UNREALISTIC OPTIMISM FOR EARLY PHASE TRIALS

February 9, 2011 — Cancer patients participating in early-phase oncology clinical trials exhibited "significant levels of unrealistic optimism," according to the authors of a survey of patients at a New York City comprehensive cancer center.
Unrealistic optimism is defined as "the product of a bias in which the person believes that she is more likely to experience positive outcomes . . . than others similarly situated," explain the study authors, led by Lynn Jansen, PhD, from the Oregon Health and Science University in Portland.
The results, from a survey of 72 patients enrolled in various phase 1 and 2 trials, are reported in the January–February issue of IRB Ethics & Human Research.
Early-phase drug trials have long been a concern among medical ethicists because they are ripe for unrealistic optimism, suggest the authors.
"It is widely recognized that early-phase trials are not designed to provide direct therapeutic benefit to those who participate in them," they write. But even while understanding this, participants still thought that they would benefit, the study showed.
For example, the survey revealed that a significant number of respondents had "unrealistic optimism" about 3 positive outcomes (and thus believed that they were more likely than other clinical trial participants to have these outcomes):

• the possibility of their cancer being controlled by the trial drugs (P < .05)
• experiencing health benefits (P < .001)
• not experiencing adverse events from the trial drugs (P < .05).

However, they were not found to have unrealistic optimism about 2 other outcomes — having their cancer cured by standard drugs or by drugs in the trial.
Not a Lack of Understanding
Did the participants, nearly two thirds of whom had college or postgraduate degrees, understand the nature of early-phase trials? Yes, say the investigators.
"We found no significant relationship between unrealistic optimism scores and misunderstanding about the purpose of the trials," they report.
The findings are "important results," say the investigators, because "it has been widely assumed" that patients' expectations were either a result of a failure to understand the nature of these trials or expressions of a "hopeful state of mind."
So what's at work here?
The study authors do not know, but they think that unrealistic optimism has the "potential for compromising informed consent of research participants." They also believe that the consent process needs improving and that "social-psychological factors" need to be addressed.
"It's not clear how you manage this cognitive problem," said Arthur Caplan, PhD, a medical ethicist at the University of Pennsylvania in Philadelphia, and a video blogger on Medscape Medical Ethics.
However, Dr. Caplan, who was not involved in the study, agrees that social-psychological factors are at play. The drug trial participants in the survey have a "very American outlook," which might be described as a "gambling attitude" — that they will be the lucky one, said Dr. Caplan.
The unrealistic optimism found in the survey "reflects deep cultural values of capitalism and American entrepreneurialism" — that winners take chances and individuals can triumph over great odds, he explained.
More Than a Positive Outlook
The study survey took place at the New York Medical College and St. Vincent's Medical Center in New York City. The participants, 98% of whom had either a blood cancer or myelodysplastic syndrome, completed the Comparative Risk/Benefit Assessment Questionnaire.
The questionnaire asked participants to rate whether their chances of experiencing each of a series of 5 events were greater than, less than, or about the same as the chances of other patients participating in the same cancer research trial.
The 5 events, which included being cured and having their cancer controlled, are summarized above.
Participants were then asked an open-ended question: "What is your understanding of the purpose of the cancer research trial in which you are going to participate?" The researchers summarized the responses using a number of categories. They report that most of the respondents (72.9%) said that the purpose of the oncology trial in which they were enrolled was to "advance generalizable knowledge with the potential to benefit future patients." In short, most understood the nature of an early-phase trial. Furthermore, participants who misunderstood the purpose of an early-phase trial did not have significantly different questionnaire scores from those who correctly understood the purpose.
A statistical t test determined that there was no significant relation between responses to the "purpose question" and the optimism scores (with respect to the 5 cancer-related events).
The authors explain that the study results exceed what is generally understood to be a positive outlook. "Our study suggests that the optimism expressed by patient-subjects in early-phase oncology trials reflects something more than a disposition to think positively," they write.
"It is possible that a participant in a cancer trial might express hope that the trial will control his cancer, but not express the view that he is any more likely than similar others to benefit from the trial," they explain.
The study was supported by National Institutes of Health-National Cancer Institute. The authors have disclosed no relevant financial relationships.
IRB: Ethics & Human Research. 2011;33:1-8.