Preventing exploitation in human subjects research requires a benchmark of fairness against which to judge the distribution of the benefits and burdens of a trial. This paper proposes the ideal market and its fair market price as a criterion of fairness. The ideal market approach is not new to discussions about exploitation, so this paper reviews Wertheimer's inchoate presentation of the ideal market as a principle of fairness, attempt of Emanuel and colleagues to apply the ideal market to human subjects (...) research, and Ballantyne's criticisms of both the ideal market and the resulting benchmark of fairness. It argues that the criticism of this particular benchmark is on point, but the rejection of the ideal market is mistaken. After presenting a complete account of the ideal market, this paper proposes a new method for applying the ideal market to human subjects research and illustrates the proposal by considering a sample case. (shrink)

Bioethics journals have lagged behind medical and science journals in exploring the threat of conflict of interest (COI) to the integrity of publications. Some recent discussions of COI that have occurred in the bioethics literature are reviewed. Discussions of what has been termed the ?Healy affair? unintentionally demonstrate that the direct and indirect influence of undisclosed COI may come from those who call for protection from the undue influence of industry. Paradoxically, the nature and tone of current discussions may serve (...) to dull sensitivities to what is indeed a serious set of issues facing bioethics. Some proposals are presented to address COI and other challenges to the integrity of bioethics and its journals. COI is too important a topic to be left to ideologues, and there is no substitute for readers' caution and skepticism as tools in dealing with the full range of biases that exist in published papers. (shrink)

A resilient issue in research ethics is whether and when a placebo-controlled trial is justified if it deprives research subjects of a recognized treatment. The clinicians' moral duty to provide the best available care seems to require the use of ‘active’ controlled trials that use an established treatment as a control whenever such a therapy is available. In another regard, ACTs are supposedly methodologically inferior to PCTs. Hence, the moral duty of the clinical researcher to use the best methods will (...) favor PCTs. In this target article, I analyze the three reasons for believing that ACTs are inferior to PCTs namely: 1) ACTs lack ‘assay sensitivity’; 2) ACTs do not measure absolute effect size; and 3) ACTs require more participants; and I contend that none are acceptable. Consequently the tension between clinical and research ethics dissolves: the moral duty of the clinician to avoid PCTs is unopposed by methodological considerations. (shrink)

The use of placebo as a control condition in clinical trials of major depressive disorder and anxiety disorders continues to be an area of ethical concern. Typically, opponents of placebo controls argue that they violate the beneficent-based, “best proven diagnostic and therapeutic method” that the original Helsinki Declaration of 1964 famously asserted participants are owed. A more consequentialist, oppositional argument is that participants receiving placebo might suffer enormously by being deprived of their usual medication(s). Nevertheless, recent findings of potential for (...) suicidality in young people treated with antidepressants, along with meta-analyses suggesting that antidepressants add no significant clinical benefit over placebos, warrant a re-evaluation of the arguments against placebo. Furthermore, the nature of placebo treatment in short-term clinical trials is often not well understood, and lack of understanding can foster opposition to it. This paper will show how scientific justifications for placebo use are morally relevant. The fundamental ethical importance of placebo controls is discussed in relation to several aspects of clinical trials, including detection of adverse events, accurate assessment of clinical benefit, advancing understanding of the heterogeneity of depression and anxiety disorders and respecting informed consent requirements. Prohibiting the use of placebo controls is morally concerning in that such prohibitions allow for the possibility of serious adverse public health consequences. Moral worries that research participants receiving placebo are being unduly jeopardised will be shown to be exaggerated, especially in relation to the net benefits for end-users to be gained from the quality of data resulting from using placebo controls. (shrink)

Contemporary research ethics policies started with reflection on the atrocities perpetrated upoconcentration camp inmates by Nazi doctors. Apparently, as a consequence of that experience, the policies that now guide human subject research focus on the protection of human subjects by making informed consent the centerpiece of regulatory attention. I take the choice of context for policy design, the initial prioritization of informed consent, and several associated conceptual missteps, to have set research ethics off in the wrong direction. The aim of (...) this paper is to sort out these confusions and their implications and to offer instead a straightforward framework for considering the ethical conduct of human subject research. In the course of this discussion I clarify different senses of autonomy that have been confounded and present more intelligible justifications for informed consent. I also take issue with several of the now accepted dogmas that govern research ethics. These include: the primacy of informed consent, the protection of the vulnerable, the substitution of beneficence for research's social purpose, and the introduction of an untenable distinction between innovation and research. (shrink)

(2002). Therapeutic Beneficence and Patient Recruitment in Randomized Controlled Clinical Trials. The American Journal of Bioethics: Vol. 2, No. 2, pp. 35-36.

