Clinical Trials: Cutting-Edge Care

Participating in a clinical trial can yield big benefits for cancer patients, but it's important to know the risks first.

Medically Reviewed by Ann Edmundson, MD, PhD
7 min read

For every big story or spike in the value of a pharmaceutical stock prompted by a new cancer drug, there is probably a clinical trial to thank. But just because a drug or treatment makes headlines doesn't mean it's going to suddenly be available to all who might benefit from it. In fact, attention-grabbing, experimental treatments are usually only available through controlled clinical trials for several years after their initial effectiveness has been shown.

Cancer patients often have the most to gain from participating in these clinical trials, especially if currently available treatments prove ineffective. Even so, according to the American Cancer Society, only about 4% of adult cancer patients take part in clinical trials.

Recent advances in genetics and medicine, such as the mapping of the human genome, have fueled an explosion of research into new, targeted cancer therapies that treat cancers more accurately and with fewer side effects than current methods. That means the number of clinical trials available to cancer patients is growing rapidly, and they are playing an increasingly important role in the treatment of a wide variety of cancers.

"Clinical trials have always been extremely important to the development of new agents and interventions for many years," says Mary McCabe, acting director of communication and education at the National Cancer Institute (NCI). "Now, the opportunities are growing because we are in an era where we can take advantage of advances in molecular biology to develop new agents."

Deciding whether to take part in a clinical trial is a very personal decision and one that should be thoroughly discussed with healthcare providers, family, and friends. But a clear understanding of what clinical trials are, how they work, and the potential risks and benefits of participation is a critical element in making an informed decision.

Until the 20th century, there were relatively few medicines and treatment options available for cancer. So doctors relied on their own experience and education to care for their patients. But as more and more therapies and drugs were introduced, doctors needed a way to compare treatments and see what worked best for treating particular illnesses and disease.

Clinical trials emerged in the mid-20th century as studies designed to test and often compare treatments in a particular group of people. This allowed doctors to base their decisions on what therapies worked in a large number of people rather than just a few of their own patients.

Now, new medicines or therapies must first undergo rigorous testing for safety and effectiveness in clinical trials before they are approved for use by the FDA. These trials allow researchers to determine the proper dosing of new drugs and compare how well they work with what's already available.

Only a small fraction of the drugs developed in laboratories ever make it to the clinical trial stage. Before a clinical trial begins, the drug must be evaluated in pre-clinical laboratory studies and/or in animal studies.

Clinical trials are conducted in stages called phases. A phase I trial generally involves a small number of patients (usually less than 50) and its primary goal is to determine if the treatment is safe for use in humans. Doctors closely monitor the participants to determine what is the maximum safe dose of the treatment that can be given without serious side effects.

Phase I trials are generally the most risky, and for this reason they enroll patients who have few remaining treatment options or haven't responded to currently available options.

A phase II clinical trial is larger and is used to determine if the treatment is effective. Depending on the prevalence of the type of cancer the treatment is designed for, up to 100 patients may be enrolled in a phase II clinical trial.

In a phase II trial, researchers are looking to see if the experimental treatment has a beneficial effect in a significant number of the participants. If an acceptable percentage of the patients respond well to the drug, it will go to a phase III trial.

Phase III trials are the largest and usually the longest stage of the process. In this stage, the drug or intervention is compared to the current standard of care for that particular type of cancer to determine if it works better. Several hundred patients are involved from many different regions or countries and are monitored for their response to the drug as well as any potential side effects.

Many of these phase III studies are randomized and double blinded. Randomization means that similar groups of participants are randomly selected to receive either the experimental treatment or the current standard of treatment. In a double-blinded study, neither the patient nor their doctor knows which treatment the patient receives. This is done to eliminate any potential biases the doctor or patient might have.

A placebo -- an inactive ingredient or pill -- may be used in a phase III trial to determine if adding another agent to the current treatment produces a better result than the standard treatment alone. But even the placebo group always receives at least the current standard of care. Only very rarely are there cases in which there is a "no treatment" placebo group in cancer clinical trials.

The benefits of participating in a clinical trial can be both personal and altruistic.

"Personally, you may be among the first to benefit from something new and you may have more interactions with doctors and nurses," says McCabe of the NCI, which sponsors the majority of cancer clinical trials in the U.S.

Clinical trials can be an especially valuable treatment alternative for people who have hard-to-treat cancers or advanced cancers that haven't responded to current treatments.

On another level, Donald Small, MD, PhD, associate professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, says participating in a clinical trial is one way to help out other cancer patients in the future, as well as society as a whole.

"We would have never gotten to the point we are now if not for the generosity of people who have gone on clinical trials in past," Small tells WebMD.

Potential risks from participating in a clinical trial generally stem from the newness of the drug and not knowing exactly how it might affect humans alone or in combination with other treatments. Although the new therapies have been tested for side effects in animals (in the case of phase I trials) or in small numbers of people (in phase II and III trials), new side effects may emerge in certain patients when the agents are used more widely.

McCabe says, "One of the most important things to understand is that clinical trials are research and with research comes certain uncertainties. There may be risks, both known and unknown."

Although there have been rare cases of patient deaths involving clinical trials, experts say the vast majority of clinical trials have impeccable safety records.

In clinical trials, statisticians periodically review data on cure rates and side effects. If at any time the side effects go beyond normally expected limits, or if the risks outweigh the benefits of the experimental treatment, the study will be called to a halt or modified.

In addition, participation in a clinical trial is always voluntary. A participant may withdraw at any time.

Talking with your own healthcare providers is a good place to start. They might be aware of clinical trials that you might be eligible for in your area.

The National Cancer Institute also has a section on its web site devoted to clinical trials at

In addition, most types of cancers have societies associated with them that act as information clearinghouses and advocates for those patients. Many of these organizations have data on ongoing clinical trials available on their web sites.

Small, who is also a pediatric oncologist, says that the NCI-sponsored Children's Oncology Group encourages the enrollment of all children with cancer in clinical trials in order to continue to improve treatments.

He says parents must often make the decision for young children with cancer, but even young children should have an understanding of why they are undergoing treatment.

"For kids, the unknown is worse than anything," says Small. "We recommend that parents talk to kids and help them realize why it's important to take medicine. But some parents need to know when to quit."

In general, experts say it's important to find out the following information when considering participation in a cancer clinical trial:

  • Why is this study being done?
  • How will the drug/intervention be given?
  • Is hospitalization required?
  • If the study is only being conducted in certain areas, will travel be required? How often? For how long?
  • What side effects have already been found in animals or in people if it's a phase II or II trial?
  • How will this treatment affect my daily life?
  • Will insurance cover the cost of the trial?
  • If there are costs not covered by insurance, will the trial sponsors cover them?
  • How long will the study last?
  • Can I continue to receive the drug after the trial ends?
  • Are there others who are currently participating in the trial that I can talk to?

Aside from trials that test new medications and interventions for cancer, known as treatment trials, there are also other types of clinical trials of interest to cancer patients:

  • Prevention trials -- Test new approaches to lowering risks of cancer through diet, exercise, medication, and other means in people who have never had cancer.
  • Screening trials -- Test new ways to find and diagnose cancers, especially at earlier, more treatable stages.
  • Quality-of-life trials -- Look at ways to improve the quality of life of cancer patients.