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What Participants Need to Know About Clinical Trials

by Kenneth A. Getz, MBA, Oren Traub, MD, PhD

Clinical trials are experiments designed to find out whether an intervention is safe and effective. The intervention is most often a drug but can also be a device, such as a pacemaker or stent, or a diagnostic tool, such as a blood test. Participation in a clinical trial is an option for many people who have serious illnesses, especially when no good treatments are available. Thousands of clinical trials are conducted each year and may take place at a variety of locations, including universities, hospitals, clinics, doctors’ private offices, and professional clinical research sites.

The people who conduct clinical trials are called clinical researchers or investigators. Investigators are usually doctors who are paid to conduct the trials by the National Institutes of Health or by a pharmaceutical, biotechnologic, or medical device company. Investigators follow a detailed protocol that dictates who is eligible to participate in the trial, what interventions will be given or used, how often participants will be evaluated, and how data will be collected. Several thousand people typically participate in clinical trials for each new intervention before it becomes available to the general public.

Types of Clinical Trials

Clinical trial design can be complicated but typically follows the principles described above (see see The Science of Medicine : How Doctors Try to Learn What Works).

All interventions must be approved by the U.S. Food and Drug Administration (FDA) before they can be prescribed or used. The FDA’s goal is to allow an intervention to be given to the general public only after that intervention has proved to be safe and effective in carefully designed clinical trials. The FDA requires three phases of clinical trials before approval is granted.

A phase I trial is the first time an intervention is used on people. Tests are conducted on a small group of healthy people to learn how the intervention acts in humans, including the side effects, and to learn what doses of drugs are safe. Because phase I trials involve healthy people, the participants receive no direct medical benefit, but their contribution to the health of others is significant.

If the intervention seems safe in a phase I trial, phase II trials are conducted. In phase II trials, the intervention is tested in a larger group of people who have the disease that the intervention is intended to treat. Phase II trials help researchers determine whether the intervention is safe for sick people and give an early determination of whether the intervention is effective. If the intervention is a drug, phase II trials help researchers determine what dose might be appropriate.

If safety is still satisfactory in phase II and the intervention seems effective, a phase III trial is conducted. In phase III trials, the intervention is given to or tested in a large group of people who have the disease being studied. In phase III, the new intervention is usually compared with the standard treatment, a placebo, or both.

It takes an average of 7 years for a promising drug to make its way through the clinical testing process. Many drugs, medical devices, and diagnostic tools never complete all 3 phases. Others do complete the 3 phases but are not approved for use because they fail to be effective or safe or both. Doctors also conduct clinical trials with interventions that have already been approved for use (sometimes termed phase IV trials). These trials may be done to compare two or more interventions or to test an intervention on a different disorder. In this case, 3 phases are not needed, but the clinical trial design is similar.

The Participation Experience

People have different reasons for wanting to participate in clinical trials. Some want the newest treatments, which they hope will be more effective than the current standard of care. Others participate out of a desire to contribute to science. Still others may want access to free drugs and medical care.

Merely wanting to be in a clinical trial is not enough. Only people who are eligible for a particular trial can participate. Every trial has specific criteria that spell out the characteristics a participant must have to join, such as a type and stage of cancer, a certain minimum cholesterol or blood pressure level, a specific age range (between 40 and 65, for example), or the absence of pregnancy or certain diseases. Participants may be required to undergo an extensive screening process involving blood tests and other medical procedures.

Finding a Trial

Sometimes a person’s doctor recommends participation in a clinical trial. This recommendation is particularly common for people who have cancer.

Trial recruitment ads run routinely in most major newspapers and on many local radio stations. Some local newspapers and newsletters now publish dedicated weekly sections listing clinical trials. Many communities have one or more research centers that consumers can call directly to get information or to get on a mailing list. Almost all clinical trials are listed at www.clinicaltrials.gov , a web site sponsored by the National Institutes of Health. Some web sites help match people to specific trials. For some top-rated organizations and web sites offering useful information about clinical trials, refer to Appendix IV (see ).

