Understanding Clinical Trials


A clinical trial usually offers you the best option for treatment, but the concept of clinical trials can seem overwhelming and confusing, especially when you are already coping with a diagnosis of cancer. Before you can decide whether to participate in a clinical trial, you should understand how clinical trials are carried out and know the meaning of the words used in describing clinical trials (Table 1).

Types of Cancer Clinical Trials

In general, clinical cancer research is conducted within five types of clinical trials; two types of trials — treatment trials and quality-of-life trials — are specifically related to individuals who have cancer. Three other types of trials — prevention, screening, and diagnosis — are often done among broader populations of individuals, many of whom do not have cancer. The discussion here is limited to treatment trials.

A treatment trial is done to evaluate whether a new treatment (drug, surgery, or radiation therapy) or new combination of treatments is better than the treatment currently considered to be the standard of care. Trastuzumab (Herceptin) has been effective for many women with breast cancer and imatinib (Gleevec) has been effective for many people with leukemia or gastrointestinal stromal tumors because of treatment trials carefully designed to evaluate these drugs. In addition, many women with breast cancer can now safely choose to have lumpectomy rather than mastectomy because clinical trial results showed that the two procedures have similar outcomes. These are just a few examples of the advances in cancer treatment as a result of clinical trials.

Focus on Biologic Therapies: A New Trend in Clinical Trials

Nearly half of the clinical trials conducted in the last several years have focused on biologic therapies. Some biologics work with your immune system while others act directly against the cancer cell. The purpose of biologic trials is to find the specific susceptibility of cancer cells to different agents. Biologic trials may examine the efficacy of multi-agent biologics with or without standard chemotherapy treatments.

Targeted therapy trials are one promising subset of biologics. Targeted cancer therapies are drugs or other substances that block the growth and spread of cancer by interfering with specific molecules involved in tumor growth and progression. By focusing on molecular and cellular changes that are specific to cancer, targeted cancer therapies trials may determine if this approach is more effective than other types of treatment, including chemotherapy and radiotherapy, and whether it is less harmful to normal cells.

Phases of Treatment Trials

Most cancer treatment clinical trials are done as part of the development of a new drug after the drug has been shown to destroy cancer cells in studies of animal models or cultured cancer cell lines (cancer cells that have been adapted to grow in the laboratory). The U.S. Food and Drug Administration (FDA) reviews the results of these preclinical trials and approves (or rejects) the use of the drug in studies in humans. Some cancer treatment clinical trials involve a drug that has already been approved by the FDA but for a type of cancer different from the one to be studied in the clinical trial.

Cancer treatment trials are designed in a specific order of steps, referred to as phases, with each trial providing the building blocks of knowledge for the next trial phase. This systematic approach allows researchers to ask and answer questions in a way that produces the most reliable information and that provides the best protection of trial participants. These clinical trials are classified as phase I, II or III (Table 2).

Phase I trials are the first studies in which a new drug (or other type of treatment) is evaluated in humans. The goal is to determine how the drug should be given (orally or intravenously, for example), how often the drug should be given and what dose is most effective at killing cancer cells while causing the fewest side effects. Often, the participants in a phase I trial have different types of cancer, and researchers are seeking to discover what type of cancer the drug works best against.

The goal of phase II trials is to determine how well a drug works and how safe it is in a greater number of patients. Phase II trials usually involve people who all have the same particular type of cancer.

The next step is a phase III trial, in which the new drug is compared with the current standard of care. Phase III trials are also done to evaluate other types of treatment, such as radiation and surgery, and combinations of treatments (either combinations of specific drugs or combinations of types of treatment, such as surgery followed by chemotherapy). Participants in a phase III trial are randomly assigned to receive either the experimental drug or treatment or the current standard treatment. Phase III trials often involve patients who are treated at many different cancer treatment facilities to determine the benefit of the treatment among a broad representation of patients. Patients are usually followed for several years after treatment so that long-term survival benefit and other outcomes (such as late side effects) can be determined. Most studies are blinded, which means that information is not given about which treatment group each study participant is in. Blinding helps prevent the results from being influenced by the expectations of the researchers or participants.

When the results of a phase III trial indicate that a new drug leads to better outcomes for patients and is safe (the side effects are minimal and/or manageable), a special committee reviews the results and recommends approval of the drug by the FDA.

Safety of Clinical Trials

Many individuals with cancer fear participating in a clinical trial because they think trials are not safe. However, several safeguards are built into a clinical trial to ensure the safety of all participants.

First, every clinical trial follows a set of rules called a protocol. The protocol defines the eligibility criteria, specifies the tests to be done and the procedures to be used, describes the medications and their doses and establishes the duration of the study. Before the study begins, a scientific review panel evaluates the protocol carefully to make sure the trial is based on sound science. An institutional review board (IRB) also evaluates the protocol to ensure that patients will be treated ethically and that the risks involved in the trial are reasonable compared with the possible benefits.

The second safeguard is the informed consent process, which protects participants throughout the duration of a clinical trial. This process requires that the research team explain all the details about the trial to you, including the purpose, tests and treatment involved, possible risks and benefits, so that you can make an informed decision about volunteering for the trial. Be sure to ask your physician or the research team to have someone describe the trial to you in your native language if that will help increase your understanding.

