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>>> GOOD AFTERNOON AND WELCOME
TO THE 2014 ROBERT S GORDON
LECTURE IN EPIDEMIOLOGY. I'M
DAVID MURRAY, ASSOCIATE DIRECTOR
FOR PREVENTION.
AND I'M PLEASED TO REPRESENT
DR. COLINS AND INTRODUCE OUR
SPEAKER.
THE ROBERT S GORDON, Jr.
LECTURE IS AWARDED EACH YEAR TO
A SCIENTIST WHO MADE MAJOR
CONTRIBUTIONS TO RESEARCH ON
TRAINING OR TRAINING IN THE
FIELD OF EPIDEMIOLOGY OR CONDUCT
OF CLINICAL TRIALS.
THE AWARD RECIPIENT IS SELECTED
BASED ON THE RECOMMENDATION OF
THE NIH EPIDEMIOLOGY AND
CLINICAL TRIALS INTEREST GROUP.
THIS IS THE 20th YEAR THE
OFFICE OF DISEASE PREVENTION
HAS SPONSORED THE GORDON LECTURE
AWARD.
IF YOU LOOK AT THE BACK OF YOUR
PROGRAM, YOU WILL SEE A LIST OF
VERY PROMINENT SCIENTISTS WHO
HAVE RECEIVED THIS AWARD IN
PREVIOUS YEARS.
THE GORDON LECTURE AWARD
ESTABLISHED IN TRIBUTE TO ROBERT
S GORDON FOR HIS DEDICATION TO
THE FIELD OF EPIDEMIOLOGY AND
DISTINGUISHED SERVICE TO NINETY
FIVE.
OVER THE COURSE OF 30 YEARS --
NINETY FIVE.
HE WAS SPECIAL ASSISTANT TO THE
DIRECTOR AND CHIEF ADVISOR FOR
CLINICAL PRACTICE AND RESEARCH.
DR. GORDON WAS EARLY ORGANIZER
OF EFFORTS TO ADDRESS THE
EMERGING PROBLEM OF *** AND AIDS
AND BECAME A KEY COORDINATOR FOR
AIDS RESEARCH.
FOR THE LAST 10 YEARS OF SERVICE
TO NIH, DR. GORDON MADE
IMPORTANT CONTRIBUTIONS TO
POLICY AND MANAGEMENT ISSUES
REGARDING EPIDEMIOLOGY, CLINICAL
TRIALS AND THE HEALTH EFFECTS OF
ENVIRONMENTAL HAZARDS.
IT'S A PLEASURE FOR ME TO
INTRODUCE THIS YEAR'S GORDON
LECTURE AWARD RECIPIENT.
MOYSES SZKLO.
DR. MOYSES SZKLO RECEIVED HIS
MEDICAL DEGREE FROM THE
UNIVERSITY OF RIO DE JANEIRO IN
1963.
HE OBTAINED MASTERS IN DR. AND
PUBLIC HEALTH DEGREES FROM
JOHN'S HOPKINS UNIVERSITY IN
1972 AND NOON 74.
HE JOINED THE FACULTY OF
ASSISTANT PROFESSOR AT JOHNS
HOPKINS IN 1974 AND SERVED AS A
PROFESSOR IN THE BLOOMBERG
SCHOOL OF PUBLIC HEALTH SINCE
1980.
JOINED APPOINTMENTS IN
CARDIOLOGY AND ONCOLOGY AT THE
JOHN'S HOPKINS SCHOOL OF
MEDICINE.
DR. MOYSES SZKLO HAS BEEN
PRINCIPAL INVESTIGATOR ON TWO OF
THE LARGEST COHORT STUDIES IN
ANOTHER ROW SCLEROSIS.
THE STUDY WHICH IS
ARTHROSCLEROSIS IN COMMUNITIES
AND THE MESA STUDY, MULTIETHNIC
STUDY OF ARTHROSCLEROSIS
CONTINUING TO MAKE MAJOR
CONTRIBUTIONS TO THE RISK
FACTORS OF CARDIOVASCULAR
DISEASE.
DR. MOYSES SZKLO WRITTEN MORE
THAN 200 PEER-REVIEWED PAPERS
AND LOOKING AT PUBMED LAST NIGHT
AND NOTICED THAT HE IS THE ONLY
SKLO WHO COMES UP WHEN YOU
SEARCH UNDER AUTHORS.
HE ALSO IS THE AUTHOR OF A VERY
WELL-KNOWN TEXTBOOK,
EPIDEMIOLOGY BEYOND THE BASICS,
AND THAT BOOK IS NOW IN THE
THIRD EDITION AND I'M PLEASED TO
SAY I HAVE ALL 3 EDITIONS IN MY
OFFICE.
HIS DEDICATION TO TRAINING IS
EVIDENCE HE RECEIVED MANY AWARDS
FOR TEACHING AND EDUCATIONAL
ACTIVITIES, INCLUDING THE
ESTABLISHENCE MEDAL, ABRAHAM
LILLIAN AWARD AND TWO GOLDEN
APPLES BESTOWED BY THE JOHN'S
HOPKINS SCHOOL OF PUBLIC HEALTH
STUDENT ASSEMBLY FOR EXCELLENCE
IN TEACHING.
HE HAS MENTORED DOZENS OF
MASTERS AND DOCTORAL STUDENTS,
INCLUDING MANY INVESTIGATORS
HERE AT NIH.
HIS PRESENTATION TODAY IS TITLED
"EPIDEMIOLOGY, BACK TO
TRANSLATION."
THERE WILL BE TIME FORE REQUESTS
AFTER THE PRESENTATION AND I
WOULD ALSO INVITE EVERYONE WHO
IS HERE THIS AFTERNOON TO JOIN
ME AT A RECEPTION FOR HIM IN THE
NIH LIBRARY JUST ACROSS THE HALL
TO MY LEFT.
NOW PLEASE JOIN ME IN WELCOMING
THIS YEAR'S ROBERT S
GORDON, Jr. LECTURE AWARD
RECIPIENT, DR. MOYSES SZKLO.
[ APPLAUSE ]
>> THIS IS A REAL HONOR.
I'M VERY HONORED TO BE THIS
YEAR'S ROBERT S GORDON LECTURER
AND I'D LIKE TO THANK YOU FOR
CHOOSING ME AND DR. MURRAY AND I
ALSO WANT TO THANK FOR BEING AN
IMPECCABLE HOSTESS AND I ALWAYS
HAVE BEEN IN AWE OF DR. GORDON'S
ACCOMPLISHMENTS SO IT'S A
SPECIAL HONOR.
NOW, TALK ABOUT TRANSLATIONAL
EPIDEMIOLOGY, OF COURSE NOT NEW.
EPIDEMIOLOGY AS YOU KNOW WAS
BORNE OUT OF THE NEED TO PROVIDE
RESEARCH FINDINGS AND EVALUATION
TOOLS FOR THE PUBLIC HEALTH
PRACTITIONER AND FROM THE 30
DAYS, IT WAS CONSISTENT WITH
CONTENTION.
IN THAT KNOWLEDGE, IT SHOULD BE
APPLIED TO PLANNING AND
IMPLEMENTATION OF PUBLIC HEALTH
ACTION.
NOW YOU KNOW, AN IMPORTANT
LANDMARK WAS STUDIES ON CHOLERA
IN LONDON IN THE APPLICATION OF
THE RESULTS OF THIS STUDIES TO
CONTROL CHOLERA.
WHAT IS EXTRAORDINARY ABOUT
SNOW, IS THAT ON THE BASIS OF
HIS EPIDEMIOLOGICAL OBSERVATIONS
AND MANY YEARS BEFORE THE
MICROBIOLOGY ERA, HE CONCLUDED
THAT THE AGENT RESPONSIBLE FOR
CHOLERA WAS A LIVE ORGANISM THAT
COULD MULTIPLY.
ON THE OTHER HAND AND
PARENTHETICALLY, YOU KNOW ABOUT
THE BROAD STREET PUMP.
AND HE REMOVED THE PUMP AND
THEORETICALLY, HE WOULD HAVE
STOPPED THE CHOLERA EPIDEMIC.
BUT WHAT SOME OF YOU MAY NOT
KNOW IS THAT WHEN THE HANDLE WAS
REMOVED, THE EPIDEMIC WAS
ALREADY ON THE WAY.
PROMPTING THE DEFINITION OF AN
EPIDEMIOLOGY I FELT AS SOMEONE
WHO CLOSE TO GLORY IN A
DESCENDING PORTION OF THE
ACADEMIC CURVE.
NOW OBVIOUSLY THIS DEFINITION
DOESN'T APPLY TO FROST WHOSE KEY
CONTRIBUTIONS BASICALLY CHANGED
THE PARADIGM OF CHOLERA
TRANSMISSION.
