Trial Phases

A clinical trial is only done after a preclinical trial on cell lines or mouse models are completed and there is good reason to believe that a new drug may improve the care of patients.

Clinical trials assess the features of a drug. For example, the research goal may be to learn if the drug is harmful to living tissue. Another goal may be to learn more about the chemical makeup of a drug. Clinical trials assess if drugs are safe for and work in people. Clinical trials have five phases.

Phase 0

Phase 0 trials are the first clinical trials done among people. Even though phase 0 studies are done in humans, this type of study isn’t like the other phases of a clinical trial. The purpose of this phase is to speed up and streamline the drug approval process.

The goal is learning how a drug is processed by the body and affects the body. In these trials, a very small dose of a drug is given to about 10 to 15 people. The researchers might test how the drug reaches the tumor, how the drug reacts in the human body, and how cancer cells in the human body react to the drug. Patients in these studies may need extra biopsies, scans and blood samples as part of the study process.

The biggest difference between phase 0 and the later stages of a clinical trial is that there is almost no chance the volunteer will benefit from taking part in a phase 0 trial – the benefit will be for other people in the future. Because drug doses are low, there is also less risk to the patient compared to phase 1 studies.

Phase I

Phase I trials aim to find the best dose of a new drug with the fewest side effects. The drug will be tested in a small group of 15 to 30 patients. Doctors start by giving very low doses of the drug to a few patients. Higher doses are given to other patients until side effects become too severe or the desired effect is seen. The drug may help patients, but Phase I trials are to test a drug’s safety. If a drug is found to be safe enough, it can be tested in a phase II clinical trial.

Overall, phase 1 trials are the ones with the most potential risks.

Phase II

Phase II trials further assess safety as well as drug efficacy. The drug is often tested among patients with a specific type of cancer. Phase II trials are done in groups of 25 to 100 patients. The types of benefit or response the doctors look for depends on the goal of the treatment. It might mean the cancer shrinks or disappears, or it might mean an extended period of time when the cancer doesn’t get any bigger, or there is a long time before the cancer comes back. In some studies, the benefit may be improved quality of life. Many studies look to see if people getting the new treatment live longer than they would have expected to without the treatment.

Often, new combinations of drugs are tested. Patients are closely watched to see if the drug works. However, the new drug is rarely compared to the current (standard-of-care) drug that is used, that is done in phase III. If a drug is found to work, it can be tested in a phase III clinical trial.

A key point is in phase II clinical trials no placebo is used.

Phase III

Phase III trials compare a new drug to the standard-of-care drug. These trials assess the side effects of each drug and which drug works better. Phase III trials enroll more than 100 patients.

Often, these trials are randomized. This means that patients are put into a treatment group, called trial arms, by chance. Randomization is needed to make sure that the people in all trial arms are alike. This lets scientists know that the results of the clinical trial are due to the treatment and not differences between the groups. A computer program is often used to randomly assign people to the trial arms. If you are randomized to an arm you are unhappy with, you are not obligated to go forward with the trial.

There can be more than two treatment groups in phase III trials, and a placebo can be sometimes used. The control group gets the standard-of-care treatment. The other groups get a new treatment. Neither you nor your doctor can choose your group. You may also not know which group you’re in until the trial is over.

Every patient in a phase III study is watched closely. The study will be stopped early if the side effects of the new drug are too severe or if one group has much better results. Phase III clinical trials are often needed before the FDA will approve the use of a new drug for the general public.

Phase IV

Phase IV trials test new drugs approved by the FDA. The drug is tested in several hundreds or thousands of patients. This allows for better research on short-lived and long-lasting side effects and safety. For instance, some rare side effects may only be found in large groups of people. Doctors can also learn more about how well the drug works and if it’s helpful when used with other treatments.