>> GOOD MORNING.

I'D LIKE TO THANK EVERYONE

FOR COMING TO TODAY'S

LECTURE, INNOVATIVE

APPROACHES TO CLINICAL

TRIALS.

THE MEDICINE, THE MINDS THE

GAP SERIES EXPLORES A WIDE

RANGE OF ISSUES AT THE

INTERSECTION SF SEARCH

RESEARCH, EVIDENCE AND

CLINICAL PRACTICE,

ESPECIALLY IN AREAS WHERE

CONVENTIONAL WISDOM MAY LEAD

US ASTRAY.

FROM MEDICAL RESEARCH AND

POLICY TO OFF-LABEL DRUG USE

TO THE EFFECTIVENESS OF

CONTINUING MEDICAL EDUCATION,

THE SEMINAR SERIES AIMS TO

ENGAGE THE NIH COMMUNITY IN

THOUGHT-PROVOCATING

DISCUSSIONS TO CRITICALLY

THINK ABOUT OUR ROLE IN

TODAY'S RESEARCH

ENVIRONMENT.

TODAY'S LECTURER DR. ROBERT

CAIL YEF WILL CHALLENGE OUR

THINKING AROUND CLINICICAL

TRIAL.

HE IS DIRECTOR OF THE DUKE

TRANSLATIONAL MEDICINE

INSTITUTE.

AND PROFESSOR OF MEDICINE IN

THE DIVISION OF CARDIOLOGY

AT THE DUKE UNIVERSITY

MEDICAL CENTER.

HE IS ALSO THE EDITOR AND

CHIEF OF AMERICAN HEART

JOURNALISM AND IS THE --

JOURNAL AND THE AUTHOR OF

MORE THAN 1,000 PEER REVIEW

JOURNALISMS.

-- JOURNALS FOR HEALTHCARE

PROFESSIONALS INVOLVED IN

THE DIAGNOSIS AND MANAGEMENT

OF CARDIOVASCULAR DISEASE.

HE CURRENTLY SERVES AS

CO-CHAIR OF THE CLINICAL

TRIALS TRANSFORMATIONAL

INITIATIVE FOCUSED ON

IMPROVING THE CLINICAL TRIAL

SYSTEM AND IS CHAIR OF AN

ORGANIZATION OF ACADEMIC

HEALTH AND SCIENCE SYSTEM

LEADERS FOCUSED ON THE

IMPROVEMENT OF THE CLINICAL

RESEARCH ENTERPRISE, A

MEMBER OF THE NATIONAL

ADVISORY COUNCIL ON AGING,

HE ALSO SERVES ON THE

SECRETARY'S ADVISORY COUNCIL

ON HUMAN RESEARCH FOR THE

U.S. DEPARTMENT OF HEALTH

AND HUMAN SERVICES.

DR. CAILIFF RECEIVED HIS

UNDERGRADUATE DEGREE FROM

DUKE UNIVERSITY AND HIS MD

FROM DUKE UNIVERSITY MEDICAL

SCHOOL.

PLEASE JOIN ME IN WELCOMING

DR. ROBERT CAILIFF.

>> THANKS.

IT'S GREAT TO BE HERE AND A

LITTLE INTIMIDATING, THOUGH.

I WAS THINKING BACK.

I'VE NEVER BEEN SCHEDULED TO

GIVE A LECTURE WHERE THE

SESSION LASTED TWO HOURS.

SO MY INSTRUCTIONS WERE ONE

HOUR OF LECTURE BUT I WAS

TOLD IT WAS LIKELY THAT I

WOULD BE INTERRUPTED AND I

WOULD WELCOME YOU TO

INTERRUPT.

MANY OF YOU WHO I RECOGNIZE,

HAVE SEEN PARTS OF THIS

LECTURE BEFORE, AND AS USUAL,

I AM GOING TO TAKE A LOT OF

LICENSE TO PROVIDE YOU WITH

OPINIONS BECAUSE I THINK FOR

BETTER OR WORSE, PEOPLE SEEM

TO LIKE IT WHEN YOU GIVE

OPINIONS OFTEN TO TELL ME

THAT I AM WRONG.

AND BECAUSE I REALLY HOPE TO

CONVINCE YOU, IF NOT ALREADY

CONVINCED THAT, INCREM

CHANGES IF OUR CLINICAL

TRIAL SYSTEM WILL NOT BE

SUFFICIENT, THAT WE HAVE TO

REALLY PREPARE OURSELVES FOR

A MAJOR TRANSFORMATIONAL

CHANGE AND MUCH OF THE

LECTURE IS DEVOTED TO

DEFINING THE PROBLEM.

BUT I THINK YOU'LL SEE THAT

IN THE CONTEXT OF DEFINING

THE PROBLEM THERE IS A WAY

OUT OF THE BOX, WHICH IS

ACTUALLY TECHNOLOGICALLY A

NON-PROBLEM NOW.

REALLY TURNS OUT TO BE A

EMOTIONAL AND CULTURAL SET

OF ISSUES THAT WE'RE GOING

TO HAVE TO GET OVER IF WE

WANT TO MAKE THE NEXT SET OF

ADVANCES IN HEALTH AND

HEALTHCARE.

SO LET'S SEE.

LET'S TRY THAT ONE.

THERE WE GO.

OKAY, SO ALWAYS NEED TO

START WITH THE CONFLICTS OF

INTEREST.

I'VE HAD A LOT OF FUN WITH

THIS IN MY RECENT JOBS IN

THINKING ABOUT CONFLICT OF

INTEREST.

SO AT THE TOP I HAD MY USUAL

CONFLICTS THAT PEOPLE LOOK

FOR AND WE'VE DEVELOPED A

PUBLIC WEBSITE AND WE KEEP

IT UP TO DATE ONCE A

QUARTER.

BUT FOR THIS LECTURE, I ALSO

HAVE TO NOTE I ACTUALLY

THINK MY MAIN CONFLICT IS

NOT MY INDUSTRY I REPEAT

ACTIONS.

IT'S THE FACT THAT I DO THIS

FIRE LIVING SO I HAVE A BIT

OF A VESTED INTEREST IN HOW

THIS TURNS OUT AND WITH THIS

AUDIENCE, GRANTS AND

CONTRACTS WITH THE NIH,

THERE IS A VERY DIRECT

CONFLICT AND PISSING

SOMEBODY OFF OR MAKING

SOMEBODY FEEL GOOD ABOUT

WHAT I AM DOING.

SO FIRST OF ALL, THE WORD

INNOVATION HAS BECOME SUCH A

COMMONLY USED WORD.

I REMEMBER IN JUNIOR HIGH

SCHOOL I HAD AN ENGLISH

TEACHER WHO WOULD NOT ALLOW

ME TO USE THE WORD VERY

BECAUSE EVERYBODY USED THE

WORD VER.

THE WORD INNOVATE AT THE NIH

NOW -- I DON'T REALLY FOE.

IT'S USED TO IMPRESS PEOPLE

WITH SOMETHING BUT I'M NOT

SURE WHAT IT IS.

SO I WEPT BACK AND -- WENT

BACK AND LOOKED AND

INVENTION IS THE CREATION OF

A NEW IDEA.

INNOVATION, ACCORDING TO THE

WAY PEOPLE THINK, IS TAKING

A NEW CONCEPT AND EITHER

COMMERCIAL SUCCESS AND

WIDESPREAD USE AND

IMPLEMENTING BY PUTTING

THINGSING TO.

I ALSO FOR THE PURPOSES OF

THIS LECTURE, AM GOING TO

FOCUS ON INTERVENTIONAL

CLINICAL TRIALS THAT ARE

RANDOMIZED.

BUT I THINK IT'S IMPORTANT

TO NOTE SOMETHING THAT I

LAERPDS IN MY WORK AT THE

NATIONAL LIBRARY OF MEDICINE

THAT THE OFFICIAL NIH

DEFINITION OF A CLINICAL

TRIAL IS NOT NECESSARILY

INVOLVING RANDOMIZATION BUT

REALLY IS A BROAD DEFINITION

OF HUMAN STUDIES THAT I'VE

GIVEN HERE.

BUT THE MAIN PURPOSE OF MY

LECTURE IS TO TRY TO

CONVINCE YOU THAT, AS A

FRIEND SAID DAY BEFORE

YESTERDAY IN A CITY MEETING,

THE OM DIFFERENCE BETWEEN

CLINICAL PRACTICE AND A

RANDOMIZED TRIAL SHOULD BE

THE TOSS OF A COIN.

AND I REALLY THINK THAT'S

THE WAY WE NEED TO CHANGE

THE FUNDAMENTAL WAY THAT

WE'RE THINKING ABOUT

MEDICINE AND CLINICAL

PRACTICE.

SO I AM GOING TO TALK A LOT

ABOUT THE PROBLEMS.

THAT'S THE EASY PART,

BECAUSE IF YOU DISAGREE WITH

ME ABOUT THE PROBLEMS, I AM

PREPARED WITH A LOT OF

BACKUP MATERIAL.

I AM GOING TO TALK ABOUT

WHAT I SEE AS THE

OPPORTUNITY AND HERE THERE

COULD BE A LOT OF

DISAGREEMENT ABOUT THE

FEASIBILITY OF THE

OPPORTUNITY AND THEN TALK

ABOUT HOW TO TAKE THE

OPPORTUNITIES AND SOLVE THE

PROBLEMS.

I THINK IT'S INCREASINGLY

IMPORTANT FOR ME WHEN I LIVE

A -- GIVE A LECTURE LIKE

THIS TO POINT OUT THE

PROBLEMS I AM GOING TO BE

TALKING ABOUT ARE A GOOD

THING.

WE HAVE THESE PROBLEMS

BECAUSE WE'VE MADE SO MANY

ADVANCES THAT IN MY VIEW,

WE'VE EXHAUSTED THE OLD

METHODS AND THE OLD WAY OF

THINKING, AND IN ORDER TO

TAKE THE NEXT LEAP, WE'RE

GOING TO HAVE TO CHANGE THE

FUNDAMENTAL PARADIGM FOR THE

WAY THINGS ARE DONE.

THIS IS A GOOD PROBLEM TO

HAVE.

I DON'T KNOW WHY, BUT I WAS

BORN WITH A PERSONALITY TO

-- I TRY TO IDENTIFY

PROBLEMS AND SOLVE THEM.

SO I AM ALWAYS TALKING ABOUT

PROBLEMS AS OPPOSED TO GOOD

THINGS AND SOMETIMES PEOPLE

GET DEPRESSED WHEN I GIVE

LECTURES.

BUT YOU SHOULDN'T BE

DEPRESSED BY THIS LECTURE

BECAUSE I THINK IT'S THE END

RESULT OF SOME VERY POSITIVE

THINGS.

SO THIS IS THE BOTTOMLINE IF

YOU GO TO ASLEEP DURING THE

NEXT -- SLEEP DURING THE

NEXT HOUR AND 55 MINUTES

FROM MY PERSPECTIVE.

REALLY THE PALM PROBLEM IS

THAT -- FUNDAMENTAL PROBLEM

IS THAT OUR KNOWLEDGE HAS

EXCEEDED THE ABILITY TO

PROVIDE SUPPORT FOR DECISION

MAKING, THAT IS, REGARDLESS

OF WHAT REALM OF SCIENCE YOU

ARE TALKING ABOUT, THE

FUNDAMENTAL BASIS OF

KNOWLEDGE IS MOVING VERY

RAPIDLY AND WHEN WE DO

CLINICAL TRIALS, WE'RE

TALKING ABOUT A PROLONGED

PERIOD OF DESIGN, OFTEN

BIDDING FOR CONTRACTS, THE

STARTUP PHASE AND A VERY

LONG TIME TO GET THINGS DONE

WITH LIMITED POPULATIONS OF

PEOPLE.

AND WHETHER YOU ARE TALKING

ABOUT SYSTEMS BIOLOGY FOR

EARLY PHASE, CLINICAL TRIALS

OR YOU ARE TALKING ABOUT

ASSESSING RISK BENEFIT OF

THERAPEUTICS, ARE YOU

TALKING CLINICAL EFFECTIVENESS

AND THE APPLICATION OF WHAT

WE KNOW IN THE COMMUNITY, WE

CAN'T AFFORD TO WAIT FOR THE

PERIOD OF TIME IT'S

CURRENTLY TAKING TO DO

CLINICAL TRIALS AND WE CAN'T

RELEGATE THE QUESTIONS THAT

WE ASK.

SUCH A SMALL SET OF

QUESTIONS WHEN THERE ARE SO

MANY IMPORTANT AND

UNANSWERED QUESTIONS.

AND I THINK THERE IS A

FUNDAMENTAL THREE-COMPARTMENT

MODEL.

MY THINKING ABOUT THIS

EVOLVED THROUGH A SET OF

MEETINGS AT THE INSTITUTE OF

MEDICINE AND I HAD A CHANCE

TO PARTICIPATE IN.

BUT OBVIOUSLY, THERE ARE

MANY SUBTYPES AND EVERYTHING

OVERLAPS EVERYTHING ELSE,

BUT FUNDAMENTALLY THE BAY I

AM THINKING ABOUT IT NOW IS

WE HAVE A GROUP OF CLINICAL

TRIALS THAT ARE INTENDED TO

ELUCIDATE BIOLOGICAL

MECHANISMS, AND I THINK THIS

PART IS JUST AS SCREWED UP

AS THE REST OF IT, MAYBE

EVEN MORE SO.

BUT I AM NOT GOING TO TALK

ABOUT THIS OTHER THAN IN ONE

PART OF THE TALK TO AT LEAST

TELL YOU WHAT I THINK SHOULD

BE DONE, WHETHER IT'S RIGHT

OR NOT.

THEN THERE ARE CRIMES TRIALS

TO ELUCIDATE RISK BENEFIT

BALANCE, AND THESE ARE

TYPICALLY HA WE THINK OF AS

PHASE -- LATE PHASE TWO,

PHASE THREE TRIALS IF YOU

ARE DEVELOPING A MEDICAL

PRODUCT.

BUT I DON'T THINK THEY ARE

PALMLY ANY DIFFERENT THAN

BEHAVIORAL INTERVENTIONS

THAT YOU MIGHT IMAGINE OR

TECHNICAL INTERVENTIONS

WHICH ARE INCREASINGLY GOING

TO NEED TO BE EVALUATED AS

TO THE FIELD OF PERSONAL

INFORMATION TECHNOLOGY

CONTINUES TO EVOLVE.

AND THE THIRD SET WOULD BE

TRIALS DESIGNED TO ASSESS

EFFECTIVENESS AS A SOCIETAL

AND INDIVIDUAL LEVELS.

AND I THINK TYPES TWO AND

THREE HERE ACTUALLY MERGE

TOGETHER, IF I AM RIGHT

ABOUT WHAT'S GOING TO

HAPPEN.

AND WE'RE GOING TO

INCREASINGLY SEE LOTS OF A

DISTINCTION BETWEEN RISK

BENEFIT BALANCE OF

INDIVIDUAL PRODUCTS AND

EFFECTIVENESS IN THE

COMMUNITY.

AND I THINK THERE ARE

BASICALLY THREE COMMON

METHODS THAT NEED TO BE DONE

TO INNOVATE.

THE VERY MOST IMPORTANT ONE

IS IMPROVED INFORMATATICS

AND BETTER USE OF QAUPT

TATIVE METHODS.

ON THE WAY UP, I WAS ON A

CONFERENCE CALL AT OUR OWN

INSTITUTION, AND THERE WAS A

BOARD CHART THAT WAS BEING

DRAWN ABOUT ONE OUR

INSTITUTIONAL ENTITIES AND

SOMEBODY SAID I DON'T SEE

INFORMATION TECHNOLOGY ON

HERE AND SOMEBODY ELSE SAID

WELL, IT'S EVERYWHERE.

AND HOW DO YOU DEPICT

EVERYWHERE ON A CHART?

IT'S A LITTLE HARD TO DO.

SO I THINK THAT THE

FUNDAMENTAL MOST IMPORTANT

ISSUE WE'VE GOT TO ADDRESS

IS GETTING PEOPLE OVER THE

HURDLE OF COLLABORATING ON

INFORMATATICS AND IN THE CTSA

PROGRAM THERE HAS BEEN THIS

DISCUSSION ABOUT THE

DIFFERENCE OF IT AND INFORM

INFORMATICS.

I THINK THERE IS A CRITICAL

THING TO ACKNOWLEDGE THAT

THEY AREN'T SAME BUT CLOSELY

RELATING.

THE SECOND PART I COULD JUST

AS EASILY HAVE SAID PARTS

TWO AND THREE ARE REALLY

JUST CULTURE.

THE SHARING OF OF DATA,

WHICH IS PHYSICALLY --

TECHNICALLY A NON-PROBLEM

NOW AND THE LINKING OF

INVESTIGATORS AND STUDY

PARTICIPANTS, WHO IN THE

PAST, HAVE BEEN SEPARATED

AND DISPARATE FROM EACH

OTHER FOR A VARIETY OF

CULTURAL REASONS, WHICH I AM

GOING TO ARGUE ARE NO LONGER

CONSTRUCTIVE.

AND FINALLY, AND THIS REALLY

CAME OUT.

WE HAD A MEETING OF THE

CITIES COMMITTEE MEETING DAY

BEFORE YESTERDAY, WHICH IS A

PARTNERSHIP AND A LOT OF

DIFFERENT PEOPLE ARE THERE

AND IT'S REALLY CLEAR AND

I'LL SHOW SOME SLIDES THAT

DEPICT THIS FOR YOU AT LEAST

THE WAY I'VE COME TO THINK

ABOUT IT.

IN SUCH A REGULATED INDUSTRY

IF AN ERROR IS MADE IT

BECOMES PUBLICLY KNOWN, IT

LEADS TO A SITUATION WHERE

PEOPLE ARE SO AFRAID TO TAKE

RISKS THAT THEY NEVER DO

ANYTHING NEW.

AND IF YOU BELIEVE THAT

WE'RE LETTING SOCIETY DOWN

BY NOT PROVIDING THE

EVIDENCE THAT'S NEEDED TO

MAKE DECISIONS, WE CAN'T

CONTINUE TO DO THINGS THE

WAY WE CONSUMER DO THEM BUT

WE HAVE A SET OF REGULATIONS

AND PEOPLE WHO ARE ADHERING

TO REGULATIONS THAT DEFEATS

THE ABILITY TO INNOVATE.

AND CLASSICICALLY, AS I'VE

LEARNED FROM OUR BUSINESS

SCHOOL, IF YOU ARE GOING TO

SOLVE THAT PROBLEM, YOU GOT

TO CREATE AN ENVELOPE WHERE

PEOPLE CAN EXPERIMENT WITH

AGREEMENT AHEAD OF TIME THAT

IT'S OKAY TO DO THE

EXPERIMENT AND YOU ARE NOT

GOING TO BE PUNISHED FOR

TRYING, EVEN IF THINGS GO

BAD.

BUT IT'S REALLY -- AS MANY

OF YOU KNOW, A LOT OF MY

WORK IS CONDUCTING

LARGE-SCALE CLINICAL TRIALS

THAT ARE INDUSTRY-FUNDED AND

MULTINATIONAL.

AND IT'S ALWAYS FASCINATING

FOR ME TO BE IN A ROOM WITH

A BUNCH OF F.D.A. PEOPLE AND

INDUSTRY PEOPLE, ALL OF WHOM

PRETTY MUCH KNOW WHAT NEEDS

TO BE DONE.

THEY'RE ALL REALLY SMART AND

HIGHLY MOTE VIOLATED FOR THE

SAME THINGS, BUT THE DANCE

BETWEEN THE PEOPLE DOING THE

TRIALS AND THE PEOPLE WHO

ARE CHARGED WITH REGULATING

THE PEOPLE DOING THE TRIALS

LEADS TO A SITUATION WHERE

THE REAL CONVERSATIONS ARE

ALMOST IMPOSSIBLE TO HAVE

BECAUSE IT OPENS UP RISK OF

BEING MISINTERPRET THE AND

THEN HAVING THE PUNISHMENT.

SO IN ORDER FOR THESE THINGS

TO HAPPEN, THERE IS SOME

REALLY FUNDAMENTAL ISSUES

THAT ARE GOING TO HAVE TO BE

ADDRESSED CULTURALLY THAT

ARE TOUGH.

SO IN THIS MEETING, WE HAD A

LIST OF BARRIERS BECAUSE

SAENGS ESSENTIALLY WHAT

HAPPENED IN THIS MEETING IS

WE HAD REACHED AN AGREEMENT

ON INCREMENTAL ADVANCES

WHICH WE'D BEEN WORKING ON

FOR THREE YEARS IN THIS

PARTNERSHIP OR NOT ENOUGH.

