Tag: clinical ethics

Bioethics for Breakfast: Aducanumab, Alzheimer’s: Having That Conversation

Bioethics for Breakfast Seminars in Medicine, Law and Society

Leonard M. Fleck, PhD, and Irving E. Vega, PhD, presented at the March 24 Bioethics for Breakfast session, offering perspectives and insight on the topic “Aducanumab, Alzheimer’s: Having That Conversation.” Bioethics for Breakfast is generously sponsored by Hall, Render, Killian, Heath & Lyman. This session was the second of a two-part series on the theme “Paradoxes of Aging: Living Longer and Feeling Worse.” The presentation portion of the session was recorded and is available to watch on our website.

Aducanumab, a drug designed to treat Alzheimer’s disease, has been the focus of intense medical, scientific, social, and ethical controversy. The FDA Advisory Commission voted almost unanimously not to approve the drug. The research trials failed to show that aducanumab offered significant clinical benefit to patients in the early stages of Alzheimer’s, and notably the enrollment of Black and Latino patients was disproportionately low. It came as a surprise that the FDA itself ultimately gave its approval to the drug, which costs $28,000 per year and is administered monthly through infusion in a hospital setting.

Fleck provided background on Aducanumab and the clinical trials carried out by the developer, Biogen, that led them to seek FDA approval. He defined the different stages of Alzheimer’s disease, noting that over six million Americans currently have been diagnosed with some degree of Alzheimer’s. Fleck also outlined the FDA’s approval process, including their vote to grant emergency use authorization with the expectation of phase four clinical trials completed within nine years. He also pointed out that Aducanumab’s effects are limited to mild cognitive impairment and mild Alzheimer’s, with no benefit in more advanced stages. However, there have been no other Alzheimer’s disease drugs in the past twenty years with promise of significant benefit.

Bringing up concerns of social justice, Fleck discussed the cost Aducanumab within U.S. health spending, particularly within the Medicare program. It is estimated that 85% of the estimated 3.1 million Americans with a mild Alzheimer’s diagnosis are Medicare eligible, meaning the annual cost to Medicare would be in the hundreds of billions of dollars for the drug and its associated costs. Fleck asked attendees to consider whether this spending would be a just use of limited health care resources.

Vega offered attendees questions to consider: is there sufficient evidence about the safety of the drug? Is there sufficient evidence about the effectiveness of the drug? Does the treatment address health disparities in Alzheimer’s disease? He discussed the biology of Alzheimer’s disease, outlining its effect on the brain, and pointing out what is still unknown about the disease. After defining scientific rigor, Vega walked attendees through concerns about the Aducanumab clinical trials, such as participant age and the inadequate representation of Black, Hispanic, American Indian or Alaska Native, and Native Hawaiian or Pacific Islander populations.

Focusing on these disparities, Vega shared facts pertaining to Black Americans being twice as likely to have Alzheimer’s compared to non-Latino white Americans, and Latino Americans being 1.5 times as likely, compared to non-Latino white Americans. Disparities exist with increased likelihood of comorbidities like stroke, heart disease, obesity, and diabetes. Given these facts, Vega shared concern for observed adverse side effects of Aducanumab, particularly brain swelling, microbleeds, and slow brain bleeding.

Questions from attendees generation discussion about advocacy work, insurance companies, and direct and indirect costs of Alzheimer’s disease. Fleck and Vega noted the cost of care for an individual with Alzheimer’s, in a long term care facility, is typically in the $80,000-$100,000 range per year. Indirect costs include the lost wages of caregivers, and stress experienced by loved ones. Vega also importantly pointed out the context of the approval of Aducanumab: a global pandemic, COVID-19 vaccine development, and the subsequent spread of misinformation. Attendees also participated in polling questions with hypothetical situations, asking whether they agreed or disagreed with the scenarios. Responses were varied, highlighting the complexities of the topic.

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About the speakers

Leonard M. Fleck, PhD, is a professor in the Center for Bioethics and Social Justice and the Department of Philosophy at Michigan State University. Fleck’s interests focus on medical ethics, health care policy, priority-setting and rationing, and reproductive decision-making. He explores the role of community dialogue (rational democratic deliberation) in addressing controversial issues of ethics and public policy related to emerging genetic technologies. More recently, he has been working on a book-length manuscript that addresses a number of ethical and policy issues related to precision medicine, primarily in a cancer treatment context.

