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>> LET ME ASK DR. BOCCHINI TO
KICK OFF THE SESSION ON JAPANESE ENCEPHALITIS VACCINE.
FOLLOWING THE DISCUSSION FROM INTERCELL BIOMEDICAL WE'LL OPEN
IT UP FOR SOME QUESTIONS BEFORE MOVING ON TO THE GREAT
DISCUSSION. >>> GOOD MORNING.
I'M PLEASED TO START THIS DISCUSSION OF THE USE OF
JAPANESE ENCEPHALITIS VACCINE IN CHILDREN WITH AN OVERVIEW OF THE
WORK OF THE WORK GROUP AND SOME BACKGROUND INFORMATION WHICH
PROVIDES YOU THE KEY ISSUES WILL COME BEFORE THE ACIP TODAY.
AN ACTIVATED BUREAU CELL CULTURE DERIVED JV VACCINE IS THE ONLY
VACCINE LICENSED AND AVAILABLE IN THE LICENSE.
IN JE-VC WAS LICENSED FOR USE IN ADULTS 17 YEARS OF AGE
AND OLDER. ON MAY 17th, THIS YEAR, THE FDA
LICENSED JE-VC FOR USE IN CHILDREN TWO MONTHS
YEARS OF AGE. SO TODAY WE WILL PRESENT THE
EVIDENCE REVIEW, THE GRADE EVALUATION OF THE EVIDENCE AND
PROPOSED RECOMMENDATIONS FOR USE OF JE-VC IN CHILDREN FOR
DISCUSSION BY THE ACIP. NOW JE-VC IS MANUFACTURED BY
INTERCELL BIOMEDICAL. IT'S DISTRIBUTED IN THE UNITED
STATES PRIVATE MARKET BY NOVARTIS VAC SEE VACCINE AND IT
INDICATED FOR THE ACTIVE IMMUNIZATIONS TO PREVENT DISEASE
CAUSED BY JE VIRUS. THE DOSE AND ADMINISTRATION IS
LISTED HERE. FOR CHILDREN 2 MONTHS THROUGH 2
YEARS OF AGE, IT IS .25 ML. FOR CHILDREN 3 YEARS OF AGE AND
OLDER, AND ADULTS, IT IS .5 ML PER DOSE.
THE PRIMARY SERIES IS TWO DOSES ADMINISTERED 28 DAYS APART.
NOW THERE IS NO EFFICACY DATA FOR JE-VC.
THE AVAILABLE OF SEVERAL EFFECTIVE JE VACCINES IN ASIA
MADE COMPARATIVE EFFICACY TRIALS DIFFICULT TO PERFORM.
HOWEVER, THERE IS AN ESTABLISH IMMU
IMMUNEO LOLIC. 10 OR GREATER IS CONSIDERED TO
BE PROTECTIVE AGAINST JE INFECTION.
NOW JE-VC WAS LICENSED IN ADULTS BASED ON NON-INFERIORITY TRIALS
OF NEUTRALIZED ANTIBODY RESPONSE, COMPARED TO A LICENSED
MOUSE BRAIN DERIVED JE VACCINE, JE-MB.
AND IT WAS LICENSED BASED ON PROPORTION OF JE-VC RECIPIENTS
WHO ACHIEVED VIRUS PRNT 10 OR GREATER AS A CORRELATE OF
PROTECTION. THIS HAD A 91% EFFICACY IN A RON
D RANDOMIZED CONTROL CHOOIL TRIAL
IN THE MID 1980s. DURING THE LICENSING PROCESS OF
JE-VC IN ADULTS, BASIC EVALUATIONS WERE DONE ON
APPROXIMATELY 55,000 ADULTS IN CLINICAL TRIALS AND SINCE
LICENSURE OVER 300,000 DOSES OF JE-VC HAVE BEEN DISTRIBUTED IN
THE UNITED STATES. A REVIEWOMME RECOMMENDATIONS FOR THE USE OF
JE VACCINES IN U.S. INCLUDING JE-VC IN ADULTS 17
YEARS OF AGE AND AND A
RECOMMENDATION FOR THE INACTIVATED MOUSE BRAIN DERIVED
VACCINE, JE-MB FOR ADULTS AN CHILDREN 1 YEAR
OLDER. IN FEBRUARY 2011, THE ACIP
APPROVED BOOSTER DOSE OF JE-VAS YOU HEAR
LONGER MANUFACTURED OR AVAILABLE IN THE UNITED STATES.
DURING THE TIME PERIOD OF 2002 2,000 TO DOSES OF JE-MB WERE
DISTRIBUTED TO PROVIDERS EACH YEAR AND THAT --
IT IS DIFFICULT TO TRANSLATE THAT INTO THE NUMBER OF CHILDREN
WHO ARE IMMUNIZED BECAUSE NON-PEDIATRIC PROVIDER CERTAINLY
COULD HAVE GIVEN THE VACCINES TO CHILDREN WHO WERE TRAVELING AND
THEN THIS VACCINE JE-MB REQUIRED THREE DOSES FOR THEY
SERIES. HOWEVER, THE OPTIONS -- THE
JE-MB V REMAINING SUPPLY, BECAME OUTDATED.
THE DATE EXPIRED IN MAY OF 2011 SO THE VACCINE WAS NO LONGER
AVAILABLE AT ALL FOR CHILDREN AND THECDC PUB ACCOMPLISHED AN
PERTAINING TO THE JE VACCINE FOR CHILDREN OUTSIDE OF THE COUNTRY
WHO WERE TRAVELING. SO T VACCINE WORK GROUP WAS
REACTIVATED IN OCTOBER 2012. THE WORKING GROUP HAS MET 13
TIMES TO DISCUSS ISSUES RELATED TO JE-VC IN CHILDREN.
WE REVIEWED THE EPIDEMIOLOGY OF JE INFECTION IN TRAVELERS, THE
SAFETY AND IMMUNOGENICITY. WE'LL PRESENT RECOMMENDATIONS
TODAY TO ACIP. WE'VE GIVEN TWO PREVIOUS
PRESENTATIONS TO ACIP ON THIS TOPIC.
THE FIRST IN OCTOBER OF 2012 TO INDICATE THE WORK GROUP CHARGE
AND ITS PLANS. AND THEN IN FEBRUARY OF THIS
YEAR, DISCUSSED JAPANESE ENCEPHALITIS VIRUS AND ITS
INFECTIONS AND SEQUELLA AND THE USE OF JV VACCINE IN TRAVELERS.
I WANT TO THANK MEMBERS OF THE WORK GROUP.
THIS HAS BEEN A VERY ACTIVE WORK GROUP WITH CONTRIBUTIONS FROM
EACH OF ITS MEMBERS. PARTICULARLY WANT TO POINT OUT
LORI RUBEORY RUBEN AND MARC FISR FOR KEEPING US ON TASK FOR THIS
IMPORTANTRORY RUBEN AND MARC FI KEEPING US ON TASK FOR THIS
IMPORTANT PROCESS. TODAY WE'LL FIRST HEAR A
PRESENTATION FROM INTERCELL BIOCELL.
THIS WILL BE A REVIEW OF THE DATA SUBMITTED TO THE FDA WHICH
LED TO THE LICENSURE OF THE VACCINE.
FOLLOWING THAT PRESENTATION, THERE WILL BE AN OPPORTUNITY FOR
QUESTIONS FROM THE ACIP. FOLLOWING THAT DISCUSSION, MARC
FISCHER WILL PRESENT THE GRADE EVIDENCE -- THE REVIEW OF
EVIDENCE IN GRADE FOR USE OF VACCINE IN CHILDREN, AND THEN HE
WILL PRESENT THE PROPOSED RECOMMENDATIONS FOR USE OF THE
VACCINE IN CHILDREN, FOLLOWED BY DISCUSSION AND A VOTE.
THERE WILL BE NO EFC VOTE FOR THIS VAC EVEN.
>>> THANK YOU. GOOD MORNING.
AND IT IS REALLY A PLEASURE TO BE HERE AND BE ABLE TO PRESENT
THE PEDIATRIC DATA THAT BROUGHT LICENSURE OF THIS VACCINE TO
YOU. IT HAS BEEN POINTED OUT, THE
MANUFACTURER IS INTERCELL. HOWEVER, YOU WILL SEE A NEW NAME
ON THIS SLIDE HERE AND I'D LIKE TO JUST INFORM YOU THAT WE
RECENTLY COMPLETED THE MERGER WITH A NEW -- TO FORM A NEW
COMPANY. IN THE MID-TERM, THE
MANUFACTURER'S NAME WILL BE TRANSFERRED TO THIS NEW NAME
THAT YOU ALREADY CAN SEE ON THE SLIDE.
IN TOTAL I'M GOING TO PRESENT DATA FROM THREE CLINICAL TRIALS
TO YOU TODAY THAT WERE CONDUCTED LEADING UP TO LICENSURE.
THIS WAS ONE PHASE TWO STUDY CONDUCTED IN INDIAN TODDLERS
WHERE WE LOOKED TO CONFIRM THE DOSE OF VACCINE IN THE AGES FROM
1 YEAR TO 3 YEARS. AND THEN WE WILL SHOW DATA FROM
TWO PHASE THREE CLINICAL TRIALS, ONE CONDUCTED IN CHILDREN IN A
BIG AREA OF THE EUROPE, UNITED STATES AND AUSTRALIA.
CHILDREN THAT WERE TRAVELING TO AREAS IN ASIA.
THEN THE SECOND STUDY I'M GOING TO PRESENT ON IS A LARGE PHASE
THREE STUDY CONDUCTED IN THE PHILIPPINES.
STARTING WITH THE PHASE TWO TRIALS, AS I MENTIONED, THE
STUDY HAD THE OBJECTIVE TO CONFIRM THE DOSE USED IN
CHILDREN AGE 1 YEAR TO BELOW 3 YEARS.
STUDY WAS A RANDOMIZED CONTROLLED CLINICAL TRIAL IN 60
HEALTHY TODDLERS. THESE CHILDREN RECEIVED OVER
O'EITHER AN 0.25 DOSE OR 0.28. THIS REPRESENTS HALF OF THE
ADULT DOSE. OR AN 0.5 ML DOSE.
THEN WE HAD A CONTROL GROUP WHO RECEIVED A VACCINE PRODUCED A
MILD STRAIN. THIS IS LICENSED AND IS PRODUCED
IN KOREA. THE VACCINE IS MANUFACTURED TO A
SIMILAR TECHNOLOGY THAN THE FORMALLY U.S. LICENSED JE-VC.
THIS WAS GIVEN IN A THREE-DOSE SCHEDUL
SCHEDULE. THE STUDY LOOKED AT IMMU
IMMUNOGENICI IMMUNOGENICITY.
IN THE STUDY WE'VE SEEN RELATIVELY LIMITED PRE-EXISTING
IMMUNITY. ON DAY 28, FOUR WEEKS AFTER THE
FIRST DOSE, THE ZERO PROTECTION RATE RANGED ABOUT 16%, 17%.
WITHIN FOUR WEEKS, IT EXCEEDED 95% WITH BOTH OF THE DOSES OF
VACCINE. LOOKING AT THE GEOMETRIC MEANS
IN RESPONSE TO THE COMPLETE IMMUNIZATION SCHEDULE HERE ON
DAY 56, WE SEE THAT THE HALF DOZE OF VACCINE AND FULL DOSE OF
VACCINE DID NOT REALLY DIFFER IN TERMS OF IMMUNOGENICITY AND WERE
ALSO VERY WELL COMPARABLE TO THE MUTUALLY ANTIBODY PRODUCED BY
THE THREE-DOSE COURSE OF THE MILD STRAIN OF VACCINE.
THERE WAS NO INDICATION THAT THE HIGHER DOSE WOULD BE OF BENEFIT
FOR THE CHILDREN. LOOKING AT THE SAFETY RESULTS
FOR THE HALF DOSE AND THE FULL DOSE, WE SEE THAT BOTH OF THE
DOSES WERE WELL TOLERATED. LOOKING AT OVERALL RATE, ABOUT
12% IN THE SUBJECTS TO RECEIVED
2.25 ML, THE ONLY REACTION SEEN IN MORE THAN ONE SUBJECT WAS
INGESTION BY TEI INJECTION WITH TENDERNESS.
BASED ON BOTH IMMUNOGENICITY AND SAFETY RESULTS WE DECIDED TO
CARRY THE 0.25 ML DOSE FORWARD FOR DEVELOPMENT IN THIS AGE
GROUP. THE SECOND STUDY I WILL PRESENT
DATA ON IS THE PHASE THREE CLINICAL TRIAL IN TRAVELING
CHILDREN. THIS STUDY WAS A CHALLENGE TO
CONDUCT BECAUSE OF THE POPULATION THAT HAD TO BE
ENROLLED. NOTORIOUSLY TRAVELERS TEND TO
PRESENT VERY LATE FOR IMMUNIZATIONS AND IT WAS REALLY
VERY CHALLENGING TO INCLUDE CHILDREN WHO WERE ABLE TO GET
BOTH VACCINATIONS AND WHO WOULD BE PRESENT FOR A FOLLOW-UP VISIT
FOUR WEEKS AFTER THE SECOND DOSE OF VACCINE.
THE DATA I AM SHOWING FROM THIS STUDY ARE DATA FROM AN INTERIM
IMMUNE NOLL GIST WHO COVERED 60 YEARS.
WE ENROLL THE ENTIRE AGE GROUP BETWEEN 2 MONTHS AND UP TO 17
YEARS OF AGE. THE STUDY WAS CONDUCTED AS AN
OPEN LABEL STUDY. IN TERMS OF RECRUITMENT, WE WERE
ABLE TO RECRUIT FIVE CHILDREN WHO WERE GOING TO RECEIVE THE.25
ML DOSE AND 55 CHILDREN RECEIVED THE .5 ML DOSE BASED ON THEIR
AGE. FOLLOW-UP WITH THIS STUDY
EXTENDED TO DAY 56 AND A VISIT AT MONTH SEVEN.FOLLOW-UP WITH T
EXTENDED TO DAY 56 AND A VISIT AT MONTH SEVEN.
AGAIN, LOOKING AT IMMUNOGENICITY, WE SAW NO
PRE-EXISTING IMMUNITY. NO CHILD WITH ANTIBODIES PRIOR
TO VACCINATION. ON DAY 56, THE ZERO PROTECTION
RATE REACHED 100%. AND WHILE THE DATA AT MONTH
SEVEN ARE LIMITED TO 18 SUBJECTS WHO HAD REACHED THIS TIME POINT,
WE SEE THAT ALL OF THESE SUBJECTS WERE ABLE TO RETAIN
THEIR PROTECTIVE -- LOOKING AT THE RESPECTIVE GEOMETRICS HERE,
WHAT YOU CAN SEE IS THAT ON DAY 56, WE GET GMTs IN THE RANGE OF
200, 300 WITH BOTH VACCINES. NO LOWER IMMUNOGENICITY WITH
THOSE. AS EXPECTED FROM THE RESULTS
WE'VE SEEN IN ADULTS, WE SEE A DECLINE IN NEUTRALIZING
ANTIBODIES AND THE RATE OF THE DECLINE IS COMPARABLE TO THAT
PROFILE IN ADULTS. NOW LET'S LOOK AT SAFETY RESULTS
IN THAT STUDY. SAFETY ANALYSIS IS BASED ON 60
SUBJECTS WHO RECEIVED AT LEAST ONE DOSE OF THE VACCINE.
