Clinical Trials

Updated on 9/16/09

Clinical trials are research studies involving people. They are vitally important in the development of new strategies for preventing, diagnosing, and treating diseases. Many of today's standard treatments—those that are widely accepted and used by medical experts—are based on the results of previous clinical trials. Most clinical trials study new drugs or procedures, but some focus on drugs or procedures that have already received approval by the U.S. Food and Drug Administration.

All patients who participate in clinical trials are volunteers. They can choose to stop their participation in a clinical trial at any time.

This section of our website concerns treatment—or "therapeutic"—clinical trials for cancer patients. However, some of the information may be accurate for nontreatment trials and trials investigating treatments for other diseases.

1. What are the types of clinical trials?
2. Who are the members of the clinical trial team?
3. What are the phases of clinical trials?
4. How are patients protected?
5. How will you know if you are eligible to participate?
6. What are the potential risks and benefits of participating?
7. Will you have to pay to participate in a clinical trial?
8. Questions to ask about a clinical trial
9. Who sponsors clinical trials?
10. What happens to your personal medical information and the study results?

What are the types of clinical trials?

As you research and learn about clinical trials, you may come across different types of trials:

• Prevention trials study how healthy people may lower their cancer risk. People who are at high risk of getting cancer may benefit from participation in a prevention trial.
• Early-detection/screening trials discover ways to find early-stage cancer.
• Diagnostic trials find new and better ways to determine if someone has cancer—and, if so, where the cancer is located in the body, how much cancer is there, and whether it has spread to other parts of the body.
• Therapeutic/treatment trials study how specific anticancer treatments affect the patients who receive them.
• Quality of life/supportive care trials seek to improve the comfort and quality of life of patients and their families or caregivers.

Who are the members of the clinical trials team?

Principal investigator: Usually a doctor, the principal investigator, or PI, is responsible for the design, development, and conduct of the clinical trial. He or she evaluates data and helps participating doctors manage the trial. (Patients continue seeing their primary doctors if they are not the principal investigator.)

Research nurse: The research nurse directs and coordinates patient care during a clinical trial. The research nurse will: 1. tell you about participation in the clinical trial; 2. make sure the protocol's instructions are followed; 3. teach you about side effects of procedures and treatments used in the trial; and 4. help manage the data generated by the trial. The research nurse is a good contact for patients who have questions during a clinical trial.

Clinic nurse: The clinic nurse provides general patient care. He or she will meet with you during your doctor visits. Because the clinic nurse is a part of your healthcare team, you also may ask him or her questions.

What are the phases of clinical trials?

After promising treatments are explored in animal and/or laboratory studies, researchers perform clinical trials. Once the drug, device, or procedure enters the clinical trials process, it must go through several phases:

• Phase I trials determine the safety of a new treatment.
• Phase II trials determine whether a certain kind of cancer responds to a new treatment.
• Phase III trials study whether a new treatment is better than standard treatment.
• Phase IV trials find more information about a new treatment that has been already approved for use in patients.

Phase I Trials—Determining safety.

The goal of a Phase I trial is to find the safest dose of a new drug that patients can receive without creating side effects that would be too harmful for the patients. During a Phase I trial, the researcher also examines the best way to give a new drug, such as by mouth or intravenously (through a vein). Also, Phase I trials see if the new treatment prevents cancer from growing.

Phase I trials usually include 15 to 30 patients who are divided into small groups. These groups are called cohorts. The first cohort receives a low dose of the new drug. Doctors may collect blood or urine samples to measure drug levels in the patients.

If the first cohort does not have any severe side effects, then a new cohort receives a higher dose of the same drug. The dose increases with each new cohort until the doctors find the safest effective dose. With each increasing dose, doctors test each patient to see if he or she is responding to the treatment.

If the doctors find that the treatment is safe, then it will move forward to be studied in a Phase II trial.

Usually patients who have already taken standard treatments without success and do not have other effective cancer treatment options are eligible to participate in a Phase I trial.

Phase II Trials—Determining whether the new treatment works.

