Response to the National Vaccine Advisory Committee Recommendations on the Immunization Safety Office Scientific Agenda

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Response to the National Vaccine Advisory
Committee Recommendations on theImmunization
Safety Office Scientific Agenda

• Frank DeStefano, MD, MPH
• Immunization Safety Office

• "The findings and conclusions in this report are
  those of the author(s) and do not necessarily
  represent the official position of the Centers
  for Disease Control and Prevention

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Overview
Background on ISO Scientific Agenda Update on
ISO Response to NVAC Recommendations
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Background on ISO Scientific Agenda
In February 2005, IOM recommended a
subcommittee of NVAC National Vaccine Advisory
Committee that includes representatives of a
wide variety of stakeholders review and provide
advice on the VSD research plan the group should
meet publicly and allow interested persons to
observe the process and provide input through
established mechanisms.
Vaccine Safety Research, Data Access, and Public
Trust, available at http//www.nap.edu/catalog/112
34.html,
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Background on ISO Scientific Agenda

• ISO/CDC developed a draft Scientific Agenda (Jan
  07 -Jan 08) 3 meetings with input from external
  consultants, federal scientists, vaccine
  manufacturers, partners, scientific literature
  and other sources
• CDC/ISO requested NVAC undertake and coordinate a
  scientific review of ISOs draft Scientific
  Agenda (July 9, 2007) and advise on
• Content of draft ISO Scientific Agenda
• Prioritization of scientific topics and
• Identify possible scientific barriers to
  implementing the Scientific Agenda
• NVAC formed the Vaccine Safety Working Group to
  review ISOs draft Scientific Agenda (April 2008
  - May 2009). This group made 32 recommendations
  in 3 categories General, Capacity, and Research
  recommendations
• On July 29, 2009, the HHS Assistant Secretary for
  Health sent the NVAC recommendations to CDC .

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Overview of ISO Response to NVAC Recommendations

• ISO has or will implement many of the NVAC
  recommendations
• Also working with NVPO to consider best way to
  address those that are beyond the scope of
  ISO/CDC.
• Today ISO will present draft responses to
  selected recommendations, focusing on the ISO/CDC
  role.
• Considerations in developing response include
• resources
• feasibility
• change in circumstances (events on the ground)
  and
• alignment with CDC and ISO mission
• Harmonize ISO Scientific Agenda with the National
  Vaccine Plan (Chapter 2)

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Current ISO Efforts Related to the Recommendations

• ISO had activities underway prior to the
  development of the Scientific Agenda that
  addressed some recommendations
• ISO has begun implementing activities to address
  the majority of the 17 general and capacity
  building recommendations
• ISO has begun or implemented some of the15
  specific recommendations including
• Metabolic/mitochondrial studies
• 3 research questions prioritized by NVAC

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Recommendation 1

• NVAC recommends ISO develop the research topic
  sections of Vaccines and Vaccination Practices,
  Special Populations, and Clinical Outcomes to
  consist of testable research questions that can
  be prioritized.
• ISO supports implementing this Recommendation
• Other agencies also may have a role in this area

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Response to Recommendation 1

• ISO will generate a list of testable hypothesis
  that could be prioritized according to the
  following considerations
• New vaccines
• Vaccines with expanded recommendations
• Potential signals for risks after vaccines
  identified in pre-licensure studies, VAERS or by
  other bodies such as IOM that have not been
  adequately studied
• Vaccines for special populations (those who may
  have different risks for adverse events than the
  general population, e.g., pregnant women)
• Questions from the current IOM safety review
  sponsored by HRSA and CDC to update 8 vaccines in
  the Vaccine Injury Table
• Priorities in the updated National Vaccine Plan
  (i.e., Chapter 2 on immunization safety)
• Specific high priority hypotheses identified in
  the NVAC Recommendations on ISOs draft
  Scientific Agenda

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Recommendation 2

• NVAC recommends periodic external review of VSD
  and CISA research and the ISO Scientific Agenda
  more broadly.
• ISO supports implementation of this
  recommendation

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Recommendation 5

• To prepare for mass vaccination use of vaccines
  not traditionally given to the civilian
  population, the NVAC recommends ISO research in
  advance approaches to safety monitoring,
  including the extent to which they would be used
  off-label or in new populations.
• This recommendation has been partially
  implemented

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Recommendation 6

• In order to better understand the biological
  mechanisms of action responsible for adverse
  events following immunization, the NVAC
  recommends that ISO should coordinate with other
  agencies to support basic research into such
  mechanisms and that CISA should conduct clinical
  research on the pathophysiologic basis of adverse
  events.
• ISO supports the need for research in this area

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Recommendation 7

• NVAC endorses the Writing Groups recommendation
  for an external expert committee, such as the
  Institute of Medicine, with broad methodological,
  design, and ethical expertise to consider
  strengths and weaknesses, ethical issues and
  feasibility including timelines and cost of
  various study designs to examine outcomes in
  unvaccinated, vaccine delayed and vaccinated
  children and report back to the NVAC.
• ISO/CDC and NVPO are working on implementing
  this recommendation