Irving E. Vega, PhD, obtained his undergraduate degree in Biology from the University of Puerto Rico-Mayaguez Campus. He continued his research training in the Department of Cell Biology and Neuroscience at the Graduate School of New Brunswick, Rutgers University, earning his PhD. Vega completed a postdoctoral fellowship in the Neuroscience Department at Mayo Clinic Jacksonville, where he developed his research career focusing on the pathobiology of Alzheimer’s disease. Vega joined the faculty as an associate professor in the Department of Translational Neuroscience at the Michigan State University College of Human Medicine campus in Grand Rapids, MI in 2014. His research focuses on molecular and biochemical mechanisms that modulate the accumulation of pathological tau proteins in Alzheimer’s disease and related dementias. Vega is also working on ethnic disparities and the influence of ethnoracial factors on blood biomarkers in Alzheimer’s disease.

“There’s no proof that anything works!” The ethics of COVID-19 research

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This post is a part of our Bioethics in the News seriesBioethics in the News purple and teal icon

By Robyn Bluhm, PhD

The New York Times Magazine recently published a long-form story about the tension between treating patients with COVID-19 by any means that might improve their chances of survival and recovery, and enrolling them in clinical trials to establish the safety and efficacy of these treatments, thus improving care both for future patients and for those who survived the trial. As with many stories about health care in the current pandemic, this article both raises perennial issues in bioethics and shows them in their starkest form: the seriousness of the condition of these patients and the lack of knowledge about how best to help them mean that the ethical dilemma described in the story is particularly clear. But a closer look at work in bioethics and the epistemology of clinical research suggests that, while the dilemma is clear, there are more ways forward than the two incompatible ways portrayed in the story.

The story begins by describing the clash between a critical-care physician faced with a COVID-19 patient whose condition was worsening, and a researcher who had enrolled that patient in a clinical trial. The former wanted to give the patient a higher-than-standard dose of the anticoagulant she was being treated with, even though this might mean that she would need to be withdrawn from the trial. The latter advocated for the importance of maintaining the integrity of the study, saying that acting on instinct instead of on evidence “was essentially ‘witchcraft’.”

Unsurprisingly, this characterization did not go over well with the other doctors in the meeting. A less contentious way of describing the situation might have been to say that, while doctors use their clinical judgment to make decisions about how best to use available evidence in caring for a particular patient, this only works when there is evidence available. And everyone agrees that, in the case of COVID-19, there is horrifyingly little evidence. This means that enrolling COVID-19 patients in clinical trials is not depriving them of standard care (care that such patients would ordinarily receive if not in the trial)–standard care for this condition does not yet exist.

Nurse with medical equipment illustrated image
Image description: An illustration of a health care worker wearing blue scrubs, head covering, and face covering. Surrounding them are a stethoscope, face mask, syringe and surgical tools, thermometer, and microscope. The background is light pink. Image source: sunshine-91/Vecteezy.

There is a lot to think about here. Importantly, it’s not the case that the doctors treating seriously ill patients had no idea what to do. They had a wealth of experience treating patients with severe viral infections, with acute respiratory distress syndrome, with cardiac arrest, or with pathological immune reactions (the “cytokine storm” sometimes seen in chemotherapy patients). Some of this knowledge informed the care of early COVID-19 patients, raising the question of which treatments could be successfully generalized to this new patient group.

The notion of generalizable knowledge is in fact central to research ethics. The Belmont Report, which guides research ethics oversight in the United States, draws a bright line between research and clinical practice on the basis of their ostensibly distinct goals. Research aims to provide generalizable knowledge, while clinical practice aims to benefit an individual patient. This way of drawing the distinction meant that when physicians depart from standardly-accepted care in the treatment of an individual patient, it does not count as research (and therefore does not require ethics review). It also leads to the problem described above: enrolling a patient in a research study requires that they forgo their right to individualized care and are treated according to study protocol. Deviations from the protocol, such as the one described in the opening of the New York Times story, are prohibited. Patients whose care does not follow the protocol will usually be withdrawn from the study.

