Benefit in phase 1 oncology trials: therapeutic misconception or reasonable treatment option?
ABSTRACT Novel treatments for cancer are tested initially in phase 1 trials enrolling patients with advanced disease who have exhausted standard treatment options. Although these trials are designed to evaluate safety and to define dosing for future efficacy trials, most patients volunteer with the hope of obtaining medical benefit. Do phase 1 oncology trials promote a 'therapeutic misconception' among eligible patients about the personal meaning of trial participation, or do they offer them a reasonable prospect of direct medical benefit as compared with available alternatives? Recent evidence on outcomes of phase 1 oncology trials is examined systematically, with the aim of accurately assessing the prospect of direct medical benefit for participants and drawing implications for informed consent. We argue that, in view of important uncertainties, aggregate data from phase 1 trials relating to the surrogate outcomes of tumor shrinkage and stable disease do not permit any definitive estimate of a 'clinical benefit rate.' Nevertheless, these trials do offer participants a prospect of direct medical benefit. As a result, accurately informed patients may reasonably decide to enroll in phase 1 oncology trials in hopes of obtaining benefit, after considering the anticipated risks and available clinical alternatives. Motivation to enroll in these studies to receive personal benefit does not, in itself, compromise informed consent.
SourceAvailable from: Lynn A Jansen[Show abstract] [Hide abstract]
ABSTRACT: When patients enrolled in early-phase cancer treatment trials are asked later to explain their decision to participate, they often reveal unrealistically high expectations for therapeutic benefit from participation. This phenomenon has given rise to a complex and ongoing debate over the quality and validity of informed consent to these trials. Bioethicists and researchers must better understand these expectations and why research participants so often have them. This article presents a new explanation for this phenomenon by drawing on social psychology research on mindsets and, in particular, on a distinction between deliberative and implementation mindsets.The Hastings Center Report 01/2014; 44(1). DOI:10.1002/hast.237 · 1.08 Impact Factor
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ABSTRACT: In a previous study, we found that patients who were offered the possibility of participation in a clinical trial had unexpressed concerns and fears that prevented them from making free or fully knowledgeable choices about their trial participation. In a selected population of patients who were offered participation in a phase I trial, we prospectively investigated whether a face-to-face discussion about their unexpressed fears might lead to a more conscious decision about whether to accept/refuse participation in the trial. After the presentation of the trial, a questionnaire was administered to assess the presence of specific fears. Before the patients decided whether to participate in the trial, they discussed any fears that they had; finally, the impact of the discussion on the patients' choice to participate was evaluated. The majority (86%) of the patients thought that physicians conduct clinical trials for scientific interest, 13% felt exploited as 'guinea pigs' and 20% believed they were offered participation because they had no further hope for improvement. These existing fears were not elicited during the trial interview because the patients were themselves unaware of having them (28%) and because of fear of the doctors (3%). The possibility of discussing these fears was felt as an opportunity and made patients feel more conscious (92%) and freer (97%) when making their choice. Recognising and discussing misconceptions and fears, often unexpressed, make patients freer and more aware when facing the choice of whether or not \to participate in a phase I clinical trial. Copyright © 2013 John Wiley & Sons, Ltd.Psycho-Oncology 03/2014; 23(3). DOI:10.1002/pon.3424 · 4.04 Impact Factor
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ABSTRACT: ABSTRACT This article attempts to answer the following normative questions: Can one consider the design of Phase 1 trials ethically appropriate due to the unfavorable ratio of risks and benefits? What are some ethical safeguards for Phase 1 oncology research? A comparative review of literature contributed to the consolidation of the proposed ethical framework for Phase 1 oncology trials. This framework gives a special attention to issues of therapeutic misconception and vulnerability. The benefits and dangers associated with the enrollment in trials are described as well as the absence of alternatives, treatment-specific optimism, and vagueness in factual presentation during the informed consent process. The notion of therapeutic misconception is contrasted with optimism despite realism that stems from psychological, cultural, and religious factors and not necessarily from the lack of information. Close attention is given to the possible ways in which the inherent uncertainty and resulting cognitive biases may affect the informed consent process and the definition of therapeutic misconception. The article ends with recommendations for an ethical way of enrolling palliative patients in early stages of oncology research, giving special attention to provision of adequate consent, protection of vulnerability, and avoidance of therapeutic misconception.Journal of Pain & Palliative Care Pharmacotherapy 05/2014; DOI:10.3109/15360288.2014.908994