THANK YOU FOR JOINING
US FOR TODAY'S OHSRP EDUCATION
SERIES SESSION TITLED OHSRP
EDUCATION SERIES SESSION: KEY
ETHICAL ISSUES IN PEDIATRIC
RESEARCH OUR SPEAKER FOR TODAY
IS DR. DAVID WENDLER.
A PHILOSOPHER WHO TRAINED
IN THE PHILOSOPHY
OF SCIENCE.
HE HAS BEEN AT THE NIH FOR 30
YEARS,
FIRST AS A FELLOW AND CURRENTLY
AS A SENIOR INVESTIGATOR AND
HEAD OF THE SECTION
ON RESEARCH ETHICS IN THE NIH
CLINICAL CENTER DEPARTMENT OF
BIOETHICS.
HE HAS WRITTEN WIDELY ON SUCH
TOPICS, ASSESSING
SYSTEMATICALLY, RESPECT FOR
AUTONOMY, ASSENT IN PEDIATRIC
RESEARCH, RESEARCH WITH STORED
BIOLOGICAL SAMPLES.
THE SLIDE WILL BE POSTED ON THE
NIH'S WEBSITE WANTED TO WEEK
LATER. THROUGHOUT THE SESSION
WE ENCOURAGE VIEWERS TO SUBMIT
QUESTIONS BY CLICKING ON THE
BOX BELOW THE VIDEO, TITLED
"LIVE THE FEEDBACK LINK."
PLEASE GO AHEAD AND I WILL LET
YOU GET STARTED.
>> DR. WENDLER: THANKS PEG. AND
THANKS FOR HAVING ME. I'M
GOING TO TALK ABOUT KEY ETHICAL
ISSUES IN PEDIATRIC RESEARCH.
BUT I WILL TRY TO DO IS GIVE A
GENERAL CONSENSUS VIEWS. BUT
ALSO AS YOU ARE SEEING IN A
NUMBER OF PLACES, I'M GOING TO
GIVE YOU MY OWN VIEWS, WOULD
SOMETIMES ARE SIMILAR TO THE
CONSENSUS USE. SOMETIMES WILL
BE DIFFERENT. I WILL TRY TO
FLAG THOSE DIFFERENCES AND THEN
WE CAN DISCUSS THEM IF PEOPLE
ARE INTERESTED.
IN TERMS OF THE ISSUES I AM
GOING TO FOCUS ON THESE FIVE, I
SHOULD SAY THAT I HAVE TALKS
THAT TAKE AN HOUR FOR EACH ONE
OF THESE FIVES. TODAY, OUT OF
NECESSITY, WILL DO A HIGH-LEVEL
GENERAL ASSESSMENT OF EACH OF
THEM IN THEN I'M HOPING TO
LEAVE SOMETIME AT THE END TO
ALLOW US TO FOCUS IN ON THE
ONES THAT PEOPLE FIND THE MOST
INTERESTING. OR THE MOST
PRESSING.
FIRST THE IMPORTANCE OF
PEDIATRIC RESEARCH. THIS ONE
HOPEFULLY FOR THIS AUDIENCE
SHOULD BE RELATIVELY
STRAIGHTFORWARD.
AS EVERYBODY KNOWS, INFORMED
CONSENT IS AT LEAST ONE OF, IF
NOT THE KEY ETHICAL SAFEGUARDS
FOR CLINICAL RESEARCH. AND THAT
RAISES CONCERNS ABOUT WHAT WE
DO TO PROTECT INDIVIDUAL CAN'T
GIVE INFORMED CONSENT. SOME
REGULATIONS AND GUIDELINES
PROHIBIT THEIR ENROLLMENT AS A
MEANS OF PROTECTION. THE
EXAMPLE HERE IS A NüRNBERG CODE
WHICH PEOPLE MIGHT KNOW TALK
ABOUT THE INFORMED CONSENT OF
THE INDIVIDUAL BEING WHAT IS
CALLED "ESSENTIAL" TO ETHICAL
RESEARCH SUGGESTING YOU SHOULD
NOT ENROLL PEOPLE WHO CAN'T
CONSENT.
THAT APPROACH HAS A NUMBER OF
VIRTUES. IT OFFERS STRONG
PROTECTION FOR INDIVIDUAL CAN'T
CONSENT, FROM BOTH EXPLOITATION
AND FROM BEING EXPOSED TO
EXCESSIVE RESEARCH RISKS AND
CANNOT BE ENROLLED IN RESEARCH,
AND CANNOT BE EXPOSED IN
EXCESSIVE RESEARCH RISKS.
IT HAS OBVIOUSLY IMPORTANT
DOWNSIDE. IF YOU'RE NOT ALLOWED
TO BE IN RESEARCH, YOU CANNOT
ENGAGE IN STUDIES THAT MIGHT BE
BENEFICIAL TO YOU. FOR EXAMPLE
PEOPLE WHO HAVE A CONDITION FOR
WHICH THERE IS NO APPROVED
TREATMENT, SOMETIMES CAN
BENEFIT SIGNIFICANTLY FROM
ROLLING ON A RESEARCH TRIAL.
AND THEY ARE PREVENTED FROM
THIS APPROACH. ALSO UNDERMINES
RESEARCH ON THE CONDITIONS
WHICH AFFECT THESE INDIVIDUALS
IN TRYING TO FIND A BETTER AND
IMPROVED TREATMENTS FOR THEM.
SO THAT LED US-- THIS
PROTECTIONIST MODE LED US TO
THE SITUATION WE ARE IN WHICH
TODAY. ESTIMATES VARY, 60 TO
80%, A LOT OF INTERVENTIONS
USED IN CHILDREN HAVE NOT BEEN
ASSESSED SYSTEMATICALLY,
EVALUATED AND TESTED AND
APPROVED IN CHILDREN. INSTEAD,
THEY HAVE BEEN TESTED IN ADULTS
AND JUST BEING USED IN
CHILDREN. BUT OF COURSE
CHILDREN ARE NOT
PHYSIOLOGICALLY JUST LITTLE
ADULTS. AND THAT IS PROBLEMATIC.
WHAT WE NEED TO DO INSTEAD TO
IMPROVE PEDIATRIC CLINICAL
CARE, IS WE NEED PEDIATRIC
RESEARCH. SO WE NEED TO ENROLL
MINORS IN RESEARCH. AND IF WE
ARE GOING TO DO THAT IN AN
ETHICAL WAY, WE NEED TO FIGURE
OUT WHAT THE CONDITIONS ARE.
THOSE ARE THE ONES THAT I AM
GOING TO TALK ABOUT TODAY, ARE
DOING THIS IN AN ETHICALLY
APPROPRIATE WAY.
WHAT ARE CALLED NET RISK
PEDIATRIC RESEARCH. AT A
GENERAL LEVEL THIS IS THE
PRIMARY ETHICAL CONSIDERATION
AND CONCERNED COMES UP WHEN YOU
THINK ABOUT ENROLLING CHILDREN
IN RESEARCH.
TO START WITH THE ONES THAT
DON'T SEEM AS PROBLEMATIC,
PROSPECT OF BENEFIT, THE US
RELATIONS CALL THIS PROSPECT OF
DIRECT BENEFIT, IT IS WIDELY
AGREED THAT IT CAN BE ETHICAL
TO UNROLL CHILDREN IN RESEARCH
EVEN THOUGH THEY CAN'T CONSENT.
WHEN THE RESEARCH HAS
IMPORTANT SOCIAL VALUE AND IT
ALSO OFFERS THE PARTICIPANTS
THE PROSPECT OF A BENEFIT.
I WILL TAKE THE OPPORTUNITY TO
BEAT A COUPLE OF DRUMS. THIS IS
ONE BEFORE WE GET TO NET RISK,
JUST TO SAY THAT QUALIFYING AS
PROSPECT OF DIRECT BENEFIT OF
RESEARCH IS NOT SUFFICIENT THAT
THE RESEARCH JUST OFFERS ANY
CHANCE OF POTENTIAL BENEFIT TO
PARTICIPANTS. INSTEAD AND I
THINK THIS IS A PLACE WHERE THE
US REGULATIONS ARE CLEAR, AND
ESSENTIALLY RIGHT, YOU HAVE TO
SATISFY THESE TWO CONDITIONS.