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Recommendation 9

• NVAC recommends ISO have an active role in risk
  communications research.
• This is an agency-wide priority in which CDC and
  ISO are actively engaged

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Recommendation 10

• NVAC recommends ISO identify and evaluate ways to
  (1) increase the number of serious events
  reported to VAERS and (2) improve the quality
  and completeness of reports received.
• This recommendation has been partially
  implemented during the H1N1 response

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Recommendation 11

• NVAC recommends ISO evaluate approaches to follow
  up individuals reported to VAERS with rare or
  unusual adverse events for further study,
  including the collection of biological specimens,
  when appropriate
• Activities regarding this recommendation are
  ongoing

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Recommendation 17

• NVAC recommends ISO include the vaccination of
  children with mitochondrial disease,
  mitochondrial dysfunction, and other metabolic
  diseases as a priority scientific area for
  research to develop clinical guidance
• Activities regarding this recommendation are
  ongoing

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Next Steps

• ISO will finalize the Scientific Agenda taking
  into consideration the NVAC recommendations
• ISO/CDC will provide a written response to NVAC
  and the HHS Assistant Secretary for Health
  specifying changes to the agenda and responses to
  the NVAC recommendations

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Additional Slides
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Summary of Recommendations

• General Recommendations Capacity
  Recommendations
• 1.The NVAC recommends ISO develop the research
  topic sections of Vaccines and Vaccination
  Practices, Special Populations, and Clinical
  Outcomes to consist of testable research
  questions that can be prioritized.
• 2. The NVAC recommends periodic external review
  of VSD and CISA research and the ISO Scientific
  Agenda more broadly.
• 3.The NVAC recommends ISO regularly engage the
  public and stakeholders as ISO conducts research,
  interprets the findings from their studies, and
  revises their research agenda.
• 4. the NVAC recommends CDC perform case studies
  of past decision making processes related to
  vaccine safety issues to identify lessons learned
  regarding the use of scientific data in decision
  making.
• 5. To prepare for mass vaccination use of
  vaccines not traditionally given to the civilian
  population, the NVAC recommends ISO research in
  advance approaches to safety monitoring,
  including the extent to which they would be used
  off-label or in new populations.
• 6. In order to better understand the biological
  mechanisms of action responsible for adverse
  events following immunization, the NVAC
  recommends that ISO should coordinate with other
  agencies to support basic research into such
  mechanisms and that CISA should conduct clinical
  research on the pathophysiologic basis of adverse
  events.

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Summary of Recommendations

• General Recommendations Capacity
  Recommendations
• 7.The NVAC endorses the Writing Groups
  recommendation for an external expert committee,
  such as the 7.The NVAC endorses the Writing
  Groups recommendation for an external expert
  committee, such as the Institute of Medicine,
  with broad methodological, design, and ethical
  expertise to consider strengths and weaknesses,
  ethical issues and feasibility including
  timelines and cost of various study designs to
  examine outcomes in unvaccinated, vaccine delayed
  and vaccinated children and report back to the
  NVAC.
• 8. The NVAC recommends that ISO studies are
  designed and adequately powered to assess the
  role of differences in race/ethnicity and gender
  when appropriate.
• 9. The NVAC recommends ISO have an active role in
  risk communications research.
• 10. The NVAC recommends ISO identify and evaluate
  ways to (1) increase the number of serious events
  that are reported to VAERS and (2) improve the
  quality and completeness of the reports received.
  
• 11. The NVAC recommends ISO evaluate approaches
  to follow up individuals reported to VAERS with
  rare or unusual adverse events for further study,
  including the collection of biological specimens,
  when appropriate.
• 12. The NVAC recommends that the ISO Scientific
  Agenda specify the laboratory capacity needed for
  vaccine safety research and identify potential
  collaborations with other Federal agencies or
  private entities for those areas where CDC/ISO
  lacks capacity. For the laboratory capacity that
  CDC/ISO currently possesses, ISO should request
  input from external experts to advise on the
  ongoing work and development of new laboratory
  methodologies.

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Summary of Recommendations Continued

• General Recommendations Capacity
  Recommendations
• 13. The NVAC recommends ISO study molecular
  immune responses to vaccinations, including
  common adverse events such as fever or rash, as
  subclinical correlates that might predict severe
  adverse events.
• 14. he NVAC recommends ISO create an expert
  advisory group on genomics and vaccine safety to
  assist with developing a focused genomics
  research agenda and protocol development.
• 15. The NVAC recommends ISO focus Brighton
  Collaboration research efforts on the adequacy of
  the case definitions and their usefulness in
  ongoing safety research conducted by VSD and
  other groups.
• 16. The NVAC recommends ISO create a single
  written guide dedicated to comprehensive clinical
  guidance, including identification, reporting,
  and treatment, for vaccine adverse events.
• 17.The NVAC recommends ISO include the
  vaccination of children with mitochondrial
  disease, mitochondrial dysfunction, and other
  metabolic diseases as a priority scientific area
  for research to develop clinical guidance.

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Recap of Summary of Recommendations
Research Needs Recommendations 18-32 focus on specific research questions or editorial comments Three priority questions have been addressed