SHOULD YOU JOIN A CLINICAL TRIAL? TAKE TIME WITH THE INFORMED CONSENT PROCESS.
Maryann Napoli

06/01/2002
HealthFacts
Copyright 2002 Gale Group Inc. All rights reserved. COPYRIGHT 2002 Center for Medical Consumers, Inc.

Some doctors suspected that the high rate of blindness among children born prematurely was not due to their low birthweight and pre-term birth, but instead, was caused by the then standard practice of giving oxygen right after delivery. Their suspicions were confirmed and the practice ended decades ago, but only after a clinical trial was conducted in which half the pre-term infants had been given oxygen and the other half were left untreated.

Similarly, mastectomy might have remained the standard treatment for women with early breast cancer, had it not been for the thousands of women who agreed to be randomly assigned to receive either a mastectomy, or breast-sparing surgery with, or without, radiation therapy. All had the same survival rate at the initial followup of eight years, thus ending the nearly 100-year reign of breast removal as the one and only treatment for early breast cancer.

The randomized clinical trial is the foundation of medical science. And unless people agree to participate in clinical trials, medical care would continue to be based on hunches and observations, many of which are dead wrong or outright harmful.

The 50% chance of being randomly assigned to take a placebo (inactive pill) is troubling to many prospective trial participants who want to take the drug that is being researched. But most clinical trials show that a significant percentage-- usually about 30 to 40% -- of people on the placebo get better. This is as true for studies of people with terminal cancer pain as it is for people with hypertension. The phenomenon is thought to be due to the expectation of a benefit or the normal waxing and waning of any illness, including the most serious. If placebos were not given in drug trials, we might never have learned, for example, that antidepressant drugs like Prozac, Paxil, and Zoloft are as effective as placebos. Some trial participants did better on placebos than those on the drug.

Often, physicians can unwittingly undermine clinical trials by describing a new therapy as "cutting edge." The whole point of a clinical trial is to find out whether the new treatment actually is an advance over the standard treatment. Calling a treatment "cutting edge" prematurely can backfire and seriously delay finding out whether it lives up to initial hopes. That is what happened with high-dose chemotherapy (HDC) with bone marrow transplantation for advanced breast cancer.

Many women, desperate for a cure, were told this expensive, highly toxic procedure was their "best hope" by some cancer specialists, who were convinced of its superiority over standard chemotherapy. They undercut other cancer doctors who were trying to recruit women for the clinical trials designed to compare HDC with standard chemotherapy. Two years ago, several trials finally published their results, which found HDC to be no more life prolonging. A speedier answer would have spared thousands of women the anguish of HDC's toxic side effects, now known to have caused the deaths of about 20% of all who got the treatment in the 1980s.

But joining a clinical trial can involve serious, sometimes fatal risks. The federal government has instituted safeguards (see below) to ensure that people fully understand what they are getting into. Yet disturbing misunderstandings come to light every time a survey is conducted of people who have participated in clinical trials. Most recently, CenterWatch, an organization that maintains a roster of clinical trials on its Web site, found that the majority of those who entered clinical trials did not understand the risks. And ten percent did not even read the consent form.

Even more alarming findings came from a survey focused on the quality of informed consent in cancer trials. It was conducted in Boston and published at the end of last year in The Lancet (11/24/01). Questionnaires were sent to 207 people with cancer who had recently participated in a clinical trial, as well as the trial investigators. The survey was conducted by Steven Joffe, MD, of the Dana-Farber Cancer Institute, and colleagues at other medical centers in Boston.

90% of the cancer patients reported that they were satisfied with the informed consent process and considered themselves to have been well informed. However, their responses also showed that 70% had not understood that the treatment being researched had never been proven to be the best for their cancer; and 25% had not understood that trials are done mainly to benefit future patients. Two people did not know they had participated in a clinical trial. Answers from the trial investigators were also alarming. Only 28 of 61 recognized that "the main reason for clinical trials is to benefit future patients."

This survey included people who had participated in phase I, II, and III drug trials. Phase I trials look at dose toxicity, starting a low doses that increase as new participants join the trial. And Phase II explores the first hints of efficacy, such as tumor shrinkage and improved test results. Clinical trials do not get to the question of whether the drug actually works until the phase III, which usually includes many more participants than the earlier trials. Only 22 of the 50 people who had participated in the phase I trial knew that the goal involved escalating doses purely to determine maximum safe dose.

What made these survey results so discouraging is the fact that the participants did not report being pressured. On average, investigators took a great deal of time with the participants, most of whom took several days to make their decision. The survey results showed several ways the informed consent process could be improved. Those who took their time and had a nurse present at their consent discussion were more knowledgeable than those who did not. And higher knowledge scores were shown among the people given consent forms from hospitals that used the format provided by the National Cancer Institute.

For More Information:

-The National Cancer Institute offers a free "Guide to Understanding InInformed Consent" and a registry of cancer trials at its Web site (www.cancer.gov). People without immediate access to the Internet can call the NCI-sponsored hotline 1(800) 4-CANCER. (Everyone has access to the Internet via the public library system.) Though focused on cancer treatment and prevention, most of the NCI information will be helpful to people participating in trials for other diseases.

-ECRI, an independent nonprofit health services research agency, offers a a free guide, entitled, "Should I enter a clinical trial?" on its Web site (www.ecri.org).

-CenterWatch, a Boston-based publishing and information services cocompany, keeps a registry of clinical trials internationally, in a broad range of fields, such as dental surgery, obstetrics, and ophthalmology, on its Web site (www.CenterWatch.com). The organization just published a 300-page book entitled, "Informed Consent." The cost is $16.95.

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MaMaryann Napoli is the associate director of the Center for Medical Consumers in New York City.