>> GOOD AFTERNOON.

WELCOME TO THIS MEETING OF THE

NIH BIOSPECIMENS INTEREST GROUP.

GLAD TO SEE YOU HERE TODAY, AND

WE PROBABLY HAVE A HUNDRED OR

MORE FOLKS ON A LIVE VIDEOCAST

ALSO.

SO HELLO TO YOU ALL.

WE DECIDED TO DO A SESSION ON

THIS IMPORTANT TOPIC OF

PEDIATRIC CONSENT.

TODAY WE HAVE THREE SPEAKERS,

DAVE WENDLER, SARA HULL AND

CAROL WEIL ALL FROM THE NIH.

I'LL START BY INTRODUCING DAVE

WENDLER WHO IS GIVING THE FIRST

TALK.

DAVE IS HEAD OF THE UNIT ON

VULNERABLE POPULATIONS IN THE

DEPARTMENT OF BIOETHICS AT THE

NIH CLINICAL CENTER.

HE IS A PHILOSOPHER TRAINED IN

THE PHILOSOPHY OF SCIENCE.

HE HAS SERVED AS CONSULTANT TO

NUMEROUS ORGANIZATIONS INCLUDING

COUNCIL OF INTERNATIONAL

ORGANIZATIONS OF MEDICAL

SCIENCES, THE AMERICAN COLLEGE

OF CARDIOLOGY AND THE NATIONAL

INSTITUTE ON AGING.

AND HIS CURRENT WORK FOCUSES ON

THE ETHICS OF RESEARCH WITH

INDIVIDUALS WHO ARE UNABLE TO

GIVE INFORMED CONSENT.

IN THIS CASE PEDIATRICS.

HIS TALK TODAY IS TITLED RISKS

AND THE NEED FOR CONSENT

PERMISSION.

>> THANK YOU.

I'M ALREADY FAILING WHATEVER

TEST IS BEING GIVEN TO ME HERE.

ALL RIGHT, LET'S TRY THAT.

WE HAVE TO BE GENTLE.

AS WAS MENTIONED, I'M A

PHILOSOPHER WHICH TYPICALLY

MEANS, AND PEOPLE WHO HAVE BEEN

HEARING MY TALKS I'VE BEEN

GIVING, I'VE BEEN TRAVELING A

LOT OVER THE LAST COUPLE MONTHS,

HAVE FOUND OUT THAT PHILOSOPHERS

TYPICALLY, INSTEAD OF GIVING

ANSWERS, ASK QUESTIONS.

AUDIENCES OFTEN GET FRUSTRATED

BY THAT.

SO THE GOOD NEWS IS TODAY, I'M

ACTUALLY GIVE OF GOING TO GIVE

YOU ANSWERS ON A COUPLE OF THESE

QUESTIONS.

AND I'M HOPING AT LEAST A COME

OF THE PEOPLE WHO HAVE LISTENED

TO MY PREVIOUS TALKS ARE GOING

TO TUNE IN TO THIS.

EVERY ONCE IN A WHILE I'LL TAKE

A STAND ON SOMETHING.

I'LL TAKE A STAND AND BASICALLY

ARGUE ESSENTIALLY ALL OF THIS

RESEARCH IS MINIMAL RISK, EVEN

THOUGH MOST IRBs A LOT OF

PEOPLE DON'T THINK THAT'S THE

CASE AND ARE PROBABLY MISTAKEN.

I THINK THAT HAS SOME

IMPLICATIONS ON CONSENT FOR

PEDIATRICS, AND PARTICULARLY

WITH RESECRETARY TO

BIOSPECIMENS.

SO I'LL TALK ABOUT THAT

PRIMARILY AND THEN I'LL TALK A

LITTLE BIT ABOUT CONSENT AND

ASSENT AT THE END OF THE TALK.

SO AT LEAST WITH RESPECT TO

PERMISSION AND WITH RESPECT TO

RISKS, WE SHOULD DO RESEARCH

WITH CHILDREN ONLY WHEN A COUPLE

CONDITIONS ARE SATISFIED.

FIRST OBVIOUSLY THE RESEARCH

SHOULD POSE ACCEPTABLE RISKS.

I'VE ADDED HERE, IT SHOULD BE

OBVIOUS TO EVERYBODY THAT YOU

DON'T EVEN CONSIDER DOING

RESEARCH WITH CHILDREN UNLESS

THE RESEARCH IS IMPORTANT,

UNLESS THERE'S SOME GOOD REASON

TO DO THE RESEARCH IN THE FIRST

PLACE.

BUT I'M GOING TO TAKE THAT FOR

GRAND FOR NOW.

SO ASSUMING THAT THAT CONDITION

IS SATISFIED, THEN THE RESEARCH

POSE ACCEPTABLE RISKS.

IN MOST CASES TALK A LITTLE BIT

ABOUT EXCEPTIONS.

YOU SHOULD GET THE PERMISSION OF

AT LEAST ONE PARENT AND THE

ASSENT OF CHILDREN, AT LEAST

CHILDREN CAPABLE OF PROVIDING

IT.

WE'LL TALK ABOUT THAT A LITTLE

BIT.

ALTHOUGH THIS ISN'T PART OF THE

FEDERAL REGULATIONS I THINK IT'S

ALSO IMPORTANT THAT WE RESPECT

AT LEAST SUSTAINED DISSENT OF

ALL CHILDREN.

SO WE'LL TALK ABOUT THAT.

FIRST ACCEPTABLE RISKS.

SO PEOPLE IN THE LITERATURE

OFTEN CALL THIS COMPONENT, WHICH

JUST REFERS TO THE FACT THAT

MOST RESEARCH STUDIES INCLUDES A

NUMBER OF DIFFERENT

INTERVENTIONS.

YOU HAVE A DRUG ADMINISTRATION,

YOU HAVE A COUPLE OF BLOOD

DRAWS, YOU HAVE AN MRI.

SO MOST STUDIES ARE BUILT UP OF

A NUMBER OF COMPONENTS.

THE IDEA HERE IS YOU SHOULDN'T

JUST EVALUATE THE OVERALL RISK

BENEFIT PROFILE OF A STUDY.

INSTEAD YOU SHOULD FIRST

EVALUATE THE RISK BENEFIT

PROFILE OF THE INDIVIDUAL

INTERVENTIONS THAT ARE PART OF

THE STUDY, AND THEN AFTER YOU'VE

DONE THAT, EVALUATE THE RISK

BENEFITS OF THE STUDY AS A

WHOLE.

SO GO THROUGH THAT.

SO SOMETIMES RESEARCH INCLUDES

STANDARD CLINICAL INTERVENTION.

SO FOR INSTANCE, A RANDOMIZED

ADD-ON TRIAL MIGHT GIVE SUBJECTS

IN BOTH ARMS THE STANDARD

EXISTING TREATMENT FO FOR THEIR

CONDITION AND THEN GIVE HALF THE

SUBJECTS SOME EXPERIMENTAL

ADD-ONS.

SO IN THAT KIND OF CASE FOR THE

MOST PART WE DON'T HAVE TO WORRY

ABOUT THE RISKS AND BENEFITS OF

THE STANDARD CLINICAL

INTERVENTION.

THE ASSUMPTION IS IF IT'S A

STANDARD CLINICALLY INDICATED

INTERVENTION, THEN IT'S IN

SUBJECT'S INTEREST TO GET IT AND

THEREFORE WITH A AR WE DON'T HAVE TO WORRY

ABOUT THE RISKS IT MIGHT POSE TO

SUBJECTS.

THERE'S ONE CAVEAT HERE WHICH IS

PRESUMABLY NOT GOING TO BE

TERRIBLY RELEVANT WITH RESPECT

TO RESEARCH AND BIOSPECIMENS

WHICH IS THE FACT THAT AT LEAST

IN SOME CASES A RESEARCH

INTERVENTION MIGHT INFLUENCE AND

IN FACT INCREASE THE RISKS OF A

STANDARD CLINICAL INTERVENTION.

SO IT'S IMPORTANT TO KEEP THAT

IN MIND AT LEAST IN SOME CASES.

SO LEAVING ASIDE THE

INTERVENTIONS, JUST FOCUS ON

RESEARCH INTERVENTIONS.

SO WHAT I THINK ABOUT THIS IS

FOUR STEPS TO EVALUATING THE

RISKS OF RESEARCH INTERVENTIONS

TO MAKE SURE THAT THEY'RE

ACCEPTABLE.

FIRST AS I MENTIONED, EACH

INTERVENTION IN A STUDY SHOULD

BE THERE FOR A GOOD REASON.

TYPICALLY BECAUSE IT'S GOING TO

BE NEEDED TO COLLECT INFORMATION

THAT IS VALUABLE AND THAT YOU

WOULDN'T BE ABLE TO GET

OTHERWISE PARTICULARLY BY LESS

RISKY MEANS.

SECOND, TO ALWAYS MINIMIZE THE

RISKS OF RESEARCH AND INDIVIDUAL

INTERVENTIONS WHEN YOU CAN.

WITH KIDS THIS MEANS TRYING TO

DO MOST KIDS AND AT LEAST SOME

OF OTHER ADULTS HATE NEEDLE

STICKS SO MINIMIZING NEEDLE

STICKS IS A GOOD IDEA, GETTING

RESEARCH BLOOD DURING CLINICALLY

INDICATED PROCEDURES IS A IDEA.

GETTING DATA FROM SCANS THAT'S

ALREADY BEEN DONE.

NOT TO REPEAT THEM.

IT'S A GOOD IDEA TO USE-CREAM AS

GOOD IDEA.

I WON'T SPEND TOO MUCH TIME ON

EITHER OF THOSE STEPS.

THE TWO STEPS I'LL FOCUS ON ARE

THREE MOSTLY AND A LITTLE BIT ON

FOUR.

ONCE YOU MINIMIZE THE RISK THEN

THE QUESTION IS WHETHER OR NOT

THE RISKS THAT WERE MADE ARE

ACCEPTABLE.

YOU DO THAT FOR EACH OF THE

INTERVENTIONS, ASK AND ANSWER

THAT QUESTION AND THEN YOU

COMPILE ALL OF THE, WHAT I CALL

NET RISKS THAT ARE POSED TO

SUBJECTS FROM THE INDIVIDUAL

INTERVENTIONS AND ASK WHETHER OR

NOT THAT CUMULATIVE TOTAL OF

RISKS IS ALSO ACCEPTABLE.

SO THAT'S ROUGHLY THE FRAMEWORK

THAT I'M GOING TO GO THROUGH.

SO SOMETIMES BEING IN RESEARCH

OFFERS A PROSPECT OF DIRECT AS

IT'S TERMED IN THE PEDIATRICIAN

REGULATION OR CLINICAL BENEFIT

IS ANOTHER WAY TO THINK ABOUT

IT.

TYPICALLY TWO SUBJECTS INCLUDING

CHILDREN.

SO SOMETIMES GETTING ACCESS TO A

PARTICULAR EXPERIMENTAL

INTERVENTION CAN BE IN THE

SUBJECT'S INTEREST.

WHETHER OR NOT THE RISKS OF

THESE INTERVENTIONS ARE

ACCEPTABLE, TYPICALLY CAN JUST

BE DETERMINED BY DETERMINING

WHETHER OR NOT POTENTIAL

BENEFITS OF GETTING THAT

INTERVENTION JUSTIFIES THE RISKS

THAT IT POSTS T POSE TO SUBJECTS.

IF IT DOES YOU'VE GOT AN

INTERVENTION AT LEAST WITH

REGARD TO RISK IS ACCEPTABLE.

THAT LEAVES THE QUESTION WHAT

ABOUT INTERVENTIONS THAT EITHER

DON'T OFFER ANY PROSPECT OF

DIRECT BENEFIT.

THAT'S THE STANDARD CASE OR

THERE'S ALSO FOR ANYBODY WHO

WANTS TO BE PHILOSOPHICAL BIT,

THERE ARE ALSO ODD CASES WHERE

THERE ARE INTERVENTIONS THAT

OFFER SOME POTENTIAL FOR BENEFIT

BUT THE POTENTIAL FOR BENEFIT

ISN'T SUFFICIENT TO JUSTIFY THE

RISKS, AND THOSE INTERVENTIONS

POSE WHAT I CALL NET RISKS.

SO FOR THOSE INTERVENTIONS, WE

NEED TO SIGNIFY OUT AND EVALUATE

THE RISKS -- FIGURE OUT AND

EVALUATE THE RISKS OR THE NET

RISKS OF THOSE INTERVENTIONS.

AGAIN WE NEED TO MAKE SURE THAT

BOTH THE RISKS OF THE INDIVIDUAL

INTERVENTIONS ARE ACCEPTABLE AND

ALSO THE ACCUMULATIVE RISKS, THE

RISKS OF ALL OF THE NET RISK

INTERVENTIONS INCLUDED IN THE

STUDY ARE ACCEPTABLE.

BUT THAT TOTAL IS ALSO

ACCEPTABLE.

SO TYPICALLY THIS IS CERTAINLY

TRUE WHEN WE TALK ABOUT

PEDIATRIC RESEARCH.

KNELT RISKS ARNET RISKS ARE CONSIDERED

ACCEPTABLE ONLY WHEN THEY ARE

SUFFICIENTLY LOW.

A LOT OF REGULATIONS AROUND THE

WORLD FOLLOW THE U.S.

REGULATIONS AND MAKE THIS

DETERMINATION.

SO WHAT COUNTS AS WHETHER OR NOT

A RISK IS SUFFICIENTLY LOW.

IT'S ACTUALLY AN INTERESTING

QUESTION IF YOU TRY TO ADDRESS

IT.

HOW WOULD YOU FIGURE OUT WHETHER

OR NOT RISKS ARE SUFFICIENTLY

LOW.

WHEN I GO TO DINNER PARTIES AND

PEOPLE ASK ME WHAT I DO AND THEY

TRY TO UNDERSTAND ONE OF THE

THING I ASK THEM ABOUT IS WHAT

THEY THINK ABOUT EXPOSING

CHILDREN TO RESEARCH RISKS FOR

THE BENEFIT OF OTHERS.

THE VAST MAJORITY OF PEOPLE, AT

LEAST THE PEOPLE I END UP HAVING

DINNER WITH SAY THAT'S OKAY AS

LONG AS THE RISKS ARE LOW

ENOUGH.

THE OBVIOUS EXPRESSION IS HOW DO

YOU FIGURE OUT WHAT CONSTITUTES

A SUFFICIENTLY LOW RISK IN THIS

REGARD.

IF YOU THINK ABOUT IT, I THINK

IT'S ACTUALLY A PRETTY HARD

CHALLENGE TO TRY TO RESOLVE.

I THINK THIS IS ONE OF THE

PLACES WHERE U.S. REGULATIONS

HAVE DONE I THINK A PRETTY GOOD

JOB.

SO BASICALLY WHAT U.S.

REGULATIONS DO TO ANSWER THAT

QUESTION IS THEY ASK US TO MAKE

A COMPARISON.

MAKE A COMPARISON BETWEEN THE

RISKS OF THE RESEARCH AND THE

RISKS THAT CHILDREN IN THIS CASE

FACE IN ORDINARY DAILY LIFE.

AND THE ROUGH IDEA IS THAT IF

THE RISKS OF THE RESEARCH DON'T

EXCEED, IF THEY'RE NOT GREATER

THAN THE RISKS THAT CHILDREN

FACE IN DAILY LIFE, THEN THERE'S

A PRESUMPTION THAT THOSE RISKS

ARE ACCEPTABLE EVEN IN THE

RESEARCH SETTING.

SO THE VALUE OF THIS IS BY

GIVING US THIS COMPARISON THAT

ESSENTIALLY GIVE US A BASELINE

AGAINST WHICH TO EVALUATE THE

ACCEPTABILITY OF RESEARCH SIXES.

SO THE QUIZ TODAY FOR EVERYBODY

IS ALLERGY SKIN TESTING.

I'M PROPOSING TO YOU, I WANT TO

DO A TEST, ALLERGY SKIN TESTING,

IT'S GOING TO BE A REALLY

INTERESTING FABULOUS STUDY,

GOING TO GET THE NOBEL PRIZE FOR

IT BUT TO DO IT I'VE GOT TO DO

OUR SKIN TESTING IN A BUNCH OF

HEALTHY 11 YEAR OLDS.

SO FOR THE MOST PART, ACCORDING

TO THE U.S. REGULATIONS, I CAN

ONLY DO THIS STUDY AND GET MY

NOBEL PRIZE IF THOSE RISKS ARE

MINIMAL.

WHAT DO PEOPLE THINK, ARE YOU

GOING TO PROVE MY STUDY.

ALLERGY SKIN TESTING HEALTHY 11

YEAR OLDS.

CAN I GO BACK, THAT'S THE

DEFINITION.

SO THE QUESTION IS WHETHER OR

NOT ACCORDING TO THAT

DEFINITION, ALLERGY SKIN TESTING

HEALTHY 11 YEAR OLDS QUALIFY AS

MINIMAL OR NOT.

ALL RIGHT.

MINIMAL RISK.

THREE, FOUR, FIVE, SIX.

THE NEXT CATEGORY IS CALLED A

MINOR INCREASE RISK.

MAYBE A LITTLE MORE, MAYBE NINE.

ANYBODY THINK IT'S MORE THAN A

MINOR MINIMAL RISK.

CLEARLY MORE THAN THE RISK OF

DAILY LIFE.

SO TWO LESSONS FROM THAT QUIZ.

FIRST IS NO MATTER WHAT YOU

GUESSED, YOU HAVE GOOD COMPANY

AT LEAST AMONG IRB CHAIRS AROUND

THE U.S.

SO THIS IS A SURVEY WE DID ABOUT

EIGHT YEARS AGO ONE OF THE

FELLOWS WHO IS NOW A MEMBER IN

OUR FACULTY.

IF YOU SEE THE HIGHLIGHTED ONE A

QUARTER OF THE IRB CHAIRS

THOUGHT IT WAS MINIMAL RISK,

ABOUT HALF, AND A QUARTER

THOUGHT IT WAS MORE THAN.

YOU'RE IN GOOD COMPANY, THAT'S

THE GOOD NEWS.

THE BAD NEWS IS THAT THIS MUCH

DISAGREEMENT AND THIS MUCH

DISPARITY IN JUDGING RISKS OF

RESEARCH PROCEDURES IS A REAL

PROBLEM.

ONE, IT'S A PROBLEM BECAUSE

THERE'S A WORRY ABOUT WHETHER OR

NOT WE'RE GETTING IT RIGHT.

ARE WE OVERPROTECTING KIDS OR

UNDER PROTECTING CHILDREN.

THE PEDIATRIC RESEARCH FOR RARE

CONDITIONS, YOU OFTEN NEED TO DO

STUDIES IN LOTS OF CENTERS.

SO PEDIATRIC STUDIES WILL BE 50,

100, 150 CENTERS.

IF YOU GOT THAT MANY IRBs

REVIEWING YOUR RESEARCH AND YOU

GET THIS KIND OF SPREAD ON THE

JUDGMENT OF RISKS, YOU'RE GOING

TO HAVE A LOT OF TROUBLE

FINISHING YOUR STUDY.

SO WHAT I'VE BEEN WORKING ON

OVER THE LAST FIVE YEARS IS TO

TRY TO FIGURE OUT WAYS TO GET US

TO BE MORE SYSTEMATIC ABOUT OUR

RISK EVALUATIONS AND THEN

HOPEFULLY AS A RESULT END UP

WITH MORE ACCURACY.

SO THE OTHER LESSON OF THIS IS

THAT IN A WAY THIS IS SORT OF A

SET UP.

I THINK PART OF THE PROBLEM IS

EXACTLY WHAT HAS HAPPENED IN

THIS ROOM.

THIS ROOM I JUST ASKED YOU SO

IT'S NOT LIKE I'M FORCING YOU.

WHEN YOU LOOK AT WHAT IRBs AND

INVESTIGATORS DO, FOR THE MOST

PART THEY DO ESSENTIALLY THE

SAME THING.

YOU ASK THEM HOW MANY ALLERGY

SKINS MINIMAL RISK OR NOT,

NOT,MR I,

MINIMAL RISK OR NOT.

THEY SCRATCH THEIR HEAD AND GIVE

YOU AN ANSWER.

WHERE DOES THAT ANSWER COME

FROM, PARTICULARLY BECAUSE MOST

OF US DON'T HAVE A LOT OF

EXPERIENCE WITH ALLERGY SKIN

TESTING IN HEALTHY 11 YEAR OLDS.

MOST OF US HAVEN'T DONE MRIs

IN HEALTHY 11 YEAR OLDS.

OR IF WE DO WE DON'T REMEMBER

WHAT THE EXPERIENCE IS LIKE.

THE PROBLEM IS THEY'RE MAKING

THESE JUDGMENTS WITHOUT DOING AN

A SYSTEMATIC WAY OR HAVING DATA.

I THINK THAT'S A LOT OF THE

PROBLEM.

I THINK THE ANSWER IS WE HAVE TO

GET MORE SYSTEMATIC ABOUT IT AND

NOT JUST RELY ON OUR INTUITIVE

JUDGMENTS.

PART OF THE PROBLEM IS WE'VE

BEEN EVOLUTIONARY CODED TO BE

VERY QUICK JUDGES OF RISKS.

