Clinical trials: What do they offer the volunteer?

Reprinted by permission from "New Medical Therapies," a CenterWatch newsletter designed to educate patients about particpating in ongoing clinical trials.

During the past 15 years, there has been a dramatic increase in the clinical testing of experimental drugs. In 1998, pharmaceutical and biotechnology companies [spent] more than $25 billion in the research and development of new drugs-ten times the amount spent 15 years ago. There are now more than 6,000 investigational drugs being developed worldwide. As a result, the clinical testing of experimental drugs is becoming part of the medical mainstream.

That can have important ramifications for you.

It used to be that clinical trials were conducted by a relatively small number of doctors, most of whom were faculty at academic medical centers. Today, there are more than 30,000 physicians involved in conducting clinical trials, the majority of whom practice in community settings. Research centers are also now using advertisements on television, radio and the Internet to recruit volunteers. All told, more than two million patients will volunteer for clinical trials this year.

In essence, more and more people today-and particularly those with chronic or life-threatening illnesses-view participating in a clinical trial as a healthcare option to be explored. One of the purposes of New Medical Therapies is to provide its readers with information about therapies in clinical trials and how to access those trials, and educational information about the process.

Why volunteer?
Volunteers cite a number of reasons for participating in clinical trials. There are some who volunteer purely for altruistic reasons: They want to contribute to medical research designed to bring improved medical therapies to the public. There are some who participate for financial reasons: They may lack health insurance and thus may volunteer in order to gain access to general medical care. And finally, those with chronic and life-threatening illnesses may seek out clinical trials today in order to gain early access to promising new therapies. In many instances, they will view a clinical trial as their best hope for a relief or a cure.

The notion of volunteering for a clinical trial, however, is likely to stir up a welter of confusing thoughts and emotions. How risky is it? Are you volunteering to be a human guinea pig? Who looks after the patients' rights? The patient's safety? Will you be treated with the experimental drug? Or a placebo? And if the experimental drug helps treat a chronic or life-threatening ailment, will you be able to get the drug after the trial ends?

If you are considering volunteering for a trial, it is essential that you become informed about the process. Volunteers need to weigh the risks versus the potential benefits.

"A clinical trial is not a known treatment. It's an experiment," says bioethicist Mildred Chos, assistant professor at the University of Pennsylvania Center for Bioethics. "There are no guarantees, only educated guesses. To a certain extent, you're flipping a coin. No one knows how the coin is going to fall. Not even the doctor."

Here is some of the critical information that every patient should know before getting involved in a clinical trial.

Who sponsors clinical trials?
The vast majority of clinical trials of drugs and medical devices are sponsored by pharmaceutical, biotechnology and medical device companies. Federal health agencies and research foundations also regularly sponsor clinical trials. In some instances, the trials will involve experimental drugs not yet approved for general marketing by the Food and Drug Administration (FDA). In other instances, the trials will be designed to provide an improved understanding of drugs that have already been approved by the FDA. A volunteer should know the sponsor of the trial and the status of the drug: Is it an investigational therapy or one already on the market?

Who pays for your medical care?
In most instances, the sponsor of the trial will pay for all research-related costs. Often, the sponsor will also pay for a volunteer's travel costs and pay a small stipend as well. Federal regulations prohibit researchers from offering a stipend in an amount that would be considered "coercive." Volunteers may also inquire about reimbursement for any child-care costs.

A volunteer's medical insurance may pay for some routine tests and procedures. These financial details should be spelled out in the Informed Consent document that every volunteer must sign. A volunteer in a trial should not be expected to pay for any trial-related care.*

Who protects your rights?
All clinical trials in the United States must be conducted with the approval of an Institutional Review Board (IRB). An IRB, which must have a minimum of five members, serves as the patient's advocate. Before a study begins, an IRB reviews the protocol to determine if it has a sound scientific premise and that risks to volunteers are minimized. The IRB will also review the Informed Consent document to ensure that it accurately informs the volunteer of the nature of the study.

Once a study is under way, the IRB must approve of any changes in the protocol. The principal investigator must also inform the IRB of all serious or anticipated side effects experienced by patients.

What is informed consent?
This form provides the volunteer with information about the anticipated effects of the drug and describes study procedures in lay terms. Before signing this form, you should ask questions about the study, and agree to participate only if you are satisfied with the answers. By signing the form, you are assuring the IRB and the FDA that your participation in the study is voluntary, and that you have been informed of the risks involved in the study. You should understand that you have other treatment options. You should also understand that you have the right to leave the study at any time.

