Outcome-adaptive randomization has been proposed as a corrective to certain ethical difficulties inherent in the traditional randomized clinical trial using fixed-ratio randomization. In particular, it has been suggested that OAR redresses the balance between individual and collective ethics in favour of the former. In this paper, I examine issues of welfare and autonomy arising in relation to OAR. A central issue in discussions of welfare in OAR is equipoise, and the moral status of OAR is crucially influenced by the way (...) in which this concept is construed. If OAR is based on a model of equipoise that demands strict indifference between competing interventions throughout the trial, such equipoise is disturbed by accruing data favouring one treatment over another; OAR seeks to redress this by weighting randomization to the seemingly superior treatment. However, this is a partial response, as patients continue to be allocated to the inferior therapy. Moreover, it rests upon considerations of aggregate harms and benefits, and does not therefore uphold individual ethics. Issues of fairness also arise, as early and late enrollees are randomized on a different basis. Fixed-ratio randomization represents a fuller and more consistent response to a loss of equipoise, as so construed. With regard to consent, the complexity of OAR poses challenges to adequate disclosure and comprehension. Additionally, OAR does not offer a remedy to the therapeutic misconception—participants’ tendency to attribute treatment allocation in an RCT to individual clinical judgments, rather than to scientific considerations—and, if anything, accentuates rather than alleviates this misconception. In relation to these issues, OAR fails to offer ethical advantages over fixed-ratio randomization. More broadly, the ethical basis of OAR can be seen to lie more in collective than in individual ethics, and overall it fares worse in this territory than fixed-ratio randomization. (shrink)

Psychiatric research is of critical importance in improving the care of persons with mental illness. Yet it may also raise difficult ethical issues. This article explores those issues in the context of a particular kind of research: psychosocial intervention research with control groups. We discuss 4 broad categories of ethical issues: consent, confidentiality, boundary violations, and risk-benefit issues. We believe that, despite the potential difficulties, psychosocial intervention research is vital and can be accomplished in an ethical manner. Further discussion and (...) research into these issues are warranted. (shrink)

This paper targets an orphan topic in research ethics, namely the so called principle of the primacy of the human being, which states that the interests of the human subject should always take precedence over the interests of science and society. Although the principle occupies the central position in the majority of international ethical and legal standards for biomedical research, it has been commented in the literature mainly in passing. With a few notable exceptions, there is little in-depth discussion about (...) the meaning and role of the principle. Several authors note that the principle is vogue, ambiguous and apparently conflicting with the accepted practice of conducting non-beneficial research on individuals unable to give consent. There are opinions that it is just “a vacuous figure of speech” and should be abandoned. This paper argues that the primacy principle is far from being “a vacuous figure of speech”, rather it should be seen as a threefold concept: a fundamental interpretative rule, a procedural rule, and a substantive rule aimed at protecting research subjects from instrumental treatment and unacceptable risks. This interpretation tracks back to the principle regulatory and normative origins in the Declaration of Helsinki of 1975, but also acknowledges changes in research ethics and practice, which took place at the turn on the twentieth and twenty-first centuries. Thus, the proposed reading of the principle is not only original, but also historically grounded and normatively fruitful. It provides a fresh and ethically rich perspective on extensively debated, but still controversial problem of an upper limit of permissible risks in non-beneficial studies. (shrink)

Evidence based medicine has been a topic of considerable controversy in medical and health care circles over its short lifetime, because of the claims made by its exponents about the criteria used to assess the evidence for or against the effectiveness of medical interventions. The central epistemological debates underpinning the debates about evidence based medicine are reviewed by this paper, and some areas are suggested where further work remains to be done. In particular, further work is needed on the theory (...) of evidence and inference; causation and correlation; clinical judgment and collective knowledge; the structure of medical theory; and the nature of clinical effectiveness. (shrink)

