GOOD MORNING AND WELCOME TO
THE 2023 ETHICAL AND REGULATORY
ASPECTS RESEARCH.
I THINK IT'S THE 25th YEAR WE'VE
OFFERED THE COURSE AND HAPPY TO
BE HERE WITHOUT A MASK TODAY.
I'M GOING TO FIRST INTRODUCE
MYSELF AND GO THROUGH
INTRODUCTORY REMARKS AND MOVE ON
TO CONTENT.
YOU'LL SEE THIS FROM A NUMBER OF
US.
I AM SPEAKING FOR MYSELF.
I'M NOT EXPRESSING THE VIEWS OF
NIH, HHS OR THE U.S. GOVERNMENT.
SO THESE ARE THE COURSE
OBJECTIVES.
I'M NOT GOING READ THROUGH THEM.
THEY'RE ON THE SYLLABUS AND IN
THE DOCUMENTS ON CANVAS WHICH
I'LL SAY A LITTLE MORE ABOUT BUT
THE BOTTOM LINE IS WE WANT TO
GIVE YOU BOTH SUBSTANCE,
KNOWLEDGE AND SOME SKILLS TO
APPLY WHAT YOU LEARNED HERE TO
YOUR WORK, YOUR RESEARCH,
WHATEVER IT IS THAT YOU PLAN TO
USE THIS INFORMATION FOR.
SO HERE'S A QUICK OVERVIEW OF
THE COURSE.
TODAY'S THE FIRST OF SEVEN WEEKS
AND WE'RE GOING TO DO SOME
BASICS TODAY THEN NEXT WEEK
WE'RE GOING TO TRANSITION TO
ISSUES AROUND INFORMED CONSENT
FOLLOWED BY STUDY DESIGN, A DAY
DEDICATED TO GENETICS WITH SOME
OF THE UNIQUE ASPECTS OF GENETIC
RESEARCH AND HAVE EQUITY AND
SUBJECT SELECTION AND HAVE AN
INTERNATIONAL DAY AND THEN THE
LAST DAY IS ETHICS IN NOVEL
TECHNOLOGIES.
I'LL ALSO NOTE THE MAJORITY OF
THE FACULTY WILL BE FROM THE NIH
DEPARTMENT HERE OF BIOETHICS AND
THE CLINICAL CENTER REALIZING I
FORGOT TO INTRODUCE MYSELF.
I'M HOLLY TAYLOR ON THE FACULTY
IN THE DEPARTMENT AND I'LL BE
THE EMCEE FOR THE WHOLE COURSE
SO YOU'LL SEE A LOT OF ME BOTH
INTRODUCING FOLKS AND GIVING A
NUMBER OF LECTURES.
A COUPLE ADMINISTRATIVE DETAILS,
IF YOU'RE VIEWING US THROUGH THE
LIVE VIDEO STREAM BUT HAVEN'T
YET REGISTERED OR ENROLLED AND
REGISTERED IN THE COURSE AND
YOU'D LIKE TO, THERE'S -- YOU
CAN SELF-ENROLL.
WE'VE SENT OUT INFORMATION ON
HOW TO DO THAT.
WE'LL DO THAT AGAIN AFTER
TODAY'S SESSION.
IF YOU SELF-ENROLL YOU'LL HAVE
ACCESS TO ALL THE MATERIALS AND
IF YOU WANT ACCESS TO ALL THE
LECTURES THAT'S THE PLACE TO GO.
THERE'S A SELF-REGISTRATION FORM
AND WE NEED TO YOU COMPLETE THAT
IF YOU WANT TO GET A CERTIFICATE
OF COMPLETION.
THE WAY WE KEEP TRACK OF WHETHER
YOU PARTICIPATED OR VIEWED A
LECTURE LIVE OR A RECORDING IS
WE ASK YOU TO COMPLETE A SESSION
QUIZ THAT IS ON CANVAS AND ONE
OTHER REASONS TO GO TO THE
CERTIFICATE.
THERE'S GOING TO BE A WORD OF
THE DAY AND TWO QUESTIONS YOU'LL
NEED TO COMPLETE.
THE WORD FOR TODAY IS BELMONT.
YOU'LL LEARN A LITTLE BIT MORE
ABOUT WHAT BELMONT IS, THE
BELMONT REPORT AND EACH DAY
WE'LL GIVE YOU A WORD OF THE DAY
AND WE'LL TRY TO WORK IT IN A
COUPLE TIMES BUT DON'T PANIC
ABOUT THE WORD OF THE DAY.
THESE QUIZZES AREN'T RATED.
IT'S REALLY JUST TO LET US KNOW
YOU'RE OUT THERE AND VIEWING.
AND THERE'S A SESSION TO LET US
KNOW WHETHER WE MET THE
OBJECTIVES WE MET FOR OURSELVES
FOR EACH OF THE SESSIONS AND
CONNOR WHO IS HERE IN LIPSETT
WILL SEND THAT TO YOU.
IT'S A QUICK EVALUATION TO GIVE
US FEEDBACK ON OUR LECTURES.
I'VE SENT AN ASSESSMENT TO
EVERYONE WHO ENROLLED IN THE
COURSE.
I'LL RESEND THAT TODAY.
THERE'S ABOUT 850 OF YOU THINK
PRE SELF-REGISTERED IN THE
COURSE AND IF ALL OF YOU COULD
TAKE IT THAT'D BE GREAT.
ABOUT 250 HAVE TAKEN IT SO FAR
EVEN THOUGH YOU LISTEN TO
TODAY'S LECTURE I'LL LEAVE IT
OPEN TO SEE IF WE GET ADDITIONAL
RESPONSES.
I'M JUST GOING TO WALK THROUGH
WHAT THE CANVAS HUB WILL LOOK
LIKE FOR YOU.
SO WHEN YOU LOG INTO THE COURSE
WEBSITE, THIS IS WHAT YOU'LL
SEE.
THERE'S KEY DOCUMENTS AT THE
TOP.
THE SELF-REGISTRATION FORM IS
LINKED AT THE TOP.
THERE'S COURSE BASICS.
THE SYLLABUS WHICH IS ACTUALLY
NOW I TOOK IT IT'S FINAL AND
POSTED THERE.
AND A COUPLE OF OTHER KEY
DOCUMENTS INCLUDING MY BIO AS
WELL AS WITH THE FACULTY YOU'LL
HEAR FROM.
THERE'S A LINK TO THE
SELF-REGISTRATION TO THE RIGHT
OF THE SCREEN.
YOU CAN CLICK THERE OR THERE TO
SELF-REGISTER.
THIS IS WHAT YOU'LL SEE AND
THEY'LL GET INFORMATION FROM YOU
HOW YOU'D LIKE TO SEE YOUR NAME
ON THE CERTIFICATE AND THINGS
LIKE THAT.
THE OTHER THING I WANT TO POINT
OUT IS FOR EACH SESSION THERE'S
ON THE CANVAS HUB IT'S CALLED A
MODULE.
THIS IS SESSION 1.
THAT CIRCLE IS SUPPOSED TO BE ON
THE TOP DOCUMENT THERE BUT
THERE'S A SUMMARY OF EACH
SESSION THERE, LINKS TO THE
TEXTBOOKS.
THERE'S ALSO INFORMATION THERE,
THE POWER POINT SLIDES FOR ALL
THE PRESENTATIONS ARE POSTED AT
8:00 A.M. ON THE DAY OF CLASS.
IF YOU OPEN THIS UP TODAY, THOSE
ARE THE FIRST THINGS YOU'LL SEE
THE POWER POINTS FOR EACH OF THE
PRESENTATIONS.
THIS IS WHAT OUR SESSION LOOKS
LIKE.
EACH THE SESSION SUMMARIES LOOKS
LIKE.
THERE'S THE OBJECTIVES FOR THAT
SESSION, A SCHEDULE AND THE
READINGS AND AS I MENTIONED THE
POWER POINTS WILL BE POSTED.
THEY'RE POSTED NOW.
IF YOU WANT TO ACCESS THOSE
FOLLOW ALONG.
THERE'S ACCESS TO THE READINGS
AND YOU CAN CLICK ON THEM AND
IT WILL TAKE YOU ONLINE AND AS
OF TODAY THERE ARE ABOUT 10 OF
US PHYSICALLY HERE IN LIPSETT.
FOR THOSE OF US ON CAMPUS AT THE
NIH, FEEL FREE NEXT WEEK TO COME
AND BE HERE IN PERSON OR JUST
DROP IN SESSION 4, SESSION 3,
WHATEVER, THAT'D BE GREAT.
SO IF YOU'RE HERE YOU GET
PRIORITY IN TERMS OF ASKING
QUESTIONS SO THAT'S ONE THING
THAT IS IN FAVOR OF COMING.
BUT BECAUSE THE VAST MAJORITY OF
YOU ARE ONLINE, WE HAVE A COUPLE
OF WAYS FOR YOU TO GET QUESTIONS
TO ME AND TO CONNOR AFTER EACH
SESSION SO AFTER EACH LECTURE
THERE'S TIME SET ASIDE FOR
DISCUSSION.
ONE WAY TO POSE A QUESTION IS TO
GO TO THE DISCUSSION BOARD IN
CANVAS AND THERE'S A PLACE THAT
POSE QUESTIONS FOR SESSION 1
HERE.
POSE YOUR QUESTION THERE.
I'LL HAVE IT AT MY LAPTOP.
YOU CAN ALSO SEND AN E-MAIL TO
MISS -- THIS E-MAIL AND CONNOR
WILL GET IT TO US.
SO IF WE DON'T HAVE A CHANCE TO
ANSWER THOSE QUESTIONS IN REAL
TIME, IF YOU SEND IT BY E-MAIL I
POST IT FOR YOU IN THE
DISCUSSION BOARD AND ANSWER THE
QUESTIONS THERE.
IF I CAN'T ANSWER IT AND IT'S
SOMETHING THAT SOMEONE ELSE
COVERED, I'LL REACH OUT TO THEM
AND ASK THEM TO ANSWER THE
QUESTION.
SO I MENTIONED THE SESSION
QUIZZES.
IMPORTANT THING TO KEEP IN MIND
IF YOU WANT TO CERTIFICATE OF
COMPLETION, YOU HAVE TO COMPLETE
THREE OF THE SEVEN QUIZZES.
YOU CAN COMPLETE ALL OF THEM IF
YOU WANT BUT YOU HAVE TO
COMPLETE AT LEAST THREE.
IF YOU'RE AN NIH EMPLOYEE AND
CONTRACTOR AND WANT TO APPLY
THIS COURSE TOWARD THE CORE
CURRICULUM CREDIT AND A NURSE
AND WANT CEU CREDITS I KNOW
THERE'S ABOUT 50 FROM THE NIH
AND ANOTHER 25 WHO IDENTIFIED
YOU'RE INTERESTED IN GETTING THE
CERTIFICATE AS A NURSE OR NIH
EMPLOYEE, YOU HAVE TO TAKE AT
LEAST SIX OR SEVEN OF THOSE
QUIZZES.
AGAIN, SCORES DON'T MATTER.
I'M SAYING THIS BECAUSE I OFTEN
GET E-MAILS AFTER CLASS, PLEASE,
PLEASE HOLLY TELL ME THE WORD OF
THE DAY.
TODAY IT'S BELMONT AND IF YOU
DON'T HEAR IT, IT'S OKAY.
YOU CAN GUESS.
FINAL THING IS THIS IS WHERE THE
QUIZZES ARE.
THEY'RE UNDER THE TAB CALLED
QUIZ AND EACH SESSION OPENS AT
11:30 SO RIGHT AFTER CLASS YOU
CAN GO RIGHT TO THE SESSION QUIZ
AND COMPLETE IT.
THE QUIZZES ARE ALSO LINKED ON
THE MODULE PAGE GOING TO SESSION
1 YOU'LL SCROLL TO THE BOTTOM
AND SEE THE LINK TO THE QUIZ.
PLEASE SEND ME ADMINISTRATIVE
QUESTIONS YOU HAVE AND THERE'S A
LINK TO A DOCUMENT THAT SAYS
COURSE BASICS.
SO IF YOU HAVE A QUESTION ABOUT
SOME OF THE STUFF YOU'VE COVERED
THAT'S A PLACE -- I'VE COVERED
THAT'S A PLACE TO GO BUT I'M
HAPPY TO ANSWER QUESTIONS.
WE'LL GO TO CONTENT FOR SESSION
1.
WE'LL START THE DAY WITH A
FRAMEWORK.
THEN WE'LL HAVE A GUEST LECTURER
WHO IS GOING TO COME IN ON ZOOM
AND YOU'LL SEE ME AGAIN TALKING
ABOUT INSTITUTIONAL REVIEW
BOARDS.
IT'S MY GREAT PLEASURE TO
INTRODUCE DR. CHRISTINE GRADY
THE CHIEF OF OUR DEPARTMENT HERE
OF BIOETHICS.
SHE'S A NURSE BY TRAINING ALSO
HAS A Ph.D. IN PHILOSOPHY, DOES
A TON OF EMPIRICAL AND
CONCEPTUAL WORK AROUND INFORMED
CONSENT, STUDY DESIGN, RESEARCH
ETHICS AND RECENTLY WORK AROUND
MORAL DISTRESS THAT HEALTH CARE
PROVIDERS EXPERIENCE ESPECIALLY
POST COVID.
SHE'S BEEN WITH THE DEPARTMENT
FOR A VERY LONG TIME.
SHE TAUGHT THIS COURSE FOR THE
FIRST 20 PLUS YEARS AND IT'S MY
GREAT PLEASURE TO HAND IT OVER
TO HER FOR THE FRAMEWORK WE'RE
GOING TO USE YOU'LL HEAR ABOUT
THROUGHOUT THE COURSE.
>> THANK YOU, HOLLY.
YES, I'VE BEEN AROUND A LONG
TIME.
THIS COURSE I'VE BEEN DOING MANY
YEARS.
I HAVE THE PLEASURE -- FIRST,
GOOD MORNING TO EVERYBODY HERE.
IT'S NICE TO SEE FACES HERE AND
EVERYONE ONLINE.
GOOD MORNING TO YOU, TOO.
I'LL SET UP THE FRAMEWORK FOR
THE ETHICAL CONDUCT OF RESEARCH
AND THAT'S WHAT I'M GOING TO DO.
I HAVE THE SAME DISCLAIMER AS
WELL AS I HAVE NO CONFLICTS TO
DECLARE.
I WANT TO START BY PROPOSING THE
TWO QUESTIONS WE NEED TO ASK
FROM AN ETHICAL PERSPECTIVE
ABOUT CLINICAL RESEARCH ARE
SHOULD WE DO IT, NUMBER ONE AND
IF SO, HOW SHOULD WE DO IT.
I SHOULD START BY SAYING WHAT IS
CLINICAL RESEARCH.
CLINICAL RESEARCH IS RESEARCH
WITH HUMANS MOST OF THE TIME AND
CERTAINLY IN OUR WORLD RELATED
TO HEALTH.
BUT NOT ALWAYS.
SO SHOULD WE DO IT?
WELL, ONE THING IS CLINICAL
RESEARCH HAS RESULTED IN
COMPELLING SOCIETAL HEALTH
BENEFITS.
CERTAINLY THINGS LIKE NEW
THERAPIES, DIAGNOSTIC AND
PREVENTIVE STRATEGIES, IMPROVING
THE QUALITY OF LIFE AND
UNDERSTANDING THE PATH OF
DISEASE.
THERE'S A LOT OF GOOD EXAMPLES
WE CAN TALK ABOUT.
ONE RECENT ONE, COVID VACCINES.
CLINICAL RESEARCH, DEVELOPED,
FOUND HOW TO MAKE THE VACCINES,
DEVELOP THE VACCINES AND THEN
THE VACCINES SAVED MANY PEOPLE'S
LIVES.
HIV THERAPIES.
I STARTED MY CLINICAL WORK MANY
YEARS AGO IN HIV WHEN IT WAS A
UNIFORMLY FATAL DISEASE AND NOW
IT'S A CHRONIC DISEASE THAT
THANKS TO THE RESEARCH THAT
DEVELOPED THERAPIES PEOPLE LIVE
PRETTY NORMAL LIFE SPAN AND HAVE
A GOOD QUALITY OF LIFE.
STATINS ARE ANOTHER EXAMPLE THEY
REDUCE TRIGLYCERIDES AND
CHOLESTEROL IN THE BLOOD AND
HAVE HELPED MANY PEOPLE AVOID
HEART DISEASE.
THERE ARE OTHER VERY DRAMATIC
ONES.
IN THIS BUILDING THERE'S CHEMO
THERAPY FOR CHILDHOOD LEUKEMIA
WHICH USED TO BE FATAL AND NOW
HAS A 90% SURVIVAL RATE.
GET THE SENSE OF THE BENEFITS OF
DOING RESEARCH FOR SOCIETY FOR
THE HEALTH OF INDIVIDUALS IS
PRETTY GREAT.
THE SECOND BULLET HERE IS ABOUT
CLINICAL RESEARCH PROVIDES
EVIDENCE.
PROVIDES AN EVIDENCE BASE FOR
CLINICIANS.
WHEN YOU GO TO THE DOCTOR FOR
WHATEVER YOU GO TO THE DOCTOR
FOR YOU WANT THE DOCTOR TO HAVE
SOME EVIDENCE FOR HOW TO
DIAGNOSE YOU OR TREAT YOU.
THAT EVIDENCE SHOULD COME OR
OFTEN DOES COME FROM CLINICAL
RESEARCH.
I THINK IT'S ALSO INTERESTING TO
THINK ABOUT THE OTHER IMPACTS OF
RESEARCH.
THIS IS FROM FROM THE NIH WEB
PAGE.
IT DOES INCLUDE MORE THAN
CLINICAL RESEARCH BECAUSE NIH IS
ABOUT MORE THAN CLINICAL
RESEARCH.
YOU CAN SEE ON THE LEFT-HAND
SIDE OF THE SCREEN THERE
IMPROVING HEALTH IN THE WAYS I
JUST DESCRIBED REVOLUTIONIZING
SCIENCE AND SERVING SOCIETY.
I WANT TO SPEND A SECOND ON THE
SERVING SOCIETY PART.
RESEARCH HAS THESE OTHER
OUTCOMES THAT ARE ACTUALLY
PRETTY BENEFICIAL.
SOME ARE ECONOMIC.
THERE'S DATA ON THE DIRECT
ECONOMIC CONTRIBUTIONS OF
MEDICAL RESEARCH.
SOME OF IT IS SPURRING ECONOMIC
GROWTH, GIVING JOBS, CREATING
INDUSTRIES, THINGS LIKE THAT.
AND THEN THERE ARE SOCIETAL
BENEFITS OF IMPROVED HEALTH AND
OF IMPROVED RESEARCH.
PRODUCTIVITY OR UNDERSTANDING
HOW DIETARY GUIDELINES SHOULD BE
FORMED.
THOSE ARE THE KINDS OF THINGS
AND IF YOU'RE INTERESTED YOU CAN
GO TO THE WEBSITE.
IF I'VE CONVINCED YOU, RESEARCH
IS A GOOD THING.
THE QUESTION THEN IS, WHY IS IT
PROBLEMATIC ETHICALLY?
IT'S PROBLEMATIC ESSENTIALLY FOR
THIS REASON.
THE PRIMARY GOAL OF CLINICAL
RESEARCH IS TO GENERATE USEFUL
KNOWLEDGE.
USEFUL KNOWLEDGE ABOUT HUMAN
HEALTH AND ILLNESS BUT NOT TO
BENEFIT THE PARTICIPANTS IN THEY
OR NOT NECESSARILY TO BENEFIT
THE PARTICIPANTS IN STUDIES
THOUGH SOMETIMES THEY DO BENEFIT
DIRECTLY.
IF THAT'S RIGHT AND THE WAY
RESEARCH IS SET UP, THEN WE'RE
BASICALLY ASKING A SMALL NUMBER
OF PEOPLE TO ACCEPT A CERTAIN
AMOUNT OF RISK AND BURDEN AND
INCONVENIENCE IN ORDER TO LEARN
HOW TO BENEFIT OTHERS.
THEREFORE THERE'S MEANS TO
DEVELOPING USEFUL KNOWLEDGE AND
THE RISK OF BEING EXPLORATIVE
AND THIS IS COMMON WISDOM.
PEOPLE THINK OF CLINICAL
RESEARCH AS USING PEOPLE AS
GUINEA PIGS AND THERE'S
MISUNDERSTANDING HOW RESEARCH
GETS DONE AND HOW PEOPLE ARE
ENGAGED IN RESEARCH NOT
NECESSARILY AS HUMAN GUINEA
PIGS.
IT LEADS US TO THE DEMAND FOR
THE ETHICS IN CLINICAL RESEARCH
TO HAVE AT LEAST TWO PRONGS.
THE ETHIC OF CLINICAL RESEARCH
PROMOTES RESPONSIBLE AND USEFUL
RESEARCH THAT HAS THE
POSSIBILITY OF BENEFITING
SOCIETY WHILE WE'RE PROTECTING
MINIMIZING HARM TO MINIMIZING
THE POSSIBILITY OF EXPLOITATION
AND PROTECTING THE RIGHTS AND
WELFARE OF THE PARTICIPANTS THAT
WE'RE ENGAGED IN CLINICAL
RESEARCH.
THE ETHICS OF CLINICAL RESEARCH
REALLY HAS BOTH OF THESE
DEMANDS.
THERE ARE A NUMBER OUT THERE OF
ETHICAL REQUIREMENTS AND
GUIDANCE IN THE LITERATURE AND
REGULATIONS.
THERE ARE CODES OF ETHICS AND
THING LIKE THAT.
BASICALLY THESE ALL TRY TO DO
THOSE TWO THINGS.