The main goal of a Phase II trial is to examine how well the new treatment works to fight a certain kind of cancer. Fewer than 100 patients usually participate in a Phase II trial. In addition to evaluating how well the treatment works against the cancer, doctors continue to monitor patients' side effects. Since more patients participate in Phase II studies, researchers may discover new side effects that were not evident during the Phase I trials. If the new treatment seems to be effective against cancer in a certain percentage of patients, researchers may consider it successful enough to continue study in a Phase III clinical trial.

Usually patients who have already undergone chemotherapy, biotherapy, surgery, or radiation are eligible for a Phase II trial.

Phase III—Studying whether the new treatment is better than standard treatment

The goal of a Phase III trial is to determine whether a new treatment is better than, the same as, or less effective than the standard treatment for a condition.

Phase III trials may include hundreds to thousands of patients around the country or the world. In general, each patient enrolled in a Phase III clinical trial has an equal chance of participating in one of two or more arms (groups) of the study. In a clinical trial with two arms:

• One arm gets the standard treatment; this is the control group.
• The other arm gets the new treatment being tested; this is the investigational or experimental group.

Randomization. How are patients assigned to groups? The process of assigning participants to groups is called randomization. Randomization helps to avoid bias in the clinical trial. (Bias occurs when human choices or other factors not related to the treatment being tested inadvertently influence a study's results.) Neither the patient nor the doctor can choose whether the patient is in the control group or the experimental group. Regardless of which group patients are assigned to, either they will receive the best standard treatment available or the new treatment being tested, which earlier research with other patients has suggested is as good as or better than the standard treatment.

Single-blind versus double-blind trials. In single-blind studies, patients do not know whether they are in the experimental or control group. In double-blind studies, neither the patients nor the researchers know which patients are in each group (although this information is recorded and on file if needed). These approaches help researchers avoid bias in the study results.

Placebos. Do cancer patients ever receive placebos (inactive medicines) in a clinical trial? Cancer patients in a clinical trial always receive the best standard treatment available or the new treatment being tested, which earlier research with fewer patients has suggested is as good as or better than the standard treatment. A placebo is a substance that looks like medicine but is not. Cancer patients are given placebos in a randomized trial only under unusual circumstances. If a placebo is used, researchers may give patients in the control group a placebo in combination with standard treatment to compare standard treatment alone to standard treatment with a new drug.

FDA approval. The role of the U.S. Food and Drug Administration is to make sure medical treatments are safe and effective for people to use. Researchers submit their clinical trial results to the FDA, and based on the information, the FDA may approve the drug or treatment. Then it becomes available to all patients and sometimes becomes the new standard treatment.

Phase IV trials—Getting more information about the new treatment.

Phase IV clinical trials are not as common as Phase I, II, and III trials. In Phase IV trials, researchers study drugs and/or treatments that have already received FDA approval. The goal of a Phase IV trial is to study the safety and effectiveness of a drug or procedure over time.

How are patients protected?

Patients are protected through the:

1. Clinical trial protocol. A protocol is a detailed plan that explains what will be done in a clinical trial and why. It outlines how many patients will take part in the clinical trial, what medical tests they will receive and how often, and the treatment and monitoring plan. Researchers must follow the protocol approved by the research institution's Institutional Review Board.

2. Institutional Review Board. An IRB is a committee of people, such as doctors, nurses, scientists, dentists, chaplains, social workers, attorneys, and patients who are responsible for protecting clinical trial participants and making sure that the trials follow federal laws.

Before a clinical trial is allowed to begin, the IRB reviews and approves the protocol to make sure that it is based on reliable scientific evidence. The IRB attempts to ensure that the health risks that patients take on as a result of joining the trial are not out of proportion to the benefits they stand to gain if the experimental treatment is effective against their cancer

After a clinical trial begins, the IRB typically monitors the trial at least once a year and stops it if any safety concerns arise. It also may stop a clinical trial early if it becomes clear that the new treatment is much more effective than standard treatment so that all the clinical trial participants may receive the better treatment.

The FDA regulates an institution's IRBs by auditing IRB minutes, staff, and facilities every five years. FDA officials also can visit an institution at any time and review anything they choose related to clinical trials.

