Emily Largent

• University of Pennsylvania

Research on caregivers suggests interpersonal contact with persons with Alzheimer’s disease (AD) and higher disease-oriented knowledge may heighten AD stigma, though these same mechanisms are often employed in antistigma campaigns. If we better understand associations among caregiver experience, interpersonal contact, AD knowledge, and AD stigma, w...

Alzheimer’s disease (AD)-focused recruitment research registries can help identify eligible participants for AD studies, but registry participation is limited among racial and ethnic groups most at risk for AD. Using the Reasoned Action Approach (RAA), this study is part of a larger project to design theory-based persuasive recruitment messages tha...

This comment provides an overview of ethical considerations for researchers developing and testing minimal-risk devices that interact or interface with people, such as electronic wearables and biomedical sensors. We outline the process of independent review, emphasizing that research can undergo different levels of review depending on its design an...

Recent arguments in aging and dementia research suggest that “terminal lucidity”—defined as unexpected communication or connectedness occurring shortly before death—is distinct from “paradoxical lucidity”—defined as an episode of communication or connectedness in a person who is assumed to have lost these capacities due to progressive neurodegenera...

Growing interest in embedded research approaches-where research is incorporated into clinical care-has spurred numerous studies to generate knowledge relevant to the real-world needs of patients and other stakeholders. However, it also has presented ethical challenges. An emerging challenge is how to understand the nature and extent of investigator...

Alzheimer’s disease (AD) causes progressive disability and, ultimately, death. Currently no therapy can delay or slow cognitive and functional decline. This prognosis contributes to the general public’s negative reactions—discrimination, pity, and social distance—toward individuals with AD and their families. But what if, using AD biomarker tests,...

Paradoxical lucidity in dementia is a clinically significant but understudied phenomenon. A provisional definition was proposed by the 2018 National Institute on Aging expert workshop and published in Alzheimer's and Dementia. However, several conceptual features of this definition remain vague, creating barriers to robust clinical research. Here,...

Background/objectives: Disclosure of Alzheimer's disease (AD) risk information to cognitively unimpaired older adults may become more common if preclinical AD is shown to be identifiable and amenable to treatment. Little, however, is known about how families will react to this information. Design and setting: Semi-structured telephonic interview...

Several large clinical trials are underway to discover therapies to delay or prevent the onset of dementia caused by Alzheimer’s disease (AD). A common feature of these trials is that they are testing therapies in people who do not yet have changes in memory or thinking—that is, who are cognitively unimpaired—but who have a biologically defined ris...

Importance As COVID-19 vaccine distribution continues, policy makers are struggling to decide which groups should be prioritized for vaccination. Objective To assess US adults’ preferences regarding COVID-19 vaccine prioritization. Design, Setting, and Participants This survey study involved 2 independent, online surveys of US adults aged 18 year...

Research that is integrated into ongoing clinical activities holds the potential to accelerate the generation of knowledge to improve the health of individuals and populations. Yet integrating research into clinical care presents difficult ethical and regulatory challenges, including how or whether to obtain informed consent. Multiple empirical stu...

To prepare for potential human infection challenge studies (HICS) involving SARS-CoV-2, we convened a multidisciplinary working group to address ethical questions regarding whether and how much SARS-CoV-2 HICS participants should be paid. Because the goals of paying HICS participants, as well as the relevant ethical concerns, are the same as those...

Delivery of high-quality end-of-life care—care that both increases the likelihood of desired outcomes and is consistent with current professional knowledge—to persons with dementia is fraught with challenges. Among these, a key challenge is the need for early and ongoing decision-making. Due to progressive cognitive and functional decline, persons...

Recent studies suggest blood levels of phosphorylated tau (p-tau) isoforms can detect both the tau and amyloid pathologies that define Alzheimer disease (AD).¹ More research is needed to replicate these results in large, diverse cohorts and quantify a p-tau blood test’s ability to prognosticate the onset of dementia. Nevertheless, we anticipate tha...

This article argues that supported decision making is ideal for people with dynamic cogni-tive and functional impairments that place them at the margins of autonomy. First, we argue that guardianship and similar surrogate decision-making frameworks may be inappropriate for people with dynamic impairments. Second, we provide a conceptual foundation...

