Authorising euthanasia and assisted suicide with advance euthanasia directives is permitted, yet debated, in the Netherlands. We focus on a recent controversial case in which a Dutch woman with Alzheimer’s disease was euthanised based on her AED. A Dutch euthanasia review committee found that the physician performing the euthanasia failed to follow due care requirements for euthanasia and assisted suicide. This case is notable because it is the first case to trigger a criminal investigation since the 2002 Dutch euthanasia law (...) was enacted. Thus far, only brief descriptions of the case have been reported in English language journals and media. We provide a detailed description of the case, review the main challenges of preparing and applying AEDs for persons with dementia and briefly assess the adequacy of the current oversight system governing AEDs. (shrink)

The revised Common Rule adopts the reasonable person standard to guide research disclosure. Some members of the research community contend that the standard is confusing and ill-suited to the research oversight system. Yet the revised rule is not as radical as it might seem. During the 1970s, judges started using the standard to evaluate negligence claims brought by injured patients who said doctors had failed to obtain informed consent to the harmful procedures. In its influential Belmont Report, the National Commission (...) recommended application of a “reasonable volunteer standard” to guide IRBs evaluating research disclosures. Evidence also suggests that IRBs often invoke the reasonable person standard in deliberations about consent forms. But past application of the standard has been informal and uneven. Robust application of the reasonable person standard will require researchers and IRBs to learn more about what ordinary people want and need to know about the studies they are invited to join. Input from people with personal experience as study participants could be particularly useful to this effort. (shrink)

Nanomedicine is yielding new and improved treatments and diagnostics for a range of diseases and disorders. Nanomedicine applications incorporate materials and components with nanoscale dimensions where novel physiochemical properties emerge as a result of size-dependent phenomena and high surface-to-mass ratio. Nanotherapeutics and in vivo nanodiagnostics are a subset of nanomedicine products that enter the human body. These include drugs, biological products, implantable medical devices, and combination products that are designed to function in the body in ways unachievable at larger scales. (...) Nanotherapeutics and in vivo nanodiagnostics incorporate materials that are engineered at the nanoscale to express novel properties that are medicinally useful. These nanomedicine applications can also contain nanomaterials that are biologically active, producing interactions that depend on biological triggers. Examples include nanoscale formulations of insoluble drugs to improve bioavailability and pharmacokinetics, drugs encapsulated in hollow nanoparticles with the ability to target and cross cellular and tissue membranes and to release their payload at a specific time or location, imaging agents that demonstrate novel optical properties to aid in locating micrometastases, and antimicrobial and drug-eluting components or coatings of implantable medical devices such as stents. (shrink)

Translational science is a 21st century mission. Government officials and industry leaders are making huge investments in an attempt to transform more basic science discoveries into therapeutic applications. Scientists and policymakers express great excitement about the medical advances that could come with the current bench-to-bedside campaign.A key step in translational science is the move from animal and other preclinical studies to initial human testing. Researchers ability to predict human effects is limited, and first-in-human tests present significant uncertainty. Participants in this (...) form of research face risks and can experience serious, even lethal, harm. Well-known incidents involving Jolee Mohr and Jesse Gelsinger, as well as subjects in the 2006 study of the investigational agent TGN1412, show the dangers that can arise in early human research.The bench-to-bedside campaign will need many volunteers to participate in early human testing. Investigators and regulators must not allow the policy enthusiasm for translational science to overshadow the commitment to protect human subjects. Participants in exploratory research are diverse and as a group lack characteristics usually associated with vulnerable populations, such as impaired decisional ability or economic or educational disadvantage. (shrink)

The 21st-century translational science campaign could lead to an increase in first-in-human trials. As tests of investigational interventions move from the laboratory to human research, scientists, officials, and review committees should address ongoing concerns about the ethics of FIH trials. In this article, I describe three ethical considerations relevant to all FIH trials: the requirement for adequate preclinical research; study design safeguards; and choice of subject population. I also examine specific ethical considerations relevant to the three subject populations involved in (...) FIH research. I recommend a variety of actions that could increase subject protection and the value of the information generated in FIH trials. (shrink)

Volume 20, Issue 5, June 2020, Page 20-22.

