title: Decline in placebo-controlled trial results suggests new directions for comparative effectiveness research.
abstract: The Affordable Care Act offers strong support for comparative effectiveness research, which entails comparisons among active treatments, to provide the foundation for evidence-based practice. Traditionally, a key form of research into the effectiveness of therapeutic treatments has been placebo-controlled trials, in which a specified treatment is compared to placebo. These trials feature high-contrast comparisons between treatments. Historical trends in placebo-controlled trials have been evaluated to help guide the comparative effectiveness research agenda. We investigated placebo-controlled trials reported in four leading medical journals between 1966 and 2010. We found that there was a significant decline in average effect size or average difference in efficacy (the ability to produce a desired effect) between the active treatment and placebo. On average, recently studied treatments offered only small benefits in efficacy over placebo. A decline in effect sizes in conventional placebo-controlled trials supports an increased emphasis on other avenues of research, including comparative studies on the safety, tolerability, and cost of treatments with established efficacy.
authors.affiliation: Columbia University, New York, NY, USA. mo49@columbia.edu
authors.forename: Mark
authors.initials: M
authors.lastname: Olfson
authors.forename: Steven C
authors.initials: SC
authors.lastname: Marcus
mesh_terms: D057186:Comparative Effectiveness Research / Q000331:legislation & jurisprudence / Q000379:methods* / Q000639:trends; D018849:Controlled Clinical Trials as Topic / Q000379:methods* / Q000639:trends; D016206:Databases, Bibliographic; D006801:Humans; D058991:Patient Protection and Affordable Care Act / Q000592:standards; D010919:Placebos; D014481:United States
chemical_list: D010919:Placebos
keywords: Evidence-Based Medicine; Health Reform; Research And Technology