>>>GOOD MORNING, IT'S A PLEASURE
TO BE ABLE TO PRESENT HERE TO
THE ADVISORY COMMITTEE AND IT'S
ALWAYS NICE TO SEE SO MANY
FRIENDS AND COLLEAGUES HERE OIN
LITTLE BIT TRIVALENT LIVE
ATTENUATED FLU
INACTIVATED INFLUEN THE COMPARA
SAFETY STUDIES IN CHILDREN.
WE WERE REALLY CHARGED WITH
TRYING TO ASSIST THE G.R.A.D.E.
PROCESS IN DOING AN EVIDENCE
REVIEW FOR FLU VACCINE SAFETY IN
CHILDREN 2-8 YEARS OF AGE.
THIS WORK WAS DONE BY A
COLLABORATIVE GROUP CALLED THE
PEDIATRIC FLU VACCINES SAFETY
EVIDENCE REVIEW GROUP.
IT CONSISTS OF FOLKS FROM THE
CDC, AND FOLKS FROM THE CLINICAL
IMMUNIZATION SAFETY ASSESSMENT
PROJ CISA.
I DON'T KNOW HOW MANY OF YOU
ARE FAMILIAR WITH CISA, IT'S A
NETWORK OF FOLKS FROM THE
IMMUNIZATION SAFETY OFFICE AND
SEVEN RESEARCH CENTERS.
>> CHARGED WITH DOING A VACCINE
SAFETY PUBLIC HEALTH SERVICE.
WE DO INVESTIGATIONS, RESEARCH
STUDIES RELATED TO VACCINE
SAFETY, REVIVE REVIEW ADVERSE E
AT SAFETY ISSUES REGARDING
IMMUNIZATIONS, SO THIS FOLLOWS
UNDER THAT RUBRIC.
>>> JUST TO LOOK AT POTENTIAL
DISCLOSE YURES FOR CONFLICT OF
INTEREST, I MUST BE MORE
CONFLICTED THAN MY COLLEAGUES
FROM VANDERBILT SO OUR
OBJECTIVES WERE TO EVALUATE THE
EVIDENCE FOR THE SAFETY OF
TRIVALENT LIVE ATTENUATED FLU
VACCINE COMPARED WITH TRIVALENT
INACTIVATED FLU VACCINE IN
CHILDREN AGE 2-8 YEARS OF AGE,
USING THE ACIP GRADING
RECOMMENDATIONS OR THE
G.R.A.D.E. PROCESS.
AND I THINK LISA IS GOING TO,
THIS IS KIND OF A SEGUE TO
LISA'S TALK.
SO THE ACIP FLU WORKING GROUP
CAME UP WITH AN ASSESSMENT MUCH
AS LISA SHOWED FOR OUTCOMES FOR
EFFICACY, WE, THEY SET SOME
GUIDELINES FOR CHOSE OUTCOMES
FOR SAFETY ANALYSIS, AMONG THESE
WERE IMMEDIATE HYPERSENSITIVITY
IN ANAPHYLAXIS.
FEBRILE SEIZURE, MEDICALLY
ATTENDED WHEEZING, SYNDROME,
OTHER RESPIRATORY OUTCOMES AND
SYMPTOMS.
THESE GRADED FOUR OF THESE AS
HAVING CRITICAL IMPORTANCE, AS
TWO AS BEING IMPORTANT.
NOW, WE TOOK OF THESE SAFETY
OUTCOMES, AND DISCUSSED THEM
INTENSIVELY AND IN OUR SMALLER
WORKING GROUP AND ALSO IN THE
LARGER CISA WORKING GROUP.
AND SOME OF THESE OUTCOMES, THE
LAST TWO BEING OTHER NEUROLOGIC
OUTCOMES AND RESPIRATORY
SYMPTOMS, WHICH WERE GRADED AS
IMPORTANT, WERE REALLY FAIRLY
NONSPECIFIC.
SO WE ACTUALLY DID NOT KEEP THEM
TO, FOR OUR FINAL SAFETY
ANALYSIS.
WE DID LOOK AT ANAPHYLAXIS AND
FEBRILE SEIZURES, WE DID NOT
SELECT THEM FOR THIS REVIEW.
FOR SEVERAL REASONS.
MOSTLY BECAUSE THESE EVENTS ARE
FAIRLY RARE OR UNCOMMON.
AND IF YOU'RE LOOKING AT THE
COMPARATIVE STUDIES, LOOKING AT
LAIV, VERSUS IIV, THERE'S
LIMITED INFORMATION FOR REVIEW.
WE DECIDED TO KEEP MEDICALLY
ATTENDED WHEEZING AS AN OUTCOME
FOR REVIEW, BECAUSE THIS IS
COMMON AND CLINICALLY IMPORTANT.
AGAIN, GUILLEN BAR SYNDROME,
THERE'S NONE FOR REVIEW IN THE
STUDIES COMPARING LAIV AND IIV.
FEVER WAS ADDED AS AN OUTCOME
FOR THESE STUDIES, BECAUSE IT'S
COMMON, IT'S MEDICALLY
IMPORTANT, IT'S SOMEWHAT
COMPARABLE ACROSS THE STUDIES.
AND IT'S A POTENTIAL PROXY FOR
FEBRILE SEIZURE RISK.
SO WE ADDED THAT AS AN OUTCOME.
AND WE ADDED CERTIFICATE JUST
ADVERSE EVENTS AS AN OUTCOME.
WE CONSIDERED IT IMPORTANT, IT'S
BEEN USED IN OTHER SAFETY
REVIEWS.
AND INCLUDES SOME OF THE THESE
RARE AND LESS-COMMON EVENTS.
WHEN YOU'RE LOOKING AT THE
STUDIES FOR LAIV VERSUS IIV.
>> SO THE METHODS THAT WE USED
FOR OUR EVIDENCE REVIEW, THERE
WERE EIGHT PUBLICATIONS THAT
DIRECTLY COMPARED LAIV TO IIV 3.
THAT WERE SELECTED FOR REVIEW.
THESE MANUSCRIPTS WERE USED
USING GRADING SHEETS, OUTCOME
DEFINITION, STUDY DESIGN, THE
SEASON IN WHICH THE STUDIES WERE
CONDUCTED, AGES OF THE STUDY
POPULATION.
AND SAMPLE SIZE.
WE ALSO THEN LOOKED AT
LIMITATIONS OR POTENTIALS FOR
BIASES AND THE RANDOMIZED
TRIALS.
WE LOOKED AT ALLOCATION
CONCEALMENT.
BLINDING, LOSS OF FOLLOW-UP,
FAILURE TO ADHERE TO INTENTION
TO TREAT ANALYSIS.
STOPPING EARLY FOR BENEFIT OR
FAILURE TO REPORT AN OUTCOME.
FOR THE OBSERVATIONAL STUDIES,
WE LOOKED TO SEE IF THE STUDIES
FAILED TO APPLY OR DEVELOP
APPROPRIATE ELIGIBILITY
CRITERIA.
IF THERE WERE FLAWED MEASURES
FOR EXPOSURES OR OUTCOMES.
OR FAILURES TO CONTROL FOR
CONFOUNDING.
WE ALSO GRADED OR LOOKED AT EACH
STUDY FOR INDIRECTNESS IN TERMS
OF THE POPULATION, THE
INTERVENTION OR TO SEE WHETHER
THE OUTCOME OR INTERVENTION
DIFFERED FROM THAT OF INTEREST
OR TO SEE IF THE VACCINES
COMPARED WITH EACH OTHER OR WITH
PATELLA TE
PLACEBO OR NOT ONE ANOTHER.
REVIEWED
WITHIN THE PEDIATRIC SAFETY
GROUP AND THE CISA INVESTIGATORS
AND ALSO HAVE BEEN REVIEWED WITH
THE ACIP FLU WORKING GROUP.
SO AMONGST THE TRIALS, THERE
WERE THREE THAT WERE INITIALLY
CHOSEN, BUT THEN WERE EXCLUDED
FOR VARIOUS REASONS FROM THE
SAFETY ASSESSMENT.
THERE WAS THE CLOVER STUDY,
WHICH WAS CONDUCTED YEARS 86,
87, POPULATION OF CHILDREN 3-19
YEARS OF AGE.
IT WAS A DOUBLE-BLIND
PLACEBO-CONTROLLED STUDY.
OF AROUND 200 CHILDREN.
COMPARING IIV AND NASAL PLACEBO
TO SAILEN PLACEBO AND BIVALENT
LAIV.
HOWEVER NO SAFETY OUTCOMES
DESCRIBED IN THAT STUDY.
WE ELIMINATED IT FROM OUR SAFETY
ASSESSMENT.
KATHY NEWSLE'S STUDY PREVIOUSLY
MENTIONED, WAS CONDUCTED OVER A
FIVE-YEAR PERIOD.
IT WAS INITIALLY CONDUCTED IN
PERSONS BETWEEN 1-65 YEARS OF
AGE.
HER REPORT REPORTED ON SUBJECTS
UNDER 16 YEARS OF AGE.
IT WAS A RANDOMIZED CONTROLLED
TRIAL.
HOWEVER IF YOU'RE LOOKING AT THE
OUTCOMES OF INTEREST, IN THE
MANUSCRIPT, ONLY FEVER WAS
DESCRIBED AS ONE OF THE
OUTCOMES.
AND THE STUDY WAS A LITTLE
PROBLEMATIC IN DOING COMPARISONS
IN THAT THE GROUP 2 WHO RECEIVED
THE LAIV ONLY CONTAINING TWO FLU
A STRAINS, ALSO RECEIVED AN
INACTIVATED MONOVALENTB STRAIN,
SO YOU COULDN'T DO A
HEAD-TO-HEAD COMPARISON.
SO WE OMITTED IT FROM OUR
ANALYSIS AS WELL.
THE LAST STUDY, WHO WIHOLLARHN
OPEN-LABEL COMMUNITY-BASED
INTERVENTION IN CHILDREN 5-18
YEARS OF AGE.
A FAIRLY LARGE NUMBER OF
SUBJECTS, BUT OUR SAFETY
OUTCOMES WERE NOT DESCRIBED IN
THIS STUDY.
SO THAT LEFT FIVE EVALUATIONS
FOR OUR SAFETY ASSESSMENT.
SOME OF THESE YOU'VE HEARD
MENTIONED TODAY.
THE ASHKANAZI STUDY AND THE
FLEMING STUDY ARE FAIRLY
COMPARABLE STUDIES, DONE IN THE
SAME YEAR OR SAME SEASON.
THE ASHKANAZI STUDY WAS DONE IN
YOUNGER CHILDREN WHO HAD
RECURRENT RESPIRATORY TRACT
INFECTIONS.
WHEREAS THE FLEMING STUDY WAS
DONE IN CHILDREN OF-THE-6-17
YEARS OF AGE WITH ASTHMA.
THEY WERE BOTH OPEN-LABEL
RANDOMIZED STUDIES.
ABOUT THE SAME NUMBER OF
SUBJECTS, 2,000 IN EACH STUDY.
AND CHILDREN AND ADOLESCENTS
WERE RANDOMIZED TO GET EITHER
IIV 3, OR LAIV.
THE BELSHI ARTICLE OR PAPER
DESCRIBED STUDIES DONE IN THE
YEARS 2004 AND 2005.
IT WAS CONDUCTED IN CHILDREN
6-59 MONTHS OF AGE.
AND THIS STUDY DID INCLUDE SOME
CHILDREN WITH WHEEZING OR
HISTORY OF ASTHMA.
IT DIDN'T EXCLUDE THOSE
CHILDREN.
IT WAS A DOUBLE-BLIND
PLACEBO-CONTROLLED STUDY.
WHERE CHILDREN RECEIVED EITHER
IIV AND LAIV PLACEBO, OR
RECEIVED IIV 3 PLACEBO AND LAIV.
AND AROUND 8,000 OR MORE
CHILDREN WERE ENROLLED IN THAT
STUDY.
THE LAST TWO STUDIES WERE MORE
OBSERVATIONAL STUDIES.
CONDUCTED OVER SLIGHTLY
DIFFERENT TIME PERIODS.
THE TOBAK STUDY WAS AN
OBSERVATIONAL STUDY IN YOUNGER
CHILDREN.
24-59 MONTHS OF AGE.
WHERE AS THE BAXTRA STUDY
INCLUDED CHILDREN IN A SLIGHTLY
OLDER AGE RANGE.
THESE WERE OBSERVATIONAL STUDIES
DONE MOSTLY THROUGH THE KAISER
SYSTEM AND INCLUDED FAIRLY LARGE
STUDY POPULATIONS.
IF YOU LOOK AT OUR OUTCOMES OF
INTEREST, FEVER, MEDICALLY
ATTENDED WHEEZING AND SERIOUS
ADVERSE EVENTS, THE FIRST THREE
STUDIES DESCRIBE THOSE AS
OUTCOMES, THE LAST TWO STUDIES
CAN BE USED TO LOOK AT MEDICALLY
ATTENDED WHEEZING AND SERIOUS
ADVERSE EVENTS.
SO WE SET OUT TO DO THIS, AND
THOUGHT, WELL WE'LL START
TACKLING THIS BY LOOKING AT
FEVER, THINKING THAT THAT WOULD
BE A FAIRLY SIMPLE OUTCOME TO
LOOK AT.
WELL, IT'S MUCH LIKE THE DUKE
SYRACUSE BASKETBALL GAME, KIND
IS A LITTLE UP TO
INTERPRETATION, WAS IT A BLOCK
OR A CHARGE?
I HAPPEN TO THINK IT WAS A
CHARGE.
BUT ANYWAY, MOVING ON, FEVER WAS
DESCRIBED SOMEWHAT DIFFERENTLY
IN EACH STUDY.
SO IF YOU LOOK, EACH OF THESE
ARTICLES DID DESCRIBE FEVER.
THE MEASUREMENTS WERE DIFFERENT
FROM STUDY TO STUDY.
IT WAS AXILLARY OR RECTAL, ORAL
OR AXILLARY, ORAL OR RECTAL
DEPENDING UPON THE STUDY.