But this sharp distinction between research and practice also makes assumptions about the kind of clinical research being conducted. Schwartz and Lellouch (1967) distinguish between “explanatory” and “pragmatic” approaches to clinical trials. Explanatory trials are designed to minimize the influence of any factors, other than the experimental therapy, that could affect the outcome being measured. These other factors include additional medications and the presence of comorbid disease. Pragmatic trials, by context, are designed to resemble actual clinical practice, where patients often take more than one medication and often have more than one health problem. Pragmatic trials may also enroll a wider variety of participants (especially older participants), permit alterations in the study protocol, be more flexible in the timing of outcome measurement; in general, they are more flexible in their design and analysis. A given trial will fall somewhere on the spectrum between “highly explanatory” and “highly pragmatic” in its design.

In the case of COVID-19, there are good reasons to favor trials that are more pragmatic. First, there are so many factors that might affect prognosis (or were previously thought to do so) – age, gender, weight, blood type, various pre-existing conditions – that the study population cannot be narrowly defined. If it is, then the results of the study will apply only to people in that narrow population. Second, care for critically ill patients is rapidly developing. Even in the absence of an established drug regimen, survival rates have been improving. This means that by the time a trial is completed, the experimental therapy will be implemented in a very different context of care. Perhaps more importantly, because of these first two reasons, a strict, explanatory trial is less likely to give generalizable knowledge than a more pragmatic one (Bluhm and Borgerson, 2018). Research that reflects clinical practice is more likely to be useful in improving clinical practice.

Robyn Bluhm photoRobyn Bluhm, PhD, is an Associate Professor with a joint appointment in the Department of Philosophy and Lyman Briggs College at Michigan State University. She is a co-editor of The Bloomsbury Companion to Philosophy of Psychiatry.

Join the discussion! Your comments and responses to this commentary are welcomed. The author will respond to all comments made by Thursday, September 3, 2020. With your participation, we hope to create discussions rich with insights from diverse perspectives.

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More Bioethics in the News from Dr. Bluhm: Philosophy, Mental Illness, and Mass Shootings; “Ask your doctor” – or just check Instagram?; Antibiotics: No Clear Course; To Floss or Not to Floss? That’s not the question

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Announcing the Fall 2019 Bioethics Brownbag & Webinar Series

Green brownbag/webinar iconThe Center for Ethics and Humanities in the Life Sciences at Michigan State University is proud to announce the 2019-2020 Bioethics Brownbag & Webinar Series. The series will begin on October 16, 2019. You are invited to join us in person or watch live online from anywhere in the world! Information about the fall series is listed below. Please visit our website for more details, including the full description and speaker bio for each event.

Fall 2019 Series Flyer

Oct 16 calendar iconSpinal Cord Injury: Everything You Wanted to Know But Were Afraid to Ask
Wednesday, October 16, 2019

There are many dimensions to a happy and healthy life, and everyone would agree that life is complicated. But when multiplied by a spinal cord injury (SCI), the complexity of life can be off the charts—what we used to take for granted becomes a monumental challenge. This talk with explore life with SCI from a first-person perspective.

Mark Van Linden, MSA, is President of Adversity Solutions LLC and a spinal cord injury patient since 2009.

Nov 13 calendar iconSpeaking for the Dying: Life-and-Death Decisions in Intensive Care
Wednesday, November 13, 2019

Seven in ten older Americans who require medical decisions in the final days of life lack capacity to make them. For many of us, our biggest life-and-death decisions—literally—will therefore be made by someone else. But how will they decide for us?

Susan P. Shapiro, PhD, is a Research Professor at the American Bar Foundation.

In person: These lectures will take place from 12:00-1:00 PM in C102 (Patenge Room) East Fee Hall on MSU’s East Lansing campus. Feel free to bring your lunch! Beverages and light snacks will be provided.

Online: Here are some instructions for your first time joining the webinar, or if you have attended or viewed them before, go to the meeting!

Can’t make it? Every lecture is recorded and posted for viewing in our archive. If you’d like to receive a reminder before each lecture, please subscribe to our mailing list.

Dr. Fleck presents on elder ethics at International Bioethics Retreat in Paris

Leonard Fleck photoCenter Acting Director and Professor Dr. Leonard Fleck recently presented at the 2019 International Bioethics Retreat, held in Paris, France on June 26-28. Dr. Fleck chaired a session titled “In the Clinic” which featured topics on clinical ethics and medical decision-making.

