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Ethical Issues in Pediatric Gene Therapy Clinical Trials

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Cara Hunt, MA
Lisa Kearns, MS, MA

The Working Group on Pediatric Gene Therapy and Medical Ethics (PGTME) was created in 2019 to study ethical issues surrounding research in genetic interventions for pediatric populations. The group is housed in the Division of Medical Ethics at NYU Grossman School of Medicine and is chaired by Alison Bateman-House, PhD, MPH, MA, assistant professor in the Division of Medical Ethics, and Lesha Shah, MD, assistant professor of psychiatry and the medical director of Child, Adolescent, and Family Services at the Icahn School of Medicine at Mount Sinai. Members comprise experts from the fields of clinical trial design, academia, patient advocacy, drug development, medicine, and law.

The goals of the Center for ELSI Resources and Analysis (CERA) — to enhance knowledge-sharing among multidisciplinary researchers focused on ethical, legal, and social implications of genetics and genomics topics — are reflected in PGTME’s mission: to advance research, policy, and education regarding ethical issues surrounding gene therapy trials and promote improved understanding of challenges and nascent best practices for ethical research across the evolving landscape of genetic technologies. These aims were on display in a weeklong lunchtime conference series that PGTME hosted late last year called Ethical Issues in Pediatric Gene Therapy Clinical Trials, which included discussions of:

  • Risks and Benefits in Pediatric Gene Therapy Research, with Dr. Peter Marks, director of the Center for Biologics Evaluation and Research (CBER) at the FDA, and PGTME members Pat Furlong, founding president and CEO of Parent Project Muscular Dystrophy (PPMD), and Dr. Alison Bateman-House
  • Equity Issues in Pediatric Gene Therapy Research, with Dr. Pilar Ossorio, professor of law and bioethics at University of Wisconsin Law School, and PGTME members Dr. Rafael Escandon, senior vice president of Medical Affairs, Policy, and Patient Engagement at BridgeBio Pharma Inc., and Dr. Aisha Langford, assistant professor at NYU Grossman School of Medicine Department of Population Health
  • Ethical Challenges of Immunogenicity and Toxicity, with Dr. James Wilson, director of the Gene Therapy Program and Orphan Disease Center at the Perelman School of Medicine, and PGTME members Dr. Timothy Cripe, chief of the Division of Hematology and Oncology at Nationwide Children’s Hospital, and Katherine Beaverson, senior director and patient advocacy lead at Pfizer Inc.
  • The Lived Experiences of Patients Participating in Research and their Families, with John Crowley, the father of two children with Pompe disease and the CEO of Amicus Therapeutics, and PGTME members Patrick Moeschen, a high school music teacher and a patient advocate for those with muscular dystrophy, and Dr. Moshe Cohn, pediatric critical care specialist at NYU Langone Hospital
  • Operationalizing Informed Consent in Pediatric Gene Therapy Research, with Dr. Sandy Macrae, CEO and president of Sangamo Therapeutics Inc., and PGTME members Dr. Arthur Caplan, founding director of the NYU Grossman School of Medicine Division of Medical Ethics, and Dr. Lesha Shah

These interdisciplinary conversations reflected a core belief of PGTME’s founders: that without input from all stakeholder groups, it would be impossible to identify the broad range of ethical concerns relevant to the group’s mission, much less propose workable solutions. The conference series also provided an opportunity for attendees to learn more about the challenges young patients and their families face when considering participation in gene therapy clinical research. The series can be seen on the PTGME YouTube channel.

The topics featured in the series were selected based on the results of a landscape survey of pediatric gene therapy research that PGTME has been conducting over the past year to focus the group’s work going forward. This survey entailed listening to a wide variety of stakeholder perspectives. Guest speakers at PGTME’s monthly meetings included a mother of two boys with Duchenne muscular dystrophy and the founder of a rare genetic disease advocacy organization—voices that have been essential to understanding the obstacles that patients and families face and the social dynamics of their interactions with industry, researchers, and clinicians. Other heads of patient advocacy organizations spoke to the group, as did doctors involved with pediatric research and directors of rare disease programs at various children’s hospitals. Members of PGTME also convened two listening sessions—one with patient advocates and another with representatives from gene therapy sponsors—during Rare Disease Week in Washington, D.C., in February 2020.

The lessons learned from the landscape survey, which PGTME hopes to publish in the coming months, inform five areas on which PGTME will focus its research, policy, and education efforts in the coming years:

  • Informed consent, assent, and permission in the context of pediatric gene therapy research trials, for both patients and their surrogate decision makers
  • Viral vector immunity concerns (immunogenicity), specifically with regard to trial design and consequences for the possibility of redosing or future trial participation
  • The lived experience of receiving gene therapy for children and their families
  • Equity in trial recruitment, enrollment, and participation
  • Risk/benefit analyses in the context of pediatric gene therapy clinical trials

Members of PGTME have shared findings throughout the year at various conferences. These include the Columbia Precision Medicine: Ethics, Politics, and Culture series; the ASGCT Policy Summit; the NORD Rare Diseases and Orphan Products Breakthrough Summit; the American Society for Bioethics and Humanities annual meeting; the Oligonucleotide Therapeutics Society; the Orphan Drugs and Rare Diseases Global Congress; the NIH–NCATS/CBER Workshop on Systemic Immunogenicity Considerations for AAV-Mediated Gene Therapy; and others. At these events, our group addressed ethics specifically in the context of research involving pediatric populations. Within this narrow scope, we seek opportunities for collaborative research exploring the ethical and social implications of gene therapy.

PGTME will build on the success of the lunchtime series, its inaugural event, by continuing to host interdisciplinary discussions, hearing from and educating patients and their families, and researching and advising on best practices and policies with regard to trial design, informed consent, equity and accessibility, and patient education. It will share its work broadly with all those interested in the ethics of pediatric gene therapy research.

For more about PGTME and a list of members, visit the group’s website. To receive PGTME’s quarterly newsletter, please email Cara Hunt at [email protected].


The authors thank John Massarelli for his assistance.

Cara Hunt, MA, is a research data associate in the NYU Grossman School of Medicine Division of Medical Ethics and the project manager of PGTME. Lisa Kearns, MS, MA, is senior research associate in the Division of Medical Ethics and a member of PGTME.

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