Vaccine Safety Evaluation: Postmarketing Surveillance Conference

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Vaccine Safety Evaluation Post-marketing
Surveillance Conference

• New Zealand Experience with Meningococcal Vaccine
  Post-marketing Surveillance
• Stewart Reid
• 11th April 2007

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Population 4M Maori 14 Pacific
7 Asian 9 European 70 Location
South Pacific Australia 3 hours West LA 12
hours North East
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Meningococcal disease isolate serogroup and
dominant subtype 1990 -2005not including PCR
positive cases
Epidemiology of meningococcal disease in New
Zealand 2005 ESR May 2006
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The problem

• Major epidemic
• Strain specific outer membrane vesicle (OMV)
  vaccine - MeNZB
• Clinical trials in Auckland

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The Problem (cont)

• Licensure application - 1100 recipients 3300
  doses
• Substantial experience with other OMV vaccines
  Norway, Cuba and Walter Reed outer membrane
  protein vaccine

Vaccine 23 (2005) 2191 -2196.
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The Problem (cont)

• Intention to vaccinate 1,000,000 New Zealanders
  aged 6m -19y
• No National Immunisation Register (NIR)
• Only monitoring - Centre for Adverse Reaction
  Monitoring (CARM) - passive reporting

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The Solution Safety Monitoring System

• National Immunisation Register (NIR)
• - with same patient identifier used in hospitals
• Several data sources

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Several data sources

• CARM
• Passive reporting system Intensive Vaccine
  Monitoring Programme (IVMP)
• Hospital based monitoring
• All event
• Rare event

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Several data sources

• CARM
• Passive reporting system Intensive Vaccine
  Monitoring Programme (IVMP)
• Hospital based monitoring
• All event
• Rare event

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Rare events to be monitored

• Anaphylaxis
• Encephalopathy/encephalitis
• Flaccid paralysis
• Thrombocytopenia
• Hypotonic hypo-reponsive episodes
• Seizures
• Petechial rashes
• catch all categories e.g. all intensive care
  admissions within 7 days/ unusual events thought
  to be related to immunisation/deaths

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Hospital Based MonitoringRare Event

• Events of interest
• A priori determined case definitions
• Independent case ascertainment Clinical Review
  Committee (CRC)

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Hospital Based MonitoringRare Event (cont)

• Background disease rates
• Thresholds stop/go points
• Minimum data sets

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Under 5 ThresholdMinimum dataset

• All 4 Northern District Health Boards to rest of
  country
• 16 months 4 years 30,000 1st doses
• 6-16 months 7,500 1st doses
• 6 weeks 5 months 4,000 1st doses
• At each of these points substantial data was
  available on those vaccinated in Counties Manukau
  DHB.

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Independent Safety Monitoring Board

• Separation of data collection and analysis from
  assessment
• Independent assessment - Independent safety
  Monitoring Board (ISMB)

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Safety Monitoring Plan

• Discussed with Chair ISMB during development
• Reviewed and approved by ISMB
• Included
• monitoring methods,
• case definitions,
• background disease rates,
• cluster investigation protocol and
• causality assessment discussion

http//www.moh.govt.nz/moh.nsf/pagesmh/5220/File/
safety-monitoring-plan.pdf
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Conclusion

• AS of June 2006 gt 3,000,000 doses given
• ISMB review concluded
• outstanding programme of sensitive and
  objective safety monitoring
• no evidence of any significant adverse health
  event associated with the vaccine

http//www.moh.govt.nz/moh.nsf/pagesmh/5220?Open
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Acknowledgements

• Meningococcal Management Team (MMT) and Advisors
• Professor Diana Lennon, Dr Jane OHallahan, Dr
  Philipp Oster, Professor Kim Mulholland.
• Sue Crengle, Diana Martin, Liane Penney, Teuila
  Percival, Stewart Reid, Joanna Stewart
• MVS Trial Team, Auckland University
• Laboratory staff, Institute of Environmental
  Science and Research
• Independent Safety Monitoring Board and Clinical
  Review Committee
• MVS Safety Team, Ministry of Health
• Anne McNicholas, Yvonne Galloway, Paul
  Stehr-Green et al,
• Centre for Adverse Reaction Monitoring (CARM) Dr
  Michael Tatley et al
• Safety monitoring teams at participating
  hospitals
• Rest of MVS team, Ministry of Health

