HELLO AND WELCOME.
MY NAME IS JOSHUA GORDON,
DIRECTOR OF THE NATIONAL
INSTITUTE OF MENTAL HEALTH AND
CO-CHAIR OF THE EXECUTIVE
COMMITTEE FOR ADVANCING BASIC
BEHAVIORAL SOCIAL SCIENCES AT
THE NIH.
TWO YEARS AGO, THE NIH RELEASED
A SET OF EXPERT PANEL
RECOMMENDATIONS FOR THE AGENCY
TO STRENGTHEN ITS PORTFOLIO IN
BASIC RESEARCH IN THE BEHAVIORAL
AND SOCIAL SCIENCES.
THESE RECOMMENDATIONS INCLUDED
EXPANDING OUR UNDERSTANDING OF
CAUSAL INFERENCE BEYOND JUST
RANDOMIZED CLINICAL TRIALS.
OU -- PROJECTS IN THE LITERATURE
AND RECOMMENDED WE HEAR FROM
PROFESSOR JON WILLIAMSON.
SO WE WELCOME HIM AS THE
DISTINGUISHED LECTURER TO BEGIN
OUR SERIES OF EXPANDING THE NIH
COMMUNITY AND STAKEHOLDERS
UNDERSTANDING WITH REGARD TO
CAUSALITY.
FOR FURTHER INTRODUCTION, I'LL
TURN IT OVER TO DR. JAMES
MALONEY, DIRECTOR OF THE OFFICE
OF BASIC BEHAVIORAL AND SOCIAL
SCIENCES AND ASSOCIATE DIRECTOR
FOR THE SAME AT NIH.
>> THANKS SO MUCH.
>> IN LIEU OF HAVING A BREAK
DURING OUR TECHNICAL
DIFFICULTIES, WELCOME, AND THANK
YOU, JOSH, FOR YOUR OPENING
REMARKS.
I'M BILL ELWOOD FROM THE OFFICE
OF SOCIAL -- BEHAVIORAL AND
SOCIAL SCIENCES AT NIH, AND PART
OF THE TEAM RESPONSIBLE FOR
BRINGING YOU THIS EXCITING
LECTURE.
PROFESSOR JON WILLIAMSON IS AT
THE UNIVERSITY OF KENT, WHERE HE
WORKS IN THE PHILOSOPHY OF
SCIENCE AND MEDICINE.
THERE HE IS THE CO-DIRECTOR OF
THE CENTER FOR REASONING AND A
MEMBER OF THE THEORETICAL
REASONING RESEARCH CLUSTER.
HE WORKS IN THE PHILOSOPHY OF
CAUSALITY, THE FOUNDATIONS OF
PROBABILITY, DEDUCTIVE LOGIC AND
THE USE OF CAUSALITY,
PROBABILITY AND INFERENCE
METHODS IN SCIENCE AND MEDICINE.
AS JOSH TOLD YOU, THIS CONCEPT
TEAM WAS REALLY IMPRESSED WITH
THE SCOPE OF PROFESSOR
WILLIAMSON'S WORK, AND WE
APPRECIATE HIM JOINING US TODAY
FOR OUR PLENARY LECTURE IN THIS
SERIES.
YOU'RE WELCOME TO ANSWER -- TO
POSE QUESTIONS DURING JON'S TALK
THROUGH THE VIDEOCAST FUNCTION
IN YOUR SCREEN, BUT WE WILL TAKE
THEM ONCE JON HAS FINISHED.
THANKS SO MUCH FOR JOINING US,
JON.
TAKE IT AWAY.
>> THANK YOU VERY MUCH FOR THE
KIND INTRODUCTION, BILL.
IT'S A GREAT PLEASURE TO BE
TALKING TO YOU TODAY.
SO I AM INTERESTED IN PHILOSOPHY
OF SCIENCE AND MEDICINE, AND MY
KEY AREA OF RESEARCH HAS BEEN
CAUSATION AND PROBABILITY IN
SCIENCE AND MEDICINE.
I'M GOING TO TALK TODAY ABOUT A
NEW FRAMEWORK FOR CAUSAL
INFERENCES IN THE HEALTH AND
SOCIAL SCIENCES.
SO FIRST OF ALL, I'LL INTRODUCE
THE NEW FRAMEWORK, GIVE A
GENERAL INTRODUCTION TO THE
FRAMEWORK, I'LL EXPLAIN HOW THE
NEW APPROACH RELATES TO OTHER
APPROACHES, AND THEN I'LL LOOK
AT HOW IT PROVIDES AN ACCOUNT OF
EXTERNAL VALIDITY, SO
EXTRAPOLATING A CAUSAL CLAIM
FROM ONE CONTEXT TO ANOTHER
CONTEXT.
AND THEN FINALLY, I WILL LOOK IN
A BIT MORE DETAIL AS TO HOW
UNDER THIS NEW FRAMEWORK, ONE
GOES AHEAD AND EVALUATES THE
EFFECTIVENESS, FOR EXAMPLE, OF A
HEALTH INTERVENTION.
AND I'LL LOOK AT A CONTROVERSIAL
EXAMPLE OF NAMELY THE MANDATES
FOR FACE MASKS AND WHETHER
THEY'RE EFFECTIVE AT REDUCING
THE SPREAD AND REDUCING SYMPTOMS
OF COVID-19.
AND BY LOOKING IN DETAIL AT A
CASE STUDY, WE'LL GET A SENSE OF
HOW THIS NEW APPROACH WORKS IN
PRACTICE.
OKAY.
SO FIRST OF ALL TO PROVIDE AN
INTRODUCTION TO THE FRAMEWORK
FOR CAUSAL INFERENCE, THIS
FRAMEWORK IS CALLED EVIDENTIAL
PLURALISM, AND I'LL EXPLAIN WHAT
THIS MEANS FIRST OF ALL.
THE GUIDING IDEA BEHIND
EVIDENTIAL PLURALISM STEMS FROM
THE PLATITUDE THAT WE'RE ALL
TAUGHT AT A YOUNG AGE, NAMELY,
CORRELATION IS NOT CAUSATION.
WHEN YOU FIND A CORRELATION
BETWEEN TWO VARIABLES, A AND B,
CONDITIONAL POTENTIAL
CONFOUNDING VARIABLES, THIS
MIGHT BE DUE TO ONE OF A RANGE
OF POSSIBLE EXPLANATIONS.
ONLY ONE OF WHICH IS CAUSATION.
THERE ARE A NUMBER OF OTHER
POSSIBLE EXPLANATIONS FOR A
CORRELATION.
IT COULD BE DUE TO REVERSE
CAUSATION, CONFOUNDING
PERFORMANCE BIAS, DETECTION BIAS
OR ANY OTHER KIND OF BIAS, SO
THERE'S A REPOSITORY ON THE
INTERNET THAT LISTS THE KINDS OF
BIAS THAT STUDIES A PRONE TO AND
I COUNTED 65 DIFFERENT KIND OF
BIAS.
SO MANY POSSIBLE EXPLANATIONS
FOR THE CORRELATION.
IT COULD BE BOUND TO SHEER
CHANCE.
IT COULD BE THAT THE RESEARCHERS
HAVE BEEN FISHING FOR
CORRELATIONS OR THERE COULD BE
TEMPLE TRENDS IN THE DATA THAT
ARE RESPONSIBLE FOR THE
CORRELATION RATHER THAN A CAUSAL
CONNECTION.
OR MAYBE THE CORRELATION IS DUE
TO SOME CONNECTION BUT IT'S NOT
A CAUSAL CONNECTION.
SO MAYBE THE TWO VARIABLES HAVE
OVERLAPPING MEANING, FOR EXAM
EXAMPLE.
OR THEY'RE CONNECTED LOGICALLY.
OR BY SOME MATHEMATICAL
RELATIONSHIP.
THIS HAPPENS QUITE FREQUENTLY
WHEN REAL DATA IS INVOLVED.
SO WHAT PICKS OUT CAUSATION FROM
SOME OF THESE OTHER EXPLANATIONS
OF A CORRELATION?
WELL, IF AGO.
IS A CAUSE OF B, THEN THERE'S
GOING TO BE SOME COMPLEX OF
MECHANISMS THAT EXPLAINS
INSTANCES OF B BY APPEALING TO
INSTANCES OF A, AND THAT CAN
ACCOUNT FOR THE MAGNITUDE OF THE
OBSERVED CORRELATION.
SO THE DISTINCTIVE FEATURE ABOUT
CAUSATION IS THAT THERE'S ALWAYS
SOME MECHANISM OR COMPLEX OF
MECHANISMS THAT UNDERPIN
CAUSATION.
SO IN ORDER TO ESTABLISH
CAUSATION, YOU NEED TO ESTABLISH
TWO THINGS.
NOT ONLY DO YOU NEED TO
ESTABLISH CORRELATION,
CONDITIONAL AND POTENTIAL
CONFOUNDERS, BUT ALSO THE
EXISTENCE OF A MECHANISM THAT
CAN EXPLAIN THAT CORRELATION.
AND THAT'S THE GUIDING IDEA
BEHIND EVIDENTIAL PLURALISM.
