Videos

Recently, the U.S. Food and Drug Administration (FDA) has been placing greater emphasis and implementing reforms focused on improving health equity. The focus of the reforms has been largely on increasing representation in clinical trials, enhancing transparency and access to available data on the effect of medical products on minority populations, and promoting health and safety communication to these populations.  Concurrently, FDA continues to increasingly adopt regulatory flexibility in their review process, accepting less rigorous evidence as the basis of approval of novel medical products. In the case of accelerated approval, the agency allows for residual uncertainty at the time of approval, but then requires sponsors to complete additional studies that confirm clinical benefit in a timely manner; should these not be completed or if the studies yield negative results, FDA can withdraw these drugs from the market. However, the expanded and more flexible use of this pathway by the FDA has raised questions about which communities will bear the burden of such uncertainty and whether this may in fact exacerbate health disparities.

In this presentation, Dr. Ramachandran will discuss trends in FDA’s adoption of regulatory flexibility in the approval of novel medical predicts, the implication of such policies, and proposals to center health equity in regulatory decision-making.

Reshma Ramachandran, MD, MPP, MHS
Assistant Professor of Medicine
Yale School of Medicine

Clinical care has long treated young adults similarly to their older counterparts, despite mounting evidence that young adults experience different outcomes. As such, the momentum to increase diversity in clinical trials should ensure the inclusion and analysis of adolescents and young adult patients.

By increasing the representation of young adults in clinical trials, we can improve their outcomes and work towards creating a more equitable healthcare system. The lack of adequate subgroup analysis especially when looking at systems such as the FDA Adverse Event Reporting System exacerbates the issue. Additionally, by including young adults in the drug development process, we can gain a better understanding of the unique challenges they face and tailor treatments accordingly.

Sneha Dave
Executive Director and Founder
Generation Patient

How public policy, structural racism, and law enforcement affect the clinical care for survivors of violence, and what opportunities clinicians and healthcare systems have to prevent individual and structural violence.

Elinore J. Kaufman, MD MSHP
Assistant Professor of Surgery, Division of Traumatology
Surgical Critical Care and Emergency Surgery
Perelman School of Medicine
University of Pennsylvania

Against the backdrop of mental health crises and widespread diseases of despair, psychedelic drugs have emerged as promising treatments for several psychiatric conditions including severe depression, anxiety, post-traumatic stress disorder, suicide, and addiction. In this talk, I will describe ethical and professional challenges that, unless addressed, will expose participants (and eventually patients) to unnecessary risk and will undermine scientific progress. These include questions related to obtaining informed consent for transformative experiences and the protection of vulnerable persons in non-ordinary states. I will offer recommendations for policy and professionalism to advance ethical research in this emerging field.

Dominic Sisti, PhD
Associate Professor of Medical Ethics & Health Policy
Associate Professor of Psychiatry
Associate Professor of Philosophy
Perelman School of Medicine, University of Pennsylvania
Director, Scattergood Program for Applied Ethics in Behavioral Health Care

Structural racism has been described as a fundamental cause of health, operating through multiple, replaceable mechanisms to generate persistent disadvantage. This view implies that interventions to durably reduce structurally-mediated racial disparities in health requires intervening on multiple mechanisms at once. This talk describes the IGNITE study, which uses a cluster randomized trial to test an unprecedented, “big push” effort to improve health outcomes in predominantly Black communities in Philadelphia.

Atheendar Venkataramani, MD, PhD
Assistant Professor of Medical Ethics and Health Policy
Assistant Professor of Medicine
Director of the Opportunity for Health Lab
Perelman School of Medicine, University of Pennsylvania

The COVID-19 pandemic has exposed numerous unresolved research ethics challenges, particularly for Data Monitoring Committees (DMCs). DMCs have long faced high stakes decisions in clinical trials including whether to continue, modify, or terminate a trial based on emerging trial data. In the COVID pandemic, DMCs have been called “unsung heroes” for their work to ensure the ongoing value of research amid rapidly-changing circumstances and great pressure to release early findings to the public. Yet unlike other research oversight bodies, such as Institutional Review Boards, DMCs have limited formal ethical guidance. For example, should DMCs ensure the accuracy of press releases detailing study findings? Do DMCs consider when to unblind participants after a study is over if it is relevant for their future medical decision-making? In this presentation, I will examine ethical challenges that are often implicitly addressed in DMC decision-making. I will report preliminary results of a qualitative study of DMC members (i.e., statisticians, clinicians, and ethicists) and highlight persistent controversies about the roles that DMCs should play. Finally, I will explore whether and how bioethicists can help address the complex ethical challenges that arise for DMCs.

