Diversity of practice is widely recognized as crucial to scientific progress. If all scientists perform the same tests in their research, they might miss important insights that other tests would yield. If all scientists adhere to the same theories, they might fail to explore other options which, in turn, might be superior. But the mechanisms that lead to this sort of diversity can also generate epistemic harms when scientific communities fail to reach swift consensus on successful theories. In this paper, (...) we draw on extant literature using network models to investigate diversity in science. We evaluate different mechanisms from the modeling literature that can promote transient diversity of practice, keeping in mind ethical and practical constraints posed by real epistemic communities. We ask: what are the best ways to promote an appropriate amount of diversity of practice in scientific communities? (shrink)

Clinical equipoise has been proposed as an ethical principle relating uncertainty and moral leeway in clinical research. Although CE has traditionally been indicated as a necessary condition for a morally justified introduction of a new RCT, questions related to the interpretation of this principle remain woefully open. Recent proposals to rehabilitate CE have divided the bioethical community on its ethical merits. This paper presents a new argument that brings out the epistemological difficulties we encounter in justifying CE as a principle (...) to connect uncertainty and moral leeway in clinical ethics. The argument proposes, first, that the methodology of hypothetical retrospection is applicable to the RCT design and that it can accommodate uncertainty. As currently understood, however, HR should give up its reliance on the assumption of uncertainty transduction, because the latter assumes the principle of indifference, which does not accommodate uncertainty in the right way. The same principle is then seen to distort also the received interpretations of CE. (shrink)

The Belmont Report’s distinction between research and the practice of accepted therapy has led various authors to suggest that these purportedly distinct activities should be governed by different ethical principles. We consider some of the ethical consequences of attempts to separate the two and conclude that separation fails along ontological, ethical, and epistemological dimensions. Clinical practice and clinical research, as with yin and yang, can be thought of as complementary forces interacting to form a dynamic system in which the whole (...) exceeds the sum of its parts. Just as effective clinical practice cannot exist without clinical research, meaningful clinical research requires the context of clinical practice. We defend this thesis by triangulation, that is, by outlining how multiple investigators have reached this conclusion on the basis of varied theoretical and applied approaches. More confidence can be placed in a result if different methods/viewpoints have led to that result. (shrink)

In times of crises, public health leaders may claim that trials of public health interventions are unethical. One reason for this claim can be that equipoise—i.e. a situation of uncertainty and/or disagreement among experts about the evidence regarding an intervention—has been disturbed by a change of collective expert views. Some might claim that equipoise is disturbed if the majority of experts believe that emergency public health interventions are likely to be more beneficial than harmful. However, such beliefs are not always (...) justified: where high quality research has not been conducted, there is often considerable residual uncertainty about whether interventions offer net benefits. In this essay we argue that high-quality research, namely by means of well-designed randomized trials, is ethically obligatory before, during, and after implementing policies in public health emergencies (PHEs). We contend that this standard applies to both pharmaceutical and non-pharmaceutical interventions, and we elaborate an account of equipoise that captures key features of debates in the recent pandemic. We build our case by analyzing research strategies employed during the COVID-19 pandemic regarding drugs, vaccines, and non-pharmaceutical interventions; and by providing responses to possible objections. Finally, we propose a public health policy reform: whenever a policy implemented during a PHE is not grounded in high-quality evidence that expected benefits outweigh harms, there should be a planned approach to generate high-quality evidence, with review of emerging data at preset time points. These preset timepoints guarantee that policymakers pause to review emerging evidence and consider ceasing ineffective or even harmful policies, thereby improving transparency and accountability, as well as permitting the redirection of resources to more effective or beneficial interventions. (shrink)

From the earliest application of modern randomized controlled trials in medical research, scientists and observers have deliberated the ethics of randomly allocating study participants to trial control arms. Adaptive RCT designs have been promoted as ethically advantageous over conventional RCTs because they reduce the allocation of subjects to what appear to be inferior treatments. Critical assessment of this claim is important, as adaptive designs are changing medical research, with the potential to significantly shift how clinical trials are conducted. Policy-makers are (...) swiftly moving to encourage greater use of adaptive designs. In 2016, the newly enacted 21st Century Cures Act instructed the Food and Drug Administration to help product sponsors incorporate adaptive methods into proposed clinical trial protocols and applications for investigational drugs and also biological products. In this article, we review the ethical justifications commonly offered for adaptive designs, explore these arguments in the context of actual trials, and contend that clinical equipoise is a useful standard for adaptive-trial ethics. We distinguish between theoretical and clinical equipoise and explain why ethical arguments related to adaptive trials tend to focus on the former. Yet we contend that theoretical equipoise can be an unreliable standard for adaptive ethics. While we contend that clinical equipoise is the most critical principle for the primary ethical concerns posed by adaptive trials, we suggest ethical approaches to deal with some additional concerns unique to adaptive designs. (shrink)

The use of charged-particle radiation therapy is an increasingly important development in the treatment of cancer. One of the most pressing controversies about the use of this technology is whether randomised controlled trials are required before this form of treatment can be considered to be the treatment of choice for a wide range of indications. Equipoise is the key ethical concept in determining which research studies are justified. However, there is a good deal of disagreement about how this concept is (...) best understood and applied in the specific case of CPRT. This report is a position statement on these controversies that arises out of a workshop held at Wolfson College, Oxford in August 2011. The workshop brought together international leaders in the relevant fields , including proponents on both sides of the debate, in order to make significant progress on the ethical issues associated with CPRT research. This position statement provides an ethical platform for future research and should enable further work to be done in developing international coordinated programmes of research. (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)

In “The Real Problem With Equipoise,” Chiong (2006) raises two distinct, but interrelated issues concerning the concept of equipoise. The first deals with the role of equipoise in evaluating intern...