NOT JUST THAT THERE IS SOME
POTENTIAL FOR BENEFIT THE
PARTICIPANTS. BUT THAT THE
POTENTIAL BENEFITS FOR THE
PARTICIPANTS JUSTIFY THE RISKS
THAT THEY FACE.
AND ALSO THEY HAVE TO CONVEY
THE ALTERNATIVES. THE
RISK-BENEFIT PROFILE OF BEING
IN THE RESEARCH, THESE ARE THE
WORDS OF THE US REGS, AT LEAST
AS FAVORABLE AS THE AVAILABLE
ALTERNATIVES. IF THERE ARE
NOT, THERE IS A SENSE IN WHICH
THEY WOULD BE BETTER OFF BEING
OUTSIDE OF THE RESEARCH AND
JUST GETTING CLINICAL CARE. SO
THAT IS THE CLINICAL PROSPECT
OF BENEFIT.
WHAT ABOUT RESEARCH STUDIES
THAT DON'T SATISFY THESE
CONDITIONS? THESE ARE STUDIES
WHERE THE POTENTIAL BENEFITS TO
PARTICIPANTS DON'T JUSTIFY THE
RISKS. OR TO PUT IT THE OTHER
WAY, THE RISKS EXCEED THE
POTENTIAL BENEFITS. AND JUST
FOR CONVENIENCE OUR CALL THESE
NET RISK STUDIES OR NET RISK
PEDIATRIC RESEARCH. PEOPLE USE
DIFFERENT TERMS.
HERE ARE EXAMPLE OF THINGS
WHERE YOU ARE GOING TO GET A
PURELY RESEARCH BLOOD DRAW, OR
PURELY RESEARCH SKIN BIOPSY.
WE DID SOME EVALUATIONS WE
STUDY ABOUT FIVE YEARS AGO,
WHERE THEY WERE JUST ENROLLING
HEALTHY TEENS INTO AN MRI
STUDY, JUST TO LOOK AT THEIR
BRAINS AND THEN COMPARE THEM TO
THE BRAINS OF PEOPLE WITH
AUTISM. THOSE SCANS FOR THE
HEALTHY VOLUNTEERS DID NOT DID
ANYTHING, AND THEY WERE HIGH
RISKS. THAT QUALIFIES UNDER
THE SCHEME OF NET RISK
PEDIATRIC RESEARCH.
THIS WAS THE BIGGEST DEBATE.
FOR PEOPLE WHO KNOWS THE
FEDERAL REGULATIONS AS WE HAVE
THEM TODAY TRACE TO THE WORK OF
THE US NATIONAL COMMISSION IN
THE 1970S. THIS WAS THE
BIGGEST FIGHT AND THE BIGGEST
DEBATE. ACTUALLY THE ONE THAT
LED TO A COUPLE OF PUBLIC
DISAGREEMENTS THAT WERE
WRITTEN, AND ARE INTERESTING
READING FOR ANYBODY LIKE THAT
SORT OF STUFF. AND THAT DEBATE
CONTINUES TODAY.
HERE'S SOME DATA FROM ABOUT 15
YEARS AGO. STUDIES THAT
SUGGESTED THAT PEDIATRICIANS
AND RESEARCH IN CANADA AND THE
UK, ALMOST HALF OF THEM
THOUGHT WHAT I AM CALLING NET
RISK RESEARCH WAS UNACCEPTABLE
AND CANADIAN MEDICAL STUDENTS
AND SEEM TO HAVE A SIMILAR
VIEW. SO WE NEED TO ASSESS THEM
AND FIGURE OUT WHEN THE
RESEARCH IS ACCEPTABLE.
SO HOW DO WE TRY TO ADDRESS
THIS? THE US RELATIONS DO THIS
THAT INITIALLY STRIKES ME AS A
GOOD IDEA. WHAT THEY SAID IS,
WE'RE WORRIED ABOUT THESE NET
RISKS OF PEDIATRIC RESEARCH.
TO EVALUATE THEM LET'S COMPARE
THEM TO OTHER RISKS THAT
CHILDREN FACE THAT WE THINK ARE
ACCEPTABLE. AND THE REGS DO
THIS IN TERMS OF THE RISKS OF
DAILY LIFE, RISKS ORDINARILY
ENCOUNTERED IN DAILY LIFE.
NOW, HERE IS MY PERSONAL SHTICK
ON THE MINIMAL RISK STANDARD.
A LOT OF THE RISKS THE CHILDREN
TO PACING DAILY LIFE ARE
ASSOCIATED WITH ACTIVITIES THAT
HAVE BENEFITS. LIKE YOUR
PARENTS TAKE YOU SNOW SKIING.
IF YOU'RE LUCKY SNOW SKIING IS
A FAIRLY RISKY ENDEAVOR. THE
REASON WHY PARENTS THINK THAT
IS ACCEPTABLE FOR THEIR
CHILDREN IS BECAUSE THEY ASSUME
THE CHILDREN ARE GOING TO ENJOY
IT. AND SO THE RISKS OF THOSE
SORTS OF ACTIVITIES, ACTIVITIES
THAT BENEFIT PARTICIPANTS,
DON'T SEEM LIKE A GOOD STANDARD
FOR DETERMINING WHICH RISKS ARE
ACCEPTABLE IN THE CONTEXT OF
NET RISK PEDIATRIC RESEARCH.
NAMELY RESEARCH THAT DOES NOT
BENEFIT THE PARTICIPANTS.
MY RESPONSE AND THIS IS WHAT I
CALL THE "CHARITABLE"
PARTICIPATION STANDARD.
INSTEAD OF COMPARING THE RISKS
OF PEDIATRIC RESEARCH TO ANY
RISKS THAT CHILDREN FACE IN
DAILY LIFE, WE SHOULD INSTEAD
MORE NARROWLY COMPARE THE RISK
OF RESEARCH COMPARED TO
ACTIVITIES DESIGNED BY OTHERS.
OBVIOUS EXAMPLES LIKE CHARITY
CARWASH, CHARITY SPORTING
EVENTS, SHOVELING A NEIGHBOR'S
SIDEWALK, TAKING A NEIGHBOR TO
THE HOSPITAL OR TAKING YOUR
NEIGHBOR TO THE GROCERY STORE
OR ACTIVITIES THAT ARE INTENDED
TO BENEFIT SOMEBODY ELSE. AND
POSE AT LEAST SOME BURDENS AND
RISKS ON MINORS WHEN THEY ARE
INVOLVED IN THAT.
THE THOUGHT IS THAT IS A BETTER
WAY FOR ASSESSING THE RISKS OF
NET RISK PEDIATRIC RESEARCH.
THAT RAISES THE QUESTION. WHEN
I FIRST STARTED WORKING IN
THIS, A LOT OF PEOPLE OBJECTED
THAT THE RISKS OF RESEARCH WERE
COMPLETELY DIFFERENT THAN
CHARITABLE ACTIVITIES. AND WE
CANNOT COMPARE THEM. WITH A
NUMBER OF STUDIES TO SEE
WHETHER OR NOT PARENTS AND
ADOLESCENTS AGREED WITH THAT
VIEW AND WHAT THEY THINK OF THE
RISKS OF RESEARCH VERSUS THE
RISK OF CHARITABLE ACTIVITIES.
HERE IS A LITTLE BIT OF DATA
FROM ONE OF THOSE STUDIES. AND
WHAT IS INTERESTING ABOUT THIS,
WHAT IT SHOWS IS FOR THE
PARENTS, IF YOU LOOK AT THE
FAR-RIGHT COLUMN, WHAT PARENTS
CARE ABOUT IS THEY CARE ABOUT
THE RISKS THEIR KIDS FACE NOT
TO WORRY ABOUT THE CONTEXT. WE
ASKED THEM HOW DO YOU FEEL
ABOUT YOUR CHILDREN FACING A
GIVEN RISK IN A RESEARCH STUDY,
VERSUS FACING THE SAME RISK IN
A CHARITABLE ACTIVITY, THE
PARENTS WERE BASICALLY
INDIFFERENT FOR THE MOST PART.
ALMOST 90% WERE EQUALLY WILLING
IN THE TWO CASES. THEY DON'T
SEE ETHICAL DIFFERENCES BETWEEN
CHARITABLE ACTIVITIES AND
RESEARCHER ACTIVITIES. WHAT IS
INTERESTING IS THE ONES THAT
HAD A DIFFERENT VIEW. IT
SUGGESTED THAT TEENS AND
PARENTS DON'T REGARD THESE
RISKS DRAMATICALLY DIFFERENT IN
AN ETHICAL SENSE AND SUGGESTS
THAT THE RISK OF CHARITABLE
ACTIVITIES CAN COMPARE A WAY TO
PROPERLY ASSESS THESE PEDIATRIC
RISKS.