OVERALL, THE PRIMARY END POINT FOR SAFETY IN THE TRIAL WAS THE
RATE OF SERIOUS ADVERSE EVENTS OR MEDICALLY ATTENDED ADVERSE
EVENTS. IN TOTAL THERE WERE THREE
CHILDREN OR A RATE OF 5% FOR SUCH ADVERSE EVENTS.
ALL OF THESE THREE ARE ACTUALLY MEDICALLY TENDED AS MOST SERIOUS
ADVERSE EVENTS OCCURRED UP TO DAY 56.
THE OVERALL RATE OF ADVERSE EVENTS IN THE TRIAL WAS 66% OF
CHILDREN HAD HAD ANY SOLICITED OR UNSOLICITED ADVERSE EVENTS.
NOW I AM GOING TO LOOK AT SOLICITED ADVERSE EVENTS FIRST
IN THE FIVE CHILDREN WHO RECEIVED THE 0.5 ML DOSE
VACCINE. DATA LIMITED HERE BUT WE HAVE
ONE CHILD WITH AN INJECTION AND REACTION.
TWO HAD INJECTION REACTIONS AFTER THE SECOND DOSE.
HARDENING AN REDNESS. WE HAVE SEEN DIARRHEA AS THE
ONLY SOLICITED SYMPTOM AS BOTH THOSE.
NOW LOOKING AT RESULTS FOR THE 0.15 ML DOSE WHERE THAT CORE OF
CHILDREN IS LARGER, THE LOCAL REACTIONS TO THE FIRST AND
SECOND DOSE OF VACCINE. SO AFTER THE FIRST DOSE OF
VACCINE, ABOUT 40% OF CHILDREN HAD ANY INJECTION SIDE REACTION.
THIS RATE WAS LOWER AFTER THE SECOND DOSE WITH ABOUT 27%.
COMPARABLE TO THE LOCAL IMMUNOGENICITY PROFILE, WE SEE
THE MOST COMMON REACTIONS AND THE ONLY REACTION IN MORE THAN
10% OF THE SUBJECTS. NOW MOVING OVER TO SOLICITED
SYSTEMIC REACTION, AGAIN WE SEE 42% OF CHILDREN HAVING ANY
SYSTEMIC REACTION FOR THE FIRST DOSE AND THE LOWER RATE WITH
ABOUT 16% FOR THE SECOND DOSE OF VACCINE.
MUSCLE PAIN AND EXCESSIVE FATIGUE WERE THE MOST COMMON
REACTIONS FROM THE FIRST DOSE AND ARE THE ONLY REACTIONS THAT
WERE SEEN IN GREATER THAN 10% OF THE SUBJECTS.
THERE WAS LOW RATE OF FEVER AND FEVER WAS MOAT LMOSTLY VERY MIL.
SO SUMMARIZING THIS STUDY, IT WAS IMMUNO GENIC AND PROTECTED
ANTIBODY TIGERS IN BOTH GROUPS. ALL OF THE SUBJECTS DEVELOPED
PROTECT I PROTECTIVE SITES AT DAY SIX.
DECLINED DOWN TO MONTH SEVEN. HOWEVER FOR DATA FOR SUBJECTS WE
ALREADY HAVE DATA ON, ALL OF THEM RETAINED PROTECTIVE TITLE
LEVELS. IT WAS ALSO WELL TOLERATED AS
BOTH DOSES UTILIZED IN THE STUDY, THE OVERALL PROFILE WAS
COMPARABLE WITH THAT FOR ADULT DATA -- FOR UNSOLICITED ADVERSE
EVENTS WE'VE ACTUALLY SEEN FEWER REACTIONS THAN IN ADULTS.
WITH THIS I'D LIKE TO MOVE OVER TO PRESENT THE THIRD CLINICAL
STUDY, THE TRIAL THAT WAS DONE IN THE PHILIPPINES.
THIS STUDY LOOKED AT SAFETY AND IMMUNOGENICITY OF THE VACCINE
AND IT ALSO INCLUDED A LITTLE COHORT WHERE WE AGAIN LOOKED TO
CONFIRM A DOSE IN CHILDREN AGE 3 TO 12 YEARS.
TRIAL WAS CONDUCTED AS A RANDOMIZED ACTIVE CONTROLLED
STUDY AND THE TOTAL NUMBER OF SUBJECTS WAS 1,869 CHILDREN.
AGAIN, WE RECRUITED FROM ALL AGE GROUPS FROM 2 MONTHS UP THROUGH
17 YEARS OF AGE. MAYBE ONE POINT OF THE
PHILIPPINES, WHILE THE COUNTRY IS INGENDEMIC FOR JE-VC, DOES N
HAVE A LICENSE AND IS NOT PART OF THE NATIONAL IMMUNIZATION
PROGRAM. SO WE COULD RECRUIT FROM ALL
AGES THERE. THE TREATMENT GROUPS WE HAD IN
THIS STUDY ARE BASICALLY THE GROUPS RECEIVED EITHER 0.5 ML IF
THEY WERE AGE 3 YEARS AND OLDER. THE 0.25 ML DOSE WAS AGAIN USED
FOR CHILDREN FROM 2 MONTHS OF AGE UP TO 3 YEARS.
I MENTIONED A LITTLE COHORT THAT RECEIVED THIS VACCINE AGED 3 TO
12 YEARS. WE HAD TWO YEARS, TWO DIFFERENT
CONTROL VACCINES, BECAUSE WE DIDN'T FINE THE ONE VACCINE THAT
WOULD BE LICENSED IN THE UNITED STATES AND WOULD BE APPROVED FOR
THE ENTIRE AGE RANGE FROM 2 MONTHS OF AGE UP TO THE 17
YEARS. SO WE ENDED UP USING A
CONTROLLED VACCINE IN CHILDREN AGED BELOW 12 MONTHS AND THE
SCHEDULE WAS VACCINATIONS ON DAY 0, 28, 56 AND THE THIRD OR
FOURTH DOSE AT LAST STUDY VISIT DAY 28 DOSE ADMINISTERED TO
CHILDREN BELOW 6 MONTHS AT ENROLLMENT.
AND FOR THE AGE GROUP AGE 1 YEAR AND OLDER, THE CONTROL VACCINE
WAS -- THE STUDY HAD A FOLLOW-UP AT 56 AND MONTH SEVEN FOR
IMMUNOGENICITY AND SAFETY. THE PRIME END POINT OF THE STUDY
WAS ADVERSE EVENTS UP TO DAY 56 AND IMMUNOGENICITY WAS ADDRESSED
IN A IS UP GROUP OF PATIENTS. THIS IS JUST A BRIEF STUDY
SCHEME BECAUSE OF THE DIFFERENT VACCINATION SCHEDULES WE HAVE
USED IN THE CONTROL GROUP. I JUST WANTED TO WALK YOU
THROUGH THE BET THAT DATA COLLECTION, AND THEN ON TO
VACCINATIONS WE'VE HAD IN THE STUDY.A DATA
COLLECTION, AND THEN ON TO VACCINATIONS WE'VE HAD IN THE
STUDY. BASICAL
AFTER EACH OF THE VACCINATIONS WE HAD A SUBJECT DIARY THAT
COVERED SEVEN DAYS FOLLOWING VACCINATION.
THE FIRST DOSE WAS GIVEN. THE SECOND DOSE WAS GIVEN AT THE
VERY LAST STUDY VISIT AND THERE WAS NO ADDITIONAL FOLLOW-UP
AFTER 60 MINUTES AFTER THAT SECOND DOSE.
FOR PRED MAR, AFTER THE FIRST DOSE AND 28 DAYS, THOSE THAT
WERE ADMINISTERED IS INCLUDED IN THE ANALYSIS UP TO DAY 56 DATA.
THE DIARY CARD FOR THE THIRD DOSE IS INCLUDED IN THE ANALYSIS
WITH DATA UP TO MONTH SEVEN. AND AGAIN THE LAST DOSE
ADMINISTERED AT THE LAST STUDY VISIT WE DO NOT HAVE ANY DATA
COLLECTED FOR THIS DOSE. NOW THIS SLIDE SHOWS YOU THE AGE
DISTRIBUTION OF THE STUDY POPULATION.
OVERALL WE RECRUITED 131 CHILDREN AGE BETWEEN 2 MONTHS
AND 1 YEAR AND THE COMPARATIVES IN THE AGE GROUP ARE 64 CHILDREN
WHO RECEIVED PREDMAR. THE AGE GROUP 1 TO S
IS THE LARGEST COHORT IN THE STUDY.
WE HAD 640 CHILDREN WHO RECEIVED A ZERO COMPARED TO 213 WHO
RECEIV RECEIVED.1 ML DOSE.
>>> THE ZERO PROTECTION RESULTS FIRST.
THIS IS AGAIN THROUGHOUT THE STUDY.
LOOKING AT THE 0.25 ML DOSE AND THE 0.5 ML DOSE, YOU CAN SEE WE
HAVE RELATIVELY LIMITED IMCOMMUNITY WITH YOUNGER GROUPS
RECEIVING THE.25 MILLION L DOSE. THIS RATE IS HIGHER WITH THE .5
ML DOSE. ON DAY 56 IN BOTH VACCINATION
GROUPS WE HAVE ZERO PROTECTION RATES EXCEEDING 99% OR REACHING
100% WITH THE .5 ML DOSE. VERY GOOD RESPONSE.
AT MONTH SEVEN WE SEE THAT. BECAUSE OF THE PRE-EXISTING
IMMUNITY, WE ALSO LOOKED AT THE RATE OF SUBJECTS WHO WOULD
ACHIEVE ZERO CONVERSION. IN AT LEAST FOUR-FOLD INCREASE.
WITH .25 ML THIS RATE WAS EXCEEDING 96% ON DAY 56 AND IT
WAS ALSO AROUND ABOUT 85% WITH THE FULL DOSE.
LOOKING AT GEOMETRICS, WITH THE TWO DOSES, IN THE CHILDREN AGE 2
TO BELOW 3 YEARS WAS .25 ML DOSE, GMT WAS 288 AND THE OLDER
AGE GROUP WITH THE FULL DOSE OF VACCINE ACHIEVED A GMT OF AROUND
ABOUT 200. AGAIN, WE SEE AS WE FOLLOW THE
CHILDREN THROUGH TO MONTH 7 THAT THE GEOMETRIC MEANS DECLINE AS
EXPECTED. NOW MOVING OVER TO PRESENT THE
SAFETY DATA OFF THE VACCINE AND THE WAY THE NEXT COUPLE OF
SLIDES ARE DEFINED IS THAT I WILL FIRST SHOW YOU THE ADULTS
FOR CHILDREN AGE FROM 2 MONTHS TO BELOW 1 YEAR COMPARED TO
PREDMAR, FOLLOWED BY THE SAME DATA FOR THE AGE GROUP THROUGH
17 YEARS OF AGE. THE PRIMARY END POINT OF THE
STUDY WAS THE RATE OF SUBJECTS WAS ANY SERIES OR MEDICALLY
ATTENDED EVENTS. RATES WAS VERY WELL COMPARABLE.
TWO VACCINES AROUND 3 4 40%. ACTUALLY THERE WAS NO SERIOUS
ADVERSE EVENT. THESE ARE THE SAME DATA UP TO 18
YEARS. PRIMARY END POINT IS VERY WELL
COMPARABLE BETWEEN THE TWO VACCINE GROUPS.
WE DO SEE LESS ADVERSE REACTIONS WITH THE OLDER AGE GROUPS
COMPARED WITH THE INFANTS. SO 16% AND 14% OF CHILDREN HAD
ANY SERIOUS OR MEDICALLY ATTENDED ADVERSE EVENTS UP TO
DAY 56. AGAIN THERE IS NO DEFENSE IN
ADVERSE EVENT RATES OVERALL FOR THE TWO STUDIES.
AROUND ABOUT 60% OF CHILDREN HAD ANY ADVERSE EVENT DURING THE
TRIALS. THE RATES ALSO WELL COMPARABLE
IF YOU LOOK AT MEDICALLY ATTENDED OR SERIOUS ADVERSE
EVENTS ON THEIR OWN. THIS IS THE DATA FOR THE
COMPLETE FOLLOW-UP UP TO MONTH SEVEN OF THE STUDY.
LONG-TERM DATA. AGAIN WE SEE VIRTUALLY NO
DIFFERENCE IN END RATES BETWEEN THOSE RECEIVING THE PREDMAR.
THESE ARE THE SAME DATA FOR THE AGE GROUP 1 TO BELOW 18 YEARS OF
ABLE. AGAIN, NO BIG DIFFERENCES OR NO
PRONOUNCED DIFFERENCES BETWEEN THE CHILDREN FOR ANY ADVERSE
EVENDZ, MEDICALLY ATTENDED OR SERIOUS ADVERSE EVENTS.
THERE WAS UNFORTUNATELY ONE DEATH DURING THE STUDY.
A 12-YEAR-OLD BOY WHO DIED FOLLOWING SUSPECTED MENINGITIS
AND FEW PNEUMONIA AND THE UNDERLYING CAUSE OF DEATH WAS
BELIEVED TO BE DISSEMINATED INTERMUSCULAR COAGULATION.
THIS WAS REVIEWED BY INDEPENDENT DATA AND SAFETY MONITORING BOARD
WHO CONCLUDED THAT IT IS VERY UNLIKELY THAT THIS WOULD HAVE
ANYTHING TO DO WITH VACCINATION. NOW MOVE OVER TO SHOW YOU YOU
THE SOLICITED ADVERSE EVENTS. FIRST STARTING WITH REACTIONS,
LOCAL REACTIONS IN CHILDREN BELOW 1 YEAR OF AGE.
IF WE LOOK AT THE RESULTS OF DOSE ONE, CAN YOU SEE THAT 19%
OF CHILDREN HAD HAD ANY ADVERSE -- ANY LOCAL REACTION
WITH THE FIRST DOSE COMPARED TO 32% FOR PREDMAR.
