Trial Designs and Endpoints: What would it take to license a new vaccine What would it take to recom

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Trial Designs and Endpoints What would it
take to license a new vaccine? What would it
take to recommend a major new use for a licensed
vaccine?

• Steven Black, MD
• Kaiser Permanente Vaccine Study Center

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Adult are Different Pneumococcal Trial Issues

• In pediatric trials, there was no licensed
  recommended vaccine for infants.
• In pediatric trials, the target population was
  naïve to the antigens.
• Pneumonia is the primary public health target in
  the adult population versus invasive disease in
  children
• Effectiveness (CAP) versus efficacy (Invasive
  Disease)
• Correlates of protection based on invasive
  disease in children are difficult to extrapolate
  to respiratory disease in adults.

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Trial Design Issues

• Outcomes CAP, pneumonia with a positive sputum,
  pneumonia with a positive blood culture, invasive
  disease.
• What is the role of PCR or indirect techniques?
• Comparison group unvaccinated, standard practice
  for polysaccharide (adjusting for time since
  vaccination), polysaccharide.
• For outcomes with an isolate, is the outcome
  serotype specific disease or overall impact.
• Age of target population

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A Spectrum of Possible Scenarios
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Goals of This Session

• Understand possible trial designs and their
  advantages and disadvantages.
• Understand the statistical approach to various
  designs and endpoints.
• Discuss the feasibility of various trial designs
• Discuss what might be acceptable to license a new
  vaccine or obtain a new vaccine indication from
  the FDA perspective.
• Discuss possible next steps.

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Session Overview Trial Designs and Endpoints 

• Brian Plikaytis Statistical considerations,
  non-inferiority, Correlates of protection
•  Jill Hackell Clinical Issues in Trial Design
  for a new pneumococcal vaccine. 
• Robert Kohberger Specificity versus
  Sensitivity Tradeoffs in Choice of Outcomes
• Carl Frasch FDA research and viewpoint on
  endpoints for licensure.  
• Douglas Pratt FDAs viewpoint on design of
  trials for licensure of new vaccines and
  establishment of new indications for currently
  licensed vaccines.