Safety assessment of adjuvanted vaccines: Methodological considerations

Figures & data

Figure 1. Effects of the movement against whole-cell pertussis vaccines on coverage and on disease epidemiology in the United Kingdom and Wales. Reprinted from The Lancet, Vol. 351, Gangarosa EJ, Galazka AM, Wolfe CR, Phillips LM, Gangarosa RE, Miller E, Chen RT, Impact of anti-vaccine movements on pertussis control: the untold story, pages 356–61, Copyright (1998), with permission from Elsevier.

Figure 2. Factors guiding assessment of adjuvanted vaccine safety:Characteristics of the target population influence initial pre-clinicalevaluations. These features, as well as the results of pre-clinical testing, guide the specific assessment of vaccine safety in clinical trials.

Figure 3. Post-licensure safety assessments are planned based on results of clinical trials, trends identified through spontaneous reports of adverse events after vaccination and field experience with the vaccine.

Figure 4. Factors potentially influencing the influence the benefit-risk profile of adjuvanted vaccines.

Table 1. Safety evaluation during the clinical development program

Phase I studies	Phase II studies	Phase III studies
• Explore the safety profile in a small number of healthy subjects	• Assess safety in several hundred of the target population	• Determine safety profile in several thousands of the target population
• Perform dose range studies of antigen and adjuvant to identify optimal dose	• Appropriate control groups	• Appropriate control groups
• Assess local symptoms and systemic symptoms immediately after immunization	• Standardized methods used for collecting safety data	• Standardized methods used for collecting safety data
• Standardized methods used for collecting safety data	• Specific safety assessments guided by characteristics of the target population	• Specific safety assessments guided by characteristics of the target population
	• Assess immunogenicity and clinical benefit of the vaccine	• Establish clinical benefit of the vaccine
	• Assess local symptoms and systemic symptoms immediately after immunization	• Assess local symptoms and systemic symptoms immediately after immunization
	• Typically 6–12 month follow-up of serious adverse events, autoimmune diseases and other adverse events of special interest	• Typically 6–12 month follow-up of serious adverse events, autoimmune diseases and other adverse events of special interest

The acceptable benefit-risk profile is established during the clinical development phase, leading to licensure of the vaccine for the target population.