SO THE REASON WHY WE'RE ALL HERE

IS BECAUSE OUR ANCESTORS WERE

VERY QUICK JUDGES OF RISK AND AT

LEAST IN MOST CASES PRESUMABLY

FAIRLY ACCURATE.

BUT THAT QUICKNESS SOMETIMES

LEADS US ASTRAY PARTICULARLY

WHEN IT'S WITH RESPECT TO

PROCEDURES WE DON'T HAVE

EXPERIENCE IN OUR DAILY LIVES

LIKE ALLERGY SKIN TESTING.

WE NEED TO BE MORE SYSTEMATIC

ABOUT IT.

HOW DO WE DO IT.

I THINK THERE ARE ROUGHLY FOUR

DIFFERENT WAYS YOU CAN IMPLEMENT

THE MINIMAL RISK STANDARD.

FORTUNATELY FOR TODAY I THINK

ONLY ONE OF THEM IS PRIMARILY

RELEVANT TO BIOSPECIMEN RESEARCH

SO I'M JUST GOING TO FORCE YOU

TO GO THROUGH THAT ONE.

YOU WON'T HAVE TO GO THROUGH ALL

FOUR OF THEM.

SO THIS ONE STARTS BY REMINDING

US AS OF THE DEFINITION.

SO THE POINT HERE IS THAT

MINIMAL RISKS ARE DEFINED IN

COMPARISON TO THE RISKS OF DAILY

ACTIVITIES OR ROUTINE

PROCEDURES.

AND THE CONSEQUENCE OF THAT IS

ANY ROUTINE PROCEDURE THAT

YOU'RE DOING IN YOUR RESEARCH BY

DEFINITION COUNTS AS A MINIMAL

RISK PROCEDURE.

SO THE OBVIOUS EXAMPLE, AND THIS

AT LEAST MOST PEOPLE FORTUNATELY

EVEN IN OUR SURVEY AGREED ON, IS

THAT A SINGLE BLOOD DRAW BECAUSE

IT'S A ROUTINE PROCEDURE, EVEN A

PEDIATRIC MEDICAL CARE, COUNTS

AS BY DEFINITION A MINIMAL RISK

PROCEDURE.

SO GIVES US A BASELINE.

ANYTHING THAT IS A SINGLE BLOOD

DRAW IS MINIMAL RISK.

ANYTHING THAT HAS RISKS NO

GREATER THAN A SINGLE BLOOD DRAW

ALSO COUNTS AS A MINIMAL RISK.

THERE'S THIS SORT OF LINE OF

REASON SOMETIMES LEADS OWN

REALLY SMART PEOPLE TO GET

CONFUSED.

WHAT WE JUST SAID IS IF A

PROCEDURE IS USED IN DAILY LIFE

OR ROUTINE EXAMINATION IT COUNTS

AS MINIMAL RISK.

SOME PEOPLE TAKE THE CONVERSE OF

THAT AND THINK IT'S ALSO TRUE

THAT IF A PROCEDURE ISN'T PART

OF DAILY LIFE OR ISN'T A ROUTINE

PROCEDURE, THEN IT'S NECESSARILY

MORE THAN MINIMAL RISK.

AND THAT ISN'T RIGHT.

AND THE EXAMPLE I LIKE TO USE

FOR THIS IS REIKI, I DON'T KNOW

IF PEOPLE KNOW WHAT THIS IS BUT

IT'S CALLED SORT OF A HANDS-ON

THERAPY.

I USED TO GO ON ROUNDS AT THE IC

A COUPLE YEARS AGO AND A COUPLE

OF PEOPLE THERE WERE DOING A

STUDY OF REIKI WHICH BASICALLY

TAKE PEOPLE WHO ARE VERY SICK

AND THE PRACTITION YOU ARE TAKES

THEIR HAND AND MOVES IT A COUPLE

INCHES ABOVE THE SICK PERSON'S

BODY SURFACE.

THE IDEA IS ROUGHLY AS I

UNDERSTAND IT THAT THE GOOD

ENERGY FROM THE PRACTITIONER IS

SUPPOSED TO INFUSE INTO THE SICK

PERSON.

THE BAD ENERGY FROM THE SICK

PERSON IS SUPPOSED TO BE SUCKED

OUT AND HOPEFULLY NOT INFECTING

THE PRACTITIONER.

THAT'S NOT SOMETHING THAT MOST

OF US UNDERGO IN DAILY LIFE BUT

I TAKE ANYTHING AS A MINIMAL

RISK PROCEDURE IN THE RESEARCH

SETTING, THAT'S GOT TO BE

MINIMAL RISK.

SO THAT'S JUST AGAIN TO

UNDERSCORE THE POINT THAT THE

FACT THAT IT'S NOT SOMETHING WE

UNDERGO IN OUR LIFE DOESN'T MEAN

IT'S NECESSARILY MINIMAL RISK.

IT DEPENDS.

WHAT DOES IT DEPEND ON.

IT DEPENDS ON WHETHER OR NOT

CHILDREN UNDERGO IT.

THE POINT OF THE REGULATION

ISN'T TO KEEP CHILDREN FROM

HAVING NEW EXPERIENCES.

THE POINT OF THE REGULATION IS

TO KEEP THEM FROM BEING EXPOSED

TO EXCESSIVE RISKS.

SO WHAT WE HAVE TO FOCUS ON IS

THE RISK LEVEL.

THE LEVEL OF RISKS POSED BY

SOMETHING LIKE REIKI.

THAT'S WHY REIKI MINIMAL RISK

NOT BECAUSE WE SEE IT EVERY DAY

OR EXPOSE TO A LOT BUT BECAUSE

THE LEVEL OF RISKS THAT IT POSES

IS PRESUMABLY REALLY REALLY LOW.

WHAT WE HAVE TO DO AGAIN IS LOOK

AT THE LEVEL OF RISKS.

ONE OF THE QUESTIONS PEOPLE ASK

IN THIS CASE.

IF WE'RE GOING TO USE THE

MINIMAL RISK STANDARD, RISKS OF

DAILY LIFE, WHOSE DAILY LIFE DO

WE TALK ABOUT.

SOME PEOPLE HAVE ENDORSED WHAT'S

CALLED A SUBJECTIVE

INTERPRETATION.

WHICH ROUGHLY MEANS THE RISKS OF

DAILY LIFE OF THE CHILDREN WHO

ARE GOING TO BE IN YOUR

RESEARCH.

NOW THERE'S A PROBLEM WITH THAT

INTERPRETATION WHICH IS ROUGHLY

THAT IT SEEMS TO IMPLY THAT

CHILDREN WHO HAVE WORSE OR

RISKIER LIVES CAN BE EXPOSED TO

GREATER RESEARCH RISKS EVEN IN

THE CONTEXT OF THE STUDIES THAT

DON'T OFFER THEM THE PROCESS

SPECT OF DIRECT BENEFIT.

THAT SEEMS TO MOST PEOPLE

INAPPROPRIATE.

ROUGHLY I THINK THAT SEEMS LIKE

A CASE OF EXPLOITING PEOPLE'S

BAD CIRCUMSTANCES TO MAKE THEM

WORSE OFF.

SO IT'S NOT MOST PEOPLE THINK

THE RISKS OF THE CHILDREN THAT

YOU'RE ACTUALLY GOING TO ENROLL

IN THE STUDIED BUT INSTEAD SO

THIS IS ACCORDING TO AN ILM

REPORT.

THE WAY THEY PUT IT, I THINK

THIS IS ROUGHLY RIGHT ALTHOUGH

MAYBE IT'S TOO COMPLICATED.

IT'S ROUGHLY THE RISKS IN THE

DAILY LIVES OF AVERAGE HEALTHY

NORMAL CHILDREN.

SO THE IDEA THEN IS WE FIND OUT

WHAT THE RISKS ARE IN THE LIVES

OF AVERAGE HEALTHY NORMAL

CHILDREN AND COMPARE THE LEVEL

OF RISKS POSED BY OUR RESEARCH

PROCEDURES TO THAT LEVEL OF

RISK.

IS IT HIGHER OR LOWER THAN THAT

LEVEL.

THAT'S THE QUESTION THAT THE

MINUTE MUST BE RISK STANDARD

ASKS US TO TRY TO ANSWER.

SO ONE OF THE THINGS, AS I SAID,

THAT'S REALLY VALUABLE ABOUT THE

MINIMAL RISK STANDARD IS IT

GIVES US A BASELINE, IT GIVES US

A COMPARATIVE FOR RESEARCH

RISKS.

THE PROBLEM IS I THINK IT NEEDS

INTO THIS TENDENCY I MENTIONED A

MINUTE AGO WHICH IS THAT WE ALL

TEND TO BE VERY QUICK JUDGES OF

RISK.

SO PARTICULARLY WHEN I TELL YOU

THE STANDARD WORKS BY AVERAGE

ORDINARY RISKS, IT'S THE RISKS

OF THE LIVES OF AVERAGE ORDINARY

KIDS THAT WE THINK I KNOW WHAT

THEY ARE.

I KNOW WHAT THOSE RISKS ARE.

WE THINK THAT WE DON'T NEED ANY

DATA, THAT WE ALREADY CAN

UNDERSTAND HOW TO INTERPRET

THOSE.

I DON'T KNOW IF PEOPLE KNOW THIS

DATA BUT THERE'S A LOT OF VERY

INTERESTING DATA IN PSYCHOLOGY

AND SOCIAL PSYCHOLOGY WHICH

SUGGESTS THAT ALTHOUGH WE'RE

OFTEN VERY GOOD JUDGES OF RISK,

WE JUDGE RISKS BASED ON CERTAIN

FUTURE STATISTICS WHICH

TYPICALLY TEND TO GET US IN THE

RIGHT DIRECTION.

BUT IN CERTAIN CASES

PARTICULARLY WITH UNFAMILIAR

PROCEDURES GET IT WRONG.

SO SOME ARE WE TEND TO JUDGE

THINGS WE'RE FAMILIAR WITH IS

LESS RISKY THAN THINGS WE'RE

UNFAMILIAR WITH.

ANYBODY WHO HAD NEXT PERIENCE, I

HAT ON IRBs ABOUT 15 YEARS.

WHENEVER YOU PRESENT A -- OR

LUMBAR PUNCTURE TO AN IRB, THE

PSYCHOLOGIST ON THE BOARD WILL

SAY THAT'S REALLY RISKY STICKING

A NEEDLE INTO SOMEBODY'S BACK.

THE ANESTHESIOLOGIST WILL SAY

THAT'S ABSOLUTELY NOTHING, I DO

THAT EVERY DAY.

SO IT'S NOT THAT THEY HAVE

DIFFERENT RISK LEVELS IS THEY

HAVE DIFFERENT LEVELS OF

FAMILIARITY WITH THE PROCEDURE.

SO WE CAN'T GO JUST WITH THAT.

WHAT WE NEED TO KNOW IS WE NEED

TO REALLY KNOW WHAT THE ACTUAL

RISKS ARE OF THE PROCEDURE.

SO WE NEED DATA ON THE RISKY

PROCEDURES AND WE NEED A METHOD

FOR IMPLEMENTING THAT DATA IN A

SYSTEMATIC WAY IF WE'RE GOING TO

DO BETTER THAN THE DATA

SUGGESTED IN THE STUDIED.

SO I MENTIONED THERE ARE FOUR

METHODS I THINK.

I'M JUST GOING TO BORE YOU WITH

ONE OF THEM TODAY WHICH I CALL

THE DIRECT COMPARISON APPROACH.

SO THIS I THINK IN SOME WAYS IS

ONE OF THE EASIEST APPROACHES

WHICH ROUGHLY SAYS THAT IN SOME

CASES THE RISKS OF RESEARCH

PROCEDURES ARE JUST LIKE THE

RISKS THAT CHILDREN FACE FROM

ROUTINE PROCEDURES OR AVERAGE

ORDINARY ACTIVITIES IN DAILY

LIFE.

WHEN THAT'S TRUE, YOU CAN JUST

COMPARE THEM, JUST SEE IF THE

RISKS ARE THE SAME ARE THE

LIKELIHOODS GREATER OR LESS AND

THAT GIVES YOU AWAY TO

SYSTEMATICALLY IMPLEMENT THE

MINIMAL RISK STANDARDS.

THERE'S JUST ONE EXAMPLE.

SO WE HAVE SOME DATA ON A NUMBER

OF DIFFERENT ACTIVITIES.

ONE OF THEM ORDINARY ACTIVITY IS

RIDING IN A CAR WHICH MOST KIDS

DO.

SO YOU CAN GET DATA ON THE

CHANCES THAT CHILDREN WILL DIE

FROM RIDING IN A CAR.

NOW IF I HAVE A STUDY WITH A

MAIN RISK WITH A RISK OF DEATH,

ONE WAY TO DETERMINE WHETHER

THAT STUDY POSES MINIMAL RISK OR

GREATER THAN MINIMAL RISK IS TO

EXAIRCOMPARE THE LIKELIHOOD OF DEATH

FROM A RESEARCH OR LIKELIHOOD OF

DEATH FROM AN ORDINARY CARE RIDE

AND THAT GIVES YOU A WAY WHETHER

OR NOT THAT INTERVENTION POSES

GREATER RISK OR MINIMAL RISK.

SOMETIMES MAYBE NOT ALWAYS THAT

IMPORTANT FOR BIOSPECIMENS

RESEARCH BUT NOTICE HERE ONE

POINT OF THIS IS THAT THE FACT

THAT SOMETHING POSES SOME CHANCE

OF A REALLY BAD OUTCOME DOESN'T

IMPLY THAT IT'S GREATER THAN

MINIMAL RISK.

MINIMAL RISK PROCEDURES CAN POSE

SOME RISK OF SERIOUS HARM, AS

LONG AS THAT CHANCE IS REALLY

LOW.

GIVE YOU AN EXAMPLE OF A VERY

VERY PRESTIGES MEDICAL

INSTITUTION THAT'S NOT THAT FAR

NORTH OF THE NIH.

I WON'T NAME WHAT MEDICAL

INSTITUTION IT IS.

I WENT UP THERE ONE TIME TO TALK

TO THEIR IRBs ABOUT

BIOSPECIMEN RESEARCH AND I TRIED

TO ARGUE AS I'M GOING TO TRY TO

ARGUE HERE I'M NOT THAT WORRIED

ABOUT THE RISK OF THIS RESEARCH

WHEN IT'S DONE RIGHT.

AT THE END OF IT ONE OF THE IRB

MEMBERS GOT UP AND SAID, I DON'T

KNOW WHAT I'M TALKING ABOUT.

THIS RESEARCH IS ALWAYS MORE

THAN MINIMAL RISK.

AND I SAID WHY WOULD YOU POOL

THINK IT'S MORE THAN MINUTE --

POSSIBLY THINK IT'S MORE THAN

MINIMAL RISK.

HE GAVE ME AN INTERESTING

CONVOLUTED STORY YOU CAN GET

SOMEBODY'S SPECIMEN, SOMEBODY

CAN BREAK INTO THE ROOM AND GET

INTO THE COMPUTER AND GET THEIR

INFORMATION AND THEY HAVE THIS

CRAZY MUTATION AND IT TURN OUT

THAT PERSON KNOWS SOMEBODY WHO

WORKS FOR INSURANCE COMPANIES

WHO EMPLOYS THE PERSON AN EMPLOYEES THE PE
RSON AND HIS

FATHER AND WENT ON AND ON.

AND ENDED UP BEING REALLY HURT.

THAT'S POSSIBLE ISN'T IT.

I SAID I THINK THAT IS POSSIBLE.

THEY SAID THEREFORE IT'S MORE

THAN MINIMAL RISK.

IT'S NOT, RIGHT, IF THAT

CONVOLUTED STORY THE CHANCES OF

IT BEING REALIZED IN THE WORLD

WE LIVE IN IS REALLY LOW IT

STILL MIGHT BE MINIMAL RISK.

THAT'S THE MISTAKE THAT PERSON

MADE.

THAT'S THE POINT.

YOU CAN EVEN BE DEATH AND --

WHAT'S REALLY LOW IS AS I

MENTIONED THERE ARE DIFFERENT

WAYS OF CRUNCHING THESE MRTS.

ONE ESTIMATE WE'VE COME UP WITH

IS THE RISK OF DEATH, HOPEFULLY

WITH THE PARENTS IN THE AUDIENCE

I'M NOT SCARING YOU TOO MUCH.

BUT ON AVERAGE EVERY TIME YOU

PUT YOUR KID IN THE CAR AND GO

DRIVING SOMEWHERE, THERE'S

PROBABLY SOMEWHERE AROUND A ONE

AND A QUARTER MINUTE CHANCE THAT

YOUR CHILD'S GOING TO DIE

UNFORTUNATELY.

THAT'S PROBABLY A DECENT AVERAGE

GUESS.

SO GIVEN THAT, WHAT IT SUGGESTS

IS ONE WAY TO EVALUATE WHETHER

OR NOT THESE RISKS ARE MINIMAL

IS THE CHANCE OF SOMETHING

REALLY BAD HAPPENING IN THE

RESEARCH HIGHER OR LOWER THAN

THAT FIGURE.

SO NOW GETTING DIRECTLY TO

BIOSPECIMENS RESEARCH.

WHAT ARE THE RISKS.

WELL THE FIRST RISK AT LEAST IN

SOME CASES THE RISK OF OBTAINING

THE SAMPLE IN THE FIRST PLACE, I

DON'T KNOW IF PEOPLE DO MUCH

BIOBIOPSY RESEARCH, WE CAN TALK

ABOUT THAT, THERE ARE RISKS

THERE DEPENDING YOUR BIOPSY AND

OBVIOUSLY IT CAN GET A LOT

RISKIER.

FOR THE MOST PART BLOOD SAMPLES

ARE TAKEN BY NEEDLE STICKS OR

PROCEDURES LESS RISKY, SWABS,

MAYBE YOU ALREADY HAVE SOME LEFT

OVER SAMPLES, MAYBE YOU ALREADY

HAVE A LINE THAT'S BEEN PUT IN

FOR CLINICALLY INDICATED REASONS

YOU CAN JUST GET THE BLOOD FROM

THAT LINE.

FOR MOST OF THESE PROCEDURES,

EITHER THERE IS RISKY AS A

SINGLE NEEDLE STICK OR THEY'RE

LESS RISKY THAN A SINGLE NEEDLE

STICK.

AND AS WE MENTIONED BEFORE,

SINGLE NEEDLE STICKS ARE BY

DEFINITION MINIMAL RISK.

AND SO WHAT THAT SUGGESTS IS AT

LEAST MOST, AGAIN LEAVING ASIDE

BIOPSIES OF ORGANS, MOST METHODS

FOR OBTAINING SAMPLES FOR

BIOSPECIMENS RESEARCH ARE BY

DEFINITION MINIMAL RISKS.

WHAT ARE THE OTHER RISKS.

LET ME KNOW IF I GOT THIS LIST

RIGHT.

HERE ARE SOME OF THE OTHER RISKS

OF STORAGE AND FUTURE USE, RISKS

BEYOND ACTUAL OBTAINING OF THE

SAMPLE.

IN SOME CASES THESE ARE RISKS OF

STIGMA.

IT'S WHAT I CALL A CONTRIBUTION

RISK AND THERE'S ALSO PRIVACY

AND CONFIDENTIALITY.

THOSE ARE THE CONCERNS THE WOMAN

WAS WORRIED ABOUT AT THAT

INSTITUTION, SOMEBODY CLIMBING

UP THE SIDE OF THE BUILDING TO

GET INTO SOMEBODY'S LAB.

SO TO SAY SOMETHING QUICKLY

ABOUT CONTRIBUTION RISKS.

I HAVE EXAMPLES OF ABORTIONS.

ONE OF THE MISTAKES, I THINK A

LOT OF PEOPLE THINK BIOSPECIMENS

RESEARCH IS RISKIER THAN IT

REALLY IS.

I THINK THAT'S A MISTAKE PEOPLE

MAKE ON ONE SIDE.

ON THE OTHER HAND I THINK PEOPLE

WHO ARE SORT OF DEFENDERS OF

BIOSPECIMENS RESEARCH WILL OFTEN

ARGUE THE ONLY RISKS ARE

PHYSICAL RISKS.

SO IF YOU HAVE A SAFE METHOD OF

GETTING A SPECIMEN AND YOU

PROTECT PEOPLE PRIVACY

CONFIDENTIALITY, THERE ARE NO

OTHER CONCERNS.

AND I THINK THAT OVERLOOKS A

REALLY IMPORTANT OTHER ASPECT OF

BIOSPECIMENS RESEARCH WHICH

ROUGHLY IS THE IDEA THAT IF YOU

TAKE MY SAMPLES AND YOU USE IT

FOR FUTURE RESEARCH, THERE'S AN

IMPORTANT SENSE IN WHICH AS A

RESULT OF THAT RESEARCH I'M

CONTRIBUTING TO WHATEVER

RESEARCH YOU DO.

AND I THINK AND A LOT OF PEOPLE

I THINK SHARE THIS INTUITION

THAT WHEN THAT HAPPENS, WHAT

RESEARCH YOU DO WITH MY SAMPLE

CAN HAVE AN INFLUENCE ON MY

INTERESTS IN A WAY WE COULD TALK

ABOUT IF PEOPLE ARE INTERESTED.

BASICALLY THE ROUGH IDEA HERE IS

ROUGH IMPLICATION IS THAT IT'S

NOT A GOOD IDEA.

