>> GOOD MORNING WELCOME BACK TO
THE NIDDK WORKSHOP LEVERAGING
EVIDENCE TO ASSESS BENEFITS AND
GLP-1-BASED THERAPIES. THIS
MORNING BEGINS WITH SESSION 4 ON
BEST PRACTICES FOR STUDIES GLP-1
THERAPIES. WE WILL BREAK FOR
LUNCH AT 12:35 UNTIL 1:15 P.M.
EASTERN TIME AND AFTER THE LUNCH
WORKSHOP WILL CONTINUE AND
SUMMARIZE RESEARCH GAPS AND
OPPORTUNITIES AND LEAD A
DISCUSSION WITH WORKSHOP
ATTENDEES LAND ADJOURN AT 2
O'CLOCK PM EASTERN TIME. BEFORE
WE GET STARTED I WOULD LIKE TO
REVIEW SOME HOUSEKEEPING ITEMS.
THE MEETING IS BEING RECORDED
AND WILL BE POSTED TO NIH
WEBSITE AND JOHN FROM SCIENTIFIC
CONSULTING GROUP OR SCG IS THE
MEETING HOST. E-MAIL HER AT
DJONIGAN WITH ANY TECHNICAL
ISSUES AND USE THE Q & A
FUNCTION TO ASK QUESTIONS OF
SPEAKERS AT ANY TIME. ATTENDEES
CAN UPVOTE QUESTIONS IN THE Q &
A.
THE CHAT IS DISABLED FOR THE
WORKSHOP AND RAISED HAND FEATURE
WILL NOT BE USED. PLEASE USE
THE Q & A FUNCTION INSTEAD. I
WOULD LIKE TO WELCOME KATHLEEN
MCTEEING MODERATOR FOR SESSION
4, BEST PRACTICES FOR STUDYING
GLP-1-BASED THERAPIES DEFINING
EXPOSURE AND OUTCOMES.
DR. MATIG?
>> THANK SO YOU MUCH. I'M
DELIGHTED TO INTRODUCE OUR FIRST
SPEAKER THIS MORNING. A.
RESEARCH FOCUSES ON IDENTIFYING
SCALEABLE AND TRANSLATABLE
METHODS PREVENTING AND TREATING
OBESITY WITH EMPHASIS LEVERAGING
REAL WORLD DATA SETS
PARTICULARLY HEALTH CARE
PATTERNS.
DR. LOUIS WILL DISCUSS DEFINING
EXPOSURES TO GLP-1-BASED
THERAPIES AND COMPARISON GROUPS
USING REAL WORLD DATA AND
REMINDER TO PUT Q & A QUESTIONS
IN THE PANEL AND WE WILL
DISCUSSION THEM AFTER THE
PRESENTATION. DR. LOUIS.
>> ALL RIGHT. LET ME GET MY
SCREENS PULLED UP FOR YOU GUYS.
HOPEFULLY YOU ARE SEEING AND
HEARING.
GOOD MORNING, EVERYBODY. AND
THANK YOU FOR COMING BACK FOR
ROUND 2. SO MANY GREAT TALKS
YESTERDAY. I'M EXCITED TO
HOPEFULLY BUILD ON SOME OF THE
CONCEPTS AND MAYBE PRESENT THEM
IN A SLIGHTLY DIFFERENT LIGHT
THINKING ABOUT METHODS WE WANT
TO USE WHEN WE ARE USING
REAL-WORLD DATA SETS TO COMPARE
OUTCOMES AFTER GLP-1 THERAPIES
AND HOPING IN PARTICULAR YOU ARE
ABLE TO CATCH BEFORE RENANS TALK
YESTERDAY ON TRIALS. LOTS OF
CONKROEPTS I WILL COVER WILL
REFLECT STEPS OR DESIGN CHOICES
A RESEARCH MIGHT MAKE IN THAT
PROCESS. AS A DISCLAIMER, I
WOMAN TO THE AREA OF RESEARCH IN
BACKGROUND IN CLINICAL OBESITY
MANY ED CIN AND HEALTH RESEARCH
AND NOT A
PHARMACOEPIDEMIOLOGISTS BY
TRAINING AND MY HOPE IS FOR
THOSE IN THE AUDIENCE WITH A
CLINICAL BACKGROUND, THIS
LECTURE CAN HELP TO WALK YOU
THROUGH VERY BASIC CONCEPTS IN
PHARMACOEPITHAT WILL IMPROVE
INTERNAL VALIDITY OF YOUR
REAL-WORLD STUDIES OF GLP-1
MEDICATIONS.
THESE ARE MY DISCLOSURES.
I GUESS, FIRST, YOU KNOW, WE SAW
LOTS OF DATA PRESENTED YESTERDAY
THAT SHOWS US THE ENORMOUS
UPTAKE AND INTEREST IN THESE
MEDICATIONS IN THE UNITED STATES
AND AROUND THE WORLD ARE
MILLIONS OF PEOPLE THAT HAVE
BEEN EXPOSED TO GLP-1
MEDICATIONS AND THINK IT IS
IMPORTANT AS WE THINK ABOUT THE
NUMBER OF PEOPLE THAT CAN
POTENTIALLY COME INTO OUR
STUDIES THAT WE ARE VERY
THOUGHTFUL ABOUT WHO MAKES IT
INTO OUR STUDY COHORTS USING
REAL WORLD DATA SETS.
FOR MANY RESEARCH QUESTIONS
SEEKING TO ESTABLISH A CAUSAL
LINK BETWEEN STARTING A GLP-1
AND A POSITIVE HEALTH OUTCOME OR
ADVERSE HEALTH OUTCOME IT WILL
BE OPTIMAL IN MOST CASES TO
SELECT PEOPLE TAKING A MANY
EDUCATION FOR A FIRST TIME
INCIDENT OR NEW USERS AND WHY DO
WE WANT TO DO THIS? SELECTING
FIRST-TIME USERS WILL GIVE US
MORE CONFIDENCE THAT OUR
BASELINE AND PRE-TREATMENT
CHARACTERISTICS ARE BEING
MEASURED IN ADVANCE TO EXPOSURE
OF THING WE ARE TRYING TO STUDY
GLP-1 AND SOMEONE BEING ON A
GLP-1 IN PAST YEAR MIGHT HAVE A
CURRENT BMI OF 30 BUT COULD BE
DOWN FROM BMI OF 35 AND IS
PHYSIOLOGICALLY A DIFFERENT
PATIENT THAN PERSON STARTING OUT
IN BMI OF 30 AND INITIATING
GLP-1 AND INITIALLY PREVALENT
USERS OF MEDICATION ARE INCLUDED
ALONGSIDE BRAND NEW USERS IT
WILL RISK US NOT GETTING A REAL
TRUE SENSE OF THE TOLLRABILITY
OF THESE MEDICATIONS.
PREVALENT USERS ARE PEOPLE
PROBABLY THAT DIDN'T HAVE SUPER
HORRIBLE OR REACTIONS OR SERIOUS
ADVERSE REACTION AND CAN RESTART
THE MEDICATION OR RESTART IT
SAFELY AFTER A BREAK AND
OPERATIONALIZING THIS IDEA
IMAGINE WE HAVE AN E HAD. R
DATA SET AND WANT TO LOOK AT
WEIGHTELOUS OUTCOMES FOR
PATIENTS ON SEW MAKING LA TIED
AND -- .25 MILLIGRAMS IN FIRST
MONTH DATA SAYING THESE ARE
PEOPLE STARTING OUT AND PLAN TO
FOLLOW INDIVIDUALS FOR 12 MONTHS
WE WOULD PROBABLY CAPTURE NEW
USERS OF MEDICATION WITH THIS
APPROACH BUT WOULD ALSO MIX IN A
LOT OF PEOPLE WHO HAD BEEN
TAKING THE MEDICINE PREVIOUSLY
AND CONTINUED BECAUSE IT WAS
WORKING WELL FOR THEM OR
RESUMING AFTER A PAUSE TAKEN FOR
SOME OTHER REASON.
HOW DO WE GO ABOUT FINDING
INCIDENT USERS OF GLP-1
MEDICATIONS? IN REAL-WORLD
DATASETS WE WILL HAVE ACCESS TO
CALENDAR TIME PERIOD WORTH OF
DATA AND IMAGINE 2020 TO 2024
AND LOOKING AT PEOPLE WITH FIRST
PRESCRIPTION OFSOME AGO LA TIED
IN DATA WE WON'T BE SURE WHETHER
THAT IS FIRST TIME WE ARE
GETTING MEDICINE OR FIRST TIME
WE CAN SEE IT IN OUR DATA SET.
WE DON'T HAVE INFORMATION PRIOR
TO 20 TWENTD AND FOR THIS REASON
WE NEED A LOOK-BACK PERIOD OR
WASH OUT AND SOME TIME BEFORE WE
CALL START DATE OFSOME AGO LA
TIED FOR EACH PERSON SCANNING
BACK OVER TIME AND DOUBLE
CHECKING THEY WEREN'T PREVIOUSLY
PRESCRIBED THIS MED KRAGS.
APPLYING A WASHOUT ADDS ANOTHER
LAYER FOR INCLUSION FOR STUDY.
NOT ONLY DOES PERSON HAVE TO
HAVE FIRST PRESCRIPTION FORSOME
AGO LOW TIDE.
>> SEM AGO LA AGLUTIDE -- LIMIT
A SMALLER POOL OF PEOPLE WITH
THAT MUCH PREPRESCRIPTION DATA
AVAILABLE TO LOOK AT. CONVERSE
OF THESE THINGS WILL BE TRUE
WITH A LONGER WASHOUT. HOW LONG
IS IDEAL OR ADEQUATE FOR A
WASHOUT? THERE HAVE BEEN REALLY
NICE STUDIES LOOKING AT THIS
WITH OTHER MEDICATIONS FOR
CHRONIC CONDITIONS THAT SUGGESTS
THAT SORT OF STANDARD SIX MONTHS
WE USE IN MANY STUDIES IS
PROBABLY THE BEAR MINIMUM AROUND
AT RISK FOR LOTS OF
MISCLASSIFICATION AND IDEALLY IF
SAMPLE SIZE AND DATA CAN SUPPORT
IT LOOKING BACK 12 TO 24 MONTHS
MAKES MORE SENSE AND MAKES SENSE
TO DO IT IN A FEW DIFFERENT WAYS
AND USING LESS STRINGENT
12-MONTH WASHOUT FOR MAIN
ANALYSIS ON LARGEST SAMPLE AND
DOG SENSITIVITY ANALYSIS TO SEE
HOW RESULTS CHANGE IF YOU
RESTRICT TO PEOPLE WITH TRUE
INCIDENT USE USING A 24-MONTH
WASHOUT AND MAKING IT EASIER FOR
GLP-1S COMPARED TO OLDER OAMS
AND MANY DRUGS IS MOST CAME TO
MARKET AND DATA EXPANDING BEFORE
TIME OF FDA APPROVAL YOU CAN BE
PRETTY CONFIDENT YOU ARE NOT
MISSING ANY PREVALENT USERS
BEFORE THAT DATE.
ANOTHER IMPORTANT CONSIDERATION
WHEN WE ARE CONDUCTING RESEARCH
ON GLP-1S IS TRYING TO TEASE OUT
THE REASON THAT SOMEBODY IS
USING THE MEDICATION THAT CAN
HAVE REALLY IMPORTANT
IMPLICATIONS FOR INTERPRETING
EFFECTIVENESS AT SAFETY SIGNALS.
THIS WAS DISCUSSED A LOT
YESTERDAY. I THINK ONE OF THE
REASONS THIS CLASS OF MEDICINES
IS SO EXCITING IS THAT UNLIKE
OTHER MEDICINES USED FOR OBESITY
OR DIABETES, GLP-1S HAVE
MULTIPLE LABELED AND EMERGING
OFF-LABEL USES FOR WHICH DOCTORS
ARE PRESCRIBING THEM AND AS WE
USE CLINICAL DATA TO STUDY MEDS
THOUGH, IT IS IMPORTANT FOR US
TO TRY TO UNDERSTAND THE REASON
WHY SOMEONE IS TAKING A GLP-1
BECAUSE OF THE RISK OF
CONFOUNDING BY INDICATION OR
CONTRAINDICATION.
OUTCOMES OF INTEREST SUCH AS
WEIGHT LOSS TALKING ABOUT
OBESITY COULD BE DIFFERENT
DEPENDING ON POPULATIONS OF
PATIENTS DEPENDING WHY THEY ARE
TAKING THE MEDICINE AND FOR
EXAMPLE IF YOU WANT TO COMPARE
WEIGHT LOSS FOR PATIENTS TAKING
SEMAGLUTIDE IT IS IMPORTANT THAT
YOU KNOW THAT 100% OF SAMPLE OF
USERS WILL TAKE THAT MEDICATION
FOR WEIGHT LOSS AND IS THE ONLY
INDICATION FOR THAT DRUG. WHILE
IF NOT CAREFUL -- DIABETES
TREATMENT NOT WEIGHT LOSS AND
PATIENTS WITH DIABETES HAVE
DIFFERENT BEHAVIOR AND CARE
PATTERNS AND DIFFERENT
PHYSIOLOGY THAT IMPACT
EFFECTIVENESS OF SEMAGLUTIDE FOR
WEIGHT LOSS YOU HAVE COMPARISON
WITH UNMEASURED CONFOUNDING BY
MEDICATION AND HOW DOES IT PLAY
INTO THE REAL-WORLD DATA AND
THIS STUDY WAS CITED SOME
YESTERDAY AND IS A GROUP THAT
HAS DONE PUBLISHING LOOKING AT
EARLY OUTCOMES WITH GLP-1S AND
REAL WORLD DATA SETS AND THIS
TABLE SHOWS WHERE WHEN THEY LOOK
AT WEIGHT LOSS ACROSS
INDICATIONS ACCORDING TO BRAND
NAME THE PRESENCE OF TYPE 2
DIABETES DIAGNOSIS, YOU CAN SEE
HERE THE PROPORTION OF PATIENTS
IN THIS STUDY WHO WERE ABLE TO
ACHIEVE 10% WEIGHT LOSS BY ONE
YEAR AFTER TREATMENT INITIATION
WAS NEARLY DOUBLED AMONG THOSE
APPEARING TO TAKE MEDICATION FOR
BEAU BE
-- OBESITY AND TYPE 2 DIABETES
IS LOWER THAN WHAT WE WOULD SEE
IN A CLINICAL TRIAL AND SAMPLE
SIZES HERE YOU CAN SEE FAR FEWER
PATIENTS MAKING IT INTO GROUPS
OF TAKING THIS MEDICINE FOR
OBESITY.
HOW DO WE GO ABOUT FIGURING OUT
THE INDICATION WHEN WE DON'T
NECESSARILY WE WEREN'T THERE IN
THE ROOM AND DON'T KNOW
CONVERSATION BETWEEN CLINICIAN
AND PATIENT AND A COUPLE
DIFFERENT WAYS TO THINK ABOUT
DOING THIS IF YOU ARE REALLY
WANTING TO UNDERSTAND GLP-1 AS
TREATMENT FOR OBESITY A STRICT
WAY TO IDENTIFY PATIENTS MIGHT
BE TO RESTRICT TO PEOPLE THAT
DON'T HAVE EVIDENCE OF TYPE 2
DIABETES IN ENTIRE TREATMENT
BASELINE PERIOD AND ONLY REALLY
LOOK AT PEOPLE TAKING THE
VERSION OF THE MEDICINE LABELED
FOR OBESITY AND FOR SEMAGLUTIDE
USING [INDISCERNIBLE] AND OSDEM
PICK AND MAKING SURE PATIENT
MEETS CRITERIA AND PATIENT IS
ELIGIBLE FOR OBESITY TREATMENT
AT BASELINE BMI MEASURE OR
OBESITY DIAGNOSIS AND UPSIDE OF
TAKING STRICTER APPROACH TO
DEFINING INDICATION WOULD
INCLUDE REDUCING RISK OF
CONFOUNDING AND PROBABLY
PRODUCING A MORE ACCURATE
ESTIMATE OF TREATMENT EFFECTS
FOR POPULATION YOU ARE
INTERESTED IN GENERALIZING TO.
DOWNSIDES YOU WILL END UP WITH
SMALLER SAMPLE SIZE FOR BEING
STRICT AND OBESITY TREATMENT IN
PARTICULAR SHORTER FOLLOW UP
TIME NOW GIVEN RELATIVELY RECENT
FDA APPROVAL OF VERSIONS OF MEDS
RELATIVE TO DIABETES VERSIONS.
BECAUSE OF THE DIFFICULTIES
INHERIENT IN STRICTLY
IDENTIFYING PATIENTS USING
GLP-1S AND OBESITY AND BECAUSE
OF LARGE AMOUNT OF OFF LABEL USE
OF DIABETES MEDICINES FOR
PURPOSE IT MIGHT MAKE MORE SENSE
FOR CURRENT DATASETS TO TAKE A
LITTLE LESS STRICT APPROACH TO
CREATE LARGER AND MORE
GENERALIZABLE COHORTS AND HERE
YOU CAN THINK OF LIMITING
COHORTS TO PEOPLE TAKING ONE OF
GLP-1 MEDICATIONS WHO DON'T
APPEAR TO HAVE EVIDENCE OF
DIABETES IN PRETROO EMENT
BASELINE PERIOD LAND ALLOW YOU
TO CAPTURE MORE FOLKS EXPOSED TO
MEDICATION SOONER AND MAKING
SENSE GIVEN TREATMENT
ENVIRONMENT OF THE LAST FEW
YEARS.
WHEN WE ARE TRYING TO UNDERSTAND
THE HEALTH AND SAFETY
IMPLICATIONS OF THESE
MEDICATIONS, IT IS ALSO REALLY,
REALLY IMPORTANT AS WE DESIGN
THESE STUDIES TO THINK CAREFULLY
ABOUT THE CHOICE OF COMPARISON
GROUP.
ONE OPTION THAT IS PRETTY
APPEALING IS TO TAKE PATIENTS
WHO ARE GIVEN A GLP-1 MEDICINE
COMPARING TO GROUP OF PATIENTS
WITH MEDICATION WHETHER OBOO
ESTY AND DIABETES AND THOSE THAT
ARE NOT TREATED WITH
PHARMACOTHERAPY AT ALL THIS
COULD BE A NEW USER OF GLP-1
VERSUS A NONUSER DESIGN. IN
THEORY THIS DESIGN IS APPEALING
SIMILAR TO PHASE 3 PLACEBO
CONTROL TRIAL AND NONCARE IS
PHARMACOLOGICAL INTERVENTION AND
OBESITY ASSUME CARE OF LIFESTYLE
ADVICE AND IN THIS DESIGN WE
SEEK TO ANSWER QUESTION IS IT
BETTER TO TREAT WITH THIS DRUG
OR NOT TREAT AT ALL WITH A DRUG?
IN THIS DESIGN WE IDENTIFY A
GROUP OF INCIDENT USERS WITH
SEMAGLUTIDE AND COMPARE THEM TO
GROUP OF PEOPLE NOT TAKING
MEDICINE FOR OBESITY AND ARE
SIMILAR -- ALTHOUGH THIS IS
APPEALING IN A NUMBER OF
SETTINGS THAT IS IMPORTANT TO
THINK ABOUT HOW THIS APPROACH
MIGHT LEAD TO INACCURATE
ESTIMATES OF DRUG SAFETY AND
EFFECTIVENESS AND -- AS HE NOTED
A NUMBER OF OBSERVATIONAL
STUDIES AND IDENTIFIED SIZABLE
AND RELATIVELY RAPID IMPACTS OF
BERI AT TRICK SURGERY ON
CARDIOVASCULAR ENDPOINTS WITH
50% REDUCTION IN MACE RISK AND
THAT WAS A NICE PAPER PUBLISHED
A COUPLE YEARS AGO AND
HYPOTHESIZED THAT USE OF
UNTREATED CONTROLS WAS
CONFOUNDED IN SURGERY STUDIES
AND TYPE OF PATIENT SELECTED
BERI AT TRICK SURGERY AND
UNDERGOES IT -- BARI AT TRATRIC
ASSOCIATED WITH ABILITY TO
UNDERGO ELECTRICAL SURGERY LIKE
BERI AT TRICK SURGERY AROUND
COMPARISON GROUP OF PATIENTS
WITH OBESITY UNDERGOING ELECTIVE
JOINT REPLACEMENT SURGERY AND
NOT AN OBESITY TREATMENT AND
NONETHELESS ELECTIVE PROCEDURE
THAT PEOPLE WITH OBESITY HAVE
AND SHOULDN'T HAVE DIRECT IMPACT
ON OUTCOME OF CVD.
YET THE WEIGHT LOSS AND DIABETES
BENEFITS OF BERI AT TRICK
SURGERY WERE MAINTAINED IN
ANALYSIS AND I KNOW THERE HAVE
BEEN CRITIQUES OF THE PAPER IN
TERMS OF SELECTION OF JOINT
REPLACED SURGERY INAPPROPRIATE
COMPARISON GROUP AND THINK IT IS
AN IMPORTANT DEMONSTRATION OF
THE IMPACT THAT OUR COMPARATOR
GROUP HAS ON OUTCOMES LIKELY
HIGHLY CORRELATED WITH FACTORS
THAT RELATE TO TREATMENT
ENGAGEMENT.
ANOTHER ISSUE FOR RESEARCHERS TO
BE CAREFUL ABOUT WITH UNTREATED
CONTROL WAS THAT OF IMMORTAL
TIME BIAS AND IMAGINE A STUDY WE
WANT TO UNDERSTAND ALL CAUSE
MORTALITY WITH ADULTS WITH KNOWN
CARDIOVASCULAR DISEASE AND FOR
THIS STUDY WE WOULD PROBABLY
IDENTIFY PEOPLE WITH KNOWN CBD
WHO ARE STARTED ONSOME AGO LA
TIED AND WE START TO FOLLOW THEM
FORWARD LOOKING FOR OUTCOME OF
DEATH AND UNTREATED COMPARISON
GROUP HERE WE IDENTIFY PEOPLE
WITH CARDIOVASCULAR DISEASE AND
CLAIMS AND EHR FOLLOWING FIRST
TIME WE SEE CEB EVENT FOLLOWING
CLAIMS IN FOLLOW UP GROUP AND
FOLLOWING THEM FORWARD LOOKING
AT OUTCOME TIME OF DEATH AND
GIVEN THIS APPROACH WE GIVE
SEMAGLUTIDE GROUP AN AHEAD HERE
AND IN THE PAST THEY HAD CVD
EVENT AND SURVIVED IT LONG
ENOUGH AND DID WELL ENOUGH
SOMEONE THOUGHT THEY SHOULD BE
STARTED ON SEMAGLUTIDE AND
STARTING SEMAGLUTIDE IS EXCLUDED
FROM ANALYSIS APPROACH AND
WITHIN IT IS DEATHS OF PEOPLE
THAT DIDN'T MAKE IT OR WEREN'T
WELL ENOUGH AND WILL BE CAPTURED
IN UNTREATED CONTROLS.
SO OUR SEMAGLUTIDE USERS ARE IN
A SENSE SOMEWHAT IMMORTAL
COMPARED TO NONUSER CVD CONTROLS
LEADING TO OVERESTIMATE OF
SEMAGLUTIDE FOR ALL CAUSE IN
THIS GROUP AND NUMBER OF COOL
DESIGN -- I WON'T COVER THEM
TODAY. I WILL PROVIDE YOU
REFERENCES AT THE END OF THIS IF
YOU WANT TO GO BACK AND DO MORE
READING AND LEARN MORE.
RATHER THAN COMPARING GLP-1
TREATED PATIENTS TO UNTREATED
CONTROLS BETTER STRATEGY IN MOST
CASES IS SELECTING ACTIVE
COMPARATORS AND PEOPLE GETTING
SOME OTHER KIND OF TREATMENT FOR
CONDITION UNDER STUDY AND IN
THIS CASE BECAUSE BOTH GROUPS
ARE PEOPLE WHO ARE PRESUMABLY
BOTH SEEKING AND RECEIVING
TREATMENT THAT I THINK RECEIVING
TREATMENT PIECE IS CRITICAL HERE
FOR OBESITY AND THEY ARE MORE
LIKELY TO BE SIMILAR ON A NUMBER
OF IMPORTANT CHARACTERISTICS AND
SOME OF THE CHARACTERISTICS ARE
THINGS EASY TO MEASURE AND MATCH
AND ADJUST FOR ANYWAY.
OTHER OF THE CHARACTERISTICS
MIGHT NOT BE EASILY MEASURABLE
IN REAL-WORLD DATA SETS AND IS
NICE TO HAVE THIS INTANGIBLES
AND BACKINTANGIBLES THAT ARE
LIKELY BALANCED AS WELL IN THESE
GROUPS AND ANOTHER CLEAR BENEFIT
HERE IS IF YOU HAVE TWO ACTIVELY
TREATED GROUPS CAN YOU ASSIGN A
CLEAR TIME 0 FOR START DATA
TREATMENT TO BOTH GROUPS
REDUCING RISK OF IMMORTAL TIME
BIAS AND IT IS IMPORTANT TO
CHOOSE YOUR COMPARISON GROUP
CAREFULLY TO CONSIDER HOW YOU
CAN BALANCE GROUPS ON MEASURES
INTRODUCING INDICATION AND
CONTRAINDICATION AND DR. HER AND
INS TALK YESTERDAY AS A
CLINICIAN ASK YOURSELF IS IT
GOING TO ANSWER AN IMPORTANT
CLINICAL OR POLICY QUESTION TO
RANDOMIZE THIS GROUP OF PATIENTS
TO EACH OF THE TWO TREATMENTS
AND IS IT SOMETHING THAT MAKES
SENSE TO DO AND IF NOT DON'T
PURSUE THE QUESTION MAYBE.
WHAT TYPE OF ACTIVE COMPARATOR
WOULD WE PICK IN STUDIES OF
GLP-1S AND REALLY NICE ONE THAT
ANSWERS A PERTINENT QUESTION IF
YOU HAVE A PATIENT CONSIDERING
GLP1 WHICH SHOULD YOU PUT THEM
ON? IS THERE ONE BETTER THAN
THE OTHER? FOR EXAMPLE.
COMPARING WHAT HAPPENS TO
PATIENTS WHO ARE PLACED ON GLP-1
VERSUS MEDICATIONS FROM A
DIFFERENT CLASS; RIGHT?
THIS IS A DECISION WE MAKE A LOT
IN CLINICAL PRACTICE AND IN THE
TYPES OF COMPARISONS YOU HAVE TO
BE CAREFUL FOR CONFOUNDING BY
INDICATION AND CONTRAINDICATION
AND IMAGINE LOOKING AT
CARDIOVASCULAR OUTCOMES AND
PATIENTS PRESCRIBED FENTER MEAN
VERSUS GLP-1 FENTER MEAN IS THIN
ON THOSE PEOPLE WITH
CARDIOVASCULAR RISK PEOPLE WON'T
BE PRESCRIBED THAT MEDICATION IF
THEY HAVE CARDIOVASCULAR RISK
AND PAYING ATTENTION TO THAT.
MOST NONGLP-1 OBESITY MEDICINES
ARE A FEW YEARS OLDER OR BEEN ON
MARKET OLDER AND -- OLDER DRUG
USERS MAY ACTUALLY BE PREVALENT
USE
USERS.
ONE THING I LIKE ABOUT THIS FOR
NEWER POTENT DRUGS AND YOU WANT
A COMPARISON GROUP WITH
COMPAR
COMPARABLE WEIGHT LOSS THIS IS
APPEALING AND IS IMPORTANT TO
REMEMBER AND BROUGHT UP
YESTERDAY BARIATRIC PATIENTS
HAVE TO GO THROUGH ENORMOUS
PRESCREENING PROCESS AND FOLKS
MAKING IT TO BARIATRIC SURGERY
ARE LESS LIKELY TO HAVE
PRE-EXISTING CANCER AT TIME THEY
HAVE SURGERY AND ARE LESS LIKELY
TO HAVE ACTIVE SEVERE MENTAL
ILLNESS AND CARDIOVASCULAR
DISEASE AND LOOKING FOR OUTCOMES
IN FIRST FEW YEARS AFTER SURGERY
VERSUS STARTING IN AOM BARAT
TRICK PATIENTS WILL BE LESS
LIKELY TO HAVE THEM BASED ON
VIRTUE OF PRESCREENING AND ONCE
YOU HAVE IDENTIFIED YOUR TREATED
POPULATION AND COMPARISON GROUP
AND HAVE A STARTING POINT FOR
EVERY PATIENT IN YOUR STUDY
ANOTHER IMPORTANT CONSIDERATION
FOR YOU WITH REAL WORLD DATA
WILL BE HOW DO YOU FOLLOW PEOPLE
FORWARD AND ANALYZE THEIR DATA
OVER OBSERVABLE FOLLOW UP TIME
AND THIS DIRECTION IS LINKED TO
YOUR PLANS FOR ANALYSIS OF THAT
OUTCOME DATA CONSIDERING TARGET
TRIAL -- INTENTION TO TREAT
ANALYSIS IN MIND AND APPLYING
THIS LOGIC TO AN OBSERVATIONAL
STUDY OF GLP-1 AND USING
INSURANCE CLAIMS DATA THAT I
WORK WITH A LOT WE MIGHT HAVE A
PATIENT IDENTIFIED WITH INCIDENT
USERS OF SEMAGLUTIDE AND IN
APRIL OF 2021 AND REMAINS
OBSERVABLE AND ENROLLED IN
DATASET IN DECEMBER OF 2024
UNDER THE INTENT TO TREAT
ANALYSIS FRAMEWORK, WE WOULD
TING TO FOLLOW THIS PATIENT FOR
OUTCOMES OF INTEREST IN OUR
STUDY POTENTIALLY WELL AFTER THE
DRUG WAS DISCONTINUED.
I WOULD LIKE TO THINK OF THIS
TYPE OF ANALYSIS AS BEING A
LITTLE BIT MORE OF A REALISTIC
SNAPSHOT OF THE WORLD AS IT IS
BAKING ALL OF THE POSSIBLE
OUTCOMES INTO THE CAKE FOR A
PERFECT CONSIDERING INITIATING A
NEW TREATMENT AND PROS OF THIS
APPROACH INCLUDE BY CONTINUING
TO FOLLOW SOMEONE FOR MONTHS OR
YEARS AFTER THEY TAKE A
MEDICATION WE MIGHT BE ABLE TO
BETTER DETECT DELAYED SAFETY
SIGNALS RELATING TO EARLIER
EXPOSURE INCLUDING THINGS LIKE
BIRTH DEFECTS AND ADVERSE
PREGNANCY OUTCOMES BEING DELAYED
SOME MONTHS FOLLOWING DRUG
DISCONTINUED -- STROKE OR
MYOCARDIAL INFARCTION.
ANOTHER UPSIDE TO ITT ANALYSIS,
IT IS SORT OF FROM A POPULATION
HEALTH STANDPOINT IT PROVIDES A
MORE REALISTIC PRAGMATIC VIEW OF
THE BENEFITS AND RISKS OF
STREEMENT INITIATION AND
PREDESCRIBING DRUGS IN CURRENT
CLIMATE OF SHORT ACCESS AND
COVERING SEMAGLUTIDE AND I DON'T
WANT TO ONLY KNOW WHAT HAPPENS
TO PATIENTS THAT REMAIN ADHERENT
FOR THE NEXT TWO YEARS AND WANT
TO UNDERSTAND FULL RANGE OF
POSSIBLE OUTCOMES FOR PERSON
INCLUDING WHAT HAPPENS IF THEY
CAN'T TOLERATE THE MEDICATION OR
STOP TAKING IT AND DOWNSIDES OF
THE APPROACH INCLUDE THAT WE
MIGHT INCORRECTLY ATTRIBUTE A
DISTAL OUTCOME TO TAKING
MEDICINE WHEN IN FACT IT IS
RELATED TO INTERCURRENT EXPOSURE
COMING TO PERSON TAKING GLP-1
AND THIS ANALYSIS WILL BE
IMPACTED BY PREMATURE
DISCONTINUATIONS AND TREATMENT
SWITCHING THAT ARE COMMON NOW
WITH GLP-1 AND WILL DILUTE THE
EFFECTIVENESS MEASURE OF
MEDICATIONS AND MAKE ABILITY
POTENTIALLY TO DETECT SAFETY
SIGNALS IN A SENSE THAT IS ALSO
A LITTLE BIT DILUTED.
