Is MeNZB Safe

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Is MeNZB Safe?

• Stewart Reid
• On behalf of the MMT
• The Really Active Immunisation Conference,
• Rotorua, 11/9/04

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MeNZB Related-Vaccine Safety Data

• Substantial safety data exist
• 350,000 doses Norwegian Parent Vaccine
  administered to 175,000 recipients (including gt
  80,000 recipients in a RCT)
• 65M doses of similar Cuban vaccine
• 40,000 doses of the Walter Reed Institute
  Vaccine
• 1,000 doses of the RIVM (includes infants and
  toddlers

3
MeNZB Safety Data Base

• Currently stands at around 4000 doses
• Data has been presented by Philipp Oster
• This presentation concerns the post licensure
  safety surveillance

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MeNZB? Post Licensure Safety Surveillance

• Stewart Reid, Anne McNicholas
• Yvonne Galloway, Paul Stehr-Green
• Claire Macdonald, Sarah Radke,
• Michelle van der Raaij

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Why is post licensure safety surveillance needed?

• Post licensure safety surveillance is routine
• First widespread use of this vaccine
• Events will occur following receipt of MeNZB

6
Immunisation Safety Surveillance - Objectives

• Comprehensive vaccine safety monitoring
• identify events caused by vaccination
• Enable causality assessment for events which
  follow vaccination,
• Increase public confidence in vaccine programs
• avoid reductions in coverage caused by
  unsubstantiated fears of vaccine reactions.

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Safety Surveillance methods

• CARM
• Passive Intensive - IVMP
• Hospital based Monitoring
• Rare event All event
• Background disease rates
• Data Base matching
• Independent Safety Monitoring Board

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CARM Passive 1

• Standard passive monitoring system
• High rate of reporting in NZ
• Under reporting the norm
• Events with close temporal relationship more
  likely to be reported
• Information may be incomplete for adequate
  assessment

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CARM Passive 2

• Causality assessment can be difficult
• Local reactions, isolates (mumps/ polio) are
  exceptions
• Denominator may be poorly defined
• May be spurious reasons for increased reports

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CARM Passive 3

• Reporting stimulated by
• Encouraging primary care providers to report
• letter from CARM with ae report cards -
• Providing information on events reported
• Designed to increase passive CARM reporting in
  early stages of vaccination campaign

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Intensive Vaccine Monitoring Programme - IVMP

• Based on Lakshmann et al Arch Dis Child
  200185391-97 piloted in Otago
• For vaccinations given to those aged less than 19
  months
• Sample of GPs send full clinical records 6 weeks
  after immunisation
• This can be done seamlessly and electronically

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IVMP

• To provide event reporting following routine
  schedule
• To develop data base which over a several years
  may become large enough to provide frequency
  estimates on rarer events
• It may be possible to use the GP database to
  investigate events with longer latency

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IVMP in CMDHB

• In South Auckland this system will operate for
  those aged lt 5 rather than lt 19 months.
• To provide surveillance for adverse events not
  involving hospitalisation in this age group
  during early vaccine use.

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Safety Surveillance Methods

• CARM
• Passive Intensive - IVMP
• Hospital based Monitoring
• Rare event All event
• Background disease rates
• Data Base matching
• Independent Safety Monitoring Board

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Hospital Monitoring

• Based on Canadian IMPACT system
• Can J Infect Dis 19934194-5
• Real time during pilot roll-out
• Two components
• 1. Rare event
• 2. All events

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Hospital Monitoring - Rare Events 1

• Hospital admission data-base screened daily for
  specified events
• e.g. neurological events, HHE, Anaphylaxis, ITP
• Immunisation status and temporal relationship
  established using NIR and NHI No.
• Case definitions established
• Case report forms designed

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Hospital Monitoring - Rare Events 2

• Clinical review committee
• determine that cases fulfill case definition
  assist in full investigation of cases
• To detect clusters requiring further assessment
  or
• which may be sufficiently severe to stop vaccine
  use

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Rare events to be monitored

• Anaphyllaxis
• Encephalopathy/encephalitis
• Flaccid paralysis
• Thrombocytopenia
• HHE
• Seizures
• Petechial rashes
• catch all categories e.g. all intensive care
  admissions within 7 days/ unusual events thought
  to be related to immunisation/Deaths - SIDS

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Hospital Monitoring - All Events

• Hospital admission data base compared to NIR data
  base to establish admissions occurring within 7
  days of immunisation
• Retrospective analysis of discharge diagnosis
• Descriptive analysis only but may provide data
  for preliminary assessment of alleged AEFI
• May indicate AEFI requiring further investigation

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Target population

• Reside in Counties Manukau, Auckland, Waitemata
  and Northland DHBs.
• Target Cohorts
• 100,000 aged 5 19 years in CMDHB and Auckland
  DHBs
• 100,000 aged 0 - 4 years in all 4 DHBs

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Hospital based monitoring

• For the period 1/4/04 18/7/04
• 10,371 ED attendances and admissions screened
• 648 cases of interest detected
• 603 met screening criteria
• Audit 586 notes screened
• 2 additional cases found both petechial
  rashes

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Safety Surveillance methods

• CARM
• Passive Intensive - IVMP
• Hospital based Monitoring
• Rare event All event
• Background disease rates
• Data Base matching
• Independent Safety Monitoring Board

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Background Disease Rates

• For hospital monitored events the incidence over
  the last 5 10 years will be defined using
  hospital discharge data
• Data on each disease categorised by age, sex,
  ethnicity, season and DHB etc.
• To provide background data against which events
  following vaccination can be compared.

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Data Base Matching 1

• Methodology which can be used for causality
  assessment for rare events
• Based on Farrington et al Am J Epidem
  19961431165-1173
• Depends on being able to match NIR with hospital
  discharge data base
• Require event to be investigated which may be
  caused by immunisation and a time period within
  which vaccine could cause the event

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Data Base Matching 2

• Case series analysis has been shown to be as good
  as cohort or case control methodology to
  establish causality
• Establish frequency of target event in time
  periods around vaccination
• If events clustered in putative time period
  following vaccination compared to other time
  periods before and after vaccination then that
  suggests causality

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Independent Safety Monitoring Board

• review all safety data
• Independent with Australian chair and four other
  members, one from USA
• Advise on cessation of vaccination because of
  safety risk
• Advise on further investigation of possible
  safety risks

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Is MeNZB safe?

• The available data suggest MeNZB is safe
• Monitoring will detect any concerns in a timely
  manner
• Adverse events following administration of MeNZB
  will occur and cause concern
• Independent scientific assessment of possible
  adverse events will be carried out by the ISMB

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The End