Seema K. Shah, JD
Associate Professor in Pediatrics at Northwestern University Medical School; Founder’s Board Professor of Medical Ethics
Associate Director of Research Ethics at Lurie Children’s Hospital

June 6, 2022 - Hosted by the Department of Medical Ethics
Belmont’s Third Pillar: Towards Justice in Clinical Research

June 7, 2022 - Hosted by the Abramson Cancer Control Program
The Challenge of Quantifiable Research Representation

AIDS activists in the 1980s descended on the FDA in protest claiming the agency was killing them by delaying approval of promising AIDS drugs. The truth turned out to be more complicated as the first generation of antiretroviral drugs was far from promising leading to years of uncertainty about their clinical effects. Activists pioneered new mechanisms to ensure access to new drugs for AIDS, but also proposals to garner the necessary evidence to guide their optimal use. By the early 1990s, activists were pushing for the FDA to get tougher on companies and confirmatory studies under accelerated approval, but Pandora’s box had already been opened leading to decades of faster and faster drug approvals with less and less evidence about their effectiveness.

Gregg Gonsalves, PhD
Associate Professor of Epidemiology (Microbial Diseases)
Affiliated Faculty, Program in Addiction Medicine
Associate (Adjunct) Professor of Law, Yale Law School
Co-Director, Global Health Justice Partnership
Co-Director, Collaboration for Research Integrity and Transparency
 

The 3Rs serve as a universal touchstone, with respect to refinement, reduction, and replacement, for veterinary staff, ethical review committees and scientists. Russell and Burch established these terms as part of a new applied science in 1959, aiming to improve animal welfare using application of the 3Rs as a development tool for scientific methodology. In consideration of animal use, the anticipated benefits of scientific inquiry are to be balanced against the potential impacts borne by the animals themselves; this ethical calculation is referred to as the ‘harm-benefit’ analysis. Over time, rigid interpretations of the classic 3Rs in study design (refinement), statistical analysis (reduction), and selection of alternatives to live animals (replacement) have stifled the spirit of their initial intent and limited scientific progress and production of translatable and reproducible results. The exquisiteness of the 3Rs is that much like classical artwork, they are inherently subject to broad interpretation across the contemporary biomedical community. Reconsidering the classic 3Rs with progressive interpretations, in combination with other ethical tools of analysis and validity assessments, is essential for ongoing intricate considerations of appropriate and future animal use.

F. Claire Hankenson, DVM, MS, DACLAM
Associate Vice Provost for Research
Executive Director of University Laboratory Animal Resources (ULAR) & Attending Veterinarian
Professor of Laboratory Animal Medicine, Dept of Pathobiology; School of Veterinary Medicine, University of Pennsylvania

Implementation science is the study of methods to increase the use of evidence-based practices in routine clinical care and to reduce the research-to-practice gap. Implementation science has a set of distinct foci including stakeholder engagement, characterization of contextual factors at the patient- (e.g., preferences), clinician- (e.g., knowledge), and organizational- (e.g., leadership) level, and measurement of implementation outcomes. Because of the primary emphasis on intervention delivery and scale-up, this research generates distinct ethical considerations. We use ASPIRE, a type III hybrid effectiveness trial of strategies to implement firearm safety promotion as a universal suicide prevention strategy in pediatric primary care, as a case exemplar to investigate salient ethical issues that may arise during implementation research. Using examples from ASPIRE, we examine (1) pragmatic tradeoffs (e.g., acceptability and effectiveness) in study design and execution; (2) sustainability and health system integration as up-front considerations; and (3) unintended consequences with implications for health equity. We also identify other ripe ethical topics for further exploration within implementation research, including evidence for the research-to-practice gap, power dynamics and stakeholder engagement, and contextual equipoise (i.e., genuine uncertainty about the contextual conditions in which implementation will be effective). In conclusion, we will highlight future directions for empirical work at the intersection of bioethics and implementation science.