The term “therapeutic misconception” was coined in 1982 by Paul Appelbaum, Loren Roth, and Charles Lidz. Appelbaum and his colleagues interviewed participants in several psychiatric studies, including a drug trial with a placebo control arm. Appelbaum's group found that many people were unaware of the differences between participating in a study and receiving treatment in the clinical setting. Rather than understanding these differences, study participants tended to believe that therapy and research were governed by the same primary goal: to advance (...) the individual patient's best interests. Appelbaum's group labeled this mistaken belief the therapeutic misconception. (shrink)

Research subjects do not always conform to research requirements. When their personal interests conflict with the demands of participation, some subjects surreptitiously break the rules. These subjects are subversive — they undermine the research endeavor. In rejecting the restrictions research imposes, subversive subjects diminish the value of research results. From one vantage point, subversive subjects engage in unethical behavior. They create risks to themselves and others; they also disregard ethical responsibilities to adhere to research agreements and tell the truth. At (...) the same time, subversive subjects expose ethical problems in the design and conduct of clinical trials. Features of the research environment create fertile ground for subject subversion. Intensified policing and guidance are two common strategies for reducing subject subversion, but collaborative reforms are more consistent with the partnership model of clinical research. (shrink)

Research using human embryonic stem cells raises an array of complex ethical issues, including, but by no means limited to, the moral status of developing human life. Unfortunately much of the public discussion fails to take into account this complexity. Advocacy for liberal and conservative positions on human embryonic stem cell research can be simplistic and misleading. Ethical concepts such as truth-telling, scientific integrity, and social justice should be part of the debate over federal support for human embryonic stem cell (...) research. Moreover, the debate should be conducted in accord with principles of deliberative democracy, including respect for people holding competing views. (shrink)

We are grateful to Jongsma et al 1 for their interest in our article analysing the case of ‘Mrs A’, a Dutch woman with Alzheimer’s disease who received euthanasia based on her advance euthanasia directive.2 Their commentary criticises two elements of our analysis. First, the authors believe our reasons for doubting that Mrs A had the capacity to write and revise an AED rely on ‘partial’ empirical data and rest on normative errors. Second, they use two of our statements to (...) suggest we must endorse some implausible claims, for example, that ‘… in all situations and for all people, current well-being should always take precedence over all other values’. Jongsma et al assert: ‘Miller et al argue that people with dementia are impaired to make decisions.’ This casts our probabilistic claim about Mrs A’s capacity as an absolute claim about persons with dementia in general. It also implies we are using an outdated diagnosis-based view of capacity. The accusation then becomes explicit : > … several empirical studies have shown that patients with dementia are able to actively participate in qualitative studies and can respond to open questions in a meaningful way,[2-8] as well that they are able to complete an advance directive in the early phases of dementia.[9, 10] One can therefore not simply conclude on the basis of the diagnosis of dementia …. (shrink)

Novel nanomedical interventions require human testing to evaluate their safety and effectiveness. To establish a proper evidentiary basis for human trials, nanomedical innovations must first be subjected to animal and other laboratory testing. But it is uncertain whether the traditional laboratory approaches to safety evaluation will supply adequate information on nanotechnology risks to humans. This uncertainty, together with other features of nanomedical innovation, heightens the ethical challenges in conducting FIH nanotrials.

Lynne Rudder Baker, Saving Belief: A Critique of Physicalism Princeton: Princeton University Press, 1987, xii + 177 pp. Daniel C. Dennett, The Intentional Stance Cambridge: MIT Press, 1987, xi + 388 pp. Paul M. Churchland, Matter and Consciousness Cambridge: MIT Press, revised edition, 1988, xii + 184 pp.

