Introduction to Clinical Studies

Choosing to participate in a clinical trial is an important personal decision. In addition, it is often helpful to talk to a physician, family members, or friends about deciding to join a trial. After identifying some trial options, the next step is to contact the study research staff and ask questions about specific trials. Before you do, however, take a few minutes to read the following basic information.

What is a clinical trial?

A clinical trial is a research study to answer specific questions about vaccines, new therapies or new ways of using known treatments. Clinical trials (also called medical research and research studies) are used to determine whether new drugs or treatments are both safe and effective. Carefully conducted clinical trials are the fastest and safest way to find treatments that work in people.

Before a pharmaceutical company can begin testing new treatments in humans, it conducts extensive tests with animals and human cells. Once a treatment is considered successful in pre-clinical and laboratory tests, the company files an Investigational New Drug application (IND) with the Food and Drug Administration (FDA) for permission to begin testing the treatment in humans.

What are the different types of clinical trials?

Treatment trials test new treatments, new combinations of drugs, or new approaches to surgery or radiation therapy.

Prevention trials look for better ways to prevent disease in people who have never had the disease or to prevent a disease from returning. These approaches may include medicines, vitamins, vaccines, minerals, or lifestyle changes.

Screening trials test the best way to detect certain diseases or health conditions.

Quality of Life trials (or Supportive Care trials) explore ways to improve comfort and the quality of life for individuals with a chronic illness.

What are the phases of clinical trials?

Clinical trials are conducted in phases. The trials at each phase have a different purpose and help scientists answer different questions:

In Phase I trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects. These initial studies, used to determine the metabolism and pharmacologic actions of drugs in humans, the side effects associated with increasing doses, and to gain early evidence of effectiveness, may include healthy participants and/or patients.

In Phase II trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety. These phase II controlled clinical studies are used to evaluate the effectiveness of the drug for a particular indication or indications in patients with the disease or condition under study and to determine the common short-term side effects and risks. Most of these studies are "randomized", which means that one group of people is given the experimental drug and another group (control group) is given a standard treatment or placebo. They may also be "blinded" trials in which neither the patients nor the doctor knows which drug is being given to whom. This helps to keep the results unbiased and more reliable.

In Phase III trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely. Both expanded controlled and uncontrolled trials are done after preliminary evidence suggesting effectiveness of the drug has been obtained, and are intended to gather additional information to evaluate the overall benefit-risk relationship of the drug and provide an adequate basis for physician labeling. Once a treatment is tested in a Phase III trial, the pharmaceutical company can apply to the FDA for clearance to market the drug.

In Phase IV trials, studies are done after the drug is on the market to gather additional information including the drug's risks, benefits, and optimal use. Often the drug is compared to others like it and studied for its long-term effects and impact on patients. Some phase IV trials are done to determine the cost-effectiveness of the new drug in relation to other treatments.

Why participate in a clinical trial?

Participants in clinical trials can play a more active role in their own health care, gain access to new research treatments before they are widely available, and help others by contributing to medical research.

Where do the ideas for trials come from?

Ideas for clinical trials usually come from researchers. After researchers test new therapies or procedures in the laboratory and in animal studies, the treatments with the most promising laboratory results are moved into clinical trials. During a trial, more and more information is gained about a new treatment, its risks and how well it may or may not work.

Who sponsors or pays for clinical trials?

Clinical trials are sponsored or funded by a variety of organizations or individuals such as physicians, medical institutions, foundations, voluntary groups, and pharmaceutical companies, in addition to federal agencies such as the National Institutes of Health (NIH), the Department of Defense (DOD), and the Department of Veteran's Affairs (VA.) Trials can take place in a variety of locations, such as hospitals, universities, doctors' offices, or community clinics. The sponsor hires the physicians to conduct the trial and often pays for the care given to the patients. Sometimes patients are also paid a small fee to participate.

What is a protocol?

A protocol is a study plan on which all clinical trials are based. The plan is carefully designed to safeguard the health of the participants as well as answer specific research questions. A protocol describes what types of people may participate in the trial; the schedule of tests, procedures, medications, and dosages; and the length of the study. While in a clinical trial, participants following a protocol are seen regularly by the research staff to monitor their health and to determine the safety and effectiveness of their treatment.

What is a placebo?