NOW IT IS INTERESTING THAT UNTIL
ABOUT 30-40 YEARS AGO, MOST OF
THE EPIDEMIOLOGIST IN THE
ACADEMIA HAD SIGNIFICANT PUBLIC
HEALTH BACKGROUND AND CONSIDERED
THEIR RESPONSE ABILITY TO APPLY
RESULTS OF EPIDEMIOLOGICAL
RESEARCH TO THE SOLUTION OF
PRACTICAL PUBLIC HEALTH
PROBLEMS.
NOW TAKE FOR EXAMPLE, MORTON
LEVINE.
ONE OF THE FIRST INVESTIGATION
TO REPORT IN THE ASSOCIATION
BETWEEN LUNG CANCER AND SPENT
THE LAST YEAR'S OF HIS
PROFESSIONAL LIFE AS A PROFESSOR
AT JOHN'S HOPKINS.
SO HIS COUNTEDBUTIONS TO
ACADEMIC EPIDEMIOLOGY WERE
CONSIDERABLE.
YET HE WAS SURPRISED AT BEING
CHOSEN AS THE RECIPIENT OF THE
FROST AWARD FOR THE AMERICAN
PUBLIC HEALTH ASSOCIATION FOR
EXCELLENCE IN EPIDEMIOLOGY AS HE
SAW HIMSELF PRIMARILY AS A
PUBLIC HEALTH WORKER, NOT AS AN
EPIDEMIOLOGIST.
IN THIS SELF-IMAGE ALSO EXPLAINS
WHY HE BELIEVED HIS MOST
IMPORTANT CONTRIBUTION TO PUBLIC
HEALTH HAD BEEN TO FACILITATE
THE POLIO VACCINE TRIALS IN
NEW YORK CITY AS A HEALTH
OFFICER AND TO MAKE SURE THAT A
RANDOM ALLOCATION SCHEDULE WAS
USED.
HE WAS THE FIRST TO DEVELOP THE
CONCEPT AND FORMULA FOR THE
UNADJUSTED POPULATION
ATTRIBUTABLE RISK, WHICH HE DID
TO HELP HIM IN THE PLANNING OF
PREVENTION STRATEGIES WHICH
DEVELOPED RISK ALONE COULD NOT
DO.
NOW LET'S TURN TO SPECIFICALLY
TO TRANSLATIONAL RESEARCH.
THERE ARE SEVERAL DEFINITIONS OF
TRANSLATIONAL RESEARCH.
FOR EXAMPLE, THE CLINICAL AND
TRANSLATIONAL SCIENCE INSTITUTES
DEFINITION FOR THE NATIONAL
CANCER INSTITUTE IS THAT
TRANSLATIONAL RESEARCH IS A TYPE
OF RESEARCH THAT TRANSFORMS
SCIENTIFIC FINDINGS FROM
LABORATORY, CLINICAL OR
POPULATION STUDIES INTO CLINICAL
APPLICATIONS TO REDUCE
INCIDENTS, MORBIDITY AND
MORTALITY.
NOW THE INSTITUTE OF MEDICINE
DEFINES TWO TRANSLATIONAL
BLOCKS.
BLOCK 1 IS THE TRANSFER OF NEW
UNDERSTANDINGS OF DISEASE
MECHANISMS GAINED IN THE
LABORATORY INTO THE DEVELOPMENT
OF NEW METHODS FOR DIAGNOSIS,
THERAPY AND PREVENTION AND THEIR
FIRST TESTING IN HUMANS.
AND BLOCK 2, TRANSLATION OF
RESULTS FROM CLINICAL STUDIES
INTO EVERY DAY CLINICAL PRACTICE
AND HEALTH DECISION-MAKING.
NOW MORE SPECIFIC
EPIDEMIOLOGICAL DEFINITION WHICH
CONSIDERS THE FULL SCOPE OF
EPIDEMIOLOGY MIGHT BE ALONG THE
FOLLOWING LINES: EFFECTIVE
TRANSFER OF NEW KNOWLEDGE
RESULTING FROM EPIDEMIOLOGICAL
STUDIES, INCLUDING TRIALS, INTO
THE PLANNING OF POPULATION-WIDE
AND INDIVIDUAL-LEVEL DISEASE
CONTROL PROGRAMS AND POLICIES.
NOW TRANSLATIONAL EPIDEMIOLOGY
AND TRANSLATIONAL SCIENCE IN
GENERAL ARE CLOSELY RELATED BUT
ALSO SOMEWHAT DISTINCT FROM
IMPLEMENTATION SCIENCE, WHICH
HAS BEEN DEFINED BY THE
INSTITUTE OF MEDICINE AS SEEKING
TO UNDERSTAND THE BEHAVIOR OF
HEALTH CARE PROFESSIONALS AND
OTHER STAKEHOLDERS AS A KEY
VARIABLE IN SUSTAINABLE UPTAKE
ADOPTION AND IMPLEMENTATION OF
EVIDENCE-BASED INTERVENTIONS.
DOES IMPLEMENTATION SCIENCE
SEEMS TO BE PRIMARILY FOCUSED ON
THE LOGISTICS OF IMPLEMENTATION
TO THE EXTENT IT SEEKS TO
PROMOTE INTEGRATE EVIDENCE-BASED
INTERVENTION INTO HEALTH CARE
PRACTICE.
NOW IN TERMS OF HEALTH POLICY, I
THINK IT'S VERY INTERESTING TO
CONSIDER THE PROPOSAL OF A GROUP
SUMMARIZING ALL STAGES IN
DISEASE CONTROL WHICH INCLUDE
ASSESSING THE BURDEN OF ILLNESS,
STUDYING THE ETIOLOGY OF DISEASE
AND THE RISK FACTOR BURDEN,
DETERMINING EFFICACY AND THEN
COMMUNITY EFFECTIVENESS AND
EVALUATING COST-EFFECTIVENESS,
IMPLEMENTING AND MONITORING
PROGRAM AND POLICY AND FINALLY
REASSESSING THE BURDEN OF
ILLNESS AND/OR RISK FACTORS.
SO EPIDEMIOLOGY IS REPRESENTED
IN VIRTUALLY ALL THESE PHASES.
WE COULD -- WITH THE POSSIBLE
EXCEPTION OF COST-EFFECTIVENESS
IN THE IMPLEMENTATION OF THE
PROGRAM.
WHILE COMMUNITY EFFECTIVENESS IS
THE, IN MY OPINION, THE MAIN
FOCUS OF TRANSLATIONAL
EPIDEMIOLOGY, COST EFFECTIVENESS
IS THE MAIN TARGET OF HEALTH
TECHNOLOGY ASSESSMENT UNITS.
AND AS ALL KNOW, EPIDEMIOLOGY
HAS MADE MAJOR CONTRIBUTIONS TO
PUBLIC HEALTH OVER THE YEARS,
INCLUDING THE SMOKING PREVENTION
STRATEGIES, RADIATION AND AIR
POLLUTION STANDARDS AND OTHERS.
SO I'LL TURN TO THE
TRANSLATIONAL PROCESS ITSELF.
NOW THIS IS THE CLASSICAL
DEFINITION OF EPIDEMIOLOGY.
THE STUDY OF DISTRIBUTION AND
DETERMINEENANCE OF
HEALTH-RELATED STATES OR EVENTS
IN SPECIFIED POPULATIONS AND THE
APPLICATION OF THIS STUDY TO
CONTROL HEALTH PROBLEMS.
THUS THE DEFINITION HAS TWO
COMPONENTS.
IT CHALLENGES REALLY TO
TRANSLATE FROM THE FIRST TO THE
SECOND COMPONENT, WHICH IS
REALLY NOT A STRAIGHTFORWARD
PROCESS.
NOW YOU ALL KNOW ABOUT THIS
CARTOON.
IT'S VERY WELL-KNOWN.
SO IS THERE A STEP IN THE
PROCESS THAT IS NOT TOTALLY
SCIENTIFIC.
THE NATURAL HISTORY OF
TRANSLATIONAL PROCESS STARTS
WITH THE ACQUISITION OF
EVIDENCE, OF COURSE, FROM
EPIDEMIOLOGICAL STUDIES.
I'M TALKING ABOUT SPECIFICALLY
TRANSLATIONAL EPIDEMIOLOGY.
THE NEXT STEP SHOULD BE IDEALLY
SYSTEMATIC REVIEWS, ALTHOUGH
SOMETIMES POLICYMAKERS HAVE TO
RELY ON RESULTS OF A SINGLE
STUDY, PARTICULARLY IF THESE
STUDIES ARE RANDOMIZED TRIAL OF
GOOD QUALITY.
THE NEXT STEP IS EVALUATION OF
LEVELS OF EVIDENCE AND SELECTION
OF PROGMMATIC OR POLICY OPTIONS
RESULTING FROM DECISION
ANALYSIS.
I WOULD PROPOSE IN THIS PHASE IT
IS CLEARLY IN THE REALM OF
TRANSLATIONAL EPIDEMIOLOGY.