SO EVIDENTIAL PLURALISM IS
PROBABLY BEST ENCAPSULATED BY
THIS DIAGRAM.
AT THE TOP OF THE DIAGRAM IS THE
CLAIM THAT WE WANT TO SUPPORT,
NAMELY CAUSATION.
THIS IS ESTABLISHED BY
ESTABLISHING THE EXISTENCE OF
THE CORRELATION AND THE
EXISTENCE OF A LINKING
MECHANISM.
NOW, THE BEST WAY TO ESTABLISH A
CORRELATION IS TO PERFORM SOME
ASSOCIATION STUDY, SO THIS IS A
LARGE STATISTICAL STUDY THAT
MEASURES A AND B TOGETHER,
TOGETHER PERHAPS WITH POTENTIAL
CONFOUNDERS, AND TRIES TO
ESTIMATE THE EXTENT OF A
CORRELATION BETWEEN CAUSE AND
EFFECT.
CERTAIN KINDS OF STUDY DESIGN
ARE PARTICULARLY VALUED.
FOR EXAMPLE, RANDOMIZED CONTROL
TRIALS, BECAUSE RANDOMIZED
CONTROL TRIALS CAN INDIRECTLY
CONFIRM THE EXISTENCE OF A
LINKING MECHANISM.
AND THEY DO THIS BY REDUCING THE
PROBABILITY THAT ANY OBSERVED
CORRELATION IS DUE TO
CONFOUNDING BY UNFORESEEN
FACTORS.
SO IT POSSIBLE TO GET INDIRECT
EVIDENCE CONFIRMING THE
EXISTENCE OF A LINKING MECHAN
MECHANISM.
BUT THERE'S A MUCH MORE DIRECT
WAY TO CONFIRM THE PRESENCE OF A
LINKING MECHANISM, AND THAT'S TO
HYPOTHESIZE FEATURES OF THE
MECHANISM CONNECTING A TO B.
NOW THESE FEATURES COULD BE
INTERMEDIARY VARIABLES, THEY
COULD BE ENTITIES THAT ARE
INVOLVES IN THE MECHANISM OR
ACTIVITY INVOLVED, OR
ORGANIZATIONAL FEATURES OF THE
MECHANISM.
SO THERE ARE A WIDE VARIETY OF
POSSIBLE MECHANISM FEATURES THAT
COULD BE HYPOTHESIZED.
AND THEN STUDIES THAT LOOK FOR
THE PRESENCE OR ABSENCE OF THESE
FEATURES ARE CLASSIFIED AS
MECHANISTIC STUDIES BY
EVIDENTIAL PLURALISM.
AND SO A SECOND WAY TO CONFIRM
THE EXISTENCE OF A MECHANISM IS
HYPOTHESIZING MECHANISM FEATURES
AND TESTING TO SEE WHETHER THOSE
FEATURES ARE PRESENT.
SO EVIDENTIAL PLURALISM APPEALS
TO TWO KINDS OF STUDY, AN
ASSOCIATION STUDY AND A
MECHANISTIC STUDY.
THESE AREN'T DETERMINED BY ANY
PARTICULAR STUDY DESIGN.
THESE ARE DIFFERENT ROLES THAT
STUDIES TAKE.
SO ASSOCIATION STUDIES ARE
MEASURING CAUSE AND EFFECT
TOGETHER, WHEREAS MECHANISTIC
STUDIES ARE LOOKING AT A FINER
GRAIN AT FEATURES OF THE
MECHANISM THAT LINK THE CAUSE
AND EFFECT.
AND EVIDENTIAL PLURALISM INVOKES
TWO KINDS OF PLEURALISM.
IT SAYS IF YOU WANT TO ESTABLISH
A CAUSAL CLAIM, YOU NEED TO
ESTABLISH CORRELATION AND
MECHANISM.
THAT'S THE TOP PART OF THE
DIAGRAM.
SO IF YOU WANT TO ASSESS A
CAUSAL CLAIM YOU NEED TO
CONSIDER NOT ONLY ASSOCIATION
STUDIES BUT ALSO MECHANISTIC
STUDIES.
AND THAT'S THE GUIDING IDEA
BEHIND EVIDENTIAL PLURALISM.
ONE IMPORTANT THING TO NOTE IS
THAT EVIDENTIAL PLURALISM GOES
AGAINST THE STANDARD TENETS OF
EVIDENCE-BASED MEDICINE AND
EVIDENCE-BASED POLICY.
SO EVIDENCE-BASED MEDICINE WAS
PUT FORWARD TO DE-EMPHASIZE THE
ROLE OF MECHANISTIC EVIDENCE.
SO WHEN IT WAS INTRODUCED, THE
IDEA WAS TO PRIORITIZE
RANDOMIZED CONTROL TRIALS,
REVIEWS OF RANDOMIZED CONTROLLED
TRIALS, AND FOCUS ON
SCRUTINIZING THOSE KINDS OF
STUDIES RATHER THAN OTHER KINDS
OF OBSERVATIONAL STUDY WHICH ARE
VIEWED AS INFERIOR TO RANDOMIZED
CONTROL TRIALS, AND REALLY
EVIDENCE-BASED MEDICINE, THE
IDEA OF EVIDENCE-BASED MEDICINE
IS TO SIDELINE IMPORTANT STUDY
DESIGNS THAT CAN PRODUCE GOOD
QUALITY EVIDENCE OF MECHANISM
SUCH AS ANIMAL RESEARCH OR IN
VITRO TEST TUBE RESEARCH.
SO IN THIS EXAMPLE OF AN
EVIDENCE HIERARCHY USED IN
TEACHING EVIDENCE-BASED
MEDICINE, ANIMAL RESEARCH AND IN
VITRO RESEARCH ARE PUT RIGHT AT
THE BOTTOM OF THE EVIDENCE
HIERARCHY, BELOW EVEN IDEAS AND
OPINIONS.
AND A SYSTEMATIC REVIEW IN
EVIDENCE-BASED MEDICINE OR
EVIDENCE-BASED POLICY WON'T
BOTHER SCRUTINIZING MECHANISTIC
EVIDENCE.
EVIDENTIAL PLURALISM IN CONTRAST
WANTS TO TREAT MECHANISTIC
EVIDENCE ON A PAR WITH
ASSOCIATION STUDIES.
SO EVIDENTIAL PLURALISM TAKES
MECHANISTIC STUDIES TO BE OF
EQUAL VALUE TO ASSOCIATION
STUDIES.
SO EVIDENTIAL PLURALISM
ADVOCATES LOOKING AT THE KINDS
OF STUDY THAT EVIDENCE-BASED
MEDICINE LOOKS AT, SO THESE ARE
REVIEWS, META ANALYSES, RCTs
AND SO ON, BUT IT ALSO ADVOCATES
LOOKING AT STUDIES THAT CAN
EXPLORE FEATURES OF A LINKING
MECHANISM BETWEEN CAUSE AND
EFFECT.
AND THIS MIGHT INCLUDE
MANIPULATION STUDIES, SO IN
VITRO STUDIES, OBSERVATIONAL
STUDIES, BIOMEDICAL IMAGING, FOR
EXAMPLE, CLINICAL STUDIES THAT
LOOK FOR INTERMEDIARY VARIABLES,
AND THIS COULD BE RANDOMIZED
TRIALS, FOR EXAMPLE.
CONFIRMED THEORY, FOR EXAMPLE,
IMMUNOLOGICAL TH THEORY WOULD HP
SUPPORT SPECIFIC MECHANISM
HYPOTHESES, ANIMAL STUDIES CAN
HELP AS WELL, AND SIMULATION
STUDIES LIKE AGENT-BASED MODELS
CAN ALSO BE HELPFUL IN TRYING TO
UNDERSTAND FEATURES OF
MECHANISMS.
SO EVIDENCE-BASED MEDICINE AND
EVIDENCE-BASED POLICY FOCUS ON
THE LEFT SIDE OF THIS PICTURE,
AND EVIDENTIAL PLURALISM IS
SAYING STANDARD EVIDENCE-BASED
MEDICINE, EVIDENCE-BASED POLICY
IS ONLY HALF OF THE PICTURE' WE
SHOULD BE LOOKING ALONGSIDE
THESE KINDS OF STUDIES AT
MECHANISTIC STUDIES.
SO THE IDEAL CHAMPION BY
EVIDENCE-BASED MEDICINE IS YOU
FOCUS ON THE ASSOCIATION STUDIES
AND IF ALL GOES WELL, THE
ASSOCIATION STUDIES ARE GOING TO
ESTABLISH NOT ONLY THE PRESENCE
OF A CORRELATION BETWEEN THE TWO
VARIABLES YOU'RE INTERESTED IN,
BUT ALSO ESTABLISH THE PRESENCE
OF A LINKING MECHANISM.
AND IF YOU'VE GOT SEVERAL HIGH
QUALITY RANDOMIZED CONTROLLED
TRIALS, THAT CAN HAPPEN.
ONCE YOU ESTABLISH THOSE TWO
THINGS, YOU ESTABLISH CAUSATION.
THAT'S THE IDEAL, BUT THE IDEAL
IS RARELY BORNE OUT IN PRACTICE,
AND THIS IS FOR TWO REASONS.
