Clinical Trials: How Clinical Trials Work

Clinical trials answer specific questions, such as:

  • Is a new treatment safe?
  • Does the new treatment have a positive effect on patients' disease?
  • Is the new treatment better than the current standard treatment, or other treatments that might be available?
  • Which patients benefit the most from a new treatment?

Cancer researchers begin clinical trials of new drugs only after they have tested them in cancer cells grown in a laboratory, and in animals. Treatments that show the most promise in these early experiments are studied in clinical trials in patients.

A clinical trial that focuses on cancer may be started by the National Cancer Institute, other government agencies, academic medical centers, or private drug companies. Often, several institutions work together to conduct large trials at multiple centers. Doctors at Memorial Sloan Kettering lead many of these collaborations.

What are the different types of clinical trials?

Clinical trials can test new drugs or other improvements in caring for people with cancer. The following are the most common types of clinical trials for cancer.

  • Cancer treatment trials test new combinations of drugs, new approaches to surgery or radiation therapy, or other experimental treatments. Treatment trials are the primary focus of this review.
  • Cancer prevention trials test new ways to prevent disease in people who have never had cancer, or to stop it from coming back in people who have. These approaches may include medicines, vaccines, vitamins, or lifestyle changes.
  • Diagnostic trials study new tests for understanding an individual person's disease.
  • Screening trials test the best way to detect cancer.
  • Quality-of-life trials (also called supportive care trials) explore ways to improve comfort for patients living with cancer.

What are the phases of a clinical trial?

Clinical trials that evaluate new drugs are classified by phase. The phase of a clinical trial depends on the questions that the doctors are trying to answer. Each phase can take a long time to show that a new treatment is safe or works better than an established one.

Phase I Clinical Trials

The first step in testing a new drug is called a phase I trial. A phase I trial is the first time that a new experimental therapy is tested in humans. In general, a phase I trial studies

  • whether the new experimental treatment is safe
  • the best way to give a new experimental treatment; for example, by mouth or through a blood vessel
  • how much of a new medicine should be given
  • how often it should be given

Although a phase I trial is not designed to test how effective a new therapy is, doctors are also looking for signs that it works against a particular type of cancer.

These early tests can carry significant risks. And while the treatments that are studied are sometimes effective, there is no guarantee that they will work. For these reasons, phase I studies usually only involve a small group of 20 to 80 patients who have not been helped by standard treatments.

The first few people in a phase I study usually get a low dose of the new treatment. If there are only minor side effects, or none at all, the next few patients will get a slightly higher dose. This process continues until doctors find the dose that is most likely to work without causing severe side effects.

The information gained from the results of a phase I trial is important for the design of later studies.

Phase II Clinical Trials

When a new treatment is found to be safe in a phase I trial, it usually moves to a phase II trial. Here, doctors typically study how well it works in a group of up to 100 patients with a similar type of cancer. Patients are treated using the dose and method found to be safest and most effective in phase I studies. In a phase II clinical trial, all patients usually get the same dose.

Some phase II studies randomly assign patients to one of two treatment groups, each of which receives a different experimental treatment. This is called randomization. These groups may receive different treatments, different doses of the same drug, or the same treatment delivered in different ways. Randomization helps doctors learn which approach provides the best balance of safety and effectiveness.

Doctors evaluate the results of phase I and II clinical trials to decide whether the new approach continues to look promising. If it is found to be safe and effective, researchers may proceed to a phase III trial.

Phase III Clinical Trials

Phase III clinical trials compare new treatments with standard treatments, or compare new treatments with medical records from a group of patients who were observed in the past. In phase III trials, researchers are trying to see which approach is safer and more effective.

Phase III trials usually involve a much larger group of patients than phase I or II trials. A phase III trial can include hundreds to thousands of patients. Each participant is randomly assigned to receive either the new treatment or standard therapy. In phase III studies, doctors look for more than just how the treatment affects the cancer. They also look to see whether the new treatment gives patients a longer life, a better quality of life, and fewer side effects, with fewer cases of cancer returning than standard treatment.

In some cases, a phase III clinical trial can be stopped if the researchers notice that one group is doing significantly better than the other. If a drug is successful in a phase III trial, the researchers may apply to the US Food and Drug Administration (FDA) to market it for doctors to treat the general public.

Phase IV Clinical Trials

After the FDA approves a treatment, it may be studied further in a phase IV trial. Phase IV trials evaluate the side effects, risks, and benefits of a drug or other therapy over a long period of time and in a larger number of people than in phase III trials. Thousands of people are involved in a phase IV trial, and randomization is generally not used.

Memorial Sloan Kettering Cancer Center does not perform phase IV clinical trials.

Who is eligible to participate in a clinical trial?

Every clinical trial has guidelines called eligibility criteria that specify who can and cannot participate. To ensure the most reliable results, participants in a clinical trial must be alike in key ways.

