Franklin Miller

Traditionally, biomedical research has been devoted to improvement in the understanding and treatment or prevention of disease. Building on the knowledge generated by the long history of disease-oriented research, the next few decades will witness an explosion of biomedical enhancements to make people faster, stronger, smarter, less forgetful, happier, prettier, and live longer (Turner et al. 2003; Vastag 2004; Rose 2002). As with other biomedical interventions, research to assess the safety and efficacy of these enhancements in humans should be conducted before their introduction into clinical practice.1 However, various concerns regarding the ethics of enhancement research could be raised. Those who ..

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

Human life and death should be defined biologically. It is important not to conflate the definition of death with the criteria for when it has occurred. What is distinctively "human" from a scientific or normative perspective has nothing to do with what makes humans alive or dead. We are biological organisms, despite the fact that what is meaningful about human life is not defined in biological terms. Consequently, as in the rest of the realm of living beings, human beings die when they no longer function biologically as organisms. In contrast, a determination of exactly when death has occurred, required to serve various social purposes, combines social and normative considerations with biological facts.

Payment to recruit research subjects is a common practice but raises ethical concerns relating to the potential for coercion or undue influence. We conducted the first national study of IRB members and human subjects protection professionals to explore attitudes as to whether and why payment of research participants constitutes coercion or undue influence. Upon critical evaluation of the cogency of ethical concerns regarding payment, as reflected in our survey results, we found expansive or inconsistent views about coercion and undue influence that may interfere with valuable research. In particular, respondents appear to believe that coercion and undue influence lie on a continuum; by contrast, we argue that they are wholly distinct: whereas undue influence is a cognitive distortion relating to assessment of risks and benefits, coercion is a threat of harm. Because payment is an offer, rather than a threat, payment is never coercive

The term therapeutic misconception was coined by Paul Appelbaum and his colleagues to describe the tendency of patients enrolled in clinical trials to confuse research participation with the personal clinical attention characteristic of medical care. It has not been recognized that an analogous therapeutic misconception pervades ethical thinking about clinical research with patient-subjects. Investigators and bioethicists often judge the ethics of clinical research based on ethical standards appropriate to the physician-patient relationship in therapeutic medicine. This ethical approach to clinical research constitutes a misconception because it fails to appreciate the ethically significant differences between clinical research and clinical care.In this article I argue that the assumption that the ethical principles governing the practice of therapeutic medicine should also apply to clinical research with patient- subjects produces incoherence in research ethics and erroneous guidance concerning certain controversial research designs.

Prevailing ethical thinking about informed consent to clinical research is characterized by theoretical confidence and practical disquiet. On the one hand, bioethicists are confident that informed consent is a fundamental norm. And, for the most part, they are confident that what makes consent to research valid is that it constitutes an autonomous authorization by the research participant. On the other hand, bioethicists are uneasy about the quality of consent in practice. One major source of this disquiet is substantial evidence of the “therapeutic misconception”—the tendency of patient-subjects in clinical trials to confuse participating in research with receiving personalized medical care. This ..

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

The practice of transplantation of vital organs from “brain-dead” donors is in a state of theoretical disarray. Although the law and prevailing medical ethics treat patients diagnosed as having irreversible total brain failure as dead, scholars have increasingly challenged the established rationale for regarding these patients as dead. To understand the ethical situation that we now face, it is helpful to revisit the writings of the philosopher Hans Jonas, who forcefully challenged the emerging effort to redefine death in the late 1960s.