ADDITIONAL STEPS REQUIRE
EXPERTISE OUTSIDE OF
EPIDEMIOLOGY AND INCLUDE
ESTIMATION OF COST EFFECTIVENESS
WITH SENSITIVITY ANALYSIS,
RECOMMENDATIONS AND FINALLY,
EVIDENCE-BASED POLICIES IN WHICH
THERE IS OFTEN ATTENTION BETWEEN
EVIDENCE OBSTACLES SUCH AS THOSE
RELATED TO RESOURCES, ETHICAL
PROBLEMS, POLITICS, ET CETERA.
NOW, LET ME GIVE YOU A FURTHER
IMPLEMENTATION.
WHAT I'M GOING TO DO IS USE
CONCEPTS BY THE TASK FORCE AND
CANADA'S PERIODIC HEALTH
EXAMINATION.
I CAN SEE OTHER TYPES OF MODELS
TO DESCRIBE THE ENTER ACTION
BETWEEN KNOWLEDGE, TRANSLATION,
AND IMPLEMENTATION.
NOW AS I HAVE ALREADY MENTIONED,
IN TRANSLATIONAL PROCESS, STARTS
WITH EVALUATION OF THE LEVELS OF
EVIDENCE.
AND THEY ARE ADDRESSING THE
ISSUE OF WHETHER THE
INTERVENTION PROGRAM OR POLICY
DOES MORE GOOD THAN HARM.
SO LEVEL 1 IS DEFINED BY ONE
WELL DESIGNED CLINICAL TRIAL.
NUMBER 2 REFERS TO DESIGN
OBSERVATIONAL STUDIES.
LEVEL 22 IS BASED ON DRAMATIC
RESULTS IN UNCONTROLLED
EXPERIMENTS SUGGESTING THAT
INTERVENTION DOES MORE GOOD THAN
HARM.
SO THIS IS SO-CALLED NATURAL
EXPERIMENTS.
THAT'S THE DRIVER THAT
EPIDEMIOLOGISTS USE.
FOR EXAMPLE, THOSE THAT HAVE
SHOWN A SHARP DECLINE IN THE
INCIDENTS OF TB MENINGITIS,
AFTER THE INTRODUCTION OF
SEPTEMBER MICE IN, WILL DECLINE
IN DIABETES MORTALITY FOLLOWING
THE INTRODUCTION OF INSULIN.
A RECENT EXAMPLE IS THE SHARP
DECREASE IN CALORIC INTAKE
DURING THE CRISIS RESULTING FROM
THE ECONOMIC BLOCKADE IN CUBA
LASTING FROM 1989-2000 WITH A
SHIFT TO THE LEFT OF THE BODY
MASS INDEX DISTRIBUTION IN
CORRESPONDING DECREASING
PREVALENCE.
NOW IN THIS SLIDE, THE MORE
DARKER SHADED AREAS COINCIDE
WITH THE PEOPLE WITH THE
ECONOMIC CRISIS WHICH OCCUR FROM
1991-1995.
NOTE THE STRIKING DECLINE IN
MORTALITY FROM CORONARY HEART
DISEASE IN CUBA THAT OCCURRED AT
THE BEGINNING OF THE WORST PHASE
OF THE BLOCKADE.
SO THIS DATA SUGGESTS THAT THE
CALORIC RESTRICTIONS ARE A KEY
FACTOR IN THE PREVENTION OF
OBESITY IN THESE CONSEQUENCES.
IN THE POPULATION-WIDE MEASURES,
UNFORTUNATELY THIS CASE UNDER
UNHAPPY CIRCUMSTANCES OF COURSE
ARE LIKELY TO BE AFFECTED.
ADDITIONALLY, VALID, THIS DATA
SURPRISINGLY SUGGESTS THAT THE
OBESITY ON CORONARY HEART
DISEASE MORTALITY SEEMS TO BE
CHARACTERIZED BY A SHORT
INCUBATION PERIOD OF
APPROXIMATELY 1-2 YEARS, WHICH
IMPLIES MEDIATORS OF THIS
RELATIONSHIP SUCH AS
INFLAMMATORY MARKERS MAY HAVE A
PRECIPITATING EFFECT.
THERE WAS ALSO A SHARP DECLINE
IN DIABETES MORTALITY.
BUT IT SEEMED TO HAVE A LONGER
LATENCY THAN THE LATENCY OF
CORONARY MORTALITY ASSOCIATED.
LET'S GO BACK TO THE LEVELS OF
EVIDENCE AND IF I'MY LEVEL ROMAN
3 REFERS TO THE OPINION OF THE
RESPECTED PEOPLE IN THE FIELD
CONVINCED OF THE VALUE OF THE
INTERVENTION BASED FOR EXAMPLE
ON K SERIES OR CLINICAL
EXPERIENCE.
SO HOW IS ACTUAL TRANSLATION
DONE BASED ON THESE LEVELS OF
EVIDENCE?
I THINK THAT TRANSLATION
EPIDEMIOLOGY, EVEN WHEN BASED ON
EVIDENCE, IS REALLY NOT AN EXACT
SCIENCE.
REMINDING ME OF THE REMARK THAT,
DEATH IS A FACT.
ALL ELSE IS INFERENCE.
HE MEANT THAT ALTHOUGH EVERYONE
DIES, THE INFORMATION IS
IMPERFECT AND THERE ARE TRAPS IN
THESE INTERPRETATION IN
APPLICATION.
SO, LET'S MOVE ALONG AND TALK
ABOUT RECOMMENDATIONS FOR
TRANSLATIONAL EVIDENCE INTO
PROGRAMS OR POLICIES.
AND AGAIN, THIS IS JUST ONE OF
THE WAYS TO DO IT.
IT'S NOT THE ONLY ONE.
GRADES A&B IN TRANSLATION
EXPRESS HIGH CERTAINTY THAT IN
THAT BENEFIT, SUBSTANTIAL,
MODERATE OR MODERATE TO
SUBSTANTIAL.
AND SO THE RECOMMENDATION WOULD
BE TO DESIGN AND OFFER THE
INTERVENTION FOR A PROGRAM.
GRADE C IS IT IS MODERATE OR
HIGH CERTAINTY THE NET BENEFIT
IS SMALL.
IT JUSTIFIES THE RECOMMENDATION
THAT THE INTERVENTION SHOULD BE
AVAILABLE TO SINGLE INDIVIDUALS,
CONDITIONAL UPON OTHER
CONSIDERATIONS, FOR EXAMPLE,
WHEN OFFERING A PSA TEST,
PROSSTATE SPECIFIC ANTIGEN TEST,
MAKING SURE THE INDIVIDUAL
UNDERSTANDS HIS POTENTIAL
BENEFITS AND RISKS.
GRADE D REFERS TO MODERATE OR
HIGH CERTAINTY THAT THERE IS NO
NET BENEFIT OR THAT THE HARMS
OUTWEIGH THE BENEFITS IN WHICH
CASE THE INTERVENTION SHOULD BE
DISCOURAGED.
AND GRADE I IS THE CURRENT
EVIDENCE FOR THE DECISION MAKING
IS MISSING, POOR OR
INCONSISTENT.
AND DOES THE RECOMMENDATION BE
THAT THE IF THE INTERVENTION IS
OFFERED, INDIVIDUALS SHOULD
THROUGHLY UNDERSTAND THE
UNCERTAINTY ABOUT THE BALANCE OF
BENEFITS AND HARMS.
NOW, WHAT I WOULD LIKE TO DO
FROM NOW ON IS TO TALK ABOUT
SOME CONCEPTS RELEVANT TO THE
TRANSLATIONAL EPIDEMIOLOGY.
I'M NOT GOING TO DISCUSS
SPECIFIC STRATEGIES THAT ARE
IMPORTANT FOR TRANSLATION SUCH
AS COMPARATIVE EFFECTIVENESS, OR
TRANSLATIONS IN THIS NATURE.
INSTEAD, I WOULD LIKE TO BRIEFLY
DISCUSS SOME SPECIFIC
EPIDEMIOLOGICAL CONCEPTS THAT
ARE RELEVANT IN KNOWLEDGE
TRANSLATION.
I HOPE I CAN PERSUADE YOU TO
AGREE THAT SOME OF THE CONCEPTS
NEEDED FOR TRANSLATION COUNTER
WHAT MOST STUDENTS HAVE BEEN
TAUGHT THESE DAYS IN THE
ACADEMIA.
THIS INCLUDES RATHER CONFOUNDING
SHOULD ALWAYS BE REGARDED AS A
BIAS.
THE RELIANCE ON HOMEGENEITY OVER
RESULTS OF CROSS STUDIES ON
EFFECTIVENESS, AND ISSUES
RELATED TO HETEROGENEITY OR
FINDINGS.
SO THE NATURE OF THE FIRST
ISSUE, THAT I'D LIKE TO DISCUSS
IS SOMEWHAT SEMANTICS, THAT IS
WHETHER CONFOUNDING SHOULD BE
ALWAYS CONSIDERED A BIAS AND THE
IMPLICATIONS OF CREATING
CONFOUNDING WITH BIAS.
