What Are Clinical Trials?
The following data has largely adapted from “Taking part in clinical trials, what cancer patients need to know”, published by the National Cancer Institute.
Clinical trials, also called cancer treatment or research studies, test new treatments and therapies in people with cancer. The goal of these trials is to find better ways to therapies and treatments for cancer. Clinical trials in general, seek to answer specific scientific questions to find better ways to prevent, detect, and treat diseases as well as to improve overall care for people with disease. Clinical trials may 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. 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 a particular cancer in a living being and whether it has harmful effects. Many different mammals are used in this type of research, from rats to monkeys. One of the most common models for oral cancer is the hamster cheek pouch model. Of course, treatments that work well in the lab or in animals do not always work well in people. Once a particular treatment modality proves effective in an animal model, it may then progress to human clinical trials. In these trials researchers will find out whether promising treatments are as safe and effective as they were in the animal studies.
Types of Clinical Trials
There are several different types of cancer clinical trials. Each type of trial is designed to answer different research questions:
What approaches can prevent a specific type of cancer from developing in people who have not previously had cancer?
What are new ways of finding cancer in people before they have any symptoms?
How can new tests or procedures identify a suspected cancer earlier or more accurately?
Can gene-transfer therapy be used to treat cancer?
What new treatment approaches can help people who have cancer?
What is the most effective treatment for people who have cancer?
Quality-of life and supportive care trials:
What kinds of interventions can improve the comfort and quality of life of people who have cancer?
What Happens in a Clinical Trial?
In a clinical trial, patients receive treatments which are new and innovative, though not completely proven to work or be risk free. Doctors carry out research on how the treatment affects the patients, and whether the desired results occur. While clinical trials have risks for the people who participate, each study also takes steps to protect patients.
What Is It Like To Receive Treatment in a Clinical Trial?
When you take part in a clinical trial, you receive your treatment in a cancer center, hospital, clinic, and/or doctor’s office, which has qualified to become part of the study. These doctors and institutions have had to submit a rigorous protocol for approval before they may participate in a clinical trial. Doctors, nurses, social workers, and other health professionals may be part of your treatment team. They will follow your progress closely. You may have more tests and doctor visits than you would if you were not taking part in a study. You will follow a treatment plan your doctor prescribes, and you may also have other responsibilities such as keeping a log or filling out forms about your health. Many studies continue to check on patients even after their treatment is over, and it is not uncommon to have mandatory follow-up visits well after treatment has stopped. With a new therapy or treatment, it may be some time before complete understanding of the effects are completely understood.
How Is the Research Carried Out?
In clinical trials, both research concerns and patient well being are important. To help protect patients and produce sound results, research with people is carried out according to strict scientific and ethical principles.
- Each clinical trial has an action plan (protocol) that explains how it will work.
The study’s investigator, usually a doctor, prepares an action plan for the study. The protocol, explains what will be done in the study and why. It outlines how many people will participate, what common characteristics they have (such as age, extent of disease etc.), what medical tests they will receive and how often, and the expected outcome of the protocol. Exactly the same protocol is used by each doctor that takes part in the trial. For patient safety, each protocol must be approved by the organization that sponsors the study (such as the National Cancer Institute) and the Institutional Review Board (IRB) at each hospital or other study site. This board, which includes lay people, clergy, and health professionals, reviews the protocol to try to be sure that the research will not expose patients to extreme or unethical risks.
- Each study enrolls people who are alike in key ways. Each study’s protocol describes the characteristics that all patients in the study must have. Called eligibility criteria, these guidelines differ from study to study, depending on the research purpose. They may include age, gender, the type and stage of cancer, and whether cancer patients who have had prior cancer treatment and what types of treatments those have been, or if people who have other health problems can take part. Using eligibility criteria is an important principle of medical research that helps produce reliable results. During a study, they help protect patient safety, so that people who are likely to be harmed by study drugs or other treatments are not exposed to the risk. After results are in, they also help doctors know which patient groups will benefit if the new treatment being studied is proven to work. For instance, a new treatment may work for one type of cancer but not for another, or it may be more effective for men than women.
- Cancer clinical trials include research at different phases. Each phase answers different questions about the new treatment.
Phase I trials are the first step in testing a new treatment in humans. In these studies, researchers look for the best way to give a new treatment (e.g., by mouth, IV drip, or injection? how many times a day?). They also try to find out if and how the treatment can be given safely (e.g., best dose?); and they watch for any harmful side effects. Because less is known about the possible risks and benefits in Phase I, these studies usually include only a limited number of patients, between 15 and 30, who would not be helped by other existing, known treatment modalities.Phase II trials continue to test the safety of the new treatment, and begin to evaluate how well it works against a specific type of cancer. As in Phase I, only a small number of people (less than 100) take part. In general, these participants have been treated with chemotherapy, surgery or radiation, but treatment has not been effective. It is important to remember that when a phase II trial begins, it is not yet known if the agent tested works against the specific cancer being studied. Unpredictable side effects can also occur in these trials.