THE FIRST IS THAT ASSOCIATION
STUDIES ARE OFTEN NOT AS HIGH
QUALITY AS THE IDEAL WOULD LIKE,
AND IT'S OFTEN NOT THE CASE THAT
THE ASSOCIATION STUDIES SUFFICE
TO ESTABLISH CAUSATION.
SECONDLY, IT'S NOT THE CASE IN,
FOR EXAMPLE, DRUG APPROVAL
MEETINGS OR OTHER EVALUATION
MEETINGS THAT ASSOCIATION
STUDIES EXHAUST THE EVIDENCE.
TYPICALLY WE KNOW QUITE A LOT
ABOUT MECHANISMS OF ACTION OF A
DRUG, FOR EXAMPLE, OR OTHER
KINDS OF INTERVENTIONS.
AND THESE ARE USED TO GUIDE THE
APPROVAL PROCESS, BUT IN A VERY
UNSYSTEMATIC AND UNEXPLICIT WAY,
IT OFTEN DEPENDS WHO'S AROUND
THE TABLE AS TO WHAT MECHANISM
HYPOTHESES GET DISCUSSED, AND
THERE'S NO SERIOUS
CONSIDERATION, SYSTEMATIC
CONSIDERATION OF MECHANISTIC
STUDIES.
SO REALLY, THERE ARE TWO
DEFICIENCIES IN THE STANDARD
APPROACH.
THE FIRST IS THAT IN THE
BACKGROUND, THERE IS MECHANISTIC
EVIDENCE GOING ON, AND THIS CAN
SUPPORT OR UNDERMINE THE CAUSAL
CLAIM, AND THE SECOND ISSUE IS
THAT ASSOCIATION STUDIES ON
THEIR OWN DON'T OFTEN SUFFICE TO
ESTABLISH CAUSATION.
SO LET'S CONSIDER A COUPLE OF
EXAMPLES WHERE EVIDENCE OF
MECHANISMS CAN CONFIRM CAUSAT
CAUSATION.
THERE'S A TONGUE IN CHEEK
EXAMPLE PUT FORWARD BY SMITH AND
PELL IN 2003.
THEY SAY PARACHUTES REDUCE THE
RISK OF INJURY OF IMR GRAVITATIL
CHALLENGE BUT THEIR
EFFECTIVENESS HAS NOT BEEN
PROVED WITH RANDOMIZED
CONTROLLED TRIALS.
OF COURSE WE'RE NOT GOING TO
CONDUCT RANDOMIZED CONTROLLED
TRIALS ON THE USE OF PARACHUTES.
AND THE REASON WE'RE NOT GOING
TO DO THIS IS BECAUSE WE'VE GOT
VERY GOOD MECHANISTIC EVIDENCE
AS TO HOW PA PARACHUTES WORK AND
THAT IS VERY INFORMATIVE.
SO IT SUFFICES TO HAVE
UNSYSTEMATIC OBSERVATIONS OF THE
USE OF PARACHUTES IN THE PAST,
TOGETHER WITH MECHANISTIC
EVIDENCE ABOUT HOW THEY WORK,
AND WE ALL KNOW THAT PARACHUTE
USE CAN REDUCE THE RISK OF
INJURY WHEN FALLING FROM SUCH A
HEIGHT.
SO THEIR POINT WAS THAT REALLY
THIS FOCUS ON -- EXCLUSIVE FOCUS
ON ASSOCIATION STUDIES ISN'T THE
WHOLE STORY.
EVIDENCE-BASED EVALUATION SHOULD
INVOLVE MORE THAN JUST
RANDOMIZED CONTROL TRIALS.
HERE'S A MORE SERIOUS EXAMPLE,
AND THIS IS THE USE OF ECMO TO
HELP WITH PERSISTENT PULMONARY
HYPERTENSION.
SO IF BABIES ARE BORN VERY
PREMATURELY, SOMETIMES THEIR
LUNGS CAN'T OXYGENATE THE BLOOD
ADEQUATELY, AND SO ONE APPROACH
IS DEALING WITH THIS IS TO
OXYGENATE THE BLOOD OUTSIDE THE
BODY UNTIL THE LUNGS ARE MATURE
ENOUGH TO OPERATE ON THEIR OWN.
AND THE ECCHYMOSIS TEM IS A
MECHANISM FOR TAKING THE BLOOD
FROM THE BODY, OXYGENATING IT
AND PUTTING IT BACK INTO THE
BODY, WHILE THE LUNGS DEVELOP.
NOW, OBSERVATIONAL STUDIES
SUGGESTED AN INCREASE IN
SURVIVAL RATE FROM ABOUT 20% TO
80%.
BUT BECAUSE THE STANDARD
EVIDENCE-BASED MEDICINE WAS THE
NORM, IT WAS FELT NECESSARY TO
CONDUCT RANDOMIZED CONTROL
TRIALS, AND SO RANDOMIZED
CONTROL TRIALS, I THINK SEVERAL
TRIALS WERE CARRIED OUT, AND OF
COURSE BABIES IN THE CONTROL
GROUP DIED BECAUSE THEY WEREN'T
GIVEN THE ECCHYMOSIS T ECMO SYSO
OXYGENATE THEIR BLOOD.
THIS IS A CASE WHERE PROGRAMS
RANDOMIZED CONTROLLED TRIALS
WERE COMPLETELY UNNECESSARY
BECAUSE CAUSATION WAS ALREADY
WELL ESTABLISHED BEFORE THE
TRIAL STARTED, SO THERE WAS GOOD
OBSERVATIONAL EVIDENCE
SUGGESTING A VERY LARGE EFFECT
SIZE, AN INCREASE IN SURVIVAL
RATE FROM 20% TO 80%, AND THE
MECHANISM WAS VERY WELL-KNOWN.
LIKE THE PARACHUTE MECHANISM,
IT'S CLEAR WHAT THE MECHANISM OF
TREATMENT IS DOING HERE.
AND SO THIS COULD BE A CASE IN
WHICH ONE COULD ARGUE THAT
REALLY THE TRIAL SHOULD NEVER
HAVE BEEN CONDUCTED.
SO WHAT'S GOING ON IN THESE
EXAMPLES?
WELL, YOU HAVE THE UNSYSTEMATIC
OBSERVATIONAL DATA.
THESE DON'T SUFFICE TO ESTABLISH
CORRELATION ON THEIR OWN.
THEY MAY BE SUPPORTED
CORRELATION, BUT THEY DON'T
SUFFICE TO ESTABLISH
CORRELATION, NOR DO THEY SUFFICE
TO ESTABLISH THE PRESENCE OF A
LINKING MECHANISM.
WHAT'S GOING ON HERE IS THAT WE
CAN EASILY HI HYPOTHESIZE FEATUS
OF THE PARACHUTE MECHANISM, THE
ECMO MECHANISM AND WE CAN
CONFIRM THOSE FEATURES.
THESE DO ALLOW US TO ESTABLISH
THE PRESENCE OF A LINKING
MECHANISM AND SIGNIFICANTLY
RAISE OUR CONFIDENCE THAT THE
OBSERVED CORRELATION IS GOING TO
PERSIST CONDITIONAL ON POTENTIAL
CONFOUNDERS.
AND THIS ALLOWS US TO ESTABLISH
CAUSATION.
SO THESE ARE KIND OF EXTREME
EXAMPLES WHERE EVIDENCE OF
MECHANISMS CAN HELP SUPPORT
CAUSATION.
EVIDENCE MECHANISMS CAN ALSO
UNDERMINE CAUSATION.
SO AGAIN, THERE ARE TONGUE IN
CHEEK EXAMPLES, TESTING REMOTE
RETROACTIVE INTERCESSIONARY
PRAYER, FINDING IT IN A
RANDOMIZED CONTROLLED TRIAL TO
BE ASSOCIATED WITH LENGTH OF
STAY OF PATIENTS IN HOSPITALS.
SO THIS IS PRAYING FOR PATIENTS'
RECOVERY AFTER THEY'VE LEFT
HOSPITAL, AND THERE WAS AN
OBSERVED CORRELATION BETWEEN THE
LENGTH OF STAY OF PATIENTS IN
HOSPITAL AND WHETHER THEY WERE
PRAYED FOR SUBSEQUENTLY.
THERE WERE RANDOMIZED CONTROLLED
TRIALS THAT HAVE CONFIRMED
PRECOG NIGMS, RANDOMIZED
CONTROLLED TRIALS THAT CONFIRMED
HOMEOPATHY.
WE DON'T LEND THESE TRIALS VERY
MUCH CREDENCE.
WHY DON'T WE DO THAT?
WELL, IT'S BECAUSE WE'VE GOT
VERY STRONG NEGATIVE EVIDENCE OF
MECHANISMS HERE.
SO ALTHOUGH WE MIGHT HAVE A
LITTLE SUPPORT FROM THESE TRIALS
FOR A CORRELATION, EVIDENCE OF
MECHANISMS IS UNDERMINING THIS
SUPPORT.
