Vaccine trial

Phase I

The Phase I study consists of introducing the vaccine candidate to assess its safety in healthy people. A vaccine Phase I trial involves normal healthy subjects, each tested with either the candidate vaccine or a "control" treatment, typically a placebo or an adjuvant-containing cocktail, or an established vaccine (which might be intended to protect against a different pathogen). The primary observation is for detection of safety (absence of an adverse event) and evidence of an immune response.

After the administration of the vaccine or placebo, the researchers collect data on antibody production, on health outcomes (such as illness due to the targeted infection or to another infection). Following the trial protocol, the specified statistical test is performed to gauge the statistical significance of the observed differences in the outcomes between the treatment and control groups. Side effects of the vaccine are also noted, and these contribute to the decision on whether to advance the candidate vaccine to a Phase II trial.

One typical version of Phase I studies in vaccines involves an escalation study, which is used in mainly medicinal research trials. The drug is introduced into a small cohort of healthy volunteers. Vaccine escalation studies aim to minimize chances of serious adverse effects (SAE) by slowly increasing the drug dosage or frequency. The first level of an escalation study usually has two or three groups of around 10 healthy volunteers. Each subgroup receives the same vaccine dose, which is the expected lowest dose necessary to invoke an immune response (the main goal in a vaccine – to create immunity). New subgroups can be added to experiment with a different dosing regimen as long as the previous subgroup did not experience SAEs. There are variations in the vaccination order that can be used for different studies. For example, the first subgroup could complete the entire regimen before the second subgroup starts or the second can begin before the first ends as long as SAEs were not detected. The vaccination schedule will vary depending on the nature of the drug (i.e. the need for a booster or several doses over the course of short time period). Escalation studies are ideal for minimizing risks for SAEs that could occur with less controlled and divided protocols.

Phase II

The transition to Phase II relies on the immunogenic and toxicity results from Phase I in a small cohort of healthy volunteers. Phase II will consist of more healthy volunteers in the vaccine target population (~ hundreds of people) to determine reactions in a more diverse set of humans and test different schedules.

Phase III

Similarly. Phase III trials continue to monitor toxicity, immunogenicity, and SAEs on a much larger scale. The vaccine must be shown to be safe and effective in natural disease conditions before being submitted for approval and then general production. In the United States, the Food and Drug Administration (FDA) is responsible for approving vaccines.

Phase IV

Phase IV trials are typically monitor stages that collect information continuously on vaccine usage, adverse effects, and long-term immunity after the vaccine is licensed and marketed. Harmful effects, such as increased risk of liver failure or heart attacks, discovered by Phase IV trials may result in a drug being no longer sold, or restricted to certain uses; examples include cerivastatin (brand names Baycol and Lipobay), troglitazone (Rezulin) and rofecoxib (Vioxx). Further examples include the swine flu vaccine and the rotavirus vaccine, which increased the risk of Guillain-Barré syndrome (GBS) and intussusception respectively. Thus, the fourth phase of clinical trials is used to ensure long-term vaccine safety.