Phase III clinical trials: Is it better than what’s already available?

Treatments that have been shown to work in phase II studies usually must succeed in one more stage of testing before they are approved for general use. Phase III clinical trials compare the safety and effectiveness of the new treatment against the current standard treatment.

Most phase III clinical trials have a large number of patients, at least several hundred. These studies are often done in many places across the country (or even around the world) at the same time. They are more likely to be offered by community-based oncologists.

Because doctors do not yet know which treatment is better, patients who volunteer for the study are often picked at random, (called randomized) to get either the standard treatment or the new treatment. When possible, neither the doctor nor the patient knows which of the treatments the patient is getting. This type of study is called a double-blind study. Randomization and blinding are discussed in more detail later on.

As with other studies, patients in phase III clinical trials are watched closely for side effects, and treatment is stopped if they are too bad. Placebos may be used in some phase III studies, but they are never used alone if there’s already a treatment available that works.

An example of a phase III clinical trial that could involve a placebo:

Li has just been diagnosed with cancer. His surgeon was able to remove the tumor, but tells Li that this kind of cancer returns in about one-third of patients. For this reason, doctors usually recommend giving a short course of chemotherapy drug D. Although this is the best drug available for reducing the chance the cancer will come back, some cancers still return after drug D is used.

Li’s doctor tells him that a new type of treatment, called “EX-3,” is now being studied. EX-3 was designed to be given along with drug D. Earlier studies in animals and people have shown that the combination of drug D and EX-3 seems to be safe and effective. But it’s not yet known if this combination will be better than the current standard of drug D alone in reducing the risk of the cancer coming back. So the doctors are testing it in a phase III clinical trial.

To do this, they’ve designed a study that assigns people with this cancer to 1 of 2 groups: one group will get drug D plus EX-3, while the other group will get drug D plus a placebo. The patients will not know whether they are getting EX-3 or the placebo. But all patients will be getting drug D, which is the accepted standard of care. The people who get EX-3 may do better than those who get the placebo. On the other hand, they may do worse because of side effects and other problems. Or both groups may do about the same, in which case EX-3 would not be any better than the placebo. (If this happens, drug D alone would remain the standard care.)

Li, in deciding whether to take part in the clinical trial, needs to understand that he will be randomly assigned to 1 of the 2 treatment groups, and neither he nor his doctor will have control over this. He also needs to understand that while on this study, he will not know if his group is getting EX-3 or a placebo (he may find out after the study ends).