![Page 1: FDA/Industry Statistics Workshop 2005 Parallel Session 6: Vaccine Trials 10:10 am – 11:30 am, Sept. 16, 2005](https://reader036.vdocument.in/reader036/viewer/2022082917/5514bcde550346b0478b4594/html5/thumbnails/1.jpg)
FDA/Industry Statistics Workshop 2005
Parallel Session 6: Vaccine Trials
10:10 am – 11:30 am, Sept. 16, 2005
![Page 2: FDA/Industry Statistics Workshop 2005 Parallel Session 6: Vaccine Trials 10:10 am – 11:30 am, Sept. 16, 2005](https://reader036.vdocument.in/reader036/viewer/2022082917/5514bcde550346b0478b4594/html5/thumbnails/2.jpg)
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)
![Page 3: FDA/Industry Statistics Workshop 2005 Parallel Session 6: Vaccine Trials 10:10 am – 11:30 am, Sept. 16, 2005](https://reader036.vdocument.in/reader036/viewer/2022082917/5514bcde550346b0478b4594/html5/thumbnails/3.jpg)
3
Outline
Vaccine Safety (1 topic)
Vaccine Efficacy (3 topics)
Vaccine Immunogenicity (3 topics)
Other (1 topic)
![Page 4: FDA/Industry Statistics Workshop 2005 Parallel Session 6: Vaccine Trials 10:10 am – 11:30 am, Sept. 16, 2005](https://reader036.vdocument.in/reader036/viewer/2022082917/5514bcde550346b0478b4594/html5/thumbnails/4.jpg)
4
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 )
![Page 5: FDA/Industry Statistics Workshop 2005 Parallel Session 6: Vaccine Trials 10:10 am – 11:30 am, Sept. 16, 2005](https://reader036.vdocument.in/reader036/viewer/2022082917/5514bcde550346b0478b4594/html5/thumbnails/5.jpg)
5
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?
![Page 6: FDA/Industry Statistics Workshop 2005 Parallel Session 6: Vaccine Trials 10:10 am – 11:30 am, Sept. 16, 2005](https://reader036.vdocument.in/reader036/viewer/2022082917/5514bcde550346b0478b4594/html5/thumbnails/6.jpg)
6
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?
![Page 7: FDA/Industry Statistics Workshop 2005 Parallel Session 6: Vaccine Trials 10:10 am – 11:30 am, Sept. 16, 2005](https://reader036.vdocument.in/reader036/viewer/2022082917/5514bcde550346b0478b4594/html5/thumbnails/7.jpg)
7
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?
![Page 8: FDA/Industry Statistics Workshop 2005 Parallel Session 6: Vaccine Trials 10:10 am – 11:30 am, Sept. 16, 2005](https://reader036.vdocument.in/reader036/viewer/2022082917/5514bcde550346b0478b4594/html5/thumbnails/8.jpg)
8
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?
![Page 9: FDA/Industry Statistics Workshop 2005 Parallel Session 6: Vaccine Trials 10:10 am – 11:30 am, Sept. 16, 2005](https://reader036.vdocument.in/reader036/viewer/2022082917/5514bcde550346b0478b4594/html5/thumbnails/9.jpg)
9
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)?
![Page 10: FDA/Industry Statistics Workshop 2005 Parallel Session 6: Vaccine Trials 10:10 am – 11:30 am, Sept. 16, 2005](https://reader036.vdocument.in/reader036/viewer/2022082917/5514bcde550346b0478b4594/html5/thumbnails/10.jpg)
10
Vaccine Immunogenicity Topic 3
Immunogenicity evaluation with multiple serotypes
Combination vaccine containing multiple serotypes
How should one evaluate non-inferiority for all components?
![Page 11: FDA/Industry Statistics Workshop 2005 Parallel Session 6: Vaccine Trials 10:10 am – 11:30 am, Sept. 16, 2005](https://reader036.vdocument.in/reader036/viewer/2022082917/5514bcde550346b0478b4594/html5/thumbnails/11.jpg)
11
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?