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)

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)

The concept of clinical equipoise restricts the use of placebo controls in clinical trials when there already exists a proven effective treatment. Several critics of clinical equipoise have put forward alleged counter-examples to this restriction—describing instances of ethical placebo-controlled trials that apparently violate clinical equipoise. In this essay, we respond to these examples and show that clinical equipoise is not as restrictive of placebos as these authors assume. We argue that a subtler appreciation for clinical equipoise—in particular the distinction between (...) de facto and de jure interpretations of the concept—allows the concept to explain when and why a placebo control may be necessary to answer a question of clinical importance. (shrink)

Doernberg and Truog (2023) present a thoughtful analysis of the ethical tensions that arise from physicians increasingly occupying “multiple roles in healthcare”1 I take no issue with the classific...

Pediatric oncology has a strong research culture. Most pediatric oncologists are investigators, involved in clinical care as well as research. As a result, a remarkable proportion of children with cancer enrolls in a trial during treatment. This paper discusses the ethical consequences of the unprecedented integration of research and care in pediatric oncology from the perspective of parents and physicians. An empirical ethical approach, combining (1) a narrative review of (primarily) qualitative studies on parents' and physicians' experiences of the pediatric (...) oncology research practice, and (2) comparison of these experiences with existing theoretical ethical concepts about (pediatric) research. The use of empirical evidence enriches these concepts by taking into account the peculiarities that ethical challenges pose in practice. Analysis of the 22 studies reviewed revealed that the integration of research and care has consequences for the informed consent process, the promotion of the child's best interests, and the role of the physician (doctor vs. scientist). True consent to research is difficult to achieve due to the complexity of research protocols, emotional stress and parents' dependency on their child's physician. Parents' role is to promote their child's best interests, also when they are asked to consider enrolling their child in a trial. Parents are almost never in equipoise on trial participation, which leaves them with the agonizing situation of wanting to do what is best for their child, while being fearful of making the wrong decision. Furthermore, a therapeutic misconception endangers correct assessment of participation, making parents inaccurately attribute therapeutic intent to research procedures. Physicians prefer the perspective of a therapist over a researcher. Consequently they may truly believe that in the research setting they promote the child's best interests, which maintains the existence of a therapeutic misconception between them and parents. Due to the integration of research and care, their different ethical perspectives become intertwined in the daily practice of pediatric oncology. Increasing awareness of what this means for the communication between parents and physicians is essential. Future research should focus on efforts that overcome the problems that the synchronicity of research and care evokes. (shrink)

With their target article, “Spheres of Morality…,” Dornberg and Truog (2023) have given us a careful analytic framework for distinguishing moral concerns among different domains involved in medical...

To give substance to the rhetoric of ‘learning health systems’, a variety of novel trial designs are being explored to more seamlessly integrate research with medical practice, reduce study duration and reduce the number of participants allocated to ineffective interventions. Many of these designs rely on response adaptive randomisation. However, critics charge that RAR is unethical on the grounds that it violates the principle of equipoise. In this paper, I reconstruct critiques of RAR as holding that it is inconsistent with (...) five important ethical principles. I then argue that these criticisms rest on a faulty view of equipoise encouraged by the idea that a RAR study models the beliefs of a single rational agent about the relative merits of the interventions being studied. I outline a view in which RAR models an idealised health system in which diverse communities of fully informed experts shrink or grow as their constituent members update their expert opinions in light of reliable medical evidence. I show how a proper understanding of clinical equipoise can reconcile this conception of RAR with these five ethical principles. This analysis removes an in-principle objection to RAR and sheds important light on the relationship between clinical equipoise and transient diversity in the scientific community. (shrink)

In the target article, Brendel and Miller (2008) attempt to bring pragmatic insights to bear on research ethics through the approach called freestanding pragmatism that John Arras (2001) brought sq...

Background Pediatric oncology has a strong research culture. Most pediatric oncologists are investigators, involved in clinical care as well as research. As a result, a remarkable proportion of children with cancer enrolls in a trial during treatment. This paper discusses the ethical consequences of the unprecedented integration of research and care in pediatric oncology from the perspective of parents and physicians. Methodology An empirical ethical approach, combining a narrative review of qualitative studies on parents' and physicians' experiences of the pediatric (...) oncology research practice, and comparison of these experiences with existing theoretical ethical concepts about research. The use of empirical evidence enriches these concepts by taking into account the peculiarities that ethical challenges pose in practice. Results Analysis of the 22 studies reviewed revealed that the integration of research and care has consequences for the informed consent process, the promotion of the child's best interests, and the role of the physician. True consent to research is difficult to achieve due to the complexity of research protocols, emotional stress and parents' dependency on their child's physician. Parents' role is to promote their child's best interests, also when they are asked to consider enrolling their child in a trial. Parents are almost never in equipoise on trial participation, which leaves them with the agonizing situation of wanting to do what is best for their child, while being fearful of making the wrong decision. Furthermore, a therapeutic misconception endangers correct assessment of participation, making parents inaccurately attribute therapeutic intent to research procedures. Physicians prefer the perspective of a therapist over a researcher. Consequently they may truly believe that in the research setting they promote the child's best interests, which maintains the existence of a therapeutic misconception between them and parents. Conclusion Due to the integration of research and care, their different ethical perspectives become intertwined in the daily practice of pediatric oncology. Increasing awareness of what this means for the communication between parents and physicians is essential. Future research should focus on efforts that overcome the problems that the synchronicity of research and care evokes. (shrink)