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Proposed Pharmacovigilance Plan for H5N1 Influenza Virus Vaccine

Patrick Caubel, MD, PhDHead of Pharmacovigilance North America

February 27, 2007

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Background

Planning for the prospect of pandemic influenza is one

of the most effective steps to mitigate the impacts of

such an event

Vaccination remains a critical defense against pandemic

influenza

Vaccine safety monitoring is necessary Part of a comprehensive public health surveillance program

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Pharmacovigilance Plan Objectives

Detect, evaluate and minimize risks due to the pandemic

influenza vaccine

Contributes to the benefit-risk evaluation in a pandemic

situation

Agree beforehand on: Objectives for postmarketing safety surveillance

Collaborative plan with key stakeholders

Put in place an adequate system tailored to a pandemic situation to allow adequate responses

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Pharmacovigilance (PV) Planning

PV activities have to be designed considering the

following:1. Limited clinical data available

2. High volume of safety data anticipated within a short time frame

3. Increased public anxiety with AEs (adverse events) reported, regardless of causality

4. Limited personnel in industry and regulatory agencies

5. Possible disruption of pharmacovigilance systems

Need for an on-going safety signal detection and

evaluation

Feasibility and effectiveness of the proposed actions/

measures need to be tested prior to the pandemic

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Pre-pandemic: Standard PV Practices

Applicable in pre-pandemic period: Spontaneous reporting

Aggregate reports at defined time intervals

Signal detection and analysis

Safety surveillance studies (possible cohort study in first responders)

Passive collection of vaccine failure reports

Objective: Develop a better understanding of vaccine

safety profile that could impact pandemic safety

monitoring

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Pandemic: Proposed PV Practices

Applicable in pandemic situation:Spontaneous reporting with a focus on special AEs

Simplified aggregate reports

Real time signal detection and analysis

Safety surveillance studies (in early recipients after pandemic is declared)

Passive collection of vaccine failure reports

Objective: Allocation of available resources on tasks

critical for understanding the evolving benefit-risk

profile in a pandemic situation

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Spontaneous Reporting:Data Collection

Spontaneous reporting will remain the basis for safety

evaluation

One common simplified and targeted collection form

could be used by all parties when the vaccination

process begins

Healthcare professionals and patients should be

encouraged to report primarily serious adverse events,

life-threatening events, adverse events of special

interest (AESI), and deaths

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Spontaneous Reporting:Adverse Events of Special Interest

All parties must consider a list of adverse events of

special interest (AESI) for which a common case

definition will be used in order to ensure harmonized

safety assessment

EMEA has proposed a list of AESI for pandemic vaccine

surveillance

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Spontaneous Reporting: Safety Database

Rapid and open communication and information sharing

between sanofi pasteur, other vaccine manufacturers

and Authorities/Public Health Services (FDA, CDC, state

and local authorities) is essential

Electronic communication should be established prior

to the pandemic period

One single safety database dedicated to flu pandemic

vaccines could be used and shared by all parties

(VAERS database)

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Aggregate Reports

Periodic Safety Update Reports (PSURs) are prepared at defined time intervals; however, during the pandemic period due to limited resources, preparation and submission of PSURs may not be feasible

Options:

Simplified PSURs

Focusing on serious adverse events, deaths, life-threatening events, and AESI can be prepared.

PSURs prepared on an ad-hoc basis upon request from Health Authority

An aggregated PSUR will be submitted when the pandemic is declared finished

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Signal Detection and Analysis

Crude inspection of single cases or line-listings not adequate

Quantitative and automated data-mining methods should be considered (e.g. proportional reporting ratios, Bayesian methods)

Modification of standard methods may be required (stratifications, use of appropriate comparator)

May detect increase in incidence of AESI and support detection of unexpected AEs

Should be tested with seasonal flu vaccines

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Monitoring for Vaccine Effectiveness

There is no vaccine that is 100% effective

Vaccine failure evaluation done through

pharmacovigilance monitoring should not be used to

assess vaccine effectiveness

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Safety Surveillance Studies

Safety profile will remain unknown in numerous

populations prior to vaccination campaign

Consideration should be given to initiating cohort

studies either prior to the pandemic (first responders,

critical workers) or after the pandemic is declared (early

recipients)

Case-control studies using large population-based

databases (e.g. Vaccine Safety Data Link) may be useful

for rare serious AEs

Should be coordinated by national and international

public health agencies

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Summary

Streamlining and prioritization are essential for early detection and communication of potential risks

Pharmacovigilance plan and information-sharing system could be tested and harmonized during the forthcoming and subsequent flu seasons

Proposed pharmacovigilance actions are part of an evolving plan to be refined with key stakeholders, together with roles and responsibilities

Sanofi pasteur is committed to global pandemic preparedness

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Conclusion

Safety of our vaccines are of paramount importance for

sanofi pasteur.

Sanofi pasteur is prepared to work with the Government

on efficient methods of collecting safety and

effectiveness data.