Background As a result of caring for a person with dementia, caregivers of persons with Alzheimer’s disease (AD) may be uniquely aware of public stigma for persons with AD. Objective The purpose of this study was to compare self-identified caregivers and non-caregivers’ expectations of public stigma experienced by persons living with dementia. Me...

This survey study assesses the acceptability of coronavirus disease 2019 (COVID-19) vaccine mandates among members of the US public.

Many studies show that caregivers for those with Alzheimer’s Disease (AD) are disproportionately female, but few studies have investigated how public attitudes influence this gender disparity. We analyzed secondary data from an experimental study of public reactions to AD dementia. Analysis included 944 respondents who read a vignette about a man w...

The COVID-19 pandemic poses distinct challenges for the conduct of minimal-risk clinical research, including the very definition of minimal risk, the heterogeneity of risk among potential study participants, privacy concerns, and practical issues in recruitment and written informed consent.

Background Studies of persons with Alzheimer’s disease (AD) and related dementias typically require “study partners” (SPs) to report on the subject’s wellbeing and function. But little is known about how who a SP is might impact on these reports. Knowing this may help inform the interpretation of AD research. Methods We analyzed data from 730 olde...

Background Studies of persons with Alzheimer’s disease (AD) and related dementias typically include “study partners” (SPs) who report on participants’ wellbeing and function. But little is known about what factors predict the type of person who steps into the role. Knowing this will inform barriers to recruitment into AD research. It may also offer...

Background Alzheimer’s disease (AD) secondary prevention trials typically require cognitively unimpaired individuals to learn the results of an amyloid PET scan. Additionally, they are required to enroll with a study partner who serves as a knowledgeable informant and often learns the participant’s amyloid PET scan result. The purpose of this study...

Background When and how to communicate effectively the results of genetic and biomarker based prediction, detection, and quantification of the brain substrates of dementia involve important ethical and legal issues critical for precision medicine. The urgency of the issue has increased as People Living with Dementia (PLwD) and with Risk for Dementi...

Background Alzheimer’s disease (AD) clinical trials, even trials recruiting cognitively normal populations, require participants to enroll with a “study partner” (SP). SPs serve as knowledgeable informants, reporting on participants’ cognitive and functional performance. The SP requirement can be a barrier to research participation, especially if a...

A primary goal of our medical education system is to produce physicians qualified to promote health, prevent and treat disease, and relieve suffering. Although some aspects of the practice of medicine can be learned in classrooms, from textbooks, or with simulators, other aspects can only be learned through the direct provision of patient care. Res...

Clinical research is critical to combatting COVID-19, but regulatory requirements for human subjects protection may sometimes pose a challenge in pandemic circumstances. Although regulators have offered some helpful guidance for research during the pandemic, we identify further compliance challenges regarding institutional review board (IRB) review...

Embedded pragmatic clinical trials (ePCTs) present an opportunity to improve care for people living with dementia (PLWD) and their care partners, but they also generate a complex constellation of ethical and regulatory challenges. These challenges begin with participant identification. Interventions may be delivered in ways that make it difficult t...

A variety of trials are in development and underway to examine potential interventions for the treatment and prophylaxis of novel coronavirus disease 2019 (COVID-19). How should we think about offering payment to participants in these trials? Payment for research participation is ethically contentious even under ideal circumstances, and pandemics a...

Cambridge Core - Medical Law, Ethics and forensic Medicine - Disability, Health, Law, and Bioethics - edited by I. Glenn Cohen

Importance Clinical guidelines currently recommend against amyloid imaging for cognitively unimpaired persons. The goal of Alzheimer’s disease (AD) prevention, together with advances in understanding the pathophysiology of AD, however, has led to trials testing drugs in cognitively unimpaired persons who show evidence of AD biomarkers. Assuming the...

Early on the morning of March 21, 2019, Nancy Childs awoke and, as is her habit, began scrolling through her news feed. There was bad news for her and her husband, Mike. Biogen and Eisai had abruptly halted their phase III trial of aducanumab to slow cognitive and functional impairment in persons with mild cognitive impairment (MCI) or dementia cau...