THIS WAS A SHOCK FROM ONE OF
OUR PREVIOUS FELLOWS. WE WERE
LOOKING TO SEE WHAT A
REPRESENTATIVE SAMPLE OF THE US
PUBLIC THINGS ABOUT VARIOUS
ASPECTS OF NET RISK PEDIATRIC
RESEARCH. BASICALLY WHAT WE
DID IS WE GAVE THEM A NUMBER OF
DIFFERENT PROCEDURES THAT MIGHT
BE DONE IN A NET RISK PEDIATRIC
RESEARCH SETTING AND WE ASK
THEM WHAT THEY THOUGHT OF THE
APPROPRIATENESS OF THOSE
PROCEDURES. AND WHAT WE FOUND
WAS VERY HIGH, MID EIGHTIES,
LOW NINETIES SUPPORT TO NET
RISK PEDIATRIC RESEARCH. NOT
SURPRISINGLY THE SUPPORT WENT
DOWN A LITTLE BIT AS THE RISKS
WENT UP.
BUT ALSO INTERESTINGLY, AND
THIS IS SOMETHING THAT THE US
REGS REALLY DON'T ACCOUNT FOR
IN THE WAY WE THINK IS
APPROPRIATE AND THIS WAS ONE OF
THEIR POINTS THAT WILL WAS VERY
INTERESTED IN THIS RESEARCH
WHICH. ACCORDING TO A SAMPLE OF
THIS THEY FELT THAT HIGHER
RISKS, FOR EXAMPLE SOMEWHAT
HIGHER THAN A MINOR INCREASE
OVER A MINIMAL RISK, CAN BE
ACCEPTABLE IN CASES WHERE THE
RESEARCH HAD AN ESPECIALLY HIGH
SOCIAL VALUE.
THE POINT IS THAT ONE, THE US
PUBLIC IS SUPPORTIVE OF THIS
TYPE OF RESEARCH. THE SECOND
THING IS TO NOTE THAT THERE IS
A GREAT EMPHASIS ON ENSURING
THAT THE RESEARCH IS NOT JUST
APPROPRIATE WITH RESPECT TO
RISK. BUT THAT IT DOES IN FACT
HAVE AN IMPORTANT SOCIAL VALUE.
SOMETHING VALUABLE TO YOU WILL
LEARN AS A RESULT OF RESEARCH.
NOW THIS TO LEASE THE
PHILOSOPHICAL QUESTION OF WHY
IS IT? THIS SUGGESTS THE DATA
THAT PEOPLE THINK THESE RISKS
ARE ACCEPTABLE IN THE SUBWAY
FOR ASSESSING THE RISK BUT IT
LEAVES PHILOSOPHICAL QUESTION
OF WHY IS IT ACCEPTABLE TO
EXPOSURE AND RISK, EITHER IN
RESEARCH OR ANY CHARITABLE
ACTIVITY, TO RISK FOR THE
BENEFIT OF OTHERS? I WON'T GO
TO THAT HERE BUT THERE I WROTE
AN ENTIRE BOOK ON THIS FOR
PEOPLE WHO ARE INTERESTED HERE
IS A REFERENCE. AND YOU CAN
DRAMATICALLY INCREASE THE SALES
OF BOOK JUST BY ONE PURCHASE
FOR YOURSELF.
THE NEXT THING IS EVALUATING
RISKS. THAT WAS PEDIATRIC
RESEARCH. HOW ABOUT EVALUATING
RISKS? HOW DO WE DO THAT?
I WOULD LIKE SOME QUOTE FROM
THE BELMONT REPORT, AND YOU CAN
READ THROUGH THESE BUT
BASICALLY THIS IS THE BELMONT
REPORT ONE OF THE GUIDING
DOCUMENTS FOR IRBS. THE POINT
HERE IS WHAT THEY ARE SAYING
WHICH I THINK IS ABSOLUTELY
RIGHT. AND I THINK WE STILL
DON'T DO IN THE WAY WE SHOULD,
IS THAT WE SHOULD
SYSTEMATICALLY EVALUATE RISKS
AND BENEFITS. WE SHOULD JUST
NOT USE OUR INTUITIONS TO GUESS
WHETHER OR NOT WE THINK FOR
INSTANCE A PROCEDURE, AN MRI, A
LUMBAR PUNCTURE. INSTEAD WHAT
WE SHOULD DO IS REALLY EVALUATE
THAT, IN A VERY SYSTEMATIC WAY.
THIS IS A SERVER FROM A LONG
TIME AGO FROM SHAH, THE FELLOW
HERE.
WE SURVEYED PEDIATRIC IRB
CHAIRPERSONS. WE ASKED WHAT
THEY THOUGHT OF THE RISK LEVEL
WAS. THIS IS SURVEY. PEDIATRIC
RESEARCH PROCEDURES, WHAT DID
THEY THINK THE RISK LEVEL OF
THOSE PROCEDURES WAS?
IF WE LOOK AT THE MIDDLE ROW,
ALLERGY SKIN TESTING, WHAT YOU
GET IS FAIRLY DISMAYING. IS AN
INCREDIBLE SPREAD. THESE ARE
EXPERIENCED PEDIATRIC IRB
CHAIRPERSONS, BUT THERE IS AN
AMAZING SPREAD WHETHER THEY
THINK ALLERGY SKIN TESTING IS
MINIMAL. WHY IS THAT GOING ON?
WE SPECULATE THAT IT IS BECAUSE
WHAT IRB CHAIRPERSONS AND
OTHERS ARE DOING WHEN THEY
EVALUATE THE RISKS OF PEDIATRIC
RESEARCH ISN'T WHAT THE BELMONT
REPORT SUGGESTED. IT IS NOT
DOING IT IN A SYSTEMATIC WAY
DRIVEN BY DATA. INSTEAD IT IS
RELYING ON INTUITIONS. AND
UNFORTUNATELY PEOPLE HAVE
DIFFERENT INTUITIONS. I GUESS
NOT SURPRISINGLY ON THESE
THINGS.
THAT IS NOT GOING TO GET IS
VERY FAR. WHAT WE NEED TO DO?
I THINK IT STARTS WITH COMING
BACK TO THE DEFINITION.
HOPEFULLY EVERYBODY'S FAMILIAR
WITH THIS. THIS IS THE
DEFINITION FROM THE FEDERAL
REGS OF MINIMAL RISK.
I THINK WE NEED TO DO TWO
THINGS. FIRST WE NEED TO
UNDERSTAND THE DEFINITION. AND
SECOND IS, FIGURING OUT A WAY
TO IMPLEMENT IT SYSTEMATICALLY.
TO AT LEAST APPROACH THE
BELMONT IDEAL.
SO TWO MISINTERPRETATIONS THAT
I HAVE ENCOUNTERED A LOT OVER
THE YEARS. THE FIRST IS THAT
WHAT SOME PEOPLE THINK THAT THE
MINIMAL RISK DEFINITION IS IS
YOU ASSESS WHETHER OR NOT
CHILDREN ORDINARILY ENCOUNTER
THE SPECIFIC PROCEDURE IN DAILY
LIFE. AND IF THEY DON'T THAT
PROCEDURE QUALIFIES IS MORE
THAN MINIMAL RISK.
I KNOW PEOPLE KNOW REIKI. BUT
THIS IS A TECHNIQUE WHERE YOU
BASICALLY PUT YOUR HANDS ABOVE
THE BODY OF THE PATIENT AND
YOU'RE SUPPOSED TO TRY TO
TRANSMIT POSITIVE ENERGY TO
THEM, AND SUBTRACT SOME
NEGATIVE ENERGY FROM THEM. AND
I THINK IF ANY RESEARCH
PROCEDURE QUALIFIES AS MINIMAL
RISK, THIS ONE CERTAINLY DOES.
I CANNOT SEE HOW THERE ARE ANY
RISKS AT ALL. BUT IT IS NOT A
PROCEDURE THE CHILDREN
ORDINARILY ENCOUNTER IN THEIR
LIVES. BUT IT WOULD BE A
MISTAKE THAT A STUDY OF REIKI
IS MORE THAN MINIMAL RISK.
