Participants in Phase 1 Oncology Trials Not Vulnerable

Zosia Chustecka

January 16, 2008

January 16, 2007 — Because phase 1 oncology trials are typically carried out in patients who are in advanced stages of disease and investigate untried therapies, they offer a relatively low prospect of clinical benefit with the potential for serious risks. Hence, they have been cited as "paradigmatic examples of research that exploits vulnerable persons," and critics of these trials have called for special safeguards to be put in place.

However, a study of the demographics and health-status characteristics of individuals who participate in phase 1 oncology trials in the United States showed that they are not a conventional vulnerable population, say a team from the department of bioethics at the National Institutes of Health in Bethesda, Maryland.

In the January 14 issue of the Archives of Internal Medicine, the team reports the results of a review of 9841 people who participated in phase 1 oncology trials sponsored by the Cancer Therapy Evaluation Program between 1991 and 2002. These participants were predominantly white, middle-aged, and well educated. They were also likely to have private insurance, good performance status, and have already had their cancer treated before being approached to enroll in a phase 1 trial. Hence, there is little reason to assume that, as a group, these individuals have a compromised ability to understand information or to make informed and voluntary decisions, Christine Grady, RN, PhD, and colleagues conclude.

These trials do carry a big risk with relatively little benefit, the team acknowledged. In oncology, about 25% of these studies are testing a product that is being used in humans for the first time, and about 0.5% of participants die as a result of toxic effects, they point out. There are also data to suggest that tumor responses are seen in only 4% to 6% of participants, although a recent study suggested that the overall tumor response rates are higher than previously reported, at 10.6%. Hence, commentators have argued that participants are vulnerable.

Dr. Grady and colleagues take issue with this. They agree that phase 1 trial participants have serious disease and limited treatment options, which can constrain their decisions about research participation. But they point out that, as a group, these participants do not lack the cognitive capacity to make decisions and do not have general constraints on their personal liberties and voluntary decision making, although this might apply to particular individuals.

The team also disagrees with claims that patients with end-stage cancer are particularly vulnerable to exploitation by researchers. "Even extraordinarily difficult life decisions in trying circumstances can be made autonomously and rationally," they write. "Having few choices does not necessarily render one incapable of making a choice."

"Although individuals with end-stage cancer are influenced by the effects of ill health on their lives, they may still be quite capable of protecting their own interests and making rational informed choices, including those about research participation," Dr. Grady and colleagues write.

The researchers have disclosed no relevant financial relationships.

Arch Intern Med. 2008; 168:16-20 Abstract.


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