ALTHOUGH I WOULD SAY THAT

WE'VE MADE GREAT PROGRESS.

FOR EXAMPLE, THIS OLD THING

THAT USED TO HAPPEN TO

INVESTIGATORS IN THE U.S.

WHERE THEY WOULD GET

INUNDATED WITH ADVERSE

REPORTS.

ONCOLOGISTS UP TO $300 A

MONTH.

MOSTLY FROM CLINICAL TRIALS

IN WHICH THEY WERE NOT

PARTICIPATING BECAUSE OF AN

INTERPRETATION OF AN F.D.A.

REGULATION THAT A GLOBAL

COMPANY WOULD HAVE TO SEND

ADVERSE EVENTS FROM

YUGOSLAVIA TO ALL OF ITS

INVESTIGATORS INVESTIGATING

THEIR PRODUCT.

AS SIMPLE AS THAT SOUNDS, IT

TOOK A YEAR TO GET THAT

TAKEN CARE OF.

SO THERE ARE MANY OTHER

THINGS LIKE THAT THAT WE'RE

FIXING.

BUT IT'S NOT GOING TO BE

ENOUGH.

AND SO WE HAD A LONG LIST OF

BARRIERS THAT HAVE TO BE

OVERCOME.

THEY HAVE SORT OF BOILED

DOWN TO THESE THREE THINGS.

OUR OWN HEALTH SYSTEMS IN

THE U.S. ARE NOT SUPPORTING

CLINICAL RESEARCH, AND IN

OUR BEST ACADEMIC CENTERS,

WHEN YOU GO AND TALK TO

INVESTIGATORS FOR THE MOST

PART THEY FEEL LIKE THEIR

OWN HEALTH SYSTEMS ARE

WORKING AGAINST THEM WHEN

THEY TRY TO DO CLINICAL

RESEARCH.

PETE ROSENBERG AND I ARE

WORKING TOGETHER ON A TRIAL

WHICH IS A HIGH-PROFILE

STUDY OF RANDOMIZED TRIAL OF

GENETIC TESTING AND THE USE

OF WAR FRIN.

AND THE TALES OF WHAT WE'VE

HEARD FROM OUR BEST ACADEMIC

CENTERS ABOUT WHAT IT TAKES

TO RECRUIT A PATIENT IN THE

TRIAL IS JUST ASTOUNDING AND

COULD BE OVERCOME IF THE

HEALTH SYSTEMS HAD IT AS

PART OF THEIR MISSION TO

HELP MAKE THIS HAPPEN.

I'VE TALKED ABOUT THE

CURRENT PENALTY FOR REGULAR

REGULATIONS AND WE HAVE TO

ACKNOWLEDGE THAT DESPITE THE

EFFORTS OF MANY PEOPLE, THE

PUBLIC TRUST HAVE AS

MEASURED BY POLLS IS

CONTINUING TO ERODE.

AND WHAT'S GOTTEN

INTERESTING THIS -BTHIS IS

IT'S NOT JUST PUBLIC

MISTRUST OF FARMA.

THIS IS NOW GOTTEN HEAVILY

INTO PUBLIC MISTRUST OF THE

F.D.A..

GOT NEWS FOR YOU IS THAT

MOST PEOPLE STILL DON'T KNOW

WHAT THE NIH IS, BUT --

[LAUGHTER]

THE SORT OF RESEARCH BRANCH

OF THE FEDERAL GOVERNMENT IS

NOT HELD IN SUCH DISREPUTE

BY THE PUBLIC AT THIS POINT.

ALTHOUGH, WE'RE REALLY

WORRIED THAT ACADEMIC

CENTERS NOW ABOUT OUR OWN

PUBLIC PERCEPTIONS.

SOMETIMES FEDERAL GOVERNMENTERED

BY -- FOSS TERED BY

DISASTERS WE HAD AT OUR OWN

MEDICAL CANCER WE HAD A

COUPLE YEARS AGO WITH CANCER

GENOMIC TESTING.

MOST OF YOU KNOW ABOUT THE

HISTORY OF CLINICAL TRIALS,

BUT I FEEL COMPELLED TO JUST

PUT THE SLIDE IN JUST TO

MENTION THAT MODERN CLINICAL

TRIALS ARE NOT ALL THAT OLD.

AND THERE IS SORT OF A SLOW

STARTUP, ALTHOUGH IT'S

FASCINATING THAT SOME OF THE

EARLIER CLINICAL TRIALS WERE

SOME OF THE MOST HE WILL

GALLANT -- ELEGANT BECAUSE

THEY WERE SO SIMPLE AND THEY

ANSWERED QUESTIONS DIRECTLY.

BUT A VERY IMPORTANT PART OF

THE HISTORY OF CLINICAL

TRIALS THAT WE DON'T TALK

ABOUT ENOUGH, ESPECIALLY

WITH TODAY'S POLITICIANS, IS

THAT THERE WAS A TIME WHEN

THERE WAS NO REQUIREMENT

THAT A MEDICAL PRODUCT BE

SHOWN TO BE EFFECTIVE BEFORE

IT CAME ON THE MARKET OR TO

KEEP IT ON THE MARKET.

AND BUT DUE TO SOME

CATASTROPHES, THERE WAS A

LAW PUT INTO PLACE AND MY

FRIEND BOB TEMPLE SPENT A

GOOD PART OF HIS EARLY

CAREER TAKING PRODUCTS OFF

THE MARKET THAT HAD NO

EVIDENCE THAT THEY WERE

EFFECTIVE.

BUT THIS LED TO A SITUATION

WHERE TO A LARGE EXTENT THE

WAY WE DO CLINICAL TRIALS IS

DICTATED BY VIEWS AT THE

F.D.A..

SINCE A VAST EMERGENT OF

CLINICAL TRIALS ARE FUND BID

INDUSTRY AT THIS POINT, AND

OFTEN MULTINATIONAL.

AND SO I THINK ONE OF THE

PROBLEMS THAT HAS HAPPENED

IS THAT FOR A VAET OF

REASONS, MUCH OF WHAT

DICTATES THE GENERAL

CONSTRUCTS OF CLINICAL

TRIALS HAPPEN IN MEETINGS

THAT OFTEN INVOLVE NO ONE

BUT INDUSTRY IN F.D.A..

AND WHILE A LOT OF IT WAS

AIRED PUBLICLY AT ADVISORY

KMETH COMMITTEE MEETINGS AND

SUCH SINCE THE MAJORITIES OF

CLINICAL TRIALS DO NOT

PROVIDE POSITIVE RESULTS FOR

THE EXPERIMENTAL TREATMENT,

MANY OF THESE EXAMPLES HAVE

NEVER SEEN THE LIGHT OF DAY

BECAUSE THERE IS NO

REQUIREMENT THAT THEY DID SO.

NOW WE HAVE CLINICAL

TRIALS.GOV, WHICH I'LL TALK

ABOUT, WHICH IS CHANGING

THAT.

BUT WE ALSO HAVE THIS

AMAZING TRANSFORMATION OF

GLOBALIZATION, WHERE PEOPLE

LIKE ME ARE CAUGHT IN THIS

SCHIZOPHRENIC STATE OF

WANTING THE U.S. TO BE THE

LEADER BUT CONSTANTLY BEING

REMINDED WE'RE ONLY FOUR

PERCENT OF THE WORLD'S

POPULATION.

AND SO WHY ON EARTH SHOULD

THE U.S. BE THE LEADER IN

CLINICAL TRIALS WHEN PEOPLE

LIVE IN OTHER COUNTRIES?

AND I THINK THE CULTURAL

ADAPTATION OF THAT IS A

MAJOR PART OF WHAT IS

HAPPENING.

AND THEN, OF COURSE, NOW WE

HAVE THE PERCENTAGIZED

MEDICINE EFFORT, WHICH IN MY

VIEW, OBVIOUSLY HOLDS GREAT

POTENTIAL BUT IN MANY WAYS

THE HYPE ABOUT PERSONALIZED

MEDICINE IS UNDERCUT THE

BASIS FOR THE NEED TO DO

CLINICAL TRIALS.

AND I THINK INCORRECTLY SO

AND I BELIEVE MASSIVELY

INCORRECTLY SO TO THE POINT

THAT IT'S GETTING A BIT

DANGEROUS THE WAY

POLITICIANS ARE THINKING

ABOUT THE WAY THE SYSTEM

COULD WORK.

OKAY, SO NOW, I AM GOING TO

START WITH WHAT I REGARD AS

A SUCCESS STORY AND PROBABLY

JUST BECAUSE I WAS INVOLVED

IN IT.

BUT I AM GOING TO GIVE YOU

THREE EXAMPLES AND THE

QUESTION THAT I CONTINUE TO

THINK ABOUT, PARTICULARLY

NOW THAT I AM CHARGE WITH

DEALING WITH ALL AREAS OF

RESEARCH AT OUR OWN

INSTITUTION AND INVOLVED IN

MANY EFFORTS IS WHY DOES

THIS WORK IN SOMEUATIONS --

SITUATIONS AND NOT IN

OTHERS?

SO WE HAD THIS PROBLEM

CALLED HEART ATTACK AND IT

JUST SO HHAPPENED I FINISHED

MY FELLOWSHIP AND I WANTD TO

BE A CCU DIRECTOR.

IT'S PRETTY EXCITING.

BUT YEAR I STARTED, PEOPLE

WOULD ROLL IN THE DOOR.

WE WOULD GIVE THEM MORPHINE

AND NITROGLICERINE, MAYBE.

WE ARGUED ABOUT IT AND WE'D

PUT THEM TO BED AND WE

DIDN'T KNOW WHAT TO DO OTHER

THAN THAT.

IF THEY HAD FRIBILLATION,

YOU WOULD APLY SOME AND THEY

MIGHT COME BACK.

AND THEN MIRACLECULOUS IN

THAT FIRST YEAR THE FIRST

ANGIOGRAMS WERE PRODUCED AND

WE COULD SEE THAT IT WAS

ACTUALLY A BLOOD CLOT IN

THERE AMAZINGLY ENOUGH.

YOU WOULD HAVE WE WOULD HAVE

FIGURED THAT OUT BEFORE BUT

IT HEPATOBEEN FIGURED OUT.

AND THE MORTALITY RATES WERE

EXTRAORDINARILY HIGH AND SO

A BUMP OF TREATMENTS

DEVELOPED FOR HEART ATTACK

AT THAT POINT, AND IT REALLY

PRETTY MUCH DID HAPPEN LIKE

THIS.

I THINK MAYBE BECAUSE WE HAD

A CLEAR TARGET AND THEN

THERE ARE SOME CULTURAL

FACTORS THAT I'LL MENTION.

PEOPLE SAID OKAY, WE HAVE A

TARGET.

IT'S A BLOOD BLOOD CLOT.

THERE ARE SOME OLDER DRUGS

AND LET'S TRY THEM OUT IN

HEART ATTACK.

NIH WAS VERY INVOLVED IN THE

EARLY TIMMY TRIALS AND THE

EARLY PART OF THIS EFFORT,

BUT VERY QUICKLY DUE TO

PRESSURE FROM THE F.D.A.,

ACTUALLY, AND DUE TO A GROUP

IN OXFORD, CLINICAL TRIALS

GROUP THERE, WIDELY

PUBLICIZING THE ISSUE VERY

QUICKLY WE WEPT FROM SMALL

MECHNISTIC TRIALS WHICH

CONTINUED INTO VERY LARGE

TRIALS WITH LARGE NUMBERS OF

PEOPLE THAT WERE GLOBAL IN

NATURE.

THE TECHNOLOGICAL

DEVELOPMENT THERE -- I THINK

MOST OF YOU IN THE ROOM NOT

MAKING A STATEMENT ABOUT HOW

YOU LOOK BUT YOU LOOK NOT

THAT DIFFERENT FROM ME IN

AGE.

THE TECHNOLOGICAL

DEVELOPMENT THAT MADE THIS

POSSIBLE WAS THE FAX MACHINE.

BEFORE THE FAX MACHINE, IT

WAS ALMOST IMPOSSIBLE TO DO

A GLOBAL CLINICAL TRIAL

BECAUSE JUST DEALING WITH

SHEETS OF PAPER AND

EXTENDING FROM ONE COUNTRY

TO ANOTHER TOOK FOREVER.

BUT WHAT THE FOLKS IN OXFORD

FIGURED OUT IS YOU CAN GET

ACLINATION TO TREAT A -- A

CLINICIAN TO GET A PATIENT

AND I SAW IT IN ACTION.

THEY HAD A WHOLE BUNCH OF

BRITISH LADIES AND FAXS

WOULD COME IN AND THEY WOULD

ASSIGN THE RANDOMIZED

TREATMENT USING A RANDOM

PROCESS AND THEN THE DATA

COULD BE COLLECTED ON ONE OR

TWO SHEETS OF PAPER AND A

FAX MACHINE AND CEPT BACK TO

THE CENTER AND THAT'S WHAT

LED TO THE ISIS TRIALS BEING

DONE WITH TENS OF THOUSANDS

OF PATIENTS, AS THEY LIKE TO

SAY.

BUT ONCE WE REALIZE THAT IT

TOOK LARGE SAMPLE SIZES TO

GET THE RIGHT ANSWERS, THAT

WAS THE NORM, AND VERY

IMPORTANTLY, THE F.D.A.

ESSENTIALLY SAID DON'T COME

IN HERE WITH YOUR LITTLE

TRIAL.

WE'RE NOT GOING TO LISTEN TO

YOU.

YOU'VE BETTER HAVE EVIDENCE

THAT YOU ARE AFFECTING THE

KEY CLINICAL END POINTS IF

YOU WANT TO GET YOUR PRODUCT

APPROVED.

AND AMAZINGLY ENOUGH,

INDUSTRY WAS ABLE TO ADAPT

TO THAT AND IT DID NOT STOP

THE DEVELOPMENT OF

TREATMENTS.

ONCE WE HAD ADEQUATE NUMBERS

OF PATIENTS AND WE HAD

DEFINITIVE ANSWERS FROM

CLINICAL TRIALS THAT, PART

OF IT MAKES CLINICAL

PRACTICE GUIDELINES REALLY

EASY BECAUSE YOU KNOW WHAT

SHOULD BE DONE.

AND WHERE YOU HAVE

DEFINITIVE ANSWERS ON WHAT

SHOULD BE DONE, YOU CAN

ABSTRACT THE GUIDELINES AND

THE PERFORMANCE MEASURES SO

YOU CAN BEGIN TO ASK THE

QUESTION IF YOU KNOW WHAT

YOU SHOULD DO, HOW OFTEN ARE

YOU ACTUALLY DOING IT?

AND I THINK A LOT OF YOU

ALREADY KNOW WHAT THE STORY

WAS THERE.

BUT WHAT'S EVOLVED NOW IS A

NATIONAL SYSTEM OF MEASURING

THE APPLICATION OF TREATMENT

THAT'S TAKEN FOR GRANTED NOW

BY EVERYONE IN THE FIELD.

SO MUCH SO THAT THE ARGUMENT

NOW ABOUT THE MAIN QUALITY

MEASURES IN THIS AREA OF

CARDIOLOGY IS ABOUT WHETHER

WE SHOULD HAVE ABANDON THE

QUALITY MEASURES BECAUSE THE

RATES OF ABUSE ARE SO HIGH

THAT THEY CAN'T BE IMPROVED.

AND SOME WORRY THAT THEY'RE

BEING OVERUSED BECAUSE

PEOPLE ARE SO ANXIOUS TO

MEET THE GUIDELINES.

SO HERE WUF YOU HAVE A

SYSTEM AND IN THE MIDDLE OF

IT IS MANAGEMENT AND

EDUCATION ABOUT THE SYSTEM.

AND MY QUESTION IS WHY DON'T

WE DO THAT IN EVERY FIELD?

IT OUGHT TO BE JUST THE

NORM, IT SEEMS LIKE.

AND TO GIVE YOU THE NUMBERS.

THESE ARE THE NUMBERS OF

PEOPLE ENCONTROLLED IN

CLINICAL -- ENROLLED IN

CRINKICAL TRIALS AND THE

RESEARCH HAS BEEN NOW BOTH

IN ACUTE CORONARY SYNDROMES

AND IN CHRONIC HEART FAILURE

THAT IF YOU JUST ADD UP THE

NUMBER OF TIMES DO YOU THE

RIGHT THING, DIVIDED BY THE

ENOUGH OPPORTUNITIES YOU HAD

TO DO THE RIGHT THING, WHAT

YOU FIND IS THAT FOR EVERY

TEN PERCENT IMPROVEMENT IN

DOING THE THING, THERE IS

ABOUT AN 11% RUCTION AND THE

REST OF YOUR PATIENTS ARE

GOING TO BE DEAD.

SO THAT'S A PRETTY

DEFINITIVE THING FOR SOCIETY

TO BE CONCERNED ABOUT BEING

DEAD.

AND YOU JUST HAVE TO ASK THE

QUESTION WHY DON'T WE DO

THIS IN EVERY FIELD?

AND MY FRIEND HARLING

CRUMHOLDS, WHO TENDS TO BE A

LITTLE TOUGH SOMETIMES ON

THE RESEARCH THAT WE DO,

MADE US REALLY HAPPY WHEN HE

DID HIS INDEPENDENT STUDY

WITH THE MEDICARE DATABASE

AND ESSENTIALLY THE BOTTOM

LINE IS YOUR RICK OF BEING

DEAD IS 40% LOWER NOW THAN

IT WAS WHEN WE STARTED.

OBVIOUSLY, A LARGE BIT OF

THIS IS DUE TO THE

BIOLOGICAL UNDERSTANDING OF

WHAT CAUSES THE PROBLEM AND

THE DEVELOPMENT OF EFFECTIVE

TREATMENTS IN A TRADITIONAL

SENSE.

BUT THE DEVELOPMENT OF A

SYSTEM OF APPLICATION AND

MEASUREMENT AS A STANDARD OF

CLINICAL CARE AND A CYCLE OF

KNOWLEDGE DERIVING FROM THAT

IS ANOTHER KEY PART OF IT.

NOW, WHAT WOULD CONTRAST

WITH?

I HAVE SO MANY EXAMPLES.

DIDN'T KNOW REALLY WHERE TO

START BUT MY FAVORITE ONE IS

-- AND THE REASON I THINK TO

ME IT'S SO INTERESTING.

IT'S REALLY TO ME THE

EQUIVALENT OF HRT IN TERMS

OF TURNING WHAT SEEMS SO

OBVIOUS ON ITS HEAD.

BUT EVERYBODY KNOWS ABOUT HRT

SO I CHOSE NOT TO TALK ABOUT

THAT.

SO HERE YOU'VE GOT A PROBLEM

WHERE THE EPIDEMIOLOGY IS

EXTRAORDINAIRELY CLEAR.

IF YOU HAVE CHRONIC KIDNEY

DISEASE, YOU GET ANEMIC AND

THE HIGHER RISK YOU ARE OF

DYING AND MOST OF THE DEATHS

ARE CARDIOVASCULAR.

SO THIS IS ACTUALLY A

MARKETING SLIDE, IN MY VIEW.

AND IT JUST MAKES SO MUCH

SENSE.

HOW COULD YOU NOT WANTS TO

MAKE THE ANEMIA GO AWAY

BECAUSE THIS WOULD FIX THE

PROBLEM?

AND SO ERITHIA PODEN WAS

DEVELOPED.

THIS WAS A MAJOR TRIUMPH FOR

BIOTECHNOLOGY AND IT WAS SO

OBVIOUS IN THE DIALYSIS

POPULATION BECAUSE THE ONLY

ALTERNATIVE WAS TRANSFUSION

FOR PEOPLE WHO WERE SEVERELY

ANEMIC THAT THE PROPER

RANDOMIZED TRIALS WERE NEVER

DONE.

AND SO THE F.D.A. APPROVED

THE TREATMENT AND HERE WE

HAD SORT OF THE ULTIMATE

EXAMPLE BECAUSE WE HAVE A

SINGLE PAIR SYSTEM IN THE

DIALYSIS POPULATION.

AND THIS MEANT THAT WHEN YOU

PUT A QUALITY MEASURE INTO

PLACE, SINCE THERE WAS ONE

PAIR, IF THAT PAIR SAID

WE'RE GOING TO PAY YOU MORE,

PEOPLE GOT PRETTY GOOD AT

MEETING THE QUALITY METRIC.

AND SO IT WAS SHOWN THAT YOU

COULD HIT THAT TARGET RANGE

WITH PERSISTENT BOMBARDMENT

OF THE PATIENT WITH HIGHER

AND HIGHER DOSES OF THIS

DRUG.

AND IN FACT, PEOPLE DID IT

QUITE WELL.

