What are clinical trials?
Clinical trials, also called cancer treatment or research studies, test new treatments in people with cancer. The goal of this research is to find better ways to treat cancer and help cancer patients. Clinical trials test many types of treatment such as new drugs, new approaches to surgery or radiation therapy, new combinations of treatments or new methods such as gene therapy. A clinical trial is one of the final stages of a long and careful cancer research process.
The search for new treatments begins in the laboratory where scientists first develop and test new ideas. If an approach seems promising, the next step may be testing a treatment in animals to see how it affects cancer in a living being and whether it has harmful effects. Of course, treatments that work well in the lab or in animals do not always work well in people. Studies are done with cancer patients to find out whether promising treatments are safe and effective.
Why are clinical trials important?
Each study answers scientific questions and tries to find better ways to prevent, screen for, diagnose or treat a disease. People who take part in cancer clinical trials have an opportunity to contribute to knowledge of, and progress against, cancer. They also receive up-to-date care from experts.
What are the types of clinical trials?
Prevention trials study ways to reduce the risk, or chance, of developing cancer. Most prevention trials are conducted with healthy people who have not had cancer. Some trials are conducted with people who have had cancer and want to prevent the return of cancer or reduce the chance of developing a new type of cancer.
Screening trials study ways to detect cancer. They are often conducted to determine whether finding cancer before it causes symptoms decreases the chance of dying from the disease. These trials involve people who do not have any symptoms of cancer.
Diagnostic trials study tests or procedures that could be used to identify cancer more accurately and at an earlier stage. Diagnostic trials usually include people who have signs or symptoms of cancer.
Treatment trials are conducted with people who have cancer. They are designed to answer specific questions about, and evaluate the effectiveness of, a new treatment or a new way of using a standard treatment. These trials test many types of treatments, such as new drugs, vaccines, new approaches to surgery or radiation therapy, or new combinations of treatments.
Supportive care (or quality of life) trials explore ways to improve the comfort and quality of life of cancer patients and cancer survivors. These trials may study ways to help people who are experiencing nausea, vomiting, sleep disorders, depression or other effects from cancer or its treatment.
Genetics studies are sometimes part of another cancer clinical trial. The genetics component of the trial may focus on how genetic makeup can affect detection, diagnosis or response to cancer treatment.
Who sponsors clinical trials?
Clinical trials are sponsored by private organizations and Government agencies that are seeking better treatments for cancer or better ways to prevent, screen and diagnose cancer.
How are participants protected?
Research is conducted according to strict scientific and ethical principles. Every clinical trial has a protocol, or action plan, which acts like a “recipe” for conducting the trial. The plan describes what will be done in the study, how it will be conducted and why each part of the study is necessary. The same protocol is used by every doctor or research center taking part in the trial.
All federally funded clinical trials and trials to evaluate a new drug or medical device subject to Food and Drug Administration regulation must be reviewed and approved by an Institutional Review Board (IRB). Many institutions require that all clinical trials, regardless of funding, be reviewed and approved by a local IRB. The Board, which includes doctors, researchers, community leaders and other members of the community, reviews the protocol to make sure the study is conducted fairly and participants are not likely to be harmed. The IRB also decides how often to review the trial once it has begun. Based on this information, the IRB decides whether the clinical trial should continue as initially planned and, if not, what changes should be made. An IRB can stop a clinical trial if the researcher is not following the protocol or if the trial appears to be causing unexpected harm to the participants. An IRB can also stop a clinical trial if there is clear evidence that the new intervention is effective, in order to make it widely available.
The National Institutes of Health (NIH)-supported phase I and II clinical trials must have a data and safety monitoring plan, and all phase III clinical trials must have a Data and Safety Monitoring Board (DSMB). The DSMB is an independent committee made up of statisticians, physicians and other expert scientists. The DSMB ensures that the risks of participation are as small as possible, the data are complete and stops a trial if safety concerns arise or when the trial’s objectives have been met.
If the participants experience severe side effects, or there is other evidence that the risks outweigh the benefits, the IRB and DSMB will recommend that the trial be stopped early. A clinical trial might also be stopped if there is clear evidence that the new approach is effective --so the approach can be made widely available.
What are eligibility criteria, and why are they important?
Each study’s protocol has guidelines for who can or cannot participate in the study. These guidelines, called eligibility criteria, describe characteristics that must be shared by all participants. The criteria differ from study to study. They may include age, gender, medical history and current health status. Eligibility criteria for treatment studies often require that patients have a particular type and stage of cancer.
Enrolling participants with similar characteristics ensures that the results will be due to what is under study and not other factors. In this way, eligibility criteria helps researchers achieve accurate and meaningful results. These criteria also make certain that people who could be made worse by participating in the study are not exposed to the risk.
What is informed consent?
