Establishing and Changing Vaccination Schedules

1
Establishing and Changing Vaccination Schedules

• Vaccine Development and Supply Subcommittee

2
How are Schedules Established and Changed?

• Vaccination schedules in the U.S. are based on
  results of pre-licensure trials and the schedule
  submitted by manufacturers and approved by FDA
• Post-licensure, data may be generated suggesting
  that more or fewer doses may be better
• Questions to address
• What infrastructures exist that can generate data
  assessing vaccination schedules?
• How can these data be used to potentially lead to
  schedule changes?

3
What are the potential benefits of changing
vaccination schedules?

• Potential value of more parsimonious schedules
• Fewer injections
• Fewer adverse events
• Lower costs
• Less stress to vaccine supply
• Potential risks
• Less effective disease prevention
• May not be consistent with scheduled visits or
  combination vaccines
• May be confusing to providers and parents

4
Infrastructures and experience from the U.K.

• Recent changes in the U.K. vaccination schedule
• 3-dose PCV vaccination (2 during infancy and a
  1-yr booster)
• Dropped one infant Men C conjugate dose and added
  a 1-yr booster
• Added a Hib booster to a 3-dose infant schedule
• Data contributing to decision-making
• Immunogenicity data
• Surveillance data

5
Infrastructures contributing data to UK vaccine
schedule decisions

• Health protection agency
• Scientific institute funded by government (arms
  length)
• Responsible for surveillance and epidemiological
  studies including vaccine safety
• Vaccine evaluation consortium
• Independent agency
• Interacts with NIBSC (regulatory agency)
• Mission to research near term vaccines
• Immunogenicity studies
• Clinical trials

6
Establishing and changing vaccination schedules
in the U.K.

• Recommendations made by the Joint Committee on
  Vaccines and Immunization
• Flexibility in establishing and changing
  schedules
• EU licensure allows varying schedules that fit
  with different vaccination schedules of member
  states
• HPA and consortium data contribute to Joint
  Committee decisions to establish and change
  schedules
• Joint Committee has recommended off label use

7
Changing vaccination schedules the PCV example

• Data on PCV vaccination generated since U.S.
  licensure
• Immunogenicity of 2 or 3 infant doses and a
  booster
• Impact of vaccination on invasive disease
• Ecological studies (trends based on surveillance
  data)
• Case control efficacy studies including of
  various number of doses and schedules
  (facilitated by the vaccine shortage leading to
  many children receiving fewer than a full 4 dose
  schedule)
• Impact of vaccination on carriage
• Different vaccination schedules adopted elsewhere
  (2 1 schedule in the UK and Quebec)

8
Perspectives of HHS agencies on changing
vaccination schedules (1)

• Effective disease prevention is the highest
  priority
• Very high bar to assure that an alternate
  schedule is as effective
• Immunogenicity studies may contribute to schedule
  decisions
• Especially where there is a good correlate of
  protection or ability to bridge to results of
  prior randomized trials
• Epidemiological studies and surveillance results
  contribute but concern about potential for bias
• Randomized clinical trials remain important

9
Perspectives of HHS agencies on changing
vaccination schedules (2)

• U.S. infrastructures for evaluating vaccines
• NIH Vaccine Treatment and Evaluation Units
• CDC surveillance and epidemiological studies
• No suggestions by agency representatives for
  additional infrastructure needs
• U.S. process to consider vaccination schedule
  changes
• Schedule recommended by the Advisory Committee on
  Immunization Practices
• FDA licensed schedule provides strong guidance

10
Bottom line

• Robust discussion of establishing and changing
  schedules
• No recommendations from HHS agencies on changes
  to facilitate evaluation or potential
  modification of vaccination schedules
• NIH contract for large-scale 2/4 immunogenicity
  and safety studies done in the past and may be an
  approach to generate added data
• No current recommendation for further
  consideration by NVAC

11
Subcommittee topic 2 Priorities for vaccine
development and research

• NIH proposed that the subcommittee collaborate in
  planning a meeting to discuss vaccine research
  priorities to contribute to the revision of the
  National Vaccine Plan
• Subcommittee discussed the value of analyzing
  vaccine development priorities
• Priorities assessed by IOM (1985 and 2000)
• Did they have an impact?
• Would further work from a public health
  perspective contribute to vaccine development?
• Directly stimulate industry R D
• Lead to more clear signals from government