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)

Over the past several years, the most widely publicized issue in capital litigation has been the constitutional status of states’ lethal injection protocols. Death row inmates have not challenged the constitutionality of lethal injection itself, but rather execution protocols and their potential for maladministration. The inmates’ concern is due to the three-drug protocol used in the vast majority of capital jurisdictions: if the anesthetic, which is administered first, is ineffectively delivered, then the second and third drugs — the paralytic and (...) heartbeat-ceasing agents — will cause torturous pain and suffering in violation of the Eight Amendment. Inmates have argued that the participation of anesthesiologists or other highly trained medical professionals is constitutionally required to minimize the risk of unnecessary suffering. This litigation, in conjunction with evidence that some executed inmates suffered torturous pain, has reinvigorated the ethical debate about physician participation in executions. Even though the United States Supreme Court has signaled that physician participation is not constitutionally required, lawmakers in death penalty states must consider the ethics of physician involvement. (shrink)

The main public health advantages of examining gene by environment interactions in externalizing behavior lie in the realm of personalized interventions. Nevertheless, the incorporation of genetic data in randomized controlled trials is fraught with difficulties and raises ethical questions. This paper has been written from the perspective of developmental psychologists who, as researchers, see themselves confronted with important and in part new kinds of ethical questions arising from G × E research in social sciences. The aim is to explicate and (...) discuss ethical questions, based on the conviction that what is ethically salient in a research setting will also be relevant in that area of public healthcare incorporating research findings. The ethical questions discussed include: whether it is ethically responsible to withhold an effective treatment; to what extent genetic results should be disclosed; whether researchers should be allowed to collect genetic data of both child and parent; and what are costs and benefits of personalized interventions based on screening. We made an attempt to address these questions, but it is up to researchers to determine whether the solutions are suitable for their G × E research in social sciences. (shrink)

Contemporary research ethics policies started with reflection on the atrocities perpetrated upoconcentration camp inmates by Nazi doctors. Apparently, as a consequence of that experience, the policies that now guide human subject research focus on the protection of human subjects by making informed consent the centerpiece of regulatory attention. I take the choice of context for policy design, the initial prioritization of informed consent, and several associated conceptual missteps, to have set research ethics off in the wrong direction. The aim of (...) this paper is to sort out these confusions and their implications and to offer instead a straightforward framework for considering the ethical conduct of human subject research. In the course of this discussion I clarify different senses of autonomy that have been confounded and present more intelligible justifications for informed consent. I also take issue with several of the now accepted dogmas that govern research ethics. These include: the primacy of informed consent, the protection of the vulnerable, the substitution of beneficence for research's social purpose, and the introduction of an untenable distinction between innovation and research. (shrink)

The impression one derives from the target article on “The Duty to Disclose Adverse Clinical Trials Results” is that Liao and colleagues (2009) envision a research platform consisting only of a tea...

Surveys and routine clinical procedures applied in research protocols are typically considered only minimally risky to participants. The apparent benign nature of "minimal risk" tasks increases the chance that investigators and Institutional Review Boards (IRBs) will overlook the probability that clinical tools will identify signs, symptoms, or definitive test results that are clinically-relevant to subjects' welfare. "Minimal risk" procedures may also pose a particular hazard to participants in clinical research by increasing the therapeutic misconception because the tasks mimic clinical care (...) and are often conducted in clinical settings. Investigators should anticipate which measures could yield clinically-important findings and should describe explicit plans for data monitoring, disclosure, and follow-up. Protocols that include reliable and valid clinical measures should prompt a more detailed risk assessment by the IRB, even when the tasks meet the regulatory criteria for minimal physical, psychological, or emotional risk. (shrink)

BackgroundThe nature of the relationship between a clinical investigator and a research subject has generated considerable debate because the investigator occupies two distinct roles: clinician and scientist. As a clinician, the investigator has duties to provide the patient with optimal care and undivided loyalty. As a scientist, the investigator has duties to follow the rules, procedures and methods described in the protocol.Results and conclusionIn this article, I present a contextual approach to the investigator-subject relationship. The extent of the investigator's duty (...) to provide the patient/subject with clinical care can vary from one situation to the next, as a function of several factors, including: the research design, benefits and risks of the research; the subject's reasonable expectations, motivations, and vulnerabilities; the investigator's ability to benefit the subject; and the investigator's prior relationship with the subject. These and other factors need to be considered when determining the clinical investigator's obligations to provide clinical care to human research subjects. In some research contexts, the investigator has extensive clinical obligations to the patient/subject; in others, the investigator has minimal ones. (shrink)

(2002). Avoiding a Jekyll-And-Hyde Approach to the Ethics of Clinical Research and Practice. The American Journal of Bioethics: Vol. 2, No. 2, pp. 14-17.

