Epi corner - May 2015

1. The concepts of vaccine efficacy and effectiveness are important to differentiate.
   
   Vaccine efficacy relates to the "best case scenario" of vaccine protectiveness under controlled conditions. They are best measured by double-blinded, randomized controlled clinical trials. In this type of study, individuals are randomly assigned to either a group that is given the vaccine or to a second group that is given a placebo, and researchers and participants are not aware of which they receive. Vaccine efficacy trials are commonly required before a new vaccine is licensed by a regulatory authority, such as the Therapeutic Goods Administration (TGA) of Australia.
   
   Vaccine effectiveness, on the other hand, relates to the "real world" view of how a vaccine (which may already have proved to have high vaccine efficacy) reduces disease in a population. It is a useful way to assess the net balance of benefits and adverse effects of a vaccination program, not just the vaccine itself, under more natural field conditions rather than in a controlled clinical trial.
   
   One of the commonest ways of measuring this is by conducting a retrospective case control study, where the rates of vaccination among a set of infected cases are compared to appropriate uninfected controls, and an odds ratio for developing infection despite vaccination, is calculated.
2. Clinical trials, including vaccine trials are conducted in a series of steps, called phases and each phase is designed to answer a separate research question.
   • Phase I: These are usually small-scale trials (approximately 10 - 100 participants) to assess whether the vaccine is safe in humans and see what immune response it evokes. A safe dosing range and possible side-effects can also be determined.
   • Phase II: The vaccine is given to a larger group of people to see if it is effective and to further evaluate its safety.
   • Phase III: The vaccine is studied on an even larger scale (1000 - 10, 000 participants) across several sites to confirm its effectiveness, monitor side effects, and collect information that will allow the vaccine to be used safely. If the vaccine retains safety and efficacy over a defined period, the manufacturer will be able to apply to the regulatory authorities for a licence to market the product for human use.
   • Phase IV: These studies are done after the vaccine has been licensed and introduced for use. This stage aims to detect rare adverse effects and assess any side effects associated with long-term use.

References:

1. Weinberg GA and Szilagyi PG, Vaccine Epidemiology: Efficacy, Effectiveness and the Translational Research Roadmap. Journal of Infectious Diseases 2010; 201: 1607 - 1610.
2. Comstock GW, Evaluating vaccination effectiveness and vaccine efficacy by means of case-control studies. Epidemiological Reviews 1994; 16 (1): 77-89.
3. WHO Vaccine safety basics - Pre licensure vaccine safety, accessed 20th April 2015; available from: https://openwho.org/courses/vaccine-safety-basics.