In 1998, researchers established the first human embryonic stem cell line. Their scientific triumph triggered an ethics and policy argument that persists today. Bioethicists, religious leaders, government officials, patient advocates, and scientists continue to debate whether this research poses a promise, a threat, or a mixed ethical picture for society.Scientists are understandably excited about the knowledge that could come from studying human embryonic stem cells. Most of them believe these cells offer a precious opportunity to learn more about why diseases (...) develop and how they might be prevented or attacked. In their quest to gain support for stem cell research, scientists and others have claimed that the research could generate cures and treatment for everything from heart disease to cancer. (shrink)

Under current U.S. law, physicians may prescribe drugs and devices in situations not covered on the label approved by the Food and Drug Administration. Those supporting this system say that requiring FDA approval for off-label uses would unnecessarily impede the delivery of benefits to patients. Patients do benefit from off-label prescribing that is supported by sound scientific and medical evidence. In the absence of such evidence, however, off-label prescribing can expose patients to risky and ineffective treatments. The medical community and (...) federal authorities should more actively promote patients' interests in receiving beneficial off-label treatments. To exercise responsible self-regulation, members of the medical community must determine whether available evidence justifies specific off-label uses and must promote information-gathering when the evidence is inadequate. Physicians should also discuss with patients the uncertainties accompanying off-label uses. Federal authorities should more closely monitor the effects of off-label prescribing and adopt other measures to reduce harm and enhance benefits produced by off-label prescribing. (shrink)

Care workers and families often engage in deception in everyday interactions with people affected by dementia. While benevolent deception can be justified, there are often more respectful and less risky ways to help people with dementia seeking to make sense of their lives.

The biomedical literature and popular media are full of upbeat reports about the health benefits we can expect from medical innovations using nanotechnology. Some particularly enthusiastic reports portray nanotechnology as one of the innovations that will lead to a significantly extended human life span. Extreme enthusiasts predict that nanotechnology “will ultimately enable us to redesign and rebuild, molecule by molecule, our bodies and brains….”Nanomaterials have special characteristics that could contribute to improved patient care. But the same characteristics that make nanotechnology (...) promising also present risks to humans exposed to nanomaterials. A failure to appreciate these risks could jeopardize the research effort. As others have pointed out, if nanomedical interventions produce unexpected human harm, a loss of public and government support for nanomedicine is likely to follow.Like other forms of medical innovation, novel nanomedical interventions require human testing to evaluate their safety and effectiveness. (shrink)

Scientific reports about clinical research appear objective and straightforward. They describe a study's findings, methods, subject population, number of subjects, and contribution to existing knowledge. The overall picture is pristine: the research team establishes the requirements of study participation and subjects conform to these requirements. Readers are left with the impression that everything was done correctly, by the book.In other places, however, one finds a different and messier picture of clinical research. In this picture, research subjects deviate from the prescribed (...) plan. One author contrasted the “tidy graphics” and “crisp prose” of the New England Journal of Medicine's HIV/AIDS trial publications with reports that subjects shared medications and broke other trial rules. Awareness of this behavior, he wrote, could lead insiders to “conclude that knowledge was resting on something rather less solid than bedrock.”. (shrink)

In 2006, I was diagnosed with cancer. This began a crash course in real-world medical ethics. Having cancer was awful, but it was instructive, too. The experience gave me a new understanding of what my profession is about. Individuals in the bioethics field often address topics related to cancer, such as medical decision-making, the patient-physician relationship, clinical trials, and access to health care. Yet few engaged in this work have lived with cancer themselves. Experience as a cancer patient or family (...) caregiver extends and deepens one’s thinking about serious illness and bioethics. During my time as a cancer patient, I kept in touch with several colleagues immersed in their own cancer .. (shrink)

Off-label prescribing is an integral part of contemporary medicine. Many patients benefit when they receive drugs or devices under circumstances not specified on the label approved by the Food and Drug Administration. An off-label use may provide the best available intervention for a patient, as well as the standard of care for a particular health problem. In oncology, pediatrics, geriatrics, obstetrics, and other practice areas, patient care could not proceed without off-label prescribing. When scientific and medical evidence justify off-label uses, (...) physicians promote patients’ interests by prescribing products off label.Off-label prescribing can also harm patients, however. The potential for harm is greatest when an offlabel use lacks a solid evidentiary basis. A 2006 study examining prescribing practices for 169 commonly prescribed drugs found high rates of off-label use with little or no scientific support. Researchers examining off-label use in U.S. children’s hospitals concluded, “[W]e still have incomplete knowledge about the safety and efficacy of many medications commonly used to treat children across a range of drug classes and clinical diagnoses.”. (shrink)

