Human testing: Clinical trials
Clinical trials are research studies in which people volunteer to help doctors find ways to prevent or treat disease. When these kinds of studies are carefully designed and run, and are of sufficient size, they can begin to show whether a specific substance or method truly reduces cancer risk.
Clinical trials must be set up carefully and all the plans reviewed ahead of time, because they propose to change something that might affect a person’s life. Cancer prevention clinical trials must always be approved by a group whose job it is to look after the safety of the volunteers in the clinical trial. This group is called an Institutional Review Board or IRB. It’s an independent group of doctors, statisticians, and others who review human studies to be sure that the safety and well-being of the study volunteers are protected.
Researchers often design a clinical trial with a control group. That means, for example, they may give a test substance to one group of volunteers, and either a known cancer reducer or an inactive compound (called a placebo) to the other group. Or the researchers may test a method or activity in one group, like aerobic exercise 4 times a week, against a group that’s offered a different type of activity, or perhaps no special exercise sessions. Then the groups are compared later to see if one group has more cancer than the other. There are several kinds of clinical trials that give us different kinds of information.
Before tests of a substance that may prevent cancer can be done on humans, it’s important to know if the compound or method being tested is safe. The results from any animal tests on the substance, and any human studies or observations, are reviewed along with other facts that are known about it.
If the substance is a known ingredient that’s commonly found in food, it may be on the “generally recognized as safe” list, and be accepted for further testing. But if the amounts to be used are much higher than a person would usually get in food, further testing for safety may be needed. Other evidence may be weighed, too, such as the effects of related compounds, what’s already known about the class of chemicals, and other such information. If the substance or method is thought to be safe to study in this group of volunteers, the researchers must convince an Institutional Review Board (IRB) that their methods have a chance of working, that the substance or method is safe, and that study volunteers are protected from harm.
If it’s a compound that’s a new substance, the company must tell the FDA why they think it will work in humans. They must also share research from any lab and animal studies that were already done, or human toxicology studies.
If the FDA and/or the IRB approve human testing, researchers must decide how to design clinical trials and find volunteers who are willing to take the compound or the control substance.
What is a cancer prevention clinical trial?
Clinical trials are most often thought of as research studies in which volunteers with certain illnesses or conditions help doctors find ways to treat disease or improve care. A cancer prevention clinical trial (or cancer prevention study) is a different kind of clinical trial. In these, healthy volunteers help doctors find ways to lower the risk of certain types of cancer. There are different types of cancer prevention studies.
All cancer prevention clinical trials are done to answer these questions:
- Does the medicine, supplement, or other cancer prevention method work to reduce the risk of cancer?
- How safe is it to take the study agent or use the cancer prevention method?
- Does it reduce the death rate in the group that uses the cancer prevention method by reducing the number of people who get cancer?
Some prevention studies may require the volunteer to do something, like exercise for a certain length of time each day, stop smoking, eat extra fruits and vegetables, or get tests to find and remove pre-cancers. The action may either be to avoid something thought to be harmful, or to do something thought to be helpful. These are called action studies, and they help researchers find out if the actions that are taken will reduce cancer risk.
In another type of study, the volunteer must take something, such as a drug, vitamin, mineral, or food supplement, to see if it reduces their cancer risk. Scientists who conduct these studies want to learn whether the medicine or supplement (often called a study agent) reduces cancer risk. They’ll also look at the safety of the study agent. These are called agent studies or chemoprevention studies.
Cancer prevention clinical trials that involve a drug, supplement, vitamin, or mineral are set up something like the clinical trials that test new drugs. They are generally done in 3 phases, starting with phase I. Each phase is designed to answer different questions about the compound being tested:
- Phase I trials look for the best way to give the compound, the best dose, and check for any harmful side effects.
- Phase II trials look at whether the substance has an effect in preventing cancer.
- Phase III trials compare a promising new compound to one that’s already in use by giving the new one to one group and the older one to the other group (see “Control group”). If there’s no substance that’s already being used for the same purpose, the control group may get a placebo (a sham pill or supplement; see our document, “ Placebo Effect”).
These phases build on each other. If, for instance, the side effects are severe in the phase I trial, a phase II trial is not likely to be done. If phase I shows no harmful effects, a phase II study may be carried out. But if the phase II study shows no effect, a phase III trial isn’t planned, unless there’s reason to doubt the phase II outcome. The phase I part of the clinical trial is usually the smallest of the study groups, and phase III the largest. If you can find only phase I studies on a cancer prevention method, it may mean that there’s not yet good information about its use in humans.
A cancer prevention study may be done on different kinds of volunteers, depending on its purpose:
- Clinical trials that look for ways to reduce cancer risk in people who have never had cancer
- Clinical trials that look for ways reduce cancer risk in people who have already had cancer
Sometimes, a cancer prevention study may enroll volunteers from groups that are known to be at higher risk of cancer. Those at higher risk stand to benefit more from anything that helps to reduce risk. Also, if the method actually helps, it often takes less time to see if risk is lowered in those who are more likely to have cancer.
Controlled clinical trials of cancer prevention
A clinical trial is best done with at least 2 groups of people that are very much alike. This helps researchers know that any differences between the groups are actually due to the method being tested, rather than factors that the volunteers may have had when they came into the study. These 2 groups are called the intervention group and the control group. Sometimes, there are more than 2 groups, such as when 2 or more interventions are being tested against the control group. And sometimes, there are 2 control groups, one with a placebo or sham treatment, and one with no kind of intervention.
Intervention group: This is the group taking the study agent, or the group that does the action. It’s also called the test group or study group.
Control groups: In the study of a compound to prevent cancer, or agent study, the control group takes either:
- A standard agent that’s being compared with the study agent (the substance being tested)
- A look-alike pill or substance that contains no active ingredient, called a placebo
In an action study, the control group may:
- Get standard health promotion, such as information or instructions about eating or exercise
- Do something other than the action taken by the test group
- Do nothing or be put on a delayed treatment list (wait list)
No matter what the control group members do, they are watched in the same way the test group is during and after the intervention.
Protocols: Clinical trials follow strict guidelines that help make sure the science is sound and that volunteers who take part are protected. Each clinical trial has a principal investigator who is in charge of the study. Each study also has a detailed plan, called a protocol, which says what the study will do and how it will do it. The protocol explains the study design, who can and can’t be in the study, what’s being studied, what medical tests are needed and how often, and what other information will be gathered.
- Learning About New Ways to Prevent Cancer
- Look at where the information came from
- Look at the science behind the prevention method
- Types of human studies on cancer risk
- Studies that observe humans
- Human testing: Clinical trials
- A closer look at the evidence
- Other questions about studies on new ways to prevent cancer
- What does this mean to you?
- To learn more
- Appendix A