ONE OTHER ALTERNATIVE ANALYTIC
APPROACH WITH A DIFFERENT FOLLOW
UP COULD BE ON TREATMENT
ANALYSIS AND SHOWN HERE IS HOW
WE MIGHT APPLY THIS IDEA IN AN
OBSERVATIONAL STUDY WHERE IF A
PATIENT STOPS THEIR ASSIGNED
TREATMENT BEFORE THE END OF THE
STUDY THEY ARE NOT FOLLOWED FOR
OUTCOMES OF INTEREST EVEN IF
THEY ARE STILL TECHNICALLY
OBSERVABLE OR ENROLLED OR AT
RISK AND IN THIS OPTION
CONSIDERING PATIENT BEFORE
STOPPED FOLLOWING PERSON OR
ANALYZING DATA AFTER FOLLOWING
DISPENSING OF SEMAGLUTIDE
TRUNCATING TIME SHE CONTRIBUTES
TO THE STUDY A LOT AND ITT
ANALYSIS MIGHT GIVE A SNAPSHOT
OF THE WORLD AS IT IS WE CAN
THINK OF ON TREATMENT ANALYSIS
AS THE WORLD AS WE WOULD LIKE IT
TO BE AND GETS CLOSER TO THAT
IDEAL CLINICAL TRIAL SCENARIO
WHAT HAPPENS IF 100% PATIENTS
STAY ON MEDICATION AND PROS OF
THIS APPROACH IT WILL GIVE MORE
ACCESS ASSESSMENT OF DIRECT
EFFECT OF BEING ON MEDICATION
AND LOOKING AT REAL-TIME
CONSEQUENCE WE WANT TO LOOK AT
THAT WHILE SOMEONE IS TAKING
MEDICINE NOT 6 MONTHS AFTER THEY
STOP IT AND AFTER THIS APPROACH
WILL PRODUCE EFFECTIVENESS
ESTIMATES THAT CLOSELY ALIGN
WITH CLINICAL TRIALS AND
ADHERENCE RATES WITH R HIGH DUE
TO ONGOING SUPPORT AND DOWNSIDES
OF APPROACH ARE CENSORING
PATIENTS WHEN THEY STOP TAKING
MEDICINE MIGHT CAUSE YOU TO MISS
DELAYED QUALITIES OF EXPOSURE
AND GIVEN CURRENT DIFFICULTIES
THAT PATIENTS HAVE WITH
CONSISTENTLY STAYING ON
MEDICATIONS LONG TERM IN REAL
WORLD COHORTS SUBSET OF FOLKS
YOU WILL HAVE WITH CONTINUOUS
USE OF GLP-1S WILL BE SMALL AND
NOT GENERALIZABLE AND ULTIMATELY
WILL BE RESEARCH QUESTION
WHERE'S ITT ANALYSIS IS
APPROPRIATE AND OTHERS WHERE
ONTREATMENT OR [INDISCERNIBLE]
ANALYSIS MAKES SENSE AND OFTEN
BOTH TYPES OF ANALYSIS CAN BE
USED TO LOOK AT SAME QUESTION
FROM DIFFERENT PERSPECTIVES AND
WILL BE COVERED MORE IN
SUBSEQUENT TALKS AND I WILL END
WITH MENTIONING A COUPLE AREAS
WHERE I THINK CURRENT REAL WORLD
DATA FALLS SHORT WHEN COMING TO
STUDYING GLP-1 MEDICATIONS AND
MENTIONED YESTERDAY AND I WON'T
SPEND A TON OF TIME HERE AS YOU
ARE LIKELY AWARE OF A NUMBER OF
COMPANIES AND HEALTHCARE
PROVIDERS TURNED TO COMPOUNDING
PHARMACIES TO PROVIDE ANOTHER
SOURCE OF GLP-1 MEDS FOR
PATIENTS AND WILL BE I HAVE HARD
TO CAPTURE IN TRADITIONAL REAL
WORLD DATA SOURCES FROM CLAIM
STANDPOINT THESE ARE CASH PAY
AND WE WOULD BE COMPLETELY
UNAWARE OF THEM AND WITHIN A
HEALTHCARE SYSTEM MOST OF THE
TIME THEY ARE NOT NECESSARILY
GETTING THESE COMPOUNDED
MEDICATIONS FROM A DOCTOR WITHIN
THEIR HEALTH CARE SYSTEM GOING
OUT TO A TELEHEALTH COMPANY OR
OUT SOMEWHERE ELSE AND MIGHT
MISS IT THERE AS WELL AND
SOMETHING TO THINK ABOUT IN
TERMS OF A BLINDSPOT AND ANOTHER
RELATIVE BLINDSPOT IS
INFORMATION OF LIFESTYLE CHANGES
HABITS EXERCISE AND BEHAVIORS
THAT PATIENTS MIGHT ENGAGE IN
DURING TREATMENT FOR OBESITY AND
DIABETES AND GET CONCERN FROM
REVIEWERS OF PAPERS TO WHAT
EXTENT ARE BEHAVIORS UNMEASURED
CONFOUNDERS WHEN COMPARING GLP-1
TO PATIENTS USING EXAMPLE OF
OBESITY AND WHAT WE THINK IS
HAPPENING HERE IS IF A PATIENT
TAKING A MEDICATION LEADS THEM
TO BE ABLE TO CHANGE THE WAY
THEY EAT AND LEADS THEM TO BE
ABLE TO BE MORE COMFORTABLE
BEING PHYSICALLY ACTIVE
LIFESTYLE CHANGES ARE ON CAUSAL
PATHWAY TAKING MEDICATION AND
INTEREST AND THUS NOT
CONFOUNDERS AND SIMILARLY IF
FOLLOWING CLINICAL GUIDELINES
AND MANY EDUCATIONS ARE BEING
PRESCRIBED ALONGSIDE LIFESTYLE
BEHAVIORAL ADVICE AND CHANGES
START WITH AOM PRESCRIPTION AND
BOTH GROUPS COMPARING LIKELY TO
GET LIFESTYLE BEHAVIORAL THERAPY
LIFESTYLE CHANGES SHOULDN'T BE
UNMEASURED CONFOUNDERS AND IN
THEORY IF ONE GROUP YOU ARE
COMPARING IS MORE LIKELY TO HAVE
A CERTAIN SET OF LIFESTYLE
BEHAVIORS BEFORE INITIATING
TREATMENT COMPARED TO CONTROL
GROUP AND LIFESTYLE BEHAVIORS
ARE WHAT IS CAUSING OUTCOME OF
INTEREST THIS IS WHERE THINGS
CAN GET PROBLEMATIC AND TO THE
EXTENT POSSIBLE WE WANT TO TRY
TO MATCH OR ADJUST FOR BASELINE
CHARACTERISTICS HIGHLY
REFLECTIVE OF PRE-EXISTING
LIFESTYLE FACTORS.
BIG TAKE-HOME POINTS FOCUSING
ON INCIDENT USERS PEOPLE WILL
GIVE YOU A GOOD IDEA OF SAFETY
AND EFFECTIVENESS OF MEDS IN THE
REAL WORLD AND WATCHING OUT WHEN
BUILDING STUDIES FOR CONFOUNDING
BY INDICATION AND BY
CONTRAINDICATION AND CHOOSING
ACTIVELY TREATED CONTROL GROUP
TO PREVENT RISK OF TIME BIAS AND
CONSIDERING TYPES OF ANALYSIS
DEPENDING ON QUESTIONS YOU ARE
LOOKING AT AND QUICKLY RESEARCH
GAPS AND OPPORTUNITIES I SEE
OBVIOUSLY RIGHT NOW AS FUN AS IT
WOULD BE TO USE REAL-WORLD DATA
TO STUDY LONG-TERM TREATMENT
WITH MEDICINES WE DON'T HAVE
PATIENTS AND ABLE TO DO LONG
TERM TREATMENT TO USE DATA FOR
THAT. THAT IS SOMETHING THAT WE
SHOULD LOOK FOR GOING FORWARD.
AND THEN KEEPING IN MIND THERE
ARE CERTAIN BIG BLIND SPOTS IN
USING REAL WORLD DATA TO STUDY
LIFESTYLE CHANGE AND COMPOUNDED
DRUGS THIS IS NOT WHERE TO DO IT
AND WE DESPERATELY DESPERATELY
NEED STUDIES TO USE REAL WORLD
DATA TO STUDY HETEROGENEITY OF
OBESITY RESPONSE AND ANSWER
QUESTIONS AROUND STEP AND
MAINTENANCE THERAPY AND
SWITCHING THERAPIES AND THANK
YOU TO DR. HALES AND ALL OF THE
OTHER ORGANIZERS OF THE
CONFERENCE FOR THE INVITATION
AND THANK YOU TO MY RESEARCH
TEAM IN BOSTON AND ELSEWHERE WHO
ARE WORKING HARD ON KWIS USING
CLAIMS DATA.
>> KRISTINA, THANKS SO MUCH. IT
WAS QUITE AN AMAZING
PRESENTATION AND REMINDING THE
GROUP TO PUT QUESTIONS INTO THE
Q & A GROUP OR BOX ON THE RIGHT
OF YOUR SCREEN.
SO I WANT TO START OUT WITH ONE
QUESTION THAT CAME IN EARLIER.
IT WAS RELATED TO DOKES.
WOULD YOU SAY IT IS IMPORTANT TO
BE CONSIDERING DOSE OF GLP-1 IN
CRE STUDIES ESPECIALLY IF
LUMPING TOGETHER ON LABEL AND
OFF LABEL PATIENTS INTO A SINGLE
GROUP TAKING A GIVEN DRUG ATHEN
RELATED TO THAT WHAT CHALLENGE
DO YOU SEE RELATED TO THIS.
>> GREAT, GREAT QUESTION AND
SOMETHING THAT IS ONGOING
DISCUSSIONS IN ANY GROUP ON
THIS. DOSE IS REALLY
INTERESTING. IN CLINICAL TRIALS
WHAT WE SAW WAS, YOU KNOW, AT
LEAST IN THE INITIAL CLINICAL
TRIALS FOR SEMAGLUTIDE AND
[INDISCERNIBLE] RIGID UP
TITRATION OF EVERYBODY IN TRIALS
TO MAXIMUM DOSE AND LOOKING AT
PACKAGE INSERT FOR DRUGS IS WHAT
WE ARE SUPPOSED TO DO AND
LOOKING AT WHAT IS HAPPENING IN
CLINICAL PRACTICE HARDLY ANYBODY
IS DOING THAT AND FOR LOTS OF
REASONS AND CLINICAL PROVIDERS
ARE NOT UPTIGHT TRAITING PEOPLE
AND WHAT THEY ARE DOING IS TIGHT
TRAITING PEOPLE BASED ON
TOLLRABILITY AND EFFECTIVENESS
AND WHAT PATIENTS ARE
COMFORTABLE WITH AND THEY ARE IN
ESSENCE TREATING TO TARGET SORT
OF; RIGHT?
AND I THINK USING CLINICAL
JUDGMENT TO FIND DOSE THAT IS
RIGHT FOR THAT PATIENT AND I
WOULD ARGUE SORT OF THAT IF
SOMEONE IS ON A PARTICULAR DOSE
OF MEDICATION AND STAYING ON
THAT DOSE, IT IS PROBABLY
BECAUSE IT IS WORKING FOR THEM
AND TOLERATED AND SHOULDN'T
WORRY TOO MUCH ABOUT IT.
INTERESTING TO LOOK AT PATTERNS
AND ONE THING WE TALKED ABOUT IS
IT POSSIBLE TO LOOK AT PATTERN
OF UPTITRATION AND DOES IT
PREDICT PEOPLE COMING OFF OR
STAYING ON MEDICATIONS IF
CLINICIANS ARE TRYING TOO HARD
TO FOLLOW WHAT WAS DONE IN
CLINICAL TRIALS AND FORCE PEOPLE
UP BEFORE THEY ARE READY ARE WE
GOING TO SORT OF BACKFIRE AND
GET PEOPLE STOPPING MEDS THEY
SAY I CAN'T TOLERATE THIS?
SO I THINK IT IS INTERESTING
DATA TO POTENTIALLY LOOK AT AND
DON'T THINK IT NECESSARILY MEANS
SOMEONE IS NOT BEING TREATED
CORRECTLY IF ON A LOWER DOSE OR
USING IT IN OFF-LABEL WAY.
>> WE REALLY CUT DOWN YOUR
SAMPLE IF YOU DEMANDED IT.
THERE IS A FOLLOW-UP QUESTION ON
TOPIC OF PATIENTS GOING ON AND
OFF MEDICATIONS.
>> YEAH.
>> IF USING A PROTOCOL APPROACH.
CAN YOU REINTRODUCE PATIENTS IF
THEY STOPPED IT AND RESTARTED IT
AND HOW WOULD YOU DEAL WITH IT
ANALYTICALLY?
>> YEAH. THERE IS A COUPLE
DIFFERENT WAYS TO DO THIS AND
ONE WAY THAT OUR GROUP TALKED
ABOUT IS YOU KNOW AFTER -- AFTER
SOMEBODY'S LAST FILL OF A
MEDICATION WITHIN A GIVEN
TREATMENT EPISODE THERE IS SOME
AMOUNT OF TIME AFTER THAT WHERE
WE SORT OF SAY OKAY YOUR LAST
FILL OF MEDICINE YOU HAD 30 DAYS
ON HAND AND LET'S SAY YOU TOOK
IT MOST DAYS, SOME DAYS YOU
DIDN'T. WE WILL GIVE YOU SOME
EXTRA BUFFER PERIOD.
PEOPLE GOING ON AND OFF
MEDICINES NOT BECAUSE THEY
WANTED TO BUT FOLKS COULDN'T
FIND IT AT ANY PHARMACIES FOR A
MONTH OR 2 AND WANT TO BUILD IN
A GRACE PERIOD MODIFIED ANALYSIS
YOU ALLOW UP TO 90 DAY GAP OR
SOMETHING AFTER THAT AFTER THE
LAST FILL AS LONG AS SOMEONE
REINITIATES TREATMENT AND CALLS
IT PART OF THE SAME TREATMENT
EPISODE AND RATHER THAN SAYING
YOU MISSED OUT ON FILLING
MEDICINE EXACTLY FOR DATE WE
LOOKED FOR IT SEEMS CENSORED AND
DOESN'T SEEM FAIR GIVEN SUPPLY
CHAIN CONSTRAINTS OF
ENVIRONMENT.
>> GREAT. THAT IS REALLY
HELPFUL. YOU KNOW, YESTERDAY,
THERE WAS DISCUSSION AROUND
PATIENTS FINDING INTENTION TO
TREAT ANALYSIS TO NOT BE VERY
HELPFUL AND SAY I WANT TO KNOW
WHAT HAPPENS IF I TAKE THIS
MEDICATION AND WE SAW THIS
APPROACH OFTEN PREFERRED AND
DEVELOPMENT OF EVIDENCE SIN THES
HE'S AND WHAT DO YOU THINK DO
ITT ANALYSIS MAKE SENSE IN
CURRENT AREA A LOT OF PEOPLE
WITH OBESITY STAY ON MEDICINES
FOR A FEW MONTHS RATHER THAN
TAKING THEM FOR THE LONG TERM AS
THE LABEL WOULD SUGGEST?
>> I THINK IT IS. IT IS REALLY
IMPORTANT TO CONSIDER THAT. I
-- I STILL THINK THERE IS A
PLACE FOR BOTH. I DON'T THINK
WE SHOULD JUST FOCUS ON ITT AND
DON'T THINK WE SHOULD JUST FOCUS
ON ON TREATMENT.
I -- I THINK IT IS HARDER TO
MAKE A CASE, YOU KNOW, IF DOING
AN ITT ANALYSIS AND YOU WANT TO
LOOK AT 5-YEAR RISK OF
CARDIOVASCULAR OUTCOMES AND
TREATED GROUP ON AVERAGE IS
TAKING MEDICINE FOR ONLY THREE
MONTHS IT DOESN'T REALLY MEAN
ANYTHING AND IS PROBABLY NOT IN
THAT CASE IT IS NOT SO MUCH A
PROBLEM OF ITT AND PRO PROTOCOL
ANALYSIS IS NOT HELPFUL THERE
AND THERE IS A MISMATCH BETWEEN
QUESTION YOU ARE TRYING TO
ANSWER AND ABILITY OF DATASET
RIGHT NOW TO ANSWER THAT
QUESTION. I THINK IF YOU ARE
INTERESTED IN YOU KNOW LET'S SAY
PREGNANCY OUTCOMES OR SOMETHING
LIKE THAT IT MAKES SENSE FOR
ANALYSIS AND PROVIDERS MAKING
DECISION FOR PATIENT PANELS AND
POPULATIONS WANT THOSE ITT
ANALYSIS.
>> HOW ABOUT CAN YOU COMMENT ON
DEALING WITH PRESCRIPTION DATA
VERSUS FILL DATA?
HOW DO YOU MANAGE DATA WILL
IMITATIONS?
>> YEAH. THIS IS A REALLY --
MASHI ELUDED TO THIS YESTERDAY
IN HIS TALK. THE GRASS IS
ALWAYS GREENER AND WHENEVER I
WORK WITH CLAIMS DATA I THINK,
MAN. I WISH I HAD ELECTRONIC
HEALTH RECORD DATA WITH ACTUAL
BMI MEASURES AND BLOOD PRESSURES
AND STUFF AND ONE NICE THING
ABOUT INSURANCE CLAIMS PROVIDED
YOU HAVE PEOPLE WITH PHARMACY
BENEFIT COVERAGE IN YOUR DATASET
IS WE ARE ABLE TO ACTUALLY SEE
WHAT PEOPLE IF ILL AT THE
PHARMACY.
AND WITH ALL MEDICATIONS BUT
ESPECIALLY WITH THESE
MEDICATIONS WHERE THERE IS
STICKER SHOCK AND LOTS OF
NONCOVERAGE OF MEDICATIONS,
THERE IS PROBLEM OF PRIMARY
ADHERENCE IS ENORMOUS; RIGHT?
LOTS OF TIMES DOCTORS WRITE
PRESCRIPTION AND PATIENTS
EXCITED LEAVING OFFICE AND SHOW
UP AT CVS WHO SAYS THAT WILL BE
$1,000 FOR A MONTH SUPPLY AND NO
THANK YOU AND ELECTRONIC HEALTH
RECORD DATA AND LINKED PHARMACY
DATASET YOU ONLY KNOW WHERE
THING WAS PRESCRIBED AND DON'T
KNOW WHAT HAPPENED AND IS AN
IMPORTANT LIMITATION TO KEEP IN
MIND AND RESEARCH EVERIES WILL
DO SOMETHING WHERE THEY REQUIRE
AT LEAST ONE REFILL UP TO BE
ORDERED IN E HR DATA FOR SOMEONE
TO QUALIFY. I THINK YOU START
TO GET INTO A SITUATION THERE
WHERE YOU ARE CONDITIONING
COHORT ENTRY ON A FUTURE EVENT
AND MAYBE PROBLEMS THERE AND
MAYBE YOU START FOLLOW UP AT THE
POINT OF THE FIRST REFILL AND
THEN AGAIN YOU WILL MISS ALL OF
THE PEOPLE WHO MAYBE COULDN'T
TOLERATE EVEN THAT FIRST MONTH
AND EARLY ADVERSE EVENTS YOU
MISSED THERE AND TRADEOFFS AND I
DON'T KNOW. DOES IT ANSWER THE
QUESTION?
>> I THINK IT DOES. ALSO, I
MEAN, PARTICULARLY FOR A LOT OF
TIMES PEOPLE HAVE ONLY USED EHR
AND THINKING OF WORKING WITH
CLAIMS OR ONLY USE CLAIMS AND
THINKING OF WORKING WITH EHR AND
IS HELPFUL TO THINK OF WHAT
TRADEOFFS ACTUALLY ARE AND SORT
OF SIMILARLY WHAT WOULD BE
IMPLICATIONS FOR CLAIMS VERSUS E
HAD. R DATA THINKING OF
GROUPING PATIENTS BASED ON
INDICATION AND IF YOU WANT TO
KNOW WHETHER THEY TAKE IT FOR
OBESITY OR DIABETES OR FOR
WHATEVER REASON.
>> I THINK IT IS PROBABLY WAY
EASIER TO DO THAT WITH
ELECTRONIC HEALTH RECORD DATA
ESPECIALLY IF YOU CAN ACCESS
SOME OF THE UNSTRUCTURED DATA
THAT DR. MENTIONED YESTERDAY AND
CLINICIAN PROGRESS NOTES WHERE
THEY ARE REALLY TALKING ABOUT
THINKING AND DECISION MAKING
PROCESS.
IT WOULD BE ENORMOUSLY HELPFUL
AND OBVIOUSLY IN BIG DATA
SETTING YOU NEED TO USE NATURAL
LANGUAGE PROCESSING OR SOMETHING
TO DO THAT AND KNOW THOSE TYPES
OF TECHNOLOGIES ARE CONSTANTLY
EVOLVING AND PROBABLY WILL
CONTINUE TO GET BETTER BY THE
END OF THE DAY. SO THAT IS
GREAT. I THINK, YOU KNOW, BEING
ABLE TO IDENTIFY WHAT SOMEONE'S,
YOU KNOW, ACTUAL BMI IS AROUND
THE TIME WHEN THEY ARE STARTING
THE MEDICATION IS REALLY HELPFUL
AND TRAJECTORY OF BMI IS LEADING
UP TO STARTING MEDICATION CAN
YOU DO THAT WITH ELECTRONIC
HEALTH RECORD DATA AND CLAIMS
DATA WE MIGHT BE LUCKY AND HAVE
OBESITY DIAGNOSIS THAT IS MORE
COMMON WHEN DOING BARIATRIC
SURGERY RESEARCH INSURANCE
COMPANIES REQUIRE CERTAIN VERY
SPECIFIC BMI CODE TO BE ABLE TO
QUALIFY FOR BARIATRIC SURGERY
AND SEE WELL-POPULATED AND
PROBABLY FAIRLY ACCURATE BMI
CODES AROUND TIME OF BARIATRIC
SURGERY AND THERE IS MISSING BMI
DATA WITH OBESITY MEDICINES AND
OLDER MEDICINES CHEAP OUT OF
POCKET $5 FENTER MEAN I WON'T
TRY TO NECESSARILY FIGHT
INSURANCE COMPANIES ON THAT ONE.
I MIGHT NOT PUT IN SPECIFIC BMI
DIAGNOSIS.
>> MAKES SENSE.
THERE IS A FOLLOW UP THAT IS
GOING BACK TO A POINT FROM A
COUPLE TURNS BACK IN THE
CONVERSATION AND PEDIATRIC
OBESITY MEDICINE DOCTOR WHO GOT
A LOT OF PUSH FROM INSURANCE
PLANS TO FOLLOW EXACT PROTOCOL
AND WONDER HAS THERE BEEN
PUBLISHING AND WE HEARD A COUPLE
TIMES HOW THAT IS NO THE WHAT IS
BEING DONE IN FACT AND IS THERE
PUBLISHED DATA THIS PERSON COULD
PERHAPS LEAN ON A LITTLE BIT AND
LEAD CONVERSATIONS WITH
INSURERS?
>> I FEEL FOR YOU AND SPEND A
LOT OF TIME DEALING WITH PRIOR
AUTHORIZATIONS AND DEALING WITH
PEOPLE GETTING THEIR COVERAGE
REVOKED AND I AM NOT AWARE OF
ANYTHING THAT WOULD SPEAK TO
THAT AND THINK IF IT IS AN
IDENTIFIED NEED FOR RESEARCH
MAYBE THAT IS SOMETHING THAT OUR
CONFERENCE ORGANIZERS COULD JOT
DOWN AS A GAP OR OPPORTUNITY AND
OTHER THING I HEARD IS INSURANCE
COMPANIES REVOKING COVERAGE FOR
PATIENTS WHO ARE NON-COMPLIANT
AND BECAUSE DOCTORS ARE GETTING
SMART AND FIGURING OUT THEY CAN
WRITE, YOU KNOW, A 30-DAY SUPPLY
-- IT LOOKS INSURANCE STANDPOINT
LIKE THIS PERSON HASN'T FILLED
MEDICINE IN THREE MONTHS.
>> NOT LONG TERM.
>> WE WILL CUT THEM OFF AND
AGAIN SOMEONE PUT THIS COMMENT
YESTERDAY AND THOUGHT WAS RIGHT
AND ALL THIS COMES BACK TO HIGH
COST OF MEDICATIONS.
IF WE COULD ADDRESS THAT, I
THINK LOTS OF THESE -- LOTS OF
THESE MESSINESS THAT WE ARE
SEEING IN THE REAL-WORLD DATA
WOULD START TO GET -- GO AWAY.
>> I NOTICE A REALLY INTERESTING
POINT THERE IS A LOT OF
PURPOSEFUL OB FUSS INDICATION OF
DATA BECAUSE OF INCREDIBLY HIGH
COSTS.
>> YEAH.
>> WE HAVE ANOTHER QUESTION
HERE. COULD YOU SHARE
PERSPECTIVE ON TRIAL EMULATION
APPROACH AND POTENTIAL TO OVERIN
HERRIENT CHALLENGES IN
OBSERVATIONAL DATA?
DO YOU SEE THIS TO BE A LIMITING
FACTOR?
>> I THINK -- I MEAN, YOU KNOW,
I THINK WE HAD THE WORLD'S
EXPERT IN THIS TALK ABOUT IT
YESTERDAY.
I DON'T, YOU KNOW, HAVE TOO MUCH
TO ADD ON TOP OF WHAT HE SAID.
I THINK IT IS A REALLY HELPFUL
WAY TO THINK ABOUT THIS. IT IS
JUST NICE TO KIND OF ORGANIZE
AND STRUCTURE YOUR THINKING.
AND -- AND, YOU KNOW, THE
DOWNSIDE IS YOU MIGHT SORT OF
GET THROUGH THAT APPROACH AND
REALIZE THAT I WOULDN'T DO THIS
TRIAL. I SHOULDN'T DO THIS
STUDY. YOU KNOW?
BUT -- BUT IN SOME WAYS THAT IS
A HELPFUL EXERCISE; RIGHT?
TO GET TO THAT.
I DO THINK IT IS HELPFUL. I
THINK, YOU KNOW, AND I -- AND I
KNOW THAT DR. HERNANDEZ
MENTIONED THIS. ONE THING THAT
IS NICE ABOUT IT IS THAT THERE
ARE CERTAIN CLINICAL TRIALS THAT
WE WOULD ALL LOVE TO SEE DONE
BUT ARE NEVER GOING TO BE
FUNDED; RIGHT?
THEY ARE NOT IN ANYBODY'S
FINANCIAL INTEREST IN THE
PRIVATE SECTOR AND ARE TOO LARGE
AND UNWIELDY PROBABLY FOR NIH.
THAT IS WHERE I THINK IT IS
INCREDIBLY HELPFUL AND THINK IT
IS HELPFUL FOR ANSWERING
QUESTIONS THAT FRANKLY WOULD BE
UNETHICAL TO ANSWER WITH A
CLINICAL TRIAL AROUND HARM AND
THAT ARE REALLY IMPORTANT TO GET
RIGHT FROM A, YOU KNOW, DESIGN
STANDPOINT AND INTERNAL VALIDITY
STANDPOINT AND THINK THERE IS A
PLACE FOR BOTH AND I'M A BIG
PROPONENT OF DOING MORE
PRAGMATIC TRIALS AS DISCUSSED
YESTERDAY TO GET ANSWERS FASTER
IN MULTIPLE WAYS.
>> GREAT. WE HAVE ANOTHER
QUESTION HERE ABOUT DO YOU THINK
-- DO YOU HAVE ANY INSIGHTS
ABOUT HOW REAL WORLD DATA COULD
BE USED TO INCREASE
UNDERSTANDING ABOUT
HETEROGENEITY WITHIN GROUP OF
PEOPLE BROADLY LEFT TOGETHER AS
BEING OBESE?
>> YEAH. THIS IS ONE OF -- I
THINK POTENTIAL REALLY UNTAPPED
STRENGTHS OF REAL-WORLD DATA AND
TURNED TO FIELD IN FIRST PLACE
AS CLINICIAN I WOULD GET DARN
FRUSTRATED WHEN I OPEN MEDICINE
AND JAMMA AND TRIAL CAME OUT
LOOKING AT TABLE 1 AND THESE ARE
NOT MY PATIENTS AND TRIALS ARE
RECRUITING PATIENTS THAT ARE NOT
GENERALIZABLE.
I THINK THAT IS WHERE REAL-WORLD
DATA IS SO WONDERFUL IS THAT YOU
KNOW THE PATIENTS ARE INCREDIBLY
HETEROGENOUS IN BASELINE
CHARACTERISTICS AND HOW THEY
RESPOND TO TREATMENT AND SO
THINK USING THAT AND TRYING TO
WORK WITH METHODOLOGISTS OR
TAKING PAIRING A CLINICIAN WHO
UNDERSTANDS WHAT IT LOOKS LIKE
AND WHAT PHENOTYPE LOOKS LIKE ON
THE GROUND AND WORKING WITH
PHARMACOEPIPERSON OR SOME OTHER
TYPE OF METHODOLOGIST WHO CAN
HELP YOU CREATE A DESIGN FOR
YOUR STUDY THAT IS GOING TO
LEVERAGE THAT RATHER THAN, YOU
KNOW, SOMETIMES I THINK THE
TARGET TRIAL PIECE ONE, ONE
MAYBE DOWNFALL IS IF IT LOOKS
LIKE A NARROW CLINICAL TRIAL YOU
END UP EXCLUDING A LOT OF PEOPLE
THAT DON'T AND STUDY DESIGNS WE
MIGHT CONSIDER TO MAYBE THERE IS
A PRAGMATIC TARGET CLINICAL
TRIAL OR SOMETHING THAT WOULD
ALLOW A LITTLE MORE FLEXIBILITY
THERE.
>> TAKE ADVANTAGE OF
GENERALIZABLE POPULATION.
>> EXACTLY.
>> AND MORE RIGOROUS APPROACHES
AND IT IS A GREAT POINT.
SOMEBODY ASKED IF YOU COULD
SPEAK TO FORMING A REGISTRY AND
NOT SURE WHAT ASPECTS OF
REGISTRY THEY ARE CONSIDERING
AND PUT THAT IN IF YOU WANT TO
ADD DETAILS IT MIGHT BE HELPFUL
AND YESTERDAY WE TALKED ABOUT
HOW REGISTRIES COULD BE USEFUL
AND SOMETIMES ARE NOT REAL-WORLD
DATA BUT CERTAINLY IS A LIKENESS
AND WHAT ARE THOUGHTS FOR
REGISTRIES AND RESEARCH RELATED
TO GLP-1S?
>> THEY ARE WONDERFUL TO HAVE
AND POTENTIALLY A REALLY NICE
IDEA WITH ALL THESE TELEMEDICINE
COMPANIES THAT ARE COMING OUT
AND -- AND WHERE, YOU KNOW, ALL
OF THESE PATIENTS ARE NOW BEING
TREATED IN A SPACE WHERE WE
DON'T HAVE EYES ON THEM. RIGHT?
THAT DATA IS NOT SHOWING UP IN
ELECTRONIC HEALTH RECORD AND
INSURANCE CLAIMS AND IS ONE
PLACE IN PARTICULAR WHERE
EITHER, YOU KNOW, I DON'T KNOW
IF WILL IS A POLICY GUIDELINE OR
SOMETHING THAT WOULD REQUIRE IT
OR IF SOMEBODY WANTS TO TAKE IT
ON AND CREATE A REGISTRY OF
PATIENTS THAT ARE TREATED AND
SYSTEMATIC WAY OF COLLECTING
SIMILAR SAFETY AND EFFICACY
MEASURES ACROSS THESE DIFFERENT
COMPANIES WOULD BE REALLY
WONDERFUL AND THINK THAT IS A
DEFINITE NEED AND WITH
BLINDSPOTS IN OUR DATA SETS, YOU
KNOW, DOCTORS AND HEALTH SYSTEMS
WON'T DOCUMENT THINGS THAT ARE
NOT NECESSARILY THAT IMPORTANT
FOR BILLING. THINGS WE MIGHT
REALLY CARE ABOUT AS OBESITY
RESEARCHERS LIKE LIFESTYLE AND
QUALITY OF LIFE AND THOSE THINGS
ARE NOT GENERALLY CAPTURED
SYSTEMATICALLY AND IS ANOTHER
PLACE WHERE LIKE YOU ENVISION A
NICE REGISTRY WHERE PATIENTS ARE
ABLE TO REPORT EXPERIENCES AND
WHAT IS HAPPENING IN THEIR LIVES
AGAIN ON A SYSTEMATIC WAY TO
PAIR IT UP WITH EXISTING
HEALTHCARE AND HEALTH SERVICES
OUTCOMES THAT WE HAVE.
>> YEAH. THAT WOULD BE GREAT.
AND THE IDEAIN CORPORATING
PATIENT REPORTED OUTCOMES THAT
WOULD ADD REALLY GREAT VALUE.
QUESTION. ADDING MORE
INFORMATION ABOUT THEIR THINKING
OF REGISTRY OR PROVIDER INPUTS
DATA FROM PATIENT VISITS.
>> OH, YEAH.
>> TO AVOID THAT CHART AND STEP
THAT IS DOABLE AND TAKES A LOT
OF EXTRA WORK.
>> PUTTING IT IN STRUCTURED DATA
FIELD. YEAH.
>> SO SIMILARLY GOING BACK TO
ONE THING THAT YOU RAISED AS A
-- AS A -- AS A REAL CHALLENGE
WITH A COMPOUNDING MEDICATIONS
THAT, YOU KNOW, WE JUST DON'T
HAVE GOOD DATA IN E HR AND MAYBE
THERE IS DATA IN THE NOTES AND
YOU KNOW NOT NECESSARILY MAYBE
PEOPLE DON'T TELL CLINICIANS
ABOUT IT AND YOU RAISE A POINT
THERE ARE TELEHEALTH COMPANIES
OUT THERE PROVIDING MEDICATIONS.
HAVE YOU SEEN WORK WHERE PEOPLE
HAVE BEEN ABLE TO ACCESS THEIR
DATA AND LINK IT IN WITH EHR
DATA?
