Clinical trials

(medicine) A research study used to find better ways to treat individuals with a specific disease, patients are evaluated after being administered a new treatment or drug.

Definition

A clinical trial is a carefully designed research study that is carried out with human volunteers. The trial is designed to answer specific questions concerning the effectiveness of a drug, treatment, or diagnostic method, or to improve patients' quality of life.

Description

Qualification for a clinical trial involves the selection of various desirable criteria (inclusion criteria), as well as criteria by which volunteers are rejected (exclusion criteria). Typical criteria include age, gender, the type and severity of the disease, prior treatment, and other medical conditions.

Depending on the clinical trial, the volunteers that are recruited could be healthy or ill with the disease under study. There are a number of different types of clinical trials that utilize differing types of study plans (protocols). A treatment trial evaluates a new treatment, new drug combinations, new surgical strategies, or innovative radiation therapy. A prevention trial seeks to find better ways to prevent disease from occurring or prevent disease from returning. Medicines, vaccines, vitamins, and lifestyle changes can all be candidates for a prevention trial. A diagnostic trial is designed to find better means of diagnosis for a particular disease or medical condition. A screening trial is designed to determine the best way to detect a particular disease or medical condition. Finally, a quality of life trial (supportive care trial) seeks to improve the comfort and daily life of people with a chronic illness.

Clinical trials, particularly treatment and prevention trials, often have several components, or phases. The following phases (I-IV) relate to the scope of the trial:

• Phase I trial evaluates the new drug or treatment in a small group of people (less than 100). Humans do not necessarily need to participate in such a trial. Experiments in the lab using microbiological cultures or tissue cells may suffice. The trial's purpose is to provide early indications of a drug or treatment's safety, safe dosage range, and reveal any side effects.
• Phase II trial follows a phase I trial. A promising drug or treatment is tested on a larger group of people (100–300) to better determine the effectiveness and to monitor safety more critically. Use of a larger population can help reveal side effects that could be hidden by the use of only a few volunteers.
• Phase III trial evaluates a drug or treatment that has proven effective in the phase I and II trials and is tested on a large population (1,000–3,000) to confirm its effectiveness, reveal any rarer side effects, and gather information that will allow the drug or treatment to be safely marketed.
• Phase IV trial occurs after a product has been released in the marketplace. Monitoring of a drug or treatment in very large numbers of people provides further information on benefits and risks.

A typical clinical trial involves medical doctors and nurses, although social workers and other health care workers may also contribute. The members of the clinical team monitor the health of each volunteer at the outset and during the trial, give instructions, and often provide follow-up after the trial is completed. For a clinical trial volunteer, this means more visits to the health care facility than would normally occur, although compensation such as transportation expense is sometimes provided.

A critical part of a clinical trial is obtaining the consent of volunteers for their participation. It is mandatory that a trial's risks (i.e., side effects, little or no effect of treatment) and benefits (i.e., more proactive role in health care, access to new therapies, advance medical care) be clearly explained to participants. Once this is done, volunteers provide their informed consent by signing a document. This document is not legally binding, so volunteers are not obligated to complete the trial. An ethical clinical trial will never reveal the identities of the volunteers.

In addition to the drug being studied, clinical trials of new drugs will typically use a pill, liquid, or powder that looks the same as the active compound, but that has no medicinal value. This inactive compound, known as a placebo, is usually given to the control group of volunteers, who are compared to the test group that receives the active drug. Usually the volunteers do not know whether they receive a placebo or the active drug. A clinical trial can be designed so that the researchers are also unaware of which people receive the active drug. When volunteers and researchers are both unaware, the trial is described as being double blind. Volunteers are often assigned to the control or test groups at random. This action is designed to minimize any bias due to age, gender, race, or other factors.

Resources

OTHER

"An Introduction to Clinical Trials." ClinicalTrials.gov. January 21, 2004 (March 30, 2004). http://www.clinicaltrials.gov/ct/info/whatis.

ORGANIZATIONS

National Institutes of Health, Clinical Center. 6100 Executive Blvd., Suite 3C01MSC 7511, Bethesda, MD 20892-7511. (301) 496-2563 or (800) 411-1222; Fax: (301) 402-2984. occc@cc.nih.gov. http://www.cc.nih.gov/home.cgi.

Brian Douglas Hoyle, PhD

Key Terms: Leukemia, Maximum tolerated dose, Oncology, Osteosarcoma, Placebo, Protocol.

Definition

A clinical trial is a research study designed to answer specific medical questions regarding cancer care.

