Clinical Trials

As you and your doctor consider your options for treatment, you may wish to consider participating in a clinical trial of some type. Clinical trials are research studies designed to find better ways to treat cancer and help cancer patients. Clinical trials test many types of treatment such as new drugs, new approaches to surgery or radiation therapy, new combinations of treatments or new methods such as gene therapy.

A clinical trial is one of the final stages of a long and careful cancer research process. The search for new treatments begins in the laboratory, where scientists first develop and test new ideas. If an approach seems promising, the next step may be testing a treatment in animals to see how it affects cancer in a living being and whether it has harmful effects. Of course, treatments that work well in the lab or in animals do not always work well in people. Studies are done with cancer patients to find out whether promising treatments are safe and effective.

Why Are Clinical Trials Important?
Clinical trials are important in two ways. First, cancer affects us all, whether we have it, care about someone who does, or worry about getting it in the future. Clinical trials contribute to knowledge and progress against cancer. If a new treatment proves effective in a study, it may become a new standard treatment that can help many patients. Many of today's most effective standard treatments are based on previous study results. Examples include treatments for breast, colon, rectal and childhood cancers. Clinical trials may also answer important scientific questions and suggest future research directions. Because of progress made through clinical trials, many people treated for cancer are now living longer.

Second, the patients who take part in a trial may be helped personally by the treatment(s) they receive. They get up-to-date care from cancer experts, and they receive either a new treatment being tested or the best available standard treatment for their cancer. Of course, there is no guarantee that a new treatment being tested or a standard treatment will produce good results. New treatments also may have unknown risks. But if a new treatment proves effective or more effective than standard treatment, study patients who receive it may be among the first to benefit. Some patients receive only standard treatment and benefit from it.

In the past, clinical trials were sometimes seen as a last resort for people who had no other treatment choices. Today, patients with common cancers often choose to receive their first treatment in a clinical trial.

What Happens in a Clinical Trial?
In a clinical trial, patients receive treatment and doctors carry out research on how the treatment affects the patients. While clinical trials have risks for the people who take part, each study also takes steps to protect patients.

When you take part in a clinical trial, you receive your treatment in a cancer center, hospital, clinic, and/or doctor's office. Doctors, nurses, social workers and other health professionals may be part of your treatment team. They will follow your progress closely. You may have more tests and doctor visits than you would if you were not taking part in a study. You will follow a treatment plan your doctor prescribes, and you may also have other responsibilities such as keeping a log or filling out forms about your health. Some studies continue to check on patients even after their treatment is over.

How Is the Research Carried Out? How Are Patients Protected?
In clinical trials, both research concerns and patient well-being are very important. To help protect patients and produce sound results, research with people is carried out according to strict scientific and ethical principles. These include:

Each clinical trial has a protocol (action plan) that explains how it will work. The study's investigator, usually a doctor, prepares the protocol for the study. This plan explains what will be done in the study and why. It outlines how many people will take part in the study, what medical tests they will receive and how often, and the treatment plan. The same protocol is used by each doctor who takes part in the trial.

For patient safety, each protocol must be approved by the organization that sponsors the study (such as the National Cancer Institute) and the institutional review board (IRB) at each hospital or other study site. This board, which includes consumers, clergy and health professionals, reviews the protocol to try to be sure that the research will not expose patients to extreme or unethical risks.
Each study enrolls people who are alike in key ways. The study's protocol describes the characteristics that all patients in the study must have. Called eligibility criteria, these guidelines differ from study to study, depending on the research purpose. They may include age, gender, the type and stage of cancer, and whether cancer patients who have had prior cancer treatment or who have other health problems can take part.

Using eligibility criteria is an important principle of medical research that helps produce reliable results. During a study, these criteria help protect patient safety, so that people who are likely to be harmed by study drugs or other treatments are not exposed to the risk. After results from the study are in, these criteria also help doctors know which patient groups will benefit if the new treatment being studied is proven to work. For instance, a new treatment may work for one type of cancer but not for another, or it may be more effective for men than women.

Cancer clinical trials include research at three different phases. Each phase answers different questions about the new treatment:

Phase I trials are the first step in testing a new treatment in humans. In these studies, researchers look for the best way to give a new treatment (e.g., by mouth, IV drip, or injection? how many times a day?). They also try to find out if and how the treatment can be given safely (e.g., best dose?); and they watch for any harmful side effects. Because less is known about the possible risks and benefits in Phase I, these studies usually include only a limited number of patients who would not be helped by other known treatments.

Phase II trials focus on learning whether the new treatment has an anticancer effect (e.g., Does it shrink a tumor? improve blood test results?). As in Phase I, only a small number of people take part because of the risks and unknowns involved.

Phase III trials compare the results of people taking the new treatment with results of people taking standard treatment to determine which group has better survival rates and fewer side effects. In most cases, studies move into Phase III testing only after a treatment shows promise in Phases I and II. Phase III trials may include hundreds of people around the country.
In Phase III trials, people are assigned at random to a group to receive either the new treatment (the treatment group) or the standard treatment (the control group). This method, called randomization, helps avoid having the study's results affected by human choices or other factors not related to the treatments being tested.

In some studies, researchers do not tell the patient whether he or she is in the treatment or control group (called a single blind study). This approach is another way to avoid bias, because when people know what drug they are taking, it might change the way they react. For instance, patients who knew they were taking the new treatment might expect it to work better and report hopeful signs because they want to believe they are getting well. This could bias the study by making results look better than they really are. Some studies are done as double blind studies, in which neither the doctor nor the patient knows until the study is over to which group each patient belongs. This is done to avoid bias on the part of the observing doctor as well as the patient.

Why Do Phase III Clinical Trials Compare Treatment Groups?
Comparing similar groups of people taking different treatments for the same type of cancer is another way to make sure that study results are real and caused by the treatment rather than by chance or other factors. Comparing treatments with each other often shows clearly which one is more effective or has fewer side effects.

Another reason Phase III trials compare the new treatment with standard treatment is so that no one in a study is left without any treatment when standard treatment is available, which would be unethical. When no standard treatment exists for a cancer, some studies compare a new treatment with a placebo (a look-alike pill that contains no active drug). However, you will be told if this is a possibility before you decide whether to take part in a study.

Paying for Clinical Trials
As you consider enrolling in a clinical trial, you will face the critical issue of how to cover the costs of care. Even if you have health insurance, your coverage may not include some or all of the patient care costs associated with a clinical trial. This is because some health plans define clinical trials as "experimental" or "investigational" procedures. In 2000, Medicare began covering beneficiaries' patient care costs in clinical trials. Up-to-date information about what Medicare will cover can be found by writing: Clinical Trial Policy, Office of Clinical Standards and Quality, Health Care Financing Administration, 7500 Security Boulevard, S3-02-01, Baltimore, MD 21244 or on the Web site of the Centers for Medicare & Medicaid (formerly the Health Care Financing Administration) at http://www.hcfa.gov/coverage/8d.htm.

Your Doctor Can Tell You More
If you have any questions about how clinical trials work, ask your doctor, nurse or other health professional.