>> I IMAGINE THERE ARE PEOPLE
DOING THAT AND KNOW LOTS OF
TELEHEALTH COMPANIES ARE
AFFILIATED WITH, YOU KNOW,
RESEARCHERS AND HAVE PEOPLE
SITTING ON THEIR BOARDS THAT ARE
IN THIS FIELD AND WOULD IMAGINE
THAT IS HAPPENING.
I DON'T KNOW. YOU KNOW, I THINK
SIMILAR TO ANY KIND OF FOR
PROFIT COMPANY, I THINK, YOU
KNOW, YOU JUST HAVE TO VIEW ANY
RESULTING PUBLICATIONS THROUGH
LENS OF LIKE WOULD THEY PUBLISH
THIS IF IT WAS TERRIBLE.
>> YES.
>> PROBABLY NOT. SO I THINK
THERE IS THAT AND IT WOULD BE
REALLY NICE TO HAVIN DEPENDENT
LOOK AT THAT DATA.
>> YEAH. EXCELLENT POINTS.
SOMEONE NOTED THAT THEY ARE
WORKING ON A REGISTRY THAT WAS
JUST SIMILAR TO WHAT WAS JUST
DESCRIBED AND IS GREAT.
>> THANK YOU. THANK YOU FOR
THAT.
>> ALL RIGHT. I THINK WE ARE
RUNNING OUT OF QUESTIONS ON MY
LIST. OH, ONE POPPED UP IN THE
CHAT AND LET ME SEE WHAT THEY
SAY AND DO YOU THINK CURRENT
REAL WORLD DATA ON ADHERENCE ARE
ESSENTIALLY FLAWED AND UNINTERP
RECEIPTABLE AND GIVEN ALL
CHANGES IN HIGH COVERAGE AND
COSTS.
HOW WOULD YOU -- WHAT IS YOUR
ADVICE FOR APPROACHING
ADHERENCE?
>> I WOULD WORK WITH CLINICIANS
PRESCRIBING MEDICATIONS TO HELP
YOU UNDERSTAND PATTERNS YOU ARE
SEEING.
AND I -- I -- IT IS A LITTLE BIT
OF A PET PEEVE. I KIND OF LIKE
-- THE WORD ADHERENCE IN THIS
CONTEXT IS PUTTING THE ONUS ON
THE PATIENT AND SAYING ARE YOU
NOT ADHERENT WHEN THAT IS NOT
WHAT IS GOING ON IN 95% OF THESE
CASES. PEOPLE WANT TO BE ON
MEDS AND STAY ON THEM IF WE CAN
TOLERATE THEM AND HAVE TO COME
UP WITH A BETTER TERM.
>> JUST PLAIN CAN'T GET THEM.
>> YEAH.
>> GREAT. THIS BRINGS US TO END
OF TIMEFRAME AND THANK YOU
AGAIN. IT WAS REALLY A
WONDERFUL PRESENTATION AND GREAT
RESPONSES TO ALL OF THE
QUESTIONS AND.
>> AWESOME. THANK SO YOU MUCH.
>> HAVE A GOOD DAY.
>> OKAY.
>> NOW WE WILL MOVE ON TO A
SERIES OF FOUR TALKS THAT ARE
ALL ADDRESSING REAL WORLD
EFFECTIVENESS AND SAFETY OF
GLP-1-BASED THERAPIES.
AND DR. MCCOY, DR. ROZALINA
MCCOY IS THE FIRST SPEAKER
TODAY. SHE IS AN ASSOCIATE
PROFESSOR OF MEDICINE AND
POPULATION HEALTH AT UNIVERSITY
OF MARYLAND SCHOOL OF MEDICINE
AND RESEARCH LEVERAGES REAL
WORMED DATA -- DIABETES CARE ON
BOTH INDIVIDUAL AND POPULATION
HEALTH BASIS AND IN THIS SESSION
SHE WILL BE ADDRESSING
CARDIOVASCULAR AND METABOLIC
DISEASE AND AS A REMINDER,
PLEASE PUT QUESTIONS IN Q & A.
WE WILL DISCUSS AFTER THIS GROUP
OF PRESENTATIONS.
DR. MCCOY, I WILL TURN THE FLOOR
OVER TO YOU.
>> THANK YOU SO MUCH. AND THANK
YOU TO EVERYBODY WHO IS HERE AND
CONTINUING TO ENGAGE. IT IS
REALLY AN INCREDIBLE WEBINAR AND
HOPEFULLY YOU CAN SEE MY SLIDES.
THEY CHANGED.
>> WE CAN SEE THEM.
>> PERFECT. I HAVE NO
DISCLOSURES AND WHAT I REFERENCE
TODAY IS SUPPORTED BY NI DID.
DK AND PCORI AND YALE AND
UNIVERSITY OF MARYLAND.
WHAT I HOPE TO COVER IN THE NEXT
20 MINUTES ARE THREE THINGS,
FIRST, TALK ABOUT WHAT CARDIO
KIDNEY METABOLIC OUTCOMES AND
NEEDING REAL WORLD DATA AND
CLINICAL TRIALS AND REALLY FOCUS
MOST TIME ON CHALLENGES AND
STRENGTH OF USING REAL WORLD
DATA TO EXAMINE THESE OUTCOMES.
SWITCHING THESE.
>> SYSTEMIC DISORDER THAT IS
CHARACTERIZED BY
PATHOPHYSIOLOGICAL INTERACTIONS
AMONG MULTIPLE METABOLIC RISK
FACTORS DEFINED FUNDAMENTALLY BY
EFFECTS OF FUNCTIONAL ADIPOSITY
IN CARDIOVASCULAR SYSTEM AND
HIGH RATE OF ADVERSE OUTCOMES
ACROSS A WIDE RANGE OF SYSTEMS
AND TALKING ABOUT CKM AS A
SYNDROME TOED IS GLP-1-BASED
THERAPIES DISRUPT THIS PATHWAY
AND RESULTING AND PROFOUND
IMPROVEMENTS IN CARDIOVASCULAR
AND KIDNEY METABOLIC OUTCOMES
FOUND DISCRETELY BEFORE AND
LEADING TO RANGE OF RELATED
ENDPOINTS YOU WILL HEAR ABOUT
DURING THE REST OF THE SESSION
TODAY.
WHAT IS IMPORTANT IS REALLY NEAR
LY.
CONSEQUENCE OF THE SINCOM AND
GREATEST IMPACT OF CKM SYNDROME
IS THROUGH DISPROPORTION BURDEN
OF CARDIOVASCULAR DISEASE AND
OTHER CONDITIONS OCCUR INCLUDING
KIDNEY FAILURE OBSTRUCTIVE SLEEP
APNEA AND SLEEP DECLINE AND
CANCER AND EACH OF THESE
CONDITIONS INDIVIDUALLY IS OVER
A 10 YEAR LOSS IN LIFE
EXPECTANCY AND WHILE WE DON'T
KNOW ALL TOGETHER HOW MUCH
MULTI-MORBIDITY BURDEN OF CKM
IMPACTS LIFE EXPECTANCY WE
EXPECT IT TO BE PROFOUND. IT IS
EXPENSIVE AND THIS IS DATA FOR
2016 ALMOST 481 BILLION DOLLARS
IN DIRECT HEALTH CARE COSTS IN
ADDITIONAL 1.24 TRILLION DOLLARS
IN INDIRECT COSTS WERE
ATTRIBUTED TO THE WIDE RANGE OF
DISEASES DRIVEN BY OBESITY AND
OVERWEIGHT.
THAT IS 9.3% OF THE ENTIRE
USGDP.
WHY DO WE NEED REAL WORLD DATA
GIP GLP-1RASE ARE STANDARD OF
CARE AND CARDIOVASCULAR DISEASE
AND OBESITY AND MULTIPLE DISEASE
ESTABLISHED GLYCEMIC AND
CARDIOVASCULAR AND OTHER
BENEFITS OF THE THERAPIES AND
ONGOING TRIALS THAT CONTINUE TO
FOCUS ON GLYCEMIC AND A1C AND
TIME AND RANGE AND WEIGHT AND
METABOLIC AND CARDIOVASCULAR
OUTCOMES AND WONDERING WHY I'M
HERE AND NOT START WITH THE NEXT
TALK TALKING ABOUT MARGIN TO
NOVEL OUTCOMES AND ARGUING WE
LEARNED YESTERDAY AND EXCELLENT
TALKS ON PRAGMATIC AND
INTERVENTIONAL AND EMULATED
CLINICAL TRIALS REAL WORLD DATA
ALLOW FOR THERAPIES ON CKE
OUTCOMES AND INDIVIDUALS WHO ARE
ACTUALLY TAKING THESE
MEDICATIONS NOT THOSE WHO ARE
STUDIED IN CLINICAL TRIALS WHO
ARE A DISTINCT AND DIFFERENT
PATIENT POPULATION.
AS WELL AS UNDER USUAL CARE
CONDITIONS RATHER THAN
AIDEALIZED CONDITIONS OF
CLINICAL TRIALS AND SPECIFICALLY
THIS ALLOWS US TO STUDY EFFECTS
OF THESE IN PATIENT COHORTS
PAVING WAY FOR US TO UNDERSTAND
HIT ROW GENIUS EFFECTS WE CAN
STUDY INDIVIDUALS TAKING DRUGS
WHO DON'T HAVE CARDIOVASCULAR
CKM DISEASE AND INDICATORS OF
HIGH RISK AND STUDY WOMEN OF
CHILD BEARING POTENTIAL AND
PREGNANCY EXCLUDED FROM ALL
TRIALS AND SIMILARLY CAN LOOK AT
YOUTH AND PATIENTS WITH FRAILTY
AND MULTI-MORBIDITY AND AT RISK
FOR ADVERSE EFFECTS OF THERAPIES
AND ARE BEING TREATED AND SHOULD
BE TREATED WITH MEDICATIONS IN
THE REAL WORLD DUE TO THEIR
BENEFITS AND INDIVIDUALS WITH
TYPE 1 DIABETES WHO EXPERIENCE
HIGH RATE OF CKM AND SYNDROME
COMORBIDITIES AND OFTEN HAVE
BEEN EXCLUDED FROM TRIALS AND
SIMILARLY IT IS IMPORTANT TO
STUDY REAL WORLD CONDITIONS.
BOTH WITHOUT UNDERLYING
LIFESTYLE OPTIMIZATION. AND IN
PATIENTS FACING ADVERSE EVENTS
INTOLLRABILITY COVERAGE BARRIERS
AND DRUG SHORTAGES ADDING TO
PREVIOUS COMMENT ABOUT
IMPORTANCE OF INTENTION TO TREAT
ANALYSIS AND TO ME BIGGEST
BENEFIT OF ITT ANALYSIS IS BEING
ABLE TO TELL MY PATIENT WHAT IS
LIKELY TO BE IMPACT OF THEM
STARTING THIS MEDICATION IF THEY
TAKE IT THE SAME WAY THAT
REALISTICALLY THEY LIKELY WILL
BASED ON DATA FACING
SIDE-EFFECTS AND COST CONSTRAINT
AND FACING DRUG SHORTAGES NOT
IDEAL WORLD WITH NO
INTOLLRABILITY AND DRUG IS FREE
AND ALWAYS THERE WITH NO DELAY
AND I DON'T HAVE TO SPEND HOURS
EVERY WEEK WRITING IT OFF I
THINK UNDERSTANDING WHAT IS
LIKELY TO HAPPEN BASED ON REAL
WORLD EXPERIENCE CAN BE VERY
INFORMATIVE.
SO SOME OF -- I WILL GO THROUGH
THIS QUICKLY FOCUSING ON CKM AND
DR. LEWIS FOCUSED ON THIS A LOT
ALREADY AND HOW DO WE ASSESS CKM
OUTCOMES IN REAL WORLD DATA AND
FOCUSING ON ELECTRONIC HEALTH
RECORDS AND CLAIMS AND
REGISTRIES AND OFTEN THEY ARE
MIX OF THE TWO TO SOME SXENLT
LOOKING AT LABORATORY RESULTS,
THOSE ARE LABS AND BIOMETRICS
AND HEALTH CARE UTILIZATION
EVENTS SUCH AS APPOINTMENTS AND
EMERGENCY DEPARTMENT VISITS AND
HOSPITALIZATIONS AND THOSE ARE
GENERALLY AVAILABLE IN
ELECTRONIC HEALTH RECORD IF
PERFORMED IN INCLUDED HEALTH
SYSTEM AND DEPENDING ON HEALTH
SYSTEM WHOSE EHR YOU WANT TO USE
THAT MAY BE A BIG DEAL OR NOT
DEPENDING ON HOW LEAKY THE
HEALTH CARE SYSTEM IS. FOR
EXAMPLE I'M IN UNIVERSITY OF
MARYLAND AND IN BALTIMORE
LOCATION PATIENTS HAVE OPTION OF
HEALTH SYSTEMS AND PRIVATE
PRACTICES TO GO TO FOR THEIR
CARE. THERE IS A LOT OF LEAKAGE
AND WE MIGHT NOT BE ABLE TO
CAPTURE SUBSTANTIAL NUMBER OF
THEM.
OPPOSED TO NOT UNTIL TWO YEARS
AGO I WAS AT MAYO CLINIC IN
ROCHESTER MINNESOTA MAYO CLINIC
WAS IT AND EXISTING FOR PATIENTS
IN THE CATCHMENT AREA OPPOSED TO
THOSE THAT CAME FOR DESTINATION
CARE. YOU HAVE TO ALWAYS THINK
ABOUT WHAT IS YOUR POPULATION
THAT YOU ARE TARGETING AND WHAT
DOES YOUR EHR LOOK LIKE?
CLAIMS DATA CAPTURED ALL
REIMBURSABLE UTILIZATION.
YOU WILL HAVE KIND OF ALL HEALTH
CARE UTILIZATION EVENTS AS LONG
AS THEY ARE BILLED FOR BUT WON'T
HAVE LAB RESULTS OR BIOMETRICS
UNLESS YOU ARE ABLE TO WORK IN A
SETTING WHERE YOU CAN LINK
CLAIMS AND EHR.
VERBAL METRIC MEASUREMENTS
GENERALLY LIKE WASTE TO HIP
CIRCUMFERENCE, ET CETERA, THOSE
ARE RARELY AVAILABLE IF DONE IN
PRACTICE AND THEY MAY BE
DOCUMENTED IN ELECTRONIC HEALTH
RECORD AS UNSTRUCTURED DATA AND
USING NLPS OFTEN THAT ARE
IMFEASIBLE AND IMPRACTICAL TO
MANY RESEARCHERS AND DEFINITELY
NOT AVAILABLE IN CLAIMS AND
PATIENT REPORTED MEASURES ABOUT
SIDE EFFECTS AND TOLLRABILITY
AND RARELY AVAILABLE AS
STRUCTURED DATA NOT AVAILABLE IN
HR AND CLAIM AND WHEN YOU THINK
ABOUT EACH OF THESE AND NOT ONLY
DO WE THINK ABOUT WHAT IS
FEASIBLE TO BE AVAILABLE BUT
THINKING ABOUT CONSIDERATIONS
AROUND WHAT TYPES OF ENCOUNTERS
ARE COUNTED TO VISITS AND
HOSPITALIZATIONS AND OUTPATIENT
VISITS AND WHAT EXTENT DOES IT
REPRESENT ACTIVE VERSUS
HISTORICAL PROBLEMS AND DO WE
LOOK AT ALL CLAIMS NO THE JUST
THOSE FOR EVALUATION AND
MANAGEMENT INCLUDING LABS;
RIGHT?
IMAGING LINKED DIAGNOSIS AND
WHAT ARE IMPLICATIONS OF EACH OF
THE DECISIONS AND WHAT CODES AND
CODE POSITIONS ARE ACCEPTED TO
ESTABLISH WHETHER OUTCOME OR
COMORBIDITY AND HOW MUCH CODING
VARIATION IS THERE BETWEEN
CLINICIAN AND PRACTICES? AND DO
WE NEED TO REQUIRE CONFIRMATION
OF THAT TO KNOW THAT IT HAPPENED
OR IS THAT A SINGLE EXTENSIVE
DIAGNOSIS THAT IS ENOUGH AND ALL
THESE ARE IMPORTANT
CONSIDERATIONS WHEN WE THINK
ABOUT CAPTURE IING CAPTURING CK
AND BREAKING IT DOWN
SPECIFICALLY WHAT IS THIS THAT
WE MIGHT WANT TO MEASURE?
OUTCOMES THAT ARE MEASURED IN
CLINICAL TRIALS OF
CARDIOVASCULAR OUTCOMES LOOKING
AT HARD OUTCOMES OF MAJOR
CARDIOVASCULAR EVENTS THAT
INCLUDES STROKE VARIABILITY
BETWEEN ISCHEMIC AND MEM ORAGIC
AND THOSE CONSIDERED AND
CARDIOVASCULAR MORTALITY AND CV
OUTCOMES THAT I VIEW AS BEING
IMPACTED BY PATIENTS
SELF-MANAGEMENT AND CARE ACCESS
LIKE ANJIENA TIA AND HEART
FAILURE HOSPITALIZATIONS THAT
ARE HARD OUTCOMES BUT IMPACT --
THERE IS SOME VARIABILITY INTO
COMPLETENESS TO BE ABLE TO BE
SEEN IN REAL WORLD DATA.
AND THERE IS OUTCOMES THAT ARE
IMPACTED BY LOCAL PRACTICES SUCH
AS LOEKING AT REVASCULARIZATION
PROCEDURES AND TRIALS INCLUDE
MECHANISTIC OUTCOMES SUCH AS
FUNCTIONAL STUDIES AND MYOCARD
YUM THAT IS TRULY MORE
RESEARCH-BASED RATHER THAN
PRACTICE AND HOW DO THEY
TRANSLATE INTO THE ABILITY TO BE
IMPLEMENTED IN REAL-WORLD DATA?
AGAIN, BREAKING THINGS DOWN BY
EHR AND CLAIMS.
SO THINGS LIKE ACUTE MI AND
STROKE, THOSE DO GENERATE A
UTILIZATION OF THAT.
WE CAN CAPTURE THAT PREVIOUS
CAVEATS ABOUT LEAKINESS OF
HEALTH SYSTEMS ASIDE.
CARDIOVASCULAR DEATH IS MORE
CHALLENGING REQUIRING LINKAGE TO
DEATH DATA AND ALSO TO CAUSES OF
DEATH.
SO NOT ALL ELECTRONIC HEALTH
RECORDS THAT HAVE A LINKAGE TO
DEATH DATA OR CERTIFICATES THAT
IS HIGHLY VARIABLE AND MANY
CLAIMS WILL PARTIALLY CAPTURE
DEATH BUT NOT ALL PARTICULARLY
FOR COMMERCIAL CLAIMS.
AND IN CAUSE OF DEATH DATA THAT
IS GENERALLY NOT AVAILABLE.
THINGS LIKE ANGINA AND TIA AND
VARIABLE AND INCONSISTENCIES
CODED AND DOCUMENTED
PARTICULARLY AND ANOTHER EVENT
THAT LED TO ANGINA TIA AND
DEPENDING ON WHAT DEFINITIONS
YOU REQUIRE OR CODES OR POSITION
ON THE CLAIM WHETHER YOU REQUIRE
PERINEAR DIAGNOSIS OR NOT YOU
MAY OR MAY NOT SEE IT AND
REVASCULARIZATION PROCEDURES ARE
GENERALLY CAPTURED AND
CARDIOVASCULAR FUNCTIONAL
STUDIES ARE OFTEN NOT PART OF
ROUTINE CARE AND IF ARE IN
FREETAX OF ECHO REPORT FOR
EXAMPLE OR NOT AND AVAILABLE ON
A LARGE SCALE.
SO HERE IS AN EXAMPLE USING REAL
WORLD DATA TO STUDY
CARDIOVASCULAR OUTCOMES AND HERE
WE USE LABS THAT IS A DATA BASE
ADVANTAGE BENEFICIARIES, SORRY
LINKED TO MEDICARE
FEE-FOR-SERVICE CLAIMS AND
LOOKING AT CARDIOVASCULAR
OUTCOMES SHOWING GLP-1 BASED
COMPARISONS WE LOOKED AT FOR
CLASSES OF DRUGS IN PAIRWISE
COMPARISONS AND LOOKED AT MAJOR
CARDIOVASCULAR EVENTS DEFINED AS
MR STROKE AND MORTALITY AND
HEART FAILURE HOSPITALIZATIONS
AND REVASCULARIZATION EVENTS.
WE WR ABLE TO SHOW THAT AS GLT2S
AND GLP-1S ARE COMPARABLE TO
EACH OTHER WITH EXCEPTION OF
HEART FAILURE HOSPITALIZATIONS
AND THEY ARE SUPERIOR TO GLP-1S
NO SURPRISE THEY ARE GLP-1S THAT
GENERALLY ARE SUPERIOR TO DGGP
-- AND PROFOUND INFERIOR TO
GLP-1S AS WELL AS ULTIMATELY ALL
OTHER CLASSES AS WELL.
AND WE CAN MAP IT OUT HERE.
REASON I SHOW THIS IS TO
UNDERSCORE POWER OF REAL WORLD
DATA LOOKING AT NUMBER OF
PATIENTS AT RISK FOR THESE
EVENTS AND THIS WAS IRN VERSE
PROBABILITY OF TREATMENT RATED
COHORT AND YOU CAN SEE THESE ARE
INDIVIDUALS WITH MODERATE RISK
OF CARDIOVASCULAR DISEASE AND
PEOPLE THAT HAVE NOT BEEN PART
OF CARDIOVASCULAR OUTCOMES
TRIALS AND HAD OVER 200,000
INDIVIDUALS WITH URIAS AND
46,000 WITH SGLT2S AND 41,000
WITH GLP-1S AND 82,000 WITH
GLP4S AND THIS THERAPY AND DROP
OFF ALSO OUT OF HEALTH COVERAGE
YOU CAN SEE WE HAVE A LARGE
NUMBER OF PEOPLE CONTINUING TO
HAVE ENROLLMENT AND REALLY
THROUGH 84 MONTHS OF OBSERVATION
PROVIDING POWER TO ASSESS FOR
HETEROGENOUS EFFECT AND
ANALYSIS, ET CETERA THAT ARE NOT
GENERALLY POSSIBLE IN CLINICAL
TRIALS AND MOVING ON TO K,
CLINICAL TRIALS GENERALLY LOOK
AT MAJOR ADVERSE KIDNEY EVENTS
THAT ARE DEFINED REQUIRING
REPLACEMENT THERAPY AND IS
VARIATION BETWEEN TRIALS AS TO
WHETHER THEY TALK ABOUT DIALYSIS
INITIATION AND ONE-TIME EPISODE
AND CHRONIC DIAGNOSIS AND
DEFINING KIDNEY FAILURE OPPOSED
TO ACUTE KIDNEY INJURY AND
PARALLEL TO MACE LOOKING AT
RENAL DEATH AND TRIALS ALSO LOOK
AT SURROGATE OUTCOMES OF
INCIDENT OF PROGRESSIVE ALBUMIN
URIA AND LONG RATE OF DECLINE IN
GFR.
SO THINKING ABOUT HOW CAN WE
OPERATIONALIZE THESE TYPES OF
OUTCOMES AND REAL WORLD DA DATA
KIDNEY FAILURE WE HAVE TO THINK
OF IMMORTAL TIME BIAS TO
ESTABLISH KIDNEY FAILURE AND
[INDISCERNIBLE] WHEN IT IS FIRST
DOCUMENTED AND HOW YOU KNOW
WHETHER IT IS TRULY KIDNEY
FAILURE OR SINGLE EPISODE
WITHOUT REQUIRING THEY SURVIVE
LONG ENOUGH AFTER FIRST DIALYSIS
ENSURE OUTCOME AND DIFFERENT
APPLICATION OF TIME BIAS AND
OUTCOME AND EXPOSURE BUT IS
SIMILAR DEAL AND KIDNEY DEPTH
AGAIN REQUIRES LINKAGE TO
MORTALITY DATA AS WELL AS CAUSE
OF DEATH.
ALBUMINURIA, I FLIPPED MY COST
ANALYSIS, SORRY IT IS AVAILABLE
IN E HR AND NOT IN CLAIMS AND IS
CONTINGENT TO BEING MEASURED.
INCIDENT DISEASE, AS MEASURED BY
GFR WOULD BE AVAILABLE IN E HR
AND NOT -- AND OFTEN NOT IN
CLAIMS UNLESS, YOU KNOW, WE ARE
GOOD ABOUT RELYING ON A
DIAGNOSIS CODES AND WHEN
PATIENTS DEVELOP STAGE 3 OR
HIGHER CKD WE SEE DIEINGOSIS
KOEZED THAT ARE GENERALLY NOT
DOCUMENTED AT ALL AND DECLINE IN
GFR.
YES. CONTINGENT ON THINGS BEING
MEASURED IN CLINICAL PRACTICE
AND SORRY ABOUT THIS MISTAKE AND
HOW DID WE MEASURE IT? SIMILAR
ANALYSIS OF PATIENTS MODERATE
RISK FOR CARDIOVASCULAR DISEASE
NOT HAVING EVIDENCE OF STAGE 3
OR HIGHER DISEASE AS BASELINE AS
DOCUMENTED USING DIAGNOSIS CODES
AND WE COMPARIN KRIDIENTS STAGE
3 OR HIGHER CKD AND DEFINED BY
DIAGNOSIS CODES AND KIDNEY
FAILURE THAT WE DEFINED AS FIRST
DIALYSIS OR KIDNEY TRANSPLANT.
OR, YEAH. PROGRESSION TO KIDNEY
REPLACEMENT THERAPIES USING
DIAGNOSIS CODES AND KIDNEY
REPLACEMENT THERAPY TO DEFINE
THIS AND ANOTHER OUTCOME WE
LOOKED AT ALL CAUSE MORTALITY
AND CAUSE OF DEATH IS NOT
AVAILABLE.
AND IN THIS STUDY, WE FOUND
THAT, AGAIN, GLP-1S ARE SUPERIOR
TO DPP4S AND TO CELL PHONOURIAS
AND SLP2S ARE SUPERIOR TO GLP-1S
FOR KIND OF OUTCOMES THAT EXCEPT
FOR THE INDIVIDUAL WHERE WE
REALLY HAVE A WIDE CONFERENCE
INTERVAL BECAUSE OF LOW NUMBER
OF EVENTS AND AGAIN RELYING ON
CLAIMS DATA ONLY WITHOUT LINKAGE
TO EHR LIMITS ABILITY TO EXAMINE
MANY, YOU KNOW, EARLIER STAGE
OUTCOMES THAT ARE IMPORTANT FOR
STUDYING KIDNEY DISEASE
PROGRESSION.
>> CAN YOU GO BACK -- YOU HAVE
TWO MINUTES LEFT.
>> I'M GETTING THERE.
FINALLY, FOR M, WHAT DO WE
MEASURE?
WE HAVE GLYCEMIC OUTCOMES AND
WEIGHT OUTCOMES AS WELL AS
[INDISCERNIBLE] OUTCOMES WITH
KIND OF EMERGING AS ESSENTIAL
COMPLICATION OF DIABETES
MANAGEMENT AND RISK FACTOR FOR
CARDIOVASCULAR DISEASE.
THESE ARE MUCH HARDER TO FIND
AND ELECTRONIC HEALTH RECORD
WILL GENERALLY MAKE AVAILABLE
A1C AND FASTING GLUCOSE AND
WEIGHT AS WELL AS DIAGNOSIS OF
LIVER FAILURE AND CIRRHOSIS AND
WHAT IS HARDER TO FIND IS CGM
MEASURES THAT ARE OFTEN THOSE
ARE NOT AVAILABLE AS ANALYZABLE
DATA IN E HR BECAUSE THEY ARE
KEPT IN EITHER AS A SCANNED IN
PDF OR UPLOADED PDF OR LIVE IN
REVIEW OR CLARITY PORTALS AND
BODY MEASUREMENTS AND
COMPOSITIONS ARE GENERALLY NOT
AVAILABLE.
CLAIMS, THEY REALLY CAN ONLY BE
USED FOR DIAGNOSIS AND HEART
OUTCOMES AND AVAILABLE FOR LIVER
FAILURE AND CIRRHOSIS AND A SHOW
WE DID TRY TO IN LABS IS LINKED
TO AMBLATTORY LAB RESULTS DATA
AND WE ARE -- OUR TEAM WANTED TO
EMULATE THE GRADE TRIAL
PRAGMATIC COMPARED TO
EFFECTIVENESS TRIAL LOOKING AT
A1C-BASED OUTCOMES EMULATING IT
PRIOR TO GRADES PUBLICATION AS A
FEASIBILITY PROJECT TO SEE IF IT
IS POSSIBLE AND HERE WE COMPARED
GRADES RESULTS TO WHAT WE DID
AND HIGHLIGHTED GLP1-BASED
COMPARI
COMPARISONS.
YOU CAN SEE WE GOT SAME RESULTS
ON SAME DIRECTION AND SAME LEVEL
OF SIGNIFICANCE AND FOR ONE OF
THE COMPARISONS AND OVERLAPPING
CONFERENCE INTERVALS EMULATION
COMPARED TO GRADE TRIALS AND ONE
YOU HAVE LINKED LAB MEASURES,
THOSE ARE USABLE AS WELL AND
VISUALLY THINGS LOOK THE SAME
AND BRIEFLY TO END YOU KNOW CAN
WE DO THIS?
CAN WE KEEP DOING IT FOR OUR
TRIALS?
I LOOKED THROUGH CLINICAL
TRIALS.GOV TO SEE WHAT ONGOING
PHASE III OR HIGHER
INTERVENTIONAL TRIALS WITH CK
OUTCOMES AND OUT OF 32 ACTIVE
TRIALS GLP-1S AND 5 OR NOT FOR
CKM AND YOU CAN SEE HERE WE CAN
IDENTIFY COHORT AND WE CAN
EMULATE COHORT FOR MOST OF THESE
AND WITH THE EXCEPTION THAT WE
HAVE TO MAKE SURE TO CLASSIFY
TYPE 1 DIABETES CORRECTLY AND
PRIMARY OUTCOMES CAN BE ASSESSED
IN THE HALF AND SECONDARY
OUTCOMES GENERALLY CANNOT BE
ASSESSED WITH MOST SECONDARY
OUTCOMES LOOKING AT REALLY
RESEARCH-TYPE OUTCOMES LIKE BODY
COMPOSITION AND [INDISCERNIBLE]
MEASUREMENTS OR MECHANISTIC
ENDPOINTS AND THERE IS TRULY A
COMPLEMENTARY ROLE FOR ALL OF
THE TRIALS.
SO THE COMPLEXITY OF ASSESSING
CAUSALITY FOR KKE OUTCOMES AND
FROM LOTS OF FACTORS DISCUSSED
PREVIOUSLY AND THERE IS A LOT OF
SELECTION BIAS AS DR. LEWIS
DISCUSSED EARLIER THEY ARE
PREFERENTIALLY COVERED BY THOSE
WITH OR ESTABLISHED
COMPLICATIONS AND THOSE THAT
DESIRE TO LOSE WEIGHT AND THOSE
WITH GREATER ACCESS TO HEALTH
CARE RESOURTSS AND FUNDS AND
IMPORTANTLY PURSUIT OF THERAPY
RESULTS IN OVERDOCUMENTATION OF
APPROVED INDICATIONS.
THERE IS HETEROGENOUS TREATMENT
EFFECTS BY BASELINE RISK THAT IS
DIFFICULT AND RISK IS DIFFICULT
TO ASSESS PARTICULARLY USING
CLAIMS.
THERE IS MEDIATION BY MULTIPLE
INTERRELATED OUTCOMES THAT ARE
TIME BEARING CO-VARIATES
PARTICULARLY WEIGHT LOSS AND
GLIESEMIA.
SO THERE IS ALSO SPECIAL
CIRCUMSTANCES IN POPULATIONS
WHERE I THINK THEY ARE REALLY
IMPORTANT TO ASSESS THAT ARE
CHALLENGING METHODOLOGICALLY AND
LOOKING AT COMBINATION THERAPY
AND DISTILLING EFFECTS OF GLP-1S
AND SGLT2S LOOKING AT COMPOUNDED
DRUGS NOT ONLY BECAUSE WE CAN'T
CAPTURE THEM AND BECAUSE WE
DON'T KNOW WHAT IS IN THE
COMPOUNDED PRODUCT THAT MIGHT
NOT BE A GLP-1.
AND/OR WE DON'T KNOW THE DOSE
AND LOOKING AT COMORBID TYPE 1
AND TYPE 2 DIABETES TOGETHER
KNOWING WITH WHO HAS THAT AND
WHO DOESN'T.
SO I WILL END WITH KIND OF MY
DREAM WORLD OF WHAT I THINK WILL
MAKE IT POSSIBLE FOR US TO STUDY
CK OUTCOMES EFFECTIVELY WHEN IT
COMES TO GLP-1 THERAPIES AND
HAVE STANDARDIZEDONTOLOGY AND
CLAIMS TO HELP US KNOW AND
REALLY COMPARE APPLES TO APPLES
WHEN WE ASSESS STUDIES AND NEED
STANDARD DEFINITIONS FOR
CARDIOVASCULAR DISEASE RISK
ASSESSMENT USING CLAIMS AND EHR
DATA AND AMAZING TO HAVE LINKAGE
TO MORTALITY AND CAUSES OF DEATH
AND GREATER ACCESS TO AND USE OF
UNSTRUCTURED DATA HEARING ABOUT
BOTH YESTERDAY AND TODAY.