AND THIS WAS WONDERFUL

BECAUSE THE DOCTORS MADE

MORE MONEY.

THE DIALYSIS CENTERS MADE

MORE MONEY.

THE COMPANIES THAT MADE THE

DRUGS MADE MORE MONEY.

THE OM PEOPLE THAT LOST OUT

WERE THE TAXPAYERS AND THE

PATIENTS.

AND WE HAD A FELLOW WHO

THOUGHT THAT THIS WAS NOT

GOOD ENOUGH AND PROPOSED

THAT A RANDOMIZED TRIAL

NEEDED TO BE DONE, THAT

WOULD SHOW PEOPLE THAT

GIVING HIGHER DOSE WAS A

BETTER THING TO DO.

AND HE SOLD A FARMA COMPANY

TON AND THIS IS A TRUE

STORY.

WE WERE GOING TO COORDINATE

IT FROM OUR ACADEMIC MEDICAL

CENTER AND OF COURSE, WE

HAVE A CONTRACTULE

OBLIGATION THAT WE HAVE TO

HOLD THE DATABASE AND HAVE

THE RIGHT TO PUBLISH THE

RESULTS.

A CONFERENCE CALL WITH 20

PEOPLE ON THE CONFERENCE

CALL THE COMPANY LAWYERS

SAID WE'RE GOING TO GIVE

THIS FOOUR FOR-PROFIT CRO

BECAUSE IF IT'S NEGATIVE, WE

DON'T WANT IT PUBLISHED.

THAT'S WHAT THEY SAID.

SO WHAT HAPPENED, THOUGH,

WAS THE TRIAL ESSENTIALLY

FAILED ON OPERATIONAL

STANDARDS THROUGH TWO CROS

SO THEY CAME BACK TO US AND

SAID CAN YOU TAKE THIS TRIAL

OVER?

IT WAS CALLED A CHOIR TRIAL.

IT WAS A FATALLY FLAWED

TRIALS IN MANY WAYS BY THAT

TIME.

THERE WAS A LOT OF MISSING

DATA BUT AT THE VERY FIRST

LOOK THAT WE HAD OF THE DATA,

THE DATA MOMENTING COMMITTEE

HAD THEY STOPPED THE TRIAL

BECAUSE THEY SAID YOU'RE

HURTING PEOPLE WITH THIS

HIGHER DOSE TREATMENT AND

THIS IS WHAT THE PRIMARY END

POINT LOOKED LIKE.

YOU WILL NOTICE THAT THE LOW

HEMOGLOBIN GROUP HAS A LOWER

EVENT RATE THAN THE HIGHER

GROUP.

THE OPPOSITE OF WHAT WE

EXPECTED.

AND THIS WAS ACROSS A

VARIETY OF END POINTS.

YOU NOTICE DEATH ACTUALLY

ALMOST HIT A P POINT OF FIVE

IN THE WRONG DIRECTION.

IT'S ANOTHER INTERESTING

ISSUE IS WHEN OF A NEGATIVE

EFFECT OF A TREATMENT, HOW

FAR DO YOU HAVE TO GO TO

PROVE THAT IT'S NEGATIVE

BEFORE YOU STOP?

MANY INTERESTING DISCUSSIONS

ABOUT THAT.

BUT THE POINT HERE WAS THIS

TRIAL ALMOST DIDN'T GET

DONE.

IT WAS DONE TO SHOW BENEFIT

AND IT SHOWED RISK.

AND THEN FINALLY A BUNCH OF

OTHER TRIALS HAVE GOTTEN

DONE.

AND THE CUMULATIVE METAANALYSIS

IT'S PRETTY CLEAR THAT

HIGH-DOSE CSAS ARE A BAD

IDEA.

IT HAD BECOME STANDARD AND

ADOPTED EXTREMELY WELL.

SO IN THIS SCHEMEA OF HOW

TRIALS SHOULD BE DONE AND

HOW THEY SHOULD BE

INTEGRATED INTO PLAIN A

SYSTEMIC WAY.

IF YOU HAVE A SYSTEMIC

APPLICATION, YOU BETTER SURE

YOU HAVE ADEQUATE EVIDENCE

BEFORE YOU MAKE IT SYSTEMIC

BECAUSE YOU CAN DO A LOT OF

HARM IN A SYSTEMIC WAY IF

YOU DON'T HAVE THE RIGHT

EVIDENCE.

AND THE BEST SUCCESS STORY

-- I WAS TALKING TO GALE

PEARSON, ALL KNOW, IS A

PEDIATRIC ONCOLOGY.

AND IT'S STILL A MYSTERY TO

ME WHY SO MANY OTHER FIELDS

HAVE NOT ADOPTED THE MODEL

THAT WAS DEVELOPED IN

PEDIATRIC ONCOLOGY AND IT

WORKED SO WELL AND EVERYONE

ACKNOWLEDGES IT.

BUT BASICALLY, TO GO BACK TO

THE PUNCH LINE, MY VIEW OF

PEDIATRIC ONCOLOGY IS THAT

YOU HAVE A NATIONAL LEARNING

HEALTH SYSTEM WHERE PEOPLE

ARE EXPECTED TO PARTICIPATE

IN CLINICAL TRIALS AND THEY

DO IT AND THE CLINICAL

COMMUNITY IS GEARED TO LOOK

AT THE RESULTS OF CLINICAL

TRIAL AND CHANGE PRACTICE IN

A SYSTEMIC WAY.

AND THE RESULT HAS BEEN A

VERY DRAMATIC EFFECT ON

MORTALITY PER 100,000

CHILDREN.

OKAY, SO WHAT ABOUT SOME

MORE SPECIFIC PROBLEMS ABOUT

THE DIFFERENT PHASES OF

RESEARCH?

AND WE'RE TALKING ABOUT THE

VALLEY OF DEATH AND END CATS

NOW AND HOW IT'S GOING TO

FIX IT.

I THINK ONE OF THE REAL BIG

PROBLEMS THAT WE HAVE IS

THAT IT'S UNLIKELY THAT THIS

SCENARIO IS GOING TO CHANGE,

THAT IS, BIOLOGY IS SO

COMPLICATED THAT YOU ARE NOT

GOING TO KNOW UNTIL YOU PUT

THINGS INTO PEOPLE WHAT THE

END RESULT IS GOING TO BE.

AND WE CAN HETCH OUR BETTER

THROUGH PRECLINICAL WORK AND

SOME OF THE ENGINEERING OF

TISSUE IS GOING TO BE FAIRLY

REVOLUTIONARY IN THAT REGARD.

BUT NO MATTER WHAT WE DO FOR

THE FORESEEABLE FUTURE,

CLINICAL TRIALS ARE GOING TO

BE DONE AT DETERMINED RISK

AND BENEFIT.

AND WE GOT THIS VERY LONG

LAG TIME THAT WE ALL KNOW

ABOUT THAT'S IN PLAY, AND

GIVEN THIS LAG TIME AND THE

FACT THAT OVER HALF THE

DRUGS THAT GET ON THE MARKET

ARE FOUND TO HAVE A MAJOR

PROBLEM AFTER THEY'RE ON THE

MARKET, IT REALLY, I THINK,

FORCES THE ISSUE THAT WHAT

WE NEED TO BE THINKING ABOUT

IS INTEGRATING HUMAN SYSTEMS

BIOLOGY INTO THESE EARLY-PHASE

CLINICAL TRIALS.

AND THE POINT HERE IS THAT

IT'S EASY TO LOOK LIKE

RETROSPECTIVELY AND SAY

THERE WAS A TARGETED EFFECT

THAT WAS THERE.

THE QUESTION IS HOW DO YOU

CONSTRUCT A NATIONAL SYSTEM

OR AN INTERNATIONAL SYSTEM

THAT HAS THE INFORMATICS TO

TAKE INTO ACCOUNT AND

ANALYZE THE ABILITY WE NOW

HAVE THROUGH IMAGES AND

GENOMIC TECHNOLOGIES TO

DETECT OFF-TARGET EFFECTS?

RETROSPECTIVE ENGINEERING OF

OFF-TARGET EFFECTS OBVIOUSLY

CAN BE DONE.

THE QUESTION IS CAN WE DO IT

PROSPECTIVELY?

AND THIS IS CLEARLY GOING TO

BE COMPLICATED BECAUSE AT

LEAST AS BEST I CAN

UNDERSTAND IT, AS WE BEGIN

TO LOOK AT THE IMPACT OF A

DRUG OR A BEHAVIORAL

INTERVENTION FOR THAT MATTER,

OR AS WE ARE NOW LEARNING,

EVEN WHEN YOU DO SOMETHING

LIKE PUT A DEVICE IN A RENAL

ARTERY, EVERYTHING GOES HAY

WIRE IN MULTIPLE SYSTEMS AT

THE SAME TIME.

AND BEING ABLE TO MEASURE

THOSE THINGS SIMULTANEOUSLY

DEALING WITH INFORMATICS AND

DRAW A REASONABLE CONCLUSION

NOT TO BE DEFINITIVE BUT TO

HEDGE YOUR BET ABOUT WHAT

YOU MIGHT DO NEXT, I THINK

IS GOING TO BE THE NAME OF

THE GAME.

AND THIS HAS NOW BECOME MY

FAVORITE KIND OF PICTURE TO

LOOK AT.

FOR THOSE OF YOU WHO HAVEN'T

BEEN INVOLVED IN THIS, A LOT

OF PEOPLE ARE ENAMORED WITH

SYSTEMS PHARMACOLOGY NOW AND

ITS APPLICATION TO SYSTEMS

BIOLOGY.

WHAT'S PARTICULARLY

FASCINATING TO ME IS WE TOOK

CLINICAL TRIALS.GOV DATA

LAST TUESDAY TO THE QUESTION

OF WHAT'S THE RELATIONSHIP

AMONG PEOPLE WHO DO CLINICAL

TRIALS?

AND IT SHOWS A LOT OF THE

SAME SOCIAL PHENOMENON THAT

YOU SEE BETWEEN BIOLOGICAL

SYSTEMS.

THERE ARE COOP ARE TIVE

GROUPS AND THEY ALL BELONG

TOGETHER AND THEN THERE ARE

CONNECTORS TO THE

COOPERATIVE GROUPS AND SOME

OF THEM ARE BIG AND

CONNECTED TO MULTIPLE TRIALS

NETWORKS AND OTHERS AREN'T.

WELL, I THINK BIOLOGY IS

TURNING OUT TO BE THE SAME

WAY, WHICH IS TELLING US

THAT TO UNDERSTAND THE

BALANCE OF RICK AND BENEFIT

AND TO PREDICT IT, IT'S NOT

GOING TO BE A LINEAR

PREDICTION THROUGH ONE

SIMPLE PROOF OF MECH

NIM-TYPE APPROACH.

WE WERE ALSO TALKING EARLIER

THIS MORNING ABOUT

TRADITIONAL CHINESE

MEDICINE.

IT PROBABLY WILL INVOLVE AN

UNDERSTANDING OF MULTIPLE

INPUTS INTO THE SYSTEM

SIMULTANEOUSLY AND THE

INTERACTIONS OF THOSE

INPUTS.

SO IT ESTEEMS LIKE AN

IMPOSSIBLE PROBLEM BUT IF

YOU THINK ABOUT IT, WE NOW

CAN MEASURE THESE THINGS IN

HUMAN BEINGS.

WE'RE JUST NOT DOING IT AND

THERE IS NOT A PLACE YOU CAN

GO, INCLUDING THE CLINICAL

CENTER, WHERE THE HUMAN

CULTURAL SOCIOLOGY OF

PUTTING ALL THE PARTS

TOGETHER HAS BEEN DONE.

BUT WHAT I THINK WE REALLY

NEED IS SOMETHING THAT DOES

THIS IN MULTIPLE LEVELS.

NOW, TO LOOK AHEAD TO THE

NEXT PART, THIS IS OBVIOUSLY

GOING TO CREATE ANOTHER

PROBLEM, WHICH IS GOING TO

REQUIRE INFORMATICS, THEY'RE

EQUALLY AS COMPLEX AND THAT

IS THEY'RE ALREADY IN A

PHASE WHERE YOU GO SEE YOUR

DOCTOR, THE CHANCE THAT'S

YOUR DOCTOR CAN ASSIMILATE

EVEN THE RUDIMENTARY

INFORMATION THAT IS NOW

AVAILABLE IS PRETTY LOW.

AND NOW WE'RE GOING TO ADD

THIS COMPLEX SYSTEMS BIOLOGY

AND PREDICTION TO IT THROUGH

THE EARLY PHASE STUDIES.

AN INTERESTING AND

CHALLENGING PROBLEM.

AND MY GUAM IS THAT WHAT

WE'RE DOING RIGHT NOW IN

HUMAN MECHNISTIC STUDIES IS

LIKE THE BLIND PEOPLE AND

THE ELEPHANT.

WE'RE ALL INTERESTED IF OUR

PART OF IT AND WE LOOK AT

OUR PART OF IT AND ARE VERY

FOCUSED STUDIES BUT WE'RE

NOT PUTTING THE DATA

TOGETHER IN A WAY THAT

ENABLES US TO LOOK AT THE

WHOLE SYSTEM.

AND I THINK THAT'S GOING TO

BE IMPORTANT.

NOW, WHAT ABOUT THE EVIDENCE

TO GO TO THE NEXT PHASE?

AND I SHOW THIS OVER AND

OVER FOR A REASON BECAUSE IT

WAS SO ILLUMINATING AND THE

ISSUE HERE IS IF YOU GO TO

YOUR HEALTHCARE PROVIDER AND

YOU'VE GOT A HEALTH DECISION

OR YOU ARE HEALTHY AND YOU

WANT TO MAKE A DECISION

ABOUT YOUR HEALTH AND IT

RELATES TO CARDIOVASCULAR

DISEASE, I THOUGHT FIVE

YEARS AGO THAT WE HAD DONE

SO MUCH GOOD RESEARCHING

CLINICAL TRIALS THAT WE WERE

REALLY INFORMING PEOPLE WELL

ABOUT WHAT NEEDED -- WHAT

CHOICES THEY NEEDED TO MAKE.

AND SO WE HAD A POOR ITALIAN

FELLOW, LUGI, WOSHOWED UP

AND WE SAID WE GOT THIS

REALLY EASY PROJECT FOR YOU

THAT IS GOING TO MAKE YOU

POPULAR BECAUSE YOU ARE

GOING TO SHOW HOW GOOD WE

ARE IN CARDIOLOGY.

SO WE GOT TOGETHER WITH THE

AC.

AND LOOKED AT ALL OF OUR

GUIDELINES AND WE JUST ASKED

THE QUESTION HOW OFTEN HAD

WE MAKE A SIGNIFICANT

RECOMMENDATION ABOUT A

CHOICE, DO WE HAVE

HIGH-LEVEL EVIDENCE, THAT IS

FROM MULTIMILITARY RANDOMIZED

TRIALS OR METAANALYSIS AND

HOW OFTEN IS IT LEVEL C,

WHICH MEANS WE HAVE NO

EARTHLY IDEA BUT THERE ARE

EXPERTS, SORT OF LIKE THE

EXPERTS THOUGHT THEY KNEW.

AND THE WE ARE IS ABOUT 15%

OF THE TIME WE HAVE

HIGH-LEVEL EVIDENCE.

NOW, WITH THIS GROUP THERE

IS A LITTLE BIT OF A TRICK

HERE BECAUSE AS YOU ALL

KNOW, WHEN YOU DO A GOOD

CLINICAL TRIAL, THE NEXT

THING THAT HAPPENS IS YOU

REALIZED YOU'VE UNEARTHED

ANOTHER TEN QUESTIONS.

SO RIV ROXBAND IS EFFECTIVE

IN TREATING DEFRIBILLATION

BUT IT MAIN BE BETTER AS

MORPHINE AND NOW YOU HAVE A

WHOLE SET OF DERIVATIVE

QUESTIONS THAT NEED TO BE

ANSWERED.

BUT IT MAY BE A LITTLE BIT

UNFAIR.

SO FAR NO SPECIALTY HAS BEEN

WILLING TO STAND UP AND SAY

THEY HAVE EVIDENCE ON MORE

THAN 15 PERCENT OF THEIR

MAJOR DECISIONS.

ID TOOK A LOOK AT THIS AND

CAME OUT AT ABOUT 13

PERCENT.

THAT'S THE KURPTS STATE OF

THE EVIDENCE -- CURRENT

STATE OF THE EVIDENCE AND

WE'RE MAKING DECISIONS EVERY

DAY THAT ARE LIFE-AND-DEATH

OR CHRONICALLY IMPORTANT

KNOWING THAT IMPIRICALLY

IT'S IMPOSSIBLE TO ANSWER

THE QUESTION.

BUT JUST NOT DOING IT

BECAUSE THE WAY WE CONSUMER

DO IT IS TO EXPENSIVE THAT

WE CAN ONLY ANSWER A VERY

LIMITED NUMBER OF QUESTIONS

IN THE UNIVERSE.

IF YOU ASK WHAT PERCENTAGE

OF THE TIME ARE WE

COMPLETELY FLYING WITHOUT

INSTRUMENTS, IT'S ABOUT HALF

THE TIME.

AND I DO BELIEVE THAT

CLINICAL JUDGMENT AND EXPERT

OPINION IS BETTER THAN

RANDOM.

ON AVERAGE YOU ARE GOING TO

GET A BETTER DECISION THAT

WAY BUT WE HAVE SO MANY

EXAMPLES NOW WHERE IT'S

COMPLETELY BACKWARDS THAT I

DON'T THINK THE LEVEL OF

CONFIDENCE IN EXPERT OPINION

SHOULD BE ALL THAT HIGH.

AND THEN WE SAY OKAY, WELL,

WHAT'S GOING ON THAT IS SO

HARD TO DO THIS?

WE HAVE INDUSTRIES THAT HAVE

JUST DONE SO WELL THEY'VE

ELIMINATED ALL THE JOBS

RELATED TO THE INDUSTRIES

BECAUSE IT'S GOTTEN SO

EFFICIENT AND HERE WE HAVE

CLINICAL TRIALS MIRED IN

JUST SORT OF PATHETIC RATE

OF GETTING DONE.

AND THE PROBLEMS YOU ARE ALL

AWARE OF -- AND THIS IS JUST

SORT OF A LIST THAT WE'RE

SEEING, PARTICULARLY IN THE

U.S. -- ONE OF THE MAJOR

PROBLEMS IS WE'VE FIGURED

OUT HOW TO MAKE PROTOCOLS SO

COMPLICATED THAT NOBODY CAN

DO THEM.

[LAUGHTER]

AND THIS HAS BEEN DOCUMENTED

NOW MULTIPLE TIMES, AND I

THINK THE NIH IS

PARTICULARLY GUILTY OF THIS

PROBLEM RIGHT NOW.

AND THE REASONS ARE

CULTURAL.

WE ALL KNOW WHAT THEY ARE,

NOT SURE OF IT.

YOU GET A BUNCH OF EXPERTS

TOGETHER AND NO ONE WANTS TO

BE LEFT OUT.

I CALL IT THE CHRISTMAS TREE

EFFECT.

YOU START OUT WITH A

BEAUTIFUL GREEN TREE THAT

SHOULD BE ADMIRED AND THEN

EVERYBODY IN THE FAMILY

WANTS TO PUT AN ORNAMENT TON

AND NO ONE WILL TAKE GRANDMA'S

ORNAMENT OFF THE TREE AND

YOU END UP WITH A PROTOCOL,

WHICH IS IMPOSSIBLE TO DO

AND IS VERY DISTRACTING FROM

ANSWERING THE QUESTION THAT

YOU HAD.

AND YOU GYNETHIS WITH --

COMBINE THIS WITH REDUCING

COMPENSATION BECAUSE OF

GLOBAL COMPETITION AND

YOU'VE GOT A REAL RECIPE FOR

NON-PARTICIPATION IN THE

U.S..

AND SO CYCLE TIME METRICS IN

THE U.S. ARE LOOKING LOUSY

AND I KNOW THROUGH THE CTSAS

MANY OF US ARE TOUTING THAT

WE SAW THIS PROBLEM.

ACHE SURE YOU WHEN WE LOOK

AT OUR COORDINATORING CENTER

IN MANY AREAS, IT DOESN'T

REALLY LOOK BETTER THAN IT

WAS.

AND WE JUST FINISHED A MAJOR

PROJECT WITH INDUSTRY AND

THEY'RE NOT SEEING THAT

THINGS ARE LOOKING BETTER IN

THE U.S. AT THIS POINT.

WHAT HAS GOTTEN BETTER IS

IRB TIMES.

WE'VE MANAGED TO COMPENSATE

BY MAKING IT IMPOSSIBLE TO

GET CONTRACTS DONE.

