Human language is complex. It is not merely a mode of expression, but it is used as a tool to get things done. When a patient enrolling in an early-phase oncology trial responds to the inquiry, “What do you think the chances are that this treatment will control your cancer?” and he or she replies, “Eighty percent,” a philosopher of language would ask, “What is the patient doing with the phrase, ‘Eighty percent’?”28
Corroborating previous findings, when we asked our participants who had enrolled in early-phase oncology trials about their expectations of therapeutic benefit, they gave answers that were generally much higher than those historically reported for patients participating in such trials.2–4,13
When asked to explain how they arrived at their answers, however, we found little evidence that what they were “doing” was reporting misinformed or confused views about data. Rather, consistent with observations reported by Kim et al,29
what they appeared to be “doing” was expressing attitudes of optimism and faith.
For many participants, expressing optimism was deemed important because they believed expressing hope and having an optimistic attitude would actually improve the likelihood that they would experience a therapeutic benefit. Many based this belief on a type of folk psychology. Such beliefs have been popular from the times of Hippocrates to Percival to Karl Menninger to the present.30–35
Other participants understood the connection between hope and outcomes as something established by science, even though the actual data are, at best, conflicting.36,37
Studies reporting that “hope helps” might be more likely to be reported in the media, so that patients come to believe that this is incontrovertibly true. Furthermore, a widespread set of background cultural norms favors an optimistic attitude for patients, influencing their responses to inquiries about their expectations of therapeutic benefit upon enrolling in a clinical trial.35,38
Christian scriptures say, “faith is the substance of things hoped for” (Hebrews 11:1). In other words, those who hope must have faith. Our participants, living in a secular age, often based their hopes for therapeutic benefit from clinical trials on their faith in medicine. Sometimes this faith in medicine and science was mixed with religious faith—God and medicine.39
Other patients only expressed religious faith—that the trial would keep them alive and God would perform a miracle. Another meaning of faith, though, is not belief but trust—faith in a person or group of persons or a human institution. A number of participants who used the word “faith” appeared to be using it in this interpersonal, relational manner, applying it to physicians and cancer centers to justify why it is that they had the hopes they did.
Participants also saw themselves engaged in a battle—a struggle in which surrender was not an option.18
This metaphor is one of our culture’s dominant metaphors in describing cancer.33
for instance, has documented the history of the celebrated war on cancer, which continues unabated today. Talk about hope and battle has also been linked to cancer patients’ sense of personal agency.41,42
Individual participants in our study used metaphors from sports or the military, also deeply embedded in our culture, to describe their optimism as the proper attitude in the face of difficult odds.35,43
It was clear from these interviews that cultural expectations of faith and hope are not only generated by physicians, nurses, and medical scientists.33
Families, friends, and religion all encouraged optimism. These cultural norms may be especially well-developed in cancer centers, where optimism may serve as a defense mechanism for staff as well as for patients. Many of the clinical trial participants we interviewed seemed to report both that they had been informed about the uncertainty of the trials’ outcomes, and also that they were encouraged to maintain hope. The latter might serve as the dominant message, even if patients are fully informed at the time of consenting for the trials. It is also likely that the patients are a preselected group, drawn by their faith in medical science to high-profile institutions as potential sources of a “last hope.”
Another cultural expectation seems to be that certain social roles, such as that of spouse or parent, call for expressions of optimism in order to reassure or even “protect” loved ones. Several participants reported that their optimistic expressions were motivated by such familial concerns, with a purpose far different from expressing an understanding of data.
By and large, our participants seemed to understand the purposes of their clinical trials, that the outcomes were unknown or uncertain, and that historically, populations of patients who have enrolled in early-phase clinical trials were unlikely to therapeutic benefit. Only one participant appeared to labor under a full-blown therapeutic misconception, believing that every aspect of the trial was designed for his individual therapeutic benefit (F25: “The purpose is to cure colon cancer”). Despite this, most participants estimated their own chances of individual therapeutic benefit as quite high, showing evidence of a possible therapeutic misestimation rather than a full therapeutic misconception. Yet, in giving their high estimates of expected outcome for themselves, many distinguished themselves from other participants in the same trial, whose chances of therapeutic benefit they estimated to be closer to historically low figures. These patients were optimistic despite their factual knowledge of the low frequency with which patients benefit from early-phase trials, a phenomenon that has been dubbed “therapeutic optimism.”