AND I'M HOPING WE CAN REALLY
WORK TOWARDS GREATER INVESTMENT
IN ALL PAIR CLAIMS DATABASES AND
HEALTH EXCHANGES TO FOLLOW
PEOPLE NO MATTER WHERE THEY SEEK
CARE AND INVEST IN CLAIMS AND
EHR LINKAGES TOGETHER TO SEE
BOTH SIDES OF THE PUZZLE AND HOW
EVERYTHING FITS TOGETHER.
SO SOME DAY I HOPE THAT THIS
DREAM WORLD WILL ENSURE TOWARDS
REALITY AND TURNING IT TO
COLLEAGUES TO TALK ABOUT OTHER
CKM EXTENDED OUTCOMES AND THEIR
WORK THERE.
>> THANK YOU SO MUCH FOR
TERRIFIC OVERVIEW OF REALLY
IMPORTANT RESEARCH AREA AND
SHIFTING TO DIFFERENT SET OF
OUTCOMES.
ESTE WILL JOIN US CLINICAL
PSYCHOLOGIST AND INVESTIGATOR
WITH KAISER PERMANENTE NORTHERN
CALIFORNIA DIVISION OF RESEARCH
USING QUANTITATIVE AND
QUALITATIVE METHODS TO STUDY
WAYS TO PERSONALIZE AND
INTEGRATE CARE FOR PEOPLE WITH
MENTAL ILLNESS WITH GOALS OF
IMPROVING MENTAL HEALTH OUTCOMES
AND CHRONIC DISEASE PREVENTION
STATUS AND TODAY WILL DISCUSS
REAL-WORLD EFFECTIVENESS AND
SAFETY OF GL1 THERAPIES IN
REGARD TO PSYCHIATRIC CONDITIONS
AND THANKS SO MUCH FOR
PRESENTING TODAY AND I WILL TURN
THE FLOOR OVER TO YOU.
>> WONDERFUL. ONE MOMENT.
GREAT. CAN YOU SEE MY SLIDES?
AM I UNMUTED.
>> YES.
>> VERY GOOD. GREAT. THANKS SO
MUCH FOR THIS CHANCE TO TALK
ABOUT THIS TOPIC AND I REALLY
APPRECIATE SHARING THIS TIME
WITH OTHER WONDERFUL SPEAKERS
AND I'M GRATEFUL TO DR. LEWIS
FOR STANDING UP METHODOLOGICAL
DETAILS IN TALKS FOR POPULATION
AS WELL AND I HAVE NO CONFLICTS
TO REPORT.
IN THIS PREEF PRESENTATION I
WILL TALK ABOUT POTENTIAL
IMPACTS OF GLP1 BASED
MEDICATIONS ON BEHAVIORAL HEALTH
CONDITIONS IN PARTICULAR
INCLUDING MENTAL ILLNESS AND
SUBSTANCE USE DISORDER AND WILL
TALK THROUGH SPECIFIC STUDY
DESIGN ISSUES FOCUSING ON
PARTICULAR POINTS THAT ARE
SPECIAL FOR THIS POPULATION.
I WILL FOCUS ESPECIALLY ON
TARGET TRIAL EMULATION STUDIES
USING ELECTRONIC HEALTH RECORD
DATA AND IN SOME WAYS REAL WORLD
DATA CONTRIBUTE TO UNDERSTANDING
AND ALSO SHOULD BE COMPLEMENTED
AND EXTENDED THROUGH CLINICAL
TRIAL EVIDENCE.
I WILL PULL EXAMPLES FROM A
BUNCH OF DIFFERENT BEHAVIORAL
HEALTH CONDITIONS THAT WILL BE A
JUST KIND OF QUICK SNAPSHOT BUT
I WILL TALK ABOUT SUICIDE,
DEPRESSION, ADDICTION, AND
EATING DISORDERS.
MENTAL HEALTH CONDITIONS ARE
VERY COMMON ADDICTIONS AND THEY
ARE VERY COMMON AND CONDITIONS
THAT CAUSE SUFFERING AND ARE
OFTEN ARE UNDERTREATED IN US IN
GIVEN YEAR 1 IN 12US ADULTS HAS
MAJOR DEPRESSIVE EPISODE AND 1
IN 10 AMERICANS AGE 12 HAS
ALCOHOL USE DISORDER AND WHEN
CONDITIONS ARE SEVERE THEY CAN
BE A CAUSE OF GREAT DISABILITY
AND CAN BE BURDEN SOME TO OUR
SOCIETY AND CAN BE
LIFE-THREATENING AND MOST PEOPLE
ARE NOT TREATED RIGHT AWAY IF AT
ALL.
AND I WANT TO EMPHASIZE THAT
THERE HAVE NOT BEEN ADVANCES IN
MENTAL HEALTH TREATMENT AND
OUTCOMES IN THE SAME WAY YOU
HAVE SEEN IN OTHER AREAS AND
MEDICINE.
FOR EXAMPLE, WE ARE SEEING OVER
THE LAST COUPLE DECADE
INCREASING RATES OF SUICIDE IN
THE US THAT IS ACTUALLY NOT
HAPPENING IN OTHER COUNTRIES AND
SUICIDE IS HIGHLY CORRELATEDED
MENTAL ILLNESS AND SUBSTANCE USE
DISORDER AND ALONG
IDIMPROVEMENTS AND AREAS AND
REDUCTIONS FROM DEATH IN HEART
DISEASE AND CHRONIC ILLNESSES
AND MEDICAL CONDITIONS AND ONE
THING I THINK ABOUT WITH
MEDICATIONS IS POSSIBILITY THEY
ARE NEUROPROTECTIVE AND PERHAPS
COULD BE ANOTHER SET OF TOOLS WE
USE FOR A HIGHLY VULNERABLE
POPULATION AND ANOTHER THING TO
THINK ABOUT IS OTHER KINDS OF
MORTALITY IN THIS POPULATION AND
WE HAVE SEEN LAST COUPLE YEARS
NOW NOTWITHSTANDING OVERALL
INCREASED LIFE EXPECTANCY IN THE
US AND PERSISTENT CHALLENGE IS
MORTALITY GAP FOR PEOPLE WITH
MENTAL ILLNESS AND ADDICTION AND
SEE PEOPLE WITH CONDITIONS DIE A
DECADE OR TWO DECADES EARLIER
WITH PEERS WITHOUT MENTAL
ILLNESS AND LOOK AT GAPS IN OWN
HEALTH SYSTEM THINKING KAISER
PERMANENTE PATIENTS HAVE
INSURANCE AND ACCESS TO MEDICAL
CARE AND FOUND SUBSTANTIAL GAP
SO PATIENTS WITH SERIOUS MENTAL
ILLNESS OR SUBSTANCE USE
DISORDER DIED EARLIER THAN WOULD
BE EXPECTED BASED ON YEAR OF
THEIR BIRTH AND TENDED TO DIE
NOT OF SUICIDE OR INJURIES OR
HOMICIDE BUT TENDED TO DIE OF
QUOTE UNQUOTE NATURAL CAUSES
THAT ARE DRIVEN BY METABOLIC
CONDITIONS SUCH AS OBESITY AND
DIABETES AND PATIENTS HAVE A
HIGHER RATE OF DEATH FROM THESE
CHRONIC CONDITIONS.
SO SOMETHING TO CONSIDER WITH
GLP-1 BASED MEDICATIONS IN TERMS
OF IMPACT IS PERHAPS THEY CAN BE
USED TO TREAT METABOLIC
CONDITIONS THAT ARE MORE COMMON
IN THIS POPULATION AND IF THEY
ALSO HAVE SOME KIND OF
NEUROPROTECTIVE EFFECT THAT IS A
DOUBLE BLESSING FOR THIS
POPULATION THAT IS JUST VERY
VULNERABLE TO MULTIPLE KINDS OF
COMORBIDITIES.
HERE I WILL GIVE A VERY QUICK
OVERVIEW OF PRELIMINARY DATA ON
CONDITIONS AND I HOPE THAT I DO
NOT NEGLECT IMPORTANT POINTS BUT
WILL DO MY BEST IN A LIMITED
TIME AND FIRST WITH SUICIDE
RISK.
SO I HAVE BEEN TALKING SO FAR
ABOUT POTENTIAL BENEFITS OF
THESE MEDICATION.
THERE ARE AS WAS MENTIONED IN A
COUPLE OF TALKS YESTERDAY
POTENTIAL RISKS AS WELL.
ONE HAS EMERGED FROM AEARLY
SURVEILLANCE DATA FOR SOME OF
THE MEDICATIONS INCREASED
SUICIDAL IDEATION OR BEHAVIOR
AND THERE HAS BEEN A LOT OF WORK
IN THE AREA THAT IS ONLY
EMERGING NOW AND I THINK THAT WE
HAVE TO KEEP OUR EYE ON THIS.
IT IS STILL UNCLEAR WHAT ANSWERS
WILL BE.
I REMEMBER HEARING YESTERDAY TOO
THAT FDA IS WORKING ON
REAL-WORLD STUDY TO TRY TO
UNDERSTAND THIS BETTER AND SOME
RECENT ANALYSIS OF OBSERVATIONAL
DATA AND CLINICAL TRIAL DATA
HAVE SUGGESTED THAT MAYBE THERE
IS NOT INCREASED RISK OR MAYBE
EVEN MEDICATIONS ARE PROTECTIVE
AGAINST SUICIDAL BEHAVIOR AND
ARE LOTS OF LIMITATIONS IN THE
WORK AND OBSERVATIONAL DATA THAT
HAS METHODOLOGICAL LIMITATIONS
MENTIONED EARLIER RELATED TO NOT
HAVING ACTIVE COMPARATOR AND
CLINICAL TRIALS COME FROM
STUDIES OF MEDICATIONS IN
RELATION TO WEIGHT LOSS OR
DIABETES AND STUDIES INCLUDE
POPULATIONS THAT DON'T HAVE
MENTAL HEALTH HISTORY OR LOW
RISK FOR SUICIDE TO BEGIN WITH
AND SOMETHING TO KEEP AN EYE ON.
WITH REGARDS TO ADDICTION, THERE
HAS BEEN A LOT OF EXCITEMENT
ABOUT USING MEDICATIONS TO TREAT
ALCOHOL USE DISORDER OR
SUBSTANCE USE DISORDERS THAT IS
BASED ON PRE-LYNNE CAL DATA AND
ANECDOTES AND STUFF YOU READ ON
REDDIT THAT PEOPLE DESCRIBE A
REDUCED DESIRE TO USE SUBSTANCES
AND THIS TYPE OF EFFECT IS BEING
BORN OUT IN EMERGING
OBSERVATIONAL AND REAL-WORLD
DATA RIGHT NOW AS WELL AS
CLINICAL TRIAL EVIDENCE THAT
THERE IS SOME NEW WORK THAT HAS
BEEN DONE IN ALCOHOL USE
DISORDER AND SOME WORK IS
UNDERWAY IN OPIOID USE DISORDER
AND SUBSTANCE USE DISORDERS ARE
ALSO BEING STUDIED AND WITH
REGARD TO EATING DISORDER THIS
IS A NUANCED PICTURE. WE KNOW
FROM ANECDOTAL DATA THAT SOME
PATIENTS USE GLP-1 BASED
MEDICATIONS IN A WAY THAT
WOULDN'T BE RECOMMENDED AND THEY
ARE RESTRICTING CALORIE INTAKE
AND THIS IS PART OF MORE AN
EATING DISORDER PRESENTATION.
BUT ON THE FLIPSIDE, IT IS
POSSIBLE THAT THESE MEDICATIONS
COULD BE HELPFUL FOR BINGE
EATING THAT IS A BEHAVIOR THAT
IS SEEN FOR SUBSTANTIAL MINORITY
OF PEOPLE THAT HAVE EXCESS
WEIGHT.
SOME EARLY SMALLER TRIALS AND
OBSERVATIONAL DATA SUGGESTED
THAT MEDICATIONS CAN HELP
CERTAINLY WITH WEIGHT LOSS AND
REDUCTION IN EATING AND ALSO MAY
BE HELPFUL FOR SOME OF THE
COGNITIONS AND SPECIFIC BEHAV
BEHAVIORS THAT YOU SEE WITH
BINGE EATING DISORDER AND WE
HAVE TO BE CAUTION HERE BECAUSE
WE HAVE TO FULLY EVALUATE
DIFFERENT OUTCOMES AND
MECHANISMS THAT COULD BE RELATED
HERE AND IS POSSIBLE THAT PEOPLE
ARE YOU KNOW TAKING MEDICATIONS
AND SEEING REDUCED BINGE EATING
AND HAVING MALADAPTIVE BEHAVIORS
AND THOUGHTS THAT ARE A
DIFFERENT KIND OF EATING
DISORDER AND WITH REAL WORLD
DATA THERE IS POTENTIAL TO
INCLUDE A LARGE SAMPLE AS BEEN
SAID EARLIER WITH INCLUSIVE
POPULATION AND TRY TO PICK UP
AND DETECT INITIAL EVIDENCE
RELATED TO RISKS AND BENEFITS
AND DATA CAN BE HELPFUL AND
ALREADY HAVE INFORMED LABELING
DECISIONS WITH, YOU KNOW, WITH
REGARD TO SUICIDE RISK.
HERELY TOUCH ON IDEAS AROUND
MEASUREMENT AND I REALLY
APPRECIATE DR. MCCOY TALKING
THROUGH ISSUES EARLIER AND WILL
TRY TO FOCUS IN ON ISSUES
SPECIFIC TO BEHAVIORAL HEALTH
AND LOOKING AT MENTAL HEALTH
DIAGNOSIS AND REAL-WORLD STUDIES
USE DIAGNOSTIC AND ICD CODES TO
MEASURE NOT JUST THINGS LIKE
DEPRESSION BUT ALSO SELF-HARM
BEHAVIOR CODED IN THE HEALTH
RECORD AND LIMITATION OF MINE OF
COURSE IS THEY ARE STIGMATIZED
CONDITIONS THAT ARE OFTEN
UNDERREPORTED AND MEDICATIONS
YOU KNOW OBVIOUSLY IT IS
IMPORTANT TO MEASURE USE OF
MEDICATIONS AND ACTIVE
COMPARATOR AS WELL AS OTHER
CONCOMITANT TREATMENTS AND
HEALTH CONDITIONS AND IN OUR
SYSTEM WE HAVE A ROBUST SET OF
DATA RELATED TO DISPENSING IN
OUR SYSTEM IT IS CLOSED SYSTEM
AND DELIVERY SIFTIN IT EGG
GREATED WITH PAYER AND INSURANCE
COMPANY NOT ALWAYS AVAILABLE IN
E HR DATA.
WITH OTHER TYPES OF DATA
ELEMENTS SUCH AS BMI OR
LABORATORY RESULTS, THAT CAN BE
AVAILABLE IN ELECTRONIC HEALTH
RECORDS AND SOMETIMES IN
STRUCTURED FIELDS AND THEY CAN
BE HARD TO USE IN STUDIES
BECAUSE MAYBE THEY ARE NOT
ASCERTAINED VERY REGULARLY
ACROSS THE LARGE POPULATION THEY
ARE INTERESTED IN AND YOU HAVE
TO CONSIDER WHAT DATA GENERATION
MECHANISM IS THAT LED TO
PARTICULAR DATA ELEMENTS.
WE ARE ABLE TO LINK ELECTRONIC
HEALTH RECORD AND CLAIMS DATA TO
OUTSIDE DATA SOURCES THAT IS
IMPORTANT WHEN STUDYING SUICIDE
AND YOU ARE ABLE TO EVALUATE
CAUSE OF DEATH BY DOING THIS
LINKAGE.
IN ELECTRONIC HEALTH RECORDS YOU
ARE SOMETIMES ABLE TO ACCESS
PATIENT-REPORTED OUTCOMES.
MOST USEFUL ONES ARE THOSE PART
OF SCREENING MEASURES THAT ARE
QUESTION AIRS THAT ARE
ADMINISTERED VERY BROADLY TO
LOTS OF PEOPLE TO MEASURE THINGS
LIKE DEPRESSION OR SUICIDAL
IDEATION.
WE ALSO HAVE BRIEF SCREENING
PROTOCOLS THAT ARE JUST VERBAL
WHERE LET'S SAY MEDICAL
ASSISTANT RECORDS IN HEALTH
RECORD WHEN PATIENT COMES IN
WHAT THEIR DRINKING OR SMOKING
HISTORY IS LIKE AND ADDING A
CAVEAT THAT YOU HAVE TO KNOW
MORE ABOUT WHAT IS HAPPENING IN
DELIVERY SYSTEM AND DOING
RESEARCH AND DATA ELEMENTS ARE
NOT STRUCTURED AND NOT EASILY
ACCESSIBLE AND IN TERMS OF
PATIENT-REPORTED OUTCOMES I WILL
HIGHLIGHT WORK THAT IS ONGOING
FOCUSING ON DRINKING AND MEANS
TO STUDY NOW AND COLLEAGUE
VANESSA IS WORKING ON ANALYSIS
USING SCREENING DATA FOR ALCOHOL
USE AND ABLE TO USE FEW ITEMS
THAT ARE REGULARLY USED
CLINICALLY TO CALCULATE AVERAGE
DRINKS PER WEEK THAT IS
EMULATING A TARGET TRIAL TO
UNDERSTAND THE ASSOCIATION
BETWEEN GLP-1 BASED MEDICATIONS
AND CHANGES IN DRINKING OVER THE
COURSE OF A YEAR.
AND IN A SIMILAR STUDY THAT HAS
BEEN PUBLISHED RECENTLY ONLINE
COLLEAGUES AT THE VA HAVE
SIMILARLY USED ALCOHOL SCREENING
DATA AND HAVE REPORTED A GREATER
REDUCTION IN DRINKING BEHAVIOR
FOR PATIENTS WHO ARE RECEIVING
GLP-1 BASED MEDICATIONS.
AND INTERESTINGLY, A STRONGER
EFFECT FOR MORE SEVERE LEVELS OF
DRINKINGCA INDICATED BY ALCOHOL
USE DISORDER DIAGNOSIS AND
BUILDING ON EARLIER REMARKS FROM
SPEAKERS ABOUT HOW TO DEFINE
POPULATIONS AND COMPARATORS I
WILL FOCUS IN ON HOW WE DO THIS
WITH REGARD TO BEHAVIORAL HEALTH
AND SOMETHING THAT IS IMPORTANT
TO CONSIDER IS THAT MEDICATIONS
ARE NOT REALLY PRESCRIBED FOR
BEHAVIORAL HEALTH CONDITIONS AT
THE MOMENT AND MIGHT CHANGE AS
OFF USE LABEL INCREASES WITH
GREATER EVIDENCE AND STUDIES YOU
HAVE TO REMEMBER THAT PATIENTS
INCLUDING FALL INTO OVERLAP
BETWEEN INDICATIONS FOR WHICH
MEDICATIONS BEING PROVIDED AND
SOME KIND OF ELEMENT OF RISK
FOFR BEHAVIORAL HEALTH CONDITION
AND WE CAN EMULATE A STUDY
LOOKING AT COLLATERAL EFFECT
WITHIN OTHER OVERLAP POPULATION
AND SAYING COLLATERAL EFFECT I
REFER TO UNINTENDED OR SECONDARY
OUTCOME OF INTERVENTION THAT IS
FOCUSING ON CHANGES IN BEHAVIORS
AND HEALTH CONDITIONS NOT
PRIMARY TARGET OF INTERVENTION
AND COLLATERAL EFFECTS ARE IDEA
COMING UP MORE IN BEHAVIORAL
RESEARCH AND IN A SENSE COMMON
SIDE-EFFECTS GI AND SYMPTOMS ARE
TYPE OF CHICANO/CHICANA
LATINO/LATINA EFFECT AND MIGHT
BE INTERESTED IN EFFECTS OF
MEDICATIONS AND INTERVENTIONS
NOT ANTICIPATED AND SOME COULD
BE POSITIVED REDUCED DRINKING
BEHAVIOR AND IMPROVED MOVE MOOD
AND SOME NEGATIVE PERHAPS
CHANGES IN MOOD THAT ARE
DEPRESSIVE AND INCREASED
SUICIDALITY OR EATING DISORDER
AND THINKING ABOUT DEVELOPING A
TARGET TRIAL EMULATION STUDY YOU
FOCUS IN ON OVERLAP POPULATION
AND SIMILAR TO WORK DESCRIBED
EARLIER YOU WANT TO JUST FIGURE
OUT WHAT SLICE OF THE POPULATION
WOULD BE ELIGIBLE FOR BOTH GLP-1
BASED MEDICATION AND OTHER
ACTIVE COMPARATOR GROUP FOCUSING
IN ON NEW USERS AND CAN LOOK AT
COLLATERAL EFFECT AS OUTCOME AND
ANOTHER CONSIDERATION THAT I
THINK IS IMPORTANT TO THINK
ABOUT AND VALUABLE FOR FUNDERS
FOCUSING ON RESEARCH IS
IMBEDDING STUDY OF COLLATERAL
EFFECT WITH LARGER PARENT TRIAL
THAT MIGHT BE FOCUSED ON
ENTIRELY DIFFERENT OUTCOME OF
INTEREST AND PERHAPS COLLATERAL
EFFECT THAT MIGHT FIT IN WITH
ORIGINAL STUDY POPULATION THAT
COULD BE ADDITIONAL OUTCOME OF
INTEREST TO STUDY.
A STUDY I WANT TO HIGHLIGHT THAT
DOES THIS IS TARGET DM STUDY --
TRIALS USING TARGETED LEARNING
AND IS BEING CO-LED BY MY
COLLEAGUE AND PAT TRICK O'CONNOR
AT HEALTH PARTNERS INSTITUTE OF
MINNESOTA AND HAVE TAKEN A LARGE
DATA SET FROM 6 DIFFERENT HEALTH
CARE SYSTEMS ACROSS THE COUNTRY
AND THIS DATA SET INCLUDES MORE
THAN 50 MILLION DIABETES DRUG
FILLS THAT ARE DOING A -- YOU
KNOW, REAL WORLD DATA TARGET
TRIAL EMULATION HEAD TO HEAD
COMPARISON AMONG DIFFERENT
DIABETES MEDICATIONS AND PRIMARY
OUTCOME OF INTEREST IS MAJOR
ADVERSE CARDIOVASCULAR EVENTS
AND ALONG WITH THIS AND STUDY IS
SUPPORTED AND FUNDED BY PCORI
AND IT IS INTERESTED IN.
>> PARTICIPANT: PARTNER
ENGAGEMENT AND RESEARCH THAT IS
PARTICULARLY MEANINGFUL TO
PATIENTS IS MOOD AND DEPRESSION
AND OUR COLLABORATOR STEPHANIE
HOOKER HEALTH PARTNERS LEADS
ANALYSIS FOCUSED ON INCIDENT
DEPRESSION MEASURED BY ICD CODES
STUDYING WITHIN HEAD TO HEAD
COMPARISONS POTENTIAL EFFECTS ON
OUTCOME AND MENTIONING COLLEAGUE
JULIE HAS BEEN LEADING PARTNER
ENGAGEMENT WORK THAT IS SO
INFLUENTIAL HERE. STRENGTHS OF
THIS APPROACH THAT I MENTIONED
THE FIRST COUPLE HERE THAT
INCLUDE DISPENSING DATA FROM
PHARMACY AND ALL THESE SYSTEMS
INVOLVED IN THE STUDY HAVE
INTEGRATION BETWEEN DELIVERY
SYSTEM AND PAYER AND ARE ABLE TO
PRESUMABLY MEASURE WHETHER
PATIENTS ARE GETTING MEDICATIONS
AND OF COURSE WITH CAVEATS THAT
GLP-1-BASED MEDICATIONS NOW ARE
BEING OBTAINED NOW THROUGHOUT
THE SYSTEM AND DISCUSSED THAT
AND INNOVATIVE METHODS TEAM IS
USING TO ADJUST FOR BASELINE
CONFOUNDING AND TIME VARYING
FACTORS THAT COULD BE DIFFERENT
BETWEEN DIFFERENT GROUPS IN EACH
COMPARISON AND REMAIN HAS BEEN
ABLE TO USE SOPHISTICATED
TARGETING LEARNING METHODS USING
COMBINATION OF DIFFERENT
APPROACHES INCLUDING PROPENSITY
SCORES AND MACHINE LEARNING TO
ADJUST FOR SOME POTENTIAL
CONFOUNDING AND RECENTLY WHEN I
TALKED TO STEPHANIE SHE
MENTIONED THAT MODELS ARE
COMPUTATION ALLEY INTENSIVE
TAKING WEEKS TO RUN AND CAN BE A
DIFFICULT TASK TO DO THIS AND IS
A RIGOROUS WAY OF APPROACHING
VARIOUS COMPARISONS AND APPROACH
IS INTERESTING AND WON'T TELL
BUT THEM THEY ARE NOT PUBLIC
YESTERDAY AND LOOK OUT FOR MORE
ON THE STUDY AND IN YOUR FUTURE
AND WANT TO MENTION OTHER WORK
PUBLISHED IN THE LAST YEAR OR
SO.
SO WE HAVE SEEN MORE REAL WORLD
STUDIES ON SUICIDE DEATH AND
BEHAVIOR AND SUICIDAL IDEATION
AND STUDY FROM UADA USING EXTAND
NAVIAN REGISTRY DATA USING NEW
ACTIVE USER COMPARATOR TYPE OF
APPROACH. THEY FOUND THERE
WASN'T EVIDENCE FOR INCREASED
SUICIDE DEATH RISK THAT IS A
HARD ONE TO STUDY BECAUSE WHEN
YOU ONLY HAVE TWO OR THREE YEARS
OF FOLLOW UP DATA YOU ARE NOT
EXPECTING TO SEE SUICIDE DEATH
IN A SHORT TIME PERIOD AND HAVE
TO CONTINUE TO BE CAUTION ABOUT
THIS AND THEY FOUND A SMALL
PROTECTIVE EFFECT FOR ANOTHER
SUICIDALITY OUTCOMES THAT IS A
COMPOSITE OF FATAL AND NON-FATAL
ATTEMPTS.
ANOTHER EXAMPLE OF REAL WORLD
DATA BEING USED WAS IN THE STUDY
OF OPIOID OVERDOSE AND SO WONG
AND COLLEAGUES USED FEDERATED
HEALTH CARE DATA AND COMPARED
TIED TO A BUNCH OF DIFFERENT
KINDS OF DIABETES MEDICATIONS
AND GLP-1 RECEPTOR AGONISTS AND
FOUND GLUTIDE WAS ASSOCIATED
WITH LOWER RISK OVERDOSE IN 1
YEAR FOLLOW UP PERIOD AND HAD
PRETTY SMALL SAMPLES FOR EEP OF
THE COMPARISONS 1 THOUSAND TO
2,000 PATIENTS AND PROPENSITY
MATCHED TO ADJUST FOR SOME
CONFOUNDING AND NOW EATING
DISORDER TREATMENT IS NOT MY
AREA OF SXEERT TE-- EXPERTISE A
LOOKED AT LITERATURE AND
APPROACHES THERE AND WELCOME
FEEDBACK FROM LISTENERS THAT ARE
EXPERTS IN THIS AND CONDITION
STUDYING REAL WORLD DATA AND YOU
MIGHT FIND THAT PEOPLE LOSE
WEIGHT AND REDUCE RISK OF EATING
BUT HAVE TO UNDERSTAND BETTER
MALADAPTIVE THOUGHTS AND
BEHAVIORS THAT COULD UNDERLINE
AN EATING DISORDER AND COULD BE
SATURDAYS HERBATED DURING COURSE
OF TREATMENT WITH MEDICATIONS
AND PEOPLE THAT ARE DEVELOPING
MORE FOCUS ON WEIGHT OR BODY AND
THIS COULD BECOME A PROBLEMATIC
SITUATION.
AND OF COURSE THERE COULD BE
PATIENTS THAT DON'T HAVE AN
EATING DISORDER AT THE BEGINNING
OF TREATMENT THAT DEVELOP A NEW
EATING DISORDER AS PART OF THEIR
TREATMENT.
WE REALLY DO NEED TO UNDERSTAND
THIS BETTER AND SOMETHING I HAVE
BEEN WONDERING ABOUT IS WHAT --
WHETHER INCIDENT EATING DISORDER
SIMILAR TO EATING INCIDENT
DEPRESSION AND SUICIDE BEHAVIOR
OUTCOME COULD BE SAFETY OUTCOME
IN STUDIES USING REAL WORLD DATA
PERHAPS MEASURING EATING
DISORDER THROUGH CODES AND GIVE
INITIAL SENSE WHETHER THERE IS A
RISK EFFECT THERE.
IN SUMMARY, REAL WORLD DATA CAN
FILET NEED FOR DISCOVERING
POTENTIAL BENEFITS AND RISKS FOR
BEHAVIORAL HEALTH AND DATA
MEANINGFULLY COMPLEMENT RCTS
WHEN YOU HAVE ENOUGH DATA YOU
ARE ABLE TO INCLUDE LOTS OF
DIFFERENT PEOPLE AND RESULTS
COULD BE GENERALIZABLE BECAUSE
OF THAT.
THEY CAN ALSO HELP US TO STUDY
LOW FREQUENCY OUTCOMES AND AS
MENTIONED EARLIER YOU MIGHT NEED
MORE DATA THAN CURRENTLY WHAT WE
HAVE AND SOME OUTCOMES LIKE
SUICIDALITY AND ALSO EATINGIN
KRIDIENTS CAN BE A VERY LOW RATE
AND MULTI-SITE STUDIES ARE
IMPORTANT AND FUTURE WORK SEEMS
IMPORTANT TO MAXIMIZE PATIENT
REPORTED MEASURES NATURE OF
BEHAVIORAL HEALTH CONDITIONS AND
THINGS WE NEED TO LEARN ABOUT
FR
PATIENTS REPORT AND MEASURE THAT
IS ROUTINELY SCREENED WE WON'T
BE ABLE TO CAPTURE IT EASILY AND
STRUCTURE HEALTH RECORD DATA AND
MIGHT BE SOME OTHER MEASURES OR
METHODS WE COULD USE IN THE
FUTURE THAT CAPITALIZE ON
SEMISTRUCTURE UNSTRUCTURED TEXT
FROM NOTES. SO THIS WOULD BE IN
AREA OF NATURAL LANGUAGE
PROCESSING OR LARGE LANGUAGE
MODELING AND HAVEN'T SEEN THIS
STUDY AND COULD BE AREA OF
FUTURE FOCUS AND ANALYSIS I
MENTIONED EARLIER ABOUT TARGETED
LEARNING IS AN IMPORTANT METHOD
TO CONTINUE TO DEVELOP TO TRY TO
CREATE RIGOROUS COMPARISONS
BETWEEN DIFFERENT CONDITIONS AND
SOMETHING I DIDN'T GET TO TALK
ABOUT THAT IS IMPORTANT IS
HETEROGENEITY AND ONE TYPE OF
HETEROGENEITY THAT HAS BEEN
NEGLECTED HAS BEEN PREVIOUS
MENTAL HEALTH HISTORY AND SO IT
IS A BIT EASIER SO FAR WITH REAL
WORLD DATA TO STUDY INCIDENT
TYPES OF BEHAVIORAL HEALTH
OUTCOMES CREATING CLEANER TYPE
OF COMPARISON AND CAN YOU HAVE A
SORT OF WASH OUT PERIOD THAT CAN
YOU TRY TO FOCUS ON PEOPLE WHO
DON'T HAVE PREVIOUS MENTAL
HEALTH CONDITIONS AND CLINICALLY
WOULD BE USEFUL TO KNOW HOW WE
ADVISE PATIENTS COMING IN WITH
PRE-EXISTING SUICIDALITY AND
MOOD DISORDER AND THESE PATIENTS
I FOCUS ON A LOT IN RESEARCH WHO
HAVE SERIOUS MENTAL ILLNESS AND
HOW THESE MEDICATIONS ARE
EFFECTING THEM.
THIS IS SOMETHING THAT WE NEED
TO TACKLE AND NEED TO HAPPEN IN
RANDOMIZED CONTROL TRIALS AND IN
TERMS OF WHY TRIALS CONTINUE TO
BE IMPORTANT. I MEAN, SAME
ISSUES COMING UP IN OTHER TALKS
APPLY HERE AND I WANT TO
EMPHASIZE THAT YES REAL WORLD
DATA DOES OR IS INCLUSIVE WHEN
YOU CONSIDER RCTS ARE DONE TO
STUDY GLP-1 BASED MEDICATIONS
FOR WEIGHT LOSS OR DIABETES AND
WILL INCLUDE PEOPLE WITH GREATER
MENTAL HEALTH RISK IN REAL WORLD
DATA AND SOMETHING UNIQUE ABOUT
PEOPLE WITH BEHAVIORAL HEALTH
CONDITIONS WHERE THEY MIGHT NOT
GET INTO REAL WORLD DATA EITHER.
RCTS MIGHT NEED TO BE DESIGNED
NOT JUST FOR WEIGHT LOSS BUT FOR
THIS POPULATION AND REALLY
CONSIDER INCLUSIVE ISSUES THERE.