THE RATES FOR LOCAL REACTIONS ARE LOWER FOR REDNESS,
TENDERNESS, SWELLING AND HARDENING COMPARED TO THE
PREDMAR. AS WE'VE SEEN IN THE OTHER
STUDIES, WE SEE FEWER LOCAL REACTIONS WITH THE SECOND DOSE
OF VACCINE. 8% OF CHILDREN HAD ANY LOCAL
REACTION WITHIN SEVEN DAYS UNTIL THE SECOND DOSE COMPARED TO 18
FOR PREDMAR. LOOKING AT THE DATA FOR OLDER
AGE GROUPS, ABOUT 14% IN BOTH GROUPS HAD ANY LOCAL REACTION
WITHIN SEVEN DAYS AFTER THE FIRST DOSE AND NONE OF THE
SOLICITED LOCAL REACTIONS OCCURRED IN GREATER THAN 10% OF
SUBJECTS OVERALL. AGAIN, WE SEE THAT WITH SECOND
DOSE, THE LOCAL ADVERSE EVENTS DECLINED DOWN TO ABOUT 6% WHO
HAD ANY INJECTION SITE REACTION. WE DON'T HAVE THESE FOLLOW-UP
DATA FOR THE SECOND DOSE. NOW MOVING TO THE SOLICITED
REACTIONS, AGAIN WITHIN SEVEN DAYS AFTER EACH OF THE
VACCINATIONS, OVERALL ABOUT 40% OF CHILDREN HAD ANY SOLICITED
REACTION WITHIN SEVEN DAYS OF THE FIRST DOSE.
THE DOMINATING EFFECT WAS FEVER AROUND 24%, 25%.
HOWEVER, THE FEVER WAS MOSTLY VERY MILD.
WE SEE HERE THAT ONLY AFTER THE SECOND DOSE WE HAVE ONE CHILD
WITH FEVER GREATER THAN 39.4 DEGREES CENTIGRADE.
OTHER REACTIONS THAT OCCURRED IN MORE THAN 10% OF THE STUDY
PARTICIPANTS WERE IRABILITY ARI AND DIARRHEA.
ALL OTHER REACTIONS WERE LESS COMMON.
REACTION TO THE SECOND DOSE OCCUR AT A LOWER FREQUENCY.
THESE ARE REALLY RESPECTED DATA FOR AGE GROUP 1 TO BELOW 18
YEARS OF AGE. AGAIN WE SEE COMPARABLE RATE OF
SYSTEMIC REACTIONS TO THE FIRST DOSE AND FEVER AS THE ONLY
SYMPTOM THAT OCCURS IN MORE THAN 10% OF THE CHILDREN AND AGAIN,
FEVER IS MOSTLY OF MILD NATURE WITH VERY FEW CHILDREN HAVING
HIGHER GRADE FEVERS. NOW I'D LIKE TO MOVE OVER TO
LOOK AT THE SERIOUS ADVERSE EVENTS IN MORE DETAIL.
AGAIN FIRST LOOKING AT INFANTS THROUGH TO ONE YEAR OF AGE, UP
TO DAY 56 WE DID NOT HAVE A SERIOUS ADVERSE EVENT IN THE
FIXED GROUP. THERE WAS ONE ADVERSE EVENT IN
THE PREDMAR GROUP, A CONVNVULSI. THE RESPECTIVE DATA FOR THE
OLDER AGE GROUP, IF YOU LOOK AT THE SUBJECTS WITH ANY SERIOUS
ADVERSE EVENTS, UP TO DATE, 56 ON ONE GROUP COMPARED TO THE
OTHER GROUP. THESE ARE SIX SUBJECTS AND FOUR
SUBJECTS. A RELATIVELY COMPARABLE RATE.
THE MOST COMMONLY SEEN SERIOUSLY ADVERSE EVENTS ARE ACTUALLY
BELONGING TO THE GROUPS OF INFECTIOUS DISEASES.
AS YOU CAN SEE HERE, NONE OF THESE ASEs OCCUR IN MORE THAN
ONE SUBJECT AND IF WE LOOK AT NON-EFFECTS OF THE SERIOUS
ADVERSE EVENTS, THE REACTION WE'VE SEEN MORE COMMONLY WAS
CONVULSIONS. I'LL HAVE MORE ON THAT IN A
MOMENT. THIS HERE LOOKS AT THE RATE OF
SEIZURES SPECIFICALLY IN THE CHILDREN AGED BETWEEN 2 MONTHS
AND THROUGH 2 YEARS OF AGE. IF WE LOOK AT OVERALL RATES
HERE, IT IS 1% OF 8 OF 771 CHILDREN IN THIS AGE RANGE.
1.6% IN THE CHILDREN WHO RECEIVED PREDMAR AND 1.4% IN THE
CHILDREN WHO HAVE RECEIVED ANOTHER.
I WOULD LIKE TO REMIND YOU OF THE RANDOMIZATION RATIO.
WE HAD THE STUDY, OVERALL 3-1. WE EXPECT TO SEE MORE CASES HERE
COMPARING TO THE CONTROL VAC SEEBS BUT THE CENTRAL
DISTRIBUTION HERE DID NOT INDICATE THERE WOULD BE ANY
CLUSTERING AFTER VACCINATION XERO.
BECAUSE OF THE PREVIOUSLY USED JE-VC VACCINE RELATED TO
HYPERSENSITIVITY REACTION, WE SPECIFICALLY LOOKED AT THE RATES
OF ADVERSE EVENTS LIKE HYPERSENSITIVITY OR REACTIONS
THAT OCCURRED WITHIN 14 DAYS AFTER VACCINATION.
THIS SLIDE SUMMARIZES THIS DAY THAT.
WE HAD A TOTE FL NIAL OF NINE S WHO HAD ANY REACTION.
ALL OF THESE OCCURRED IN CHILDREN WHO RECEIVED THE .25 ML
DOSE. IN THE SAME TIME FRAME, WE'VE
HAD ONE SUBJECT IN THE GROUP WITH REACTION AFTER 14 DAYS OF
VACCINATI VACCINATION.
WHILE THIS MAY APPEAR AS A DIFFERENCE, I WOULD ACTUALLY
LIKE TO REMIND EVERYBODY THAT I'VE SHOWED YOU BEFORE, DUE TO
THE DIFFERENT NUMBER OF DOSES THAT WAS ADMINISTERED THROUGHOUT
THE TRIAL, WE HAVE A MUCH HIGHER ACCUMULATED VACCINATION
FOLLOW-UP TIME HERE FOR XERO THAN FOR THE TWO OTHER VACCINES.
JUST KEEP THAT IN MIND WHEN LOOKING AT THE OVERALL RATE OF
SUCH EVENTS. IF WE LOOK AT THE REACTIONS IN
DETAIL, ACTUALLY THERE WERE THREE CASES OF JUST RASH THAT
OCCURRED WITHIN THIS 14 DAYS WINDOW.
ACTUALLY ALL OF THESE THREE CASES OCCURRED BETWEEN SEVEN AND
TEN DAYS AFTER THE FIRST DOSE VACCINE.
THE CHILDREN WERE ALL GIVEN A SECOND DOSE OF VACCINE AND NONE
OF THEM HAD A REACTION TO THIS SECOND DOSE OF VACCINATION.
THERE WERE ALSO TWO OTHER CASES OF RASH WHERE THE RASH WAS
BELIEVED TO BE ASSOCIATED WITH A PROBABLE VIRAL INFECTION.
CHILD HAD A FEVER AT THE SAME TIME.
THERE WERE TWO CASES OF HYPERSENSITIVITY.
ONE CHILD WHO RECEIVED THE HYPERSENSITIVITY SEVEN DAYS
AFTER THE SECOND DOSE, THAT REACTION WATT WAS BASICALLY NOT
ASSOCIATED WITH ANY SYSTEMIC SYMPTOMS, SO LIMITED TO ITCHING
AND NOTHING THAT WOULD REQUIRE ANY MEDICAL TREATMENT.
SECOND CASE OF HYPERSENSITIVITY -- THE CHILD
RECEIVED THE SECOND DOSE AND DID NOT HAVE ANY REACTION
SUBSEQUENT. THERE WERE ALSO TWO REACTIONS.
ONE FIVE DAYS AFTER THE FIRST DOSE WHERE THE CHILD WAS GIVEN
THE SECOND DOSE AND DID ALSO NOT HAVE A REACTION TO THIS SECOND
DOSE. THEN FINALLY ONE REACTION 13
DAYS AFTER THE FIRST DOSE. THIS CHILD WAS NOT GIVEN THE
SECOND DOSE OF THE VACCINE BUT NEN HERE THE INVESTIGATOR
BELIEVES THAT THE UNDERLYING REASON FOR THIS WAS MOST LIKELY
A VIRAL INFECTION. WITH THID'S LIS I'D LIKE TO SUM
AND PRESENT OUR CONCLUSIONS. OVERALL THE SAFETY PROGRAM OF
XECHLT RO IN CHILDREN WAS COMPARABLE TO THE CONTROL
VACCINES. THE MOST COMMONLY OBSERVED
ADVERSE EVENTS WERE IN LINE WITH THE EXPECTED ADVERSE EVENTS
PROFILED IN THE PDR GROUP POPULATION AND MOST OF THE
ADVERSE EVENTS WERE OF MILD NATURE.
I HAVEN'T SHOWN YOU THE DATA SEPARATELY, BUT ESPECIALLY IN
THE AGE GROUP 12 TO BELOW 18 YEARS, THE PROFILE RESEMBLED THE
ADVERSE EVENT PROFILE. COMPARED TO PREDMAR, XERO
APPEARED TO CAUSE FEWER LOCAL REACTIONS.
IT WAS IMMUNO GENIC AND ALL GROUPS TESTED AND BOTH TESTS --
THE ZERO PROTECTION RATE AT DAY 66 WAS 99% TO 100%.
THE MONTH SEVEN RANGED BETWEEN 85% AND 100%.
AGAIN WHILE I DIDN'T SHOW YOU THE DATA SPECIFICALLY IN THE AGE
GROUP 12 TO 18 YEARS, IT IS COMPARABLE TO WHAT WE SEE IN
ADULTS. SO WITH THAT, I'D LIKE THAT TONK
YOU FOR YOUR ATTENTION. I'M HAPPY TO TAKE ANY QUESTIONS.
>> THANK YOU. LET'S OPEN IT UP FOR ANY
QUESTIONS. >> I HAVE TWO RELATED QUESTIONS.
CAN YOU DESCRIBE THE EFFECTIVE AGE AND PRIOR -- PRE-EXISTING
IMMUNITY ON A RESPONSE TO THE VACCINE AND, ALSO DESCRIBE IN
TERMS OF PERSISTENCE OF ANTIBODY IF THEY HAD PRE-EXISTING AEBT
NODDI NODDI
ANTIBODIES. >> YOUR QUESTION IS IMMUNOGENIC.
I'M GOING TO PULL UP THE DATA BY AGE GROUPS.
BASICALLY THIS SLIDE SHOWS YOU ZERO PROTECTION RATES BROKEN
DOWN BY AGE. AS YOU CAN SEE, THE RESULTS HERE
ON DAY 56, WE HAVE A VERY GOOD 100% PROTECTION RATE THROUGHOUT
THE AGE GROUPS WE HAVE BEEN STUDYING.
6 MONTHS, 6 TO 12 MONTHS, WE HAVE 99% IN THE AGE GROUP 1 TO 3
YEARS, THEN 3 TO 12, 12 TO 18 AGAIN ARE UP AT 100%.
WE HAVE A VERY GOOD PERSISTENCE WITH THE YOUNGEST AGE GROUPS
HERE AT MONTH SEVEN. 100% PROTECTION.
STILL WITH THE CHILDREN BELOW 12 MONTHS.
THE 1 TO 3-YEAR AGE GROUP WE SEE 85% PROTECTION AT MONTH SEVEN,
AND THEN PERSISTENCE AGAIN APPEARS TO BE LITTLE BIT HIGHER
WITH THE OLDER AGE GROUPS. THE RESPECTIVE GEOMETRIC MA
ACTUALLY RECEIVE THE BEST RESPONSE IN THE YOUNGEST AGE
GROUPS. CHILDREN 6 TO 12 MONTHS OF AGE.
ALTHOUGH WE USED A HALF DOZEN OF OTHER AGE GROUPS.
WE SEE PERSISTENCE IS BETTER IN THE EXTREMES OF THE AGE GROUPS.
THE VERY YOUNG CHILDREN TEND TO KEEP HIGHER GMTs.
THEN WE SEE AGAIN HIGHER GMTs IN THE OLDER AGE GROUPS.
THAT LEADS OVER TO THE -- BASICALLY LOOKING AT THE IMPACT
OF BASELINE GMT. LET ME WALK YOU THROUGH THAT
SLIDE. IT IS A LITTLE COMPLEX.
OVERALL, WHAT THIS COMPARES IS THE GMTs IN CHILDREN WHO WERE
POSITIVE FOR JEV, A BASELINE THAT
THAT'S 70 COMPARED TO 79. WE SEE THAT ON DAY 56 WE GET
LOWER GMTs COMPARED TO THE .5 ML DOSE.
LOOKING AT THE MONTH SEVEN DATA, IT APPEARS THAT THOSE WHO ARE
POSITIVE AT BASELINE RETAIN HIGHER GMPs COMPARED TO THOSE
WHO ARE NEGATIVE OF BASELINE. >> DR. HARRISON.
WAS THERE ANY EFFORT TO BLIND THE INDIVIDUALS COLLECTING THE
ADVERSE EVENT TERMS OF VACCINATION STATUS?
>> NO. WE HAVE CONDUCTED THE STUDY AS
AN OPEN LABEL SO THE SAFETY DATA COLLECTION AND MOST OF THE
IMMUNOGENICITY DATA WAS COLLECT. THE DIFFERENT NUMBER OF
VACCINATIONS THAT WERE GIVEN IN THE STUDY WE WANTED TO HAVE
UTILIZED PLACEBO SHOTS JUST FOR THE PURPOSE OF BLINDING.
WE DIDN'T CONSIDER IT JUSTIFIED BASED ON THE FACT THAT WE HAD
VE VERY ROBUST POINTS.
>> COULD YOU SAY SOMETHING ABOUT HOW THE VACCINE IS SUPPLIED BOTH
AT .25 AND THE .5 DOSE? >> SO THE VACCINE SUPPLY WILL BE
SIMILAR PRESENTATION GOING FORWARD.
