title: Pragmatic randomized trials in drug development pose new ethical questions: a systematic review.
abstract: Implementation of pragmatic design elements in drug development could bridge the evidence gap that currently exists between the knowledge we have regarding the efficacy of a drug versus its true, comparative effectiveness in real life. We performed a review of the literature to identify the ethical challenges thus far related to pragmatic trials. The three central ethical questions identified for pragmatic trials are: (i) what level of oversight should pragmatic trials require; (ii) do randomized patients face additional risks; and (iii) is a waiver of informed consent ethically defensible? Despite the fact all reviewed publications dealt with post-launch pragmatic trials, these results could serve as an important starting point for conceptualizing which challenges could potentially arise in the pre-launch setting.
authors: Department of Medical Humanities, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, PO Box 85500, 3508 GA Utrecht, The Netherlands. Electronic address: s.kalkman@umcutrecht.nl.
authors: Shona
authors: S
authors: Kalkman
authors: Department of Medical Humanities, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, PO Box 85500, 3508 GA Utrecht, The Netherlands.
authors: Ghislaine J M W
authors: GJ
authors: van Thiel
authors: Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, PO Box 85500, 3508 GA Utrecht, The Netherlands.
authors: Diederick E
authors: DE
authors: Grobbee
authors: Department of Medical Humanities, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, PO Box 85500, 3508 GA Utrecht, The Netherlands.
authors: Johannes J M
authors: JJ
authors: van Delden
mesh_terms: D055808:Drug Discovery / Q000941:ethics*; D006801:Humans; D007258:Informed Consent / Q000941:ethics; D061214:Patient Safety; D064792:Pragmatic Clinical Trials as Topic / Q000941:ethics*; D012107:Research Design; D035842:Research Subjects; D018570:Risk Assessment; D012307:Risk Factors