NOW, IN SOME MODERN TAX GROUPS
OF EPIDEMIOLOGY AND
BIOSTATISTICS, BIAS IS
CLASSIFIED AS DUE OR NOT DUE TO
CONFOUNDING.
THE PROBLEM THAT TRANSLATION
EPIDEMIOLOGY FACES IS THAT
POLICY OFTEN HAS TO BE BASED ON
OBSERVATIONAL EPIDEMIOLOGY AND
THUS CONFOUNDING IS ALWAYS AN
IMPORTANT CONCERN.
SO WE ARE TALKING ABOUT STUDIES
LIKE CASE CONTROL STUDIES AND
COHORT STUDIES.
WITH REGARD TO THE USE OF THE
OBSERVATIONAL DOMAIN OF
EPIDEMIOLOGY, EPIDEMIOLOGY IS OF
COURSE AN EXCELLENT COMPANY.
THERE ARE LOTS OF FUELS THAT ARE
OBSERVATIONAL IN NATURE
INCLUDING ASTRO FIDSICS, GEOLOGY
AND OTHERS.
-- ASTRO PHYSICS.
THE PROBLEM IS NOTWITHSTANDING
RECENT ADVANCES TO HANDLE
CONFOUNDING SUCH AS INSTRUMENTAL
VARIABLES, RANDOMIZATION,
PROPENSITY, ET CETERA, GIVEN THE
POSSIBILITY OFY RESIDUAL
CONFOUNDING, THE INFERENCE FROM
OBSERVATIONAL DATA HAS TO BE
MADE WITH CAUTION.
SO THE QUESTION IS, THESE ARE
CONFOUNDING ASSOCIATION USEFUL?
OR IS IT A BIAS WE MUST KILL
OFF?
I MEAN USEFUL FOR IMPLEMENTING
PUBLIC HEALTH ACTION.
THIS SLIDE SUMMARIZES
SCHEMATICALLY WHAT I WOULD CALL
THE FOR HISTORY OF A STUDY.
IT STARTS WITH THE
IDENTIFICATION OF A STUDY BASE
AND TARGET POPULATION AND THEN
PROCEEDS TO SELECT A STUDY
PARTICIPANTS AND COLLECT DATA
WHICH AFTER BEING ANALYZED ARE
REPORTED AS A STUDY FINDINGS.
SO UNLESS OR UNLIKE SELECTION OF
BIAS, RESULTING FROM BIAS
SAMPLING WITH WHICH IS OFTEN
CONFUSED, CONFOUNDING IS FOUND
IN NATURE, MEANING AT THE
POPULATION LEVEL.
SO THE QUESTION IS, IS THIS
DIFFERENT?
AND I WILL TELL YOU THAT I THINK
IT IS TERRIBLY IMPORTANT FOR
TRANSLATION EPIDEMIOLOGY.
I'LL GIVE AN EXAMPLE.
LET'S ASSUME THAT I'M INTERESTED
IN THE RELATIONSHIP BETWEEN
AFRICAN AMERICANETH NIECITY AND
HYPERTENSION?
LET'S ASSUME THAT THE
RELATIONSHIP IS ENTIRELY
EXPLAINED BY CONFOUNDING BY RISK
FACTORS SUCH AS DIET RICH IN
SALT, OBESITY, LOW LEVELS OF
PHYSICAL ACTIVITY AND
NEIGHBORHOOD-RELATED STRESS AND
JOB STRAIN IT IS SOON-TO-BE
CONFOUNDED NOT CAUSAL.
AFRICAN AMERICANS HAVE A HIGHER
RISK OF HYPERTENSION.
I THINK IT IS QUITE OBVIOUS THAT
AFRICAN AMERICAN ETHNICITY IS A
HIGH RISK GROUP.
AND THAT THIS KNOWLEDGE CAN BE
QUITE USEFUL IN SCREENING FOR
HYPERTENSION IN THIS SECOND
GROUP.
AND ALSO FOR PROMOTING
SAYSSATIONAL PRIMORDIAL
PREVENTION AND FOCUS ON RISK
FACTORS.
YES, IF YOU WANT TO THE INFER A
CAUSAL RELATIONSHIP.
SO IT IS IMPORTANT TO
DISTINGUISH BETWEEN EAT LOGICAL
CONFOUNDING AND PUBLIC HEALTH
CONFOUNDING AND A LOT OF
EXPRESSION WAS SUGGESTED BY
DONNA SPIEGEL MAN FROM HARVARD
SCHOOL OF PUBLIC HEALTH.
AND ALSO I SHOULD POINT OUT THAT
THE USEFULNESS OF A CONFOUNDING
ASSOCIATION FOR PUBLIC HEALTH
DEPENDS ON THE PROBLEMS OF THE
CONFOUNDER OR THE CONFOUNDERS IN
THE TARGET POPULATION.
EXCUSE ME.
I DON'T THINK I CAN OFFER YOU
WATER.
SO, NOW I'D LIKE TO TURN TO OUR
TOPIC THAT PERHAPS MORE THAN ANY
OTHER UNDERSCORES THE GAP
BETWEEN ACADEMIC AND TRANSLATION
EPIDEMIOLOGY.
AND THAT IS THE CHOICE OF THE
MODEL WE USE.
REGRETTABLY, CONSIDERING
TRANSLATIONAL EPIDEMIOLOGICAL
KNOWLEDGE, THE ESTIMATION OF THE
MEASURE OF ASSOCIATION OR
EVALUATION OF INTERACTION IS
USUALLY A FUNCTIONAL STATISTICAL
MODEL OR SKILL TO BE USED RATHER
THAN DICTATED BY THE NEED TO USE
THE KNOWLEDGE IN PLANNING AND
IMPLEMENTING PUBLIC HEALTH
POLICIES AND PROGRAMS.
THIS ISSUE IS GRASPING BY
CONSIDERING THE PHENOMENAL
INTERACTION.
SO WHEN IT IS QUALITATIVE SUCH
AS IN THE CASE HERE, IT IS
OBVIOUSLY PRESENT IN BOTH THE
ADDITIVE AND MULTIPLICATIVE
SCALES.
ON THE OTHER HAND, CAUTION IS
NEEDED WHEN ASSESSING THE
PRESENCE OF QUANTITATIVE
INTERACTIONS.
AND I HAVE A DRAMATIC EXAMPLE
HERE THAT COMES FROM A SECONDARY
PREVENTION STUDY.
AND THE AUTHOR STRATIFIED THE
DATA ACCORDING TO DIABETES AND
EXAMINING THE RISK OF A
SUBSEQUENT INFARCTION FOR THOSE
ALREADY HAD A PREVIOUS
INFARCTION COMPARED TO THOSE WHO
NEVER HAD A PREVIOUS INFARCTION.
SO THE INCIDENTS FOR THOSE WHO
ALREADY HAD A PREVIOUS
INFARCTION IS THE INCIDENTS OF
RECURRENT INFARCTION.
AS CAN SEE IN THIS SLIDE, THE
RELATIVE RISK WAS FOUND TO BE
GREATER WHEN A HISTORY OF
DIABETES WAS AB 70.
THEN, WHEN IT WAS -- ABSENT.
THEN WHEN IT WAS PRESENT, THERE
WAS A NEGATIVE INTERACTION,
WHICH IS COMPLETELY COUNTER
INTUITIVE.
SO, DOES THIS FINDING MEAN THAT
IF RESOURCES ARE LIMITED AND ONE
WISHES TO PREVENT A CURRENT
INFARCTION, IT WOULD BE
PREFERRABLE TO FOCUS ON THOSE
WITHOUT DIABETES?
NOW, I MUST SAY PARENTHETICALLY
THIS IS PURELY THEORETICAL
BECAUSE WITH THE CURRENT
INFARCTION SHOULD BE PREVENTED
REGARDLESS OF MODIFICATION BUT
THE EXAMPLE SERVES TO IMSTRAIGHT
MY POINT.
NOW INSPECTION OF ABSOLUTE
DIFFERENCES GIVES US AN OPPOSITE
PICTURE.
THE ABSOLUTE DIFFERENCE IN
INCIDENCE WAS GREATER THAN THOSE
WITH DIABETES THAN IN THOSE
WITHOUT DIABETES.
SO THERE IS A POSITIVE
INTERACTION.
SO, IN OTHER WORDS, IN ASSUMING
HOMOGENEOUS DISTRIBUTION OF THIS
FACTOR, THE POPULATION BY
PREVENTING A SUBSEQUENT
INFARCTION IN THOSE WITH
DIABETES A GREATER NUMBER OF
CASES OF RECURRENT INFARCTION
COULD BE PREVENTED.
SO THIS FINDING IN THIS EXAMPLE
CAN OF COURSE BE EXPLAINED BY
THE FACT THAT THE RELATIVE RISK
IS IN THE EXAMPLE AND IS
AFFECTED BY THE HIGH BASELINE
INCIDENTS OF THE REFERENCE
CATEGORY IN THOSE WITH DIABETES
AND THIS IS ALSO LIKELY TO BE A
TRUE MODIFIER THAT IS POTENT
RISK FACTORS.
