The real problem with equipoise

The equipoise requirement in clinical research demands that, if patients are to be randomly assigned to one of two interventions in a clinical trial, there must be genuine doubt about which is better. This reflects the traditional view that physicians must never knowingly compromise the care of their patients, even for the sake of future patients. Equipoise has proven to be deeply problematic, especially in the Third World. Some recent critics have argued against equipoise on the grounds that clinical research is fundamentally distinct from clinical care, and thus should be governed by different norms. I argue against this "difference position," and instead take issue with the traditional, exclusively patient-centered account of physicians' obligations that equipoise presupposes. In place of this traditional view, I propose a Kantian test for the reasonable partiality that physicians should show their patients, focusing on its application in clinical research and medical education.     

Risk and Trust in Public Health: A Cautionary Tale

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.     

Resituating the principle of equipoise: justice and access to care in non-ideal conditions

The principle of equipoise traditionally is grounded in the special obligations of physician-investigators to provide research participants with optimal care. This grounding makes the principle hard to apply in contexts with limited health resources, to research that is not directed by physicians, or to nontherapeutic research. I propose a different version of the principle of equipoise that does not depend upon an appeal to the Hippocratic duties of physicians and that is designed to be applicable within a wider range of research contexts and types, including health services research and research on social interventions. I consider three examples of ethically contentious research trials conducted in three different social settings. I argue that in each case my version of the principle of equipoise provides more plausible and helpful guidance than does the traditional version of the principle.     

Rethinking Professional Ethics in the Cost-Sharing Era

Changes in healthcare financing increasingly rely upon patient cost-sharing to control escalating healthcare expenditures. These changes raise new challenges for physicians that are different from those that arose either under managed care or traditional indemnity insurance. Historically, there have been two distinct bases for arguing that physicians should not consider costs in their clinical decisions—an “aspirational ethic” that exhorts physicians to treat all patients the same regardless of their ability to pay, and an “agency ethic” that calls on physicians to be trustworthy advisors to their patients. In the setting of greater patient cost-sharing, physicians' aspiration and agency roles increasingly conflict. Satisfactorily navigating the new terrain of consumer-driven healthcare requires physicians to consider these two roles and how they can best be reconciled so as to maximize quality of care while respecting the heterogeneity of patients' financial resources and willingness to pay.     

Behavioral equipoise: a way to resolve ethical stalemates in clinical research

Randomized trials depend on clinicians feeling that they are morally justified in allowing their patients to be randomized across treatment arms. Typically such justification rides on what has been called "clinical equipoise"--when there is disagreement of opinion among the community of experts about whether one treatment is better than another, then physicians can ethically enter their patients into a clinical trial, even if individual physicians are not at equipoise. Recent debates over prominent studies, however, illustrate that controversy can be easily created rather than dispelled by trials, with many clinicians choosing not to use the proven therapy until they receive more convincing evidence of its superiority. In such situations, we propose that a new standard of equipoise be used to guide decisions about the ethical justifications for research trials--a standard of behavioral equipoise. Under behavioral equipoise, a trial is potentially justifiable if it addresses behavioral resistance to prior scientific evidence.     

Clinical Equipoise and Adaptive Clinical Trials

Ethically permissible clinical trials must not expose subjects to risks that are unreasonable in relation to anticipated benefits. In the research ethics literature, this moral requirement is typically understood in one of two different ways: (1) as requiring the existence of a state of clinical equipoise, meaning a state of honest, professional disagreement among the community of experts about the preferred treatment; or (2) as requiring an equilibrium between individual and collective ethics. It has been maintained that this second interpretation makes it mandatory to minimize the number of patients receiving the treatment that will eventually be shown to be inferior by the trial. This requirement has led to the development of adaptive trials, i.e., trials in which treatment allocation is determined by data accumulated during interim analysis. Many statisticians argue that in some circumstances—typically with potentially high benefits, as in the much discussed ECMO trial—adaptive design is the only ethically permissible experimental design. Nevertheless, some proponents of clinical equipoise argue that adaptive trials are neither ethically required nor permissible. More specifically, they argue that clinical trials using adaptive designs fail to meet the moral requirement of clinical equipoise, since these trials presuppose an epistemic state that is incompatible with a physician’s duty of care to her subjects. This paper emphasizes that the debate is to a large extent resting on an epistemological confusion. Specifically, I argue that this response conflates two different conceptions of statistical evidence (i.e., frequentist and Bayesian), and that recognizing this distinction elucidates an epistemological framework in which adaptive trials are both consistent with and recommended by the moral requirement of clinical equipoise.

     

What makes placebo-controlled trials unethical?

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.     

Concepts,Attention, and Perception

Abstract

According to the conceptualist view in the philosophy of perception, we must possess concepts for all the objects, properties and relations which feature in our perceptual experiences. In this paper, I investigate the possibility of developing an argument against the conceptualist view by appealing to the notion of attention.