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References

• Strategy -
• Sexton K, Lennon D, et al. 2 articles
• NZMJ 20 August 2004, Vol 117 No 1200
• http//www.nzma.org.nz/journal/117-1200/1026/
• http//www.immunise.moh.govt.nz/documents/nzmj-vac
  cinestrategy.pdf
• Safety Monitoring Plan NZ Ministry of Health
• http//www.moh.govt.nz/moh.nsf/pagesmh/5220/File/
  safety-monitoring-plan.pdf

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Back up slides
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Observed vs expected cases

• Total population e.g. Acute flaccid paralysis

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Observed vs expected cases

• Vaccinees only e.g. seizures

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Immunisation Safety Surveillance

• A system that comprehensively monitors vaccine
  safety
• Should identify events caused by vaccination
• Enable causality assessment for events which may
  be caused by vaccination,
• Increase public confidence in vaccine programs
  helping to avoid reductions in coverage caused by
  unsubstantiated fears of vaccine reactions.

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Independent Safety Monitoring Board

• Reviewed all safety data during the period of
  hospital based monitoring
• 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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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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Consent for MeNZB

• 08 July 2004 consent for individuals aged 6
  months or older valid for 2 years
• 03 February 2005
• consent for individuals aged 6 weeks or older.
• 12 January 2006
• consent for 4th dose of the vaccine to infants
  who received the first dose when aged less than
  6 months of age.
• 21 July 2006
• renewal of Provisional Consent under Section 23
  of the
• Medicines Act 1981, valid for 2 years from 8 July
  2006.

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Medicines Act 1981 section 23

• The Minister may, by notice in the Gazette, in
  accordance with this section, give his
  provisional consent to the sale or supply or use
  of a new medicine where s/he is of the opinion
  that it is desirable that the medicine be sold,
  supplied, or used on a restricted basis for the
  treatment of a limited number of patients.

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Intensive Vaccine Monitoring Programme

• Prospective observational cohort study of MeNZB
  vaccine

6/52
Immunisation (s)
All health care visit details
Sentinel Practices across NZ (primary health
care providers)
events
incidents
reactions
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IVMP sentinel practice monitoring

• Monitoring cohort
• Infants lt 19 months who have an immunisation in
  the practice
• All Immunisations

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IVMP sentinel practice monitoring

• Monitoring cohort
• Selection of practices
• 35 large medical centres (known as sentinel group
  practices)
• MedTech32 Practice Management Software
• Population geographically socio-demographically
  diverse

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IVMP sentinel practice monitoring

• Monitoring cohort
• Selection of practices
• Data collection
• Software extraction from existing PMS data fields
• All immunisations (MeNZB other)
• All health consultation details for the six weeks
  following an immunisation
• Secure electronic transfer from PMS
• Background mode
• no additional work required at practice !!

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IVMP sentinel practice monitoring

• Monitoring cohort
• Selection of practices
• Data collection
• Events assessment
• Events assessed as unrelated (incidents) or
  related (reactions)
• Standardised coding and entry into IVMP database
• WHO National Centres causal relationship (after
  Karch Lasagna)
• WHOART (event terminology)
• Grouped by related event terms (modified for
  clinical AEFIs)

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52,754 Vac-visits (17,921 vaccinees)
10 vaccinees opted out
19 July 2004 30 Sept 2005
22,385 Vac-visits not yet assessed
IVMP Cohort groups
30,369 Vac-visits assessed
11,112 Vac-visits excluded1
19,257 Vac-visits (10,308 vaccinees) analysed
lt 6 month olds 6, 749 vac-visits (3,156 vaccinees)
6-lt19 month olds 4,474 vac-visits (2,368
vaccinees)
19 month 5 year olds 8,034 vac-visits (4,784
vaccinees)
MeNZB Vac-visit 1,166
Hybrid Vac-visit 2,452
Routine Vac-visit 3,131
MeNZB Vac-visit 3,540
Hybrid Vac-visit 441
Routine Vac-visit 493
Routine Vac-visit 209
Hybrid Vac-visit 304
MeNZB Vac-visit 7521

• 1 Outside of defined time periods
• lt 6 month olds, 03 Feb. 2005 - 30 Sep. 2005
• 6 month olds, 19 Jul. 2004 - 15 Nov. 2004

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Key Findings

• Low opt-out rate (10/17921)
• No unexpected AEFIs identified
• Low rate of reactogenicity
• Reaction profile similar to Routine immunisations

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ConclusionIVMP is a novel valuable
Pharmacovigilance tool

• Source of representative unbiased data
• Minimal participant compliance burden
• EDT technologies result in resource savings and
  efficiencies
• Real life real time vaccine campaign monitoring
• Feedback in real time to Programme leaders
• Reassurance to public
• Database available for long term follow-up