NOW, AS TRANSLATION EPIDEMIOLOGY
FOCUSED ON ABSOLUTE NUMBER OF
CASES AND DEATHS THAT CAN BE
PREVENTED, THIS EXAMPLE
HIGHLIGHTS THE FACT THAT FOR
TRANSLATION TO PUBLIC HEALTH AND
ALSO CLINICAL PRACTICE, THE
ADDITIVE MODEL SHOULD BE THE
PREFERRED ONE, NOT THE
MULTIPLICATIVE MODEL.
AND VERY INTERESTING, SOME
PEOPLE DON'T REALIZE EACH IF YOU
USE A MULTIPLICATIVE MODEL LIKE
LOGISTICS, YOU CAN STILL
EVALUATE THAT INTERACTION IN THE
CONTEXT OF THAT MULTIPLICATIVE
MODEL.
AND KEN ROBBING MAN COINED THE
TERM, PUBLIC HEALTH INTERACTION
TO EXPRESS POSITIVE ADDITIVE
INTERACTIONS.
NOW LET ME GO BACK ONCE MORE TO
THE LEVELS OF EVIDENCE.
SO THE GUIDELINES IN THIS SLIDE
ARE MORE DETAILED THAN THOSE
THAT I SHOWED YOU BEFORE.
AND THE RAISING LEVEL SHOWN HERE
GO FROM BEST TO WORSE.
OF COURSE BEST IS A SYSTEMATIC
REVIEW OF RANDOMIZED TRIALS AND
WORSE IS THE OPINION OF EXPERT,
THAT IS NOT EVIDENCE-BASED.
ALTHOUGH THESE GUIDELINES CAN BE
USED FOR ANY OUTCOME,
TRANSLATIONAL EPIDEMIOLOGY IS
PARTICULARLY CONCERNED WITH
STUDIES OF EFFECTIVENESS.
NOW, WHAT IS INTERESTING IS THAT
FOR EACH STUDY OR EACH TYPE OF
STUDY DESIGN, RANDOMIZED TRIAL,
COHORT STUDIES, CASE CONTROL
STUDIES, THE HIGHEST LEVEL OF
EVIDENCE COMES FROM A SYSTEMATIC
REVIEW OF HOMEGENEITY.
SO, HOMEGENEITY ISY SUPPORTED.
EXCUSE ME, GENERALLY USED IN
SUPPORT OF EFFECTIVENESS AND
HETEROGENEITY IS AGAINST
EFFECTIVENESS.
BUT THESE CONCLUSIONS MAY BE
UNWARRANTED.
I'D LIKE TO TALK ABOUT PROBLEMS
WITH HOMEGENEITY AND
HETEROGENEITY.
HOMEGENEITY MAY BE THE MOST
COMMONLY USED OF ALL CRITERIA TO
INFER CAUSALITY OR
EFFECTIVENESS.
NOW STARTING WITH HOMEGENEITY.
AS YOU KNOW THIS PUBLICATION
BIAS, I USE THE TERM,
PSEUDOHOMEGENEITY WHEN
CONSISTENT PUBLISH RESULTS
ACROSS STUDIES IS A CONSEQUENCE
OF PUBLICATION BIAS SO SOME
QUESTIONS PERTAINING TO
PUBLICATION BIAS ARE THESE RUM
OF EDITORIAL POLICIES --
RESULT -- ARE ALTOGETHERRORS
AFRAID OF REJECTION OF NEGATIVE
RESULTED?
THERE IS SOME DATA SHOWING WHEN
THE RESULTS ARE NOT WHAT THE
INVESTIGATOR EXPECTS, HE OR SHE
DOES NOT SEND THE ARTICLE FOR
PUBLICATION.
THEY DON'T PUBLISH THE REPORT.
SO REJECTION EXPERIENCE CAN BE
QUITE TRAUMATIC SUCH AS ONE
EXPERIENCED BY SNOOPY.
SO SNOOPY SENT A PAPER TO THE
AMERICAN JOURNAL OF EPIDEMIOLOGY
AND I WROTE HIM THIS FOLLOWING
LETTER.
D. AUTHOR, THANK YOU FOR
SUBMITTING YOUR ARTICLE TO OUR
MAGAZINE.
TO SAVE TIME, WE ARE ENCLOSING
TWO REJECTION SLIPS AND I FEEL
LIKE DOING THAT OFTEN.
ONE FOR THIS ARTICLE AND ONE FOR
THE NEXT ONE YOU SEND US.
[ LAUGHS ]
BUT ACTUALLY, IT HAS BEEN SHOWN
THAT THE MAIN REASON WHY PAPERS
BASED ON COMPLETED STUDIES AND
NOT PUBLISHED, IS THAT AUTHORS
DON'T SUBMIT THEM.
I FOUND A FEW RELATIVELY OLD
STUDIES BUT I COULDN'T FIND ANY
RECENT ONES ADDRESSING THE
TERMENANCE OF PUBLICATION
RELATED TO AUTHORS AND THIS IS
VERY TYPICAL RESULT.
STUDIES THAT ARE STATISTICALLY
SIGNIFICANT HAVE NOD TWO TIMES
HIGHER OF PUBLICATION WHEREAS
ALSO EXPERIMENTAL STUDIES ARE
LEVELS LIKELY TO BE PUBLISHED
ONCE THE STUDY IS DONE.
I'M TALKING ABOUT STUDIES THAT
HAVE BEEN DONE, COMPLETED AND
SOMETIMES HAS GONE BY, WHICH
REALLY OTHERWISE THE LACK OF
PUBLICATION MEANS JUST THE
AUTHORS -- DON'T HAVE THE TIME
TO WRITE THE PAPER.
SO, TYPICAL RESULT CAN BE SHOWN
IN THIS SLIDE.
THE OTHER DETERMINANT, WHICH IS
ALSO HAVE BEEN SHOWN OVER AND
OVER AND OVER AGAIN, THE TYPE OF
SPONSORSHIP, PRIVATE OR
GOVERNMENTAL, AND THIS IS JUST
AN EXAMPLE OF ANALYSIS OF 321
RANDOMIZED CHEMICAL TRIALS AND
THE ODDS OF PUBLICATION ON PAPER
IS ENDORSING THE EXPERIMENTAL
ARM OR MORE THAN 3 TIMES HIGHER
WHEN THE SPONSOR WAS FOR PROFIT
THAN WHEN IT WAS NOT.
AND THE ODDS RATIO FOR
SIGNIFICANT RESULTS WAS CLOSE TO
20.
THERE HAVE BEEN MANY SYSTEMATIC
REVIEWS SHOWING EXACTLY THE SAME
FINDINGS EVEN THOUGH THE ODDS
RATIO VARIES A LITTLE BIT FROM
STUDY TO STUDY OR FROM
SYSTEMATIC REVIEW TO SYSTEMATIC
REVIEW.
SO THIS IS WHAT BRAD HILL SAID
ABOUT NEGATIVE RESULTS.
THEY MAY BE DULL BUT OFTEN IT IS
NOT LESS IMPORTANT THAN THE
POSITIVE AND IN VIEW OF THAT,
MUST BE SURE NEWLY-ESTABLISHED
BY ADEQUATE PUBLICATION OF THE
EVIDENCE.
NOW THE -- EVAACT
THAT RELEVANT PAPERS HAVE BEEN
IDENTIFIED.
NOW, A MORE COMPLEX ISSUE, WHICH
HAS MORE DERMENANCE AND RELATES
TO HETEROGENEITY OF RESULTS.
AND OF COURSE, ONE OF THE MAIN
REASONS WHY RESULTS ARE
HETEROGENEITY IS THE ASSOCIATION
IS NOT THERE.
SO YOU SEEN EACH STUDY DEPARTING
FROM THE NEW HYPOTHESES JUST AS
A RANDOM VARIABILITY AROUND THE
NEW HYPOTHESES.
BUT THERE ARE OTHER REASONS FOR
HETEROGENEITY EACH IF THE
ASSOCIATION IS PRESENT.
SUCH AS FOR EXAMPLE, DIFFERENCES
IN STUDY DESIGN, PROCEDURES AND
QUALITY.
AND QUALITY CAN BE MARKEDLY
VARIABLE ACROSS STUDIES.
THIS IS SYSTEMATIC REVIEW OF 83
STUDIES OF THE RELATIONSHIP OF C
REACTIVE PROTEIN TO CORONARY
HEART DISEASE.
YOU CAN SEE THAT ONLY ABOUT 45%
OF ALL STUDIES, THE AUTHOR
CONSIDERED CONVENTIONAL RISK
FACTORS AND INFLAMMATORY
MARKERS.
AND IN ONLY ONE QUARTER OF THE
STUDY WAS THE OUTCOME VALIDATED.
ANOTHER REASON FOR HET GENERATE
WHICH IS PARTICULARLY RELEVANT
TO TRANSLATION AND EPIDEMIOLOGY,
IS DIFFERENCES IN EFFECTIVENESS
AND THAT IS DUE TO DIFFERENCES
IN POPULATION CHARACTERISTICS
AND LOGISTICAL ASPECTS OF STUDY.
