Franklin Miller

The doctrine of clinical equipoise is appealing because it appears to permit physicians to maintain their therapeutic obligation to offer optimal medical care to patients while conducting randomized controlled trials (RCTs). The appearance, however, is deceptive. In this article we argue that clinical equipoise is defective and incoherent in multiple ways. First, it conflates the sound methodological principle that RCTs should begin with an honest null hypothesis with the questionable ethical norm that participants in these trials should never be randomized to an intervention known to be inferior to standard treatment. Second, the claim that RCTs preserve the therapeutic obligation of physicians misrepresents the patient-centered orientation of medical care. Third, the appeal to clinical equipoise as a basic principle of risk-benefit assessment for RCTs is incoherent. Finally, the difficulties with clinical equipoise cannot be resolved by viewing it as a presumptive principle subject to exceptions. In the final sections of the article, we elaborate on the non-exploitation framework for the ethics clinical research and indicate issues that warrant further inquiry.

In the research ethics literature, there is strong disagreement about the ethical acceptability of placebo-controlled trials, particularly when a tested therapy aims to alleviate a condition for which standard treatment exists. Recently, this disagreement has given rise to debate over the moral appropriateness of the principle of clinical equipoise for medical research. Underlying these debates are two fundamentally different visions of the moral obligations that investigators owe their subjects.Some commentators and ethics documents claim that physicians, whether acting as care givers or researchers, have the same duty of beneficence towards their patients and subjects: namely, that they must provide optimal medical care. In discussing placebo surgery in research on refractory Parkinson's disease, Peter Clark succinctly states this view: “The researcher has an ethical responsibility to act in the best interest of subjects.”

We seek to change the conversation about brain death by highlighting the distinction between brain death as a biological concept versus brain death as a legal status. The fact that brain death does not cohere with any biologically plausible definition of death has been known for decades. Nevertheless, this fact has not threatened the acceptance of brain death as a legal status that permits individuals to be treated as if they are dead. The similarities between “legally dead” and “legally blind” demonstrate how we may legitimately choose bright-line legal definitions that do not cohere with biological reality. Not only does this distinction bring conceptual coherence to the conversation about brain death, but it has practical implications as well. Once brain death is recognized as a social construction not grounded in biological reality, we create the possibility of changing the social construction in ways that may better serve both organ donors and recipients alike.

The view that research with competent adults requires valid consent to be ethical perhaps finds its clearest expression in the Nuremberg Code, whose famous first principle asserts that “the voluntary consent of the human subject is absolutely essential.” In a similar vein, the United Nations International Covenant on Civil and Political Rights states that “no one shall be subjected without his free consent to medical or scientific experimentation.” Yet although some formulations of the consent principle allow no exceptions, others hold that informed consent is not always strictly necessary for ethical research. The U.S. federal regulations known as the “Common Rule,” which govern research with human subjects, lists several conditions for waiving consent. However, neither guidance documents on the ethics of clinical research nor the literature in bioethics contains a general justification of research without consent. The purpose of this paper is to advance a justificatory framework that will explain why research without consent is permissible in paradigmatic cases and that can be useful in analyzing cases about which there is disagreement. We argue that research without consent can be justified on two grounds: if it stands to infringe no right of the participants and obtaining consent is impracticable, or if the gravity of the rights infringement is minor and outweighed by the expected social value of the research and obtaining consent is impracticable

Conventional medical ethics and the law draw a bright line distinguishing the permitted practice of withdrawing life-sustaining treatment from the forbidden practice of active euthanasia by means of a lethal injection. When clinicians justifiably withdraw life-sustaining treatment, they allow patients to die but do not cause, intend, or have moral responsibility for, the patient's death. In contrast, physicians unjustifiably kill patients whenever they intentionally administer a lethal dose of medication. We argue that the differential moral assessment of these two practices is based on a series of moral fictions – motivated false beliefs that erroneously characterize withdrawing life-sustaining treatment in order to bring accepted end-of-life practices in line with the prevailing moral norm that doctors must never kill patients. When these moral fictions are exposed, it becomes apparent that conventional medical ethics relating to end-of-life decisions is radically mistaken

It has been presumed within bioethics that the benefits and risks of treatments can be assessed independently of information disclosure to patients as part of the informed consent process. Research on placebo and nocebo effects indicates that this is not true for symptomatic treatments. The benefits and risks that patients experience from symptomatic treatments can be shaped powerfully by information about these treatments provided by clinicians. In this paper we discuss the implications of placebo and nocebo research for risk–benefit assessment and informed consent

: The "difference position" holds that clinical research and therapeutic medical practice are sufficiently distinct activities to require different ethical rules and principles. The "similarity position" holds instead that clinical investigators ought to be bound by the same fundamental principles that govern therapeutic medicine—specifically, a duty to provide the optimal therapeutic benefit to each patient or subject. Some defenders of the similarity position defend it because of the overlap between the role of attending physician and the role of investigator in a research trial. This overlap is maximal when the same physician occupies both roles with respect to a particular patient-subject. We address the ethical tensions inherent in that role conflict and argue that the tensions are real but manageable. The difference position provides a sound ethical framework within which to manage those tensions, while the similarity position is unsatisfactory because it seeks to deny the existence of the tensions.