THEY PROMOTE THE RESPONSIBLE
CONDUCT OF RESEARCH WHILE
SEEKING PROGRESS IN
UNDERSTANDING AND INTERVENING
HEALTH AND MINIMIZING
EXPLOITATION OF THE INDIVIDUALS
ENGAGED AND MAKE SURE THEIR
RIGHTS AND WELFARE ARE RESPECTED
WHILE CONTRIBUTING TO KNOWLEDGE
AND MAINTAIN PUBLIC TRUST IN THE
ENTERPRISE OF RESEARCH.
SO HOW DO WE THINK ABOUT HOW TO
DO A CLINICAL RESEARCH TO
PROMOTE USEFUL KNOWLEDGE AND
PROTECT HUMAN SUBJECTS?
AND I THINK THERE'S TWO MAIN
AVENUES OF LEARNING THAT WE HAVE
HAD.
ONE IS THROUGH HISTORICAL
LESSONS AND SUSAN LETTER IS
COMING AFTER ME AND TALKING
ABOUT SPECIFIC CASES IN THE
HISTORY OF HOW WE HAVE THOUGHT
ABOUT ETHICS AND CLINICAL
RESEARCH.
I'M GOING TO FOCUS MOSTLY ON THE
ETHICAL REASONS.
HOW DO WE THINK ABOUT IT
ETHICALLY.
I'LL START WITH ONE SLIDE ON
HISTORY BECAUSE SUSAN'S GOING TO
TALK ABOUT SPECIFIC CASES BUT I
THINK IF YOU LOOK OVER THE
TRAJECTORY OF TIME, THERE HAVE
BEEN ERAS OF DIFFERENCE IN TERMS
OF HOW WE THOUGHT ABOUT ETHICS
OF CLINICAL RESEARCH.
THERE WAS A LONG PERIOD OF TIME
WHERE THE ETHICS OF RESEARCH WAS
TOTALLY DEPENDENT ON THE
INDIVIDUALS DOING IT AND THEIR
PEER PRESSURE TO DO IT RIGHT.
THEN THERE WAS AN ADMITTEDLY NOW
UTILITARIAN PERIOD OF RESEARCH
WRITTEN ABOUT IN THAT WAY WHEN
THE IDEA WAS WE COULD ASK
PEOPLE, EVEN VULNERABLE AND
MARGINALIZED PEOPLE TO HELP
TREATMENT AND UNDERSTANDING OF
HEALTH FOR OTHERS, SOCIETY.
REALLY USING PEOPLE FOR THE
BENEFIT OF OTHERS IN A VERY
DIRECT WAY.
THAT LED TO A LOT OF SCRUTINY
ABOUT WHY ARE WE DOING THIS AND
WHAT IS THE SCOPE WE SHOULD BE
DOING?
SHOULD WE BE ALLOWING THAT KIND
OF RESEARCH?
SHOULD THERE BE RULES OR LIMITS
ON WHAT WE CAN DO TO PEOPLE TO
ANSWER QUESTIONS THAT MAY BE
USEFUL FOR OTHERS.
THAT LED TO AN ERA OF RULES AND
REGULATIONS.
THERE'S LOTS OF REGULATIONS PUT
INTO AFFECT.
MANY OF WHICH WE STILL OPERATE
UNDER.
AND THE ENTERPRISE OF CLINICAL
RESEARCH BECAME VERY WELL
REGULATED AND IS WELL REGULATED.
I'D SAY SUBSEQUENT TO THAT THERE
WAS A PENDULUM SWING TO
RECOGNIZING RESEARCH IS AN
IMPORTANT BENEFIT AND SOMETIMES
THE RULES AND REGULATIONS LIMIT
IT TOO MUCH AND DIMINISH THE
LIMITS OF DOING THE RESEARCH.
THIS IS BENEFITS RECOGNIZED ON
THE PART OF INDIVIDUALS WHO
WANTED TO BE PART OF RESEARCH
BECAUSE THEY FELT THEY COULD GET
BENEFIT FROM BEING A PART OF
RESEARCH AND ALSO FROM GROUPS
WHO SAID HOW ARE WE GOING TO
KNOW HOW TO TREAT CHILDREN
UNLESS WE INCLUDE CHILDREN IN
RESEARCH AND FOCUSSED ON
CHILDREN.
THAT'S THE KIND OF BENEFIT
THAT'S BEEN RECOGNIZED.
THROUGHOUT THESE DIFFERENT ERAS
OF HISTORY THERE'S BEEN A NUMBER
OF CODES AND REGULATIONS THAT
HAVE BEEN DEVELOPED.
I'M GOING TO SAY NOT MUCH ABOUT
ANY OF THESE BUT MAKE SURE THAT
YOU KNOW THEY'RE OUT THERE.
SOME OF THEM YOU'VE PROBABLY
HEARD ABOUT BEFORE LIKE THE
NUREMBERG CODE THE OUTCOME OF
THE NAZI DOCTOR'S TRIAL AND IT'S
A USEFUL DOCUMENT AND HAS A LOT
OF FORCE STILL BUT DOESN'T HAVE
ANY AUTHORITY REALLY YET HAS
GOOD TENETS TO IT.
THE FIRST ONE IS ABOUT VOLUNTARY
CONSENT AND THAT HAS BEEN THE
SOURCE OF A LOT OF FOCUS ON THE
NEED FOR CONSENT IN RESEARCH.
THE DECLARATION OF HELSINKI WAS
WRITTEN BY THE WORLD MEDICAL
ASSOCIATION WHICH IS AN
ASSOCIATION OF ALL OF THE
AMERICAN MEDICAL ASSOCIATIONS
AROUND THE WORLD FROM THE
DIFFERENT COUNTRIES.
THEY WROTE IT ACTUALLY IN THE
'60s INITIALLY BECAUSE OF THE
REACTION TO THE CODE WAS WELL,
THAT'S FOR PRISONERS.
WE WANTED A CODE FOR DOCTORS
TREATING AND ENROLLING PATIENTS
IN RESEARCH.
THEY WROTE THAT DECLARATION
INITIALLY IN 1964.
IT'S BEEN REVISED AT LEAST SIX
OR SEVEN TIMES, RECENTLY IN
2013.
MY UNDERSTANDING IS THAT IT'S
CURRENTLY BEING REVISED AGAIN.
DECLARATION OF HELSINKI DOES
HAVE A LOT OF FORCE AROUND THE
WORLD AND HAS BEEN THE SOURCE OF
A LOT OF CONTROVERSY.
SOME OF THE TENETS OF THE
DECLARATION HAVE BEEN DEBATED
QUITE HEAVILY OVER THE YEARS AND
I CAN TALK ABOUT THAT LATER IF
PEOPLE ARE INTERESTED.
THE BELMONT REPORT, HOLLY
MENTIONED THE BELMONT REPORT
CAME OUT OF THE FIRST COMMISSION
IN THE UNITED STATES CALLED THE
NATIONAL COMMISSION FOR THE
PROTECTION OF HUMAN SUBJECTS OF
BIO MEDICAL AND BEHAVIORAL
RESEARCH A SHORT.
USUALLY REFERRED TO AS THE
NATIONAL COMMISSION.
AND THEY WROTE THE BELMONT
REPORT SAYING SOMETHING ABOUT IN
A MINUTE BECAUSE IT'S UNIQUE OR
DISTINCT IN SOME RESPECTS FROM
THE OTHERS.
THE CIOMS/WHO INTERNATIONAL
GUIDELINES WERE WRITTEN
INITIALLY IN 1993 IT'S FOR
COUNCIL OF INTERNATIONAL
ORGANIZATION AND IT'S WHEN
THERE'S A COUNTRY DOING RESEARCH
COLLABORATIVELY OR NOT WITH A
HOST COUNTRY WITH LESS
RESOURCES.
SO THE CIOMS INITIALLY THE
INTERNATIONAL GUIDELINES TOOK
THE PRINCIPLES IN THE
DECLARATION OF HELSINKI AND
TRIED TO ELABORATE ON THEM FOR
THE CONTEXT OF INTERNATIONAL
COLLABORATIVE RESEARCH.
THEY'VE ALSO BEEN REVISED
SEVERAL TIMES.
RECENTLY IN 2016.
ONE OF THE NICE THINGS FROM MY
PERSPECTIVE THESE GUIDELINES NOT
ONLY ARE THERE TENETS BUT
THERE'S EXPLANATIONS OF WHY THEY
THINK IT'S AN IMPORTANT TENET.
THEIR REASONING BEHIND THEIR
PRINCIPLES ARE IN THE DOCUMENT.
THEN I KRIF H/GCP THE
INTERNATIONAL CONFERENCE ON
HARMONIZATION.
GOOD CLINICAL PRACTICE
GUIDELINES -- ICH/GCP.
THIS IS FROM RECOGNITION THAT
OFTEN TIMES RESEARCH IS BEING
DONE IN ONE PART OF THE WORLD
AND THE RESULT ARE TO BE ADOPTED
IN ANOTHER PART OF THE WORLD.
THERE'S REGULATORY AGENCIES IN
EVERY COUNTRY.
TO AVOID HAVING TO REPEAT
RESEARCH IN EVERY COUNTRY THAT'S
GOING TO TRY TO REGULATE IT A
NUMBER OF COUNTRIES GOT TOGETHER
I THINK INITIALLY IN THE 1990s
AND PUT TOGETHER THE ICH/GCP
SAYING IF COUNTRIES FOLLOWED
THOSE GUIDELINE THE REGULATORY
AUTHORITIES WOULD ACCEPT THE
DATA THAT CAME FROM THE RESEARCH
DONE IN THAT WAY.
AND ICH/GCP ADOPTS THE ETHICAL
GUIDANCE THAT CAME FROM THE
DECLARATION OF HELSINKI.
THOSE ARE DIFFERENT FROM THE
REGULATIONS.
AND THESE ARE SELECTIVE
REGULATIONS.
IN THE UNITED STATES, THE COMMON
RULE IS THE REGULATIONS THAT
GOVERN THE ETHICS OF RESEARCH
WITH HUMANS THAT'S FUNDED BY THE
FEDERAL GOVERNMENT.
SO ALL OF YOU WHO ARE LISTEN WHO
HAVE ANYTHING TO DO WITH NIH OR
RECEIVE NIH OR FEDERAL
GOVERNMENT GOVERNMENT FROM THE
UNITED STATES YOU HAVE TO FOLLOW
A COMMON RULE WHEN YOU DO
RESEARCH WITH HUMANS.
FDA HAS A SEPARATE SET OF
REGULATIONS AND THE REGULATIONS
ARE ACTUALLY QUITE SIMILAR TO
THE COMMON RULE BUT NOT
IDENTICAL.
AND FDA HAS A DIFFERENT MISSION
IN WHICH THE MISSION IS TO
PROTECT THE AMERICAN PUBLIC SO
THEY'RE CONCERNED WITH HOW DATA
ARE COLLECTED AND WHETHER
PRODUCTS THAT ARE TESTED SHOW
SAFETY AND EFFICACY.
MOST INSTITUTIONS INCLUDING THE
NIH HAS FURTHER POLICY AND GID
LINES WHICH GUIDE CLINICAL
RESEARCH.
THEN IF YOU'RE DOING
COLLABORATIVE RESEARCH AROUND
THE WORLD, MANY JURISDICTIONS
HAVE SIMILAR LAWS AND
REGULATIONS SPECIFIC TO THE
JURISDICTION.
SO THERE'S A LOT OF MOVING PARTS
HERE.
A LOT OF THINGS THAT NEED TO BE
PAID ATTENTION TO WHEN
SOMEBODY'S DOING RESEARCH.
I WANT TO SAY ONE ADDITIONAL
THING ABOUT THE BELMONT REPORT
AND I DIDN'T EVEN KNOW BUT IT'S
AN IMPORTANT DOCUMENT BECAUSE IT
BEGIN BY TRYING TO EXPLICATE THE
ETHICAL PRINCIPLES THAT UNDER
LIE -- UNDERLIE THE CONDUCT AND
RESPECT FOR PERSONS, BENEFICENCE
AND RESPECT FOR PERSONS APPLIED
TO PROCESS OF INFORMED CONSENT
AND BENEFICENCE APPLIED TO HOW
WE ASSESS RISKS AND BENEFITS AND
JUSTICE TO HOW WE SELECT
PARTICIPANTS IN STUDIES AND
ASSURE SOME DISTRIBUTION OF THE
BENEFITS AND BURDENS OF
RESEARCH.
IT'S A VERY USEFUL DOCUMENT.
IT'S A RELATIVELY SHORT
DOCUMENT.
EASY TO READ AND USEFUL FOR
THINKING ABOUT THE KINDS OF
CHALLENGES WE FACE IN RESEARCH
THOUGH IT'S 50 YEARS OLD.
AND ANOTHER THING THAT'S
INTERESTING AND IMPORTANT IS
SPELL OUT THE BOUNDARIES BETWEEN
CLINICAL PRACTICE AND CLINICAL
RESEARCH.
HOW THEY'RE DIFFERENT.
I'M SAIL A LITTLE BIT MORE ABOUT
THAT IN A MINUTE.
THE DIFFERENCE BETWEEN RESEARCH
AND CLINICAL PRACTICE I THINK IS
IMPORTANT FOR THINKING ABOUT THE
ETHICAL TENSIONS THAT WE
SOMETIMES FACE WHEN WE'RE DOING
RESEARCH.
HERE'S SOME OF THE DIFFERENCES.
THEY HAVE DIFFERENT GOALS.
I ALREADY MENTIONED THE FACT
THAT RESEARCH, THE GOAL OF
RESEARCH IS TO GENERATE USEFUL
KNOWLEDGE THAT WILL HELP US
BETTER UNDERSTAND HEALTH AND
DISEASE AND HOW TO BETTER
DIAGNOSE AND TREAT IT.
CLINICAL PRACTICE ON THE OTHER
HAND, THE GOAL IS TO BENEFIT THE
PERSON OR PEOPLE FOR WHOM YOU'RE
INTERACTING WITH.
YOU USE THE EVIDENCE THAT'S BEEN
GENERATED BY RESEARCH HOPEFULLY
IN THE PAST TO SAY WHAT'S THE
BEST THING I CAN DO TO PROMOTE
THE WELFARE OF THIS PERSON OR
THIS GROUP IN FRONT OF ME.
SO THE GOALS ARE VERY DIFFERENT
BETWEEN RESEARCH AND PRACTICE.
THERE'S ALSO DIFFERENT METHODS.
IN CLINICAL RESEARCH IT'S NOT
UNCOMMON FOR US TO RANDOMIZE
PEOPLE.
DRUG A OR DRUG B OR USE A
PLACEBO SAYING WE'LL GIVE YOU
DRUG A BUT YOU'RE GOING TO GET A
SUGAR PILL OR USE DOSE
ESCALATION.
THE LOWEST DOSE AND INCREASE
WITH COHORTS OF PEOPLE.
OR TO BLIND THE ASSIGNMENT OF
TREATMENT, IN OTHER WORDS, YOU
GET DRUG A AND DRUG B BUT YOU'RE
NOT GOING TO KNOW WHICH ONE
YOU'RE GETTING AND I'M NOT GOING
TO KNOW EITHER AS THE
INVESTIGATOR.
THOSE METHODS ARE IMPORTANT TO
INCREASE THE RIGOR AND
RELIABILITY OF RESEARCH AND
RESEARCH RESULTS.
BUT THEY'RE NOT METHODS YOU
WOULD SEE IN CLINICAL PRACTICE.
IF YOU WENT TO YOUR DOCTOR AND
THEY SAID TO YOU, I'M GOING TO
GIVE YOU A PILL FOR YOUR STREP
THROAT BUT I'M NOT GOING TO KNOW
WHAT IT IS AND NEITHER ARE YOU,
YOU'LL SAY LIKE, WHAT?
WHY AM I HERE?
I'M NOT COMING TO THIS DOCTOR
ANYMORE.
THERE'S ALSO DIFFERENT
JUSTIFICATION FOR RISK.
CERTAINLY IN PRACTICE SETTING
INTERVENTIONS WE USE FOR
DIAGNOSTIC PREVENTION AND
TREATMENT PURPOSES ALL HIGH
RISKS BUT THE RISKS ARE
JUSTIFIED BECAUSE THE
INTERVENTION IS THOUGHT TO BE
BENEFICIAL FOR THIS PERSON AT
THIS TIME.
THAT'S WHY WE DO IT.
IN RESEARCH WE SOMETIMES ASK
PEOPLE TO ACCEPT RISK FOR THINGS
NOT FOR THEM AT ALL.
WE'LL ASK FOR AN EXTRA BLOOD
DRAW OR A BIOPSY OR IMAGING OR
SOME KIND OF TEST SOLELY DONE
FOR THE PURPOSES OF RESEARCH AND
HAS NO IMPLICATIONS FOR THE
WELFARE OF THE INDIVIDUAL BEING
ASKED TO DO IT.
OF COURSE THERE'S DIFFERENT
LEVELS OF UNCERTAINTY.
IN CLINICAL PRACTICE, WE HOPE
PEOPLE USE EVIDENCE THAT EXISTS
AND EXPERIENCE TO SAY YOU HAVE
THIS DISEASE, THIS IS HOW IT
SHOULD BE TREATED BECAUSE I KNOW
THE EVIDENCE, I'VE DONE THIS
BEFORE.
THIS IS WHAT THE GUIDELINES SAY.
IN RESEARCH WE START WITH
UNCERTAINTY.
THE ONLY REASON TO DO RESEARCH
IS BECAUSE WE DON'T KNOW THE
ANSWER TO THOSE QUESTIONS.
IN ORDER TO TRY TO REDUCE
UNCERTAINTY OR UNDRESS
UNCERTAINTY WE DO RESEARCH.
RESEARCHERS HAVE DIFFERENT
OBLIGATIONS.
CLINICIANS HAVE AN OBLIGATION TO
OFFER CARE AND TREATMENT IN
THEIR PATIENT'S BEST INTEREST
AND RESEARCHERS HAVE AN
OBLIGATION TO CONFIDENTLY
CONDUCT RESEARCH WHILE
RESPECTING AND PROTECTING THE
RIGHTS AND WELFARE OF THEIR
SUBJECTS OR PARTICIPANTS.
SO HERE'S WHERE I LAND AT THIS
POINT.
I'VE GIVEN YOU SIX CODES OF
ETHICS, SIX REGULATIONS, LOTS OF
HISTORY, LOTS OF DETAILS AND I
THINK WHAT ENDS UP HAPPENING AT
SOME POINT FOR MANY PEOPLE WHO
ARE EITHER DOING RESEARCH,
CONDUCTING RESEARCH AS
RESEARCHERS, REVIEWING RESEARCH
AS IRB MEMBERS OR INTERESTED
OTHERS INTERESTED IN THE ETHICS
RESEARCH THEY'RE LIKE OKAY, HOW
DO I KNOW IT'S THE MOST
IMPORTANT THING?
HOW DO I PUT ALL THIS TOGETHER.
THE INTERESTING THING ABOUT THE
CODES AND REGULATIONS IS THEY'RE
NOT ALL THE SAME.
MANY OF THEM WERE DEVELOPED IN
RESPONSE TO SPECIFIC HISTORICAL
EVENT.
SO AS A MENTIONED, THE NUREMBERG
CODE CAME FROM WORLD WAR II IN
THE NAZI DOCTOR TRIAL AND THE
BELMONT REPORT CAME AFTER THE
EXPOSITION OF THE RESEARCH DONE
IN THE TUSKEGEE STUDY YOU'LL
HEAR ABOUT LATER.
THE GUIDANCE THAT DOES EXIST WAS
IN RESPONSE TO SPECIFIC
HISTORICAL EVENTS AND THEREFORE
EMPHASIZES OR RESPONDS TO THINGS
THAT HAPPENED HISTORICALLY.
THEREFORE THEY'RE NOT IDENTICAL.
THEY HAVE DIFFERENT REQUIREMENTS
AND DIFFERENT EMPHASISES.
-- EMPHASIS AND YOU CAN READ
ONE IN THE DECLARATION OF
HELSINKI THAT DOESN'T MATCH WHAT
YOU READ IN THE ICHP.
AND WE THOUGHT THERE WAS A NEED
FOR A SYSTEMATIC COHERENT
UNIVERSALLY APPLICABLE FRAMEWORK
FOR THINKING OF THE ETHICS OF
CLINICAL RESEARCH AND THAT'S THE
FRAMEWORK I'LL INTRODUCE YOU TO.
AS HOLLY SAID THIS WILL COME UP
OVER AND OVER AGAIN THROUGHOUT
THE COURSE BECAUSE PEOPLE USE IT
TO DIVE INTO SPECIFIC AREAS.
I'LL DO A VERY BROAD OVERVIEW.
THE FRAMEWORK HAS EIGHT
PRINCIPLES.
COLLABORATIVE PARTNERSHIP,
VALUABLE SCIENTIFIC QUESTION,
VALID METHODOLOGY, FAIR SUBJECT
SELECTION, FAVORABLE INDEPENDENT
REVIEW AND INFORMED CONSENT AND
WHAT IS COLLABORATIVE
PARTNERSHIP?
IF YOU THINK OF THE GOAL OF
CLINICAL RESEARCH AS DEVELOPING
USEFUL KNOWLEDGE, THE YOUTHFUL
KNOWLEDGE IS ONLY YOUTHFUL IF
IT'S PERCEIVED AS YOUTHFUL BY
LOTS OF OTHER PEOPLE NOT JUST
THE RESEARCHER THEMSELVES.
SO IN THAT REGARD, ETHICAL
RESEARCH SHOULD BE A
COLLABORATIVE PARTNERSHIP WITH
THE RELEVANT PARTNERS AND THAT
COULD BE COLLABORATION IN THE
PLANNING, IN THE CONDUCTING, IN
THE OVERSEEING OF RESEARCH AND
ALSO COLLABORATION IN
INTEGRATING ANY RESEARCH RESULTS
INTO A HEALTH SYSTEM OTHERWISE
THEY WOULD BE USEFUL.