FOR EXAMPLE POPULATION
COMPLIANCE, EXPOSURE AND SO ON.
NOW LET ME TURN TO THE MORE
SUBTLE DETERMINANTS, AND MOST
PEOPLE DO NOT TAKE INTO ACCOUNT
THIS.
THE ONE SUCH DETERMINANT IS THE
DIFFERENCES IN THE PHASE OF THE
NATURAL HISTORY WHEN STUDY IS
DONE.
NOW, NOW YOU MAY OR MAY NOT KNOW
THAT IT HAS BEEN DEMONSTRATED
THAT SIMILARLY TO POINT
EPIDEMICS OF INFECTIOUS
DISEASES.
NONCOMMUNICABLE DISEASES ALSO
SHOW A LOT OF NORMAL
DISTRIBUTION OF CASES AFTER THE
INTRODUCTION OF A RISK FACTOR.
AND TWO WELL-KNOWN EXAMPLES ARE
BLADDER TUMORS IN DYESTUFF
WORKERS AND LEUKEMIA AFTER THE
ATOM BOMB EXPLOSIONS.
THUS IF A STUDY IS DONE, BEFORE
THE MINIMUM INCUBATION PERIOD
HAS GONE BY, CASES WOULD BE
UNRELATED TO THE EXPOSE --
EXPOSURE AND THE RESULTS WOULD
BE LOW.
SUBSEQUENTLY, THERE COULD BE
HETEROGENEITY OF STUDIES BEEN
DONE AFTER THE MINIMUM LATENCY
AND AN EXAMPLE IS GIVEN BY THE
NONRELATIONSHIP KNOWN NOW, NOW
WE KNOW, BETWEEN POSTMENOPAUSAL
HORMONAL THEY WERE AND BREAST
CANCER AND IN HUMANS HEALTH
INITIATIVE, FOR INSTANCE, NO
EVIDENCE OF AN INCREASE IN BEST
CHANCER RISK AFTER THE
INTRODUCTION OF HORMONE THERAPY
WAS SEEN IN THE FIRST THREE
YEARS OF THE STUDY.
PERHAPS BECAUSE MINIMAL LATENCY
HAS NOT GONE BY.
SO ANOTHER EXAMPLE OF THE
IMPORTANCE OF CONSIDERING THE
PHASE OF THE NATURAL HISTORY
WHEN EXAMINING RESULTS FOR
DIFFERENT STUDIES COMES FROM THE
TWO NHLBI-FUNDED COHORT STUDIES
THAT DR. MURRAY MENTIONED.
AND AS YOU KNOW, ARTHROSCLEROSIS
HAS A LONG NATURAL HISTORY,
SEVERAL DECADES.
AND THERE MAY BE DIFFERENCES IN
THE STRENGTH OF ASSOCIATION OF
INDIVIDUAL RISK FACTORS WITH
EACH PHASE, WITH DIFFERENT
PHASES OF THE NATURAL HISTORY.
SO, AN EXAMPLE OF A COUPLE OF
RELEVANT QUESTIONS ARE, IS THIS
THE STRENGTH OF ASSOCIATION OF
ONE OR MORE RISK FACTORS THE
SAME OR STAIN AND VULNERABLE IN
PLAQUES?
IS THE STRENGTH THE SAME FOR THE
INITIATION OF ARTHEROSCEROSEIS
IN THE PRECIPITATION OF ACUTE
CLINICAL EVENTS?
FOCUSING ON THE DIFFERENCES IN
THE STRENGTH OF ASSOCIATION, IN
DIFFERENT PHASES OF THE NATURAL
HISTORY OF ARTHROSCLEROSIS, THEY
USED DATA FROM THE MULTIETHNIC
STUDY OF ARTHROSCLEROSIS TO
EXAMINE THE RELATIVE IMPORTANCE
OF SMOKING IN RELATION TO THE
PROGRESS OF ATH SCLEROSIS.
FOLLOWING THE PRINCIPAL THERE IS
NO LESION WITHOUT THE LIPID
CORE, THESE AUTHORS DEVELOPED
THE CONCEPT OF LOW DENSITY
LYPOPROTEIN EQUIVALENT.
THIS IS THE LIPID THAT IS BAD
FOR YOU.
BY ASKING THE QUESTION, WHICH
CONCENTRATION OF LDL WOULD
REPLICATE THE AFFECT OF SMOKING?
AND BY EXTENSION OF ANY RISK
FACTOR IN EACH PHASE OF THE
NATURAL HISTORY OF
ARTHROSCLEROSIS?
AS A PROXY, THE ALTOGETHERRORS
USED B-MODE ULTRASOUND TO
MEASURE THE MEAN INTERMALL
MEDIAL THICKNESS OF THE CAROTID
ARTERIES AND CLASSIFIED IT INTO
MINIMAL, REPRESENTED BY VALUES
BELOW THE 75 PERCEPTILE OF THE
THICKNESS WITHOUT CLINICAL
MANIFESTATIONS.
MODERATE, EQUAL OR MORE THAN
75%, STILL WITHOUT CLINICAL
MACHINE FESTATION AND THEY USE
THIS EXAMPLE OF SEVERE WAS THE
PRESENCE OF PERIPHERAL ARTERY
DISEASE DEFINED BY ANKLE
BREAK-IN DECKS OF LESS THAN 90.
NOW, THE LDL CONCENTRATION
NEEDED TO REPLICATE THE SMOKING
ASSOCIATIONS WAS SHOWN TO
INCREASE AS THE NATIONAL HISTORY
OF ARTHROSCLEROSIS PROGRESSED
AND IT WAS HIGHEST FOR SEVERE
ARTHROSCLEROSIS.
FOR EXAMPLE, TO REPRODUCE THE
EFFECT OF SMOKING IN PERIPHERAL
ARTERIAL DISEASE, THE
CONCENTRATION OF ALMOST 250
MILLIGRAMS OF LDL PER DECILITER
WOULD BE NEEDED.
AND THEY REPLICATED THE SAME
ANALYSIS IN THE STUDY AND FOUND
EXACTLY THE SAME RESULTS.
NOW OF COURSE THESE ANALYSIS HAD
LIMITATIONS SUCH AS THE FACT
THAT THE LEVEL OF SMOKING WAS
NOT CONSIDERED.
BUT THEY MAY PROVIDE A MODEL
THAT CAN BE USED FOR MORE
REFINED ANALYSIS.
NOW THE RESULTS OF THESE TWO
STUDIES REFER TO LOW EXTREMITY
ARTERIAL DISEASE SO THE
IMPORTANT QUESTION ARE THEY ALSO
APPLICABLE TO CLINICAL CORONARY
HEART DISEASE?
SO THERE IS SOME INTERACTIVE
EVIDENCE THIS MAY BE THE CASE.
IN THE STUDY, UNLIKE WHAT IS
OBSERVED IN CANCER, INCIDENTS
RATES OF CLINICAL CORONARY HEART
DISEASE IN FORMER SMOKERS OF
BOTH JEEPEDDERS APPROACH THE
RATE OF NEVER SMOKERS.
-- GENDERS.
THUS SUGGESTING THE
PRECIPITATION OF A CLINICAL
EVENT.
THE SAME PATTERN WAS OBSERVED IN
THE MESA COHORT ARE THE FORMER
SMOKERS OVERLAPPED OF NEVER
SMOKERS.
THAT COULD NOT HAPPEN IN
RESPONDTORY CANCER.
SO WHAT IS THE POLICY
IMPLICATION?
NEVER TOO LATE TO START SMOKING,
RIGHT?
NOW FURTHER LIMITATION OF THESE
ANALYSIS.
THEY DIDN'T TAKE INTO ACCOUNT
THE TIME SINCE QUITTING SMOKING
EVEN THOUGH MANY PARTICIPANTS IN
BOTH HAD QUIT RECENTLY.
HOWEVER, THIS FINDING MADE
BIOLOGICAL SENSE GIVEN THE ROLE
OF SMOKING IN THROMBOSIS OF THE
CORONARIES AND IN SUBSEQUENTLY
IN THE PRECIPITATION OF ACUTE
CORONARY EVENT.
SO, WHAT DOES THAT HAVE TO DO
WITH LET GENERATEY?
IT HAS TO DO WITH THE FACT THAT
IN POPULATIONS WITH A LOW
PREVALENCE OF THE ADVANCED
STAGES OF ARTHROSCLEROSIS,
SMOKING WOULD HAVE STRONGER
ASSOCIATION WHEREAS IN A
POPULATION WHERE MOT NOT MUCH
AROUND, THE RELATIONSHIP BETWEEN
SMOKING AND CORONARY EVENTS WILL
BE WEAKER.
AN ADDITIONAL SOURCE OF
HETEROGENEITY WHICH DOES NOT
NEGATE THE POSSIBILITY OF A
QUASIASSOCIATION IS DIFFERENCES
ACROSS STUDIES AND MODIFIED.
