Merck Manual

Please confirm that you are not located inside the Russian Federation

Loading

What Participants Need to Know About Clinical Trials

By

Oren Traub

, MD, PhD, Pacific Medical Centers

Last full review/revision Sep 2018| Content last modified Sep 2018
Click here for the Professional Version
NOTE: This is the Consumer Version. DOCTORS: Click here for the Professional Version
Click here for the Professional Version
Topic Resources

People expect doctors to use treatments that work well and to stop using those that do not. However, it is often difficult for doctors and other scientists to tell which treatments work. Making this distinction is part of the science of medicine and usually involves studying the effects of treatments in clinical trials.

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.

Key Questions to Ask Before Participating in a Clinical Trial

  • What is the main purpose of this trial?

  • Does the trial involve a placebo or a treatment that is already on the market?

  • How will the treatment be given to me?

  • How long is the trial going to last?

  • What will I be asked to do as a participant?

  • What has already been learned about the trial treatment and have any trial results been published?

  • Do I have to pay for any part of the trial? Will my insurance cover these costs?

  • Is there any reimbursement for travel costs, parking, or child care?

  • Will I be able to see my own doctor?

  • If the treatment works for me, can I keep using it after the trial has ended?

  • Can anyone find out whether I am participating in a clinical trial?

  • Will I receive any follow-up care after the trial has ended?

  • What will happen to my medical care if I stop participating in the trial?

  • Do the trial doctor and investigator have any financial or special interest in the trial?

  • What are the credentials and research experience of the trial doctor and trial staff?

Adapted from The Center for Information and Study on Clinical Research Participation, www.ciscrp.org/.

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 (NIH) or by a pharmaceutical, biotechnologic, or medical device company. Investigators follow a detailed protocol (list of instructions) 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 in The Science of Medicine.

All interventions must be approved by the U.S. Food and Drug Administration (FDA) before they can be prescribed or used (see FDA: The Drug Development Process). 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. An optional fourth phase is often done after an intervention is approved.

Phase I trials assess the safety of an intervention but not its usefulness in treating a disease. 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. These participants receive monetary compensation, with the amount dependent on the time commitment and the nature of the drug or procedure being tested.

Phase II trials are conducted if the intervention seems safe in a phase I trial. 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.

Phase III trials are conducted if safety is still satisfactory in phase II and the intervention seems effective. 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 10 years from when a drug is initially discovered until it is approved for market. About seven years of this time is for the clinical testing process. Many drugs, medical devices, and diagnostic tools never complete all three phases. Others do complete the three phases but are not approved for use because they fail to be effective or safe or both.

Phase IV trials are conducted to evaluate interventions that have already been approved for use. One type of phase IV trial is done to compare two or more approved interventions or to test an approved intervention on a disease for which it is not approved. When an intervention is tested for a new disease, three phases are not needed, but the clinical trial design is similar.

Postmarketing surveillance is another type of phase IV trial, which is done after the drug or device has been approved and is in widespread use in the general public. This study uses information from medical health records and doctors' reports to identify any side effects that were not detected in the first three phases of clinical trials. Postmarketing surveillance is particularly important in detecting side effects that are uncommon (and thus might not show up even in a phase III trial) or that occur mainly in a unique group of people, such as pregnant women or people of a certain ethnic origin who might not have been part of the original trials. If new side effects are identified and are serious, use of the drug or device might be restricted, or the drug or device might even be removed from the market.

The Clinical Trial 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 or to receive money. 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 clinical 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 NIH. Some web sites help match people to specific trials. For example, the NIH has an internet-based registry called Research Match, which people can use to connect with researchers seeking participants for their studies. CenterWatch is another service that contains thousands of trials that are currently enrolling people.

While in the clinical 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 to 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 of Participation in Clinical Trials

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

Risks of participation in clinical trials

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 of participation in clinical trials

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 Clinical Trials

In a very small fraction of situations, investigators in charge of clinical trials and studies 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 (IRBs) are specific committees in each medical institution that participate in clinical trials. Committee members must include at least one non-scientific member and at least one member who is not affiliated with the institution at which the research is being done. IRBs review all 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 the IRB of an institution are allowed to proceed in that institution. Each institution's IRB may evaluate and approve studies independently from other IRBs. Alternatively, when many different institutions participate in a study, the FDA permits use of a Central IRB that performs the review for that study. Using a Central IRB can eliminate a lot of duplicated effort by separate committees and also ensure a consistent set of protections and requirements at all the study centers. The Central IRB for a study may be the individual IRB at one of the study sites or a private, independent IRB. Central IRBs must still follow all local requirements at each participating site.

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.

Elements of Informed Consent Documents

  • Major Elements

    • A statement explaining the trial’s purpose, the procedures to be followed, the duration of participation, and any investigational treatments or procedures

    • A description of foreseeable risks and discomforts to participants

    • A description of benefits that the participant can reasonably expect

    • A disclosure of any alternative treatments or procedures that might be advantageous to participants

    • A statement about how participant confidentiality is maintained

    • An explanation of compensation and whether medical treatments are available if injury occurs

    • A list of contacts to answer trial-related questions and to help with research-related injuries

    • A statement that participation is voluntary and that there is no penalty and no loss of benefits for refusing to participate

  • Other Elements When Appropriate

    • A statement that there may be unforeseeable risks to the participant, embryo, or fetus—if the participant is or may become pregnant

    • A list of circumstances under which the investigator may terminate a participant’s enrollment

    • A description of additional costs to the participant

    • An explanation of the consequences and procedures if a participant decides to withdraw

    • A statement that participants will be informed of significant new findings that might affect their willingness to participate

    • The approximate number of participants enrolled in the trial

Adapted from The Food and Drug Administration, Code of Federal Regulations, Title 21, Section 50.25 (www.fda.gov).

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 IRBs. 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.

The Clinical Trial Participant's Bill of Rights

Any participant who gives consent to participate in a clinical trial or who is asked to give consent on behalf of another has the following rights:

  • To be told the purpose of the clinical trial

  • To be told about all the risks, side effects, or discomforts that might be reasonably expected

  • To be told of any benefits that can be reasonably expected

  • To be told what will happen during the trial and whether any procedures, drugs, or devices are different from those that are used as standard medical treatment

  • To be told about available options and how such options may be better or worse than what is being studied in the clinical trial

  • To be allowed to ask any questions about the trial before giving consent and at any time during the course of the trial

  • To be allowed ample time, without pressure, to decide whether to consent to participate

  • To refuse to participate, for any reason, before and after the trial has started

  • To receive a signed and dated copy of the Informed Consent form

  • To be told of any medical treatments available if complications occur during the trial

Adapted from The Center for Information and Study on Clinical Research Participation, www.ciscrp.org.

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.

More Information

NOTE: This is the Consumer Version. DOCTORS: Click here for the Professional Version
Click here for the Professional Version
Others also read

Also of Interest

Videos

View All
Positron Emission Tomography-Computed Tomography ...
Video
Positron Emission Tomography-Computed Tomography ...
A PET-CT scanner merges both PET and CT capabilities into one machine to identify abnormal...
How to Protect Your Health While Traveling Abroad
Video
How to Protect Your Health While Traveling Abroad

SOCIAL MEDIA

TOP