Clinical trials provide the latest in medical treatments before they are made available to the general public as standard treatment. Treatments are administered under carefully controlled conditions, which allow doctors and researchers to learn about their effectiveness, as well as possible side effects. Patients are carefully selected to be sure the treatment is appropriate for their particular disease and current state of health. Participants will work with doctors and healthcare professionals at every stage of a clinical trial.

Studies at REDI start with a proposal from a REDI doctor or an outside organization. All studies are first reviewed by our department, as well as our Institutional Review Board. Only studies that seem like they would benefit patients now or in the future are considered. In the following sections, the clinical study process is described in greater detail.

Some patients who choose to participate in clinical trials hope to get a better response to treatment or increase survival by using newer drugs or therapies. Some patients feel that participation in clinical trials will help others - family, friends, or even strangers - as well as themselves. Other patients may feel they could potentially benefit from new drugs years before the drug would otherwise be available through a doctor’s prescription - and at no cost! Many patients feel the close follow-up and re-testing schedules used to check results of the treatment on a clinical trial ensures a thorough schedule of care.

Every clinical trial asks a question: Is this new equipment of benefit? Does this treatment have fewer side effects? Is this drug better? To answer these questions accurately, eligibility criteria are developed to assure that patients treated on the trial are similar in age, sex, stage of diagnosis, etc. To be eligible for a trial, you must meet these criteria. In addition, your doctor will make a decision whether to offer treatment on a particular clinical trial, based on his or her knowledge of you and your disease. While there are clinical trials available for many types of cancers and different stages of disease, clinical trials are not necessarily available or appropriate for all patient situations.

Your doctor and a research coordinator will work closely together to determine if there is a clinical trial that might be right for you, and for which you might be eligible. Your doctor may ask the research coordinator to be present during one of your office visits when treatment decisions are being made.

Having an idea of what you can expect from taking part in a study can help relieve some of your concerns and make things go more smoothly. The first thing you will need to do is give your informed consent to take part in the study.

Informed Consent

The people running the study are required to get your written, informed consent before you take part in any way (often even before you have any needed tests to see if you are eligible for the study). In the informed consent process, the researchers (doctors or nurses) will explain the details of the study to you and answer all of your questions and concerns.

You will then be given a written consent form to sign. Consent forms are not all the same, but they should include the following:

• The reason for the study (what the researchers hope to find out)
• Who is eligible to take part in the study
• What is known about the new type of treatment
• The possible risks and benefits of the new treatment (based on what is known so far)
• Other treatments that may be an option for you
• The design of the study (whether it is randomized, double-blinded, etc.)
• How many and what types of tests and doctor's visits are involved
• Who must pay for the costs of the clinical study (tests, doctor's visits, etc.) and for the costs if you need additional care as a result of the clinical study
• A statement about how your identity will be protected
• A statement about the voluntary nature of the study and your right to leave the study at any time without fear of affecting the care that you would normally get outside the study
• Contact information if you have further questions

Before you sign the consent form, ask questions. Be sure someone from the research team goes over the form with you in detail. Efforts are made for consent forms to be easy to understand, but there still may be words or ideas that are confusing to you. You may want to bring someone along with you to the meeting to make sure all your concerns are addressed.

Be sure you understand what is involved and what is expected of you. Try to explain what you heard to your doctor or nurse to make sure you got it right. Recent surveys have shown that while most people are satisfied with the informed consent process, more than half do not understand some of the main points on the consent form.

Remember, you don’t have to rush into making a decision. Take the consent form home with you if you need to. Ask trusted family members and friends what they think. If possible, you may want to get a second opinion from another doctor, too.

Taking Part in the Study

Once you've signed the consent form, you will be ready to take part in the study. You will probably need to have blood tests or imaging tests done before you start treatment. A full medical history and physical exam are also usually done. The results are needed before you start the actual study to be sure that you meet the eligibility criteria and to help ensure your safety.