NOW IN THIS EXAMPLE, THIS IS A
TRUE POSITIVE ADDITIVE
INTERACTION AS BEST IN SMOKING
WITH REGARD TO LUNG CANCER DEATH
RATES.
IN THAT THE ASSOCIATION IS MUCH
STRONGER IN THE ABSOLUTE
DIFFERENCE IN THE RATES IS MUCH
HIGHER IN CURRENT SMOKERS THAN
IN NONSMOKERS.
SO LET'S ASSUME FOR A SECOND,
IGNORE THE SMALL NUMBER OF
DEATHS IN PEOPLE WHO NEVER
SMOKE.
LET'S ASSUME THAT THESE DATA ARE
THE GOLD STANDARD.
THEY ARE REAL VALID AND PRECISE.
SO IF THIS IS THE CASE FOR THE
SAKE OF THIS EXAMPLE, IN A STUDY
CARRIED OUT IN A POPULATION
WHERE MOST PEOPLE ARE NEVER
SMOKERS, THE ABSOLUTE DIFFERENCE
WOULD BE RELATIVELY SMALL
APPROACHING 31 PER 100,000
WHEREAS IN ANOTHER STUDY, IN
WHICH MOST PEOPLE ARE SMOKERS,
THE ABSOLUTE DIFFERENCE APPROACH
IS 500, 550 PER 100,000 IGNORING
A MUCH STRONGER ASSOCIATION.
ARGUABLY THIS PHENOMENON IS
RELEVANT TO STUDIES OF
EFFECTIVENESS AND INTERVENTION,
MAY EXPLAIN HETEROGENEITY,
SIGNIFICANT HETEROGENEITY.
NOW FINALLY I'D LIKE TO MENTION
THE DIFFERENCES BETWEEN
OBSERVATIONAL STUDIES AND
VARIABILITY OF THE EXPOSURE OF
THE OUTCOME MAY RESULT IN
HETEROGENEITY.
SOY A FEW YEARS AGO, WE WROTE A
PAPER PUBLISHED IN THE AGE
ADDRESSING THE ISSUE OF
VARIABILITY NECASE CONTROL
STUDIES AND STAYEDED, IF CASES
AND CONTROLS ARE DRAWN FROM A
POPULATION IN WHICH THE RANGE OF
EXPOSURE IS NARROW, THEN A STUDY
MAY YIELD LITTLE INFORMATION
ABOUT THE POTENTIAL HEALTH
EFFECTS.
THIS STATEMENT OBVIOUSLY APPLIED
ALSO TO OTHER TYPES OF
OBSERVATIONAL DESIGNS SUCH AS
COHORT STUDIES.
AND NOT TOO HYPOTHETICAL EXAMPLE
IS THE RELATIONSHIP BETWEEN FAT
INTAKE AND CORONARY HEART
DISEASE IN OBSERVATIONAL
STUDIES.
THEORETICALLY, IN POPULATION A,
WHERE FAT INTAKE DOES NOT VARY
MUCH, AMONG INDIVIDUALS IN THAT
POPULATION, NO CORRELATION, BUT
PERHAPS A WEAK CORRELATION WILL
BE FOUND AT THE INDIVIDUAL LEVEL
WHEREAS IN POPULATION B,
VARIABILITY OF FAT CONSUMPTION
IS SUCH THAT A STRONG
CORRELATION IS CLEARLY OBSERVED
RESULTING IN HETEROGENEITY
BETWEEN THE TWO STUDIES, THOSE
TWO HYPOTHETICAL STUDIES.
AND WE ARE ALL GUILTY, NOT ALL,
BUT MOST OF US ARE GUILTY OF
NEGLECTING THE IMPORTANCE OF
VARIABILITY, INTERVARIABILITYO
STUDY RESULTS IN OUR
OBSERVATIONAL STUDIES.
I WOULD SAY THAT VARIABILITY
SHOULD BE SYSTEMATICALLY
CONSIDERED IN OBSERVATIONAL
STUDIES THROUGH EXAMINATION OF
DISTRIBUTIONS OF THE DIFFERENT
VARIABLES OR USING A MEASURE OF
VARIABILITY IN GOOD OLD
COEFFICIENT VARIABILITY.
PARENTHETICALLY, ALTHOUGH WE
OFTEN EQUATE THAT THE LOGICAL
CORRELATION STUDIES WITH
ETHOLOGICAL PHALLUS IS ALMOST
THE FIRST LECTURE IN
EPIDEMIOLOGY --Y.
WHEN IT IS LOW IN MOST
POPULATIONS, THAT DATA MAY
PROVIDE THE RIGHT ANSWER WHERE
WITHIN POPULATIONS STUDIES AND
INDIVIDUALS DO NOT.
IN THIS HYPOTHETICAL EXAMPLE, WE
HAVE FOUR POPULATIONS IN WHICH
THERE IS NOT MUCH VARIABILITY
WITHIN EACH POPULATION.
BUT WHEN YOU LOOK AT THE
ECOLOGICAL CORRELATION, YOU SEE
A STRONG RELATIONSHIP.
THIS MAY BE THE CASE OF THE WITH
REGARD TO THE RELATIONSHIP
BETWEEN THE SALT AND
HYPERTENSION AND BLOOD PRESSURE.
THUS, TO FINALIZE, NEITHER
HOMOGENEITY NECESSARY IS
EVIDENCE OF CAUSALITY OR
EFFECTIVENESS NOR HET GENERATE
SEEVIDENCE AGAINST.
SUBSEQUENTLY, CAUSAL HOME GENT
8Y SHOULD BE BETTER UNDERSTOOD
BEFORE USING THIS CONCEPT IN
SUPPORT OF OR AGAINST CAUSALITY
EFFECTIVENESS.
WHAT ISLAND LIKE TO FINAL SIZE
TO PROPOSE A COM MARE PAIRISM
BETWEEN TRANSLATIONAL
EPIDEMIOLOGY AND WHAT I WOULD
CALL FOR WANT OF A BETTER TERM,
ACADEMIC EPIDEMIOLOGY.
SO LET'S SEE.
TRANSLATION EPIDEMIOLOGY FOLKS
AND APPLICATION.
ACADEMIC EPIDEMIOLOGY FOCUSES ON
MECHANISM.
THIGH ARE BOTH IMPORTANT, OF
COURSE.
TRANSLATION EPIDEMIOLOGY FAVORS
MEASURES OF ASSOCIATION BASED ON
ABSOLUTE DIFFERENCES
ATTRIBUTABLE RISK AND
EFFECTIVENESS AND THUS IS FOCUS
IS ON ADDITIVE INTERACTIONS.
WHEREAS ACADEMIC EPIDEMIOLOGY
FAVORS RELATIVE MEASURES OF
ASSOCIATION SUCH AS RELATIVE
RISK OF THE ODDS RATIO AND
FOCUSES ON MULTIPLICATIVE
INTERACTION.
THE PUBLIC HEALTH CONFOUNDING IS
USED TO IDENTIFY HIGH RISK
GROUPS SO USEFUL FOR TRANSLATION
OF EPIDEMIOLOGY.
IN ACADEMIC EPIDEMIOLOGY IT IS
USUALLY DONE AS A BIAS.
AND FINALLY I'D LIKE TO QUOTE
ONE OF MY FIVE FAVORITE
EPIDEMIOLOGISTS OF ALL-TIMES,
GEORGE COM STOCK WHO SAID, IF
NOT APPLIED TO PREVENTION AND
PUBLIC HEALTH, EPIDEMIOLOGY
TENDS TO BE FAIRLY BORING.
THANK YOU VERY MUCH.
[ APPLAUSE ]
>> I'M REMINDED OF JUNE STEVENS
WHO IS AN EPIDEMIOLOGIST AT THE
UNIVERSITY OF NORTH CAROLINA WHO
SAID IF IT'S NOT FUN, IT'S
NOT EPIDEMIOLOGY.
WE HAVE TIME FOR QUESTIONS.
WE HAVE TWO MICS SET UP IN THE
AISLES.
PEOPLE CAN STEP UP TO THE
MICROPHONES AND ASK QUESTIONS.
I'LL GET THE STARTED.
YOU MENTIONED THE U.S.
PREVENTIVE SERVICES TASK FORCE
EARLY IN YOUR COMMENTS AND IT
SEEMS TO ME THIS IS A GROUP THAT
IS ENGAGED VERY MUCH IN WHAT YOU
REFER TO AS TRANSLATIONAL
EPIDEMIOLOGY.
AND TAKING THE WORK THAT MANY OF
THE SCIENTISTS HERE AT NIH AND
SUPPORTED BY NIH IN ACADEMICS
ARE DEVELOPING AND THEN THE TASK
FORCE HELPS TO TRANSLATE THAT
INTO USEFUL ADVICE AND
RECOMMENDATIONS FOR CLINICAL
PRACTICE.