THE VACCINE IS -- I WOULD SAY A VERY NICHE PRODUCT FOR THE AGE
GROUPS BELOW 3 YEARS. THAT'S PRACTICALLY NOT ROUTINELY
GIVEN AT THAT AGE GROUP. SO THE LABEL IN THE FUTURE WILL
CARRY A MARK AND THERE WILL BE A PROCEDURE TO EXPEL VOLUME UP TO
THAT MARK AND INJECT THE REMAINING VOLUME AT THE .25 ML
DOSE IN CHILDREN BELOW 3 YEARS. >> MY QUESTION RELATES TO THE
MEDICALLY ATTENDED ADVERSE EVENTS, ALTHOUGH I CERTAINLY SEE
THAT THE RATES WERE SIMILAR IN T THE XERO GROUP COMPARED TO BOTH
CONTROLS. I'M SURPRISED AT HOW HIGH THEY
ARE. FOR EXAMPLE, IN 1 TO 18
YEAR-OLDS, YOU HAD A 25% MEDICALLY ATTENDED ADVERSE
EVENT. THAT'S A VACCINE THAT GENERALLY
HAS VERY LITTLE SIDE EFFECTS. IS THIS IN A WAY AN ARTIFACT OF
INSTRUCTIONS GIVEN TO PATIENTS WHEN THEY SHOULD SEEK MEDICAL
CARE OR IS THIS ROUTINE PRACTICE IN THE
PHILIPPINES OR CAN YOU COMMENT FURTHER ON WHAT TYPES OF EVENTS
LED TO MEDICALLY ATTENDED -- >> SO WE BELIEVE THIS IS A
RESULT OF THE SITUATION THAT WE ARE APPARENTLY GOING TO A
RESOURCE LIMITED COUNTRY AND ARE OFFERING FREE MEDICAL CARE FOR
THE STUDY PERSISTENCE. THEY'RE PROBABLY MORE LIKELY TO
SEE A DOCTOR IF THEY HAVE ANY ADVERSE EVENTS.
THE MAJORITY OF THE UNSOLICITED ADVERSE EVENTS THAT WERE
OBSERVED IN THE STUDY ARE INFECTIOUS DISEASES AND THAT'S
CERTAINLY ALSO TRUE FOR THE MEDICALLY ATTENDED ADVERSE
EVENTS. THESE ARE CASES OF ENTERITIS.
WE'VE HAD CHILDREN SEEKING MEDICAL ATTENTION FOR THINGS
LIKE DOG BITES, NEEDING RABIES SHOTS.
>> ANY OTHER QUESTIONS? SEEING NONE, WHY DON'T WE HAVE
DR. FISCHER COME ON UP. >> GOOD MORNING.
>> SO ON BEHALF OF THE JE-VC VACCINE WORK GROUP, I'M GOING TO
PRESENT THE GRADE EVIDENCE AND THE PROPOSED RECOMMENDATIONS FOR
THE APPROVE USE IN CHILDREN. JUST TO REVIEW, IN MARCH 2009
JE-VC WAS LICENSED FOR USE IN ADULTS IN THE UNITED STATES,
EUROPE AND AUSTRALIA, AND IN JUNE OF THAT SAME YEAR, ACIP
APPROVED THE CURRENT RECOMMENDATIONS FOR THE USE OF
JE-VC VACCINE IN TRAVELERS. THOSE RECOMMENDATIONS INCLUDED
JE-VC FOR ADULTS 17 YEARS OF AGE OR OLDER, AND THE INACTIVATED
MOUSE BRAIN DERIVED JD VACCINE FOR ADULTS IN CHILDREN 1 YEAR OF
AGE OR OLDER. AS WE'VE HEARD, JE-MB IS NO
LONGER PRODUCED AND NO JE VACCINE HAS BEEN LICENSED OR
AVAILABLE FOR CHILDREN IN THE U.S. IN THE PAST TWO YEARS.
LAST MONTH JE-VC WAS LICENSED FOR CHILDREN 2 MONTHS OF AGE OR
OLDER. WORK GROUP EVALUATED THE
EVIDENCE JE-VC IN CHILDREN USING THE GRADING OF
RECOMMENDATIONS, ASSESSMENT, DEVELOPMENT AND EVALUATION, OR
AS WE'VE COME TO KNOW IT, GRADE METHOD.
WE'VE DEVELOPED A POLICY QUESTION, IDENTIFIED OUTCOMES OF
CRITICAL IMPORTANCE, PERFORMED A SYSTEMATIC REVIEW OF PUBLISHED
AND UNPUBLISHED DATA AND EVALUATED EVIDENCE OF BENEFITS,
HARMS, VALUES AND COSTS BEFORE FORMULATING RECOMMENDATIONS FOR
USE OF JE-VC IN CHILDREN. THE POLICY QUESTION CONSIDERED
BY THE WORK GROUP WAS AS FOLLOWS.
SHOULD JE-VC BE RECOMMENDED FOR USE IN CHILDREN 2 MONTHS THROUGH
16 YEARS OF AGE AT INCREASED RISK OF TRAVEL RELATED
VACCINES -- TRAVEL RELATED ARE EXPOSURE TO JE VIRUS.
THE POPULATION INCLUDES CHILDREN 2 MONTHS THROUGH 16 YEARS OF
AGE, TRAVELING TO JE-ENDEMIC AREAS.
PROPOSED INTERVENTION IS JE-VC ADMINISTERED IN A TWO-DOSE
PRIMARY SERIES. AND AS MENTIONED, NO JE-VC -- NO
JE VACCINE IS CURRENTLY RECOMMENDED AND AVAILABLE FOR
USE IN CHILDREN. SURVEYED THE W TO IDENTIFY AND RANK THE OUTCOME
MEASURES TO BE EVALUATED. AS THIS SLIDE SHOWS, THE WORK
GROUP IDENTIFIED VACCINE EFFICACY AND ZERO PROTECTION AT
1 AND 6 MONTHS AS BENEFITS OF CRITICAL IMPORTANCE.
THERE ARE NO EFFICACY DATA FOR JE-VC.
A PLAQUE REDUCTION NEUTRALIZATION TEST IS AN
ESTABLISHED IMMUNOLOGIC PROTECTION.HARMS CONSIDERED,
CRITICAL OUTCOMES WERE SERIOUS ADVERSE EVENTS AND SYSTEMIC
ADVERSE EVENTS. THE FDA DEFINITION FOR SERIOUS
ADVERSE EVENTS WAS USED. SYSTEMIC ADVERSE EVANTS
EVALUATED INCLUDED FEVER, RASH, HYPERSENSITIVITY, NEUROLOGIC
ADVERSE EVENTS AND MEDICALLY ATTENDED ADVERSE EVENTS.
INJECTION SITE REACTIONS AND INTERFERENCE WITH OTHER VACCINES
WERE CONSIDERED IMPORTANT OUTCOMES BUT WERE NOT INCLUDED
IN THAT GRADE EVALUATION. TO THE
GRADE EVALUATION WE PERFORMED A SYSTEMATIC SEARCH AND
REVIEW OF THE PUBLISHED LITERATURE.
WE IDENTIFIED 12 STUDIES THAT REPORTED PRIMARY DATA RELATIVE
TO THE CRITICAL OUTCOME MEASURES INCLUDING THE ONE STUDY IN
CHILDREN THAT'S PUB ACCOMPLISHED AND 11 STUDIES IN RESULTS.LISHE1
STUDIES IN RESULTS. WE REVIEWED TWO CLINICAL TRIALS
THAT WERE UNPUBLISHED. THEIR REPORTS FOR JE-VC
ADMINISTERED TO ADULTS IN THE UNITED STATES OR U.S. MILITARY
PERSONNEL AND TWO CLINICAL TRIALS OF SIMILAR INACTIVATED
JE-VC VACCINE LICENSED IN INDIA. I WILL SUMMARIZE THE RELEVANT
EVIDENCE FOR EACH OF THE CRITICAL OUTCOMES.
THE EVIDENCE USED TO EVALUATE ZERO PROTECTION AT ONE MONTH
AFTER VACCINATION WITH JE-VC WAS FROM TEN STUDIES INCLUDING THREE
IN CHILDREN, SEVEN IN ADULTS. INCLUDING RANDOMIZED CONTROL
TRIAL IN CHILDREN 1 AND 2 YEARS OF AGE IN INDIA, RANDOMIZED
CONTROL TRIAL IN CHILDREN 2 MONTHS THROUGH 17 YEARS OF AGE
IN PHILIPPINES, AND THEN OBJECTIOHHAL
STUDY IN CHILDREN 2 MONTHS TO 17 YEARS OF AGE IN THE U.S., EUROPE
AND AUSTRALIA. THE STUDY IN THE PHILIPPINES
PROVIDED MORE COMPARATIVE IMMUNOGENICITY DATA SO FOR THIS
PART OF THE EVALUATION WOULD CONSIDER IT OBSERVATIONAL.
FOR THE 578 CHILDREN WHO RECEIVED JE-VC IN THE THREE
STUDIES COMBINED, WERE ZERO PROTECTED AT ONE MONTH AFTER THE
TWO-DOSES. OF THE SEVEN STUDIES IN ADULTS
WITH ZERO PROTECTIONON DATA AT E MONTH, FIVE WERE RANDOMIZED
CONTROLLED TRIALS AND TWO OBSERVATIONAL STUDIES.
TWO OF THE RANDOMIZED TRIALS HAD NO COMPARATIVE IMMUNOGENICITY
DATA AND WERE CONSIDERED OBJECTIVE STUDIES.
AN INACTIVATED MOUSE BRAIN VACCINE FROM KOREA, ONE FROM
JAPAN AND THE JE-VC VACCINE FROM INDIA.
OF THE 800 RECIPIENTS IN THE SEVEN STUDIES COMBINED, 98% WERE
ZERO PROTECTED AT ONE MONTH AFTER TWO-DOSE PRIMARY SERIEDE
A WEIGHTED RANDOM EFFECTS MODEL CAMPAIGNING DATA FROM THE FOUR
RANDOMIZED CONTROL TRIALS IN BOTH CHILDREN AND ADULTS.
THE PROPORTION OF SUBJECTS AND NEUTRALIZING ANTIBODIES ARE
REPEATED FROM THE PREVIOUS SLIDE.
RISK RATIOS AT 95% CONFIDENCE INTERVALS ARE CALCULATED TO
COMPARE ZERO PROTECTION RATES IN JE-VC AND THE COMPARATIVE JE
VACCINE RECIPIENTS. RISK RATIOS FROM INDIVIDUAL
CLINICAL TRIALSAND COMBINED TO PROVIDE AN OVERALL
COMPARISON FROM THE FOUR STUDIES STRATIFIED BY CHILDREN AND
ADULTS. THE RISK RATIOS AND CONFIDENCE
INTERVALS ARE PLOTTED ON THE RIGHT.
THE BLUE SQUARES AND BLACK LINES DISPLAY RESULTS IN A SINGLE
STUDY. THE BLA IS THE DISPLAYED
COMBINED RESULTS FOR CHILDREN, ADULTS, THEN OVERALL.
IN THIS FIGURE, RESULTS TO THE RIGHT OF THE VERTICAL LINE
FAVORS ZERO PROTECTION IN JE-VC RECIPIENTS, RESULTS TO THE LEFT
OF THE VERTICAL LINE FAVOR ZERO PROTECTION RATES FOR PEOPLE WHO
RECEIVED COMPARATIVE VACCINES. OVERALL THERE WAS NO DIFFERENCE
IN ZERO PROTECTION RATES AT ONE MONTH BETWEEN JE-VC AN THE OTHER
JE VACCINES. MOVING ON TO 5 TO 6 MONTHS, THE
EVIDENCE USED TO EVALUATE AFTER THAT WAS FROM FOUR STUDIES,
INCLUDING TWO EACH IN CHILDREN AND ADULTS.
FOR THE PEDIATRIC STUDIES, FOLLOW-UP WAS AT SIX MONTHS
AFTER COMPLETING THE TWO-DOSE PRIMARY SERIES.
FOR THE STUDIES IN ADULTS, FOLLOW-UP WAS AT 5 MONTHS AFTER
COMPLETING THE TWO-DOSE SERIES OR SIX MONTHS AFTER THE FIRST
DOSE. OF THE 800 JE-VC RECIPIENTS IN
THE FOUR STUDIES COMBINED, 90% STILL HAD PRNT TIGHTER OF 10 OR
GREATER FIVE TO SIX MONTHS AFTER THE TWO-DOSE PRIMARY SERIES.
THIS INCLUDED 89% OF 500 CHILDREN AND 80% OF 527 ADULTS.
FINDINGS FROM THE ONE RANDOMIZED CONTROL TRIAL IN ADULTS SHOWED
THAT A SIGNIFICANTLY HIGHER PROPORTION OF JE-VC RECIPIENTS
WERE ZERO PROTECTED AT FIVE MONTHS, FOLLOWING VACCINATION,
COMPARED TO SUBJECTS RECEIVING THE MOUSE BRAINED DERIVED JV
VACCINE. EVIDENCE USED TO OVAL WAEVALUAT
SERIOUS ADVERSE EVENTS WAS FROM 13 STUDIES, INCLUDING 11
CLINICAL OR OBSERVATIONAL STUDIES IN CHILDREN OR ADULTS
AND TWO REVIEWS OF MOST MARKETING SURVEILLANCE DATA IN
ADULTS. THIS TABLE SUMMARIZES THE DATA
FROM THE THREE PEDIATRIC STUDIES.
AS PREVIOUSLY PRESENTED, THE CONTROL VACCINE FOR THE STUDY IN
INDIA WAS AN INACTIVATED MOUSE-BRAIN DERIVED VACCINE FROM
KOREA. THE CONTROL VACCINES IN THE
PHILIPPINES STUDY WERE HEPATITIS A APNEUMKNEW O.
NO STUDIES WERE REPORTED IN INDIA OR FROM CHILDREN IN NONE
ENDIMMIC COUNTRIES. SIX SERIOUS ADVERSE EFFECTS WERE
REPORTED FROM THE 1,111 CHILDREN FROM THE PHILIPPINE STUDY.
THESE INCLUDED TWO SEIZURES AN ONE REPORT OF CELLULITICELLULIT
GASTROENTERITIS AND DENGUE. IN THE SEVEN CLINICAL TRIALS IN
ADULTS, SERIOUS ADVERSE EVENTS WERE REPORTED IN LESS THAN 1%
WITHIN 56 DAYS AFTER THE FIRST DOSE.
THE CONTROL VACCINES IN THE VARIOUS STUDIES INCLUDED MOUSE
BRAIN DERIVED JE VACCINE FROM JAPAN AND INDIA.
HEPATITIS A VAC TEEN CINE AS WEA PLACEBO.
THIS FIGURE SHOWS THE WEIGHTED RANDOM EFFECTS MODEL COMBINING
DATA FROM THE SEVEN RANDOMIZED CONTROL TRIALS IN BOTH CHILDREN
AND RESULTS. THE RESULTS NOW TO THE LEFT OF
THE VERTICAL LINE INDICATE FEWER ADVERSE EVENTS IN JE-VC
RECIPIENTS. RESULTS TO THE RIGHT OF THE LINE
INDICATE FEWER EVENTS IN PEOPLE WHO RECEIVED THE CONTROL
VACCINES. OVERALL, THERE WAS NO DIFFERENCE
IN SERIOUS ADVERSE EVENTS REPORTED IN THE 56 DAYS AFTER
THE FIRST DOSE OF JE-VC OR THE COMPARISON VACCINE.
THRE DATA FORSERIOUS ADVERSEHIN SIX FTER THE
FIRST D ORTROLLED IN THE TWO PED STUDIES,
4,471 AFTER THEDOSE.
