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Clinical research, also known as clinical trials, is a necessary part of every field of medicine. Clinical trials have contributed an enormous amount of data and considerable knowledge to cancer treatment. Although cancer research originates in a laboratory that is filled with test tubes and laboratory animals, human volunteers are the key to determining the absolute clinical benefit of new cancer treatments and techniques.
PHASE I, II, AND III TRIALS
Clinical trials for cancer are designed by experts with knowledge of specific types of cancer. Once the trial has been designed, it undergoes scrutiny by a scientific review committee, which typically resides at the institution of the trial’s origin. It is then submitted to a patient advocate-oriented institutional review board made up of both laypersons and professionals, who decide whether the trial as designed will inform the patient completely about all the possible consequences and benefits of the trial, as well as about existing alternative treatments. This information is put together into what is called an informed consent document, which participants must sign to indicate that they have been fully informed about the trial and their risks and responsibilities.
Clinical trials are then designated as being one of three types: Phase I, Phase II, or Phase III. The type of trial is determined by the trial’s design. A Phase I clinical trial involves testing new treatments or medicines for the sole purpose of determining whether patients can tolerate the medication. In other words, the prime concern is determining degree of toxicity. Because this is the initial trial, patients are not expected to improve while receiving the medication, but improvements can occur. This form of cancer research will often consist of a series of dose escalations to find what is known as the maximum tolerated dose, or MTD. The MTD is the highest dose of the studied therapy that can be tolerated by the subjects.1
After a Phase I study has determined that a medication or treatment is safe enough to be used by patients, a Phase II study then determines whether the treatment or medication is effective.2 In some situations, a trial can be both Phase I and Phase II at the same time. Phase II trials often consist of a few dozen patients.
There has been some recent interest among cancer researchers in what is known as a randomized Phase II approach. In this approach, the study subjects are divided into two groups: the experimental group and the control group. This type of trial has been controversial because it gives the impression that enough subjects are being studied for a comparison of treatment effectiveness to be made, when the numbers being studied are in fact not large enough to make any statistical statement of validity. A randomized Phase II study is often done to see if pursuing a more meaningful Phase III trial design would be worth the expense.
Phase III trials are a continuation of Phase II trials in that once a medication has shown evidence of effectiveness, it is often compared to what is considered the standard treatment or treatments to determine whether the new medication is an improvement. In Phase III trials, all patients receive a standard treatment for their particular cancer if a standard treatment exists. In some cases, this standard treatment may be what is known as best supportive care. All patients are randomized into two (or more) groups, which are commonly referred to as arms of the study. In many situations, one arm will receive the standard treatment and/or the new treatment being tested. This group may also be called the active group. The other arm—often referred to as the control group—will receive the standard treatment and/or a placebo. Neither the clinician nor the patient knows who is in which arm of the study.
After a Phase III trial has concluded and the data have been analyzed, medications or treatments go before the FDA for consideration of approval for treatment of the particular disorder for which the trial was designed. Sometimes this approval can be based on Phase II data if the benefits of the new treatment are obvious.