Clinical trials: Is one right for me?

If you are living with a serious or chronic (long-term) condition, you may be wondering if a clinical trial is an option worth considering. After all, participating in a clinical trial can place you in the care of some of the nation’s top physicians, and you may find a treatment that works. Naturally, you also are concerned about the risks involved. To help you decipher the jargon and make an informed decision, the following provides basic facts about clinical trials in a Q&A format and links to other sources that may help.

What is a clinical trial?
A clinical trial is a medical investigational study in which humans are observed and/or treated.

The National Institutes of Health (NIH) recognizes five (5) types of clinical trials:

• Treatment trials test new treatments, new combinations of drugs or new approaches to surgery or radiation therapy.

• Prevention trials look for better ways to prevent disease in people who have never had the disease or to prevent a disease from returning. These approaches may include medicines, vitamins, vaccines, minerals or lifestyle changes.

• Diagnostic trials are conducted to find better tests or procedures for diagnosing a particular disease or condition.

• Screening trials test the best way to detect certain diseases or health conditions.

• Quality of Life trials (or Supportive Care trials) explore ways to improve comfort and the quality of life for individuals with a chronic illness.

Treatment trials are generally conducted in phases. The other types of clinical trials may not have phases. This is what happens during each phase:

Phase I – This is the first time humans receive the new drug or other treatment under investigation. Phase I occurs after the basic science, laboratory and animal studies indicate that an approach, medicine, etc. may be safe and effective for treatment of a specific condition. The NIH defines a Phase I study as a study in which “researchers evaluate what dose is safe, how a new agent should be given (by mouth, injected into a vein, or injected into the muscle), and how often. Researchers watch closely for any harmful side effects.”

The number of people who participate in a Phase I study is small, generally 20 to 80 volunteers. A treatment may be recommended for Phase II studies after researchers determine the highest dose that can be taken with acceptable side effects.

Phase II – During this phase, the safety and effectiveness are studied in volunteers who have the condition for which the treatment is being considered. Several hundred volunteers may be enrolled in a number of Phase II studies. Volunteers are selected via the criteria outlined by the researchers in the study protocol (study plan). If Phase II trials are satisfactorily completed, Phase III studies are conducted.

Phase III – In Phase III, the investigational treatment is compared to a standard therapy currently used to treat the condition and the overall benefits and risks of the treatment under investigation are evaluated. The data gathered from Phase III trials provides a better understanding of the treatment’s effectiveness, benefits and potential side effects.

During a Phase III trial, volunteers are divided into two (2) groups:

1.       Control group – The volunteers in the control group do not receive the investigational treatment. They receive either a currently accepted treatment or a placebo.

2.       Study group - The volunteers in the study group receive the treatment under investigation.

Volunteers are randomly assigned to a control group or a study group. They do not get to choose which group they want to join and are not told which treatment they receive. Assigning volunteers by chance ensures that the groups will be similar and the treatments can be compared objectively.

Since the volunteers do not know if they are receiving the investigational treatment, standard treatment, or a placebo, they are said to be “blinded.” This ensures unbiased results. The researchers also may be “blinded,” (i.e., they do not know which treatment each participant receives). When both the volunteers and researchers are “blinded,” the study is termed “double-blinded.”

If you enter a Phase III study, you will likely be part of a “double-blinded,” randomized control trial (RCT). In a “double-blinded” RCT, volunteers are assigned by chance to each group. Both the volunteers and the researchers are “blinded.” Using chance to assign volunteers allows the treatments and results to be objectively compared. A “double-blinded” RCT is the ideal study for scientifically demonstrating the effect of a therapy. In fact, pharmaceutical firms often sponsor these types of studies to gather the data needed to submit a drug to the U.S. Food and Drug Administration (FDA) for approval.

A large number of volunteers are sought for Phase III clinical trials. Several hundred to several thousand volunteers may be enrolled in a Phase III trial. These trials are conducted over a period of years in hospitals, medical centers and private physicians’ offices across the United States. They also are conducted by large medical centers and government-supported organizations such as the NIH and the Veterans Administration.

Once Phase III testing is complete, a pharmaceutical company can submit a drug to the FDA. The FDA uses the data to help determine whether or not to approve the drug.

Phase IV – Phase IV trials are not always conducted. When they are, they usually take place after the treatment receives FDA approval and is available to the public. During a Phase IV trial, long-term safety and effectiveness, side effects that may not have been apparent during Phase III and optimal usage are evaluated. Hundreds to thousands of volunteers may participate in a Phase IV trial.

What happens to the data collected during a clinical trial?
Data from all types of clinical trials, not just treatment trials, is analyzed by the primary investigators who draw science-based conclusions. The data and conclusions are then documented in papers. These papers are usually referenced in a data bank, such as MedLine, the data retrieval system of the National Library of Medicine. Papers can be retrieved, usually for decades, by physicians, non-physician scientists and anyone else who is interested. 

Researchers also report their findings at medical meetings, to scientific journals and to various government agencies. Articles may be written that appear in scientific journals, such as the Journal of the American Academy of Dermatology. At the American Academy of Dermatology’s annual and summer meetings, researchers present their findings and allot time for fellow dermatologists to ask questions. The goal is to provide information that helps patients worldwide.  

