FDA/Industry Statistics Workshop 2005

Parallel Session 6: Vaccine Trials

10:10 am – 11:30 am, Sept. 16, 2005

Co-Chairs:

Jingyee Kou (CBER), William Wang (Merck)

Panelists:

FDA Statistician: Dale Horne (CBER)Academia Statistician: Lawrence Moulton (Johns Hopkins)Industry Statistician: Joseph Heyse (Merck)FDA Clinician: Douglas Pratt (CBER)Industry Clinician: Jill Hackell (Wyeth)

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Outline

Vaccine Safety (1 topic)

Vaccine Efficacy (3 topics)

Vaccine Immunogenicity (3 topics)

Other (1 topic)

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Vaccine Safety Topic

Trial design for pre-licensure and post-licensure study

Large safety trial to detect rare adverse reaction. How rare should the event be in the interest of the public health: e.g., 1/1,000 or 1/10,000?

Long term safety trial to evaluate potential events with a long-latency pre-licensure (active reporting) versus post-licensure (voluntarily reporting, e.g VAERS )

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Vaccine Efficacy Topic 1

Estimation of indirect and total effects of vaccine

Simple randomization vs Group randomization

How should group randomization be used in vaccine development?

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Vaccine Efficacy Topic 2

Superiority vs super-superiority

Study Hypothesis on Vaccine Efficacy (VE) is

H0: VE<=0 vs H1: VE > 0

When is it enough for the lower limit 0 of the 95% CI to be 0 or close to 0, and when should it be set higher?

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Vaccine Efficacy Topic 3

How to evaluate vaccine effect on the incidence (randomized comparison) and severity (non-randomized comparison)?

Vaccine might reduce the incidence of disease moderately, while reducing severity of the disease among breakthrough cases

How should one assess the vaccine efficacy on both the incidence and the severity?

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Vaccine Immunogenicity Topic 1

Vaccine approval based only on immunogenicity

Vaccine may induce strong immune responses that have not been demonstrated as correlates of protection

Under what conditions is it appropriate to approve a vaccine based solely on immunogenicity?

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Vaccine Immunogenicity Topic 2

Selection of immunologic markers and non-inferiority margins

What’s proper methodologies to establish immune responses (e.g, antibody level) as correlates of vaccine efficacy?• Regression Analysis• Proportion Explained• Discriminant Analysis

What factors should be considered in choosing delta (e.g. 10% vs 15% percentage difference on sero-response rate)?

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Vaccine Immunogenicity Topic 3

Immunogenicity evaluation with multiple serotypes

Combination vaccine containing multiple serotypes

How should one evaluate non-inferiority for all components?

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Other Topic

Accelerated development strategy in vaccine development

Critical path initiative for vaccine development

How should one apply adaptive designs and Bayesian techniques in vaccine development?