A placebo is an inactive pill, liquid, or powder that has no treatment value. In clinical trials, experimental treatments are often compared with placebos to assess the treatment's effectiveness. In some studies, the participants in the control group will receive a placebo instead of an active drug or treatment.

What is a control or control group?

A control is the standard by which experimental observations are evaluated. In many clinical trials, one group of patients will be given an experimental drug or treatment, while the control group is given either a standard treatment for the illness or a placebo.

What are the benefits and risks of participating in a clinical trial?

Benefits

Clinical trials that are well-designed and well-executed are the best treatment approach for eligible participants to:

• Play an active role in their own health care.
• Gain access to new research treatments before they are widely available.
• Obtain expert medical care at leading health care facilities during the trial.
• Help others by contributing to medical research.

Risks

There are risks to clinical trials.

• There may be unpleasant, serious or even life-threatening side effects to treatment.
• The treatment may not be effective for the participant.
• The protocol may require more of their time and attention than would a non-protocol treatment, including trips to the study site, more treatments, hospital stays or complex dosage requirements.

How is the safety of the participant protected?

The ethical and legal codes that govern medical practice also apply to clinical trials. In addition, most clinical research is federally regulated with built in safeguards to protect the participants. The trial follows a carefully controlled protocol, a study plan that details what researchers will do in the study. As a clinical trial progresses, researchers report their results at scientific meetings, to medical journals, and to various government agencies. Names of individual participants remain secret and are not mentioned in these reports.

Every clinical trial in the U.S. must be approved and monitored by an Institutional Review Board (IRB) to make sure the risks are as low as possible and are worth any potential benefits. An IRB is an independent committee of physicians, statisticians, community advocates, and others that ensures that a clinical trial is ethical and the rights of study participants are protected. Federal regulations insure that all institutions that conduct or support biomedical research involving people must have an IRB that initially approves and periodically reviews the research.

Can a participant leave a clinical trial after it has begun?

Yes. A participant can leave a clinical trial, at any time. When withdrawing from the trial, the participant should let the research team know about it, and the reasons for leaving the study.

What is informed consent?

Informed consent is the process of learning the key facts about a clinical trial before deciding whether or not to participate. It is also a continuing process throughout the study to provide information for participants. To help someone decide whether or not to participate, the doctors and nurses involved in the trial explain the details of the study. If the participant's native language is not English, translation assistance can be provided. Then the research team provides an informed consent document that includes details about the study, such as its purpose, duration, required procedures, and key contacts. Risks and potential benefits are also explained in the informed consent document. The participant then decides whether or not to sign the document. Informed consent is not a contract, and the participant may withdraw from the trial at any time.

What kind of preparation should a potential participant make for the meeting with the research coordinator or doctor?

• Plan ahead and write down possible questions to ask.
• Ask a friend or relative to come along for support and to hear the responses to the questions.
• Bring a tape recorder to record the discussion to replay later.

What should people consider before participating in a trial?

People should know as much as possible about the clinical trial and feel comfortable asking the members of the health care team questions about the care expected while in a trial and the cost of the trial. The following questions might be helpful for the participant to discuss with the health care team. Some of the answers to these questions are found in the informed consent document.

• What is the purpose of the study?
• Who is going to be in the study?
• Why do researchers believe the new treatment being tested may be effective? Has it been tested before?
• What kinds of tests and treatments are involved?
• How do the possible risks, side effects, and benefits in the study compare with my current treatment?
• How might this trial affect my daily life?
• How long will the trial last?
• Will hospitalization be required?
• Who will pay for the treatment?
• Will I be reimbursed for other expenses?
• What type of long-term follow up care is part of this study?
• How will I know that the treatment is working? Will results of the trials be provided to me?
• Who will be in charge of my care?

Does a participant continue to work with a primary health care provider while in a trial?

Yes. Most clinical trials provide short-term treatments related to a designated illness or condition, but do not provide extended or complete primary health care. In addition, by having the health care provider work with the research team, the participant can ensure that other medications or treatments will not conflict with the protocol.

What are side effects and adverse reactions?

Side effects are any undesired actions or effects of drug or treatment. Negative or adverse effects may include headache, nausea, hair loss, skin irritation, or other physical problems. Experimental treatments must be evaluated for both immediate and long-term side effects.

For More Information

The National Institutes of Health provides extensive information about clinical trials at their website: An Introduction to Clinical Trials.