Rinad Beidas, PhD
Professor, Psychiatry, Medical Ethics and Health Policy, and Medicine, Perelman School of Medicine; Director, Penn Implementation Science Center (PISCE@LDI), Leonard Davis Institute; Director, Penn Medicine Nudge Unit

Katelin Hoskins, PhD, MBE, CRNP
NIMH T32 Postdoctoral Fellow, Center for Mental Health, Department of Psychiatry, Perelman School of Medicine; Associate Fellow, Leonard Davis Institute of Health Economics, University of Pennsylvania

Prospective informed consent is sometimes not feasible in emergency medical research due to patient incapacitation, short therapeutic windows, and the unavailability of surrogates. In 1996, the U.S. Food and Drug Administration (FDA) established the exception from informed consent (EFIC) regulatory pathway, which allows trials of emergency medical interventions to proceed without prospective consent so long as researchers fulfill an array of pre- and post-study requirements. The most substantial of these requirements is ‘community consultation.’ Ostensibly a substitute for individual consent, community consultation requires researchers to solicit public concerns about their trials and report them to the institutional review board before obtaining approval. However, there has been considerable uncertainty among EFIC investigators about the methods and goals of community consultation. Drawing on interviews with EFIC investigators and my own ongoing involvement in a community consultation process, this talk will critically reflect on what EFIC regulation is accomplishing 25 years after its establishment.

Justin Clapp, PhD, MPH
Assistant Professor, Anesthesiology & Critical Care and Medical Ethics & Health Policy, Perelman School of Medicine
Associated Faculty, Anthropology, School of Arts and Sciences

Curative therapies are available to patients with sickle cell disease both clinically and experimentally. However, the barriers to “universal” accessibility for all patients are vast. In addition to traditional barriers to novel and experimental therapies, a long history of mistrust, stigma and disparities plagues this marginalized patient population. We will address research ethics and policy issues that may impact patients’ decisions to pursue curative therapies.

Kim Smith-Whitley, MD
Executive Vice President and Head of Research and Development Global Blood Therapeutics
Attending Physician, Division of Hematology
Former Director Comprehensive Sickle Cell Center, Children's Hospital of Philadelphia Professor of Pediatrics, Perelman School of Medicine

For decades, providing patients with financial incentives for research participation has been controversial and variably regulated due to uncertainty regarding whether financial incentives serve as undue inducements by blunting peoples’ sensitivity to research risks, or unjust inducements by preferentially increasing enrollment among disadvantaged persons. Emerging normative analyses and a small number of empirical studies of how hypothetical offers of payments influence trial enrollment decisions have increasingly suggested that concerns with incentivizing research may be overblown. But without evidence of how real incentives influence participation in real trials, investigators, research sponsors, and regulatory bodies have rarely modified their practices or norms. This year, we published the results of two randomized trials of real incentives for participating in two real parent trials. This talk will review these trials’ designs and results, interpret these findings in the context of prior knowledge and theory, and identify the remaining unanswered questions.

Scott Halpern, MD, PhD, M.Bioethics
John M. Eisenberg Professor of Medicine, Epidemiology,
Medical Ethics and Health Policy

On the morning of June 7, 2021, the idea of using a positron emission tomography (PET) measure of beta-amyloid as a surrogate for the care of patients with Alzheimer disease was an important hypothesis in need of more research. By the evening of June 7, it was clinical practice. 

This revolution in care was the aftermath of not a scientific breakthrough but the imperious decision of a divided Food and Drug Administration (FDA). The FDA had approved Biogen’s drug aducanumab for the treatment of Alzheimer disease. The agency argued that the drug’s ability to reduce beta-amyloid is an adequate surrogate for clinical benefit. Jason Karlawish will discuss why this controversial decision continues to reverberate throughout the American health care system. It has exposed enduring controversies in developing treatments for brain diseases, the steady breakdown in processes at FDA, the need to revisit why we even have an FDA, and how, in America, a disease does not fully exist until it has a business model.