In the Trial

Some people find it tedious to participate in a trial, especially if it lasts many months or requires frequent visits to the research site or frequent blood tests. Some trial protocols require participants to regularly telephone the trial nurse to report symptoms or to keep a medical diary at home as a condition of remaining in the trial.

Some trials are delayed, canceled by the sponsoring organization, or even stopped early once underway because certain participants do not fare well while taking or receiving the experimental treatment. Delays or cancellations can be hugely disappointing to people whom the treatment brings relief. Also, after a clinical trial has ended, participants may no longer have access to an experimental treatment that was providing a real benefit.

Risks and Benefits

Deciding whether to participate in a clinical trial is an important and complicated decision. Both risks and benefits must be carefully considered.

Risks

First, participants should be aware that they are not guaranteed to receive the new treatment and may instead receive a placebo or older treatment.

A trial drug may have side effects and cause bad reactions ranging from headaches and sleeplessness to breathing difficulties or, on very rare occasions, even death. Although the researchers try to warn participants of all known side effects, unanticipated problems may develop.

The experimental treatment might not work as well as intended, possibly not even as well as standard treatment.

Benefits

There are also some very real benefits to clinical trial participation. If a treatment works as expected, participants could have a better outcome than with other treatments normally available to them. In some instances, participants have even been cured.

Volunteers typically receive excellent care in a manner that might otherwise cost thousands of dollars. Because participants are so well monitored, they tend to learn a great deal about their overall health and any underlying medical conditions. Sometimes there is an opportunity to build camaraderie with other participants, which may be particularly welcome by people who have rare or uncommon diseases. At a minimum, clinical trial participants can be sure that they are helping to advance medical science and public health.

Problems and Safeguards

In a very small fraction of situations, investigators in charge of clinical trials have acted unethically. One particularly shameful example is known as the Tuskegee experiments. Conducted around Tuskegee, Alabama, from 1932 to 1972, this study enrolled about 400 poor, mostly illiterate, African-American sharecroppers who had syphilis. These participants were not told that they had syphilis, and despite the widespread availability of the effective treatment penicillin, the Tuskegee investigators withheld penicillin and information about penicillin purely to continue to study how the disease progressed. Participants were also prevented from accessing syphilis treatment programs that were available to other people in the area. As a result of this horrendous breach of ethics and trust, several safeguards were put in place. Included in these safeguards are the establishment of Institutional Review Boards and the concept of informed consent.

Institutional Review Boards are specific committees in medical institutions that review proposed clinical trials involving humans. The purpose of these committees is to ensure that trials are conducted in an ethical manner and to avoid any unreasonable risks associated with the trial design. Only trials that have been approved by Institutional Review Boards are allowed to proceed.

Informed consent means that a person is given all the information needed to make an educated and informed decision as to whether to participate in a clinical trial. Information should describe all aspects of the trial, from its purpose to a statement about who pays for medical care to treat any research-related injuries. Informed consent documents tend to be lengthy (in some cases, dozens of pages long), technical, and hard to read. However, it is essential that participants read the documents carefully.

Participants should take the informed consent documents home, read them over several times, and discuss them with their personal doctor and family members. The doctor can help clarify some of the participation risks. Family members and friends particularly need to be involved if they will be providing transportation to the research center. After reviewing the informed consent documents carefully, participants should return to the investigator and trial coordinator and ask any further questions.

The protection of the safety and rights of clinical trial participants is a task shared by several government agencies as well as the Institutional Review Boards. However, to a large extent, participants—with the help of their doctor, family, and friends—must play an active part in their own protection. The Clinical Trial Participant’s Bill of Rights can help people understand how to protect their rights during participation.

Clinical trial participants can always quit a trial if it proves to be uncomfortable or too inconvenient. In addition, a vigilant investigator and trial coordinator will insist that participants drop out if there are changes in their health—such as an allergic or strongly negative reaction to the trial intervention—that make the trial too risky for them to continue. Investigators may also stop a trial if participants in one of the groups seem to be having very positive or very negative outcomes compared with participants in the other group. For instance, if the trial intervention is very effective, the trial may be stopped so that all participants may receive the intervention and benefit. If the trial intervention is ineffective or harmful, the trial may be stopped so that no more of the participants are harmed.

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