Health & Fitness
Treatment by trial - Some patients find rewards outweigh the risks of participating in a clinical study

When Deborah McDaris of Brighton was diagnosed with Early Stage I cancer in 1999, she and her husband, Mark, sought cutting-edge treatments to rid her body of the disease.

McDaris decided to participate in two clinical trials taking place at William Beaumont Hospital in Royal Oak. One trial researched how the condition of the main lymph node in an area of cancer -- known as a sentinel node -- reflects cancer spread and recurrence. The other study involved chemotherapy advancements for breast cancer.

"I was a pharmaceutical sales representative for eight years, and so I was familiar with what a clinical trial was, and how important they are," says McDaris, now 39. "People seem to be so nervous about participating in a clinical trial, but they should remember that today's standard treatment was once a new treatment, too. All the reading material I had seen recommended going to a hospital that does clinical trials, because that is how you gain access to the best doctors and truly cutting-edge therapies."

Clinical trials, such as the ones McDaris participated in, also are called clinical research or research studies. About 40,000 clinical trials in the United States are testing new medications, comparing different treatments for the same disease or condition and seeking factors that may influence development of chronic illness or disease.

Participating in a clinical trial has some potential drawbacks, including uncertainty about what drug or treatment you're receiving. You have little or no choice about the kind of treatment or amount of a drug that you receive, and you may experience uncomfortable or even dangerous side effects of these untried compounds.

However, clinical trials can play a pivotal role in proving that new medications work and influencing how quickly they become available to treat patients in the general public. For example, the Food and Drug Administration recently approved a new drug for the treatment of a form of leukemia.

The drug, Gleevec (also called STI-571), was shown to return white blood cell counts to normal in approximately 90 percent of patients with chronic myeloidgenous leukemia, and had only mild side effects. Scientists say Gleevec could be the first drug in a brand-new class of drugs designed to treat many types of cancer in a new way.

Prime testing ground

If you are interested in participating in a trial, southeastern Michigan is a good place to be. Patients in our area have access to many major hospitals and health systems that conduct clinical research and thus gain access to brand-new treatments that are not available to the general public.

Some trials are small, with only a dozen or so participants. Others can require tens of thousands of people and continue for as long as a decade. But while enrollment in clinical trials is slowly increasing, physicians and researchers say many people still harbor misconceptions about what clinical trials are.

"People still sometimes think they are signing up to be experimented upon, even using the term 'guinea pig,'" says Dr. Steven Borzak, associate division head and clinical researcher for the Henry Ford Heart and Vascular Institute in Detroit. "But what people need to realize is that science has advanced tremendously in the last few decades, and the standard by which we evaluate new treatments has changed, too."

Before a trial can take place, a committee called an institutional review board must approve the research. Every research facility or hospital has one such a board. Comprised of scientists, doctors, nurses, social workers, medical ethicists, clergy and sometimes members of the general public who have no personal interest in the results, the board is mandated by federal regulations. Its responsibility is to protect participants by making sure the treatment's risks are low, and each patient has been apprised of the reasons, procedures, risks and alternatives of the trial.

"The doctors and nurses gave me a lot of information," says William Bridges of Detroit, a 57-year-old who had a stroke in 1999. He was approached to participate in a Wayne State University/Detroit Medical Center study for the prevention of second strokes. He currently takes medication as part of the study.

"I have learned a lot, and I think I am getting great care. My medicine is free, and my nurses are great," Bridges says. "And I also like that I'm helping other people."

Physicians say they are often surprised at participants' altruistic motives.

"I give these patients so much credit for pulling outside of themselves and their situation, and agreeing to be part of a trial in order to potentially help other people somewhere down the line," says nurse Veronica Decker, director of the William Beaumont Cancer Clinical Trials Office, which is overseeing 100 clinical trials for the treatment or prevention of cancer. "For example, if those 13,500 women hadn't participated in the STAR (Study of Tamoxifen And Raloxifene) trial, we wouldn't know that there are drugs that can help prevent breast cancer. That's pretty phenomenal."

On the cutting edge

Research can be incredibly exciting, says Dr. Jim Bengtson, medical director for research at the Michigan Heart & Vascular Institute in Ypsilanti, part of the St. Joseph Mercy medical system.

One of Bengtson's trials sounds like something out of Star Trek. In his photoangioplasty trial, patients take a drug that works with the assistance of a special light. When the drug is in the bloodstream, a light source within the clogged artery activates the drug, which then "chews up" plaque that is blocking the blood flow and clears the vessels.