The Belmont Report was written by a US Commission charged by the US Congress to advise on research supported by the US government. Its focus was understandably domestic. In the 40 years since its publication, clinical research has become increasingly international. Many clinical trials have sites in multiple countries, and many of the host countries are relatively impoverished. Such research raises some distinctive ethical issues. This paper outlines some of the key ethical challenges that have been raised by clinical research (...) conducted in low- and middle-income countries (LMICs) and sponsored by high-income country (HIC) institutions. It then considers whether the Belmont Report has the resources to address these problems and argues that it does not. The article closes by noting some parallels between this international research and domestic US research, which suggest that the US might benefit from the discussions abroad. (shrink)

In October 2013, the Declaration of Helsinki was revised a seventh time in its 50 year history. While it is the most widely accepted set of ethical principles for the protection of patients participating in medical research, the Declaration of Helsinki has also been subject of constant controversy. In particular, its paragraph on the use of placebo controls in clinical trials divides the research community into active-control and placebo orthodox proponents, both continuously demanding revisions of the Declaration of Helsinki in (...) favour of their position. The goal of the present project is to compare the mainly theoretical controversy with regulatory implementation. We distributed a questionnaire to national drug regulatory authorities from different countries to collect information on the authorities’ respective approaches to interpretation and implementation of the Declarations’ placebo paragraph in the conduct of medical research. Our findings suggest that the majority of drug regulatory authorities have established a practice of a middle ground, allowing placebo controls in some instances. Various interpretations of “serious harm” and “methodological reasons” are proposed as well as safeguards to avoid abuse of the option to use placebo-controls. Leaving the placebo paragraph open to various interpretation is a result of the Declaration of Helsinki’s character as a guidance document. With the current version controversy will continue. The Declaration should be continued to be strengthened to enforce the appreciation of conducting medical research with the highest ethical standard. (shrink)

Surgical clinical trials have seldom used a "sham" or placebo surgical procedure as a control, owing to ethical concerns. Recently, several ethical commentators have argued that sham surgery is either inherently or presumptively unethical. In this article I contend that these arguments are mistaken and that there are no sound ethical reasons for an absolute prohibition of sham surgery in clinical trials. Reflecting on three cases of sham surgery, especially on the recently reported results of a sham-controlled trial of arthroscopic (...) surgery for arthritis of the knee, I present an ethical analysis that focuses on the methodological rationale for use of sham surgery, risk-benefit assessment, and informed consent. (shrink)

Contemporary research ethics policies started with reflection on the atrocities perpetrated upon concentration camp inmates by Nazi doctors. Apparently, as a consequence of that experience, the policies that now guide human subject research focus on the protection of human subjects by making informed consent the centerpiece of regulatory attention. I take the choice of context for policy design, the initial prioritization of informed consent, and several associated conceptual missteps, to have set research ethics off in the wrong direction. The aim (...) of this paper is to sort out these confusions and their implications and to offer instead a straightforward framework for considering the ethical conduct of human subject research. In the course of this discussion I clarify different senses of autonomy that have been confounded and present more intelligible justifications for informed consent. I also take issue with several of the now accepted dogmas that govern research ethics. These include: the primacy of informed consent, the protection of the vulnerable, the substitution of beneficence for research's social purpose, and the introduction of an untenable distinction between innovation and research. (shrink)

This thesis analyses the use of 'Evidence-Based' methodologies of evidence assessment and intervention and policy design from medicine, and their use in sport and exercise science. It argues that problems exist with the application of Evidence-Based methodologies in sports science, meaning that the quality of evidence used to inform decision-making is lower than is often assumed. This thesis also offers realistic solutions to these problems, broadly arguing for the importance of taking evidence from mechanistic studies seriously, in addition to evidence (...) from RCTs. (shrink)

Surgical clinical trials have seldom used a “sham” or placebo surgical procedure as a control, owing to ethical concerns. Recently, several ethical commentators have argued that sham surgery is either inherently or presumptively unethical. In this article I contend that these arguments are mistaken, and that there are no sound ethical reasons for an absolute prohibition of sham surgery in clinical trials. Reflecting on three cases of sham surgery, especially on the recently reported results of a sham-controlled trial of arthroscopic (...) surgery for arthritis of the knee, I present an ethical analysis that focuses on the methodological rationale for use of sham surgery, risk-benefit assessment, and informed consent. (shrink)