IT ALSO CALLS FOR RESPECT FOR
THE CONTRIBUTIONS OF THE VARIOUS
PARTNERS.
AND COLLABORATION WITH THE
EXISTING SYSTEMS OF HEALTH
USEFUL INFORMATION CAN BE
INTEGRATED.
PARTNERSHIPS COULD BE WITH A
BUNCH OF PEOPLE AND IT DEPENDS
ON THE RESEARCH, THE PURPOSE OF
THE RESEARCH, THE SETTING FOR
THE RESEARCH AND MANY OTHER
FACTORS BUT YOU MIGHT IMAGINE
COLLABORATIVE PARTNERS WITH
PATIENT ADVOCATES AND ADVOCATES
FOR FUNDING, INVESTIGATORS,
ESPECIALLY COLLABORATING
INVESTIGATORS, CLINICIANS,
PARTICIPANTS AND THERE COULD BE
OTHERS AND YOU MAY HEAR OF SOME
OF THEM AND COMMUNITY ADVISORY
BOARDS, COALITION OF PATIENTS
THAT WORK TOGETHER AS ADVOCACY
GROUPS AND THERE ARE ADVISORY
GROUPS FOR THIS TOP RIGHT CORNER
IS A GROUP AT THE NIH THAT
ADVISES THE NIH ON PRIORITY
SETTING.
YOU COULD SEE AT THE BOTTOM, IN
MANY COUNTRIES AROUND THE WORLD
THERE ARE WAYS TO ENGAGE
COMMUNITIES IN DISCUSSIONS ABOUT
WHAT RESEARCH SHOULD BE DONE AND
HOW RESEARCH SHOULD BE DONE IN A
PARTICULAR CASE.
SO THERE ARE LOTS OF EXAMPLES OF
THIS.
THERE'S ALSO INTERESTING
CHALLENGES.
ONE IS HOW DO YOU IDENTIFY WHO
THE PARTNERS OUGHT TO BE IN THE
PARTICULAR CASE?
AND I THINK THAT'S A REALLY
INTERESTING CHALLENGE BECAUSE
YOU SAW THAT LIST I GAVE BUT
THAT LIST WAS NOT ALL INCLUSIVE.
THERE MIGHT BE OTHERS.
IN SOME CASES, THE PARTNERS
OUGHT TO BE ONE GROUP WITHOUT SO
MANY OF THE OTHERS BUT FIGURING
OUT WHO THE RIGHT PARTNERS ARE.
THEN THERE'S REALLY INTERESTING
DEEP QUESTIONS, UNRESOLVED
QUESTIONS ABOUT THE METHODS OF
ENGAGEMENT.
ONE COULD IMAGINE, FOR EXAMPLE,
YOU HAVE A VERY ACTIVE COMMUNITY
ADVISORY BOARD AND THAT'S A
PARTNERSHIP THAT COULD INFLUENCE
THE RESEARCH AND COULD BE REALLY
A VERY IMPORTANT PART OF HOW YOU
DECIDE TO DO RESEARCH.
BUT THE PARTICIPANTS IN THE
STUDY DON'T FEEL LIKE THEY'RE
ENGAGED AT ALL OR YOU ENGAGE
PEOPLE IN REVIEWING A CONSENT
FORM BUT DON'T IS THIS A STUDY
THAT SHOULD BE DONE HERE OR IS
THERE A DIFFERENT WAY WE SHOULD
BE DOING IT?
I PULLED RANDOMLY AN ARTICLE
FROM THE NEW ENGLAND JOURNAL
FROM THIS WEEK JUST TO GIVE YOU
A FLAVOR OF THE COMPLEXITY OF SO
MUCH RESEARCH AND THIS ISN'T
EVEN THE MOST COMPLEX BUT THAT
THE 292 INFANTS AT 39 CENTERS IN
EUROPE ACROSS MULTIPLE COUNTRIES
AND YOU CAN SEE THE NUMBER OF
COLLABORATING INVESTIGATORS WHO
ARE AUTHORS ON THE PAPER AND THE
LAST SENTENCE OF THAT AUTHORSHIP
IS FOR THE PREDICT STUDY GROUP.
SO THERE'S A LARGER GROUP
INVOLVED IN THIS.
THINKING ABOUT THE PARTNERSHIPS
HERE WITH THE COLLABORATORS IS A
COMPLICATED THING BUT IMPORTANT
FOR THE SUCCESS OF RESEARCH.
THE SECOND PRINCIPLE IN THE
FRAMEWORK IS THE VALUABLE
SCIENTIFIC QUESTION.
THIS BASICALLY MEANS IF RESEARCH
IS THE GOAL IS TO GENERATE
USEFUL KNOWLEDGE THEN THE
QUESTION IS BEING ASKED IN ANY
PARTICULAR CASE HAS TO BE ONE
THAT WILL GENERATE USEFUL
KNOWLEDGE.
THERE HAS TO BE A QUESTION WORTH
ASKING.
ONE THAT WILL GENERATE NEW
KNOWLEDGE OR UNDERSTANDING ABOUT
HUMAN HEALTH OR ILLNESS THAT'S
SOCIALLY, CLINICALLY OR
SCIENTIFICALLY USEFUL.
THIS IS A REALLY IMPORTANT
PRINCIPLE IN DISTINGUISHING THE
DIFFERENCE BETWEEN CLINICAL
RESEARCH AND PRACTICE.
IN CLINICAL PRACTICE WE DON'T
CARE ABOUT THIS.
CLINICAL RESEARCH IT'S NOT ONE
OF THE FIRST THINGS WE SHOULD
CARE ABOUT.
HOW WILL THE RESEARCH ADD VALUE?
THERE ARE LOTS OF INTERESTING
CHALLENGES ABOUT THIS AS WELL.
ONE IS HOW DO WE FIGURE OUT THE
VALUE OF ANSWERING THE RESEARCH
QUESTION AND HYPOTHESIZE WHAT
WE'LL LEARN AND HOW USEFUL
LEARNING IT WILL BE AND IN WHAT
WAY IT WILL BE USEFUL BUT
THERE'S QUESTIONS ABOUT HOW THAT
VALUE WILL BE JUDGED ESPECIALLY
AT THE FRONT END AND TO WHOM THE
KNOWLEDGE WILL BE VALUABLE.
IT COULD BE A NUMBER OF
DIFFERENT GROUPS BUT THERE ARE
SOME DEBATES ABOUT LOCAL SOCIAL
VALUE VERSUS LARGER SOCIAL VALUE
AND THINGS LIKE THAT.
THERE'S BEEN A LOT OF REALLY
INTERESTING BIOETHICS LITERATURE
ON THIS QUESTION ON SOCIAL VALUE
IN THE LESS THAN 10 YEARS.
THIS WAS A WHOLE ISSUE OF THE
JOURNAL BIOETHICS DEDICATED TO
SOCIAL VALUE WITH DEBATES ABOUT
IF IT'S REALLY IMPORTANT HOW DO
WE UNDERSTAND WHAT IT IS.
PEOPLE ARGUING WHETHER DIFFERENT
KINDS OF RESEARCH NEED TO HAVE
SOCIAL VALUE AND OTHERS DON'T.
LOTS OF DEBATES ABOUT THAT.
AND I GOT TO PUT A CHAPTER
TOGETHER WITH ONE OF MY FELLOWS
A COUPLE YEARS AGO WHERE WE
TRIED TO LOOK BACK AND SAY,
LET'S LOOK THROUGH THE
LITERATURE AND THINK OF CASES
THAT REALLY WERE EXEMPLARS OF
HIGH SOCIAL VALUE AND LOW SOCIAL
VALUE AND TRY TO SORT THIS OUT.
IT WAS AN INTERESTING EXERCISE.
I THINK YOU MIGHT ENJOY READING
IT IF YOU'RE INTERESTED IN THE
TOPIC.
I WILL SAY WE GOT PUSHBACK FOR
THE FOLLOWING REASON BECAUSE
THEY WERE CASES OF RESEARCH
ALREADY DONE AND SO JUDGING
SOCIAL VALUE POST RESEARCH IS
DIFFERENT THAN JUDGING IT AT THE
FRONT END.
THE THIRD PRINCIPLE IN THE
FRAMEWORK IS VALID SCIENTIFIC
METHODOLOGY.
THIS BASICALLY SAYS YOU'VE GOT
YOUR PARTNERS, YOU GOT A
QUESTION WORTH ADDRESSING, NOW
YOU'VE GOT A STRUCTURE THE STUDY
SO YOU GET AN ANSWER YOU CAN
INTERPRET AND USE.
AND SO IT SHOULD BE DESIGNED IN
A METHODOLOGICALLY MANNER TO BE
FEASIBLE.
THIS COVERS A LOT OF TERRITORY.
ONE OF THE THINGS SOME PEOPLE
HAVE SAID OVER MANY YEARS ABOUT
THIS PRINCIPLE IN THE ETHICAL
FRAMEWORK IS WHY DO WE CARE
ABOUT SCIENCE.
IT'S NOT ETHICS, IT'S SCIENCE.
BUT SCIENCE AND ETHICS ARE
INEXTRICABLY COMBINED.
SO ALL THESE, EVERY SCIENTIFIC
DECISION YOU MAKE IN DESIGNING A
TRIAL OR DECIDING HOW TO CONDUCT
A TRIAL HAS ETHICAL IMPLICATIONS
AND ETHICAL SCIENCE.
WHAT ARE SOME THINGS PEOPLE MAY
BE DEBATING IN TERMS OF
SCIENTIFIC VALIDITY?
WHAT END POINTS DO YOU WANT IN A
GIVEN STUDY.
WHAT KIND OF DESIGN FOR A DOUBLE
BLIND CONTROL OR A
NON-INFERIORITY OR SUPERIORITY
DESIGN OR TO BE QUALITATIVE OR
QUANTITATIVE DESIGN?
CHOICES OF PROCEDURE, CHOICES OF
STATISTICAL METHODS OR
ANALYTICAL METHODS AND
IMPORTANTLY FEASIBILITY.
IF A STUDY DESIGN IN A WAY THAT
IS IMPOSSIBLE TO DO, IN OTHER
WORDS, YOU CAN'T MEASURE WHAT
YOU'RE HOPING TO MEASURE OR YOU
COULDN'T BE ABLE TO GET PEOPLE
TO -- THERE AREN'T PEOPLE TO
ENROLL OR YOU WOULDN'T BE ABLE
IT GET THEM TO ENROLL, IT'S NOT
AN ETHICAL STUDY BECAUSE YOU
CAN'T FINISH IT.
YOU SHOULDN'T START IT IF YOU
KNOW YOU CAN'T FINISH IT.
THERE'S LOTS OF WAYS TO THINK
ABOUT THIS CONCERN ABOUT AND
WAYS PEOPLE THINK ABOUT THE
ETHICS OF SCIENTIFIC VALIDITY
AND STUDY DESIGN.
MOST I'LL REPRESENT IN CARTOONS.
YOU HAVE A CONTROL AND OUT OF
CONTROL GROUP.
WE HAVE CARTOONS THAT SAY I DIED
AS A MEMBER OF THE PLACEBO GROUP
AND WE HAVE INTERESTING
STATISTICS AND HOW THEY CAN BE
USED TO MAKE YOUR OWN
CONCLUSIONS OR TO MAKE WRONG
CONCLUSION.
THERE'S LOTS OF INTERESTING
EXAMPLES OF SCIENTIFIC VALIDITY
QUESTIONS TO BE ADDRESSED.
THERE'S NEWER STUDY DESIGNS
WHICH STILL NEEDS ATTENTION FROM
THE PERSPECTIVE OF ETHICS.
DECENTRALIZED TRIALS EXPLODED
DURING THE PANDEMIC.
THE BASIC IDEA IS PEOPLE
PARTICIPATE FROM HOME OR FROM
THEIR OWN CLINICAL PRACTICE AND
ALL THE INTERACTIONS ARE REMOTE.
IN OTHER WORDS, CONSENT IS
ELECTRONIC AND INTERACTION
EITHER THROUGH TELEMEDICINE OR
FOR SOMEBODY ELSE VISITING THE
HOME.
DATA IS COLLECTED AND SENT
DIGITALLY.
IT'S AN INTERESTING MODEL THAT'S
BEING USED.
A LOT OF PEOPLE WORRY ABOUT
THINGS LIKE RELIABILITY OF DATA.
ISOLATION OF PARTICIPANTS.
THERE'S INTERESTING ISSUES
RAISED BUT IT NEEDS MORE
ATTENTION FROM AN ETHICAL
PERSPECTIVE.
PRAGMATIC TRIALS HAVE GOTTEN A
FAIR AMOUNT OF ATTENTION IN THE
LAST EIGHT OR 10 YEARS.
IT'S THE KIND OF TRIAL THAT'S
DONE NOT COMPLETELY UNCERTAIN
ABOUT A NEW INTERVENTION BUT
MORE LIKE TWO DRUGS FOR
HYPERTENSION AND THEY BOTH SEEM
TO WORK.
SOME PEOPLE THINK ONE'S BETTER
THAN THE OTHER AND ONE HAS MORE
SIDE EFFECTS SO THEY SET UP
HEAD-TO-HEAD TRIALS.
THERE'S RIGOROUS DEBATES HOW
CONSENT OUGHT TO BE OBTAINED AND
OTHER THINGS ABOUT PRAGMATIC
TRIALS.
PEOPLE IN OUR DEPARTMENT ARE
WORKING ON THAT.
PLATFORM TRIALS, AGAIN,
SOMETHING RELATIVELY NEW
EXPLODED DURING COVID.
THE IDEA BEING THAT YOU HAVE A
TRIAL WHERE YOU CAN HAVE ONE
CONTROL GROUP AND ROTATE IN AND
OUT OF THE EXPERIMENTAL
INTERVENTION SO YOU DON'T HAVE
TO COMPLETELY GET A NEW CONTROL
OVER TIME.
IN THEORY IT'S A GREAT MODEL.
IN PRACTICE IT'S A LITTLE MORE
COMPLICATED THAN IT SOUNDS.
THERE'S INTERESTING THINGS TO
THINK ABOUT.
THEN FOR NOW AT LEAST 10 YEARS
WE'VE BEEN ARGUING ABOUT HOW DO
WE THINK WITH THE ETHICS OF
RESEARCH DONE WITH STORE SAMPLES
AND BIO SPECIMENS.
HOW THEY'RE OBTAINED TO BEGIN
WITH, HOW THEY'RE STORED, WHO
GETS TO USE THEM AND WHAT
PERMISSION YOU NEED TO USE THEM.
ETCETERA.
THE NEXT PRINCIPLE IS FAIR
SUBJECT SELECTION.
COLLABORATIVE PARTNERSHIP,
SOCIAL VALUE, SCIENTIFIC
METHODOLOGY AND THIS IS THE
FOURTH.
ONCE YOU'VE GOT A DESIGN AND
PROCESS BY WHICH YOU THINK YOU
WANT TO RUN THE STUDY, THERE
NEEDS TO BE SOME DECISIONS ABOUT
WHO GETS ENROLLED AND WHO GETS
INVITED TO PARTICIPATE.
AND OF COURSE THE SCIENTIFIC
OBJECTIONS SHOULD GUIDE
INCLUSION CRITERIA.
AND RECRUITMENT STRATEGIES AND
SELECTION AND THE BELMONT FOR
EXAMPLE TALKS ABOUT PARTICIPANTS
SHOULD BE SELECTED BASED ON
SCIENCE NOT PRIVILEGE OR EASY
AVAILABILITY OR VULNERABILITY.
AND THOSE ARE THINGS THAT
HISTORICALLY HAVE HAPPENED.
ONE OF THE WAYS TO THINK ABOUT
FAIR SUBJECT SELECTION IS
FLIPPING IT ON ITS HEAD, SO TO
SPEAK AND SAY EVERYBODY SHOULD
BE ELIGIBLE.
EVERYBODY SHOULD BE INCLUDED
UNLESS THERE'S REASONS TO
EXCLUDE THEM.
THE TWO REASONS PEOPLE PULLED
OUT TO SAY -- WELL, THREE, TWO
AND A HALF I'LL SAY WHY.
REASONS TO EXCLUDE SOMEBODY
SCIENTIFICALLY TOTALLY
INAPPROPRIATE.
IF YOU'RE STUDYING A TREATMENT
FOR BREAST CANCER YOU NEED
PEOPLE WHO HAVE BREAST CANCER TO
BE IN THE STUDY.
THERE MAY BE RISK-RELATED
REASONS FOR EXCLUSION.
MAYBE IN THE SAME STUDY THE
INTERVENTION IS ALREADY KNOWN TO
HAVE SERIOUS RENAL TOXICITY.
YOU MAY EXCLUDE PEOPLE WHO HAVE
POORER KIDNEY FUNCTION.
THE THIRD OR THE HALF
JUSTIFICATION THAT SOMETIMES
PEOPLE USE IS VULNERABLE.
AND VULNERABLE IS A COMPLICATED
TOPIC AND YOU CAN HAVE A WHOLE
SESSION ON IT IN A COUPLE WEEKS
SO I WON'T SPEND TOO MUCH TIME
BUT THERE ARE PEOPLE WHO SAY IF
VULNERABLE YOU SHOULD BE
EXCLUDED FROM CERTAIN KINDS OF
AND OTHERS SAY YOU SHOULD FIND
PEOPLE WHO ARE VULNERABLE.
IT DEPENDS ON WHY YOU'RE
VULNERABLE.
THERE'S A RECOGNIZED NEED TO
MAKE SURE THAT NOT JUST HOW
INDIVIDUALS ARE ASKED OR INVITED
OR SELECTED TO BE INVITED TO
PARTICIPATE IN A STUDY BUT ALSO
HOW WE THINK WITH THE GROUPS.
HOW DO WE FAIRLY DISTRIBUTE THE
POSSIBLE HARMS OF DOING RESEARCH
AND THE POSSIBLE BENEFITS.
SO YOU WOULDN'T WANT TO GO TO
THE SAME ENCLAVE OF PEOPLE WHO
ARE ALREADY BURDENED BY DISEASE
OR POVERTY AND ASK THEM TO
CONTINUALLY BE PARTICIPANTS IN
RESEARCH ESPECIALLY IF THEY'RE
NOT GETTING ALL THE BENEFITS OR
BENEFITS NEVER GO TO THEM.
THINKING ABOUT THE DISTRIBUTION
AN IMPORTANT PART OF FAIR
SUBJECT SELECTION.
THIS IS AN INTERESTING CHALLENGE
WHEN WE ARE THINKING ABOUT FAIR
SUBJECT SELECTION AND THAT IS
THAT FOR A LONG TIME AND SOME OF
THE GUIDANCE THAT EXISTS
SUGGESTS PARTICIPATING RESEARCH
IS A BURDEN AND PEOPLE NEED
PROTECTION.
BUT THERE'S ALSO THIS
RECOGNITION AND SOME GUIDANCE
RECOGNIZES IT CLEARLY THAT
RESEARCH IS A BENEFIT AND
PARTICIPANTS NEED ACCESS.
THERE'S A LITTLE BIT OF A
TENSION BETWEEN THE TWO AND
THERE'S BEEN A SWING BACK AND
FORTH BETWEEN THE TWO AND ONE
THAT COMES UP QUITE A BIT.
THERE ARE ALSO SOME REALLY
INTERESTING CHALLENGES.
I MENTIONED PROTECTING THE
VULNERABLE GROUPS YOU'LL HEAR
MORE ABOUT.
I WANT TO PUT TWO QUESTIONS TO
THINK ABOUT.
ONE IS THINKING ABOUT WHO THE
APPROPRIATE PARTICIPANTS ARE AND
IT HAPPENS ALL THE TIME.
FOR EXAMPLE IN THE STUDY TESTING
AN EARLY POTENTIALLY RISKY
THERAPY IN A GENETIC DISORDER,
IS IT BETTER TO ENROLL OR TO
INVITE FIRST HEALTHY AFFECTED
ADULTS WHO CAN CONSENT BUT HAVE
MILD DISEASE?
THAT'S WHY THEY LIVE TO THE AGE
THEY ARE OR TO TEST IT IN
SEVERELY ILL INFANTS WHO ARE
OTHERWISE NOT GOING TO MAKE IT
PAST INFANCY?
THAT'S A REAL LIVE QUESTION
THAT'S BEEN DEBATE AND DECIDED
IN DIFFERENT WAYS IN DIFFERENT
CASES.
ANOTHER ONE I'M PARTICULARLY
INTERESTED IN AND HAVE BEEN WORK
ON A LITTLE BIT OVER THE YEARS
IS ABOUT ENROLLING PREGNANT
PERSONS IN RESEARCH.
AGAIN, IT'S THIS SORT OF WE
RECOGNIZE THERE'S NOT A LOT OF
DATA FOR HOW TO TREAT SOMEONE
WHO IS PREGNANT ON THE OTHER
HAND ENROLLING SOMEONE WHO IS
PREGNANT INTO RESEARCH HAS LOTS
OF ETHICAL COMPLEXITIES AND
THINKING ABOUT THE CRITERIA IS A
CHALLENGING THING.
THE NEXT IS FAVORABLE RISK
BENEFIT.
THOUGH WE'VE DECIDED THIS STUDY
HAS VALUE AND IT'S SET UP IN A
WAY THAT CAN GET INTERPRETABLE
DATA THAT IS USEFUL AND WE MADE
CONSCIOUS DELIBERATE DECISIONS
WHO TO INVITE TO PARTICIPATE NOW
YOU THINK OF THE RISK AND
BENEFITS TO THE INDIVIDUALS IN
THE STUDY.
IS THERE A WAY TO MINIMIZE EVEN
MORE OR MINIMIZE OVER ALL THE
RISKS THAT AN INDIVIDUAL
PARTICIPANT IS EXPOSED TO?
ARE THEY JUSTIFIED BY POTENTIAL
BENEFIT TO THEM OR THE
IMPORTANCE OF THE SOCIAL VALUE
TO SOCIETY?