"In my view, it's one of the most exciting trials we are doing," Bengtson says. "It's really cutting-edge, and it may very well be the next great, effective thing."

It's also an example of the pros and cons of research, he says.

"Right now, it looks very effective, but there could be problems with it that we don't know about yet," Bengtson explains. "That's why it's so important that we explain the benefits and risks to people when they enroll in a trial."

The benefits of being involved in a clinical trial are numerous -- starting with the exceptional care that patients receive.

"We firmly believe that patients benefit tremendously from being involved in studies," says Dr. Seemant Chaturvedi, associate director of Wayne State University/Detroit Medical Center Stroke Program and an attending neurologist. "Patients simply get more attention. They may be seen in the office more often and are contacted frequently on the telephone."

Patients also have access to medications, procedures and treatments that are not available to the general public. For example, one of Chaturvedi's studies involves new acute medicinal treatments thought to reduce long-term effects of a stroke, if administered within the first six to 10 hours after a stroke. Some of the new medications being tested are available only to patients in a study.

Another benefit is the personal attention your case will receive.

"You have many different people reviewing the charts and checking the patient's progress, including the clinical trials office, the principal investigator and often a cooperative group that's interested in the study," says Decker. "That way, fewer things get missed -- and that's why, statistically, patients in clinical trials get better care."

Further, you can take pride in knowing that you are helping medical research -- often with a regimen that's as simple as taking a pill every day and visiting a nurse every six months or so. That's the schedule for Bill Vollano, 70, who is participating in a prostate cancer prevention trial at St. Joseph Mercy Hospital in Ann Arbor.

Although he is not at increased risk for the disease, Vollano approached his urologist and asked about participating in the study years ago. The prostate cancer prevention study is long-term, so he will be followed for many years to come. "It's really not an inconvenience at all, and I really wanted to help raise awareness of prostate cancer," says Vollano, a retired social worker. "This is a way in which I can contribute to knowledge and information, and I'm pleased to be able to help."

Possible side effects

But clinical trials are not for everyone, as there can be risks or drawbacks.

In many cases, while researchers work hard to see that you benefit from the treatment, the investigator also wants to learn about your illness, and not just treat you. In some cases, researchers are trying to determine the proper dose for a new medicine and are required to give a certain amount. They cannot personalize the dose to your particular situation.

If you receive a drug that works for you but is not yet approved by the FDA, you may not be able to continue taking it after the trial is over -- though exceptions are sometimes made.

Because many trials are randomized and double-blind, the medication you receive may not be new, or may not be medication at all.

Some illnesses or diseases have a current standard of care called "watchful waiting," meaning the patient is monitored but no action is taken. For these conditions, the trial may compare this standard with a new drug or treatment. As a participant, you -- and often the doctors and nurses -- do not know whether you are receiving a drug or a placebo. Some patients are uncomfortable with that.

And with the newest treatments and drugs, there may be side effects or long-term influences that are not yet known, Chaturvedi cautions.

"If you'll be taking a totally new compound or an experimental drug, it can be useful to ask how many human beings have been treated in the past. Potentially serious new side effects can emerge as more people take the compound, and you sometimes might need to treat hundreds of patients before you'll see those side effects. Whether you want to participate in something like that would depend on the extremeness of your condition," he says.

Because participation in a clinical trial is voluntary, you can leave a study at any time. However, many investigators conducting clinical trials prefer participants remain in the studies and be available for follow-up. And you may be asked to come in for follow- up visits after the trial is over.

Although there are always concerns, attitudes about research are changing, Decker says. Her Cancer Clinical Trials Office at Beaumont has grown tremendously in the 19 months since it opened, averaging 50 physician referrals each month. She signs about 25 patients per month to clinical trials and research studies.

"While some patients still fear being a guinea pig, others are incredibly well-informed and request to be part of a trial," Decker says. "They say they want the best possible treatment on the cutting edge of medicine, and a clinical trial can offer that."

Learning more

Patients are becoming better informed about clinical trials as well. The CenterWatch Clinical Trials Listing Service at www.centerwatch.com receives 450,000 visitors each month. The web site features information on more than 40,000 ongoing clinical trials, profiles of research centers and listings of investigational drugs and their results in clinical trials. Those who visit the site are often eager to participate in a study, says CenterWatch chief executive officer Ken Getz.

"Some patients, particularly those individuals facing severe and life-threatening illnesses, are looking to be proactively matched with clinical trials," he says.

Consent forms are becoming easier to understand as well. Such forms offer facts about the trials and specify the details of the trial, including what the new treatment is, how often it will be administered, what tests will be required to document your progress and possible benefits and risks.

