I WANTED TO THANK YOU ALL FOR WHAT YOU HAVE DONE.
AND I WANT TO TALK A LITTLE BIT ABOUT THE BUGS THAT ARE STILL
HIDING UNDER THE ROCKS. FIRST, I THINK IT'S TOUGH FOR
ALL OF US TO ASK QUESTIONS AT THE END WITHOUT HAVING BEEN ABLE
TO ADDRESS YOU ONE AT A TIME. I HAD QUESTIONS THAT I FORGOTTEN
ALREADY. BUT I REMEMBER SOME OF THEM AND
I WILL ASK THEM. FIRST I BELONG TO AN IRB FOR A
LONGER TIME THAN I CAN RECALL, BEFORE THE IRBs WERE EVEN
CONSTITUTED. AND IT'S VERY DIFFICULT FOR EACH
ONE TO COME UP WITH A POLICY. I PERSONALLY BELIEVE THERE
SHOULD BE AN NIH-WIDE POLICY IN THESE AREAS THAT IRBs CAN
HANDLE. A COMPLIMENTED THE GENOME
INSTITUTE FOR COMING UP WITH POLICY POSITIONS HANDED OUT TO
THE IRBs FOR EACH IRB TO THINK ABOUT.
BUT STILL YOU DON'T KNOW WHAT THE IRB WILL DO WITH IT.
THAT'S ONE PROBLEM. ANOTHER PROBLEM IS THAT A LOT OF
MEMBERS OF THE IRB ARE IGNORANT ABOUT WHAT IS GOING ON.
I HAVE TO ARGUE WITH MY IRB ALL THE TIME BECAUSE MANY OF THE
MEMBERS ARE THE BRIGHT ONES BELIEVE THAT THERE ARE WAYS THAT
ONE CAN ONLY SELECTIVELY EXTRACT THE INFORMATION FROM WHOLE
GENOME SEQUENCING THEY WANT. AND THERE IS INFORMATION THAT
CAN BE IGNORED, THAT IT'S NOT EVEN THERE OR SEEN.
I'M UPSET WITH MY IRB BECAUSE I DON'T THINK THAT IS TRUE.
I THINK THE INFORMATION IS THERE.
CAN CAN'T BE HIDDEN AND PEOPLE ARE KIDDING THEMSELVES IF THEY
CAN TAKE IT OUT SELECTIVELY. I HAD ANOTHER COMMENT AND HAVE
ALREADY FORGOTTEN IT. LET ME JUST THINK FOR A MOMENT.
WHY DON'T WE GET SOME ANSWERS FIRST.
>> I THINK THAT'S ONE FOR ME TO TAKE.
SO I THINK YOU'RE HITTING ON TWO VERY IMPORTANT POINTS THERE THAT
IT WOULD BE USEFUL TO HAVE RESOURCES OR POLICIES OR SOME
MORE UNIFORMED TOOLS THAT ACROSS THE NIH WOULD BE AVAILABLE TO
INVESTIGATORS SO THEY CAN KNOW HOW BETTER TO ANTICIPATE WHAT IS
GOING TO BE EXPECTED OF THEM AT THE IRB AND I AGREE WITH THAT.
I THINK THERE IS A BALANCE BETWEEN GIVING IRBs THE
LATITUDE TO HAVE FLEXIBILITY TO CONSIDER THE PARTICULARS OF THE
A GIVEN STUDY AND THAT'S THE CONCEPT BEHIND THE SYSTEM TO
HAVE EACH INSTITUTION TO HAVE ITS OWN BOARD THAT CAN CONSIDER
LOCAL FACTORS. >> AT THE SAME TIME THE CONSENT
FORM HAS A BOILERPLATE ON IT. >> AND SO I WAS GOING TO --
I AGREE ON ANTICIPATING WHAT YOU'RE GOING TO SAY AND I DIDN'T
MEAN TO CUT YOU OFF. BUT IF WE COULD DEVELOP TOOLS
AND TEMPLATES AND EXAMPLES OF LANGUAGE BEEN APPROVED BY THE
IRB, THOSE ARE SOME GOALS. I FORGOT TO MENTION IN MY TALK.
THERE IS AN ENTITY SPRINGING UP ACROSS INSTITUTES AT THE NIH,
KNOWN AS PROTOCOL SERVICE CENTRES.
THE IDEA AND WE ARE WORKING VERY CLOSELY WITH THE NEW ONE FORMED
WITHIN NHGRI. THIS IS ANOTHER ENTITY CREATED
TO HELP SUPPORT CLINICAL RESEARCHERS AND DEVELOP
PROTOCOLS WITH THE IRB WE ARE IN CLOSE COMMUNICATION IN HOPES OF
DEVELOPING THESE KINDS OF TOOLS AND HELPING THEM HELP
INVESTIGATORS ANTICIPATE WHAT THE IRB MIGHT BE LOOK FIGURE AND
ARE HELP THEM RESPOND. AND I THINK I'M OPTIMISTIC THESE
RESOURCES WILL BE FORTHCOMING BUT AT THE SAME TIME I THINK
THERE IS A PROBLEM WITH ASSUMING WE CAN HAVE A WONG SIZE FITS ALL
APPROACH THAT WILL WORK IN ALL CIRCUMSTANCES SO THE TOOLS HAVE
TO BE INTERACTIVE AND FLEXIBLE AND THIS IS CHALLENGING AND
TAKES TIME. THE SECOND POINT I DIDN'T WANT
TO LOSE TRACK OF IS THE IDEA OF IRB TRAINING.
I THINK THAT'S A VERY VALID POINT.
THESE ARE COMPLEX ISSUES IN OUR OWN SPECIALIZED IRB WHERE WE ARE
FAMILIAR WITH GENETICS, WE EVOLVED IN OUR THINKING AND THIS
IS WHY WE HAVE DONE ADDITIONAL TRAINING.
WE HAVE DEDICATED OUR RETREATS TO INVITING INVESTIGATORS TO
TALK TO US ABOUT THE REALITIES SO IT'S BEEN A GIVE-AND-TAKE AND
I WOULD ENCOURAGE OTHERS TO CONSIDER WAYS TO BRING THEIR
MEMBERS UP TO SPEED AND THE STANDARDIZED TRAINING THEY
RECEIVE, THE REQUIRED TRAINING ISN'T REALLY GOING TO BE ROBUST
ENOUGH TO GET INTO THESE NUANCES.