AND THEN A SEPARATE
CONSIDERATION THAT PEOPLE TALK
ABOUT ARE THE BENEFIT OR CAN THE
BENEFITS BE FURTHER ENHANCED?
YOU'LL HAVE A WHOLE SESSION ON
RISK AND BENEFIT.
THE BELMONT REPORT SAYS AND MOST
SAY IT'S CORRECT AND INTEREST ON
THOSE OTHER THAN THE SUBJECT MAY
BE SUFFICIENT BY THEMSELVES.
THIS MEANS YOU CAN ENROLL
SOMEBODY IN RESEARCH WHEN
THERE'S NO BENEFITS AT ALL TO
THAT INDIVIDUAL AS LONG AS THE
SUBJECT'S RIGHTS HAVE BEEN
PROTECTED AND I WOULD ADD AS
LONG AS THE STUDY HAS SOCIAL
VALUE.
THERE ARE SOME REALLY
INTERESTING CHALLENGES HERE AS
WELL.
IDENTIFYING WHICH RISKS AND
BENEFITS COUNT AND I THINK DAVE
WENDLER IS GIVING THAT LECTURE
AND DOES A GREAT JOB OF
CHALLENGING SHOULD THIS BE A
RISK.
THERE'S A CHALLENGE IN TERMS OF
HOW TO MINIMIZE THE RISKS.
PEOPLE SAY CAN YOU GET ENOUGH
DATA FROM THE MRIs TO GIVE YOU
THE INFORMATION YOU NEED?
THERE ARE REGULATIONS THAT LIMIT
RISKS FOR CERTAIN POPULATIONS SO
REGULATIONS THAT GUIDE RESEARCH
WITH CHILDREN LIMIT RISK TO
CHILDREN IN RESEARCH AN THERE'S
CATEGORIES OF LIMITS.
THERE'S LIMITS ON RISK WITH
PREGNANT PERSONS.
THERE'S LIMITS ON RISK WITH
PRISONERS.
THOSE ARE THE ADDITIONAL
REGULATIONS IN ADDITION TO THE
COMMON RULE.
THERE'S A LOT OF INTERESTING
DEBATES ABOUT DIRECT VERSUS
INDIRECT BENEFITS.
SOME PEOPLE SAY THE ONLY KIND OF
BENEFIT THAT SHOULD BE THOUGHT
OF WITH RESPECT TO AN INDIVIDUAL
PARTICIPANT ARE THE DIRECT BEN
FITS OF THE POTENTIAL DIRECT
BENEFITS FROM THE INTERVENTION
ITSELF AND NOT THE BENEFITS
PEOPLE SOMETIMES DESIRE LIKE
PAYMENT OR ACCESS TO GOOD
CLINICIAN OR ACCESS TO
TREATMENTS THEY OTHERWISE
COULDN'T GET AND THINGS LIKE
THAT AND THERE'S CHALLENGES IN
TERMS OF HOW DO WE DETERMINE AND
PEOPLE DISAGREE ABOUT THE LEVEL
OF RISK.
IS THIS MINIMAL RISK OR GREATER
THAN MINIMAL RISK AND PEOPLE
DISAGREE ABOUT PROSPECT AND
BENEFIT, WHAT IT IS AND HOW YOU
KNOW IT AND YOU'LL HEAR MORE
ABOUT THESE THINGS IN THIS
COURSE THE TWO MORE OR THREE
MORE INDEPENDENT REVIEW EXISTS
TO ENSURE THE REGULATORY AND
ETHICAL REQUIREMENTS HAVE BEEN
FULFILLED AND TO CHECK CONFLICTS
AND ASSURE THE PUBLIC THE
RESEARCH IS NOT EXPLOITIVE AND
THIS IS DONE IN THE UNITED
STATES BY INDEPENDENT
INSTITUTIONAL REVIEW BOARDS
AROUND.
AROUND THE WORLD THEY'RE OFTEN
CALLED RESEARCH ETHICS
COMMITTEES BUT THEY'RE REVIEW
BODIES OF PEERS USUALLY AND
NON-AFFILIATED PEOPLE WHO MAKE
SURE THESE THINGS ARE TRUE AND
THE CRITERIA IN THE COMMON RULE
AND IN THE FDA REGS FOR WHAT
IRBs SHOULD LOOK AT IN DECIDING
WHETHER TO APPROVE THE STUDY ARE
REFLECTIVE OF THE THINGS I
TALKED ABOUT.
ME RISKS ARE MINIMIZED,
JUSTIFIED BY ANTICIPATED
BENEFITS OR SOCIAL VALUE AND
FAIR SUBJECT SELECTION AND THE
NEXT THING I'LL TALK ABOUT IS
INFORMED CONSENT.
THERE'S A LOT OF INTERESTING
CHALLENGES WITH IRB'S.
INFORMED CONSENT.
THIS IS NOW THE SEVENTH OR THE
EIGHTH AND INTERESTINGLY WHEN WE
FIRST STARTED WORKING ON THIS
FRAMEWORK WE HAD TALKED TO LOTS
OF PEOPLE WHAT MAKES RESEARCH
ETHICAL?
THEY'D SAY, OH, INFORMED CONSENT
AND THERE WAS A PROLIFIC AND
WONDERFUL WRITER 30 YEARS AGO,
BENJAMIN FREEDMAN WHO WROTE AN
ARTICLE THAT SAID HE RAN INTO A
COLLEAGUE THAT WAS EXCITED AND I
JUST TRANSPLANTED MY FIRST
APPENDIX AND HE SAID HE GOT THE
INFORMED CONSENT.
AND USED THAT TO DESCRIBE
INFORMED CONSENT IS NOT THE WAY
TO MAKE RESEARCH ETHICAL.
THERE'S A BUNCH OF STUFF THAT
NEEDS TO HAPPEN FIRST AND HE
PROPOSES THE IDEA OF SOCIAL
VALUE.
THIS IS BASED ON RESPECT FOR
PERSONS.
THE RESPECT FOR THE CAPACITY AND
WRITE PEOPLE HAVE TO DECIDE
WHETHER THEY WANT TO PARTICIPATE
IN RESEARCH OR CONTINUE TO
PARTICIPATE AND WHETHER IT'S
COMPATIBLE WITH THEIR GOALS AND
INTERESTS.
WE'LL TALK ABOUT THIS NEXT WEEK.
THERE'S DIFFERENT PARTS TO
INFORMED CONSENT.
I WON'T GO INTO THEM NOW.
THERE ARE ALSO A LOT OF
CHALLENGES.
THE QUALITY OF INFORMED CONSENT
HAS BEEN SHOWN OVER AND OVER
AGAIN TO BE MODEST BUT AS WE
HOPED IT SHOULD BE, THERE'S LOTS
OF WAYS FOR THE CONSENT GOES.
THE CAPACITY TO CONSENT SAY
CHALLENGE AND I THINK SCOTT WILL
TALK ABOUT THAT NEXT WEEK.
THERE'S MANY APPROACH TO
INFORMED CONSENT.
I MENTIONED ELECTRONIC CONSENT.
THAT'S HAPPENED IN THE LAST 10
YEARS OR LESS.
LOTS OF NEW WAYS TO GET CONSENT.
AND HUGE DEBATES ABOUT THE
APPROPRIATE CONSENT METHOD FOR
USING BIO SAYS MENS COLLECTED A
LONG TIME AGO.
LAST BUT NOT LEAST IN THE
FRAMEWORK IS RESPECT FOR
ENROLLED PARTICIPANTS.
THIS ONE I THINK DOES NEED MORE
ATTENTION AND I WOULD SAY WHEN
WE WERE FIRST DEVELOPING THE
FRAMEWORK, WHEN WE REALLY DELVED
INTO THE OTHER GUIDANCE THAT
EXISTED, THE CODES AND
REGULATIONS AND LITERATURE,
THERE WAS THIS SORT OF IDEA IF
YOU WERE DOING ETHICAL RESEARCH
YOU HAD TO COME UP WITH A GOOD
IDEA AND HAD TO HAVE IT REVIEWED
FROM THE IRB AND HAVE TO HAVE IT
APPROVED AND ETHICS WERE DONE
AND THAT DIDN'T MAKE SENSE TO ME
AT ALL.
IN SOME RESPECTS YOU'RE JUST
BEGINNING.
YOU'RE BEGINNING OF A
RELATIONSHIP AND THE PARTNERSHIP
WITH THE PEOPLE IN THE STUDY AND
ALSO THE PEOPLE WHO YOU OWE THE
RESULTS TO.
ETHICAL RESEARCH REQUIRES
CONTINUED RESPECT FOR THE RIGHTS
AND WELFARE OF PARTICIPANTS OF
THE RESEARCH AND INCLUDES
PROTECTING CONFIDENTIALITY,
MONITORING THEIR WELFARE,
RECOGNIZING THEY HAVE A RIGHT TO
WITHDRAW WITHOUT REASON IF THEY
WANT.
PROVIDING NEW INFORMATION WHICH
IS A CHALLENGING THING AND
INCLUDING INFORMING THEM OF
FINDING AND PLANNING FOR WHAT
HAPPENS AFTER THE TRIAL ENDS.
AND SURPRISINGLY WE'RE BAD ADDS
A COMMUNITY IN GIVING
INFORMATION BACK TO PARTICIPANTS
AFTER THE STUDIES ARE OVER.
THEY DON'T ALWAYS KNOW WHAT
HAPPENED.
SOME PEOPLE DON'T KNOW AND YOU
CAN ASK THEM LATER WHETHER THEY
GOT PLACEBO OR NOT AND DON'T
KNOW THE RESULTS OF THE TRIAL
EITHER.
THERE'S A HUGE EFFORT TO TRY TO
THINK ABOUT WHAT ARE THE
OBLIGATIONS AND WHAT ARE
MECHANISMS FOR POST TRIAL ACCESS
TO INTERVENTIONS THAT PEOPLE ARE
BENEFIT FROM.
LAST SLIDE, THE FRAMEWORK IS
SYSTEMIC AND SEQUENTIAL.
YOU START AT THE PARTNERSHIP AND
GO TO WHAT HAPPENS AFTER THE
STUDY.
EACH ONE IS NECESSARY THOUGH THE
PROCEDURAL REQUIREMENTS CAN BE
WAVED UNDER CERTAIN
CIRCUMSTANCES AND THEY'RE
UNIVERSAL.
IN OTHER WORDS, ALL THOSE APPLY
IN EVERY SETTING AT EVERY TIME
AND YET THEY NEED TO BE ADAPTED.
SO HOW YOU THINK ABOUT RISKS AND
BENEFITS IN ONE CONTEXT MAY BE
VERY DIFFERENT THAN HOW YOU
THINK ABOUT IT IN ANOTHER
CONTEXT.
THAT'S APPROPRIATE BUT YOU STILL
HAVE TO THINK ABOUT RISKS AND
BENEFITS AND HOW TO MINIMIZE
THEM AND ENHANCE THE BENEFITS.
THEY REQUIRE BALANCING
SPECIFICATION AND JUDGMENT.
THAT'S WHY COURSES LIKE THIS
HOPEFULLY HELP PEOPLE TO BEGIN
TO GRAPPLE WITH HOW TO MAKE
THOSE KINDS OF JUDGMENTS AND HOW
TO THINK ABOUT HOW THE DIFFERENT
CONSIDERATIONS ARE AND HOW TO
MAKE DECISIONS ABOUT THAT.
THAT'S THE END.
>> THANK YOU SO MUCH, CHRISTINE.
SO WE NOW HAVE TEN MINUTES FOR
QUESTION
QUESTIONS.
THOSE IN THE ROOM YOU'LL SEE TWO
MICROPHONES.
QUICK, LINE UP WITH YOUR
QUESTIONS.
IF THOSE OUT IN VIDEO LAND WOULD
LIKE TO ASK A QUESTION, YOU CAN
POST IT ON THE DISCUSSION BOARD
IN CANVAS.
IT SAYS POSE QUESTIONS HERE.
YOU CAN ALSO SEND AN E-MAIL TO
BIOETHICS -- INQUIRIES AT MAIL
AT NIH.gov.
I DON'T YET HAVE QUESTIONS FROM
VIDEO LAND.
TAKE IT AWAY.
>>
>> YOU WILL HEAR A LOT ABOUT
EACH OF THE KEY PRINCIPLES THAT
WERE PRESENTED AS PRISTINE
MENTIONED NEXT WEEK WE'RE DOING
INFORMED CONSENT.
THIS IS THE SORT OF WELCOME TO
THE CLASS.
THESE ARE THE TOPICS WE'RE GOING
TO COVER.
>> WE COULD CHAT FOR SEVEN
MINUTES.
>> I THINK THE FRAMEWORK COULD
BE CHALLENGED ON A NUMBER OF
FRONTS.
WE STARTED WITH THE DISCLAIMER.
THIS IS OUR REASON AND NOBODY
ELSE'S AND WE PUBLISHED MULTIPLE
TIMES AND MULTIPLE WAYS AND
PEOPLE USED IT IN MULTIPLE WAYS.
THE FACT THAT SOME NATIONAL
REGULATIONS ADOPTED THE
FRAMEWORK AS THE WAY TO THINK
ABOUT HOW TO REVIEW A STUDY AND
THINK ABOUT WHAT WHETHER A STUDY
IS ETHICAL.
MAKES ME THINK IT'S USEFUL AND
IT WAS USEFUL PRODUCT TO PUT OUT
IN THE WORLD.
AS I MENTIONED THERE ARE
CHALLENGES TO EACH OF THOSE.
THERE ARE CHALLENGES TO HOW TO
DECIDE AND THERE'S ROOM FOR MORE
RESEARCH ON EACH OR EVERY ONE OF
THOSE.
>> PLEASE USE THE MIC WE HAVE
PEOPLE WHO HAVE IT HARD TO HEAR.
FEEL FREE TO SEND IN QUESTIONS.
WE USUALLY HAVE A CHATTY GROUP.
MAYBE PEOPLE ARE SLEEPING IN
TODAY.
>> THE FIRST QUESTION IS KIND OF
SIMPLE.
THE RATING HAD SEVEN ETHICAL
PRINCIPLES AND YOU ADDED THE
FIRST ONE AND I'M WONDERING
WHETHER THE FIRST ONE WAS
DEBATED OR HOW THAT PROCESS
WENT.
>> GREAT QUESTION.
WHEN WE FIRST STARTED REVIEWING
THE DOCUMENTATION THAT EXISTS IN
CODE AND LITERATURE AND WHAT WE
NEEDED.
WE HAD SEVEN AND STARTED WITH
SOCIAL VALUE AS THE FIRST AND
MOST IMPORTANT AND THEN WE TOOK
IT ON THE ROAD.
WE TOOK THE FRAMEWORK AND WENT
TO DIFFERENT GROUPS BOTH IN THE
UNITED STATES AND ALL AROUND THE
WORLD.
AND INTERNATIONAL COLLEAGUES
THOUGHT WE NEEDED SOMETHING
ABOUT COLLABORATION AND THAT'S
THE FIRST STARTING POINT BEFORE
YOU EVEN GET TO THE RESEARCH
QUESTION.
>> YOU HAD A SLIDE ABOUT THE
STANDARDS FOR MEDICAL CARE AND
MEDICAL RESEARCH.
I'M WONDERING ABOUT THE TENSION
WHEN CLINICAL RESEARCH IS THE
LAST RESORT FOR A PATIENT AND
WHETHER WE PRIORITIZE STANDINGS
OF MEDICAL CARE IN THOSE
SITUATIONS OR WHETHER OR NOT ONE
GOES TO THE OTHER.
>> I'LL EXPAND IT A LITTLE BIT.
THERE ARE CLEARLY TENSIONS
BETWEEN RESEARCH AND MEDICAL
CARE IN RESEARCH SETTINGS FOR
SEVERAL REASONS.
ONE IS BECAUSE MANY PEOPLE WHO
ARE CONDUCTING RESEARCH ARE
TRAINED AS CLINICIANS.
THEY FEEL THE PULL TO DO WHAT'S
BEST FOR THEIR PATIENT WHILE
THEY'RE ALSO IN THE BUSINESS OF
DOING WHAT'S RIGHT BY THE STUDY.
SOMETIMES STUDIES ARE STRICT IN
TERMS OF WHAT YOU CAN AN CANNOT
DO.
IN OTHER WORDS, WITH RESPECT TO
THINGS LIKE CHANGING DOSE OR
CHANGING DRUGS OR ADDING OR
SUBTRACTING THINGS.
YOUR QUESTION THOUGH IS
IMPORTANT IN TERMS OF WHEN YOU
THINK OF PEOPLE WITH SERIOUS
ILLNESSES WHO OFTEN TIMES HAVE
EXHAUSTED AVAILABLE STANDARD
CLINICAL OPTIONS FOR THEMSELVES,
HOW DO WE CONVENIENCE THAT
TENSION BETWEEN WHAT THE STUDY
IS ASKING AND WHAT THE PERSON
NEEDS.
THERE'S EXAMPLES OF GOOD AND BAD
OUTCOMES BUT CLINICAL
INVESTIGATORS HAVE ATTENTIVE TO
THE NEEDS OF THEIR PARTICIPANTS,
THEIR PATIENTS.
SO IF SOMEBODY IS NOT DOING WELL
ON A STUDY DRUG OR HAS
ADDITIONAL PROBLEM THAT NEEDS TO
BE ADDRESSED, THE STUDY WOULD
PRECLUDE THE STUDY FOR THEIR
MODIFICATION TO THE STUDY.
>> WE HAVE ONE MORE QUESTION
FROM KELLY.
>> CAN YOU CLARIFY MORE OF THE
DIFFERENCE BETWEEN DIRECT AND
INDIRECT WHEN YOU DO RISK
BENEFIT RATIO.
IT'S A HUGE DEBATE AND UNDER
ANALYZED DEBATE.
I GAVE A TALK ON IT A FEW MONTHS
AGO AND THE DIFFERENCE BETWEEN
DIRECT AND INDIRECT AND I'LL TRY
TO DO IT IN ONE SENTENCE.
BASICALLY THE IDEA IS THAT WHEN
YOU'RE ASSESSING THE PROSPECT OF
BENEFIT TO THE INDIVIDUAL IN A
STUDY IN ORDER TO DECIDE WHETHER
OR NOT THE RISK OF THE STUDY ARE
JUSTIFIED, MANY PEOPLE ARGUE THE
ONLY BENEFIT YOU SHOULD BE
MAKING THE COMPARISON WITH IS
THE DIRECT POTENTIAL BUT DIRECT
BENEFIT OF THE INTERVENTION AND
TESTING.
THERE'S LOTS OF OTHER BENEFITS
DESCRIBED FROM PARTICIPATING
RESEARCH.
ONE IS CONTRIBUTING TO THE GOOD.
PEOPLE LIKE TO DO THAT AND TALK
ABOUT THAT.
SOME IS KINSHIP BENEFITS BECAUSE
THEIR BEST FRIEND OR RELATIVE
HAD SOMETHING OR THEY'RE PASSING
IT ON TO THEIR CHILDREN.
SOMETIMES IT'S I HAVE ACCESS TO
DR. TAYLOR AT THE NIH AND I WANT
TO GO TO THAT PERSON AND THAT'S
A BENEFIT TO ME EVEN IF I DON'T
GET DIRECT BENEFIT FROM THE
INTERVENTION.
THE DIFFERENCE REALLY IS WHAT IS
PERCEIVED TO BE A BENEFIT BY A
NUMBER OF PEOPLE AND WHAT'S
ALLOWABLE FOR MAKING THE
ASSESSMENT OF WHETHER THE RISKS
ARE JUSTIFIED.
>> WE'LL NEED TO GO TO OUR NEXT
SPEAKER.
I CAN ADDRESS YOUR QUESTION
AFTER THE SESSION.
THANK YOU THOUGH FOR THE
QUESTIONS IN THE ROOM AND I DID
SEE PEOPLE THAT SENT IN QUESTION
AND ANSWER THEM IN NON-REAL TIME
AND FOR THOSE WHO ARE HAVING
TROUBLE FINDING WHERE TO POSE
QUESTIONS, I HAVE A PLACE -- I
WILL HAVE A PLACE EACH DAY ON
THE DISCUSSION BOARD WHERE YOU
CAN ASK QUESTIONS AND YOU DIDN'T
HAVE A CHANCE TO VIEW THE FIRST
PART YOU CAN GO TO THE POWER
POINT AND THERE'S INSTRUCTIONS
HOW TO DO IT.
SO WITHOUT ANY MORE DELAY, IT IS
MY GRATE PLEASURE TO INTER --
GREAT PLEASURE TO INTRODUCE OUR
NEXT SPEAKER TO TALK TO US ABOUT
THE HISTORY OF RESEARCH ETHICS.
THERE'S NO BETTER PERSON TO DO
IT THAN SUSAN LEADERER.
SHE'S THE RONALD L. NUMBERS
PROFESSOR AT THE UNIVERSITY OF
WISCONSIN SCHOOL OF MEDICINE.
SHE SPENT TIME AT BOTH YALE AND
PENN STATE.
SHE'S THE AUTHOR OF ONE OF THE
KEY BOOKS IN THE HISTORY OF
HUMAN EXPERIMENTATION CALLED
SUBJECTED TO SCIENCE, HUMAN
EXPERIMENTATION IN AMERICA
BEFORE THE SECOND WORLD WAR.
I HAVE A COPY ON MYSELF I'M
HAPPY TO LET YOU BORROW IT AND
WORKING ON A BOOK ON COREPOREAL
PHILANTHROPY.
>> I HOPE EVERYONE CAN HEAR ME.
>> WE CAN.
>> PERFECT.
