:Academic Medical Centers offer patient care and perform research. Increasingly, AMCs advertise to the public in order to garner income that can support these dual missions. In what follows, we raise concerns about the ways that advertising blurs important distinctions between them. Such blurring is detrimental to AMC efforts to fulfill critically important ethical responsibilities pertaining both to science communication and clinical research, because marketing campaigns can employ hype that weakens research integrity and contributes to therapeutic misconception and misestimation, undermining (...) the informed consent process that is essential to the ethical conduct of research. We offer ethical analysis of common advertising practices that justify these concerns. We also suggest the need for a deliberative body convened by the Association of American Medical Colleges and others to develop a set of voluntary guidelines that AMCs can use to avoid in the future, the problems found in many current AMC advertising practices. (shrink)

Novel precision oncology trial designs, such as basket and umbrella trials, are designed to test new anticancer agents in more effective and affordable ways. However, they present some ethical concerns referred to scientific validity, risk-benefit balance and informed consent. Our aim is to discuss these issues in basket and umbrella trials, giving examples of two ongoing cancer trials: NCI-MATCH (National Cancer Institute – Molecular Analysis for Therapy Choice) and Lung-MAP (Lung Cancer Master Protocol) study. We discuss three ethical requirements for (...) clinical trials which may be challenged in basket and umbrella trial designs. Firstly, we consider scientific validity. Thanks to the new trial designs, patients with rare malignancies have the opportunity to be enrolled and benefit from the trial, but due to insufficient accrual, the trial may generate clinically insignificant findings. Inadequate sample size in study arms and the use of surrogate endpoints may result in a drug approval without confirmed efficacy. Moreover, complexity, limited quality and availability of tumor samples may not only introduce bias and result in unreliable and unrepresentative findings, but also can potentially harm patients and assign them to an inappropriate therapy arm. Secondly, we refer to benefits and risks. Novel clinical trials can gain important knowledge on the variety of tumors, which can be used in future trials to develop effective therapies. However, they offer limited direct benefits to patients. All potential participants must wait about 2 weeks for the results of the genetic screening, which may be stressful and produce anxiety. The enrollment of patients whose tumors harbor multiple mutations in treatments matching a single mutation may be controversial. As to informed consent – the third requirement we discuss, the excessive use of phrases like “personalized medicine”, “tailored therapy” or “precision oncology” might be misleading and cause personal convictions that the study protocol is designed to fulfill the individual health-related needs of participants. We suggest that further approaches should be implemented to enhance scientific validity, reduce misunderstandings and risks, thus maximizing the benefits to society and to trial participants. (shrink)

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)

BackgroundAfrica continues to bear a disproportionate share of the global HIV/AIDS, tuberculosis (TB) and malaria burden. The development and distribution of safe, effective and affordable vaccines is critical to reduce these epidemics. However, conducting HIV/AIDS, TB, and/or malaria vaccine trials simultaneously in developing countries, or in populations affected by all three diseases, is likely to result in numerous ethical challenges.MethodsIn order to explore convergent ethical issues in HIV/AIDS, TB and malaria vaccine trials in Africa, the Ethics, Law and Human Rights (...) Collaborating Centre of the WHO/UNAIDS African AIDS Vaccine Programme hosted a consultation on the Convergent Ethical Issues in HIV/AIDS, TB and Malaria Vaccine Trials in Africa in Durban, South Africa on the 10-11 February 2009.ResultsKey cross cutting ethical issues were prioritized during the consultation as community engagement; ancillary care obligations; care and treatment; informed consent; and resource sharing.ConclusionThe consultation revealed that while there have been few attempts to find convergence on ethical issues between HIV/AIDS, TB and malaria vaccine trial fields to date, there is much common ground and scope for convergence work between stakeholders in the three fields. (shrink)

