Clinical trials want you Plenty of researchers need volunteers, but you have to know how to find them - and what to look for once you do

By Lorilyn Rackl, Daily Herald Health Writer 05/13/2002

Dr. Joel Charrow of Children's Memorial Hospital in Chicago didn't expect to get a long list of patients clamoring to enroll in his clinical trial of a promising new treatment for Fabry disease.

After all, the genetic disorder, which often kills people by age 40, is rare. And simply having the disease isn't enough to qualify for the study. To join, patients must have mild to moderate kidney problems, a common side effect of the illness.

Still, Charrow figured he could get at least five patients signed up. Several months later, he's far from that goal.

"So far, we have one," said Charrow, head of genetics at the Chicago hospital.

Whether you have a rare disorder like Fabry or something far more common such as cancer, diabetes, lower back pain or acne, chances are there is a clinical trial somewhere looking for people like you.

The problem is they often can't find you.

There are currently about 6,000 new drugs, procedures and treatments being tested in 80,000 different locations around the country. But according to a new report from the Association of Clinical Research Professionals, more than 80 percent of clinical research trials are being delayed because there aren't enough volunteers.

This can cause major setbacks for scientists - and patients.

"The development of new therapies is dependent entirely on having people who are willing to try them," Charrow said.

Even when patients are willing and able, locating the right clinical trial can be a challenge. The Internet, however, is making that information easier to find.

With the click of a mouse, patients can locate clinical trials that their own doctors might not even know about. Some services let people sign up for regular e-mails alerting them to the latest studies.

While it still might take some hunting and homework, patients say it can be well worth it - especially when you've run out of options.

That was the case for Ray Dittmann.

Doctors diagnosed the Schaumburg man's pancreatic cancer in January 2000.

Surgeons at Alexian Brothers Medical Center in Elk Grove Village removed the tumor, but Dittmann still faced grim odds. His chance of being alive two years later: between 20 percent and 40 percent.

Dittmann's oldest daughter did some searching on the Internet, made a few phone calls and found a study testing the drug gemcitabine in patients like her father.

For would-be participants like Dittmann, assessing the risks of a clinical trial is just as important as finding the study. Dittmann decided to take the chance.

"I knew it was serious and I had to do something," the 65-year- old man said. "I'm glad I did. As of right now, everything is fine. I'm thankful every day I get up and see the sunshine, or clouds or whatever."

Surfing for studies

The Internet has evolved into an invaluable tool when it comes to linking patients with researchers.

Some comprehensive sites canvass the medical world for trials. CenterWatch, at www.centerwatch.com, lists studies sponsored by both government and industry. It also links to a clinical trials matching service, but the site warns that such services might have an incentive to match patients with a trial that isn't as good an option as others outside their listings. The services typically work on the "bounty" model, getting anywhere from $300 to more than $1,000 for every patient they deliver to trials.

Though CenterWatch gets a fee from industry trials it lists, it doesn't recruit patients or sell patient information. It lets consumers sign up for a free, confidential e-mail message whenever a clinical trial for a particular condition is listed on the site. It also offers to notify users about newly approved drugs for specific medical conditions.

Patients who prefer to stay away from commercial sites altogether have plenty of other options.

ClinicalTrials.gov was launched two years ago primarily to list government-funded trials. Industry-sponsored trials soon will be added, now that the Food and Drug Administration ordered manufacturers to list all trials testing the effectiveness of drugs for serious or life-threatening diseases on the site, which is www.clinicaltrials.gov.

Almost every major disease or condition now has a group of patient activists who have set up their own mom-and-pop Web sites or regular mailing lists to help find trials and share information with each other.

Some can be found fairly easily by merely entering both the name of a disease, such as "diabetes," and the words "clinical trials" in a search engine such as Google.com.

Knowing the risks

Finding a trial is just the first step. Then it's up to the patient to understand the risks and implications of medical research.

Trials are just that - experiments on human subjects - and there are no guarantees of a better outcome.

That's no doubt part of the reason only 3 percent of cancer patients are enrolled in clinical trials.

"With more common diseases and less disabling diseases, people may take the attitude, 'Let some other guy be the guinea pig,' " Charrow said.