IS THAT YOUR VIEW OF THEIR ROLE?
>> YES, ABSOLUTELY.
I THINK IT IS A MOST USEFUL ROLE
AND I THINK EVERY STUDENT OF
EPIDEMIOLOGY SHOULD HAVE A COPY
OF THEIR LITTLE BOOK THAT THEY
PUBLISH.
THEY PUBLISH ARTICLES AND
JOURNALS.
>> THEY ISSUE RECOMMENDATIONS
QUITE REGULARLY.
>> YES.
BUT I THINK THEY VALUES A
PUBLICATION WITH ALL THE CURRENT
RECOMMENDATIONS.
>> THEIR ANNUAL REPORT.
>> YES.
>> LOOKS LIKE WE ARE READY FOR A
QUESTION HERE.
>> HI, I'M JANINE FROM DCEG AND
I WAS WANTED TO ASK YOU ABOUT
THE ADDITIVE INTERACTIONS.
I THINK OBVIOUSLY WE HAVE
IDENTIFIED A SLEW OF GENETIC
VARIANTS IN VARIOUS DISEASES,
AND I THINK THAT THE NEXT PHASE
OBVIOUSLY EVERYBODY IS
INTERESTED IN UNDERSTANDING THE
COMBINATION OF GENES AND THE
ENVIRONMENT AND OF COURSE MANY
OF THESE INTERACTIONS HAVE BEEN
LOOKED AT IN THE MULTIPLICATIVE
SCALE IN LOOKING AT ABSOLUTE
RISK SO I'M CURIOUS IF YOU THINK
IT WILL BE INFORMATIVE TO LOOK
AT SOME OF THE THESE ADDITIVE
INTERACTIONS IN TERMS OF TRYING
TO GET AT TRANSLATIONAL
EPIDEMIOLOGY IN THE FUTURE?
>> WILL IT BE HELPFUL TO LOOK AT
ADDITIVE INTERACTION IN THE
CONTEXT OF GENE ENVIRONMENT
INTERACTIONS?
>> WELL, I'M NOT A GENETIC
EPIDEMIOLOGIST BUT I THINK IF
YOU'RE INTERESTED IN USING THE
RESULTS OF GENETIC STUDIES FOR
PRIMARY PREVENTION, YES.
ABSOLUTELY.
I THINK IF YOU FIND A GENOTYPE
THAT MODIFIES THE AFFECT OF SOME
ENVIRONMENTAL RISK FACTOR, YOU
WANT TO KNOW ABOUT THAT.
NOW OF COURSE YOU HAVE TO THINK
NOT JUST IN TERMS OF WHAT I
SHOW, WHICH WAS A VERY
SIMPLICITY EXAMPLE, BUT ALSO IN
TERMS OF WHAT YOU CALL THE
POPULATION.
BECAUSE IF EUGENEO TYPE STRONGLY
MODIFIES THE RISK FACTOR BUT
PREVALENCE IS VERY SMALL, SO
IT'S NOT GOING TO HAVE A BIG
IMPACT IN PUBLIC HEALTH.
>> YES.
>> HI, GERMANE FROM NICHD.
THANK YOU FOR THAT REALLY NICE
TALK.
I'M REFLECTING ON THE SOCIETY OF
EP DEEM LOGICS RESEARCH PAST
ANNUAL MEETING WITH.
>> PRESIDENT OBAMA: TALKING
ABOUT CONSEQUENTIAL EPIDEMIOLOGY
AND -- AND WHILE I'M A BIG FAN,
I'M WONDERING IF YOU HAVE ANY
THOUGHTS ABOUT WHETHER OR NOT
ADDING TOO MANY ADJECTIVES IN
FRONT OF THE FIELD OF
EPIDEMIOLOGY MAY BE DISTRACTING
TO THE PUBLIC THAT WE ARE TRYING
TO IMPACT?
>> DO YOU KNOWLEDGE PUTTING TOO
MANY ADJECTIVES IN FRONT OF THE
WORD, EPIDEMIOLOGY, CONFUSES THE
QUESTION?
[ LAUGHS ]
TRADITIONALLY THE DEFINITION
INTRINSICALLY HAS THE IDEA OF
APPLICATION.
BUT I THINK IT IS USEFUL TO USE
IN TERMS TRANSLATIONAL
EPIDEMIOLOGY BECAUSE IN THE LAST
FEW YEARS, EPIDEMIOLOGISTS
FAVORED, I WOULD SAY, ETIOLOGY
BASICALLY, MECHANISMS.
AND THEY HAVE BEEN AWAY.
AND I THINK THAT HAS A
HISTORICAL CAUSE.
I WAS TALKING TO SANDRA WHO IS
ALSO VERY INTERESTED IN THIS
AREA AND HE TOLD ME THAT HIS
EXPLANATION OR HIS HYPOTHESES IS
THAT IF A GIVEN POINT IN TIME,
EPIDEMIOLOGY NEEDED TO BE
PERCEIVED AS A SCIENTIFIC AREA.
AND PLEDGE HEALTH IS TERRIBLY
IMPORTANT AS IT IS, DOESN'T HAVE
A LOT OF PRESTIGE AS SOMETHING
LIKE PLASTIC SURGERY.
THERE WAS A SURVEY A FEW YEARS
AGO AND THE ONLY MEDICAL
SPECIALTY THAT IS WORSE THAN
PUBLIC HEALTH WERE PSYCHIATRY
AND PEDIATRICS.
SO IT IS ALL THE WAY IN THE
BOTTOM.
AND I REALLY THINK THAT
ESSENTIALLY, EPIDEMIOLOGIST
SHOULD BE THAT, APPLY KNOWLEDGE,
PROGRAMS, PREVENTION AND SO ON.
BUT UNFORTUNATELY, WE NEED TO
HIGHLIGHT THE APPLICATION
BECAUSE EPIDEMIOLOGY HAS MOVED
AWAY.
NOT ENTIRELY, WE HAVE GOOD
EXAMPLE HERE IN DR. MURRAY AND
BUT MANY ACADEMIC
EPIDEMIOLOGISTS STRAY A LOT FROM
THE NOTION OF APPLICATION.
[ INDISCERNIBLE ]
I REALLY LIKE THE TERM
TRANSLATIONAL EPIDEMIOLOGY.
I WAS GOING TO SAY THANK YOU
VERY MUCH FOR THE EXCELLENT
PRESENTATION.
MY QUESTION IS HOW COULD OR IF
WE COULD HAVE A COPY OF YOUR
PRESENTATION?
>> HE IS ASKING IF YOU CAN
PROVIDE WITH A COPY OF YOUR TALK
TO DISTRIBUTE.
>> SURE, I CAN DO THAT.
>> WE WILL ARRANGE THAT.
OTHER QUESTIONS?
SO WHAT ADVICE WOULD YOU GIVE TO
STUDENTS WHO ARE CURRENTLY
STUDYING EPIDEMIOLOGY AND
LEARNING THE SCIENCE OF
EPIDEMIOLOGY IN AN ACADEMIC
INSTITUTION THAT COULD HELP THEM
KEEP THE NEED FOR TRANSLATION IN
FRONT OF THEM AS THEY ARE GOING
FORWARD?
>> WELL, I THINK THE ADVICE
WOULD BE GIVEN TO THE FACULTY.
[ LAUGHS ]
NOT TO THE STUDENTS.
BECAUSE THE STUDENTS MAY BE VERY
INTERESTED IN APPLICATION AND
YET THERE ARE NO PROGRAMS AT
THEIR SCHOOL THAT FOCUS ON
TRANSLATIONAL KNOWLEDGE.
IT IS CHANGING, THOUGH.
IT'S CHANGING.
HOPKINS NOW HAS A PROFESSIONAL
EPITRACK EMPHASIZING APPLICATION
OF TRANSLATION.
AND I WAS -- I LECTURED AT
HARVARD A FEW MONTHS AGO AND
THEY HAVE AN INTEREST GROUP ON
TRANSLATION EPIDEMIOLOGY.
SO I THINK THINGS ARE CHANGING.
AND I THINK BOTH ARE IMPORTANT,
OF COURSE, ETIOLOGY IS NOT ONLY
IMPORTANT EXCEPT THE AMBULANCE
IS NOT RIGHT.
-- THE BALANCE IS NOT RIGHT.
IT'S TOO MUCH OF A -- IT'S NOT
AS IMPORTANT AS IT IS.
SO APPLICATION HAS TO BE
RESTORED.
>> ARE THERE OTHER QUESTIONS
FROM THE AUDIENCE?
ALL RIGHT, THANK YOU VERY MUCH.
[ APPLAUSE ]
>> LET ME REMIND ERCH WE HAVE A
RECEPTION IN THE LIBRARY JUST
THROUGH THESE DOUBLE DOORS.
I ENCOURAGE EVERYONE TO COME
OVER.
WE HAVE SOMETHING TO SNACK ON
AND YOU CAN VISIT WITH
DR. MOYSES SZKLO AND CHAT WITH
HIM DIRECTLY.