AND SO WE SEEM TO HAVE JUST

BE CONTINUING TO FIGURE OUT

WAYS TO TAKE FOREVER TO GET

CLINIC CAL TRIALS DONE.

AND DATA FROM TUSTS, THESE

ARE THE THINGS THAT COME OUT

OVER AND OVER AGAIN.

AND SO THIS IS A SITUATION

WHERE, AS YOU KNOW, WE OFTEN

OPEN SITES FOR CLINICICAL

TRIAL AND NOT A SINGLE

PERSON GETS ENROLLED, WHICH

IS A HUGE WASTE OF TIME AND

MONEY.

WHAT'S GOTTEN INTERESTING AT

OUR ACADEMIC CENTERS IS

WE'RE NOW AND MOST OF US ARE

REQUIRED TO ACTUALLY PAY FOR

THINGS LIKE THE IRB AND I

THINK THAT ACTUALLY WOULD BE

NICE IF THIS WERE DONE FOR

ALTRUISTIC REASONS BUT IT'S

BEGINNING TO LEAD PEOPLE TO

SAY WAIT A MINUTE.

WHY ARE WE GOING TO PAY

$2,000 FOR A PROTOCOL THAT

WE ARE UNLIKELY EVER TO

ENTER A PATIENT INTO?

BUT WE'RE SEEING A LOT OF

DISPARATE AMONG PEOPLE WHO

DO CLINICAL TRIALS AND

PEOPLE TRYING IT ONCE AND

SAYING I GIVE UP BECAUSE

THIS IS JUST TOO HARD TO DO.

I LOSE MONEY FROM MY

PRACTICE.

EVEN IN ACADEMIC CENTERS AND

I'VE HEARD SEVERAL TALES

ABOUT THIS.

YOU KNOW, I HAVE A WORLD

RENOPE DIVISION CHIEF IN MY

DIVISION BUT YOUR NIH TRIAL

IS LOSING MONEY FOR OUR

DIVISION AND WE HAVE TO MEET

OUR BOTTOM LINE AND I AM

BEING TOLD EITHER DON'T DO

IT OR TRY TO CUT BACK ON THE

EFFORT YOU PUT INTO IT, CUT

CORNERS TO MEET THE COST

ALLOCATION THAT YOU HAVE.

NOW, AS PART OF OUR EFFORTS,

WE'VE DONE A LOT OF COST

ANALYSIS ABOUT CLINICAL

TRIALS, AND ADMITTEDLY THIS

IS A FOCUS OPTHE LARGE

CLINICAL TRIALS.

BUT I THINK THERE ARE BLOENS

-- LESSONS TO BE LAERPDS

HERE AND IT'S OUR BELIEF

THAT -- AND THIS IS THROUGH

SIMULATIONS TAKING A LOT OF

PEOPLE'S ACTUAL COST DATA

AND THEN APPLYING DIFFERENT

WAYS OF DOING CLINICAL

TRIALS TO IT -- IT'S OUR

BELIEF THAT YOU COULD PRETTY

MARKEDLY REDUCE THE COST OF

CLINICAL TRIALS IF YOU ARE

WILLING AND ABLE TO TAKE THE

STREAMLINE AG APPROACHES

THAT WE'VE ALL TALKED ABOUT

NOW FOR YEARS BUT HAVEN'T

IMPLEMENTED AS MUCH AS WE

SHOULD.

NOW, I THINK YOU ALL KNOW

THAT RIGHT NOW TO DO A

GLOBAL CLINICAL TRIAL WITH

INDUSTRY FOR A MAJOR

INDICATION IN A CHRONIC

DISEASE IS OVER $400 MILLION

PER CLINICAL TRIAL.

I'VE BEEN INVOLVED IN SOME

THAT HAVE BEEN OVER $1

BILLION PER CLINICAL TRIAL.

THERE IS A LOT AT STAKE IN

GETTING THE ANSWER AND THEY

CAN TAKE THE PROBLEMS AND

MULTIPLY THEM BY A BIG

FACTOR BECAUSE IF YOU DEAL

WITH 30 AGENCYS OBRECALLED

SECTION HE HE -- YOU HAVE A

RECIPE FOR THE CHRISTMAS

TREE EFFECT.

NOW BECAUSE YOU HAVE TO DO

IT IN ORDER TO MARKET YOUR

PRODUCT IN OTHER PLACES.

BUT I THINK THE MESSAGE IS

PRETTY CLEAR THAT WE COULD

DO THINGS MORE CHEAPLY IF WE

WANTED TO.

AND THEN THE GLOBALIZATION,

WHICH I DON'T THINK IS A BAD

THING.

I THINK IT'S A GOOD THING,

BUT IT'S NOT A GOOD THING IF

THE MAIN REASON IS BECAUSE

WE HAVE A DEFECTIVE AMERICAN

PRODUCT AND THEN WE APPLY

AMERICAN METHODS TO SOMEONE

ELSE'S PRODUCT THEN IT LEADS

TO EQUAL COMPLICATIONS.

THIS IS A SLIDE THAT CARLS

FADBERG WHERE HE TOOK THE

POSITION THAT THE U.S.

SHOULD BE BANED FROM

PARTICIPATION IN PHASE THREE

CLINICAL TRIALS BECAUSE WE

HAVE DEFINITIVE EVIDENCE OF

THE TREATMENT EFFECTS ARE

LESS IN THE U.S. THAN THEY

ARE IN THE REST OF THE

WORLD.

AND WE ARGUED WELL, THAT'S

BECAUSE WE GIVE BETTER

BACKGROUND TREATMENT TO

EVERYBODY SO THE TREATMENT

EFFECT WOULDN'T BE LESS.

THEY ARGUE BECAUSE NONE OF

YOUR PARTICIPANTS COMPLY

WITH THE TREATMENT.

THEY DROP OUT AT HIGHER

RATES AND YOU DON'T DO A

GOOD JOB OF COLLECTING DATA.

THERE IS PRETTY GOOD

EVIDENCE TO SHOW THAT WE ARE

FALLING BEHIND OTHER

SOCIETIES.

J.P. GARNIER, WHO IS C.E.O.

OF GSK SORT OF PUT IT VIVIDLY

FROM THEIR PERSPECTIVE WITH

A WRITE-UP TO HE GAVE ABOUT

WHAT THE PROBLEMS ARE.

AND THE LAST BULLET THERE IS

MY OWN, WHICH IS JUST TO

REMIND EVERYBODY THAT

ANOTHER GOOD REASON FOR

GLOBALIZATION IS THAT WE'RE

ONLY FOUR PERCENT OF THE

WORLD'S POPULATION AND OTHER

COUNTRIES SHOULD BE FINDING

OUT ABOUT THE RELEVANCE OF I

REPEAT VENGSS IN THEIR OWN

CULTURES AND PRACTICE

PATTERNS.

INTERVENTIONS.

BUT IF WE LOODO LOOK AT THE

REAL COST DATA, THIS IS WHAT

IT LOOKS LIKE RIGHT NOW AND

THIS IS FROM A CONSORTIUM OF

COMPANIES THAT DO GLOBAL

CLINICAL TRIALS.

WE ARE OPENING A JOINT

VENTURE IN INDIA TO DO

CLINICAL TRIALS AND THE PEM

COSTS ARE ONE FIFTH OF THE

COSTS THAT WE HAVE.

AND ALTHOUGH THERE IS A LOT

YOU COULD TALK ABOUT WITH

REGARD TO CLINICAL TRIALS IN

INDIA, THERE IS NO

QUESTIONING THAT THERE ARE

MANY PEOPLE IN INDIA WHO

WILL PROVIDE JUST AS HIGHER

QUALITY AND TECHNOLOGY IN

MANY OF THE HOSPITALS NOW IS

EQUAL TO OR BETTER THAN WHAT

WE HAVE IN THE U.S..

SO THESE ARE ALL THINGS THAT

NEED TO BE CONSIDERED.

SO ONE THEORY WE'VE HAD IS

IF YOU WANT TO IMPROVE A

WHOLE ENTERPRISE, YOU SHOULD

LOOK AT THE WHOLE ENTERPRISE

AND EVERY INDUSTRY THINKS

THAT WAY.

BUT THERE WAS NO WAY TO DO

IT FOR CLINICICAL TRIALS

RELEVANT TO THE U.S. UNTIL

CONGRESS DID WHAT IT DID FOR

CLINICAL TRIALS.GOV, WHICH

IS TO MAKE IT ILLEGAL NOT TO

REGISTER YOUR TRIAL WITH

CLINICAL TRIALS.GOV OR TO

REGISTER THE RESULTS UMS YOU

HAVE A TRIAL WHICH IS EXEMED

FROM THE LEGISLATION.

AND SO IN A PROJECT THIS

WE'VE BEEN DOING WITH F.D.A.

AND NLM, WE'VE BEEN REALLY

INTERROGATING CLINICAL

TRIALS.GOV IS A DATABASE --

AS A DATABASE, AND IT'S

PRETTY AMAZING THE NUMBER OF

TRIALS THAT ARE BEING DONE.

330 A WEEK.

IS THE NUMBER GOING UP OR

STAYING STEADY?

STEADY.

SO WHEN I STARTED THIS

PROJECT, MY BELIEF WAS WE

NEED TO PUT MORE MONEY INTO

CLINICAL TRIALS AND WE

NEEDED TO DO MORE CLINICAL

TRIALS.

I JUST HAVE TO TELL YOU AND

I DON'T HAVE TIME TO SHOW

ALL THE DATA.

YOU ARE GOING TO SEE ABOUT

20 PAPERS ON THIS, MOST OF

THEM SPECIALTY-SPECIFIC.

WHAT I NOW BELIEVE IS WE'RE

DOING A BUNCH OF TRIVIAL

TRIALS THAT AREN'T ANSWERING

ANYTHING USEFUL FOR WHICH

PEOPLE ARE VOLUNTEERING, AND

IF WE JUST TOOK THE SAME

AMOUNT OF MONEY AND THE SAME

EFFORT AND PUT IT INTO THE

IMPORTANT QUESTIONS, WE

COULD PROBABLY GO A LONG WAY

TOWARDS CLOSING THE EVIDENCE

GAP.

NOW, ACTUALLY MAKING THAT

HAPPEN MAY TAKE A WHILE.

BUT I PREDICT IT WILL

BECAUSE OF THE SUNLIGHT

THAT'S GOING TO BE SHOWN ON

THIS AS CLINICAL TRIALS.GOV

GETS BETTER AND BETTER AND

EASIER FOR PEOPLE TO USE AND

ANALYZE PUBLICLY.

JUST TO LOOK AT A PAPER THAT

I THINK IS GOING TO COME OUT

SHORTLY ABOUT THE WHOLE SORT

OF OVERALL PICTURE AND AND

THIS IS FROM A SNAP SHOT

TAKEN IN THROUGH SEPTEMBER

OF 2010.

YOU CAN SEE A LOT OF I

REPEAT VENGSAL CLINICAL

TRIALS IN THE DATABASE

ALREADY.

IT MAY NOT SURPRISE MOST OF

YOU BUT IT WAS SORT OF A

SURPRISE TO ME PROBABLY

BECAUSE OF WHAT IBDONE FAIR

LIVING THAT THE VAST

MAJORITY OF THE CLINICICAL

TRIALS HAVE UNDER 500

PATIENTS AND MORE THAN HALF

HAVE UNDER 100 PARTICIPANTS

WHO ARE ENROLLED.

AND OBVIOUSLY, THERE IS A

GREAT NEED FOR PHASE ONE IN

MECHNISTIC STUDIES.

IT'S VERY IMPORTANT TO DO.

BUT AS YOU DIVE DEEPLY IN

THESE TRIALS AND ASK THE

QUESTION WAS IT REALLY A

USEFUL CLINICICAL TRIAL, WAS

THERE A CHANCE OF ANSWERING

THE QUESTION REALLY TRULY

WITH THE SAMPLE SIZE AND HOW

MANY OF THEM ARE SMALL

BECAUSE THE PLANS WERE TO

ENROLL A LARGER SAMPLE BUT

THEY NEVER REACHED?

IT'S TELLING YOU WE HAVE A

LOT OF WAYS IF THIS

ENTERPRISE IF YOU WOULD LIKE

TO ADD IT AS AN INDUSTRY.

AND THIS IS NOT JUST AN

ISSUE OF THE PHASE THAT YOU

ARE IN.

YOU CAN SEE THAT WHEN YOU

LOOK AT CLINICAL TRIALS BY

PHASE OVER TIME, WE'RE

CONTINUING TO DO A LOT OF

LITTLE, TINY CLINICAL TRIALS

AND I THINK YOU ALL SAW THE

PUBLICATION ISSUE EVEN FOR

NIH-FUNDED TRIALS ABOUT HALF

OF THESE ARE NOT BEING

PUBLISHED WITHIN TWO YEARS.

AND SO A LOT OF WORK TO DO

HERE THAT BECOMES EV

DEPARTMENT WHEN YOU LOOK AT

THE WHOLE ENTERPRISE.

NOW, THEN THE LAST PART IS

WHAT ABOUT IMPLEMENTATION

AND HERE AGAIN I WANT TO

REMIND YOU I CAN SEE YOU

LOOK DEPRESSED ALREADY.

BUT --

[LAUGHTER]

WITH THE PROBLEMS THAT I AM

GOING OVER IS BECAUSE WE'VE

REACHED A POINT BECAUSE THE

EASY THINGS HAVE BEEN DONE

AND WE'RE CONTINUING TO SEE

THIS REDUCTION IN DEATH AND

DISABILITY AND I ALWAYS FEEL

LIKE I NEED TO SHOW IT.

IT'S NOT THAT I'M POSSESS

MISTAKE.

I THINK WE NEED TO THINK

DIFFERENTLY ABOUT WHERE WE

ARE HEADING.

WE DO HAVE A PROBLEM IN THE

U.S. RELATIVE TO OTHER

COUNTRIES AND MY MOST VIVID

PICTURE OF THIS WAS IN

BEIJING WHERE THE CHINESE

MINISTER OF HEALTH, WHO SORT

OF SMILED AND SAID YOU KNOW,

PEOPLE FROM BEIJING LIVE ON

AVERAGE FOUR YEARS LONGER

THAN PEOPLE IN THE UNITED

STATES.

I SAID CAN THAT REALLY BE

TRUE?

I STILL DOUBTED STATISTICS A

LITTLE BIT BUT THERE IS

PROBABLY SOMETHING TO IT AND

RIGHT NOW WE'RE NESTLED

BETWEEN CUBA AND CHINA AT

LEAST IN TERMS OF GLOBAL

STATISTICS.

AND WE HAVE HUGE DISPARITIES

THAT ARE INCREASINGLY

OBVIOUS AND FOR REASONS I

WILL SHOW YOU THINK WILL

INCREASINGLY BE MEASURABLE

THAT WE NEED TO DEAL WITH.

AND WE ARE WHAT YOU WOULD

CALL A BAD DEAL.

THIS IS OUR BUSINESS SCHOOL

SLIDEF YOU WERE GOING TO

PURCHASE HEALTHCARE IN ANY

OF THESE COUNTRIES AND YOUR

METRIC WAS HOW MUCH DO YOU

PAY PER YEAR OF LIFE THAT

YOU ARE GOING TO LIVE, THE

U.S. WOULD BE THE VERY LAST

PLACE THAT YOU WOULD GO.

AND IF WE LOOK AT QUALITY

AMONG THE COMMONWEALTH

COUNTRIES, THIS IS THEIR

LATEST REPORT.

PINK HERE MEANS BAD.

I ENJOYED GIVING THIS

LECTURE IN TORONTO ABOUT A

MONTH AGO, AND BECAUSE THEY

LIKE TO THINK THEY ARE

DIFFERENT THAN THE U.S. AND

CANADA AND I SAID YOU ARE

JUST AS PINK AS WE ARE

ALMOST.

YOU ARE NEXT TO WORST.

AND THEY BLAMED IT ON US FOR

EXPORTING OUR BAD HABITS.

[LAUGHTER]

AND OUR COSTS TRAJECTORY.

IT'S NOT JUST THE CURRENT

COSTS PER QUALITY UNIT.

IT'S A TRAJECTORY, WHICH IS

REALLY SCARY.

WE JUST HAD AN EXERCISE AND

I WILL SHOW YOU IN A MINUTE

WHY WE CAN DO THIS.

BUT WE TAKE THE WHOLE

MEDICARE AND MEDICAID

POPULATION OF DURHAM COUNTY,

WHICH IS 260,000 PEOPLE.

MEDICARE AND MEDICAID IS

49,000.

YOU AS A TAXPAYER ARE

CURRENTLY CONTRIBUTING $430

MILLION TO THEIR HEALTHCARE.

THE 49,000 PEOPLE.

TAKING THE INMIGRATION, THE

AGING OF THE POPULATION, THE

ACCOUNTABLE CARE ACT, NOW

ESSENTIALLY MEDICAID LIKE

PEOPLE, THAT NUMBER FOUR

YEARS FROM NOW WILL BE

$760.LE IFS ITING $760

MILLION.

SOMETHING IS GOING TO HAVE

TO GIVE IN THIS EQUATION.

WHAT'S THIS NEW ENVIRONMENT

THAT COULD FOSTER THE

TRANSFORMATION?

FIRST THING THAT I THINK

PEOPLE ARE NOT REALIZING

ENOUGH -- ALTHOUGH THE NEW

PRAGMATIC CLINICAL TRIALS

RFA DID RECOGNIZE IT FROM

THE NIH -- IS THAT THERE IS

MASSIVE CONSOLIDATION

HAPPENING OF HEALTHCARE

SYSTEMS IN THE U.S., AND

CARDIOLOGY GOT TO BE THE

LEADING EDGE OF THIS BECAUSE

CMS SUDDENLY DECIDED TO CUT

OUR REIMBURSEMENT TO 26%.

WE WEPT FROM 70% PRIVATE

PRACTICE OR SELF-EMPLOYED TO

70% EMPLOYED, THAT IS OWNED

BY A HEALTH SYSTEM IN TERMS

OF OUR PRACTICE IN JUST FOUR

YEARS.

AND WHAT'S HAPPENING IS THAT

BECAUSE OF THE ECONOMIC

ISSUES PREDOMINANTLY,

PRIVATE PRACTICE, AS WE KNOW

IT, IS GOING AWAY VERY

QUICKLY AND YOU CAN SEE IT

IN THIS AREA REALLY IN AN

INTERESTING WAY.

I HADN'T THOUGHT ABOUT IT

BUT I WAS AT A MEETING FOUR

MONTHS AGO WITH A PROFESSOR

AT GW AT HEALTH POLICY AND

AS WE WERE DRIVING AROUND,

HE TOLD ME ABOUT WHAT WAS

GOING ON WITH HOPKINS BUYING

THE FOUR HOSPITALS THAT ARE

SURROUNDING THE BIG SYSTEM

THAT'S BEEN HERE -- WHAT'S

THE NAME OF IT?

MED STAR.

YEAH.

AND THEN YOU HAVE DOWN BELOW

YOU HAVE THE FAIRFAX SYSTEM,

WHICH IS ALSO CONSOLIDATING

AND BUILDING HE IS OWN

MEDICAL SCHOOL.

AND SO WHEN YOU LOOK AT IT

NOW, WHAT WE HAVE ARE UNITS

OF 15 MILLION PEOPLE.

THE UNIVERSITY OF PITTSBURGH

SYSTEM HAS GOT 15 MILLION

CUSTOMERS AND 31 HOSPITALS

THAT IT OWNS AND RUNS.

AND THEY ALMOST ALL ARE

AFFILIATED WITH A MEDICAL

SCHOOL.

SO YOU WOULD THINK IF YOUR

GOAL WAS TO HAVE A LEARNING

HEALTH SYSTEM AND NOW THERE

IS PSYCHOLOGIST AND

INTEGRATION AND A MEDICAL

SCHOOL THAT'S PART OF IT

THAT THE MEDICAL SCHOOL

WOULD BE THE BRAIN CENTER

THAT COULD SERVE AS A WAY TO

COORDINATE AND ORGANIZE

INFORMATION.

SO THAT'S A BIG SOCIETAL

CHANGE.

AND THEN WE HAVE COMPUTERS

AND HERE I HAVE TO ADMIT

THAT I AM AT GREAT RICK

BECAUSE IN 1981 MY VERY

FIRST PAPER BECAUSE I HAD

BEEN EXPOSED TO A

COMPUTERIZED DATABASE IN THE

70'S AND IT REALLY WORKED --

I PREDICTED THAT WITHIN FIVE

YEARS DOCTORS WOULD BE I

REPEAT ACTING WITH PATIENTS

WITH PERMIZED HEALTHCARE AND

USING THE COMPUTER TO

PREDICT THE BEST TREATMENT

AND THEY WOULD HAVE A

DISCUSSION AND THE RIGHT

CHOICES WOULD BE MADE.

