title: Spinal Muscular Atrophy Type I: Is It Ethical to Standardize Supportive Care Intervention in Clinical Trials?
abstract: The natural history of spinal muscular atrophy type I (SMA-I) has changed as improved medical support has become available. With investigational drugs for spinal muscular atrophy now in clinical trials, efficient trial design focuses on enrolling recently diagnosed infants, providing best available supportive care, and minimizing subject variation. The quandary has arisen whether it is ethically appropriate to specify a predefined level of nutritional and/or ventilation support for spinal muscular atrophy type I subjects while participating in these studies. We conducted a survey at 2 spinal muscular atrophy investigator meetings involving physician investigators, clinical evaluators, and study coordinators from North America, Europe, and Asia-Pacific. Each group endorsed the concept that having a predefined degree of nutritional and ventilation support was warranted in this context. We discuss how autonomy, beneficence/non-maleficence, noncoercion, social benefit, and equipoise can be maintained when a predefined level of supportive care is proposed, for participation in a clinical trial.
authors.affiliation: 1 Division of Neurology, Nemours Children's Hospital, Orlando, FL, USA.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Finkel
authors.affiliation: 2 Tioga Pharmaceuticals, San Diego, CA, USA.
authors.forename: Kathie M
authors.initials: KM
authors.lastname: Bishop
authors.affiliation: 3 US Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Nelson
mesh_terms: D002986:Clinical Trials as Topic / Q000941:ethics* / Q000592:standards*; D006801:Humans; D007223:Infant; D038622:Internationality; D012107:Research Design; D014897:Spinal Muscular Atrophies of Childhood / Q000628:therapy*
keywords: SMA; Werdnig-Hoffmann disease; clinical trial design; standard of care