In many ways, participants are treated much the same way as other patients getting treatment outside of a clinical study. However, there are some important differences.

You may have tests done more often to find out how well the treatment is going and to look out for your welfare. It is likely that you will get more attention as a study participant than you would otherwise. The doctors and nurses may examine you more often and will want to know if you are having any side effects (called adverse events) while being treated.

Because the possible complications may not fully be known, it is very important to let the research team know about anything out of the ordinary. They can then decide if symptoms you are having are related to the study, and if they need to be treated or your therapy needs to be changed.

Your participation in the study may end for any number of reasons:

• You complete treatment on the study
• The treatment does not appear to be working for you
• You have serious side effects while in the study
• The study itself is stopped early because the treatment either has proven to be effective or has proven to be too harmful in others
• You decide to leave the study

Once out of the study, you may still be watched for a time so that researchers can continue to see how you are doing.

Some studies allow you to continue to receive the new treatment even after the study ends. This is known as "open label," because you and your doctor know which treatment you are getting. This option varies among clinical studies, so be sure to ask about it before you begin.

Questions to Ask Before Participating in a Study

• How long will the study last?
• Where is the study being conducted?
• What treatments will be used and how?
• What is the main purpose of the study?
• How will patient safety be monitored?
• Are there any risks involved?
• What are the possible benefits?
• What are the alternative treatments besides the one being tested in the study?
• Who is sponsoring the study?
• Do I have to pay for any part of the study?
• What happens if I am harmed by the study?
• Can I opt to remain on this treatment, even after termination of the study?

Information to all of these questions is contained in the consent form you will receive for each clinical study. However, it is important that you ask these questions and receive the information you need to make an informed decision.

Making decisions about treatment options is always difficult. Your physician may offer several different standard treatments, as well as a clinical trial. There are ethical and legal codes governing the practice of medicine and your participation in a clinical trial.

To make a good decision, you must have all the facts. Informed consent means having a full explanation of all the potential benefits and risks of a particular therapy. You are encouraged to ask many questions, and take time to think about your options so you are comfortable with your decision. The informed consent process is an ongoing one. Whether you take part in a clinical trial or not, any questions that arise should be asked and will always be answered. If at any time you change your decision to participate in a clinical trial, you always have the right to withdraw your consent.

The clinical testing of experimental drugs is normally done in three phases, each successive phase involving a larger number of people. Even once the Food and Drug Administration has approved a new drug for market, pharmaceutical companies may still conduct post-marketing or late phase three/phase four studies. Sometimes clinical studies are called clinical trials.

A Phase I Study

Phase I studies are primarily concerned with assessing the drug's safety. This initial phase of testing in humans is done in a small number of healthy volunteers (20 to 100), who are usually paid for participating in the study. The study is designed to determine what happens to the drug in the human body—how it is absorbed, metabolized and excreted. A phase I study will investigate side effects that occur as dosage levels are increased. This initial phase of testing typically takes several months. About 70 percent of experimental drugs pass this initial phase of testing.

A Phase II Study

Once a drug has been shown to be safe, it must be tested for efficacy. This second phase of testing may last from several months to two years, and involve up to several hundred patients. Most phase II studies are randomized studies. One group of patients will receive the experimental drug, while a second control group will receive a standard treatment or placebo. Often these studies are blinded—neither the patients nor the researchers know who is getting the experimental drug. In this manner, the study can provide the pharmaceutical company and the FDA comparative information about the relative safety of the new drug and its effectiveness. Only about one-third of experimental drugs successfully complete both phase I and phase II studies.

A Phase III Study

In a phase III study, a drug is tested in several hundred to several thousand patients. This large-scale testing provides the pharmaceutical company and the FDA with a more thorough understanding of the drug's effectiveness, benefits and the range of possible adverse reactions. Most phase III studies are randomized and blinded studies.

