About

Emily Largent, JD, PhD, RN, is the Emanuel and Robert Hart Associate Professor of Medical Ethics and Health Policy and the Chief of the Division of Medical Ethics at Penn. She holds a secondary appointment at Penn Law, is a Senior Fellow at the Leonard Davis Institute of Health Economics, and is affiliated with the Center for Health Incentives and Behavioral Economics. Her work explores ethical and regulatory aspects of human subjects research as well as the social, legal, and ethical considerations that arise when research findings are translated into care, with a particular focus on neurodegenerative diseases, including Alzheimer’s disease. Her research is supported by grant awards from the National Institute on Aging, and she is a member of the Greenwall Faculty Scholars Program Class of 2023. Dr. Largent was the 2023 recipient of the Baruch A. Brody Award & Lecture in Bioethics and is an elected fellow of the Hastings Center. She has been published in leading bioethics and biomedical journals such as The Hastings Center Report, American Journal of Bioethics, New England Journal of Medicine, and JAMA. Her academic background includes a BSN from the University of Pennsylvania School of Nursing, a BSFS from Georgetown University, a JD from Harvard Law School, and a PhD in Health Policy with a concentration in ethics from Harvard University. She previously served as a fellow in the Department of Bioethics at the National Institutes of Health and clerked for Chief Judge Jeffrey Howard of the United States Court of Appeals for the First Circuit.

Research topics

• Medicine
• Political Science
• Psychology
• Pathology
• Business
• Law
• Virology
• Economics
• Internal medicine
• Engineering ethics
• Public relations
• Engineering
• Criminology
• Actuarial science
• Public economics
• Nuclear medicine
• Environmental health
• Family medicine
• Economic growth
• Biology
• Psychiatry
• Intensive care medicine
• Genetics
• Nursing

Selected publications

• Towards cascading genetic risk in Alzheimer’s disease

  Brain · 2024 · 11 citations

  • Oncology
  • Internal medicine
  • Medicine

  Alzheimer's disease typically progresses in stages, which have been defined by the presence of disease-specific biomarkers: amyloid (A), tau (T) and neurodegeneration (N). This progression of biomarkers has been condensed into the ATN framework, in which each of the biomarkers can be either positive (+) or negative (-). Over the past decades, genome-wide association studies have implicated ∼90 different loci involved with the development of late-onset Alzheimer's disease. Here, we investigate whether genetic risk for Alzheimer's disease contributes equally to the progression in different disease stages or whether it exhibits a stage-dependent effect. Amyloid (A) and tau (T) status was defined using a combination of available PET and CSF biomarkers in the Alzheimer's Disease Neuroimaging Initiative cohort. In 312 participants with biomarker-confirmed A-T- status, we used Cox proportional hazards models to estimate the contribution of APOE and polygenic risk scores (beyond APOE) to convert to A+T- status (65 conversions). Furthermore, we repeated the analysis in 290 participants with A+T- status and investigated the genetic contribution to conversion to A+T+ (45 conversions). Both survival analyses were adjusted for age, sex and years of education. For progression from A-T- to A+T-, APOE-e4 burden showed a significant effect [hazard ratio (HR) = 2.88; 95% confidence interval (CI): 1.70-4.89; P < 0.001], whereas polygenic risk did not (HR = 1.09; 95% CI: 0.84-1.42; P = 0.53). Conversely, for the transition from A+T- to A+T+, the contribution of APOE-e4 burden was reduced (HR = 1.62; 95% CI: 1.05-2.51; P = 0.031), whereas the polygenic risk showed an increased contribution (HR = 1.73; 95% CI: 1.27-2.36; P < 0.001). The marginal APOE effect was driven by e4 homozygotes (HR = 2.58; 95% CI: 1.05-6.35; P = 0.039) as opposed to e4 heterozygotes (HR = 1.74; 95% CI: 0.87-3.49; P = 0.12). The genetic risk for late-onset Alzheimer's disease unfolds in a disease stage-dependent fashion. A better understanding of the interplay between disease stage and genetic risk can lead to a more mechanistic understanding of the transition between ATN stages and a better understanding of the molecular processes leading to Alzheimer's disease, in addition to opening therapeutic windows for targeted interventions.

  DOI

• What is paradoxical lucidity? The answer begins with its definition

  Alzheimer s & Dementia · 2021 · 29 citations

  • Psychology
  • Epistemology
  • Cognitive science

  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, we critically analyze the provisional definition and present a refined definition that can be applied in clinical research. The refined definition is based on an analytic process our research group recently undertook to operationalize paradoxical lucidity for our own study protocol. Our goal is to facilitate debate and potentially harmonize interpretations of paradoxical lucidity among research groups.

  DOI

• Incorporating Health Equity Into COVID-19 Reopening Plans: Policy Experimentation in California

  American Journal of Public Health · 2021 · 18 citations

  1st authorCorresponding
  • Political Science
  • Business
  • Public economics

  California has focused on health equity in the state's COVID-19 reopening plan. The Blueprint for a Safer Economy assigns each of California's 58 counties into 1 of 4 tiers based on 2 metrics: test positivity rate and adjusted case rate. To advance to the next less-restrictive tier, counties must meet that tier's test positivity and adjusted case rate thresholds. In addition, counties must have a plan for targeted investments within disadvantaged communities, and counties with more than 106 000 residents must meet an equity metric. California's explicit incorporation of health equity into its reopening plan underscores the interrelated fate of its residents during the COVID-19 pandemic and creates incentives for action. This article evaluates the benefits and challenges of this novel health equity focus, and outlines recommendations for other US states to address disparities in their reopening plans.

