Clinical trial is a scientific study in which researchers evaluate a new method for diagnosing, treating, or preventing illness using patients or healthy volunteers. The researchers conducting clinical trials are often physicians. Such trials are among the most important tools for developing safe, effective new therapies.
Clinical trials are one step in a lengthy process. This process often starts with a basic observation in a scientific laboratory. The clinical study that results in a new drug or treatment may follow 8 to 10 years after the initial discovery. Sponsors of clinical trials include government agencies, major medical centers, and pharmaceutical and medical equipment companies. Because clinical trials involve living people, they must be designed and carried out according to strict scientific and ethical standards. Properly designed studies can be conducted on many treatments, including diets, drugs, medical devices, radiation, surgery, and vaccines or a combination of such methods.
Steps in a clinical trial.
Proper clinical trials are conducted in three parts called phases. In Phase I, a group of patients or other volunteers, called a cohort, is exposed to the drug or treatment to be evaluated. The purpose of this step is to determine if the drug or treatment is safe for human beings. Researchers will also try to determine the dose or amount of treatment that is effective. Phase I clinical trials are carried out with strict regulations and with the informed permission of the cohort or their families.
Once a treatment has been shown to be safe and the effective amount determined, a second phase of testing begins. In Phase II, a larger cohort is exposed to the treatment being tested to determine the best dosage or amount of treatment and how often treatment should be administered. Researchers also continue to evaluate the effectiveness of the drug or treatment in this phase of testing.
If a drug or product is found to be safe and at least somewhat effective, Phase III testing begins. Phase III studies are often comparative studies—that is, they compare the new treatment with one that is already accepted for the same illness. The purpose of this phase is to compare the safety and effectiveness of the treatments.
In the United States, if a drug or product proves safer or more effective than the existing treatment, the company that sponsored the trial can apply for approval from the U.S. Food and Drug Administration (FDA). The FDA is an agency in the Department of Health and Human Services that oversees the review and approval of new medicines and medical devices. Sometimes the product can be approved for marketing, but the FDA will require additional studies. Such studies may be required because only a limited number of patients were exposed to the new treatment in Phase III trials and more information is needed. Studies that continue to evaluate the safety of an approved product are called Phase IV or post-marketing clinical studies. Other countries and groups of countries have their own agencies and standards for approving new treatments.
Scientific principles in clinical trials.
Many clinical trials compare the results of medical care in two groups of patients. One group—called the treatment group—receives the new therapy that is being tested. The other group—called the control group—does not receive the new therapy. The control group may receive several alternative types of care, depending on the disease or condition being studied. In some cases, the treatment under investigation is simply omitted from the care of the control group. In other cases, patients in the control group are given a placebo << pluh SEE boh >> . A placebo is a “dummy treatment” that appears similar to the active treatment but lacks a key element, such as the effective ingredient in a pill. In still other situations, control groups may receive an established treatment that is already known to be effective.
In many trials, the treatment group and the control group receive care at the same time. Other trials compare a treatment group with a control group that received a different type of care in the past. This type of control group is called a historical control.
Researchers choose trial participants carefully to ensure that each group differs only with respect to the treatment being tested. All patients enrolled have the illness being studied at about the same stage of advancement. Aside from that illness, patients should be in the same general health and share other characteristics. Each group should have a similar mix of ages. Carefully matching groups reduces the possibility that some factor other than the treatment being studied caused any differences in outcome. The control group and treatment group must also be large enough to ensure that different outcomes did not happen simply by chance. In general, the larger a trial, the more confidence researchers place in its results.
Researchers also take steps to ensure that the procedure for assigning patients to each group does not affect the results of the trial. Many trials are conducted by researchers who are extremely hopeful that the treatment they are testing will work. Developing new treatments gives physicians and scientists the satisfaction of helping patients and may also bring career advancement or other honors. For these reasons, eager researchers might unintentionally put patients who seem most likely to be helped in the treatment group. The most common strategy for avoiding this problem is called randomization. In randomization, researchers do not choose how their patients are assigned. Instead, each patient’s placement in the control group or treatment group is determined by chance.
A further strategy for ensuring that the hopes of patients and researchers do not influence results is called blinding. Blinding conceals which group patients have been assigned to until the clinical trial is over. In a single blind study, patients do not know whether they have been assigned to the treatment group or the control group. In a double blind study, neither patients nor researchers know which group was which until after the conclusion of the trial. There are also triple blinded studies, in which the pharmacy or nurse is also unaware of which medicine—the new one or the placebo—is being given to an individual patient.
Members of both the treatment group and the control group are examined, tested, and observed closely for as long as a clinical trial lasts. In many cases, representatives of the sponsoring organization periodically check the records maintained by researchers in a trial. If an experimental treatment shows unexpectedly good results, researchers may stop the trial and make the new treatment available to all participants. Trials in which the treatment proves unexpectedly dangerous are also stopped. However, few studies produce such dramatic results, and most trials run their full course.
When the trial is finished, scientists collect data about all the patients and analyze the information with sophisticated methods of statistical analysis. The analysis determines whether any patients were helped and how great a benefit they experienced. Analysis of the data also reveals the frequency and severity of any side effects.
Participating in a clinical trial.
Patients who are interested in participating in a clinical trial should discuss the possibility with their doctors. Some government agencies and research centers provide lists on the Internet of the clinical trials that they sponsor. Trials are especially common for serious diseases in which the standard treatment offers little hope of a cure, such as AIDS and advanced cancer. If a patient is accepted for participation, researchers carefully explain the purpose of a trial, its potential benefit, and any expected risks or side effects. Receiving this explanation enables patients to give informed consent to enrolling. Informed consent means that participants fully understand and accept the known risks and possible benefits of a trial.