I AGREE THAT THAT IS A PROBLEM AND SOMETHING WE SHOULD PAY
ATTENTION TO. >> SO I CAN COME UP WITH A THIRD
PROBLEM AND IT'S ONE THAT WASN'T EXISTING TODAY AND PROBABLY FOR
GOOD REASON. AND THAT THE NASTY SUBJECT OF
DIRECT TO CONSUMER TESTING. THIS IS GOING ON IN THE GENOME
FIELD, FDA AND OTHER AGENCIES HAVE SO FAR STUCK THEIR HEAD IN
THE GROUND BUT PATIENTS THINK THEY CAN BY PASS THE PHYSICIANS
AND THE COMPANIES THINK THEY CAN DO IT.
SOME HAVE PANELS THAT ARE SUPPOSED TO BE CONSTITUTED.
THIS IS UNREGULATED. SO I'D LIKE COMMENTS ON THAT.
WE BOTH HAVE SOME RELATED COMMENTS.
THIS HAPPENS TO BE AN AREA THAT I HAVE CARVED OUT AND THOUGHT OF
IT SEPARATE FROM WHAT WE ARE TALKING ABOUT TODAY BUT THEN I
WORKED ON IT AND CARE VERY MUCH ABOUT.
IN AN EFFORT TO CARE ABOUT WHAT WE HAVE BEEN TALKING ABOUT, I'LL
SAY TWO THINGS. FIRST, WE MAKE DARN SURE THAT
OUR PROTOCOLS AREN'T OFFERING SERVICES --
LET ME PUT TO THE A DIFFERENT WAY AND MUCH MORE POLITELY, I
THINK. SOME SUBJECTS MIGHT REQUEST TO
RECEIVE ALL OF THE RESULTS ON A DISK.
SOME INVESTIGATORS WITH THE BEST OF INTENTIONS AND WANTING TO
MEET MR. SUBJECT'SECTITATIONS HAVE TALKED TO IRBs AND WE
DON'T ALLOW THAT BECAUSE WE DON'T THANK GENOMIC INFORMATION
ON THAT SCALE IS READY FOR PRIME-TIME.
THERE IS NO WAY TO CERTIFY AN ENTIRE GENOME TEST.
I MIGHT BE WRONG ABOUT THAT. BUT WE REALLY CARE ABOUT THE
KINDS OF CAREFUL INTERPRETATION AND CONSIDERATIONS THAT WAS
TALKED ABOUT. WHEREAT RESEARCH DIFFERENTLY
THAN THOSE THAT MAKES THINGS AVAILABLE TO PEOPLE AT A PRICE
THAT SOME CAN AFFORD AND SOME CAN'T.
ONCE PEOPLE KNOW THESE ARE AVAILABLE, THEY MIGHT BE WANTING
TO ENROLL IF TRIALS THAT HELP US LEARN HOW MANY CERTAIN THINGS
HOW THIS WILL PLAY OUT IN CLINICAL PRACTICE.
I FLAG THAT AS A CONCERN I'M AWARE OF THAT BEARS BEARS ON THE
RESEARCH CONTEXT THAT IRBs AREN'T NECESSARILY POSITIONED
FROM THE INSIDE TO DEAL WITH. I THINK ISSUES OF REGULATION,
THEY ARE WAYS TO GO ABOUT DOING IT.
>> THE ONLY THING I'D ADD IS THIS IS PART OF THE REASON WHY
WE HAVE INCORPORATED SOCIAL AND BEHAVIORAL RESEARCH TO TRY TO
UNDERSTAND THE OCTOBERUAL CHOICE THAT IS PARTICIPANTS MAKE, THE
MEETINGS THEY ATTRIBUTE TO THE KINDS OF RESULTS WE COULD FIND
AND HOW THOSE CHOICES ACTUALLY PLAY OUT IN TERMS OF THEIR
ACTUAL BEHAVIORS ABOUT WHAT RESULTS THEY LIKE TO RECEIVE
BECAUSE IT IS REALLY HARD TO PREDICT THE UPTAKE OF THESE
KINDS OF TESTS AND WHAT PEOPLE ARE GOING TO DO WITH THE
INFORMATION AND HOW THEY ARE GOING TO APPROACH THE CLINICIANS
WITH THE INFORMATION. THAT'S WHY WE HAVE BUILT THESE
PROCEDURES IN THESE LABOR-INTENSIVE PROCEDURES INTO
INTO OUR PROTOCOLS TO TRY TO UNDERSTAND MORE ABOUT WHAT
PEOPLE ARE BRINGING TO THE TABLE.
THE INTENSIVE AND HIGH QUALITY ANNOTATION WE DO, I'M NOT SURE
IS NECESSARILY GOING TO BE ADOPTED BY INDUSTRY.
AND SO, THAT'S A GOOD STARTING POINT FOR US.
IT'S AN INTERESTING RESEARCH QUESTION FOR US ALSO.
>> THANK YOU VERY MUCH FOR YOUR TALK.
SO, MY QUESTION, THE ISSUES OF THE LONGEVITY OF THE DATA AND
ISSUES THAT MAY NOT BE ETHICAL BUT MORE MEDICAL, LEGAL IN
NATURE BUT I THINK THEY ARE RELATED.
THE FIRST QUESTION IS THE ISSUE OF ANNOTATION AND THE
EXPECTATIONS AS FAR AS HIGHWAY OFTEN THAT NEEDS TO BE DONE.
HOW LONG THAT NEEDS TO CONTINUE. AS WE LEARN MORE ABOUT ALL KINDS
OF DISEASES, THE BURDEN ON THE INVESTIGATORS TO CONTINUE TO
REANNOTATE FOR 20 YEARS AFTER WE HAVE THIS DATA ON A PERSON.
