Pharmacovigilance and Risk Management Questions for the Committee

1
Pharmacovigilanceand Risk Management
Questions for the Committee
2
Pharmacovigilance PlanSafety Specification

• Safety Signals Identified
• Wheezing within 42 days post-vaccination
• Respiratory-related hospitalizations
• Overall hospitalizations

3
Safety SpecificationLimitations of Available
Data

• Study MI-CP111 excludes children with
• (A) Medically-diagnosed or treated wheezing
  within 42 days before enrollment
• (B) History of severe asthma

4
Pharmacovigilance Plan

• Proposed actions
• Passive surveillance
• Spontaneous and accelerated (monthly) reporting
• Observational cohort study in HMO setting
• 20,000 vaccinees aged lt5 years
• 90 power to observe statistically significant
  increase in relative risk if true RR gt2.5 for
  events occurring at a rate of 1 in 1000
• Will also estimate rate of vaccination errors

5
Risk Minimization Tools

• Applicant proposes
• (1) Age restriction on label indication
• Screening for History of Asthma or Wheeze
  using Vaccine Information Sheet (VIS)

6
Effect of History of Wheeze

• In MI-CP111, removing subjects with a history of
  wheezing from analyses results in
• Signal for all cause hospitalization in 6-23
  month old strata weakens
• Signals for MSW and MSW-related hospitalizations
  remain in children lt24 months
• Regardless of history of wheezing, no significant
  safety signal for children gt24 months
• Passive surveillance (VAERS) data suggest some
  people with wheezing get FluMist despite label
  WARNINGS

7
Risk Management Issues

• Age as a risk management tool
• Users familiar with age restrictions for FluMist
• VAERS data suggestive of successful use of age
  restriction
• Screening on history of asthma/wheeze
• No prospective data on effectiveness of VIS as
  screening risk management tool
• Asthma/wheezing highly prevalent in young
  children
• Difficulty in defining history of wheeze and
  history of asthma in youngest ages
• Additional complication of use in routine practice

8
Questions for the Committee

• 1. Do the data demonstrate the efficacy of
  FluMist for prevention of influenza illness in
  the following
• the applicant's proposed population, i.e.,
  children age 12-59 months without history of
  wheeze?
• children in the age strata 6 23 months?
• children in the age strata 24 59 months?

9
Questions for the Committee(continued)

• 2. Do the safety data demonstrate that the
  benefits will exceed the risks of FluMist for use
  in
• a. the applicants proposed population, i.e.,
  children age 12-59 months without history of
  wheeze?
• children in the age strata 6 23 months,
  regardless of wheezing history?
• c. children in age strata 24- 59 months,
  regardless of wheezing history?

10
Questions for the Committee(continued)

• 3. If approved for children less than 5 years of
  age, what additional post-marketing studies or
  surveillance activities would you recommend?