HOW DO WE AVOID THAT? GOING
BACK TO THE DEFINITION AND
COMPARING THE LEVEL OF THE
PROBABLY OF MAGNITUDE AND HARM
TO THE LEVEL OF THE RISKS OF
DAILY LIFE SO IT IS NOT A TYPE
OF PROCEDURE BUT THE LEVEL OF
THE RISKS THAT IS SUPPOSED TO
BE GETTING COMPARED.
ANOTHER MISINTERPRETATION. I
THINK SOME PEOPLE WHEN THEY TRY
TO IMPLEMENT THE MINIMAL
STANDARD THEY ASK THEMSELVES,
IS THERE ANY CHANCE OF
SIGNIFICANT HARM? I THINK THAT
IS ALSO A MISTAKE.
THE FACT THAT THERE IS ANY
CHANCE OF HARM DOES NOT MEAN
THAT A PROCEDURE IS MORE THAN
THE RISK. IT DEPENDS ON HOW
LIKELY THAT IS. SOMETHING OF
HAVING THE CHANCE OF
SIGNIFICANTLY HARM, AND STILL
BE MINIMAL RISK IS IF THAT
CHANCE IS MINIMALLY LOW. AND WE
CAN TALK ABOUT THAT MORE PEOPLE
ARE INTERESTED.
THOSE ARE THE TWO
MISINTERPRETATIONS. TRYING TO
UNDERSTAND THE DEFINITION
FIRST.
AND THE SECOND THING THAT I
WILL MENTION IS BRIEFLY, WHAT
WE NEED THEN IS METHODS FOR
COMPARING THEM. FOR ACTUALLY
IMPLEMENTING THE DEFINITION.
AND THAT REQUIRES THREE THINGS.
IT REQUIRES DATA ON THE RISKS
OF THE RESEARCH PROCEDURE. FOR
INSTANCE AN MRI, IF IT IS AN IV
GLUCOSE TOLERANCE TEST, A
LUMBAR PUNCTURE, DATA ON THE
RISKS OF CHARITABLE ACTIVITIES
AND A WAY FOR SYSTEMATIC
EVALUATION OF RESEARCH RISKS.
THIS IS A METHOD THAT WE HAVE
COME UP TRYING TO DO THAT
COMPARISON.
WORKING ON THIS A LITTLE BIT
COMPLICATED BUT THE POINT IS TO
SUGGEST THAT AT LEAST IN
PRINCIPLE THERE ALWAYS TO GET
CLOSER TO WHAT BELMONT IS
DIRECTING IRBS TO DO.
HOW ABOUT PEDIATRIC ASSENT? AS
PEOPLE ARE PROBABLY AWARE OF US
RELATIONS REQUIRE THE
AFFIRMATIVE AGREEMENT, THE
ASSENT, PROVIDING THAT CHILDREN
ARE CAPABLE OF PROVIDING IT.
AND WHAT THE REGS GIVES US, IS
CAPABLE IS THIS: AGE, MATURITY
AND PSYCHOLOGICAL STATE OF THE
CHILDREN.
A LITTLE BIT BUT NOT TERRIBLY
HELPFUL. HOW DO PEOPLE
IMPLEMENT THIS?
A LOT OF PEOPLE DO WHAT SOME
PEOPLE REFER TO AS A RULE OF
SEVENS. THE IDEA IS THAT AT
THE AGE OF 7, CHILDREN BECOME
CAPABLE OF ASSENT. THIS RULE
OF 7S, LOOKS LIKE IT TRACES TO
ENGLISH COMMON LAW AND THE
1300-1400S. I SAW A REFERENCE
THAT IT MIGHT GO BACK TO MIDDLE
EASTERN LAW, HUNDREDS AND
HUNDREDS YEARS BEFORE THAT.
LOOK LIKE A VERY OLD IDEA BUT
NOT SURE IT GIVES US WHAT WE
WANT.
US COG, THE ONCOLOGY GROUP,
THEY SUGGEST NOT SEVEN BUT
INCREASED TO NINE. WE HAVE TO
FIGURE OUT WHEN IT IS
APPROPRIATE AND WHAT WE ARE
GETTING ASSENT FROM CHILDREN
AND HERE'S SOME DATA FROM A
LONG TIME AGO FROM US. WHICH
SUGGESTED THAT HALF OF IRBS
NEEDED OPTIMIST IS TO DECIDE
WHETHER OR NOT A GIVEN CHILD
CAN ASSENT OR NOT.
OTHERS PICK IN AGE CUT OFF. AND
AS YOU CAN SEE HERE THAT VARIES
ANYWHERE FROM 7, SOME ACTUALLY
USE 5, SOME UP TO 14. IT
VARIES FAIRLY WIDELY.
SO HERE'S OUR THOUGHT. WHAT YOU
SHOULDN'T DO IT SHOULDN'T ASK
CHILDREN TO MAKE DECISIONS
THEY DON'T UNDERSTAND. THAT IS
NOT PROBLEMATIC. IT IS A
MATTER OF RESPECT INCREASES THE
CHANCES OF BAD RESEARCH.
WE SHOULD BE ASKING CHILDREN AT
THE POINT IN WHICH THEY CAN
UNDERSTAND THE BASICS OF
RESEARCH AND THERE IS A FAIR
AMOUNT OF DATA, MAYBE NOT
ENOUGH, TO SUGGEST THAT MAYBE
THAT AGE IS PROBABLY AROUND
SOMEWHERE BETWEEN 12 AND 14.
AND THIS IS WHERE MY VIEW
DIVERGES A FAIR AMOUNT FROM
CONSENSUS.
MOST PEOPLE IN PEDIATRIC
RESEARCH ETHICS IF THEY WERE
GIVEN A TALK THEY WOULD
RECOMMEND A MUCH LOWER AGE THAN
THAT. BUT IF YOU THINK WHILE WE
ARE ASKING FOR THIS, IT MIGHT
SUGGEST A HIGHER ONE.
ONE PROBLEM WITH THIS IS THAT
IN A LOT OF CASES WHERE THE US
REGULATIONS DO, AND I ALSO
THINK IRBS SOMETIMES FALL INTO
THIS TRAP TOO, IS A TETHER
TOGETHER INFORMING INDIVIDUALS
ABOUT A STUDY AND OBTAINING
THEIR AGREEMENT. THE IDEA IS
THAT WE ONLY INFORM PEOPLE
ABOUT THEIR AGREEMENT AND
INFORMED ABOUT THE THINGS WE
WANT THEIR AGREEMENT FOR.
HERE IS ONE OF MY "OTHER"
DRUMS, I'M GOING TO BEAT FOR A
SECOND. ONE RESULT OF THIS IF
YOU LOOK AT THE INFORMED
CONSENT FORMS, WE ALL BEMOAN
THIS, BUT THEY ARE LONG AND
INCLUDE JUST COPIOUS AMOUNTS OF
INFORMATION. AND THEY INCLUDE I
THINK A LOT OF INFORMATION THAT
JUST ISN'T RELEVANT FOR THE
CONSENT FORM, WHICH IS WHETHER
OR NOT PEOPLE SHOULD BE
ENROLLED IN A TRIAL.
ON TUESDAY AT 2 PM YOU HAVE TO
SHOW UP. BUT ON WEDNESDAYS IT
IS A 3. EVERY OTHER FRIDAY WE
TAKE OFF AND SO WE KNOW THOSE
ARE IMPORTANT THINGS THAT ARE
IMPORTANT FOR PEOPLE IN THE
TRIAL TO KNOW. BUT IN MOST
CASES IT IS NOT RELEVANT. IT
MAY BE DISTRACTING FOR PEOPLE
TO BE GIVEN THAT INFORMATION IN
A CONSENT FORM WHEN THEY ARE
TRYING TO DECIDE WHETHER TO
ENROLL IN THE FIRST PLACE. AND
ASKED THINK HE'S TIED TOGETHER
OF INFORMING PEOPLE CAUSES A
PROBLEM THERE.
THE OTHER THING IS I AM SAYING
WE SHOULD NOT OBTAIN ASSENT
UNTIL THE CHILD IS 12-14. SO
IF THE CHILD IS 5, 6, 7, 8, WE
SHOULD NOT TELL THEM ABOUT THE
RESEARCH? THAT IS PROBLEMATIC.
