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    Understanding Clinical Trials

    What are Clinical Trials and Why are They Important?

    A clinical trial is an organized research study designed to investigate new methods of preventing, detecting, diagnosing, or treating an illness or disease, such as cancer. In some instances, clinical trials attempt to improve a patient’s quality of life. When studying cancer treatment, researchers generally attempt to determine whether a new method of treatment is superior to the standard (currently approved) treatment of the ailment.

    Clinical trials are extremely important in discovering new techniques to fight disease. For example, many of the advances in breast cancer detection and treatment resulted from clinical trials. These advances include:

    Despite the importance of clinical trials to both patients and researchers, a recent survey by the American Society of Clinical Oncology (ASCO) shows that only 2% to 3% of adult patients participate in clinical trials. Comparatively, 60% to 70% of children with cancer are enrolled in trials. Of the 6,000 cancer adult patients surveyed by the ASCO, 84% said they were unaware of trials or unsure they would qualify for participation in a trial. Other reasons for low participation include the concern about medical costs, fear that treatment would not be adequate, and the concern of traveling long distances for treatment.

    A current clinical trial is investigating whether the drug raloxifene (left) is as effective as tamoxifen (right) at preventing breast cancer in high-risk women. The STAR trial is still enrolling post-menopausal women in the U.S., Canada, and Puerto Rico. Click here to learn more about the STAR trial.

    How are Clinical Trials Planned, Approved and Conducted?

    Before a new type of examination or treatment is approved by the U.S. Food and Drug Administration (FDA) for general use in the United States, it must first be evaluated in clinical trials. Clinical trials are typically conducted at universities, cancer centers, hospitals, or clinics. Before a clinical trial may be conducted, the proposed trial must be reviewed by an Institutional Review Board (IRB). An IRB is a separate board of scientists, physicians, and nurses who are not associated with the clinical trial. Once approved by the board, the trial is closely monitored by the IRB and given a formal review each year (or other interval depending on the length of the trial). Click here to learn more about the U.S. drug approval process.

    Researchers for each clinical trial follow an accepted protocol—a planned course of action. For cancer treatment, the protocol includes dosage levels, frequency, and duration of treatment. Protocols also establish the frequency and type of laboratory work or other tests needed to assess a patient’s progress. Clinical trials for cancer treatment may have one, two, three, or four different treatment plans. Usually, participants in trials with more than one treatment plan are randomly selected to receive one of the plans. Many clinical trials are double blind; neither the patient nor the researcher knows what type of treatment is being administered to a given patient. Double blind studies allow researchers to clearly see what the true benefits and side effects of a drug or treatment may be without the influence of other factors.

    Before entering a clinical trial, the patient must give his or her informed consent. This means that the researchers must explain the protocol and goal of the clinical trial and inform the patient of possible benefits and risks of participation. A patient may then freely decide whether to participate in the trial. Clinical trials are not binding; patients may leave at any time.

    What are the Different Types ("Phases") of Clinical Trials?

    There are several different types of clinical trials:

    Phase I trials usually test a new type of cancer treatment and are only given to a small number of participants. The purpose of a Phase I trial is to learn how to administer a treatment safely. Researchers will closely monitor the participants’ side effects and adjust dosages if need be.

    Phase II trials attempt to determine patients’ responses to treatments. Typically 30 to 40 people participate in Phase II trials. In Phase II cancer treatment trials, participants are closely monitored to see if their cancerous tumors shrink during treatment. If a patient’s tumor shrink, it is responsive to treatment. If at least one-fifth of the participants "respond" to treatment, the treatment is considered successful. Researchers of Phase II trials also monitor side effects. If enough patients respond to therapy, the trial moves to Phase III.

    Phase III trials enroll a large number of participants (sometimes thousands). Patients are usually divided into groups: one group receives standard therapy (control group) and the other group receives the new therapy. For example, the STAR clinical trial (Study of Tamoxifen and Raloxifene) is a Phase III trial that is enrolling 22,000 post-menopausal women 35 years of age or older who are at increased risk for developing breast cancer. The STAR Trial will compare the long-term safety of using the drugs tamoxifen and raloxifene to prevent breast cancer. As with Phase I and Phase II trials, Phase III participants are closely monitored for potentially dangerous side effects. If side effects become too severe, the trial may be canceled.

