Important concerns have been raised about the ethics of phase 1 clinical trials in oncology. In previous research, many patients have reported high expectations of personal clinical benefit from phase 1 trials. In the project leading to this proposal (RO1CAIOO77I), the investigators examined what patients mean when they report high expectations of benefit and whether these reports reflect poor understanding about the phase I trial. Using a mixed-methods approach, the investigators identified several limitations on the ability to truly understand what high expectations mean to every patient. In continuing their work, the investigators propose to evaluate the ethical significance of high expectations of benefit from a different perspective. Specifically, the investigators propose to address whether high expectations of benefit are harmful to patients in phase I trials. Many patients will not experience good clinical outcomes from phase I trials. Decision affect theory predicts that patients with higher expectations of benefit might experience greater distress and negative feelings about their participation. There are rio data available to determine when high expectations of benefit reflect a helpful coping mechanism rather than a potentially harmful form of denial. This gap in knowledge presents serious difficulty, because there is no evidence to guide clinicians and researchers in deciding whether to foster or discourage patients'expressions of high expectations. With a renewal of ROICAI 00771, the investigators will collect preliminary data that will help clinicians, researchers, and persons charged with human subjects protection to understand the consequences of high expectations of benefit among participants in phase I trials. The investigators will achieve this objective by pursuing 3 Specific Aims: (1) To explore associations between expectations of benefit and later physical and mental well-being among participants in phase I trials who experience disease progression. The investigators hypothesize that higher expectations are associated with greater increases in depression and anxiety, and they will explore associations with physical functioning. (2) To explore associations between expectations of benefit and later perceptions of the consent process among participants in phase I trials who experience disease progression. The investigators hypothesize that higher expectations are associated with more regret concerning the decision to enroll in the trial. (3) To explore relationships between expectations and later experiences among phase I research participants who have nonprogressive disease at the time of their first disease reevaluation. The investigators will accomplish these aims in a prospective study using structured interviews of patients immediately after enrollment in a phase 1 trial and follow-up interviews I week after the patients receive the results of their initial disease reevaluations. The study will generate preliminary data that address an important gap in understanding of research participants'welfare in phase 1 oncology trials. If high confidence in a good outcome has negative consequences for patients with poor clinical outcomes, this finding might suggest that clinicians and researchers should try to reduce patients'high expectations. However, if there are no negative effects of high expectations, clinicians and researchers might consider whether to allow such therapeutic optimism in patients who have demonstrated clear understanding of the trial to which they have consented.

Public Health Relevance

Some patients in phase 1 cancer clinical trials report very high expectations that they will receive significant clinical benefit from their participation. Clinicians and bioethicists are concerned that these patients may experience greater depression, anxiety, and other negative reactions when patients'clinical outcomes are poorer than expected. Data from the proposed study will help guide clinicians and researchers in their interactions with patients in phase I trials who express high expectations of benefit.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-HOP-J (90))
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Witherspoon, Kim
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Duke University
Schools of Medicine
United States
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