In Part One, I begin by setting out an apparently promising version of such an argument, a version which appeals to a link between attention and perceptual demonstrative concept possession. In Part Two, however, I show how the conceptualist can challenge what appears to be the key premise of the argument, and I go on to describe, in Part Three, an important further difficulty which we face if we attempt to overcome this challenge in a particular way. My conclusion will be that the conceptualist's challenge to the argument is convincing and hence that the argument remains inconclusive.     

Revising,Correcting, and Transferring Genes

Abstract

The distinction between germline and somatic gene editing is fundamental to the ethics of human gene editing. Multiple conferences of scientists, ethicists, and policymakers, and multiple professional bodies, have called for moratoria on germline gene editing, and editing of human germline cells is considered to be an ethical “red line” that either never should be crossed, or should only be crossed with great caution and care. However, as research on germline gene editing has progressed, it has become clear that not all germline interventions are alike, and that these differences make a significant moral difference, when it comes to ethical questions about research, regulation, clinical application, and medical justification. In this paper, I argue that, rather than lumping all germline interventions together, we should distinguish between revising, correcting, and transferring genes, and I assess the consequences of this move for the ethics of gene editing.     

Armchair methodology and epistemological naturalism

In traditional armchair methodology, philosophers attempt to challenge a thesis of the form ‘F iff G’ or ‘F only if G’ by describing a scenario that elicits the intuition that what has been described is an F that isn’t G. If they succeed, then the judgment that there is, or could be, an F that is not G counts as good prima facie evidence against the target thesis. Moreover, if these intuitions remain compelling after further (good faith) reflection, then traditional armchair methodology takes the judgment to be serious (though not infallible) evidence against the target thesis—call it secunda facie evidence—that should not be discounted as long as those intuitions retain their force. Some philosophers, however, suggest that this methodology is incompatible with epistemological naturalism, the view that philosophical inquiry should be sensitive to empirical observations, and argue that traditional armchair methodology must deemphasize the role of intuitions in philosophical inquiry. In my view, however, this would be a mistake: as I will argue, the most effective way to promote philosophical progress is to treat intuitions as having the (prima and secunda) evidential status I’ve described. But I will also argue that philosophical inquiry can produce a theory that is sensitive to empirical observations and the growth of empirical knowledge, even if it gives intuitions the prima- and secunda-facie evidential status that traditional armchair methodology demands—and thus that traditional armchair methodology, if properly practiced, need not be abandoned by naturalists, or even (except for a few exceptions) be much revised.     

How successfully can we measure well-being through measuring happiness?

Happiness is currently the topic of a wide range of empirical research, and is increasingly becoming the focus of public policy. The interest in happiness largely stems from its connection with well-being. We care about well-being – how well our lives are going for us. If we are happy it seems that, to some extent, we must be doing well. This suggests that we may be able to successfully measure well-being through measuring happiness. The problem is that both happiness and well-being are elusive and their measurement is far from uncontroversial. What exactly does information about happiness tell us about well-being? Is there more to well-being than happiness? If so, to what extent is happiness connected to well-being? These are controversial questions, but answers to them must be given if we are to make progress in the measurement of well-being. I argue that we should view happiness as an indicator of changes in well-being. I call this the Indicator View. According to this view, someone can be doing badly yet be happy insofar as their well-being is improving (and vice versa). More precisely, the Indicator View is the view that happiness is a defeasible indicator of local changes in well-being. Thus, we can successfully measure an important aspect of well-being through measuring happiness. I argue in favour of this view on the basis of an understanding of well-being that is widely acceptable. The Indicator View, therefore, has the potential to unite divided opinion over what happiness research can tell us about well-being.     

Domestic Violence Screening in Medical and Mental Health Care Settings

ABSTRACT

Health care providers and patients agree that domestic violence presents a serious health issue that falls within the purview of medical care. The patient-physician encounter has the potential to assist domestic violence victims in considering their options of living without violence and playing a critical role in preventing future violence. Despite this possibility, many persons evaluated in the health care system do not experience the benefits of such interactions. This article reviews current research that evaluates physician, patient, and systems barriers to providing care to patients experiencing domestic violence as well as gaps in the current research and suggestions for how these barriers might be overcome. Educational initiatives, implementation of protocols, and increasing environmental cues that prompt patients and physicians to discuss domestic violence may all increase the likelihood of screening and the success of interventions.     

Adolescent Decisional Autonomy Regarding Participation in an Emergency Department Youth Violence Interview

Much attention has been given to determining whether an adolescent patient has the capacity to consent to research. This study explores the factors that influence adolescents' decisions to participate in a research study about youth violence and to determine positive or negative feelings elicited by being a research subject. The majority of subjects perceived their decision to participate to be free of coercion, and few felt badly about having participated. However, adolescents who were alone in the room during the assent process were more likely to report that they chose freely to be a research subject. This study may influence the ways physicians communicate with adolescent patients around research assent within a clinical care environment.     

Will the real Charles Fried please stand up?

In response to the preceding commentary by Jerry Menikoff in this issue of the Journal, the authors argue that Fried's central concern is not that randomized clinical trials (RCTs) are conducted without consent, but rather that various aspects of the design and conduct of RCTs are in tension with physicians' duties of personal care to their patients. Although Fried does argue that the existence of equipoise cannot justify failure to obtain consent from research subjects, informed consent by itself does not supplant ill subjects' rights to personalized judgment and care embodied in Fried's equipoise.     