IT ACTUALLY CAN HARM PEOPLE IF

YOU USE THEIR SAMPLES FOR TYPES

OF RESEARCH THAT THEY FIND VERY

OBJECTION KNOWLEDGE.

SO RESEARCH THAT CONFLIKDZ WITH

THEIR -- CONFLICTS WITH THEIR

FUNDAMENTAL VALUES.

DEPENDING ON THE PERSON AT LEGAL

SOME DATA SUGGESTS IN THE U.S.

AT LEAST THERE ARE A LOT OF

PEOPLE THAT ARE OPPOSED TO

RESEARCH ON APPROVED METHODS OF

ABORTION.

FOR THOSE PEOPLE THE RESEARCH

COULD BE PROBLEMATIC.

A LOT OF PEOPLE ARE OPPOSED TO

RESEARCH ON NEW WAYS TO CLONE OR

ACTUAL CLONING OF HUMAN BEINGS.

SO FOR THEM THAT TYPE OF

RESEARCH, I DON'T KNOW IF

ANYBODY'S DOING IT, BUT IF THEY

WERE THAT WOULD BE PROBLEMATIC

AS WELL.

I THINK THESE ARE AT LEAST THE

MAIN RISKS OF RESEARCH WHEN

YOU'RE TALKING ABOUT STORING AND

USING THE SAMPLES IN THE FUTURE.

SO I TAKE IT AT LEAST THE VAST

MAJORITY OF RESEARCH THAT PEOPLE

ARE DOING IS FAIRLY

NON-CONTROVERSIAL.

MOST PEOPLE AREN'T DOING

RESEARCH ON APPROVED METHODS FOR

ABORTION.

MOST PEOPLE AREN'T DOING

RESEARCH ON WAYS TO CLONE HUMAN

BEINGS.

MOST OF IT'S FAIRLY

NON-CONTROVERSIAL AND SO I THINK

IN THOSE CASES LET'S ESSENTIALLY

NO CONTRIBUTION RISKS AND ALSO

ESSENTIALLY NO RISKS FOR STIGMA.

SO WHAT THAT LEAVES US IS THE

RISKS OF PRIVACY AND

CONFIDENTIALITY.

AND MY EXPERIENCE AT LEAST ON

THE PROTOCOLS THAT I REVIEW IS

THAT RESEARCHERS TEND TO DO A

VERY GOOD JOB BECAUSE THEY ARE

FORCING THEM TO.

THE INVESTIGATORS IN THE END DO

A VERY GOOD JOB OVE OF PROTECTING

PRIVE Z THEY HAVE CODPRIVACIES.

THE CODES ARE IN A LOCKED ROOM

AND DO A PRETTY GOOD JOB OF

PROTECTING PEOPLE IN THIS

REGARD.

HERE'S THE BASIC IDEA IS THAT

GENETIC TESTING GETS DONE IN THE

CLINICAL SETTING FOR KIDS.

ALMOST EVERY STATE I KNOW OF HAS

SOME REQUIREMENTS FOR KIDS TO BE

TESTED.

SO THAT'S A ROUTINE PROCEDURE.

SO THERE'S RISKS TO PRIVACY AND

CONFIDENTIALITY FROM THAT

INFORMATION BEING STORED IN THE

CLINICAL SETTING.

THAT'S A ROUTINE PROCEDURE.

AND MY ASSUMPTION IS THAT MOST

RESEARCH DATA IS BETTER

PROTECTED THAN MOST CLINICALLY

OBTAINED DATA.

IF THAT'S RIGHT IT SUGGESTS THAT

THESE RISKS ARE ALSO CLEARLY

MINIMAL SINCE THEY ARE LOWER

THAN THOSE RISKS IN THE CLINICAL

SETTING FROM A ROUTINE

PROCEDURE.

I DON'T KNOW OF ANY REALLY GOOD

DATA, I WOULD BE REALLY

INTERESTED, I DON'T KNOW IF

ANYBODY'S COME UP WITH THIS DATA

YET BUT AT LEAST ANECDOTALLY

THERE ARE HUNDREDS OF MILLIONS,

PROBABLY MORE THAN NOW HUNDREDS

OF MILLIONS OF STORED SAMPLES IN

LABS IN THE U.S. AND AROUND THE

WORLD.

I AT LEAST DON'T KNOW OF ANY

CASES WHERE SOMEBODY HAS GONE

INTO ONE OF THOSE LABS AND THE

RESEARCHER'S GOTTEN SOMEBODY'S

INFORMATION AND DONE SOMETHING

TO THEM THAT REALLY HARMED THAT.

THAT SUGGESTED TO SUPPORT THIS

CLAIM.

USING THE NUMBERS I HAD FROM

DRIVING NOTICE GIVEN THAT NUMBER

OF SAMPLES IN ORDER FOR THIS

RESEARCH NOT TO BE MINIMAL YOU

NEED MORE THAN JUST A COUPLE

INSTANCES OF SERIOUS HARM.

YOU PROBABLY NEED 30 OR 40

REALLY BAD HARMS OR AT LEAST 300

OR 400 THAT I CALL MODERATE

HARMS.

LET'S SORT OF INDIVIDUAL RISKS,

INDIVIDUAL PROCEDURES.

AS I MENTIONED ONE ONCE YOU DO THAT

I'M ARGUING THESE ASPECTS OF

BIOSPECIMENS RESEARCH WITH

CHILDREN ARE MINIMAL.

WE ALSO HAVE TO AGGREGATE THOSE

RISKS.

WHAT I BASICALLY TRY TO ARGUE

SEE IF I CONVINCE PEOPLE WITH

QUESTIONS IS EACH ONE OF THOSE

COMPONENTS IS CLEARLY MINIMAL

RISK.

SO I TAKE IT IF YOU'VE GOT THREE

RISKS ALL OF WHICH ARE CLEARLY

MINIMAL IN A SENSE EVEN BELOW

MINIMAL IDENTIFY THINK PUTTING

THREE OF THEM TOBACCO YOU STILL

HAVE A MINIMAL RISK.

THERE'S SOME POINT AT WHICH A

NUMBER OF MINIMAL RISK

PROCEDURES BECOMES MORE THAN

MINIMAL RISK.

HONESTLY I DON'T KNOW WHERE THAT

NUMBER IS.

I DON'T KNOW IF IT'S TEN OR 20

OR 50 BUT I THINK IT'S PRETTY

CLEAR AND WE CAN TALK ABOUT

THAT.

IT'S NOT FREE.

THAT SUGGESTS THAT THIS RESEARCH

EVEN IN AGGREGATE IS MINIMAL

RISK.

THAT'S THE FIRST PART.

I'M GOING TO TALK ABOUT

PERMISSION, AWE ISN' ASSENT AND DISSENT.

THIS IS MINIMAL RISK UNDER THE

U.S. REGULATIONS THAT IMPLIES

YOU SHOULD GET THE PERMISSION OF

ONE PARENT WHEN MINIMAL RISK

RESEARCH.

THERE ARE A COMA COUPLE EXCEPTIONS WE

CAN TALK ABOUT TWO OF WHICH I

NOTED HERE.

ALSO THE U.S. REGULATIONS

REQUIRE WHAT IS CALLED THE

ASSENT.

THAT'S ALSO DEFINED AS THE

AFFIRMATIVE AGREEMENT TO

PARTICIPATE IN RESEARCH.

YOU HEAR THE QUALIFICATION IS

IT'S CHILDREN WHO ARE CAPABLE OF

PROVIDING ASSENT WHICH IS A TERM

THAT THE REGULATIONS DON'T

DEFINE.

SO IT'S NOT CLEAR EXACTLY WHO

ISN'T CAPABLE OF GIVING ASSENT.

WE DID ANOTHER SURVEY A COUPLE

YEARS AGO OF IRB CHAIRS TO TRY

TO FIGURE OUT WHAT THEY THINK

ABOUT ASSENT.

WHAT WE FOUND OUT IS ABOUT HALF

OF THEM JUST LEAVE IT POP TO THE

INVESTIGATORS.

AND -- UP TO THE INVESTIGATORS

AND THE OTHERS USE AN ARBITRARY

AGE.

THEY JUST PICK AN AGE.

THE PROBLEM IS HERE PEOPLE USE

DIFFERENT AGES.

YOU NEED ANOTHER BROAD SPECTRUM

OF PRACTICE OF CHILDREN CAPABLE

TO GIVE ASSENT.

I'LL COME BACK AND GIVE A

SUGGESTION WHAT IS ROUGHLY THE

RIGHT AGE.

IN TERMS OF PROCESS TYPICALLY

THE WAY THIS IS DONE YOU GET THE

PARENT'S PERMISSION AND THE

CHILD TOGETHER.

YOU GET THEM BOTH IN THE SAME

ROOM AND YOU EXPLAIN THE STUDY

TO BOTH IT WAS OF THEM AND YOU

GET THEM BOTH TO SAY YES.

THERE'S NOT A LOT OF EMPIRICAL

DATA.

I WOULD LIKE TO SEE MORE ON THAT

APPROACH.

IF YOU LOOK AT IT MOST PEOPLE

THINK THEY'RE COMFORTABLE WITH

THAT, PARENTS SEEM COMFORTABLE

DOING IT TOGETHER AND THE

CHILDREN SEEM TO BE COMFORT.

THERE ARE A FEW STUDIES SEEM

THAT IN THAT CASE CHILDREN MEUT MIGHT

FEEL ABLE TO SAY NO.

WE MIGHT RAISE WARNING SIGNS

CONSIDERING ASKING SOME CHILDREN

INDEPENDENTLY OF THE PARENT IN

SOME CASES WHERE YOU THINK THEY

ARE BEING PRESSURED BY THE

PARENTS.

DISSENT.

U.S. REGULATIONS TALK ABOUT

ASSENT AND AFFIRMATIVE

AGREEMENT.

WHAT THEY DON'T TALK IS DISSENT.

THEY DON'T TALK ABOUT

AFFIRMATIVE OR POSITIVE

OBJECTIONS.

NOW IF A CHILD SEEMS CAPABLE OF

ASSENT THEN OBVIOUSLY A DISSENT

IS NOT ASSENT.

ACCORDING TO THE REGULATIONS YOU

HAVE TO TAKE THEM OUT OF THE

RESEARCH.

THE PROBLEM IS THAT REGULATIONS

DON'T COVER CHILDREN WHO ARE

DEEMED TOO YOUNG TO ASSENT.

I THINK THAT'S A PROBLEM.

EVEN A CHILD'S TOO YOUNG TO

ASSENT IF THEY'RE REALLY

STRESSED OUT BY BEING A

NON-BENEFICIAL RESEARCH I THINK

THAT'S A REASON IF YOU CAN'T

ADDRESS THE DISTRESS.

THAT'S A REASON TO TAKE THEM OUT

OF THE RESEARCH.

NOW WHETHER OR NOT DISSENT IF

YOU HAVE A BIOSPECIMENS STUDY

TAKING SAM MEMORANDUM OVER TIME

MAYBE THE ONLY CASE I COULD

THINK OF WHERE DISSENT MIGHT

REALLY BE AN ISSUE IN THIS

CONTEXT.

ANOTHER THING TO POINT OUT IS

TYPICALLY AT LEAST WHEN WE THANK

YOU ABOUT ADULTS, WE GET

PERMISSION AND WE GIVE

INFORMATION IN THE SAME PROCESS.

YOU EXPLAIN THE STUDY TO THEM

AND THEN YOU ASK THEM WHETHER OR

NOT THEY SAY YES.

THAT MAKES SENSE WHEN YOU HAVE

SOMEBODY WHO YOU GIVE CONSENT OR

ASSENT.

IF WE BUNDLE THEM TOGETHER ALL

THE TIME IS WHEN WE HAVE

CHILDREN WHO AREN'T CAPABLE OF

ASSENT.

SO FOR INSTANCE IRBs THEY HAVE

AN ASSENT FORM.

IF YOU GIVE THAT ASSENT FORM

ONLY TO CHILDREN WHO ARE CAPABLE

OF ASSENT.

IF YOU ASK A FIVE OR SIX YEAR

OLD WHO IS NOT CAPABLE OF ASSENT

THEY DON'T GET THAT FORM THEY

MIGHT NOT GET ANY INFORMATION

ABOUT THE STUDY.

I THINK THAT'S A PROBLEM AND

IT'S IMPORTANT TO SEPARATE THESE

TWO REQUIREMENTS AND MAKE SURE

AGE APPROPRIATE IS GIVEN TO ALL

CHILDREN.

I'LL JUST COME BACK TO THIS

QUICKLY.

THIS IS THE BEGINNINGS OF AN

ARGUMENT.

IMPORTANT PEOPLE ARE INTERESTED.

BUT ASSUMING THAT WE RESPECT

DISSENT, AT LEAST SUSTAINED

DISSENT AND ASSUMING WE GIVE

AGE-APPROPRIATION, THEN I THINK

AND I THINK THE DATA SUPPORTS

THIS THAT WE SHOULD USE AS THE

AGE FOR AWE CEP ASSENT BASICALLY THE

UPPER END OF THE REASONABLE

RANGE WHICH IS ROUGHLY SOMETHING

LIKE 12 TO 14.

I THINK THAT'S ACTUALLY THE

RIGHT AGE FOR ASSENT.

I WILL NOTE FOR MOST PEOPLE WHO

WORK A PEDIATRICS ETHICS THEY

THINK THAT'S TOO HIGH.

I THINK THE DATA AND ARGUMENT

SUGGESTS THAT'S ACTUALLY THE

RIGHT AGE.

LAST THING I'LL MENTION BUT I

THINK OTHER PEOPLE ARE GOING TO

TALK ABOUT THIS.

THIS IS THE HARD PROBLEM AND I

DON'T KNOW WHAT TO SAY ABOUT IT

SO I'M GLAD THEY WILL WHICH IS

WE'RE TALKING ABOUT PEDIATRIC

BIOSPECIMENS RESEARCH.

MOST CHILDREN AT SOME POINT

BECOME ADULTS AND THEN THE

QUESTION IS WHETHER OR NOT ONCE

THEY'RE ADULTS YOU SHOULD GO

BACK AND GET THEIR ASSENT TO

CONTINUE TO HOLD ON TO THE

SPECIMENS AND USE THEM FOR

FUTURE RESEARCH.

SO THE ANSWER TO THAT QUESTION I

THINK IS COMING UP IN A LITTLE

WHILE RIGHT HERE.

SO JUST A QUICK SUMMARY.

JUST DO ANY KIND OF RESEARCH

INCLUDING BIOSPECIMENS RESEARCH

WITH CHILDREN ONLY WHEN IT'S

VALUABLE.

YOU SHOULD MINIMIZE THE RISKS,

EVALUATE BOTH THE RISKS OF THE

INDIVIDUAL INTERVENTION IN THE

STUDY AND ALSO THE AGGREGATE

RISKS OF THE INTERVENTION AS A

WHOLE OBTAINED IN MOST CASES

PARENTAL PERMISSION.

ASSENT OF CHILDREN CAPABLE OF

PROVIDING IT, RESPECT CHILDREN'S

DISSENT AND PROVIDE

APPROPRIATION TO CHILDREN.

SO THAT'S IT.

I THINK WHAT WE'RE GOING TO DO

IS TAKE AT LEAST A COUPLE

QUESTIONS AFTER EACH TALK SO I

THINK I HAVE ABOUT SEVEN MIS.

SO I DON'T KNOW IF ANYBODY HAS

QUESTIONS.

AND IT'S STREAMED SO I THINK, IS

THIS RIGHT IT'S ONLY GOING TO

PICK IT UP IF THEY GO TO THE

MICS.

SO IF YOU HAVE A QUESTION,

EITHER IF YOU GO TO A MIC OR

I'LL REPEAT IT BEFORE WE GET IT.

>> SO THE QUESTION BASICALLY IS

A QUESTION ABOUT WHEN SHOULD YOU

DO RESEARCH IN CHILDREN AND WHEN

SHOULD YOU INSTEAD DO YOUR

RESEARCH IN ADULTS.

HOW DO YOU COMPARE RESULTS FROM

CHILDREN AND PARENTS AND ADULTS

AND HOW DO YOU DECIDE WHAT

RESEARCH YOU CAN DO ON SAMPLES

AND SHOULD IT BE LIMITED TO

CERTAIN SORTS OF CONDITIONS.

LET ME TRY TO ANSWER THOSE AND

SEE IF I GOT IT ALL.

I THINK IN GENERAL I AGREE IF

YOU CAN DO A STUDY IN PEOPLE WHO

CAN GIVE CONSENT YOU SHOULD DO

IT THEN RATHER THAN PEOPLE WHO

CAN'T GIVE CONSENT.

IF YOU CAN DO YOUR STUDY IN

COMPETENT ADULTS IT'S TYPICALLY

BETTER TO DO IT IN COMPETENT

ADULTS THAN TO DO IT IN

CHILDREN.

NOW IF THERE'S A REASON TO DO IT

IN CHILDREN THERE'S SOME

INTERESTING INFORMATION YOU'RE

GOING TO GET FROM CHILDREN YOU

CAN'T GET FROM ADULTS OR YOU

WANT TO MAKE COMPARISONS BETWEEN

ADULTS AND CHILDREN, THEN THAT

TYPICALLY IS A GOOD REASON TO DO

IT IN CHILDREN AND YOU SHOULD BE

ABLE TO DO IT IN CHILDREN

ASSUMING YOU MEET ALL THE

REQUIREMENTS.

VALUABLE AND MEET ALL THE RISK

REQUIREMENTS OF PEDIATRIC

RESEARCH.

SO THEN I THINK IN THOSE CASES I

THINK DOING IT IN CHILDREN IS

PROBABLY A GOOD IDEA.

I THINK THIS IS A DIFFERENT

TOPIC A LITTLE BIT BUT I THINK

THERE'S A BIG QUESTION HERE

ABOUT WHEN YOU GET CONSENT FOR

BIOSPECIMENS RESEARCH BASICALLY

THE QUESTION IS WHAT INFORMATION

SHOULD YOU GIVE TO PEOPLE.

THERE'S BEEN A BIG DEBATE AND

LOT OF PEOPLE, THERE ARE A

DIFFERENT VIEWS ON THIS, A LOT

OF PEOPLE HAVE WHAT I CALL A

MENU APPROACH WHICH IS WHAT

YOU'RE SUPPOSED TO DO IS GIVE

PEOPLE DIFFERENT CHECK BOXES

LIKE CAN WE USE YOUR SAMPLES FOR

FUTURE RESEARCH ON CANCER.

CAN WE USE IT FOR FUTURE

RESEARCH A DIE BOATS, O DIABETES.

I THINK THAT'S A WELL

INTENTIONED APPROACH.

I THINK IT'S A MISTAKE THOUGH.

I THINK IT'S A MISTAKE BECAUSE I

DON'T THINK IT HELPS THE PEOPLE

GIVING THE CONSENT AND I THINK

IT CAN HINDER THE RESEARCH IN A

LOT OF WAYS.

YOU THOUGHT YOU'D ONLY WANT TO

DO RESEARCH A CANCER AND

DIABETES WITH THE SAMPLES AND

FIVE YEARS LATER SOMEBODY FINDS

A LINK BETWEEN THAT AND SOME

OTHER DISEASE YOU NEVER THOUGHT

OF.

NOW WHAT DO YOU DO.

IF I'M ON THE IRB AND YOU SAID

WE'RE ONLY GOING TO USE IT FOR

DIABETES OR CANCER AND NOW YOU

COME BACK AND SAY YOU WANT TO

USE IT FOR SCHITZOPHRENIA I'LL

SAY YOU CAN'T, YOU ONLY TOLD US

YOU WOULD USE IT FOR THESE TWO

DISEASES.

I THINK THE RESPONSE TO THAT IS

NOT TO LIMIT THE CONSENT THAT

WAY BUT BASICALLY TO GET WHAT I

CALL ONE TIME GENERAL CONSENT

WHICH IS AT THE TIME YOU OBTAIN

THE SAMPLES AT THE PERSON.

WE PLAN TO USE THIS IN FUTURE

RESEARCH IN GENERAL.

DIFFERENT DISEASES, DIFFERENT

POPULATION.

AND YOU SHOULD ONLY AGREE IF YOU

THINK THAT'S OKAY.

THE DATA SUGGESTS A VAST

MAJORITY OF PEOPLE DO THINK

THAT'S OKAY AND IT SHOULDN'T

LIMIT VERY MUCH WHAT YOUR

CONTENT REALLY IS.

SO I THINK A LOT OF ADDRESSING

THAT PROBLEM ABOUT WHAT THE

RESEARCH IS LIMITED TO IS HAVING

BROAD CONSENT AT THE BEGINNING

AND JUST AVOIDING THE WHOLE

ISSUE.

>> THANK YOU SO MUCH FOR YOUR

TALK.

YOU TALKED ABOUT SORT OF

ASSESSING THE PARENTAL ASSENT

BASED ON ONE PARENT.

WHAT HAPPENS WHEN THE PARENTS

DISAGREE?

>> WHEN THE PARENTS DISAGREE,

YOU HAVE A PROBLEM.

ONE THING YOU CAN DO, THERE'S A

THIS-HOUR CONSULTATION SERVICE

AVAILABLE TO ALL EMPLOYEES AT

THE CLINICAL CENTER.

YOU COULD CALL THAT.

YOU MIGHT BE LUCKY ENOUGH TO GET

SARA AND SHE COULD HELP YOU WITH

IT.