OF THESE 25 CHILDREN, OR 2% HAD SERIOUS ADVERSE EVENTS REPORTED.
IN A STUDY WHICH POOLED CLINICAL TRIAL DATA FROM ADULTS, 1% OF
3,558 JE-VC SERIOUS ADVERSE EVENTS REPORTED
WITHIN SIX MONTHS AFTER THEIR FIRST DOSE.
AGAIN, THERE WAS NO DIFFERENCE BETWEEN JE-VC AND COMPARISON
VACCINE RECIPIENTS IN SERIOUS ADVERSE EVENTS REPORTED WITHIN
SIX TO SEVEN MONTHS POST VACCINATION IN THE TWO
RANDOMIZED CONTROL TRIALS IN CHILDREN AND ADULTS.
TWO STUDIES EVALUATED SERIOUS ADVERSE EVENTS WERE REPORTED TO
PASSIVE POST MARKETING SURVEILLANCE SYSTEMS FOLLOWING
THE RECEIPT OF JE-VC, ALL IN ADULTS.
THE FIRST IS A PUBLISHED STUDY WHICH INCLUDED REPORTS FROM THE
U.S., EUROPE AND AUSTRALIA FOR APRIL 2009 THROUGH MARCH 2010,
DURING WHICH TIME APPROXIMATELY 250,000 DOSED OF JE-VC WERE
DISTRIBUTED IN THESE AREAS. THE SECOND STUDY INCLUDES
UNPUBLISHED DATA FROM MAY 2009 TO APRIL 2012 WHERE MORE THAN
275,000 DOSED OF JE-VC WERE DRKTED IN THE U.S. ALONE.
APPROXIMATELY 85,000 DOSED DISTRIBUTED IN THE U.S. FROM MAY
2009 THROUGH MARCH 2010 WOULD BE INCLUDED IN BOTH OF THESE
SURVEILLANCE SYSTEMS. HOWEVER, THERE WAS NO OVERLAP IN
THE 13 SERIOUS ADVERSE EVENTS IDENTIFIED IN THE TWO SEPARATE
ANALYSES. THE RELATIVELY SMALL NUMBER OF
SUBJECTS IN THE CLINICAL TRIALS LIMITED THE ABILITY TO DETECT
RARE SERIOUS ADVERSE EVENTS. HOWEVER, THESE POST MARKETING
SURVEILLANCE DATA FOR MORE THAN 400,000 DOSED DISTRIBUTED
PROVIDES INDIRECT BUT REASSURING DATA IN ADULTS WITH 1.6 TO 3.3
SERIOUS ADVERSE EVENTS REPORTED PER 100,000 DOSES DISTRIBUTED.
THERE WERE NO PATTERNS IN THE TIMING OR TYPES OF SERIOUS
ADVERSE EVENTS THAT WERE IDENTIFIED IN EITHER THE
CLINICAL TRIALS OR TEILLANCE DA. THE EVIDENCE USED TO OVEVALUATE
SYSTEMIC ADVERSE EVENTS FROM VEE YEK WAS FROM NINE STUDIES,
INCLUDING SEVEN CLINICAL TRIALS OR OBSERVATIONAL STUDIES, THEN
THE TWO REVIEWS OF POST MARKETING SURVEILLANCE DATA THAT
I JUST DISCUSSED. THIS SLIDE SHOWS FEVER AS A
SOLICITED EVENT WITHIN SEVEN DAYS AFTER JE-VC.
WHICH WAS REPORTED IN 6% OF 3,659 SUBJECTS IN SIX CLINICAL
TRIALS, INCLUDING 9% OF ABOUT 1,500 CHILDREN, AND 4% OF 2,140
ADULTS. WHEN DATA FROM THE FOUR
RANDOMIZED CONTROL TRIALS WERE COMBINED AND WEIGHTED USING THE
RANDOM EFFECTS MODEL, THERE WAS NO DIFFERENCE IN THE INCIDENCE
OF FEVER BETWEEN RECIPIENTS OF JE-VC OR THE CONTROLLED VACCINE.
RASHES AS SOLICITED ADVERSE EVENT WITHIN SEVEN DAYS OF
EITHER JE-VC DOSE WAS REPORTED IN 2% OF ALL SUBJECTS, INCLUDING
3% OF CHILDREN, 1% OF ADULTS. AGAIN, FOR RASH AND THE
RANDOMIZED CONTROL TRIALS, THERE WAS NO DIFFERENCE IN THE
INCIDENTS BETWEEN JE-VC AND COMPARISON VACCINES.
HYPERSENSITIVITY WITHIN 56 DAYS OF VACCINE WAS
REPORTED IN LESS THAN 1% OF 3,635 JE-VC RECIPIENTS IN THE
FIVE STUDIES COMBINED. IN THE THREE RANDOMIZED CONTROL
TRIALS THERE WAS NO DIFFERENCE AGAIN IN THE INCIDENTS OF
HYPERSENSITIVITY REACTION BETWEEN JE-VC AN CONTROL
RECIPIENTS. NEUROLOGIC ADVERSE EVENTS,
EXCLUDING HEADACHE, WERE REPORTED IN 1% OF JE-VC
RECIPIENTS WITHIN 56 DAYS AFTER THE FIRST DOSE OF VACCINE.
THERE WERE NO CASES OF MENINGITIS, ENCEPHALITIS
REPORTED AMONG JE-VC OR CONTROL RECIPIENTS.
THE FIVE NEUROLOGIC EVENTS REPORTED FOLLOWING JEE JE-VC
INCLUDED THREE SEIZURES IN CHILDREN 1 TO 2 YEARS OF AGE AT
TWO DAYS, EIGHT DAYS AND TWO WEEKS AFTER VACCINATION.
ONE CHILD, 1 TO 2 YEARS OF AGE WHO HAD DROOLING.
ONE CHILD 3 TO 11 YEARS OF AGE WHO HAD DIZZINESS.
THERE WAS NO THE DIFFERENCE BETWEEN JE-VC OR THE
CONTROL VACCINE IN NEUROLOGIC EVENTS.
IN 14% OF TTENDED ADVERSE 3,714 SUBJECTS OVERALL BUT RANGE
FROM 18% IN 1,471 CHILDREN, TO 12% OF 2,243 ADULTS.
WHEN DATA FROM THE THREE RANDOMIZED CONTROL TRIALS WERE
COMBINED AND WEIGHTED IN THE RANDOM EFFECTS MODEL, THERE WAS
NO INCIDENTS IN THE DIFFERENCE OF MEDICALLY ATTENDED ADVERSE
EVENTS BETWEEN JE-VC AND COMPARATIVE VACCINE RECIPIENTS.
IN THE TWO REVIEWS OF POST MARKETING, SURVEILLANCE DATA,
THE REPORTED INCIDENTS OF HYPERSENSITIVITY IN ADULTS WAS
4.5 TO 4.7 PER 100,000 DOSES DISTRIBUTED.
1 HYPERSENS 13 TIVITY REA
OCCURRED AFTER SEVEN DAYS. SIX OCCURRED AFTER
ADMINISTRATION OF JE-VC AND OTHER VACCINES.
FIVE NEUROLOGIC ADVERSE EVENTS FOLLOWING ADMINISTRATION OF
JE-VC IN ADULTS WERE REPORTED FOR TOTAL INCIDENCE OF 1.8 PER
100,000 DOSES DISTRIBUTED. THESE INCLUDED ONE REPORT OF
ENCEPHALITIS AT 39 DAYS AFTER VACCINATION WITH JE-VC AND FOUR
OTHER VACCINES. FOUR REPORTS OF SEIZURES WITHIN
FIVE DAYS AFTER VACCINATION. THREE OF THE JE-VC RECIPIENTS
WITH SEIZURES HAD RECEIVED OTHER VACCINES, AND FOR ONE THERE WAS
NO INFORMATION AVAILABLE. IN ADDITION TO THE STUDIES OF
JE-VC IN CHILDREN AND ADULTS, WE REVIEWED EVIDENCE FOR ZERO
PROTECTION, SERIOUS ADVERSE EVENTS AND SYSTEMIC ADVERSE
EVENTS FROM A RANDOMIZED CONTROL TRIAL AFTER SIMILAR JE VACCINE
WHICH IS MANUFACTURED AND LICENSED IN INDIA UNDER THE
TRADE NAME JEZ. JEZ IS MANUFACTURED BY
BIOLOGICAL E USING TECHNOLOGY TRANSFERRED FROM INTERCELL.
JEZ IS LICENSED IN INTERYA FOR CHILDREN AGE 1 THROUGH 2 YEARS
OF AGE AND ADULTS 18 THROUGH JEZ AND XER USE THE SAME
VERIFICATION STEPS, HOWEVER NO PROCESS COMPARABLE ABILITY
STUDIES HAVE NOT BEEN COMPLETED. IT IS NOT TO BE ASSUMED THE TWO
FINAL VACCINE PRODUCTS ARE THE SAME.
IN ONE RANDOMIZED CONTROL TRIAL COMPARING JEB AND A MOUTH
DERIVED JE VACCINE IN CHILDREN AGE 1 THROUGH 2 YEARS, 92% OF
THE 280 CHILDREN WHO RECEIVED JEV HAD PROTECTED FRU TRALIZING
ANTIBODIES AT ONE MONTH AFTER THE SECOND DOSE.
SERIOUS ADVERSE EVENTS WERE REPORTED IN LESS THAN 1% OF
RECIPIENTS AND FEVER WITHIN SEVEN DAYS AFTER EITHER DOSE WAS
REPORTED IN 11% OF CHILDREN AND RASH IN 1%.
ALTHOUGH JEB AND JE-BC ARE NOT IDENTI
ASSESS THE QUALITY OF EVIDENCE FOR EACH OF THE FOUR CRITICAL
OUTCOMES. WE USED THE STANDARD GRADE
CLASSIFICATIONS WHICH INITIAL EVIDENCE TYPE CLASSIFIED BASED
ON THE STUDY DESIGN, RANDOMIZED CONTROL TRIALS ARE OVERWHELMING
EVIDENCE OF OBSERVATIONAL STUDIES CONSIDERED EVIDENCE TYPE
ONE. RCTs WITH IMPORTANT LIMITATIONS
ARE EXCEPTIONALLY STRONG EVIDENCE FROM OBSERVATIONAL
TRIALS WHERE CLASSIFIED AS EVIDENCE TYPE TWO.
OBSERVATIONAL STUDIES RANDOMIZED CONTROL TRIALS WITH NOTABLE
LIMITATIONS WERE CLASSIFIED AS EVIDENCE TYPE THREE.
AND CLINICAL EXPERIENCE OBSERVATIONAL STUDIES WITH
IMPORTANT LIMITATIONS OR RCTs WITH SEVERAL MAJOR LIMITATIONS
WERE CLASSIFIED AS EVIDENCE TYPE FOUR.
THE EVIDENCE TYPE FOR EACH CRITICAL OUTCOME WAS DECLOOISIG
FOR STUDY DESIGN. ZERO PROTECTION AT ONE MONTH
POST VACCINATION, FOUR RANDOMIZED CONTROL TRIALS
STARTED AT EVIDENCE TYPE ONE BUT WERE DOWNGRADED DUE TO THE
MAJORITY OF THE DATA BEING IN ADULTS FOR A FINAL EVIDENCE TYPE
OF TWO. SHOWN HERE.
THE SIX OBSERVATIONAL STUDIES FOR ZERO PROTECTION AT ONE MONTH
STARTED AT ANNEST TYPE OF THREE AND NO ADDITIONAL SERIOUS
LIMITATIONS WERE IDENTIFIED. ZERO PROTECTION AT SIX MONTHS,
THERE WAS ONE RANDOMIZED CONTROL TRIAL AND THREE OBSERVATIONAL
STUDIES. THE RCT WAS AGAIN DOWNGRADED TO
EVIDENCE TYPE TWO BECAUSE OF INDIRECTNESS AND NO SERIOUS
LIMITATIONS WERE IDENTIFIED IN THE OBSERVATIONAL STUDIES.
OTHER CRITERIA THAT WERE CONSIDERED BUT HAD NO EFFECT ON
EVIDENCE TYPE INCLUDED PUBLICATION BIAS, STRENGTH OF
ASSOCIATION, DOSE RESPONSE AND RESIDUAL CONFOUNDING.
FOR SERIOUS ADVERSE EVENTS, EIGHT RANDOMIZED CONTROL TRIALS
STARTED WITH EVIDENCE TYPE ONE BUT WERE DOWNGRADED BECAUSE OF
BOTH RISK OF BIAS DUE TO INADEQUATE BLINDING AND
DIRECTNESS DUE TO THE MAJORITY OF DATA BEING IN ADULTS FOR A
FINAL EVIDENCE TYPE OF THREE. FIVE OBSERVATIONAL STUDIES
STARTED AT EVIDENCE TYPE THREE AND WERE DOWNGRADED TO EVIDENCE
TYPE FOUR BECAUSE OF INDIRECTNESS.
FOR SYSTEMIC ADVERSE EVENTS, THE EVIDENCE PROVIDED BY FIVE
RANDOMIZED CONTROL TRIALS WERE DOWNGRADED TO TYPE TWO BECAUSE
OF THE RISK OF BIAS, DUE TO INADEQUATE BLINDING.
SIX OBSERVATIONAL STUDIES STARTED EVIDENCE TYPE THREE AND
NO SERIOUS LIMITATIONS WERE IDENTIFIED.
THIS TABLE SHOWS THE OVERALL QUALITY OF EVIDENCE FOR JE-VC IN
CHILDREN. BOTH RCTs AND OBSERVATIONAL
STUDIES WERE CONSIDERED IN THE OVERALL BODY OF EVIDENCE, BUT
THE FINAL EVIDENCE TYPE WAS BASED ON THE RCTs WHICH PROVIDED
THE HIGHER QUALITY OF EVIDENCE. THE OVERALL QUALITY OF EVIDENCE
WAS CLASSIFIED AS TYPE TWO FOR VACCINE SAFETY, AND VACCINE
EFFECTIVENESS USING ZERO PROTECTION AS THE END POINT.
AFTER ESTABLISHING THE QUALITY OF EVIDENCE THE NEXT STEP WAS TO
ASSESS THE VALUES AND PREFERENCES RELATED TO
MANAGEMENT OPTIONS AND OUTCOMES. FOR MOST TRAVELERS TO ASIA, THE
RISK FOR JE IS VERY LOW BUT VARIES BASED ON DESTINATION,
DURATION, SEASON AND ACTIVITIES. MORE THAN 300 CASES OF JE WERE
REPORTED AMONG U.S. MILITARY PERSONNEL DURING THE VIETNAM AND
KOREAN WARS. HOWEVER, FOR THE 40 YEARS FROM
1973 THROUGH 2012, ONLY 65 CASES OF TRAVEL ASSOCIATED JE AMONG
PEOPLE FROM NON-ENDEMIC COUNTRIES HAVE BEEN REPORTED TO
CDC OR PUBLISHED IN LITERATURE. SIX OF THESE CASES OCCURRED IN
CHILDREN. THIS GRAPH SHOWS THE DISEASE ON
SET OF CASES REPORTED FROM 1973 TO 2012.