IT SHOULD NOT HAVE THAT
IMPLICATION. INSTEAD WHAT WE
NEED TO DO IS TO BREAK APART
WHAT WE WANT TO INFORM PEOPLE
ABOUT AND WHEN WE ARE GETTING
THERE AGREEMENT.
HOW DO WE DO THIS? MY
SUGGESTION IS TO PROVIDE
AGE-APPROPRIATE INFORMATION TO
ALL CHILDREN WHETHER YOU ARE
GOING TO ASK FOR ASSENT OR NOT,
WHETHER 5 OR 15. IF YOU'RE
GOING TO ASK FOR THEIR ASSENT,
YOU ASK IF THEY'RE WILLING TO
PARTICIPATE. IF THEY ARE NOT
ASSENTING, OR NOT REQUIRING
THEIR ASSENT, YOU ARE GIVING
THEM THE INFORMATION ASKING IF
THERE ARE QUESTIONS OR CONCERNS
AND IF THEY DON'T PARTICIPATE
AND MONITOR THEM ANY QUESTIONS
COME UP, YOU TRY TO ADDRESS
THOSE OBJECTIONS.
OKAY. COMPENSATION. I THINK
PEOPLE LISTENING TO THIS
REALIZE THAT THERE ARE A LOT OF
CONCERNS REGARDING
CONVERSATIONS.
INTERESTING BECAUSE
CONVERSATION IS ONE OF THE RARE
PLACES I THINK WHERE
INVESTIGATORS AND IRB MEMBERS
TEND TO BE MORE CONCERNED THAN
PEOPLE LIKE ME WHO DO RESEARCH
ETHICS. PEOPLE IN OUR
DEPARTMENT TEND TO BE FAIRLY
SUPPORTIVE, RATHER THAN
SUSPICIOUS OF COMPENSATING
RESEARCH PARTICIPANTS. BUT
HERE'S SOME EXAMPLES OF SOME OF
THE SUSPICIONS.
I DON'T KNOW IF PEOPLE ARE
FAMILIAR WITH THIS. THE SECOND
ONE IS FROM THE MARYLAND COURT
OF APPEALS, THE HIGHEST COURT
IN MARYLAND, IN RESPONSE TO THE
GRIMES VERSUS KENNY KRIEGER
INSTITUTE RELATED TO A PAIN
STUDY THAT PEOPLE MAY KNOW
ABOUT THAT RECEIVED A LOT OF
ATTENTION. THEY WENT TO THIS
COURT AND THERE WAS A LOT OF
HUMAN CRY. AND THE COURT
INITIALLY WAS EXTREMELY
SKEPTICAL OF THE STUDY TO THE
POINT OF ALMOST BEING SCATHING.
THEY SAID THE PARENTS WERE
RATHER IMPROPERLY ENTICED. IT
IS A MISTAKE. BUT YOU CAN
NOTICE HERE THAT THERE IS
ENTICING WITH MONEY. WHAT MONEY
IS DOING IS GETTING PARENTS TO
DO THINGS WITH AND FOR THEIR
CHILDREN AND TO THEIR CHILDREN
THAT ARE IMPROPER.
A FAIR NUMBER OF THE OBJECTIONS
FOR PAYING FOR PEDIATRIC
RESEARCH REFLECT NOT ONLY
OBJECTIONS TO PAYMENT, BUT
INSTEAD REFLECT OBJECTIONS TO
THE RESEARCH ITSELF. AND THAT
IS NOT SURPRISING. IF YOU DON'T
LIKE A PARTICULAR STUDY, IF YOU
THINK A PARTICULAR STUDY IS
UNETHICAL OR PROBLEMATIC,
YOU'RE NOT GOING TO LIKE PAYING
PARENTS TO ENROLL THEIR
CHILDREN IN THE RESEARCH. AND
THAT IS A LEGITIMATE CONCERN.
BUT I WANT TO DO IS FOCUS ON
STUDIES WHERE WE THINK THAT
THEY ARE ETHICALLY APPROPRIATE
AND WHETHER PAYMENT IS INVOLVED
OR NOT, OBVIOUSLY IRBS NEED AND
THEIR CHARGES NEED TO MAKE SURE
THAT THE RESEARCHERS REVELATORY
AND ETHICALLY APPROPRIATE. THAT
IT IS SOCIALLY, SCIENTIFICALLY
VALUABLE; RIGOROUS AND VALID,
THAT THE RISKS ARE ACCEPTABLE
AND ASSENT IS OBTAINED WHEN IT
SHOULD BE OBTAINED AND IT IS
BEING RESPECTED, AND ALL THE
OTHER REQUIREMENTS.
AND SO THE QUESTION THEN IS,
WHAT DO WE THINK? AND WHAT ARE
THE ETHICS OF COMPENSATION?
WHEN ALL OF THESE CONDITIONS
ARE SATISFIED.
SO, ONE WORRY I THINK IS THIS.
WHICH IS THAT AS WE ALL KNOW,
IRBS EVALUATE AT LEAST INITIAL
REVIEWS AND EVALUATE RESEARCH
PROTOCOLS PROSPECTIVELY. THE
EVALUATE BEFORE ANY CHILDREN
ARE INVOLVED AT ALL. HOW DO
YOU FIGURE OUT WHAT THE RISKS
ARE IF YOU DON'T KNOW WHO IS
GOING TO BE ENROLLED?
YOU LOOK AT THE INCLUSION/
EXCLUSION CRITERIA. YOU FIGURE
OUT WHAT THE POPULATION IS THAT
SATISFIES THOSE CRITERIA. AND
YOU BASE YOUR RISK JUDGMENT ON
THAT.
SO, THAT IS PRESUMABLY
ACCEPTABLE, PROBABLY IN MOST
CASES. THE PROBLEM IS THERE
MIGHT BE SOME CASES WHERE FOR
SOME OF THE SPECIFIC
INDIVIDUALS WITHIN THE
POPULATION, THAT SATISFIES THE
INCLUSION/ EXCLUSION CRITERIA,
IT MIGHT BE WHAT YOU THINK OF
IDIOSYNCRATIC CIRCUMSTANCES.
THEY MAY HAVE A HISTORY OR
COMORBIDITY, OR TREATMENTS THEY
ARE TAKING OR SOMETHING ELSE IN
THE CIRCUMSTANCES OR THE
CONDITION OF THEIR HEALTH WHICH
RAISES CONCERNS OR GREATER
RISKS FOR THEM THAN OTHER
PEOPLE WHO ARE ELIGIBLE FOR THE
STUDY.
AND THAT IS A POSSIBILITY, THE
NOTHING THIS IS A CASE WHERE WE
NEED TO START THINKING ABOUT
INDIVIDUALIZED ASSESSMENT OF
SPECIFIC INDIVIDUALS WHERE THE
CHILDREN DON'T GET ENROLLED.
UNTIL WE MAKE SURE THE RISKS
ARE APPROPRIATE FOR THEM.
THAT IS A WAY TO PUT OFF AT
LEAST ONE OF THE OBJECTIONS TO
PAYMENT. WHICH IS THERE MIGHT
BE SPECIFIC INDIVIDUALS, EVEN
IF THE OVERALL STUDY IS
ACCEPTABLE. THERE MIGHT BE
SPECIFIC INDIVIDUALS FOR WHOM
THE STUDY IS INAPPROPRIATE.
AND THIS IS AT LEAST ONE WAY TO
TRY TO ADDRESS THAT.
OKAY SO NOW WE ARE SUPPOSED TO
IMAGINE WE HAVE DONE ALL OF
THAT AND WE ARE FAIRLY
CONFIDENT THAT THE STUDY IS
ACCEPTABLE ACCORDING TO ETHICAL
CONSIDERATIONS.
AND THE QUESTION IS WHAT WE
THINK ABOUT COMPENSATION OR
PAYMENT WITHIN THAT CONTEXT FOR
THOSE STUDIES? SO HERE'S A
LITTLE BIT FROM THE PAPER WE
WROTE A REALLY LONG TIME AGO
AND PAYMENT.
BASICALLY WHAT WE DID WAS WE
TRIED TO DIVIDED INTO FIVE
TYPES OF PAYMENT. REIMBURSEMENT
FOR EXPENSES. COMPENSATION FOR
BURDENS, RISKS, INJURY.
APPRECIATION PAYMENT.