SARA'S ON CALL RIGHT NOW.

I THINK THE BASIC VIEW IS IT'S

SIMILAR TO HAVE SOMEBODY IN THE

ICU AND YOU HAVE ONE SURROGATE

AND THEY SAY DO X BUT EVERYBODY

ELSE IN THE FAMILY IS THERE AND

SAY DO Y.

IN MOST CASE YOU TRY REALLY HARD

TO GET EVERYBODY TO AGREE.

YOU WORK REALLY HARD AT THAT.

IF YOU CAN'T GET THEM TO AGREE,

THEN I THINK CALL A CONSULT IS

ONE POSSIBILITY.

ANOTHER POSSIBILITY I THINK IN

RESEARCH SETTING TYPICALLY, THE

DEFAULT IS NO.

SO IF ONE PARENT SAYS NO AND ONE

PARENT SAYS YES, I THINK THE

DEFAULT THEY SHOULD GO WITH NO

UNLESS THAT RESEARCH OFFERS SOME

REALLY IMPORTANT CHANCE OF

BENEFIT TO THE CHILD.

IF IT DOES THAT THEN I THINK YOU

SHOULD DEFINITELY CALL THEM.

>> YOU ALSO MENTIONED USING SORT

OF A SUBJECTIVE BASIS OF A

NORMAL HEALTHY CHILD.

BUT A LOT OF THIS RESEARCH IS

FOR THE BASIS OF SICK CHILDREN.

>> RIGHT.

>> SO I'VE HEARD COMMENTS FROM A

LOT OF PARENTS OF SICK CHILDREN

AND CHILDREN WITH RARE DISEASES

AND SERIOUS DISEASES TALK ABOUT

THEIR CONCERNS ABOUT USING THAT

KIND OF A BASIS BECAUSE THEIR

CHILDREN ARE SICK AND THEY WANT

KIND OF A RECOGNITION OF THE

FACT THAT THERE'S A NEED FOR

SOME ATTENTION TO THE FACT

THAT --

>> THOSE CONDITIONS, YES.

THAT'S REALLY IMPORTANT.

AND I THINK RESEARCH IN RARE IS

REALLY IMPORTANT.

SO THAT BASICALLY USING THE

STANDARD OF THE LIVES OF AVERAGE

ORDINARY CHILDREN, THAT'S NOT

SUPPOSED TO BE A STATEMENT FOR

WHAT RESEARCH YOU CAN DO.

THAT'S JUST THE STANDARD FOR

SETTING THE BAR OF WHAT RISKS

COUNT AS MINIMAL AND WHAT RISKS

COUNT AS MINIMAL.

YOU'RE SUPPOSED TO LOOK AT THE

RISKS THAT THOSE CHILDREN FACE.

AND THEN THE QUESTION, SO IF YOU

WANT TO DO A STUDY OF A REALLY

RARE DISEASE, YOU WANT TO SAY

OKAY IS THIS MINIMAL RISK OR

NOT, WHAT YOU DO IS FIND OUT

WHAT THE RISKS ARE THAT THAT

RESEARCH IS GOING TO POSE TO

THOSE KIDS WITH A RARE DISEASE,

GET A SENSE FOR WHAT THAT LEVEL

OF RISK IS AND THEN ASK YOURSELF

IS THAT LEVEL OF RISK LESS THAN

OR GREATER THAN THE LEVEL OF

RISKS THAT AVERAGE ORDINARY

CHILDREN FACE IN DAILY LIFE.

THE IDEA THERE IS YOU DON'T WANT

TO ATTACH IT TO THE RISK THAT

SICK CHILDREN FACE.

CHILDREN WITH CANCER WHO GET

REALLY NASTY CHEMOTHERAPY ONCE A

WEEK, YOU DON'T WANT TO SAY LOOK

THEY'RE GETTING REALLY NASTY

CHEMOTHERAPY ONCE A WEEK, I'M

ONLY GOING TO DO A KIDNEY

BIOPSY, THAT'S NEARLY AS BAD

MINIMAL RISK BUT THAT'S WHAT

WE'RE TRYING TO AVOID.

WEIL TAKE TWO MORE AND THEN

WE'LL DO IT LATER.

>> I WANTED TO FOLLOW UP ON THE

LUMBER PUNCTURES IN OUR RESOFT

ABILITY TO HAVE NORMAL PEDIATRIC

CSF IS A HUGE PROBLEM.

COULD YOU TALK IT THROUGH IN A

WAY WE MIGHT ARGUE HEALTHY KIDS

ARE MINIMAL RISK.

>> SO THIS IS REALLY HARD.

AGAIN, I'M PROTECTING

CONFIDENTIALITY.

I WON'T TELL YOU THE PERSON BUT

ONE OF THE SMARTEST PEOPLE WHO I

THINK HAS EVER SERIOUSLY THOUGHT

ABOUT PEDIATRIC RESEARCH ETHICS

IN THIS COUNTRY.

WE HAD A CONFERENCE AND THAT

PERSON HAD RECENTLY UNDERGONE AN

LP AND UNFORTUNATELY HAD A BAD

EXPERIENCE.

THEY SAID IT'S REALLY RISKY.

I HAVE TO THINK I'M SORRY YOU

HAD A BAD EXPERIENCE BUT THAT

DOESN'T PROVE THAT LP IS MINIMAL

RISK.

WE NEED MORE THAN THAT SORT OF

DATA.

THE FIRST THING I WOULD SAY IS

IF IT'S POSSIBLE AND MAYBE YOU

WOULD KNOW BETTER IF THERE'S A

WAY TO GET DATA.

SO FOR INSTANCE I CONSULTED WITH

SOME PEOPLE WHO DO A LOT OF IV

GLUCOSE TOLERANCE TEST AND THEY

HAD IRBs THAT KEPT SAYING THIS

IS MORE THAN MINIMAL RISK YOU

CAN'T DO THIS RESEARCH AND THEY

ASKED ME TO CONSULT WITH THEM.

MY FIRST QUESTION WAS OKAY.

WHEN YOU GO TO THE IRBs HOW

MUCH DATA HAVE YOU PRESENTED TO

THEM ABOUT THE OUTCOMES.

THEY SAID WE NEVER DID THAT.

THEY SAID WELL THEN HOW DO YOU

EXPECT THEM TO MAKE THESE

JUDGMENTS.

THE FIRST THING I WOULD SAY IS

IF YOU CAN FIND THAT I DON'T

KNOW HOW MANY TIMES KIDS ARE

GETTING LPs IN CLINICAL

SETTINGS BUT IF SOME PLACE LIKE

HOPKINS OR ST. JUDE'S OR SOME

PLACES ARE DOING IT A LOT GET

THEIR DATA AND TRY TO PUBLISH IT

WITH YOU AND PROVIDE IT TO

PEOPLE.

WHAT I'VE LEARNED FROM THE

RESEARCHERS IS THE RISK OF THESE

THINGS CAN VARY DEPENDING HOW

IT'S DONE.

USE A SMALLER NEEDLE RATHER THAN

A LARGER NEEDLE AND ALL THESE

SORTS OF THINGS.

IF YOU CAN FIND DATA ON THOSE I

THINK WHAT YOU DO IS YOU FIND

THAT AND THEN YOU COMPARE IT TO

THE DATA WE'VE GOT.

AND MY GUESS PEOPLE I TALKED TO

IS THAT IT WOULD BE MINIMAL RISK

BUT I HAVEN'T SEEN THE DATA TO

MAKE THAT ARGUMENT.

SURE, OKAY.

SO LAST ONE.

>> YOU MENTIONED THAT

PSYCHOLOGICAL RISKS ARE OFTEN

OVERLOOKED IN BIOMEDICAL

RESEARCH.

I WAS WONDERING IF IT'S MORE

COMING TO LIGHT THAT

PSYCHOLOGICAL RISKS IS THIS

BECAUSE THE OTHER RISKS

ASSOCIATED WITH THAT, BIOMEDICAL

RESEARCH CAN BE SO GREAT.

I WAS WONDERING WHAT YOUR

OPINION WAS OR HOW THAT COULD

TRANSLATE TO OTHER PSYCHOLOGICAL

RISKS IN EVERY DAY LIFE.

SO FOR INSTANCE AS A CONSUMER

YOU MAY BE INADVERTENTLY

INCLUDED IN MARKETING RESEARCH

HOW TO MARKET SOMETHING TO

PEOPLE THAT YOU MAY NOT AGREE

WITH.

DO YOU THINK THERE'S ANY

PARALLEL THERE.

>> IT'S A REALLY GOOD QUESTION

THAT WOULD PROBABLY TAKE ME A

LONG ANSWER AND CUT MORE INTO

SARA'S TIME THAN I ALREADY HAVE.

WHICH IS BASICALLY I THINK THAT

I JUST GAVE SORT OF SIMPLISTIC

VIEW OF THE STANDARD WHICH

ROUGHLY SAYS YOU LOOK AT THE

RISKS OF AVERAGE ORDINARY

HEALTHY CHILDREN FACING DAILY

LIFE AND YOU COMPARE IT TO THAT.

IN THE END IT TURNS OUT TO BE A

LITTLE MORE COMPLICATED THAN

THAT ALTHOUGH THE REGULATORS

TONIGHT TELL YOU THIS, THERE ARE

SOME RISKS THAT EVEN AVERAGE

ORDINARY CHILDREN FACE IN DAILY

LIFE BUT I THINK ALL OF US WOULD

AGREE ARE JUST INAPPROPRIATE.

SO DATA SUGGESTS THAT THERE'S A

FAIRLY HIGH CHANCE AVERAGE

ORDINARY KID GETS BULLIED ON THE

PLAYGROUND THAT LEAD TO REALLY

DAMAGING PSYCHOLOGICAL

CONSEQUENCES.

I THINK IT WOULD BE A TERRIBLE

ARGUMENT TO SAY OKAY I'VE GOT

THIS STUDY, I'M GOING TO BULLY

THESE KIDS AND I'M GOING TO FIND

OUT PSYCHOLOGICAL AND I THINK

THERE'S MINIMAL RISK BECAUSE

LOOK THIS IS HAPPENING TO KIDS

ON THE PLAYGROUND EVERY DAY.

IT'S LIKE THE AVERAGE ORDINARY

DAILY LIFE OF A NORMAL KID.

THAT I TAKE IT EVEN THOUGH

LITERALLY SPEAKING IT'S

CONSISTENT WITH THE FEDERAL

REGULATIONS.

I THINK THAT'S A BAD IDEA.

I DON'T THINK IRB SHOULD APPROVE

THAT RESEARCH.

CERTAINLY SHOULDN'T APPROVE IT

AS A MINIMAL RISK.

I THINK WHAT WE NEED TO DO AND

THIS IS WHAT YOUR QUESTION GETS

TO IS WE HAVE TO THINK REALLY

HARD ABOUT BASICALLY I THINK

REALLY WHEN WE MAKE THESE

COMPARISONS WE SHOULD ONLY

CONSIDER A SUBSET OF THE AVERAGE

ORDINARY ACTIVITY.

SO I THINK A CAR RIDE THAT'S WHY

I USE DATA FROM THAT AND NOT

FROM BUG YING BECAUS BULLYING BECAUSE A LO
T OF

THESE ARE APPROPRIATE, SOME OF

THEM AREN'T.

SHOULD I JUST INTRODUCE SARA?

[APPLAUSE]

>> I'M REPRESENTING YAFFA IRAQ

STEI --IRAQ

RUBEN STEIN.

SHE'S AT A CONFERENCE ON

GENOMICS.

I WOULD LIKE TO INTRODUCE OUR

NEXT SPEAKER DR. SAYER AWE HULL.

SHE WILL SPEAK ON PEDIATRIC

BIOSPECIMENS AND INFORMED

CONSENT WHEN CHILDREN REACH

ADULTHOOD.

PREFERENCES AND PRACTICES.

DR. HULL IS A FACULTY MEMBER IN

THE NIH CLINICAL CENTER'S

DEPARTMENT OF BIOETHICS AND

DIRECTS THE NHGRI BIOETHICS CORE

WHICH PROVIDES BIOETHICS

EDUCATION IN CONSULTATION TO

INTRAMURAL RESEARCHERS.

DR. HULL'S RESEARCH IS

RESPONSIVE TO NEW TECHNOLOGICAL

DEVELOPMENTS IN ASSOCIATED

ISSUES THAT OFTEN ARISE IN THE

CONTEXT OF RESEARCH BEING

CONDUCTED AT NHGRI.

CURRENT PROJECT'S FOCUSED ON

ETHICAL ISSUES ASSOCIATED WITH

INCIDENTAL FINDINGS, INFORMED

CONSENT, DATA SHARING AND

RESEARCH INVOLVING NEXT

GENERATION SEQUENCING AND

INDUCED PLURIPOTENT STEM CELLS.

DR. HULL HAS BEEN A MEMBER OF

THE NHGRI INSTITUTION REVIEW

BOARD FOR 13 YEARS AND SERVED AS

ITS VICE CHAIR.

SHE IS ALSO A MEMBER OF THE NIH

STEM CELL ADMINISTRATIVE REVIEW

COMMITTEE AND THE INTERNATIONAL

STEM CELL FORUM ETHICS WORKING

PARTY.

DR. HULL.

>> THANK YOU FOR THAT

INTRODUCTION AND FOR THE

INVITATION TO BE PART OF THIS

PANEL DISCUSSION.

IT'S A VERY TIMELY TOPIC.

PICKING UP WHERE DAVE LEFT OFF,

I'M GOING TO, I THOUGHT THIS WAS

GOING TO BE A CONTRAST TO HIS

PRESENTATION, THAT WAS A MUCH

MORE DATA-INTENSIVE TALK FOR A

FLAWLS IF YOPHILOSOPHER THAN I'M USED TO B
UT

I'M GOING TO LOOK AT ADDITIONAL

DATA THAT MIGHT HELP US GET

FURTHER IN OUR UNDERSTANDING OF

HOW TO APPROACH INFORMED CONSENT

WITH CHILDREN WHO ARE ENROLLED

IN BIOBANKS AND THEN EVENTUALLY

REACH ADULTHOOD.

THE USUAL DISCLAIMERS, THIS IS

JUST ME TALKING HERE.

AND SO TO PICK UP ON A POINT

THAT WAS JUST MADE A MOMENT AGO,

THERE IS INCREASING INTEREST IN

USING CHILDREN'S SAMPLES AND

DATA IN THE CONTEXT OF

BIOBANKING FOR RESEARCH.

TRADITIONAL AREAS OF FOCUS HAVE

BEEN IN CONDITIONS THAT

EXCLUSIVELY EFFECT CHILDREN LIKE

CERTAIN PEDIATRIC CANCERS,

VERTICAL TRANSMISSION OF HIV.

BUT MORE RECENTLY THAT'S BEEN A

RECOGNITION OF THE POTENTIAL

VALUE OF USING SAMPLES,

PEDIATRIC SAMPLES TO LOOK AT AND

LONGITUDINAL STUDIES LOOK AT THE

EARLY INFLUENCES, EARLY

ENVIRONMENTAL INFLUENCES ON

LATER GENE EXPRESSION SO LOOKING

ACROSS THE LIFE SPAN AND THIS

CREATES AN ADDITIONAL SCIENTIFIC

MOTIVATION FOR PEDIATRIC

BIOBANKS.

AND SOME HAVE ARGUED THAT IF

CHILDREN ARE EXCLUDED FROM THIS

RESEARCH, BECAUSE IT'S NOT

DIRECTLY BENEFICIAL TO THEM, IT

COULD LEAD TO NEW CLASSES OF

THERAPEUTIC OR FANS O ORFANS -- INFORMED

CONSENT AND OTHER

CONSIDERATIONS.

SO LOOKING AT THIS CONSENT ISSUE

WHICH YOU NOW UNDERSTAND VERY

WELL, CHILDREN ARE GENERALLY

THOUGHT TO LACK CAPACITY TO BE

ABLE TO CONSENT FOR THEMSELVES.

REGULATIONS AND PHILOSOPHERS AND

OTHERS ARGUE THAT PARENTAL

AUTHORIZATION IS O REQUIRED OR

NECESSARY FOR PEDIATRIC RESEARCH

OR PARTICIPATION.

IN THE CONTEXT OF BIOBANKING

THERE ARE SOME IMPORTANT

QUESTIONS ABOUT THE SCOPE OF

PARENTAL YOU CONSENT.

HOW BROADLY CAN PARENTS CON SENT

TO THE ONGOING USE OF THEIR

CHILDREN'S SPECIMEN FOR WHAT

DURATION AND WHAT PURPOSES.

WHAT IS THE APPROPRIATE ROLE OF

ASSENT AND ONGOING CONTACT WITH

CHILDREN.

SHOULD CHILDREN HAVE A RIGHT TO

DISSENT TO WITHDRAW.

AND ESPECIALLY WHAT HAPPENS WHEN

THEY THEMSELVES REACH ADULTHOOD.

SO I WOULD LIKE TO ARGUE THAT

THERE IS A ROLE FOR EMPIRICAL

DATA TO HELP US PUSH THIS DEBATE

ALONG.

EMPIRICAL DATA CAN REMIND US TO

LOOK AT DIFFERENT STAKE HOLDERS'

PERSPECTIVE AND I HAVE A NICE

AWE LIAWE LIT RATIVE LISTS HERE.

WE HAVE ADULTS, PARENTS OF THOSE

CHILDREN AS WELL AS PROVIDERS

AND RESEARCHERS.

AND THIS CAN GIVE US AN INSIGHT.

ATTITUDES AND CONCERNS ABOUT

THIS RESEARCH CAN HELP US

UNDERSTAND THE ACTUAL OR AT

LEAST THE PERCEIVED IMPACT OF

THIS RESEARCH IN DIFFERENT

POPULATIONS ON THEIR RIGHTS AND

WELFARE.

AND THIS CAN HELP US DEVELOP

MORE NUANCE IN RESPONSE TO

POLICIES.

DATA CAN ALSO GIVE US AN INSIGHT

AS TO ACTUAL FEASIBILITY OF

TRYING OUT SOME OF THESE

PROPOSALS AND WHETHER THEY

ACTUALLY WORK IN PRACTICE.

I'M GOING TO TURN RIGHT TO A

FAIRLY COMMON NORMATIVE CLAIM.

THIS IS A QUOTE FROM ONE TYPICAL

SET OF COMMENTERS ON THIS TOPIC.

MOST AUTHORS ACKNOWLEDGE THE

FACT THAT BIOBANK STORAGE AND

RESEARCH ON PEDIATRIC SAMPLES

CAN BE DONE UNDER A REGIME OF

PARENTAL CONSENT WHERE ONE OF

THE PARENTS OR LEGAL GUARDIAN

GIVES CONSENT FOR THE CHILD.

SO IT WILL BE INTERESTING TO

HAVE SOME DATA ON PARENTAL

PERSPECTIVES IN THIS CASE TO SEE

HOW THIS PLAYS OUT.

AND LANEY ROSS AND HER

COLLEAGUES DID JUST THAT KIND OF

A STUDY.

THEY DESIGNED A STUDY TO LOOK AT

ATTITUDES AND UNDERSTANDINGS OF

POSTPARTUM WOMEN RECENTLY TURNED

MOTHERS.

TO THE ENROLLMENT OF THEIR CHILD

IN A HYPOTHETICAL PEDIATRIC

BIOBANK THAT WOULD UTILIZE THEIR

CORD BLOOD SPECIMENS COLLECTED

AT BIRTH.

SO THEY DID A SURVEY OF 239

WOMEN IN THE UNIVERSITY OF

CHICAGO HOSPITAL SYSTEM.

AND THESE ARE WOMEN WHO HAVE

BEEN APPROACHED TO PARTICIPATE

IN AN ACTUAL OBSTETRIC BIOBANK.

THEY WOULD ASK QUESTIONS ABOUT

HYPOTHETICAL PEDIATRIC BIOBANK.

THE SAMPLE THEY SURVEYED, THE

MAJORITY WERE YOUNG UNDER THE

AGE OF 25, HAVE LESS THAN A

COLLEGE DEGREE, WERE ON PUBLIC

ASSISTANCE AND WERE BLACK OR

AFRICAN AMERICAN.

AND THEY FOUND THAT 48% OF THESE

WOMEN WOULD HYPOTHETICALLY AGREE

TO ENROLL THEIR CHILD IN THIS

KIND OF BIOBANK.

THEIR ASSESSMENT OF THE RISK

LEVEL OF THIS BIOBANK ROUGHLY

MAPPED ON TODAY'S ASSESSMENT

SAYS THE RISK WERE MINIMAL BUT

THERE WASN'T UNIVERSAL AGREEMENT

ON THIS.

A SMALLAL FELT TH SMALL NUMBER FELT THE RI
SKS

WERE MORE THAN MINIMAL AND SOME

THOUGHT IT WASN'T ENOUGH.

THE IRBs REVIEWED THIS

RESEARCH HAVE DETERMINED IT

INVOLVED MINIMAL RISK.

MINIMAL IS THE CORRECT ANSWER IN

THIS CASE.

WHEN ASKED, WHEN THEY ASKED

THESE WOMEN ABOUT THE GOALS OF

THE RESEARCH, 88% SAID THAT THE

GOAL WAS TO ADVANCE SCIENCE.

AND THAT WAS ALSO CONSIDERED THE

CORRECT ANSWER.