In a session titled “Elder Ethics,” Dr. Fleck presented a talk on “Whither Frailty: Ethical, Economic, Medical and Policy Challenges.” Dr. Fleck addressed four key questions: (1) How should frailty be defined as a medical phenomenon? (2) What should be the scope and limits of respect for autonomy in the case of the frail elderly? (3) What should be the scope and limits of acceptable risk of harm to the frail elderly in the case of aggressive medical or surgical interventions? This question pertains to the responsibilities of physicians and surgeons in proposing such interventions. (4) What issues of health care justice deserve the attention of policymakers when it comes to meeting the health care needs of the frail elderly?

The first problem refers to the complexity of frailty as a medical phenomenon. Frailty is not disability; frailty is primarily associated with the elderly. Some researchers describe frailty as “accelerated aging.” Roughly 38% of individuals over age 90 would be described as being frail. Individuals may be frail and not have any life-threatening medical problems. Most of the frail elderly are able to make medical decisions for themselves, which is why there is the ethical issue of respect for patient autonomy versus justified medical paternalism. Among the behavioral traits of the frail elderly would be reduced activity (prolonged bed rest), very slow mobility, weight loss, extreme old age, diminished handgrip strength, polypharmacy, and social isolation. Clearly, frailty exists along a complex spectrum requiring considerable acuity of judgment to avoid ethical missteps.

To illustrate the potential for ethical missteps, labeling an elderly individual as “frail” can result in inappropriate paternalistic decisions, negative stereotypes, and discrimination. Alternatively, failure to identify an elderly individual as frail can result in overly aggressive medical treatment (and a range of avoidable medical harms) as well as a lack of attention (and resources) that might better address the social needs of the frail elderly that would represent a greater net benefit than aggressive medical treatment.

We might wish to go to the research literature for some guidance. However, there is little actual research regarding the frail elderly and aggressive medical or surgical care. Further, it is difficult to imagine how such research could be accomplished in a way that was not ethically problematic. This makes the responsibilities of physicians in clinical practice who care for the frail elderly all the more challenging.

Dr. Fleck concluded with two points: (1) From the perspective of health care justice, from the perspective of what a just and caring society ought to do, resources should be redirected from aggressive medical care for the frail elderly to their social service needs. However, the fragmented system for financing health care in the U.S. gets in the way of easily making this re-allocation of resources. (2) Soft paternalism will often be ethically justified in caring for the frail elderly considering aggressive medical care. A non-committal stance on the part of physicians in these circumstances, under the ethical guise of respect for patient autonomy, will most often be neither just, nor caring, nor respectful of patient needs and their considered values.

What happens when people express hope for a miracle in the context of medicine?

No Easy Answers in Bioethics logoNo Easy Answers in Bioethics Episode 12

How do patients, their families, or their caregivers express hope for a miracle in the clinical setting? How can medical professionals respond to these desires for a miracle to occur?

Guests Dr. Devan Stahl, Assistant Professor in the Center for Ethics and Humanities in the Life Sciences and Department of Pediatrics and Human Development at Michigan State University, and Dr. Trevor Bibler, Assistant Professor in the Center for Medical Ethics and Health Policy at Baylor College of Medicine, have written on this topic, with articles published in the American Journal of Bioethics and the Journal of Pain and Symptom Management. In this episode they discuss the framework for categorizing the various ways in which people hope for a miracle, while also drawing from experiences they have had as clinical ethicists. They also discuss the importance of not making assumptions when miracle language is used, emphasizing the need for all religious beliefs to be respected by medical professionals.

Ways to Listen

This episode was produced and edited by Liz McDaniel in the Center for Ethics. Music: “While We Walk (2004)” by Antony Raijekov via Free Music Archive, licensed under a Attribution-NonCommercial-ShareAlike License. Full episode transcript available.

About: No Easy Answers in Bioethics is a podcast series from the Center for Ethics and Humanities in the Life Sciences in the Michigan State University College of Human Medicine. Each month Center for Ethics faculty and their collaborators discuss their ongoing work and research across many areas of bioethics—clinical ethics, evidence-based medicine, health policy, medical education, neuroethics, shared decision-making, and more. Episodes are hosted by H-Net: Humanities and Social Sciences Online.

