Vaccine efficacy and effectiveness

Vaccine efficacy: 

Vaccine efficacy- % reduction in disease incidence in a vaccinated group compared to an unvaccinated group under optimal conditions 

Reduction in the chance or odds of developing clinical disease after vaccination relative to the chance or odds when unvaccinated. Vaccine efficacy measures direct protection (i.e. protection induced by vaccination in the vaccinated population sample). WHO

Reduction in the chance of developing the disease after vaccination relative to the chance in unvaccinated as determined in a prospectiverandomised controlled study. EMA

The ability of a vaccine to provide protection against disease under ideal circumstances (e.g. during a clinical trial). CDC

Vaccine effectiveness: 

Vaccine effectiveness- ability of vaccine toprevent outcomes of interest in the “real world”

The protection conferred by vaccination in a certain population.
Measures direct and indirectprotection (i.e. protection to non- vaccinated persons). WHO

Direct (vaccine induced) andindirect (population related) protection during routine use, estimated from observationalcohort studies. EMA

The ability of a vaccine to provide protection against disease when used under field conditions(routine practice). CDC

Vaccine impact: 
Compares the burden of disease caused by the pathogen included in the vaccine, in a population that has received the vaccine, to the burden of disease in a population that has not received the vaccine.

Vaccine effects
 Direct effect:
    Protection in vaccinated persons only
    Induced by individual vaccination
 Indirect effect:
    Effect of a vaccination programme
    At population level, including non-vaccinated

Direct effect
 Depends on vaccine and host characteristics Compares disease in vaccinated to disease in
and unvaccinated in one population Measured in clinical trials or in real life

Efficacy: protection measured in clinical trials Ideal conditions of administration Selected subjects (e.g. underlying diseases often excluded)

Effectiveness: protection if measured in real life situation
  Routine vaccination, including incomplete schedule, delayed administration
  Any person of the target group

Herd effects or indirect: 

Effect of widespread vaccination: protection by reduced transmission in the population, when large proportions are vaccinated

Two vaccine exposures
 Individual vaccination 
 Vaccination programme Direct effect only Direct + indirect efect

Effect of programme -> sum of effects of vaccination on vaccinated
• If there is an indirect effect

How to measure vaccine effects?

*Halloran et al

Direct effect: Direct effect of vaccination on those vaccinated

•   Exposure = individual vaccination
•   Vaccinated vs. non vaccinated, same population 
  
  Methods: study design must cancel the indirect effect of programme:
  cohortstudies (from same population)
    case control studies #      
    screening methods #
    Broome method #
  
  # Controls have same exposure/coverage than population giving rise to cases
  
  
  
  Indirect, total and overall effect
  
  Comparing two separate but similar populations, one with vaccination, the other without:
   Vaccinated persons: total effect
   Non-vaccinated: indirect effect
   All persons: overall effect
  Design:
  

  •   Population separated by time or place
      Pre and post-vaccine comparison (time)
  •   Cluster randomized trials
    
    
      Statistical or mathematical modelling

           Exposure here is programme

Impact of vaccination programme

WHO: correspond to overall effectVaccination programme
Total population being compared

Major confusion: direct and overall

Direct effect	Overall effect
of individual vaccination	of a vaccination programme
on vaccinated persons	in a population, in which a fraction only is vaccinated
Pre or post-licensure	Post-licensure only
Does not include indirect effect	Direct + indirect effects Potentially replacement disease
Compares groups from same population Need to know vaccine status	Compares 2 populations No need to know vaccine status