ADULT CASES ARE SHOWN IN RED AND PEDIATRIC CASES IN YELLOW.
DURING THIS TIME THERE WAS A MEDIAN OF ONE CASE REPORTED PER
YEAR WITH A RANGE OF 6 ZERO TO SIX ANNUAL CASES.
OF THE 65 CASES REPORTED, 26 WERE FATAL AND 43% OF THE
PATIENTS SURVIVED WITH NEUROLOGIC OR COGNITIVE
SEQUELLI. ONE PATIENT HAD AN UNKNOWN
OUTCOME. FOR 47 OF THE 65 TRAVEL
ASSOCIATED CASES, MORE COMPLETE INFORMATION WAS AVAILABLE
REGARDING THEIR ITINERARIES AND ACTIVITIES.
DURATION OF TRAVEL FOR THESE CASES RANGED FROM TEN DAYS TO 34
YEARS AN 64% OF THE CASES WERE TRAVELING FOR A MONTH OR LONGER.
OF THE 17 SHORTER TERM TRAVELERS, 13 HAD A TRIP
DURATION OF TWO TO FOUR WEEKS AND FOUR HAD TRAVELED FOR TEN
DAYS TO TWO WEEKS. AMONG THESE SHORTER-TERM
TRAVELERS, FOUR HAD NO EXTENSIVE RURAL EXPOSURE, TEN TOOK TRIPS
TO RURAL AREAS AND THREE STAYED NEAR COASTAL AREAS.
OF THE 65 REPORTED TRAVEL ASSOCIATED CASES, 19 OCCURRED IN
U.S. TRAVELERS OR EX-PATRIOTS, INCLUDING THREE OF THE PEDIATRIC
CASES. HOWEVER, JE VACCINE HAS BEEN
AVAILABLE IN THE UNITED STATES SINCE 1993 AND IT IS NOT KNOWN
HOW MANY CASES HAVE BEEN PREVENTED DUE TO VACCINATION OR
HOW MANY CASES ARE NOT DIAGNOSED OR REPORTED.
IN ADDITION, NUMBERS OF SUSCEPTIBLE TRAVELERS TO JE
ENDEMIC AREAS IS ALSO UNKNOWN AND THESE LIMITATIONS MAKE IT
DIFFICULT TO ESTIMATE THE OVERALL RISK OF JE AMONG
TRAVELERS TO ASIA. RECOMMENDATIONS REGARDING THE
USE OF JE VACCINES FOR TRAVELERS MUST WEIGH THE RISKS OF TRAVEL
ASSOCIATIONED JE WITH THE BENEFITS OF POTENTIAL RISKS.
OF JE VACCINE. OVERALL RISK OF JE FOR TRAVELERS
IS VERY LOW. WHEN JE DOES OCCUR, HOWEVER, IT
HAS A HIGH MORBIDITY OR MORTALITY AND THERE IS NO
TREATMENT. A SAFE AND EFFECTIVE VACCINE IS
AVAILABLE. THE VACCINE IS RELATIVELY
EXPENSIVE AND THE POSSIBILITY OF RARE SERIOUS ADVERSE EVENTS
CANNOT BE EXCLUDED. FINALLY, BECAUSE HUMANS ARE
NONAMPLIFYING HOSTS, JE VACCINE PROTECTS THE PERSON WHO RECEIVES
IT BUT DOES NOT PREVENT IMPORTATION OR SPREAD OF THE
VIRUS. THE WORK GROUP PLACED A HIGH
VALUE ON PREVENTING A LIFE NOEATMENT OPTIONS.
WE NOTED THAT A SURVEY PERFORMED IN THE UNITED STATES IN 2001
FOUND THAT PARENTS AND COMMUNITY MEMBERS WERE WILLING TO PAY A
MEDIAN OF $500 TO REDUCE THE RISK OF BACTERIAL MENINGITIS
FROM 21 PER 100,000. THOUGH RATES USED IN THE PURR
SAY ARE HIGHER THAN RISKS FOR JE AMONG ALL TRAVELERS TO ASIA,
THESE FINDINGS SUPPORT A WILLING NOSE PAY TO PREVENT THE SERIOUS
OUTCOME.
OUTCOME. THE WORK GROUP ALSO CONSIDERED
THE COST OF JE VACCINE FOR CHILDREN.
SEVERAL STUDIES HAVE DEMONSTRATED THAT USING JE
VACCINE TO IMMUNIZE CHILDREN IN JE ENDEMIC COUNTRIES HAS COST
SAVINGS. HOWEVER GIVEN THE NUMBER OF
TRAVELERS TO ASIA THE LOW RISK OF JE FOR MOST TRAVELERS AND THE
HIGH COST OF JE VACCINES, PROVIDING THE JE VACCINE TO ALL
TRAVELERS TO ASIA WOULD NOT BE COST EFFECTIVE.
IN ADDITION, FOR SOME TRAVELERS EVEN A LOW RISK OF SERIOUS
ADVERSE EVENTS ATTRIBUTABLE TO A VACCINE MIGHT BE HIGHER THAN THE
RISK OF DISEASE. THEREFORE, JE VACCINE SHOULD BE
TARGETED TO TRAVELERS WHO ARE AT INCREASED RISK FOR DISEASE BASED
ON THIS PLANNED ITINERARY AND ACTIVITIES.
THE NUMBER OF U.S. CHILDREN WHO TRAVEL TO ASIA AND HAVE
ITINERARY THAT PUTS THEM AT INCREASED RISK FOR JE IS LIKELY
VERY LOW. IN ADDITION, TRAVEL VACCINES ARE
USUALLY PAID FOR BY THE TRAVELERS THEMSELVES.
THEY ARE NOT COVERED UNDER THE VACCINE FOR CHILDREN'S PROGRAM
OR BY MOST PRIVATE INSURANCE PLANS.
AS A RESULT, THE WORK GROUP DECIDED NOT PERFORM A COST
EFFECTIVENESS STUDY OF JE VACCINE FOR U.S. CHILDREN
TRAVELERS TO JE ENDEMIC COUNTRIES.
THE WORK GROUP CONSIDERED THE FOLLOWING FINDINGS FROM THE
GRADE EVALUATION IN FORMULATING OUR PROPOSED RECOMMENDATIONS.
JE-VC PROVIDES HIGH LEVELS OF ZERO PROTECTION IN CHILDREN
FOLLOWING A TWO-DOSE PRIM SERIES. EVENTS
UNCOMM SIMILAR WITH
VACCINEEMIC ADVERSE EVEN OCCUR AT RATES SIMILAR TO
COMPARISON VACCINES. THERE WAS A HI PLACED ON
PREVENTION OF A SERIOUS DISEASE WITH NO TREATMENT AND
SUBSTANTIAL MORBIDITY AND MORTALITY.
HOWEVER, THE OVERALL LOW RISK OF DISEASE, LOW RISK OF VACCINE
RELATED ADVERSENTS, AND HIGH VACCINE COSTS WARRANT TARGETED
VACCINATIONS OF HIGHER RISK TRAVELERS.
GIVEN THESE CONSIDERATIONS, THE WORK GROUP CAME TO THE FOLLOWING
CONCLUSIONS AND RECOMMENDATIONS -- JE-VC IS
EFFECTIVE USING ZERO PROTECTION AS THE END POINT AND SAFE IN
CHILDREN AGE 2 MONTHS TO 16 YEARS OF AGE WITH AN OVERALL
EVIDENCE TYPE OF TWO. BASED ON THE GRADE EVALUATION
FOR JE-VC, THE WORK GROUP FOUND NO REASONS TO CHANGE THE
EXISTING RECOMMENDATIONS WHICH WERE APPROVED IN 2009.
THEREFORE, THE WORK GROUP PROPOSES TO EXTEND THE CURRENT
ACIP RECOMMENDATIONS FOR USE OF JE-VC TO INCLUDE CHILDREN
GREATER THAN OR EQUAL TO 2 MONTHS OF AGE.
NO OTHER CHANGES TO THE EXISTING RECOMMENDATIONS ARE PROPOSED.
THE RECOMMENDATIONS AND GRADE CATEGORIES THEREFORE ARE AS
FOLLOWS. JE VACCINE IS RECOMMENDED FOR
TRAVELERS WHO PLAN TO SPEND A MONTH OR LONGER IN ENDEMIC AREAS
DURING THE JE VIRUS TRANSMISSION SEASON.
THIS INCLUDES LONG-TERM TRAVELERS, RECURRENT
OR EXPATRIATES WHO WILL BE BASED IN URBAN AREAS BUT ARE LIKELY TO
VISIT ENDEMIC, RURAL OR AGRICULTURAL ARE THE
HIGH-RISK PERIOD OF JE VIRUS TRANSMISSION.
THIS RECOMMENDATION WAS GIVEN A CATEGORYA.
IN ADDITION, VACCINES SHOULD BE CONSIDERED FOR SHORT-TERM
TRAVELERS TO ENDEMIC AREASTHE JN SEASON IF THEY PLAN TO TRAVEL
OUTSIDE OF AN URBAN AREA AND HAVE AN FORVIE VRUS EXPOSURE.
SPENDING TIME OUTDOORS IN RURAL OR AGRICULTURAL AREAS,
PARTICIPATING IN EXTENSIVE OUTDOOR ACTIVITIES, STAYING IN
ACCOMMO CONDITIONING, SCREENS OR BED
NETS. JE VLD BE
CONSIDERED FOR TRAVELERS TO AN AREA WITH AN ONGOING JE
AND TRAVELERS TO ENDEMIC AREAS WHO ARE UNCERTAIN
DESTINATIONS, ACTIVITIES OR DURATION OF TRAVEL.
THIS RECOMMENDATION IS GIVEN A CATEGORY B.
FINALLY, JE VACCINE IS NOT RECOMMENDED FOR SHORT-TERM
TRAVELERS WHOSE VISIT WILL BE RESTRICTED TO URBAN AREAS OR
TIMES OUTSIDE OF A WELL DEFINED JE VIRUS TRANSMISSION SEASON.
AND THIS IS ALSO CATEGORY A. SO FOLLOWING QUESTIONS AND
DISCUSSIONS, WE PROPOSE A ON EXTENDING THE CURRENT ACIP
RECOMMENDATIONS FOR USE OF JE-VC TO INCLUDE CHILDREN 2 MONTHS OF
AGE OR OLDER, THEY WILL NOT BE A VOTE AS DISCUSSED.
WITH THAT, I'D LIKE TO THANK DO BOCCHINI AND DR. RUBEN ANDIN TH
THEIR SUBSTANTIAL TIME AND EFFORTS.
THANK YOU. >> I'D LIKE TO THANK DR. FISCHER
AROUND THE WORK GROUP FOR AN INCREDIBLY CLEAR, BEAUTIFUL
PRESENTATION OF THIS EVIDENCE AND RECOMMENDATION USING
GRADE -- IT ALMOST FELT ROUTINE HERE, YOU BUT IT WAS JUST -- THE
PRESENTATION MAKES IT INCREDIBLY EASY TO FOLLOW AND VERY, VERY
NICELY DONE. >> TWO RELATED QUESTIONS.
DOES YOUR RECOMMENDATION INCLUDE ANY
DOES YOUR RECOMMENDATION INCLUDE ANY ADDITIONAL COMMENTS ABOUT
THE NEED FOR BOOSTER IMMUNIZATION?x
>> SO REGARDING THE FIRST,=#ç TE AREíu
Lw PASSED IN 2011 REGARDING A BOOSTER DOSE FOR
ADULTS WHICH WILL REMAIN IN PLACE.
WE DON'T HAVE DATA AT THIS TIME TO ADDRESS THE BOOSTER DOSE FOR
CHILDREN. AT THIS÷wBrçPOINT, WE'RE ONLY AG
FOR RECOMMENDATIONS FOR THE PRIMARY SERIES.
WE WILL NEED TO ADDRESS THE BOOSTER DOSE FOR CHILDREN.
REGARDING DURATION OF PROTECTION AND ENDEMIC AREAS, IT'S A LITTLE
MORE DIFFICULT TO ANSWER. ONE, BECAUSE THERE ARE, AS WE
HEARD, VARIOUS VACCINES THAT ARE LICENSED AND USED IN ASIA WHICH
ARE DIFFERENT. THEREIN A LIVE ATTENUATED
VACCINE THAT APPEARS TO PROVIDE LONG-TERM PROTECTION.
THE MOST COMMONLY USED VACCINES HAVE BEEN -- DRY VACCINES AND
THOSE HAVE REQUIRED BOOSTER DOSES.
REGARDING THE BUERO CELL VACCINES, THEY HAVEN'T BEEN USED
LONG ENOUGH TO KNOW FULL DURATION OF PROTECTION OR
NUMBERS OF BOOSTER DOSES THAT WOULD BE NEEDED.
>> DR. HARRISON. >> MARC, HOW ABOUT THE
IMMUNIZATION STATUS Ok3RDát TRAVEL RELATED KCCASES?
>> AS FAR AS WE KNOW, FOR THE 65, THOSE ARE ALL REPORTED TO BE
UNVACCINATED. SO THERE'S FAIRLY EXTENSIVE
EVALUATION OF THOSE. >> IS THIS VACCINE RECOMMENDED
FOR CERTAIN CHILD TRAVELERS AND OTHER NONENDEMIC COUNTRIES?
>> YES. SO THE> THANK YOU FOR THE PRESENTATION.
MARC, I'M WONDERING IF YOU CAN EXPAND A LITTLE BIT ON THE
RATIONALE THAT THE WORKING GROUP USED TO DERIVE CATEGORY V
RECOMMENDATION FOR THE SHORT-TERM TRAVELERS.
35% OF THE CASES WERE IN SHORT-TERM TRAVELERS AND I'M
WONDERING A LITTLE BIT MORE ABOUT WHY THAT WOULDN'T BE IN
THE CATEGORY WITH THE SAME STRENGTH OF RECOMMENDATION AS
THE OTHERS. >> RIGHT.
THANK YOU. IF WE COULD GO BACK TO THAT.
SO THIS GOES BACK TO THE DISCUSSION THAT WAS HAD SEVERAL
YEARS AGO WHEN WE DISCUSSED THE VACCINE FOR ADULTS AND, REALLY,
WE CAME TO THE SAME CONCLUSION.( SO TW-THIRDS ESSENTIALLY OF TH
TRAVELERS HAD A LONG DURATION OF TRAVELERS OR EX PATRIOTS.
ONE-THIRD HAD SHORTER TERM TRAVEL.
