Ethics of placebo-controlled clinical trials in multiple sclerosis: a reassessment

• Published in: Neurology Vol. 70; no. 13 Pt 2; pp. 1134 - 1140
• Main Authors: Polman, C H, Reingold, S C, Barkhof, F, Calabresi, P A, Clanet, M, Cohen, J A, Cutter, G R, Freedman, M S, Kappos, L, Lublin, F D, McFarland, H F, Metz, L M, Miller, A E, Montalban, X, O'Connor, P W, Panitch, H, Richert, J R, Petkau, J, Schwid, S R, Sormani, M P, Thompson, A J, Weinshenker, B G, Wolinsky, J S
• Format: Journal Article Conference Proceeding
• Language: English
• Published: United States 25-03-2008
• Subjects: Clinical Trials as Topic - ethics; Drug Resistance; Health Services Accessibility - ethics; Health Services Accessibility - standards; Humans; Informed Consent - ethics; Informed Consent - standards; Mental Competency - standards; Multiple Sclerosis - drug therapy; Placebo Effect; Placebos - standards; Risk Assessment - ethics; Treatment Outcome
• ISSN: 0028-3878; 1526-632X
• DOI: 10.1212/01.wnl.0000306410.84794.4d

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.