WE KNOW AS FAR AS OUR BEST
SCIENCE TELLS US, ANY SPECIFIC
MECHANISM HYPOTHESES THAT HAVE
BEEN PUT FORWARD HAVE BEEN
REJECTED, AND AS FAR AS WE KNOW,
THERE'S NO MECHANISM LINKING A
TO B IN THESE EXAMPLES.
AND SO WE TEND TO RULE OUT
CAUSATION IN THIS CASE.
AGAIN, EVIDENTIAL PLURALISM CAN
EXPLAIN OUR PATTERN OF REASONING
HERE BY APPEALING TO MECHANISTIC
EVIDENCE.
SO EVIDENTIAL PLURALISM HAS BEEN
APPLIED BOTH IN THE AREA OF
MEDICINE, AND THIS LEADS TO AN
APPROACH CALLED EBM+.
SO THE PLUS HERE IS CONSIDERING
MECHANISMS ALONGSIDE THE
STANDARD METHODS OF EBM.
SO I NEED TO EMPHASIZE THAT THIS
ISN'T REJECTING THE STANDARD
STUDIES THAT EBM LOOKS AT.
IT SAYING THAT THE STANDARD
STUDIES AREN'T ENOUGH ON THEIR
OWN.
WE ALSO NEED TO SYSTEMATICALLY
SCRUTINIZE THE MECHANISTIC
EVIDENCE THAT WE'VE GOT BECAUSE
THAT CAN HELP SUPPORT OR
UNDERMINE OUR CAUSAL CLAIMS.
IN THE AREA OF THE SOCIAL
SCIENCES, THERE'S AN ANALOGOUS
APPROACH THAT DEALS WITH
EVIDENCE-BASED POLICY CALLED
EBP+, AND THIS ADVOCATES LOOKING
AT EVIDENCE OF MECHANISMS
ALONGSIDE ASSOCIATION STUDIES
WHEN WE'RE TRYING TO EVALUATE
WHETHER A POLICY INTERVENTION
WORKS OR NOT.
HERE ARE A COUPLE OF OPEN ACCESS
BOOKS ON THESE TWO APPROACHES IF
YOU'RE INTERESTED IN LEARNING
MORE ABOUT THEM.
OKAY.
I'M NOW GOING TO MOVE ON TO SEE
HOW EVIDENTIAL PLURALISM RELATES
TO OTHER TECHNIQUES.
SO WE'VE ALREADY SEEN THAT
EVIDENCE-BASED MEDICINE,
EVIDENCE-BASED POLICY FOCUSES ON
THE LEFT-HAND SIDE OF THE
CAUSATION DIAGRAM.
THESE FOCUS PRETTY MUCH
EXCLUSIVELY ON ASSOCIATION
STUDIES, VIEW MECHANISTIC
EVIDENCED INFERIOR TO
ASSOCIATION STUDIES AND TEND NOT
TO LOOK AT IT AT ALL WHEN
CONDUCTING SYSTEMATIC REVIEWS.
IN THE AREA OF EVIDENCE-BASED
POLICY, THERE IS AN ALTERNATIVE
APPROACH CALLED THEORY-BASED
EVALUATION.
AND THIS ENCOMPASSES A RANGE OF
TECHNIQUES, INCLUDING REALIST
EVALUATION TECHNIQUES AND
CONTRIBUTION ANALYSIS.
THESE TECHNIQUES TEND TO FOCUS
ON THE RIGHT-HAND SIDE OF THE
PICTURE AT THE EXCLUSION OF THE
LEFT-HAND SIDE.
SO THEORY-BASED EVALUATION WAS
ORIGINALLY SUGGESTED BECAUSE OF
DISSATISFACTION WITH EBM AND
EBP, AND PUT FORWARD AS AN
ALTERNATIVE APPROACH THAT
FOCUSES ON MECHANISMS AND
DOESN'T LIKE TO PURSUE THE SORT
OF EXPERIMENTAL ASSOCIATION
STUDY OF EVIDENCE-BASED MEDICINE
AND EVIDENCE-BASED POLICY.
SO EVIDENTIAL PLURALISM CAN BE
THOUGHT OF AS COMBINING THE TECH
TECHNIQUES OF EVIDENCE-BASED
MEDICINE AND EVIDENCE-BASED
POLICY ON ONE HAND AND THEORY ON
THE OTHER, BUT INSTEAD OF
REJECTING THE OTHER TECHNIQUES,
TRYING TO BRING THEM TOGETHER IN
ORDER TO EVALUATE ASSOCIATION
STUDIES AND MECHANISTIC STUDIES
ALONGSIDE ONE ANOTHER.
IN THE SOCIAL SCIENCES, THERE'S
BEEN A BIG DEBATE AMONGST
RESEARCHERS AS TO WHETHER YOU
SHOULD USE QUANTITATIVE EVIDENCE
WHEN CONFIRMING YOUR CAUSAL
CLAIMS, OR TO QUALITATIVE
EVIDENCE/METHODS, AND RECENTLY,
IN RECENT YEARS, MIXED METHODS
RESEARCH HAS BEEN PUT FORWARD AS
AND SORT OF COMPROMISED WHERE
YOU APPEAL TO BOTH QUANTITATIVE
AND QUALITATIVE METHODS TO HELP
SUPPORT YOUR CONCLUSIONS.
EVIDENTIAL PLURALISM CAN BE
THOUGHT OF AS PROVIDING A
GENERAL SUPPORT FOR MIXED
METHODS RESEARCH, AND IT
CONCEDES OF MIXED METHODS
RESEARCH IN A CERTAIN SPECIFIC
WAY.
IT CONCEIVES OF QUANTITATIVE
METHODS AS BEING METHODS THAT
ARE TYPICALLY USED TO PRODUCE
ASSOCIATION STUDIES, AND IS
IMPORTANT INSOFAR AS THEY HAVE A
ROLE IN PRODUCING ASSOCIATION
STUDIES.
BUT IT ALSO RECOGNIZES THE NEED
FOR MECHANISTIC STUDIES AND
MECHANISTIC STUDIES CAN BE
EITHER QUANTITATIVE OR
QUALITATIVE, AND IN PARTICULAR
WHERE YOU DO HAVE HIGH QUALITY
QUALITATIVE RESEARCH IS VERY
IMPORTANT TO TAKE THAT INTO
ACCOUNT, BECAUSE HIGH QUALITY
QUALITATIVE RESEARCH CAN BE VERY
INFORMATIVE WITH RESPECT TO
FEATURES OF UNDERLYING
MECHANISMS.
SO EVIDENTIAL PLURALISM SAYS
THAT WE DO NEED TO TAKE BOTH
QUANTITATIVE AND QUALITATIVE
METHODS INTO ACCOUNT, AND THE
REASON WE NEED TO DO THIS IS
BECAUSE WE NEED TO FOCUS ON
ASSOCIATION STUDIES AND
MECHANISTIC STUDIES.
AND IT PROVIDES GUIDANCE AS TO
HOW TO INTEGRATE OUR
QUANTITATIVE AND QUALITATIVE
EVIDENCE.
WE STRUCTURE THIS INTEGRATION BY
PUTTING FORWARD SPECIFIC
MECHANISM HYPOTHESES, AND THEN
SEEING HOW QUANTITATIVE AND
QUALITATIVE STUDIES CONFIRM
THESE HYPOTHESES.
AND THAT FEEDS IN TO OUR
JUDGMENTS ABOUT CAUSATION.
CAUSAL MODELING TECHNIQUES CAN
ALSO BE VIEWED AS PART OF THIS
GENERAL PICTURE, SO MANY PEOPLE
ADVOCATE FORMAL METHODS FOR
CAUSAL MODELING SUCH AS
GRAPHICAL CAUSAL MODELS OR
STRUCTURAL EQUATION MODELS OR
MODELS THAT APPEAL TO
DIFFERENTIAL EQUATIONS, FOR
EXAMPLE.
THESE CAN BE VIEWED AS
FORMALISMS FOR PUTTING FORWARD
SPECIFIC MECHANISM HYPOTHESES.
SO THESE CONNECT THE PUTATIVE
CAUSE AND EFFECT TO INTERMEDIARY
VARIABLES, PERHAPS ALONG
MULTIPLE PATHWAYS.
AND CONFIRMING THESE MODELS CAN
HELP CONFIRM CAUSATION BECAUSE
THEY HELP TO TELL US THAT
THERE'S A MECHANISM LINKING THE
PUTATIVE CAUSE TO PUTATIVE
EFFECT.
SO THESE SORTS OF MODELING
TECHNIQUES CAN PLAY AN IMPORTANT
ROLE IN OUR CAUSAL INFERENCES.
OF COURSE ANY FORMALISM FOR
CAUSAL MODELING WILL MAKE STRONG
ASSUMPTIONS, AND THESE ALSO NEED
TO BE VALIDATED.
BUT ONCE THAT'S BORNE IN MIND,
THEY CAN PLAY A VERY USEFUL
ROLE.
OKAY, SO I HAVE PROVIDED A
GENERAL INTRODUCTION TO
EVIDENTIAL PLURALISM AND I'VE
TALKED A BIT ABOUT HOW IT RELATE
TO OTHER APPROACHES.