Offering payment is an important means of facilitating research participation. Yet, offers of payment raise ethical challenges that may be heightened when prospective participants suffer from or are at risk for opioid use disorder (OUD). We surveyed principal investigators (PIs) conducting research in this population to characterize the relative im...

In this issue of the Hastings Center Report, James Sabin and his colleagues ask what responsibility investigators in a learning health organization have to patients when research—particularly research of which patients might be unaware—illuminates problematic aspects of the patients' care. Sabin and his colleagues were confronted by this question i...

The problem of insufficient recruitment to clinical oncology trials is well-known. Some stakeholders view mobile apps as a solution with the potential to make recruitment more efficient, to lower trial costs, to support patient-centeredness, and to accelerate treatment advances. Recruitment and trial-finding apps seek to disrupt the traditional app...

Seven states have legalized physician-assisted death (PAD) for competent, terminally ill individuals; these criteria exclude persons with dementia (PWD). However, there is ethical and policy discussion around expanding access to PAD to people with Alzheimer disease (AD).¹,2 Here, we present attitudes toward PAD of cognitively normal individuals enr...

Classic statements of research ethics advise against permitting physician-investigators to obtain consent for research participation from patients with whom they have preexisting treatment relationships. Reluctance about “dual-role” consent reflects the view that distinct normative commitments govern physician–patient and investigator–participant r...

A couple recently came to our memory center for a research visit. The husband is a participant in a clinical trial evaluating the efficacy of a drug to prevent the onset of dementia in cognitively unimpaired persons with elevated brain amyloid, an Alzheimer disease (AD) biomarker. In the course of the visit, the man’s wife—who is also his study par...

Recognising that offers of payment to research participants can serve various purposes—reimbursement, compensation and incentive—helps uncover differences between participants, which can justify differential payment of participants within the same study. Participants with different study-related expenses will need different amounts of reimbursement...

Importance Offers of payment for research participation are ubiquitous but may lead prospective participants to deceive about eligibility, jeopardizing study integrity and participant protection. To date, neither the rate of payment-induced deception nor the influence of payment amount has been systematically studied in a nationally representative...

Attrition is a serious problem in many clinical trials. The practice of offering completion bonuses—financial incentives offered to participants on the condition that they remain in a trial until they reach a prespecified study endpoint—is one means of addressing attrition. Despite their practical appeal, however, completion bonuses remain ethicall...

Background: Global leaders have set an ambitious goal of developing interventions to effectively treat or prevent Alzheimer's disease by 2025. Case presentation: Achieving this goal will require clinical trials to test promising interventions, yet Alzheimer's researchers are confronting a clinical trial recruitment crisis. One reason for this is...

Many foreign parents bring their children to the United States for medical treatments that are unavailable in their own country. Often, however, parents cannot afford expensive treatments. Doctors and hospitals then face a dilemma. Is it ethically permissible to consider the patient's citizenship and ability to pay? In this Ethics Rounds, we presen...

Social media communication among clinical trial participants has the potential to pose risks to their safety and to trial integrity. The Social Media ADEPT framework may help mitigate that potential by encouraging investigators and patient partners to work together to Assess social media risks, Design studies to minimize those risks, Educate partic...

A key aim of patient-centered outcomes research (PCOR) is to generate data that are important to patients by deliberately and extensively involving them in all aspects of research, from design to dissemination. However, certain elements of PCOR raise challenging and potentially novel ethical and regulatory issues for institutional review boards and...

To ensure that the information resulting from research is relevant to patients, the Patient‐Centered Outcomes Research Institute eschews the “traditional health research” paradigm, in which investigators drive all aspects of research, in favor of one in which patients assume the role of research partner. If we accept the premise that patient engage...

Patient-centered outcomes research (PCOR) is becoming increasingly common. However, there is little evidence regarding what novel ethical challenges, if any, are posed by PCOR with relevance to institutional review board (IRB) oversight and human subjects protections. This article reports the results of a national survey of all IRB chairpersons fro...

Shortfalls in clinical trial recruitment and retention constitute a major obstacle to scientific advancement.¹ One means of increasing patient participation rates is to reduce associated financial burdens. In several states, efforts are under way to achieve this goal for patients in cancer clinical trials through legislation explicitly allowing rei...