SO THERE ARE PEOPLE WHO ARE NOT
IN REAL WORLD DATA WHO ARE NOT
BEING OBSERVED BECAUSE THEY HAVE
UNDIAGNOSED DEPRESSION AND DON'T
COME UP IN HEALTH RECORD AS
HAVING DIAGNOSIS AND DON'T GET
INTO THE STUDY AND MIGHT BE ON
THE FRINGES OF ELIGIBILITY FOR
THESE MEDICATIONS.
AND SO MAYBE THEY COULD BENEFIT
FROM IT AND ARE NOT GETTING IT
BECAUSE THEY DON'T HAVE A HIGH
ENOUGH BMI AND DON'T HAVE TYPE 2
DIABETES YET AND COULD BENEFIT
PRANCE AND ANOTHER ISSUE IS
ACCESS CHALLENGES MENTAL ILLNESS
AND SUBSTANCE USE DISORDER AND
ECONOMIC STRUGGLES AND PATIENTS
MIGHT NOT BE ABLE TO GET
MEDICATIONS AT ALL AND IS
GENERALLY LOTS OF STIGMA AND
CHALLENGES NAVIGATING HEALTH
PERSISTENCE FOR THIS POPULATION
AND THEY MIGHT NOT BE ABLE TO
GET MEDICATIONS BUT PERHAPS IF
WE DESIGN A TRIAL WELL ENOUGH WE
CAN REACH PATIENTS AND ASSESS
HOW THEY DO ON MEDICATIONS.
AND THAT IS WHAT I HAVE FOR YOU
AND WANT TO SAY THANK YOU TO MY
COLLEAGUES AT KAISER AND
NORTHERN CALIFORNIA AND
COLLABORATORS AND THANKING
NATIONAL INSTITUTES OF MENTAL
HEALTH FOR SUPPORTING ME AS
EARLY STAGE INVESTIGATOR WITH
DEVELOPMENT AWARD AND FUNDERS OF
RESEARCH AND THANKS TO ALL OF
YOU FOR BEING HERE AND FOR THE
ORGANIZERS OF THE WORKSHOP.
>> NOW WE ARE GOING TO 2I7B TO
RUN AND PHARMACEUTICAL OUTCOMES
AND POLICY PHARMACOINFORMATICS
DISCUSSING REAL WORLD
EFFECTIVENESS AND GL1 THERAPIES
IN REGARDS TO NEURODEGENERATIVE
DISEASES AND WITH TALKS PUT
QUESTIONS IN Q & A PANEL AND
DISCUSS THEM AFTER SET OF FOUR
PRESENTATIONS WHY DON'T YOU GO
AND TAKE THE FLOOR?
>> THANKS FOR NICE INTRODUCTION
AND LET ME SHARE MY SCREEN.
CAN EVERYONE SEE THE SLIDE?
>> YES.
>> THANK YOU FOR HAVING ME FOR
THIS WORKSHOP. IT IS A GREAT
HONOR TO BE HERE TODAY GIVING A
PRESENTATION ON TOPIC OF JOB
RECEPTOR AGONISTS AND
NEURODEGENERATIVE CONDITIONS AND
IN THIS TALK I WILL
[INDISCERNIBLE] DEMENTIA AND
ALSO BRIEFLY TOUCHING ON
EMERGING EVIDENCE RELATED TO
[INDISCERNIBLE] DISEASE AND THIS
IS MY DISCLOSURE AND RESEARCH
THAT IS SUPPORTED BY SEVERAL
FEDERAL AGENCIES AS WELL AS
FORMER FOUNDATION AND PRESENTING
TODAY IS MY OWN. IN THE NEXT 18
MINUTES I WILL START WITH
BACKGROUND ON INTERSECTION OF
OBESITY AND DIABETES AND
[INDISCERNIBLE] RELATED DEMENTIA
AND WILL BRIEFLY REVIEW CLINICAL
TRIAL LANDSCAPE FOR TOPIC THAT
IS SPECIFICALLY ON GLP-1 AND
DEMENTIA OUTCOME AND GOING INTO
REAL-WORLD EVIDENCE IN ADDITION
TO SHARING EXISTING REAL WORLD
STUDIES ON TOPIC AND WILL ALSO
DISCUSS METHODOLOGICAL
CHALLENGES SPECIFIC TO REAL
WORLD STUDIES IN THIS SPACE AND
I'M GLAD TO HEAR PREVIOUS
SPEAKERS COVERED GENERAL ISSUES
IN GLP-1 STUDIES USING REAL
WORLD DATA.
CURRENTLY MORE THAN 7 MILLION
AMERICANS AGE 65 AND OLDER ARE
LIVING WITH ALZHEIMER'S DISEASE
NUMBER PROJECTED TO DOUBLE TO 14
MILLION AND ALREADY CURRENTLY IS
7TH LEADING CAUSE OF DEATH IN
UNITED STATES AND MORTALITY RATE
CONTINUES TO RISE.
IT IS STRIKING TO SEE THAT.
MANY OTHER CHRONIC DISEASE LIKE
STROKE AND HEART DISEASE
MORTALITY IS DECREASING IN PAST
TWO DECADES AND THE ADRD
MORTALITY HAS BEEN RISING A LOT
AND DESPITE GLOWING ECONOMIC
CONDITION EFFECTIVE TREATMENT
OPTION REMAIN OR ARE LIMITED
URGING NEEDS PREVENTIVE
STRATEGIES AND THERAPEUTIC
TARGETS.
SO LET'S TALK ABOUT A LITTLE OF
GLP-1 AND HAVING TO TALK A LOT
ABOUT RECEPTOR AGONISTS
YESTERDAY AND TODAY AND WE KNOW
IT IS AN ISSUE AND
[INDISCERNIBLE] FOR TREATMENT OF
TYPE 2 DIABETES AND EXPANDED TO
MANAGEMENT BECAUSE OF
SIGNIFICANT BENEFIT OF LOWER
BODY WEIGHT AND SO BASED ON A
RESEARCH [INDISCERNIBLE]
PUBLISHED IN [INDISCERNIBLE]
LAST YEAR CURRENTLY BASED ON
EXIST
EXISTING 236789 /* --
POTENTIALLY ELIGIBLE FOR
RECEPTOR AGONISTS AND SOME
GROUPS FOR EXAMPLE HAVE BECOME
BEST SELLING DRUG IN US IN 2023
IN A COUPLE YEARS APPROVED IN
MARKET AND OWN WORK USING DATA
FROM DATA FLORIDA WE OBSERVED A
MORE THAN 10 INCREASE IN JOB
HUMOR RECEPTOR AGONISTS USED
BETWEEN 2020 AND 2023 IN ALL
THESE THREE YEARS REFLECTING
RAPID UPTAKE OF THERAPIES IN
REAL WORLD SETTINGS TYPE 2
DIABETES ALZHEIMER'S DISEASE AND
RETHEY LOWER BODY WEIGHT AND
OBESITY DIABETES POPULATION THEY
HAVE NEUROPROTECTIVE EFFECT AND
PRECLINICAL AND TRANSLATIONAL
STUDIES SUGGEST THAT GLP-1
RECEPTOR AGONISTS DELAY SEVERAL
KEY PATHWAYS INCLUDING REDUCING
-- AND MITIGATING OXIDATIVE
STRESS AND ALL TOGETHER
INTERSECTION FORMS STRONG
BIOLOGICAL RATIONAL FOR
INVESTIGATING GLP-1 AGONIST FOR
POTENTIAL STRATEGY FOR DEMENTIA
TREATMENT.
CURRENTLY NO RANDOMIZED TRIALS
HAVE BEEN PUBLISHED TO
SPECIFICALLY ASSESS THE DEMENTIA
OUTCOMES WITH GLP-1 RECEPTOR
AGONISTS AND EVIDENCE-BASE COMES
FROM MY ANALYSIS OF EXISTING
METABOLIC OUTCOME RCTS.
THIS IS ONE OF OUR INITIAL
METAANALYSIS OF CARDIO METABOLIC
OUTCOME TRIALS AND WE EVALUATED
21 RANDOMIZED TRIALS INCLUDING A
TOTAL OF 167 PARTICIPANTS
OBSERVING THE SIGNAL AND
SUGGESTING A PROTECTIVE
POTENTIAL BENEFIT OF GLP-1
RECEPTORS IN REDUCING RISK OF
MUSCULAR DIM ENSHH AND WHILE
NUMBER OBSERVED IN ADR ONES ARE
VERY, VERY LOW IN THESE TRIALS
AND MOST OF THE ASSOCIATION DID
NOT REACH STATISTICAL
SIGNIFICANCE IN DEMENTIA OUTCOME
AND CONDUCTED UPDATED NETWORK
METAANALYSIS THAT INCLUDE 26RCT
THIS TIME AND INVOLVING ALMOST
200,000 PARTICIPANTS AND IN THIS
NETWORK WE EXAMINED A TOTE AFTER
OF SIX CLINICAL DOMAINS
ASSESSING 21 INDIVIDUAL HEALTH
OUTCOMES AND WE FOCUS ON
NEURODEGENERATIVE DISEASE DOMAIN
AND MOST FINDINGS RELATED TO
DEMENTIA AND PARKINSON'S DISEASE
REMAIN NONSIGNIFICANT AND
FUNDING POINTING OUT DIRECTION
AND UNDERSCORE LIMITATIONS OF
RELYING ON EXISTING METABOLIC
TRIALS RELATING TO DEMENTIA AND
OTHER DEGENERATIVE OUTCOMES AND
CURRENTLY TWO LARGE RCTS ONGOING
IN WORK AND IN EVOKE PLUS
INVOLVING EARLY ALZHEIMER'S
DISEASE PATIENTS AND EACH TRIAL
ENROLLED ABOUT 1,800
PARTICIPANTS APPLYING TO FOLLOW
UP TO THREE YEARS AND MAIN
RESULT WOULD BE EVALUATED AT END
OF THE SECOND YEAR AND EXTENSION
RESULT WILL BE EVALUATED IN THE
END OF 9 THIRD YEAR.
WE ARE REALLY LOOKING FORWARD TO
RESULTS HOPEFULLY COMING OUT IN
NEXT FEW MONTHS IN LATE 2025 AND
2026.
IN SUMMARY SO FAR TREATMENT
CENTER SEVERAL KEY LIMITATIONS
IN THIS CONTEXT THAT IS
PERCEIVED IN EVALUATING ADRD
OUTCOME. FIRST DEMENTIA
OUTCOMES TYPICALLY REQUIRE VERY
LONG-TERM FOLLOW UP THAT IS VERY
DIFFICULT TO ACCOMMODATE IN MOST
OF THE CLINICAL TRIAL SETTINGS.
ALSO SAMPLE SIZE IN THIS TRIAL
[INDISCERNIBLE] TREATMENT ACROSS
SUBGROUP OF PATIENT POPULATION
AND CHALLENGES UNDERSCORE
CRITICAL ROLE OF ROBUST
REAL-WORLD EVIDENCE IN FIELDING
KNOWLEDGE GAP AND PROVIDING
COMPLEMENTARY INSIGHTS INTO LONG
TERM NEUROPROTECTIVE POTENTIAL
FOR JOB QR RECEPTOR AGONISTS
LET'S LOOK INTO REAL-WORLD
EVIDENCE AND CONDUCT ANALYSIS OF
OBSERVATIONAL STUDIES AND FROM
THAT THAT IS ABOUT 2 TO 3 YEARS
AGO.
WE IDENTIFY STUDIES AND INSPECT
THEM AND FROM THAT ALL THREE
[INDISCERNIBLE] DRUGS RECEPTOR
[INDISCERNIBLE] GL2 INHIBITORS,
INHIBITORS ARE SIGNIFICANTLY
ASSOCIATED WITH LOWER RISK OF
[INDISCERNIBLE] DEMENTIA. AS
YOU CAN SEE THAT THE ANALYSIS
REVIEWED SUBSTANTIAL HETERAUTO
JENAETY ACROSS STUDIES AND ALSO
NONE OF THESE INCLUDED STUDIES
ADJUSTED FOR IMPORTANT
CONFOUNDERS SUCH AS BMI IN
HEMOGLOBIN A1C AND LIMITATIONS
POINT TO NEEDS FOR MORE
RIGOROUSLY DESIGNED REAL WORLD
STUDIES THAT ACCOUNT FOR KEY
METABOLIC FACTORS.
SO IN OUR OWN STUDY, WE EMULATED
A TARGETED TRIAL USING REAL
WORLD DATA FROM FLAR DAH AND
ELECTRONIC HEALTH RECORD AND
CONDUCTED THREE EMULATED TRIAL
COHORT AND ONE COMPARING GLP-1
RECEPTOR AGONISTS TO OTHER LINE
GLUCOSE [INDISCERNIBLE] IN OUR
PATIENTS AND SECOND COMPARING
SGLT2 INHIBITORS VERSUS OTHER
GLUCOSE LOWERING DRUG AND THIRD
COHORT CONDUCTING DIRECT HEAD TO
HEAD COMPARISON OF GLT1 -- STUDY
DESIGNED FOLLOWING AN ALREADY
CONVENTIONAL
PHARMACO[INDISCERNIBLE] ACTIVE
NEW USER ACTIVE COMPARATOR
INTEND TO TREAT.
SO OUR FINDINGS SHOWED A
SIGNIFICANT LOWER RISK OF
ALZHEIMER'S DISEASE AND RELATED
DEMENTIAS AND ASSOCIATED WITH
GLP-1 RECEPTOR AGONISTS IN THIS
THE GREEN LINE IS FOR GLP
RECEPTOR AND RED LINE FOR OTHER
SECOND LINE GLUCOSE LOWERING
DRUGS AND RESULTS WERE
CONSISTENT ACROSS SUBGROUPS IN
GENERAL. WE CAN SEE SOME
SUBGROUPS THAT WE HAD SAMPLES
ISSUE OVERALL DIRECTION AND WERE
VERY CONSISTENT ACROSS THESE
SUBGROUPS.
SIMILARLY, SGLT2 INHIBITORS
ASSOCIATED WITH LOWER RISK ADRD
COMPARED TO OTHER GLUCOSE
LOWERING DRUGS AND AGAIN IN A
COUPLE OF NEAR GRAPH THE GREEN
LINES THAT EXTENDS FOR SGLT
INHIBITORS AND GLUCOSE LOWERING
DRUGS AND PRE-SPECIFIED SUBGROUP
ANALYSIS WERE CONSISTENT AND
WHEN DIRECTLY COMPARING JOB
RECEPTOR AGONISTS TO SGL
INHIBITORS THERE IS NO REAL
SIGNIFICANT DIFFERENCE OBSERVED.
WE THEN USED THE CAUSAL AM
METHOD TO EXPLORE HETEROGENEITY
FACTORS THROUGH DATA DRIVEN
APPROACH AND MODELS
INTERESTINGLY REVIEWED SPECIFIC
SUBGROUPS THAT BENEFIT RISK
ACTUALLY WERE THOSE WHO HAD
HIGHER BASED METABOLIC RISK AND
THOSE PEOPLE SEEM TO GET MORE
NEUROPROTECTION BENEFIT FROM
GLP-1 RECEPTOR AGONISTS AND FOR
EXAMPLE FOR BOTH GLP-1 AND SGLT2
INHIBITOR GROUPS, PEOPLE WITH
BOTH CARDIOVASCULAR
[INDISCERNIBLE] AND
CARDIOVASCULAR CONDITIONS
BENEFIT THE MOST FROM LOWER ADRD
RISK FROM RECEPTOR COMPARED TO
OTHER GLUCOSE LOWERING DRUGS AND
PATTERNS FOUND IN SGLT2
INHIBITORS AND EVEN THOUGH IN
THE COMPARISON BETWEEN THESE
INHIBITORS EVEN THE OVERALL
AVERAGE BENEFIT WAS SIMILAR
BETWEEN TWO GROUPS AND PATIENTS
WE OBSERVED THAT PATIENTS WITH
THIS AND THIS MAY BENEFIT MOST
FROM GLP RECEPTOR AGONISTS
COMPARED TO SGLT2 INHIBITORS AND
STEP FORWARD WE APPLIED A CAUSAL
MEDIATION ANALYSIS TO
INVESTIGATE WHETHER THE
IMPROVEMENT IN HEMOGLOBIN A1C
AND BMI TWO WILD KNOWN CARDIO
METABOLIC MARKERS MIGHT EXPLAIN
OBSERVED NEUROPROTECTIVE IN FACT
OF GLP-1 RECEPTOR AGONISTS ON
ADRD RISKS AND IS A -- YEAH. WE
TRY TO QUANTIFY TO WHAT EXTENT
THOSE BIOMARKERS PLAY A ROLE AS
A CAUSAL MEDIATOR.
INTERESTINGLY, OUR RESULTS
SHOWED THAT THE REDUCTION OF
ADRD RISK ASSOCIATED WITH GLP-1
RECEPTOR AGONISTS USED APPEAR TO
BE LARGELY INDEPENDIENT OF THIS
OR BMI AND PROPORTION OF
MEDIATED THROUGH EITHER
HEMOGLOBIN A1C AND
[INDISCERNIBLE] WITHOUT
STATISTICAL SIGNIFICANCE AND
WORKING WITH REAL WORLD DATA AND
SPECIFIC TOPIC COMES WITH OWN
SIDE OF CHALLENGES AND HAVE
THREE OF THEM HERE.
FIRST OF ALL ADRD IS OFTEN
MISCLASSIFIED WHEN USING ONLY
ICD CODES AND APPLYING DATA
COMPUTATIONAL PHENOTYPES IS
CONSIDERITY CALLING AND ALSO AS
WE KNOW THAT NEURODEGENERATIVE
DISORDERS INCLUDING ADRD ONSITE
AND MAY PROCEED BEFORE THE
MEDICATION EXPOSURE BECAUSE OF
THE DELAYED DIAGNOSIS AND
CAREFUL CONSIDERATIONS ON STUDY
DESIGN AND SENSITIVITY ANALYSIS
IS VERY IMPORTANT.
OUR FIRST SPEAKER COVERED A LOT
OF THE CHALLENGES IN SELECTING
COMPARATORS AND THERE IS REALLY
NO APPROPRIATE ACTIVE COMPARATOR
DRUG FOR GLP-1 RECEPTOR AGONIST
IN WHICH [INDISCERNIBLE] SO FAR
AND CHALLENGE FOR US TO HAVE
THOSE CONFOUNDING INDICATION.
THIS IS A CASE STUDY THAT
DESCRIBED DEVELOPMENT
COMPUTATIONAL PHENOTYPE AND THIS
USED FOR EHRE DATA AND THIS
PERFORMING CD ALGORITHM BASED ON
THIS REQUIRED PRESENSE OF TWO AD
RELATED CODE AND AT LEAST ONE
RELEVANT KEY WORD IDENTIFIED IN
CLINICAL NODES AND THIS USING
DATA FROM [INDISCERNIBLE] AND WE
EXTERNALLY VALIDATED INTO
INDEPENDENT HEALTHCARE NETWORKS.
OKAY. BEYOND ALZHEIMER'S
DISEASE AND DEMENTIA THIS IS
ALSO BEING INVESTIGATED FOR
PARKINSON'S DISEASE.
THIS PHASE 2 TRIAL WAS PUBLISHED
LAST YEAR AND SHOWED THAT
[INDISCERNIBLE] THERAPY RESULTS
IN LESS PROGRESSION OF MOTOR
DISABILITY THAN PLACEBO AT 12
MONTHS AND IS VERY EXCITING AND
[INDISCERNIBLE] DATA. HOWEVER,
IN THIS YEAR, A COUPLE OF MONTHS
AGO, PHASE 3 TRIAL WITH
[INDISCERNIBLE] PUBLISHED DID
NOT PUBLISH IN LESS THAN AND DID
NOT CONFORM DISEASE MODIFYING IN
FACT FOR PARKINSON'S DISEASE AND
BOTH CLINICAL TRIALS MORE SAMPLE
SIZE AND COVERED PEOPLE WITH
EARLY PARKINSON'S DISEASE AND
OUR INITIAL TARGET TRIAL
EMULATION STUDY WAS CONDUCTED
ABOUT TWO YEARS AGO.
BACK THEN, WE EXAMINED AMONG
PATIENTS WITH TYPE 2 DIABETES
AND AGONISTS WITH
[INDISCERNIBLE] INHIBITORS IN
RELATION TO PARKINSON'S DISEASE
RISK AND FOUND THAT GLP-1 WAS
ASSOCIATED WITH A LOWER RISK OF
DEVELOPING PARKINSON'S DISEASE
SEEN IN THIS PARAGRAPH BLUE
LINES FOR THIS RECEPTOR AGONIST
AND THESE INHIBITORS.
SO BY FAR, A LOT OF STUDIES ARE
LOOKING AT THE HIGH RISK
POPULATION OLDER AGE AND
DIABETES AND OBESITY METABOLIC
PROFILE IN RISK OF CLINICAL
ENDPOINT SUCH AS [INDISCERNIBLE]
IN THIS ONGOING PROJECT WE
EXAMINE THE EFFECT OF GLP
RECEPTOR AGONIST IN PATIENTS
WITH REM SLEEP BEHAVIOR DISORDER
AND STRONG [INDISCERNIBLE]
INDICATOR OF PARKINSON'S DISEASE
SPECIFICALLY SEEING WHETHER THIS
IMPACT ON DISEASE PROGRESSION.
WE LOOK AT THE IMPACT OF GLP-1
ON PHENOCONVERSION RISK AND
TIMING FROM RBDE TO PARKINSON'S
DISEASE THIS STUDY IS
PRELIMINARY FUNDING AND SAMPLE
PATIENTS WITH [INDISCERNIBLE]
AND THEY ARE PROMISING THIS VERY
LARGE COMPETENCE INTERVAL THAT
IS A SMALL SAMPLE SIZE AND WE
ARE NOW EXPANDING ANALYSIS TO
INCLUDE A BROADER POPULATION
THAT IS [INDISCERNIBLE] TAKE
AWAY MESSAGE USE OF THIS
RECEPTOR AGONIST EXPANDED
SIGNIFICANTLY AND SMALL
ITERATION IN ADRPD AND OTHER
NEURODEGENERATIVE DISORDER RISKS
WITH WIDESPREAD IMPLICATIONS AND
THIS FACE INHERIENT LIMITATIONS
OBSERVING LONG TERM OUTCOMES AND
DIFFICULTIES IN IDENTIFYING
HETEROGENEITY AND TREATMENT
EFFECT AND ROBUST REAL-WORLD
EVIDENCE IS CRITICALLY NEEDED TO
EVALUATE IMPACT OF CHRONIC GLP-1
EXPOSURE ON RISK OF THESE
NEURODEGENERATIVE CONDITIONS.
THAT IS IT. THANK YOU. THANK
YOU VERY MUCH FOR THE ORGANIZER
IN THE AUDIENCE AND OUR PEER
SPEAKER IN THE SESSION. THAT IS
IT.
>> THANK YOU SO MUCH FOR THIS
REALLY WONDERFUL PRESENTATION ON
SUCH IMPORTANT PROBLEMS.
WE WILL COME BACK TO THIS IN THE
MODERATED DISCUSSION AFTER THE
4TH TALK.
SHIFTING NO YOU TO ONE MORE AREA
OF DIFFERENT OUTCOMES WHERE
GLP-1S HAVE SIGNIFICANCE AND DR.
JENNIFER LUND WILL PRESENT AND
IS PROFESSOR OF EPIDEMIOLOGY AT
UNIVERSITY OF NORTH CAROLINA AT
CHAPEL HILL -- APPLICATIONS IN
CANCER, AGE THE ENVIRONMENT AND
WILL DISCUSS REAL WORLD
EFFECTIVENESS IN SAFETY
GLP-1-BASED THERAPIES AS THEY
RELATE TO CANCER.
DR. LUND?
>> THANK YOU VERY MUCH. SO I
WILL DIVE RIGHT ANY HAVE NO
RELEVANT DISCLOSURES AND
CONFLICTS OF INTEREST RELATED TO
PRESENTATION AND SEVERAL FUNDING
SOURCES ARE LISTED HERE. IN
THIS FINAL TALK OF THE SESSION I
WILL FOCUS ON UNIQUE
CONSIDERATIONS AND APPROACHES
REQUIRED WHEN WE ARE EVALUATING
EFFECTS OF GLP-1S ON RISK OF
CANCER AND PARTICULARLY USING
REAL WORLD DATA.
AS WE GET STARTED IT IS
IMPORTANT TO RECOGNIZE THAT
CANCER IS NOT A SINGLE
MONOLITHIC DISEASE BUT RATHER
COLLECTION OF HETEROGENOUS
CONDITIONS -- HAVE REALLY
GREATLY INCREASED KNOWLEDGE IN
UNDERSTANDING OF CANCER
ETIOLOGY.
SECOND, THERE ARE SEVERAL
POTENTIAL MECHANISMS EFFECTING
HOW GLP-1 INCREASE OR DECREASE
OF RISKS OF CANCER AND FOR
EXAMPLE IMPROVE METABOLIC
REGULATION AND DIRECT ANTITUMOR
EFFECTS CAN DECREASE CANCER RISK
AND IMMUNE MODULATION AND
EPIGENETIC CHANGES COULD
INCREASE OR DECREASE CANCER R
RISK.
TAKING THIS ALL TOGETHER THERE
IS GROWING EVIDENCE TO SUPPORT
GLP-1S MAY HAVE BOTH POTENTIAL
BENEFICIAL AND HARMFUL EFFECTS
RELATED TO CANCER. FOR EXAMPLE
SEVERAL STUDIES AND METAANALYSIS
SHOW GLP-1S REDUCE RISK OF
SEVERAL OBESITY RELATED CANCERS
AND SERIES OF SEPARATE STUDIES
SHOW THAT GLP-1S MAY BE
ASSOCIATED WITH INCREASED RISK
OF THYROID AND PARTICULARLY
MEDULLARY CANCER EVIDENCE FROM
ANIMAL MODEL SHOWING GLP-1S CAN
INCREASE THYROID PROLIFERATION
AND HYPERMRASHIA.
TO STUDY EFFECTS OF MEDICATIONS
LIKE GLP-1S ON RISK OF CANCER
RESEARCHERS HAVE TO UNDERSTAND
CARCINOGENESIS PROCESS AND HOW
MEDICATION EXPOSURES COULD ACT
AT VARIOUS POINTS IN THIS
PROCESS.
THIS KNOWLEDGE IS CRITICAL TO
HELP INFORM KEY DECISIONS AROUND
STUDY DESIGN AND ANALYSIS.
IN THIS FIGURE, DRUG A HERE IS
CONSIDERED TUMOR INITIALATOR OR
CAUSE OF FIRST CLONE OF
NEOPLASTIC CELLS AND DRUG B ALSO
SHOWN HERE IS A TUMOR PROMOTOR
OR DRUG THAT CAN ACCELERATE
PROGRESSION OR GROWTH OF
MALIGNANT OR SUBCLINICAL DISEASE
AND HYPOTHESIS WHERE DRUG MAY
ACT ALONG IT PROCESS HAS
IMPLICATIONS FOR POTENTIAL
LENGTH OF EXPOSURE REQUIRING FOR
CLINICALLY RELEVANT EFFECTS ON
CANCER RISK AND WHEN WE REFER TO
AS INDUCTION PERIOD AND FOR
DURATION OF FOLLOW UP THAT IS
REQUIRED TO BE ABLE TO DETECT
CLINICALLY SIGNIFICANT
MALIGNANCIES FOR LATENT PERIODS.
WHILE THERE IS OFTEN NOT ENOUGH
KNOWN ABOUT A DRUG'S MECHANISM
TO UNDERSTAND WHETHER IT IS AN
INITIALATOR OR PROMOTER OR WHAT
REVELIANANT INDUCTION PERIODS
ARE HAVING LONG TERM DATA ON
DRUG EXPOSURES AND FOLLOW UP
ALLOW RESEARCHERS TO MAKE
DIFFERENT ASSUMPTIONS ABOUT
DIFFERENT RELEVANT EXPOSURE
PERIODS.
SO WITH THESE IMPORTANT
CONSIDERATIONS IN MIND, WE CAN
NOW REVIEW SOME EVIDENCE ON
GLP-1S IN CANCER RISK AND HOW TO
BEST LEVERAGE REAL WORLD DATA TO
FURTHER EXPAND ON EVIDENCE BASE.
SO THERE IS SEVERAL TRIALS THAT
HAVE BEEN META-ANALYZED TO
EVALUATE EFFECTS OF GLP-1S ON
RISK OF SPECIFIC CANCER TYPES
AND HERE I HIGHLIGHTED THREE
METAANALYSIS IN THYROID AND
BREAST CANCER AND LARGEST EFFECT
SIZE IN MAGNITUDE IS FOR THYROID
CANCER AND HOWEVER THERE ARE
SEVERAL WILL IMITATIONS TO
METAANALYSIS FOR TRIALS FOR
UNDERSTANDING EFFECTS OF GLP-1S
ON CANCER RISK AND FIRST
EVIDENCE IS LARGELY DERIVED FROM
PATIENTS WITH TYPE 2 DIABETES
AND LESS CLINICAL EVIDENCE AND
CONTEXT FROM OBESITY SETTING
AND TRIALS HAVE SHORT FOLLOW UP
AND ESTIMATES CAN'T BE
EXTRAPOLATED TO LONGER TERM
EFFECTS AND OUTCOMES ARE RARE IN
TRIALS AND WITH POOLING ACROSS
TRIALS, ESTIMATES ARE INPRECISE.
FINALLY, BECAUSE OF FOCUS OF
TRIALS HAS NOT BEEN ON CANCER AS
AN OUTCOME OF INTEREST THERE IS
OFTEN NO SUBDATYPE DATA THAT IS
COLLECTED AND OFTEN NECESSARY
AND RESULT RESEARCHERS ARE
INCREASING WILL I TURNING
TOWARDS REAL WORLD DATA STUDYING
EFFECTS ON GLP-1S RISK AND
NUMBER OF STUDIES EVALUATING
ASSOCIATIONS EXPONENTIALLY HAS
GROWN IN THE PAST FEW YEARS AND
OVERALL MOST OF THE STUDIES USE
COMMON DATA SOURCES OF REAL
WORLD DATE AINCLUDING ELECTRONIC
HEALTH RECORDS AND
ADMINISTRATIVE AND INSURANCE
CLAIMS DATA AND OBVIOUSLY DATA
SOURCES HAVE THEIR OWN DISTINCT
STRENGTHS AND LIMITATIONS MANY
OF WHICH HAVE BEEN MENTIONED
TODAY AND WILL FOCUS ON THOSE
RELATED TO STUDYING GLP-1S AND
CANCER RISK AND FIRST
ADMINISTRATIVE DATA TEND TO
CAPTURE LARGE BROAD POPULATIONS
CONTAINING GRANULAR LONGITUDINAL
DRUG EXPOSURE NEEDED FOR STUDIES
AND CAPTURE CARE DELIVERED
ACROSS HEALTH CARE SYSTEMS.
HOWEVER, IN CONTEXT CLAIMS DATA
IS OFTEN LIMITED IN INFORMATION
IN CLINICAL INDICATION FOR
GLP-1S AND ALSO SPECIFIC
SUBTYPES OF CANCER THAT WE MAY
BE INTERESTED IN STUDYING.
ON THE OTHER HAND AS WE HAVE
HEARD BEFORE ELECTRONIC HEALTH
RECORDS ARE ABLE TO CAPTURE
GRANULAR CLINICAL DATA OFTEN ON
INDICATION OF TREATMENT AND MORE
CLINICALLY RELEVANT INFORMATION
ON CANCER AND HOWEVER THEY
FREQUENTLY LACK LONGITUDINAL
DRUG EXPOSURE IN DISPENSING DATA
AND MIGHT HAVE A HIGH DEGREE OF
MISSINGNESS OF KEY VARIABLES AND
AGAIN IS CONCERN ABOUT
OBSERVABILITY WHEN CARE IS
DELIVERED OUTSIDE OF CAPTURE OF
A GIVEN HEALTH CARE SYSTEM.
FINALLY, WHAT WE WILL TOUCH ON
IS PATIENT REGISTRIES THAT ARE
OFTEN MANDATED TO COLLECT
STRUCTURED CANCER DATA INCLUDING
HISTOLOGY AND HAVE POTENTIAL TO
BE LINKED TO SOURCES OF DRUG
DISPENSING AND CLINICAL
INFORMATION AND HOWEVER DATA IS
LIMITED IN SAMPLE SIZE AND
INJURE DICTIONS THAT COLLECT
INFORMATION MIGHT NOT BE NAMELY
LARGED FOR EXAMPLE EXTANDIN
AFIAN COUNTRIES HAVE THIS TYPE
OF DATA AND BECAUSE OF THAT
MIGHT BE DIFFERENCED IN CARE
DMRIFRY HAM PPERING POTENTIAL
GENERALIZABILITY TO US CONTEXT
AND BEYOND THINKING ABOUT
FITNESS OF DATA STUDYING EFFECTS
OF GLP-1S AND CANCER RISK WE CAN
THINK CLEARLY ABOUT HOW TO
DESIGN AN OBSERVATIONAL STUDY TO
AVOID COMMON PITFALLS IMMORTAL
TIME BIAS AND SELECTION BIAS
THAT SPEAKERS REITERATED AND SAW
IN WORKSHOP USEFUL IN HELPING
RESEARCHERS SPECIFY PROTOCOL OF
RANDOMIZED PRAGMATIC TRIAL TO
ANSWER CALLS OF QUESTION OF
INTEREST AND WHEN WE CALL TARGET
TRIAL AND SECOND IT HELPS
RESEARCHERS USE OBSERVATIONAL
DATA TO ATTEMPT TO EMULATE THIS
TRIAL AND COMPONENTS OF TARGET
TRIAL INCLUDE ELIGIBILITY
CRITERIA TREATMENT STRATEGIES
ASSIGNMENT PROCEDURES FOLLOW UP
OUTCOMES AND CAUSAL CONTRAST AND
DATA ANALYSIS AND FOR PURPOSES
OF DURATION OF THIS PRESENTATION
I WILL WALK THROUGH A SPECIFIC
STUDY FROM THESE AND DISCUSS
EACH OF THE COMPONENTS WITH
SPECIFIC CONSIDERATION OF
STUDYING CANCER AS AN OUTCOME OF
PRIMARY INTEREST.