I'M NOW GOING TO MOVE ON TO THE
QUESTION OF EXTERNAL V VALIDITY
AND HOW IT CAPTURES
EXTRAPOLATING FROM ONE
POPULATION TO ANOTHER, AND THEN
WE'LL LOOK AT A SPECIFIC CASE
STUDY THAT SHOWS US HOW TO
EVALUATE EFFECTIVENESS USING
EVIDENTIAL PLURALISM.
SO NEXT UP, EXTERNAL VALIDITY,
HOW DO WE EXTRAPOLATE FROM ONE
POPULATION TO ANOTHER.
ACCORDING TO EVIDENTIAL
PLURALISM, IF YOU'VE GOT A
SOURCE POPULATION AND YOU CAN
ESTABLISH CAUSATION ON THE
SOURCE POPULATION, THEN THAT CAN
HELP CONFIRM YOUR CAUSAL CLAIM
ON THE TARGET POPULATION AS LONG
AS YOU CAN PROVIDE SOME EVIDENCE
THAT THE MECHANISMS OF ACTION ON
THE SOURCE POPULATION ARE
SIMILAR ENOUGH TO THE MECHANISMS
OF ACTION ON THE TARGET
POPULATION.
SO HERE YOU CAN THINK OF STUDIES
ON ONE COUNTRY AND WANTING TO
EXTRAPOLATE YOUR CAUSAL CLAIM TO
ANOTHER COUNTRY, OR YOU CAN
THINK OF, FOR EXAMPLE, STUDIES
OF MEDICINE ON MICE, AND YOU
WANT TO EXTRAPOLATE YOUR
CONCLUSIONS TO HELP CONFIRM
CAUSATION IN HUMANS.
NOW, TYPICALLY EVIDENCE-BASED
MEDICINE STRUGGLES TO PREHENCE
LIFL UNDERSTAND THE PROCESS OF
EXTRAPOLATION, AND THIS LEADS
MANY PROPONENTS OF
EVIDENCE-BASED MEDICINE TO BE
RATHER SKEPTICAL ABOUT THESE
SORTS OF EXTRAPOLATION
PROCESSES.
SHOULD WE BE USING ANIMAL
STUDIES AT ALL TO INFLUENCE OUR
JUDGMENTS OF CAUSATION IN HUM
HUMANS?
BUT THERE ARE CLEAR CASES WHERE
STUDIES ON ANIMALS CAN CONFIRM
CAUSATION IN HUMANS, AND THIS
APPROACH KNOWN IN THE
PHILOSOPHICAL LITERATURE IS
MECHANISM-BASED EXTRAPOLATION
HELPS US TO UNDERSTAND HOW
THAT'S POSSIBLE.
BECAUSE IF YOU CAN ESTABLISH
CAUSATION ON A SOURCE POPULATION
AND YOU KNOW THE MECHANISMS WORK
SIMILARLY IN THE TARGET
POPULATION, THEN THAT IS BOUND
TO CONFIRM CAUSATION ON THE
TARGET POPULATION.
AND YOU CAN COMBINE THIS APPEAL
TO SOURCE STUDIES, THAT IS,
STUDIES CARRIED OUT ON A
DIFFERENT SOURCE POPULATION,
WITH THE GENERAL PICTURE OF
EVIDENTIAL PLURALISM THAT
APPEALS TO ASSOCIATION STUDIES
AND MECHANISTIC STUDIES IN THE
TARGET POPULATION, AND YOU CAN
ENRICH THE PICTURE THAT
EVIDENTIAL PLURALISM PROVIDES BY
TAKING THESE SOURCE STUDIES INTO
ACCOUNT ALONGSIDE ASSOCIATION
STUDIES AND MECHANISTIC STUDIES.
AND TOGETHER, THEY CAN HELP
PROVIDE A SOLID BASIS FOR
JUDGMENTS ABOUT CAUSATION.
TO GIVE AN EXAMPLE OF AN
ORGANIZATION THAT DOES THIS VERY
WELL, I THINK, CONSIDER THE
INTERNATIONAL AGENCY FOR
RESEARCH ON CANCER.
SO IARC IS A WORLD HEALTH
ORGANIZATION BODY THAT EVALUATES
THE CARCINOGENICITY OF VARIOUS
SUBSTANCES OR ACTIVITIES THAT WE
MIGHT BE EXPOSED TO AS WORKERS
OR IN OUR DAILY LIFE.
HOW DO THEY ASSESS WHETHER AN
AGENT IS CARCINOGENIC IN HUMANS?
WELL, THEY HAVE SUBGROUPS OF
THEIR EVALUATION WORKING GROUP
THAT LOOK AT DIFFERENT KINDS OF
STUDIES.
SO ONE SUBGROUP FOCUSES
EXCLUSIVELY ON HUMAN
EPIDEMIOLOGICAL STUDIES, SO
STUDIES CARRIED OUT ON HUMANS
MEASURING EXPOSURE TO THE
POTENTIAL CARCINOGEN AND
OCCURRENCE OF CANCER.
SO THIS PLAYS THE ROLE OF
ASSOCIATION STUDIES IN THE
TARGET POPULATION.
ANOTHER SUBGROUP FOCUSES
ENTIRELY ON MECHANISTIC STUDIES
AND LOOKS TO SEE WHETHER KEY
FEATURES IN CANCER MECHANISMS
ARE PRESENT IN CASE OF EXPOSURE
TO THE AGENT IN QUESTION.
AND IARC HAVE A LIST OF 10 KEY
CHARACTERISTICS OF CANCER THAT
THEY USE TO STRUCTURE THIS PART
OF THE EVALUATION, AND THEY LOOK
TO SEE WHETHER -- WHICH OF THESE
10 FEATURES ARE PRESENT AND IF
SEVERAL OF THESE FEATURES ARE
PRESENT, THEN THAT CAN PROVIDE
STRONG EVIDENCE THAT THERE'S A
MECHANISM FROM THE AGENT TO
CANCER IN HUMANS.
A THIRD SUBGROUP OF THEIR
WORKING GROUP WILL LOOK AT
ANIMAL STUDY, MAYBE STUDIES
CARRIED OUT IN MICE OR RATS, FOR
EXAMPLE, AND AS LONG AS THERE'S
EVIDENCE OF SIMILARITY OF THE
UNDERLYING MECHANISMS, THIS WILL
HELP INFORM JUDGMENTS OF
CAUSATION.
THE OVERALL WORKING GROUP, WHEN
IT MEETS TOGETHER, WILL APPEAL
TO THESE ANIMAL STUDIES TO HELP
EVALUATE CARCINOGENICITY IN
HUMANS.
SO EVIDENTIAL PLURALISM PROVIDES
A NICE UNDERSTANDING OF HOW IARC
WORKS, AND IARC PROVIDES A NICE
PRACTICAL EXAMPLE OF HOW
EVIDENTIAL PLURALISM CAN WORK IN
PRACTICE.
SO IARC HAVE EVALUATED WELL OVER
A THOUSAND DIFFERENT AGENTS
USING THIS SORT OF APPROACH, AND
ITS CONCLUSIONS HAVE TURNED OUT
TO BE VERY ROBUST.
SO WE'VE GOT GOOD EVIDENCE THAT
EVIDENTIAL PLURALISM CAN WORK IN
PRACTICE.
ITS PRACTICABLE APPROACH.
AND WE CAN CARRY IT OUT IN A
SYSTEMATIC WAY.
IARC HAVE LOOKED AT A NUMBER OF
AGENTS IN A NUMBER OF CASES,
MECHANISTIC EVIDENCE HAS BEEN
ABSOLUTELY CRUCIAL TO HELPING TO
ASSESS CAUSATION.
SO FOR EXAMPLE, WITH SIMEON
VIRUS, THERE WAS ANIMAL
EVIDENCE, THERE WAS INADEQUATE
HUMAN EVIDENCE, BUT THERE WAS
EVIDENCE THAT THE MECHANISM OF
TRANSFORMATION IN THESE ANIMAL
STUDIES IS NOT OPERATING IN
HUMANS, SO THAT MECHANISM
EVIDENCE UNDER IT UNDERMINDING E
EXTRAPOLATION FROM ANIMALS TO
HUMANS.
THERE WAS ULTIMATELY NO GOOD
EVIDENCE OF CARCINOGENICITY.
IN MANY OTHER CASE WHERE THERE'S
BEEN ADEQUATE OR LIMITED
EVIDENCE IN HUMANS, THERE'S BEEN
STRONG EVIDENCE THAT SOME OF
THESE KEY CHARACTERISTICS OF
CANCER ARE PRESENT, SO THESE ARE
THE SPECIFIC MECHANISM
HYPOTHESES.
AND THESE HAVE HELPED LEAD TO
EVALUATIONS THAT CARCINOGENS ARE
PROBABLY CARCINOGENIC OR
POSSIBLY CARCINOGENIC IN HUMANS.
SO THEY HELP BOOST CONFIRMATION
IN CAUSATION.
TO CLOSE OFF, I'M GOING TO LOOK
NOW AT HOW WE WOULD EVALUATE
EFFECTIVENESS USING EVIDENTIAL
PLURALISM SO I'LL JUST RUN
THROUGH AN EXAMPLE.