WELL, IT'S BEEN A FEW YEARS

--

[LAUGHTER]

WE'RE STILL NOT THERE.

BUT WHAT HAS CHANGED IS

OBVIOUS.

YOU SEE IT IN THE INTERNET

TRAFFIC.

IF YOU GO TO RURAL INDIA,

YOU WILL SEE PEOPLE LIKE

THIS AND IT REALLY IS TRUE

THAT CELL PHONES WORK BETTER

IN INDIA THAN THEY DO IN

MOST OF THE U.S.

WE'RE JUST -- I HAVEN'T DONE

MUCH WORK IN THE MIDDLE EAST

BUT I HAVE NOW START FORD A

VARIETY OF REASONS.

AND IN ABDABI AND DUBAI THE

AVERAGE CELL PHONE PER

POPULATION IS THREE.

I AM NOT SURE WHAT THEY'RE

DOING WITH THREE CELL PHONES

PER PERSON, BUT -- AND SO

THIS PART IS REALLY

HAPPENING IN EVERY OTHER

SECTOR OF OUR SOCIETY.

THE TRANSFORMATION FROM AN

INTERNET-COMPUTER-BASED

SOCIETY TO A CELL PHONE

PERSONAL INSTRUMENT SOCIETY

AND SPEED OF TRANSFORMATION

IS CHANGING VERY QUICKLY AND

THE CONNECTIVENESS IS

CHANGING VERY QUICKLY.

I AM NOW BEING BEE SIEGED BY

ENGINEERING SCHOOL

PROFESSORS WHO SAY YOU KNOW,

THE CELL PHONE WILL MEASURE

YOUR TEMPERATURET WILL GIVE

YOUR HEART RATE.

YOU CAN DO YOUR EQG AND ALL

BE CEPT IN REALTIME TO YOUR

DATA CENTER.

WHY DON'T YOU WANT TO DO

THIS IS IT WHAT WOULD I DO

WITH ALL THAT INFORMATION IF

I HAD IT?

THE POINT IS THE TECHNOLOGY

HERE IS NOT THE LIMITATION.

IT'S OUR FIGURING OUT WHAT

TO DO WITH IT, WHICH I THINK

IS A KEY ROLE FOR THE NIH.

THE CONNECTIVITY IS CLEAR,

AND IF YOU ASK ME TO EXPLAIN

WHAT THE CLOUD REALLY IS,

IT'S NOT IN MY CAPACITY TO

UNDERSTAND IT BUT I THINK WE

ALL RECOGNIZE THAT ONE OF

THE BIGGEST PROBLEMS THAT WE

HAD IN CONNECTIVITY AND

VOLUME OF INFORMATION IS NOW

BEING SOLVED BY BIG FARMS OF

STORAGE INSTRUMENTS BUT ALSO

THE CREATION OF THE CLOUD,

WHICH IS DOING AWAY WITH THE

LOCAL STORAGE PROBLEM, IN

MANY CASE THAT'S WE USED TO

HAVE.

AND NOW WE HAVE THE I REPEAT

VENGS PLATFORM.

SO -- WE HAVE NOW THE

INTERVENTION PLATFORM.

YOUR CELL PHONE CAN TAKE A

PICTURE OF IT AND SEND BACK

A MESSAGE "DON'T EAT THAT."

[LAUGHTER]

AND THERE ARE COMPANIES

BEING FORMED AROUND DOING

THIS ALREADY.

AND ALL OF OUR INSTRUMENTS

AND DEVICES ARE BEING

MECHANIZED TO BE AUTOMATIC.

I HAD THE REAL THRILL TWO

YEARS AGO -- WE WERE TRYING

TO CONVINCE GOOGLE TO GET

VERY INVOLVED IN DIRECT

HEALTHCARE FOR A REASON I'LL

SHOW YOU IN A SECOND AND

THAT DAY THEY HAD SEVEN

DRIVERLESS CARS ON THE

HIGHWAY IN CALIFORNIA.

AND THEY WERE MAKING THE

ARGUMENT THAT IT'S ACTUALLY

SAFER THAN THE NUMBER OF

90-YEAR-OLDS THAT ARE

DRIVING AROUND ON THE SAME

HIGHWAYS.

WE'LL SEE.

AND THEN THE APPLICATION OF

THIS IS SOMETHING THAT WE'VE

ALL TALKED ABOUT AND I THINK

MY OLD FRIEND ERIC HAS

BECOME ONE OF THE KEY

NATIONAL SPOKESPEOPLE FOR

THIS.

ASSUMING THAT WE COULD DEAL

WITH ALL THIS INFORMATION

AND ANALYZE IT, THERE IS

NOTHING STOPPING US FROM

HAVING THE INFORMATION WE

NEED TO PERSONALIZE

INFORMATION BUT WHAT I THINK

IS GOING TO BE MORE

IMPORTANT IS THAT ONCE YOU

HAVE THESE SYSTEMS, ABILITY

TO LOOK AT AN ENTIRE

COMMUNITY CHANGES FROM THE

OLD EPIDEMIO LOGIC PERIODIC

ASSAY TO SOMETHING THAT'S

CONTINUOUS.

AND OBVIOUSLY, THIS IS

TECHNOLOGICALLY ENTIRELY

WITHIN OUR CAPABILITY NOW.

SO FOR THE PERSONAL THING,

DETECTING RESPONDERS,

NON-RESPONDERS, ALL THAT.

I THINK WE'RE ALL FAMILIAR

WITH THE CONCEPTS.

I WON'T GO INTO THE DETAILS

OF WHY I THINK IT'S ABOUT A

THOUSAND TIMES HARDER AND

WILL REQUIRE PROBABLY TWO

ORDERS OF MAGNITUDE MORE

CLINICAL TRIAL PARTICIPANTS,

WHERE AS MOST PEOPLE

PROMOTING THIS IS SAYING YOU

CAN DO TINY TRIALS AND YOU

WILL ANSWER ALL THE

QUESTIONS.

I THOUGHT ANSWER IS THE

OPPOSITE BECAUSE WHEN YOU

SEGMENT POPULATION LIKE THIS

YOU END UP WITH AN ENORMOUS

FALSE-POSITIVE RATE AND YOU

END UP WITH EVERY SEGMENT

FEEDING TO HAVE ITS OWN

CLINICAL TRIAL AND YOU END

UP WITH OVERLAP BECAUSE OF

THE HE WEREN'T SECTION OF

THE BIOLOGICAL PATHWAYS THAT

ARE GOING TO HAVE TO BE

SORTED OU.

I AM NOT WORRIED THAT MY

LIVELIHOOD IS GOING TO GO

AWAY.

BUT I THINK IT WILL BE

AMENABLE NOT JUST TO CANCER

BUT TO CHRONIC DISEASES AS

WELL AS ACUTE IMSS.

NOW, WHAT ABOUT DEALING WITH

ALL THIS DATA?

THIS IS REAL DATA THAT

ALMOST EVERYONE IN THE U.S.

GOES TO THE INTERNET FOR

HEALTH INFORMATION AND NOW

MORE INCREASINGLY TO THEIR

CELL PHONES.

I WON'T SAY WHAT THE FIRST

TWO ACTIVITIES ARE.

ONE OF THEM IS NOT GOOD.

BUT THERE ARE OTHER

ACTIVITIES THAT ARE DONE ON

THE INTERNET.

BUT THINK ABOUT DOCTORS.

81% OF DOCTORS USE A

STRAIGHT GOOGLE SEARCH NOW

WHEN THEY ARE IN THE CLINIC

TO LOOK AT MEDICAL

INFORMATION.

IT'S EXACTLY THE SAME

INFORMATION THAT PATIENTS

ARE LOOKING AT.

AND AVERAGE TIME SPENT IS

LESS THAN THREE MINUTES AND

90 PS TELL THEM DON'T GO

BEYOND THE THIRD SEARCH.

THIS IS TELLING YOU THE I

REPEAT ACTION WITH THE

COMPUTER IS NOT AT THE POINT

WHERE THIS COMPLEXITY CAN BE

ASSIMILATED AND IT'S

SOMETHING WE'RE GOING TO

HAVE TO UNDERSTAND HOW TO

DEAL WITH.

AND THE BAD NEWS FOR PEOPLE

WHO LIKE TO BE EXCITED ABOUT

FINDING A CURE FOR A DISEASE

IS THAT THE HARD WORK HERE

IS REALLY INFORMATATICS.

IT REALLY IS INFORMATICS AND

IT'S A STUDY OF THE I REPEAT

ACTION OF THE HUMAN BRAIN --

INTERACTION OF THE HUMAN

BRAIN WITH ATHESE AUTOMATED

SYSTEMS AND HOW THEY OUGHT

TO WORK.

NEITHER ONE OF THEM IS

GETTING INVESTMENT IT

CURRENTLY NEEDS TO GET US TO

THE PLACE THAT WE NEED TO

BE.

NOW, THE PUNCHLINE FOR ME

AND WHERE I THINK I AM GOING

TO SAY IN TEN YEARS I REALLY

BELIEVE WE'RE GOING TO BE

HERE BECAUSE I THINK THE

TIPPING POINT HAS ALREADY

BEEN REACHED IS THAT ALL OF

THIS INFORMATION CAN BE

EMBEDED INTO GEOSPATIAL

ARCHITECTURE.

AND WHY WOULD THAT BE

IMPORTANT?

WELL, I THINK THE REASON

IT'S IMPORTANT IS THAT I

THINK MANY OF YOU IN THE

ROOM ALREADY KNOW THAT THE

BIGGEST DETERMINEANT OF

ENHANCEMENT IS YOUR SOCIAL

CONTEXT, NOT YOUR BIOLOGY,

UNLESS YOU ARE UNFORTUNATE

ENOUGH TO BE BORN WITH ONE

OF THE FEW RARE DISEASES

THAT AFFECTS PEOPLE IN A

MAJOR WAY AT A YOUNG AGE.

AND SO IF YOU REALLY WANT TO

UNDERSTAND HOW TO INTERVENE

TO MAKE A DIFFERENCE, YOU

ARE GOING TO HAVE TO NOT

ONLY UNDERSTAND THE

INFORMATION ABOUT THE

INDIVIDUAL AND THEIR

BIOLOGY.

YOU ARE GOOFING TO

UNDERSTAND THE IMPACT OF

WHERE THEY LIVE AND WHO THEY

INTERACT WITH AND WHY THEY

DO THAT.

SO AS MANY THINGS TEND TO

HAPPEN, I WAS JUST AT A

MEETING ON CAMPUS ONE DAY,

AND MARLIN MIRANDA, WHO WAS

IN THE SCHOOL OF THE

ENVIRONMENT WAS SHOWING SOME

INFORMATION AND CONCERNED

ABOUT LEAD POISONING IN OUR

COUNTY.

AND SHE HAD FIGURED OUT THAT

BY SENDING STUDENTS AROUND

AND TAKING ALL THE PUBLICLY

AVAILABLE INFORMATION, SHE

COULD LOOK AT EVERY

HOUSEHOLD IN DURHAM COUNTY

AND FIGURE OUT THE RISK THAT

THE PIPES HAD LEAD AND ALSO

FIGURE OUT THE PROBABILITY

THAT THE PEOPLE LIVING IN

THE HOUSE WOULD DO SOMETHING

ABOUT IT ON THEIR OWN.

AND SO THIS LED TO A RISK

PROFILE AND ALSO FIGURE OUT

WHERE THE CHILDREN WERE

BEING BORN.

BECAUSE IT'S CHILDREN YOU

ARE MOST CONCERNED ABOUT.

SO THIS LED TO A PUBLIC

HEALTH SYSTEM WHERE RISKS

WERE DEVELOPED AND PEOPLE IN

THE WORST QEPTILE, THE

HIGHEST RISK OF HAVING LEAD

AND NOT DOING ANYTHING ABOUT

IT GOT A HOUSEHOLD VISIT.

PEOPLE IN THE BEST QEPT OI,

MOSTLY PROFESSORS WHO WERE

GOING TO TAKE CARE OF THEIR

OWN HOMES GOT A LETTER IN

THE MAIL AND THEN THERE WERE

THINGS THIS BETWEEN AND IT

REALLY WORKS SPECTACULARLY

WELL.

AND SO I ASKED THE QUESTION.

HAVE YOU EVER THOUGHT ABOUT

PUTTING ELECTRONIC HEALTH

DATA INTO THAT INFORMATION?

AND WE HAVE A SECRET WEAPON

IN DURHAM COUNTY, WHICH IS

THAT FOR UNUSUAL REASONS, WE

HAVE A MONOPOLY ON

HEALTHCARE DELIVERY IN

DURHAM COUNTY.

IT'S A PLACE CALLED UNC,

WHICH IS EIGHT MILES AWAY.

MY NEXT STOP FROM HERE IS

THE TOURNAMENT IN ATLANTA,

FOUR DAYS OF BASKETBALL.

THEY HAVE A MON OPPLI IN

ORANGE COUNTY NEXT DOOR AND

THERE IS OVERLAP BUT NOT AS

MUCH AS YOU WOULD THINK.

AND INTERESTINGLY YOU DUE IT

A CTSA PROJECT WE ARE TIMIDLY

SHARING HEALTH DATA BETWEEN

THE TWO SYSTEMS THAT ARE

COMPETING.

SO IN ORDER TO DO THIS, WE

HAD TO ENGAGE IN ABOUT THREE

YEARS OF VERY INTENSIVE

CHICKEN DINNERS AND CHURCHES

AND SCHOOLS ALL KINDS OF

PLACES TO BUILD PUBLIC TRUST

BECAUSE THIS STARTED VERY

SHORTLY AFTER THE LA CROSS

CASE, WHICH HAD A LOT OF

IMPLICATIONS THAT MANY OF

YOU KNOW ABOUT.

BUT THE END RESULT IS

EVERYBODY SIGNED ON.

THE PUBLIC HEALTH

DEPARTMENT, THE FEDERALLY

QUALIFIED HEALTH CENTER, THE

CONGATIONAL LEADERS, SO ON

AND SO FORTH.

AND WEIBE DONE IT NOW.

SO THAT LIKE OTHER

GEOSPATIALING PEOPLE AND AS

YOU KNOW THERE IS A LOT OF

THIS GOING ON IN MULTIPLE

DISEASES NOW -- WE CAN LOOK

AT DURHAM COUNTY AND SEE

PRETTY MUCH EVERYTHING

THAT'S GOING ON ALMOST IN

REALTIME.

SO THIS WILL BE THE TYPICAL

THING YOU WOULD LOOK AT,

WHICH IS GEOGRAPHICAL

NEIGHBORHOODS.

THIS SHOWS YOU PEOPLE,

HOUSEHOLD MEDIAN INCOME AND

PERCENT AFRICAN-AMERICAN.

BUT WHAT WE CAN DO NOW IS

LOOK AT INDIVIDUALS BY THE

HOUSEHOLD EXACTLY WHERE THEY

LIVE.

NOW, THESE DATA ARE JITTERED,

WHICH MEANS YOU COULD NOT

ACTUALLY IDENTIFY AN

INDIVIDUAL.

IT'S BEEN RANDOMLY MOVED SO

THAT THE INDIVIDUALS ARE

MOVED AROUND.

AND WE ARE NOW OVER 90

PERCENT OF THE POPULATION IN

THE SYSTEM.

SO FOR EXAMPLE, IF YOU

WANTED TO KNOW ABOUT

DIABETES, WE KNOW WE HAVE

EXACTLY 14,000,345 PEOPLE

WHO HAVE BEEN DIAGNOSED WITH

DIABETES WHO LIVE IN OUR

COUNTY AND WE KNOW EXACTLY

WHERE THEY LIVE.

AND WE KNOW EVERYTHING ABOUT

THEIR HEALTH DATA.

BUT WE ALSO KNOW ABOUT THEIR

NEIGHBORHOODS AND THEIR

ENVIRONMENTAL DATA.

SO NOW LET'S GO BACK TO THE

BEGINNING AND LET'S SAY THAT

WE HAD A QUESTION ABOUT

DIABETES.

WHY ON EARTH IF YOU HAVE A

SYSTEM LIKE THIS SHOULD IT

TAKE YOU FOUR YEARS TO

ENROLL IN A TRIAL OF

DIABETES?

YOU WOULDN'T NEED THAT MUCH

OF THE AMERICAN POPULATION

IN A SYSTEM LIKE THIS TO GO

DIRECTLY TO PEOPLE ON THEIR

CELL PHONES, GET THEM TO

AGREE TO BE INVOLVED AND

MAYBE YOU SHOULD COLLECT THE

DATA OR MOST OF IT ON THE

CELL PHONE AND THE PARTS

THAT YOU ALREADY HAVE IN THE

ELECTRONIC RECORD, WHY WOULD

YOU NEED TO RECREATE THAT IN

AN EXPENSIVE PARALLEL YUSUF

OF CLINICICAL TRIALS?

NOW, I AM NOT PROPOSING THIS

CAN BE DONE NEXT YEAR

BECAUSE A LOT OF THE ISSUES

THAT WE WERE ABLE TO

OVERCOME BECAUSE OF OUR

LITTLE EUROPE, AS I CALL IT

IN NORTH CAROLINA, IF YOU

HAVE COMPETING HEALTH

SYSTEMS.

THIS IS REALLY HARD BECAUSE

EVEN SHARING DATA BECOMES A

MATTER OF COMPETITIVE

INTELLIGENCE AND ALL KINDS

OF ISSUES COME UP.

AND THEN FAMILY, BECAUSE OF

THE WAY THE TECHNOLOGY IS

PROLIFERATING, THIS IS NOT

SOMETHING THAT'S U.S.-SPECIFIC.

SO EVEN FOR RARE DISEASES,

IF YOU THOUGHT ABOUT YOUR

RARE DISEASE THAT YOU ARE

STRUGGLING TO ENROLL A

COHORT IN IN THE U.S., MUCH

LIKE THE BUSINESSPEOPLE ARE

TELLING ME WITH MARKETING

NOW.

WE USED TO THINK OF A MARKET

AS 800 MILLION PEOPLE WHO

LIVED IN THE U.S., WESTERN

EUROPE AND SELECTIVE PEOPLE

IN THE REST.

WORLD.

BUSINESSPEOPLE ARE NOW

THINKING OF THE MARKET AS

6.35 BILLION PEOPLE.

I THINK GIVING THE

CONNECTIVITY THAT WE NOW

HAVE, AND IF YOU HAVEN'T

SEEN IT, ONE OF THE MOST

AMAZING THINGS IS TO TALK TO

THE R AND D PEOPLE AT AT&T

OR VERIZON, THEY'LL SHOW YOU

THE 11 BILLION CALLS A DAY

THEY NOW TRACK USING THE

SAME KIND OF SOCIAL NETWORKING

ANALYSIS THAT YOU SEE FOR

BIOLOGY OR FOR CLINICAL

TRIALS.

SO, HOW COULD ALL THIS

COMING TO?

WELL, WE HAVE THESE

DIFFERENT DIMENSIONS THAT WE

NEED.

I DO THINK THE

HIGH-INTENSITY MECHNISTIC

HUMAN BIOLOGY STUDIES NEED

TO BE CORDONED OFF AND TO

HIS A SEPARATE ISSUE.

FINDING VOLUNTEERS THAT

WOULD BE THE RIGHT PEOPLE TO

STUDY THE RIGHT THING COULD

USE THIS LARGER SYSTEM.

BUT I THINK EVERYTHING ELSE

COULD EASILY FIT INTO A

SYSTEM THAT WAS DRIVEN BY

COORDINATED, INTEGRATED

HEALTH SYSTEMS WITH

ELECTRONIC RECORDS THAT

SHARE DATERA.

WE NEED AN EARLY PHASE

TRIALS NETWORK.

THIS IS MORE OF A MESSAGE

FOR END CATS.

AS FAR AS I AM CONCERNED I

HOPE THAT THIS HAPPENS AND

WE GET OVER THE

INSTITUTIONAL PROBLEMS THAT

KEEP US FROM COORDINATING.

I AM GOING TO ZIP THROUGH

THIS QUICKLY TO GET TO THE

END HERE.

BUT I THINK YOU ALL KNOW THE

KINDS OF THINGS THAT COULD

UNRAVEL THIS.

AND I DON'T THINK A SINGLE

CENTER CAN DO IT.

I THINK IT NEEDS TO BE A

NETWORK OF CENTERS THAT DO

IT.

WE ARE CREATING OUR OWN MINI

VERSION, WHICH HAS BEEN

EXCITING AND FUN.