HAPPY TO BE WITH YOU VIRTUALLY
FROM BEAUTIFUL, WISCONSIN AND
I'M GOING TO TALK TO YOU ABOUT
HOW WE GOT TO THIS PLACE IN
TERMS OF UNDERSTANDING THE
ETHICS OF CLINICAL
EXPERIMENTATION AND WHY DO WE
HAVE THE RULES FOR RESEARCH NOW
AND PREVIOUSLY AND SUGGEST TO
YOU IN A RAPID FASHION THAT A
LOT OF U.S. HEALTH POLICY IN THE
20th CENTURY OCCURRED AS A
RESPONSE TO SCANDAL AND TRAGEDY.
SOME MAY BE AWARE IN THE EARLY
20th CENTURY THERE WAS
CONSIDERABLE CONCERN OVER DRUGS
AND THERE WERE CONCERNS OF THE
SAFETY OF THE FOOD AND MEAT
SUPPLY.
SOME MAY REMEMBER THERE WAS A
QUESTION OF THE SAFETY OF THE
FOOD SUPPLY RESULTED IN THE
FIRST FEDERAL REGULATION IN THIS
REGARD.
THERE WAS AN ELIXIR TRAGEDY THAT
LED GREATER REGULATION IN THE
FOOD DRUG AND COMETIC ACT.
THE THERE WAS A DRUG AND TRYING
TO MAKE IT MORE PALATABLE TO
CHILDREN AND 107 PEOPLE DIED AS
A RESULT OF THIS.
AND THERE WERE CONCERNS ABOUT
COSMETIC AND DIETARY DRUGS THAT
BLINDED PEOPLE OR MASCARA, FOR
EXAMPLE, THAT CAUSED WOMEN TO
LOSE THEIR EYESIGHT.
CONGRESS PASSED A MAJOR REVISION
OF FOOD DRUG AND COSMETICS IN
1938.
THERE WERE MAJOR CHANGES IN THE
LAW THAT CALLED FOR REGULATION
AND TEST OF SAFETY BEFORE DRUGS
COULD BE RELEASED TO THE MARKET.
IN THE 1960s, I'M SURE YOU'RE
AWARE OF THE SULFANALMIDE AND
THERE WAS USE OF THE DRUG BEFORE
IT WAS RELEASED IN EUROPE AND
LED TO AN AMOUNT THE WORK OF
FRANCIS KELSEY IN THE FDA WAS
CRITICAL TO THIS AND FOR THE
FIRST TIME FDA COULD DEMAND
SCIENTIFIC DATA TO ENSURE DRUGS
WERE NOT ONLY SAFE BUT
EFFECTIVE.
AND THERE WAS REGULATION OF
ANIMAL WELFARE FOR LABORATORY
USE.
FOR OVER 60 YEARS, CONGRESS
CONSIDERED SUCH LEGISLATION AND
THE TIPPING POINT CAME IN
FEBRUARY OF 1966 WHEN A PHOTO
ESSAY IN LIFE MAGAZINE
DEMONSTRATED THE DIRE CONDITIONS
IN WHICH ANIMALS WERE KEPT IN
THE CONDITIONS BEFORE THE
LABORATORY AND THE FIRST
INVESTIGATION WAS THE ANIMAL
FEDERAL WELFARE ACT AND IN 1974
THE FIRST FEDERAL LEGISLATION
THE NATIONAL RESEARCH ACT WAS
PASSED IN 1974 AFTER THE
REVELATION OF THE TUSKEGEE
SYPHILIS STUDY WHICH I'M SURE
MANY ARE FAMILIAR.
IT'S MY OPPORTUNITY TO SORT OF
SAY EVEN BEFORE THE TUSKEGEE
SYPHILIS STUDY WAS PUBLIC THERE
WERE NAZI EXPERIMENTS.
THE USE OF HUMAN SUBJECTS IN
RESEARCH AND THE CONCERN ABOUT
THE ETHICAL USE OF HUMAN
SUBJECTS WAS MUCH OLDER.
IN 1900 THE UNITED STATES
CONGRESS ACTUALLY CONSIDERED A
BILL A LAW THAT WOULD HAVE
REQUIRED INVESTIGATORS TO
DISCLOSE IN ADVANCE THE PURPOSE
AND PROCEDURES OF ANY
NON-THERAPEUTIC EXPERIMENT
INVOLVING HUMAN BEINGS AND IN
THE LEGISLATION WHICH WAS NOT
ADOPTED, HOWEVER, THEY WERE
PARTICULARLY INTERESTED IN
BANNING EXPERIMENTS THAT WOULD
HAVE INVOLVED PEOPLE DEEMED
UNABLE TO CONSENT BANNING
INFANTS AND PEOPLE UNDER 21 AND
PREGNANT WOMAN DEEMED INCAPABLE
OF MAKING INFORMED DECISIONS AT
THAT TIME.
THERE WERE IN FACT EXPERIMENTERS
WHO WERE CONCERNED ABOUT THEIR
OWN RESPONSIBILITIES AS
RESEARCHERS AND FOR THE WELFARE
OF THEIR SUBJECTS.
I WOULD POINT TO THE U.S. ARMY
YELLOW FEVER BOARD IN CUBA.
THIS WAS AFTER THE TAKING OVER
THE ISLAND AND YELLOW FEVER WAS
A TERRIBLE PLAGUE ON ISLANDERS
AND GREAT CONCERN IN
UNDERSTANDING HOW TO DO
EXPERIMENTS AND THEY TRIED TO
TRANSMIT YELLOW FEVER BETWEEN
PEOPLE AND WERE CONCERNED ABOUT
THE WELFARE OF THEIR SUBJECTS
AND RESPONSIBILITIES AND THERE
WERE WRITTEN PERMISSION FORMS --
I KNOW YOU CAN'T READ THAT BUT
ONE THING I WAS INTERESTED IN IS
THEY WERE AVAILABLE IN BOTH
ENGLISH AND SPANISH FOR NEWLY
ARRIVED IMMIGRANT AND THE
DOCUMENT WARNED OF DANGER TO
LIFE BY PARTICIPATING IN THE
EXPERIMENTS.
PROMISED GOOD MEDICAL CARE IN
THE ARMY HOSPITAL AND ALSO
DISCUSSED COMPENSATION.
AND THERE WERE $200 IF DEATH
OCCURRED AND THANKFULLY IN THIS
SET OF STUDIES, NO ONE DIED AS A
RESULT.
AGAIN, THERE WAS A ROBUST
HISTORY I'LL JUMP FOR REASONS OF
TIME TO WORLD WAR II WHICH WAS
AN EXTRAORDINARILY IMPORTANT
TRANSITION MOMENT AND THERE'S
UNPRECEDENTED FEDERAL FUNDING
RELATED TO THE WAR EFFORT FOR
THE F.D.R. OFFICE FOR SCIENTIFIC
RESEARCH AND DEVELOPMENT.
THIS WAS A WATERSHED MOMENT.
FUNDING NEW RESEARCHERS FOR
EXAMPLE, THEY WERE INTERESTED IN
THE AFFECTS OF COLD WATER, HIGH
ALTITUDE AND DESALINIZATION
STUDIES FOR PILOTS AND THE
SEARCH FOR UNIVERSAL BLOOD
SUBSTITUTE AND MALARIA,
GONORRHEA AND HEPATITIS.
TO REMIND YOU THE KINDS OF
STUDIES.
THIS WAS DONE IN GALVESTON BAY
AND THEY WERE KEPT ALIVE LONG
ENOUGH AND RESCUES TO DESALINATE
WATER.
MALARIA RESEARCH IN U.S. PRISONS
WHERE PRISONERS VOLUNTEERED TO
INFECTED WITH LOADED MOSQUITOS
SO THEY CAN STUDY THE BEST WAY
TO AVERT IT AND THE SEARCH FOR A
VACCINE TO PREVENT IT.
THERE WERE SIMILAR MILITARY
MEDICAL RESEARCH AGENDA THAT THE
NAZIS HAD.
THEY'RE FIGHTING IN SIMILAR
FIELDS AND YET WE KNOW THE NAZI
RESEARCHERS CARRIED OUT THEIR
EXPERIMENTS TO MUCH GREATER MORE
BRUTAL EXTENT OFTEN RESULTING IN
DEATH IN THE CONCENTRATION CAMP
STUDIES.
SOME MAY BE FAMILIAR THE FIRST
EXPERIMENTS UNDERTAKEN ON BEHALF
OF THE GERMAN AIR FORCE WERE
HELD IN A CONCENTRATION CAMP AND
THEY WERE THRUST INTO COLD WATER
UNTIL THEY DIED IN AN EFFORT TO
STUDY HOW LONG SOMEONE COULD
SURVIVE.
THEY WERE INTERESTED IN
DEVELOPING VESTS THAT WOULD KEEP
PEOPLE ALIVE LONGER SO THEY
COULD BE RESCUED.
THEY WERE INTERESTED IN STUDYING
EFFECTS OF THE BEST WAY TO
REWARM PEOPLE WHO HAD BEEN IN
FREEZING WATER FOR LENGTHY
PERIOD OF TIME.
AND IN THE STUDIES DEATH WAS AN
INPUT.
THEY WANTED TO HAVE THE ABILITY
TO STUDY POSTMORTEM CHANGES IN
THE BRAIN DUE TO CHANGES IN
OXYGEN CONCENTRATION.
THEY WERE INTERESTED IN SEEING
HOW LONG PEOPLE COULD SURVIVE IF
THEY DRANK SEA WATER, IF THEY
WERE ABLE TO DESALINATE THE
WATER.
IN THIS CASE THEY USED INMATE IN
STUDIES TO MAKE THE SEA WATER
POTABLE AND JUST A LITTLE BIT
THIS COMES FROM TESTIMONY ABOUT
THE SEA WATER EXPERIMENTS IN
WHICH GERMAN, CZECH AND POLISH
WERE RECRUITED FOR WHAT WAS
DESCRIBED AS A CLEAN-UP WORK
DETAIL.
IN THE INTEREST OF BETTER
RATIONS AND BETTER WORKING
CONDITIONS, THEY AGREED TO GO
AND THEY FOUND OUT THEY WERE
SPLIT INTO FIVE DIFFERENT GROUPS
AND SOME WERE GIVEN NO WATER AT
ALL TO SEE HOW LONG THEY WOULD
SURVIVE AND DIESEL NA--
DESALINATED SEA WATER AND
ANOTHER EXPERIMENT WITH THE SEA
WATER AND WE KNOW FROM TESTIMONY
OF PEOPLE LIKE HIM WHEN THE
INMATES WERE UNABLE TO COMPLY
WITH THE BRUTAL EXPERIMENTAL
REGIMENT THEY WERE FORCED AND
HELD DOWN AND PHYSICALLY GIVEN
THE SALT WATER FOR EXAMPLE AND
THAT THEY ALSO UNDERWENT WITHOUT
ANESTHESIA SUCH AS LIVER
PUNCTURES AND SPINAL PUNCTURES
SO THEY COULD STUDY SALINATE.
AND HERE POLISH WOMEN WERE
REFERRED TO EBB ET GIRLS BECAUSE
OF THEIR EXPERIMENTAL STATUS AND
THE RESEARCHERS CREATED WOUNDS
IN AN EFFORT TO CREATE THE
STANDARDIZED WOUND WITH
INCISIONS, INFECTED THEM WITH
BACTERIA, DIRT AND SLIVERS GLASS
IT STUDY THE BEST WAY TO TREAT
STANDARDIZED WOUNDS.
IN THE UNITED STATES THERE WAS
ALSO INTEREST IN CREATING A
STANDARDIZED WOUND BUT THIS WAS
DONE ON ANIMAL SUBJECTS BOTH
DOGS AND PIGS WERE USED TO LOOK
AT THE EFFICACY OF PENICILLIN
INTRODUCED IN 1941 IN THE U.S.
YOU'RE PERHAPS ALL FAMILIAR
AFTER WORLD WAR II THERE WERE A
SERIES OF TRIALS OF HIGH-RANKING
NAZIS AND IN 1946 A
U.S. MILITARY TRIBUNAL TRIED 23
HIGH-RANKING NAZI MEDICAL
PERSONNEL FOR THEIR CRIMES
AGAINST HUMANITY IN A COURT IN
NUREMBERG.
IT'S CALLED THE NUREMBERG
DOCTORS TRIAL OR THE UNITED
STATES AGAINST KARL BRANDT ET
AL. AND HE WAS HITLER'S PERSONAL
PHYSICIAN AND OTHER HIGH RANKING
DOCTORS INCLUDING ONE FEMALE
PHYSICIAN WHO PROV PRESIDED OVE
CARE OF INMATE AT ONE
CONCENTRATION CAMP.
WHAT STANDARDS SHOULD BE USED TO
JUDGE THESE EXPERIMENTS?
WERE THERE INTERNATIONAL
STANDARDS?
AND THERE WERE FINDINGS WHAT WAS
ETHICAL TO DO BUT LITTLE IN THE
WAY OF FORMAL LAW AND
REGULATION.
THE DEFENSE ATTORNEYS THAT
REPRESENTED KARL BRANDT SAID
THERE WAS LITTLE DIFFERENCE FROM
THE GERMAN PRACTICE USING
CONCENTRATION CAMP INMATES
BECAUSE IN THE UNITED STATES
RESEARCHERS WERE USING PRISONERS
DURING WARTIME.
PRISONERS PARTICIPATED IN A
SERIES OF STUDIES INVOLVING
MALARIA, SEXUALLY TRANSMITTED
DISEASES AND OTHER THINGS.
OF THE TRIAL OF THE NAZI DOCTORS
THE DEFENSE ATTORNEYS USED AS
EVIDENCE THE ISSUE OF LIFE
MAGAZINE FROM 1945 THAT SHOWED A
PRISON WARD IN ILLINOIS THAT
INVOLVED DELIBERATELY INFECTING
PRISONERS WITH VERY SERIOUS
STRAINS OF MALARIA BUT AGAIN
THOUGH THEY BOTH USED PRISONERS
THEY USED THEM UNDER DIFFERENT
CONDITIONS.
AND THERE'S JUDGES THAT HAD NO
MEDICAL TRAINING AND HE
INFLUENCED -- THERE WERE OTHERS
BUT HE INFLUENCED THE CREATION
OF A DOCUMENT THE JUDGES CALLED
PERMISSIBLE MEDICAL EXPERIMENTS
WHICH HAS COME TO BE KNOWN AS
THE NUREMBERG CODE.
IT'S CONDITIONS HOW IT WAS
PERMISSIBLE, ETHICAL TO USE
HUMAN SUBJECTS IN RESEARCH.
IT'S MOST OFTEN CITED AND I HOPE
YOU GET TO READ THE NUREMBERG
CODE.
IT'S THE FIRST PRINCIPLE THE
VOLUNTARY CONCEPT OF THE HUMAN
SUBJECT IS ABSOLUTELY ESSENTIAL.
IT GOES IN A LENGTHY PERIOD ON
TO DOCUMENT THE CONDITIONS UNDER
WHICH AN INDIVIDUAL CAN GIVE
CONCEPT.
IT REQUIRES PRIOR ANIMAL
EXPERIMENTATION.
THE GOAL IS TO AVOID ALL
UNNECESSARY SUFFERING AND
THERE'S NO REASON TO THINK DEATH
WILL RESULT AND RISK SHOULD NOT
EXCEED BENEFIT AND RESEARCH
SHOULD ONLY BE CONDUCTED BY
SCIENTIFICALLY QUALIFIED
PERSONNEL NOT BY SOLDIERS OR BY
LAY PEOPLE WITHOUT ANY TRAINING
WHATSOEVER.
SEVEN WERE ACQUITTED AND SEVEN
RECEIVED DEATH SENTENCES AND
NINE GOT 10 YEARS TO LIFE
IMPRISONMENT.
THE OTHERS HAD THEIR SENTENCES
REDUCED.
WHAT DID THE NUREMBERG CODE MEAN
TO MEDICAL RESEARCHERS?
ON THE ONE HAND THERE'S A GOOD
ARGUMENT AMERICAN RESEARCHERS
WERE AWARE OF IT.
THE JOURNAL OF SCIENCE PUBLISHED
A CODE AND A SYMPOSIUM FOR THE
WAY AMERICAN MEDICAL RESEARCH
WORKED.
WE KNOW THE SECRETARY OF DEFENSE
REQUIRED OR SIGNED INTO MILITARY
REGULATION THAT IT WAS TO BE
USED FOR RESEARCH AT THE ARMED
FORCES.
AT THE SAME TIME IT WAS
CLASSIFIED AS TOP SECRET.
SOME INVESTIGATORS WHO WANTED
ACCESS TO THIS INFORMATION WERE
THWARTED AT THE FACT OF THAT
CLASSIFICATION.
AND IN AMERICAN MEDICAL RESEARCH
THE RESEARCHERS WERE ALREADY
VERY CAREFUL ABOUT THE SAFETY
AND WELFARE OF THEIR SUBJECTS.
SO PUT BOLDLY WHAT WOULD THEY
HAVE IN THEIR OVERCOAT?
NOT AT THAT TIME.
AND I JUST WANT TO REMIND YOU IN
THE 1950s, AMERICAN MEDICAL
RESEARCH WAS ASSOCIATED WITH
VOLUNTEERS.
A LONG TRADITION OF
EXPERIMENTATION AND THERE WERE
TREMENDOUS ADVANCES DURING THE
SECOND WORLD WAR IN MEDICINE
THAT THEY HOPED FOR GREAT
ADVANCES IN MEDICINE AS A RESULT
OF ONGOING EXPERIMENTATION SOME
MAY BE FAMILIAR WITH THE POLIO
EPIDEMIC RANGE WAS 1952 AND ONE
OF THE GREAT ADVANCES BY THE
GROUP AT THE UNIVERSITY OF
PITTSBURGH WAS A TEST INVOLVING
1.8 AMERICAN CHILDREN AGES 6 AND
7 OF THE POLIO VACCINE AND ALSO
PARENTS HAD TO REQUEST THEY'RE
CHILD PARTICIPATE IN THE STUDY
AND ACTUALLY SIGN A FORM -- NOT
INFORMED CONSENT BUT SIGNED A
PARENTAL REQUEST FORM KNOWING
THAT THEIR CHILDREN WOULD EITHER
RECEIVE A VACCINE OR A PLACEBO
VACCINE.
LET ME MAKE THE POINT MOST
PERSON RESEARCHERS REGARD THE
NUREMBERG CODE AS UNWORKABLE AND
SET THE BAR TOO HIGH FOR PEOPLE
WHO COULD PARTICIPATE IN
CLINICAL RESEARCH.
IT WOULDN'T ALLOW EXPERIMENTS ON
CHILDREN WHICH WERE AN IMPORTANT
POPULATION FOR DISCOVERING
VACCINES.
IT WOULD NOT ALLOW EXPERIMENT ON
OTHER POPULATIONS DEEMED -- WHO
WOULD BENEFIT FROM SUCH
EXPERIMENTATION.
AND THERE WAS A GREAT EFFORT TO
DEVELOP A MUCH MORE WORKABLE
CODE ONE THAT WOULD PROTECT
SUBJECTS AND ALLOW RESEARCH TO
CONTINUE.
THIS IS THE 1964 DECLARATION OF
HELSINKI DIRECTING DOCTORS AND
IT CONTINUES TO BE USED TODAY
AND TO BE REFERRED TO IN A
NUMBER OF NATIONS AS GUIDING
PRINCIPLES FOR RESEARCH.
I WILL SAY AGAIN THIS WAS DEEMED
BY RESEARCHERS AS MUCH MORE
AMENABLE TO IMPROVING OR
ADVANCING BIO MEDICAL KNOWLEDGE.
THIS SLIDE REMINDS YOU THAT THE
REGULATION AND EXPECTATIONS OF
CLINICAL RESEARCH CHANGE
OVERTIME AND THIS EFFORTS BY THE
WORLD MEDICAL ASSOCIATION TO
CREATE SORT OF THE BEST
PRACTICES GOING FORWARD.
LET ME RETURN TO MY ONGOING
RESPONSE TO TRAGEDY IN HUMAN
EXPERIMENTATION.
NO LONGER FAITH IN MEDICAL
RESEARCHERS AND IN 1966 I'LL
REFER TO IS THE DISCUSSION AND
CHALLENGES IN HUMAN
EXPERIMENTATION AND TAPPED BY
THE ABOWS OF HUMAN SUBJECTS
ESPECIALLY IN THE TUSKEGEE
SYPHILIS STUDY.
SO HENRY BEACHER WAS A PROFESSOR
OF ANESTHESIA RESEARCH AT
HARVARD MEDICAL SCHOOL AND
CONVENE THE HARVARD COMMITTEE
FOR TRANSPLANTATION AND OTHER
ASPECTS.
IN 1966 HE PUBLISHED AN ARTICLE
IN THE NEW ENGLAND JOURNAL OF
MEDICINE IF YOU HAVE THE TIME I
ENCOURAGE YOU TO READ IT.
IT'S A VERY SHORT ARTICLE BUT
HAD FAR REACHING AFFECTS AND
DESCRIBED THE TREMENDOUS GROWTH
OF THE HUMAN CLINICAL RESEARCH
AND QUESTIONED RESEARCH OF
QUESTIONABLE RESEARCH PRACTICES
AND OUTLINED 22 EXAMPLES.
THE POINT IS THIS WASN'T A
FRINGE PROBLEM OR SOMEBODY IN
THEIR GARAGE BUT FROM MAINSTREAM
RESEARCHERS AND FUNDERS OF
BIOMEDICAL RESEARCH.
HE MADE REFERENCE TO 22
PUBLISHED ARTICLES AND FIVE FROM
THE NEW ENGLAND JOURNAL OF
MEDICINE, FIVE FROM THE JOURNAL
OF CLINICAL INVESTIGATION AND
JAMA CIRCULATION AND SO FORTH.
HE WAS CONCERNED ABOUT YOUNG ERS
BECAUSE OF THE ONCE PRECEDENTED
ATTENTION TO MEDICAL RESEARCH IN
THE 1940s THAT HAD AN UN --
INFLUX AND TALK ABOUT
RESPONSIBILITY FOR THE
PROTECTION AND WELFARE OF THEIR
PATIENTS AND HUMAN SUBJECTS.
