Understanding Patient Expectations of Treatment Outcomes

人们对肿瘤临床1期试验的伦理问题提出了重要的关注。在之前的研究中，许多患者都对1期临床试验的个人临床获益抱有很高的期望。在导致该提案的项目（RO1CAIOO77I）中，研究人员检查了当患者报告高期望获益时的含义，以及这些报告是否反映了对I期试验的了解不足。使用混合方法，研究人员确定了真正理解高期望对每个患者意味着什么的能力的几个限制。在继续他们的工作中，研究人员建议从不同的角度评估高期望获益的伦理意义。具体而言，研究人员建议在I期试验中解决高期望获益是否对患者有害的问题。许多患者在I期临床试验中没有良好的临床结果。决策影响理论预测，对获益期望较高的患者可能会对自己的参与感到更大的痛苦和负面情绪。有很多数据可以用来确定，对利益的高期望何时反映了一种有益的应对机制，而不是一种潜在有害的否认形式。这种知识上的差距带来了严重的困难，因为没有证据可以指导临床医生和研究人员决定是鼓励还是阻止患者表达高期望。随着ROICAI 00771的续期，研究人员将收集初步数据，帮助临床医生、研究人员和负责人类受试者保护的人员了解对I期试验参与者的高期望获益的后果。研究者将通过追求3个具体目标来实现这一目标：(1)探索在经历疾病进展的I期试验参与者中获益预期与后期身心健康之间的关系。研究人员假设，更高的期望与抑郁和焦虑的增加有关，他们将探索与身体功能的联系。(2)探讨在经历疾病进展的I期试验参与者中获益预期与后来对同意过程的看法之间的关联。研究人员假设，更高的期望与更多的后悔决定参加试验有关。(3)探讨第一次疾病再评估时非进展性疾病的I期研究参与者的期望与后期经历之间的关系。研究人员将在一项前瞻性研究中实现这些目标，在患者入组1期试验后立即对患者进行结构化访谈，并在患者收到初始疾病重新评估结果后一周进行随访访谈。该研究将产生初步数据，以解决在了解肿瘤1期试验中研究参与者福利方面的一个重要空白。如果对良好结果的高信心会对临床结果不佳的患者产生负面影响，这一发现可能提示临床医生和研究人员应尽量降低患者的高期望。然而，如果高期望没有负面影响，临床医生和研究人员可能会考虑是否允许对他们同意的试验有明确理解的患者进行这种治疗乐观。

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.