A clinical trial is classified according to which of three basic questions it is designed to answer. These questions relate to the experimental treatment's mechanism of action and potential toxicity (phase I), its effectiveness in a small group of cancer patients with specific cancers (phase II), and its effectiveness compared to standard therapy or other available treatments in a large, more varied group of patients with specific cancer (phase III).
These research stages can take a long time before new treatments can be safely used in cancer patients. But where the goal is to provide the best treatments possible to as many people as possible, well-organized, careful studies are an absolute necessity.
Phase I Clinical Trials
The first step in a clinical trial is for doctors to determine whether a potential treatment is well tolerated. Whether or not the treatment is later proven effective, it must first be determined what dosages patients can take without causing harm.
These preliminary human tests, called phase I studies, may carry significant risks. Moreover, only a small minority of patients in phase I studies have any therapeutic response. For these reasons, participation in phase I studies is generally offered only to a small group of individuals who have exhausted the standard treatment options. The information gained about a potential treatment's effects in patients and any early findings on its effectiveness are critical for the design of later-phase studies.
Phase II Clinical Trials
After a potential treatment is found to be well tolerated in phase I trials, it moves to phase II trials, where doctors study the treatment's effectiveness, again in a small group of cancer patients, this time with a similar type of cancer. Doctors closely study the results of the first two phases to decide whether to stop testing the treatment or to proceed to a phase III trial.
Phase III Clinical Trials
If a potential treatment is found to be well tolerated at doses that are effective against disease, the next step is usually a phase III study. While monitoring potential side effects, phase III trials compare the experimental treatment's effectiveness against standard therapy for a particular type of cancer. Phase III trials involve a much larger group of patients, who are each assigned either to the new treatment or to the standard therapy in a prospective, randomized study.
Randomization
In order to study the relative effectiveness of potential treatments, investigators usually assign participants randomly to one of two groups. One group receives the standard, already accepted therapy, while the other group receives the experimental treatment. In this way, the effectiveness of the new drug can be assessed to see if it is better than what is already being offered. In phase III studies, doctors look for more than just tumor shrinkage. They also look for longer life, better quality of life, fewer side effects, and fewer cases of cancer returning.
Some potential clinical trial participants are concerned that they may be assigned to a group using a placebo, or inactive, drug. It is important to note that people will never receive a placebo in phase III trials if standard therapy exists -- patients would only potentially receive a placebo if there were no standard therapies to test against.
Clinical trials can be stopped at any point if researchers following the trial notice that one group is doing significantly better -- or worse -- than the other. For example, when the National Cancer Institute did the first tamoxifen prevention trial in women at an increased risk of breast cancer and noted that those who took tamoxifen developed significantly fewer cancers, they stopped the study early and informed all the participants that those who had been taking a placebo could switch to the active drug.