Next SectionThere has been considerable debate surrounding the ethics of sham-controlled trials of procedures and interventions. Critics argue that these trials are unethical because participants assigned to the control group have no prospect of benefit from the trial, yet they are exposed to all the risks of the sham intervention. However, the placebo effect associated with sham procedures can often be substantial and has been well documented in the scientific literature. We argue that, in light of the scientific evidence supporting the benefits of sham interventions for pain and Parkinson's disease that stem from the placebo effect, these sham-controlled trials should be considered as offering potential direct benefit to participants. If scientific evidence demonstrates the positive effect of placebo from sham interventions on other conditions, sham-controlled trials of interventions for the treatment of these conditions should be considered to have prospects of benefit as well. This potential benefit should be taken into account by research ethics committees in risk-benefit analyses, and be included in informed consent documents

Although informed consent is important in clinical research, questions persist regarding when it is necessary, what it requires, and how it should be obtained. The standard view in research ethics is that the function of informed consent is to respect individual autonomy. However, consent processes are multidimensional and serve other ethical functions as well. These functions deserve particular attention when barriers to consent exist. We argue that consent serves seven ethically important and conceptually distinct functions. The first four functions pertain principally to individual participants: (1) providing transparency; (2) allowing control and authorization; (3) promoting concordance with participants' values; and (4) protecting and promoting welfare interests. Three other functions are systemic or policy focused: (5) promoting trust; (6) satisfying regulatory requirements; and (7) promoting integrity in research. Reframing consent around these functions can guide approaches to consent that are context sensitive and that maximize achievable goals.

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.

Pragmatism is a distinctive approach to clinical research ethics that can guide bioethicists and members of institutional review boards (IRBs) as they struggle to balance the competing values of promoting medical research and protecting human subjects participating in it. After defining our understanding of pragmatism in the setting of clinical research ethics, we show how a pragmatic approach can provide guidance not only for the day-to-day functioning of the IRB, but also for evaluation of policy standards, such as the one that addresses acceptable risks for healthy children in clinical research trials. We also show how pragmatic considerations might influence the debate about the use of deception in clinical research. Finally, we show how a pragmatic approach, by regarding the promotion of human research and the protection of human subjects as equally important values, helps to break down the false dichotomy between science and ethics in clinical research.

: This paper presents a method of moral problem solving in clinical practice that is inspired by the philosophy of John Dewey. This method, called "clinical pragmatism," integrates clinical and ethical decision making. Clinical pragmatism focuses on the interpersonal processes of assessment and consensus formation as well as the ethical analysis of relevant moral considerations. The steps in this method are delineated and then illustrated through a detailed case study. The implications of clinical pragmatism for the use of principles in moral problem solving are discussed.

The leading ethical position on placebo-controlled clinical trials is that whenever proven effective treatment exists for a given condition, it is unethical to test a new treatment for that condition against placebo. Invoking the principle of clinical equipoise, opponents of placebo-controlled trials in the face of proven effective treatment argue that they (1) violate the therapeutic obligation of physicians to offer optimal medical care and (2) lack both scientific and clinical merit. We contend that both of these arguments are mistaken. Clinical equipoise provides erroneous ethical guidance in the case of placebo-controlled trials, because it ignores the ethically relevant distinction between clinical trials and treatment in the context of clinical medicine and the methodological limitations of active-controlled trials. Placebo controls are ethically justifiable when they are supported by sound methodological considerations and their use does not expose research participants to excessive risks of harm.

The problem of physician-assisted death, assisted suicide and active euthanasia, has been debated predominantly in the ethically familiar vocabulary of rights, duties, and consequences. Patient autonomy and the right to die with dignity vie with the duty of physicians to heal, but not to kill, and the specter of “the slippery slope” from voluntary euthanasia as a last resort for patients suffering from terminal illness to PAD on demand and mercy killing of “hopeless” incompetent patients. Another dimension of the debate over PAD concerns the evaluative question of what constitutes a good death. At stake are Issues of character and virtue in the face of death and dying and their Implications for legitimizing the practice of PAD. Critics of PAD argue that “natural” death in the context of comfort care, as provided by hospice programs, is the good death. In contrast, PAD amounts to an easy way out, an evasion of the ultimate human challenge and task of dying. Because hospice care is clearly preferable to PAD, the former should be encouraged and the latter remain prohibited