AMONG THE SHORTER TERM TRAVELERS, THEY ESSENTIALLY HAD
SOME TYPE OF RISK FACTOR IN ALMOST ALL CASE THAT'S YOU CAN
IDENTIFY. SHORTER TRAVELERS ALONE HAD
EXTENSIVE TRAVEL AND THE OTHERS HAD SHORTER TERM TRARL TO RURAL
AREAS. SO WE REALLY THOUGHT IT WAS
IMPORTANT TO PROVIDE THE PEOPLE WHO WERE AT HIGHEST RISK, YOU
KNOW, IT'S NOT IDEAL, BUT BASED ON DURATION OF TRAVEL AND GIVE
SORT OF THE ABILITY FOR THE HEALTH CARE PROVIDERS TO HAVE
INFORMATION THAT THEY CAN ASSESS THE RISK FOR THE LARGEST GROUP
OF TRAVELERS WHO MAY BE SPENDING SHORTER PERIODS OF TIME, BUT
DISTINGUISH THOSE TRAVELERS WHO ARE JUST GOING TO URBAN AREAS
VERSUS RURAL AREAS. SO WE MADE THAT DISTINCTION.
>> SO JUST FOLLOWING UP, IT LOOKS LIKE THE RECOMMENDATION AS
EVEN IF YOU IDENTIFY SHORT-TERM TRAVELERS GOING TO HIGH RISK
AREAS, IT'S STILL A CATEGORY B. >> THAT'S RIGHT.
IT'S A CATEGORY B BECAUSE YOU HAVE TO MAKE THAT
RECOMMENDATION. THAT'S WHAT CATEGORY B IS, IS
THAT THE HEALTH CARE PROVIDER NEEDS TO EVATç+vJ THE PATIENT'S
ITINERARY AND ASSESS THEIR ACTIVITIES TO MAKE THAT
DETERMIN(&F'. SO IT'S NOT RECOMMENDED FOR ALL
PEOPLE WHO ARE SHORTER TERM, THAT THEY CONSIDER THE VACCINE
AND ASSESS WHAT THEIR RISK FACTORS ARE.
>> SO WHY NOT EXPLICITLY STATE IF YOU'RE A SHORT-TERM TRAVELER
GOING TO A HIGH RISK AREA BASED ON THE CRITERIA YOU JUST
BROUGHT, THEY SHOULD BE CATEGORY A?
>> WELL, I THINK THIS DEPENDS HOW MANY GROUPS YOU WANT TO
SPLIT OUT. WE DECIDED TO SPLIT OUT.
THIS DISCUSSION WAS HELD MOSTLY UNDER THE ADULTS AND HELD THE
SAME FOR CHILDREN, SPLIT OUT BASEDED ON THE CLEAREST
IDENTIFIED RISK TO MAKE A RECOMMENDATION FOR ALL OF THOSE
TRAVELERS AND ALLOW HEALTH CARE PROVIDERS TO HAVE THE
CATEGORY B FOR THE OTHER SHORTER TERM
TRAVELERS AND MAKE THAT DETERMINATION BASED ON THEIR
ACTIVITIES.DkL >> OTHER5/ QUESTIONS?
DR. BAKER. >> FOLLOWING UP ON DR. DUCHEN'S
COMMENT, SHOULD BE CONSIDERED IS REALLY DIFFICULT FOR PHYSICIAN
TOES DEAL WITH. SO I DON'T DISAGREE IN ANY WAY
WITH WHERE YOU'VE COMEñ> ANOTHER COMMENT RELATED TO
THE RECOMMENDATIONS THAT I THINK WE PROVIDE SOME CLARITY FOR
PRACTICING PROVIDERS IS DEFINING A NUMBER OF TIMES DURING THE
SEASON. THEY MAY NOT KNOW WHEN GUIDANCE
IS ABOUT THAT SEASON, TIME FRAME WOULD BE HELPFUL.
>> THAT INFORMATION IS PROVIDED IN THE RECOMMENDATIONS AND IN
THE YELLOW BOOK WHICH THE PEOPLE REFER TO.
THE YELLOW BOOK, WHICH ISí INTERNATIONAL HEALTH SPA
RECOMMENDATIONS FROM CDC HAS A TABLE BY COUNTRY THAT GIVES
RECOMMENDATIONS FOR BOTH THE SEASON AND THE AREAS THAT IS
REFERRED TO FROM THE RECOMMENDATIONS THAT ARE
PUBLISHED. >> DR. TURNER.
>> JIM TURNER, AMERICAN COLLEGE SHELF.
I ACTUALLY WANTED TO+ REPRESENTATIVE.
THE -- ONE OF YOUR SLIDES INDICATED THAT PRIVATE INSURANCE
PLANS GENERALLY DON'T PAY FOR THESE TRAVEL AX EVENS, BUT AS I
UNDERSTAND IT UNDER THE AFFORDABLE CARE ACT, PREVENTIVE
SERVICES INCLUDING VACCINATIONS ARE NOW SUPPOSED TO BE INCLUDED.
AND I'M NOT AWARE THAT TRAVEL VACCINES ARE EXCLUDED FROM THAT
AND I'M1óápQ"ERING ALSO THE MEDICAID POPULATION, AS WELL.
SO CAN YOU CLARIFY THAT? >> I'M ACTUALLY NOT ABLE TO
CLARIFY THAT SPECIFICALLY TODAY. ACTUALLY, AS FAR AS COVERAGE,
WHERE THIS IS INVOLVING TRAVEL BY THE INSURED, BY THE EMPLOYER,
IT IS GENERALLY COVERED. I'M GOING TO HAVE TO CLARIFY
STARTING THE AFFORDABLE CARE ACT THAT THIS IS ALSO COVERED UNDER
THAT RURAL. >> THE REASON I BRING IT UP IS
IT CLEARLY HAS COST IMPLICATIONS FOR THIRD-PARTY PAYORS AND
GOVERNMENT AGENCIES IF, IN FACT, THEY HAVE TO COVER IT.
AND WE'RE PREVENTING ONE OR TWO CASE A YEAR, IT LOOKS LIKE, FROM
YOUR DATA. >> ANN AND KRISTIN MAY WANT TO
XHEVENT ON THE AFFORDABLE CARE ACT, BUT I THINK THE VACCINESC'N
THERE ARE VACCINES IN THE RECOMMENDED TABLE AND THIS WILL
NOT BE IN THERE.>D' >> JAMIE LEHRER FROM THE AEFP.
I WOULD SUGGEST THAT FOR THE SLIDE THAT'S UP IN FRONT OF US
RIGHT NOW, THERE'S TWO SENTENCES AND THE FIRST SENTENCE, I WOULD
AGREE WITH JEFF THAT WE COULD CHANGE TO JE VACCINE IS
RECOMMENDED FOR SHORT-TERM, ETCETERA, ALL THE WAY DOWN TO
THAT PERIOD .MAKE THAT A CATEGORY A AND ONLY LEAVE THE
SECOND SENTENCE AS A CATEGORY B. >> DR. G
GROGG FROM THE AMERICAN OSTEOPATHIC ASSOCIATION.
BUT I'M SPEAK, A PERSON WHO HAS A TRAVEL MEDICINE CERTIFICATE
ñ CLINIC.
TYPICALLY, JE IS NOT REIMBURSED BY INSURANCES.
IT'S NOT INEXPENSIVE. IT'S RATHER EXPENSIVE.
IF THEY'RE SENDING SOMEBODY TO
THOSE AREAS FOR WORK RELATED ISSUES, BUT INSURANCE TYPICALLY
DOES NOT PAY FOR IT. >> DR. SMITH.
>> GENE SMITH, ACIP MEDICAL OFFICER.
THIS IS RELATING TO THE IMPLEMENTATION AND INSURANCE
QUESTIONS. WHEN WE WERE FIRST TALKING WITH
DR. FISHER ABOUT THIS, WE DID LEARN THAT AS FAR AS THE
AFFORDABLE CARE ACT THAT IS -- THAT COVERS ROUTINELYCOMMENDED
VACCINATIONS, NOT TRAVEL VACCINATIONS.
AND SECONDLY, I JUST HAD SOME PERSONAL EXPERIENCE WITH THIS
BECAUSE I JUST PUT MY 15-YEAR-OLD DAUGHTER ON A PLANE
TO NEPAL, WHERE SHE IS NOW. SO I INVESTIGATED THIS IN DEPTH,
INCLUDING TALKING WITH DR. FISHER.
AND INDEED, DISCOVERED THE SERIES COSTS ABOUT $500.
PRIVATE INSURANCE DOESN'T PAY FOR IT.
MY DAUGHTER BELONGS TO A LARGE PEDIATRIC PRACTICE IN ATLANTA
WHO DOESN'T EVEN OFFER THE VACCINE.
I GOT IN TOUCH WITH A TRAVEL CLINIC TO FOLLOW UP.
BUT MAYBE SOME OF THE PEOPLE LIKE DR. GROGG AND DR.
GERSCHMANN KNOW IT ISN'T LIKELY THAT A GENERAL PRACTICING
PEDIATRICIAN WILL BE CALLED UPON TO GIVE THIS VACCINE AND,
THEREFORE, INTERPRET THE RECOMMENDATION OR IS THE CHILD
MORE LIKELY TO GET GOING TO A SPECIALIZED TRAVEL MEDICINE
CLINIC WHO REALLY KNOWS HOW TO INTERPRET?
>> DR. GROGG AND THEN -- >> YEAH.
TYPICALLY, THEY WOULD GO TO A TRAVEL MEDICINE CLINIC.
THEY NEED --UUñ JAPANESE HE C%áVLITIS, THEY'RE PROBABLY
GOING TO NEED OTHER THINGS SUCH AS YELLOW FEVER.
>> AND DR. ZURG. >> YEAH.
I DON'T SEE HOW THE RECOMMENDATION DR. LEHRER MADE
CONFUSES THINGS, SO I WOULD LIKE TO MAKE A MOTION THAT WE ACCEPT
THE RECOMMENDATION AS PRESENTED WITH THE CHANGE THAT DR. LEHRER
RECOMMENDED THAT THIS FIRST SENTENCE BECOME CATEGORY A AND
THE SECOND SENTENCE REMAIN CATEGORY B.
>> AND I THINK I WOULD ADD TO THAT, JUST TO BE CONSISTENT WITH
DISCUSSIONS, THE SECOND SENTENCE PROBABLY SHOULD READ JE VACCINE
MAY BE USED. AS I THINK WE TRY TO GET AWAY
FROM SHOULD BE CONSIDERED AS A PHRASE AND INSTEAD UNDER
CATEGORY B+N IT'SáX MAY BE USED. >> OKAY.
CAN WE CLARIFY A POINT ABOUT IT IF WE'RE GOING TO VOTE ON THIS?
>> YEAH. >> BECAUSE THESE ARE THE
RECOMMENDATIONS FOR ADULTS CURRENTLY AND WE WERE VOTING ON
RECOMMENDATIONS FOR CHILDREN. SO THE QUESTION BE IF WE MADE
ANY CHANGES TO THESE RECOMMENDATIONS, THE ACIP,
SAYING THAT WE'RE CHANGIN'÷÷ TH RECOMMENDATIONS FOR ADULTS, --?
DIDN'T COMPLETE7D THE REVIEW FO THAT PURPOSE.
SO THE COMMITTEE NEEDS TO KNOW THAT WOULD APPLY, THEN, TO
ADULTS AS WELL AS CHILDREN, WHICH WOULD BE A CHANGE FROM
>> DR. HARRISON. >> WHY SHOULD WE NOT CHANGE THE
FIRST BE CONSIDERED TO IS RECOMMENDED?
IN B CATEGORY A? >> IAGUELY RECALL THIS BEING
DISCUSSED WHEN WE WERE FOCUSING ON THE ADULTS.
SOME OF THIS IS OCCURRING IN PEOPLE WHO HAVE SHORT-TERM
EXPOSURE. I WONDER IF SOMEBODY COULD
REMIND US ABOUT THE DENOMINATOR AND WHAT PROPORTION OF TRAVELERS
ARE SHORT-TERM VERSUS LONG-TERM. BECAUSE I BELIEVE PART OF THIS
WAS ABOUT FOCUSING IN ON A SMALL POPULATION THAT YOU COULD TRY TO
GET ADHERENCE TO AND HAVE THE PERMISSIVE RECOMMENDATIONS WHERE
YOU HAVE TO DO ADDITIONAL FACT-FINDING RELATED TO THE
LARGER GROUP. SO MAYBE YOU HAVE THE DATA?
>> YEAH. I DON'T HAVE THEM UP HERE.
I PRESENTED THEM IN FEBRUARY. THERE REALLY AREN'T VERY GOOD
DATA TO ALLOW US TO DISTINGUISH THAT.
MOST OF THE DATA ON TRAVELERS ARE BASED ON ENTRIES TO ASIAN
COUNTRIES. WE DID DO A SURVEY AT AIRPORTS
WHERE WE ASKED PEOPLE ABOUT THEIR ITINERARIES, THEIR PLANNED
DURATION OF TRAVEL AND WHAT THEY WERE GOING TO DO THERE.
BASED ON THAT, ABOUT A QUARTER OF THE TRAVELERS THAT WE
SURVEYED AT THREE AIRPORTS IN THE UNITED STATES HAD EITHER
INTENTION OF LONG-TERM TRAVEL OR SPENDING THE MAJORITY OF THEIR
TIME IN RURAL AREAS. SO IT WAS A RELATIVELY SMALL
SURVEY. I DON'T REMEMBER THE NUMBERS,
BUT HUNDREDS OF PEOPLE. THERE ARE MILLIONS OF U.S.
TRAVELERS WHO ENTER ASIAN t÷( COUNTRIES.
SO AS YOU SAY, THAT WAS OUR ATTEMPT TO FOCUS IN ON THE
PEOPLE THAT WE BELIEVE WERE AT THE TRULY INCREASED RISK OF
DISEASE. BUT THOSE ARE THE ONLY DATA I'M
AWARE OF THAT ALLOW US TO TRY TO GET AN IDEA OF THAT DENOM5T ITE
WHO WOULD NEED THAT HIGHER RISK CATEGORY.
>> I THINK THE COMMgwELñ ARE VEY GERMANE HERE BECAUSE OF THE FACT
CLINICAL PRACTICES DON'T KEEP THIS VACCINE
AVAILABLE AND IT REALLYs GOES INTO THAT REALM OF THE TRAVEL
MEDICINE. THE OTHER POINT IS, THIS -- I
THINK THE WORK GROUP TRIED TO HARMONIZE US WITH THE
PRE-EXISTING%s ADULT RECOMMENDATION.