Description

The clinical trial is a scientific study that follows a written guideline (protocol) or recipe for treatment. It is the only scientific mechanism designed to test the effectiveness of new and promising therapies. The clinical trial provides intensive testing of new or updated treatment regimens. Almost all standard treatments in the field of oncology (cancer) originated from clinical trials. These trials are conducted by medical, surgical and radiation oncologists (cancer specialists).

Cancer clinical trials are the key to preventing, diagnosing and treating all types of cancer. It is estimated that 60% of all cancer patients in the United States are being cured. Yet, fewer than 3% of adult cancer patients participate in clinical trials. In contrast, about 71% of children enter clinical trials. This has led to major advancements in treatment and high cure rates for many childhood cancers such as Wilms' tumor (malignant neoplasm of the kidney), osteosarcoma (tumor of the bone), and childhood leukemia (cancer of the blood).

Types of Clinical Trials

Clinical trials that involve new drugs or devices for humans must first be tested in animals. When a new or investigational drug has been discovered that shows anti-tumor activity in laboratory animals, it is tested on a small number of patients with different types of cancer, usually in a university setting. These are called Phase I trials and are designed to test the maximum tolerated dose (MTD) and side effects or toxicities of a new drug. This phase also helps determine how a new drug should be given (by mouth or by injection). The patients being tested are those with advanced cancer who have exhausted other treatment options. These patients may not personally benefit from participation in the trial.

If the investigational agent or drug continues to show anti-tumor activity and if the side effects are tolerable and not life-threatening, the drug is moved into a Phase II trial for further testing. In a Phase II trial, the drug is offered to a specific group of patients having the same tumor type. The drug is being tested to determine if it regresses tumor growth. Additional information on side effects of the treatment is also evaluated in this phase.

If the drug continues to show response to the patient's cancer, it is moved into a Phase III trial. At this phase, the investigational treatment is compared to the standard cancer therapy. This is to ensure that no one in a study is left without any treatment when standard treatment is available. If there is no standard therapy, a placebo (a pill that looks like the drug being studied but contains no active medication) may be used for comparison. However, researchers must inform potential patients of this possibility before patients decide whether to participate. Patients are usually assigned their treatment by a process called randomization, which is similar to the toss of a coin. Comparison or randomized trials help researchers find the most effective treatment for a specific type of cancer.

The objectives of Phase III trials include tumor response to treatment, survival, and quality of life during therapy. This phase can involve 400-1000 patients. Anti-tumor response by a significant proportion of the involved patients indicates that the investigational drug or treatment is ready to be submitted to the Food and Drug Administration (FDA) for approval. If approved, the drug is released from investigational status and made available for commercial use in patients with the specifically tested type of cancer.

What to Expect As Part of a Clinical Trial

Taking part in a clinical trial does not mean that patients are seen as or treated like "guinea pigs," or that they will receive substandard care. Cancer patients who enroll in clinical trials may be the first to receive a new technique or drug that becomes the standard of care. Clinical trials, however, have risks, as well. The treatment or drug being tested is new, and the side effects may be unknown. The cancer patient, his or her loved ones, and the patient's physician must weigh the risks and benefits when deciding whether or not to enroll in a clinical trial.

When patients participate in a clinical trial, they receive treatment in a cancer center, hospital, clinic, and/or doctor's office. Doctors, nurses, social workers, and other health professionals may be part of the treatment team, and will closely monitor progress. Cancer clinical trial patients:

• are, as stated above, under close scrutiny
• are seen frequently by the members of the treatment team
• are tested often
• follow the treatment plan their doctor prescribes and as according to the study's protocol
• and may also have other responsibilities, such as keeping a log or filling out health forms. Some studies continue to check on patients after their treatment is completed.

Questions to Ask the Doctor

• Am I eligible for a clinical trial?
• Where can I get more information?

Resources

Books

Klimaszewski, Angela D., Jennifer L. Aikin, Monica A. Bacon, Susan A. DiStasio, Heidi E. Ehrenberger, and Bertie A. Ford, editors. Manual for Clinical Trials Nursing. Pittsburgh: Oncology Nursing Press, Inc., 2000.

Other

National Cancer Institute. Cancer Trials. [cited July 8, 2001]. .

National Cancer Institute. An Introduction to Clinical Trials. January 2000 National Cancer Institute. [cited July 8, 2001]. .

—Phyllis M. Stein, B.S., CCRP

Tests performed on human subjects.