BUT NEARLY TWO THIRDS OF THE

WOMEN ALSO STATED THAT THEY

THOUGHT THAT THIS RESEARCH HAD

THE POTENTIAL TO BENEFIT THEIR

ACTUAL CHILD, THAT THERE WAS A

PERSPECTIVE DIRECT BENEFIT FOR

THEIR CHILD AND THAT WAS

CONSIDERED AN INCORRECT ANSWER

IN THE CONTEXT OF THIS BIOBANK.

THE RESEARCHERS ALSO NOTED

JEFERL OTHER MISUNDERSTANDINGS

THAT SOME OF THE -- SEVERAL

OTHER MISUNDERSTANDINGS THAT

WOMEN SEEMED TO HAVE IN THIS

SURVEY THAT RESEARCHERS COULD

GET INFORMATION ABOUT THEIR

CHILD FROM OTHER HEALTHCARE

SETTINGS OTHER THAN THE CHICAGO

HOSPITAL SYSTEM THAT THEY WERE

CURRENTLY BEING IN.

THAT RELATIVE THE FAMILY COULD

GET ACCESS TO THIS DATA AND LAW

ENFORCEMENT COULD GET ACCESS TO

THIS DATA.

SO THE RESEARCHERS CONCLUED,

THEY WERE HEARTENED TO SEE THAT

A SUBSTANTIAL MINORITY, A

SIGNIFICANT NUMBER OF THE WOMEN

IN WHO THEY SURVEYED WOULD

CONSIDER ENROLLING THEIR CHILD

IN A BY OHI BIOCAN BANK THAT WAS

PROPOSED HERE.

THE BASELINE WAS AN IMPORTANT

PIECE OF INFORMATION TO GATHER.

THEY NOTED THAT MANY OF THESE

WOMEN GENERALLY UNDERSTOOD,

SEEMED TO HAVE A RELATIVELY GOOD

UNDERSTANDING OF WHAT WAS

INVOLVED.

BUT THEY ALSO CONCLUDED THAT

THEY WOULD NEED ADDITIONAL

INFORMATION TO BE ABLE TO MAKE

AN INFORMED DECISION.

FOR EXAMPLE THE RESEARCHERS NEED

TO CLEAR LY EXPLAIN TO PARENTS

WHAT INFORMATION THE RESEARCHERS

WOULD HAVE ACCESS AND WHAT

INDIVIDUALS COULD HAVE ACCESS TO

THE DATA GENERATED BY THE

RESEARCH.

THIS KIND OF A STUDY IN A

PARTICULAR CONTEXT WOULD ALLOW

RESEARCHERS TO BETTER TAILOR A

CONSENT PROCESS TO THE

INFORMATION NEEDS OF THAT

PARTICULAR POPULATION.

SO LET'S LOOK AT A SECOND

NORMATIVE CLAIM THAT'S MADE,

WHICH IS THAT IN ADDITION TO THE

NECESSITY OF PARENTAL

AUTHORIZATION, IDEALLY THE

AFFECTED, IN THIS CASE THAT

MEANS THE ENROLLED CHILDREN

THEMSELVES SHOULD BE REACTED

ONCE THEY REACH THE AGE OF

CONSENT OR MATURITY TO ALLOW

CONTINUED RESEARCH ON THEIR

SAMPLES AND DATA.

SO THIS IS A CONTROVERSIAL CLAIM

AND ONE WHICH WILL BE

INTERESTING TO KNOW WHAT THE

GENERAL PUBLIC'S VIEWS ARE ON

THIS.

AND WHETHER THIS IS SOMETHING

THAT THEY WOULD EXPECT IF THEY

WERE GOING TO BE PARTICIPATING

IN A BIOBANK OF THIS SORT.

AND SO DAVID KAUFMANN AND HIS

COLLEAGUE DID A SERIES OF FOCUS

GROUPS TO DRILL DOWN FORWARD

SOME OF THESE QUESTIONS.

THEIR GOAL IS TO IDENTIFY PUBLIC

ATTITUDES AND CONCERNS ABOUT THE

INCLUSION OF CHILDREN IN A

PROPOSED LARGE SCALE COHORT

SETTING.

AND THEY DID 15 FOCUS GROUPS

WHERE THEY LOOKED SPECIFICALLY

AT THE INCLUSION OF CHILDREN AND

ASSOCIATED ISSUES WITH A TOTAL

OF 141 ADULTS IN SIX U.S. CITIES

AND THESE WERE STRAIGHT FID STRATIFIED BY 
VIE

FIRST POPULATION WHICH IS AN

INTERESTING CROSS-SECTION OF

ADULTS IN THE UNITED STATES.

ONE OF THEIR CORE FINDINGS FROM

THESE FOCUS GROUPS, THERE WAS AN

EMPHASIS TIME AND TIME AGAIN ON

INSURING THAT CHILDREN WOULD NOT

PARTICIPATE IN THE COHORT STUDY

AGAINST THEIR WILL.

AND SO THE PEOPLE IN THE FOCUS

GROUPS, THE PARTICIPANTS

GENERALLY THOUGHT THAT PARENTAL

PERMISSION WAS REQUIRED AT

BASELINE BUT THAT ALONE WASN'T

SUFFICIENT.

THAT ASSENT OF THE CHILD HIMSELF

OR HERSELF WAS NECESSARY AT

LEAST WHEN POSSIBLE AND THERE

WAS AN ACKNOWLEDGMENT OF THE

AGE-APPROPRIATENESS, THE NEED TO

LOOK AT THE CHILD'S

UNDERSTANDING.

AND THEN ALSO WE CONTACT THE

CHILDREN WHEN THEY TURN 18.

EITHER TO ALLOW THEM TO GIVE

THEIR CONSENT FOR ONGOING

PARTICIPATION OR AT THE VERY

LEAST TO ALLOW THEM THE

OPPORTUNITY TO WITHDRAW, TO OPT

OUT OF FURTHER STUDY.

AND THIS IS JUST ONE QUOTE FROM

ONE OF THE FOCUS GROUPS THAT

GETS TO THIS IDEA OF

AGE-APPROPRIATENESS.

I THINK IT MATTERS TOO HOW OLD

THE CHILD IS.

IF YOU'VE GOT A YOUNG CHILD, YOU

CAN SAY YES WE'RE GOING TO DO

THIS.

BUT WHEN THEY TURN INTO

TEENAGERS, THEY CAN MAKE THEIR

OWN CHOICE OR THEY'RE GOING TO

DO THIS OR NOT.

SO IT'S INTERESTING THAT A

GROUP, REPRESENTATIVES OF THE

PUBLIC GIVEN SOME BROAD

OPEN-ENDED QUESTIONS CAME UP

WITH THESE VERY NUANCE

DISTINCTIONS ABOUT THE CHILD'S

PERSPECTIVE IN THE COURSE OF

BEING ASKED ABOUT PEDIATRIC

BIOBANKING.

IT'S ALSO INTERESTING THAT THESE

PERSPECTIVES SEEM TO BEAR OUT IN

PRACTICE IN AT LEAST SOME

BIOBANK COHORT STUDIES THAT HAVE

BEEN WRITTEN ABOUT.

SO THERE'S AT LEAST A COUPLE

STUDIES THAT I CAME ACROSS THAT

CHARACTERIZE HOW VARIOUS BIRTH

COHORT STUDIES, THE STUDIES THAT

ARE FOLLOWING CHILDREN FROM THE

TIME THEY'RE BORN THROUGH

ADULTHOOD, HOW THEY ARE ACTUALLY

HANDLING PARENTEDDA PARENTAL PERMISSION AN
D

EVENTUALLY CONSENT FROM THE

CHILD.

IN ALL CASES THESE STUDIES ARE

INITIALLY REQUIRING PERMISSION

FROM AT LEAST ONE PARENT, IN

SOME CASES THE DEFAULT IS THAT

THE PERMISSION IS FROM THE

MOTHER AND ALSO THE FATHER IF

HE'S AVAILABLE.

WHICH IS PA IS AN INTERESTING FRAMING.

NONE ASKED THE PARENTS FOR A

BLANKET OPEN ENDED, THIS IS THE

ONLY TIME WE'RE GOING TO TALK TO

YOU, THE BROADEST POSSIBLE

CONSTRUCTION OF CONSENT.

ASSUME THERE'S GOING TO BE

FREQUENT INTERACTION BETWEEN THE

INVESTIGATORS AND -- YES, THE

INVESTIGATORS AND THE

PARTICIPANTS AND OPPORTUNITIES

TO GET MORE NUANCED CONSENT OVER

TIME THAT STUDIES EVOLVE.

CHILDREN ARE ASKED TO AW ASSENT.

SOME STUDIES DOCUMENT THIS

OCCURS AS YOUNG AS SEVEN OR

EIGHT.

THEY ALL DESCRIBE A DYNAMIC

ASSENT AND -- PROCESS AS THE

CHILDREN MATURE WITH THE STUDY.

SO SUGGESTED AT LEAST IN THE

KIND OF COHORT STUDY WHERE

CHILDREN ARE FOLLOWED OVER TIME

AND WHERE THEY HAVE FOLLOW UP

VISITS AND MAYBE EVEN ARE

CONTRIBUTING ANNUAL SPECIMENS TO

A BIOBANK THAT IT'S FEASIBLE TO

APPROACH CONSENT BOTH FROM A

PERSPECTIVE OF GETTING THE

PARENTS' PERMISSION, GETTING

ASSENT AND THEN EVENTUALLY

GETTING THE CHILD'S CONSENT WHEN

THEY REACH THE AGE OF 18 OR WHEN

THEY'RE READY TO GIVE CONSENT.

THAT BRINGS ME TO THE THIRD

NORMATIVE CLAIM WHICH IS ALMOST

THE COMPLETE INVERSE OF THE

SECOND ONE THAT REQUESTING

CONSENT FROM ADULTS FOR THE

ONGOING USE OF THEIR SPECIMENS

COLLECTED IN CHILDHOOD IS

THOUGHT UNREALISTIC.

NOW THIS WAS STATED AS A GENERAL

CLAIM.

IT MAY HAVE INCLUDED AN

ACKNOWLEDGMENT AS THE DIFFERENT

KINDS OF STUDIES AND DIFFERENT

KINDS OF BIOBANKS AND HOW

THEY'RE STRUCTURED AND THIS

COULD CONCEIVABLY APPLY FOR

EXAMPLE TO STUDIES WHERE

CHILDREN AREN'T FOLLOWED AND

THERE AREN'T THESE GRADUATE

PROGRESSIVE INTERACTIONS WITH

THE INVESTIGATORS OVER TIME.

SO I WAS INVOLVED IN A STUDY

THAT ATTEMPTED TO EXPLORE

ATTITUDES ABOUT THIS EXACT

QUESTION.

ATTITUDES ABOUT HYPOTHETICAL IN

THE CASE AGAIN CONTINUED

RESEARCH WITH PEDIATRIC SAMPLES

AND DATA WHEN PARTICIPANTS ARE

NO LONGER ACTIVELY ENGAGING WITH

RESEARCHERS AND POSSIBLY IN SOME

CASES CAN NO LONGER BE LOCATED.

SO WE SURVEYED NEARLY 1200 ADULT

PATIENTS AT ACADEMIC MEDICAL

CENTERS ACROSS THE U.S., OUR

POPULATION WAS MOSTLY FEMALE,

CAUCASIAN AND OVER THE AGE OF

50.

AND WE PRESENTED PARTICIPANTS

WITH THE FOLLOWING SCENARIO.

I'LL JUST READ IT.

WE ASKED THEM TO CONSIDER THAT

WHEN YOU WERE AN INFANT, YOUR

PARENTS GAVE THEIR PERMISSION

FOR A BLOOD SAMPLE OF YOURS TO

BE USED IN RESEARCH ON

CHILDREN'S HEALTH.

YOUR DOCTOR COLLECTED SAMPLES

FROM HUNDREDS OF INFANTS THIS

WAY.

SINCE THEN YOUR BLOOD SAMPLE HAS

BEEN STORED IN A FREEZER ALONG

WITH A UNIQUE IDENTIFICATION

NUMBER AND SOME BACKGROUND

MEDICAL INFORMATION ABOUT YOU.

SO SOMEWHAT CRUDE OLD FASHION

BIOBANK.

SEVERAL DECADES HAVE PASSED AND

ALL OF THE INTS WHOSE BLOOD

SAMPLES WERE COLLECTED ARE AWE

ADULTS.

THE RESEARCHER NOW WISHES TO

CONTINUE TO USE YOUR SAMPLE FROM

RESEARCH.

THEN WE ASKED THEM A SERIES OF

FOLLOW UP QUESTIONS.

FIRST, HOW CONCERNED WOULD YOU

BE THAT RESEARCH HAD BEEN DONE

WITH YOUR PARENTS' PERMISSION ON

YOUR CHILDHOOD BLOOD SAMPLE.

SO WE CAN'T ACTUALLY, WE WEREN'T

IN A POSITION TO ASK CHILDREN

THIS QUESTION BUT WE ASKED THEM

TO REFLECT BACK ON DECISIONS

THAT THEIR PARENTS MIGHT HAVE

MADE ON THEIR BEHALF.

AND WE FOUND THAT ONLY A THIRD

WERE MODERATELY VERY CONCERNED

AND THAT NEARLY TWO THIRDS WERE

NOT VERY OR AT ALL CONCERN BOARD

OF DIRECTOR THIS SCENARIO.

SECOND, WE ASKED SHOULD THE

RESEARCHER HAVE TO GET YOUR

PERMISSION NOW TO CONTINUE TO

USE YOUR SAMPLE.

THIS IS THE HEART OF THE MATTER.

AND WE SAW THAT THE POPULATION

WE SURVEYED WAS FAIRLY SPLIT

DOWN THE MIDDLE.

46% SAID YES AND 54% SAID NO.

WE WERE INTERESTED TO GO A

LITTLE FURTHER WITH THE PEOPLE

WHO SAID YES TO LOOK AT THE

REALITIES THAT MIGHT BE

ASSOCIATED WITH RECONTACTING

PEOPLE TRACKING THEM DOWN AND

GETTING THEIR AFFIRMATIVE

CONSENT TO CONTINUE DOING

RESEARCH.

SO IF THEY ANSWERED YES, WE

ASKED THEM HOW WILLING FIRST

WOULD YOU BE TO GIVE YOUR

PERMISSION FOR RESEARCHER TO

CONTINUE TO USE YOUR SAMPLE.

YOU'R96% OF THE PEOPLE SAID YES THEY

WOULD BE OKAY, THEY JUST WANTED

TO BE ASKED.

BUT THEN WE ASKED THEM SUPPOSE

THE RESEARCHER COULD NOT LOCATE

YOU, WOULD IT BE ACCEPTABLE FOR

THE RESEARCHER TO USE YOUR

SAMPLE ANYWAY.

AND HERE 44% OF THE PEOPLE WHO

ASKED THAT QUESTION SAID YES.

AND JUST TO CLARIFY.

THIS IS SLIGHTLY LESS THAN A

QUARTER OF THE TOTAL POPULATION,

THE TOTAL SAMPLE IN OUR SURVEY,

WHO CAME DOWN TO ANSWERING THIS

QUESTION, YES, THAT IT WAS 44%

OF THE PEOPLE WHO HAD SAID YES

TO QUESTION TWO.

SO THIS IS A LITTLE BIT

CHALLENGING TO INTERPRET BUT WE

CONCLUDED THAT THESE DATA ARE

CONSISTENT WITH THE NORMATIVE

VIEW THAT WHEN FEASIBLE, ADULTS

SHOULD BE ASKED FOR CONSENT FOR

CONTINUED RESEARCH ON THEIR DATA

COLLECTED DURING CHILDHOOD.

BUT WE HAD TO ACKNOWLEDGE THAT

THERE WAS THIS AREA OF

AMBIGUITY, AND THAT IT MIGHT BE

ACCEPTABLE TO CONTINUE TO

CONDUCT RESEARCH IF ADULTS

CANNOT BE LOCATED.

AND HERE WE THOUGHT SOME

ADDITIONAL DATA COLLECTION AND

PUBLIC ENGAGEMENT MIGHT BE

USEFUL ESPECIALLY AROUND, TO GET

DEEPER INTO AN UNDERSTANDING OF

WHY EXACTLY PEOPLE WERE

OBJECTING TO THIS FURTHER USE.

WHAT WERE THEIR CONCERNS TO BE

CONCERNS TO BE ADDRESSED OR ARE

THERE CERTAIN POPULATIONS WHO

WOULD BE MORE LIKELY TO HAVE

THESE KINDS OF CONCERNS.

NOW INTERESTINGLY, I WAS PLEASED

TO SEE THAT THIS PAPER THAT I

JUST REPORTED ON HAS BEEN CITED

BY A COUPLE OF SUBSEQUENT

PAPERS, BUT THEN I REALIZED THAT

THEY WERE INTERPRETING OUR DATA

IN VASTLY DIFFERENT WAYS.

SO THE PAPER THAT I MENTIONED

EARLIER THAT MADE THE NORMATIVE

CLAIM THAT WE CONTACT THE

UNREALISTIC.

THEY CITED OUR PAPER TO MAKE THE

FOLLOWING POINT.

THE AUTHORS OF ONE STUDY THAT

WAS US CONCLUDED THAT CHILDREN

ARE GENERALLY TRUSTING OF THEIR

PARENTS' DECISIONS AND HAVE

LITTLE CONCERN OVER THE

CONTINUED USE OF THEIR SPECIMENS

AND DATA.

AND THIS IS WHAT LED THEM TO THE

CONCLUSION THAT W RECONTACT IS NOT

ONLY UNREALISTIC BUT

UNNECESSARY.

THE COMMENTER THAT I CITED

EARLIER THAT SAID RECONTACT IS

IDEAL ALSO CITED OUR PAPER TO

PROVIDE EVIDENCE OF THIS.

THEY SAID THERE IS EVIDENCE THAT

THIS, RECONTACT, WOULD BE IN

ACCORD WITH THE DESIRES OF THE

GENERAL POPULATION.

SO I STATE THIS AS A LIMITATION

OF EMPIRICAL, DOING EMPIRICAL

RESEARCH IN GENERAL, AND A

REMINDER TO VIEW ANY DATA

CAUTIOUSLY AND CEPTALLY AN CEPTALLY SKEPTI
CALLY USE

IT AND REACH YOUR DESIRED

CONCLUSIONS.

I'M NOT SURPRISED BY THIS

BECAUSE ACTUALLY OUR DATA WERE

SPLIT IN THEMSELVES, THEY WERE

EQUIVOCAL AND WE WEREN'T QUITE

SURE WHAT TO MAKE OF IT.

I'M PLEASED TO SEE IT HELPS THE

DEBATE MOVE FORWARD BUT I THINK

WE HAVEN'T REACHED ANY FIRM

CONCLUSIONS.

MAYBE THAT MAKES ME A

PHILOSOPHER.

BUT IN SUMMARY, I STILL FEEL

FAIRLY STRONGLY THAT EMPIRICAL

DATA ARE IMPORTANT AND THEY CAN

TELL US SOME THINGS THAT WE

MIGHT HAVE OTHERWISE MISSED.

THEY CAN TELL US WHERE THERE'S

AGREEMENT ABOUT THE IMPORTANCE

OF PRACTICES LIKE RECONTACT AND

THE CONSENT AND WHERE THERE IS

VARIABILITY AND ATTITUDES AND

WHAT'S BEHIND SOME OF THAT

VARIABILITY.

THIS CAN HELP US TAILOR THINGS

LIKE CONSENT, PERMISSION AND

ASSENT PROCESSES, POLICIES AND

PRACTICES FOR PEDIATRIC

BIOBANKING IN A WAY THAT'S MORE

RESPECTFUL AND MORE RESPONSIVE

TO THESE ATTITUDES AND

VARIABILITY AND ATTITUDES.

AND FINALLY IT ALSO CAN TELL US

SOMETHING ABOUT THIS FEASIBILITY

OF VARIOUS PROPOSALS FOR

MANAGING CONSENT AND ASSENT.

AND THERE'S EXAMPLES OF BIOBANKS

THAT LOOK QUITE A BIT

DIFFERENTLY THAN THE EXAMPLES

WHERE I SHARED THERE'S A

ONE-TIME OPT OUT AND NO FOLLOW

UP AND THOSE PROPOSALS SEEM TO

BE MILDLY POPULAR IN THE

POPULATIONS WHERE THEY'RE BEING

STIRREADMINISTERED SUCH AS VANDERBILT

UNIVERSITIES.

THIS WASN'T INTENDED TO BE A

COMPREHENSIVE REVIEW OF DATA AND

EVIDENCE OF WHAT OUR PRACTICES

SHOULD BE BUT MORE OF A PLUG FOR

PAYING ATTENTION TO CONTEXTUAL

SPECIFICS AND SIGHT BY SIGHT

GOALS, RESEARCH GOALS AND

LOOKING AT HOW DIFFERENT

POPULATIONS WILL VIEW THESE AND

LOOKING WHAT KIND OF PRACTICES

ARE FEASIBLE.

AND IT SEEMS AS WHETHER THERE

ARE A NUMBER OF ETHICALLY

ACCEPTABLE APPROACHES THAT ARE

FEASIBLE WHEN WE START TO LOOK

AT THESE DATA.

SO I WILL END THERE, TAKE

QUESTIONS BEFORE TURNING IT OVER

TO CAROL.

[APPLAUSE]

>> THAT'S A GREAT QUESTION.