INCENTIVES TO GET PEOPLE TO
ENROLL AND GET THEM TO CONTINUE
TO PARTICIPATE. AND ALSO
PROFIT-SHARING.
SO I'M GOING TO GO THROUGH
THESE QUICKLY. THE REASON I
HAVE THIS TYPOLOGY, IS THAT I
AM TRYING TO CONVINCE YOU THAT
THE ETHICAL CONSIDERATIONS VARY
GREATLY DEPENDING ON WHICH OF
THESE TYPES OF PAYMENT YOU'RE
CONSIDERING.
I'M GOING TO START FIRST WITH
THE LAST ONE, MINIMAL BRACKET
THAT AND PUT IT ASIDE. THIS IS
WHERE MY VIEWS REALLY DIVERT
FROM A LOT OF OTHER PEOPLE. I
THINK WE REALLY NEED TO THINK
MORE SERIOUSLY ABOUT
PROFIT-SHARING.
I THINK WE ALL AGREE THAT
EXPLOITATION IS A SERIOUS
CONCERN. CLINICAL RESEARCH. WE
NEED TO AVOID IT PARTICULARLY
IN THE CONTEXT WHERE PEOPLE ARE
MAKING AN AWFUL LOT OF MONEY
OFF OF A TRIAL. FOR HIS ABOUT
EXPECTATIONS THAT IF
PARTICIPANTS DON'T SHARE IN
THOSE PROFITS AT ALL.
AND I KNOW PEOPLE WHO SEE
ETHICS GOING AROUND-- A LITTLE
PLUG FOR THE ETHICS GROUND
ROUNDS, WE DO THEN FOUR TIMES A
YEAR, AND TWO YEARS AGO WITH A
SESSION ON PROFIT SHARING FOR
SAMPLE DONORS. I WAS TRYING TO
ARGUE THAT WE SHOULD AT LEAST
CONSIDER IT IN SOME CASES.
SO WE COULD TALK ABOUT IT MORE.
BUT THAT IS DEFINITELY A FAIRLY
IDIOSYNCRATIC VIEW ON MY PART.
FOR THE REST I'M GOING TO SET
IT ASIDE, AND TALK ABOUT THE
OTHER FOUR TYPES.
SO REIMBURSEMENT COMPENSATION.
WHAT REIMBURSEMENT COMPENSATION
DO IS THEY REMOVE BARRIERS TO
RESEARCH ENROLLMENT. AND ALSO
OBVIOUSLY TO RESEARCH
PARTICIPATION. SO THEY ADDRESS
THE COSTS OF GETTING THERE, AND
THE BURDENS AND INJURIES THAT
THE PERSON HAS EXPERIENCE
ALTHOUGH WE KNOW US REGULATIONS
ARE NOT VERY GOOD ABOUT
COMPENSATING PARTICIPANTS FOR
INJURIES. OTHER COUNTRIES ARE
BETTER.
RESEARCH SUBJECTS SHOULD NOT BE
THE ONES TO BEAR THE COSTS TO
CONTRIBUTE TO THE SOCIAL GOOD.
THE SPECIFIC INDIVIDUAL SHOULD
NOT BE THE ONE WHO BEARS THE
COST OF IT. THEY SHOULD NOT BE
THE ONES WHO HAVE TO PAY TO GET
TO THE SITE, OR THE ONES WHO
HAVE TO PAY FOR CLINICAL CARE
IF THEY ARE INJURED AS A RESULT
OF BEING IN THE STUDY.
SO THAT SUGGESTS AN ARGUMENT TO
BE MADE WHICH I WILL MENTION
HERE. AND THEN WE CAN TALK
ABOUT IT MORE, IF PEOPLE WANT
TO HEAR LITTLE BIT MORE OF THE
ARGUMENT. REIMBURSEMENT
COMPENSATION NOT ONLY ARE THEY
ETHICALLY OKAY BUT ETHICALLY
OBLIGATORY IN SOME CASES THE
SENSE THAT IT WOULD BE
ETHICALLY IMPROPER NOT TO OFFER
THEM. THAT GETS US TO
REIMBURSEMENT COMPENSATION. I
HAVE SET PROFIT SHARING A PART.
AN APPRECIATION AND INCENTIVES
BOTH CAN BE LUMPED TOGETHER.
APPRECIATION PAYMENTS ARE
ESSENTIALLY SMALL PAYMENT ABOVE
AND BEYOND THE COSTS THAT CAN
ACT AS AN INTENSIVE.
SO THE WORRY IS, WE HAVE
REASONABLE DATA TO SHOW THIS.
REMOVING BARRIERS TO MAKE
PARTICIPATION COST NEUTRAL FOR
PEOPLE, FREQUENTLY DOES NOT
YIELD SUFFICIENT ENROLLMENT.
REMEMBER WE ARE TALKING ABOUT
STUDIES THAT SATISFY THE
ETHICAL REQUIREMENTS AND THE
REVELATORY REQUIREMENTS. ONE
OF THOSE IN MY VIEW THAT IS
MOST IMPORTANCE I MENTIONED IS
THAT THE STUDY HAS IMPORTANT
SOCIAL VALUE.
IF HE DOES HAVE IMPORTANT
SOCIAL VALUE, THAT GIVES
ETHICAL REASONS IN FAVOR OF THE
RESEARCH. ETHICAL REASONS TO
DO THE RESEARCH, TO GET PEOPLE
ENROLLED IN THE RESEARCH, TO
GET THEM THROUGH THE RESEARCH
AND TO REALIZE THE PRIMARY
GOALS OF THE RESEARCH.
AND SO WHAT THAT MEANS, IF WE
ARE IN A CONTEXT WHERE WE ARE
NOT GETTING ENOUGH PEOPLE
SIMPLY BY REMOVING THE
BARRIERS, THEN THERE IS
ACTUALLY A POSITIVE, ETHICAL
REASON TO CONSIDERING
INCENTIVES TO THE EXTENT THAT
IT WILL HELP PROMOTE THE GOAL
OF GETTING THE STUDY COMPLETED.
SO, THERE IS AN ETHICAL REASON
TO DO THAT. THERE IS AN
ARGUMENT FOR THAT. OBVIOUSLY
THERE ARE STILL CONCERNS. IN
PEDIATRIC RESEARCH, IS WHERE I
THINK THE BIGGEST CONCERN IS.
BECAUSE HERE WE HAVE A
SITUATION WHERE PAYMENT BEYOND
COSTS RAISES THE POSSIBILITY
FOR PARENTS TO MAKE MONEY OFF
OF CHILDREN'S ENROLLMENT.
ALMOST EVERYBODY'S GOING TO
AGREE. THAT IS ETHICALLY
PROBLEMATIC FOR PARENTS MAKING
MONEY BY ENROLLMENT THEIR
CHILDREN IN RESEARCH.
A COUPLE OF THINGS TO SAY ABOUT
THAT WORRY. ONE IS AGAIN TO
REMIND YOU, ASSUMING THAT THE
RESEARCH IS ETHICALLY
APPROPRIATE, AND IF THAT IS
TRUE, THEN EVEN IF THE PARENTS
ARE ENROLLING THEM TO MAKE THE
MONEY, THEY ARE HOPEFULLY
UNROLLING THE CHILDREN
SOMETHING THAT IS APPROPRIATE.
IN AN APPROPRIATE ACTIVITY.
THAT ADDRESSES SOME OF THE
WORRY.
AND FROM WHAT WE KNOW OF HIM
PSYCHOLOGY, EVEN SMALL
INCENTIVES, THE CHANCES IMPROVE
TO GET THE PARENTS TO ENROLL.
IF THEY HAVE SPECIFIC REASON
THAT A TRIAL IS PARTICULARLY
INAPPROPRIATE FOR THE CHILDREN,
IT WILL GIVE THEM LITTLE
INCENTIVE TO ENROLL THEIR
CHILDREN IN THE STUDIES. IF
THE INCENTIVES ARE RELATIVELY
SMALL. SO I THINK IN THE END,
THE SMALL INCENTIVES DOES NOT
RAISES SIGNIFICANT ETHICAL
CONCERNS. AND THIS IS
REFLECTED BY THE AMERICAN
ACADEMY OF PEDIATRICS. AND THEY
HAVE SOME GUIDANCE ON THIS.
