Clinical Trials and the "Therapeutic Misconception"

Faced with a dire prognosis, some cancer patients turn to clinical trials. But how well do they, or their doctors, understand the purpose of such trials? Not very, according to a recent survey {Lancet 2001;358:1772-77}. Oncologists questioned 240 participants in treatment-related clinical trials. Half had either relapsed or progressive disease, and two-thirds had been told they had less than a ten percent chance of surviving five years. Most patients felt that they had read the informed consent form carefully and had received adequate explanations. Yet this survey found that patients enrolled in clinical trials at Boston's top cancer hospitals generally misunderstood the purpose and potential benefit of such trials.

Seventy percent did not realize that the treatment being researched had not been proven to be the best treatment for their cancer. Half did not understand that the trial used non-standard treatments or procedures or that participation might carry incremental risks (63 percent). Many did not understand that they might not receive any direct medical benefit from their participation or that the purpose of a clinical trial was to benefit future patients, not themselves. They suffered from what the authors call the "therapeutic misconception," i.e., that clinical trials are designed to benefit those who enroll in them.

Such misconceptions were shared by many of their physicians, more than half of whom did not realize that the goal of trials was to benefit future patients. Other studies show a widespread pattern of misunderstanding among patients taking part in clinical trials and the doctors who refer them. Institutional Review Boards (IRBs) are supposed to protect patients from unethical practices. But in one Midwestern survey, only a third of principal investigators provided a detailed description of proposed studies to review boards, and a meaningful discussion of risks, benefits, and alternatives, was virtually non-existent {J Clin Ethics 1996;7:60-68}.

In a survey of cancer consultations, 83 percent of patients were never questioned to make sure that they understood what had been told to them. Before enrolling, patients have to sign "informed consent" forms. But, in one survey, the average time spent explaining the new treatment and getting consent was 10 minutes {Eur J Cancer 1999;35:1187-93}.

Where do these widespread misconceptions come from? I think they originate with health authorities who vigorously promote clinical trials. Most of what I read about the alleged benefits of clinical trials is misleading. For example, the National Cancer Institute lists various reasons to participate in clinical trials. Here is one of their top reasons: "Access to new drugs and interventions before they are widely available." This implies a therapeutic benefit to the current patient. They also state that "if the approach being studied is found to be helpful, you may be among the first to benefit." The very last thing mentioned is "an opportunity to make a valuable contribution to cancer research."

Yet, medical ethicists tell us that an altruistic desire to help future generations of patients is the primary reason to participate in a clinical trial. Deriving personal benefit, much less a cure, is so remote that you could sooner win the Powerball lottery. There is a strong temptation to talk about personal benefit, since the number of self-sacrificing martyrs to science has always been rather small.

Patients who are confronting advanced cancer should first of all learn what are the best state-of-the-art treatments. They should not enroll in clinical trials to please a favorite physician, since she herself may not understand the low probability of benefit. Sometimes, more promising treatments are available in specialized treatment centers than in hometown facilities. Second, patients should explore all viable alternative treatments, including those that are only available abroad. Finally, they should always cast a cold eye at clinical trials. Phase I trials are dose-escalation trials, which deal with unproven agents at unknown doses.

Conversely, phase III trials deal with better understood agents, but are by their nature randomized. Patients only have a coin-toss chance of receiving the desired treatment. Phase II trials are more promising since at least a reasonably safe and effective dose is known. There is no randomization and there may be some preliminary evidence of benefit. But patients should not enter any clinical trial that precludes them from taking other promising alternative treatments, as well. Their doctors should help them avoid the "therapeutic misconception" that is so rampant.