on the effectiveness and the ideal dose of the vaccine. Vaccines determined to be safe and efficacious then advance to phase III trials, which focuses on the efficacy of the vaccine in hundreds to thousands of volunteers. This phase can take several years to complete and researchers use this opportunity to compare the vaccinated volunteers to those who have not been vaccinated to highlight any true reactions to the vaccine that occur. If a vaccine passes all of the phases of testing, the manufacturer can then apply for license of the vaccine through the FDA. Before the FDA approves use in the general public, they extensively review the results to the clinical trials, safety tests, purity tests, and manufacturing methods and establish that the manufacturer itself is up to government standards in many other areas. However, safety testing of the vaccines never ends. After FDA approval, the FDA continues to monitor the manufacturing protocols, batch purity, and the manufacturing facility itself. Additionally, most vaccines also undergo phase IV trials, which monitors the safety and efficacy of vaccines in tens of thousands of people, or more, across many years. This allows for delayed or very rare reactions to be detected and evaluated. Side effects The Centers for Disease Control and Prevention (CDC) has compiled a list of vaccines and their possible side effects. The risk of side effects varies from one vaccine to the next, but below are examples of side effects and their approximate rate of occurrence with the diphtheria, tetanus, and acellular pertussis (DTaP) vaccine, a common childhood vaccine. Mild side effects (common) Mild fever (1 in 4) Redness, soreness, swelling at the injection site (1 in 4) Fatigue, poor appetite (1 in 10) Vomiting (1 in 50) Moderate side effects (uncommon) Seizure (1 in 14,000) High fever (over 105 °F) (1 in 16,000) Severe side effects (rare) Serious allergic reaction (1 in 1,000,000) Other severe problems including long-term seizure, coma, brain damage have been reported, but are so rare that it is not possible to tell if they are from the vaccine or not. Certain vaccines have had adverse outcomes identified after being used in mass vaccination programs: In 1976 in the United States, a mass a swine flu vaccination programme was discontinued after 362 cases of Guillain–Barré syndrome among 45 million vaccinated people. William Foege of the CDC estimated that the incidence of Guillain-Barré was four times