Clinical trials for cancer are research studies that test new ways to prevent, detect, diagnose, or treat cancer and other diseases in humans.
Clinical trials have and continue to help cancer survivors live longer and have a better quality of life. Because of research through clinical trials, scientists and cancer researchers have been able to translate discoveries into new treatments for cancer.
About Clinical Trials for Cancer
- Clinical trials for cancer are research studies that involve people and test new ways to prevent, detect, diagnose, or treat cancer and other diseases.
- Every clinical trial has a protocol that describes what will be done in the trial, how the trial will be conducted, and why each part of the trial is necessary.
- Regulations and policies have been developed to protect the rights, safety, and wellbeing of people who take part in clinical trials. These policies ensure trials are conducted according to strict scientific and ethical principles.
- Informed consent is a process in which people learn the important facts about a clinical trial to help them decide whether or not to take part in it, or whether to continue participating in it.
- Why are there clinical trials?
Clinical trials are research studies in which people help doctors find ways to improve health and cancer care. Each study tries to answer scientific questions and to find better ways to prevent, diagnose, or treat cancer.
A clinical trial is one of the final stages of a long and careful cancer research process. Studies are done with cancer patients to find out whether new approaches to cancer prevention, diagnosis, and treatment are safe and effective.
- What are the different types of clinical trials?
- Treatment trials test new treatments. New treatments for cancer may include a new cancer drug, new approaches to surgery or radiation therapy, new combinations of treatments, or new treatment methods such as immunotherapy.
- Prevention trials test new approaches to cancer prevention. New approaches may include medicines, vitamins, minerals, or other supplements that doctors believe may lower the risk of a certain type of cancer. These trials look for the best way to prevent cancer in people who have never had cancer, prevent cancer from coming back or prevent a new cancer from occurring in people who have already had cancer.
- Screening trials test the best way to find cancer, especially in its early stages.
- Quality of life trials (also called supportive care trials) explore ways to improve comfort and quality of life for cancer patients.
- What are the phases of clinical trials?
Most clinical research that involves the testing of a new drug progresses in an orderly series of steps, called phases.
Phases allow researchers to ask and answer questions in a way that results in reliable information about the drug and protects the patients.
Most clinical trials are classified into one of three phases:
Phase I clinical trials
These first studies in people evaluate how a new drug should be given (by mouth, injected into the blood, or injected into the muscle), how often, and what dose is safe. A phase I trial usually enrolls only a small number of patients, sometimes as few as a dozen.
Phase II clinical trials
A phase II trial continues to test the safety of the drug, and begins to evaluate how well the new drug works. Phase II studies usually focus on a particular type of cancer.
Phase III clinical trials
These studies test a new drug, a new combination of drugs, or a new surgical procedure in comparison to the current standard. A participant will usually be assigned to the standard group or the new group at random (called randomization). Phase III trials often enroll large numbers of people and may be conducted at many doctors' offices, clinics, and cancer centers nationwide
In addition, after a treatment has been approved and is being marketed, the drug's maker may study it further in a phase IV trial. The purpose of phase IV trials is to evaluate the side effects, risks, and benefits of a drug over a longer period of time and in a larger number of people than in phase III clinical trials. Thousands of people are involved in a phase IV trial.
- Are there different types of cancer clinical trials?
Yes. Cancer clinical trials differ according to their primary purpose. They include the following types:
- Treatment. These trials test the effectiveness of new treatments or new ways of using current treatments in people who have cancer. The treatments tested may include new drugs or new combinations of currently used drugs, new surgery or radiation therapy techniques, and vaccines or other treatments that stimulate a person's immune system to fight cancer. Combinations of different treatment types may also be tested in these trials.
- Prevention. These trials test new interventions that may lower the risk of developing certain types of cancer. Most cancer prevention trials involve healthy people who have not had cancer; however, they often only include people who have a higher than average risk of developing a specific type of cancer. Some cancer prevention trials involve people who have had cancer in the past. These trials test interventions that may help prevent the return (recurrence) of the original cancer or reduce the chance of developing a new type of cancer
- Screening. These trials test new ways of finding cancer early. When cancer is found early, it may be easier to treat and there may be a better chance of long-term survival. Cancer screening trials usually involve people who do not have any signs or symptoms of cancer. However, participation in these trials is often limited to people who have a higher than average risk of developing a certain type of cancer because they have a family history of that type of cancer or they have a history of exposure to cancer-causing substances (e.g. cigarette smoke).
