title: Ethics of placebo-controlled clinical trials in multiple sclerosis: a reassessment.
abstract: The increasing number of established effective therapies for relapsing multiple sclerosis (MS) and emerging consensus for early treatment raise practical concerns and ethical dilemmas for placebo-controlled clinical trials in this disease. An international group of clinicians, ethicists, statisticians, regulators, and representatives from the pharmaceutical industry convened to reconsider prior recommendations regarding the ethics of placebo-controlled trials in MS. The group concluded that placebo-controlled trials can still be done ethically, with restrictions. For patients with relapsing MS for which established effective therapies exist, placebo-controlled trials should only be offered with rigorous informed consent if the subjects refuse to use these treatments, have not responded to them, or if these treatments are not available to them for other reasons (e.g., economics). Suggestions are provided to protect subject autonomy and improve informed consent procedures. Recommendations are tighter than previously suggested for placebo-controlled trials in "resource-restricted" environments where established therapies may not be available. Guidance is also provided on the ethics of alternative trial designs and the balance between study subject burden and risk, scientific rationale and interpretability of trial outcomes.
authors: Department of Neurology, Free University Medical Center in Amsterdam, PO Box 4075, 1007 MB Amsterdam, The Netherlands. ch.polman@vumc.nl
authors: C H
authors: CH
authors: Polman
authors: S C
authors: SC
authors: Reingold
authors: F
authors: F
authors: Barkhof
authors: P A
authors: PA
authors: Calabresi
authors: M
authors: M
authors: Clanet
authors: J A
authors: JA
authors: Cohen
authors: G R
authors: GR
authors: Cutter
authors: M S
authors: MS
authors: Freedman
authors: L
authors: L
authors: Kappos
authors: F D
authors: FD
authors: Lublin
authors: H F
authors: HF
authors: McFarland
authors: L M
authors: LM
authors: Metz
authors: A E
authors: AE
authors: Miller
authors: X
authors: X
authors: Montalban
authors: P W
authors: PW
authors: O'Connor
authors: H
authors: H
authors: Panitch
authors: J R
authors: JR
authors: Richert
authors: J
authors: J
authors: Petkau
authors: S R
authors: SR
authors: Schwid
authors: M P
authors: MP
authors: Sormani
authors: A J
authors: AJ
authors: Thompson
authors: B G
authors: BG
authors: Weinshenker
authors: J S
authors: JS
authors: Wolinsky
mesh_terms: D002986:Clinical Trials as Topic / Q000941:ethics*; D004351:Drug Resistance; D006297:Health Services Accessibility / Q000941:ethics / Q000592:standards; D006801:Humans; D007258:Informed Consent / Q000941:ethics* / Q000592:standards; D016743:Mental Competency / Q000592:standards*; D009103:Multiple Sclerosis / Q000188:drug therapy*; D015990:Placebo Effect; D010919:Placebos / Q000592:standards*; D018570:Risk Assessment / Q000941:ethics; D016896:Treatment Outcome
chemical_list: D010919:Placebos