What are the risks?
The clinical testing process is designed to minimize risks to human volunteers. At the same time, it is important to remember that clinical trials of investigational drugs are experiments. Does the drug work? What is the full range of side effects? A trial is designed to answer these questions. You can gain a better gauge of the relative risks of participating in a trial by understanding the testing process.

Before a pharmaceutical company can begin testing an experimental drug in humans, it must conduct extensive laboratory and animal tests. The preclinical testing provides information about the drug's biological activity, whether it is toxic to human cells at a certain dosage, and how well it is tolerated by animals. By some estimates, fewer than 1% of drugs that enter preclinical testing are ever tested in humans.

The clinical testing of a new drug is done in three phases. Each successive phase involves a larger number of people. Phase I studies are primarily concerned with assessing a drug's safety. This initial testing usually involves 20 to 100 healthy people, who are paid for their participation. The phase I study is designed to determine what happens to the drug in the body-how it is absorbed, metabolized and excreted. About 70% of investigational drugs pass this initial phase of testing.

Next, an investigational drug is tested for safety and effectiveness in a small number of patients with the targeted disease. Phase II studies may last up to two years and involve several hundred patients. Only about 50% of all drugs that enter phase II trials successfully complete this testing stage. The investigational drugs may fail this stage either because they do not appear to be effective in treating the disease, or because side effects are found to be too severe.

After a successful phase II study, the drug manufacturer has preliminary evidence that its new drug can provide a therapeutic benefit. The drug company also has a fairly good understanding of the drug's short-term side effects and possible adverse reactions. To build further on this knowledge, a pharmaceutical company must conduct phase III studies involving several hundred to several thousand patients across the country. About 80% of all drugs that enter phase III successfully complete this stage. After phase III trials have been successfully completed, pharmaceutical companies will seek FDA approval to market the drug.

As a volunteer seeking treatment for an ailment, you will be recruited primarily for phase II, phase III and post-approval trials. Volunteers assume the greatest risk-and this risk is primarily in the form of unexpected side effects-in phase II trials. Before you agree to participate in any trial, you need to decide whether the risks are acceptable to you.

Will you get access to the investigational drug?
If you are volunteering in order to gain early access to a new treatment, it is imperative that you understand that you may not be treated with the experimental drug. In most studies, volunteers are randomized to one of two groups. The patient is either given the study medication or a standard treatment (or a placebo that has no biological activity). In such instances, a volunteer has only a 50% chance of gaining access to the experimental therapy. Furthermore, in most instances, after the study has ended, volunteers are not able to gain continued access to the study drug. Your access to a promising new therapy may be limited to the time period specified by the study protocol.

What are other drawbacks?
Volunteers in clinical trials generally must stop taking any other medications that they may have been taking for the targeted disease. They usually must go to the physician's office for several regularly scheduled visits. Volunteers may have to wear monitoring equipment and usually will have to have their blood sampled at regular intervals. You should expect that volunteering for a clinical trial will require an investment of time, and will require that your reactions to the study drug be closely monitored and analyzed.

There may be other factors and issues that you will want to consider before volunteering for a clinical trial. It is important that you discuss this option with your physician or medical caregiver. You should agree to participate in a clinical study only if you believe that your questions about the study and its risks have been fully answered.

"Patients must take responsibility to make sure they are fully informed and have all their questions answered," says Marilyn North Arnold, director of clinical trials research for Patient-Centered Healthcare in Avon, Conn. "No patient should ever leave a clinic where they are considering getting involved with a research study with any doubt or any question lingering on his or her mind."

Copyright 1998 by CenterWatch, a Boston-based publishing company. For subscription information, call 617/247-2327, or visit web site www.centerwatch.com.

* Editor’s note: A "cost-recovery program" such as that currently in place for Ampligen is not a clinical trial.

Clinical trial safety questioned; regulations out of date
People in medical studies are inadequately protected from risks, with hazards often poorly explained and scientists often snared in conflicts of interests, according to a panel of bioethics experts at the University of Pennsylvania.

In an article in the Dec. 9, 1998, issue of the Journal of the American Medical Association, members of a panel from the Center for Bioethics at the University of Pennsylvania note that regulations put in place to protect patients have been unchanged for 17 years, despite many changes in the nature of clinical research. Co-author and Center for Bioethics Director Arthur Caplan said the current system is too bureaucratic, too expensive and lacks sufficient protection for the patients.

Also, the regulations apply only to government-funded research, not to privately funded research. That’s a problem, Caplan said, as medical research centers increasingly get funding from drug companies and other for-profit entities rather than the federal government. Caplan said the consent forms that are used have become focused on reducing legal liability for researchers and institutions, rather than on helping subjects make informed choices. The forms are too long and too technical and fail to give the subjects an idea of what really happens in research.