Background

• What are clinical research trials?
• Why do people participate in clinical research trials?

Clinical Research Trial Phases

• What are the different phases of clinical research trials?
• How are clinical research trials conducted?
• Who pays for the study treatment in a clinical research trial?

Safety

• How are people in clinical research trials protected?
• Are there risks in clinical research trials?

Pre-enrollment Information

• What questions should be asked about a clinical research trial?
• What is "informed consent"?
• What are eligibility criteria (inclusion and exclusion criteria)?
• Can clinical research trial participants leave a trial?

Drugs and Placebo

• Do all clinical research studies involve a placebo?
• What is a blinded or masked research trial?
• Why are patients "randomized" in some clinical research trials?

Your Doctor and the Clinical Research Trial

• Is a referral from my physician required for participation in a clinical research trial?
• Can clinical research trial participants still see their regular doctor?
• What happens to the research trial information?

What are clinical research trials? (top)
Before the U.S. Food and Drug Administration (FDA), can consider an investigational drug or treatment for approval, it must be show to be both safe and effective. Typically, this is accomplished via clinical research trials – carefully designed and monitored studies intended to test and evaluate investigational drugs and treatment plans.

Why do people participate in clinical research trials? (top)
People may be interested in clinical research trials for a variety of reasons. Some people participate in clinical research trials as a way to contribute to medical science and to help doctors and researchers find better ways to help others. Others participate in clinical research trials to receive investigational treatments because their illness is not responding to standard treatment. Their hope is that the study treatment - possibly an investigational drug or an investigational combination of drugs - will work better for them than standard therapy. This will not always be the case, because some investigational treatment strategies may not work as well as standard therapies or may have unexpected side effects. For this reason, everyone in a clinical research trial is carefully monitored. Frequent study-related medical exams and tests are performed to help ensure safety.

What are the different phases of clinical research trials? (top)
Clinical research trials are traditionally divided into different phases. Each phase is designed to gather specific information about the study drug or treatment.

Phase I: The first human tests of investigational drugs or therapies occur in Phase I trials. Phase I research trials are designed to determine the best dose of the study drug and to check for any potential side effects. These trials usually involve small numbers of participants. Because Phase I trials use study drugs that have never been tested in humans, they may involve significant risks.

Phase II: If an investigational drug is initially shown to be safe and well tolerated, it moves on to Phase II trials. These trials are designed to see how well the study drug works, usually in a larger group of participants.

Phase III: If the investigational drug is effective in Phase II trials, it may move on to Phase III trials. Phase III trials test the safety and how well the drug works in hundreds or even many thousands of participants. Often Phase III trials compare the study drug to an existing standard treatment in a randomized fashion.

Phase IV: These trials are conducted after the FDA has approved a drug and after the drug is on the market. Phase IV trials typically involve a large number of participants. They may evaluate new uses of existing therapies or be used to detect side effects that did not appear during Phase III studies.

How are clinical research trials conducted? (top)
The doctors and researchers running a clinical research trial develop a written plan detailing exactly how the trial will be conducted. This plan is called a protocol. It explains how the trial will be run, what information will be gathered, and what researchers hope to learn. It describes the blood tests, x-rays, and other tests that are used to assess how well each participant responds.

Who pays for the study treatment in a clinical research trial? (top)
For the most part, the study drugs used in clinical research trials are provided at no cost to the study participants. However, there may be other costs associated with the trial, which should be discussed prior to enrollment. Sometimes blood work, x-rays, and travel expenses may be provided at no charge and sometimes health insurance may cover the cost of some of these items. For instance, Medicare now covers all routine patient care costs associated with certain, qualifying clinical research trials.

How are people in clinical research trials protected? (top)
Federal regulations and ethical guidelines require researchers to follow strict ethical and scientific principles to help ensure participants are protected and valid results are produced. A plan of how the study will be run, which is called a protocol, requires that every researcher involved in the study follows the same ethical and scientific principles.

The study's sponsor writes the protocol. All researchers taking part in the study will use the same protocol. It describes how the study will be conducted in great detail: the number of participants to be enrolled, the amount of study drug to be used, the types of medical tests to be provided, etc.

To ensure participant safety, the protocol must be reviewed and approved by the organization that sponsors the study as well as an Institutional Review Board. This board consists of people with a variety of backgrounds and may include clergy, health professionals and members of the general public. In the review of the protocol, the board tries to help ensure that participants in the study will not be exposed to unreasonable or unethical risks .

Are there risks in clinical research trials? (top)
The process of evaluating investigational treatments involves some risks. Investigational drugs are first tested for safety in Phase I trials. These studies use a small group of volunteers to determine the best dose of the study drug. If the study drug is shown to be safe and well tolerated, it moves to Phase II and III trials, where larger numbers of participants with a specific disease receive the study treatment. Side effects can vary among participants. It is important to remember that clinical research trials can result in unexpected, sometimes dangerous, complications as well as potential therapeutic benefits.

