Consistent with previous research,6–9
we observed that many participants reported expectations of benefit that were much higher than the likelihood of benefit suggested by historical data from early-phase oncology trials. In past research, interpreting such findings has been challenging. In this study, however, we identified two important factors that should be considered in determining whether high expectations of benefit are signs of misunderstanding: (1) the type of expectation being queried and (2) what the patient intends to accomplish by providing a response.
Types of Expectation of Benefit
Among participants who were asked to indicate their confidence that the experimental therapy would control their cancer, the median expectation was 80 (out of 100), compared to a median expectation of 50 among participants who were queried in terms of relative frequency. This pattern was the same for between-subject and within-subject comparisons. Seriously ill patients may have more invested in believing in the success of their personal outcomes compared to a population outcome. This finding may also reflect the “better-than-average effect” in social psychology, which refers to the tendency of people to rate themselves better than most others.16
Thus, anyone concerned about early-phase trial participants’ high expectations of benefit should be careful to determine how patients were asked about their expectations.
Differences in the way the target questions were worded corresponded to important differences between two types of expectations, known in the philosophy of probability as belief-type
. (Kahneman and Tversky use the terms “singular” and “distributional.”17
) High frequency-type expectations should generate greater ethical concern about patient misunderstanding than high belief-type expectations. Consider, for example, a patient who says, “I know that fewer than 5 out of 100 patients will benefit on average; furthermore, I am 90% confident that I will be one of the people who will benefit.” One could judge the correctness of the first half of this statement by comparing what the patient said to what the patient was told regarding aggregate response rates in past early-phase trials. It is less clear how one would judge whether the patient is correct regarding the second half of the statement. Therefore, care should be taken during the consent process to communicate probability information in terms of relative frequencies and to query patients’ understanding in frequency-type terms when assessing understanding.
Participants’ intuitive understanding of what types of responses could be justified for each question type may have led to expressions of greater expectation of benefit in response to the belief-type question. In other words, the belief-type question seems to ask patients for a feeling about their confidence, whereas the frequency-type question seems to ask patients to make a knowledge claim. Expressions of feeling or opinion might have appeared less vulnerable than knowledge claims to charges of inaccuracy, thus allowing some participants to express greater belief-type than frequency-type expectations. Additional research is needed to identify the role that belief-type expectations play in patients’ decision making and how these expectations correspond to the frequency-type information provided to patients.
Patients’ Intentions When Responding to Queries About Benefit
The second major finding from this study concerns the justifications that participants gave for their responses to questions about likelihood of benefit. Typically, someone who asks patients to estimate the likelihood of benefit would like to assess the patients’ understanding. It is hoped that patients know this and so use their responses for the purpose of demonstrating their understanding. The justifications participants gave for their answers in our study suggest that this assumption is not always correct. If participants were trying to express their understanding of the likelihood of benefit, they might have justified their answers by, for example, citing some information conveyed during the informed consent process. We found, however, that very few participants cited such information to justify their responses.
This finding could be due to one of three possibilities: (1) participants did not receive information about the likelihood of benefit during the clinical trial consent process; (2) participants received information about the likelihood of benefit, but they did not understand what it meant and so generated their responses using other strategies; or (3) participants did receive and understand information about the likelihood of benefit, but they believed the interviewer was asking about something else or they elected not to incorporate that information into their responses. Regardless of the reason, it appears that few of the participants provided answers for the purpose of indicating their understanding of the clinical trial to which they had consented.
Rather than indicating their understanding, most participants provided answers that served as expressions of hope, positive attitude, and faith. Not surprisingly, this was especially the case with participants who expressed higher expectations of benefit. Participants explained their responses in terms of the utility and even the moral imperative of being optimistic. This finding strongly suggests that many participants used a question intended to elicit their understanding of the likelihood of benefit as an opportunity to give a rallying cry—to reassure themselves and others that they would succeed. The finding is consistent with an ethos common among patients with cancer and their care providers to cultivate a positive attitude and minimize doubt.18,19
Given that 85% of the participants who reported higher expectations (> 70) appeared to be fulfilling an obligation or desire to express a positive attitude, it would be unwise to interpret all expressions of high expectations of benefit as a misunderstanding about the nature of the trial, and hence a failure of the informed consent process. Our findings suggest that it is difficult to assess patients’ understanding of the likelihood of benefit without triggering patients’ need or perceived obligation to express something positive. Our research team is now conducting a prospective randomized trial based on the data presented here to evaluate strategies for assessing understanding in this context.
This study has several limitations. First, the participants were from two large academic cancer centers, so findings might not generalize to other settings. Compared to patients in other clinical settings, more participants in this study described themselves as white and non-Hispanic and reported higher levels of education and greater household income. It is unclear whether patients with other socioeconomic characteristics would express equally high expectations of benefit. Second, although 63% of the patients we contacted agreed to participate in the study, it is possible that the results do not reflect the expectations or the reasons for those expectations among patients who declined to participate. Nevertheless, our data can speak to the group of patients about whom bioethicists are most concerned—those who express high expectations of benefit. Third, we obtained the data through relatively brief interviews using interviewers who were not known to the participants. Participants might have expressed different expectations of benefit if the interviews had taken place over a longer period of time or if the interviewers had been people with whom the participants already had some rapport. However, any effort to enact standardized querying of the consent process would likely involve relatively brief assessments of patients’ understanding, possibly by someone unknown to the patients. Thus, while we might have obtained different data using different methods, we believe our approach is similar to what would be used to query patient understanding during an informed consent auditing process. Finally, the findings are based on a relatively small sample from a pilot study designed to inform a large-scale randomized trial that is currently underway.
These data represent the first in-depth exploration of expressions of high expectations of benefit by participants in early-phase clinical trials. Some researchers have assumed that patients are describing their understanding of the likelihood of benefit when expressing such expectations. Our findings suggest, however, that the wording of questions about likelihood of benefit shapes the expectations that patients express. Thus, investigators should disclose likelihood of benefit and query understanding in terms of relative frequency rather than belief-type probabilities. The findings also suggest that patients who provide the highest expectations of benefit may not do so to communicate their understanding, but rather to register optimism in the service of achieving good outcomes. Although this conclusion suggests that patients’ expressions of high expectations of benefit might not always be a significant ethical concern, more empirical work is needed. We are currently collecting data to clarify the meaning of high expectations in a larger sample and to examine methods for assessing understanding in this context. Future research is also needed to elucidate the consequences to patients of expressing high belief-type expectations in the presence of low frequency-type probabilities.