THE MOST RECENT ONES I COULD
FIND-- I WILL BE INTERESTED TO
KNOW IF ANYBODY KNOWS MORE
RECENT ONES-- BUT THE MORE
RECENT ONES I COULD FIND WERE
FROM 2010. THE EARLIER ONES
FROM 1995, DESCRIBED THIS AS A
TOKEN PAYMENT. AND MORE RECENT
ONES DESCRIBE THIS IS A MINIMAL
PAYMENT. TOKEN SEEMS TO ME LIKE
ALMOST NO AMOUNT OF MONEY AT
ALL. MINIMAL MAYBE IS AT LEAST
A LITTLE BIT BETTER IN THAT
REGARD.
SO WHAT CAN IRBS DO IN THESE
CASES TO MAKE SURE THIS
CONCERNS ARE ADDRESSED? THE
FIRST IS TO MAKE SURE THE
RESEARCH IS APPROPRIATE AND
VALUABLE, AND THAT THE RISKS
ARE ADDRESSED AND YOU HAVE THE
RIGHT PROTECTIONS IN PLACE, AND
YOU MINIMIZE THE EXTENT TO
WHICH YOU CONDUCT THE RESEARCH
IN AN APPROPRIATE WAY. AND
MAKE SURE YOU ARE GETTING
ASSENT AND LOOKING AFTER KIDS'
DISSENT. IF YOU DOING THOSE
THINGS, LIES SOME INCENTIVES TO
PARENTS CAN BE ACCEPTABLE. AS I
SAID EARLIER WITHIN THE CONTEXT
OF MAKING SURE YOU ARE THINKING
ABOUT THE POSSIBILITY THAT
THERE MIGHT BE IDIOSYNCRATIC
RISKS OR CONCERNS FOR
PARTICULAR CHILDREN.
IN THEIR MEDICAL IDIOSYNCRATIC
RISKS, MAYBE A CLINICIAN SHOULD
EVALUATE THE CHILD. IF THERE
ARE MORE OBJECTIONS TO THE
RESEARCH THAT COULD BE A REASON
FOR SOMEBODY TO MEET WITH THE
CHILD INDEPENDENTLY OF THE
PARENTS, JUST TO MAKE SURE THAT
THEY ARE COMPARABLE AND WILLING
TO BE PART OF THE STUDY, IF
THERE ARE WORRIES THAT THEIR
AGREEMENT OR LACK OF ASSENT IS
NOT GOING TO BE SUFFICIENT. OR
IF THEY ARE NOT GOING TO
EXPRESS CONCERNS IN THE
PRESENCE OF THEIR PARENTS.
AND THE LAST THING AND THIS
MIGHT BE SOMETHING WORTH
TALKING ABOUT. IF THE INCENTIVE
TO THE PARENTS A RELATIVELY
SMALL, THAT DOESN'T CUT OFF ALL
CHANCES FOR THE PARENTS TO MAKE
MONEY. THE OTHER WAY THAT
COULD HAPPEN IS IF THEY DIVERT
SOME OF THE PAYMENTS THAT ARE
SUPPOSED TO GO TO THE MINORS.
AND OF THE PARENTS TAKE OVER
THOSE PAYMENTS.
AND SO THERE ARE VARIOUS WAYS
TO THINK ABOUT TRYING TO COME
UP WITH MECHANISMS TO ENSURE
PAYMENTS WHICH ARE INTENDED FOR
MINORS. THAT THEY GO TO
MINORS. ONE OF THE THINGS THAT
SOME PEOPLE USE IS GIFT CARDS
TO CERTAIN STORES FOR INSTANCE
THAT MINORS WOULD BE MORE
INTERESTED IN THAN PARENTS.
THAT IS AT LEAST ONE
POSSIBILITY.
ALL RIGHT. A SUMMARY. STILL
LIVING A LOT OF TIME FOR
DISCUSSION AND SEEING WHAT
EVERYBODY IS INTERESTED IN, AND
WANT TO TALK ABOUT. QUICK
SUMMARY.
HOPEFULLY WE ALL AGREE THAT
PEDIATRIC RESEARCH AT LEAST IN
GENERAL HAS IMPORTANT SOCIAL
VALUE. NOW AGAIN, THE CHALLENGE
FOR IRBS IS TO MAKE SURE THAT
THE STUDIES, THE INDIVIDUAL
STUDIES THAT WE APPROVE
ACTUALLY HAVE IMPORTANT SOCIAL
VALUE. NOT ENOUGH THAT IN
GENERAL, OR IN THE AGGREGATE OF
PEDIATRIC RESEARCH, HAS
IMPORTANT SOCIAL VALUE. WE
WANT TO MAKE SURE THAT THE
INDIVIDUAL STUDIES WE APPROVE,
INDIVIDUAL STUDIES WE CONDUCT,
INDIVIDUAL STUDIES WE ENROLL
CHILDREN IN HAVE IMPORTANT
SOCIAL VALUE.
AND THEY OBVIOUSLY RAISE
IMPORTANT ETHICAL CONCERNS AND
I THINK THAT THE INVOLVEMENT OF
ONE CAREFUL IRB EVALUATION AND
REVIEW AND INVOLVEMENT OF
ETHICALLY CONCERNED RESEARCHERS
TO OFFER A WAY DOES PERMIT
VALUABLE RESEARCH WHILE
ADDRESSING THE ETHICAL
CONCERNS. LOOK FORWARD TO YOUR
QUESTIONS AND COMMENTS.
>> PEG: THANK YOU VERY MUCH.
ANYBODY THAT HAS QUESTIONS
PLEASE GO AHEAD AND SUBMIT THEM
BY CLICKING ON THE BOX BELOW
THE VIDEO TITLED "LIVE
FEEDBACK." WE HAVE ONE COMMENT
OR QUESTION HERE.
THIS IS ABOUT ASSENT. THIS
INDIVIDUAL SAYS, HOW ABOUT A
MIXED APPROACH? FOLLOW THE
STEPS PRESENTED IN YOUR TALK.
GIVE INFORMATION TO ALL. ASK IF
THERE ARE QUESTIONS. SET AN AGE
OVER WHICH ASSENT IS A MUST,
12-14 AS SUGGESTED. BUT ALSO
HAVE A TRANSITION AGE SAY 8-12,
IN WHICH PARENTS ARE ASKED IF
THEY WANT THEIR CHILD TO GIVE
ASSENT.
>> DR. WENDLER: HMM.
INTERESTING. I HAVE GIVEN THIS
TALK A LOT OF TIMES AND I DO
NOT THINK I HAVE HEARD THAT
QUESTION BEFORE.
I GUESS, WITH THE IDEA BE ...
SO WOULD THE SUGGESTION BE YOU
ASK THE PARENTS, DO THEY THINK
THAT FOR THEIR CHILD, THEIR
CHILD ISN'T PARTICULARLY MATURE
OR SAVVY OR SOMETHING LIKE
THAT? THEY DON'T THINK IT'S
APPROPRIATE FOR THEM? OR THE
PARENTS JUST WANT THEM TO?
WHAT I WOULD SAY IS, MY
INCLINATION IS ... LET ME WRITE
THE QUESTION AND RESPOND BACK
TO THIS. I WOULD BE INCLINED
TO LEAVE THE ASSENT AT 12-14.
BUT AGAIN YOU GIVE INFORMATION
TO THE YOUNGER CHILDREN. YOU
TALK TO THEM. YOU GET THERE
VIEWS. AND AT A MINIMUM YOU
ENSURE THAT YOU ARE NOT
OBJECTING. AT LEAST YOU ARE
ENGAGING WITH THEM TO THAT
EXTENT. I WOULD DEFINITELY WANT
TO DO THAT.
ONE THING I WOULD SAY IS IF YOU
WANT TO GO BEYOND THAT TO SAY,
WE ARE GOING TO REQUIRE THEIR
ACTUAL AFFIRMATIVE AGREEMENT,
THE ONE THING I WORRY ABOUT IS
THAT THERE ARE SOME GUIDELINES
WHICH SAY WHAT YOU DO IS FOR
YOUNGER CHILDREN, YOU ASKED
WHETHER THEY ASSENT. YOU GIVE
THEM THIS INFORMATION AS I
SUGGESTED AND THEN YOU ASK IF
THEY AGREE AND IF THEY ASSENT.
AND THEN YOU GET THE ANSWER. IF
THEY SAY YES, THEY ARE IN THE
STUDY. IF THEY SAY NO, YOU TAKE
THAT INTO CONSIDERATION IN
DECIDING WHETHER OR NOT TO
ENROLL THEM.