3. The Informed consent process. If your oncologist (cancer doctor) gives you the option of participating in a clinical trial, you will go through a process called informed consent. In this process you will learn about a specific clinical trial so that you may decide whether to participate.

The informed consent process protects patients who are offered a clinical trial because it ensures that they understand the clinical trial's plan before agreeing to participate. The researcher or nurse from the clinical trial team will review the informed consent form in detail with you. This form explains a specific clinical trial's purpose, procedures, risks, and benefits. You will be encouraged to ask questions about terms or ideas that are confusing. A family member or friend may be helpful in the meeting by listening to the explanation, asking questions, and recording answers. Some oncologists also encourage patients to bring tape recorders so that they can review the information afterward. You can take the informed consent form with you to take time to think about whether you would like to participate in the clinical trial.

This section has more on:

• Information often found on the consent form
• Signing the form

Information often found on the consent form

Informed consent forms all differ, but they should include:

• The reason for the clinical trial (what the researchers hope to learn)
• Who is eligible to take part in the clinical trial
• What is known about the type of treatment being studied
• The possible risks and benefits (based on what is known so far)
• Other treatments that may be available to the patient, including non-investigational treatments
• The clinical trial's design (randomized, single-blind, double-blind, etc.)
• Types of tests, the number of tests, and doctor's visits required
• Who is responsible for the costs of the clinical trial (tests, doctor's visits, etc.)
• Who is responsible for the costs if a patient needs additional care as a result of the clinical trial
• A statement about conflicts of interest, such as whether the principal investigator has invented the therapy or has a financial stake in the company producing a medical device being tested in the trial
• A statement about protecting the patient's privacy
• A statement about the clinical trial being voluntary and the patient's rights to leave the clinical trial at any time
• Contact information for further questions

Signing the form

If you still want to participate in a clinical trial after learning all that is involved and what would be expected of you, then you will be asked to sign a consent form, one copy of which you will keep. The informed consent process does not end once you sign the form, however. If new benefits, risks, or side effects are found during a trial, the doctor must inform all the participants in the trial. Moreover, you should feel free to keep asking questions throughout the trial.

How will you know if you are eligible to participate?

Each clinical trial has eligibility criteria. Eligibility criteria are requirements that patients must meet before they can participate. Such criteria might pertain to:

• Age and sex
• Type of cancer
• Stage (extent) of the cancer
• Previous treatments that you must, or must not, have had
• Length of time since you last received treatment
• Results of certain laboratory tests
• Medicines that you are taking
• Other medical conditions
• Previous history of any other cancer

If you have found a clinical trial that might make sense for you, talk to your doctor to see if you qualify, or contact the clinical trial's principal investigator or research nurse.

What are the potential risks and benefits of participating?

Each clinical trial is unique, and participating carries its own benefits and risks.

Possible benefits include:

• You may gain treatment options.
• If the new drug or treatment works, you may be among the first to benefit.
• You will be helping patients in the future.
• The trial sponsor may pay for some of your medical care or tests. Be sure to ask your doctor or the research nurse about who is responsible for these costs before agreeing to participate.

Possible risks include:

• Side effects of the treatment being tested may be worse than those of standard treatment.
• Side effects may occur that the doctor did not anticipate.
• The new treatment may turn out to be no more effective or even less effective than the standard treatment.
• As with standard treatment, the new treatment may not work for you even if it works for other patients.
• Your medical care may be more expensive than it would have been if you'd received the standard treatment. Your health insurance company may not pay for your clinical trial care or tests. So be sure to ask your doctor or the research nurse about who is responsible for these costs before agreeing to participate.
• You may have to receive all your tests and treatment at the institution conducting the clinical trial. Depending on where you live, this may require more time and money for travel.

Will you have to pay to participate in a clinical trial?

The clinical trial sponsor (whether it is the U.S. government or a company) pays for the experimental treatment, and most pay for other parts of the treatment process, such as any special testing or extra doctor visits. Some sponsors pay for travel time or travel expenses. For Medicare patients, Medicare covers the costs of procedures that patients would have even if they were not in a clinical trial (routine costs) in all government-sponsored Phase II and Phase III clinical trials. Some health insurance companies also will cover routine costs in clinical trials. You will be responsible for any costs not covered by the clinical trial sponsor or your health insurance company. Therefore, be sure to ask questions about cost before making your decision to take part in a clinical trial, especially to confirm what costs your health insurance company will cover.

