The Phases of Clinical Trials

Clinical trials that test new cancer treatments involve a series of steps, called phases. Depending on the results of each phase, a treatment may move to testing in the next phase. Early phases (phases 1 and 2) test for safety, such as what the side effects are and what a safe dose is. Later phases (phases 3 and 4) compare the treatment to current standard treatments.

In short: trials move through phases, from small safety studies to large comparisons with standard care.

• Phase 1. Researchers figure out whether a new treatment is safe, what its side effects are, whether people can tolerate it, and the highest dose people can tolerate. These trials are done in a small group of people (around 15 to 30). They also make sure the treatment affects the cancer.
• Phase 2. This phase includes more people (50 to 100) to see if the new treatment seems to work against the cancer, such as by shrinking tumors or slowing their growth. Researchers continue to study safety, including short-term side effects.
• Phase 3. Researchers compare the treatment to the current standard therapy to see which works better and which has fewer side effects. Participants are randomly assigned to one of the treatments. Phase 3 trials include large numbers of people (from 100 to several thousand) to make sure the result is valid.
• Phase 4. This phase looks at long-term safety and effectiveness after a new treatment has been approved by the US Food and Drug Administration (FDA) and is available to the public. Safety and effectiveness are watched in large, diverse groups over a longer period of time.

Results from phase 1 to phase 3 trials are used to make decisions about approving new treatments, or approving existing treatments for new conditions, by agencies like the FDA.

Every clinical trial has requirements that must be met to join. These are called eligibility criteria. Common criteria address things such as your health, medical history, family medical history, risk factors, age, treatment history, and your tumor's genetic changes.

These criteria help reduce the medical differences among people in a trial, reduce the risk that people will be harmed, and limit the trial to those most likely to benefit. When people in a trial are alike in specific ways, researchers can be more certain that the results are due to the treatment being tested and not to other factors.

In short: eligibility criteria help keep participants safe and keep results reliable.

Randomization is the process of assigning people by chance to groups that receive different treatments in later-phase trials. A computer is most often used to assign people to groups. In the simplest design, one group receives the study treatment and another group receives standard treatment. Researchers then compare the groups.

Randomization helps prevent bias, which happens when a trial's results are affected by human choices or other factors not related to the treatment. If you are thinking about joining a trial that uses randomization, it is important to understand that neither you nor your doctor can choose which group you will be in.

Placebos are rarely used in cancer treatment clinical trials. In most cases, one group receives the new treatment and another receives the already approved standard treatment. If placebos are used, you will always be told ahead of time and can ask questions before deciding to join. Placebos are generally used when no standard treatment exists, and they may be used in other kinds of trials, such as prevention trials.