THIS IS MOTIVATED BY SOME
DISCUSSION ABOUT THE ROLE OF
EVIDENCE-BASED MEDICINE IN THE
PANDEMIC.
SO SOME PEOPLE HAVE ARGUED THAT
EVIDENCE-BASED MEDICINE DIDN'T
PERFORM VERY WELL DURING THE
COVID PANDEMIC.
AND WE WOULD HAVE DONE BETTER
WITH EVIDENCE-BASED MEDICINE
PLUS.
SO GREENHALGH AND OTHERS HAVE
ARGUED, FOR EXAMPLE, THAT FOR
SOME ASPECTS OF THE PANDEMIC,
ESPECIALLY THOSE CHARACTERIZED
BY A COMBINATION OF COMPLEXITY,
URGENCY, AND THREAT, MECHANISTIC
EVIDENCE HAS BEEN
MISSION-CRITICAL AND RCTs
DIFFICULT OR IMPOSSIBLE.
THOUSANDS OF LIVES WERE LIKELY
LOST AS A RESULT OF WHAT WAS
INCORRECTLY CLAIMED TO BE AN
EVIDENCE-BASED APPROACH.
DISMISSING OR DOWNGRADING
MECHANISTIC EVIDENCE,
OVERVALUING FINDINGS FROM POORLY
DESIGNED OR IRRELEVANT RCTs,
AND ADVOCATING FOR INACTION
WHERE RCT EVIDENCE WAS LACKING.
THE PANDEMIC IS AN EP STE MIBG
OPPORTUNITY FOR THE EBM MOVEMENT
TO COME TO BETTER UNDERSTAND,
DEBATE AND EMBRACE EBM+.
SO HOW WOULD EBM+ WORK IN
PRACTICE IN THIS SORT OF HEALTH
SITUATION?
WELL, ONE APPROACH IS TO USE
STANDARD TECHNIQUES FOR
ASSESSING ASSOCIATION STUDIES TO
COME UP WITH A PRELIMINARY
CAUSATION, AND THEN IF THAT
PRELIMINARY EVALUATION FINDS
THAT CAUSATION ISN'T ESTABLISHED
AND THAT SPECIFIC MECHANISM
HYPOTHESES COULD MAKE A
DIFFERENCE TO THE OVERALL
JUDGMENT OF CAUSATION, THEN
SCRUTINIZE MECHANISTIC STUDIES
TO SEE WHETHER THEY CONFIRM OR
UNDERMINE JUDGMENTS OF CAUSAT
CAUSATION.
AND WE CAN DEVELOP A STEP-WISE
PROCEDURE FOR GOING THROUGH THIS
APPROACH.
FIRST SPECIFY THE CAUSAL CLAIM,
CORRELATION CLAIM, AND YOUR
SPECIFIC MECHANISM HYPOTHESES.
THEN YOU USE STANDARD TECHNIQUES
TO SEARCH FOR AND ASSESS
ASSOCIATION STUDIES.
YOU COME UP WITH A PRELIMINARY
EVALUATION, AND THIS WILL TELL
YOU WHETHER YOU NEED TO DO A
MECHANISTIC EVALUATION.
MOST CASES YOU WILL NEED TO
BECAUSE MECHANISM HYPOTHESES MAY
MAKE A DIFFERENCE TO THE OVERALL
JUDGMENTS.
IN THAT CASE YOU SUCH FOR
MECHANISTIC STUDIES, ASSESS
THOSE STUDIES AND THEN ASSESS
THE SPECIFIC MECHANISM
HYPOTHESES.
THEN YOU CAN REVISE YOUR
PRELIMINARY JUDGMENTS ABOUT
CORRELATION MECHANISM AND THE
CAUSAL CLAIM IN THE LIGHT OF
MECHANIC TIS EVIDENCE TAKEN
ALONGSIDE THE ASSOCIATION
STUDIES.
SO I'M GOING TO LOOK VERY
QUICKLY AT FACE MASK MANDATES TO
CONTROL COVID-19 AND HOW WE
MIGHT RUN THROUGH THE STEP WISE
PROCEDURE TO ASSESS FACE MASK
MANDATES.
THIS IS QUITE TOPICAL AT THE
MOMENT BECAUSE THERE'S RECENTLY
BEEN A VERY CONTROVERSIAL
COCHRANE REVIEW OF FACE MASKS.
THIS JUST LOOKED AT RCTs AND
HAD SEVERAL SIGNIFICANT
PROBLEMS.
IT DIDN'T FIND STRONG EFFECT
SIZE, BUT THE RCTs THAT IT
LOOKED AT HAD QUESTIONABLE
RELEVANCE, AND THE ANALYSIS IT
TOOK TO TRY AND ESTABLISH
CORRELATION WAS ALSO
CONTROVERSIAL.
SO WE'LL LOOK AND SEE HOW
EVIDENTIAL PLURALISM KEEPS WITH
THIS, AND THIS IS JOINT WORK
WITH MY COLLEAGUE ALEXANDRA
TROFIMOV.
WHAT ARE THE MECHANISM
HYPOTHESES HERE?
WELL, WE KNOW THAT COVID LEADS
TO A PREVALENCE OF COVID
INFECTIONS IN THE POPULATION BY
THREE MECHANISMS: AEROSOL,
DROPLET AND FOE MIGHT, AND THIS
LEADS TO COVID SYMPTOMS WHICH
CAN RESULT IN SEVERE DISEASE,
HOSPITALIZATION AND DEATH.
MASK REGULATIONS ARE
HYPOTHESIZED TO LEAD TO
WIDESPREAD MASK USAGE BY TWO
PATHWAYS.
ONE INVOLVING ENFORCEMENT AND
SANCTIONS, AND THE OTHER
ATTRIBUTABLE TO THE EXPRESS
SIEVE NATURE OF THE LAW, SHOWING
US WHAT WE OUGHT TO DO.
HYPOTHESIZED MECHANISM,
COUNTERACTING MECHANISM IS THAT
MASK USE MIGHT INCREASE THE
PREVALENCE OF COVID SYMPTOMS BY
REDUCING THE UPTAKE THE OTHER
PUBLIC HEALTH MEASURES, SO
THERE'S A WORRY THAT MAYBE IF WE
WEAR MASKS, WE'LL BE LESS LIKELY
TO TAKE UP OTHER PUBLIC HEALTH
INTERVENTIONS AND THAT MIGHT
COUNTERACT THE MECHANISM.
SO HOW ARE WE TO EVALUATE THIS?
FIRST WE HAVE TO SPECIFY THE
CAUSAL CLAIM, AND THIS IS THE
LEGAL MANDATE TO WEAR FACE
MASKS, REDUCE THE PREVALENCE OF
SYMPTOMATIC INFECTIONS.
WE ALSO NEED TO SPECIFY THE
CORRELATION CLAIM, AND THIS
INCLUDES LISTING POTENTIAL
CONFOUNDERS.
AND THEN WE NEED TO FORMULATE
SPECIFIC MECHANISM HYPOTHESES.
SO THERE'S THE MECHANISM OF
ACTION, THE LEGAL REQUIREMENT
INCREASES FACE MASK USE WHICH
REDUCES THE PREVALENCE OF COVID,
AND THEN HYPOTHESIZE
COUNTERACTING MECHANISM THAT
WEARING FACE MASKS WILL DECREASE
COMPLIANCE WITH OTHER PUBLIC
HEALTH MEASURES.
WE SEARCH FOR AND ASSESS
ASSOCIATION STUDIES, SO I'M NOT
GOING TO GO THROUGH THIS IN ANY
DETAIL BECAUSE THIS IS KIND OF
THE STANDARD APPROACH.
LOOKING AT ASSOCIATION STUDIES.
YOU FIND THAT ASSOCIATION
STUDIES TEND TO BE RELATIVELY
STRONG HERE IN LOOKING AT THE
EFFECTIVE -- PROVIDING STRONG
SUPPORT FOR THE EFFECTIVENESS OF
FACE MASK MANDATES.
AND PRELIMINARY DETERMINATION IS
THAT THE EVIDENCE FROM THESE
STUDIES ESTABLISHES THE
CORRELATION CLAIM BUT IT FALLS
SHORT OF ESTABLISH THE CAUSAL
CLAIM BECAUSE THERE MAY BE SOME
RESIDUAL CONFOUNDING THAT HASN'T
BEEN ADEQUATELY CONTROLLED FOR
BY THESE STUDIES.
SO THE CAUSAL CLAIM IS ONLY
PROVISIONALLY ESTABLISHED, AND
THE MECHANISTIC EVALUATION COULD
INCREASE CONFIDENCE IN THE
CAUSAL CLAIM.
SO WE DO NEED TO GO ON TO CARRY
OUT A MECHANISTIC EVALUATION
HERE.
SO WE SEARCH FOR AND ASSESS
MECHANISTIC STUDIES.
THERE'S TWO PARTS TO THE
MECHANISM OF ACTION.
THE FIRST PART IS DOES THE
MANDATE -- THE FACE MASK MANDATE
ACTUALLY LEAD TO COMPLIANCE, DO
WE USE FACE MASKS, AND HERE
THERE IS VERY GOOD SUPPORT FROM
STUDIES THAT THIS PART OF THE
MECHANISM EXISTS, BUT AGAIN,
IT'S NOT ENTIRELY CONCLUSIVE.