Ethical implications in the allocation of scarce medical resources in Poland

The health care system in Poland is undergoing major change and it is possible that these changes could affect clinical research. Therefore, the situation of funding of health care is important for the future of medical research in this country. Some questions relevant in this field will be addressed. Since funds for health care and scientific research remain inadequate, their allocation raises moral, economic, legal and organisational dilemmas. The clinical aspects of resource allocation also include physicians’ responsibilities towards their patients. Scientific research, clinical medicine, and clinical research have a common denominator: they rely on trust. The physician should be a fiduciary of the patient as well as being a researcher for the benefit of the patient and for society. Some physicians and researchers, despite unethical conduct, escape disclosure and punishment, but decision-makers who wrongly allocate funds for health care and research are never held accountable for their actions. An earlier version of this paper was presented at a symposium, Scientific Misconduct: An International Perspective, organised by The Medical University of Warsaw, 16 November, 1998.     

The patient-physician relationship and the allocation of scarce resources: a law and economics approach

Patients with insufficient financial resources place physicians in a conflict of interest between the patients' needs and the financial interests of the physician, other patients, and society. Not only must physicians act ethically, but they must avoid liability for violating their legal duties to their patients. The traditional rules of contract and malpractice law that govern the patient-physician relationship do not provide satisfactory guidelines. Better answers are found in the rules of fiduciary law, but only with regard to direct conflicts between patients and physicians and only at the risk of reducing patient access to care. Certain types of legislative action can resolve these conflicts by altering the traditional legal rules, but care must be taken to preserve patient-physician trust, which the legal rules were designed to enhance.     

Ethically Allocating COVID-19 Drugs Via Pre-approval Access and Emergency Use Authorization

Abstract

Allocating access to unapproved COVID-19 drugs available via Pre-Approval Access pathways or Emergency Use Authorization raises unique challenges at the intersection of clinical care and research. In conditions of scarcity, prioritization approaches should minimize harm, maximize benefit, and promote fairness. To promote continued data collection, patients seeking access to unproven COVID-19 drugs should receive lower priority for allocation when they decline to participate in clinical trials, either of the requested drug or other investigational products, offering a comparable balance of risks and benefits; special attention should be paid to concerns of voluntariness and distrust. In addition, institutional treatment protocols that can contribute more robust real world data should be preferred to single patient requests for access, with priority for inclusion based on traditional clinical allocation criteria relying on available evidence. Fairness demands distribution of these protocols across a diverse range of sites, particularly those serving marginalized populations, among other protections.     

Transgender Primary Medical Care

SUMMARY

Transgender medical care involves addressing general medical conditions and those related specifically to transgender issues. This article summarizes existing research in transgender medicine and provides guidance for family physicians and nurses in adapting standard primary care protocols relating to health maintenance, acute illness, and chronic disease management to address trans-specific clinical oncerns. Trans-specific issues in physical examination, health history, interpretation of laboratory tests, vaccination, screening, and treatment are explored, and the role of the primary care provider in caring for patients undergoing hormonal or surgical change is discussed.     

Cognitive Transformation,Dementia, and the Moral Weight of Advance Directives

Abstract

Dementia patients in the moderate-late stage of the disease can, and often do, express different preferences than they did at the onset of their condition. The received view in the philosophical literature argues that advance directives which prioritize the patient’s preferences at onset ought to be given decisive moral weight in medical decision-making. Clinical practice, on the other hand, favors giving moral weight to the preferences expressed by dementia patients after onset. The purpose of this article is to show that the received view in the philosophical literature is inadequate and is out of touch with real clinical practice. I argue that having dementia is a cognitive transformative experience and that preference changes which result from this are legitimate and ought to be given moral weight in medical decision-making. This argument ought to encourage us to reduce our confidence in the moral weight of advance directives for dementia patients.     

Know-how,intellectualism, and memory systems

ABSTRACT

A longstanding tradition in philosophy distinguishes between knowthatand know-how. This traditional “anti-intellectualist” view is soentrenched in folk psychology that it is often invoked in supportof an allegedly equivalent distinction between explicit and implicitmemory, derived from the so-called “standard model of memory.”In the last two decades, the received philosophical view has beenchallenged by an “intellectualist” view of know-how. Surprisingly, defenders of the anti-intellectualist view have turned to the cognitivescience of memory, and to the standard model in particular, todefend their view. Here, I argue that this strategy is a mistake. As it turns out, upon closer scrutiny, the evidence from cognitivepsychology and neuroscience of memory does not support theanti-intellectualist approach, mainly because the standard modelof memory is likely wrong. However, this need not be interpretedas good news for the intellectualist, for it is not clear that theempirical evidence necessarily supports their view either. I arguethat, currently, the philosophical debate is couched in terms thatdo not correspond to categories in psychological science. As aresult, the debate has to either be re-interpreted in a vocabularythat is amenable to experimental scrutiny, or it cannot be settledempirically.