, THAT INCLUDES NORTH

CAROLINA AND SINGAPORE,

WHERE WE HAVE A MEDICAL

SCHOOL NOW, WHICH HAS ITS

OWN INTERESTS.

AND DELI, WHERE AS I SAY, WE

CAN DO EXACTLY THE SAME

STUDY WITH BETTER TECHNOLOGY

FOR ABOUT A FIFTH THE COST.

AND YOU BEGIN TO THINK ABOUT

THE IMPACT THAT HAS ON THE

KINDS OF STUDIES YOU COULD

DO, IT'S PRETTY DRAMATIC.

AND THEN WHAT ABOUT THE

EVIDENCE CHASM?

MY MAIN POINT HERE IS PLEASE

DON'T FORGET THE BASICS.

YOU WILL NOTICE WHEN YOU

TALKED ABOUT INNOVATION, I

VPT SAID THERE IS A FANCY

STATISTICAL METHOD THAT I

THINK IS GOING TO SOLVE THE

PROBLEM.

I THINK THE PALMS OF

THERAPEUTICS ARE WELL-KNOWN

AND THEY ARE NOT GOING TO

CHANGE.

THE INNOVATION I THINK NEEDS

TO BE ABOUT THE PLAYING

FIELD THAT WE'RE APPLYING

PLAGUE ON, NOT THE RULES OF

THE GAME ONCE WE'RE ON THE

PLAYING FIELD.

USE THIS TO REMIND PEOPLE

THAT WHAT SEEMS OBVIOUS

SOMETIMES IS OBVIOUS,

SOMETIMES IT'S NOT.

THESE ARE, I THINK,

FUNDAMENTAL PRIMS, MOST OF

WHAT WE DO HAS A SMALL

EFFECT AND I AM GOING TO

STOP AT THAT ONE BUT THERE

ARE OTHERS.

THEY'RE NOT GOING TO GO AWAY

NO MATTER HOW MUCH GENETIC

TARGETING THAT YOU DO AND

THE ONLY WAY TO REALLY KNOW

IS GOING TO BE TO EVALUATE

YOUR INTERVENTION AND REAL

HUMAN BEINGS ON A REAL

LIVING SYSTEM.

NOW, ONE FUN THING FOR ME IN

PREPARING THIS LECTURE WAS

TO GO BACK TO THE ROAD MAP

ALMOST TEN YEARS AGO, IT WAS

A LITTLE SCARY AND YOU ALL

REMEMBER THESE DIE GRAPS,

THOSE OF YOU WHO WERE

INVOLVED.

BUT NOTICE THE FOUR TO SEVEN

SEVEN-YEAR TIMEFRAME.

DATA STANDARD SHARES ACROSS

INSTITUTES.

FUNDING MECHANISMS BASED ON

EFFICIENCY.

SAFE HAVEN TO DO

EXPERIMENTAL THINGS.

AND THEN OVER ON THE

RIGHT-HAND SIDE EIGHT TO TEN

YEARS A COMMON MEDICAL NOMEN

CLATURE.

DATA CENTERS UPDATED IN

REALTIME.

NATIONAL REPOSITORY OF

IMAGES AND SAMPLES.

AND THEN AT THE VERY UPPER

RIGHT HAND CORNER THE GOAL

WOULD BE A NATIONAL SYSTEM

IN WHICH PATIENTS AND

FAMILIES AND INVESTIGATORS

ARE LINKED TOGETHER THROUGH

A COMMON INFORMATION SYSTEM.

AND MY ARGUMENT TODAY IS

THAT WE ACTUALLY HAVE MADE

AMAZING PROGRESS IN ALL THE

TECHNOLOGICAL PARTS OF THIS.

AND WE'VE MADE SIGNIFICANT

PROGRESS IN THE CULTURAL

PARTS, BUT THAT IS THE

ELEMENT THAT'S HOLDING US

BACK AT THIS POINT.

AND I AM SURE THERE ARE GOOD

REASONS FOR THAT.

AND MANY OF YOU WILL

REMEMBER STEVE STRAUSS.

THESE ARE HIS SLIDES.

I HELD ON TO THEM AND I

THINK HE COULD PASSIONATELY

TALK ABOUT THIS, AND IT'S

BEGINNING TO HAPPEN NOW.

ALTHOUGH IT'S STILL CULTURALLY

DIFFICULT.

THE OLD MODEL OF BEING AT

THE NIH NETWORK WITH A

SINGLE COORDINATING CENTERS

TO THINKING ABOUT

INTEROPERABLE DATA WITH

MULTIPLE COORDINATING

CENTERS OR THE PREFERRED

SYSTEM WOULD BE A NETWORK

WHERE THE NODES ALL HAD

ACCESS TO THE DATA AT THE

RIGHT TIMES TO ANALYZE AND

THERE HAS BEEN A LOT OF

PROGRESS HERE BUT WE'RE JUST

NOT QUITE THERE YET IN TERMS

OF WHAT COULD BE DONE.

ONE PLACE WHERE I THINK

AMAZING PROGRESS HAS BEEN

MADE AND IT'S GOING TO BE

REALLY INTERESTING TO WATCH

AND I HAVE TO DISCLOSE THIS

IS A PROJECT WE'VE BEEN VERY

INVOLVED WITH IS A CEPTNAL

PROJECT AND THINGS OFTEN

HAPPEN IN THE U.S. CONGRESS

SAID YOU ARE REQUIRED AS THE

F.D.A. TO ASSEMBLE 100

MILLION ELECTRONIC HEALTH

RECORDS.

AND SO THAT'S WHAT THEY'VE

TRIED TO DO AND THE CURRENT

NUMBER IS 127 MILLION

ELECTRONIC HEALTH RECORDS.

IN A SYSTEM WHICH IS ABLE TO

RETRIEVE DATA.

YOU CAN READ ABOUT IT IN THE

NEW ENGLAND JOURNALISM.

BUT I THINK ONE OF THE MOST

IMPORTANT THINGS IS TO SOLVE

THE PROBLEM THAT PEOPLE

DON'T WANT TO CONTRIBUTE

THEIR DATA IF THEY

COMPLETELY LOSE CONTROL OF

IT.

SO WHAT'S BEEN DONE IS TO

TAKE DATA PARTNERS, ALLOW

THEM TO MAINTAIN THEIR OWN

DATA, AGREE TO A SET OF

STANDARDS FOR EXCHANGE AND

THEN THROUGH A SET OF

PROTOCOLS, PUT THE

INFORMATION TOGETHER WHEN

THERE IS A GOOD REASON TO DO

IT.

THE SOCIALIST PART OF ME,

WHICH IS STAYED WOULD BE

BETTER TO HAVE ONE SYSTEM

AND DO IT ALL RIGHT.

IN AMERICA THAT'S NOT GOING

TO HAPPEN AND THAB BEEN

TRYING TO DO IT IN THE UK

FOR DECADES AND THAB MADE

SOME PROGRESS, BUT THEY'VE

RECENTLY DECLARED FAILURE AT

THEIR LATEST ELECTRONIC

HEALTH RECORD EFFORT AS A

UNIFIED SINGLE EFFORT.

SO I ACTUALLY THINK THIS IS

PROBABLY THE BEST SOLUTION

FOR OUR CULTURE.

AND THE STEP BETWEEN THIS

AND DOING CLINICAL TRIALS IS

ONLY LIMITED NOW IN MY

OPINION, BY TWO THINGS.

ONE IS IMPROVEMENT IN THE

INFORMATICS OF AGREEING TO

COMMON TERMS AND DEFINITIONS

AND TWO IS CULTURALLY

GETTING HEALTH SYSTEMS TO A

GREATER PARTICIPATE SO THAT

DOCTORS AND NURSES HAVE TIME

TO TALK TO THE PATIENTS

ABOUT BEING RANDOMIZED.

THAT SOUNDS LIKE IT OUGHT TO

BE CHIEFABLE, BUT AS WE'VE

BEEN WORKING PRETTY HARD ON

THIS THE LAST FEW MONTHS IN

CONCEPT, THAT IS THE

PROBLEM.

THE THING THAT WORKS WELL IN

SENTNAL NOW IS IT'S TOTALLY

PASSIVE, THAT IS, THE

PROVIDERS DON'T EVEN KNOW

IT'S HAPPENING.

THE DATA SUBMITTED IS

ELECTRONIC DATA FROM THE

DATA PROVIDERS WHO ARE THE

INSURERS OR THE HEALTH

SYSTEMS, DPENGEDS ON THE

CASE.

BUT NOW IF WE'RE GOING TO

HAVE TO DO INTERVENTIONAL

STUDIES, WE'VE GOT TO ADD

THIS TOUGH, CULTURAL LET.

AND SO A SYSTEM THAT LOOKED

LIKE THIS WOULD BE FAR

SUPERIOR TO WHAT WE HAVE NOW.

MULTIPLE INTEGRATED SYSTEMS,

ELECTRONIC HEALTH RECORDS

AND COMMON DATA TERMS AND

EMBEDD IN THAT DISEASE

REGISTRIES WHICH ARE TAKING

OFF IN A MAJOR WAY PARTLY

DRIVEN BY THE FACT THAT AS

PRACTICEITIONERS, WE NEED

THESE DISEASE REGISTRYS TO

DEMONSTRATE THE QUALITY OF

WHAT WE'RE DOING IN ORDER

GET PAID.

AND SO AT THE BEDSIDE IT

WOULD LOOK SOMETHING LIKE

THIS.

AND THIS TRULY F IT

HAPPENED, WOULD BE A SYSTEM

WHERE CLINICAL CARE AND

RANDOMIZED TRIALS WOULD ONLY

DIFFER BY THE FACT THAT A

COIN IS BEING FLIPPED TO

DETERMINE THE TREATMENT.

I AM GOING TO SKIP THROUGH

ADAPTED DESIGNS OTHER THAN

TO SAY THESE ARE SLIDES FROM

FARMA BUT I THOUGHT THEY

WERE REALLY GOOD.

OTHER THAN TO SAY I DON'T

THINK ADOPTIVE DESIGNS IS

GOING TO SOLVE THIS PROBLEM.

I THINK IT'S AN IMPORTANT

CHANGE IN THINKING THAT WILL

HELP INCREMLY IN A VERY

SIGNIFICANT WAY, BUT -- LET

ME GET THROUGH THIS SO I CAN

GET TO THE END.

I THINK FOR ALL KINDS OF

INTERVENTIONS, WHETHER

THEY'RE AT THE COMMUNITY

LEVEL OR THE INDIVIDUAL

LEVEL, UNDERSTANDING THE

RESPONSE RELATIONSHIP IS

GOING TO BE A CRITICAL

ISSUE.

AND BY USING ADAPTIVE

DESIGNS AND SYSTEMS SET UP

TO BE ADAPTIVE, I THINK

THERE ARE WAYS TO GET

ANSWERS KRINLELY MORE

QUICKLY AND PROBABLY MORE

RELIABLE ANSWERS ABOUT

FINDING THAT RESPONSE

RELATIONSHIP THAT TURNS OUT

TO BE CRITICAL.

AND I LIKE THIS SLIDE IN

PARTICULAR BECAUSE IT MAKES

A POINT ABOUT AN ADAPTIVE

PLAN --

[LAUGHTER]

IS NOT AN ADAPTIVE PLAIN.

THE POINT HERE IS THAT

ADAPTATION IS SOMETHING THAT

YOU BUILD IN BY DESIGN WITH

A PLAN.

IT'S NOT A MECHANISM TO

CORRECT FOR LACK OF PLANNING

OR UNDERSTANDING.

I THINK THAT'S FREEDOM

CONFUSED.

-- FREQUENTLYLY CONFUSED.

THE LAST PART, WE ARE ALL

STUCK WITH THIS GENERALIZED

ABILITY ISSUE AND WE ALL

NETHAT RIGHT NOW IT'S FAIR

FOR THE MOST PART TO LEVY

YOUR CRITICISM OF CLINICAL

TRIALS ENROLLING A SMALL

SEGMENT OF POPULATION AND

EXTRAPOLATING SO THE WHOLE

POPULATION CAN BE RISKY AND

DANGEROUS.

AND I THINK THE WAY IT TO

DEAL WITH THAT IS TO EVOLVE

AS QUICKLY AS WE CAN TO THE

KIND OF SYSTEM THAT I

DESCRIBED AND WEIBE GOTTEN A

GLIMPSE OF IT THROUGH THE

NATIONAL REGISTRYS IN HEART

DISEASE, WHERE PRETTY MUCH

NOW FOR MOST AREAS OF HEART

DISEASE THAT ARE IN THE

MAINSTREAM OF CORONARY

DISEASE IN PART IN HEART

FAILURE, THERE ARE NATIONAL

REGISTRYS THAT PEOPLE NEED

TO USE IN ORDER TO DOCUMENT

THE QUALITY.

AND SO IF WE KNOW THAT AND

WE BEGIN TO COLLECT THAT

DATA IN A SYSTEMIC WAY AND

WE ADD IN THE ELEMENTS THAT

WE WANT FOR A PARTICULAR

STUDY, THIS WOULD BE A WAY

TO PRETTY DRAMATICALLY

REDUCE THE COST OF DOING THE

CLINICAL TRIALS.

AND ONE ELEMENT THAT I THINK

NEEDS TO BE USED MUCH MORE

OFTEN IN THIS WAY IS CLUSTER

RANDOMIZATION AND THIS IS

JUST ONE REAL EXAMPLE OF HA

WE DO WITH A SOCIETY WITH

THORACIC SURGEONS A WHILE

BACK WHERE THERE WERE SIMPLE

QUESTIONS.

COULD YOU GET THE INTERM

HORACEIS ARTERIES AS OPPOSED

TO VEINS IN PRACTICE?

THERE WAS A PROGRAM THAT WAS

DONE BY PRACTICE.

BASICALLY IT WORKED, BUT THE

BEAUTY OF THIS SYSTEM, IF

IT'S A CONTINUOUS SYSTEM IS

THAT WHEN YOU FINISH A

TRIAL, YOU CAN IMMEDIATELY

SEE WHAT IS HAPPENING AFTER

THE TRIAL IS DONE.

YOU DON'T NEED A FOLLOWON

STUDY BECAUSE YOU ARE

ALREADY COLLECTING THE DATA

THAT'S TELLING YOU WHAT THE

UPTAKE IS IN PRACTICE WHEN

THE STUDY IS OVER.

OKAY, SO YOU MAY NOT BELIEVE

ANY OF THIS CAN BE DONE.

MAYBE I'M CRAZY.

I DON'T KNOW.

I THINK IT ACTUALLY CAN BE

DONE.

I THINK WE'RE OVER THE

TIPPING PUPPY.

SO WHAT'S HOLDING IT BACK?

AND HERE I THINK IT'S WORTH

THINKING ABOUT WHAT HOLDS

BACK INNOVATION IN GENERAL

IS PEOPLE STUDY INNOVATION

ARE LOOKING AT.

SO IF YOU TALKED TO CLAY

CHRISTENSEN, WHO IS THE

PERSON WHO GETS A LOT OF THE

CREDIT ABOUT WRITING ABOUT

INNOVATION FROM A BUSINESS

SCHOOL PERSPECTIVE, USUALLY

WHAT YOU HAVE IS SOMETHING

THAT PERFORMS AT A CERTAIN

LEVEL IN A TECHNOLOGY AND

THERE IS PROGRESS IN THAT

TECHNOLOGY.

THINGS GET BETTER AND I

WOULD SAY THE CLINICAL

TRIALS ENTERPRISE ON AVERAGE

HAS GOTTEN BETTER.

WE'RE DOING A BETTER JOB

THAN WE WERE TEN YEARS AGO.

INCREMENTALLY BETTER.

BUT IN MOST AREAS OF SOCIETY,

SOMETHING COMES ALONG THAT

STARTS OUT BEING WORST.

IT'S CLUNKY, MISTAKES ARE

MADE.

AND OF COURSE, THE EXAMPLE

WE ALL USE IS THE SOLID

STATE RADIO COMPARED TO THE

TRANSSIFTOR RADIO.

YOU REMEMBER THE CHEAP

JAPANESE TRANSSIFTOR RADIOS

THAT WE USED TO MAKE FUN OF

WHEN I WAS A KID.

AND OF COURSE, WHAT HAPPENED

WAS THERE WAS NO WAY THAT

YOU COULD MAKE SOLID STATE

BETTER THAN A TRANSSIFTOR

ONCE IT REACHED A CERTAIN

POINT.

BUT THAT W WAS AN UNREGULATED

MARKET-DRIVEN COMPONENT.

SO AS A RULE AND PEOPLE HAVE

LOOKED AT DISRUPTIB

INNOVATIONS THAT ARE

CHANGING THE WAY THINGS HAVE

DONE, IT'S REPLACED THE OLD

THING, NOT EVOLVED FROM THE

OLD THING.

IT'S A LITTLE ROUGH ON

PEOPLE WHO ARE HAPPY DOING

WHAT THEY'RE DOING.

AND SO WHEN YOU THINK ABOUT

THIS, THEN IN A LIGHTLY

REGULATED MARKET IT MAKES

SENSE THAT YOU COULD BE

UNDER THE RADAR SCREEN AND

YOU MIGHT HAVE A CHEAPER OR

LESS GOOD PRODUCT AND

EVENTUALLY YOU'D GET BETTER

AND YOU WOULD WANT OUT.

YOU HAVE TO GO TO BARBARA --

BUT THAT THRESHOLD IS SO

MUCH HIGHER THAT YOU'D HAVE

TO BE A FOOL TO BE THE

DISRUPTIVE PERSON BECAUSE

THE LIKELIHOOD THAT YOU

COULD GET YOUR PRODUCT TO

THE POINT WHERE IT WOULD

REPLACE THE OLD ONE IN THE

EYES OF THE PEOPLE DOING THE

PURCHASING WOULD BE QUITE

LOW.

AND I THINK THAT IS A FAUJ

PROBLEM THAT WE'RE NOW

PHASING.

-- FACING.

I THINK EVENTUALLY THIS WILL

HAPPEN BUT MY ARGUMENT IS

THERE IS A LOT AT STAKE FOR

US IN CREATING AN

ENVIRONMENT IN SELECTED

PLACES WHERE THE MISTAKES

CAN BE MADE AND IT WILL BE

OKAY BECAUSE IT'S DONE IN AN

ENVIRONMENT THAT'S PLANNED

TO BE THAT WAY.

AND THE PALM ISSUE THEN IS

-- FAUJ ISSUE IS IF I HAD TO

DESCRIBE WHAT CLINICAL

TRIALS.GOV HAS TAUGHT ME SO

FAR IN THE WORK THAT WE'VE

DONE IS IT LOOKS A LOT LIKE

THIS.

AND I'D PREFER THAT IT LOOK

LIKE THIS.

AND WHAT'S IN BETWEEN THESE

TWO THINGS IS MOSTLY

INFORMATICS AND CULTURE.

SO IN CONCLUSION THEN WE'RE

LEFT WITH THESE SAME

BARRIERS.

I THINK THEY'RE REALLY

IMPORTANT, AND I HOPE THAT

MANY PEOPLE WILL JOIN

TOGETHER AND OVERCOME THESE

BARRIERS BECAUSE A LOT OF

PEOPLE I THINK ARE SEEING

THE POSSIBILITY THAT IT'S

THERE.

AND ULTIMATELY, IN A WAY

THAT I COULDN'T HAVE

IMAGINED IT'S OBVIOUSLY

TECHNICALLY POSSIBLE THAT,

WHETHER YOU ARE A CLINICIAN

IN A RURAL VILLAGE IN CHINA

OR YOU'RE A GEORGETOWN

MEDICAL CENTER OR DUKE

UNIVERSITY, ON YOUR PERM

DEVICE IT'S GOING TO BE A

MECHANISM TO GET THE

INFORMATION THAT YOU NEED.

BUT ALSO GENERATE KNOWLEDGE

THROUGH CONTRIBUTING TO THAT

INFORMATION BASE IN A VERY

FASSILE WAY AND THAT OUR

PATIENTS AND FAMILIES WILL

BE LINKED TO THE SAME SYSTEM

BECAUSE THEY ALREADY ARE.

WE'RE JUST JUST USING GOOGLE

RIGHT NOW TO FIND OUT AND

MAKE DECISION ABOUTS WHAT WE

DO.

SO JUST FOR FUN THE LAST

COUPLE OF SLIDES.

I THINK -- I ACTUALLY DO

WORRY ABOUT THIS.

WE'VE BEEN THE ENVY OF

EVERYONE ELSE.

INCREASINGLY IN MY GLOBAL

WORK I FIND THAT PEOPLE

ADMIRE MERPS BUT WE ARE NOT

THE ENVY THAT WE USED TO BE

AND MAYBE WE SHOULDN'T BE.