The progress of participants in clinical research trials is monitored. Periodic reviews of test results and other statistics are carried out while the research trial is underway .

What questions should be asked about a clinical research trial? (top)
The following questions might be helpful in discussing a clinical research trial with a healthcare provider. They are adapted from the NIH booklet What Are Clinical Trials All About?

• What is the purpose of the trial?
• What kind of tests and research treatments are involved?
• What is likely to happen in my case with, or without, this new research treatment?
• What are alternative treatment options and their advantages and disadvantages?
• How might this trial affect my daily life?
• What side effects might I expect from the study?
• How long will the study last?
• Will hospitalization be required?
• Who will pay for the study treatment?
• If I were harmed as a result of the trial, what treatment would I be entitled to?
• What type of long-term follow-up care is part of this study?

What is informed consent? (top)
Before enrolling anyone in a clinical research trial, the staff at the research site will explain the possible risks and benefits to potential study participants, as well as the procedures to be used in the study and a participant's right to leave a study at any time. These issues are summarized in an informed consent document. All clinical research trial participants are asked to read, understand, and sign the consent document before beginning the study. It is important to ask the study site staff to explain anything that is unclear.

What are eligibility criteria (inclusion and exclusion criteria)? (top)
Participants in a research study must meet the eligibility criteria (inclusion and exclusion criteria) that are outlined in the protocol. These criteria, which differ from trial to trial, include such characteristics as gender, age, health problems, and previous or current treatments. These criteria help exclude those who might be harmed by the study drugs (such as pregnant women) or other procedures involved in the research. These criteria also help to produce scientifically reliable results by making sure that the study only enrolls certain types of patients (for example, patients with certain disease characteristics). This allows researchers to determine the benefits and disadvantages of the study drug more accurately. For example, the study treatment may be effective for one type of a disease but not another, or may be more effective in women than in men.

Can clinical research trial participants leave a trial? (top)
Yes, research study participants can leave the trial at any time for any reason. If you choose to leave the study, you will have the chance to discuss other treatments and care with your own doctor or a doctor from the study.

Do all clinical research studies involve a placebo? (top)
Not all clinical research trials involve the use of a placebo (a substance that looks like the study drug, but contains no active drug). Some Phase III trials may compare investigational therapies to the standard therapy used to treat the disease of question. However, in some cases, there is no standard treatment. When this is the case, the investigational treatment may be compared to a placebo. When a placebo is used, study participants are informed before they agree to take part in the study that there is a chance that they will not receive the study medication but may instead receive placebo.

What is a blinded or masked research trial? (top)
Most clinical research trials have a "treatment group" (which receives the study drug) and a "control group" (which may receive either standard treatment or placebo). In a blinded or masked study, participants are not told which group they are in. The reason for a blinded or masked study is to avoid study bias. If people expect to do better on a study drug, they may report hopeful signs to researchers simply because they want to believe they are doing better. Similarly, physicians may also be blinded to the drug a participants is receiving because, if they believe an investigational drug may work better, it may influence their report of how the participant is doing. In either case, the study drug may appear to work better than it really does. To prevent this from happening, a research study may be blinded or masked.

Why are participants "randomized" in some clinical research trials? (top)
In research trials where there is both a study treatment and a control group, participants are assigned to either group by chance. This process is called "randomization." Patients are randomized to avoid study bias. Randomization is used to help ensure that study results are influenced only by the study treatment being tested.

Is a referral from my physician required for participation in a clinical research trial? (top)
No, you do not need a referral. It is up to you to decide if you wish to participate or not. However, participants are usually encouraged to discuss participation in the study with their own physician and their family. In order to participate in a clinical research trial, you will be evaluated by the medical staff conducting the study to determine if you meet all the medical criteria. If you are eligible, the details of the trial will be explained to you.

Can clinical research trial participants still see their regular doctor? (top)
Yes. Clinical research trials do not replace normal health care. In fact, study coordinators, with participants’ permission, may update the study participants' personal doctors regularly.

What happens to the research trial information? (top)
Throughout the course of a research study, researchers collect information (data) in order to find out how well the investigational treatment is working. This information from a clinical research trial is carefully evaluated to determine whether the investigational drug is safe and effective enough to move into the next phase of study. Sometimes the results are extremely encouraging and sometimes the investigational treatment is determined to be ineffective or unsafe.

If a study drug or treatment is proven to be safe and effective after the completion of a phase III trial, the clinical research trial results will be presented to the FDA for review. If it is approved by the FDA, the investigational drug could become the new standard of care or another treatment option for physicians and patients in the future. In this way, clinical research trials help to bring new therapies to patients with a wide range of medical conditions .