  PublisherOA PDFDOI

• Promoting Ethical Payment in Human Infection Challenge Studies

  The American Journal of Bioethics · 2021 · 66 citations

  Senior authorCorresponding
  • Political Science
  • Psychology
  • Business

  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 arising for other types of clinical research, the same basic framework for ethical payment can apply. This framework divides payment into reimbursement, compensation, and incentives, focusing on fairness and promoting adequate recruitment and retention as counterweights to concerns about undue inducement. Within the basic framework, several factors are especially salient for HICS, and for SARS-CoV-2 HICS in particular, including the nature of participant confinement, anticipated discomfort, risks and uncertainty, participant motivations, and trust. These factors are reflected in a payment worksheet created to help sponsors, researchers, and ethics reviewers systematically develop and assess ethically justifiable payment amounts.

  DOI

• Problems With Paying People to Be Vaccinated Against COVID-19

  JAMA · 2021 · 79 citations

  1st authorCorresponding
  • Medicine
  • Virology
  • Intensive care medicine

  This Viewpoint describes features of 2 proposals to pay US residents to be vaccinated against COVID-19 and proposes ethical and practical complications of the plans, arguing that they are morally suspect, likely unnecessary, and may be counterproductive.

  DOI

• Cognitively unimpaired adults’ reactions to disclosure of amyloid PET scan results

  PLoS ONE · 2020 · 102 citations

  1st authorCorresponding
  • Medicine
  • Pathology
  • Nuclear medicine

  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 eventual success of such trials, millions of patients will be affected. There is a need to understand the effects of biomarker disclosure on those individuals. DESIGN: The Study of Knowledge and Reactions to Amyloid Testing (SOKRATES) involved 2 semi-structured telephone interviews with individuals who received amyloid PET scan results as part of screening for research participation. Post-disclosure interviews were conducted at 4 to 12 weeks and again 1 year later. Data were collected from November 5, 2014 to November 30, 2016. Interviews were transcribed and coded in NVivo 12.0. PARTICIPANTS: 80 adults aged 65 and older: 50 who received "elevated" and 30 who received "not-elevated" amyloid PET scan results. MAIN OUTCOMES: Interviews examined four domains: (1) comprehension of the amyloid PET scan result; (2) implications of the result for sense of self, memory, and future; (3) sharing of results with others; and (4) AD risk-reduction behaviors. RESULTS: Participants who received an elevated amyloid PET scan result viewed the result as more serious and sensitive than other medical test results given its unique implications for identity, self-determination, and stigma. In contrast, participants who received a not-elevated amyloid PET scan result described feeling relief and reinterpreted perceived memory impairments as normal aging. Participants with elevated amyloid reported contemplating and making more changes to health behaviors and future plans than their peers with not-elevated amyloid. CONCLUSIONS: Clinical practice in the diagnosis and treatment of persons with preclinical AD, a stage of the disease defined by the presence of biomarkers in the absence of cognitive impairment, will need to address matters of identity, stigma, and life-planning.

  DOI

• Regulatory flexibility for COVID-19 research

  Journal of Law and the Biosciences · 2020 · 50 citations

  Senior authorCorresponding
  • Political Science
  • Political Science
  • Medicine

  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 and approval, informed consent, emergency research, and research involving incarcerated people. Our proposals for regulatory flexibility in these areas seek to satisfy the goals of protecting participants and promoting the development of high-quality evidence to improve patient care. These recommendations may have relevance beyond the COVID-19 pandemic to enhance the efficiency of research oversight and participant protection more broadly.

  DOI

• US Public Attitudes Toward COVID-19 Vaccine Mandates

  JAMA Network Open · 2020 · 154 citations

  1st authorCorresponding
  • Family medicine
  • Virology
  • Psychology

  Ending the coronavirus disease 2019 (COVID-19) pandemic through vaccination will require sufficient uptake, possibly through mandatory vaccination. At present, certain vaccines are required for children to attend school. Although vaccine mandates for adults are legal, they have generally been applied narrowly to select groups, such as health care workers, rather than broadly enforced. We surveyed the US public to assess acceptability of COVID-19 vaccine mandates.

  DOI

Recent grants

• UNDERSTANDING HOW THE STUDY PARTNER REQUIREMENT IMPACTS THE DISCOVERY AND TRANSLATION OF PRECLINICAL ALZHEIMERS DISEASE

  NIH · $637k · 2019–2024

Frequent coauthors

• Jason Karlawish

  California University of Pennsylvania

  52 shared

• Kristin Harkins

  University of Pennsylvania

  43 shared

• Holly Fernandez Lynch

  Philadelphia University

  41 shared

• Shana D. Stites

  University of Pennsylvania

  27 shared

• Govind Persad

  University of Bergen

  25 shared

• Andrew Peterson

  17 shared

• Monica E. Peek

  University of Chicago

  16 shared

• Michelle M. Mello

  Stanford University

  16 shared

Education

• B.S., Science, Technology, and International Affairs

  Georgetown University

• M.S., Nursing

  Penn Nursing

• Ph.D., Health Policy

  Harvard University

• Other

  Harvard Law School

Awards & honors

• Greenwall Faculty Scholars Program Class of 2023
• Baruch A. Brody Award & Lecture in Bioethics (2023)
• Fellow of the Hastings Center

Similar researchers at University of Pennsylvania

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• Craig B. Thompsonh-277
• Daniel J Raderh-236
• Carl H. Juneh-218
• M. Celeste Simonh-185