I WANTED TO POINT OUT THE PEOPLE
BEACHER WAS CONCERNED WITH AND
THE LANGUAGE IS IN QUOTATION
BECAUSE IT'S THE LANGUAGE OF THE
DAY IN THE 1960s AND THE
EXPERIMENTS HE IDENTIFIED AS
PARTICULARLY QUESTIONABLE
INVOLVED SO-CALLED MENTALLY
DEFECTIVE CHILDREN AND THE
ELDERLY AND SENILE AND CHARITY
PATIENTS, THE TERMINALLY ILL,
ALCOHOLICS AND CHILDREN OF THE
NEWLY OPENED NIH CLINICAL
CENTERS AND TWO WELL KNOWN
EXAMPLES CONSIDERED ABUSES AS
SCANDALS IN THE 1960s ONE WAS
THE WILLOWBROCK INSTITUTION IN
STATEN ISLAND FOR CHILDREN AT A
TIME WHEN VIRTUALLY ALL PARENTS
WERE INFORMED THEY SHOULD
INSTITUTIONALIZE SUCH CHILDREN.
HEPATITIS WAS RIFE AT THE
INSTITUTION AND THE
INVESTIGATORS WANTED TO STUDY
HOW TO PREVENT AND TREAT THIS
DISEASE AND SO NEWLY ADMITTED
CHILDREN WHOSE PARENTS GAVE
CONSENT AT THIS TIME THEY WERE
GIVEN MILK SHAKES WITH LIVE
HEPATITIS AND THEN PLACED IN THE
MEDICAL WARD FOR THE PHYSICIANS
AND THEIR EXPERIENCE WITH THE
DISEASE STUDIED.
AND THEY CONTINUED TO DEFEND THE
STUDIES.
HE WAS A PIONEER IN HAVING IN
ENLISTING PARENTS IN THEIR
RESEARCH BY INFORMING THEM WHAT
WOULD HAPPEN AND THE CARE THEY
WOULD RECEIVE IF THEIR CHILDREN
INDEED FELL ILL BUT THERE
CONTINUED TO BE ISSUES ABOUT
COERCION AND WAS THE ONLY WAY TO
GET YOUR CHILD IN THE
INSTITUTION AND ALSO ABOUT STUDY
DESIGN.
THE OTHER NOTORIOUS EXAMPLE FROM
THE 1960s AND IDENTIFIED WAS OF
THE JEWISH DISEASE HOSPITAL CASE
AND AGAIN NOTE THE FUNDERS, THE
PUBLIC HEALTH SERVICE AND THE
AMERICAN CANCER SOCIETY INVOLVED
IN THE MOVEMENT OF CANCER AND
BODIES AND INVOLVED INJECTING
LIVE CANCER CELLS INTO ELDERLY
PATIENTS WITHOUT THEIR KNOWLEDGE
AND EXPLAINED THEY DID NOT SEEK
TO EXPLAIN THE NATURE OF THE IN
SECTIONS TO THESE ELDERLY IN
SOME CASES DEMENTED PATIENTS AND
I'LL POINT OUT THE LEAD
INVESTIGATOR WHO WAS ON THE
STAFF OF KETTERING, GAVE A KIND
OF DISASTROUS INTERVIEW WITH
SCIENCE MAGAZINE IN 1964 WHEN HE
WAS ASKED WHY HE DEVIATED FROM
THE TRADITION OF USING HIS OWN
BODY BEFORE EXPERIMENTING ON
OTHERS AND HE SAID LET'S FACE IT
THERE'S RELATIVELY FEW CANCER
RESEARCHERS AND SEEMS STUPID TO
TAKE A LITTLE RISK.
THIS DID NOT END WELL FOR HIM
AND HE HAD HIS LICENSE SUSPENDED
FOR A SHORT TIME.
IT WAS THE REVELATION OF THE
TUSKEGEE STUDY MORE THAN ANY
OTHER SINGLE STUDY OR EXAMPLES
THAT COMPELLED CONGRESS TO ADOPT
THE FIRST FEDERAL LEGISLATION
SEEKING TO PROTECT THE HUMAN
SUBJECTS OF BIOMEDICAL RESEARCH.
THE STUDY INVOLVED A POPULATION
OF AFRICAN AMERICAN MEN IN RURAL
ALABAMA WHERE THE INCIDENCE OF
SYPHILIS WAS EXTRAORDINARILY
HIGH.
IT WAS PART OF AN EFFORT AT THE
PUBLIC HEALTH SERVICE TO IMPROVE
OR TO TAKE UP THE STUDY OF SEX
HI -- SEXUALLY TRANSMITTED
DISEASES.
THE SURGEON GENERAL PUBLISHED AN
INFLUENTIAL BOOK IN 1937, SHADOW
ON THE LAND AND OVERSAW MUCH OF
THE STUDY THROUGH 1948 WHEN HE
STEPPED DOWN BUT THIS COMES FROM
HIS BOOK SHOWING THAT IN ALABAMA
WHERE THE TUSKEGEE STUDY BEGAN
HAD A 35% OF THE AFRICAN
AMERICAN POPULATION WAS
REPORTEDLY INFECTED WITH
SYPHILIS SO IT WAS A PUBLIC
HEALTH EMERGENCY OF HIGH ORDER
AND ONE THEIR REASONS WHY THEY
SELECTED THAT GROUP OF
INDIVIDUALS FOR WHAT WAS
INITIALLY A SHORT-TERM STUDIO.
THE STUDY DEVOVLEKED TO UNTIL
PEOPLE DIED OF SYPHILIS OVER THE
COURSE THEIR NEXT 40 YEARS.
THEY WERE SENT AND AS THE STUDY
MOVED FROM TREATMENT WHAT WAS
GOING TO BE A TREATMENT STUDY TO
A STUDY IN NATURE AND AMONG
THOSE WHO SOME OF THE INITIAL
TESTING ON THE POPULATION SO
THEY COULD FOLLOW THE PROGRESS
IN THE BODY OF UNTREATED
SYPHILIS AND DID THIS BY
DECEIVING THE MEN WHO WOULD BE
STUDY PARTICIPANTS WITH A LAST
CHANCE FOR SPECIAL TREATMENT FOR
THEIR BAD BLOOD.
AMONG THE LAST SPECIAL FREE
TREATMENTS WAS LUMBAR PUNCTURE
WHICH WAS AN ENTIRELY DIAGNOSTIC
PROCEDURE AND ONE IN WHICH THE
MEN SUFFERED GREATLY AND REFUSED
IN SUBSEQUENT YEARS TO EVER
UNDER GO SPINAL PUNCTURE AGAIN.
WHAT THE PUBLIC HEALTH SERVICE
DID WAS TO REFUSE THE DRAFT
BOARD OF MEGAN COUNTY TO CALL UP
MEN IN STUDY BECAUSE THEY WERE
DRAFTED AND IF THEY HAD BEEN
DRAFTED THEIR SYPHILIS WOULD
HAVE BEEN TREATED BY THE ARMY.
THE STUDY INVOLVED AN AFRICAN
AMERICAN NURSE TAXED WITH
GETTING PERMISSION FROM THE MEN
FOR THE POSTMORTEM AFTER THEIR
DEATHS.
SHE FOUND IT EASIER TO DO IN A
BURIAL STIPEND WAS PROVIDED AND
PUBLISHED AN ARTICLE IN 1953
DESCRIBING ONE REFUSAL IN 140
REQUESTS.
1954 LITERATURE MEN ARE
CONSIDERED SOCIAL VOLUNTEERS
WITH BURIAL INSURANCE.
IN 1957 THERE'S AN EFFORT BY
INVESTIGATORS TO GIVE MEN A
CERTIFICATE SIGNED BY THE
SURGEON GENERAL AND A DOLLAR FOR
EACH YEAR THEY SERVED IN THE
STUDY, SO $25.
THERE WAS A BLUE RIBBON PANEL TO
ALONG WHETHER IT SHOULD
CONDITION SHOULD BE CONTINUED
AND THE MEN OFFERED TREATMENT
BUT THE STUDY CONTINUED UNTIL
1972 WHEN IT WENT OUT OVER THE
WIRE SERVICE AND CREATED PUBLIC
FUROR.
THE LEGISLATION WAS PASSED IN
1974 AND CONTINUES TO THIS DAY
THOUGH IT HAS BEEN AMENDED.
CREATED A NATION CONVENTION TO
STUDY THE MORAL ISSUES OPPOSED
BY HUMAN EXPERIMENTATION AND
FEDERAL REGULATIONS FOR IRBs AND
WRITTEN INFORMED CONSENT.
I WILL SAY THAT THERE REMAINED
PERSISTENT STORIES ABOUT THE
TUSKEGEE SYPHILIS STORY AND THE
GOVERNMENT INVESTIGATORS
DELIBERATELY INFECTED THE MEN.
THERE'S NO EVIDENCE WHATSOEVER
THAT THE INVESTIGATORS SOUGHT TO
CHOOSE MEN WHO WERE ABLE TO DATE
THEIR INFECTION FOR AT LEAST
FIVE YEARS.
HOWEVER, CONCERNS ABOUT THE
TREATMENT PARTICULARLY OF
MINORITY PARTICIPANTS IN
RESEARCH.
IN FACT IN THE EARLY DAYS OF
AIDS RESEARCH, MANY MAINSTREAM
OBSERVERS WERE ASTONISHED TO
LEARN AS THE EDITORIAL IN THE
NEW YORK TIMES FROM 1992
SUGGESTS THAT AFRICAN AMERICANS
MAY BE SUSPICION OF A GOVERNMENT
EFFORT OR EVEN VACCINE TO TREAT
HIV BECAUSE OF THE PRIOR
EXPERIENCE AND WHAT WAS DONE IN
THE TUSKEGEE STUDY.
I PUT THE SLIDE IN BRIEFLY TO
CALL YOUR ATTENTION TO THE FACT
THAT OVER THE YEARS THERE'S BEEN
OTHER SIGNIFICANT REVELATIONS.
ONE WAS IN 1994 AND 1995 WHEN
THE FACT THAT THE HUMAN -- THE
FEDERAL GOVERNMENT HAD STUDIES
WITH IONIZING RADIATION IN THE
UNITED STATES AND A COMMISSION
WAS CREATED.
THERE WAS A PRESIDENTIAL APOLOGY
FOR THOSE INDIVIDUALS WHOSE
LIVES HAD BEEN DARKENED BY THE
SHADOW OF THE ATOM AND THE FACT
THE FEDERAL GOVERNMENT FUNDED
RESEARCH INVOLVING THEIR BODIES
OFTEN WITHOUT THEIR CONSENT OR
KNOWLEDGE.
THAT LED TO THE RECOGNITION THAT
THERE HAD BEEN NO APOLOGY TO THE
PARTICIPANTS THEIR TUSKEGEE
STUDY AND IN 1957 THE WHITE
HOUSE FORMALLY A -- 1997 WHITE
HOUSE OFFICIALLY APOLOGIZED WITH
THE PRESIDENT, VICE PRESIDENT
AND SURGEON GENERAL.
AGAIN THE REVELATION OF SCANDAL
AND TRAGEDY CONTINUED.
THE PUBLIC HEALTH SERVICE
TRAVELED TO GUATEMALA IN 1946
AND 1948 AND INFECTED THOUSANDS
OF GAUATEMGUATEMALANS AND THEY
APOLOGIZED FOR THE AMERICANS'
CONDUCT HERE.
THIS IS A STUDY IN WHICH THE
PUBLIC HEALTH SERVICE
INVESTIGATORS FUNDED BY NIH USED
SEX WORKERS IN AN EFFORT TO
TRANSMIT SYPHILIS AND GONORRHEA
GUATEMALAN SOLDIERS AND THEY
INFECTED THE INMATE OF MENTAL
HOSPITALS WITH SYPHILIS,
GONORRHEA AND OTHER STDs IN SOME
CASES WITH PUNCTURE AND INFECTED
1500 PRISONERS.
NOW, ONE IMPORTANT DIFFERENCE
HERE IN THIS STUDY IS BY 1946
THERE WAS PENICILLIN AND FROM
THE REFERENCE WE KNOW SOME OO%
OF THOSE INDIVIDUALS RECEIVED
PENICILLIN AS A TREATMENT.
THE GUATEMALAN STUDIES WERE
NEVER REVEALED AND THERE WAS
CORRESPONDENCE THAT BECAME
AVAILABLE BETWEEN THE
RESEARCHERS AND THIS PARTICULAR
QUOTE HAS OFTEN BEEN CITED, WE
COULDN'T DO SUCH AN EXPERIMENT
IN OUR OWN COUNTRY.
THAT'S THOMAS HERON IN 1948.
AND IF YOU HAVE INTEREST CONSULT
THE PRESIDENTIAL COMMISSION
STUDY REPORT, ETHICALLY
IMPOSSIBLE FROM SEPTEMBER 2011.
THIS IS THE HISTORY IN A QUICK
SNAPSHOT AND I THINK THE
CHALLENGE IS CLEAR AND WE ALL
FACE IT AS A SOCIETY AND
RESEARCHERS HOW BEST TO PROTECT
HUMAN SUBJECTS AND TO
SIMULTANEOUSLY ADVANCE MEDICAL
KNOWLEDGE.
SO THANK YOU.
I KNOW I'VE GONE LONG.
>>
[OFF-MIC]
>> I ASSUMED YOU WERE MAKING
THAT UP.
WE ALSO HAVE FOLKS OUT IN VIDEO
LAND WHO ARE ABLE TO ASK
QUESTIONS ON THE DISCUSSION
BOARD AND ALSO SEND US E-MAILS
AND FOR A REMINDER, WE HAVE A
TEN-MINUTE BREAK SORRY, A
15-MINUTE BREAK AFTER SUSAN'S
AVAILABLE FOR QUESTIONS.
SO I HAVE IN THE PAST BROUGHT
CANDY TO ENTICE PEOPLE TO ASK
QUESTIONS.
I MIGHT HAVE TO DO THAT AGAIN.
AND GIVEN THE LESSONS, WE DO
HAVE SOME EXAMPLES OF STUDIES
THAT HAVE GONE AWRY AS RECENTLY
AS JUST A COUPLE OF YEARS AGO.
IN TERMS OF EXPOSING HUMANS TO
RISKS THAT YOU AND I THINK THEY
SHOULDN'T BE EXPOSED TO.
AND I'M WONDERING ANY THOUGHTS
YOU MIGHT HAVE ON IS THIS JUST
ALWAYS GOING TO HAPPEN?
WE'VE LEARNED SO MUCH FROM
HISTORY BUT WE WILL CONTINUE TO
LEARN FROM CONTEMPORARY HISTORY
BECAUSE IT'S LIKELY TO CONTINUE
ON.
WE'RE ALL HUMANS I GUESS AS PART
OF THE CHALLENGE HERE.
>> THAT'S AN IMPORTANT QUESTION
AND ONE THING THAT'S SURPRISED
ME AS AN OBSERVER OF HOW THEY GO
ON IS THAT IT'S MY UNDERSTANDING
IF AN INVESTIGATOR CONDUCTS
PRIVATE RESEARCH IT MAY NOT BE
COVERED BY THESE FEDERAL
REGULATIONS.
IS THAT YOUR UNDERSTANDING AS
WELL, HOLLY?
>> YEAH.
IN GENERAL IF YOU ARE CONDUCTING
RESEARCH AT AN INSTITUTION THAT
RECEIVES FEDERAL MONEY LIKE MOST
ACADEMIC MEDICAL CENTERS, OR
YOU'RE IN THE PRIVATE SECTOR
PURSUING RESEARCH THAT YOU HOPE
TO BE SUBMITTING TO THE FDA FOR
MARKETING APPROVAL YOU'RE
REQUIRED TO HAVE IRB REVIEW.
BUT THAT DOESN'T MEAN
NECESSARILY THAT ALL RESEARCH IS
THEREFORE REVIEWED BY SOME SORT
OF INSTITUTIONAL REVIEW BOARD OR
RESEARCH ETHICS COMMITTEE.
WE WERE ACTUALLY JUST HAVING A
CONVERSATION THE OTHER DAY AFTER
A PRESENTATION THAT I MADE HERE
IN THE DEPARTMENT ABOUT THE
FOLLOWING COULD BE TRUE.
FOR EXAMPLE, IF I'M A PRIVATE
PHARMACEUTICAL COMPANY AND
INTERESTED IN DEVELOPING A NEW
DRUG, I KNOW I HAVE TO SUBMIT
RESEARCH THAT I WILL INCLUDE IN
MY MARKETING APPLICATION TO BE
REVIEWED BY AN IRB.
BUT MAYBE I DO A COUPLE OF
STUDIES BEFORE JUST TO MAKE SURE
I'M ON THE RIGHT TRACK AND THEN
I SUBMIT THE SIX FOLLOW-UP
STUDIES TO THE FDA FOR APPROVAL.
SO I DON'T THINK IT HAPPENS VERY
OFTEN BECAUSE I THINK AND I
DON'T KNOW IF THE PHARMACEUTICAL
COMPANY WAS CAUGHT DOING SUCH A
THING OR GOING TO A LOW AND
MIDDLE INCOME COUNTRY AND DOING
THE RESEARCH FIRST AND THEN
DOING IT IN THE UNITED STATES IT
PURSUE MARKETING APPROVAL I
THINK WE WOULD FIND OUT ABOUT IT
BUT IT IS POSSIBLE.
BUT THAT'S A SPACE IN WHICH
THERE COULD IN VIOLATIONS OF THE
FEDERAL REGULATIONS BECAUSE THEY
DON'T THINK THEY HAVE TO FOLLOW
IT.
>> I KNOW I WAS STRUCK BY
STUDIES THAT BECAME OR CAME TO
PUBLIC NOTICE INVOLVING AN
OFFSHORE HERPES VACCINE TRIAL
BUT BEFORE THEY MOVED OFFSHORE
THEY WERE CONDUCTING STUDIES AT
A UNIVERSITY AT ILLINOIS THAT
INVOLVED HAVING THE RESEARCH
PARTICIPANTS GOING TO THE
HOLIDAY INN.
IT STRIKES ME AND THE FACT THAT
IF THIS RECEIVED IT DIDN'T COME
TO PEOPLE'S ATTENTION AT THE
TIME I FIND BAFFLING.
>> I HAVE A COUPLE QUESTIONS
FROM THOSE OUT IN VIDEO LAND AND
HERE'S AN INTERESTING ONE.
ONE THAT I'M SURE YOU THOUGHT
ABOUT GIVEN THAT WE TALKED ABOUT
THESE EXPERIMENTS THAT IN
RETROSPECT WERE UNETHICAL EITHER
IN THEIR PLANNING, EXECUTION,
ETCETERA.
WHAT DO WE DO WITH THE
INFORMATION THAT WE GAINED FROM
THOSE RESEARCH PROJECTS?
SO THE UNETHICAL EXPERIMENTS
THAT HAPPENED DURING THE NAZI
ERA OR RESULTS FROM THE SYPHILIS
TRIAL OR FROM THE JEWISH CHRONIC
DISEASE HOSPITAL TRIAL?
WHAT DO WE AS THE RESEARCH
COMMUNITY SHOULD WE USE THE
INFORMATION?
>> THAT'S CERTAINLY SOMETHING I
THOUGHT ABOUT AND SURE SOMETHING
YOU THOUGHT ABOUT AS WELL.
I THINK THERE'S THREE POSITIONS.
ONE IS YOU USE THE INFORMATION
OR YOU USE THE INFORMATION BUT
CALL ATTENTION TO EXTRAORDINARY
TRAGIC OR SCANDALOUS CONDITIONS
IN WHICH IT OCCURRED.
I FIRST ENCOUNTERED THE DEBATE
WHEN I ATTENDED BACK IF THE '90s
A CONFERENCE ON NAZI MEDICAL
EXPERIMENT.
I WAS VERY MOVED WHEN A WOMAN
WHO HAD BEEN IN A STUDY MADE THE
CASE POWERFULLY NONE OF THAT
INFORMATION SHOULD BE USED GIVEN
HOW IT WAS -- AND THAT STAYS
WITH ME TO THIS DAY.
I'VE ALSO HEARD OTHER
CONCENTRATION CAMP INMATE MAKE
THE ARGUMENT IF WE CAN GET
REDEPARTMENTIVE -- REDEMPTIVE
VALUE AND WE SHOULD LOOK AT HOW
AND WHAT WAY INFORMATION GETS
INCORPORATED.
AND IT INVOLVED EXPLOITATION AND
THE PROGRESS OF FUTURE PATIENTS
WE'RE USING IT MINDFUL OF THAT
THERE'S PRESSURE TO MAKE SURE
THESE THINGS DON'T GET IN THE
LITERATURE BUT GET A BROADER
VIEW.
THAT'S WHY IT'S SO INTERESTING
IN THE CASE OF THE GUATAMALAN
STUDIES THEY DECIDED NOT TO
PUBLISH.
THAT'S A LONG ANSWER.
>> GREAT ANSWER AND I'LL POST A
LINK IN CANVAS THERE'S AN
ARTICLE EDITED FROM MANY YEARS
AGO THAT SHARES THE PERSPECTIVES
YOU SHARED AND TO HEAR FROM
SOMEONE IN AN EXPERIMENT AND
RESPECT AND TAKE IN THEIR VIEWS
ON HOW THE INFORMATION SHOULD BE
USED AND THERE ARE DIFFERENT
STORIES AND IT'S A REALLY GREAT
BOOK.
I'LL POST THAT.
ONE AND ALSO I'LL HIGHLIGHT THAT
YOU MENTION ED THE DECLARATION F
HEL -- HELSINKI THEY NEED TO
MAKE SURE THEY'RE REVIEWED.
