Clinical research is performed in distinct segments called phases. Each phase of a clinical trial is designed to provide different information about the new treatment, such as the dose, safety, and efficacy (how well it works). The phases are described as I, II, and III.

Preclinical research

Before a new therapy can be given to patients, the underlying research hypothesis (the explanation for how the new therapy works) must be proven under controlled, artificial circumstances in a laboratory environment. This stage is called preclinical research, and it can take years to turn this knowledge into a new therapy.

If preclinical research proves successful, the sponsor of the trial files an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) requesting permission to begin trials in humans. If the IND application is approved, researchers can begin to investigate the new therapy, which includes an array of studies to determine whether there is enough evidence to support advancement to the next phase of investigation.

Phase I clinical trials

The goal of a phase I clinical trial is to prove that a new drug or treatment, which has proven to be safe for use in animals, also may be given safely to humans. Doctors collect data on the dose, timing, and safety of the investigational therapy. People who participate in phase I clinical trials are often the first to receive a new therapy or a new combination of therapies.

In phase I clinical trials, the dose of an investigational drug is gradually increased to determine the optimal safe dose. This process is called dose escalation. The first participants are given a small dose of the drug. If there are no or few side effects, the next group is given higher amounts of the drug until the doctors determine the optimal dose with the fewest side effects. The doctors also learn the best way to administer the new treatment, such as by mouth or through a vein. Finally, the doctors collect data on how the drug is absorbed, processed, and spread through the body.

Phase I clinical trials generally last several months to a year and involve a very small number of people, usually no more than 10 to 20. People whose cancers have not responded to prior chemotherapy are often offered participation in phase I clinical trials. However, phase I clinical trials do not test how well a drug works. Sometimes, a person's cancer will respond to investigational drugs in this phase, but this situation is rare.

Phase II clinical trials

Phase II clinical trials are designed to provide more detailed information about the safety of the treatment, as well as to evaluate the efficacy of the drug. These trials focus on determining whether the new treatment has an anticancer effect in a specific cancer such as shrinking a tumor or improving blood test results. Phase II clinical trials take about two years to complete and usually involve about 20 to 40 people. The response rate in this phase needs to be equal to or higher than the standard treatment in order to proceed to phase III clinical trials.

Phase III clinical trials

The goal of phase III clinical trials is to take a new treatment that has shown promising results when used to treat a small number of patients with a particular disease and compare it with the current standard of care for that specific disease. In this phase, data are gathered from large numbers of patients to determine whether the new treatment is more effective and possibly less toxic than the current standard treatment. Phase III clinical trials are usually randomized, meaning that patients are assigned treatment groups in a non-ordered way. Although phase III trials focus on patients with a specific disease, they typically include patients of various ages, multiple ethnicities, and both genders so that the results, once obtained, may be applicable to a large number of people. The number of people enrolled in a phase III clinical trial can range in the hundreds to thousands and take many years to complete.

Once a drug has been proven successful in a phase III clinical trial, the researchers can submit an application for FDA approval. If data from the clinical trials meet the FDA's standards, the treatment will be approved for a specified use. However, physicians sometimes prescribe a drug for a use not specified by the FDA, but rather based on studies published in peer-reviewed journals demonstrating effectiveness in treating other diseases, conditions, or symptoms; this is referred to as "off-label" use.