Data collected about new drugs also is submitted to the U.S. Food and Drug Administration (FDA) as described above.

When a study is deemed well-designed and its results are scientifically and statistically valid, it may be referenced in future studies. It also is possible that future studies may seek to build upon or critically examine its results. Such a study becomes a building block in a constantly evolving information base.

Who is eligible to volunteer for a clinical trial?
Clinical trials have eligibility guidelines for volunteers. This ensures that the study’s questions can be effectively answered. The eligibility guidelines are published in a public notice. Eligibility criteria include age, gender and medical history. Within the eligibility guidelines, researchers write “inclusion criteria” and “exclusion criteria.” Inclusion criteria are factors that the researchers seek, such as having a certain medical condition. Exclusion criteria identify factors that preclude a volunteer from participating. For example, the study may exclude people who are already participating in another clinical trial. 

What are the major benefits and drawbacks of being in a clinical trial?
The primary benefits of participating in a clinical trial are:

• Gaining access to new treatment before it is widely available

• Possibility of being placed in the care of some of the nation’s top physicians

•  Helping contribute to medical research that may one day benefit many patients

• Many costs may be covered by a federal program or pharmaceutical sponsor

Drawbacks to participating in a clinical trial include the possibility of: 

• Unpleasant, serious or even life-threatening side effects

• Receiving a placebo or standard treatment rather than the investigational treatment (Volunteers agree to this risk when they consent to participate in the study.)

• Receiving treatment that is ineffective

• Assuming responsibility for many costs (Costs are not always covered by health insurance or a sponsor.)

• A greater time commitment since participation may require more of the volunteer’s time than a standard treatment due to trips to the study site, possible need for more frequent observation or treatment, hospital stays and other factors

If I participate in a clinical trial, will I have to be away from home?
This depends on a number of factors, including the study protocol, the severity of your illness, and where a trial is conducted. When patients are very ill or 24-hour monitoring is required, the trial may be conducted at one, or even a few, large medical centers and require the volunteers to remain at the center during the trial. Other trials may have many dispersed locations and only accept volunteers who can get from location to location. Most dermatologic illnesses do not require a hospital stay unless 24-hour monitoring is a condition of the trial.

How long does a clinical trial last?
Duration varies and depends on the time required to test the study hypothesis adequately. A clinical trial can last a few days, several weeks or years. In a randomized control trial, a volunteer may be asked to return for follow-up testing for several weeks or months after the treatment phase is over. The volunteer’s time commitment will be specified in the public notice for the clinical trial.

Is the volunteer liable for any of the costs associated with a clinical trial?
This varies from trial to trial. Health insurance may not pay for some, or all, of the costs of treatment received during a clinical trial since some insurance plans regard clinical trials as "investigational" treatment. Investigational treatments are typically not a covered cost. Trials underwritten by a pharmaceutical firm usually pay some, but not all, costs of treatment. In such a clinical trial, the volunteer may be liable for some expenses, such as those for tests. Before entering a clinical trial, a prospective volunteer should learn what costs will be covered by the sponsor and health insurance as well as what costs will become the volunteer’s responsibility.

How can I find out what will be required during a clinical trial?
This, too, is published in the public notice. Each and every clinical trial must adhere to federal and institutional rules and regulations. Federal regulations, and the rules of each institution involved in a clinical trial, require that:

1.       Every trial must be approved by an Institutional Review Board (IRB) to assure that volunteer rights and safety are adequately protected.

2.       A volunteer must give “informed consent.” Informed consent means that the volunteer agrees to participate in the trial under conditions explained by the investigators. However, the volunteer is not legally bound to remain in the trial, and may leave at any time without penalty. It is hoped that volunteers will remain in the trial so that study results are not skewed by dropouts.

Informed consent requires the study’s researchers to thoroughly inform volunteers about:

• The study’s plan

• Treatment to be given during the trial

• Tests that will be carried out

• Follow-up procedures after the trial

3.       If the study is blinded and placebo-controlled, the volunteer must be told that he or she may receive a placebo or the standard treatment rather than the investigational treatment.

Once a potential volunteer knows what will happen during a clinical trial, the person is strongly urged to carefully think about whether or not to participate and to discuss the study with family and physicians before making a final decision.

How do I find clinical trials?
To find clinical trials conducted by an authoritative sponsor, you should:

• Talk with your dermatologist about participating in a clinical trial. Ask if a clinical trial is a treatment option you should consider, and if so, which one(s) would be best for you.

• Contact large medical centers and pharmaceutical firms regarding any trials they may be conducting or planning in the area of your interest.

• Search the Internet. Visit the web sites of medical centers, pharmaceutical companies, the Food and Drug Administration (FDA) and government-sponsored research centers, such as the National Institutes of Health (NIH). Information on clinical trials sponsored or approved by the NIH and FDA is available at ClinicalTrials.gov.
   

Links
The following links take you to other web sites that provide information about clinical trials and offer resources to help you locate clinical trials seeking participants:

“About ClinicalTrials.gov.” National Institutes of Health.

“Cancer Facts.” Clinical Trials: Questions and Answers.” National Cancer Institute.

Delaney P. “Understanding Clinical Trials from the Patient’s Perspective.” U.S. Food and Drug Administration. October 1, 1997.