AND THAT STRIKES ME AS A REALLY
BAD IDEA. I DON'T THINK WE
SHOULD BE POSITIVELY ASKING
MINORS, DO YOU WANT TO BE IN
THE STUDY? UNLESS WE'RE GOING
TO TAKE A "NO" AS A NO.
>> PEG: I IMAGINE, YOUR BIO
ETHICS COUNCIL MAY RUN INTO A
SIMILAR SITUATION WHERE YOU
HAVE A PROTOCOL THAT HAS
POTENTIAL FOR DIRECT BENEFIT,
SAY IN A POPULATION OF SICK
CHILDREN. AND THE INDIVIDUAL
PARENTS PROVIDE PERMISSION.
THE CHILD ASSENTS. AND AS THEY
GET INTO THE STUDY IT BECOMES
APPARENT THAT THE CHILD JUST
DOES NOT WANT TO CONTINUE IN
THE STUDY. SO WHEN YOU'RE FACED
WITH THAT, HOW DO YOU DEAL WITH
IT?
>> DR. WENDLER: SO THOSE ARE
REALLY INTERESTING CASES. THE
FIRST THING TO SAY ABOUT THAT
IS, MAYBE EVERYBODY KNOWS, BUT
A REMINDER THAT EVEN THOUGH
THERE IS THIS ASSENT
REQUIREMENT THE REGULATIONS
HAVE A PROVISO FOR WAVING IT,
IF THERE IS INSUFFICIENT CHANCE
FOR IMPORTANT POTENTIAL BENEFIT
FOR THE CHILDREN.
SO THAT IS ANOTHER CASE WHERE I
THINK THAT ASKING FOR
PERMISSION IS APPROPRIATE ONLY
IF YOU ARE GOING TO ACCEPT THE
"NO." IF THIS IS A POTENTIALLY
LIFE-SAVING PROTOCOL FOR CHILD,
AND ON THAT BASIS THE DECISION
HAS BEEN MADE, THAT YOU ARE
GOING TO NOT REQUIRE ASSENT
BEEN IN DECADES YOU SHOULD NOT
ASK THE CHILD FOR THEIR ASSENT.
YOU GIVE THEM ALL THE
INFORMATION AND YOU SAY, HERE
IS WHAT WE ARE PLANNING TO DO.
ANYTHING ASKING FOR ASSENT, YOU
GET A NO, AND THEN YOU TALK
ABOUT IT MORE AND HAVE THE
PARENTS DECIDE CAN BE A REALLY
BAD PROCESS. BUT WE DO GET
COUNCILS WHERE THE CHILD GETS
ENROLLED. THEY ARE NOW IN THE
MIDST OF A PROTOCOL AND THEY
START OBJECTING AND THEY WANT
OUT. THOSE ARE REALLY
INTERESTING, HEART CASES AND I
THINK CALLING A COUNCIL IS THE
RIGHT THING TO DO IN THOSE
CASES BECAUSE IT IS REALLY THE
ONLY WAY YOU CAN ASSESS THEM
AND GIVE RIGHT GUIDANCE TO KNOW
WHAT THE CIRCUMSTANCES ARE.
SO FOR A FULL OUT ONE OF THESE
EXAMPLES. I USE THIS IS AN
ARGUMENT. ONE OF THE COUNCILS
WE HAD AROUND ASSENT, PROBABLY
ABOUT 10 YEARS AGO, WE HAD A...
THIS ALSO BRINGS OUT ASSENT AND
COMPENSATION IN A WAY THAT IS
INTERESTING, THIS WAS A CASE OF
A KID WHO WAS NINE. WHO HAD A
VERY RARE NIH-TYPE DISEASE.
THEY HAD BEEN IN A NUMBER OF
STUDIES. HAD A LOT OF CLINICAL
CARE. AND THEY HAD A VERY RARE
VERSION OF THEIR DISEASE, WHICH
HAD NOT BEEN SEEN VERY OFTEN.
THE INVESTIGATORS THOUGHT IF
THEY COULD GET SOME BLOOD
THROUGH A REESE'S PROCEDURE
(SOUNDS LIKE) THEY MIGHT LEARN
MORE ABOUT THIS DISEASE ITSELF.
IN THAT CASE, THE IRB DECIDED
TO STIMULATE THAT THEY HAD TO
GET THE ASSENT BECAUSE IT WAS
NO PROSPECT OF DIRECT BENEFIT.
PURELY RESEARCH FOR REESE'S.
PRETTY STANDARD. THE PARENTS
WERE VERY SUPPORTIVE OF THE
RESEARCH ON THE DISEASE. THE
STIPULATED AND ETHICS COUNCIL.
SO I WENT UP AND TALK TO THIS
NINE-YEAR-OLD. HE WAS VERY
SMART, SAVVY. HE KNEW A LOT
ABOUT MEDICINE. I EXPLAINED
EVERYTHING TO HIM. AND THEN I
ASKED HIM. DO YOU WANT TO GO
THROUGH THIS PROCEDURE? HE SAID
NO. AND I ASKED WHY NOT. HE
JUST SAID, THERE'S A BASKET OR
HOOP ON THE END OF HIS FLOOR.
HE HAD A COUPLE OF BUDDIES.
THEY LIKE PLAYING BASKETBALL.
AND HE WENT DOWN FOR REESE'S
FOR 20 MINUTES, THAT WILL BE 20
MINUTES LESS PLAYTIME FOR HIM.
A REALLY REASONABLE DECISION
FOR NINE-YEAR-OLD WHO DOES NOT
UNDERSTAND WHAT HE COULD
CONTRIBUTE. BUT I THINK IT WAS
A MISTAKE TO LEAVE THAT
DECISION UP TO THAT
NINE-YEAR-OLD.
AND I THINK IF WE JUST
PRESENTED WHAT WE WERE DOING,
WE WOULD'VE GOTTEN THROUGH IT
ABSOLUTELY FINE. ANOTHER
THING, JUST TO GIVE
COMPENSATION ON THIS. I
ACTUALLY TALKED TO THAT CHILD
TWICE. HE WAS ADAMANT. HE WAS
NOT GOING TO DO IT.
AS I WAS LEAVING THE SECOND
TIME, I WALKED DOWN THE
HALLWAY. I PASSED HIS MOTHER.
HIS MOTHER WAS DISAPPOINTED BUT
SHE ACCEPTED HER SON'S DECISION
GIVEN THAT ASSENT WAS BEING
REQUIRED AND I SAID TO HER, BY
THE WAY WHAT DO YOU THINK WE
OFFERED $10? AND SHE SAID HE
WOULD ABSOLUTELY DONE IT IN A
HEARTBEAT.
SOWA QUESTION FOR THE AUDIENCE,
WHETHER OR NOT THAT WILL BE
ETHICALLY ACCEPTABLE TO OFFER
HIM $10. I THINK IT WOULD'VE
BEEN.
>> PEG: I DON'T THINK WE HAVE
ANY OTHER QUESTIONS.
DOES ANYONE ELSE HAVE ANYTHING
THEY WANT TO SUBMIT GO AHEAD.
BUT I DON'T SEE ANYTHING ELSE.
>> DR. WENDLER: GREAT.
>> PEG: THANK YOU VERY MUCH AND
I DO WANT TO PUT IN A PLUG.
CHRISTIAN READY CHIEF OF YOUR
BIOETHICS APARTMENT THE
PRESENTATION EARLIER THIS YEAR
ON COMPENSATION. AND YOU
ALLUDED TO YOUR DEPARTMENT'S
DISCUSSION ABOUT COMPENSATION
AND THOUGHTS ON IT. FOR PEOPLE
THAT ARE INTERESTED MORE ON
THAT TOPIC, I WOULD SUGGEST
THEY LOOK AT THAT. JANUARY
SESSION FROM THIS YEAR.
>> DR. WENDLER: CHRISTINE IS
ONE OF THE TRUE EXPERTS ON THE
ETHICS OF COMPENSATION
RESEARCH.
>> PEG: SHE WAS KIND ENOUGH TO
SHARE HER THOUGHTS WITH US.
>> DR. WENDLER: GREAT.
>> PEG: WE APPRECIATE YOU
JOINING US TODAY DR. WENDLER.
>> DR. WENDLER: THANKS PEG. 1365 00:45:24,321 BYE-BYE.