DR. BOUCHINNI. >> I WANT TO REITERATE THAT
POINT, WE WANT TO BE CAREFUL NOT TO CHANGE THE ADULT RELATIONS
WHILE WE WERE MAKING THE RECOMMENDATIONS FOR CHILDREN AND
FELT THAT THE LANGUAGE OF THIS CURRENT RECOMMENDATION ON THE
SCREEN REALLY IS MORE OF A CATEGORY B TYPE RECOMMENDATION
BASED ON THE LANGUAGE THAT WE NOW USE TO MAKE OUR
RECOMMENDATION. SO THAT'S WHY, IN FACT, THERE
WAS ONE POINT WHERE WE ACTUALLY SPLIT,Ib THESE TWO SENTENCES AN
HAD SEPZKUz RECOMMENDATIONS AND PUT THEM BACK TOGETHER BECAUSE
THAT'S REALLY WHAT IS IN THE ADULT RECOMMENDATION.
SO JUST AS ( TRY AND DEAL
CAME BACK TO THIS APPROACH. >> DR. DUCHIN.
CO ISSUE, WOULD IT NOT BE AN
IMPROVEMENT, THOUGH, TO TAKE THAT GROUP FOR WHICH A GROUP OF
TRAVELERS THAT ARE GOING TO BE2 SHORT-TERM,uúBUT AT HIGH RISK FR
WHICH MY IMPRESSION IS WE WOULD RECOMMEND THE VACCINE, NOT JUST
CONSIDER IT AND MAYBE GIVE IT, MAYBE NOT.
WE WANT THEM TO GET IT AND PUT THEM IN THE CATEGORY OF THE
OTHER PEOPLE WOULD WANT TO GET IT.
>> WE WANTED PEOPLE TO CONSIDER THE CIRCUMSTANCES AND MAKE THE
DECISION. SO THEN MAYBE -- MAYBE OVER
TIME, THAT LANGUAGE NEEDS TO CHANGE TO REFLECT THAT.
>> YEAH. >> CONSIDER THE CIRCUMSTANCES
AND MAKE THAT DECISION. >> I THINK IF YOU LOOK AT WHAT
THAT LANGUAGE INCLUDES, IT INCLUDES A WIDE RANGE OF
DIFFERENT TRAVELERS WHO HAVE VERY SHORT-TERM TRAVEL AND ARE
GOING ONE DAY TO A RURAL AREA VERSUS PEOPLE THAT ARE TRAVELING
FOR TWO WEEKS. AND THAT'S HOW WE FELT THERE WAS
VARIATION. REGARDING THE WORDING SHOULD BE
CONSIDERED, WHICH WAS PRIOR TO GRADE RECOMMENDATIONES AND PRIOR
TO LANGUAGE WHETHER THAT WORDING SHOULD BE USED OR NOT.
BUT THAT WAS THE RATIONALE, AT LEAST AT THE TIME WHEN THESE
WERE PREPARED. >> DR. BENNET.
>> I WONDER IF THIS COULD PARTLY BE ADDRESSED BY CREATING AN
ALGORITHM THAT GET BE EASY TO FOLLOW FOR ANYONE WHO IS TRYING
TO DECIDE WHETHER TO GIVE THIS VACCINE OR NOT AND IN THE
ALGORITHM BE A BIT MORE SPECIFIC ABOUT WHAT THE CRITERIA ARE FOR
CHOOSE TO GO GIVE THE VACCINE. >> OTHER COMMENTS, QUESTIONS?
ANYONE WILLING TO MAKE A MOTION? OKAY.
OKAY. THEN WE NEED A SECOND.
DR. DUCHIN. AND IS JUST POINT OF ORDER, IS
THE MOTION FOR THE RECOMMENDATION AS IT IS LAID OUT
HERE? WELL, I NEED GUIDANCE ON THAT.
I MADE THE MOTION THINKING ABOUT THE CHILDHOOD RECOMMENDAX7
D THE IDN'T CONSIDER ADULT3HT(ááátNDATION SHOULD THEN
BE DIFFERENT. SO I'M NOT QUITE SURE HOW TO
HANDLE THAT. MY PERSONAL PREFERENCE IS THAT
WE CHANGE IT FOR BOTH, BUT I DON'T KNOW IF WE SHOULD OR CAN
DO THAT IN THIS SESSION.6 >> DR.ñ COYNE-BEASLEY.
>> I'M CHAIRMAN OF THE ADULT CHAIRMAN GROUP AND I THINK IT
WOULD BE INAPPROPRIATE TO CHANG THE ADULT RECOMMENDATION WITHOUT
CONSULTING THAT GROUP. >>Bç>t WILLINGNESS TO MODIFY TH
MOTION? >> YEAH.
I THINK IN THAT LIGHT, I THINK I WOULD MODIFY THE MOTION TO JUST
ACCEPT THE LANGUAGE AS PRESENTED HERE FOR CHILDREN AND THAT THIS
DISCUSSION MOVE FORWARD IN THE JE WORK GROUP AND THE ADULT WORK
GROUP FOR POSSIBLY CHANGING BOTH.
>> AND IS THAT ACCEPTABLE TO YOU, DR.o/Or DUhÑ÷o?
OKAY.ANYONE ELSE SECOND? SECOND.
OTHER DISCUSSION? >> LET ME MENTION THAT THE NEXT
PASS, I THINK, FOR THE WORK GROUP IS TO UPDATE THE
GUIDELINES, TO REDO THE STATEMENT FOR JE VACCINATION.
I THINK THE COMMENTS THAT WERE MADE WILL HELP US IN
REFORMATTING THIS RECOMMENDATION SO THAT IT READS MORE TOWARDS
WHAT YOU SUGGEST. AND SO I THINK THAT THAT -- AND
I THINK THE ALGORITHM WOULD HELP, AS WELL.
AND I THINK WE CAN LOOK FOR THOSE TO HELP CLARIFY THIS IN
THE FUTURE WHEN THE NEW RECOMMENDATIONS COME THROUGH THE
COMMITTEE. >> THANK YOU.
DR. LEHRER. >> TWO COMMENTS.Nx?a
DID YOU WANT TO CHANGE THIS SHOULD BE CONSIDERED WORDING?
AND THE SECOND COMMENT IS THE WAY THIS IS PHRASED HAS NO
COMMENTS REGARDING ADULTS OR PEDIATRICS.
SO I'M NOT SURE IF THERE'S A HEADER SOMEWHERE THAT SAYS THIS
IS ONLY FOR PEDIATRIC RECOMMENDATION, BUT THIS IS JUST
ANY VACCINE TRAVELER AND TRAVELER TO THE AREA.
>> WELL, WE'RE JUST EXTENDING THE AGE GROUP FOR THE
RECOMMENDATION SO THAT THERE DEFINE THAT THE AGEcR GROUP HAS
BEEN EXTENDED, BUT THE RECOMMENDATIONS WILL STAY THE
SAME. >> CORRECT.
YEAH. TO PUT IT IN -- AGAIN, WHEN
THESE WERE PASSED, THERE WERE TWO VACCINES THAT WERE LICENSED
FOR USE IN DIFFERENT AGE GROUPS. SO BASICALLY IN THE CURRENT
RECOMMENDATIONS THAT'S COVERED UNDER EACH VACCINE STATING ITS
LICENSE AND RECOMMENDED FOR USE IN THIS AGE GROUP VERSUS THAT.
SO CURRENTLY THESE RECOMMENDATIONS APPLY TO THE TWO
DIFFERENT AGE GROUPS. WE WILL EXTEND THAT AND IN A
POLICY NOTE WILL NOTE THE LICENSURE.
I MIGHT SAY THE REPORTS AND RECOMMENDATIONS DO HAVE A BOX.
I'M NOT SURE IT'S QUITE AN ALGORITHM.
BUT THERE IS A BOX THAT DELINEATE TESS RECOMMENDATIONS
AND THE CONSIDERATION CATEGORY THAT PROVIDE THAT TYPE OF
DETAIL. >> AND DR. DUCHIN.
>> JUST CLARIFY. I'M A LITTLE CONFUSED.
IF THIS LANGUAGE APPLIES TO BOTH ADULT AND PEDIATRIC, WHAT IS THE
BARRIER TO CHANGING THE RECOMMENDATION TO INDICATE THAT
PEOPLE WHO ARE SHORT-TERMúóa TRAVELER AND HIGH RISKalURT
VACCINATED, IF THAT WOULD COVER BOTH POPULATIONS ANYWAY?
>> YEAH. THERE'S NOT A BARRIER, BUT WE
CAME -- THE VOTE WAS FOR EXTENDED THE USE OF THE VACCINE
IN CHILDREN. THAT'S WHAT WAS PRESENTED.
I JUST WANTED THE PEOPLE TO BE AWARE THAT IF YOU DID VOTE ON
THAT, THAT THAT WOULD BE CHANGING THE RECOMMENDATIONS FOR
ADULTS OR WE WOULD HAVE DIFFERENT RECOMMENDATIONS FOR
THE TWO AGE GROUPS. >> I SEE.
BUT THERE'S NO REASON NOT TO MAKE THAT SAME CHANGE FOR
ADULTS, IS THERE? >> I THINK THAT'S UP TO THE ACIP
TO DECIDE THAT. BUT THESE ARE THE EXISTING
RECOMMENDATIONS THAT THIS COMMITTEE VOTED ON, 2009, FOR
USE IN ADULTS. SO YOU WOULD BE -- UNLESS YOU
WANTED TO HAVE DIFFERENT RECOMMENDATIONS FOR THE TWO AGE
GROUPS IF YOU VOTED ON THAT THAT WE WOULD APPLY IT TO ADULTS AND
THAT WOULD NEED TO BE PUBLISHED IN THAT WAY.
PO RECOMMENDATIONS ARE EXTENDED TO
THE USE IN CHILDREN. >> AND I BELIEVE THE COMMENTS OF
DR. COYNE-BEASLEY AND DR. BOUCCHINNI ARE APPROPRIATE HERE
IN TERMS OF TAKING THIS BACK TO THE WORK GROUP, CONSIDERING
MAKING -- I'M USING THE WORD, TOO, MAKING THAT CHANGE TO MAYBE
"MAY BE USED" FOR EXAMPLE AND ALSO MOVING THAT FIRST SENTENCE
INTO THE RECOMMENDED AND RETURNING THIS TO THE IP PERHAPS
AT THE NEXT MEETING.y DR. KEITELOlS4u AND DR. --
>> I GUESS I'M= CONFUSED, TOO.d TO A CERTAIN EXTENT, IT DEPENDS
ON WHETHER WE ALL AGREE THAT SHORT-TERM TRAVELERS WHO HIGH
RISK AREAS DURINGé:ñ THE SEASON TRANSMISSION WOULD MAKE US SAY
YOU SHOULD RECEIVE THE VACCINE. TO A CERTAIN EXTENT, THAT'S --
WHAT WE'RE SAYING, I APPRECIATE DR. BOCCHINNI SAYING THAT WE
LACK THE DENOMINATOR DATA. I'M NOT SURE THAT IS HOW THE
PEOPLE AROUND THE5misU((SQ FEEL. IF YOU'RE REALLY GOING TO A HIGH
ON RISK AREA, WHERE THERE'S TRANSMISSION OCCURRING, WOULD
YOU IN YOUR ALGORITHM SAY THAT PERSON SHOULD GET THE VACCINE?
>> DR. CAMPOS-OUTCALT. >> TO ME, HIGH RISK IS A
RELATIVE TERM. I'M NOT SURE I WOULD SAY HIGH
RISK, I WOULD USE HIGHER RISK. BECAUSE IT APPEARS THAT HIGH
RISK -- THAT IT'S PRETTY LOW RISK, REGARDLESS.
SO TO ME, THIS IS A B RECOMMENDATION WHERE YOU REALLY
WANT TO CONSIDER YOUR CIRCUMSTANCES, WHAT KIND OF RISK
MIGHT YOU BE AT? GET THE BEST AVAILABLE DATA,
LOOK AT HOW ELSE YOU CAN PROTECT YOURSELF AND MAKE A DECISION
Ñ MEETS THAT DEFINITION GETS THE
VACCINE. I THINK IT IS A B.
>> I LIKE THE IDEA OF EXTENDING THE AGE RANGE TODAY, HAVE A VOTE
AND READDRESSING THIS AT THE NEXT MEETING.
I DON'T THINK WE CAN RESOLVE IT NOW.
>> OTHER COMMENT? WE HAVE A MOTION AND SECOND.
AS IT STANDS. AND I BELIEVE WE CAN START OUT
WITH A VOTE AND WE'LL -- OH, DR. BENNET.
>> CAN YOU JUST CLARIFY ONE THING?
THERE WAS DISCUSSION OF CHANGING WORDING AND I JUST WANT TO BE
CLEAR, ARE WE VOTING ON THE WORDING AS IT CURRENTLY EXISTS
OR WITH CHANGE? >> WE'RE VOTING ON THE WORDING
AS IT IS PRESENTED IN THIS SLIDE AND IN THE OTHER TWO SLIDES, AS
WELL. I THINK THE QUESTION IS CHANGING
IT MAY BE USED AND I THINK AT THIS POINT IN TIME FOR
HARMONZATION BETWEEN THE EXITING JE ADULT RECOMMENDATION AND THIS
ONE, WE KEEP"S AND HAVE THAT BROUGHT BACK AT A
FUTURE MEETING. >> I APPRECIATE ALL THE
DISCUSSION, BUT I DON'T KNOW WHY WE WOULDN'T CHANGE THIS TO MAYBE
USE NOW SINCE THAT'S THE KIND OF LANGUAGE WE'RE HOPING TO USE FOR
THE FUTURE. >> AND THE QUESTION IS WHETHER
OR NOT WE COULD LIVE FOR FOUR MONTHS WITH -- O SHOULD BE
CONSIDERED OR NOT AND BRINGING THAT BACK.
TO BE HONEST, I THINK LIVE EITHER WAY.
>> BUT I DO THINK THE IMPORTANCE OF HARMONZATION IS SIGNIFICANT.
IN A VACCINE YOU'RE NOT GOING TO GIVE VERY OFTEN ANYWAY AND WHO
WANTS TO MAKE PEOPLE CRAZY? >> THE NICE THING IS, WE'RE
QUIBBLING OVER MINOR POINTS AS OPPOSED TO THE BIGGER PICTURE
AND I THINK THAT IS TESTIMONY AS TO HOW NICELY THE EVIDENCE WAS
PRESENTED TO ACIP. AGAIN, THANKS, DR. FISHER.
ARE THERE OTHER COMMENTS? HEARING NONE, MAY I PICK ON DR.
SAWYER AND LET'S GO COUNTER CLOCKWISE.
>> SAWYER, YES. >> VASQUES, YES.
>> COYNE-BEASLEY, >> REUBEN, YES.
DUCHIN, YES. >> HARRIMAN, YES.
>> KEITEL, YES. >> TEMTE, YES.
>> BENNET, YES. >> CAPOS-OUTCALT, YES.
>> AND THE MOTION IS APPROVED UNANIMOUSLY.
AND I BELIEVE WE HAVE EARNED A BREAK TIME.