"We make sure the patients understand that consent form, and we'll spell it out step-by-step so they feel comfortable," Decker says. "We want to give them all the information they need to make that decision and support them. But we never want them to feel pressured one way or the other."

These days, Deborah McDaris of Brighton revels in what she calls "suburbia galore." She wasn't sure she'd ever see her three daughters grow out of childhood, or be able to have the golden retriever she'd always wanted. Now she enjoys picking up the girls, ages 8, 5, and 3, from school and romping with their new puppy in the backyard.

She's happy to have been able to participate in the trials at Beaumont, and she hopes some day, some woman like her will have a better choice because of those trials.

McDaris herself is thankful to the 13,000 women who volunteered for the Breast Cancer Prevention Trials, halted early in 1998, because that study proved the effectiveness of tamoxifen -- which McDaris takes daily to help prevent a recurrence of her breast cancer.

Where to learn more about joining a study

Patients can take part in clinical studies covering a wide range of medical diseases, conditions and rare disorders affecting children and adults.

If you're interested in participating in a clinical trial to test ways of treating your disease or condition, the best place to start is with your physician or nurse. They already may be participating in such research. If not, you can be referred to a physician who is, or contact your hospital or institution of choice directly.

The Detroit Medical Center, Wayne State University, Henry Ford Health System, St. John Hospital and Health System, William Beaumont, the University of Michigan, Michigan State University, Oakland University, St. Joseph Mercy, Mt. Clemens General and many other institutions participate in local and national trials.

Many national advocacy and information groups also offer information about clinical trials.

If you're healthy, you're needed, too. The Clinical Research Volunteer Program at the National Institutes of Health uses almost 3,500 healthy volunteers in studies every year. Healthy volunteers provide researchers with important information for comparison with people who have specific illnesses. About 300 studies are available to healthy volunteers. Volunteers are compensated for their time. You can find information on these studies on the Clinical Center's home page, http://clinicalstud ies.info.nih.gov. Type in the keywords: healthy and normal.

The Internet has many other resources on clinical trials. Some sites to check:

* For information about cancer clinical trials: www.cancertrialshelp.org.

* For general information about clinical trials: http://clinicaltrials.gov. For the National Institutes of Health Patient Recruitment office: (800) 411-1222, (866) 411-1010 (TTY). E-mail: prpl @mail.cc.nih.gov.

* National Institutes of Health cancer trial information: cancertrials.nci.nih.gov.

* For a database of national clinical, go to www.centerwatch.com.

Know the realities

Clinical trials come with drawbacks. They include:

* Some patients in a double-blind trial do not receive the experimental medication. They may receive currently accepted medication for their condition or no medication at all.

* The newest treatments and drugs may cause unknown side effects.

* Researchers focus on learning about the illness, not treating an individual. So the dose of medication, or how it's administered, cannot be adjusted to suit individual needs.

* Even if the medication is effective, patients might not be able to continue taking it after the trial is over, if it has not been approved by the government.

Learning the lingo

Like most specialty topics, clinical trials seem to have a language all their own. Here is a brief glossary of terms you might hear associated with a clinical trial.

* Bias: Having an idea about the results of the study before the study takes place, and there is evidence to support it.

* Double-blind: A procedure to prevent bias in a study. Neither the patients nor the doctor and nurses know which patients are receiving which treatment. Only the researchers at a control office do.

* Eligibility: The qualifications required for participation in a trial, as determined by the researchers and the study protocol.

* Informed consent: The process by which potential participants learn about the clinical trial, including what the trial hopes to determine, what medications or treatments will be offered, how long the study continues, what the responsibilities of the patient are, and what the potential risks are.

* Phase I: The first studies of a new drug or treatment in people. These trials usually are used to determine how a drug should be given (as a pill or liquid, by injection into a muscle or dripped into the bloodstream) and how often.

* Phase II: Trials that continue to test the safety of the compound, along with how it works.

* Phase III: Studies that test a new drug, a new combination of drugs or a new surgical procedure in comparison to the current standard for treatment. There are generally two groups: The intervention group gets the new treatment, while the control group receives either the standard agent or a placebo.

* Placebo: A look-alike pill or compound that contains no active ingredient.

* Protocol: The action plan for a clinical trial that states what the study will do, how many people will be enrolled, who is eligible to participate, the tests that will be part of the trial, and what kind of information will be gathered.

* Side effects: Problems that can occur in conjunction with a clinical trial that are expected, such as dry skin or headache.

-- National Cancer Institute

The Detroit News, 05/16/2001 Page 6