BackgroundStudies have shown that research participants fail to appreciate the difference between research and medical care, labeling such phenomenon as a "therapeutic misconception" (TM). Since research activity involving human participants is increasing in the Middle East, qualitative research investigating aspects of TM is warranted. Our objective was to assess for the existence of therapeutic misconception amongst Egyptians.MethodsStudy Tool: We developed a semi-structured interview guide to elicit the knowledge, attitudes, and perspectives of Egyptians regarding medical research.Setting: We recruited individuals from the (...) outpatient settings (public and private) at Ain Shams University in Cairo, Egypt.Analysis: Interviews were taped, transcribed, and translated. We analyzed the content of the transcribed text to identify the presence of a TM, defined in one of two ways: TM1 = inaccurate beliefs about how individualized care can be compromised by the procedures in the research and TM2 = inaccurate appraisal of benefit obtained from the research study.ResultsOur findings showed that a majority of participants (11/15) expressed inaccurate beliefs regarding the degree with which individualized care will be maintained in the research setting (TM1) and a smaller number of participants (5/15) manifested an unreasonable belief in the likelihood of benefits to be obtained from a research study (TM2). A total of 12 of the 15 participants were judged to have expressed a TM on either one of these bases.ConclusionThe presence of TM is not uncommon amongst Egyptian individuals. We recommend further qualitative studies investigating aspects of TM involving a larger sample size distinguished by different types of illnesses and socio-economic variables, as well as those who have and have not participated in clinical research. (shrink)

Next SectionThe current focus on early intervention trials in Alzheimer's disease research raises particular ethical issues. These arise out of problems of validating study results and translating them into general practice for one thing and out of unwanted effects of an uncertain diagnosis for diagnosed people for another. The first addresses the demands of scientific research compared to those of medical practice, questioning how the medical value of clinical trials is evaluated. The second relates the scientific and medical value of (...) early intervention trials to the normative value of an uncertain diagnosis. Are people who are diagnosed with a potential early form of AD in clinical studies patients proper—although they would not have been diagnosed with the given “disease” in non-research-oriented medical settings? The very problem of framing this question in terms of diagnostic misconceptions connects conceptual with ethical issues of research into preclinical stages of neurodegenerative diseases. (shrink)

The high price of drugs is receiving due consideration from ethicists, policymakers, and legislators. However, much of this attention has focused on the difference between the cost of drug development and company profits and the possible laws and regulations that could limit a drug’s price once it reaches market. By contrast, little attention has been paid to the ethical implications of high drug prices for the research subjects whose bodies were essential to the drug’s development. Indeed, the future price of (...) a drug is routinely ignored and treated as unknowable during the ethical evaluation of the clinical trials that support its development. In this paper, I will argue that ignoring the future price of a drug during the research process is in tension with all three of the major principles of research ethics: it fails to show respect for the research participants, undermines the quality of risk/benefit judgements made by ethical review committees, and makes it impossible to judge future patient access and assess justice. (shrink)

All major research ethics policies assert that the ethical review of clinical trial protocols should include a systematic assessment of risks and benefits. But despite this policy, protocols do not typically contain explicit probability statements about the likely risks or benefits involved in the proposed research. In this essay, I articulate a range of ethical and epistemic advantages that explicit forecasting would offer to the health research enterprise. I then consider how some particular confidence levels may come into conflict with (...) the principles of ethical research. (shrink)

To date, ethics discussions about stem cell research overwhelmingly have centered on the morality and acceptability of using human embryonic stem cells. Governments in many jurisdictions have now answered these “first-level questions” and many have now begun to address ethical issues related to the donation of cells, gametes, or embryos for research. In this commentary, we move beyond these ethical concerns to discuss new themes that scientists on the forefront of NRM development anticipate, providing a preliminary framework for further discussion (...) between scientists and ethicists. Fostering strong partnerships between neuroscientists and ethicists that operate and collaborate within this evolving framework will maximize the translation of NRM discoveries on the brain into cures that are safe and address the needs of science and society. (shrink)

Twenty-five years after the term "therapeutic misconception’ (TM) first entered the literature, most commentators agree that it remains widespread. However, the majority of scholarly attention has focused on the reasons why a patient cum human subject might confuse the goals of research with the goals of therapy. Although this paper addresses the social and cultural factors that seem to animate the TM among subjects, it also fills a niche in the literature by examining why investigators too might operate under a (...) similar confusion. In framing these issues, the paper expressly adopts a Wittgensteinian approach to evaluating the TM, suggesting that interlocutors do not need any analytic definition of the TM to use the term meaningfully in thinking about the moral implications of the TM in practice. (shrink)