Informed consent is a process by which people learn the important facts about a clinical trial to help them decide whether to participate. This information includes details about what is involved, such as the purpose of the study, the tests and other procedures used in the study, and the possible risks and benefits. In addition to talking with a doctor or nurse, people receive a written consent form explaining the study. People who agree to take part in the study are asked to sign the informed consent form. However, signing the form does not mean people must stay in the study. People can leave the study at any time -- either before the study starts or at any time during the study or the follow-up period.
The informed consent process continues throughout the study. If new benefits, risks or side effects are discovered during the study, the researchers must inform the participants. They may be asked to sign new consent forms if they want to stay in the study.
Where do clinical trials take place?
Clinical trials take place in doctors’ offices, cancer centers, medical centers, community
hospitals and clinics, and veterans’ and military hospitals in cities across the United States and in other countries. Clinical trials may include participants at one or two highly specialized centers, or they may involve hundreds of locations at the same time.
How are clinical trials conducted?
Clinical trials are usually conducted in a series of steps, called phases. Treatment clinical trials are always assigned a phase. However, screening, prevention, diagnostic and supportive care studies do not always have a phase. Genetics clinical trials generally do not have a phase.
Phase I trials are the first step in testing a new approach in humans. In these studies, researchers evaluate what dose is safe, how a new agent should be given (by mouth, injected into a vein or injected into the muscle) and how often. Researchers watch closely for any harmful side effects. Phase I trials usually enroll a small number of patients and take place at only a few locations. The patients are divided into smaller groups, called cohorts. Each cohort is treated with an increased dose of the new therapy or technique. The highest dose with an acceptable level of side effects is determined to be appropriate for further testing.
Phase II trials study the safety and effectiveness of an agent or intervention, and evaluate how it affects the human body. Phase II studies usually focus on a particular type of cancer, and include fewer than 100 patients.
Phase III trials compare a new agent or intervention (or new use of a standard one) with the current standard therapy. Participants are randomly assigned to the standard group or the new group, usually by computer. This method, called randomization, helps to avoid bias and ensures that human choices or other factors do not affect the study’s results. In most cases, studies move into phase III testing only after they have shown promise in phases I and II. Phase III trials may include hundreds of people across the country.
Phase IV trials are conducted to further evaluate the long-term safety and effectiveness of a treatment. They usually take place after the treatment has been approved for standard use. Several hundred to several thousand people may take part in a phase IV study. These studies are less common than phase I, II or III trials.
People who participate in a clinical trial work with a research team. Team members may include doctors, nurses, social workers, dietitians and other health care professionals. The health care team provides care, monitors participants’ health and offers specific instructions about the study. It is important for participants to follow the research team’s instructions, so that the trial results are as reliable as possible. These instructions may include keeping logs or answering questionnaires. The research team may continue to contact participants after the trial ends.
What happens when a clinical trial is over?
After a clinical trial is completed, the researchers look carefully at the data collected during the trial before making decisions about the meaning of the findings and further testing. After a phase I or II trial, the researchers decide either to move on to the next phase, or stop testing the agent or intervention because it was not safe or effective. When a phase III trial is completed, the researchers look at the data and decide whether the results have medical importance.
The results of clinical trials are often published in peer-reviewed, scientific journals. Peer review is a process by which experts review the report before it is published to make sure the analysis and conclusions are sound. If the results are particularly important, they may be featured by the media and discussed at scientific meetings and by patient advocacy groups before they are published. Once a new approach has been proven safe and effective in a clinical trial, it may become standard practice. (Standard practice is a currently accepted and widely used approach.)
What are some of the benefits of taking part in a clinical trial?
The benefits of participating in a clinical trial include the following:
What are some of the possible risks associated with taking part in a clinical trial?
The possible risks of participating in a clinical trial include the following:
Who pays for the patient care costs associated with a clinical trial?
Health insurance and managed care providers often do not cover the patient care costs associated with a clinical trial. What they cover varies by health plan and by study. Some health plans do not cover clinical trials if they consider the approach being studied “experimental” or “investigational.” However, if enough data show that the approach is safe and effective, a health plan may consider the approach “established” and cover some or all of the costs. Participants may have difficulty obtaining coverage for costs associated with prevention and screening clinical trials; health plans are currently less likely to have review processes in place for these studies. It may, therefore, be more difficult to get coverage for the costs associated with them. In many cases, it helps to have someone from the research team talk about coverage with representatives of the health plan.
Health plans may specify other criteria a trial must meet to be covered. The trial might have to be sponsored by a specified organization, be judged “medically necessary” by the health plan, not be significantly more expensive than treatments the health plan considers standard or focus on types of cancer for which no standard treatments are available. In addition, the facility and medical staff might have to meet the plan’s qualifications for conducting certain procedures, such as bone marrow transplants.
What are some questions people might ask their health care provider before entering a clinical trial?
It is important for people to ask questions before deciding to enter a clinical trial. Some questions people might want to ask their doctor or nurse are below.
The Study
Possible Risks and Benefits
Participation and Care
Personal Issues
Cost Issues
Where can people find more information about clinical trials?
People interested in taking part in a clinical trial should talk with their health care provider.