Given that health systems research involves different aims, approaches, and methodologies as compared to more traditional clinical trials, the ethical issues present in HSR may be unique or particularly nuanced. This article outlines eight pertinent ethical issues that are particularly salient in HSR and argues that the ethical review process should be better tailored to ensure more efficient and appropriate oversight of HSR with adequate human protections, especially in low- and middle-income countries. The eight ethical areas we discuss include the (...) nature of intervention, types of research subjects, units of intervention and observation, informed consent, controls and comparisons, risk assessment, inclusion of vulnerable groups, and benefits of research. HSR involving human participants is necessary to ensure health systems strengthening and quality of care and to guide public policy intelligently. Health systems researchers must carefully define their intent and goals and openly clarify the values that may influence the premises and design of protocols. As new types of population-level research activities become more commonplace, it is critical that institutional review board and research ethics committee review processes evolve to evaluate these research protocols in ways that address the nuanced features of these studies. (shrink)

Drawing on an analysis of Irving Kirsch and colleagues’ controversial 2008 article in PLoS [Public Library of Science] Medicine on the efficacy of SSRI antidepressant drugs such as Prozac, I examine flaws within the methodologies of randomized controlled trials (RCTs) that have made it difficult for regulators, clinicians and patients to determine the therapeutic value of this class of drug. I then argue, drawing analogies to work by Pierre Bourdieu and Michael Power, that it is the very limitations of RCTs (...) — their inadequacies in producing reliable evidence of clinical effects — that help to strengthen assumptions of their superiority as methodological tools. Finally, I suggest that the case of RCTs helps to explore the question of why failure is often useful in consolidating the authority of those who have presided over that failure, and why systems widely recognized to be ineffective tend to assume greater authority at the very moment when people speak of their malfunction. (shrink)

During the past decennium, one of the main issues discussed in research ethics has been focused on the care that should be provided to the control group in a clinical trial. This discussion is also called the standard of care debate . Current international research ethics guidelines contain a wide variety of standards for the standard of care—including the provision of the highest attainable, the best available, the best current, a proven , and an established effective treatment. In this article, (...) we systematically review the currently used standards and argue that none of the current standards is adequate to serve as a universal standard for the standard of care. Alex London has made a substantial proposal for a universal standard, but universally adopting his standard is problematic. In this article, we propose a revised version of London's standard. (shrink)

(2002). Clinical Research Should Not Be Permitted to Escape the Ethical Orbit of Clinical Care. The American Journal of Bioethics: Vol. 2, No. 2, pp. 27-28.

The conduct of clinical trials involving placebo in developing countries in the presence of an existing effective treatment triggered an intense debate on the standard of care to be provided to those populations. Charges of exploitation of vulnerable groups and double standards have been raised by several scholars. In response to these concerns, the Declaration of Helsinki was revised in 2000, 2008 and 2013, eventually endorsing the golden standard instead of the local standard of care. The European Union adopted a (...) strategy on the Marketing Authorization of medicinal products tested in third countries, improved with Regulation 536/2014 on clinical trials on medicinal products for human use. Additional rules have been enacted by other international organizations. The present paper has the aim of analyzing scope and content of existing international and regional standards on placebo. (shrink)

The Helsinki Declaration, first published in 1964, is the universally accepted standard for ethical behavior in research involving human subjects. The Declaration was formulated in response to the abuses of human subjects by the scientists in Nazi Germany and to update the Nuremberg Code. Amended in 1975, 1983, 1989, 1996, and 2000, the Declaration provides the foundation for the United States federal regulations for research involving human subjects.To conform to standards developed in the Declaration, a researcher must fulfill the following: (...) respect the autonomy of the individual; promote and safeguard the individual’s health; provide informed consent without coercion; take special measures with vulnerable populations; compare new therapies to the best current therapies; have a thorough scientific knowledge of the subject; assess risk versus benefit of the intervention; perform studies that will ultimately benefit the population involved in the research; accurately report their findings; and fully disclose ethical concerns in their research protocols. (shrink)

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. (shrink)

(2002). Clarifying the Ethics of Clinical Research: A Path toward Avoiding the Therapeutic Misconception. The American Journal of Bioethics: Vol. 2, No. 2, pp. 22-23.