The first set of case studies on animal use, this volume offers a thorough, up-to-date exploration of the moral issues related to animal welfare. Its main purpose is to examine how far it is ethically justifiable to harm animals in order to benefit mankind. An excellent introduction provides a framework for the cases and sets the background of philosophical and moral concepts underlying the subject. Sixteen original, previously unpublished essays cover controversies associated with the human use of animals in a (...) broad range of contexts, including biomedical, behavioral, and wildlife research, cosmetic safety testing, education, the food industry, commerce, and animal use as pets and in religious practices. Scientific research is accorded the closest scrutiny. The authors represent a wide range of expertise within their specialized areas of research--physiology, public policy, ethics, philosophy, law, veterinary science, and psychology. The careful analysis of each case makes it possible to elevate the discourse beyond over-simplified positions, and to demonstrate the complexity of the issues. The Human Use of Animals will be welcomed by students and faculty in law, philosophy, ethics, public policy, religion, medicine, and veterinary medicine. It will also interest activists in the animal protection movement, and members of animal protection organizations and Institutional Animal Care and Use Committees. (shrink)

It's not unusual to hear someone say, ‘I'd rather be dead than have Alzheimer's’. In ‘Alzheimer Disease and Preemptive Suicide’,1 Dena Davis explains why this is a reasonable position. People taking this position will welcome the discovery of biomarkers permitting very early AD diagnosis, Davis suggests, for this will enable more of them to end their lives while they remain motivated and able to do so. At the same time, Davis observes, people would have less reason to resort to the (...) drastic remedy of pre-emptive suicide if they had absolute authority over the medical treatment they received as patients with dementia; but the threat of pre-emptive suicide is not, in my view, a sufficient reason to grant competent individuals that authority.If preclinical diagnosis of AD becomes possible, some pre-emptive suicides will probably occur. There would be no ethical or practical way to ban such suicides, and it would be silly to try. Clinicians will undoubtedly try to discourage people seeking biomarker information in furtherance of a suicide plan, but savvy individuals will simply conceal their true motivation for having the tests. The real problem for people intent on self-destruction is that biomarkers are unlikely to deliver a clear suicide signal.First, as Davis notes, work on biomarkers remains in the research stage. No one yet knows whether biomarker tests will prove accurate enough to warrant clinical use. Second, even clinically accepted biomarker tests will generate imperfect information about future disease. Biomarkers may produce more accurate estimates of a person's risk of developing AD, but like all predictive tests, they will also yield false positive and negative results. The …. (shrink)

Much of the public debate over laboratory animal use has focused on either the scientist's demand for absolute freedom of inquiry, or the abolitionist's demand for an end to animal use in science. Yet many recent proposals for reform seek instead to balance the interests of laboratory animals in avoiding harm against the interests of research beneficiaries in continued animal use. This essay is an analysis of the intermediate reform positions and their underlying ethical principles. Keywords: animal research, animal experimentation, (...) ethics CiteULike Connotea Del.icio.us What's this? (shrink)

Last November, soon after Colorado became the latest state to authorize physician-assisted suicide, National Public Radio's The Diane Rehm Show devoted a segment to legalization of “physician assistance in dying,” a label that refers to both physician-assisted suicide and voluntary active euthanasia. Although the segment initially focused on PAD in the context of terminal illness in general, it wasn't long before PAD's potential application to dementia patients came up. A caller said that her mother had Alzheimer's disease and was being (...) cared for at great expense. Suspecting that she will suffer the same fate, the caller reported that she had included in her will “my specific request that if I should be diagnosed, and it is legal to do so, I would like to opt out of a life and many years of suffering.” A few countries, such as the Netherlands and Belgium, already allow PAD for dementia in certain circumstances. It wouldn't be surprising to see a U.S. legalization effort in the coming years. (shrink)

Pharmaceutical companies are major sponsors of biomedical research. Most scholars and policymakers focus their attention on government and academic oversight activities, however. In this article, I consider the role of pharmaceutical companies’ internal ethics statements in guiding decisions about corporate research and development (R&D). I review materials from drug company websites and contributions from the business and medical ethics literature that address ethical responsibilities of businesses in general and pharmaceutical companies in particular. I discuss positive and negative uses of pharmaceutical (...) companies’ ethics materials and describe shortcomings in the companies’ existing ethics programs. To guide employees and reassure outsiders, companies must add rigor, independence, and transparency to their R&D ethics programs. (shrink)