Monitoring the Effectiveness of Pandemic Influenza Vaccines

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Monitoring the Effectiveness of Pandemic
Influenza Vaccines
VRBPAC, February 27, 2007 David K. Shay, MD,
MPH Epidemiology and Prevention Branch, Influenza
Division (proposed) Centers for Disease Control
Prevention
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Pandemic Vaccines Background

• Limited immunogenicity and safety data will be
  available prior to distribution of a pandemic
  vaccine
• Safety monitoring will be essential
• Post-licensure safety studies can begin with
  pre-pandemic use of each product, and continue
  throughout the vaccine program
• If desired, post-licensure immunogenicity data
  could be collected in the pre-pandemic setting

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Pandemic Vaccines Background

• Data concerning clinical effectiveness of
  pandemic vaccines will be essential
• Immunogenicity and protection from illness
  imperfectly correlated
• Different populations may receive vaccine in pre-
  and post-licensure situations
• Vaccine match, need to change strain
• But obviously must await onset of the pandemic
  and illness in populations eligible for
  vaccination

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Pandemic Vaccine Effectiveness

• Effectiveness protection against influenza
  illness when vaccine is administered in an
  immunization program
• Effectiveness may vary by age, medical history,
  and immunocompetence of patient
• Effectiveness may vary with outcomes
• Lower for non-specific illnesses that can be
  caused by pathogens other than the pandemic virus
• May vary by severity illness, hospitalization,
  need for mechanical ventilation, death
• Need to assess effectiveness after 1 and 2 doses
  of vaccine

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CDCs Existing Influenza VE Projects Base for
Pandemic VE Assessments

• Two projects build on existing surveillance
  systems for influenza
• Emerging Infections Program (EIP)
• New Vaccine Surveillance Network (NVSN)
• Project with Marshfield Clinic was funded to
  provide rapid, within season estimates of VE
  against a laboratory-confirmed outcome
• All use laboratory-confirmed influenza outcomes

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Population-Based Influenza Surveillance

• EIP 12 sites
• Children lt18 yrs hospitalized with
  laboratory-confirmed influenza infection
• Adult surveillance began January 2006
• NVSN 3 sites
• Children lt5 yrs with inpatient or outpatient
  laboratory-confirmed influenza infection
• Outpatient surveillance in 6-12 yrs started this
  season

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Emerging Infections Program Studies
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NVSN Studies
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Marshfield Clinic Studies
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Underlying Rationale for Pandemic Vaccine
Prioritization

• Everyone will be susceptible
• US-based production capacity is not currently
  sufficient to provide vaccine rapidly for the
  entire population
• Earliest doses of vaccine can be projected as
  becoming available at 20 weeks after isolation
  and characterization of the pandemic virus

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ACIP/NVAC Priority Groups

• Joint work of the two HHS committees
• Process included consideration of
• Estimates of vaccine supply and effectiveness
• Effects of pandemic by age and risk group
• Potential effects on critical infrastructure and
  health care
• Recommendations included in the 2005 HHS pandemic
  plan
• As guidance for State/local planning
• To promote further discussion

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Top 2 ACIP/NVAC Priority Groups
1.A. Vaccine and antiviral manufacturers and
others essential to manufacturing and critical
support (40,000) Medical workers and public
health workers who are involved in direct patient
contact, other support services essential for
direct patient care, and vaccinators (8-9
million) 1.B. Persons gt 65 years with 1 or more
influenza high-risk conditions, not including
essential hypertension (approximately 18.2
million) Persons 6 months to 64 years with 2 or
more influenza high-risk conditions, not
including essential hypertension (approximately
6.9 million) Persons 6 months or older with
history of hospitalization for pneumonia or
influenza or other influenza high-risk condition
in the past year (740,000)
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Interagency Pandemic Vaccine Prioritization
Working Group

• Participants from multiple federal agencies
• Consideration of ACIP/NVAC recommendations
• Consideration of National Infrastructure Advisory
  Council recommendations on critical
  infrastructure
• Public engagement meetings and stakeholder
  meeting

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Summary of 2 Public Engagement and Stakeholder
Meetings

• At each of the 3 meetings, the most highly rated
  goals were the same
• Maintaining critical societal functions
• Protecting those who would help others during a
  pandemic
• Protecting children as our future
• Most other goals were considered moderately
  important
• Including protecting those most likely to get
  sick or die during a pandemic
• Ratings and rank order varied between meetings

