What Happens in a Clinical Trial? What Are the Risks?

by Food and Drug Administration (FDA)

(Page 2 of 3)

What Happens in a Clinical Trial?

Every clinical trial is carefully designed to answer certain research questions. A trial plan called a "protocol" maps out what study procedures will be done, by whom, and why. Products are often tested to see how they compare to standard treatments or to no treatment. The FDA often provides extensive technical assistance to researchers conducting clinical trials, helping them design better trials that can characterize effects of a new product more efficiently, while reducing risks to those participating in the trials.

The clinical trial team includes doctors and nurses as well as other health care professionals. This team checks the health of the participant at the beginning of the trial and assesses whether that person is eligible to participate. Those found to be eligible — and who agree to participate — are given specific instructions, and then monitored and carefully assessed during the trial and after it is completed.

Done at hospitals and research centers around the country, clinical trials are conducted in phases. Phase 1 trials try to determine dosing, document how a drug is metabolized and excreted, and identify acute side effects. Usually, a small number of healthy volunteers (between 20 and 80) are used in Phase 1 trials.

Phase 2 trials include more participants (about 100-300) who have the disease or condition that the product potentially could treat. In Phase 2 trials, researchers seek to gather further safety data and preliminary evidence of the drug's beneficial effects (efficacy), and they develop and refine research methods for future trials with this drug. If the Phase 2 trials indicate that the drug may be effective — and the risks are considered acceptable, given the observed efficacy and the severity of the disease — the drug moves to Phase 3.

In Phase 3 trials, the drug is studied in a larger number of people with the disease (approximately 1,000-3,000). This phase further tests the product's effectiveness, monitors side effects, and, in some cases, compares the product's effects to a standard treatment, if one is already available. As more and more participants are tested over longer periods of time, the less common side effects are more likely to be revealed.

Sometimes, Phase 4 trials are conducted after a product is already approved and on the market to find out more about the treatment's long-term risks, benefits, and optimal use, or to test the product in different populations of people, such as children.

Phase 2 and Phase 3 clinical trials generally involve a "control" standard. In many studies, one group of volunteers will be given an experimental or "test" drug or treatment, while the control group is given either a standard treatment for the illness or an inactive pill, liquid or powder that has no treatment value (placebo). This control group provides a basis for comparison for assessing effects of the test treatment. In some studies, the control group will receive a placebo instead of an active drug or treatment. In other cases, it is considered unethical to use placebos, particularly if an effective treatment is available. Withholding treatment (even for a short time) would subject research participants to unreasonable risks.

The treatment each trial participant receives is often decided by a process called "randomization." This process can be compared to a coin toss that is done by computer. During clinical trials, no one likely knows which therapy is better, and randomization assures that treatment selection will be free of any preference a physician may have. Randomization increases the likelihood that the groups of people receiving the test drug or control are comparable at the start of the trial, enabling comparisons in health status between groups of patients who participated in the trial.

In conjunction with randomization, a feature known as "blinding" helps ensure that bias doesn't distort the conduct of a trial or the interpretation of its results. Single-blinding means the participant does not know whether he or she is receiving the experimental drug, an established treatment for that disease, or a placebo. In a single-blinded trial, the research team does know what the participant is receiving.

A double-blind trial means that neither the participant nor the research team knows during the trial which participants receive the experimental drug. The patient will usually find out what he or she received at a pre-specified time in the trial.

Meritt participated in an NIH study of a vaccine and chemotherapy combination in previously untreated mantle cell lymphoma. Following more than a year of medical treatment through the study, her cancer went into remission.

What Are the Risks?

Some treatments being studied can have unpleasant, or even serious, side effects. Often these are temporary and end when the treatment is stopped. Others, however, can be permanent. Some side effects appear during treatment, and others may not show up until after the study is over. The risks depend on the treatment being studied and the health of the people participating in the trial. All known risks must be fully explained by the researchers before the trial begins. If new risk information becomes available during the trial, participants must be informed.

"I didn't tolerate the drugs well," says Leslie Garelick of Olney, Md., referring to the two rounds of experimental chemotherapy she received as a participant in a clinical trial of a breast cancer treatment. Because her white blood cell counts were dangerously low, she was forced to skip some of the scheduled trial treatments. On the advice of her doctor, the 30-year-old mother of two withdrew from the trial and received standard treatment for breast cancer. Even though she quit the study, Garelick's experience gave the research team information about tolerance to the drug being tested.

About the Author

www.fda.gov
FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.