Part of the public's apprehension toward clinical research likely stems from the well-publicized deaths of patients in clinical trials at the University of Pennsylvania and Johns Hopkins.

A new survey by Harris Interactive finds that about two-thirds of adults aren't confident that patients get high quality care in clinical trials and worry they'll be treated like guinea pigs. They also fear they won't get accurate and honest information.

But federal data show that it's rare for people to die from negligence or mismanaged care in clinical trials. Side effects and reactions are much more common. According to the Food and Drug Administration, one out of 10,000 patients has died from the effects of drugs being studied, but one in every 30 study subjects will have a serious adverse event.

Yet, people in clinical trials aren't always aware of the risk. A recent survey by CenterWatch found that even after signing required consent forms, 14 percent of study participants didn't understand they could suffer side effects during an experiment.

"I didn't even bother reading the consent papers," said Ralph Stephens, a 69-year-old Niles man who entered a clinical trial at Northwestern Memorial Hospital in Chicago after his leukemia stopped responding to standard therapy.

Stephens' wife, Linda, did read the consent forms. And the risks she read about worried her so much, she didn't want her husband to join the study. Stephens managed to change her mind.

"If participating would further the progress of research, it was worth it - even if it didn't help me," Stephens said.

It turns out the experimental chemotherapeutic agent did help Stephens.

"If I had not gone on the clinical trial, I would not be here," he said.

His cancer went into remission, although it's now back. And Stephens is in another clinical trial.

New help for patients

Wading through the scientific jargon and weighing the pros and cons can be a tough task for sick patients.

Several new campaigns strive to take away some of the mystery surrounding medical experiments and to help patients know what questions need answering before they sign up.

Researchers and patients alike say this kind of education is sorely needed.

"We didn't know enough even to ask questions," recalled Fernando Segura, a Pennsylvania engineer who helped his wife, dying of lung cancer, enter a study of a new treatment. In the end, she was too ill to benefit.

"It is frustrating," Segura said. "You feel like you're at everyone's mercy."

Last month, CenterWatch published a new consumer guide that explains in detail the risks and benefits of volunteering. Priced at $16.95, "Informed Consent" includes an introduction by Paul Gelsinger, whose 18-year-old son died in a gene therapy trial at the University of Pennsylvania.

Clinical trials offer "great hope to those in desperate circumstances," Gelsinger says, but he warns that people need to be informed about the risks and especially about any financial interests researchers may have in the outcome. "I trusted a system that needlessly killed my son, and I'm working to make it aware of the problems we uncovered," he says.

The "Informed Consent" guide and the ClinicalTrials.gov Web site provide checklists of questions all patients need to ask before enrolling in a study.

Another new - and free - guide called "Should I Enter a Clinical Trial?" gives an easy-to-understand overview of clinical studies and points out what questions need answering before a person decides to enroll in research.

Risk isn't the only concern, the guide stresses. Participants must understand:

- That they can drop out for any reason.
- Who to go to if their illness worsens or they suffer a side effect.
- Who's funding the research and whether the doctor owns stock in the therapy's maker or has another conflict of interest that might affect patient welfare.
- While many trials are free, some incur costs that not all insurers cover.
- What tests and checkups are required, important in planning travel, lodging, child care and other possible commitments.

The comprehensive guide, published by the nonprofit health analysis agency ECRI and the American Association of Health Plans, is available free online from the ECRI and AAHP Web sites.

The Wall Street Journal and the Associated Press contributed to this report.

What you should know about clinical trial phases

There are generally four phases of clinical trials. Here's a look at each of them:

Phase I
This usually marks the first time an experimental drug or device has been tried in humans, so researchers are more concerned with finding out how safe the therapy is rather than how well it works.

Participants in phase I studies often haven't responded to standard therapy, so these trials many times are seen as a last resort.

Patients should understand that this early stage of research carries the least potential benefit and the greatest potential risk because the only evidence at this point is from animal or laboratory studies or from results of the treatment in some other disease. Published articles have found that only 3 percent to 5 percent of patients end up benefiting in phase I cancer trials.