Clinical cases of frontal lobe lesions have been significantly associated with acquired aggressive behaviour. Restoring neuronal and cognitive faculties of aggressive individuals through invasive brain intervention raises ethical questions in general. However, more questions have to be addressed in cases where individuals refuse surgical treatment. The ethical desirability and permissibility of using intrusive surgical brain interventions for involuntary or voluntary treatment of acquired aggressiveness is highly questionable. This article engages with the description of acquired aggressiveness in general, and presents a (...) rare clinical case to illustrate the difficulties of treating this population. To expand the debate further, this article explores the ethics related to invasive brain surgery in three parts: a) it examines coercive involuntary invasive brain surgery for the benefit of protecting others on individuals suffering from acquired aggressiveness who lack decision-making capacities to consent; b) it addresses voluntary psychosurgery on individuals suffering from acquired aggressiveness who are competent to consent; and, c) it questions whether acquired aggressive individuals, who are legally competent, have a duty to consent to invasive brain surgery, in order to maintain their autonomy by reducing or even eliminate their aggressive drives. Ensuring the safety and efficacy of surgical brain interventions could increase the ethical permissibility of voluntary treatment, but it would not necessarily entail ethical justification for proceeding with invasive brain surgery for treatment of intractable acquired aggressive behaviour. (shrink)

Seven specific challenges in patient vulnerability related to neurosurgical advancement highlight needed augmentations for standards in innovation and research that do not unduly inhibit access to potential therapies while assuring just treatment of patients.

The vulnerability of patients receiving significantly innovative neurosurgical procedures, either as research or as non-standard therapy, presents particularly potent challenges for those attempting to substantially advance clinical Neurosurgical practice in the most ethically and efficacious manner. This beginning formulation has built into it several important notions about research participation, balancing values, and clinical advancement in the context of neurological illness. For the time being, allow vulnerability to act as a placeholder for circumstances or states of being wherein the established checks (...) and balances of power and interest are no longer sufficient in promoting the just treatment of persons. Further, the phrase to substantially advance Neurosurgical practice encompasses radical innovation as well as significant research into new procedures. Finally, few of these explorations involve true randomized placebo controlled trials, but rather they enroll patients rightfully hoping for some benefit by means of undergoing the procedure.When a neurosurgeon asks me, as an ethicist, to meet with a patient who has medically refractory disease and no good standard therapy options remaining, he is asking for help concerning whether to offer, as a last chance, an unproven therapy as either innovation or research. (shrink)

Most regulations and guidelines require that potential research participants be told a great deal of information during the consent process. Many of these documents, and most of the scholars who consider the consent process, assume that all this information must be disclosed because it must all be understood. However, a wide range of studies surveying apparently competent participants in clinical trials around the world show that many do not understand key aspects of what they have been told. The standard view (...) of the conditions for valid consent therefore implies that these people have failed to give valid consent to research participation. In this paper we argue that the standard view is false. The primary function of the requirement that researchers disclose information about a study is the avoidance of illegitimate control over someone’s consent decision, which is a form of fraud.We derive the content and manner of appropriate disclosure by analysing the ways in which the manipulation of information can invalidate consent. Our analysis shows that the informational requirements for valid consent are conceptually distinct and thus unlikely to have identical contents. This implies that consent can be valid when not everything that ought to be disclosed by the person asking for consent is understood by the person who proffers it. (shrink)

Most regulations and guidelines require that potential research participants be told a great deal of information during the consent process. Many of these documents, and most of the scholars who consider the consent process, assume that all this information must be disclosed because it must all be understood. However, a wide range of studies surveying apparently competent participants in clinical trials around the world show that many do not understand key aspects of what they have been told. The standard view (...) of the conditions for valid consent therefore implies that these people have failed to give valid consent to research participation. In this paper we argue that the standard view is false. The primary function of the requirement that researchers disclose information about a study is the avoidance of illegitimate control over someone’s consent decision, which is a form of fraud.We derive the content and manner of appropriate disclosure by analysing the ways in which the manipulation of information can invalidate consent. Our analysis shows that the informational requirements for valid consent are conceptually distinct and thus unlikely to have identical contents. This implies that consent can be valid when not everything that ought to be disclosed by the person asking for consent is understood by the person who proffers it. (shrink)

At least since the seminal work of the (US) National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research in the 1970s, a fundamental distinction between research and practice has underwritten both conceptual work in research ethics and regulations governing research involving human subjects. Notwithstanding its undoubted historical importance, I believe the distinction is problematic because it misrepresents clinical inquiry. In this essay, I aim to clarify the character of clinical inquiry by identifying crucial contextual constraints on (...) justification constitutive of clinical science. This analysis shows that, from an epistemological point of view, clinical research and clinical practice are not sharply distinct but intimately intertwined. This result is important in its own right—an enriched understanding of the epistemology of clinical research is valuable in and of itself. But this result is also important because it has profound implications for the ethics of human subjects research. (shrink)