Jason Karlawish, MD
Professor of Medicine, Medical Ethics and Health Policy, and Neurology, and Co-Director, Penn Memory Center, Perelman School of Medicine, University of Pennsylvania

Dr. Carmen Guerra is the Ruth C. and Raymond G. Perelman Associate Professor of Medicine and the Associate Director of Diversity and Outreach at the Abramson Cancer Center.  Dr. Guerra leads the Abramson Cancer Center’s community engaged efforts to increase participation by underrepresented minorities in cancer clinical trials. In this talk, Dr. Guerra will review the underrepresentation of Black patients on cancer clinical trials, the barriers to participation and how the Abramson Cancer Center has increased participation by Black patients in cancer treatment trials.

Carmen Guerra, M.D., M.S.C.E., F.A.C.P.
Ruth C. and Raymond G. Perelman Associate Professor
Vice Chair of Diversity and Inclusion, Department of Medicine
Associate Director of Diversity and Outreach, Abramson Cancer Center
Advisory Dean, Dr. Helen O. Dickens House, PSOM

Dr. Haresh Kirpalani is Emeritus Professor on the pediatrics faculty at CHOP and McMaster University in Canada. He has been pursuing randomized trial evaluation of common therapies in newborn and pediatric ICU medicine, including a trial completed out of the University of Pennsylvania as the lead site—the Sustained Aeration of the Infant Lung (SAIL) RCT (Kirpalani H, JAMA 2019; 321:1165-1175). This trial addressed emergent management of the preterm infant who fails to transition to an extrauterine environment at birth. As a delivery room trial of an emergent therapy it faced special challenges of parent information and informed consent. Internationally the climate for the practice of deferred consent for research involving in sick preterm newborns in the delivery room varies a great deal. In the SAIL trial, the data safety and monitoring board (DSMB) noted an unexpected complication of early death within 48 hours of delivery in the experimental arm. The trial was therefore stopped early (426 instead of 600 as planned). Dr. Kirpalani will discuss the SAIL trial, its results, and the discussions that followed. Dr. Chris Feudtner will then comment on the ethical importance of clinical trials of common therapies and the ethics of deferred consent in clinical research.

Haresh Kirpalani, MD, MSc
Emeritus Professor CE of Pediatrics, Perelman School of Medicine

Commentary by Chris Feudtner, MD, PhD, MPH
Director of Research, Pediatric Advanced Care Team, CHOP

SAIL paper: https://jamanetwork.com/journals/jama/fullarticle/2728923 

Dr. David Fajgenbaum will share his groundbreaking work to advance precision medicine for Castleman disease, a condition that he is battling as a physician, researcher, advocate, and patient. Combining -omic technologies with machine learning and other bioinformatic tools, Dr. Fajgenbaum has discovered novel predictive biomarkers of treatment response and novel treatment approaches, including one that is saving his life and others. In this REPS lecture, Dr. Fajgenbaum will discuss the ethics of self-experimentation, fairness of resource allocation across rare diseases, and other ethics and policy issues, reflecting on his own personal journey and research.

David C. Fajgenbaum, MD, MBA, MSc
Assistant Professor of Medicine, Perelman School of Medicine

Nudges are subtle changes to the choice environment that can have an outsized impact on our decisions and behaviors.  Electronic health records have been rapidly adopted by health systems and clinicians, however there exist hidden nudges which are often misaligned with clinician and patient goals. The Penn Medicine Nudge Unit is the world’s first behavioral design team embedded within the operations of a health system and focuses on working with health system leadership and frontline clinicians and staff to design, test, and implement nudges to improve the delivery of health care. This presentation will provide a background on the Penn Medicine Nudge Unit and provide examples of past project and their ethical implications.