    Category # of Participants Purpose
    Phase I Less than 10 tests how to administer a new therapy, exam, or preventive option
    Phase II 30-40 tests patient responses to a new therapy, exam, or preventive option
    Phase III 100-1000+ compares new therapy exam or preventive option to a standard one
    Phase IV varies For marketing purposes, to compare the effectiveness of two therapies already on the market or to study new uses of therapies
    Adjuvant varies For cancer patients, determines if additional therapy will reduce chances of recurrent cancer.

    Phase IV trials may be conducted for marketing purposes after a treatment has already been approved by the FDA. These trials vary in the number of participants and typically compare two treatments that are approved for similar uses to determine which one is more effective. For example, after the breast cancer drug tamoxifen was FDA approved to treat advanced breast cancer, researchers investigated whether it could also prevent breast cancer in women at high risk for the disease (tamoxifen was later FDA approved for this use too). Phase IV trials may also be conducted to study new uses or the cost effectiveness of FDA-approved treatments.

    Another type of clinical trial, an adjuvant trial, attempts to determine whether additional therapy will help eliminate the possibility of a recurrence of cancer in patients at high risk of recurrence after surgery. For example, chemotherapy is found to help prevent breast cancer recurrence in many women in conjunction with breast surgery. If an adjuvant therapy is found beneficial in the trial, it may become standard treatment.

    What are the Benefits and Risks of Participating in Clinical Trials?

    Depending on the type and purpose of the trial, the benefits and risks vary significantly. The following table summarizes possible benefits and risks that patients should carefully consider before enrolling in a clinical trial.

    Possible Benefits of Trials Possible Risks of Trials
    • having access to potentially more effective therapies than those currently available
    • receiving quality medical care from leading physicians
    • being closely monitored for possible negative effects
    • sometimes receiving treatment at a reduced rate or free of charge
    • helping to further new research that may result in significant medical advances
    • for patients in cancer therapy trials assigned to control groups, they still receive the top standard therapy available today
    • patients may not receive the therapy under investigation (may receive a placebo—inactive pill—instead)
    • the new therapy may not be more effective than the standard, thoroughly tested therapy
    • in Phase I trials, not knowing the safety consequences of the new therapy (risk is less in Phase III trials)
    • new therapy may have unexpected, possibly severe side effects or may be less effective than standard of care
    • insurance companies may not cover all costs of clinical trials

    What Should Patients Know Before Entering a Clinical Trial?

    Patients interested in participating in clinical trials should ask their physicians to thoroughly explain the trial, including its risks and benefits. Patients should learn:

    • The purpose of the trial
    • How many people will participate
    • What type of tests and treatments patients must undergo
    • How long the trial will last
    • The potential side effects of tests or treatments
    • What type of long-term follow-up care is provided
    • Whether patients will have to cover any costs of the trial. If so, whether the patient’s insurance cover the costs or if financial aid is available

    The following terms may be helpful to patients who are considering participating in clinical trials:

    Protocol The planned course of action for the clinical trial. The protocol is established prior to the start of the trial and states the number of participants, eligibility requirements, agents that will be used, dosages, duration, how data is collected, etc.
    Investigator A researcher in a clinical trial.
    Sponsor The party or parties responsible for funding the clinical trial.
    Institutional Review Board (IRB) An independent board of scientists, physicians, and nurses who review the clinical trial protocol to ensure patient safety.
    Informed consent A patient’s decision to participate in the clinical trial after being informed of the potential benefits and risks of participation. Participants may withdraw their consent at any time and leave the trial.
    Double blind Term used to describe a clinical trial in which neither the patient nor the researcher knows which agents are being administered to which patients. This helps prevent bias.
    Intervention group The group of participants receiving the new preventive or treatment agent that is being evaluated in the clinical trial.
    Control group The group of participants receiving a standard treatment or placebo (see below) that is being compared to the new agent in the clinical trial.
    Randomization Assigning participants by chance to either the intervention group or the control group. Randomization is often done with a computer.
    Placebo An inactive substance that may be given to participants in a clinical trial. Sometimes called a sugar pill.
    Follow-up Monitoring of participants for a specified time after the clinical trial is completed.
    Prospective study A study of a group of patients that is conducted as they are undergoing a treatment or preventive measure.
    Retrospective study A study of a group of patients after they have already undergone a treatment or preventive measure. "Recall bias," unintentional inaccurate reporting of certain information, can sometimes influence a retrospective study.

    Directory of Online Clinical Trial Listings

    Updated: June 28, 2007