STUD YAY THAT I WILL FOCUS ON IS
A RECENT PUBLICATION BY PASTOR
KNACKIN AND COLLEAGUES PUBLISHED
IN DECEMBER OF 2024
MULTI-COUNTRY DATA BASE STUDY
USING PATIENT REGISTRIES FROM
DENMARK NORWAY AND SWEDEN
INCLUDING INITIATORS WITH GLP-1S
AND DPP INHIBITORS IN DIABETES
CONTEXT AND OUTCOME OF INTEREST
IS THYROID CANCER AND
INDIVIDUALED FOLLOWED IN
DATABASES AVERAGE OF FOUR YEARS
IN GLP-1 GROUP AND 5.1 YEARS IN
DPP4 INHIBITOR GROUP AND OVERALL
AUTHORS REPORTED THAT INITIATION
OF GLP-1S VERSUS DPP4 INHIBITOR
NOZ THE ASSOCIATED WITH
INCREASED RISK OF THYROID CANCER
OR MEDULLARY THYROID CANCER AND
WAS A WELL-DONE STUDY AND CAN
USE IT TO HIGHLIGHT SPECIFIC
COMPONENTS OF TARGET TRIAL MORE
BROADLY AND TALK ABOUT
EXTENSIONS TO OTHER FORMS OF
REAL-WORLD DATA.
SO THE FIRST COMPONENT IS
ELIGIBILITY.
SO WHAT WE ARE TRYING TO DO IS
FIGURE OUT WHO WILL BE IN THE
STUDY.
WHEN FOCUSED ON STUDYING
HIGHROID CANCERS AND OUTCOME WE
HAVE TO FIRST ENSURE THAT PEOPLE
IN THE TRIAL HAVE NOT PREVIOUSLY
HAD THYROID CANCER AND MAY
CONSIDER EXCLUDING INDIVIDUALS
RECENTLY DIAGNOSED WITH ANOTHER
CANCER THAT MAY UNDERGO ACTIVE
CANCER AND TREATMENT AND THIRD
MAY CONSIDER ALSO EXCLUDING
INDIVIDUALS WITH CERTAIN
HERITABLE SYNDROMES VASTLY
INCREASING RISK OF THYROID
CANCER AND IN TERMS OF EMULATING
CRITERIA USING PATIENT ARE
EDGETRY DATA PASTER KNACK STUDY
WAS ABLE TO LEVERAGE CANCER
REGISTRY DATA TO EXCLUDE THOSE
WITH PRIOR HISTORY OF THYROID
CANCER AND THOSE DIAGNOSED IN
THE PAST YEAR AND FURTHERMORE
USED MEDICAL ARE EDGE STRERS TO
EXCLUDE INDIVIDUALS WITH
SPECIFIC -- ASSOCIATED WITH
THOIROID CANCER AND THINKING OF
SOURCES OF REAL WORLD DATA LIKE
EHRS AND CLAIMS WE MIGHT
CONSIDER WHETHER IT IS FEASIBLE
TO LINK CANCER TO SAME EXCLUSION
CRITERIA AND IF NOT POSSIBLE
VALIDATION STUDIES FOR
ALGORITHMS APPLIED WITHIN
RESOURCES ARE NEEDED AND WE NEED
TO ATHAT THOSE ALGORITHMS ARE
APPLICABLE TO TARGET POPULATION
OF INTEREST.
SO THE SECOND COMPONENT ARE
TREATMENT STRATEGIES AND
EMULATION AND SOLET PASTER KNACK
STU
STUDY.
ALSO CAPTURE INFORMATION ON BUY
DEETIES MEDICATIONS AND
COMPLICATIONS AND RELEVANT
MORBID CONDITIONS CONSIDERING
REAL WORLD DATA SOURCES WE HAVE
TO THINK OF COMPLETENESS AND
ACCUR
ACCURACY.
SCREENING PATTERNS THAT MAY LEAD
TO EARLIER DETECTION IN ONE
GROUP VERSUS ANOTHER.
FINALLY 4TH COMPONENT OF FOLLOW
UP STARTING IT AT DRUG
INITIATION AND CONTINUE AND
EARLIER OF FOLLOWING EVENTS AND
THYROID CANCER AND DEATH OR 10
YEARS OF FOLLOW UP AND PASTER
KNACK STUDY FOLLOWED A SIMILAR
STRATEGY? EMULATION AND
CONSIDERED EMMI [GROUP
PRESENTATION] FROM COUNTRIES OF
INTEREST AS A CENSORING EVENT.
WHEN WE THINK ABOUT FOLLOW UP
AND REAL WORLD DATA SOURCES
THERE IS LOTS OF VARIATION IN
DURATION OF FOLLOW UP BY PAYER
WITH TYPICALLY LONGER PERIODS OF
CONTINUOUS ENROLLMENT OF
MEDICARE ELIGIBLE POPULATIONS
COMPARED WITH COMMERCIALLY
ENSURED POPULATIONS AND E HAD.
R WE ARE CONCERNED ABOUT
OBSERVABILITY ISSUES AND NEED TO
CENSOR INDIVIDUALS WHEN
FOLLOWING UP AND BECAUSE OF
CONCERNS, AGAIN, AROUND RELEVANT
INDUCTION PERIODS RESEARCHERS
INCLUDING PASTER KNACK AND
COLLEAGUES FREQUENTLY EXAMINED
RISK OF CANCER EARLY IN THE
FOLLOW UP PERIOD AND UNLIKELY
THAT EARLY CANCERS ARE DUE TO
EFFECT OF THE DRUG AND IN
ADDITION AUTHORS WILL WANT
IMPLEMENT A SERIES OF
SENSITIVITY ANALYSIS THAT USE
DIFFERENT LAG TIMES WHERE PRIOR
TO THE END OF THE LAG TIME
CANCERS ARE ACTUALLY NOT
ATTRIBUTED TO THE EXPOSURE GROUP
AND THIS CAN HELP PROVIDE SOME
BOUNDS OF AROUND HOW DIFFERENT
ASUCTIONS OF INDUCTION AND
LATENT PERIODS CAN ACTUALLY
EFFECT TREATMENT ESTIMATES.
SO IN TERMS OF IDENTIFYING THE
OUTCOME TARGET TRIAL TYPICALLY
IN A PRAGMATIC SETTING MAY
REQUIRE SELF-PURPORTED CANCER
DOOIGNOSIS WITH SUBSEQUENT
DOCUMENTATION AND IN PASTER
KNACK STUDY THEY WERE ABLE TO
IDENTIFY THYROID CANCER USING
NATIONWIDE CANCER ARE EDGETRIES
THAT INCLUDE DETAILED TUMOR
INFORMATION. SIMILAR AS IN
PRIOR COMPONENTS IF STUDIES RELY
ON REAL WORLD DATA ON ALGORITHMS
THEY HAVE TO BE VALIDATED IN
TARGET POPULATION OF INTEREST
AND POTENTIALLY NEED TO CONSIDER
DOING SOME BIAS ANALYSIS WHERE
IT MIGHT BE WARRANTED.
AGAIN, BROAD CONSIDERATIONS
AROUND LINKAGIN INCIDENT CANCER
TO REGISTRIES IS IMPORTANT TO
CONSIDER AND SECOND THING IS
CAUSAL CONTRAST AND THERE HAS
BEEN DISCUSSION AROUND
ESTIMATING INTENTION TO TREAT
AND PRO PROTOCOL EFFECTS AND
PASTER KNACK STUDY AND EMULATION
THEY EVALUATED OBSERVATIONAL
ANALOGUE IN ATTENTION TO TREAT
EFFECT AND TREATED ANALYSIS THEY
CENSORED AND WEIGHTED
INDIVIDUALS THAT DISCONTINUED OR
SWITCHED AND THINKING OF OTHER
SOURCES OF REAL WORLD DATA EHRS
DON'T HAVE ACCESS TO
LONGITUDINAL DATA AND THUS MAY
NOT BE USED FOR AS TREATED OR
PROPROPOE COLANALYSIS AND
IMPORTANT CONSIDERATION IS REAL
WORLD DATA MAY NOT CONTAIN ALL
INFORMATION ON TIME VARYING
CONFOUNDERS NEEDED TO ESTIMATE
APPROPRIATE CENSORING LINKS.
AS WAS DISCUSSED FOR SWITCHING
IS COMMON IN SETTING OF TYPE 2
DIABETES -- GLP-1S ONG CANCER
AND DONG BY PASTER KNACK AND
COLLEAGUES IT IS IMPORTANT TO
PLOT CUMULATIVE RISK CURVES FOR
CANCER OVER TIME AND CONSIDER
ACCOUNTING FOR OTHER COMPETING
EVENTS LIKE DEATH USING
APPROPRIATE ESTIMATORS.
SO I THINK TO WRAP UP IN SUMMARY
USING REAL WORLD DATA EVALUATING
EFFECTS OF GLP-1S ON CANCER WE
HAVE TO RECOGNIZE THAT CANCER IS
HETEROGENOUS DISEASE STUDYING
MEANINGFUL SUBTYPES AND FOLLOW
UP FOR STUDIES WITH SHORT TERM
FOLLOW UP AND NEED ENSURE THAT
OUR STUDIES ARE USING VALIDATED
ALGORITHMS FOR KEY VARIABLES AND
THEY ARE RELEVANT TO TARGET
POPULATIONS OF INTEREST AND WE
NEED TO BE VERY CLEAR ABOUT
TRADEOFFS ESTIMATING DIFFERENT
CAUSAL CONTRASTS AND BEGIN IS
NICELY DISCUSSED EARLIER IN THE
SESSION. FINALLY, SPECIFIC TO
CANCER IT IS A RARE OUTCOME OF
THIS ESTIMATING ADVERSE RISKS
AND PUTTING RISK IN CONTEXT OF
BENEFITS OF THERAPY.
SO IN THINKING ABOUT WHETHER
PRAGMATIC TRIALS ARE NEEDED,
FIRST THING WE NEED TO THINK
ABOUT IS WHO WOULD BE ELIGIBLE
FOR A TRIAL LOOKING AT A CANCER
OUTCOME AND HAS TO BE IN A VERY
LARGE TRIAL WITH LONG TERM
FOLLOW UP POTENTIALLY IN
ENROLLING HIGH RISK POPULATIONS
IN OLDER ADULTS AND NEED TO
THINK ABOUT AGAIN ABOUT WHAT
IMPORTANT TREATMENT STRATEGIES
IN COMPARATORS WOULD BE AND THEN
I THINK THIS IS AN IMPORTANT
POINT IF WE WANT TO CONDUCT A
LARGE LONG TERM PRAGMATIC TRIAL
LINKING DATA TO CANCER
REGISTRIES POTENTIALLY THROUGH
THE VIRTUAL POOLED ARE EDGETRY
OR CANCER LINKAGE SYSTEM THAT
WOULD BE A RELEVANT WAY TO DO
THIS AT A MORE PRAGMATIC SCALE
AND TO NOTE, BRITISH DOCTORS
ASPIRIN TRIAL AND ANOTHER TRIAL
IN UK HAVE DONE THIS AND THEY
WERE STUDYING CARDIOVASCULAR
OUTCOMES AND WERE ATOIBL LINK
AND FOLLOW PEOPLE OVER 20 YEARS
TO LOOK AT COLORECTAL CANCER
INCIDENTS AS AN OUTCOME AND IN
THE FINAL KIND OF PIECE HERE,
THERE ARE SEVERAL GAPS IN AREAS
FOR FUTURE RESEARCH AND FIRST
RESEARCHERS ARE LARGELY
CONDUCTING CASE CONTROL AND
COHORT STUDIES EVALUATING
EFFECTS OF GLP-1S ON CANCER
RISKS AND OTHER DESIGNS SHOULD
BE REQUIRED REQUIRING DIFFERENT
ASSUMPTIONS RELYING RESEARCH
COMMUNITY TO TRIANGULATE
EVIDENCE AND GENERATE OBSERVED
SUPPORT FOR FINDINGS AND SECOND
DONE BY PASTER KNACK SHOULD
CONSIDER POSSIBILITY OF
CONDUCTING MULTINATIONAL DATA
BASE STUDIES THAT ARE
INCREASINGLY POSSIBLE WITH
ADOPTION OF COMMON DATA MODELS
AND POWERFUL TOOL TO STUDY RARE
OUTCOMES LIKE CANCER AND THIRD
THE RESEARCH COMMUNITY NEEDS TO
INVEST IN SUPPORT LARGE SCALE
LINKAGE EFFORTS BETWEEN REAL
WORLD DATA LINKING EHRS AND
CENTRAL ARE EDGETRY DATA AND
ONGOING EFFORTS N3C AND CANCER
REGISTRIES AND LINKAGE WITH
MEDICARE AND MEDICAID CLAIMS
DATA AND FINALLY, BECAUSE CANCER
IS SUCH A RARE OUTCOME THERE IS
AN URGENT NEED TO CONTEXTUALIZE
EVIDENCE GENERATED FROM REAL
WORLD DATA INTO CONTEXT OF
BENEFITS OF MEDICATIONS AND
IMPROVED APPROACHES FOR PATIENT
PROVIDER COMMUNICATION AROUND
TRADEOFFS ARE NEEDED.
I THINK THAT IS IT FOR ME AND
WOULD LIKE TO THANK COLLEAGUES
AT UNC AND NORTH CAROLINA
DIABETES RESEARCH CENTER AND DR.
HILL AND OTHER ORGANIZERS AND
LOOKING FORWARD TO OUR UPCOMING
DISCUSSION. THANK YOU.
>> THANK YOU FOR THE GREAT TOUR
IN GLP-1 AND CANCER SITUATION.
SO IT IS NOW 1228 AND I WILL
JUST INVITE THE PANELISTS TO ALL
TURN THEIR CAMERAS BACK ON.
I WILL DOUBLE CHECK WE HAVE
UNTIL 12:45 FOR THE DISCUSSION
AND WILL ADJUST THE TIME LINE A
BIT AND IF YOU ARE HERE AND CAN
TURN THE CAMERA BACK ON THAT
WOULD BE GREAT.
WE CAN GO AHEAD AND START TO
TALK THROUGH QUESTIONS THAT CAME
UP.
DR. MCCOY, I WILL GO TO YOU
FIRST WITH A QUESTION THAT CAME
IN THROUGH THE CHAT.
DO YOU HAVE ANY THOUGHTS HOW TO
APPLY CKM REAL-WORLD DATA
OUTCOMES MEASURES IN PEDIATRICS
AND IN PARTICULAR I BELIEVE THAT
THE QUESTION IS FOCUSED ON THE
IDEA THAT YOU HAVE CHILDREN AND
YOU DON'T ACTUALLY GET HARD
OUTCOMES OR DON'T GET THEM AS
OFTEN AND THERE COULD BE
INTERMEDIATE MEASURES AND, YOU
KNOW, HOW -- WHAT SORT OF ADVICE
AND THOUGHTS WOULD YOU HAVE TO
SHARE ABOUT HOW TO THINK ABOUT
THESE ISSUES IN THE PEDIATRIC
SETTING?
>> I THINK THAT IS A REALLY
IMPORTANT POINT.
I THINK IT ALSO UNDERSCORES
IMPORTANCE OF REAL WORLD DATA TO
STUDY MEDICATION USE IN YOUTH.
THEY ARE OFTEN MAYBE USED OFF
LABEL AND SCARCITY OF CLINICAL
TRIAL DATA IN THIS POPULATION.
SO I THINK, YOU KNOW, THE
BIGGEST QUESTION THAT CAME UP
THROUGHOUT THE TALKS IS LATE NRC
PERIOD BETWEEN HARD OUTCOME AND
TREATMENT EXPOSURE AND DEPENDING
ON SPECIFIC OUTCOME YOU ARE
INTERESTED IN YOU MAY SEE HARD
OUTCOMES IN YOUTH. YOU KNOW?
THE OTHER IS LOOKING FOR DATA
ASSETS THAT ARE GOING TO HAVE
VARIABLES THAT YOU NEED TO
ASCERTAIN THE SPECIFIC QUESTION
WHETHER YOU ARE LOOKING AT
WEIGHT, GLIESEMIA, YOU KNOW,
PROGRESSION OF KIDNEY DISEASE,
ET CETERA.
THINK ELECTRONIC HEALTH RECORD
DATA AND EHR THAT IS LINKED TO
CLAIMS THAT ARE DEFINITELY
ADEQUATE FOR THIS. I THINK THE
BIGGEST CHALLENGE COMING TO
YOUTH AND MEDICATIONS THAT IS
APPROPRIATELY CLASSIFYING
DIABETES TYPE.
ESPECIALLY THERE IS YOUTH WITH
OBESITY BY ITSELF AND COMING TO
DIABETES, I THINK THAT BECOMES A
LITTLE MORE CHALLENGING TO FULLY
KIND OF PHENOTYPE THE DIABETES
TYPE ESPECIALLY WHEN BOTH TYPE 1
AND 2 PRESENT AT SAME TIME AND
HAS TO BE CONSIDERATIONS DONE TO
KNOW EXACTLY THE POPULATION YOU
ARE STUDYING.
I DON'T THINK FOR YOUTH THE
CONSIDERATIONS ARE ANY DIFFERENT
THAN FOR ADULTS OTHER THAN WE
NEED REAL WORLD DATA EVEN MORE
FOR THAT POPULATION I THINK.
>> REALLY EXCELLENT POINTS AND
LOVE HOW THE TALKS PICKED UP ON
LOTS OF THEMES BROUGHT UP IN THE
PLENARY AND UNPACK THEM IN
SPECIALIZED SETTINGS AND IS A
COUPLE ISSUES YOU ALSO ALL
TOUCHED ON AND DID -- I WOULD
LOVE IT IF YOU COULD UNPACK THEM
A LITTLE MORE AND ONE IS A
QUESTION OF DATA LINKAGE AND
THERE WERE A COUPLE OF EXAMPLES
WHERE EHR AND CLAIMS DATA WERE
LINKED SORT OF THAT WE SAW
FLYING BY. I WANTED TO EACH
GIVE YOU AN OPPORTUNITY TO
ADDRESS THAT QUESTION
SPECIFICALLY. DO YOU -- DO YOU
-- WHAT DO YOU -- WHAT DO YOU
THINK ABOUT THE LINKAGE OF EHR
CLAIMS DATA OR REGISTRY DATA AND
ARE THERE KEY EXAMPLES AND/OR DO
YOU HAVE KEY RESOURCES THAT YOU
THINK THAT THE AUDIENCE SHOULD
BE AWARE OF?
>> I'M HAPPY TO START SINCE I
KIND OF WAS THE LAST ONE TO
MENTION LINKAGE.
I THINK IN THE CONTEXT OF
CANCER, PROBABLY MOST VALUABLE
LINKAGE TO GET TO THE CANCER
REGISTRY IS WHERE THE MOST
DETAILED GRANULAR INFORMATION
ABOUT THE CANCER IS AND WHEN WE
REALLY WANT TO UNDERSTAND KIND
OF THESE SPECIFIC EFFECTS, I
THINK THAT IS THE LEVEL OF
GRANULARITY WE ARE TRYING TO GET
TO AND GOOD NEWS IS I THINK
THERE ARE REALLY MORE EFFORTS
PUSHING TOWARDS TRYING TO LINK
SOME OF THE LARGE-SCALE EHR
SYSTEMS AND ONE I MENTIONED WAS
N3C COLLABORATIVE THAT IS SET UP
BECAUSE OF COVID.
NOW THEY ARE TRYING TO KEEP
INFRASTRUCTURE AND USE IT TO
BRING IN OTHER USE CASES.
I KNOW THERE IS A BIG PUSH RIGHT
NOW ONGOING AND UNC IS INVOLVED
WITH THIS IN TERMS OF LINKING
DATA TO CR REGISTRY DATA AND
CLAIMS DATA LIKE MEDICARE.
I THINK THAT IS THE TYPE OF RESO
URS TH -- RESOURCE I THINK WOUL
REALLY HELP MOVE THIS LINE OF
WORK FORD.
>> IT IS SO IMPORTANT. SORRY GO
AHEAD, DR. MCCOY.
>> SO SORRY AND COMPLETELY AGREE
AND ONE THING TO NOTE IN
RELATION TO PREVIOUS QUESTION
RAISED IN PEDIATRICS THAT I
THINK LINKAGES ARE ESPECIALLY
FOR POPULATION AND COMMONLY WHEN
YOU LOOK AT CLAIMS PEOPLE USE
MEDICARE AND THAT IS WHAT IS
AVAILABLE NATIONALLY AND FOCUSES
ON OLDER ADULTS AND WE HAVE VERY
LITTLE LINKABLE INFORMATION FOR
YOUTH AND YOUNG ADULTS AND
MEDICATIVE DATA IS VERY
CHALLENGING TO ACCESS AND LINK
TO OTHER SOURCES AND REGULATORY
ISSUES SURROUNDING MEDICAID AND
OTHER CONSIDERATION OF BUILDING
AGAIN ON THAT, IT IS
SELF-ENSURED ORGANIZATIONS AND
HMOS AND KAISER IS VERY -- AND
VA AND THOSE ARE POWERFUL LINKED
DATA ASSETS BUT FOR KIND OF
SPECIFIC PATIENT POPULATION.
AGAIN, VA WON'T HAVE MUCH OR
ANYTHING FOR YOUTH.
OR FOR YOUNGER ADULTS WITH
CHRONIC HEALTH CONDITIONS AND
HAVE TO WAIT FOR VETERANS TO AID
AND DEVELOP THOSE AND SPEAKING
TO, ONE, IMPORTANCE OF INVESTING
IN DATA RESOURCES AND DREAM
WORLD AND INTO DOING THE STUDIES
IN DIFFERENT POPULATIONS.
I THINK IT IS ESPECIALLY, YOU
KNOW, CALL HERE TO NIDDK THAT
FUNDERS THAT SOMETIMES
DUPLICATION AND REPLICATION
EFFORTS IF DONE IN DIFFERENT
POPULATIONS AND USING DATA
ASSETS ARE CRITICAL MAY NOT BE
AS INNOVATIVE AND THINK THEY ARE
CRITICALLY IMPORTANT TO GET
ANSWERS FOR, YOU KNOW, DIFFERENT
POPULATIONS THAT WE CARE FOR.
AND ENDING WITH ANOTHER PLUG FOR
WHY -- FOR OUR FUNDERS AND LOTS
OF DATA ASSETS ARE VERY
EXPENSIVE ALSO.
THAT I THINK LIMITS ABILITY TO
DO THIS WORK AND WITH DATA I
WORK WITH OPTUM LABS THAT
INCLUDED ELECTRONIC HEALTH
RECORDS LABS AND CLAIMS. IT IS
ALSO LINKED TO CR REGISTRIES AND
OTHER REGISTRIES AND IS VERY
EXPENSIVE AND OFTEN IS AN
ASSUMPTION THAT REAL WORLD DATA
STUDIES ARE ACHIEVED AND CAN BE
DONE WITH LITTLE RESOURCES THAT
I THINK I WISH IT WAS THE CASE
AND THINK JUST COST AND TIME
REQUIRED TO DO LINKAGES OR BUY
THEM AS SUBSTANTIAL.
>> YEAH. WELL STATED.
>> THAT REALLY GREAT POINTS AND
I JUST WANTED TO ADD BECAUSE OF
MENTION OF INTEGRATED HEALTH
CARE SYSTEMS AND IN KAISER
PERMANENTE, WE ARE ABLE TO PULL
IN CLAIMS DATA AND LINK IT
SEAMLESSLY IN OUR ANALYSIS.
IN KAISER PERMANENTE AND IN OUR
PARTICULAR RE REGION OR CALLE W
HAVE TO LINK UP PARTNERS AND
BRING DATA TOGETHER AND AGREE IT
IS DISPENSESIVE REQUIRING
SUPPORTS AND ILLUSTRATING AN
EXAMPLE WE -- COLLEAGUES AND I
HAVE BEEN PARTICIPANTS IN MENTAL
HEALTH RESEARCH NETWORK
CONSORTIUM FUNDED FOR SEVERAL
CYCLES BY NIMH AND HAS BEEN AN
EXTREMELY PRODUCTIVE GROUP OF
PEOPLE THAT ALLOWED US TO DO
FEDERATED ANALYSIS WHERE
ANALYSIS HAVE BEEN DISTRIBUTED
ACROSS THE DIFFERENT HEALTH
SYSTEMS AND WE HAVE ALSO BEEN
ABLE IN LOTS OF PROJECTS TO POOL
DATA TOGETHER AND DO HIGHER
IMPACT WORK. BUT THAT, YOU
KNOW, MECHANISM AND WONDERFULLY
SUPPORTED NETWORK HAS BEEN
PHASED OUT AND NOW, YOU KNOW, WE
ARE KEEPING THINGS GOING THROUGH
OUR SORT OF VOLUNTEER AND, YOU
KNOW, FOR AMICABLE RELATIONSHIPS
WITH EACH OTHER AND FOR REAL
WORLD DATA WE NEED TO SUPPORT
CONSORTIA. SOME OUTCOMES ARE
VERY RARE AND REQUIRE A LOT OF
DATA AND WE WANT TO BE ABLE TO
REPLICATE AND BE GENERALIZABLE
ACROSS THE WHOLE POPULATION.
>> RIGHT. RIGHT. YEAH. SO
REAL WORLD DATA SEEMS LIKE SO
MUCH DATA.
SOMETIMES YOU KNOW MORE THAN ONE
HEALTH SYSTEM IS REALLY
IMPORTANT.
YOU ARE -- YOU CITED ANALYSIS
WHICH HAD DATA FROM MULTIPLE
INTEGRATED HEALTH SYSTEMS AS ONE
APPROACH.
>> RIGHT.
>> SOMEBODY PUT IN CHAT MORE
ABOUT N3C LINKAGES AND KNOW
THERE ARE SITES IN PCORI THAT
ARE TRYING TO IMPROVE ACCESS TO
CLAIMS DATA AND AREA THAT COULD
USE MORE FOCUS DEFINITELY.
SO A SECOND METHODS ISSUE
TOUCHED ON IN MULTIPLE TALKS IS
IDEA OF HOW YOU ACCURATELY
IDENTIFY YOUR COHORT AND HOW
IMPORTANT IT IS. IT WAS
SOMETHING THAT WAS SORT OF JUST
SORT OF AN ASIDE AND THINK THAT
ALL FOUR PRESENTATIONS AND KNOW
WE HAVE SOME PEOPLE ON THE CALL
HERE WHO HAVE NOT WORKED MUCH
WITH REAL WORLD DATA IN THE PAST
AND WONDER IF THEY CAN ESTIMATE
HOW -- WHAT A TASK THAT IS TO
BUILD INTO PROJECT AND WONDER IF
YOU CAN SHARE A LITTLE ABOUT
YOUR APPROACH FOR MAKING SURE
THAT YOU USE BEST APPROACH TO
IDENTIFY YOUR COHORT.
>> SO I THINK I CAN START. IN
OUR DOCUMENT STUDIES WE HAVE TWO
COHORTS GENERALLY ONE IS TYPE 2
DIABETES COHORTS AND GLP-1
ACTIVE COMPARATORS WOULD BE THE
SECOND LINE AND OTHER SECOND
LINE INTERACTS SOMETIMES
INDIVIDUAL DRUG LIKE TPP4 AND
SDL2 CLUSTERED DRUGS AND IN THIS
COHORT WE -- WE ALWAYS DO DOUBLE
-- IN THAT COHORT COMPLETELY
OVERWEIGHT OBESITY COHORT AND
SOMETIMES WE STRUGGLE WHETHER
COHORT WE SHOULD INCLUDE
PATIENTS WITH DIABETES AND
INCLUDE PATIENTS WITH DIABETES
ANYWAY FOR ISSUES AND LOTS OF
PEOPLE REALLY YOU CANNOT
SEPARATE PATIENTS WITH
SUBOPTIMAL METABOLIC PROFILE AND
IN THAT COHORT WE USE GLP-1 AS
TREATMENT AND COMPARATOR ALWAYS
NOW USERS IN -- SO IT WAS MORE
LIKE RIGOROUS FOR PROPENSITY
SCORE APPROACH TO TRY TO
MITIGATE CONFOUNDING BY
INDICATION. YEAH A QUESTION
CALLED OUT TO YOU IF DOG REAL
WORLD DATA STUDY AND BEST
PRACTICES YOU MIGHT SUGGEST
USING CANCER CODES AND OTHER
AVENUES.
>> GREAT ONE AND EVERYONE USING
CLAIMS WRESTLES WITH TWO PIECES
OF IT, PIECE THAT YOU WANT TO --
ONCE YOU IDENTIFY INITIATORS OF
DRUGS OF INTEREST YOU NEED TO
LOOK BACK AND MAKE SURE PEOPLE
DON'T HAVE CANCER YOU WILL STUDY
AND YOU NEED TO LOOK BACK AND WE
TEND TO USE DIFFERENT ALGORITHMS
THAT ARE -- YOU KNOW, WE
BASICALLY HAVE A VERY HIGH PPV
AND LIKE YOU ARE NOT GOING TO
GET A LOT OF FALSE POSITIVES AND
PEOPLE IN THERE TRULY HAVE
CANCER AND YOU TRY TO GET RID OF
PEOPLE AT BASELINE TO MAKE SURE
YOU ARE TRULY LOOKING AT
INCIDENT DISEASE GOING FORWARD
AND THINK THAT IS THE IMPORTANT
POINT TO WASH OUT YOU USE A
DIFFERENT ALGORITHM THAN YOU
MIGHT USE WHEN LOOKING AT
INCIDENT CANCER.
SO THERE IS A LOT OF ALGORITHMS
THAT HAVE BEEN VALIDATED THAT
USE 2 PLUS DIAGNOSIS WITHIN 60
DAYS AND TRICK ABOUT SOME OF
THESE WHEN YOU ACTUALLY
IMPLEMENT THEM IS THEY REQUIRE
YOU TO LOOK FORWARD IN TIME AND
COME UP AND WE GET INTO TRICKY
THINGS AROUND LOOKING FORWARD TO
DEFINING SOMETHING AND WHERE YOU
ACTUALLY CALL A CANCER A CANCER.
SO I THINK THAT EVERYONE, YEAH,
WE NEED TO BE MINDFUL. THERE IS
STILL ROOM HERE FOR IMPROVING
SOME ALGORITHMS FOR DEFINING
THESE OUTCOMES USING ICD CODES
AND OTHER RELATED INFORMATION
LIKE TREATMENTS AND LAB DATA IF
POSSIBLE AS WELL.
>> GREAT. THANK YOU. DR.,
THERE IS A QUESTION RELATED TO
CLASSIFYING AS WELL FOR YOU HOW
ACCURATE REAL WORLD DATA SOURCES
IN CLASSIFYING ADDICTION EATING
DISORDERS AND SUICIDALITY AND
HOW DO YOU DEAL WITH THIS?
>> YEAH. I MEAN, I THINK
SIMILAR CONSIDERATIONS DR. LUND
OUTLINED APPLY HERE AND WILL
GIVE EXAMPLES AND SIMILARLY
THINK OF DIAGNOSIS AS BEING NOT
SO SENSITIVE BUT VERY SPECIFIC.
IT TAKES AN EXPERIENCE WITH THE
DATA TO KNOW WHAT TO EXPECT AND
WHAT KINDS OF PREVALENCE YOU
EXPECT TO SEE FOR GIVEN SET OF
ICD CODES AND USE ALGORITHMS
WHERE WE LOOK FOR ONE IN-PATIENT
OR TWO OUTPATIENT DIAGNOSIS
DEPENDING ON CONDITION AND WE
HAVE REGISTRY AND WE HAVE AN
ALCOHOL REGISTRY IN OUR SIFT
THEME IS GENERATIVE OF DIFFERENT
RESEARCH.
I'M NOT FAMILIAR WITH ARE
EDGETRY APPROACHES IN MENTAL
HEALTH AND WE CERTAINLY HAVE
REGISTRIES FOR OTHER CONDITIONS
AND WE HAVE A GREAT DIABETES
REGISTRY.
IT IS WELL VALIDATED AND BRINGS
TOGETHER MEDICATIONS AND LABS
AND NATURE OF MENTAL HEALTH IS
CHALLENGING AND HOW ARE YOU
GOING TO VALIDATE DIFFERENT
ALGORITHMS AND IS DIFFICULT TO
DO A COMPREHENSIVE DIAGNOSTIC
INTERVIEW WITH PATIENTS THAT IS
COMMON. WE TRY TO TAKE IT INTO
CONSIDERATION DESIGNING
ANALYSIS.