THE MEASUREMENT INTERVALS
DIFFERED FROM STUDY TO STUDY.
TEN DAYS UP TO 15 DAYS.
AND THE METHODS WHAT THEY
DESCRIBE AS HOW THEY MEASURED
FEVER IT WAS A LITTLE BIT
DIFFERENT THAN HOW THEY
DESCRIBED FEVER IN THE RESULTS,
SO FROM PAPER TO PAPER, THEY
WERE QUITE DIFFERENT
DESCRIPTIONS OF FEVER.
MAKING IT A LITTLE BIT MORE
CHALLENGING.
HOWEVER, IF YOU LOOK AT THE
OUTCOMES, YOU CAN DIRECTLY
COMPARE IN EACH OF THE STUDIES,
CHILDREN RECEIVED LAIV TO
CHILDREN WHO RECEIVED TIV.
SO FOROR THE FIRST PAPER, THE
ASHKANAZI PAPER, T ERATURE DURI
11-DAY PERIOD.
IF YOU LOOK AT TEMPERATURE
ELEVATIONS OVER37.5 AND 38.6,
YOU CAN SEE AFTERND
DOSES 2, NO SIGNIFICANT
DIFFERENCES BETWEEN THE LAIVGRO.
IN THE FLEMING PAPER, LOOKED AT
THE FEVER OVER A 15-DAY PERIOD.
THEY REPORTED FOUR DIFFERENT
LEVELS OF FEVER.
REMEMBER, THESE WERE OLDER
CHILDREN.
ONLY RECEIVED A SINGLE
OFE.
AND LOOKING AT THE COMPARISONS,
AGAIN NO OBSERVED DIFFERENCES
BETWEEN CHILDREN WHO RECEIVED
CHILDREN WHO
AT THAT POINT, TIV OR IIV.
THE LAST PAPER DID OBSERVE SOMEE
BELSHI ARTE IS ONLY THEPAPER AS.
IF YOU LOOK AT THE BLA
APPLICATION, ACTUALLY IT IS
BROKEN OUT.
OVER SEVERAL DAY
SEVERAL-DAY PERIE IN THE PAPERSD
DAY TWO OF FEVER, AFTER THE ANT
LOW OR FEVER OVER 37.8,
THERE WAS A SIGNIFICANT
5.4% IN CHILDREN WHO ER
GOT LAIV, VERSUS 2% IN CHILDR
WHO GOT THE TIV.
FOR HIGHER FEVERS OVER 38.9,
THERE WAS NO DIFFERENCE
REPORTED.
SO IN GRADING THE EVIDENCE, WE
LOOKED AT THE FOUR PAPERS, THE
ASHKANAZI PAPER, THE POPULATION
DIFFERED A LITTLE BIT FROM THAT
OF INTEREST.
IT WAS SOME OF THE CHILDREN WERE
YOUNGER.
THESE WERE CHILDREN WHO HAD
RECURRENT RESPIRATORY TRACT
INFECTIONS.
FOR THE FLEMING PAPER, IT WAS
DOWNGRADED SOMEWHAT, BECAUSE
THESE WERE SOME OF THESE
CHILDREN WERE OLDER.
THEY ALSO INCLUDED ASTHMA
CHILDREN.
AND IN THE BELSHI PAPER, SOME
WERE YOUNGER AND NONE OF THE
CHILDREN WERE IN THE SIX TO 96
MONTHS AGE RANGE IN THE
POPULATION OF INTEREST, WHICH IS
2-8 YEARS OF AGE.
IN TERMS OF GRADING THE EVIDENCE
FOR LIMITATIONS AND POTENTIAL
FOR BIASES FOR A RANDOMIZED
TRIAL, FOR ASHKANAZI AND
FLEMING, WE DOWNGRADE A LITTLE
BIT.
BECAUSE THEY WERE NOT BLINDED
STUDIES.
AND ALL THREE OF THE STUDIES
THERE WAS SOME LOSS TO
FOLLOW-UP.
FOR WHICH IT DOWNGRADE THE
EVIDENCE A LITTLE BIT.
MOVING ON TO OUR SECOND OUTCOME
OF INTEREST.
MEDICALLY ATTENDED WHEEZING.
THESE DEFINITIONS ARE A LITTLE
BIT DIFFERENT FROM STUDY TO
STUDY.
AS WELL, MAKING IT A LITTLE BIT
DIFFERENT TO COMPARE BETWEEN THE
STUDIES.
THE ASHKANAZI PAPER DEFINED
WHEEZING EPISODES OBSERVED BY
MEDICAL PRACTITIONER.
FLEMING INCIDENTS OF ASTHMA
EXACERBATION ACUTE WHEEZING,
ILLNESS ASSOCIATED WITH
HOSPITALIZATION, ANY UNSCHEDULED
CLINIC VISIT OR NEW PRESCRIPTION
INCLUDING RESCUE MEDICATION.
AND BELSHI ASCRIBED MEDICALLY
ATTENDED WHEEZING AS PRESENCE OF
WHEEZING ON PHYSICAL EXAM,
CONDUCTED BY A HEALTH CARE
PROVIDER, WITH A PRESCRIPTION
FOR BRONCO DIAL ATOR, HE E ORAT
RESPIRATORY DISTRESS.
AND ATHS MARKS REACTIVE AIRWAY
DISEASE, ENCOMPASSING
INDIVIDUALS WITH A DIAGNOSIS OF
ASTHMA, COUGH VARIANT ASTHMA,
EXERCISE-INDUCED ATHS MAXT THE
TERM WHEEZING OR SHORTNESS OF
BREATH, INCLUDING THE DIAGNOSIS
OF WHEEZING AND DYSAPNEA AND
SHORT NEZ OF BREATH.
THE TIME INTERVALS DID DIFFER A
LITTLE BIT FROM PAPER TO PAPER.
ASHKANAZI ADMITTED THE FIRST TEN
DAYS AFTER THE DOSING IN THEIR
OBSERVATION PERIOD WHICH ONE
MIGHT CONSIDER AN IMPORTANT TIME
INTERVAL.
TO LOOK FOR MEDICALLY ATTENDED
WHEEZING AFTER DOSING.
FLEMING LOOKED AT THE 42 DAYS
AFTER EACH DOSE AS DID BELSHI
AND TOBAK AND BAXTER.
THE RESULTS REPORTED FOR EACH OF
THESE STUDIES ARE REPORTED A
LITTLE BIT DIFFERENTLY THIS WAS
A LITTLE BIT CONFUSING TO TRY TO
TEASE THROUGH.
BUT IF YOU LOOK FOR THE
ASHKANAZI AND FLEMING PAPERS,
THEY LOOKED AT THE PERCENT
DIFFERENCE IN WHEEZING BETWEEN
THE LAIV GROUPS AND THE TIV
GROUPS.
AND THEY DID NOT OBSERVE ANY
DIFFERENCE IN WHEEZING EPISODES
BETWEEN EITHER OF THEIR GROUPS
FOR THESE PAPERS.
AFTER THE FIRST DOSE AND FOR
ASHKANAZI PAPER AFTER THE SECOND
DOSE.
BELSHI REPORTED ADJUSTED RATE
DIFFERENCES BETWEEN, IN WHEEZING
BETWEEN THE LAIV GROUP AND OR
DIFFERENCE BETWEEN THE LAIV
GROUP AND THE TIV GROUP.
AND YOU CAN SEE HERE THERE WAS
SOME DIFFERENCE IN THE OVERALL
GROUP.
BUT WHEN YOU AGE STRATIFY, MOST
OF THAT DIFFERENCE IS REALLY IN
THOSE CHILDREN, AS WE ALL KNOW,
UNDER 24 MONTHS OF AGE.
WITH THE DIFFERENCE BEING 1.18%.
THIS HELD TRUE FOR THOSE WHO
WERE UNPREVIOUSLY UNVACCINATED,
NOT IN THOSE WHO HAD BEEN
PREVIOUSLY VACCINATED.
AND NOT AFTER A SECOND DOSE.
>> HERE'S WHERE IT BECOMES MORE
PROBLEMATIC.
LOOKING AT THE OBSERVATIONAL
STUDIES.
THEY LOOKED AT HAZARD RATIOS,
COMPARING RATES OF WHEEZING OR
MEDICALLY ATTENDED WHEEZING IN
CHILDREN AFTER RECEIVING LAIV OR
IIV.
AND YOU CAN SEE HERE, WHEN
YOU'RE COMPARING IN THE HAZARD
RATIOS, YOU'RE GETTING HAZARD
RATIOS OF .38, COMPARING LAIV TO
IIV.
MEANING A LOWER RATE IN THE LAIV
GROUP TO THE IIV GROUP.
AND THIS WAS TRUE FOR BOTH THE
BAM TER ANDBAXTER AND TOEBIC
COMPARIS
COMPARISONS.
IT HAS TO DO MOSTLY WITH THE
CURRENT RECOMMENDATIONS WITH HOW
WE GIVE TIV AND LAIV.
MEANING LAIV IS NOT RECOMMEND
FORD CHILDREN WHO HAVE
UNDERLYING MEDICAL CONDITIONS,
SUCH AS ASTHMA.
SO NATURALLY YOU WOULD EXPECT
WHEEZING EPISODES TO OCCUR IN A
HIGHER RATE IN THE IIV GROUP.
SO THESE DATA ARE CONFOUNDED.
GRADING THE EVIDENCE, AGAIN
THESE LOOKING ARE PRETTY SIMILAR
TO WHAT WE LOOKED AT BEFORE.
POPULATION DIFFERS FROM THAT OF
INTEREST.
YES, FOR ASHKANAZI, FLEMING AND
BELSHI.
ADDING THE TOEBIC AND BAXTER
PAPERS.
TOEBIC, THE POPULATION DIFFERED
A LITTLE BIT IN THAT THERE WERE
NONE OF THE CHILDREN WERE
BETWEEN SIX AND 96 MONTHS OF AGE
AND THE BAXTER PAPER, NONE OF
THE CHILDREN WERE BETWEEN 24 AND
59 MONTHS OF AGE.
THEN IF WE DOWNGRADE THE
EVIDENCE A LITTLE BIT FOR THE
ASHKANAZI PAPER, AS I MENTIONED
BECAUSE MEDICALLY ATTENDED
WHEEZING WASN'T REPORTED IN THE
FIRST TEN DAYS AFTER RECEIPT OF
THE VACCINE DOSE.
IF YOU LOOK AT OTHER LIMITATIONS
FOR THE RANDOMIZED TRIALS,
AGAIN, THIS LOOKS FAMILIAR TO
THE LAST SLIDE.
ASHKANAZI AND FLEMING WERE NOT
BLINDED, THERE WAS LOSS TO
FOLLOW-UP IN THE THREE STUDIES.
IF YOU ARE LOOKING AT THE
OBSERVATIONAL STUDIES, AS I
ALREADY MENTIONED, TOEBIC AND
BAXTER CAN BE DOWNGRADED FOR
FAILURE TO CONTROL CONFOUNDING
THIS BRINGS ME TO THE LAST
OUTCOME OF INTEREST, SERIOUS
ADVERSE EVENTS AS AN OUTCOME.
AGAIN, THE DEFINITIONS, SOMEWHAT
DIFFER OR IN SOME OF THE PAPERS
REALLY WEREN'T WELL DESCRIBED.
WHAT, WHATN'T A SERIOUS
ADVERSE EVENT.
BUT FOR THE FLEMING AND BELSHI
PAPER, I THINK THESE ARE FAIRLY
STANDARD DEFINITIONS.
THE TIME INTERVALS FOR LOOKING
AT SERIOUS ADVERSE EVENTS WERE
FOR MOST OF THE STUDIES, AT THE
FROM THE TIME OF ENROLLMENT
THROUGH THE INFLUENZA
SURVEILLANCE PERIOD FOR THE
OBSERVATIONAL STUDIES FOR TOEBIC
AND BAXSTER.
IT WAS IN THE 0-42 DAYS POST
VACCINATION.
RELATEDNESS IN MOST ALL OF THESE
STUDIES WAS DETERMINED.
THE CATEGORIES RANGED FROM
POSSIBLY, PROBABLY OR
POTENTIALLY.
AND THEY WERE ALL DETERMINED AS
PER INVESTIGATOR IN EACH OF THE
STUDIES.
SO IN LOOKING AT SERIOUS ADVERSE
EVENTS, RATES WERE FAIRLY
COMPARABLE BETWEEN IN THE
ASHKANAZI PAPER, BETWEEN THE
LAIV GROUP AND THE TIV GROUP.
5.8 AND 4.7%.
THERE WAS A SMALL NUMBER OF
VACCINE ADVERSE EVENTS OR
SERIOUS ADVERSE EVENTS
CONSIDERED RELATED TO STUDY
PRODUCT IN BOTH OF THOSE PAPERS.
IN THAT PAPER, PARTICULAR PAPER.
IN THE FLEMING PAPER, THE RATES
FOR SERIOUS ADVERSE EVENTS WERE
AGAIN COMPARABLE WITH A FEW OF
THESE EVENTS IN THE LAIV GROUP
AND TIV GROUP BEING ASCRIBED AS
RELATED TO THE VACCINE.
AND IF YOU LOOK THERE, THERE WAS
ONE EPISODE IN THE LAIV GROUP OF
PNEUMONIA AND ASTHMA ATTACK ON
DAY TWO THAT WAS CONSIDERED
VACCINE RELATED.
IN THE BELSHI PAPER, THIS ONE
AGAIN REPORTED SIMILAR RATES OF
SERIOUS ADVERSE EVENTS IN BOTH
GROUPS.
THEY DO NOTE IN THE MANUSCRIPT
THAT MOST OF THE SERIOUS ADVERSE
EVENTS WERE HOSPITALIZATIONS,
INTERESTINGLY WHEN YOU LOOK AT
HOSPITALIZATIONS WHICH USUALLY
IN ALL STUDIES CONSTITUTES A
SERIOUS ADVERSE EVENT, THE RATES
WERE FAIRLY SIMILAR, IF YOU LOOK
AT THE WHOLE POPULATION, 3.1%,
AND 2.9%.