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Pandemic Vaccine Prioritization Interagency WG
Next Steps

• Draft prioritization guidance developed
• Public stakeholder meetings
• Written comments
• ACIP updated by Ben Schwartz, NVPO
• The working group also will consider
• Pre-pandemic vaccine prioritization
• Modifying guidance at the time of a pandemic
• Final guidance expected by May

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Monitoring Pandemic Vaccine Effectiveness 1

• Lab-confirmed outcomes will be studied
• Hospitalizations captured in several systems
• Additional more severe outcomes (e.g, all-cause
  mortality) may also be studied
• Observational studies must collect data on
  possible confounding factors
• Selection bias likely, but cannot assume
  direction
• Need to link existing individual health data to
  vaccination and outcome data

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Monitoring Pandemic Vaccine Effectiveness 2

• Plans will evolve as vaccine priorities develop
• Existing systems cover children well
• Community-based studies may not be efficient if
  initial vaccine is prioritized to a few critical
  infrastructure sectors
• Vaccine distribution and tracking methods
• State, regional registries may be used to
  identify vaccinated individuals
• Need to link pandemic vaccine receipt back to
  medical and demographic data

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Monitoring Pandemic Vaccine Effectiveness 3

• CDC will expand existing systems
• Assess effectiveness among adults in EIP system
• Rapid assessment methods in other sites
• Potential for new systems
• Consider using sentinel provider system and
  point-of-care tests being developed
• CDC will work with governmental and other
  partners to meet needs for effectiveness data

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Acknowledgments

• Emerging Infections Program sites
• CA
• CO
• CT
• GA
• OR
• TN
• Marshfield Clinic Research Foundation

• New Vaccine Surveillance Network sites
• Childrens Hospital Medical Center Cincinnati
• University of Rochester
• Vanderbilt University
• Ben Schwartz
• Joe Bresee
• Tony Fiore
• Nancy Cox

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(No Transcript)
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Basis for ACIP/NVAC Prioritization

• Primary goal to mitigate adverse health outcomes
• Pandemic severity assumptions
• 20-30 attack rate up to 1 case fatality rate
• Certain benefit of vaccinating high-risk versus
  unclear benefit of vaccinating critical
  infrastructure
• Estimate of 10-15 absenteeism due to illness or
  caring for ill family members at pandemic peak
• Much greater mortality risk among vulnerable
  persons than general population

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ACIP/NVAC Priority Groups Personnel
Cumulative Element and Tier
(1,000s) total (1,000s)
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Rationale for Reconsideration of Pandemic Vaccine
Prioritization

• Public engagement meetings
• Preserving essential services ranked as top goal
• Evolving planning assumptions
• More severe pandemic
• Evolving pandemic response strategies
• Community mitigation guidance
• Additional analysis of critical infrastructures

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EIP Surveillance Areas
California Kaiser Northern California members in
3 county San Francisco Bay area, and non-Kaiser
children aged lt2 years Colorado 5 county Denver
area Connecticut 1 county New Haven
area Georgia 8 county Atlanta area Maryland 5
county Baltimore area and Baltimore
City Minnesota 7 county Minneapolis area New
Mexico 1 county in Albuquerque area and 3 county
Las Cruces area New York 8 county Albany area
and 7 county Rochester area Oregon 3 county
Portland area Tennessee 8 county Nashville
area Total 4.7 million children aged lt18, or 7
of US population
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NVSV Surveillance Areas
Children aged lt5 years in these
communities Monroe County, New York 43,720
Davidson County, Tennessee 56,466 Hamilton
County, Ohio 44,002 Total 144,188
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Marshfield Clinic Population

• The influenza study cohort was drawn from the
  Marshfield Epidemiologic Study Area (MESA), a
  dynamic, population-based cohort of approximately
  54,000 residents living in 14 zip-codes
  surrounding Marshfield, Wisconsin
• Nearly all MESA residents receive all inpatient
  and outpatient care from Marshfield Clinic
  facilities, which use an electronic medical
  record that captures ?90 of outpatient visits,
  99 of deaths, and 95 of hospital discharges for
  the population
• The 2004-05 study cohort included 11,565 people,
  including 1,881 (16) with a clinical encounter
  for acute respiratory illness based on diagnosis
  codes in the electronic medical record during the
  12-week study period
• The 2005-06 study cohort included 18,542
  residents