If Biomedical Science Is To Advance, Clinical Trials Researchers Need To Work With Human Subjects. Here's What You Need To Know About Participating In A Trial.

Choosing to participate in a medical research study is an important and very personal decision. By participating, you can make a tremendous contribution to your own health or the health of others. But you should be clear about what you're getting into - the benefits and the risks - before you agree to anything.

What Is A Clinical Trial?

A clinical trial is a scientific study. It tests how a new medicine, vaccine, medical device or treatment works in people, and it is one of the final stages of a long and careful research process. Human testing is allowed only after results from laboratory and animal studies show that the treatment under investigation is safe and likely to be effective. But clinical trials are not risk-free.

The basic steps:

1. A drug sponsor, usually a pharmaceutical company, has a new medicine or treatment thought to be medically useful and profitable.
2. Scientists analyze the drug's properties in the laboratory.
3. If those studies in the lab prove promising, researchers then study its pharmacologic and toxic effects in laboratory animals.
4. If these studies also show promise, the company will apply to the Food and Drug Administration (FDA) to begin human testing.
5. If the FDA allows it, the drug will be tested first in a small number of healthy human volunteers (about 20-80). Called Phase I clinical trials, these tests assess the most common side effects and determine safe dosage levels. They also let researchers know what happens to a drug in the human body - how it is metabolized, how much of it gets into the blood and various organs, how long it stays in the body (half-life), and how the body gets rid of the drug and its effects.
6. If Phase I studies don't reveal any major problems, the drug is then given to a larger number of people (about 100-300) - this time, to patients with the condition the drug is meant to treat. These studies, Phase II clinical trials, further evaluate the safety of the drug and determine whether it has a favorable effect on a specific condition or disease.
7. Phase III clinical trials involve a still larger number of volunteers (about 1,000-3,000). It confirms the effectiveness of the drug or treatment, compares it to commonly used treatments, and monitors side effects.
8. Once the FDA licenses the drugs or treatments that are safe and effective, Phase IV clinical trials continue to evaluate their effects in various populations.

Who Can Participate?

Clinical trials are usually for people with a specific disease or risk of disease, although healthy volunteers sometimes are needed. Customarily, health researchers have used mostly male adult volunteers. But pressure is growing for change.

Women have been left out of medical research studies for two main reasons: (1) researchers didn't think there were important differences in how diseases affected the sexes and (2) including women of childbearing age added increased complexity (and legal liability). Consequently, women of childbearing age were systematically excluded. But that practice is no longer legal. Both the National Institutes of Health (NIH) and the FDA have policies that forbid it.

It's clearer now that there are indeed meaningful differences in how some diseases and treatments affect women as opposed to men. Recently, the Society for Women's Health Research launched a campaign to encourage women to become "health heroes" by participating in medical research (www.womancando.org). They are also working to educate researchers, policymakers and clinicians about the importance of including women in clinical trials.

Plus the FDA now encourages drug sponsors to develop pediatric information through clinical trials and to establish specific dosages for children and elderly patients. Also, an FDA representative recently urged an increase in minority participation in clinical trials for the sake of meeting "the needs of the entire nation."

The Benefits of Participating in Research

• Without clinical trials, medical progress would be severely limited, perhaps even paralyzed. Clinical trials contribute to the existing knowledge about treating or preventing disease. If a treatment proves effective in a study, it may become a new standard treatment for many.
• Research in some areas, such as psoriasis, depends heavily on participation by human volunteers because there are no animal models for the disease or condition. The cooperation and willingness of people to participate is essential to progress.
• Study volunteers may be helped personally by the treatments they receive in clinical trials. In the past, clinical trials were sometimes seen as a last resort for people. Today, however, patients often choose to receive their first treatment in a clinical trial. This is especially true for patients with common cancers.

The Risks

• New treatments under study are not always better than, or even as good as, the standard method of care. They may have side effects that doctors do not expect or that are worse than standard treatment.
• Even if a treatment is proven effective for most people, it may not work for you.
• Volunteering for a clinical trial does not guarantee you will receive the drug or treatment under study. In a controlled trial, patients in one group receive the actual drug while those in the "control" group may get no treatment at all, a placebo (an inactive substance), a drug known to be effective, or a different dose of the drug under study. Patients are usually assigned to these groups randomly.
• Health insurance and managed care providers do not always cover all the costs of participating in a study. What they cover varies by plan and by study. You should determine in advance what will be covered by insurance and what might be reimbursed or paid by the group conducting the study.

How Can I Minimize Risks?

The federal government has strict guidelines and safeguards to protect people in clinical trials. Every trial must be approved and monitored by an Institutional Review Board (IRB), an independent committee of experts and lay people. The IRB makes sure the risks are as low as possible, that they're worth any potential benefits, and that the rights of study participants are protected.

IRBs are not perfect, however. They have come under increased scrutiny after several lapses in patient protection made news recently, most notably, the case of a young patient's death from a university gene therapy experiment.

With greater emphasis now being paid to patient protection, the IRB process is likely to improve over time. In the meantime, if you decide to participate in a clinical trial, pay close attention to the "informed consent" form. It details the nature of the study, the risks, and what may happen to a patient in the study. It also tells patients that they have a right to leave the study at any time. Federal law requires you to sign this form before you participate.

In addition, take the advice of Sharon Lee, a physician from Kansas City who wrote recently about the need to better balance research goals and patient care. "I believe each patient who becomes a clinical research subject ought to have an independent primary care physician providing medical care in the patient's interest apart from the research clinician who oversees his or her participation as a subject in medical experiments," Dr. Lee said in the Journal of the American Medical Association. Acknowledging the inherent conflicts of interest is not meant as a criticism . . . but may serve to increase the probability that the emphasis for each patient will be on medical care rather than on medical science."

What To Ask Before You Join A Clinical Trial

• What is the purpose of the study, and who is sponsoring it?
• What are the risks and benefits of participating?
• What medical procedures are involved?
• What are the possible immediate and long-term side effects?
• Will I be able to take my regular medications during the trial?
• Will the study researchers work with my doctor while I am in the study?
• How long will the study last, and how much of my time will it take?
• What are the costs, and will my insurance company cover?
• What do I do if I want to stop participating in the study after it has begun?