- Diagnostic. These trials study new tests or procedures that may help identify, or diagnose, cancer more accurately. Diagnostic trials usually involve people who have some signs or symptoms of cancer.
- Quality of life or supportive care. These trials focus on the comfort and quality of life of cancer patients and cancer survivors. New ways to decrease the number or severity of side effects of cancer or its treatment are often studied in these trials. How a specific type of cancer or its treatment affects a person's everyday life may also be studied.
- Who manages clinical trials?
Every clinical trial is managed by a research team that includes doctors, nurses, research assistants, data analysts and other specialists. The research team works closely with other health professionals, including other doctors and nurses, laboratory technicians, pharmacists, dietitians, and social workers, to provide medical and supportive care to people who take part in a clinical trial.
The research team closely monitors the health of people taking part in the clinical trial and gives them specific instructions when necessary. To ensure the reliability of the trial's results, it is important for the participants to follow the research team's instructions. The instructions may include keeping logs or answering questionnaires. The research team may also seek to contact the participants regularly after the trial ends to get updates on their health.
- What are eligibility criteria, and why are they important?
Every clinical trial has a protocol, or action plan that describes what will be done in the trial, how the trial will be conducted, and why each part of the trial is necessary. The protocol also includes guidelines for who can and cannot participate in the trial. These guidelines, called eligibility criteria, describe the characteristics that all interested people must have before they can take part in the trial.
Eligibility criteria can include age, sex, medical history and current health status.
Eligibility criteria for cancer treatment trials often include the type and stage of cancer, as well as the type(s) of cancer treatment already received.
Enrolling people who have similar characteristics helps ensure that the outcome of a trial is due to the intervention being tested and not to other factors. In this way, eligibility criteria help researchers obtain the most accurate and meaningful results possible.
- How is the safety of clinical trial participants protected? What is an IRB?
National and international regulations and policies have been developed to help ensure research involving people is conducted according to strict scientific and ethical principles. In these regulations and policies, people who participate in research are usually referred to as "human subjects."
Clinical trials that are conducted or supported by agencies of the U.S. federal government or that evaluate new drugs or medical devices that are subject to regulation by the U.S. Food and Drug Administration (FDA) must be reviewed and approved by an Institutional Review Board (IRB). The IRB reviews all aspects of a clinical trial to make sure that the rights, safety, and well-being of trial participants will be protected. The IRB must also review ongoing trials at least yearly and, based on those reviews, can decide whether the trial should continue as initially planned or if changes should be made to improve participant protection. An IRB can stop a clinical trial if the researchers are not following the protocol or if the trial appears to be causing unexpected harm to the study participants.
An IRB must have at least five members, including one scientist, one person who is not a scientist, and one person who is not affiliated with the institution where the trial is taking place and who is not an immediate family member of someone who is affiliated with that institution. The non-scientist and the non-affiliated member can be the same person. IRBs can also include doctors, nurses, social workers, chaplains, patient advocates, and other health care or community professionals. All members of an IRB are required to be educated about the IRB's purpose, functions, and responsibilities, as outlined in federal regulations. Trials taking place at multiple locations can involve multiple IRBs.
- What is a Data and Safety Monitoring Board?
In addition, some clinical trials, especially phase III clinical trials, use a Data and Safety Monitoring Board (DSMB) to monitor the safety and progress of the trials. In contrast with IRBs, each trial has only one DSMB.
A DSMB is a committee of doctors, statisticians, and others who are independent of the people, organizations, and institutions that are sponsoring, organizing, and conducting the clinical trial. Similar to IRBs, DSMBs review the progress of a clinical trial and participant safety, but they also review data on the effectiveness of the trial interventions. DSMB members are experts in clinical research and clinical trials. They ensure that trial data are complete, and they can stop a trial early if safety concerns arise or if an answer to the main research question is obtained earlier than expected. Stopping a trial early because the main research question has been answered may make it possible for people who are not in the trial to get access to an effective intervention sooner. DSMBs have scheduled meetings to review clinical data, and their meeting minutes or recommendations are forwarded to the IRBs.
- What is informed consent?
Informed consent is a process through which people:
- Learn the important facts about a clinical trial to help them decide whether or not to take part in it, and
- Continue to learn new information about the trial that helps them decide whether or not to continue participating in it.