FOR EXAMPLE, YOU KNOW, IF WE ARE
INTERESTED IN, YOU KNOW, ONE
DIAGNOSIS, WE MIGHT TRY TO FOCUS
IN -- MIGHT FOCUS THE QUESTION
ON A TREATED POPULATION AND
UNDERSTANDING THAT THERE ARE ALL
THESE OTHER PEOPLE THAT ARE NOT
DIAGNOSED AND STILL COULD HAVE
THE CONDITION THAT ARE NOT BEING
OBSERVED THAT WAY.
SO -- AND THAT HAS LIMITATIONS
AND WE MAY WANT TO HAVE A REALLY
BROAD POPULATION IN OUR STUDY
AND THERE ARE SO MANY
LIMITATIONS TO USING DIAGNOSIS
AND MIGHT BE BETTER TO FOCUS IN
AND EXCLUDE PEOPLE TO TRY TO
INCREASE INTERNAL VALIDITY OF
THE ANALYSIS.
>> GREAT. REALLY GOOD POINTS.
WE DON'T HAVE MUCH TIME LEFT.
THERE IS A QUESTION FOR ALL OF
THE SPEAKERS AND PERHAPS
SOMEBODY COULD COMMENT ON THIS.
COULD YOU SAY MORE ABOUT THE
IMPORTANCE OF INVESTIGATING
WHETHER OUTCOMES OF GLP-1S ARE
BY WEIGHT LO S OR OTHER ADVERSE
EFFECTS AND IN REAL WORLD DATA
IN THOSE ANALYSIS.
>> >> YES. SO SORRY AND
REPORTED COST MEDIATED ANALYSIS
AND I WILL ADDRESS THIS
QUESTION.
SO THEORETICALLY I STILL BELIEVE
THAT LOWERING BODY WEIGHT IS
IMPORTANT CAUSAL PATHWAY THAT IS
LEADING TO THE BENEFICIAL
OUTCOMES FOR MANY CONDITIONS
INCLUDING OBESITY ASSOCIATED TO
CANCER AND METABOLIC ENDPOINTS
AND NEURODEGENERATIVE AND OUR
STUDY DIDN'T REALLY SEE MOST
INDEPENDENT EFFECT. I THINK
THERE IS SEVERAL KEY
CONSIDERATIONS AND SPECIFICALLY
FOR ADRD.
WE CONSIDER THE METABOLIC RISK
FACTORS GLUCOSE AND BMI THAT IS
MORE LIKE RISK FACTORS OF MID
LIFE THAT HAVE REALLY NOT
OPTIMAL METABOLIC PROFILE IN
THEIR AGE AND IMPACT ON LONG
TERM RISK OF ADRD RISK AND
DEMENTIA RISK AND ONE REASON AND
COHORT IS IN LATER YEARS IN LIFE
AND OVER 65 YEARS OLDER.
AND SO THEY PROBABLY PLAY
MINIMAL ROLE ON CAUSAL PATHWAYS
AND ALSO ACTUALLY IN DEBATE AND
NEW [INDISCERNIBLE] REGARDING
BMI IN OLDER POPULATION AND IN
THE OVER ALL WELLBEING AS WELL
AS THE DEMENTIA OUTCOMES
PRIORITY.
SO YEAH. THAT IS I THINK ONE
OTHER REASON THAT BODY WEIGHT IN
OLDER POPULATION I THINK YEAH.
REALLY WHETHER OLDER POPULATION
THINKS THAT THE INTENSIVE WEIGHT
LOSS IS INTENSIVE EFFECT OF
GLP-1S ARE NOT.
YEAH.
>> ONE OF THE CHALLENGES TO
BRING IT BACK TO WHERE WE
STARTED IS I THINK THAT LOTS OF
CHALLENGES ARE MECHANISTIC
PATHWAYS IS WE, ONE, DON'T FULLY
UNDERSTAND HOW GLP-1-BASED
THERAPIES WORK ACROSS ALL
SYSTEMS AND IT IS SO WELL --
THAT IS HOW WE STARTED
YESTERDAY. IT WAS AN EXCELLENT
DEMONSTRATION OF THAT AND FACT
THAT, YOU KNOW, LOTS OF THE
OUTCOMES WE WERE TALKING ABOUT
TODAY ARE ALL RELATED AND CKM
OUTCOMES BECAUSE OF UNDERLYING
METABOLIC DISFUNCTION OCCURRING
AS RESULT OF DYSFUNCTIONAL
ADIPOSE TISSUE IS NOT ABOUT HOW
DRIVING EVERYTHING.
I THINK IT IS VERY CHALLENGING
TO LOOK AT SINGULAR OUTCOMES
AND, YES. WE DO A GOOD JOB AT
ADDRESSING CONFOUNDING -- YOU
KNOW, CONFOUNDERS AND BASELINE
RISK FACTORS AT BASELINE AND CAN
DO TIME VARYING CONSIDERATIONS
DURING TREATMENT AND WHAT DO WE
DO WHEN OUTCOMES ARE AS WELL AND
THEY ARE DEPENDENT AND THEY ARE
NOT AND IS CHALLENGE THAT DRIVES
NOT IMPACTS REAL WORLD STUDIES
AND CLINICAL TRIALS AS WELL AND
SAW IN COBTS AND TARGET TRIALS
AND DIABETES AND THINK IT COMES
TO THE FACT THAT THIS DIRECT
LINES AND SOMETIMES I MEAN IT IS
AMAZING AND WE CAN TARGET
UNDERLYING PATHWAY IF WE DON'T
FULLY UNDERSTAND WHAT IT IS WITH
THAT IT COMES WITH RISK AND WE
DON'T KNOW WHAT OTHER PATHWAYS
MIGHT BE TRIGGERED AT SAME TIME
AND WHAT ARE WE MISSING AND WHAT
HAVEN'T WE LOOKED AT AND WITH
MEDICATIONS WITH PLEAOTROPIC
EFFECT WE ARE DISCOVERING HOW
YOU KNOW WHAT EFFECT VERSUS
OUTCOME OF DATA AND RUN INTO OUR
STUDIES LOOKING AT WHAT I CALL
FALSE FICTION ENDPOINT OF
PNEUMONIA FIRST PROPOSING GRANTS
AND TURNS OUT NOT FALSE FICTION
ENDPOINTS BUT OUTCOME AND WHAT
DO YOU DO WITH THAT AND KNOW
WHICH IS WHICH AND THINK GLPS
ARE UNIQUELY DIFFICULT TO STUDY
BECAUSE OF INTERDEPENDENCIES OF
UNDERLYING PATHOLOGY AND US NOT
KNOWING WHERE THEY TRULY ACT.
>> RIGHT. GREAT POINT. I LOVE
THAT YOU LINKED IT RIGHT BACK
INTO THE VERY FIRST TALK OF THE
WORKSHOP. I THINK WITH THAT WE
WILL GO AHEAD AND WRAP UP THE
SESSION.
DOES ONE OF THE ORGANIZERS WANT
TO COMMENT ON -- THANK YOU. ON
THE NEXT PLANS?
>> YEAH. JUMPING IN AND SAYING
THANK YOU, EVERYBODY.
EXCELLENT PRESENTATIONS TODAY.
THANK YOU FOR WONDERFUL
MODERATION.
IT WAS SCHAKTLY WHAT WE WERE
LOOKING FOR OUT OF THE SESSION
TODAY.
AS WE MOVE INTO LUNGE BREAK WE
WILL JUST TAKE A 25 MINUTE -- 26
MINUTE LUNCH BREAK AT THE MOMENT
AND RECONVENE AT TIME WE
PREVIOUSLY ALLOTTED TO COME BACK
AT 1:15 FOR A SUMMARY.
AS YOU MOVE INTO THE SESSION WE
WOULD LIKE TO HAVE EVERYONE PUT
INTO THE CHAT WHAT YOU WERE
TAKING AWAY AS KEY MAJOR GAPS OR
OPPORTUNITIES FOR RESEARCH IN
THE FIELD AND SIMILAR TO WHAT WE
DID AT THE OUTSET AND WANT YOU
TO REREFLECT ON EVERYTHING YOU
LEARNED AND ADD INTO THE CHAT
THOSE REFLECTIONS ON MAJOR GAPS
AND UPVOTE PEOPLES GAPS THEY PUT
IN THERE TO SAY THAT THIS IS
SOMETHING THAT I AGREE IS REALLY
IMPORTANT FOR US TO ADDRESS AS
WE MOVE FORWARD IN THE FIELD.
AND IF YOU CAN, WE HAVE -- THE
ORGANIZERS HAVE IDENTIFIED
SEVERAL KEY THEMES I'M PUTTING
IN THE CHAT NOW.
IF YOU THINK ANY MAJOR GAPS FIT
WITH VARIOUS THEMES WE ARE
FOCUSING ON YOU CAN CALL THAT
OUT AS A THEME OR ECONOMIC THEME
OR SOME OTHER THEME. IT DOESN'T
FIT INTO THE THEMES THAT IS FINE
AND PUT IT IN THE CHAT AND WE
WOULD LOVE TO HEAR ABOUT WHAT
MAJOR GAPS ARE THAT YOU THINK.
WE ARE COLLATING THEM AND WILL
TALK MORE ABOUT THEM WHEN WE COME BACK AT 1:15 AFTER LUNCH. THANK YOU.
>> WELCOME BACK, EVERYONE.
I KNOW THAT WAS A SHORT BREAK
FOR LUNCH, BUT WE ARE ATTEMPTING
TO COME BACK TOGETHER AND TO
SYNTHESIZE EVERYTHING THAT WE'VE
LEARNED AND ALL THE IDEAS THAT
HAVE BEEN GENERATED OVER THE
LAST COUPLE DAYS TO HELP US MOVE
THE FIELD FORWARD AND FIGURE OUT
WHAT ARE THE MAJOR GAPS AND
OPPORTUNITIES FOR RESEARCH
TOGETHER COLLABORATIVELY.
AND SO THE CO-CHAIRS AND I HAVE
BEEN THINKING ABOUT THIS AS
WE'VE BEEN PREPARING THIS
WORKSHOP, BUT ALSO INTEGRATING,
SYNTHESIZING ALL THE SUGGESTIONS
THAT HAVE BEEN COMING THROUGH
OVER THE LAST TWO DAYS.
SO WE WANTED -- I JUST REALIZED
MY MICROPHONE WAS MUTED.
HI, EVERYBODY.
AND WELCOME BACK TO THIS
SESSION, WHERE WE'RE GOING TO BE
SYNTHESIZING MAJOR GAPS AND
OPPORTUNITIES FOR RESEARCH IN
THIS -- IN THIS AREA TO HELP
MOVE THE NEEDLE FORWARD AND
ESTABLISH THE NEXT PHASE OF
RESEARCH AND CLOSE SOME OF THESE
GAPS IN THE COMING DECADE.
AS THE CO-CHAIRS AND I WERE
WORKING TOGETHER OVER THE PAST
YEAR BUT ALSO IN THE LAST TWO
DAYS, IN PARTICULAR WE'VE BEEN
TRYING TO SYNTHESIZE KEY THEMES
AROUND WHAT THE MOST IMPORTANT
AREAS ARE FOR US TO BE
ADDRESSING IN THE COMING DECADE,
AND SOME OF THESE THEMES ARE
LISTED HERE, AND MAYBE THERE'S
OTHER THEMES THAT WE DIDN'T
CAPTURE THAT WE WOULD LOVE TO
HEAR FROM PEOPLE IF WE'VE MISSED
ANYTHING, AND SO WE'RE GOING TO
TAKE SOME TIME TO BREAK DOWN
EACH OF THESE THEMES IN THE NEXT
45 MINUTES, UNDERSTAND WHAT
AREAS HAVE BEEN IDENTIFIED AS
MAJOR GAPS AND OPPORTUNITIES,
AND THEN COME BACK AROUND AFTER
WE'VE GONE THROUGH THESE SLIDES.
WE HAVE ONE SLIDE OR TWO FOR
EACH OF THESE DIFFERENT TOPICS.
WE'RE GOING TO COME BACK AROUND
AND TRY TO FILL IN THE GAPS AND
WE'LL BE ALSO MONITORING THE
CHAT.
IF SOMETHING COMES TO MIND AS
WE'RE GOING THROUGH THIS AREA,
ONE OF THESE AREAS ABOUT -- THIS
WOULD BE A REALLY IMPORTANT GAP,
IT DOESN'T SEEM TO BE LISTED,
PLEASE DO PUT IT RIGHT INTO THE
CHAT.
WE'LL BE TRYING TO PULL THOSE IN
AS WE'RE GOING ALONG.
SO I'M GOING TO KICK US OFF WITH
JUST A QUICK SUMMARY.
MY MICROPHONE KEEPS MUTING.
I'M GOING TO BE KICKING US OFF
WITH THE -- TAKE A LOOK AT THE
LONG-TERM OUTCOMES GAP.
SO FIRST WHAT WE HEARD PRETTY
CLEARLY IS THAT OBSERVATIONAL
TARGET TRIAL STUDY DESIGNS SEEM
TO BE PARTICULARLY SUITABLE FOR
INVESTIGATIONS OF LONG TERM
OUTCOMES, AND WE DO NEED LONG
TERM DATA ON THE METABOLIC BODY
COMPOSITION, BEHAVIORAL IMPACTS
OF COMING OFF OF THESE
MEDICATIONS, BUT ALSO THE LONG
TERM IMPACTS OF BEING ON THEM.
DO BENEFITS WANE OVER TIME AND
ARE THERE SUBSETS OF PATIENTS
THAT HAVE THE MOST BENEFIT.
ARE THERE PARTICULAR BMI RANGES
OR COMORBIDITIES, AND ARE THERE
FACTORS THAT GO INTO DETERMINING
THE HETEROGENEITY IN LONG-TERM
RESPONSE TO TREATMENT.
WHAT MORE CAN WE LEARN FROM REAL
WORLD DATA TO HELP IMPROVE
RESPONSE OR MAYBE PATIENT
SELECTION FOR PARTICULAR
MEDICATIONS.
IN PARTICULAR, MAYBE EHR
INTEGRATED TOOLS CAN HELP US
PREDICT OUTCOMES USING REAL
WORLD DATA.
AND ONE OTHER IDEA WAS TO BEGIN
TO UNDERSTAND OR UNPACK SOCIAL
DETERMINANTS OF HEALTH, AND
THEIR INFLUENCE ON LONG TERM
RESULTS IN THIS POPULATION.
AN IMPORTANT TOPIC THAT WAS
RAISED WAS EVALUATING OFF LABEL
USE OF GLP-1s AND THE FACT
THAT TARGET TRIALS MAY BE
SPECIFICALLY WELL SUITED FOR
EVALUATING OFF LABEL USE.
THERE WERE SEVERAL QUESTIONS
ABOUT THE TYPES OF THERAPY OR
THE COMBINATIONS OF THERAPY.
SO IS STEP THERAPY MORE
EFFECTIVE OR COST-EFFECTIVE THAN
STRAIGHT TO GLP-1 THERAPY FOR
ANTIOBESITY MEDICATION CARE OR
FOR OTHER DISEASES?
IS IT BENEFICIAL TO COMBINE
DIFFERENT MEDICATIONS TOGETHER
TO ACHIEVE GREATER OUTCOMES?
ARE THE NEWER MEDICATIONS MORE
EFFECTIVE OR SAFER THAN
METABOLIC SURGERY FOR TREATING
PATIENTS WITH SEVERE OBESITY?
SO A NUMBER OF COMPARATIVE
EFFECTIVENESS QUESTIONS THAT
MAYBE REAL WORLD DATA CAN SHARE
SOME LIGHT ON.
THEN A QUESTION ABOUT THIS
LEGACY EFFECT IDEA FOR DIABETES,
WHICH IS AFTER A DEFINED PERIOD
OF TREATMENT WITH A GLP-1, EVEN
AFTER YOU STOP TAKING IT, MAYBE
THERE'S A LEGACY EFFECT OF
CONTINUED IMPROVEMENTS IN HEALTH
LIKE HAS BEEN DESCRIBED IN
PATIENTS WITH GLUCOSE LOWERING
AGENTS IN TYPE 2 DIABETES.
SO EVEN WHERE THERE IS WEIGHT
REGAIN OR WORSENING OF
COMORBIDITIES, IS THERE STILL
SOME PERSISTENT BENEFICIAL
EFFECT OF HAVING HAD A PERIOD OF
TIME ON THESE MEDICATIONS?
ADDITIONAL LONG TERM QUESTIONS
EMERGE SORT OF OUT OF OUR
CONVERSATIONS ABOUT SPECIFIC
DISEASES AND I POINT AGAIN TO
THIS FIGURE BY DANIEL DRUCKER
ESTABLISHED INDICATIONS FOR
OBESITY BEING ON THIS LEFT-HAND
SIDE, AND THERE WERE A LOT OF
ESTABLISHED INDICATIONS THAT
WERE COVERED IN OUR TALKS, AND
IMPORTANT TO THINK ABOUT FOR
REAL WORLD DATA ANALYSES THAT
MANY OF THOSE ESTABLISHED
INDICATIONS ARE COVERED BETTER
THAN OBESITY, SO DIABETES,
CARDIOVASCULAR DISEASE, SLEEP
APNEA MAY BE COVERED, AND SO THE
PATIENTS MAY HAVE BETTER ACCESS
AND ADHERENCE TO MEDICATIONS IN
THOSE PARTICULAR SUBGROUPS, AND,
THEREFORE, MIGHT BE ABLE TO
EVALUATE LONG-TERM EFFECTS
BETTER.
AND BUT THERE'S ALSO SPECIFIC
QUESTIONS THAT WERE ARISING WITH
SOME OF OUR SPEAKERS AROUND
DIFFERENT ESTABLISHED
INDICATIONS, ONE THAT CAME TO
MIND WAS HOW DO GLP-1s IMPACT
OTHER TREATMENTS FOR THOSE
DISEASES OR HOW IS THE
BENEFIT -- COST-BENEFIT RATIO OF
HAVING MULTIPLE TREATMENTS LIKE
THAT.
FOR EXAMPLE, WHAT WAS THE ADDED
VALUE OF GLP-1 ADDED TO
SGL-2 ADDED TO PATIENTS WITH
DIABETES, SO THINKING ABOUT
COMBINATION THERAPIES OF
ESTABLISHED TREATMENTS AND
GLP-1s IN THESE VARIOUS
INDICATIONS.
AND AS WE HEARD IN THE LAST
SESSION, OUR DISE ARE DISEASE OS
MEDIATE BID WEIGHT LOSS OR A1C
IMPROVEMENT OR ARE THERE OTHER
DIRECT GLP-1 ACTIONS AS AT THE
TOP OF THIS FIGURE THAT MAY BE
HAVING THE EFFECT ON THOSE OUTCOMES.
THEREWERE SEVERAL QUESTIONS ABOUT TYPES OF THERAPY OR
COMBINATION OF THERAPY IS IT
COST EFFECTIVE THAN STRAIGHT GL1
THERAPY FOR ANTI-OBESITY
MEDICATION CARE OR OTHER
DISEASES AND IS IT BENEFICIAL TO
COMBINE DIFFERENT MEDICATIONS
TOGETHER TO ACHIEVE GREATER
OUTCOMES AND ARE THERE NEWER
MEDICATIONS MORE EFFECTIVE OR
SAFER THAN METABOLIC SURGERY FOR
TREATING PATIENTS WITH SEVERE
OBESITY AND NUMBER OF DIFFERENT
COMPARATIVE EFFECTIVENESS
RELATED QUESTIONS WITH VARIABLE
DATA CAN SHED LIGHT ON AND
QUESTION ABOUT LEGACY EFFECT
IDEA OF DIABETES THAT AFTER
DEFINED THERAPY TREATMENT AFTER
YOU STOP TAKING IT LEGACY EFFECT
OF CONTINUED IMPROVEMENTS HEALTH
THAT IS DESCRIBED IN PATIENTS
WITH GLUCOSE LOWERING IN TYPE 2
DIABETES AND WHERE THERE IS
WEIGHT GAIN FOR WORSENING OF
COMORBIDITIES IS THERE
PERSISTENT BENEFICIAL EFFECT OF
HAVING HAD A PERIOD OF TIME ON
MEDICATIONS?
ADDITIONAL LONG-TERM QUESTIONS
EMERGE SORT OF OUT OF OUR
CONVERSATIONS ABOUT SPECIFIC
DISEASES POINTING AGAIN TO
FIGURE BY DANIEL ESTABLISHING
INDICATIONS OF OBESITY BEING ON
LEFT-HAND SIDE AND ESTABLISHED
INDICATIONS THAT WERE COVERED IN
OUR TALKS AND IMPORTANT TO THINK
ABOUT FOR REAL WORLD DATA
ANALYSIS THAT MANY ESTABLISHED
INDICATIONS ARE COVERED BETTER
THAN OBESITY AND SO DIABETES AND
CARDIOVASCULAR DISEASE AND SLEEP
APNEA MAY BE COVERED AND
PATIENTS MIGHT HAVE BETTER
ACCESS AND TO MEDICATIONS IN
PARTICULAR SUBGROUPS AND
THEREFORE MIGHT BE ABLE TO
EVALUATE LONG-TERM EFFECTS
BETTER AND THERE IS ALSO
SPECIFIC QUESTIONS THAT WERE
ARISING WITH SOME SPEAKERS
AROUND DIFFERENT ESTABLISHED
INDICATIONS AND ONE THAT CAME TO
MIND IS HOW DO GLP-1 IMPACT
OTHER TREATMENTS FOR DISEASES
AND WHAT -- YOU KNOW, HOW IS THE
BENEFIT COST BENEFIT RATIO
HAVING MULTIPLE TREATMENTS LIKE
THAT AND FOR EXAMPLE WHAT IS
ADDED VALUE OF GLP-1 ADDED TO
SGLT2 IN PATIENTS WITH TYPE 2
DIABETES AND THINKING IN
COMBINATION THERAPIES IN
ESTABLISHED TREATMENTS IN GLP-1S
IN VARIOUS INDICATIONS AND AS WE
HEARD IN THE LAST SESSION, ARE
DISEASE OUTCOMES MEDIATED BY
WEIGHT LOSS FOR A1C IMPROVEMENT
AND ARE THERE OTHER DIRECT GLP-1
ACTIONS AT TOP OF FIGURE THAT
MAY BE HAVING EFFECT ON
OUTCOMES?
SHIFTING TO INVESTIGATIONAL
OUTCOME SIDE OF THINGS, WE HEARD
ABOUT QUITE A FEW OF THESE TODAY
AND NOT ALL OF THEM. ADDITIONAL
AREAS ARE NOT LISTED ON THE
SLIDE TALKING ABOUT TODAY
DEPRESSION AND SUICIDALITY AND
EATING DISORDERS AND CANCER AND
LOTS OF POTENTIAL OUTCOMES THAT
COULD BE ADDRESSED HERE.
WHERE WOULD BE USING -- USING
REAL-WORLD DATA TO LOOK AT
LONG-TERM OUTCOMES AND THERE ARE
CONCERNS THERE FOR A LOT OF
THESE CONDITIONS BOTH ON
ESTABLISHED AND ON
INVESTIGATIONAL SIDE AND HOW WE
ACCURATELY IDENTIFY THESE AND
SOME QUESTIONS WERE WRESTLED
WITH IN SPEAKERS TODAY AND HOW
DO WE USE ICD CODES AND EHR OR
LAB DATA AND IS NATURAL LANGUAGE
PROCESSING OR OTHER LINKAGES TO
EVALUATE OUTCOMES ARE REALLY
IMPORTANT CONSIDERATIONS.
SO THE NEXT AREA OF OUR KEY
THEME THAT EMERGED IS CLEARLY
AROUND ECONOMICS AND COVERAGE
AND SO MANY QUESTIONS AROUND
THIS. ARE THERE SIGNIFICANT
COST OFFSETS AND SAVINGS FROM
GLP-1 USES AND IN OTHER WORDS DO
CHRONIC CONDITIONS IMPROVE
SIGNIFICANTLY SO OTHER HEALTH
OUTCOMES BECOME MUCH LESS
EXPENSIVE AS RESULT OF USING
GLP-1S AND EXPENSIVE THEMSELVES
AND SHOULD OLDER LESS EXPENSIVE
MEDICATIONS BE CONSIDERED IN
CERTAIN PATIENT GROUPS AND IF SO
WHICH CRITERIA DID WE USE TO
GUIDE THIS SELECTION AND HOW DO
WE RECONCILE UPFRONT COST OF
GLP-1S WITH LONG TERM COST
SAVINGS AND IDEA THAT COMMERCIAL
PAYERS ARE TAKING THE BRUNT
PERHAPS CMS AND MEDICARE WOULD
REALIZE COST BENEFITS AND
UNDERSTANDING HOW THOSE EARLY
COST OF GLP-1S MIGHT TRANSLATE
INTO BENEFITS FOR CNS AND WHAT
PRICE OF GLP-1S WOULD BE NEEDED
IN ORDER TO SAVE MONEY ON HEALTH
CARE COSTS?
IS THERE A THRESHOLD OF WHICH
GLP-1 TREATMENT IS ACTUALLY COST
SAVING? DO DIFFERENT LEVELS OF
COST SHARING AND OUT OF POCKET
COPAYMENTS AND FILL HAVE
SIGNIFICANT IMPACT ON ADHERENCE
AND WEIGHT LOSS OUTCOMES AND
DIFFERENT SYSTEM LEVEL AND
NATURAL EXPERIMENTS THAT CAN BE
DONE TO EVALUATE THESE -- THERE
IS POLICY CHANGES AND
IMPLEMENTATION APPROACHES TO
USING GLP-1S TO SEE IF THEY
REDUCE GAPS IN HEALTH CARE
QUALITY OR HEALTH OUTCOMES AND
THERE IS A POINT TO
MICROSIMULATION RESEARCH AND
10-YEAR FOLLOW-UP WINDOW
EVALUATING SUBPOPULATIONS AND
DISABILITY AND EMPLOYMENT
OUTCOMES TO HELP UNDERSTAND THE
SOCIETAL IMPACT OF USE OF THESE
MEDICATIONS AND THERE WAS A
QUESTION ABOUT COMPREHENSIVE
LIFESTYLE PROGRAM COSTS AND IS
THERE A NET COST BENEFIT OF
COMBINING THESE THINGS TOGETHER?
CAN WE DEMONSTRATE A COST
BENEFIT OF COMBINING THEM
INSTEAD OF USING AOMS WITH VERY
LIGHT TOUCH OF LIFESTYLE
SUPPORT.
THEN I WOULD RECALL FROM
COLLEAGUES AT PRINT
CONGRESSIONAL BUDGET OFFICE TO
SAY CAN YOU COMPARE A -- THESE
MEDICATIONS AGAINST PEOPLE WHO
DON'T TAKE THEM?
EVEN THOUGH THERE IS CHALLENGES
THERE WE HAVE HEARD ABOUT
CHALLENGES TODAY FROM KRISTINA
AROUND COMPARING AGAINST
UNTREATED GROUPS AND HOW TO BEST
DO THAT INFORMING PAYERS AROUND
VARIOUS COMPLEX ISSUES AND WILL
TURN IT TO LESLEY WHO WILL TALK
A BIT ABOUT OTHER TOPICS OR KEY
THEMES.
>> GREAT. THANK YOU, DAVID.
SO ESPECIALLY YESTERDAY, WE
HEARD.
>> YOU ARE MUTED ON MY END,
LESLEY.
>> LET'S SEE. I'M UNMUTED HERE.
CAN YOU HEAR ME NOW?
>> I CAN HEAR YOU.
>> YES.
>> I CAN HEAR YOU.
>> OKAY. GREAT. THANK YOU. SO
YESTERDAY IN PARTICULAR, WE
HEARD SEVERAL QUESTIONS RELATED
TO OR MAJOR GAPS RELATED TO
MAINTENANCE ADHERENCE AND DOSING
AND EARLIER QUESTION THAT CAME
UP WAS WHAT ARE BEST PRACTICES
FOR TAPERING OFF OF GLP-1S IN
COMBINATION POTENTIALLY WITH
LIFESTYLE INTERVENTIONS SO WE
REDUCE INCIDENCE OF WEIGHT
REGAIN.
KIND OF RELATED TO THAT AND
NEEDING TO UNDERSTAND
OFF-RAMPING OR DEPRESCRIBING
REGIMENTS AND WHAT MAINTENANCE
DOSE REGIMENTS MIGHT LOOK LIKE
AFTER DESIRED WEIGHT LOSS HAS
BEEN ACHIEVED.
RELATED TO I THINK AN ISSUE OR
GAP THAT DAVID IDENTIFIED IS A
NEED TO IDENTIFY WHICH PATIENTS
WILL DO BEST WITH GLP ONES
INDEFINITELY VERSUS THOSE WHO
WILL BE ABLE TO SUCCESSFULLY
TAPER OR SWITCH TO SOME KIND OF
MAINTENANCE THERAPY.
AND THE ISSUE OF MICRODOSING
ALSO CAME UP AND NEED FOR
EVIDENCE-BASED RECOMMENDATIONS
FOR MICRODOSING.
THE OTHER ISSUE WE HEARD WAS
JUST ABOUT THE BARRIERS FOR
PATIENTS RECEIVING AND
CONTINUING GLP-1 PRESCRIPTIONS
IN THE LONG TERM AND TO THE
EXTENT TO WHICH SIDE-EFFECTS
LEAD TO DISCONTINUATION RATES
VERSUS ECONOMIC OR COVERAGE
ISSUES.
AND THEN ON THE NEXT SLIDE, WE
-- NOT SURE WHO IS ADVANCING.
MAYBE DAVID?
WE ALSO IDENTIFIED SEVERAL
QUESTIONS. DAVID, ARE YOU ABLE
TO ADVANCE THE SLIDES?
NOT SURE THAT I AM.
I WILL TALK FROM MY
RECOLLECTION. THERE WE GO.
BACK ONE MAYBE TO THE PRAGMATIC
TRIALS.
THERE WE GO. GREAT.
THANK YOU.
WE -- AFTER THE PRAGMATIC TRIALS
DISCUSSION, WE IDENTIFIED
SEVERAL QUESTIONS THAT MIGHT BE
PARTICULARLY JER MAIN FOR
PRAGMATIC TRIALS AND CERTAINLY
HEAD TO HEAD COMPARISONS OF
ALTERNATE AND ANTI-OBESITY
MEDICINES ESPECIALLY IN DIVERSE
HEALTHCARE SETTINGS.
WE ALSO TALKED ABOUT PRAGMATIC
TRIALS BEING THE APPROPRIATE WAY
TO REALLY TEST STRATEGIES FOR
TAPERING MEDICATIONS IN
COMBINATION WITH LIFESTYLE
INTERVENTIONS.
THE COMPARATIVE EFFECTIVENESS
ISSUE IN GENERAL WAS RAISED
INCLUDING NOT JUST GLP-1S BUT
OTHER ALTERNATIVES FOR WEIGHT
LOSS.
AND THEN THE QUESTION OF WHETHER
STEPPED CARE THERAPY IS MORE
EFFECTIVE AND LESS EXPENSIVE
THAN GOING STRAIGHT TO
TREZEPIDIDEO TRANCE GLUM ATIED
AND THERE IS SWITCHING AND
SUGGESTED THAT PRAGMATIC TRIAL
MIGHT BE THE BEST WAY FOR US TO
LOOK AT THAT -- THAT SORT OF --
THOSE SWITCHING OPTIONS WHEN
PATIENTS FAIL ONE MEDICATION.
IN RELATED TO AN ISSUE THAT
DAVID BROUGHT UP IN HIS SLIDES.
AGAIN, WHAT -- HOW INTENSIVE
DOES THE THERAPY NEED TO BE?
LIFESTYLE INTERVENTION NEED TO
BE TO SUPPORT GLP-1S FOR WEIGHT
LOSS AND ACTUALLY DOING THAT --
DOING THOSE COMPARISONS AND
MAYBE EVEN USING AN AT-BASED
APPROACH VERSUS INTENSIVE GROUP
OR INDIVIDUAL COUNSELING
APPROACH TO LIFESTYLE
INTERVENTIONS.
WE ALSO TALKED ABOUT IMPORTANT
QUESTIONS RELATED TO OFF-RAMPS
FOR MEDICATIONS.
AGAIN, DO WE -- WE IS THERE A
POTENTIAL FOR INTERMITTENT GL1
THERAPY OR SWITCHING TO ORAL
ANTI-OBESITY MEDICATIONS OR
INTENSIVE LIFESTYLE INTERVENTION
THAT MIGHT BE REALLY WELL-SUITED
FOR A PRAGMATIC TRIAL.
ALSO, USING A TRIAL TO COMPARE
DIFFERENT TITRATION SCHEDULES TO
LOOK AT THE EFFECT OF THOSE
TITRATION SCHEDULES ON OUTCOMES
LIKE ADHERENCE, WEIGHT LOSS, AND
CLINICAL OUTCOMES.
DARREN, MAYBE TO YOU FOR THE
NEXT ONES.
>> THANK YOU, LESLEY.
SO WE ALSO SPOKE A LOT ABOUT
SUBGROUPS AND ONE OF THEM WAS
THAT OBESITY WAS NOT A
HOMOGENEOUS CONDITION AND IT
WILL BE GOOD TO STUDY EFFECTS OF
GLP-1-BASED THERAPIES WITHIN
THIS LARGE GROUP THAT WE
COLLECTIVELY CALL OBESITY.