WHEN YOU AGE-STRATIFY, LOOKING
AT CHILDREN WHO WERE BETWEEN SIX
AND 11 MONTHS OF AGE, YOU SEE
THAT RATES OF HOSPITALIZATION
I'LL CALL IT HOSPITALIZATION,
WERE HIGHER IN THAT GROUP, 6%,
VERSUS 2.6%.
AGAIN, THIS IS OUTSIDE THE AGE
RANGE OF INTEREST FOR OUR
PARTICULAR EVIDENCE REVIEW.
IF YOU LOOK AT THE OTHER AGE
GROUPS, THERE WERE NO RATE
DIFFERENCES.
IF YOU LOOK AT VACCINE RELATED
SAEs, THERE WERE A FAIR NUMBER
OF RESPIRATORY EVENTS.
POINTED OUT IN YOU CAN POINT OUT
IN THE LAIV GROUP, BRONCO LITIS,
ASTHMA, BREATHING, REACTIVE
AIRWAY DISEASE, THERE WERE CIVIL
IN THE DIV GROUP, PNEUMONIA,
WHEEZING, AND TO POINT OUT, TWO
FEBRILE SEIZURES.
IN THE TOEBIC OBSERVATIONAL
STUDY THE THE RATE OF SERIOUS
ADVERSE EVENTS WAS SLIGHTLY
HIGHER IN THE TIV GROUP.
AGAIN, ONE MIGHT ASCRIBE THAT TO
THE FACT THAT THE TIV GROUP IS
GENERALLY A SICKER POTENTIALLY
SICKER POPULATION.
WITH MORE MEDICAL COMPROMISED OR
UNDERLYING MEDICAL CONDITIONS.
THERE WERE A FEW
VACCINE-RELATED SAEs DESCRIBED
IN THE LAIV GROUP.
ONE WAS A CHILD WITH A RIGHT
MIDDLE LOBE INFILTRATE AND FEVER
AND ONE CHILD WITH INO SUS
SEPARATION IN THE BAXTER ARTICLE
THE RATES FOR SAEs WERE NOT
NOTED TO BE DIFFERENT.
IN THE LAIV GROUP THERE WERE
TWO.
AND ANOTHER CHILD WITH BELL'S
PALSY.
TWO DAYS POST VACCINATION.
LOOKING AT GRADING THE
EVIDENCE, THE POPULATION
DIFFERING FROM THAT OF INTEREST.
IS THE SAME AS PREVIOUSLY
DESCRIBED.
ON FOR THE OTHER OUTCOMES.
AND IF YOU LOOK HERE AT
LIMITATIONS, OF THE OBSERVATION,
RANDOMIZED TRIALS, AGAIN THESE
ARE THE SAME AS DESCRIBED FOR
THE OTHER OUTCOMES.
FOR THE OBSERVATIONAL STUDIES,
THESE STUDIES AGAIN FAILED TO
CONTROL FOR CONFOUNDING, FOR A
SERIOUS ADVERSE EVENTS.
AND FOR THE TOEBIC PAPER, ALL
THE SAEs WERE DESCRIBED AS BEING
DIAGNOSED IN THE HOSPITAL
SETTING, POSSIBLY EXCLUDING SOME
CHILDREN WHO MAY HAVE HAD SAEs
OUTSIDE THE HOSPITAL SETTING.
IN CONDUCTING THIS REVIEW, THERE
WERE SEVERAL LIMITATIONS, A FEW
STUDIES THAT DIRECTLY COMPARE
LAIV VERSUS IIV.
SEVERAL OF THE STUDIES DIDN'T
ASSESS OUTCOMES OF INTEREST.
THE DEFINITIONS FOR THE OUTCOMES
OF INTEREST ARE NOT
STANDARDIZED, WHICH IS A
PARTICULAR PROBLEMS FOR STUDIES.
FOLLOW-UP INTERVALS VARIED
ACROSS STUDIES.
THE OBSERVATIONAL STUDIES WERE
SOMEWHAT CONFOUNDED.
THE FINDINGS OBSERVED FOR FEVER
AND MEDICALLY ATTENDED WHEEZING
REALLY ONLY PERTAINED TO ONE
STUDY DURING A SINGLE SEASON.
IT'S DIFFICULT TO JUDGE ANY RISK
OF SERIOUS ADVERSE EVENTS FROM
THESE TRIALS.
AND IT'S DIFFICULT TO
DISTINGUISH IF A TEMPORAL
ASSOCIATION BETWEEN FLU VACCINE
AND ADVERSE EVENT IS
COINCIDENTAL OR CAUSAL.
SOME CAUTION WHICH REVIEW WAS
LIMITED TO TRIVALENT INFLUENZA
VACCINES THAT WERE GIVEN,
ACCORDING TO CURRENT IND
INDICATIONS AND IT'S REALLY DOES
NOT INCLUDE ANY DATA ON THE NEW
QUADRIVALENT PRODUCTS.
IN SUMMARY, WHEN GIVEN
ACCORDING TO THE CURRENT
INDICATIONS, THERE'S NO EVIDENCE
FOR ANY INCREASED RISK OF
SERIOUS ADVERSE EVENTS OR
MEDICALLY ATTENDED WHEEZING
AFTER LAIV VERSUS TIV IN THIS
AGE GROUP.
THERE IS EVIDENCE FOR SOME
TRANSIENT INCREASED RISK OF MILD
FEVER AFTER THE LAIV.
ONE INFLUENZA SEASON.
THANK YOU.
ANY QUESTIONS OR SHALL WE MOVE
ON TO DR. GROHSKOPF?
ANY QUESTIONS?
HEARING NONE, DR. GROHSKOPF.
R
.
>> ALL RIGHT.
HELLO AGAIN.
OKAY, WITH THAT TO SET THE STAGE
TO HOPEFULLY SORT OF ILLUSTRATE
THAT THE SAFETY EVALUATION IS A
LITTLE BIT ON THE COMPLICATED
SIDE AT LEAST FELT THAT WAY TO
US I THINK RELATIVE TO EFFICACY,
WE CAN DESCRIBE WHAT WE DID AS
FAR AS G.R.A.D.E. FOR THE
SAFETY.
SO WHEN WE DO THE G.R.A.D.E.
EVALUATION, DR. WALTER LAID OUT
THE CHARACTERISTICS OF
INDIVIDUAL PAPERS AND STUDIES.
WHAT WE'RE GOING TO BE DEALING
WITH NEXT IS POOLING OF DATA
FROM THOSE STUDIES.
AS YOU'VE SEEN IT'S NOT ALWAYS
EASY TO DO THAT.
BECAUSE OF THE WAY DEFINITIONS
AND PROCEDURES VARY ACROSS
STUDIES.
SO WE HAVE MADE AN EFFORT TO
PULL OUT SOME INFORMATION THAT
IS HOPEFULLY CLINICALLY
MEANINGFUL.
BUT AT THE SAME TIME IS NOT
OVERWHELMINGLY COMPLICATED.
AND I'M ANTICIPATING WE WILL GET
SOME ASSUMPTIONS ON THIS AND
THINGS THAT COULD BE DONE EITHER
DIFFERENTLY OR WITH SOME
DIFFERENT THOUGHTS.
JUST A COUPLE OF COMMENTS THAT
WILL APPLY MORE OR LESS TO THE
WHOLE PRESENTATION, WHICH WILL
BE SOMEWHAT BRIEFER IN OVERVIEW.
FEVER, MEDICALLY ATTENDED
WHEEZING AND SERIOUS ADVERSE
EVENTS.
FOCUSING EXCLUSIVELY ON THE
YOUNGER CHILDREN, 2-8-YEAR-OLD
AGE RANGE.
WE MADE A DECISION IN DOING THIS
IN OUR GROUP TO EXCLUDE THE
OBSERVATIONAL STUDIES.
WE'VE HAD THE CHANCE TO DISCUSS
AND PRESENT INFORMATION ON THEM,
BUT THERE IS SOME PARTICULAR FOR
THE SAFETY EVALUATION, AN
UNDERLYING CONCERN THAT
DIFFERENCES IN THE UNDERLYING
HEALTH STATUS OF THE TWO
POPULATIONS, THE ONE THAT
RECEIVES THE LIVE ATTENUATED
VERSUS THE INACTIVATED VACCINE
MAY AFFECT THE RESULTS AND
E TERPRETATION OF SAFETY
FOCUS EXCLUSIVELY ON THE
RANDOMIZED TRIALS.
SO WE'RE GOING TO JUST DISCUSS
INFORMATION FOR CHILDREN EIGHT
YEARS, 2-8 YEARS.
THE FIRST SET OF SLIDES, FOUR OF
THEM RELATE TO MEDICALLY
ATTENDED WHEEZING AND THE DATA
ALL COME FROM THE BELSHI STUDY.
BELSHI 2007.
THE REASON FOR THIS IS THAT WE
WERE ABLE TO GET A FAIRLY
CONSISTENT DEFINITION ACROSS
SEVERAL DIFFERENT CATEGORIES OF
CHILDREN. IN THE STUDY.
WE WERE ABLE TO GET INFORMATION
LIMITED TO CHILDREN 24-59 MONTHS
OF AGE WHICH WE THOUGHT WAS
IMPORTANT BECAUSE THERE'S BEEN
SOME CONCERN ABOUT THE YOUNGER
KIDS AND THE OCCURRENCE OF
WHEEZING IN THE YOUNGER
POPULATIONS WHO AREN'T ASSUMED,
AREN'T APPROVED, WELL SORRY, NOT
WERE INCLUDED FOR IVE LAIV.
EXAMPLE IN THE ASHKANAZI PAPER.
THE FIRST SLIDE ONE OF THE
THINGS ABOUT ASHKANAZI, THE
BELSHI STUDY IS THAT THE
CHILDREN IN THE STUDY COULD
EITHER HAVE RECEIVED ONE OR TWO
DOSES OF INFLUENZA VACCINE.
SOME WERE VACCINE NAIVE AND GOT
TWO.
THE CHILDREN A WHO WEREN'T
VACCINE NAIVE GOT ONE.
AND THE DATA REPORTED ALONG THE
LINES OF AFTER DOSE ONE, AFTERD.
AND SO WE WERE ABLE TO BREAK
THIS OUT IN SEVERAL WAYS.
JUST AS IT IS IN THE PAPER.
SO FOR THIS SLIDE, THIS IS DATA
FOLLOWING DOSE ONE WITHOUT
REGARD TO PREVIOUS VACCINATIONS.
SOME OF THESE CHILDREN WOULD
HAVE BEEN VACCINE NAIVE, SOME
NOT.
FOLLOW-UP IS FOR DAY ZERO TO 42.
AND THIS IS DATA LIMITED TO
CHILDREN AGE 24-59 MONTHS.
SO THEY'RE ALL WITHIN THE
INDICATED AGE POPULATION FOR
LAIV.
CONSIDERING THE CHARACTERISTICS
OF THE ALL THE CHARACTERISTICS
THAT FALL UNDER RISK OF BIAS AND
INDIRECTNESS, WE DECIDED THAT
THE, THERE WAS NOT A SERIOUS
RISK OF BIAS OR INDIRECTNESS
CONSIDERING ALL THAT
INFORMATION.
WE DID, HOWEVER, DOWNGRADE ON
IMPRECISION, BECAUSE WE HAVE A
FAIRLY WIDE CONFIDENCE INTERVAL
THAT STRADDLES 1.0.
OVERALL THERE WAS NOT IN THIS
PARTICULAR SLICE OF THE DATA, A
SIGNIFICANT DIFFERENCE IN THE
RISK OF WHEEZING BETWEEN THE TWO
VACCINES.
AND WE ASSESSED THIS AS TYPE 2
OR MODERATE QUALITY OF EVIDENCE.
LOOKING INSTEAD TO SAME
INFORMATION SORT OF SAME
FRAMEWORK, 24-MONTHS,
FOLLOW-UP 0-42 DAYS.
ALSO INFORMATION FOLLOWING THE
FIRST DOSE.
HOWEVER ON THESE ARE THE
CHILDREN WHO WERE NOT PREVIOUSLY
VACCINATED, THESE WERE ALL
CHILDREN WHO WOULD GO ON LATER
TO GET A SECOND DOSE, BUT
VACCINE NAIVE AT THE TIME OF THE
FIRST DOSE IN THIS CASE WE
DOWNGRADED IMLARLY FOR
IMPRECISION.
WE HAVE THE POINTS ESTIMATE OF
RISK DOES FALL A LITTLE CLOSER
ON THE SIDE OF FAVORING THE IT
SHOULD SAY IIV RATHER THAN
CONTROL.
ON THAT FIGURE.
HOWEVER, THE CONFIDENCE INTERVAL
IS FAIRLY BROAD, AND STRADDLES
ACTUALLY REPRESENTING
NO SIGNIFICANT DIFFERENCE
BETWEEN TWO VACCINES.
WE DID DOWNGRADE FOR
IMPRECISION.
SO WE HAVE MODERATE QUALITY OR
TYPE 2 EVIDENCE HERE.
THE NEXT SLIDE, THIS
FOLLOWING DOSE ONE, BUT THE
CHILDREN IN THIS PARTICULAR
SECTION HAVE B
VACCINATED.
SO THESE ARE NOT VACCINE-NAIVE
CHILDREN.
POINT ESTIMATE FALLS MORE ON THE
SIDE FAVORING LAIV.
WHICH WE MIGHT ANTICIPATE
BECAUSE IT'S NOT, THEY'RE NOT
VACCINE-NAIVE.
STILL WE HAVE A BROAD CONFIDENCE
INTERVAL.
WHICH STRADDLES 1.
SO WE HAVE AGAIN ALSO A FAIRLY
BROAD CONFIDENCE INTERVAL,
DOWNGRADING FOR
OVERALL QUALITY OF EVIDENCE,
MODERATE.