THE SECOND IS ABOUT THE DATA ITSELF AND RELATED ALSO IN THAT
WHAT HAPPENS WITH THE HIRES AND THIS INFORMATION IS THERE AND
WHAT ARE THE ACCESS ISSUE AND WE ARE NOT GIVING THEM THAT
INFORMATION ON A DISK. HOW DO THESE PATIENTS --
WHAT SORT OF ISSUES HAVE YOU DISCUSSED IN RELATION TO THIS
AMONG YOUR INSTITUTE? SO WHEN WE TALKED WITH OUR
PARTICIPANTS, WE SIGNED OUT TO HOPING THAT THEY CONTINUE TO
STAY IN CONTACT WITH US AT LEAST FOR THEIR MINOR CHILDREN UNTIL
THEIR CHILDREN ARE EASTERN BUT WE PUT THE BALL IN THE
PARTICIPANT'S COURT. THAT IS THAT WE WOULD LIKE TO
INITIATE CONTACT WITH US IN AN IDEAL WORLD WHEN THEIR CHILD IS
IN A POSITION TO MAKE THESE KINDS OF DECISIONS.
AND I THINK THIS ANOTHER THING THAT IS A NUANCE WITH
PARTICIPANTS, WE TALK ABOUT HOW WE PLAN TO DO SOME REANNOTATION
MAYBE IT WILL BE EVERY 6 MONTHS AND MAYBE IT WILL BE ONCE A YEAR
AND MAYBE EVERY TWO YEARS AND MAYBE WHEN MORE ACTABLE
TECHNIQUES COME OUT TO MAKE SENSE OF THE DATA AND I THINK
THAT IS PART OF THE REASON WHY WE ALERT THEM TO THE FACT THAT
THIS IS NOT HITTING ENTER ON A COMPUTER PROGRAM AND SOME SORT
OF OUTPUT. THAT WOULD MAKE THIS ALL
ATTRACTABLE BUT RIGHT NOW THERE ARE REALLY SERIOUS
CONSIDERATIONS AND WHEN WE THINK ABOUT THE INTERACTION BETWEEN
OUR TIME IN THE LABORATORY AND WHAT OUR GOAL IS, I THINK THAT
MOST PARTICIPANTS WOULD RATHER THAT WE DEVOTE MORE RESOURCES TO
TRY TO UNCOVER THE GENETIC CAUSE FOR THE DISORDER OF INTEREST
THAN IN REANNOTATING EXHAUSTIVELY THE SECONDARY
VARIANTS. I THINK IT'S A GREAT QUESTION.
>> THERE ARE DIFFERENT APPROACH THAT IS HAVE BEEN APPROVED.
WITH OTHER STUDIES WITH MORE FOCUSED OBJECTIVES, IT'S ARGUED
THAT THE OBLIGATION TO CONTINUE TO LOOK AT AND INTERROGATING AND
DISCLOSING INCIDENTAL FINDINGS GOES FOR THE DURATION OF THAT
PRIMARY STUDY AND NO FURTHER. SO IF A STUD LE TAKE THREE YEARS
TO GENERATE THE SOURCE OF RESULTS WE HAVE BEEN HEARING
ABOUT, AND THAT IS WHEN INVESTIGATORS WILL BE ACTIVELY
USING THE DATA, THAT IS HOW LONG WE WOULD EXPECT THE OBLIGATION.
AND IT'S PRACTICAL IN A CERTAIN WAY AND WE CAN'T EXPECT THAT
EVERY YEAR, EVERY FEW MONTHS OR EVERY FEW WEEKS, SOMEBODY WILL
BE ABLE TO LOOK BACK INTO THE LITERATURE AND UPDATE THEIR
KNOWLEDGE AND WHAT THEY ARE FINDING AND HOW THAT REALITIES
TO VIOLATES AND HAVE THE RESOURCES TO DISCLOSE IT.
THERE ARE SOME PRACTICAL LIMITS BUILT INTO STUDIES THAT LOOK
ROUGHLY LIKE THAT. >> --
SUBJECT POSITION ON RECEIVING RESULTS LEGAL OBLIGATION FOR
RESEARCHERS? IMAGINE A SITUATION WHERE HE
DEVELOPS A DISORDER LATER, IS THIS PERSON ABLE TO GO BACK TO
THE RESEARCHER AND QUESTION ABOUT THAT?
>> SO I'M NOT A LAWYER. AND I THINK THE LEGAL STATUS OF
A LOT OF QUESTIONS AROUND THIS AREA IS UNCERTAIN.
INC. SOME PEOPLE WORRIED THEY MAKE DECISIONS OUT OF FEAR OF
LITIGATION AND PRACTICE STANDARDS EMERGE BASED ON THEIR
DECISION BASED ON THAT FEAR OF LITIGATION AND THINGS EVOLVE IN
THAT WAY. I WOULD PREFER A CAREFUL
APPROACH DESIGNED IN SOUND AND I WOULD HOPE THAT CASE LAW AND
OTHER THINGS FLOW FROM THAT BUT I'M NOT AN EXPERT IN THESE
AREAS. MY COLLEAGUE IS TRAINED AS A
LAWYER AND HE IS, WITH SOME OF HIS LEGAL COLLEAGUES, WORKING
VERY HARD ON SOME OF THESE QUESTIONS SO I ALSO ENCOURAGE
YOU TO STAY TUNED. IT'S A GOOD POINT AND THAT'S
ABOUT THE BEST ANSWER OR AT LEAST THE BEST I CAN GIVE YOU ON
THAT. >> THANK YOU.
EXCELLENT PRESENTATIONS. AND I'M GOING TO ASK SARAH
ANOTHER ONE. SO ONE OF THE THINGS THAT JUMPED
OUT AT ME FROM YOUR EXAMPLE CASE YOU USE IS ONE OF THE
STIPULATIONS THAT THE PSEUDOIRB GAVE TO THE RESEARCHER WAS TO
IDENTIFY GENETIC COUNSELING SERVICES AND THIS IS AN
IMPORTANT THING FOR THE CLINICAL CENTER AND THE NIH TO BE
THINKING ABOUT AND TALKING ABOUT BECAUSE ALL THE GENETIC
COUNCILLORS I KNOW ARE VERY BUSY AND OVER WORKED AS IT IS WITH
THEIR OWN PROTOCOLS AND RESPONSIBILITIES AND THE GENETIC
CONSULT SERVICE, A VERY ACTIVE SERVICE, HAVE QUITE A PRESENCE
IN THE CLINICAL CENTER AND I PARTICIPATE, IT ISN'T STAFFED
SUFFICIENTLY TO BE ABLE TO OR ISN'T APPROPRIATE TO TALK ABOUT
OTHER PEOPLE'S SEQUENCING. I DON'T KNOW WHAT IT MEANS TO
FIND A GENETIC COUNSELOR TO FIND HELP.