What does it mean to declare brain death in the clinical setting?

No Easy Answers in Bioethics logoWhat does it mean to declare brain death in the clinical setting? How does the language we use surrounding death complicate these situations? What beliefs and philosophies exist regarding what constitutes the death of a person?

Episode 11 of No Easy Answers in Bioethics is now available! This episode features Center for Ethics and Humanities in the Life Sciences faculty members Dr. Devan Stahl and Dr. Tom Tomlinson. They discuss the above questions and more from both clinical ethics and philosophical perspectives. They go over the history of how brain death came to be defined in the United States, and discuss some cases in the news from recent years.

Ways to Listen

This episode was produced and edited by Liz McDaniel in the Center for Ethics. Music: “While We Walk (2004)” by Antony Raijekov via Free Music Archive, licensed under a Attribution-NonCommercial-ShareAlike License. Full episode transcript available.

About: No Easy Answers in Bioethics is a podcast series from the Center for Ethics and Humanities in the Life Sciences in the Michigan State University College of Human Medicine. Each month Center for Ethics faculty and their collaborators discuss their ongoing work and research across many areas of bioethics—clinical ethics, evidence-based medicine, health policy, medical education, neuroethics, shared decision-making, and more. Episodes are hosted by H-Net: Humanities and Social Sciences Online.

Would you ever consent to have your medical procedure broadcast on social media?

No Easy Answers in Bioethics logoEpisode 10 of No Easy Answers in Bioethics is now available! This episode features Dr. Devan Stahl, Assistant Professor in the Center for Ethics and the Department of Pediatrics and Human Development, and Dr. Christian Vercler, Clinical Associate Professor of Plastic Surgery in the Department of Surgery at the University of Michigan and Co-Chief of the Clinical Ethics Service in the Center for Bioethics and Social Sciences in Medicine. Drs. Stahl and Vercler address a trend known as Snapchat surgeons – plastic surgeons who amass sometimes millions of followers on the social media platform Snapchat by posting uncensored videos of operations they are performing. Together they offer their insight and expertise on the issue, and discuss whether these Snapchat performances are ethical. They also delve into the societal norms and power dynamics at play, and address how to move forward within the profession of plastic surgery in a world where social media seems to be here to stay.

Ways to Listen

This episode was produced and edited by Liz McDaniel in the Center for Ethics. Music: “While We Walk (2004)” by Antony Raijekov via Free Music Archive, licensed under a Attribution-NonCommercial-ShareAlike License. Full episode transcript available.

About: No Easy Answers in Bioethics is a podcast series from the Center for Ethics and Humanities in the Life Sciences in the Michigan State University College of Human Medicine. Each month Center for Ethics faculty and their collaborators discuss their ongoing work and research across many areas of bioethics—clinical ethics, evidence-based medicine, health policy, medical education, neuroethics, shared decision-making, and more. Episodes are hosted by H-Net: Humanities and Social Sciences Online.

Dr. Fleck facilitates ethics workshop at Michigan pediatrics conference

Leonard Fleck photoOn September 14, Center Professor and Acting Director Dr. Leonard Fleck and Dr. Kenneth Pituch, MD, ran an ethics workshop at the Michigan Chapter of the American Academy of Pediatrics (MIAAP) 68th Annual Conference. The workshop, “Ethical Challenges in the Care of Seriously Ill Children,” focused on two cases: a growth attenuation case, and a Trisomy-18 newborn case.

The growth attenuation case involved a 7-year-old boy with severe developmental delay related to a CMV infection in utero. Parents are middle-aged and “not in great health.” They requested growth attenuation hormone therapy so that they would be able to manage the care of their child for many more years. No one doubts that they are devoted parents. The relevant ethical considerations concerned the best interests of this child and parental rights to make medical decisions for their children. On the face of it, it looks like the parents are making this decision for their benefit, i.e., easier care management for this child. While this is true, as the discussion brought out, it is also the case that this would be in the best interest of the child as well. More specifically, this child will not be deprived of any life experiences as a result of growth attenuation because of his severe developmental delay. Hence, growth attenuation does not represent a harm to this child.