SPENDING A LOT OF TIME FOCUSING
ON PEDIATRIC POPULATION AND
THERE IS A NUMBER OF QUESTIONS
THAT WERE RAISED.
ONE WAS ABOUT ACCESS OF THE
MEDICATION AND BY -- BY
PEDIATRIC POPULATION AND YOUNG
ADULT WITH COMORBID CONDITIONS.
WE ALSO TALKED ABOUT BENEFIT AND
HARMS OF THIS PARTICULAR
POPULATION AND THERE WAS AN
EXCELLENT COMMENT FROM A
PARTICIPANT ABOUT TAKING MORE OF
A LIFE COURSE LENS TO THIS
POPULATION FOLLOWING PEDIATRIC
POPULATION INTO ADULTHOOD AND SO
ON.
SO THAT WAS SOMETHING THAT STUCK
WITH ME.
THERE WAS SOME DISCUSSION ABOUT
PREGNANT INDIVIDUALS AND BENEFIT
AND RISK OF THIS MEDICATION ON
THE MOMS AND THE BABY.
SO THAT WAS SOMETHING THAT WE
DISCUSSED TODAY.
WE KNOW THAT PREGNANT
INDIVIDUALS WERE USUALLY
EXCLUDED FROM CLINICAL TRIALS.
REAL WORLD DATA STUDIES ARE
STILL THE PRIMARY SOURCE FOR
SAFETY AND EFFECTIVENESS
INFORMATION FOR PREGNANT
INDIVIDUALS.
NEXT SLIDE, PLEASE.
SO IN ADDITION TO THE BENEFITS
OF GLP-1S BASED THERAPY WE SPOKE
ABOUT POTENTIAL HARMS AND THE
SESSIONS EARLIER THIS MORNING
FOCUS ON THE NUMBER OF
CONDITIONS AND SOME OF THEM WERE
ABOUT POTENTIAL ADVERSE EFFECTS
OF GLP-1 BASED THERAPY AND
TALKING ABOUT SUICIDALITY AND
MENTAL HEALTH CONDITIONS AND
CERTAIN EATING DISORDERS.
CERTAIN CANCERS.
AND SOCIETAL DEVELOPMENT IN
IMMEDIATAT TRICK POPULATION AND
AS MENTIONED THERE IS QUITE A
BIT OF STUDIES ON SUICIDAL
THOUGHTS ON GLP-1 THERAPY AND
FINISHING STUDY AND HOPEFULLY WE
WILL SEE RESULTS SOON.
NEXT SLIDE, PLEASE.
SO THERE WAS A -- QUITE A BIT OF
DISCUSSION OF LIFESTYLE
INTERVENTIONS ON SEVERAL FRONTS.
ONE IS ONE BEST PRACTICE FOR
BEHAVIORAL LIFESTYLE INNOVATION
THAT COULD ACCOMPANY USE OF
GLP-1-BASED THERAPIES AND
COMMENT ABOUT WHETHER WE SHOULD
FOLLOW WHAT WE ARE DOING FOR
BARIATRIC SURGERY AND FOLLOWING
THE SAME PROCESS FOR GLP-1-BASED
THERAPY.
ANOTHER QUESTION IS HOW MUCH OF
THIS INTERVENTION IS NEEDED?
TALKING MORE ABOUT THIS COST AND
SOCIETAL IMPACT OF THIS
CO-INTERVENTION AND DR. LEWIS
EARLIER TODAY SPOKE ABOUT
METHODOLOGICAL ISSUES WHEN DOING
REAL WORLD STUDIES ON GLP-1S AND
HOW TO THINK ABOUT THESE
BEHAVIORAL INTERVENTION EITHER
BEING CONFOUNDERS OR
INTERMEDIATE VARIABLES FOR
THINGS WE WANT TO LOOK AT AND
ARE METHOD LOGICAL ISSUES
ASSOCIATED WITH LIFESTYLE
INTERVENTION AS WELL.
NEXT SLIDE, PLEASE.
CAN YOU GO UP ONE SLIDE? FOR
THE -- SO METHODOLOGICAL ISSUES
-- THIS IS AN INTERESTING TOPIC.
WE SPOKE A LOT ABOUT BIASES THAT
COULD ARISE FROM REAL WORLD DATA
STUDIES AND DR. HERNON SPOKE
ABOUT [INDISCERNIBLE] BIAS AND
THINGS THAT ARE SPECIFIC TO REAL
WORLD DATAS AND SOME
METHODOLOGICAL ISSUES SPECIFIC
TO GLP-1-BASED THERAPIES THAT
ARE MOSTLY ABOUT PEDIATRIC
EFFECT OF DRUGS AND DRUGS WORK
ON SO MANY SYSTEMS IN THE BODY
AND WORK ON SO MANY OUTCOMES WE
ARE INTERESTED IN AND THERE WAS
SOME DISCUSSION ABOUT MANY OF
THE OUTCOMES BEING
INTERCONNECTED AND IT IS HARD TO
STUDY GIVEN OUTCOME IN
ISOLATION.
WHEN WE TRY TO GET DEEPER INTO
THE SPECIFIC MECHANISM FOR HOW
GLP-1S INFLUENCE CERTAIN
OUTCOME, THIS GETS INTO WHETHER
WE NEED TO DO SOME SORT OF
MEDIATION ANALYSIS.
THE QUESTION IS WE ARE STILL
TRYING TO FIGURE OUT HOW THESE
DRUGS WORK IN OUR BODY.
SO WHETHER IT IS PREMATURE OR
WHETHER WE HAVE DATA TO MAKE
SURE THAT T-CELL SPECIFIC
MECHANISM, I THINK THERE WAS --
THERE IS INTERESTING
METHODOLOGICAL ISSUES THAT COULD
BE EXPLORED THERE.
NEXT SLIDE, PLEASE.
MAYBE GO UP ONE SLIDE TO THE
DATA ENGAGED DISCUSSION.
SO ONE THEME THAT EMERGED DURING
DISCUSSION EARLIER TODAY IS THE
NEED FOR DATA LINKAGES.
WE STARTED TO TALK ABOUT THE
STRENGTHS AND WILL IMITATIONS OF
SPECIFIC TYPES OF REAL WORLD
DATA SOURCES THAT ARE GOOD FOR
CERTAIN THINGS AND LACK OTHER
INFORMATION THAT WE NEED TO
STUDY GLP-1-BASED THERAPIES AND
ONE IDEA IS TRYING TO LINK
DIFFERENT COMPLEMENTARY DATA
SOURCES TO GET A MORE
COMPREHENSIVE PICTURE OF
PATIENTS AND WHAT HAPPENS TO
WHEN THEY TAKE MEDICATIONS.
SO LINKING BETWEEN CLAIMS DATA
AND EHR OR LINKING BETWEEN
OEC EHR
REGISTRY AND CLAIMS THAT EMERGE
AS A COMMON THEME EARLIER TODAY
AND ALSO WAS DISCUSSION ABOUT
CONTINUED FOLLOW UP OF
INDIVIDUALS PARTICIPATING IN
PRAGMATIC TRIAL FOR EXAMPLE AND
SOME SPEAKERS SHOW REAL-WORLD
EXAMPLE TO SHOW IT IS FEASIBLE
EVEN THOUGH TRIAL ENDED AND IT
IS POSSIBLE TO LINK TRIAL DATA
WITH OTHER REAL WORLD DATA
SOURCES TO FOLLOW PATIENTS FOR
LONG TERM OUTCOMES AND ARE ALSO
DISCUSSIONS ABOUT SOME OF THE
EMERGING MULTI-SITE OR
MULTI-NATION STUDIES TO ALLOW US
TO LOOK FOR RARE OUTCOMES AND
EXAMPLES THAT SPEAKERS PROVIDED.
I THINK THAT THOSE ARE THE
THEMES THAT WE IDENTIFIED.
MAYBE NOW IS A TIME TO GO BACK
TO INDIVIDUAL SLIDES TO SEE
WHETHER WE MISSED ANYTHING.
I SAW DAVID COMING BACK ONLINE.
>> GREAT. THANK YOU FOR THAT,
DARREN. CAN YOU HEAR ME OKAY?
>> YUP.
>> GREAT. I HAD TECH ISSUES ON
MY SIDE AND HAD TO REJOIN AND
GLAD YOU COULD HEAR ME BEFORE
ANYBODY ELSE AND CRAIG IF YOU
WOULDN'T MIND TAKING US BACK TO
LONG-TERM OUTCOME SLIDE ON WHICH
-- THERE WE GO.
I THINK WHAT WE WOULD LOVE TO
HEAR IS ARE THERE ANY ADDITIONAL
POINTS WE MISSED AS WE GO
FORWARD?
YOU KNOW, I -- I THINK THAT, YOU
KNOW, WE COVER A BIT OF GROUND
HERE IN LONG-TERM OUTCOME SLIDE
AND NEXT ONE AND THINK THAT
THERE MAY NOT BE ADDITIONAL
POINTS THAT NEED TO BE ADDED.
IF ANYBODY HAS IDEAS THAT CAME
TO MIND, YOU KNOW, I WOULD LOVE
TO HEAR FROM PEOPLE IN THE CHAT
ABOUT OTHER LONG-TERM OUTCOMES
WE NEED TO ASSESS OR ANY
CHALLENGES OR ISSUES THAT YOU
ANTICIPATE BEING AN IMPORTANT
THING TO ADDRESS IN THIS SPACE.
ANY COMMENTS COMING IN?
DARREN, I KNOW THIS IS OUR BEST
THINKING COMING TOGETHER THERE.
WE COULD MAYBE MOVE ON TO THE
ECONOMIC PIECE THAT WAS ROBUSTLY
TALKED ABOUT IN COMING TWO DAYS
AND ENDORSEMENT AND ECONOMIC
PIECE OF THIS AND OBVIOUSLY
THERE IS BIG GAPS TO FILL HERE
WE I THINK ARE HEARING FROM A
LOT OF DIFFERENT PEOPLE IN THIS
SLIDE AS WELL IN TERMS OF WHAT
DIFFERENT GAPS MIGHT BE AND HAD
A ROBUST DISCUSSION ABOUT IT
YESTERDAY AND DOES ANYBODY HAVE
ECONOMIC RELATED ADDITIONAL GAPS
THEY WOULD LIKE TO ADD TO THE
LIST?
YOU NEED IT COMING IN THERE AS
WELL SHOULD WE MOVE INTO
ADHERENCE AND MAINTENANCE DOSING
OR RELATED QUESTIONS AND HEARD
FROM LESLEY ABOUT THOSE.
ANY OTHER ISSUES AROUND
ADHERENCE OR MAINTENANCE THAT
PEOPLE ARE CONCERNED ABOUT?
THERE IS A COMMENT FROM
ORGANIZERS ABOUT VALUE-BASED
ADHERENCE DESIGN PRINCIPLES.
GREAT ONE AROUND ECONOMIC PIECE.
YEAH. NEW INNOVATIVE DESIGNS
AROUND HOW WE MIGHT PAY FOR AND
IMPROVE GOOD QUALITY FOR USE OF
GLP-1S. THAT IS GREAT WE CAN
CONTINUE THAT SUGGESTION.
OTHER QUESTIONS OR CONCERNS
ABOUT MAINTENANCE, ADHERENCE OR
DOSING OF MEDICATIONS?
I WILL ADD I THINK IT CAME UP IN
OUR SESSION TODAY AND IS JUST
OCCURRING TO ME NOW THAT I DON'T
THINK -- I DON'T THINK WE
ADEQUATELY TOUCHED ON THE DOSE
OF GLP-1 RELATED ISSUES IN OUR
DATA.
THIS IDEA THAT, YOU KNOW, WE HAD
BEEN TALKING ABOUT IDENTIFYING
WHO IS TAKING VARIOUS DRUGS AND
WHICH DOSE ARE THEY ON AND OVER
WHAT PERIOD OF TIME?
THAT TIME VARYING PIECE ON WHAT
HAPPENS TO YOUR OUTCOMES AS YOU
GET TO DIFFERENT DOSES AND
WHETHER THERE IS CLEAR DOSE
RESPONSE AS YOU SEE IN CLINICAL
TRIALS. YOU KNOW, NOT JUST
THINKING ABOUT SOMEONE ON SEM
AGO LEWDIDE OR NOT AND WHAT DOSE
ARE THEY ON ON THAT MEDICATION
AND THAT DERIVING SOME
HETEROGENEITY AND RESPONSE WE
MIGHT SEE. YOU KNOW, THAT MIGHT
BE DRIVEN BY TOLLRABILITY OR
MAYBE IT IS DRIVEN BY COST OR
MAYBE JUST ORDER EXECUTION OF
IMPLEMENTATION ON THE CARE
DELIVERY SIDE AND IN TERMS OF
TITRATION IN TERMS OF OPTIMAL
THERAPY AS WE SEE IN MANY MANY
HEALTH CONDITIONS AND WHAT ARE
VARIOUS FACTORS THAT ARE DRIVING
DOSING OVER TIME? WHAT IMPACT
DOES IT HAVE ON HEALTH OUTCOMES
THAT IS SOMETHING THAT IS COMING
TO MIND?
>> DAVID, ANOTHER POINT THAT
CAME TO MIND AS I'M REMEMBERING
IS COMMENT ABOUT USING THE TERM
ADHERENCE AS WE TYPICALLY USE IT
GIVEN THAT IN THIS -- WITH
DRUGS, GIVEN COST AND CHALLENGES
RELATED TO ACCESS, FRAMING OF
ADHERENCE MIGHT PUT MORE I WOULD
SAY MAY ATTRIBUTE MORE TO THE
PATIENT THAN IS TRULY IN THEIR
CONTROL.
IT IS NOT REALLY A GAP AS MUCH
AS IT IS NOTING THAT THE WORDS
THAT WE USE WE MAY WANT TO BE
CAREFUL ABOUT HOW WE -- WE MIGHT
WANT TO CAREFULLY DEFINE THEM.
MAKE SENSE?
>> IT DOES. THANK YOU FOR THAT
CLARIFICATION.
THERE IS ALSO A POINT IN THE
CHAT THAT IS I THINK RELATED TO
THE COST THINKING ABOUT HOW
COSTS INFLUENCE THE CHOICE OF
THE COMPARATOR.
AND THE -- THE POTENTIAL KIND OF
SELECTION ISSUES BIAS ISSUES
THAT MIGHT OCCUR DUE TO COST
DIFFERENCES.
>> GREAT ONE.
>> ALONG LINES OF ADHERENCE AND
DISCUSSION, ONE THING WE DID NOT
GET A CHANCE TO DISCUSS BUT
SOMEONE BROUGHT IT UP IS A
QUESTION WAS IMPACT OF
COMPOUNDED PRODUCTS.
BECAUSE IT IS POSSIBLE THAT SOME
PATIENTS MIGHT SWITCH TO
COMBINED PRODUCTS AND IN THE
REAL DATA SOURCES THAT WE HAVE
ACCESS TO, WE MIGHT JUST SEE
THEM AS STOPPING THE TREATMENT.
BUT THAT MIGHT NOT BE THE CASE
BECAUSE THEY MIGHT JUST BE
GETTING THE DRUG FROM OTHER
PLACES AND ARE METHODOLOGICAL
ISSUES WITH THAT.
>>.
AGREE WITH YOU, DARREN.
HOPEFULLY IN MAY OF THIS MONTH
IT IS SUPPOSED TO BE END OF
COMPOUNDING AROUND GLP-1S AND
WILL BE INTERESTING TO SEE HOW
IT PLAYS OUT THIS IS A REAL
IMPORTANT POTENTIAL GAP WITHIN
REAL WORLD DATA TO UNDERSTAND
WHAT INFLUENCE THIS MIGHT BE AND
PEOPLE COULD INVESTIGATE HOW
COMMON IT IS PEOPLE ARE GOING
AND GETTING A COMPOUND DRUG TO
ANNOUNCE PHARMACY AND
INTERESTING TIMES TO ACCESS
MEDICATIONS AND WONDER HOW MUCH
DISCONTINUATION IS OBSERVED IN
DATABASES MIGHT BE FALSE THAT --
>> IN ADDITION TO DIETARY
CONCERNS THERE IS COMMENT ABOUT
ENGAGEMENT WITH PHYSICAL
ACTIVITY OVER TIME OFTEN BEING
POORLY MEASURED HELPING CAPTURE
THAT AND IDEA TO CAPTURE REAL
TIME DATA ON LIFESTYLE FACTORS
THAT COULD INFLUENCE OUTCOMES
WITH PATIENTS GETTING GLP-1S IS
A GREAT POINT.
THANK YOU.
ANY OTHER COMMENTS ABOUT
MAINTENANCE ADHERENCE DOSING AND
PRAGMATIC TRIALS AND ANYBODY
ELSE HAVE IDEAS FOR PRAGMATIC
TRIALS AND IDEAS HOW THEY COULD
BE BEST USED TO MOVE THE FIELD
FORWARD DISTINCTLY FROM TARGET
TRIALS?
WE CAN MOVE ON TO PEDIATRIC
TOPICS THAT MIGHT BE NEXT.
I DON'T KNOW IF THERE IS ANY
OTHER FEEDBACK THAT PEOPLE HAD
AROUND VARIOUS TOPICS AND THERE
IS A LOT TO COVER IN THAT SPACE
AND ARE SUCH GOOD GAPS AND
OBVIOUSLY REAL WORLD DATA MIGHT
BE AN IMPORTANT COMPONENT OF
THAT. BACK ON PRAGMATIC TRIAL
PIECE COMMENT ABOUT STEP THERAPY
BEING A HIGH PRIORITY TO
CONSIDER FACTORIAL DESIGNS I
WILL ENDORSE THAT KAISER
PERMANENTE'S FIRMLY ADOPTING A
STEP THERAPY APPROACH IN AREA OF
OBESITY WE HAVE ALWAYS HAD THAT
IN PLACE OF IN CASE OF DIABETES
AND QUESTION REALLY BECOMES HOW
DOES A GLP-1 ON TOP OF OTHER
TREATMENTS THAT HAVE ALREADY
BEEN TRIED COMPARED TO OTHER
APPROACHES YOU KNOW SHOULD WE BE
JUMPING STRAIGHT TO GLP-1S AND
DIABETES GUIDELINES SHIFTING IN
THAT WAY AND IS INTERESTING TO
THINK ABOUT THAT IN OBESITY
SPA
SPACE.
NOT SEEING PEDIATRIC SPECIFIC
TOPICS COMING IN AND POSSIBLE
HARMS IS NEXT. SO WE HEARD
ABOUT MENTAL HEALTH AND SUICIDE
RELATED HARMS AND OTHER
POPULATIONS.
I THINK THIS IS -- YOU KNOW,
WEIGHT GAIN WAS ANOTHER TOPIC
THAT IS, YOU KNOW, COULD BE PUT
IN HARMS SECTION AND THINK WHAT
HAPPENS WHEN PATIENTS
DISCONTINUE MEDICATION IS A
REALLY IMPORTANT POTENTIAL HARM
THAT WE, YOU KNOW, NEED TO BE
CONSIDERING.
NOT ALL PATIENTS WILL TOLERATE
GLP-1S AND MAY TAKE THEM FOR A
PERIOD OF TIME AND IF THEY
TOLERATE WHERE THEY WANT TO STAY
ON THEM FOR THE REST OF THEIR
LIVES AS WELL AND QUESTION
BECOMES SORT OF, WELL, WHAT IS
THE IMPACT ON HEALTH IF YOU TAKE
IT FOR A PERIOD OF TIME AND
QUESTION ABOUT LEGACY EFFECT.
IS THAT LEGACY EFFECT PRESENT?
IS THERE STILL BENEFIT HAVING
TAKEN IT FOR A SHORT PERIOD OF
TIME OR YOU KNOW I HAVE BEEN
CONCERNED ABOUT THE POTENTIAL
INFLUENCE ON APPETITE, ET
CETERA, AFTER STOPPING A GLP-1
AND WONDERING WHETHER THE
REBOUND BEHAVIORAL EFFECTS OF
COMING OFF GLP-1S COULD LEAD TO
A SORT OF OVERCORRECTION OF
WEIGHT WHERE YOU END UP GAINING
WEIGHT BEYOND WHERE YOU WERE
INITIALLY AS A RESULT OF
CHALLENGE OF DEALING WITH
WITHDRAWAL FROM BEING ON A
GLP-1. IT WOULD BE INTERESTING
TO SEE WHETHER REAL WORLD DATA
CAN SHOW THAT AND THIS KIND OF
INFLUENCE OF WEIGHT CYCLING AND
REPEATED EPISODES OF BEING
EXPOSED TO MEDICATIONS AND NOT
BEING ON THEM.
THERE HAS BEEN SOME EVIDENCE
ABOUT WEIGHT CYCLING RELATED
HARMS IN LITERATURE AND THINK
MAYBE THERE IS SOME MORE WEIGHT
CYCLING RELATED HARMS THAT COULD
BE INTRODUCED BY MEDICATIONS AND
MEDICATION CHANGES THAT ARE
HAPPENING.
ANYTHING ELSE IN THE CHAT COMING
IN THAT -- OH, GREAT COMMENT
HERE FROM CAROLINE ABOUT LOSS OF
LEAN MASS THAT IS AN INCREDIBLY
IMPORTANT ONE AND THANK YOU FOR
CALLING IT OUT AND LONG INTERM
IMPACT ON FRAILTY FRACTURES,
THANK YOU. GREAT AND VERY
IMPORTANT TO BRING THAT IN AS
WE
WELL.
JUMPING TO THE NEXT SECTION DR.
KING THANK YOU FOR YOUR COMMENT
ON FRAILTY AS WELL AND LIFESTYLE
WE HEARD ABOUT THAT FROM KATIE
ROBINSON EARLIER ABOUT LOOKING
AT PHYSICAL ACTIVITY IN THIS
SPACE IN ADDITION TO DIET
NUTRITIONAL COMPONENTS AND
INFLUENCE ON OUTCOMES AND OTHER
QUESTIONS OR CONCERNS ABOUT
LIFESTYLE INTERVENTIONS?
OLDER ADULT POPULATIONS THAT
VIRGINIA AND RAY PUT IN THE CHAT
ABOUT THAT AND CROSS-CUTTING
CONCERN THAT MAYBE WE COULD
INCORPORATE THAT IN SAME SLIDE
AS PEDIATRIC PREGNANCY IN OLDER
ADULTS OF SPECIAL POPULATION AND
CONCERN AND FRAILTY ISSUES BEING
DISCUSSED AND MUSCLE MASS ISSUES
THAT MAY BE MORE IMPORTANT
THERE. SO LOOKING INTO RISK OF
FRACTURES AND RELATED INJURIES
OF FRAILTY AND LOSS OF MUSCLE
MASS IN EARLY ADULT POPULATION
IS A GOOD IDEA. THAT IS A
SEPARATE SUBGROUP. FOLLOWING
HEALTH, YEAH. THANK YOU,
CAROLINE. THAT IS ANOTHER
IMPORTANT POTENTIAL HARM ISSUE
AND WHETHER WE CAN BEGIN TO
TRACK THAT.
UNDER NUTRITION, KATIE, THANK
YOU FOR THAT ONE AS WELL.
THINKING ABOUT MICRONUTRIENT
DEFICIENCIES AND SIMILAR TO
BARIATRIC PATIENTS AND THINK
WHAT IS OFTEN FOUND IS PATIENTS
COME IN MICRONUTRIENT DEFICIENT
AND THINK IT MAY BE, AGAIN, IF
YOU GO INTO AN INTENSIVE WEIGHT
LOSS PROGRAM YOU ARE CONSUMING
MUCH LESS.
IT MAY INFLUENCE YOUR HEALTH
RISK BY INDUCING OR WORSENING
AGGREGATING POTENTIAL
MICRONUTRIENT DEFICIENCIES THAT
IS IMPORTANT FOR A SAFETY
EVALUATION HERE AS WELL.
IT MAY BE THAT YOU KNOW WHILE
BARIATRIC SURGERY HAS
MALABSORBTIVE COMPONENTS TO IT,
NOT ALL OF THEM DO.
SO IT MAY BE THAT THERE IS
CERTAINLY JUST IMPORTANCE OF
SUPPLEMENTS TO HELP IMPROVE
HEALTH OUTCOMES FOR THIS
POPULATION. VIRGINIA POINTS OUT
MANY MEDICATION ABSORPTION
CHANGES AS POTENTIAL HEALTH
EFFECTS AND INTERESTING. I
THINK AS YOUR BODY COMPOSITION
IS CHANGING AND BODY WEIGHT IS
CHANGING, IT COULD INFLUENCE
CERTAIN MEDICATIONS.
[INDISCERNIBLE] IS A GOOD
EXAMPLE AND MENTAL HEALTH
MEDICATIONS, YES.
SO THINKING ABOUT SAFETY RELATED
TO DOSING OF OTHER MEDICATIONS
AND IF YOU HAVE SIGNIFICANT
WEIGHT LOSS. THANK YOU FOR THAT
PARTICULARLY. NEXT SECTION TO
DATA LINKAGE LOSS AND
INTERESTING OPPORTUNITY AND
ANYBODY HAVE IDEAS ON DATA
LINKAGE FRONT?
>> SOME COMMENTS BY DR. WI AND
WILKINS ABOUT CHALLENGES OF
DOING MULTINATIONAL DATABASED
STUDIES BECAUSE OF
HETEROGENEITY.
>> YES.
>> HAVING MORE DATA IS BETTER
BUT COMPLICATES THINGS THERE IS
ISSUES AND DATA ISSUES WE HAVE
TO PAY ATTENTION TO.
>> YEAH.
>> CAN I EXPAND ON THAT A BIT IF
THAT IS ALL RIGHT?
>> YEAH.
>> YEAH. SO I THINK THAT THE
REASON WHY I THINK IT IS A
BIGGER ISSUE THAT INITIALLY
MEETS THE EYE IS THAT WE KNOW
THAT CERTAIN COUNTRIES MAYBE
HAVE CERTAIN PREFERENCES FOR ONE
TREATMENT VERSUS THE OTHER.
AND FOR PARTICULARLY FOR
OUTCOMES THAT WHAT I WOULD CALL
SOFTER LIKE DEMENTIA OR
PSYCHOLOGICAL FUNCTIONING WHERE
IT IS VERY DISCRETIONARY AND
WHETHER OR NOT YOU SORT OF DO A
SCREENING OR ASSESSMENT THAT
THAT IS A HUGE CONFOUNDER.
SOMETIMES WHEN YOU SEE A
DIFFERENCE TRACKING WITH ONE
TREATMENT OR ANOTHER, IT MIGHT
JUST BE BECAUSE THE INITIATION
OF THAT ONE TREATMENT IS
PREFERENTIAL IN ONE COUNTRY THAT
ALSO HAS A SORT OF DIFFERENTIAL
ASSESSMENT OF WHATEVER OUTCOME
AND IS A POINT THAT I'M TRYING
TO MAKE. IT IS NOT TRIVIAL.
WE HAVE REJECTED LOTS OF PAPERS
WHERE THERE ARE SOME DATA SETS
WHERE THAT IS A COMPLETE BLACK
BOX IN TERMS OF WHAT COUNTRIES
ARE CONTRIBUTING AND WHERE DATA
IS COMING FROM.
ANYWAY, THANK YOU FOR THE
OPPORTUNITY FOR ME TO MAKE THAT
POINT.
>> GREAT. THANK YOU, KRISTINA.
YEAH. THERE IS CLEARLY SOME
DATA SETS THAT MIGHT BE SUPERIOR
FOR TRYING TO TRACK SOME ISSUES
OVER OTHERS AND SO IF THOSE ARE
OF MAJOR CONCERN, IT IS -- IT IS
DEFINITELY PART OF THE TARGET
TRIAL THINKING ABOUT INITIATION
AND THOSE KINDS OF ELIGIBILITY
PARAMETERS.
YOU KNOW?
GREAT.
I THINK ONE LAST SLIDE THERE
AROUND METHOD LOGIC ISSUES THAT
WE TOUCHED ON A BIT ABOUT -- WE
ARE COMING TO THE TOP OF THE
HOUR AND WANT TO CLOSE MYSELF BY
SAYING THIS WAS FANTASTIC AND
THINK THAT THE PRESENTATIONS
OVER THE LAST TWO DAYS WERE
OUTSTANDING.
SPEAKERS, MODERATORS,
DISCUSSIONS AS WELL.
IT JUST HAS CREATED A RICH SORT
OF DATABASE, ESSENTIALLY OF GAPS
AND OPPORTUNITIES FOR US TO
ADDRESS GOING FORWARD.
I PERSONALLY LOOK FORWARD TO
SEEING THE KINDS OF RESEARCH
THAT WILL COME OUT AS A RESULT
OF THIS AND THINK THAT SHARING
OF ALL THESE BEST PRACTICES WILL
LEAD TO STRONGER STUDIES AND
MORE RIGOROUS PEER REVIEW, ET
CETERA, THAT REALLY HELPS TO
PUSH THE FIELD FORWARD.
THERE IS MAJOR GAPS THAT REAL
WORLD DATA WILL BE ABLE TO
ADDRESS SEPARATE FROM CLINICAL
TRIALS AND LET'S -- I'M EXCITED
TO SEE WHAT IT LOOKS LIKE AND
WHAT OTHER CLOSING REMARKS WOULD
YOU HAVE?
>> I WILL ECHO YOUR THANKS TO
EVERYONE FOR JOINING US AND THAT
Q & A AND QUESTIONS THROUGHOUT
WERE SUPERB AND HELPS US TO
REALLY GET TO EVEN DEEPER ISSUES
THAN RAISED IN THE EXCELLENT
PRESENTATIONS AND THANKS FOR
YOUR ENGAGEMENT.
DARREN?
>> YEAH. I WANT TO THANK
PARTICIPANTS AND THE DISCUSSION
WAS GREAT AND ORGANIZERS AND ALL
OF THE SPEAKERS AND MODERATORS
THIS IS ONE OF THE BEST VIRTUAL
MEETINGS I HAVE BEEN PART OF AND
LOGISTICS HAVE BEEN GREAT. LOTS
OF PEOPLE MAKE IT HAPPEN BEHIND
THE SCENES. THANK YOU.
>> COORDINATING IT FROM BEHIND
THE SCENES AND DIDN'T RUN
SEAMLESSLY THANK YOU AND TURNING
TO CRAIG TO HELP US CLOSE IT
OUT.
>> THANK YOU. THANK YOU TO
EVERYONE FOR THE WORKSHOP WITH
SUCH AN IMPORTANT
[INDISCERNIBLE] OF GAPS AND
OPPORTUNITIES.
AND THERE IS A LOT OF THEM.
HIGHLIGHTING ALL OF THESE
IMPORTANT TOPICS, LIKE YOU SAID
THEY WILL HELP MOVE THE FIELD
FORWARD IMPROVING UNDERSTANDING
OF GLP-1 BASED MEDICATIONS AND
PREVENTING AND TREATING SEVERAL
CHRONIC DISEASES AND OVER THE
LAST FEW DAYS CO-CHAIRS AND
SPEAKERS AND MODERATORS HAVE
REALLY DONE A FANTASTIC JOB OF
MEETING THE OVERALL GOAL OF THE
WORKSHOP THAT IS TO IDENTIFY HOW
REAL-WORLD EVIDENCE CAN HELP
FILL KNOWLEDGE GAPS ABOUT USING
GLP-1 BASED MEDICATIONS CLINICAL
PRACTICE CLINICAL GUIDELINES AND
HEALTHCARE POLICY AND SHINED ON
TOUGH METHODOLOGICAL CHALLENGES
AND OFFER EFFECTIVE STRATEGIES
HOW TO DEAL WITH CHALLENGES.
I JUST WANTED TO MAKE SURE THAT
EVERYONE KNOWS THAT VIDEO OF THE
WORKSHOP AND EXECUTIVE SUMMARY
WILL BE POSTED TO THE WORKSHOP
WEBSITE.
AND AS WE GET READY TO ADJOURN
THE WORKSHOP I ALSO WOULD LIKE
TO THANK EVERYONE WHO MADE THE
WORKSHOP A SUCCESS AND STARTING
WITH NIDDK CO-ORGANIZERS DR.
ZABULA AND [INDISCERNIBLE].
AND FEDERAL PLANNING COMMITTEE
FROM ACROSS NIH AND HHS AND TO
THE WORKSHOP CO-CHAIRS SUCH AS
DAVID AND KURTIS AND DARREN AND
HUGE THANK YOU FOR SHARING YOUR
VALUABLE TIME AND EXPERTISE TO
DEVELOPING THIS WORKSHOP IN THE
PAST SEVERAL MONTHS AND THANK
YOU TO THE SPEAKERS AND
MODERATORS FOR INCREDIBLY
INSIGHTFUL PRESENTATIONS AND
ENGAGING DISCUSSION ON
INTERSECTION OF GLP-1-BASED
THERAPIES AND REAL-WORLD
EVIDENCE AND THANK YOU TO DANIEL
OF SCIENTIFIC CONSULTING GROUP
FOR MAKING THE WORKSHOP RUN SO
SMOOTHLY AND ATTENDEES FOR
CONTRIBUTING HELPFUL QUESTIONS
AND COMMENTS ON THE IMPORTANT
TOPIC AND WITH THAT I WILL CLOSE
THE MEETING AND HAVE A GOOD
MEETING, EVERYONE.
TAKE CARE.