Benefit in Phase 1 Oncology Trials: Therapeutic Misconception or Reasonable Treatment Option?

Department of Bioethics, Clinical Center, National Institutes of Health, Bethesda, MD 20892-1156, USA.
Clinical Trials (Impact Factor: 1.93). 02/2008; 5(6):617-23. DOI: 10.1177/1740774508097576
Source: PubMed


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.

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    • "After all, phase 1 trials evaluate drug safety, not efficacy. However, available data suggest that phase 1 drugs in oncology offer a prospect of direct clinical benefit for study participants (Miller and Joffe 2008). Thus, it would not be unreasonable for investigators to offer these drugs with therapeutic intent or warrant. "
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    • "First, it might be claimed that the relevant standard of competent care outside the study is not " no treatment. " Indeed, some commentators have argued—in the context of cancer Phase 1 trials—that the risks and benefits of study participation should be compared against the risks and benefits posed by nonvalidated anticancer agents that treatment refractory patients might receive outside a study (Miller and Joffe 2008 "
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    ABSTRACT: Notwithstanding requirements for scientific/social value and risk/benefit proportionality in major research ethics policies, there are no widely accepted standards for these judgments in Phase 1 trials. This paper examines whether the principle of clinical equipoise can be used as a standard for assessing the ratio of risk to direct-benefit presented by drugs administered in one category of Phase 1 study--first-in-human trials involving patients. On the basis of the supporting evidence for, and architecture of, Phase 1 studies, the articles offers two provisional conclusions: (1) the risks of drug administration in such trials cannot generally be justified on therapeutic grounds but by appeal to the social value of the research; and (2) a framework for adjudicating the ratio of risk/social-value must be developed.
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