BUT I WOULD LIKE THAT TO BE

THE CASE BECAUSE WE'RE

GLOBAL PARTNERS WHO ARE THE

CHIEF INNOVATORS.

SO I THINK THE PLEA TO DO

THIS IS REALLY CRITICAL AND

I THINK IN CLINICAL TRIALS

IS CRITICA.

SINCE I AM HEADED TO

ATLANTA, ALSO EMPHASIZE THAT

THE ULTIMATE WINNING TEAM IS

GOING TO BE THE ONE WITH THE

BEST TEAMWORK, NOT THE ONE

THAT CORDONS OFF ITS

ACTIVITIES AND TRIES TO KEEP

IT SEPARATE.

SO THANKS FOR LISTENING TO

THIS.

THIS IS AT LEAST MY VIEW OF

THE WORLD AND I LOOK FORWARD

TO QUESTIONS AND COMMENTS

THAT YOU HAVE.

[APPLAUSE]

>> THIS IS BEING WEBCASTED

SO IF YOU HAVE QUESTIONS,

PLEASE USE THE TWO

MICROPHONES IN THE ISLES.

-- IN THE AISLES.

>> PROBABLY THE BEST EXAMPLE

THAT I COULD THINK OF A

DISRUPTIB INNOVATION IS IN

THE DEVELOPMENT OF LAPAR

SCOPIC SURGERY.

CAN YOU DISCUSS WHAT MADE

THAT SPECIAL THAT WAS SO

RAPIDLY IMPLEMENTED AND

ACCEPTED?

>> I THINK LAPAR SCOPIC

SOERJ BRINGS UP A TOUGH

PROBLEM WE ALL SHOULD BE

WORRIED ABOUT ANDION THE

ANSWER TO THIS PROBLEM.

THE MAIN DRIVER IS PEOPLE

OBVIOUSLY WANT NON-ENVASIVE

SURGERY.

THEY DESIRE IT AND SO THERE

IS A HUGE DRIVER FROM THE

CUSTOMER PERSPECTIVE FOR

THAT TO HAPPEN.

BUT AGAINST THAT, YOU HAVE

REGULATIONS THAT MAKE IT

REALLY HARD TO DEVELOP, FOR

EXAMPLE, A NEW DEVICE AND

INCREASINGLY HARD IN THE

UNITED STATES.

AND PARMER I AM STUCK IN

BETWEEN BECAUSE I HAVE

PARMER SEEN THE RAVAGES THAT

CAN HAPPEN WHEN YOU LET A

DEVICE ENVERPT LOOSE WITHOUT

REGULATION AND PROPER

ATTENTION TO SPERM RULES.

BUT ON THE OTHER HAND, IF WE

LOOK AT OUR OWN SOERJ

DEPARTMENT, -- SURGEIERY

DEPARTMENT, SURGEONS ARE

REWARDED FOR GETTING TO THE

OPERATING ROOM ON TIME,

ADHERING TO THE REGULATIONS

AND GETTING OUT OF THE

OPERATING ROOM AT THE LOWEST

COST WHERE PATIENTS ARE

SATISFIED.

SO IF A SURGEON SAYS I HAVE

A NEW IDEA.

LET'S TRY THIS LAPAR SCOPIC

DEVICE, THE ADMINISTRATOR IN

THE OR STAYS SAYS

WINSTON-SALEM.

YOU ARE GOING TO SLOW DOWN

THE SCHEDULE AND NOW IN THE

OLD DAYS WHEN LAPAROSCOPIC

DEVICES WERE FIRST DEVELOPED,

PEOPLE DIDN'T PAY A LOT OF

ATTENTION.

PEOPLE FOOLED AROUND WITH

THEIR DEVICE ASKS THINGS

EVOLVED BECAUSE OF THAT.

SO I ACTUALLY THINK THAT IN

THE OLD DAYS THAT BARRIER

THAT I SHOWED ON THE

BUSINESS SCHOOL SLIDE WAS

PRETTY LOW RELATIVELY

SPEAKING.

IT'S GOTTEN SO HIGH NOW.

FOR EXAMPLE, IN MY ARENA,

PER CUE ATTENDANCE CARDIAC

VALVES, HUGE DEAL.

THE U.S. I THINK IT'S 54th

IN THE WORLD TO GET ACCESS

TO PER CUTANEOUS CARDIAC

VALVES BECAUSE WE'RE SO

REGULATED.

YOU COULD ARGUE MAYBE WE

DON'T WANT TO BE FIRST, BUT

SOMEWHERE IN BETWEEN.

SO I THINK THERE IS REASON

TO WORRY ABOUT OUR ABILITY

TO INNOVATE IN SUCH A

REGULATED ENVIRONMENT.

I THINK IT HAPPENED WITH

LAPAR SCOPIC SURGERY BECAUSE

THE BARRIERS WERE LOWER AT

THE TIME AND THE DEMAND WAS

HIGH.

WY ALSO NEVER UNDERESTIMATE

THE INVENTIVE IN THE

AMERICAN PEOPLE AND GETTING

WHAT THEY WANT.

I AM EXPECTING THAT PART OF

THE CELL PHONE THING THAT'S

GOING TO HAPPEN IS PEOPLE

ARE GOING TO START GOING

DIRECTLY TO THE PUBLIC TO

MAKE THINGS HAPPEN AS

OPPOSED TO THEIR TRADITIONAL

ROUTE.

>> THANK YOU VERY MUCH.

IT WAS VERY INSPIRING, AND

PROVOCATIVE AS USUAL.

I WANTED TO ASK YOU WHAT ARE

THE THOUGHTS AROUND RUNNING

A LARGE CLINICAL TRIALS IN

INDIA AND CHINA?

AS YOU EXPLAIN THERE WILL BE

A LOT OF INCEPTIVES IN TERMS

OF COST AND PROBABLY PATIENT

ADHERENCE TO THAT TREATMENT

AND SO FORTH.

YET I THINK WE COULD ALL

EXPECT IN THE SAME TIME THE

EFFECT OF THE ENVIRONMENT,

THE GENETIC MAKEUP AND OTHER

THINGS TO INFLUENCE THE

RESULTS AND HOW WOULD THE

RESULTS BE TRANSFERABLE TO

TREATING PEOPLE IN THE U.S.

OR EASTERN EUROPEAN

COUNTRIES OR THINGS LIKE

THAT?

MAYBE THE NEXIS -- NEXUS

BETWEEN --

>> I THINK YOU KNOW THIS IS

ONE MY FAVORITE TOPICS

BECAUSE IT IS SUCH A MIND

MIND-BINDING ISSUE.

AND SO AND IT'S FASCINATING

TO ME.

THERE IS A REPORT ABOUT TO

COME OUT CALLED P CAST

PRESIDENT'S COMMITTEE AND

IT'S FOCUSED ON CONCERN THAT

THE ADMINISTRATION HAD THAT

FARMA AND BIOTECH JOBS ARE

LEAVING THE U.S. AT THE RATE

OF ABOUT 10,000 A MONTH

RIGHT NOW.

MOSTLY BECAUSE OF

OFF-SHORING OF ACTIVITIES OR

AS A FRIEND PFIZER TOLD ME

THIS MORNING WHEN I WAS ON

THE PHONE WITH HIM.

ALL THE MONEY IS IN CHINA

BECAUSE THEY'RE GOING TO PAY

FOR THE STUFF WITH CHINA

MONEY.

BUT IT'S AMAZING TO ME HOW

MANY PEOPLE WHO DON'T REALLY

UNDERSTAND MEDICINE AND

CLINICAL TRIALS THINK THAT

CLINICAL TRIALS ARE LIKE A

LABORATORY EXPERIMENT WHERE

AS A FRECHED MINE SAID, THE

GREAT THING ABOUT TRANSGENIC

MICE IS THEY SHOW UP FOR THE

EXPERIMENT EVERY DAY READY

TO GO.

WHERE AS HUMAN BEINGS LIVE

IN THIS CULTURAL ENVIRONMENT

THAT I SHOWED YOU AND THE

DATA THAT WE'RE SEEING IS

PROFOUND ABOUT THE IMPACT OF

WHERE YOU LIVE ON WHAT'S

GOING TO HAPPEN TO YOU.

AND JUST TO GIVE WHAT I

THINK IS NOT TALKED ABOUT

ENOUGH IS THIS OMT TRIAL.

I THINK THAT'S RIGHT.

IT'S A TRIAL IF CHICAGO

WHERE HUD RANDOMIZED TRIAL

GABE VOUCHERS TO MOVE OUT OF

THEIR NEIGHBORHOODS OR NOT.

AND THE RESULT THEY JUST

PUBLISHED WAS ESSENTIALLY

EQUIVALENT TO THE DPP TRIAL.

AND THE OTHER INTERESTING

THING ABOUT THE TRIAL IS YOU

GOT A VOUCHER WHERE YOU

COULD MOVE ANYWHERE YOU

WANTED.

YOU DID BETTER WITH REGARD

TO OBESITY AND DIABETES AND

IF YOUR VOUCHER GAVE YOU THE

ABILITY TO MOVE TO A

PUBLICLY SUBDIZED HOUSING OM

TO A DIFFERENT NEIGHBORHOOD.

SO NOW YOU SAY WHAT ABOUT IF

PEOPLE LEAVE THE CLINICAL

TRIALS ARE JUST A LABORATORY

EXPERIMENT?

ONE ATTITUDE THAT I HEAR

FREEDOM EVEN AMONG FARMA

EXECS IS WHY NOT JUST DO

THEM IN CHINA?

IT'S A LOT CHEAPER AND YOU

GET 10,000 SUBJECTS AND GET

YOUR DATA AND YOU GET AN

ANSWER AS TO WHETHER THE

TREATMENT WORKED.

AND OF COURSE, WHAT WY SAY

IS YOU DON'T KNOW WHETHER

THAT RESULT IS GOING TO BE

EXTRAPOLATEABLE TO THE U.S.

POPULATION OR A WHOLE

VARIETY OF REASONS, SOME OF

WHICH ARE GENETIC BUT A LOT

OF OTHERS HAVE TO DO WITH

THE DIET AND THE MEDICAL

CARE SYSTEM THAT WE WORK IN.

BUT IF YOU ARE -- I'D SAY IF

YOU BELIEVE THAT, THEN EVEN

TRIALS THAT YOU DO IN THE

U.S. GIVEN THE

HETEROGENETICS, YOU'D BETTER

START THINKING ABOUT SMALL

AREA VARIATION AS WELL AS

LARGE AREA.

BUT THE GOOD NEWS HERE FROM

OUR VIEW IS THAT THE F.D.A.

HAS PRETTY MUCH DECIDED

POLICYWISE THAT FUR GOING TO

MARKET YOUR PRODUCT IN THE

U.S., YOU'VE GOT TO HAVE

SOME PROPORTION OF YOUR

POPULATION STUDIED IN THE

U.S. UNLESS YOU HAVE A VERY

STRONG REASON TO ARGUE THAT

IT'S NOT NECESSARY.

NOW, SO IF THAT'S WHAT WE

THINK IN THE U.S., WHAT DOES

THAT SAY ABOUT CHILE OR

SOUTH AFRICA OR POLAND?

SHOULD THEY HAVE A

REPRESENTATIVE SAMPLE FROM

THEIR COUNTRIES?

NOW, OF COURSE SINCE WE'RE

BUILDING A UNIVERSITY IN

CHINA THAT IS GOING TO OPEN

IN TEN MONTHS, WHAT I AM

HEARING FROM THE CHINESE IS

WE'RE SICK AND TIRED OF YOUR

DOING TRIALS IN U.S. AND

WESTERN EUROPE AND TELLING

US WHAT THE RIGHT DOSE OF A

DRUG IS.

WE'VE GOT THE MONEY SO WE'RE

GOING TO DO OUR TRIALS IF

CHINA AND WE'RE GOING TO

TELL WHAULE THE RIGHT DOSE

OF A DRUG IS AND SEE WHAT

YOU THINK ABOUT THAT.

SO THIS IS -- WHAT'S THAT?

[INDISCERNABLE]

 COULD BE APPLICABLE TO

CHINATOWN.

POSSIBLE.

THIS IS ONE OF THE MANY

REASONS WHY I THINK WE NEED

TWO ORDERS OF MAGNITUDE MORE

RESEARCH PARTICIPANTS AND

IT'S NOT POSSIBLE TO DO THAT

THE WAY WE CURRENTLY DO

CLINICAL TRIALS.

SO WE'D BETTER BE THINKING

ABOUT THIS OTHER WAY OF

DOING THINGS AT A MUCH LOWER

COST.

YES.

>> THANKS VERY MUCH FOR YOUR

COMMENTS.

I AM RICK BERSEN WITH THE

NATIONAL INSTITUTE OF

MINORITY HEALTH AND HEALTH

DISPARITIES AND A DUKE

GRADUATE, HAVING DONE

THROUGH THE TERRY SCHOOL

BEFORE IT BECAME THE TERRY

SANFORD SCHOOL.

JUST HAVE A COUPLE OF

QUESTIONS FOR YOU.

ONE IS I'D BE INTERESTED TO

HEAR YOUR THOUGHTS ON THE

PATIENT-CENTERED MOVEMENT

AND PATIENT-CENTER THE

OUTCOMES RESEARCH EFFORT.

AND HOW YOU THINK THAT MAY

PLAY INTO SOME OF THE

CHALLENGES WITHIN THE

CURRENT CLINICAL TRIAL

SYSTEM.

IN OTHER WORDS, PERHAPS

THROUGH COMMUNITY-BASED PAR

ADVERTISE PATRY RESEARCH AND

WORKING CLOSER WITH THE

COMMUNITY AND THEIR

INVOLVEMENT IN THE PROCESS

OF THE DESIGN OF CLINICAL

TRIALS.

OF COURSE, THAT WOULD PUSH

THE TIMELINES OUT BUT YOU

MIGHT GET BETTER ADHERENCE

OR BUY-IN FROM THE COMMUNITY

IN WHICH YOU ARE TRYING TO

DO THESE TRIALS.

I MEAN, I'VE WORKED IN

INDUSTRY MYSELF, SO I

UNDERSTAND THE ISSUES AROUND

COSTS AND TIMELINES.

BUT WE HAVE OFTEN, AS I

THINK YOU POINTED OUT,

NEGLECTED THE INVOLVEMENT OF

PATIENTS IN DESIGNS AND IN

THE ENTIRE PROCESS, AND SO

IS THE CURRENT MIGRATION TO

TRY TO IMPROVE THAT ISSUE

GOING TO HELP OR HURT THE

PROCESS?

I'D BE INTERESTED IN HEARING

YOUR THOUGHTS.

ANOTHER QUESTION I HAD IS

JUST THE WHOLE ISSUE OF RISK

AND TRUST IN GENERAL.

I MEAN, IT'S PARTICULARLY

THE CASE AND DISPARATE

POPULATION GROUPS THAT HAVE

SUFFERED HISTORICALLY FROM

SOME OF THESE PROBLEMS SE SO

IT'S UNDERSTANDABLE THERE

WOULD BE RISK ISSUES THERE.

BUT THE WHOLE ISSUE OF THE

CHARGE OF THE F.D.A. IN

PROTECTING THE PUBLIC FROM

RISK, WHAT'S THE THRESHOLD?

AND THAT'S A POLITICAL ISSUE

AND HOW DO YOU ADDRESS THAT

IN THE LONG RUN?

>> WELL, THOSE ARE TWO GREAT

QUESTIONS, AND SORT OF LIKE

ALL THE QUESTIONS SO FAR

IT'S IMPOSSIBLE TO HAVE A

CLEAR, EASY ANSWER.

BUT BASICALLY MY FEELING

ABOUT PATIENT REPORTED

OUTCOMES AND PATIENT-CENTERED

RESEARCH IS THAT IT'S GOING

TO BE THE ANSWER FOR I THINK

FOR THE REASONS THAT I SORT

OF WEPT THROUGH IN THE TALK.

AS WE GET INTO THIS

INFORMATION-INTENSIVE WORLD

WHERE PEOPLE ARE CONNECT THE

WAY THEY ARE, THERE IS

ALWAYS -- WITH TECHNOLOGY

THERE IS AN AADOPTION PHASE

BUT ULTIMATELY I THINK

PEOPLE DO GRAVITATE TO

AUTHORITATIVE SOURCES AS

MUCH AS THEY CAN.

AND SO I THINK FEEDBACK,

BOTH COLLECTING DATA FROM

PATIENTS OR MEMBERS OF THE

PUBLIC AND THE CASE OF

STAYING HEALTHY, KINDS OF

CLINICAL TRIALS, BOTH IN THE

DESIGN PHASE AND WHILE THE

TRIALS ARE ONGOING IS GOING

TO BE CRITICAL.

AND WE HAD AN EXAMPLE THAT

CAME UP IN CITY.

ONE OF OUR TWO-PATIENT

ADVOCATES IN THE CONSORTIUM

IS A WOMAN WHO ENTER THE A

VALLEY CLINICAL TRIAL.

SO PFO TRIAL, WHICH IS A

DEVICE TO CLOSE IT TO

PREVENT STROKE.

AND IT WAS A QUESTIONABLE

INDICATION BUT A GOOD TRIAL

TO DO.

AND THE POINT SHE MADE TO US

IS THAT WHAT HAPPENED IN THE

TRIAL WAS THE DEVICE COMPANY

DID SOME VERY BAD THINGS

THAT THEY SHOULD NOT HAVE

DONE BUT THE MAIN REASON

THEY GOT CAUGHT IS THAT THE

PATIENTS WERE COMMUNICATING

WITH EACH OTHER ON THE

INTERNET.

THEY FORMED AN INTERNET

GROUP AND THEY WERE

COMPARING EACH OTHER'S

EXPERIENCES TO WHAT WAS

BEING REPORTED FROM THE

TRIAL AND IT DIDN'T MATCH UP.

WHICH WAS AN INTERESTING WAY

OF POLICING BAD DEVICE

COMPANIES.

BUT SO I THINK THE WISDOM OF

INVOLVING PEOPLE AFTER THE

SHORT TERM PAYING PAIN OF

FIGURING OUT HOW TO DO IT IS

GOING TO BE IMPORTANT.

I WOULD ALSO POINT OUT THAT

THERE ARE WHOLE DISEASE

AREAS WHERE THE PATIENTS AND

FAMILIES HAVE TAKEN OVER.

AND WHO ARE IN CYSTIC

FIBROSEIS ARENA, YOU CAN'T

DO ONE WITHOUT THE ACEPT OF

THE FOUNDATION AND ITS

PARTICIPANTS AND YOU CAN'T

SEE PATIENTS IN LARGE SCALE

WITHOUT SUBMITTING YOUR

QUALITY DATA TO THE

FOUNDATION FOR INDEPENDENT

EVALUATION.

SO I THINK THIS IS THE WAY

THINGS ARE GOING TO GO AND I

AM IN FAVOR OF IT.

NEPS OF TRUST, I'VE HAD MANY

LESSONS IN OUR PROJECT ABOUT

IT.

AND WHAT I WOULD SAY IS THAT

AT LEAST IN MY EXPERIENCE

FAR, IF PEOPLE BELIEVE THAT

YOU ARE SINCERE AND YOU ARE

GIVING AN HONEST EFFORT,

THEY'LL GIVE YOU THE BENEFIT

OF THE DOUBT.

AND HAVING SPENT TIME IN

DURHAM, YOU WILL UNDERSTAND

THIS.

I THINK OTHER PEOPLE WITHOUT

KNOWING THE DETAILS, COULD

PROBABLY UNDERSTAND IT, TOO.

DURHAM HAS A LONG HISTORY OF

RACIAL STRIFE AND ALSO A

TOWN GOWN SHOE, WHICH PLAYS

TOGETHER IN INTERESTING

POLITICS AND SUCH.

THERE IS A GROUP CALLED THE

COMMITTEE ON THE AFFAIRS OF

BLACK PEOPLE, WHICH HAS ONLY

BLACK MEMBERS, SWISS A VERY

POWERFUL POLITICAL STRUCTURE

IN DURHAM COUNTY.

AND ONE OF MY CONCERNS WAS

THAT WHEN WE WEPT TO THEM

AND SAID WE WANT TO PUT YOUR

HEALTH RECORD DATA INTO A

SYSTEM WHERE WE CAN SEE

EXACTLY WHERE YOU LIVE AND

USE IT FOR RESEARCH AND TO

IMPROVE YOUR HEALTH, THIS

WOULD CAUSE A TREPID PROBLEM

-- TREMENDOUS PROBLEM.

