Clinical trials usually progress through a series of steps or phases. Nearly all clinical trials must progress through the first three phases before approval is granted by the U.S. Food and Drug Administration (FDA). The fourth clinical trial phase evaluates long-term effects and cost-effectiveness in treatments that have received approval from the FDA to be sold to the public.
Phase I trials are the first research studies on human subjects. In these trials, a new treatment is tested in a small group of people (usually 20-80) in order to evaluate its safety, determine the range of safe dosage, and identify possible side effects. Depending on the treatment, people who volunteer for Phase I trials may be either healthy or suffering from the disease for which the treatment has been developed. Researchers use information from Phase I studies to design Phase II studies.
Once Phase I trials have demonstrated that a treatment is safe, Phase II trials are conducted to show how effective the treatment is. The treatment is given to a larger group of people (usually 100-300) to determine its efficacy and to further evaluate its safety. Researchers give the treatment to participants with the disease or condition of interest, as well as control groups that are closely monitored during Phase II trials.
After Phase I and Phase II studies show evidence that the treatment is effective, then Phase III trials can begin. In Phase III trials the treatment is given to participants to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information so that the treatment will be used safely. Several hundred to several thousand participants may be enrolled. At the conclusion of a well designed Phase III trial, the new treatment will be found to be inferior, equivalent, or superior to the standard, commonly used treatment. If the trial demonstrates that the new treatment is superior to the standard, researchers submit detailed results from the trial to the FDA which determines whether the treatment provides a clinical benefit and should be approved.
Even after the FDA approves a new treatment, it will continue to be monitored through long-term studies—and its cost-effectiveness will continue to be evaluated. Phase IV studies concentrate on gathering additional information about the new treatment’s risks, benefits, and optimal use. If dangerous side effects are found during these post-approval trials, the new treatment is taken off of the market.