ANY JOURNAL WILL REQUIRE DUKE A
LOT OF INSTITUTIONAL REVIEW
BOARD APPROVAL.
THANK YOU FOR JOINING US FROM
WISCONSIN AND HAVE A LOVELY REST
OF YOUR DAY.
>> THANK YOU SO MUCH.
THANK YOU.
>> OKAY.
WORD OF THE DAY, BELMONT.
WE HAVE NOW REACHED THE BREAK.
WE'LL DO THIS EVERY DAY WE HAVE
CLASS.
WE'LL HAVE A 15-MINUTE BREAK.
PLEASE REJOIN THE LINK AT 10:50
OR MOVE IT ON IN THE BACKGROUND
I'M GOING TO FINISH WITH
INSTITUTIONAL REVIEW BOARDS.
FEEL FREE TO BREAK.
JUST TO REMIND YOU THE WORD OF
THE DAY IS BELMONT.
AND YOU GET TO HAVE ME AS YOUR
LAST SPEAKER AND I'M GOING TO
TALK A BIT ABOUT INSTITUTIONAL
REVIEW BOARDS.
DR. GRADY INTRODUCED THE TOPIC.
IT'S ONE OF THE KEY BENCHMARKS
INDEPENDENT REVIEW AND I AM
GOING TO APOLOGIZE IN ADVANCE
AND SAY I HAVE A VERY DOMESTIC
PERSPECTIVE ON THE TOPIC.
THAT SAID I'M GUESSING EVERY
INSTITUTION THAT THOSE OF YOU
OUT THERE ARE AFFILIATED WITH
HAVE SOMETHING LIKE AN
INSTITUTIONAL REVIEW BOARD OR
RESEARCH ETHICS COMMITTEE WHERE
SOMEONE PROPOSING RESEARCH HAS
TO GO TO WITH THEIR PROPOSAL AND
IT IS REVIEWED AND APPROVED BY
THEM BEFORE IT CAN BE PUT INTO A
HUMAN SUBJECT.
SOMETIMES THAT'S A NATIONAL
BOARD OR A REGIONAL BOARD OR
SIMILAR TO THE MODEL WE HAVE
HERE IN THE U.S.
A BOARD THAT IS AFFILIATED WITH
THE ACADEMIC MEDICAL INSTITUTE
OR UNIVERSITY THAT THE
INVESTIGATOR IS PLANNING TO DO
THEIR RESEARCH AT.
WITH THAT, HERE'S MY DISCLAIMER
AGAIN IN CASE YOU FORGOT.
I'M ONLY SPEAKING FOR MYSELF.
THERE'S AT LEAST TWO PILLARS OF
PROTECTION IN HUMAN SUBJECTS.
THE INSTITUTIONAL REVIEW BOARD
AND INFORMED CONSENT.
IT'S OFFERED THROUGH A
PARTICIPANT THROUGH THE PROCESS
OF AN INFORMED CONSENT.
THE FIRST LAYER IS THE
INSTITUTIONAL REVIEW BOARD AND
THE SECOND IS INFORMED CONSENT.
AS CHRISTINE NOTED, YOU CAN'T DO
IT JUST BECAUSE YOU GOT CONCEPT
FROM THE INDIVIDUAL.
YOU HAVE TO SEND IT TO AN
INDEPENDENT GROUP TO EVALUATE
AND WE'LL TALK A LITTLE BIT
ABOUT WHY THAT'S THE CASE AND
WE'LL HAVE A WHOLE DAY ON
INFORMED CONSENT NEXT WEEK.
SO KEY POINTS IF YOU NAP FROM
THIS POINT ON TO THE END HERE'S
THE KEY POINTS.
IRBs ARE RESPONSIBLE FOR THE
REVIEW AND OVERSIGHT OF HUMAN
SUBJECT RESEARCH.
HERE IN THE UNITED STATES AND
AGAIN WHERE YOU ARE OUT THERE
YOU LIKELY HAVE SOME SORT OF
NATIONAL OR REGIONAL REGULATION.
IRBs ARE GUIDED IN THEIR REVIEW
BY FEDERAL REGULATIONS.
THE 45CFR CALLED THE COMMON
RULE.
IT'S COMMON TO MOST FEDERAL
AGENCIES.
ODDLY ONE EXCEPTION TO THAT RULE
IS THE FOOD AND DRUG
ADMINISTRATION WOULD HAVE THEIR
OWN CODE OF FEDERAL REGULATIONS
RELATED TO IRBs BUT THEY ARE
VERY SIMILAR IF NOT IDENTICAL AS
IT RELATES TO WHAT'S REQUIRED OF
IRBs.
IRBs ARE LOCAL AND THEY DEVELOP
THEIR OWN POLICY AND PRACTICE
AND THINK OF THE IRB AS YOUR
FRIEND NOT NEARLY AN
ADMINISTRATIVE BARRIER.
IF YOU HAVE A QUESTION ABOUT
WHETHER YOU'RE DOING RESEARCH,
WHETHER YOUR RESEARCH EXPOSES
INDIVIDUALS TO MORE THAN MINIMAL
RISK.
ASK SOMEBODY IN THE IRB.
THAT'S WHY THEY'RE THERE AND THE
EXPERTISE THEY HAVE.
A REMINDER FROM THE ARTICLE AND
THE BENCHMARKS DR. GRADY
REVIEWED, THE REASON WE DO THIS,
THE REASON WE HAVE THIS
INDEPENDENT REVIEW AND WE'LL
TALK WHETHER A LOCAL
INSTITUTIONAL REVIEW BOARD IS
REALLY INDEPENDENT.
THE IDEA IS THAT THE ROLE
THERE'S SOCIAL ACCOUNTABILITY
AND TRUST US WE'RE REVIEWING
THIS BEFORE IT GOES INTO A HUMAN
SUBJECT AND TO MINIMIZE THE
IMPACT OF A POTENTIAL
RESEARCHER'S INHERENT CONFLICT
OF INTEREST IN THEIR OWN WORK.
INTERESTINGLY I'M VERY
INTERESTED IN IRBs AS THE TOPIC
OF RESEARCH AND I HAVE QUESTIONS
IN TERMS OF THE WORK THAT I DO
BUT MANY YEARS AGO NOW IT WAS
NOTED UNQUESTIONABLY THERE'S THE
EXISTENCE OF IRB HAS TEMPERED
THE PROPENSITY OF RESEARCHERS TO
PURSUE INVESTIGATIONS WITHOUT
DISPASSIONATELY WEIGHING THE
RISK THEY'RE ASKING OTHER TO
ASSUME OR FULLY INFORMING
SUBJECTS.
THE MERE EXISTENCE SAY BIT OF A
DETERRENT FOR ROGUE
INVESTIGATORS TO EVEN ANTICIPATE
OR COME UP WITH A PROJECT THAT
MIGHT PUT HUMAN SUBJECTS AT A
HIGHER RISK AND IF THEY DID
PROPOSE SOMETHING LIKE THAT PART
OF THE IRB IS TO ASSUME THE RISK
AND BENEFITS ARE APPROPRIATELY
BALANCED.
SO HERE'S THE SORT OF ESSENTIAL
CONFLICT OF INTEREST.
YOU'RE AN INVESTIGATOR, YOU
THINK HOLY COW THIS MAY BE A
CURE FOR CONDITION A, B OR C.
BY DEFINITION OF BEING A HUMAN
YOU'LL HAVE A LOT OF FAITH IN
YOUR OWN THINKING ABOUT IT AND
JUSTIFICATION FOR DOING THE
RESEARCH.
SO THE IRB THERE IS TO HELP
TEMPER THAT CONFLICT OF
INTEREST.
THE EXCITE YOU SHOULD BE EXCITED
ABOUT YOUR RESEARCH BUT THE IRBs
ROLE IS TO PERHAPS TEMPER SOME
OF THAT EXCITE MANY.
-- EXCITEMENT.
THE IRB SAYS THIS LOOKS LIKE
EXCITING WORK.
LET'S MAKE SURE THE PLAN IS
SCIENTIFICALLY SOUND AND
APPROPRIATELY PROTECTS THE
SUBJECT.
ESSENTIALLY THAT'S WHAT THE JOB
OF THE IRB IS.
I'M GOING TO TALK A LITTLE BIT
ABOUT THE ROLE, THE SCOPE AND
RESPONSIBILITIES AND THE REVIEW
ITSELF AND WE WILL HAVE AGAIN 01
MINUTES FOR DISCUSSION.
AS A SAID, THEIR JOB, THE JOB OF
THIS BODY OF INDIVIDUALS IS THE
REVIEW AND OVERSIGHT OF HUMAN
SUBJECT RESEARCH.
HERE IN THE UNITED STATES AT
YOUR AVERAGE MEDICAL CENTER TRUE
AT THE NIH AS WELL, THE IRB,
THAT COMMITTEE THAT REVIEWS IS
ONE COMPONENT REFERRED TO AS THE
HUMAN PROTECTION PROGRAM OR SOME
VARIANT.
THERE'S AN INFRASTRUCTURE
REVIEWING WHAT YOU SUBMIT BEFORE
IT ACTUALLY GETS TO THE IRB TO
MAKE SURE THAT ALL THE
APPROPRIATE ADMINISTRATIVE
COMPONENTS ARE IN PLACE.
FOR EXAMPLE, WAS THERE
SCIENTIFIC REVIEW?
IF THERE WAS, PLEASE POST THAT
IN YOUR APPLICATION.
WAS IT REVIEWED BY THE BIO
SAFETY COMMITTEE?
DID YOU INCLUDE YOUR CONSENT
FORM?
ETCETERA, ETCETERA.
SOME THINGS NEED TO BE PART OF
THE PROPOSAL BEFORE IT GETS TO
THE IRB THE GROUP NEEDS TO MAKE
SURE.
THIS IS THE REGULATIONS -- OOPS,
IRBs NEED A MINIMUM OF FIVE
MEMBERS AND AMONG THOSE MEMBERS
ONE NEEDS TO BE UNAFFILIATED
WITH THE INSTITUTION AND ONE
NEEDS TO BE A NON SCIENTIST.
SOMETIMES IRBs HAS ONE PERSON
WHO MEETS BOTH.
BY DEFINITION THEY'RE OFTEN IN
THE MINORITY.
THEY'RE OFTEN LARGER THAN FIVE
A
AND CHALLENGING IN BEING A ROOM
OF SCIENTISTS BUT A KEY ROLE.
ACROSS THE GLOBE AS THE
DIFFERENT VERSIONS.
IN NEW ZEALAND MY FAVORITE IRB
MEMBERSHIP RULE IS THERE ALWAYS
HAS TO BE ONE MORE NON-SCIENTIST
THAN SCIENTIST.
IT MEANS THEY HAVE A BIG PLACE
AT THE TABLE AND I THINK THERE
SHOULD BE MORE REGULAR OLD
VOICES AT THE TABLE.
REGULATIONS DON'T REQUIRE THAT.
I SAY THEY SHOULD BE CLINICAL.
WE HAVE AN INTERESTING SETUP OF
ONE ENORMOUS GROUP OF PEOPLE WHO
SERVE ON THE IRBs.
THE IRB MEETS FOUR OR FIVE TIMES
A WEEK AND AT LEAST FIVE PEOPLE
ARE SLOTTED INTO THOSE MEETINGS
AND AS THE LOCAL AND IT CAN VAR
VARY IN THE REVIEW.
AS LONG AS THE VARIABILITY IS
NOT EXPOSING PEOPLE TO TOO MUCH
RISK OR APPROVING POORLY
REVIEWED RESEARCH, WE'RE HOPING
WE'RE SOMEWHERE IN THE MIDDLE
AND IRBs CONSIDER THINGS
DIFFERENTLY.
SOME OF THE CHALLENGES.
ONE I MENTIONED THERE'S A
CONFLICT OF INTEREST.
SO THINK ABOUT THE FOLLOWING.
LET'S SAY WE'RE AT BIG
UNIVERSITY A AND THE IRB IS MADE
UP OF FACULTY MEMBERS FROM BIG
UNIVERSITY A AND INCLUDES AT
LEAST ONE PERSON NOT FROM
UNIVERSITY A.
UNIVERSITY A RELIES IN PART FOR
THEIR BUDGETING ON THE GRANT
DOLLARS THAT COME INTO THAT
INSTITUTION.
SO THOSE PEOPLE AROUND THE TABLE
KNOW THAT THE RESEARCH THEY'RE
REVIEWING HAS LIKELY ALREADY
BEEN FUNDED IF THEY DON'T
APPROVE IT THE DOLLARS DON'T
COME TO THE INSTITUTION.
I THINK THAT'S A POTENTIAL
CONFLICT OF INTEREST AND IT
DOESN'T MEAN IT'S DOING A BAD
JOB BUT WE NEED TO ACKNOWLEDGE
THAT THAT MIGHT BE THE CASE AND
THAT INSTITUTIONS HAVE HIGH
STAKES WHEN THINKING ABOUT HOW
ALL THESE PIECES OF THEIR
INSTITUTION FIT TOGETHER.
YOU CAN ALSO HAVE AN INDIVIDUAL
CONFLICT OF INTEREST.
SO IF I'M SITTING ON THE IRB AND
A CO-INVESTIGATOR OF MINE ON
ANOTHER PROJECT SUBMITS AS
PRINCIPLE INVESTIGATOR A PROJECT
THEY WANT TO HAVE REVIEWED BY
THE IRB, I MIGHT HAVE TO SAY,
I'VE GOT TO STEP OUT BECAUSE I
HAVE A VERY CLEAR PROFESSIONAL
RELATIONSHIP WITH THIS PERSON.
I'M PRETTY SURE IT'S NOT GOING
TO INFLUENCE MY DECISION OR MY
DISCUSSION HERE BUT JUST TO BE
ON THE SAFE SIDE I'M GOING TO
STEP OUT.
OTHER CHALLENGES ARE BASICALLY
THE CULTURE OF IRBs.
SOME IRBs HAVE BEEN TOGETHER FOR
10 YEARS, 15 YEARS.
THEY MIGHT START TO HAVE GROUP
THINK AND IF THERE'S A STRONG
CHAIR THE GROUP MY START TO CEDE
TO THE CHAIR'S DECISION.
IT'S IMPORTANT TO THINK WITH THE
FACT THAT THERE ARE SOME
CHALLENGES IN HAVING AN
INDEPENDENT REVIEW.
BUT AS THE FIRST QUOTE SAID ONE
MIGHT ARGUE MERELY HAVING THE
GROUP IS AT LEAST HELPING ENSURE
MOST RESEARCH THAT'S CONDUCTED
PROTECTS THE HUMAN SUBJECTS
INVOLVED.
I MENTIONED IN RESPONSE TO THE
EARLIER QUESTIONS WHY DO YOU
NEED AN IRB AT YOUR INSTITUTION?
THE REGULATION SAYS IF YOU ARE
RECEIVING FEDERAL FUNDS MOST
PLACES DO THESE DAYS, YOU HAVE
TO REVIEW NOT ONLY THE RESEARCH
THAT'S FEDERALLY FUNDED BUT SO
IF I'M AT AN INSTITUTION, MY
PROJECT IS FUNDED BY THE GATES
FOUNDATION, NOT BY THE FEDERAL
GOVERNMENT BECAUSE I'M
AFFILIATED WITH AN ACADEMIC
MEDICAL CENTER RECEIVING FEDERAL
FUNDS I'M HELD TO THE SAME
STANDARD.
I HAVE TO SUBMIT MY PROTOCOL FOR
REVIEW.
THOUGH GATES IS ALSO GOING TO
REQUIRE THAT REVIEW.
MOST LARGE NONPROFITS SAY OF
COURSE YOU'LL GET A REVIEW AND
OVERSIGHT ONCE THE MONEY IS
ALLOCATED.
AS I MENTIONED THE ALSO REQUIRES
IRB REVIEW.
ANY PHARMACEUTICAL COMPANY
PRIVATE ACTOR WILL MAKE SURE
THEIR RESEARCH IS REVIEWED WITH
THE CAVEAT I MENTIONED EARLIER.
AS MENTIONED, THE WAY IN WHICH
THE FEDERAL GOVERNMENT SET UP
SOME REQUIREMENTS.
THE WAY THEY DO THAT IS THROUGH
A FEDERAL WIDE ASSURANCE.
EACH IRB, EACH LOCAL IRB HAS TO
LITERALLY ASSURE THE FEDERAL
GOVERNMENT THAT THEY ARE GOING
TO REVIEW ALL RESEARCH ACCORDING
TO CFR4546 ALSO POSTED IN CANVAS
IF YOU'D LIKE TO REVIEW IT AND
THEY'LL REVIEW IT REGARDLESS OF
FUNDING MECHANISM AND FOLLOW THE
PRINCIPLES OF BELMONT AND FOLLOW
INTERNATIONALLY RECOGNIZED
STANDARD.
FOR EXAMPLE IF IT'S A
NON-U.S. IRB WHO CAN ALSO
REGISTER FOR A FEDERAL WIDE
ASSURANCE WITH THE
U.S. GOVERNMENT THEY'LL FOLLOW
THE DECLARATION OF HELSINKI AND
A WELL REGARDED SET OF
REGULATIONS APPLIED MORE
INTERNATIONALLY.
I'M SURE I HAVE WILL SECTIONS
ASSIGNED FOR READING SO YOU'LL
SEE THE CIOMS AGAIN.
CHRISTINE MENTIONED A SUBSET OF
THE RESPONSIBILITIES IRBs HAVE.
MINIMIZING RISKS, MAKING SURE
THEY'RE REMEMBER WHEN COMPARED
TO BENEFIT, ETCETERA.
LITERALLY THIS IS ALL THE
FEDERAL REGULATIONS SAY ABOUT
THE REVIEW HENCE SOME LOCAL
VARIABILITY.
THE BASIC GUIDELINES ARE THERE
BUT IRBs INTERPRET THEM SLIGHTLY
DIFFERENTLY.
THERE'S A LOT OF ADDITIONAL
CRITERIA THAT THE IRB MAY ALSO
BE APPLYING.
LOCAL INSTITUTION POLICY.
THERE'S NIH GUIDELINES LIKE
WE'LL TALK ABOUT THIS LATER IN
THE CLASS.
INVESTIGATORS ARE HELD TO MAKE
SURE WOMEN AND MEMBERS OF
MINORITY POPULATIONS CHILDREN,
AND OLDER ADULTS ARE INCLUDED IN
RESEARCH AND SO THE IRB OUGHT TO
BE THINKING ABOUT THAT WHEN
REVIEWING THE RECRUITMENT PLAN
FOR THE PROJECT.
FDA, REGULATION, STATE LAWS,
NATIONAL COMMISSION
RECOMMENDATIONS.
SO, AGAIN THE REGULATIONS GIVE
THEM A VERY SPARSE OUTLINE AND
THE IRBs THEN FILL THAT IN WITH
ALL SORTS OF OTHER RESOURCES.
IRB'S REVIEW RESEARCH AND
ACCORDING TO THE FEDERAL
REGULATIONS, RESEARCH IS A
SYSTEMATIC INVESTIGATION
INCLUDING RESEARCH DEVELOPMENT
TESTING AND EVALUATION DESIGNED
TO CONTRIBUTE TO GENERALIZABLE
KNOWLEDGE.
A QUICK SIDE NOTE AS SOMEONE WHO
DOESN'T DO QUALITATIVE RESEARCH
IT DOESN'T MEAN WHEN I DO
RESEARCH THAT I KNOW IS NOT
GOING TO CONTRIBUTE TO
GENERALIZABLE KNOWLEDGE I'M
HOPING THAT THE KNOWLEDGE I
GENERATE WILL BE TRANSFERRABLE
TO OTHER SETTINGS SO OVER TIME
REMEMBERING THESE WERE FIRST
INTRODUCED BACK IN 1980, THEY
HAVE NOT CHANGED MUCH SINCE.
THE WORLD OF RESEARCH HAS
CHANGED QUITE A BIT IN THE
INTERIM.
THERE'S SOME READING BETWEEN THE
LINES OR APPLYING BEYOND THE
LETTER OF THE LAW AS IT WERE.
AND THERE'S IRBs IN CHARGE OF
TELLING YOU WHETHER OR NOT
YOU'RE RESEARCH FITS INTO ONE OF
THE CATEGORIES.
THERE'S SOME REASON THE IRB ONCE
YOU SUBMIT THE PROPOSAL SAY THIS
IS NOT HUMAN SUBJECT RESEARCH.
SO FOR EXAMPLE IF YOU WERE GOING
TO BE DOING LET'S SAY I'M GOING
TO BE DOING AN AMOUSE SURVEY OF
WHATEVER EVERYBODY ORDERED AT
THE -- ANONYMOUS ORDER OF WHAT
EVERYBODY ORDERED AT THE COFFEE
BAR TODAY.
THAT'S NOT REALLY HUMAN SUBJECT
RESEARCH.
I'M JUST ASKING SOME QUESTIONS
ABOUT HOW MAYBE I WANT TO RUN MY
COFFEE HOUSE.
IF I SUBMITTED A PROPOSAL TO THE
IRB THEY'D SAY, HOLLY, YOU KNOW
THAT'S NOT HUMAN SUBJECT
RESEARCH.
ANOTHER CATEGORY THAT THERE ARE
EIGHT CRITERIA FOR ARE EXEMPT
FROM IRB REVIEW THOUGH THE
EXEMPT IS A LITTLE TRICKY.
SO IF YOUR PROJECT MEETS ONE OF
THE EIGHT CRITERIA AND THERE'S
NO MORE THAN MINIMAL RISK,
YOU'RE RESEARCH IS EXEMPT FROM
IRB REVIEW BUT YOU STILL HAVE TO
SUBMIT A PROPOSAL FOR WHAT
YOU'RE PLANNING TO DO SO THE IRB
CAN DETERMINE THAT IT'S EXEMPT.
SO WE AS INVESTIGATORS CAN'T
MAKE THAT DECISION.
