title: Confronting the issues of therapeutic misconception, enrollment decisions, and personal motives in genetic medicine-based clinical research studies for fatal disorders.
abstract: Genetic medicine-based therapies have unlocked the potential for ameliorating diseases previously considered inevitably fatal. Inherent in the clinical trials of genetic medicines are ethical issues of therapeutic misconception, enrollment decisions as they relate to the risks and benefits of research, and the complex relationships among funding sources, investigators, and the families of affected individuals. The purpose of this paper is to help define these complex issues relevant to the use of genetic medicines and to describe the strategy we have used to confront these issues in a phase I trial of adeno-associated virus-mediated gene transfer to the central nervous system of children with late infantile neuronal ceroid lipofuscinosis (LINCL), a fatal lysosomal storage disease associated with progressive neurodegeneration and death by mid-childhood. Our approach to these challenges should provide a useful paradigm for investigators initiating other genetic medicine- based studies to treat inevitably fatal diseases.
authors.affiliation: Department of Genetic Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Arkin
authors.forename: Dolan
authors.initials: D
authors.lastname: Sondhi
authors.forename: Stefan
authors.initials: S
authors.lastname: Worgall
authors.forename: Lily Hyon K
authors.initials: LH
authors.lastname: Suh
authors.forename: Neil R
authors.initials: NR
authors.lastname: Hackett
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Kaminsky
authors.forename: Syed A
authors.initials: SA
authors.lastname: Hosain
authors.forename: Mark M
authors.initials: MM
authors.lastname: Souweidane
authors.forename: Michael G
authors.initials: MG
authors.lastname: Kaplitt
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Dyke
authors.forename: Linda A
authors.initials: LA
authors.lastname: Heier
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Ballon
authors.forename: Dikoma C
authors.initials: DC
authors.lastname: Shungu
authors.forename: Krystyna E
authors.initials: KE
authors.lastname: Wisniewski
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Greenwald
authors.forename: Charleen
authors.initials: C
authors.lastname: Hollmann
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
mesh_terms: D017321:Clinical Trials, Phase I as Topic / Q000941:ethics / Q000639:trends; D015316:Genetic Therapy / Q000941:ethics / Q000379:methods; D006801:Humans; D009042:Motivation; D009472:Neuronal Ceroid-Lipofuscinoses / Q000628:therapy*; D010342:Patient Acceptance of Health Care; D018579:Patient Selection / Q000941:ethics*; D018570:Risk Assessment