AND LASTLY, AMONG THE CHILDREN
WHO WERE VACCINE-NAIVE FOLLOWING
DOSE 2, POINT ESTIMATE IS
WELL OVER INTO THE SIDE FAVORING
LAIV.
IT DOES CROSS ONE JUST BARELY
WITH AN UPPER BOUND OF 1.06.
WE WOULD STILL CALL THIS ASIGNI
THE TWO VACCINES.
WE ALSO DOW
IMPRECISION HERE. SERIOUS CONCE
IMPRECISION, WE GET AN OVERALL
QUALITY OF AGAIN TYPE 2,
MODERATE.
MOVING AWAY FROM WHEEZING, TO
FEVER, AGAIN WE THOUGHT THIS
WOULD BE SIMPLE.
BUT IT WASN'T.
AND WE HAD A PRETTY GOOD
EXPLANATION OF WHY THAT IS.
IDEALLY, WE WOULD LOOK TO POOL
DATA FROM MULTIPLE STUDIES WHERE
WE CAN, WE GET BIGGER NUMBERS.
HOWEVER, IT WAS A LITTLE BIT
TRICKY TO FIGURE OUT THE BEST
WAY TO DO THAT IN THIS
PARTICULAR CIRCUMSTANCE.
THE DEFINITIONS OF FEVER DID
VARY ACROSS STUDIES AND THEY
WERE REPORTED OUT IN DIFFERENT
WAYS.
IN THIS PARTICULAR TABLE, WHAT
WE HAVE A FEVER DEFINED BY
GREATER THAN OR EQUAL TO 38.6
DEGREES CELSIUS, WHICH IS
ROUGHLY 101.5.
FOR THE ASHKANAZI PAPER.
AND FOR BELSHI, GREATER THAN OR
EQUAL TO 38.9, WHICH IS ROUGHLY
102 DEGREES FAHRENHEIT FOR THE
BELSHI PAPER.
AND WE HAVE POOLED THOSE.
AND THIS IS FOLLOW-UP FOR DAY
0-10.
SO IT'S A LITTLE LONGER
FOLLOW-UP THAN WHAT DR. WALTER
REPORTED WHEN HE DISCUSSED SOME
OF THE EARLIER FEVER OUTCOMES
FOR EXAMPLE, THE SLIGHTLY
INCREASED RISK OF FEVER IN
DURING ONE SEASON FOR TWO DAYS
POST-VACCINATION.
WE HAVE A SLIGHTLY LONGER
INTERVAL HERE.
AND AGAIN, THE TEMPERATURES
THRESHOLDS DO DIFFER SLIGHTLY.
FOR THIS, WE HAVE AGAIN, WE HAVE
A SLIGHTLY BROAD CONFIDENCE
INTERVAL, THE G.R.A.D.E.
HANDBOOK RECOMMENDS CONSIDERING
DOWNGRADING FOR IMPRECISION WHEN
THE LOWER BOUND CROSSES 0.75.
THIS GOES TO 0.73.
SO WE DID CALL THIS, WE DID MAKE
A CALL FOR DOWNGRADING FOR
IMPRECISION IN THIS PARTICULAR
ANALYSIS.
AND WE'RE CALLING THIS TYPE 2
MODERATE.
BUT NO SIGNIFICANT DIFFERENCE
BETWEEN THE TWO VACCINES.
AT LEAST ACCORDING TO THIS
ANALYSIS.
THE LAST DATA SLIDE HERE, I HAVE
IS SAEs, FOCUSING ON RELATED
SAEs, BECAUSE WE WERE TRYING TO
GET SOMETHING A BIT MORE
SPECIFIC.
SO THESE AGAIN, RELATED SAEs
WOULD BE SERIOUS ADVERSE EVENTS
THAT IN THE JUDGMENT OF THE
INVESTIGATOR WERE PROBABLY
RELATED TO VACCINATION.
YOU SAW SOME OF THE
CHARACTERISTICS OF SOME OF THESE
SAEs IN DR. WALTER'S SLIDE.
THE RELATED ONES IN PARTICULAR,
MOST RELATED TO RESPIRATORY
SYMPTOMS.
AND BECAUSE THOSE WERE
RELATIVELY UNCOMMON, EVEN LESS
COMMON THAN THE TOTAL SAEs, WE
DON'T HAVE THE DATA ARE SOMEWHAT
SPARSE.
WE HAVE A PARTICULARLY BROAD
CONFIDENCE INTERVAL HERE.
DID THEY DOWNGRADE FOR
IMPRECISION?
WE HAVE DATA THAT CROSSES 1.
WE HAVE NOT ASSIGNED A VALUE TO
THIS PARTICULAR OUTCOME BECAUSE
IT'S NOT A COMPLETELY CERTAIN
HOW MEANINGFUL IT IS.
WE PROBABLY WILL HAVE MORE
DISCUSSION ABOUT THAT WITHIN
WORK GROUP.
ALTHOUGH THERE WASN'T READILY
APPARENT CONSENSUS FROM THE WORK
GROUP ABOUT HOW THEY WOULD WANT
TO VALUE IT.
WE DID FEEL IT WAS IMPORTANT TO
LOOK AT, BECAUSE SOME OF THE
MORE RARE AND SERIOUS OUTCOMES
ARE SO RARE WE COULD NOT GET AN
ACCURATE ASSESSMENT AND WE'RE
HOPING TO USE THIS AS SOME SORT
OF PROXY TO SEE IF WE COULD FIND
ANYTHING.
BUT WE DID NOT.
OVERALL QUALITY OF EVIDENCE HERE
WAS JUDGED TO BE TYPE 2 OR
MODERATE.
SO TO SUMMARIZE FOR THESE THREE
OUTCOMES, CRITICAL MEDICALLY
ATTENDED WHEEZING, NO
DIFFERENCE.
TYPE TWO OR MODERATE.
FEVER, IMPORTANT VALUES AN
OUTCOME, TYPE 2 OR MODERATE.
RELATED SAEs, NO DIFFERENCE,
TYPE 2 OR MODERATE.
MOVING ON TO LIMITATIONS, DR.
WALTER A I DRESSED SOME OF THIS
IN HIS TALK.
BUT I'LL REITERATE IT BECAUSE I
THINK IT BEARS REPEATING.
THE DEFINITIONS OF THE OUTCOMES
OF INTEREST ARE NOT STANDARDIZED
ACROSS THE STUDIES.
THERE'S DIFFERENCES THAT MAKE IT
YOU WILL FAIRLY TRICKY TO
DETERMINE HOW WE MIGHT POOL DATA
IN A WAY THAT'S BOTH MEANINGFUL
AND WILL ALLOW US TO GET A
BETTER ASSESSMENT WITH BETTER
POWER FROM BETTER NUMBERS.
STUDIES ALSO HERE ARE NOT
ADEQUATELY POWERED TO DETECT
DIFFERENCES POTENTIALLY
DIFFERENCES IN SOME OF THE
EVENTS WE'VE LOOKED AT.
BUT ALSO DIFFERENCES IN SOME OF
THE RARE BUT SERIOUS AND
IMPORTANT OUTCOMES.
FOR EXAMPLE GILLEN BAR,
ANAPHYLAXIS, FEBRILE SEIZURE,
THESE WOULD BE THINGS BETTER
EVALUATED IN LARGER
POPULATION-BASED STUDIES.
WHICH WE HAVEN'T EVALUATED HERE.
AND ALL OF THE DATA PERTAIN TO
TRIVALENT VACCINES, BECAUSE
THOSE WERE WHAT WAS AVAILABLE
WHEN THESE THINGS WERE DONE.
WITH THAT, I'D LIKE TO THANK
EVERYBODY THAT ASSISTED WITH THE
EVALUATION.
WE APPRECIATED THE ABILITY TO
HAVE IMMUNIZATION SAFETY OFFICE
AND CISA INPUT ON THIS AS WE
FORMULATED THE APPROACH TO
THINGS.
AND ALSO LIKE TO THANK EVERYONE
ELSE ON THIS SLIDE.
THANKS, I'D BE HAPPY TO TAKE ANY
QUESTIONS.
THANKS VERY MUCH FOR A CLEAR
AND SUCCINCT PRESENTATION THAT
PULL IT IS ALL TOGETHER.
ARE THERE QUESTIONS FROM THE
COMMITTEE OR LIAISONS?
DR. KARRON?
THANKS VERY MUCH.
I JUST WILL A QUESTION THERE WAS
ONE SLIDE I THINK IT WAS MAYBE
YOUR FIFTH SLIDE.
IT WAS FIRST DOSE IN NAIVE
CHILDREN WHERE CLEARLY THE
SSED 1.
BUT IT LOOKED LIKE THERE WAS
A TREND.
AND I SEEM TO REMEMBER THAT IN
OUR WORK GROUP WE HAD ALSO
LOOKED TO THESE, THIS IS 0-42
DAYS.
I THINK WE LOOKED AT A SHORTER
INTERVAL THAT WAS MORE RELATED
TO THE PERIOD OF LAIV
REPRESENTLY INDICATIOREPRESENT
REPRESENTLY REPRESENTLY
REPLICATION.
I WAS WONDERING IF YOU COULD
REMIND US HOW THAT WAS RELATIVE
TO THIS?
>> THERE'S A SLIDE NOT INCLUDED
HERE, BECAUSE STRICTLY SPEAKING,
IT DIDN'T MEET THE CRITERIA FOR
MEDICALLY ATTENDED WHEEZING.
BUT THE ASHKANAZI PAPER REPORTED
FOR DAY 0-11 THEY DID REPORT
WHEEZING AS AN OUTCOME.
IT WAS REPORTED ON DIARY CARDS
FROM THE PARENTS, SO THERE WAS
NO PRACTITIONER VERIFICATION.
THAT THAT HAD OCCURRED.
AND WE DID LOOK AT THAT IN WORK
GROUP.
BUT WE DIDN'T INCLUDE IT HERE.
THE TAKE-HOME POINT FROM THAT IS
THAT THERE WAS NO DIFFERENCE
BETWEEN THE TWO.
WE WERE ABLE TO GET SOME
INFORMATION FROM FDA WITH REGARD
TO EARLIER WHEEZING DURING
EARLIER INTERVALS FOR CHILDREN
24 MONTHS AND UP.
WHICH BASICALLY GOING OUT DURING
THE FIRST TEN DAYS FOLLOWING
VACCINATION TO SHOW NO
DIFFERENCE.
IN THE RATES OF WHEEZING.
AND THOSE DATA CAME FROM THE
BELSHI STUDY.
I WILL TRY TO GET THAT OUT TO
FOLKS FOLLOWING THE MEETING.
ANY OTHER COMMENTS?
>> IF WE CAN THEN, I GUESS ASK
IS IT DR. COELINGH?
>> THANK YOU TO THE COMMITTEE
AND GOOD MORNING.
I HAVE A VERY BRIEF SUPPLY
UPDATE THIS MORNING.
ON LAIV.
BEFORE I DO THAT, I WOULD LIKE
TO JUST SHOW ONE SLIDE THAT OUR
PRESENT IN YOUR
AND THI IN RESPONSE TO THE
QUESTION THAT WAS RAISED
EARLIER.
ABOUT THE RELATIVE EFFICACY OF
LAIV IN VACCINE-NAIVE CHILDREN
OR CHILDREN WHO HAVE BEEN
VACCINATED PREVIOUSLY OR HAVE
EXPERIENCED INFLUENZA.
AND THIS, THIS SLIDE SHOWS THERE
WERE FOUR PLACEBO-CONTROLLED
STUDIES DONE DURING THE CLINICAL
DEVELOPMENT OF LAIV.
FOUR OF THOSE STUDIES WERE
TWO-SEASON STUDIES.
SO THOSE STUDIES ARE SHOWN ON
THIS SLIDE.
THE FIRST EFFICACY AND THIS IS
ABSOLUTE EFFICACY COMPARED TO
PLACEBO.
SO THE FIRST STUDY THAT WE'RE
LOOKING AT IS THE BELSHI STUDY.
FIRST SEASON ABSOLUTE EFFICACY
OF 93%.
SECOND SEASON, AFTER
REVACCINATION, WAS 100%.
THE VESICARI STUDY, 85% FIRST
YEAR, 89% SECOND YEAR.
BRACCO, 74% EFFICACY IN BOTH
YEARS.
OF THE REVACCINATION AND THEN
THE TAMM STUDY, 73% EFFICACY THE
FIRST YEAR, 84% THE SECOND YEAR.
AND THESE STUDIES WERE PERFORMED
IN CHILDREN THAT ARE NOT IN THE
EXACT AGE GROUP THAT WE'RE
TALKING ABOUT TODAY, 2-8 YEARS.
THESE CHILDREN WERE GENERALLY
YOUNGER.
THEN THE OTHER PIECE OF
INFORMATION THAT'S RELEVANT TO
THAT PARTICULAR QUESTION IS, IN
THE LARGE BELSHI STUDY THAT WAS
CONDUCTED THAT THE HEAD-TO-HEAD
TRIAL OF LAIV VERSUS TIV, AND IN
THAT STUDY, HE ACTUALLY DID
ANALYZE CHILDREN WHO HAD BEEN
VACCINATED PREVIOUSLY WITH IIV.
AND COMPARED THAT TO CHILDREN
WHO WEREN'T PREVIOUSLY
VACCINATED WITH IIV.
THE EFFICACY WAS SIMILAR,
WHETHER OR NOT THEY WERE
PREVIOUSLY VACCINATED.
IF THEY WERE PREVIOUSLY
VACCINATED, THE EFFICACY WAS 51%
FEWER CASES WITH LAIV COMPARED
TO IIV.
IN THE REVERSE SITUATION, WHEN
THEY WERE NOT PREVIOUSLY
VACCINATED, IT WAS 57% FEWER
CASES WITH, IN THE LAIV GROUP
COMPARED TO THE IIV GROUP.
SO THAT'S THE INFORMATION
RELATIVE TO THAT, RELEVANT TOUE.
SO I WOULD JUST LIKE TO TURN
THEN TO THIS BRIEF SUPPLY UPDATE
THAT I NEED TO GIVE TODAY.