I'LL REPEAT IT.

SO THE POINT WAS MADE THAT

BIOBANKING THESE DAYS VERY OFTEN

MEANS SEQUENCING AND GENOTYPING

AND PUTTING COMPLETE SEQUENCE

DATA ON SAY CHILDREN INTO DATA

BASES AND THAT THIS MIGHT BE

IRREVERSIBLE WHEN YOU HAVE THIS

INFORMATION OUT THERE IS

POTENTIALLY VIABLE AND POTENTIAL

INFORMATION IS OUT THERE FOR

MANY PEOPLE TO HAVE ACCESS TO.

AND SO WHAT ABOUT THAT CASE.

IT'S INTERESTING.

THERE HAVE BEEN PROPOSALS TO

ALLOW RESEARCHERS TO COLLECT

SAMPLES FROM CHILDREN BUT TO

STOP SHORT FROM DOING THAT KIND

OF BANKING PRECISELY BECAUSE OF

THE CONCERN THAT THIS IS

SOMETHING THAT CHILDREN WILL NO

LONGER HAVE THE ABILITY TO MAKE

UP THEIR MINDS ABOUT ONCE THEY

TURN 18 AND BECOME AN ADULT.

THERE ARE OTHERS WHO ARGUE THAT

THE RISK IS SO MINIMAL TO ANSWER

DAVE'S EARLIER QUESTION.

I ACTUALLY HAVE BEEN ACTIVELY

TRYING TO COLLECT SAMPLES OF

ACTUAL HARMS THAT HAVE OCCURRED

FROM BREACHES OF CONFIDENTIALITY

AND BIOBANKING AND GENETIC

RESEARCH.

I HAVE ZERO EXAMPLES TO SHARE.

LOTS OF SIGNIFICANT CONCERN AND

POTENTIAL BUT NO GOOD CONCRETE

EXAMPLES TO POINT TO.

SO THAT SAID, YOU ALSO WERE

ALLUDING TO THE POSSIBILITY THAT

THERE MIGHT BE VALUE IN MAYBE

LOOKING MORE CLOSELY AT DILL

TERRACE MUTATIONS AND CONTAIN

SOME OF THAT INFORMATION BACK TO

SUBJECTS.

THAT'S AN INTERESTING AND VERY

COMPLICATED SET OF QUESTIONS.

THERE'S A WHOLE SERIES OF

RESEARCH PROJECTS THAT WERE JUST

PUBLISHED THAT I WOULD DIRECT

YOU TO THAT ARE LOOKING CLOSELY

AT THE OBLIGATIONS OF BIOBANKS

TO DISCLOSE INFORMATION ABOUT

INCIDENTAL OR BENEFICIAL FINDING

BACK TO PARTICIPANTS SUSAN WOLF

AND HER COLLEAGUES WOULD BE

WRITING ABOUT THAT.

WE ALSO HAD AN INTERESTING

ETHICS CONSULT HERE LOOKING AT

THE CONTEXT OF PEDIATRIC

BIOBANKING FOR PEDIATRIC

CANCERS, AND CAME UP WITH AN

ALGORITHM TO HELP INVESTIGATORS

FIGURE OUT EXACTLY WHAT KIND OF

RESULTS WOULD COUNT AS ONE

THAT'S SO IMPORTANT THAT YOU

WOULD WANT TO GIVE IT BACK TO A

CHILD OR A PARENT ON BEHALF OF A

CHILD RIGHT AWAY.

AND A VERY LIMITED SET OF

RESULTS BUT THAT STUDY ALSO,

THAT PARTICULAR BIOBANK HAS A

MECHANISM IN PLACE TO NOTIFY

PARTICIPANTS ONCE THEY REACH THE

AGE OF ADULTHOOD AND TO TURN THE

CONTROL OF THE DECISIONS ABOUT

RECEIVING THESE RESULTS OVER

BACK TO THEM AND HAS WORKS OUT A

NUANCE.

SO I THINK I FEEL LOOK MY

ANSWER'S A LITTLE BIT SCATTERED

BUT I THINK YOU'RE RAISING SOME

POINTS.

IT'S A VERY GOOD IDEA FOR

INVESTIGATORS TO BE THINKING

THROUGH WHAT THEIR PURPOSE IS

FOR THE BIOBANK, WHAT THE LONG

TERM GOALS THEY'RE GOING TO HAVE

MECHANISMS FOR HAVING ONGOING

CONTACT WITH PARTS PUNLTSES.

IS THAT JUST TO ADDRESS THE

CONSENT ISSUE, IS THAT TO

ADDRESS GIVING BACK INFORMATION

TO PARTICIPANTS OVER THEIR

CHILDHOOD AND THEN ADULT LIFE

SPAN AND WHAT WOULD THAT

INFORMATION LOOK LIKE AND INTO

WHAT CIRCUMSTANCE THE OBLIGATION

ON THE RESEARCHERS STUB STANLEY

WHEN YOU THINK -- SUBSTANTIALLY

WHEN YOU THINK OF IT THAT WAY.

>> I HAVE QUESTIONS FOR AN HOUR.

THE EXAMPLES YOU GAVE ON DATA

COLLECTION.

I THINK UNADDRESSED IS THE

EVOLUTION OF ETHICS IN ETHICS OF

BIOSPECIMENS.

AND SO I'VE BEEN PRESENTED THAT

SAME SET OF QUESTIONS I WOULD

SAY DID MY PARENTS AGREE BECAUSE

THEY FELT THEY WOULDN'T GET

TREATMENT FOR ME AT THE TIME.

THAT'S ONE ISSUE THAT'S THERE'S

NO TIME FOR.

ANOTHER IS THE ETHICAL ROLE OF

THE FAMILIAL ISSUES.

YOU HAVE A GENETIC DISEASE, IN

CERTAIN CASES MAYBE A RARE

DISEASE.

THERE AREN'T GOING TO BE A LOT

OF OTHER OPPORTUNITIES TO STUDY

IT.

HOW DOES THAT WEIGH INTO THE

DECISION TO INCLUDE YOUR CHILD

OR HAVE A CHILD INCLUDED IN A

RESEARCH STUDY WHERE THE

POTENTIAL BENEFIT IS VERY GREAT

NOT NECESSARILY TO THEM BUT THE

FUTURE, THE FUTURE OF THAT

CHILD'S FAMILY.

AND THEN IN GENERAL, RARE

DISEASES HAS A SPECIAL PROBLEM

ESPECIALLY VERY RARE DISEASES

WITH CONFIDENTIALITY.

THAT IS IF I HAVE THE GENETIC

DATA ON A DOZEN CASES, THEN I

CAN USE THAT TO RULE OUT SO MANY

OTHER CASES THAT I COULD

PROBABLY PINPOINT WHICH CHILD

HAD, WHICH DATA SET WITHOUT EVER

NEEDING TO SAY THE NAME OF

ANYBODY.

SO AS I SAY, THERE'S NO TIME FOR

ALL OF THESE QUESTIONS.

>> I THINK THOSE ARE GREAT

POINTS.

I THINK THE FIRST POINT IS THAT

PARENTS MIGHT FEEL SOME

PRESSURE.

IN FACT YOURS MIGHT HAVE FELT

PRESSURE IN THAT HYPOTHETICAL

SCENARIO TO ENSURE THAT THE

PEDIATRICIAN WOULD CONTINUE TO

TREAT YOU AS A CHILD.

AND TO THE, TENT POSSIBLE, THE

SETTING OF ASKING FOR PARENTAL

PERMISSION.

WE'D LIKE TO BE ABLE TO SEPARATE

THAT COMPLETELY FROM ANY

DECISIONS RELATED TO THE ONGOING

HEALTHCARE OF THE CHILD.

EVEN OTHER RESEARCH PROTOCOLS

AND TREATMENT PROTOCOLS HERE AT

THE NIH WHERE THE DECISION TO

BANK, IF IT'S NOT CRITICALLY AND

CRUCIALLY RELATED TO THE CARE

AND TREATMENT OF THE PEDIATRIC

SUBJECT WOULD LIKE TO MAKE THAT

A SEPARATE DECISION AS POSSIBLE.

BUT PEOPLE DEBATE ABOUT THAT,

AND I THINK THAT CAN SOMETIMES

BE HARD TO DO IN PRACTICE.

AND THEN YOUR SECOND SET OF

QUESTIONS ABOUT OH PRIVACY AND

RARE DISEASES.

THERE ARE SOME ANECDOTAL DATA

THAT I'M AWARE OF WHERE PEOPLE

WHO ARE ATTENDING A RARE DISEASE

CONFERENCE FOR THEIR PARTICULAR

CONDITION HAD WRITTEN THEIR

SPECIFIC MUTATION ON THEIR NAME

TAGS.

THEY COULD GO OUT AND MEET OTHER

PEOPLE WITH THAT EXACT MUTATION

AT THE CONFERENCE AND THAT THE

ORIENTATION TO PRIVACY FOR MANY

PEOPLE WITH RARE DISEASES IS

VERY DIFFERENT THAN WHAT WE

COMMONLY THINK OF AND WHAT

SURVEYS MIGHT BE.

SO I THINK THAT ARGUES FOR DOING

SOME MORE NUANCED RESEARCH ON

THE PRIVACY CONCERNS AND

PERSPECTIVES AND TOLERANCES OF

FAMILIES WITH DIFFERENT KINDS OF

CONDITIONS AND RARE DISEASES.

AND THAT THE VALUE THAT THEY

INVEST IN THIS RESEARCH MIGHT

LOOK A GOOD DEAL DIFFERENT THAN

THE AVERAGE OR THE AVERAGE

HEALTHY PUBLIC WHICH IS WHAT

MANY OF THESE SURVEYS HAVE BEEN

BASED ON.

SO I TAKE THAT POINT AND I THINK

THAT YOU CAN BENEFIT FROM

SIMILAR NUANCE WHICH I THINK HAS

BEEN DONE BUT MORE OF THAT KIND

OF RESEARCH WOULD BE A VALUABLE

WAY TO HELP PROMOTE RESEARCH

THAT'S RESPONSIVE TO THE NEEDS

OF THOSE PARTICIPANTS.

OKAY.

>> SO I WOULD SAY ANOTHER WAY OF

LOOKING AT YOUR DATA ABOUT

SOMETHING LIKE PEOPLE DIDN'T

FEEL COMFORTABLE WITHOUT

RECONSENT BUT 96% SAID THAT IF

YOU ASKED THEM, THEY WOULD SAY

OF COURSE GO AHEAD AND DO THE

RESEARCH.

AND I THINK IT TELLS YOU THAT

PEOPLE WANT TO BE ASKED.

SO ANOTHER, AND WE KNOW THAT

IT'S GOING TO BE SO HARD TO FIND

THEM LATER IN LIFE.

AND ANOTHER WAY OF LOOKING AT IT

IS IF THERE WERE A WAY FOR THE

PATIENTS TO STAY INVOLVED AND TO

HAVE SOMEWHERE WRITTEN DOWN WHAT

STUDY THEY PARTICIPATED IN ON

WHAT DAY, WHAT THE IRB PROTOCOL

NUMBER WAS OR WHATEVER KIND OF

DATA THAT COULD TRAVEL THROUGH

THAT PATIENT'S LIFE WITH THEM

AND IT WERE IN THEIR HANDS TO BE

ABLE TO LOOK AT THAT STUDY AND

SEE WHERE IT'S AT AND HAVE THE

OPTION OF WITHDRAWING CONSENT

LATER IN LIFE.

ANOTHER WAY OF THINKING ABOUT IT

THAT AS WE, YOU KNOW, IN 2012 SO

WE CAN START THINKING ABOUT

DIFFERENT WAYS OF DOING THINGS.

SO MAYBE YOU COULD COMMENT ON

THAT.

>> SURE.

I THINK THAT'S AN EXCELLENT

POINT AND ANOTHER I THINK VERY

VALID WAY TO LOOK AT THIS DATA.

ANOTHER PART OF THE SURVEY I

DIDN'T REPORT THE DATA FROM

SUGGESTED THAT PEOPLE WERE IN

FACT, THAT'S WHAT THEY WERE

INTERESTED.

THEY WANTED TO KNOW THAT THEY

WERE PARTICIPATING IN RESEARCH

ESPECIALLY IF THEIR SAMPLES HAD

BEEN OFFERED IN A CLINICAL

CONTEXT AND NOT A RESEARCH

CONTEXT, THAT THAT NOTIFICATION

MIGHT BE A PERFECTLY ACCEPTABLE

WAY FOR THEM TO LEARN ABOUT IT.

IT OPENS THE DOOR IN OUR

THINKING TO MORE CREATIVE AND

NOVEL WAYS TO INFORM PEOPLE OF

WHAT WAS GOING ON WITHOUT

REQUIRING THE DOTTED LINE AND

THE SIGNATURE ON PAPER SO THAT

THIS OPENS THE DOOR FOR EXAMPLE

TO INTERNET DAYS, NEWS LETTERS

AND UPDATES THAT PEOPLE COULD GO

LOG IN.

OF COURSE THIS REQUIRES PEOPLE

TO HAVE ACCESS TO THOSE KINDS OF

TECHNOLOGIES AND SO WE WOULD

HAVE TO TAILOR THIS TO

PARTICULAR POPULATIONS.

BUT IF THERE ARE WAYS TO KEEP

PEOPLE APPRISED OF WHAT WAS

GOING ON, GIVING THEM CONTACT

INFORMATION SO THEY COULD PULL

THE PLUG IF THEY HAD ANY REAL

CONCERNS, BUT ARE THERE ARE

STEPS IN THE INTEREST OF KNOWING

WHAT'S BEING DONE WITH THEIR

CONTRIBUTION AND SORT OF

VALIDATING THEIR SENSE OF

WANTING TO FEEL ALTRUISTIC.

THIS IS SOMETIMES MORE RESOURCE

INTENSIVE APPROACHES BUT ONES

THAT PERHAPS ARE LESS RESOURCE

INTENSIVE THAN HAVING TO

RECONTACT AND GETTING

AFFIRMATIVE RECONSENT IN THIS

CASE FROM EACH PERSON AS THEY

TURN 18.

SO I THINK RESPECTING

INDIVIDUALS DOESN'T NECESSARILY

REQUIRE FORMAL INFORMED CONSENT,

IT REQUIRES THINGS LIKE MAKING

AN EFFORT AND MAKING THIS

INFORMATION AVAILABLE IN

DIFFERENT WAYS.

SO I THINK MORE RESEARCH ON

THOSE MECHANISMS IS ANOTHER AREA

THAT WOULD BE FRUITFUL FOR

EXPLORATION.

THANK YOU.

>> THANK YOU, SARA.

IT'S NOW MY PLEASURE TO

INTRODUCE MY COLLEAGUE, CAROL

WEIL WHO IS REGULATORY AFFAIRS

ADVISOR IN OUR OFFICE, THE

NATIONAL CANCER INSTITUTE OFFICE

OF RESPA TREE REPOSITORIES IN BIOSPECIMENS

RESEARCH.

SHE CAME TO OBGR IN JULY OF

2010.

SHE HAS A LAW DEGREE AND A

FELLOWSHIP IN MEDICAL ETHICS AND

SHE HAS SERVED U.S. DEPARTMENT

OF HEALTH AND HUMAN SERVICES

SINCE 1987.

FIRST WITH THE INSPECTOR

GENERAL'S OFFICE WHERE SHE

PROSECUTED MEDICARE AND MEDICAID

FRAUD AND ABUSE CASES FROM 1999

TO 2010.

WITH THE OFFICES FOR HUMAN

RESEARCH PROTECTION WHERE

SHEEHAN DULLED CLIMATE CASES AND

DEVELOPED PAUL TEASE EXPEJ

CASUAL GUIDANCE FOR

INSTITUTIONAL REVIEW BOARDS AND

CLINICAL INVESTIGATORS.

AND OUR OFFICE AT THE NCI SHE'S

WORKING TO RESOLVE AND IMPLEMENT

MULTIPLE ETHICAL LEGAL AND

SOCIAL ISSUES INVOLVED IN THE

ADMINISTERING THE REPOSITORIES

INCLUDING COLLECTION, STORAGE

AND FUTURE RESEARCH FEES.

AND SO CAROL IS GOING TO GIVE

THE FILM TALK TODAY WHICH IS

TITLED CONSENT FROM PEDIATRIC

BIOSPECIMENS DONORS AT THE AGE

OF MATURITY, A FRAMEWORK FOR

DECISION-MAKING.

CAROL.

>> THANK YOU FOR THAT

INTRODUCTION AND THANK YOU SARA

AND DAVE FOR YOUR VERY

INTERESTING PRESENTATIONS AND

THE DATA YOU HAVE COLLECTED.

BEFORE I BEGIN, I WOULD LIKE TO

ACKNOWLEDGE THE CONTRIBUTIONS

AND COLLABORATION OF MY

COLLEAGUES, SAMANTHA WARREN WHO

WAS A FELLOW IN BY USE

SUPPOSITORIES AND BIOSPECIMENS

AND NICOLE LOCKHART WHO IS IN

THE AUDIENCE TODAY AND HAS

CONTRIBUTED GREATLY IN THIS

PROJECT.

MY OBJECTIVES TODAY ARE TO FIRST

OF ALL DESCRIBE A

DECISION-MAKING FRAMEWORK THAT

WE HAVE DEVELOPED FOR

CONSIDERING THE MULTIPLE ETHICAL

CHALLENGES REGARDING WHETHER AND

WHEN TO ATTEMPT CONTACTING

FORMER PEDIATRIC BIOSPECIMEN

DONORS ONCE THEY HAVE REACHED

THE AGE OF MAJORITY IN ORDER TO

OBTAIN CONSENT FOR FUTURE USES

OF THEIR STORED BIOSPECIMENS.

AND SECONDLY TO DESCRIBE THE

MANY OPERATIONAL ISSUES THAT

RESEARCH BIOREPOSITORIES FACE

WHEN THEY ARE FORMULATING PAUL

TEASE AND PROCEDURES FOR

CONTACT -- POLICIES AND

PROCEDURES FOR CONTACTING

BIOSPECIMENS DONORS.

JUST TO BRIEFLY RUN THROUGH THE

REGULATORY CONSIDERATIONS SARA

AND DAVE HAVE DISCUSSED THESE

ALSO.

THE ISSUES SURROUNDING THE

COLLECTION OF SAMPLES FROM

CHILDREN IN TERMS OF THE

REGULATORY ASPECTS ARE CONTAINED

IN SUBPART D OF THE HUMAN

SUBJECT PROTECTION REGULATION,

THE PROVISIONS REQUIRING

PARENTAL PERMISSION, AND ALSO

THE ASSENT OF MINORS WHO ARE

DEEMED OLD ENOUGH AND MATURE

ENOUGH TO PROVIDE THAT ASSENT.

I THINK MOST IRBs USUALLY

CONSIDER AN APPROPRIATE AGE OF

CONSENT TO START AS EARLY AS 7.

I WAS VERY INTERESTED IN DAVE'S

VIEWS THAT THAT SEEMED QUITE

EARLY AND I HAVE TO SAY THAT I

AGREE, PARTICULARLY IN THE CASE

OF BIOSPECIMEN RESEARCH WHERE

THE ISSUES ARE NOT PHYSICAL OR

INTERVENTIONAL AND PRIMARILY

INVOLVE A LOT OF SUBJECTIVE

INFORMATIONAL CONCERNS THAT

CHILDREN AT YOUNG AGES REALLY

DON'T HAVE THE EXPERIENCE TO

WEIGH AND BALANCE.

SO I THINK THAT IN THE CONTEXT

OF BIOSPECIMEN RESEARCH, ASSENT

PERHAPS SHOULD BE CONSIDERED AT

AN OLDER AGE, MAYBE 10 OR 12 AS

DAVE ALSO SUGGESTED.

ONCE BIOSPECIMEN DONORS HAVE

REACHED THE AGE OF MAJORITY, THE

ISSUE OF WHETHER IT'S

APPROPRIATE TO SEEK TO CONTACT

THEM IN ORDER TO HAVE THEM WAIVE

INFORMED CONSENT FOR FUTURE USES

OF THOSE SPECIMENS IS AT

45CFR 46.116D.

THE REQUIREMENT FOR WAIVING

INFORMED CONSENT FROM FORMER

PEDIATRIC BIOSPECIMENS WOULD

FIRST OF ALL REQUIRE THAT THE

RESEARCH BE NO MORE THAN MINIMAL

RISK.

SECONDLY THAT THE WAIVER OF

INFORMED CONSENT WOULD NOT

ADVERSELY AFFECT THE RIGHTS

ORWELL FAIR OF THE SUBJECT.

AND FINALLY THAT THE RESEARCH

COULD NOT PRACTICALLABLY BE

CARRIED OUT WITHOUT THE WAIVER

OR THE INFORMED CONSENT.

IN TERMS OF THE QUESTION OF

MINIMAL RISK WHICH DAVE WENT

INTO IN SOME DETAIL.

AT THE POINT WHEN YOU HAVE

STORED BIOSPECIMENS, IN OTHER

WORDS THE COLLECTION HAS ALREADY

TAKEN PLACE AND THE SPECIMEN'S

BEEN STORED IN A BIOBANK, THE

RISKS ARE PRIMARILY THOSE OF THE

RELEASE OF THE INFORMATION AND

THE DATA THAT HAS BEEN STORED.