I THINK THAT'S A MEANINGLESS RECOMMENDATION UNLESS WE HAVE
COME UP WITH SOME SORT OF SYSTEMATIC WAY WHERE THERE IS A
SERVICE OR A PERSON AVAILABLE TO THEM OR DESIGNED POSITION
STATEMENTS IN ORDER TO IMPLEMENT THIS.
>> I'M SO GLAD YOU CALLED ME ON THAT.
WE HAVE LEARNED THAT YOU'RE RIGHT.
-- WHICH VARIANTS OR TO REALLY
DICTATE HOW DISCHLORRIER WOULD OCCUR AND WE ARE AWARE WE HAVE
MEMBERS WHO ARE GENETIC COUNCILLORS.
AND WE WERE SCRAMBLING FOR IDEAS TO HELP A BENCH SCIENTIST WHO
HAD NEVER SUBMITTED A PROTOCOL TO THE IRB AND NEVER WORKED
DIRECTLY WITH GENETIC COUNCILLORS.
I HAVE SINCE LEARNED A COUPLE OF THINGS AND THE CONSULT SERVICE
ISN'T AVAILABLE ON DEMAND TO DO THIS WORK.
THEY ARE AVAILABLE FOR THE KINDS OF PROTOCOLS WHERE IT'S
RELATIVELY RARE THAT SOMETHING IS GOING TO COME UP.
THIS HAS BEEN A WILLINGNESS TO BE CALLED IN THE MUCH MORE
SPORADIC KINDS OF CASES LIKE THE ETHICS CONSULT SERVICE HAS BEEN
CALLED IN TO HELP WEIGH IN ON VERY DIFFICULT DECISIONS ABOUT
FINDINGS. ONE IDEA IS TO TO E PLOY A
GENETIC COUNSELOR IN THE PROTOCOL SERVICE CENTER WHO IS
AVAILABLE TO THE INSTITUTE AND THAT'S A GREAT IDEA OF THAT --
THAT REQUIRES FUNDING AND PART OF THE RATE LIMITING STEP THERE
IS FIGURING OUT HOW TO FUND ANOTHER POSITION.
SO THERE IS IDEAS LIKE THAT BUT IT'S ONE OF THE BOTTOM --
BOLTS NECK WE REALLY NEED TO BE AWARE OF AND THAT I URGE FUNDERS
OF RESEARCH AND INSTITUTE DIRECTORS AND CLINICAL DIRECTORS
TO BE THINKING OF BECAUSE THIS IS A VERY REAL NEED THAT IS NOT
CURRENTLY WIDELY AVAILABLE TO OUR INVESTIGATORS.
SO WE REALIZE THAT AND I THINK THAT MIGHT BE MOTIVATING IN PART
WHY THE IRB AND WHY PROTOCOLS HAVE PULLED BACK A LITTLE BIT
FROM SUCH A ROBUST REQUIREMENT FOR DISCLOSING THE FINDINGS
BECAUSE IN REALITY, WE ARE NOT SURE THAT PEOPLE HAVE THE
CAPACITY TO IDENTIFY THEM OR DISCLOSE THEM RESPONSIBLY.
>> BUT YOUR POINT AT THE END OF YOUR TALK IS YOU WANT THE
INVESTIGATORS TO BE THINKING THROUGH THE RAMIFICATIONS AND
WHAT RESOURCES WILL BE AVAILABLE.
>> RIGHT. >> MY LAST POINT IS NOT
ORIGINALLY MINE SO I'M PROBABLY VOICING THINGS OTHER PEOPLE HAVE
SAID TO ME BUT IT RESINATED WITH ME THIS AFTERNOON AROUND THE
SEMANTICS OF VARIANTS BECAUSE EVEN THOUGH JENNIFER'S TALK WAS
ENTITLED INCIDENTAL FINDINGS, SHE NEVER USED THAT PHRASE
THROUGHOUT HER TALK. AND JULIE USED VARIANTS THE
WHOLE TIME AND SARAH, I NOTICED YOU USE INCIDENTAL FINDINGS.
I BRING IT UP BECAUSE THAT'S THE VERBIAGE IN THE BIOETHICS
LITERATURE AND THERE IS SOME EXCELLENT WRITINGS RELATED TO IT
BUT I THINK JENNIFER AND JULIE EMBODY THE THE FACT THAT THESE
ARE NO LONGER INCIDENTAL FINDINGS.
WE NEED TO GET RID OF THAT LANGUAGE.
WE NOO -- INVESTIGATORS TO ACKNOWLEDGE
FROM THE BEGINNING THEY ARE GOING TO FIND VARIANTS AND HOW
THEY ARE GOING TO MANAGE THEM, EVEN INCIDENTAL OR SURPRISING.
IT'S ANTICIPATED AND IT NEEDS TO BE ANTICIPATED.
>> AS SUZANNE SAYS, WE NEED TO STOP UNANTICIPATING IT.
I TAKE THAT POINT AND I THINK I HAVE TO USE MORE --
I HINTED AT THAT THE I THINK THIS IS WHERE IT'S GOING BUT I'M
WILLING TO TAKE THAT SUGGESTION AND BE MORE MINDFUL OF THAT.
>> AS SOMEBODY WHO IS ON THE CONSULT SERVICES, WE ARE
STARTING TO GET PEOPLE WHO ARE ASKING IF WE CAN PROVIDE EXOMES
OR HOW THEY CAN GO ABOUT GETTING EXOMES DONE ON THEIR PATIENCE
AND IT MAKES SENSE IF YOU'RE LOOKING DOWN THE BARREL OF
FINE,000 OR 10,000 DOLLARS WORTH OF MOLECULAR TESTING YOU MIGHT
WONDER IF YOU COULD GET SOMETHING ESSEX --
LESS EXPENSIVE THAT MIGHT ANSWER QUESTIONS FOR YOU ON A CLINICAL
BASIS. AND NHGRI, WE HAVE TO HAVE A
DISCUSSION ABOUT WHETHER WE ARE GOING TO TAKE A LEADERSHIP ROLE
OR JUST WATCH THINGS AS THEY EVOLVE WITH REGARDS TO THE
TRANSITION OF EXOMES INTO THE CLINICAL REALM.