SO JUST FOR CLARITY, THE
SEASONAL LIVE ATTENUATED
INFLUENZA VACCINE IS APPROVED IN
THE U.S. FOR ELIGIBLE
INDIVIDUALS 2-49 YEARS OF AGE.
IT CONTAINS 6.5 TO 7.5 OF EACH
VACCINE STRAIN PER DOSE.
AND THE QUADRIVALENT WAS
INTRODUCED IN THE UNITED STATES
STARTING IN THE CURRENT 2013-14
SEASON.
IT CONTAINS NO PRESERVATIVES OR
ADJUVENTS, STORED REFRIGERATED
AND ADMINISTERED AS A NASAL
SPRAY, 75 MILLION DOSES OF THE
LAIV DISTRIBUTED IN THE UNITED
STATES SINCE LICENSURE IN 2003.
OKAY, THIS SLIDE SHOWS THE TOTAL
DOSES OF LAIV PRODUCED BY
SEASON.
STARTING IN 2003, WHEN WE WERE
LICENSED.
AND GOING UP TO THE CURRENT
TIME.
IN THE EARLY STAGE, IN THE EARLY
YEARS FOLLOWING LICENSURE, THE
PRODUCTION WAS VERY MODEST AS
YOU CAN SEE.
BUT IT'S INCREASED AFTER AROUND
2008, WHEN THE PRODUCT WAS
LICENSED DOWN TO AGE TWO.
WHEN IT NO LONG HER TO BE STORED
FROZEN IN A FREEZER.
AND WHEN ACIP RECOMMENDED
ROUTINE ANNUAL VACCINATION OF
ALL CHILDREN.
SO WE'VE SEEN THE INCREASE, I
ALSO WANT TO POINT OUT TO YOU
THAT LARGE SPIKE IN 2009 IS THE
COMBINATION OF THE PANDEMIC AND
SEASONAL VACCINES.
AND AS YOU CAN SEE, THE GRADUAL
INCREASE IN PRODUCTION FOR THE
2013-14 SEASON.
WE PRODUCED 22 MILLION DOSES OF
WHICH ABOUT 13 MILLION HAVE BEEN
DISTRIBUTED IN THE UNITED
STATES.
WE'RE PLANNING TO PRODUCE ABOUT
24 MILLION DOSES IN THE UPCOMING
2014-15 SEASON, UNLESS
ADDITIONAL INFORMATION JUSTIFIES
EITHER INCREASING OR DECREASING
THAT NUMBER.
SO I ALSO WANTED TO SHOW THIS
INFORMATION, LAIV HAS BEEN
INCREASINGLY ADMINISTERED TO
U.S. CHILDREN, 2-17 YEARS OF
AGE.
AND THE DATA ON THIS SLIDE IS
FROM LARGE NATIONAL INSURANCE
CLAIMS DATABASE.
AND IT EXCLUDES THE PANDEMIC
DOSES.
SO THIS SHOWS THE PERCENTAGE OF
CLAIMS FILED BY PRIVATELY
INSURED CHILDREN, FOR INFLUENZA
VACCINE BY VACCINE TYPE, AND BY
YEAR.
SO THIS SLIDE SHOWS THE ACTUAL
USAGE STARTING IN 2007-2008 AND
GOING UP TO 2011-12, THE MOST
RECENT DATA THAT WE HAVE.
AND IT SHOWS THE PROPORTIONAL
USE OF IIV IN MULTIDOSE VIALS,
WHICH IS SHOWN IN THE WHITE
BARS.
THE STIPPLE BARS SHOW THE USE OF
THE PREFILLED PRESERVATIVE-FREE
SYRINGES OF IIV.
AND THE SOLID BLUE BARS SHOW THE
PERCENTAGE OF CLAIMS THAT WERE
FILED FOR LIVE ATTENUATED
INFLUENZA VACCINE.
OVER THIS TIME PERIOD, THE USE
OF MULTIDOSE
PRESERVATIVE-CONTAINING VIALS
DECREASED FROM 69% IN 2007-2008,
TO 35% OVER IN 2011-2012.
IN CONTRAST, THE USE OF THE
PREFILLED SYRINGES OF IIV HAS
INCREASED IN THIS PERIOD FROM
19% TO 25%.
AND YOU CAN SEE THE USE OF LAIV
HAS INCREASED FROM 12% TO 40% IN
2011-2012.
THE INFORMATION FOR THE CURRENT
SEASON ARE JUST STARTING TO COME
IN.
IT LOOKS LIKE THESE TRENDS ARE
CONTINUING AND THAT FOR THE
PERCENTAGE OF LAIV IS ABOUT 44%.
SO I'VE SHOWN YOU THE INCREASING
USE OF LAIV AND I'VE ALSO SHOWN
YOU HOW WE HAVE INCREASED OUR
PRODUCTION IN ORDER TO MEET THE
DEMAND FOR INCREASED NUMBER OF
DOSES.
SO IN THE NEXT SLIDE, I WOULD
LIKE TO SHOW YOU OUR CAPACITY
FOR RESPONDING TO A POTENTIALLY
GREATER DEMAND FOR LAIV IN THE
YOU SO THIS SHOWS THE CURRENT
AND PROJECTED LAIV MANUFACTURING
CAPACITY, COMPARED TO POTENTIAL
DEMAND.
AND THE DATA ON THESE, ON THIS
SLIDE, THE ESTIMATES ASSUME A
50% OVERALL VACCINATION RATE
AMONG U.S. CHILDREN 2-17 YEARS
OF AGE.
USING ANY VACCINE TYPES.
SO THAT'S THE CURRENT COVERAGE
THAT WE HAVE APPROXIMATELY.
AND LOOKING THEN, AT THE 2013
CURRENT SEASON, YOU SEE A DEMAND
FOR LAIV, OF 16 MILLION DOSES,
13 MILLION IN THE U.S. AND THREE
MILLION EX--U.S.
IN THE HORIZONTAL LINE, YOU SEE
THE MANUFACTURING CAPACITY THAT
WE HAVE FOR MAKING THIS.
AND YOU NOTE, THAT THERE IS A
LARGE AMOUNT OF UNUSED
MANUFACTURING CAPACITY.
THAT WE'RE NOT USING RIGHT NOW.
BECAUSE WE HAVE A CAPACITY TO
MAKE 30 MILLION DOSES.
BUT WE'VE ONLY HAD TO MAKE 16
MILLION DOSES.
IF YOU LOOK GOING FORWARD TO THE
2014-15 SEASON, AND YOU, IF YOU
TOOK A THEORETICAL DEMAND THAT
70% OF ALL CHILDREN THAT ARE
ELIGIBLE FOR LAIV WOULD GET IT,
SO YOU GO FROM THE CURRENT
SITUATION, WHERE THERE'S A 40%
MARKET SHARE, AND IF YOU WOULD
SAY, WHAT WOULD HAPPEN IF YOU
MOVED THAT TO A 70% MARKET
SHARE, AND IN EITHER 2-8, OR
2-17, YOU WOULD COME UP WITH
THIS KIND OF A DEMAND, WHICH
AGAIN, IS MET ADEQUATELY BY OUR
MANUFACTURING CAPACITY.
IF YOU MOVE ON, YOU CAN SEE THAT
WE WOULD PREDICT THAT IN
2015-16, WE'LL AGAIN BE INTO A
SITUATION OF EXCESS
MANUFACTURING CAPACITY.
BECAUSE OUR MANUFACTURING
CAPACITY IS GOING TO INCREASE TO
35 MILLION DOSES THEN.
AND I WOULD ADD THAT IF YOU
ASSUME THAT GOING FORWARD IN THE
UNITED STATES, IF WE MEET THE
GOALS OF THE HEALTHY PEOPLE
2020, WHERE YOU ACTUALLY REACH
CLOSE TO A 70% COVERAGE RATE, WE
WILL BE ABLE TO MAKE THAT.
EVEN WITH THESE HIGHER MARKET
SHARES.
BECAUSE WE PLAN AS NOTED IN THE
FOOTNOTE, THAT WE WILL BE GOING
TO 47 MILLION DOSES.
FOR THE 16-17 INFLUENZA SEASON.
SO SUMMING UP, OUR CURRENT AND
PROJECTED MANUFACTURING CAPACITY
FOR LAIV IS SUFFICIENT FOR
ELIGIBLE U.S. CHILDREN.
AT BOTH CURRENT AND HIGHER
FUTURE LAIV USE.
AT CURRENT AND HIGHER FUTURE
VACCINATION COVERAGE LEVELS.
AND TO MEET BOTH U.S. AND
EX-U.S. DEMAND.
ADDITIONAL INCREASES IN U.S.
DEMAND COULD BE MET BY FURTHER
INCREASES IN MANUFACTURING
CAPACITY.
THANK YOU AND I'LL TAKE ANY
QUESTIONS THAT YOU MIGHT HAVE.
DR. KARRON?
>> THANK YOU, KATHY.
I WANT TO UNDERSTAND THE
RELATIONSHIP BETWEEN CAPACITY
AND SUPPLY IN ANY GIVEN YEAR.
AND ALSO, HOW THOSE RELATE
POTENTIALLY TO OUR FUTURE POLICY
DECISIONS.
AND WHAT I MEAN BY THAT IS, YOU
KNOW, THERE MIGHT BE A SITUATION
WHERE WE HAVE A CLEAR
PREFERENTIAL RECOMMENDATION FOR
LAIV IN A CERTAIN AGE GROUP.
THERE MIGHT BE A SITUATION WHERE
WE TALK ABOUT CONSIDERATION OF
USE OF LAIV IN VARIOUS AGE
GROUPS.
HOW DOES THAT AFFECT
YEAR-TO-YEAR SUPPLY?
.
THAT'S A BIG QUESTION, RUTH.
I HOPE I CAN ANSWER IT.
BUT I THINK THAT THIS SLIDE SAYS
A LOT.
SO THIS, THIS SHOWS THE CURRENT
SITUATION.
IT'S HARD TO PREDICT WHAT KIND
OF, WHAT KIND OF DEMAND WOULD BE
TRIGGERED BY A PREFERENCE IN THE
UNITED STATES.
WE JUST CHOSE TO LOOK AT 70%, IF
YOU LOOK HISTORICALLY AT THE
ACIP RECOMMENDATIONS, WHEN THE
ACIP MAKES A RECOMMENDATION FOR
A NEW VACCINE, IT DOESN'T
TRIGGER THIS AUTOMATIC MOVEMENT
TOWARD THAT FOLLOWING THAT
RECOMMENDATION.
IT ALWAYS TAKES A FEW YEARS FOR
THAT TO GO INTO EFFECT.
SO YOU'RE KIND OF GETTING WHAT
MIGHT HAPPEN.
BUT WE THOUGHT THAT MODELING
THIS OVER THE NEXT FEW YEARS.
WOULD PROVIDE SOME REASSURANCE
THAT THE CAPACITY IS ADEQUATE.
AND THAT WE JUST HAVE TO USE IT.
BECAUSE AS I WOULD POINT OUT,
WE'RE ONLY USING HALF OF OUR
CAPACITY NOW THIS YEAR.
RIGHT NOW.
FOR THE CURRENT SEASON.
AND THAT IS EXPANDING TO 47
MILLION DOSES BY THE 16-17
SEASON, WHICH WOULD BE ADEQUATE
IN OUR ESTIMATION TO COVER
EVERYBODY WHO WOULD BE LIKELY TO
WANT TO GET IT.
SO CAN I JUST HAVE A
FOLLOW-UP TO THAT?
FLU VACCINE IS THE MOST
PERISHABLE VACCINE OF ALL,
RIGHT?
IT COMES AND IT GOES.
AND OBVIOUSLY A COMPANY HAS TO
WEIGH DEMAND AGAINST CAPACITY
YOU MIGHT NOT PRODUCE ALL
THAT YOU CAN PRODUCTION.
IF YOU CAN'T USE IT.
AND SO I GUESS, SO I GUESS WHAT
I WAS ARRIVING AT IS WHERE IN
TERMS, NOT JUST IN TERMS OF
ABSOLUTE CAPACITY TO PRODUCE,
BUT AS I GUESS TRYING TO
UNDERSTAND MORE ABOUT THE
FORECASTING PROCESS, WHICH IS
PROBABLY VERY, TOO COMPLEX EVEN
TO DISCUSS, BUT DEPENDING ON
POLICY RECOMMENDATIONS.
HOW -- RUTH, POLICY
RECOMMENDATIONS ARE TAKEN INTO
ACCOUNT.
LIKE I SAID, THEY, IT'S NOT LIKE
AN INSTANT TURNING ON THE HOT
WATER AND YOU KNOW, AND PEOPLE
FOLLOW RECOMMENDATIONS RIGHT
AWAY.
AS FAR AS FORECASTING, I
CERTAINLY AM NOT INVOLVED IN
THAT.
SO IT'S VERY, A LITTLE BIT
DIFFICULT FOR ME TO ANSWER THAT
QUESTION.
CLEARLY, POLICY PLAYS A HUGE
ROLE AS YOU WELL KNOW.
IN HOW THE DEMAND FOR VACCINES.
AND IT'S GOING TO BE EVEN MORE
SO GOING FORWARD.
WITH OUR CHANGES IN HEALTH CARE.
>> DR. SAWYER?
I JUST WANTED TO MAKE SURE I
UNDERSTAND THIS SLIDE.
I THINK IT'S BASED ON A 50%
INMUMIZATION COVERAGE RATE
OVERALL, IS THAT CORRECT?
>> THAT'S CORRECT.
IS THERE A COVERAGE RATE AT
WHICH YOU WOULD NO LONGER BE
ABLE TO MEET THE DEMAND?
LET'S SAY WE WERE AT 70%
COVERAGE RATE AND 70% OF THOSE
CHILDREN RECEIVED LAIV?
WE DID MODEL THAT JUST FOR
SIMPLICITY AND TO KEEP THE
NUMBER OF SLIDES DOWN, I DIDN'T
INCLUDE THAT I JUST WANTED TO
PUT IT ALL ON ONE SLIDE.