THE SECOND PART OF THE MECHANISM
HYPOTHESIS CONCERNS THE
EFFECTIVENESS OF FACE MASKS IN
REDUCING SYMPTOMATIC INFECTION,
SO GIVEN THAT WE USE FACE MASKS,
ARE THEY THEN EFFECTIVE AT
REDUCING SPREAD OF COVID-19.
AND SO WE SEARCH FOR AND ASSESS
STUDIES THERE TOO.
THE RECENT COCHRANE REVIEW
NEITHER SUPPORT NOR UNDERMINES
THE MECHANISM HYPOTHESIS BECAUSE
OF VARIOUS PROBLEMS WITH THE WAY
THE STUDY WAS CARRIED OUT.
WE THINK THAT THE FIRST PART OF
THE MECHANISM IS PROVISIONALLY
ESTABLISHED THAT MANDATES LEAD
TO WIDESPREAD USE OF FACE MASKS.
WHILE THE SECOND PART IS WELL
ESTABLISHED.
THERE'S VERY STRONG STUDIES WITH
RESPECT TO THE SECOND PART.
SO OVERALL, THE MECHANISM OF
ACTION IS PROVISIONALLY
ESTABLISHED.
THIS IS BECAUSE THE FIRST PART
IS ONLY PROVISIONALLY
ESTABLISHED.
THE COUNTERACTING MECHANISM HAS
BEEN COMPREHENSIVELY UNDERMINED
BY STUDIES IN THE LITERATURE.
AND THE VIEW IS THAT THE
CONTRACTING MECHANISM IS
ARGUABLY FALSE.
SO THEN WE NEED TO REVISE OUR
INITIAL JUDGMENT OF CORRELATION,
WHICH REMAINS ESTABLISHED, BUT
GIVEN CONCORDANT STRONG EVIDENCE
FROM ASSOCIATION STUDIES AND
MECHANISTIC STUDIES, WE
DETERMINE THAT THE GENERAL
MECHANISTIC CLAIM IS
ESTABLISHED.
AND SINCE BOTH CORRELATION AND
MECHANISM ARE ESTABLISHED, THE
CAUSAL CLAIM IS ALSO
ESTABLISHED.
SO THE PICTURE LOOKS LIKE THIS.
IT'S A BIT MORE COMPLICATED THAN
THE ONES WE'VE SEEN EARLIER.
THE ASSOCIATION STUDIES SUFFICE
ON THEIR OWN TO ESTABLISH
CORRELATION.
THEY PROVIDE SOME FAIRLY STRONG
SUPPORT FOR THE PRESENCE OF A
LINKING MECHANISM, BUT THEY
DON'T SUFFICE TO ESTABLISH A
MECHANISM.
THERE.
MECHANISTIC STUDIES PROVIDE
STRONG SUPPORT FOR MECHANISM
HYPOTHESES, WHICH END UP HAVING
BEEN PROVISIONALLY ESTABLISHED
AND ALSO PROVIDE STRONG SUPPORT
FOR THE LINKING MECHANISM.
BUT AGAIN, MECHANISTIC STUDIES
ON THEIR OWN DON'T SUFFICE TO
ESTABLISH THE MECHANISM CLAIM.
BUT TAKING THE STRONG SUPPORT
FROM THE ASSOCIATION STUDIES AND
THE MECHANISTIC STUDIES TOGET
TOGETHER, THE MECHANISM CLAIM
CAN ONLY BE VIEWED AS WELL
ESTABLISHED.
AND ONCE CORRELATION AND
MECHANISM ARE ESTABLISHED, SO,
TOO, IS CAUSATION ESTABLISHED.
SO JUST TO SUM UP THEN,
EVIDENTIAL PLURALISM PROVIDES AN
OVERARCHING FRAMEWORK FOR CAUSAL
INFERENCE.
THIS BRIDGES CLINICAL STUDIES,
EPIDEMIOLOGICAL STUDIES ON THE
ONE HAND WITH BASIC SCIENCE ON
THE OTHER AND THAT BASIC SCIENCE
IS THE PANDEMIC CLEARLY
SHOWS/INCLUDES BEHAVIORAL AND
SOCIAL SCIENCE.
EVIDENTIAL PLURALISM CAN BE
APPLIED TO BOTH MEDICINE AND
POLICY ASSESSMENT, AND CAN HELP
TO RESOLVE CONTROVERSIES SUCH AS
THE EFFECTIVENESS OF FACE MASK
MANDATES.
THANK YOU VERY MUCH.
>> THANK YOU SO MUCH, JON.
LET'S LEAVE THAT QR CODE UP FOR
A FEW MOMENTS SO OUR COLLEAGUES
CAN TAKE A PHOTO OR USE THEIR
CRAFTER FOR THAT.
I'LL START WITH THE QUESTIONS
THAT HAVE COME IN, AND MY
COLLEAGUE ON THIS TEAM --
[AUDIO DIFFICULTIES]
>> SORRY, BILL, I'VE LOST YOU.
>> -- WILL ALTERNATE.
I BEG YOUR PARD3?
PARDON?>> YOU CUT OUT.
>> I'M SORRY, IS THIS ANY
BETTER?
>> YES, THAT'S BETTER NOW.
>> OH, GOOD.
OUR BASIC SCIENTISTS HAVE --
[AUDIO DIFFICULTIES ?C]
STATED THEY'VE BEEN USING THE
EVIDENTIAL PLURALISM FOR YEARS,
BUT -- DO YOU RECOMMEND A GOOD
PLACE FOR THEM TO START?
TO LEARN MORE ABOUT HOW
EVIDENTIAL PLURALISM GOT ITS
START AND HOW THEY MIGHT BEGIN
TO INTEGRATE IT INTO THEIR OWN
WORK WHICH THEY SEE RELATES SO
CLOSELY TO YOURS?
>> I THINK THAT'S A VERY GOOD
QUESTION.
SO MY SUGGESTION IS TO HAVE A
LOOK AT LITERATURE ON EVIDENTIAL
PLURALISM THAT I LEFT UP THE
LINK TO AT THE END.
THAT INCLUDES THE TWO BOOKS,
EVIDENTIAL PLURALISM IN
MEDICINE, AND IN THE SOCIAL
SCIENCES.
IT'S CERTAINLY TRUE, ALTHOUGH --
SO THE STANDARD APPROACH IN
EVALUATION IS EVIDENCE-BASED
MEDICINE AND EVIDENCE-BASED
POLICY, AND THIS CONTRASTS QUITE
STRONGLY WITH EVIDENTIAL
PLURALISM.
BUT BASIC SCIENTISTS DO
NATURALLY THINK OFTEN IN TERMS
OF MECHANISMS ALONGSIDE
ASSOCIATIONS WHEN TRYING TO
ESTABLISH CAUSATION, AND
EVIDENTIAL PLURALISM CAN BE
VIEWED AS SOME KIND OF GENERAL
PHILOSOPHICAL UNDERPINNING FOR
THIS NATURAL WAY OF SEEING
THINGS.
SO IT CAN BE VIEWED AS PROVIDING
PHILOSOPHICAL FOUNDATIONS FOR
THIS APPROACH TO ASSESSING
CAUSATION.
AND A GENERAL OVERARCHING
FRAMEWORK WITHIN WHICH MANY WELL
DEVELOPED METHODS CAN FIT INTO.
SO FOR EXAMPLE, I MENTIONED
MIXED METHOD RESEARCH, WHICH HAS
BEEN STRONG FOR A LONG TIME.
EVIDENTIAL PLURALISM CAN BE
THOUGHT OF AS PROVIDING SOME
JUSTIFICATION FOR MIXED METHODS
RESEARCH THAT DIFFERS FROM OTHER
JUSTIFICATIONS THAT ARE AROUND
IN THE SOCIAL SCIENCES.
>> THANKS SO MUCH.
BECKY?
>> YES, THANK YOU.
I HAVE ANOTHER QUESTION FROM THE
AUDIENCE.
HOW DOES EBM HANDLE PUBLICATION
BIAS?
>> SO PUBLICATION BIAS IS USED
AS A WAY TO ASSESS QUALITY OF
ASSOCIATION STUDIES, STANDARDLY
BY EVIDENCE-BASED MEDICINE,
EVIDENCE-BASED POLICY, AND
EVIDENTIAL PLURALISM WOULD USE
THAT IN THE SAME WAY.
SO SOMETIMES WE CAN ASSESS THE
LIKELIHOOD OF PUBLICATION BIAS
IN A PARTICULAR AREA, AND DO
RISK OF BIAS ASSESSMENTS FOR
THESE ASSOCIATION STUDIES, AND
THE PRESENCE OF PUBLICATION BIAS
OFTEN LEADS US TO VIEW THE
ASSOCIATION STUDIES AS
INSUFFICIENT TO ESTABLISH
CAUSATION ON THEIR OWN.
SO THE PRESENCE OF PUBLICATION
BIAS LEADS TO THE FEED TO LOOK
AT MECHANISTIC EVIDENCE
ALONGSIDE ASSOCIATION STUDIES TO
SEE WHETHER WE CAN HELP TO
ESTABLISH CAUSATION.