During the first part of the informed consent process, people are given detailed information about a trial, including information about the purpose of the trial, tests and other procedures that will be required, and the possible benefits and harms of taking part in the trial. Besides talking with a doctor or nurse, potential trial participants are given a form, called an informed consent form that provides information about the trial in writing.
People who agree to take part in the trial are asked to sign the form. However, signing this form does not mean that a person must remain in the trial. Anyone can choose to leave a trial at any time -- either before it starts or at any time during the trial or during the follow-up period. I
It is important for people who decide to leave a trial to get information from the research team about how to leave the trial safely.
The informed consent process continues throughout a trial. If new benefits, risks, or side effects are discovered during the course of a trial, the researchers must inform the participants so they can decide whether or not they want to continue to take part in the trial. In some cases, participants who want to continue to take part in a trial may be asked to sign a new informed consent form.
- What does a trial's "phase" mean?
New interventions are often studied in a stepwise fashion, with each step representing a different "phase" in the clinical research process. The following phases are used for cancer treatment trials.
- Phase 0
Phase 0 trials represent the earliest step in testing new treatments in humans. In a phase 0 trial, a very small dose of a chemical or biologic agent is given to a small number of people (approximately 10-15) to gather preliminary information about how the agent is processed by the body (pharmacokinetics) and how the agent affects the body (pharmacodynamics). Because the agents are given in such small amounts, no information is obtained about their safety or effectiveness in treating cancer. Phase 0 trials are also called micro-dosing studies, exploratory Investigational New Drug (IND) trials, or early phase I trials. The people who take part in these trials usually have advanced disease, and no known, effective treatment options are available to them.
- Phase I (also called phase 1)
Phase 1 trials are conducted mainly to evaluate the safety of chemical or biologic agents or other types of interventions (e.g., a new radiation therapy technique). They help determine the maximum dose that can be given safely (also known as the maximum tolerated dose) and whether an intervention causes harmful side effects. Phase 1 trials enroll small numbers of people (20 or more) who have advanced cancer that cannot be treated effectively with standard (usual) treatments or for which no standard treatment exists. Although evaluating the effectiveness of interventions is not a primary goal of these trials, doctors do look for evidence that the interventions might be useful as treatments.
- Phase II (also called phase 2)
Phase 2 trials test the effectiveness of interventions in people who have a specific type of cancer or related cancers. They also continue to look at the safety of interventions. Phase II trials usually enroll fewer than 100 people but may include as many as 300. The people who participate in phase II trials may or may not have been treated previously with standard therapy for their type of cancer. If a person has been treated previously, their eligibility to participate in a specific trial may depend on the type and amount of prior treatment they received. Although phase 2 trials can give some indication of whether or not an intervention works, they are almost never designed to show whether an intervention is better than standard therapy.
- Phase III (also called phase 3)
Phase 3 trials compare the effectiveness of a new intervention, or new use of an existing intervention, with the current standard of care (usual treatment) for a particular type of cancer. Phase III trials also examine how the side effects of the new intervention compare with those of the usual treatment. If the new intervention is more effective than the usual treatment and/or is easier to tolerate, it may become the new standard of care.
Phase 3 trials usually involve large groups of people (100 to several thousand), who are randomly assigned to one of two treatment groups, or "trial arms":
- A control group, in which everyone in the group receives usual treatment for their type of cancer, or
- An investigational or experimental group, in which everyone in the group receives the new intervention or new use of an existing intervention.
The trial participants are assigned to their individual groups by random assignment, or randomization. Randomization helps ensure that the groups have similar characteristics. This balance is necessary so the researchers can have confidence that any differences they observe in how the two groups respond to the treatments they receive are due to the treatments and not to other differences between the groups.
Randomization is usually done by a computer program to ensure that human choices do not influence the assignment to groups. The trial participants cannot request to be in a particular group, and the researchers cannot influence how people are assigned to the groups. Usually, neither the participants nor their doctors know what treatment the participants are receiving.
People who participate in phase III trials may or may not have been treated previously. If they have been treated previously, their eligibility to participate in a specific trial may depend on the type and the amount of prior treatment they received.
In most cases, an intervention will move into phase 3testing only after it has shown promise in phase 1 and phase 2 trials.