Dr. Fleck and Dr. Pituch’s other case involved a Trisomy-18 newborn. In the past these children had dismal prospects. Virtually all of them died before age one, most often because of cardiac anomalies. Today, complex surgeries can be done on these children, all of which are risky. Consequently, some of these children can survive into their twenties, though this will be with severe cognitive deficiencies. The ethical challenge for pediatricians is determining what sort of conversation to have with parents regarding treatment or non-treatment options. In the case discussed, this was complicated by the fact that a representative of a Trisomy-18 support group contacted these parents one day after the birth to “assure” them that they did not have to choose non-treatment. The problem with these support groups is that they tend to be excessively optimistic and do not know the medically relevant and ethically relevant details associated with prospects for a particular infant. This can complicate the conversation that a pediatrician must have with these parents, and can potentially sow the seeds of distrust. What would clearly be the ethically and practically wrong thing to do would be to tell these parents to pay no attention to these support groups. Overall, the discussion in this workshop was lively and thoughtful.

Drs. Eijkholt and Stahl present at International Conference on Clinical Ethics Consultation

Marleen Eijkholt photoDevan Stahl photoCenter faculty members Marleen Eijkholt and Devan Stahl attended and presented at the 14th International Conference on Clinical Ethics Consultation (ICCEC), held June 21-23 in Oxford, England.

Dr. Eijkholt presented as part of a collaborative panel on “Helpfulness in Clinical Ethics Consultation Notes,” which also included Dr. Stahl, Dr. Stella Reiter-Theil, and Dr. Jugen Wallner, who are respectively from Germany and Switzerland. Dr. Eijkholt presented her paper, “An Empirical View on Helpfulness in Clinical Ethics Consultation Notes,” which outlined the data that she had gathered from analyzing case consultation notes from fellow clinical ethicists. She explored the questions: What made their notes helpful? How should clinical ethics consultation (CEC) chart notes be formulated to be most helpful, while being mindful about professional boundaries, and being mindful about the recipients of these notes, i.e. vulnerable health care providers who are not necessarily philosophers? While medical providers are used to reading notes from their fellow consultants in the form of conclusions–such as, “patient is in kidney failure,” “palliative care recommends x dosages of morphine”–ethics consultants hardly ever find themselves faced with a clinical scenario that allows for such “simple” conclusions. Moreover, such authoritarian conclusions are undesirable according to the framework of the clinical ethics profession. CEC recommendations therefore take a different format. After analyzing several notes, Dr. Eijkholt concluded with an acknowledgement of the tension between quality and helpfulness.

Dr. Stahl presented on the panel “Is there a place for clinical ethics consultation outside of the hospital setting?” alongside Kevin Dirksen, Tyler Gibb, and James Hynds. The group discussed models for doing outpatient clinical ethics consultation at their respective hospital settings. Dr. Stahl presented on new efforts here in East Lansing to bridge the inpatient and outpatient settings using ethics consultation handoffs.

Article from Dr. Stahl in ‘AJOB Neuroscience’

Devan Stahl photoCenter Assistant Professor Dr. Devan Stahl and co-author John Banja (Emory University) have a target article in the current issue of AJOB Neuroscience, titled “The Persisting Problem of Precedent Autonomy Among Persons in a Minimally Conscious State: The Limitations of Philosophical Analysis and Clinical Assessment.”

Abstract: Determining whether it is ethical to withdraw life-sustaining treatments (WOLST) from a patient in the minimally conscious state (MCS) recalls recurring debates in bioethics, including the applicability of precedent autonomy and the usefulness of quality-of-life assessments. This article reviews the new clinical understanding of MCS and the complexities involved in detecting covert awareness in patients. Given the diagnostic and prognostic uncertainty surrounding most MCS determinations, we review the ongoing debates concerning precedent autonomy as they apply to making WOLST determinations for patients in MCS. We also consider the moral obligations clinicians might have to understand an MCS patient’s advance directives, current preferences, and quality of life. We argue that an optimal approach for making WOLST determinations requires weighing patients’ previous wishes against their current circumstances but that even here, factual as well as ethical vagaries and disagreements will be relatively commonplace.

The full text is available online via Taylor & Francis Online (MSU Library or other institutional access may be required to view these articles).