ANDERSON WHO IS NOTORIOUS

FOR PUBLICLY ACCOSTING

PEOPLE, STOOD UP AND SAID

IT'S ABOUT TIME YOU TOLD US

THE TRUTH.

SHE SAID AS LONG AS WE GET

TO SEE THE DATA TOO, THIS IS

THE BEST THING TOOTHA COULD

HAPPEN TO US BECAUSE YOU PUT

US INTO THESE NEIGHBORHOODS.

THERE ARE NO GROCERY STORES

AND NO SAFE PLACES TO WALK

AND NOW WE CAN SEE IT.

AND WE ALL HAVE TO LOOK AT

IT TOGETHER AND THERE IS A

HIGHER CHANCE THAT SOMETHING'S

GOING TO BE DONE ABOUT IT IF

WE ALL HAVE TO LOOK AT IT.

BUT ALSO UNDERSTAND THAT ALL

IT TAKES IS A FEW SLIPUPS

AND THAT BUILDING OF TRUST

AND YOU CAN LOSE IT.

SO I THINK THESE THINGS ARE

INTEGRALLY TIED TOGETHER AND

A LOT OF IT TO ME IS

CONVINCING PEOPLE THAT IF

THEIR DATA ARE USED, THAT

THEY ARE GOING TO BE PER

CEPTIVELY BETTER OFF AND

THAT TIES BACK TO CENTERED

RESEARCH BECAUSE UMS THEY

ARE INVOLVED IN IT, THEY'RE

NOT GOING TO BE ABLE TO SEE

IT.

SO I KNOW I THINK IT'S

POSSIBLE TO WORK THIS OUT.

I THINK WE'RE DOING IT.

>> THANK YOU.

>> MY BACKGROUND IS IN

PEDIATRIC ONCOLOGY SO THE

ONE SLIDE THAT YOU SHOWED IS

SOMETHING THAT I LIVED IN

FOR A VERY LONG TIME AND I

THINK IT'S BEEN A REAL

EDUCATION FOR ME COMING OUT

OF THE REST OF THE WORLD

WHERE THERE IS IS A RADICALLY

DIFFERENT SCHRUR IT SEEMS TO

ME AS WE NEED MORE AND MORE

PEOPLE PARTICIPATING IN

RESEARCH, BOTH FROM THE

STANDPOINT OF ACTUALLY

GETTING THE DATA COLLECTED

TO ALSO HEALTHCARE GIVERS

AND EVERYBODY ELSE.

ONE OF THE KEY ISSUES REALLY

IS CHANGING THE CULTURE SO

THAT WE DO HAVE THE SENSE

THAT WE'RE DESCRIBING IN

TERMS OF THE I REPEAT

ACTIONS IN DURHAM.

AND IT SEEMS TO ME WE REALLY

NEED TO MAKE A REAL ATTACK

TO CREATE THAT KIND OF THING

SO THAT PEOPLE HAVE THE

SENSE THAT WE'RE ALL

EXPERIMENTAL SUBJECTS,

WHETHER WE LIKE IT OR NOT

AND THE OM ISSUE IS WHETHER

ANYBODY IS ACTUALLY DOING

NAG WITH THE DATE Y THAT'S

GOOD.

HAVE YOU THOUGHT ABOUT HOW

WE CAN MOVE THAT ALONG

BECAUSE IN ADDITION TO THE

FACT THAT WE TWAUM MADE

MAJOR STRIDES IN TERMS OF

THE CARE OF PATIENTS, THERE

WAS NO GAP BETWEEN GATHERING

THE DPALET DATA ON IMPROVED

THERAPIES AND ACTUALLY

IMPLEMENTING IT.

AND IT SEEMS TO ME THAT WE

OUGHT TO BE ABLE TO USE THAT

EXAMPLE GOING FURTHER.

OF COURSE, YOU ARE TALKING

ABOUT RARE DISEASE, SMALL

NUMBER OF PEOPLE.

BUT CAN WE STALE THAT UP --

SCALE THAT UP?

>> SO SUSAN, WHAT YOU ARE

DESCRIBING IS ONE OF THE

BIGGEST CULTURAL PROBLEMS

AND YOU AND I HAVE TALKED

ABOUT THIS BEFORE.

AND I THINK A LOT OF WHAT'S

HAPPENED IN AMERICAN MEDICAL

COLLEGE IS WE HAVE BECOME SO

CORPORATIZED.

IF YOU TALK TO PRACTICES

DOCS AND ASK A QUESTION IF

YOU COULD ANSWER THIS

QUESTION BY PARTICIPATING IN

A CLINICAL TRIAL, WOULD YOU

LIKE TO DO IT?

IN MY EXPERIENCE ALMOST 100%

SAY YES.

THEN YOU SAY OKAY, LET'S DO

IT AND THEY SAY BUT I WOULD

LOVE TO DO IT BUT IT'S GOING

TO TAKE 30 MEN'S A DAY AND

-- MINUTES A DAY AND NO ONE

WILL PAY ME FOR THAT TIME

AND SLOW DOWN OUR SHRINK AND

WHATEVER IT IS.

AND I CAN'T PRACTICALLY DO

IT.

AND THEN YOU GO TO THE

LEADERS AND I GUESS I AM ONE

OF THOSE NOW AND YOU SAY WHY

DON'T YOU MAKE THIS PART OF

YOUR INGRAIN CULTURE?

THE WE ARE IS WE'VE GOT TO

IMPLEMENT OUR ELECTRONIC

HEALTH RECORD AND WE'RE

WORRIED ABOUT OUR PAYMENT

SYSTEM AND ALL THESE OTHER

THINGS THAT GET IN THE WAY

FIRST.

SO I'VE GONE THROUGH ALL THE

PHASESu

[LAUGHTER]

AND I REALLY THINK THE

ANSWER IS GOING TO BE

PATIENT ADVOCATES.

I THINK THE CUSTOMER OF THE

SYSTEM'S GOING TO HAVE TO

SPEAK UP AND IT'S BEEN

IMPOSSIBLE TO DO THAT

BECAUSE THERE WASN'T A

VEHICLE BUT NOW BECAUSE OF

ALL THE SAME INFORMATION

TECHNOLOGY, IF YOU'VE GOT

DISH MEAN, I SAW WITH MY

SIMMER, WHEN SHE GOT --

SISTER-IN-LAW WHEN SHE GOT

BREAST CANCER, AS THAT

COMMUNITY BREAST CANCER IN

PARTICULAR HAS GOTTEN WISER,

THEY ARE NOW PROMOTING

CLINICAL TRIALS AS THE BEST

WAY TO GET YOUR CARE.

I THINK WE OUGHT TO BE --

THOSE OF US CONCERNED ABOUT

THIS PROBABLY ARE WASTING

OUR TIME BY CONVINCING OUR

DEANS AND C.E.O.S.

BUT I THINK WORKING WITH

PATIENT ADVOCATES TO DO IT

-- WHAT'S AMAZING, I GUESS

THIS COMES WITH GETTING

OLDER BUT I USED TO THINK

THAT THE OLD PEOPLE IN

CHARGE OF THINGS COULD JUST

CHANGE THEM.

BUT WHAT YOU FIND IS THE

DEANS AND C.E.O.S FEEL JUST

AS VICTIMIZED AND THEY DON'T

KNOW WHAT TO DO ABOUT IT.

I THINK THE PRESSURE FROM

THE PATIENTS TO THINK THIS

WAY IS WHAT EVENTUALLY WILL

CHANGE IT.

ONE OTHER INSIGHT IF MY LAST

TRIP TO INDIA IN ADDITION TO

ALMOST GETTING DEPORED,

WHICH IS A DIFFERENT STORY

--

[LAUGHTER]

-- I MET WITH PATIENT

ADVOCACY GROUPS IN INDIA AND

IT IS REMARKABLE TO SEE THE

DIFFERENCE CULTURALLY

BETWEEN THE UNITED STATES

AND INDIA IN THAT REGARD.

AND IF YOU SEE WHERE THEY

ARE NOW AND THEN YOU SEE

WHERE WE ARE, YOU CAN SEE

THAT THERE ACTUALLY IS

PROGRESS THAT CAN BE MADE.

SO I AM NOT TOTALLY POSSESS

MIKT ABOUT IT.

EITHER ONE.

>> ROB, THANK YOU VERY MUCH

FOR YOUR INSIGHTFUL TALK.

I AM FROM THE FOOD AND DRUG

ADMINISTRATION AND I WORK IN

THE DEVICES CENTER.

THE QUESTION I HAVE IS YOU

SHOW THE GRAPH ABOUT THE

LEVEL OF REGULATION AND THE

ABILITY TO INNOVATE.

I WOULD LIKE TO ADD

SOMETHING TO THAT GRAPH, IS

THAT THE LEVEL OF REGULATION

IS NOT CONSTANT, THAT IT

DOES MOVE UP AND DOWN IN

RESPONSE TO EITHER POLITICAL

OR RISK PERCEPTION AND RISK

PERMISSION IS -- PERCEPTION

IS OFTEN DRIVEN TO EVENTS

AND THE FREEDOM TO INNOVATE.

IT ALL TIES INTO EACH OTHER.

THEY ALL INTEGRATE AND

SOMETIMES EARLY NONA FIELD

AS IT DEVELOPS, THERE IS

LESS REGULATION IN THAT AREA.

BUT AS THINGS HAPPEN, FOR

EXAMPLE IN THE GENE THERAPY

AREA AND A VARIETY OF THINGS

-- IBBEEN AT F.D.A. FOR A

NUMBER OF YEARS AND IBSEEN

DIFFERENT THINGS HAPPEN.

AS A PRODUCT MATURES AND

THINGS HAPPEN DURING THE

DEVELOPMENT.

A PRODUCT AREA, THEN IT GETS

NOTICED IF THERE IS UNDUE

RISK AND THE REGULATION OF

THAT AREA MAY GO UP.

AND SOMETIMES PRODUCTS GO x

THE MARKET AND THERE ARE

PROBLEMS AND THE PUBLIC

PERCEPTION AND THE PUBLIC

DISCOURSE SAYS HEY, LET'S DO

SOMETHING ABOUT THAT RISK

AND THE REGULATION GOES UP.

AND SO IT TIES IN.

AND THE PUSHBACK IN THE

OTHER FRONT IS INNOVATION

AND THE NEED TO HAVE

INNOVATIVE PRODUCTS OUT

THERE AND DEVELOPING NEW

AREAS SO EARLY ON MAYBE LESS

REGULATION.

>> I THINK YOUR POINTS ARE

VERY WELL-TAKEN.

MY -- AND I THINK WITHIN THE

F.D.A., AS YOU ALL KNOW,

THERE ARE OBVIOUSLY MANY,

MANY PEOPLE STRUGGLING TO

DEAL WITH THE SHIFTS THAT

NEED TO BE MADE TO RESPOND

TO THE CIRCUMSTANCES.

AND I GUESS MY ARGUMENT IS

THAT BECAUSE WHAT YOU SAY I

THINK IS TRUE THAT IS ONE

STANDARD SHOULD NOT FIT ALL,

THE NAME OF THE GAME I THINK

AT THE F.D.A. IS TO GET

AHEAD OF THE CURVE IN TERMS

OF POLICIES THAT PROMOTE

INNOVATION WHERE IT'S NEEDED

AND SORT OF ANTICIPATE WHERE

IT'S NEEDED BUT ALSO HELP

THE PUBLIC UNDERSTAND WHEN A

RISK -- HELP THE PUBLIC

SCALE A RISK APPROPRIATELY

BECAUSE I THINK QUITE WHAT

-- ONE THING YOU ALLUDED TO

WHICH I BELIEVE TO BE TRUE

IS THAT A SINGLE EVENT CAN

CHANGE EVERYTHING WHEN THERE

IS NO RATIONALE REASON WHY

IT SHOULD.

OTHER THAN IT HAPPENS TO GET

PUBLICIZED.

AND SO I THINK IF WE ARE

GOING TO SUCCEED, WE'VE GOT

TO BE ABLE TO HAVE

DIFFERENTTIAL DELVES BASED

ON POLICIES THAT ARE

WELL-REASONED.

OR CUE JUST SAY WE NEED

GREAT LEADERS.

MAYBE THAT'S ANOTHER WAY TO

STAY.

>> ROB, MY QUESTION GOES

BACK TO THE PRIOR QUESTION

AND ANSWER.

THE PROBLEM WITH RELYING ON

PATIENT ADVOCACY GROUPS IS

THE HOPE FOR THE FUTURE IS

THAT COMPARATIVE EFFECTIVENESS

RESEARCH HAS BEEN SPUN BY

WHO KNOWS WHOM FOR POLITICAL

REASONS TO EQUAL RASHLINGSS

AND BECOME A DIRTY WORD.

I WEPT TO AN THING FOR A

GROUP WHICH INCLUDE AID FIB

ADVOCACY ORGANIZATION AND

GAVE WHAT I THOUGHT WAS

GOING TO BE THE TALK ON CER

OM TO NYPD THERE IS A LOT OF

PUSHBACK AMONGST PATIENTS

WHO DON'T UNDERSTAND CER AS

ANYTHING OTHER THAN YOU ARE

GOING TO TELL ME WHAT DRUGS

OR DEVICES I CAN OR CAN'T

AND I DON'T KNOW PROBABLY

SERM THE INSTITUTE'S IN A

BETTER POSITION BUT SOMEHOW

OF PATIENT ADVOCATES ARE

GOING TO HELP PUSH THE

RESEARCH ENTERPRISE, THERE

IS GOING TO HAVE TO BE

EDUCATION THAT CER IS NOT A

BAD THING.

AND HOW WE MADE THE ADVANCE

THAT'S WE HAVE.

>> I COMPLETELY AGREE, AND I

UNDERSTAND WHAT'S HAPPENED

WITH THE POLITICS.

IT'S ACTUALLY QUITE

REMARKABLE BECAUSE IT SEEMS

SO OBVIOUS THAT IF YOU HAD

ATRILL FIB RIGHT NOW YOU

WOULD REALLY LIKE TO KNOW IS

MORPHIEN BETTER, IS

DEBIGTRAN BETTER?

THESE ARE MESSAGE CHOICES,

AND HAVING A STROKE THAT

COULD HAVE BEEN PREVENTED

BECAUSE YOU DIDN'T KNOW

WHICH WAS BETTER WOULD SEEM

LIKE KIND OF A SILLY TING TO

LET HAPPEN.

BUT THE OPPONENTS HAVE

OBVIOUSLY POSITIONED

THEMSELVES IF SOMETHING

LOSES IN A TRIAL IT'S

WESTERN TAKE ALL.

WHEN IN FACT, A

WELL-DESIGNED TRIAL WITH A

RIGHT SAMPLE SIZE, WHICH

WOULD BE 100 TIMES LARGER

THAN MOST TRIALS THAT ARE

DONE -- IF THERE WERE

PROFILES OF PEOPLE WHO GOT

BETTER OUTCOMES WITH ONE

TREATMENT VERSUS ANOTHER,

YOU WOULD PICK THAT UP AND

WE'D ALL BE BETTER OFF.

IT'S BEEN INTERESTING TO

WATCH MY FRIENDS ON PECOREI

AS THEY TRY KNOWING WHAT

THEY KNOW AND BELIEVE TRYING

TO HOLD TO THE PARTY LINE

ABOUT WE DON'T LOOK AT

ECONOMICS AND THIS.

IT'S JUST KIND OF SILLY.

BUT THAT'S WHERE WE ARE.

SO I THINK THE ANSWER TO

THAT IS ENGAGING WITH

PATIENT ADVOCACY GROUPS.

ONE OF THE THINGS I'VE

LEARNED IN THE DURHAM COUNTY

THING, WHICH I GUESS FOR

PEOPLE WHO ARE EXTROVERTED

IS YOU KNOW THAT ANYWAY IS

SOMETIMES YOU HAVE TO SIT

THERE A LITTLE BIT OF SAYING

WHY THE HELL AM I HERE?

ANOTHER CHICKEN DINNER?

BUT THE PAYOFF IS QUITE

REMARKABLE AND ONCE YOU GET

THE ENGAGEMENT, THE THINGS

THAT CAN BE DONE THAT YOU

JUST COULDN'T HAVE DONE

OTHERWISE ARE GREAT.

NANCY?

>> HI, ROCK.

THANKS FOR A VERY

INTERESTING AND THOUGHTFUL

TALK.

I WAS THINKING A LITTLE BIT

ABOUT HOW

CLINICAL TRIALS.

WHAT YOU WERE

AMERICANIZATIONING IN THE

BEGINNING OF YOUR TALK AND

ONE OF THE THINGS YOU DIDN'T

MENTION WAS LIMITING THE

ELIGIBILITY CRITERIA SO THAT

YOU HAVE A DISEASE.

I THINK YOU WILL BENEFIT

FROM THIS TRIAL, THEREFORE,

I CAN RANDOMIZE YOU.

IT'S BEEN DONE VERY LITTLE

IN OUR HISTORY, BUT IT IS

DONE SOMETIMES.

I WONDER WHY THAT

HEPATOCAUGHT ON.

IT'S A REALLY WAY TO

BASICALLY OPEN UP A TRIAL TO

THE POPULATION FOR WHOM IT

IS OF INTEREST.

>> YOU ARE TALKING ABOUT

UNSERPENT PRIM.

YEAH.

-- PRINCIPLE.

THAT WAS THE BASIS FOR AT

CUTE TRIALS THAT WE ALL DID

TOGETHER.

BUT AGAIN, WE HAD THIS

MARKER, THE

ELECTROCARDIOGRAM.

BY THE WAY, TWO ONLY AGREE

90% OF THE TIME SO IT'S NOT

PERFECT.

BUT YOU HAD TO ONE MARKER

THAT WAS A REAL SIGNIFYER OF

A PROBLEM AND THEN IT WAS AT

THAT POINT VERY EASY TO

RANDOMIZED AND TO DO

COMPARATIVE EFFECTIVENESS

WITH MORTALITY AS THE

OUTCOME.

SO I THINK THE COULD YOU

REPEATER CURRENT NOW THAT WE

HAVE TO THINK THROUGH

CAREFULLY IS IF YOU BELIEVE

THAT THERE ARE STRONG LET'S

SAY GENETIC INFLUENCES ON

THE RESPONSE TO A TREATMENT,

THEN THE GUAM IS YOU DO

BETTER BY FOCUSING YOUR

ENROLLMENT INSTEAD OF BROADENING

IT.

YOU ARE MAKING A PHASE AND

YOU KNOW EXACTLY WHAT I

THINK ABOUT IT,, WHICH IS

THAT MORE THAN HALF THE TIME

THE THOUGHT IS WRONG ABOUT A

JETICALLY BASED STUDY AND I

GOT SOME AMMUNITION TODAY.

I READ IN THE PAPER THAT

THERE WAS ANOTHER STUDY

SEQUENCING DIFFERENT PARTS

OF SURMS -- TURPS AND THE

GENETIC DEFECT IS DIFFERENT

DEPENDING OPT PART OF THE

TUMOR YOU TAKE OUT

APPARENTLY.

I HAVEN'T READ THE PAPER SO

I COULD HAVE MISINTERPRETED.

THE SIMPLE THING TO DO IS

USING A SYSTEM OF ELECTRONIC

HEALTH RECORDS AND YOU'D

HAVE RANDOM NOISE WOULD

FILTER OUT BUT YOU'D HAVE A

MUCH STRONGER SIGNAL BECAUSE

YOU'D HAVE ADEQUATE EVENTS

TO BE ABLE TO SAY SOMETHING.

>> I AM PAUL COTES, DIRECTOR

OF THE OFFICE OF DISEASE

PREVENTION AND JUST TO CLOSE

THIS OUT, I WANTED TO THANK

THE FOLKS WHO CO-SPONSORED

THIS WITH US, THE NATIONAL

HEART-LUNG AND BLOOD

INSTITUTE AND THE NATIONAL

INSTITUTE ON AGING AND THE

NATIONAL INSTITUTE ON

ALCOHOL ABUSE AND ALCOHOL I

LIVE.

THESE ARE JIPT EFFORTS THAT

ENCOURAGE CONVERSATION AT

THE NIH ABOUT AREAS WHERE

THERE IS CONTROVERSY.

I HAVE A FEELING THAT

DR. CAILIFF DID EXACTLY WHAT

WE WAPED IN INVITING HIM TO

COME TO THIS AND RESONATED

WITH LOTS OF YOU.

I KNOW YOU PROBABLY HAVE

OTHER OTHER QUESTIONS, BUT

HE'S ON HIS WAY TO ATLANTA

FOR AN IMPORTANT EVENT.

AND I WANT TO WISH HIM WELL

AND ON BEHALF OF EVERYBODY,

I'D LIKE TO THANK YOU AGAIN.

[APPLAUSE]

>> THANKS.