SO YOU WANT TO LOOK AT HOW

ROBUST THE DATA PROTECTION AND

DATA SECURITY PROVISIONS ARE IN

PLACE FOR A BIOREPOSITORY.

WHAT PLANS IF ANY ARE THERE IN A

PROPOSED RESEARCH PROJECT FOR

RELEASING DATA.

ARE WE TALKING ABOUT CONTROLLED

ACCESS, A LIMITED ACCESS OR

BROAD PUBLIC ACCESS.

AND ALSO WHAT PLANS ARE THERE

FOR RETURNING RESEARCH RESULTS.

TYPICALLY WE THINK OF RETURNING

RESEARCH RESULTS AS SOMETHING

THAT CAN PROVIDE BENEFITS TO

INDIVIDUAL PARTICIPANTS IN THE

RESEARCH, BUT THEY ALSO CAN

IMPOSE RISK, PARTICULARLY IF

THERE AREN'T PROVISIONS IN PLACE

FOR GENETIC COUNSELING OR OTHER

RESOURCES AVAILABLE TO

PARTICIPANTS IN ORDER TO FULLY

DISCUSS AND UNDERSTAND WHAT THE

RESULTS INVOLVE.

IN TERMS OF THE ISSUE OF WHETHER

THE WAIVER WOULD ADVERSELY

AFFECT THE RIGHTS AND WELFARE OF

SUBJECTS, WE WANT TO LEARN AS

MUCH AS WE CAN ABOUT WHAT A

PARTICULAR RESEARCH

PARTICIPANTS' PREFERENCES ARE IN

TERMS OF USE OF BIOSPECIMENS IN

FUTURE RESEARCH.

DO YOU HAVE A PARTICIPANTS WHO

HAS STRONG FEELINGS ABOUT

PRIVACY AND CONFIDENTIALITY.

WAS THIS A PARTICIPANT WITH A

RARE DISEASE FOR WHOM AS WE

HEARD PRIVACY AND

CONFIDENTIALITY OFTEN PALE IN

SIGNIFICANCE IN COMPARISON TO

THE OPPORTUNITY TO GAIN

KNOWLEDGE ABOUT ONE'S OWN

CONDITION, WHICH MIGHT ALSO

AFFECT OTHERS IN ONE'S FAMILY OR

MORE A ALTRUISTICALLY OTHERS OUT

IN THE PUBLIC.

DO WE HAVE ANY EVIDENCE OF

WHETHER CONTACT WOULD BE

APPRECIATED BY THE INDIVIDUAL

RESEARCH PARTICIPANTS OR WOULD

IT MORE LIKELY BOO BE INTRUSIVE.

LOOK AT THE CONTEXT OF WHICH THE

BIOSPECIMENS WERE COLLECTED.

DID THE RESEARCH PARTICIPANTS

HAVE A POTENTIALLY FRAITLE

DISEASE, A NEURO BLASTOMA WHERE

BY THE TIME THE SPECIMENS HAVE

BEEN STORED FOR SEVERAL YEARS,

THAT PERSON MAY BE DECEASED AND

CONTACT MAY INVOLVE REACHING

FAMILY MEMBERS WHO COULD STILL

BE GRIEVING.

THE FINAL ISSUE, WHETHER OR NOT

RESEARCH COULD PRACTICALLABLY BE

CARRIED OUT WITHOUT THE WAIVER

INVOLVES TWO CONCERNS.

FIRST THE LOGISTICAL ISSUE OF

WHETHER OR NOT THERE IS ADEQUATE

INFORMATION AVAILABLE TO CONTACT

THE INDIVIDUAL PARTICIPANT.

IS THERE AN EFFECTIVE TRACKING

MECHANISM THAT THE BIOREPOSITORY

OR INVESTIGATOR HAS KEPT IN

PLACE.

HOW MANY SUBJECTS ARE WE TALKING

ABOUT FOR A PARTICULAR STUDY.

IS THIS SOMETHING THAT THE

BIOREPOSITORY CAN HANDLE FINALLY

AND HAS PLANNED FOR IN ITS

RESEARCH PLAN.

THE SECOND ASPECT OF

PRACTICALLABILITY HAS TO DO WITH

WHETHER OR NOT THE SPECIMENS AT

ISSUE ARE NECESSARY IN ORDER FOR

THE STUDY TO BE EFFECTIVELY

CARRIED OUT.

ARE THESE SPECIMENS CRITICAL TO

THE DESIGN OF THE STUDY.

WITHOUT THEM, WILL THE STUDY BE

UNDER POWERED OR RESULTS BE

SKEWED.

SO THAT IT IS IMPRACTICALLABLE

FOR THE RESEARCH TO CONTINUE

WITHOUT SEEKING THESE SPECIMENS,

AN ARGUMENT THAT WOULD FAVOR

WAIVING INFORMED CON SENT.

THE OFFICE FOR HUMAN RESEARCH

PROTECTION HAS ISSUED A DOCUMENT

CALLED GUIDANCE ON CODING WHICH

FURTHER ELABORATES ON THESE

REGULATORY CRITERIA.

THE GUIDANCE BEGINS WITH A

DISCUSSION OF THE REGULATORY

DEFINITION OF HUMAN SUBJECTS.

THE HHS REGULATIONS DEFINE HUMAN

SUBJECTS AS A LIVING INDIVIDUAL

ABOUT WHOM AN INVESTIGATOR

OBTAINS EITHER DATA THROUGH

INTERVENTION OR INTERACTION.

FOR EXAMPLE THE COLLECTING

INVESTIGATOR WHO IS OBTAINING

THE SAMPLES THROUGH AN IMMEDIATE

CONTACT WITH THE RESEARCH

PARTICIPANTS.

OR OBTAINING IDENTIFIABLE

PRIVATE INFORMATION.

IF THE INVESTIGATOR IS RECEIVING

SPECIMENS THROUGH A MECHANISM

SUCH AS A MATERIAL TRANSFER

AGREEMENT, IT'S HIGHLY LIKELY

THAT THE INFORMATION BEING

OBTAINED IS NOT READILY

ASCERTAINABLE AND THAT THE

SPECIMENS ARE CODED OR

TRANSFERRED IN SOME FORM THAT

THE INVESTIGATOR DOWN STREAM

WILL NOT BE ABLE TO IDENTIFY THE

INDIVIDUALS INVOLVED.

SO THE OHRP GUIDANCE ON CODING

ESSENTIALLY SAYS THAT

INFORMATION -- EXCUSE ME

RESEARCH INVOLVING CODED PRIVATE

INFORMATION OR SPECIMEN IS NOT

RESEARCH INVOLVING A HUMAN

SUBJECT.

IF THE INFORMATION OR SPECIMENS

INVOLVED ARE NOT BEING COLLECTED

FOR ANY CURRENTLY PROPOSED

RESEARCH PURPOSE, THAT WOULD BE

THE COLLECTING INVESTIGATOR

SCENARIO FROM BEFORE.

AND THE CODING SYSTEM IS SUCH

THAT INVESTIGATORS CAN'T READILY

ASCERTAIN THE IDENTITY OF THE

INDIVIDUALS WHO WERE LINKED TO

THE CODED SAMPLES.

SO IN ORDER TO USE THE FRAMEWORK

THAT I'M GOING TO PROPOSE HERE

FOR DETERMINING WHEN IT'S

APPROPRIATE TO ATTEMPT TO

CONTACT FORM TE FORMER PEDIATRIC

BIOSPECIMEN DONORS.

WE WANT TO LOOK AT REGULATORY

ISSUES AND RULE OUT THAT CONSENT

IS REGULA REGULATORILY MANDATED.

YOU HAVE ONGOING STUDY WITH

INTERVENTION OR INTERACTION WITH

SUBJECTS.

BECAUSE IF YOU DO, THEN THAT

STUDY IS GOING TO INVOLVE HUMAN

SUBJECTS RESEARCH.

YOU'RE NOT GOING TO BE ABLE TO

WAIVE CONSENT IF YOU HAVE

PERIODIC RECONTACT WITH THE

PARTICIPANTS AND CONSENT WILL BE

REQUIRED.

BUT IF YOU DON'T HAVE AN ONGOING

STUDY THEN THE NEXT QUESTION YOU

WOULD ASK IS UNDER THAT SECOND

PROJECT OF THPRONG OF THE DEFINITION OF TH
E

HUMAN SUBJECT IS THE IDENTITY OF

THE DONOR READILY ASCERTAINABLE.

AND IF IT IS, YOU WANT TO FIND

OUT WHAT KIND OF PATIENT

POPULATION YOU'RE LOOKING AT.

DO YOU HAVE A BIOSPECIMEN DONOR

OR GROUP OF DONORS WHO ARE

DECEASED, BECAUSE IF YOU KNOW

FOR A FACT THAT THE DONORS ARE

DECEASED, THEN CONSENT IS NOT

GOING TO BE POSSIBLE UNLESS YOU

HAVE SUBHUMAN MOWERS AND YOU CAN

CONTACT PEOPLE FROM BEYOND --

POWERS AND YOU CAN CONTACT

PEOPLE FROM BEYOND BECAUSE YOU

WILL NOT BE ABLE TO REACH THOSE

DONORS IF THEY ARE DECEASED.

IF YOU DON'T KNOW THE DONORS ARE

DECEASED THEN THAT'S AN OCCASION

WHEN YOU CAN USE OUR FRAMEWORK.

IF THE IDENTIFIABLITY OF THE

DONOR IS NOT READILY

ASCERTAINABLE, THEN YOU WOULD

ASK WHETHER OR NOT THE SPECIMENS

ARE CODED.

AND IF THEY'RE NOT CODED, HAVE

IDENTIFIERS BEEN STRIPPED SUCH

THAT THE SPECIMENS ARE

ANONYMIZED.

IF THEY ARE ANONYMIZE THE, ONCE

AGAIN CONSENT IS NOT GOING TO BE

POSSIBLE BUT YOU'RE NOT DEALING

WITH HUMAN SUBJECT RESEARCH

BECAUSE YOU DON'T HAVE SAMPLES

THAT ARE READILY ASCERTAINABLE

TO THE INVESTIGATORS.

NOW, IN THIS CATEGORY HERE,

THERE, WHERE CONSENT IS NOT

POSSIBLE BUT YOU'RE DEALING NOT

WITH HUMAN SUBJECTS RESEARCH.

THIS DOES ADDRESS THE ISSUE OF

WHETHER YOU CAN ATTAIN CONSENT

BUT IT DOESN'T SPEAK TO THE

UNDERLYING ETHICAL ISSUE OF

WHETHER IT'S APPROPRIATE TO USE

THOSE SAMPLES IN RESEARCH.

AND I WOULD ARGUE THAT IT'S NOT

ETHICALLY APPROPRIATE TO USE

SAMPLES ANY TIME YOU HAD A

CONSENT THAT WAS NARROWLY

TAILORED AND THE CURRENT

RESEARCH PURPOSE OR PROPOSED

RESEARCH PURPOSE GOES BEYOND

THAT CONSENT.

SO TO FURTHER THE FLOW CHART

HERE, IF SAMPLES AND DATA ARE

CODED OR IF NOT CODED, NOT

ANONYMIZED OR IF YOU'RE DEALING

WITH BIOSPECIMEN DONORS WHO ARE

READILY ASCERTAINABLE BUT NOT

DECEASED, THAT IS WHEN YOU WOULD

GO AHEAD AND USE OUR FRAMEWORK.

THE ETHICAL CONSIDERATIONS THAT

PERTAIN IN THE FRAMEWORK ARE

FIRST AND PRIMARILY WHAT THE

POTENTIAL HARM MIGHT BE TO THE

DONOR OR THE DONOR'S FAMILY.

WOULD CONTACT BE SOMETHING THAT

WOULD BE WANTED BY THE DONOR.

IS THIS SOMEONE FOR WHOM

AUTONOMY HAD GREAT PRECEDENCE OR

IS IT MORE LIKELY THAT THE DONOR

WILL BE DECEASED AND YOU'RE

GOING TO BE CONTACTING A

GRIEVING FAMILY.

WHAT ABOUT THE COMMUNITY

PERSPECTIVE.

IS THIS A RESEARCH PARTICIPANT

WHO WAS PART OF A DISEASE

ORACLURAL COMMUNITY THAT WAS

HIGHLY ENGAGED IN THE RESEARCH

SUCH AS THE HIV COMMUNITY WAS IN

THE 1980'S AND IS THAT A

PERSPECTIVE YOU WANT TO TAKE

INTO ACCOUNT BEFORE DECIDING

WHETHER OR NOT IT'S APPROPRIATE

TO SEEK CONSEPTEMBE CONSENT OR WAIVE

CONSENT.

WHAT IS THE NATURE OF

CONTEMPLATED ACTIVITY YOU ARE

LOOKING AT AT THE POINT THE

BIOSPECIMEN DONOR EVANS OF

REACHES OF THE AGE OF MATURITY.

ARE YOU LOOKING FOR THE

REPOSITORY OR IS THERE IN FACT A

PROPOSED USE.

THE SECRETARY'S ADVISORY

COMMISSION ON HUGE SUBJECT

PROTECTION HAS TAKEN A POSITION

ON THE FORMER ISSUE THAT OF

STORAGE AND SAID THAT CONTINUED

STORAGE OF PEDIATRIC

BIOSPECIMENS ONCE THE DONOR'S

REACHED THE AGE OF MAJORITY

SHOULD NOT BE CONSIDERED AN

OCCASION REQUIRING CONSENT FROM

THOSE NOW ADULT DONORS.

THERE ARE NOT ENOUGH RISKS

CONTINUED WITH ASSOCIATED

STORAGE TO WARRANT THAT KIND OF

INTERVENTION AT THAT POINT.

WHAT ABOUT THE DEGREE OF DATA

SHARING PROPOSED.

ARE WE TALKING ABOUT LIMITED OR

BROAD ACCESS TO DATA.

AND FINALLY WHAT IS THE NATURE

OF ANY PROPOSED RESEARCH

PROJECT.

IS THIS SOMETHING THAT'S HIGH

RISK THAT THERE ARE A LOT OF

GENETIC INFORMATION THAT COULD

BE RELEASED OR ARE WE TALKING

ABOUT SOMETHING CONTROVERSIAL

FOR WHICH THERE IS NOT GREAT

PUBLIC AGREEMENT, STEM CELL

RESEARCH OR RESEARCH INTO

REPRODUCTIVE TECHNOLOGY WHERE

THERE ARE LARGE POSURES OF THE

POPULATION THAT DON'T SUPPORT

THAT -- PORTIONS OF THE

POPULATION THAT DON'T SUPPORT

THAT.

THERE'S A KEY THAT CAN BE

APPLIED TO A LIST OF

CONSIDERATIONS THAT WILL HELP TO

INFORM WHETHER OR NOT IT'S

APPROPRIATE TO AS AN ETHICAL

MATTER SEEK CONSENT FROM FORMER

PEDIATRIC BIOSPECIMEN DONORS.

AND WE USE A STOP LIGHT BECAUSE

FOR EACH CONSIDERATION THAT WE

TAKE INTO ACCOUNT, WE REACH A

CONCLUSION AND DRAW A CONCLUSION

THAT WILL EITHER ALLOW THE

RESEARCH TO GO FORWARD WITHOUT

CONSENT, A GREEN LIGHT MEANING

GO FORWARD OR THE ISSUE IS NOT

ETHICALLY DEPOSITIVE MEANING BE

CAUTIOUS, LOOK FURTHER AND LOOK

FOR OTHER CONSIDERATIONS.

A RED LIGHT CLASSIFICATION FOR

THOSE INFORMATION WHERE ONE

SHOULDN'T GO FORWARD WITH THE

RESEARCH, ONE SHOULD STOP AND

STRONGLY CONSIDER OBTAINING

CONSENT.

HERE WE'LL USE PURPLE FOR YELLOW

BECAUSE IT'S ACTUALLY QUITE HARD

TO SEE YELLOW ON THE SLIDE.

SO IN USING THE FRAMEWORK, THERE

ARE THREE BROAD CATEGORIES OF

CONSIDERATIONS THAT NEED TO BE

TAKEN INTO ACCOUNT.

AND FOR EACH OF THOSE

CATEGORIES, WE APPLY THE STOP

LIGHT KEY TO DRAW A PRELIMINARY

CONCLUSION ABOUT WHETHER CONSENT

IS ETHICALLY APPROPRIATE IN THAT

PARTICULAR CIRCUMSTANCE.

THE THREE CATEGORIES ARE HARM TO

DONORS OR TO DONOR FAMILIES.

RESEARCH PURPOSE OR THE NATURE

OF THE RESEARCH AND FINALLY

FEASIBILITY.

ONCE AGAIN, A GREEN

CLASSIFICATION MEANS THE

RESEARCH MAY PERCEIVE WITHOUT

CONSENT.

A YELLOW CLASSIFICATION BE

CAUTIOUS, CONSENT IS POSSIBLY

ETHICALLY APPROPRIATE OR

MANDATED AND A RED

CLASSIFICATION STOP AND SEEK

CONSENT, CONSENT IS ETHICALLY

MANDATED BEFORE PROCEEDING WITH

THE RESEARCH.

THE FIRST CATEGORY POTENTIAL

HARM TO DONOR OR DONORS FAMILY

CAN BE DIVIDED INTO TWO

SUBCATEGORIES.

THE FIRST, THE PSYCHOLOGICAL

IMPACT OF CONTACT ON THE DONOR

OR THE DONOR'S FAMILY AND THE

SECOND, THE IMPACT OF THE STUDY

ITSELF OR THE RESEARCH ACTIVITY

ON THE DONOR OR DONOR'S FAMILY.

IF YOU HAVE A SITUATION WHERE

YOU KNOW OR HAVE STRONG

SUSPICIONS THAT CONTACT WOULD BE

UNDESIRED, PERHAPS FROM THE

ASSENT DOCUMENT THAT WAS

OBTAINED FROM THE PEDIATRIC

DONOR HIS OR HERSELF OR FROM

APARTMENT DOATLE CIRCUMSTANCES

CIRCUMSTANCES -- ANECDOTAL

CIRCUMSTANCES THAT YOU'RE AWARE

OF, THAT WOULD ARGUE FOR A

CLASSIFICATION OF GRAIN.

PROCEED WITH THE RE-- GREEN,

PROCEED WITH THE RESEARCH FOR

CONSENT SOMETHING THAT'S

ETHICALLY MANDATED.

IF YOU REASON TO BELIEVE THAT

THE PEDIATRIC BIOSPECIMEN DONOR

IS NO LONGER ALIVE, YOU WOULD

NOT OBTAIN YOUR GOAL OF BEING

ABLE TO OBTAIN CONSENT BUT WOULD

ONLY BE CONTACTING POTENTIALLY

TRAUMATIZING THE DONOR'S FAMILY.

ONCE AGAIN IT WOULD BE

APPROPRIATE TO DRAW A CONCLUSION

OF ASSIGNING THE GREEN

CLASSIFICATION THAT CONSENT

WOULD NOT BE NECESSARY AND THAT

THE RESEARCH MAY PROCEED.

IF YOU DON'T HAVE ENOUGH FACTS

ABOUT THE DONOR OR THE DONOR'S

FAMILY IN TELLERS OF WHA TERMS OF WHAT THE
Y

WOULD HAVE WANTED FOR BEING

RECONTACTED, OR IF THERE ARE

KNOWN CONFLICTS AMONG SURVIVING

FAMILY MEMBERS, THEN YOU WOULD

WANT TO DESIGNATED THIS A YELLOW

CLASSIFICATION, PROCEED WITH

CAUTION.

AND FINALLY IF YOU KNOW THAT

THIS IS A INDIVIDUAL WHO HIGHLY

PRIZE THEIR AUTONOMY, THEIR

ABILITY TO BE ABLE TO CONSENT

WHO PROCEDURES OF THIS SORT,

THEN YOU WOULD WANT TO HALT THE

RESEARCH AND REQUIRE CONSENT

FROM THAT RESEARCH PARTICIPANT.

IN TERMS OF THE SECOND

SUBCATEGORY, THE IMPACT OF THE

STUDY OR THE ACTIVITY ON THE

DONOR OR THE DONOR'S FAMILY.

HERE WE'RE LOOKING TO THE NATURE

OF THE PROPOSED ACTIVITY ITSELF.

ARE WE TALKING ABOUT A LOW RISK

OR NONSENSITIVE TYPE OF RESEARCH

ACTIVITY.

PERHAPS THE COLLECTION OF

BIOSPECIMENS IN ORDER TO TEST

SUSTAINING TECHNIQUE OR TO TRAIN

PATHOLOGISTS.

SOMETHING THAT WOULDN'T PRODUCE

ANY DISCRIMINATING OR SENSITIVE

CONTROVERSIAL INFORMATION VERSUS

SOMETHING WITH A MEDIUM RISK,

THE GENETIC VARIANCE OF A COMMON

DISEASE, FOR EXAMPLE.

VERSUS SOMETHING THAT IS HIGH

RISK AND CONTROVERSIAL.

ARE WE GOING TO BE DEVELOPING

RESEARCH RESULTS THAT INVOLVE A

DISEASE-LIKE SCHIZOPHRENIA OR

DEPRESSION OR DOES THAT INVOLVE

RESEARCH THAT IS POTENTIALLY

CONTROVERSIAL SUCH AS STEM CELL

RESEARCH.

