A basic trial might involve forming two groups from a random sample of the target population. One group receives the vaccine while the control group receives a placebo, an adjuvant-containing cocktail or a different vaccine which might be against a totally different disease. Data on antibody production and immunity to the disease in question is collected from both groups some time after the administration of the vaccine or placebo, and a statistical test is performed on these two sets of data to determine whether or not there is any statistically significant difference between them. If the vaccine produces no statistically significant results, then it is rejected. Side effects of the vaccine are also noted, and these too contribute to the decision on whether to license it.
Methodological issues and problems
Vaccine trials may take months or years to complete, since a sufficient time period must elapse for the subjects to react to the vaccine and develop the required antibodies. Antibody production is regarded as sufficient to prove the vaccine's effectiveness, and it is rare for subjects to be exposed directly to the biological agent (usually a virus or bacteria) the vaccine is supposed to provide immunity against. Assessing the severity and likelihood of side effects in the target population is extremely difficult because of the diversity of patients and the vast number of possible interactions with other medicines and environmental factors.
In many trials, adverse effects of vaccines are actively monitored only for a short time, e.g. 14 days.
In many trials, the vaccine efficacy and safety research is not done by comparing to a group not receiving the vaccine, but to a group receiving a different vaccine for a different disease or a cocktail of vaccine additives (e.g. aluminum adjuvants) - thus the research is not designed to show and can not show real vaccine efficacy or safety.
Often the vaccine group gets the same injection (placebo, adjuvant cocktail, a different vaccine) a certain time period after the control group and vice versa, making it impossible for anyone to study the long term effects of the vaccine which is studied.