Mitesh S. Patel, MD, MBA
Ralph Muller Presidential Associate Professor, Perelman School of Medicine

Dr. Meyer is Associate Professor of Medicine and directs the Center for Translational Lung Biology at Penn. A translational scientist, she and her team pivoted their ongoing sepsis cohort study to enroll moderately and severely ill patients hospitalized with COVID-19 into an observational molecular study that is yielding insights into the varied host immune response incited by SARS-CoV2. She is also involved in several clinical trials for COVID-19 subjects. This lecture will highlight policy decisions and ethical concerns that arose both early in the pandemic, while clinical care was highly uncertain, and issues that persist as the pandemic evolves. Dr. Meyer will attempt to balance the clinician’s perspective as a critical care doctor, the researcher’s desire to maximize and disseminate knowledge, and the administrator’s concerns about justice, transparency, and safety.

Nuala J. Meyer, MD, MS
Associate Professor of Medicine at the Hospital of the University of Pennsylvania
 

In recent years, an increasing number of intraoperative neuroscience studies have been supported by the NIH through the BRAIN initiative. Some of these studies take advantage of intraoperative situations—such as Parkinson’s disease patients undergoing deep brain stimulation surgery—to advance basic neuroscience knowledge. However, the use of neurosurgical patients as human research subjects raises important ethical considerations, particularly regarding informed consent and undue influence, as well as subjects’ motivations for participation. In this talk, I will present results from a recent empirical study that examined these considerations and assessed informed consent recall in Parkinson’s disease patients who participated in an intraoperative neuroscience study at the University of Pennsylvania.

Anna Wexler, PhD
Assistant Professor of Medical Ethics and Health Policy, Perelman School of Medicine
 

The Family Smoking Prevention and Tobacco Control Act, signed into law on June 22, 2009, gives the United States Food and Drug Administration authority to regulate the manufacture, distribution, and marketing of tobacco products. Regulation occurs with a goal of improving the nation’s health, and must be supported by the best and most current scientific evidence and research. In September 2018, the NIH and FDA funded a second round of Tobacco Centers of Regulatory Science (TCORS). Dr. Andrew Strasser is Principal Investigator of the UPenn TCORS, and with colleagues across Penn, Rutgers, Georgetown and Wake Forest Universities, conducts tobacco policy focused research on the advertising, marketing, labeling, use and exposure of combustible tobacco products. He will present his research on nicotine product standards, tobacco advertising, and packaging warning labels that inform tobacco control and regulatory science. 

Andrew A. Strasser, PhD
Research Professor of Psychiatry, Perelman School of Medicine  
 

Research funding bodies in Europe and North America increasingly encourage or require grantees to engage patients not simply as research participants but as partners in all phases of research from topic generation to the dissemination of study results. Patient engagement has been said to improve the relevance, quality, and impact of research, but evidence of these benefits remains limited. This presentation will explore some of the challenges of evaluating the effects of patient engagement in research and also consider the argument that patient engagement in research is intrinsically justified regardless of its effects.

Matthew McCoy, PhD
Assistant Professor, Department of Medical Ethics and Health Policy, Perelman School of Medicine, University of Pennsylvania

 

The most common way for people in the United States to get access to investigational medical products is by participating in clinical trials. For patients who are unable to participate in clinical trials but who wish to try an experimental drug, device, vaccine, or other medical product, there are two pathways that permit non-trial access to products that are still in clinical development and not approved for any use. These are Expanded Access, which has existed for several decades, and Right to Try, which is much newer. Alison Bateman-House will compare and contrast the two pathways and explain why Expanded Access is preferable to Right to Try, both for patients and for the companies whose investigational products will be involved in such “compassionate use” attempts. She will underscore that the existence of such regulatory pathways are necessary but far from sufficient for patients to be able to use experimental medical products outside of clinical trials and highlight what other obstacles, real and perceived, reasonable and unreasonable exist.

Alison Bateman-House, PhD, MPH, MA
Assistant Professor, Division of Medical Ethics
New York University Langone Medical Center
 

Commentary by Robert Vonderheide, MD, DPhil
John H. Glick Abramson Cancer Center Professor, Perelman School of Medicine

The challenges of balancing scientific rigor and ethical concerns in community-engaged research are unique and complex. Ethical issues can arise in terms of methodology, research implementation, and practical aspects of community-based research. This talk will introduce ethical issues related to communities/stakeholders, research participants, and professional relationships with illustrations from case studies and an introduction to useful resources.