PUBLICATION BIAS IS PERHAPS LESS
PROMINENT IN THE MECHANISTIC
LITERATURE THAN IN THE
LITERATURE, FOR EXAMPLE, ON
RANDOMIZED CONTROL TRIALS.
SO LOOKING AT MECHANISTIC
STUDIES CAN HELP PROVIDE AN
INDEPENDENT SOURCE OF EVIDENCE
THAT CAN BE USED TO BOOST OR
UNDERMINE JUDGMENTS OF
CAUSATION.
>> OUR NIH ASSOCIATE DIRECTOR
FOR BEHAVIORAL AND SOCIAL
SCIENCES HAD SOME TECHNICAL
DIFFICULTIES GETTING ON AT THE
BEGINNING, AS YOU KNOW, JON, AND
SO SHE'D LIKE TO COME ON AND ASK
HER OWN QUESTION ADG AND PROVIDU
HER SINCERE THANKS.
JANE?
>> OKAY.
I DIDN'T KNOW YOU WERE GOING TO
HAVE ME GO ON AT THE END.
I DON'T KNOW IF I'M IN A PLACE
WHERE YOU CAN HEAR ME VERY WELL
ACTUALLY.
BUT I'M SORRY WE COULDN'T GET
ON --
>> YOU SOUND GREAT.
>> OKAY.
FASCINATING TALK.
I'M LOOKING FORWARD TO LOOKING
AT THIS A LITTLE BIT IN MORE
DETAIL.
I DIDN'T HAVE A SPECIFIC
QUESTION BUT JUST WANTED TO
APOLOGIZE FOR NOT BEING ON AT
THE BEGINNING.
I'M SURE, BILL, YOU WERE ABLE TO
DO THE INTRODUCTION THEN?
>> THANK YOU VERY MUCH.
>> YES.
>> GREAT.
OKAY.
THANK YOU.
>> THANK YOU.
>> OH, YOU BET.
WE HAVE ONE MORE -- ANOTHER
QUESTION ABOUT FINDING PERHAPS
ATTEMPTS TO FIND CAUSALITY USING
YOUR APPROACHES IN A GREAT MANY
OF BEHAVIORAL INTERVENTIONS THAT
HAVE GONE ON OVER THE PAST 40,
50 YEARS.
IN PARTICULAR, THOSE THAT
HYPOTHESIZE THAT A CHANGE IN
SELF-EFFICACY CAN PREDICT
HEALTHIER BEHAVIOR, EITHER TO
CHANGE OR ADHERENCE IN THAT
REGARD.
THERE ARE MANY PUBLICATIONS,
HOWEVER, IN WHICH THAT ALL
HASN'T BEEN FOUND.
SOMETIMES SELF-EFFICACY
INCREASES, BUT NOT BEHAVIOR OR
THE REVERSE, AND GIVEN THE MANY
DIFFERENT WAYS YOU DEMONSTRATED
SO EARLY ON IN YOUR TALK, COULD
THE APPROACHES IN EVIDENTIAL
PLURALISM HELP TEASE OUT WHETHER
AND HOW THESE MECHANISMS WORK IN
OTHER WAYS OR WHAT OTHER ME CAN
MECHANISMS RESEARCHERS MIGHT
SEEK, STARTING WITH THE DATA
THAT THEY HAVE?
>> SO THAT'S AN INTERESTING
QUESTION.
I DON'T KNOW VERY MUCH ABOUT
THAT PARTICULAR AREA OF
BEHAVIORAL SCIENCE, SO I CAN'T
SAY TOO MUCH ABOUT IT, BUT I
WOULD SAY THAT OFTEN YOU DON'T
NEED TO KNOW VERY MUCH ABOUT
MECHANISMS TO PROVIDE BOOSTING
EVIDENCE FOR CAUSALITY.
SO YOU JUST NEED TO KNOW A FEW
INTERMEDIARY VARIABLES, FOR
EXAMPLE,, A FEW MEDIATING
VARIABLES, AND CONFIRMING THAT
THE SELF-EFFICACY CAN INFLUENCE
THESE INTERMEDIARY VARIABLES CAN
IN ITSELF PROVIDE STRONG SUPPORT
OF CAUSATION.
SO I JUST SAY THAT ALL IT TAKES
IS A FEW KEY MECHANISTIC
HYPOTHESES FOR, ONE, TO BE ABLE
TO USE EVIDENTIAL PLURALISM TO
HELP BOOST -- HELP CONFIRM OR
UNDERMINE CAUSATION.
SO PERHAPS IT MIGHT BE AN
APPROACH TO TRY TO SEE WHETHER
IT CAN HELP RESOLVE THIS
SITUATION IN THE LITERATURE
WHERE PEOPLE AREN'T SURE FROM
THE ASSOCIATION STUDIES ON THEIR
OWN WHETHER THERE IS CAUSATION
AND THE EXTENT TO WHICH THERE IS
CAUSATION.
THANK YOU.
>> LOVELY.
WHEN YOU WERE TALKING ABOUT THE
POWER OF PRAYER TO HELP PEOPLE
SHORTLY OUT OF HOSPITAL, IT
TRIGGERED A QUESTION FROM ONE OF
OUR COLLEAGUES WHO SAID THAT
THAT REMINDED HER OF THE MANY
DISCIPLINES THAT COMPRISE THE
HEALTH HUMANITIES.
MANY OF THE LEADERS OF THAT AREA
ARE IN THE U.K., THOUGH NOT ALL
OF THEM, AND MY COLLEAGUE
WONDERED IF HEALTH HUMANITIES --
IF YOUR APPROACHES ON CAUSALITY
MIGHT HELP THE HEALTH HUMANITIES
DEMONSTRATE CAUSALITY MORE
DIRECTLY FOR BASIC AND MEDICAL
PEOPLE, IF YOU'VE WORKED WITH
THOSE COLLEAGUES AT ALL AND
COULD SPEAK TO THIS.
I KNOW, AGAIN, THIS IS AN ASIDE
QUESTION.
>> YEAH, THANK YOU.
THAT'S AN INTERESTING QUESTION.
CERTAINLY CERTAIN APPROACHES IN
THE HEALTH HUMANITIES CAN FIT
INTO THIS FRAMEWORK QUITE WELL.
SO HEALTH HUMANITY TENDS TO
ADVOCATE FOCUSING STRONGLY ON
THE PATIENT'S PERSPECTIVE,
PATIENT NARRATIVES, AND SO ON,
AND THESE CAN REALLY BE VIEWED
AS PROVIDING GOOD INDICATORS OF
FEATURES OF MECHANISMS OF
DISEASE BUT ALSO MECHANISMS OF
TREATMENT THAT WORK AS WELL.
SO EVIDENTIAL PLURALISM TENDS TO
BE PRETTY OPEN TO THIS IDEA OF
USING ALL THE EVIDENCE THAT
YOU'VE GOT AVAILABLE TO HELP
INFORM YOUR JUDGMENTS OF
CAUSATION, AND THIS CAN INCLUDE
THE KINDS OF TREATMENTS OF
ILLNESS, DISEASE AND HEALTH
THAT'S AVAILABLE IN THE HEALTH
HUMANITIES, AS WELL AS THE
STANDARD LARGE STATISTICAL
TRIALS THAT PEOPLE ARE FAMILIAR
WITH IN THE MEDICAL ARENA.
SO IT WOULD DEFINITELY BE AN
INTERESTING AVENUE TO EXPLORE, I
THINK.
SO THANK YOU.
>> BRILLIANT, JON.
WE'RE COMING TO THE CLOSE OF OUR
HOUR, AND I WANTED TO BE
SENSITIVE OF EVERYONE'S TIME.
I ALSO WANT TO THANK YOU
IMMENSELY FROM ALL OF US AT NIH.
OUR OBSSR DIRECTOR JANE SIMONI,
JOSH GORDON, BECKY, THE CONCEPT
TEAM AND ALL THE PARTICIPANTS
FOR YOUR INTELLECT AND YOUR
TIME.
I HOPE THEY'VE TAKEN THE QR CODE
YOU SHOWED EARLIER.
I BROUGHT UP THIS SLIDE SO
FOLKS, IF THEY MISSED IT, CAN
TAKE A PHOTO OF YOUR PROFILE AT
U-KENT.
I COULDN'T HAVE ASKED, NONE OF
US COULD HAVE EXPECTED SUCH A
GREAT WAY TO BEGIN THIS SERIES,
AND WE LOOK FORWARD TO WORKING
WITH FUTURE SCHOLARS AND
BRINGING YOU BACK TO HELP US
DEVELOP THIS LINE OF WORK MORE
THOROUGHLY.
THANKS TO YOU ALL FOR WATCHING,
AND LOOK FOR MORE FROM US IN
THIS REGARD.
THANK YOU SO MUCH.
CHEERS.
THANK YOU ALL VERY MUCH FOR
COMING ALONG AND FOR HAVING ME
ON.
IT'S BEEN A GREAT PLEASURE.
THANKS.
THANK YOU SO MUCH, JON.
TAKE CARE.
>> BYE.