Examples of eligibility criteria for a cancer treatment trial include:

  • the type of cancer you have
  • the stage of your cancer (how advanced the cancer is)
  • your age
  • your gender
  • what other treatments you are receiving now or have received in the past

In most cases, clinical trials are open to all people who meet the eligibility criteria, regardless of your race, ethnicity, or socioeconomic background. Diversity is important to clinical trials to ensure that the new treatment is safe and effective for all people, and that everyone can benefit from the latest scientific and medical advances.

The eligibility criteria for a clinical trial are outlined in its protocol. A protocol is a document for doctors that explains all of the details about a clinical trial. Your doctor can review a protocol and help to determine whether you are eligible for a particular clinical trial.

Who oversees clinical trials?

Every clinical trial has a principal investigator (PI), a doctor who is in charge of all aspects of the study.

All institutions that receive financial support for clinical trials from the US government must also have an institutional review board, or IRB. An IRB is an independent committee of physicians, researchers, statisticians, community advocates, and others who ensure that a clinical trial is ethical. This makes sure that the risks of the clinical trial are as low as possible, that the potential benefits are greater than any risks, and that any patient who joins the trial is fully protected.

The Institutional Review Board at Memorial Sloan Kettering:

  • reviews all clinical research studies before activation (enrollment)
  • may approve, require changes to, or deny any clinical trial that involves human beings
  • ensures that all participants in a clinical trial understand what will happen
  • reviews all documents related to clinical trials at Memorial Sloan Kettering
  • monitors every trial from beginning to end, including an annual review to ensure the study is progressing well

How do I find out what's involved in a clinical trial?

Clinical trials follow a carefully controlled protocol, a plan of action that describes what researchers will do in the study. The plan is designed to protect patients' health and to answer specific questions.

Before you enroll in a clinical trial, the researchers directing the study must provide you with all of the information in the protocol. They will explain to you the trial's purpose, how long it will take, what will happen, and all potential risks and benefits. This conversation is known as informed consent. Informed consent continues throughout the trial, and is monitored by our Institutional Review Board.

What if I have trouble understanding English?

If English is not your first language, Memorial Sloan Kettering's Language Assistance Program has medical interpreters on staff who can help you understand the details of a clinical trial.

What are my rights if I participate in a clinical trial?

During the informed consent process, you will be informed of your rights. These rights include:

  • The decision to take part in a clinical trial is entirely your decision. No one can force you to participate.
  • You can withdraw from a clinical trial at any time.
  • If you decide to withdraw, the quality of your medical care at Memorial Sloan Kettering will not be affected.
  • You will be told about important new findings and about any changes in the study.
  • Your privacy is protected. Your name and other personal information will not be shared outside of Memorial Sloan Kettering without your written permission, unless the law requires it.
  • You will be informed of any standard treatment options that are available for your type of cancer. You will also be told about any other clinical trials for which you might be eligible.

What is randomization?

To study whether a new treatment is better than the standard therapy, a phase III trial usually assigns participants to one of two groups. This process is called randomization. In most cases, one group receives the current standard treatment. The other receives the new treatment. In this way, researchers can tell how effective the new drug or therapy is and compare it to the current standard of care. Some phase III studies compare two new treatments.

Randomization ensures that every patient in a clinical trial has a fair and equal chance of receiving either the new treatment or the current standard treatment. The goal of randomization is to have two groups with roughly the same characteristics, such as age and sex. At the end of the trial, if one group has a better outcome than the other, the researchers can be fairly certain that one treatment is better than the other.

In a double-blind study, neither you nor your doctor knows which treatment you are receiving. This reduces the risk of bias when doctors evaluate results and helps make the study results more credible.

If a clinical trial is a randomized, double-blind study, you will be notified during the informed consent process, before you decide whether you want to join.

What is a placebo?

If you are considering whether to join a clinical trial you may be concerned about receiving a placebo. A placebo is usually a pill, a liquid, or a powder that looks exactly like the treatment being studied, but has no effect. In a double-blind, randomized trial that uses a placebo, even your doctor will not know if you are receiving a placebo or the drug being studied.

Most cancer-related clinical trials do not use a placebo. However, some trials use a placebo because it is the only way to tell whether a new treatment works. If a trial requires that some participants receive a placebo, you will be told during the informed consent process, before you decide if you want to join.

All participants in a clinical trial, including those who receive a placebo, receive a high level of care. In addition, a clinical trial can be stopped at any point if the researchers notice that one group is doing significantly better than the other.

For example, a trial to determine whether a drug called tamoxifen could prevent breast cancer was stopped when doctors observed that the women in the trial who took tamoxifen developed fewer cancers. All participants who had been taking a placebo were immediately informed that they could switch to the active drug.