BUT IF YOU DO INCREASE THAT UP
TO 70%, AND ALSO LOOK AT A 70%
MARKET SHARE FOR WHERE -- IT'S
ADEQUATE, YES.
>> KATHY STINCHFIELD FROM
NAPNAP.
I WOULD LIKE YOU TO COMMENT ON
THE TRUE ELIGIBLE CHILDREN.
AS A WORK GROUP NUMBER WE TALKED
A LOT ABOUT THOSE KIDS FOR WHOM
FLU VACCINE IS CONTRAINDICATED.
WHAT ARE THE TRUE CONT
CONTRAINDICATIONS VERSUS THAT
WHICH WE HAVE IN OUR ACIP
STATEMENT.
HEALTHY CHILDREN AND I THINK
DEFINING IT CLEARLY DOES IMPACT
WHO YOU'RE GOING IT TO AND YOUR
SUPPLY.
IF YOU COULD TALK ABOUT TRUE
CONTRAINDICATIONS.
WELL, I THINK THE DIFFICULTY
IS, THAT WHAT IS A TRUE
CONTRAINDICATION.
SO I THINK YOU MEAN THE LEGAL
REGULATORY CONTRAINDICATION, AS
GIVEN BY THE FDA.
SO THE CONTRAINDICATIONS IN OUR
LABEL, WHICH IS ISSUED BY THE
FDA, ARE FOR YOU KNOW, CHILDREN
WHO ARE ON ASPIRIN THERAPY.
AND ANYONE WHO IS ALLERGIC TO A
PREVIOUS DOSE OF VACCINE.
SO IT COULD BE ALLERGIC TO THE
VACCINE ITSELF OR ANY EXCIPIENT,
FOR EXAMPLE, EGGS.
SO I CAN'T REALLY COMMENT, I'M
IN AN AWKWARD POSITION.
YOU RECOGNIZE TO TALK ABOUT TRUE
CONTRAINDICATIONS VERSUS WHAT
ACIP RECOMMENDS.
BECAUSE OF COURSE WE, WE HAVE TO
TAKE THE YOU KNOW THE JUDGMENT
OF THE COMMITTEE.
THAT'S WHAT THIS COMMITTEE DOES.
I WANT TO FOLLOW UP.
I DIDN'T MEAN TO PUT YOU IN AN
AWKWARD POSITION.
I APOLOGIZE IF I DID I THINK THE
POINT IS TO HIGHLIGHT THE
DIFFERENCE BETWEEN THOSE TWO
TRUE CONTRAINDICATIONS, AND
HEALTHY 2-YEAR-OLDS AND OVER IS
QUITE A BIG DIFFERENCE.
AND WE NEED TO TALK MORE ABOUT
THAT.
>> DR. KARRON?
JUST TO SORT OF FOLLOW UP ON
AND I THINK ACTUALLY WE SHOULD
JUST PROBABLY ALSO SAY IN TERMS
OF LABELS, TRUE
CONTRAINDICATIONS,
IMMUNOCOMPROMISED, THOSE
CATEGORIES ALONG WITH ASPIRIN
THERAPY AND ALLERGIC CHILDREN.
I WAS WONDERING IF OUR NASI
COLLEAGUES OR I DON'T KNOW IF
THERE'S ANYONE HERE FROM THE UK.
PLACES WHERE LAIV IS BEING USED
IN CHILDREN WITH PREVIOUS
HISTORY OF WHEEZING, WHETHER
THEY HAVE ANY KIND OF REGISTRY
OR DATA COLLECTION TO TELL THEM
ABOUT ADVERSE EVENTS THAT OCCUR
IN THESE POPULATIONS BECAUSE I
KNOW LAIV IS USED DIFFERENTLY IN
SOME OTHER COUNTRIES.
ANY COMMENT FROM CANADA?
NATIONAL ADVISORY COMMITTEE ON
IMMUNIZATION.
DEWEE DO HAVE A VACCINE REGISTRY
JUST AS YOU DO.
A PASSIVE SYSTEM FOR REPORTING.
I'M NOT AWARE OF PARTICULAR
ANALYSIS DONE ON LAIV AND I'M
ALSO NOT AWARE IF THERE'S BEEN
ANY SAFETY SIGNALS BROUGHT UP.
THAT'S BEEN BROUGHT TO OUR
ATTENTION AS FAR AS LAIV.
HOW ABOUT DR. SALISBURY?
>>.
DEVON SALISBURY FROM THE UK.
SO FAR WE'VE ONLY BEEN
VACCINATING 3-YEAR-OLDS AND
4-YEAR-OLDS THIS WINTER.
WE HAVE 40% COVERAGE WITH LAIV
IN THOSE TWO AGE GROUPS.
BUT I'M NOT AWARE, EITHER, OF
ANY SPECIFIC ADVERSE EVENTS
BECAUSE SO FAR WE HAVE BEEN ONLY
USING THEENSED SPECIFIED
INDICATIONS AND
CONTRAINDICATIONS.
SO ANYTHING THAT COMES FROM USE
OUTSIDE OF THE RECOMMENDATIONS,
CERTAINLY HASN'T SURFACED YET.
AND THE OTHER DIFFERENCE IS WE
ARE ONLY USING ONE DOSE IN ALL
OF OUR AGE GROUPS.
WITH LAIV ON THE BASIS THAT THE
INCREMENTAL ADVANTAGE OF THE
SECOND DOSE DOESN'T REALLY SEEM
TO WARRANT ITS USE.
THANK YOU.
>> SORRY, DAVID, JUST A
FOLLOW-UP QUESTION TO THAT.
I THINK IF I UNDERSTAND THE
CONTRA USE OF
FLU-Ns, YOUR EUROPEAN PRODUCT.
IT'S CHILDREN WITH SEVERE
WHEEZING OR ACTIVE WHET
OUTSIDE THE THEY IMMUNIZATION,
LAWOULDN'T EXCLUDE CHILDREN
WITH ANY HISTORY OF WHEEZING.
>> IT'S CLOSER TO THE CANADIAN
SITUATION.
YES.
THERE WAS A GENTLEMAN UP AT
THE MICROPHONE?
YES, THANK YOU.
LAST MINOR MEDIMMUNE OPERATION
STRATEGY AND PLANNING.
QUESTION REGARDING FORECASTING
VERSUS PLANNING.
WE DO PLAN TO PRODUCE ADDITIONAL
BULK AND FINISHED GOOD MATERIAL
EVERY SEASON ABOVE AND BEYOND
THE EXPECTED DEMAND.
AND THEN WE HAVE OPTIONS MID
SEASON TO PRODUCE EVEN FURTHER.
>> THANK YOU.
OTHER COMMENTS?
DR. GROHSKOPF?
I THINK WE'RE READY FOR THE
PROPOSED RECOMMENDATIONS.
ALL RIGHT.
THANKS.
SO AS I MENTIONED AT THE OUTSET
OF THE SESSION, AT PRESENT THE
WORK GROUP IS NOT PROPOSING ANY
CHANGES TO THE RECOMMENDATIONS
FOR NEXT SEASON.
WE WILL HAVE AN OPPORTUNITY TO
DISCUSS MORE CHANGES IN JUNE,
SHOULD THERE BE THE NEED TO DO
THAT.
AND THERE ARE SOME TOPICS THAT
CONTINUE TO HAVE SOME ONGOING
DISCUSSION WITHIN THE WORK
GROUP.
WHAT WE WOULD HAVE PLANNED TO DO
TODAY WAS BASICALLY SORT OF
REITERATE THE CORE
RECOMMENDATIONS FOR ANY
VACCINATIONS BEING RECOMMENDED
FOR PERSONS SIX MONTHS AND
OLDER.
WE'VE BEGUN TO DRAFT A POLICY
NOTE FOR THE MMWR FOR THE NEXT
YEAR.
FOR THIS SEASON AFTER TWO YEARS
OF HAVING RECOMMENDATIONS DONE
AS POLICY NOTES.
JUST WITH SHORT PERTINENT
UPDATES, WE DID FOR THE 13-14
SEASON GO BACK TO A FULL FORMAT
MMWRR AND HAVING DONE THAT WE
PLANNED FOR NEXT SEASON, UNLESS
CIRCUMSTANCES CHANGE TO GO BACK
TO THE SMALLER POLICY NOTE
FORMAT.
THAT DOCUMENT HAS BEEN DRAFTED
AND CONSISTS RIGHT NOW ONLY OF
THOSE ITEMS THAT ARE KNOWN OR
ASSUMED THAT THEY'RE NOT LIKELY
TO CHANGE AND THE ACIP MEMBERS
HAVE RECEIVED A KOLPY OF THAT
FOR REVIEW AND COMMENT.
ANY PROPOSED CHANGES WE INTENT
TO HAVE DISCUSSED AND PRESENTED
AT THE JUNE 2014 MEETING.
ANOTHER THING TO NOTE THIS TIME
LAST YEAR WE HAD A LOT OF NEW
PRODUCTS OUT OR ON THE HORIZON
ABOUT TO BE LICENSED.
AS OF THIS POINT IN TIME, WE
HAVE NOT AWARE OF ANY NEW
LICENSURES, THERE MAY BE SOME
BETWEEN NOW AND JUNE.
CURRENTLY IN THE DRAFT POLICY
NOTE, ALL OF THE LICENSED
VACCINES ARE SUMMARIZED IN THE
DRAFT TABLE, WHICH IS
ESSENTIALLY AT THIS POINT
IDENTICAL TO THE CURRENT SEASON
TABLE.
IT WILL BE UPDATED AS NEW
PACKAGE INSERTS ARE OUT AND ALSO
WITH ANY NEW LICENSURES AS THEY
OCCUR.
AND ANY NEW LICENSURES THAT
OCCUR BETWEEN NOW AND JUNE WILL
BE DISCUSSED AT THE NEXT
MEETING.
FOR TODAY WE'RE JUST PROPOSING
REITERATION OF THE CORE
RECOMMENDATIONS FOR VACCINATION
FOR EVERYONE SIX MONTHS AND
OLDER.
NOW JUST ONE LITTLE BRIEF THING.
THE VACCINE STRAIN SELECTION FOR
NEXT SEASON, THE WORLD HEALTH
ORGANIZATION HAS HAD ITS STRAIN
SELECTION MEETING AND IS
RECOMMENDED THE SAME COMPOSITION
FOR THE NORTHERN HEMISPHERE
VACCINE.
FOR 2014-15 AS HAS BEEN USED
THIS SEASON 13-14.
THAT WILL BE DISCUSSED AT THE
FDA VARPAC MEETING THIS WEEK WE
DON'T KNOW WHAT THE STRAINS WILL
BE FOR THE U.S. THIS WEEK, THAT
WILL BE DISCUSSED AT VAERPAC.
THOSE WILL BE RECOMMENDED IN THE
DRAFT WITH SOME PLACE-HOLDERS
UNTIL WE KNOW THAT INFORMATION.
I WANT TO THANK EVERYBODY THAT'S
INVOLVED IN PREPARING ALL OF
THIS, AND IN PARTICULAR I WANT
TO THANK -- WE'VE BEEN WORKING
ON THE G.R.A.D.E. STUFF AND
SPENDING QUITE A BIT OF TIME
TOGETHER.
AND THAT IS ALL I HAVE FOR THIS.
AND ANY QUESTIONS ARE WELCOME,
PLEASE.
THANK YOU, DR. GROHSKOPF.
I SEE A COUPLE OF HANDS UP.
DR. HARRISON.
>> IN TERMS OF PROPOSED CHANGES,
WHAT INFORMATION WILL WE HAVE IN
JUNE THAT WE DON'T HAVE NOW?
WELL FOR ONE THING, AS
MENTIONED, ONE ISSUE WITH REGARD
FOR EXAMPLE TO ANY LANGUAGE
RELATED TO LAIV AND IIV.
EVEN IF THERE WERE NOT TO BE A
PREFERENCE.
WE'VE DONE THE GRADE ANALYSIS
AND WILL HAVE SOME SORT OF
SUMMARY OF THAT EITHER IN OR
LINKED TO THE POLICY NOTE.
BECAUSE POLICY NOTE IS SUCH A
SHORT-FORMAT DOCUMENT THERE WILL
PROBABLY BE A URL-LINK IN THE
DOCUMENT.
TYPICALLY THE ENTIRE DOCUMENT IS
NOT PUT INTO THE MMWR.
A COUPLE OF PRESENCES BACK.
ONE ISSUE THAT IS HARMONIZATION
WITH AAP IS SOMETHING WE AIM FOR
AND THE AAP WILL NOT BE MEETING
ON THIS TOPIC UNTIL APRIL.
>> DR. DUSHEN?
THANKS, LISA FOR YOUR
MULTIPLE PRESENTATIONS THIS
MORNING.
I JUST WANT TO FOLLOW UP ON THE
ISSUE OF PREFERENTIAL
RECOMMENDATION FOR LAIV AND FOR
OUR COLLEAGUES ON THE ACIP WHO
AREN'T PART OF THE INFLUENZA
WORK GROUP.
IT MIGHT HAVE BEEN A LITTLE BIT
VAGUE.
YOU KNOW REALLY STRONGLY
CONSIDER I
CONSIDERING PREFERENTIAL
RECOMMENDATION AND IT WOULD BE
GREAT IF THEY COULD
THAT IN THE TIME BETWEEN NOW AND
JUNE SINCE WE WON'T HAVE THE
OPPORTUNITY TO VOTE ON THAT
TODAY.
MANY OF US FEEL IT'S LONG
OVERDUE.
AND WE HAVE A VACCINE THAT EVEN
CDC HAS ACKNOWLEDGED ON A PUBLIC
WEB PAGE IS SUPERIOR.
IN YOUNG CHILDREN, YET WE
HAVEN'T GOT ENOUGH TO MAKE THE
RECOMMENDATION, WHICH DOES
INFLUENCE A LOT OF HEALTH CARE
PROVIDERS.