The practice of paying research participants has received significant attention in the bioethics literature, but the focus has been almost exclusively on consideration of factors relevant to determining acceptable payment amounts. Surprisingly little attention has been paid to what happens once the payment amount is set. What are the ethical parame...

The authors propose a framework for evaluating the appropriateness of payments to research participants. They distinguish three acceptable rationales for payment: out-of-pocket expenses, time and burdens of participation, and incentive to participate.

Public access to clinical trial consent forms, beyond those individuals involved in reviewing, conducting, or participating in a trial, has been notoriously poor, resulting in missed opportunities for empirical analysis and improvement, among other benefits. However, recent changes to the Common Rule and policies governing ClinicalTrials.gov promis...

The practice of offering payment to individuals in exchange for their participation in clinical research is widespread and longstanding. Nevertheless, such payment remains the source of substantial debate, in particular about whether or the extent to which offers of payment coerce and/or unduly induce individuals to participate. Yet, the various la...

The peer review process is central to the advancement of scholarly knowledge and is vital to the advancement of individual careers. With so much at stake, it is important to examine, and reexamine, issues pertaining to the fairness and quality of peer review on an ongoing basis. One central issue is blinding. In this chapter, we review evidence fro...

In 2014, West Africa confronted the most severe outbreak of Ebola virus disease (EVD) in history. At the onset of the outbreak—as now—there were no therapies approved by the U.S. Food and Drug Administration (FDA) for prevention of, post-exposure prophylaxis against, or treatment of EVD. As a result, the outbreak spurred interest in developing nove...

HIV cure research holds great potential to eradicate HIV, but the benefit to early trial participants is likely to be small. Moreover, participation carries unknown and possibly significant risks to research participants. This is the risk:benefit ratio challenge of HIV cure research. Although it may be consensual and rational for individuals to par...

Administrators sometimes face ethical dilemmas about the allocation of institutional resources. One such situation is when elective surgery cases require reserved ICU beds and the ICU is full. Such situations arise frequently in children's hospitals today. They are sometimes complicated by questions about whether every patient in the ICU belongs th...

Disasters typically do not allow time for prolonged moral reflection or ethical deliberation; yet, clinicians who volunteer in the wake of disasters routinely encounter ethical challenges, sometimes accompanied by mental anguish and moral distress. While accounts of these challenges are often shared with fellow clinicians, they have entered the eth...

We argued last year in this journal that extensive integration of research and care is a worthy goal of health system design, and we second the call from Ruth Faden and colleagues to move toward learning health care systems. As they recognize, learning health care systems demand the coordination of research and medical ethics—two sets of normative...

Payment to recruit research subjects is a common practice but raises ethical concerns relating to the potential for coercion or undue influence. We conducted the first national study of IRB members and human subjects protection professionals to explore attitudes as to whether and why payment of research participants constitutes coercion or undue in...

The rule of rescue describes the moral impulse to save identifiable lives in immediate danger at any expense. Think of the extremes taken to rescue a small child who has fallen down a well, a woman pinned beneath the rubble of an earthquake, or a submarine crew trapped on the ocean floor. No effort is deemed too great. Yet should this same moral in...

Medical ethics assumes a clear boundary between clinical research and clinical medicine: one produces knowledge for the benefit of future patients, while the other provides optimal care to individuals right now. It also assumes that the two cannot be integrated without sacrificing the needs of the current patient to those of future patients. But in...

America's present level of health care spending is unsustainable. The rising costs of health care would be less concerning if there was evidence suggesting that more spending made Americans healthier; the evidence, however, suggests otherwise. The purpose of this article is to describe one tool that can potentially address quality and cost concerns...

Emergency research poses a fundamental ethical dilemma: prohibit valuable research because informed consent is not possible or enroll individuals in clinical trials without informed consent. Although emergency research without initial consent is allowable in the United States, its regulatory status remains uncertain internationally. More important,...

Following US Food and Drug Administration (FDA) approval, clinicians may lawfully prescribe a drug or biologic agent for treatment regimens not specified in the approved labeling or package insert. This is known as off-label use. A recent study1 found that for 160 common drugs in the United States, off-label use accounted for 21% of all prescriptio...