Questions to ask about a clinical trial

As the patient, it is your decision whether to participate in a clinical trial. Since it is your choice, ask as many questions as you need to ask, and continue asking until you fully understand the answers. Some examples of questions you should ask about a clinical trial include:

Treatment-specific questions

• What is my prognosis? (Your prognosis is what the doctor thinks will happen with you and your cancer—your chance of recovery, the expected course of the cancer, and the length of time you will be sick.)
• What are my treatment options?
• How would the standard treatment affect my prognosis?
• In what phase is the clinical trial?
• What is the purpose of the clinical trial?
• Why do researchers believe the treatment being tested may be as or more effective than the standard treatment? Has it been tested before? In people? If so, about how many? Has anything been published about this treatment? If so, where?
• How might participation in the clinical trial affect my prognosis?
• What are the possible short-term and long-term risks and/or side effects?
• How do the possible risks, side effects, and benefits of treatment in the clinical trial compare with standard treatment?
• How often and for how long would I receive treatment?
• Who would be in charge of my care?
• Who would be my main contact if I have any problems or questions or in an emergency?
• How long would I need to remain in the clinical trial?
• Would there be any follow-up after the clinical trial?

Logistical questions

• Would I have to come to the institution conducting the trial for all treatments, tests, and procedures? How often would I have to come? How does this compare with standard treatment? (You might also ask this last question of your oncologist.)
• Where would I receive treatment?
• How long would each treatment appointment last, including pretreatments?
• What would I need to do as a participant in the trial?
• Would I be responsible for additional costs of tests or travel?

Emotional or personal questions

• How would the clinical trial affect my daily activities?
• Can you put me in touch with other people who are in the clinical trial?
• Can you put me in touch with support services if I need them?

Decision-making suggestions

After discussing questions with the doctor and/or nurse, take time to consider your options so that you feel comfortable with your decision. Some suggestions to consider when you are deciding about a clinical trial include:

• Learn as much as you can upfront. Talk to your doctor or nurse.
• List the pros and cons of your options. Determine benefits and risks that are most important to you. Is it likely that these benefits and risks will happen?
• Get your questions answered. Keep a list of all of your questions and answers, and continue to add questions to your list. Make sure you get an answer for each question from your oncologist or nurse or clinical trial healthcare team.
• Define your priorities and your role in your family or community. What or who is most important to you? Consider making a decision that helps you continue doing what is most important to you (being a parent, continuing with your job, being active in your community, etc.)
• Talk to your family and friends. Is it important for you to do what your family thinks is best? Ask opinions of people you trust.
• Consider practical issues. If you would need to travel often to participate in the trial, would someone be able to come with you? Would it be difficult for you to complete all that you are responsible for in the clinical trial? Would you dislike having to complete a patient diary if one is required? Consider the time commitment to participate in the trial.
• Think about how participating in a clinical trial would make you feel. What decision would give you the least amount of stress? If you qualify for a trial, how do you feel about trying an unproven or unapproved treatment?

Whatever decision you make, you have the right to receive the best care available. Your relationship with your doctor will not be changed by your decision.

Who sponsors clinical trials?

The U.S. National Cancer Institute (NCI) sponsors many clinical trials. Drug companies may also sponsor clinical trials. This is because these companies must show that their drugs and medical devices are safe and effective in order to receive FDA approval and become available to the public. Medical institutions and nonprofit organizations also sometimes sponsor clinical trials.

What happens to your personal medical information and the study results?

Researchers give patients a number or code to protect their identities. When the clinical trial results are published, patients' names are not used. The research team may access a clinical trial's information to help the clinical trial sponsor submit data to the FDA to get the treatment approved. But at no time will clinical trial staffers reveal patients' names or identifying information. If you want to read what has been published about a clinical trial that you participated in, contact your oncologist. Ask for the name of the journal, date of publication, lead author, and title of the study.