Despite strong growth in scientific investigation of the placebo effect, understanding of this phenomenon remains deeply confused. We investigate critically seven common conceptual distinctions that impede clear understanding of the placebo effect: (1) verum/placebo, (2) active/inactive, (3) signal/noise, (4) specific/nonspecific, (5) objective/subjective, (6) disease/illness, and (7) intervention/context. We argue that some of these should be eliminated entirely, whereas others must be used with caution to avoid bias. Clearing away the conceptual underbrush is needed to lay down a path to understanding and harnessing placebo effects in clinical medicine

Transplantation of vital organs has been premised ethically and legally on "the dead donor rule" (DDR)—the requirement that donors are determined to be dead before these organs are procured. Nevertheless, scholars have argued cogently that donors of vital organs, including those diagnosed as "brain dead" and those declared dead according to cardiopulmonary criteria, are not in fact dead at the time that vital organs are being procured. In this article, we challenge the normative rationale for the DDR by rejecting the underlying premise that it is necessarily wrong for physicians to cause the death of patients and the claim that abandoning this rule would exploit vulnerable patients. We contend that it is ethical to procure vital organs from living patients sustained on life support prior to treatment withdrawal, provided that there is valid consent for both withdrawing treatment and organ donation. However, the conservatism of medical ethics and practical concerns make it doubtful that the DDR will be abandoned in the near future. This leaves the current practice of organ transplantation based on the "moral fiction" that donors are dead when vital organs are procured

A basic question of medical ethics is whether the norms governing medical practice should be understood as the application of principles and rules of the common morality to medicine or whether some of these norms are internal or proper to medicine. In this article we describe and defend an evolutionary perspective on the internal morality of medicine that is defined in terms of the goals of clinical medicine and a set of duties that constrain medical practice in pursuit of these goals. This perspective is developed by means of a critical examination of the essentialist conception of the internal morality of medicine advocated by Edmund Pellegrino and the critique of internal morality approaches by Robert Veatch and Tom Beauchamp.

Despite growing scientific interest in the placebo effect and increasing understanding of neurobiological mechanisms (Finniss et al. 2010), theoretical conceptualization of the placebo effect remains primitive (Miller, Colloca, and Kaptchuk 2009). Mechanistic research on this phenomenon appears largely free-floating, with little guidance by any systematic theoretical paradigm. A partial explanation is the pervasive conceptual confusion that characterizes thinking about the placebo effect. The philosopher of science Adolf Grunbaum noted that "the medical and psychiatric literature on placebos and their effects is conceptually bewildering, to the point of being a veritable Tower of Babel" (Grunbaum 1994, p. 286). ..

: 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

Debriefing is a standard ethical requirement for human research involving the use of deception. Little systematic attention, however, has been devoted to explaining the ethical significance of debriefing and the specific ethical functions that it serves. In this article, we develop an account of debriefing as a tool of moral accountability for the prima facie wrong of deception. Specifically, we contend that debriefing should include a responsibility to promote transparency by explaining the deception and its rationale, to provide an apology to subjects for infringing the principle of respect for persons, and to offer subjects an opportunity to withdraw their data. We also present recommendations concerning the discussion of deception in scientific articles reporting the results of research using deception.

John McMillan's article raises numerous important points about the ethics of surgical castration of sex offenders.1 In this commentary, we focus solely on and argue against the claim that the offer of release from detention conditional upon surgical castration is a coercive offer that compromises the validity of the offender's consent. We take no view on the question as to whether castration for sex offenders is ethically permissible. But, we reject the claim that it is ethically permissible only if competing ethical considerations outweigh worries about coercion. For in the situation described, the proposal is not coercive at all.McMillan states that if offenders agree to castration because they fear long-term detention, then ‘it seems, intuitively, as if agreeing to be castrated under these conditions makes the decision coerced in some way.’1 He adds that if castration is ‘the only way that they will be released back into the community, the status of this decision as a genuine expression of their autonomy is questionable.’1 In defence of his claim, he uses two analogies that he borrows from Joel Feinberg. First, if a governor offers to commute a death sentence if the prisoner agrees to participate in a medical experiment, then ‘it's clear that the governor is coercing the prisoner.’1 Second, if a millionaire offers to give a woman $1 000 000 …