SO I THINK IT'S SOMETHING TO OBSERVE ON THE GROUND.
>> I HAVE A FEW MORE COMMENTS. FIRST YOU RAISE THE ISSUE OF
EXOMES AND TARGETING THINGS. I THINK THAT IS IRRELEVANT TO
THE TOPIC OF WHOLE EXOME SEQUENCING OR WHOLE GENOME
SEQUENCING. THAT IS THE TRADITIONAL WAY OF
TARGETING A SPECIFIC GENE OR A SPECIFIC SET OF GENES WITHIN AN
EXOME. THAT CAN BE DONE BUT THAT'S NOT
WHAT WE ARE TALKING ABOUT TODAY. THE SECOND POINT IS THAT I THINK
ALL OF US HERE TODAY ARE ON THE SIDE OF THE GODS WE ARE SAYING
ETHICS ARE MOVING IN CERTAIN DIRECTIONS AND WE SHOULD GIVE
ALL THE INFORMATION POSSIBLE TO THE PATIENTS.
THAT'S NOT WHAT IS HAPPENING RIGHT NOW.
THERE REALLY ARE STILL PROTOCOLS COMING AROUND AND BEING APPROVED
THAT SAY WE ARE GOING TO HIDE INFORMATION AND THAT'S THE WAY
IT IS. AND THE IRBs ARE AYOU WILLING
THAT TO PASS. SO I THINK THAT'S A REALLY NASTY
SITUATION THAT WE AREN'T DEALING WITH AT ALL.
AND WHAT WAS THE THIRD ISSUE. LET'S ANSWER THE FIRST TWO AND
THEN WE'LL GET TO THE THIRD. >> I'M NOT SURE THE FIRST POINT.
>> THAT YOU MENTIONED TARGETING AN EXOME AND I THINK THAT
REPRESENTS AN EXAMPLE OF THE TRADITIONAL THERAPY OF HAVING
BASICALLY A TARGETED GENE. >> SO I THINK THIS WAS A
SEMANTICS ERROR THERE WITH VERBIAGE.
I DON'T USE THE WORD, WHOLE, VERY MUCH BECAUSE --
WE TALKED ABOUT THE FACT THAT WHOLE IS SAY A LITTLE BIT
MISLEADING. IT'S REDUNDANT.
IF YOU'RE SAYING OHM IT'S ALL OF THEM AND IF YOU'RE SAYING WHOLE,
YOU COULD MISLEAD PEOPLE BECAUSE YOU ARE MISSING THINGS FOR
TECHINAL REASONS. I JUST ASSUME WHEN I SAY EXOME
WE ARE TALKING ABOUT ALL THE GENES OR AS MANY AS CAN BE
CAPTURED. WHAT WAS THE SECOND?
>> IN SEPTEMBER OF 2011, WE HAVE GROUPS THAT ARE SAYING THAT WE
ARE PLANNING TO GIVE ONLY SELECTED INFORMATION AND WE PLAN
TO HIDE THE REST THAT. IS HAPPENING ALTHOUGH MOST OF US
HERE FEEL IT IS UNETHICAL. >> SO I WANT TO CLARIFY THAT.
MY INTENTION WAS TO ACKNOWLEDGE THAT THERE ARE THOSE STUDIES
BEING APPROVED AND AT LEAST TRY TO CHARACTERIZE ARGUMENTS THAT
SUPPORT THOSE MODELS ETHICALLY UNDER CERTAIN CIRCUMSTANCES SO,
ALTHOUGH I THINK THERE IS EMERGING TRENDS, I THINK THEY
MIGHT VARY WITHIN THE INTRAMURAL RESEARCH PROGRAM WHERE WE HAVE
CERTAIN KINDS OF EXPERTISE AVAILABLE TO US MORE SO THAN IN
THE OUTSIDE WORLD. I THINK THERE ARE TRENDS
EMERGING BUT I DON'T THINK IT'S UNIVERSAL AND I DON'T THINK IT'S
UNIVERSALLY AGREED UPON AND I THINK THERE IS ROOM FOR MULTIPLE
ETHICALLY SUPPORTABLE APPROACHES IN THIS RESEARCH AREA.
I'M SURE THERE ARE AS MANY PEOPLE OUT THERE WHO WOULD
DISAGREE WITH SOMETHING I SAID ABOUT THE ETHICAL ARGUMENTS.
BUT I DIDN'T WANT TO SUGGEST THAT THERE IS AN AGREED UPON
CONSENSUS ABOUT ONE WAY THIS OUGHT TO BE DONE EVEN THOUGH WE
HEARD PRETTY STRONGLY PEOPLE ARE TRYING TO ENCOURAGE US IN GOING
IN THAT DIRECTION. I THINK THOSE WORLDS CAN COEXIST
IN AN ENVIRONMENT WHERE WE ARE DEVELOPING EMPIRICAL DATA AND
TRYING TO LEARN WHAT BEST PRACTICES ARE AND HOW TO SHOW
THEM AND COMMUNICATE THEM OUTWARD AND GENERATE RESOURCES
FOR THEM. >> SO MY THIRD POINT IS KIND OF
A SUMMATION WHAT HAVE YOU JUDGE JUST SAID AND WHAT WAS SAID OVER
HERE. THE ISSUE OF RESOURCES FOR
COUNSELING. HERE AT THE NIH, ALL OF YOU, THE
WHOLE TRAINING PROGRAM, WE ARE BLESSED WITH A LOT OF RESOURCES
OUTSIDE OF THE NIH. I THINK IT MUST BE A MINUSCULE
REPRESENTATION OF WHAT WE ARE DOING AND THE COUNSELING
SERVICES MUST BE OVER BURDENED TO UNBELIEVABLE EXTENT.