Phase III studies can last several years. Seventy to 90 percent of drugs that enter phase III studies successfully complete this phase of testing. Once a phase III study is successfully completed, a pharmaceutical company can request FDA approval for marketing the drug.

Post-Marketing — Late Phase III/Phase IV Studies

In late phase III/phase IV studies, pharmaceutical companies have several objectives:

1. Studies often compare a drug with other drugs already on the market.
2. Studies are often designed to monitor a drug's long-term effectiveness and impact on a patient's quality of life.
3. Many studies are designed to determine the cost-effectiveness of a drug therapy relative to other traditional and new therapies.

Funding for clinical research comes from both the federal government (through the National Institutes of Health) and private industry (pharmaceutical, medical device and biotech companies). The sponsor of the research hires physicians, who may work in a wide variety of healthcare settings, to conduct the clinical study. Physicians are typically paid on a per-patient basis. The medical care is often provided at no charge to the patient. Patients may also be paid a small fee to participate in a clinical study.

Physicians and other medical professionals run studies according to strict rules set by the federal government. The U.S. Department of Health and Human Services has two offices that identify these rules: the Food and Drug Administration and the Office for Human Research Protections. These agencies have good clinical practice requirements that establish rules every clinical study must follow, such as how to conduct a study and how to protect human subjects.

The federal government has a policy that protects human subjects. This policy is called the Common Rule. It applies to all research funded by the federal government. The Common Rule says an institutional review board, or IRB, must guarantee it will provide and enforce protection for people involved in its research. The review board, which is usually composed of physicians and lay people, is charged with examining the study's protocol to ensure that the patient's rights are protected, and that the study does not present an undue or unnecessary risk to the patient.

An IRB reviews and approves the study protocol before the study can even begin; any physician awarded a research grant by a pharmaceutical company or the NIH must obtain approval to conduct the study from an IRB. Also, anyone participating in a clinical study in the United States is required to sign an IRB-approved informed consent form. This form details the nature of the study, the risks involved and what may happen to a patient in the study, and is described further in the section “What would taking part in a clinical study involve?”. The informed consent tells patients that they have a right to leave the study at any time.

Not all clinical studies investigate treatments. Many clinical studies explore new ways to detect, diagnose or learn the extent of disease. Some even look at ways to prevent the disease from happening in the first place.

Even among clinical studies that do examine treatments, not all of them study drugs. Many clinical studies test other forms of treatment, such as new surgery or radiation therapy techniques, or medical devices. A study may even test complementary or alternative medicines.

When clinical studies do look at drugs, not all of them examine new ones. Even after a drug has been approved for use against a specific condition, doctors sometimes find it works better when given a certain way or when combined with other treatments. It may even work on a different medical condition. Clinical studies are needed to look at these possibilities as well.

Many, but not all, clinical studies involve a placebo. A placebo is an inactive ingredient or pill used in some types of clinical studies to help make sure results are unbiased. A placebo is sometimes called a sugar pill. Over the years, doctors have observed that some people begin to feel better even if they just think they're being treated. With the possibility of getting a placebo, people can't tell whether they are getting the treatment being studied or not, which makes the results more likely to be valid.

Placebos are rarely used in research where known viable, effective treatments exist. It's not ethical to have someone take a placebo if an effective standard treatment is already available. When clinical studies don’t use placebos, they compare the new treatment against the current standard treatment. A study may be designed so that patients may not be told which one they are getting, but they know they are at least getting treatment that meets the current standard of care. In studies that use placebos, however, you would stand a chance of getting no treatment.

For more detailed information about participating in clinical studies, you can refer to the website of CenterWatch, a Clinical Studies Listing Service.

There's also clinical trial information available from the American Cancer Society. Although the website focuses on cancer, it has a comprehensive discussion of clinical studies.

The National Library of Medicine's Clinical Trials Website lists more than 4,000 studies available in locations across the United States, and contains information you may find helpful about the clinical trial process in general.

You can find a Glossary of clinical research terms at CenterWatch Glossary.