I WANT TO MAKE SURE OTHER
COLLEAGUES UNDERSTAND THAT
THAT'S UNDER SERIOUS
CONSIDERATION FOR THE JUNE
MEETING.
>> I'D LIKE TO FOLLOW UP ON THAT
POINT.
JUST A LITTLE BIT AS WELL.
AND THEN ALSO HAVE A QUESTION.
BUT THE POINT IS WHETHER OR NOT
THE ACIP MEMBERS WOULD REQUEST
OF THE INFLUENZA WORK GROUP
PROCEED WITH LANGUAGE AND SUCH A
RECOMMENDATION FOR A
PREFERENTIAL USE OF VACCINE.
KEEPING IN MIND ALSO JUST THE
TIMING FOR CLINICIANS AND HEALTH
SYSTEMS TO DO ORDERING THAT
LAST-MINUTE THINGS, YOU KNOW,
IDEALLY WHEN I PUT ON MY
CLINICIAN HAT.
THINGS COMING IN OCTOBER IS
APPROPRIATE FOR THE KIND OF THE
FOLLOWING YEAR FOR ORDERING.
SOY THINK WE JUST KEEP THAT IN
MIND.
THAT SAID, THE FOLLOW-UP
QUESTION I THINK IS FOR DR.
DEUTSCHEN AND ALSO FOR DR.
NEWSLE.
BOTH FROM STATE OF WASHINGTON,
WHERE YOU HAVE A PREFERENTIAL
RECOMMENDATION.
FOR THE LIVE ATTENUATED IN
CHILDREN.
CAN YOU PROVIDE US A LITTLE BIT
MORE INFORMATION ON THAT?
>> I PRESUME YOU'RE REFERRING TO
THE IMPACT THAT IT MIGHT HAVE
HAD ON THE USE OF THE LAIV?
YEAH, UNFORTUNATELY OUR
RECOMMENDATIONS DON'T CARRY THE
WEIGHT OF A RECOMMENDATION FROM
THE ACIP.
AND IT'S NOT REALLY CLEAR THAT
THEY HAVE THE PENETRATION THAT
WE WOULD DESIRE THROUGHOUT THE
CLINICAL COMMUNITY.
I LIKE TO TAKE THE OPPORTUNITY
ALWAYS TO REMIND OUR CLINICAL
COLLEAGUES THAT THERE ARE DATA
THAT SUGGEST THAT THE LAIV IS
BET ANYWHERE YOUNGER CHILDREN.
THAT THE CDC HAS MORE OR LESS
ENDORSED THAT DATA BY BOOSTING
THAT ON THEIR OWN WEBSITE
WITHOUT MAKING THE FORMAL
RECOMMENDATION.
SO IN THE CONTEXT OF ORDERING
VACCINE, I THINK CLINICIANS
SHOULD KEEP IN MIND, THAT THERE
ARE ALREADY, THERE'S ALREADY
DATA AVAILABLE TO SUGGEST THAT'S
A WISE THING TO DO FOR CHILDREN.
WE DON'T HAVE A SIGNIFICANT
CUTOFF YET, WHICH WOULD BE
USEFUL FOR SOME.
THERE HASN'T BEEN ANY ISSUE OF
SHORTAGE.
THE SUPPLY HAS BEEN ADEQUATE.
MANY CLINICIANS ARE AWARE, BUT
DO WAIT FOR A MORE CLEAR
GUIDANCE FROM THE ACIP BEFORE
SORT OF CHANGING THE LARGE
SYSTEM PRACTICES.
>> I THANK YOU.
DR. HARRISON?
>> I KNOW THE MEETING IS IN
APRIL BUT CAN WE GET A SENSE OF
WHERE AAIP IS ON THIS ISSUE?
WE HAVEN'T REALLY DISCUSSED
IT.
WE'RE GOING TO DISCUSS IT IN
APRIL AS MENTIONED.
I CAN TELL YOU THAT I CAN TELL
YOU THAT I CAN'T TELL YOU THAT
THERE'S A CONSENSUS YET AMONGST
THE GROUP.
SOME OF THE INFORMATION IS JUST
GOING TO BE PRESENTED FOR THE
FIRST TIME AT THE MEETING.
>> THANK YOU.
WE HAVE DR. KEMP?
>> YEAH, I THINK THAT THE DATA
SEEMS PRETTY STRONG.
I THINK THAT ONE THING I'M
WONDERING ABOUT IS I THINK IF IN
FACT THERE'S A PREFERENTIAL
RECOMMENDATION MADE, IT'S GOING
TO PUT FRONT AND CENTER THIS
ISSUE OF WHEEZING.
AND YOU KNOW, AS WELL-DEFINED
ASTHMA IS FAIRLY STRAIGHTFORW D
STRAIGHTFORWARD.
BUT AS ANY OF THE PRIMARY CARE
PROVIDERS IN THIS ROOM KNOW, IN
YOUNG CHILDREN, THERE'S A LOT OF
KIDS THAT HAVE WHEEZED OR HAVE
WHEEZED IN THE LAST YEAR.
BUT DO NOT HAVE A DIAGNOSIS OF
ASTHMA.
I THINK ANYTHING IF WE MAKE SUCH
A PREFERENTIAL RECOMMENDATION, I
WOULD LIKE TO DISCUSS A LITTLE
BIT MORE WHERE THE CURRENT ION,
CONTRAINDICATION, CAME FROM.
AND WHETHER WE CAN PIN THAT DOWN
A LITTLE BIT BETTER, GIVEN DATA
OF WHATEVER TYPE FROM OTHER
COUNTRIES, FOR EXAMPLE.
DR. BENNETT?
>> THANK YOU.
LISA, I JUST WANTED TO CLARIFY
WHAT YOU WERE SAYING ABOUT THE
RECOMMENDATIONS, THE YEARLY MMWR
ON INFLUENZA.
WERE YOU SAYING IF WE MADE A
PREFERENTIAL RECOMMENDATION IN
JUNE, THAT IT WOULD BE TOO LATE
FOR RECOMMENDATION?
OH NO.
NO.
WE'VE HAD, WE'VE HAD VOTES IN
JUNE I THINK ACTUALLY AS LONG AS
I'VE BEEN DOING THIS.
WE'VE HAD VOTES IN JUNE DESPITE
TRYING NOT TO HAVE VOTES IN
JUNE.
AND I APOLOGIZE FOR THAT.
BUT IT JUST SEEMS TO HAPPEN.
IT IS, IT IS TOO LATE IN THE
SENSE THAT ORDERING HAS HAPPENED
BY THAT POINT.
BUT ON THE OTHER HAND, BECAUSE
THERE'S ALWAYS SO MUCH GOING ON
WITH FLU, WE ONE MIGHT MAKE THE
ARGUMENT WE SORT OF HAVE TO
CONSIDER THINGS AS THEY COME
ALONG AND TRY TO KEEP THINGS
MOVING.
IT WOULDN'T BE TOO LATE TO GO
INTO THE MMWR.
AMONG THE CONCERNS THAT PEOPLE
HAVE EXPRESSED ABOUT HAVING A
PREFERENCE ON THE WORK GROUP, IF
I MAY SUMMARIZE, THERE'S THE
FACT THAT ORDERING WILL HAVE
HAPPENED ALREADY.
SO HARD TO IMPLEMENT FOR THE
14-15 SEASON.
ON THE OTHER HAND, THERE'S
PRECEDENT FOR EXAMPLE, I CAN'T
REMEMBER EXACTLY WHEN IT WAS, IT
PREDATES MY INVOLVEMENT IN THE
SOMEWHAT.
BUT AS THE RECOMMENDATION FOR
VACCINATION WAS BEING EXPANDED
INTO BROADER RANGES WITHIN THE
PEDIATRIC AGE GROUP, THERE WAS A
YEAR WHEN THE RECOMMENDATION WAS
VACCINATE THE AGE GROUP IF
FEASIBLE THIS SEASON IMPLEMENT
COMPLETELY BY THE FOLLOWING
SEASON.
THAT'S ONE THING THAT CAN BE
DONE THERE, IF THAT'S THE CASE.
MICROPHONE, PLEASE?
>> MEDICAL AFFAIRS.
THANK YOU SO MUCH FOR THE GREAT
PRESENTATIONS, GREAT WORK.
WE WOULD JUST WONDERING WHEN WE
WOULD INCLUDE THE -- RESULTS OF
THE 3-8-YEAR-OLDS, WHEN THAT'S
GOING TO BE PRESENTED.
THE QUESTION IS RELATED TO
WHEN WE WILL HAVE ALSO A REVIEW
OF THE DATA AVAILABLE FOR THE
QUADRIVALENT VACCINE AND THE
RECENT STUDY JUST PUBLISHED WITH
RELATION TO THE EFFICACY OF
QUADRIVALENT VACCINE IN THE
POPULATION.
SO QUADRIVALENT VERSUS
TRIVALENT?
YES.
>> AS USUAL WITH FLU, THERE ARE
A LOT OF TOPICS TO BE DISCUSSED.
AND THAT IS SOMETHING WE WILL
LIKELY BE DISCUSSING AT A FUTURE
DATE.
I CAN'T SAY EXACTLY WHEN.
>> DR. LAEHR.
AS A MEMBER OF THE WORK GROUP
I GUESS I RESPECTFULLY DISAGREE
WITH DR. TEMTE AND FOCUS MOSTLY
ON CAN'T WE JUST GET A
PREFERENTIAL RECOMMENDATION
AGREED UPON OR NOT AND NOT WORRY
ABOUT THE WHEEZING ISSUE AT THE
TIME AND ASK THE ACIP TO GIVE
GUIDANCE TO THE WORK GROUP, WHAT
WOULD YOU NEED TO FEEL
COMFORTABLE VOTING ON A
PREFERENTIAL RECOMMENDATION IN
JUNE.
BECAUSE THAT'S WHAT THE WORK
GROUP IS WRESTLING WITH RIGHT
NOW.
MY UNDERSTANDING THAT THERE
HADN'T BEEN A PREFERENTIAL
RECOMMENDATION ARE THERE OTHER
ISSUES YOU WOULD LIKE US TO
EXPLORE BEFORE WE BRING THIS
BACK IN JUNE.
AS MANY OF US FEEL WE WOULD LIKE
TO HAVE A VOTE ON THIS.
AND WITH SOME LANGUAGE FOR A
PREFERENTIAL RECOMMENDATION IN
JUNE.
>> DR. HARRISON?
DR. RUBIN, I'M SORRY.
>> I'M PRETTY MUCH COMPELLED
WITH THE DATA, AS DISCUSSED IN A
PREVIOUS MEETING, ONE OF THE
HANG-UPS WAS QUADRIVALENT LAIV
WAS A NEW PRODUCT.
AND SO I GUESS I'D LIKE TO AT
LEAST SEE THE DATA AS MENTIONED
EARLIER TONED DOWN ON THE AGE
GROUP, THAT WE MIGHT BE
POTENTIALLY BE GIVEN A
PREFERENTIAL TO SEE IF THERE'S
SIGNALS FOR SEIZURES ON
PARTICULAR.
AND FOR QUADRIVALENT AND
ACTIVATED VACCINE AS WELL IF
THERE'S SUFFICIENT DATA TO MAKE
THAT POINT.
DR. BOCCHINI.
>> JUST HARMONIZATION IS REALLY
IMPORTANT SO WE HAVE A SINGLE
MESSAGE.
I'D REALLY LIKE TO SEE WHAT THE
REVIEW AND WE COULD POTENTIALLY
GO FORWARD TOGETHER IN A A
HARMONIZED WAY.
I THINK THAT'S A VERY
REASONABLE APPROACH AND IF
THERE'S ANYTHING THAT WE CAN DO
TO FACILITATE GETTING THE
G.R.A.D.E. INFORMATION TO COID,
THAT WOULD BE WONDERFUL.
RUTH IS GOING TO DO THAT.
>> AT THIS TIME I THINK WE DO
HAVE THE POTENTIAL FOR A VOTE
FOR THE RECOMMENDATIONS AS
PRESENTED BY DR. GROHSKOPF.
I'M WONDERING IF THERE'S ANY
MOTION FOR THAT?
A MOVE BY DR. BOCCHINI, AND A
SECOND BY DR. DEUTSCHEN.
ANY DISCUSSION?
JUST LIMITED TO THE -- ACTUALLY
IF YOU CO
YOU HAVE A COMMENT, DR. KARRON?
>> YES, I THINK THAT THE
RECOMMENDATIONS AS THEY WERE
SENT TO US HAD A SORT OF A RED
HIGHLIGHT FOR ISSUES RELATED TO
CONTRAINDICATIONS WITH RESPECT
TO LAIV.
AND I THINK THAT THAT WAS AN
ISSUE THAT THE WORK GROUP WAS
GOING TO SPECIFICALLY TAKE UP
AND THAT MIGHT COME UP IN
OUR JUNE MEETING AND SO AS WE
VOTE ON THIS, I DON'T KNOW IF
THERE IS A WAY TO INCORPORATE
THE FACT THAT WE'RE, BECAUSE
THOSE ARE PART OF THE ANNUAL
RECOMMENDATIONS, AND YET WE MAY
RECONSIDER THOSE.
SO I DON'T KNOW THE BEST WAY TO
APPROACH THAT.
I THINK WE CAN JUST, AS PART
OF THE MINISTER, MAKE A STRONG
SUGGESTION TO THE WORK GROUP TO
CONSIDER THOSE ISSUES.
AS OPPOSED TO PUTTING IT IN THE
RECOMMENDATION PER SE.
I GUESS MY QUESTION IS, IF I
VOTED YES, AM I VOTING
APPROVE THE CURRENT
RECOMMENDATIONS FOR LIMITATIONS
OF USE AND HOW DOES THAT WORK?
>> MAY I COMMENT?
AT LEAST BASED ON MY
UNDERSTANDING OF, AND PLEASE,
DR. TEMTE AND DR. PICKERING,
CORRECT ME.