This article addresses the impact of the potential conflict between the roles of physicians who are both clinicians and researchers on the recruitment of persons into research trials. It has been proposedthat a physician breaches inter-role confidentiality when he or she uses information gathered in his or her clinical role to inform patients about trials for which they may be eligible and that clinician-researchers should adopt a model of preliminary consent to be approached about research prior to commencing a clinical (...) relationship. This article argues that even if we grant the legitimacy of inter-role confidentiality (which is open to question), there are circumstances in which other obligations physicians bear override the obligation of inter-role confidentiality. Moreover, it is argued that the practice of preliminary consent is morally suspect and that such consent cannot be deemed valid. The article concludes with a series of recommendations of ways in which the legitimate concern regarding the conflicting roles of clinician-researchers can be addressed in the recruitment stage of research. (shrink)

When evaluating an innovative intervention in a randomised controlled trial , choosing an appropriate control intervention is necessary for a clinically meaningful result. An RCT reported in 2000 addressed the relative merits of two tidal volume ventilatory strategies, 6 ml/kg and 12 ml/kg , in patients with acute respiratory distress syndrome. Critics claim that the 12 ml/kg volume did not represent the clinical practice standard at that time, and that lower tidal volumes had been used in some patients prior to (...) randomisation. The trialists responded that current practice involved the use of a broad range of tidal volumes, including 12 ml/kg. Appropriate control interventions for RCTs can be ensured by: a systematic review of the relevant literature; a formal survey of expert clinicians; and publication of the proposed research protocol to solicit critical appraisal. A global survey of experts during the RCT’s design stage would have been of probative value in determining the appropriate control tidal volume. Hypothetical, but plausible, results of such a survey are presented and examined to demonstrate the value of this method. (shrink)

A probabilistic explication is offered of equipoise and uncertainty in clinical trials. In order to be useful in the justification of clinical trials, equipoise has to be interpreted in terms of overlapping probability distributions of possible treatment outcomes, rather than point estimates representing expectation values. Uncertainty about treatment outcomes is shown to be a necessary but insufficient condition for the ethical defensibility of clinical trials. Additional requirements are proposed for the nature of that uncertainty. The indecisiveness of our criteria for (...) cautious decision-making under uncertainty creates the leeway that makes clinical trials defensible. (shrink)

Research is subject to more stringent ethical requirements than most other human activities, and a procedure that is otherwise allowed may be forbidden in research. Hence, risk-taking is more restricted in scientific research than in most non-research contexts, and privacy is better protected in scientific questionnaires than in marketing surveys. Potential arguments for this difference are scrutinized. The case in its favour appears to be weak. A stronger case can be made in favour of a difference in the opposite direction: (...) If perilous or otherwise problematic activities have to be performed it is usually better to perform them in a research context where they are properly evaluated so that guidance is obtained for the future. However, retreating from current ethical demands on research is not a desirable direction to go. Instead, research ethics can serve to inspire the introduction of more stringent ethical principles in other social sectors. (shrink)

In 2010, randomized controlled trials (RCTs) of two different biomedical strategies to prevent HIV infection had positive findings. However, despite ongoing very high levels of HIV infection in some countries and population groups, it has been made clear by regulatory authorities that the evidence remains insufficient to support either product being made available outside of research contexts in the developing world for at least two years. In addition, prevention trials in endemic areas will continue to test new interventions against placebo. (...) But the judgments of evidentiary standards are never value-neutral. Using the recent trials and their contexts as case studies, we examine the basis for these decisions, which will potentially delay access to scientific innovation to the people who are most urgently in need of it. (shrink)

Critics of clinical equipoise have long argued that it represents an overly permissive, and therefore morally unacceptable, mechanism for resolving the tensions inherent in clinical research. In particular, the equipoise requirement is often attacked on the grounds that it is not sufficiently responsive to the interests of individual patients. In this paper, we outline a view of equipoise that not only withstands a stronger version of this objection, which was recently articulated by Deborah Hellman, but also plays important roles in (...) clarifying the discussion. (shrink)

This is the first in a series of five papers on the role, remit and function of research ethics committees which are intended to provide for REC members a broad understanding of the most important issues in research ethics and governance. The first considers the rationale for having ethics review by committee at all; seeking to explain why ethics committees, as we currently have them, are so important to the wider system of governing research.