IN THOSE CASES, YOU WOULD

APPROPRIATELY DESIGNATE THE

CORRECT COLOR CLASSIFICATION

BASED ON THE TYPE OF RESEARCH

ACTIVITY THAT IS BEING

CONSIDERED.

THE NEXT CATEGORY OF

CONSIDERATIONS INVOLVE THE

CHARACTERISTICS OF THE RESEARCH

ACTIVITY ITSELF.

AND THIS CAN BE FURTHER DIVIDED

INTO TWO SUBCATEGORIES, THE

CONTEMPLATED ACTIVITY AT ISSUE

VERSUS THE DEGREE OF DATA

SHARING.

IN TERMS OF THE CONTEMPLATED

ACTIVITY, ARE WE TALKING ABOUT A

KNOWN USE OR A SET OF USES THAT

ARE PLANNED OR A POSSIBLE FUTURE

USE OR MERE CONTINUATION OF

STORAGE AT THE POINT IN TIME

WHEN THE PEDIATRIC DONOR REACHES

THE AGE OF MAJORITY.

IF WE'RE ONLY TALKING ABOUT

CONTINUED STORAGE, THEN YOU

WOULD DESIGNATE THIS CATEGORY A

GREEN LIGHT TO PROCEED WITH THE

RESEARCH, CONSENT SHOULD NOT BE

ETHICALLY MANDATED.

IF YOU HAVE A CURRENT OR KNOWN

USE, SOMETHING ABOUT WHICH YOU

COULD EASILY CONTACT SOMEBODY,

THEN YOU WOULD DESIGNATE THIS A

RED OR DO NOT PROCEED WITH THE

RESEARCH WITHOUT FIRST

CONSIDERING CONSENT.

IN TERMS OF THE DEGREE OF DATA

SHARING, THE MORE LIMITED YOUR

PROPOSED DATA SHARING PLAN IS,

FOR EXAMPLE WITHIN THE RESEARCH

TEEN ONLY, THE MORE LIKELY YOU

WILL DESIGNATE THIS A GREEN FOR

GO AHEAD WITH THE RESEARCH.

IF YOU HAVE A MIDDLE LEVEL OF

RESEARCH, OF DATA ACCESSIBILITY,

CONTROLLED ACCESS, THEN

SOMETHING LIKE THE DB BEGAN DATA

BASE AT NIH THEN THAT WOULD GET

A YELLOW LIGHT.

IF YOU'RE TALKING ABOUT FULL

BLOWN PUBLIC ACCESS THAT WOULD

PROBABLY GET A RED

CLASSIFICATION FOR THIS

CATEGORY.

THE THIRD CATEGORY INVOLVES THE

FEASIBILITY OF CONTACTING THE

FORMER PEDIATRIC BIOSPECIMEN

DONOR AND ALSO THE FEASIBILITY

OF CONDUCTING THE RESEARCH

WITHOUT THE SAMPLES AT ISSUE.

SO IN TERMS OF THE AVAILABILITY

OF CONTACT INFORMATION, IF THE

BIOREPOSITORY HAS NOT MAINTAINED

CONTACT INFORMATION OR IF THE

SPECIMENS WERE COLLECTED SO LONG

AGO THAT INFORMATION IS LIKELY

TO BE INACCURATE, YOU WOULD GIVE

THIS CONSIDERATION A GREEN

LIGHT.

GO FORWARD WITH THE RESEARCH,

CONTACT IS NOT LIKELY TO YIELD A

RELEVANT CONSENT INFORMATION.

IF THE ACCURACY AND AVAILABILITY

OF CONTACT INFORMATION IS

UNKNOWN, THEN THIS ISSUE IS NOT

GOING TO BE DISPOSITIVE AS AN

ETHICAL MATTER SO YOU WOULD GIVE

THIS CATEGORY A YELLOW LIGHT.

IF THE CONTACT INFORMATION IS

KNOWN AND ACCURATE SUCH THAT IT

WOULD BE RELATIVELY EASY TO

REACH THE INDIVIDUAL INVOLVED,

YOU KNOW THAT THE INDIVIDUAL IS

LIKELY TO STILL BE ALIVE, THEN

YOU WOULD GIVE THIS CATEGORY ON

RED LIGHT.

DO NOT PROCEED WITH THE RESEARCH

UNTIL YOU SEEK CONSENT.

IN TERMS OF THE EFFECT ON

SCIENTIFIC VALIDITY, IF THE

SAMPLE IS CRITICAL TO THE

RESEARCH AT ISSUE, PERHAPS

YOU'RE DEALING WITH RARE DISEASE

RESEARCH OR THE NATURE OF THE

STUDY DESIGN IS SUCH THAT THE

SAMPLE IS CRITICAL TO THE END

RESULT, THEN YOU WOULD GIVE THIS

A RED LIGHT.

I'M SORRY, YOU WOULD GIVE THIS A

GREEN LIGHT.

THE SAMPLE IS NEEDED TO YIELD A

SCIENTIFICALLY, TO YIELD

SCIENTIFICALLY VALIDAT VALID RESEARCH.

IF THE IMPACT OF SCIENTIFIC

VALIDITY IS UNKNOWN, THIS WOULD

GET A YELLOW LIGHT.

AND IF RESEARCH WILL NOT BE

NEGATIVELY IMPACTED BY LOST USE

OF THE SAMPLE, THEN THIS WOULD

GET A RED LIGHT.

SO, IN ORDER TO USE THIS

FRAMEWORK AND TO ANALYZE ALL OF

THE ETHICAL CONCERNS INVOLVED,

YOU WOULD USE THE STOP LIGHT KEY

TO WEIGH EACH OF THE BROAD THREE

CATEGORIES AND THE SUBCATEGORIES

OF CONSIDERATION.

AND THEN IN MOST SITUATIONS

RECEIVE A MIX OF DIFFERENT COLOR

CLASSIFICATIONS.

SO IMPORTANTLY, THIS ISN'T AN

ALGORITHM WHERE YOU PUT IN A LOT

OF CONSIDERATIONS AND PUNCH A

BUTTON AND GET OUT OF THE BLACK

BOX AND ANSWER TO WHETHER OR NOT

IT'S APPROPRIATE TO SEEK

CONSENT.

THE FRAMEWORK IS REALLY DESIGNED

AS A TOOL TO ASSIST DECISION

MAKERS BY REPAWS TREES REPOSITORIES, IRBs

AND RESEARCH INVESTIGATORS WHAT

TO DO WHEN THEY HAVE STORED

PEDIATRIC BIOSPECIMENS AND ARE

STORING THEM FOR LONG PERIODS OF

TIME AND THE BIOSPECIMENS HAVE

QUOTE/UNQUOTE GROWN UP.

IN ALL SITUATIONS, THE GREATEST

WAY WE FEEL SHOULD BE GIVEN TO

CATEGORY ONE, THE IMPACT OF THE

OF SEEKING CONSENT ON THE DONOR

OR THE DONOR'S FAMILY BECAUSE

THAT IS THE CATEGORY THAT

INVOLVES THE MOST CRITICAL

ISSUES IN TERMS OF PATIENT

PROTECTION AND HUMAN SUBJECT

PROTECTION.

NOW TURNING FROM THE FRAMEWORK

TO A CONSIDERATION OF ISSUES OF

BY I DON'T BANK IMPLEMENTATION,

WE BELIEVE THAT BIOREPOSITORIES

THAT ARE COLLECTING PEDIATRIC

SAMPLES NEED TO IMPLEMENT

POLICIES AND PROCEDURES AND

THINK THROUGH IN THE PLANNING

STAGES OF THE BIOREPOSITORY THE

TYPES OF OPERATIONAL GUIDELINES

THAT SHOULD BE IMPLEMENTED WHEN

DEALING WITH THE COLLECTION AND

STORAGE OF PEDIATRIC SPECIMENS.

THESE INCLUDE HOW WILL CONSENT

AT THE AGE OF MAJORITY BE

HANDLED IN THE CONSENT, IN THE

PARENTAL PERMISSION AND THE

ASSENT DOCUMENTS AT THE TIME OF

COLLECTION.

SO IN OTHER WORDS, WILL YOU PA

PARTURE LATE -- AND GET CONSENT

AND EVEN AS DAVE ALLUDED A YOUNG

CHILD NOT CAPABLE OF ASSENT BUT

AT LEAST YOU COULD GIVE

INFORMATION TO THAT INDIVIDUAL

AT A LATER POINT IN LIFE YOU

WOULD BE LED TO BELIEVE THAT

PERSON MIGHT BE ABLE TO DEVELOP

AN OPINION ABOUT WHETHER OR NOT

THEIR SAMPLE SHOULD BE USED IN

RESEARCH.

HOW WILL THE AGE OF MAJORITY BE

DEFINED.

WILL YOU LOOK TO WHAT THE AGE OF

MAJORITY IS IN THE JURISDICTION

WHERE THE BIOREPOSITORY IS

LOCATED.

WHAT IF THE PARTICIPANT HAS

MOVED.

YOU LOOK TO THE AGE OF THE STATE

WHERE THAT INDIVIDUAL NOW

RESIDES.

THERE ISN'T A LEGAL ANSWER TO

THIS AND SO AT THIS POINT IN

TIME IT'S REALLY AN ISSUE OF

PAULITY IPOLICY IN TERMS OF HOW

BIOREPOSITORIES CHOOSE TO

ADDRESS THE ISSUE.

HOW AND BY WHOM WILL DONOR

CONTACT BE OBTAINED -- BE

MAINTAINED.

WILL INFORMATION BE KEPT AT THE

COLLECTING INSTITUTION.

IF THAT IS DIFFERENT FROM THE

BIOREPOSITORY WHERE THE

INFORMATION IS STORED, WILL THE

BY I DON'T REPOSITORY ITSELF

KEEP THE CONTACT INFORMATION.

AND WILL THERE BE A FUNNEL

BETWEEN THE TWO INSTITUTIONS TO

MAKE SURE THE CONTACT

INFORMATION IS KEPT ACCURATE.

HOW WILL DONORS BE CONTACTED.

WILL THERE BE A LETTER SENT TO

THEM, WILL THEY BE TELEPHONED,

WILL YOU USE SOME COMBINATION OF

BOTH.

WHO WILL CONTACT THE DONOR.

WHAT STAFF ARE WE TALKING ABOUT.

HOW LONG WILL BE SPENT SEEKING

CONSENT AND WHAT METHODS WILL BE

USED TO OBTAIN CONTENT.

WHAT IS IT LONG ENOUGH TO HAVE

TRIED AND WHEN IS IT APPROPRIATE

TO CEASE EFFORTS.

AND WHAT WILL HAPPEN IF THE

DONOR CANNOT BE CONTACTED OR

DOESN'T RESPOND TO REPEATED

ATTEMPTS TO CONTACT.

WHAT WILL HAPPEN TO SPECIMENS

AND DATA IN THE BIOBANK IF THE

DONOR REFUSES CONSENT.

ARE THEY DESTROYED, ARE THEY

RETURNED.

WHAT WILL HAPPEN TO SPECIMENS IN

DATA THAT HAVE ALREADY BEEN

DISTRIBUTED TO DONORS IF AT THAT

POINT IN TIME A DONOR REFUSES

CONSENT.

NOW THE OFFICE FOR HUMAN

RESEARCH PROTECTION HAS A

DOCUMENT AND GUIDANCE ON THE

WITHDRAWAL OF CONSENT THAT

ARGUABLY IS ANALOGOUS TO THIS

SITUATION.

BUT THAT DOWN WASN'T INTENDED TO

APPLY TO PEDIATRIC BIOSPECIMENS

THAT ARE COLLECTED AT A POINT

PRIOR TO CONSENT WHEN THERE'S

ONLY PARENTAL PERMISSION AND

POTENTIALLY THE ASSENT OF THE

CHILD.

SO IT'S NOT ENTIRELY CLEAR THAT

THAT OHRP WILL CONSIDER THAT

GUIDANCE APPLICABLE BUT IT'S

PROBABLY THE MOST RELEVANT

GUIDANCE OUT THERE ON HOW TO

HANDLE THE SITUATION.

HOW WILL THE BIOBANK HANDLE A

DONOR REQUEST FOR THE RETURN OF

HIS OR HER SPECIMENS.

IS THAT EVEN SOMETHING THAT

STATE AND LOCAL LAWS WILL PERMIT

IN TERMS OF THE BIOHAZARD ISSUES

INVOLVED.

HOW WILL THE BIOBANK ENGAGE THE

AFFECTED COMMUNITY ON RECONTACT

ISSUES.

ONE CONCLUSION THAT'S EASY TO

DRAW FROM THE PRESENTATIONS OF

DAVE, SAY SA SARA AND MYSELF IS THERE'S

SERIOUS NEED FOR FURTHER

EMPIRICAL RESEARCH ON THE ISSUE

WHEN IS IT APPROPRIATE TO SEEK

TO RECONTACT FORMER BIOSPECIMENS

DONORS AND WHEN THAT KIND OF

CONTACT IS ETHICALLY RESPECTFUL.

IT WAS VERY INTERESTING TO ME

THAT SARA POINTED OUT HER DATA

HAD BEEN CITED BY TWO SEPARATE

AUTHORS FOR TWO CONFLICTING

CONCLUSIONS.

BECAUSE I THINK THERE'S A LOT OF

QUESTION AND CONCERN OUT THERE

ABOUT HOW TO NOT ONLY UNDERSTAND

WHAT PARTICIPANTS FEEL BUT HOW

TO INTERPRET WHAT WE'RE HEARING

FROM THEM.

THE FRAMEWORK THAT I PRESENTED

TODAY IS DESIGNED AS A TOOL TO

ASSIST INVESTIGATORS IRBs AND

BIOBANKS AND IMPORTANTLY IS NOT

TO SUBSTITUTE FOR THEIR

JUDGMENT.

BUT IT'S A TOOL TO USE IN THE

ABSENCE OF WHAT'S CRITICALLY

NEEDED, BETTER DATA ON HOW BEST

TO PROTECT PARTICIPANT

PREFERENCES.

I THINK AS A FIRST STEP, WE

REALLY NEED TO CONSIDER SERVING

GROWN PEDIATRIC BIOSPECIMEN

DONORS THEMSELVES TO LEARN WHAT

THEY THINK.

THERE HAVE BEEN AN AWFUL LOT OF

SURVEYS AND RESEARCH DONE ON

WHAT PARENTS FEEL OR WHAT EVEN

CHILDREN FEEL BUT NO WORK THAT

I'VE SEEN ACTUALLY LOOKING AT

FORMER PEDIATRIC BIOSPECIMEN

DONORS THEMSELVES.

SO I THINK AS A NEXT STEP, THAT

WOULD BE A VERY CRITICAL AREA OF

INQUIRY.

AND THAT'S IT.

I WILL TAKE A FEW QUESTIONS NOW

AND THEN CALL SARA AND DAVE UP

IN CASE THERE ARE ADDITIONAL

QUESTIONS FOR THE THREE OF US.

[APPLAUSE]

SNOW BUT WE ARE WORKING ON THAT.

WE'RE JUST FINISHING UP THE

PAPER, ACTUALLY.

YES.

>> SO THE QUESTIONER SAID THAT

THE FRAMEWORK SEEMED FOCUSED ON

LOOKING AT INDIVIDUAL RESEARCH

PARTICIPANTS AND MAYBE WHAT

THEIR PRERNSES OR CONCERNS ARE

IN TERMS OF THE RESEARCH

CONDUCTED AT NIH THAT IT'S OFTEN

THE CASE THAT ONE WOULD NOT

NECESSARILY KNOW WHAT THE VIEWS

OF INDIVIDUAL RESEARCH

PARTICIPANTS MIGHT BE.

AND I THINK THAT'S A VERY VALID

POINT.

WHAT AR OUR FRAMEWORK TRIES TO TAKE

INTO ACCOUNT IS NOT JUST THE

SPECIFIC AND THE KNOWN

PREFERENCES OF INDIVIDUALS BUT

ALSO BROAD CATEGORIES.

FOR EXAMPLE, IF YOU'RE DEALING

WITH THE NEURO BLASTOMA

POPULATION, IT'S QUITE LIKELY

THAT WHEN YOU'RE TALKING ABOUT

CONSENT AT THE AGE OF MAJORITY,

A NUMBER OF THOSE INDIVIDUALS

WILL BE DECEASED.

WHEN YOU'RE CONTEMPLATING

RECONTACT, YOU'RE REALLY TALKING

ABOUT CONTACTING FAMILY AND NOT

DONORS.

SO ONE THING TO LOOK AT IS THE

NATURE, NOT JUST WHAT YOU

ABSOLUTELY KNOW ABOUT

INDIVIDUALS BUT THE NATURE OF

THE POPULATIONS YOU'RE LOOKING

AT AND IF YOU CAN DRAW

CONCLUSIONS MORE BROADLY ABOUT

THE POPULATION YOU CAN STILL

APPLY THE FRAMEWORK TO HELP YOU

GUIDE YOUR CONCLUSIONS.

ANYBODY ELSE?

ANY OTHER QUESTIONS FOR DAVE OR

SARA?

IF I CAN REPEAT THE QUESTION I

THINK SO MUCH CONCERN OF

RESEARCH TODAY INVOLVES GENETIC

AND GENOMIC ISSUES AND LARGE

COLLECTION OF DATA FROM CHILDREN

THAT COULD POTENTIALLY BE STORED

FOR LONG PERIODS OF TIME AND

INVOLVE RELEASE OF INFORMATION

INTO THE PUBLIC DOMAIN THAT

COULD HAVE IMPLICATIONS FOR

THOSE CHILDREN AND THEIR

FAMILIES FOR A LONG TIME TO

COME.

AND HOW DOES THAT IMPACT WITH

ANALYSIS.

I THINK THAT'S UNDOUBTEDLY TRUE

THAT WE'RE CERTAINLY EVOLVING IN

THE MEDICAL RESEARCH WORLD INTO

AN AREA WHERE ALMOST ALL FRUIT

FULL RESEARCH ENDEAVORS TODAY

INVOLVE HUGE COLLECTIONS OF

DATA.

AND INFORMATION THAT MIGHT BE

POTENTIALLY BENEFICIAL TO

RESEARCH PARTICIPANTS DOWN THE

LINE IN TERMS OF THE RETURN OF

RESULTS BUT ALSO COULD BE QUITE

PREJUDICIAL.

AND I THINK THAT WHAT WE NEED TO

DO MOSTLY IS HAVE A MORE ENGAGED

COMMUNITY THAT CAN WEIGH IN ON

THE VIEWS OF THE PUBLIC ABOUT

WHAT THE BALANCE, APPROPRIATE

BALANCE IS IN TERMS OF

PROTECTING PRIVACY AND SECURING

DATA, BUT AT THE SAME TIME

ACKNOWLEDGING THAT THE ABILITY

TO ACCESS THAT DATA BY MEDICAL

RESEARCHERS IS WHAT MOVES

SCIENCE FORWARD.

AND SO I THINK THE MORE THAT WE

ENGAGE THE COMMUNITY AS PARTNERS

IN THE RESEARCH PROCESS, THE

MORE TRANSPARENT WE ARE ABOUT

INCLUDING THEM IN DECISIONS

ABOUT WHETHER WE'RE GOING TO BE

RECONTACTING OR WHETHER WE'RE

GOING TO BE USING TISHED TISSUES FOR

SPECIFIC PURPOSES.

THE MORE LIKELY WE ARE TO GO

FORWARD WITH POLICIES THAT ARE

CONSIDERED ACCEPTABLE.

AND I THINK THAT ALSO GETS TO

THE INTEGRAL CONUNDRUM THAT SARA

TOLD US ABOUT HER RESEARCH BEING

INTERPRETED IN DIFFERENT WAYS BY

DIFFERENT PEOPLE.

AND ALSO THAT INDIVIDUALS ARE

VERY INTERESTED IN BEING ASKED

WHETHER THEY'LL CONSENT TO HAVE

THEIR SPECIMENS USED IN RESEARCH

BUT ONCE YOU ASK THEM THEY

OVERWHELMINGLY AGREE TO ALLOW

THEIR TISSUE TO BE USED.

PEOPLE I DON'T THINK ARE QUITE,

THE ISSUE ISN'T REALLY THAT

PEOPLE WANT TO CONSENT, IT'S

THAT THEY WANT ENGAGEMENT.

THEY WANT TO BE INVOLVED AND

THEY WANT TO BE INCLUDED.

THEY WANT TO BE PARTNERS IN THE

RESEARCH PROCESS.

AND SO BECAUSE THE WAY

TRADITIONALLY THAT HAS BEEN DONE

IS THROUGH THE CONSENT PROCESS,

WE TEND TO FRAME THAT AS A

CONSENT ISSUE BUT IN FACT IT'S

REALLY AN ENGAGEMENT ISSUE AND

THE MORE WE CAN INVOLVE THE

PARTICIPANT COMMUNITY UP FRONT

IN STUDY DESIGN AND RESEARCH

GOING FORWARD AND RESEARCH

EFFORTS, THE LESS CRITICAL

THEY'LL FEEL ABOUT RECONTACTED

AND ASKED FOR SPECIFIC STUDIES

DOWN THE LINE.

PERHAPS THAT A POSITIVE WAY TO

GO INTO THE FUTURE.

>> ALL RIGHT, LET'S THANK ALL

OUR SPEAKERS.

THAT WAS REALLY INTERESTING

SESSION.

THANK YOU ALL FOR COMING.