The third safeguard is safety monitoring throughout the duration of the trial. This monitoring is done by both the IRB and a special committee, a data safety and monitoring board. These two panels of experts ensure the safety of participants by reducing potential risks as much as possible. The data safety and monitoring board will stop a trial if safety concerns arise or if either the experimental treatment or the standard treatment is overwhelmingly better than the other.

What to Expect in a Clinical Trial

The research team will give each participant specific instructions about the trial, will evaluate each participant’s health at the beginning of the trial and monitor it carefully during the trial and will stay in touch with each participant after the trial ends. To have the greatest likelihood of benefit from the trial, participants should carefully follow the instructions and remain in contact with the research staff.

Clinical trials may be conducted in a hospital, university, doctor’s office or community clinic, depending on the intensity of the treatment and the need for monitoring side effects. Health insurance usually covers the costs of treatment in a clinical trial. (See Financial Help).

Evaluating a Clinical Trial’s Benefits vs. Its Risks

There is a risk that a new treatment may not be effective for you. You may experience serious, unpleasant and life-threatening side effects from the treatment. In addition, your protocol may require more time spent at the study site, a hospitalization, or complex dosage requirements.

On the other hand, clinical trials give you access to new treatments that are not widely available as well as cutting-edge medical care. By participating in medical research, you also help others with a similar disease to share new discoveries. You and your physician need to determine if, for you, the benefit of a clinical trial outweighs its risks.

Table 1. Definitions of Terms Used in Clinical Trials

Term Definition
Blinded A study design in which the participants do not know which treatment group they are in. A single-blind trial is one in which the participants do not know which treatment they are receiving, but the researchers do. A double-blind trial is one in which neither the participants nor the researchers know who is receiving the experimental drug or therapy and who is not.
Control group The participants who are assigned to receive the standard treatment that is being compared with one or more experimental treatments.
Eligibility criteria The guidelines defining the characteristics (age, sex, health status, type and stage of cancer, etc) of the people who can participate. Inclusion criteria are the characteristics needed to participate in the trial, and exclusion criteria are characteristics that disallow a person from participating. Eligibility criteria are designed to keep participants safe and to help provide reliable results.
Endpoint (primary and secondary) The primary endpoint is the main result or outcome that is being measured in the study. The primary endpoint may be the difference in survival between the treatment group and the control group, or it could be the length of time before disease recurred in the people in each group. In phase II trials, the primary endpoint may be how well cancer responds to the drug. A secondary endpoint is another result or outcome the researchers wish to measure. Primary and secondary endpoints are determined before the study begins.
P value A statistical measure of probability, or the likelihood that a difference in an outcome between two groups happened by chance. The lower the p value, the more likely that the difference in an outcome is due to the difference in treatment between the experimental and the control groups. The results of a clinical trial are usually considered statistically significant when the p value is 0.05 or less. A p value of 0.01 or 0.001 represents a result of even greater significance, which means that the experimental treatment is even more effective. (See also “statistical siginificance.”)
Placebo An inactive agent given in a control group, to simulate treatment with an active agent. Placebos are not used instead of treatment in cancer clinical trials. A placebo may be used with standard treatment in a control group when the experimental treatment involves the standard treatment plus a new drug.
Random assignment (randomization) The assignment of participants by chance to either the standard or experimental treatment group. By not allowing the researchers or the participants to choose the group, the participants in each group will be similar and the results can be compared objectively.
Relative risk A statistical term referring to the likelihood that an event (such as cancer recurrence, an adverse event or survival) will occur within a specific time in one group compared with another. For example, if the risk of recurrence is 3 times higher for one treatment group compared with the other, the relative risk is 3.
Standard treatment (or therapy) The drug or treatment that experts agree is the most accepted, widely used and appropriate therapy for a particular type and stage of cancer. The standard treatment is used as a baseline against which an experimental drug or treatment is compared in a phase III trial.
Statistical significance If the results of a clinical trial are said to be statistically significant, it means the results are more likely to have occurred from a difference in treatments (standard or experimental) than to have occurred by chance. A statistically significant difference between the results for two or more groups in a trial usually means that one treatment is much more effective. But several factors are involved with statistical significance, and a significant difference may not necessarily be meaningful in the clinical context.
Trial size (or sample) The number of participants in a clinical trial. This number greatly influences the statistical significance of a trial. For example, if the trial size is too small, the results may not be significant enough for the researchers to draw a valid conclusion. Before starting a clinical trial, researchers determine how many people must be enrolled in the trial in order to get a statistically significant result.


Table 2. Phases of Clinical Trials

Phase of Trial Typical No. of Patients Purpose
I 15-50
Find a safe dose

Decide how the new treatment should be given

Identify side effects

II Less than 100-150
Determine the effect of a new treatment on a specific type of cancer

Identify side effects

III 100s to thousands
Compare the new treatment (or new use of a treatment) with the current standard treatment

Monitor side effects

Additional Sources of Information


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