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>>>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 ***, ORAL OR AXILLARY, ORAL OR ***
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.