- Phase IV (also called phase 4)
Phase 4 trials further evaluate the effectiveness and long-term safety of drugs or other interventions. They usually take place after a drug or intervention has been approved by the FDA for standard use. Several hundred to several thousand people may take part in a phase 4 trial. These trials are also known as post-marketing surveillance trials. They are generally sponsored by drug companies.
Sometimes clinical trial phases may be combined (e.g., phase 1/2 or phase 2/3 trials) to minimize the risks to participants and/or to allow faster development of a new intervention.
Although treatment trials are always assigned a phase, other clinical trials (e.g., screening, prevention, diagnostic, and quality-of-life trials) may not be labeled this way.
- Are placebos used in cancer treatment clinical trials?
The use of placebos as comparison or "control" interventions in cancer treatment trials is rare.
If a placebo is used by itself, it is because no standard treatment exists. In this case, a trial would compare the effects of a new treatment with the effects of a placebo.
More often, however, placebos are given along with a standard treatment. For example, a trial might compare the effects of a standard treatment plus a new treatment with the effects of the same standard treatment plus a placebo.
- What are some of the possible benefits of taking part in a clinical trial?
The benefits of participating in a clinical trial include the following:
- Trial participants have access to promising new interventions that are generally not available outside of a clinical trial.
- The intervention being studied may be more effective than standard therapy. If it is more effective, trial participants may be the first to benefit from it.
- Trial participants receive regular and careful medical attention from a research team that includes doctors, nurses, and other health professionals.
- The results of the trial may help other people who need cancer treatment in the future.
- Trial participants are helping scientists learn more about cancer (e.g., how it grows, how it acts, and what influences its growth and spread).
- What are some of the potential harms associated with taking part in a clinical trial?
The potential harms of participating in a clinical trial include the following:
- The new intervention being studied may not be better than standard therapy, or it may have harmful side effects that doctors do not expect or that are worse than those associated with standard therapy.
- Trial participants may be required to make more visits to the doctor than they would if they were not in a clinical trial and/or may need to travel farther for those visits.
- Health insurance may not cover all patient care costs in a trial.
- Who pays for the costs of care for people in clinical trials?
The costs of care for people participating in a clinical trial fall into two general categories: routine care costs and research costs.
Routine care costs are costs associated with treating a person's cancer whether or not they are in a trial. These costs are usually covered by health insurance, but requirements vary by state and type of health plan.
Research costs are costs associated with conducting a clinical trial; these costs may include the costs of extra doctor visits, extra tests, and procedures that are required for the trial but would not be part of routine care. Research costs are usually covered by the organization that sponsors the trial.
It is important to investigate how the costs of care will be covered before participating in a clinical trial.
- What happens when a clinical trial is over?
After a clinical trial is completed, researchers look carefully at the data collected during the trial to understand the meaning of the findings and to plan further research. After a phase I or phase II trial, the researchers decide whether or not to move on to the next phase or stop testing the intervention because it was not safe or effective. When a phase III trial is completed, the researchers analyze the data to determine whether the results have medical importance and, if so, whether the tested intervention could become the new standard of care.
The results of clinical trials are often published in peer-reviewed scientific journals. Peer review is a process by which cancer research experts not associated with a trial review the study report before it is published to make sure that the data are sound, the data analysis was performed correctly, and the conclusions are appropriate. If the results are particularly important, they may be reported by the media and discussed at a scientific meeting and by patient advocacy groups before they are published in a journal. Once a new intervention has proven safe and effective in a clinical trial, it may become a new standard of care.
The FDA Amendments Act of 2007 requires that researchers report the "basic" results of clinical trials that tested FDA-regulated and FDA-approved chemical or biologic agents or medical devices in ClinicalTrials.gov, a publicly accessible database maintained by the U.S. National Library of Medicine (NLM). Basic trial results must be submitted whether or not the results are published in a peer-reviewed scientific journal and include the following items:
- Demographic and baseline information about the participants
- The progress of the participants through each stage of the trial (e.g., the number of participants who left the trial and at which stage)
- Results for the primary and secondary outcomes (also called endpoints) measured in the trial (e.g., tumor response, disease-free survival, overall survival, quality of life, etc.)
- A point of contact for the trial (to obtain additional information about the trial and its results)
More information is available on the About the ClinicalTrials.gov Results Database page.
NLM's website also has an FAQ that lists other ways to find clinical trial results.