Vaccine Safety Evaluation: Post-marketing Surveillance Conference

1. 1 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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3. 3 Meningococcal disease isolate serogroup and dominant subtype 1990 -2005{not including PCR positive cases}

4. 4 The problem Major epidemic Strain specific outer membrane vesicle (OMV) vaccine - MeNZB� Clinical trials in Auckland

5. 5 The Problem (cont) Licensure application - ~1100 recipients ~3300 doses* Substantial experience with other OMV vaccines � Norway, Cuba and Walter Reed outer membrane protein vaccine

6. 6 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

7. 7 The Solution � Safety Monitoring System National Immunisation Register (NIR) - with same patient identifier used in hospitals Several data sources

8. 8 Several data sources CARM Passive reporting system Intensive Vaccine Monitoring Programme (IVMP) Hospital based monitoring All event Rare event

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10. 10 Several data sources CARM Passive reporting system Intensive Vaccine Monitoring Programme (IVMP) Hospital based monitoring All event Rare event

11. 11 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

12. 12 Hospital Based MonitoringRare Event Events of interest A priori determined case definitions Independent case ascertainment � Clinical Review Committee (CRC)

13. 13 Hospital Based MonitoringRare Event (cont) Background disease rates Thresholds � stop/go points Minimum data sets

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15. 15 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.

16. 16 Independent Safety Monitoring Board Separation of data collection and analysis from assessment Independent assessment - Independent safety Monitoring Board (ISMB)

17. 17 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

18. 18 Conclusion AS of June 2006 > 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�

19. 19 Acknowledgements Meningococcal Management Team (MMT) and Advisors Professor Diana Lennon, Dr Jane O�Hallahan, 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 All vaccinators and others involved in the programme.

20. 20 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-vaccinestrategy.pdf Safety Monitoring Plan � NZ Ministry of Health http://www.moh.govt.nz/moh.nsf/pagesmh/5220/$File/safety-monitoring-plan.pdf

21. 21 Back up slides

22. 22 Observed vs expected cases Total population e.g. Acute flaccid paralysis

23. 23 Observed vs expected cases Vaccinees only e.g. seizures

24. 24 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.

25. 25 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

26. 26 Target population Reside in Counties Manukau, Auckland, Waitemata and Northland DHB�s. Target Cohorts 100,000 aged 5 � 19 years in CMDHB and Auckland DHB�s 100,000 aged 0 - 4 years in all 4 DHB�s

27. 27 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. 

28. 28 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.

29. 29 Intensive Vaccine Monitoring Programme Prospective observational cohort study of MeNZB� vaccine

30. 30 IVMP sentinel practice monitoring Monitoring cohort Infants < 19 months who have an immunisation in the practice All Immunisations

31. 31 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

32. 32 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 !!

33. 33 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 AEFI�s)

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35. 35 Key Findings Low opt-out rate (10/17921) No unexpected AEFI�s identified Low rate of reactogenicity Reaction profile similar to Routine immunisations

36. 36 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