Karen Glanz, PhD, MPH
George A. Weiss University Professor
Perelman School of Medicine and School of Nursing



 

Supplemental readings and commentary:

• Reardon, J. The Postgenomic Condition.
• Yudell, M. et al. Taking race out of human genetics.
• Sirugo, G. et al. The missing diversity in human genetic studies.

Sarah Tishkoff, PhD
David and Lyn Silfen University Professor,
Departments of Genetics & Biology, Perelman School of Medicine

Commentary by Kellie Owens, PhD
Fellow, Medical Ethics & Health Policy, Perelman School of Medicine


 

Do you think institutional review boards (IRBs) “work”? What does that mean and how would we know? It turns out that evaluating IRB quality and effectiveness beyond superficial measurements related to compliance and efficiency is remarkably challenging. Nonetheless, it is essential to determining whether the system’s overall benefits outweigh its burdens, as well as what adjustments might be in order. In this lecture, Holly Fernandez Lynch describes the problem and introduces several novel approaches currently being pursued by the Consortium to Advance Effective Research Ethics Oversight (AEREO).

Holly Fernandez Lynch, JD, MBe
John Russell Dickson, MD Presidential Assistant
Professor of Medical Ethics, Medical Ethics & Health Policy, Perelman School of Medicine

 

The controversy about the gene edited babies in China happens to have coincided with increasing tensions between the US and China and intensified competition in the life sciences, including legal action against some Chinese scientists based in the US. In this talk I sketch out the background geopolitical issues that have received little attention but that provide context for the regulation of CRISPR and related technologies.

Jonathan D. Moreno, PhD
David and Lyn Silfen University Professor of Ethics,
Medical Ethics and Health Policy, Perelman School of Medicine




 

Informed consent for clinical research in the context of acute and emergent illness is widely recognized as challenging and is often not possible. There is, however, a wide spectrum of acute and emergent conditions and a similarly wide range of potential for patients and surrogates to engage in decisions about research enrollment. Dr. Dickert will focus on research designed to understand and integrate patients’ and surrogates’ perspectives on consent for clinical trials in the context of acute myocardial infarction and stroke. He will argue that involving patients and surrogates in enrollment decisions in many emergency situations is not pointless despite important limitations that must be recognized.


Neal Dickert, MD, PhD, FACC
Assistant Professor, Emory University School of Medicine
Department of Medicine, Division of Cardiology, ECCRI
Emory University Rollins School of Public Health,
Department of Epidemiology, Emory Center for Ethics

Commentary by Benjamin S. Abella, MD, MPhil, FAHA
Professor and Vice Chair for Research
Director, Center for Resuscitation Science
Department of Emergency Medicine
Perelman School of Medicine

School closure and reopening in light of the COVID-19 pandemic raises critical questions about decision-making in the face of uncertainty, how best to meet the needs of children, how to keep communities safe, and how to generate evidence on each of these issues. In this panel, we’ll hear from leading experts in epidemiology, education, and policy. What do we know about the epidemiology of school opening and closure and what are the most relevant factors to consider? What are the educational impacts of school closure and remote learning and how can negative impacts be minimized? What are the challenges of advising school districts on their responses to the pandemic? Watch this discussion of the ethical implications of each of these questions with Kristen A. Feemster, MD, MPH, MSHPR, FAAP; Jonathan A. Supovitz, EdD, MA; Meredith Matone, DrPH, MHS; and moderated by Holly Fernandez Lynch, JD, MBe. Learn more at improvinghealthcare.net/

In this presentation, Dr. George Yancy argues that whiteness is both an opaque and systemic structure. In short, to be white, to be embodied as white, raises the question not only of white privilege, but the question of white racism and how it is that racism is an insidious phenomenon that is replicated in the lives of white people. We can all agree that white racism is unethical. But what if it is not possible to make a clean exit, as it were, from the bind of whiteness? What if to be white means that one's ethical state, as Peggy McIntosh has suggested, is not completely dependent upon one's ethical will? This raises not only the theme of the unethical structure of whiteness, but the way in which white people (consciously or unconsciously) perpetuate racialized injustice and thereby are unethical.  

George D. Yancy, PhD
Samuel Candler Dobbs Professor of Philosophy, Department of Philosophy, Emory College of Arts and Sciences