Phase I trials have no control groups, meaning all patients receive the experimental treatment. Researchers usually enroll only a small number of participants - from 10 to 80. The studies often are brief, too, lasting from several weeks to a few months.

Phase II
If a phase I trial hasn't uncovered serious risks or problems for patients, the trial might move on to the second phase, where researchers will be looking to see how well the drug or device works.

A control group (patients receiving a different therapy or a placebo) might be included. For life-threatening diseases, placebos are rarely used. Patients might be randomly assigned to be in the control group or the experimental treatment group.

These trials typically take several months or years, and anywhere from 50 to a few hundred patients might be enrolled in the study.

Phase III
If the first two phases produce positive results, the study sponsor likely will move on to a phase III trial to better define the benefits and risks of the therapy.

Phase III trials usually include the random assignment of patients into a control group or experimental treatment group. The process may be "blind," meaning the patients and/or the researchers will not know what treatment participants are getting.

Hundreds to thousands of patients might be enrolled in the study, which could last up to several years.

The purpose of phase III trials is to find out how well the drug works in a wider spectrum of patients and to determine optimal doses, among other things. These trials also give researchers a chance to spot less common side effects.

Patients in phase III trials have a better chance of benefiting from the therapy than they would in earlier stage studies, but it's important to remember that the safety and effectiveness of the drug or device isn't well established.

Phase IV
Sometimes called a postmarketing study, this final phase of the trial typically gets conducted after the Food and Drug Administration has approved the marketing of the drug or device.

These usually are large studies and are sometimes required by the FDA as a condition of approval.

The point of more study is to see how well the treatment works in a broader mix of patients and to gather even more data about side effects and their frequency. Companies also might do these trials to compare their product with a competitor's.

By phase IV, risks are much better outlined and some benefit has been shown.

- Lorilyn Rackl

Sources: ECRI (formerly the Emergency Care Research Institute) and the American Association of Health Plans.

What to look for in trial ads

The Food and Drug Administration says the following information should be included in ads looking to recruit clinical trial participants:

-Name and address of the clinical investigator and/or research facility
-The condition under study and/or the purpose of the research, in summary form
- Criteria that will be used to determine eligibility for the study
- Brief list of participation benefits, if any (e.g., a no-cost health examination)
- Time or other commitment required of participants
- Location of the research and person or office to contact for further information

Sources: ECRI (formerly the Emergency Care Research Institute) and the American Association of Health Plans.

How to find clinical trials

Plenty of private companies, organizations and federal agencies list ongoing clinical trials. Some of these groups also match patients and trials, but consumers should be aware that the company might be getting paid for that service.

Acurian
Consumers can search this for-profit company's database of more than 42,000 clinical trial sites for free. Patients search by medical condition and state to find available trials.

AIDS Clinical Trial Information Service
Government site that lists federally and privately funded HIV/ AIDS clinical trial information.

CenterWatch
For-profit company has free information about more than 41,000 industry- and government-sponsored trials. Patients can get e-mail updates when new trials appear on the site.

Coalition of National Cancer Cooperative Groups
Cancer patients can find trials sponsored by groups such as the American College of Surgeons Oncology Group on this nonprofit organization's site.

HopeLink
Patients can get information about cancer trials sponsored by government and industry, and the for-profit group recently expanded the site to include trial information about other diseases.

MyCure
For-profit patient and clinical trial matching service. No charge to patients who register for information.

National Cancer Institute
Government-sponsored database of roughly 2,000 clinical trials related to cancer.

National Institutes of Health
Federally funded clinical trials listed for a wide range of diseases and conditions. Now includes industry-sponsored trials, too.

Office of Research on Minority Health
Government site that lists clinical trials specifically addressing minority health issues.

Pharmaceutical Research and Manufacturers of America
Patients can search this drug industry site by disease, drug name, company or indication for the drug's use. You can sign up to receive free updates on new drugs in development.

Radiation Therapy Oncology Group
Cancer study research group site lists several dozen active studies that involve radiation therapy either alone or in conjunction with surgery and/or chemotherapy.

Sources: ECRI (formerly the Emergency Care Research Institute) and the American Association of Health Plans.

Source: 05/13/2002
Chicago Daily Herald