>> AGREED. >> CAN I GET BACK TO YOUR SECOND
POINT? IS THAT BETTER?
>> I THINK IT IS AGAIN IMPORTANT FOR US TO KEEP IN MIND THAT
PEOPLE ARE VOLUNTARILY WANTING TO PARTICIPATE IN RESEARCH AND
THIS HASN'T HAPPENED TO US BECAUSE I DO THINK THAT FOR OUR
EXOME PROTOCOLS, WE ARE SELECTING 4 PEOPLE WHO ARE
INTERESTED IN THIS KIND OF INFORMATION AND WHAT THEY COULD
LEARN. SO I DON'T THINK WE HAVE A WHOLE
LOT OF PEOPLE WHO SIGN UP AND HAVE OR WHO ARE EXPECTING TO
NEVER GET RESULTS. HOWEVER, I THINK THAT IT IS
POSSIBLE TO DESIGN A PROTOCOL WHERE THAT IS VERY CLEARLY
COMMUNICATED TO PARTICIPANTS. THIS IS REALLY MORE LIKE GIVING
BLOOD OR PARTICIPATING IN BIOBANKS OR TISSUE BANKS AND
THAT THAT COULD BE OKAY IF PARTICIPANTS REALLY HAVE A
THOROUGH UNDERSTANDING THAT THAT IS WHAT THEIR SAMPLE WILL BE
USED FOR AND THAT THERE WILL BE NO WAY FOR INVESTIGATORS TO
RETURN RESULTS TO THEM. SO I THINK THAT IS WHAT
YOU'RE -- >> YES.
>> SO I HAVEN'T THOUGHT ABOUT THESE ISSUES A WHOLE LOT IN THE
PAST BUT YOU KNOW, WE HAVE GENETIC DISORDERS I THINK
SIMILAR TO WHAT YOU'RE TALKING ABOUT WHERE A PATIENT IS COMING
IN, A CHILD WHO HAS A DISORDER AND THE FAMILY'S GOAL IS TO
DIAGNOSIS THAT DISORDER. AND THEY DON'T WANT TO FIND OUT
THAT MOM HAS A BRCA MUTATION AND JUST FROM THE SAMPLING OF
RESOURCES IT SEEMS TO ME IF YOU'RE GOING TO DO GWAS AT THREE
PEOPLE AND YOU'RE LUCKY ENOUGH TO GET A RESULT THAT MEANS IT
SOMETHING, THAT'S 3000 DOLLARS F NOW YOU FIND OUT THAT MOM HAS
BRCA AND YOU WANT TO TELL MOM HAS BRCA AND YOU NEED A TEST, MY
IMPRESSION IS THAT IS RELATIVELY EXPENSIVE.
AND YOU'RE TALKING ABOUT ADDING A LOT OF MONEY TO INFORM HER OF
THAT WHICH SHE MAY OR MAY NOT EVEN WANT TO KNOW TO BEGIN WITH.
SO I WOULD TAKE THE OPPOSITE FINDING WHICH IS, WE HAVE TO
CONSERVE RESOURCES AND WE HAVE TO COMMUNICATE CLEARLY WITH THE
PARTICIPANTS OUR GOALS AND I WOULDN'T CONSIDER IT HIDING
INFORMATION IF YOU FIND SOMETHING LIKE THAT AND DON'T
REPORT IT, IT'S -- NO HARM NO FOUL AS SARAH POINTED
OUT. MOM DEPENDENT KNOW THAT TO BEGIN
WITH. MOM DIDN'T COME TO THE NIH FOR
THAT PURPOSE AND HOW IS MOM HARMED BY NOT KNOWING?
>> BECAUSE SHE COULD DIE. SO AGAIN, THIS IS TOTALLY
ANECDOTES AND YOU PROBABLY HAVE A LOT TO ADD TO THIS TOO.
BUT WHEN WE WERE THINKING ABOUT DESIGNING THIS PROTOCOL TO
ELUCIDATE THE MOLECULAR ETIOLOGY, MY INITIAL THOUGHT WAS
PERHAPS THIS IS ALMOST COHERSIVE TO ASK PEOPLE TO PARTICIPATE AND
ALMOST AS COERCIVE ASPECT TO ASK THEM TO BEEN ALL OF THE OTHER
INFORMATION THAT THEY COULD LEARN BUT AS I TALKED TO
PARTICIPANTS, ALL OF THEM ARE TREMENDOUSLY GRATEFUL TO HAVE
THE OPPORTUNITY TO LEARN THAT INFORMATION AND IN THE CASE OF
ACTIONABLE VARIANCE, AGAIN, I THINK ON THE INDIVIDUAL LEVEL,
THESE ARE FAMILIES WHO HAVEIL CHILDREN.
THEY ARE YOUNG. THE PARENTS ARE IN 30s AND
40s RIGHT AT THE TIME WHEN SCREENING AND INTERVENTION COULD
MAKE A HUGE DIFFERENCE AND THEIR MAIN GOAL IS TO MAKE THE LIFE OF
THEIR CHILD AND BE AROUND TO TAKE CARE OF THEIR CHILD WHO MAY
NEED LIFELONG GOALS. I THINK IT'S THE OPPOSITE OF NO
HARM NO FOUL. WE HAVE THE --
WE CAN'T PRETEND THAT SUCH A VARIANT DOESN'T EXIST AND WE
HAVE A HUGE OBLIGATION TO PROVIDE THAT INFORMATION TO THE
FAMILY. UP AND IT'S CRITICAL HEALTH
INFORMATION THEY VIEW AS A HUGE POTENTIAL BENEFIT AND I THINK
THAT IS WHAT MANY OF THEM SAY WHEN THEY TALK ABOUT ANY OF
THEIR SECONDARY VARIANCES. TELL ME ANYTHING ABOUT MY HEALTH
BECAUSE I WANT TO BE AROUND FOR MY KID AND IF THERE IS ANYTHING
I CAN DO OR ANY IMPLEMENTATION I CAN PUT INTO PLACE, THAT IS
EXTREMELY DESIRABLE INFORMATION TO PARTICIPANTS.
