An Analytical Framework for Immunization Programs

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An Analytical Framework for Immunization Programs

• Will it work for the new vaccines?
• June 12, 2007
• Tim Hilderman, MD FRCPC

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L.J. Erickson et al

• Published a paper in the journal Vaccine entitled
  An analytical framework for immunization
  programs in Canada
• Vaccine 23 (2005) 2470-2476
• Contacted key scientific and public health
  experts involved in immunization programs across
  Canada
• Questionnaire methodology used to determine
  important factors in their recent decisions
  regarding publicly funded immunization programs

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Objectives

• Describe an analytical framework for immunization
  programs
• Utilize the framework in the evaluation of
  Gardasil as a potential addition to publicly
  funded vaccine program
• Evaluate the usefulness of the framework

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Vaccines Are

• highly regulated, complex biologic products
  designed to induce a protective immune response
  both effectively and safely
• National Advisory Committee on Immunization
  (NACI), Canadian Immunization Guide, Seventh
  Edition

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Vaccines are also

• Enjoying substantial, renewed interest on the
  part of a biopharmaceutical industry that had
  previously looked at the vaccine business as
  mature and low margin.
• AstraZeneca to acquire MedImmune for 58 per
  share in a fully recommended, all-cash
  transaction with a total enterprise value of
  15.2 billionThe acquisition extends
  AstraZeneca's RD science base to allow it to
  address novel drug targets through 3 key
  technological approaches small molecules,
  biologics and, for the first time, vaccines
  April 23, 2007
• Why? In part because societal response to
  threats such as bioterrorism, avian influenza,
  pandemic influenza all involve vaccine as an
  integral part of the response -

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Why Do We Need A Framework?
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Doesnt Health Canada or NACI Do this??

• Prior to being given market authorization, a
  manufacturer must present substantive scientific
  evidence of a product's safety, efficacy and
  quality as required by the Food and Drugs Act and
  Regulations.
• NACI determines the optimal conditions of use of
  a given vaccine in the epidemiological context of
  Canada

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But whose job is it to integrate new vaccine
technologies?
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The Framework

• Burden of disease
• Vaccine Characteristics
• Immunization Strategy
• Cost-effectiveness
• Acceptability
• Feasibility
• Ability to Evaluate
• Research Questions
• Equity/Ethics/Legalities/Conformity/Politics

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GARDASIL

• Quadrivalent vaccine consisting of L1 capsid
  protein of HPV types 6,11, 16, and 18.
• Gene encoding L1 protein of each is expressed in
  the yeast (Saccharomyces cerevisieae)
• The protein product self-assemble into a
  non-infectious virus like particle (VLP)
• VLPs are purified and adsorbed onto aluminum
  containing adjuvant
• 3 doses 0, 2, and 6 months, intramuscular into
  deltoid or anterolateral upper thigh

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1. Burden of Illness

• Does the burden of disease justify a control
  program?
• Incidence
• Prevalence
• Clinical manifestations and complications
• Specific populations at risk
• Social Impact (quality of life)
• Economic Impact

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Human HPV infection

• HPV can cause benign and cancerous anogenital
  disease
• Anogenital HPV infections are transmitted
  sexually by direct epithelial to epithelial
  contact
• Cervical dysplasia and cancer are potential
  consequences of genital infection with High Risk
  (HR) oncogenic HPV subtypes
• HPV 16 and 18 contribute to 70 of cervical
  cancers
• HPV 6 and 11 cause 90 of genital warts

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Human HPV Infection

• HPV infection extremely common prevalence
  3-42 depending on age group
• In female university students (mean age 23 years)
  cumulative rate was 36 over 24 months.
• 75 of female pop. have been or will be infected
  with HPV (lifetime)
• Many resolve some persist and cause precancerous
  lesions and cancer
• 1 million women, 250 000 deaths world wide
  annually (2005)
• Estimated 1300-1400 Cdn women per year diagnosed
  with cervical cancer, 400 deaths

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2.Vaccine Characteristics

• Do the characteristics of the vaccine permit
  implementation of an effective and safe
  immunization program?
• Nature and characteristics of imm. Agent
• Vaccine Supply
• Administration Schedule
• Efficacy
• Safety

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Gardasil Efficacy

• Primary Endpoint prevention of HPV 16 and 18
  related cervical intraepithelial neoplasia (CIN)
  2/3 and adenocarcinoma in situ (AIS) at 36
  months 100
• Vaccine group n9342, CIN 2/3 or AIS0
• Placebo group n 9400 CIN2/3 or AIS111
• Primary Endpoint prevention of persistent
  HPV-6,11,16, 18 was 89 at 30 months

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Gardasil

• Safety safe and well tolerated based on 11640
  vaccine recipients
• local injection site reactions pain, redness,
  swelling,
• systemic reactions fever, nausea, dizziness,
  diarrhea similar to placebo
• 5 serious events among 11 640 vaccine recipients
  bronchospasm (poss.) gastroenteritis (poss),
  headache/hypertension (def), vag hem (prob),
  injection pain/movement impairment (prob)
• Contraindicated in persons with history of
  hypersensitivity to yeast or other vaccine
  components

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3. Immunization Strategy

• Is there an immunization strategy which allows
  goals of the control program to be attained?
  Existing Strategies?

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Universal? Target? High Risk?
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4. Cost Effectiveness

• Is it possible to obtain funding for the program
  and are cost-effectiveness indices comparable to
  those of other health care interventions?
• Requires economic analysis-Cost (135/dose
  X3405)
• Cost per year of life saved?
• Cost per case of cervical cancer prevented?
• Opportunity Costs
• Gardasil Studies ongoing

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5. Acceptability
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6. Feasibility

• Is program implementation feasible given existing
  resources
• The best immunization strategy has no
• value if impossible to carry out in practice
• Vaccine supply
• Funding Fed vs Provincial
• Integration with existing programs

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NACI Statement Feb 15 2007

• Females between 9 and 13 years of age
• before onset of sexual intercourse for most
  canadian females
• Females between 14 and 26
• even if sexually active they may not yet have HPV
  infection and unlikely to have been infected with
  all 4
• Females (14-26) with previous abnormal pap,
  cervical cancer or genital warts
• Similar rationale to above
• Females gt26/Femaleslt9/Males
• Studies ongoing, no recommendation to date

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7. Ability to Evaluate

• Can the various aspects of the program be
  evaluated?

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8. Research Questions

• Have important research questions affecting
  implementation for the program been adequately
  addressed
• Immunogenicity of 2 doses?
• Impact on cervical screening?
• New vaccines on horizon ie. Cervarix

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9. Equity

• Is the program equitable in terms of
  accessibility of the vaccine for all target
  groups?

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10. Ethical Considerations

• Have ethical concerns regarding implementationof
  the immunization program been adequately
  addressed?

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11. Legal Considerations

• Have legal concerns regarding implementation been
  addressed?
• Example off label use?

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12. Conformity

• Does the planned program conform to those planned
  or implemented elsewhere?

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13. Political Considerations

• Will the proposed program be free of controversy
  and or produce some immediate political benefits?