Safety of Vaccines Some Principles

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Safety of VaccinesSome Principles

• Alastair J.J. Wood M.D.
• Managing Director
• Symphony Capital LLC

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Therapy and PreventionDifferences

• Therapyperson at risk of an AE is the person who
  derives benefit
• Preventioneveryone at risk of an AE but only a
  few benefit
• Therapywe know who benefited and who had an AE
• Preventionwe never know who benefited but we
  know who had an AE

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Prevention vs. Therapy

• Therapy there is an individual risk/benefit ratio
• Prevention there is no individual risk/benefit
  ratio
• It is a population risk/benefit
• Population risk/benefits change according to the
  populations potential for benefit
• But individual risk of an AE is constant

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Vaccine SafetyDynamics of Population
Safety/Benefit

• Knowledge of safety even more critical
• Hard to have an individual risk/benefit
  discussion
• Define population risk of disease
• E.G. SmallpoxU.S. 2007 smallpox deaths?
• Define population risk from vaccine
• Population includes potential risk to others
• Damage to public credibility of vaccines?

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Vaccine Safety Post VioxxLessons
LearnedCounterintuitive

• Types of adverse reactionsRare in background
  populationliver failure
• Reasonably easy to pick up an increase
• Even a 4X increasestill small absolute numbers
  of cases
• Common in background populationMI
• Impossible to see in spontaneous reports
• What does a Viioxx MI look like?
• 4X increasemassive public health impact
• Hundreds of thousands injured!

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Vaccine Safety Post VioxxLessons Learned

• Spontaneous reporting systems
• Limited utility
• Post marketing surveillance
• Rare (in background)potentially useful
• Common (in background)not likely useful
• Need a comparison group

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Vaccine Safety Post VioxxLessons Learned

• However for vaccines in children
• Common morbidities do not occur
• Thus the Vioxx lesson not as relevant
• Rare events (in background) are risks
• Spontaneous reporting systems potentially
  effective
• No hypothesis for increase in common events of
  major morbidity/mortality importance

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Vaccine Safety Post VioxxLessons
LearnedConflicts of Interest

• FDA does not promote drugs!
• Yet concerns about independence of approval and
  safety
• Independence of OSE
• Reporting structure
• Resources
• Can FDA second guess itself?
• CDC does promote vaccinations!
• Can CDC second guess itself?
• Will/should public be comfortable?

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Vaccine Safety Post VioxxLessons
LearnedConflicts of Interest

• CDC does promote vaccination
• If a problem occurs will public be comfortable
  with independence of judgments on
  safety/efficacy?
• Need independent safety review
• Clinical trial DSMBs may be a model
• Appearance, independence and transparency is the
  issue
• Reporting structure

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Vaccine Safety

• Pre-marketing safety evaluation
• Post marketing review
• Regular at fixed frequencies?
• Incidents?
• Public review?
• Use of data bases
• Targeted studies
• Hypothesis testing when appropriate

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Vaccine Safety Who Should Do It?

• Functions of vaccine promotion and safety
  evaluation need to be separate
• Need to be transparent and public
• Free of politics
• Should not reside in CDC
• Should be free of political meddling
• And seen to be
• Should have an independent reporting structure

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Vaccine SafetyWho Should Do It?

• Needs an independent home and review
• IOMTransparency?
• Needs to maintain public confidence
• Vaccines are critical to public health
• Critical to maintain confidence in safety review
• Critical that public trusts those who speak on
  vaccine safety

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Vaccine Safety

• Maintaining the publics trust is key
• Ongoing and public review of safety
• Clear action plans
• Public discussion of risk/benefit