Phase III trials focus on how a new treatment compares to standard treatment, (treatment currently accepted and most widely used). Researchers want to learn whether the new treatment is better than, the same as, or worse than the standard treatment. In most cases, studies move into Phase III testing only after a treatment shows promise in Phases I and II.
Phase III trials may include hundreds to thousands of people, a many clinical centers, ranging from people newly diagnosed with cancer to people with extensive disease. In Phase III trials, people are assigned at random to receive either the new treatment or standard treatment.
Phase IV trials are used to further evaluate the long-term safety and effectiveness of a treatment. Less common than phase I, II, and III trials, phase IV trials usually take place after the new treatment has been approved for standard use.
Researchers assign patients by chance either to a group taking the new treatment (called the treatment group) or to a group taking standard treatment (called the control group). This method, called randomization, helps avoid bias: having the study’s results affected by human choices or other factors not related to the treatments being tested. In some studies, researchers do not tell the patient whether he or she is in the treatment or control group (called a single blind study). This approach is another way to avoid bias, because when people know what drug they are taking, it might change the way they react. For instance, patients who knew they were taking the new treatment might expect it to work better and report hopeful signs because they want to believe they are getting well. This could bias the study by making results look better than they really were.
How Are Patients Protected?
The Informed Consent Process Informed consent, as a legal, regulatory, and ethical concept, is an integral part of research. In clinical trials, informed consent is the process of providing all relevant information about the trial’s purpose, risks, benefits, alternatives, and procedures to a potential participant, who then, consistent with his or her own interests and circumstances, makes an informed decision about whether or not to participate. The informed consent process provides people with ongoing explanations that will help them make educated decisions about whether to begin or to continue participation in a clinical trial. The process does not end with the signing of informed consent documents. If new benefits, risks or side effects are discovered during the trial, researchers must inform participants. Participants are encouraged to ask questions at any time. Before agreeing to take part in a clinical trial, participants have the right to learn everything that is involved in the trial - including all details about treatment, tests, and possible risks and benefits. The information has to be in a format and language that can be easily understood.
Why Are Clinical Trials Important?
First, cancer affects us all, whether we have it, care about someone who does, or worry about getting it in the future. Clinical trials contribute to our knowledge base, and progress against cancer. If a new treatment proves effective in a study, it may become a new standard treatment that can help many patients. Many of today’s most effective standard treatments are based on previous clinical trial study results. Examples include treatments for breast, colon, rectal, and childhood cancers. Clinical trials may also answer important scientific questions and suggest future research directions. Because of progress made through clinical trials, many people treated for cancer are now living longer. Second, the patients who take part may be helped personally by the treatment(s) they receive. They get up-to-date care from cancer experts, and they receive either a new treatment being tested or the best available standard treatment for their cancer. Of course, there is no guarantee that a new treatment being tested or a standard treatment will produce good results. New treatments also may have unknown risks. But if a new treatment proves effective or more effective than standard treatment, study patients who receive it may be among the first to benefit. Some patients receive only standard treatment and benefit from it. In the past, clinical trials were sometimes seen as a last resort for people who had no other treatment choices. Today, patients with common cancers often choose to receive their first treatment in a clinical trial.
Clinical Trials: Weighing the Pros and Cons
While a clinical trial is a good choice for some people, this treatment option has both possible benefits and drawbacks.
Clinical trials offer high-quality cancer care. If you are in a study and do not receive the new treatment being tested, you will receive the best standard treatment. This may be as good as, or better than, the new approach. If a new treatment approach is proven to work and you are taking it, you may be among the first to benefit. By looking at the pros and cons of clinical trials and your other treatment choices, you are taking an active role in a decision that affects your life. You have the chance to help others and improve cancer treatment.
New treatments under study may not be better than, or even as good as standard care. They may have side effects that doctors do not expect or that are worse than those of standard treatment. Even if a new treatment has benefits, it may not work for you. Even standard treatments, proven effective for many people, do not help everyone. If you receive standard treatment instead of the new treatment being tested, it many not be as effective as the new approach.
Health insurance and managed care providers do not always cover all patient care costs in a study. What they cover varies by plan and by study. To find out in advance what costs are likely to be paid in your case, talk to the doctor, nurse or social worker from the study.
If you have any questions about how clinical trials work, or your rights and your protections, ask your doctor, nurse, or other health professional.