Most participants also reported a secondary altruistic motive for enrolling in a trial. Many reported a primary hope that they would benefit individually, and a secondary hope that others might benefit in the long run even if they did not themselves benefit individually. Previous studies, using closed-ended questions, have downplayed the role of altruism as a motive.4,19
More open-ended and qualitative studies, such as ours, suggest altruism has a significant secondary motivating role.18,21
Notably, we found a hermeneutic association between the way optimistic expressions function as performative expressions for patients as individuals and the concept of engaging in an altruistic battle against cancer. Participants often expressed both justifications for their optimistic expressions in the same utterance. In a sense, both are performative expressions—one expressing the belief that positive thoughts will affect their outcomes as individuals, and the other expressing the belief that their individual battles are part of a greater battle by society against cancer, the outcome of which depends, in part, on their own positive attitudes.
This study obviously does not address all of the ethical questions that swirl around the so-called therapeutic misestimation. It does, however, help to define more clearly where the true ethical questions lie.
It does not appear that what most of our participants were “doing” when they reported high expectations of individual therapeutic benefit from participation in clinical trials was giving a confused report on their understanding of trial statistics. To the extent that a patient can say, “I know that historically less than 5% of patients enrolled in phase I clinical trials have benefited,” then the potential ethical problem is neither a failure of adequate disclosure by the investigators nor a failure of adequate comprehension by the patient. If this is true, then attempts to improve the informed consent process by new techniques of communication designed to improve comprehension may be missing the mark.
What patients appear to be “doing,” in many cases, is expressing faith and optimism. The belief that personal will can effect a change in the course of bodily disease, the conflation of hope and optimism, and the notion that the medical system embodies and defines the limits of hope all may be constructs of a particular historical moment in our particular culture.
It is uncertain what the ethical implications of this faith and optimism might be. On the one hand, it might be important to encourage such expressions. If an optimistic attitude really does improve outcomes, then there might be morally good reasons for encouraging it. If, for most patients, optimism is a critical psychological defense mechanism, then it might also be good to encourage optimism, at least up to the point that it becomes dysfunctional denial. On the other hand, these expressions of optimism might be signs of the cognitive bias known as “unrealistic optimism.”22
That might make patients who are offered participation in early-phase oncology trials especially vulnerable as research subjects, suffering from a cognitive bias that could lead to poor decision making and coercion. It is also possible that these expressions of optimism are signs that these patients are being subtly influenced by cultural expectations both inside and outside the medical research community, pressuring them to enroll in order to prove that they really have not given up hope. Several previous studies have suggested that patients feel family pressure to enroll in clinical trials.4,15
Our data suggest that the pressure to enroll may be part of a broader expectation that they “think positively,” with enrollment in the trial serving as proof that they have not “given up hope.”
As an empirical investigation, this study cannot answer the ethical questions it raises.44
Like any qualitative study, it is also difficult to generalize beyond this small group of cancer patients. While our study population reflects the national demographics of cancer trial populations,45
it is not known how a more racially and culturally diverse population might have responded to the interview questions. Our measure of distress is not validated, but this part of the study was only exploratory and should be investigated more carefully. While we have taken appropriate safeguards against bias, all texts require interpretation and the transcripts of these interviews are a text. Moreover, since we did not observe their interactions with clinicians, we are limited by patients’ understandings, memories, and potential recall bias.
Despite these limitations, we found strong evidence that expressions of high expected therapeutic benefit among these early-phase trial participants were more likely to represent expressions of optimism than reports of factual knowledge. These findings also suggest that reports of high expected therapeutic benefit among research participants constitute a complex phenomenon and that studies designed to disentangle a variety of forms of therapeutic optimism, therapeutic misestimation, and therapeutic misconception will need to be carefully designed. Further empirical research is needed before determining the ethical significance of these phenomena.