[OFF MIC] >> SO I THINK YOUR QUESTION WAS
THAT THEN SOMEONE WILL SAY WE ARE GOING TO SEQUENCE THE MIN
NUMB NUMBER OF PEOPLE BECAUSE IF WE DON'T GET BACK TO
PARTICIPANTS AND THEY ARE ASSUMING THAT EVERYTHING IS
OKAY, AND WE DO TALK TO PEOPLE HOW THIS ISN'T AGAIN JUST
BECAUSE WE HAVEN'T TOLD THEM ABOUT SOMETHING, DOESN'T MEAN
THEIR RISK FOR THAT DOESN'T EXIST.
SO THAT IS A VERY REAL WAY TO ADDRESS THAT SPECIFIC.
>> I WOULD ALSO SAY, AS FAR AS COSTS, WE ARE, FOR WHERE WE
LOOKED AT 572 INDIVIDUALS, I THINK IF YOU WANT TO LOOK AT
THINGS LIKE BRCA1 AND 2 VARIANTS, AND HYPOTHERMIA AND
THINGS LIKE THAT, WE ARE PROBABLY GOING TO END UP WITH,
20, 30, VARIANTS THAT WE FEEL LIKE IF WE DON'T GIVE THESE BACK
TO THESE PATIENTS, THEY COULD DIE TOMORROW OR GET BREAST
CANCER TOMORROW OR WHATEVER. AND IT'S ONE-10 MAYBE.
I DON'T KNOW WHAT IT BREAKS DOWN TO BUT IT'S NOT LIKE YOU'RE
GOING DO HAVE 10 VARIANTS TO RETURN.
SO THE COST I DON'T THINK IT'S THAT MUCH.
IT'S NOT A WHOLE GENE SEQUENCING COST.
IT'S A SINGLE VARIANTS COST. IT COSTS ME VERY LITTLE TO
RETURN THAT TEST AND RETURN THAT RESULT TO SOMEONE.
EVEN IF I WAS GOING TO OUTSOURCE IT, IT'S PROBABLY A FEW HUNDRED
DOLLARS FOR ME TO GET A RESULT TO RETURN TO SOMEONE AND IF IT'S
300 DOLLARS FOR A SINGLE VARIANT, IN 1 OUT OF 10 STUDIES
OR WHATEVER, IT'S NOT THAT MUCH MONEY.
THE COST OF ANNOTATION YOU COULD ARGUE TODAY WITH THE TIME IT
TAKES IS EXPENSIVE BUT I REALLY THINK THE TOOLS WILL CONTINUE TO
GET BETTER AND WHILE TODAY IT TAKES HOURS TO DO A TRIO, I
DON'T EXPECT THAT TO CONTINUE, THAT COST TO CONTINUE.
THE COST OF VALIDATING WILL CONTINUE BUT FOR THESE THINGS
LIKE BRCA VARIANT, I DON'T KNOW WHAT IS THE VALUE OF SOMEONE'S
LIFE AND SOMEONE'S KNOWING THIS INFORMATION AND BEING ABLE TO
ACT ON IT? >> I WANTED TO ASK A QUESTION
ABOUT A SOMEWHAT DIFFERENT ETHICAL ISSUE THAT WAS MADE A
REFERENCE TO BUT WE HAVEN'T BEEN TALKING ABOUT --
ANOTHER ETHICAL QUESTION YOU BOTH MADE SOME REFERENCE TO BUT
WE HAVEN'T DONE TALKING ABOUT. THE POSSIBILITY, PROJECTICALITIY
OF CALLING THESE DATA CONFIDENTIAL.
AND I GUESS JULIE, YOU WERE THE ONE THAT SAID SOME PEOPLE ARE
EXITED ABOUT PARTICIPATING AND HAVING ACCESSES TO A NEW
TECHNOLOGY SOONER AND ENVISION A TIME WHERE IT WILL BE PART OF A
CLINICAL CARE. THE DIFFERENCE IS A CLINICIAN
WON'T BE ENTERING THE TEST RESULTS IN DB GAP AND I WONDER
IF YOU COULD TALK MORE ABOUT THAT AS AN ETHICAL ISSUE AND
SECONDARILY ABOUT THE POSSIBILITY THAT INFORMED
CONSENT COULD EVER BEEN -- I MEAN, AS YOU SAID, IT'S A
TORRENT AND WE ARE AT THE BEGINNING OF UNDERSTANDING
OURSELVES WHAT IT MEANS. BUT THESE RECORDS ARE GOING TO
PERSIST LONG AS WE DO UNDERSTAND MORE AND MORE.
DO YOU THINK PARTICIPANTS CAN UNDERSTAND HOW CONFIDENTIAL
THEIR DATA ARE? >> THIS IS A REALLY INTERESTING
AND COMPLICATED AND EVOLVING AREA, THE ISSUE OF
IDENTIFIABILITY AS IT RELATES TO GENOMIC DATA AND A CERTAIN SENSE
THAT SEPTEMBER WHEN YOU HAVE IDENTICAL TWINS, EACH GENOME
SEQUENCE REALLY IS IDENTIFIABLE TO A PERSON IF YOU HAVE THE
REFERENCE SAMPLE, YOU CAN FIGURE OUT --
AND SOME GENOTYPIC INFORMATION TO HELP YOU PINPOINT WHO IS IN A
POOL OF DATA. THAT CALLS FOR MORE
SOPHISTICATED SECURITY MEASURES MORE CONTROLLED ACCESS MEASURES
TO CONTROL, WHO HAS PERMISSION TO GET INTO THE COMPUTERS THAT
CAN ACCESS THOSE DATA. IT CALLS FOR PAYING ATTENTION TO
REGULATIONS THAT PROHIBIT PEOPLE FROM USING THOSE DATA FOR CALL
IT NEFARIOUS, INAPPROPRIATE GOALS.