WE HAVE TO LET THE IRB MAKE THAT
DECISION.
TWO OTHER CATEGORIES, EXPEDITED
AND FULL COMMITTEE REVIEW.
SO EXPEDITED RESEARCH IS
RESEARCH THAT'S NOT EXEMPT WHEN
THERE IS NO MORE THAN MINIMAL
RISK AND IT DOESN'T HAVE TO GO
TO THE FULL COMMITTEE.
IT CAN BE REVIEWED BY A
CHAIRPERSON OR AN EXPERIENCED
REVIEWER.
YOU MIGHT THINK EXPEDITED MEANS
QUICKER.
DOESN'T ALWAYS MEAN THAT.
IT DOES MEAN THAT THE PROCESS IS
BRIEFER PERHAPS BUT IT DOESN'T
ALWAYS MEAN FASTER.
THE FINAL CATEGORY IS FULL
COMMITTEE REVIEW.
SO IT IS GOING TO BE MORE THAN
MINIMAL RISK.
ANY RESEARCH THAT EXPOSES A
HUMAN SUBJECT TO MORE THAN
MINIMAL RISK HAS TO BE REVIEWED
BY A FULL COMMITTEE.
THERE'S EXCEPTIONS TO THIS.
I'LL GIVE A QUICK EXAMPLE.
I DID RESEARCH WITH A FELLOW
LAST YEAR WHERE WE DID AN
ANONYMOUS SURVEY OF PARTICIPANTS
ABOUT THEIR EXPERIENCE WITH
COVID VACCINATION.
WOULD BE EXEMPT IF OUR SUBJECTS
WERE ADULTS BUT THEY WERE UNDER
18 THEREFORE CHIRP IN THE EYES
OF THE REGULATION.
NO MORE THAN MINIMAL RISK BUT WE
HAD TO SUBMIT THAT FOR EXPEDITED
REVIEW.
THERE'S LITTLE EXCEPTION AND IF
YOU HAVE A QUESTION, ASK YOUR
REVIEW COMMITTEE ALWAYS IN MY
OPINION BETTER TO UNDERSTAND
WHAT THE EXPECTATION IS SO
YOU'RE NOT DISAPPOINTED WHEN
THEY SAY, HOLLY YOU SAID THIS IS
EXEMPT.
IT'S NOT.
YOU HAVE TO SUBMIT A FULL
PROPOSAL BECAUSE IT'S EXPEDITED,
ETCETERA.
A LITTLE ABOUT THE REVIEW
PROCESS.
THERE'S THE INITIAL
ADMINISTRATIVE REVIEW OF THE
RESEARCH PLAN, CONSENT
DOCUMENTS.
IF YOU'RE GOING TO ADVERTISE THE
NEEDS TO REVIEW IT.
I HAVE THIS DIAGRAM BECAUSE I'M
GOING TO SHOW YOU IT AGAIN.
IF YOU THINK ABOUT THAT HUMAN
RESEARCH PROTECTION PROGRAM
THERE'S AN OFFICE IN CHARGE OF
ADMINISTRATIVE REVIEW,
COORDINATING ANCILLARY REVIEWS
THE RESEARCH IS ALSO GOING
THROUGH AND THEN THE GREEN BOX
IS TO REPRESENT THE IRB.
THAT'S THE HUMAN SUBJECTS
REVIEW.
WHEN THE IRB GETS TOGETHER THERE
SHOULD BE SOME DELIBERATION
ABOUT THE PROJECT.
THERE'S GOING TO BE A
PRESENTATION VIA PRIMARY OR
SECONDARY REVIEWER.
HOPEFULLY THERE'S DISCUSSION
ABOUT KEY ETHICAL CONCERNS AND
THEN THERE'S A DECISION.
APPROVAL, APPROVAL WITH SOME
SORT OF STIPULATION OR
CONDITION.
IF THERE'S A COUPLE BIG THINGS
PROBLEMATIC IT MIGHT BE DEFERRED
OR DISAPPROVED.
AND DISAPPROVAL IS VERY RARE IN
MY EXPERIENCE OF VIEWING MANY
MANY PROPOSALS.
STIPULATION IS THE MOST COMMON
THING AN IRB IS GOING TO DO.
THEY MIGHT APPROVE IT AS IS BUT
IN MY EXPERIENCE THAT'S ALSO
RELATIVELY RARE.
SO AFTER THAT INITIAL REVIEW,
THE IRB IS ALSO RESPONSIBLE FOR
CONTINUING REVIEW OF PROPOSALS
THAT WENT TO THE FULL COMMITTEE
FOR REVIEW.
SO NOT THE EXPEDITED, NOT THE
EXEMPT BUT ALL THAT RESEARCH
THAT WAS REVIEWED INITIALLY IF
IT'S CONTINUING, IT'S NOT JUST A
ONE AND DONE AS IT WERE, YOU'RE
REQUIRED TO GIVE AT LEAST AN
ANNUAL UPDATE TO THE IRB.
THE IRB HAS THE WHEREWITHAL TO
ASK YOU TO COME BACK MORE
FREQUENTLY.
THEY CAN SAY, YOU KNOW WHAT,
THIS IS FIRST IN HUMAN.
REALLY INTERESTING NOVEL
TREATMENT.
WE WANT TO SEE THIS AFTER SIX
MONTHS BECAUSE WE JUST WANT TO
SEE HOW IT'S GOING AND HOW THE
RESEARCH IS ACCRUING PATIENTS,
ETCETERA.
YOU ALSO NEED TO GO BACK TO THE
IRB IF YOU HAVE AN AMENDMENT.
MAYBE YOU WANT TO ADD A NEW
ADVERTISEMENT OR YOU WANT TO
EXPAND YOUR POPULATION BECAUSE
IT'S PRETTY CLEAR YOU'RE NOT
GOING TO BE ABLE TO MEET THE
NUMBER THAT YOU HAD BECAUSE A
LOT OF PEOPLE ARE DROPPING OUT.
ANYTHING LIKE THAT EVEN IF
SOMEONE ON YOUR TEAM IS A
LEADING INSTITUTION YOU HAVE TO
AMEND YOUR PROTOCOL AND
IMPORTANTLY YOU NEED TO REPORT
TO THE IRB ANY ADVERSE EVENTS
THAT OCCURRED.
THOSE ARE -- UNLESS THEY ARE
SEVERE ADVERSE EVENTS WHERE YOU
HAVE TO REPORT THEM RIGHT AWAY
YOU REPORT THOSE TO THE IRB ON
AN ANNUAL BASIS.
I'M GOING TO BRIEFLY TALK ABOUT
THE SINGLE IRB OF RECORD POLICY
HERE IN THE UNITED STATES.
OVER TEENS IN THE 2000s THERE
WAS FEEDBACK REQUESTED, NEW
DRAFTS, ETCETERA, THAT RESULTED
IN TWO POLICIES ABOUT IS THE USE
OF AN IRB FOR SINGLE SITE
RESEARCH.
ALL RESEARCH FUND THE NIH IF
IT'S MULTISITE IT HAS TO BE
REVIEWED BY A SINGLE IRB AND A
COUPLE YEARS LATER WAS ADOPTED
INTO THE REVISION OF THE COMMON
RULE.
SO NOW ANY RESEARCH FUND
RESEARCH AND HUMAN SERVICES
INCLUDING THE NIH HAS TO DO A
SINGLE IRB WHEN DOING MULTI-SITE
RESEARCH.
I'M BRINGING BACK MY DIAGRAM.
IF YOU WERE DOING A RESEARCH
PROJECT WHERE YOU HAD MULTIPLE
CENTERS AND IMAGINE AN ONCOLOGY
TRIAL WITH 39 DIFFERENT SITES.
BEFORE THIS POLICY YOU HAD THE
OPTION OF USING A SINGLE IRB BUT
IT WAS NOT COMMON.
EVERY SITE PLANNING TO APPROVE
TO APPROVE PATIENTS AND AND FIVE
IRBs WOULD REVIEW THE SITE AND
IF THERE'S A COORDINATING CENTER
THERE WOULD ALSO BE A REVIEW
THERE AND GET A TOTAL OF SIX IRB
REVIEWS.
NOT SURPRISINGLY, THIS WAS
FRUSTRATING TO INVESTIGATORS,
LOTS OF EMPIRICAL EVIDENCE THAT
MULTIPLE REVIEWS MEANT LOTS OF
TIME A QUICK IRB CAN GET IT DONE
IN JANUARY AND THEN ONE IN MAY
AND JULY AND AUGUST.
IF YOU WANT TO FACILITATE THE
CONDUCT OF HIGH QUALITY RESEARCH
THAT WAS A GRAY AREA.
THIS IS WHAT HAPPENS AFTER THE
POLICY.
I MOVED THE LITTLE GREEN BOX TO
THE COORDINATING CENTER.
THE COORDINATING CENTER MIGHT BE
ONE OF THE ACADEMIC MEDICAL
CENTERS.
ONE CAN SELF-DESIGNATE AS THE
SINGLE IRB OF REPORT OR THE
GROUP COULD DECIDE TO GO TO A
COMMERCIAL IRB OF WHICH THERE
ARE A COUPLE IN THE UNITED
STATES THESE DAYS.
THERE'S ONE SINGLE IRB REVIEW
AND IT GOES OUT TO THE OTHER
FIVE SITES AND THAT'S THE REVIEW
OF RECORD.
BUT IT DOESN'T MEAN THEY'RE NOT
RESPONSIBLE FOR THE ANCILLARY
REVIEWS.
DID IT GO THROUGH THE BIO SAFETY
COMMITTEE?
DID IT GO THROUGH THE GROUP
REVIEWING THE PHARMACEUTICAL AND
TREATMENT GROUP?
WHAT IS THE RELATIONSHIP WITH
GRANTS AND CONTRACTS.
WHILE THE GOAL WAS TO FACILITATE
THE REVIEW AND APPROVAL, THERE'S
STILL A LOT GOING ON AT THAT
LOCAL SITE THAT NEEDS TO HAPPEN
AND THE POLICY HAS BEEN IN PLACE
NOW JUST A COUPLE YEARS.
THERE'S ONGOING EMPIRICAL
RESEARCH AND PROBABLY WON'T BE
CLEAR FOR A NUMBER OF YEARS
WHETHER THE POLICY HAS HAD THE
EFFECT OF STREAMLINING THE
REVIEW AND APPROVAL OF RESEARCH.
THE GOAL WAS CLEARLY TO EXPEDITE
THAT REVIEW BECAUSE THE MULTIPLE
REVIEWS WERE SLOWING THINGS
DOWN.
TO BE DETERMINED.
A QUICK SIDE NOTE.
I'LL SAY I'M A BIG PROPONENT OF
WHAT I'LL CALL EMPIRICALLY
INFORMED POLICY.
PRIOR TO THE SINGLE IRB RECORD
POLICY THERE WAS NO EMPIRICAL
EVIDENCE THIS SYSTEM WOULD BE
MORE EFFICIENT THAN THE
TRADITIONAL SYSTEM.
IF YOU HAD ASKED ME I MIGHT HAVE
FUNDED SOME SORT OF
DEMONSTRATION PROJECTS TO
DETERMINE HOW THIS WAS ALL GOING
TO WORK OUT BEFORE IT BECAME A
NATIONAL POLICY.
BECAUSE IRBs ARE LOCAL, YOU CAN
IMAGINE THAT THERE'S A LOT OF
HETEROGENEITY BUT I'M NOT THE
BENEVOLENT DICTATOR SO THEY
DIDN'T ASK ME.
IRBs HAVE REGULATIONS TO FOLLOW
AND THEY'RE LOCAL AND IF YOU
EVER HAVE A QUESTION THEY'RE THE
PEOPLE TO ASK AND NOW WE HAVE 10
MINUTES FOR QUESTIONS AND I LOVE
TO ANSWER QUESTIONS.
>> I WANTED TO ASK ABOUT THIS
LOCAL AND AUTONOMOUS COMPONENT.
SO I WAS HOPING YOU COULD TELL
US A LITTLE BIT MORE ABOUT WHY
THEY'RE SET UP THIS WAY AND
WHETHER OR NOT YOU THINK IT'S A
GOOD IDEA FOR THEM TO BE SET UP
THIS WAY GIVEN THERE'S OTHERWISE
A LOT OF FEDERAL REGULATION OR
INTERNATIONAL AGREEMENT HOW THEY
OUGHT TO BE SET UP.
>> GREAT QUESTION.
INTERESTINGLY ENOUGH IF YOU LOOK
BACK AT THE ORIGINAL POLICY THAT
WAS PLANNED TO BE IMPLEMENTED --
SO ANOTHER QUICK REVIEW AND TIME
LINE.
WE HAD TUSKEGEE SYPHILIS STUDY
AND THE NATIONAL COMMISSION IN
1974, BELMONT REPORT IN 1978.
AFTER 1978 THE BELMONT REPORT
WAS BASICALLY TRANSFORMED INTO A
SET OF REGULATIONS WE HAVE
TODAY.
ONE OF THE THINGS THAT WERE IN
THE FIRST SET OF REGULATIONS --
THIS WAS IN THE LATE '70s SAID
ISHAK DEMOCRATIC MEDICAL
INSTITUTIONS HAVE A CHOICE.
THEY CAN EITHER SET UP THEIR OWN
LIKAL IRB ACCORDING TO THE
FEDERAL REGULATIONS AND LET US
KNOW, THE FEDERAL GOVERNMENT
GOVERNMENT THAT'S WHAT THEY'RE
DOING OR SEND ALL THEIR RESEARCH
TO A FEDERAL GOVERNMENT FOR
REVIEW.
IT MIGHT HAVE BEEN FEASIBLE IN
1979.
CLEARLY NOT FEASIBLE TO MANY AND
IT MEANT THAT IN ORDER FOR THE
RESEARCH TO BE REVIEWED
SYSTEMATICALLY IT HAD TO BE SENT
DOWN TO THE LOCAL INSTITUTION.
IT COULD HAVE BEEN AT THAT POINT
THEY SAID, INTERESTING, YOU
KNOW, THERE'S CONFLICTS OF
INTEREST THAT MAY BE EMBEDDED IN
AN INSTITUTIONAL REVIEW BOARD
THAT'S LOCAL.
MAYBE WE CAN HAVE REGIONAL IRBs
OR ONE THEY ALL USE THAT ADHERES
TO THE FEDERAL GOVERNMENT'S
REGULATIONS BUT WE END YOU HAD
UP WHERE WE ARE TODAY WHERE EACH
INSTITUTION IS LOCAL AND ADOPTS
THEIR OWN APPROACH.
THEY HAVE MUCH MORE IN COMMON
THAN THEY DON'T HAVE IN COMMON.
AS I MENTIONED, THERE'S
EMPIRICAL EVIDENCE IN THE
LITERATURE THAT OUR GUEST
LECTURER IN A COUPLE DAYS ON THE
INCLUSION OF CHILDREN IN
RESEARCH WHILE SHE WAS A FELLOW
HERE OR ON FACULTY SHE SENT OUT
A SURVEY TO IRB CHAIRS AND SAID
HERE'S RAY LIST OF A BUNCH OF
PROCEDURES THAT MIGHT BE
PROPOSED IN A PROJECT INCLUDING
CHILDREN.
BLOOD DRAW, FISCAL, LUMBAR
PUNCTURE, SKIN BIOPSY,
GASTROINTESTINAL BIOPSY.
YOU, IRB CHAIR TELL US HOW YOUR
IRB WOULD DESIGNATE ANY OF THESE
AS MINIMAL RISK OR MORE THAN
MINIMAL RISK.
YOU CAN GUESS WHERE THE OUTCOME
IS.
THERE WAS VARIABILITY.
SO WHILE EVERYBODY SAID A BLOOD
DRAW WAS NO MORE THAN MINIMAL
RISK SOME SAID A LUMBAR PUNCTURE
WAS NO MORE THAN MINIMAL RISK.
THE HETEROGENEITY MATTERS IF WE,
WHO ARE INTERESTED IN WHO IS
BEING EXPOSED TO RESEARCH, THAT
IT AIRS ON THE SIDE OF EXPOSING
HUMAN SUBJECTS TO MORE RISK THAN
THEY WOULD BE EXPOSED TO
OTHERWISE.
AND AS FAR AS I KNOW THERE'S NO
EVIDENCE CLEAR EVIDENCE THAT
THAT HETEROGENEITY LEADS TO
UNACCEPTABLE HARMS AND ONE THING
THE SINGLE IRB REVIEW MIGHT
REMEDY IS THAT IF THE SINGLE IRB
SAYS OH, GOSH, LUMBAR PUNCTURES
ARE MORE THAN MINIMAL RISK AND
THERE'S GENERAL AGREEMENT THE
CENTERS THEY'RE BEHOLDEN TOO
HAVE TO FOLLOW THE SAME
GUIDELINE.
SO SOME WOULD ARGUE IRBs ARE
CONSERVATIVE AND TOO CAREFUL AND
AN ADMINISTRATIVE BARRIER AND
IMAGINE THE ADVANCES WE WOULD
MAKE IF THEY WEREN'T SO STRICT
ABOUT PROTECTING HUMAN SUBJECTS
FROM RISK.
THERE'S VALUE IN KNOWLEDGE AND
CURING DISEASE AND MAKING
SCIENTIFIC ADVANCES BUT YOU HAVE
THIS PRESSURE TO MINIMIZE THE
POTENTIAL RISKS WHICH IS A GOOD
THING.
AND BECAUSE WE TALKED ABOUT THE
FACT THAT ALL THESE PLACE LOCAL,
YOU CAN IMAGINE WHY A LOCAL
INSTITUTION MIGHT BE MORE
CONSERVATIVE IN ERRING ON THE
SIDE OF NOT PUSHING THE
ENVELOPE.
THERE'S A HISTORY IN THE REVIEW
OF HUMAN SUBJECT RESEARCH WHERE
A NUMBER OF INSTITUTIONS WERE
CLOSED DOWN FOR A VARIETY OF
REASONS ACADEMIC MEDICAL
CENTERS, DUKE, JOHNS HOPKINS,
ETCETERA.
THAT'S A RISK THEY REALLY WANT
TO AVOID.
THERE'S A LOT OF DIFFERENT
PIECES OF THE PUZZLE THAT NEED
TO BE PUT TOGETHER.
IT MAY BE TRUE IF WE EXPOSED
HUMANS TO MORE RISK WE'D MAKE
FASTER PROGRESS.
SOME OF YOU LEARNED IN THE NIH
ORIENTATION THE VAST MAJORITY OF
RESEARCH OR ONE BIG CHUNK OF
RESEARCH THAT HAPPENS HERE AT
THE CLINICAL CENTER IS PHASE 1
RESEARCH.
IT'S THE OPPOSITE IN THE WORLD
THE AT ACADEMIC MEDICAL CENTER
AND DO LESS PHASE 1 RESEARCH AND
MORE PHASE 2 AND PHASE 3
RESEARCH.
SO THERE ARE REASONS WHY
CALCULUS IS COMPLICATED AN
PLACES LIKE THE CLINICAL CENTER
CAN SORT OF AFFORD PUSHING THE
ENVELOPE IN A WAY AN ACADEMIC
MEDICAL INSTITUTE AND CENTER MAY
NOT BE WILLING TO.
THAT'S THE BALANCE WE HAVE IN
MAKING PROGRESS.
CAROLINE.
>> I'M WONDERING HOW YOU DEFINE
IRB COMMITTEES BEING
CONSERVATIVE BECAUSE THEY SEEM
TO APPROVE THE VAST MAJORITY OF
APPLICATIONS.
THE VAST MAJORITY OF RESEARCH AN
IRB REVIEWS IS EVENTUALLY
APPRESSED.
THERE'S A CONDITION THE
INVESTIGATOR HAS TO FIX.
WHAT I MEAN BY CONSERVATIVE IS
THAT IF THEY REVIEW A PROTOCOL
WHERE THERE'S CONCERN ABOUT
RISKS, THEY MAY FOCUS ON HOW THE
INVESTIGATOR OUGHT TO MINIMIZE
THOSE RISKS AND PUSH THE
INVESTIGATOR TO DROP PARTICULAR
ASPECTS OF THE PROTOCOL TO MAKE
SURE THEY ARE PROTECTING
SUBJECTS FROM THE MOST EXTREME
RISK THEY MAY BE EXPOSED TO.
AND INVESTIGATORS KNOW THIS AND
KNOW IRBs WILL NOT BE OPEN TO
APPROVING RESEARCH THAT MIGHT
PUSH THE ENVELOPE IN A
PARTICULAR WAY.
SO IT KIND OF FEEDS ON ITSELF.
WHAT I MEAN BY CONSERVATIVE IS
BEING VERY CAREFUL IN MAKING
SURE THE POTENTIAL DIRECT
BENEFITS TO THE SUBJECTS, THE
BENEFIT TO FUTURE PATIENTS.
THE BENEFITS OF THE LARGER
POPULATION IS IN BALANCE WITH
THE POTENTIAL RISK THEY'RE
EXPOSING THE SUBJECTS TO.
GREAT, IT'S 11:30.
THANK YOU FOR ATTENDING IN
PERSON FOR THOSE WHO MADE THE
TREK.
WE'LL NOT MEET HERE NEXT WEEK.
WE'LL MEET IN BUILDING 31.
I'M GOING SHARE DIRECTIONS WITH
OUR FELLOWS.
I'M HAPPY TO SHARE THEM WITH YOU
AS WELL.
COME UP AND PUT YOUR E-MAIL
ADDRESS OR SEND ME AN E-MAIL AND
I'LL SEND THEM BACK TO YOU.
MY E-MAIL IS STRAIGHTFORWARD,
HOLLY.TAYLOR2@NIH.gov.
YOU CAN REACH OUT TO THE
BIOETHICS INQUIRY AND IT WILL GO
TO CONNOR AND WE'LL MAKE SURE
YOU GET DIRECTIONS.
THANK YOU.