The precautionary principle holds that we should not allow scientific uncertainty to prevent us from taking precautionary measures in response to potential threats that are irreversible and potentially disastrous. Critics of the principle claim that it deters progress and development, is excessively risk-aversive and is unscientific. This paper argues that the principle can be scientific provided that the threats addressed by the principle are plausible threats, and the precautionary measures adopted are reasonable. The paper also argues that one may use (...) epistemic criteria, such as consistency, coherence and explanatory power, to determine whether a threat is plausible, and that one may use practical considerations, such as effectiveness, proportionality, cost-effectiveness, realism and consistency, to determine whether a response to a threat is reasonable. (shrink)

The principle of clinical equipoise has been variously characterized by ethicists and clinicians as fundamentally flawed, a myth, and even a moral balm. Yet, the principle continues to be treated as the de facto gold standard for conducting randomized control trials in an ethical manner. Why do we hold on to clinical equipoise, despite its shortcomings being widely known and well-advertised? This paper reviews the most important arguments criticizing clinical equipoise as well as what the most prominent proposed alternatives are. (...) In the process, it evaluates the justification for continuing to use clinical equipoise as the gold standard for randomized control trials. (shrink)

Clinical trials and other forms of evaluation of medical treatment are held to give an objective assessment of the 'clinical effectiveness' of the medical treatments under evaluation. This kind of evaluation is central to the evidence-based medicine movement, as it provides a basis for the rational selection of treatment. The ethical status of randomised clinical trials is widely agreed to depend crucially upon the state of equipoise regarding which of two treatments is more effective in a defined population. However, the (...) meaning and nature of 'clinical effectiveness' are unclear. in this paper, I discuss the proposals to define clinical effectiveness as a relational property and as an intrinsic property, and the way effectiveness may supervene upon more fundamental physical properties of treatments. I discuss whether effectiveness is a single property or a family of properties; the types of outcome which can be explained by effectiveness properties; and the relationship between 'objective' and 'preference' outcomes. This paper suggests that while it may be possible to put clinical effectiveness on a proper metaphysical footing, in practice the language of clinical effectiveness is more properly a topic of the human sciences than of the natural sciences. (shrink)

The foundations of research ethics are riven with fault lines emanating from a fear that if research is too closely connected to weighty social purposes an imperative to advance the common good through research will justify abrogating the rights and welfare of study participants. The result is an impoverished conception of the nature of research, an incomplete focus on actors who bear important moral responsibilities, and a system of ethics and oversight highly attuned to the dangers of research but largely (...) silent about threats of ineffective, inefficient, and inequitable medical practices and health systems. -/- In For the Common Good: Philosophical Foundations of Research Ethics, Alex John London defends a conception of the common good that grounds a moral imperative with two requirements. The first is to promote research that generates the information necessary to enable key social institutions to effectively, efficiently, and equitably safeguard the basic interests of individuals. The second is to ensure that research is organized as a voluntary scheme of social cooperation that respects its various contributors' moral claims to be treated as free and equal. Connecting research to the goals of a just social order grounds a framework for assessing and managing research risk that reconciles these requirements and justifies key oversight practices in non-paternalistic terms. Reconceiving research ethics as resolving coordination problems and providing credible assurance that these requirements are being met expands the issues and actors that fall within the purview of the field and provides the foundation for a more unified and coherent approach to domestic and international research. -/- This is an open access title available under the terms of a CC BY-NC-ND 4.0 license. It is free to read at Oxford Scholarship Online and offered as a free PDF download from OUP and selected open access locations. (shrink)

In robustness analysis, hypotheses are supported to the extent that a result proves robust, and a result is robust to the extent that we detect it in diverse ways. But what precise sense of diversity is at work here? In this paper, I show that the formal explications of evidential diversity most often appealed to in work on robustness – which all draw in one way or another on probabilistic independence – fail to shed light on the notion of diversity (...) relevant to robustness analysis. I close by briefly outlining a promising alternative approach inspired by Horwich’s (1982) eliminative account of evidential diversity. (shrink)