AND IT REQUIRES TO BE TRANSPARENT AND THERE ARE SOME
RISKS HERE AND WE CAN'T GUARANTEE ABSOLUTE
CONFIDENTIALITY. THERE IS ALSO SOME INTERESTING
QUESTIONS THAT EVEN WHEN WE DO OUR BEST TO DEIDENTIFY DATA AND
IF WE FOLLOW HIPPA REGULATIONS, THERE IS SOME IN CONSISTENCY
ACROSS THE DIFFERENT KINDS OF SECURITIY REGULATIONS OUT IS
THERE. IF WE HARMONIZE THOSE AND DO A
PERFECT JOB, THERE ARE STILL ETHNIC AND RACIAL IDENTIFIERS
ATTACHED TO IT. EVEN IF WE CAN'T IDENTIFY TO A
INDIVIDUAL, REMIGHT IMPLICATION GROUPS THAT.
HAS A SEPARATE CELT OF IMPORTANT IMPLICATION THAT IS I AND MY
COLLEAGUES ARE INTERESTED IN. BUT PEOPLE ARE FOCUSING IN ON
INFORMATIONAL RISK AND REVISING THE REGULATORY FRAMEWORK THAT
APPLIES TO THESE KIND OF DATA TO ENSURE THAT NOBODY THINKS THAT
ANYTHING CAN BE COMPLETELY DEIDENTIFIED AND THEREFORE NOT
SUBJECT TO OVER SITES AND HUMAN SUBJECTS REGULATIONS.
THERE ARE PROPOSALS THAT ARE BEING DISCUSSED TO HELP TAKE
SOME OF THE GAPS IN OVERSITE THAT COME ABOUT FROM LOOSE
DEFINITIONS IN THIS AREA. THAT'S AN OVERVIEW OF SOME OF
THE CURRENT DISCUSSIONS AND THINKING GOING ON.
BUT MAYBE JULIE WANTS TO TALK MORE ABOUT THE SPECIFIC
CHALLENGES. >> I THINK THAT IS ONE --
SO PART OF THE REASON WHY WE TRY TO HAVE TWO CONVERSATIONS ABOUT
PEOPLE -- WITH PEOPLE ABOUT PARTICIPATING
IN OUR STUDY WHERE WE TALK TO THEM OVER THE PHONE AND THEN
SEND THEM SOMETHING IN THE MAIL. PEOPLE PICK UP PARTS OF THE
PROTOCOL OF MOST CONCERN TO THEM.
IF SOME ARE IT'S THE KIND OF INFORMATION THAT I THEY MAY
LEARN AND OTHERS IT IS THE FACT THAT WE REALLY TRY VERY HARD TO
GUARANTEE AND PROTECT DATA IN EVERY WE CAN.
WE HAVE A CERTIFICATE OF CONTI DENT ATE AND PROCEDURES IN PLACE
AND AT THE END OF THE DAY IT'S HARD TO MAKE AN IRONCLAD PROMISE
BECAUSE OF THE INHERENT NATURE OF GENOMIC INFORMATION.
AND AGAIN THIS IS VERY ANECDOTAL.
THAT INTERVAL IS 9 MONTHS AND DURING THIS 9 MONTHS THAT WAS
THE BIG QUESTION THEY WERE GRAPPLING WITH.
IT'S INFORMATION THEY WANTED TO HAVE GENERATED ON THEM.
AND I GUESS SOMETHING HAPPENED AND THEY FIGURED IT WAS A RISK
WORTH TAKING. I THINK PARTICIPANTS UNDERSTAND
IT. AND CAN GRAPPLE WITH IT AND SOME
PEOPLE ELECT TO NOT TAKE THAT RISK AT THE END OF THE DAY.
>> THIS IS A QUICK QUESTION. AND IT'S FOR YOU.
YES, AS WE ARE MOVING TOWARDS THE 1000 DOLLAR GENOME AND AS
YOU'RE NODDING YOUR HEAD THAT THE CERTIFICATION IS PRETTY
CHEAP, OUT THERE IN UTAH, GENETICS IS CHARGING 4000
DOLLARS FOR BRCA -- BRCA ONE AND BRCA TWO.
HOW CAN THEY DO THAT AND HOW CAN WE MEASURE THIS?
>> I ACTUALLY AMGOING TO SUGGEST THAT YOU MIGHT WANT TO RAISE
THAT QUESTION WITH THE OFFICE OF GENERAL COUNSEL INSTEAD OF US.
BECAUSE -- IS IT NOT ON?
I WOULD SUGGEST THAT YOU RAISE THAT WITH THE OFFICE OF GENERAL
COUNSEL THERE ARE THOUGHTS ABOUT HOW WE SHOULD BE BEHAVING WITH
RESPECT TO PATENTED GENES SO WE SHOULD GET AN OFFICIAL OPINION
ON HER OFFICE IN THAT REGARD. I'M GLAD YOU RAISED THAT BECAUSE
IT IS SOMETHING THAT PEOPLE DO HAVE CONCERNS ABOUT.
SO I THINK FROM THERE, I WILL THANK ALL OF THE SPEAKERS FROM
TODAY. IT WAS A REALLY GREAT EFFORT.
I HOPE YOU FOUND THESE TALKS TO BE USEFUL TO YOU IN THINKING
ABOUT HOW YOU'RE GOING TO GO FORWARD WITH YOUR PROJECTS IN
THE FUTURE AND ALL OF US ARE HAPPY TO CONSULT WITH AND TALK
WITH YOU FURTHER IF YOU HAVE QUESTIONS INDIVIDUALLY AS WELL
AS WE WILL BE SENDING OUT A FOLLOW-UP SURVEY.
WE WANT TO KNOW FROM YOU, OUR COLLEAGUES, HOW THIS WAS USEFUL,
WHAT COULD BE DONE BETTER, IF IT COULD BE DONE AGAIN IN THE
FUTURE. THE TECHNOLOGY CHANGES, THE IRB
LANDSCAPE WILL CHANGE. PROBABLY EVERY 15 OR 20 MINUTES.
AND SO I THINK THERE WILL BE ANING ON GO NEED.
YOU TELL US HOW WE CAN SERVE YOUR NEEDS AND WE WILL BE EAGER
AND HAPPY TO DO THAT FOR YOU. SO THANKS ALL OF YOU WHO ARE
HERE AND THANK YOU FOR OUR WEB VIEWERS AND AS WELL THE PEOPLE
WHO WATCH THE RECORDED VERSION OF THE PROCEEDINGS.
SO THANK YOU FOR COMING. [APPLAUSE]