WHAT DR. KARRON IS REFERRING TO
IS THERE HAS BEEN FOR THE LAST
SEVERAL SEASONS, A FOOTNOTE IN
THE TABLE OF AVAILABLE VACCINES,
THAT CONCERNS ONE OF THE ISSUES
WE'VE DISCUSSED IN THE LAST
COUPLE OF PRESENTATIONS
SURROUNDING GROUPS FOR WHICH
THERE'S A PRECAUTION AGAINST
LAIV USE FOR EXAMPLE FOLKS WITH
CHRONIC MEDICAL CONDITIONS, AND
ARE ALSO SOME WORDING RELATED TO
ASTHMA.
AND THAT TABLE IN THE VERSION
YOU'VE SEEN OR THE FOOTNOTE IN
THE VERSION YOU'VE SEEN IS RED
AND MARKETED WITH A COMMENT
INDICATING THERE'S GOING TO BE
FURTHER DISCUSSION OF THAT
BETWEEN THIS MEETING AND THE
NEXT.
MY FURTHER UNDERSTANDING IS THAT
ALSO THERE'S OPPORTUNITY TO MAKE
CHANGES AT ANY POINT IF THAT'S
NECESSARY, AND IF THE COMMITTEE
VOTES ON IT.
FOR EXAMPLE, WE TEND TO HAVE
UPDATES TO THE TABLE BASED ON
NEW PACKAGE INSERTS AND OTHER
INFORMATION.
BUT THAT, THAT SECTION IS MARKED
AS BEING CURRENTLY UNDER
DISCUSSION.
>> IS THERE ANY COMMENT, DR.
SUN, FROM FDA REGAARDING?
>> I'M NOT SURE WHAT
SPECIFICALLY YOU WERE ASKING
COMMENTS ON.
CURRENTLY THERE IS A PACKAGE
INSERT WHICH STATES THE
CONTRAINDICATIONS AND THE
PRECAUTIONS AND SO ON.
AND MY SUSPICION IS THOSE WOULD
NOT BE CHANGED AT ALL.
THOSE ARE STANDING.
>> YES, JUST BY WAY OF KIND OF
BACKGROUND.
THERE ARE ONLY CERTAIN WAYS IN
WHICH WE CAN REVISE THE LABEL,
PACKAGING INSERT.
AND THOSE, THE MOST COMMON WAY
IS WHEN PRESENTED WITH DATA FROM
THE MANUFACTURERS CONCERNING THE
CHANGE.
THE SECOND METHOD IS THAT
THERE'S SPECIFIC SAFETY CONCERN
THAT ARE RAISED, THAT HAVE COME
TO BE KNOWN AND THEY'RE SUCH
SERIOUSNESS THAT NEEDS TO BE IN
THE LABEL.
IN WHICH CASE, FDA CAN MAKE A
SAFETY LABEL CHANGE SO THOSE ARE
THE ONLY REALLY TWO MECHANISMS
TO CHANGE THE LABEL.
UNLESS PRESENTED WITH
ADDITIONAL DATA ON THE WHEEZING
AND FLU MIST.
WE'LL HAVE TO LOOK AT THE DATA
AND CONSIDER WHAT THAT
IMPLICATION WOULD BE FOR ANY
CHANGES IN THE LABEL.
SO IF THERE'S NO -- YOU KNOW,
AND MEDIMMUNE CAN PROBABLY
COMMENT ON THIS WHETHER THEY
PLAN ON SUBMITTING SUCH DATA OR
WORKING WITH US TO DEVELOP SOME
DATA.
>> DR. KIRK?
JUST TO THE POINT OF
CLARIFICATION, RIGHT NOW THE
LABEL FROM THE FDA HAS FAIRLY
NARROW CONTRAINDICATIONS AND
KATHY ACTUALLY EXPLAINED WHAT
THOSE WERE.
THE CURRENT ACIP RECOMMENDATIONS
AS I READ THEM LUMP TOGETHER THE
CONTRAINDICATIONS AND THE
PRECAUTIONS.
AND SO I THINK THAT THE QUESTION
THAT THE WORK GROUP REALLY WANTS
TO WORK ON, IS SHOULD THOSE IN
FACT BE LUMPED TOGETHER AS ONE.
OR SHOULD WE PRECAUTIONS ARE
DIFFERENT FROM CONTRAINDICATIONS
AND SHOULD WE CONSIDER THOSE
SEPARATELY.
THAT WOULDN'T REQUIRE SOMETHING
SPECIFICALLY FROM THE FDA.
THAT WOULD REQUIRE US TO REVIEW
WHAT'S ALREADY IN OUR
RECOMMENDATIONS.
>> DR. KIM?
YEAH, JUST DO CLARIFY FROM
THE COMMENT FROM THE AAFP.
I THINK THAT THIS, I PERSONALLY
HAVE ENOUGH INFORMATION TO BE IN
FAVOR OF MAKING RECOMMENDATION
IN JUNE.
BUT I DO THINK IT'S IMPORTANT TO
MORE SPECIFICALLY GET INTO THIS.
BECAUSE IT IS GOING TO PUT IT
FRONT AND CENTER.
SO I DIDN'T MEAN TO IMPLY THAT
THAT WOULD HOLD UP THE DECISION.
DR. RUBIN?
>> I WOULD JUST LIKE DO CLARIFY
WHAT WE'RE BEING ASKED TO VOTE
ON NOW.
AS BEST I CAN TELL IT'S A
REAFFIRMATION OF LAST YEAR'S
STATEMENT WITH CHANGING 13-14,
DO 14-15.
AND NEW PLAYERS TO BE NAMED
LATER OR SOMETHING.
YEAH.
>> I THINK YOU'RE CALLING THAT
CORRECTLY.
I SAW ONE HAND UP WITH DR. SUN?
I WANT TO FOLLOW UP WITH WHAT
DR. KARRON HAD SAID, AND PERHAPS
IT MAY BE USEFUL TO MAKE A
DISTINCTION BETWEEN
CONTRAINDICATIONS AND WARNINGS
AND PRECAUTIONS IN THE PACKAGE
INSERT.
SO WE DO HAVE OF COURSE HAVE
VERY SPECIFIC DEFINITIONS OF
THOSE.
AND SO PLEASE BEAR WITH ME IF I
COULD JUST DESCRIBE THAT A
CONTRAINDICATION ACCORDING TO
THE FDA IS WE'RE DESCRIBING ANY
SITUATION IN WHICH A DRUG SHOULD
NOT BE USED BECAUSE THE RISK
CLEARLY OUTWEIGHS ANY POSSIBLE
BENEFIT.
AND THAT THERE IS SUCH STANGS
RISK OF BEING HARMED FOR THE
PATIENT.
FOR WHOM THERE'S NO POTENTIAL
BENEFIT MAKES THE RISK
ACCEPTABLE.
AND THESE ARE, ARE SUPPOSED TO
BE KNOWN HAZARDS, NOT
THEORETICAL POSSIBILITIES,
WHEREAS WARNINGS OR PRECAUTIONS
IN MERELY DESCRIBES CLINICALLY
SIGNIFICANT INFORMATION.
INFORMATION THAT WOULD AFFECT
DECISION ON WHETHER TO PRESCRIBE
THAT DRUG.
AND ALSO, ANY RECOMMENDATION
MONITORING THAT ARE CRITICAL TO
SAFE USE OF THE DRUG.
AND THEN ANY MEASURES THAT CAN
BE TAKEN TO PREVENT OR MITIGATE
HARM.
IT'S VERY DIFFERENT FROM A
CONTRAINDICATI
CONTRAINDICATION, IN THAT ONE
THE RISK/BENEFIT MAY BE VERY
DIFFERENT.
AND I THINK THAT'S A JUDGMENT
CALL BASED ON THE ADVISORY
COMMITTEE OR THE HEALTH
DEPARTMENT.
THANK YOU.
FURTHER, UP AT THE MICROPHONE?
SURE, CHRIS AMBROSE IN
MEDICAL AFFAIRS, MEDIMMUNE.
TO RESPOND TO THE REQUEST BY DR.
SUN FOR DATA, WE HAVE AN ACTIVE
SUBMISSION WITH THE FDA WILDFIRE
WE'VE SUBMITTED THE DATA FROM
THE FLEMING STUDY, IT HAS SAFETY
DATA IN CHILDREN WITH ATHS MARKS
AS WELL AS CHILDREN FROM THE
BELSHI STUDY AND THE ASHKANAZI
STUDY IN WHICH CHILDREN HAVE A
HISTORY OF WHEEZING OR ASTHMA.
AND WE'RE IN CONVERSATIONING
WITH THE FDA ABOUT THAT SO WE
LOOK FORWARD TO WORKING WITH
THEM TO SEE THE RESOLUTION OF
THAT SUBMISSION.
>> PATSY STINCHFIELD.
THE REASON I RAISED THIS IS TO
PLAY IT OUT AND WE HAVE A
PREFERENTIAL LAIV, BUT WE USE
OUR EXISTING LANGUAGE THAT
PRECLUDES US FROM USING IT IN
CHILDREN WITH METABOLIC
DISORDERS, I AS A CLINICIAN AM
GOING TO HAVE A HARD TIME
TALKING TO A DIABETIC AND SAY
THIS IS A BETTER VACCINE, BUT
YOU CAN'T HAVE IT BECAUSE YOU'RE
NOT CONSIDERED HEALTHY.
SO WHEEZING ASIDE, I JUST THINK
WE HAVE TO REALLY BE CLEAR ABOUT
OUR TRUE CONTRAINDICATIONS AND
THOSE PRECAUTIONS THAT WOULD
ALLOW US TO OPEN IT UP FOR USE
MORE.
I AM REPRESENTING THE ACP AND
THE AMA, AS A CLINICIAN, I THINK
YOU POINTED OUT WE HAVE TO DO
OUR ORDERING NOW.
AND I THINK IT'S GOING TO PUT
CLINICIANS IN SORT OF A, A
STRANGE PLACE.
IF YOU ORDER NOW AND YOU ORDER
BASED ON THE CURRENT
RECOMMENDATIONS AND THEN COME
JUNE, WHAT YOU'VE ORDERED IS NOT
WHAT'S RECOMMENDED.
AND OR THAT POSSIBILITY.
SO I -- IT DOES PUT CLINICIANS
IN A WEIRD POSITION.
>> DR. DUSHEN?
THANK YOU.
TWO COMMENTS, ONE TO FOLLOW UP
ON PATSY STINCHFIELD.
I COMPLETELY AGREE AND I THINK
THAT WILL BE THE TEST THAT A
WORKING GROUP COME FORWARD TO
CLARIFY THAT LANGUAGE AND TO
ADDRESS THOSE CONCERNS WHICH
MANY OF US FEEL ARE NOT
BENEFICIAL RIGHT NOW.
THAT'S THE WAY THEY'RE DESCRIBED
IN THE STATEMENT.
AND THEN JUST SECONDLY AROUND
THE ISSUE OF ORDERING.
FOR MY PERSPECTIVE, WE DO A LOT
OF ORDERING IN THE PUBLIC HEALTH
DEPARTMENT, WE ADVISE CLINICIANS
ON ORDERING, WE'RE A UNIVERSAL
STATE.
THERE'S ALWAYS A PROBLEM WITH
ORDERING.
THINGS NEVER SYNCHRONIZE.
SO WE HAVE TWO GOOD VACCINES OUT
THERE FOR CHILDREN.
SOME CLINICIANS ALREADY KNOW
THAT LAIV MAY BE BETTER IN
YOUNGER CHILDREN AND THEY CAN
TAKE THAT INTO ACCOUNT WHEN THEY
ORDER NOW AND THEY CAN
ANTICIPATE THEY MAY BE SEEING
SOME MORE STRIDENT OR MORE
DIRECTIVE LANGUAGE FROM ACIP ON
THIS.
IT'S NOT GOING TO PUT THEM IN A
VERY POOR POSITION TO HAVE YOU
KNOW, MORE OR LESS LAIV VERSUS
IIV.
EITHER WAY, BECAUSE BOTH
VACCINES ARE GOOD.
AND THERE'S ALWAYS A TRANSITION
PERIOD WHEN NEW RECOMMENDATIONS
ARE MADE BEFORE EVERYBODY COMES
ON BOARD.
SO I THINK YOU KNOW, PEOPLE MAY
NOT HAVE THE OPTIMAL MIX THEY
WOULD DESIRE, BUT THEY CERTAINLY
WILL HAVE GOOD VACCINES THEY CAN
USE ON ALL THEIR PATIENTS,
EITHER WAY.
>> DOES THAT GIVE ENOUGH
FEEDBACK TO THE WORK GROUP TO
BRING THINGS BACK IN JUNE?
VERY GOOD.
THE OTHER POINT I'LL JUST THROW
OUT REALLY QUICKLY.
IN MY MIND THE BIGGEST PROBLEM
OUT THERE IS WE UNDERUTILIZE
INFLUENZA VACCINES IN GENERAL
FOR CHILDREN.
AND ESPECIALLY IN SCHOOL-AGED
CHILDREN.
SO IS THERE ANY FURTHER
DISCUSSION?
WHY DON'T WE GO AHEAD AND DO A
VOTE.
WE'LL START WITH DR. RHINEGOLD
AND GO TO YOUR RIGHT.>> I VOTE IN FAVOR.>> I VOTE YES.
KARRON, YES, WITH A PRO
ADVISO THAT WE EXPECT SOME OF
THE ISSUES WE DESCRIBED.
>> YES.
TEMTE YES.
>> BENNETT, YES.
PELLEGRINI, YES.
>> RUBIN, YES.
HARRISON, YES.
>> VASQUEZ, YES.
BEASLEY, YES.
>> JENKINS, YES.
KEMP, YES.
>> BOW KEENI, YES.
THANK YOU, THE VOTE IS
UNANIMOUS, I DON'T BELIEVE
THERE'S ANY -- PARDON?
>> I ALREADY DID.
I DON'T BELIEVE THERE'S ANY VSD
RESOLUTION THAT NEEDS TO GO WITH
THIS BECAUSE IT'S ALREADY
EXISTING.